{"id": "PMID:152800", "title": "Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens.", "content": "We have studied the modulation of Ia-like antigens on the surface membrane of human T cells responding in a one-way mixed leukocyte culture. A heterologous antiserum, (anti-p23,30), which is specific to HLA-D-related antigens and which is unreactive with normal peripheral T cells or thymocytes, was found to bind significantly to all T cells transformed in mixed leukocyte culture (MLC) as determined by indirect immunofluorescence on a fluorescence-activated cell sorter 1. Furthermore, cytotoxic T cells responsible for cell-mediated lympholysis were shown to react with anti-p23,30, whereas their unactivated progenitors did not. Immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis of a radioactive 29,000 and 34,000 dalton complex from MLC-primed T cells labeled with [35S]methionine indicated that allosensitized T cells synthesized these HLA-D-related antigens.", "contents": "Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens. We have studied the modulation of Ia-like antigens on the surface membrane of human T cells responding in a one-way mixed leukocyte culture. A heterologous antiserum, (anti-p23,30), which is specific to HLA-D-related antigens and which is unreactive with normal peripheral T cells or thymocytes, was found to bind significantly to all T cells transformed in mixed leukocyte culture (MLC) as determined by indirect immunofluorescence on a fluorescence-activated cell sorter 1. Furthermore, cytotoxic T cells responsible for cell-mediated lympholysis were shown to react with anti-p23,30, whereas their unactivated progenitors did not. Immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis of a radioactive 29,000 and 34,000 dalton complex from MLC-primed T cells labeled with [35S]methionine indicated that allosensitized T cells synthesized these HLA-D-related antigens."} {"id": "PMID:152801", "title": "Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses.", "content": "Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function.", "contents": "Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses. Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function."} {"id": "PMID:152799", "title": "The disturbance of oxidative phosphorylation in rat liver mitochondria by the carcinogens 12-hydroxystearic acid and its methyl ester.", "content": "In a search to determine common molecular features in potential carcinogenic dietary fatty acids, Swern et al. (1970) found that 12-hydroxystearic acid and its methyl ester were carcinogenic. This was surprising to Swern et al. (1970) and Van Duuren et al. (1972), as it was not readily apparent how such agents could be converted to alkylating agents. We have observed that the carcinogens 12-hydroxystearic acid and its methyl ester disrupted oxidative phosphorylation in rat liver mitochondria. The in vitro mitochondrial effects induced by the agents included: a) uncoupled respiration, b) ATPase activity, c) energized volume changes linked either to respiration or ATP. Mitochondria mediated the enzymic conversion of the ester to the acid. Conversion was retarded by the thiol reagent showdomycin. These data in conjuction with our previous reports dealing with other carcinogens and their derivatives contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis.", "contents": "The disturbance of oxidative phosphorylation in rat liver mitochondria by the carcinogens 12-hydroxystearic acid and its methyl ester. In a search to determine common molecular features in potential carcinogenic dietary fatty acids, Swern et al. (1970) found that 12-hydroxystearic acid and its methyl ester were carcinogenic. This was surprising to Swern et al. (1970) and Van Duuren et al. (1972), as it was not readily apparent how such agents could be converted to alkylating agents. We have observed that the carcinogens 12-hydroxystearic acid and its methyl ester disrupted oxidative phosphorylation in rat liver mitochondria. The in vitro mitochondrial effects induced by the agents included: a) uncoupled respiration, b) ATPase activity, c) energized volume changes linked either to respiration or ATP. Mitochondria mediated the enzymic conversion of the ester to the acid. Conversion was retarded by the thiol reagent showdomycin. These data in conjuction with our previous reports dealing with other carcinogens and their derivatives contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis."} {"id": "PMID:152802", "title": "Host antigen as the sulphated moiety of influenza virus haemagglutinin.", "content": "Inorganic sulphate (35S) was incorporated into the haemagglutinin molecule of A/Memphis/1/71 (H3N2) influenza virus when a keratosulphate-like host antigen was also incorporated into the glycoproteins of virus grown in the chorioallantoic membrane of the embryonated hen's egg. Little or no 35S-sulphate was incorporated when this hose antigen was not present in the glycoproteins of virus grown in chick embryo kidney cells or in the chorioallantoic membrane of embryonated duck eggs. The presence of the keratosulphate-like host antigen was required for the stability of the haemagglutinin molecule in sodium dodecyl sulphate (SDS). The haemagglutinin molecules from virus grown in hens' eggs were stable in SDS, whereas those from virus grown in duck eggs or in chick embryo kidney cells were not and could not be isolated on cellulose acetate. Chemical analysis showed that there were 87 glucosamine residues and three molecules of sulphate per haemagglutinin subunit as calculated for a trimer molecule having a mol. wt. of 200 000. There was one sulphate molecule per HA1 polypeptide chain and this was associated with the slowest migrating carbohydrate-protein complex of an HA1 tryptic digest separated by polyacrylamide gel electrophoresis.", "contents": "Host antigen as the sulphated moiety of influenza virus haemagglutinin. Inorganic sulphate (35S) was incorporated into the haemagglutinin molecule of A/Memphis/1/71 (H3N2) influenza virus when a keratosulphate-like host antigen was also incorporated into the glycoproteins of virus grown in the chorioallantoic membrane of the embryonated hen's egg. Little or no 35S-sulphate was incorporated when this hose antigen was not present in the glycoproteins of virus grown in chick embryo kidney cells or in the chorioallantoic membrane of embryonated duck eggs. The presence of the keratosulphate-like host antigen was required for the stability of the haemagglutinin molecule in sodium dodecyl sulphate (SDS). The haemagglutinin molecules from virus grown in hens' eggs were stable in SDS, whereas those from virus grown in duck eggs or in chick embryo kidney cells were not and could not be isolated on cellulose acetate. Chemical analysis showed that there were 87 glucosamine residues and three molecules of sulphate per haemagglutinin subunit as calculated for a trimer molecule having a mol. wt. of 200 000. There was one sulphate molecule per HA1 polypeptide chain and this was associated with the slowest migrating carbohydrate-protein complex of an HA1 tryptic digest separated by polyacrylamide gel electrophoresis."} {"id": "PMID:152803", "title": "The effect of a high level of dietary leucine on the niacin status of dogs.", "content": "Two feeding trials were designed to precipitate niacin deficiency in puppies receiving low levels of niacin by adding 15 g/kg supplementary l-leucine to a diet containing 180 g/kg casein. We failed to produce such an effect and, as niacin levels were gradually reduced, the times at which control dogs became deficient (and then responded to injections of the vitamin) were not significantly different from those for dogs receiving the leucine supplement. Differences between the conditions of our experiments and of the experiment in which this effect was found are discussed. Two pairs of littermates in trial 2 died suddenly while apparently in fairly good condition, but revealing fatty livers and/or changes in heart muscle on autopsy. Similar observations have been reported by others using purified diets with dogs over long periods; there is no certain explanation.", "contents": "The effect of a high level of dietary leucine on the niacin status of dogs. Two feeding trials were designed to precipitate niacin deficiency in puppies receiving low levels of niacin by adding 15 g/kg supplementary l-leucine to a diet containing 180 g/kg casein. We failed to produce such an effect and, as niacin levels were gradually reduced, the times at which control dogs became deficient (and then responded to injections of the vitamin) were not significantly different from those for dogs receiving the leucine supplement. Differences between the conditions of our experiments and of the experiment in which this effect was found are discussed. Two pairs of littermates in trial 2 died suddenly while apparently in fairly good condition, but revealing fatty livers and/or changes in heart muscle on autopsy. Similar observations have been reported by others using purified diets with dogs over long periods; there is no certain explanation."} {"id": "PMID:152804", "title": "Early effects of vitamin A toxicity on hepatic glycolysis in rat.", "content": "Vitamin A toxicity, caused by oral administration of 30,000 IU of vitamin A (retinyl palmitate) to young rats (70 to 90 g) once daily for 2 days, increased the levels of lipids, glycogen, and citrate in the liver. Furthermore, hypervitaminosis A decreased the activities of two key hepatic glycolytic enzymes, phosphofructokinase, and pyruvate kinase, without affecting those of hexokinase and glucokinase. It is suggested, therefore, that in addition to the increased activities of key gluconeogenic enzymes, reported earlier, a marked decrease in the activities of phosphofructokinase and pyruvate kinase and elevated level of citrate in the liver could account for the enhanced gluconeogenesis in hypervitaminosis A.", "contents": "Early effects of vitamin A toxicity on hepatic glycolysis in rat. Vitamin A toxicity, caused by oral administration of 30,000 IU of vitamin A (retinyl palmitate) to young rats (70 to 90 g) once daily for 2 days, increased the levels of lipids, glycogen, and citrate in the liver. Furthermore, hypervitaminosis A decreased the activities of two key hepatic glycolytic enzymes, phosphofructokinase, and pyruvate kinase, without affecting those of hexokinase and glucokinase. It is suggested, therefore, that in addition to the increased activities of key gluconeogenic enzymes, reported earlier, a marked decrease in the activities of phosphofructokinase and pyruvate kinase and elevated level of citrate in the liver could account for the enhanced gluconeogenesis in hypervitaminosis A."} {"id": "PMID:152805", "title": "Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications.", "content": "PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed.", "contents": "Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications. PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed."} {"id": "PMID:152806", "title": "Ultrastructure of the skin of patients treated with sodium aurothiomalate.", "content": "Skin biopsies from cases of rheumatoid arthritis treated with sodium aurothiomalate were examined with the electron microscope. Intralysosomal gold deposits were found in the macrophages of both normal-looking skin and from areas of erythematous rash that had developed as a toxic manifestation of gold therapy. The main difference between affected and normal-looking skin was the presence of numerous mast cells in the former. It is hence suggested that the dermatologic side-effects of gold are probably mediated by the release of vasoactive substances from mast cells and that vigorous administration of antihistamines to neutralise the liberated products of mast cells or an agent that interferes with degranulation of mast cells might have a palliative effect on the skin rash that sometimes develops during chrysotherapy.", "contents": "Ultrastructure of the skin of patients treated with sodium aurothiomalate. Skin biopsies from cases of rheumatoid arthritis treated with sodium aurothiomalate were examined with the electron microscope. Intralysosomal gold deposits were found in the macrophages of both normal-looking skin and from areas of erythematous rash that had developed as a toxic manifestation of gold therapy. The main difference between affected and normal-looking skin was the presence of numerous mast cells in the former. It is hence suggested that the dermatologic side-effects of gold are probably mediated by the release of vasoactive substances from mast cells and that vigorous administration of antihistamines to neutralise the liberated products of mast cells or an agent that interferes with degranulation of mast cells might have a palliative effect on the skin rash that sometimes develops during chrysotherapy."} {"id": "PMID:152807", "title": "Prolactin in umbilical cord blood and the respiratory distress syndrome.", "content": "Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.", "contents": "Prolactin in umbilical cord blood and the respiratory distress syndrome. Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation."} {"id": "PMID:152808", "title": "Hypomorphic variant of C3, arthritis, and chronic glomerulonephritis.", "content": "Decreased synthesis (hypomorphism) of the fast variant of the third component of complement was detected in three generations of a family in which the propositus has an immune complex-type glomerulonephritis, arthritis, and a false positive test for syphilis. An affected sibling has bursitis, hematuria, and proteinuria. Decreased serum C3 protein was detected in three of four and decreased C3H50 in four of four family members with this hypomorphic variant (C3f). This is the first association between C3f and immune complex-type disease.", "contents": "Hypomorphic variant of C3, arthritis, and chronic glomerulonephritis. Decreased synthesis (hypomorphism) of the fast variant of the third component of complement was detected in three generations of a family in which the propositus has an immune complex-type glomerulonephritis, arthritis, and a false positive test for syphilis. An affected sibling has bursitis, hematuria, and proteinuria. Decreased serum C3 protein was detected in three of four and decreased C3H50 in four of four family members with this hypomorphic variant (C3f). This is the first association between C3f and immune complex-type disease."} {"id": "PMID:152810", "title": "Histological analysis of cat muscle spindles following direct observation of the effects of stimulating dynamic and static motor axons.", "content": "1. Eleven cat tenuissimus spindles have been analysed mainly by cutting serial, transverse, 1 micrometer thick sections following direct observation of the effects of dynamic motor (gamma or beta) stimulation. 2. Histological results from these spindles were also used to interpret the effects of static fusimotor stimulation of other spindles. 3. Dynamic motor stimulation usually produced contractions seen as convergent movements of sarcomeres in single bag fibres, identified as bag1 fibres for reasons given in the text. 4. In one spindle a single dynamic axon produced a translational movement in one pole of a bag1 fibre and a convergent movement in each pole of a bag2 fibre, together with movements in other unidentified (presumably chain) fibres. Subsequent analysis showed that besides innervating both bag fibres the axon also supplied two chain fibres. 5. Contrary to expectation, motor endings on the bag1 fibres seldom occurred at the sites of convergent movement. Only two cases of coincidence occurred among sixteen foci and twenty-one motor endings; otherwise focus and nearest ending were separated by distances of 0.85--2.5 mm. 6. Most of the convergent movements of sarcomeres observed in bag1 fibres occurred in a region of the pole that is ultrastructurally distinct from the region where most of the motor endings were located. The possible relevance of this to the production of contractions in the bag1 fibre is discussed. 7. Convergent movement foci in bag2 fibres produced by the stimulation of static axons occurred largely within the same regions of the pole as the motor endings were located, though, whereas foci were observed in both intra- and extracapsular regions, most of the endings were intracapsular.", "contents": "Histological analysis of cat muscle spindles following direct observation of the effects of stimulating dynamic and static motor axons. 1. Eleven cat tenuissimus spindles have been analysed mainly by cutting serial, transverse, 1 micrometer thick sections following direct observation of the effects of dynamic motor (gamma or beta) stimulation. 2. Histological results from these spindles were also used to interpret the effects of static fusimotor stimulation of other spindles. 3. Dynamic motor stimulation usually produced contractions seen as convergent movements of sarcomeres in single bag fibres, identified as bag1 fibres for reasons given in the text. 4. In one spindle a single dynamic axon produced a translational movement in one pole of a bag1 fibre and a convergent movement in each pole of a bag2 fibre, together with movements in other unidentified (presumably chain) fibres. Subsequent analysis showed that besides innervating both bag fibres the axon also supplied two chain fibres. 5. Contrary to expectation, motor endings on the bag1 fibres seldom occurred at the sites of convergent movement. Only two cases of coincidence occurred among sixteen foci and twenty-one motor endings; otherwise focus and nearest ending were separated by distances of 0.85--2.5 mm. 6. Most of the convergent movements of sarcomeres observed in bag1 fibres occurred in a region of the pole that is ultrastructurally distinct from the region where most of the motor endings were located. The possible relevance of this to the production of contractions in the bag1 fibre is discussed. 7. Convergent movement foci in bag2 fibres produced by the stimulation of static axons occurred largely within the same regions of the pole as the motor endings were located, though, whereas foci were observed in both intra- and extracapsular regions, most of the endings were intracapsular."} {"id": "PMID:152812", "title": "Inhibition of four human serine proteases by substituted benzamidines.", "content": "A series of substituted benzamidines has been examined for their inhibitory activity against the human serine proteases--trypsin, thrombin, plasmin, and C1s, a subunit of the first component of complement. The inhibition constants obtained for each enzyme were correlated with physical-chemical properties of the substituent group using the quantitative structure-activity relationship approach. This analysis indicated that plasmin and C1s are very similar in their interactions with substituted benzamidines. The binding of benzamidines in both enzymes was affected by electron donation from the substituent and its hydrophobicity. Thrombin-benzamidine interaction was affected only by the hydrophobicity of the substituent. Trypsin displayed a complex interaction with substituted benzamidines, and interaction was dependent on molar refractivity and molecular weight. Certain substituents deviated significantly from the interactions predicted by the analysis. These compounds, the (m- and p-amidinophenyl)pyruvic acids, when analyzed by computer modeling, suggested that direct interaction between the substituent and the enzyme surface is important in assessing the effect of substituent groups on inhibitory activity.", "contents": "Inhibition of four human serine proteases by substituted benzamidines. A series of substituted benzamidines has been examined for their inhibitory activity against the human serine proteases--trypsin, thrombin, plasmin, and C1s, a subunit of the first component of complement. The inhibition constants obtained for each enzyme were correlated with physical-chemical properties of the substituent group using the quantitative structure-activity relationship approach. This analysis indicated that plasmin and C1s are very similar in their interactions with substituted benzamidines. The binding of benzamidines in both enzymes was affected by electron donation from the substituent and its hydrophobicity. Thrombin-benzamidine interaction was affected only by the hydrophobicity of the substituent. Trypsin displayed a complex interaction with substituted benzamidines, and interaction was dependent on molar refractivity and molecular weight. Certain substituents deviated significantly from the interactions predicted by the analysis. These compounds, the (m- and p-amidinophenyl)pyruvic acids, when analyzed by computer modeling, suggested that direct interaction between the substituent and the enzyme surface is important in assessing the effect of substituent groups on inhibitory activity."} {"id": "PMID:152813", "title": "Trichloroacetamidines, a new class of positive inotropic agents.", "content": "A series of trichloroacetamidine derivatives, obtained by addition of amines to trichloroacetonitrile, was evaluated for positive inotropic activity on isolated cat heart papillary muscles. Increased contractility, not antagonized by beta-adrenergic blockade with sotalol or reserpine pretreatment, was observed in this assay with a variety of N-substituted trichloroacetamidine derivatives. More extensive pharmacological studies with the 3-indolylmethyl analogue 2 showed that this amidine in dogs, 5 mg/kg iv, produced a positive inotropic effect more pronounced than that of ouabain, 50 microgram/kg iv. Several of the trichloroacetamidines were found to be inhibitors of guinea pig kidney and calf heart Na-K-dependent ATPase and to have specificity for these enzymes different from that of ouabain. Bacterial mutagenic activity was observed with three members, 2,3, and 12, of the series.", "contents": "Trichloroacetamidines, a new class of positive inotropic agents. A series of trichloroacetamidine derivatives, obtained by addition of amines to trichloroacetonitrile, was evaluated for positive inotropic activity on isolated cat heart papillary muscles. Increased contractility, not antagonized by beta-adrenergic blockade with sotalol or reserpine pretreatment, was observed in this assay with a variety of N-substituted trichloroacetamidine derivatives. More extensive pharmacological studies with the 3-indolylmethyl analogue 2 showed that this amidine in dogs, 5 mg/kg iv, produced a positive inotropic effect more pronounced than that of ouabain, 50 microgram/kg iv. Several of the trichloroacetamidines were found to be inhibitors of guinea pig kidney and calf heart Na-K-dependent ATPase and to have specificity for these enzymes different from that of ouabain. Bacterial mutagenic activity was observed with three members, 2,3, and 12, of the series."} {"id": "PMID:152820", "title": "The absence of back pain in classical ankylosing spondylitis.", "content": "Despite the early description of painless spinal ankylosis, the existence of a clinical subset of ankylosing spondylitis with silent axial disease has largely been overlooked. Of 45 patients who met Rome diagnostic criteria for ankylosing spondylitis, five denied ever having back pain either as an initial symptom or during the subsequent course of their illness. All had decreased lumbar spine motion and bilateral radiographic sacroiliitis of at least grade III severity. Chest expansion was decreased in four, and radiographic involvement of the cervical and lumbar spine was observed in three and two patients, respectively. There were no differences observed in sex or race distribution, or frequencies of peripheral arthritis, heel pain, acute uveitis, genito-urinary infection or HLA-B27 positivity when these patients were compared with the remaining patients with back pain. These patients support the existence of a \"latent\" form of ankylosing spondylitis with silent axial disease.", "contents": "The absence of back pain in classical ankylosing spondylitis. Despite the early description of painless spinal ankylosis, the existence of a clinical subset of ankylosing spondylitis with silent axial disease has largely been overlooked. Of 45 patients who met Rome diagnostic criteria for ankylosing spondylitis, five denied ever having back pain either as an initial symptom or during the subsequent course of their illness. All had decreased lumbar spine motion and bilateral radiographic sacroiliitis of at least grade III severity. Chest expansion was decreased in four, and radiographic involvement of the cervical and lumbar spine was observed in three and two patients, respectively. There were no differences observed in sex or race distribution, or frequencies of peripheral arthritis, heel pain, acute uveitis, genito-urinary infection or HLA-B27 positivity when these patients were compared with the remaining patients with back pain. These patients support the existence of a \"latent\" form of ankylosing spondylitis with silent axial disease."} {"id": "PMID:152824", "title": "Evidence of phospholipids and mucopolysaccharides in the cystic fluid from a patient with generalized tissue calcification.", "content": "Analyses of the cystic fluid from a patient with massive tissue calcification showed a significant amount of acid mucopolysaccharides (mainly hyaluronic acid) and phospholipid-polypeptide complexes. The possible role of those molecules in this type of calcinosis is discussed.", "contents": "Evidence of phospholipids and mucopolysaccharides in the cystic fluid from a patient with generalized tissue calcification. Analyses of the cystic fluid from a patient with massive tissue calcification showed a significant amount of acid mucopolysaccharides (mainly hyaluronic acid) and phospholipid-polypeptide complexes. The possible role of those molecules in this type of calcinosis is discussed."} {"id": "PMID:152826", "title": "The occurrence in mice of facial and mandibular abscesses associated with Staphylococcus aureus.", "content": "Swellings affecting the face and jaws of a strain of outbred BSVS mice are described. The swellings consisted of multiple abscesses which were most commonly associated with the mandible. Staphylococcus aureus of a single phage type was isolated from the abscesses. It is suggested that the organisms gained entry through the oral mucosa.", "contents": "The occurrence in mice of facial and mandibular abscesses associated with Staphylococcus aureus. Swellings affecting the face and jaws of a strain of outbred BSVS mice are described. The swellings consisted of multiple abscesses which were most commonly associated with the mandible. Staphylococcus aureus of a single phage type was isolated from the abscesses. It is suggested that the organisms gained entry through the oral mucosa."} {"id": "PMID:152828", "title": "[Solar acne].", "content": "Acne solaris a form of acne that appears and relapses after sun exposure, is almost always itchy and is preferably localized on the upper anterior chest, the deltoid regions and the shoulders. The use of greasy or oily sun protectors helps in the obstructions of the follicular openings, which is seen in the tissue sections, presumably initiated by sun irradiation causing initially hyperkeratosis. The essential lesion is a small hemispheric or conic erythematous papule which may show a yellow point in its top. True comedos are not seen and compression after punction provokes the appearance of a yellow mass-essentially keratinic and sebaceous. The usual treatment of acne vulgaris is useful specially if a topical corticosteroid is associated. The systemic use of corticosteroids usually worsens the disease.", "contents": "[Solar acne]. Acne solaris a form of acne that appears and relapses after sun exposure, is almost always itchy and is preferably localized on the upper anterior chest, the deltoid regions and the shoulders. The use of greasy or oily sun protectors helps in the obstructions of the follicular openings, which is seen in the tissue sections, presumably initiated by sun irradiation causing initially hyperkeratosis. The essential lesion is a small hemispheric or conic erythematous papule which may show a yellow point in its top. True comedos are not seen and compression after punction provokes the appearance of a yellow mass-essentially keratinic and sebaceous. The usual treatment of acne vulgaris is useful specially if a topical corticosteroid is associated. The systemic use of corticosteroids usually worsens the disease."} {"id": "PMID:152829", "title": "[The nitro-blue-tetrazolium test in acne vulgaris (9-12-77)].", "content": "41 patients with different AV stages were studied with the quantitative NAT test. In those cases where there was an inflammatory process (stages III and IV) it was positive, while in was negative. The authors consider the relation between this test and the positive Lymphoblastic Transformation Test to PA, which makes evident a coordinate action of the immune specific system and the granulocytic one. This facts show that AV at the inflammatory stage is an immunologic systemic process and not only a local one.", "contents": "[The nitro-blue-tetrazolium test in acne vulgaris (9-12-77)]. 41 patients with different AV stages were studied with the quantitative NAT test. In those cases where there was an inflammatory process (stages III and IV) it was positive, while in was negative. The authors consider the relation between this test and the positive Lymphoblastic Transformation Test to PA, which makes evident a coordinate action of the immune specific system and the granulocytic one. This facts show that AV at the inflammatory stage is an immunologic systemic process and not only a local one."} {"id": "PMID:152833", "title": "[A cyst of the spleen in a patient with schistosomiasis. Its detection by laparoscopy (author's transl)].", "content": "The authors report the observation of a 23 years old man, who presented an urinary schistosomiasis (S. haematobium) and an intestinal schistosomiasis (S. mansoni). Important abdominal pains, and an enormous splenomegaly compressing stomach and colon, lead to a laparoscopy, which gave evidence of a big liquid cyst of the spleen. Its exeresis brought recovery.", "contents": "[A cyst of the spleen in a patient with schistosomiasis. Its detection by laparoscopy (author's transl)]. The authors report the observation of a 23 years old man, who presented an urinary schistosomiasis (S. haematobium) and an intestinal schistosomiasis (S. mansoni). Important abdominal pains, and an enormous splenomegaly compressing stomach and colon, lead to a laparoscopy, which gave evidence of a big liquid cyst of the spleen. Its exeresis brought recovery."} {"id": "PMID:152869", "title": "The ratio of de novo unbalanced translocation to 47, trisomy 21 Down syndrome. A new method for human mutation surveillance and an apparent recent change in mutation rate resulting in human interchange trisomies in one jurisdiction.", "content": "The Down syndrome phenotype may be associated with, among other genotypes, an unbalanced Robertsonian translocation producing an \"interchange trisomy\" with 46 chromosomes, or 47, trisomy 21. Translocations, like specificlocus point mutations, result from a direct change in structural chromosome elements. In contrast 47, trisomy 21 results from meiotic non-disjunction. Mutation rates for interchange trisomies may be followed indirectly by determining the ratio of instances of Down syndrome associated with a new translocation mutation to those produced by 47, trisomy 21, which accounts for the bulk of the Down syndrome phenotype. This genotypic ratio can be analyzed in data from cytogenetic laboratories, clinics, and chromosome registries and does not depend upon intensive chromosome screening of newborn populations. A similar approach can be adopted to follow trends in Patau syndrome. The genotypic ratio, stratified by maternal age, may in addition, provide a sentinel index for changes in human specific-locus mutations and perhaps other adverse health consequences. Analysis of data from the New York State-North-eastern chromosome registry revealed a two- to three-fold increase in the genotypic ratio for both Down syndrome and Patau syndrome for individuals born in 1973, 1974 and 1975 compared to those born in earlier years.", "contents": "The ratio of de novo unbalanced translocation to 47, trisomy 21 Down syndrome. A new method for human mutation surveillance and an apparent recent change in mutation rate resulting in human interchange trisomies in one jurisdiction. The Down syndrome phenotype may be associated with, among other genotypes, an unbalanced Robertsonian translocation producing an \"interchange trisomy\" with 46 chromosomes, or 47, trisomy 21. Translocations, like specificlocus point mutations, result from a direct change in structural chromosome elements. In contrast 47, trisomy 21 results from meiotic non-disjunction. Mutation rates for interchange trisomies may be followed indirectly by determining the ratio of instances of Down syndrome associated with a new translocation mutation to those produced by 47, trisomy 21, which accounts for the bulk of the Down syndrome phenotype. This genotypic ratio can be analyzed in data from cytogenetic laboratories, clinics, and chromosome registries and does not depend upon intensive chromosome screening of newborn populations. A similar approach can be adopted to follow trends in Patau syndrome. The genotypic ratio, stratified by maternal age, may in addition, provide a sentinel index for changes in human specific-locus mutations and perhaps other adverse health consequences. Analysis of data from the New York State-North-eastern chromosome registry revealed a two- to three-fold increase in the genotypic ratio for both Down syndrome and Patau syndrome for individuals born in 1973, 1974 and 1975 compared to those born in earlier years."} {"id": "PMID:152870", "title": "Cilia with defective radial spokes: a cause of human respiratory disease.", "content": "We studied the fine structure of respiratory-tract cilia in three siblings with chronic respiratory disease, comparing them with those from a patient with Kartagener's syndrome who had dynein-deficient cilia and with control patients who had chronic bronchitis or chronic sinusitis. Electron microscopy of the siblings revealed a new abnormality in the ciliary axoneme--namely, lack of the radial spokes. Their cilia showed an eccentric central pair of tubules but otherwise had a normal central sheath, outer-doublet microtubules, nexin links and dynein arms. The cilia were immotile. Mucociliary clearance was completely lacking in the three siblings and in the patient with Kartagener's syndrome, but was normal in their parents and unaffected siblings. Sperm from the male sibling showed identical structural abnormalities and were immotile. We consider the radial spoke defect to be the congenital anomaly responsible for dysfunction of the mucociliary clearance mechanism in these three patients and of the immotile sperm in one of the them. This defect is apparently another cause of the \"immotilecilia syndrome.\"", "contents": "Cilia with defective radial spokes: a cause of human respiratory disease. We studied the fine structure of respiratory-tract cilia in three siblings with chronic respiratory disease, comparing them with those from a patient with Kartagener's syndrome who had dynein-deficient cilia and with control patients who had chronic bronchitis or chronic sinusitis. Electron microscopy of the siblings revealed a new abnormality in the ciliary axoneme--namely, lack of the radial spokes. Their cilia showed an eccentric central pair of tubules but otherwise had a normal central sheath, outer-doublet microtubules, nexin links and dynein arms. The cilia were immotile. Mucociliary clearance was completely lacking in the three siblings and in the patient with Kartagener's syndrome, but was normal in their parents and unaffected siblings. Sperm from the male sibling showed identical structural abnormalities and were immotile. We consider the radial spoke defect to be the congenital anomaly responsible for dysfunction of the mucociliary clearance mechanism in these three patients and of the immotile sperm in one of the them. This defect is apparently another cause of the \"immotilecilia syndrome.\""} {"id": "PMID:152871", "title": "[The superior facet syndrome--report of three cases and a review of the literature (author's transl)].", "content": "Within the past 6 months we paid special attention to the superior facet syndrome on examining the patients with lumbar pain at the outpatient clinic. Out of 264 patients who complained of lumbago or sciatica, this syndrome was suspected in three patients and verified in all of them by operation. Neurologically it was difficult to differentiate this syndrome from disc protrusion or other related conditions. On the other hand, plain roentgenographic examinations were valuable: horizontal portion of the superior facet was larger and thicker than normal so that the a-p view of the lumbar spine showed a large bulbous processes joining in the frontal plane, and a narrowing of the interlaminal spaces was seen in some case. A differential diagnosis between this syndrome and the major type of lumbar canal stenosis can be made by means of dynamic myelography. Although the myelography with watersoluble contrast medium reveals nerve roots better than Myodil myelography, identification of the nerve roots at the lateral recesses is not necessarily easy, and the final diagnosis has to be made at operation.", "contents": "[The superior facet syndrome--report of three cases and a review of the literature (author's transl)]. Within the past 6 months we paid special attention to the superior facet syndrome on examining the patients with lumbar pain at the outpatient clinic. Out of 264 patients who complained of lumbago or sciatica, this syndrome was suspected in three patients and verified in all of them by operation. Neurologically it was difficult to differentiate this syndrome from disc protrusion or other related conditions. On the other hand, plain roentgenographic examinations were valuable: horizontal portion of the superior facet was larger and thicker than normal so that the a-p view of the lumbar spine showed a large bulbous processes joining in the frontal plane, and a narrowing of the interlaminal spaces was seen in some case. A differential diagnosis between this syndrome and the major type of lumbar canal stenosis can be made by means of dynamic myelography. Although the myelography with watersoluble contrast medium reveals nerve roots better than Myodil myelography, identification of the nerve roots at the lateral recesses is not necessarily easy, and the final diagnosis has to be made at operation."} {"id": "PMID:152877", "title": "Chromosome studies of embryos from induced abortions in pregnant women age 35 and over.", "content": "Chromosome studies of embryos were done in abortions induced at the early stage of pregnancy in women 35 years of age and older who had no signs of threatened or spontaneous abortions and were considered to have oocytes of an advanced age. Karyotypes were successfully determined in 256 cases and the results were as follows: a) 2 of 123 cases in 35- to 39-year-old women showed an incidence of chromosomal anomalies as high as 1.6%; 7 of 117 cases in 40- to 44-year-old mothers an incidence of 6.0%; and 4 of 16 mothers in the 45- to 49-year-old age group an incidence of 25.0%; b) all chromosomal anomalies were trisomies, mainly trisomy 21 and 18. These results suggest that the incidence of chromosomal anomalies increases in older pregnant women, especially in premenopausal pregnancies, and that non-disjunction may occur during meiosis.", "contents": "Chromosome studies of embryos from induced abortions in pregnant women age 35 and over. Chromosome studies of embryos were done in abortions induced at the early stage of pregnancy in women 35 years of age and older who had no signs of threatened or spontaneous abortions and were considered to have oocytes of an advanced age. Karyotypes were successfully determined in 256 cases and the results were as follows: a) 2 of 123 cases in 35- to 39-year-old women showed an incidence of chromosomal anomalies as high as 1.6%; 7 of 117 cases in 40- to 44-year-old mothers an incidence of 6.0%; and 4 of 16 mothers in the 45- to 49-year-old age group an incidence of 25.0%; b) all chromosomal anomalies were trisomies, mainly trisomy 21 and 18. These results suggest that the incidence of chromosomal anomalies increases in older pregnant women, especially in premenopausal pregnancies, and that non-disjunction may occur during meiosis."} {"id": "PMID:152878", "title": "Unruptured interstitial pregnancy. Diagnosis and treatment.", "content": "Symptoms and signs of interstitial pregnancy cannot be differentiated from symptoms and signs of other ectopic pregnancies. Unruptured interstitial gestations are usually diagnosed incidental to the work-up of a suspected ectopic gestation. Unlike some teaching, a characteristic pelvic mass was palpable in 3 of 4 cases. Incomplete induced abortion helped in diagnosing 2 cases. Ultrasound and laparoscopy will aid in establishing the correct diagnosis.", "contents": "Unruptured interstitial pregnancy. Diagnosis and treatment. Symptoms and signs of interstitial pregnancy cannot be differentiated from symptoms and signs of other ectopic pregnancies. Unruptured interstitial gestations are usually diagnosed incidental to the work-up of a suspected ectopic gestation. Unlike some teaching, a characteristic pelvic mass was palpable in 3 of 4 cases. Incomplete induced abortion helped in diagnosing 2 cases. Ultrasound and laparoscopy will aid in establishing the correct diagnosis."} {"id": "PMID:152895", "title": "Echocardiography in infants and children.", "content": "Echocardiography is a well established, non-invasive diagnostic technique that has assumed a prominent place in the armamentarium of the pediatric cardiologist. The principles and techniques of echocardiography are explained. In addition, the measurements and interpretation are described, as well as the deductive approach that leads to a specific diagnosis. The purpose of this discussion is to provide the pediatrician with an understanding of the appropriate application, value, and limitation of the echocardiogram.", "contents": "Echocardiography in infants and children. Echocardiography is a well established, non-invasive diagnostic technique that has assumed a prominent place in the armamentarium of the pediatric cardiologist. The principles and techniques of echocardiography are explained. In addition, the measurements and interpretation are described, as well as the deductive approach that leads to a specific diagnosis. The purpose of this discussion is to provide the pediatrician with an understanding of the appropriate application, value, and limitation of the echocardiogram."} {"id": "PMID:152896", "title": "Genetic emergencies in pediatrics.", "content": "Genetic emergencies like other medical emergencies require immediate intervention to alter the outcome of the condition in the patient and its effect upon the family. The representative conditions of myelomeningocele, Down's syndrome, cleft lip and palate and adrenogenital syndrome serve to illustrate the need for rapid and comprehensive intervention. Recognition that an emergency exists when a child with a birth defect is born and responsive thoughtful action including family counseling can significantly alter the life of the patient and his family.", "contents": "Genetic emergencies in pediatrics. Genetic emergencies like other medical emergencies require immediate intervention to alter the outcome of the condition in the patient and its effect upon the family. The representative conditions of myelomeningocele, Down's syndrome, cleft lip and palate and adrenogenital syndrome serve to illustrate the need for rapid and comprehensive intervention. Recognition that an emergency exists when a child with a birth defect is born and responsive thoughtful action including family counseling can significantly alter the life of the patient and his family."} {"id": "PMID:152900", "title": "Bulbospinal tryptaminergic neurones. A search for the role of bulbospinal tryptaminergic neurones in the control of sympathetic activity.", "content": "1. The possible role of bulbospinal tryptaminergic neurones in the control of sympathetic activity has been investigated in anaesthetised cats. 2. Depletion of spinal cord stores of 5-hydroxytryptamine was achieved by systemic administration of p-chlorophenylalanine or by intraspinal microinjections of 5,6-dihydroxytryptamine. 3. Blood pressure was little changed by these treatments, neither was the pattern of ongoing activity in sympathetic nerves (arterial pulse rhythmicity and respiratory modulation), the influence of pulmonary afferent nerves on this activity (determined by an airway occlusion technique), the sympatho-inhibitory influence of the carotid sinus baroreceptors, nor the sympatho-inhibitory or -excitatory influences of somatic afferent nerves. 4. Since both p-chlorophenylalanine and 5,6-dihydroxytryptamine treatment caused extensive disruption of the bulbospinal tryptaminergic neurones, it was concluded that these play no significant role in the mediation of the responses tested in anaesthetised cats in the present study.", "contents": "Bulbospinal tryptaminergic neurones. A search for the role of bulbospinal tryptaminergic neurones in the control of sympathetic activity. 1. The possible role of bulbospinal tryptaminergic neurones in the control of sympathetic activity has been investigated in anaesthetised cats. 2. Depletion of spinal cord stores of 5-hydroxytryptamine was achieved by systemic administration of p-chlorophenylalanine or by intraspinal microinjections of 5,6-dihydroxytryptamine. 3. Blood pressure was little changed by these treatments, neither was the pattern of ongoing activity in sympathetic nerves (arterial pulse rhythmicity and respiratory modulation), the influence of pulmonary afferent nerves on this activity (determined by an airway occlusion technique), the sympatho-inhibitory influence of the carotid sinus baroreceptors, nor the sympatho-inhibitory or -excitatory influences of somatic afferent nerves. 4. Since both p-chlorophenylalanine and 5,6-dihydroxytryptamine treatment caused extensive disruption of the bulbospinal tryptaminergic neurones, it was concluded that these play no significant role in the mediation of the responses tested in anaesthetised cats in the present study."} {"id": "PMID:152902", "title": "Problems in the rehabilitation of the physically disabled in rural areas of India.", "content": "Some 550 disabled patients were examined by a rehabilitation team by organizing a rural camp at Meerut. This rehabilitation team consisted of orthopaedic surgeons, doctors, a prosthetist, an orthotist, a medical social worker and other skilled workers. Out of the 550 disabled patients, 271 were amputees, and 184 cases had poliomyelitis. Males predominated by 4:1. Disability was most common up to the age of 30 years. Of the 271 amputees, 146 were of upper limb while 125 were of lower limb. Only 86 lower limb amputees were suitable for fitting a prosthesis, while 39 others needed surgery of physiotherapy. Only 87 of the 184 polio cases were found suitable for appliances, the remainder needing surgery or physiotherapy. Ways of reducing the numbers of disabled were examined and improved rehabilitation procedures suggested.", "contents": "Problems in the rehabilitation of the physically disabled in rural areas of India. Some 550 disabled patients were examined by a rehabilitation team by organizing a rural camp at Meerut. This rehabilitation team consisted of orthopaedic surgeons, doctors, a prosthetist, an orthotist, a medical social worker and other skilled workers. Out of the 550 disabled patients, 271 were amputees, and 184 cases had poliomyelitis. Males predominated by 4:1. Disability was most common up to the age of 30 years. Of the 271 amputees, 146 were of upper limb while 125 were of lower limb. Only 86 lower limb amputees were suitable for fitting a prosthesis, while 39 others needed surgery of physiotherapy. Only 87 of the 184 polio cases were found suitable for appliances, the remainder needing surgery or physiotherapy. Ways of reducing the numbers of disabled were examined and improved rehabilitation procedures suggested."} {"id": "PMID:152903", "title": "Moulded supportive seating for the disabled.", "content": "In severe cases of physical disability intimate supportive seating may be required to provide maximum comfort, a good position for functional activities, improved respiration, relief of localized pressure, control of spasm, protection, or improved management. A service for providing such seating has been developed at Chailey Heritage. The seat is vacuum-formed from thermoplastic materials, having a soft non-absorbent foam for the linear and a hard semi-rigid outer shell. A mould is obtained by casting the patient using the vacuum consolidation technique and by recording the resulting impression using plaster-of-Paris. Nearly 200 seats have been made using the technique with a high rate of success.", "contents": "Moulded supportive seating for the disabled. In severe cases of physical disability intimate supportive seating may be required to provide maximum comfort, a good position for functional activities, improved respiration, relief of localized pressure, control of spasm, protection, or improved management. A service for providing such seating has been developed at Chailey Heritage. The seat is vacuum-formed from thermoplastic materials, having a soft non-absorbent foam for the linear and a hard semi-rigid outer shell. A mould is obtained by casting the patient using the vacuum consolidation technique and by recording the resulting impression using plaster-of-Paris. Nearly 200 seats have been made using the technique with a high rate of success."} {"id": "PMID:152904", "title": "The Orlau swivel walker.", "content": "A new design of swivel walker for the severely disabled is described which has advantages over previous types. Increased rigidity improves the confidence of apprehensive patients, greater strength gives better reliability for those with good ambulation function and a novel construction gives more opportunity for independent transfer into and out of the orthosis, besides easing the burden of those caring for users of swivel walkers.", "contents": "The Orlau swivel walker. A new design of swivel walker for the severely disabled is described which has advantages over previous types. Increased rigidity improves the confidence of apprehensive patients, greater strength gives better reliability for those with good ambulation function and a novel construction gives more opportunity for independent transfer into and out of the orthosis, besides easing the burden of those caring for users of swivel walkers."} {"id": "PMID:152906", "title": "The use of lumbosacral corsets prescribed for low back pain.", "content": "Two hundred and one randomly selected patients (109 women and 92 men) fitted with their first lumbosacral corset because of low back pain were interviewed 3.5--4.5 years later. Two-thirds of the patients were 41--70 years when fitted with the corset. Barely three-quarters of them wore the corset regularly immediately after prescription. One-fifth became symptom-free within the period covered by the study. Of those who still had symptoms at the time of the interview, two-thirds (about half of the original material) were still wearing a corset. Of these two-thirds, about half wore the corset at least once a week. The women doing heavy work and female pensioners tended to use their corsets more frequently. The frequency with which the corsets were used was not influenced by the clinical diagnosis or the type of corset used. As many as 89 per cent of the patients reported that they used the corset because it supported their back or because it not only gave such support, but also relief from the pain. Thirty-seven of 96 non-users reported that the corset did not fit well but only 7 that they did not benefit from the use of the corset. A better follow-up of users would surely increase the frequency with which such corsets are used to the advantage of the patients.", "contents": "The use of lumbosacral corsets prescribed for low back pain. Two hundred and one randomly selected patients (109 women and 92 men) fitted with their first lumbosacral corset because of low back pain were interviewed 3.5--4.5 years later. Two-thirds of the patients were 41--70 years when fitted with the corset. Barely three-quarters of them wore the corset regularly immediately after prescription. One-fifth became symptom-free within the period covered by the study. Of those who still had symptoms at the time of the interview, two-thirds (about half of the original material) were still wearing a corset. Of these two-thirds, about half wore the corset at least once a week. The women doing heavy work and female pensioners tended to use their corsets more frequently. The frequency with which the corsets were used was not influenced by the clinical diagnosis or the type of corset used. As many as 89 per cent of the patients reported that they used the corset because it supported their back or because it not only gave such support, but also relief from the pain. Thirty-seven of 96 non-users reported that the corset did not fit well but only 7 that they did not benefit from the use of the corset. A better follow-up of users would surely increase the frequency with which such corsets are used to the advantage of the patients."} {"id": "PMID:152909", "title": "The value of flexor hinge hand splints.", "content": "Functional hand splints have been in use in a number of spinal injury units in the USA since the early 1950s. The splints are designed to provide a pinch-grip either by harnessing wrist dorsiflexion or by external power. Such devices are little used in the United Kingdom. This paper describes the results of late provision of 62 such splints in a Disabled Living Unit. A proportion of tetraplegic patients found such splints of considerable functional value. It is estimated that some 30--60 patients each year would benefit from them if appropriate facilities for early fitting were available.", "contents": "The value of flexor hinge hand splints. Functional hand splints have been in use in a number of spinal injury units in the USA since the early 1950s. The splints are designed to provide a pinch-grip either by harnessing wrist dorsiflexion or by external power. Such devices are little used in the United Kingdom. This paper describes the results of late provision of 62 such splints in a Disabled Living Unit. A proportion of tetraplegic patients found such splints of considerable functional value. It is estimated that some 30--60 patients each year would benefit from them if appropriate facilities for early fitting were available."} {"id": "PMID:152914", "title": "[Glucoamylase immobilized on AE-cellulose].", "content": "Glucoamylase from Endomycopsis species 20-9 was immobilized on AE-cellulose by covalent binding with the use of glutaraldehyde. The activity of immobilized preparations was measured as a function of pH, buffer concentration, temperature and immobilization time. The most active preparations of immobilized glucoamylase were obtained in 0.2 M Na-phosphate buffer, pH 5.0--7.0 at 4--20 degrees C for 4--24 hrs. In the presence of substrate--starch the activity of immobilized glucoamylase increased almost two-fold whereas glucose had no effect of this kind.", "contents": "[Glucoamylase immobilized on AE-cellulose]. Glucoamylase from Endomycopsis species 20-9 was immobilized on AE-cellulose by covalent binding with the use of glutaraldehyde. The activity of immobilized preparations was measured as a function of pH, buffer concentration, temperature and immobilization time. The most active preparations of immobilized glucoamylase were obtained in 0.2 M Na-phosphate buffer, pH 5.0--7.0 at 4--20 degrees C for 4--24 hrs. In the presence of substrate--starch the activity of immobilized glucoamylase increased almost two-fold whereas glucose had no effect of this kind."} {"id": "PMID:152916", "title": "[Preventive effect of inhibitors of catecholamine synthesis, serotonin and adrenoblockaders on anovulatory syndrome development in neonatally androgenized rats. 2].", "content": "Administration to female rats of 250 micrograms of testosterone propionate (TSP) on the 3rd day of postnatal life led to reduction of estradiol, progesterone, and, to a lesser degree, of lutropin in the blood plasma of these animals at the age of 3 months. There was an increase of the lutropin content in the adenohypophysis and of luliberin in the hypothalamus. Combined with TSP administration of alpha-methyl-p-tyrosine, p-chlorphenylalanine or droperidol promoted preservation of cyclic changes in the hypothalamic gonadotropin activity and partially prevented disturbances of estradiol and progesteron secretion caused by neonatal androgenization. The mechanisms of participation of biogenic monoamines in sex differentiation of the hypothalamus are discussed.", "contents": "[Preventive effect of inhibitors of catecholamine synthesis, serotonin and adrenoblockaders on anovulatory syndrome development in neonatally androgenized rats. 2]. Administration to female rats of 250 micrograms of testosterone propionate (TSP) on the 3rd day of postnatal life led to reduction of estradiol, progesterone, and, to a lesser degree, of lutropin in the blood plasma of these animals at the age of 3 months. There was an increase of the lutropin content in the adenohypophysis and of luliberin in the hypothalamus. Combined with TSP administration of alpha-methyl-p-tyrosine, p-chlorphenylalanine or droperidol promoted preservation of cyclic changes in the hypothalamic gonadotropin activity and partially prevented disturbances of estradiol and progesteron secretion caused by neonatal androgenization. The mechanisms of participation of biogenic monoamines in sex differentiation of the hypothalamus are discussed."} {"id": "PMID:152921", "title": "Reductant-dependent electron distribution among redox sites of laccase.", "content": "Rhus laccase (monophenol monooxygenase, monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) an O2/H2O oxidoreductase containing four copper ions bound to three redox sites (type 1, type 2, and type 3 Cu pair), was titrated anaerobically with several reductants having various chemical and thermodynamic properties. The distribution of electron equivalents among the redox sites was found to be reductant dependent. When the data for titration by various reductants of the type 3 site were plotted against those of the type 1 site according to the Nernst formalism, the slope n varied from 2.0 to 1.0. The redox potential of the reductant's first oxidation step is qualitatively correlated with the value of n and is suggested as the factor that modulates the electron distribution. Such a behavior implies a nonequilibrium situation. A very good simulation of the data was provided by an analysis assuming a formally variable cooperativity between the two type 3 copper ions. This apparent variability is suggested to result from a process whereby sufficiently strong reductants induce a transition of the type 3 site from a cooperative two-electron acceptor to a pair of independent one-electron acceptors. This uncoupled state of the type 3 site is considered metastable. Other possible models were also investigated. Summarizing the available data, we conclude that the two-electron accepting behavior of the 330-nm chromophore is the exception rather than the rule.", "contents": "Reductant-dependent electron distribution among redox sites of laccase. Rhus laccase (monophenol monooxygenase, monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) an O2/H2O oxidoreductase containing four copper ions bound to three redox sites (type 1, type 2, and type 3 Cu pair), was titrated anaerobically with several reductants having various chemical and thermodynamic properties. The distribution of electron equivalents among the redox sites was found to be reductant dependent. When the data for titration by various reductants of the type 3 site were plotted against those of the type 1 site according to the Nernst formalism, the slope n varied from 2.0 to 1.0. The redox potential of the reductant's first oxidation step is qualitatively correlated with the value of n and is suggested as the factor that modulates the electron distribution. Such a behavior implies a nonequilibrium situation. A very good simulation of the data was provided by an analysis assuming a formally variable cooperativity between the two type 3 copper ions. This apparent variability is suggested to result from a process whereby sufficiently strong reductants induce a transition of the type 3 site from a cooperative two-electron acceptor to a pair of independent one-electron acceptors. This uncoupled state of the type 3 site is considered metastable. Other possible models were also investigated. Summarizing the available data, we conclude that the two-electron accepting behavior of the 330-nm chromophore is the exception rather than the rule."} {"id": "PMID:152922", "title": "Nerve growth factor: a protease that can activate plasminogen.", "content": "The single, highly stable form of mouse submandibular gland nerve growth factor (NGF), prepared as described by Young et al. [(1978) Biochemistry 17, 1490--1498] is a protease of restricted specificity that can convert plasminogen to plasmin. In the absence of plasminogen, NGF is not fibrinolytic, nor does it hydrolyze casein at a measurable rate. Treatment of NGF with diisopropyl fluorophosphate inhibits its ability to activate plasminogen as well as its capacity to hydrolyze certain synthetic arginine esters. These results indicate that NGF is a member of the class of serine proteases. Since NGF is known to be secreted at high concentrations in mouse saliva, it may serve to activate plasminogen (with subsequent fibrinolysis) somewhere in the alimentary tract. Plasminogen activation is the only known action of NGF upon a biologically important non-neural substrate.", "contents": "Nerve growth factor: a protease that can activate plasminogen. The single, highly stable form of mouse submandibular gland nerve growth factor (NGF), prepared as described by Young et al. [(1978) Biochemistry 17, 1490--1498] is a protease of restricted specificity that can convert plasminogen to plasmin. In the absence of plasminogen, NGF is not fibrinolytic, nor does it hydrolyze casein at a measurable rate. Treatment of NGF with diisopropyl fluorophosphate inhibits its ability to activate plasminogen as well as its capacity to hydrolyze certain synthetic arginine esters. These results indicate that NGF is a member of the class of serine proteases. Since NGF is known to be secreted at high concentrations in mouse saliva, it may serve to activate plasminogen (with subsequent fibrinolysis) somewhere in the alimentary tract. Plasminogen activation is the only known action of NGF upon a biologically important non-neural substrate."} {"id": "PMID:152925", "title": "Non-specific neural stimuli and metabolic rhythms in rats.", "content": "Ten rats housed in individual metabolism cages in a room next to a teaching laboratory showed rhythmic fluctuations in urination and defaecation. Sectral analysis of the data indicates a weekly rhythm which is attributed to the lack of neural stimuli at the weekend. Regression analysis using a weekly cycle illustrates this effect.", "contents": "Non-specific neural stimuli and metabolic rhythms in rats. Ten rats housed in individual metabolism cages in a room next to a teaching laboratory showed rhythmic fluctuations in urination and defaecation. Sectral analysis of the data indicates a weekly rhythm which is attributed to the lack of neural stimuli at the weekend. Regression analysis using a weekly cycle illustrates this effect."} {"id": "PMID:152927", "title": "Influence of D-penicillamine on the formation of elastin and its cross-links.", "content": "The amount of insoluble elastin and its content of desmosine cross-links were investigated in aortas of chick embryos, to which D-penicillamine was administered on the 6th or 14th--16th day of incubation. D-Penicillamine was shown to alter the formation and maturation of elastin. Using lower doses (less than 50 mg) the weight of pooled aortic elastin is higher as compared with controls (related to 1 mg of elastin or to total weight of elastin). Increased isodesmosine:desmosine ratio in these samples indicates that this elastin is very young. On the other hand, a high dose of D-penicillamine (100 mg) decreased the content of elastin and also of its desmosine cross-links. The authors explain their findings by counteraction of two factors due to administration of penicillamine: the increased solubility of \"insoluble elastin\", and the decreased cross-link formation.", "contents": "Influence of D-penicillamine on the formation of elastin and its cross-links. The amount of insoluble elastin and its content of desmosine cross-links were investigated in aortas of chick embryos, to which D-penicillamine was administered on the 6th or 14th--16th day of incubation. D-Penicillamine was shown to alter the formation and maturation of elastin. Using lower doses (less than 50 mg) the weight of pooled aortic elastin is higher as compared with controls (related to 1 mg of elastin or to total weight of elastin). Increased isodesmosine:desmosine ratio in these samples indicates that this elastin is very young. On the other hand, a high dose of D-penicillamine (100 mg) decreased the content of elastin and also of its desmosine cross-links. The authors explain their findings by counteraction of two factors due to administration of penicillamine: the increased solubility of \"insoluble elastin\", and the decreased cross-link formation."} {"id": "PMID:152936", "title": "Cardiopulmonary effects of intravenous fluid overload: radiologic manifestations.", "content": "Large volumes of normal saline were infused intravenously in 6 dogs until obvious pulmonary edema was observed radiographically. Following volume overload, statistically significant increases occurred in the size of the heart, left atrium, pulmonary arteries and veins, and systemic veins, without the development of congestive heart failure (CHF). The left ventricular end-diastolic pressure remained normal, and cardiac output and stroke volume increased. The results suggest that, in the absence of left ventricular failure, acute volume overload may simulate the radiographic changes produced by CHF. Pulmonary edema may have occurred at least partly from a marked decrease in serum colloid osmotic pressure.", "contents": "Cardiopulmonary effects of intravenous fluid overload: radiologic manifestations. Large volumes of normal saline were infused intravenously in 6 dogs until obvious pulmonary edema was observed radiographically. Following volume overload, statistically significant increases occurred in the size of the heart, left atrium, pulmonary arteries and veins, and systemic veins, without the development of congestive heart failure (CHF). The left ventricular end-diastolic pressure remained normal, and cardiac output and stroke volume increased. The results suggest that, in the absence of left ventricular failure, acute volume overload may simulate the radiographic changes produced by CHF. Pulmonary edema may have occurred at least partly from a marked decrease in serum colloid osmotic pressure."} {"id": "PMID:152937", "title": "The effect of dehydration on the side effects of metrizamide myelography.", "content": "The effect of dehydration on the incidence of side effects from metrizamide myelography was studied. One hundred consecutive patients scheduled for myelography fasted overnight and were then randomly divided into two groups. Group I received 2 liters of fluid intravenously just prior to myelography; Group II did not. Both groups were studied in the standard manner, using 170 mg l/ml of metrizamide. Side effects were recorded 24 and 48 hours after the procedure. Headaches, vomiting, and some other side effects were less common and less severe in the hydrated group. Clear liquids given orally or intravenous fluids are recommended prior to myelography to minimize side effects.", "contents": "The effect of dehydration on the side effects of metrizamide myelography. The effect of dehydration on the incidence of side effects from metrizamide myelography was studied. One hundred consecutive patients scheduled for myelography fasted overnight and were then randomly divided into two groups. Group I received 2 liters of fluid intravenously just prior to myelography; Group II did not. Both groups were studied in the standard manner, using 170 mg l/ml of metrizamide. Side effects were recorded 24 and 48 hours after the procedure. Headaches, vomiting, and some other side effects were less common and less severe in the hydrated group. Clear liquids given orally or intravenous fluids are recommended prior to myelography to minimize side effects."} {"id": "PMID:152938", "title": "Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats.", "content": "Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 mm Hg). After two weeks all were injected intravenously with 50 muCi of 201Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension.", "contents": "Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats. Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 mm Hg). After two weeks all were injected intravenously with 50 muCi of 201Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension."} {"id": "PMID:152944", "title": "[The use of a hinge distraction apparatus after arthrolysis and arthroplasty (author's transl)].", "content": "The authors describe a hinge distraction apparatus which allows physiological movement of joints following surgical procedures such as arthrolysis or arthroplasty. The apparatus maintains some space between the bone ends and provides lateral stability. It is based on the principles of external fixation. The apparatus has been used for ankles, knees, and elbows. Thirty-eight patients were operated on. The technique is fully described. The results on experimental work in the dog are given. At the ankle, the authors have shown that the use of the apparatus allows the formation of fibrous tissue between the bone ends. The indications and results obtained at the level of the knee and elbow are discussed.", "contents": "[The use of a hinge distraction apparatus after arthrolysis and arthroplasty (author's transl)]. The authors describe a hinge distraction apparatus which allows physiological movement of joints following surgical procedures such as arthrolysis or arthroplasty. The apparatus maintains some space between the bone ends and provides lateral stability. It is based on the principles of external fixation. The apparatus has been used for ankles, knees, and elbows. Thirty-eight patients were operated on. The technique is fully described. The results on experimental work in the dog are given. At the ankle, the authors have shown that the use of the apparatus allows the formation of fibrous tissue between the bone ends. The indications and results obtained at the level of the knee and elbow are discussed."} {"id": "PMID:152945", "title": "[Hemimelica epiphysialis dysplasia (author's transl)].", "content": "Hemimelica Epiphysialis Dysplasia is a rare osteochondrodystrophy producing cartilaginous epiphysial hypertrophy with hemimelic topography involving preferentialy the lower limb. Lesions are generally medialy situated (medial condyle of the femur, medial malleolus talus, tarsal scaphoid and first metatarsal bone). 8 cases of patients are discussed with a follow up of 4 years. The evolution is to a massive ossification of the hypertrophic cartilaginous areas. The issue is a fast arthrosic degeneration of the involved joints (mainly the ankle, more rarely the knee). The surgical procedures are often unsuccessful.", "contents": "[Hemimelica epiphysialis dysplasia (author's transl)]. Hemimelica Epiphysialis Dysplasia is a rare osteochondrodystrophy producing cartilaginous epiphysial hypertrophy with hemimelic topography involving preferentialy the lower limb. Lesions are generally medialy situated (medial condyle of the femur, medial malleolus talus, tarsal scaphoid and first metatarsal bone). 8 cases of patients are discussed with a follow up of 4 years. The evolution is to a massive ossification of the hypertrophic cartilaginous areas. The issue is a fast arthrosic degeneration of the involved joints (mainly the ankle, more rarely the knee). The surgical procedures are often unsuccessful."} {"id": "PMID:152946", "title": "[Ectopic bone formation in neurological lesions (author's transl)].", "content": "The authors have operated on seventy instances of para-articular ectopic bone formation in fifty patients. Seventeen were paraplegic or tetraplegic, thirty were the result of trauma, two resulted from meningitis and one was a sequel of burns. The ectopic bone was located at the hip (thirty-three cases), the elbow (twenty-three cases), the knee (twelve cases) and the shoulder (two cases). The clinical, radiological and pathological features are reviewed. Several hypotheses on the mechanism of ectopic bone formation are put forward. The surgical procedures have included arthrolysis, arthrodesis, wide resection of the epiphysis, and total prostheses. There were ten recurrences. The authors conclude that the most extensive lesions occur in paraplegia and when the bone formation is situated at the hip.", "contents": "[Ectopic bone formation in neurological lesions (author's transl)]. The authors have operated on seventy instances of para-articular ectopic bone formation in fifty patients. Seventeen were paraplegic or tetraplegic, thirty were the result of trauma, two resulted from meningitis and one was a sequel of burns. The ectopic bone was located at the hip (thirty-three cases), the elbow (twenty-three cases), the knee (twelve cases) and the shoulder (two cases). The clinical, radiological and pathological features are reviewed. Several hypotheses on the mechanism of ectopic bone formation are put forward. The surgical procedures have included arthrolysis, arthrodesis, wide resection of the epiphysis, and total prostheses. There were ten recurrences. The authors conclude that the most extensive lesions occur in paraplegia and when the bone formation is situated at the hip."} {"id": "PMID:152947", "title": "[The treatment of diaphyso-epiphyseal tumours by local resection with the preservation of joint movement. A report of four cases (author's transl)].", "content": "Four cases of epiphyseal tumours were treated by the authors by local resection. In two cases, there was a giant-cell tumour of the lower end of the femur, in one case a giant-cell tumour of the lower end of the radius and in one case a juxta-cortical sarcoma of the lower end of the radius. In the two cases involving the knees, resection preserved the articular surface and the subchondral bone. Reconstruction was achieved by a cortical autograft. In all cases, painless joint movement was preserved with satisfactory muscle power.", "contents": "[The treatment of diaphyso-epiphyseal tumours by local resection with the preservation of joint movement. A report of four cases (author's transl)]. Four cases of epiphyseal tumours were treated by the authors by local resection. In two cases, there was a giant-cell tumour of the lower end of the femur, in one case a giant-cell tumour of the lower end of the radius and in one case a juxta-cortical sarcoma of the lower end of the radius. In the two cases involving the knees, resection preserved the articular surface and the subchondral bone. Reconstruction was achieved by a cortical autograft. In all cases, painless joint movement was preserved with satisfactory muscle power."} {"id": "PMID:152948", "title": "[Upper brachial plexus palsy. Seven cases treated by muscle transplantation (author's transl)].", "content": "Seven cases of upper brachial plexus palsy, have been treated by associated transplantation of pectoralis major for flexion, and of teres major and latissimus dorsi for external rotation. Operation was performed eighteen months at least after injury, during which period rehabilitation was necessary to prevent atrophy of the pectoralis major and contracture in internal rotation. The strength of flexion was improved by alterations of the original Clark's operation. The whole muscle was transplanted: its humeral tendon was fixed to the coracoid process; its thoracic extremity lengthened by an aponevrotic flap from rectus anterior was pulled through a posterior anti-brachial incision, holding the arm in anteposition and the forearm in supination. A strong tension was obtained in this way. Transplantation of teres major and latissimus dorsi tendons behind the humerus was done in the same stage. Results are in favor of these improvements: all seven patients, including two hard-workers, obtained a strong and large flexion. The useful part of external rotation was restored. All went back to their former occupations.", "contents": "[Upper brachial plexus palsy. Seven cases treated by muscle transplantation (author's transl)]. Seven cases of upper brachial plexus palsy, have been treated by associated transplantation of pectoralis major for flexion, and of teres major and latissimus dorsi for external rotation. Operation was performed eighteen months at least after injury, during which period rehabilitation was necessary to prevent atrophy of the pectoralis major and contracture in internal rotation. The strength of flexion was improved by alterations of the original Clark's operation. The whole muscle was transplanted: its humeral tendon was fixed to the coracoid process; its thoracic extremity lengthened by an aponevrotic flap from rectus anterior was pulled through a posterior anti-brachial incision, holding the arm in anteposition and the forearm in supination. A strong tension was obtained in this way. Transplantation of teres major and latissimus dorsi tendons behind the humerus was done in the same stage. Results are in favor of these improvements: all seven patients, including two hard-workers, obtained a strong and large flexion. The useful part of external rotation was restored. All went back to their former occupations."} {"id": "PMID:152949", "title": "[Reconstructive surgery of the thumb after traumatic amputation (author's transl)].", "content": "The authors analysed the results of two series of patients treated either by lengthening (16 cases) or digital pollicization (45 cases). The conclusions about the indications for the two techniques are as follows: When the amputation is proximal and the sole lesion, pollicization of the ring finger is preferred. In distal amputations in children, pollicization is still indicated, but in adults, lengthening, with a pedicle island-flap to give sensation is preferable. In amputations of the thumb associated with lesions of other digits, pollicization is not feasible; in these cases, the authors recommend a toe transplant using micro-surgical technique.", "contents": "[Reconstructive surgery of the thumb after traumatic amputation (author's transl)]. The authors analysed the results of two series of patients treated either by lengthening (16 cases) or digital pollicization (45 cases). The conclusions about the indications for the two techniques are as follows: When the amputation is proximal and the sole lesion, pollicization of the ring finger is preferred. In distal amputations in children, pollicization is still indicated, but in adults, lengthening, with a pedicle island-flap to give sensation is preferable. In amputations of the thumb associated with lesions of other digits, pollicization is not feasible; in these cases, the authors recommend a toe transplant using micro-surgical technique."} {"id": "PMID:152953", "title": "[The medius gluteus with 1-legged stance. Geometric variations on the theme of femoral and pelvic osteotomies].", "content": "The work of Pauwels has supplied evidence of the pressure applied to the hip by the contraction of the gluteus medius as its acts to maintain the pelvis in equilibrium when weight is born on one limb. The force exerted by the gluteus medius is greater the larger the distance separating the gluteus medius from the centre of the femoral head compared with the distance separating the femoral head from the centre of gravity. It is this force that mechanical procedures such as osteotomy of the femur or pelvis attempt to diminish. A study was made in depth of the variations in the activity of the gluteus medius with regard to various parameters including not only the gluteus medius distance (parameter of Pauwels) but also of the direction of the muscle and the angle formed by the cephalo-trochanteric line below and the iliac wing above the ilio-trochanteric angle. Using routine radiographs to act as a geometric model, a method was devised based on a combination of geometric construction, an experimental study and trigonometric calculation. Curves have been established determining the value of the force exerted by the gluteus medius in relation to the ilio-trochanteric angle. The smallest force exerted by the gluteus medius corresponds to the lower pole of the curve and arises when the cephalo-trochanteric line is perpendicular to the direction of the muscle; the force is greatest in the highest and lowest positions of the tip of the great trochanter, that is to say on either side of the lower pole of the curve. Since the position of the greater trochanter is, in practice, always lower, it can be said that, as a general rule, angulation into varus diminishes the tension of the gluteus medius whilst angulation into valgus increases it. However, contrary to current opinion, the effect produced on the force applied by the gluteus medius is not proportional to the ammount of varisization. The effectiveness of a varisization is greater the more the hip is in valgus and there is a critical zone with increasing varus where the effect becomes minimal. Displacement of the femoral shaft (McMurray's operation) has little effect. In Chiari's operation, diminution of the ilio-trochanteric angle and shortening of the medial lever with lengthening of the lateral lever by medial transposition of the point of application of the femoral head diminishes the force required of the gluteus medius very effectively. In particular, the effect of Chiari's operation is greater when the hip is displaced or there is coxa valga. The method described allows a precise calculation to be made on a tracing of the patient's radiograph of the effect to the proposed operation on the force required by the gluteus medius. The different parameters could be applied to a computer and thus allows statistical definition of anthropometric date concerning the force of contraction of the gluteus medius.", "contents": "[The medius gluteus with 1-legged stance. Geometric variations on the theme of femoral and pelvic osteotomies]. The work of Pauwels has supplied evidence of the pressure applied to the hip by the contraction of the gluteus medius as its acts to maintain the pelvis in equilibrium when weight is born on one limb. The force exerted by the gluteus medius is greater the larger the distance separating the gluteus medius from the centre of the femoral head compared with the distance separating the femoral head from the centre of gravity. It is this force that mechanical procedures such as osteotomy of the femur or pelvis attempt to diminish. A study was made in depth of the variations in the activity of the gluteus medius with regard to various parameters including not only the gluteus medius distance (parameter of Pauwels) but also of the direction of the muscle and the angle formed by the cephalo-trochanteric line below and the iliac wing above the ilio-trochanteric angle. Using routine radiographs to act as a geometric model, a method was devised based on a combination of geometric construction, an experimental study and trigonometric calculation. Curves have been established determining the value of the force exerted by the gluteus medius in relation to the ilio-trochanteric angle. The smallest force exerted by the gluteus medius corresponds to the lower pole of the curve and arises when the cephalo-trochanteric line is perpendicular to the direction of the muscle; the force is greatest in the highest and lowest positions of the tip of the great trochanter, that is to say on either side of the lower pole of the curve. Since the position of the greater trochanter is, in practice, always lower, it can be said that, as a general rule, angulation into varus diminishes the tension of the gluteus medius whilst angulation into valgus increases it. However, contrary to current opinion, the effect produced on the force applied by the gluteus medius is not proportional to the ammount of varisization. The effectiveness of a varisization is greater the more the hip is in valgus and there is a critical zone with increasing varus where the effect becomes minimal. Displacement of the femoral shaft (McMurray's operation) has little effect. In Chiari's operation, diminution of the ilio-trochanteric angle and shortening of the medial lever with lengthening of the lateral lever by medial transposition of the point of application of the femoral head diminishes the force required of the gluteus medius very effectively. In particular, the effect of Chiari's operation is greater when the hip is displaced or there is coxa valga. The method described allows a precise calculation to be made on a tracing of the patient's radiograph of the effect to the proposed operation on the force required by the gluteus medius. The different parameters could be applied to a computer and thus allows statistical definition of anthropometric date concerning the force of contraction of the gluteus medius."} {"id": "PMID:152950", "title": "[The measurement of the tibial tuberosity. Patella groove distanced technique and results (author's transl)].", "content": "The line between the summit of the tibial tuberosity and the bottom of the trochlea groove as seen on a radiograph taken with the knee in 30 degrees of flexion and neutral rotation is indicative of the valgus position of the quadriceps mechanism at the moment of engatement of the patella in the groove. The authors stress the technical requirements to obtain the radiograph which permits this measurement. Measurement of a group of normal knees and of two groups of knees presenting with known patello-femoral pathology (lateral patello-femoral arthrosis and current dislocation of the patella) are given. In the study of distrubance of the patello-femoral articulation, this measurement provides information of theoretical and therapeutic interest.", "contents": "[The measurement of the tibial tuberosity. Patella groove distanced technique and results (author's transl)]. The line between the summit of the tibial tuberosity and the bottom of the trochlea groove as seen on a radiograph taken with the knee in 30 degrees of flexion and neutral rotation is indicative of the valgus position of the quadriceps mechanism at the moment of engatement of the patella in the groove. The authors stress the technical requirements to obtain the radiograph which permits this measurement. Measurement of a group of normal knees and of two groups of knees presenting with known patello-femoral pathology (lateral patello-femoral arthrosis and current dislocation of the patella) are given. In the study of distrubance of the patello-femoral articulation, this measurement provides information of theoretical and therapeutic interest."} {"id": "PMID:152954", "title": "[The fixation of madreporic total hip prosthesis; an experimental study (author's transl)].", "content": "The author has designed a new type of total hip prosthesis described as \"madreporic\" because its surface is rough and resembles some kinds of coral. This type of implant, which does not require cement, was tested on dogs. The bone-prosthesis junction was assessed using light and electron microscopy. Radio-spectrography and micro-radiography showed that osteogenesis occurred in the roughened surface of the implant leading to an early, strong and long-standing fixation. The prosthesis was inserted in two hundred patients. Five were removed after septic complications and one after premature death. The fixation with new bone to the surface of the metal was confirmed.", "contents": "[The fixation of madreporic total hip prosthesis; an experimental study (author's transl)]. The author has designed a new type of total hip prosthesis described as \"madreporic\" because its surface is rough and resembles some kinds of coral. This type of implant, which does not require cement, was tested on dogs. The bone-prosthesis junction was assessed using light and electron microscopy. Radio-spectrography and micro-radiography showed that osteogenesis occurred in the roughened surface of the implant leading to an early, strong and long-standing fixation. The prosthesis was inserted in two hundred patients. Five were removed after septic complications and one after premature death. The fixation with new bone to the surface of the metal was confirmed."} {"id": "PMID:152955", "title": "[Spine deformity in Marfan's syndrome in childhood (author's transl)].", "content": "The authors have studied twenty cases of spine deformity in children suffering from Marfan's syndrome. They describe the main features of the disease and point out the difficulty of accurate diagnosis in children with minor involvement. The deformities are those of a dysplastic scoliosis as shown by the frequency of vertebral inversion on the lateral view: dorso-lumbar kyphosis, decreased lumbar lordosis. The treatment should be surgical because of the danger of a fatal outcome without treatment. The incidence of non-union is high and the authors recommend systematic revision of the fusion double curve scolioses with a moderate kyphosis. In cases of severe kyphosis, the addition of anterior grafting is recommended.", "contents": "[Spine deformity in Marfan's syndrome in childhood (author's transl)]. The authors have studied twenty cases of spine deformity in children suffering from Marfan's syndrome. They describe the main features of the disease and point out the difficulty of accurate diagnosis in children with minor involvement. The deformities are those of a dysplastic scoliosis as shown by the frequency of vertebral inversion on the lateral view: dorso-lumbar kyphosis, decreased lumbar lordosis. The treatment should be surgical because of the danger of a fatal outcome without treatment. The incidence of non-union is high and the authors recommend systematic revision of the fusion double curve scolioses with a moderate kyphosis. In cases of severe kyphosis, the addition of anterior grafting is recommended."} {"id": "PMID:152956", "title": "[The incidence of progressive scoliosis and kyphosis after fractures and dislocations of the spine in children (author's transl)].", "content": "The authors have observed forty-two cases of fractures and dislocations of the spine in children. In twenty-eight cases there was a complete spinal cord lesion and in four cases a partial cord lesion with some recovery. Ten children had no neurological lesion. Fifteen progressive kyphoses and twenty-two progressive scolioses were noted and analysed. The kyphotic deformities were more severe at cervical levels and seem to be aggravated by laminectomies. They were stabilised at the time of bone maturity. To prevent this deformity, the authors recommend long-term plaster cast immobilisation associated with posterior fusion. In scoliotic deformities, the authors distinguish those due to neurological involvement and those arising at the level of the fracture due to disturbance of vertebral growth. Indications for treatment are discussed in relation to the age of the patient and the level of the fracture.", "contents": "[The incidence of progressive scoliosis and kyphosis after fractures and dislocations of the spine in children (author's transl)]. The authors have observed forty-two cases of fractures and dislocations of the spine in children. In twenty-eight cases there was a complete spinal cord lesion and in four cases a partial cord lesion with some recovery. Ten children had no neurological lesion. Fifteen progressive kyphoses and twenty-two progressive scolioses were noted and analysed. The kyphotic deformities were more severe at cervical levels and seem to be aggravated by laminectomies. They were stabilised at the time of bone maturity. To prevent this deformity, the authors recommend long-term plaster cast immobilisation associated with posterior fusion. In scoliotic deformities, the authors distinguish those due to neurological involvement and those arising at the level of the fracture due to disturbance of vertebral growth. Indications for treatment are discussed in relation to the age of the patient and the level of the fracture."} {"id": "PMID:152957", "title": "[Non-articular fractures of the proximal tibia (author's transl)].", "content": "The authors have made a detailed study of the bony architecture of the upper tibial metaphysis and epiphysis. They describe a number of types of extra-articular fracture of the upper end of the tibia according to their mechanical etiology (direct injury or strain). Forty five such fractures are reviewed. Forty percent of the fractures were compound and vascular complications occurred in three cases. Two patients died from embolism and one required early amputation. Twenty seven patients were treated conservatively and eighteen surgically. After an analysis of the results, the authors note that bonyunion is particularly slow in this type of fracture. They conclude that surgical treatment gives better results, especially with the use of epiphyseal plates.", "contents": "[Non-articular fractures of the proximal tibia (author's transl)]. The authors have made a detailed study of the bony architecture of the upper tibial metaphysis and epiphysis. They describe a number of types of extra-articular fracture of the upper end of the tibia according to their mechanical etiology (direct injury or strain). Forty five such fractures are reviewed. Forty percent of the fractures were compound and vascular complications occurred in three cases. Two patients died from embolism and one required early amputation. Twenty seven patients were treated conservatively and eighteen surgically. After an analysis of the results, the authors note that bonyunion is particularly slow in this type of fracture. They conclude that surgical treatment gives better results, especially with the use of epiphyseal plates."} {"id": "PMID:152958", "title": "[Cylindrical osteotomy of the upper end of the tibia [author's transl)].", "content": "The authors describe a modification of the original technique of Blaimont and Maquet. Cylindrical osteotomy allows correction of deformity in the frontal plane (genu varum or valgum) with forward displacement of the tibial tuberosity. The technique and instruments are described. The osteotomy is fixed by screws and joint mobilisation is begun after two weeks. Thirty patients have been operated on. The results are described as satisfactory.", "contents": "[Cylindrical osteotomy of the upper end of the tibia [author's transl)]. The authors describe a modification of the original technique of Blaimont and Maquet. Cylindrical osteotomy allows correction of deformity in the frontal plane (genu varum or valgum) with forward displacement of the tibial tuberosity. The technique and instruments are described. The osteotomy is fixed by screws and joint mobilisation is begun after two weeks. Thirty patients have been operated on. The results are described as satisfactory."} {"id": "PMID:152961", "title": "The response of Suffolk lambs to an escalating experimental infection with Dictyocaulus filaria.", "content": "Infection of Suffolk lambs with Dictyocaulus filaria larvae beginning at two months of age with one larva per day, six days per week, and doubling every four weeks to reach a final infection rate of 64 larvae per day gave rise to a pattern of larval excretion in the faeces which approximated to that seen in naturally infected Suffolk lambs in Midlothian in 1974. Several of the lambs were still infected with adult D filaria and were excreting larvae in their faeces 28 weeks after the infection began. However, when some of the lambs were challenged at this time, those which had received the previous escalating infection were resistant to the challenge infection.", "contents": "The response of Suffolk lambs to an escalating experimental infection with Dictyocaulus filaria. Infection of Suffolk lambs with Dictyocaulus filaria larvae beginning at two months of age with one larva per day, six days per week, and doubling every four weeks to reach a final infection rate of 64 larvae per day gave rise to a pattern of larval excretion in the faeces which approximated to that seen in naturally infected Suffolk lambs in Midlothian in 1974. Several of the lambs were still infected with adult D filaria and were excreting larvae in their faeces 28 weeks after the infection began. However, when some of the lambs were challenged at this time, those which had received the previous escalating infection were resistant to the challenge infection."} {"id": "PMID:152967", "title": "A critique of some of the current concepts on the immunopathogenesis of rheumatoid arthritis.", "content": "The interaction of polycations produced during tissue damage and C-reactive protein, and the enzymatic degradation of complement components may be positive mechanisms augmenting immune-complex/complement damage, while reduced phagocytosis and reduced chemotaxis may be negative mechanisms. In cell-mediated immunity, systems consisting of C-reactive protein, proteases, prostaglandins and immune complexes are all potentially capable of negative feedback control.", "contents": "A critique of some of the current concepts on the immunopathogenesis of rheumatoid arthritis. The interaction of polycations produced during tissue damage and C-reactive protein, and the enzymatic degradation of complement components may be positive mechanisms augmenting immune-complex/complement damage, while reduced phagocytosis and reduced chemotaxis may be negative mechanisms. In cell-mediated immunity, systems consisting of C-reactive protein, proteases, prostaglandins and immune complexes are all potentially capable of negative feedback control."} {"id": "PMID:152969", "title": "[Subcutaneous silicone gel prosthese (author's transl)].", "content": "The use of silicone implants to correct an acquired or congenital abnormality of the face involves the use of:--blocks of foam, though these retract and the volume implanted must therefore be overestimated.--compact blocks of elastomer, which tend to migrate and to produce inaesthetic bumps with disturbances in the vascularisation of the skin. The authors therefore had the idea of making \"to measure\" implants similar to breast implants: envelope of silicone elastomer enclosing a gel of chosen viscosity, absorbing forces applied to the envelope and therefore tending to prevent migration of the implant. The latter has dacron patches to facilitate its adherence to deep layers. This description of manufacturing methods and operative techniques, despite a short follow-up, reports encouraging results from which it is possible to determine the indications of this type of procedure.", "contents": "[Subcutaneous silicone gel prosthese (author's transl)]. The use of silicone implants to correct an acquired or congenital abnormality of the face involves the use of:--blocks of foam, though these retract and the volume implanted must therefore be overestimated.--compact blocks of elastomer, which tend to migrate and to produce inaesthetic bumps with disturbances in the vascularisation of the skin. The authors therefore had the idea of making \"to measure\" implants similar to breast implants: envelope of silicone elastomer enclosing a gel of chosen viscosity, absorbing forces applied to the envelope and therefore tending to prevent migration of the implant. The latter has dacron patches to facilitate its adherence to deep layers. This description of manufacturing methods and operative techniques, despite a short follow-up, reports encouraging results from which it is possible to determine the indications of this type of procedure."} {"id": "PMID:152971", "title": "Alloantigen-induced enhancement and suppression of human cytotoxic lymphocyte responses to autologous lymphoblastoid cell lines.", "content": "In vitro sensitization of human lymphocytes to autologous lymphoblastoid cell lines (LCL) has been shown to give rise to cytotoxic lymphocytes capable of lysing autologous as well as allogeneic LCL cells. However, allogeneic LCL cells were found to be markedly less effective than autologous LCL cells in terms of generating lymphocytes capable of lysing autologous LCL cells. The addition of allogeneic LCL cells or allogeneic normal lymphocytes to a mixture of responding lymphocytes and X-irradiated autologous LCL cells suppressed the generation of cytotoxic lymphocytes against autologous LCL cells. Furthermore, suppressor T cells generated in allogeneic mixed leucocyte culture (MLC) and supernatants from MLC likewise decreased the generation of cytotoxic lymphocytes to X-irradiated autologous LCL cells. In contrast to the findings that alloantigens suppress the generation of cytotoxicity of X-irradiated autologous LCL cells, which ordinarily induce strong cytotoxic responses, were the findings that allogeneic stimulating cells and supernatants from MLC enhanced cytotoxic responses to autologous ultraviolet light or extensively heat-treated LCL cells that induce weaker cytotoxic responses. The possible mechanisms whereby alloantigens enhance or suppress cytotoxic responses to autologous abnormal cells and the implications of these findings are discussed.", "contents": "Alloantigen-induced enhancement and suppression of human cytotoxic lymphocyte responses to autologous lymphoblastoid cell lines. In vitro sensitization of human lymphocytes to autologous lymphoblastoid cell lines (LCL) has been shown to give rise to cytotoxic lymphocytes capable of lysing autologous as well as allogeneic LCL cells. However, allogeneic LCL cells were found to be markedly less effective than autologous LCL cells in terms of generating lymphocytes capable of lysing autologous LCL cells. The addition of allogeneic LCL cells or allogeneic normal lymphocytes to a mixture of responding lymphocytes and X-irradiated autologous LCL cells suppressed the generation of cytotoxic lymphocytes against autologous LCL cells. Furthermore, suppressor T cells generated in allogeneic mixed leucocyte culture (MLC) and supernatants from MLC likewise decreased the generation of cytotoxic lymphocytes to X-irradiated autologous LCL cells. In contrast to the findings that alloantigens suppress the generation of cytotoxicity of X-irradiated autologous LCL cells, which ordinarily induce strong cytotoxic responses, were the findings that allogeneic stimulating cells and supernatants from MLC enhanced cytotoxic responses to autologous ultraviolet light or extensively heat-treated LCL cells that induce weaker cytotoxic responses. The possible mechanisms whereby alloantigens enhance or suppress cytotoxic responses to autologous abnormal cells and the implications of these findings are discussed."} {"id": "PMID:152972", "title": "Work and disability at the age of 30 years. A sociomedical study of a birth-cohort from Bergen. III. Disability as related to medical, psychological and educational background.", "content": "This article deals with occupational disability at the age of 30 years, seen the light of medical, psychological and educational background. The study is based on a cohort of 1570 persons, all live births in 1940 of mothers then residing in Bergen. This birth-cohort was followed-up in the compulsory school system at age 14 years, and again at age 30 years, concluding at 1st June 1971. Only those of the cohort residing in Norway on 1st June 1971, a total of 1331 persons, are included in the present analysis. The diagnoses discussed are based on data obtained from disability pension case records, from the National Insurance Institution files and from the Public Welfare office files. Results of medical and psychological examinations made on a stratified random sample of the cohort are also used. Thirty-seven persons (2.8%) of the total of 1331 were found to be disabled according to the criteria set for this study. The prevailing primary diagnosis was mental disorder, as 25 of the disabled had this diagnosis, oligophrenia being dominant. The former pupils in the different types of compulsory school attended at age 14 years show a frequency of disability at age 30 years as follows: junior high school 0.8%, continuation school 1.3%, elementary school classes for slow learners 10.7%, special schools for the educable mentally retarded 32.7%, and receiving services for the mentally retarded, 97.0%.", "contents": "Work and disability at the age of 30 years. A sociomedical study of a birth-cohort from Bergen. III. Disability as related to medical, psychological and educational background. This article deals with occupational disability at the age of 30 years, seen the light of medical, psychological and educational background. The study is based on a cohort of 1570 persons, all live births in 1940 of mothers then residing in Bergen. This birth-cohort was followed-up in the compulsory school system at age 14 years, and again at age 30 years, concluding at 1st June 1971. Only those of the cohort residing in Norway on 1st June 1971, a total of 1331 persons, are included in the present analysis. The diagnoses discussed are based on data obtained from disability pension case records, from the National Insurance Institution files and from the Public Welfare office files. Results of medical and psychological examinations made on a stratified random sample of the cohort are also used. Thirty-seven persons (2.8%) of the total of 1331 were found to be disabled according to the criteria set for this study. The prevailing primary diagnosis was mental disorder, as 25 of the disabled had this diagnosis, oligophrenia being dominant. The former pupils in the different types of compulsory school attended at age 14 years show a frequency of disability at age 30 years as follows: junior high school 0.8%, continuation school 1.3%, elementary school classes for slow learners 10.7%, special schools for the educable mentally retarded 32.7%, and receiving services for the mentally retarded, 97.0%."} {"id": "PMID:152973", "title": "Immediate and late results of aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve.", "content": "Single aortic valve replacement was performed in 110 patients at Ullev\u00e5l Hospital, Oslo, between 1971 and 1976. The follow-up period was 1 to 6 years (mean 31 months). The early postoperative mortality was 6.3% and the late mortality 8.2%. Postoperatively 44% of the surviving patients were in the N.Y.H.A. functional class I and 55% in class II, while 71% of the patients were in class III or IV pre-operatively. Objective evidence of improvement was shown by reduction in mean heart volume from 610 ml/m2 pre-operatively to 512 ml/m2 postoperatively (p less than 0.001). Electrocardiographic signs of left ventricular hypertrophy, measured as the combined voltage of Smax and Rmax in V1 to V6, were 56mV pre-operatively and 42 mV postoperatively (p less than 0.001). Myocardial failure was the main cause of death postoperatively. Sudden death occurred in 5 of the 9 patients in the late mortality group. Old age at the time of operation (65 to 71 years) was not associated with increased risk of death and complications, while alcoholism did increase the mortality rate.", "contents": "Immediate and late results of aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve. Single aortic valve replacement was performed in 110 patients at Ullev\u00e5l Hospital, Oslo, between 1971 and 1976. The follow-up period was 1 to 6 years (mean 31 months). The early postoperative mortality was 6.3% and the late mortality 8.2%. Postoperatively 44% of the surviving patients were in the N.Y.H.A. functional class I and 55% in class II, while 71% of the patients were in class III or IV pre-operatively. Objective evidence of improvement was shown by reduction in mean heart volume from 610 ml/m2 pre-operatively to 512 ml/m2 postoperatively (p less than 0.001). Electrocardiographic signs of left ventricular hypertrophy, measured as the combined voltage of Smax and Rmax in V1 to V6, were 56mV pre-operatively and 42 mV postoperatively (p less than 0.001). Myocardial failure was the main cause of death postoperatively. Sudden death occurred in 5 of the 9 patients in the late mortality group. Old age at the time of operation (65 to 71 years) was not associated with increased risk of death and complications, while alcoholism did increase the mortality rate."} {"id": "PMID:152979", "title": "Tubal patency: hysterosalpingography compared with laparoscopy.", "content": "Laparoscopy was done about three months after hysterosalpingography (HSG) in 121 patients complaining of infertility. Normal patency was found with both technics in 71 patients (58.6%). In 23 of the 97 patients with a normal HSG, however, peritubal or tubal disease was observed at the time of laparoscopy (false-negative results, 19%). Twenty-four tubal obstructions (19.8%) were detected by HSG (16 distal and eight proximal) but five distal and four proximal obstructions were not confirmed by laparoscopy (false-positive results, 7.4%). In addition, laparoscopic evaluation demonstrated endometriosis in 31 cases, polycystic ovaries in six, and uterine fibroids in five.", "contents": "Tubal patency: hysterosalpingography compared with laparoscopy. Laparoscopy was done about three months after hysterosalpingography (HSG) in 121 patients complaining of infertility. Normal patency was found with both technics in 71 patients (58.6%). In 23 of the 97 patients with a normal HSG, however, peritubal or tubal disease was observed at the time of laparoscopy (false-negative results, 19%). Twenty-four tubal obstructions (19.8%) were detected by HSG (16 distal and eight proximal) but five distal and four proximal obstructions were not confirmed by laparoscopy (false-positive results, 7.4%). In addition, laparoscopic evaluation demonstrated endometriosis in 31 cases, polycystic ovaries in six, and uterine fibroids in five."} {"id": "PMID:153003", "title": "Pathogenesis of aortoduodenal fistula: experimental and clinical correlates.", "content": "An aortoduodenal fistula (ADF) is believed to stem from erosion of a rigid prosthesis into the fixed retroperitoneal duodenum. Experimental and clinical data do not support a mechanical etiology, but indicate that the pathogenesis is an unrecognized graft infection with pseudoaneurysm formation. A 5 cm segment of Dacron was interposed in the infrarenal aortas of 24 dogs that were divided into four groups of six animals each. In group 1 (control) the duodenum was fixed by sutures to the proximal anastomosis of the Dacron graft. At 6 weeks' follow-up, no ADFs or deaths had occurred among this group. In group 2 the duodenum was fixed to the aortoprosthetic anastomosis and the dogs received an intravenous infusion of 10(8) S. aureus; two of these dogs developed ADF (P less than 0.01). In group 3 the duodenum was incorporated as a patch on the anterior aspect of the aortoprosthetic suture line, creating a false aneurysm; three of these animals died as a result of ADF. A false aneurysm was created in group 4 dogs, as in group 3, but in addition, 10(8) S. aureus was administered intravenously; here five to six animals developed ADF. Clinical and bacteriological evidence of graft infection was present in seven of 11 patients with ADF who were seen over an 18 year period. Five had pseudoaneurysm formation at the proximal anastomosis. Operation was performed in eight patients; three had closure of the aortic leak and repair of the duodenum with omentum interposition. All resulted in recurrent fistula and delayed hemorrhage. Simple graft excision in two patients without reconstitution of peripheral circulation resulted in lower extremity gangrene. The three survivors had graft excision and axillofemoral bypass. These data suggest that the etiology of ADF is primary low-grade infection. Successful operation necessitates excision of the graft, duodenal closure, and an extraanatomical axillofemoral bypass graft.", "contents": "Pathogenesis of aortoduodenal fistula: experimental and clinical correlates. An aortoduodenal fistula (ADF) is believed to stem from erosion of a rigid prosthesis into the fixed retroperitoneal duodenum. Experimental and clinical data do not support a mechanical etiology, but indicate that the pathogenesis is an unrecognized graft infection with pseudoaneurysm formation. A 5 cm segment of Dacron was interposed in the infrarenal aortas of 24 dogs that were divided into four groups of six animals each. In group 1 (control) the duodenum was fixed by sutures to the proximal anastomosis of the Dacron graft. At 6 weeks' follow-up, no ADFs or deaths had occurred among this group. In group 2 the duodenum was fixed to the aortoprosthetic anastomosis and the dogs received an intravenous infusion of 10(8) S. aureus; two of these dogs developed ADF (P less than 0.01). In group 3 the duodenum was incorporated as a patch on the anterior aspect of the aortoprosthetic suture line, creating a false aneurysm; three of these animals died as a result of ADF. A false aneurysm was created in group 4 dogs, as in group 3, but in addition, 10(8) S. aureus was administered intravenously; here five to six animals developed ADF. Clinical and bacteriological evidence of graft infection was present in seven of 11 patients with ADF who were seen over an 18 year period. Five had pseudoaneurysm formation at the proximal anastomosis. Operation was performed in eight patients; three had closure of the aortic leak and repair of the duodenum with omentum interposition. All resulted in recurrent fistula and delayed hemorrhage. Simple graft excision in two patients without reconstitution of peripheral circulation resulted in lower extremity gangrene. The three survivors had graft excision and axillofemoral bypass. These data suggest that the etiology of ADF is primary low-grade infection. Successful operation necessitates excision of the graft, duodenal closure, and an extraanatomical axillofemoral bypass graft."} {"id": "PMID:153004", "title": "Our fibrinolytic potential.", "content": "Several methods of determining fibrinolytic activity were explored. The methods which gave the most satisfactory appraisal of the amount of fibrinolysin administered were as follows: euglobulin fraction on a prepared fibrin clot; euglobulin fraction method on benzoylarginine methyl ester; whole blood clot spontaneous lysis method. At present, the first of these three methods is the technique of choice. A preparation devised to observe the lysis of blood clots in vivo under the action of human fibrinolysin is described. In this preparation the successful lysis of fresh blood clots produced experimentally in segments of autogenous veins anastomosed to arteries was observed. The administration of plasmin by aerosol was followed by an increased lytic activity of the plasma of premature infants. Six patients in whom the clinical diagnosis of pulmonary hyaline membrane was made recovered completely after the treatment with human plasmin by aerosol. Forty-three percent of the children with the same diagnosis in whom plasmin was not used died (control subjects). Large doses of human fibrinolysin administered by the intravenous route prevented the formation of peritoneal adhesions in 100% of the animals treated. Adhesions developed in all of the dogs in which the intraperitoneal route was used. Fibrinolytic activity in the peripheral blood was increased considerably in all of the animals in which adhesions did not develop. No hemorrhagic phenomena other than slight oozing of the wounds were observed.", "contents": "Our fibrinolytic potential. Several methods of determining fibrinolytic activity were explored. The methods which gave the most satisfactory appraisal of the amount of fibrinolysin administered were as follows: euglobulin fraction on a prepared fibrin clot; euglobulin fraction method on benzoylarginine methyl ester; whole blood clot spontaneous lysis method. At present, the first of these three methods is the technique of choice. A preparation devised to observe the lysis of blood clots in vivo under the action of human fibrinolysin is described. In this preparation the successful lysis of fresh blood clots produced experimentally in segments of autogenous veins anastomosed to arteries was observed. The administration of plasmin by aerosol was followed by an increased lytic activity of the plasma of premature infants. Six patients in whom the clinical diagnosis of pulmonary hyaline membrane was made recovered completely after the treatment with human plasmin by aerosol. Forty-three percent of the children with the same diagnosis in whom plasmin was not used died (control subjects). Large doses of human fibrinolysin administered by the intravenous route prevented the formation of peritoneal adhesions in 100% of the animals treated. Adhesions developed in all of the dogs in which the intraperitoneal route was used. Fibrinolytic activity in the peripheral blood was increased considerably in all of the animals in which adhesions did not develop. No hemorrhagic phenomena other than slight oozing of the wounds were observed."} {"id": "PMID:153014", "title": "Improved synthesis of 16alpha-hydroxylated androgens: intermediates of estriol formation in pregnancy.", "content": "16alpha-Hydroxyandrostenedione (16alpha-hydroxyandrost-4-ene-3,17-dione), 16alpha-hydroxytestosterone (16alpha,17beta-dihydroxyandrost-4-en-3-one) and 16alpha-hydroxydehydroepiandrosterone 3-sulfate (3beta, 16alpha-dihydroxyandrost-5-en-17-one 3-monosulfate) were synthesized by a new chemical approach with much improved yield. 16alpha-Bromoandrostendione was converted to the hydrazone of 16alpha-hydroxyandrostenedione which gave 16alpha-hydroxyandrostenedione on acid hydrolysis in total 63% yield. Oxidation of 16alpha-hydroxydehydroepiandrosterone with Jones' reagent also selectively afforded 16alpha-hydroxyandrostenedione. 16alpha-Hydroxytestosterone was observed by selective reduction of 16alpha-hydroxyandrostenedione with sodium borohydride. Reaction of 16alpha-hydroxydehydroepiandrosterone with chlorosulfonic acid in pyridine selectively gave the 3-monosulfate. The structure of the sulfate was deduced from its solvolysis to the starting material, and its acetylation and subsequent solvolysis to 16alpha-hydroxydehydroepiandrosterone 16-acetate. All procedures are suitable for large scale synthesis without the use of microorganisms.", "contents": "Improved synthesis of 16alpha-hydroxylated androgens: intermediates of estriol formation in pregnancy. 16alpha-Hydroxyandrostenedione (16alpha-hydroxyandrost-4-ene-3,17-dione), 16alpha-hydroxytestosterone (16alpha,17beta-dihydroxyandrost-4-en-3-one) and 16alpha-hydroxydehydroepiandrosterone 3-sulfate (3beta, 16alpha-dihydroxyandrost-5-en-17-one 3-monosulfate) were synthesized by a new chemical approach with much improved yield. 16alpha-Bromoandrostendione was converted to the hydrazone of 16alpha-hydroxyandrostenedione which gave 16alpha-hydroxyandrostenedione on acid hydrolysis in total 63% yield. Oxidation of 16alpha-hydroxydehydroepiandrosterone with Jones' reagent also selectively afforded 16alpha-hydroxyandrostenedione. 16alpha-Hydroxytestosterone was observed by selective reduction of 16alpha-hydroxyandrostenedione with sodium borohydride. Reaction of 16alpha-hydroxydehydroepiandrosterone with chlorosulfonic acid in pyridine selectively gave the 3-monosulfate. The structure of the sulfate was deduced from its solvolysis to the starting material, and its acetylation and subsequent solvolysis to 16alpha-hydroxydehydroepiandrosterone 16-acetate. All procedures are suitable for large scale synthesis without the use of microorganisms."} {"id": "PMID:153023", "title": "[Physiological polymorphism in a population of the common frog. I. The polymorphism of a population of the common frog for the trait of muscle tissue heat resistance].", "content": "A study was made of heat resistance (36+/-0.2 degrees C) of m. interphalangealis of the third finger of a hind extremity in animals of one population of Rana temporaria L. living on the boundary between Leningrad region and Pskov region. Within this population, the existence of three groups of individuals differing in heat resistance levels of their m. interphalangealis is postulated. This conclusion is based on the distribution curve of heat resistance values and on the application of the probit-method. The distribution of the frequency of occurrence of individuals in these three groups follows Hardy-Weinberg's equation.", "contents": "[Physiological polymorphism in a population of the common frog. I. The polymorphism of a population of the common frog for the trait of muscle tissue heat resistance]. A study was made of heat resistance (36+/-0.2 degrees C) of m. interphalangealis of the third finger of a hind extremity in animals of one population of Rana temporaria L. living on the boundary between Leningrad region and Pskov region. Within this population, the existence of three groups of individuals differing in heat resistance levels of their m. interphalangealis is postulated. This conclusion is based on the distribution curve of heat resistance values and on the application of the probit-method. The distribution of the frequency of occurrence of individuals in these three groups follows Hardy-Weinberg's equation."} {"id": "PMID:153024", "title": "[Physiological polymorphism of a population of the common frog. II. The polymorphism of the type of muscle tissue heat resistance in stress].", "content": "A study was made of the dynamics in the heat resistance of m. interphalangealis of individual grass frogs under stress. The response of muscle tissue to injury can be differentiated into three types according to the initial heat resistance level: increase, decrease and phase change of the resistance. The pattern of response of muscle tissue of individual frogs to stress is one of manifestationss of physiological polymorphism of the population.", "contents": "[Physiological polymorphism of a population of the common frog. II. The polymorphism of the type of muscle tissue heat resistance in stress]. A study was made of the dynamics in the heat resistance of m. interphalangealis of individual grass frogs under stress. The response of muscle tissue to injury can be differentiated into three types according to the initial heat resistance level: increase, decrease and phase change of the resistance. The pattern of response of muscle tissue of individual frogs to stress is one of manifestationss of physiological polymorphism of the population."} {"id": "PMID:153025", "title": "[Effect of the central cholinolytic, cyclosil, on the ultrastructure and functional characteristics of rat liver mitochondria].", "content": "The influence of central cholinolytic cyclosil on the oxidative phosphorilation, ATPase activity and ultrastructure of hepatic mitochondria has been studied. The increased effectivity of mitochondrial macroergic compounds formation in the presence of cyclosil (0.04 mg/ml) was noticed. The oxygen consumption rate of these particles did not change. These findings and the electron microscopic observations on mitochondrial swelling in the presence of the cholinolytic agent suggest that cyclosil enchances the degree of mitochondrial energization.", "contents": "[Effect of the central cholinolytic, cyclosil, on the ultrastructure and functional characteristics of rat liver mitochondria]. The influence of central cholinolytic cyclosil on the oxidative phosphorilation, ATPase activity and ultrastructure of hepatic mitochondria has been studied. The increased effectivity of mitochondrial macroergic compounds formation in the presence of cyclosil (0.04 mg/ml) was noticed. The oxygen consumption rate of these particles did not change. These findings and the electron microscopic observations on mitochondrial swelling in the presence of the cholinolytic agent suggest that cyclosil enchances the degree of mitochondrial energization."} {"id": "PMID:153026", "title": "[Electrophoretic studies of acid mucopolysaccharides in skin, prekeratin of hair follicles and in keratoses of wool].", "content": "Mucopolysaccharide complex isolated from skin, prekeratin of hair follicles and keratoses of wool by paper electrophoresis was separated into chondroitin sulphate and hyaluronic acid. The content of chondroitin sulphate in all the objects under investigation except for gamma-keratosis is higher than that of hyaluronic acid. The highest level of chondroitin-sulphuric acid is observed in the matrix of prekeratin of hair follicles and cuticule of wood fibre, i. e. beta-keratosis.", "contents": "[Electrophoretic studies of acid mucopolysaccharides in skin, prekeratin of hair follicles and in keratoses of wool]. Mucopolysaccharide complex isolated from skin, prekeratin of hair follicles and keratoses of wool by paper electrophoresis was separated into chondroitin sulphate and hyaluronic acid. The content of chondroitin sulphate in all the objects under investigation except for gamma-keratosis is higher than that of hyaluronic acid. The highest level of chondroitin-sulphuric acid is observed in the matrix of prekeratin of hair follicles and cuticule of wood fibre, i. e. beta-keratosis."} {"id": "PMID:153027", "title": "[Low temperature effects on sarcoplasmic reticulum membrane permeability for Ca2+].", "content": "The effect of rapid freezing down to--196 degree C was studied as applied to the functional activity of sarcoplasmic reticulum (SR) membranes Ca2+-pump. It is found that the SR Ca-transport system is damaged under the effect of low temperatures: the transport activity of Ca ions across the reticulum membrane is reduced simultaneously with a slight increase in the ATPase activity. The rate of Ca ions accumulation by SR vesicles decreases and the magnitude of Ca: ATP ratio is reduced. The damage of the SR membrane Ca-transport system after freezing is related to an increase in the rate of the accumulated Ca2+ rapid leak from the vesicles through the system of active transport at the moment of ATPase \"work\" and to an increase in the rate of passive diffusion.", "contents": "[Low temperature effects on sarcoplasmic reticulum membrane permeability for Ca2+]. The effect of rapid freezing down to--196 degree C was studied as applied to the functional activity of sarcoplasmic reticulum (SR) membranes Ca2+-pump. It is found that the SR Ca-transport system is damaged under the effect of low temperatures: the transport activity of Ca ions across the reticulum membrane is reduced simultaneously with a slight increase in the ATPase activity. The rate of Ca ions accumulation by SR vesicles decreases and the magnitude of Ca: ATP ratio is reduced. The damage of the SR membrane Ca-transport system after freezing is related to an increase in the rate of the accumulated Ca2+ rapid leak from the vesicles through the system of active transport at the moment of ATPase \"work\" and to an increase in the rate of passive diffusion."} {"id": "PMID:153030", "title": "Togavirus-like particles in renal epithelium of patients with systemic lupus erythematosus.", "content": "Virus-like particles, about 45 nm in diameter, were present in renal epithelium (tubules and podocytes) of 12 patients with confirmed systemic lupus erythematosus (SLE) and in 2 patients with probable SLE. They were not detected in renal biopsies from non-SLE patients. Morphologically, they suggest togavirus-like particles.", "contents": "Togavirus-like particles in renal epithelium of patients with systemic lupus erythematosus. Virus-like particles, about 45 nm in diameter, were present in renal epithelium (tubules and podocytes) of 12 patients with confirmed systemic lupus erythematosus (SLE) and in 2 patients with probable SLE. They were not detected in renal biopsies from non-SLE patients. Morphologically, they suggest togavirus-like particles."} {"id": "PMID:153028", "title": "[Effect of substances inhibiting the ion transport on Mg2+, Ca2+-ATPase activity of synaptic plasma membranes].", "content": "The Mg2+, Ca2+-ATPase activity of plasma membranes in bull brain synaptosomas was studied as affected by ruthenium red, hexamine cobalt, aminazine, verapamyl, melipramin, lanthanum acetate and oligomycin. Lanthanum acetate in a concentration of 5.10(-5)M is shown to inhibit completely the enzyme activity. Ruthenium red and hexamine cobalt in a concentration of 10(-4) inhibit this ATPase activity by 50-60%. Melipramin, aminazine, verapamyl in concentrations of 10(-6)-10(-4)M and oligomycin in a concentration of 0.01-5 microgram/ml have no effect on the enzyme activity.", "contents": "[Effect of substances inhibiting the ion transport on Mg2+, Ca2+-ATPase activity of synaptic plasma membranes]. The Mg2+, Ca2+-ATPase activity of plasma membranes in bull brain synaptosomas was studied as affected by ruthenium red, hexamine cobalt, aminazine, verapamyl, melipramin, lanthanum acetate and oligomycin. Lanthanum acetate in a concentration of 5.10(-5)M is shown to inhibit completely the enzyme activity. Ruthenium red and hexamine cobalt in a concentration of 10(-4) inhibit this ATPase activity by 50-60%. Melipramin, aminazine, verapamyl in concentrations of 10(-6)-10(-4)M and oligomycin in a concentration of 0.01-5 microgram/ml have no effect on the enzyme activity."} {"id": "PMID:153031", "title": "[Ultrastructural morphometric analysis of normally loaded human myocardial left ventricles from young and old patients (author's transl)].", "content": "An ultrastructural and morphometric analysis was performed on human myocardial left ventricle, obtained during surgical heart operations on normally loaded ventricles. The diagnoses of the patients were a) Persistant foramen ovale b) Atrial septal defect stage (I.-II) c) Mitral stenosis (stage III.-IV.). The median values of left ventricular pressure were not pathologically elevated. The patients were divided in 2 groups, the younger one ranging from 5-15 years, the older from 42-78 years. It was shown that the volume density of the interstitial tissue does not differ with the aging process. The number of the nuclei per test area of the heart muscle cells decreased within age (P less than 0.001). This finding suggests a decreasing process in the number of the heart muscle cells and an increase in size of the individual myocardial cell. Increase in the volume density of myofibrils was demonstrated at electron microscopical level with aging (P less than 0.02). The volume density of mitochondria is the same in both groups, whereas the volume density of the remaining cytoplasm (without myofibrils and mitochondria) decreases (P less than 0.05). The numberical density of the mitochondria increased in the older patient group (P less than 0.001).", "contents": "[Ultrastructural morphometric analysis of normally loaded human myocardial left ventricles from young and old patients (author's transl)]. An ultrastructural and morphometric analysis was performed on human myocardial left ventricle, obtained during surgical heart operations on normally loaded ventricles. The diagnoses of the patients were a) Persistant foramen ovale b) Atrial septal defect stage (I.-II) c) Mitral stenosis (stage III.-IV.). The median values of left ventricular pressure were not pathologically elevated. The patients were divided in 2 groups, the younger one ranging from 5-15 years, the older from 42-78 years. It was shown that the volume density of the interstitial tissue does not differ with the aging process. The number of the nuclei per test area of the heart muscle cells decreased within age (P less than 0.001). This finding suggests a decreasing process in the number of the heart muscle cells and an increase in size of the individual myocardial cell. Increase in the volume density of myofibrils was demonstrated at electron microscopical level with aging (P less than 0.02). The volume density of mitochondria is the same in both groups, whereas the volume density of the remaining cytoplasm (without myofibrils and mitochondria) decreases (P less than 0.05). The numberical density of the mitochondria increased in the older patient group (P less than 0.001)."} {"id": "PMID:153032", "title": "[Ultrastructural morphometric analysis of hypertrophied human myocardial left ventricles (author's transl)].", "content": "Biopsies of hypertrophied human myocardial left ventricles were investigated morphometrically. The diagnoses of the patients were stenosis of the aortic valve, aortic insufficiency or a combination of both lesions. The results were compared with those from normally loaded human left ventricles. There are no differences on light microscopical level between the volume densities of interstitial tissue and of heart muscle cells in the three groups of patients. A significant diminution of the volume density of the nuclei (P less than 0.001) and the number of nuclei per test area (P less than 0.001) when compared with normal groups suggests an increase in volume of the single heart muscle cell. The ultrastructural study shows marked increase in volume density of myofibrils (P less than 0.0001), with accompanying decrease in the volume densities of mitochondria (P less than 0.0001) and the remaining cytoplasm (P less than 0.001). A gross decrease in the surface area of mitochondria (P less than 0.001) and of cristae mitochondriales (P less than 0.0001) is found. The morphological equivalents of this result are numerous stages of mithochondrial destruction including cristolysis. All myocardial weights were beyond the \"critical heart weight\".", "contents": "[Ultrastructural morphometric analysis of hypertrophied human myocardial left ventricles (author's transl)]. Biopsies of hypertrophied human myocardial left ventricles were investigated morphometrically. The diagnoses of the patients were stenosis of the aortic valve, aortic insufficiency or a combination of both lesions. The results were compared with those from normally loaded human left ventricles. There are no differences on light microscopical level between the volume densities of interstitial tissue and of heart muscle cells in the three groups of patients. A significant diminution of the volume density of the nuclei (P less than 0.001) and the number of nuclei per test area (P less than 0.001) when compared with normal groups suggests an increase in volume of the single heart muscle cell. The ultrastructural study shows marked increase in volume density of myofibrils (P less than 0.0001), with accompanying decrease in the volume densities of mitochondria (P less than 0.0001) and the remaining cytoplasm (P less than 0.001). A gross decrease in the surface area of mitochondria (P less than 0.001) and of cristae mitochondriales (P less than 0.0001) is found. The morphological equivalents of this result are numerous stages of mithochondrial destruction including cristolysis. All myocardial weights were beyond the \"critical heart weight\"."} {"id": "PMID:153033", "title": "The relaxation of sarcomeres in ischemic injury of myocardium.", "content": "Polarization-microscopic and micrometric investigations of the myocardium during infarction at autopsy and in experimental ischemic conditions, has shown that one of the earliest and most typical morphological signs of ischemic myocardium is sarcomere relaxation. The latter is expressed by the loss of contractility of muscle cells in life time and in strongly frozen corpses, and due to the effects of fixatives. Increase of the percentage of relaxed sarcomeres parallels the duration of experimental ischemia and the time after myocardial infarction. This allows the indirect calculation of irreversible cell change.", "contents": "The relaxation of sarcomeres in ischemic injury of myocardium. Polarization-microscopic and micrometric investigations of the myocardium during infarction at autopsy and in experimental ischemic conditions, has shown that one of the earliest and most typical morphological signs of ischemic myocardium is sarcomere relaxation. The latter is expressed by the loss of contractility of muscle cells in life time and in strongly frozen corpses, and due to the effects of fixatives. Increase of the percentage of relaxed sarcomeres parallels the duration of experimental ischemia and the time after myocardial infarction. This allows the indirect calculation of irreversible cell change."} {"id": "PMID:153034", "title": "The regional registry of gastro-intestinal cancer North Baden (2.2 million inhabitants).", "content": "The advantages of a population-based registry are discussed. It is shown that a registry for gastro-intestinal cancer in a district with expert medical care based upon histo-pathological diagnosis, has the principal advantage that it limits the sites of material collection to a few effective contributors, thus providing highly accurate data. The disadvantage of collecting data by two separate steps should be tolerated. The geographic situation and the organization of the regional registry for gastro-intestinal cancer in North Baden are described and the incidences for these cancers for the years 1971-1975 are given for the population of 2.2 million.", "contents": "The regional registry of gastro-intestinal cancer North Baden (2.2 million inhabitants). The advantages of a population-based registry are discussed. It is shown that a registry for gastro-intestinal cancer in a district with expert medical care based upon histo-pathological diagnosis, has the principal advantage that it limits the sites of material collection to a few effective contributors, thus providing highly accurate data. The disadvantage of collecting data by two separate steps should be tolerated. The geographic situation and the organization of the regional registry for gastro-intestinal cancer in North Baden are described and the incidences for these cancers for the years 1971-1975 are given for the population of 2.2 million."} {"id": "PMID:153035", "title": "[Incidence and post-mortem frequency of malignant tumors of the stomach, colon, rectum, and lung (author's transl)].", "content": "A method for determining the incidence of malignancies of the stomach, colon, rectum, and lungs has been based on the frequency of the tumors in the autopsy material of the Institute of Pathology of the University of Heidelberg for the period 1900 to 1975. The main goal of this model is time independent selection of autopsy material indicated by an almost constant pattern for sex, average age at death, number of inhabitants, and number of autopsies. There is a relationship between incidence and autopsy frequency only when coding the diagnoses independently of their contributions to the cause of death. The results show a nearly constant incidence of stomach cancer, a steady incidence of colon and rectal cancer which, however, differs for men and women, and a large increase in the incidence of lung cancer.", "contents": "[Incidence and post-mortem frequency of malignant tumors of the stomach, colon, rectum, and lung (author's transl)]. A method for determining the incidence of malignancies of the stomach, colon, rectum, and lungs has been based on the frequency of the tumors in the autopsy material of the Institute of Pathology of the University of Heidelberg for the period 1900 to 1975. The main goal of this model is time independent selection of autopsy material indicated by an almost constant pattern for sex, average age at death, number of inhabitants, and number of autopsies. There is a relationship between incidence and autopsy frequency only when coding the diagnoses independently of their contributions to the cause of death. The results show a nearly constant incidence of stomach cancer, a steady incidence of colon and rectal cancer which, however, differs for men and women, and a large increase in the incidence of lung cancer."} {"id": "PMID:153036", "title": "Extent and level of fascial involvement in 100 cases with nodular fasciitis.", "content": "Nodular fasciitis (NF) shows a cellular proliferation which leads to widening of the fascia. Frequently unilateral or more often bilateral disruption of the fascia, with an infiltrative pattern is present. Subcutaneous fascia and surrounding fat are involved. Superficially the cellular proliferation may extend into dermal connective tissue. Deeper muscular tissue may be involved, with transitional forms or purely intramuscular changes, compatible with proliferative myositis. Proliferative myositis is considered to be a deep-seated variant of NF with muscular involvement. Intramuscular myxoma may be thought of as an intramuscular and mucoid variant of NF. A bilateral infiltrative pattern was most frequently found at all levels; in cases with muscular involvement it was always present.", "contents": "Extent and level of fascial involvement in 100 cases with nodular fasciitis. Nodular fasciitis (NF) shows a cellular proliferation which leads to widening of the fascia. Frequently unilateral or more often bilateral disruption of the fascia, with an infiltrative pattern is present. Subcutaneous fascia and surrounding fat are involved. Superficially the cellular proliferation may extend into dermal connective tissue. Deeper muscular tissue may be involved, with transitional forms or purely intramuscular changes, compatible with proliferative myositis. Proliferative myositis is considered to be a deep-seated variant of NF with muscular involvement. Intramuscular myxoma may be thought of as an intramuscular and mucoid variant of NF. A bilateral infiltrative pattern was most frequently found at all levels; in cases with muscular involvement it was always present."} {"id": "PMID:153040", "title": "[The so-called cardiac myxoma. Histological, electron microscopical, immunofluorescence, and biochemical investigations in 3 cases (author's transl)].", "content": "Three cardiac Myxomas were studied by light-, immuno-fluorescence and electron microscopy. Acid mucopolysaccharides of the tumour were isolated chromatographically. The surfaces of the \"myxomas\" were papillary in two cases and smooth in one. The smooth surfaced tumour recurred six months after primary resection; histological specimens were more cellular than those of the papillary tumors and showed nuclear polymorphism and mitoses. The cells of two papillary tumours were identified as endocardial by electron microscopy, however, the cells of the smooth surfaced tumour were typical myofibroblasts. In both types of \"myxomas\" the cells were rich on cytoplasmic filament that contained acto-myosin. Biochemical investigation failed to reveal any difference between the acid mucopolysaccharide pattern of the two tumour types; isolated mucopolysaccharides being typical for embryonal mesenchymal tissue. The authors agree with Albertini (1963), that \"cardiac myxoma\" is a misnomer for two different typical endocardial tumours: a true endothelioma and a \"special fibroma\" (myofibroma or myofibrosarcoma).", "contents": "[The so-called cardiac myxoma. Histological, electron microscopical, immunofluorescence, and biochemical investigations in 3 cases (author's transl)]. Three cardiac Myxomas were studied by light-, immuno-fluorescence and electron microscopy. Acid mucopolysaccharides of the tumour were isolated chromatographically. The surfaces of the \"myxomas\" were papillary in two cases and smooth in one. The smooth surfaced tumour recurred six months after primary resection; histological specimens were more cellular than those of the papillary tumors and showed nuclear polymorphism and mitoses. The cells of two papillary tumours were identified as endocardial by electron microscopy, however, the cells of the smooth surfaced tumour were typical myofibroblasts. In both types of \"myxomas\" the cells were rich on cytoplasmic filament that contained acto-myosin. Biochemical investigation failed to reveal any difference between the acid mucopolysaccharide pattern of the two tumour types; isolated mucopolysaccharides being typical for embryonal mesenchymal tissue. The authors agree with Albertini (1963), that \"cardiac myxoma\" is a misnomer for two different typical endocardial tumours: a true endothelioma and a \"special fibroma\" (myofibroma or myofibrosarcoma)."} {"id": "PMID:153042", "title": "Ultrastructural aspects of bubble formation in human fatal accidents after exposure to compressed air.", "content": "Electron microscopic investigations were performed on samples of human tissue obtained from subjects following fatal decompression sickness, associated with hyperbaric air-therapy. Intra- and extracellular gas bubbles of varying size were identified throughout the entire body. Each bubble was covered by an osmiophilic non-homogeneous coat of cloudy and flocculent material, native to its specific locality. This envelope measured from 30 to 560 Angstroem-units in thickness. Association of this covering with an electrokinetic zonal activity, detected biophysically by Lee and Hairston (1971) is assumed. We consider this surface coat prevents nitrogen from being eliminated via the blood-lung barrier.", "contents": "Ultrastructural aspects of bubble formation in human fatal accidents after exposure to compressed air. Electron microscopic investigations were performed on samples of human tissue obtained from subjects following fatal decompression sickness, associated with hyperbaric air-therapy. Intra- and extracellular gas bubbles of varying size were identified throughout the entire body. Each bubble was covered by an osmiophilic non-homogeneous coat of cloudy and flocculent material, native to its specific locality. This envelope measured from 30 to 560 Angstroem-units in thickness. Association of this covering with an electrokinetic zonal activity, detected biophysically by Lee and Hairston (1971) is assumed. We consider this surface coat prevents nitrogen from being eliminated via the blood-lung barrier."} {"id": "PMID:153043", "title": "Pressure-flow relationships and pathological changes during renal preservation.", "content": "The renal pedicle of one kidney from each of four dogs was ligated for one hour. The contralateral kidney served as a control. Both kidneys were removed and perfused using the \"Belzer\" technique. Pressure-flow relationships were determined and biopsy samples taken. The vasculature was then injected with silicone rubber. Perfusion resistance, vascular filling with silicone rubber and observations made by electron microscopy were compared.", "contents": "Pressure-flow relationships and pathological changes during renal preservation. The renal pedicle of one kidney from each of four dogs was ligated for one hour. The contralateral kidney served as a control. Both kidneys were removed and perfused using the \"Belzer\" technique. Pressure-flow relationships were determined and biopsy samples taken. The vasculature was then injected with silicone rubber. Perfusion resistance, vascular filling with silicone rubber and observations made by electron microscopy were compared."} {"id": "PMID:153045", "title": "Aberrant subclavian artery (arteria lusoria): sex differences in the prevalence of various forms of the malformation. Evaluation of 1378 observations.", "content": "43 original and 1335 previously published observations of aberrant subclavian artery (A. lusoria) were analyzed. The sex distribution varied for different types of the malformation: females predominated over males in instances of right aberrant subclavian artery and if pre-stenotic A. lusoria was combined with coarctation of the aorta. Male predominance was found in cases of combination of post-stenotic A. lusoria with coarctation and of aberrant left subclavian artery. An equal sex distribution was observed for A. lusoria combined with interruption of the aortic arch. Clinical, pathological and embryological aspects of the condition are discussed.", "contents": "Aberrant subclavian artery (arteria lusoria): sex differences in the prevalence of various forms of the malformation. Evaluation of 1378 observations. 43 original and 1335 previously published observations of aberrant subclavian artery (A. lusoria) were analyzed. The sex distribution varied for different types of the malformation: females predominated over males in instances of right aberrant subclavian artery and if pre-stenotic A. lusoria was combined with coarctation of the aorta. Male predominance was found in cases of combination of post-stenotic A. lusoria with coarctation and of aberrant left subclavian artery. An equal sex distribution was observed for A. lusoria combined with interruption of the aortic arch. Clinical, pathological and embryological aspects of the condition are discussed."} {"id": "PMID:153046", "title": "Psammoma bodies in meningioma. Appearance by scanning electron microscopy.", "content": "Psammoma bodies from eight memingiomas have been examined by both light and scanning electron microscopy (SEM). The bodies are primarily composed of calcium apatite which is deposited within a nidus of tightly laminated collagen fibers.", "contents": "Psammoma bodies in meningioma. Appearance by scanning electron microscopy. Psammoma bodies from eight memingiomas have been examined by both light and scanning electron microscopy (SEM). The bodies are primarily composed of calcium apatite which is deposited within a nidus of tightly laminated collagen fibers."} {"id": "PMID:153048", "title": "Eosinophilic pancreatitis in the newborn infant of a diabetic mother.", "content": "The authors have studied the pancreas of a premature female infant born to a diabetic mother. The findings included a peri-insular eosinophilic leucocyte infiltration, macropolinesia and a marked increase in B cells. In the exocrime parenchyma small B cells aggregates were also observed. B cells contained voluminous hypercromatic muclei and degranulated cytoplasm. Morphometric data demonstrated an increase in islet tissue. These morphological findings are indicative of excessive insulin secretion. The presence of eosinophilic leucocytes in pancreatic tissue and the pathogenic mechanism involved are discussed.", "contents": "Eosinophilic pancreatitis in the newborn infant of a diabetic mother. The authors have studied the pancreas of a premature female infant born to a diabetic mother. The findings included a peri-insular eosinophilic leucocyte infiltration, macropolinesia and a marked increase in B cells. In the exocrime parenchyma small B cells aggregates were also observed. B cells contained voluminous hypercromatic muclei and degranulated cytoplasm. Morphometric data demonstrated an increase in islet tissue. These morphological findings are indicative of excessive insulin secretion. The presence of eosinophilic leucocytes in pancreatic tissue and the pathogenic mechanism involved are discussed."} {"id": "PMID:153049", "title": "Sternberg-Reed cells with intracytoplasmic lymphocytes. Phagocytosis or emperipolesis?", "content": "Phagocytosis by Sternberg-Reed cells is a rare phenomenon. A case of nodular sclerosis type of Hodgkin's disease with large numbers of apparently vital lymphocytes in the cytoplasm of the Sternberg-Reed cells is described in this paper. The question whether this feature is the result of phagocytosis or emperipolesis is discussed.", "contents": "Sternberg-Reed cells with intracytoplasmic lymphocytes. Phagocytosis or emperipolesis? Phagocytosis by Sternberg-Reed cells is a rare phenomenon. A case of nodular sclerosis type of Hodgkin's disease with large numbers of apparently vital lymphocytes in the cytoplasm of the Sternberg-Reed cells is described in this paper. The question whether this feature is the result of phagocytosis or emperipolesis is discussed."} {"id": "PMID:153061", "title": "Increased aryl hydrocarbon hydroxylase activity in hepatic microsomes from streptozotocin-diabetic female rats.", "content": "In streptozotocin-induced diabetic male rats, hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity was depressed to less than control values, but was increased in microsomes from diabetic female rats. Insulin treatment of diabetic animals returned the altered AHH activity to control values in both sexes of rats. 2. Hepatic microsomal AHH activity was increased over control values in both sexes of diabetic mice. 3. Protection of female rats from the diabetogenic effects of streptozotocin by nicotinamide pretreatment also prevented the increase in AHH activity observed in unprotected animals. 4. Treatment of control and diabetic female rats with 3-methylcholanthrene resulted in larger increases in hepatic AHH activity in control animals, but similar increases in cytochrome P-448 content occurred in both treatment groups. 5. Differential stimulatory or inhibitory effects on AHH activity were observed after the addition of SKF 525-A, metyrapone, and rotenone to hepatic microsomes in vitro from control and diabetic female rats. However, similar stimulatory responses in AHH activity were observed after addition of alpha-naphthoflavone to microsomes from both treatment groups.", "contents": "Increased aryl hydrocarbon hydroxylase activity in hepatic microsomes from streptozotocin-diabetic female rats. In streptozotocin-induced diabetic male rats, hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity was depressed to less than control values, but was increased in microsomes from diabetic female rats. Insulin treatment of diabetic animals returned the altered AHH activity to control values in both sexes of rats. 2. Hepatic microsomal AHH activity was increased over control values in both sexes of diabetic mice. 3. Protection of female rats from the diabetogenic effects of streptozotocin by nicotinamide pretreatment also prevented the increase in AHH activity observed in unprotected animals. 4. Treatment of control and diabetic female rats with 3-methylcholanthrene resulted in larger increases in hepatic AHH activity in control animals, but similar increases in cytochrome P-448 content occurred in both treatment groups. 5. Differential stimulatory or inhibitory effects on AHH activity were observed after the addition of SKF 525-A, metyrapone, and rotenone to hepatic microsomes in vitro from control and diabetic female rats. However, similar stimulatory responses in AHH activity were observed after addition of alpha-naphthoflavone to microsomes from both treatment groups."} {"id": "PMID:153062", "title": "[Determination of the sensitivity of mycobacteria to pyrazinamide and nicotinamide (author's transl)].", "content": "Since pyrazinamide (PZA) has had a come-back in therapy of tuberculosis a simple and reliable method for sensitivity tests has been necessary. A comparison of resistance tests to PZA in acid L\u00f6wenstein-Jensen-medium and in fluid medium with those to nicotinamide (NSA) showed a clear superiority of the NSA method, recommended by BRANDER. Also in routine sensitivity tests the use of NSA instead of PZA has stood the test. Another advantage of the method is the possibility to integrate it in the simplified proportion method without any additional work.", "contents": "[Determination of the sensitivity of mycobacteria to pyrazinamide and nicotinamide (author's transl)]. Since pyrazinamide (PZA) has had a come-back in therapy of tuberculosis a simple and reliable method for sensitivity tests has been necessary. A comparison of resistance tests to PZA in acid L\u00f6wenstein-Jensen-medium and in fluid medium with those to nicotinamide (NSA) showed a clear superiority of the NSA method, recommended by BRANDER. Also in routine sensitivity tests the use of NSA instead of PZA has stood the test. Another advantage of the method is the possibility to integrate it in the simplified proportion method without any additional work."} {"id": "PMID:153063", "title": "[Sociologic studies in acne vulgaris. 1. Disease significance of acne vulgaris].", "content": "A questionnaire was presented to 2009 18--19 year old military recruitment candidates which enabled assessment of antipathy towards patients with severe acne vulgaris, the occupational handicap associated with severe acne and subjective inhibitions in acne patients. In addition, these persons were examined clinically with regard to presence of acne vulgaris. Finally, the level of education of the persons questioned was determined. The investigations show that severe acne has an appreciable disease rating. This results from antipathy of other people, the occupational inpediment and the psychological inhibitions of the acne patient. This disease rating appears to be objectively greater the lower the level of education of the acne patient. The disease rating does not appear to be entirely clear to the acne patient with a low level of education.", "contents": "[Sociologic studies in acne vulgaris. 1. Disease significance of acne vulgaris]. A questionnaire was presented to 2009 18--19 year old military recruitment candidates which enabled assessment of antipathy towards patients with severe acne vulgaris, the occupational handicap associated with severe acne and subjective inhibitions in acne patients. In addition, these persons were examined clinically with regard to presence of acne vulgaris. Finally, the level of education of the persons questioned was determined. The investigations show that severe acne has an appreciable disease rating. This results from antipathy of other people, the occupational inpediment and the psychological inhibitions of the acne patient. This disease rating appears to be objectively greater the lower the level of education of the acne patient. The disease rating does not appear to be entirely clear to the acne patient with a low level of education."} {"id": "PMID:153064", "title": "The change in carcinogenic effectiveness of some cyclic nitrosamines at different doses.", "content": "The carcinogenic effectiveness in rats of three cyclic nitrosamines administered at two doses separated by a factor of five has been studied. All three compounds showed a response at the lower dose quite different from that at the higher dose. One, 2,6-dimethyl-dinitrosopiperazine, was only a little less effective at the lower dose than at the higher dose, giving 100% nasal turbinate tumors, but only 33% esophageal tumors, compared with 100% esophageal tumors at the higher dose. 3,4-Dichloronitrosopiperidine gave 100% incidence of esophageal tumors at the higher dose. At the lower dose, survival of the rats was very much better, some living 80 weeks, and, in addition to the esophagus, there were tumors of several organs including forestomach, tongue, and nasal turbinates. On the other hand, 2,6-dimethylnitrosomorpholine was a very much weaker carcinogen at the lower than at the higher dose, only six animals dying with tumors, compared with 100% incidence at the higher dose. However, the pattern of mortality of rats given the lower dose of dimethylnitrosomorpholine was similar to that of rats given the lower dose of dichloronitrosopiperidine.", "contents": "The change in carcinogenic effectiveness of some cyclic nitrosamines at different doses. The carcinogenic effectiveness in rats of three cyclic nitrosamines administered at two doses separated by a factor of five has been studied. All three compounds showed a response at the lower dose quite different from that at the higher dose. One, 2,6-dimethyl-dinitrosopiperazine, was only a little less effective at the lower dose than at the higher dose, giving 100% nasal turbinate tumors, but only 33% esophageal tumors, compared with 100% esophageal tumors at the higher dose. 3,4-Dichloronitrosopiperidine gave 100% incidence of esophageal tumors at the higher dose. At the lower dose, survival of the rats was very much better, some living 80 weeks, and, in addition to the esophagus, there were tumors of several organs including forestomach, tongue, and nasal turbinates. On the other hand, 2,6-dimethylnitrosomorpholine was a very much weaker carcinogen at the lower than at the higher dose, only six animals dying with tumors, compared with 100% incidence at the higher dose. However, the pattern of mortality of rats given the lower dose of dimethylnitrosomorpholine was similar to that of rats given the lower dose of dichloronitrosopiperidine."} {"id": "PMID:153065", "title": "Nitrate nitrogen levels in drinking water of urban areas with high- and low-risk populations for stomach cancer: an environmental epidemiology study.", "content": "A correlation study between mean nitrate nitrogen levels (ppm) in drinking water samples (N = 1389) of Chilean urban areas and age-adjusted death rates per 100 000 population from stomach cancer, by province or region and sex, was made. Drinking water samples from all provinces (N = 25) had a weighed mean of 1.446 ppm (S.E.M. 0.068) with a range of 0.00--30.00 ppm. Nitrate nigrogen levels showed a positive but not significant association with male death rates. The correlation coefficient was +0.0335. Similarly, such levels did exhibit a positive but not significant correlation with female death rates (r = +0.0486). When NO3-N levels and male (r = +0.1367) or female (r = +0.1143) death rates were studied, by region, positive but insignificant correlations were detected. Using Cochran's approximation, mean nitrate nitrogen levels in drinking water samples from six provinces with 50% of the Chilean population (period 1953--55 versus 1973--75), showed a decrease from 1.835 to 1.291 ppm, but there was no significant difference (t = 1.32) between the two values, except in samples from Santiago Province (t = 2.11, P less than 0.05). Provinces (south central area) showing the highest gastric cancer mortality rates in the world for females (up to 40.8/100,000), and ranking second for males (up to 84.1/100,000), exhibited a very low mean level (0.825 ppm).", "contents": "Nitrate nitrogen levels in drinking water of urban areas with high- and low-risk populations for stomach cancer: an environmental epidemiology study. A correlation study between mean nitrate nitrogen levels (ppm) in drinking water samples (N = 1389) of Chilean urban areas and age-adjusted death rates per 100 000 population from stomach cancer, by province or region and sex, was made. Drinking water samples from all provinces (N = 25) had a weighed mean of 1.446 ppm (S.E.M. 0.068) with a range of 0.00--30.00 ppm. Nitrate nigrogen levels showed a positive but not significant association with male death rates. The correlation coefficient was +0.0335. Similarly, such levels did exhibit a positive but not significant correlation with female death rates (r = +0.0486). When NO3-N levels and male (r = +0.1367) or female (r = +0.1143) death rates were studied, by region, positive but insignificant correlations were detected. Using Cochran's approximation, mean nitrate nitrogen levels in drinking water samples from six provinces with 50% of the Chilean population (period 1953--55 versus 1973--75), showed a decrease from 1.835 to 1.291 ppm, but there was no significant difference (t = 1.32) between the two values, except in samples from Santiago Province (t = 2.11, P less than 0.05). Provinces (south central area) showing the highest gastric cancer mortality rates in the world for females (up to 40.8/100,000), and ranking second for males (up to 84.1/100,000), exhibited a very low mean level (0.825 ppm)."} {"id": "PMID:153066", "title": "[Change of toxicity and carcinogenicity of n-methyl-n-nitrosobenzylamine in rats by methylsubstitution at the c-atoms adjacent to nitrogen (author's transl)].", "content": "Substitution with a methyl group at the C-atoms adjacent to nitrogen of N-nitroso-N-methylbenzylamine (NMBA) results in a considerable reduction LD 50: N-nitroso-N-methylbenzylamine : 18 mg/kg (Druckrey et al., 1967) N-nitroso-N-methyl-(1-phenyl)-ethylamine (I) : 600 mg/kg N-nitroso-N-methyl-2-(2-phenyl)-propylamine (II) : 2100 mg/kg N-nitroso-N-ethyl-benzylamine (III) : 250 mg/kg Substitution with a methyl group at the methylene of the moiety of NMBA (NMPEA I) reduces also the carcinogenic activity, but it produces in all animals carcinomas of the oesophagus and the pharynx; the replacement of both H-atoms by methyl groups (NMPPA, II) causes under the condition chosen no development of tumors, because for the activation step no proton is available. The exchange of N-methyl by N-ethyl of NMBA (NEBA, III) however produces no change in the carcinogenicity.", "contents": "[Change of toxicity and carcinogenicity of n-methyl-n-nitrosobenzylamine in rats by methylsubstitution at the c-atoms adjacent to nitrogen (author's transl)]. Substitution with a methyl group at the C-atoms adjacent to nitrogen of N-nitroso-N-methylbenzylamine (NMBA) results in a considerable reduction LD 50: N-nitroso-N-methylbenzylamine : 18 mg/kg (Druckrey et al., 1967) N-nitroso-N-methyl-(1-phenyl)-ethylamine (I) : 600 mg/kg N-nitroso-N-methyl-2-(2-phenyl)-propylamine (II) : 2100 mg/kg N-nitroso-N-ethyl-benzylamine (III) : 250 mg/kg Substitution with a methyl group at the methylene of the moiety of NMBA (NMPEA I) reduces also the carcinogenic activity, but it produces in all animals carcinomas of the oesophagus and the pharynx; the replacement of both H-atoms by methyl groups (NMPPA, II) causes under the condition chosen no development of tumors, because for the activation step no proton is available. The exchange of N-methyl by N-ethyl of NMBA (NEBA, III) however produces no change in the carcinogenicity."} {"id": "PMID:153067", "title": "The fine structure of monoclonal Hodgkin cells cultured in diffusion chambers.", "content": "Pleural effusion cells from two patients with stage IV Hodgkin's disease have been cultured continuously in diffusion chambers in mice and studied by electron microscopy after a culture period exceeding 100 days. Cell identity and monoclonal growth in culture has been documented by marker chromosomes (Hossfeld and Schmidt, 1978). These cultured cells grow in close connection, projecting pseudopode-like processes into the intercellular spaces. Most nuclei are lobulated. They always are of low electron density with a norrow rim of condensed chromatin confined to the nuclear membrane. One large prominent nucleolus and up to four smaller nucleoli are found. Nuclear pockets in case 1 and deep cytoplasmic invaginations into the nuclear area in both cases frequently occur. In the cytoplasm, besides microtubuli and fibrils, the Golgi apparatus and mitochondria are the predominant organelles. Most mitochondria appear to be dilated containing fragmented cristae. Free ribosomes and polysomal aggregates are randomly distributed. The ratio nucleoplasm:cytoplasm, on the average, is 0.7 in both cases and the cell diameters lie distinctly above those of lymphocytes. At the electron microscope level these cultured monoclonal cells of Hodgkin's disease are not distinguishable from those described in genuine Hodgkin material. Their probable origin and apparent relation to true histiocytic lymphoma cells will be discussed.", "contents": "The fine structure of monoclonal Hodgkin cells cultured in diffusion chambers. Pleural effusion cells from two patients with stage IV Hodgkin's disease have been cultured continuously in diffusion chambers in mice and studied by electron microscopy after a culture period exceeding 100 days. Cell identity and monoclonal growth in culture has been documented by marker chromosomes (Hossfeld and Schmidt, 1978). These cultured cells grow in close connection, projecting pseudopode-like processes into the intercellular spaces. Most nuclei are lobulated. They always are of low electron density with a norrow rim of condensed chromatin confined to the nuclear membrane. One large prominent nucleolus and up to four smaller nucleoli are found. Nuclear pockets in case 1 and deep cytoplasmic invaginations into the nuclear area in both cases frequently occur. In the cytoplasm, besides microtubuli and fibrils, the Golgi apparatus and mitochondria are the predominant organelles. Most mitochondria appear to be dilated containing fragmented cristae. Free ribosomes and polysomal aggregates are randomly distributed. The ratio nucleoplasm:cytoplasm, on the average, is 0.7 in both cases and the cell diameters lie distinctly above those of lymphocytes. At the electron microscope level these cultured monoclonal cells of Hodgkin's disease are not distinguishable from those described in genuine Hodgkin material. Their probable origin and apparent relation to true histiocytic lymphoma cells will be discussed."} {"id": "PMID:153068", "title": "Effect of splenectomy on B- and T-lymphocytes and a benzpyrene-induced murine sarcoma.", "content": "The investigation of 400 adult mice had the objective to find out 1. The influence of splenectomy on genesis and growth of a benzpyrene-induced sarcoma and 2. The behavior of B- and T-lymphocytes under the influence of splenectomy. 1. A significantly lower number of tumors developed in splenectomized animals (28.5%) as compared to controls (49.5%). 2. A significant decrease of B-lymphocytes and an increase in T cells after splenectomy were found in the peripheral blood. 3. The examination of the tumor marginal zone showed a decreased number of B-lymphocytes and an increase of T-lymphocytes, while the total count of round cells remained unchanged. These results are discussed and compared with results of other authors.", "contents": "Effect of splenectomy on B- and T-lymphocytes and a benzpyrene-induced murine sarcoma. The investigation of 400 adult mice had the objective to find out 1. The influence of splenectomy on genesis and growth of a benzpyrene-induced sarcoma and 2. The behavior of B- and T-lymphocytes under the influence of splenectomy. 1. A significantly lower number of tumors developed in splenectomized animals (28.5%) as compared to controls (49.5%). 2. A significant decrease of B-lymphocytes and an increase in T cells after splenectomy were found in the peripheral blood. 3. The examination of the tumor marginal zone showed a decreased number of B-lymphocytes and an increase of T-lymphocytes, while the total count of round cells remained unchanged. These results are discussed and compared with results of other authors."} {"id": "PMID:153069", "title": "Release of glycolytic enzymes from cultivated tumor cells.", "content": "Several types of cultured cells release glycolytic enzymes into their suspending medium. This effect is most obvious with tumor cells, especially with their ascites forms. Erythrocytes do not release glycolytic enzymes. The total extracellular phosphoglucose isomerase activity consists of two components. One part is dissolved in the medium, the other one is sedimentable at 150 X g together with the cells. The latter seems to be localized at the cell surface. At densities of about 10(6) cells/ml maximum activity in the medium is reached within 5--10 min. After that no further release of enzyme activity can be observed. Serum reduces the rate of enzyme release considerably. This effect can be reversed by washing with protein free media. Treatment with trypsin leads to high extracellular phosphoglucose isomerase activities of the cells which originally show low external enzyme activity. Erythrocytes do not show any effect with trypsin, ascites tumor cells do not alter their high extracellular enzyme activity. At a density of 10(5) cells/ml, Yoshida acites tumor cells, cultured in vitro, release about 12% of originally intracellular phosphoglucose isomerase activity by 5 elutions with fresh medium. The process of enzyme release shows a certain selectivity in respect to different glycolytic enzymes. Aldolase exhibits the highest activity in the medium in relation to its homogenate activity.", "contents": "Release of glycolytic enzymes from cultivated tumor cells. Several types of cultured cells release glycolytic enzymes into their suspending medium. This effect is most obvious with tumor cells, especially with their ascites forms. Erythrocytes do not release glycolytic enzymes. The total extracellular phosphoglucose isomerase activity consists of two components. One part is dissolved in the medium, the other one is sedimentable at 150 X g together with the cells. The latter seems to be localized at the cell surface. At densities of about 10(6) cells/ml maximum activity in the medium is reached within 5--10 min. After that no further release of enzyme activity can be observed. Serum reduces the rate of enzyme release considerably. This effect can be reversed by washing with protein free media. Treatment with trypsin leads to high extracellular phosphoglucose isomerase activities of the cells which originally show low external enzyme activity. Erythrocytes do not show any effect with trypsin, ascites tumor cells do not alter their high extracellular enzyme activity. At a density of 10(5) cells/ml, Yoshida acites tumor cells, cultured in vitro, release about 12% of originally intracellular phosphoglucose isomerase activity by 5 elutions with fresh medium. The process of enzyme release shows a certain selectivity in respect to different glycolytic enzymes. Aldolase exhibits the highest activity in the medium in relation to its homogenate activity."} {"id": "PMID:153070", "title": "Microangiopathic haemolytic anaemia in cancer patients with bone marrow infiltration.", "content": "Eight patients suffering from wide-spread malignancies presented with a severe microangiopathic haemolytic anaemia (MHA) without gross evidence for coagulation abnormalities. The common feature in these patients was bone marrow infiltration with malignant cells, suggesting a pathogenic link between bone marrow carcinosis and red cell destruction. Furthermore, it is concluded that MHA is a rare complication of malignancy and a terminal syndrome rather than an early manifestation of the disease.", "contents": "Microangiopathic haemolytic anaemia in cancer patients with bone marrow infiltration. Eight patients suffering from wide-spread malignancies presented with a severe microangiopathic haemolytic anaemia (MHA) without gross evidence for coagulation abnormalities. The common feature in these patients was bone marrow infiltration with malignant cells, suggesting a pathogenic link between bone marrow carcinosis and red cell destruction. Furthermore, it is concluded that MHA is a rare complication of malignancy and a terminal syndrome rather than an early manifestation of the disease."} {"id": "PMID:153071", "title": "In vitro studies of human breast carcinoma cells obtained by aspiration biopsy.", "content": "Cells from 14 human breast carcinoma were obtained by aspiration biopsy and used for in vitro cultivation. Growth could be observed in three cultures, which were derived from solid, partly adenoid growing tumors with metastases in the axillary nodes. The growth started after 2--6 days in culture and lasted 2--4 weeks. No permanent line could be established.", "contents": "In vitro studies of human breast carcinoma cells obtained by aspiration biopsy. Cells from 14 human breast carcinoma were obtained by aspiration biopsy and used for in vitro cultivation. Growth could be observed in three cultures, which were derived from solid, partly adenoid growing tumors with metastases in the axillary nodes. The growth started after 2--6 days in culture and lasted 2--4 weeks. No permanent line could be established."} {"id": "PMID:153072", "title": "The ultrastructural differentiation of synaptic sites in the inner plexiform layer of a teleostean retina.", "content": "The differentiation of axon terminals in the retina inner plexiform layer was studied by electron microscopy, with special reference to synaptic junctions, number and size of synaptic vesicles, dense core vesicles, biogenic amines and ATPase. Five types of synaptic junctions were found, including a ribbon type. They appear on different days of embryonic life and show different patterns of increase. The ultrastructural differentiation of the most frequent type is described in detail. The numbers of synaptic vesicles indicate the existence of three types of axon terminals which appear on different days. These and other data lead to the following model: The contacts between amacrine cells are the first to appear, followed by amacrine--bipolar cell contacts and amacrine--ganglion cell contacts. The latter are the most frequent ones and increase immediately after having appeared, while amacrine--bipolar cell contacts increase only some days later, which is also the case for bipolar--amacrine cell contacts. Biogenic amines and cytochemically detectable ATPase appear along with the formation of synaptic sites.", "contents": "The ultrastructural differentiation of synaptic sites in the inner plexiform layer of a teleostean retina. The differentiation of axon terminals in the retina inner plexiform layer was studied by electron microscopy, with special reference to synaptic junctions, number and size of synaptic vesicles, dense core vesicles, biogenic amines and ATPase. Five types of synaptic junctions were found, including a ribbon type. They appear on different days of embryonic life and show different patterns of increase. The ultrastructural differentiation of the most frequent type is described in detail. The numbers of synaptic vesicles indicate the existence of three types of axon terminals which appear on different days. These and other data lead to the following model: The contacts between amacrine cells are the first to appear, followed by amacrine--bipolar cell contacts and amacrine--ganglion cell contacts. The latter are the most frequent ones and increase immediately after having appeared, while amacrine--bipolar cell contacts increase only some days later, which is also the case for bipolar--amacrine cell contacts. Biogenic amines and cytochemically detectable ATPase appear along with the formation of synaptic sites."} {"id": "PMID:153074", "title": "[Experimental studies of the distribution of intravenously injected iodine-labeled cytonal (diethylstilbestrol diphosphate)].", "content": "After intravenous injection the distribution of iodine-labelled diethylstilbestral-diphosphate (cytonal) was investigated in various organs of the rat. For this purpose the concentration of activity in the organs of the animals were established by measurements of specimens in the bore-hole counter and scintigrams were made by means of a small animal scanner. The result was an unequivocal temporary dependence of the enrichment of the substance in the organs. The greatest enrichment was found 10 minutes after injection in the liver, then followed blood, kidneys, adrenal glands, seminal vesicles, prostate, abdominal wall and the fatty tissue surrounding the prostate. The blood activity relatively decreased. 7 days after injection an unambiguously higher activity was to be proved in the liver, kidney, adrenal gland than in the blood, whereas the enrichment of iodine-labelled diethylstilbestraldiphosphate in prostate, seminal vesicle, fatty and muscular tissue was always below the enrichment of the blood. But in every case the relation of organ activity to blood activity changed in favour of the organ activity, also with regard to the prostate. 10 minutes after injection the concentration of the activity of the seminal vesicle was somewhat higher than that one of the prostate, but in the further course it was below the concentration of the activity of the prostate. During the first two hours the fatty tissue surrounding the prostate showed a clearly and after the third day a slightly lower activity concentration than the prostate. On the basis of this distribution of the activity for the scintigraphy of the prostate above all a temporary interval of about 10 minutes to 3 hours after the injection of labelled cytonal is involved. The results cause us to perform investigations in men concerning the pharmacokinetics and the possibility of using radioactively labelled cytonal.", "contents": "[Experimental studies of the distribution of intravenously injected iodine-labeled cytonal (diethylstilbestrol diphosphate)]. After intravenous injection the distribution of iodine-labelled diethylstilbestral-diphosphate (cytonal) was investigated in various organs of the rat. For this purpose the concentration of activity in the organs of the animals were established by measurements of specimens in the bore-hole counter and scintigrams were made by means of a small animal scanner. The result was an unequivocal temporary dependence of the enrichment of the substance in the organs. The greatest enrichment was found 10 minutes after injection in the liver, then followed blood, kidneys, adrenal glands, seminal vesicles, prostate, abdominal wall and the fatty tissue surrounding the prostate. The blood activity relatively decreased. 7 days after injection an unambiguously higher activity was to be proved in the liver, kidney, adrenal gland than in the blood, whereas the enrichment of iodine-labelled diethylstilbestraldiphosphate in prostate, seminal vesicle, fatty and muscular tissue was always below the enrichment of the blood. But in every case the relation of organ activity to blood activity changed in favour of the organ activity, also with regard to the prostate. 10 minutes after injection the concentration of the activity of the seminal vesicle was somewhat higher than that one of the prostate, but in the further course it was below the concentration of the activity of the prostate. During the first two hours the fatty tissue surrounding the prostate showed a clearly and after the third day a slightly lower activity concentration than the prostate. On the basis of this distribution of the activity for the scintigraphy of the prostate above all a temporary interval of about 10 minutes to 3 hours after the injection of labelled cytonal is involved. The results cause us to perform investigations in men concerning the pharmacokinetics and the possibility of using radioactively labelled cytonal."} {"id": "PMID:153076", "title": "[Several epidemiologic features of the spread of chickenpox and herpes zoster].", "content": "Epidemiological and statistical data of herpes zoster and chickenpox by such indices as morbidity level, periodicity and month-by-month changes in the incidence of these diseases were compared. The study included 2345 herpes zoster and 11116 chickenpox cases in the course of 5 years (1972--1976). In comparison with herpes zoster, the intensity of chickenpox spread among the population was on the average 4.7 times greater. Of the total number of chickenpox cases the percentage of herpes zoster contituted 21.0. Chickenpox morbidity had marked seasonal cyclic nature with the amplitude of seasonal variations of about 8; as to herpes zoster--there was no annual or seasonal cyclicity. Thus, in the development of chickenpox and herpes zoster epidemic process there was revealed a peculiar tendency inherent to each of these infections; no common epidemiological and statistical regularities in the spread intensity, annual periodicity and seasonal cyclicity were detected.", "contents": "[Several epidemiologic features of the spread of chickenpox and herpes zoster]. Epidemiological and statistical data of herpes zoster and chickenpox by such indices as morbidity level, periodicity and month-by-month changes in the incidence of these diseases were compared. The study included 2345 herpes zoster and 11116 chickenpox cases in the course of 5 years (1972--1976). In comparison with herpes zoster, the intensity of chickenpox spread among the population was on the average 4.7 times greater. Of the total number of chickenpox cases the percentage of herpes zoster contituted 21.0. Chickenpox morbidity had marked seasonal cyclic nature with the amplitude of seasonal variations of about 8; as to herpes zoster--there was no annual or seasonal cyclicity. Thus, in the development of chickenpox and herpes zoster epidemic process there was revealed a peculiar tendency inherent to each of these infections; no common epidemiological and statistical regularities in the spread intensity, annual periodicity and seasonal cyclicity were detected."} {"id": "PMID:153077", "title": "[Several principles for epidemiologic evaluation of individual regions of the Trans-Caucasian plains-piedmont natural focus of plague].", "content": "The authors analyse many-year data concerning the epizootological study of seven landscape-geographical regions of the Eastern Transcaucasus differing by natural conditions and the enzootic intensity. Quantitative assessment of natural nidality determined by the level (norm) of many-year indices calculated for the years of 1955--1974 are presented for each region. Flea vectors were more numerous in localities of stable enzootic manifestation; also the numbers of Meriones erythrourus (carrier rodent) was more stable than in the regions of temporary occurrence of the causative agent and those free of plague. Many-year level of the flea (X. conformis) abundance index equal to one served as the threshold value determining the territory enzooticity.", "contents": "[Several principles for epidemiologic evaluation of individual regions of the Trans-Caucasian plains-piedmont natural focus of plague]. The authors analyse many-year data concerning the epizootological study of seven landscape-geographical regions of the Eastern Transcaucasus differing by natural conditions and the enzootic intensity. Quantitative assessment of natural nidality determined by the level (norm) of many-year indices calculated for the years of 1955--1974 are presented for each region. Flea vectors were more numerous in localities of stable enzootic manifestation; also the numbers of Meriones erythrourus (carrier rodent) was more stable than in the regions of temporary occurrence of the causative agent and those free of plague. Many-year level of the flea (X. conformis) abundance index equal to one served as the threshold value determining the territory enzooticity."} {"id": "PMID:153079", "title": "Submitochondrial localization and function of alkaline inorganic pyrophosphatase in maize seedlings.", "content": "Alkaline inorganic pyrophosphatase and Mg-ATPase are localized within the mitoplast of maize seeding mitochondria. NaF inhibited the PPase activity, whereas oligomycin and dicyclohexylcarbodiimide inhibited the Mg-ATPase activity. The mitoplast preparation synthesized PPi from Pi under conditions excluding hydrolysis of endogenous ATP. PPi synthesis was inhibited by ADP, antimycin A, NaCN and 2,4- dinitrophenol but not by oligomycin. It is suggested that PPi synthesis in the maize seedling mitochondria proceeds at the expense of the energy of electron transport chain and is independent of the ATP synthesis.", "contents": "Submitochondrial localization and function of alkaline inorganic pyrophosphatase in maize seedlings. Alkaline inorganic pyrophosphatase and Mg-ATPase are localized within the mitoplast of maize seeding mitochondria. NaF inhibited the PPase activity, whereas oligomycin and dicyclohexylcarbodiimide inhibited the Mg-ATPase activity. The mitoplast preparation synthesized PPi from Pi under conditions excluding hydrolysis of endogenous ATP. PPi synthesis was inhibited by ADP, antimycin A, NaCN and 2,4- dinitrophenol but not by oligomycin. It is suggested that PPi synthesis in the maize seedling mitochondria proceeds at the expense of the energy of electron transport chain and is independent of the ATP synthesis."} {"id": "PMID:153080", "title": "A study on the effect of dehydroepiandrosterone sulfate on so-called cervical ripening.", "content": "Dehydroepiandrosterone sulfate (DHAS) is now used for a dynamic test of placental function by many obstetricians. While practicing this test, the authors found that DHAS markedly promoted so-called \"cervical ripening\". To study this problem, DHAS of 50 or 100 mg in multiple doses were injected into 132 Japanese pregnant women in their 38th--42nd week of gestation. The change in Bishop score was carefully recorded. Bishop score in the injected groups of primiparae (100 mg) began to rise much sooner than the control groups (p less than 0.01 on seventh day and 14th day). However, such significant difference in the rise of Bishop score was not noted in the multiparae and primiparae with 50 mg. Although the rise of score is not significant, the duration (day) from injection to delivery was shorter in the injected group than the control group (t=2.1529, p less than 0.05 in primiparae with 50 mg, t=3.8829, p less than 0.01 with 100 mg, t=2.1029, p less than 0.05 in multiparae with 50 mg). In some of these cases, labor began or delivery was finished within 24 hrs. Among the factors of Bishop score, mainly the effacement, consistency and dilatation of the cervix were remarkably improved by DHAS injection (p less than 0.01 and less than 0.05). Side effects of any type were not seen in the mothers and foetuses. As a conclusion, DHAS injection in considered to produce favorable conditions for delivery in women with \"unripe cervix\" by softening the soft birth canal. Furthermore, it is suggested that DHAS might play an important role in triggering labor.", "contents": "A study on the effect of dehydroepiandrosterone sulfate on so-called cervical ripening. Dehydroepiandrosterone sulfate (DHAS) is now used for a dynamic test of placental function by many obstetricians. While practicing this test, the authors found that DHAS markedly promoted so-called \"cervical ripening\". To study this problem, DHAS of 50 or 100 mg in multiple doses were injected into 132 Japanese pregnant women in their 38th--42nd week of gestation. The change in Bishop score was carefully recorded. Bishop score in the injected groups of primiparae (100 mg) began to rise much sooner than the control groups (p less than 0.01 on seventh day and 14th day). However, such significant difference in the rise of Bishop score was not noted in the multiparae and primiparae with 50 mg. Although the rise of score is not significant, the duration (day) from injection to delivery was shorter in the injected group than the control group (t=2.1529, p less than 0.05 in primiparae with 50 mg, t=3.8829, p less than 0.01 with 100 mg, t=2.1029, p less than 0.05 in multiparae with 50 mg). In some of these cases, labor began or delivery was finished within 24 hrs. Among the factors of Bishop score, mainly the effacement, consistency and dilatation of the cervix were remarkably improved by DHAS injection (p less than 0.01 and less than 0.05). Side effects of any type were not seen in the mothers and foetuses. As a conclusion, DHAS injection in considered to produce favorable conditions for delivery in women with \"unripe cervix\" by softening the soft birth canal. Furthermore, it is suggested that DHAS might play an important role in triggering labor."} {"id": "PMID:153081", "title": "Assessment of lung function on healthy children using an electronic spirometer and an air-flowmeter before and after inhalation of an adrenergic receptor stimulant.", "content": "VC measured with a Monaghan electronic spirometer equipped with a backflow valve is significantly lower (about 4%) than when measured with the same spirometer without such a valve. The measurements of FEV1.0 were not influenced by the valve. 73 healthy children were investigated with the Monaghan spirometer equipped with the backflow valve and normal reference data were established. The results were very similar to those obtained in an investigation of healthy children with the same spirometer about one year earlier. Reference data on children for a simple flow meter, Airflometer (Glaxo Ltd.), are given. The data correlated very highly to the FEV1.0 values obtained by the Monaghan spirometer. After inhalation of salbutamol healthy children had a small and significant increase of FEV1.0 and of the Airflometer value but not of VC. The deviations of the differences were small. A 6% increase of VC and 10% increase of FEV1.0 were taken as normal upper limits after inhalation of salbutamol. Corresponding increase of the Airflometer values was 15 arbitrary units for children with body heights 116--145 cm and 21 units for children with body heights 146--175 cm.", "contents": "Assessment of lung function on healthy children using an electronic spirometer and an air-flowmeter before and after inhalation of an adrenergic receptor stimulant. VC measured with a Monaghan electronic spirometer equipped with a backflow valve is significantly lower (about 4%) than when measured with the same spirometer without such a valve. The measurements of FEV1.0 were not influenced by the valve. 73 healthy children were investigated with the Monaghan spirometer equipped with the backflow valve and normal reference data were established. The results were very similar to those obtained in an investigation of healthy children with the same spirometer about one year earlier. Reference data on children for a simple flow meter, Airflometer (Glaxo Ltd.), are given. The data correlated very highly to the FEV1.0 values obtained by the Monaghan spirometer. After inhalation of salbutamol healthy children had a small and significant increase of FEV1.0 and of the Airflometer value but not of VC. The deviations of the differences were small. A 6% increase of VC and 10% increase of FEV1.0 were taken as normal upper limits after inhalation of salbutamol. Corresponding increase of the Airflometer values was 15 arbitrary units for children with body heights 116--145 cm and 21 units for children with body heights 146--175 cm."} {"id": "PMID:153083", "title": "The interaction between manganese and ethanol in rats.", "content": "The effects of manganese and ethanol interaction on some chemical constituents of the liver and serum of rats were investigated in order to assess the influence of these substances in inducing susceptibility to manganese poisoning. Manganese and ethanol alone or in combination were administered to the rats as drinking solutions for a period of 30 days. Both the chemicals had a synergistic effect in altering the activity of SDH and ATPase in the liver of rats. The combined treatment also produced significant increase in the activity of adenosine deaminase and alpha-amylase in the liver and serum respectively. Furthermore, the accumulation of manganese in the liver and the increase in the calcium content of the serum were significantly greater after combined ethanol and manganese administration--than either of them alone. These alterations indicate that the toxic effects of manganese are enhanced when the metal and ethanol interact in the biological system.", "contents": "The interaction between manganese and ethanol in rats. The effects of manganese and ethanol interaction on some chemical constituents of the liver and serum of rats were investigated in order to assess the influence of these substances in inducing susceptibility to manganese poisoning. Manganese and ethanol alone or in combination were administered to the rats as drinking solutions for a period of 30 days. Both the chemicals had a synergistic effect in altering the activity of SDH and ATPase in the liver of rats. The combined treatment also produced significant increase in the activity of adenosine deaminase and alpha-amylase in the liver and serum respectively. Furthermore, the accumulation of manganese in the liver and the increase in the calcium content of the serum were significantly greater after combined ethanol and manganese administration--than either of them alone. These alterations indicate that the toxic effects of manganese are enhanced when the metal and ethanol interact in the biological system."} {"id": "PMID:153084", "title": "Intra-abdominal pressure changes during natural movements in man.", "content": "The weight of the upper part of the trunk is partially transmitted to the pelvis via the vertebral column. If the muscle walls around the abdominal cavity are contracted, a high pressure can be generated within the cavity (greater than 200 mmHg). The abdominal space can them transmit part of weight to, e.g., the upper part of the body, Intra-abdominal pressure recordings have been performed during locomotion and other natural movements with intragastric pressure recordings. With each step, there is a phasic variation in pressure, with its peak coinciding with that of the peak vertical force exerted by the leg against the ground. The peak values increase progressively with the speed of walking/running up to a mean of 38 mmHg and with trough values of 16 mmHg. The phasic variations with each step is due to a phasic activation of the abdominal muscles, with an EMG activity starting 50 ms or more before foot contact. If an extra load is put on the back, the posture changes and at the highest speed of running the pressure values are significantly higher than without this additional load. After a jump down from a moderate height of 0.4 m, the average increase is 89 mmHg and can often exceed 100 mmHg. These pressure changes are large and will presumably act to unload the spine under the prevailing biomechanical conditions and, in addition, there will no doubt be an effect on the circulatory system.", "contents": "Intra-abdominal pressure changes during natural movements in man. The weight of the upper part of the trunk is partially transmitted to the pelvis via the vertebral column. If the muscle walls around the abdominal cavity are contracted, a high pressure can be generated within the cavity (greater than 200 mmHg). The abdominal space can them transmit part of weight to, e.g., the upper part of the body, Intra-abdominal pressure recordings have been performed during locomotion and other natural movements with intragastric pressure recordings. With each step, there is a phasic variation in pressure, with its peak coinciding with that of the peak vertical force exerted by the leg against the ground. The peak values increase progressively with the speed of walking/running up to a mean of 38 mmHg and with trough values of 16 mmHg. The phasic variations with each step is due to a phasic activation of the abdominal muscles, with an EMG activity starting 50 ms or more before foot contact. If an extra load is put on the back, the posture changes and at the highest speed of running the pressure values are significantly higher than without this additional load. After a jump down from a moderate height of 0.4 m, the average increase is 89 mmHg and can often exceed 100 mmHg. These pressure changes are large and will presumably act to unload the spine under the prevailing biomechanical conditions and, in addition, there will no doubt be an effect on the circulatory system."} {"id": "PMID:153085", "title": "Metabolic and cardiovascular responses to prolonged noradrenaline load and their antagonism by beta blockade in the rat.", "content": "Rats were given daily injections of noradrenaline (0.5 mg/kg), alprenolol (20 mg/kg), or both together for 17 to 39 days. Noradrenaline injections increased the size of the heart, interscapular brown adipose tissue (ISBAT) and, when the injections were given at a thermoneutral environment, the metabolic activity of the ISBAT. Alprenolol injections tended to reduce the size of the heart and ISBAT and, at a thermoneutral environment, metabolic activity of the skeletal muscle. Furthermore, noradrenaline treatment improved tolerance against body cooling in water at 25 degrees C and enhanced calorigenic response to injected noradrenaline. The metabolic alterations in the rats injected with both drugs together resembled more those of the animals injected with alprenolol only than those of the noradrenaline treated rats. It can be thus concluded that alprenolol, when given together with noradrenaline, antagonized noradrenaline-induced metabolic alterations in the organism. However, the increased pressor response to infused noradrenaline, which was evident in the alprenolol treated animals, was not seen in the animals treated with both drugs. By contrast, these animals, like also the noradrenaline-treated animals, showed decreased pressor response to noradrenaline. This finding suggests that prolonged beta blockade does not abolish the decreased sensitivity of alpha-adrenoreceptors following prolonged noradrenaline load. On the other hand, the hypotonic response to a beta adrenergic drug, isoprenaline, was reduced by prolonged beta blockade despite simultaneous noradrenaline injections.", "contents": "Metabolic and cardiovascular responses to prolonged noradrenaline load and their antagonism by beta blockade in the rat. Rats were given daily injections of noradrenaline (0.5 mg/kg), alprenolol (20 mg/kg), or both together for 17 to 39 days. Noradrenaline injections increased the size of the heart, interscapular brown adipose tissue (ISBAT) and, when the injections were given at a thermoneutral environment, the metabolic activity of the ISBAT. Alprenolol injections tended to reduce the size of the heart and ISBAT and, at a thermoneutral environment, metabolic activity of the skeletal muscle. Furthermore, noradrenaline treatment improved tolerance against body cooling in water at 25 degrees C and enhanced calorigenic response to injected noradrenaline. The metabolic alterations in the rats injected with both drugs together resembled more those of the animals injected with alprenolol only than those of the noradrenaline treated rats. It can be thus concluded that alprenolol, when given together with noradrenaline, antagonized noradrenaline-induced metabolic alterations in the organism. However, the increased pressor response to infused noradrenaline, which was evident in the alprenolol treated animals, was not seen in the animals treated with both drugs. By contrast, these animals, like also the noradrenaline-treated animals, showed decreased pressor response to noradrenaline. This finding suggests that prolonged beta blockade does not abolish the decreased sensitivity of alpha-adrenoreceptors following prolonged noradrenaline load. On the other hand, the hypotonic response to a beta adrenergic drug, isoprenaline, was reduced by prolonged beta blockade despite simultaneous noradrenaline injections."} {"id": "PMID:153087", "title": "Respiratory syncytial virus. I. Concentration and purification of the infectious virus.", "content": "Respiratory syncytial (RS) virus can be purified without losing its infectivity provided that each step of purification is carried out using NT buffer containing over 20% sucrose. Firstly, the virus grown on HES cells is efficiently removed from the culture fluid by precipitating with polyethylene glycol (PEG) 6,000, and the precipitate is suspended in a small amount of 20% sucrose-NT buffer, which results in about a 24-fold concentration of the original material. Then this suspension is centrifugated through 30% sucrose-NT buffer to obtain pellets, which are again suspended in 20% sucrose-NT buffer. This suspension is further centrifuged by discontinuous and linear sucrose density gradient. Finally, the specific infectivity of the purified virus was increased about 3,000-fold over that of the original material.", "contents": "Respiratory syncytial virus. I. Concentration and purification of the infectious virus. Respiratory syncytial (RS) virus can be purified without losing its infectivity provided that each step of purification is carried out using NT buffer containing over 20% sucrose. Firstly, the virus grown on HES cells is efficiently removed from the culture fluid by precipitating with polyethylene glycol (PEG) 6,000, and the precipitate is suspended in a small amount of 20% sucrose-NT buffer, which results in about a 24-fold concentration of the original material. Then this suspension is centrifugated through 30% sucrose-NT buffer to obtain pellets, which are again suspended in 20% sucrose-NT buffer. This suspension is further centrifuged by discontinuous and linear sucrose density gradient. Finally, the specific infectivity of the purified virus was increased about 3,000-fold over that of the original material."} {"id": "PMID:153088", "title": "Studies of liver phosphorylase in hepatic injuries. I. Alteration in enzyme activity.", "content": "Phosphorylase activities (total and a form) were determined in the livers of experimental hepatic injuries with carbon tetrachloride or galactosamine and the livers of patients with liver diseases. Experimental liver injuries caused a slight decrease in total activity in later stages and a marked increase in a form activity in earlier stages. In human livers, low values of total activity were found in acute hepatitis and cirrhosis of the liver with no consistent alteration in a activity. Phosphorylase activities in hepatocellular carcinomas were also low. The importance of the altered phosphorylase activities in hepatic injuries is discussed in relation to the disorder in glycogen metabolism in the injured liver.", "contents": "Studies of liver phosphorylase in hepatic injuries. I. Alteration in enzyme activity. Phosphorylase activities (total and a form) were determined in the livers of experimental hepatic injuries with carbon tetrachloride or galactosamine and the livers of patients with liver diseases. Experimental liver injuries caused a slight decrease in total activity in later stages and a marked increase in a form activity in earlier stages. In human livers, low values of total activity were found in acute hepatitis and cirrhosis of the liver with no consistent alteration in a activity. Phosphorylase activities in hepatocellular carcinomas were also low. The importance of the altered phosphorylase activities in hepatic injuries is discussed in relation to the disorder in glycogen metabolism in the injured liver."} {"id": "PMID:153089", "title": "Induction of hemopoiesis in rat embryonic bone transplanted into adult subcutaneous connective tissue.", "content": "Five pairs of immature, non-hemopoietic femur and tibia from 17-day-old gestating female rat fetuses, whose sex was determined by chromosomal analysis of liver cells, were transplanted into subcutaneous tissues of adult male rats. The original bones were about 3 mm in length and they grew to about 17 mm length at 4 wereks after transplantation. Bone deformation was not evident after transplantation and bone marrow hemopoiesis developed. Bone marrow cytohistologic observations were made on smears, and chromosome analyses were performed on bone marrow cells. Active erythro-, myelo- and megakaryopoiesis were conducted by cells of recipient adult rats. Sex chromosome analysis of cartilage cells from the epiphyses of transplanted bones demonstrated that the growing bones were composed of cells from the grafted embryo. The results thus strongly suggest that the transition of hemopoiesis from liver to bone marrow in late embryonic development is conducted by stem cells migrating through circulating blood and settling in the bone marrow and not by in situ cells differentiating in the bone marrow stroma.", "contents": "Induction of hemopoiesis in rat embryonic bone transplanted into adult subcutaneous connective tissue. Five pairs of immature, non-hemopoietic femur and tibia from 17-day-old gestating female rat fetuses, whose sex was determined by chromosomal analysis of liver cells, were transplanted into subcutaneous tissues of adult male rats. The original bones were about 3 mm in length and they grew to about 17 mm length at 4 wereks after transplantation. Bone deformation was not evident after transplantation and bone marrow hemopoiesis developed. Bone marrow cytohistologic observations were made on smears, and chromosome analyses were performed on bone marrow cells. Active erythro-, myelo- and megakaryopoiesis were conducted by cells of recipient adult rats. Sex chromosome analysis of cartilage cells from the epiphyses of transplanted bones demonstrated that the growing bones were composed of cells from the grafted embryo. The results thus strongly suggest that the transition of hemopoiesis from liver to bone marrow in late embryonic development is conducted by stem cells migrating through circulating blood and settling in the bone marrow and not by in situ cells differentiating in the bone marrow stroma."} {"id": "PMID:153090", "title": "Homovanillic acid in human cerebrospinal fluid.--Its concentration gradient and reduced levels in patients with epilepsy.", "content": "The homovanillic acid (HVA) concentrations in the lumbar cerebrospinal fluid (CSF) were determined in 38 epileptic and 39 control patients. The mean concentration of HVA was 23.9 ng/ml +/- 2.8 SEM for the epileptic group and 30.2 ng/ml +/- 2.1 SEM for the control group, respectively. Thus, HVA was significandly reduced in the patients with epilepsy compared with the controls. The mean HVA in the female patients was higher than in the male patients in both groups but this failed to reach statistical significance. There was no apparent relationship between the degree of reduced HVA concentration and other clinical indexes of the epilepsy (age, type and frequency of seizures, and anticonvulsant medication). For the determination of concentration gradient of HVA three fractions of the spinal CSF were obtained from 11 patients. A pronounced gradient of HVA concentration was found with a ratio of 1 : 1.46 : 1.97 for the first, second and third fractions. This suggests that a standardized conditions for collecting CSF should be employed to study HVA levels in humans.", "contents": "Homovanillic acid in human cerebrospinal fluid.--Its concentration gradient and reduced levels in patients with epilepsy. The homovanillic acid (HVA) concentrations in the lumbar cerebrospinal fluid (CSF) were determined in 38 epileptic and 39 control patients. The mean concentration of HVA was 23.9 ng/ml +/- 2.8 SEM for the epileptic group and 30.2 ng/ml +/- 2.1 SEM for the control group, respectively. Thus, HVA was significandly reduced in the patients with epilepsy compared with the controls. The mean HVA in the female patients was higher than in the male patients in both groups but this failed to reach statistical significance. There was no apparent relationship between the degree of reduced HVA concentration and other clinical indexes of the epilepsy (age, type and frequency of seizures, and anticonvulsant medication). For the determination of concentration gradient of HVA three fractions of the spinal CSF were obtained from 11 patients. A pronounced gradient of HVA concentration was found with a ratio of 1 : 1.46 : 1.97 for the first, second and third fractions. This suggests that a standardized conditions for collecting CSF should be employed to study HVA levels in humans."} {"id": "PMID:153091", "title": "Potential endocrine effects of hypothalamic peptide \"neurotensin\" on pancreas in dogs.", "content": "Effects of synthetic neurotensin on the endocrine pancreas were studied in nine normal and six hypophysectomized (10th to 14th day post-hypophysectomy) dogs. Synthetic neurotensin was administered into the superior pancreaticoduodenal artery, and plasma insulin and glucagon concentrations were measured radioimmunologically. In normal dogs, ten microgram/kg neurotensin administration brought about a mild hyperglycemic response and sharp and rapid increase of plasma insulin and glucagon concentrations in the superior pancreaticoduodenal vein. A biphasic insulin response was noted in the pancreatic vein. The results suggest that a large dose of neurotensin acts directly on the endocrine pancreas causing secretion of these hormones. In hypophysectomized dogs, basal levels of plasma insulin and glucagon were decreased and neurotensin had little effect on the endocrine pancreas even with the administration of a large dose.", "contents": "Potential endocrine effects of hypothalamic peptide \"neurotensin\" on pancreas in dogs. Effects of synthetic neurotensin on the endocrine pancreas were studied in nine normal and six hypophysectomized (10th to 14th day post-hypophysectomy) dogs. Synthetic neurotensin was administered into the superior pancreaticoduodenal artery, and plasma insulin and glucagon concentrations were measured radioimmunologically. In normal dogs, ten microgram/kg neurotensin administration brought about a mild hyperglycemic response and sharp and rapid increase of plasma insulin and glucagon concentrations in the superior pancreaticoduodenal vein. A biphasic insulin response was noted in the pancreatic vein. The results suggest that a large dose of neurotensin acts directly on the endocrine pancreas causing secretion of these hormones. In hypophysectomized dogs, basal levels of plasma insulin and glucagon were decreased and neurotensin had little effect on the endocrine pancreas even with the administration of a large dose."} {"id": "PMID:153092", "title": "Lipoatrophic diabetes. Report of a case.", "content": "The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.", "contents": "Lipoatrophic diabetes. Report of a case. The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily."} {"id": "PMID:153093", "title": "Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern.", "content": "Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.", "contents": "Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern. Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders."} {"id": "PMID:153094", "title": "Studies on human liver bilirubin-UDP-glycosyl transferase. I. Assay methods for bilirubin-UDP-glucuronyl and -xylosyl transferases of human liver specimen.", "content": "Micromethods for estimation of bilirubin uridine diphosphate-glucuronyl and -xylosyl transferases in liver are described. With these methods, a liver specimen as small as 10 mg is sufficient for assay of either enzyme activity and 15 mg is sufficient for assay of both enzymes. Normal values for livers with minimal elevation of SGOT and minimal histological change were 0.260-0.400 U/g protein for glucuronyl transferase and 0.142-0.302 U/g protein for xylosyl transferase.", "contents": "Studies on human liver bilirubin-UDP-glycosyl transferase. I. Assay methods for bilirubin-UDP-glucuronyl and -xylosyl transferases of human liver specimen. Micromethods for estimation of bilirubin uridine diphosphate-glucuronyl and -xylosyl transferases in liver are described. With these methods, a liver specimen as small as 10 mg is sufficient for assay of either enzyme activity and 15 mg is sufficient for assay of both enzymes. Normal values for livers with minimal elevation of SGOT and minimal histological change were 0.260-0.400 U/g protein for glucuronyl transferase and 0.142-0.302 U/g protein for xylosyl transferase."} {"id": "PMID:153095", "title": "An inhibitory substance of glyceraldehyde 3-phosphate dehydrogenase in urine of diabetic patients.", "content": "In urine of diabetics, a significantly great inhibitory activity of glyceraldehyde 3-phosphate dehydrogenase (GAP-Dehyd) was observed compared with that of normal subjects. The 0.2 ml of urine from 41 patients with diabetes mellitus inhibited 0.5 units of GAP-Dehyd by 27.2 +/- 3.0% (mean +/- S.E.M.), while that from 17 normal volunteers inhibited only by 9.0 +/- 1.0% (P less than 0.05). This inhibitory substance was extracted by 90% ethanol from diabetic urine and partially purified by anion exchange chromatography using Dowex-1 (HCOO type). The molecular weight of this substance was confirmed to be 100--300 daltons by an analysis on Biogel P-4 gel filtration chromatography. And analysis by thin layer chromatography using silicagel plate showed that this inhibitor was a ninhydrin reactive substance which has not been reported previously. From the above facts, it was assumed that the inhibitory substance of GAP-Dehyd in urine of diabetics was a new acidic compound of low molecular weight containing an amino residue in the molecule.", "contents": "An inhibitory substance of glyceraldehyde 3-phosphate dehydrogenase in urine of diabetic patients. In urine of diabetics, a significantly great inhibitory activity of glyceraldehyde 3-phosphate dehydrogenase (GAP-Dehyd) was observed compared with that of normal subjects. The 0.2 ml of urine from 41 patients with diabetes mellitus inhibited 0.5 units of GAP-Dehyd by 27.2 +/- 3.0% (mean +/- S.E.M.), while that from 17 normal volunteers inhibited only by 9.0 +/- 1.0% (P less than 0.05). This inhibitory substance was extracted by 90% ethanol from diabetic urine and partially purified by anion exchange chromatography using Dowex-1 (HCOO type). The molecular weight of this substance was confirmed to be 100--300 daltons by an analysis on Biogel P-4 gel filtration chromatography. And analysis by thin layer chromatography using silicagel plate showed that this inhibitor was a ninhydrin reactive substance which has not been reported previously. From the above facts, it was assumed that the inhibitory substance of GAP-Dehyd in urine of diabetics was a new acidic compound of low molecular weight containing an amino residue in the molecule."} {"id": "PMID:153096", "title": "Discriminant analysis of bronchial asthma by linear discriminant function with parameters of flow-volumes: discriminant analysis of bronchial asthma in young male non-smokers.", "content": "With the parameters of a flow-volume and a volume-time curve, the discriminant analysis of bronchial asthma is described. The subjects were classified into three groups (healthy adults, mild asthmatic patients and moderates ones). The difference of the mean vectors of the parameters of the three groups was made clear by the selection methods of the discriminant analysis between any two of the groups both with 6 parameters (%FVC, FEV1.0%, peak flow rate (PF), flow rate at 50% of FVC (V50), flow rate at 25% of FVC (V25), and V50/V25) and with 8 (6 parameters mentioned above and V75, V10). Forced expiratory volume in 1 second percent (FEV1.0%) or V50 was selected at the first step with 6 parameters, and V75 was selected at the first step with 8 parameters. Probabilities of misclassification with 8 parameters were lower than those with 6 ones and the probability of misclassification at the discriminant analysis between healthy adults and mild asthmatic patients with 8 parameters was 15.75% at the final step.", "contents": "Discriminant analysis of bronchial asthma by linear discriminant function with parameters of flow-volumes: discriminant analysis of bronchial asthma in young male non-smokers. With the parameters of a flow-volume and a volume-time curve, the discriminant analysis of bronchial asthma is described. The subjects were classified into three groups (healthy adults, mild asthmatic patients and moderates ones). The difference of the mean vectors of the parameters of the three groups was made clear by the selection methods of the discriminant analysis between any two of the groups both with 6 parameters (%FVC, FEV1.0%, peak flow rate (PF), flow rate at 50% of FVC (V50), flow rate at 25% of FVC (V25), and V50/V25) and with 8 (6 parameters mentioned above and V75, V10). Forced expiratory volume in 1 second percent (FEV1.0%) or V50 was selected at the first step with 6 parameters, and V75 was selected at the first step with 8 parameters. Probabilities of misclassification with 8 parameters were lower than those with 6 ones and the probability of misclassification at the discriminant analysis between healthy adults and mild asthmatic patients with 8 parameters was 15.75% at the final step."} {"id": "PMID:153097", "title": "Immunotherapy of gastric cancer with levamisole.", "content": "Ninety-nine gastric cancer patients initially received levamisole at a daily dose of 150 mg for three consecutive days before operation. This therapy was repeated fortnightly (3-day administration followed by 11-day withdrawal period) for more than one month as long as possible and the survival rate up to 18 months was compared with thas of control patients. The 18 month survival rate of advanced Stage IV patients was significantly higher in patients receiving levamisole than that of control patients. The effects of levamisole in cases of advanced cancer have been discussed in relation to the literature available.", "contents": "Immunotherapy of gastric cancer with levamisole. Ninety-nine gastric cancer patients initially received levamisole at a daily dose of 150 mg for three consecutive days before operation. This therapy was repeated fortnightly (3-day administration followed by 11-day withdrawal period) for more than one month as long as possible and the survival rate up to 18 months was compared with thas of control patients. The 18 month survival rate of advanced Stage IV patients was significantly higher in patients receiving levamisole than that of control patients. The effects of levamisole in cases of advanced cancer have been discussed in relation to the literature available."} {"id": "PMID:153098", "title": "A patient with repeated syncopal attacks after using isosorbide dinitrate.", "content": "The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor.", "contents": "A patient with repeated syncopal attacks after using isosorbide dinitrate. The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor."} {"id": "PMID:153101", "title": "Influence of hemodialysis on electrocardiographic wave forms.", "content": "Alterations in Frank lead electrocardiograms induced by hemodialysis were investigated in 19 patients with chronic renal failure. The most prominent findings after hemodialysis were marked increases in the magnitudes of the R wave in Leads X,Y, and Z, and of the maximal QRS vectors in the frontal, sagittal, and transverse planes. Echocardiographic and roentgenographic examinations revealed no evidence of pericardial effusion before and after hemodialysis. Although the true origin of these findings remains undetermined, it appears reasonable to speculate that the decreased intracavitary blood volume due to hemodialysis may cause an increase in the QRS voltage by a short-circuiting effect. It should be emphasized that a sudden increase in QRS amplitude after hemodialysis might lead to an erroneous diagnosis of left ventricular hypertrophy. The clinician should be aware of such voltage increases when examining the ECGs of patients who undergo hemodialysis.", "contents": "Influence of hemodialysis on electrocardiographic wave forms. Alterations in Frank lead electrocardiograms induced by hemodialysis were investigated in 19 patients with chronic renal failure. The most prominent findings after hemodialysis were marked increases in the magnitudes of the R wave in Leads X,Y, and Z, and of the maximal QRS vectors in the frontal, sagittal, and transverse planes. Echocardiographic and roentgenographic examinations revealed no evidence of pericardial effusion before and after hemodialysis. Although the true origin of these findings remains undetermined, it appears reasonable to speculate that the decreased intracavitary blood volume due to hemodialysis may cause an increase in the QRS voltage by a short-circuiting effect. It should be emphasized that a sudden increase in QRS amplitude after hemodialysis might lead to an erroneous diagnosis of left ventricular hypertrophy. The clinician should be aware of such voltage increases when examining the ECGs of patients who undergo hemodialysis."} {"id": "PMID:153102", "title": "Echocardiographic diagnosis of pulmonary atresia with intact ventricular septum.", "content": "The echocardiographic features of pulmonary valvar atresia with intact ventricular septum are described. The pulmonary valve fails to open during systole: there is a large pre-systolic 'a' wave dip, but the pulmonary valve membrane then returns to its closed diastolic position where it remains for the remainder of the cardiac cycle. The echocardiogram also provides valuable information about right ventricular size, the tricuspid valve, and aorta-mitral and aorta-septal relations.", "contents": "Echocardiographic diagnosis of pulmonary atresia with intact ventricular septum. The echocardiographic features of pulmonary valvar atresia with intact ventricular septum are described. The pulmonary valve fails to open during systole: there is a large pre-systolic 'a' wave dip, but the pulmonary valve membrane then returns to its closed diastolic position where it remains for the remainder of the cardiac cycle. The echocardiogram also provides valuable information about right ventricular size, the tricuspid valve, and aorta-mitral and aorta-septal relations."} {"id": "PMID:153104", "title": "An interdisciplinary course for optometry students specializing in vision training.", "content": "The practice of primary-care optometry often necessitates interaction with professionals from varied backgrounds. This is especially true in the area of vision training, in which close coordination between professionals in schools, agencies, and clinics is necessary. Too often a communcation problem prevents beneficial interdisciplinary liaison. One way of ensuring that optometrists acquire communication and interaction skills is to provide seminars and courses in schools and colleges of optometry. The program described in this paper has helped optometry students refine their communication and referral skills.", "contents": "An interdisciplinary course for optometry students specializing in vision training. The practice of primary-care optometry often necessitates interaction with professionals from varied backgrounds. This is especially true in the area of vision training, in which close coordination between professionals in schools, agencies, and clinics is necessary. Too often a communcation problem prevents beneficial interdisciplinary liaison. One way of ensuring that optometrists acquire communication and interaction skills is to provide seminars and courses in schools and colleges of optometry. The program described in this paper has helped optometry students refine their communication and referral skills."} {"id": "PMID:153109", "title": "[Use of adhesive histoacryl in corneal perforation in the rabbit. Histological and histochemical examinations (author's transl)].", "content": "Rabbit corneas were centrally trephined and the defect filled with Histoacryl. Tissue reactions were examined histologically and histochemically Healing of cornea wounds was delayed for two weeks, after which excessive granulomat\u00f6sen Narbenbildung. Die Grundsubstanz der Hornhaut weist decrease in acid mucopolysaccarides during the time of examination of 32 days.", "contents": "[Use of adhesive histoacryl in corneal perforation in the rabbit. Histological and histochemical examinations (author's transl)]. Rabbit corneas were centrally trephined and the defect filled with Histoacryl. Tissue reactions were examined histologically and histochemically Healing of cornea wounds was delayed for two weeks, after which excessive granulomat\u00f6sen Narbenbildung. Die Grundsubstanz der Hornhaut weist decrease in acid mucopolysaccarides during the time of examination of 32 days."} {"id": "PMID:153110", "title": "[Vocal dysfunction as a consequence of a paresis of the n. laryngeus cranialis after tracheal intubation (author's transl)].", "content": "A case of a transient unilateral paresis of the N. laryngeus cranialis occuring after uneventful tracheal intubation and anaesthesia for laparoscopy is reported. The possible mechanisms of this paresis are discussed.", "contents": "[Vocal dysfunction as a consequence of a paresis of the n. laryngeus cranialis after tracheal intubation (author's transl)]. A case of a transient unilateral paresis of the N. laryngeus cranialis occuring after uneventful tracheal intubation and anaesthesia for laparoscopy is reported. The possible mechanisms of this paresis are discussed."} {"id": "PMID:153115", "title": "Renal function, insulin secretion, and glucose tolerance in mild streptozotocin diabetes in the dog.", "content": "A mild, stable diabetes mellitus was induced in dogs, using a small (20 mg/kg of body weight) dose of streptozotocin in a standard volume of 200 ml infused in 15 minutes. The stability of the diabetes was evidenced by the results of a standard intravenous glucose-tolerance test, insulin response to the glucose load, and urinary glucose excretion. The results of the urinary clearances for urea, creatinine, and phosphate indicated minimal renal toxicosis and that the toxicosis was localized to the tubules.", "contents": "Renal function, insulin secretion, and glucose tolerance in mild streptozotocin diabetes in the dog. A mild, stable diabetes mellitus was induced in dogs, using a small (20 mg/kg of body weight) dose of streptozotocin in a standard volume of 200 ml infused in 15 minutes. The stability of the diabetes was evidenced by the results of a standard intravenous glucose-tolerance test, insulin response to the glucose load, and urinary glucose excretion. The results of the urinary clearances for urea, creatinine, and phosphate indicated minimal renal toxicosis and that the toxicosis was localized to the tubules."} {"id": "PMID:153116", "title": "[Congenital malabsorption of vitamin B12 (Imerslund's syndrome) in a premature girl with Down's syndrome (author's transl)].", "content": "A baby girl, born prematurely and with Down's syndrome, is hospitalized at the age of 51 days for a megaloblastic anemia. The anemia was caused by a selective malabsorption of vitamin B12 (Imerslund's syndrome), even in presence of intrinsic factor. The pathogenesis of different causes of vitamin B12 deficiency is discussed and the favourable development of this case after four years of treatment is shown.", "contents": "[Congenital malabsorption of vitamin B12 (Imerslund's syndrome) in a premature girl with Down's syndrome (author's transl)]. A baby girl, born prematurely and with Down's syndrome, is hospitalized at the age of 51 days for a megaloblastic anemia. The anemia was caused by a selective malabsorption of vitamin B12 (Imerslund's syndrome), even in presence of intrinsic factor. The pathogenesis of different causes of vitamin B12 deficiency is discussed and the favourable development of this case after four years of treatment is shown."} {"id": "PMID:153117", "title": "Panniculectomy and the difficult ileostomy for urinary diversion.", "content": "This paper describes a helpful operation for revision of the difficult ileal stoma for urinary diversion. By using the standard technique of panniculectomy or abdominal lipectomy, the ileal loop can be left in the same position on the abdominal wall and healthy, viable tissue can be mobilized and repositioned to enable the urological surgeon to perform the cutaneous portion of the procedure again and to refashion the ileal loop. This saves the patient an operation of greater magnitude and risk.", "contents": "Panniculectomy and the difficult ileostomy for urinary diversion. This paper describes a helpful operation for revision of the difficult ileal stoma for urinary diversion. By using the standard technique of panniculectomy or abdominal lipectomy, the ileal loop can be left in the same position on the abdominal wall and healthy, viable tissue can be mobilized and repositioned to enable the urological surgeon to perform the cutaneous portion of the procedure again and to refashion the ileal loop. This saves the patient an operation of greater magnitude and risk."} {"id": "PMID:153118", "title": "Rhinophyma: surgical refinements.", "content": "Rhinophyma is classically a benign tumor of unknown etiology and pathogenesis. Once fully developed, it requires surgical treatment; its management has invited controversy for more than a century. We favor electrosurgical sculpturing, removal of the burned tissue by abrasion, treatment of the entire nasal cover as a unit, and the utilization of biological dressings to promote reepithelization. The cosmetic results have been gratifying.", "contents": "Rhinophyma: surgical refinements. Rhinophyma is classically a benign tumor of unknown etiology and pathogenesis. Once fully developed, it requires surgical treatment; its management has invited controversy for more than a century. We favor electrosurgical sculpturing, removal of the burned tissue by abrasion, treatment of the entire nasal cover as a unit, and the utilization of biological dressings to promote reepithelization. The cosmetic results have been gratifying."} {"id": "PMID:153119", "title": "A linkage study of the loci for Huntington's disease and some common polymorphic markers.", "content": "The phenotypic frequencies of 24 polymorphic blood markers in a sample of patients with Huntington's disease (HD) have been compared with those in a sample of healthy Australian volunteers in an effort to detect any associations between HD and the markers concerned. The Rh factor, c, has a significantly lower frequency in the HD sample while ACP1c and Gm1,2 have a significantly higher frequency. The linkage relations of the HD locus have been analysed with respect to the various marker loci concerned. This analysis involved the development of methods to overcome the general lack of genetic data concerning the affected parent and the possibility that presently unaffected offspring may be asymptomatic carriers of the HD gene. The results suggest that close linkage between the HD locus and Fy, ADA, ACP1, Gc or Bg is highly unlikely. They also suggest a low probability of close linkage to ABO, Rh, Jk, Lu, AK1, PGM1 or C3. Positive linkage scores were obtained for P, Hp and Gm. The results are inconclusive for MNSs, K, Le, Se, GPT and Inv. The available data were uninformative for linkage between the HD locus and Co, 6-PGD or E1.", "contents": "A linkage study of the loci for Huntington's disease and some common polymorphic markers. The phenotypic frequencies of 24 polymorphic blood markers in a sample of patients with Huntington's disease (HD) have been compared with those in a sample of healthy Australian volunteers in an effort to detect any associations between HD and the markers concerned. The Rh factor, c, has a significantly lower frequency in the HD sample while ACP1c and Gm1,2 have a significantly higher frequency. The linkage relations of the HD locus have been analysed with respect to the various marker loci concerned. This analysis involved the development of methods to overcome the general lack of genetic data concerning the affected parent and the possibility that presently unaffected offspring may be asymptomatic carriers of the HD gene. The results suggest that close linkage between the HD locus and Fy, ADA, ACP1, Gc or Bg is highly unlikely. They also suggest a low probability of close linkage to ABO, Rh, Jk, Lu, AK1, PGM1 or C3. Positive linkage scores were obtained for P, Hp and Gm. The results are inconclusive for MNSs, K, Le, Se, GPT and Inv. The available data were uninformative for linkage between the HD locus and Co, 6-PGD or E1."} {"id": "PMID:153120", "title": "Perinatal risk factors in children with serious motor and mental handicaps.", "content": "Fifty children with marked neurological abnormality manifested by moderate or severe motor disability and severe mental retardation were compared with a large control population with respect to prospectively ascertained perinatal characteristics. None of 60 prenatal factors distinguished the affected group from controls. In labor and delivery, lowest fetal heart rate in the second stage of labor, arrested progress of labor, and use of midforceps discriminated between the two groups. Neonatal characteristics of children who were later severely handicapped differed from controls, particularly with respect to difficulty in initiating and maintaining respiration, intracranial hemorrhage, neonatal seizures, low birth weight and small head circumference, lowest hemoglobin or hematocrit, and overall neurological status. Multivariate analysis, including factors from all epochs, indicated that intracranial hemorrhage and neonatal seizures were the strongest independent discriminators between the neurologically impaired children and controls.", "contents": "Perinatal risk factors in children with serious motor and mental handicaps. Fifty children with marked neurological abnormality manifested by moderate or severe motor disability and severe mental retardation were compared with a large control population with respect to prospectively ascertained perinatal characteristics. None of 60 prenatal factors distinguished the affected group from controls. In labor and delivery, lowest fetal heart rate in the second stage of labor, arrested progress of labor, and use of midforceps discriminated between the two groups. Neonatal characteristics of children who were later severely handicapped differed from controls, particularly with respect to difficulty in initiating and maintaining respiration, intracranial hemorrhage, neonatal seizures, low birth weight and small head circumference, lowest hemoglobin or hematocrit, and overall neurological status. Multivariate analysis, including factors from all epochs, indicated that intracranial hemorrhage and neonatal seizures were the strongest independent discriminators between the neurologically impaired children and controls."} {"id": "PMID:153121", "title": "Infantile spasms in Down syndrome: a report of 5 cases and review of the literature.", "content": "Five patients with Down syndrome (DS) and infantile spasms were examined in a four-year interval. Previous reports of this association have been infrequent except during experimental treatment with 5-hydroxytryptophan, a precursor of serotonin. Malformations of the brain in DS are associated with an increased incidence of epilepsy, and both gross and cytoarchitectural anomalies have been described. The severity and distribution of these central nervous system anomalies presumably predispose to the infantile spasms. The contribution of altered serotonin metabolism is uncertain.", "contents": "Infantile spasms in Down syndrome: a report of 5 cases and review of the literature. Five patients with Down syndrome (DS) and infantile spasms were examined in a four-year interval. Previous reports of this association have been infrequent except during experimental treatment with 5-hydroxytryptophan, a precursor of serotonin. Malformations of the brain in DS are associated with an increased incidence of epilepsy, and both gross and cytoarchitectural anomalies have been described. The severity and distribution of these central nervous system anomalies presumably predispose to the infantile spasms. The contribution of altered serotonin metabolism is uncertain."} {"id": "PMID:153122", "title": "Huntington's dementia. Clinical and neuropsychological features.", "content": "The neuropsychiatric syndrome of Huntington's disease is outlined in this report with an emphasis on the cognitive deficits that lend themselves to future neurobehavioral research. Eighteen patients without disabling cognitive or psychiatric symptoms were evaluated for a period of 3 to 15 weeks, with assessment of their cognitive disorder, psychiatric, and neurological symptoms. Neuropsychological examination included repeated mental status examination, the Wechsler Adult Intelligence Scale (WAIS), and, for some, parietal lobe testing. In addition to suffering from a loss of finely detailed memories, patients demonstrated impaired organizing, sequencing, planning, and recalling of information on request. On the WAIS, mean verbal and performance scores were not significantly different. Neuropsychological findings suggested that the Huntington's disease pattern of cognitive impairment is not initially diffuse and homogeneous, but characterized by a relative sparing of several higher cortical functions. Many patients had increased irritability and labile affect. The similarity of Huntington's disease to frontal lobe syndromes is also discussed.", "contents": "Huntington's dementia. Clinical and neuropsychological features. The neuropsychiatric syndrome of Huntington's disease is outlined in this report with an emphasis on the cognitive deficits that lend themselves to future neurobehavioral research. Eighteen patients without disabling cognitive or psychiatric symptoms were evaluated for a period of 3 to 15 weeks, with assessment of their cognitive disorder, psychiatric, and neurological symptoms. Neuropsychological examination included repeated mental status examination, the Wechsler Adult Intelligence Scale (WAIS), and, for some, parietal lobe testing. In addition to suffering from a loss of finely detailed memories, patients demonstrated impaired organizing, sequencing, planning, and recalling of information on request. On the WAIS, mean verbal and performance scores were not significantly different. Neuropsychological findings suggested that the Huntington's disease pattern of cognitive impairment is not initially diffuse and homogeneous, but characterized by a relative sparing of several higher cortical functions. Many patients had increased irritability and labile affect. The similarity of Huntington's disease to frontal lobe syndromes is also discussed."} {"id": "PMID:153123", "title": "Levels of principal 17-ketosteroid fractions in urine of breast cancer patients with or without malignant evolutive push.", "content": "The main fractions of 17-ketosteroids were estimated in 102 women with breast cancer. Sixty two patients were cases with rapid evolution (malignant evolutive push) or very rapid evolution (inflammatory breast carcinoma). The mean ethiocholanolone levels and partially androsterone levels were significantly decreased in patients with rapid evolution in comparison with the corresponding values found in patients with breast cancer of slow growth.", "contents": "Levels of principal 17-ketosteroid fractions in urine of breast cancer patients with or without malignant evolutive push. The main fractions of 17-ketosteroids were estimated in 102 women with breast cancer. Sixty two patients were cases with rapid evolution (malignant evolutive push) or very rapid evolution (inflammatory breast carcinoma). The mean ethiocholanolone levels and partially androsterone levels were significantly decreased in patients with rapid evolution in comparison with the corresponding values found in patients with breast cancer of slow growth."} {"id": "PMID:153124", "title": "Venous malformations of the heart.", "content": "So-called varicosities of the fossa ovalis are rare, venous malformations, which have also been previously labeled angiomas. In four cases encountered as incidental autopsy findings, the microscopic appearance was that of dilated venous channels. Veins larger than 100 micrometer in diameter were found close to the posteroinferior rim of the fossa ovalis in 18 of 21 consecutive, routine autopsy cases. The pathogenesis of the venous dilation is unknown but it may be related to the development of the interatrial septim. The term venous malformation seems preferable to varix for such lesions.", "contents": "Venous malformations of the heart. So-called varicosities of the fossa ovalis are rare, venous malformations, which have also been previously labeled angiomas. In four cases encountered as incidental autopsy findings, the microscopic appearance was that of dilated venous channels. Veins larger than 100 micrometer in diameter were found close to the posteroinferior rim of the fossa ovalis in 18 of 21 consecutive, routine autopsy cases. The pathogenesis of the venous dilation is unknown but it may be related to the development of the interatrial septim. The term venous malformation seems preferable to varix for such lesions."} {"id": "PMID:153125", "title": "[Anterior lumbar disc herniations (author's transl)].", "content": "Anterior lumbar disc herniations can easily and clearly be evidented by discography. The morbidity and, especially, the clinical importance of this entity, however, has been described by some authors only. According to our own experience with discography, ventral lumbar disc herniation seems to be correlated with a painful syndrome consisting of both a typical and circumscribed backache and pain radiating into the abdominal cavity and genital area along the lateral aspect of the lumbar region.", "contents": "[Anterior lumbar disc herniations (author's transl)]. Anterior lumbar disc herniations can easily and clearly be evidented by discography. The morbidity and, especially, the clinical importance of this entity, however, has been described by some authors only. According to our own experience with discography, ventral lumbar disc herniation seems to be correlated with a painful syndrome consisting of both a typical and circumscribed backache and pain radiating into the abdominal cavity and genital area along the lateral aspect of the lumbar region."} {"id": "PMID:153126", "title": "Sexual attitudes, behavior and satisfaction for able-bodied and disabled participants attending workshops in human sexuality.", "content": "Since 1973, Sexual Attitude Reassessment (SAR) Workshops have been conducted for persons with physical handicaps, health care professionals and interested members of the community. Although reassessment of personal sexual attitudes is the primary objective of the workshops, several closely related objectives have emerged: (1) evaluation of the impact of the experience on changing both sexual attitudes and behaviors; (2) evaluation of the sexual satisfaction and problem areas of participants with particular reference to persons with physical disabilities; and (3) provision of an institute-wide catalyst for initiating programs and services based on newly identified unmet needs. This article presents data from 15 workshops with emphasis on comparing the sexual attitudes, behavior and satisfaction of the able-bodied and the disabled participants. Of the 650 participants, 98 (15%) were disabled and of this group approximately 75% had spinal cord injury. Comparison of pre- and post-workshop responses to sexual attitude scales showed similar and significant changes on four of nine scales for both the able-bodied and disabled groups. Analysis of sexual behavior and satisfaction by physical status revealed that the disabled participants were less active than the able-bodied participants although both groups reported similar percentages of satisfaction (38 and 41% respectively) with their current level of sexual activity. Lack of partners was cited most frequently by both groups as the major reason for dissatisfaction with current sexual status. Implications of these findings are discussed with regard to sexual counseling and areas of further research.", "contents": "Sexual attitudes, behavior and satisfaction for able-bodied and disabled participants attending workshops in human sexuality. Since 1973, Sexual Attitude Reassessment (SAR) Workshops have been conducted for persons with physical handicaps, health care professionals and interested members of the community. Although reassessment of personal sexual attitudes is the primary objective of the workshops, several closely related objectives have emerged: (1) evaluation of the impact of the experience on changing both sexual attitudes and behaviors; (2) evaluation of the sexual satisfaction and problem areas of participants with particular reference to persons with physical disabilities; and (3) provision of an institute-wide catalyst for initiating programs and services based on newly identified unmet needs. This article presents data from 15 workshops with emphasis on comparing the sexual attitudes, behavior and satisfaction of the able-bodied and the disabled participants. Of the 650 participants, 98 (15%) were disabled and of this group approximately 75% had spinal cord injury. Comparison of pre- and post-workshop responses to sexual attitude scales showed similar and significant changes on four of nine scales for both the able-bodied and disabled groups. Analysis of sexual behavior and satisfaction by physical status revealed that the disabled participants were less active than the able-bodied participants although both groups reported similar percentages of satisfaction (38 and 41% respectively) with their current level of sexual activity. Lack of partners was cited most frequently by both groups as the major reason for dissatisfaction with current sexual status. Implications of these findings are discussed with regard to sexual counseling and areas of further research."} {"id": "PMID:153127", "title": "Gravitational lumbar traction.", "content": "Low back and extremity pain is often secondary to inflammation of the nerve root or sinuvertebral nerve. Gravitational lumbar reduction therapy may relieve such pain. The results in a series of 121 cases are presented.", "contents": "Gravitational lumbar traction. Low back and extremity pain is often secondary to inflammation of the nerve root or sinuvertebral nerve. Gravitational lumbar reduction therapy may relieve such pain. The results in a series of 121 cases are presented."} {"id": "PMID:153134", "title": "Differentiation of the changes in alkaline phosphatase from calcium ion-activated adenosine triphosphatase activities associated with increased calcium absorption in chick intestine.", "content": "The pattern of response of the intestinal enzymes Ca2+-activated adenosine triphosphatase and alkaline phosphatase in the chick to 1,25-dihydroxycholecalciferol is consistent with a role for the former but not the latter enzyme in the vitamin D-dependent absorption of calcium.", "contents": "Differentiation of the changes in alkaline phosphatase from calcium ion-activated adenosine triphosphatase activities associated with increased calcium absorption in chick intestine. The pattern of response of the intestinal enzymes Ca2+-activated adenosine triphosphatase and alkaline phosphatase in the chick to 1,25-dihydroxycholecalciferol is consistent with a role for the former but not the latter enzyme in the vitamin D-dependent absorption of calcium."} {"id": "PMID:153135", "title": "Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells.", "content": "The phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. The present report examines the affects of these analogues on the metabolism of neuroblastoma cells. p-Chlorophenylalanine inhibited growth and was toxic to neuroblastoma cells. Although in vivo this analogue increased cell monoribosomes by 42%, it did not significantly affect poly(U)-directed protein synthesis in vitro. P-Chlorophenylalanine did not compete with phenylalanine or tyrosine for aminoacylation of tRNA and was therefore not substituted for those amino acids in nascent polypeptides. The initial cellular uptake of various large neutral amino acids was inhibited by this analogue but did not affect the flux of amino acids already in the cell; this suggested that an alteration of the cell's amino acid pools was not responsible for the cytotoxicity of the analogues. In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture. The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed.", "contents": "Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells. The phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. The present report examines the affects of these analogues on the metabolism of neuroblastoma cells. p-Chlorophenylalanine inhibited growth and was toxic to neuroblastoma cells. Although in vivo this analogue increased cell monoribosomes by 42%, it did not significantly affect poly(U)-directed protein synthesis in vitro. P-Chlorophenylalanine did not compete with phenylalanine or tyrosine for aminoacylation of tRNA and was therefore not substituted for those amino acids in nascent polypeptides. The initial cellular uptake of various large neutral amino acids was inhibited by this analogue but did not affect the flux of amino acids already in the cell; this suggested that an alteration of the cell's amino acid pools was not responsible for the cytotoxicity of the analogues. In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture. The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed."} {"id": "PMID:153136", "title": "Properties of the membrane proteins of rat liver lysosomes. The majority of lysosomal membrane proteins are exposed to the cytoplasm.", "content": "Rat liver lysosomes were lysed and subfractionated by differential centrifugation through 0.2M-NaCl to yield a membranous pellet. This membrane fraction contains less than 20% of the lysosomal protein, adenosine triphosphatase activity of about 1.2mumol/min per mg of protein, 120nmol of thiol groups/mg of protein and at least 16 protein and glycoprotein bands on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The gel patterns of membranes isolated from lysosomes after treatment with (1) [125I]iodidehydrogen peroxide-lactoperoxidase, (2) toluene 2,4-di-isocyanate-activated bovine serum albumin, (3) trypsin and (4) subtilisin indicate that most of the membrane proteins are exposed to the cytoplasm. These exposed proteins are candidates for intracellular receptors which recognize either substances that are to be degraded or vesicles containing those substances.", "contents": "Properties of the membrane proteins of rat liver lysosomes. The majority of lysosomal membrane proteins are exposed to the cytoplasm. Rat liver lysosomes were lysed and subfractionated by differential centrifugation through 0.2M-NaCl to yield a membranous pellet. This membrane fraction contains less than 20% of the lysosomal protein, adenosine triphosphatase activity of about 1.2mumol/min per mg of protein, 120nmol of thiol groups/mg of protein and at least 16 protein and glycoprotein bands on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The gel patterns of membranes isolated from lysosomes after treatment with (1) [125I]iodidehydrogen peroxide-lactoperoxidase, (2) toluene 2,4-di-isocyanate-activated bovine serum albumin, (3) trypsin and (4) subtilisin indicate that most of the membrane proteins are exposed to the cytoplasm. These exposed proteins are candidates for intracellular receptors which recognize either substances that are to be degraded or vesicles containing those substances."} {"id": "PMID:153133", "title": "Development and reversal of pressure-induced cardiac hypertrophy. Light and electron microscopic study in the rat under temporary aortic constriction.", "content": "Light and electron microscopy, combined with morphometry, were utilized to study myocardial cell modifications induced by a temporary abdominal aortic constriction in the rat. During the early stage of active hypertrophy, cell enlargement in the subendocardial layers of the left ventricle was predominant. This enlargement may be partly due to intracellular edema, characteristic of cell damage. Degenerative foci leading to fibrous scars were found primarily in the subendocardium and midwall layers. The times taken by the different cell structures to adapt to modifications of the load were rather different; some adapted very rapidly (nucleoli, intercalated discs), while others were much slower (cell diameter, mitochondria).", "contents": "Development and reversal of pressure-induced cardiac hypertrophy. Light and electron microscopic study in the rat under temporary aortic constriction. Light and electron microscopy, combined with morphometry, were utilized to study myocardial cell modifications induced by a temporary abdominal aortic constriction in the rat. During the early stage of active hypertrophy, cell enlargement in the subendocardial layers of the left ventricle was predominant. This enlargement may be partly due to intracellular edema, characteristic of cell damage. Degenerative foci leading to fibrous scars were found primarily in the subendocardium and midwall layers. The times taken by the different cell structures to adapt to modifications of the load were rather different; some adapted very rapidly (nucleoli, intercalated discs), while others were much slower (cell diameter, mitochondria)."} {"id": "PMID:153144", "title": "Survey for immune complexes in disseminated gonococcal arthritis-dermatitis syndrome.", "content": "Seventeen patients with characteristic disseminated gonococcal arthritis-dermatitis syndrome were studied for the presence of immune complexes, and circulating gonococcal antigen and antibody. The two immune complex techniques, monoclonal rheumatoid factor assay and cryoglobulin survey, did not reveal any consistent abnormalities. Complement levels (CH50, C'3, C'4) were not consistent with peripheral consumption except in 2 patients with coinciding systemic lupus erythematosus. Gonococcal antibody was detected in 47% of patients when they presented with the syndrome. However, gonococcal antigen was not found in either serum or synovial fluid. These results do not support the hypothesis that circulating immune complexes are involved in the pathogenesis of disseminated gonococcal arthritis-dermatitis syndrome.", "contents": "Survey for immune complexes in disseminated gonococcal arthritis-dermatitis syndrome. Seventeen patients with characteristic disseminated gonococcal arthritis-dermatitis syndrome were studied for the presence of immune complexes, and circulating gonococcal antigen and antibody. The two immune complex techniques, monoclonal rheumatoid factor assay and cryoglobulin survey, did not reveal any consistent abnormalities. Complement levels (CH50, C'3, C'4) were not consistent with peripheral consumption except in 2 patients with coinciding systemic lupus erythematosus. Gonococcal antibody was detected in 47% of patients when they presented with the syndrome. However, gonococcal antigen was not found in either serum or synovial fluid. These results do not support the hypothesis that circulating immune complexes are involved in the pathogenesis of disseminated gonococcal arthritis-dermatitis syndrome."} {"id": "PMID:153148", "title": "Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange.", "content": "The effect of actin concentration on the myosin catalyzed exchange of phosphate oxygens with water accompanying ATP hydrolysis has been investigated. The extent of exchange was found to extrapolate to zero at infinite actin concentration at 23 and 0 degrees C for myosin subfragments S1(A1) and S1(A2). This result is consistent with actin associating directly with the product of the hydrolysis step and is not readily consistent with refractory state schemes in which the entire flow goes via a dissociating pathway. The possibility of a refractory state in the form of a phosphorylated intermediate or a bound metaphosphate state with hydrolysis occurring in the transition to the refractory state merits consideration. A full analysis of the dependence of intermediate exchange on the rate constants of the acto-S1 scheme is given and the errors arising from other methods of analysis are discussed. The rate of oxygen exchange was measured as 10 s-1 (23 degrees C) a value comparable with but slightly lower than the rate of reversal of the ATP cleavage step.", "contents": "Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange. The effect of actin concentration on the myosin catalyzed exchange of phosphate oxygens with water accompanying ATP hydrolysis has been investigated. The extent of exchange was found to extrapolate to zero at infinite actin concentration at 23 and 0 degrees C for myosin subfragments S1(A1) and S1(A2). This result is consistent with actin associating directly with the product of the hydrolysis step and is not readily consistent with refractory state schemes in which the entire flow goes via a dissociating pathway. The possibility of a refractory state in the form of a phosphorylated intermediate or a bound metaphosphate state with hydrolysis occurring in the transition to the refractory state merits consideration. A full analysis of the dependence of intermediate exchange on the rate constants of the acto-S1 scheme is given and the errors arising from other methods of analysis are discussed. The rate of oxygen exchange was measured as 10 s-1 (23 degrees C) a value comparable with but slightly lower than the rate of reversal of the ATP cleavage step."} {"id": "PMID:153149", "title": "Actin mediated release of ATP from a myosin-ATP complex.", "content": "The apparent second-order rate constant, ka-2, of actin binding to a myosin-ATP state (M*.ATP) and releasing ATP to the medium has been determined by two methods. The first was the measurement of the amount of ATP released when actin was added to the intermediate state, M*.ATP; the second was the measurement of oxygen exchange between ATP and HOH. A quantitative treatment of ATP in equilibrium HOH exchange is given to allow extraction of elementary rate constants from the data. Agreement between the two methods was good and at low ionic strength and 23 degrees C, ka-2 is 6 X 10(5) M-1 s-1 which is about one-third the value of the apparent second-order rate constant, ka4, of actin binding to the myosin product state (M**.ADP.Pi). The determination of ka-2 allows a lower limit of 6 s-1 to be placed upon the first-order rate of ATP release from AM.ATP. This is to be compared with a value of less than or equal to 1.5 X 10(-4) s-1 for the equivalent steps of the myosin scheme; thus actin enhances the rate by a factor of 4 X 10(4) or more. A greater proportion of the bound ATP is released to the medium as ATP with increasing actin concentration. This reflects the contribution to rate limitation at saturating actin concentration of steps between myosin states dissociated from actin.", "contents": "Actin mediated release of ATP from a myosin-ATP complex. The apparent second-order rate constant, ka-2, of actin binding to a myosin-ATP state (M*.ATP) and releasing ATP to the medium has been determined by two methods. The first was the measurement of the amount of ATP released when actin was added to the intermediate state, M*.ATP; the second was the measurement of oxygen exchange between ATP and HOH. A quantitative treatment of ATP in equilibrium HOH exchange is given to allow extraction of elementary rate constants from the data. Agreement between the two methods was good and at low ionic strength and 23 degrees C, ka-2 is 6 X 10(5) M-1 s-1 which is about one-third the value of the apparent second-order rate constant, ka4, of actin binding to the myosin product state (M**.ADP.Pi). The determination of ka-2 allows a lower limit of 6 s-1 to be placed upon the first-order rate of ATP release from AM.ATP. This is to be compared with a value of less than or equal to 1.5 X 10(-4) s-1 for the equivalent steps of the myosin scheme; thus actin enhances the rate by a factor of 4 X 10(4) or more. A greater proportion of the bound ATP is released to the medium as ATP with increasing actin concentration. This reflects the contribution to rate limitation at saturating actin concentration of steps between myosin states dissociated from actin."} {"id": "PMID:153150", "title": "Interaction of myosin subfragments with F-actin.", "content": "The effect of ionic strength, temperature, and divalent cations on the association of myosin with actin was determined in the ultracentrifuge using scanning absorption optics. The association constant (Ka) for the binding of heavy meromyosin (HmM) to F-actin was 1 X 10(7) M-1 at 20 degrees C, in 0.10 M KCl, 0.01 M imidazole (pH 7.0), 5 MM potassium phosphate, 1 mM MgCl2, and 0.3 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Ka was the same for HMM prepared by trypsin or chymotrypsin. The affinity of subfragment 1 (S1) for actin under the same ionic conditions was 3 X 10(6) M-1. Varying the preparative procedure for S1 had little effect on Ka. The small difference in binding energy between HMM and S1 suggests that either only one head can bind strongly to actin at a time or that free energy is lost during the sterically unfavorable attachment of the two heads to actin.", "contents": "Interaction of myosin subfragments with F-actin. The effect of ionic strength, temperature, and divalent cations on the association of myosin with actin was determined in the ultracentrifuge using scanning absorption optics. The association constant (Ka) for the binding of heavy meromyosin (HmM) to F-actin was 1 X 10(7) M-1 at 20 degrees C, in 0.10 M KCl, 0.01 M imidazole (pH 7.0), 5 MM potassium phosphate, 1 mM MgCl2, and 0.3 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Ka was the same for HMM prepared by trypsin or chymotrypsin. The affinity of subfragment 1 (S1) for actin under the same ionic conditions was 3 X 10(6) M-1. Varying the preparative procedure for S1 had little effect on Ka. The small difference in binding energy between HMM and S1 suggests that either only one head can bind strongly to actin at a time or that free energy is lost during the sterically unfavorable attachment of the two heads to actin."} {"id": "PMID:153151", "title": "Galactose-6-sulfatase from Actinobacillus sp. IFO-13310 and its action on sulfated oligosaccharides from keratan sulfate.", "content": "A 6-sulfatase specific for sugasr of the galactose configuration was purified 81-fold from the crude extract of Actinobacillus sp. IFO-13310. This preparation contained activity towards both N-acetylgalactosamine 6-sulfate and galactose 6-sulfate (relative activity, 2.4 : 1). The enzyme also release inorganic sulfate from the non-reducing galactose 6-sulfate end group of a trisaccharide disulfate prepared from keratan sulfate by sequential degradation with endo-beta-galactosidase, N-acetylglucosamine-6-sulfatase and exo-beta-N-acetylglucosaminidase. In addition, a tetrasaccharide trisulfate bearing the non-reducing N-acetylglucosamine 6-sulfate end group, also enzymatically prepared from keratan sulfate, was degraded to give rise to inorganic sulfate, N-acetylglucosamine and galactose by the sequential action of this enzyme, N-acetylglucosamine-6-sulfatase, exo-beta-N-acetylglucosaminidase and exo-beta-galactosidase (Charonia lampas).", "contents": "Galactose-6-sulfatase from Actinobacillus sp. IFO-13310 and its action on sulfated oligosaccharides from keratan sulfate. A 6-sulfatase specific for sugasr of the galactose configuration was purified 81-fold from the crude extract of Actinobacillus sp. IFO-13310. This preparation contained activity towards both N-acetylgalactosamine 6-sulfate and galactose 6-sulfate (relative activity, 2.4 : 1). The enzyme also release inorganic sulfate from the non-reducing galactose 6-sulfate end group of a trisaccharide disulfate prepared from keratan sulfate by sequential degradation with endo-beta-galactosidase, N-acetylglucosamine-6-sulfatase and exo-beta-N-acetylglucosaminidase. In addition, a tetrasaccharide trisulfate bearing the non-reducing N-acetylglucosamine 6-sulfate end group, also enzymatically prepared from keratan sulfate, was degraded to give rise to inorganic sulfate, N-acetylglucosamine and galactose by the sequential action of this enzyme, N-acetylglucosamine-6-sulfatase, exo-beta-N-acetylglucosaminidase and exo-beta-galactosidase (Charonia lampas)."} {"id": "PMID:153152", "title": "Evidence for the non-filamentous aggregation of actin induced by lanthanide ions.", "content": "We varied the molar ratio of added lanthanide ion to skeletal muscle actin (M3+/A) and observed their effects on the change in reduced viscosity (Nred) in the presence of polymerizing quantities of salt (0.1 M KC1). Once the concentration of the lanthanide ion exceeds the concentration of the nucleotide present (0.2 mM ATP), we noted that with M3+/A ratios up to 4: (a) there was a sharp peak in the observed Nred above the level achieved by control F-actin; (b) the magnitude of (a) was shown to be a function of the initial G-actin concentration. With an M3+/A ratio of greater than 4 we observed: (i) a sharp fall in the observed Nred; (ii) the formation of an insoluble aggregate of actin; (iii) the formation of (ii) was completely reversed by removal of the M3+; (iv) a complete inhibition of the ATP hydrolysis which always accompanies the G- to F-actin transition; (v) the number of mol of M3+ required to completely inhibit the rise in Nred (above the viscosity of G-actin) was a function of the ionic radii of the 11 lanthanide ions tested; and (vi) the effects described in (i) were not mimicked when the initial protein was in the F form. In the absence of added KCI, divalent cations (e.g. Mg2+) polymerize G-actin but this effect is not mimicked by the addition of the lanthanide ions. However, under these conditions the lanthanide ions cause the formation of an insoluble aggregate of actin. We conclude that with greater than 4 mol of lanthanide ions, G-actin aggregates in a form which contains little or no F-actin and that the lanthanide ion-induced aggregates are therefore different from the Mg2+-induced F-actin paracrystals.", "contents": "Evidence for the non-filamentous aggregation of actin induced by lanthanide ions. We varied the molar ratio of added lanthanide ion to skeletal muscle actin (M3+/A) and observed their effects on the change in reduced viscosity (Nred) in the presence of polymerizing quantities of salt (0.1 M KC1). Once the concentration of the lanthanide ion exceeds the concentration of the nucleotide present (0.2 mM ATP), we noted that with M3+/A ratios up to 4: (a) there was a sharp peak in the observed Nred above the level achieved by control F-actin; (b) the magnitude of (a) was shown to be a function of the initial G-actin concentration. With an M3+/A ratio of greater than 4 we observed: (i) a sharp fall in the observed Nred; (ii) the formation of an insoluble aggregate of actin; (iii) the formation of (ii) was completely reversed by removal of the M3+; (iv) a complete inhibition of the ATP hydrolysis which always accompanies the G- to F-actin transition; (v) the number of mol of M3+ required to completely inhibit the rise in Nred (above the viscosity of G-actin) was a function of the ionic radii of the 11 lanthanide ions tested; and (vi) the effects described in (i) were not mimicked when the initial protein was in the F form. In the absence of added KCI, divalent cations (e.g. Mg2+) polymerize G-actin but this effect is not mimicked by the addition of the lanthanide ions. However, under these conditions the lanthanide ions cause the formation of an insoluble aggregate of actin. We conclude that with greater than 4 mol of lanthanide ions, G-actin aggregates in a form which contains little or no F-actin and that the lanthanide ion-induced aggregates are therefore different from the Mg2+-induced F-actin paracrystals."} {"id": "PMID:153153", "title": "Structural properties of frog muscle myosin.", "content": "Frog myosin is a labile molecule, undergoing irreversible aggregation and rapid loss of ATPase; however, a procedure is described which provides highly purified myosin, with stable solubility and enzymatic properties, from skeletal muscle of Rana catesbeiana. Frog myosin contains heavy chains and light chains 1, 2, and 3. Light chain 3 is present in excess over light chain 1, and light chain 2 may occur as either, or both, of 2 closely migrating bands. On two-dimensional electrophoresis, light chain 1 generates an isoelectric component with pK 5.60; light chain 2 generates a complex pattern with 3 or 4 major components; and light chain 3 generates 2 major components with pK 5.00 and 4.92. The same subunit composition is obtained for frogs acclimated at 25 and 5 degrees C; however, proteolytic artifacts may occur in myosin preparations purified in the absence of protease inhibitors, especially in warm-acclimated frogs.", "contents": "Structural properties of frog muscle myosin. Frog myosin is a labile molecule, undergoing irreversible aggregation and rapid loss of ATPase; however, a procedure is described which provides highly purified myosin, with stable solubility and enzymatic properties, from skeletal muscle of Rana catesbeiana. Frog myosin contains heavy chains and light chains 1, 2, and 3. Light chain 3 is present in excess over light chain 1, and light chain 2 may occur as either, or both, of 2 closely migrating bands. On two-dimensional electrophoresis, light chain 1 generates an isoelectric component with pK 5.60; light chain 2 generates a complex pattern with 3 or 4 major components; and light chain 3 generates 2 major components with pK 5.00 and 4.92. The same subunit composition is obtained for frogs acclimated at 25 and 5 degrees C; however, proteolytic artifacts may occur in myosin preparations purified in the absence of protease inhibitors, especially in warm-acclimated frogs."} {"id": "PMID:153154", "title": "The yeast mitochondrial ATPase complex. Subunit composition and evidence for a latent protease contaminant.", "content": "1. The subunit compositions of the F1 (oligomycin-insensitive) and F1--F0 (oligomycin-sensitive) mitochondrial ATPase complexes from Saccharomyces cerevisiae have been examined by the highly resolving technique of sodium dodecyl sulphate-polyacrylamide slab gel electrophoresis using a discontinuous buffer system. When isolated in the presence of protease inhibitors, F1 and F1--F0 contained five and twelve bands, respectively; this contrasts with the four- and ten-band patterns seen previously using the less resolving disc gel method. When isolated in the absence of protease inhibitors both F1 and F1--F0 contain spurious polypeptides produced by proteolytic modification. 2. Endogenous protein turnover in S. cerevisiae was impaired in the presence of protease inhibitors. F1--F0 isolated from cells grown in the presence and absence of inhibitors contained an identical polypeptide composition, suggesting that the subunits are not significantly modified by endogenous proteases prior to cell harvesting. 3. Yeast F1--F0 prepared in the presence of protease inhibitors contains a latent, sodium dodecyl sulphate-activated protease contaminant. Sodium dodecyl sulphate-induced proteolysis is largely confined to the 52 000 dalton alpha subunit which degrades into polypeptides of 40 000 and 10 700 daltons. The 40 000 dalton band is apparently equivalent to the polypeptide previously designated subunit 3. 4. Both F1 and F1--F0 were isolated from Torulopsis glabrata, a yeast with considerably shorter mitochondrial DNA than that in S. cerevisiae. F1--F0 catalysed high rates of ATP--32Pi exchange when reconstituted into phospholipid vesicles, thus demonstrating the presence of a complete coupling mechanism. F1--F0 contained approximately twelve subunits and F1 five, like the S. cerevisiae complexes. It therefore appears that the shorter mitochondrial DNA length does not produce a significantly simpler ATPase subunit structure.", "contents": "The yeast mitochondrial ATPase complex. Subunit composition and evidence for a latent protease contaminant. 1. The subunit compositions of the F1 (oligomycin-insensitive) and F1--F0 (oligomycin-sensitive) mitochondrial ATPase complexes from Saccharomyces cerevisiae have been examined by the highly resolving technique of sodium dodecyl sulphate-polyacrylamide slab gel electrophoresis using a discontinuous buffer system. When isolated in the presence of protease inhibitors, F1 and F1--F0 contained five and twelve bands, respectively; this contrasts with the four- and ten-band patterns seen previously using the less resolving disc gel method. When isolated in the absence of protease inhibitors both F1 and F1--F0 contain spurious polypeptides produced by proteolytic modification. 2. Endogenous protein turnover in S. cerevisiae was impaired in the presence of protease inhibitors. F1--F0 isolated from cells grown in the presence and absence of inhibitors contained an identical polypeptide composition, suggesting that the subunits are not significantly modified by endogenous proteases prior to cell harvesting. 3. Yeast F1--F0 prepared in the presence of protease inhibitors contains a latent, sodium dodecyl sulphate-activated protease contaminant. Sodium dodecyl sulphate-induced proteolysis is largely confined to the 52 000 dalton alpha subunit which degrades into polypeptides of 40 000 and 10 700 daltons. The 40 000 dalton band is apparently equivalent to the polypeptide previously designated subunit 3. 4. Both F1 and F1--F0 were isolated from Torulopsis glabrata, a yeast with considerably shorter mitochondrial DNA than that in S. cerevisiae. F1--F0 catalysed high rates of ATP--32Pi exchange when reconstituted into phospholipid vesicles, thus demonstrating the presence of a complete coupling mechanism. F1--F0 contained approximately twelve subunits and F1 five, like the S. cerevisiae complexes. It therefore appears that the shorter mitochondrial DNA length does not produce a significantly simpler ATPase subunit structure."} {"id": "PMID:153155", "title": "Immunological and reconstitution studies on the adenosine triphosphatase complex from Rhodospirillum rubrum.", "content": "Studies on restoration of membrane-bound adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3) from Rhodospirillum rubrum show that the delta-subunit is capable of binding to the F1 factor or to the F0 moiety of the F0-F1 ATPase complex. This subunit is thus likely involved in linking the F0 and F1 factor. During solubilization of the oligomycin-sensitive F0-F1 ATPase complex with Triton X-100 the detergent becomes specifically associated with the lipophilic F0 part of the enzyme complex. Crossed immunoelectrophoresis, agglutination tests, and kinetic studies with anti-F1 ATPase antibodies reveal a reaction of immunological identity of membrane-bound ATPase, F0-F1 ATPase, and F1 ATPase.", "contents": "Immunological and reconstitution studies on the adenosine triphosphatase complex from Rhodospirillum rubrum. Studies on restoration of membrane-bound adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3) from Rhodospirillum rubrum show that the delta-subunit is capable of binding to the F1 factor or to the F0 moiety of the F0-F1 ATPase complex. This subunit is thus likely involved in linking the F0 and F1 factor. During solubilization of the oligomycin-sensitive F0-F1 ATPase complex with Triton X-100 the detergent becomes specifically associated with the lipophilic F0 part of the enzyme complex. Crossed immunoelectrophoresis, agglutination tests, and kinetic studies with anti-F1 ATPase antibodies reveal a reaction of immunological identity of membrane-bound ATPase, F0-F1 ATPase, and F1 ATPase."} {"id": "PMID:153156", "title": "Precocious aging and dementia in patients with Down's syndrome.", "content": "Fifty unselected institutionalized patients with Down's syndrome were studied to determine the clinical course of precocious aging and mental and neurological deterioration. In our studies we establish statistically significant differences in neurological and psychiatric abnormalities and mental deterioration in patients below and above age 35, indicating progressive changes in the central nervous system. We demonstrate higher incidence of recent memory loss, impairment of short-term visual retention, frontal release signs, hypertonia, hyperreflexia, long-tract signs, and psychiatric problems. We also note the presence of external features of precocious aging. Down's syndrome appears to be a human chromosomal abnormality in which genetically determined biochemical defects leading to precocious aging and dementia can be studied.", "contents": "Precocious aging and dementia in patients with Down's syndrome. Fifty unselected institutionalized patients with Down's syndrome were studied to determine the clinical course of precocious aging and mental and neurological deterioration. In our studies we establish statistically significant differences in neurological and psychiatric abnormalities and mental deterioration in patients below and above age 35, indicating progressive changes in the central nervous system. We demonstrate higher incidence of recent memory loss, impairment of short-term visual retention, frontal release signs, hypertonia, hyperreflexia, long-tract signs, and psychiatric problems. We also note the presence of external features of precocious aging. Down's syndrome appears to be a human chromosomal abnormality in which genetically determined biochemical defects leading to precocious aging and dementia can be studied."} {"id": "PMID:153163", "title": "[Study on the pineal gland of ungulates].", "content": "Study of the pineal gland of 91 Ungulates belonging to 55 species shows the constant presence of calcarine concretions of various importance. These concretions develop in the walls of vessels that first undergo a preliminary transformation characterized by the presence of alcian blue or PAS positive substances. In nearly all cases, the presence of alcian blue positive cells with processes (distinct from mastocytes) can be found in the pineal gland of ungulates. These elements sometimes contain fine calcarine granulations that probably are the site of origin of acervuli. These observations were extended to several marsupials, carnivora, pinnipeda and perissodactyles.", "contents": "[Study on the pineal gland of ungulates]. Study of the pineal gland of 91 Ungulates belonging to 55 species shows the constant presence of calcarine concretions of various importance. These concretions develop in the walls of vessels that first undergo a preliminary transformation characterized by the presence of alcian blue or PAS positive substances. In nearly all cases, the presence of alcian blue positive cells with processes (distinct from mastocytes) can be found in the pineal gland of ungulates. These elements sometimes contain fine calcarine granulations that probably are the site of origin of acervuli. These observations were extended to several marsupials, carnivora, pinnipeda and perissodactyles."} {"id": "PMID:153166", "title": "[Lead and cadmium toxicity in established mammalian cell lines].", "content": "Lead and cadmium toxicity was evaluated in three mammalian cell lines (tumour : HeLa, transformed : XC and normal : NRK) by means of the modifications of the 3H-TdR incorporation rate in the nucleus of the treated cells. The three cell lines showed different degrees of sensitivity. Sensitivity depended on the line, metal, its concentration and duration of incubation. Cadmium was found to be at least five times more toxic than lead except at low concentration. The normal cell line was more sensitive to cadmium and less sensitive to lead than other lines.", "contents": "[Lead and cadmium toxicity in established mammalian cell lines]. Lead and cadmium toxicity was evaluated in three mammalian cell lines (tumour : HeLa, transformed : XC and normal : NRK) by means of the modifications of the 3H-TdR incorporation rate in the nucleus of the treated cells. The three cell lines showed different degrees of sensitivity. Sensitivity depended on the line, metal, its concentration and duration of incubation. Cadmium was found to be at least five times more toxic than lead except at low concentration. The normal cell line was more sensitive to cadmium and less sensitive to lead than other lines."} {"id": "PMID:153167", "title": "[A new effect of carbon dioxide: transformation of subsocial species of insects by chronic treatment].", "content": "The carbon dioxide is used to chronic treatment of one minute per day during all the larval life time. This treatment must be distinguished from all those previously described. Subsocial species are changed into their solitary form, although they live in group. The comparison of the pigmentation with slightly or non subsocial species seems to indicate that this effect is linked with the subsocial state. The results are discussed on the basis of nervous and endocrine functionning.", "contents": "[A new effect of carbon dioxide: transformation of subsocial species of insects by chronic treatment]. The carbon dioxide is used to chronic treatment of one minute per day during all the larval life time. This treatment must be distinguished from all those previously described. Subsocial species are changed into their solitary form, although they live in group. The comparison of the pigmentation with slightly or non subsocial species seems to indicate that this effect is linked with the subsocial state. The results are discussed on the basis of nervous and endocrine functionning."} {"id": "PMID:153168", "title": "[Aggression toward groups of male and female OF1 mice by a male congenere and survival to acute hypoxia].", "content": "In OF1 mice, a 107 day-old mouse, isolated since 51 days, acts as an \"aggressor\" when introduced into a group of 10 males or into a group of 10 females of the age of 51 days. This results in fights and flights in the males' group and in copulations in the females' group. In 31 experiments, each performed on a total of 40 males and 40 females, it was observed that an acute DL50 hypoxia (inhalation of nitrogen) provokes a mortality significantly (p less than 0.001) higher in the male \"aggressors\" (95.16%) than in the groups of 10 aggressed mice (mortality: 64.26% for the males' groups and 52.65% for the females groups). Besides, compared to control groups without male \"aggressor\", the introduction of the male congener significantly (p less than 0.001) increases the acute hypoxic mortality in the females' but not in the males' groups.", "contents": "[Aggression toward groups of male and female OF1 mice by a male congenere and survival to acute hypoxia]. In OF1 mice, a 107 day-old mouse, isolated since 51 days, acts as an \"aggressor\" when introduced into a group of 10 males or into a group of 10 females of the age of 51 days. This results in fights and flights in the males' group and in copulations in the females' group. In 31 experiments, each performed on a total of 40 males and 40 females, it was observed that an acute DL50 hypoxia (inhalation of nitrogen) provokes a mortality significantly (p less than 0.001) higher in the male \"aggressors\" (95.16%) than in the groups of 10 aggressed mice (mortality: 64.26% for the males' groups and 52.65% for the females groups). Besides, compared to control groups without male \"aggressor\", the introduction of the male congener significantly (p less than 0.001) increases the acute hypoxic mortality in the females' but not in the males' groups."} {"id": "PMID:153169", "title": "[Method for analysis and measurement of behavior. Application to total nocturnal activity of the rat].", "content": "A long behavior period, as the night activity of rats is transcribed in two graphs which are described by eight parameters. All these parameters are stable for the same animal, but five of them have a few variations between different rats. The behavior changes then appear to be quantifiable.", "contents": "[Method for analysis and measurement of behavior. Application to total nocturnal activity of the rat]. A long behavior period, as the night activity of rats is transcribed in two graphs which are described by eight parameters. All these parameters are stable for the same animal, but five of them have a few variations between different rats. The behavior changes then appear to be quantifiable."} {"id": "PMID:153170", "title": "[Action of the testosterone treated chicken testis on the regression of the M\u00fcllerian duct].", "content": "After administration of testosterone propionate to male chick embryos and chickens, their testis have an activity, on the retrogression of mullerian ducts, much more important than that observed in testis of normal subjects of the same age, activity measured by grafting testis fragments in undifferentiated female chick embryos. The results suggest that testosterone gives such an effect by inhibiting pituitary gonadotropins, peculiarly FSH.", "contents": "[Action of the testosterone treated chicken testis on the regression of the M\u00fcllerian duct]. After administration of testosterone propionate to male chick embryos and chickens, their testis have an activity, on the retrogression of mullerian ducts, much more important than that observed in testis of normal subjects of the same age, activity measured by grafting testis fragments in undifferentiated female chick embryos. The results suggest that testosterone gives such an effect by inhibiting pituitary gonadotropins, peculiarly FSH."} {"id": "PMID:153171", "title": "[Repartition of the kidney cortex glomerulus in rats].", "content": "This paper presents the repartition of 989 glomeruli in 8 parallel concentric renal cortex zones, by projecting on a calibrated screen rat kidney slices photographies. The glomerular density increases regularly from the outside to the middle cortical zones and then decreases to the deepest juxtamedullary zones.", "contents": "[Repartition of the kidney cortex glomerulus in rats]. This paper presents the repartition of 989 glomeruli in 8 parallel concentric renal cortex zones, by projecting on a calibrated screen rat kidney slices photographies. The glomerular density increases regularly from the outside to the middle cortical zones and then decreases to the deepest juxtamedullary zones."} {"id": "PMID:153172", "title": "[Comparative effect of theophylline on urinary protein excretion in rats during diurnal and nocturanal periods].", "content": "In 3 lots of 15 rats, urinary proteins excretion (U.P.E.) during 6 hours periods is compared : 1) daily and nightly in physiological conditions, where U.P.E. increases nightly (+ 97,47%) : 2) daily, before and after theophylline injection, where U.P.E. increases after theophylline injection (+ 78,62%) ; 3) nightly, before and after theophylline injection, where U.P.E. increase is only tiny (+ 3,53%) after theophylline injection. So, in nightly physiological and in daily experimental conditions the important U.P.E. increases can be in part explained by those of renal functions. This result can explain after nightly theophylline injection (where renal functions are already very higher than in daily period) the so small nightly proteinuria increase with the xanthic diuretic ; it cannot be compared to the daily value, because the renal functions cannot increase beyond some limits. Lastly, the present paper exhibits how a pharmacomolecule (as theophylline here) can act differently daily and nightly and open a new investigation field in chronopharmacology of diuretics.", "contents": "[Comparative effect of theophylline on urinary protein excretion in rats during diurnal and nocturanal periods]. In 3 lots of 15 rats, urinary proteins excretion (U.P.E.) during 6 hours periods is compared : 1) daily and nightly in physiological conditions, where U.P.E. increases nightly (+ 97,47%) : 2) daily, before and after theophylline injection, where U.P.E. increases after theophylline injection (+ 78,62%) ; 3) nightly, before and after theophylline injection, where U.P.E. increase is only tiny (+ 3,53%) after theophylline injection. So, in nightly physiological and in daily experimental conditions the important U.P.E. increases can be in part explained by those of renal functions. This result can explain after nightly theophylline injection (where renal functions are already very higher than in daily period) the so small nightly proteinuria increase with the xanthic diuretic ; it cannot be compared to the daily value, because the renal functions cannot increase beyond some limits. Lastly, the present paper exhibits how a pharmacomolecule (as theophylline here) can act differently daily and nightly and open a new investigation field in chronopharmacology of diuretics."} {"id": "PMID:153173", "title": "[Enhancement of growth of rat liver cell cultures by lithocholic acid].", "content": "Lithocholic acid enhances the growth of 4 independent lines of liver cells, but is toxic to colon cancer cells and fibroblasts in culture. Cholic acid does not affect the growth of liver cells, deoxycholic and chenodexoycholic acids are highly toxic to them.", "contents": "[Enhancement of growth of rat liver cell cultures by lithocholic acid]. Lithocholic acid enhances the growth of 4 independent lines of liver cells, but is toxic to colon cancer cells and fibroblasts in culture. Cholic acid does not affect the growth of liver cells, deoxycholic and chenodexoycholic acids are highly toxic to them."} {"id": "PMID:153174", "title": "[Utilization of free fatty acids and triglycerides by the perfused isolated rat heart after a prolonged swimming training program].", "content": "The effects of swimming training upon mechanical and metabolic properties of heart are investigated in two groups of male Sprague Dawley rats, fed ad libitum: a control group and a swimming group. The chronic training improves myocardial mechanical performances: coronary flow, cardiac output and left ventricular pressure are increased in isolated working conditioned heart preparations. Oxygen consumption and work performance are greater than in control group, but cardiac efficiency is not significantly different between the two groups. Intrinsic conditioned heart rate is lower than in control heart. Endogenous triglycerides and exogenous FFA utilization rates are increased in trained perfused heart. We found a significant correlation (P less than 0,01) between exogenous FFA utilisation and coronary flow.", "contents": "[Utilization of free fatty acids and triglycerides by the perfused isolated rat heart after a prolonged swimming training program]. The effects of swimming training upon mechanical and metabolic properties of heart are investigated in two groups of male Sprague Dawley rats, fed ad libitum: a control group and a swimming group. The chronic training improves myocardial mechanical performances: coronary flow, cardiac output and left ventricular pressure are increased in isolated working conditioned heart preparations. Oxygen consumption and work performance are greater than in control group, but cardiac efficiency is not significantly different between the two groups. Intrinsic conditioned heart rate is lower than in control heart. Endogenous triglycerides and exogenous FFA utilization rates are increased in trained perfused heart. We found a significant correlation (P less than 0,01) between exogenous FFA utilisation and coronary flow."} {"id": "PMID:153175", "title": "[Effect of separated or simultaneous ingestion of tannic acid, potassium metabisulfite and ethanol on reproduction in rats].", "content": "As compared to controls, female rats fed a diet containing 3.2% of tannic acid have a higher fertility index, but the number of their born alive young is smaller and the growth of their litters is slower. A diet containing 1% of potassium metabisulfite also decreases the growth rate of the litters. These effects are additives. Ethanol (fed at a level of 30 cal. % at the expense of carbohydrates) has no effect on the reproduction performances and does not interact with the previous effects.", "contents": "[Effect of separated or simultaneous ingestion of tannic acid, potassium metabisulfite and ethanol on reproduction in rats]. As compared to controls, female rats fed a diet containing 3.2% of tannic acid have a higher fertility index, but the number of their born alive young is smaller and the growth of their litters is slower. A diet containing 1% of potassium metabisulfite also decreases the growth rate of the litters. These effects are additives. Ethanol (fed at a level of 30 cal. % at the expense of carbohydrates) has no effect on the reproduction performances and does not interact with the previous effects."} {"id": "PMID:153176", "title": "[Comparative effects of hydrolizable or condensed tannins on the liver reserve of vitamin A in rats].", "content": "A 10 weeks study in rats fed a balanced diet containing \"hydrosoluble\" vitamin A and 3,2 p. 100 by weight of tannic acid resulted in a marked decrease of the hepatic concentration of vitamin A. The same dietary dose of chestnut tree tannins resulted in a much more marked decrease. However, there was no effect of a quebracho extract (condensed tannins) given in the same conditions.", "contents": "[Comparative effects of hydrolizable or condensed tannins on the liver reserve of vitamin A in rats]. A 10 weeks study in rats fed a balanced diet containing \"hydrosoluble\" vitamin A and 3,2 p. 100 by weight of tannic acid resulted in a marked decrease of the hepatic concentration of vitamin A. The same dietary dose of chestnut tree tannins resulted in a much more marked decrease. However, there was no effect of a quebracho extract (condensed tannins) given in the same conditions."} {"id": "PMID:153177", "title": "[Melatonin and gonadoliberin (LH-RH) cells in rat hypothalamus].", "content": "Immature female rats were induced to ovulate by an injection of pregnant mare serum: melatonin, intraperitonealy injected, induce an increase of LH-RH immunoreactive neurons in the hypothalamus. These neurons are localized in septo preoptic, infundibular and premammillary areas.", "contents": "[Melatonin and gonadoliberin (LH-RH) cells in rat hypothalamus]. Immature female rats were induced to ovulate by an injection of pregnant mare serum: melatonin, intraperitonealy injected, induce an increase of LH-RH immunoreactive neurons in the hypothalamus. These neurons are localized in septo preoptic, infundibular and premammillary areas."} {"id": "PMID:153178", "title": "[Effect of fatigue on the compliance series of isolated muscles].", "content": "Frog sartorius muscles are stretched at rest and during tetanic contractions, and series-compliance of normal muscle is compared to that of a fatigued one. The series-compliance is calculated from the parallel compliance and the active one. The compliance decreases when the tension increases and becomes quite constant for the highest levels of tension. These results are discussed on the basis of the sliding filaments theory.", "contents": "[Effect of fatigue on the compliance series of isolated muscles]. Frog sartorius muscles are stretched at rest and during tetanic contractions, and series-compliance of normal muscle is compared to that of a fatigued one. The series-compliance is calculated from the parallel compliance and the active one. The compliance decreases when the tension increases and becomes quite constant for the highest levels of tension. These results are discussed on the basis of the sliding filaments theory."} {"id": "PMID:153179", "title": "[Bronchopulmonary lymphocytes and their B and T subpopulations in control and experimental influenza infected mice].", "content": "Immunofluorescent studies showed that, whereas the total number of lymphocytes was still increased on the third and fourth weeks of experimental airborne influenza, the B/T cell ratio remained in the same range as in control animals. This ratio is comparable to results with mouse peripheral lymph nodes.", "contents": "[Bronchopulmonary lymphocytes and their B and T subpopulations in control and experimental influenza infected mice]. Immunofluorescent studies showed that, whereas the total number of lymphocytes was still increased on the third and fourth weeks of experimental airborne influenza, the B/T cell ratio remained in the same range as in control animals. This ratio is comparable to results with mouse peripheral lymph nodes."} {"id": "PMID:153180", "title": "[Chronopharmacology of pancuronium in rats anesthetized by CT 1341 (Alfat\u00e9sine)].", "content": "A circadian variation in the curarizing ability of pancuronium bromide (Pavulon) has been documented in an homogenous group of 100 Wistar AF-SPF adult male rats anaesthetized by the steroid anaesthetic althesin (Alfat\u00e9sine, CT 1341). Animals were maintained at 24 +/- 2 degrees C and synchronized with natural light 06.00 to 18.00 and darkness (october 1977). We observed significant circadian rhythms for both of these agents: first the induction of anaesthesia by althesin was markedly pronounced at 15.30 and varied with season. Secondly the maximum effect of pancuronium was recorded at 08.00. When rats were anaesthetized by sodium pentobarbital under similar experimental conditions but during a different season (january to may) we observed a similar circadian rhythm for pancuronium. These data indicate that: a) the type of anaesthesia used in the protocol may not be of importance in demonstration of a curarizing rhythm in the rat but, b) the possibility of a seasonal component being present and effecting this rhythm needs to be investigated.", "contents": "[Chronopharmacology of pancuronium in rats anesthetized by CT 1341 (Alfat\u00e9sine)]. A circadian variation in the curarizing ability of pancuronium bromide (Pavulon) has been documented in an homogenous group of 100 Wistar AF-SPF adult male rats anaesthetized by the steroid anaesthetic althesin (Alfat\u00e9sine, CT 1341). Animals were maintained at 24 +/- 2 degrees C and synchronized with natural light 06.00 to 18.00 and darkness (october 1977). We observed significant circadian rhythms for both of these agents: first the induction of anaesthesia by althesin was markedly pronounced at 15.30 and varied with season. Secondly the maximum effect of pancuronium was recorded at 08.00. When rats were anaesthetized by sodium pentobarbital under similar experimental conditions but during a different season (january to may) we observed a similar circadian rhythm for pancuronium. These data indicate that: a) the type of anaesthesia used in the protocol may not be of importance in demonstration of a curarizing rhythm in the rat but, b) the possibility of a seasonal component being present and effecting this rhythm needs to be investigated."} {"id": "PMID:153181", "title": "[Diabetes insipidus and exogenous antidiuretic hormone activity modifications by lithium in the rat].", "content": "The authors made conspicuous in the rat the appearance of \"diabetes insipidus\" induced by two lithium salts: chloride and carbonate administered orally, with increasing doses in food. The polyuria, polydipsia and urinary hypotony are reversible and disappeared with stopping the treatment. The animals became insensible to the exogenous antidiuretic hormon during the treatment and progressively became sensible again during the following twenty days so suggesting a nephrogenic mechanism by lithium: either a loss of ADH activity, either the abolition of intrarenal osmotic pressure gradient.", "contents": "[Diabetes insipidus and exogenous antidiuretic hormone activity modifications by lithium in the rat]. The authors made conspicuous in the rat the appearance of \"diabetes insipidus\" induced by two lithium salts: chloride and carbonate administered orally, with increasing doses in food. The polyuria, polydipsia and urinary hypotony are reversible and disappeared with stopping the treatment. The animals became insensible to the exogenous antidiuretic hormon during the treatment and progressively became sensible again during the following twenty days so suggesting a nephrogenic mechanism by lithium: either a loss of ADH activity, either the abolition of intrarenal osmotic pressure gradient."} {"id": "PMID:153182", "title": "[Comparison of the cytotoxicity of chloroform on mouse L cells by measurement of proteins and chromium 51 release].", "content": "The authors describe a new cytotoxicity test based on the classical measurement of the residual proteins after a contact time of 4 days between the produit tested and the mouse L cells. The results are expressed as a cytotoxic dose 50 with a confidence limit for the 95% threshold after a statistical treatment of the analytical data by a computerized method. For chloroform, this method is more sensitive that the classical cytotoxicity test involving the chrom 51 release.", "contents": "[Comparison of the cytotoxicity of chloroform on mouse L cells by measurement of proteins and chromium 51 release]. The authors describe a new cytotoxicity test based on the classical measurement of the residual proteins after a contact time of 4 days between the produit tested and the mouse L cells. The results are expressed as a cytotoxic dose 50 with a confidence limit for the 95% threshold after a statistical treatment of the analytical data by a computerized method. For chloroform, this method is more sensitive that the classical cytotoxicity test involving the chrom 51 release."} {"id": "PMID:153183", "title": "[Ultrastructural cytochemistry of human spermatozoa].", "content": "Enzymatic activities and repartition of glycoproteins were studied with electron microscopy in human ejaculated spermatozoa. Enzymatic activities are localised in the head of spermatozoon: arylsulfatase in the acrosome, acid phosphatase in the periacrosomal cytoplasm. Phosphotungstic acid at low pH and collo\u00efdal iron allow detection of glycoproteins and acid groups on the sperm cell surface. Glycoproteins are present in the acrosome. These results are slightly different to those obtained in other species.", "contents": "[Ultrastructural cytochemistry of human spermatozoa]. Enzymatic activities and repartition of glycoproteins were studied with electron microscopy in human ejaculated spermatozoa. Enzymatic activities are localised in the head of spermatozoon: arylsulfatase in the acrosome, acid phosphatase in the periacrosomal cytoplasm. Phosphotungstic acid at low pH and collo\u00efdal iron allow detection of glycoproteins and acid groups on the sperm cell surface. Glycoproteins are present in the acrosome. These results are slightly different to those obtained in other species."} {"id": "PMID:153184", "title": "[Effect of an MAO inhibitor, phenelzine, on acetylation of isoniazid by isolated perfused rat liver].", "content": "Phenelzin, a monoamine oxydase inhibitor, administered in vivo, in rats, slowed down the initial velocity of isoniazid acetylation in isolated perfused liver. After in vitro addition in perfusion medium phenelzin decreased as well the initial velocity of acetylation as the total amount of acetylated substrate.", "contents": "[Effect of an MAO inhibitor, phenelzine, on acetylation of isoniazid by isolated perfused rat liver]. Phenelzin, a monoamine oxydase inhibitor, administered in vivo, in rats, slowed down the initial velocity of isoniazid acetylation in isolated perfused liver. After in vitro addition in perfusion medium phenelzin decreased as well the initial velocity of acetylation as the total amount of acetylated substrate."} {"id": "PMID:153185", "title": "[Localization of N-acetyltransferases in sinusoidal liver cells. Effect of zymosan on the acetylation of sulfamethazine and isoniazid in the rat and in isolated perfused liver].", "content": "N-acetyltransferase (NAT) have been demonstrated to be localized in sinuso\u00efdal cells and not in hepatocytes. Acetylation activities increased after pretreatment with Zymosan (40 mg/kg, i.v., 24 h before phenotyping) as well in vivo and in isolated perfused liver and in cytosolic fractions prepared from several rats organs. These data favor the localization of NAT-activity in reticulo-endothelial system. Increased protein levels in liver, gut, spleen and lungs cytosolic fractions (100 000 g, 120 mn) 48 h after Zymosan administration, suggest and inducing effect of this drug on NAT activity.", "contents": "[Localization of N-acetyltransferases in sinusoidal liver cells. Effect of zymosan on the acetylation of sulfamethazine and isoniazid in the rat and in isolated perfused liver]. N-acetyltransferase (NAT) have been demonstrated to be localized in sinuso\u00efdal cells and not in hepatocytes. Acetylation activities increased after pretreatment with Zymosan (40 mg/kg, i.v., 24 h before phenotyping) as well in vivo and in isolated perfused liver and in cytosolic fractions prepared from several rats organs. These data favor the localization of NAT-activity in reticulo-endothelial system. Increased protein levels in liver, gut, spleen and lungs cytosolic fractions (100 000 g, 120 mn) 48 h after Zymosan administration, suggest and inducing effect of this drug on NAT activity."} {"id": "PMID:153186", "title": "[Bioconversion of steroids in mutants of Nocardia restrictus].", "content": "Nocardia restrictus grows quickly on synthetic media containing different carbonated substrates (steroids, organic acids). The control of growth parameters of this microbial species allowed the development of the production and selection methodology for mutants unable to grow on androst-4\u00e8ne-3,17-dione. A stable mutant convert androst-4-\u00e8ne-3,17-dione in perhydroindan propionic acid without addition of any degradation inhibitor in the medium.", "contents": "[Bioconversion of steroids in mutants of Nocardia restrictus]. Nocardia restrictus grows quickly on synthetic media containing different carbonated substrates (steroids, organic acids). The control of growth parameters of this microbial species allowed the development of the production and selection methodology for mutants unable to grow on androst-4\u00e8ne-3,17-dione. A stable mutant convert androst-4-\u00e8ne-3,17-dione in perhydroindan propionic acid without addition of any degradation inhibitor in the medium."} {"id": "PMID:153187", "title": "[Modifications of oxygen consumption in the ant Dolichoderus quadripunctatus exposed to very powerful gamma irradiation].", "content": "The oxygen consumption of irradiated workers ants of Dolichoderus quadripunctatus, shows a significant increase when ants received a hight dose (50 000 or 100 000 Rad) of gamma rays.", "contents": "[Modifications of oxygen consumption in the ant Dolichoderus quadripunctatus exposed to very powerful gamma irradiation]. The oxygen consumption of irradiated workers ants of Dolichoderus quadripunctatus, shows a significant increase when ants received a hight dose (50 000 or 100 000 Rad) of gamma rays."} {"id": "PMID:153188", "title": "[Chromosomal structure or porcine lymphocytes effected by food additives].", "content": "Different concentrations of food additives were introduced in cultures of pig lymphocytes. No special chromosomal damage were induced by anticoccidians. On the contrary some antibiotics caused chromosomic anomalies. Chloramphenicol and furazolidone assayed in vitro and in vivo had also an antimitotic effect. The purpose of this work was to know the cytotoxic effect of some substances: a preliminary and cheap test could be a cytogenetic examination in vitro.", "contents": "[Chromosomal structure or porcine lymphocytes effected by food additives]. Different concentrations of food additives were introduced in cultures of pig lymphocytes. No special chromosomal damage were induced by anticoccidians. On the contrary some antibiotics caused chromosomic anomalies. Chloramphenicol and furazolidone assayed in vitro and in vivo had also an antimitotic effect. The purpose of this work was to know the cytotoxic effect of some substances: a preliminary and cheap test could be a cytogenetic examination in vitro."} {"id": "PMID:153189", "title": "[Changes in the digestibility of constituents of the diet in the rabbit].", "content": "Fiber digestibility of two diets (the first based on alfalfa dried, the second based on beet-pulp dried) with the same level of crude fiber and crude protein was measured on rabbits of 6, 7, 11, 13 and 17 weeks old. The age has no significative effect on digestibility (dry matter, organic matter, crude fiber) of the two experimental diets. The quantity of cellulose and hemicellulose digested was greater in rabbits on the pulp diet. Independantly of the diet hemicellulose is more digestible than cellulose. Expediency of use other analytical test than crude fiber in the nutritional requirements of rabbits is discussed.", "contents": "[Changes in the digestibility of constituents of the diet in the rabbit]. Fiber digestibility of two diets (the first based on alfalfa dried, the second based on beet-pulp dried) with the same level of crude fiber and crude protein was measured on rabbits of 6, 7, 11, 13 and 17 weeks old. The age has no significative effect on digestibility (dry matter, organic matter, crude fiber) of the two experimental diets. The quantity of cellulose and hemicellulose digested was greater in rabbits on the pulp diet. Independantly of the diet hemicellulose is more digestible than cellulose. Expediency of use other analytical test than crude fiber in the nutritional requirements of rabbits is discussed."} {"id": "PMID:153190", "title": "[Comparison of the diuretic and natriuretic effects of dopamine in control and diabetes insipidus dogs. Effect of propranolol].", "content": "The diuretic effect of dopamine is unchanged in the dog with diabetes insipidus but the natriuretic effect of dopamine is shorter. With the normal dog propanolol delays the dopamine-induced diuresis and natriuresis but the magnitude of this double effect is unchanged. In the dog with diabetes insipidus, propanolol suppresses the dopaminergic diuresis and reduces the natriuresis.", "contents": "[Comparison of the diuretic and natriuretic effects of dopamine in control and diabetes insipidus dogs. Effect of propranolol]. The diuretic effect of dopamine is unchanged in the dog with diabetes insipidus but the natriuretic effect of dopamine is shorter. With the normal dog propanolol delays the dopamine-induced diuresis and natriuresis but the magnitude of this double effect is unchanged. In the dog with diabetes insipidus, propanolol suppresses the dopaminergic diuresis and reduces the natriuresis."} {"id": "PMID:153191", "title": "[Effects of an extract of adult rat liver on Reuber H-35 hepatoma cells in vitro].", "content": "The effects of an extract from adult liver on hepatoma cells cultivated in vitro (line H-35) are studied with cytological and quantitative cytochemical methods. This extract inhibits cell multiplication and premitotic DNA synthesis. The treated cells form \"trabeculae\" looking like those observed when normal adult hepatocytes are cultivated in vitro.", "contents": "[Effects of an extract of adult rat liver on Reuber H-35 hepatoma cells in vitro]. The effects of an extract from adult liver on hepatoma cells cultivated in vitro (line H-35) are studied with cytological and quantitative cytochemical methods. This extract inhibits cell multiplication and premitotic DNA synthesis. The treated cells form \"trabeculae\" looking like those observed when normal adult hepatocytes are cultivated in vitro."} {"id": "PMID:153192", "title": "[The cause of slow increase of heart rate during muscular exercise in man].", "content": "The slow increase in heart rate which is observed in normal man submitted to heavy muscular exercise is due for a part to an activation of orthosympathetic cardiac activity which is blocked by beta antagonists. It is also explained by direct action of hyperthermia on the heart.", "contents": "[The cause of slow increase of heart rate during muscular exercise in man]. The slow increase in heart rate which is observed in normal man submitted to heavy muscular exercise is due for a part to an activation of orthosympathetic cardiac activity which is blocked by beta antagonists. It is also explained by direct action of hyperthermia on the heart."} {"id": "PMID:153193", "title": "[Transmissible resistance factor to cobalt in Pseumononas hydrogenomonas].", "content": "Curable resistance to cobalt, zinc and cadmium ions was observed in a hydrogen-utilizing Pseudomonas. Resistance to cobalt was transferred to P. aeruginosa and can be transferred again between P. aeruginosa strains.", "contents": "[Transmissible resistance factor to cobalt in Pseumononas hydrogenomonas]. Curable resistance to cobalt, zinc and cadmium ions was observed in a hydrogen-utilizing Pseudomonas. Resistance to cobalt was transferred to P. aeruginosa and can be transferred again between P. aeruginosa strains."} {"id": "PMID:153194", "title": "[Effect of electro-acupuncture on the response of the trigeminal nucleus evoked by electric stimulation of dental pulp in the cat].", "content": "The potential in the spinal trigeminal nucleus evoked by electrical tooth pulp stimulation is depressed by electro-acupuncture given to the acupuncture point in the course of the nerve innervating the stimulated tooth.", "contents": "[Effect of electro-acupuncture on the response of the trigeminal nucleus evoked by electric stimulation of dental pulp in the cat]. The potential in the spinal trigeminal nucleus evoked by electrical tooth pulp stimulation is depressed by electro-acupuncture given to the acupuncture point in the course of the nerve innervating the stimulated tooth."} {"id": "PMID:153195", "title": "[Inhibition, by electro-acupuncture, of the scalp evoked potential induced by painful stimulation of the tooth in man].", "content": "Scalp potentials evoked by electrical stimulation of the tooth pulp can be diminished in amplitude by electroacupuncture. This diminution goes generally in inverse with the increase in subjective pain threshold.", "contents": "[Inhibition, by electro-acupuncture, of the scalp evoked potential induced by painful stimulation of the tooth in man]. Scalp potentials evoked by electrical stimulation of the tooth pulp can be diminished in amplitude by electroacupuncture. This diminution goes generally in inverse with the increase in subjective pain threshold."} {"id": "PMID:153196", "title": "[Inhibitory effects of dipeptides containing tryptophan on the excitability on the giant neuron of the giant African snail (Achatina fulica, Ferussac)].", "content": "Besides an inhibitory effect of L-Lys-L-Phe-L-Tyr and L-Phe-L-Tyr, L-Phe-L-Trp showed the same effect on the excitability of a giant neurone (the TAN, tonically autoactive neurone) identified in suboesophageal ganglia of Achatina futica F\u00e9russac. The critical concentration of L-Phe-L-Trp to produce the effect was 10(-5)--3 X 10(-5) kg/1. The inhibitory effect of this substance was relatively slow and independent no chloride ions, as well as in the case of L-Phe-L-Tyr. L-Trp-L-Phe, Gly-L-Trp and L-Trp-Gly did not show any effect on the same neurone. The I-V curve of the TAN's neuromembrane, measured by the injection of a transmembrane triangular current, were not modified markedly by L-Phe-L-Trp at 4 X 10(-4) kg/1. The pattern of the TAN's spike firing produced by the depolarizing current injection were not influenced by this substance.", "contents": "[Inhibitory effects of dipeptides containing tryptophan on the excitability on the giant neuron of the giant African snail (Achatina fulica, Ferussac)]. Besides an inhibitory effect of L-Lys-L-Phe-L-Tyr and L-Phe-L-Tyr, L-Phe-L-Trp showed the same effect on the excitability of a giant neurone (the TAN, tonically autoactive neurone) identified in suboesophageal ganglia of Achatina futica F\u00e9russac. The critical concentration of L-Phe-L-Trp to produce the effect was 10(-5)--3 X 10(-5) kg/1. The inhibitory effect of this substance was relatively slow and independent no chloride ions, as well as in the case of L-Phe-L-Tyr. L-Trp-L-Phe, Gly-L-Trp and L-Trp-Gly did not show any effect on the same neurone. The I-V curve of the TAN's neuromembrane, measured by the injection of a transmembrane triangular current, were not modified markedly by L-Phe-L-Trp at 4 X 10(-4) kg/1. The pattern of the TAN's spike firing produced by the depolarizing current injection were not influenced by this substance."} {"id": "PMID:153198", "title": "Suppressor cell activity in cancer patients: a possible role for thymic hormones.", "content": "We have identified the presence of suppressor cell activity in the peripheral blood of immunosuppressed stage IV cancer patients. The patients' cells had a diminished mitogenic response to phytohemagglutinin (PHA) and suppressed the PHA mitogenic response of a normal donor's peripheral blood lymphocytes (PBL). Thus, PBL from a cancer patient whose PHA mitogenic response was 3932 counts per minute (cpm), cultured together with a normal donor's PBL with a PHA mitogenic response of 82,865 net cpm, caused a greater than 50% reduction in the latter (37,651 net cpm). Suppressor cell activity was present in 12 of 14 patients tested. This effect was partially mitigated by irradiation with 4000 rads in nine of 14 patients. Preincubation of the patients' cells with thymosin followed by the addition of thymosin to the co-cultured cells mitigated the suppressor activity in five of ten patients and thymic humoral factor did the same in four of 11 patients. A radiosensitive and thymic hormone-responsive suppressor cell may be present in the peripheral blood of cancer patients. Confirmation of this preliminary observation and further characterization of the cell or cells is currently being undertaken.", "contents": "Suppressor cell activity in cancer patients: a possible role for thymic hormones. We have identified the presence of suppressor cell activity in the peripheral blood of immunosuppressed stage IV cancer patients. The patients' cells had a diminished mitogenic response to phytohemagglutinin (PHA) and suppressed the PHA mitogenic response of a normal donor's peripheral blood lymphocytes (PBL). Thus, PBL from a cancer patient whose PHA mitogenic response was 3932 counts per minute (cpm), cultured together with a normal donor's PBL with a PHA mitogenic response of 82,865 net cpm, caused a greater than 50% reduction in the latter (37,651 net cpm). Suppressor cell activity was present in 12 of 14 patients tested. This effect was partially mitigated by irradiation with 4000 rads in nine of 14 patients. Preincubation of the patients' cells with thymosin followed by the addition of thymosin to the co-cultured cells mitigated the suppressor activity in five of ten patients and thymic humoral factor did the same in four of 11 patients. A radiosensitive and thymic hormone-responsive suppressor cell may be present in the peripheral blood of cancer patients. Confirmation of this preliminary observation and further characterization of the cell or cells is currently being undertaken."} {"id": "PMID:153199", "title": "Immunomodulation with thiabendazole: a review of immunologic properties and efficacy in combined modality cancer therapy.", "content": "Thiabendazole (TBZ) appears to be an immunorestorative agent, demonstrating maximum immunopotentiation in the immunosuppressed host. Initial in vivo and in vitro immune studies indicate that the drug is most effective when given 24 hours prior to or at the time of administration of antigen. Single doses are more effective than multiple daily doses. One cell population potentiated by TBZ is the macrophage, either by direct activation or secondary to increased lymphokine production. As an adjuvant to conventional cancer treatment modalities, TBZ needs the same host setting as seen with many immunopotentiators. Tumor bulk must be reduced by the primary modality. A dose schedule must be developed in conjunction with each primary modality employed, ie, timing is critical. As an adjuvant in cancer therapy, the drug is most effective when given every other day. Depending upon the primary modality employed, adjuvant TBZ may require dose adjustment.", "contents": "Immunomodulation with thiabendazole: a review of immunologic properties and efficacy in combined modality cancer therapy. Thiabendazole (TBZ) appears to be an immunorestorative agent, demonstrating maximum immunopotentiation in the immunosuppressed host. Initial in vivo and in vitro immune studies indicate that the drug is most effective when given 24 hours prior to or at the time of administration of antigen. Single doses are more effective than multiple daily doses. One cell population potentiated by TBZ is the macrophage, either by direct activation or secondary to increased lymphokine production. As an adjuvant to conventional cancer treatment modalities, TBZ needs the same host setting as seen with many immunopotentiators. Tumor bulk must be reduced by the primary modality. A dose schedule must be developed in conjunction with each primary modality employed, ie, timing is critical. As an adjuvant in cancer therapy, the drug is most effective when given every other day. Depending upon the primary modality employed, adjuvant TBZ may require dose adjustment."} {"id": "PMID:153212", "title": "[Suppression of the mixed lymphocytic reaction by autologous red cells and their constituents: a new hypothesis on the apparent tolerogeneic effect of blood transfusions during transplantation].", "content": "Using the lymphocyte reaction (MLR) as an in vitro model of allogeneic response we have demonstrated that red blood cells (RBC), when phagocytosed by monocytes present in the reaction, induce almost complete suppression of the MLR. A similar effect is achieved by the RBC lysate or purified hemoglobin. These data strongly suggest that the better graft tolerance apparently induced by blood transfusion given to the recipient at the time of transplantation may result from a non specific immunodepressive process induced by the injected erythrocytes, and mediated by the monocyte.", "contents": "[Suppression of the mixed lymphocytic reaction by autologous red cells and their constituents: a new hypothesis on the apparent tolerogeneic effect of blood transfusions during transplantation]. Using the lymphocyte reaction (MLR) as an in vitro model of allogeneic response we have demonstrated that red blood cells (RBC), when phagocytosed by monocytes present in the reaction, induce almost complete suppression of the MLR. A similar effect is achieved by the RBC lysate or purified hemoglobin. These data strongly suggest that the better graft tolerance apparently induced by blood transfusion given to the recipient at the time of transplantation may result from a non specific immunodepressive process induced by the injected erythrocytes, and mediated by the monocyte."} {"id": "PMID:153213", "title": "Follicular growth in fetal and prepubertal ovaries of humans and other primates.", "content": "Follicular growth begins in the fetal ovary as soon as the first follicles are formed. Although orderly follicular growth is found in the fetal ovary, many of the early growing follicles show abnormalties. Follicles with irregular granulosa layers, with hypertrophied or with underdeveloped theca layers, are characteristic. Such follicles are rarely seen after birth. The ovary during childhood is an active organ in which follicular growth and follicular atresia normally take place. Follicles begin to grow at all ages, differentiate to preantral and antral follicles, but degenerate at various stages of their development before they reach pre-ovulatory sizes. Follicular growth in the fetus and children is dependent on hormones. Fetal gonadotrophins are necessary to ensure normal and sequential follicular growth before birth. During childhood a close correlation between follicle growth, hormone response and hormone production seems to exist. Certain diseases and treatment with cytotoxic agents or radiation to the abdomen influence ovarian development and follicular growth. Chromosome abnormalities, especially Turner's syndrome, trisomy 18 or 21, alter normal ovarian development by reducing the pool of available follicles and inhibiting follicular growth. Treatment with cytotoxic drugs inhibits follicular growth, while abdominal irradiation in childhood unless the ovaries are adequately shielded causes permanent damage by destroying the small follicles.", "contents": "Follicular growth in fetal and prepubertal ovaries of humans and other primates. Follicular growth begins in the fetal ovary as soon as the first follicles are formed. Although orderly follicular growth is found in the fetal ovary, many of the early growing follicles show abnormalties. Follicles with irregular granulosa layers, with hypertrophied or with underdeveloped theca layers, are characteristic. Such follicles are rarely seen after birth. The ovary during childhood is an active organ in which follicular growth and follicular atresia normally take place. Follicles begin to grow at all ages, differentiate to preantral and antral follicles, but degenerate at various stages of their development before they reach pre-ovulatory sizes. Follicular growth in the fetus and children is dependent on hormones. Fetal gonadotrophins are necessary to ensure normal and sequential follicular growth before birth. During childhood a close correlation between follicle growth, hormone response and hormone production seems to exist. Certain diseases and treatment with cytotoxic agents or radiation to the abdomen influence ovarian development and follicular growth. Chromosome abnormalities, especially Turner's syndrome, trisomy 18 or 21, alter normal ovarian development by reducing the pool of available follicles and inhibiting follicular growth. Treatment with cytotoxic drugs inhibits follicular growth, while abdominal irradiation in childhood unless the ovaries are adequately shielded causes permanent damage by destroying the small follicles."} {"id": "PMID:153214", "title": "Dermatoglyphics in parents of children with trisomy 21. Evaluation of their interest in genetic counselling.", "content": "Dermal patterns in a group of Down's syndrome patients, a normal control population and a group of parents of Down's syndrome patients were studied in an attempt to identify an Index Score to be used in differentiating controls from parents of Down's syndrome children. Using only three patterns (simian crease, palmar hypothenar pattern and Cummins' Index), a parents' Index Score was established which correctly diagnosed 80.83% of controls and 79.17% of parents. The predictive value of this index and its interest in genetic counselling are discussed.", "contents": "Dermatoglyphics in parents of children with trisomy 21. Evaluation of their interest in genetic counselling. Dermal patterns in a group of Down's syndrome patients, a normal control population and a group of parents of Down's syndrome patients were studied in an attempt to identify an Index Score to be used in differentiating controls from parents of Down's syndrome children. Using only three patterns (simian crease, palmar hypothenar pattern and Cummins' Index), a parents' Index Score was established which correctly diagnosed 80.83% of controls and 79.17% of parents. The predictive value of this index and its interest in genetic counselling are discussed."} {"id": "PMID:153215", "title": "Surgical treatment of Scheuermann's adult kyphosis: case report.", "content": "A 39-year-old woman with severe Scheuermann's kyphosis complaining of back pain was treated surgically. The following operations were performed in stages to correct a fixed kyphosis: (1) total diskectomy through an anterior approach; (2) application of the halo pelvic distraction apparatus; (3) anterior spine fusion following correction by spinal distraction. She was relieved of her complaints and deformity at a 3 year follow-up examination.", "contents": "Surgical treatment of Scheuermann's adult kyphosis: case report. A 39-year-old woman with severe Scheuermann's kyphosis complaining of back pain was treated surgically. The following operations were performed in stages to correct a fixed kyphosis: (1) total diskectomy through an anterior approach; (2) application of the halo pelvic distraction apparatus; (3) anterior spine fusion following correction by spinal distraction. She was relieved of her complaints and deformity at a 3 year follow-up examination."} {"id": "PMID:153219", "title": "The mechanism for the promotion of tenderness in meat during the post-mortem process: a review.", "content": "The post-mortem changes in the chemical composition and structure of striated muscle have been reviewed on the basis of various concepts that emerged from the studies of different investigators to explain the course of tenderization of meat during aging. These concepts include the changes in the sarcoplasmic proteins, myofibrillar proteins (such as complete dissociation of actomyosin, partial dissociation of actomyosin, cleavage of disulfide linkages, depolymerization of F-actin filaments, cleavage of myosin filaments, disorganization of Z-bands and the troponin-tropomyosin complex), sarcolemma, connective tissue elements (collagen fibrils, ground substance), and the protein-ion relationship of the muscle cells (more strictly, syncytia). The experimental evidence for and against each of the views is discussed critically in the light of certain fundamentals of biophysical chemistry and biochemistry. Finally, an alternative hypothesis has been presented based on the differential effect of the post-mortem formation of lactic acid (H+ ion concentration) on the intra- and extracellular components of muscle and the possible role of lysosomal cathepsins. Consequently, a series of biophysical, biochemical, and ultrastructural changes seem to account for the mechanism by which meat becomes tender during the aging process.", "contents": "The mechanism for the promotion of tenderness in meat during the post-mortem process: a review. The post-mortem changes in the chemical composition and structure of striated muscle have been reviewed on the basis of various concepts that emerged from the studies of different investigators to explain the course of tenderization of meat during aging. These concepts include the changes in the sarcoplasmic proteins, myofibrillar proteins (such as complete dissociation of actomyosin, partial dissociation of actomyosin, cleavage of disulfide linkages, depolymerization of F-actin filaments, cleavage of myosin filaments, disorganization of Z-bands and the troponin-tropomyosin complex), sarcolemma, connective tissue elements (collagen fibrils, ground substance), and the protein-ion relationship of the muscle cells (more strictly, syncytia). The experimental evidence for and against each of the views is discussed critically in the light of certain fundamentals of biophysical chemistry and biochemistry. Finally, an alternative hypothesis has been presented based on the differential effect of the post-mortem formation of lactic acid (H+ ion concentration) on the intra- and extracellular components of muscle and the possible role of lysosomal cathepsins. Consequently, a series of biophysical, biochemical, and ultrastructural changes seem to account for the mechanism by which meat becomes tender during the aging process."} {"id": "PMID:153226", "title": "Enzyme histochemistry of the rat hippocampus during experimental status epilepticus.", "content": "EEG registered hippocampal status epilepticus (HSE) was provoked in 41 adult albino rats by intraseptal injection of ouabain, and the hippocampus was studied from 1 1/2 to 24 hr with the enzyme histochemical tests for succinic dehydrogenase (SDH), lactic dehydrogenase (LDH), thiaminopyrophosphatase (TPPase), acid phosphatase (AcPase), Mg2+ adenosine triphosphatase (Mg2++ ATPase), and with general and neurohistological stains. In a first group of animals (1 1/2 to 10 hr of HSE), a stage of general increase in enzymatic activity was detected in the pyramidal neurons (SDH, LDH, AcPase, and TPPase). Mg2+ ATPase showed a marked increase in astrocytes. In a second group (more than 10 hr of HSE), SDH was found decreased in the dendritic fields. LDH activity persisted in neuronal bodies, and AcPase and TPPase showed diffuse activity in the cytoplasm of some pyramidal neurons. In a third group (more than 18 hr of HSE), SDH activity was low. No AcPase granules were observed in some pyramidal neurons and TPPase was negative in some areas of pyramidal layer. Mg2+ ATPase reaction showed scare and retracted astroglial processes. These changes were coincident with \"cellular ghosts\" observed with hematoxylin-eosin techniques of the same samples in the pyramidal field and were interpreted as cellular death, attributed to relative anoxia following neuronal discharge.", "contents": "Enzyme histochemistry of the rat hippocampus during experimental status epilepticus. EEG registered hippocampal status epilepticus (HSE) was provoked in 41 adult albino rats by intraseptal injection of ouabain, and the hippocampus was studied from 1 1/2 to 24 hr with the enzyme histochemical tests for succinic dehydrogenase (SDH), lactic dehydrogenase (LDH), thiaminopyrophosphatase (TPPase), acid phosphatase (AcPase), Mg2+ adenosine triphosphatase (Mg2++ ATPase), and with general and neurohistological stains. In a first group of animals (1 1/2 to 10 hr of HSE), a stage of general increase in enzymatic activity was detected in the pyramidal neurons (SDH, LDH, AcPase, and TPPase). Mg2+ ATPase showed a marked increase in astrocytes. In a second group (more than 10 hr of HSE), SDH was found decreased in the dendritic fields. LDH activity persisted in neuronal bodies, and AcPase and TPPase showed diffuse activity in the cytoplasm of some pyramidal neurons. In a third group (more than 18 hr of HSE), SDH activity was low. No AcPase granules were observed in some pyramidal neurons and TPPase was negative in some areas of pyramidal layer. Mg2+ ATPase reaction showed scare and retracted astroglial processes. These changes were coincident with \"cellular ghosts\" observed with hematoxylin-eosin techniques of the same samples in the pyramidal field and were interpreted as cellular death, attributed to relative anoxia following neuronal discharge."} {"id": "PMID:153227", "title": "Characterization of (Mg,Ca)-ATPase activity in rat pancreatic plasma membranes.", "content": "1. Pancreatic plasma membranes containing a high adenylate cyclase activity and a low contamination by cytochrome c oxidase were isolated from the rat by sucrose density centrifugation. The preparation contained an (Mg,Ca)-ATPase of high activity with the following characteristics. 2. The ATPase activity was shown to have two apparent Km values for Mg-ATP (0.24 +/- 0.09 mM and 1.15 +/- 0.21 mM) and two apparent Km values for Ca-ATP (0.14 +/- 0.09 mM and 0.68 +/- 0.10 mM). Mg-GTP and Ca-GTP were also hydrolysed by the preparation. The phase transition temperature was 19.3 +/- 1.0 degrees C for the Mg-ATPase and 22.6 +/- 1.1 degrees C for the Ca-ATPase activities. 3. Three lines of evidence suggest that Mg-ATP and Ca-ATP were substrates for the same enzyme: Mg-dependent and Ca-dependent activities were not additive; the two activities showed the same pH optimum at 8.0; and the nonionic detergents Triton X-100, Triton X-305, Triton N-101, Lubrol P 12 A, and digitonin, produced a parallel solubilization of the two activities. 4. Enzyme activities were insensitive to potassium, sodium, ouabain, pancreozymin, carbamoyl-choline, secretin, concanavalin A, wheat germ agglutinin, and soybean lectin.", "contents": "Characterization of (Mg,Ca)-ATPase activity in rat pancreatic plasma membranes. 1. Pancreatic plasma membranes containing a high adenylate cyclase activity and a low contamination by cytochrome c oxidase were isolated from the rat by sucrose density centrifugation. The preparation contained an (Mg,Ca)-ATPase of high activity with the following characteristics. 2. The ATPase activity was shown to have two apparent Km values for Mg-ATP (0.24 +/- 0.09 mM and 1.15 +/- 0.21 mM) and two apparent Km values for Ca-ATP (0.14 +/- 0.09 mM and 0.68 +/- 0.10 mM). Mg-GTP and Ca-GTP were also hydrolysed by the preparation. The phase transition temperature was 19.3 +/- 1.0 degrees C for the Mg-ATPase and 22.6 +/- 1.1 degrees C for the Ca-ATPase activities. 3. Three lines of evidence suggest that Mg-ATP and Ca-ATP were substrates for the same enzyme: Mg-dependent and Ca-dependent activities were not additive; the two activities showed the same pH optimum at 8.0; and the nonionic detergents Triton X-100, Triton X-305, Triton N-101, Lubrol P 12 A, and digitonin, produced a parallel solubilization of the two activities. 4. Enzyme activities were insensitive to potassium, sodium, ouabain, pancreozymin, carbamoyl-choline, secretin, concanavalin A, wheat germ agglutinin, and soybean lectin."} {"id": "PMID:153223", "title": "Diabetes mellitus and autonomic dysfunction after vacor rodenticide ingestion.", "content": "A case of N-3 pyridylmethyl-N' 4 nitrophenyl urea (Vacor) rodenticide poisoning in a 52-year-old man is presented. Vacor is structurally related to alloxan and streptozotocin, agents that have been used extensively to produce diabetes mellitus in laboratory animals. Seven days after ingestion of Vacor, the patient presented in diabetic ketoacidosis complicated by postural hypotension and adynamic ileus. The patient recovered from ketoacidosis but has continued to require insulin. With infusion of arginine, glucagon rose from 185 to 650 pg./ml. and C-peptide from 0.5 to 3.4 ng./ml. Six weeks after onset of diabetes, no anti-islet-cell antibodies were detected. Muscle capillary basement membrane thickness on electron microscopy was found to be 1,918 +/- 194 A. The absence of hyperglycemia after Vacor ingestion should not lead to complacency on the part of the attending physician. The patient must be observed closely for development of ketoacidosis and treated prophylactically with nicotinamide, the suggested antidote.", "contents": "Diabetes mellitus and autonomic dysfunction after vacor rodenticide ingestion. A case of N-3 pyridylmethyl-N' 4 nitrophenyl urea (Vacor) rodenticide poisoning in a 52-year-old man is presented. Vacor is structurally related to alloxan and streptozotocin, agents that have been used extensively to produce diabetes mellitus in laboratory animals. Seven days after ingestion of Vacor, the patient presented in diabetic ketoacidosis complicated by postural hypotension and adynamic ileus. The patient recovered from ketoacidosis but has continued to require insulin. With infusion of arginine, glucagon rose from 185 to 650 pg./ml. and C-peptide from 0.5 to 3.4 ng./ml. Six weeks after onset of diabetes, no anti-islet-cell antibodies were detected. Muscle capillary basement membrane thickness on electron microscopy was found to be 1,918 +/- 194 A. The absence of hyperglycemia after Vacor ingestion should not lead to complacency on the part of the attending physician. The patient must be observed closely for development of ketoacidosis and treated prophylactically with nicotinamide, the suggested antidote."} {"id": "PMID:153229", "title": "Assembly of the mitochondrial membrane system: mutations in the pho2 locus of the mitochondrial genome of Saccharomyces cerevisiae.", "content": "Two mutants of Saccharomyces cerevisiae which show a loss of mitochondrial rutamycin-sensitive ATPase activity are described. Although phenotypically similar to mutants of the mitochondrial locus pho1 [F. Foury and A. Tzagoloff (1976) Eur. J. Biochem. 68, 113-119], these mutants define a second ATPase locus on the mitochondrial DNA (designated pho2), which is genetically unlinked to pho1. Analysis of recombination in crosses involving multiple antibiotic resistance markers indicates that the locus is in the segment of the genome between ery1 and oli2, very close to oli1. In fact it is proposed that the oli1 and pho2 mutations are in the same gene. Supporting evidence for this proposal includes: 1. The analysis of marker retention in petite mutants shows that the oli1 and pho2 loci were either retained or lost together in all cases. 2. Recombination frequencies of 0.05% or less are observed in crosses between the oli1 and pho2 loci. 3. When rho+ revertants are isolated from the pho2 mutants they frequently are oligomycin resistant. 4. pho2 mutants have an altered subunit 9 of the ATPase complex.", "contents": "Assembly of the mitochondrial membrane system: mutations in the pho2 locus of the mitochondrial genome of Saccharomyces cerevisiae. Two mutants of Saccharomyces cerevisiae which show a loss of mitochondrial rutamycin-sensitive ATPase activity are described. Although phenotypically similar to mutants of the mitochondrial locus pho1 [F. Foury and A. Tzagoloff (1976) Eur. J. Biochem. 68, 113-119], these mutants define a second ATPase locus on the mitochondrial DNA (designated pho2), which is genetically unlinked to pho1. Analysis of recombination in crosses involving multiple antibiotic resistance markers indicates that the locus is in the segment of the genome between ery1 and oli2, very close to oli1. In fact it is proposed that the oli1 and pho2 mutations are in the same gene. Supporting evidence for this proposal includes: 1. The analysis of marker retention in petite mutants shows that the oli1 and pho2 loci were either retained or lost together in all cases. 2. Recombination frequencies of 0.05% or less are observed in crosses between the oli1 and pho2 loci. 3. When rho+ revertants are isolated from the pho2 mutants they frequently are oligomycin resistant. 4. pho2 mutants have an altered subunit 9 of the ATPase complex."} {"id": "PMID:153230", "title": "Characterization of the dicyclohexylcarbodiimide-binding protein isolated from chloroplast membranes.", "content": "Characterization of a butanol-solubilized protein isolated from chloroplast membranes is reported. The proteolipid, which specifically and covalently binds dicyclohexylcarbodiimide, has an apparent molecular weight of 8,000 in dodecylsulfate electrophoresis. The minimum molecular weight calculated from amino acid analysis data is 7,700. N-Formyl-methionine was determined to be the N-terminal amino acid. Glycine, alanine and leucine were present in elevated amounts, resulting in a polarity of 29%. Cysteine and histidine were lacking. In high-voltage electrophoresis the peptide appeared as a single homogenous spot which migrated, at pH 6.5, with the relative mobility of glycine. At concentrations where dicyclohexylcarbodiimide inhibited ATPase activity maximally (20 nmol per mg membrane protein), 0.17 nmol dicyclohexylcarbodiimide was covalently bound per nmol isolated proteolipid, indicating that one out of six molecules of proteolipid was labeled.", "contents": "Characterization of the dicyclohexylcarbodiimide-binding protein isolated from chloroplast membranes. Characterization of a butanol-solubilized protein isolated from chloroplast membranes is reported. The proteolipid, which specifically and covalently binds dicyclohexylcarbodiimide, has an apparent molecular weight of 8,000 in dodecylsulfate electrophoresis. The minimum molecular weight calculated from amino acid analysis data is 7,700. N-Formyl-methionine was determined to be the N-terminal amino acid. Glycine, alanine and leucine were present in elevated amounts, resulting in a polarity of 29%. Cysteine and histidine were lacking. In high-voltage electrophoresis the peptide appeared as a single homogenous spot which migrated, at pH 6.5, with the relative mobility of glycine. At concentrations where dicyclohexylcarbodiimide inhibited ATPase activity maximally (20 nmol per mg membrane protein), 0.17 nmol dicyclohexylcarbodiimide was covalently bound per nmol isolated proteolipid, indicating that one out of six molecules of proteolipid was labeled."} {"id": "PMID:153231", "title": "The management of congenital tricuspid incompetence.", "content": "2 examples of severe tricuspid incompetence presenting in the newborn period are described. Both recovered with medical treatment alone, with subsequent decrease in tricuspid incompetence. Postnatal course is attributed to normal decrease in pulmonary vascular resistance. Some infants may be at considerable risk until this decrease occurs.", "contents": "The management of congenital tricuspid incompetence. 2 examples of severe tricuspid incompetence presenting in the newborn period are described. Both recovered with medical treatment alone, with subsequent decrease in tricuspid incompetence. Postnatal course is attributed to normal decrease in pulmonary vascular resistance. Some infants may be at considerable risk until this decrease occurs."} {"id": "PMID:153232", "title": "Rate of drug metabolism in man measured by 14CO2-breath analysis.", "content": "Exhalation of 14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of 14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of 14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of 14C-demethylation breath tests. In particular, they are consistent with the hypothesis that 14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.", "contents": "Rate of drug metabolism in man measured by 14CO2-breath analysis. Exhalation of 14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of 14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of 14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of 14C-demethylation breath tests. In particular, they are consistent with the hypothesis that 14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation."} {"id": "PMID:153235", "title": "Intrinsic fluorescence of mitochondrial F1-ATPase.", "content": "The emission maximum of the fluorescence spectrum of mitochondrial F1-ATPase is shifted from 305 to 334 nm when the excitation wavelength is altered from 270 to 300 nm. This indicates that both tyrosine and tryptophan contribute to the intrinsic fluorescence of the F1-ATPase.", "contents": "Intrinsic fluorescence of mitochondrial F1-ATPase. The emission maximum of the fluorescence spectrum of mitochondrial F1-ATPase is shifted from 305 to 334 nm when the excitation wavelength is altered from 270 to 300 nm. This indicates that both tyrosine and tryptophan contribute to the intrinsic fluorescence of the F1-ATPase."} {"id": "PMID:153236", "title": "The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia.", "content": "I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine.", "contents": "The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia. I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine."} {"id": "PMID:153243", "title": "Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea.", "content": "The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen.", "contents": "Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea. The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen."} {"id": "PMID:153244", "title": "[Receptor adaptation of muscle spindles treated in different ways].", "content": "Comparison of the grades of 60 sensitive muscle spindle terminals on two actions: gradual stretch of the muscle and short intensive tetanization of the muscle nerve, showed that, irrespective of the mode of action, the character of adaptation remains the smae in majority of units. The speed of receptors adaptation depends not on the specific of testing precedures, but, apparently, on the means of connection of the sensitive terminals with different types of intrafusal muscle fibers with different elasticviscous properties. The possible reason for speedy adaptation of muscle receptors of elementary dynamic type, is discussed.", "contents": "[Receptor adaptation of muscle spindles treated in different ways]. Comparison of the grades of 60 sensitive muscle spindle terminals on two actions: gradual stretch of the muscle and short intensive tetanization of the muscle nerve, showed that, irrespective of the mode of action, the character of adaptation remains the smae in majority of units. The speed of receptors adaptation depends not on the specific of testing precedures, but, apparently, on the means of connection of the sensitive terminals with different types of intrafusal muscle fibers with different elasticviscous properties. The possible reason for speedy adaptation of muscle receptors of elementary dynamic type, is discussed."} {"id": "PMID:153245", "title": "[Interrelationship between contact coagulation, surface charge and roughness].", "content": "The negative surface charge and the mechanically even surface were found in vitro to hinder the blood hypercoagulation, fibrin absorption, and thrombocytes hyperadhesion. The surface negative electrical charge of 6--10(-9)Cl/cm2 and the surface of the 9--14th class of mechanical evenness seem to be optimal for prophylaxis of thrombosis at the blood-surface border. The surface negative electrical charge reduces the possibility of thrombosis on mechanically rough surface.", "contents": "[Interrelationship between contact coagulation, surface charge and roughness]. The negative surface charge and the mechanically even surface were found in vitro to hinder the blood hypercoagulation, fibrin absorption, and thrombocytes hyperadhesion. The surface negative electrical charge of 6--10(-9)Cl/cm2 and the surface of the 9--14th class of mechanical evenness seem to be optimal for prophylaxis of thrombosis at the blood-surface border. The surface negative electrical charge reduces the possibility of thrombosis on mechanically rough surface."} {"id": "PMID:153246", "title": "Immunologic study of T and B lymphocytes in thymectomized monkeys after irradiation and autologous bone marrow transplantation.", "content": "Rhesus monkeys were exposed to total-body gamma-irradiation (60Co) with 700R following adult thymectomy, and then protected with autologous bone marrow. Transplantation immunity in TxIBM animals was impaired: skin allografts survived for 19 to 38 days. The percentage of T and B lymphocytes studied by the rosette technique and immunofluorescent staining for Ig did not substantially change when examined in early as well as late periods after TxIBM. Functional capacities of lymphocytes were measured in vitro by stimulation with phytohaemagglutinin and with allogeneic cells in mixed lymphocyte cultures. MLC reactivity in TxIBM monkeys did not recover in the early and later periods following treatment. PHA responsiveness was retained in both these periods. These findings together with the results obtained in the analysis of unstable chromosomal aberrations suggested that PHA-responsive and MLC-reactive cell subpopulations of monkey blood lymphocytes differed in the degree of thymus dependence.", "contents": "Immunologic study of T and B lymphocytes in thymectomized monkeys after irradiation and autologous bone marrow transplantation. Rhesus monkeys were exposed to total-body gamma-irradiation (60Co) with 700R following adult thymectomy, and then protected with autologous bone marrow. Transplantation immunity in TxIBM animals was impaired: skin allografts survived for 19 to 38 days. The percentage of T and B lymphocytes studied by the rosette technique and immunofluorescent staining for Ig did not substantially change when examined in early as well as late periods after TxIBM. Functional capacities of lymphocytes were measured in vitro by stimulation with phytohaemagglutinin and with allogeneic cells in mixed lymphocyte cultures. MLC reactivity in TxIBM monkeys did not recover in the early and later periods following treatment. PHA responsiveness was retained in both these periods. These findings together with the results obtained in the analysis of unstable chromosomal aberrations suggested that PHA-responsive and MLC-reactive cell subpopulations of monkey blood lymphocytes differed in the degree of thymus dependence."} {"id": "PMID:153251", "title": "Studies of cultured human fibroblasts in diabetes mellitus: changes in heparan sulfate.", "content": "The incorporation of [35S]sulfate into glycosaminoglycans was studied in cultures of normal and diabetic skin fibroblasts. Heparan sulfate was determined by column chromatography after enzymatic degradation of chondroitin sulfates and dermatan sulfate by chondroitinase ABE. Cultured skin fibroblasts from both insulin-dependent and noninsulin-dependent diabetics were found to have increased proportions of heparan sulfate in the media relative to the other sulfated glycosaminoglycans.", "contents": "Studies of cultured human fibroblasts in diabetes mellitus: changes in heparan sulfate. The incorporation of [35S]sulfate into glycosaminoglycans was studied in cultures of normal and diabetic skin fibroblasts. Heparan sulfate was determined by column chromatography after enzymatic degradation of chondroitin sulfates and dermatan sulfate by chondroitinase ABE. Cultured skin fibroblasts from both insulin-dependent and noninsulin-dependent diabetics were found to have increased proportions of heparan sulfate in the media relative to the other sulfated glycosaminoglycans."} {"id": "PMID:153264", "title": "[Measurement and differential demonstration of renal blood flow by computer angiography (author's transl)].", "content": "A new computer-aided x-ray technique is presented which, unlike conventional cine- or video-densitometry, allows a high-resolution quantitative display of the parameters of renal blood flow as so-called 'functional images'. The parameters include blood flow velocity and local perfusion of the kidney. This technique, which we call computer angiography, has decisive advantages; the functional images provide more, and more rapid, information on renal blood flow dynamics than can be obtained by the qualitative evaluation of a series of pictures. The clinical relevance of computer angiography is illustrated by a nephrotic syndrome, polycystic disease and a hypernephroma.", "contents": "[Measurement and differential demonstration of renal blood flow by computer angiography (author's transl)]. A new computer-aided x-ray technique is presented which, unlike conventional cine- or video-densitometry, allows a high-resolution quantitative display of the parameters of renal blood flow as so-called 'functional images'. The parameters include blood flow velocity and local perfusion of the kidney. This technique, which we call computer angiography, has decisive advantages; the functional images provide more, and more rapid, information on renal blood flow dynamics than can be obtained by the qualitative evaluation of a series of pictures. The clinical relevance of computer angiography is illustrated by a nephrotic syndrome, polycystic disease and a hypernephroma."} {"id": "PMID:153265", "title": "[Phantom measurements of spatial resolution and the partial-volume-effect in computer tomography (author's transl)].", "content": "The present work deals with the problem of demonstrating tissue changes of small volume by computer tomography. Measurements were carried out with the Somatom computer tomograph and evaluated by the Evaluscope (both Siemens); fourteen test situations were devised, using plexiglass rods of varying diameter and different penetration into the level being sectioned. Quantitative relationships were found concerning the spatial resolution for objects of varying sizes, concerning the partial volume effect and the thickness of the section for objects of varying size, and concerning the relationship between resolution and partial volume effect for small objects.", "contents": "[Phantom measurements of spatial resolution and the partial-volume-effect in computer tomography (author's transl)]. The present work deals with the problem of demonstrating tissue changes of small volume by computer tomography. Measurements were carried out with the Somatom computer tomograph and evaluated by the Evaluscope (both Siemens); fourteen test situations were devised, using plexiglass rods of varying diameter and different penetration into the level being sectioned. Quantitative relationships were found concerning the spatial resolution for objects of varying sizes, concerning the partial volume effect and the thickness of the section for objects of varying size, and concerning the relationship between resolution and partial volume effect for small objects."} {"id": "PMID:153266", "title": "[The value of various radiological procedures for the investigation of functional disturbances of renal transplants (author's transl)].", "content": "The value of various radiological examinations was analysed with reference to 75 renal transplants which had developed complications. If the renal poles are marked with metallic clips, the size of the transplant can be estimated by abdominal x-rays. Abnormal size was found exclusively in severe rejection reactions, but only about 50% of acute rejections showed such a change. Contrast examinations were found to be valuable in the diagnosis or exclusion of anatomically localised lesions such as obstructions or anastomotic leaks. They were unsatisfactory in the diagnosis and differential diagnosis of diffuse parenchymatous abnormalities such as rejection or damage during storage.", "contents": "[The value of various radiological procedures for the investigation of functional disturbances of renal transplants (author's transl)]. The value of various radiological examinations was analysed with reference to 75 renal transplants which had developed complications. If the renal poles are marked with metallic clips, the size of the transplant can be estimated by abdominal x-rays. Abnormal size was found exclusively in severe rejection reactions, but only about 50% of acute rejections showed such a change. Contrast examinations were found to be valuable in the diagnosis or exclusion of anatomically localised lesions such as obstructions or anastomotic leaks. They were unsatisfactory in the diagnosis and differential diagnosis of diffuse parenchymatous abnormalities such as rejection or damage during storage."} {"id": "PMID:153267", "title": "[Sonography and phlebography in the investigation of the suprarenals (author's transl)].", "content": "Twelve patients were examined by sonography and phlebography; of these, ten had suprarenal tumours and two suprarenal hyperplasia. The value of sonography and its place compared with radiological examinations is discussed. Sonography is an informative method of screening and should be employed whenever there is clinical suspicion of enlargement of the suprarenals before other radiological methods are used.", "contents": "[Sonography and phlebography in the investigation of the suprarenals (author's transl)]. Twelve patients were examined by sonography and phlebography; of these, ten had suprarenal tumours and two suprarenal hyperplasia. The value of sonography and its place compared with radiological examinations is discussed. Sonography is an informative method of screening and should be employed whenever there is clinical suspicion of enlargement of the suprarenals before other radiological methods are used."} {"id": "PMID:153263", "title": "Experimental evaluation of rigor mortis. I. Histochemical analysis of rat skeletal muscle in the early post-mortem period.", "content": "Histochemical investigation of rat skeletal muscle samples removed immediately post mortem from exercised rats gave the following results: (1) Of the oxidoreductase enzymes studied, there was a slight increase in the activity of cytochrome oxidase. (2) There was no change in the acid- and alkali-stable actomyosin ATPase activity. (3) There was a notable decrease in glycogen concentration. In the case of strychnine intoxication: (1) There was no change in oxidoreductase enzymes. (2) There was an increase in the activity of alkali-stable ATPase in white fibres. (3) The glycogen concentration notably decreased. There was no change in the activity of enzymes studied in those animals sacrificed by anoxia.", "contents": "Experimental evaluation of rigor mortis. I. Histochemical analysis of rat skeletal muscle in the early post-mortem period. Histochemical investigation of rat skeletal muscle samples removed immediately post mortem from exercised rats gave the following results: (1) Of the oxidoreductase enzymes studied, there was a slight increase in the activity of cytochrome oxidase. (2) There was no change in the acid- and alkali-stable actomyosin ATPase activity. (3) There was a notable decrease in glycogen concentration. In the case of strychnine intoxication: (1) There was no change in oxidoreductase enzymes. (2) There was an increase in the activity of alkali-stable ATPase in white fibres. (3) The glycogen concentration notably decreased. There was no change in the activity of enzymes studied in those animals sacrificed by anoxia."} {"id": "PMID:153268", "title": "[The transumbilical occlusionphlebography of the pancreas, the attempt of a new technique (author's transl)].", "content": "The value of selective and superselective arteriography is limited. The difficulties in differentiation between tumors and chronic pancreatitis make it frequently impossible to come to an early diagnosis by the method. Beside arterial vessel changes pathological venous lesions may play a role in view of resectability. Because of anatomical structures phlebography of the vena portae and its origens is not commonly used. Especially selective pancreas phlebography is possible only by means of indirect catherterization. Among the different techniques the transumbilical route seems to be mort effective than recently thought of. In this paper a new technique of pancreas phlebography by means of catheterization of the umbilical vein is introduced. Twelve pr\u00e4parations of human pancreas at autopsy and six postmortal catheterizations of the portal veins in situ in man have been studied. First results of this occlusion-phlebography of the pancreas are presented for the first time. Problems are discussed which may arise when applicating this method in vivo. In is expected to get more important angiographic information about pancreatic diseases. Certainly it can be used to investigate hemodynamic and biochemical changes.", "contents": "[The transumbilical occlusionphlebography of the pancreas, the attempt of a new technique (author's transl)]. The value of selective and superselective arteriography is limited. The difficulties in differentiation between tumors and chronic pancreatitis make it frequently impossible to come to an early diagnosis by the method. Beside arterial vessel changes pathological venous lesions may play a role in view of resectability. Because of anatomical structures phlebography of the vena portae and its origens is not commonly used. Especially selective pancreas phlebography is possible only by means of indirect catherterization. Among the different techniques the transumbilical route seems to be mort effective than recently thought of. In this paper a new technique of pancreas phlebography by means of catheterization of the umbilical vein is introduced. Twelve pr\u00e4parations of human pancreas at autopsy and six postmortal catheterizations of the portal veins in situ in man have been studied. First results of this occlusion-phlebography of the pancreas are presented for the first time. Problems are discussed which may arise when applicating this method in vivo. In is expected to get more important angiographic information about pancreatic diseases. Certainly it can be used to investigate hemodynamic and biochemical changes."} {"id": "PMID:153269", "title": "[Occlusion of the three unpaired aortic branches with the development of an extensive Riolan's anastomosis (author's transl)].", "content": "A 60-year-old patient with occlusion of the inferior and superior mesenteric arteries and the coeliac axis developed a collateral circulation from the iliac arteries through the rectal vessels, the ascending ramus of the inferior mesenteric artery and the medical colic branch of the superior mesenteric artery. These collaterals were able to ensure survival of all three vascular territories. Along the medial wall of the descending colon and the sigmoid a second, less well developed collateral circulation could be demonstrated by iliac arteriography. The branches of the superior mesenteric artery and of the coeliac axis were only partly demonstrated, or failed to fill, during a free aortic injection and a counter current arteriogram. Clinically the occlusion of the unpaired aortic branches manifested itself as periumbilical pain after food. The involvement of the visceral aortic branches to this extent in the presence of generalised vascular disease is related to an attack of dysentry 38 years previously.", "contents": "[Occlusion of the three unpaired aortic branches with the development of an extensive Riolan's anastomosis (author's transl)]. A 60-year-old patient with occlusion of the inferior and superior mesenteric arteries and the coeliac axis developed a collateral circulation from the iliac arteries through the rectal vessels, the ascending ramus of the inferior mesenteric artery and the medical colic branch of the superior mesenteric artery. These collaterals were able to ensure survival of all three vascular territories. Along the medial wall of the descending colon and the sigmoid a second, less well developed collateral circulation could be demonstrated by iliac arteriography. The branches of the superior mesenteric artery and of the coeliac axis were only partly demonstrated, or failed to fill, during a free aortic injection and a counter current arteriogram. Clinically the occlusion of the unpaired aortic branches manifested itself as periumbilical pain after food. The involvement of the visceral aortic branches to this extent in the presence of generalised vascular disease is related to an attack of dysentry 38 years previously."} {"id": "PMID:153270", "title": "[Roentgendiagnostic of the peritoneovenous drainage after Le Veen for ascitestreatment (author's transl)].", "content": "The peritoneovenous drainage after Le Veen offers a possibility of the ascitestreatment. The roentgenexamination showed wrong positions of the katheter as the most frequent cause of dysfunctions. They were regularly combined with venous obstructions. The intraoperativ x-ray diagnostic can fascilate the shunt application and may help to spare a second operation.", "contents": "[Roentgendiagnostic of the peritoneovenous drainage after Le Veen for ascitestreatment (author's transl)]. The peritoneovenous drainage after Le Veen offers a possibility of the ascitestreatment. The roentgenexamination showed wrong positions of the katheter as the most frequent cause of dysfunctions. They were regularly combined with venous obstructions. The intraoperativ x-ray diagnostic can fascilate the shunt application and may help to spare a second operation."} {"id": "PMID:153271", "title": "[Intramural perforation of the oesophagus (author's transl)].", "content": "The authors have seen four patients with perforation into the wall of the oesophagus and have reviewed 17 others described in the literature. They discuss the appearances, causes, symptoms and radiological characteristics of this condition and also deal with its treatment. It is important to differentiate the clinical picture of this type of perforation from cardiac infarcts, aortic dissection and also from transmural perforation, since the treatment varies widely.", "contents": "[Intramural perforation of the oesophagus (author's transl)]. The authors have seen four patients with perforation into the wall of the oesophagus and have reviewed 17 others described in the literature. They discuss the appearances, causes, symptoms and radiological characteristics of this condition and also deal with its treatment. It is important to differentiate the clinical picture of this type of perforation from cardiac infarcts, aortic dissection and also from transmural perforation, since the treatment varies widely."} {"id": "PMID:153272", "title": "[Investigation of the small bowel using an intubation method (author's transl)].", "content": "Small bowel contrast examinations by an intubation method were carried out in our hundred patients suspected of having small bowel disease. The method described by Sellink was used and the time and expenditure for carrying out the procedure was monitored. The effect of changes in the method on side effects and quality of the results were observed. Although the technique requires rather more time and effort, the side effects are minimal once it has been properly worked out and there are definite diagnostic gains compared with conventional methods of investigating the small bowel. The increased information available justifies the use of the intubation technique not only for selected problems, but as the primary method of examination of the small bowel.", "contents": "[Investigation of the small bowel using an intubation method (author's transl)]. Small bowel contrast examinations by an intubation method were carried out in our hundred patients suspected of having small bowel disease. The method described by Sellink was used and the time and expenditure for carrying out the procedure was monitored. The effect of changes in the method on side effects and quality of the results were observed. Although the technique requires rather more time and effort, the side effects are minimal once it has been properly worked out and there are definite diagnostic gains compared with conventional methods of investigating the small bowel. The increased information available justifies the use of the intubation technique not only for selected problems, but as the primary method of examination of the small bowel."} {"id": "PMID:153273", "title": "[The value of abdominal radiographs in the diagnosis of bromurea intoxication (author's transl)].", "content": "Brom-substituted mono-urea hypnotics, which may be taken with suicidal intent, can be demonstrated radiologically. The value of routine abdominal x-rays in the recognition of intoxications has been examined at the University Clinic, Ulm, on patients admitted in 1976 and 1977. It has been shown that it is usually possible radiographically to indicate whether bromurea compounds have been taken in significant quantities, The bromurea has low solubility in the stomach and it is therefore possible to demonstrate the amount and type of substance present; this has some bearing on immediate treatment. Rapid removal of the toxic substance is so important for effective treatment that routine abdominal radiographs appear indicated for all life-threatening intoxications. Confusion with other opaque substances in practise is confined to preparations containing bismuth; although these are widely used, they have no significant toxicity.", "contents": "[The value of abdominal radiographs in the diagnosis of bromurea intoxication (author's transl)]. Brom-substituted mono-urea hypnotics, which may be taken with suicidal intent, can be demonstrated radiologically. The value of routine abdominal x-rays in the recognition of intoxications has been examined at the University Clinic, Ulm, on patients admitted in 1976 and 1977. It has been shown that it is usually possible radiographically to indicate whether bromurea compounds have been taken in significant quantities, The bromurea has low solubility in the stomach and it is therefore possible to demonstrate the amount and type of substance present; this has some bearing on immediate treatment. Rapid removal of the toxic substance is so important for effective treatment that routine abdominal radiographs appear indicated for all life-threatening intoxications. Confusion with other opaque substances in practise is confined to preparations containing bismuth; although these are widely used, they have no significant toxicity."} {"id": "PMID:153274", "title": "[Computer tomography of the mediastinum (author's transl)].", "content": "The scope and limitaitons of computer tomography in the diagnosis of diseases of the mediastinum were studied, using a 20 seconds scanner (EMI CT 5005/12). The mediastinal structures can be accurately differentiated and diagnosis is therefore frequently facilitated. In addition to a knowledge of the anatomy, it is important to be familiar with various types of artefact since these may change the degree of attenuation. Additional use of contrast medium is frequently required.", "contents": "[Computer tomography of the mediastinum (author's transl)]. The scope and limitaitons of computer tomography in the diagnosis of diseases of the mediastinum were studied, using a 20 seconds scanner (EMI CT 5005/12). The mediastinal structures can be accurately differentiated and diagnosis is therefore frequently facilitated. In addition to a knowledge of the anatomy, it is important to be familiar with various types of artefact since these may change the degree of attenuation. Additional use of contrast medium is frequently required."} {"id": "PMID:153275", "title": "[Computer cardio-tomography for tumours of the left atrium (author's transl)].", "content": "The role of computer tomography in the diagnosis of cardiac tumours was demonstrated by three patients with myxomas of the left atrium. After intravenous contrast administration these tumours appeared as relatively translucent space-occupying lesions on the computer tomograph. The invasive method of angio-cardiography is unlikely to provide any additional information concerning tumour size or localisation when compared with non-invasive computer tomography or echo cardiography.", "contents": "[Computer cardio-tomography for tumours of the left atrium (author's transl)]. The role of computer tomography in the diagnosis of cardiac tumours was demonstrated by three patients with myxomas of the left atrium. After intravenous contrast administration these tumours appeared as relatively translucent space-occupying lesions on the computer tomograph. The invasive method of angio-cardiography is unlikely to provide any additional information concerning tumour size or localisation when compared with non-invasive computer tomography or echo cardiography."} {"id": "PMID:153276", "title": "[The radiographic appearances following correction of left-to-right shunts (author's transl)].", "content": "Amongst 22 patients with corrected left-to-right shunts, a diminution in heart size and reduction in central pulmonary arteries and pulmonary plethora was found in about half the patients. A good operative result can be expected, particularly in younger patients with less severe lesions, where the vessels had not been subjected to a high pressure for a long period. The failure of vessels to return to normal is assurmed to be due to changes in the vessel walls. Possible causes for persistent cardiomegaly are, in addition to persistent shunts, coronary artery disease, obesity, inadequate digitalisation and aortic and mitral insufficiency.", "contents": "[The radiographic appearances following correction of left-to-right shunts (author's transl)]. Amongst 22 patients with corrected left-to-right shunts, a diminution in heart size and reduction in central pulmonary arteries and pulmonary plethora was found in about half the patients. A good operative result can be expected, particularly in younger patients with less severe lesions, where the vessels had not been subjected to a high pressure for a long period. The failure of vessels to return to normal is assurmed to be due to changes in the vessel walls. Possible causes for persistent cardiomegaly are, in addition to persistent shunts, coronary artery disease, obesity, inadequate digitalisation and aortic and mitral insufficiency."} {"id": "PMID:153277", "title": "[The assessment of activity of tuberculous lesions. A radiological problem (author's transl)].", "content": "The evaluation of activity of tuberculous lesions in patients with unknown previous course make an additional tomographic assessment of the lesion necessary. The value of this approach is being illustrated by 8 cases.", "contents": "[The assessment of activity of tuberculous lesions. A radiological problem (author's transl)]. The evaluation of activity of tuberculous lesions in patients with unknown previous course make an additional tomographic assessment of the lesion necessary. The value of this approach is being illustrated by 8 cases."} {"id": "PMID:153278", "title": "[Changes in the pulmonary vessels during asthma in childhood (author's transl)].", "content": "One hundred and twenty-eight erect radiographs of the thorax in 42 children with bronchial asthma have been analysed. The criterium for inclusion in this study was the demonstration on once occasion at least of hyperinflation of the lung with a low diaphragm, increased size of lung, narrow heart and increase in the retrosternal transparent area. In all patients there was narrowing of the vessels. In addition, the vessels appeared irregular and curved. Other characteristic radiological findings were tram-lines, obstructed bronchi, peribronchial infiltrates and atelectases. Increasing severity of the attack lead to increasing finding of other radiological changes in the thorax, but these have not yet been statistically examined.", "contents": "[Changes in the pulmonary vessels during asthma in childhood (author's transl)]. One hundred and twenty-eight erect radiographs of the thorax in 42 children with bronchial asthma have been analysed. The criterium for inclusion in this study was the demonstration on once occasion at least of hyperinflation of the lung with a low diaphragm, increased size of lung, narrow heart and increase in the retrosternal transparent area. In all patients there was narrowing of the vessels. In addition, the vessels appeared irregular and curved. Other characteristic radiological findings were tram-lines, obstructed bronchi, peribronchial infiltrates and atelectases. Increasing severity of the attack lead to increasing finding of other radiological changes in the thorax, but these have not yet been statistically examined."} {"id": "PMID:153279", "title": "[Plain film findings in the skull in neurofibromatosis (author's transl)].", "content": "The radiologically demonstrable changes in the skull, which occur in neurofibromatosis, are described. The mesodermal dysplastic changes in the sphenoid and the facial skeleton are diagnostic. Changes secondary to blastomatous processes are not always a consequence of the presence of a tumour; they may result from developmental abnormalities or dural protrusion. In addition one may encounter a series of changes which are not in themselves diagnostic. Problems in the diagnoses and the differential diagnosis are discussed.", "contents": "[Plain film findings in the skull in neurofibromatosis (author's transl)]. The radiologically demonstrable changes in the skull, which occur in neurofibromatosis, are described. The mesodermal dysplastic changes in the sphenoid and the facial skeleton are diagnostic. Changes secondary to blastomatous processes are not always a consequence of the presence of a tumour; they may result from developmental abnormalities or dural protrusion. In addition one may encounter a series of changes which are not in themselves diagnostic. Problems in the diagnoses and the differential diagnosis are discussed."} {"id": "PMID:153280", "title": "[Double contours and companion shadows in the skull associated with anaemias (author's transl)].", "content": "Lateral X-ray pictures of the skull in certain several and chronic disorders of the blood as thalassaemia, congenital haemolytic anaemia, sickle cell anaemia and iron deficiency disease show frequently changes of the outlines of the cranial bones. They consist of a double contour of the outer cranial border and on the interior side below the sagittal sutura of a band-like shadow or of multiple stripes and lines running parallel to the carnial vault. They concern the parietal bones and may extend from the bregma till to the lamda or occupy only a part of this distance. The roentgenological features are due to the enlargement of the crainal bones, the bulging out of both parietal bondes, the sometimes enlarged and deepened borders of the sulcus sagittalis superior and particularly to the furrow and depression on the skull above the sagittal suture caused by the protruding parietal bones on both sides. As these different abnormal structures must be passed by the picturing X-ray, effects of superposition and interference are produced. Longitudinal ridges or bony edges which could explain the roentgenological findings could not be established. Since the peculiar alterations of the cranial bones are mainly found in the mentioned blood disorders, where they are caused by the overgrowing red marrow, they also display the same roentgenological features. These features are, therefore, a characteristic sign of these diseases.", "contents": "[Double contours and companion shadows in the skull associated with anaemias (author's transl)]. Lateral X-ray pictures of the skull in certain several and chronic disorders of the blood as thalassaemia, congenital haemolytic anaemia, sickle cell anaemia and iron deficiency disease show frequently changes of the outlines of the cranial bones. They consist of a double contour of the outer cranial border and on the interior side below the sagittal sutura of a band-like shadow or of multiple stripes and lines running parallel to the carnial vault. They concern the parietal bones and may extend from the bregma till to the lamda or occupy only a part of this distance. The roentgenological features are due to the enlargement of the crainal bones, the bulging out of both parietal bondes, the sometimes enlarged and deepened borders of the sulcus sagittalis superior and particularly to the furrow and depression on the skull above the sagittal suture caused by the protruding parietal bones on both sides. As these different abnormal structures must be passed by the picturing X-ray, effects of superposition and interference are produced. Longitudinal ridges or bony edges which could explain the roentgenological findings could not be established. Since the peculiar alterations of the cranial bones are mainly found in the mentioned blood disorders, where they are caused by the overgrowing red marrow, they also display the same roentgenological features. These features are, therefore, a characteristic sign of these diseases."} {"id": "PMID:153281", "title": "[Physiological increase in the mineral content of the radius and ulna during growth (author's transl)].", "content": "Bone mineral estimations were carried out in 273 normal youngsters aged 6 to 18 years using a 125I photon absorption technique. Measurements were carried out at two points on the radius and ulna. Normal values for different ages were calculated for both sexes. Statistical analysis of the data, together with measurements obtained from 773 adults, has shown that the curve derived from children and adolescents merges smoothly with that for adults.", "contents": "[Physiological increase in the mineral content of the radius and ulna during growth (author's transl)]. Bone mineral estimations were carried out in 273 normal youngsters aged 6 to 18 years using a 125I photon absorption technique. Measurements were carried out at two points on the radius and ulna. Normal values for different ages were calculated for both sexes. Statistical analysis of the data, together with measurements obtained from 773 adults, has shown that the curve derived from children and adolescents merges smoothly with that for adults."} {"id": "PMID:153282", "title": "[The place of radiology in tuberous sclerosis (author's transl)].", "content": "Tuberous sclerosis is a rare disease in which hamartomas may be found in the brain, the retina, the skin and in other internal organs. The classic form of the disease showing mental retardation, epilepsy and adenoma sebaceum is easily recognised. Incomplete forms, however, can provide considerable diagnostic difficulties. Angiographically, appearances are found which cannot be differentiated with certainty from those of malignant tumours. Malignant tumours are very rare in this condition. Nephrectomy can be avoided if the diagnosis is made at an early stage. Two female patients are reported, in one of whom the diagnosis was made by renal angiography. Despite the presence of large tumours in both kidneys, these organs could be preserved by surgery. In the second patient there were also bilateral renal hamartomas, but surgery was not carried out. Both cases showed typical changes in the fingers and toes as well as intracerebral calcification, and in one the lungs were affected.", "contents": "[The place of radiology in tuberous sclerosis (author's transl)]. Tuberous sclerosis is a rare disease in which hamartomas may be found in the brain, the retina, the skin and in other internal organs. The classic form of the disease showing mental retardation, epilepsy and adenoma sebaceum is easily recognised. Incomplete forms, however, can provide considerable diagnostic difficulties. Angiographically, appearances are found which cannot be differentiated with certainty from those of malignant tumours. Malignant tumours are very rare in this condition. Nephrectomy can be avoided if the diagnosis is made at an early stage. Two female patients are reported, in one of whom the diagnosis was made by renal angiography. Despite the presence of large tumours in both kidneys, these organs could be preserved by surgery. In the second patient there were also bilateral renal hamartomas, but surgery was not carried out. Both cases showed typical changes in the fingers and toes as well as intracerebral calcification, and in one the lungs were affected."} {"id": "PMID:153283", "title": "[Lymphography for the prognosis of carcinoma of the cervix (author's transl)].", "content": "Ninety-two patients with carcinoma of the cervix, who had lymphograms before treatment, were observed for a period of three to five years. In patients with lymph node metastases 57.1% were found to have recurrences or metastases, or died during that period. Amongst patients with normal lymphograms the corresponding figure was 11.3%. These findings were true for each stage of the disease. Follow-up studies with histological examination of the lymph nodes have shown that the prognosis of carcinoma of the cervix is totally different if lymph node metastases are present. Separation into cases with good and bad prognosis can be achieved by pre-treatment lymphography. The radiological findings concerning lymph nodes should therefore be included in the classification of carcinoma of the cervix; the T.N.M. calssification of U.I.C.C. makes this possible.", "contents": "[Lymphography for the prognosis of carcinoma of the cervix (author's transl)]. Ninety-two patients with carcinoma of the cervix, who had lymphograms before treatment, were observed for a period of three to five years. In patients with lymph node metastases 57.1% were found to have recurrences or metastases, or died during that period. Amongst patients with normal lymphograms the corresponding figure was 11.3%. These findings were true for each stage of the disease. Follow-up studies with histological examination of the lymph nodes have shown that the prognosis of carcinoma of the cervix is totally different if lymph node metastases are present. Separation into cases with good and bad prognosis can be achieved by pre-treatment lymphography. The radiological findings concerning lymph nodes should therefore be included in the classification of carcinoma of the cervix; the T.N.M. calssification of U.I.C.C. makes this possible."} {"id": "PMID:153284", "title": "[Chromosomal changes following irradiation with small doses (author's transl)].", "content": "The authors examined the chromosomes of 20 patients who underwent thyroid investigations. Leucocyte cultures from peripheral blood were studied immediately before the indtroduction of 131I, and again after 48 hours. The results indicate that a total body dose of 0.05 rad increases chromatid damage as well as increasing the incidence of labile chromosome changes.", "contents": "[Chromosomal changes following irradiation with small doses (author's transl)]. The authors examined the chromosomes of 20 patients who underwent thyroid investigations. Leucocyte cultures from peripheral blood were studied immediately before the indtroduction of 131I, and again after 48 hours. The results indicate that a total body dose of 0.05 rad increases chromatid damage as well as increasing the incidence of labile chromosome changes."} {"id": "PMID:153293", "title": "[Panel discussion: problems of the specialist's duty to inform the patient (author's transl)].", "content": "The obligation of the physician to inform the patient--which he has to prove in case of a suit--is based on the patient's right of selfdetermination. This self-decision information was subject of the panel discussion. Not discussed in detail were the information concerning diagnosis and prognosis, and the instruction of the patient regarding his conduct postoperatively and during medical treatment. Not considered was the so-called malpractice and negligence respectively. Medical liability suits are increasing for various reasons and are frequently directed at a failure to inform the patient because the patient is often unable to prove a negligence of the physician (\"surrogate liability\"). The dimension of the duty of disclosure (complete information--no information at all) is discussed in general and with special regard to the radiological field.", "contents": "[Panel discussion: problems of the specialist's duty to inform the patient (author's transl)]. The obligation of the physician to inform the patient--which he has to prove in case of a suit--is based on the patient's right of selfdetermination. This self-decision information was subject of the panel discussion. Not discussed in detail were the information concerning diagnosis and prognosis, and the instruction of the patient regarding his conduct postoperatively and during medical treatment. Not considered was the so-called malpractice and negligence respectively. Medical liability suits are increasing for various reasons and are frequently directed at a failure to inform the patient because the patient is often unable to prove a negligence of the physician (\"surrogate liability\"). The dimension of the duty of disclosure (complete information--no information at all) is discussed in general and with special regard to the radiological field."} {"id": "PMID:153294", "title": "[Thermographic investigations of thyroid foci (author's transl)].", "content": "Thyroid foci showing uptake on scintigraphy were examined by thermography and compared with foci showing no uptake. The following results were obtained: 1. One fifth of scintigraphically \"cold\" foci were also cold on the thermogram. 2. Two thirds to four fifths of foci showing scintigraphic uptake appeared as warm spots on the thermogram. 3. 10% of foci showing no uptake appeared as thermographic circumscribed hot spots. The combination of findings in \"3\" is suspicious of malignancy and this justifies the use of thermography in addition to scintigraphy and cytology.", "contents": "[Thermographic investigations of thyroid foci (author's transl)]. Thyroid foci showing uptake on scintigraphy were examined by thermography and compared with foci showing no uptake. The following results were obtained: 1. One fifth of scintigraphically \"cold\" foci were also cold on the thermogram. 2. Two thirds to four fifths of foci showing scintigraphic uptake appeared as warm spots on the thermogram. 3. 10% of foci showing no uptake appeared as thermographic circumscribed hot spots. The combination of findings in \"3\" is suspicious of malignancy and this justifies the use of thermography in addition to scintigraphy and cytology."} {"id": "PMID:153295", "title": "[Galacto-biopsy (author's transl)].", "content": "By galacto-biopsy we understand the expression of a suspected intraductal papilloma by firm palpation as part of preparation for galactography. Using galacto-biopsy the accuracy of galactography in the diagnoses of intraduct papillomas was increased to 95%.", "contents": "[Galacto-biopsy (author's transl)]. By galacto-biopsy we understand the expression of a suspected intraductal papilloma by firm palpation as part of preparation for galactography. Using galacto-biopsy the accuracy of galactography in the diagnoses of intraduct papillomas was increased to 95%."} {"id": "PMID:153303", "title": "[Correlation the laevocardiogram and plain chest films in the presence of myocardial insufficiency (author's transl)].", "content": "A correlation was attempted in 106 patients with myocardial insufficiency between linear and volume parameters of the laevocardiogram and the corresponding parameters on plain chest films, as well as between pressure measurements and the degree of pulmonary congestion. Measurements on the plain radiograph provide only limited information on the function of the myocardium and the severity of myocardial lesion respectively. Nevertheless, they are of some value during the course of the disease.", "contents": "[Correlation the laevocardiogram and plain chest films in the presence of myocardial insufficiency (author's transl)]. A correlation was attempted in 106 patients with myocardial insufficiency between linear and volume parameters of the laevocardiogram and the corresponding parameters on plain chest films, as well as between pressure measurements and the degree of pulmonary congestion. Measurements on the plain radiograph provide only limited information on the function of the myocardium and the severity of myocardial lesion respectively. Nevertheless, they are of some value during the course of the disease."} {"id": "PMID:153304", "title": "[Coronary calcification and luminal diameter in coronary disease (author's transl)].", "content": "Two hundred and thirty-six patients with coronary heart disease were examined by coronary angiography and laevo-cardiography. In 111 patients (47%) there was coronary artery calcification. Of these, 108 patients (97%) showed abnormal findings on the coronary angiogram; in 72 patients (67%) coronary stenosis was greater than or equal to 50% of the lumen. The severity of the stenoses increased with the amount of calcification. There were only three false positive findings and the presence of coronary calcification indicates coronary sclerosis with a high degree of probability. Fluoroscopy is the simplest and most sensitive method of examination and is of great value in the non-invasive investigation of coronary sclerosis.", "contents": "[Coronary calcification and luminal diameter in coronary disease (author's transl)]. Two hundred and thirty-six patients with coronary heart disease were examined by coronary angiography and laevo-cardiography. In 111 patients (47%) there was coronary artery calcification. Of these, 108 patients (97%) showed abnormal findings on the coronary angiogram; in 72 patients (67%) coronary stenosis was greater than or equal to 50% of the lumen. The severity of the stenoses increased with the amount of calcification. There were only three false positive findings and the presence of coronary calcification indicates coronary sclerosis with a high degree of probability. Fluoroscopy is the simplest and most sensitive method of examination and is of great value in the non-invasive investigation of coronary sclerosis."} {"id": "PMID:153305", "title": "[Results of employing single crystal gammacamera and minicomputer in the first tracer passage to determine left-ventricular ejection fraction and wall motion (author's transl)].", "content": "Single crystal gammacamera and minicomputer were employed in 71 patients to determine left-ventricular ejection fraction (EF) (17 mCi 99mTc-HSA; 30 degrees RAO projection) by means of the first tracer passage. In 30 out of these patients, ventricular wall motion could be analyzed additionally because later on the gammacamera was equipped with a converging collimator. Comparison with cineventriculographically determined EF values revealed a good correlation (r = 0.91), not depending on left-ventricular wall motion pattern. Hereby, with first transit, high EFs were computed somewhat lower and low EFs were found somewhat higher. This non-limiting discrepancy is closely related to the influence of paracardiac \"background\"-radioactivity. Comparative analysis of segmental wall motion demonstrated agreement in 83% of the 90 segments examined. Therefore, it can be confirmed that performance of the first tracer passage for a evaluating segmental wall motion must not mandatorily be done with a multicrystal camera.", "contents": "[Results of employing single crystal gammacamera and minicomputer in the first tracer passage to determine left-ventricular ejection fraction and wall motion (author's transl)]. Single crystal gammacamera and minicomputer were employed in 71 patients to determine left-ventricular ejection fraction (EF) (17 mCi 99mTc-HSA; 30 degrees RAO projection) by means of the first tracer passage. In 30 out of these patients, ventricular wall motion could be analyzed additionally because later on the gammacamera was equipped with a converging collimator. Comparison with cineventriculographically determined EF values revealed a good correlation (r = 0.91), not depending on left-ventricular wall motion pattern. Hereby, with first transit, high EFs were computed somewhat lower and low EFs were found somewhat higher. This non-limiting discrepancy is closely related to the influence of paracardiac \"background\"-radioactivity. Comparative analysis of segmental wall motion demonstrated agreement in 83% of the 90 segments examined. Therefore, it can be confirmed that performance of the first tracer passage for a evaluating segmental wall motion must not mandatorily be done with a multicrystal camera."} {"id": "PMID:153306", "title": "[The oblique projection in lung perfusion scintigraphy (author's transl)].", "content": "In perfusion lung imaging by scintillation camera routine use of posterior oblique views is recommended in addition to anterior and posterior views. Avoiding overlap activity (\"shine through\") from the contralateral lung they improve the detection rate as well as the characterisation and localisation of perfusion defects especially in the lower lobes. Artifacts due to increased absorption in the scapular region or to compression by mediastinal structures should be recognized.", "contents": "[The oblique projection in lung perfusion scintigraphy (author's transl)]. In perfusion lung imaging by scintillation camera routine use of posterior oblique views is recommended in addition to anterior and posterior views. Avoiding overlap activity (\"shine through\") from the contralateral lung they improve the detection rate as well as the characterisation and localisation of perfusion defects especially in the lower lobes. Artifacts due to increased absorption in the scapular region or to compression by mediastinal structures should be recognized."} {"id": "PMID:153307", "title": "[Acute aortic thrombosis (author's transl)].", "content": "A case of acute thrombosis of the aorta is described; it extended from the superior mesenteric artery to the bifurkation and was probably due to oestrogen medication. The clinical features and diagnosis of this rare condition are described. The condition usually develops against a background of advanced arteriosclerosis and is initiated by certain haemodynamic factors such as intimal damage from blunt trauma, emboli or the thrombogenic effect of oestrogens. The symptoms, such as pain, absent pulses etcetera are the result of ischaemia and depend on the extent of the lesion. A definite radiological diagnosis can only be made by means of aortography, if necessary with oblique projections. The Seldinger technique with a femoral or axillary approach is the method of choice. Aortography shows a filling defect and occasionally a collateral circulation.", "contents": "[Acute aortic thrombosis (author's transl)]. A case of acute thrombosis of the aorta is described; it extended from the superior mesenteric artery to the bifurkation and was probably due to oestrogen medication. The clinical features and diagnosis of this rare condition are described. The condition usually develops against a background of advanced arteriosclerosis and is initiated by certain haemodynamic factors such as intimal damage from blunt trauma, emboli or the thrombogenic effect of oestrogens. The symptoms, such as pain, absent pulses etcetera are the result of ischaemia and depend on the extent of the lesion. A definite radiological diagnosis can only be made by means of aortography, if necessary with oblique projections. The Seldinger technique with a femoral or axillary approach is the method of choice. Aortography shows a filling defect and occasionally a collateral circulation."} {"id": "PMID:153308", "title": "[A comparative study between postmortem venography and the pathological anatomy of the liver (author's transl)].", "content": "A barium sulphate-gelatine mixture was injected into the veins in the left lobe of 50 human livers which were then x-rayed. The radiographs were compared with the pathological and anatomical findings and enlargements were studied and compared with the histology. A correlation was found between the venogram and the macroscopic and microscopic changes, particularly in various forms of cirrhosis of the liver. The scope and limitations of hepatic venography were studied with respect to solitary and diffuse liver metastase.", "contents": "[A comparative study between postmortem venography and the pathological anatomy of the liver (author's transl)]. A barium sulphate-gelatine mixture was injected into the veins in the left lobe of 50 human livers which were then x-rayed. The radiographs were compared with the pathological and anatomical findings and enlargements were studied and compared with the histology. A correlation was found between the venogram and the macroscopic and microscopic changes, particularly in various forms of cirrhosis of the liver. The scope and limitations of hepatic venography were studied with respect to solitary and diffuse liver metastase."} {"id": "PMID:153309", "title": "[Intravenous cholangiography in hyperbilirubinaemia (author's transl)].", "content": "The effect of bilirubin on biliary and renal excretion of methylglucamine-iodipamide at an infusion rate of 1.3, 2.6 and 5.2 mu mol/min/kg was studied by intravenous injection into five dogs with normal liver functions and chronic duodenal fistulas. Unconjugated bilirubin administered in a dose of 0.1 mu mol/min/kg reduced biliary iodipamide excretion and concentration significantly, but did not affect renal contrast material excretion. This indicates that the unsatisficatory radiological results of intravenous cholangiography in hepatic and obstructive jaundice depend not only on the reduced excretion capacity of the liver, but are also due to a direct inhibitory effect of bilirubin on biliary contrast material excretion. In the presence of hyperbilirubinaemia, the highest iodine concentrations in the bile were obtained with the highest iodipamide serum levels; a reduction in contrast material dose or prolongation of the period of contrast material infusion therefore does not appear to be indicated in jaundiced patients.", "contents": "[Intravenous cholangiography in hyperbilirubinaemia (author's transl)]. The effect of bilirubin on biliary and renal excretion of methylglucamine-iodipamide at an infusion rate of 1.3, 2.6 and 5.2 mu mol/min/kg was studied by intravenous injection into five dogs with normal liver functions and chronic duodenal fistulas. Unconjugated bilirubin administered in a dose of 0.1 mu mol/min/kg reduced biliary iodipamide excretion and concentration significantly, but did not affect renal contrast material excretion. This indicates that the unsatisficatory radiological results of intravenous cholangiography in hepatic and obstructive jaundice depend not only on the reduced excretion capacity of the liver, but are also due to a direct inhibitory effect of bilirubin on biliary contrast material excretion. In the presence of hyperbilirubinaemia, the highest iodine concentrations in the bile were obtained with the highest iodipamide serum levels; a reduction in contrast material dose or prolongation of the period of contrast material infusion therefore does not appear to be indicated in jaundiced patients."} {"id": "PMID:153310", "title": "[Computer tomographic diagnosis of abscesses (author's transl)].", "content": "The computer tomographic diagnosis of an abscess must be related to the clinical condition of a patient. In the presence of pyaemia or following an operation, with high fever, tenderness on palpation, leucocytosis and rapid development of the illness, an abscess may be suspected. The computer tomographic findings depend on the stage of the development of the abscess. Early on there is the finding of a cellular tumour with high attenuation values; after a few days, with leucocyte degeneration, there is a significant reduction in the attenuation value to that of serus fluid, or even less. Later, when organisation takes place, the development of connective tissue causes a marked increase in attenuation values which correspond with those of solid tissues. If the abscess becomes encapsulated, or if there is caseation in a tuberculous lesion, a cyst may be imitated with, again, a reduction in attenuation values. The usefulness of contrast examinations is discussed.", "contents": "[Computer tomographic diagnosis of abscesses (author's transl)]. The computer tomographic diagnosis of an abscess must be related to the clinical condition of a patient. In the presence of pyaemia or following an operation, with high fever, tenderness on palpation, leucocytosis and rapid development of the illness, an abscess may be suspected. The computer tomographic findings depend on the stage of the development of the abscess. Early on there is the finding of a cellular tumour with high attenuation values; after a few days, with leucocyte degeneration, there is a significant reduction in the attenuation value to that of serus fluid, or even less. Later, when organisation takes place, the development of connective tissue causes a marked increase in attenuation values which correspond with those of solid tissues. If the abscess becomes encapsulated, or if there is caseation in a tuberculous lesion, a cyst may be imitated with, again, a reduction in attenuation values. The usefulness of contrast examinations is discussed."} {"id": "PMID:153311", "title": "[Value and results of computer tomography in diseases of the pancreas (author's transl)].", "content": "In a joint study carried out by the radiological university clinics of Bonn, Hamburg, Cologne, Leuven and Munich, 483 computer tomographs of the pancreas were evaluated. A correct histological diagnosis, or one confirmed at surgery, was obtained in 74.5% of 168 cases; in a further 9% an abnormality was seen in the pancreas or in its immediate vicinity, but was wrongly interpreted. The computer tomographic criteria of inflammatory processes and of tumours of the pancreas are given, and the not uncommon difficulties in distinguishing between these are discussed.", "contents": "[Value and results of computer tomography in diseases of the pancreas (author's transl)]. In a joint study carried out by the radiological university clinics of Bonn, Hamburg, Cologne, Leuven and Munich, 483 computer tomographs of the pancreas were evaluated. A correct histological diagnosis, or one confirmed at surgery, was obtained in 74.5% of 168 cases; in a further 9% an abnormality was seen in the pancreas or in its immediate vicinity, but was wrongly interpreted. The computer tomographic criteria of inflammatory processes and of tumours of the pancreas are given, and the not uncommon difficulties in distinguishing between these are discussed."} {"id": "PMID:153312", "title": "[Quantitative determination of the effect of angiotensin on renal blood flow (author's transl)].", "content": "The effect of angiotensin on renal blood flow was measured in ten patients by using selected angiography and video densitometry. A dose of 0.5 microgram. reduced flow in the renal artery 30 seconds after intraarterial application by an average of 60%. Neither the renal artery nor its primary branches showed any change in calibre.", "contents": "[Quantitative determination of the effect of angiotensin on renal blood flow (author's transl)]. The effect of angiotensin on renal blood flow was measured in ten patients by using selected angiography and video densitometry. A dose of 0.5 microgram. reduced flow in the renal artery 30 seconds after intraarterial application by an average of 60%. Neither the renal artery nor its primary branches showed any change in calibre."} {"id": "PMID:153313", "title": "[A new instrument for catheter introduction for angiographic and percutaneous transhepatic examinations (author's transl)].", "content": "An instrument is described which can be used in the femoral or axillary approach using the Seldinger technique, and which has been found to be satisfactory during several years' use. Its advantages are that it is easy to use and the necessary technique is easily acquired; catheters can be changed painlessly and without damaging the artery; thinner catherters can be introduced without producing bleeding and the space between the instrument and the catheter can be perfused. The instrument has also proved valuable for percutaneous transhepatic biliary drainage or portography by preventing buckling of the catheter at the costal chest/liver interface.", "contents": "[A new instrument for catheter introduction for angiographic and percutaneous transhepatic examinations (author's transl)]. An instrument is described which can be used in the femoral or axillary approach using the Seldinger technique, and which has been found to be satisfactory during several years' use. Its advantages are that it is easy to use and the necessary technique is easily acquired; catheters can be changed painlessly and without damaging the artery; thinner catherters can be introduced without producing bleeding and the space between the instrument and the catheter can be perfused. The instrument has also proved valuable for percutaneous transhepatic biliary drainage or portography by preventing buckling of the catheter at the costal chest/liver interface."} {"id": "PMID:153314", "title": "[Osteoarthritis in the neonate. Radiologic diagnosis and follow-up observations (author's transl)].", "content": "A fatally ending index case of septic osteoarthritis that was diagnosed retrospectively initiated this report. This patient had severe, asymmetrically distributed metaphyseal growth disturbances at many long bones. In order to determine the features of early radiologic diagnosis we report the findings of 7 further patients with neonatal septic osteoarthritis with clinical and radiological follow-up. The most important observation for early radiologic diagnosis of osteoarthritis is the displacement of fat layers along the metaphysis. Other findings of the soft tissues have the same diagnostic value as bone destruction and subperiosteal new bone formation found one to three weeks later on roentgenfilms. Detecting early signs of osteoarthritis helps in localizing the focus for bacteriologic diagnosis, which is said to be more successful than blood cultures. Diagnosing a joint empyema initiates surgical intervention for pressure relief in order to avoid necrosis of the epiphysis as seen in the femoral head in septic arthritis of the hip joint. Early diagnosis and treatment prior to destruction of the growing cartilage is necessary to avoid growth disturbances and length discrepancies of long bones. In cases of sepsis a so called \"babygram\" and a repeat examination 10 to 14 days later is mandatory.", "contents": "[Osteoarthritis in the neonate. Radiologic diagnosis and follow-up observations (author's transl)]. A fatally ending index case of septic osteoarthritis that was diagnosed retrospectively initiated this report. This patient had severe, asymmetrically distributed metaphyseal growth disturbances at many long bones. In order to determine the features of early radiologic diagnosis we report the findings of 7 further patients with neonatal septic osteoarthritis with clinical and radiological follow-up. The most important observation for early radiologic diagnosis of osteoarthritis is the displacement of fat layers along the metaphysis. Other findings of the soft tissues have the same diagnostic value as bone destruction and subperiosteal new bone formation found one to three weeks later on roentgenfilms. Detecting early signs of osteoarthritis helps in localizing the focus for bacteriologic diagnosis, which is said to be more successful than blood cultures. Diagnosing a joint empyema initiates surgical intervention for pressure relief in order to avoid necrosis of the epiphysis as seen in the femoral head in septic arthritis of the hip joint. Early diagnosis and treatment prior to destruction of the growing cartilage is necessary to avoid growth disturbances and length discrepancies of long bones. In cases of sepsis a so called \"babygram\" and a repeat examination 10 to 14 days later is mandatory."} {"id": "PMID:153315", "title": "[Quantitative mineral estimations in vertebral bodies by computer tomography (author's transl)].", "content": "The accuracy of computer tomographic bone density measurements in the axial skeleton was tested by comparing results obtained from the first lumbar body in abdominal phantoms. An almost linear relationship (r = 0.998) was found between increasing concentrations of a calcium chloride solution and CT absorption values. The sum of the CT values of sections through the vertebral body correlated well with their ash content (r = 0.90) as well as with the hydroxyl apatite values obtained by I125-absorption densitometry (r = 0.88). Reproducibility of CT measurements on the phantom was good (coefficient of variation = 1.2% in the spongiosa). Average CT values of separate measurements of the spongiosa and cortex could be correlated with the total spongiosa by a special programme (r = 0.95). In the practical application of this technique, possible sources of error must be considered, such as the effect of high energy polychromatic radiation, inhomogeneity of the object being investigated and difficulties in positioning the patients", "contents": "[Quantitative mineral estimations in vertebral bodies by computer tomography (author's transl)]. The accuracy of computer tomographic bone density measurements in the axial skeleton was tested by comparing results obtained from the first lumbar body in abdominal phantoms. An almost linear relationship (r = 0.998) was found between increasing concentrations of a calcium chloride solution and CT absorption values. The sum of the CT values of sections through the vertebral body correlated well with their ash content (r = 0.90) as well as with the hydroxyl apatite values obtained by I125-absorption densitometry (r = 0.88). Reproducibility of CT measurements on the phantom was good (coefficient of variation = 1.2% in the spongiosa). Average CT values of separate measurements of the spongiosa and cortex could be correlated with the total spongiosa by a special programme (r = 0.95). In the practical application of this technique, possible sources of error must be considered, such as the effect of high energy polychromatic radiation, inhomogeneity of the object being investigated and difficulties in positioning the patients"} {"id": "PMID:153316", "title": "[Technique and diagnostic value of functional myelography in lumbar discopathy (author's transl)].", "content": "A standard myelogram using water soluble contrast with additional functional examination were carried out on 72 patients with suspected disc prolapse. Diagnostic accuracy can be significantly improved by the functional examination and, in some cases, the diagnosis can only be made in this way. There are no false positives. The advantages and limitations of the method are enumerated and its morphological significance is discussed.", "contents": "[Technique and diagnostic value of functional myelography in lumbar discopathy (author's transl)]. A standard myelogram using water soluble contrast with additional functional examination were carried out on 72 patients with suspected disc prolapse. Diagnostic accuracy can be significantly improved by the functional examination and, in some cases, the diagnosis can only be made in this way. There are no false positives. The advantages and limitations of the method are enumerated and its morphological significance is discussed."} {"id": "PMID:153317", "title": "[Discographic visualisation of lumbar disc herniations (author's transl)].", "content": "The myelographic diagnosis of lumbar disc herniations remains unclear in about 5% of the cases. When the clinical examination does not allow clear localisation of the segmental level of the lesion and symptomatology is atypical, discorgraphy may be the only procedure providing further diagnostic information. Very lateral as well as ventral disc herniations can thus be clearly demonstrated. Knowledge of both typical and atypical findings is, however, required to avoid false negative results.", "contents": "[Discographic visualisation of lumbar disc herniations (author's transl)]. The myelographic diagnosis of lumbar disc herniations remains unclear in about 5% of the cases. When the clinical examination does not allow clear localisation of the segmental level of the lesion and symptomatology is atypical, discorgraphy may be the only procedure providing further diagnostic information. Very lateral as well as ventral disc herniations can thus be clearly demonstrated. Knowledge of both typical and atypical findings is, however, required to avoid false negative results."} {"id": "PMID:153318", "title": "[The angiographic demonstration of infra-tentorial tumors with identical manifestations, localisation and histology in identical twins (author's transl)].", "content": "The angiographic diagnostic features of concordant tumors of the posterior fossa in monozygotic twins are described. In both cotwins cranio-spinal subependymomas were found which had grown through the foramen magnum and reached from the fourth ventricle down to the second cervical vertebra. Thereby, the conformity of the clinical mainifestation, symptomotology and the course of the disease, the localisation and extent of the tumors as well as the neuroradiologic findings and the histologic features of the tumors were particularly striking. After a review and critical summary of the few cases of concordant affections with brain tumors in identical twins published in the literature at present our couple is discussed under the question of the possible influence of genetic factors or a hereditary disposition on the development of cerebral tumors.", "contents": "[The angiographic demonstration of infra-tentorial tumors with identical manifestations, localisation and histology in identical twins (author's transl)]. The angiographic diagnostic features of concordant tumors of the posterior fossa in monozygotic twins are described. In both cotwins cranio-spinal subependymomas were found which had grown through the foramen magnum and reached from the fourth ventricle down to the second cervical vertebra. Thereby, the conformity of the clinical mainifestation, symptomotology and the course of the disease, the localisation and extent of the tumors as well as the neuroradiologic findings and the histologic features of the tumors were particularly striking. After a review and critical summary of the few cases of concordant affections with brain tumors in identical twins published in the literature at present our couple is discussed under the question of the possible influence of genetic factors or a hereditary disposition on the development of cerebral tumors."} {"id": "PMID:153319", "title": "[Studies on the diagnostic accuracy of lymphography (author's transl)].", "content": "Contradictory reports in the literature on the reliability of lymphography stimulated the authors to test the diagnostic accuracy, employing methods which are approximately analogous to practice, using carcinoma of the cervix as the model on which the study was carried out. Using 21 observers it was found that there was no correlation between their experience and on-target accuracy of the diagnosis. Good observers obtained an accuracy of 85% with good proportions between sensitivity in the recognition of detail, specificity and readiness to arrive at a decision on the basis of discriminatory ability. With the help of the concept of the ROC curves, the position taken up by the observers in respect of diagnostic decisions, and a complex manner of assessing the various characteristic factors determining diagnostic accuracy, are demonstrated. This form of test, which permits manipulation of different variants of diagnosis, is recommended, among other things, for performance control at the end of training and continuing education courses in other fields of x-ray diagnosis as well.", "contents": "[Studies on the diagnostic accuracy of lymphography (author's transl)]. Contradictory reports in the literature on the reliability of lymphography stimulated the authors to test the diagnostic accuracy, employing methods which are approximately analogous to practice, using carcinoma of the cervix as the model on which the study was carried out. Using 21 observers it was found that there was no correlation between their experience and on-target accuracy of the diagnosis. Good observers obtained an accuracy of 85% with good proportions between sensitivity in the recognition of detail, specificity and readiness to arrive at a decision on the basis of discriminatory ability. With the help of the concept of the ROC curves, the position taken up by the observers in respect of diagnostic decisions, and a complex manner of assessing the various characteristic factors determining diagnostic accuracy, are demonstrated. This form of test, which permits manipulation of different variants of diagnosis, is recommended, among other things, for performance control at the end of training and continuing education courses in other fields of x-ray diagnosis as well."} {"id": "PMID:153320", "title": "[Modern therapy of acne vulgaris. A therapy proposal for the management of uncomplicated cases].", "content": "Acne vulgaris is one of the most widespread of all diseases and is frequently the object of treatment in general and specialist medical practice. New insights into the pathophysiology of acne show that the most important therapeutic principle is suppression of the propionibacteria in the pilosebaceous duct since these bacteria have a key role in the genesis of the comedo and of inflammatory acne efflorescences. Experimental findings are shown which prove the value of a local treatment with antibiotics and ethanol-containing masks. The second therapeutic principle is \"keratolytic\" therapy. Retinoic acid, benzoyl peroxide and salicylic acid are in the forefront here. The third therapeutic principle is the reduction of seborrhea. Benzoyl peroxide is especially suitable for local treatment. Differential diagnosis of acne vulgaris and additional possibilities of treatment in problem cases are dealt with.", "contents": "[Modern therapy of acne vulgaris. A therapy proposal for the management of uncomplicated cases]. Acne vulgaris is one of the most widespread of all diseases and is frequently the object of treatment in general and specialist medical practice. New insights into the pathophysiology of acne show that the most important therapeutic principle is suppression of the propionibacteria in the pilosebaceous duct since these bacteria have a key role in the genesis of the comedo and of inflammatory acne efflorescences. Experimental findings are shown which prove the value of a local treatment with antibiotics and ethanol-containing masks. The second therapeutic principle is \"keratolytic\" therapy. Retinoic acid, benzoyl peroxide and salicylic acid are in the forefront here. The third therapeutic principle is the reduction of seborrhea. Benzoyl peroxide is especially suitable for local treatment. Differential diagnosis of acne vulgaris and additional possibilities of treatment in problem cases are dealt with."} {"id": "PMID:153323", "title": "On the peripheral location of the Y chromosome.", "content": "The location of the Y chromosome in metaphase spreads is studied in groups of (a) 96 normal males, (b) 17 Down's syndrome patients, and (c) 51 patients with Klinefelter's syndrome. The position of the Y is scored as either peripheral or nonperipheral using several of the traditional definitions found in the literature. It is shown that contradictory results may be obtained depending on the particular definition employed and that none of the available definitions capture the essence of the meaning of 'peripheral'. Therefore a new, standardized definition is introduced-one that applies to both circular and noncircular spreads. Using this new definition, we find definite intergroup variability. The Y is peripheral in normal males, but not in either the Down's or Klinefelter's samples.", "contents": "On the peripheral location of the Y chromosome. The location of the Y chromosome in metaphase spreads is studied in groups of (a) 96 normal males, (b) 17 Down's syndrome patients, and (c) 51 patients with Klinefelter's syndrome. The position of the Y is scored as either peripheral or nonperipheral using several of the traditional definitions found in the literature. It is shown that contradictory results may be obtained depending on the particular definition employed and that none of the available definitions capture the essence of the meaning of 'peripheral'. Therefore a new, standardized definition is introduced-one that applies to both circular and noncircular spreads. Using this new definition, we find definite intergroup variability. The Y is peripheral in normal males, but not in either the Down's or Klinefelter's samples."} {"id": "PMID:153324", "title": "Rapid identification of chromosomes carrying silver-stained nucleolus-organizing regions: application to case of 21/21 Robertsonian translocation.", "content": "The use of a combination of transmitted light and epiluminescence after silver and fluorescent staining of chromosome preparations makes it possible to achieve simultaneous visualization of silver-stained NORs and flourescent chromosomes. This technique permits exact localization of silver precipitates on normal and BrdU-substituted chromosomes. After previous silver impregnation, fluorescent staining by actinomycin-daunomycin-DAPI was used to induce a banding pattern that enables identification of specific chromosomes while observing silver-stained NORs at the same time. Application of this method to a Down's syndrome patient revealed a 21/21 Robertsonian translocation with NOR'S eliminated.", "contents": "Rapid identification of chromosomes carrying silver-stained nucleolus-organizing regions: application to case of 21/21 Robertsonian translocation. The use of a combination of transmitted light and epiluminescence after silver and fluorescent staining of chromosome preparations makes it possible to achieve simultaneous visualization of silver-stained NORs and flourescent chromosomes. This technique permits exact localization of silver precipitates on normal and BrdU-substituted chromosomes. After previous silver impregnation, fluorescent staining by actinomycin-daunomycin-DAPI was used to induce a banding pattern that enables identification of specific chromosomes while observing silver-stained NORs at the same time. Application of this method to a Down's syndrome patient revealed a 21/21 Robertsonian translocation with NOR'S eliminated."} {"id": "PMID:153325", "title": "Inversions and other unusual heteromorphisms detected by C-banding.", "content": "Sixteen patients with unusual heteromorphisms involving alterations of the length and/or position of centromeric heterochromatin are described. Family studies showed that the heteromorphisms were present in other relatives and segregated in the expected 1:1 ratio. There was a significantly greater frequency of unusual heteromorphisms among Orientals than in other races studied.", "contents": "Inversions and other unusual heteromorphisms detected by C-banding. Sixteen patients with unusual heteromorphisms involving alterations of the length and/or position of centromeric heterochromatin are described. Family studies showed that the heteromorphisms were present in other relatives and segregated in the expected 1:1 ratio. There was a significantly greater frequency of unusual heteromorphisms among Orientals than in other races studied."} {"id": "PMID:153332", "title": "Lung lysophospholipase activity in specific-pathogen-free rats infected with Pasteurella pneumotropica or Mycoplasma pulmonis.", "content": "The effects of Pasteurella pneumotropica and Mycoplasma pulmonis infections in specific-pathogen-free rats were studied to determine whether or not bacterial infections could cause an increase in rat lung lysophospholipase activity and/or changes in bone marrow eosinophil levels. Lung lysophospholipase activity levels of M. pulmonis-infected rats were elevated with increasing infection dosages, but enzyme levels were not accompanied by a lung tissue eosinophilia or an increase in bone marrow eosinophils. Rats infected with P. pneumotropica showed neither an increased lung lysophospholipase activity level nor an increased tissue or bone marrow eosinophilia.", "contents": "Lung lysophospholipase activity in specific-pathogen-free rats infected with Pasteurella pneumotropica or Mycoplasma pulmonis. The effects of Pasteurella pneumotropica and Mycoplasma pulmonis infections in specific-pathogen-free rats were studied to determine whether or not bacterial infections could cause an increase in rat lung lysophospholipase activity and/or changes in bone marrow eosinophil levels. Lung lysophospholipase activity levels of M. pulmonis-infected rats were elevated with increasing infection dosages, but enzyme levels were not accompanied by a lung tissue eosinophilia or an increase in bone marrow eosinophils. Rats infected with P. pneumotropica showed neither an increased lung lysophospholipase activity level nor an increased tissue or bone marrow eosinophilia."} {"id": "PMID:153333", "title": "Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum.", "content": "To better define the role of bacteria in inflammatory acne vulgaris, we have investigated the ability of four strains of Propionibacterium acnes and three strains of Propionibacterium granulosum to activate complement. Complement activation was assayed by incubating normal human serum with varying concentrations of each strain and measuring residual total hemolytic complement activity. When serum was tested unaltered, P. acnes strains were approximately threefold more potent than an equal weight of P. granulosum in consuming complement, which could reflect classical and/or alternative pathway activation. All strains also consumed complement in serum chelated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, which selectively assays alternative pathway activation. Incubation of unaltered serum with both P. acnes and P. granulosum resulted in immunoelectrophoretic conversion of C4, C3, and factor B of the alternative pathway. Incubation of chelated serum resulted in conversion of C3 and factor B. These data taken together suggest that both species can activate complement through either pathway. Serum incubated with P. acnes was chemotactic for polymorphonuclear leukocytes, and this chemotactic activity was largely C5 dependent as shown by antibody inhibition. It is suggested that complement activation may occur in vivo in acne, and the inflammatory response may be contributed to by the generation of C5-dependent chemotactic factors.", "contents": "Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum. To better define the role of bacteria in inflammatory acne vulgaris, we have investigated the ability of four strains of Propionibacterium acnes and three strains of Propionibacterium granulosum to activate complement. Complement activation was assayed by incubating normal human serum with varying concentrations of each strain and measuring residual total hemolytic complement activity. When serum was tested unaltered, P. acnes strains were approximately threefold more potent than an equal weight of P. granulosum in consuming complement, which could reflect classical and/or alternative pathway activation. All strains also consumed complement in serum chelated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, which selectively assays alternative pathway activation. Incubation of unaltered serum with both P. acnes and P. granulosum resulted in immunoelectrophoretic conversion of C4, C3, and factor B of the alternative pathway. Incubation of chelated serum resulted in conversion of C3 and factor B. These data taken together suggest that both species can activate complement through either pathway. Serum incubated with P. acnes was chemotactic for polymorphonuclear leukocytes, and this chemotactic activity was largely C5 dependent as shown by antibody inhibition. It is suggested that complement activation may occur in vivo in acne, and the inflammatory response may be contributed to by the generation of C5-dependent chemotactic factors."} {"id": "PMID:153334", "title": "Mucopolysaccharide material resulting from the interaction of Treponema pallidum (Nichols strain) with cultured mammalian cells.", "content": "During incubation of Treponema pallidum (Nichols strain) with cultured mammlian cells derived from normal rabbit testes (NRT), an amorphous material accumulated at the surface of the cultured cells. This material was randomly distributed on all tissue cells within the culture chambers. The amount of amorphous material was dependent on the treponemal inocula. With 3 x 10(8) organisms per ml, this material was readily apparent within 2 days; with 4 x 10(7) organisms per ml, this material was detectable within 4 to 5 days; with lower inocula, the accumulation of amorphous material was far less apparent. Deposition of this surface-associated material required attachment of treponemes to the cultured cells, and the amount deposited was related to the number of treponemes attached per cell. This amorphous material was not detected when NRT cells were incubated with preparations of T. pallidum that were heat or air inactivated. In addition, the accumulaton of amorphous material was not due to a soluble component from host testicular tissue or to a soluble component developing during treponemal infection. This was demonstrated by the inability of membrane filtered preparations of T. pallidum to induce the deposition of amorphous material at the surface of the cultured cells. The nature of this material appeared to be acidic mucopolysaccharide as indicated by its metachromatic staining properties, its stainability with ruthenium red, and its partial degradation by bovine and streptomyces hyaluronidase. This amorphous material that accumulated in vitro at the surface of cultured cells may be similar to the mucoid material that accumulates in vivo during syphilitic infection.", "contents": "Mucopolysaccharide material resulting from the interaction of Treponema pallidum (Nichols strain) with cultured mammalian cells. During incubation of Treponema pallidum (Nichols strain) with cultured mammlian cells derived from normal rabbit testes (NRT), an amorphous material accumulated at the surface of the cultured cells. This material was randomly distributed on all tissue cells within the culture chambers. The amount of amorphous material was dependent on the treponemal inocula. With 3 x 10(8) organisms per ml, this material was readily apparent within 2 days; with 4 x 10(7) organisms per ml, this material was detectable within 4 to 5 days; with lower inocula, the accumulation of amorphous material was far less apparent. Deposition of this surface-associated material required attachment of treponemes to the cultured cells, and the amount deposited was related to the number of treponemes attached per cell. This amorphous material was not detected when NRT cells were incubated with preparations of T. pallidum that were heat or air inactivated. In addition, the accumulaton of amorphous material was not due to a soluble component from host testicular tissue or to a soluble component developing during treponemal infection. This was demonstrated by the inability of membrane filtered preparations of T. pallidum to induce the deposition of amorphous material at the surface of the cultured cells. The nature of this material appeared to be acidic mucopolysaccharide as indicated by its metachromatic staining properties, its stainability with ruthenium red, and its partial degradation by bovine and streptomyces hyaluronidase. This amorphous material that accumulated in vitro at the surface of cultured cells may be similar to the mucoid material that accumulates in vivo during syphilitic infection."} {"id": "PMID:153335", "title": "Lymphocyte transformation test in leprosy: decreased lymphocyte reactivity to Mycobacterium leprae in lepromatous leprosy, with no evidence for a generalized impairment.", "content": "Untreated leprosy patients were examined with respect to lymphocyte transformation in vitro after stimulation with mycobacterial and other microbial antigens, allogeneic lymphocytes, or nonspecific mitogens. Methods were used to circumvent technical variability. The results were compared with those obtained in controls matched for age, sex, race, and environment. No evidence was found for a generalized impairment of lymphocyte transformation in vitro, whereas a specific defect towards Mycobacterium leprae was demonstrable in lepromatous leprosy patients. The response to M. leprae, investigated in untreated and treated leprosy patients, decreased along the leprosy spectrum. Moreover, the results of the one-way mixed lymphocyte cultures showed that lymphocytes from leprosy patients had a normal stimulator and responder capacity, when they were tested against a panel of allogeneic lymphocytes. The influence of serum factors was investigated in untreated leprosy patients in the mixed lymphocyte culture. On average, tuberculoid as well as lepromatous sera showed a low-level depressive effect, but some sera showed a stimulatory effect. Therefore, a depressive effect of serum factors cannot be considered to be a general feature of leprosy. The correlation between the Mitsuda type of lepromin skin test and the lymphocyte reactivity in vitro to M. leprae was studied, and a positive correlation was found.", "contents": "Lymphocyte transformation test in leprosy: decreased lymphocyte reactivity to Mycobacterium leprae in lepromatous leprosy, with no evidence for a generalized impairment. Untreated leprosy patients were examined with respect to lymphocyte transformation in vitro after stimulation with mycobacterial and other microbial antigens, allogeneic lymphocytes, or nonspecific mitogens. Methods were used to circumvent technical variability. The results were compared with those obtained in controls matched for age, sex, race, and environment. No evidence was found for a generalized impairment of lymphocyte transformation in vitro, whereas a specific defect towards Mycobacterium leprae was demonstrable in lepromatous leprosy patients. The response to M. leprae, investigated in untreated and treated leprosy patients, decreased along the leprosy spectrum. Moreover, the results of the one-way mixed lymphocyte cultures showed that lymphocytes from leprosy patients had a normal stimulator and responder capacity, when they were tested against a panel of allogeneic lymphocytes. The influence of serum factors was investigated in untreated leprosy patients in the mixed lymphocyte culture. On average, tuberculoid as well as lepromatous sera showed a low-level depressive effect, but some sera showed a stimulatory effect. Therefore, a depressive effect of serum factors cannot be considered to be a general feature of leprosy. The correlation between the Mitsuda type of lepromin skin test and the lymphocyte reactivity in vitro to M. leprae was studied, and a positive correlation was found."} {"id": "PMID:153340", "title": "Cytochemical observations of coelomocytes from the earthworm, Lumbricus terrestris.", "content": "Coelomocytes of the earthworm, Lumbricus terrestris, were stained by cytochemical techniques to determine the biochemical composition of the seven different cell types and subtypes. The enzymes acid phosphatase and beta-glucuronidase are present in all types of coelomocytes, but are especially abundant in basophils and neutrophils; the differences in enzyme amounts correlate well with the differences in phagocytic activity of the various cell types. No peroxidase is present. The cytoplasmic basophilia of basophils is due primarily to ribonucleic acid. Basophils also contain large deposits of glycogen, with neutrophils and chloragogen cells containing somewhat lesser amounts. The predominant granules of the two types of acidophils and of granulocytes are composed of a basic protein and a neutral mucopolysaccharide or glycoprotein. A second granule population, present in low numbers in acidophils and granulocytes, but in larger numbers in basophils and neutrophils, is small in size and lipid-positive and may, in part, represent lysosomes. Lipid is especially abundant in the vesicles and granules of the two types of chloragogen cells. Some granules of chloragogen cells also contain ferrous and ferric iron and a substance with pseudoperoxidase activity. The cytoplasm contains protein, glycogen, and a neutral mucopolysaccharide. In addition, acid mucopolysaccharides are variably present in the cytoplasm of chloragogen cells, the only coelomocytes to contain this class of substances.", "contents": "Cytochemical observations of coelomocytes from the earthworm, Lumbricus terrestris. Coelomocytes of the earthworm, Lumbricus terrestris, were stained by cytochemical techniques to determine the biochemical composition of the seven different cell types and subtypes. The enzymes acid phosphatase and beta-glucuronidase are present in all types of coelomocytes, but are especially abundant in basophils and neutrophils; the differences in enzyme amounts correlate well with the differences in phagocytic activity of the various cell types. No peroxidase is present. The cytoplasmic basophilia of basophils is due primarily to ribonucleic acid. Basophils also contain large deposits of glycogen, with neutrophils and chloragogen cells containing somewhat lesser amounts. The predominant granules of the two types of acidophils and of granulocytes are composed of a basic protein and a neutral mucopolysaccharide or glycoprotein. A second granule population, present in low numbers in acidophils and granulocytes, but in larger numbers in basophils and neutrophils, is small in size and lipid-positive and may, in part, represent lysosomes. Lipid is especially abundant in the vesicles and granules of the two types of chloragogen cells. Some granules of chloragogen cells also contain ferrous and ferric iron and a substance with pseudoperoxidase activity. The cytoplasm contains protein, glycogen, and a neutral mucopolysaccharide. In addition, acid mucopolysaccharides are variably present in the cytoplasm of chloragogen cells, the only coelomocytes to contain this class of substances."} {"id": "PMID:153341", "title": "Light and electron microscopic investigation of ATPase activity in musculature during anuran tail resorption.", "content": "The histochemical activity of adenosine triphosphatase (ATPase) was studied at light and electron microscopic levels in larval tail musculature of Rana catesbeiana and Rana ornativentris during late metamorphic stages. The presence of low, moderate or dark reaction of K2-EDTA-preincubated Ca++-ATPase was correlated with the variable degree of degeneration of white fibres even at the late stage of tail resorption. The reasons for an increase in this ATPase activity in degenerating white muscle fibres are discussed. Irrespective of the degree of degeneration, all red fibres showed high ATPase reaction. During myocytolysis, it is shown that the SR vesicles accumulate electron dense amorphous material. The degree of myofibrillar disintegration correlated with decrease in ultrastructural reaction product for Mg++-ATPase. Although grouped atrophy of muscle fibres (as seen in Xenopus laevis, den Hartog Jager et al., 1973, 1975) was absent in musculature of resorptive tails, ultrastructural characteristics including proliferation of SR and dilation of its vesicles represent alteration of the normal neural influence on the skeletal muscle fibres.", "contents": "Light and electron microscopic investigation of ATPase activity in musculature during anuran tail resorption. The histochemical activity of adenosine triphosphatase (ATPase) was studied at light and electron microscopic levels in larval tail musculature of Rana catesbeiana and Rana ornativentris during late metamorphic stages. The presence of low, moderate or dark reaction of K2-EDTA-preincubated Ca++-ATPase was correlated with the variable degree of degeneration of white fibres even at the late stage of tail resorption. The reasons for an increase in this ATPase activity in degenerating white muscle fibres are discussed. Irrespective of the degree of degeneration, all red fibres showed high ATPase reaction. During myocytolysis, it is shown that the SR vesicles accumulate electron dense amorphous material. The degree of myofibrillar disintegration correlated with decrease in ultrastructural reaction product for Mg++-ATPase. Although grouped atrophy of muscle fibres (as seen in Xenopus laevis, den Hartog Jager et al., 1973, 1975) was absent in musculature of resorptive tails, ultrastructural characteristics including proliferation of SR and dilation of its vesicles represent alteration of the normal neural influence on the skeletal muscle fibres."} {"id": "PMID:153343", "title": "Flow dependence of gas distribution and the pattern of inspiratory muscle contraction.", "content": "We measured regional distribution of xenon-133 boli at 0.25, 0.75, and 1.5 l/s in four normal seated subjects during inspirations performed predominantly with intercostal and accessory muscles (IC) or with the diaphragm, accompanied by outward abdominal motion (Ab). In six additional subjects we inferred the topographical distribution of helium boli during similar breaths and flow rates from the slope of the alveolar plateau recorded during a slow expiration (less than 0.5 l/s). Distribution of the helium boli was studied during natural as well as IC and Ab inspirations. At each of the flow rates IC breaths distributed relatively more of the inspired bolus to upper lung regions than did Ab inspirations. Natural breaths at 0.25 l/s resulted in distributions similar to those of Ab inspirations, whereas at 1.5 l/s the distribution approached that of IC inspirations. A three-compartment model, representing upper, middle, and lower lung regions, was used to simulate bolus distribution. The experimental data showed substantial departure from predictions based on regional time constants alone. However, additional small differences in applied pressure (less than 0.50 cmH2O) between the regions satisfactorily accounted for the gas distribution.", "contents": "Flow dependence of gas distribution and the pattern of inspiratory muscle contraction. We measured regional distribution of xenon-133 boli at 0.25, 0.75, and 1.5 l/s in four normal seated subjects during inspirations performed predominantly with intercostal and accessory muscles (IC) or with the diaphragm, accompanied by outward abdominal motion (Ab). In six additional subjects we inferred the topographical distribution of helium boli during similar breaths and flow rates from the slope of the alveolar plateau recorded during a slow expiration (less than 0.5 l/s). Distribution of the helium boli was studied during natural as well as IC and Ab inspirations. At each of the flow rates IC breaths distributed relatively more of the inspired bolus to upper lung regions than did Ab inspirations. Natural breaths at 0.25 l/s resulted in distributions similar to those of Ab inspirations, whereas at 1.5 l/s the distribution approached that of IC inspirations. A three-compartment model, representing upper, middle, and lower lung regions, was used to simulate bolus distribution. The experimental data showed substantial departure from predictions based on regional time constants alone. However, additional small differences in applied pressure (less than 0.50 cmH2O) between the regions satisfactorily accounted for the gas distribution."} {"id": "PMID:153345", "title": "Studies of the chemo-mechanical conversion in artificially produced streamings. III. Dynamic cooperativity--a new cooperativity in actomyosin systems with a polarized arrangement of F-actin.", "content": "The order--disorder phase transition in the chemo-mechanical process in our streaming system, which was reported in the preceding paper [Yano, M. & Shimizu, H., J. Biochem, 84, 1087--1092], was studied in detail. Starting from the hypothesis that a new type of cooperativity, dynamic cooperativity, is present in the elementary cycles of the chemo-mechanical conversion, quantitative and consistent agreement was obtained between the theoretical and experimental data on the temperature dependences of the streaming velocity and the ATPase activity, including the presence of the phase transition. The hypothesis was also supported by observations of the temperature dependence of the ATPase activity in resisted streaming. The physical and physiological significance of dynamic cooperativity is considered. It is shown that dynamic cooperativity arises in actomyosin system which have a polarized arrangement of F-actin by directed streaming of the solution, because the rate of the elementary cycle can be accelerated by the streaming. Furthermore, dynamic cooperativity is the key mechanism of self-organization of a dynamical order such that in ordered motions, and is one of the essential conditions for the direct conversion of the chemical energy of ATP to the mechanical energy of ordered and directed motion.", "contents": "Studies of the chemo-mechanical conversion in artificially produced streamings. III. Dynamic cooperativity--a new cooperativity in actomyosin systems with a polarized arrangement of F-actin. The order--disorder phase transition in the chemo-mechanical process in our streaming system, which was reported in the preceding paper [Yano, M. & Shimizu, H., J. Biochem, 84, 1087--1092], was studied in detail. Starting from the hypothesis that a new type of cooperativity, dynamic cooperativity, is present in the elementary cycles of the chemo-mechanical conversion, quantitative and consistent agreement was obtained between the theoretical and experimental data on the temperature dependences of the streaming velocity and the ATPase activity, including the presence of the phase transition. The hypothesis was also supported by observations of the temperature dependence of the ATPase activity in resisted streaming. The physical and physiological significance of dynamic cooperativity is considered. It is shown that dynamic cooperativity arises in actomyosin system which have a polarized arrangement of F-actin by directed streaming of the solution, because the rate of the elementary cycle can be accelerated by the streaming. Furthermore, dynamic cooperativity is the key mechanism of self-organization of a dynamical order such that in ordered motions, and is one of the essential conditions for the direct conversion of the chemical energy of ATP to the mechanical energy of ordered and directed motion."} {"id": "PMID:153346", "title": "Purification of modulator-deficient myosin light-chain kinase by modulator protein-Sepharose affinity chromatography.", "content": "Modulator-deficient myosin light-chain kinase from rabbit skeletal muscle was purified by modulator protein-Sepharose 4B affinity chromatography. The purified protein showed a single band (MW 80,000) on polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and it exists as a monomer in the native state as determined by gel filtration. The modulator-deficient myosin light-chain kinase (MW 80,000), modulator protein (MW 16,500) and Ca2+ were essential for the kinase activity. The half-maximal activity of the kinase in the presence of excess modulator protein with 10 mM MgCl2 was at pCa 5.1, where full activity of actomyosin-ATPase is observed in the presence of the troponin--tropomyosin system. Assuming a rapid equilibrium between myosin light-chain kinase and two substrates, ATP and g2 light-chain, Km values for ATP and g2 light chain were evaluated as 0.28 mM and 0.024 mM, respectively. Vm/e was 5.7 s-1.", "contents": "Purification of modulator-deficient myosin light-chain kinase by modulator protein-Sepharose affinity chromatography. Modulator-deficient myosin light-chain kinase from rabbit skeletal muscle was purified by modulator protein-Sepharose 4B affinity chromatography. The purified protein showed a single band (MW 80,000) on polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and it exists as a monomer in the native state as determined by gel filtration. The modulator-deficient myosin light-chain kinase (MW 80,000), modulator protein (MW 16,500) and Ca2+ were essential for the kinase activity. The half-maximal activity of the kinase in the presence of excess modulator protein with 10 mM MgCl2 was at pCa 5.1, where full activity of actomyosin-ATPase is observed in the presence of the troponin--tropomyosin system. Assuming a rapid equilibrium between myosin light-chain kinase and two substrates, ATP and g2 light-chain, Km values for ATP and g2 light chain were evaluated as 0.28 mM and 0.024 mM, respectively. Vm/e was 5.7 s-1."} {"id": "PMID:153347", "title": "Effects of adenylyl imidodiphosphate, a nonhydrolyzable adenosine triphosphate analog, on reactivated and rigor wave sea urchin sperm.", "content": "A nonhydrolyzable ATP analog, adenylyl imidodiphosphate (AMP-PNP), has been used to study the role of ATP binding in flagellar motility. Sea urchin sperm of Lytechinus pictus were demembranated, reactivated, and locked in \"rigor waves\" by a modification of the method of Gibbons and Gibbons (11). Rigor wave sperm relaxed within 2 min after addition of 4 micrometer ATP, and reactivated upon addition of 10-12 micrometer ATP. The beat frequency of the reactivated sperm varied with ATP concentration according to Michaelis-Menten kinetics (\"Km\" = 0.24 mM; \"Vmax\" = 44 Hz) and was competitively inhibited by AMP-PNP (Ki\" approximately to 8.1 mM). Rigor wave sperm were completely relaxed (straightened) within 2 min by AMP-PNP at concentrations of 2-4 mM. The possibilities that relaxation in AMP-PNP was a result of ATP contamination, AMP-PNP hydrolysis, or lowering of the free Mg++ concentration were conclusively ruled out. The results suggest that dynein cross-bridge release is dependent upon ATP binding but not hydrolysis.", "contents": "Effects of adenylyl imidodiphosphate, a nonhydrolyzable adenosine triphosphate analog, on reactivated and rigor wave sea urchin sperm. A nonhydrolyzable ATP analog, adenylyl imidodiphosphate (AMP-PNP), has been used to study the role of ATP binding in flagellar motility. Sea urchin sperm of Lytechinus pictus were demembranated, reactivated, and locked in \"rigor waves\" by a modification of the method of Gibbons and Gibbons (11). Rigor wave sperm relaxed within 2 min after addition of 4 micrometer ATP, and reactivated upon addition of 10-12 micrometer ATP. The beat frequency of the reactivated sperm varied with ATP concentration according to Michaelis-Menten kinetics (\"Km\" = 0.24 mM; \"Vmax\" = 44 Hz) and was competitively inhibited by AMP-PNP (Ki\" approximately to 8.1 mM). Rigor wave sperm were completely relaxed (straightened) within 2 min by AMP-PNP at concentrations of 2-4 mM. The possibilities that relaxation in AMP-PNP was a result of ATP contamination, AMP-PNP hydrolysis, or lowering of the free Mg++ concentration were conclusively ruled out. The results suggest that dynein cross-bridge release is dependent upon ATP binding but not hydrolysis."} {"id": "PMID:153348", "title": "Reflex conditioning in a spinal man.", "content": "A man with a completely transected spinal cord and a spastic neurogenic bladder was conditioned to void upon the presentation of an external stimulus. A classical conditioning paradigm was employed in which strong abdominal shock (unconditioned stimulus) was paired with an initially neutral mild electrical stimulation of the thigh (conditioned stimulus; CS). After the pairing trials, a reliable conditioned response of urination was elicited by the CS alone. The conditioned response did not extinguish over time, and the procedure left the bladder with clinically safe residual amounts of urine. Practical implications of the conditioning technique for the treatment of spastic neurogenic bladder conditions in spinally injured patients are discussed, as is the theoretical significance of conditioning at the reflex level in the absence of cortical involvement.", "contents": "Reflex conditioning in a spinal man. A man with a completely transected spinal cord and a spastic neurogenic bladder was conditioned to void upon the presentation of an external stimulus. A classical conditioning paradigm was employed in which strong abdominal shock (unconditioned stimulus) was paired with an initially neutral mild electrical stimulation of the thigh (conditioned stimulus; CS). After the pairing trials, a reliable conditioned response of urination was elicited by the CS alone. The conditioned response did not extinguish over time, and the procedure left the bladder with clinically safe residual amounts of urine. Practical implications of the conditioning technique for the treatment of spastic neurogenic bladder conditions in spinally injured patients are discussed, as is the theoretical significance of conditioning at the reflex level in the absence of cortical involvement."} {"id": "PMID:153351", "title": "Huntington's disease: current concepts of therapy.", "content": "Huntington's disease (Huntington's chorea), a degenerative disorder of the central nervous system, is inherited in an autosomal dominant pattern. Since there is no cure for this genetic disorder, therapy has been focused on pharmacologic manipulation of the involved neurotransmitter systems. In Huntington's disease, there is a functional predominance of striatal dopaminergic activity over antagonist cholinergic and possibly GABA-minergic systems. Many dopaminergic antagonists and cholinergic and GABA-minergic agonists are currently used in treatment. Supportive psychiatric care for affected persons and their families is an important therapeutic adjunct in the management of Huntington's disease. The eventual therapy will depend upon accurate identification of the primary genetic defect.", "contents": "Huntington's disease: current concepts of therapy. Huntington's disease (Huntington's chorea), a degenerative disorder of the central nervous system, is inherited in an autosomal dominant pattern. Since there is no cure for this genetic disorder, therapy has been focused on pharmacologic manipulation of the involved neurotransmitter systems. In Huntington's disease, there is a functional predominance of striatal dopaminergic activity over antagonist cholinergic and possibly GABA-minergic systems. Many dopaminergic antagonists and cholinergic and GABA-minergic agonists are currently used in treatment. Supportive psychiatric care for affected persons and their families is an important therapeutic adjunct in the management of Huntington's disease. The eventual therapy will depend upon accurate identification of the primary genetic defect."} {"id": "PMID:153353", "title": "[Rabbit experimental glaucoma--preliminary study (author's transl)].", "content": "Induced high intraocular pressure, lasting more than one hour, is described in the rabbit. We inject simultaneously inside aqueous humor Epsilon Amino Caproic Acid 5 mg and Thrombin 20 U.S.N.I.H. units. To avoid leakage of aqueous humor we make the injection though a nou-perforating corneal preplaced loep and sight the suture to close the track when injection needle is taken out. We assume that high intraocular pressure is induced by 1% Adrenaline, 2% Pilocarpine and 1% Guanethidine solutions dropped in the eye each 5 mn, beginning 15 mn before anterior chamber injection and lasting during all the experiment. We point out this fact as a proof of the suitability of this method.", "contents": "[Rabbit experimental glaucoma--preliminary study (author's transl)]. Induced high intraocular pressure, lasting more than one hour, is described in the rabbit. We inject simultaneously inside aqueous humor Epsilon Amino Caproic Acid 5 mg and Thrombin 20 U.S.N.I.H. units. To avoid leakage of aqueous humor we make the injection though a nou-perforating corneal preplaced loep and sight the suture to close the track when injection needle is taken out. We assume that high intraocular pressure is induced by 1% Adrenaline, 2% Pilocarpine and 1% Guanethidine solutions dropped in the eye each 5 mn, beginning 15 mn before anterior chamber injection and lasting during all the experiment. We point out this fact as a proof of the suitability of this method."} {"id": "PMID:153354", "title": "[Thin soft hydrogel lenses of high and low water (author's transl)].", "content": "The authors relate the results obtained with very thin soft hydrogel lenses (0,10 mm thickness) of high and low water content: the Vergo-Softcon THX of 70% water-content and the Bauch and Lomb Plano-T of 38%. The most frequent indications encountered are bullous keratopathy, epithelial defects and keratitis sicca. The results are positive in 78,2% of cases with 70% w/c soft hydrogel lenses. Results are given for cases of direct fitting of thin lenses, as well as for cases of fitting after failures of classic soft hydrogel lenses and in cases of exchanges of 40% lenses for 70% lenses. The 70% water content lenses seem to give better results main in cases of epithelial defects and keratitis sicca.", "contents": "[Thin soft hydrogel lenses of high and low water (author's transl)]. The authors relate the results obtained with very thin soft hydrogel lenses (0,10 mm thickness) of high and low water content: the Vergo-Softcon THX of 70% water-content and the Bauch and Lomb Plano-T of 38%. The most frequent indications encountered are bullous keratopathy, epithelial defects and keratitis sicca. The results are positive in 78,2% of cases with 70% w/c soft hydrogel lenses. Results are given for cases of direct fitting of thin lenses, as well as for cases of fitting after failures of classic soft hydrogel lenses and in cases of exchanges of 40% lenses for 70% lenses. The 70% water content lenses seem to give better results main in cases of epithelial defects and keratitis sicca."} {"id": "PMID:153355", "title": "[Utility of soft hydrogel contact lenses in case of epithelial defects after corneal grafts (19) (author's transl)].", "content": "The authors relate the utility of soft hydrogel contact lenses in 19 cases of epithelial defects after penetrating corneal grafts, 8 of them being primitive and 11 secondary. Out of the 19 cases fitted with lenses, 10 have required a new keratoplasty. An attempt is made to define the indications, the advantages and the drawbacks of this therapy in observing the action of the lens on the epithelium, the stroma, the visual acuity as well as the possible problems due to the wearing of the lenses in the whole of the 19 cases. They try to understand the reasons for a new graft and they study the non-regrafted cases. They evidence the benefits of the wear of soft hydrogel lenses but the limits of their uses too.", "contents": "[Utility of soft hydrogel contact lenses in case of epithelial defects after corneal grafts (19) (author's transl)]. The authors relate the utility of soft hydrogel contact lenses in 19 cases of epithelial defects after penetrating corneal grafts, 8 of them being primitive and 11 secondary. Out of the 19 cases fitted with lenses, 10 have required a new keratoplasty. An attempt is made to define the indications, the advantages and the drawbacks of this therapy in observing the action of the lens on the epithelium, the stroma, the visual acuity as well as the possible problems due to the wearing of the lenses in the whole of the 19 cases. They try to understand the reasons for a new graft and they study the non-regrafted cases. They evidence the benefits of the wear of soft hydrogel lenses but the limits of their uses too."} {"id": "PMID:153356", "title": "[Prognosis of the retinal detachment in children (author's transl)].", "content": "Following features seem to characterize retinal detachments in children. High rate of difficult anatomical problems: invisible retinal breaks, macular or paramacular breaks, giant breaks or desinsertions (37% of our cases). High rate of severe traumatic macular lesions. Important delay in treatment with prolonged macular impairment. These facts explain the prognosis. Difficulties in the treatment of retinal breaks explain anatomical results (75% cure rate vs 78,6% for all the retinal detachments treated). In the same way they explain the high rate of multiple operations. Macular impairment and multiple operations explain visual results: 1/3 of the non amblyopic eyes recover a visual acuity comparable to the initial. So, the macular in children does not seem to have a special functional recuperation ability. Two supplementary facts may be mentioned. Delay in treatment has no adverse effect in anatomic prognosis. Non giant \"simple\" desinsertions expose to a noticeable risk of massive vitreous retraction.", "contents": "[Prognosis of the retinal detachment in children (author's transl)]. Following features seem to characterize retinal detachments in children. High rate of difficult anatomical problems: invisible retinal breaks, macular or paramacular breaks, giant breaks or desinsertions (37% of our cases). High rate of severe traumatic macular lesions. Important delay in treatment with prolonged macular impairment. These facts explain the prognosis. Difficulties in the treatment of retinal breaks explain anatomical results (75% cure rate vs 78,6% for all the retinal detachments treated). In the same way they explain the high rate of multiple operations. Macular impairment and multiple operations explain visual results: 1/3 of the non amblyopic eyes recover a visual acuity comparable to the initial. So, the macular in children does not seem to have a special functional recuperation ability. Two supplementary facts may be mentioned. Delay in treatment has no adverse effect in anatomic prognosis. Non giant \"simple\" desinsertions expose to a noticeable risk of massive vitreous retraction."} {"id": "PMID:153357", "title": "[Astigmatism and corneal incision in cataract surgery. Statistical deductions (author's transl)].", "content": "Corneal incision in cataract surgery will produce a large degree of astigmatism greater than that produced in cataracts operated on by the classical methods. The position of the incision and the suture material (nylon) are responsible. The authors have attempted a statistical study of this difference, comparing modern and classical methods, referring for the latter to previous work.", "contents": "[Astigmatism and corneal incision in cataract surgery. Statistical deductions (author's transl)]. Corneal incision in cataract surgery will produce a large degree of astigmatism greater than that produced in cataracts operated on by the classical methods. The position of the incision and the suture material (nylon) are responsible. The authors have attempted a statistical study of this difference, comparing modern and classical methods, referring for the latter to previous work."} {"id": "PMID:153358", "title": "[Prevention of malignant glaucoma: pars-plana vitrectomy? (author's transl)].", "content": "Prevention of malignant glaucoma: in first case report lens extraction and trabeculectomy was followed by a malignant glaucoma; in the second case report pars-plana vitrectomy and trabeculectomy was successful. The role of a vitreous posterior blockage is discussed.", "contents": "[Prevention of malignant glaucoma: pars-plana vitrectomy? (author's transl)]. Prevention of malignant glaucoma: in first case report lens extraction and trabeculectomy was followed by a malignant glaucoma; in the second case report pars-plana vitrectomy and trabeculectomy was successful. The role of a vitreous posterior blockage is discussed."} {"id": "PMID:153359", "title": "[Types of occlusion in the treatment of convergent strabismus].", "content": "The different kinds of penalizations which are used in strabismus therapy--occlusion, atropine penalization, optic penalization, filters, partial occlusion of the glasses (sectors)--are being discussed with their advantages and disadvantages. Their indications and their results are reported according to the age of the child and the degree of the amblyopia.", "contents": "[Types of occlusion in the treatment of convergent strabismus]. The different kinds of penalizations which are used in strabismus therapy--occlusion, atropine penalization, optic penalization, filters, partial occlusion of the glasses (sectors)--are being discussed with their advantages and disadvantages. Their indications and their results are reported according to the age of the child and the degree of the amblyopia."} {"id": "PMID:153363", "title": "Synchronous growth and aging of Caenorhabditis elegans in the presence of fluorodeoxyuridine.", "content": "Fluorodeoxyuridine (FUdR), an inhibitor of DNA synthesis, was examined for its ability to prevent a synchronous population of C. elegans from reproducing without otherwise interfering with the organism's post-maturational development and aging. When a synchronized population was exposed to 400 micrometer FUdR just as the population reached sexual maturity, the FUdR induced complete sterility within five hours by preventing eggs from hatching. Any larvae that hatched from eggs made before the FUdR was added remained small in the presence of FUdR and were easily removed by filtration or sedimentation. FUdR-sterilized adults showed no morphological abnormalities. Age-associated changes seen in controls also occurred in FUdR-treated worms, including atrophy of the gonads, increased pigmentation, sluggishness and increased transparency. Life span was not shortened by FUdR treatment. Our observations suggest that treatment with FUdR under carefully controlled conditions is a reasonable way to maintain synchronously aging populations of C. elegans.", "contents": "Synchronous growth and aging of Caenorhabditis elegans in the presence of fluorodeoxyuridine. Fluorodeoxyuridine (FUdR), an inhibitor of DNA synthesis, was examined for its ability to prevent a synchronous population of C. elegans from reproducing without otherwise interfering with the organism's post-maturational development and aging. When a synchronized population was exposed to 400 micrometer FUdR just as the population reached sexual maturity, the FUdR induced complete sterility within five hours by preventing eggs from hatching. Any larvae that hatched from eggs made before the FUdR was added remained small in the presence of FUdR and were easily removed by filtration or sedimentation. FUdR-sterilized adults showed no morphological abnormalities. Age-associated changes seen in controls also occurred in FUdR-treated worms, including atrophy of the gonads, increased pigmentation, sluggishness and increased transparency. Life span was not shortened by FUdR treatment. Our observations suggest that treatment with FUdR under carefully controlled conditions is a reasonable way to maintain synchronously aging populations of C. elegans."} {"id": "PMID:153369", "title": "A weak human MLR locus mapping at the right of a crossing-over between HLA-D, Bf and GLO.", "content": "An unexpected MLR reaction has been observed between three HLA-identical sibs; it consists of bidirectional positive MLR between identical female twins and a sister. No argument for a lymphoid mosaic could be found, although twins were frequent in the family; similarly no HLA-A/B or HLA-B/D recombinant could be demonstrated. The MLR, although weak, was highly reproducible. PLTs could be raised between the sibs, without an apparent segregation in this family nor in five other families, but such PLTs discriminated well between the positive and negative controls. In the absence of any proof that such a weak MLR locus could be on another chromosome than chromosome 6, two lines of argument are indirect evidences that such a locus could be indeed on chromosome 6: one of the sibs differs from the two others for two markers outside HLA--D--DR--Bf: glyoxalate (GLO) and red blood group P.", "contents": "A weak human MLR locus mapping at the right of a crossing-over between HLA-D, Bf and GLO. An unexpected MLR reaction has been observed between three HLA-identical sibs; it consists of bidirectional positive MLR between identical female twins and a sister. No argument for a lymphoid mosaic could be found, although twins were frequent in the family; similarly no HLA-A/B or HLA-B/D recombinant could be demonstrated. The MLR, although weak, was highly reproducible. PLTs could be raised between the sibs, without an apparent segregation in this family nor in five other families, but such PLTs discriminated well between the positive and negative controls. In the absence of any proof that such a weak MLR locus could be on another chromosome than chromosome 6, two lines of argument are indirect evidences that such a locus could be indeed on chromosome 6: one of the sibs differs from the two others for two markers outside HLA--D--DR--Bf: glyoxalate (GLO) and red blood group P."} {"id": "PMID:153372", "title": "The electrocardiogram in ambulatory medical practice.", "content": "The electrocardiogram is one of medicine's most frequently ordered procedures. A review of the current use of electrocardiograms in ambulatory clinical practice and the possible information that might be supplied by an electrocardiogram was undertaken. The electrocardiogram's advantages and disadvantages when used in evaluating specific cardiac disorders are discussed including the use of the electrocardiogram as a baseline. Both their values and their limitations in diagnosis and management are examined to support the authors' conclusion that electrocardiograms should be used as an adjunct to clinical diagnosis, not as a screening procedure.", "contents": "The electrocardiogram in ambulatory medical practice. The electrocardiogram is one of medicine's most frequently ordered procedures. A review of the current use of electrocardiograms in ambulatory clinical practice and the possible information that might be supplied by an electrocardiogram was undertaken. The electrocardiogram's advantages and disadvantages when used in evaluating specific cardiac disorders are discussed including the use of the electrocardiogram as a baseline. Both their values and their limitations in diagnosis and management are examined to support the authors' conclusion that electrocardiograms should be used as an adjunct to clinical diagnosis, not as a screening procedure."} {"id": "PMID:153383", "title": "Myotonia in centronuclear myopathy.", "content": "Centronuclear myopathy, which is unusual because of clinical myotonia, is described in two sisters. The diagnosis was established in adult life, but the first symptoms were noticed in infancy. The outstanding points of the clinical picture were mild amyotrophy, paresis, and clinical myotonia.", "contents": "Myotonia in centronuclear myopathy. Centronuclear myopathy, which is unusual because of clinical myotonia, is described in two sisters. The diagnosis was established in adult life, but the first symptoms were noticed in infancy. The outstanding points of the clinical picture were mild amyotrophy, paresis, and clinical myotonia."} {"id": "PMID:153384", "title": "2-dimethylaminoethanol (Deanol) in Huntington's chorea.", "content": "A double-blind crossover trial with 2-dimethylaminoethanol (Deanol), a possible precursor of brain acetylcholine, was carried out in nine patients with Huntington's chorea. It was found to be ineffective in inducing any alteration in hyperkinesia.", "contents": "2-dimethylaminoethanol (Deanol) in Huntington's chorea. A double-blind crossover trial with 2-dimethylaminoethanol (Deanol), a possible precursor of brain acetylcholine, was carried out in nine patients with Huntington's chorea. It was found to be ineffective in inducing any alteration in hyperkinesia."} {"id": "PMID:153385", "title": "The early effects of ischemia upon skeletal muscle mitochondria.", "content": "The effects of early ischemia were studied in the anterior tibial muscle of Sprague-Dawley rats after 2--24 hr of tourniquet compression at the thigh. Ragged-red fibers, moth-eaten fibers, cores and targets were seen in tissue examined by enzyme histochemistry and electron microscopy. Giant mitochondria, abnormalities of cristal arrangement, crystalloids, osmiophilic inclusion bodies and myeloid figures were dominant features of the mitochondrial reaction. The results of this experiment indicate that early ischemia induces a variety of changes described in other neuromuscular conditions such as dystrophy and the \"mitochondrial myopathies\". The pathogenesis of these changes and their relationship to human disease of muscle is discussed.", "contents": "The early effects of ischemia upon skeletal muscle mitochondria. The effects of early ischemia were studied in the anterior tibial muscle of Sprague-Dawley rats after 2--24 hr of tourniquet compression at the thigh. Ragged-red fibers, moth-eaten fibers, cores and targets were seen in tissue examined by enzyme histochemistry and electron microscopy. Giant mitochondria, abnormalities of cristal arrangement, crystalloids, osmiophilic inclusion bodies and myeloid figures were dominant features of the mitochondrial reaction. The results of this experiment indicate that early ischemia induces a variety of changes described in other neuromuscular conditions such as dystrophy and the \"mitochondrial myopathies\". The pathogenesis of these changes and their relationship to human disease of muscle is discussed."} {"id": "PMID:153386", "title": "Receptor potential and spike initiation in two varieties of snake muscle spindles.", "content": "1. Receptor potentials, in response to ramp-and-hold stretch, have been recorded from two varieties of snake muscle spindles. 2. The two types of spindles have a similar sensitivity of impulse discharge to amplitude of receptor potential during the static phase of stretch. 3. Receptor potentials from short-capsule spindles show a high dynamic sensitivity to velocity of stretch. Amplitude of dynamic receptor potentials is well related to frequency of dynamic discharge except beyond a certain velocity of stretch where the frequency deviates progressively more than expected from linearity. 4. Receptor potentials from long-capsule spindles show a low dynamic sensitivity to velocity of stretch and amplitude of dynamic receptor potentials is well correlated with dynamic firing frequency. 5. The threshold level of receptor potential for initiating spike discharge varies with the velocity of stretch, the relation being similar for the two types of spindles. 6. It is concluded that the basis for functional differentiation of snake spindles may lie in the mechanism by which deformation of sensory endings is transformed into receptor potential. 7. Late adaptation of impulse discharge, a characteristic feature of the response of the short-capsule spindle to maintained stretch, has been related to length changes of the sensory region measured directly with Nomarski optics. The linear relation found between the slow adaptive fall of impulse discharge and the simultaneous shortening of the sensory region strongly suggests a mechanical basis for the late adaptation.", "contents": "Receptor potential and spike initiation in two varieties of snake muscle spindles. 1. Receptor potentials, in response to ramp-and-hold stretch, have been recorded from two varieties of snake muscle spindles. 2. The two types of spindles have a similar sensitivity of impulse discharge to amplitude of receptor potential during the static phase of stretch. 3. Receptor potentials from short-capsule spindles show a high dynamic sensitivity to velocity of stretch. Amplitude of dynamic receptor potentials is well related to frequency of dynamic discharge except beyond a certain velocity of stretch where the frequency deviates progressively more than expected from linearity. 4. Receptor potentials from long-capsule spindles show a low dynamic sensitivity to velocity of stretch and amplitude of dynamic receptor potentials is well correlated with dynamic firing frequency. 5. The threshold level of receptor potential for initiating spike discharge varies with the velocity of stretch, the relation being similar for the two types of spindles. 6. It is concluded that the basis for functional differentiation of snake spindles may lie in the mechanism by which deformation of sensory endings is transformed into receptor potential. 7. Late adaptation of impulse discharge, a characteristic feature of the response of the short-capsule spindle to maintained stretch, has been related to length changes of the sensory region measured directly with Nomarski optics. The linear relation found between the slow adaptive fall of impulse discharge and the simultaneous shortening of the sensory region strongly suggests a mechanical basis for the late adaptation."} {"id": "PMID:153387", "title": "Potential hearing compensation cost by race and sex.", "content": "A large general industrial population (n = 10,000) is analyzed using different low fences (15 bB HTL to 35 dB HTL) with the high fence held constant at 93 dB HTL. Three different audiometric test frequency combinations are considered: HTL.5,1,2 kHz, HTL.5,1,2,3 kHz and HTL1,2,3 kHz. The data base is analyzed first as a total population and then divided into different subpopulations including male, female, black and whites; and further subdivided into black males, black females, white males and white females. The findings indicate that significant differences exist between the groupings with respect to the potential hearing compensation cost and percent of a population exceeding the different low fence frequency combinations.", "contents": "Potential hearing compensation cost by race and sex. A large general industrial population (n = 10,000) is analyzed using different low fences (15 bB HTL to 35 dB HTL) with the high fence held constant at 93 dB HTL. Three different audiometric test frequency combinations are considered: HTL.5,1,2 kHz, HTL.5,1,2,3 kHz and HTL1,2,3 kHz. The data base is analyzed first as a total population and then divided into different subpopulations including male, female, black and whites; and further subdivided into black males, black females, white males and white females. The findings indicate that significant differences exist between the groupings with respect to the potential hearing compensation cost and percent of a population exceeding the different low fence frequency combinations."} {"id": "PMID:153403", "title": "Assessment of standing aids for the physically handicapped.", "content": "The suitability of four commercially available standing aids was assessed for routine therapy of a group of severely handicapped patients in hospital care. The problems which arose were mainly technical and these are considered. From experience gained during the study the design requirements of an ideal aid for these patients are proposed.", "contents": "Assessment of standing aids for the physically handicapped. The suitability of four commercially available standing aids was assessed for routine therapy of a group of severely handicapped patients in hospital care. The problems which arose were mainly technical and these are considered. From experience gained during the study the design requirements of an ideal aid for these patients are proposed."} {"id": "PMID:153404", "title": "Medicine and disability--a broader view.", "content": "This paper seeks to emphasise the social approach in the treatment of disability. It is important that disabled people should lead as near a normal life as possible with some financial security. Financial assistance for disabled people is left up to individual local authorities. The author points out the disadvantages of this system and draws attention to a voluntary organisation which fills a gap in existing services.", "contents": "Medicine and disability--a broader view. This paper seeks to emphasise the social approach in the treatment of disability. It is important that disabled people should lead as near a normal life as possible with some financial security. Financial assistance for disabled people is left up to individual local authorities. The author points out the disadvantages of this system and draws attention to a voluntary organisation which fills a gap in existing services."} {"id": "PMID:153405", "title": "Reversal of the calcium pump in human red cells.", "content": "Human red cells containing low ATP and high Pi concentrations were suspended in media with and without 2 mM Ca2+, and the incorporation of (32P)Pi into ATP was measured. There was some incorporation whatever the medium, but in every experiment there was an extra incorporation when the cells were in the Ca2+-containing medium. This extra incorporation was abolished by the ionophore A23187, which collapses the Ca2+ concentration gradient across the membranes, or by LaCl3, which blocks the Ca2+ pump. Starved and phosphate-loaded cells also show an uptake of Ca2+ which is not apparent in fresh cells. Results are consistent with the idea that Ca2+-dependent incorporation of Pi into ATP is catalyzed by the Ca2+ pump using energy derived from the Ca2+ concentration gradient.", "contents": "Reversal of the calcium pump in human red cells. Human red cells containing low ATP and high Pi concentrations were suspended in media with and without 2 mM Ca2+, and the incorporation of (32P)Pi into ATP was measured. There was some incorporation whatever the medium, but in every experiment there was an extra incorporation when the cells were in the Ca2+-containing medium. This extra incorporation was abolished by the ionophore A23187, which collapses the Ca2+ concentration gradient across the membranes, or by LaCl3, which blocks the Ca2+ pump. Starved and phosphate-loaded cells also show an uptake of Ca2+ which is not apparent in fresh cells. Results are consistent with the idea that Ca2+-dependent incorporation of Pi into ATP is catalyzed by the Ca2+ pump using energy derived from the Ca2+ concentration gradient."} {"id": "PMID:153407", "title": "Demonstration of antibody activity to clioquinol in sera of experimental rabbits and patients with subacute myelo-optico-neuropathy.", "content": "Antibody to clioquinol(5-chloro-7-iodo-8-hydroxyquinoline:CIHQ) was detected by passive hemagglutinating reaction in rabbits receiving a prolonged administration of Emaform which was once a commercial preparation of CIHQ. The antibody was shown to be in the immunoglobulin fractions by separation with a specific immunoadsorbent, and it had relatively broad antigenic specificity. The antibody was also demonstrated in sera from patients who suffered from Subacute Myelo-Optico-Neuropathy (SMON) and from normal healthy individuals. However, its titer and frequency of positive reactors in the former were higher than those in the latter, and the two groups could be differentiated each other in frequency distribution patterns of the antibody proprietors. From these results, we discussed on desirable application of sero-epidemiological study to assessment of effects of chemical pollutants on living systems.", "contents": "Demonstration of antibody activity to clioquinol in sera of experimental rabbits and patients with subacute myelo-optico-neuropathy. Antibody to clioquinol(5-chloro-7-iodo-8-hydroxyquinoline:CIHQ) was detected by passive hemagglutinating reaction in rabbits receiving a prolonged administration of Emaform which was once a commercial preparation of CIHQ. The antibody was shown to be in the immunoglobulin fractions by separation with a specific immunoadsorbent, and it had relatively broad antigenic specificity. The antibody was also demonstrated in sera from patients who suffered from Subacute Myelo-Optico-Neuropathy (SMON) and from normal healthy individuals. However, its titer and frequency of positive reactors in the former were higher than those in the latter, and the two groups could be differentiated each other in frequency distribution patterns of the antibody proprietors. From these results, we discussed on desirable application of sero-epidemiological study to assessment of effects of chemical pollutants on living systems."} {"id": "PMID:153408", "title": "The role of trauma in low back pain: a review.", "content": "Trauma plays an important role in the production of low back pain. This review emphasizes how the forces to which the spine is subjected are modified by many factors. Attention is directed to the role of mechanical stress in the etiology of spondylolisthesis, subtle spinal fractures, as well as the relevance of stress to the degenerative process. It is suggested that trauma plays a very major role in low back pain but, at present, the problems in diagnostic technology create difficulty in establishing the precise degree of that role. The drawbacks of over-reliance on plane radiography are emphasized. It is suggested that improved diagnostic techniques may result in more accurate treatment and perhaps less disability resultant from the ubiquitous problem of low back pain.", "contents": "The role of trauma in low back pain: a review. Trauma plays an important role in the production of low back pain. This review emphasizes how the forces to which the spine is subjected are modified by many factors. Attention is directed to the role of mechanical stress in the etiology of spondylolisthesis, subtle spinal fractures, as well as the relevance of stress to the degenerative process. It is suggested that trauma plays a very major role in low back pain but, at present, the problems in diagnostic technology create difficulty in establishing the precise degree of that role. The drawbacks of over-reliance on plane radiography are emphasized. It is suggested that improved diagnostic techniques may result in more accurate treatment and perhaps less disability resultant from the ubiquitous problem of low back pain."} {"id": "PMID:153409", "title": "Production and expression of dTMP-enriched DNA of bacteriophage SP15.", "content": "Normal DNA of Bacillus subtilis phage SP15 contains approximately equimolar quantities of dTMP and a hypermodified nucleotide, 5-dihydroxypentyl-dUMP (DHPdUMP). Deoxythymidine (dThd) rescue of phage DNA synthesis in 5-fluorodeoxyuridine (FUdR)-inhibited cultures resulted in the synthesis of SP15 DNA containing enhanced levels of dTMP and correspondingly reduced levels of DHPdUMP. This rescued system was used to probe possible roles of DHPdUMP in phage development. The results suggested that normal levels of DHPdUMP were not required for proper transcription of phage DNA, but normal amounts of DHPdUMP were indispensable for phage assembly and/or DNA maturation. The amount of exogenous dThd required to rescue phage DNA synthesis in FUdR-inhibited cultures was 20-fold higher than the concentration required to rescue cellular replication, whereas the same low concentrations of dThd sufficed to rescue viral and bacterial DNA syntheses in aminopterin-inhibited cultures. Normal SP15 DNA was made in rescued, aminopterin-inhibited cultures. We suggest that FUdR (but not aminopterin) partially suppresses biosynthesis of the hypermodified nucleotide and that there is a barrier to replacement of DHPdUMP by dTMP; therefore, exceptionally large amounts of dThd must be salvaged in FUdR-inhibited cultures to force replacement of the unusual nucleotide by dTMP.", "contents": "Production and expression of dTMP-enriched DNA of bacteriophage SP15. Normal DNA of Bacillus subtilis phage SP15 contains approximately equimolar quantities of dTMP and a hypermodified nucleotide, 5-dihydroxypentyl-dUMP (DHPdUMP). Deoxythymidine (dThd) rescue of phage DNA synthesis in 5-fluorodeoxyuridine (FUdR)-inhibited cultures resulted in the synthesis of SP15 DNA containing enhanced levels of dTMP and correspondingly reduced levels of DHPdUMP. This rescued system was used to probe possible roles of DHPdUMP in phage development. The results suggested that normal levels of DHPdUMP were not required for proper transcription of phage DNA, but normal amounts of DHPdUMP were indispensable for phage assembly and/or DNA maturation. The amount of exogenous dThd required to rescue phage DNA synthesis in FUdR-inhibited cultures was 20-fold higher than the concentration required to rescue cellular replication, whereas the same low concentrations of dThd sufficed to rescue viral and bacterial DNA syntheses in aminopterin-inhibited cultures. Normal SP15 DNA was made in rescued, aminopterin-inhibited cultures. We suggest that FUdR (but not aminopterin) partially suppresses biosynthesis of the hypermodified nucleotide and that there is a barrier to replacement of DHPdUMP by dTMP; therefore, exceptionally large amounts of dThd must be salvaged in FUdR-inhibited cultures to force replacement of the unusual nucleotide by dTMP."} {"id": "PMID:153410", "title": "Use of vascular prosthesis in the anastomosis of allograft renal artery.", "content": "A case is reported in which a cadaveric renal allograft was placed successfully in a patient with a bilateral aortofemoral prosthesis for extensive vascular disease. Convalescence was uneventful and the subsequent clinical course seems to justify fully this operative approach.", "contents": "Use of vascular prosthesis in the anastomosis of allograft renal artery. A case is reported in which a cadaveric renal allograft was placed successfully in a patient with a bilateral aortofemoral prosthesis for extensive vascular disease. Convalescence was uneventful and the subsequent clinical course seems to justify fully this operative approach."} {"id": "PMID:153406", "title": "Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa.", "content": "Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in N. crassa. Genetic analysis of the mutants indicated that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the mono-functional alkylating agents ethyleneimine (EI), ethylmethanesulfonate (EMS), and ICR-177. It is therefore suggested that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.", "contents": "Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa. Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in N. crassa. Genetic analysis of the mutants indicated that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the mono-functional alkylating agents ethyleneimine (EI), ethylmethanesulfonate (EMS), and ICR-177. It is therefore suggested that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents."} {"id": "PMID:153412", "title": "Chromosomal aberrations and congenital heart diseases.", "content": "The incidence of chromosomal aberration with CHD is 10.5% in the autopsy cases. 2. The characteristic major cardiac malformations associated with chromosomal aberration are conal abnormality, abnormal septation and cardiac valve abnormalities. 3. The characteristic association of chromosomal aberration and CHD is CAVO in Down syndrome, triple shunts and multivalvular disease in 18 trisomy, shunts in delition syndrome and coarctation of the aorta in Turner syndrome. 4. Minor cardiac anomalies associated with chromosomal aberration are valve dysplasia such as bicuspid semilunar cusps, parachute A-V valve, thickning, deformity and insufficient differentiation of valve and of chordae tendinae and hypoplastic or immature papillary muscles. 5. Primary target in cardiovascular involvement by chromosomal aberration might be a cement property of the connective tissue which is expected to conseal the foramens and shunts and to develop valve structures in embryonic heart.", "contents": "Chromosomal aberrations and congenital heart diseases. The incidence of chromosomal aberration with CHD is 10.5% in the autopsy cases. 2. The characteristic major cardiac malformations associated with chromosomal aberration are conal abnormality, abnormal septation and cardiac valve abnormalities. 3. The characteristic association of chromosomal aberration and CHD is CAVO in Down syndrome, triple shunts and multivalvular disease in 18 trisomy, shunts in delition syndrome and coarctation of the aorta in Turner syndrome. 4. Minor cardiac anomalies associated with chromosomal aberration are valve dysplasia such as bicuspid semilunar cusps, parachute A-V valve, thickning, deformity and insufficient differentiation of valve and of chordae tendinae and hypoplastic or immature papillary muscles. 5. Primary target in cardiovascular involvement by chromosomal aberration might be a cement property of the connective tissue which is expected to conseal the foramens and shunts and to develop valve structures in embryonic heart."} {"id": "PMID:153423", "title": "[Neuronal and extraneuronal noradrenaline uptake and the state of the adrenoreactive structures of the isolated rat heart with compensatory myocardial hypertrophy].", "content": "It was demonstrated on an isolated heart preparation that the intensity of neuronal noradrenaline uptake by a hypertrophied heart diminishes as compared to that by a control in 6 and 30 days after constriction of the abdominal aorta and that extraneuronal uptake tends to intensify in 6 days and decreases significantly in 30 days. These changes, together with the reduced adrenoreactivity of a hypertrophied heart in vitro may in 30 days contribute to weakening of the adrenergic control of the heart in its compensatory hypertrophy and hyperfunction under conditions of chronic overloading by pressure.", "contents": "[Neuronal and extraneuronal noradrenaline uptake and the state of the adrenoreactive structures of the isolated rat heart with compensatory myocardial hypertrophy]. It was demonstrated on an isolated heart preparation that the intensity of neuronal noradrenaline uptake by a hypertrophied heart diminishes as compared to that by a control in 6 and 30 days after constriction of the abdominal aorta and that extraneuronal uptake tends to intensify in 6 days and decreases significantly in 30 days. These changes, together with the reduced adrenoreactivity of a hypertrophied heart in vitro may in 30 days contribute to weakening of the adrenergic control of the heart in its compensatory hypertrophy and hyperfunction under conditions of chronic overloading by pressure."} {"id": "PMID:153427", "title": "[Herpetiform bilateral epithelial corneal dystrophy caused by Tyrosinemia (Richner-Hanhart-Syndrome) (author's transl)].", "content": "Nutritional Tyrosinemia in animal experiments (Schweizer, Burns a. o.) caused an epithelial corneal dystrophy. The corresponding clinical picture is the Richner-Hanhart-Syndrome with herpetiform epithelial corneal dystrophy, palmo-plantar-keratosis and -- in some case -- a later developing oligophrenia. Goldsmith and coworkers suceeded to find out that all these symptoms are combined with tyrosinemia presumably caused ty one congenital enzyme defect. -- Personal clinical observations of such patients demonstrate that as well the corneal as the dermatological symptoms could be cured by diet, if the diagnosis is made in childhood. Corneal symptoms are still absent with a tyrosinemia as high as 10 mg%. Dietetic formula was found out to maintain this level, which is low enough to avoid the symptoms of Richner-Hanhart-Syndrome and certainly high enough to avoid symptoms of nutritional deficiency. One might expect that oligophrenia will not develop if this diet is used consequently. -- Since the first corneal symptoms develop already during the first years of life the ophthalmologist ought to know this etiology. The levels of tyrosinemia are so exorbitant (30--50 mg%) that the laboratory diagnosis is possible without any difficulty. If the diagnosis is only made in adult patients dietetic therapy is of limited value.", "contents": "[Herpetiform bilateral epithelial corneal dystrophy caused by Tyrosinemia (Richner-Hanhart-Syndrome) (author's transl)]. Nutritional Tyrosinemia in animal experiments (Schweizer, Burns a. o.) caused an epithelial corneal dystrophy. The corresponding clinical picture is the Richner-Hanhart-Syndrome with herpetiform epithelial corneal dystrophy, palmo-plantar-keratosis and -- in some case -- a later developing oligophrenia. Goldsmith and coworkers suceeded to find out that all these symptoms are combined with tyrosinemia presumably caused ty one congenital enzyme defect. -- Personal clinical observations of such patients demonstrate that as well the corneal as the dermatological symptoms could be cured by diet, if the diagnosis is made in childhood. Corneal symptoms are still absent with a tyrosinemia as high as 10 mg%. Dietetic formula was found out to maintain this level, which is low enough to avoid the symptoms of Richner-Hanhart-Syndrome and certainly high enough to avoid symptoms of nutritional deficiency. One might expect that oligophrenia will not develop if this diet is used consequently. -- Since the first corneal symptoms develop already during the first years of life the ophthalmologist ought to know this etiology. The levels of tyrosinemia are so exorbitant (30--50 mg%) that the laboratory diagnosis is possible without any difficulty. If the diagnosis is only made in adult patients dietetic therapy is of limited value."} {"id": "PMID:153428", "title": "[Immune defect syndrome in Crohn's disease (author's transl)].", "content": "In 20 patients suffering for several years from serious chronic relapsing Crohn's disease the following immunological tests were carried out: (1) in-vitro stimulation of blood lymphocytes by PHA-P, (2) identification of T and B cells by formation of spontaneous rosettes and complement receptor rosettes, (3) effect of Crohn's serum on mixed lymphocyte reaction (MLR) of normal allogeneic lymphocytes, (4) in-vitro phagocytosis and intracellular killing of E. coli by polymorphonuclear granulocytes. The results indicate an immune defect of lymphocyte function and the effect of humoral factor(s) on T cell mediated immune reactions: (1) Lymphocyte stimulation by PHA-P was reduced significantly in Crohn's disease. In PHA-P dose response, maximal stimulation has shown a decrease and a shift to higher doses. (2) An increase in the absolute number of B cells caused a decrease in the mean percentage of T cells. The absolute number of T cells did not differ significantly from those of the controls. (3) Crohn's serum has shown an inhibitory effect in MLR of normal lymphocytes. (4) No impairment of phagocytosis or intracellular killing by polymorphonuclear granulocytes has been observed. The results suggest a symptomatic immune defect syndrome in a wasting disease. There is no evidence of a primary immune defect in Crohn's disease.", "contents": "[Immune defect syndrome in Crohn's disease (author's transl)]. In 20 patients suffering for several years from serious chronic relapsing Crohn's disease the following immunological tests were carried out: (1) in-vitro stimulation of blood lymphocytes by PHA-P, (2) identification of T and B cells by formation of spontaneous rosettes and complement receptor rosettes, (3) effect of Crohn's serum on mixed lymphocyte reaction (MLR) of normal allogeneic lymphocytes, (4) in-vitro phagocytosis and intracellular killing of E. coli by polymorphonuclear granulocytes. The results indicate an immune defect of lymphocyte function and the effect of humoral factor(s) on T cell mediated immune reactions: (1) Lymphocyte stimulation by PHA-P was reduced significantly in Crohn's disease. In PHA-P dose response, maximal stimulation has shown a decrease and a shift to higher doses. (2) An increase in the absolute number of B cells caused a decrease in the mean percentage of T cells. The absolute number of T cells did not differ significantly from those of the controls. (3) Crohn's serum has shown an inhibitory effect in MLR of normal lymphocytes. (4) No impairment of phagocytosis or intracellular killing by polymorphonuclear granulocytes has been observed. The results suggest a symptomatic immune defect syndrome in a wasting disease. There is no evidence of a primary immune defect in Crohn's disease."} {"id": "PMID:153429", "title": "Colonization resistance of the digestive tract and gastrointestinal transit time in SPF mice.", "content": "The gastro-intestinal colonization resistance to Escherichia coli was assessed in individual CBA/Rij, C3H/StZ and Swiss/Cpb:SE mice. Gastro-intestinal transit time was determined by feeding small steel balls and x-ray examination of sequentially collected faeces. No correlation was found between transit times measured on 3 subsequent days, nor between them and colonization resistance.", "contents": "Colonization resistance of the digestive tract and gastrointestinal transit time in SPF mice. The gastro-intestinal colonization resistance to Escherichia coli was assessed in individual CBA/Rij, C3H/StZ and Swiss/Cpb:SE mice. Gastro-intestinal transit time was determined by feeding small steel balls and x-ray examination of sequentially collected faeces. No correlation was found between transit times measured on 3 subsequent days, nor between them and colonization resistance."} {"id": "PMID:153431", "title": "Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity.", "content": "Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease.", "contents": "Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity. Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease."} {"id": "PMID:153432", "title": "Ultrastructure of the fibrous subaortic \"ring\" in dogs with discrete subaortic stenosis.", "content": "The subaortic fibrous \"ring\" in Newfoundland dogs with discrete subaortic stenosis is characterized by the presence of large, uni- and multinucleated, rounded connective tissue cells that resemble chondrocytes in several respects. Connective tissue adjacent to these cells is rich in acid mucopolysaccharides, small but cross-banded collagen fibrils, and small, poorly developed elastic fibers. The chondrocyte-like cells contain numerous cisternae of rough surfaced endoplasmic reticulum and prominent Golgi complexes, and they are surrounded by thick, concentrically arranged layers of basement membrane-like material. The differentiation of cellular and extracellular components of connective tissue in subaortic fibrous rings clearly differs in humans and in dogs with discrete subaortic stenosis.", "contents": "Ultrastructure of the fibrous subaortic \"ring\" in dogs with discrete subaortic stenosis. The subaortic fibrous \"ring\" in Newfoundland dogs with discrete subaortic stenosis is characterized by the presence of large, uni- and multinucleated, rounded connective tissue cells that resemble chondrocytes in several respects. Connective tissue adjacent to these cells is rich in acid mucopolysaccharides, small but cross-banded collagen fibrils, and small, poorly developed elastic fibers. The chondrocyte-like cells contain numerous cisternae of rough surfaced endoplasmic reticulum and prominent Golgi complexes, and they are surrounded by thick, concentrically arranged layers of basement membrane-like material. The differentiation of cellular and extracellular components of connective tissue in subaortic fibrous rings clearly differs in humans and in dogs with discrete subaortic stenosis."} {"id": "PMID:153435", "title": "Visual reinforcement audiometry (VRA) with young Down's syndrome children.", "content": "Visual Reinforcement Audiometry (VRA) was investigated with 41 Down's syndrome subjects between the ages of six months and six years. The VRA procedure involved monitoring a head-turn response to a complex noise signal presented in a sound field with an ascending presentation paradigm and reinforced by a complex visual reinforcer. Twenty-four of the infants and young children also were evaluated with the Bayley Scales of Infant Development (BSID) to allow for analysis of the efficacy of VRA as a function of developmental age. Results were as follows: (1) 28 (68%) of the infants and young children initially oriented towards the source of the auditory stimulus, (2) only a few of the subjects who did not initially orient could be taught to respond, (3) of the children who initially oriented or were taught to respond, thresholds were obtained on a large number (81%) in one visit, and (4) a systematic relationship was demonstrated between consistency of subject response using the VRA technique and BSID Mental Age Equivalent with 10 months being the critical age for determining the potential success of the procedure. In addition, the results implied a higher incidence of hearing loss in the Down's syndrome subjects than found in normal pediatric population.", "contents": "Visual reinforcement audiometry (VRA) with young Down's syndrome children. Visual Reinforcement Audiometry (VRA) was investigated with 41 Down's syndrome subjects between the ages of six months and six years. The VRA procedure involved monitoring a head-turn response to a complex noise signal presented in a sound field with an ascending presentation paradigm and reinforced by a complex visual reinforcer. Twenty-four of the infants and young children also were evaluated with the Bayley Scales of Infant Development (BSID) to allow for analysis of the efficacy of VRA as a function of developmental age. Results were as follows: (1) 28 (68%) of the infants and young children initially oriented towards the source of the auditory stimulus, (2) only a few of the subjects who did not initially orient could be taught to respond, (3) of the children who initially oriented or were taught to respond, thresholds were obtained on a large number (81%) in one visit, and (4) a systematic relationship was demonstrated between consistency of subject response using the VRA technique and BSID Mental Age Equivalent with 10 months being the critical age for determining the potential success of the procedure. In addition, the results implied a higher incidence of hearing loss in the Down's syndrome subjects than found in normal pediatric population."} {"id": "PMID:153436", "title": "Purification and characteristics of hydrophobic membrane protein(s) required for DCCD sensitivity of ATPase in Mycobacterium phlei.", "content": "The energy-transducing N,N'-dicyclohexylcarbodiimide-sensitive (DCCD-sensitive) ATPase complex consists of two parts, a soluble catalytic protein (F1), and an intrinsic membrane protein (F0). The bacterial coupling factor complex, BCF0-BCF1, has recently been purified from Mycobacterium phlei, and used to reconstitute oxidative phosphorylation in detergent-extracted membranes. The BCF0 moiety has been purified by being recovered from the purified BCF0-BCF1 complex by affinity chromatography. BCF0 is a lipoprotein or lipoprotein complex with an approximate molecular weight of 60,000. The preparation contained 0.15 mg of phospholipid per milligram protein. There appear to be three polypeptides, with approximate molecular weights of 24,000, 18,000, and 8,000 as determined by sodium dodecylsulfate acrylamide gel electrophoresis. Purified BCF0 conferred DCCD sensitivity on a purified BCF1 preparation. Reconstitution of oxidative phosphorylation was achieved after incubation of detergent-extracted membranes with purified BCF0 and purified BCF1.", "contents": "Purification and characteristics of hydrophobic membrane protein(s) required for DCCD sensitivity of ATPase in Mycobacterium phlei. The energy-transducing N,N'-dicyclohexylcarbodiimide-sensitive (DCCD-sensitive) ATPase complex consists of two parts, a soluble catalytic protein (F1), and an intrinsic membrane protein (F0). The bacterial coupling factor complex, BCF0-BCF1, has recently been purified from Mycobacterium phlei, and used to reconstitute oxidative phosphorylation in detergent-extracted membranes. The BCF0 moiety has been purified by being recovered from the purified BCF0-BCF1 complex by affinity chromatography. BCF0 is a lipoprotein or lipoprotein complex with an approximate molecular weight of 60,000. The preparation contained 0.15 mg of phospholipid per milligram protein. There appear to be three polypeptides, with approximate molecular weights of 24,000, 18,000, and 8,000 as determined by sodium dodecylsulfate acrylamide gel electrophoresis. Purified BCF0 conferred DCCD sensitivity on a purified BCF1 preparation. Reconstitution of oxidative phosphorylation was achieved after incubation of detergent-extracted membranes with purified BCF0 and purified BCF1."} {"id": "PMID:153437", "title": "Erythrocyte troponin inhibitor-like protein: isolation and characterization.", "content": "A protein was isolated from a human erythrocyte lysate with an apparent molecular weight of 23,000--24,000 daltons. This protein was purified by batch DEAE cellulose followed by column DEAE cellulose chromatography and a gradient of NaCl. On sodium dodecyl sulfate acrylamide electrophoresis, the erythrocyte protein comigrated with muscle troponin inhibitor. An isoelectric precipitation (pH 9.25) was used for the separation of muscle troponin inhibitor from a complex with another troponin component. Both the erythrocyte protein and the muscle troponin inhibitor partially inhibited muscle myosin Ca2+ and K+-EDTA ATPase activity. Furthermore, they inhibited actin-activated Mg2+-ATPase of muscle myosin. The inhibitory effects were absent in the presence of muscle troponin calcium-binding component. Muscle troponin inhibitor and the erythrocyte troponin inhibitor-like protein bound to muscle myosin when myosin was precipitated twice at low ionic strength. The presence of a troponin inhibitor-like protein in erythrocytes suggests that it may be a component in the regulation of contractile activity.", "contents": "Erythrocyte troponin inhibitor-like protein: isolation and characterization. A protein was isolated from a human erythrocyte lysate with an apparent molecular weight of 23,000--24,000 daltons. This protein was purified by batch DEAE cellulose followed by column DEAE cellulose chromatography and a gradient of NaCl. On sodium dodecyl sulfate acrylamide electrophoresis, the erythrocyte protein comigrated with muscle troponin inhibitor. An isoelectric precipitation (pH 9.25) was used for the separation of muscle troponin inhibitor from a complex with another troponin component. Both the erythrocyte protein and the muscle troponin inhibitor partially inhibited muscle myosin Ca2+ and K+-EDTA ATPase activity. Furthermore, they inhibited actin-activated Mg2+-ATPase of muscle myosin. The inhibitory effects were absent in the presence of muscle troponin calcium-binding component. Muscle troponin inhibitor and the erythrocyte troponin inhibitor-like protein bound to muscle myosin when myosin was precipitated twice at low ionic strength. The presence of a troponin inhibitor-like protein in erythrocytes suggests that it may be a component in the regulation of contractile activity."} {"id": "PMID:153438", "title": "An unusual mediastinal lipoma simulating cardiomegaly.", "content": "A patient with vague, nonspecific symptoms was initially thought to have an enlarged cardiac silhouette on chest roentgenogram, and a primary intracardiac disorder was suspected. At surgery, a mediastinal lipoma was diagnosed and excised. The roentgenographic appearance represents an unusual presentation of a mediastinal tumor.", "contents": "An unusual mediastinal lipoma simulating cardiomegaly. A patient with vague, nonspecific symptoms was initially thought to have an enlarged cardiac silhouette on chest roentgenogram, and a primary intracardiac disorder was suspected. At surgery, a mediastinal lipoma was diagnosed and excised. The roentgenographic appearance represents an unusual presentation of a mediastinal tumor."} {"id": "PMID:153442", "title": "Coenzyme dependent suppression of 2,2-PDS induced contractures in Spirostomum.", "content": "Spirostomum ambiguum was stimulated to contract by addition of the thiol inhibitor, 2,2-dithiobispyridine (PDS), which depletes intracellular reducing equivalents which are generated by coenzyme dependents reactions. PDS induced contractures were not suppressed after 2--4 h of pre-incubation in a medium enriched with ascorbic acid, thiamine, or riboflavin, singly. Two h of incubation with nicotinamide did not suppress contractures; however, 50% suppression occurred after 3 h incubation. Incubation of the cells in a medium enriched with all four coenzymes for up to 4 h, resulted in the suppression of PDS induced contractures to a level as low as 30% of control values. Suppression of contractures by the mixed coenzymes was concentration dependent. Cells that were stimulated with PDS and contracting, exhibited a 50% suppression of contractures within 3 min after transfer to a complementary medium enriched with mixed coenzymes. These results suggest that coenzymes interact synergistically with cellular metabolic processes to inhibit pharmacodynamic responses to PDS.", "contents": "Coenzyme dependent suppression of 2,2-PDS induced contractures in Spirostomum. Spirostomum ambiguum was stimulated to contract by addition of the thiol inhibitor, 2,2-dithiobispyridine (PDS), which depletes intracellular reducing equivalents which are generated by coenzyme dependents reactions. PDS induced contractures were not suppressed after 2--4 h of pre-incubation in a medium enriched with ascorbic acid, thiamine, or riboflavin, singly. Two h of incubation with nicotinamide did not suppress contractures; however, 50% suppression occurred after 3 h incubation. Incubation of the cells in a medium enriched with all four coenzymes for up to 4 h, resulted in the suppression of PDS induced contractures to a level as low as 30% of control values. Suppression of contractures by the mixed coenzymes was concentration dependent. Cells that were stimulated with PDS and contracting, exhibited a 50% suppression of contractures within 3 min after transfer to a complementary medium enriched with mixed coenzymes. These results suggest that coenzymes interact synergistically with cellular metabolic processes to inhibit pharmacodynamic responses to PDS."} {"id": "PMID:153444", "title": "Prenatal diagnosis in New South Wales: comparative view of the first 1000 cases of chromosomal, sex-linked, and metabolic referrals.", "content": "In 1000 cases referred for prenatal diagnosis, 28 affected fetuses were detected, and 24 therapeutic terminations of pregnancy were performed. There were five main reasons for referral. Among the 293 women referred because of advanced maternal age (40 years and above), there were 11 (3.8%) who had affected fetuses, while among the 439 aged 35 to 39 years there were 6 such women (1.4%). In the 112 mothers referred because of a history of a previous child with Down's syndrome, one fetus (0.9%) with trisomy 21 was detected. Of 27 cases in which one parent was a carrier of a balanced chromosomal rearrangement, two chromosomally abnormal fetuses (7.4%) were detected (the offspring of maternal carriers), and a further two spontaneous abortions occurred before the scheduled amniocentesis. In the 22 cases with a history of sex-linked disorder, there were 8 males. Nine women were referred with a possible inherited metabolic defect: one fetus affected with congenital adrenal hyperplasia was detected. The number of metabolic referrals was markedly less than in overseas studies. The finding of XXY, XXX and trisomies of chromosomes 13, 18, and 21 in fetuses of older mothers confirms the increased risk in such mothers for chromosome abnormalities in addition to trisomy 21. Sixty-two of the 1000 women (6.2%) had to have a repeat amniocentesis because of failure of culture. Of 900 births: one case of maternal cell contamination and one case of unconfirmed mosaicism were the only disparities between prenatal and postnatal karyotypes. The average time necessary to obtain the karyotypic result was 15 days after amniocentesis.", "contents": "Prenatal diagnosis in New South Wales: comparative view of the first 1000 cases of chromosomal, sex-linked, and metabolic referrals. In 1000 cases referred for prenatal diagnosis, 28 affected fetuses were detected, and 24 therapeutic terminations of pregnancy were performed. There were five main reasons for referral. Among the 293 women referred because of advanced maternal age (40 years and above), there were 11 (3.8%) who had affected fetuses, while among the 439 aged 35 to 39 years there were 6 such women (1.4%). In the 112 mothers referred because of a history of a previous child with Down's syndrome, one fetus (0.9%) with trisomy 21 was detected. Of 27 cases in which one parent was a carrier of a balanced chromosomal rearrangement, two chromosomally abnormal fetuses (7.4%) were detected (the offspring of maternal carriers), and a further two spontaneous abortions occurred before the scheduled amniocentesis. In the 22 cases with a history of sex-linked disorder, there were 8 males. Nine women were referred with a possible inherited metabolic defect: one fetus affected with congenital adrenal hyperplasia was detected. The number of metabolic referrals was markedly less than in overseas studies. The finding of XXY, XXX and trisomies of chromosomes 13, 18, and 21 in fetuses of older mothers confirms the increased risk in such mothers for chromosome abnormalities in addition to trisomy 21. Sixty-two of the 1000 women (6.2%) had to have a repeat amniocentesis because of failure of culture. Of 900 births: one case of maternal cell contamination and one case of unconfirmed mosaicism were the only disparities between prenatal and postnatal karyotypes. The average time necessary to obtain the karyotypic result was 15 days after amniocentesis."} {"id": "PMID:153445", "title": "Huntington's disease: the establishment of a national register.", "content": "The historical background of Huntington's disease in Australia is briefly described, together with the development of professional and self-help groups. An existing Huntington's disease register in Victoria is described in detail. A case is made for the need for the establishment of an Australia-wide register of Huntington's disease. Certain ethical issues and safeguards necessary to such a register are discussed.", "contents": "Huntington's disease: the establishment of a national register. The historical background of Huntington's disease in Australia is briefly described, together with the development of professional and self-help groups. An existing Huntington's disease register in Victoria is described in detail. A case is made for the need for the establishment of an Australia-wide register of Huntington's disease. Certain ethical issues and safeguards necessary to such a register are discussed."} {"id": "PMID:153470", "title": "[Advances in topical therapy of skin diseases (author's transl)].", "content": "The anti-inflammatory effect of the new topical corticosteroid fluocortin butyl ester is approximately equal to that of hydrocortisone acetate but it has the advantage that systemic side-effects are lacking. Vitamin A acid and benzoyl peroxide have brought significant advances in the topical treatment of acne. For the treatment of chloasma and other hyperpigmentations the combination of vitamin A acid and hydroquinone with a corticoid is considerably more effective than any of the single components alone. Povidone-iodine with its extraordinarily low sensitization rate has proved useful for external antimicrobial treatment. Extensive or multiple precancerous lesions are effectively treated with 5-fluorouracil. New hair growth can be induced in alopecia areata by the local application of DNCB.", "contents": "[Advances in topical therapy of skin diseases (author's transl)]. The anti-inflammatory effect of the new topical corticosteroid fluocortin butyl ester is approximately equal to that of hydrocortisone acetate but it has the advantage that systemic side-effects are lacking. Vitamin A acid and benzoyl peroxide have brought significant advances in the topical treatment of acne. For the treatment of chloasma and other hyperpigmentations the combination of vitamin A acid and hydroquinone with a corticoid is considerably more effective than any of the single components alone. Povidone-iodine with its extraordinarily low sensitization rate has proved useful for external antimicrobial treatment. Extensive or multiple precancerous lesions are effectively treated with 5-fluorouracil. New hair growth can be induced in alopecia areata by the local application of DNCB."} {"id": "PMID:153471", "title": "Prenatal genetic diagnosis in 3000 amniocenteses.", "content": "We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (greater than or equal to 35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate.", "contents": "Prenatal genetic diagnosis in 3000 amniocenteses. We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (greater than or equal to 35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate."} {"id": "PMID:153472", "title": "Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid.", "content": "Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland.", "contents": "Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland."} {"id": "PMID:153476", "title": "Effects of 6-aminonicotinamide on growth and acetylcholinesterase activity during differentiation of neuroblastoma cells in vitro.", "content": "Addition of 6-AN (0.01 mg/ml) to growing cultures of C-1300 neuroblastoma cells strongly reduced cell division. This growth inhibition was accompanied by a higher cell volume and a lower protein content per cell as compared to controls. Concurrently the specific activity of AChE increased markedly incontrols and 6-AN-treated cultures. During the experimental periods the specific activity of AChE was significantly higher after 6-AN. Morphologically, 6-AN-treated cultures showed characteristic signs of differentiation, i.e. enlarged, flattened cells with long branched processes. The described effect of 6-AN on growth and differentiation of neuroblastoma cells was less pronounced if cells received the antimetabolite after a subcultivation period of 5 days.", "contents": "Effects of 6-aminonicotinamide on growth and acetylcholinesterase activity during differentiation of neuroblastoma cells in vitro. Addition of 6-AN (0.01 mg/ml) to growing cultures of C-1300 neuroblastoma cells strongly reduced cell division. This growth inhibition was accompanied by a higher cell volume and a lower protein content per cell as compared to controls. Concurrently the specific activity of AChE increased markedly incontrols and 6-AN-treated cultures. During the experimental periods the specific activity of AChE was significantly higher after 6-AN. Morphologically, 6-AN-treated cultures showed characteristic signs of differentiation, i.e. enlarged, flattened cells with long branched processes. The described effect of 6-AN on growth and differentiation of neuroblastoma cells was less pronounced if cells received the antimetabolite after a subcultivation period of 5 days."} {"id": "PMID:153477", "title": "Chronic hypertension induced by streptozotocin in rats.", "content": "An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progessively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic beta-cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin.", "contents": "Chronic hypertension induced by streptozotocin in rats. An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progessively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic beta-cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin."} {"id": "PMID:153478", "title": "Effect of p-chlorophenylalanine on cerebral serotonin binding, serotonin concentration and motor activity in the rat.", "content": "The effect of p-chlorophenylalanine (PCPA) on the specific binding of 3H-serotonin (5-HT) was investigated in crude membrane preparations of the rat forebrain. The level of cerebral 5-HT and 5-hydroxyindoleacetic acid were concomitantly determined. A single dose of PCPA (300 mg/kg i.p.) increased specific binding at a low concentration of 3H-5-HT within 24 h by more than 100%. The time course of the elevation of specific binding was mirrored by the reduction in the 5-HT level. However, 8--10 days after drug administration, specific binding was close to the control level, while 5-HT was still significantly reduced. A Scatchard analysis revealed that the apparent affinity was significantly increased (KD reduced) during the initial period after PCPA administration, whereas the number of binding sites (BMax) was little changed. In contrast, after reported injections of PCPA (3 injections of 300 mg/kg at 6--8 day intervals, or 100 mg/kg/day for up to 12 days) leading to a prolonged 5-HT depletion, BMax was significantly increased, while KD tended to be restored towards the baseline level. Daily injections of PCPA (100 mg/kg) for 12 days resulted in a transitory increase in day-time motor activity with a maximum on drug day 3, and in a persistent reduction of night-time activity. It is concluded that the initial PCPA-induced decrease in KD was due to a reduced competition for binding sites by the endogenous 5-HT, whereas the increase of BMax after a prolonged 5-HT depletion may reflect a 5-HT receptor supersensitivity.", "contents": "Effect of p-chlorophenylalanine on cerebral serotonin binding, serotonin concentration and motor activity in the rat. The effect of p-chlorophenylalanine (PCPA) on the specific binding of 3H-serotonin (5-HT) was investigated in crude membrane preparations of the rat forebrain. The level of cerebral 5-HT and 5-hydroxyindoleacetic acid were concomitantly determined. A single dose of PCPA (300 mg/kg i.p.) increased specific binding at a low concentration of 3H-5-HT within 24 h by more than 100%. The time course of the elevation of specific binding was mirrored by the reduction in the 5-HT level. However, 8--10 days after drug administration, specific binding was close to the control level, while 5-HT was still significantly reduced. A Scatchard analysis revealed that the apparent affinity was significantly increased (KD reduced) during the initial period after PCPA administration, whereas the number of binding sites (BMax) was little changed. In contrast, after reported injections of PCPA (3 injections of 300 mg/kg at 6--8 day intervals, or 100 mg/kg/day for up to 12 days) leading to a prolonged 5-HT depletion, BMax was significantly increased, while KD tended to be restored towards the baseline level. Daily injections of PCPA (100 mg/kg) for 12 days resulted in a transitory increase in day-time motor activity with a maximum on drug day 3, and in a persistent reduction of night-time activity. It is concluded that the initial PCPA-induced decrease in KD was due to a reduced competition for binding sites by the endogenous 5-HT, whereas the increase of BMax after a prolonged 5-HT depletion may reflect a 5-HT receptor supersensitivity."} {"id": "PMID:153480", "title": "[Enlarged operations for atypical lombo-sciatic pain from disk origin (author's transl)].", "content": "In certain forms of atypical sciatic pain the surgical treatment of the affection cannot be accomplished exclusively upon the disk. This study was done on 120 patients operated upon during a two year period. The major technics used had an action upon the articular processes and facets with or without removal of the disk. In 60 cases a desensibilisation of the region was equally done. The principal reason of the surgical treatment remains still to permit the decompression of the sick root. In certain circumstances a more important surgical treatment is required: laminectomy is performed in cases of stenosis or in other cases an inter body fusion by posterior approach (60 patients). The term atypical lombo-sciatic pain is applied essentially when there exists discordancy in the clinical and neuroradiological examination. Surgical cure is applied when the medical treatment has failed. The best results have been obtained in atypical sciatic pain when facet rhizolysis has been associated with root decompression. However great care was taken to prevent the act from being destructive.", "contents": "[Enlarged operations for atypical lombo-sciatic pain from disk origin (author's transl)]. In certain forms of atypical sciatic pain the surgical treatment of the affection cannot be accomplished exclusively upon the disk. This study was done on 120 patients operated upon during a two year period. The major technics used had an action upon the articular processes and facets with or without removal of the disk. In 60 cases a desensibilisation of the region was equally done. The principal reason of the surgical treatment remains still to permit the decompression of the sick root. In certain circumstances a more important surgical treatment is required: laminectomy is performed in cases of stenosis or in other cases an inter body fusion by posterior approach (60 patients). The term atypical lombo-sciatic pain is applied essentially when there exists discordancy in the clinical and neuroradiological examination. Surgical cure is applied when the medical treatment has failed. The best results have been obtained in atypical sciatic pain when facet rhizolysis has been associated with root decompression. However great care was taken to prevent the act from being destructive."} {"id": "PMID:153481", "title": "The influence of the nervous system upon adrenal gland weight and assayable pituitary MSH.", "content": "A series of experiments were designed to test the assumption that neuroregulatory mechanisms associated with pituitary ACTH and melanotropin (MSH) secretions are interdependent. Stress elevates both ACTH and MSH activity in mouse pituitaries. There are nervous influences on the secretion of both of these hormones. We have undertaken to stimulate or block various components of the nervous control of these 2 hormones in order to determine whether the 2 are controlled by the same mechanisms or separate ones. We have exposed mice to neurotransmitter blocking agents against serotonin, norepinephrine and epinephrin--parachlorophenylalanine (PCPA), alpha-methyltyrosine (MT), propranolol--both with and without stress. Unilateral adrenalectomy with and without hydrocortisone replacement therapy were investigated. We found that none of the neuro-active substances altered stress elevation of ACTH and MSH. Unilaterally adrenalectomized stressed animals treated with hydrocortisone showed elevated pituitary MSH levels but non increased ACTH release, as measured by size of the remaining adrenal. Adrenalectomy of animals without replacement therapy showed both elevated pituitary MSH and increased ACTH activity. Since the ACTH and MSH activity behave independently in the last described experiments, we conclude that ACTH and MSH are independently controlled.", "contents": "The influence of the nervous system upon adrenal gland weight and assayable pituitary MSH. A series of experiments were designed to test the assumption that neuroregulatory mechanisms associated with pituitary ACTH and melanotropin (MSH) secretions are interdependent. Stress elevates both ACTH and MSH activity in mouse pituitaries. There are nervous influences on the secretion of both of these hormones. We have undertaken to stimulate or block various components of the nervous control of these 2 hormones in order to determine whether the 2 are controlled by the same mechanisms or separate ones. We have exposed mice to neurotransmitter blocking agents against serotonin, norepinephrine and epinephrin--parachlorophenylalanine (PCPA), alpha-methyltyrosine (MT), propranolol--both with and without stress. Unilateral adrenalectomy with and without hydrocortisone replacement therapy were investigated. We found that none of the neuro-active substances altered stress elevation of ACTH and MSH. Unilaterally adrenalectomized stressed animals treated with hydrocortisone showed elevated pituitary MSH levels but non increased ACTH release, as measured by size of the remaining adrenal. Adrenalectomy of animals without replacement therapy showed both elevated pituitary MSH and increased ACTH activity. Since the ACTH and MSH activity behave independently in the last described experiments, we conclude that ACTH and MSH are independently controlled."} {"id": "PMID:153484", "title": "Long term treatment of Huntington disease with L-glutamate and pyridoxine.", "content": "Decreased levels of gamma aminobutyric acid (GABA) and its synthetic enzyme, glutamic acid decarboxylase, have been found in the brains of patients with Huntington disease. In an attempt to augment GABA-mediated neurotransmission, daily doses of 25 gm of L-glutamate (the substrate for glutamic acid decarboxylase) and 500 mg of pyridoxine, its cofactor, were given to five patients with Huntington disease. This regimen was continued for 2 years. Assessment of motor and behavioral function indicated no improvement on this regimen.", "contents": "Long term treatment of Huntington disease with L-glutamate and pyridoxine. Decreased levels of gamma aminobutyric acid (GABA) and its synthetic enzyme, glutamic acid decarboxylase, have been found in the brains of patients with Huntington disease. In an attempt to augment GABA-mediated neurotransmission, daily doses of 25 gm of L-glutamate (the substrate for glutamic acid decarboxylase) and 500 mg of pyridoxine, its cofactor, were given to five patients with Huntington disease. This regimen was continued for 2 years. Assessment of motor and behavioral function indicated no improvement on this regimen."} {"id": "PMID:153486", "title": "[Proposed model for evaluation of toxicity in antineoplastic chemo-hormonotherapy].", "content": "A detailed code for the evaluation of side-effects due to antiblastics in accordance with clinical, pharmacological and chronobiological parameters is described. Eight types of toxicity are recognised: systemic or local, cutaneous and adnexal, gastroenteric, haematochemical, cardiovascular, respiratory, genital and urinary, and nervous. Improvement of the objectivity and comparability of results in clinical oncology is proposed by means of a balanced points system for the expression of such effects, and methods for the summary expression of the toxicity of a single case or a uniform group of cases. The method of evaluation proposed also permits statistical comparison between different treatment protocols.", "contents": "[Proposed model for evaluation of toxicity in antineoplastic chemo-hormonotherapy]. A detailed code for the evaluation of side-effects due to antiblastics in accordance with clinical, pharmacological and chronobiological parameters is described. Eight types of toxicity are recognised: systemic or local, cutaneous and adnexal, gastroenteric, haematochemical, cardiovascular, respiratory, genital and urinary, and nervous. Improvement of the objectivity and comparability of results in clinical oncology is proposed by means of a balanced points system for the expression of such effects, and methods for the summary expression of the toxicity of a single case or a uniform group of cases. The method of evaluation proposed also permits statistical comparison between different treatment protocols."} {"id": "PMID:153487", "title": "[Current role of pancreatic scintiscanning in the study of pancreatic symptomatology].", "content": "A brief reference is made to the part once assigned to scintiscanning as a method of approach to diseases of the pancreas. It is felt that the lack of confidence now displayed in this technique is based preconceptions. A new diagnostic approach is therefore proposed and briefly described. The advantages and disadvantages of the diagnostic techniques included in the proposed scheme are examined. The view is expressed that a fresh assessment should be made of nuclear pancreatography, since it is still a fundamental diagnostic tool.", "contents": "[Current role of pancreatic scintiscanning in the study of pancreatic symptomatology]. A brief reference is made to the part once assigned to scintiscanning as a method of approach to diseases of the pancreas. It is felt that the lack of confidence now displayed in this technique is based preconceptions. A new diagnostic approach is therefore proposed and briefly described. The advantages and disadvantages of the diagnostic techniques included in the proposed scheme are examined. The view is expressed that a fresh assessment should be made of nuclear pancreatography, since it is still a fundamental diagnostic tool."} {"id": "PMID:153489", "title": "[Uses in vascular symptomatology of the ultrasonic flowmeter with Doppler effect in patients revascularized for peripheral obliterating arteritis].", "content": "The Authors present 38 cases of surgical revascularization for arteriosclerosis obliterans of the lower extremities, operated in Clinica Chirurgica of Ancona during the space of three Years, from 1974-1977. The morphological profile of the sphygmic wave and pressures of occlusion or Travis Winsor's index were studied pre and postoperatively with Doppler ultrasonic flowmeter. The patency of vascular grafts and after thromboendarterectomy was shown by T.W.'s index. With this method, besides establishing a program for postoperative arteriography, a lesser use of the latter was shown.", "contents": "[Uses in vascular symptomatology of the ultrasonic flowmeter with Doppler effect in patients revascularized for peripheral obliterating arteritis]. The Authors present 38 cases of surgical revascularization for arteriosclerosis obliterans of the lower extremities, operated in Clinica Chirurgica of Ancona during the space of three Years, from 1974-1977. The morphological profile of the sphygmic wave and pressures of occlusion or Travis Winsor's index were studied pre and postoperatively with Doppler ultrasonic flowmeter. The patency of vascular grafts and after thromboendarterectomy was shown by T.W.'s index. With this method, besides establishing a program for postoperative arteriography, a lesser use of the latter was shown."} {"id": "PMID:153492", "title": "Laparoscopy in the evaluation of gynecologic cancer.", "content": "Laparoscopy was used to evaluate 60 patients with a variety of known or suspected gynecologic neoplasms. Diagnostic laparoscopy was performed on 18 patients to confirm benign or malignant pelvic masses or to confirm peritoneal carcinomatosis. Ten of these 18 patients (56%) were found to have unresectable carcinomatosis or benign disease which did not require further surgery. Staging laparoscopy was performed on 13 patients of which 3 had clinically unsuspected intraperitoneal spread of their disease. Surveillance laparoscopy was performed on 29 patients to determine the remission, regression, or progression of their disease following treatment; 8 (27%) had progressive or unresectable persistent disease. Despite the fact that the study comprised a high-risk group of previously operated on or irradiated patients, there was only one major complication. There was, however, a 10% incidence of laparoscopic failure from inadequate visualization. Twenty-one of the study patients (35%) were spared a laparotomy by the use of laparoscopy. The findings of this investigation help to identify those gynecologic oncology patients who should benefit most from the use of laparoscopy as an adjunct to the diagnosis, staging, or surveillance of intraabdominal malignant tumors.", "contents": "Laparoscopy in the evaluation of gynecologic cancer. Laparoscopy was used to evaluate 60 patients with a variety of known or suspected gynecologic neoplasms. Diagnostic laparoscopy was performed on 18 patients to confirm benign or malignant pelvic masses or to confirm peritoneal carcinomatosis. Ten of these 18 patients (56%) were found to have unresectable carcinomatosis or benign disease which did not require further surgery. Staging laparoscopy was performed on 13 patients of which 3 had clinically unsuspected intraperitoneal spread of their disease. Surveillance laparoscopy was performed on 29 patients to determine the remission, regression, or progression of their disease following treatment; 8 (27%) had progressive or unresectable persistent disease. Despite the fact that the study comprised a high-risk group of previously operated on or irradiated patients, there was only one major complication. There was, however, a 10% incidence of laparoscopic failure from inadequate visualization. Twenty-one of the study patients (35%) were spared a laparotomy by the use of laparoscopy. The findings of this investigation help to identify those gynecologic oncology patients who should benefit most from the use of laparoscopy as an adjunct to the diagnosis, staging, or surveillance of intraabdominal malignant tumors."} {"id": "PMID:153507", "title": "[New methods in early diagnosis of a cardiomyopathy caused by adriamycin].", "content": "The cytostatic drug Adriamycin can, when given in overdose, cause a congestive (dilative) cardiomyopathy. In 120 patients, chest X-ray and ECG proved unsuitable for the early detection of this cardiomyopathy. However, a relatively early diagnosis of a cardiomyopathy can be made using echocardiography, radiocardiography, including determination of the minimal cardiac transit time, and through the determination of systolic time intervals. Especially the latter method represents a simple, economic, and yet exact means for the early recognition of Adriamycin-induced cardiomyopathy.", "contents": "[New methods in early diagnosis of a cardiomyopathy caused by adriamycin]. The cytostatic drug Adriamycin can, when given in overdose, cause a congestive (dilative) cardiomyopathy. In 120 patients, chest X-ray and ECG proved unsuitable for the early detection of this cardiomyopathy. However, a relatively early diagnosis of a cardiomyopathy can be made using echocardiography, radiocardiography, including determination of the minimal cardiac transit time, and through the determination of systolic time intervals. Especially the latter method represents a simple, economic, and yet exact means for the early recognition of Adriamycin-induced cardiomyopathy."} {"id": "PMID:153509", "title": "Spinal injuries in Rangoon, Burma.", "content": "Spinal injuries in Burma as a result of a fall from height, especially from trees, in young male adults in low socio-economic classes; road traffic accidents are the second commonest cause; deep vein thrombosis and pulmonary embolism is very rare during the period of immobilisation. There are still some social problems of getting back to work and living conditions. We are trying our best to help the patients with spinal injuries.", "contents": "Spinal injuries in Rangoon, Burma. Spinal injuries in Burma as a result of a fall from height, especially from trees, in young male adults in low socio-economic classes; road traffic accidents are the second commonest cause; deep vein thrombosis and pulmonary embolism is very rare during the period of immobilisation. There are still some social problems of getting back to work and living conditions. We are trying our best to help the patients with spinal injuries."} {"id": "PMID:153511", "title": "[Diplostomiasis in fishes in lake farms and the ways for its control].", "content": "Diplostomosis is the most common disease affecting Coregonidae in lakes of Karelia where intensive fish farming is conducted. The most acute form of diplostomosis, cercariosis, is especially dangerous for larvae introduced into small water bodies. Depending on a season or weather conditions a shift in the infection rate of fishes with metacercariae takes place. Some ways for diplostomatosis prophylaxis are being suggested. Relatively shallow lakes with low miniralisation of water of sulphate type have been found to be most suitable for Coregonidae nurseries. The very specificity of the intensive use of lakes for fish farming offers possibilities for diplostomosis development. In lakes-nurseries with a regulated water regime the abundance of Lymnaeidae can be reduced by winter draining off the water. The chemical control of mollusks, local use of copper sulphate, is also possible under lake conditions.", "contents": "[Diplostomiasis in fishes in lake farms and the ways for its control]. Diplostomosis is the most common disease affecting Coregonidae in lakes of Karelia where intensive fish farming is conducted. The most acute form of diplostomosis, cercariosis, is especially dangerous for larvae introduced into small water bodies. Depending on a season or weather conditions a shift in the infection rate of fishes with metacercariae takes place. Some ways for diplostomatosis prophylaxis are being suggested. Relatively shallow lakes with low miniralisation of water of sulphate type have been found to be most suitable for Coregonidae nurseries. The very specificity of the intensive use of lakes for fish farming offers possibilities for diplostomosis development. In lakes-nurseries with a regulated water regime the abundance of Lymnaeidae can be reduced by winter draining off the water. The chemical control of mollusks, local use of copper sulphate, is also possible under lake conditions."} {"id": "PMID:153512", "title": "[Biological characteristics of mosquitoes of the Culex pipiens complex (Culicidae) in Abkhazia].", "content": "A high abundance of C. p. pipiens and C. p. molestus in the town of Sukhumi and its vicinity was recorded from June to October. According to siphonal indexes the 4-th-stage larvae of these mosquitoes differ from each other rather insignificantly. The females of C. p. pipiens exhibit a high fecundity within a warm period of the year which sharply falls by the autumn. During a two-year experiment with a basement micropopulation of C. p. molestus from a non-autogenous form of C. pipiens there was established a gradual increase in the number of autogenous and stenogamic individuals. At the carbohydrate feeding the majority of the first autogenous females with ripe eggs are at the 3-rd -4-th stage of obesity.", "contents": "[Biological characteristics of mosquitoes of the Culex pipiens complex (Culicidae) in Abkhazia]. A high abundance of C. p. pipiens and C. p. molestus in the town of Sukhumi and its vicinity was recorded from June to October. According to siphonal indexes the 4-th-stage larvae of these mosquitoes differ from each other rather insignificantly. The females of C. p. pipiens exhibit a high fecundity within a warm period of the year which sharply falls by the autumn. During a two-year experiment with a basement micropopulation of C. p. molestus from a non-autogenous form of C. pipiens there was established a gradual increase in the number of autogenous and stenogamic individuals. At the carbohydrate feeding the majority of the first autogenous females with ripe eggs are at the 3-rd -4-th stage of obesity."} {"id": "PMID:153521", "title": "Visual calibration of posture in normal and motor retarded Down's syndrome infants.", "content": "Infants with Down's syndrome are delayed in achieving motor milestones. When they first sit unsupported a discrepancy between visual and mechanical-vestibular indices of postural stability is less disruptive of their balance than in normal infants. Yet when they first stand unsupported, the same discrepancy disrupts balance more in these infants than in the normal infants. The effect of discrepant visual feedback also differs systematically as a function of the infants' experience of the posture. Monitoring posture in relation to a stable visual surround appears to be fundamental to the normal development of motor control.", "contents": "Visual calibration of posture in normal and motor retarded Down's syndrome infants. Infants with Down's syndrome are delayed in achieving motor milestones. When they first sit unsupported a discrepancy between visual and mechanical-vestibular indices of postural stability is less disruptive of their balance than in normal infants. Yet when they first stand unsupported, the same discrepancy disrupts balance more in these infants than in the normal infants. The effect of discrepant visual feedback also differs systematically as a function of the infants' experience of the posture. Monitoring posture in relation to a stable visual surround appears to be fundamental to the normal development of motor control."} {"id": "PMID:153523", "title": "The relationship of mechanical Vmax to myosin ATPase activity in rabbit and marmot ventricular muscle.", "content": "Papillary muscle mechanics and ventricular myosin calcium-activated ATPase activity were measured in the same heart as a function of temperature (8--28 degrees) in rabbits and marmots, in order to examine further the hypothesis that the velocity of cardiac muscle shortening at zero load (Vmax) is correlated with myosin ATPase activity. There was a similar Q10 for Vmax in each muscle type, as measured with isotonic afterloaded quick-releases at 30--33% time-to-peak tension; the calcium activated ATPase of myosin in the two muscle types also was similar. The least squares linear regression of rabbit Vmax on calcium-activated myosin ATPase activity was the same as in the marmot, so all the data were pooled to yield a linear regression (Y = 0.47 +/- 3.82X) with a high correlation between the two variables [r = 0.95, P less than 0.01 (ANOV)]. Furthermore, the correlation proved to be predictive of cardiac Vmax and myosin ATPase activity levels in other experiments where these two measurements decreased below normal as a result of hypertrophic growth. Consequently, the quantitative relationship between Vmax and myosin ATPase defined here may prove to be predictive of the ability of cardiac muscle to release bond energy.", "contents": "The relationship of mechanical Vmax to myosin ATPase activity in rabbit and marmot ventricular muscle. Papillary muscle mechanics and ventricular myosin calcium-activated ATPase activity were measured in the same heart as a function of temperature (8--28 degrees) in rabbits and marmots, in order to examine further the hypothesis that the velocity of cardiac muscle shortening at zero load (Vmax) is correlated with myosin ATPase activity. There was a similar Q10 for Vmax in each muscle type, as measured with isotonic afterloaded quick-releases at 30--33% time-to-peak tension; the calcium activated ATPase of myosin in the two muscle types also was similar. The least squares linear regression of rabbit Vmax on calcium-activated myosin ATPase activity was the same as in the marmot, so all the data were pooled to yield a linear regression (Y = 0.47 +/- 3.82X) with a high correlation between the two variables [r = 0.95, P less than 0.01 (ANOV)]. Furthermore, the correlation proved to be predictive of cardiac Vmax and myosin ATPase activity levels in other experiments where these two measurements decreased below normal as a result of hypertrophic growth. Consequently, the quantitative relationship between Vmax and myosin ATPase defined here may prove to be predictive of the ability of cardiac muscle to release bond energy."} {"id": "PMID:153529", "title": "DNA gyrase: subunit structure and ATPase activity of the purified enzyme.", "content": "DNA gyrase has been purified to near homogeneity from Escherichia coli. The enzyme consists of two subunits of molecular weights 90,000 and 100,000 present in roughly equimolar amounts. The subunits can be identified as the products of two genes, determining resistance to coumermycin A1 and novobiocin (cou) and to nalidixic acid and oxolinic acid (nalA), respectively. These antibiotics were previously shown to be specific inhibitors of DNA gyrase. The ATPase activity of DNA gyrase is stimulated by double-stranded DNA and strongly inhibited by novobiocin but is relatively insensitive to oxolinic acid. Covalent attachment of an ATP derivative to the smaller (coumermycin-specific) subunit is also inhibited by novobiocin, suggesting that this drug interferes with the energy-coupling aspect of the DNA supercoiling reaction by blocking the access of ATP to the enzyme.", "contents": "DNA gyrase: subunit structure and ATPase activity of the purified enzyme. DNA gyrase has been purified to near homogeneity from Escherichia coli. The enzyme consists of two subunits of molecular weights 90,000 and 100,000 present in roughly equimolar amounts. The subunits can be identified as the products of two genes, determining resistance to coumermycin A1 and novobiocin (cou) and to nalidixic acid and oxolinic acid (nalA), respectively. These antibiotics were previously shown to be specific inhibitors of DNA gyrase. The ATPase activity of DNA gyrase is stimulated by double-stranded DNA and strongly inhibited by novobiocin but is relatively insensitive to oxolinic acid. Covalent attachment of an ATP derivative to the smaller (coumermycin-specific) subunit is also inhibited by novobiocin, suggesting that this drug interferes with the energy-coupling aspect of the DNA supercoiling reaction by blocking the access of ATP to the enzyme."} {"id": "PMID:153530", "title": "Systemic administration of beta-endorphin: potent hypotensive effect involving a serotonergic pathway.", "content": "In normal adult rats anesthetized with urethane, intravenous injections of beta-endorphin (30--150 micrograms kg-1) induced a transient fall of blood pressure followed by a small hypertension and a prolonged hypotension. Prior administration of naloxone completely blocked these effects, whereas naloxone, given 1 hr after beta-endorphin, did not reverse the prolonged depressor phase of the opioid peptide. The effects of beta-endorphin on the arterial blood pressure were greatly reduced in animals pretreated with p-chlorophenylalanine, a specific depletor of serotonin. Moreover, in rats pretreated with potent serotonin antagonists such as cyproheptadine, mianserin, and metergoline, beta-endorphin did not produce a significant hypotension. Furthermore, the depressor effect of beta-endorphin was potentiated by fluoxetine, a specific serotonin uptake inhibitor. These observations suggest the participation of a serotonergic pathway in the action of beta-endorphin on the arterial blood pressure.", "contents": "Systemic administration of beta-endorphin: potent hypotensive effect involving a serotonergic pathway. In normal adult rats anesthetized with urethane, intravenous injections of beta-endorphin (30--150 micrograms kg-1) induced a transient fall of blood pressure followed by a small hypertension and a prolonged hypotension. Prior administration of naloxone completely blocked these effects, whereas naloxone, given 1 hr after beta-endorphin, did not reverse the prolonged depressor phase of the opioid peptide. The effects of beta-endorphin on the arterial blood pressure were greatly reduced in animals pretreated with p-chlorophenylalanine, a specific depletor of serotonin. Moreover, in rats pretreated with potent serotonin antagonists such as cyproheptadine, mianserin, and metergoline, beta-endorphin did not produce a significant hypotension. Furthermore, the depressor effect of beta-endorphin was potentiated by fluoxetine, a specific serotonin uptake inhibitor. These observations suggest the participation of a serotonergic pathway in the action of beta-endorphin on the arterial blood pressure."} {"id": "PMID:153531", "title": "Biphasic effects of the antiserotonergic methysergide on lordosis in rats.", "content": "As also reported by other workers, the antiserotonergic drug methysergide was found to facilitate lordotic responding in estrogen primed, ovariectomized rats. A second dose of methysergide 24 hr after the first, however, failed to produce any increment in responding. Animals received daily estrogen injections in order to maintain a relatively constant level of priming. After several days of methysergide, a progesterone injection facilitated lordosis to the same degree as in controls receiving only saline and estrogen. When a second injection of progesterone was given 24 hr later, however, the animals failed to respond. In contrast, saline controls with this estrogen paradigm responded equally well to both progesterone injections. These results are discussed in terms of their bearing on possible serotonergic and non-serotonergic mechanisms by which progesterone may control lordosis.", "contents": "Biphasic effects of the antiserotonergic methysergide on lordosis in rats. As also reported by other workers, the antiserotonergic drug methysergide was found to facilitate lordotic responding in estrogen primed, ovariectomized rats. A second dose of methysergide 24 hr after the first, however, failed to produce any increment in responding. Animals received daily estrogen injections in order to maintain a relatively constant level of priming. After several days of methysergide, a progesterone injection facilitated lordosis to the same degree as in controls receiving only saline and estrogen. When a second injection of progesterone was given 24 hr later, however, the animals failed to respond. In contrast, saline controls with this estrogen paradigm responded equally well to both progesterone injections. These results are discussed in terms of their bearing on possible serotonergic and non-serotonergic mechanisms by which progesterone may control lordosis."} {"id": "PMID:153534", "title": "A review of muscle transplantation in mammals.", "content": "Recent research in the field of mammalian muscle transplantation is reviewed with respect to the typical postoperative course of a free muscle graft. Several questions of clinical relevance are discussed, such as 1) whether or not predenervation of a muscle graft is necessary, 2) the issue of survival vs. regeneration of muscle fibres within the graft, and 3) whether or not a muscle must be grafted as an intact anatomical unit. In addition problems of neuromuscular relations are discussed.", "contents": "A review of muscle transplantation in mammals. Recent research in the field of mammalian muscle transplantation is reviewed with respect to the typical postoperative course of a free muscle graft. Several questions of clinical relevance are discussed, such as 1) whether or not predenervation of a muscle graft is necessary, 2) the issue of survival vs. regeneration of muscle fibres within the graft, and 3) whether or not a muscle must be grafted as an intact anatomical unit. In addition problems of neuromuscular relations are discussed."} {"id": "PMID:153532", "title": "[The ultrasonic flowmeter : its use to measure peripheral venous circulation].", "content": "Using an ultrasonic flow-meter, the author measured, in the internal saphenous vein, the speed of the venous blood in various functional instances of tibiotarsal articulation. He was able to establish the essential role of this articulation in starting up the venous return flow, whence he infers a prophylactic approach to venous thrombosis.", "contents": "[The ultrasonic flowmeter : its use to measure peripheral venous circulation]. Using an ultrasonic flow-meter, the author measured, in the internal saphenous vein, the speed of the venous blood in various functional instances of tibiotarsal articulation. He was able to establish the essential role of this articulation in starting up the venous return flow, whence he infers a prophylactic approach to venous thrombosis."} {"id": "PMID:153538", "title": "Characterization of cardiac myosin from rabbit embryos and adult rabbits.", "content": "1. Ca2+-ATPase of myosin and electrophoretic pattern of light chains of myosin were investigated in cardiac muscles of 22-day-old rabbit embryos, new-born and adult rabbits. 2. Ca2+-ATPase activity was found to decrease during development and in contrast to that of adult rabbit, cardiac myosin prepared from 22-day-old embryos, is stable on exposure to pH 9.5. 3. Myosin from the cardiac muscle of rabbit embryos reveals light chains of both fast and slow types, that from adult animals, however, reveals light chains of the slow type only. 4. These studies suggest that unlike the cardiac muscle of adult rabbit, cardiac muscle of rabbit embryos contains both fast and slow types of myosin.", "contents": "Characterization of cardiac myosin from rabbit embryos and adult rabbits. 1. Ca2+-ATPase of myosin and electrophoretic pattern of light chains of myosin were investigated in cardiac muscles of 22-day-old rabbit embryos, new-born and adult rabbits. 2. Ca2+-ATPase activity was found to decrease during development and in contrast to that of adult rabbit, cardiac myosin prepared from 22-day-old embryos, is stable on exposure to pH 9.5. 3. Myosin from the cardiac muscle of rabbit embryos reveals light chains of both fast and slow types, that from adult animals, however, reveals light chains of the slow type only. 4. These studies suggest that unlike the cardiac muscle of adult rabbit, cardiac muscle of rabbit embryos contains both fast and slow types of myosin."} {"id": "PMID:153539", "title": "Membrane currents in a calcium type muscle membrane under voltage clamp.", "content": "Four ionic current components were identified in the total membrane current recorded under voltage clamp conditions from the muscle membrane of the crayfish (Astacus fluviatilis). The early inward current component is dependent on the presence of Ca2+ ions, disappears in Ca2+ free solutions and is insensitive to variaton of external Na+ ions and to tetrodotoxin. The outward current consists of at least three components, an early, a late and a slow outward current. The outward currents are sensitive to TEA and their reversal potentials differ. The early potassium current may be separated in a proportion of fibres by a hump from the later potassium current. An insufficient space clamp as a cause of the hump was excluded by comparing the size of the clamped membrane area with the distribution of large membrane clefts in the fibre. The early outward current is critically dependent on the presence of Ca2+ ions and is relatively more sensitive to TEA ions and to conditioning depolarisation than the late outward current.", "contents": "Membrane currents in a calcium type muscle membrane under voltage clamp. Four ionic current components were identified in the total membrane current recorded under voltage clamp conditions from the muscle membrane of the crayfish (Astacus fluviatilis). The early inward current component is dependent on the presence of Ca2+ ions, disappears in Ca2+ free solutions and is insensitive to variaton of external Na+ ions and to tetrodotoxin. The outward current consists of at least three components, an early, a late and a slow outward current. The outward currents are sensitive to TEA and their reversal potentials differ. The early potassium current may be separated in a proportion of fibres by a hump from the later potassium current. An insufficient space clamp as a cause of the hump was excluded by comparing the size of the clamped membrane area with the distribution of large membrane clefts in the fibre. The early outward current is critically dependent on the presence of Ca2+ ions and is relatively more sensitive to TEA ions and to conditioning depolarisation than the late outward current."} {"id": "PMID:153540", "title": "Changes in electrical properties of muscle membrane systems during decoupling and recoupling induced by glycerol.", "content": "In isolated muscle fibres of the frog and of the crayfish the following electrical parameters were determined during the glycerol procedure from the voltage transients at 20 degrees C: the sarcoplasmic resistivity, Ri; the membrane resistance, Rm; the series tubular resistance, Rs; the surface membrane capacity, Cm; the tubular membrane capacity CT. No significant changes were found in fibres equilibrated with glycerol (G) saline. During the washout of glycerol only Ri and Cm remained unchanged. In reversibly decoupled crayfish fibres (300 mM-G) CT decreased to 70%, Rs increased to 175% and Rm increased to 200% of the control values. The changed parameters returned to control values upon reapplication of glycerol. In irreversibly decoupled fibres (500 and 600 mM-G) the changes in CT and Rs were more pronounced; and Rm was decreased. The resting potential remained constant with few mV. In frog fibres the changes in electrical parameters were in the same direction except the decrease of Rm during reversible decoupling (150 mM-G). The corresponding changes in reversible and irreversibly (300 mM-G) detubulated fibres were as follows: CT--60 (80) %; Rs--10 (14) times; Rm--50 (35) %.", "contents": "Changes in electrical properties of muscle membrane systems during decoupling and recoupling induced by glycerol. In isolated muscle fibres of the frog and of the crayfish the following electrical parameters were determined during the glycerol procedure from the voltage transients at 20 degrees C: the sarcoplasmic resistivity, Ri; the membrane resistance, Rm; the series tubular resistance, Rs; the surface membrane capacity, Cm; the tubular membrane capacity CT. No significant changes were found in fibres equilibrated with glycerol (G) saline. During the washout of glycerol only Ri and Cm remained unchanged. In reversibly decoupled crayfish fibres (300 mM-G) CT decreased to 70%, Rs increased to 175% and Rm increased to 200% of the control values. The changed parameters returned to control values upon reapplication of glycerol. In irreversibly decoupled fibres (500 and 600 mM-G) the changes in CT and Rs were more pronounced; and Rm was decreased. The resting potential remained constant with few mV. In frog fibres the changes in electrical parameters were in the same direction except the decrease of Rm during reversible decoupling (150 mM-G). The corresponding changes in reversible and irreversibly (300 mM-G) detubulated fibres were as follows: CT--60 (80) %; Rs--10 (14) times; Rm--50 (35) %."} {"id": "PMID:153542", "title": "Chronic polyelectromyography in awake, unrestrained animals.", "content": "A procedure is described for making an implantable electrode array for recording EMG activity in muscles of awake, unrestrained animals (rats and cats) at rest, during rhythmic activity and in response to various reflexogenic stimuli. The electrode array consists of a percutaneous connector (covered with Dow-Corning Silastic Medical Adhesive), steel wire spiral leads contained in silicone tubing and silicone plate probes with platinum electrodes. These plate probes can be fixed either to the bone underneath the muscle, slipped under the fascia, or fixed between muscles. EMG records are presented of postural activity and ambulation in rats, mastication in cats and unilateral and bilateral spinal and supraspinal reflex responses in rat hind limb muscles up to 6 months after implantation. The advantages (and drawbacks) of this technique and its possible uses in neurophysiology are enumerated in the discussion.", "contents": "Chronic polyelectromyography in awake, unrestrained animals. A procedure is described for making an implantable electrode array for recording EMG activity in muscles of awake, unrestrained animals (rats and cats) at rest, during rhythmic activity and in response to various reflexogenic stimuli. The electrode array consists of a percutaneous connector (covered with Dow-Corning Silastic Medical Adhesive), steel wire spiral leads contained in silicone tubing and silicone plate probes with platinum electrodes. These plate probes can be fixed either to the bone underneath the muscle, slipped under the fascia, or fixed between muscles. EMG records are presented of postural activity and ambulation in rats, mastication in cats and unilateral and bilateral spinal and supraspinal reflex responses in rat hind limb muscles up to 6 months after implantation. The advantages (and drawbacks) of this technique and its possible uses in neurophysiology are enumerated in the discussion."} {"id": "PMID:153543", "title": "Evidence for the role of serotonin in the inhibition of specific motor responses.", "content": "Two behavioural paradigms were used to test the effects of serotonin depletion on a specific form of response inhibition. Treatment with both p-chlorophenylalanine (p-CPA) at 200 mg/kg and lesions of the medial raphe nucleus impaired the acquisition of a step-off passive-avoidance response. The experimental design allowed the elimination of alternative interpretations in terms of increased sensitivity to shock and increased responsiveness to stimuli. p-CPA also impaired response inhibition during an omission-training schedule. The results of the three studies support a general role of serotonin in withholding specific instrumental (reinforced) motor actions. The results contrast with those of studies supporting a role of noradrenaline in response inhibition. A tentative conclusion supports Konorski's (1967) suggestion for differentiation of various types of response inhibition that are mediated by different neurochemical systems.", "contents": "Evidence for the role of serotonin in the inhibition of specific motor responses. Two behavioural paradigms were used to test the effects of serotonin depletion on a specific form of response inhibition. Treatment with both p-chlorophenylalanine (p-CPA) at 200 mg/kg and lesions of the medial raphe nucleus impaired the acquisition of a step-off passive-avoidance response. The experimental design allowed the elimination of alternative interpretations in terms of increased sensitivity to shock and increased responsiveness to stimuli. p-CPA also impaired response inhibition during an omission-training schedule. The results of the three studies support a general role of serotonin in withholding specific instrumental (reinforced) motor actions. The results contrast with those of studies supporting a role of noradrenaline in response inhibition. A tentative conclusion supports Konorski's (1967) suggestion for differentiation of various types of response inhibition that are mediated by different neurochemical systems."} {"id": "PMID:153568", "title": "[Reformatory educational approaches in early special education of the physically handicapped - a survey based on the \"Journal for the Care of Cripples\" 1909--1929 (author's transl)].", "content": "An historical survey of special education of the physically handicapped is necessary because the dialectic relationship between the educational attention for the physically handicapped on the one hand and the educational rejection of the most severely handicapped on the other hand, seems to be occurring today as in the first decades of this century. At first, the article reviews the social-biological approach of the orthopaedist K. Biesalski and the \"educational psychology of cripples\" of H. W\u00fcrtz, who worked together with Biesalski. The educational demands for cripples which result from their theories are briefly described. The influence of reformatory educational theory on both the pre-scientific educational theories concerning cripples before 1920 and the experimental-psychological and special educational concepts until 1929 are outlined. Finally the article analyses the resource material including articles of Agahd 1909; Delitsch 1909; Denzer 1910; Plass 1912; W\u00fcrtz 1912, 1913; Legel 1914; K\u00f6hler 1926; Herold 1929 und Winkler 1929.", "contents": "[Reformatory educational approaches in early special education of the physically handicapped - a survey based on the \"Journal for the Care of Cripples\" 1909--1929 (author's transl)]. An historical survey of special education of the physically handicapped is necessary because the dialectic relationship between the educational attention for the physically handicapped on the one hand and the educational rejection of the most severely handicapped on the other hand, seems to be occurring today as in the first decades of this century. At first, the article reviews the social-biological approach of the orthopaedist K. Biesalski and the \"educational psychology of cripples\" of H. W\u00fcrtz, who worked together with Biesalski. The educational demands for cripples which result from their theories are briefly described. The influence of reformatory educational theory on both the pre-scientific educational theories concerning cripples before 1920 and the experimental-psychological and special educational concepts until 1929 are outlined. Finally the article analyses the resource material including articles of Agahd 1909; Delitsch 1909; Denzer 1910; Plass 1912; W\u00fcrtz 1912, 1913; Legel 1914; K\u00f6hler 1926; Herold 1929 und Winkler 1929."} {"id": "PMID:153569", "title": "[Physically handicapped pupils at a regular school - experiences of the school experiment \"Lichtenau\" (author's transl)].", "content": "As an experiment in integration, the joint placement of physically handicapped and non-disabled pupils into the regular class settings of a school belonging to the Hessisch-Lichtenau experiment makes special social and educational measures necessary both at school and in the residential home. The main activities have to be directed towards scientific studies of existing problems and their practical solutions. The following article describes the problems arising from the integrational efforts and suggests possible solutions.", "contents": "[Physically handicapped pupils at a regular school - experiences of the school experiment \"Lichtenau\" (author's transl)]. As an experiment in integration, the joint placement of physically handicapped and non-disabled pupils into the regular class settings of a school belonging to the Hessisch-Lichtenau experiment makes special social and educational measures necessary both at school and in the residential home. The main activities have to be directed towards scientific studies of existing problems and their practical solutions. The following article describes the problems arising from the integrational efforts and suggests possible solutions."} {"id": "PMID:153566", "title": "[The results of valgus osteotomy in severe osteoarthritis of the hip (author's transl)].", "content": "The authors analysed 150 consecutive cases of valgus osteotomy (Pauwels II) performed in cases of very severe osteoarthritis, and followed up for 3 to 10 years (average 6 years). The quality and the permanency of the results depend mainly on the morphology of the osteoarthritic hip. A satisfactory clinical and radiologic result is attained when the stresses in the joint have been reduced by improving the congruity of the joint surfaces using the cephalic medial osteophyte as part of these, and thus increasing the weight bearing surfaces. In osteoarthritis secondary to dysplasia (single dysplasia, subluxation, or luxation with support: 49 cases) valgus osteotomy gave 77 p. 100 good results, with 83 p. 100 painfree hips. This result persists 10 years (or more) for women operated before 50 years of age. The results are good in primary osteoarthritis occuring in active age (83 cases). When the hip was extruded by acetabular and cephalic osteophytes, 60 p. 100 good results, with 81 p. 100 painfree hips, have been obtained. In protrusive osteoarthritis and coxa profunda (18 cases) the valgus osteotomy slightly improved the range of movement but the relief of pain was usual (88 p. 100) and durable. The causes of failure (lack of mechanical improvement, osteoarthritis resulting more from biological disturbance--primary osteoarthritis--rather than from mechanical causes, influence of the age) have been sought for.", "contents": "[The results of valgus osteotomy in severe osteoarthritis of the hip (author's transl)]. The authors analysed 150 consecutive cases of valgus osteotomy (Pauwels II) performed in cases of very severe osteoarthritis, and followed up for 3 to 10 years (average 6 years). The quality and the permanency of the results depend mainly on the morphology of the osteoarthritic hip. A satisfactory clinical and radiologic result is attained when the stresses in the joint have been reduced by improving the congruity of the joint surfaces using the cephalic medial osteophyte as part of these, and thus increasing the weight bearing surfaces. In osteoarthritis secondary to dysplasia (single dysplasia, subluxation, or luxation with support: 49 cases) valgus osteotomy gave 77 p. 100 good results, with 83 p. 100 painfree hips. This result persists 10 years (or more) for women operated before 50 years of age. The results are good in primary osteoarthritis occuring in active age (83 cases). When the hip was extruded by acetabular and cephalic osteophytes, 60 p. 100 good results, with 81 p. 100 painfree hips, have been obtained. In protrusive osteoarthritis and coxa profunda (18 cases) the valgus osteotomy slightly improved the range of movement but the relief of pain was usual (88 p. 100) and durable. The causes of failure (lack of mechanical improvement, osteoarthritis resulting more from biological disturbance--primary osteoarthritis--rather than from mechanical causes, influence of the age) have been sought for."} {"id": "PMID:153571", "title": "Weak A.C. magnetic field effects: changes in cell sodium pump activity following whole animal exposure.", "content": "A biological system consisting of a cell membrane enzyme (Na+-K+)-ATPase responded to exposure to a weak A.C. magnetic field. Analysis of Na+ pump activity in normal mouse (A/J) tissue--(a) Kidney cortex and diaphragm after 11 days of exposure to a magnetic field of 55-60 gauss, 60Hz showed a significant reduction as did (b) liver tissue but at day 17 the levels had returned to the control values. Neuroblastoma cells (C1300) transplanted to A/J mice also showed a reduction in the (Na+-K+)-ATPase activity but this persisted at day 17.", "contents": "Weak A.C. magnetic field effects: changes in cell sodium pump activity following whole animal exposure. A biological system consisting of a cell membrane enzyme (Na+-K+)-ATPase responded to exposure to a weak A.C. magnetic field. Analysis of Na+ pump activity in normal mouse (A/J) tissue--(a) Kidney cortex and diaphragm after 11 days of exposure to a magnetic field of 55-60 gauss, 60Hz showed a significant reduction as did (b) liver tissue but at day 17 the levels had returned to the control values. Neuroblastoma cells (C1300) transplanted to A/J mice also showed a reduction in the (Na+-K+)-ATPase activity but this persisted at day 17."} {"id": "PMID:153574", "title": "Lumbar spinal manipulation on trial. Part I--clinical assessment.", "content": "Thirty-two patients with chronic low back pain were treated three times at weekly intervals with rotational manipulation. Patients with femoral or sciatic root pain were included provided they did not exhibit root compression signs. Background therapy of codeine phosphate was administered throughout. There was a significant increase in spinal flexion measured clinically during the three-week period of manipulation followed by a significant decrease in the three-week period after manipulation. The first week of manipulative treatment was more painful than the corresponding week in the control group but in the second and third weeks there was less pain in the manipulated group. Pain scores were reduced to a significant degree within four weeks of starting treatment only in the group manipulated in the first treatment period. Patients benefitting subjectively from manipulation were more likely to be older and to have had symptoms for a shorter period than those not deriving benefit. The age of onset of symptoms was significantly later in the responders.", "contents": "Lumbar spinal manipulation on trial. Part I--clinical assessment. Thirty-two patients with chronic low back pain were treated three times at weekly intervals with rotational manipulation. Patients with femoral or sciatic root pain were included provided they did not exhibit root compression signs. Background therapy of codeine phosphate was administered throughout. There was a significant increase in spinal flexion measured clinically during the three-week period of manipulation followed by a significant decrease in the three-week period after manipulation. The first week of manipulative treatment was more painful than the corresponding week in the control group but in the second and third weeks there was less pain in the manipulated group. Pain scores were reduced to a significant degree within four weeks of starting treatment only in the group manipulated in the first treatment period. Patients benefitting subjectively from manipulation were more likely to be older and to have had symptoms for a shorter period than those not deriving benefit. The age of onset of symptoms was significantly later in the responders."} {"id": "PMID:153575", "title": "Lumbar spinal manipulation on trial. Part II--radiological assessment.", "content": "In a trial of manipulation for chronic low back pain, radiographs of the lumbar spine and radiographic assessment of spinal motion were of no value in predicting or assessing the response of the patients to manipulation. Although radiography of the lumbar spine is a commonly requested investigation, it contributes little to the management of such patients except to exclude serious spinal pathology before any form of physical treatment is commenced.", "contents": "Lumbar spinal manipulation on trial. Part II--radiological assessment. In a trial of manipulation for chronic low back pain, radiographs of the lumbar spine and radiographic assessment of spinal motion were of no value in predicting or assessing the response of the patients to manipulation. Although radiography of the lumbar spine is a commonly requested investigation, it contributes little to the management of such patients except to exclude serious spinal pathology before any form of physical treatment is commenced."} {"id": "PMID:153576", "title": "Metabolic abnormalities of tryptophan and nicotinic acid in patients with rheumatoid arthritis.", "content": "The mean plasma total tryptophan concentration of 13 long-standing rheumatoid arthritis patients was found to be lower than that of seven nonrheumatoid control subjects, but the plasma nicotinic acid concentration was unchanged. In the rheumatoid patients the urinary excretion of the tryptophan metabolites, kynurenine, xanthurenic acid and 3-hydroxyanthranilic acid, was increased several fold, but the excretion of N-methylnicotinamide was normal. These findings are discussed in relationship to the dietary intakes of tryptophan, nicotinic acid and pyridoxine, the effect of antirheumatoid drugs on plasma tryptophan and liver tryptophan pyrrolase, and requirement of rheumatoid patients for pyridoxine.", "contents": "Metabolic abnormalities of tryptophan and nicotinic acid in patients with rheumatoid arthritis. The mean plasma total tryptophan concentration of 13 long-standing rheumatoid arthritis patients was found to be lower than that of seven nonrheumatoid control subjects, but the plasma nicotinic acid concentration was unchanged. In the rheumatoid patients the urinary excretion of the tryptophan metabolites, kynurenine, xanthurenic acid and 3-hydroxyanthranilic acid, was increased several fold, but the excretion of N-methylnicotinamide was normal. These findings are discussed in relationship to the dietary intakes of tryptophan, nicotinic acid and pyridoxine, the effect of antirheumatoid drugs on plasma tryptophan and liver tryptophan pyrrolase, and requirement of rheumatoid patients for pyridoxine."} {"id": "PMID:153577", "title": "Mobile arm supports: an evaluation.", "content": "The results of a follow-up survey of 124 patients fitted with mobile arm supports at Mary Marlborough Lodge between 1970 and 1976 are presented. Of the patients fitted with mobile arm supports 33% are known to have used them for over one year, and 47% of those who were contacted were still using them. The reasons for non-use and the implications of the necessity for readjustments are discussed.", "contents": "Mobile arm supports: an evaluation. The results of a follow-up survey of 124 patients fitted with mobile arm supports at Mary Marlborough Lodge between 1970 and 1976 are presented. Of the patients fitted with mobile arm supports 33% are known to have used them for over one year, and 47% of those who were contacted were still using them. The reasons for non-use and the implications of the necessity for readjustments are discussed."} {"id": "PMID:153580", "title": "[A family with progressive myoclonus epilepsy (author's transl)].", "content": "To begin, a survey of the literature concerning the group of progressive myoclonic epilepsies is presented, from the initial descriptions of Unverricht (1891) and Lundborg (1903) to the present. Recently several subforms of this nosologic entity have been delineated according to the mode of inheritance, time of manifestation, severity of course, and biochemical characteristics (i.e, eventual demonstration of mucopolysaccharide storage in Lafora bodies or diffuse in the central nervous system and other organs). The most useful classification stems from Diebold (1972): early (I) and late (II) forms of the Lafora type having autosomal recessive inheritance; an autosomal recessive early form (III) and an autosomal dominant late form (IV) with degenerative changes in the central nervous system without biochemical disturbances. The authors describe 3 young siblings from Southern Tyrol, who clinically manifested the cardinal symptoms of the disease in addition to extrapyramidal cerebellar disturbances. In spite of extensive bioptic and biochemical examinations, neither Lafora bodies nor diffuse deposits or excretion of mucopolysaccharides could be demonstrated. The distant blood relationship between the parents of these patients supports the assumption of an autosomal recessive mode of transmission. The relatively early manifestation of the disease and the demonstration of degenerative changes within the central nervous system suggest assignment of these patients to Diebold's subgroup III of the progressive myoclonic epilepsy.", "contents": "[A family with progressive myoclonus epilepsy (author's transl)]. To begin, a survey of the literature concerning the group of progressive myoclonic epilepsies is presented, from the initial descriptions of Unverricht (1891) and Lundborg (1903) to the present. Recently several subforms of this nosologic entity have been delineated according to the mode of inheritance, time of manifestation, severity of course, and biochemical characteristics (i.e, eventual demonstration of mucopolysaccharide storage in Lafora bodies or diffuse in the central nervous system and other organs). The most useful classification stems from Diebold (1972): early (I) and late (II) forms of the Lafora type having autosomal recessive inheritance; an autosomal recessive early form (III) and an autosomal dominant late form (IV) with degenerative changes in the central nervous system without biochemical disturbances. The authors describe 3 young siblings from Southern Tyrol, who clinically manifested the cardinal symptoms of the disease in addition to extrapyramidal cerebellar disturbances. In spite of extensive bioptic and biochemical examinations, neither Lafora bodies nor diffuse deposits or excretion of mucopolysaccharides could be demonstrated. The distant blood relationship between the parents of these patients supports the assumption of an autosomal recessive mode of transmission. The relatively early manifestation of the disease and the demonstration of degenerative changes within the central nervous system suggest assignment of these patients to Diebold's subgroup III of the progressive myoclonic epilepsy."} {"id": "PMID:153581", "title": "[Choreic dyskinesia and GABA - pharmaco-clinical approach. Preliminary note].", "content": "The effects of Baclofen, a gabamimetic drug, have been studied in 4 patients affected by Huntington's Chorea. The biochemical bases of Chorea are discussed in relation to the HVA modifications in the cerebrospinal fluid induced by the drug. Some interesting data on the extrapyramidal physiology may be achieved with further investigations in a greater group of patients.", "contents": "[Choreic dyskinesia and GABA - pharmaco-clinical approach. Preliminary note]. The effects of Baclofen, a gabamimetic drug, have been studied in 4 patients affected by Huntington's Chorea. The biochemical bases of Chorea are discussed in relation to the HVA modifications in the cerebrospinal fluid induced by the drug. Some interesting data on the extrapyramidal physiology may be achieved with further investigations in a greater group of patients."} {"id": "PMID:153582", "title": "Work conditions and health of locomotive engineers. II. Questionnaire study, mortality and disability.", "content": "A questionnaire study on work conditions, work organization, leisure time, social problems, and health was directed toward active and retired locomotive engineers. This article mainly presents responses of the active engineers. The active locomotive engineers quoted the irregular work hours as the worst occupational problem. They judged noise and vibration in the locomotive cabs as disturbing. The majority of the desired changes in the work and work conditions concerned work time. The most common complaints given on the questionnaire were back trouble, hypertension and dermatitis. Tiredness and exhaustion were the most prevalent neuropsychological symptoms. A retrospective follow-up survey on invalidity and mortality was made. Trainmen and railroad clerks were used as reference cohorts.The engineers had relatively high invalidity and mortality rates in comparison to the reference groups, especially with respect to cardiovascular diseases and malignant tumors. Higher rates for disease of the digestive system and hearing loss were also suggested by the results.", "contents": "Work conditions and health of locomotive engineers. II. Questionnaire study, mortality and disability. A questionnaire study on work conditions, work organization, leisure time, social problems, and health was directed toward active and retired locomotive engineers. This article mainly presents responses of the active engineers. The active locomotive engineers quoted the irregular work hours as the worst occupational problem. They judged noise and vibration in the locomotive cabs as disturbing. The majority of the desired changes in the work and work conditions concerned work time. The most common complaints given on the questionnaire were back trouble, hypertension and dermatitis. Tiredness and exhaustion were the most prevalent neuropsychological symptoms. A retrospective follow-up survey on invalidity and mortality was made. Trainmen and railroad clerks were used as reference cohorts.The engineers had relatively high invalidity and mortality rates in comparison to the reference groups, especially with respect to cardiovascular diseases and malignant tumors. Higher rates for disease of the digestive system and hearing loss were also suggested by the results."} {"id": "PMID:153583", "title": "Accumulation of a tetrahydroisoquinoline in phenylketonuria.", "content": "3',4'-Deoxynorlaudanosolinecarboxylic acid (DNLCA), a tetrahydroisoquinoline derived from dopamine and phenylpyruvic acid, has been detected by computerized mass fragmentography in urine of phenylketonuric children and in urine and brain of rats with experimentally induced hyperphenylalaninemia. Levels of DNLCA in brain of treated animals were more than tenfold higher than controls, and the excess tetrahydroisoquinoline appeared to accumulate in the cerebellum and cortex. DNLCA is a noncompetitive inhibitor of dopamine beta-hydroxylase (inhibition constant, Ki, = 0.42 mM) and is taken up by the brain.", "contents": "Accumulation of a tetrahydroisoquinoline in phenylketonuria. 3',4'-Deoxynorlaudanosolinecarboxylic acid (DNLCA), a tetrahydroisoquinoline derived from dopamine and phenylpyruvic acid, has been detected by computerized mass fragmentography in urine of phenylketonuric children and in urine and brain of rats with experimentally induced hyperphenylalaninemia. Levels of DNLCA in brain of treated animals were more than tenfold higher than controls, and the excess tetrahydroisoquinoline appeared to accumulate in the cerebellum and cortex. DNLCA is a noncompetitive inhibitor of dopamine beta-hydroxylase (inhibition constant, Ki, = 0.42 mM) and is taken up by the brain."} {"id": "PMID:153589", "title": "Peritoneoscopy in the management of breast cancer.", "content": "Peritoneoscopy has been recommended by the Combined Breast Clinic at the Provincial Hospital, Port Elizabeth, since 1975, mainly to confirm or exclude metastatic involvement of the liver. Experience with 27 procedures is reviewed. Peritoneoscopy is shown to be a useful aid in the staging and management of selected cases of breast cancer. Positive findings, confirmed by histological examination, were recorded for 5 patients. Negative findings in 22 patients were equally helpful, and were found to be reliable, in that none of these patients had evidence of liver involvement during the follow-up period, while in 5 patients there was evidence of metastases elsewhere.", "contents": "Peritoneoscopy in the management of breast cancer. Peritoneoscopy has been recommended by the Combined Breast Clinic at the Provincial Hospital, Port Elizabeth, since 1975, mainly to confirm or exclude metastatic involvement of the liver. Experience with 27 procedures is reviewed. Peritoneoscopy is shown to be a useful aid in the staging and management of selected cases of breast cancer. Positive findings, confirmed by histological examination, were recorded for 5 patients. Negative findings in 22 patients were equally helpful, and were found to be reliable, in that none of these patients had evidence of liver involvement during the follow-up period, while in 5 patients there was evidence of metastases elsewhere."} {"id": "PMID:153590", "title": "Acne, hypervitaminosis A and hypercalcaemia. A case report.", "content": "The ingestion of vitamin A, which is often prescribed for the treatment of acne, may lead to hypervitaminosis A. This syndrome has a wide spectrum of clinical features, hypercalcaemia being of special note since it has been reported in 4 previous cases only. Hypervitaminosis A has been described as resulting from excess ingestion of vitamin A for prevention of sunburn and treatment of minimal brain dysfunction. With the present glut of health foods, this condition should be borne in mind when patients present with symptoms of hypercalcaemia and liver dysfunction.", "contents": "Acne, hypervitaminosis A and hypercalcaemia. A case report. The ingestion of vitamin A, which is often prescribed for the treatment of acne, may lead to hypervitaminosis A. This syndrome has a wide spectrum of clinical features, hypercalcaemia being of special note since it has been reported in 4 previous cases only. Hypervitaminosis A has been described as resulting from excess ingestion of vitamin A for prevention of sunburn and treatment of minimal brain dysfunction. With the present glut of health foods, this condition should be borne in mind when patients present with symptoms of hypercalcaemia and liver dysfunction."} {"id": "PMID:153591", "title": "Attitudes toward the chronically ill and disabled: implications for the health care systems.", "content": "Health care services for the chronically ill are provided through a fragmented patchwork of activities by health care professionals. This article traces some of the origins of attitudes toward the chronically ill and identifies the problems created by disjointed patterns of care. A route for change that is humanistically based and uses a matrix model for care and management is suggested.", "contents": "Attitudes toward the chronically ill and disabled: implications for the health care systems. Health care services for the chronically ill are provided through a fragmented patchwork of activities by health care professionals. This article traces some of the origins of attitudes toward the chronically ill and identifies the problems created by disjointed patterns of care. A route for change that is humanistically based and uses a matrix model for care and management is suggested."} {"id": "PMID:153624", "title": "Steady-state gas exchange in normothermic, anesthetized, liquid-ventilated dogs.", "content": "Anesthetized, paralyzed, purebred beagle dogs were ventilated for 45 min (n = 5) and 60 min (n = 5) with oxygenated (PIO2 = 685 mmHg) FC-80 fluorocarbon liquid at 38 degrees C. The PaCO2 remained constant at approximately 43 mmHg during 60 min of liquid ventilation (mean tidal volume = 290 ml, mean respiratory frequency = 2.8 breaths/min). The end-tidal PCO2 was consistently higher than PaCO2 during liquid ventilation. Histological examination by light as well as scanning electron microscopy of the lungs of dogs killed 10, 30, or 180 days after liquid ventilation revealed no pathological changes except for a slight increase in the number of macrophages, especially around the alveolar ducts. It is concluded that a steady state of gas exchange at near normal arterial carbon dioxide partial pressures can be maintained in anesthetized, normothermic dogs ventilated with FC-80 at respiratory frequencies of approximately 3 breaths/min.", "contents": "Steady-state gas exchange in normothermic, anesthetized, liquid-ventilated dogs. Anesthetized, paralyzed, purebred beagle dogs were ventilated for 45 min (n = 5) and 60 min (n = 5) with oxygenated (PIO2 = 685 mmHg) FC-80 fluorocarbon liquid at 38 degrees C. The PaCO2 remained constant at approximately 43 mmHg during 60 min of liquid ventilation (mean tidal volume = 290 ml, mean respiratory frequency = 2.8 breaths/min). The end-tidal PCO2 was consistently higher than PaCO2 during liquid ventilation. Histological examination by light as well as scanning electron microscopy of the lungs of dogs killed 10, 30, or 180 days after liquid ventilation revealed no pathological changes except for a slight increase in the number of macrophages, especially around the alveolar ducts. It is concluded that a steady state of gas exchange at near normal arterial carbon dioxide partial pressures can be maintained in anesthetized, normothermic dogs ventilated with FC-80 at respiratory frequencies of approximately 3 breaths/min."} {"id": "PMID:153641", "title": "Cerebral neuroblastoma.", "content": "A cerebral neuroblastoma removed surgically from a female child is presented. Electron microscopy showed numerous neuronal processes with growth cones which are a feature of the developing neurone. In addition there were some rosettes with distinct lumina. The luminal surfaces were covered with a smooth plasma membrane lacking any surface differentiation and the lateral surface of these cells had many cell junctions (terminal bars), reminiscent of a primitive neural tube. These features in a nerve cell tumor help to substantiate it as a neuroblastoma arising from immature rather than differentiated cells. The nature of this rare tumor is discussed.", "contents": "Cerebral neuroblastoma. A cerebral neuroblastoma removed surgically from a female child is presented. Electron microscopy showed numerous neuronal processes with growth cones which are a feature of the developing neurone. In addition there were some rosettes with distinct lumina. The luminal surfaces were covered with a smooth plasma membrane lacking any surface differentiation and the lateral surface of these cells had many cell junctions (terminal bars), reminiscent of a primitive neural tube. These features in a nerve cell tumor help to substantiate it as a neuroblastoma arising from immature rather than differentiated cells. The nature of this rare tumor is discussed."} {"id": "PMID:153642", "title": "Granulomatous glomerulonephritis, without systemic disorder.", "content": "The case of a 12-year-old girl dying of renal insufficiency is described. At autopsy granulomatous glomerulonephritis was found without any systemic disease. The glomerular light-, immunofluorescent- and electron microscopic changes were studied. Four hundred glomeruli were analyzed by light microscopic investigation and graded (I-IV). By immunofluorescent investigation, intraglomerular and in the more severely affected glomeruli, periglomerular immunoglobulin deposition was detected. Electron microscopic investigation revealed mononuclear cells and fibroblasts in the glomerular and periglomerular cellular infiltrate, resulting in fragmentation and rupture of Bowman's capsule and loss of the glomerular structure.", "contents": "Granulomatous glomerulonephritis, without systemic disorder. The case of a 12-year-old girl dying of renal insufficiency is described. At autopsy granulomatous glomerulonephritis was found without any systemic disease. The glomerular light-, immunofluorescent- and electron microscopic changes were studied. Four hundred glomeruli were analyzed by light microscopic investigation and graded (I-IV). By immunofluorescent investigation, intraglomerular and in the more severely affected glomeruli, periglomerular immunoglobulin deposition was detected. Electron microscopic investigation revealed mononuclear cells and fibroblasts in the glomerular and periglomerular cellular infiltrate, resulting in fragmentation and rupture of Bowman's capsule and loss of the glomerular structure."} {"id": "PMID:153644", "title": "Lipofuscin and transsynaptic degeneration.", "content": "The periodic acid Schiff reaction was applied to neurones in the Lateral Geniculate Body (L.G.B.) of a series of normal and blind patients over a wide age range. The quantity of the reaction product was determined as a measure of lipofuscin which was found to increase linearly with age in the L.G.B. neurones. The amount in the neurones of the blind patients was found to be less than that in the controls, and a further group of four patients with apparently normal vision and central nervous system disease had an intermediate amount of lipofuscin. It is suggested that the component of lipofuscin measured by this technique represents an index of both metabolic activity and functional activity of the neurone. The reduced amounts in the patients with C.N.S. disease may reflect reduced visual function in association with non-visual pathway disease.", "contents": "Lipofuscin and transsynaptic degeneration. The periodic acid Schiff reaction was applied to neurones in the Lateral Geniculate Body (L.G.B.) of a series of normal and blind patients over a wide age range. The quantity of the reaction product was determined as a measure of lipofuscin which was found to increase linearly with age in the L.G.B. neurones. The amount in the neurones of the blind patients was found to be less than that in the controls, and a further group of four patients with apparently normal vision and central nervous system disease had an intermediate amount of lipofuscin. It is suggested that the component of lipofuscin measured by this technique represents an index of both metabolic activity and functional activity of the neurone. The reduced amounts in the patients with C.N.S. disease may reflect reduced visual function in association with non-visual pathway disease."} {"id": "PMID:153645", "title": "Capillarosclerosis of the lower urinary tract in analgesic (phenacetin) abuse. An electron-microscopic study.", "content": "The ultrastructural appearances in capillarosclerosis of the lower urinary tract in analgesic abuse are reported. The capillaries show thickened basement membranes consisting of numerous thin basement membrane lamellae. Between the newly formed basement membrane lamellae, masses of empty vacuoles (fat vacuoles) and a variety of membranous and vesicular structures are present. The pathogenesis of this alteration in the basement membrane is unknown. A common pathogenetic mechanism may be operative in the discoloration of renal papillae and mucous membranes of lower urinary tract on the one hand and capillarosclerosis on the other.", "contents": "Capillarosclerosis of the lower urinary tract in analgesic (phenacetin) abuse. An electron-microscopic study. The ultrastructural appearances in capillarosclerosis of the lower urinary tract in analgesic abuse are reported. The capillaries show thickened basement membranes consisting of numerous thin basement membrane lamellae. Between the newly formed basement membrane lamellae, masses of empty vacuoles (fat vacuoles) and a variety of membranous and vesicular structures are present. The pathogenesis of this alteration in the basement membrane is unknown. A common pathogenetic mechanism may be operative in the discoloration of renal papillae and mucous membranes of lower urinary tract on the one hand and capillarosclerosis on the other."} {"id": "PMID:153646", "title": "Ultrastructural cytology of human osteosarcoma cells.", "content": "The cytology of 6 osteosarcomas was examined by electron microscopy. In keeping with the varied pattern of osteosarcomas seen by light microscopy several types of tumor cells could be differentiated: osteoblast-like, fibroblast-like, chondroblast-like, osteoclast-like and histiocyte-like cells. Moreover, atypical malignant mesenchymal cells and vascular spaces were present. The individual cytoplasmic organelles are not considered to be specific to particular types of cell as seen from the discussion of the significance of rough endoplasmic reticulum, microfilaments and lysosomes. Only examination of the composite pattern of subcellular organelles allows the differentiation of certain cell types. All tumor cells visible in osteosarcomas are considered as modifications of a transformed common progenitor cell. Because of the variegated cytological picture a multipotent mesenchymal cell rather than an osteoblastic cell is assumed to be the ancestor cell.", "contents": "Ultrastructural cytology of human osteosarcoma cells. The cytology of 6 osteosarcomas was examined by electron microscopy. In keeping with the varied pattern of osteosarcomas seen by light microscopy several types of tumor cells could be differentiated: osteoblast-like, fibroblast-like, chondroblast-like, osteoclast-like and histiocyte-like cells. Moreover, atypical malignant mesenchymal cells and vascular spaces were present. The individual cytoplasmic organelles are not considered to be specific to particular types of cell as seen from the discussion of the significance of rough endoplasmic reticulum, microfilaments and lysosomes. Only examination of the composite pattern of subcellular organelles allows the differentiation of certain cell types. All tumor cells visible in osteosarcomas are considered as modifications of a transformed common progenitor cell. Because of the variegated cytological picture a multipotent mesenchymal cell rather than an osteoblastic cell is assumed to be the ancestor cell."} {"id": "PMID:153648", "title": "Experimental renal papillary necrosis in the rat: the selective vulnerability of medullary structures to injury.", "content": "Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Athough the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability or renal medullary structures to injury by the toxic agent studied.", "contents": "Experimental renal papillary necrosis in the rat: the selective vulnerability of medullary structures to injury. Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Athough the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability or renal medullary structures to injury by the toxic agent studied."} {"id": "PMID:153649", "title": "Involvement of the larynx in a congenital \"myopathy\", unilateral aplasia of the arytenoid, micrognathia, and malformation of the brain--a new syndrome?", "content": "Neuromyopathic changes were found in various limb muscles and in intrinsic laryngeal muscles of a two month old girl. She had been noted to have micrognathia, arthrogryposis and congenital stridor and died as a result of respiratory insufficiency and aspiration. Autopsy revealed an absent left arytenoid cartilage and severe histogenic abnormalities of the brain. Although the muscles involved showed a mainly myopathic pattern, marked signs of peripheral neurogenic involvement were present. These differed from motor neuron disease or aplasia of anterior horn cells. These findings cast a new light on the discussion of unclassified congenital myopathy resembling the picture of congenital muscular \"dystrophy\". This is the first case of congenital neuromyopathy in which involvement of intrinsic laryngeal muscles has been demonstrated morphologically.", "contents": "Involvement of the larynx in a congenital \"myopathy\", unilateral aplasia of the arytenoid, micrognathia, and malformation of the brain--a new syndrome? Neuromyopathic changes were found in various limb muscles and in intrinsic laryngeal muscles of a two month old girl. She had been noted to have micrognathia, arthrogryposis and congenital stridor and died as a result of respiratory insufficiency and aspiration. Autopsy revealed an absent left arytenoid cartilage and severe histogenic abnormalities of the brain. Although the muscles involved showed a mainly myopathic pattern, marked signs of peripheral neurogenic involvement were present. These differed from motor neuron disease or aplasia of anterior horn cells. These findings cast a new light on the discussion of unclassified congenital myopathy resembling the picture of congenital muscular \"dystrophy\". This is the first case of congenital neuromyopathy in which involvement of intrinsic laryngeal muscles has been demonstrated morphologically."} {"id": "PMID:153652", "title": "[Results of immunization of seronegative children with live poliomyelitis vaccine].", "content": "The humoral immunity status to poliomyelitis viruses was studied in a group of children under 3 years previously immunized at least 3 times with SLV incorporated into dragee-candy. A regular increase with age of the number of subjects possessing virus-neutralizaing antibody to poliomyelitis viruses was demonstrated, the incidence of antibody to the three virus types being distributed by age groups as follows: under 1 year -- 24%, 1 year -- 53%, 2 years -- 71.2%, 3 years -- 84.8%. The immune response in children was observed to begin developing after the first vaccination mainly to one virus type. Among the children of 1--3 years of age examined, 1.1% to 6.0% had no antibody to polioviruses. An attempt was made to induce antibody production in these children by an additional vaccination with liquid SLV monitoring the implantation of the vaccine virus in the intestinal tract and seroconversion in the blood. Consecutive administration of the oral liquid vaccine of national make was found to result in immune response in 100% of vaccinees.", "contents": "[Results of immunization of seronegative children with live poliomyelitis vaccine]. The humoral immunity status to poliomyelitis viruses was studied in a group of children under 3 years previously immunized at least 3 times with SLV incorporated into dragee-candy. A regular increase with age of the number of subjects possessing virus-neutralizaing antibody to poliomyelitis viruses was demonstrated, the incidence of antibody to the three virus types being distributed by age groups as follows: under 1 year -- 24%, 1 year -- 53%, 2 years -- 71.2%, 3 years -- 84.8%. The immune response in children was observed to begin developing after the first vaccination mainly to one virus type. Among the children of 1--3 years of age examined, 1.1% to 6.0% had no antibody to polioviruses. An attempt was made to induce antibody production in these children by an additional vaccination with liquid SLV monitoring the implantation of the vaccine virus in the intestinal tract and seroconversion in the blood. Consecutive administration of the oral liquid vaccine of national make was found to result in immune response in 100% of vaccinees."} {"id": "PMID:153657", "title": "[Sociological studies in acne vulgaris. 2. Effect of the disease on the evaluation of clinical picture and motivation for therapy].", "content": "A questionnaire was presented to 2009 18--19 year old recruitment candidates. The questionnaire enabled appraisal of antipathy towards patients with severe acne vulgaris and the occupational inpediment of severe acne. It was shown in comparison of patients with clinically relevant acne and healthy subjects or patients with a minor variant of acne that acne patients are more prepared to tolerate other acne patients than are healthy subjects. A questionnaire which enabled appraisal of attitudes to therapy was presented in addition to 351 patients with clinically relevant acne in this collective. The schools attended were also recorded in these patients. It was shown that the motivation to undergo treatment can be assumed in only half of the acne patients; this motivation is less the more radical the therapy. However, the motivation is greater the higher the educational level of the person questioned.", "contents": "[Sociological studies in acne vulgaris. 2. Effect of the disease on the evaluation of clinical picture and motivation for therapy]. A questionnaire was presented to 2009 18--19 year old recruitment candidates. The questionnaire enabled appraisal of antipathy towards patients with severe acne vulgaris and the occupational inpediment of severe acne. It was shown in comparison of patients with clinically relevant acne and healthy subjects or patients with a minor variant of acne that acne patients are more prepared to tolerate other acne patients than are healthy subjects. A questionnaire which enabled appraisal of attitudes to therapy was presented in addition to 351 patients with clinically relevant acne in this collective. The schools attended were also recorded in these patients. It was shown that the motivation to undergo treatment can be assumed in only half of the acne patients; this motivation is less the more radical the therapy. However, the motivation is greater the higher the educational level of the person questioned."} {"id": "PMID:153653", "title": "[Natural foci of viruses borne by Phlebotomus papatasi in the USSR according to a serologic study of the population].", "content": "Seven hundred sixteen blood serum specimens from residents of presumable foci of phlebotomus fevers in Turkmenia, Tajikistan, Uzbekistan, Azerbaijan, and Moldavia were examined by the neutralization, complement fixation, hemagglutionation-inhibition and indirect immunofluorescence tests for the presence of antibody to viruses of the group of phlebotomus fevers (Sicilyan, Neapolitan, and Karimabad) and to rhabdovirus isfahan transmitted by phlebotomus papatasi. For the first time, antibody to Karimabad and Isfahan viruses were found in residents of the Central Asian republics. Antibody to Sicilyan and Neapolitan fevers were found in residents of all the republics examined. Data have been obtained indicating probable pathogenicity of Isfahan virus for man.", "contents": "[Natural foci of viruses borne by Phlebotomus papatasi in the USSR according to a serologic study of the population]. Seven hundred sixteen blood serum specimens from residents of presumable foci of phlebotomus fevers in Turkmenia, Tajikistan, Uzbekistan, Azerbaijan, and Moldavia were examined by the neutralization, complement fixation, hemagglutionation-inhibition and indirect immunofluorescence tests for the presence of antibody to viruses of the group of phlebotomus fevers (Sicilyan, Neapolitan, and Karimabad) and to rhabdovirus isfahan transmitted by phlebotomus papatasi. For the first time, antibody to Karimabad and Isfahan viruses were found in residents of the Central Asian republics. Antibody to Sicilyan and Neapolitan fevers were found in residents of all the republics examined. Data have been obtained indicating probable pathogenicity of Isfahan virus for man."} {"id": "PMID:153660", "title": "Amino acid uptake by amino acid analog resistant tobacco cell lines.", "content": "Two tobacco cell lines resistant to p-fluorophenylalanine (PFP) and one resistant to 5-methyltryptophan (5-MT) are compared with wild type cells in their ability to absorb amino acids from the medium. One p-fluorophenylalanine-resistant cell line shows greatly reduced uptake of all amino acids so is resistant to growth inhibition by other amino acid analogs. The impaired absorption is noted with amino acids, amino acid analogs and shikimate, but not with cinnamate, salicylate, nicotine, glucose, 3-O-methylglucose and palmitate. The phenylalanine transport system of the PFP-resistant cell line and the wild type both have Km values of 90 micrograms, but have different Vmax values. Several analogs of phenylalanine and several neutral L-amino acids inihibt the phenylalanine transport system, while L-aspartic acid, L-arginine, D-phenylalanine or chlorogenic acid do not interfere with the L-phenylalanine uptake. The results indicate the presence of more than one transport system for amino acid uptake. The lessened uptake of all amino acids, the specificity of the uptake systems and the unchanged binding let us conclude that a pleiotropic mutation or that some inhibitor causes the reduced uptake of all amino acids by the PFP-resistant cell line.", "contents": "Amino acid uptake by amino acid analog resistant tobacco cell lines. Two tobacco cell lines resistant to p-fluorophenylalanine (PFP) and one resistant to 5-methyltryptophan (5-MT) are compared with wild type cells in their ability to absorb amino acids from the medium. One p-fluorophenylalanine-resistant cell line shows greatly reduced uptake of all amino acids so is resistant to growth inhibition by other amino acid analogs. The impaired absorption is noted with amino acids, amino acid analogs and shikimate, but not with cinnamate, salicylate, nicotine, glucose, 3-O-methylglucose and palmitate. The phenylalanine transport system of the PFP-resistant cell line and the wild type both have Km values of 90 micrograms, but have different Vmax values. Several analogs of phenylalanine and several neutral L-amino acids inihibt the phenylalanine transport system, while L-aspartic acid, L-arginine, D-phenylalanine or chlorogenic acid do not interfere with the L-phenylalanine uptake. The results indicate the presence of more than one transport system for amino acid uptake. The lessened uptake of all amino acids, the specificity of the uptake systems and the unchanged binding let us conclude that a pleiotropic mutation or that some inhibitor causes the reduced uptake of all amino acids by the PFP-resistant cell line."} {"id": "PMID:153661", "title": "Evidence for distinct amino acid transport systems in cultured tobacco cells.", "content": "It is shown by competition experiments that tobacco cell lines have distinct transport systems for L-amino acids. For all tested amino acids the Lineweaver-Burk plots were diphasic indicating the presence of more than one carrier for any one amino acid. Moreover distinct transport systems for neutral, acidic and basic amino acids were kinetically characterized. Based on competition experiments neutral amino acids were absorbed by all transport systems. Aspartic acid entered the cells via its own carrier and via the basic carrier while arginine was taken up only by the basic carrier. Neutral amino acids such as L-leucine or L-phenylalanine were taken up faster than acidic or basic amino acids.", "contents": "Evidence for distinct amino acid transport systems in cultured tobacco cells. It is shown by competition experiments that tobacco cell lines have distinct transport systems for L-amino acids. For all tested amino acids the Lineweaver-Burk plots were diphasic indicating the presence of more than one carrier for any one amino acid. Moreover distinct transport systems for neutral, acidic and basic amino acids were kinetically characterized. Based on competition experiments neutral amino acids were absorbed by all transport systems. Aspartic acid entered the cells via its own carrier and via the basic carrier while arginine was taken up only by the basic carrier. Neutral amino acids such as L-leucine or L-phenylalanine were taken up faster than acidic or basic amino acids."} {"id": "PMID:153662", "title": "[The carcinogenic effect of polycyclic aromatic hydrocarbons (author's transl)].", "content": "The two most important theories on the mode of action of carcinogenic hydrocarbons are juxtaposed by a new theory. This theory refers to ideas which have been discussed for a rather long time in silicose research and describes a mechanism whose principle will possibly be important for the specific effect of some pharmaceutica.", "contents": "[The carcinogenic effect of polycyclic aromatic hydrocarbons (author's transl)]. The two most important theories on the mode of action of carcinogenic hydrocarbons are juxtaposed by a new theory. This theory refers to ideas which have been discussed for a rather long time in silicose research and describes a mechanism whose principle will possibly be important for the specific effect of some pharmaceutica."} {"id": "PMID:153663", "title": "Ribonuclease A digestion by proteinase K.", "content": "The digestion of ribonuclease A by proteinase K yielded one major degradation product only, which could not be distinguished from ribonuclease S by electrophoretical and immunological methods. This component (ribonuclease K) possessing full catalytic activity was characterized to be (1--20/21--124) ribonuclease A. Combined action of proteinase K and trypsin on ribonuclease A leads to a significant increase of the inactivation rate which may be useful in the isolation of mRNA from polysomes.", "contents": "Ribonuclease A digestion by proteinase K. The digestion of ribonuclease A by proteinase K yielded one major degradation product only, which could not be distinguished from ribonuclease S by electrophoretical and immunological methods. This component (ribonuclease K) possessing full catalytic activity was characterized to be (1--20/21--124) ribonuclease A. Combined action of proteinase K and trypsin on ribonuclease A leads to a significant increase of the inactivation rate which may be useful in the isolation of mRNA from polysomes."} {"id": "PMID:153664", "title": "[Phosphoenolpyruvate carboxykinase in Phycomyces blakesleeanus Bgff. (author's transl)].", "content": "Phosphoenolpyruvate carboxykinase (PEPCK) from Phycomyces blakesleeanus was partially purified by protamine sulfate precipitation, ammoniumsulfate precipitation, and diethylamino ethyl cellulose (DEAE) treatment. This preparation was employed for the characterization of the enzyme. The Km values for phosphoenolpyruvate (PEP) and ADP were determined as 1.6 and 0.42 mM. The nucleotid specificity was demonstrated for ADP exclusively. The use of sulfuryl reagents showed the presence of thiol groups sensitive against p-hydroxymercuribenzoate but not effected by N-ethylmaleimide.", "contents": "[Phosphoenolpyruvate carboxykinase in Phycomyces blakesleeanus Bgff. (author's transl)]. Phosphoenolpyruvate carboxykinase (PEPCK) from Phycomyces blakesleeanus was partially purified by protamine sulfate precipitation, ammoniumsulfate precipitation, and diethylamino ethyl cellulose (DEAE) treatment. This preparation was employed for the characterization of the enzyme. The Km values for phosphoenolpyruvate (PEP) and ADP were determined as 1.6 and 0.42 mM. The nucleotid specificity was demonstrated for ADP exclusively. The use of sulfuryl reagents showed the presence of thiol groups sensitive against p-hydroxymercuribenzoate but not effected by N-ethylmaleimide."} {"id": "PMID:153665", "title": "The mutagenicity of dichloroacetaldehyde.", "content": "Dichloroacetaldehyde, a presumed metabolite of the insecticides dichlorvos and trichlorphon, is mutagenic in the Salmonella/microsome test. Its mutagenic potency is higher than that of the established mutagen dichlorvos. It is possible that the bacterial mutagenicity test only or mainly detects the effect of methylation by dichlorvos.", "contents": "The mutagenicity of dichloroacetaldehyde. Dichloroacetaldehyde, a presumed metabolite of the insecticides dichlorvos and trichlorphon, is mutagenic in the Salmonella/microsome test. Its mutagenic potency is higher than that of the established mutagen dichlorvos. It is possible that the bacterial mutagenicity test only or mainly detects the effect of methylation by dichlorvos."} {"id": "PMID:153666", "title": "Physical parameters and possible regulation of zeta-aminolevulinic acid synthetase.", "content": "Physical measurements were made on the zeta-aminolevulinic acid synthetase from Rhodopseudomonas spheroides. These include a Stokes radius of 3.8 nm, determined by gel filtration, and sedimentation coefficient of 5.46 S by sucrose density gradient centrifugation. From these measurements and the value of partial specific volume of 0.732 ml/g determined from the amino acid composition, the following physical constants were calculated: molecular weight, 88000; diffusion coefficient, 5.65 X 10(-7) cm2s-1; frictional ratio, 1.30; axial ratio, 5.0. The enzyme is inhibited by more than 50% by glyceraldehyde 3-phosphate (1mM), pyruvate (0.02 M), alpha-ketoglutarate (0.02 M), urea (0.8 M), CoCl2 (0.2 mM) and hemin (5 micrograms). The effect of these inhibitors on the possible regulation of this enzymic activity is discussed.", "contents": "Physical parameters and possible regulation of zeta-aminolevulinic acid synthetase. Physical measurements were made on the zeta-aminolevulinic acid synthetase from Rhodopseudomonas spheroides. These include a Stokes radius of 3.8 nm, determined by gel filtration, and sedimentation coefficient of 5.46 S by sucrose density gradient centrifugation. From these measurements and the value of partial specific volume of 0.732 ml/g determined from the amino acid composition, the following physical constants were calculated: molecular weight, 88000; diffusion coefficient, 5.65 X 10(-7) cm2s-1; frictional ratio, 1.30; axial ratio, 5.0. The enzyme is inhibited by more than 50% by glyceraldehyde 3-phosphate (1mM), pyruvate (0.02 M), alpha-ketoglutarate (0.02 M), urea (0.8 M), CoCl2 (0.2 mM) and hemin (5 micrograms). The effect of these inhibitors on the possible regulation of this enzymic activity is discussed."} {"id": "PMID:153667", "title": "Lysine as the substrate binding site of porphobilinogen synthase of Rhodopseudomonas spheroides.", "content": "The 14C labelled inactive protein obtained by sodium borohydride reduction of the enzyme, porphobilinogen synthase of Rhodopseudomonas spheroides, in the presence of [4-14C]5-aminolevulinic acid, gave on acid hydrolysis and subsequent electrophoresis or two-dimensional chromatography a major radioactive spot which was confirmed to be N-epsilon-[4-(-5aminovaleric acid)]lysine (ALA-lysine) by comparing its co-chromatographic and electrophoretic behaviour with the chemically synthesized ALA-lysine. An epsilon-NH2 group of lysine residue of porphobilinogen synthase, is thus the binding site of the substrate, 5-aminolevulinic acid.", "contents": "Lysine as the substrate binding site of porphobilinogen synthase of Rhodopseudomonas spheroides. The 14C labelled inactive protein obtained by sodium borohydride reduction of the enzyme, porphobilinogen synthase of Rhodopseudomonas spheroides, in the presence of [4-14C]5-aminolevulinic acid, gave on acid hydrolysis and subsequent electrophoresis or two-dimensional chromatography a major radioactive spot which was confirmed to be N-epsilon-[4-(-5aminovaleric acid)]lysine (ALA-lysine) by comparing its co-chromatographic and electrophoretic behaviour with the chemically synthesized ALA-lysine. An epsilon-NH2 group of lysine residue of porphobilinogen synthase, is thus the binding site of the substrate, 5-aminolevulinic acid."} {"id": "PMID:153668", "title": "Quantification and localisation of SH-groups in human blood serum proteins.", "content": "The thiol groups of human blood serum proteins were determined after 24 hours interaction with dithionitrobenzoic-acid (DTNB) to an average of 538 +/- 60 mumol/l serum. After treatment of the serum with [35S]DTNB, autoradiograms of the protein elpherograms revealed two main peaks: The first with 63% of total activity, in the albumin region, corresponding to 0.60 SH/mol, the second with 23% of total activity, in the gamma-globulin range, corresponding to 2.2 SH/mol. After 30 minutes incubation with DTNB, or with p-chloromercuribenzoate (CMB), in freshly prepared pools of IgG only 0.2 SH/mol were found which is the expected value already known from the literature. Autoradiograms taken from serum protein elpherograms after interaction with [14C]CMB only show the main SH-peak in the albumin range. Thus it is concluded that the SH-peak in the gamma-globulin region after 24 hours incubation with [35S]DTNB is due to one highly labile S-S-bond which easily undergoes a disulfide exchange with DTNB.", "contents": "Quantification and localisation of SH-groups in human blood serum proteins. The thiol groups of human blood serum proteins were determined after 24 hours interaction with dithionitrobenzoic-acid (DTNB) to an average of 538 +/- 60 mumol/l serum. After treatment of the serum with [35S]DTNB, autoradiograms of the protein elpherograms revealed two main peaks: The first with 63% of total activity, in the albumin region, corresponding to 0.60 SH/mol, the second with 23% of total activity, in the gamma-globulin range, corresponding to 2.2 SH/mol. After 30 minutes incubation with DTNB, or with p-chloromercuribenzoate (CMB), in freshly prepared pools of IgG only 0.2 SH/mol were found which is the expected value already known from the literature. Autoradiograms taken from serum protein elpherograms after interaction with [14C]CMB only show the main SH-peak in the albumin range. Thus it is concluded that the SH-peak in the gamma-globulin region after 24 hours incubation with [35S]DTNB is due to one highly labile S-S-bond which easily undergoes a disulfide exchange with DTNB."} {"id": "PMID:153669", "title": "Host factors involved in the growth of microvirid phage alpha 3.", "content": "Host factors involed in the growth of microvirid phage alpha3 were determined using various replication mutants of Escherichia coli. The viral multiplication was dependent on functional products of dnaE, dnaF(NRDA), DNAG, and dnaZ genes. Host functions directed by dnaA, so-alled dnaH, dnaI, and dnaP genes were dispensable for the viral growth. In contrast with phiZ174 and G4, alpha3 would grow sufficiently In dnaB and dnaC(D) mutants. The viral growth was not significantly affected by host polAts, seg, and groPC mutations.", "contents": "Host factors involved in the growth of microvirid phage alpha 3. Host factors involed in the growth of microvirid phage alpha3 were determined using various replication mutants of Escherichia coli. The viral multiplication was dependent on functional products of dnaE, dnaF(NRDA), DNAG, and dnaZ genes. Host functions directed by dnaA, so-alled dnaH, dnaI, and dnaP genes were dispensable for the viral growth. In contrast with phiZ174 and G4, alpha3 would grow sufficiently In dnaB and dnaC(D) mutants. The viral growth was not significantly affected by host polAts, seg, and groPC mutations."} {"id": "PMID:153676", "title": "[Management of the work place. Erogonomics and occupational medicine for the benefit of prevention].", "content": "Between the state of well-being and that of illness, an intermediary state often occurs, characterized by feelings of uneasiness, fatigue and pains. The study of these intermediary states in function of the work load (posture, noises, heat, etc.) constitutes an important feature of ergonomics. In this study we present the results of two polls showing pains due to inappropriate postures. Many observations of occupational medicine lead us to believe that pathological troubles of rheumatic order (arthritis, periathritis, tendinitis, myalgias, arthroses) can appear as a result of inappropriate postures and repetitive movements over a number of years. Thus, the ergonomic analysis of the work place can help to determine the risk of illness.", "contents": "[Management of the work place. Erogonomics and occupational medicine for the benefit of prevention]. Between the state of well-being and that of illness, an intermediary state often occurs, characterized by feelings of uneasiness, fatigue and pains. The study of these intermediary states in function of the work load (posture, noises, heat, etc.) constitutes an important feature of ergonomics. In this study we present the results of two polls showing pains due to inappropriate postures. Many observations of occupational medicine lead us to believe that pathological troubles of rheumatic order (arthritis, periathritis, tendinitis, myalgias, arthroses) can appear as a result of inappropriate postures and repetitive movements over a number of years. Thus, the ergonomic analysis of the work place can help to determine the risk of illness."} {"id": "PMID:153677", "title": "[Insurance and preventive medicine].", "content": "Not only do insurance companies have to pay in case of death, injuries or disease, they are also concerned with their prevention. This is particularly true for the \"Swiss National Accident Insurance Fund\" (Caisse nationale suisse d'assurance en cas d'accidents--(CNA): for them the prevention of work related accidents and occupational diseases is required by law. Preventive activities in this area are very promising. The progress in the sickness insurance programmes for preventive medicine in the general population has, however, not been as successful. To date, the legislation denies payment for preventive medical care. Why is there this difference? In the case of accidents and occupational diseases, the cause of the pathologies are for the most part exogenous and develop in well known and controlled environments. In the case of disease or invalidity in the general population, the factors are in a large part endogenous and therefore very difficult to supervise, as they develop in much more complex and uncontrolled environments. Nevertheless progress has been done in this field as well. At present, some selected scientifically proven preventive examinations could be included in insurance programmes as part of a general plan and with strict quality control of laboratory findings.", "contents": "[Insurance and preventive medicine]. Not only do insurance companies have to pay in case of death, injuries or disease, they are also concerned with their prevention. This is particularly true for the \"Swiss National Accident Insurance Fund\" (Caisse nationale suisse d'assurance en cas d'accidents--(CNA): for them the prevention of work related accidents and occupational diseases is required by law. Preventive activities in this area are very promising. The progress in the sickness insurance programmes for preventive medicine in the general population has, however, not been as successful. To date, the legislation denies payment for preventive medical care. Why is there this difference? In the case of accidents and occupational diseases, the cause of the pathologies are for the most part exogenous and develop in well known and controlled environments. In the case of disease or invalidity in the general population, the factors are in a large part endogenous and therefore very difficult to supervise, as they develop in much more complex and uncontrolled environments. Nevertheless progress has been done in this field as well. At present, some selected scientifically proven preventive examinations could be included in insurance programmes as part of a general plan and with strict quality control of laboratory findings."} {"id": "PMID:153680", "title": "[Immunologic donor-recipient matching in living kidney transplantation].", "content": "The better results of transplantation in kidneys of relatives in contrast to cadaveric kidneys are above all traced back to a compatibility in the HLA-D-Locus which is more frequently present in relatives and which can be established by a lacking stimulation in the mixed culture of lymphocytes. Therefore, the selection of donor and recipient in transplantations of living kidneys where there is no pressure of time should apart from the serological standardization of lymphocytes should also comprise the mixed culture of lymphocytes lasting 5 to 7 days.", "contents": "[Immunologic donor-recipient matching in living kidney transplantation]. The better results of transplantation in kidneys of relatives in contrast to cadaveric kidneys are above all traced back to a compatibility in the HLA-D-Locus which is more frequently present in relatives and which can be established by a lacking stimulation in the mixed culture of lymphocytes. Therefore, the selection of donor and recipient in transplantations of living kidneys where there is no pressure of time should apart from the serological standardization of lymphocytes should also comprise the mixed culture of lymphocytes lasting 5 to 7 days."} {"id": "PMID:153678", "title": "[Animal experiment studies on the effect of intra-articular injections of antiphlogistic-antirheumatic agents on articular cartilage in vivo].", "content": "Animal experiments have shown that weekly intraarticular injections of various antiphlogistic/antirheumatic drugs into the knee joint induce progressive degenerative alterations in joint cartilage. The observed degenerations and destructions are most similar to the pathophysiology of osteoarthrosis in humans. By X-ray and macroscopic techniques the degenerative processes can be studied qualitatively and quantitatively. A decrease of joint space is a sensitive and early indicator of osteoarthrosis and showed that 10 weeks after intraarticular application of Ibuprofen, Phenylbutazone, Oxyphenbutazone, Flufenamic acid, Niflumic acid, Na-salicylate, Clofezone, Bumadizone and Dexamethasone the degenerative alterations in the injected knee joints were more severe than by applications of Chloroquine,D-penicillamine, Salicylamide and Indometacin. The degenerative effect on articular cartilage by the investigated drugs can be explained by their inhibitory potency on anabolic metabolism of connective tissue. The results of our animal experiments lead to the conclusion, that antiinflammatory drugs may also in man induce or accelerate degenerative joint diseases especially after long term treatment with high doses of these drugs.", "contents": "[Animal experiment studies on the effect of intra-articular injections of antiphlogistic-antirheumatic agents on articular cartilage in vivo]. Animal experiments have shown that weekly intraarticular injections of various antiphlogistic/antirheumatic drugs into the knee joint induce progressive degenerative alterations in joint cartilage. The observed degenerations and destructions are most similar to the pathophysiology of osteoarthrosis in humans. By X-ray and macroscopic techniques the degenerative processes can be studied qualitatively and quantitatively. A decrease of joint space is a sensitive and early indicator of osteoarthrosis and showed that 10 weeks after intraarticular application of Ibuprofen, Phenylbutazone, Oxyphenbutazone, Flufenamic acid, Niflumic acid, Na-salicylate, Clofezone, Bumadizone and Dexamethasone the degenerative alterations in the injected knee joints were more severe than by applications of Chloroquine,D-penicillamine, Salicylamide and Indometacin. The degenerative effect on articular cartilage by the investigated drugs can be explained by their inhibitory potency on anabolic metabolism of connective tissue. The results of our animal experiments lead to the conclusion, that antiinflammatory drugs may also in man induce or accelerate degenerative joint diseases especially after long term treatment with high doses of these drugs."} {"id": "PMID:153679", "title": "Comparison of clofezone and diclofenac in the treatment of out-patients suffering from activated (painful) osteoarthrosis.", "content": "The effectiveness and acceptability of clofezone (Perclusone) were compared with those of diclofenac in a placebo-controlled, double-blind, cross-over trial on a group of 29 out-patients suffering from osteoarthrosis of the knee or hip. Clofezone was given at a daily dosage of 1200 mg during the first week and 600 mg during the second week; the corresponding dosages of diclofenac were 150 mg and 75 mg. The duration of the trial was 6 weeks. In order to wash out previous medication, a placebo was given for one week before and after each medication period. Eight of the patients stopped taking their drug after 1--3 weeks, namely 5 in the clofezone group and 3 in the diclofenac group, while one patient stopped taking the placebo. The principal reason for these stoppages was gastrointestinal intolerance. These 9 patients were disregarded in the evaluation of the trial results. This evaluation on the remaining 20 patients showed that clofezone brought about a significant improvement in respect of pain (both at rest and during movement), inflammation and mobility after two weeks' application. In the diclofenac group the only significant improvement after the same period was in respect of pain during movement. Statistical comparison of the two groups showed that the reduction in pain during movement and in inflammation was significantly greater under clofezone than under diclofenac and that clofezone had the longer-lasting action. These findings are discussed in the light of the kinetic characteristics of the two drugs and of the mild antidepressant properties of clofezone. There was no significant difference between the two drugs as regards tolerance.", "contents": "Comparison of clofezone and diclofenac in the treatment of out-patients suffering from activated (painful) osteoarthrosis. The effectiveness and acceptability of clofezone (Perclusone) were compared with those of diclofenac in a placebo-controlled, double-blind, cross-over trial on a group of 29 out-patients suffering from osteoarthrosis of the knee or hip. Clofezone was given at a daily dosage of 1200 mg during the first week and 600 mg during the second week; the corresponding dosages of diclofenac were 150 mg and 75 mg. The duration of the trial was 6 weeks. In order to wash out previous medication, a placebo was given for one week before and after each medication period. Eight of the patients stopped taking their drug after 1--3 weeks, namely 5 in the clofezone group and 3 in the diclofenac group, while one patient stopped taking the placebo. The principal reason for these stoppages was gastrointestinal intolerance. These 9 patients were disregarded in the evaluation of the trial results. This evaluation on the remaining 20 patients showed that clofezone brought about a significant improvement in respect of pain (both at rest and during movement), inflammation and mobility after two weeks' application. In the diclofenac group the only significant improvement after the same period was in respect of pain during movement. Statistical comparison of the two groups showed that the reduction in pain during movement and in inflammation was significantly greater under clofezone than under diclofenac and that clofezone had the longer-lasting action. These findings are discussed in the light of the kinetic characteristics of the two drugs and of the mild antidepressant properties of clofezone. There was no significant difference between the two drugs as regards tolerance."} {"id": "PMID:153690", "title": "[Surgical management of abdominal-wall insufficiency in the female (report on 94 cases)].", "content": "A clinical report is given on 94 cases of operative reconstruction of the anterior abdominal wall. There are medical and cosmetic indications. The morphological and functional results of these operations are good. Attending to the contraindications the number of dangerous complications in the postoperative course is low. No case of death was seen.", "contents": "[Surgical management of abdominal-wall insufficiency in the female (report on 94 cases)]. A clinical report is given on 94 cases of operative reconstruction of the anterior abdominal wall. There are medical and cosmetic indications. The morphological and functional results of these operations are good. Attending to the contraindications the number of dangerous complications in the postoperative course is low. No case of death was seen."} {"id": "PMID:153692", "title": "Comparative toxicity of trivalent and hexavalent chromium to rabbits. III. Biochemical and histological changes in testicular tissue.", "content": "The administration of trivalent and hexavalent chromium compounds produced inhibition of the activity of succinic dehydrogenase, adenosine triphosphatase and acid phosphattase accompanied by cellular degeneration with complete absence of spermatocytes in the testis of rabbits. The biochemical and histological changes were more marked in the animals treated with the trivalent chromium than those exposed to hexavalent chromium and were progressive with the duration of exposure.", "contents": "Comparative toxicity of trivalent and hexavalent chromium to rabbits. III. Biochemical and histological changes in testicular tissue. The administration of trivalent and hexavalent chromium compounds produced inhibition of the activity of succinic dehydrogenase, adenosine triphosphatase and acid phosphattase accompanied by cellular degeneration with complete absence of spermatocytes in the testis of rabbits. The biochemical and histological changes were more marked in the animals treated with the trivalent chromium than those exposed to hexavalent chromium and were progressive with the duration of exposure."} {"id": "PMID:153693", "title": "[Small-angle scattering of the quaternary structure of phosphofructokinase from baker's yeast].", "content": "The phosphofructokinase (E.C. 2.7.1.11) from baker's yeast was examined by means of small angle X-ray scattering in 0.1 M K-phosphate buffer, pH 7. A quaternary structure model was obtained from the comparison of the model scattering curve with the experimental one. The eight subunits of the yeast phosphofructokinase are arranged in a D2-symmetry. The proposed scattering equivalent model corresponds to a structural description with a resolution of 2.5 nm. Models with a C8-symmetry and D4-symmetry can be ruled out.", "contents": "[Small-angle scattering of the quaternary structure of phosphofructokinase from baker's yeast]. The phosphofructokinase (E.C. 2.7.1.11) from baker's yeast was examined by means of small angle X-ray scattering in 0.1 M K-phosphate buffer, pH 7. A quaternary structure model was obtained from the comparison of the model scattering curve with the experimental one. The eight subunits of the yeast phosphofructokinase are arranged in a D2-symmetry. The proposed scattering equivalent model corresponds to a structural description with a resolution of 2.5 nm. Models with a C8-symmetry and D4-symmetry can be ruled out."} {"id": "PMID:153694", "title": "Relationships between association state and enzymic activity of human erythrocyte phosphofructokinase.", "content": "Human erythrocyte phosphofructokinase has been subjected to active band centrifugation and stability measurements over a broad range of conditions. The enzyme behaves differently in-Tris buffer containing ATP and phosphate buffer containing fructose 6-phosphate. In the first buffer, dissociation is favoured and after prolonged storage of the enzyme tetramers represent the highest state of association. At 4 degrees C the enzyme exhibits the phenomenon of reversible cold-inactivation. This property is attributed to slow dissociation of the active associated states of the enzyme to dimers. The cold-inactivated enzyme can be reactivated by fructose 1,6-bisphosphate. Inorganic phosphate and fructose 6-phosphate have been found to protect the enzyme from cold-inactivation. Under these conditions, the sedimentation coefficient and the specific activity depend on the enzyme concentration only. The specific activity does not change on storage of the diluted enzyme at 4 degrees C. At 20 degrees C, however, a slow activation proceeds during incubation of the diluted enzyme. The correlations between the association state and the enzymic activity are discussed.", "contents": "Relationships between association state and enzymic activity of human erythrocyte phosphofructokinase. Human erythrocyte phosphofructokinase has been subjected to active band centrifugation and stability measurements over a broad range of conditions. The enzyme behaves differently in-Tris buffer containing ATP and phosphate buffer containing fructose 6-phosphate. In the first buffer, dissociation is favoured and after prolonged storage of the enzyme tetramers represent the highest state of association. At 4 degrees C the enzyme exhibits the phenomenon of reversible cold-inactivation. This property is attributed to slow dissociation of the active associated states of the enzyme to dimers. The cold-inactivated enzyme can be reactivated by fructose 1,6-bisphosphate. Inorganic phosphate and fructose 6-phosphate have been found to protect the enzyme from cold-inactivation. Under these conditions, the sedimentation coefficient and the specific activity depend on the enzyme concentration only. The specific activity does not change on storage of the diluted enzyme at 4 degrees C. At 20 degrees C, however, a slow activation proceeds during incubation of the diluted enzyme. The correlations between the association state and the enzymic activity are discussed."} {"id": "PMID:153695", "title": "Association behaviour of human erythrocyte phosphofructokinase. Dependence of molecular weight on enzyme concentration as analyzed by frontal gel chromatography.", "content": "Self-association of human erythrocyte phosphofructokinase has been studied at pH 8.0 and at 4 degrees C in the presence of 2 mM fructose 6-phosphate by means of frontal gel chromatography. Under these conditions the basic associating catalytically active species is the tetramer of the enzyme with a molecular weight of about 330000, the monomers of which having a molecular weight of 83000 as determined by sodium dodecyl sulphate electrophoresis. The experimental data have been compared with various models describing the enzyme association. The mode of association can sufficiently be described by assuming a weakly negative cooperative process in which the association constant of the nucleation step (association of two tetramers to an octamer) is larger than that of the following propagation steps. The geometry of association appears to be approximately spherical.", "contents": "Association behaviour of human erythrocyte phosphofructokinase. Dependence of molecular weight on enzyme concentration as analyzed by frontal gel chromatography. Self-association of human erythrocyte phosphofructokinase has been studied at pH 8.0 and at 4 degrees C in the presence of 2 mM fructose 6-phosphate by means of frontal gel chromatography. Under these conditions the basic associating catalytically active species is the tetramer of the enzyme with a molecular weight of about 330000, the monomers of which having a molecular weight of 83000 as determined by sodium dodecyl sulphate electrophoresis. The experimental data have been compared with various models describing the enzyme association. The mode of association can sufficiently be described by assuming a weakly negative cooperative process in which the association constant of the nucleation step (association of two tetramers to an octamer) is larger than that of the following propagation steps. The geometry of association appears to be approximately spherical."} {"id": "PMID:153696", "title": "[Granulocyte chalone: tissue specificity of action in short-term cultures].", "content": "Granulocytic chalone containing extracts were obtained by incubating rat bone marrow cells in Hanks salt solution and further purification of the conditioned medium by ultrafiltration and gel chromatography. These extracts cause specific inhibition of 3H-thymidine incorporation in short-term cultures of rat bone marrow and murine myeloic leukemias. Ehrlich ascites tumour, spleen (mouse), lymphatic leukemia L1210 and melanoma AMel 3 (hamster) are not influenced under identical experimental conditions. Comparing the action of cell proliferation inhibitors (chalones) from Ehrlich ascites tumour and spleen lymphocytes it was shown that inhibition of 3H-thymidine incorporation occurs only with those cells corresponding to the origin of the inhibitor. Therefore, the described short-term cultures seem to be suitable for testing the tissue specificity of action, as the main criterion for authenticity of the chalone effect, at least in the case of granulocytic chalone.", "contents": "[Granulocyte chalone: tissue specificity of action in short-term cultures]. Granulocytic chalone containing extracts were obtained by incubating rat bone marrow cells in Hanks salt solution and further purification of the conditioned medium by ultrafiltration and gel chromatography. These extracts cause specific inhibition of 3H-thymidine incorporation in short-term cultures of rat bone marrow and murine myeloic leukemias. Ehrlich ascites tumour, spleen (mouse), lymphatic leukemia L1210 and melanoma AMel 3 (hamster) are not influenced under identical experimental conditions. Comparing the action of cell proliferation inhibitors (chalones) from Ehrlich ascites tumour and spleen lymphocytes it was shown that inhibition of 3H-thymidine incorporation occurs only with those cells corresponding to the origin of the inhibitor. Therefore, the described short-term cultures seem to be suitable for testing the tissue specificity of action, as the main criterion for authenticity of the chalone effect, at least in the case of granulocytic chalone."} {"id": "PMID:153698", "title": "Achilles tendon injury. II. Structure of tenotomized rabbit crural muscles after primary and delayed tendon suture.", "content": "This investigation was designed to study the long-term effects of surgical treatment, as recommended and followed in clinical practice, on the fine structure of rabbit crural muscles after Achilles tenotomy. Two main results were made: (A) Even after 12 weeks of mobilization a number of morphological changes were found, especially in the soleus muscles. These abnormalities were similar to those found in human soleus muscles after surgically treated Achilles tendon rupture. (B) There were a large number of small heavily stained (for myofibrillar ATPase at pH 9.4) fibres in the experimental soleus muscles, such that the normal ratio of fibre types was reversed. This was apparent if tendon suture had been performed after a delay of 3 weeks. The results suggested that as a consequence of the de- and regenerative events, induced by immobilization or tenotomy plus immobilization, a number of new fibres had been formed. Some of these were so short that they were out of reach of nerve terminals and remained non-innervated. Furthermore, from the point of view of clinical practice, the extensive long-term effects of suture delay make themselves manifest not until at least a delay of one week.", "contents": "Achilles tendon injury. II. Structure of tenotomized rabbit crural muscles after primary and delayed tendon suture. This investigation was designed to study the long-term effects of surgical treatment, as recommended and followed in clinical practice, on the fine structure of rabbit crural muscles after Achilles tenotomy. Two main results were made: (A) Even after 12 weeks of mobilization a number of morphological changes were found, especially in the soleus muscles. These abnormalities were similar to those found in human soleus muscles after surgically treated Achilles tendon rupture. (B) There were a large number of small heavily stained (for myofibrillar ATPase at pH 9.4) fibres in the experimental soleus muscles, such that the normal ratio of fibre types was reversed. This was apparent if tendon suture had been performed after a delay of 3 weeks. The results suggested that as a consequence of the de- and regenerative events, induced by immobilization or tenotomy plus immobilization, a number of new fibres had been formed. Some of these were so short that they were out of reach of nerve terminals and remained non-innervated. Furthermore, from the point of view of clinical practice, the extensive long-term effects of suture delay make themselves manifest not until at least a delay of one week."} {"id": "PMID:153699", "title": "The behaviour of some enzymes in the mouse liver due to chronic benzene intoxication.", "content": "1. Long trem benzene action brings about a permanent decrease in oxidoreductive enzymes and active transport as well as an inactivation of the lysosomal apparatus in liver-cells. 2. Particular liver lobule zones show different sensitivity to toxic action of benzene which might result from their different role in the processes of benzene biotransformation.", "contents": "The behaviour of some enzymes in the mouse liver due to chronic benzene intoxication. 1. Long trem benzene action brings about a permanent decrease in oxidoreductive enzymes and active transport as well as an inactivation of the lysosomal apparatus in liver-cells. 2. Particular liver lobule zones show different sensitivity to toxic action of benzene which might result from their different role in the processes of benzene biotransformation."} {"id": "PMID:153700", "title": "Electron microscopic localization of Mg2+ -dependent adenosine triphosphatase activity in the amphibian pancreas (Salamandra salamandra L. and Rana esculenta L.).", "content": "The ultrastructural distribution of Mg2+ -dependent adenosine triphosphatase (ATPase) activity has been investigated in the salamander and frog pancreas by using glutaraldehyde fixations and a modified Wachstein-Meisel reaction medium. In both species the reaction product (lead phosphate) was found associated with the plasma membrane external side of all islet cell types (B-, A- and D-cells) and of acinar and ductular/centro-acinar cells. Except the apical pole of salamander acinar and centro-acinar cells, usually devoid of reaction, no preferential distribution of enzyme activity depending on endocrine or exocrine cell aspects could be observed. Other specific enzyme localizations included the mitochondria matrices, nucleoles, condensed nuclear chromatin, periaxolemmal spaces in nerve bundles and sometimes the cleft of neuro-glandular junctions. The occurrence of reaction deposits in connective tissue, in the cytoplasm of both islet and exocrine cells and in the nerve fiber axoplasm was considered as a possible diffusion artifact. The reaction intensity, but not its distribution, varied sensibly with the incubation period. 2-iodoacetamide and p-chlormercuribenzoic acid decreased the amount of reaction deposits at the level of all reactive sites and especially in mitochondria. The specificity of Mg2+ -ATPase demonstration in this paper is analysed taking into account several inherent shortcomings of the Wachstein-Meisel incubation medium and of the fixative. The different enzyme localizations, as well as their functional significances are discussed in relation with the findings of other authors.", "contents": "Electron microscopic localization of Mg2+ -dependent adenosine triphosphatase activity in the amphibian pancreas (Salamandra salamandra L. and Rana esculenta L.). The ultrastructural distribution of Mg2+ -dependent adenosine triphosphatase (ATPase) activity has been investigated in the salamander and frog pancreas by using glutaraldehyde fixations and a modified Wachstein-Meisel reaction medium. In both species the reaction product (lead phosphate) was found associated with the plasma membrane external side of all islet cell types (B-, A- and D-cells) and of acinar and ductular/centro-acinar cells. Except the apical pole of salamander acinar and centro-acinar cells, usually devoid of reaction, no preferential distribution of enzyme activity depending on endocrine or exocrine cell aspects could be observed. Other specific enzyme localizations included the mitochondria matrices, nucleoles, condensed nuclear chromatin, periaxolemmal spaces in nerve bundles and sometimes the cleft of neuro-glandular junctions. The occurrence of reaction deposits in connective tissue, in the cytoplasm of both islet and exocrine cells and in the nerve fiber axoplasm was considered as a possible diffusion artifact. The reaction intensity, but not its distribution, varied sensibly with the incubation period. 2-iodoacetamide and p-chlormercuribenzoic acid decreased the amount of reaction deposits at the level of all reactive sites and especially in mitochondria. The specificity of Mg2+ -ATPase demonstration in this paper is analysed taking into account several inherent shortcomings of the Wachstein-Meisel incubation medium and of the fixative. The different enzyme localizations, as well as their functional significances are discussed in relation with the findings of other authors."} {"id": "PMID:153701", "title": "Effect of intravenous calcium load on the serum calcium level in postmenopausal osteoporosis (a study of the pathogenesis, and diagnostic use of the test).", "content": "Analysis of calcium tolerance in suggested to represent a valuable diagnostic aid in osteoporosis, particulary in the menopause. The serum calcium level was found to exceed 11.0 mg/dl 60 min after the intravenous injection of 3.6 mg per kg body weight of Ca++ in all patients with osteoporosis, while the level was normal at that point of time in every subject without osteoporosis, including patients with bone disease other than osteoporosis. Administration of norandrosterone decanoate or dehydroepinandrosterone to patients with menopausal osteoporosis resulted in normalization of the post-load hypercalcaemia. Calcium tolerance of menopausal patients without osteoporosis was not affected by dehydroepiandrosterone.", "contents": "Effect of intravenous calcium load on the serum calcium level in postmenopausal osteoporosis (a study of the pathogenesis, and diagnostic use of the test). Analysis of calcium tolerance in suggested to represent a valuable diagnostic aid in osteoporosis, particulary in the menopause. The serum calcium level was found to exceed 11.0 mg/dl 60 min after the intravenous injection of 3.6 mg per kg body weight of Ca++ in all patients with osteoporosis, while the level was normal at that point of time in every subject without osteoporosis, including patients with bone disease other than osteoporosis. Administration of norandrosterone decanoate or dehydroepinandrosterone to patients with menopausal osteoporosis resulted in normalization of the post-load hypercalcaemia. Calcium tolerance of menopausal patients without osteoporosis was not affected by dehydroepiandrosterone."} {"id": "PMID:153702", "title": "Morphology and enzyme activities of the retinal capillaries in mice with the obese-hyperglycaemic syndrome (gene symbol ob).", "content": "The retinal capillary bed from 67 obese-hyperglycaemic mice and 64 lean litter mates was isolated by trypsin digestion and investigated with respect to structure and enzyme activities. There was no significant difference in the ratio between numbers of endothelial and mural cells. The capillary walls did not show any obvious structural differences and microaneurysms were not observed. The retinal vessels from the obese-hyperglycaemic mice, however, displayed significantly higher activities of the enzymes hydroxyacyl-CoA-dehydrogenase, asparate aminotransferase (ASAT) and adenylate kinase than their lean litter mates. The activities of glutathione reductase, glucose-6-phosphate dehydrogenase (G-6-PDH) and phosphofructokinase were similar in the two experimental groups. It is suggested that the present data reflect early metabolic disturbances related to diabetic retinopathy.", "contents": "Morphology and enzyme activities of the retinal capillaries in mice with the obese-hyperglycaemic syndrome (gene symbol ob). The retinal capillary bed from 67 obese-hyperglycaemic mice and 64 lean litter mates was isolated by trypsin digestion and investigated with respect to structure and enzyme activities. There was no significant difference in the ratio between numbers of endothelial and mural cells. The capillary walls did not show any obvious structural differences and microaneurysms were not observed. The retinal vessels from the obese-hyperglycaemic mice, however, displayed significantly higher activities of the enzymes hydroxyacyl-CoA-dehydrogenase, asparate aminotransferase (ASAT) and adenylate kinase than their lean litter mates. The activities of glutathione reductase, glucose-6-phosphate dehydrogenase (G-6-PDH) and phosphofructokinase were similar in the two experimental groups. It is suggested that the present data reflect early metabolic disturbances related to diabetic retinopathy."} {"id": "PMID:153703", "title": "Histiocytosis X. IV--Immunologic response assessed by lymphocyte transformation tests.", "content": "Eight children with histiocytosis X were investigated with reference to immunologic reactivity in vitro (PHA, PWM, Con-A and MLC testing). No significant impairment of immune function was detected, but a subnormal (statistically insignificant) response in the MLC test may suggest some abnormality of the T lymphocytes reacting against allogeneic cells. In a patient who relapsed a marked, but insignificant, increase in lymphocyte reactivity in vitro was observed.", "contents": "Histiocytosis X. IV--Immunologic response assessed by lymphocyte transformation tests. Eight children with histiocytosis X were investigated with reference to immunologic reactivity in vitro (PHA, PWM, Con-A and MLC testing). No significant impairment of immune function was detected, but a subnormal (statistically insignificant) response in the MLC test may suggest some abnormality of the T lymphocytes reacting against allogeneic cells. In a patient who relapsed a marked, but insignificant, increase in lymphocyte reactivity in vitro was observed."} {"id": "PMID:153706", "title": "Gray scale features of hematomas: an ultrasonic spectrum.", "content": "Forty-eight B-scan ultrasound examinations were performed on 25 patients with hematomas. Hematomas are usually spherical or ovoid within the abdomen, and lentiform within the pleural space or abdominal wall. They generally decrease in size with time, and usually have irregular walls. Hematomas contain a variable amount of internal echoes during the first month, and then gradually become anechoic. The sonographic appearance is not specific; an abscess may have a similar appearance. An old, anechoic hematoma may contain a gelatinous material which cannot be aspirated.", "contents": "Gray scale features of hematomas: an ultrasonic spectrum. Forty-eight B-scan ultrasound examinations were performed on 25 patients with hematomas. Hematomas are usually spherical or ovoid within the abdomen, and lentiform within the pleural space or abdominal wall. They generally decrease in size with time, and usually have irregular walls. Hematomas contain a variable amount of internal echoes during the first month, and then gradually become anechoic. The sonographic appearance is not specific; an abscess may have a similar appearance. An old, anechoic hematoma may contain a gelatinous material which cannot be aspirated."} {"id": "PMID:153707", "title": "Relationship of atrial fibrillatory wave amplitude to left atrial size and etiology of heart disease. An old generalization re-examined.", "content": "It is commonly stated that coarse f waves in atrial fibrillation suggest the presence of rheumatic heart disease and large left atrial size, whereas fine f waves indicate non-rheumatic disease and small left atrial size. Using echocardiography as a more reliable indicator of left atrial size, 37 consecutive patients with chronic atrial fibrillation were evaluated. The correlation coefficients between left atrial size and maximum f wave amplitude was -0.12 and -0.07, using average f wave amplitude. Only 53 per cent (9 of 17) of patients with rheumatic heart disease had f wave greater than 1 mm. and 56 per cent (10 of 18) of patients with f wave size less than or equal to 1 mm. had non-rheumatic disease. This study refutes the contention that the f wave amplitude in atrial fibrillation is correlated with either left atrial size or etiology of heart disease. It is possible that an intra-atrial conduction defect is responsible for coarse f wave morphology.", "contents": "Relationship of atrial fibrillatory wave amplitude to left atrial size and etiology of heart disease. An old generalization re-examined. It is commonly stated that coarse f waves in atrial fibrillation suggest the presence of rheumatic heart disease and large left atrial size, whereas fine f waves indicate non-rheumatic disease and small left atrial size. Using echocardiography as a more reliable indicator of left atrial size, 37 consecutive patients with chronic atrial fibrillation were evaluated. The correlation coefficients between left atrial size and maximum f wave amplitude was -0.12 and -0.07, using average f wave amplitude. Only 53 per cent (9 of 17) of patients with rheumatic heart disease had f wave greater than 1 mm. and 56 per cent (10 of 18) of patients with f wave size less than or equal to 1 mm. had non-rheumatic disease. This study refutes the contention that the f wave amplitude in atrial fibrillation is correlated with either left atrial size or etiology of heart disease. It is possible that an intra-atrial conduction defect is responsible for coarse f wave morphology."} {"id": "PMID:153713", "title": "Sampling the fetoplacental circulation. III. Combined laparoscopy-fetoscopy in the pregnant macaque for hemoglobin identification.", "content": "To demonstrate increased technical experience with fetoscopy and fetal blood sampling, two groups of macaques were compared to control animals. Group 2 had a perinatal mortality rate that was not significantly different from that of the control group. A 2.7 mm. Hopkins rod lens endoscope encased in an eccentric cannula, 3.8 mm. outside diameter, was used. When compared to the earlier test group (Group 1), the later test group (Group 2) showed greater adequacy of the fetal blood sample for laboratory analysis (P less than 0.01). Anthropometric and hematologic data collected at term births compared favorably in test and control groups, with the exception of the white blood cell count, which was significantly lower with fetoscopy (P less than 0.01). This is the first report of experimental fetoscopy with the use of a control group to provide precise data to aid in clarification of the ethical issues yet unresolved in this technology.", "contents": "Sampling the fetoplacental circulation. III. Combined laparoscopy-fetoscopy in the pregnant macaque for hemoglobin identification. To demonstrate increased technical experience with fetoscopy and fetal blood sampling, two groups of macaques were compared to control animals. Group 2 had a perinatal mortality rate that was not significantly different from that of the control group. A 2.7 mm. Hopkins rod lens endoscope encased in an eccentric cannula, 3.8 mm. outside diameter, was used. When compared to the earlier test group (Group 1), the later test group (Group 2) showed greater adequacy of the fetal blood sample for laboratory analysis (P less than 0.01). Anthropometric and hematologic data collected at term births compared favorably in test and control groups, with the exception of the white blood cell count, which was significantly lower with fetoscopy (P less than 0.01). This is the first report of experimental fetoscopy with the use of a control group to provide precise data to aid in clarification of the ethical issues yet unresolved in this technology."} {"id": "PMID:153714", "title": "Development of pulmonary arterial changes in rats fed Crotalaria spectabilis.", "content": "The early changes in pulmonary artery structure and the timing and development of right ventricular hypertrophy were examined in rats after ingestion of Crotalaria spectabilis; the arteries were distended with a Micropaque--gelatin mixture. The earliest change, detected at Day 3, is the appearance of new muscle in normally nonmuscular arteries. Increased medial wall thickness of the normally muscular arteries is apparent from Day 7, reaching significance in the smaller arteries from Day 10 and in the larger arteries from Day 14. A reduction in number of small, filled peripheral arteries is apparent at Day 14 and is significant at Day 21 as is the increase in the ratio of alveoli to arteries per unit area of section. Right ventricular hypertrophy is detected and significant at Day 21 and, like all the arterial changes, continues to increase to Day 35. Hypoxia produces similar changes to those described above, although without the inflammation seen after Crotalaria ingestion, but the time table is different. New muscle appears in both models at the same time, but the other changes appear more slowly after ingestion of Crotalaria spectabilis.", "contents": "Development of pulmonary arterial changes in rats fed Crotalaria spectabilis. The early changes in pulmonary artery structure and the timing and development of right ventricular hypertrophy were examined in rats after ingestion of Crotalaria spectabilis; the arteries were distended with a Micropaque--gelatin mixture. The earliest change, detected at Day 3, is the appearance of new muscle in normally nonmuscular arteries. Increased medial wall thickness of the normally muscular arteries is apparent from Day 7, reaching significance in the smaller arteries from Day 10 and in the larger arteries from Day 14. A reduction in number of small, filled peripheral arteries is apparent at Day 14 and is significant at Day 21 as is the increase in the ratio of alveoli to arteries per unit area of section. Right ventricular hypertrophy is detected and significant at Day 21 and, like all the arterial changes, continues to increase to Day 35. Hypoxia produces similar changes to those described above, although without the inflammation seen after Crotalaria ingestion, but the time table is different. New muscle appears in both models at the same time, but the other changes appear more slowly after ingestion of Crotalaria spectabilis."} {"id": "PMID:153712", "title": "Case report: mesangial IgA-IgG deposition in mixed cryoglobulinemia.", "content": "Glomerular deposits of immunoglobulin A (IgA) (and immunoglobulin G [IgG]) has been described in IgA-nephropathy (Berger's disease), in anaphylactoid purpura, and systemic lupus erythematosus. The pathogenesis of mesangial IgA deposits in these disease states is unclear. Circulating immune complexes have been speculated to be involved although their existence in blood in IgA nephropathies have never been reported. We describe a 53-year-old man who presented with a petechial rash in lower extremities accompanied by painful swelling of left ankle and wrist. Polyclonal elevation of IgA and IgG in serum was found, along with cryoglobulins containing IgA and IgG (rheumatoid factor positive). After two years, hematuria, mild proteinuria, and active urinary sediment developed and renal biopsy revealed focal proliferative changes. Immunofluorescence revealed predominantly mesangial deposits of IgA and IgG but no IgM nor complement. This experience suggests that circulating complexes consisting of IgA and IgG may lead to renal lesions presenting clinically and histologically in a way similar to that commonly seen in IgA nephropathies.", "contents": "Case report: mesangial IgA-IgG deposition in mixed cryoglobulinemia. Glomerular deposits of immunoglobulin A (IgA) (and immunoglobulin G [IgG]) has been described in IgA-nephropathy (Berger's disease), in anaphylactoid purpura, and systemic lupus erythematosus. The pathogenesis of mesangial IgA deposits in these disease states is unclear. Circulating immune complexes have been speculated to be involved although their existence in blood in IgA nephropathies have never been reported. We describe a 53-year-old man who presented with a petechial rash in lower extremities accompanied by painful swelling of left ankle and wrist. Polyclonal elevation of IgA and IgG in serum was found, along with cryoglobulins containing IgA and IgG (rheumatoid factor positive). After two years, hematuria, mild proteinuria, and active urinary sediment developed and renal biopsy revealed focal proliferative changes. Immunofluorescence revealed predominantly mesangial deposits of IgA and IgG but no IgM nor complement. This experience suggests that circulating complexes consisting of IgA and IgG may lead to renal lesions presenting clinically and histologically in a way similar to that commonly seen in IgA nephropathies."} {"id": "PMID:153716", "title": "The effect of EMG biofeedback on postoperative pain following abdominal surgery.", "content": "To investigate the effects of electromyography (EMG)-biofeedback on pain experienced during the immediate post-operative period following abdominal surgery, twelve patients were randomly assigned to either (1) EMG-biofeedback from abdominal muscles; (2) EMG-biofeedback from the frontalis muscles; or (3) were given no EMG treatment. EMG training consisted on one pre-operative 30 minute session, and three 30 minute postoperative sessions. All patients were able to reduce EMG activity. A within-sessions analysis of pain reports (on a 0-10 pain intensity scale) indicated that EMG biofeedback is an effective method of pain relief only when feedback is given to the muscle site involved in the operation.", "contents": "The effect of EMG biofeedback on postoperative pain following abdominal surgery. To investigate the effects of electromyography (EMG)-biofeedback on pain experienced during the immediate post-operative period following abdominal surgery, twelve patients were randomly assigned to either (1) EMG-biofeedback from abdominal muscles; (2) EMG-biofeedback from the frontalis muscles; or (3) were given no EMG treatment. EMG training consisted on one pre-operative 30 minute session, and three 30 minute postoperative sessions. All patients were able to reduce EMG activity. A within-sessions analysis of pain reports (on a 0-10 pain intensity scale) indicated that EMG biofeedback is an effective method of pain relief only when feedback is given to the muscle site involved in the operation."} {"id": "PMID:153717", "title": "Hypoxia with a third flowmeter tube on the anaesthetic machine.", "content": "Hypoxic mixtures of oxygen and nitrous oxide were demonstrated with three anaesthesia machines which had cyclopropane flowmeters. In one machine the bobbin did not prevent back flow and the hypoxic mixture occurred when the cyclopropane flow control was left open. Two other machines only delivered hypoxic mixtures if the cyclopropane bobbins were removed from their seats and the flow controls opened. The vaporizer on one machine increased the hypoxia when turned on.", "contents": "Hypoxia with a third flowmeter tube on the anaesthetic machine. Hypoxic mixtures of oxygen and nitrous oxide were demonstrated with three anaesthesia machines which had cyclopropane flowmeters. In one machine the bobbin did not prevent back flow and the hypoxic mixture occurred when the cyclopropane flow control was left open. Two other machines only delivered hypoxic mixtures if the cyclopropane bobbins were removed from their seats and the flow controls opened. The vaporizer on one machine increased the hypoxia when turned on."} {"id": "PMID:153720", "title": "Combination of Spigelian and Richter's hernias: a case report.", "content": "Spigelian and Richter's hernias, individually, are both moderately rare. To encounter a patient having both of these surgical diseases as a single entity is indeed unique. Such a patient with an acute partial enterocele of cecum (Richter's hernia) strangulated in a lateral ventral musculoaponeurotic defect (Spigelian hernia) was successfully treated with wedge cecectomy and simple herniorraphy.", "contents": "Combination of Spigelian and Richter's hernias: a case report. Spigelian and Richter's hernias, individually, are both moderately rare. To encounter a patient having both of these surgical diseases as a single entity is indeed unique. Such a patient with an acute partial enterocele of cecum (Richter's hernia) strangulated in a lateral ventral musculoaponeurotic defect (Spigelian hernia) was successfully treated with wedge cecectomy and simple herniorraphy."} {"id": "PMID:153721", "title": "[Dietary protein levels, and experimental inflammation in the rat].", "content": "The inflammatory response was studied using the contents (mucopolysaccharides and collagen of granuloma induced by turpentine in rats fed for 28 days after weaning), with semi-synthetic, isocaloric diets containing 0, 3.5, 9, 26 or 81% protein in the form of casein or with a laboratory chow. When the wet and dry weights and the water content of the granuloma are expressed in absolute values they show a substantial drop when the protein intake is low or excessive. If however the wet weight of the granuloma is expressed per 100 g of body weight, the differences become no longer significant, hence the importance of the nutritional state of the animal at the time of investigation. Using this test of the anti-inflammatory action of substances, it is necessary to differenciate between actual anti-inflammatory action and direct or secondary effects of the substance on the growth and behaviour of the animal. The levels of mucopolysaccharide drop in rats fed on hypo or hyper-proteinic diets, this would seem to be a sign of the decrease in the intensity of the anti-inflammatory response. What is more, the collagen itself undergoes modifications; there is a shift towards greater solubility of the fractions which would seem to indicate that a drop or a increase in the protein intake brings about a change in the processes of reticulation and maturation of the collagen; several hypothesis can be put forward to explain this phenomenon.", "contents": "[Dietary protein levels, and experimental inflammation in the rat]. The inflammatory response was studied using the contents (mucopolysaccharides and collagen of granuloma induced by turpentine in rats fed for 28 days after weaning), with semi-synthetic, isocaloric diets containing 0, 3.5, 9, 26 or 81% protein in the form of casein or with a laboratory chow. When the wet and dry weights and the water content of the granuloma are expressed in absolute values they show a substantial drop when the protein intake is low or excessive. If however the wet weight of the granuloma is expressed per 100 g of body weight, the differences become no longer significant, hence the importance of the nutritional state of the animal at the time of investigation. Using this test of the anti-inflammatory action of substances, it is necessary to differenciate between actual anti-inflammatory action and direct or secondary effects of the substance on the growth and behaviour of the animal. The levels of mucopolysaccharide drop in rats fed on hypo or hyper-proteinic diets, this would seem to be a sign of the decrease in the intensity of the anti-inflammatory response. What is more, the collagen itself undergoes modifications; there is a shift towards greater solubility of the fractions which would seem to indicate that a drop or a increase in the protein intake brings about a change in the processes of reticulation and maturation of the collagen; several hypothesis can be put forward to explain this phenomenon."} {"id": "PMID:153722", "title": "[Researches on the physiopathologic effects of rapeseed oil with high and low erucic acid content].", "content": "The physiopathological effects were studied of a common high erucic acid rapeseed oil as well as of Janpol, a low erucic acid oil produced of a rapeseed variety selected in Poland. Its erucic acid content equals 2.8% of total fatty acids. The studies were carried out on white male Wistar rats, 25 days old at the beginning of experiment. These animals were divided into 6 groups fed the diets in which 10 or 20% of kcal well supplied either by high erucic acid rapeseed oil, by Janpol rapeseed oil, or by the sunflower oil. The experiment lasted 6 months. Following parameters were determined: increase in body weight, the weight of selected organs, blood serum alkaline phosphatase and pseudocholinesterase activities, blood serum cholesterol and triglycerides level, the content of corticosterone in the adrenal glands and blood plasma. The liver was studied histochemically for the activity of acid and alkaline phosphatases and of ATP-ase, as well as for the presence of lipids. Morphological studies of the myocardium comprised macroscopic, histological and electron microscopic investigation. The low erucic acid rapeseed oil Janpol seems to evoke less disturbances than the high erucic acid one. Supplied in the amount corresponding to 10% of total calories intake the former exerts the effect on the biochemical and morphological parameters similar to that of sunflower oil. It can be thus assumed that the low erucic acid rapeseed oil Janpol can be used in the feeding of man when served in the amount lower than 10% of total calories.", "contents": "[Researches on the physiopathologic effects of rapeseed oil with high and low erucic acid content]. The physiopathological effects were studied of a common high erucic acid rapeseed oil as well as of Janpol, a low erucic acid oil produced of a rapeseed variety selected in Poland. Its erucic acid content equals 2.8% of total fatty acids. The studies were carried out on white male Wistar rats, 25 days old at the beginning of experiment. These animals were divided into 6 groups fed the diets in which 10 or 20% of kcal well supplied either by high erucic acid rapeseed oil, by Janpol rapeseed oil, or by the sunflower oil. The experiment lasted 6 months. Following parameters were determined: increase in body weight, the weight of selected organs, blood serum alkaline phosphatase and pseudocholinesterase activities, blood serum cholesterol and triglycerides level, the content of corticosterone in the adrenal glands and blood plasma. The liver was studied histochemically for the activity of acid and alkaline phosphatases and of ATP-ase, as well as for the presence of lipids. Morphological studies of the myocardium comprised macroscopic, histological and electron microscopic investigation. The low erucic acid rapeseed oil Janpol seems to evoke less disturbances than the high erucic acid one. Supplied in the amount corresponding to 10% of total calories intake the former exerts the effect on the biochemical and morphological parameters similar to that of sunflower oil. It can be thus assumed that the low erucic acid rapeseed oil Janpol can be used in the feeding of man when served in the amount lower than 10% of total calories."} {"id": "PMID:153726", "title": "Isolation and identification of the cytoplasmic membrane from Saccharomyces carlsbergensis by radioactive labeling.", "content": "The cytoplasmic membrane of Saccharomyces carlsbergensis was isolated by enzymatic digestion of the yeast cell wall, followed by lysis of the protoplasts and fractionation by ultracentrifugation in a discontinuous sucrose density gradient. Location of the cytoplasmic membrane fraction on the sucrose gradient was made by labeling intact protoplasts with [G-3H]dansyl chloride, and was settled at the 50% (wt/vol) sucrose gradient (d = 1.186 g/cm3). Approximately 80% of the radioactivity was found in the membrane fraction prepared in the presence of Mg2+ ions. However, when protease inhibitors were used in the preparation step, the membrane fraction contained over 90% of the total radioactivity. The presence of Mg2+ ions during membrane isolation and purification enhanced the aggregation of membrane components but, at higher concentrations, as well as in the prolonged presence of Mg2+ ions in the membrane suspension, it caused the breakdown of membrane components. The membrane preparation contained Mg2+-adenosine triphosphatase, which was insensitive to oligomycin and ouabain. The distribution of Mg2+-adenosine triphosphatase in different fractions during sucrose gradient is reported.", "contents": "Isolation and identification of the cytoplasmic membrane from Saccharomyces carlsbergensis by radioactive labeling. The cytoplasmic membrane of Saccharomyces carlsbergensis was isolated by enzymatic digestion of the yeast cell wall, followed by lysis of the protoplasts and fractionation by ultracentrifugation in a discontinuous sucrose density gradient. Location of the cytoplasmic membrane fraction on the sucrose gradient was made by labeling intact protoplasts with [G-3H]dansyl chloride, and was settled at the 50% (wt/vol) sucrose gradient (d = 1.186 g/cm3). Approximately 80% of the radioactivity was found in the membrane fraction prepared in the presence of Mg2+ ions. However, when protease inhibitors were used in the preparation step, the membrane fraction contained over 90% of the total radioactivity. The presence of Mg2+ ions during membrane isolation and purification enhanced the aggregation of membrane components but, at higher concentrations, as well as in the prolonged presence of Mg2+ ions in the membrane suspension, it caused the breakdown of membrane components. The membrane preparation contained Mg2+-adenosine triphosphatase, which was insensitive to oligomycin and ouabain. The distribution of Mg2+-adenosine triphosphatase in different fractions during sucrose gradient is reported."} {"id": "PMID:153723", "title": "[Alopecia areata and trisomy 21. About 2 cases (author's transl)].", "content": "Two cases of alopecia areata coexisting with trisomy 21 are reported. In the first case, the two diseases were associated with Hashimoto's thyroiditis and in the second, with vitiligo. Pathogenic implications are discussed.", "contents": "[Alopecia areata and trisomy 21. About 2 cases (author's transl)]. Two cases of alopecia areata coexisting with trisomy 21 are reported. In the first case, the two diseases were associated with Hashimoto's thyroiditis and in the second, with vitiligo. Pathogenic implications are discussed."} {"id": "PMID:153724", "title": "[Malignant atrophying papulosis (Degos' disease) (author's transl)].", "content": "From 74 observations, 55 p. 100 of which caused death by intestinal lesions, the author searches, through the symptomatology of the disease, for possible factors of prognosis. No relation between the importance of cutaneous symptoms and the appearance of intestinal symptoms has been found. There is no constancy in the chronological evolution of the lesions. The interest of laparoscopy is emphasized. No biological constant seems specific of the disease. A few modest arguments are suggestive of an auto-immune disease. In spite of a varied range of therapeutic orientations, none of them could prove to be efficient, not even heparinotherapy.", "contents": "[Malignant atrophying papulosis (Degos' disease) (author's transl)]. From 74 observations, 55 p. 100 of which caused death by intestinal lesions, the author searches, through the symptomatology of the disease, for possible factors of prognosis. No relation between the importance of cutaneous symptoms and the appearance of intestinal symptoms has been found. There is no constancy in the chronological evolution of the lesions. The interest of laparoscopy is emphasized. No biological constant seems specific of the disease. A few modest arguments are suggestive of an auto-immune disease. In spite of a varied range of therapeutic orientations, none of them could prove to be efficient, not even heparinotherapy."} {"id": "PMID:153729", "title": "Iodochlorhydroxyquin-hydrocortisone treatment of fungal infections. Double-blind trial.", "content": "A double-blind multicenter study compared the antifungal effectiveness of an iodochlorhydroxyquin-hydrocoritsone cream with that of its individual components in 354 patients with cutaneous fungal infections. After seven days of treatment, the combination was considerably better than hydrocortisone or the cream vehicle with respect to erythema, scaling, itching, and patients' and physicians' evaluations. The proportion of patients in the iodochlorhydroxyquin-hydrocortisone and iodochlorhydroxyquin groups who changed from positive results on potassium hydroxide examination at baseline to negative results on potassium hydroxide examination after treatment was significantly greater than that in the hydrocortisone and placebo groups. The conversion rate associated with the iodochlorhydroxyquin-hydrocortisone and the iodochlorhydroxyquin treatments was significantly different from that associated with hydrocortisone alone or placebo treatment.", "contents": "Iodochlorhydroxyquin-hydrocortisone treatment of fungal infections. Double-blind trial. A double-blind multicenter study compared the antifungal effectiveness of an iodochlorhydroxyquin-hydrocoritsone cream with that of its individual components in 354 patients with cutaneous fungal infections. After seven days of treatment, the combination was considerably better than hydrocortisone or the cream vehicle with respect to erythema, scaling, itching, and patients' and physicians' evaluations. The proportion of patients in the iodochlorhydroxyquin-hydrocortisone and iodochlorhydroxyquin groups who changed from positive results on potassium hydroxide examination at baseline to negative results on potassium hydroxide examination after treatment was significantly greater than that in the hydrocortisone and placebo groups. The conversion rate associated with the iodochlorhydroxyquin-hydrocortisone and the iodochlorhydroxyquin treatments was significantly different from that associated with hydrocortisone alone or placebo treatment."} {"id": "PMID:153730", "title": "Zinc sulfate in acne vulgaris.", "content": "The effects of orally administered zinc sulfate in 52 patients with mild to moderate acne vulgaris were compared to those of a placebo capsule. The numbers of comedones, papules, pustules, infiltrates, and cysts were counted at each visit over a 12-week period. Forty patients completed the study. Zinc appeared to have a somewhat beneficial effect on pustules but not on comedones, papules, infiltrates, or cysts. Fourteen patients (50%) in the zinc group had side effects of nausea, vomiting, or diarrhea. Six patients (21%) in the zinc group could not tolerate the nausea and withdrew from the study.", "contents": "Zinc sulfate in acne vulgaris. The effects of orally administered zinc sulfate in 52 patients with mild to moderate acne vulgaris were compared to those of a placebo capsule. The numbers of comedones, papules, pustules, infiltrates, and cysts were counted at each visit over a 12-week period. Forty patients completed the study. Zinc appeared to have a somewhat beneficial effect on pustules but not on comedones, papules, infiltrates, or cysts. Fourteen patients (50%) in the zinc group had side effects of nausea, vomiting, or diarrhea. Six patients (21%) in the zinc group could not tolerate the nausea and withdrew from the study."} {"id": "PMID:153731", "title": "Florid cutaneous papillomatosis.", "content": "The abrupt onset of acanthosis nigricans (AN) or of multiple seborrheic keratoses in middle-aged or older people is often associated with underlying malignant neoplasms. We describe a 64-year-old woman who developed a large number of verrucous papillomas on the trunk and extremities, followed within a few months by the sudden appearance of both the lesions of AN and those of multiple seborrheic keratoses. Laparotomy disclosed a gastric adenocarcinoma. A number of similar cases have been described in the literature. It is emphasized that patients with suddenly appearing verrucous papillomas should be examined carefully for an underlying cancer. To call attention to this eruption, which may be mistaken for generalized warts, we suggest the term \"florid cutaneous papillomatosis\".", "contents": "Florid cutaneous papillomatosis. The abrupt onset of acanthosis nigricans (AN) or of multiple seborrheic keratoses in middle-aged or older people is often associated with underlying malignant neoplasms. We describe a 64-year-old woman who developed a large number of verrucous papillomas on the trunk and extremities, followed within a few months by the sudden appearance of both the lesions of AN and those of multiple seborrheic keratoses. Laparotomy disclosed a gastric adenocarcinoma. A number of similar cases have been described in the literature. It is emphasized that patients with suddenly appearing verrucous papillomas should be examined carefully for an underlying cancer. To call attention to this eruption, which may be mistaken for generalized warts, we suggest the term \"florid cutaneous papillomatosis\"."} {"id": "PMID:153732", "title": "Familial comedones. Evidence for autosomal dominant inheritance.", "content": "Thirteen members of a family had multiple comedones. Three other relatives were also ascertained to be affected. This peculiar dermatosis affected both sexes and was present in one individual as young as 10 years of age. The lesions were more numerous in male family members, increasing in number with age. The pedigree showed a definite pattern of autosomal dominant inheritance.", "contents": "Familial comedones. Evidence for autosomal dominant inheritance. Thirteen members of a family had multiple comedones. Three other relatives were also ascertained to be affected. This peculiar dermatosis affected both sexes and was present in one individual as young as 10 years of age. The lesions were more numerous in male family members, increasing in number with age. The pedigree showed a definite pattern of autosomal dominant inheritance."} {"id": "PMID:153733", "title": "Urticarial vasculitis: report of a case and review of the literature.", "content": "A woman with cutaneous vasculitis had a severe bullous eruption that was suggestive of erythema multiforme. The patient also had a history of recurrent urticaria that continued intermittently for over a year of follow-up examination. Skin biopsy specimens of both urticarial and erythema and multiforme lesions showed leukocytoclastic vasculitis. An illness resembling systemic lupus erythematosus (SLE) is suggested by transient, low-titer, positive antinuclear antibody tests, persistent deposits of immunoglobulin and complement in normal skin, arthralgias, circulating immune complexes, and chronic hypocomplementemia. This case is similar to cases previously reported as \"hypocomplementemic vasculitis,\" an \"unusual SLE-related syndrome,\" and \"urticaria with vasculitis.\"", "contents": "Urticarial vasculitis: report of a case and review of the literature. A woman with cutaneous vasculitis had a severe bullous eruption that was suggestive of erythema multiforme. The patient also had a history of recurrent urticaria that continued intermittently for over a year of follow-up examination. Skin biopsy specimens of both urticarial and erythema and multiforme lesions showed leukocytoclastic vasculitis. An illness resembling systemic lupus erythematosus (SLE) is suggested by transient, low-titer, positive antinuclear antibody tests, persistent deposits of immunoglobulin and complement in normal skin, arthralgias, circulating immune complexes, and chronic hypocomplementemia. This case is similar to cases previously reported as \"hypocomplementemic vasculitis,\" an \"unusual SLE-related syndrome,\" and \"urticaria with vasculitis.\""} {"id": "PMID:153734", "title": "Autogenous profundaplasty: The key to long-term patency in secondary repair of aortofemoral graft occlusion.", "content": "The records of 281 patients undergoing aortic grafting to 522 femoral arteries over a period of 18 years were reviewed. Fifty-four patients suffering graft limb occlusion to 71 femoral arteries requiring subsequent secondary repair were identified for detailed analysis. Occlusive disease of the profunda femoris artery was identified as the primary cause of thrombosis. Repair consisted of profunda femoris angioplasty, and transfemoral retrograde graft thrombectomy was possible in all but three instances which were managed by cross-over femoral-femoral bypass. In no instance was laparotomy and abdominal graft replacement necessary. The 30 day operative survival and graft patency were 100%. Analysis of factors that have influenced late graft patency demonstrated that the key factors were the method of profundaplasty and the association of diabetes mellitus. When autogenous profundaplasty (on-lay arterial patches, saphenous vein, or limited endarterectomy) was employed, the overall patency combining diabetics and non-diabetics was two and one-half times greater than when profundaplasty was performed with an on-lay Dacron((R)) patch. If diabetics were separated from nondiabetics in the autogenous angioplasty group, the 36 month patency for non-diabetics was 85%, and 0% for diabetics. We conclude that autogenous profundaplasty provides considerable advantage from the standpoint of long-term patency and that the diabetic patients are relatively poor candidates for secondary arterial repair of an occluded aortofemoral bypass graft.", "contents": "Autogenous profundaplasty: The key to long-term patency in secondary repair of aortofemoral graft occlusion. The records of 281 patients undergoing aortic grafting to 522 femoral arteries over a period of 18 years were reviewed. Fifty-four patients suffering graft limb occlusion to 71 femoral arteries requiring subsequent secondary repair were identified for detailed analysis. Occlusive disease of the profunda femoris artery was identified as the primary cause of thrombosis. Repair consisted of profunda femoris angioplasty, and transfemoral retrograde graft thrombectomy was possible in all but three instances which were managed by cross-over femoral-femoral bypass. In no instance was laparotomy and abdominal graft replacement necessary. The 30 day operative survival and graft patency were 100%. Analysis of factors that have influenced late graft patency demonstrated that the key factors were the method of profundaplasty and the association of diabetes mellitus. When autogenous profundaplasty (on-lay arterial patches, saphenous vein, or limited endarterectomy) was employed, the overall patency combining diabetics and non-diabetics was two and one-half times greater than when profundaplasty was performed with an on-lay Dacron((R)) patch. If diabetics were separated from nondiabetics in the autogenous angioplasty group, the 36 month patency for non-diabetics was 85%, and 0% for diabetics. We conclude that autogenous profundaplasty provides considerable advantage from the standpoint of long-term patency and that the diabetic patients are relatively poor candidates for secondary arterial repair of an occluded aortofemoral bypass graft."} {"id": "PMID:153735", "title": "6-Chloro-2(1-piperazinyl) quinoxaline (CPQ): action on serotonin-induced behavioral responses and interactions with chloromethamphetamine and dimethyl-meta-tyramine.", "content": "6-Chloro-2(1-piperazinyl) quinoxaline (CPQ) was examined pharmacologically and biochemically as an inhibitor of the neuronal reuptake of serotonin, dopamine and norepinephrine. The compound was 25-50 times more potent than chlorimipramine in potentiating the head-twitch response to 5-hydroxytryptophan (5-HTP) and in antagonizing p-chloromethamphetamine (PCMA)-induced depletion of brain serotonin in rats. CPQ also potentiated the forepaw clonus produced by 5HTP in rats and antagonized PCMA-induced head twitches. At dose levels 30 times those necessary to significantly affect serotoninergic systems, CPQ was ineffective in antagonizing either tetrabenazine-induced sedation in mice or the depletion of rat brain and heart norepinephrine or brain dopamine produced by 4, alpha-dimethylmeta-tyramine (H77/77). The data indicate that CPQ exhibits a high degree of potency and selectivity in inhibiting the neuronal reuptake of serotonin.", "contents": "6-Chloro-2(1-piperazinyl) quinoxaline (CPQ): action on serotonin-induced behavioral responses and interactions with chloromethamphetamine and dimethyl-meta-tyramine. 6-Chloro-2(1-piperazinyl) quinoxaline (CPQ) was examined pharmacologically and biochemically as an inhibitor of the neuronal reuptake of serotonin, dopamine and norepinephrine. The compound was 25-50 times more potent than chlorimipramine in potentiating the head-twitch response to 5-hydroxytryptophan (5-HTP) and in antagonizing p-chloromethamphetamine (PCMA)-induced depletion of brain serotonin in rats. CPQ also potentiated the forepaw clonus produced by 5HTP in rats and antagonized PCMA-induced head twitches. At dose levels 30 times those necessary to significantly affect serotoninergic systems, CPQ was ineffective in antagonizing either tetrabenazine-induced sedation in mice or the depletion of rat brain and heart norepinephrine or brain dopamine produced by 4, alpha-dimethylmeta-tyramine (H77/77). The data indicate that CPQ exhibits a high degree of potency and selectivity in inhibiting the neuronal reuptake of serotonin."} {"id": "PMID:153736", "title": "Possible mechanisms of sustained tremor induction by nicotine in pilocarpine treated animals.", "content": "Alterations of steady state and metabolism of putative neurotransmitters were studied in the brain of rats with a sustained tremor evoked by nicotine and pilocarpine. The norepinephrine content in several brain regions was decreased whereas striatal dopamine was unchanged. Homovanillic acid concentrations were slightly increased, while 5-hydroxyindoleacetic acid concentrations were markedly increased. Pilocarpine alone increased the 5-hydroxytryptamine (5-HT) turnover rate at high ambient temperature (30-32 degrees C), but not at normal ambient temperature (22 +/- 2 degrees C), atropine partially blocked the increase of 5-HT turnover rate by pilocarpine. Pretreatment with p-chlorophenylalanine and hemicholinium-3 decreased the tremor intensity elicited by nicotine and pilocarpine . It is proposed that the increase of cholinergic function caused by nicotine and the activation of muscarinic receptors and the increase in 5-HT function caused by pilocarpine might be involved in the mechanisms of tremor induction by nicotine and pilocarpine.", "contents": "Possible mechanisms of sustained tremor induction by nicotine in pilocarpine treated animals. Alterations of steady state and metabolism of putative neurotransmitters were studied in the brain of rats with a sustained tremor evoked by nicotine and pilocarpine. The norepinephrine content in several brain regions was decreased whereas striatal dopamine was unchanged. Homovanillic acid concentrations were slightly increased, while 5-hydroxyindoleacetic acid concentrations were markedly increased. Pilocarpine alone increased the 5-hydroxytryptamine (5-HT) turnover rate at high ambient temperature (30-32 degrees C), but not at normal ambient temperature (22 +/- 2 degrees C), atropine partially blocked the increase of 5-HT turnover rate by pilocarpine. Pretreatment with p-chlorophenylalanine and hemicholinium-3 decreased the tremor intensity elicited by nicotine and pilocarpine . It is proposed that the increase of cholinergic function caused by nicotine and the activation of muscarinic receptors and the increase in 5-HT function caused by pilocarpine might be involved in the mechanisms of tremor induction by nicotine and pilocarpine."} {"id": "PMID:153737", "title": "Differential deoxyribonucleic acid synthesis during microcycle conidiation in Neurospora crassa.", "content": "In conidia of Neurospora crassa germinating at 25 degrees C, DNA synthesis measured by incorporation of tritiated adenosine reaches a maximum soon after the outgrowth of the germ tube (6--7 h after inoculation). In conidia heat-treated at 46 degrees C (for 15 h), a maximum of incorporation of the DNA precursor occurs already 1 h after inoculation, then the incorporation progressively declines until the end of the heat-shock. When such conidia are shifted to 25 degrees C, a maximum of DNA synthesis occurs during the development of the presumptive conidiophore as at the outgrowth of normal germ tubes. This wave of DNA synthesis is followed by a second maximum of DNA synthesis, occurring only in the microcyclized cultures, when the premature differentiation of proconidia takes place. Prevention of this second wave of DNA synthesis with hydroxyurea or 5-fluorodeoxyuridine respectively reduces or fully inhibits such induced conidial differentiation.", "contents": "Differential deoxyribonucleic acid synthesis during microcycle conidiation in Neurospora crassa. In conidia of Neurospora crassa germinating at 25 degrees C, DNA synthesis measured by incorporation of tritiated adenosine reaches a maximum soon after the outgrowth of the germ tube (6--7 h after inoculation). In conidia heat-treated at 46 degrees C (for 15 h), a maximum of incorporation of the DNA precursor occurs already 1 h after inoculation, then the incorporation progressively declines until the end of the heat-shock. When such conidia are shifted to 25 degrees C, a maximum of DNA synthesis occurs during the development of the presumptive conidiophore as at the outgrowth of normal germ tubes. This wave of DNA synthesis is followed by a second maximum of DNA synthesis, occurring only in the microcyclized cultures, when the premature differentiation of proconidia takes place. Prevention of this second wave of DNA synthesis with hydroxyurea or 5-fluorodeoxyuridine respectively reduces or fully inhibits such induced conidial differentiation."} {"id": "PMID:153738", "title": "Stress management training for the handicapped.", "content": "Stress Management Training (SMT) is described for teaching handicapped patients the use of relaxation as a coping skill. The procedure combines progressive muscle relaxation and clinical meditation into a standardized but flexible 8-session protocol. The training consists of 3 components: First, the patient is given a cognitive understanding of stress and relaxation. Second, the patient is taught to relax by controlling muscle tension and sympathetic activation. Third, the patient adapts the relaxation skill to real-life stress situations. Case reports demonstrating the process are included. Methods of assessing outcome and adaptations for particular handicaps are described.", "contents": "Stress management training for the handicapped. Stress Management Training (SMT) is described for teaching handicapped patients the use of relaxation as a coping skill. The procedure combines progressive muscle relaxation and clinical meditation into a standardized but flexible 8-session protocol. The training consists of 3 components: First, the patient is given a cognitive understanding of stress and relaxation. Second, the patient is taught to relax by controlling muscle tension and sympathetic activation. Third, the patient adapts the relaxation skill to real-life stress situations. Case reports demonstrating the process are included. Methods of assessing outcome and adaptations for particular handicaps are described."} {"id": "PMID:153740", "title": "[Histochemical data on changes of various indicators of protein metabolism in the myocardium beyond the infarct zone].", "content": "Changes in some values of protein metabolism in the heart muscle (the activity of myosin ATPase, leucilaminopeptidase, glutamate dehydrogenase, as well as the content of SH-groups, urea, RNA and DNA) were studied by histochemical methods in the parts of the myocardium remote from the zone of the ligated coronary artery. Disorders in the metabolism of nucleic acids were found to consist in nuclear polymorphism and in the development of regressive changes in some nuclei down to necrobiosis as well as in a decrease of the RNA content within the first 12 hours after ligation of the coronary artery. Subsequently, the amount of RNA increased. An increase in the amount of SH-groups, in the activity of leucilaminopeptidase and a decrease in the amount of glutamate dehydrogenase, formation of crystals of xanthhydrolurea as well as in increase in the activity of myosin ATP-ase early in the experiment attest to the occurrence of heterogeneous disorders of protein metabolism in parts of the myocardium beyond the infarction zone.", "contents": "[Histochemical data on changes of various indicators of protein metabolism in the myocardium beyond the infarct zone]. Changes in some values of protein metabolism in the heart muscle (the activity of myosin ATPase, leucilaminopeptidase, glutamate dehydrogenase, as well as the content of SH-groups, urea, RNA and DNA) were studied by histochemical methods in the parts of the myocardium remote from the zone of the ligated coronary artery. Disorders in the metabolism of nucleic acids were found to consist in nuclear polymorphism and in the development of regressive changes in some nuclei down to necrobiosis as well as in a decrease of the RNA content within the first 12 hours after ligation of the coronary artery. Subsequently, the amount of RNA increased. An increase in the amount of SH-groups, in the activity of leucilaminopeptidase and a decrease in the amount of glutamate dehydrogenase, formation of crystals of xanthhydrolurea as well as in increase in the activity of myosin ATP-ase early in the experiment attest to the occurrence of heterogeneous disorders of protein metabolism in parts of the myocardium beyond the infarction zone."} {"id": "PMID:153741", "title": "[Mechanisms of carcinogenesis associated with DNA repair].", "content": "The paper presents data from the literature and the author's own materials on the correlation between the extent of activity of reparation processes and the development of cell malignization. A review cites the results of investigations on the molecular mechanisms in some hereditary human diseases in which a defect in some stages of the reparation processes has been found (xeroderma, ataxia telangesthesia. Fanconi anemia, Down's syndrome, etc.). These diseases are also characterized by a high rate of neoplasia development. It is emphasized that inhibition of the reparation process is observed only in the first stages of normal cell transformation into a malignant one. A correlation between carcinogenic and mutagenic activity of chemical compounds which is in favour of the mutation hypothesis of the origin of tumours is discussed.", "contents": "[Mechanisms of carcinogenesis associated with DNA repair]. The paper presents data from the literature and the author's own materials on the correlation between the extent of activity of reparation processes and the development of cell malignization. A review cites the results of investigations on the molecular mechanisms in some hereditary human diseases in which a defect in some stages of the reparation processes has been found (xeroderma, ataxia telangesthesia. Fanconi anemia, Down's syndrome, etc.). These diseases are also characterized by a high rate of neoplasia development. It is emphasized that inhibition of the reparation process is observed only in the first stages of normal cell transformation into a malignant one. A correlation between carcinogenic and mutagenic activity of chemical compounds which is in favour of the mutation hypothesis of the origin of tumours is discussed."} {"id": "PMID:153743", "title": "Orthopaedic pitfalls.", "content": "When presented with an orthopaedic problem, rational management cannot occur without a reasonable diagnosis. Such a diagnosis can only be made by listening to the patient's history, and by examining him with a clear knowledge of important and relevant anatomy. Such relevant anatomy has been outlined in order to make sense of the symptom complexes in: --arm pain --knee pain --back pain without sciatica --back pain with sciatica The behaviour of collagen, which takes three weeks to heal and at least three weeks more to strengthen, is the basis of rational treatment of ligamentous injuries. Advice is given on specific situations to avoid the pitfalls of treatment which is too much, too little, too late or too soon.", "contents": "Orthopaedic pitfalls. When presented with an orthopaedic problem, rational management cannot occur without a reasonable diagnosis. Such a diagnosis can only be made by listening to the patient's history, and by examining him with a clear knowledge of important and relevant anatomy. Such relevant anatomy has been outlined in order to make sense of the symptom complexes in: --arm pain --knee pain --back pain without sciatica --back pain with sciatica The behaviour of collagen, which takes three weeks to heal and at least three weeks more to strengthen, is the basis of rational treatment of ligamentous injuries. Advice is given on specific situations to avoid the pitfalls of treatment which is too much, too little, too late or too soon."} {"id": "PMID:153745", "title": "Isolation and properties of brain alpha-actinin.", "content": "alpha-Actinin isolated from bovine brain migrated on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis like muscle alpha-actinin with an apparent mol.wt. of 100000 and cross-reacted with antibodies to muscle alpha-actinin. Brain alpha-actinin modulated actin-myosin Mg2+-activated adenosine triphosphatase activity and, when bound by polystyrene particles, was found to bind muscle actin and tropomyosin from solution. Brain alpha-actinin, in conjunction with the other components of the contractile and relaxing complex, may play a role in the release of neurotransmitters from synaptic vesicles.", "contents": "Isolation and properties of brain alpha-actinin. alpha-Actinin isolated from bovine brain migrated on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis like muscle alpha-actinin with an apparent mol.wt. of 100000 and cross-reacted with antibodies to muscle alpha-actinin. Brain alpha-actinin modulated actin-myosin Mg2+-activated adenosine triphosphatase activity and, when bound by polystyrene particles, was found to bind muscle actin and tropomyosin from solution. Brain alpha-actinin, in conjunction with the other components of the contractile and relaxing complex, may play a role in the release of neurotransmitters from synaptic vesicles."} {"id": "PMID:153749", "title": "Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells.", "content": "T cell suppressor function in patients with systemic lupus erythematosus (SLE) was evaluated by studying the ability of concanavalin A- (Con A) activated T cells to suppress proliferative responses by responder cells autologous with the Con A-activated T cells. Impaired suppressor T-cell activity in patients with SLE was observed with regard to three effector functions: 1) the allogeneic response of T cells, 2) the Con A response of T cells, and 3) the B cell response to pokeweed mitogen (PWM). No defect was found with regard to suppression of the T-cell response to phytohemagglutinin (PHA). Mixing experiments between SLE and normal cells were carried out to further define the nature of the SLE suppressor defect. When responder cells from SLE patients were cultured with Con A-activated T cells from normal controls, the normal suppressor T cells caused suppression of SLE responder cells. In contrast, Con A-activated T cells from SLE patients were incapable of exerting suppressor effects on normal responder cells. These observations indicate that the impaired suppressor activity in SLE patients resides in the generation of suppressor T cells, rather than in the response to suppressor T cell signals.", "contents": "Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells. T cell suppressor function in patients with systemic lupus erythematosus (SLE) was evaluated by studying the ability of concanavalin A- (Con A) activated T cells to suppress proliferative responses by responder cells autologous with the Con A-activated T cells. Impaired suppressor T-cell activity in patients with SLE was observed with regard to three effector functions: 1) the allogeneic response of T cells, 2) the Con A response of T cells, and 3) the B cell response to pokeweed mitogen (PWM). No defect was found with regard to suppression of the T-cell response to phytohemagglutinin (PHA). Mixing experiments between SLE and normal cells were carried out to further define the nature of the SLE suppressor defect. When responder cells from SLE patients were cultured with Con A-activated T cells from normal controls, the normal suppressor T cells caused suppression of SLE responder cells. In contrast, Con A-activated T cells from SLE patients were incapable of exerting suppressor effects on normal responder cells. These observations indicate that the impaired suppressor activity in SLE patients resides in the generation of suppressor T cells, rather than in the response to suppressor T cell signals."} {"id": "PMID:153750", "title": "Mixed lymphocyte reaction in healthy women with rheumatoid factor. Lack of association with HLA-Dw4.", "content": "In independent studies, 51% and 36% of patients with rheumatoid arthritis have been shown to possess HLA-Dw4 compared to 7% and 13% of controls. In one study Dw4 positive patients more frequently had rheumatoid factor in their sera than did Dw4 negative patients. In order to determine if the Dw4 specificity is associated with the disease or with the presence of rheumatoid factor, the frequency of this HLA antigen has been determined in 24 healthy women known to have rheumatoid factor (median titer 1:160). Only 3 were found to have the Dw4 specificity, suggesting that this specificity is not associated with rheumatoid factor in the absence of rheumatoid arthritis.", "contents": "Mixed lymphocyte reaction in healthy women with rheumatoid factor. Lack of association with HLA-Dw4. In independent studies, 51% and 36% of patients with rheumatoid arthritis have been shown to possess HLA-Dw4 compared to 7% and 13% of controls. In one study Dw4 positive patients more frequently had rheumatoid factor in their sera than did Dw4 negative patients. In order to determine if the Dw4 specificity is associated with the disease or with the presence of rheumatoid factor, the frequency of this HLA antigen has been determined in 24 healthy women known to have rheumatoid factor (median titer 1:160). Only 3 were found to have the Dw4 specificity, suggesting that this specificity is not associated with rheumatoid factor in the absence of rheumatoid arthritis."} {"id": "PMID:153764", "title": "Testosterone production with hydatidiform moles--in vitro and in vivo studies.", "content": "Fresh molar tissues obtained from seven patients were incubated in vitro with dehydroepiandrosterone and androstenedione. The testosterone concentration in molar tissue ranged from 5.4 ng/g wet weight to 43.8 ng/g wet weight. Both precursors were readily converted to testosterone indicating that 17-hydroxysteroid dehydrogenase and 3beta-hydroxysteroid dehydrogenase are present in molar trophoblast. A 50 mg dose of dehydroepiandrosterone was infused into patients with hydatidiform mole before and after uterine evacuation. There was a testosterone peak preceding an oestrogen rise which disappeared after uterine evacuation. It is suggested that the elevated testosterone level in molar pregnancy is mainly due to the conversion of dehydroepiandrosterone in the molar trophoblast.", "contents": "Testosterone production with hydatidiform moles--in vitro and in vivo studies. Fresh molar tissues obtained from seven patients were incubated in vitro with dehydroepiandrosterone and androstenedione. The testosterone concentration in molar tissue ranged from 5.4 ng/g wet weight to 43.8 ng/g wet weight. Both precursors were readily converted to testosterone indicating that 17-hydroxysteroid dehydrogenase and 3beta-hydroxysteroid dehydrogenase are present in molar trophoblast. A 50 mg dose of dehydroepiandrosterone was infused into patients with hydatidiform mole before and after uterine evacuation. There was a testosterone peak preceding an oestrogen rise which disappeared after uterine evacuation. It is suggested that the elevated testosterone level in molar pregnancy is mainly due to the conversion of dehydroepiandrosterone in the molar trophoblast."} {"id": "PMID:153765", "title": "Ionic charge on phospholipids and their interaction with the mitochondrial adenosine triphosphatase.", "content": "The activity of the lipid-depleted, oligomycin-sensitive mitochondrial ATPase has been measured in the presence of liposomes prepared from mixtures of phosphatidylglycerol and phosphatidylglycerol lysine. Enzyme activity increased linearly with an increase in the negative charge of liposomes prepared from the phosphatidylglycerol-phosphatidylglycerol lysine mixtures. The electrophoretic mobility and activating capacity of liposomes of several other phospholipids were determined. A linear relationship between electrophoretic mobility of the liposomes and oligomycin-sensitive activity was again apparent. These observations demonstrate that the activity of the ATPase is directly proportional to the ionic charge on phospholipid activators if the acyl chain composition of the phosphoglycerides is relatively constant.", "contents": "Ionic charge on phospholipids and their interaction with the mitochondrial adenosine triphosphatase. The activity of the lipid-depleted, oligomycin-sensitive mitochondrial ATPase has been measured in the presence of liposomes prepared from mixtures of phosphatidylglycerol and phosphatidylglycerol lysine. Enzyme activity increased linearly with an increase in the negative charge of liposomes prepared from the phosphatidylglycerol-phosphatidylglycerol lysine mixtures. The electrophoretic mobility and activating capacity of liposomes of several other phospholipids were determined. A linear relationship between electrophoretic mobility of the liposomes and oligomycin-sensitive activity was again apparent. These observations demonstrate that the activity of the ATPase is directly proportional to the ionic charge on phospholipid activators if the acyl chain composition of the phosphoglycerides is relatively constant."} {"id": "PMID:153766", "title": "Modification of high molecular weight plasmic degradation products of human crosslinked fibrin.", "content": "The predominant high molecular weight products of plasmic digestion of human crosslinked fibrin Fragments DD, E and (DD)E complex were purified by column gel filtration in a non-dissociating buffer or by ion-exchange chromatography on DEAE-cellulose. The structure of the degradation products was studied by proteolytic degradation, polyacrylamide gel electrophoresis immunodiffusion and sucrose density gradient centrifugation. Unaltered derivatives were very resistant to proteolytic degradation by plasmin. In the the presence of 10 mM EDTA the (DD)E complex did not dissociate, but similar to Fragment DD, became susceptible to plasmic degradation forming Fragment D derivatives. The (DD)E complex dissociated in 3 M urea at pH 5.5, had an altered conformation as evidenced by its aggregability and by its increased susceptibility to degradation by plasmin resulting in the formation of Fragment d. The gammagamma chain remnants of Fragment DD were attacked first, followed by cleavage of the beta chain remnants. It is concluded that plasmin resistance is a function of the intact structure and it is not directly dependent on the presence of the crosslink bonds or calcium ions.", "contents": "Modification of high molecular weight plasmic degradation products of human crosslinked fibrin. The predominant high molecular weight products of plasmic digestion of human crosslinked fibrin Fragments DD, E and (DD)E complex were purified by column gel filtration in a non-dissociating buffer or by ion-exchange chromatography on DEAE-cellulose. The structure of the degradation products was studied by proteolytic degradation, polyacrylamide gel electrophoresis immunodiffusion and sucrose density gradient centrifugation. Unaltered derivatives were very resistant to proteolytic degradation by plasmin. In the the presence of 10 mM EDTA the (DD)E complex did not dissociate, but similar to Fragment DD, became susceptible to plasmic degradation forming Fragment D derivatives. The (DD)E complex dissociated in 3 M urea at pH 5.5, had an altered conformation as evidenced by its aggregability and by its increased susceptibility to degradation by plasmin resulting in the formation of Fragment d. The gammagamma chain remnants of Fragment DD were attacked first, followed by cleavage of the beta chain remnants. It is concluded that plasmin resistance is a function of the intact structure and it is not directly dependent on the presence of the crosslink bonds or calcium ions."} {"id": "PMID:153767", "title": "Cross-linking of the (Ca2+ + Mg2+)-ATPase protein.", "content": "The addition of cupric-1,10,-phenanthroline, a cross-linking catalyst, to sarcoplasmic reticulum membranes caused protein sulfhydryl groups to form disulfide bridges. Following a short exposure to the catalyst (15 s, 22 degrees C) most of the protein was in a dimeric form (Mr = 248 000). Longer exposure times resulted in the formation of trimers, tetramers and other oligomers too large to enter the gel. At low temperatures (4 degrees C) dimer formation predominates even for exposure times as long as 5 min. Cross-linking in the presence of 7.5 mM Triton X-100 (a concentration that resulted in clearing of the membrane suspension and thus solubilization of the membrane components) showed the appearance of a considerable dimer fraction, however, most of the (Ca2+ + Mg2+)-ATPase protein appeared as a monomer. Following 1 min of cross-linking at 22 degrees C, freeze-etched membranes showed no alteration in the number or appearance of 80 A intramembranous particles. Thus extensive cross-linking of the (Ca2+ + Mg2+)-ATPase protein can occur without disruption of the normal position of the intramembrane portion of the molecule.", "contents": "Cross-linking of the (Ca2+ + Mg2+)-ATPase protein. The addition of cupric-1,10,-phenanthroline, a cross-linking catalyst, to sarcoplasmic reticulum membranes caused protein sulfhydryl groups to form disulfide bridges. Following a short exposure to the catalyst (15 s, 22 degrees C) most of the protein was in a dimeric form (Mr = 248 000). Longer exposure times resulted in the formation of trimers, tetramers and other oligomers too large to enter the gel. At low temperatures (4 degrees C) dimer formation predominates even for exposure times as long as 5 min. Cross-linking in the presence of 7.5 mM Triton X-100 (a concentration that resulted in clearing of the membrane suspension and thus solubilization of the membrane components) showed the appearance of a considerable dimer fraction, however, most of the (Ca2+ + Mg2+)-ATPase protein appeared as a monomer. Following 1 min of cross-linking at 22 degrees C, freeze-etched membranes showed no alteration in the number or appearance of 80 A intramembranous particles. Thus extensive cross-linking of the (Ca2+ + Mg2+)-ATPase protein can occur without disruption of the normal position of the intramembrane portion of the molecule."} {"id": "PMID:153768", "title": "Chemistry of heparitin sulfate and heparin from normal tissues and from patients with Hunter syndrome.", "content": "Some structural features of heparitin sulfate excreted by patients with Hunter syndrome are described. It is shown, with the aid of heparitinases and heparinase from Flavobacterium heparinum, that the Hunter heparitin sulfate is a very complex structure composed of nine different disaccharide units containing regions akin to normal heparitin sulfate and regions akin the heparin. Two-thirds of the iduronic acid residues of Hunter heparitin sulfate are devoid of sulfate, contrasting with heparin in which most of the iduronic acid residues are sulfated. The isolation and characterization of the non-reducing ends of heparin and of the heparitin sulfates is also described. Based on these results the specificity of the heparinase and heparitinases as well as the biosynthesis of iduronic acid-containing heparin-like compounds is discussed.", "contents": "Chemistry of heparitin sulfate and heparin from normal tissues and from patients with Hunter syndrome. Some structural features of heparitin sulfate excreted by patients with Hunter syndrome are described. It is shown, with the aid of heparitinases and heparinase from Flavobacterium heparinum, that the Hunter heparitin sulfate is a very complex structure composed of nine different disaccharide units containing regions akin to normal heparitin sulfate and regions akin the heparin. Two-thirds of the iduronic acid residues of Hunter heparitin sulfate are devoid of sulfate, contrasting with heparin in which most of the iduronic acid residues are sulfated. The isolation and characterization of the non-reducing ends of heparin and of the heparitin sulfates is also described. Based on these results the specificity of the heparinase and heparitinases as well as the biosynthesis of iduronic acid-containing heparin-like compounds is discussed."} {"id": "PMID:153769", "title": "[Esterase activity of the mitochondria oligomycin-sensitive ATPase complex].", "content": "It was found that mitochondrial oligomycin-sensitive ATPase (OS-ATPase) possesses the esterase activity with respect to some carboxylic acid esters with phenols and arylalcane alcohols. The substrate specificity of the esterase found was studied. The effects of some inhibitors and activators of ATPase on the enzyme activity were demonstrated. It was found that ADP inhibits the enzyme from submitochondrial particles containing factor F1 and does not inhibit the enzyme from the particles devoid of this factor. The data obtained suggest that esterase is localized in the hydrophobic part of the oligomycin-sensitive ATPase complex and are indicative of the functional interrelationship between the esterase and ATPase activities.", "contents": "[Esterase activity of the mitochondria oligomycin-sensitive ATPase complex]. It was found that mitochondrial oligomycin-sensitive ATPase (OS-ATPase) possesses the esterase activity with respect to some carboxylic acid esters with phenols and arylalcane alcohols. The substrate specificity of the esterase found was studied. The effects of some inhibitors and activators of ATPase on the enzyme activity were demonstrated. It was found that ADP inhibits the enzyme from submitochondrial particles containing factor F1 and does not inhibit the enzyme from the particles devoid of this factor. The data obtained suggest that esterase is localized in the hydrophobic part of the oligomycin-sensitive ATPase complex and are indicative of the functional interrelationship between the esterase and ATPase activities."} {"id": "PMID:153770", "title": "[Inhibition of mitochondrial ATPase by water-soluble carbodiimide].", "content": "Modification of the carboxyl group with pK 6,8-7,0 of isolated factor F1 by N-cyclohexyl-N'-beta-(4-xethylmorpholine) ethylcarbodiimide (CMCD) leads to the inhibition of the ATPase activity of the enzyme. The reaction rate of factor F1 with CMCD drops in the presence of ATP. It has been shown that during the first stage of the reaction reversible binding of CMCD with factor F1 occurs, forming a stable \"enzyme--inhibitor\" complex (Kdis=2.10(-4) M). N-cyclohexyl-N'-beta-(4-methylmorpholine) ethylcarbamide, a close analog of CMCD, is a competitive inhibitor of the ATPase reaction with Ki=9.10(-4) M. It is assumed that the carboxyl group, which reacts with CMCD, is located in the catalytic site of factor F1 and serves as the ligand of Me2+ in binding the substrate of the ATPase reaction Me-ATP. The reaction of factor F1, which was modified by CMCD, with proflavine, is accompanied by the covalent binding of the fluorescent label to the enzyme. The binding of proflavine to factor F1 leads to a sharp drop in the solubility of the enzyme in water.", "contents": "[Inhibition of mitochondrial ATPase by water-soluble carbodiimide]. Modification of the carboxyl group with pK 6,8-7,0 of isolated factor F1 by N-cyclohexyl-N'-beta-(4-xethylmorpholine) ethylcarbodiimide (CMCD) leads to the inhibition of the ATPase activity of the enzyme. The reaction rate of factor F1 with CMCD drops in the presence of ATP. It has been shown that during the first stage of the reaction reversible binding of CMCD with factor F1 occurs, forming a stable \"enzyme--inhibitor\" complex (Kdis=2.10(-4) M). N-cyclohexyl-N'-beta-(4-methylmorpholine) ethylcarbamide, a close analog of CMCD, is a competitive inhibitor of the ATPase reaction with Ki=9.10(-4) M. It is assumed that the carboxyl group, which reacts with CMCD, is located in the catalytic site of factor F1 and serves as the ligand of Me2+ in binding the substrate of the ATPase reaction Me-ATP. The reaction of factor F1, which was modified by CMCD, with proflavine, is accompanied by the covalent binding of the fluorescent label to the enzyme. The binding of proflavine to factor F1 leads to a sharp drop in the solubility of the enzyme in water."} {"id": "PMID:153771", "title": "[Purification and properties of plasminogen activator from human blood plasma after sudden death].", "content": "Plasminogen activator from human blood plasma after sudden death was isolated and purified 60-90-fold by precipitation with ammonium sulfate, ZnSO4 and ethanol as well as by chromatography on DEAE-Sephadex A-50 and gel--filtration through Sephadex G-200. The resulting enzyme had specific activity of 110-210 units per mg of protein. The enzyme prepartion possessed no plasmin activity; total content of carbohydrates was 2.4-2.5%; that of syalic acids--1.2-1.3%. The enzyme was found heterogeneous during disc electrophoresis in 7.0% polyacrylamide gel and corresponded in its mobility to beta-globulins of blood plasma. Molecular weight of enzyme as determined by gel-filtration through Sephadex G-200 is 70000. The isoelectric point lies at pH 6.2.", "contents": "[Purification and properties of plasminogen activator from human blood plasma after sudden death]. Plasminogen activator from human blood plasma after sudden death was isolated and purified 60-90-fold by precipitation with ammonium sulfate, ZnSO4 and ethanol as well as by chromatography on DEAE-Sephadex A-50 and gel--filtration through Sephadex G-200. The resulting enzyme had specific activity of 110-210 units per mg of protein. The enzyme prepartion possessed no plasmin activity; total content of carbohydrates was 2.4-2.5%; that of syalic acids--1.2-1.3%. The enzyme was found heterogeneous during disc electrophoresis in 7.0% polyacrylamide gel and corresponded in its mobility to beta-globulins of blood plasma. Molecular weight of enzyme as determined by gel-filtration through Sephadex G-200 is 70000. The isoelectric point lies at pH 6.2."} {"id": "PMID:153772", "title": "[Conformational changes in soluble mitochondrial ATPase by the spin probe method].", "content": "Modification of soluble mitochondrial ATPase (factor F1) by spin-labelled iodoacetamide and spin-labelled methyleneketone does not cause and change in the catalytic properties of the enzyme. The temperature dependence of tau corr. of labels bound to factor F1 testifies to conformational changes in the enzyme at temperatures of 18--20 degrees C and 34--37 degrees C. At these temperature intervals, breaks are observed in the temperature dependence of the ATPase reaction rate in the Arrenius plot. The results obtained indicate that the thermally induced conformational changes in factor F1 affect large areas of the protein molecule. The interaction of factor F1 with the hydrophobic spin probes, namely fatty acid derivatives, was studied. It was shown that the interaction of foctor F1 with Mg2+, Mg-ATP, Mg-ADP and ADP, results in an increase in the ability of the enzyme to adsorb spin probes.", "contents": "[Conformational changes in soluble mitochondrial ATPase by the spin probe method]. Modification of soluble mitochondrial ATPase (factor F1) by spin-labelled iodoacetamide and spin-labelled methyleneketone does not cause and change in the catalytic properties of the enzyme. The temperature dependence of tau corr. of labels bound to factor F1 testifies to conformational changes in the enzyme at temperatures of 18--20 degrees C and 34--37 degrees C. At these temperature intervals, breaks are observed in the temperature dependence of the ATPase reaction rate in the Arrenius plot. The results obtained indicate that the thermally induced conformational changes in factor F1 affect large areas of the protein molecule. The interaction of factor F1 with the hydrophobic spin probes, namely fatty acid derivatives, was studied. It was shown that the interaction of foctor F1 with Mg2+, Mg-ATP, Mg-ADP and ADP, results in an increase in the ability of the enzyme to adsorb spin probes."} {"id": "PMID:153773", "title": "Turnover of antiplasmin, the fast-acting plasmin inhibitor of plasma.", "content": "Human antiplasmin, the fast-acting plasmin inhibitor in plasma, was purified to homogeneity and labeled with 125I. This material, which was indistinguishable from antiplasmin in plasma with respect to several physicochemical and functional properties, was injected intravenously and its turnover measured in control subjects and in patients undergoing thrombolytic therapy. In eight control subjects (four healthy persons and four patients with atherosclerosis), the following turnover characteristics were obtained: plasma radioactivity half-life 2.64 +/- 0.32 days, fractional catabolic rate 0.53 +/- 0.09 of the plasma pool per day, intravascular fraction 0.51 +/- 0.05, and synthetic (catabolic) rate 1.4 +/- 0.27 mg/kg/day. The half-life of the plasmin-antiplasmin complex in plasma, measured from the disappearance rate of labeled antiplasmin, plasmin or plasmin-antiplasmin complex during thrombolytic therapy was approximately 0.5 days.", "contents": "Turnover of antiplasmin, the fast-acting plasmin inhibitor of plasma. Human antiplasmin, the fast-acting plasmin inhibitor in plasma, was purified to homogeneity and labeled with 125I. This material, which was indistinguishable from antiplasmin in plasma with respect to several physicochemical and functional properties, was injected intravenously and its turnover measured in control subjects and in patients undergoing thrombolytic therapy. In eight control subjects (four healthy persons and four patients with atherosclerosis), the following turnover characteristics were obtained: plasma radioactivity half-life 2.64 +/- 0.32 days, fractional catabolic rate 0.53 +/- 0.09 of the plasma pool per day, intravascular fraction 0.51 +/- 0.05, and synthetic (catabolic) rate 1.4 +/- 0.27 mg/kg/day. The half-life of the plasmin-antiplasmin complex in plasma, measured from the disappearance rate of labeled antiplasmin, plasmin or plasmin-antiplasmin complex during thrombolytic therapy was approximately 0.5 days."} {"id": "PMID:153774", "title": "Nature of the calcium regulatory system of bovine arterial actomyosin.", "content": "A calcium-sensitive actomyosin was prepared from bovine aortic muscularis. The results of applying filament displacement tests indicate that bovine arterial actomyosin possesses predominantly a calcium regulatory system associated with the myosin filament, but also may possess a calcium regulatory system associated with the filament. Calcium binding to highly purified myosin preparations could not account for the calcium binding to calcium-sensitive actomyosin. A calcium-insensitive actomyosin preparation, prepared by omitting dithiothreitol from the isolation procedure, showed a definite loss of tropomyosin but no change in calcium binding relative to the calcium-sensitive actomyosin.", "contents": "Nature of the calcium regulatory system of bovine arterial actomyosin. A calcium-sensitive actomyosin was prepared from bovine aortic muscularis. The results of applying filament displacement tests indicate that bovine arterial actomyosin possesses predominantly a calcium regulatory system associated with the myosin filament, but also may possess a calcium regulatory system associated with the filament. Calcium binding to highly purified myosin preparations could not account for the calcium binding to calcium-sensitive actomyosin. A calcium-insensitive actomyosin preparation, prepared by omitting dithiothreitol from the isolation procedure, showed a definite loss of tropomyosin but no change in calcium binding relative to the calcium-sensitive actomyosin."} {"id": "PMID:153779", "title": "[Hormonal dynamics during pregnancy: critical discussion and clinical interpretations].", "content": "Although the clinical interpretation of its results varies greatly among perinatologists, the dehydroepiandrosterone sulfate (DHEA-S) loading test has become an integral part of fetal monitoring in many centres dealing with high-risk pregnancies. Currently four main metabolic responses to administration of DHEA-S to the mother are monitored to predict the functional state of the fetoplacental unit: the metabolic clearance of DHEA-S, the metabolic clearance of DHEA-S into estradiol, the conversion of DHEA-S into estradiol or esterol, and the increase in the plasma concentrations of DHEA and androstenedione after administration of DHEA-S. This article critically reviews each of these responses and its possible clinical interpretation, and assesses the clinical future of the DHEA-S loading test.", "contents": "[Hormonal dynamics during pregnancy: critical discussion and clinical interpretations]. Although the clinical interpretation of its results varies greatly among perinatologists, the dehydroepiandrosterone sulfate (DHEA-S) loading test has become an integral part of fetal monitoring in many centres dealing with high-risk pregnancies. Currently four main metabolic responses to administration of DHEA-S to the mother are monitored to predict the functional state of the fetoplacental unit: the metabolic clearance of DHEA-S, the metabolic clearance of DHEA-S into estradiol, the conversion of DHEA-S into estradiol or esterol, and the increase in the plasma concentrations of DHEA and androstenedione after administration of DHEA-S. This article critically reviews each of these responses and its possible clinical interpretation, and assesses the clinical future of the DHEA-S loading test."} {"id": "PMID:153786", "title": "In vitro functional studies of mononuclear cells in patients with CLL: evidence for functionally normal T lymphocytes and monocytes and abnormal B lymphocytes.", "content": "In vitro functional studies of mononuclear cells from 34 patients with B-cell type CLL were investigated and the results of these studies were as follows: 1) The T lymphocytes from patients with CLL were capable of responding normally to PHA or PWM, of inducing allogeneic normal B lymphocytes to respond to these mitogens and of stimulating normally to allogeneic lymphocytes in \"one-way\" mixed lymphocyte reaction; 2) The monocytes from these patients were capable of enhancing the T lymphocyte response to mitogens and of stimulating normally to allogeneic lymphocytes; and 3) The leukemic B lymphocytes were incapable of responding to mitogens even in the presence of normal T lymphocytes and their enhancer cell activity on T lymphocyte response or their stimulating capacity on allogeneic lymphocytes was depressed. These observations suggest that the T lymphocytes and monocytes from patients with CLL are functionally normal while the leukemic B lymphocytes from these patients are functionally abnormal.", "contents": "In vitro functional studies of mononuclear cells in patients with CLL: evidence for functionally normal T lymphocytes and monocytes and abnormal B lymphocytes. In vitro functional studies of mononuclear cells from 34 patients with B-cell type CLL were investigated and the results of these studies were as follows: 1) The T lymphocytes from patients with CLL were capable of responding normally to PHA or PWM, of inducing allogeneic normal B lymphocytes to respond to these mitogens and of stimulating normally to allogeneic lymphocytes in \"one-way\" mixed lymphocyte reaction; 2) The monocytes from these patients were capable of enhancing the T lymphocyte response to mitogens and of stimulating normally to allogeneic lymphocytes; and 3) The leukemic B lymphocytes were incapable of responding to mitogens even in the presence of normal T lymphocytes and their enhancer cell activity on T lymphocyte response or their stimulating capacity on allogeneic lymphocytes was depressed. These observations suggest that the T lymphocytes and monocytes from patients with CLL are functionally normal while the leukemic B lymphocytes from these patients are functionally abnormal."} {"id": "PMID:153787", "title": "Comparative trial of low-dose adriamycin plus cyclophosphamide with or without additive hormonal therapy in advanced breast cancer.", "content": "We treated 56 women with advanced metastatic breast cancer who had not received prior chemotherapy in a comparative trial of cytotoxic chemotherapy with low-dose adriamycin plus cyclophosphamide alone or in combination with the androgenic steroid calusterone. The response rate to chemohormonal therapy (65%) could not be shown to be statistically better than that for chemotherapy alone (53%) for this size patient population. However, the median remission duration (21.5 months) was significantly prolonged over the 11.5-month remission duration for chemotherapy alone (p = 0.03). The median survival of the chemohormonal therapy group was 23.5 months, whereas that for chemotherapy alone was 13.5 months (p = 0.05). These results indicate that the addition of a potent hormonal agent to effective cytotoxic chemotherapy improves the results of treatment of women with metastatic breast cancer.", "contents": "Comparative trial of low-dose adriamycin plus cyclophosphamide with or without additive hormonal therapy in advanced breast cancer. We treated 56 women with advanced metastatic breast cancer who had not received prior chemotherapy in a comparative trial of cytotoxic chemotherapy with low-dose adriamycin plus cyclophosphamide alone or in combination with the androgenic steroid calusterone. The response rate to chemohormonal therapy (65%) could not be shown to be statistically better than that for chemotherapy alone (53%) for this size patient population. However, the median remission duration (21.5 months) was significantly prolonged over the 11.5-month remission duration for chemotherapy alone (p = 0.03). The median survival of the chemohormonal therapy group was 23.5 months, whereas that for chemotherapy alone was 13.5 months (p = 0.05). These results indicate that the addition of a potent hormonal agent to effective cytotoxic chemotherapy improves the results of treatment of women with metastatic breast cancer."} {"id": "PMID:153790", "title": "Immunity to cell surface antigens and immune complex glomerulonephritis in hamsters bearing human epithelial tumors.", "content": "A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularity, electron-dense mesangial deposits, and mesangial deposits of immunoglobulin G and C'3. Renal eluates obtained from the tumor-bearing animals contained substantial amounts of immunoglobulins. Our immunopathological studies demonstrated that virtually all of the eluate immunoglobulin G was tumor-specific antibody directed exclusively against surface determinants of the MA160 cells. There was no demonstrable activity against cytoplasmic or nuclear constituents of the MA160 cells or against certain hamster antigenic determinants. The antibody in the eluate could be removed by repetitive absorptions with viable MA160 cells but not with similar absorptions with either normal human diploid fibroblasts, human heteroploid HeLa cells, or BHK21 hamster cells. Our data support the concept of a specific nephritogenic immunopathological process occurring as a result of immunity to tumor-specific surface determinants.", "contents": "Immunity to cell surface antigens and immune complex glomerulonephritis in hamsters bearing human epithelial tumors. A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularity, electron-dense mesangial deposits, and mesangial deposits of immunoglobulin G and C'3. Renal eluates obtained from the tumor-bearing animals contained substantial amounts of immunoglobulins. Our immunopathological studies demonstrated that virtually all of the eluate immunoglobulin G was tumor-specific antibody directed exclusively against surface determinants of the MA160 cells. There was no demonstrable activity against cytoplasmic or nuclear constituents of the MA160 cells or against certain hamster antigenic determinants. The antibody in the eluate could be removed by repetitive absorptions with viable MA160 cells but not with similar absorptions with either normal human diploid fibroblasts, human heteroploid HeLa cells, or BHK21 hamster cells. Our data support the concept of a specific nephritogenic immunopathological process occurring as a result of immunity to tumor-specific surface determinants."} {"id": "PMID:153793", "title": "Restrictive cardiomyopathy in an infant with massive biatrial enlargement and normal ventricular size and pump function.", "content": "Restrictive cardiomyopathy in an infant with massive biatrial enlargement and normal ventricular size has been reported only once previously [3]. We now present a 13-month-old patient with severe and progressive congestive heart failure who demonstrated normal ventricular cavity size with biatrial enlargement. Ejection fraction and echocardiographic ventricular function studies were normal.", "contents": "Restrictive cardiomyopathy in an infant with massive biatrial enlargement and normal ventricular size and pump function. Restrictive cardiomyopathy in an infant with massive biatrial enlargement and normal ventricular size has been reported only once previously [3]. We now present a 13-month-old patient with severe and progressive congestive heart failure who demonstrated normal ventricular cavity size with biatrial enlargement. Ejection fraction and echocardiographic ventricular function studies were normal."} {"id": "PMID:153803", "title": "Certification of smallpox eradication.", "content": "The world's last known case of smallpox resulting from human-to-human transmission in an endemic focus occurred in Somalia in October 1977, and there remains the task of documenting the global eradication of the disease and establishing the safety of vaccination. Those countries as yet uncertified have been grouped into four categories according to the procedures recommended for their certification. An important criterion for deciding the type of procedure is how recently smallpox was endemic in a particular country. This paper is concerned with those countries in which the disease has been nonendemic for some years but which have not yet received certification of eradication. One such country is Burma, which was certified free of smallpox in 1977, some 8 years after its last reported case but 2 years after the last case in Bangladesh, with which it shares a long frontier. The procedures used in Burma and the lessons that were learnt therefrom are described.", "contents": "Certification of smallpox eradication. The world's last known case of smallpox resulting from human-to-human transmission in an endemic focus occurred in Somalia in October 1977, and there remains the task of documenting the global eradication of the disease and establishing the safety of vaccination. Those countries as yet uncertified have been grouped into four categories according to the procedures recommended for their certification. An important criterion for deciding the type of procedure is how recently smallpox was endemic in a particular country. This paper is concerned with those countries in which the disease has been nonendemic for some years but which have not yet received certification of eradication. One such country is Burma, which was certified free of smallpox in 1977, some 8 years after its last reported case but 2 years after the last case in Bangladesh, with which it shares a long frontier. The procedures used in Burma and the lessons that were learnt therefrom are described."} {"id": "PMID:153804", "title": "Control of trachoma and prevention of blindness in rural communities in Burma.", "content": "Trachoma was identified as the single most important cause of blindness in central Burma in a study carried out in 1961-1962. Control measures started in 1964 considerably reduced the degree of endemicity and severity of the disease in the areas treated. According to recent simplified criteria of evaluation, the prevalence of active trachoma has been reduced by more than 60% and that of active inflammatory disease of moderate and severe intensity from 7.4% to 1.8% of the active cases. A reduction in the risk of becoming infected is evident from changes that have occurred among the younger age groups.The experience acquired by the trachoma control project in central Burma-covering a population of more than 4 million in 8000 villages-emphasizes the importance of the active participation of the community and the role of local auxiliary personnel. Most of the activities, including surgical repair of trichiasis, are the responsibility of health assistants; their training includes, in addition to the recognition and treatment of patients requiring topical application of antibiotics or surgical repair of trichiasis, the screening and referral to the general practitioner or to the eye specialist of those needing more specialized attention.The results already obtained have made possible a gradual replacement of control activities by a surveillance programme, and their integration into the basic health services. The objectives of the trachoma control programme have been expanded to include the prevention and management of other causes of preventable or curable blindness, with special emphasis on eye injuries and glaucoma.", "contents": "Control of trachoma and prevention of blindness in rural communities in Burma. Trachoma was identified as the single most important cause of blindness in central Burma in a study carried out in 1961-1962. Control measures started in 1964 considerably reduced the degree of endemicity and severity of the disease in the areas treated. According to recent simplified criteria of evaluation, the prevalence of active trachoma has been reduced by more than 60% and that of active inflammatory disease of moderate and severe intensity from 7.4% to 1.8% of the active cases. A reduction in the risk of becoming infected is evident from changes that have occurred among the younger age groups.The experience acquired by the trachoma control project in central Burma-covering a population of more than 4 million in 8000 villages-emphasizes the importance of the active participation of the community and the role of local auxiliary personnel. Most of the activities, including surgical repair of trichiasis, are the responsibility of health assistants; their training includes, in addition to the recognition and treatment of patients requiring topical application of antibiotics or surgical repair of trichiasis, the screening and referral to the general practitioner or to the eye specialist of those needing more specialized attention.The results already obtained have made possible a gradual replacement of control activities by a surveillance programme, and their integration into the basic health services. The objectives of the trachoma control programme have been expanded to include the prevention and management of other causes of preventable or curable blindness, with special emphasis on eye injuries and glaucoma."} {"id": "PMID:153807", "title": "Instantaneous transmitral blood flow and anterior mitral leaflet motion in man.", "content": "Transmitral blood flow was measured in man by numerical differentiation of left ventricular volume as a function of time in 11 patients undergoing cardiac catheterization. Using this technique, transmitral blood flow may be studied in a variety of pathologic states without the need for surgically introduced flowmeters. Just before left ventriculography, echocardiography of the mitral valve was performed. The pattern of transmitral blood flow was strikingly similar to the diastolic movement of the anterior mitral leaflet. At any equivalent diastolic filling time, the percent of the integrated area beneath the curve inscribed by the diastolic anterior mirtal leaflet echoes closely approximated the percent of stroke volume which had entered the left ventricle. This observation supports the hypothesis that mitral leaflet motion accurately reflects transmitral flow. Consequently, at a given time during diastole, the relative velocity of transmitral flow and the percent of the stroke volume which has entered the left ventricle may be approximated noninvasively from the anterior mitral leaflet echogram.", "contents": "Instantaneous transmitral blood flow and anterior mitral leaflet motion in man. Transmitral blood flow was measured in man by numerical differentiation of left ventricular volume as a function of time in 11 patients undergoing cardiac catheterization. Using this technique, transmitral blood flow may be studied in a variety of pathologic states without the need for surgically introduced flowmeters. Just before left ventriculography, echocardiography of the mitral valve was performed. The pattern of transmitral blood flow was strikingly similar to the diastolic movement of the anterior mitral leaflet. At any equivalent diastolic filling time, the percent of the integrated area beneath the curve inscribed by the diastolic anterior mirtal leaflet echoes closely approximated the percent of stroke volume which had entered the left ventricle. This observation supports the hypothesis that mitral leaflet motion accurately reflects transmitral flow. Consequently, at a given time during diastole, the relative velocity of transmitral flow and the percent of the stroke volume which has entered the left ventricle may be approximated noninvasively from the anterior mitral leaflet echogram."} {"id": "PMID:153802", "title": "[Beckwith Wiedemann syndrom (author's transl)].", "content": "In connection with four new observations and a revue of 82 cases published the mains features of Beckwith-Wiedeman syndrom are described insisting on the neonatal troubles of the glycoregulation upon the structural development of the childrens and on the pathologics associations.", "contents": "[Beckwith Wiedemann syndrom (author's transl)]. In connection with four new observations and a revue of 82 cases published the mains features of Beckwith-Wiedeman syndrom are described insisting on the neonatal troubles of the glycoregulation upon the structural development of the childrens and on the pathologics associations."} {"id": "PMID:153809", "title": "Prenatal monitoring for the Hunter syndrome: the heterozygous female fetus.", "content": "An abnormal level of 35S-sulfate labeled mucopolysaccharides was found in cultured amniotic fluid cells from a pregnancy, at risk for the Hunter syndrome, with a female fetal karyotype. Subsequent prenatal analyses suggested heterozygosity for the X-linked Hunter syndrome, and this was confirmed by clonal analysis of fibroblasts of the child after birth. The possible implications of abnormal biochemical results in association with a female karyotype in the prenatal diagnosis of the Hunter syndrome are discussed.", "contents": "Prenatal monitoring for the Hunter syndrome: the heterozygous female fetus. An abnormal level of 35S-sulfate labeled mucopolysaccharides was found in cultured amniotic fluid cells from a pregnancy, at risk for the Hunter syndrome, with a female fetal karyotype. Subsequent prenatal analyses suggested heterozygosity for the X-linked Hunter syndrome, and this was confirmed by clonal analysis of fibroblasts of the child after birth. The possible implications of abnormal biochemical results in association with a female karyotype in the prenatal diagnosis of the Hunter syndrome are discussed."} {"id": "PMID:153814", "title": "The use of laparoscopy in gynaecology.", "content": "Diagnostic laparoscopy is of most value in the evaluation of infertility and for completing the gynaecological investigation of obscure cases of chronic pelvic pain. Its use to exclude ectopic pregnancy, salpingitis and pelvic cancer is more controversial. The management of some cases of primary amenorrhoea is aided by laparoscopic gonadal biopsy. The excessive demand for female sterilization will ensure that the laparoscope continues to be used for this purpose and is leading to a compromise. The surgical techniques which have been proved to be most effective are being replaced by methods favoured for their potential reversibility and rapid patient turn-over. If all our laparoscopes were abandoned, gynaecological surgery would perhaps not suffer a major setback, but, for the present, those who neglect laparoscopy are losing an important dimension of modern practice.", "contents": "The use of laparoscopy in gynaecology. Diagnostic laparoscopy is of most value in the evaluation of infertility and for completing the gynaecological investigation of obscure cases of chronic pelvic pain. Its use to exclude ectopic pregnancy, salpingitis and pelvic cancer is more controversial. The management of some cases of primary amenorrhoea is aided by laparoscopic gonadal biopsy. The excessive demand for female sterilization will ensure that the laparoscope continues to be used for this purpose and is leading to a compromise. The surgical techniques which have been proved to be most effective are being replaced by methods favoured for their potential reversibility and rapid patient turn-over. If all our laparoscopes were abandoned, gynaecological surgery would perhaps not suffer a major setback, but, for the present, those who neglect laparoscopy are losing an important dimension of modern practice."} {"id": "PMID:153815", "title": "Hearing loss in Down's syndrome. A treatable handicap more common than generally recognized.", "content": "Significant hearing loss was found in about two-thirds of a series of 107 individuals with Down's syndrome. Hearing loss of that degree causes retardation of speech, language and intellectual development in normal children. Down's children are presumably affected even more by this sensory deprivation and without correction are prevented from reaching their full potential.", "contents": "Hearing loss in Down's syndrome. A treatable handicap more common than generally recognized. Significant hearing loss was found in about two-thirds of a series of 107 individuals with Down's syndrome. Hearing loss of that degree causes retardation of speech, language and intellectual development in normal children. Down's children are presumably affected even more by this sensory deprivation and without correction are prevented from reaching their full potential."} {"id": "PMID:153820", "title": "Photocontact dermatitis to hydrocortisone.", "content": "A patient was found to have a delayed positive patch test to hydrocortisone on multiple testing. This proved to be due to a photoallergy with an action spectrum in the UV-A range. The patient coincidently had a polymorphous light eruption in the UV-B range.", "contents": "Photocontact dermatitis to hydrocortisone. A patient was found to have a delayed positive patch test to hydrocortisone on multiple testing. This proved to be due to a photoallergy with an action spectrum in the UV-A range. The patient coincidently had a polymorphous light eruption in the UV-B range."} {"id": "PMID:153821", "title": "Coolant oil dermatitis due to ethylenediamine.", "content": "Two outbreaks of hand dermatitis in light engineering works are reported. In both cases a number of workers shown to be allergic to soluble coolant oils were found to be allergic to ethylenediamine, which had either been incorporated into the oil or had been added to it later.", "contents": "Coolant oil dermatitis due to ethylenediamine. Two outbreaks of hand dermatitis in light engineering works are reported. In both cases a number of workers shown to be allergic to soluble coolant oils were found to be allergic to ethylenediamine, which had either been incorporated into the oil or had been added to it later."} {"id": "PMID:153829", "title": "Asymmetric septal hypertrophy in patients on long-term hemodialysis.", "content": "Echocardiographic studies were performed in 23 hypertensive patients who were receiving therapy with long-term hemodialysis. Five patients (22 percent) had normal thickness of the left ventricular wall. Eleven (48 percent) had symmetric left ventricular hypertrophy, and seven (30 percent) showed asymmetric septal hypertrophy, with a ratio of septal to posterior wall thickness of 1.3 or greater. The latter group differed from patients with hypertrophic cardiomyopathy in that patients on long-term hemodialysis had a dilated left ventricular dimension, a relatively normal diastolic slope of the mitral valve, absence of systolic motion of the mitral valve, and a septal to posterior wall ratio of less than 1.5. A high incidence of asymmetric septal hypertrophy in this and other studies indicates that this condition is not specific for hypertrophic cardiomyopathy. We suggest that in addition to asymmetric septal hypertrophy, the diagnosis of hypertrophic cardiomyopathy should be made in the light of the clinical picture, as well as other echocardiographic features.", "contents": "Asymmetric septal hypertrophy in patients on long-term hemodialysis. Echocardiographic studies were performed in 23 hypertensive patients who were receiving therapy with long-term hemodialysis. Five patients (22 percent) had normal thickness of the left ventricular wall. Eleven (48 percent) had symmetric left ventricular hypertrophy, and seven (30 percent) showed asymmetric septal hypertrophy, with a ratio of septal to posterior wall thickness of 1.3 or greater. The latter group differed from patients with hypertrophic cardiomyopathy in that patients on long-term hemodialysis had a dilated left ventricular dimension, a relatively normal diastolic slope of the mitral valve, absence of systolic motion of the mitral valve, and a septal to posterior wall ratio of less than 1.5. A high incidence of asymmetric septal hypertrophy in this and other studies indicates that this condition is not specific for hypertrophic cardiomyopathy. We suggest that in addition to asymmetric septal hypertrophy, the diagnosis of hypertrophic cardiomyopathy should be made in the light of the clinical picture, as well as other echocardiographic features."} {"id": "PMID:153830", "title": "Loculated interlobar air-fluid collection in congestive heart failure.", "content": "Two patients are described who had congestive heart failure with loculated interlobar air-fluid collections. Although pseudotumor (interlobar effusion) is a well-known finding in congestive heart failure, the additional presence of air is unique. Both are somewhat related to the underlying failure.", "contents": "Loculated interlobar air-fluid collection in congestive heart failure. Two patients are described who had congestive heart failure with loculated interlobar air-fluid collections. Although pseudotumor (interlobar effusion) is a well-known finding in congestive heart failure, the additional presence of air is unique. Both are somewhat related to the underlying failure."} {"id": "PMID:153832", "title": "Mirrow reactions of Down's syndrome infants and toddlers: cognitive underpinnings of self-recognition.", "content": "To examine the developmental significance of mirrow self-recognition in early childhood, a cross-sectional study with 55 Down's syndrome children was conducted. When their image is altered by rouge on the nose, normal infants by 22 months indicate self-recognition by touching their noses while looking in the mirror. Only a small percentage of Down's syndrome children touched their noses by this age, confirming the expected lag in this development. However, those young Down's syndrome infants with near-normal development quotient did manifest the reaction. In general, when developmental age was equated, the Down's syndrome children showed parallel development to normal children.", "contents": "Mirrow reactions of Down's syndrome infants and toddlers: cognitive underpinnings of self-recognition. To examine the developmental significance of mirrow self-recognition in early childhood, a cross-sectional study with 55 Down's syndrome children was conducted. When their image is altered by rouge on the nose, normal infants by 22 months indicate self-recognition by touching their noses while looking in the mirror. Only a small percentage of Down's syndrome children touched their noses by this age, confirming the expected lag in this development. However, those young Down's syndrome infants with near-normal development quotient did manifest the reaction. In general, when developmental age was equated, the Down's syndrome children showed parallel development to normal children."} {"id": "PMID:153835", "title": "A new biochemical subtype of the Sanfilippo syndrome: characterization of the storage material in cultured fibroblasts of Sanfilippo C patients.", "content": "Fibroblasts cultured from the skin of three unrelated patients with the clinical symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated intracellularly excessive amounts of heparan sulfate and showed a lengthened turnover time for this mucopolysaccharide. They exhibited, however, neither a deficiency of heparan sulfate sulfamidase or alpha-N-acetylglucosaminidase nor of any other known glycosaminoglycan-degrading hydrolase. This new mucopolysaccharidosis was therefore designated as type C of the Sanfilippo syndrome. The abnormal heparan sulfate metabolism of Sanfilippo C fibroblasts could not be normalized by addition of crude urinary proteins or concentrated secretions from normal fibroblasts to the culture medium or by cocultivation with normal fibroblasts. The accumulated heparan sulfate was characterized by a reduced negative net charge. A small proportion of it could be adsorbed onto a cation exchange resin. It was sensitive to nitrous acid degradation under conditions where glucosamine residues with free amino groups are attacked. It is therefore suggested that the primary defect in this new mucopolysaccharidosis concerns the step which follows the hydrolysis of N-sulfonate groups in heparan sulfate degradation.", "contents": "A new biochemical subtype of the Sanfilippo syndrome: characterization of the storage material in cultured fibroblasts of Sanfilippo C patients. Fibroblasts cultured from the skin of three unrelated patients with the clinical symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated intracellularly excessive amounts of heparan sulfate and showed a lengthened turnover time for this mucopolysaccharide. They exhibited, however, neither a deficiency of heparan sulfate sulfamidase or alpha-N-acetylglucosaminidase nor of any other known glycosaminoglycan-degrading hydrolase. This new mucopolysaccharidosis was therefore designated as type C of the Sanfilippo syndrome. The abnormal heparan sulfate metabolism of Sanfilippo C fibroblasts could not be normalized by addition of crude urinary proteins or concentrated secretions from normal fibroblasts to the culture medium or by cocultivation with normal fibroblasts. The accumulated heparan sulfate was characterized by a reduced negative net charge. A small proportion of it could be adsorbed onto a cation exchange resin. It was sensitive to nitrous acid degradation under conditions where glucosamine residues with free amino groups are attacked. It is therefore suggested that the primary defect in this new mucopolysaccharidosis concerns the step which follows the hydrolysis of N-sulfonate groups in heparan sulfate degradation."} {"id": "PMID:153853", "title": "Alterations in the cardiovascular system that occur in advanced age.", "content": "Recent information appears to solidify the concept that the left ventricle hypertrophies with age in normal adult man. The stimulus for this moderate increase in wall thickness has not been precisely determined but an attractive hypothesis suggests that the stimulus may be an increased load imposed by the peripheral vascular resistance. The mechanism for the well-documented diminished cardiovascular response to maximal exercise in normal aged man still remains unclear. Evidence in the canine model indicates that a diminished chronotropic response to catecholamines could in part explain a limitation in maximal heart rate response. The reflex change in heart rate in respone to hypercapnia, hypoxia, and sustained isometric handgrip in normal man is diminished with age. The precise mechanism of this age-associated phenomenon remains to be elucidated, but the chronotropic responsiveness to catecholamines is likely a contributing factor. Finally, there is evidence of slowed myocardial relaxation in hearts of aged animals and man. A decrement in the speed at which the sarcoplasmic reticulum from hearts of aged rats accumulates calcium has been demonstrated and appears to be involved in the mechanism of prolonged contraction in aged myocardium.", "contents": "Alterations in the cardiovascular system that occur in advanced age. Recent information appears to solidify the concept that the left ventricle hypertrophies with age in normal adult man. The stimulus for this moderate increase in wall thickness has not been precisely determined but an attractive hypothesis suggests that the stimulus may be an increased load imposed by the peripheral vascular resistance. The mechanism for the well-documented diminished cardiovascular response to maximal exercise in normal aged man still remains unclear. Evidence in the canine model indicates that a diminished chronotropic response to catecholamines could in part explain a limitation in maximal heart rate response. The reflex change in heart rate in respone to hypercapnia, hypoxia, and sustained isometric handgrip in normal man is diminished with age. The precise mechanism of this age-associated phenomenon remains to be elucidated, but the chronotropic responsiveness to catecholamines is likely a contributing factor. Finally, there is evidence of slowed myocardial relaxation in hearts of aged animals and man. A decrement in the speed at which the sarcoplasmic reticulum from hearts of aged rats accumulates calcium has been demonstrated and appears to be involved in the mechanism of prolonged contraction in aged myocardium."} {"id": "PMID:153862", "title": "Effect of benzoyl peroxide on skin surface lipids.", "content": "Investigations have been performed on the effect of benzoyl peroxide on skin surface lipids by direct lipid extraction with petrol ether and quantitative determination. Though there was no change after 1 week treatment, after 4 weeks a significant reduction of the casual level as well as well as the replacement sum could be observed.", "contents": "Effect of benzoyl peroxide on skin surface lipids. Investigations have been performed on the effect of benzoyl peroxide on skin surface lipids by direct lipid extraction with petrol ether and quantitative determination. Though there was no change after 1 week treatment, after 4 weeks a significant reduction of the casual level as well as well as the replacement sum could be observed."} {"id": "PMID:153863", "title": "Oral treatment of pustulosis palmo-plantaris with a new retinoid, Ro 10-9359.", "content": "Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Earlier clinical experience has proved Ro 10-9359 to be an extremely potent antipsoriatic drug. The well-known association between psoriasis and pustulosis palmoplantaris was a motivation to evaluate Ro 10-9359 also in the last-mentioned disease, which is notoriously known to be resistant to treatment. In this study 30 patients were given either 75 mg/day of Ro 10-9359 or 200 mg twice every week according to a randomized pattern. All patients had suffered from the disease for at least 2 years without any spontaneous remission during the year preceding the trial. After a treatment period of about 2 weeks with Ro 10-9359 hyperkeratotic scales had usually disappeared, and 2 weeks later there were in general significantly less pustular lesions. The treatment continued for 8 weeks, and at this time the average reduction of the number of pustules was 80%. The daily dosage seemed to give better results and was also better tolerated than was the twice-weekly dosage. Side effects were common, but generally mild. On average, the remission lasted 1 month after cessation of therapy.", "contents": "Oral treatment of pustulosis palmo-plantaris with a new retinoid, Ro 10-9359. Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Earlier clinical experience has proved Ro 10-9359 to be an extremely potent antipsoriatic drug. The well-known association between psoriasis and pustulosis palmoplantaris was a motivation to evaluate Ro 10-9359 also in the last-mentioned disease, which is notoriously known to be resistant to treatment. In this study 30 patients were given either 75 mg/day of Ro 10-9359 or 200 mg twice every week according to a randomized pattern. All patients had suffered from the disease for at least 2 years without any spontaneous remission during the year preceding the trial. After a treatment period of about 2 weeks with Ro 10-9359 hyperkeratotic scales had usually disappeared, and 2 weeks later there were in general significantly less pustular lesions. The treatment continued for 8 weeks, and at this time the average reduction of the number of pustules was 80%. The daily dosage seemed to give better results and was also better tolerated than was the twice-weekly dosage. Side effects were common, but generally mild. On average, the remission lasted 1 month after cessation of therapy."} {"id": "PMID:153864", "title": "[Multiple granulomata pyogenica in a patient with acne vulgaris (author's transl)].", "content": "Multiple granulomata pyogenica are usually satellites of a primary lesion recently treated unsuccessfully. Disseminated pyogenic granulomas are very uncommon. In our case report, we describe a young man with six granulomata pyogenica over the chest, after treating his acne with tetracycline and vitamin A acid. In the discussion, we include infection, trauma and vitamin A acid as factors which can induce the vascular tumor in the region of a vascular dysplasia.", "contents": "[Multiple granulomata pyogenica in a patient with acne vulgaris (author's transl)]. Multiple granulomata pyogenica are usually satellites of a primary lesion recently treated unsuccessfully. Disseminated pyogenic granulomas are very uncommon. In our case report, we describe a young man with six granulomata pyogenica over the chest, after treating his acne with tetracycline and vitamin A acid. In the discussion, we include infection, trauma and vitamin A acid as factors which can induce the vascular tumor in the region of a vascular dysplasia."} {"id": "PMID:153870", "title": "Subcutaneous emphysema of the abdominal wall from diverticulitis with necrotizing fasciitis.", "content": "The case history of a patient with subcutaneous emphysema of the abdomen from sigmoid diverticulitis is presented. The mechanisms for developing abdominal wall emphysema are reviewed. Thus when the gas originates from the gastrointestinal tract, mechanical factors are mainly responsible for this phenomenon. These inculde a direct communication through a colonocutaneous fistula. Gas may, however, also be spread into the abdominal wall by high intraintestinal pressures. Infection with gas-producing organisms may be associated with subcutaneous emphysema. This is particularly true when the emphysema develops 48 h or longer after onset of symptoms. Infection, however, is not the major cause for gas in these tissues.", "contents": "Subcutaneous emphysema of the abdominal wall from diverticulitis with necrotizing fasciitis. The case history of a patient with subcutaneous emphysema of the abdomen from sigmoid diverticulitis is presented. The mechanisms for developing abdominal wall emphysema are reviewed. Thus when the gas originates from the gastrointestinal tract, mechanical factors are mainly responsible for this phenomenon. These inculde a direct communication through a colonocutaneous fistula. Gas may, however, also be spread into the abdominal wall by high intraintestinal pressures. Infection with gas-producing organisms may be associated with subcutaneous emphysema. This is particularly true when the emphysema develops 48 h or longer after onset of symptoms. Infection, however, is not the major cause for gas in these tissues."} {"id": "PMID:153886", "title": "Comparison of thymidine, fluorodeoxyuridine, hydroxyurea, and methotrexate blocking at the G1/S phase transition of the cell cycle, studied by replication patterns.", "content": "Cultures of human amniotic fluid cells and fibroblasts were temporarily blocked by the replication inhibitors thymidine (dT) surplus, fluorodeoxyuridine (FdU), hydroxyurea (HU), or methotrexate uridine (MU). The respective arresting point at G1-S transition and the homogeneity of the blocked cell population were determined by means of BrdU replication patterns. Most variation of patterns were found after HU. After MU, cells were arrested before the onset of replication, while with dT surplus of FdU an arresting point in early S seemed more likely.", "contents": "Comparison of thymidine, fluorodeoxyuridine, hydroxyurea, and methotrexate blocking at the G1/S phase transition of the cell cycle, studied by replication patterns. Cultures of human amniotic fluid cells and fibroblasts were temporarily blocked by the replication inhibitors thymidine (dT) surplus, fluorodeoxyuridine (FdU), hydroxyurea (HU), or methotrexate uridine (MU). The respective arresting point at G1-S transition and the homogeneity of the blocked cell population were determined by means of BrdU replication patterns. Most variation of patterns were found after HU. After MU, cells were arrested before the onset of replication, while with dT surplus of FdU an arresting point in early S seemed more likely."} {"id": "PMID:153887", "title": "Unstable telocentric chromosome produced after centric misdivision of a 21q/21q translocated element.", "content": "An unstable telocentric chromosome was found in an individual with Down's syndrome and an unusual chromosomal mosaic, 46,XX, t(21q21q)+,21-/46,XX,21q-/45,XX,21-. As the 21q/21q chromosome was of paternal origin, based on the characteristics of its centromeric heterochromatin and on the characteristics of both 21 chromosomes of the father, it was concluded that its formation involved centric breakage and loss of centromeric material. The cell line with the 21q- chromosome may have originated from the translocation by an asymmetric misdivision of the reduced centromeric material. Of the two telocentrics produced by this fracture, one, possessing the smaller amount of centromeric apparatus, would be immediately lost; the other would be retained, but complete activity of its centromere would not be restored. It would therefore be unstable and might be lost.", "contents": "Unstable telocentric chromosome produced after centric misdivision of a 21q/21q translocated element. An unstable telocentric chromosome was found in an individual with Down's syndrome and an unusual chromosomal mosaic, 46,XX, t(21q21q)+,21-/46,XX,21q-/45,XX,21-. As the 21q/21q chromosome was of paternal origin, based on the characteristics of its centromeric heterochromatin and on the characteristics of both 21 chromosomes of the father, it was concluded that its formation involved centric breakage and loss of centromeric material. The cell line with the 21q- chromosome may have originated from the translocation by an asymmetric misdivision of the reduced centromeric material. Of the two telocentrics produced by this fracture, one, possessing the smaller amount of centromeric apparatus, would be immediately lost; the other would be retained, but complete activity of its centromere would not be restored. It would therefore be unstable and might be lost."} {"id": "PMID:153892", "title": "Effect of corn and sorghum diets in N1 methylnicotinamide excretion and hepatic enzymes in rats.", "content": "This study was carried out to compare the effects of corn (Zea mays) and sorghum (Sorghum vulgare) diets on urinary N1 methylnicotinamide (N'MN) excretion and on the activity of hepatic enzyme in young adult rats. Thirty rats, weighing an average of 174.3 g at the beginning of the experiments, were divided into three groups and studied for 13 weeks. The two experimental diets supplied 7% protein, and a casein diet was used as control. Niacin was excluded from the vitamin mixture used in the corn and sorghum diets. The activities of the following enzymes were studied: betaHOB-D, G6P-D, NADH2-TR, NADPH2-TR, and 3 HOA-0. Urinary excretion of N'MN was statistically different among the three groups, the corn group having the lowest level. The corn-fed animals appeared to have more obvious alterations in liver enzyme activity. The changes found in corn and sorghum-fed animals are different and cannot be explained as due to niacin deficiency. The different amino acid compositions of the two grains and their relationship with the discrepancies in the result are also discussed.", "contents": "Effect of corn and sorghum diets in N1 methylnicotinamide excretion and hepatic enzymes in rats. This study was carried out to compare the effects of corn (Zea mays) and sorghum (Sorghum vulgare) diets on urinary N1 methylnicotinamide (N'MN) excretion and on the activity of hepatic enzyme in young adult rats. Thirty rats, weighing an average of 174.3 g at the beginning of the experiments, were divided into three groups and studied for 13 weeks. The two experimental diets supplied 7% protein, and a casein diet was used as control. Niacin was excluded from the vitamin mixture used in the corn and sorghum diets. The activities of the following enzymes were studied: betaHOB-D, G6P-D, NADH2-TR, NADPH2-TR, and 3 HOA-0. Urinary excretion of N'MN was statistically different among the three groups, the corn group having the lowest level. The corn-fed animals appeared to have more obvious alterations in liver enzyme activity. The changes found in corn and sorghum-fed animals are different and cannot be explained as due to niacin deficiency. The different amino acid compositions of the two grains and their relationship with the discrepancies in the result are also discussed."} {"id": "PMID:153893", "title": "Improvement in the fertility of streptozotocin-diabetic male rats following treatment with insulin and human chrionic gonadotropin.", "content": "Diabetes was produced in male rats with streptozotocin. Some of them were subsequently treated with exogenous insulin, human chorionic gonadotropin (hCG) or both. The rats were tested six weeks later for fertility, testosterone secretion and spermatogenesis. Diabetes was found to inhibit all three parameters of fertility. Accessory gland atrophy was restodred following the treatment with insulin and much improved with insulin plus hCG. In a diabetic control group on restricted food intake, insulin alone did not significantly improve fertility, whereas hCG enhanced steroidegenesis and spermatogenesis but not fertility. Treatment with both hCG and sinulsin gave the best results.", "contents": "Improvement in the fertility of streptozotocin-diabetic male rats following treatment with insulin and human chrionic gonadotropin. Diabetes was produced in male rats with streptozotocin. Some of them were subsequently treated with exogenous insulin, human chorionic gonadotropin (hCG) or both. The rats were tested six weeks later for fertility, testosterone secretion and spermatogenesis. Diabetes was found to inhibit all three parameters of fertility. Accessory gland atrophy was restodred following the treatment with insulin and much improved with insulin plus hCG. In a diabetic control group on restricted food intake, insulin alone did not significantly improve fertility, whereas hCG enhanced steroidegenesis and spermatogenesis but not fertility. Treatment with both hCG and sinulsin gave the best results."} {"id": "PMID:153894", "title": "Selective excitation of mithramycin or DAPI fluorescence on double-stained cell nuclei and chromosomes.", "content": "Fluorescence spectra of leukocytes stained by both mithramycin and DAPI showed that the fluorescence of the two dyes can be separated efficiently by using different excitation wavelengths, for instance the 435 nm and the 365 nm mercury lines. In human chromosomes the complementary (\"reverse\") banding pattern produced by these dyes may thus be observed on double stained chromosome spreads. In plants, for instance in Anemone blanda, the two dyes may reveal two different banding patterns. The results of absorption and fluorescence measurements suggest the existence of at least two binding sites, or types, for each dye, with different fluorescent yields and binding strengths.", "contents": "Selective excitation of mithramycin or DAPI fluorescence on double-stained cell nuclei and chromosomes. Fluorescence spectra of leukocytes stained by both mithramycin and DAPI showed that the fluorescence of the two dyes can be separated efficiently by using different excitation wavelengths, for instance the 435 nm and the 365 nm mercury lines. In human chromosomes the complementary (\"reverse\") banding pattern produced by these dyes may thus be observed on double stained chromosome spreads. In plants, for instance in Anemone blanda, the two dyes may reveal two different banding patterns. The results of absorption and fluorescence measurements suggest the existence of at least two binding sites, or types, for each dye, with different fluorescent yields and binding strengths."} {"id": "PMID:153895", "title": "The localization of enzyme activities in the pancreatic appendages of Sepia officinalis L. (Cephalopoda).", "content": "In this study, enzyme activities of the pancreatic appendages of the ductus hepatoPancreas (the so-called \"pancreas\") in Sepia officinalis L. have been demonstrated by light and electron micicroscopical methods: Malate dehydrogenase, monoamine oxidase, acid phosphatase, beta-glucuronidase, adenosine triphosphatase and carbonic anhydrase were shown by the former, and monoamine oxidase, catalase, glutamic oxalacetic transaminase, choline esterase (non-specific), alkaline phosphatase, acid phosphatase and carbonic anhydrase by the latter technique. The correlation between enzyme activity and distribution, and the presumed function of the two pancreatic epithelia is discussed.", "contents": "The localization of enzyme activities in the pancreatic appendages of Sepia officinalis L. (Cephalopoda). In this study, enzyme activities of the pancreatic appendages of the ductus hepatoPancreas (the so-called \"pancreas\") in Sepia officinalis L. have been demonstrated by light and electron micicroscopical methods: Malate dehydrogenase, monoamine oxidase, acid phosphatase, beta-glucuronidase, adenosine triphosphatase and carbonic anhydrase were shown by the former, and monoamine oxidase, catalase, glutamic oxalacetic transaminase, choline esterase (non-specific), alkaline phosphatase, acid phosphatase and carbonic anhydrase by the latter technique. The correlation between enzyme activity and distribution, and the presumed function of the two pancreatic epithelia is discussed."} {"id": "PMID:153896", "title": "Laparoscopy in zoological medicine.", "content": "The technique of laparoscopy was adapted and utilized in zoological medicine for various mammals, birds, and reptiles for reproductive and diagnostic studies as well as clinically related research. It was concluded that since anesthesia was routinely required for most manipulative procedures in zoo animals, and since laparoscopy adds little additional risk, the use of this technique provides an additional diagnostic aid when indicated. Laparoscopy was found to be effective for evaluating reproductive status, particularly ovarian anatomy and function, direct visual biopsy of internal organs, sex determination in selected birds, and as a surgical means of fertility control.", "contents": "Laparoscopy in zoological medicine. The technique of laparoscopy was adapted and utilized in zoological medicine for various mammals, birds, and reptiles for reproductive and diagnostic studies as well as clinically related research. It was concluded that since anesthesia was routinely required for most manipulative procedures in zoo animals, and since laparoscopy adds little additional risk, the use of this technique provides an additional diagnostic aid when indicated. Laparoscopy was found to be effective for evaluating reproductive status, particularly ovarian anatomy and function, direct visual biopsy of internal organs, sex determination in selected birds, and as a surgical means of fertility control."} {"id": "PMID:153897", "title": "Requirement for membrane potential in active transport of glutamine by Escherichia coli.", "content": "The effect of reducing the membrane potential on glutamine transport in cells of Escherichia coli has been investigated. Addition of valinomycin to tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetic acid-treated E. coli cells in the presence of 20 mM exogenous potassium reduced the membrane potential, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium, and caused a complete inhibition of glutamine transport. Valinomycin plus potassium also caused a rapid decrease in the intracellular levels of ATP of normal E. coli cells, but had little if any effect on the ATP levels of two mutants of E. coli carrying lesions in the energy-transducing ATP complex (unc mutants). Yet both the membrane potential and the capacity to transport glutamine were depressed in the unc mutants by valinomycin and potassium. These findings are consistent with the hypothesis that both ATP and a membrane potential are essential to the active transport of glutamine by E. coli cells.", "contents": "Requirement for membrane potential in active transport of glutamine by Escherichia coli. The effect of reducing the membrane potential on glutamine transport in cells of Escherichia coli has been investigated. Addition of valinomycin to tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetic acid-treated E. coli cells in the presence of 20 mM exogenous potassium reduced the membrane potential, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium, and caused a complete inhibition of glutamine transport. Valinomycin plus potassium also caused a rapid decrease in the intracellular levels of ATP of normal E. coli cells, but had little if any effect on the ATP levels of two mutants of E. coli carrying lesions in the energy-transducing ATP complex (unc mutants). Yet both the membrane potential and the capacity to transport glutamine were depressed in the unc mutants by valinomycin and potassium. These findings are consistent with the hypothesis that both ATP and a membrane potential are essential to the active transport of glutamine by E. coli cells."} {"id": "PMID:153898", "title": "Nature of 6-methylpurine inhibition and characterization of two 6-methylpurine-resistant mutants of Neurospora crassa.", "content": "6-Methylpurine, an analog of adenine, inhibits the growth of Neurospora crassa. From kinetic studies it was found that 6-methylpurine is converted to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7), and inhibits the de novo purine biosynthesis. Adenine relieves the growth inhibition caused by 6-methylpurine, whereas hypoxanthine is not very effective. Studies dealing with hypoxanthine utilization in the presence of 6-methylpurine indicated a severely reduced uptake of hypoxanthine and a general slowdown in its further metabolism. Two mutants (Mepr-3 and Mepr-10) which are resistant to 6-methylpurine were characterized. Studies of purine base uptake and the in vivo and in vitro conversion to nucleotides indicated that Mepr-10 may be an adenine phosphoribosyltransferase-defective mutant, whereas Mepr-3 may be a mutant with altered feedback response to 6-methylpurine. Both mutants showed a severely lowered hypoxanthine phosphoribosyltransferase activity, but because 6-methylpurine did not have any effect on the conversion of hypoxanthine to IMP in the wild type, it was concluded that 6-methylpurine resistance in these mutants cannot be due to lowered hypoxanthine phosphoribosyltransferase activity, but rather that the lowering of enzyme activity may be a secondary effect.", "contents": "Nature of 6-methylpurine inhibition and characterization of two 6-methylpurine-resistant mutants of Neurospora crassa. 6-Methylpurine, an analog of adenine, inhibits the growth of Neurospora crassa. From kinetic studies it was found that 6-methylpurine is converted to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7), and inhibits the de novo purine biosynthesis. Adenine relieves the growth inhibition caused by 6-methylpurine, whereas hypoxanthine is not very effective. Studies dealing with hypoxanthine utilization in the presence of 6-methylpurine indicated a severely reduced uptake of hypoxanthine and a general slowdown in its further metabolism. Two mutants (Mepr-3 and Mepr-10) which are resistant to 6-methylpurine were characterized. Studies of purine base uptake and the in vivo and in vitro conversion to nucleotides indicated that Mepr-10 may be an adenine phosphoribosyltransferase-defective mutant, whereas Mepr-3 may be a mutant with altered feedback response to 6-methylpurine. Both mutants showed a severely lowered hypoxanthine phosphoribosyltransferase activity, but because 6-methylpurine did not have any effect on the conversion of hypoxanthine to IMP in the wild type, it was concluded that 6-methylpurine resistance in these mutants cannot be due to lowered hypoxanthine phosphoribosyltransferase activity, but rather that the lowering of enzyme activity may be a secondary effect."} {"id": "PMID:153899", "title": "Genetic and physiological studies on the relationship between colicin B resistance and ferrienterochelin uptake in Escherichia coli K-12.", "content": "The Escherichia coli gene for the ferrienterochelin uptake and colicins B and D receptor protein is located at approximately 13 min, adjacent to or among genes for enterochelin biosynthetic enzymes. The two receptor functions (colicin and siderophore) are separable by mutation.", "contents": "Genetic and physiological studies on the relationship between colicin B resistance and ferrienterochelin uptake in Escherichia coli K-12. The Escherichia coli gene for the ferrienterochelin uptake and colicins B and D receptor protein is located at approximately 13 min, adjacent to or among genes for enterochelin biosynthetic enzymes. The two receptor functions (colicin and siderophore) are separable by mutation."} {"id": "PMID:153900", "title": "Binding of 30s dynein with the B-tubule of the outer doublet of axonemes from Tetrahymena pyriformis and adenosine triphosphate-induced dissociation of the complex.", "content": "The binding properties of dynein arms to the A- and B-tubules of outer doublets of cilia from Tetrahymena pyriformis were examined, with the following results: 1. When 30s dynein purified from Tetrahymena cilia was added to doublets deficient in dynein arms, it bound to both A- and B-tubules almost equally and formed arms along the edges. The overall length of arms bound to the A-tubule was 22 +/- 3 nm, and that of arms bound to the B-tubule was 24 +/- 3 nm. Each arm bound to the A- and B-tubules was pointed toward the base at angles of 55 degrees +/- 7 degrees and 48 degrees +/- 7 degrees, respectively. In the presence of sufficient amounts of dynein, the arms along the A- and B-tubules were located at intervals of 22.8 +/- 1.5 nm and 22.5 +/- 1.7 nm, respectively. 2. On adding ATP, only the arms bound to the B-tubule were dissociated from the doublet decorated with arms on both sides. The dissociated arms rebound themselves to the B-tubule after hydrolysis of the ATP. When several doublets decorated with arms along both A- and B-tubules were arrayed side by side, the interdoublet spacing increased from 14 +/- 2 nm to 17 +/- 2 nm on addition of ATP. 3. The turbidity of a suspension of trypsin [EC 3.4.21.4]-treated axonemes decreased rapidly on addition of ATP, then recovered partially. Observations by dark-field microscopy and electron microscopy showed that the doublets which had slid out from the axonemes on ATP addition formed large aggregates after hydrolysis of the ATP. The dynein arms were also solubilized from the axonemes upon addition of ATP, and rebound themselves to the B-tubule after hydrolysis of the added ATP. 4. The double-reciprocal plot for the ATPase [EC 3.6.1.3] activity of the trypsin-treated axonemes against ATP concentration was composed of two straight lines, from which the Km values were estimated to be 1.0 and 12.7 micrometer. The dependence of the decrease in turbidity of the axonemal suspension on ATP concentration indicated that the binding of ATP to sites with an apparent dissociation constant of 1 micrometer induced dissociation of the arms from the B-tubule.", "contents": "Binding of 30s dynein with the B-tubule of the outer doublet of axonemes from Tetrahymena pyriformis and adenosine triphosphate-induced dissociation of the complex. The binding properties of dynein arms to the A- and B-tubules of outer doublets of cilia from Tetrahymena pyriformis were examined, with the following results: 1. When 30s dynein purified from Tetrahymena cilia was added to doublets deficient in dynein arms, it bound to both A- and B-tubules almost equally and formed arms along the edges. The overall length of arms bound to the A-tubule was 22 +/- 3 nm, and that of arms bound to the B-tubule was 24 +/- 3 nm. Each arm bound to the A- and B-tubules was pointed toward the base at angles of 55 degrees +/- 7 degrees and 48 degrees +/- 7 degrees, respectively. In the presence of sufficient amounts of dynein, the arms along the A- and B-tubules were located at intervals of 22.8 +/- 1.5 nm and 22.5 +/- 1.7 nm, respectively. 2. On adding ATP, only the arms bound to the B-tubule were dissociated from the doublet decorated with arms on both sides. The dissociated arms rebound themselves to the B-tubule after hydrolysis of the ATP. When several doublets decorated with arms along both A- and B-tubules were arrayed side by side, the interdoublet spacing increased from 14 +/- 2 nm to 17 +/- 2 nm on addition of ATP. 3. The turbidity of a suspension of trypsin [EC 3.4.21.4]-treated axonemes decreased rapidly on addition of ATP, then recovered partially. Observations by dark-field microscopy and electron microscopy showed that the doublets which had slid out from the axonemes on ATP addition formed large aggregates after hydrolysis of the ATP. The dynein arms were also solubilized from the axonemes upon addition of ATP, and rebound themselves to the B-tubule after hydrolysis of the added ATP. 4. The double-reciprocal plot for the ATPase [EC 3.6.1.3] activity of the trypsin-treated axonemes against ATP concentration was composed of two straight lines, from which the Km values were estimated to be 1.0 and 12.7 micrometer. The dependence of the decrease in turbidity of the axonemal suspension on ATP concentration indicated that the binding of ATP to sites with an apparent dissociation constant of 1 micrometer induced dissociation of the arms from the B-tubule."} {"id": "PMID:153901", "title": "Biosynthesis of glycogen in Neurospora crassa. Kinetic mechanism of UDP-glucose: glycogen 4-alpha-glucosyltransferase.", "content": "The kinetic mechanism of glycogen synthase [UDP-glucose: glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11], glucose-6-P-dependent form, from Neurospora crassa has been investigated by initial velocity experiments and studies with inhibitors in the presence of sufficient levels of glucose-6-P. The rate equation was different from those of common two-substrate systems because one of the substrates, glycogen, is also a product. The reaction rates were determined by varying the concentration of one of the substrates while keeping that of the other constant. Double-reciprocal plots of initial velocity measurements were linear and showed converging line patterns. UDP was found to act competitively when the substrate UDP-glucose was varied, but noncompetitively when glycogen was varied. On the basis of these results, it is concluded that glycogen synthase, glucose-6-P-dependent form, from N. crassa has a rapid equilibrium random Bi-Bi mechanism. Rate constant and dissociation constants for each step of this mechanism were estimated.", "contents": "Biosynthesis of glycogen in Neurospora crassa. Kinetic mechanism of UDP-glucose: glycogen 4-alpha-glucosyltransferase. The kinetic mechanism of glycogen synthase [UDP-glucose: glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11], glucose-6-P-dependent form, from Neurospora crassa has been investigated by initial velocity experiments and studies with inhibitors in the presence of sufficient levels of glucose-6-P. The rate equation was different from those of common two-substrate systems because one of the substrates, glycogen, is also a product. The reaction rates were determined by varying the concentration of one of the substrates while keeping that of the other constant. Double-reciprocal plots of initial velocity measurements were linear and showed converging line patterns. UDP was found to act competitively when the substrate UDP-glucose was varied, but noncompetitively when glycogen was varied. On the basis of these results, it is concluded that glycogen synthase, glucose-6-P-dependent form, from N. crassa has a rapid equilibrium random Bi-Bi mechanism. Rate constant and dissociation constants for each step of this mechanism were estimated."} {"id": "PMID:153902", "title": "Two calcium regulation systems in squid (Ommastrephes sloani pacificus) muscle. Preparation of calcium-sensitive myosin and troponin-tropomyosin.", "content": "The Ca-regulatory system in squid mantle muscle was studied. The findings were as follows. (a) Squid mantle myosin B (squid myosin B) was Ca-sensitive, and its Ca-sensitivity was unaffected by addition of a large amount of rabbit skeletal myosin (skeletal myosin) or rabbit skeletal F-actin (skeletal F-actin). (b) Squid myosin was prepared from the mantle muscle. It showed a heavy chain component and two light chain components in the SDS-gel electrophoretic pattern: the molecular weights of the latter two were 17,000 and 15,000. Actomyosin reconstituted from squid myosin and skeletal (or squid) actin showed Ca-sensitivity in superprecipitation and Mg-ATPase assays. EDTA- treatment had no effect on the Ca-sensitivity of squid myosin. (c) Squid mantle actin (squid actin) was prepared by the method of Spudich and Watt. Hybrid actomyosin reconstituted by using the pure squid actin preparation with skeletal myosin showed no Ca-sensitivity in Mg-ATPase assay, whereas that reconstituted using crude squid actin showed marked Ca-sensitivity. The crude squid actin contained four protein components which were capable of associating with F-actin in 0.1 M KCl, 1 mM MgCl2 and 20 mM Tris-maleate (pH7.5). (d) Native tropomyosin was prepared from squid mantle muscle, and it conferred Ca-sensitivity on skeletal actomyosin as well as on a hybrid actomyosin reconstituted from squid actin and skeletal myosin. (e) Squid native tropomyosin was separated into troponin and tropomyosin fractions by placing it in 0.4 M LiCl at pH 4.7. The troponin fraction was further purified by DEAE-cellulose chromatography. Squid troponin thus obtained was different in mobility from rabbit skeletal or carp dorsal troponin; three bands of squid troponin corresponded to molecular weights of 52,000, 28,000, and 24,000 daltons. It could confer Ca-sensitivity in the presence of tropomyosin on skeletal actomyosin as well as on a hybrid reconstituted from squid actin and skeletal myosin. (f) Squid myosin B, and two hybrid actomyosins were compared as regards Ca and Sr requirements for their Mg-ATPase activities. The myosin-linked regulatory system rather than the thin-filament-linked regulatory system was predominant in squid myosin B. Squid myosin B required higher Ca2+ and Sr2+ concentrations for Mg-ATPase activity; half-maximal activation of Mg-ATPase was obtained at 0.8 micron Ca2+ and 28 micron Sr2+ with skeletal myosin B, and at 2.5 micron Ca2+ and 140 micron Sr2+ with squid myosin B.", "contents": "Two calcium regulation systems in squid (Ommastrephes sloani pacificus) muscle. Preparation of calcium-sensitive myosin and troponin-tropomyosin. The Ca-regulatory system in squid mantle muscle was studied. The findings were as follows. (a) Squid mantle myosin B (squid myosin B) was Ca-sensitive, and its Ca-sensitivity was unaffected by addition of a large amount of rabbit skeletal myosin (skeletal myosin) or rabbit skeletal F-actin (skeletal F-actin). (b) Squid myosin was prepared from the mantle muscle. It showed a heavy chain component and two light chain components in the SDS-gel electrophoretic pattern: the molecular weights of the latter two were 17,000 and 15,000. Actomyosin reconstituted from squid myosin and skeletal (or squid) actin showed Ca-sensitivity in superprecipitation and Mg-ATPase assays. EDTA- treatment had no effect on the Ca-sensitivity of squid myosin. (c) Squid mantle actin (squid actin) was prepared by the method of Spudich and Watt. Hybrid actomyosin reconstituted by using the pure squid actin preparation with skeletal myosin showed no Ca-sensitivity in Mg-ATPase assay, whereas that reconstituted using crude squid actin showed marked Ca-sensitivity. The crude squid actin contained four protein components which were capable of associating with F-actin in 0.1 M KCl, 1 mM MgCl2 and 20 mM Tris-maleate (pH7.5). (d) Native tropomyosin was prepared from squid mantle muscle, and it conferred Ca-sensitivity on skeletal actomyosin as well as on a hybrid actomyosin reconstituted from squid actin and skeletal myosin. (e) Squid native tropomyosin was separated into troponin and tropomyosin fractions by placing it in 0.4 M LiCl at pH 4.7. The troponin fraction was further purified by DEAE-cellulose chromatography. Squid troponin thus obtained was different in mobility from rabbit skeletal or carp dorsal troponin; three bands of squid troponin corresponded to molecular weights of 52,000, 28,000, and 24,000 daltons. It could confer Ca-sensitivity in the presence of tropomyosin on skeletal actomyosin as well as on a hybrid reconstituted from squid actin and skeletal myosin. (f) Squid myosin B, and two hybrid actomyosins were compared as regards Ca and Sr requirements for their Mg-ATPase activities. The myosin-linked regulatory system rather than the thin-filament-linked regulatory system was predominant in squid myosin B. Squid myosin B required higher Ca2+ and Sr2+ concentrations for Mg-ATPase activity; half-maximal activation of Mg-ATPase was obtained at 0.8 micron Ca2+ and 28 micron Sr2+ with skeletal myosin B, and at 2.5 micron Ca2+ and 140 micron Sr2+ with squid myosin B."} {"id": "PMID:153903", "title": "Myosin and actin from Escherichia coli K12 C600.", "content": "Myosin-like protein and actin-like protein from E. coli formed filaments very similar in structure to those of myosin and actin from skeletal muscle. At 0.2 M KCl, a large number of \"thick filaments\" of uniform size (about 0.6-0.7 micron long and about 20 nm wide) was present. These thick filaments aggregated as the KCl concentration decreased to less than 0.2 M. Filaments of actin-like protein were decorated with muscle heavy meromyosin, showing \"arrowheads\". The arrowhead structure disappeared in the presence of ATP. A mixture of E. coli myosin-like protein and rabbit skeletal actin exhibited a gelation phenomenon on the additon of ATP. The phenomenon was reversible and showed ATP specificity. However, the gelation phenomenon was not observed with the mixture of E. coli actin-like protein and E. coli myosin-like protein. These results provide compelling evidence that the E. coli myosin-like protein and actin-like protein we isolated are essentially identical to myosin and actin, respectively.", "contents": "Myosin and actin from Escherichia coli K12 C600. Myosin-like protein and actin-like protein from E. coli formed filaments very similar in structure to those of myosin and actin from skeletal muscle. At 0.2 M KCl, a large number of \"thick filaments\" of uniform size (about 0.6-0.7 micron long and about 20 nm wide) was present. These thick filaments aggregated as the KCl concentration decreased to less than 0.2 M. Filaments of actin-like protein were decorated with muscle heavy meromyosin, showing \"arrowheads\". The arrowhead structure disappeared in the presence of ATP. A mixture of E. coli myosin-like protein and rabbit skeletal actin exhibited a gelation phenomenon on the additon of ATP. The phenomenon was reversible and showed ATP specificity. However, the gelation phenomenon was not observed with the mixture of E. coli actin-like protein and E. coli myosin-like protein. These results provide compelling evidence that the E. coli myosin-like protein and actin-like protein we isolated are essentially identical to myosin and actin, respectively."} {"id": "PMID:153904", "title": "Coupling factor ATPase from Escherichia coli. An uncA mutant (uncA401) with defective alpha subunit.", "content": "Inactive coupling factor ATPase (F1) was prepared from an uncoupled mutant (uncA401) of Escherichia coli. Reconstitution of ATPase activity was observed when alpha subunit from wild-type F1 was added to the dissociated inactive F1 and the mixture was dialyzed against buffer containing ATP and Mg2+. ATPase was also reconstituted when the mixture of alpha subunit (wild type) and crude extract from the mutant was dialyzed against the same buffer. These results indicate that the mutant is defective in alpha subunit, suggesting that the uncA401 locus carries the structural gene for alpha subunit, and that this polypeptide plays an essential role in ATPase activity in F1 molecule.", "contents": "Coupling factor ATPase from Escherichia coli. An uncA mutant (uncA401) with defective alpha subunit. Inactive coupling factor ATPase (F1) was prepared from an uncoupled mutant (uncA401) of Escherichia coli. Reconstitution of ATPase activity was observed when alpha subunit from wild-type F1 was added to the dissociated inactive F1 and the mixture was dialyzed against buffer containing ATP and Mg2+. ATPase was also reconstituted when the mixture of alpha subunit (wild type) and crude extract from the mutant was dialyzed against the same buffer. These results indicate that the mutant is defective in alpha subunit, suggesting that the uncA401 locus carries the structural gene for alpha subunit, and that this polypeptide plays an essential role in ATPase activity in F1 molecule."} {"id": "PMID:153905", "title": "Structure and function of chicken gizzard myosin.", "content": "In our previous study (Onishi, H., Susuki, H., Nakamura, k., and Watanabe, S. J. Biochem. 83, 835-847, 1978), we found it to be characteristic of chicken gizzard myosin that thick filaments of gizzard myosin are readily disassembled by a stoichiometric amount of ATP (3 mol of ATP per mol of myosin), and that the ATPase activity of gizzard myosin in the ATP-disassembled state is much lower than that of gizzard myosin disassembled by a high concentration of KCl. We now report the following findings: (1) Thick filaments of (unphosphorylated) gizzard myosin can be in a bipolar structure or in a non-polar structure, depending on the method of preparing the thick filaments. (2) Thick filaments of (unphosphorylated) gizzard myosin in either the bioplar or the non-polar structure are readily disassembled by ATP. (3) Addition of rabbit skeletal C-protein does not confer ATP resistance on thick filaments of (unphosphorylated) gizzard myosin. (4) Unphosphorylated) gizzard myosin in the ATP-disassembled state is in a dimeric form as determined by ultracentrifugation. Moreover, 0.2 M KCl-dissociated gizzard myosin in monomeric form is converted to a dimeric form by ATP. (5) The Mg-ATPase activity of (unphosphorylated) gizzard myosin is much lower in its dimeric form (less than one-tenth) than in its monomeric form. The activity depression observed around 0.15 M KCl is therefore due to the formation of myosin dimers. (6) Skeletal L-meromyosin can increase the very low activity of (unphosphorylated) gizzard myosin ATPase at low ionic strength (0.13 M KCl) by forming ATP-resistant hybrid filaments with (unphosphorylated) gizzard myosin, preventing the formation of myosin dimers. (7) Gizzard myosin in which one of the light-chain components is phosphorylated by myosin light-chain kinase can form thick filaments which are resistant to the disassembling action of ATP. (8) Even in the presence of ATP, thick filaments of phosphorylated gizzard myosin do not disassembled into myosin dimers. Accordingly, the ATPase activity of phosphorylated gizzard myosin does not show activity depression at low ionic strength.", "contents": "Structure and function of chicken gizzard myosin. In our previous study (Onishi, H., Susuki, H., Nakamura, k., and Watanabe, S. J. Biochem. 83, 835-847, 1978), we found it to be characteristic of chicken gizzard myosin that thick filaments of gizzard myosin are readily disassembled by a stoichiometric amount of ATP (3 mol of ATP per mol of myosin), and that the ATPase activity of gizzard myosin in the ATP-disassembled state is much lower than that of gizzard myosin disassembled by a high concentration of KCl. We now report the following findings: (1) Thick filaments of (unphosphorylated) gizzard myosin can be in a bipolar structure or in a non-polar structure, depending on the method of preparing the thick filaments. (2) Thick filaments of (unphosphorylated) gizzard myosin in either the bioplar or the non-polar structure are readily disassembled by ATP. (3) Addition of rabbit skeletal C-protein does not confer ATP resistance on thick filaments of (unphosphorylated) gizzard myosin. (4) Unphosphorylated) gizzard myosin in the ATP-disassembled state is in a dimeric form as determined by ultracentrifugation. Moreover, 0.2 M KCl-dissociated gizzard myosin in monomeric form is converted to a dimeric form by ATP. (5) The Mg-ATPase activity of (unphosphorylated) gizzard myosin is much lower in its dimeric form (less than one-tenth) than in its monomeric form. The activity depression observed around 0.15 M KCl is therefore due to the formation of myosin dimers. (6) Skeletal L-meromyosin can increase the very low activity of (unphosphorylated) gizzard myosin ATPase at low ionic strength (0.13 M KCl) by forming ATP-resistant hybrid filaments with (unphosphorylated) gizzard myosin, preventing the formation of myosin dimers. (7) Gizzard myosin in which one of the light-chain components is phosphorylated by myosin light-chain kinase can form thick filaments which are resistant to the disassembling action of ATP. (8) Even in the presence of ATP, thick filaments of phosphorylated gizzard myosin do not disassembled into myosin dimers. Accordingly, the ATPase activity of phosphorylated gizzard myosin does not show activity depression at low ionic strength."} {"id": "PMID:153909", "title": "Odontoblast alkaline phosphatases and Ca2+ transport.", "content": "The same isoenzyme of nonspecific alkaline phosphatase (APase), assayed with p-nitrophenylphosphate (p-NPP), was shown be present in different calcifying tissues, bone, calcifying cartilage, odontoblasts and enamel organ. Indications were also found that the enzymatic degradation of inorganic pyrophosphate (PPi) in calcifying tissues is mediated by APase. By using specific APase inhibitors, it was shown that two enzymes capable of degrading ATP exist. These were characterized in dentinogenically active odontoblasts, and it was concluded that one is the classical APase, the other is a Ca2+ and Mg2+ activated ATPase, named Ca2+-ATPase. The two phosphatases were solubilized from odontoblasts and separated. The localization of APase and Ca2+-ATPase in odontoblasts was investigated by subcellular fractionation and EM histochemistry. Routine methods for fixation were found to almost completely inactivate the enzymes. By using a mild fixation technique that preserved 80% of the enzyme activity, the main localization for both APase and Ca2+-ATPase was found to be in the membranes of intercellular vesicles located in the cell body and odontoblasts process. No activity was found in the cell membranes. It is concluded that there are at least two enzymes able to degrade phosphate compounds at alkaline pH in hard tissue forming cells. One is the nonspecific alkaline phosphatase (APase; EC 3. 1. 3. 1), which is active against p-NPP, PPi, glycerophosphates and ATP among other substrates. The other is a more specific Ca2+-ATPase (EC 3. 6. 1. 3). There seems to be an intimate relation between these two enzymes in the tissue. The function of APase in biological calcification is still obscure. In contrast, the finding of an ATP dependent, intravesicularly directed, transmembranous Ca2+-transport in vesicles derived from the microsomal fraction of odontoblasts may explain the role of Ca2+-ATPase.", "contents": "Odontoblast alkaline phosphatases and Ca2+ transport. The same isoenzyme of nonspecific alkaline phosphatase (APase), assayed with p-nitrophenylphosphate (p-NPP), was shown be present in different calcifying tissues, bone, calcifying cartilage, odontoblasts and enamel organ. Indications were also found that the enzymatic degradation of inorganic pyrophosphate (PPi) in calcifying tissues is mediated by APase. By using specific APase inhibitors, it was shown that two enzymes capable of degrading ATP exist. These were characterized in dentinogenically active odontoblasts, and it was concluded that one is the classical APase, the other is a Ca2+ and Mg2+ activated ATPase, named Ca2+-ATPase. The two phosphatases were solubilized from odontoblasts and separated. The localization of APase and Ca2+-ATPase in odontoblasts was investigated by subcellular fractionation and EM histochemistry. Routine methods for fixation were found to almost completely inactivate the enzymes. By using a mild fixation technique that preserved 80% of the enzyme activity, the main localization for both APase and Ca2+-ATPase was found to be in the membranes of intercellular vesicles located in the cell body and odontoblasts process. No activity was found in the cell membranes. It is concluded that there are at least two enzymes able to degrade phosphate compounds at alkaline pH in hard tissue forming cells. One is the nonspecific alkaline phosphatase (APase; EC 3. 1. 3. 1), which is active against p-NPP, PPi, glycerophosphates and ATP among other substrates. The other is a more specific Ca2+-ATPase (EC 3. 6. 1. 3). There seems to be an intimate relation between these two enzymes in the tissue. The function of APase in biological calcification is still obscure. In contrast, the finding of an ATP dependent, intravesicularly directed, transmembranous Ca2+-transport in vesicles derived from the microsomal fraction of odontoblasts may explain the role of Ca2+-ATPase."} {"id": "PMID:153910", "title": "Occurrence and significance of oxygen exchange reactions catalyzed by mitochondrial adenosine triphosphatase preparations.", "content": "The capacity of various ATPase preparations from beef heart mitochondria to catalyze exchange of phosphate oxygens with water has been evaluated. Oligomycin-sensitive ATPase preparations retain a capacity for considerable intermediate Pi equilibrium HOH exchange per Pi formed during ATP hydrolysis at relatively high ATP concentration (5 mM). Submitochondrial particles prepared by an ammonia-Sephadex procedure with 5 mM ATP showed more rapid ATPase, less oligomycin sensitivity, and less capacity for intermediate exchange. With these particles, intermediate Pi equilibrium HOH exchange per Pi formed was increased as ATP concentration was decreased. The purified, soluble ATPase from mitochondria catalyzed little or no intermediate Pi equilibrium HOH exchange at 5 mM ATP but showed pronounced increase in capacity for such exchange as ATP concentration was lowered. The ATPase also showed a weak catalysis of an ADP-stimulated medium Pi equilibrium HOH exchange. The results support the alternating catalytic site model for ATP synthesis or cleavage. They also demonstrate that a transmembrane protonmotive force is not necessary for oxygen exchange reactions. At lower ATP concentrations, ADP and Pi formed at a catalytic site appear to remain bound and continue to allow exchange of Pi oxygens until ATP binds at another site on the enzyme.", "contents": "Occurrence and significance of oxygen exchange reactions catalyzed by mitochondrial adenosine triphosphatase preparations. The capacity of various ATPase preparations from beef heart mitochondria to catalyze exchange of phosphate oxygens with water has been evaluated. Oligomycin-sensitive ATPase preparations retain a capacity for considerable intermediate Pi equilibrium HOH exchange per Pi formed during ATP hydrolysis at relatively high ATP concentration (5 mM). Submitochondrial particles prepared by an ammonia-Sephadex procedure with 5 mM ATP showed more rapid ATPase, less oligomycin sensitivity, and less capacity for intermediate exchange. With these particles, intermediate Pi equilibrium HOH exchange per Pi formed was increased as ATP concentration was decreased. The purified, soluble ATPase from mitochondria catalyzed little or no intermediate Pi equilibrium HOH exchange at 5 mM ATP but showed pronounced increase in capacity for such exchange as ATP concentration was lowered. The ATPase also showed a weak catalysis of an ADP-stimulated medium Pi equilibrium HOH exchange. The results support the alternating catalytic site model for ATP synthesis or cleavage. They also demonstrate that a transmembrane protonmotive force is not necessary for oxygen exchange reactions. At lower ATP concentrations, ADP and Pi formed at a catalytic site appear to remain bound and continue to allow exchange of Pi oxygens until ATP binds at another site on the enzyme."} {"id": "PMID:153911", "title": "A nuclear mutation conferring aurovertin resistance to yeast mitochondrial adenosine triphosphatase.", "content": "A single gene nuclear yeast mutant was isolated whose mitochondrial F1-ATPase was resistant to the specific F1 inhibitor aurovertin. The mutant enzyme was not cross-resistant to other F1 inhibitors. The binding of aurovertin to F1 and to the two largest F1 subunits (alpha and beta) was measured by enhancement of aurovertin fluorescence. Aurovertin bound to wild type F1-ATPase and to its monomeric beta subunit with about the same binding constant. It failed to bind to wild type alpha subunit or to either F1 or F1 subunits from the mutant. The aurovertin-resistant mutant thus contains an altered nuclear gene which specifies the structure of the beta subunit of F1.", "contents": "A nuclear mutation conferring aurovertin resistance to yeast mitochondrial adenosine triphosphatase. A single gene nuclear yeast mutant was isolated whose mitochondrial F1-ATPase was resistant to the specific F1 inhibitor aurovertin. The mutant enzyme was not cross-resistant to other F1 inhibitors. The binding of aurovertin to F1 and to the two largest F1 subunits (alpha and beta) was measured by enhancement of aurovertin fluorescence. Aurovertin bound to wild type F1-ATPase and to its monomeric beta subunit with about the same binding constant. It failed to bind to wild type alpha subunit or to either F1 or F1 subunits from the mutant. The aurovertin-resistant mutant thus contains an altered nuclear gene which specifies the structure of the beta subunit of F1."} {"id": "PMID:153913", "title": "The cellular basis of the impaired autologous mixed lymphocyte reaction in patients with systemic lupus erythematosus.", "content": "The autologous mixed lymphocyte reaction is impaired in patients with systemic lupus erythematosus. This is because nonthymus-derived (T)-lymphocyte preparations from such patients do not stimulate autologous T-lymphocyte proliferation normally. This defect may explain the impaired generation of suppressor activity in systemic lupus erythematosus and thereby the occurrence of autoantibodies in this disease.", "contents": "The cellular basis of the impaired autologous mixed lymphocyte reaction in patients with systemic lupus erythematosus. The autologous mixed lymphocyte reaction is impaired in patients with systemic lupus erythematosus. This is because nonthymus-derived (T)-lymphocyte preparations from such patients do not stimulate autologous T-lymphocyte proliferation normally. This defect may explain the impaired generation of suppressor activity in systemic lupus erythematosus and thereby the occurrence of autoantibodies in this disease."} {"id": "PMID:153914", "title": "Mechanisms of lymphocyte activation: the role of suppressor cells in the proliferative responses of chronic lymphatic leukemia lymphocytes.", "content": "Binding of (125)I-leukoagglutinin (LPHA) to lymphocyte membrane receptors at equilibrium generated similar curvilinear Scatchard plots in 20 patients with bursa-derived (B)-cell-type chronic lymphatic leukemia (CLL) and 15 controls. If biphasic plots are assumed, the two linear components show markedly diminished receptor capacity (15 and 137 ng/10(6) lymphocytes) in CLL as compared to controls (60 and 668 ng). In contrast, affinity was similar in patients (1.0 x 10(8) M(-1) and 2.1 x 10(6) M(-1)) and controls (1.8 x 10(8) M(-1) and 1.5 x 10(6) M(-1)). Highly purified B cells from patients and controls generated binding data comparable to that obtained from the mixed lymphocyte (ML) suspensions from which they originated. Maximal DNA synthesis of highly purified, normal, thymus-derived (T) and B cells in response to LPHA stimulation was comparable to that of ML (mitotic index [MI] 19.9, 20.1, and 23.4, respectively), though B-cell responses were slightly delayed. In CLL the markedly decreased and delayed DNA synthesis by ML (MI 2.3), and by highly purified T (MI 1.6) and B (MI 1.9) cells seemed out of proportion to their decreased receptor capacity for LPHA. The impaired mitogenic responses of leukemic cells from five patients were not enhanced when cocultured with normal lymphocytes. In contrast, cells from eight patients inhibited cocultured normal lymphocyte responses to LPHA by 94.3%. Sera from these patients and supernates from their cultured cells did not mediate this suppressor effect. These observations indicate that the decreased DNA synthesis observed in CLL is not an attribute of B cells and does not represent the expected response of a few residual normal T lymphocytes, but rather reflects impaired responses by all CLL cells. The defect does not relate to the density or function of membrane receptors for LPHA, to the presence of inhibitors in these patients' sera, or to depletion of helper T cells. Our data strongly suggest that one mechanism for the immunoincompetence observed in CLL reflects excessive suppressor-cell activity.", "contents": "Mechanisms of lymphocyte activation: the role of suppressor cells in the proliferative responses of chronic lymphatic leukemia lymphocytes. Binding of (125)I-leukoagglutinin (LPHA) to lymphocyte membrane receptors at equilibrium generated similar curvilinear Scatchard plots in 20 patients with bursa-derived (B)-cell-type chronic lymphatic leukemia (CLL) and 15 controls. If biphasic plots are assumed, the two linear components show markedly diminished receptor capacity (15 and 137 ng/10(6) lymphocytes) in CLL as compared to controls (60 and 668 ng). In contrast, affinity was similar in patients (1.0 x 10(8) M(-1) and 2.1 x 10(6) M(-1)) and controls (1.8 x 10(8) M(-1) and 1.5 x 10(6) M(-1)). Highly purified B cells from patients and controls generated binding data comparable to that obtained from the mixed lymphocyte (ML) suspensions from which they originated. Maximal DNA synthesis of highly purified, normal, thymus-derived (T) and B cells in response to LPHA stimulation was comparable to that of ML (mitotic index [MI] 19.9, 20.1, and 23.4, respectively), though B-cell responses were slightly delayed. In CLL the markedly decreased and delayed DNA synthesis by ML (MI 2.3), and by highly purified T (MI 1.6) and B (MI 1.9) cells seemed out of proportion to their decreased receptor capacity for LPHA. The impaired mitogenic responses of leukemic cells from five patients were not enhanced when cocultured with normal lymphocytes. In contrast, cells from eight patients inhibited cocultured normal lymphocyte responses to LPHA by 94.3%. Sera from these patients and supernates from their cultured cells did not mediate this suppressor effect. These observations indicate that the decreased DNA synthesis observed in CLL is not an attribute of B cells and does not represent the expected response of a few residual normal T lymphocytes, but rather reflects impaired responses by all CLL cells. The defect does not relate to the density or function of membrane receptors for LPHA, to the presence of inhibitors in these patients' sera, or to depletion of helper T cells. Our data strongly suggest that one mechanism for the immunoincompetence observed in CLL reflects excessive suppressor-cell activity."} {"id": "PMID:153912", "title": "Results following closure of ostium secundum atrial septal defects.", "content": "In a series of 41 patients of ASD (ostium secundum type) corrected by surgery, a clinical, radiological, electrocardiographic and echocardiographic follow-up study was performed. Good clinical results were obtained but some abnormalities can persist postoperatively: RV enlargement, dysrhythmias and mitral valve dysfunction.", "contents": "Results following closure of ostium secundum atrial septal defects. In a series of 41 patients of ASD (ostium secundum type) corrected by surgery, a clinical, radiological, electrocardiographic and echocardiographic follow-up study was performed. Good clinical results were obtained but some abnormalities can persist postoperatively: RV enlargement, dysrhythmias and mitral valve dysfunction."} {"id": "PMID:153918", "title": "Effects of the interpolated vibratory stimulation on the interdental dimension discrimination in normal and joint defect subjects.", "content": "No significant differences in the interdental dimension discrimination (IDD) ability were found between normal and joint defect subjects. Furthermore, vibration onto the mandible gave similar effects on the nature of IDD in both subject groups. Thus, the muscle spindles of masticatory muscles may contribute to IDD, but temporomandibular receptors may not.", "contents": "Effects of the interpolated vibratory stimulation on the interdental dimension discrimination in normal and joint defect subjects. No significant differences in the interdental dimension discrimination (IDD) ability were found between normal and joint defect subjects. Furthermore, vibration onto the mandible gave similar effects on the nature of IDD in both subject groups. Thus, the muscle spindles of masticatory muscles may contribute to IDD, but temporomandibular receptors may not."} {"id": "PMID:153921", "title": "Attitudinal differences of faculty and students regarding the care of special (handicapped) patients in a dental school clinic.", "content": "Faculty and students were surveyed as to their attitudes regarding the management of the special patient. This survey was completed after such a program was in existence for three years. Recommendations were made to better realize the overall goals of the program, especially that of encouraging the treatment of the special patients in the general practice of dentistry.", "contents": "Attitudinal differences of faculty and students regarding the care of special (handicapped) patients in a dental school clinic. Faculty and students were surveyed as to their attitudes regarding the management of the special patient. This survey was completed after such a program was in existence for three years. Recommendations were made to better realize the overall goals of the program, especially that of encouraging the treatment of the special patients in the general practice of dentistry."} {"id": "PMID:153922", "title": "Eliminating office architectural barriers to dental care of the elderly and handicapped.", "content": "Methods by which the most common architectural barriers to dental care for the elderly and handicapped can be overcome are described. Some physiological and medical conditions that necessitate special provisions in location and design of the office management of patients have been described. The consequences of accessibility have been discussed and suggestions for management of elderly and handicapped patients are presented.", "contents": "Eliminating office architectural barriers to dental care of the elderly and handicapped. Methods by which the most common architectural barriers to dental care for the elderly and handicapped can be overcome are described. Some physiological and medical conditions that necessitate special provisions in location and design of the office management of patients have been described. The consequences of accessibility have been discussed and suggestions for management of elderly and handicapped patients are presented."} {"id": "PMID:153929", "title": "In vivo activity of a nonspecific T cell-replacing factor.", "content": "Nonspecific T cell-replacing factors prepared as supernatants from mixed lymphocyte cultures or concanavalin A-stimulated spleen cells are active in vivo iv injected into nude mice at least 3 days before antigen. The supernatants appear to act by enhancing the week IgM responses that occur in untreated nudes. Secondary responses and IgG antibody were not found.", "contents": "In vivo activity of a nonspecific T cell-replacing factor. Nonspecific T cell-replacing factors prepared as supernatants from mixed lymphocyte cultures or concanavalin A-stimulated spleen cells are active in vivo iv injected into nude mice at least 3 days before antigen. The supernatants appear to act by enhancing the week IgM responses that occur in untreated nudes. Secondary responses and IgG antibody were not found."} {"id": "PMID:153930", "title": "Langerhans cells trap tick salivary gland antigens in tick-resistant guinea pigs.", "content": "In the infested skin of tick-resistant guinea pigs, indirect immunofluorescence techniques have revealed that antigens from the ticks' salivary glands are associated with discrete dendritic cells in the epidermis. Evidence is presented to support the suggestion that these antigen-retaining cells are Langerhans cells.", "contents": "Langerhans cells trap tick salivary gland antigens in tick-resistant guinea pigs. In the infested skin of tick-resistant guinea pigs, indirect immunofluorescence techniques have revealed that antigens from the ticks' salivary glands are associated with discrete dendritic cells in the epidermis. Evidence is presented to support the suggestion that these antigen-retaining cells are Langerhans cells."} {"id": "PMID:153933", "title": "Differential cyclophosphamide sensitivity of precursor cells in allogeneic and H-2 restricted cytotoxic responses.", "content": "Spleen cells from cyclophosphamide-treated mice responded in vitro to allogeneic stimulator cells but not to TNP-coupled syngeneic spleen cells. Similarly, cells from female mice, primed in vivo with syngeneic male cells, could not respond in vitro to male spleen cell stimulation if the mice were pretreated with cyclophosphamide. These results suggest that the precursor cells for H-2-restricted cytotoxic responses belong to a different T-cell subpopulation than the precursor cells for allogeneic responses.", "contents": "Differential cyclophosphamide sensitivity of precursor cells in allogeneic and H-2 restricted cytotoxic responses. Spleen cells from cyclophosphamide-treated mice responded in vitro to allogeneic stimulator cells but not to TNP-coupled syngeneic spleen cells. Similarly, cells from female mice, primed in vivo with syngeneic male cells, could not respond in vitro to male spleen cell stimulation if the mice were pretreated with cyclophosphamide. These results suggest that the precursor cells for H-2-restricted cytotoxic responses belong to a different T-cell subpopulation than the precursor cells for allogeneic responses."} {"id": "PMID:153951", "title": "Enzyme histochemistry on skeletal muscle of the human foetus.", "content": "The differentiation of fibre types in developing human skeletal muscle was studied. The material consisted of muscle samples from different muscles of 86 foetuses (abortions) between 12 weeks gestation and delivery and 50 children 1 day to 7 years old. The latter samples were obtained at surgery. Histochemical stains for myofibrillar ATPase were made after preincubations at pH 4.3, 4.6 and 10.3 in order to identify the subgroups A and B of type II fibres and undifferentiated fibres (type II C). Stains for glycogen and lipids were also performed as well as for NADH-diaphorase and alpha-glycerophosphate dehydrogenase. After 20 weeks gestation a few large size type I fibers could be found in some muscles, but not until after the 30th week were some type II A fibres seen. During the last 3 months of gestation a very rapid further differentiation occurred, but at delivery the differentiation process was still not completed. At birth 15-20% of the fibres were classified as undifferentiated. This picture only gradually changed with a slow increase in the number of type I, II A and II B fibres. The stains for metabolic enzymes and substrates were pale until late in foetal life when some distinction between fibre types became discernible.", "contents": "Enzyme histochemistry on skeletal muscle of the human foetus. The differentiation of fibre types in developing human skeletal muscle was studied. The material consisted of muscle samples from different muscles of 86 foetuses (abortions) between 12 weeks gestation and delivery and 50 children 1 day to 7 years old. The latter samples were obtained at surgery. Histochemical stains for myofibrillar ATPase were made after preincubations at pH 4.3, 4.6 and 10.3 in order to identify the subgroups A and B of type II fibres and undifferentiated fibres (type II C). Stains for glycogen and lipids were also performed as well as for NADH-diaphorase and alpha-glycerophosphate dehydrogenase. After 20 weeks gestation a few large size type I fibers could be found in some muscles, but not until after the 30th week were some type II A fibres seen. During the last 3 months of gestation a very rapid further differentiation occurred, but at delivery the differentiation process was still not completed. At birth 15-20% of the fibres were classified as undifferentiated. This picture only gradually changed with a slow increase in the number of type I, II A and II B fibres. The stains for metabolic enzymes and substrates were pale until late in foetal life when some distinction between fibre types became discernible."} {"id": "PMID:153952", "title": "Some quantitative biochemical evaluations of developing skeletal muscles in the human foetus.", "content": "This study was performed to obtain a more precise quantitative estimation of oxidative and glycolytic potentials and stores of various substrates of the muscles in the human foetus. The material consisted of muscle samples from different muscles, a total of 166 muscle specimens from 65 foetuses and 55 skeletal muscle specimens from 53 infants and children. The latter samples were obtained at surgery. The activities for succinate dehydrogenase and phosphofructokinase were chosen as markers for mitochondrial and cytoplasmatic enzymes respectively. Glycogen, triglyceride and phosphagen levels were studied. Water and protein content of the muscle tissue undergo continuous changes during foetal life and were therefore also included in the study. The SDH activity was low during gestation and reached a value of 2-3 mmoles/kg w.wt. X min at delivery. The PFK activity was also low during gestation, but around 25 weeks gestation a value of 3-4 mmoles/kg w.wt. X min was common, and around delivery time about 7 mmoles/kg w.wt. X min. At 1-5 years the PFK activity was around 11-12 mmoles/kg w.wt. X min, which is similar to adult muscles. Glycogen content varied, but increased during gestation. In the last trimester of gestation a value of 62-92 mmoles units/kg w.wt. was found. The triglyceride content at the end of the gestation time was 3-16 mmoles glycerol/kg w.wt. The phosphagen levels were quite low all through foetal life, averaging between 0.5 and 3 mmoles/kg for ATP and CP concentrations.", "contents": "Some quantitative biochemical evaluations of developing skeletal muscles in the human foetus. This study was performed to obtain a more precise quantitative estimation of oxidative and glycolytic potentials and stores of various substrates of the muscles in the human foetus. The material consisted of muscle samples from different muscles, a total of 166 muscle specimens from 65 foetuses and 55 skeletal muscle specimens from 53 infants and children. The latter samples were obtained at surgery. The activities for succinate dehydrogenase and phosphofructokinase were chosen as markers for mitochondrial and cytoplasmatic enzymes respectively. Glycogen, triglyceride and phosphagen levels were studied. Water and protein content of the muscle tissue undergo continuous changes during foetal life and were therefore also included in the study. The SDH activity was low during gestation and reached a value of 2-3 mmoles/kg w.wt. X min at delivery. The PFK activity was also low during gestation, but around 25 weeks gestation a value of 3-4 mmoles/kg w.wt. X min was common, and around delivery time about 7 mmoles/kg w.wt. X min. At 1-5 years the PFK activity was around 11-12 mmoles/kg w.wt. X min, which is similar to adult muscles. Glycogen content varied, but increased during gestation. In the last trimester of gestation a value of 62-92 mmoles units/kg w.wt. was found. The triglyceride content at the end of the gestation time was 3-16 mmoles glycerol/kg w.wt. The phosphagen levels were quite low all through foetal life, averaging between 0.5 and 3 mmoles/kg for ATP and CP concentrations."} {"id": "PMID:153953", "title": "Studies on levamisole, a potentially useful drug in the treatment of Beh\u00e7et's syndrome.", "content": "The anthelmintic drug, levamisole, was shown to amplify the response of human peripheral blood lymphocytes to vegetable mitogens. A similar enhancement of blast formation in the mixed lymphocyte culture was also demonstrated. High concentrations of the drug led to depression of both of these responses. These observations led to studies in a rat breast cancer model in which immunopotentiation was demonstrated in vivo, and this effect was associated with tumor regression. As in the human in vitro studies, high doses of the drug were not associated with augmentation of the immune response and in this circumstance no inhibition of tumor growth was observed. Assuming that potentiation of immune responsiveness is of benefit to patients suffering from Beh\u00e7et's syndrome, the development of clinical trials employing levamisole appears justified, as long as the drug dosage is carefully monitored.", "contents": "Studies on levamisole, a potentially useful drug in the treatment of Beh\u00e7et's syndrome. The anthelmintic drug, levamisole, was shown to amplify the response of human peripheral blood lymphocytes to vegetable mitogens. A similar enhancement of blast formation in the mixed lymphocyte culture was also demonstrated. High concentrations of the drug led to depression of both of these responses. These observations led to studies in a rat breast cancer model in which immunopotentiation was demonstrated in vivo, and this effect was associated with tumor regression. As in the human in vitro studies, high doses of the drug were not associated with augmentation of the immune response and in this circumstance no inhibition of tumor growth was observed. Assuming that potentiation of immune responsiveness is of benefit to patients suffering from Beh\u00e7et's syndrome, the development of clinical trials employing levamisole appears justified, as long as the drug dosage is carefully monitored."} {"id": "PMID:153967", "title": "Comment on \"personality organization as an aspect of back pain in a medical setting\".", "content": "The methodology and results of a recent investigation by Louks, Freeman, and Calsyn (1978) are reviewed. It is demonstrated that the results may have been confounded by inappropriate experimental procedures. Regardless of the methodological deficiencies associated with the experimental procedures, the results do not provide adequate support for the continued differentiation of individual low back pain patients with respect to the etiology of their pain. It is suggested that psychologists may best contribute to the assessment and treatment of individual pain patients by developing actuarial rules regarding the pain-related behavioral characteristics shared by members of various patient subgroups and the specific treatments to which subgroup members best respond.", "contents": "Comment on \"personality organization as an aspect of back pain in a medical setting\". The methodology and results of a recent investigation by Louks, Freeman, and Calsyn (1978) are reviewed. It is demonstrated that the results may have been confounded by inappropriate experimental procedures. Regardless of the methodological deficiencies associated with the experimental procedures, the results do not provide adequate support for the continued differentiation of individual low back pain patients with respect to the etiology of their pain. It is suggested that psychologists may best contribute to the assessment and treatment of individual pain patients by developing actuarial rules regarding the pain-related behavioral characteristics shared by members of various patient subgroups and the specific treatments to which subgroup members best respond."} {"id": "PMID:153969", "title": "Effects of brain serotonin alterations on prostaglandin E1-induced bradycardia in rats.", "content": "The vasodepressor and bradycardia responses of saline control, serotonin-depleted and serotonin-potentiated rats to an intravenous dose of prostaglandin E1 (PGE1) were assessed under the urethane anesthesia. Elevation of serotonin concentration in brain with either 5-hydroxytryptophan (a serotonin precursor) or chlorimipramine (an inhibitor of serotonin reuptake), although causing no changes in vasodepressor reuptake), although causing no changes in vasodepressor response, did enhance the PGE1-induced bradycardia in contrast, depleting serotonin concentration in brain with either p-chlorophenylalanine or 5,7-dihydroxytryptamine greatly reduced the PGE1-induced bradycardia without changes in vasodepressor response. Moreover, the reduced PGE1 bradycardia induced by p-chlorophenylalanine treatment was readily reversed by the replacement of the depleted brain serotonin with 5-hydroxytryptophan in combination with a peripheral decarboxylase inhibitor Ro4-4602. The data indicate that brain serotonergic systems play a role in the elaboration or modulation of the PGE1-induced bradycardia. Specifically, brain serotonin seems to facilitate the PGE1-induced bradycardia since its depletion causes a decrease and its potentiation or elevation causes an increase in the PGE1-induced bradycardia.", "contents": "Effects of brain serotonin alterations on prostaglandin E1-induced bradycardia in rats. The vasodepressor and bradycardia responses of saline control, serotonin-depleted and serotonin-potentiated rats to an intravenous dose of prostaglandin E1 (PGE1) were assessed under the urethane anesthesia. Elevation of serotonin concentration in brain with either 5-hydroxytryptophan (a serotonin precursor) or chlorimipramine (an inhibitor of serotonin reuptake), although causing no changes in vasodepressor reuptake), although causing no changes in vasodepressor response, did enhance the PGE1-induced bradycardia in contrast, depleting serotonin concentration in brain with either p-chlorophenylalanine or 5,7-dihydroxytryptamine greatly reduced the PGE1-induced bradycardia without changes in vasodepressor response. Moreover, the reduced PGE1 bradycardia induced by p-chlorophenylalanine treatment was readily reversed by the replacement of the depleted brain serotonin with 5-hydroxytryptophan in combination with a peripheral decarboxylase inhibitor Ro4-4602. The data indicate that brain serotonergic systems play a role in the elaboration or modulation of the PGE1-induced bradycardia. Specifically, brain serotonin seems to facilitate the PGE1-induced bradycardia since its depletion causes a decrease and its potentiation or elevation causes an increase in the PGE1-induced bradycardia."} {"id": "PMID:153975", "title": "Trisomy 21 with 47,+18 lymphocyte cell line: double mitotic nondisjunction.", "content": "A patient with Down's syndrome was found to have 47,XX,+18/47,XX,+21 mosaicism. Chromosome 18 trisomy was found only in 18% of lymphocytes and not in skin fibroblasts. A likely interpretation is double nondisjunction in a single lymphocyte precursor of a trisomy 21 embryo. A brief review of other cases of mitotic multiple nondisjunction and double aneuploid mosiacism is presented.", "contents": "Trisomy 21 with 47,+18 lymphocyte cell line: double mitotic nondisjunction. A patient with Down's syndrome was found to have 47,XX,+18/47,XX,+21 mosaicism. Chromosome 18 trisomy was found only in 18% of lymphocytes and not in skin fibroblasts. A likely interpretation is double nondisjunction in a single lymphocyte precursor of a trisomy 21 embryo. A brief review of other cases of mitotic multiple nondisjunction and double aneuploid mosiacism is presented."} {"id": "PMID:153980", "title": "Adverse reactions to cromolyn.", "content": "The frequency of adverse reactions (dermatitis, myositis, and gastroenteritis) to cromolyn sodium in asthmatic patients was 2% (B/375). Reactions were non-life-threatening and completely reversible. Immunologic evaluations, including skin and serum tests for immediate and delayed reactivity, all were negative. Adverse reactions to cromolyn do not appear to be based on an immunologic mechanism. Cromolyn appears to be a safe drug for the treatment of asthma.", "contents": "Adverse reactions to cromolyn. The frequency of adverse reactions (dermatitis, myositis, and gastroenteritis) to cromolyn sodium in asthmatic patients was 2% (B/375). Reactions were non-life-threatening and completely reversible. Immunologic evaluations, including skin and serum tests for immediate and delayed reactivity, all were negative. Adverse reactions to cromolyn do not appear to be based on an immunologic mechanism. Cromolyn appears to be a safe drug for the treatment of asthma."} {"id": "PMID:153984", "title": "Evidence for long-lasting tumor immunity in a syngeneic rat lymphoma model: correlation of in vitro findings with in vivo observations.", "content": "Previous studies concerning the tumor-host relationship in the (C58NT)D rat tumor system indicated that some T-lymphocyte responses against tumor antigens were only transiently detectable after tumor inoculation; however, more sensitive procedures for the detection of proliferative responses in the mixed lymphocyte-tumor interaction (MLTI ) have been developed. Upon reexamination of the kinetics of this response, positive responses were detected as long as 650 days after inoculation. Cytotoxic effector cells could be generated in MLTI with lymphocytes from immune WF rats as long as 1 year after inoculation, and evidence was provided which indicated that the persistence of the responses observed in vitro correlated well with the resistance of immune rats to rechallenge with (C58NT)D tumor cells in vivo.", "contents": "Evidence for long-lasting tumor immunity in a syngeneic rat lymphoma model: correlation of in vitro findings with in vivo observations. Previous studies concerning the tumor-host relationship in the (C58NT)D rat tumor system indicated that some T-lymphocyte responses against tumor antigens were only transiently detectable after tumor inoculation; however, more sensitive procedures for the detection of proliferative responses in the mixed lymphocyte-tumor interaction (MLTI ) have been developed. Upon reexamination of the kinetics of this response, positive responses were detected as long as 650 days after inoculation. Cytotoxic effector cells could be generated in MLTI with lymphocytes from immune WF rats as long as 1 year after inoculation, and evidence was provided which indicated that the persistence of the responses observed in vitro correlated well with the resistance of immune rats to rechallenge with (C58NT)D tumor cells in vivo."} {"id": "PMID:153988", "title": "Total correction of tetralogy of Fallot. How to deal with the complicated ascending aorta-right pulmonary artery anastomosis.", "content": "Ascending aorta-right pulmonary artery anastomosis may be complicated by deformity at the anastomotic site leading to discontinuity between pulmonary artery branches. Simple closure of such shunts through the ascending aorta is associated with residual stenosis and pressure gradients. An alternative approach which allows reconstruction of the entire intrapericardial pulmonary arterial system at the initial corrective operation is described. The transection of the ascending aorta facilitates the exposure necessary for this extensive repair. Two illustrative cases are presented.", "contents": "Total correction of tetralogy of Fallot. How to deal with the complicated ascending aorta-right pulmonary artery anastomosis. Ascending aorta-right pulmonary artery anastomosis may be complicated by deformity at the anastomotic site leading to discontinuity between pulmonary artery branches. Simple closure of such shunts through the ascending aorta is associated with residual stenosis and pressure gradients. An alternative approach which allows reconstruction of the entire intrapericardial pulmonary arterial system at the initial corrective operation is described. The transection of the ascending aorta facilitates the exposure necessary for this extensive repair. Two illustrative cases are presented."} {"id": "PMID:153989", "title": "Repair of pulmonary arterial stenosis after Waterston-Cooley anastomosis.", "content": "Within the spectrum of neonatal congenital cyanotic heart disease, emergent surgery is often necessary to correct profound pulmonary hypoperfusion. An ascending aorto-to-pulmonary artery anastomosis (Waterston-Cooley) has proved to be the preferred procedure in selected patients. A new technique to correct the occasional resultant pulmonary arterial deformity is presented which is performed concomitantly with definitive intracardiac correction.", "contents": "Repair of pulmonary arterial stenosis after Waterston-Cooley anastomosis. Within the spectrum of neonatal congenital cyanotic heart disease, emergent surgery is often necessary to correct profound pulmonary hypoperfusion. An ascending aorto-to-pulmonary artery anastomosis (Waterston-Cooley) has proved to be the preferred procedure in selected patients. A new technique to correct the occasional resultant pulmonary arterial deformity is presented which is performed concomitantly with definitive intracardiac correction."} {"id": "PMID:153990", "title": "Calcium sensitivity of myocardial actomyosin ATPase in young and mature male Fischer rats. A brief note.", "content": "Although myocardial actomyosin ATPase specific activity determined at Ca2+ levels of 1 x 10(-3) to 1 x 10(-2) M is consistently higher in two-month old male Fischer rats than in twelve-month old individuals, this difference can be eliminated if the enzyme is assayed at lower calcium concentrations. This suggests that the previously reported, declining actomyosin ATPase activity in the rat myocardium with advancing age may represent an age-related diminished ability of calcium to reverse the known inhibition upon actomyosin ATPase by the regulatory proteins.", "contents": "Calcium sensitivity of myocardial actomyosin ATPase in young and mature male Fischer rats. A brief note. Although myocardial actomyosin ATPase specific activity determined at Ca2+ levels of 1 x 10(-3) to 1 x 10(-2) M is consistently higher in two-month old male Fischer rats than in twelve-month old individuals, this difference can be eliminated if the enzyme is assayed at lower calcium concentrations. This suggests that the previously reported, declining actomyosin ATPase activity in the rat myocardium with advancing age may represent an age-related diminished ability of calcium to reverse the known inhibition upon actomyosin ATPase by the regulatory proteins."} {"id": "PMID:153992", "title": "[The inhibitor factor of leukocyte migration in acne vulgaris].", "content": "The inhibition factor of the leukocytic migration was studied in 26 patients with Acne Vulgaris, stages III and IV, being positive in all the cases. The LIF positive shows the mobilisation of lymphocytic population, answering an active and constant immunologic conflict. As the PA is antigenic, because it produces a blastification (TTL positive), we can say that it acts as antigen provoking immunologic mechanisms with help to explain the inflammatory process at the pilosebaceous follicle in the AV.", "contents": "[The inhibitor factor of leukocyte migration in acne vulgaris]. The inhibition factor of the leukocytic migration was studied in 26 patients with Acne Vulgaris, stages III and IV, being positive in all the cases. The LIF positive shows the mobilisation of lymphocytic population, answering an active and constant immunologic conflict. As the PA is antigenic, because it produces a blastification (TTL positive), we can say that it acts as antigen provoking immunologic mechanisms with help to explain the inflammatory process at the pilosebaceous follicle in the AV."} {"id": "PMID:154003", "title": "The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer.", "content": "The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.", "contents": "The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer. The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S."} {"id": "PMID:154004", "title": "The cytoskeleton and cell movement: general considerations.", "content": "The cytoskeletal proteins, actin, myosin, tubulin, dynein, and their associated proteins, are discussed selectively with regards to their biochemical and structural properties. Particular emphasis is placed on the comparison of non-muscle proteins to their muscle counterparts, and on the various mechanisms for regulating actin polymerization, actin-myosin interaction, and tubulin polymerization. This review as well as the bibliography accompanying it is selective. An attempt is made to stress the most recent findings and to emphasize those areas which appear to hold the greatest promise for future research.", "contents": "The cytoskeleton and cell movement: general considerations. The cytoskeletal proteins, actin, myosin, tubulin, dynein, and their associated proteins, are discussed selectively with regards to their biochemical and structural properties. Particular emphasis is placed on the comparison of non-muscle proteins to their muscle counterparts, and on the various mechanisms for regulating actin polymerization, actin-myosin interaction, and tubulin polymerization. This review as well as the bibliography accompanying it is selective. An attempt is made to stress the most recent findings and to emphasize those areas which appear to hold the greatest promise for future research."} {"id": "PMID:154000", "title": "[Long-term complex plan for technical reorganization of technological processes].", "content": "New technological processes introduced in the manufacturing combine \"Krasnogvardeets\" and planned for adopting conformable to a long-range complex programme of technical reorganization of technological processes are briefly described.", "contents": "[Long-term complex plan for technical reorganization of technological processes]. New technological processes introduced in the manufacturing combine \"Krasnogvardeets\" and planned for adopting conformable to a long-range complex programme of technical reorganization of technological processes are briefly described."} {"id": "PMID:154001", "title": "[Experience in developing and introducing a system of defect-free work as a stage in creating a complex system of production quality control].", "content": "An experience in working out and introduction of a system of failure-free performance work as one of the most important steps in creating a complex system for the production quality control at the Leningrad combine \"Krasnogvardeets\" is described. Issues related to elaborating, introduction and further improving the system of the failure-free work, its pecuniary stimulation and setting up standards for the enterprise are discussed. Under consideration are also problems of organizing a unitized service for the quantity control, as an organ called to secure coordination and quidance over these operations at the combine in this industry.", "contents": "[Experience in developing and introducing a system of defect-free work as a stage in creating a complex system of production quality control]. An experience in working out and introduction of a system of failure-free performance work as one of the most important steps in creating a complex system for the production quality control at the Leningrad combine \"Krasnogvardeets\" is described. Issues related to elaborating, introduction and further improving the system of the failure-free work, its pecuniary stimulation and setting up standards for the enterprise are discussed. Under consideration are also problems of organizing a unitized service for the quantity control, as an organ called to secure coordination and quidance over these operations at the combine in this industry."} {"id": "PMID:154002", "title": "[Experience in developing and manufacturing anesthetic-respiratory apparatus in the \"Red Guard\" combine].", "content": "Unification of basic subassemblies in the apparatus for inhalation anesthesia and artificial ventilation of the lungs is in wide practice. This helped achieve a high quality of the manufactured units with the diversity of models for the anesthetic-respiratory apparatus, put out by the Leningrad manufacturing combine \"Krasnogvardeets\".", "contents": "[Experience in developing and manufacturing anesthetic-respiratory apparatus in the \"Red Guard\" combine]. Unification of basic subassemblies in the apparatus for inhalation anesthesia and artificial ventilation of the lungs is in wide practice. This helped achieve a high quality of the manufactured units with the diversity of models for the anesthetic-respiratory apparatus, put out by the Leningrad manufacturing combine \"Krasnogvardeets\"."} {"id": "PMID:154055", "title": "Reversion and interallelic complementation at four urease loci in Neurospora crassa.", "content": "Analysis of heat stability of urease in extracts of 24 revertants, six for each of four ure loci, revealed that at least one revertant for each locus had a heat stability about one-third that of wild type. Similar results were obtained with urease formed by interallelic complementation at the ure-2 and ure-4 loci, but interallelic complementation at the ure-1 and ure-3 loci produced insufficient urease activity for analysis. The data are interpreted to suggest, as a tentative model, a structural function for each of the four ure loci.", "contents": "Reversion and interallelic complementation at four urease loci in Neurospora crassa. Analysis of heat stability of urease in extracts of 24 revertants, six for each of four ure loci, revealed that at least one revertant for each locus had a heat stability about one-third that of wild type. Similar results were obtained with urease formed by interallelic complementation at the ure-2 and ure-4 loci, but interallelic complementation at the ure-1 and ure-3 loci produced insufficient urease activity for analysis. The data are interpreted to suggest, as a tentative model, a structural function for each of the four ure loci."} {"id": "PMID:154056", "title": "Sterol content and enzyme defects of nystatin-resistant mutants of Neurospora crassa.", "content": "Non-saponifiable cell extracts of wild type and sterol mutants of N. crassa were analysed by means of gas-liquid chromatography. The wild-type contained ergosterol and episertol in a 10:1 ratio. None of the mutants was able to synthesize ergosterol. Three of the mutants carry single recessive gene mutations cauisng blocks in the terminal steps of ergosterol biosynthesis: erg-1 has an inactive delta 8 leads to delta 7 isomerase erg-2 has an inactive 24(28) hydrogenase, and erg-4 has an inactive C-24 methyl transferase. Some of the mutants accumulated novel sterols as a result of their enzyme defects. The genes erg-1 and erg-2 were mapped close to inl on the right arm of chromosome V.", "contents": "Sterol content and enzyme defects of nystatin-resistant mutants of Neurospora crassa. Non-saponifiable cell extracts of wild type and sterol mutants of N. crassa were analysed by means of gas-liquid chromatography. The wild-type contained ergosterol and episertol in a 10:1 ratio. None of the mutants was able to synthesize ergosterol. Three of the mutants carry single recessive gene mutations cauisng blocks in the terminal steps of ergosterol biosynthesis: erg-1 has an inactive delta 8 leads to delta 7 isomerase erg-2 has an inactive 24(28) hydrogenase, and erg-4 has an inactive C-24 methyl transferase. Some of the mutants accumulated novel sterols as a result of their enzyme defects. The genes erg-1 and erg-2 were mapped close to inl on the right arm of chromosome V."} {"id": "PMID:154059", "title": "Characterization of the plasma membrane ATPase of Saccharomyces cerevisiae.", "content": "1. The distribution of ATPase and several marker enzymes was examined after differential and sucrose gradient centrifugation of yeast homogenates. 2. An ATPase activity not sensitive to oligomycin is found exclusively associated with a particulate fraction equilibrating at densities of 1.23-1.25. This particulate material shows the chemical and enzymatic characteristics of the yeast plasma membrane. 3. The pH optimum of the plasma membrane ATPase is 5.6, as compared with 8.5 for the mitochondrial ATPase. In addition to oligomycin, the enzyme is not sensitive to other inhibitors of the mitochondrial ATPase as azide, dicyclohexylcarbodiimide and the mitochondrial ATPase inhibitor protein. It is inhibited by p-chloromercuryphenyl sulfonate, fluoride, quercetin and by the antibiotic Dio-9 but is not affected by ouabain. 4. The plasma membrane ATPase shows a high affinity for ATP (Km = 0.1 mM) and is very specific for this compound, hydrolyzing other nucleotide triphosphates less than 25% as rapidly. No activity was detected with ADP. 5. The enzyme requires a divalent cation for activity and Mg2+ is the most effective. It is not significantly stimulated by K+ or bicarbonate and Ca2+ is inhibitory. 6. The activity cannot be assayed in intact cells unless they are permeabilized with toluene. This suggest that the active site is on the cytoplasmic side of the plasma membrane.", "contents": "Characterization of the plasma membrane ATPase of Saccharomyces cerevisiae. 1. The distribution of ATPase and several marker enzymes was examined after differential and sucrose gradient centrifugation of yeast homogenates. 2. An ATPase activity not sensitive to oligomycin is found exclusively associated with a particulate fraction equilibrating at densities of 1.23-1.25. This particulate material shows the chemical and enzymatic characteristics of the yeast plasma membrane. 3. The pH optimum of the plasma membrane ATPase is 5.6, as compared with 8.5 for the mitochondrial ATPase. In addition to oligomycin, the enzyme is not sensitive to other inhibitors of the mitochondrial ATPase as azide, dicyclohexylcarbodiimide and the mitochondrial ATPase inhibitor protein. It is inhibited by p-chloromercuryphenyl sulfonate, fluoride, quercetin and by the antibiotic Dio-9 but is not affected by ouabain. 4. The plasma membrane ATPase shows a high affinity for ATP (Km = 0.1 mM) and is very specific for this compound, hydrolyzing other nucleotide triphosphates less than 25% as rapidly. No activity was detected with ADP. 5. The enzyme requires a divalent cation for activity and Mg2+ is the most effective. It is not significantly stimulated by K+ or bicarbonate and Ca2+ is inhibitory. 6. The activity cannot be assayed in intact cells unless they are permeabilized with toluene. This suggest that the active site is on the cytoplasmic side of the plasma membrane."} {"id": "PMID:154060", "title": "[\"Ischias antica et postica.\" A scheme of neurological investigation (author's transl)].", "content": "A scheme of neurological investigation is presented which combines anamnesis, clinical findings, electrophysiological data, course and postoperative documentation for the radicular processes of the lumbo-sacral region (ischias antica et postica).", "contents": "[\"Ischias antica et postica.\" A scheme of neurological investigation (author's transl)]. A scheme of neurological investigation is presented which combines anamnesis, clinical findings, electrophysiological data, course and postoperative documentation for the radicular processes of the lumbo-sacral region (ischias antica et postica)."} {"id": "PMID:154058", "title": "Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications.", "content": "The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.", "contents": "Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications. The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition."} {"id": "PMID:154062", "title": "Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange.", "content": "By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative.", "contents": "Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange. By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative."} {"id": "PMID:154072", "title": "Spinal subdural empyema: report of two cases.", "content": "Spinal subdural empyema (SSE) is a rare variety of intraspinal infection. SSE should be suspected in patients presenting with fever, back pain, and signs of cord or nerve root compression. Two patients with SSE are presented. The first patient complained of fever and back pain. She had no neurological deficit but was found to have SSE. The second patient, who presented with intracerebral hemorrhage in the fifth month of pregnancy and spontaneous abortion, was found to have SSE at lumbar puncture. The clinical manifestations and management are discussed.", "contents": "Spinal subdural empyema: report of two cases. Spinal subdural empyema (SSE) is a rare variety of intraspinal infection. SSE should be suspected in patients presenting with fever, back pain, and signs of cord or nerve root compression. Two patients with SSE are presented. The first patient complained of fever and back pain. She had no neurological deficit but was found to have SSE. The second patient, who presented with intracerebral hemorrhage in the fifth month of pregnancy and spontaneous abortion, was found to have SSE at lumbar puncture. The clinical manifestations and management are discussed."} {"id": "PMID:154073", "title": "Spinal subarachnoid hematoma after lumbar puncture producing acute thoracic myelopathy: case report.", "content": "A case of subarachnoid hematoma after a difficult lumbar puncture and anticoagulation is presented. Subarachnoid adhesions preventing the free flow of spinal fluid at the T-6 level served to limit the cranial progression of the hemorrhage and produced a transverse myelopathy at that level. The underlying pathology, clinical course, and myelographic findings are reviewed. Pertinent literature is presented.", "contents": "Spinal subarachnoid hematoma after lumbar puncture producing acute thoracic myelopathy: case report. A case of subarachnoid hematoma after a difficult lumbar puncture and anticoagulation is presented. Subarachnoid adhesions preventing the free flow of spinal fluid at the T-6 level served to limit the cranial progression of the hemorrhage and produced a transverse myelopathy at that level. The underlying pathology, clinical course, and myelographic findings are reviewed. Pertinent literature is presented."} {"id": "PMID:154085", "title": "The cornea in connective tissue diseases.", "content": "Even though lenticular and retinal abnormalities seem to dominate the ophthalmologic picture in Marfan's syndrome, the cornea shows significant abnormalities consisting of a striking flattening and corneal astigmatism. The use of conjunctival biopsies followed by histochemical and electron-microscopic evaluation shows low morbidity but an excellent yield of diagnostic information on storage diseases, and an ectopic collagen may be the basis of at least one type of keratoconus. Much more work has to be done on defining the collagens of the human eye in embryologic, fetal, and postnatal stages under normal and pathologic conditions. The yield of such studies may be high for an understanding of such diseases as myopia, retinal detachment, and keratoconus.", "contents": "The cornea in connective tissue diseases. Even though lenticular and retinal abnormalities seem to dominate the ophthalmologic picture in Marfan's syndrome, the cornea shows significant abnormalities consisting of a striking flattening and corneal astigmatism. The use of conjunctival biopsies followed by histochemical and electron-microscopic evaluation shows low morbidity but an excellent yield of diagnostic information on storage diseases, and an ectopic collagen may be the basis of at least one type of keratoconus. Much more work has to be done on defining the collagens of the human eye in embryologic, fetal, and postnatal stages under normal and pathologic conditions. The yield of such studies may be high for an understanding of such diseases as myopia, retinal detachment, and keratoconus."} {"id": "PMID:154090", "title": "Counseling the parents of birth-defective children.", "content": "Parents of a child who is diagnosed as defective face a crisis for which they are usually unprepared. They need an opportunity to work through their intense feelings. In addition, they need specific information about how to be of use to their child. Self-help groups composed of parents of children with a similar handicap can be a resource of great value during this crisis as well as in the years that follow. When such groups are not available, parents can be placed in contact with a family that is effectively raising a child with the same handicap or an adult who has successfully coped with it. Physicians should be aware of their own feelings regarding handicaps and of the effect these may have on efforts to help parents.", "contents": "Counseling the parents of birth-defective children. Parents of a child who is diagnosed as defective face a crisis for which they are usually unprepared. They need an opportunity to work through their intense feelings. In addition, they need specific information about how to be of use to their child. Self-help groups composed of parents of children with a similar handicap can be a resource of great value during this crisis as well as in the years that follow. When such groups are not available, parents can be placed in contact with a family that is effectively raising a child with the same handicap or an adult who has successfully coped with it. Physicians should be aware of their own feelings regarding handicaps and of the effect these may have on efforts to help parents."} {"id": "PMID:154100", "title": "The role of methylprednisolone in the modulation of cellular cytotoxicity and its relation to renal transplantation.", "content": "Inhibition of killer cell generation or suppression of their cytolytic capacity once formed represent fundamental mechanisms by which methylprednisolone may modulate cellular cytotoxicity in the transplant recipient. In vitro studies in mixed lymphocyte culture demonstrated that the presence of therapeutic concentrations of this agent (0.001-1 microgram/ml) during the sensitisation phase resulted in suppression of lymphocyte activation without cytolysis and marked or total inhibition of killer cell generation. A considerable individual variation in sensitivity to methylprednisolone-induced suppression was observed and killer cells once generated were resistant to this agent.", "contents": "The role of methylprednisolone in the modulation of cellular cytotoxicity and its relation to renal transplantation. Inhibition of killer cell generation or suppression of their cytolytic capacity once formed represent fundamental mechanisms by which methylprednisolone may modulate cellular cytotoxicity in the transplant recipient. In vitro studies in mixed lymphocyte culture demonstrated that the presence of therapeutic concentrations of this agent (0.001-1 microgram/ml) during the sensitisation phase resulted in suppression of lymphocyte activation without cytolysis and marked or total inhibition of killer cell generation. A considerable individual variation in sensitivity to methylprednisolone-induced suppression was observed and killer cells once generated were resistant to this agent."} {"id": "PMID:154101", "title": "Cytogenetic analysis on children born of parents treated with immunosuppressive drugs.", "content": "Two women previously treated with cyclophosphamide had five pregnancies, resulting in seven normal offspring, including two sets of twins. All the babies had normal chromosome constitution and there was no significant chromosome damage. Apart from the twin pregnancies, which were induced, the pregnancies continued to full term and the birth weights were good. Men with renal transplants receiving azathioprine and prednisolone fathered 13 pregnancies, resulting in 11 offspring; one was a mongol; there were two spontaneous abortions, including a twin pregnancy. With the exception of the mongol, the babies had normal chromosome constitution and there was no significant chromosome damage. Two women with renal transplants receiving azathioprine and prednisolone have had four pregnancies, two ended in spontaneous abortion and two continue.", "contents": "Cytogenetic analysis on children born of parents treated with immunosuppressive drugs. Two women previously treated with cyclophosphamide had five pregnancies, resulting in seven normal offspring, including two sets of twins. All the babies had normal chromosome constitution and there was no significant chromosome damage. Apart from the twin pregnancies, which were induced, the pregnancies continued to full term and the birth weights were good. Men with renal transplants receiving azathioprine and prednisolone fathered 13 pregnancies, resulting in 11 offspring; one was a mongol; there were two spontaneous abortions, including a twin pregnancy. With the exception of the mongol, the babies had normal chromosome constitution and there was no significant chromosome damage. Two women with renal transplants receiving azathioprine and prednisolone have had four pregnancies, two ended in spontaneous abortion and two continue."} {"id": "PMID:154103", "title": "Interaction of RNA polymerase and rho in transcription termination: coupled ATPase.", "content": "We have previously described temperature sensitive rho mutants of Escherichia coli (e.g., rho15) that are defective in transcription termination at various signals, including an IS2 DNA insertion in the gal operon [Das, A., Court, D. & Adhya, S. (1976) Proc. Natl. Acad. Sci. USA, 73, 1959-1963]. In this paper, we report the isolation of mutants altered in the beta subunit of RNA polymerase (a class of Rifampicin-resistant mutants), which restore gal IS2 polarity in the rho 15 strain. It has been shown that one of these suppressor RNA polymerases (rpoB101) requires rho to terminate transcription of phage lambda mRNA. In contrast to the wild type RNA polymerase, the suppressor RNA polymerase also terminates lambda mRNA transcription in the presence of rho15 protein. We have isolated new rho mutants (e.g., rho112) that are defective in transcription termination in the rpoB101 strain. These results strongly support the notion that rho and RNA polymerase interact functionally during transcription termination. We have shown that rho15 catalyzes ATP hydrolysis during transcription with rpoB101 RNA polymerase, but not with wild-type RNA polymerase. Because rho 15 protein hydrolyzes ATP in the presence of free RNA, we suggest that rho may recognize the 3'-OH end of RNA. During transcription, this recognition involves an interaction with RNA polymerase, resulting in the displacement of the polymerase and the release of the nascent mRNA.", "contents": "Interaction of RNA polymerase and rho in transcription termination: coupled ATPase. We have previously described temperature sensitive rho mutants of Escherichia coli (e.g., rho15) that are defective in transcription termination at various signals, including an IS2 DNA insertion in the gal operon [Das, A., Court, D. & Adhya, S. (1976) Proc. Natl. Acad. Sci. USA, 73, 1959-1963]. In this paper, we report the isolation of mutants altered in the beta subunit of RNA polymerase (a class of Rifampicin-resistant mutants), which restore gal IS2 polarity in the rho 15 strain. It has been shown that one of these suppressor RNA polymerases (rpoB101) requires rho to terminate transcription of phage lambda mRNA. In contrast to the wild type RNA polymerase, the suppressor RNA polymerase also terminates lambda mRNA transcription in the presence of rho15 protein. We have isolated new rho mutants (e.g., rho112) that are defective in transcription termination in the rpoB101 strain. These results strongly support the notion that rho and RNA polymerase interact functionally during transcription termination. We have shown that rho15 catalyzes ATP hydrolysis during transcription with rpoB101 RNA polymerase, but not with wild-type RNA polymerase. Because rho 15 protein hydrolyzes ATP in the presence of free RNA, we suggest that rho may recognize the 3'-OH end of RNA. During transcription, this recognition involves an interaction with RNA polymerase, resulting in the displacement of the polymerase and the release of the nascent mRNA."} {"id": "PMID:154104", "title": "Natural killing and antibody-dependent cellular cytotoxicity are independent immune functions in the Minnesota miniature swine.", "content": "Peripheral blood lymphocytes from Minnesota miniature pigs were tested for natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in a 2- to 4-hr 51Cr release assay against human myeloid and lymphoid tumor target cells. Adult specific pathogen-free and germfree animals exhibited normal levels of activity in both assays. In addition, the NK and ADCC activities of peripheral blood lymphocytes from colostrum-deprived newborn piglets were examined. These animals were obtained by hysterectomy and previously shown to be immunologically \"virgin.\" We found that these newborn piglets exhibited normal ADCC but lacked NK activity. The differences in the ontogeny of the two activities suggest that they are distinct. Preliminary effector cell characterization studies suggest that: (i) NK and ADCC in the pig are physically not separable; (ii) the majority of the cytotoxic activity on a cell-per-cell basis is mediated by the non-T lymphocyte fraction; and (iii) the rosetted T cells, which account for about 60% of the total pig peripheral blood lymphocytes, have low but demonstrable cytotoxic activity as well.", "contents": "Natural killing and antibody-dependent cellular cytotoxicity are independent immune functions in the Minnesota miniature swine. Peripheral blood lymphocytes from Minnesota miniature pigs were tested for natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in a 2- to 4-hr 51Cr release assay against human myeloid and lymphoid tumor target cells. Adult specific pathogen-free and germfree animals exhibited normal levels of activity in both assays. In addition, the NK and ADCC activities of peripheral blood lymphocytes from colostrum-deprived newborn piglets were examined. These animals were obtained by hysterectomy and previously shown to be immunologically \"virgin.\" We found that these newborn piglets exhibited normal ADCC but lacked NK activity. The differences in the ontogeny of the two activities suggest that they are distinct. Preliminary effector cell characterization studies suggest that: (i) NK and ADCC in the pig are physically not separable; (ii) the majority of the cytotoxic activity on a cell-per-cell basis is mediated by the non-T lymphocyte fraction; and (iii) the rosetted T cells, which account for about 60% of the total pig peripheral blood lymphocytes, have low but demonstrable cytotoxic activity as well."} {"id": "PMID:154105", "title": "Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice.", "content": "Dendrite cells (DCs) are a new cell type initially identified in mouse lymphoid organs. Recently, DCs have been purified from mouse spleen. This paper demonstrates a functional role of DCs: they are potent stimulators of the primary mixed leukocytes reaction (MLR). As few as 300-1000 DCs doubled the proliferative activity of 5 X 10(6) allogeneic responder spleen cells, while 0.3-1.0 X 10(5) DCs induced a maximal stimulation of 30- to 80-fold. Between these extremes, the log of the MLR response increased linearly with the log of DC numbers. This dose-response assay was then used to compare the potency of purified DCs with that of other heterogeneous lymphoid populations, many of which gave dose-response curves with similar slopes. The potency of purified DCs as MLR stimulators was 100-300 times greater than that of unfractionated spleen cells. When spleen cells were fractionated by simple physical techniques, MLR-stimulating capacity in the subpopulations correlated closely with DC numbers. Removal of splenic B or T lymphocytes, by anti-immunoglobulin or anti-brain serum plus complement, did not reduce MLR-stimulating capacity. Finally, several populations, enriched in mononuclear phagocytes but lacking in DCs, stimulated weakly if at all. We conclude that DCs are a potent stimulating cell and are at least 100 times more effective than other major cell subclasses--i.e., B and T lymphocytes and macrophages.", "contents": "Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Dendrite cells (DCs) are a new cell type initially identified in mouse lymphoid organs. Recently, DCs have been purified from mouse spleen. This paper demonstrates a functional role of DCs: they are potent stimulators of the primary mixed leukocytes reaction (MLR). As few as 300-1000 DCs doubled the proliferative activity of 5 X 10(6) allogeneic responder spleen cells, while 0.3-1.0 X 10(5) DCs induced a maximal stimulation of 30- to 80-fold. Between these extremes, the log of the MLR response increased linearly with the log of DC numbers. This dose-response assay was then used to compare the potency of purified DCs with that of other heterogeneous lymphoid populations, many of which gave dose-response curves with similar slopes. The potency of purified DCs as MLR stimulators was 100-300 times greater than that of unfractionated spleen cells. When spleen cells were fractionated by simple physical techniques, MLR-stimulating capacity in the subpopulations correlated closely with DC numbers. Removal of splenic B or T lymphocytes, by anti-immunoglobulin or anti-brain serum plus complement, did not reduce MLR-stimulating capacity. Finally, several populations, enriched in mononuclear phagocytes but lacking in DCs, stimulated weakly if at all. We conclude that DCs are a potent stimulating cell and are at least 100 times more effective than other major cell subclasses--i.e., B and T lymphocytes and macrophages."} {"id": "PMID:154114", "title": "Midabdomen abdominoplasty.", "content": "A simple technique is presented for removal of excessive supraumbilical and periumbilical skin.", "contents": "Midabdomen abdominoplasty. A simple technique is presented for removal of excessive supraumbilical and periumbilical skin."} {"id": "PMID:154115", "title": "Suture materials in otoplasty.", "content": "From my experiences in 101 otoplasties of the Mustard\u00e9 type, the buried suture materials have shown individual variations, as regards granuloma and slippage complications. As a result, I now prefer 4/0 clear nylon for reconstruction of the anti-helix, 3/0 white Mersilene for concha-mastoidal fixation, and 4/0 chromic or subcuticular Vicryl for skin closure.", "contents": "Suture materials in otoplasty. From my experiences in 101 otoplasties of the Mustard\u00e9 type, the buried suture materials have shown individual variations, as regards granuloma and slippage complications. As a result, I now prefer 4/0 clear nylon for reconstruction of the anti-helix, 3/0 white Mersilene for concha-mastoidal fixation, and 4/0 chromic or subcuticular Vicryl for skin closure."} {"id": "PMID:154117", "title": "[Diagnosis and differential diagnosis of cardiac enlargement in the chest film. Systematic survey (author's transl)].", "content": "The pathological enlarged heart is attempted to define by roentgenologic criteria. The historical \"heart lung quotient\" continues to be an important measurement. Alterations of the heart size secondary to age, the systolic-diastolic difference of the heart size and the alterations of the heart size between two chest films are discussed. Differential diagnosis of enlargement and shape of the left and right heart are presented. Also the differential diagnosis of general cardiac enlargement especially valvular heart disease, combined left and right heart failure, pericardial effusion and myocardiopathy is considered.", "contents": "[Diagnosis and differential diagnosis of cardiac enlargement in the chest film. Systematic survey (author's transl)]. The pathological enlarged heart is attempted to define by roentgenologic criteria. The historical \"heart lung quotient\" continues to be an important measurement. Alterations of the heart size secondary to age, the systolic-diastolic difference of the heart size and the alterations of the heart size between two chest films are discussed. Differential diagnosis of enlargement and shape of the left and right heart are presented. Also the differential diagnosis of general cardiac enlargement especially valvular heart disease, combined left and right heart failure, pericardial effusion and myocardiopathy is considered."} {"id": "PMID:154121", "title": "The role of the fibrinolytic system in thromboembolism.", "content": "The present concept of physiologic fibrinolysis was reviewed. It was concluded that the nonspecific proteolytic activity of plasmin would essentially be limited to fibrin in vivo in view of (A) the specific adsorption of activator and of plasminogen onto the fibrin surface resulting in local generation of plasmin and (B) the fact that plasmin, adsorbed to fibrin (in contrast to plasmin in the fluid phase) largely escapes from the action of antiplasmin. The hemostatic balance in the resting condition was discussed. It was concluded that under normal conditions, systemic intravascular fibrin deposition or formation must be either nonexistent or extremely limited. On the other hand, there is considerable evidence that a limited systemic fibrinogenolysis is going on in healthy individuals and that this process can be accelerated by simple physiologic procedures, such as strenuous physical exercise.", "contents": "The role of the fibrinolytic system in thromboembolism. The present concept of physiologic fibrinolysis was reviewed. It was concluded that the nonspecific proteolytic activity of plasmin would essentially be limited to fibrin in vivo in view of (A) the specific adsorption of activator and of plasminogen onto the fibrin surface resulting in local generation of plasmin and (B) the fact that plasmin, adsorbed to fibrin (in contrast to plasmin in the fluid phase) largely escapes from the action of antiplasmin. The hemostatic balance in the resting condition was discussed. It was concluded that under normal conditions, systemic intravascular fibrin deposition or formation must be either nonexistent or extremely limited. On the other hand, there is considerable evidence that a limited systemic fibrinogenolysis is going on in healthy individuals and that this process can be accelerated by simple physiologic procedures, such as strenuous physical exercise."} {"id": "PMID:154129", "title": "[Unusual localizations of hydatid cysts].", "content": "In a total of 448 hydatic cysts that have been treated in the I-st Surgery Clinic of Jassy between 1947 and 1977 rare localizations were noted in 61 cases. Of these 47 were primary echinococcoses and 14 were secondary. The clinical and therapeutic aspects are discussed for each particular localization: the splenic localization was encountered in 16 cases, the peritoneal one in 10 cases, the diaphragmatic in 6 cases. There were also 2 renal localizations, 3 retro-peritoneal ones, 3 ovarian and salpyngean localizations, 3 thyroid, 7 endo-thoracic but extra-pulmonary, 5 muscular and 6 subcutaneous localizations. Radical surgery had immediate and late results that were quite satisfactory. No deaths or recidives were noted.", "contents": "[Unusual localizations of hydatid cysts]. In a total of 448 hydatic cysts that have been treated in the I-st Surgery Clinic of Jassy between 1947 and 1977 rare localizations were noted in 61 cases. Of these 47 were primary echinococcoses and 14 were secondary. The clinical and therapeutic aspects are discussed for each particular localization: the splenic localization was encountered in 16 cases, the peritoneal one in 10 cases, the diaphragmatic in 6 cases. There were also 2 renal localizations, 3 retro-peritoneal ones, 3 ovarian and salpyngean localizations, 3 thyroid, 7 endo-thoracic but extra-pulmonary, 5 muscular and 6 subcutaneous localizations. Radical surgery had immediate and late results that were quite satisfactory. No deaths or recidives were noted."} {"id": "PMID:154140", "title": "[Intramedullary nailing with reaming. A critical analysis of Kuntscher's principle (author's transl)].", "content": "The authors have reviewed two of Kuntscher's principles relating to intramedullary nailing: the moment of elasticity of the nail should be close to the moment of elasticity of the bone and the suppression of rotation movements at the fracture site is due to locking of the nail by virtue of its elasticity. They have conducted an experimental study which does not confirm these views. They considered that rotary stability is due to muscle tone, the line of the fracture and the anchorage of the ends of the nail at the upper and lower end of the bone.", "contents": "[Intramedullary nailing with reaming. A critical analysis of Kuntscher's principle (author's transl)]. The authors have reviewed two of Kuntscher's principles relating to intramedullary nailing: the moment of elasticity of the nail should be close to the moment of elasticity of the bone and the suppression of rotation movements at the fracture site is due to locking of the nail by virtue of its elasticity. They have conducted an experimental study which does not confirm these views. They considered that rotary stability is due to muscle tone, the line of the fracture and the anchorage of the ends of the nail at the upper and lower end of the bone."} {"id": "PMID:154141", "title": "[Combined Kuntscher nailing and screw fixation (author's transl)].", "content": "The authors describe a technique of Kuntscher intramedullary nailing combined with screws driven through the bone and the nail above and below the fracture site. This technique gives better stability of the fracture and allows extension of intramedullary nailing to severely comminuted fractures, fractures with loss of bone and to proximal or distal fractures. Risks of rotational instability or shortening are diminished. The technique is fully described. With the use of correct ancillary instruments, x-ray exposure is minimal. Biomechanical experiments conducted to determine the best position of the screws for optimal locking of the nail are described. The results obtained in one hundred and sixteen cases are analysed. The technique was also used in the treatment of non-union and in the fixation of osteotomies.", "contents": "[Combined Kuntscher nailing and screw fixation (author's transl)]. The authors describe a technique of Kuntscher intramedullary nailing combined with screws driven through the bone and the nail above and below the fracture site. This technique gives better stability of the fracture and allows extension of intramedullary nailing to severely comminuted fractures, fractures with loss of bone and to proximal or distal fractures. Risks of rotational instability or shortening are diminished. The technique is fully described. With the use of correct ancillary instruments, x-ray exposure is minimal. Biomechanical experiments conducted to determine the best position of the screws for optimal locking of the nail are described. The results obtained in one hundred and sixteen cases are analysed. The technique was also used in the treatment of non-union and in the fixation of osteotomies."} {"id": "PMID:154142", "title": "[Autologous osteochondral graft: a method for resurfacing osteonecrosis of the medial femoral condyle in the elderly (author's transl)].", "content": "The author describes an original technique for resurfacing osteonecrotic medial femoral condyles. The centre and posterior part of the condyle is displaced anteriorly into the weight-bearing area. The indications for this technique are cases in which there is no deformity in the frontal plane and when the tibial articular cartilage is normal. Two cases were so treated. After a follow up of three and five years the results were very good.", "contents": "[Autologous osteochondral graft: a method for resurfacing osteonecrosis of the medial femoral condyle in the elderly (author's transl)]. The author describes an original technique for resurfacing osteonecrotic medial femoral condyles. The centre and posterior part of the condyle is displaced anteriorly into the weight-bearing area. The indications for this technique are cases in which there is no deformity in the frontal plane and when the tibial articular cartilage is normal. Two cases were so treated. After a follow up of three and five years the results were very good."} {"id": "PMID:154143", "title": "[Evaluation of functional results after fractures of the calcaneus (author's transl)].", "content": "The author describes a scale of rating for the evaluation of the results of fractures of the calcaneus, similar to that used for the evaluation of hip function. Five points are given for walking ability, pain, mobility and triceps power. The last point is considered to be essential. This evaluation was tested on 232 cases. A close correlation was established between the four criteria.", "contents": "[Evaluation of functional results after fractures of the calcaneus (author's transl)]. The author describes a scale of rating for the evaluation of the results of fractures of the calcaneus, similar to that used for the evaluation of hip function. Five points are given for walking ability, pain, mobility and triceps power. The last point is considered to be essential. This evaluation was tested on 232 cases. A close correlation was established between the four criteria."} {"id": "PMID:154144", "title": "[Correction of bowing in Paget's disease (author's transl)].", "content": "Thirteen tibiae and seven femora suffering from bowing due to Paget's disease have been streightened operatively. In the tibiae, the deformities were of metaphysial genu varum with bowing in the sagittal plane of an average of 30 degrees combined with some medial rotation. In the femora, the main curve was anterolateral with some medial rotation and coxa vara. Seventeen cases united uneventfully after osteotomy. In three cases, there were septic complications, union occurred after removal of the internal fixation. Bowing recurred in three cases. The recurrence appeared to be related to incomplete correction leading to persistent mechanical strain on bones affected by rapid bone turnover. Inadequate internal fixation may also be a factor. All other cases were functionally improved by correction. Oblique osteotomy is indicated for the correction of tibial deformity when there is moderate medial rotation. Transverse osteotomy with fixation by intramedullary nailing is indicated for correction of femoral deformities.", "contents": "[Correction of bowing in Paget's disease (author's transl)]. Thirteen tibiae and seven femora suffering from bowing due to Paget's disease have been streightened operatively. In the tibiae, the deformities were of metaphysial genu varum with bowing in the sagittal plane of an average of 30 degrees combined with some medial rotation. In the femora, the main curve was anterolateral with some medial rotation and coxa vara. Seventeen cases united uneventfully after osteotomy. In three cases, there were septic complications, union occurred after removal of the internal fixation. Bowing recurred in three cases. The recurrence appeared to be related to incomplete correction leading to persistent mechanical strain on bones affected by rapid bone turnover. Inadequate internal fixation may also be a factor. All other cases were functionally improved by correction. Oblique osteotomy is indicated for the correction of tibial deformity when there is moderate medial rotation. Transverse osteotomy with fixation by intramedullary nailing is indicated for correction of femoral deformities."} {"id": "PMID:154145", "title": "[Severe strains of the cervical spine operated on by a posterior approach (author's transl)].", "content": "The authors have operated on 18 cases of severe strain of the cervical spine (six cases of C1-C2 and 12 cases of level cervical spine). They point out the difficulty of an accurate diagnosis in emergency. They emphasize the importance of flexion-extension X-rays when conventional X-rays are not strictly normal. After an analysis of the results they suggest that recent cases should be treated by posterior grafting at the level of C1 and C2, posterior plating at lower levels. Old and irreducible cases should be treated by osteotomy and anterior grafting: banding with grafting at C1 and C2, posterior screwed plating at the inferior cervical level.", "contents": "[Severe strains of the cervical spine operated on by a posterior approach (author's transl)]. The authors have operated on 18 cases of severe strain of the cervical spine (six cases of C1-C2 and 12 cases of level cervical spine). They point out the difficulty of an accurate diagnosis in emergency. They emphasize the importance of flexion-extension X-rays when conventional X-rays are not strictly normal. After an analysis of the results they suggest that recent cases should be treated by posterior grafting at the level of C1 and C2, posterior plating at lower levels. Old and irreducible cases should be treated by osteotomy and anterior grafting: banding with grafting at C1 and C2, posterior screwed plating at the inferior cervical level."} {"id": "PMID:154146", "title": "[Surgical treatment of stiff knee following femoral sepsis and septic arthritis of the knee (author's transl)].", "content": "The authors have studied the results of attempts to restore joint movement in stiff knees after septic non-union of fractures of the femoral shaft or after septic arthritis of the knee by arthrolysis and quadriceps release. Fifteen procedures were done on fourteen patients with severe limitation of movements. The results were gratifying; eight very good and four good. No case was made worse. The technique is described in detail and operative and post-operative complications described. A long-term follow-up study showed that the results tended to improve after several years. The prognosis can be based on the degree of flexion obtained during operation, though free flexion should be distinguished from forced flexion. It is concluded that the procedures used are worthwhile in spite of previous sepsis.", "contents": "[Surgical treatment of stiff knee following femoral sepsis and septic arthritis of the knee (author's transl)]. The authors have studied the results of attempts to restore joint movement in stiff knees after septic non-union of fractures of the femoral shaft or after septic arthritis of the knee by arthrolysis and quadriceps release. Fifteen procedures were done on fourteen patients with severe limitation of movements. The results were gratifying; eight very good and four good. No case was made worse. The technique is described in detail and operative and post-operative complications described. A long-term follow-up study showed that the results tended to improve after several years. The prognosis can be based on the degree of flexion obtained during operation, though free flexion should be distinguished from forced flexion. It is concluded that the procedures used are worthwhile in spite of previous sepsis."} {"id": "PMID:154150", "title": "[Flexor tendon grafting. The use of a modified Hunter's technique (author's transl)].", "content": "The authors describe a modification of Hunter's technique of flexor tendon grafting. The operation is performed in two stages. At the first stage, a silastic prosthesis is inserted and the proximal end of the flexor digitorum profundus is sutured to the tendon of palmaris longus. This suture will represent the proximal suture of the future graft. At the second stage, six weeks later, the palmaris longus is divided proximally and the graft is passed distally to be sutured to the terminal phalanx. This modified technique allows a gain in time, a better blood supply to the graft and a safer proximal suture.", "contents": "[Flexor tendon grafting. The use of a modified Hunter's technique (author's transl)]. The authors describe a modification of Hunter's technique of flexor tendon grafting. The operation is performed in two stages. At the first stage, a silastic prosthesis is inserted and the proximal end of the flexor digitorum profundus is sutured to the tendon of palmaris longus. This suture will represent the proximal suture of the future graft. At the second stage, six weeks later, the palmaris longus is divided proximally and the graft is passed distally to be sutured to the terminal phalanx. This modified technique allows a gain in time, a better blood supply to the graft and a safer proximal suture."} {"id": "PMID:154157", "title": "[Induction of experimental diabetes in frog (author's transl)].", "content": "The effect of diabetogenic agents, alloxan and streptozotocin, in frogs has been studied. These drugs were administered to the animals by injection into the dorsal lymph sac. Alloxan did not exert any effect at non-lethal doses. At 300 mg/kg alloxan caused death of most of the animals in an hyperglycemic state in less than 72 hours. Streptozotocin at doses lower than 1 g/kg was ineffective. At 1.5 g/kg, a non-lethal dose, about half of the animals became diabetic.", "contents": "[Induction of experimental diabetes in frog (author's transl)]. The effect of diabetogenic agents, alloxan and streptozotocin, in frogs has been studied. These drugs were administered to the animals by injection into the dorsal lymph sac. Alloxan did not exert any effect at non-lethal doses. At 300 mg/kg alloxan caused death of most of the animals in an hyperglycemic state in less than 72 hours. Streptozotocin at doses lower than 1 g/kg was ineffective. At 1.5 g/kg, a non-lethal dose, about half of the animals became diabetic."} {"id": "PMID:154158", "title": "Reversible modification of rat liver F1-ATPase by a redox reaction.", "content": "F1-ATPase from rat liver mitochondria exhibited a change in properties when reduced by dithionite: an increase in activity together with a disappearance of its sensitivity to bicarbonate stimulation was observed. A complete reversion to the original properties was achieved with the oxidizing agent 2,6-dichlorophenolindophenol.", "contents": "Reversible modification of rat liver F1-ATPase by a redox reaction. F1-ATPase from rat liver mitochondria exhibited a change in properties when reduced by dithionite: an increase in activity together with a disappearance of its sensitivity to bicarbonate stimulation was observed. A complete reversion to the original properties was achieved with the oxidizing agent 2,6-dichlorophenolindophenol."} {"id": "PMID:154159", "title": "Rat liver mitochondrial F1-ATPase, an FAD containing ferroprotein.", "content": "F1-ATPase isolated from rat liver mitochondria has been found to contain approximately 1 mole of FAD and 6 g atoms of nonheme iron per mole of enzyme.", "contents": "Rat liver mitochondrial F1-ATPase, an FAD containing ferroprotein. F1-ATPase isolated from rat liver mitochondria has been found to contain approximately 1 mole of FAD and 6 g atoms of nonheme iron per mole of enzyme."} {"id": "PMID:154155", "title": "[Visceral larva migrans].", "content": "The clinical records of patients with visceral larva migrans confirmed through laparoscopy and other tests are reviewed. This review was prompted by the admittance of two patients with this affection in the last years. Medical literature was reviewed, and conclusions are made.", "contents": "[Visceral larva migrans]. The clinical records of patients with visceral larva migrans confirmed through laparoscopy and other tests are reviewed. This review was prompted by the admittance of two patients with this affection in the last years. Medical literature was reviewed, and conclusions are made."} {"id": "PMID:154160", "title": "ATPase, an electron carrier and energy transducer: the missing link in oxidative phosphorylation?", "content": "A mechanism for oxidative phosphorylation is proposed. ATP synthesis would take place on a catalytic site of ATPase constituted by two irons with ligands ATP, ADP, and Pi. The interchange of ATP with ADP and Pi makes possible a redox cycle between two potentials permitting the energy transduction.", "contents": "ATPase, an electron carrier and energy transducer: the missing link in oxidative phosphorylation? A mechanism for oxidative phosphorylation is proposed. ATP synthesis would take place on a catalytic site of ATPase constituted by two irons with ligands ATP, ADP, and Pi. The interchange of ATP with ADP and Pi makes possible a redox cycle between two potentials permitting the energy transduction."} {"id": "PMID:154164", "title": "Intranasal ipratropium: inhibition of methacholine induced hypersecretion.", "content": "The submucous glands of the nose have an abundant innervation from the parasympathetic nervous system, and rhinorrhea, a symptom of perennial rhinitis, is in all probability caused by an increased activity in these nerves. Pharmacological blockade with atropine-like compounds will therefore be a logical method of treatment. Rhinorrhoea was brought about in the laboratory in 15 healthy experimental subjects by the intranasal application of methacholine. The experimental subjects were pretreated with Ipratropium (Atrovent, Boehringer-Ingelheim) or placebo in a double-blind trial and it was found that Atrovent could effectively inhibit the methacholine induced hypersecretion for up to 6 hours, without local or systemic side-effects. The methacholine induced hypersecretion could also be effectively blocked in 10 patients with perennial rhinitis, and an open clinical study demonstrated that Atrovent had an effect on the spontaneous rhinorrhoea of these patients.", "contents": "Intranasal ipratropium: inhibition of methacholine induced hypersecretion. The submucous glands of the nose have an abundant innervation from the parasympathetic nervous system, and rhinorrhea, a symptom of perennial rhinitis, is in all probability caused by an increased activity in these nerves. Pharmacological blockade with atropine-like compounds will therefore be a logical method of treatment. Rhinorrhoea was brought about in the laboratory in 15 healthy experimental subjects by the intranasal application of methacholine. The experimental subjects were pretreated with Ipratropium (Atrovent, Boehringer-Ingelheim) or placebo in a double-blind trial and it was found that Atrovent could effectively inhibit the methacholine induced hypersecretion for up to 6 hours, without local or systemic side-effects. The methacholine induced hypersecretion could also be effectively blocked in 10 patients with perennial rhinitis, and an open clinical study demonstrated that Atrovent had an effect on the spontaneous rhinorrhoea of these patients."} {"id": "PMID:154169", "title": "Successful kidney transplantation in a man with Dacron \"trouser\" prosthesis.", "content": "The case history of a male patient, 62 years old, in preterminal uremia at transplantation with a cadaveric kidney is described. Twelve years before the transplantation he was operated on because of an aortic aneurysm where the abdominal aorta and both iliac arteries were substituted with a Dacron prosthesis. The kidney was anastomosed to this vessel substitute and functioned excellently for more than five years and the patient was completely rehabilitated.", "contents": "Successful kidney transplantation in a man with Dacron \"trouser\" prosthesis. The case history of a male patient, 62 years old, in preterminal uremia at transplantation with a cadaveric kidney is described. Twelve years before the transplantation he was operated on because of an aortic aneurysm where the abdominal aorta and both iliac arteries were substituted with a Dacron prosthesis. The kidney was anastomosed to this vessel substitute and functioned excellently for more than five years and the patient was completely rehabilitated."} {"id": "PMID:154170", "title": "Persisting hypertension after renal artery reconstruction. A follow-up study.", "content": "Twenty-four patients with persisting hypertension after renal artery reconstruction were re-investigated 1--8 years after surgery. They underwent renal arteriography, determination of plasma renin activity, renography and renal function studies in order to find the causes of the postoperative hypertension. Restenosis was found in 6 patients, in 3 of whom it was of functional significance according to the positive renin tests (renin ratio greater than 1.5). Positive renin tests were found in 2 other patients. One had occlusion of a renal artery branch and the other hypoplasia of the kidney due to chronic nephritis. No explanation of the persisting hypertension could be found in 19 patients at re-examination. In 10 of them, however, biopsy from the affected kidney obtained during operation showed nephrosclerosis, which may explain the outcome. Fourteen of the 19 patients had negative renin tests preoperatively. These negative tests indicate that renal artery stenosis was not the only cause of hypertension. It may be concluded that the renin test is of the utmost value in the selection of patients for renal artery reconstruction and should always be considered. A biopsy from the contralateral kidney may be necessary in order to detect other causes of hypertension than renal artery stenosis. The importance of re-investigating patients with persisting hypertension is confirmed by the present study.", "contents": "Persisting hypertension after renal artery reconstruction. A follow-up study. Twenty-four patients with persisting hypertension after renal artery reconstruction were re-investigated 1--8 years after surgery. They underwent renal arteriography, determination of plasma renin activity, renography and renal function studies in order to find the causes of the postoperative hypertension. Restenosis was found in 6 patients, in 3 of whom it was of functional significance according to the positive renin tests (renin ratio greater than 1.5). Positive renin tests were found in 2 other patients. One had occlusion of a renal artery branch and the other hypoplasia of the kidney due to chronic nephritis. No explanation of the persisting hypertension could be found in 19 patients at re-examination. In 10 of them, however, biopsy from the affected kidney obtained during operation showed nephrosclerosis, which may explain the outcome. Fourteen of the 19 patients had negative renin tests preoperatively. These negative tests indicate that renal artery stenosis was not the only cause of hypertension. It may be concluded that the renin test is of the utmost value in the selection of patients for renal artery reconstruction and should always be considered. A biopsy from the contralateral kidney may be necessary in order to detect other causes of hypertension than renal artery stenosis. The importance of re-investigating patients with persisting hypertension is confirmed by the present study."} {"id": "PMID:154172", "title": "Antibiotic susceptibility of Neisseria gonorrhoeae isolated in Johannesburg.", "content": "The susceptibility of 175 clinical isolates of Neisseria gonorrhoeae to penicillin G, ampicillin, erythromycin, tetracycline and spectinomycin was determined. Almost one-fifth of strains were relatively resistant to penicillin G. Relative resistance to penicillin G was significantly correlated with resistance to ampicillin, tetracycline and erythromycin, but not with resistance to spectinomycin. No penicillinase-producing or spectinomycin-resistant strains were encountered in this study. The relevance of the findings to the management of gonococcal urethritis is discussed.", "contents": "Antibiotic susceptibility of Neisseria gonorrhoeae isolated in Johannesburg. The susceptibility of 175 clinical isolates of Neisseria gonorrhoeae to penicillin G, ampicillin, erythromycin, tetracycline and spectinomycin was determined. Almost one-fifth of strains were relatively resistant to penicillin G. Relative resistance to penicillin G was significantly correlated with resistance to ampicillin, tetracycline and erythromycin, but not with resistance to spectinomycin. No penicillinase-producing or spectinomycin-resistant strains were encountered in this study. The relevance of the findings to the management of gonococcal urethritis is discussed."} {"id": "PMID:154173", "title": "Six years' experience in a children's hospital genetic clinic.", "content": "A genetic clinic has been held once a week at the Red Cross War Memorial Children's Hospital for the past 6 years. During the period 1971--1977, 579 patients were seen, of whom 56% had genetic conditions due to chromosome defects, Mendelian traits or a multifactorial type of inheritance. In these, genetic counselling was a prime importance regarding prognosis, risk of recurrence and possibility of antenatal diagnosis. A further 25% of patients seen had conditions of non-genetic origin and could be reassured, while in the remaining 19% no specific causation was detected.", "contents": "Six years' experience in a children's hospital genetic clinic. A genetic clinic has been held once a week at the Red Cross War Memorial Children's Hospital for the past 6 years. During the period 1971--1977, 579 patients were seen, of whom 56% had genetic conditions due to chromosome defects, Mendelian traits or a multifactorial type of inheritance. In these, genetic counselling was a prime importance regarding prognosis, risk of recurrence and possibility of antenatal diagnosis. A further 25% of patients seen had conditions of non-genetic origin and could be reassured, while in the remaining 19% no specific causation was detected."} {"id": "PMID:154174", "title": "Huntington's chorea in a black Rhodesian family.", "content": "Clinical features suggesting a diagnosis of Huntington's chorea in several siblings in a Black Rhodesian family are described. A progressive and eventually fatal mental deterioration accompanied by gradually worsening choreiform movements has until the present time occurred in only a single generation of this family, which precludes a definitive diagnosis based on the triad of family history, chorea and dementia. It is suggested that Huntington's chorea is the most likely diagnosis.", "contents": "Huntington's chorea in a black Rhodesian family. Clinical features suggesting a diagnosis of Huntington's chorea in several siblings in a Black Rhodesian family are described. A progressive and eventually fatal mental deterioration accompanied by gradually worsening choreiform movements has until the present time occurred in only a single generation of this family, which precludes a definitive diagnosis based on the triad of family history, chorea and dementia. It is suggested that Huntington's chorea is the most likely diagnosis."} {"id": "PMID:154176", "title": "A new surgical procedure for the treatment of gastroesophageal reflux and hiatal hernia.", "content": "A procedure for the treatment of sliding esophageal hiatal hernia and gastroesophageal reflux has been successfully and safely performed upon 46 patients. It is based on the placement of a ringlike silicone prosthesis around the lower part of the esophagus, below the diaphragm.", "contents": "A new surgical procedure for the treatment of gastroesophageal reflux and hiatal hernia. A procedure for the treatment of sliding esophageal hiatal hernia and gastroesophageal reflux has been successfully and safely performed upon 46 patients. It is based on the placement of a ringlike silicone prosthesis around the lower part of the esophagus, below the diaphragm."} {"id": "PMID:154177", "title": "Management of superior gluteal artery aneurysm by percutaneous balloon catheter occlusion: a case report.", "content": "A 19-year-old woman developed an aneurysm of the left superior gluteal artery following laparoscopy. Percutaneous insertion of a balloon catheter into the neck of the aneurysm for 48 hours resulted in permanent thrombosis of the aneurysm. Use of balloon catheters in the management of surgically inaccessible vascular lesions in discussed.", "contents": "Management of superior gluteal artery aneurysm by percutaneous balloon catheter occlusion: a case report. A 19-year-old woman developed an aneurysm of the left superior gluteal artery following laparoscopy. Percutaneous insertion of a balloon catheter into the neck of the aneurysm for 48 hours resulted in permanent thrombosis of the aneurysm. Use of balloon catheters in the management of surgically inaccessible vascular lesions in discussed."} {"id": "PMID:154175", "title": "Spectinomycin in the treatment of anal gonorrhea: a retrospective study.", "content": "The authors conducted a retrospective study of 125 male patients treated for anal gonorrhea with 4 g of spectinomycin in a social hygiene clinic. Of those treated, nine (7.2%) still had cultures positive for Neisseria gonorrhoeae when tested again five to 14 days after treatment.", "contents": "Spectinomycin in the treatment of anal gonorrhea: a retrospective study. The authors conducted a retrospective study of 125 male patients treated for anal gonorrhea with 4 g of spectinomycin in a social hygiene clinic. Of those treated, nine (7.2%) still had cultures positive for Neisseria gonorrhoeae when tested again five to 14 days after treatment."} {"id": "PMID:154194", "title": "[Bacterial skin infections in the dog (author's transl)].", "content": "The most common bacterial skin conditions in dogs are reviewed in the present paper. An introductory part on the pathogenesis of pyoderma and some universal morphological dermatological concepts is followed by a systematic study of superficial and deep forms of pyoderma. In addition to the bacterial diagnosis, the results of bacteriological examination of fifty-three dogs with pyoderma submitted to the University Clinic of small animal medicine are reported. Moreover, a guide to the institution of adequate therapy is suggested.", "contents": "[Bacterial skin infections in the dog (author's transl)]. The most common bacterial skin conditions in dogs are reviewed in the present paper. An introductory part on the pathogenesis of pyoderma and some universal morphological dermatological concepts is followed by a systematic study of superficial and deep forms of pyoderma. In addition to the bacterial diagnosis, the results of bacteriological examination of fifty-three dogs with pyoderma submitted to the University Clinic of small animal medicine are reported. Moreover, a guide to the institution of adequate therapy is suggested."} {"id": "PMID:154195", "title": "Anomalous mixed lymphocyte culture reactivity between HLA--A, --B, --C, --DR identical siblings.", "content": "Complete HLA typing including HLA--A, --B, --C, --DR (D related B cell typing), --D, mixed lymphocyte culture (MLC), and primed lymphocyte testing (PLT), together with complete red blood cell (RBC), glyoxalase (GLO), GBG (Factor B), and phosphoglucomutase 3 (PGM3) typings were performed on a informative family. The five siblings inherited the four possible combinations of parental HLA haplotypes, and two of the siblings were HLA--A, --B, --C and --DR identical. Repeated MLC testing of the family revealed positive mixed lymphocyte reactivity in all combinations. B cell typing for the DR specificities demonstrated no variation from the expected inheritance pattern and specifically no recombination event. GBG and GLO typings militated against a recombination involving the paternal chromosome. HLA--D testing revealed that only one of the HLA--A, --B, --C, and --DR identical siblings gave typing responses to the HLA--Dw3 specificity present on that maternal haplotype. Utilizing HLA haploidentical combinations, lymphocytes were primed against the four parental haplotypes and the non-Dw3 haplotype of interest (Aw24--B8--DRw3--LDY) in the PLT. The sibling inheriting this haplo-type did not restimulate cells primed against the A2--B40--DRW6--LDY specificity. Furthermore, no discrimination was observed in the restimulation of lymphocytes primed against this haplo-type. Possible interpretations of these family data include: a spontaneous mutation, non-major histocompatibility locus (MHC) stimulation, and HLA--DR/D recombination.", "contents": "Anomalous mixed lymphocyte culture reactivity between HLA--A, --B, --C, --DR identical siblings. Complete HLA typing including HLA--A, --B, --C, --DR (D related B cell typing), --D, mixed lymphocyte culture (MLC), and primed lymphocyte testing (PLT), together with complete red blood cell (RBC), glyoxalase (GLO), GBG (Factor B), and phosphoglucomutase 3 (PGM3) typings were performed on a informative family. The five siblings inherited the four possible combinations of parental HLA haplotypes, and two of the siblings were HLA--A, --B, --C and --DR identical. Repeated MLC testing of the family revealed positive mixed lymphocyte reactivity in all combinations. B cell typing for the DR specificities demonstrated no variation from the expected inheritance pattern and specifically no recombination event. GBG and GLO typings militated against a recombination involving the paternal chromosome. HLA--D testing revealed that only one of the HLA--A, --B, --C, and --DR identical siblings gave typing responses to the HLA--Dw3 specificity present on that maternal haplotype. Utilizing HLA haploidentical combinations, lymphocytes were primed against the four parental haplotypes and the non-Dw3 haplotype of interest (Aw24--B8--DRw3--LDY) in the PLT. The sibling inheriting this haplo-type did not restimulate cells primed against the A2--B40--DRW6--LDY specificity. Furthermore, no discrimination was observed in the restimulation of lymphocytes primed against this haplo-type. Possible interpretations of these family data include: a spontaneous mutation, non-major histocompatibility locus (MHC) stimulation, and HLA--DR/D recombination."} {"id": "PMID:154196", "title": "HLA--Dw4 and rheumatoid arthritis.", "content": "Forty-seven patients with a \"definite\" or \"classical\" rheumatoid arthritis according to the ARA criteria were typed for the serologically detectable HLA--A, --B, and --C antigens and 36 of these patients were typed for the HLA--D antigens, Dw1, 2, 3, 4, 6, 7, and 8 by the MLC technique. The frequency of Dw4 was increased to 44.4% in the patients compared to 17.2% in normal controls (P = 8 X 10(-4)). The frequency of Dw1 and Dw7 was also increased although this was only of borderline significance. The frequency of Dw2 was remarkably low, especially in females, which is of interest, as the same antigen has a low frequency in some other autoimmune diseases. No significant deviations of the frequencies of HLA--A, --B, and --C antigens were found in rheumatoid arthritis patients.", "contents": "HLA--Dw4 and rheumatoid arthritis. Forty-seven patients with a \"definite\" or \"classical\" rheumatoid arthritis according to the ARA criteria were typed for the serologically detectable HLA--A, --B, and --C antigens and 36 of these patients were typed for the HLA--D antigens, Dw1, 2, 3, 4, 6, 7, and 8 by the MLC technique. The frequency of Dw4 was increased to 44.4% in the patients compared to 17.2% in normal controls (P = 8 X 10(-4)). The frequency of Dw1 and Dw7 was also increased although this was only of borderline significance. The frequency of Dw2 was remarkably low, especially in females, which is of interest, as the same antigen has a low frequency in some other autoimmune diseases. No significant deviations of the frequencies of HLA--A, --B, and --C antigens were found in rheumatoid arthritis patients."} {"id": "PMID:154199", "title": "[Local nicotinamide therapy in erosive lichen of the oral mucosa].", "content": "The local treatment of erosive lichen planus by means of subfocal injections of nicotinamide has been successful in 19 of 25 cases. Nevertheless, it is no true alternative of the systemic chloroquine-triamcinolone treatment. A therapeutical program is presented in which the more riskful use of corticosteroids and chloroquine ranks but second.", "contents": "[Local nicotinamide therapy in erosive lichen of the oral mucosa]. The local treatment of erosive lichen planus by means of subfocal injections of nicotinamide has been successful in 19 of 25 cases. Nevertheless, it is no true alternative of the systemic chloroquine-triamcinolone treatment. A therapeutical program is presented in which the more riskful use of corticosteroids and chloroquine ranks but second."} {"id": "PMID:154201", "title": "Followup of abdominal neourethra.", "content": "Abdominal neourethrostomy is a highly satisfactory form of urinary diversion for patients with irreparable urethral stricture or destruction. Normal renal function, structure and urinary continence have been observed in 7 patients for as long as 17 years.", "contents": "Followup of abdominal neourethra. Abdominal neourethrostomy is a highly satisfactory form of urinary diversion for patients with irreparable urethral stricture or destruction. Normal renal function, structure and urinary continence have been observed in 7 patients for as long as 17 years."} {"id": "PMID:154207", "title": "Follow-up study of patients with cerebral palsy.", "content": "Of 319 patients with cerebral palsy recalled for reevaluation 15 years after the initial visit, 10 percent had died. Of the living, 55 percent had spasticity, 32 percent had athetosis, 4 percent had ataxia and 9 percent had mixed spasticity and athetosis; 38 percent had an intelligence quotient (IQ) less than 50, 24 percent between 50 and 79, and 38 percent had IQ above 80. There was a high correlation between overall functional outcome and intellectual level. Severity of physical disability, as measured by hand use, mobility and speech, also correlated with dependence, in part because increased severity of the disability was associated with decreased intellectual capacity generally.Twenty-five years after the initial visit, parental attitudes and personality intactness were evaluated (using the Minnesota Multiphasic Personality Inventory [MMPI]) and were correlated with satisfaction with status in life in 28 persons predicted to be independent on the 15-year study. Twenty (72 percent) of the 28 were satisfied with their status in life and of these, 16 were evaluated (with the MMPI) with 70 percent scoring in the normal range; 13 (65 percent) had parents with a positive attitude. Positive attitude was defined as parental feelings that the handicapped child was a worthy, valuable person, to be encouraged and assisted but not isolated from the world of nonhandicapped people. Careful serial assessment by professional teams combined with repeated long-term counseling of families can result in optimal outcome for the disability level involved, due to the primary role parents play in the development of a child's character and behavior.", "contents": "Follow-up study of patients with cerebral palsy. Of 319 patients with cerebral palsy recalled for reevaluation 15 years after the initial visit, 10 percent had died. Of the living, 55 percent had spasticity, 32 percent had athetosis, 4 percent had ataxia and 9 percent had mixed spasticity and athetosis; 38 percent had an intelligence quotient (IQ) less than 50, 24 percent between 50 and 79, and 38 percent had IQ above 80. There was a high correlation between overall functional outcome and intellectual level. Severity of physical disability, as measured by hand use, mobility and speech, also correlated with dependence, in part because increased severity of the disability was associated with decreased intellectual capacity generally.Twenty-five years after the initial visit, parental attitudes and personality intactness were evaluated (using the Minnesota Multiphasic Personality Inventory [MMPI]) and were correlated with satisfaction with status in life in 28 persons predicted to be independent on the 15-year study. Twenty (72 percent) of the 28 were satisfied with their status in life and of these, 16 were evaluated (with the MMPI) with 70 percent scoring in the normal range; 13 (65 percent) had parents with a positive attitude. Positive attitude was defined as parental feelings that the handicapped child was a worthy, valuable person, to be encouraged and assisted but not isolated from the world of nonhandicapped people. Careful serial assessment by professional teams combined with repeated long-term counseling of families can result in optimal outcome for the disability level involved, due to the primary role parents play in the development of a child's character and behavior."} {"id": "PMID:154209", "title": "[Cholestatic jaundice and hypophosphataemia in parenterally-fed premature infants--coincidence or causal connection? (author's transl)].", "content": "A report is presented of the chemical pathological findings in 14 premature and one full-term infant receiving almost exclusively parenteral nutrition during the first two weeks of life. Six infants developed cholestatic jaundice. The underlying diseases were the idiopathic respiratory distress syndrome in 10, gastroschisis in 3 and renal insufficiency in 1, while one was an otherwise healthy small for dates infant. After parenteral nutrition had been discontinued obstructive jaundice cleared by the third month of life except in one infant. Apart from the higher glucose intake during the second week, jaundiced infants principally differed from non-jaundiced infants by the development of significant hypophosphataemia. An attempt was made to correlate aetiologically the presence of cholestatic jaundice with the finding of hypophosphataemia on the possible basis of a disturbance of energy metabolism.", "contents": "[Cholestatic jaundice and hypophosphataemia in parenterally-fed premature infants--coincidence or causal connection? (author's transl)]. A report is presented of the chemical pathological findings in 14 premature and one full-term infant receiving almost exclusively parenteral nutrition during the first two weeks of life. Six infants developed cholestatic jaundice. The underlying diseases were the idiopathic respiratory distress syndrome in 10, gastroschisis in 3 and renal insufficiency in 1, while one was an otherwise healthy small for dates infant. After parenteral nutrition had been discontinued obstructive jaundice cleared by the third month of life except in one infant. Apart from the higher glucose intake during the second week, jaundiced infants principally differed from non-jaundiced infants by the development of significant hypophosphataemia. An attempt was made to correlate aetiologically the presence of cholestatic jaundice with the finding of hypophosphataemia on the possible basis of a disturbance of energy metabolism."} {"id": "PMID:154210", "title": "[Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)].", "content": "Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed.", "contents": "[Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)]. Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed."} {"id": "PMID:154216", "title": "[Long-term cultures of trophoblast cells and mixed trophoblast cultures as a model for in-vitro studies (author's transl)].", "content": "Trophoblast cell-cultures provide a much promising model for qualitative and quantitative in-vitro-examinations of immunological, morphological and biochemical items. In the present paper an attempt has been made to analyze the light-microscopically identificable morphological modifications of the cultured cells under standardized culture-conditions in a temporary order. Furthermore, a number of single cases is presented in which mixed cultures of trophoblast cells with heterologous cells of embryonic origin and with cells derived from adult malignoma were tried.", "contents": "[Long-term cultures of trophoblast cells and mixed trophoblast cultures as a model for in-vitro studies (author's transl)]. Trophoblast cell-cultures provide a much promising model for qualitative and quantitative in-vitro-examinations of immunological, morphological and biochemical items. In the present paper an attempt has been made to analyze the light-microscopically identificable morphological modifications of the cultured cells under standardized culture-conditions in a temporary order. Furthermore, a number of single cases is presented in which mixed cultures of trophoblast cells with heterologous cells of embryonic origin and with cells derived from adult malignoma were tried."} {"id": "PMID:154217", "title": "Mode of binding of pyridoxal phosphate to 5-aminolevulinate synthase.", "content": "5-Aminolevulinate synthase of Rhodopseudomonas spheroides interacts with its cofactor, pyridoxal phosphate, and shows an absorption maximum at 430 nm with a probable shoulder at 320--330 nm. The enzyme-PLP complex absorbing at 430 nm is the predominant species at pH 7.2 and can be reduced by NaBH4 at neutral pH with a spectral shift of the absorption maximum to 325 nm. These data suggests the formation of a Schiff base rather than a substituted aldimine between the enzyme and pyridoxal phosphate. The decrease in absorption at 430 nm and increase in absorption at 325 nm by the addition of 2-mercaptoethanol seem to support Schiff base structures for the absorption bands at 430 nm and 320--330 nm. Both pyridoxal phosphate and glycine can equally protect the enzyme from inactivation by sulfhydryl reagents. The inhibition by p-chloromercuribenzoate versus PLP and glycine is noncompetitive and that by N-ethylmaleimide is noncompetitive with glycine and competitive with PLP. These results suggest either a conformational change in the presence of substrates or loss of affinity by the enzyme for PLP, rather than an interaction of PLP with a -SH group of the enzyme. The combined data seems to eliminate the possibility of the formation of a thiohemiacetal or a substituted aldimine and support rather strongly the formation of a Schiff base between the enzyme and pyridoxal phosphate.", "contents": "Mode of binding of pyridoxal phosphate to 5-aminolevulinate synthase. 5-Aminolevulinate synthase of Rhodopseudomonas spheroides interacts with its cofactor, pyridoxal phosphate, and shows an absorption maximum at 430 nm with a probable shoulder at 320--330 nm. The enzyme-PLP complex absorbing at 430 nm is the predominant species at pH 7.2 and can be reduced by NaBH4 at neutral pH with a spectral shift of the absorption maximum to 325 nm. These data suggests the formation of a Schiff base rather than a substituted aldimine between the enzyme and pyridoxal phosphate. The decrease in absorption at 430 nm and increase in absorption at 325 nm by the addition of 2-mercaptoethanol seem to support Schiff base structures for the absorption bands at 430 nm and 320--330 nm. Both pyridoxal phosphate and glycine can equally protect the enzyme from inactivation by sulfhydryl reagents. The inhibition by p-chloromercuribenzoate versus PLP and glycine is noncompetitive and that by N-ethylmaleimide is noncompetitive with glycine and competitive with PLP. These results suggest either a conformational change in the presence of substrates or loss of affinity by the enzyme for PLP, rather than an interaction of PLP with a -SH group of the enzyme. The combined data seems to eliminate the possibility of the formation of a thiohemiacetal or a substituted aldimine and support rather strongly the formation of a Schiff base between the enzyme and pyridoxal phosphate."} {"id": "PMID:154218", "title": "Uracil catabolism by Escherichia coli K12S.", "content": "Experiments designed to elucidate the mechanism of uracil degradation by E. coli K12S showed that in contrast to uracil, dihydrouracil--the postulated intermediate of a reductive mechanism--did not stimulate the growth of bacteria as additional source of nitrogen, nor it was catabolized to ureido carbon dioxide. However, the chromatographic analysis of dihydrouracil metabolic products, revealed the presence of an enzyme converting dihydrouracil to beta-ureidopropionic acid. Results of growth and biochemical studies indicated that barbituric acid--the postulated intermediate of an oxidative pathway--is not involved in uracil degradation.", "contents": "Uracil catabolism by Escherichia coli K12S. Experiments designed to elucidate the mechanism of uracil degradation by E. coli K12S showed that in contrast to uracil, dihydrouracil--the postulated intermediate of a reductive mechanism--did not stimulate the growth of bacteria as additional source of nitrogen, nor it was catabolized to ureido carbon dioxide. However, the chromatographic analysis of dihydrouracil metabolic products, revealed the presence of an enzyme converting dihydrouracil to beta-ureidopropionic acid. Results of growth and biochemical studies indicated that barbituric acid--the postulated intermediate of an oxidative pathway--is not involved in uracil degradation."} {"id": "PMID:154219", "title": "The kinetics of formation of metarhodopsin in intact photoreceptors of the fly.", "content": "The formation of metarhodopsin in fly photoreceptor no. 1--6 occurs at room temperature with a time constant of 125 microseconds (Q10 approximately 2.5). The formation of rhodopsin is faster by factor of 1/10 to 1/100 at least.", "contents": "The kinetics of formation of metarhodopsin in intact photoreceptors of the fly. The formation of metarhodopsin in fly photoreceptor no. 1--6 occurs at room temperature with a time constant of 125 microseconds (Q10 approximately 2.5). The formation of rhodopsin is faster by factor of 1/10 to 1/100 at least."} {"id": "PMID:154220", "title": "[Antibiotics from basidiomycetes, VI. Merulinic acids A, B, and C, new antibiotics from Merulius tremellosus and Phlebia radiata (author's transl)].", "content": "Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A.", "contents": "[Antibiotics from basidiomycetes, VI. Merulinic acids A, B, and C, new antibiotics from Merulius tremellosus and Phlebia radiata (author's transl)]. Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A."} {"id": "PMID:154222", "title": "Influence of ions and chelating agents on the haemolymphacetylcholinesterase of Mytilus edulis.", "content": "By use of different inhibitors as well as atomic absorption spectrophotometry it has been shown that the haemolymph-acetylcholinesterase (E. c. 3.1.1.7) of the sea mussel Mytilus edulis is a metalloprotein containing 2,95 Fe2+-ions per subunit. All inhibitors used (1,10-phenanthroline, salicylic aldehyde, 2,2'-dipyridyl, 8-hydroxyquinoline) showed a non-competitive inhibition, which was not pH-dependent. Some divalent cations caused a marked increase of the enzyme activity, some heavy metals inhibited the enzyme almost completely; monovalent inorganic cations did not influence the enzyme at all. Besides NaF and Na2SiF6, which showed a non-competitive inhibition comparable to the inhibition observed with the chelating agents, and NaN3, whose mode of action was not identifiable, no inhibition by different mono- and divalent inorganic anions was to be observed. Ammonium ions caused no enzyme inhibition, but length the inhibition power of substituted ammonium ions increased with an increasing C-chain. The influence of some organic solvents on the enzyme activity is demonstrated.", "contents": "Influence of ions and chelating agents on the haemolymphacetylcholinesterase of Mytilus edulis. By use of different inhibitors as well as atomic absorption spectrophotometry it has been shown that the haemolymph-acetylcholinesterase (E. c. 3.1.1.7) of the sea mussel Mytilus edulis is a metalloprotein containing 2,95 Fe2+-ions per subunit. All inhibitors used (1,10-phenanthroline, salicylic aldehyde, 2,2'-dipyridyl, 8-hydroxyquinoline) showed a non-competitive inhibition, which was not pH-dependent. Some divalent cations caused a marked increase of the enzyme activity, some heavy metals inhibited the enzyme almost completely; monovalent inorganic cations did not influence the enzyme at all. Besides NaF and Na2SiF6, which showed a non-competitive inhibition comparable to the inhibition observed with the chelating agents, and NaN3, whose mode of action was not identifiable, no inhibition by different mono- and divalent inorganic anions was to be observed. Ammonium ions caused no enzyme inhibition, but length the inhibition power of substituted ammonium ions increased with an increasing C-chain. The influence of some organic solvents on the enzyme activity is demonstrated."} {"id": "PMID:154223", "title": "Differentiation of Rhizobium japonicum, III. Inhibition of nitrogenase derepression by chloramphenicol and rifampicin concentrations, not inhibiting growth.", "content": "Development of nitrogenase (40--140 nmol C2H4.mg protein-1.h-1) in Rhizobium japonicum 61-A-101 after transfer to special culture conditions (medium 20 P, 2% O2, 10% CO2, 88% N2 in the gas phase) is inhibited by chloramphenicol (6 X 10(-4)--10(-3) M) and by rifampicin (10(-5) M). These concentrations do not inhibit the slow growth of the cells under these conditions with a doubling time of the cell protein and living cell number of 3--5 d. Nitrogenase activity of previously derepressed cells is not inhibited by chloramphenicol. Growth of the cells under air in yeast extract-mannitol-glycerol medium (8 h doubling time) is affected significantly more by chloramphenicol (2.5 X 10(-4) M) than growth under nitrogenase derepressed culture conditions.", "contents": "Differentiation of Rhizobium japonicum, III. Inhibition of nitrogenase derepression by chloramphenicol and rifampicin concentrations, not inhibiting growth. Development of nitrogenase (40--140 nmol C2H4.mg protein-1.h-1) in Rhizobium japonicum 61-A-101 after transfer to special culture conditions (medium 20 P, 2% O2, 10% CO2, 88% N2 in the gas phase) is inhibited by chloramphenicol (6 X 10(-4)--10(-3) M) and by rifampicin (10(-5) M). These concentrations do not inhibit the slow growth of the cells under these conditions with a doubling time of the cell protein and living cell number of 3--5 d. Nitrogenase activity of previously derepressed cells is not inhibited by chloramphenicol. Growth of the cells under air in yeast extract-mannitol-glycerol medium (8 h doubling time) is affected significantly more by chloramphenicol (2.5 X 10(-4) M) than growth under nitrogenase derepressed culture conditions."} {"id": "PMID:154224", "title": "1H-NMR investigations on the hydrogen bond formation between the tranquilizers diazepam and nitrazepam and some nucleobases.", "content": "The formation of hydrogen bonds between the minor tranquilizers diazepam and nitrazepam and a few nucleobases was studied in deuterochloroform solution by means of proton magnetic resonance spectroscopy. The thermodynamic and spectroscopic data of the associations were evaluated on the basis of a dimer model, using the concentration dependent shifts of the protons involved in hydrogen bonds. The interactions of nitrazepam (deltaH0=-10 to -21 kJ/mol; deltaG025 -0.2 to -7.4 kJ/mol) were found to be stronger than those of diazepam (deltaH0=-10 to -13 kJ/mol; deltaG025=6.0 to 6.4 kJ/mol). The various binding sites of the benzodiazepines for hydrogen bonds are discussed.", "contents": "1H-NMR investigations on the hydrogen bond formation between the tranquilizers diazepam and nitrazepam and some nucleobases. The formation of hydrogen bonds between the minor tranquilizers diazepam and nitrazepam and a few nucleobases was studied in deuterochloroform solution by means of proton magnetic resonance spectroscopy. The thermodynamic and spectroscopic data of the associations were evaluated on the basis of a dimer model, using the concentration dependent shifts of the protons involved in hydrogen bonds. The interactions of nitrazepam (deltaH0=-10 to -21 kJ/mol; deltaG025 -0.2 to -7.4 kJ/mol) were found to be stronger than those of diazepam (deltaH0=-10 to -13 kJ/mol; deltaG025=6.0 to 6.4 kJ/mol). The various binding sites of the benzodiazepines for hydrogen bonds are discussed."} {"id": "PMID:154225", "title": "Structural aspects of histone complexes and nucleosomes revealed by the accessibility of cysteine side chains.", "content": "Chemical modification with 5,5'-dithiobis-(2-nitrobenzoic acid) shows that histone H3 cysteines 110 (chicken) or 96 and 110 (calf) are completely protected in native chromatin and core particles but become unmasked simultaneously during a salt induced dissociation. In whole histone extracted from chicken erythrocyte chromatin, H3 Cys-110 residues experience a uniform environment at 2 M NaCl and pH 5.5. In whole histone extracted under the same conditions from calf thymus, H3 Cys-96 provides a more accessible thiol group than Cys-110. At higher pH values a conformational heterogeneity is induced causing a partial exposure of both cysteine side chains. The kinetic approach described in the present work provides a highly sensitive means to probe the homogeneity of H3 containing protein complexes.", "contents": "Structural aspects of histone complexes and nucleosomes revealed by the accessibility of cysteine side chains. Chemical modification with 5,5'-dithiobis-(2-nitrobenzoic acid) shows that histone H3 cysteines 110 (chicken) or 96 and 110 (calf) are completely protected in native chromatin and core particles but become unmasked simultaneously during a salt induced dissociation. In whole histone extracted from chicken erythrocyte chromatin, H3 Cys-110 residues experience a uniform environment at 2 M NaCl and pH 5.5. In whole histone extracted under the same conditions from calf thymus, H3 Cys-96 provides a more accessible thiol group than Cys-110. At higher pH values a conformational heterogeneity is induced causing a partial exposure of both cysteine side chains. The kinetic approach described in the present work provides a highly sensitive means to probe the homogeneity of H3 containing protein complexes."} {"id": "PMID:154227", "title": "Calculation of the circular dichroism of Chironomus hemoglobin in the light of the quality of its X-ray structure.", "content": "For the larval hemoglobin III of the insect Chironomus thummi thummi, the rotational strength of the B (Soret) and Q band is calculated with a monopole/monopole and a dipole/dipole approximation applied to the atomic co-ordinates of the X-ray structures at 2.5 and 1.4 A resolution. In previous calculations using the 2.5 A co-ordinates and with perturbing groups being restricted to aromatic side-chains, the dipole/dipole approximation clearly confirmed the negative sign observed by experiment. The predominant interactions were those of phenylalanine residues. Recalculation with X-ray data refined to the present limits of performance corroborates the negativity of the rotational strength, but now the most important contributions are due to the peptide bonds formerly neglected. Also for the 2.5 A coordinates it is learned that in contrast to earlier expectation the influence of the backbone in this hemoglobin is rather strong. A substantial contribution is further obtained for the perturbation by one of the propionic acid carboxylate groups of the heme. Perspectives and problems of the approach are outlined.", "contents": "Calculation of the circular dichroism of Chironomus hemoglobin in the light of the quality of its X-ray structure. For the larval hemoglobin III of the insect Chironomus thummi thummi, the rotational strength of the B (Soret) and Q band is calculated with a monopole/monopole and a dipole/dipole approximation applied to the atomic co-ordinates of the X-ray structures at 2.5 and 1.4 A resolution. In previous calculations using the 2.5 A co-ordinates and with perturbing groups being restricted to aromatic side-chains, the dipole/dipole approximation clearly confirmed the negative sign observed by experiment. The predominant interactions were those of phenylalanine residues. Recalculation with X-ray data refined to the present limits of performance corroborates the negativity of the rotational strength, but now the most important contributions are due to the peptide bonds formerly neglected. Also for the 2.5 A coordinates it is learned that in contrast to earlier expectation the influence of the backbone in this hemoglobin is rather strong. A substantial contribution is further obtained for the perturbation by one of the propionic acid carboxylate groups of the heme. Perspectives and problems of the approach are outlined."} {"id": "PMID:154228", "title": "[Reactions of nascent quinones with methyl beta-alanate in glacial acetic acid and in aqueous solution (author's transl)].", "content": "In order to generate a model for the reaction of proteins with nascent quinones, catechol and 4-methylcatechol were oxidized with silver-I-oxide in glacial acetic acid or with mushroom tyrosinase (EC 1.10.3.1) in phosphate buffer, respectively. The structures identified indicate that not only the amine reacts with the quinone by the well known addition-oxidation-mechanism, but also that solvent molecules may participate in product formation. The main product of the oxidation of catechol in glacial acid is N-(2-carbomethoxyethyl)-phenoxaz-2,3-dione.", "contents": "[Reactions of nascent quinones with methyl beta-alanate in glacial acetic acid and in aqueous solution (author's transl)]. In order to generate a model for the reaction of proteins with nascent quinones, catechol and 4-methylcatechol were oxidized with silver-I-oxide in glacial acetic acid or with mushroom tyrosinase (EC 1.10.3.1) in phosphate buffer, respectively. The structures identified indicate that not only the amine reacts with the quinone by the well known addition-oxidation-mechanism, but also that solvent molecules may participate in product formation. The main product of the oxidation of catechol in glacial acid is N-(2-carbomethoxyethyl)-phenoxaz-2,3-dione."} {"id": "PMID:154229", "title": "[On the determination of changes in the large periodic structure of collagen (author's transl)].", "content": "Changes in the large periodic structure of collagen were investigated with the aid of synchrotron radiation. Following results were obtained: 1) Macroscopic extension results in elastic deformation of the elements which are determinant for the structure. 2) The increase of the large period is not proportional to the macroscopic stress. 3) The interpretation of these facts requires a mechanical coupling between the structural units. Up to extensions of 4% this coupling is produced by means of a viscoelastic matrix. 4) In all probability the polypeptide helices are deformed in an inhomogeneous mode. The results were set against measurements on human tendon and on artificially crosslinked collagen. The relations between the mechanical behaviour and the change of the large period were compared with the properties of a mathematical model.", "contents": "[On the determination of changes in the large periodic structure of collagen (author's transl)]. Changes in the large periodic structure of collagen were investigated with the aid of synchrotron radiation. Following results were obtained: 1) Macroscopic extension results in elastic deformation of the elements which are determinant for the structure. 2) The increase of the large period is not proportional to the macroscopic stress. 3) The interpretation of these facts requires a mechanical coupling between the structural units. Up to extensions of 4% this coupling is produced by means of a viscoelastic matrix. 4) In all probability the polypeptide helices are deformed in an inhomogeneous mode. The results were set against measurements on human tendon and on artificially crosslinked collagen. The relations between the mechanical behaviour and the change of the large period were compared with the properties of a mathematical model."} {"id": "PMID:154230", "title": "High-temperature inactivation of passive potassium transport in electrically non-excitable cells.", "content": "High-temperature inactivation of passive potassium transport is demonstrated for mouse cell cultures and discussed in analogy to recent results on model systems from phospholipid/cholesterol doted with channel-forming antibiotics.", "contents": "High-temperature inactivation of passive potassium transport in electrically non-excitable cells. High-temperature inactivation of passive potassium transport is demonstrated for mouse cell cultures and discussed in analogy to recent results on model systems from phospholipid/cholesterol doted with channel-forming antibiotics."} {"id": "PMID:154237", "title": "Spinal fusion for chronic low back pain.", "content": "Results of spinal fusion for chronic low back pain in 46 patients are analyzed, and the authors set forth the clinical circumstances in which the procedure may relieve this common complaint.", "contents": "Spinal fusion for chronic low back pain. Results of spinal fusion for chronic low back pain in 46 patients are analyzed, and the authors set forth the clinical circumstances in which the procedure may relieve this common complaint."} {"id": "PMID:154232", "title": "[Protein synthesis with cell extracts of Micrococcus radiodurans (author's transl)].", "content": "Pure active ribosomes of cells of Micrococcus radiodurans could be obtained when cultivated in trypton, glucose and nutrient broth by adding natrium citrate. The optimal conditions for a cell-free protein synthesis were investigated at the (polyuridylic acid) dependent polyphenylalanine synthesis. When exchanging ribosomes and S100-fractions with the corresponding fractions of E. coli, we found that the enzyme fractions of M. radiodurans extremely inhibit the ribosomal activity. The incorporation rates in the cell-free system of M. radiodurans yield, at comparable conditions, in relation to E. coli under 10%.", "contents": "[Protein synthesis with cell extracts of Micrococcus radiodurans (author's transl)]. Pure active ribosomes of cells of Micrococcus radiodurans could be obtained when cultivated in trypton, glucose and nutrient broth by adding natrium citrate. The optimal conditions for a cell-free protein synthesis were investigated at the (polyuridylic acid) dependent polyphenylalanine synthesis. When exchanging ribosomes and S100-fractions with the corresponding fractions of E. coli, we found that the enzyme fractions of M. radiodurans extremely inhibit the ribosomal activity. The incorporation rates in the cell-free system of M. radiodurans yield, at comparable conditions, in relation to E. coli under 10%."} {"id": "PMID:154233", "title": "[Circadian rhythm of metabolic rate in isolated tissue (author's transl)].", "content": "The circadian variation of oxygen uptake of isolated mouse diaphragm has been measured by means of the direct Warburg-technique in two series with sets of each 8 successive experiments. Under our experimental conditions oxygen uptake in the isolated diaphragm remains constant for 5 hours at least. The 24-hour period could therefore be completed with 8 single measurements of each 10--20 isolated diaphragms started at 3 h intervals with a overlap in experimental time of 2 h hours between each single experiment. Similar to the results concerning the spontaneous locomotive activity of the mouse (ASCHOFF 1955) we found maximum values of metabolic rate during the night, minimum values during day time and a interpolated relative maximum of oxygen uptake between 6(00)--8(00) h. Oxygen uptake after the stabilisation period of approximately 1 h seems to be determined by the time of the death of the animal.", "contents": "[Circadian rhythm of metabolic rate in isolated tissue (author's transl)]. The circadian variation of oxygen uptake of isolated mouse diaphragm has been measured by means of the direct Warburg-technique in two series with sets of each 8 successive experiments. Under our experimental conditions oxygen uptake in the isolated diaphragm remains constant for 5 hours at least. The 24-hour period could therefore be completed with 8 single measurements of each 10--20 isolated diaphragms started at 3 h intervals with a overlap in experimental time of 2 h hours between each single experiment. Similar to the results concerning the spontaneous locomotive activity of the mouse (ASCHOFF 1955) we found maximum values of metabolic rate during the night, minimum values during day time and a interpolated relative maximum of oxygen uptake between 6(00)--8(00) h. Oxygen uptake after the stabilisation period of approximately 1 h seems to be determined by the time of the death of the animal."} {"id": "PMID:154234", "title": "Studies supporting the concept of glyoxyperoxisomes as intermediary organelles in transformation of glyoxysomes into peroxisomes.", "content": "Intermediary forms of microbodies, glyoxyperoxisomes, are most likely synthesized at the stage of replacement of glyoxysomes by peroxisomes during the greening of fatstoring cells of cucumber cotyledons. This hypothesis is supported by three lines of results: 1. The levels of both glycollate oxidase and malate synthase are increased in the microbody fractions upon illumination of cotyledons. 2. Both peroxisomal and glyoxysomal marker enzymes are localized in organelles which exhibit the same buoyant densities. 3. De novo synthesis of malate synthase takes place even when irradiation already leads to a drastic increase of glycollate oxidase. The amount of malate synthase synthesized is almost identical in the light-induced system and in the dark control.", "contents": "Studies supporting the concept of glyoxyperoxisomes as intermediary organelles in transformation of glyoxysomes into peroxisomes. Intermediary forms of microbodies, glyoxyperoxisomes, are most likely synthesized at the stage of replacement of glyoxysomes by peroxisomes during the greening of fatstoring cells of cucumber cotyledons. This hypothesis is supported by three lines of results: 1. The levels of both glycollate oxidase and malate synthase are increased in the microbody fractions upon illumination of cotyledons. 2. Both peroxisomal and glyoxysomal marker enzymes are localized in organelles which exhibit the same buoyant densities. 3. De novo synthesis of malate synthase takes place even when irradiation already leads to a drastic increase of glycollate oxidase. The amount of malate synthase synthesized is almost identical in the light-induced system and in the dark control."} {"id": "PMID:154235", "title": "Growth and myelination of goldfish optic nerve fibers after retina regeneration and nerve crush.", "content": "Axonal regeneration in the optic nerve and tectum of the goldfish was studied both after retina regeneration and nerve crush. The retina regeneration was evoked by ouabain-induced damage of at least the ganglion cells and cells of the inner nuclear layer. The necrotic retinal neurons are substituted by mitotic processes in the outer nuclear layer and the marginal growth zone at the ora serrata. The axons of these newly developed retina ganglion cells grow through the degenerating, but mechanically undamaged, optic nerve into the tectum, establishing there synaptic contacts already 16 days after the intraocular ouabain-injection. The fibers were myelinated at first in the tectum, later on in the optic nerve. Thus, the myelination process proceeds in retrograde direction. About 60--80 days after injection the myelination has become nearly normalized. On the contra-lateral side of the same animal, the optic nerve was crushed near the eye-bulb. The axons of the original retina ganglion cells grow out into the degenerating optic nerve and tectum. They also find synaptic contacts and are myelinated in retrograde direction, but to a much lesser extent than the axons of the regenerated retina ganglion cells. An axonal factor is discussed, which would influence the oligodendroglial myelination activity. The effectiveness of this factor is probably dependent on the neuronal age and suggested to be triggered by the establishment of synaptic contacts.", "contents": "Growth and myelination of goldfish optic nerve fibers after retina regeneration and nerve crush. Axonal regeneration in the optic nerve and tectum of the goldfish was studied both after retina regeneration and nerve crush. The retina regeneration was evoked by ouabain-induced damage of at least the ganglion cells and cells of the inner nuclear layer. The necrotic retinal neurons are substituted by mitotic processes in the outer nuclear layer and the marginal growth zone at the ora serrata. The axons of these newly developed retina ganglion cells grow through the degenerating, but mechanically undamaged, optic nerve into the tectum, establishing there synaptic contacts already 16 days after the intraocular ouabain-injection. The fibers were myelinated at first in the tectum, later on in the optic nerve. Thus, the myelination process proceeds in retrograde direction. About 60--80 days after injection the myelination has become nearly normalized. On the contra-lateral side of the same animal, the optic nerve was crushed near the eye-bulb. The axons of the original retina ganglion cells grow out into the degenerating optic nerve and tectum. They also find synaptic contacts and are myelinated in retrograde direction, but to a much lesser extent than the axons of the regenerated retina ganglion cells. An axonal factor is discussed, which would influence the oligodendroglial myelination activity. The effectiveness of this factor is probably dependent on the neuronal age and suggested to be triggered by the establishment of synaptic contacts."} {"id": "PMID:154249", "title": "[Urological problems and genesis of the abdominal musculature aplasia syndrome].", "content": "Judging according to the frequent description of the syndrome of aplasia of the abdominal muscle above all in paediatric literature (up to now more than 250 cases), the knowledge of the symptomocomplex (aplasia of the abdominal muscle, malformations of the kidneys and the urinary tracts, cryptorchism) might be of particular interest for the urologist, since the urologic malformations decisively determine the prognosis quoad vitam of these patients. On the basis of three own cases the importance of the removal of infravesical obstruction is emphasized, whereas the reconstructive intervention for dilatation of upper urinary tracts is seldom mandatory.", "contents": "[Urological problems and genesis of the abdominal musculature aplasia syndrome]. Judging according to the frequent description of the syndrome of aplasia of the abdominal muscle above all in paediatric literature (up to now more than 250 cases), the knowledge of the symptomocomplex (aplasia of the abdominal muscle, malformations of the kidneys and the urinary tracts, cryptorchism) might be of particular interest for the urologist, since the urologic malformations decisively determine the prognosis quoad vitam of these patients. On the basis of three own cases the importance of the removal of infravesical obstruction is emphasized, whereas the reconstructive intervention for dilatation of upper urinary tracts is seldom mandatory."} {"id": "PMID:154250", "title": "[Uroflowmetry and its methodology. Normal limits. II. Normal range].", "content": "Prerequisite for every evaluation of a uroflowmetry curve are normal regions, on which the diagnostic evidence of the examination method is based. In the present paper a definite attitude to the limits of the normal was adopted, in which case apart from the course of the curve the relations from maximum flow to miction volume were entered. Diagrams of the normal region were established for men, women, and children, in which cases apart from the interindividual diffusion breadth also the individual diffusion breadth was taken into consideration. Error in the diagnostic course develop always then, when only mean values are taken into consideration. The critical consideration of the normal values to age seems to be important, in which cases a peak of the maximum values of the urinary flow is to be established between the 13th and the 40th year. In the later decades of life also without any subvesical obstruction an exponential function similar decrease of the maximum values of the flow develops.", "contents": "[Uroflowmetry and its methodology. Normal limits. II. Normal range]. Prerequisite for every evaluation of a uroflowmetry curve are normal regions, on which the diagnostic evidence of the examination method is based. In the present paper a definite attitude to the limits of the normal was adopted, in which case apart from the course of the curve the relations from maximum flow to miction volume were entered. Diagrams of the normal region were established for men, women, and children, in which cases apart from the interindividual diffusion breadth also the individual diffusion breadth was taken into consideration. Error in the diagnostic course develop always then, when only mean values are taken into consideration. The critical consideration of the normal values to age seems to be important, in which cases a peak of the maximum values of the urinary flow is to be established between the 13th and the 40th year. In the later decades of life also without any subvesical obstruction an exponential function similar decrease of the maximum values of the flow develops."} {"id": "PMID:154251", "title": "[DMF/S study of children with different duration of diabetes (author's transl)].", "content": "The objective of this study was to determine the DMF/S indices of 101 children, make regression analyses, and compare the regression coefficients of subjects, in whom diabetes mellitus became manifest before the beginning of secondary dentition, with the regession coefficients of patients with a duration of diabetes as long as three years. It has been found that in the case of manifestation of diabetes before the commencement of secondary dentition the D3-4 MF/S index was significantly lower compared to subjects with a duration of diabetes up to a maximum of three years and the DMF/S index of individual subjects was anything but low despite a specific diet.--From our present knowledge of the pathogenesis of caries it is possible to conclude that a high incidence of caries in the case of early manifestation of diabetes is due primarily to a lack of therapeutic cooperation of the patient.", "contents": "[DMF/S study of children with different duration of diabetes (author's transl)]. The objective of this study was to determine the DMF/S indices of 101 children, make regression analyses, and compare the regression coefficients of subjects, in whom diabetes mellitus became manifest before the beginning of secondary dentition, with the regession coefficients of patients with a duration of diabetes as long as three years. It has been found that in the case of manifestation of diabetes before the commencement of secondary dentition the D3-4 MF/S index was significantly lower compared to subjects with a duration of diabetes up to a maximum of three years and the DMF/S index of individual subjects was anything but low despite a specific diet.--From our present knowledge of the pathogenesis of caries it is possible to conclude that a high incidence of caries in the case of early manifestation of diabetes is due primarily to a lack of therapeutic cooperation of the patient."} {"id": "PMID:154252", "title": "[Oral examinations by exfoliative cytology of the healthy oral mucosa and inflammatorily altered gingiva (author's transl)].", "content": "Exfoliative cytology allows important information to be obtained about the structure and function of individual sections of tissue. Use of this particular method of examination is characterized by simplicity and freedom from strain on the subject being tested. In addition, the method yields clear and comprehensive results. Smears obtained from different regions of the oral cavities of subjects with clinically healthy oral mucous membrans and intact teeth were carefully analyzed. Also examined by clinical methods as well as by exfoliative cytology was the healthy gingiva, with parodontopathia inflammata superficialis and parodontopathia inflammata profunda serving as reference groups.", "contents": "[Oral examinations by exfoliative cytology of the healthy oral mucosa and inflammatorily altered gingiva (author's transl)]. Exfoliative cytology allows important information to be obtained about the structure and function of individual sections of tissue. Use of this particular method of examination is characterized by simplicity and freedom from strain on the subject being tested. In addition, the method yields clear and comprehensive results. Smears obtained from different regions of the oral cavities of subjects with clinically healthy oral mucous membrans and intact teeth were carefully analyzed. Also examined by clinical methods as well as by exfoliative cytology was the healthy gingiva, with parodontopathia inflammata superficialis and parodontopathia inflammata profunda serving as reference groups."} {"id": "PMID:154253", "title": "[Periodontal disease in the workers of paints and lacquer industry (author's transl)].", "content": "Examinations were performed by the author upon the influence of organic solvents and polycyclic aromatic hydrocarbons on parodontium in the workers of paints and lacquer industry. 195 persons employed in industry were examined. 100 persons whose conditions of work had no influence on their parodontium served as controls.--It was found that both, the frequency of incidents and the degree of intesity of changes in periodontium were significantly higher than those in the control group not exposed to the noxius action of work conditions.--This was analysed depending on sex, age, total time of employment and development of calculus dentis and plaques. The frequency, the intensivity of PI and the kind of parodontopathy was examined depending on various toxic condition at different working places. All statistical examinations were carried out by the use of the computer EMC ODRA 1305.", "contents": "[Periodontal disease in the workers of paints and lacquer industry (author's transl)]. Examinations were performed by the author upon the influence of organic solvents and polycyclic aromatic hydrocarbons on parodontium in the workers of paints and lacquer industry. 195 persons employed in industry were examined. 100 persons whose conditions of work had no influence on their parodontium served as controls.--It was found that both, the frequency of incidents and the degree of intesity of changes in periodontium were significantly higher than those in the control group not exposed to the noxius action of work conditions.--This was analysed depending on sex, age, total time of employment and development of calculus dentis and plaques. The frequency, the intensivity of PI and the kind of parodontopathy was examined depending on various toxic condition at different working places. All statistical examinations were carried out by the use of the computer EMC ODRA 1305."} {"id": "PMID:154254", "title": "[Cervico-facial actinomycosis--Frequency and change in a period of 29 years (author's transl)].", "content": "The clinical histories of 133 patients with cervicofacial actinomycosis, treated stationary in the period of 1948--1976, are interpreted in regard to patients age, treatment period and microbiological of histological proof. The opinions in literature about the frequency and a change of actinomycosis in the antibiotic era are discussed.", "contents": "[Cervico-facial actinomycosis--Frequency and change in a period of 29 years (author's transl)]. The clinical histories of 133 patients with cervicofacial actinomycosis, treated stationary in the period of 1948--1976, are interpreted in regard to patients age, treatment period and microbiological of histological proof. The opinions in literature about the frequency and a change of actinomycosis in the antibiotic era are discussed."} {"id": "PMID:154255", "title": "[Osteomyelitis of the temporomaxillary joint (author's transl)].", "content": "Although osteomyelitis of the inferior maxilla is still relatively frequently diagnosed, manifestation of the disease in the temporomaxillary joint is a rare occurrence. The symptomatology, diagnosis, and therapy of this particular arthropathy is discussed by reference to three cases treated in recent years at the Berlin Clinic of Maxillofacial Surgery. The importance of an early diagnosis and therapy is directed attention to because of the danger of serious subsequent diseases that may result in the loss of vital functions.", "contents": "[Osteomyelitis of the temporomaxillary joint (author's transl)]. Although osteomyelitis of the inferior maxilla is still relatively frequently diagnosed, manifestation of the disease in the temporomaxillary joint is a rare occurrence. The symptomatology, diagnosis, and therapy of this particular arthropathy is discussed by reference to three cases treated in recent years at the Berlin Clinic of Maxillofacial Surgery. The importance of an early diagnosis and therapy is directed attention to because of the danger of serious subsequent diseases that may result in the loss of vital functions."} {"id": "PMID:154257", "title": "[Clinical and experimental animal studies made to evaluate silastic and feeeze dried dura used in the treatment of orbital floor fractures (author's transl)].", "content": "A comparison has been made of the results obtained using Silastic and freeze-dried Dura in experiments on dogs treated for orbital floor fractures. Dura was found to be a better implant than Silastic because the former material will be completely resorbed and replaced by cicatricial connective tissue. Silastic tends to remain in its original site or position and may lead to secondary injuries because of its mobility. Accordingly, the latter material is indicated for use in the case of extensive fractures only.", "contents": "[Clinical and experimental animal studies made to evaluate silastic and feeeze dried dura used in the treatment of orbital floor fractures (author's transl)]. A comparison has been made of the results obtained using Silastic and freeze-dried Dura in experiments on dogs treated for orbital floor fractures. Dura was found to be a better implant than Silastic because the former material will be completely resorbed and replaced by cicatricial connective tissue. Silastic tends to remain in its original site or position and may lead to secondary injuries because of its mobility. Accordingly, the latter material is indicated for use in the case of extensive fractures only."} {"id": "PMID:154258", "title": "[On the isolation of streptococcus mutans from human dental plaques (author's transl)].", "content": "Using morphological and biochemical criteria, it was possible for Streptococcus mutans to be isolated, in one case, from the bacterial plaques obtained from three test subjects. The colonies of this clearly identified species were characterized by a granular surface resembling frosted glass, had attached to them a shining bubble, and were seen to split mannite and sorbite in the absence of conversion of glycerol.", "contents": "[On the isolation of streptococcus mutans from human dental plaques (author's transl)]. Using morphological and biochemical criteria, it was possible for Streptococcus mutans to be isolated, in one case, from the bacterial plaques obtained from three test subjects. The colonies of this clearly identified species were characterized by a granular surface resembling frosted glass, had attached to them a shining bubble, and were seen to split mannite and sorbite in the absence of conversion of glycerol."} {"id": "PMID:154259", "title": "[Superficial and marginal behavior of composite filling materials in class III and II cavities as compared with conventional filling materials (author's transl)].", "content": "The superficial and marginal behavior of composite filling materials is better than that of conventional types of front tooth filling cements as regards plaque retention, danger of marginal caries, and microleakage with potential damage to the pulp caused by bacterial toxins.--According to the results obtained in vitro, Evicrol is a positive alternative to Frontasil and Achatit-biochromatic. Plastic foils are not suitable as matrices, whereas aluminum matrices have been found to meet the requirements of surface smoothness and anatomical adaptability in cavity classes III, IV, and V. Celluloid matrices show inadequate adaptational properties, although they offer smoothest surfaces. The marginal behavior of Evicrol in class II cavities in molars is virtually the same in the case of both conventional retentive preparation and modified preparation of initial occlusal-approximal defects by the enamel etching technique. Discontinuous microretentive securing of matrix tags in the enamel etch pattern corresponds neither occlusally nor approximally to the physical definition of adhesion in different areas of the enamel. Clinical comparison in a 12-month study with the results obtained in vitro restricts safe indication to classes III and V, it being necessary to give careful consideration to the directions for use.--Long-term clinical longitudinal studies are required to determine permanent successes of treatment and possible extensions of the range of indications.", "contents": "[Superficial and marginal behavior of composite filling materials in class III and II cavities as compared with conventional filling materials (author's transl)]. The superficial and marginal behavior of composite filling materials is better than that of conventional types of front tooth filling cements as regards plaque retention, danger of marginal caries, and microleakage with potential damage to the pulp caused by bacterial toxins.--According to the results obtained in vitro, Evicrol is a positive alternative to Frontasil and Achatit-biochromatic. Plastic foils are not suitable as matrices, whereas aluminum matrices have been found to meet the requirements of surface smoothness and anatomical adaptability in cavity classes III, IV, and V. Celluloid matrices show inadequate adaptational properties, although they offer smoothest surfaces. The marginal behavior of Evicrol in class II cavities in molars is virtually the same in the case of both conventional retentive preparation and modified preparation of initial occlusal-approximal defects by the enamel etching technique. Discontinuous microretentive securing of matrix tags in the enamel etch pattern corresponds neither occlusally nor approximally to the physical definition of adhesion in different areas of the enamel. Clinical comparison in a 12-month study with the results obtained in vitro restricts safe indication to classes III and V, it being necessary to give careful consideration to the directions for use.--Long-term clinical longitudinal studies are required to determine permanent successes of treatment and possible extensions of the range of indications."} {"id": "PMID:154260", "title": "[Histological examinations of persisting milk teeth (author's transl)].", "content": "In twelve patients aged 13 to 24, histological examinations of twenty persistent milk teeth (with persistency having been due to aplasia of permanent teeth) showed that root resorptions are possible in such cases too. Cellular resorption results in the root being decomposed lacunally or linerly, respectively. The formation of osteodentin, which is a result of the phase of apposition and which is taking place in the pulp and along the surface of resorption, respectively, is considered a characteristic concomitant phenomenon. However, this tissue does not cause \"true ankylosis\". Accordingly, use of the term \"ankylosis\" to describe such cases is questionable. The author, on the strength of the results obtained in these studies, believes that root resorption of persistent milk teeth is a pathological process in the case of congenital absence of permanent teeth.", "contents": "[Histological examinations of persisting milk teeth (author's transl)]. In twelve patients aged 13 to 24, histological examinations of twenty persistent milk teeth (with persistency having been due to aplasia of permanent teeth) showed that root resorptions are possible in such cases too. Cellular resorption results in the root being decomposed lacunally or linerly, respectively. The formation of osteodentin, which is a result of the phase of apposition and which is taking place in the pulp and along the surface of resorption, respectively, is considered a characteristic concomitant phenomenon. However, this tissue does not cause \"true ankylosis\". Accordingly, use of the term \"ankylosis\" to describe such cases is questionable. The author, on the strength of the results obtained in these studies, believes that root resorption of persistent milk teeth is a pathological process in the case of congenital absence of permanent teeth."} {"id": "PMID:154261", "title": "[The registration of the retrusive closing phase and its effect on the mandible].", "content": "Retrusion of the mandible is of central importance to the diagnosis and therapy of functional discorders of the orofacial system. The change in width of the mandible is measured during recording this retruded position, and instructions for an appropriate mode of procedure are given.", "contents": "[The registration of the retrusive closing phase and its effect on the mandible]. Retrusion of the mandible is of central importance to the diagnosis and therapy of functional discorders of the orofacial system. The change in width of the mandible is measured during recording this retruded position, and instructions for an appropriate mode of procedure are given."} {"id": "PMID:154262", "title": "[Parodontal alterations caused by a deficiency of fibrin-stabilizing factor (factor XIII deficiency) (author's transl)].", "content": "This article reports the results of clinical, symptomatological, and histological examinations of the gingiva and parodontium in two patients with a hereditary deficiency of fibrinstabilizing factor (factor XIII deficiency).--In a period of observation of up to seventeen years the periodontal condition deteriorated until the teeth finally fell out.--Because of inadequate possibilities of mechanically reducing the plaque, changes of the gingiva in the form of granulomatous gingivitis accompanied by osteolysis were observed. The histological phenomena are characterized by strong nonspecific plasmacytic inflammation.", "contents": "[Parodontal alterations caused by a deficiency of fibrin-stabilizing factor (factor XIII deficiency) (author's transl)]. This article reports the results of clinical, symptomatological, and histological examinations of the gingiva and parodontium in two patients with a hereditary deficiency of fibrinstabilizing factor (factor XIII deficiency).--In a period of observation of up to seventeen years the periodontal condition deteriorated until the teeth finally fell out.--Because of inadequate possibilities of mechanically reducing the plaque, changes of the gingiva in the form of granulomatous gingivitis accompanied by osteolysis were observed. The histological phenomena are characterized by strong nonspecific plasmacytic inflammation."} {"id": "PMID:154263", "title": "[Evaluating the success of bringing the ends of fractured lower jaw bones into close apposition by means of plates and bolts (author's transl)].", "content": "The present paper analyzes the results of 100 osteosyntheses performed on 79 patients, with the ends of fractured lower jaw bones having been brought into close appostion through the use of plates and draw-in bolts. The major emphasis of this study centered on localizing the fracture and determining the etiology, the measures to be taken before performing an operation, the time of operation, and the duration of hospitalization.--Inflammatory disturbances of fracture healing were observed in 4 percent of the cases, and malocclusion was determined for another 4 percent of the cases included in this study. Also discussed by the author in his present paper are the results of post-hospital examinations of 51 patients, with 8 patients showing unesthetic operation scares. Temporary incapacity to work was, on average, 27.2 days for patients with isolated lower jaw bone fractures.--In conclusion, the author discusses the advantages and disadvantages of bringing the ends of fractured lower jaw bones into close apposition with the use of plates and bolts.", "contents": "[Evaluating the success of bringing the ends of fractured lower jaw bones into close apposition by means of plates and bolts (author's transl)]. The present paper analyzes the results of 100 osteosyntheses performed on 79 patients, with the ends of fractured lower jaw bones having been brought into close appostion through the use of plates and draw-in bolts. The major emphasis of this study centered on localizing the fracture and determining the etiology, the measures to be taken before performing an operation, the time of operation, and the duration of hospitalization.--Inflammatory disturbances of fracture healing were observed in 4 percent of the cases, and malocclusion was determined for another 4 percent of the cases included in this study. Also discussed by the author in his present paper are the results of post-hospital examinations of 51 patients, with 8 patients showing unesthetic operation scares. Temporary incapacity to work was, on average, 27.2 days for patients with isolated lower jaw bone fractures.--In conclusion, the author discusses the advantages and disadvantages of bringing the ends of fractured lower jaw bones into close apposition with the use of plates and bolts."} {"id": "PMID:154264", "title": "[The historical evolution of external cranio-maxillary fixation appliances for treatment of midfacial fractures (author's transl)].", "content": "The author describes the evolution stages of external cranio-maxillary fixation appliances from bandages, leather headbands, plaster headcaps and weight traction apparatus to head frame devices. Especially he describes recent halo frame and its importance for the treatment of midfacial fractures.", "contents": "[The historical evolution of external cranio-maxillary fixation appliances for treatment of midfacial fractures (author's transl)]. The author describes the evolution stages of external cranio-maxillary fixation appliances from bandages, leather headbands, plaster headcaps and weight traction apparatus to head frame devices. Especially he describes recent halo frame and its importance for the treatment of midfacial fractures."} {"id": "PMID:154265", "title": "[Changes in the activity of glucose-6-phosphate dehydrogenase and in the content of reduced glutathione in red blood corpuscles in the case of tumorous diseases in the maxillofacial region (author's transl)].", "content": "The activity of glucose-6-phosphate dehydrogenase and the glutathione content of red blood corpuscles were determined in twenty-five patients with tumors (of which nineteen were malignant and six, nonmalignant) as well as in a control group of twelve normal subjects. The activity of glucose-6-phosphate dehydrogenase was markedly higher in all of the tumor patients than it was in the controls. Also, the activity of glucose-6-phosphate dehydrogenase was found to increase with the time of existence of an untreated tumor.--Increased glutathione contents were determined especially in the early stages of tumor development. In patients with a relatively long record of malignant and nonmalignant tumorous diseases as well as in normal subjects there was observed no or only an inconsiderable increase in the content of glutathione.--This method of examination is assuming considerable importance for the differential diagnosis of tumors located in the maxillofacial region.", "contents": "[Changes in the activity of glucose-6-phosphate dehydrogenase and in the content of reduced glutathione in red blood corpuscles in the case of tumorous diseases in the maxillofacial region (author's transl)]. The activity of glucose-6-phosphate dehydrogenase and the glutathione content of red blood corpuscles were determined in twenty-five patients with tumors (of which nineteen were malignant and six, nonmalignant) as well as in a control group of twelve normal subjects. The activity of glucose-6-phosphate dehydrogenase was markedly higher in all of the tumor patients than it was in the controls. Also, the activity of glucose-6-phosphate dehydrogenase was found to increase with the time of existence of an untreated tumor.--Increased glutathione contents were determined especially in the early stages of tumor development. In patients with a relatively long record of malignant and nonmalignant tumorous diseases as well as in normal subjects there was observed no or only an inconsiderable increase in the content of glutathione.--This method of examination is assuming considerable importance for the differential diagnosis of tumors located in the maxillofacial region."} {"id": "PMID:154273", "title": "[Immunostaging (author's transl)].", "content": "This survey covers the problems of immunologic monitoring of patients and the spectrum of methods of diagnosing various types of immunopathological reactions.", "contents": "[Immunostaging (author's transl)]. This survey covers the problems of immunologic monitoring of patients and the spectrum of methods of diagnosing various types of immunopathological reactions."} {"id": "PMID:154276", "title": "[Use of intraspecific differentiation of Sh. sonnei for the purpose of studying patterns in the epidemic process of dysentery].", "content": "The use of complex typing of Sh. sonnei by the colicinogenic and enzymatic properties in epidemiological analysis of dysentery caused by Sh. sonnei, apart from establishment of epidemiological connections in the foci, offered a possibility of introducing significant corrections in the determination of the sizes and duration of existence of the epidemic foci, as well as in detection of the sources and factors of transmission of the infection established in epidemiological examination. Typing of Sh. sonnei also aided in ascertaining that, apart from general regularities in the individual territories, the epidemic process in individual groups of the population and in different seasons of the year could also course autonomously.", "contents": "[Use of intraspecific differentiation of Sh. sonnei for the purpose of studying patterns in the epidemic process of dysentery]. The use of complex typing of Sh. sonnei by the colicinogenic and enzymatic properties in epidemiological analysis of dysentery caused by Sh. sonnei, apart from establishment of epidemiological connections in the foci, offered a possibility of introducing significant corrections in the determination of the sizes and duration of existence of the epidemic foci, as well as in detection of the sources and factors of transmission of the infection established in epidemiological examination. Typing of Sh. sonnei also aided in ascertaining that, apart from general regularities in the individual territories, the epidemic process in individual groups of the population and in different seasons of the year could also course autonomously."} {"id": "PMID:154277", "title": "[Improving tetanus prevention in the Krasnodar area taking the current epidemic situation into account].", "content": "An increase of percentage of elderly persons among those who fell ill with tetanus (70%) was noted against a sharp reduction of tetanus incidence under the effect of mass active immunization against this disease. A study of immunity in older and elderly individuals showed the percentage of immune persons among them to be rather low (48.8--55.6%). Due to difficulty of elderly individuals embracement by vaccination the authors suggest a single immunization scheme with a double toxoid dose (20 BU) followed by revaccination with 10 BU in one year. A total of 21 472 persons were placed under observation. The suggested immunization scheme was harmless, promoted stimulation of antitetanus immunity in persons vaccinated earlier; as to unvaccinated persons--it created a favourable immunological preparedness for revaccination, permitting to do without any antitetanus serum in case of trauma.", "contents": "[Improving tetanus prevention in the Krasnodar area taking the current epidemic situation into account]. An increase of percentage of elderly persons among those who fell ill with tetanus (70%) was noted against a sharp reduction of tetanus incidence under the effect of mass active immunization against this disease. A study of immunity in older and elderly individuals showed the percentage of immune persons among them to be rather low (48.8--55.6%). Due to difficulty of elderly individuals embracement by vaccination the authors suggest a single immunization scheme with a double toxoid dose (20 BU) followed by revaccination with 10 BU in one year. A total of 21 472 persons were placed under observation. The suggested immunization scheme was harmless, promoted stimulation of antitetanus immunity in persons vaccinated earlier; as to unvaccinated persons--it created a favourable immunological preparedness for revaccination, permitting to do without any antitetanus serum in case of trauma."} {"id": "PMID:154278", "title": "[Incidence of meningococcal infection in the RSFSR].", "content": "The authors present characteristics of meningococcus infection epidemic process in case of sporadic cases and under epidemic conditions (1965--1976). A scheme of epidemiological analysis suggested by the authors permitted to differentiate and to record the incidence of various clinical forms of meningococcus infection, to present data on the age, seasonal characteristics, focality, etc. Comparison of intensive morbidity indices for 10 years, both at the individual administration territories and in the Republic as a whole demonstrated morbidity level of 1.5--2.0 to be one of prognostic signs of the beginning epidemic. The main features differentiating the sporadic and epidemic morbidity periods were revealed. The presence of group diseases, a greater percentage of children among those who fell ill, and marked signs of seasonality and territorial difference characterized the period of rise caused by meningococcus of serological group A.", "contents": "[Incidence of meningococcal infection in the RSFSR]. The authors present characteristics of meningococcus infection epidemic process in case of sporadic cases and under epidemic conditions (1965--1976). A scheme of epidemiological analysis suggested by the authors permitted to differentiate and to record the incidence of various clinical forms of meningococcus infection, to present data on the age, seasonal characteristics, focality, etc. Comparison of intensive morbidity indices for 10 years, both at the individual administration territories and in the Republic as a whole demonstrated morbidity level of 1.5--2.0 to be one of prognostic signs of the beginning epidemic. The main features differentiating the sporadic and epidemic morbidity periods were revealed. The presence of group diseases, a greater percentage of children among those who fell ill, and marked signs of seasonality and territorial difference characterized the period of rise caused by meningococcus of serological group A."} {"id": "PMID:154279", "title": "[Hydrodynamic and radiologic examination of the common bile duct].", "content": "The operative study of the common bile duct was carried out with the hydrodynamics methods (flow and resting pressure) in 433 patients and with the operative cholangiography in 383 patients. The hydrodynamics explorations pointed-out a margin of mistake due to falses positives and negatives of the 2.7% and the operative cholangiographies of the 8.6%. The association of both methods, hydrodynamics and radiologycs, allowed us to estimate that the diagnostic mistake is reduced to 0%. It is established in this work the necessity of carring out the flow, the measure of the resting pressure and the cholangiographies; in all the patients that are operated on the biliary tract because the diagnostic accuracy is the 100%. It is discussed the value of the diameter of the common bile duct for affirming the eventual existence of obstruction of the lower part of the common bile duct and the values are correlated, measured in mm., with pathological founds. It is considered the value of the hydrodynamics methods in the diagnostic of the stenosis of the sphincter of Oddi.", "contents": "[Hydrodynamic and radiologic examination of the common bile duct]. The operative study of the common bile duct was carried out with the hydrodynamics methods (flow and resting pressure) in 433 patients and with the operative cholangiography in 383 patients. The hydrodynamics explorations pointed-out a margin of mistake due to falses positives and negatives of the 2.7% and the operative cholangiographies of the 8.6%. The association of both methods, hydrodynamics and radiologycs, allowed us to estimate that the diagnostic mistake is reduced to 0%. It is established in this work the necessity of carring out the flow, the measure of the resting pressure and the cholangiographies; in all the patients that are operated on the biliary tract because the diagnostic accuracy is the 100%. It is discussed the value of the diameter of the common bile duct for affirming the eventual existence of obstruction of the lower part of the common bile duct and the values are correlated, measured in mm., with pathological founds. It is considered the value of the hydrodynamics methods in the diagnostic of the stenosis of the sphincter of Oddi."} {"id": "PMID:154280", "title": "The use of 75Se-methionine as a tracer of thrombocytopoiesis. I. In vivo incorporation of the tracer into platelet proteins: a biochemical study.", "content": "This study was undertaken to define to which platelet components 75Se-methionine is bound after its injection to normal rats, and to study the curves of specific radioactivity of each labelled fraction. It has been shown that, for a part, platelet labelling is due to adsorption of plasma proteins (albumin and fibrinogen) after their synthesis. For another part, methionine is directly incorporated in the bone marrow precursors into platelet actomyosin, a protein constituent of the cells; the variations of the specific radioactivity of this component indicate that 75Se-methionine can be used as a cohort label of platelets.", "contents": "The use of 75Se-methionine as a tracer of thrombocytopoiesis. I. In vivo incorporation of the tracer into platelet proteins: a biochemical study. This study was undertaken to define to which platelet components 75Se-methionine is bound after its injection to normal rats, and to study the curves of specific radioactivity of each labelled fraction. It has been shown that, for a part, platelet labelling is due to adsorption of plasma proteins (albumin and fibrinogen) after their synthesis. For another part, methionine is directly incorporated in the bone marrow precursors into platelet actomyosin, a protein constituent of the cells; the variations of the specific radioactivity of this component indicate that 75Se-methionine can be used as a cohort label of platelets."} {"id": "PMID:154281", "title": "Histochemical and ultrastructural study of human muscles after spontaneous rupture of the tendon.", "content": "The authors studied the histochemical and ultrastructural alterations of human muscles after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type 1 fibres), and ATPase (in type 2 fibres) activity decreased in all injured muscles. In the intact antagonists and in contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in the injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected antagonists muscles. 2 weeks or more after the rupture of the tendon, in the injured muscles the number of type 1 fibres were decreased and therefore a statistically significant type 2 fibre predominance occurred. Ultrastructurally the disruption and disorientation of the myofibrils, streaming and disorganisation of Z line were found. The sarcolemma was arranged, the sarcoplasmic reticulum was dilated; both normal, pycnotic and enlarged mitochondria were observed. The motor end-plates were not discernible.", "contents": "Histochemical and ultrastructural study of human muscles after spontaneous rupture of the tendon. The authors studied the histochemical and ultrastructural alterations of human muscles after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type 1 fibres), and ATPase (in type 2 fibres) activity decreased in all injured muscles. In the intact antagonists and in contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in the injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected antagonists muscles. 2 weeks or more after the rupture of the tendon, in the injured muscles the number of type 1 fibres were decreased and therefore a statistically significant type 2 fibre predominance occurred. Ultrastructurally the disruption and disorientation of the myofibrils, streaming and disorganisation of Z line were found. The sarcolemma was arranged, the sarcoplasmic reticulum was dilated; both normal, pycnotic and enlarged mitochondria were observed. The motor end-plates were not discernible."} {"id": "PMID:154282", "title": "The proliferative activity of myocardial capillary wall cells in variously aged swimming-exercised rats.", "content": "Cellular proliferation was studied by incorporation of 3H-thymidine in the hearts of young, adult and old swimming-exercised rats. The proliferative activity was measured by scintillation counting. The swimming exercise induced a significant proliferation of capillary wall cells in the younger age groups, suggesting a neoformation of myocardial capillaries in these rats, whereas no cell proliferation was recorded in the old rats.", "contents": "The proliferative activity of myocardial capillary wall cells in variously aged swimming-exercised rats. Cellular proliferation was studied by incorporation of 3H-thymidine in the hearts of young, adult and old swimming-exercised rats. The proliferative activity was measured by scintillation counting. The swimming exercise induced a significant proliferation of capillary wall cells in the younger age groups, suggesting a neoformation of myocardial capillaries in these rats, whereas no cell proliferation was recorded in the old rats."} {"id": "PMID:154284", "title": "Dose considerations in total skin electron irradiation for mycosis fungoides.", "content": "Two hundred patients with generalized cutaneous mycosis fungoides were treated with total skin electron irradiation (TSEI) in the Lahey Clinic Radiotherapy Department-MIT High Voltage Research Laboratory between 1964 and 1973. None of the patients had any clinical evidence of extracutaneous disease at presentation. The 3-year absolute survival rate was 54% (107 patients). Analysis of these 107 long-term survivors evaluated the relation between incidence of generalized cutaneous recurrence and total treatment dose given during the initial course of TSEI. Results indicated that in patients with erythroderma, the need for a second course of TSEI was inversely related to the total dose given during the first course. However, the curve seemed to flatten at about 1,500 cGy (rad). In plaque disease, the percentage of patients who received repeated courses of TSEI seemed to be relatively constant independent of total dose given during the initial course (65%-80%). In patients with tumor lesions, the incidence of generalized cutaneous recurrence was directly proportional to total dose. The optimal dose of TSEI for patients with mycosis fungoides may vary depending on types of skin lesions. Total dose during the initial course of TSEI should be kept relatively conservative, particularly in patients with generalized plaques where relapse rate is high allowing reserve of normal tissue tolerance for further TSEI when indicated.", "contents": "Dose considerations in total skin electron irradiation for mycosis fungoides. Two hundred patients with generalized cutaneous mycosis fungoides were treated with total skin electron irradiation (TSEI) in the Lahey Clinic Radiotherapy Department-MIT High Voltage Research Laboratory between 1964 and 1973. None of the patients had any clinical evidence of extracutaneous disease at presentation. The 3-year absolute survival rate was 54% (107 patients). Analysis of these 107 long-term survivors evaluated the relation between incidence of generalized cutaneous recurrence and total treatment dose given during the initial course of TSEI. Results indicated that in patients with erythroderma, the need for a second course of TSEI was inversely related to the total dose given during the first course. However, the curve seemed to flatten at about 1,500 cGy (rad). In plaque disease, the percentage of patients who received repeated courses of TSEI seemed to be relatively constant independent of total dose given during the initial course (65%-80%). In patients with tumor lesions, the incidence of generalized cutaneous recurrence was directly proportional to total dose. The optimal dose of TSEI for patients with mycosis fungoides may vary depending on types of skin lesions. Total dose during the initial course of TSEI should be kept relatively conservative, particularly in patients with generalized plaques where relapse rate is high allowing reserve of normal tissue tolerance for further TSEI when indicated."} {"id": "PMID:154287", "title": "[The current position of the transfer factor investigation (author's transl)].", "content": "This critical review has attempted to describe the current knowledge about the preparation and characterisation of transfer factor, the biological assays, and the tendency to therapy of patients with immunodeficiencies, chronic infectious diseases, and neoplastic diseases on the basic of results of the two last years. Hypotheses for the mechanism of functional activities of transfer factor are discussed.", "contents": "[The current position of the transfer factor investigation (author's transl)]. This critical review has attempted to describe the current knowledge about the preparation and characterisation of transfer factor, the biological assays, and the tendency to therapy of patients with immunodeficiencies, chronic infectious diseases, and neoplastic diseases on the basic of results of the two last years. Hypotheses for the mechanism of functional activities of transfer factor are discussed."} {"id": "PMID:154288", "title": "[Drug-induced bronchospasm (author's transl)].", "content": "A detailed review of drug-induced bronchospasm is presented. Four types of reactions are described. Furthermore, pathogenesis, clinical picture, treatment and prophylaxis of the \"Aspirin-induced asthma\" are demonstrated.", "contents": "[Drug-induced bronchospasm (author's transl)]. A detailed review of drug-induced bronchospasm is presented. Four types of reactions are described. Furthermore, pathogenesis, clinical picture, treatment and prophylaxis of the \"Aspirin-induced asthma\" are demonstrated."} {"id": "PMID:154289", "title": "[Comparative investigations of quantitative determination of cell-mediated immunity by skin test, macrophage migration inhibition test, and lymphocyte transformation test in guinea pigs (author's transl)].", "content": "Following an intradermal immunization of guinea pigs with bovine gamma globulin (BGG) and/or human serum albumin (HSA) emulsified in complete Freund's adjuvant we studied the cell-mediated immune response and its manipulation by 6-mercaptopurine. Three accepted correlates of cell-mediated immunity (CMI) have been used for the estimation of the immune reaction: - Intracutaneous test (IT) - Macrophage migration inhibition test (MMIT) - Lymphocyte transformation test (LTT). Comparative studies of quantitative determinations of CMI showed a correlation of the results of the in vitro test systems (MMIT and LTT) with the state of delayed hypersensitivity of the experimental animals, estimated by the IT in vivo. The cell-mediated immune response against BGG was much higher than that against HSA. This could be shown by all three test systems. We detected an immunosuppressive influence of 6-mercaptopurine on the CMI of guinea pigs, due to the dose and the mode of application. Thereby the in vitro test systems detected quantitative differences and indicated already a partial success of the immunosuppressive therapy, whereas the IT allowed a qualitative estimation only.", "contents": "[Comparative investigations of quantitative determination of cell-mediated immunity by skin test, macrophage migration inhibition test, and lymphocyte transformation test in guinea pigs (author's transl)]. Following an intradermal immunization of guinea pigs with bovine gamma globulin (BGG) and/or human serum albumin (HSA) emulsified in complete Freund's adjuvant we studied the cell-mediated immune response and its manipulation by 6-mercaptopurine. Three accepted correlates of cell-mediated immunity (CMI) have been used for the estimation of the immune reaction: - Intracutaneous test (IT) - Macrophage migration inhibition test (MMIT) - Lymphocyte transformation test (LTT). Comparative studies of quantitative determinations of CMI showed a correlation of the results of the in vitro test systems (MMIT and LTT) with the state of delayed hypersensitivity of the experimental animals, estimated by the IT in vivo. The cell-mediated immune response against BGG was much higher than that against HSA. This could be shown by all three test systems. We detected an immunosuppressive influence of 6-mercaptopurine on the CMI of guinea pigs, due to the dose and the mode of application. Thereby the in vitro test systems detected quantitative differences and indicated already a partial success of the immunosuppressive therapy, whereas the IT allowed a qualitative estimation only."} {"id": "PMID:154290", "title": "Immunological function of tonsils in atopic and nonatopic children, with special reference to E- and EAC-binding lymphocytes.", "content": "This investigation was carried out to determine the immunological function of the human tonsils, especially the role of lymphocytes of the atopic and nonatopic children. Authors introduced E- and EAC-rosettes forming technique with semi-quantitative evaluation of T and B lymphocytes in peripheral blood of 56 normal subjects, 28 atopic and 5 nonaptoic children of both sexes and different age. The percentage of T and B lymphocytes in removed palatine tonsils in 28 atopic and 5 nonatopic children was calculated. The percentage of rosettes forming cells in E and EAC suspensions appeared to be independent of age and sex. The percentage of T lymphocytes in peripheral blood is significantly higher than in the palatine tonsils whereas the percentage of B lymphocytes is significantly higher in the tonsils of atopic and nonatopic children than in the peripheral blood. The mean percentage of B lymphocytes in the tonsils of atopic children is significantly higher than in nonatopic children. The percentage of B lymphocytes was found to be significantly higher in hypertrophic than in small tonsils. Also, in the tonsils with adhesions there was a statistically significant higher percentage of EAC rosettes than in the tonsils free of adhesions. The percentage of T lymphocytes is statistically significant higher in the small tonsils.", "contents": "Immunological function of tonsils in atopic and nonatopic children, with special reference to E- and EAC-binding lymphocytes. This investigation was carried out to determine the immunological function of the human tonsils, especially the role of lymphocytes of the atopic and nonatopic children. Authors introduced E- and EAC-rosettes forming technique with semi-quantitative evaluation of T and B lymphocytes in peripheral blood of 56 normal subjects, 28 atopic and 5 nonaptoic children of both sexes and different age. The percentage of T and B lymphocytes in removed palatine tonsils in 28 atopic and 5 nonatopic children was calculated. The percentage of rosettes forming cells in E and EAC suspensions appeared to be independent of age and sex. The percentage of T lymphocytes in peripheral blood is significantly higher than in the palatine tonsils whereas the percentage of B lymphocytes is significantly higher in the tonsils of atopic and nonatopic children than in the peripheral blood. The mean percentage of B lymphocytes in the tonsils of atopic children is significantly higher than in nonatopic children. The percentage of B lymphocytes was found to be significantly higher in hypertrophic than in small tonsils. Also, in the tonsils with adhesions there was a statistically significant higher percentage of EAC rosettes than in the tonsils free of adhesions. The percentage of T lymphocytes is statistically significant higher in the small tonsils."} {"id": "PMID:154291", "title": "[Microlymphocytotoxic test with T lymphocytes: positivity by 3 hrs incubation (author's transl)].", "content": "Some human anti-HLA-DR and anti-HLA-A,B-sera contain cytotoxins reacting with T lymphocytes in the cytotoxic test by the prolongation of the incubation time to 3 hrs, whereas in the normal cytotoxic test of 1 1/2 hr incubation antibodies are not proved. These results suggest that simultaneous testing of sera with B and T lymphocytes not always give a true image of the actual occurrence of antibodies in the serum. The cause of the phenomen and the problem of the serological character of cytotoxins are discussed.", "contents": "[Microlymphocytotoxic test with T lymphocytes: positivity by 3 hrs incubation (author's transl)]. Some human anti-HLA-DR and anti-HLA-A,B-sera contain cytotoxins reacting with T lymphocytes in the cytotoxic test by the prolongation of the incubation time to 3 hrs, whereas in the normal cytotoxic test of 1 1/2 hr incubation antibodies are not proved. These results suggest that simultaneous testing of sera with B and T lymphocytes not always give a true image of the actual occurrence of antibodies in the serum. The cause of the phenomen and the problem of the serological character of cytotoxins are discussed."} {"id": "PMID:154293", "title": "Acromegaly and the heart. An echocardiographic study.", "content": "Twenty-seven patients with acromegaly had echocardiograms performed to delineate the ventricular septum, left ventricular posterior wall and mitral valve. Left ventricular function was assessed by calculating the systolic internal dimensional shortening of the left ventricle. Six patients met the criteria for asymmetric septal hypertrophy and eight had concentric left ventricular hypertrophy. The remaining 13 patients were categorized as \"normal,\" although six had septal measurements greater than 11 mm. The group with asymmetric septal hypertrophy had significantly greater percentage of internal dimensional shortening during systole than either the normal group (p less than 0.05) or the group with left ventricular hypertrophy (p less than 0.01). Initial mean growth hormone levels were considerably higher in the group with left ventricular hypertrophy than in the normal group (93 versus 34 ng/ml). Thus, echocardiographic abnormalities are common in acromegaly, and patients with asymmetric septal hypertrophy and acromegaly appear to have significantly increased ventricular ejection. Many of the patients with left ventricular hypertrophy have no evidence of clinical cardiovascular disease, and their left ventricular hypertrophy may be related to higher initial growth hormone levels.", "contents": "Acromegaly and the heart. An echocardiographic study. Twenty-seven patients with acromegaly had echocardiograms performed to delineate the ventricular septum, left ventricular posterior wall and mitral valve. Left ventricular function was assessed by calculating the systolic internal dimensional shortening of the left ventricle. Six patients met the criteria for asymmetric septal hypertrophy and eight had concentric left ventricular hypertrophy. The remaining 13 patients were categorized as \"normal,\" although six had septal measurements greater than 11 mm. The group with asymmetric septal hypertrophy had significantly greater percentage of internal dimensional shortening during systole than either the normal group (p less than 0.05) or the group with left ventricular hypertrophy (p less than 0.01). Initial mean growth hormone levels were considerably higher in the group with left ventricular hypertrophy than in the normal group (93 versus 34 ng/ml). Thus, echocardiographic abnormalities are common in acromegaly, and patients with asymmetric septal hypertrophy and acromegaly appear to have significantly increased ventricular ejection. Many of the patients with left ventricular hypertrophy have no evidence of clinical cardiovascular disease, and their left ventricular hypertrophy may be related to higher initial growth hormone levels."} {"id": "PMID:154295", "title": "Maternal age patterns and the incidence of Down's syndrome.", "content": "The incidence of Down's syndrome in three counties in southwestern Ontario from 1960 to 1974 was monitored in this retrospective descriptive study. Of 229, 754 live births including 292 Down's syndrome births, there was an incidence of 1.27/1,000 live births. The age-adjusted incidence for 288 cases where mother's age was known was 1.25/1,000. Data from Statistics Canada demonstrated a decrease in proportions of births to women over 35 years and a decrease in mean maternal age. The anticipated decrease in incidence of Down's syndrome because of these factors was not found; a real biological increase to women under 35 years cannot be ruled out.", "contents": "Maternal age patterns and the incidence of Down's syndrome. The incidence of Down's syndrome in three counties in southwestern Ontario from 1960 to 1974 was monitored in this retrospective descriptive study. Of 229, 754 live births including 292 Down's syndrome births, there was an incidence of 1.27/1,000 live births. The age-adjusted incidence for 288 cases where mother's age was known was 1.25/1,000. Data from Statistics Canada demonstrated a decrease in proportions of births to women over 35 years and a decrease in mean maternal age. The anticipated decrease in incidence of Down's syndrome because of these factors was not found; a real biological increase to women under 35 years cannot be ruled out."} {"id": "PMID:154296", "title": "Evaluation of a regional resource center for multiply handicapped retarded children.", "content": "A modified before--after, control-group evaluation design was employed to assess the impact of a demonstration program for multiply handicapped retarded children. Child development, parent and therapist attitudes, and knowledge and use of services were evaluated. Findings revealed no significant positive impact of the program on development, attitudes, and knowledge; the treatment group used more services. A significant change to a more negative attitude on the part of the treatment-group parents with regard to some aspects of normalization was found. Major impact of the program was in the area of coordination of services.", "contents": "Evaluation of a regional resource center for multiply handicapped retarded children. A modified before--after, control-group evaluation design was employed to assess the impact of a demonstration program for multiply handicapped retarded children. Child development, parent and therapist attitudes, and knowledge and use of services were evaluated. Findings revealed no significant positive impact of the program on development, attitudes, and knowledge; the treatment group used more services. A significant change to a more negative attitude on the part of the treatment-group parents with regard to some aspects of normalization was found. Major impact of the program was in the area of coordination of services."} {"id": "PMID:154297", "title": "Cortical evoked responses and response decrement in nonretarded and Down's syndrome individuals.", "content": "Cortical evoked responses were recorded from 66 nonretarded and 66 Down's syndrome subjects. Analyses of single-trial responses from which evoked responses were averaged indicated that visual evoked response amplitude in nonretarded subjects was more dependent on variability than on amplitude of single responses. Response decrement, the tendency for evoked responses to attenuate with repetitive stimulation, was clearly observed in the evoked responses of the nonretarded subjects but was minimal in those of the Down's syndrome group. The findings support the concept that the development of inhibitory processes in Down's syndrome persons' brains may be halted or delayed at an early age.", "contents": "Cortical evoked responses and response decrement in nonretarded and Down's syndrome individuals. Cortical evoked responses were recorded from 66 nonretarded and 66 Down's syndrome subjects. Analyses of single-trial responses from which evoked responses were averaged indicated that visual evoked response amplitude in nonretarded subjects was more dependent on variability than on amplitude of single responses. Response decrement, the tendency for evoked responses to attenuate with repetitive stimulation, was clearly observed in the evoked responses of the nonretarded subjects but was minimal in those of the Down's syndrome group. The findings support the concept that the development of inhibitory processes in Down's syndrome persons' brains may be halted or delayed at an early age."} {"id": "PMID:154298", "title": "Imitative behavior by Down's syndrome persons.", "content": "Three scales of imitative behavior (nonverbal, vocal, and verbal) were administered to 28 Down's syndrome subjects and 56 subjects with other diagnoses. All of the subjects were severely retarded and had at least partial vision and hearing, and the two groups were closely comparable with respect to sex, CA, and IQ. The results provided no support for the hypothesis--backed by a century of clinical observation--that individuals with Down's syndrome \"are outstanding in their mimicry\" (Belmont, 1971, p. 38).", "contents": "Imitative behavior by Down's syndrome persons. Three scales of imitative behavior (nonverbal, vocal, and verbal) were administered to 28 Down's syndrome subjects and 56 subjects with other diagnoses. All of the subjects were severely retarded and had at least partial vision and hearing, and the two groups were closely comparable with respect to sex, CA, and IQ. The results provided no support for the hypothesis--backed by a century of clinical observation--that individuals with Down's syndrome \"are outstanding in their mimicry\" (Belmont, 1971, p. 38)."} {"id": "PMID:154300", "title": "Characteristics of active Na transport in intact cardiac cells.", "content": "An active Na transport maintains the Na and K concentration gradients across the cell membrane of many cells and restores them following excitation. Heart muscle cells display frequent electrical discharges and thus the cardiac Na pump is of fundamental functional significance. Some methods for studying active Na transport are described. The active Na efflux from heart muscle cells is activated by an increase in the intracellular Na and the extracellular K concentration. The linkage between active Na efflux and active K influx varies widely according to the experimental conditions. The cardiac Na pump is electrogenic and can contribute directly to the membrane potential of the cells. The effects of active Na transport on contraction and intercellular coupling in myocardium are discussed.", "contents": "Characteristics of active Na transport in intact cardiac cells. An active Na transport maintains the Na and K concentration gradients across the cell membrane of many cells and restores them following excitation. Heart muscle cells display frequent electrical discharges and thus the cardiac Na pump is of fundamental functional significance. Some methods for studying active Na transport are described. The active Na efflux from heart muscle cells is activated by an increase in the intracellular Na and the extracellular K concentration. The linkage between active Na efflux and active K influx varies widely according to the experimental conditions. The cardiac Na pump is electrogenic and can contribute directly to the membrane potential of the cells. The effects of active Na transport on contraction and intercellular coupling in myocardium are discussed."} {"id": "PMID:154301", "title": "The trial use of clozapine for abnormal involuntary movement disorders.", "content": "Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind, placebo-controlled trial. The cohort consisted of individuals with Gilles de la Tourette's syndrome, Huntington's disease, and atypical persistent dyskinesia that was drug induced. Two subjects were dropped from the protocol due to complications. Two patients with Huntington's disease showed a marked decrease in movements; other individuals obtained no significant therapeutic benefits. Seven of the 10 patients completing the trial experienced moderate or marked side effects.", "contents": "The trial use of clozapine for abnormal involuntary movement disorders. Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind, placebo-controlled trial. The cohort consisted of individuals with Gilles de la Tourette's syndrome, Huntington's disease, and atypical persistent dyskinesia that was drug induced. Two subjects were dropped from the protocol due to complications. Two patients with Huntington's disease showed a marked decrease in movements; other individuals obtained no significant therapeutic benefits. Seven of the 10 patients completing the trial experienced moderate or marked side effects."} {"id": "PMID:154302", "title": "Electron microscopic study of the snout muscle spindles of the mole following denervation.", "content": "The authors examined electron microscopically the daily effects of the muscle spindles of the mole snout muscles following unilateral facial neurotomy. The denervated muscle spindles show first a degenerative sign of the sensory end bulb 1 day after the operation and later a degenerative sign of the intrafusal muscle fibers one week after the operation. The muscle spindles on the untreated side show first a degenerative sign of the intrafusal muscle fibers 2 weeks after the operation and later a degenerative sign of the sensory end bulb 20 days after the operation. 40 to 90 days after the operation, the spindles on both sides show the same degenerative signs, the intrafusal muscle fibers having become much thinner than the control.", "contents": "Electron microscopic study of the snout muscle spindles of the mole following denervation. The authors examined electron microscopically the daily effects of the muscle spindles of the mole snout muscles following unilateral facial neurotomy. The denervated muscle spindles show first a degenerative sign of the sensory end bulb 1 day after the operation and later a degenerative sign of the intrafusal muscle fibers one week after the operation. The muscle spindles on the untreated side show first a degenerative sign of the intrafusal muscle fibers 2 weeks after the operation and later a degenerative sign of the sensory end bulb 20 days after the operation. 40 to 90 days after the operation, the spindles on both sides show the same degenerative signs, the intrafusal muscle fibers having become much thinner than the control."} {"id": "PMID:154308", "title": "Effect of LH, prolactin and spermine on ATPase activity of human spermatozoa.", "content": "The effect of Prolactin and LH on the activity of spermatozoal ATPase was studied. Both the hormones activated the enzyme activity suggesting that these hormones, as they are present in the seminal fluid may influence the energy metabolism of spermatozoa. The spermine, a polyamine present in large concentration in the semen, had significantly enhanced the ATPase activity of the spermatozoa in a dose related manner.", "contents": "Effect of LH, prolactin and spermine on ATPase activity of human spermatozoa. The effect of Prolactin and LH on the activity of spermatozoal ATPase was studied. Both the hormones activated the enzyme activity suggesting that these hormones, as they are present in the seminal fluid may influence the energy metabolism of spermatozoa. The spermine, a polyamine present in large concentration in the semen, had significantly enhanced the ATPase activity of the spermatozoa in a dose related manner."} {"id": "PMID:154310", "title": "Actin filaments in human skin fibroblasts are similar in normal persons and patients with Huntington's disease.", "content": "Actin filaments in skin fibroblasts from patients with Huntington's disease (HD) were examined using immunofluorescent methods. Actin filaments were seen along the axis of cell elongation (stress or sheath filaments) as well as in areas of membrane ruffling (lattice filaments). In some cases, filaments appeared to radiate from foci within the cell. Bundles of these filaments radiated in various directions at different depths within a cell. These structures are similar, in cells from both normal individuals and HD patients, to actin filaments observed in other cell types. The higher-than-normal confluent densities achieved in culture by fibroblasts from patients with Huntington's chorea do not involve alterations in the ultrastructure of actin filaments.", "contents": "Actin filaments in human skin fibroblasts are similar in normal persons and patients with Huntington's disease. Actin filaments in skin fibroblasts from patients with Huntington's disease (HD) were examined using immunofluorescent methods. Actin filaments were seen along the axis of cell elongation (stress or sheath filaments) as well as in areas of membrane ruffling (lattice filaments). In some cases, filaments appeared to radiate from foci within the cell. Bundles of these filaments radiated in various directions at different depths within a cell. These structures are similar, in cells from both normal individuals and HD patients, to actin filaments observed in other cell types. The higher-than-normal confluent densities achieved in culture by fibroblasts from patients with Huntington's chorea do not involve alterations in the ultrastructure of actin filaments."} {"id": "PMID:154317", "title": "The prevalence of HBeAg and anti-HBe in an institution for the mentally retarded.", "content": "The age specific prevalence of HBsAg and anti-HBs was studied in 855 mentally retarded children and adults living in a large institution. The sera of every HBsAg positive patient was re-tested for the presence of HBeAg and anti-HBe. Overall, 78.2% of subjects showed serological evidence of current or past infection with HBV. The carrier rate was highest in children and young adults and higher amongst subjects with Down's syndrome than with other forms of retardation. HBeAg was detected in 33.9% of carriers and its prevalence also decreased with increasing age and was highest amongst subjects with Down's syndrome.", "contents": "The prevalence of HBeAg and anti-HBe in an institution for the mentally retarded. The age specific prevalence of HBsAg and anti-HBs was studied in 855 mentally retarded children and adults living in a large institution. The sera of every HBsAg positive patient was re-tested for the presence of HBeAg and anti-HBe. Overall, 78.2% of subjects showed serological evidence of current or past infection with HBV. The carrier rate was highest in children and young adults and higher amongst subjects with Down's syndrome than with other forms of retardation. HBeAg was detected in 33.9% of carriers and its prevalence also decreased with increasing age and was highest amongst subjects with Down's syndrome."} {"id": "PMID:154318", "title": "Laparoscopic tubal occlusion with silicone rubber bands.", "content": "Application of the silastic ring to the Fallopian tubes through the laparoscope seems to be a simple, safe and acceptable method of tubal sterilization. The technique and results in 337 patients are described. In the majority of cases, the procedure was effected in the outpatient department under local anaesthesia. Transsection of the tube (with or without bleeding), tearing of the mesosalpinx, and avulsion of the tube at the uterotubal junction were the most common complications; with experience and adherence to the proper technique of ring application, the above can be minimized. The pregnancy rate following this procedure seems to be acceptable, but long-term follow-up is necessary for definitive conclusions.", "contents": "Laparoscopic tubal occlusion with silicone rubber bands. Application of the silastic ring to the Fallopian tubes through the laparoscope seems to be a simple, safe and acceptable method of tubal sterilization. The technique and results in 337 patients are described. In the majority of cases, the procedure was effected in the outpatient department under local anaesthesia. Transsection of the tube (with or without bleeding), tearing of the mesosalpinx, and avulsion of the tube at the uterotubal junction were the most common complications; with experience and adherence to the proper technique of ring application, the above can be minimized. The pregnancy rate following this procedure seems to be acceptable, but long-term follow-up is necessary for definitive conclusions."} {"id": "PMID:154321", "title": "Prospects and services for medical rehabilitation.", "content": "In the developed world, comprehensive services for disabled patients are usually well established for children and elderly people. Services for rehabilitation of middle-aged patients generally consist of specific treatment facilities, such as for physiotherapy. On the other hand, a range of services of psychiatric patients is now established, with a model suitable for most disorders. Arrangements are flexible, ranging from crisis intervention to long-term care, in some places being remarkably comprehensive and well coordinated. There is a need to plan development of medical and social services for patients prone to chronic morbidity from whatever cause; this plan for the physicially disabled should take account of their many needs, and of the many facilities now available, some statutory, some voluntary. There is reason to believe that redeployment of resources existing in many countries could improve the standard of medical rehabilitation for patients of all ages.", "contents": "Prospects and services for medical rehabilitation. In the developed world, comprehensive services for disabled patients are usually well established for children and elderly people. Services for rehabilitation of middle-aged patients generally consist of specific treatment facilities, such as for physiotherapy. On the other hand, a range of services of psychiatric patients is now established, with a model suitable for most disorders. Arrangements are flexible, ranging from crisis intervention to long-term care, in some places being remarkably comprehensive and well coordinated. There is a need to plan development of medical and social services for patients prone to chronic morbidity from whatever cause; this plan for the physicially disabled should take account of their many needs, and of the many facilities now available, some statutory, some voluntary. There is reason to believe that redeployment of resources existing in many countries could improve the standard of medical rehabilitation for patients of all ages."} {"id": "PMID:154322", "title": "Purification and reaction mechanisms of the primary inhibitor of plasmin from human plasma.", "content": "The primary inhibitor of plasmin in human plasma was purified by a four-step procedure involving fractional (NH(4))(2)SO(4) precipitation, ion-exchange chromatography on a column of DEAE-Sepharose CL-6B and affinity chromatography on both a plasminogen-CH-Sepharose 4B column and a column of 6-aminohexanoic acid covalently coupled through the carboxylate function to AH-Sepharose 4B. No impurities in the final preparation could be detected when tested by immunoelectrophoresis against a range of specific antisera or against rabbit anti-human serum. On polyacrylamide-gel electrophoresis the inhibitor preparation showed a single band. The dissociation constant for the inhibitor-plasminogen complex was determined to be approx. 3mum at pH7.8. The reactions of the inhibitor with human plasmin and with bovine trypsin were studied. Comparison of the results obtained confirms the hypothesis previously presented, namely that the reaction of the inhibitor with plasmin involves at least two steps, the initial rapid formation of an enzyme-inhibitor complex followed by a slow irreversible transition to another complex. The results also indicate that the reaction of the inhibitor with trypsin involves just a single, irreversible step, so that this reaction seems to be less complicated than that of the inhibitor with plasmin. The ways in which 6-aminohexanoic acid influences the reactions were studied. The same value for the dissociation constant (approx. 26mum) for 6-aminohexanoic acid is obtained for both its effect on the reaction of the inhibitor with trypsin and for competitive inhibition of trypsin. The inhibitory effect of 6-aminohexanoic acid thus seems to be due to its blocking of the active site of trypsin. In contrast with this, the inhibitory effects of l-lysine and 6-aminohexanoic acid on the inhibitor-plasmin reaction occur at concentrations much too low to affect the active site of plasmin. The possible dependence of the reaction of the inhibitor with plasmin on a second site(s) on plasmin is discussed.", "contents": "Purification and reaction mechanisms of the primary inhibitor of plasmin from human plasma. The primary inhibitor of plasmin in human plasma was purified by a four-step procedure involving fractional (NH(4))(2)SO(4) precipitation, ion-exchange chromatography on a column of DEAE-Sepharose CL-6B and affinity chromatography on both a plasminogen-CH-Sepharose 4B column and a column of 6-aminohexanoic acid covalently coupled through the carboxylate function to AH-Sepharose 4B. No impurities in the final preparation could be detected when tested by immunoelectrophoresis against a range of specific antisera or against rabbit anti-human serum. On polyacrylamide-gel electrophoresis the inhibitor preparation showed a single band. The dissociation constant for the inhibitor-plasminogen complex was determined to be approx. 3mum at pH7.8. The reactions of the inhibitor with human plasmin and with bovine trypsin were studied. Comparison of the results obtained confirms the hypothesis previously presented, namely that the reaction of the inhibitor with plasmin involves at least two steps, the initial rapid formation of an enzyme-inhibitor complex followed by a slow irreversible transition to another complex. The results also indicate that the reaction of the inhibitor with trypsin involves just a single, irreversible step, so that this reaction seems to be less complicated than that of the inhibitor with plasmin. The ways in which 6-aminohexanoic acid influences the reactions were studied. The same value for the dissociation constant (approx. 26mum) for 6-aminohexanoic acid is obtained for both its effect on the reaction of the inhibitor with trypsin and for competitive inhibition of trypsin. The inhibitory effect of 6-aminohexanoic acid thus seems to be due to its blocking of the active site of trypsin. In contrast with this, the inhibitory effects of l-lysine and 6-aminohexanoic acid on the inhibitor-plasmin reaction occur at concentrations much too low to affect the active site of plasmin. The possible dependence of the reaction of the inhibitor with plasmin on a second site(s) on plasmin is discussed."} {"id": "PMID:154323", "title": "Kinetics and regulation of the myofibrillar adenosine triphosphatase.", "content": "1. The steady-state kinetic behaviour of the ATPase (adenosine triphosphatase) of intact myofibrils was studied in the presence of both high and low concentrations of Ca2+ (0.25 mM and less than 10 nM respectively). 2. Kinetic data were collected over the initial linear phase of the assay, which lasts for 20--60s. To obtain consistent data we found it necessary to use either fresh myofibril preparations or preparations that had been stored in the presence of thiol compounds. 3. When assayed in the presence of 0.25 mM-Ca2+, the myofibrillar ATPase obeyed Michaelis-Menten kinetics over the range 0.03--5.0 mM-MgATP (Km 16 +/- 6 micrometer, V 0.4 +/- 0.1 mumol/min per mg). 4. At low Ca2+ concentrations (less than 10 nM) the myofibrillar ATPase displayed pronounced substrate inhibition, which was not observed at high Ca2+ concentrations. Thus increasing the MgATP concentration had the net effect of decreasing the ATPase activity at low Ca2+ relative to that at high Ca2+. This preferential effect of MgATP on the low-Ca2+ ATPase may be important in Ca2+ control. 5. The substrate inhibition that was observed at low Ca2+ was lost on storage or thiol modification of the myofibrils. 6. Under physiological conditions (2 mM-MgATP, I 0.15, pH 7.0), the ATPase of fresh and thiol-protected myofibrils displayed approx. 100-fold activation by Ca2+.", "contents": "Kinetics and regulation of the myofibrillar adenosine triphosphatase. 1. The steady-state kinetic behaviour of the ATPase (adenosine triphosphatase) of intact myofibrils was studied in the presence of both high and low concentrations of Ca2+ (0.25 mM and less than 10 nM respectively). 2. Kinetic data were collected over the initial linear phase of the assay, which lasts for 20--60s. To obtain consistent data we found it necessary to use either fresh myofibril preparations or preparations that had been stored in the presence of thiol compounds. 3. When assayed in the presence of 0.25 mM-Ca2+, the myofibrillar ATPase obeyed Michaelis-Menten kinetics over the range 0.03--5.0 mM-MgATP (Km 16 +/- 6 micrometer, V 0.4 +/- 0.1 mumol/min per mg). 4. At low Ca2+ concentrations (less than 10 nM) the myofibrillar ATPase displayed pronounced substrate inhibition, which was not observed at high Ca2+ concentrations. Thus increasing the MgATP concentration had the net effect of decreasing the ATPase activity at low Ca2+ relative to that at high Ca2+. This preferential effect of MgATP on the low-Ca2+ ATPase may be important in Ca2+ control. 5. The substrate inhibition that was observed at low Ca2+ was lost on storage or thiol modification of the myofibrils. 6. Under physiological conditions (2 mM-MgATP, I 0.15, pH 7.0), the ATPase of fresh and thiol-protected myofibrils displayed approx. 100-fold activation by Ca2+."} {"id": "PMID:154330", "title": "Differential sensitivity of functional subsets of T cells to the cytotoxicity of natural T-lymphocytotoxic autoantibody of systemic lupus erythematosus.", "content": "A naturally occurring T-lymphocytotoxic autoantibody (Hu-NTA) in serum from a patient with systemic lupus erythematosus (SLE) showed a differential cytotoxic effect on functionally different T cell subsets as did natural thymocytotoxic autoantibody (NTA) of NZB mice. When the normal peripheral blood lymphocytes were treated, in the presence of complement, with Hu-NTA at a dilution that eliminated 25 to 30% of Hu-NTA-sensitive T cells, there was a marked reduction or a total depletion in the ability of resultant cells to show Con A-activated suppression on the proliferative response of responder cells in mixed lymphocyte reaction. The treatment of PBL in the same manner also resulted in a marked reduction in its responsiveness to Con A and PHA. However, the responder cells to allogeneic stimulator cells in MLR were found to be much more resistant to the cytotoxicity of Hu-NTA than other functional T cell subsets tested. These results suggest that Hu-NTA is responsible for the selective loss of certain functional T cell subsets including suppressor T cells in patients with SLE.", "contents": "Differential sensitivity of functional subsets of T cells to the cytotoxicity of natural T-lymphocytotoxic autoantibody of systemic lupus erythematosus. A naturally occurring T-lymphocytotoxic autoantibody (Hu-NTA) in serum from a patient with systemic lupus erythematosus (SLE) showed a differential cytotoxic effect on functionally different T cell subsets as did natural thymocytotoxic autoantibody (NTA) of NZB mice. When the normal peripheral blood lymphocytes were treated, in the presence of complement, with Hu-NTA at a dilution that eliminated 25 to 30% of Hu-NTA-sensitive T cells, there was a marked reduction or a total depletion in the ability of resultant cells to show Con A-activated suppression on the proliferative response of responder cells in mixed lymphocyte reaction. The treatment of PBL in the same manner also resulted in a marked reduction in its responsiveness to Con A and PHA. However, the responder cells to allogeneic stimulator cells in MLR were found to be much more resistant to the cytotoxicity of Hu-NTA than other functional T cell subsets tested. These results suggest that Hu-NTA is responsible for the selective loss of certain functional T cell subsets including suppressor T cells in patients with SLE."} {"id": "PMID:154331", "title": "Long term effectiveness of low dose mithramycin for Paget's disease of bone.", "content": "Nineteen patients with Paget's disease of bone were studied 7 months to 5 years after therapy with mithramycin in a dose averaging 11.5 microgram/kg body weight daily for 10 days. Thirteen patients, including 3 with the longest followup intervals, remained free of pain. Objective measures of disease activity (serum alkaline phosphatase level and 99mtechnetium pyrophosphate bone scan) were less favorable. There was no evidence of long term toxicity.", "contents": "Long term effectiveness of low dose mithramycin for Paget's disease of bone. Nineteen patients with Paget's disease of bone were studied 7 months to 5 years after therapy with mithramycin in a dose averaging 11.5 microgram/kg body weight daily for 10 days. Thirteen patients, including 3 with the longest followup intervals, remained free of pain. Objective measures of disease activity (serum alkaline phosphatase level and 99mtechnetium pyrophosphate bone scan) were less favorable. There was no evidence of long term toxicity."} {"id": "PMID:154332", "title": "[Cardiotocographic monitoring in pregnancy: some cases of sporadic decelerations (author's transl)].", "content": "The Authors are refering to the appearance of unknown deceleration in \"APC\" cardiotocograms. There is no relationship between these decelerations and the uterine contractions or fetal movements. These decelerations are called \"sporadic\" and are an indication of fetal risk. However, it is not necessary to have an immediate delivery.", "contents": "[Cardiotocographic monitoring in pregnancy: some cases of sporadic decelerations (author's transl)]. The Authors are refering to the appearance of unknown deceleration in \"APC\" cardiotocograms. There is no relationship between these decelerations and the uterine contractions or fetal movements. These decelerations are called \"sporadic\" and are an indication of fetal risk. However, it is not necessary to have an immediate delivery."} {"id": "PMID:154342", "title": "Congenital non-spherocytic haemolytic anaemia variants with primary and secondary pyruvate kinase deficiency. I. Erythrokinetic patterns.", "content": "The patterns of survival of isotope-labelled erythrocytes were examined in patients suffering from two variants of congenital non-spherocytic haemolytic anaemia with decreased erythrocyte pyruvate kinase (PK) activity. In one variant, with primary PK defect (PPKD) random destruction of erythrocytes was predominant in the process of haemolysis. In the second variant, with primary magnesium activated adenosine triphosphatase (ATP-ase) (Mg++) deficiency and a secondary decrease in PK activity, erythrocytes were destroyed by senescence. Two subpopulations of labelled erythrocytes with different destruction rates were observed in all patients examined, except one with the second variant, with very mild haemolysis. Splenectomy, performed on two patient, was successful only in the variant with PPKD.", "contents": "Congenital non-spherocytic haemolytic anaemia variants with primary and secondary pyruvate kinase deficiency. I. Erythrokinetic patterns. The patterns of survival of isotope-labelled erythrocytes were examined in patients suffering from two variants of congenital non-spherocytic haemolytic anaemia with decreased erythrocyte pyruvate kinase (PK) activity. In one variant, with primary PK defect (PPKD) random destruction of erythrocytes was predominant in the process of haemolysis. In the second variant, with primary magnesium activated adenosine triphosphatase (ATP-ase) (Mg++) deficiency and a secondary decrease in PK activity, erythrocytes were destroyed by senescence. Two subpopulations of labelled erythrocytes with different destruction rates were observed in all patients examined, except one with the second variant, with very mild haemolysis. Splenectomy, performed on two patient, was successful only in the variant with PPKD."} {"id": "PMID:154343", "title": "Congenital non-spherocytic haemolytic anaemia variants with primary and secondary pyruvate kinase deficiency. II. Enzymatic studies.", "content": "Some metabolic effects associated with defective pyruvate kinase (PK) in two variants of congenital non-spherocytic haemolytic anaemia with primary PK and primary adenosine triphosphatase (ATP-ase) (Mg++) deficiency respectively we compared. In one patient with a low erythrocyte ATP level, decreased PK activity appeared together with the irreversible loss of its sensitivity to fructose-I,6-diphosphate (FDP), independently of the experimental conditions. In the second patient, the decrease in PK activity associated with an elevated erythrocyte ATP level was a secondary effect, due to primary ATP-ase (Mg++) deficiency. Removal of excessive amounts of ATP, by dialysis of haemolysates or their in-vitro treatment with ATP-ase, increased PK activity to the normal range and restored its sensitivity to the stimulatory effect of FDP. Similar effects could be obtained after i.v. administration of magnesium laevulinate. Under these in vivo conditions the ATP level was normalized after a transient rise ATP-ase activity, the PK activity increased and its sensitivity to FDP reappeared.", "contents": "Congenital non-spherocytic haemolytic anaemia variants with primary and secondary pyruvate kinase deficiency. II. Enzymatic studies. Some metabolic effects associated with defective pyruvate kinase (PK) in two variants of congenital non-spherocytic haemolytic anaemia with primary PK and primary adenosine triphosphatase (ATP-ase) (Mg++) deficiency respectively we compared. In one patient with a low erythrocyte ATP level, decreased PK activity appeared together with the irreversible loss of its sensitivity to fructose-I,6-diphosphate (FDP), independently of the experimental conditions. In the second patient, the decrease in PK activity associated with an elevated erythrocyte ATP level was a secondary effect, due to primary ATP-ase (Mg++) deficiency. Removal of excessive amounts of ATP, by dialysis of haemolysates or their in-vitro treatment with ATP-ase, increased PK activity to the normal range and restored its sensitivity to the stimulatory effect of FDP. Similar effects could be obtained after i.v. administration of magnesium laevulinate. Under these in vivo conditions the ATP level was normalized after a transient rise ATP-ase activity, the PK activity increased and its sensitivity to FDP reappeared."} {"id": "PMID:154344", "title": "Inhibition of the (Ca2+)ATPase from sarcoplasmic reticulum by dicyclohexylcarbodiimide: evidence for location of the Ca2+ binding site in a hydrophobic region.", "content": "Dicyclohexylcarbodiimide (DCCD) inhibits the (Ca2+)ATPase, Ca2+ uptake by sarcoplasmic reticulum vesicles and Ca2+ binding to the (Ca2+)ATPase from sarcoplasmic reticulum. Ca2+ (at micron concentrations) specifically protects against DCCD inhibition. The inhibition can, therefore, be readily demonstrated only in the presence of Ca2+ chelating agents such as EGTA. In the presence of EGTA, the ionophore A-23187 increased the sensitivity to DCCD. The ionophore also increased the phosphorylation of the enzyme by inorganic phosphate in the presence of Mg2+. These results indicate that tightly bound Ca2+ is located in a hydrophobic region of the enzyme which is not accessible to EGTA. Complete inhibition of the (Ca2+)ATPase is accompanied by binding of 4--5 nmol of [14C]DCCD per mg of ATPase protein in the absence of Ca2+ compared with 2 nmol bound per mg in the presence of Ca2+ with no ATPase inhibition. Assuming a molecular weight of 100 000 for the ATPase monomer, about 1 nmol of DCCD inhibits 4 nmol of ATPase. This result suggests that the minimal functional unit of the enzyme is a tetramer. Following trypsin digestion of the [14C]DCCD-labeled ATPase most of the radioactivity appears in the 20 000-dalton fragment. We propose that DCCD reacts with the Ca2+-binding site of the ATPase.", "contents": "Inhibition of the (Ca2+)ATPase from sarcoplasmic reticulum by dicyclohexylcarbodiimide: evidence for location of the Ca2+ binding site in a hydrophobic region. Dicyclohexylcarbodiimide (DCCD) inhibits the (Ca2+)ATPase, Ca2+ uptake by sarcoplasmic reticulum vesicles and Ca2+ binding to the (Ca2+)ATPase from sarcoplasmic reticulum. Ca2+ (at micron concentrations) specifically protects against DCCD inhibition. The inhibition can, therefore, be readily demonstrated only in the presence of Ca2+ chelating agents such as EGTA. In the presence of EGTA, the ionophore A-23187 increased the sensitivity to DCCD. The ionophore also increased the phosphorylation of the enzyme by inorganic phosphate in the presence of Mg2+. These results indicate that tightly bound Ca2+ is located in a hydrophobic region of the enzyme which is not accessible to EGTA. Complete inhibition of the (Ca2+)ATPase is accompanied by binding of 4--5 nmol of [14C]DCCD per mg of ATPase protein in the absence of Ca2+ compared with 2 nmol bound per mg in the presence of Ca2+ with no ATPase inhibition. Assuming a molecular weight of 100 000 for the ATPase monomer, about 1 nmol of DCCD inhibits 4 nmol of ATPase. This result suggests that the minimal functional unit of the enzyme is a tetramer. Following trypsin digestion of the [14C]DCCD-labeled ATPase most of the radioactivity appears in the 20 000-dalton fragment. We propose that DCCD reacts with the Ca2+-binding site of the ATPase."} {"id": "PMID:154347", "title": "Transport characteristics of frog gastric membranes.", "content": "ATP-induced transport by fractions of frog gastric microsomes prepared either by density gradient centrifugation of by free flow electrophoresis were K+ dependent and hence considered due to a K+-activated ATPase. Significant activity of this enzyme was, however, only found in the anodic peak of the free flow electrophoretic separation, which in addition to separating transporting from non-transporting particles, also separated membranes containing a phosphorylatable peptide (Mr=105 000) region as the major peptide on SDS-polyacrylamide gel electrophoresis from those containing a peptide (Mr=44 000) on SDS-polyacrylamide gel electrophoresis. H+ uptake, measured either by acridine orange or 3,3'-diethyloxadicarbocyanine + tetrachlorosalicylanilide absorbance changes was dependent on K+ intravesicularly. Using 86Rb+, active extrusion of the cation followed ATP addition. SCN-, an inhibitor of acid secretion did not affect the latter, but blocked signals due to H+ uptake, in contrast to mammalian preparations.", "contents": "Transport characteristics of frog gastric membranes. ATP-induced transport by fractions of frog gastric microsomes prepared either by density gradient centrifugation of by free flow electrophoresis were K+ dependent and hence considered due to a K+-activated ATPase. Significant activity of this enzyme was, however, only found in the anodic peak of the free flow electrophoretic separation, which in addition to separating transporting from non-transporting particles, also separated membranes containing a phosphorylatable peptide (Mr=105 000) region as the major peptide on SDS-polyacrylamide gel electrophoresis from those containing a peptide (Mr=44 000) on SDS-polyacrylamide gel electrophoresis. H+ uptake, measured either by acridine orange or 3,3'-diethyloxadicarbocyanine + tetrachlorosalicylanilide absorbance changes was dependent on K+ intravesicularly. Using 86Rb+, active extrusion of the cation followed ATP addition. SCN-, an inhibitor of acid secretion did not affect the latter, but blocked signals due to H+ uptake, in contrast to mammalian preparations."} {"id": "PMID:154349", "title": "[Some peculiarities of ATPase in tumor mitochondria].", "content": "The oxidative phosphorylation and ATPase activity (initial and stimulated by DNP and Mg2+) in tumor mitochondria were investigated. The intact mitochondria of Zajdela hepatoma, in contrast to liver mitochondria, exhibit the ATPase activity which is slightly stimulated by 2,4-dinitrophenol and is markedly activated by Mg2+. The mitochondria from transplantable solid tumors (adenocarcinoma 755, Iensen sarcoma, sarcoma 45) despite satisfactory morphological integrity under electron microscopy are biochemically less intact than the mitochondria of hepatoma. ATPase of these mitochondria is also slightly stimulated by 2,4-dinitrophenol and significantly by Mg2+. The ATPase activity of thymus mitochondria, the normal tissue with sufficiently high proliferative activity, corresponds to that of tumor mitochondria. The total amount of enzyme in mitochondria of tumors investigated and thymus is not lowered, since the ATPase activity in the presence of both DNP and Mg2+ corresponds to the ATPase activity of liver mitochondria. The Mg2+ ATPase activity of tumor mitochondria is not sensitive or is only partly sensitive to oligomycin. The data obtained are indicative of a high lability of the phosphorylating system in tumor and thymus mitochondria. A possibility of reorganization of the energy mechanism of tumor mitochondria and some normal tissues in connection with increased metabolism requiring high energy consumption, is discussed.", "contents": "[Some peculiarities of ATPase in tumor mitochondria]. The oxidative phosphorylation and ATPase activity (initial and stimulated by DNP and Mg2+) in tumor mitochondria were investigated. The intact mitochondria of Zajdela hepatoma, in contrast to liver mitochondria, exhibit the ATPase activity which is slightly stimulated by 2,4-dinitrophenol and is markedly activated by Mg2+. The mitochondria from transplantable solid tumors (adenocarcinoma 755, Iensen sarcoma, sarcoma 45) despite satisfactory morphological integrity under electron microscopy are biochemically less intact than the mitochondria of hepatoma. ATPase of these mitochondria is also slightly stimulated by 2,4-dinitrophenol and significantly by Mg2+. The ATPase activity of thymus mitochondria, the normal tissue with sufficiently high proliferative activity, corresponds to that of tumor mitochondria. The total amount of enzyme in mitochondria of tumors investigated and thymus is not lowered, since the ATPase activity in the presence of both DNP and Mg2+ corresponds to the ATPase activity of liver mitochondria. The Mg2+ ATPase activity of tumor mitochondria is not sensitive or is only partly sensitive to oligomycin. The data obtained are indicative of a high lability of the phosphorylating system in tumor and thymus mitochondria. A possibility of reorganization of the energy mechanism of tumor mitochondria and some normal tissues in connection with increased metabolism requiring high energy consumption, is discussed."} {"id": "PMID:154350", "title": "[Phospholipid composition and enzyme activity of mitochondrial ATPase complexes].", "content": "The phospholipid composition of oligomycin-sensitive ATPase fractions from mitochondria, precipitated under different ammonium sulfate concentrations according to the Kagawa-Racker method, was studied. The ATPase activity of the isolated fractions was found to be correlated with the levels of their phospholipase and esterase activities.", "contents": "[Phospholipid composition and enzyme activity of mitochondrial ATPase complexes]. The phospholipid composition of oligomycin-sensitive ATPase fractions from mitochondria, precipitated under different ammonium sulfate concentrations according to the Kagawa-Racker method, was studied. The ATPase activity of the isolated fractions was found to be correlated with the levels of their phospholipase and esterase activities."} {"id": "PMID:154351", "title": "[Disruption of the Ca++ transport enzyme system in sarcoplasmic reticulum membranes upon exposure to phospholipid hydroperoxides and fatty acid hydroperoxides].", "content": "It was shown that when injected into a suspension of sarcoplasmic reticulum (SR) vesicles phosphatidyl ethanol-amine hydroperoxide (HP) slightly activated Ca++-dependent ATPase and increased the permeability of SR membranes for Ca++ during the enzyme function. Linoleic acid HP had no effect on the parameters of the enzymatic Ca++- transporting system (activity of Ca++-dependent ATPase, Ca/ATP ratio, rate of Ca++ efflux) in the SR membranes due to its insufficient incorporation into the SR fragments. It is concluded that among the primary molecular products of lipid peroxidation (free fatty acid HP, phospholipid HP) induced both in vitro (by the Fe++ + ascorbate system) and in vivo (ischemia, E-avitaminosis), only the phospholipid HPs were modifiers of Ca++ transport in the SR membranes.", "contents": "[Disruption of the Ca++ transport enzyme system in sarcoplasmic reticulum membranes upon exposure to phospholipid hydroperoxides and fatty acid hydroperoxides]. It was shown that when injected into a suspension of sarcoplasmic reticulum (SR) vesicles phosphatidyl ethanol-amine hydroperoxide (HP) slightly activated Ca++-dependent ATPase and increased the permeability of SR membranes for Ca++ during the enzyme function. Linoleic acid HP had no effect on the parameters of the enzymatic Ca++- transporting system (activity of Ca++-dependent ATPase, Ca/ATP ratio, rate of Ca++ efflux) in the SR membranes due to its insufficient incorporation into the SR fragments. It is concluded that among the primary molecular products of lipid peroxidation (free fatty acid HP, phospholipid HP) induced both in vitro (by the Fe++ + ascorbate system) and in vivo (ischemia, E-avitaminosis), only the phospholipid HPs were modifiers of Ca++ transport in the SR membranes."} {"id": "PMID:154352", "title": "Selectivity of action of 5-FU: biochemical basis.", "content": "Studies have been initiated to investigate the biochemical basis for selectivity of action of 5-fluorouracil against tumor cells. These studies included the measurement of 5-fluorodeoxyuridine monophosphate pools and the amount of 5-fluorouracil incorporated into RNA at various times following the administration of labeled 5-fluorouracil-6-3H, 5-fluorouridine-6-3H and 5-fluorodeoxyuridine-6-3H to animals bearing sensitive L1210 cells and L1210 resistant to 5-fluorouracil. The data indicate that: 1) in both cell lines the order of drug uptake into cells in vivo was in the order of fluorouride greater than fluorouracil greater then fluorodeoxyuridine; 2) there was no qualitative difference between the two cell lines in term of the extent of drug activation; 3) the data suggest a strong correlation between the amount of 5-fluorodeoxyuridine-monophosphates formed and retained at the target site and responsiveness to these agents. The effects of thymidine administered by continuous infusion and i.v. bolus injection on the antitumor activity of 5-fluorouracil was also investigated in animals bearing the induced colon carcinoma. The data suggest that thymidine, in combination with 5-fluorouracil, improves the therapeutic index of 5-fluorouracil. Initial studies on the metabolism of 5-fluorouracil in patients bearing the colon carcinoma are also reported herein.", "contents": "Selectivity of action of 5-FU: biochemical basis. Studies have been initiated to investigate the biochemical basis for selectivity of action of 5-fluorouracil against tumor cells. These studies included the measurement of 5-fluorodeoxyuridine monophosphate pools and the amount of 5-fluorouracil incorporated into RNA at various times following the administration of labeled 5-fluorouracil-6-3H, 5-fluorouridine-6-3H and 5-fluorodeoxyuridine-6-3H to animals bearing sensitive L1210 cells and L1210 resistant to 5-fluorouracil. The data indicate that: 1) in both cell lines the order of drug uptake into cells in vivo was in the order of fluorouride greater than fluorouracil greater then fluorodeoxyuridine; 2) there was no qualitative difference between the two cell lines in term of the extent of drug activation; 3) the data suggest a strong correlation between the amount of 5-fluorodeoxyuridine-monophosphates formed and retained at the target site and responsiveness to these agents. The effects of thymidine administered by continuous infusion and i.v. bolus injection on the antitumor activity of 5-fluorouracil was also investigated in animals bearing the induced colon carcinoma. The data suggest that thymidine, in combination with 5-fluorouracil, improves the therapeutic index of 5-fluorouracil. Initial studies on the metabolism of 5-fluorouracil in patients bearing the colon carcinoma are also reported herein."} {"id": "PMID:154348", "title": "Structure and mechanism of catalytic action of active sites of nitrogenase.", "content": "A review of the data on the macromolecular structure of nitrogenase and its individual fragments, the electronic structure of iron- and molybdenum-containing components of the active site, and the functional groups of the ATPase site of the enzyme is given. Reactions of N2 reduction, ATP hydrolysis, and H2 evolution, inhibitory processes, and electron transport reactions catalyzed by the enzyme are analyzed within the framework of a general kinetic model. The results of an investigation of the location of the iron-containing cluster system of electron transport, the ATPase site, and the N2-binding and reducing site on the nitrogenase macro-molecule with the aid of a new complex approach including methods of spin, luminescent, and electron-dense labeling are described. On the basis of a number of physicochemical and kinetic data a model of the structure and mechanism of action of the active site of nitrogenase is proposed, which assumes four-step electron transfer from an external reducing agent along the chain of ferredoxin-like iron-containing clusters of the enzyme and an increase in the reducing potential of the iron clusters through the energy of ATP hydrolysis and four-electron reduction in a binuclear molybdenum-containing complex.", "contents": "Structure and mechanism of catalytic action of active sites of nitrogenase. A review of the data on the macromolecular structure of nitrogenase and its individual fragments, the electronic structure of iron- and molybdenum-containing components of the active site, and the functional groups of the ATPase site of the enzyme is given. Reactions of N2 reduction, ATP hydrolysis, and H2 evolution, inhibitory processes, and electron transport reactions catalyzed by the enzyme are analyzed within the framework of a general kinetic model. The results of an investigation of the location of the iron-containing cluster system of electron transport, the ATPase site, and the N2-binding and reducing site on the nitrogenase macro-molecule with the aid of a new complex approach including methods of spin, luminescent, and electron-dense labeling are described. On the basis of a number of physicochemical and kinetic data a model of the structure and mechanism of action of the active site of nitrogenase is proposed, which assumes four-step electron transfer from an external reducing agent along the chain of ferredoxin-like iron-containing clusters of the enzyme and an increase in the reducing potential of the iron clusters through the energy of ATP hydrolysis and four-electron reduction in a binuclear molybdenum-containing complex."} {"id": "PMID:154353", "title": "Potential clinical applications of a new method for quantitation of plasma levels of 5-fluorouracil and 5-fluorodeoxyuridine.", "content": "A new high-pressure liquid chromatographic method for the clinical assay of 5-fluorouracil and 5-fluoroudexyuridine has been developed. The sensitivity and specificity of the method equals that of gas chromatography/mass spectrometric methods. The practical value of the method has been demonstrated by its application in several preliminary clinical studies of 5-fluorouracil in which plasma levels of 10(-8)-10(-6)M were readily monitored.", "contents": "Potential clinical applications of a new method for quantitation of plasma levels of 5-fluorouracil and 5-fluorodeoxyuridine. A new high-pressure liquid chromatographic method for the clinical assay of 5-fluorouracil and 5-fluoroudexyuridine has been developed. The sensitivity and specificity of the method equals that of gas chromatography/mass spectrometric methods. The practical value of the method has been demonstrated by its application in several preliminary clinical studies of 5-fluorouracil in which plasma levels of 10(-8)-10(-6)M were readily monitored."} {"id": "PMID:154359", "title": "Gnotobiotic pigs-derivation and rearing.", "content": "The procurement, rearing, nutrition and microbiological monitoring of gnotobiotic pigs and a method for conditioning of primary, colostrum-deprived, specific pathogen free pigs is described. As compared to the established hysterectomy and closed hysterotomy methods for the derivation of gnotobiotic piglets an alternative approach, open caesarian section with the sow maintained under general halothane-nitrous oxide anaesthesia and the introduction of each fetus into the sterile isolator via a liquid germicidal trap, was found to be more efficient and equally successful in providing viable and microbiologically sterile piglets. Two sterile commercially available milk diets, a special formula for orphan animals and condensed cow's milk, when the latter was supplemented with injectable vitamin E, selenium and iron, proved adequate for satisfactory health of the animals. Two types of pelleted starter rations, sterilized by 4.5 megarads of gamma irradiation, provided adequately for the nutritional needs of older gnotobiotic pigs. Results of microbiological monitoring indicated that the surgical and rearing methods employed were capable of preventing contamination of the animals with bacteria, mycoplasma, yeasts, molds, protozoa and helminths but probably could not exclude occasional vertically transmitted viral infections. Exposure of the animals for four weeks to selected strains of lactobacilli, fecal streptococci and Escherichia coli did not result in visible disease while they were maintained in isolators and conditioned them for transfer into a conventional microbial environment.", "contents": "Gnotobiotic pigs-derivation and rearing. The procurement, rearing, nutrition and microbiological monitoring of gnotobiotic pigs and a method for conditioning of primary, colostrum-deprived, specific pathogen free pigs is described. As compared to the established hysterectomy and closed hysterotomy methods for the derivation of gnotobiotic piglets an alternative approach, open caesarian section with the sow maintained under general halothane-nitrous oxide anaesthesia and the introduction of each fetus into the sterile isolator via a liquid germicidal trap, was found to be more efficient and equally successful in providing viable and microbiologically sterile piglets. Two sterile commercially available milk diets, a special formula for orphan animals and condensed cow's milk, when the latter was supplemented with injectable vitamin E, selenium and iron, proved adequate for satisfactory health of the animals. Two types of pelleted starter rations, sterilized by 4.5 megarads of gamma irradiation, provided adequately for the nutritional needs of older gnotobiotic pigs. Results of microbiological monitoring indicated that the surgical and rearing methods employed were capable of preventing contamination of the animals with bacteria, mycoplasma, yeasts, molds, protozoa and helminths but probably could not exclude occasional vertically transmitted viral infections. Exposure of the animals for four weeks to selected strains of lactobacilli, fecal streptococci and Escherichia coli did not result in visible disease while they were maintained in isolators and conditioned them for transfer into a conventional microbial environment."} {"id": "PMID:154360", "title": "The effects of thymoxamine on anterior chamber depth in human eyes.", "content": "The effects of 0.5% Thymoxamine on intraocular pressure and anterior chamber depth were studied in 20 non-glaucomatous eyes. Miosis occurred in all of the eyes but was not accompanied by a shallowing of the anterior chamber or reduction in the intraocular pressure. The significance of the findings is discussed.", "contents": "The effects of thymoxamine on anterior chamber depth in human eyes. The effects of 0.5% Thymoxamine on intraocular pressure and anterior chamber depth were studied in 20 non-glaucomatous eyes. Miosis occurred in all of the eyes but was not accompanied by a shallowing of the anterior chamber or reduction in the intraocular pressure. The significance of the findings is discussed."} {"id": "PMID:154363", "title": "Phase I trial of chlorozotocin.", "content": "Chlorozotocin was given to 37 patients with advanced malignant tumors in a daily X 5 schedule at 6-week intervals. Total iv doses for each course ranged from 75 to 200 mg/m2. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater or equal to 150 mg/m2; leukopenia occurred only at the highest dose level. Nausea and vomiting were mild and uncommon. No hyperglycemia or adverse drug-related effects on renal or hepatic function were observed. No major antitumor activity occurred; however, three patients with renal cell carcinoma and one patient each with lung cancer, ovarian carcinoma, and Hodgkin's disease had minor objective decreases in tumor size. A dose range of 150--200 mg/m2 iv for each 5-day course is recommended for phase II studies.", "contents": "Phase I trial of chlorozotocin. Chlorozotocin was given to 37 patients with advanced malignant tumors in a daily X 5 schedule at 6-week intervals. Total iv doses for each course ranged from 75 to 200 mg/m2. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater or equal to 150 mg/m2; leukopenia occurred only at the highest dose level. Nausea and vomiting were mild and uncommon. No hyperglycemia or adverse drug-related effects on renal or hepatic function were observed. No major antitumor activity occurred; however, three patients with renal cell carcinoma and one patient each with lung cancer, ovarian carcinoma, and Hodgkin's disease had minor objective decreases in tumor size. A dose range of 150--200 mg/m2 iv for each 5-day course is recommended for phase II studies."} {"id": "PMID:154364", "title": "Capillary density and muscle fibre size in the hearts of rats subjected to stimulated high altitude.", "content": "Six Wistar rats were subjected to a barometric pressure of 50.7 kPa (380 mmHg) for 34 days. These rats and six controls were killed and their myocardial capillaries perfused with India ink. Hypoxia did not induce any proliferation of capillaries in the left ventricle neither did it lead to a reduction in myofibre size. In the right ventricle the capillary density was reduced largely due to a two-fold increase in myofibre area but there was an increase in the capillary: fibre ratio indicating a modest proliferation of capillaries secondary to right ventricular hypertrophy.", "contents": "Capillary density and muscle fibre size in the hearts of rats subjected to stimulated high altitude. Six Wistar rats were subjected to a barometric pressure of 50.7 kPa (380 mmHg) for 34 days. These rats and six controls were killed and their myocardial capillaries perfused with India ink. Hypoxia did not induce any proliferation of capillaries in the left ventricle neither did it lead to a reduction in myofibre size. In the right ventricle the capillary density was reduced largely due to a two-fold increase in myofibre area but there was an increase in the capillary: fibre ratio indicating a modest proliferation of capillaries secondary to right ventricular hypertrophy."} {"id": "PMID:154365", "title": "Radiologic diagnosis of different types of pulmonary stenoses.", "content": "Right ventricular outflow obstructive lesions are among the most prevalent congenital cardiac anomalies with a frequency ranging from 6--10% when considered as isolated anomalies. As part of a more complicated developmental complex, their frequency is undoubtedly higher. The diagnosis can be suspected by the traditional clinical and hemodynamic findings, but a firm diagnosis can only be made by angiography. An exact diagnosis is most important since most of these lesions can be surgically corrected.", "contents": "Radiologic diagnosis of different types of pulmonary stenoses. Right ventricular outflow obstructive lesions are among the most prevalent congenital cardiac anomalies with a frequency ranging from 6--10% when considered as isolated anomalies. As part of a more complicated developmental complex, their frequency is undoubtedly higher. The diagnosis can be suspected by the traditional clinical and hemodynamic findings, but a firm diagnosis can only be made by angiography. An exact diagnosis is most important since most of these lesions can be surgically corrected."} {"id": "PMID:154369", "title": "Middle ear and eustachian tube lining in chronic otitis media.", "content": "By means of histological observations we have tried to find morphological data on which to classify non-suppurative and suppurative chronic otitis media. There was also evidence of pathophysiological features which may have direct influence upon the development and behaviour of chronic inflammations of the tympanic cleft, such as disorders of ventilation and reaction of the mucoperiosteal layer. Local defence mechanisms, the species and virulence of infection also play an important role. It appears that the Eustachian tube is a very effective mechanical and immunological barrier against ascending infection which may perhaps be assisted by antibiotic treatment. Certainly non-suppurative chronic otitis media is more frequent now than in pre-antibiotic days.", "contents": "Middle ear and eustachian tube lining in chronic otitis media. By means of histological observations we have tried to find morphological data on which to classify non-suppurative and suppurative chronic otitis media. There was also evidence of pathophysiological features which may have direct influence upon the development and behaviour of chronic inflammations of the tympanic cleft, such as disorders of ventilation and reaction of the mucoperiosteal layer. Local defence mechanisms, the species and virulence of infection also play an important role. It appears that the Eustachian tube is a very effective mechanical and immunological barrier against ascending infection which may perhaps be assisted by antibiotic treatment. Certainly non-suppurative chronic otitis media is more frequent now than in pre-antibiotic days."} {"id": "PMID:154372", "title": "A comparative trial of two oral cholecystographic contrast media--iocetamic acid (Cholebrin) and iopanoic acid (Telepaque).", "content": "A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measrued in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media.", "contents": "A comparative trial of two oral cholecystographic contrast media--iocetamic acid (Cholebrin) and iopanoic acid (Telepaque). A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measrued in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media."} {"id": "PMID:154373", "title": "Contact allergy in 330 dermatological patients.", "content": "A total of 330 patients with eczematous lesions were tested with 27 topical substances. Among the 88 patients with leg ulcers, 85 (2%) were allergic to one or more substances present in one out of two cases of allergy to wool alcohol. Among the 242 patients suffering from eczematous dermatitis, the percentage of allergic reactions reached 54.6%. A great number of allergic reactions of cetyl alcohol (11.2%), chloramphenicol (10%) and sodium lauryl sulfate (6.4%) was observed. These allergens are not included in the European standard series adopted by the ICDRG. The findings are discussed and compared with data taken from the literature.", "contents": "Contact allergy in 330 dermatological patients. A total of 330 patients with eczematous lesions were tested with 27 topical substances. Among the 88 patients with leg ulcers, 85 (2%) were allergic to one or more substances present in one out of two cases of allergy to wool alcohol. Among the 242 patients suffering from eczematous dermatitis, the percentage of allergic reactions reached 54.6%. A great number of allergic reactions of cetyl alcohol (11.2%), chloramphenicol (10%) and sodium lauryl sulfate (6.4%) was observed. These allergens are not included in the European standard series adopted by the ICDRG. The findings are discussed and compared with data taken from the literature."} {"id": "PMID:154371", "title": "The neuromuscular blocking action of spectinomycin on the mouse hemidiaphragm preparation.", "content": "1. The mechanism of action of the muscle paralysing property of the antibiotic spectinomycin has been investigated on the isolated mouse phrenic nerve-hemidiaphragm preparation. 2. Spectinomycin produced a neuromuscular blockade that was poorly reversed by neostigmine (3 mumol/l) but well reversed by both calcium (5 mmol/l) and 3,4-diaminopyridine (0.1 mmol/l). 3. Intracellular techniques were used to record endplate potentials and miniature endplate potentials from hemidiaphragms paralysed by spectinomycin. Miniature endplate potentials were reduced both in frequency and in amplitude. The quantal content of the endplate potential during spectinomycin paralysis calculated by the method of variance was 14, a value similar to that found in preparations paralysed by the prejunctionally active magnesium. 4. Thus spectinomycin possesses weak neuromuscular blocking activity by a predominant action on acetylcholine release.", "contents": "The neuromuscular blocking action of spectinomycin on the mouse hemidiaphragm preparation. 1. The mechanism of action of the muscle paralysing property of the antibiotic spectinomycin has been investigated on the isolated mouse phrenic nerve-hemidiaphragm preparation. 2. Spectinomycin produced a neuromuscular blockade that was poorly reversed by neostigmine (3 mumol/l) but well reversed by both calcium (5 mmol/l) and 3,4-diaminopyridine (0.1 mmol/l). 3. Intracellular techniques were used to record endplate potentials and miniature endplate potentials from hemidiaphragms paralysed by spectinomycin. Miniature endplate potentials were reduced both in frequency and in amplitude. The quantal content of the endplate potential during spectinomycin paralysis calculated by the method of variance was 14, a value similar to that found in preparations paralysed by the prejunctionally active magnesium. 4. Thus spectinomycin possesses weak neuromuscular blocking activity by a predominant action on acetylcholine release."} {"id": "PMID:154384", "title": "Recently reported causes of contact dermatitis due to synthetic resins and hardeners.", "content": "This study is a survey of recent literature and my own observations concerning dermatological risks of processing and producing plastics. A plea for understanding and cooperation is directed to manufacturers, jurists, occupational physicians, safety engineers, toxicologists, allergologists, dermatologists, industrial and hobby workers, purchasers, consumers and other people involved in order to reach optimal knowledge about risks of processing, warnings and safety procedures.", "contents": "Recently reported causes of contact dermatitis due to synthetic resins and hardeners. This study is a survey of recent literature and my own observations concerning dermatological risks of processing and producing plastics. A plea for understanding and cooperation is directed to manufacturers, jurists, occupational physicians, safety engineers, toxicologists, allergologists, dermatologists, industrial and hobby workers, purchasers, consumers and other people involved in order to reach optimal knowledge about risks of processing, warnings and safety procedures."} {"id": "PMID:154385", "title": "Allergic contact sensitization to the fungicide Maneb.", "content": "Three cases of contact dermatitis caused by Maneb, manganous-ethylene-bis (dithiocarbamate), are described. Maneb is used as an agricultural fungicide, and is also used in spraying solutions in horticulture and in flower shops. Patch testing with Maneb-related compounds revealed no regular pattern of cross sensitization.", "contents": "Allergic contact sensitization to the fungicide Maneb. Three cases of contact dermatitis caused by Maneb, manganous-ethylene-bis (dithiocarbamate), are described. Maneb is used as an agricultural fungicide, and is also used in spraying solutions in horticulture and in flower shops. Patch testing with Maneb-related compounds revealed no regular pattern of cross sensitization."} {"id": "PMID:154386", "title": "Type I allergy from cows in veterinary surgeons.", "content": "Occupational contact dermatitis caused by obstetric work and/or contact with cows is common among veterinary surgeons. We examined serum from nine veterinary surgeons of whom seven gave a history of itching and flare of eczema after obstetric work and/or contact with cows. By means of crossed radioimmunoelectrophoresis the occurrence of specific IgE against cow hair and dander was demonstrated. The IgE did not differ qualitatively or quantitatively from IgE in serum from patients with allergic asthma from cows. Four veterinary surgeons with flare-up of eczema during obstetric aid to cows did not have assignable s-IgE against bovine amnion or allantoic fluids.", "contents": "Type I allergy from cows in veterinary surgeons. Occupational contact dermatitis caused by obstetric work and/or contact with cows is common among veterinary surgeons. We examined serum from nine veterinary surgeons of whom seven gave a history of itching and flare of eczema after obstetric work and/or contact with cows. By means of crossed radioimmunoelectrophoresis the occurrence of specific IgE against cow hair and dander was demonstrated. The IgE did not differ qualitatively or quantitatively from IgE in serum from patients with allergic asthma from cows. Four veterinary surgeons with flare-up of eczema during obstetric aid to cows did not have assignable s-IgE against bovine amnion or allantoic fluids."} {"id": "PMID:154387", "title": "Reduction of chromate in cement by iron sulfate.", "content": "Cement dermatitis is connected with chromate sensitivity. It can therefore be expected that \"elimination\" of chromate in cement would decrease the number of cases of cement dermatitis. Iron sulfate added to cement reduces the chromate completely and the 3-valent chromium is precipitated. An amount of 0.35% (w/w) iron sulfate, FeSO4 . 7H2O, is enough to reduce 20 microgram Cr6+/g cement. There is no technical side effect to the concrete. The iron sulfate is preferably added to cement when there is an intimate contact with skin, e.g. at floor laying, repairs and hand-made casting.", "contents": "Reduction of chromate in cement by iron sulfate. Cement dermatitis is connected with chromate sensitivity. It can therefore be expected that \"elimination\" of chromate in cement would decrease the number of cases of cement dermatitis. Iron sulfate added to cement reduces the chromate completely and the 3-valent chromium is precipitated. An amount of 0.35% (w/w) iron sulfate, FeSO4 . 7H2O, is enough to reduce 20 microgram Cr6+/g cement. There is no technical side effect to the concrete. The iron sulfate is preferably added to cement when there is an intimate contact with skin, e.g. at floor laying, repairs and hand-made casting."} {"id": "PMID:154388", "title": "Contact and microbial allergy in pompholyx.", "content": "Contact sensitivity to medicaments and other chemical allergens has been observed in about 30% of 364 patients with pompholyx. Pompholyx is a recurrent vesicular eruption which increases the incidence of contact sensitivity. The majority of patients tested by means of intradermal and cultural tests did not show any relevant finding on the microbial nature, allergic or not, of pompholyx.", "contents": "Contact and microbial allergy in pompholyx. Contact sensitivity to medicaments and other chemical allergens has been observed in about 30% of 364 patients with pompholyx. Pompholyx is a recurrent vesicular eruption which increases the incidence of contact sensitivity. The majority of patients tested by means of intradermal and cultural tests did not show any relevant finding on the microbial nature, allergic or not, of pompholyx."} {"id": "PMID:154395", "title": "The electrocardiogram in asymmetric septal hypertropy.", "content": "Electrocardiograms and echocardiograms in 44 patients with asymmetric septal hypertrophy were reviewed. Patients with asymmetric septal hypertrophy had incidences of left ventricular hypertrophy (33 percent; 16/44) and left atrial hypertrophy (25 percent; 11/44) by ECG that were less than in a group of patients with significant aortic stenosis (70 percent [31/44] and 64 percent [28/44], respectively). Left ventricular hypertrophy on the ECG was associated with a greater septal-posterior wall thickness ratio in asymmetric septal hypertrophy. A small Q wave in lead V4 or a ratio of the R-wave to the S-wave amplitude (R/S ratio) of greater than 0.20 in lead V1 was found in 14 of 44 patients with asymmetric septal hypertrophy but in no patients with aortic stenosis. The mean corrected Q-T interval (Q-Tc) of patients with asymmetric septal hypertrophy was prolonged, and the mean Q-Tc of patients with aortic stenosis was normal. The distinctive findings of an R/S ratio of more than 0.2 in lead V1 and Q waves in lead V4 in asymmetric septal hypertrophy have clinical significance, and the prolonged Q-T interval may relate to sudden death.", "contents": "The electrocardiogram in asymmetric septal hypertropy. Electrocardiograms and echocardiograms in 44 patients with asymmetric septal hypertrophy were reviewed. Patients with asymmetric septal hypertrophy had incidences of left ventricular hypertrophy (33 percent; 16/44) and left atrial hypertrophy (25 percent; 11/44) by ECG that were less than in a group of patients with significant aortic stenosis (70 percent [31/44] and 64 percent [28/44], respectively). Left ventricular hypertrophy on the ECG was associated with a greater septal-posterior wall thickness ratio in asymmetric septal hypertrophy. A small Q wave in lead V4 or a ratio of the R-wave to the S-wave amplitude (R/S ratio) of greater than 0.20 in lead V1 was found in 14 of 44 patients with asymmetric septal hypertrophy but in no patients with aortic stenosis. The mean corrected Q-T interval (Q-Tc) of patients with asymmetric septal hypertrophy was prolonged, and the mean Q-Tc of patients with aortic stenosis was normal. The distinctive findings of an R/S ratio of more than 0.2 in lead V1 and Q waves in lead V4 in asymmetric septal hypertrophy have clinical significance, and the prolonged Q-T interval may relate to sudden death."} {"id": "PMID:154397", "title": "Comparative neuropsychological study of the changes in different programmed activities in subjects with frontal or retro-rolandic lesions or with Huntington's chorea.", "content": "Eaily performed tests for showing alterations in organization of programmed activities were given to 20 patients with frontal lesions, 23 with retro-rolandic lesions and 17 with Huntington's Chorea. Normal scores were determined in a group of 24 patients without any symptoms of cerebral pathology. The results showed that frontally lesioned patients and those with Huntington's Chorea have similar patterns of disorganization in reproduction of gestures, drawing and rhythmic sound sequences. The data seem to indicate that a major difficulty of these patients lies in faulty \"recall\" of the original model. Retrorolandic patients do not show this difference in response to the differents tests, but have problems in simultaneous organization of visual and auditory information. These results support the hypothesis of LURIA that the frontal lobes regulate programmed motor activity.", "contents": "Comparative neuropsychological study of the changes in different programmed activities in subjects with frontal or retro-rolandic lesions or with Huntington's chorea. Eaily performed tests for showing alterations in organization of programmed activities were given to 20 patients with frontal lesions, 23 with retro-rolandic lesions and 17 with Huntington's Chorea. Normal scores were determined in a group of 24 patients without any symptoms of cerebral pathology. The results showed that frontally lesioned patients and those with Huntington's Chorea have similar patterns of disorganization in reproduction of gestures, drawing and rhythmic sound sequences. The data seem to indicate that a major difficulty of these patients lies in faulty \"recall\" of the original model. Retrorolandic patients do not show this difference in response to the differents tests, but have problems in simultaneous organization of visual and auditory information. These results support the hypothesis of LURIA that the frontal lobes regulate programmed motor activity."} {"id": "PMID:154398", "title": "Biosynthesis of estrogens in pregnant and non-pregnant guinea pigs.", "content": "Guinea pig ovaries obtained from pregnant and non-pregnant animals, incubated in the presence of a NADPH-generating system, converted [3H]-dehydroepiandrosterone and [14C]testosterone to estradiol. Under the same conditions, no radioactive estrogen could be identified in adrenal and placental incubations. The rate of formation of estradiol from dehydroepiandrosterone was linear during the 30-min incubation. The initial rates of formation for estradiol were 415 X 10(-13) and 10.4 X 10(-13) mol/min/g tissue for the ovaries from pregnant and non-pregnant guinea pigs, respectively. The formation of estrone was shown only in the pregnant animal, and the initial rate of formation was 36.0 X 10(-13) mol/min/g tissue. These in vitro studies suggest that the major site of estrogen formation in both pregnant and non-pregnant guinea pigs is the ovary.", "contents": "Biosynthesis of estrogens in pregnant and non-pregnant guinea pigs. Guinea pig ovaries obtained from pregnant and non-pregnant animals, incubated in the presence of a NADPH-generating system, converted [3H]-dehydroepiandrosterone and [14C]testosterone to estradiol. Under the same conditions, no radioactive estrogen could be identified in adrenal and placental incubations. The rate of formation of estradiol from dehydroepiandrosterone was linear during the 30-min incubation. The initial rates of formation for estradiol were 415 X 10(-13) and 10.4 X 10(-13) mol/min/g tissue for the ovaries from pregnant and non-pregnant guinea pigs, respectively. The formation of estrone was shown only in the pregnant animal, and the initial rate of formation was 36.0 X 10(-13) mol/min/g tissue. These in vitro studies suggest that the major site of estrogen formation in both pregnant and non-pregnant guinea pigs is the ovary."} {"id": "PMID:154400", "title": "Isolation and characterization of fragments of reduced and S-carbamidomethylated human growth hormone produced by plasmin digestion. I. Chemistry.", "content": "Reduced and S-carbamidomethylated human GH (RCAM-hGH) was digested with human plasmin, yielding a mixture of products. These were partially separated by chromatography on DEAE-cellulose, yielding three major fractions: Da and Db, which were equipotent with native hGH in the weight gain test; and Dc, which was about half as active as hGH. Each of these was further purified by gel filtration, yielding a number of subfractions which were characterized as follows: Da1 is a very stable noncovalent complex of residues 1--134 and 141--191 of RCAM-hGH; Da2 represents residues 20--41; Db1 is very similar to Da1, but appears to have lost one or more amide groups; Db3 represents residues 95--134; Dc2 is a heterogenous fraction containing a further deamidated version of Da1 and Db1 plus a similar complex of residues 42--134 and 141--191, apparently with some carboxyterminal heterogeneity; Dc3, like Db3, represents residues 95--134. The biological activities of these fragments are discussed in the accompanying paper. Earlier work has shown that native hGH, upon digestion with plasmin, is cleaved primarily at residues 134 and 140. It is shown here that when RCAM-hGH is digested with plasmin, in about 87% of the molecules at least one cleavage takes place in addition to those at residues 134 and 140.", "contents": "Isolation and characterization of fragments of reduced and S-carbamidomethylated human growth hormone produced by plasmin digestion. I. Chemistry. Reduced and S-carbamidomethylated human GH (RCAM-hGH) was digested with human plasmin, yielding a mixture of products. These were partially separated by chromatography on DEAE-cellulose, yielding three major fractions: Da and Db, which were equipotent with native hGH in the weight gain test; and Dc, which was about half as active as hGH. Each of these was further purified by gel filtration, yielding a number of subfractions which were characterized as follows: Da1 is a very stable noncovalent complex of residues 1--134 and 141--191 of RCAM-hGH; Da2 represents residues 20--41; Db1 is very similar to Da1, but appears to have lost one or more amide groups; Db3 represents residues 95--134; Dc2 is a heterogenous fraction containing a further deamidated version of Da1 and Db1 plus a similar complex of residues 42--134 and 141--191, apparently with some carboxyterminal heterogeneity; Dc3, like Db3, represents residues 95--134. The biological activities of these fragments are discussed in the accompanying paper. Earlier work has shown that native hGH, upon digestion with plasmin, is cleaved primarily at residues 134 and 140. It is shown here that when RCAM-hGH is digested with plasmin, in about 87% of the molecules at least one cleavage takes place in addition to those at residues 134 and 140."} {"id": "PMID:154402", "title": "Changes in somatostatin concentration in pancreas and other tissues of streptozotocin diabetic rats.", "content": "Changes in immunoreactive somatostatin were examined in islets, whole pancreas, stomach, and hypothalamus of streptozotocin-diabetic rats. There was no change in islet somatostatin content at 2 days after the administration of streptozotocin, but thereafter, somatostatin progressively increased in the diabetic animals by 45% at 2 weeks, 230% at 6 weeks, and 500% by 6 months. By contrast, islet glucagon rose acutely and maintained a constant 2-fold elevation irrespective of the duration of the diabetes. Morphometric analysis of the somatostatin- and glucagon-producing cells in the islets revealed an apparent augmentation of both cell types. The concentration of somatostatin per total pancreas was also increased in the diabetic animals, suggesting that the islet increase was part of a true increase in pancreatic somatostatin. Pancreatic glucagon was unchanged despite the islet increase. The increase in pancreatic somatostatin was paralleled by an elevation in gastric somatostatin concentration, implying a common mechanism in response to streptozotocin for the somatostatin cells in these two sites. There was no change in hypothalamic somatostatin concentration. Islet somatostatin was also increased in alloxan-diabetic rats. suggesting that streptozotocin does not stimulate the D cells directly.", "contents": "Changes in somatostatin concentration in pancreas and other tissues of streptozotocin diabetic rats. Changes in immunoreactive somatostatin were examined in islets, whole pancreas, stomach, and hypothalamus of streptozotocin-diabetic rats. There was no change in islet somatostatin content at 2 days after the administration of streptozotocin, but thereafter, somatostatin progressively increased in the diabetic animals by 45% at 2 weeks, 230% at 6 weeks, and 500% by 6 months. By contrast, islet glucagon rose acutely and maintained a constant 2-fold elevation irrespective of the duration of the diabetes. Morphometric analysis of the somatostatin- and glucagon-producing cells in the islets revealed an apparent augmentation of both cell types. The concentration of somatostatin per total pancreas was also increased in the diabetic animals, suggesting that the islet increase was part of a true increase in pancreatic somatostatin. Pancreatic glucagon was unchanged despite the islet increase. The increase in pancreatic somatostatin was paralleled by an elevation in gastric somatostatin concentration, implying a common mechanism in response to streptozotocin for the somatostatin cells in these two sites. There was no change in hypothalamic somatostatin concentration. Islet somatostatin was also increased in alloxan-diabetic rats. suggesting that streptozotocin does not stimulate the D cells directly."} {"id": "PMID:154403", "title": "Sex differences in the multiple-dose streptozotocin model of diabetes.", "content": "The hyperglycemic response to multiple low-dose SZ injections was measured in castrated and non-castrated male and female mice with or without testosterone treatment. On the 10th day of the experiment, control males had plasma glucose concentrations that were significantly higher than those of control females. Castration of males decreased the hyperglycemic response, while testosterone treatment restored it. The glucose concentrations in castrated females were significantly greater than control females, but not different from castrated males. Testosterone administration to castrated or non-castrated females increased the hyperglycemic response to that seen in control males and in testosterone-treated castrated males. Thus, castration negates the sex difference in the hyperglycemic response to the multiple low-dose SZ injections. Testosterone enhances the hyperglycemic response in castrated or non-castrated females, and in castrated males.", "contents": "Sex differences in the multiple-dose streptozotocin model of diabetes. The hyperglycemic response to multiple low-dose SZ injections was measured in castrated and non-castrated male and female mice with or without testosterone treatment. On the 10th day of the experiment, control males had plasma glucose concentrations that were significantly higher than those of control females. Castration of males decreased the hyperglycemic response, while testosterone treatment restored it. The glucose concentrations in castrated females were significantly greater than control females, but not different from castrated males. Testosterone administration to castrated or non-castrated females increased the hyperglycemic response to that seen in control males and in testosterone-treated castrated males. Thus, castration negates the sex difference in the hyperglycemic response to the multiple low-dose SZ injections. Testosterone enhances the hyperglycemic response in castrated or non-castrated females, and in castrated males."} {"id": "PMID:154404", "title": "Molecular transformations in sarcoplasmic reticulum of fast-twitch muscle by electro-stimulation.", "content": "Chronic electro-stimulation of fast-twitch rabbit muscle with the frequency pattern received by a slow-twitch muscle induces a progressive transformation of the sarcoplasmic reticulum. After 2 days stimulation activities of Ca2+-dependent ATPase and of Ca2+ transport begin to decrease, and are paralleled by a progressive decrease in Ca2+-dependent and Ca2+, Mg2+-dependent phosphoprotein formation, reduced rate of dephosphorylation and a rearrangement of the electrophoretic polypeptide and phosphoprotein patterns. These findings suggest a transformation of the sarcoplasmic reticulum to resemble that of a slow-twitch muscle. This transformation is paralleled by increase in time-to-peak of twitch contraction and half relaxation time and occurs before conversion of the myosin light chain pattern is observed. The parallel time course of changes in contractile properties of stimulated muscle and the molecular and functional properties of the sarcoplasmic reticulum emphasizes the definitive role of the latter in determining the twitch characteristics of fast and slow twitch muscles.", "contents": "Molecular transformations in sarcoplasmic reticulum of fast-twitch muscle by electro-stimulation. Chronic electro-stimulation of fast-twitch rabbit muscle with the frequency pattern received by a slow-twitch muscle induces a progressive transformation of the sarcoplasmic reticulum. After 2 days stimulation activities of Ca2+-dependent ATPase and of Ca2+ transport begin to decrease, and are paralleled by a progressive decrease in Ca2+-dependent and Ca2+, Mg2+-dependent phosphoprotein formation, reduced rate of dephosphorylation and a rearrangement of the electrophoretic polypeptide and phosphoprotein patterns. These findings suggest a transformation of the sarcoplasmic reticulum to resemble that of a slow-twitch muscle. This transformation is paralleled by increase in time-to-peak of twitch contraction and half relaxation time and occurs before conversion of the myosin light chain pattern is observed. The parallel time course of changes in contractile properties of stimulated muscle and the molecular and functional properties of the sarcoplasmic reticulum emphasizes the definitive role of the latter in determining the twitch characteristics of fast and slow twitch muscles."} {"id": "PMID:154405", "title": "The dicyclohexylcarbodiimide-binding protein of the mitochondrial ATPase complex from Neurospora crassa and Saccharomyces cerevisiae. Identification and isolation.", "content": "Incubation of mitochondria from Neurospora crassa and Saccharomyces cerevisiae with the radioactive ATPase inhibitor [14C]dicyclohexylcarbodiimide results in the irreversible and rather specific labelling of a low-molecular-weight polypeptide. This dicyclohexylcarbodiimide-binding protein is identical with the smallest subunit (Mr 8000) of the mitochondrial ATPase complex, and it occurs as oligomer, probably as hexamer, in the enzyme protein. The dicyclohexylcarbodiimide-binding protein is extracted from whole mitochondria with neutral chloroform/methanol both in the free and in the inhibitor-modified form. In Neurospora and yeast, this extraction is highly selective and the protein is obtained in homogeneous form when the mitochondria have been prewashed with certain organic solvents. The bound dicyclohexylcarbodiimide label is enriched in the purified protein up to 50-fold compared to whole mitochondria. Based on the amino acid analysis, the dicyclohexylcarbodiimide-binding protein from Neurospora and yeast consists of at least 81 and 76 residues, respectively. The content of hydrophobic residues is extremely high. Histidine and tryptophan are absent. The N-terminal amino acid is tyrosine in Neurospora and formylmethionine in yeast.", "contents": "The dicyclohexylcarbodiimide-binding protein of the mitochondrial ATPase complex from Neurospora crassa and Saccharomyces cerevisiae. Identification and isolation. Incubation of mitochondria from Neurospora crassa and Saccharomyces cerevisiae with the radioactive ATPase inhibitor [14C]dicyclohexylcarbodiimide results in the irreversible and rather specific labelling of a low-molecular-weight polypeptide. This dicyclohexylcarbodiimide-binding protein is identical with the smallest subunit (Mr 8000) of the mitochondrial ATPase complex, and it occurs as oligomer, probably as hexamer, in the enzyme protein. The dicyclohexylcarbodiimide-binding protein is extracted from whole mitochondria with neutral chloroform/methanol both in the free and in the inhibitor-modified form. In Neurospora and yeast, this extraction is highly selective and the protein is obtained in homogeneous form when the mitochondria have been prewashed with certain organic solvents. The bound dicyclohexylcarbodiimide label is enriched in the purified protein up to 50-fold compared to whole mitochondria. Based on the amino acid analysis, the dicyclohexylcarbodiimide-binding protein from Neurospora and yeast consists of at least 81 and 76 residues, respectively. The content of hydrophobic residues is extremely high. Histidine and tryptophan are absent. The N-terminal amino acid is tyrosine in Neurospora and formylmethionine in yeast."} {"id": "PMID:154406", "title": "Histochemical and ultrastructural findings in a case of centronuclear myopathy.", "content": "A case of centronuclear myopathy is presented. The presence of central nuclei in almost all fibres, the existence of type I fibres only, the histochemical pattern of a negative central zone with a perinuclear halo and a hyperactive rim with oxidative enzymes and the ultrastructural data are discussed in the light of the previous literature. The possible relationships with other myopathies are taken into consideration as well as the fact that central nuclei may be a non-specific change in several conditions. Consequently centronuclear myopathy could turn out to be a syndrome from which different entities can be isolated.", "contents": "Histochemical and ultrastructural findings in a case of centronuclear myopathy. A case of centronuclear myopathy is presented. The presence of central nuclei in almost all fibres, the existence of type I fibres only, the histochemical pattern of a negative central zone with a perinuclear halo and a hyperactive rim with oxidative enzymes and the ultrastructural data are discussed in the light of the previous literature. The possible relationships with other myopathies are taken into consideration as well as the fact that central nuclei may be a non-specific change in several conditions. Consequently centronuclear myopathy could turn out to be a syndrome from which different entities can be isolated."} {"id": "PMID:154407", "title": "A case of persistent atrial standstill.", "content": "A case of persistent atrial standstill is described. The criteria for diagnosing atrial standstill are separated into two categories: the lack of electrical atrial activity and the lack of mechanical atrial activity. Echocardiography of the anterior mitral leaflet is to be used as one of the noninvasive methods for the diagnosis of the lack of mechanical atrial activity.", "contents": "A case of persistent atrial standstill. A case of persistent atrial standstill is described. The criteria for diagnosing atrial standstill are separated into two categories: the lack of electrical atrial activity and the lack of mechanical atrial activity. Echocardiography of the anterior mitral leaflet is to be used as one of the noninvasive methods for the diagnosis of the lack of mechanical atrial activity."} {"id": "PMID:154410", "title": "Ultrastructure of muscle spindles in C57BL/6J dy2J/dy2J dystrophic mice.", "content": "The sensory organs of skeletal muscles, the muscle spindles, were examined using electron microscopy in dy2J/dy2J dystrophic mice. Despite widespread damage to the extrafusal (skeletomotor) fibres the intrafusal (spindle) fibres appeared normal and seemed resistant to the aetiological factors for murine dystrophy.", "contents": "Ultrastructure of muscle spindles in C57BL/6J dy2J/dy2J dystrophic mice. The sensory organs of skeletal muscles, the muscle spindles, were examined using electron microscopy in dy2J/dy2J dystrophic mice. Despite widespread damage to the extrafusal (skeletomotor) fibres the intrafusal (spindle) fibres appeared normal and seemed resistant to the aetiological factors for murine dystrophy."} {"id": "PMID:154411", "title": "Rheological properties of human blood plasma--a comparison of measurements with three different viscometers.", "content": "Human plasma viscosity was measured in capillary tube, cone-plate and Couette viscometers. The measurement of the viscosity at very low shear rates showed that plasma is a non-Newtonian fluid with a pseudoplastic rheological behaviour. The importance of this phenomenon for the microcirculation is discussed.", "contents": "Rheological properties of human blood plasma--a comparison of measurements with three different viscometers. Human plasma viscosity was measured in capillary tube, cone-plate and Couette viscometers. The measurement of the viscosity at very low shear rates showed that plasma is a non-Newtonian fluid with a pseudoplastic rheological behaviour. The importance of this phenomenon for the microcirculation is discussed."} {"id": "PMID:154412", "title": "A simple technique for testing the in vitro response of rabbit lymphocytes to PHA and allogeneic cells.", "content": "Lymphocytes of rabbits can be separated from small quantities of heparinized whole blood using a simple density gradient of Ficoll-Ronpacon 1.09. This separation technique yields a pure suspension of viable cells allowing reproducible results from cultures stimulated either with PHA or allogeneic lymphocytes isolated by the same technique.", "contents": "A simple technique for testing the in vitro response of rabbit lymphocytes to PHA and allogeneic cells. Lymphocytes of rabbits can be separated from small quantities of heparinized whole blood using a simple density gradient of Ficoll-Ronpacon 1.09. This separation technique yields a pure suspension of viable cells allowing reproducible results from cultures stimulated either with PHA or allogeneic lymphocytes isolated by the same technique."} {"id": "PMID:154414", "title": "[Tricyclic homologs of piperazine. III. Synthesis of 4-substituted hexahydro-1H-2,6-methanopyrrolo[1,2a]pyrazines].", "content": "The Authors describe the synthesis of some quaternary salts of the hexahydro-1H-2,6-methanopyrrolo[1,2-a]pyrazines mono or disubstituted at carbon-4. These were obtained directly by cyclization of the corresponding diazabicyclooctanes, by formation of a substituted ethylenic bridge between the two nitrogen atoms. The compounds were pharmacologically screened; the hypothesis of enhancement of curare-like activity in comparison with the unsubstituted derivatives was not confirmed.", "contents": "[Tricyclic homologs of piperazine. III. Synthesis of 4-substituted hexahydro-1H-2,6-methanopyrrolo[1,2a]pyrazines]. The Authors describe the synthesis of some quaternary salts of the hexahydro-1H-2,6-methanopyrrolo[1,2-a]pyrazines mono or disubstituted at carbon-4. These were obtained directly by cyclization of the corresponding diazabicyclooctanes, by formation of a substituted ethylenic bridge between the two nitrogen atoms. The compounds were pharmacologically screened; the hypothesis of enhancement of curare-like activity in comparison with the unsubstituted derivatives was not confirmed."} {"id": "PMID:154413", "title": "[Effect of beryllium salts on the activity of sarcoplasmic reticulum Ca2+,Mg2+-dependent ATP-ase].", "content": "In the presence of Mg2+ and Ca2+ ions beryllium compounds inhibit the Ca2+, Mg2+-dependent ATPase activity and the transport of Ca2+ in the sarcoplasmatic reticulum vesicles. The inhibition is reversible and concurrent with respect to the Mg2+ ions. In the absence of the Mg2+ ions an addition of beryllium compounds stimulates the ATPase activity, the dependence of the degree of its stimulation on the beryllium compounds concentration is characterized by a curve with a maximum. On the membranous Ca2+, Mg2+-dependent ATPase preparations beryllium compounds produce a stronger inhibiting effect than in the case of the purified enzyme, which is, apparently, due to their ability to influence the membranous structure. The hydrophobic spin probe method shows that beryllium compounds reduce the microviscosity of the lipid sections of the membrane.", "contents": "[Effect of beryllium salts on the activity of sarcoplasmic reticulum Ca2+,Mg2+-dependent ATP-ase]. In the presence of Mg2+ and Ca2+ ions beryllium compounds inhibit the Ca2+, Mg2+-dependent ATPase activity and the transport of Ca2+ in the sarcoplasmatic reticulum vesicles. The inhibition is reversible and concurrent with respect to the Mg2+ ions. In the absence of the Mg2+ ions an addition of beryllium compounds stimulates the ATPase activity, the dependence of the degree of its stimulation on the beryllium compounds concentration is characterized by a curve with a maximum. On the membranous Ca2+, Mg2+-dependent ATPase preparations beryllium compounds produce a stronger inhibiting effect than in the case of the purified enzyme, which is, apparently, due to their ability to influence the membranous structure. The hydrophobic spin probe method shows that beryllium compounds reduce the microviscosity of the lipid sections of the membrane."} {"id": "PMID:154426", "title": "Oxamethacin: a pilot field survey.", "content": "Two hundred sixty-four general practice patients were treated with oxamethacin (100 mg b.i.d.) and 261 with indomethacin (50 mg b.i.d.) for a maximum period of two weeks. Both drugs showed equally good analgesic and anti-inflammatory effects. Thirty-six patients (14%) treated with oxamethacin and sixty patients (23%) treated with indomethacin reported side-effects. Among them, seventeen patients on oxamethacin (6%) and forty-tree patients on indomethacin (16.5%) reported gastro-intestinal disorders. Side-effects necessitated interruption of treatment in fourteen patients (5%) on oxamethacin and in thirty-three patients (13%) on indomethacin.", "contents": "Oxamethacin: a pilot field survey. Two hundred sixty-four general practice patients were treated with oxamethacin (100 mg b.i.d.) and 261 with indomethacin (50 mg b.i.d.) for a maximum period of two weeks. Both drugs showed equally good analgesic and anti-inflammatory effects. Thirty-six patients (14%) treated with oxamethacin and sixty patients (23%) treated with indomethacin reported side-effects. Among them, seventeen patients on oxamethacin (6%) and forty-tree patients on indomethacin (16.5%) reported gastro-intestinal disorders. Side-effects necessitated interruption of treatment in fourteen patients (5%) on oxamethacin and in thirty-three patients (13%) on indomethacin."} {"id": "PMID:154428", "title": "[Regeneration of the Fallopian tubes following sterilization (author's transl)].", "content": "After any trauma to the fallopian tubes by a sterilizing operation, pregnancy occurs. If the sterilizing procedure was by high frequency current coagulation, large areas of the fallopian tube must be destroyed down into the mesosalpinx in order to avoid the preprogrammed recanalization tendency of the muellerian duct. Fertilization has occurred in recanalized fallopian tubes which only showed a cubic epithelium. Extensive destruction of the fallopian tube is today not justifiable because of the possibility of interference with the ovarian blood supply and subsequent hormonal damage. At present the safest method of female sterilization is by tissue coagulation of segment of the fallopian tube at 100 centigrade and division of the coagulated portion. In 1000 cases there were no pregnancies.", "contents": "[Regeneration of the Fallopian tubes following sterilization (author's transl)]. After any trauma to the fallopian tubes by a sterilizing operation, pregnancy occurs. If the sterilizing procedure was by high frequency current coagulation, large areas of the fallopian tube must be destroyed down into the mesosalpinx in order to avoid the preprogrammed recanalization tendency of the muellerian duct. Fertilization has occurred in recanalized fallopian tubes which only showed a cubic epithelium. Extensive destruction of the fallopian tube is today not justifiable because of the possibility of interference with the ovarian blood supply and subsequent hormonal damage. At present the safest method of female sterilization is by tissue coagulation of segment of the fallopian tube at 100 centigrade and division of the coagulated portion. In 1000 cases there were no pregnancies."} {"id": "PMID:154429", "title": "[Medical genetic study of the population of Uzbekistan. V. The frequency of heterozygous beta-thalassemia in 4 kishlaks of Urgut District, Samarkand Province].", "content": "A subject of this investigation is the results of the subtotal examination of 4 villages for the detection of heterozygous beta-thalassemic carriers. 848 persons (55.5% of the registered population) have been examined. The mean frequency of the beta-Th gene was 0.0159, FST-Wahlund--0.00975. Statistically significant differences in the gene frequencies between villages have been revealed (p less than 0.01). The study of genetic distances (by Edwards) has revealed no intertribe differences in gene frequencies. The comparison of findings of the present study with other similar investigations enabled to account for the detected differences in the frequencies of beta-thalassemia as a result of the genetic drift. The importance of choosing populations for the study and methods for detection heterozygous beta-thalassemia are discussed.", "contents": "[Medical genetic study of the population of Uzbekistan. V. The frequency of heterozygous beta-thalassemia in 4 kishlaks of Urgut District, Samarkand Province]. A subject of this investigation is the results of the subtotal examination of 4 villages for the detection of heterozygous beta-thalassemic carriers. 848 persons (55.5% of the registered population) have been examined. The mean frequency of the beta-Th gene was 0.0159, FST-Wahlund--0.00975. Statistically significant differences in the gene frequencies between villages have been revealed (p less than 0.01). The study of genetic distances (by Edwards) has revealed no intertribe differences in gene frequencies. The comparison of findings of the present study with other similar investigations enabled to account for the detected differences in the frequencies of beta-thalassemia as a result of the genetic drift. The importance of choosing populations for the study and methods for detection heterozygous beta-thalassemia are discussed."} {"id": "PMID:154430", "title": "Transcription and translation in E. coli of hybrid plasmids containing the catabolic dehydroquinase gene from Neurospora crassa.", "content": "Two hybrid plasmids which carry the gene for Neurospora crassa catabolic dehydroquinase (C-DHQase) and complement an aroD6 (dehydroquinase-deficient) auxotroph of Escherichia coli have been analyzed. One of these contains a 2.9 kilobase (kb) fragment cloned in the HindIII site of plasmid pBR322 (pVK57) and the other contains a 6.8 kb fragment cloned in the PstI site (pVK88). Restriction enzyme mapping of these plasmids has demonstrated that the 2.9 kb fragment is totally contained within the 6.8 kb fragment. When the polarity of either the HindIII fragment or PstI fragment was reversed with respect to pBR322 no effect was observed on either the ability of the hybrid to complement an aroD- auxotroph or on the level of C-DHQase activity. In vivo transcription of plasmid pVK88 in both orientations was analyzed by RNA-DNA hybridization and by the techniques developed by Southern (1975). Approx. 40% of the plasmid-directed transcription occurred from the cloned PstI fragment and 60--70% of these N. crassa transcripts were encoded by the 2.9 kb HindIII fragment. The Southern technique allowed a further localization of the region of most extensive transcription to a 1.8 kb HindIII-EcoRI fragment. Biochemical analysis revealed that the C-DHQase protein produced by strains harboring pVK57 and pVK88 in either orientation was identical to the N. crassa enzyme. Furthermore, when these plasmids were segregated into minicells and labeled with 14C amino acids, the C-DHQase protein was synthesized at a level comparable to other plasmid-encoded proteins. Taken together, these experiments demonstrate that transcription is efficiently initiated in E. coli from a site on the cloned N. crassa DNA and that the resulting C-DHQase mRNA is efficiently and accurately translated.", "contents": "Transcription and translation in E. coli of hybrid plasmids containing the catabolic dehydroquinase gene from Neurospora crassa. Two hybrid plasmids which carry the gene for Neurospora crassa catabolic dehydroquinase (C-DHQase) and complement an aroD6 (dehydroquinase-deficient) auxotroph of Escherichia coli have been analyzed. One of these contains a 2.9 kilobase (kb) fragment cloned in the HindIII site of plasmid pBR322 (pVK57) and the other contains a 6.8 kb fragment cloned in the PstI site (pVK88). Restriction enzyme mapping of these plasmids has demonstrated that the 2.9 kb fragment is totally contained within the 6.8 kb fragment. When the polarity of either the HindIII fragment or PstI fragment was reversed with respect to pBR322 no effect was observed on either the ability of the hybrid to complement an aroD- auxotroph or on the level of C-DHQase activity. In vivo transcription of plasmid pVK88 in both orientations was analyzed by RNA-DNA hybridization and by the techniques developed by Southern (1975). Approx. 40% of the plasmid-directed transcription occurred from the cloned PstI fragment and 60--70% of these N. crassa transcripts were encoded by the 2.9 kb HindIII fragment. The Southern technique allowed a further localization of the region of most extensive transcription to a 1.8 kb HindIII-EcoRI fragment. Biochemical analysis revealed that the C-DHQase protein produced by strains harboring pVK57 and pVK88 in either orientation was identical to the N. crassa enzyme. Furthermore, when these plasmids were segregated into minicells and labeled with 14C amino acids, the C-DHQase protein was synthesized at a level comparable to other plasmid-encoded proteins. Taken together, these experiments demonstrate that transcription is efficiently initiated in E. coli from a site on the cloned N. crassa DNA and that the resulting C-DHQase mRNA is efficiently and accurately translated."} {"id": "PMID:154438", "title": "[Effects of a new psychotropic agent, CS-430, on the central nervous system of experimental animals (author's transl)].", "content": "In rats and rabbits with chronically implanted electrodes CS-430(10-bromo-2, 3, 7, 11b-tetrahydro--11b-(2-fluorophenyl)-oxazolo(3, 2d) [1, 4]benzodiazepine-6(5H)-one) (3 mg/kg, .o.) decreased the slightly awake period and increased the slow-wave sleep period. The onset time of sleep was significantly shortened. In the rat pre-treated with p-chlorophenylalaine (500 mg/kg, p.o.), the awake period was remarkable increased and the slow wave sleep period was considerably decreased at 48 hours after the pre-treatment. In these rats CS-430 given in the same dose decreased significantly the awake peiod and the onset time of sleep and increased the slow wave sleep period. CS-430 raised the threshold of the arousal response with stimulation of the posterior hypothalamus, but not of the mesencephalic reticular formation. These effects of CS-430 were almost as potent as those of nitrazepam (NZP). CS-430 reduced duration of after-discharges following stimulation of the hippocampus, depressed the decerebrate rigidity and inhibited activity of lumbar gamma-motoneurons in anesthetized cats. CS-430 (10 mg/kg, p.o.) inhibited the evoked responses recorded from the proreus gyrus following stimulation of either the baso-magnocellularis of the amygdaloid nuclear or the ventral hippocampus, although such did not inhibit the responses between the olfactory bulb and the pyriform cortex, the thalamus and the sensory-motor cortex. Thus CS-430 has a sleep-inducing effect in animals of almost the same potency as is seen with NZP, and site(s) of the action in the limbic system appear to be specific.", "contents": "[Effects of a new psychotropic agent, CS-430, on the central nervous system of experimental animals (author's transl)]. In rats and rabbits with chronically implanted electrodes CS-430(10-bromo-2, 3, 7, 11b-tetrahydro--11b-(2-fluorophenyl)-oxazolo(3, 2d) [1, 4]benzodiazepine-6(5H)-one) (3 mg/kg, .o.) decreased the slightly awake period and increased the slow-wave sleep period. The onset time of sleep was significantly shortened. In the rat pre-treated with p-chlorophenylalaine (500 mg/kg, p.o.), the awake period was remarkable increased and the slow wave sleep period was considerably decreased at 48 hours after the pre-treatment. In these rats CS-430 given in the same dose decreased significantly the awake peiod and the onset time of sleep and increased the slow wave sleep period. CS-430 raised the threshold of the arousal response with stimulation of the posterior hypothalamus, but not of the mesencephalic reticular formation. These effects of CS-430 were almost as potent as those of nitrazepam (NZP). CS-430 reduced duration of after-discharges following stimulation of the hippocampus, depressed the decerebrate rigidity and inhibited activity of lumbar gamma-motoneurons in anesthetized cats. CS-430 (10 mg/kg, p.o.) inhibited the evoked responses recorded from the proreus gyrus following stimulation of either the baso-magnocellularis of the amygdaloid nuclear or the ventral hippocampus, although such did not inhibit the responses between the olfactory bulb and the pyriform cortex, the thalamus and the sensory-motor cortex. Thus CS-430 has a sleep-inducing effect in animals of almost the same potency as is seen with NZP, and site(s) of the action in the limbic system appear to be specific."} {"id": "PMID:154442", "title": "[Roentgenological differention of intrapulmonary findings in patients with hodgkin's disease (author's transl)].", "content": "The spectrum of intrapulmonary findings of Hodgkin's disease is illustrated by 75 pulmonary episodes of 22 patients with Hodgkin's disease (duration of illness up to 14 years). Both the typical and frequent, as well as the rare pulmonary manifestations are discussed. We analysed the time correlation between pulmonary changes and clinical manifestations, and the effect of therapy. This retrospective investigation showed that more than 55% of the observed 75 pulmonary episodes have been diagnosed correctly by the initial radiological examination. By simultaneous appearance of different forms of disease propagation, sideeffect of therapy and superimposed diseases, diagnosis may be impaired.", "contents": "[Roentgenological differention of intrapulmonary findings in patients with hodgkin's disease (author's transl)]. The spectrum of intrapulmonary findings of Hodgkin's disease is illustrated by 75 pulmonary episodes of 22 patients with Hodgkin's disease (duration of illness up to 14 years). Both the typical and frequent, as well as the rare pulmonary manifestations are discussed. We analysed the time correlation between pulmonary changes and clinical manifestations, and the effect of therapy. This retrospective investigation showed that more than 55% of the observed 75 pulmonary episodes have been diagnosed correctly by the initial radiological examination. By simultaneous appearance of different forms of disease propagation, sideeffect of therapy and superimposed diseases, diagnosis may be impaired."} {"id": "PMID:154443", "title": "[Roentgenological aspects of the cyst lung in newborn (author's transl)].", "content": "The article reports on the angiographic identification of a cyst lung in a newborn with special consideration of the differential diagnostic differentiation from lung sequestration which appears similar in the full size radiograph. The article also discusses further differential diagnoses, complications and treatment possibilities of cyst lungs.", "contents": "[Roentgenological aspects of the cyst lung in newborn (author's transl)]. The article reports on the angiographic identification of a cyst lung in a newborn with special consideration of the differential diagnostic differentiation from lung sequestration which appears similar in the full size radiograph. The article also discusses further differential diagnoses, complications and treatment possibilities of cyst lungs."} {"id": "PMID:154444", "title": "[Computer tomography in the diagnosis of aortic aneurysms (author's transl)].", "content": "The paper describes the diagnosis of ten thoracic, 20 abdominal and three peripheral arterial aneurysms by computer tomography. This permits a definite diagnosis by a non-invasive method, it defines the extent of the aneurysm and the amount of thrombus in the aneurysm; it permits recognition of a leak and is painless and without risk and can be performed rapidly. Morever, computer tomography provides an accurate control of growth of the aneurysm. In some cases a dissection can be recognised. The use of adequate quantities of intravenous contrast medium prevents any possibility of an incorrect diagnosis. The extent and density of the aneurysms, their lumina, clot and wall thickness, as determined by computer tomography are described. The values are compared with the aortic diameters of patients with normal vessels. The advantages of the method, compared with other procedures, are discussed and its role in the diagnosis of aortic and peripheral arterial aneurysms is described.", "contents": "[Computer tomography in the diagnosis of aortic aneurysms (author's transl)]. The paper describes the diagnosis of ten thoracic, 20 abdominal and three peripheral arterial aneurysms by computer tomography. This permits a definite diagnosis by a non-invasive method, it defines the extent of the aneurysm and the amount of thrombus in the aneurysm; it permits recognition of a leak and is painless and without risk and can be performed rapidly. Morever, computer tomography provides an accurate control of growth of the aneurysm. In some cases a dissection can be recognised. The use of adequate quantities of intravenous contrast medium prevents any possibility of an incorrect diagnosis. The extent and density of the aneurysms, their lumina, clot and wall thickness, as determined by computer tomography are described. The values are compared with the aortic diameters of patients with normal vessels. The advantages of the method, compared with other procedures, are discussed and its role in the diagnosis of aortic and peripheral arterial aneurysms is described."} {"id": "PMID:154445", "title": "[Early and late results of 131I treatment of benign goitres in an endemic area in southern bavaria (author's transl)].", "content": "Following the application of 10 000 to 15 000 rd, to 471 patients with benign goitres, mechanical symptoms were relieved in 72 to 82% during a course of six follow-up examinations; the circumference of the neck was reduced by 1.2 to 1.6 cm., the scintigraphic area by 9 to 31% and maximal 131I uptake was reduced by 18 to 31%. Follow-up examinations at 6.4 and 5.5 years in 155 patients showed the best regression of neck circumference (2.2 to 2.6 cm.) and of the area of the scintigram (28 to 31%). 50% of the patients had had recurrences from previous goitre removals and 1 to 3% developed post-therapeutic hypothyroidism. There was no significant change in the level of the peripheral thyroid hormones following treatment, but 10 to 20% were within the hypothyroid range for the area of iodine deficiency.", "contents": "[Early and late results of 131I treatment of benign goitres in an endemic area in southern bavaria (author's transl)]. Following the application of 10 000 to 15 000 rd, to 471 patients with benign goitres, mechanical symptoms were relieved in 72 to 82% during a course of six follow-up examinations; the circumference of the neck was reduced by 1.2 to 1.6 cm., the scintigraphic area by 9 to 31% and maximal 131I uptake was reduced by 18 to 31%. Follow-up examinations at 6.4 and 5.5 years in 155 patients showed the best regression of neck circumference (2.2 to 2.6 cm.) and of the area of the scintigram (28 to 31%). 50% of the patients had had recurrences from previous goitre removals and 1 to 3% developed post-therapeutic hypothyroidism. There was no significant change in the level of the peripheral thyroid hormones following treatment, but 10 to 20% were within the hypothyroid range for the area of iodine deficiency."} {"id": "PMID:154446", "title": "[Computer tomographic differential diagnosis of thyroid diseases with special reference to scintigraphic cold spots (author's transl)].", "content": "A high proportion of carcinomas of the thyroid produce scintigraphic cold spots, this finding therefore requires further investigation in order to prevent unnecessary thyroidectomies. In order to clarify the value of computer tomography in thyroid disease, 70 patients with scintigraphic cold spots, or equivocal thyroid scans, were submitted to computer tomography of the neck. The findings in the majority of these cases have been correlated with histological results.", "contents": "[Computer tomographic differential diagnosis of thyroid diseases with special reference to scintigraphic cold spots (author's transl)]. A high proportion of carcinomas of the thyroid produce scintigraphic cold spots, this finding therefore requires further investigation in order to prevent unnecessary thyroidectomies. In order to clarify the value of computer tomography in thyroid disease, 70 patients with scintigraphic cold spots, or equivocal thyroid scans, were submitted to computer tomography of the neck. The findings in the majority of these cases have been correlated with histological results."} {"id": "PMID:154447", "title": "[The diagnosis of liver metastases. A comparison of sonography, scintigraphy and biochemical findings (author's transl)].", "content": "The value of biochemical methods, scintigraphy and sonography in the diagnosis of liver metastases was compared in 150 patients. Of the laboratory methods, gamma-GT proved the most suitable screening method. A negative scan was of considerable value in excluding liver metastases. Positive findings are not always definite and require confirmation. Ultrasound, because of its high accuracy, is the most valuable method for excluding or demonstrating liver metastases. Suggestions for diagnostic procedures are made as a result of these findings.", "contents": "[The diagnosis of liver metastases. A comparison of sonography, scintigraphy and biochemical findings (author's transl)]. The value of biochemical methods, scintigraphy and sonography in the diagnosis of liver metastases was compared in 150 patients. Of the laboratory methods, gamma-GT proved the most suitable screening method. A negative scan was of considerable value in excluding liver metastases. Positive findings are not always definite and require confirmation. Ultrasound, because of its high accuracy, is the most valuable method for excluding or demonstrating liver metastases. Suggestions for diagnostic procedures are made as a result of these findings."} {"id": "PMID:154448", "title": "[Computer tomographic densitometry of human blood. The effect of absorption by parenchymatous organs and effusions (author's transl)].", "content": "In vitro measurements of human blood with varying haemoglobin and plasma concentrations have shown a linear relationship between haemoglobin concentrations and attenuation values. A change of haemoglobin content of 1 g/100 ml. blood produced and equivalent density change of 1.5 HU. Attenuation of normal blood is between 55 to 75 HU, that of plasma about 33 HU. Transudates with a protein concentration of less than 5 g/100 ml. show an attenuation value of less than 26 HU. It is therefore possible to indicate the presence of effusions by computer tomography. The effect of the composition of the blood on the attenuation produced by parenchymatous organs is discussed. It is concluded that attenuation values of organs is not seriously affected by even severe haematological changes.", "contents": "[Computer tomographic densitometry of human blood. The effect of absorption by parenchymatous organs and effusions (author's transl)]. In vitro measurements of human blood with varying haemoglobin and plasma concentrations have shown a linear relationship between haemoglobin concentrations and attenuation values. A change of haemoglobin content of 1 g/100 ml. blood produced and equivalent density change of 1.5 HU. Attenuation of normal blood is between 55 to 75 HU, that of plasma about 33 HU. Transudates with a protein concentration of less than 5 g/100 ml. show an attenuation value of less than 26 HU. It is therefore possible to indicate the presence of effusions by computer tomography. The effect of the composition of the blood on the attenuation produced by parenchymatous organs is discussed. It is concluded that attenuation values of organs is not seriously affected by even severe haematological changes."} {"id": "PMID:154449", "title": "[Chronic occlusion of a renal artery with aneurysms in the para-aortic collateral circulation and multiple aneurysms in both kidneys (author's transl)].", "content": "Chronic occlusion of the main renal artery may be followed by the development of a collateral circulation through ureteric and para-aortic arteries, and through lumbar and suprarenal arteries. A patient with occlusion of the left main renal artery is described, who developed a collateral circulation between the common iliac artery and the distal portion of the renal artery. The para-aortic collateral vessel developed one large and several small aneurysms, and there were aneurysms in both kidneys.", "contents": "[Chronic occlusion of a renal artery with aneurysms in the para-aortic collateral circulation and multiple aneurysms in both kidneys (author's transl)]. Chronic occlusion of the main renal artery may be followed by the development of a collateral circulation through ureteric and para-aortic arteries, and through lumbar and suprarenal arteries. A patient with occlusion of the left main renal artery is described, who developed a collateral circulation between the common iliac artery and the distal portion of the renal artery. The para-aortic collateral vessel developed one large and several small aneurysms, and there were aneurysms in both kidneys."} {"id": "PMID:154450", "title": "[Vascular embolisation in uncontrolled haemorrhages of the bladder caused by tumours and radiation (author's transl)].", "content": "Unilateral or bilateral embolisation of the internal iliac artery was effected in nine patients with incontrollable bleeding due to bladder tumour or invasion of a tumour into the bladder, or as a result of massive alterations of the urinary bladder caused by radiation exposure. A clearly superior haemostasis was achieved via bilateral embolisation (in 4 out of 5 patients) compared with unilateral embolisation (2 of 4 patients). Side effects were observed in two-thirds of the cases (elevated temperature, transient pareses and pain in the gluteal and leg regions).", "contents": "[Vascular embolisation in uncontrolled haemorrhages of the bladder caused by tumours and radiation (author's transl)]. Unilateral or bilateral embolisation of the internal iliac artery was effected in nine patients with incontrollable bleeding due to bladder tumour or invasion of a tumour into the bladder, or as a result of massive alterations of the urinary bladder caused by radiation exposure. A clearly superior haemostasis was achieved via bilateral embolisation (in 4 out of 5 patients) compared with unilateral embolisation (2 of 4 patients). Side effects were observed in two-thirds of the cases (elevated temperature, transient pareses and pain in the gluteal and leg regions)."} {"id": "PMID:154451", "title": "[Evaluation of hepatic and renal function after visceral angiography (author's transl)].", "content": "A prospective study was carried out in 25 patients following visceral angiography using, on average, 3.5 (2.3 to 4.3) ml/kg. of sodium methyl glucamine diatrizoate 76%. No significant changes were found in the liver enzymes (SGTP, LDH and alkaline phosphatase). On the other hand, there was a significant but temporary rise of serum creatinine from 0.9 +/- 0.2 mg% to 1.2 +/- 0.3 mg% as well as transient proteinuria (7 cases) and microhaematuria (6 cases). With the usual contrast doses for visceral angiography, the kidney appears to be the critical organ. In order to reduce the risks of renal complications, contrast doses should be kept to below 4 ml/kg. if possible; angiography should be carried out only if the patient is well hydrated and the indications for angiography should be particularly stringent if there is previous renal damage.", "contents": "[Evaluation of hepatic and renal function after visceral angiography (author's transl)]. A prospective study was carried out in 25 patients following visceral angiography using, on average, 3.5 (2.3 to 4.3) ml/kg. of sodium methyl glucamine diatrizoate 76%. No significant changes were found in the liver enzymes (SGTP, LDH and alkaline phosphatase). On the other hand, there was a significant but temporary rise of serum creatinine from 0.9 +/- 0.2 mg% to 1.2 +/- 0.3 mg% as well as transient proteinuria (7 cases) and microhaematuria (6 cases). With the usual contrast doses for visceral angiography, the kidney appears to be the critical organ. In order to reduce the risks of renal complications, contrast doses should be kept to below 4 ml/kg. if possible; angiography should be carried out only if the patient is well hydrated and the indications for angiography should be particularly stringent if there is previous renal damage."} {"id": "PMID:154452", "title": "[Investigations on pain reduction during peripheral angiography (author's transl)].", "content": "An attempt was made to reduce pain during femoral angiography by adding 1 mg. of Lidocaine/ml. contrast medium in the course of 95 examinations. In a further 87 patients, Diazepam was injected intravenously before the injection of the contrast-Lidocaine mixture. Pain and the feeling of heat was compared with a control group who received contrast medium with 10% physiological saline. There was a highly significant reduction in pain sensation as a result of Lidocaine; pain was further reduced by additional Diazepam, which also reduced heat sensation, but resulted in a fall in blood pressure. High risk patients did not suffer any significant complications. Lidocaine is well suited for out patients, but Diazepam requires a longer period of observation. General anaesthesia has been used only if patients insisted on it or if there was known contrast reaction.", "contents": "[Investigations on pain reduction during peripheral angiography (author's transl)]. An attempt was made to reduce pain during femoral angiography by adding 1 mg. of Lidocaine/ml. contrast medium in the course of 95 examinations. In a further 87 patients, Diazepam was injected intravenously before the injection of the contrast-Lidocaine mixture. Pain and the feeling of heat was compared with a control group who received contrast medium with 10% physiological saline. There was a highly significant reduction in pain sensation as a result of Lidocaine; pain was further reduced by additional Diazepam, which also reduced heat sensation, but resulted in a fall in blood pressure. High risk patients did not suffer any significant complications. Lidocaine is well suited for out patients, but Diazepam requires a longer period of observation. General anaesthesia has been used only if patients insisted on it or if there was known contrast reaction."} {"id": "PMID:154453", "title": "Lumbar erosive intervertebral osteochondrosis. Anatomico-radiological study of a case.", "content": "A radiological and anatomical case study of intervertebral osteochondrosis is presented. X-rays reveal its evolution from an isolated Schmorl's node to a more diffuse lumbar intervertebral osteochondrosis. Macroscopical and microscopical post-mortem examination shows various degrees of disc deterioration with cartilaginous plate flaw and localized or diffuse intravertebral disc herniation. A discussion on the origin of this cartilaginous plate weakness and on the respective significance of the X-ray and biopsy in the differential diagnosis between intervertebral osteochondrosis and infectious spondylitis follows.", "contents": "Lumbar erosive intervertebral osteochondrosis. Anatomico-radiological study of a case. A radiological and anatomical case study of intervertebral osteochondrosis is presented. X-rays reveal its evolution from an isolated Schmorl's node to a more diffuse lumbar intervertebral osteochondrosis. Macroscopical and microscopical post-mortem examination shows various degrees of disc deterioration with cartilaginous plate flaw and localized or diffuse intravertebral disc herniation. A discussion on the origin of this cartilaginous plate weakness and on the respective significance of the X-ray and biopsy in the differential diagnosis between intervertebral osteochondrosis and infectious spondylitis follows."} {"id": "PMID:154454", "title": "[Apophyseolysis, evulsion fractures and osteochondropathy of the anterior inferior iliac spine (author's transl)].", "content": "Evulsion fractures of the anterior inferior iliac spine in adults usually are the result of sudden contraction of the rectus femoris muscle during sporting activities, particularly football. In children, before fusion of the apophysis, there may be an apophyseolysis. This may result in a chondropathy because of abnormal development of the frequently multiple ossification centres. In contrast to the relatively frequent evulsion fractures of the anterior superior iliac spine, such an event is very rare in the anterior inferior iliac spine. Three illustrative cases are described showing the typical combination of history, localisation, pain recurrence during exercise and x-ray changes, which usually consist of a curved osseous structure separate from the iliac bone. These findings permit a correct diagnosis.", "contents": "[Apophyseolysis, evulsion fractures and osteochondropathy of the anterior inferior iliac spine (author's transl)]. Evulsion fractures of the anterior inferior iliac spine in adults usually are the result of sudden contraction of the rectus femoris muscle during sporting activities, particularly football. In children, before fusion of the apophysis, there may be an apophyseolysis. This may result in a chondropathy because of abnormal development of the frequently multiple ossification centres. In contrast to the relatively frequent evulsion fractures of the anterior superior iliac spine, such an event is very rare in the anterior inferior iliac spine. Three illustrative cases are described showing the typical combination of history, localisation, pain recurrence during exercise and x-ray changes, which usually consist of a curved osseous structure separate from the iliac bone. These findings permit a correct diagnosis."} {"id": "PMID:154455", "title": "[Smith-McCort syndrome (author's transl)].", "content": "An 13-year-old mentally normal boy with short-trunked dwarfism is discribed as a case of the Smith-McCort syndrome (SMC-syndrome). His disease has been observed radiologically, clinically an histologically for many years. According to Spranger (23) this disorder differs from the Dyggve-Melchior-Clausen disease (DMC-syndrome) by lacking oligophrenia. Beside a characteristic flattening of the vertebral bodies both syndromes show a lacelike appearance of the iliac crest (crest sign) as a significant radiological sign. Both syndromes appear to be inherited as an autosomal recessive trait.", "contents": "[Smith-McCort syndrome (author's transl)]. An 13-year-old mentally normal boy with short-trunked dwarfism is discribed as a case of the Smith-McCort syndrome (SMC-syndrome). His disease has been observed radiologically, clinically an histologically for many years. According to Spranger (23) this disorder differs from the Dyggve-Melchior-Clausen disease (DMC-syndrome) by lacking oligophrenia. Beside a characteristic flattening of the vertebral bodies both syndromes show a lacelike appearance of the iliac crest (crest sign) as a significant radiological sign. Both syndromes appear to be inherited as an autosomal recessive trait."} {"id": "PMID:154456", "title": "Spondylo-metaphyseal dysplasia (report of a case of common type and three cases of \"new varities\").", "content": "One sporadic case of the common type of spondylo-metaphyseal dysplasia and three cases of \"new varieties\" are reported. In the author's opinion spondylo-metaphyseal dysplasias are much more common than generally recognised. Brachyolmie represents spondylo-metaphyseal dysplasia with mild-minimal metaphyseal changes.", "contents": "Spondylo-metaphyseal dysplasia (report of a case of common type and three cases of \"new varities\"). One sporadic case of the common type of spondylo-metaphyseal dysplasia and three cases of \"new varieties\" are reported. In the author's opinion spondylo-metaphyseal dysplasias are much more common than generally recognised. Brachyolmie represents spondylo-metaphyseal dysplasia with mild-minimal metaphyseal changes."} {"id": "PMID:154457", "title": "[Algorithms in the radiological diagnosis of malignant disease (author's transl)].", "content": "Algorithms in the diagnosis of malignant disease have the aim to produce a diagnosis as quickly, as certainly and as simply as possible. The first phase consists of general non-invasive methods which should be as simple as possible. If the results are positive this should be followed immediately by percutaneous biopsy in order to produce cytological confirmation of the diagnosis as quickly as possible. If the original investigations were negative, those special methods of investigation should be used which are most likely to make a diagnosis. This is followed by investigations which throw light on the most appropriate form of treatment. This scheme has been illustrated by special algorithms for carcinoma of the bronchus, the pancreas and the breast.", "contents": "[Algorithms in the radiological diagnosis of malignant disease (author's transl)]. Algorithms in the diagnosis of malignant disease have the aim to produce a diagnosis as quickly, as certainly and as simply as possible. The first phase consists of general non-invasive methods which should be as simple as possible. If the results are positive this should be followed immediately by percutaneous biopsy in order to produce cytological confirmation of the diagnosis as quickly as possible. If the original investigations were negative, those special methods of investigation should be used which are most likely to make a diagnosis. This is followed by investigations which throw light on the most appropriate form of treatment. This scheme has been illustrated by special algorithms for carcinoma of the bronchus, the pancreas and the breast."} {"id": "PMID:154458", "title": "[Success and apparent success resulting from early cancer diagnosis (author's transl)].", "content": "Cancer screening techniques are of great value in improving the results of treatment of various tumours. Unfortunately screening and early diagnosis of cancers does not improve the prognosis in every case. Early diagnosis may lead to an apparent success without affecting the final outcome of treatment. Early diagnosis may even be harmful to the patient if the diagnostic and therapeutic methods lead to dissemination of the tumour, as has been shown by a number of authors. Consequently cancer screening and early diagnosis should be confined to those selected tumours which are not affected adversely by diagnostic methods.", "contents": "[Success and apparent success resulting from early cancer diagnosis (author's transl)]. Cancer screening techniques are of great value in improving the results of treatment of various tumours. Unfortunately screening and early diagnosis of cancers does not improve the prognosis in every case. Early diagnosis may lead to an apparent success without affecting the final outcome of treatment. Early diagnosis may even be harmful to the patient if the diagnostic and therapeutic methods lead to dissemination of the tumour, as has been shown by a number of authors. Consequently cancer screening and early diagnosis should be confined to those selected tumours which are not affected adversely by diagnostic methods."} {"id": "PMID:154466", "title": "[Ten years experience with laparoscopy in the state women's clinic of Nurenberg].", "content": "During the period from 1968--1977 2400 laparoscopies were performed. Of these 10.7% were for diagnostic purposes only, in 3.6% of the cases laparoscopy was combined with biopsie and in 85.7% with tubal sterilization. Deaths or serious bleedings did not occur, laparotomies were not necessary. Total insignificant complications amounted to 1.6% (1.3% small bleedings which did not necessitate an operation and in 0.3% clinical signs of peritonitis, these disappeared after 3 to 15 days). In 0.7% laparoscopy was interrupted because of poor vision. Nine of 2055 women became pregnant after sterilization (4.5 pregnancies/1000 sterilizations). In 2 cases the ligamentum rotundum was coagulated, in 7 cases recanalization was histologically confirmed. Until Oct. 1975 coagulation was unipolar, afterwords bipolar. In 45.3% the patients had undergone an operation before, like Ceasarian section, gallbladder operation, appendectomy or umbilical hernia operation. Patients with longitudinal incision, with preceding peritonitis or ileus were excluded from laparoscopy. Laparoscopy was performed by all assistents during their last year of clinical instruction. Their first 30 laparoscopies were done under control, every assistent performed about 100 laparoscopies.", "contents": "[Ten years experience with laparoscopy in the state women's clinic of Nurenberg]. During the period from 1968--1977 2400 laparoscopies were performed. Of these 10.7% were for diagnostic purposes only, in 3.6% of the cases laparoscopy was combined with biopsie and in 85.7% with tubal sterilization. Deaths or serious bleedings did not occur, laparotomies were not necessary. Total insignificant complications amounted to 1.6% (1.3% small bleedings which did not necessitate an operation and in 0.3% clinical signs of peritonitis, these disappeared after 3 to 15 days). In 0.7% laparoscopy was interrupted because of poor vision. Nine of 2055 women became pregnant after sterilization (4.5 pregnancies/1000 sterilizations). In 2 cases the ligamentum rotundum was coagulated, in 7 cases recanalization was histologically confirmed. Until Oct. 1975 coagulation was unipolar, afterwords bipolar. In 45.3% the patients had undergone an operation before, like Ceasarian section, gallbladder operation, appendectomy or umbilical hernia operation. Patients with longitudinal incision, with preceding peritonitis or ileus were excluded from laparoscopy. Laparoscopy was performed by all assistents during their last year of clinical instruction. Their first 30 laparoscopies were done under control, every assistent performed about 100 laparoscopies."} {"id": "PMID:154467", "title": "[Procedure for the acknowledgement of occupational skin diseases].", "content": "Following the amendment to the Occupational Diseases Order (Berufskrankheitenverordnung) with effect as of Jan. 1, 1977, the number of occupational skin diseases acknowledged is expected to increase. Knowledge of the pre-requisites in terms of insurance law regarding the acknowledgement of an occupational disease subject to payment of compensation places early detection and preventive measures in another light. The acknowledgement procedure and dermatological early-diagnosis procedure are explained in detail.", "contents": "[Procedure for the acknowledgement of occupational skin diseases]. Following the amendment to the Occupational Diseases Order (Berufskrankheitenverordnung) with effect as of Jan. 1, 1977, the number of occupational skin diseases acknowledged is expected to increase. Knowledge of the pre-requisites in terms of insurance law regarding the acknowledgement of an occupational disease subject to payment of compensation places early detection and preventive measures in another light. The acknowledgement procedure and dermatological early-diagnosis procedure are explained in detail."} {"id": "PMID:154468", "title": "The decay of memory of cell-mediated cytotoxicity after primary sensitization in vivo against a tumor allograft.", "content": "The length of time mice were able to show a secondary cell-mediated response after a tumor allograft was investigated. C57B1/6 mice were inoculated ip with P-815 mastocytoma cells and, at selected time intervals up to 12 months after immunization, spleen cells were placed in JLC in an attempt to generate secondary CTL activity. It was found, as measured by the 51Cr-release assay, that all mice tested had significant secondary CTL activity 3 months after allograft. The ability to generate a secondary response then decreased with considerable individual variation up to 6 months post-immunization. No significant difference in CTL activity was found between immunized and age-matched control mice 12 months after tumor allograft.", "contents": "The decay of memory of cell-mediated cytotoxicity after primary sensitization in vivo against a tumor allograft. The length of time mice were able to show a secondary cell-mediated response after a tumor allograft was investigated. C57B1/6 mice were inoculated ip with P-815 mastocytoma cells and, at selected time intervals up to 12 months after immunization, spleen cells were placed in JLC in an attempt to generate secondary CTL activity. It was found, as measured by the 51Cr-release assay, that all mice tested had significant secondary CTL activity 3 months after allograft. The ability to generate a secondary response then decreased with considerable individual variation up to 6 months post-immunization. No significant difference in CTL activity was found between immunized and age-matched control mice 12 months after tumor allograft."} {"id": "PMID:154469", "title": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. X. The organ sources of the stimulator and responder cells in the mixed leukocyte culture reaction.", "content": "This investigation is concerned with the elucidation of the organ distribution of stimulator and responder cells in the one-way MLR (mixed leukocyte reaction). The organs investigated were the thymus, bone marrow, spleen, lymph nodes, appendix, sacculus rotundus, Peyer's patches and the circulation. Mitomycin-C treated bone marrow cells and WBC were used as stimulator cells to investigate, in a systematic fashion, the blastogenic responses of the responder cells of the allogeneic lymphoid organs. Responses occurred optimally on day 5 of culture and were dependent upon responder cell concentration. Peyer's patches and mesenteric lymph node cells responded to a greater extent than the cell of any of the other lymphoid organs. Rabbit WBC responded consistently in the one-way MLR, in contrast to the findings of other investigators. Cells of the thymus and bone marrow cultured individually or in combination did not respond. The cells of the different lymphoid organs were investigated as to their stimulator cell activity. Responder WBC or spleen cells were cultured with the mitomycin-C treated stimulator cells. On a per cell basis, the cells of the Peyer's patches, spleen and mesenteric lymph nodes were the most potent stimulator cells. There was no correlation between stimulating capacity and the percentage of stimulator cells bearing surface immunoglobulins. Thus, the stimulating capacity of these cells in the one-way MLR is not a reflection of, or dependent upon, surface immunoglobulins. A consistent finding was an MLR-like response of spleen cells and WBC cultured with autologous mitomycin-C treated Peyer's patches, sacculus rotundus or appendix cells.", "contents": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. X. The organ sources of the stimulator and responder cells in the mixed leukocyte culture reaction. This investigation is concerned with the elucidation of the organ distribution of stimulator and responder cells in the one-way MLR (mixed leukocyte reaction). The organs investigated were the thymus, bone marrow, spleen, lymph nodes, appendix, sacculus rotundus, Peyer's patches and the circulation. Mitomycin-C treated bone marrow cells and WBC were used as stimulator cells to investigate, in a systematic fashion, the blastogenic responses of the responder cells of the allogeneic lymphoid organs. Responses occurred optimally on day 5 of culture and were dependent upon responder cell concentration. Peyer's patches and mesenteric lymph node cells responded to a greater extent than the cell of any of the other lymphoid organs. Rabbit WBC responded consistently in the one-way MLR, in contrast to the findings of other investigators. Cells of the thymus and bone marrow cultured individually or in combination did not respond. The cells of the different lymphoid organs were investigated as to their stimulator cell activity. Responder WBC or spleen cells were cultured with the mitomycin-C treated stimulator cells. On a per cell basis, the cells of the Peyer's patches, spleen and mesenteric lymph nodes were the most potent stimulator cells. There was no correlation between stimulating capacity and the percentage of stimulator cells bearing surface immunoglobulins. Thus, the stimulating capacity of these cells in the one-way MLR is not a reflection of, or dependent upon, surface immunoglobulins. A consistent finding was an MLR-like response of spleen cells and WBC cultured with autologous mitomycin-C treated Peyer's patches, sacculus rotundus or appendix cells."} {"id": "PMID:154470", "title": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. XI. The accelerated response in the one-way MLR of rabbit WBC from skin allograft recipients.", "content": "The relationship between allograft rejection and the response in the one-way mixed leucocyte reaction (MLR) of the WBC of allograft recipients was investigated. The responses of the WBC were assessed prior to skin allografting and subsequent to rejection of the allograft. The optimal MLR response of the WBC from the allografted rabbit stimulated with cells from the allograft donor occurred on days 3 to 4 of culture and by day 6 the MLR response was down to control levels. This accelerated response by the allograft-sensitized cells was specific to stimulator cells from the allograft donor as stimulator cells from a third party rabbit induced a normal MLR response by these cells, that is, an optimal response on days 5 to 7 of culture. No evidence of cytotoxic cells was obtained in cultures of cells from allograft-sensitized rabbits. The implications of these results are discussed.", "contents": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. XI. The accelerated response in the one-way MLR of rabbit WBC from skin allograft recipients. The relationship between allograft rejection and the response in the one-way mixed leucocyte reaction (MLR) of the WBC of allograft recipients was investigated. The responses of the WBC were assessed prior to skin allografting and subsequent to rejection of the allograft. The optimal MLR response of the WBC from the allografted rabbit stimulated with cells from the allograft donor occurred on days 3 to 4 of culture and by day 6 the MLR response was down to control levels. This accelerated response by the allograft-sensitized cells was specific to stimulator cells from the allograft donor as stimulator cells from a third party rabbit induced a normal MLR response by these cells, that is, an optimal response on days 5 to 7 of culture. No evidence of cytotoxic cells was obtained in cultures of cells from allograft-sensitized rabbits. The implications of these results are discussed."} {"id": "PMID:154471", "title": "Role of granulocytes in immune complex-induced tissue injuries.", "content": "Tissue injury of many types may be caused by deposited complexes of antigen and antibody. The circumstances under which the complexes form and deposit often determine the location and type of injury observed: If the complex forms in the circulation, deposition may occur in arterial walls and glomeruli, initiating lesions in those tissues. If the complex forms in the synovial tissues or spaces, then the reaction will develop at that point. Any local source of antigen will initiate these lesions once antibody is formed. If the source of antigen persists, antibody-forming cells soon establish themselves locally as they do in the active Arthus reaction, and injury will become chronic. When the antibody formed is capable of activating complement, polymorphonuclear leukocytes (PMNs, neutrophils) will accumulate, leading to release of injurious constituents. Such is the case in acute glomerulonephritis, arteritis, synovitis, and vasculitis. The ability of complement to attract the PMNs has been demonstrated as an in vitro phenomenon and as a clear possibility in vivo. The requirement of PMNs in the development of the lesions has been demonstrated. The process by which PMNs and other cells (platelets, mast cells, basophils, and macrophages) release injurious constituents is of great interest currently. The exocytosis of their cytoplasmic granules constitutes the major mechanism of release and involves a complicated series of events outlined in this review. The constituents of PMNs capable of injuring tissue in various ways is described, from peptides capable of increasing vascular permeability, to enzymes that indirectly bring more PMNs and other cells into the lesion, to proteolytic enzymes that hydrolyze vital structures in the tissues. These agents were most likely designed to rid the host of invaders; but at times they are unfortunately directed against the host's own tissues.", "contents": "Role of granulocytes in immune complex-induced tissue injuries. Tissue injury of many types may be caused by deposited complexes of antigen and antibody. The circumstances under which the complexes form and deposit often determine the location and type of injury observed: If the complex forms in the circulation, deposition may occur in arterial walls and glomeruli, initiating lesions in those tissues. If the complex forms in the synovial tissues or spaces, then the reaction will develop at that point. Any local source of antigen will initiate these lesions once antibody is formed. If the source of antigen persists, antibody-forming cells soon establish themselves locally as they do in the active Arthus reaction, and injury will become chronic. When the antibody formed is capable of activating complement, polymorphonuclear leukocytes (PMNs, neutrophils) will accumulate, leading to release of injurious constituents. Such is the case in acute glomerulonephritis, arteritis, synovitis, and vasculitis. The ability of complement to attract the PMNs has been demonstrated as an in vitro phenomenon and as a clear possibility in vivo. The requirement of PMNs in the development of the lesions has been demonstrated. The process by which PMNs and other cells (platelets, mast cells, basophils, and macrophages) release injurious constituents is of great interest currently. The exocytosis of their cytoplasmic granules constitutes the major mechanism of release and involves a complicated series of events outlined in this review. The constituents of PMNs capable of injuring tissue in various ways is described, from peptides capable of increasing vascular permeability, to enzymes that indirectly bring more PMNs and other cells into the lesion, to proteolytic enzymes that hydrolyze vital structures in the tissues. These agents were most likely designed to rid the host of invaders; but at times they are unfortunately directed against the host's own tissues."} {"id": "PMID:154472", "title": "Stability of the resident microflora and the bacteriocinogeny of Streptococcus mutans as factors affecting its establishment in specific pathogen-free rats.", "content": "The outcome of the experimental implantation of Streptococcus mutans strains in humans and animals is unpredictable, and neither success nor failure can be explained. It seems logical to assume that, apart from dietary and host factors, the characteristics of the S. mutans strain involved and those of the resident plaque microflora are important in colonization. For example, previous work in this laboratory suggested that bacteriocin production accounts at least in part for the establishment of an invading bacterium in a microbial ecosystem. In the present study, a complex specific pathogen-free Ny plaque ecosystem was obtained by the inoculation of specific pathogen-free rats with Actinomyces viscosus Ny1 and S. sanguis Ny101, and the establishment of S. mutans in such rats was then examined. It was found that bacteriocinogenic (bac(+)) strains generally colonized in much higher proportions than non-bacteriocinogenic (bac(-)) strains. Moreover, the longer the delay in introducing S. mutans, the poorer was its establishment. Shortly after inoculation of strains Ny1 and Ny101, there is probably a transient state in which microbial equilibrium has not been reached, but later the specific pathogen-free Ny system attains a stable climax community which more strongly resists invaders. The ability of a number of S. mutans strains to establish in such a climax community was then examined, and it was found that bac(+) strains generally established at a higher level than did bac(-) strains. In summary, it was concluded that, although the bac(+) state is an important property in the successful invasion of a plaque by S. mutans, the stability of the resident microflora is also an important factor.", "contents": "Stability of the resident microflora and the bacteriocinogeny of Streptococcus mutans as factors affecting its establishment in specific pathogen-free rats. The outcome of the experimental implantation of Streptococcus mutans strains in humans and animals is unpredictable, and neither success nor failure can be explained. It seems logical to assume that, apart from dietary and host factors, the characteristics of the S. mutans strain involved and those of the resident plaque microflora are important in colonization. For example, previous work in this laboratory suggested that bacteriocin production accounts at least in part for the establishment of an invading bacterium in a microbial ecosystem. In the present study, a complex specific pathogen-free Ny plaque ecosystem was obtained by the inoculation of specific pathogen-free rats with Actinomyces viscosus Ny1 and S. sanguis Ny101, and the establishment of S. mutans in such rats was then examined. It was found that bacteriocinogenic (bac(+)) strains generally colonized in much higher proportions than non-bacteriocinogenic (bac(-)) strains. Moreover, the longer the delay in introducing S. mutans, the poorer was its establishment. Shortly after inoculation of strains Ny1 and Ny101, there is probably a transient state in which microbial equilibrium has not been reached, but later the specific pathogen-free Ny system attains a stable climax community which more strongly resists invaders. The ability of a number of S. mutans strains to establish in such a climax community was then examined, and it was found that bac(+) strains generally established at a higher level than did bac(-) strains. In summary, it was concluded that, although the bac(+) state is an important property in the successful invasion of a plaque by S. mutans, the stability of the resident microflora is also an important factor."} {"id": "PMID:154473", "title": "Restoration of T-cell responsiveness by thymosin: expression of anti-tuberculous immunity in mouse lungs.", "content": "Specific pathogen-free, adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) B6D2 mice were infected aerogenically with 1 X 10(3) to 5 X 10(3) live BCG Pasteur. Seven days later a group of the mice was placed on a 14-day regimen of 20 mg of calf thymosin per kg per day, and the growth of the BCG in the lungs, spleen, inguinal lymph node, bone marrow, and blood was determined for up to 90 days. The thymosin treatment was followed by a decline in the BCG counts for the lungs and spleens of the THXB mice, whereas the saline-treated controls showed no such decline with time. The thymosin-treated mice did not develop progressive BCG infections in the test lymph nodes or in the bone marrow, both of which became positive in the THXB mice. Spleen cells were harvested from thymosin-treated THXB donors, filtered through nylon wool, and infused three times into BCG-infected THXB recipients. The lung BCG counts declined approximately 10-fold by day 90 compared with THXB mice which received THXB spleen cells. The transferred immune response was only slightly smaller numerically than that seen in THXB mice infused with BCG-immune lymphocytes from normal donors.", "contents": "Restoration of T-cell responsiveness by thymosin: expression of anti-tuberculous immunity in mouse lungs. Specific pathogen-free, adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) B6D2 mice were infected aerogenically with 1 X 10(3) to 5 X 10(3) live BCG Pasteur. Seven days later a group of the mice was placed on a 14-day regimen of 20 mg of calf thymosin per kg per day, and the growth of the BCG in the lungs, spleen, inguinal lymph node, bone marrow, and blood was determined for up to 90 days. The thymosin treatment was followed by a decline in the BCG counts for the lungs and spleens of the THXB mice, whereas the saline-treated controls showed no such decline with time. The thymosin-treated mice did not develop progressive BCG infections in the test lymph nodes or in the bone marrow, both of which became positive in the THXB mice. Spleen cells were harvested from thymosin-treated THXB donors, filtered through nylon wool, and infused three times into BCG-infected THXB recipients. The lung BCG counts declined approximately 10-fold by day 90 compared with THXB mice which received THXB spleen cells. The transferred immune response was only slightly smaller numerically than that seen in THXB mice infused with BCG-immune lymphocytes from normal donors."} {"id": "PMID:154474", "title": "Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model.", "content": "Viable bacteria were not cultured from the mesenteric lymph nodes, spleens, or livers of specific-pathogen-free (SPF) mice. Viable enteric bacteria, primarily indigenous Escherichia coli and lactobacilli, were present in the mesenteric lymph nodes of gnotobiotic mice inoculated intragastrically with the whole cecal microflora from SPF mice but not in the nodes of control SPF mice similarly inoculated. These indigenous E. coli also were cultured from the mesenteric lymph nodes of 96% of gnotobiotic mice monoassociated with E. coli but from none of the mesenteric lymph nodes of SPF mice inoculated with the E. coli. Furthermore, viable E. coli were detected in the mesenteric lymph nodes of these monoassociated gnotobiotes for as long as 112 days after inoculation. Indigenous Lactobacillus acidophilus also translocated to the mesenteric lymph nodes of gnotobiotic mice monoassociated with L. acidophilus. Apparently, there are mechanisms active in SPF mice inhibiting translocation of indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes, spleens, and livers, whereas these mechanisms are either absent or reduced in gnotobiotic mice. Indigenous E. coli maintained higher population levels in the gastrointestinal tracts of the gnotobiotes compared with their population levels in SPF mice, suggesting that high bacterial population levels might promote translocation of certain bacteria from the gastrointestinal lumen to the mesenteric lymph nodes. Gnotobiotic and SPF mice, therefore, provide experimental models for determining the nature of the mechanisms operating to confine indigenous bacteria to the gastrointestinal tract in normal, healthy animals.", "contents": "Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Viable bacteria were not cultured from the mesenteric lymph nodes, spleens, or livers of specific-pathogen-free (SPF) mice. Viable enteric bacteria, primarily indigenous Escherichia coli and lactobacilli, were present in the mesenteric lymph nodes of gnotobiotic mice inoculated intragastrically with the whole cecal microflora from SPF mice but not in the nodes of control SPF mice similarly inoculated. These indigenous E. coli also were cultured from the mesenteric lymph nodes of 96% of gnotobiotic mice monoassociated with E. coli but from none of the mesenteric lymph nodes of SPF mice inoculated with the E. coli. Furthermore, viable E. coli were detected in the mesenteric lymph nodes of these monoassociated gnotobiotes for as long as 112 days after inoculation. Indigenous Lactobacillus acidophilus also translocated to the mesenteric lymph nodes of gnotobiotic mice monoassociated with L. acidophilus. Apparently, there are mechanisms active in SPF mice inhibiting translocation of indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes, spleens, and livers, whereas these mechanisms are either absent or reduced in gnotobiotic mice. Indigenous E. coli maintained higher population levels in the gastrointestinal tracts of the gnotobiotes compared with their population levels in SPF mice, suggesting that high bacterial population levels might promote translocation of certain bacteria from the gastrointestinal lumen to the mesenteric lymph nodes. Gnotobiotic and SPF mice, therefore, provide experimental models for determining the nature of the mechanisms operating to confine indigenous bacteria to the gastrointestinal tract in normal, healthy animals."} {"id": "PMID:154475", "title": "Staphylococcus aureus cell surface: capsule as a barrier to bacteriophage adsorption.", "content": "Encapsulated Staphylococcus aureus strains M and Smith diffuse bound phage 84 and 52A much less efficiently than their unencapsulated counterparts, M variant and Smith compact. It is proposed that the capsule acts as a barrier excluding phage from interaction with their receptor (cell wall peptidoglycan and teichoic acid). Inefficient phage adsorption by encapsulated staphylococci may explain, in part, the poor phage typing of such strains.", "contents": "Staphylococcus aureus cell surface: capsule as a barrier to bacteriophage adsorption. Encapsulated Staphylococcus aureus strains M and Smith diffuse bound phage 84 and 52A much less efficiently than their unencapsulated counterparts, M variant and Smith compact. It is proposed that the capsule acts as a barrier excluding phage from interaction with their receptor (cell wall peptidoglycan and teichoic acid). Inefficient phage adsorption by encapsulated staphylococci may explain, in part, the poor phage typing of such strains."} {"id": "PMID:154476", "title": "Detection of immune complexes on the surface of polymorphonuclear neutrophils.", "content": "A simple immunohistological test has been developed to detect and to quantitate the presence of immune complexes (IC) on the surface of human polymorphonuclear neutrophils (PMN). The interaction between IC and PMN has been evaluated in several human IC diseases. High amounts of immunoglobulins (Ig) and C3 were detected on the PMN surface from these patients. The deposits of Ig and C3 were inversely related to the percentage of membrane-free receptors for Fc and C3.", "contents": "Detection of immune complexes on the surface of polymorphonuclear neutrophils. A simple immunohistological test has been developed to detect and to quantitate the presence of immune complexes (IC) on the surface of human polymorphonuclear neutrophils (PMN). The interaction between IC and PMN has been evaluated in several human IC diseases. High amounts of immunoglobulins (Ig) and C3 were detected on the PMN surface from these patients. The deposits of Ig and C3 were inversely related to the percentage of membrane-free receptors for Fc and C3."} {"id": "PMID:154477", "title": "Circulating immune complexes in acute uveitis: a possible association with the histocompatibility complex locus antigen B27.", "content": "39 patients with acute anterior uveitis were investigated for the presence of circulating immune complex (IC) and correlation with the major histocompatibility complex antigen B27 (HLA-B27). ICs were demonstrated by a number of techniques including rheumatoid factor, complement (C) activation, anticomplementary activity, cryoglobulins, inhibition of IgG-EA rosette formation and neutrophil chemotactic index (NCI) in plasma. ICs were most frequently detected in HLA-B27-negative patients. These results indicate that deposition of circulating ICs may be involved in the pathogenesis of acute anterior uveitis, especially in HLA-B27-negative patients.", "contents": "Circulating immune complexes in acute uveitis: a possible association with the histocompatibility complex locus antigen B27. 39 patients with acute anterior uveitis were investigated for the presence of circulating immune complex (IC) and correlation with the major histocompatibility complex antigen B27 (HLA-B27). ICs were demonstrated by a number of techniques including rheumatoid factor, complement (C) activation, anticomplementary activity, cryoglobulins, inhibition of IgG-EA rosette formation and neutrophil chemotactic index (NCI) in plasma. ICs were most frequently detected in HLA-B27-negative patients. These results indicate that deposition of circulating ICs may be involved in the pathogenesis of acute anterior uveitis, especially in HLA-B27-negative patients."} {"id": "PMID:154478", "title": "Papillon-Lefevre syndrome.", "content": "Two cases of Papillon-Lefevre Syndrome (PLS) in a family are reported. Association of recurrent infections, arachnodactyly, intracranial calcification and phalangeal abnormality have been observed. Because there is no history of consanguinity, and autosomal recessive pattern of inheritance is suggested.", "contents": "Papillon-Lefevre syndrome. Two cases of Papillon-Lefevre Syndrome (PLS) in a family are reported. Association of recurrent infections, arachnodactyly, intracranial calcification and phalangeal abnormality have been observed. Because there is no history of consanguinity, and autosomal recessive pattern of inheritance is suggested."} {"id": "PMID:154480", "title": "Does adipose tissue cellularity or the age of onset of obesity influence the response to short-term inpatient treatment of obese women?", "content": "Thirty-three obese women were admitted as inpatients to a metabolic ward and had an average intake of 3.35 MJ (800 kcal) daily for three weeks. Fat biopsies were taken at three subcutaneous sites and average fat cell mass (CM) and apparent fat cell number (FCN) were calculated. There was no significant correlation between adipose tissue cellularity (CM or FCN) and total weight loss or resting metabolic rate, provided due allowances were made for the severity of obesity in each case. Neither was there any significant correlation between short-term weight loss and the age of onset of obesity. Resting metabolic rate, and not adipose tissue cellularity or age of onset of obesity, is a better indicator of short-term weight loss under controlled inpatient conditions.", "contents": "Does adipose tissue cellularity or the age of onset of obesity influence the response to short-term inpatient treatment of obese women? Thirty-three obese women were admitted as inpatients to a metabolic ward and had an average intake of 3.35 MJ (800 kcal) daily for three weeks. Fat biopsies were taken at three subcutaneous sites and average fat cell mass (CM) and apparent fat cell number (FCN) were calculated. There was no significant correlation between adipose tissue cellularity (CM or FCN) and total weight loss or resting metabolic rate, provided due allowances were made for the severity of obesity in each case. Neither was there any significant correlation between short-term weight loss and the age of onset of obesity. Resting metabolic rate, and not adipose tissue cellularity or age of onset of obesity, is a better indicator of short-term weight loss under controlled inpatient conditions."} {"id": "PMID:154481", "title": "Immunohistochemical identification of slow-tonic fibers in human extrinsic eye muscles.", "content": "A fluorescent antiserum against myosin from chicken anterior latissimus dorsi muscle, which stains specifically the multiply innervated slow fibers of birds and amphibians, was applied to frozen sections of human extraocular muscles. A proportion of fibers in oculorotatory muscles were labeled by the antiserum. In contrast, no labeled extrafusal fiber was present in the levator palpebrae or in other body muscles. Serial study of sections stained for acetylcholinesterase and myosin ATPase showed that the labeled fibers in human oculorotatory muscles are multiply innervated and display acid-stable myosin ATPase activity.", "contents": "Immunohistochemical identification of slow-tonic fibers in human extrinsic eye muscles. A fluorescent antiserum against myosin from chicken anterior latissimus dorsi muscle, which stains specifically the multiply innervated slow fibers of birds and amphibians, was applied to frozen sections of human extraocular muscles. A proportion of fibers in oculorotatory muscles were labeled by the antiserum. In contrast, no labeled extrafusal fiber was present in the levator palpebrae or in other body muscles. Serial study of sections stained for acetylcholinesterase and myosin ATPase showed that the labeled fibers in human oculorotatory muscles are multiply innervated and display acid-stable myosin ATPase activity."} {"id": "PMID:154482", "title": "[Unusual, congenital universal polydysplasia].", "content": "The author reports a 40-year-old patient with clinical manifestations of universal polydysplasia, which cannot be linked to any of the 28 well defined forms of dysplasia including the keratosis syndromes.", "contents": "[Unusual, congenital universal polydysplasia]. The author reports a 40-year-old patient with clinical manifestations of universal polydysplasia, which cannot be linked to any of the 28 well defined forms of dysplasia including the keratosis syndromes."} {"id": "PMID:154483", "title": "[Phototoxic reactions to 8-methoxypsoralen as occupational dermatosis].", "content": "The case history of a 50-year-old assistant pharmacist, who had been working with 8-methoxypsoralene (8-MOP) without any protection, is discussed. Shortly after this work, he was exposed to sunlight. Within 72 h he developed a typical local reaction with painful erythema and vesiculation on the back of both hands, followed by hyperpigmentation a week later. Light testing on skin dusted with 8-MOP resulted in the same clinical picture. Histopathological examination of a lesion showed the characteristics of a phototoxic dermatitis. Guidelines for the prevention of complications in those who are professionally exposed to 8-MOP are emphasized.", "contents": "[Phototoxic reactions to 8-methoxypsoralen as occupational dermatosis]. The case history of a 50-year-old assistant pharmacist, who had been working with 8-methoxypsoralene (8-MOP) without any protection, is discussed. Shortly after this work, he was exposed to sunlight. Within 72 h he developed a typical local reaction with painful erythema and vesiculation on the back of both hands, followed by hyperpigmentation a week later. Light testing on skin dusted with 8-MOP resulted in the same clinical picture. Histopathological examination of a lesion showed the characteristics of a phototoxic dermatitis. Guidelines for the prevention of complications in those who are professionally exposed to 8-MOP are emphasized."} {"id": "PMID:154484", "title": "[Differential diagnostic studies using the dermatoscope in selected diseases].", "content": "The Zeis dermatoscope can be used beyond its known applications for precise and detailed skin surface examinations of different types of dermatosis. Differential diagnostic problems are solved by comparative observation of efflorescence and efflorescence fields of similar appearance. The examination series presented, the results of which are discussed in detail, is concerned mainly with surface examinations of parapsoriasis en plaques, seborrhea en plaques and the clinically similar early forms of mycosis fungoides. Also mentioned are examinations of lichen sclerosus et atrophicus and circumscribed scleroderma, lichen planus, Hutchinson-Dubreuilh freckle and similarly appearing facial verruca seborrhoica, as well as fresh dispersions of foreign bodies. The didactic value is underlined by color photographs taken of diseased skin and nails with the dermatoscope at various magnifications. Finally, a description is given of possible instrument extensions.", "contents": "[Differential diagnostic studies using the dermatoscope in selected diseases]. The Zeis dermatoscope can be used beyond its known applications for precise and detailed skin surface examinations of different types of dermatosis. Differential diagnostic problems are solved by comparative observation of efflorescence and efflorescence fields of similar appearance. The examination series presented, the results of which are discussed in detail, is concerned mainly with surface examinations of parapsoriasis en plaques, seborrhea en plaques and the clinically similar early forms of mycosis fungoides. Also mentioned are examinations of lichen sclerosus et atrophicus and circumscribed scleroderma, lichen planus, Hutchinson-Dubreuilh freckle and similarly appearing facial verruca seborrhoica, as well as fresh dispersions of foreign bodies. The didactic value is underlined by color photographs taken of diseased skin and nails with the dermatoscope at various magnifications. Finally, a description is given of possible instrument extensions."} {"id": "PMID:154485", "title": "[The explained and the unexplained in dermatological immunology].", "content": "By means of classical allergologic and modern immunologic test methods, as well as recent knowledge about antigens and antibody reactions, some dermatoses can be classified with good probability into the allergy types of Coombs and Gell. In other dermatoses much remains unclear. The problems are discussed with regard to several dermatoses and attempts are made to explain some skin alterations by the mentioned immunologic types of reaction.", "contents": "[The explained and the unexplained in dermatological immunology]. By means of classical allergologic and modern immunologic test methods, as well as recent knowledge about antigens and antibody reactions, some dermatoses can be classified with good probability into the allergy types of Coombs and Gell. In other dermatoses much remains unclear. The problems are discussed with regard to several dermatoses and attempts are made to explain some skin alterations by the mentioned immunologic types of reaction."} {"id": "PMID:154486", "title": "[The persistence of chromate allergy in cement eczema].", "content": "93 patients with contact allergy to chromates were followed up for 15 years during which time they were examined clinically and patch tested quantitatively at regular intervals. Results demonstrate that contact allergy to chromates and cement eczema differ from other occupational dermatoses mainly because of their persistence after a change of exposure and occupation. Explanations for this observation are offered.", "contents": "[The persistence of chromate allergy in cement eczema]. 93 patients with contact allergy to chromates were followed up for 15 years during which time they were examined clinically and patch tested quantitatively at regular intervals. Results demonstrate that contact allergy to chromates and cement eczema differ from other occupational dermatoses mainly because of their persistence after a change of exposure and occupation. Explanations for this observation are offered."} {"id": "PMID:154487", "title": "[Hyperosmolar nonketotic diabetic coma in children].", "content": "Nonketotic hyperosmolar diabetic coma is a rare manifestation of juvenile diabetes, in contrast to adult onset diabetes. To date only 20 cases have been published, the majority of them infants and toddlers. This type of diabetic coma is seen with unusual frequency in children with Down's syndrome and psychomotor retardation. The clinical picture is characterised by severe dehydration, hyperglycemia with often extremely high blood sugar levels, hyperosmolarity and glucosuria without ketonuria. Mortality in children has been high (24%). This paper reports the case of a 14-month-old girl with Down's syndrome. Clinical and therapeutic as well as pathogenetic aspects are discussed.", "contents": "[Hyperosmolar nonketotic diabetic coma in children]. Nonketotic hyperosmolar diabetic coma is a rare manifestation of juvenile diabetes, in contrast to adult onset diabetes. To date only 20 cases have been published, the majority of them infants and toddlers. This type of diabetic coma is seen with unusual frequency in children with Down's syndrome and psychomotor retardation. The clinical picture is characterised by severe dehydration, hyperglycemia with often extremely high blood sugar levels, hyperosmolarity and glucosuria without ketonuria. Mortality in children has been high (24%). This paper reports the case of a 14-month-old girl with Down's syndrome. Clinical and therapeutic as well as pathogenetic aspects are discussed."} {"id": "PMID:154492", "title": "Effect of an inhaled atropinelike agent on normal airway function.", "content": "Ten normal subjects inhaled 80 microgram ipratropium or placebo. Body plethysmograph studies showed that ipratropium increased specific conductance (0.14-0.21 s-1.cmH2O-1) and increased flow rates during both maximal and partial forced expiratory maneuvers at all volumes from 50 to 10% vital capacity (P less than 0.01). Ipratropium produced no change in quasi-static or dynamic compliance, closing volume, or the slope of phase III of the closing volume trace, but there was an increase in the height of phase IV (P less than 0.01). Specific conductance reflects central airways caliber, whereas flow rates at low lung volumes in the absence of alteration in static recoil pressure may reflect the caliber of more peripheral airways. We conclude that inhibition of vagal tone results in dilatation of large and small airways. Analysis of the flow volume results on the equal pressure point model suggests that the bronchodilatation normally resulting from the inhalation to total lung capacity is not solely due to inhibition of vagal tone.", "contents": "Effect of an inhaled atropinelike agent on normal airway function. Ten normal subjects inhaled 80 microgram ipratropium or placebo. Body plethysmograph studies showed that ipratropium increased specific conductance (0.14-0.21 s-1.cmH2O-1) and increased flow rates during both maximal and partial forced expiratory maneuvers at all volumes from 50 to 10% vital capacity (P less than 0.01). Ipratropium produced no change in quasi-static or dynamic compliance, closing volume, or the slope of phase III of the closing volume trace, but there was an increase in the height of phase IV (P less than 0.01). Specific conductance reflects central airways caliber, whereas flow rates at low lung volumes in the absence of alteration in static recoil pressure may reflect the caliber of more peripheral airways. We conclude that inhibition of vagal tone results in dilatation of large and small airways. Analysis of the flow volume results on the equal pressure point model suggests that the bronchodilatation normally resulting from the inhalation to total lung capacity is not solely due to inhibition of vagal tone."} {"id": "PMID:154493", "title": "Effect of a mild exercise program on myocardial function and the development of hypertrophy.", "content": "Cardiac function and the development of myocardial hypertrophy were studied in rats conditioned by an exercise program consisting of 8 wk of running on a treadmill. At the end of the training period a group of exercised and sedentary rats was subjected to hemodynamic evaluation under general anesthesia. Except for a slight elevation in the heart rates of the exercised animals there were no significant differences between the exercised and sedentary rats at rest. Following an increase in afterload or a period of hypoxia, the cardiac index of the exercised animals remained significantly higher than that of the sedentary controls. These differences were related to changes in stroke volume. Another group of exercised and sedentary animals underwent either constriction of the ascending aorta or a sham operation. Sedentary rats developed significant hypertrophy at 3 days but had no hypertrophy at 1 day after aortic constriction. Exercised rats, however, developed significant myocardial hypertrophy by 1 day after pressure overload. These data suggest that the heart from an exercised animal is better able to tolerate increases in afterload and hypoxia and can respond with compensatory myocardial hypertrophy more rapidly than the heart of a sedentary animal.", "contents": "Effect of a mild exercise program on myocardial function and the development of hypertrophy. Cardiac function and the development of myocardial hypertrophy were studied in rats conditioned by an exercise program consisting of 8 wk of running on a treadmill. At the end of the training period a group of exercised and sedentary rats was subjected to hemodynamic evaluation under general anesthesia. Except for a slight elevation in the heart rates of the exercised animals there were no significant differences between the exercised and sedentary rats at rest. Following an increase in afterload or a period of hypoxia, the cardiac index of the exercised animals remained significantly higher than that of the sedentary controls. These differences were related to changes in stroke volume. Another group of exercised and sedentary animals underwent either constriction of the ascending aorta or a sham operation. Sedentary rats developed significant hypertrophy at 3 days but had no hypertrophy at 1 day after aortic constriction. Exercised rats, however, developed significant myocardial hypertrophy by 1 day after pressure overload. These data suggest that the heart from an exercised animal is better able to tolerate increases in afterload and hypoxia and can respond with compensatory myocardial hypertrophy more rapidly than the heart of a sedentary animal."} {"id": "PMID:154494", "title": "Histochemical type I fibres in the soleus of the rat.", "content": "Based on oxidative enzyme activity levels, fibres exhibiting moderate and high levels may be identified in the soleus of the rat. Fibres showing moderate activity are classified as Type I fibres, while those showing high activity may belong to Type I or Type II. According to the level of ATPase activity in fixed sections, we can distinguish three types of fibres in the soleus of the rat (IA, IB and II) and, by application of acid pre-incubation, also sub-classes of Type II (IIA and IIC). Type IB fibres possess high oxidative and glycolytic enzyme activities, moderate ATPase activity after fixation, and behave in the same way as Type I fibres after alkaline and acid pre-incubation. For the histochemical classificationof fibre types, we should consider not only reactions to ATPase, and after acid pre-incubation, but also reactions to the enzymes of oxidative and glycolytic metabolism.", "contents": "Histochemical type I fibres in the soleus of the rat. Based on oxidative enzyme activity levels, fibres exhibiting moderate and high levels may be identified in the soleus of the rat. Fibres showing moderate activity are classified as Type I fibres, while those showing high activity may belong to Type I or Type II. According to the level of ATPase activity in fixed sections, we can distinguish three types of fibres in the soleus of the rat (IA, IB and II) and, by application of acid pre-incubation, also sub-classes of Type II (IIA and IIC). Type IB fibres possess high oxidative and glycolytic enzyme activities, moderate ATPase activity after fixation, and behave in the same way as Type I fibres after alkaline and acid pre-incubation. For the histochemical classificationof fibre types, we should consider not only reactions to ATPase, and after acid pre-incubation, but also reactions to the enzymes of oxidative and glycolytic metabolism."} {"id": "PMID:154495", "title": "Differences in the histochemical properties of skeletal muscles of different breeds of horses and dogs.", "content": "Histochemical profiles of individual muscle fibres were established using myosin adenosine triphosphatase (myosin ATPase), succinate dehydrogenase (SDHase), and glycogen phosphorylase (GPase) reactions in three muscles (semitendinosus, diaphragm, and pectoralis transversus) of the horse and dog. The major histochemical difference between fibres lies in their myosin ATPase activity; fibres can be subdivided into those with a high and those with a low activity. In horse muscle, all fibres have a high activity of GPase. In the diaphragm and pectoralis transversus, all fibres have a high SDHase activity, but fibres with a low activity of SDHase are also present in samples of the semitendinosus. In dog muscle, all fibres have a high SDHase activity; myosin ATPase low-reacting fibres also have a low activity of GPase. There is a greater fractional area of myosin ATPase high-reacting fibres in the pectoralis transversus and semitendinosus of thoroughbred horses and greyhounds (breeds selected for high speed running) and in the diaphragm of greyhounds. In adults this feature does not appear to be due to training, as are the differences in aerobic and anaerobic capacity (shown in other studies). The preponderance of myosin Atpase high-reacting fibres suggests that there may be differences in the nervous systems of athletes and non-athletes. It is concluded that the proportions of fibre types in muscles are related to the functions of muscles and of their parts. No sex differences or detraining effects were apparent, although the value for the proportion of fibre types (as differentiated by the myosin ATPase reaction) in the limb muscles of thoroughbred crosses lies between those of thoroughbreds and non-thoroughbreds.", "contents": "Differences in the histochemical properties of skeletal muscles of different breeds of horses and dogs. Histochemical profiles of individual muscle fibres were established using myosin adenosine triphosphatase (myosin ATPase), succinate dehydrogenase (SDHase), and glycogen phosphorylase (GPase) reactions in three muscles (semitendinosus, diaphragm, and pectoralis transversus) of the horse and dog. The major histochemical difference between fibres lies in their myosin ATPase activity; fibres can be subdivided into those with a high and those with a low activity. In horse muscle, all fibres have a high activity of GPase. In the diaphragm and pectoralis transversus, all fibres have a high SDHase activity, but fibres with a low activity of SDHase are also present in samples of the semitendinosus. In dog muscle, all fibres have a high SDHase activity; myosin ATPase low-reacting fibres also have a low activity of GPase. There is a greater fractional area of myosin ATPase high-reacting fibres in the pectoralis transversus and semitendinosus of thoroughbred horses and greyhounds (breeds selected for high speed running) and in the diaphragm of greyhounds. In adults this feature does not appear to be due to training, as are the differences in aerobic and anaerobic capacity (shown in other studies). The preponderance of myosin Atpase high-reacting fibres suggests that there may be differences in the nervous systems of athletes and non-athletes. It is concluded that the proportions of fibre types in muscles are related to the functions of muscles and of their parts. No sex differences or detraining effects were apparent, although the value for the proportion of fibre types (as differentiated by the myosin ATPase reaction) in the limb muscles of thoroughbred crosses lies between those of thoroughbreds and non-thoroughbreds."} {"id": "PMID:154508", "title": "Proton translocation in cytochrome-deficient mutants of Escherichia coli.", "content": "Cytochrome-deficient cells of a strain of Escherichia coli lacking 5-amino-levulinate synthetase have been used to study proton translocation associated with the reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase region of the electron transport chain. Menadione was used as electron acceptor, and mannitol was used as the substrate for the generation of intracellular NADH. The effects of iron deficiency on NADH- and D-lactate-menadione reductase activities were studied in iron-deficient cells of a mutant strain unable to synthesize the iron chelator enterochelin; both activities were reduced. The NADH- menadione reductase activity in cytochrome-deficient cells was associated with proton translocation and could be coupled to the uptake of proline. However proton translocation associated with the NADH-menadione reductase activity was prevented by a mutation in an unc gene. It was concluded that there is no proton translocation associated with the NADH-dehydrogenase region of the electron transport chain in E. coli and that the proton translocation obtained with mannitol as substrate is due to the activity of membrane-bound adenosine triphosphatase.", "contents": "Proton translocation in cytochrome-deficient mutants of Escherichia coli. Cytochrome-deficient cells of a strain of Escherichia coli lacking 5-amino-levulinate synthetase have been used to study proton translocation associated with the reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase region of the electron transport chain. Menadione was used as electron acceptor, and mannitol was used as the substrate for the generation of intracellular NADH. The effects of iron deficiency on NADH- and D-lactate-menadione reductase activities were studied in iron-deficient cells of a mutant strain unable to synthesize the iron chelator enterochelin; both activities were reduced. The NADH- menadione reductase activity in cytochrome-deficient cells was associated with proton translocation and could be coupled to the uptake of proline. However proton translocation associated with the NADH-menadione reductase activity was prevented by a mutation in an unc gene. It was concluded that there is no proton translocation associated with the NADH-dehydrogenase region of the electron transport chain in E. coli and that the proton translocation obtained with mannitol as substrate is due to the activity of membrane-bound adenosine triphosphatase."} {"id": "PMID:154509", "title": "A fifth gene (uncE) in the operon concerned with oxidative phosphorylation in Escherichia coli.", "content": "Three mutant unc alleles (unc-408, unc-410, and unc-429) affecting the coupling of electron transport to oxidative phosphorylation in Escherichia coli K-12 have been characterized. Genetic complementation analyses using previously defined mutant unc alleles indicated that the new mutant unc alleles affect a previously undescribed gene designated uncE. The phenotype of strains carrying the uncE408 or uncE429 allele is similar in that Mg(2+)-adenosine triphosphatase activity is only found in the cytoplasmic fraction, and membranes do not bind the F(1) portion of adenosine triphosphatase purified from a normal strain. In contrast, adenosine triphosphatase activity is present both in the cytoplasm and on the membranes from a strain carrying the unc-410 allele, and normal F(1) binds to F(1)-depleted membranes from this strain. The adenosine triphosphatase solubilized from membranes of a strain carrying the unc-410 allele reconstituted ATP-dependent membrane energization in F(1)-depleted membranes from a normal strain. Genetic complementation tests using various Mu-induced unc alleles in partial diploid strains show that the uncE gene is in the unc operon and that the order of genes is uncB E A D C. The unc-410 allele differs from the uncE408 and uncE429 alleles in that complementation tests with the Mu-induced unc alleles indicate that more than one gene is affected. It is concluded that this is due to a deletion which includes part of the uncE gene and another gene, or genes, between the uncE and uncA genes.", "contents": "A fifth gene (uncE) in the operon concerned with oxidative phosphorylation in Escherichia coli. Three mutant unc alleles (unc-408, unc-410, and unc-429) affecting the coupling of electron transport to oxidative phosphorylation in Escherichia coli K-12 have been characterized. Genetic complementation analyses using previously defined mutant unc alleles indicated that the new mutant unc alleles affect a previously undescribed gene designated uncE. The phenotype of strains carrying the uncE408 or uncE429 allele is similar in that Mg(2+)-adenosine triphosphatase activity is only found in the cytoplasmic fraction, and membranes do not bind the F(1) portion of adenosine triphosphatase purified from a normal strain. In contrast, adenosine triphosphatase activity is present both in the cytoplasm and on the membranes from a strain carrying the unc-410 allele, and normal F(1) binds to F(1)-depleted membranes from this strain. The adenosine triphosphatase solubilized from membranes of a strain carrying the unc-410 allele reconstituted ATP-dependent membrane energization in F(1)-depleted membranes from a normal strain. Genetic complementation tests using various Mu-induced unc alleles in partial diploid strains show that the uncE gene is in the unc operon and that the order of genes is uncB E A D C. The unc-410 allele differs from the uncE408 and uncE429 alleles in that complementation tests with the Mu-induced unc alleles indicate that more than one gene is affected. It is concluded that this is due to a deletion which includes part of the uncE gene and another gene, or genes, between the uncE and uncA genes."} {"id": "PMID:154510", "title": "Selection of succinic dehydrogenase mutants of Neurospora crassa.", "content": "A method is described which permits the selection of mutants of Neurospora crassa that are deficient in succinic dehydrogenase activity. The method relies on the observation that succinic dehydrogenase-deficient strains fail to reduce the dye nitrotetrazolium blue when overlaid with the dye in the presence of succinate and phenazine methosulfate. Wild-type colonies reduced the dye and turned blue, whereas mutant colonies remained colorless. In this communication we present studies of a mutant, SDH-1, isolated by this method. The mutant had 18% of the succinic dehydrogenase activity of the parent strain used in the mutation experiments as determined from the ratio of Vmax activities obtained from Lineweaver-Burk plots. The SDH-1 mutant segregated in a Mendelian manner when back-crossed to its parent strain. Succinate oxidase activity in SDH-1 was low and was markedly inhibited by adenosine 5'-diphosphate. The succinate oxidase activity of the parent strain was high and was not affected by the presence of adenosine 5'-diphosphate.", "contents": "Selection of succinic dehydrogenase mutants of Neurospora crassa. A method is described which permits the selection of mutants of Neurospora crassa that are deficient in succinic dehydrogenase activity. The method relies on the observation that succinic dehydrogenase-deficient strains fail to reduce the dye nitrotetrazolium blue when overlaid with the dye in the presence of succinate and phenazine methosulfate. Wild-type colonies reduced the dye and turned blue, whereas mutant colonies remained colorless. In this communication we present studies of a mutant, SDH-1, isolated by this method. The mutant had 18% of the succinic dehydrogenase activity of the parent strain used in the mutation experiments as determined from the ratio of Vmax activities obtained from Lineweaver-Burk plots. The SDH-1 mutant segregated in a Mendelian manner when back-crossed to its parent strain. Succinate oxidase activity in SDH-1 was low and was markedly inhibited by adenosine 5'-diphosphate. The succinate oxidase activity of the parent strain was high and was not affected by the presence of adenosine 5'-diphosphate."} {"id": "PMID:154511", "title": "Circadian rhythms in Neurospora crassa: effects of unsaturated fatty acids.", "content": "Employing a fatty acid-requiring strain (bd csp cel) of Neurospora crassa, the 21.5-h period of the circadian spore-forming rhythm was manipulated by fatty acid supplementation. The addition to the medium of an unsaturated fatty acid (oleic, linoleic, or linolenic acid) lengthened the period to 26, 40, or 33 h, respectively. Ther period-lengthening effect of linoleic acid was proportional to its concentration up to 1.3 X 10(-4) M, and also was reversed by the addition to the medium of a saturated fatty acid, palmitic acid. None of these period-lengthening effects was observed in the prototrophic strain (bd csp cel+).", "contents": "Circadian rhythms in Neurospora crassa: effects of unsaturated fatty acids. Employing a fatty acid-requiring strain (bd csp cel) of Neurospora crassa, the 21.5-h period of the circadian spore-forming rhythm was manipulated by fatty acid supplementation. The addition to the medium of an unsaturated fatty acid (oleic, linoleic, or linolenic acid) lengthened the period to 26, 40, or 33 h, respectively. Ther period-lengthening effect of linoleic acid was proportional to its concentration up to 1.3 X 10(-4) M, and also was reversed by the addition to the medium of a saturated fatty acid, palmitic acid. None of these period-lengthening effects was observed in the prototrophic strain (bd csp cel+)."} {"id": "PMID:154512", "title": "Identification of myosin in a flowering plant, Egeria densa.", "content": "A myosin-like protein was extracted and partially purified from a flowering plant, Egeria densa. It had no p-nitrophenyl phosphatase activity, but exhibited EDTA(K+)-ATPase [EC 3.6.1.3] activity at high ionic strength. Its molecular weight as estimated by gel filtration was 4-5 X 10(5). The presence of a heavy chain (MW = about 1.8 X 10(5)) was indicated by SDS-gel electrophoresis. Egeria myosin aggregated in an environment of low ionic strength and formed bipolar filaments. It bound with skeletal muscle F-actin with a periodicity of 40 nm.", "contents": "Identification of myosin in a flowering plant, Egeria densa. A myosin-like protein was extracted and partially purified from a flowering plant, Egeria densa. It had no p-nitrophenyl phosphatase activity, but exhibited EDTA(K+)-ATPase [EC 3.6.1.3] activity at high ionic strength. Its molecular weight as estimated by gel filtration was 4-5 X 10(5). The presence of a heavy chain (MW = about 1.8 X 10(5)) was indicated by SDS-gel electrophoresis. Egeria myosin aggregated in an environment of low ionic strength and formed bipolar filaments. It bound with skeletal muscle F-actin with a periodicity of 40 nm."} {"id": "PMID:154513", "title": "Chicken gizzard heavy meromyosin that retains the two light-chain components, including a phosphorylatable one.", "content": "A method was developed to obtain a preparation of chicken gizzard heavy meromyosin (HMM) that retains the two light-chain components of parent myosin: the 20,000-dalton and 17,000-dalton light-chains. The HMM preparation was also shown to retain two characteristics of the ATPase activity of the parent myosin: the characteristic effect of phosphorylation of the 20,000-dalton light-chain component on the ATPase activity, and the characteristic dependence of the ATPase activity on the KCl concentration. 1. Two distinct stages were observed in the Mg-ATPase reaction catalyzed by gizzard HMM and rabbit skeletal actin in the presence of gizzard \"native\" tropomyosin (NTM) and Ca2+ ions: an early lag phase, in which the reaction rate gradually increased, and a subsequent steady state, in which the reaction proceeded at a high, constant rate. Urea-gel electrophoresis revealed that the 20,000-dalton light-chain component was gradually phosphorylated in the lag phase, and was fully phosphorylated in the steady state. It was also observed that addition of EGTA (to remove Ca2+ ions) at various times in the lag phase caused neither a further increase nor a decrease in the reaction rate, and that addition of EGTA in the steady state caused no change in the reaction rate. These observations imply that the ATPase activity increased as the amount of phosphorylated 20,000-dalton light-chain component increased, and also that Mg-ATPase of acto-phosphorylated HMM was no longer calcium-sensitive. 2. The Mg-ATPase activity of HMM in the presence of gizzard NTM and Ca2+ ions or EGTA was studied as a function of the concentration of rabbit skeletal actin. The maximal activity (Vmax) and the apparent affinity constant of acto-HMM (KA) were thus estimated from the double-reciprocal plot of Eisenberg-Moos: the Vmax and KA values for phosphorylated HMM (in the presence of Ca2+ ions) were 5 S(-1) and 5.5 mg/ml actin, respectively, and the Vmax value for unphosphorylated HMM (in the presence of EGTA) was 0.3 S(-1), assuming that the KA value with unphosphorylated HMM is equal to that with phosphorylated HMM.", "contents": "Chicken gizzard heavy meromyosin that retains the two light-chain components, including a phosphorylatable one. A method was developed to obtain a preparation of chicken gizzard heavy meromyosin (HMM) that retains the two light-chain components of parent myosin: the 20,000-dalton and 17,000-dalton light-chains. The HMM preparation was also shown to retain two characteristics of the ATPase activity of the parent myosin: the characteristic effect of phosphorylation of the 20,000-dalton light-chain component on the ATPase activity, and the characteristic dependence of the ATPase activity on the KCl concentration. 1. Two distinct stages were observed in the Mg-ATPase reaction catalyzed by gizzard HMM and rabbit skeletal actin in the presence of gizzard \"native\" tropomyosin (NTM) and Ca2+ ions: an early lag phase, in which the reaction rate gradually increased, and a subsequent steady state, in which the reaction proceeded at a high, constant rate. Urea-gel electrophoresis revealed that the 20,000-dalton light-chain component was gradually phosphorylated in the lag phase, and was fully phosphorylated in the steady state. It was also observed that addition of EGTA (to remove Ca2+ ions) at various times in the lag phase caused neither a further increase nor a decrease in the reaction rate, and that addition of EGTA in the steady state caused no change in the reaction rate. These observations imply that the ATPase activity increased as the amount of phosphorylated 20,000-dalton light-chain component increased, and also that Mg-ATPase of acto-phosphorylated HMM was no longer calcium-sensitive. 2. The Mg-ATPase activity of HMM in the presence of gizzard NTM and Ca2+ ions or EGTA was studied as a function of the concentration of rabbit skeletal actin. The maximal activity (Vmax) and the apparent affinity constant of acto-HMM (KA) were thus estimated from the double-reciprocal plot of Eisenberg-Moos: the Vmax and KA values for phosphorylated HMM (in the presence of Ca2+ ions) were 5 S(-1) and 5.5 mg/ml actin, respectively, and the Vmax value for unphosphorylated HMM (in the presence of EGTA) was 0.3 S(-1), assuming that the KA value with unphosphorylated HMM is equal to that with phosphorylated HMM."} {"id": "PMID:154514", "title": "Myosin from abdominal flexor muscle in a crayfish, Procambarus clarki Girard.", "content": "1. Crayfish (Procambarus clarki) myosin was obtained from abdominal flexor muscle. The Ca2+-ATPase activity of crayfish myosin was much lower than that of rabbit skeletal myosin. However, F-actin-activated Mg2+-ATPase of crayfish and its superprecipitation closely resembled those of rabbit skeletal myosin. This fact suggests that the ability of crayfish myosin to combine with F-actin is essentially the same as that of skeletal myosin, although the chemical structures of both the myosin molecules when involved in their Ca2+-ATPast activity must be different from each other. 2. Crayfish and rabbit skeletal myosins were subjected to SDS-polyacrylamide gel electrophoresis. Crayfish myosin was found to have one heavy chain and two distinct light chain components (CF-gl and CF-g2), which have molecular weights of 18,000 and 16,000, respectively. These light chains correspond in molecular weight to the light chains (SK-g2 and SK-g3) in rabbit skeletal myosin. 3. CF-g1 could be liberated from the crayfish myosin molecule reacting with 5,5'-dithio-bis (2-nitrobenzoic acid), (Nbs2), without recovery of ATPase activity by the addition of DTT. These properties are equivalent to those of SK-g2 in rabbit skeletal myosin, although Nbs2-treated crayfish myosin did not recover its ATPase activity at all.", "contents": "Myosin from abdominal flexor muscle in a crayfish, Procambarus clarki Girard. 1. Crayfish (Procambarus clarki) myosin was obtained from abdominal flexor muscle. The Ca2+-ATPase activity of crayfish myosin was much lower than that of rabbit skeletal myosin. However, F-actin-activated Mg2+-ATPase of crayfish and its superprecipitation closely resembled those of rabbit skeletal myosin. This fact suggests that the ability of crayfish myosin to combine with F-actin is essentially the same as that of skeletal myosin, although the chemical structures of both the myosin molecules when involved in their Ca2+-ATPast activity must be different from each other. 2. Crayfish and rabbit skeletal myosins were subjected to SDS-polyacrylamide gel electrophoresis. Crayfish myosin was found to have one heavy chain and two distinct light chain components (CF-gl and CF-g2), which have molecular weights of 18,000 and 16,000, respectively. These light chains correspond in molecular weight to the light chains (SK-g2 and SK-g3) in rabbit skeletal myosin. 3. CF-g1 could be liberated from the crayfish myosin molecule reacting with 5,5'-dithio-bis (2-nitrobenzoic acid), (Nbs2), without recovery of ATPase activity by the addition of DTT. These properties are equivalent to those of SK-g2 in rabbit skeletal myosin, although Nbs2-treated crayfish myosin did not recover its ATPase activity at all."} {"id": "PMID:154518", "title": "Optical probe responses on sarcoplasmic reticulum. Oxacarbocyanines.", "content": "Absorbance and fluorescence changes of oxacarbocyanine dyes during ATP-induced Ca2+ transport in rabbit sarcoplasmic reticulum were analyzed. The response of the probes is complex and contains contributions from the binding of Ca2+ and ATP to the membrane. In a medium of 0.12 M KCl and 5 mM MgCl2, the fluorescence of Di-O-C5(3) is decreased by Ca2+ or ATP with apparent dissociation constants of 0.2 and 5 micron, respectively. This suggests that oxacarbocyanines respond to binding of Ca2+ and ATP at the active site of Ca2+ transport ATPase. The effect of ATP is observed in the absence of divalent cations. Further changes in the fluorescence or absorbance of cyanine dyes occur at millimolar concentrations of Ca2+ or during ATP-induced Ca2+ uptake, which can be related to Ca2+ binding to low affinity, relatively nonspecific binding sites on the membrane, that can also bind K+ and Mg2+. The optical changes due to Ca2+ accumulation are most pronounced in media of 0.25 M sucrose and much reduced in 0.12 M KCl and 5 mM MgCl2, in accord with competition by K+ and Mg2+ for the low affinity Ca2+ binding sites. These effects must be taken into account in the evaluation of the magnitude and direction of membrane potential in sarcoplasmic reticulum vesicles during Ca2+ uptake and release.", "contents": "Optical probe responses on sarcoplasmic reticulum. Oxacarbocyanines. Absorbance and fluorescence changes of oxacarbocyanine dyes during ATP-induced Ca2+ transport in rabbit sarcoplasmic reticulum were analyzed. The response of the probes is complex and contains contributions from the binding of Ca2+ and ATP to the membrane. In a medium of 0.12 M KCl and 5 mM MgCl2, the fluorescence of Di-O-C5(3) is decreased by Ca2+ or ATP with apparent dissociation constants of 0.2 and 5 micron, respectively. This suggests that oxacarbocyanines respond to binding of Ca2+ and ATP at the active site of Ca2+ transport ATPase. The effect of ATP is observed in the absence of divalent cations. Further changes in the fluorescence or absorbance of cyanine dyes occur at millimolar concentrations of Ca2+ or during ATP-induced Ca2+ uptake, which can be related to Ca2+ binding to low affinity, relatively nonspecific binding sites on the membrane, that can also bind K+ and Mg2+. The optical changes due to Ca2+ accumulation are most pronounced in media of 0.25 M sucrose and much reduced in 0.12 M KCl and 5 mM MgCl2, in accord with competition by K+ and Mg2+ for the low affinity Ca2+ binding sites. These effects must be taken into account in the evaluation of the magnitude and direction of membrane potential in sarcoplasmic reticulum vesicles during Ca2+ uptake and release."} {"id": "PMID:154521", "title": "Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina.", "content": "Midline prolapse of a disc causing compression of the cauda equina is rare but needs urgent diagnosis and surgical treatment. The onset of bladder and rectal paralysis with saddle anaesthesia should be viewed with a high index of suspicion in a patient with backache and sciatica. Eight cases were seen over a period of five years, and they fell into three clinical groups. Group I patients presented with a sudden onset without any previous symptoms related to the back. Group II patients had a history of recurrent episodes of backache and sciatica, the latest episode resulting in involvement of the cauda equina. The group III patient was indistinguishable from one with a tumour as he presented with backache and sciatica slowly progressing to paralysis of the cauda equina. The prolapse was at the disc between L5 and S1 vertebrae in 50 per cent of the patients, most of whom did not have any limitation of straight leg raising. Urgent myelography and equally urgent removal of the disc within two weeks of the onset of the symptoms resulted in almost complete motor and bladder recovery within five months after the operation in most cases. However, recovery of sensation and sexual function was incomplete even four years after the operation.", "contents": "Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. Midline prolapse of a disc causing compression of the cauda equina is rare but needs urgent diagnosis and surgical treatment. The onset of bladder and rectal paralysis with saddle anaesthesia should be viewed with a high index of suspicion in a patient with backache and sciatica. Eight cases were seen over a period of five years, and they fell into three clinical groups. Group I patients presented with a sudden onset without any previous symptoms related to the back. Group II patients had a history of recurrent episodes of backache and sciatica, the latest episode resulting in involvement of the cauda equina. The group III patient was indistinguishable from one with a tumour as he presented with backache and sciatica slowly progressing to paralysis of the cauda equina. The prolapse was at the disc between L5 and S1 vertebrae in 50 per cent of the patients, most of whom did not have any limitation of straight leg raising. Urgent myelography and equally urgent removal of the disc within two weeks of the onset of the symptoms resulted in almost complete motor and bladder recovery within five months after the operation in most cases. However, recovery of sensation and sexual function was incomplete even four years after the operation."} {"id": "PMID:154522", "title": "Scheuermann's disease or spinal osteochondrosis: its frequency and relationship with spondylosis.", "content": "Spinal osteochondrosis, previously known as Scheuermann's disease and spinal osteochondritis, is common and is probably becoming increasingly prevalent. Its incidence in patients whose primary complaint was of backache was shown to be twice as great as that in the general population. There was also a significantly higher incidence of lower lumbar spondylosis in patients with previous osteochondrosis compared with those without. Osteochondrosis is thereby shown to be an important aetiological factor in spondylosis.", "contents": "Scheuermann's disease or spinal osteochondrosis: its frequency and relationship with spondylosis. Spinal osteochondrosis, previously known as Scheuermann's disease and spinal osteochondritis, is common and is probably becoming increasingly prevalent. Its incidence in patients whose primary complaint was of backache was shown to be twice as great as that in the general population. There was also a significantly higher incidence of lower lumbar spondylosis in patients with previous osteochondrosis compared with those without. Osteochondrosis is thereby shown to be an important aetiological factor in spondylosis."} {"id": "PMID:154523", "title": "Structure, protein composition and birefringence of the costa: a motile flagellar root fibre in the flagellate Trichomonas.", "content": "The costa is a rod-shaped intracellular organelle lying in the cytoplasm immediately below the undulating membrane. In certain large species of Trichomonas (T. gigantea, T. termopsidis and an undescribed species from the termite Porotermes adamsoni) this organelle is motile. Bending waves are transmitted along the length of the costa, in either direction. It is shown that the bending is actively produced by the costa itself. The form of the movements is described in detail. The costa is birefringent. At the point at which bending occurs there is a sharply localized reduction in birefringence. Electron microscopy shows that the costa is composed of longitudinally running lamellae, 2--3 nm thick and spaced 12 nm apart. These are connected to transversely running elements spaced at intervals of about 37 nm. The lamellae occur in two alternative configurations: straight and zig-zag. Bending probably results from a local, transient change from the straight to the zig-zag configuration. This would account for the local change in birefringence which accompanies bending. Polyacrylamide gel electrophoresis of isolated costas shows them to contain a number of protein components, of which the principal one has a molecular weight of about 90,000. Preliminary cytochemical evidence is presented for ATPase activity in the costa. The costa is a type of motile system distinct from any hitherto described.", "contents": "Structure, protein composition and birefringence of the costa: a motile flagellar root fibre in the flagellate Trichomonas. The costa is a rod-shaped intracellular organelle lying in the cytoplasm immediately below the undulating membrane. In certain large species of Trichomonas (T. gigantea, T. termopsidis and an undescribed species from the termite Porotermes adamsoni) this organelle is motile. Bending waves are transmitted along the length of the costa, in either direction. It is shown that the bending is actively produced by the costa itself. The form of the movements is described in detail. The costa is birefringent. At the point at which bending occurs there is a sharply localized reduction in birefringence. Electron microscopy shows that the costa is composed of longitudinally running lamellae, 2--3 nm thick and spaced 12 nm apart. These are connected to transversely running elements spaced at intervals of about 37 nm. The lamellae occur in two alternative configurations: straight and zig-zag. Bending probably results from a local, transient change from the straight to the zig-zag configuration. This would account for the local change in birefringence which accompanies bending. Polyacrylamide gel electrophoresis of isolated costas shows them to contain a number of protein components, of which the principal one has a molecular weight of about 90,000. Preliminary cytochemical evidence is presented for ATPase activity in the costa. The costa is a type of motile system distinct from any hitherto described."} {"id": "PMID:154524", "title": "On the reduced intercellular adhesiveness of virally transformed BHK21 cells.", "content": "Baby hamster kidney fibroblasts (BHK21 cells) transformed by polyoma or Rous sarcoma viruses aggregate less than the untransformed parental cells when incubated in growth medium in a gyratory shaker for 18-24 h. This difference can be measured by electronic particle counting, or by filtering aggregated suspensions of 32P-labelled cells through bolting fabric. The aggregation of transformed derivatives is not enhanced by the presence, during aggregation of epsilon-amino caproic acid, an inhibitor of plasmin activation. Some lines of transformed BHK21 cells do not appear less adhesive than untransformed cells in a short-term aggregation assay, and none adheres markedly less well when seeded onto homotypic cell sheets. The decreased aggregation of transformed cells is consistent with suggestions that LETS protein is involved in intercellular adhesion of fibroblasts as well as in attachment of cells to non-cellular substrates. If so, the short-term aggregation of freshly trypsinized cells may depend on secretion of LETS from an intracellular pool.", "contents": "On the reduced intercellular adhesiveness of virally transformed BHK21 cells. Baby hamster kidney fibroblasts (BHK21 cells) transformed by polyoma or Rous sarcoma viruses aggregate less than the untransformed parental cells when incubated in growth medium in a gyratory shaker for 18-24 h. This difference can be measured by electronic particle counting, or by filtering aggregated suspensions of 32P-labelled cells through bolting fabric. The aggregation of transformed derivatives is not enhanced by the presence, during aggregation of epsilon-amino caproic acid, an inhibitor of plasmin activation. Some lines of transformed BHK21 cells do not appear less adhesive than untransformed cells in a short-term aggregation assay, and none adheres markedly less well when seeded onto homotypic cell sheets. The decreased aggregation of transformed cells is consistent with suggestions that LETS protein is involved in intercellular adhesion of fibroblasts as well as in attachment of cells to non-cellular substrates. If so, the short-term aggregation of freshly trypsinized cells may depend on secretion of LETS from an intracellular pool."} {"id": "PMID:154525", "title": "Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone.", "content": "This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.", "contents": "Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone. This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation."} {"id": "PMID:154526", "title": "Inflammatory seborrheic keratoses with mononuclear cell infiltration.", "content": "Inflammation in inflammatory seborrheic keratoses was found to be composed of mononuclear cells, particularly lymphocytes. Accumulations of mononuclear cells in the papillary and subpapillary dermis frequently showed no tendency to infiltrate the epithelium. However, dramatic interaction of the seborrheic keratosis and the inflammatory process also was common. The lymphocytic exocytosis into the epithelium followed two basic patterns: eczematous, characterized by intercellular and intracellular edema, microvesicle formation, and epithelial necrosis; and lichenoid, in which a bandlike infiltrate attacked the dermoepidermal junction and hyaline bodies occurred in the infiltrated epithelium and in the dermis. Epithelial changes consisted of necrosis of epithelial cells and related parakeratosis; squamous eddies were occasionally found. Inflammatory cell infiltration in seborrheic keratoses possibly represents a process other than irritation, and we propose that mononuclear cell infiltration in seborrheic keratoses may be related to an involutionary process.", "contents": "Inflammatory seborrheic keratoses with mononuclear cell infiltration. Inflammation in inflammatory seborrheic keratoses was found to be composed of mononuclear cells, particularly lymphocytes. Accumulations of mononuclear cells in the papillary and subpapillary dermis frequently showed no tendency to infiltrate the epithelium. However, dramatic interaction of the seborrheic keratosis and the inflammatory process also was common. The lymphocytic exocytosis into the epithelium followed two basic patterns: eczematous, characterized by intercellular and intracellular edema, microvesicle formation, and epithelial necrosis; and lichenoid, in which a bandlike infiltrate attacked the dermoepidermal junction and hyaline bodies occurred in the infiltrated epithelium and in the dermis. Epithelial changes consisted of necrosis of epithelial cells and related parakeratosis; squamous eddies were occasionally found. Inflammatory cell infiltration in seborrheic keratoses possibly represents a process other than irritation, and we propose that mononuclear cell infiltration in seborrheic keratoses may be related to an involutionary process."} {"id": "PMID:154527", "title": "Transformation of seborrheic keratosis into Bowen's disease.", "content": "This case proves the possibility of a malignant transformation of seborrheic keratosis. This evidence is furnished by a biopsy specimen that shows not only a topical relationship between seborrheic keratosis and Bowen's disease, but also the progressive transition. An evident biopsy has to be made prior to clinical suspicion of malignant degeneration, that means prior to the destruction of the transitional zone by the tumor.", "contents": "Transformation of seborrheic keratosis into Bowen's disease. This case proves the possibility of a malignant transformation of seborrheic keratosis. This evidence is furnished by a biopsy specimen that shows not only a topical relationship between seborrheic keratosis and Bowen's disease, but also the progressive transition. An evident biopsy has to be made prior to clinical suspicion of malignant degeneration, that means prior to the destruction of the transitional zone by the tumor."} {"id": "PMID:154528", "title": "Ultrastructural identification of Langerhans cells in seborrheic keratoses.", "content": "Lesions of seborrheic keratoses studied by transmission electron microscopy showed an unusually large number of Langerhans cells in the epidermis. The role of Langerhans cells in the development of these lesions needs further study.", "contents": "Ultrastructural identification of Langerhans cells in seborrheic keratoses. Lesions of seborrheic keratoses studied by transmission electron microscopy showed an unusually large number of Langerhans cells in the epidermis. The role of Langerhans cells in the development of these lesions needs further study."} {"id": "PMID:154535", "title": "Hospitals for the mentally ill and handicapped in Melbourne Australia.", "content": "This report of visits made while on a Churchill Traveling Fellowship briefly outlines some catering problems in caring for the mentally ill and handicapped.", "contents": "Hospitals for the mentally ill and handicapped in Melbourne Australia. This report of visits made while on a Churchill Traveling Fellowship briefly outlines some catering problems in caring for the mentally ill and handicapped."} {"id": "PMID:154536", "title": "Autoimmune interaction measured in a postlabelling microcytostasis assay.", "content": "A postlabelling microcytostasis assay was developed to assess primary immune interaction between normal rat lymphocytes and autologous testis cells. In this vitro model of experimental autoimmune orchitis (EAO) unprimed T cells respond to a Sertoli-like subpopulation of testis cells during a 4 day culture period. The T effector cells exert a cytostatic effect on the monolayer-forming target cells. The number of remaining target cells, which inversely correlates with the intensity of the autoimmune reaction, is quantified by 51Cr incorporation. The assay is performed in multiple well plastic plates which allow rapid harvesting by cutting off the bottoms of each well. The attached labelled target cells are directly measured on the bottoms without any further transfer step. The method is adapted for the EAO model but may be useful to study primary T cell interaction with any other monolayer-forming target cells.", "contents": "Autoimmune interaction measured in a postlabelling microcytostasis assay. A postlabelling microcytostasis assay was developed to assess primary immune interaction between normal rat lymphocytes and autologous testis cells. In this vitro model of experimental autoimmune orchitis (EAO) unprimed T cells respond to a Sertoli-like subpopulation of testis cells during a 4 day culture period. The T effector cells exert a cytostatic effect on the monolayer-forming target cells. The number of remaining target cells, which inversely correlates with the intensity of the autoimmune reaction, is quantified by 51Cr incorporation. The assay is performed in multiple well plastic plates which allow rapid harvesting by cutting off the bottoms of each well. The attached labelled target cells are directly measured on the bottoms without any further transfer step. The method is adapted for the EAO model but may be useful to study primary T cell interaction with any other monolayer-forming target cells."} {"id": "PMID:154537", "title": "An estimate of the minimal frequency of cytolytic T lymphocyte effector cells generated in allogeneic reactions.", "content": "A 'micro' modification of the standard 51Cr release assay was developed. With this assay, significant cytolysis was obtained employing 100--200 51Cr-labeled target cells and fewer than 100 lymphocytes obtained from mixed leukocyte cultures. A minimal estimate as to the actual frequency of effector cells was determined for both primary (1 cell in 30) and secondary (1 cells in 8) cytolytic T lymphocyte populations.", "contents": "An estimate of the minimal frequency of cytolytic T lymphocyte effector cells generated in allogeneic reactions. A 'micro' modification of the standard 51Cr release assay was developed. With this assay, significant cytolysis was obtained employing 100--200 51Cr-labeled target cells and fewer than 100 lymphocytes obtained from mixed leukocyte cultures. A minimal estimate as to the actual frequency of effector cells was determined for both primary (1 cell in 30) and secondary (1 cells in 8) cytolytic T lymphocyte populations."} {"id": "PMID:154538", "title": "Cross-linking of the (Ca2+ + Mg2+)-ATPase protein.", "content": "The addition of cupric-1,10,-phenanthroline, a cross-linking catalyst, to sarcoplasmic reticulum membranes caused protein sulfhydryl groups to form disulfide bridges. Following a short exposure to the catalyst (15 s, 22 degrees C) most of the protein was in a dimeric form (Mr = 248,000). Longer exposure times resulted in the formation of trimers, tetramers and other oligomers too large to enter the gel. At low temperatures (4 degrees C) dimer formation predominates, even for exposure times as long as 5 min. Cross-linking in the presence of 7.5 mM Triton X-100 (a concentration that resulted in clearing of the membrane suspension and thus solubilization of the membrane components) showed the appearance of a considerable dimer fraction, however, most of the (Ca2+ + Mg2+)-ATPase protein appeared as a monomer. Following 1 min of cross-linking at 22 degrees C, freeze-etched membranes showed no alteration in the number or appearance of 80 A intramembranous particles. Thus extensive cross-linking of the (Ca2+ + Mg2+)-ATPase protein can occur without disruption of the normal position of the intramembrane portion of the molecule.", "contents": "Cross-linking of the (Ca2+ + Mg2+)-ATPase protein. The addition of cupric-1,10,-phenanthroline, a cross-linking catalyst, to sarcoplasmic reticulum membranes caused protein sulfhydryl groups to form disulfide bridges. Following a short exposure to the catalyst (15 s, 22 degrees C) most of the protein was in a dimeric form (Mr = 248,000). Longer exposure times resulted in the formation of trimers, tetramers and other oligomers too large to enter the gel. At low temperatures (4 degrees C) dimer formation predominates, even for exposure times as long as 5 min. Cross-linking in the presence of 7.5 mM Triton X-100 (a concentration that resulted in clearing of the membrane suspension and thus solubilization of the membrane components) showed the appearance of a considerable dimer fraction, however, most of the (Ca2+ + Mg2+)-ATPase protein appeared as a monomer. Following 1 min of cross-linking at 22 degrees C, freeze-etched membranes showed no alteration in the number or appearance of 80 A intramembranous particles. Thus extensive cross-linking of the (Ca2+ + Mg2+)-ATPase protein can occur without disruption of the normal position of the intramembrane portion of the molecule."} {"id": "PMID:154539", "title": "HLA-antigens and contact hypersensitivity.", "content": "The HLA-A, -B -C typing of 100 bricklayers was performed. 50 bricklayers had developed contact allergy to chromium while 50 were healthy bricklayers. The distribution of HLA antigens were equal in the 2 groups.", "contents": "HLA-antigens and contact hypersensitivity. The HLA-A, -B -C typing of 100 bricklayers was performed. 50 bricklayers had developed contact allergy to chromium while 50 were healthy bricklayers. The distribution of HLA antigens were equal in the 2 groups."} {"id": "PMID:154533", "title": "[Tuberculosis of the uterus and adnexae. A retrospective study that has lasted 20 years (author's transl)].", "content": "The frequency of tuberculosis has considerably lessened and its localisation in the female genital organs has benefited by this happy result of immunisation by B.C.G. We have had 60 cases and carried out an analytical study on them and compared them with those of other authors. Great progress in therapy has allowed us to plan a coherent attitude by taking note of the normal way in which tuberculosis evolves and the correct measures for treating it in the uterus and adnexae.", "contents": "[Tuberculosis of the uterus and adnexae. A retrospective study that has lasted 20 years (author's transl)]. The frequency of tuberculosis has considerably lessened and its localisation in the female genital organs has benefited by this happy result of immunisation by B.C.G. We have had 60 cases and carried out an analytical study on them and compared them with those of other authors. Great progress in therapy has allowed us to plan a coherent attitude by taking note of the normal way in which tuberculosis evolves and the correct measures for treating it in the uterus and adnexae."} {"id": "PMID:154540", "title": "Use of allograft amniotic membrane for control of intra-abdominal adhesions.", "content": "The authors have studied 60 rabbits to determine the effect and fate of allograft amniotic membranes (devoid of chorion) used in the intra-peritoneal cavity to control adhesions secondary to bowel perforation and bacterial contamination. The experimental animals revealed dramatic differences when compared to the control with major reduction in adhesions. Abscesses remained localized and contained. No untoward reactions were noted in the host. Violent immunologic rejection did not occur. The membranes gradually disintegrated and left little or no evidence of its presence. Important clinical applications are obvious.", "contents": "Use of allograft amniotic membrane for control of intra-abdominal adhesions. The authors have studied 60 rabbits to determine the effect and fate of allograft amniotic membranes (devoid of chorion) used in the intra-peritoneal cavity to control adhesions secondary to bowel perforation and bacterial contamination. The experimental animals revealed dramatic differences when compared to the control with major reduction in adhesions. Abscesses remained localized and contained. No untoward reactions were noted in the host. Violent immunologic rejection did not occur. The membranes gradually disintegrated and left little or no evidence of its presence. Important clinical applications are obvious."} {"id": "PMID:154541", "title": "Adenosine deaminase levels in construction workers with asbestos contact dermatitis.", "content": "Adenosine deaminase (ADA) activity was measured in the lymphocytes, red blood cells and plasma of twelve construction workers with cutaneous hypersensitivity reactions to asbestos. Lymphocyte ADA activity was significantly greater in exposed individuals than a control population (p less than 0.0001), whereas erythrocyte and plasma enzyme activity did not differ from control determinations. ADA catalyzes the conversion of adenosine to inosine. Since increased adenosine concentrations in tissue culture inhibit the growth of lymphoblastic cell lines, it has been postulated that decreased ADA activity can result in suppression of the immune response by the inhibition of cell division. Our results indicate that the converse also applies, such that an increase in lymphocyte ADA activity may reflect an increased immune response.", "contents": "Adenosine deaminase levels in construction workers with asbestos contact dermatitis. Adenosine deaminase (ADA) activity was measured in the lymphocytes, red blood cells and plasma of twelve construction workers with cutaneous hypersensitivity reactions to asbestos. Lymphocyte ADA activity was significantly greater in exposed individuals than a control population (p less than 0.0001), whereas erythrocyte and plasma enzyme activity did not differ from control determinations. ADA catalyzes the conversion of adenosine to inosine. Since increased adenosine concentrations in tissue culture inhibit the growth of lymphoblastic cell lines, it has been postulated that decreased ADA activity can result in suppression of the immune response by the inhibition of cell division. Our results indicate that the converse also applies, such that an increase in lymphocyte ADA activity may reflect an increased immune response."} {"id": "PMID:154542", "title": "Flutter and fibrillation-like phenomenon of His bundle observed in a patient with persistent atrial standstill.", "content": "A diagnosis of persistent atrial standstill was made in a patient with syncopal attacks, based on: (1) the lack of P waves both in the routine 12-lead electrocardiogram (ECG) and in the right atrial cavity lead; (2) the absence of \"a waves in the right atrial pressure curve; and (3) the failure of the atria to respond to electrical stimulation. Compared with previously reported cases of persistent atrial standstill with a slow, regular escape rhythm of supraventricular origin, the present case was characterized by alternate periods of bradycardia and tachycardia, the latter being suggested as AV junctional tachycardia with exit block. Furthermore, the His bundle electrogram (HBE) showed either regular, high frequency deflictions or irregular, deformed potentials, suggesting flutter and fibrillation-like phenomena in the His bundle.", "contents": "Flutter and fibrillation-like phenomenon of His bundle observed in a patient with persistent atrial standstill. A diagnosis of persistent atrial standstill was made in a patient with syncopal attacks, based on: (1) the lack of P waves both in the routine 12-lead electrocardiogram (ECG) and in the right atrial cavity lead; (2) the absence of \"a waves in the right atrial pressure curve; and (3) the failure of the atria to respond to electrical stimulation. Compared with previously reported cases of persistent atrial standstill with a slow, regular escape rhythm of supraventricular origin, the present case was characterized by alternate periods of bradycardia and tachycardia, the latter being suggested as AV junctional tachycardia with exit block. Furthermore, the His bundle electrogram (HBE) showed either regular, high frequency deflictions or irregular, deformed potentials, suggesting flutter and fibrillation-like phenomena in the His bundle."} {"id": "PMID:154543", "title": "Electrocardiographic poor R wave progression. I: correlation with the Frank vectorcardiogram.", "content": "Fifty-six patients with \"poor R wave progression\" (PRWP) on the electrocardiogram (ECG) were studied by Frank vectorcardiography in an attempt to define discriminators for subgroups. Criteria were prospectively applied to a test group with achievement of comparable sensitivity and specificity. Four subgroups were identified in the patients with PRWP: Group I - anterior myocardial infarction (AMI) (20/56, 35%); Group II - left ventricular hypertrophy (LVH) (8/56, 14%); Group III - right ventricular hypertrophy (RVH) (7/56, 13%); AND Group IV - leftward axis (LA) (21/56, 38%). The best discriminator for vectorcardiogram (VCG) AMI was RV3 less than or equal to 1.5mm or R1 less than or equal to 4.0mm (18/20, 90% sensitivity; 26/36, 72% specificity). RVH and LVH were identified by R1 less than or equal to 4.0mm and S1 greater than or equal to 1.0mm and standard LVH voltage criteria respectively. Group IV patients (PRWP without VCG criteria for AMI, LVH or RVH) were identified by exclusion. \"Reversed R wave progression\" (RRWP) was more specific for AMI than was simple PRWP. The same discriminators, however, were applicable. It is clinically useful to note that 72% (26/36) of patients with either PRWP or RRWP who did not exhibit VCG AMI could be identified by 12 lead ECG with only 2/28 (7%) VCG false negative AMI.", "contents": "Electrocardiographic poor R wave progression. I: correlation with the Frank vectorcardiogram. Fifty-six patients with \"poor R wave progression\" (PRWP) on the electrocardiogram (ECG) were studied by Frank vectorcardiography in an attempt to define discriminators for subgroups. Criteria were prospectively applied to a test group with achievement of comparable sensitivity and specificity. Four subgroups were identified in the patients with PRWP: Group I - anterior myocardial infarction (AMI) (20/56, 35%); Group II - left ventricular hypertrophy (LVH) (8/56, 14%); Group III - right ventricular hypertrophy (RVH) (7/56, 13%); AND Group IV - leftward axis (LA) (21/56, 38%). The best discriminator for vectorcardiogram (VCG) AMI was RV3 less than or equal to 1.5mm or R1 less than or equal to 4.0mm (18/20, 90% sensitivity; 26/36, 72% specificity). RVH and LVH were identified by R1 less than or equal to 4.0mm and S1 greater than or equal to 1.0mm and standard LVH voltage criteria respectively. Group IV patients (PRWP without VCG criteria for AMI, LVH or RVH) were identified by exclusion. \"Reversed R wave progression\" (RRWP) was more specific for AMI than was simple PRWP. The same discriminators, however, were applicable. It is clinically useful to note that 72% (26/36) of patients with either PRWP or RRWP who did not exhibit VCG AMI could be identified by 12 lead ECG with only 2/28 (7%) VCG false negative AMI."} {"id": "PMID:154546", "title": "Validity of psychotraumatic reactions.", "content": "To determine whether posttraumatic reactions occurred in injured individuals not confronted with litigation or compensation (as reckoned in the U.S.), a parallel study was undertaken in a social-democratic country (Austria) between ski- and work-injured groups. Although each group had a significantly different way of regarding the injury, there appeared to be a comparable incidence of posttraumatic psychiatric reaction in each. The absence of compensation (in contrast to disability maintenance) did not inhibit the appearance of the posttraumatic reaction. A discussion of the effects of compensation and litigation pointed out the separate nature of the problems associated with these two aspects of dealing with injury, with those problems being imposed upon, but not causative of, the posttraumatic psychiatric reaction.", "contents": "Validity of psychotraumatic reactions. To determine whether posttraumatic reactions occurred in injured individuals not confronted with litigation or compensation (as reckoned in the U.S.), a parallel study was undertaken in a social-democratic country (Austria) between ski- and work-injured groups. Although each group had a significantly different way of regarding the injury, there appeared to be a comparable incidence of posttraumatic psychiatric reaction in each. The absence of compensation (in contrast to disability maintenance) did not inhibit the appearance of the posttraumatic reaction. A discussion of the effects of compensation and litigation pointed out the separate nature of the problems associated with these two aspects of dealing with injury, with those problems being imposed upon, but not causative of, the posttraumatic psychiatric reaction."} {"id": "PMID:154545", "title": "Comparison of the genetic activity of 5-nitroimidazole derivatives in Escherichia coli, Neurospora crassa, Saccharomyces cerevisiae and Drosophila melanogaster.", "content": "5-nitroimidazoles, including metronidazole (compound 1) and 3 analogues (compounds 2, 3 and 4) of actual or potential chemotherapeutic use were assayed for genetic activity in test systems detecting forward and back mutations in Escherichia coli K-12/343/113, forward mutations in Neurospora crassa heterokaryon 12, mitotic gene conversion in the heteroallelic diploid yeast strain Saccharomyces cerevisiae D4 and sex-linked recessive lethals in Drosophila melanogaster. Whereas metronidazole exhibits moderate mutagenic activity in E. coli, two of the analogues, compounds 2 and 3 are strongly mutagenic even at concentrations that do not inactive the colony forming ability of the cells. The analogue compound 4 does not show any effect toward E. coli under the present experimental conditions. Similar results were obtained with N. crassa, with S. cerevisiae and with Drosophila in which compound 2 exhibits the highest effect, while compound 4 is non-mutagenic in all assays. These biological effects have been partly explained on the basis of differences in the chemical structure of the compounds.", "contents": "Comparison of the genetic activity of 5-nitroimidazole derivatives in Escherichia coli, Neurospora crassa, Saccharomyces cerevisiae and Drosophila melanogaster. 5-nitroimidazoles, including metronidazole (compound 1) and 3 analogues (compounds 2, 3 and 4) of actual or potential chemotherapeutic use were assayed for genetic activity in test systems detecting forward and back mutations in Escherichia coli K-12/343/113, forward mutations in Neurospora crassa heterokaryon 12, mitotic gene conversion in the heteroallelic diploid yeast strain Saccharomyces cerevisiae D4 and sex-linked recessive lethals in Drosophila melanogaster. Whereas metronidazole exhibits moderate mutagenic activity in E. coli, two of the analogues, compounds 2 and 3 are strongly mutagenic even at concentrations that do not inactive the colony forming ability of the cells. The analogue compound 4 does not show any effect toward E. coli under the present experimental conditions. Similar results were obtained with N. crassa, with S. cerevisiae and with Drosophila in which compound 2 exhibits the highest effect, while compound 4 is non-mutagenic in all assays. These biological effects have been partly explained on the basis of differences in the chemical structure of the compounds."} {"id": "PMID:154557", "title": "Activity patterns in individual hindlimb primary and secondary muscle spindle afferents during normal movements in unrestrained cats.", "content": "1. Chronically implanted microelectrode wires in the L7 and S1 dorsal root ganglia were used to record unit activity from cat hindlimb primary and secondary muscle spindle afferents. Units could be reliably recorded for several days, permitting comparison of their activity with homonymous muscle EMG and length during a variety of normal, unrestrained movements. 2. The general observation was that among both primary and secondary endings there was a broad range of different patterns of activity depending on the type of muscle involved and the type of movement performed. 3. During walking, the activity of a given spindle primary was usually consistent among similar step cycles. However, the activity was usually poorly correlated with absolute muscle length, apparently unrealted to velocity of muscle stretch, and could change markedly for similar movements performed under different conditions. 4. Spindle activity modulation not apparently related to muscle length changes was assumed to be influenced by fusimotor activity. In certain muscles, this presumption leads to the conclusion that gamma-motoneurons may be activated out of phase with homonymous alpha-motoneurons as well as by more conventional alpha-gamma-motoneuron coactivation. 5. Simultaneous recordings of two spindle primary afferents from extensor digitorum longus indicated that spindles within the same muscle may differ considerably with respect to this presumed gamma-motoneuron drive. 6. Spindle secondary endings appeared to be predominantly passive indicators of muscle length during walking, but could demonstrate apparently strong fusimotor modulation during other motor activities such as postural changes and paw shaking. 7. Both primary and secondary endings were observed to undergo very rapid modulation of firing rates in response to presumed reflexly induced intrafusal contractions. 8. It is suggested that the pattern of fusimotor control of spindles may be tailored to the specific muscle and task being performed, rather than necessarily dominated by rigid alpha-gamma coactivation.", "contents": "Activity patterns in individual hindlimb primary and secondary muscle spindle afferents during normal movements in unrestrained cats. 1. Chronically implanted microelectrode wires in the L7 and S1 dorsal root ganglia were used to record unit activity from cat hindlimb primary and secondary muscle spindle afferents. Units could be reliably recorded for several days, permitting comparison of their activity with homonymous muscle EMG and length during a variety of normal, unrestrained movements. 2. The general observation was that among both primary and secondary endings there was a broad range of different patterns of activity depending on the type of muscle involved and the type of movement performed. 3. During walking, the activity of a given spindle primary was usually consistent among similar step cycles. However, the activity was usually poorly correlated with absolute muscle length, apparently unrealted to velocity of muscle stretch, and could change markedly for similar movements performed under different conditions. 4. Spindle activity modulation not apparently related to muscle length changes was assumed to be influenced by fusimotor activity. In certain muscles, this presumption leads to the conclusion that gamma-motoneurons may be activated out of phase with homonymous alpha-motoneurons as well as by more conventional alpha-gamma-motoneuron coactivation. 5. Simultaneous recordings of two spindle primary afferents from extensor digitorum longus indicated that spindles within the same muscle may differ considerably with respect to this presumed gamma-motoneuron drive. 6. Spindle secondary endings appeared to be predominantly passive indicators of muscle length during walking, but could demonstrate apparently strong fusimotor modulation during other motor activities such as postural changes and paw shaking. 7. Both primary and secondary endings were observed to undergo very rapid modulation of firing rates in response to presumed reflexly induced intrafusal contractions. 8. It is suggested that the pattern of fusimotor control of spindles may be tailored to the specific muscle and task being performed, rather than necessarily dominated by rigid alpha-gamma coactivation."} {"id": "PMID:154558", "title": "Physiological properties of muscle spindles in dorsal neck muscles of the cat.", "content": "1. Single-fiber recording was used to examine the properties of 107 spindle endings in cat biventer cervicis (BC) and complexus (CM) muscles. Responses of receptors were examined following muscle contraction and ramp and hold stretch. Twenty-two endings in splenius (SP) were also examined, but their responses could not be quantitated because the anatomy of SP prevented the application of appropriate stretches. 2. Conduction velocitites of spindle afferents ranged from 13 to 90 m/s. Endings with primary response patterns usually had faster conduction velocities than secondary endings, but there was overlap in the conduction velocity ranges of the two subgroups. 3. Most neck spindle afferents could be classified as either primary or secondary by a constellation of physiological criteria including dynamic response pattern, dynamic index, and variability of resting discharge frequency. However, 22 of 107 endings from BC and CM had responses with characteristics intermediate between primary and secondary responses. The possible sources of these characteristics are discussed. 4. Despite the similarity in properties between spindles of different neck muscles, the length sensitivities of CM spindles were high compared to those of BC spindles. CM spindles showed length-related modulation of firing frequency over a more restricted range of initial muscle lengths than did BC spindles. 5. Eight Golgi tendon organs (GTO) were identified by their characteristics responses. Conduction velocities obtained for five GTO afferent nerves ranged from 50 to 67 m/s. Recordings were also made from receptros in deep muscles surrounding the vertebrae. These receptors had properties characteristic of muscle spindles.", "contents": "Physiological properties of muscle spindles in dorsal neck muscles of the cat. 1. Single-fiber recording was used to examine the properties of 107 spindle endings in cat biventer cervicis (BC) and complexus (CM) muscles. Responses of receptors were examined following muscle contraction and ramp and hold stretch. Twenty-two endings in splenius (SP) were also examined, but their responses could not be quantitated because the anatomy of SP prevented the application of appropriate stretches. 2. Conduction velocitites of spindle afferents ranged from 13 to 90 m/s. Endings with primary response patterns usually had faster conduction velocities than secondary endings, but there was overlap in the conduction velocity ranges of the two subgroups. 3. Most neck spindle afferents could be classified as either primary or secondary by a constellation of physiological criteria including dynamic response pattern, dynamic index, and variability of resting discharge frequency. However, 22 of 107 endings from BC and CM had responses with characteristics intermediate between primary and secondary responses. The possible sources of these characteristics are discussed. 4. Despite the similarity in properties between spindles of different neck muscles, the length sensitivities of CM spindles were high compared to those of BC spindles. CM spindles showed length-related modulation of firing frequency over a more restricted range of initial muscle lengths than did BC spindles. 5. Eight Golgi tendon organs (GTO) were identified by their characteristics responses. Conduction velocities obtained for five GTO afferent nerves ranged from 50 to 67 m/s. Recordings were also made from receptros in deep muscles surrounding the vertebrae. These receptors had properties characteristic of muscle spindles."} {"id": "PMID:154561", "title": "Perceptions of an aggressive encounter as a function of the victim's salience and the perceiver's arousal.", "content": "Two studies were conducted to investigate the effects of a victim's physical salience and perceivers' arousal on perceptions of a verbally aggressive interaction. Based upon evidence that there is a tendency to attribute causality to salient stimulus persons and to form more evaluatively extreme impressions of such persons, it was predicted that an aggressor's behavior would be attributed more to causes in a physically salient than a nonsalient victim and that the behavior of a salient victim would be evaluated more extremely than that of a nonsalient victim. Based upon Easterbrook's hypothesis that arousal narrows the focus of attention to the most salient cues in the situation, it was further predicted that aroused perceivers would manifest both a stronger tendency to attribute causality to a physically salient victim of aggression and more extreme ratings of the stimulus persons than would nonaroused perceivers. The results supported all of the experimental hypotheses except one: The tendency to attribute the aggressor's behavior more to a physically salient than a nonsalient victim was not greater for aroused than for nonaroused perceivers.", "contents": "Perceptions of an aggressive encounter as a function of the victim's salience and the perceiver's arousal. Two studies were conducted to investigate the effects of a victim's physical salience and perceivers' arousal on perceptions of a verbally aggressive interaction. Based upon evidence that there is a tendency to attribute causality to salient stimulus persons and to form more evaluatively extreme impressions of such persons, it was predicted that an aggressor's behavior would be attributed more to causes in a physically salient than a nonsalient victim and that the behavior of a salient victim would be evaluated more extremely than that of a nonsalient victim. Based upon Easterbrook's hypothesis that arousal narrows the focus of attention to the most salient cues in the situation, it was further predicted that aroused perceivers would manifest both a stronger tendency to attribute causality to a physically salient victim of aggression and more extreme ratings of the stimulus persons than would nonaroused perceivers. The results supported all of the experimental hypotheses except one: The tendency to attribute the aggressor's behavior more to a physically salient than a nonsalient victim was not greater for aroused than for nonaroused perceivers."} {"id": "PMID:154562", "title": "Recruitment order of human spindle endings in isometric voluntary contractions.", "content": "1. The responses of twenty-two spindle endings in the anterior tibial and toe extensor muscles of human subjects were studied during isometric voluntary contractions of the receptor-bearing muscle with the ankle joint fixed in 25 degrees plantar flexion.2. The discharge of eighteen endings accelerated in voluntary contractions when the contraction strength exceeded a threshold level which differed for different endings but was reproducible for the same ending.3. With contractions of slow onset the latency to spindle acceleration varied with the speed of onset of the contraction. Endings with a background discharge were often unloaded by contractions until the contraction strength exceeded the threshold for activation of the ending.4. No correlation was found between the sensitivity of a spindle to external length changes and its ease of activation in a voluntary contraction. For two spindle endings with a background discharge there was no change in either discharge frequency or the regularity of spindle discharge during contractions which were below the threshold for activation of the endings. It is concluded that the threshold for activation of a spindle ending in an isometric voluntary contraction is determined by its fusimotor innervation, and that fusimotor neurones probably have a recruitment order, much as do skeletomotor neurones.5. Once activated, the discharge of spindle endings fluctuated with changes in skeletomotor activity but the relationship for some endings contained non-linearities. Such non-linearities were not as apparent in multi-unit recordings from a number of spindle endings in the contracting muscle. It is concluded that the fusimotor drive to a muscle is proportional to the skeletomotor drive to the muscle, and that skeletomotor and fusimotor neurones are subjected to similar if not identical descending command signals. From the work of Evarts (1968), it seems likely that these command signals are related more to desired muscle force than to desired muscle length.", "contents": "Recruitment order of human spindle endings in isometric voluntary contractions. 1. The responses of twenty-two spindle endings in the anterior tibial and toe extensor muscles of human subjects were studied during isometric voluntary contractions of the receptor-bearing muscle with the ankle joint fixed in 25 degrees plantar flexion.2. The discharge of eighteen endings accelerated in voluntary contractions when the contraction strength exceeded a threshold level which differed for different endings but was reproducible for the same ending.3. With contractions of slow onset the latency to spindle acceleration varied with the speed of onset of the contraction. Endings with a background discharge were often unloaded by contractions until the contraction strength exceeded the threshold for activation of the ending.4. No correlation was found between the sensitivity of a spindle to external length changes and its ease of activation in a voluntary contraction. For two spindle endings with a background discharge there was no change in either discharge frequency or the regularity of spindle discharge during contractions which were below the threshold for activation of the endings. It is concluded that the threshold for activation of a spindle ending in an isometric voluntary contraction is determined by its fusimotor innervation, and that fusimotor neurones probably have a recruitment order, much as do skeletomotor neurones.5. Once activated, the discharge of spindle endings fluctuated with changes in skeletomotor activity but the relationship for some endings contained non-linearities. Such non-linearities were not as apparent in multi-unit recordings from a number of spindle endings in the contracting muscle. It is concluded that the fusimotor drive to a muscle is proportional to the skeletomotor drive to the muscle, and that skeletomotor and fusimotor neurones are subjected to similar if not identical descending command signals. From the work of Evarts (1968), it seems likely that these command signals are related more to desired muscle force than to desired muscle length."} {"id": "PMID:154563", "title": "Mechanism of the vibration paradox: excitatory and inhibitory effects of tendon vibration on single soleus muscle motor units in man.", "content": "1. The parameters of presynaptic inhibition of the Ia spindle afferents from soleus muscle by vibration have been investigated. The inhibitory effects increase with the amplitude of vibration, but decrease when the vibration frequency is increased.2. The monosynaptic reflex threshold of twenty-one single soleus motor units activated in the H (Hoffmann) reflex by a single electrical stimulus to the posterior tibial nerve was estimated quantitatively and expressed in relation to the size of the simultaneously recorded H reflex.3. A parametric study of the effects of various Achilles tendon vibrations on the reflex threshold of the single soleus motor units indicated that their order of derecruitment is concordant with their rank order for activation in the phasic reflexes of the soleus. The last recruited motoneurones are the most susceptible to being silenced by steady vibration.4. Muscle vibration progressively recruits single motor units according to the motoneurone size principle through polysynaptic proprioceptive pathways. However the presynaptic inhibition of Ia spindle afferents simultaneously induced by the vibration works in reverse on the same rank order of motoneurones of the soleus spinal pool, thereby limiting the polysynaptic recruitment of units in the tonic vibration reflex while depressing the autogenic phasic proprioceptive reflexes. These mechanisms elucidate the so-called vibration paradox and extend the size principle of Henneman to presynaptic inhibitory effects.", "contents": "Mechanism of the vibration paradox: excitatory and inhibitory effects of tendon vibration on single soleus muscle motor units in man. 1. The parameters of presynaptic inhibition of the Ia spindle afferents from soleus muscle by vibration have been investigated. The inhibitory effects increase with the amplitude of vibration, but decrease when the vibration frequency is increased.2. The monosynaptic reflex threshold of twenty-one single soleus motor units activated in the H (Hoffmann) reflex by a single electrical stimulus to the posterior tibial nerve was estimated quantitatively and expressed in relation to the size of the simultaneously recorded H reflex.3. A parametric study of the effects of various Achilles tendon vibrations on the reflex threshold of the single soleus motor units indicated that their order of derecruitment is concordant with their rank order for activation in the phasic reflexes of the soleus. The last recruited motoneurones are the most susceptible to being silenced by steady vibration.4. Muscle vibration progressively recruits single motor units according to the motoneurone size principle through polysynaptic proprioceptive pathways. However the presynaptic inhibition of Ia spindle afferents simultaneously induced by the vibration works in reverse on the same rank order of motoneurones of the soleus spinal pool, thereby limiting the polysynaptic recruitment of units in the tonic vibration reflex while depressing the autogenic phasic proprioceptive reflexes. These mechanisms elucidate the so-called vibration paradox and extend the size principle of Henneman to presynaptic inhibitory effects."} {"id": "PMID:154568", "title": "A survey of preceived oral health needs of homebound patients.", "content": "1. While almost 60 percent of all patients reported dental needs, it is assumed that actual needs were in fact considerably higher. Problems relating to dentures were the most freqeuntly expressed complaint. 2. A strong relation existed between the ability of homebound patients to get to a dentist and the time elapsed since last dental visit. Number of teeth was a significant determinant in frequency of seeking care. Persons with teeth or dentures sought treatment more often than those who were edentulous. Pain was the only variable for which a difference was noted between the two groups in the effect on time of last dental visit. 3. The study revealed an inaccessibility of dental care for the majority of patients confined to their homes. Ability to get to the dentist was identified as a major barrier to care for the homebound. The delivery of dental services to such patients in their immediate surroundings, by specially trained dental professionals using mobile units, must therefore be seriously considered as a means for improving access to care for this population.", "contents": "A survey of preceived oral health needs of homebound patients. 1. While almost 60 percent of all patients reported dental needs, it is assumed that actual needs were in fact considerably higher. Problems relating to dentures were the most freqeuntly expressed complaint. 2. A strong relation existed between the ability of homebound patients to get to a dentist and the time elapsed since last dental visit. Number of teeth was a significant determinant in frequency of seeking care. Persons with teeth or dentures sought treatment more often than those who were edentulous. Pain was the only variable for which a difference was noted between the two groups in the effect on time of last dental visit. 3. The study revealed an inaccessibility of dental care for the majority of patients confined to their homes. Ability to get to the dentist was identified as a major barrier to care for the homebound. The delivery of dental services to such patients in their immediate surroundings, by specially trained dental professionals using mobile units, must therefore be seriously considered as a means for improving access to care for this population."} {"id": "PMID:154569", "title": "Sciatic nerve injury in a patient undergoing laparoscopy.", "content": "A case of injury to the sciatic nerve at the time of laparoscopy is presented. The problem can generally be prevented, and the resolution, although lengthy, ususally is complete.", "contents": "Sciatic nerve injury in a patient undergoing laparoscopy. A case of injury to the sciatic nerve at the time of laparoscopy is presented. The problem can generally be prevented, and the resolution, although lengthy, ususally is complete."} {"id": "PMID:154570", "title": "Elimination of contamination without caesarian derivation--success or failure?", "content": "Unfortunately, only successes tend to be published, so we are denied knowledge of partial successes and failures regarding SPF unit breakdowns. If more workers were prepared to be open about their partial successes, a combination of various techniques are appropriate to the case, could prove to be most successful. Each SPF colony is different and must be considered on its merits, nature of contamination, species and strains of animals and so on, but it would seem that caesarian derivation is not now always the only course of action.", "contents": "Elimination of contamination without caesarian derivation--success or failure? Unfortunately, only successes tend to be published, so we are denied knowledge of partial successes and failures regarding SPF unit breakdowns. If more workers were prepared to be open about their partial successes, a combination of various techniques are appropriate to the case, could prove to be most successful. Each SPF colony is different and must be considered on its merits, nature of contamination, species and strains of animals and so on, but it would seem that caesarian derivation is not now always the only course of action."} {"id": "PMID:154572", "title": "Twelve years experience in establishing larger colonies of small laboratory animals under SPF conditions by means of germfree technology.", "content": "The special procedures and techniques to develop poly-associated gnotobiotic animals in order to start large SPF colonies of small laboratory animals are discussed.", "contents": "Twelve years experience in establishing larger colonies of small laboratory animals under SPF conditions by means of germfree technology. The special procedures and techniques to develop poly-associated gnotobiotic animals in order to start large SPF colonies of small laboratory animals are discussed."} {"id": "PMID:154573", "title": "The effect of germfree and SPF maintenance conditions on the lifespan and diseases of small laboratory animals.", "content": "The mortality rates and spontaneous diseases defining the course of natural mortality graphs in colonies of Han: NMRI mice kept under conventional, SPF and germfree maintenance conditions are reported. A specific problem in SPF colonies is caused by ubiquitous germs. The lesions and possible reasons for such types of infections are discussed.", "contents": "The effect of germfree and SPF maintenance conditions on the lifespan and diseases of small laboratory animals. The mortality rates and spontaneous diseases defining the course of natural mortality graphs in colonies of Han: NMRI mice kept under conventional, SPF and germfree maintenance conditions are reported. A specific problem in SPF colonies is caused by ubiquitous germs. The lesions and possible reasons for such types of infections are discussed."} {"id": "PMID:154574", "title": "The breeding and use of specific pathogen-free (SPF) rats.", "content": "Bronchiectasis is common in older rats and is a serious complication when the lungs are repuired for research purposes. SPF rats do not develop this complication, but special isolated accommodation must be provided and care of the animals must avoid introduction of outside micro-organisms. Animals removed from the isolated accommodation for experimental work are not returned, but can be kept in the general animal house provided there are no conventionally-bred rats.", "contents": "The breeding and use of specific pathogen-free (SPF) rats. Bronchiectasis is common in older rats and is a serious complication when the lungs are repuired for research purposes. SPF rats do not develop this complication, but special isolated accommodation must be provided and care of the animals must avoid introduction of outside micro-organisms. Animals removed from the isolated accommodation for experimental work are not returned, but can be kept in the general animal house provided there are no conventionally-bred rats."} {"id": "PMID:154577", "title": "Dementia in ageing mental defectives: a clinical and neuropathological study.", "content": "A follow-up clinical and neuropathological study of eleven mentally subnormal subjects diagnosed in life as suffering from either senile, cerebral arteriosclerotic or pre-senile dementia is reported. Of the original cohort seven have died and neuropathological examination has confirmed the diagnosis of cerebral arterisclerotic dementia in three, senile dementia in one and senile dementia of unusually early onset in another mongol patient. Autopsy was refused in one patient and in the other patient neuropathological examination revealed a diffuse sclerosis of Pelizaeus-Merzbacher type. In the four survivors the clinical diagnosis of dementia would appear to be probably correct in one patient, partially correct in another, and wrong in two patients. The study has confirmed that dementia can be diagnosed in mental defectives with a reasonable degree of accuracy and draws attention to the potential interest of neuropathological examinations in decreased psychiatrically disordered mentally subnormal subjects.", "contents": "Dementia in ageing mental defectives: a clinical and neuropathological study. A follow-up clinical and neuropathological study of eleven mentally subnormal subjects diagnosed in life as suffering from either senile, cerebral arteriosclerotic or pre-senile dementia is reported. Of the original cohort seven have died and neuropathological examination has confirmed the diagnosis of cerebral arterisclerotic dementia in three, senile dementia in one and senile dementia of unusually early onset in another mongol patient. Autopsy was refused in one patient and in the other patient neuropathological examination revealed a diffuse sclerosis of Pelizaeus-Merzbacher type. In the four survivors the clinical diagnosis of dementia would appear to be probably correct in one patient, partially correct in another, and wrong in two patients. The study has confirmed that dementia can be diagnosed in mental defectives with a reasonable degree of accuracy and draws attention to the potential interest of neuropathological examinations in decreased psychiatrically disordered mentally subnormal subjects."} {"id": "PMID:154578", "title": "Pituitary function in Down's syndrome.", "content": "Pituitary function studies have been carried out in eight male and eight female patients with Down's syndrome who were suspected of having hypothyroidism secondary to pituitary deficiency. In all cases, the response of Human Growth Hormone to hypoglycaemia was adequate and the response of Lutenising Hormone and Follicle Stimulating Hormone to the injection of Lutenising Hormone and Follicle Stimulating Hormone was not signfiicantly greater than that in age and sex-matched institutionalised controls. Therefore there is no evidence that the relative hypothyroidism in these patients is due to pituitary hypofunction, nor do the results provide evidence of pituitary deficiency in Down's syndrome generally.", "contents": "Pituitary function in Down's syndrome. Pituitary function studies have been carried out in eight male and eight female patients with Down's syndrome who were suspected of having hypothyroidism secondary to pituitary deficiency. In all cases, the response of Human Growth Hormone to hypoglycaemia was adequate and the response of Lutenising Hormone and Follicle Stimulating Hormone to the injection of Lutenising Hormone and Follicle Stimulating Hormone was not signfiicantly greater than that in age and sex-matched institutionalised controls. Therefore there is no evidence that the relative hypothyroidism in these patients is due to pituitary hypofunction, nor do the results provide evidence of pituitary deficiency in Down's syndrome generally."} {"id": "PMID:154581", "title": "The chemoarchitectonics of the diencephalon of frog (Rana tigrina).", "content": "The study deals with the distribution of acid and alkaline phosphatases, ATPase, 5-nucleotidase, nonspecific esterase, specific cholinesterase, and beta-galactosidase in the diencephalon of the frog. The highlights of the present study are the following: i) Acid phosphatase is present in all the neurons, whereas the tracts and commissures are completely negative. ii) Most of the tracts and commissures are positive for 5-nucleotidase. This confirms the author's previous findings that the tracts and commissures of all the areas of frog brain are intensely positive for 5-nucleotidase. iii) beta-galactosidase activity in the nuclei of the diencephalon is either mild or completely absent, whereas the commissures and tracts show positive activity. iv) Habenulothalamic connections are intensely positive for specific cholinesterase and non-specific esterase, moderately positive for beta-galactosidase and completely negative for other enzymes. v) The epiphysis (pineal organ) shows intense reaction for adenosine triphosphatase, acid phosphatase, and 5-nucleotidase and moderate reaction for alkaline phosphatase and non-specific esterase. In contrast to the above enzymes, the specific cholinesterase and beta-galactosidase are completely missing. vi) Lateral forebrain bundles are completely negative for all the enzymes except alkaline phosphatase and beta-galactosidase. The distribution of these enzymes has been correlated with the functional aspects of various nuclei, tracts, and commissures of the diencephalon of the frog.", "contents": "The chemoarchitectonics of the diencephalon of frog (Rana tigrina). The study deals with the distribution of acid and alkaline phosphatases, ATPase, 5-nucleotidase, nonspecific esterase, specific cholinesterase, and beta-galactosidase in the diencephalon of the frog. The highlights of the present study are the following: i) Acid phosphatase is present in all the neurons, whereas the tracts and commissures are completely negative. ii) Most of the tracts and commissures are positive for 5-nucleotidase. This confirms the author's previous findings that the tracts and commissures of all the areas of frog brain are intensely positive for 5-nucleotidase. iii) beta-galactosidase activity in the nuclei of the diencephalon is either mild or completely absent, whereas the commissures and tracts show positive activity. iv) Habenulothalamic connections are intensely positive for specific cholinesterase and non-specific esterase, moderately positive for beta-galactosidase and completely negative for other enzymes. v) The epiphysis (pineal organ) shows intense reaction for adenosine triphosphatase, acid phosphatase, and 5-nucleotidase and moderate reaction for alkaline phosphatase and non-specific esterase. In contrast to the above enzymes, the specific cholinesterase and beta-galactosidase are completely missing. vi) Lateral forebrain bundles are completely negative for all the enzymes except alkaline phosphatase and beta-galactosidase. The distribution of these enzymes has been correlated with the functional aspects of various nuclei, tracts, and commissures of the diencephalon of the frog."} {"id": "PMID:154582", "title": "Doppler flowmeter in the differential diagnosis of the acute scrotum in children.", "content": "A Doppler flowmeter was used to evaluate an acute scrotum in 23 children. A diminished or absent flow was noted in cases of torsion of the testis. Orchitis, epididymitis and torsion of the testicular appendix were accompanied with an increased blood flow. Inflammatory and ischemic lesions could be detected and in all operated cases the diagnosis proved to be correct. Unnecessary operations in cases of torsion of the testicular appendix can be avoided with this accurate non-invasive method.", "contents": "Doppler flowmeter in the differential diagnosis of the acute scrotum in children. A Doppler flowmeter was used to evaluate an acute scrotum in 23 children. A diminished or absent flow was noted in cases of torsion of the testis. Orchitis, epididymitis and torsion of the testicular appendix were accompanied with an increased blood flow. Inflammatory and ischemic lesions could be detected and in all operated cases the diagnosis proved to be correct. Unnecessary operations in cases of torsion of the testicular appendix can be avoided with this accurate non-invasive method."} {"id": "PMID:154583", "title": "[Results of application of CS-1170 to pediatric infections (author's transl)].", "content": "CS-1170 was administered in a total of 11 cases including respiratory infections, urinary-tract infections, and subacute bacterial endocarditis. It was effective in all of the cases; markedly effective in a case of bronchopneumonia with underlying Down's syndrome and infantile spasm and in 2 cases of urinary-tract infections with E. coli. The fact that it was effective for urinary-tract infection with E. coli which showed no sensitivity to ampicillin or cefazolin demonstrates the clinical significance and usefulness of CS-1170 which is said to have a strong antibacterial activity for bacterial producing beta-lactamase. No side effect was observed.", "contents": "[Results of application of CS-1170 to pediatric infections (author's transl)]. CS-1170 was administered in a total of 11 cases including respiratory infections, urinary-tract infections, and subacute bacterial endocarditis. It was effective in all of the cases; markedly effective in a case of bronchopneumonia with underlying Down's syndrome and infantile spasm and in 2 cases of urinary-tract infections with E. coli. The fact that it was effective for urinary-tract infection with E. coli which showed no sensitivity to ampicillin or cefazolin demonstrates the clinical significance and usefulness of CS-1170 which is said to have a strong antibacterial activity for bacterial producing beta-lactamase. No side effect was observed."} {"id": "PMID:154598", "title": "Congenital aortic valve anomaly. Aortic regurgitation with left coronary artery isolation.", "content": "A case is reported of aortic regurgitation resulting from a congenitally abnormal aortic valve. The left coronary cusp of the valve was small and adhered to the aortic wall, so that there was insufficient valve tissue to maintain diastolic valve competence. In addition, this rudimentary cusp completely occluded the left coronary ostium. The patient was treated successfully by valve replacement.", "contents": "Congenital aortic valve anomaly. Aortic regurgitation with left coronary artery isolation. A case is reported of aortic regurgitation resulting from a congenitally abnormal aortic valve. The left coronary cusp of the valve was small and adhered to the aortic wall, so that there was insufficient valve tissue to maintain diastolic valve competence. In addition, this rudimentary cusp completely occluded the left coronary ostium. The patient was treated successfully by valve replacement."} {"id": "PMID:154599", "title": "Caplike double-horned double-outlet right ventricle. Report of two cases.", "content": "Two patients with a rare form of double-chambered, double-outlet right ventricle (DORV) are described. Both patients had associated pulmonary stenosis, ventricular septal defect, and a large tricuspid valve whose chordal attachments crossed the right ventricular outflow tract. The angiocardiographic, echocardiographic, and operative findings were distinctive. The right ventricle was positioned as a \"cap\" sitting atop the ventricular septal defect at the cephalad end of the left ventricle. The right ventricle, with its two \"horns,\" was likened to a rider straddling a saddle. Tricuspid chordal attachments extended into each of the two right ventricular \"horn.\" No repair was performed in the asymptomatic patient. The other repair involved closure of the tricuspid orifice and insertion of a valved extracardiac conduit from the right atrium to the pulmonary artery.", "contents": "Caplike double-horned double-outlet right ventricle. Report of two cases. Two patients with a rare form of double-chambered, double-outlet right ventricle (DORV) are described. Both patients had associated pulmonary stenosis, ventricular septal defect, and a large tricuspid valve whose chordal attachments crossed the right ventricular outflow tract. The angiocardiographic, echocardiographic, and operative findings were distinctive. The right ventricle was positioned as a \"cap\" sitting atop the ventricular septal defect at the cephalad end of the left ventricle. The right ventricle, with its two \"horns,\" was likened to a rider straddling a saddle. Tricuspid chordal attachments extended into each of the two right ventricular \"horn.\" No repair was performed in the asymptomatic patient. The other repair involved closure of the tricuspid orifice and insertion of a valved extracardiac conduit from the right atrium to the pulmonary artery."} {"id": "PMID:154604", "title": "[Occupational dermatoses in workers of a building combine].", "content": "Examinations involved 33 building combine workers. Findings were as follows: occupational acne in 94% of workers, toxic dermatitis of epidermis and skin in 42% and allergic dermatitis of epidermis and skin in 9% of workers, resulting from work in exposure to cement, lime and oils.", "contents": "[Occupational dermatoses in workers of a building combine]. Examinations involved 33 building combine workers. Findings were as follows: occupational acne in 94% of workers, toxic dermatitis of epidermis and skin in 42% and allergic dermatitis of epidermis and skin in 9% of workers, resulting from work in exposure to cement, lime and oils."} {"id": "PMID:154605", "title": "[Dermatoses in tapestry workers].", "content": "From among 810 persons subjected to a medical examination, skin lesions were found in 33.3%. These were mostly: seborrhea (89 cases), occupational naevi (55 cases), dermatomycosis (49 cases), urticaria (21 cases), eczema (12 cases). Other dermatoses were found in 44 workers, however, in a small percentage, not greater than in other non-industrial populations. No occupational dermatoses resulting from exposure to fundamental materials or dyes used in production were found.", "contents": "[Dermatoses in tapestry workers]. From among 810 persons subjected to a medical examination, skin lesions were found in 33.3%. These were mostly: seborrhea (89 cases), occupational naevi (55 cases), dermatomycosis (49 cases), urticaria (21 cases), eczema (12 cases). Other dermatoses were found in 44 workers, however, in a small percentage, not greater than in other non-industrial populations. No occupational dermatoses resulting from exposure to fundamental materials or dyes used in production were found."} {"id": "PMID:154608", "title": "[Number of butyric acid bacteria belonging to the genus Clostridium in the slimy sediments of Volga reservoirs].", "content": "The number of Clostridium pasteurianum, Cl. butyricum, and Cl. acetobutylicum was determined in ooze deposits of the Volga River reservoirs using enriched nutrient media. The bacterial number for the two former species was about 1 + 10(6) cells per 1 ml of ooze with a high content of easily assimilated organic substances, thus being by 1--3 orders of magnitude higher than for Cl. pasteurianum on media without nitrogen. The bacterial number for Cl. acetobutylicum was 0.1--1 + 10(3) cells per 1 ml.", "contents": "[Number of butyric acid bacteria belonging to the genus Clostridium in the slimy sediments of Volga reservoirs]. The number of Clostridium pasteurianum, Cl. butyricum, and Cl. acetobutylicum was determined in ooze deposits of the Volga River reservoirs using enriched nutrient media. The bacterial number for the two former species was about 1 + 10(6) cells per 1 ml of ooze with a high content of easily assimilated organic substances, thus being by 1--3 orders of magnitude higher than for Cl. pasteurianum on media without nitrogen. The bacterial number for Cl. acetobutylicum was 0.1--1 + 10(3) cells per 1 ml."} {"id": "PMID:154609", "title": "[Comparative characteristics of the numbers of microorganisms in soils and their basement sedimentary rocks].", "content": "Comparative studies on the quantitative composition of microorganisms in soils and basement sedimentary rocks have shown that the latter are rich in microorganisms. The number of microorganisms in basement grounds changes with time, thus indicating their activity. The qualitative composition is poor. At the same time, the total quantity of microorganisms in basement layers is equal to that in soil. Basement layers contain 10 times more microorganisms than eutrophic water reservoirs and 1000 times more than oligotrophic water reservoirs.", "contents": "[Comparative characteristics of the numbers of microorganisms in soils and their basement sedimentary rocks]. Comparative studies on the quantitative composition of microorganisms in soils and basement sedimentary rocks have shown that the latter are rich in microorganisms. The number of microorganisms in basement grounds changes with time, thus indicating their activity. The qualitative composition is poor. At the same time, the total quantity of microorganisms in basement layers is equal to that in soil. Basement layers contain 10 times more microorganisms than eutrophic water reservoirs and 1000 times more than oligotrophic water reservoirs."} {"id": "PMID:154610", "title": "[Gas chromatographic method of determining the intensity of microbiological oxidation of methane in reservoirs].", "content": "A method of gas chromatography is described for determining the rate of microbial methane oxidation. In the Rybinskoye Reservoir, the rate of methane oxidation in the microaerobic zone of water layers near the bottom over the silted former channel of the Mologa River was found to be 51.1 to 86.2 mcl of CH4 per litre per day at 2--3 degrees C, constituting 8--16% of the original methane content.", "contents": "[Gas chromatographic method of determining the intensity of microbiological oxidation of methane in reservoirs]. A method of gas chromatography is described for determining the rate of microbial methane oxidation. In the Rybinskoye Reservoir, the rate of methane oxidation in the microaerobic zone of water layers near the bottom over the silted former channel of the Mologa River was found to be 51.1 to 86.2 mcl of CH4 per litre per day at 2--3 degrees C, constituting 8--16% of the original methane content."} {"id": "PMID:154611", "title": "[Microbiological oxidation of methane in the stratal waters of the Lower Volgian].", "content": "Methanotrophic bacteria are rather widely distributed in bed waters of oil and gas deposits in the Nizhneye Povolzhye. Their number reaches 250 cells per 1 ml of water. However, bacterial methane oxidation is active only in waters whose redox potential exceeds +250 mV. In a number of cases, microbial methane oxidation is limited by the absence of oxygen from bed waters. If air is added to samples of such water, methane dissolved in the water is oxidized by microorganisms at a high rate (2--451 X 10(-4) cm3 of methane per litre of water per day).", "contents": "[Microbiological oxidation of methane in the stratal waters of the Lower Volgian]. Methanotrophic bacteria are rather widely distributed in bed waters of oil and gas deposits in the Nizhneye Povolzhye. Their number reaches 250 cells per 1 ml of water. However, bacterial methane oxidation is active only in waters whose redox potential exceeds +250 mV. In a number of cases, microbial methane oxidation is limited by the absence of oxygen from bed waters. If air is added to samples of such water, methane dissolved in the water is oxidized by microorganisms at a high rate (2--451 X 10(-4) cm3 of methane per litre of water per day)."} {"id": "PMID:154612", "title": "[Bacterial overgrowth of slides and electron microscopic grids in the surface film of water and ooze deposits].", "content": "Distinct bacterial growth can be discerned in the surface water film on semisubmerged slides in the laboratory conditions. The thickness of growth depends on the content of organic substances in water. The growth is found also in natural brine if the content of salts is 127--230 g per litre. A great variety of aqueous bacteria is seen, by means of electron microscopy, on electron-microscopic nets submerged in the surface water layer. New bacterial forms have been found in natural brine. Many creeping bacteria cover slides at the water-ooze interface.", "contents": "[Bacterial overgrowth of slides and electron microscopic grids in the surface film of water and ooze deposits]. Distinct bacterial growth can be discerned in the surface water film on semisubmerged slides in the laboratory conditions. The thickness of growth depends on the content of organic substances in water. The growth is found also in natural brine if the content of salts is 127--230 g per litre. A great variety of aqueous bacteria is seen, by means of electron microscopy, on electron-microscopic nets submerged in the surface water layer. New bacterial forms have been found in natural brine. Many creeping bacteria cover slides at the water-ooze interface."} {"id": "PMID:154616", "title": "Left ventricular function in terminal uremia. A hemodynamic and echocardiographic study.", "content": "14 patients with advanced uremia had a mean cardiac index (CI) of 4.37 +/- 0.25 liters/min/m2, a mean stroke work index (SWI) of 65.6 +/- 3.7 g/m/m2 and a mean left ventricular filling pressure (LVFP) of 16.3 +/- 2.1 mm Hg. The left ventricular performance was estimated to be normal when CI or SWI changes were correlated with simultaneous variation of the LVFP attained during peritoneal dialysis or afterload reduction. CI was high at a normal LVFP, it decreased at low or high LVFP. Guanidines retention, metabolic acidosis and hypocalcemia did not prevent the maintenance of a high CI or SWI. Out of 32 patients, left ventricular hypertrophy and pericardial effusion, conditions which may affect ventricular distensibility, were present in 25 and in 22 echocardiograms, respectively. We suggest that in uremic subjects, LVFP is primarily influenced by volume loads and by ventricular distensibility modifications.", "contents": "Left ventricular function in terminal uremia. A hemodynamic and echocardiographic study. 14 patients with advanced uremia had a mean cardiac index (CI) of 4.37 +/- 0.25 liters/min/m2, a mean stroke work index (SWI) of 65.6 +/- 3.7 g/m/m2 and a mean left ventricular filling pressure (LVFP) of 16.3 +/- 2.1 mm Hg. The left ventricular performance was estimated to be normal when CI or SWI changes were correlated with simultaneous variation of the LVFP attained during peritoneal dialysis or afterload reduction. CI was high at a normal LVFP, it decreased at low or high LVFP. Guanidines retention, metabolic acidosis and hypocalcemia did not prevent the maintenance of a high CI or SWI. Out of 32 patients, left ventricular hypertrophy and pericardial effusion, conditions which may affect ventricular distensibility, were present in 25 and in 22 echocardiograms, respectively. We suggest that in uremic subjects, LVFP is primarily influenced by volume loads and by ventricular distensibility modifications."} {"id": "PMID:154617", "title": "Long-term results in 35 HLA-identical sibling and 3 HLA-identical parent-child renal allograft recipients.", "content": "35 recipients of a renal allograft from an HLA-identical sibling followed for 3 months to nearly 15 years have had 1- and 5-year allograft survivals of 93 and 76%, respectively, levels comparable to the 90 and 80% reported at 1 and 5 years for identical twins. Although high MLC stimulation was related to graft failure, intermediate degrees of stimulation were not. The most common cause of graft failure was chronic rejection (n=4) and of death, myocardial infarction (n=3). However, overall complications such as aseptic necrosis were distinctly lower than in mismatched recipients. 3 children received an allograft from an HLA-identical parent, possible because of a shared parental haplotype, and all have excellent function from 2 to nearly 9 years after transplantation.", "contents": "Long-term results in 35 HLA-identical sibling and 3 HLA-identical parent-child renal allograft recipients. 35 recipients of a renal allograft from an HLA-identical sibling followed for 3 months to nearly 15 years have had 1- and 5-year allograft survivals of 93 and 76%, respectively, levels comparable to the 90 and 80% reported at 1 and 5 years for identical twins. Although high MLC stimulation was related to graft failure, intermediate degrees of stimulation were not. The most common cause of graft failure was chronic rejection (n=4) and of death, myocardial infarction (n=3). However, overall complications such as aseptic necrosis were distinctly lower than in mismatched recipients. 3 children received an allograft from an HLA-identical parent, possible because of a shared parental haplotype, and all have excellent function from 2 to nearly 9 years after transplantation."} {"id": "PMID:154624", "title": "Treatment of Huntington disease with a cholinergic agonist.", "content": "The involuntary movements of Huntington disease may be related to cholinergic hypofunction in the striatum. For this reason, the effect of a direct cholinergic agonist, arecoline, was studied in six patients with this disorder. Rather than improving the chorea, arecoline tended to exacerbate the choreic movements. Arecoline did produce significant alterations of blood pressure, heart rate, and body temperature, probably by central cholinergic stimulation.", "contents": "Treatment of Huntington disease with a cholinergic agonist. The involuntary movements of Huntington disease may be related to cholinergic hypofunction in the striatum. For this reason, the effect of a direct cholinergic agonist, arecoline, was studied in six patients with this disorder. Rather than improving the chorea, arecoline tended to exacerbate the choreic movements. Arecoline did produce significant alterations of blood pressure, heart rate, and body temperature, probably by central cholinergic stimulation."} {"id": "PMID:154627", "title": "Acute myopathy with selective lysis of myosin filaments.", "content": "An acute reversible myopathy characterized by extensive lysis of myosin occurred in a patient who suffered from severe shock, hypoxia, and acidosis. This new clinical pathologic entity illustrates an unusual structural change in muscle associated with these catastrophic clinical circumstances.", "contents": "Acute myopathy with selective lysis of myosin filaments. An acute reversible myopathy characterized by extensive lysis of myosin occurred in a patient who suffered from severe shock, hypoxia, and acidosis. This new clinical pathologic entity illustrates an unusual structural change in muscle associated with these catastrophic clinical circumstances."} {"id": "PMID:154637", "title": "Experimental evaluation of a posterior chamber lens fixated with Dacron.", "content": "A posterior chamber intraocular lens using Dacron fibers to achieve fixation to the iris was studied. The lens was inserted in rabbit eyes following extracapsular lensectomy, and in primate eyes after lensectomy, vitrectomy, and peripheral iridectomy. Surgical implantation of the lenses was simple and quick, and no operative complications occurred. Clinically, no difference was noted in the amount of inflammation in eyes receiving a lens with or without Dacron. None of the lenses implanted in primate eyes dislocated; one placed in a rabbit eye dislocated anteriorly. Postmortem examination demonstrated firm Dacron adherence to iris tissue in all but the one eye with a dislocated lens.", "contents": "Experimental evaluation of a posterior chamber lens fixated with Dacron. A posterior chamber intraocular lens using Dacron fibers to achieve fixation to the iris was studied. The lens was inserted in rabbit eyes following extracapsular lensectomy, and in primate eyes after lensectomy, vitrectomy, and peripheral iridectomy. Surgical implantation of the lenses was simple and quick, and no operative complications occurred. Clinically, no difference was noted in the amount of inflammation in eyes receiving a lens with or without Dacron. None of the lenses implanted in primate eyes dislocated; one placed in a rabbit eye dislocated anteriorly. Postmortem examination demonstrated firm Dacron adherence to iris tissue in all but the one eye with a dislocated lens."} {"id": "PMID:154638", "title": "Iris tissue reaction to dacron and silk in primates: evaluation for intraocular lens fixation.", "content": "Dacron, silk, and a combination of the two were evaluated for tissue ingrowth response in the primate iris with a view towards the feasibility of using these materials for intraocular lens fixation. The materials were well tolerated by all eyes, with no inflammation after seven days and no cases of endophthalmitis occurring. Adherence to iris was strong in silk-containing materials at 14 days by gross and histologic examination, and the Dacron-silk combination was judged most suitable for potential human use.", "contents": "Iris tissue reaction to dacron and silk in primates: evaluation for intraocular lens fixation. Dacron, silk, and a combination of the two were evaluated for tissue ingrowth response in the primate iris with a view towards the feasibility of using these materials for intraocular lens fixation. The materials were well tolerated by all eyes, with no inflammation after seven days and no cases of endophthalmitis occurring. Adherence to iris was strong in silk-containing materials at 14 days by gross and histologic examination, and the Dacron-silk combination was judged most suitable for potential human use."} {"id": "PMID:154639", "title": "Antibody formation to dog pulp tissue altered by Grossman's Formula Sealer via the root canal.", "content": "Pulp tissue from experimental dogs was tested for its antigenicity before and after incubation with Grossman's Formula Sealer (GS). Reactions to Arthus skin tests showed an increased response to pulp that had been incubated in GS, washed, and then injected, as compared with the material alone. Hemagglutinating antibody titers (1:160 to 1:360) were obtained from pulp tissue altered by GS. Inhibition tests showed the specificity of the antibody to be at a dilution titer of 1:200. Therefore, GS altered dog pulp tissue and rendered it antigenically active, and a specific humoral response was produced.", "contents": "Antibody formation to dog pulp tissue altered by Grossman's Formula Sealer via the root canal. Pulp tissue from experimental dogs was tested for its antigenicity before and after incubation with Grossman's Formula Sealer (GS). Reactions to Arthus skin tests showed an increased response to pulp that had been incubated in GS, washed, and then injected, as compared with the material alone. Hemagglutinating antibody titers (1:160 to 1:360) were obtained from pulp tissue altered by GS. Inhibition tests showed the specificity of the antibody to be at a dilution titer of 1:200. Therefore, GS altered dog pulp tissue and rendered it antigenically active, and a specific humoral response was produced."} {"id": "PMID:154642", "title": "Mixed lymphocyte culture (MLC) inhibition in humans due to anti-Ia like (DRW).", "content": "The authors studied the MLC blocking effect of anti-DRW anti-sera. These sera were harvested from multiparous women and their anti-DRW activities were defined (after exhaustive platelets absorption) on a panel of 73 B-lymphocytes. All the six tested sera were strongly inhibitor until dilution greater than 1/500 when they were present in the MLC for all the culture period but without specificity for their relevant target cell. The MLC inhibitory activity was still found in IgG fraction. A significant specific inhibition could be found only when the cultured cells were independently preincubated with the corresponding anti-DRW serum prior culture. In this last case inhibition occured when the target cell (bearing the DRW antigen recognized by the studied sera) was used as the stimulator cell in MLC. A decrease of the inhibition was found when the anti-DRW was absorbed with its relevant target cell but also with non-target cell, as assessed by B-cell cytotoxicity, suggesting that non cytotoxic antibodies directed against \"public\" determinant are involved in MLC inhibition.", "contents": "Mixed lymphocyte culture (MLC) inhibition in humans due to anti-Ia like (DRW). The authors studied the MLC blocking effect of anti-DRW anti-sera. These sera were harvested from multiparous women and their anti-DRW activities were defined (after exhaustive platelets absorption) on a panel of 73 B-lymphocytes. All the six tested sera were strongly inhibitor until dilution greater than 1/500 when they were present in the MLC for all the culture period but without specificity for their relevant target cell. The MLC inhibitory activity was still found in IgG fraction. A significant specific inhibition could be found only when the cultured cells were independently preincubated with the corresponding anti-DRW serum prior culture. In this last case inhibition occured when the target cell (bearing the DRW antigen recognized by the studied sera) was used as the stimulator cell in MLC. A decrease of the inhibition was found when the anti-DRW was absorbed with its relevant target cell but also with non-target cell, as assessed by B-cell cytotoxicity, suggesting that non cytotoxic antibodies directed against \"public\" determinant are involved in MLC inhibition."} {"id": "PMID:154656", "title": "Alkaline deoxyribonucleases released from Neurospora crassa mycelia: two activities not released by mutants with multiple sensitivities to mutagens.", "content": "Three major alkaline deoxyribonuclease (DNase) activities have been identified in sorbose-containing liquid culture medium in which wild-type Neurosporacrassa were grown: DNase A, a Ca++dependent endonuclease of molecular weight 65,000 daltons which has no specificity for single- or double-stranded DNA (ss-DNA or ds-DNA) and no activity with RNA; DNase B, a Mg++-dependent single-strand specific exonuclease of molecular weight 78,000 daltons active with both ss-DNA and RNA; DNase C, a divalent metal ion-dependent endo-exonuclease of molecular weight 65,000 having single-strand specific endonuclease activity with ss-DNA and RNA and exonuclease activity with ds-DNA. Three mutants which were shown previously to have wide spectra of sensitivities to mutagens, and which exhibited reduced release of DNase activity on sorbose-containing agar test plates (the Nuh phenotype), were deficient relative to the wild-type in the release of these major alkaline DNases into the liquid culture medium. The uvs-3 mutant released only small amounts of DNase A and DNase C; nuh-4 did not release detectable DNase C and released only a very low level of DNase B; uvs-6 released only a low level of DNase A. A nuh mutant (nuh-3) which is not mutagen sensitive relative to the wild-type released low levels of DNase B. On the other hand, an ultraviolet light-sensitive mutant (nuc-2) which does not have the Nuh phenotype was normal in the release of these DNases.", "contents": "Alkaline deoxyribonucleases released from Neurospora crassa mycelia: two activities not released by mutants with multiple sensitivities to mutagens. Three major alkaline deoxyribonuclease (DNase) activities have been identified in sorbose-containing liquid culture medium in which wild-type Neurosporacrassa were grown: DNase A, a Ca++dependent endonuclease of molecular weight 65,000 daltons which has no specificity for single- or double-stranded DNA (ss-DNA or ds-DNA) and no activity with RNA; DNase B, a Mg++-dependent single-strand specific exonuclease of molecular weight 78,000 daltons active with both ss-DNA and RNA; DNase C, a divalent metal ion-dependent endo-exonuclease of molecular weight 65,000 having single-strand specific endonuclease activity with ss-DNA and RNA and exonuclease activity with ds-DNA. Three mutants which were shown previously to have wide spectra of sensitivities to mutagens, and which exhibited reduced release of DNase activity on sorbose-containing agar test plates (the Nuh phenotype), were deficient relative to the wild-type in the release of these major alkaline DNases into the liquid culture medium. The uvs-3 mutant released only small amounts of DNase A and DNase C; nuh-4 did not release detectable DNase C and released only a very low level of DNase B; uvs-6 released only a low level of DNase A. A nuh mutant (nuh-3) which is not mutagen sensitive relative to the wild-type released low levels of DNase B. On the other hand, an ultraviolet light-sensitive mutant (nuc-2) which does not have the Nuh phenotype was normal in the release of these DNases."} {"id": "PMID:154661", "title": "Biochemical changes in the rat brain associated with dinitrophenol-induced brain edema.", "content": "The present paper was designed to the study of cerebral edema induced by intracarotid infusion of dinitrophenol. The determinations included variations in three lysosomal enzymes (acid phosphatase, cathepsin C and beta-glucuronidase), Na+-K+-ATP-ase, changes in cerebral RNA and protein concentrations and the synthesis of these macromolecules in vitro. In experimental brain edema a drastic drop in the activity of lysosomal enzymes took place. The acid phosphatase decreased to less than 30% of controls. Cathepsin C and beta-glucuronidase were reduced about 30% and 50% of control levels respectively. Protein concentration in the cerebral tissue also decreased by more than 50%. The concentration of RNA, RNA synthesis, and the level of Na+-K+-ATP-ase remained unchanged. Protein synthesis was stimulated by 75% (against controls). All these phenomena were suppressed when the animals subjected to the action of dinitrophenol were concomitantly treated with the antiacidotic substance, tris (hydroxymethyl) aminomethane.", "contents": "Biochemical changes in the rat brain associated with dinitrophenol-induced brain edema. The present paper was designed to the study of cerebral edema induced by intracarotid infusion of dinitrophenol. The determinations included variations in three lysosomal enzymes (acid phosphatase, cathepsin C and beta-glucuronidase), Na+-K+-ATP-ase, changes in cerebral RNA and protein concentrations and the synthesis of these macromolecules in vitro. In experimental brain edema a drastic drop in the activity of lysosomal enzymes took place. The acid phosphatase decreased to less than 30% of controls. Cathepsin C and beta-glucuronidase were reduced about 30% and 50% of control levels respectively. Protein concentration in the cerebral tissue also decreased by more than 50%. The concentration of RNA, RNA synthesis, and the level of Na+-K+-ATP-ase remained unchanged. Protein synthesis was stimulated by 75% (against controls). All these phenomena were suppressed when the animals subjected to the action of dinitrophenol were concomitantly treated with the antiacidotic substance, tris (hydroxymethyl) aminomethane."} {"id": "PMID:154662", "title": "Radiologic signs of hip and knee joint degeneration. A potential source of iatrogenesis.", "content": "Bilateral x-ray films of hip joints in 326 and knee joints in 193 asymptomatic patients were analyzed to investigate the prevalence of abnormalities. Degenerative changes, if any, were classified according to severity. Bilateral degeneration of hip or knee joints was found in 20% of the subjects. Thus, caution must be exercised in interpreting radiologic signs of joint degeneration in the absence of clinical evidence.", "contents": "Radiologic signs of hip and knee joint degeneration. A potential source of iatrogenesis. Bilateral x-ray films of hip joints in 326 and knee joints in 193 asymptomatic patients were analyzed to investigate the prevalence of abnormalities. Degenerative changes, if any, were classified according to severity. Bilateral degeneration of hip or knee joints was found in 20% of the subjects. Thus, caution must be exercised in interpreting radiologic signs of joint degeneration in the absence of clinical evidence."} {"id": "PMID:154664", "title": "[Seasonal fluctuations in the electrolyte content in diabetes mellitus].", "content": "Results of examination of 257 patients suffering from diabetes mellitus demonstrated a reduction of sodium, potassium and magnesium content in their plasma. Erythrocytes also displayed a reduction of potassium and magnesium, and some increase of sodium content. Reduction of electrolyte level in the plasma and erythrocytes was more pronounced in winter; the erythrocyte sodium content was less in summer than in winter. The 24-hour sodium potassium and magnesium excretion is increased, during winter in particular. The efficacy of treatment of diabetic patients with panangin and potassium chloride for the purpose of elimination of magnesium and potassium deficiency was demonstrated. A conclusion was drawn on the expediency of using these drugs in the complex treatment of diabetic patients, particularly in winter.", "contents": "[Seasonal fluctuations in the electrolyte content in diabetes mellitus]. Results of examination of 257 patients suffering from diabetes mellitus demonstrated a reduction of sodium, potassium and magnesium content in their plasma. Erythrocytes also displayed a reduction of potassium and magnesium, and some increase of sodium content. Reduction of electrolyte level in the plasma and erythrocytes was more pronounced in winter; the erythrocyte sodium content was less in summer than in winter. The 24-hour sodium potassium and magnesium excretion is increased, during winter in particular. The efficacy of treatment of diabetic patients with panangin and potassium chloride for the purpose of elimination of magnesium and potassium deficiency was demonstrated. A conclusion was drawn on the expediency of using these drugs in the complex treatment of diabetic patients, particularly in winter."} {"id": "PMID:154670", "title": "Assembly of the mitochondrial membrane system: partial sequence of a mitochondrial ATPase gene in Saccharomyces cerevisiae.", "content": "The nucleotide sequence of mitochondrial DNA of a cytoplasmic \"petite\" mutant of Saccharomyces cerevisiae is reported. The DNA has a repeat length of 1060 base pairs and contains a genetic marker (oli-1) for the ATPase proteolipid. The nucleotide sequence reveals the presence of part of the structural gene of the subunit-9 proteolipid of the ATPase complex and an extended A+T-rich region adjacent to the carboxyl-terminal end of the gene. The structural gene sequence agrees with the primary structure of the protein. These studies point out the feasibility of using the DNA of appropriately marked \"petite\" mutants to obtain the sequence of mitochondrial genes.", "contents": "Assembly of the mitochondrial membrane system: partial sequence of a mitochondrial ATPase gene in Saccharomyces cerevisiae. The nucleotide sequence of mitochondrial DNA of a cytoplasmic \"petite\" mutant of Saccharomyces cerevisiae is reported. The DNA has a repeat length of 1060 base pairs and contains a genetic marker (oli-1) for the ATPase proteolipid. The nucleotide sequence reveals the presence of part of the structural gene of the subunit-9 proteolipid of the ATPase complex and an extended A+T-rich region adjacent to the carboxyl-terminal end of the gene. The structural gene sequence agrees with the primary structure of the protein. These studies point out the feasibility of using the DNA of appropriately marked \"petite\" mutants to obtain the sequence of mitochondrial genes."} {"id": "PMID:154671", "title": "Calcium-sensitive regulation of actin-myosin interactions in baby hamster kidney (BHK-21) cells.", "content": "A fraction has been obtained from baby hamster kidney (BHK-21) cells that will stimulate the actin-moderated ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity of both BHK-21 myosin and gizzard smooth muscle myosin. This activation is associated with the specific phosphorylation of the myosin 20,000-dalton light chain. The BHK-21 myosin light chain kinase preparation contains a major protein of approximately 105,000 molecular weight as determined by sodium dodecyl sulfate gel electrophoresis. Both the actin activation and phosphorylation events require the presence of Ca2+ and the so-called modulator or calcium-dependent regulator protein that has been isolated from smooth muscle, brain, and other tissues. On the basis of these results we propose that this kinase system constitutes a Ca2+-dependent regulatory mechanism for myosin-actin interactions in nonmuscle mammalian cells.", "contents": "Calcium-sensitive regulation of actin-myosin interactions in baby hamster kidney (BHK-21) cells. A fraction has been obtained from baby hamster kidney (BHK-21) cells that will stimulate the actin-moderated ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity of both BHK-21 myosin and gizzard smooth muscle myosin. This activation is associated with the specific phosphorylation of the myosin 20,000-dalton light chain. The BHK-21 myosin light chain kinase preparation contains a major protein of approximately 105,000 molecular weight as determined by sodium dodecyl sulfate gel electrophoresis. Both the actin activation and phosphorylation events require the presence of Ca2+ and the so-called modulator or calcium-dependent regulator protein that has been isolated from smooth muscle, brain, and other tissues. On the basis of these results we propose that this kinase system constitutes a Ca2+-dependent regulatory mechanism for myosin-actin interactions in nonmuscle mammalian cells."} {"id": "PMID:154672", "title": "Import of proteins into mitochondria: precursor forms of the extramitochondrially made F1-ATPase subunits in yeast.", "content": "The mitochondrial F1-ATPase consists of five nonidentical subunits that are synthesized outside the mitochondria and imported across both mitochondrial membranes to the matrix side of the inner membrane. In order to study the mechanism of this import, we synthesized the F1-ATPase subunits of yeast either in vitro (in a reticulocyte lysate programmed with yeast RNA) or in vivo (in pulsed and pulsed-chased yeast spheroplasts). Both in vitro and in vivo, each of the three largest ATPase subunits was synthesized as a larger precursor. When the precursors that had been synthesized in vitro were incubated with isolated yeast mitochondria, they were converted to \"mature\" subunits that were no longer susceptible to externally added proteases. The uptake of the subunit into the mitochondria was thus accompanied by conversion of the precursor. Since uptake of precursors into mitochondria was independent of protein synthesis and since the precursors could also be detected in vivo, the transfer of proteins from the cytosol across both mitochondrial membranes does not occur by vectorial translation. Instead, the proteins destined for import are first made outside the mitochondria as precursors and only subsequently transported into the mitochondria. This step is accompanied by proteolytic conversion of the mature subunit.", "contents": "Import of proteins into mitochondria: precursor forms of the extramitochondrially made F1-ATPase subunits in yeast. The mitochondrial F1-ATPase consists of five nonidentical subunits that are synthesized outside the mitochondria and imported across both mitochondrial membranes to the matrix side of the inner membrane. In order to study the mechanism of this import, we synthesized the F1-ATPase subunits of yeast either in vitro (in a reticulocyte lysate programmed with yeast RNA) or in vivo (in pulsed and pulsed-chased yeast spheroplasts). Both in vitro and in vivo, each of the three largest ATPase subunits was synthesized as a larger precursor. When the precursors that had been synthesized in vitro were incubated with isolated yeast mitochondria, they were converted to \"mature\" subunits that were no longer susceptible to externally added proteases. The uptake of the subunit into the mitochondria was thus accompanied by conversion of the precursor. Since uptake of precursors into mitochondria was independent of protein synthesis and since the precursors could also be detected in vivo, the transfer of proteins from the cytosol across both mitochondrial membranes does not occur by vectorial translation. Instead, the proteins destined for import are first made outside the mitochondria as precursors and only subsequently transported into the mitochondria. This step is accompanied by proteolytic conversion of the mature subunit."} {"id": "PMID:154673", "title": "Interesting and unusual features in the sequence of Neurospora crassa mitochondrial tyrosine transfer RNA.", "content": "The mitochondrial tyrosine tRNA from Neurospora crassa has been sequenced and found to have several interesting features: (i) It resembles prokaryotic rather than eukaryotic tyrosine tRNAs in that it possesses a large variable loop (loop III); moreover, it can be quantitatively aminoacylated by Escherichia coli tyrosyl-tRNA synthetase but not by yeast tyrosyl-tRNA synthetase. (ii) This tRNA differs from all tRNA's sequenced to date in lacking the A residue at position 14 and the constant purine residue at position 15, two nucleosides that have been found so far in loop I of all tRNA's and that have been implicated in base-base tertiary interactions, respectively, with the universal U residue at position 8 and the constant pyrimidine residue at the end of loop III. (iii) Unlike the N. crassa mitochondrial initiator tRNA, this tRNA contains the usual TpsiC sequence in loop IV and the highly conserved GG sequence in loop I common to other tRNAs.", "contents": "Interesting and unusual features in the sequence of Neurospora crassa mitochondrial tyrosine transfer RNA. The mitochondrial tyrosine tRNA from Neurospora crassa has been sequenced and found to have several interesting features: (i) It resembles prokaryotic rather than eukaryotic tyrosine tRNAs in that it possesses a large variable loop (loop III); moreover, it can be quantitatively aminoacylated by Escherichia coli tyrosyl-tRNA synthetase but not by yeast tyrosyl-tRNA synthetase. (ii) This tRNA differs from all tRNA's sequenced to date in lacking the A residue at position 14 and the constant purine residue at position 15, two nucleosides that have been found so far in loop I of all tRNA's and that have been implicated in base-base tertiary interactions, respectively, with the universal U residue at position 8 and the constant pyrimidine residue at the end of loop III. (iii) Unlike the N. crassa mitochondrial initiator tRNA, this tRNA contains the usual TpsiC sequence in loop IV and the highly conserved GG sequence in loop I common to other tRNAs."} {"id": "PMID:154679", "title": "Resection of a massive arteriovenous malformation of the head and neck.", "content": "We report a patient with a massive arteriovenous malformation of the head and neck treated by surgical extirpation of the lesion. Arteriography, hypotensive hypothermic anesthesia, and the intraoperative use of the Doppler flowmeter were most helpful in this case.", "contents": "Resection of a massive arteriovenous malformation of the head and neck. We report a patient with a massive arteriovenous malformation of the head and neck treated by surgical extirpation of the lesion. Arteriography, hypotensive hypothermic anesthesia, and the intraoperative use of the Doppler flowmeter were most helpful in this case."} {"id": "PMID:154676", "title": "Studies concerning the significance of orthogonal ECG changes with age in normal men and in arterial hypertension without congestive cardiac failure in men past forty.", "content": "Great ECG changes (Frank system) with age were found in normal men. ECG diagnostic criteria valid in Romania were studied by multivariate analyses in men aged 40--60 suffering from hypertension (Hyp) without cardiac congestive failure (CCF), out of which one group with left ventricular hypertrophy (LVH) and another one without it. Echocardiographic studies in normal and hypertensive men past forty, as well as studies in experimental Hyp with LVH and without CCF were carried out. Heart X-ray evaluation is not a functional one. Some non-invasive methods in men do not determine an accurate evaluation of LV performance. The increase of LV muscular mass alone cannot explain the ECG changes in LVH in Hyp without CCF. Two conditional adaptive mechanisms: the liberation of catecholamines from the myocardium storage, induced by the pressure overload stress, and the increase of intracellular Ca++ influx could contribute to the respective ECG changes.", "contents": "Studies concerning the significance of orthogonal ECG changes with age in normal men and in arterial hypertension without congestive cardiac failure in men past forty. Great ECG changes (Frank system) with age were found in normal men. ECG diagnostic criteria valid in Romania were studied by multivariate analyses in men aged 40--60 suffering from hypertension (Hyp) without cardiac congestive failure (CCF), out of which one group with left ventricular hypertrophy (LVH) and another one without it. Echocardiographic studies in normal and hypertensive men past forty, as well as studies in experimental Hyp with LVH and without CCF were carried out. Heart X-ray evaluation is not a functional one. Some non-invasive methods in men do not determine an accurate evaluation of LV performance. The increase of LV muscular mass alone cannot explain the ECG changes in LVH in Hyp without CCF. Two conditional adaptive mechanisms: the liberation of catecholamines from the myocardium storage, induced by the pressure overload stress, and the increase of intracellular Ca++ influx could contribute to the respective ECG changes."} {"id": "PMID:154682", "title": "Studies on human blood platelets in affective disorder.", "content": "Platelets were examined to enable a simultaneous investigation to be made of indolylamine and electrolyte metabolism in affective disorder. No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared with appropriate controls. A reduced Vmax and y for the 5-hydroxy-tryptamine uptake process into platelets was observed in both unipolar and bipolar depressed groups. The Km for this process was not significantly different in any of the patients from that found in control subjects. Lithium therapy was shown not to influence significantly any of the platelet parameters examined. It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorder, i.e. reduced Na+ + K+ - ATPase activity in erythrocytes in depression, is not common to all peripheral cells and may or may not reflect central nervous system changes.", "contents": "Studies on human blood platelets in affective disorder. Platelets were examined to enable a simultaneous investigation to be made of indolylamine and electrolyte metabolism in affective disorder. No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared with appropriate controls. A reduced Vmax and y for the 5-hydroxy-tryptamine uptake process into platelets was observed in both unipolar and bipolar depressed groups. The Km for this process was not significantly different in any of the patients from that found in control subjects. Lithium therapy was shown not to influence significantly any of the platelet parameters examined. It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorder, i.e. reduced Na+ + K+ - ATPase activity in erythrocytes in depression, is not common to all peripheral cells and may or may not reflect central nervous system changes."} {"id": "PMID:154678", "title": "Effects of some prostaglandins on the main phosphorylating, electron transporting and peroxidative systems of the erythrocyte membrane.", "content": "Investigations regarding the main biochemical systems of the erythrocyte membrane were performed on rat erythrocyte ghosts after treating the animals with PGA1, PGE1 and PGF2alpha. These investigations have shown that the prostaglandins which were found to induce changes in the erythrocyte flexibility (PGE1 and PGF2ALPHA) also induce significant changes in the concentrations of lipid peroxides, SH groups, proteins and nicotinamide adenine nucleotides, as well as in the activity of some electron transportors belonging to the nicotinamide proteins, in the erythrocyte membrane.", "contents": "Effects of some prostaglandins on the main phosphorylating, electron transporting and peroxidative systems of the erythrocyte membrane. Investigations regarding the main biochemical systems of the erythrocyte membrane were performed on rat erythrocyte ghosts after treating the animals with PGA1, PGE1 and PGF2alpha. These investigations have shown that the prostaglandins which were found to induce changes in the erythrocyte flexibility (PGE1 and PGF2ALPHA) also induce significant changes in the concentrations of lipid peroxides, SH groups, proteins and nicotinamide adenine nucleotides, as well as in the activity of some electron transportors belonging to the nicotinamide proteins, in the erythrocyte membrane."} {"id": "PMID:154683", "title": "Voluntary control of electrogastric activity.", "content": "The tonic component of the electrogastrogram (EGG) has been shown to differentiate duodenal ulcer patients from healthy individuals (15). It has therefore been of considerable interest to investigate the possibility that individuals can learn to modify electrogastric activity. Using a discriminative conditioning paradigm with analogue feedback (Experiment I), subjects were generally unsuccessful at controlling tonic EGG activity. However, when the conditioning paradigm was altered (Experiment II) it was clear that subjects were able to modify specific electrogastric changes. In addition to EGG, heart rate, respiration, abdominal muscle activity, and digital blood flow were measured in order to assess the physiological concomitants of learned control of gastrointestinal activity. Subjects who evidenced discriminative control also showed the least amount of abdominal muscle activity and reported being the most relaxed. The results of these studies suggest that exploration of the physiological processes underlying the electrical activity of the gastrointestinal system and the ability of individuals to modify this activity may lead to significant clinical and theoretical advances.", "contents": "Voluntary control of electrogastric activity. The tonic component of the electrogastrogram (EGG) has been shown to differentiate duodenal ulcer patients from healthy individuals (15). It has therefore been of considerable interest to investigate the possibility that individuals can learn to modify electrogastric activity. Using a discriminative conditioning paradigm with analogue feedback (Experiment I), subjects were generally unsuccessful at controlling tonic EGG activity. However, when the conditioning paradigm was altered (Experiment II) it was clear that subjects were able to modify specific electrogastric changes. In addition to EGG, heart rate, respiration, abdominal muscle activity, and digital blood flow were measured in order to assess the physiological concomitants of learned control of gastrointestinal activity. Subjects who evidenced discriminative control also showed the least amount of abdominal muscle activity and reported being the most relaxed. The results of these studies suggest that exploration of the physiological processes underlying the electrical activity of the gastrointestinal system and the ability of individuals to modify this activity may lead to significant clinical and theoretical advances."} {"id": "PMID:154688", "title": "The effect of EDTA on the histochemical myofibrillar ATPase reaction.", "content": "The effects of different salts and concentrations of ethylene diamine tetraacetic acid (EDTA) on the histochemically demonstrable myofibrillar ATPase reaction have been investigated. Serial frozen sections from the vastus lateralis muscle of rats, rabbits and guinea pigs were treated with cold (4 degrees) dipotassium EDTA solution and then incubated for myofibrillar ATPase activity. The results showed that all type I muscle fibres exhibited enhanced ATPase activity while type II fibres demonstrated either very low, moderate or intense reaction suggesting the existence of three different sub-populations. None of these effects was observed if the sections were immersed in magnesium chloride solution after preincubation in cold diK+ EDTA. Preincubation in cold non-ionic EDTA, disodium or tetrasodium EDTA did not affect the regular ATPase reaction pattern, while preincubation in warm (19 degrees--21 degrees C) solutions of the same salts resulted in reversal of the regular pattern of ATPase activity. The present histochemical data emphasise the importance of K+, Mg++ and temperature during preincubation of muscle fibres in EDTA before the demonstration of myofibrillar ATPase activity. Moreover, preincubation in a cold solution of diK+ EDTA may be valuable in the histochemical detection of distinct sub-populations of type II muscle fibres and certainly distinguished between type II white and type II red.", "contents": "The effect of EDTA on the histochemical myofibrillar ATPase reaction. The effects of different salts and concentrations of ethylene diamine tetraacetic acid (EDTA) on the histochemically demonstrable myofibrillar ATPase reaction have been investigated. Serial frozen sections from the vastus lateralis muscle of rats, rabbits and guinea pigs were treated with cold (4 degrees) dipotassium EDTA solution and then incubated for myofibrillar ATPase activity. The results showed that all type I muscle fibres exhibited enhanced ATPase activity while type II fibres demonstrated either very low, moderate or intense reaction suggesting the existence of three different sub-populations. None of these effects was observed if the sections were immersed in magnesium chloride solution after preincubation in cold diK+ EDTA. Preincubation in cold non-ionic EDTA, disodium or tetrasodium EDTA did not affect the regular ATPase reaction pattern, while preincubation in warm (19 degrees--21 degrees C) solutions of the same salts resulted in reversal of the regular pattern of ATPase activity. The present histochemical data emphasise the importance of K+, Mg++ and temperature during preincubation of muscle fibres in EDTA before the demonstration of myofibrillar ATPase activity. Moreover, preincubation in a cold solution of diK+ EDTA may be valuable in the histochemical detection of distinct sub-populations of type II muscle fibres and certainly distinguished between type II white and type II red."} {"id": "PMID:154725", "title": "[Relationship between some health indicators of physical, mental well-being and handicaps in the aged (author's transl)].", "content": "The health status of 1,025 senior urban citizens was determined by a questionnaire based on the subjects' view of physical, mental and global well-being and of dependency (indicators of Belloc and all., Berkman, Grogono and Woodgate, Linn). The significant correlation was observed between different health indicators. However, these correlations are not strong enough to allow the explanation of one indicator by the others. The mental well-being is most independent of all other health measurements under study. The valuable information on the prevalence of some health limitations in the population is given by the constituents of the health indexes used. On the contrary, a more complete view of the health of the population should be obtained by the non correlated methods of measurement. The situation may vary following the epidemiological characteristics of the population studied.", "contents": "[Relationship between some health indicators of physical, mental well-being and handicaps in the aged (author's transl)]. The health status of 1,025 senior urban citizens was determined by a questionnaire based on the subjects' view of physical, mental and global well-being and of dependency (indicators of Belloc and all., Berkman, Grogono and Woodgate, Linn). The significant correlation was observed between different health indicators. However, these correlations are not strong enough to allow the explanation of one indicator by the others. The mental well-being is most independent of all other health measurements under study. The valuable information on the prevalence of some health limitations in the population is given by the constituents of the health indexes used. On the contrary, a more complete view of the health of the population should be obtained by the non correlated methods of measurement. The situation may vary following the epidemiological characteristics of the population studied."} {"id": "PMID:154747", "title": "Sodium cromoglycate and ipratropium bromide in exercise-induced asthma.", "content": "In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the baseline ratio of expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) to V50air was over 1.20 and they were called responders; the remaining five patients were called non-responders. There was a significantly lower baseline maximum mid-expiratory flow rate (MMEF) in non-responders (P less than 0.02) as compared to responders but no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Sodium cromoglycate (P less than 0.02), ipratropium bromide (P less than 0.01), and ipratropium bromide plus spdium cromoglycate (P less than 0.01) all significantly inhibited the percentage fall in FEV1 after exercise in the responders. Ipratropium bromide had no preventive action on non-responders, unlike sodium cromoglycate (P less than 0.05) and ipratropium bromide plus sodium cromoglycate (P less than 0.02). It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics, whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways.", "contents": "Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the baseline ratio of expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) to V50air was over 1.20 and they were called responders; the remaining five patients were called non-responders. There was a significantly lower baseline maximum mid-expiratory flow rate (MMEF) in non-responders (P less than 0.02) as compared to responders but no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Sodium cromoglycate (P less than 0.02), ipratropium bromide (P less than 0.01), and ipratropium bromide plus spdium cromoglycate (P less than 0.01) all significantly inhibited the percentage fall in FEV1 after exercise in the responders. Ipratropium bromide had no preventive action on non-responders, unlike sodium cromoglycate (P less than 0.05) and ipratropium bromide plus sodium cromoglycate (P less than 0.02). It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics, whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways."} {"id": "PMID:154748", "title": "The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis.", "content": "In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice.", "contents": "The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis. In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice."} {"id": "PMID:154749", "title": "Natural oestrogen in the female climacteric--influence on blood coagulation and fibrinolysis.", "content": "The aim of the present study was to investigate the effect on blood coagulation and fibrinolysis of a natural oestrogen preparation, piperazine oestrone sulphate, prospectively in menopausal women. Scopolamine was given to the control group. The women were investigated before and during treatment with regard to factors VIII, VII, X, V, fibrinopeptide A, antithrombin III, plasminogen, rapid antiplasmin and alpha 1-antitrypsin. There was no significant change towards hypercoagulability or decreased fibrinolysis in any group. In the oestrogen group, however, a tendency towards an increased level of plasminogen and a decreased level of antiplasmin was demonstrated. In the scopolamine group there was an unexpected fall in factors X and V and also in plasminogen and alpha 1-antitrypsin. A low level of some blood coagulation factors in some of the women before treatment is somewhat astonishing; none of them had any history of excessive bleeding.", "contents": "Natural oestrogen in the female climacteric--influence on blood coagulation and fibrinolysis. The aim of the present study was to investigate the effect on blood coagulation and fibrinolysis of a natural oestrogen preparation, piperazine oestrone sulphate, prospectively in menopausal women. Scopolamine was given to the control group. The women were investigated before and during treatment with regard to factors VIII, VII, X, V, fibrinopeptide A, antithrombin III, plasminogen, rapid antiplasmin and alpha 1-antitrypsin. There was no significant change towards hypercoagulability or decreased fibrinolysis in any group. In the oestrogen group, however, a tendency towards an increased level of plasminogen and a decreased level of antiplasmin was demonstrated. In the scopolamine group there was an unexpected fall in factors X and V and also in plasminogen and alpha 1-antitrypsin. A low level of some blood coagulation factors in some of the women before treatment is somewhat astonishing; none of them had any history of excessive bleeding."} {"id": "PMID:154763", "title": "Ultrastructural evidence of myofibroblasts in pseudomalignant myositis ossificans.", "content": "Seven cases of pseudomalignant ossifying myositis with a typical clinical symptomatology have been reported. None of the cases had experienced an injury. All the lesions were intramuscular and all of them showed a zonal arrangement. Electron microscopy in three cases allowed the demonstration of cells showing morphological features of myofibroblasts and monocytic cells of the macrophage type. These previously unreported features together with the zonal pattern of the lesions indicate their reparative nature.", "contents": "Ultrastructural evidence of myofibroblasts in pseudomalignant myositis ossificans. Seven cases of pseudomalignant ossifying myositis with a typical clinical symptomatology have been reported. None of the cases had experienced an injury. All the lesions were intramuscular and all of them showed a zonal arrangement. Electron microscopy in three cases allowed the demonstration of cells showing morphological features of myofibroblasts and monocytic cells of the macrophage type. These previously unreported features together with the zonal pattern of the lesions indicate their reparative nature."} {"id": "PMID:154764", "title": "The basement membrane in experimentally induced atypias and carcinoma of the uterine cervix in mice. An immunofluorescence study.", "content": "Basement membrane-specific antigens of the squamous epithelium of the uterine cervix were investigated in 19 normal mice, in 7 mice with cervical atypia and in 3 mice with invasive carcinoma. Cervical atypia and carcinoma were induced by local application of benzo(a)pyrene. Basement membrane-specific antigens were demonstrated by immunofluorescence with sera from patients with bullous pemphigoid. Both normal squamous cervical epithelium and atypical cervical epithelium showed the presence of a continuous, clearly delineated basement membrane. Clusters of invasive squamous carcinoma were also surrounded by a fluorescent basement membrane which, however, appear fragmented or discontinuous. The results suggest that the ability of cervical squamous cells to secrete basement membrane antigens is not completely lost during carcinogenesis, thus substantiating our previous observations in the cervix of human subjects.", "contents": "The basement membrane in experimentally induced atypias and carcinoma of the uterine cervix in mice. An immunofluorescence study. Basement membrane-specific antigens of the squamous epithelium of the uterine cervix were investigated in 19 normal mice, in 7 mice with cervical atypia and in 3 mice with invasive carcinoma. Cervical atypia and carcinoma were induced by local application of benzo(a)pyrene. Basement membrane-specific antigens were demonstrated by immunofluorescence with sera from patients with bullous pemphigoid. Both normal squamous cervical epithelium and atypical cervical epithelium showed the presence of a continuous, clearly delineated basement membrane. Clusters of invasive squamous carcinoma were also surrounded by a fluorescent basement membrane which, however, appear fragmented or discontinuous. The results suggest that the ability of cervical squamous cells to secrete basement membrane antigens is not completely lost during carcinogenesis, thus substantiating our previous observations in the cervix of human subjects."} {"id": "PMID:154766", "title": "[Ultrastructural observations on transitional cloacogenic carcinomas of the ano-rectal region (author's transl)].", "content": "The clinical and pathological features of four transitional cloacogenic carcinomas (TCC) are presented with particular reference to electron microscopy. The incidence of this tumour is 1.4% of all ano-rectal neoplasms. Three cases showed a gross appearance similar to the common rectal neoplasms. One tumour presented without an intraluminal lesion, but infiltrated the bowel wall and the anal glands. TCC show a distinct histological pattern. The degree of differentiation of the basic transitional cell component determines the \"grading\" of the lesion. We distinguish between grade I, II and III. Grade I lesions show uniform polygonal cells with only occasional mitotic figures. There is distinct palisading of the nuclei of the peripheral tumour cell layers. Grade II lesions are characterized by partial or total loss of the peripheral palisading. Grade III lesions are extremely anaplastic (\"oat cell\" carcinoma). This histological classification correlates well with the prognosis. Electron microscopic investigation of TCC revealed the ultrastructural features of basal cells. The uniform tumour cells with large nuclei contain tonofibrils, desmosomes and hemi-desmosomes, free ribosomes, and relatively few other organelles. We did not find keratinocytes or keratohyalin granules in these four cases of TCC. It is emphasized that TCC of the ano-rectal region differ fundamentally from the basalcell carcinomas of the skin in their biological behaviour.", "contents": "[Ultrastructural observations on transitional cloacogenic carcinomas of the ano-rectal region (author's transl)]. The clinical and pathological features of four transitional cloacogenic carcinomas (TCC) are presented with particular reference to electron microscopy. The incidence of this tumour is 1.4% of all ano-rectal neoplasms. Three cases showed a gross appearance similar to the common rectal neoplasms. One tumour presented without an intraluminal lesion, but infiltrated the bowel wall and the anal glands. TCC show a distinct histological pattern. The degree of differentiation of the basic transitional cell component determines the \"grading\" of the lesion. We distinguish between grade I, II and III. Grade I lesions show uniform polygonal cells with only occasional mitotic figures. There is distinct palisading of the nuclei of the peripheral tumour cell layers. Grade II lesions are characterized by partial or total loss of the peripheral palisading. Grade III lesions are extremely anaplastic (\"oat cell\" carcinoma). This histological classification correlates well with the prognosis. Electron microscopic investigation of TCC revealed the ultrastructural features of basal cells. The uniform tumour cells with large nuclei contain tonofibrils, desmosomes and hemi-desmosomes, free ribosomes, and relatively few other organelles. We did not find keratinocytes or keratohyalin granules in these four cases of TCC. It is emphasized that TCC of the ano-rectal region differ fundamentally from the basalcell carcinomas of the skin in their biological behaviour."} {"id": "PMID:154767", "title": "Papillary carcinoma of the thyroid gland and atresia of the common bile ducts of a five year old boy.", "content": "We present a case of papillary carcinoma of the thyroid gland with pulmonary metastases in a 5 year old boy. The child also suffered from atresia of the gallbladder and the common bile ducts with biliary cirrhosis of the liver and died from hepatic insufficiency. Possible correlations between childhood thyroid carcinoma and congenital malformations are discussed.", "contents": "Papillary carcinoma of the thyroid gland and atresia of the common bile ducts of a five year old boy. We present a case of papillary carcinoma of the thyroid gland with pulmonary metastases in a 5 year old boy. The child also suffered from atresia of the gallbladder and the common bile ducts with biliary cirrhosis of the liver and died from hepatic insufficiency. Possible correlations between childhood thyroid carcinoma and congenital malformations are discussed."} {"id": "PMID:154771", "title": "[Disorders of phenylalanine and tyrosine metabolism in Down's syndrome].", "content": "Content of phenylalanine and tyrosine was increased in blood serum in mongolism. When 4 patients with mongolism and 10 healthy persons were loaded with 1-phenylalanine, content of the amino acid in blood serum of patients exceeded 1.5--2-fold that found in healthy persons within 4 and 6 hrs after the treatment. The hydroxylation rate of phenylalanine was lower in mongolism as compared to normal state; it corresponded to the rate of phenylalanine hydroxylation in atypical homo- and heterozygote patients bearing \"phenylketonuria\" gene and in patients with viral hepatitis. Concentration of tyrosine was distinctly higher in the impaired patients within 2--6 hrs after the loading as compared with the healthy persons. But content of tyrosine was increased only slightly in patients with mongolism during the loading and excretion of homogentisinic acid with urine was decreased. These data suggest that activity of phenylalanine hydroxylase system is impaired in liver tissue in mongolism. Excretion of phenylpyruvic acid with urine was not observed in the patients and healthy persons both before and during the amino acid loading. The data obtained suggest that impairment of phenylalanine and tyrosine turnover in mongolism appears to be one of the factors responsible for disturbance of neurotransmitter synthesis and to be related to development of mental retardation.", "contents": "[Disorders of phenylalanine and tyrosine metabolism in Down's syndrome]. Content of phenylalanine and tyrosine was increased in blood serum in mongolism. When 4 patients with mongolism and 10 healthy persons were loaded with 1-phenylalanine, content of the amino acid in blood serum of patients exceeded 1.5--2-fold that found in healthy persons within 4 and 6 hrs after the treatment. The hydroxylation rate of phenylalanine was lower in mongolism as compared to normal state; it corresponded to the rate of phenylalanine hydroxylation in atypical homo- and heterozygote patients bearing \"phenylketonuria\" gene and in patients with viral hepatitis. Concentration of tyrosine was distinctly higher in the impaired patients within 2--6 hrs after the loading as compared with the healthy persons. But content of tyrosine was increased only slightly in patients with mongolism during the loading and excretion of homogentisinic acid with urine was decreased. These data suggest that activity of phenylalanine hydroxylase system is impaired in liver tissue in mongolism. Excretion of phenylpyruvic acid with urine was not observed in the patients and healthy persons both before and during the amino acid loading. The data obtained suggest that impairment of phenylalanine and tyrosine turnover in mongolism appears to be one of the factors responsible for disturbance of neurotransmitter synthesis and to be related to development of mental retardation."} {"id": "PMID:154772", "title": "[Effect of thyroid hormones on the calcium pump in sarcoplasmic reticulum].", "content": "In vitro thyroxine inhibited accumulation of Ca2+ by fragments of sarcoplasmic reticulum, isolated from rabbit sceletal muscles. The inhibitory effect of thyroxine was responsible for its direct action on Ca2+ dependent ATPase. Half-maximal inhibition of the enzymatic activity occurred at the same concentrations of thyroxine using both membrane-bound and highly purified solubilized forms of Ca2+-ATPase (15--20 micrometer and 10 micrometer of the hormone, respectively). Triiodothyronine was similar in the effect but not diiodothyrosine, which did not possess the hormonal activity. The data obtained suggest that thyroid hormones affect the mechanism of dephosphorylation in ATP-hydrolase reaction.", "contents": "[Effect of thyroid hormones on the calcium pump in sarcoplasmic reticulum]. In vitro thyroxine inhibited accumulation of Ca2+ by fragments of sarcoplasmic reticulum, isolated from rabbit sceletal muscles. The inhibitory effect of thyroxine was responsible for its direct action on Ca2+ dependent ATPase. Half-maximal inhibition of the enzymatic activity occurred at the same concentrations of thyroxine using both membrane-bound and highly purified solubilized forms of Ca2+-ATPase (15--20 micrometer and 10 micrometer of the hormone, respectively). Triiodothyronine was similar in the effect but not diiodothyrosine, which did not possess the hormonal activity. The data obtained suggest that thyroid hormones affect the mechanism of dephosphorylation in ATP-hydrolase reaction."} {"id": "PMID:154777", "title": "[Omphalocele and gastroschisis: clinical differences and surgical considerations. A ten year review (author's transl)].", "content": "31 infants with anterior abdominal wall defects were treated over the past 10 years. Despite the falling birth rate gastroschisis occurred almost twice as often as omphalocele (19 and 12 cases, respectively). The mortality rate of 71% in omphalocele were related to large defects, rupture of the sac and associated cardiac malformations. The 73% incidence of prematurity, additional malformations and sepsis contributed to the mortality rate of 58% in gastroschisis.", "contents": "[Omphalocele and gastroschisis: clinical differences and surgical considerations. A ten year review (author's transl)]. 31 infants with anterior abdominal wall defects were treated over the past 10 years. Despite the falling birth rate gastroschisis occurred almost twice as often as omphalocele (19 and 12 cases, respectively). The mortality rate of 71% in omphalocele were related to large defects, rupture of the sac and associated cardiac malformations. The 73% incidence of prematurity, additional malformations and sepsis contributed to the mortality rate of 58% in gastroschisis."} {"id": "PMID:154778", "title": "[Clinical results and hormonal aspects of the treatment of virilizing symptoms in women with cyproterone acetate (author's transl)].", "content": "28 cases of moderate to severe hirsutism, two cases of acne and one case of axilary hidrosadenitis were tested continuously on average over 6 months by the daily administration of 100 mg cyproterone acetate. This drug was then given together with 1-2 mg oestradiol valerate over a further 6 month period by reversed sequential therapy. The effect of treatment was judged as being moderate only in 7 cases of idiopathic and one case of adrenal hirsutism and good in the remaining cases. However, this regimen caused a marked lowering of the urinary dehydroepiandrosterone sulphate and low polar oestrogen levels and also the plasma testosterone level. At the same time, according to preliminary results, the fraction of sex hormone binding globulin was raised. The plasma hydrocortisone level was depressed by about 20%. The fractions of 17-KS and 17-KGS decreased slightly at first, but then returned to normal. The side effects of continuous treatment were mainly gestagenic and of reversed sequential therapy mainly oestrogenic in nature. The continuation rate was 81% during a treatment period of two years.", "contents": "[Clinical results and hormonal aspects of the treatment of virilizing symptoms in women with cyproterone acetate (author's transl)]. 28 cases of moderate to severe hirsutism, two cases of acne and one case of axilary hidrosadenitis were tested continuously on average over 6 months by the daily administration of 100 mg cyproterone acetate. This drug was then given together with 1-2 mg oestradiol valerate over a further 6 month period by reversed sequential therapy. The effect of treatment was judged as being moderate only in 7 cases of idiopathic and one case of adrenal hirsutism and good in the remaining cases. However, this regimen caused a marked lowering of the urinary dehydroepiandrosterone sulphate and low polar oestrogen levels and also the plasma testosterone level. At the same time, according to preliminary results, the fraction of sex hormone binding globulin was raised. The plasma hydrocortisone level was depressed by about 20%. The fractions of 17-KS and 17-KGS decreased slightly at first, but then returned to normal. The side effects of continuous treatment were mainly gestagenic and of reversed sequential therapy mainly oestrogenic in nature. The continuation rate was 81% during a treatment period of two years."} {"id": "PMID:154779", "title": "[Tbual Sterilization (author's transl)].", "content": "During the years 1975, 1976 and 1977 2481 tubal sterilizations were performed, either simultaneously with gynaecological operations or Caesarian sections, as an independent operation post partum or by laparoscopy. Unipolar, bipolar or thermocoagulation was used for tubal occlusion. Primary surgical complications occurred in 0.36% of the patients. Until March 31st, 1978 6 women (0.24%) became pregnant after tubal coagulation; so far 2 women have asked for reversal of the operation. From the surgical point of view, on the basis of the basis of these figures, it is a low-risk, dependable (Pearl index 0.13), irreversible method of contraception.", "contents": "[Tbual Sterilization (author's transl)]. During the years 1975, 1976 and 1977 2481 tubal sterilizations were performed, either simultaneously with gynaecological operations or Caesarian sections, as an independent operation post partum or by laparoscopy. Unipolar, bipolar or thermocoagulation was used for tubal occlusion. Primary surgical complications occurred in 0.36% of the patients. Until March 31st, 1978 6 women (0.24%) became pregnant after tubal coagulation; so far 2 women have asked for reversal of the operation. From the surgical point of view, on the basis of the basis of these figures, it is a low-risk, dependable (Pearl index 0.13), irreversible method of contraception."} {"id": "PMID:154782", "title": "[The S\u00e9zary syndrome--an erythrodermic T-cell-lymphoma].", "content": "Report on a 75-year-old patient with S\u00e9zary syndrome which is characterized by the following leading symptoms: Erythrodermia, leukocytosis, circulating atypical lymphocytes with cerebriformous nuclei (S\u00e9zary cells) and swollen lymph nodes. Light microscopic and electron microscopic findings refer to a transitory situation of the S\u00e9zary cells from the reactive character to the (pre)neoplastic one. The disease is classified by T-(helper)cells as a low grade non-Hodgkin-lymphoma in parallel to mycosis fungoides and in general it finishes lethally after a course of 5 to 8 years. Apart from local steroid ointments and UV-irradiations the internal application of steroids, in the late stage if necessary in combination with cytostatics is recommended for therapy.", "contents": "[The S\u00e9zary syndrome--an erythrodermic T-cell-lymphoma]. Report on a 75-year-old patient with S\u00e9zary syndrome which is characterized by the following leading symptoms: Erythrodermia, leukocytosis, circulating atypical lymphocytes with cerebriformous nuclei (S\u00e9zary cells) and swollen lymph nodes. Light microscopic and electron microscopic findings refer to a transitory situation of the S\u00e9zary cells from the reactive character to the (pre)neoplastic one. The disease is classified by T-(helper)cells as a low grade non-Hodgkin-lymphoma in parallel to mycosis fungoides and in general it finishes lethally after a course of 5 to 8 years. Apart from local steroid ointments and UV-irradiations the internal application of steroids, in the late stage if necessary in combination with cytostatics is recommended for therapy."} {"id": "PMID:154783", "title": "[Transient systolic anterior movement of the mitral valve (SAM) without asymmetric septal hypertrophy (case report with post-mortem examination) (author's transl)].", "content": "Typical SAM of the mitral valve was detected by echocardiography in a 71-year-old patient with acute myocardial infarction. The patient showed auscultation signs of IHSS and was digitalized and hypovolemic secondary to diarrhea. Following rehydration and digitalis being discontinued, SAM was no longer seen. There were no signs of IHSS at post-mortem examination. This case demonstrates that obstruction of left ventricular outflow tract together with echocardiographical findings of SAM and the typical clinical signs of IHSSS may be observed without the presence of asymmetric septal hypertrophy. This supports the hypothesis that ejection dynamics in a small and asynergically contracting left ventricle may contribute substantially to the appearance of SAM. On the other hand echocardiographic findings of SAM without asymmetric septal hypertrophy may not exclude symptoms of IHSS.", "contents": "[Transient systolic anterior movement of the mitral valve (SAM) without asymmetric septal hypertrophy (case report with post-mortem examination) (author's transl)]. Typical SAM of the mitral valve was detected by echocardiography in a 71-year-old patient with acute myocardial infarction. The patient showed auscultation signs of IHSS and was digitalized and hypovolemic secondary to diarrhea. Following rehydration and digitalis being discontinued, SAM was no longer seen. There were no signs of IHSS at post-mortem examination. This case demonstrates that obstruction of left ventricular outflow tract together with echocardiographical findings of SAM and the typical clinical signs of IHSSS may be observed without the presence of asymmetric septal hypertrophy. This supports the hypothesis that ejection dynamics in a small and asynergically contracting left ventricle may contribute substantially to the appearance of SAM. On the other hand echocardiographic findings of SAM without asymmetric septal hypertrophy may not exclude symptoms of IHSS."} {"id": "PMID:154798", "title": "[Treatment of experimental immune complex nephritis with indomethacin].", "content": "Functional, histological and immune-histological examination were performed in altogether 64 Wistar-rats, in order to control the effect of a therapy with 2 mg/kg per body weight indomethazine lasting 2 months at the model of an experimental immune complex nephritis. In 44 rats after presensibilisation an immune complex nephritis was performed by intraperitoneal injections with human serum albumin which were repeated three times a week. 24 glomerulonephritis animals and other 20 animals without glomerulonephritis were daily administered indomethazin through a tube probe, the remaining 20 animals with glomerulonephritis served as untreated control groups. The excretion function of the kidney was tested before the beginning of the experiment, 2 weeks after the beginning of the therapy and the regular serum injections, respectively, and before the end of the experiment by determination of the biological half-life period of 131J-hippuran. In every case one day before this the proteinuria during 24 hours was determined. At the end of the experiment the kidneys were examined histologically and immune-histologically. The results showed that indomethazin does not lead to a clear influence on the proteinuria in the immune complex nephritis of the rat. The excretion of 131J-hippuran was significantly restricted, whereas the histological and immune-histological preparations in the animals with foreign serum injections showed clear changes of the glomeruli in the sense of an early stage of the immune complex nephritis, however, they did not show any essential influence by indomethazin. That is, indomethazin had altogether no favourable effect on the immune complex nephritis of the rat.", "contents": "[Treatment of experimental immune complex nephritis with indomethacin]. Functional, histological and immune-histological examination were performed in altogether 64 Wistar-rats, in order to control the effect of a therapy with 2 mg/kg per body weight indomethazine lasting 2 months at the model of an experimental immune complex nephritis. In 44 rats after presensibilisation an immune complex nephritis was performed by intraperitoneal injections with human serum albumin which were repeated three times a week. 24 glomerulonephritis animals and other 20 animals without glomerulonephritis were daily administered indomethazin through a tube probe, the remaining 20 animals with glomerulonephritis served as untreated control groups. The excretion function of the kidney was tested before the beginning of the experiment, 2 weeks after the beginning of the therapy and the regular serum injections, respectively, and before the end of the experiment by determination of the biological half-life period of 131J-hippuran. In every case one day before this the proteinuria during 24 hours was determined. At the end of the experiment the kidneys were examined histologically and immune-histologically. The results showed that indomethazin does not lead to a clear influence on the proteinuria in the immune complex nephritis of the rat. The excretion of 131J-hippuran was significantly restricted, whereas the histological and immune-histological preparations in the animals with foreign serum injections showed clear changes of the glomeruli in the sense of an early stage of the immune complex nephritis, however, they did not show any essential influence by indomethazin. That is, indomethazin had altogether no favourable effect on the immune complex nephritis of the rat."} {"id": "PMID:154816", "title": "[Immunoglobulin content in persons with a varying donor record].", "content": "The blood level of IgA, IgG Igm, and protein in male donors was studied in connection with the duration of the donor's activity. The content of the main blood immunoglobulin classes and proteins depended significantly on the duration of the donor's activity. Therefore it is not recommended to use donors as control group in determining the immunoglobulin level in the blood.", "contents": "[Immunoglobulin content in persons with a varying donor record]. The blood level of IgA, IgG Igm, and protein in male donors was studied in connection with the duration of the donor's activity. The content of the main blood immunoglobulin classes and proteins depended significantly on the duration of the donor's activity. Therefore it is not recommended to use donors as control group in determining the immunoglobulin level in the blood."} {"id": "PMID:154817", "title": "[Determinant factor and pathogenesis of multiple sclerosis].", "content": "A clinico-epidemiological and genealogical analysis of 182 patients with disseminated sclerosis, living in climatogeographical conditions of Tadjikistan permits to assume that disseminated sclerosis is an exogenous intrauterine (but not hereditary!), acquired monoetiological disease. At the basis of the pathogenesis lies an ectodermal microdysgenesia with a selective lesion of the embryo oligodendroglia system and an eventual disturbance of postnatal myelinopoesis. This condition is due to an exogenous-mutagen (toxico-allergic) action of the respective climatogeographical regions of \"risk\" in relation to disseminated sclerosis.", "contents": "[Determinant factor and pathogenesis of multiple sclerosis]. A clinico-epidemiological and genealogical analysis of 182 patients with disseminated sclerosis, living in climatogeographical conditions of Tadjikistan permits to assume that disseminated sclerosis is an exogenous intrauterine (but not hereditary!), acquired monoetiological disease. At the basis of the pathogenesis lies an ectodermal microdysgenesia with a selective lesion of the embryo oligodendroglia system and an eventual disturbance of postnatal myelinopoesis. This condition is due to an exogenous-mutagen (toxico-allergic) action of the respective climatogeographical regions of \"risk\" in relation to disseminated sclerosis."} {"id": "PMID:154818", "title": "Modification of yeast phosphofructokinase by trypsin and subtilisin in the presence of effectors.", "content": "Yeast phosphofructokinase was subjected to limited proteolysis by trypsin in the presence of different effectors. It could be demonstrated that the substrates MgATP and fructose-6-phosphate are able to protect the enzyme from inactivation by trypsin. Other effectors like AMP, ADP, phosphoenolpyruvate, citrate and ammonium ions exhibit only negligible effects. During the first step of degradation consisting in the conversion of the subunits from Mr 120,000 to 90,000 no significant effects of the substrates and effectors on the proteolytic inactivation of yeast phosphofructokinase can be observed. In the presence of ATP as well as of ADP the sensitivity of the enzyme against ATP inhibition is either not or only slightly influenced by proteolytic modification. The modified enzyme retains its sensitivity against activation by AMP, independently of whether effectors are present or absent during proteolysis. The kinetic parameters of the enzyme modified by subtilisin in the presence of ATP or of fructose-6-phosphate have been determined.", "contents": "Modification of yeast phosphofructokinase by trypsin and subtilisin in the presence of effectors. Yeast phosphofructokinase was subjected to limited proteolysis by trypsin in the presence of different effectors. It could be demonstrated that the substrates MgATP and fructose-6-phosphate are able to protect the enzyme from inactivation by trypsin. Other effectors like AMP, ADP, phosphoenolpyruvate, citrate and ammonium ions exhibit only negligible effects. During the first step of degradation consisting in the conversion of the subunits from Mr 120,000 to 90,000 no significant effects of the substrates and effectors on the proteolytic inactivation of yeast phosphofructokinase can be observed. In the presence of ATP as well as of ADP the sensitivity of the enzyme against ATP inhibition is either not or only slightly influenced by proteolytic modification. The modified enzyme retains its sensitivity against activation by AMP, independently of whether effectors are present or absent during proteolysis. The kinetic parameters of the enzyme modified by subtilisin in the presence of ATP or of fructose-6-phosphate have been determined."} {"id": "PMID:154820", "title": "A comparative study of liver blood flow using 133Xenon clearance and electromagnetic flowmeter measurements.", "content": "Recent work has shown that the slow components of the multiexponential clearance of 133Xenon from the liver are generated by radioactive gas in the stomach and intestines, and that the true intraphepatic clearance is monoexponential (Mackenzie et al., 1976). In the present study, liver blood flow calculated from the fast component of the 133Xenon clearance curve was compared with the total hepatic flow recorded with electromagnetic flow probes on the portal vein and hepatic artery in 8 dogs. Injections of isotope were made intoe the portal vein, and the clearance curves treated simply as biexponentials. A total of 50 pairs of blood flow measurements with the two techniques was obtained over a range of values from 80 to 1400 ml/min, and a close correlation found between them (r = 0.91). This result shows that when the clearance rate of the fast component is used for the flow calculation, the 133Xenon clearance technique provides an accurate measure of liver blood flow.", "contents": "A comparative study of liver blood flow using 133Xenon clearance and electromagnetic flowmeter measurements. Recent work has shown that the slow components of the multiexponential clearance of 133Xenon from the liver are generated by radioactive gas in the stomach and intestines, and that the true intraphepatic clearance is monoexponential (Mackenzie et al., 1976). In the present study, liver blood flow calculated from the fast component of the 133Xenon clearance curve was compared with the total hepatic flow recorded with electromagnetic flow probes on the portal vein and hepatic artery in 8 dogs. Injections of isotope were made intoe the portal vein, and the clearance curves treated simply as biexponentials. A total of 50 pairs of blood flow measurements with the two techniques was obtained over a range of values from 80 to 1400 ml/min, and a close correlation found between them (r = 0.91). This result shows that when the clearance rate of the fast component is used for the flow calculation, the 133Xenon clearance technique provides an accurate measure of liver blood flow."} {"id": "PMID:154822", "title": "Humoral influences on local blood flow and external secretion of the resting dog pancreas.", "content": "Graded doses of glucagon (2--8 microgram/kg b. w.), prostaglandin E1 (PGE1) (125--1000 ng/kg b. w.), caerulein (1--32 ng/kg b. w.) and a synthetic C-terminal octapeptide of cholecystokinin-pancreozymin (CCK--PZ) 50--400 ng/kg b. w.) were infused into the superior pancreatioduodenal artery in chloralose-anaesthetized dogs to study the effect on blood flow and external secretion of the resting pancreas. Local blood flow was measured by a heated thermocouple inserted into pancreatic tissue supplied by the superior pancreaticoduodenal artery. Blood flow through this artery was measured by electromagnetic flowmeter. Juice was collected from the cannulated main pancreatic duct. Each of the four agents significantly increased pancreatic blood flow. There was a linear correlation between the doses and the blood flow responses. Caerulein and the synthetic C-terminal octapeptide of CCK--PZ increased the amount of secreted juice from the resting pancreas. The C-terminal octapeptide of CCK--PZ elevated the protein concentration of the secreted juice in proportion to the dose. Glucagon and PGE1 did not influence the amount of secreted juice from the resting gland.", "contents": "Humoral influences on local blood flow and external secretion of the resting dog pancreas. Graded doses of glucagon (2--8 microgram/kg b. w.), prostaglandin E1 (PGE1) (125--1000 ng/kg b. w.), caerulein (1--32 ng/kg b. w.) and a synthetic C-terminal octapeptide of cholecystokinin-pancreozymin (CCK--PZ) 50--400 ng/kg b. w.) were infused into the superior pancreatioduodenal artery in chloralose-anaesthetized dogs to study the effect on blood flow and external secretion of the resting pancreas. Local blood flow was measured by a heated thermocouple inserted into pancreatic tissue supplied by the superior pancreaticoduodenal artery. Blood flow through this artery was measured by electromagnetic flowmeter. Juice was collected from the cannulated main pancreatic duct. Each of the four agents significantly increased pancreatic blood flow. There was a linear correlation between the doses and the blood flow responses. Caerulein and the synthetic C-terminal octapeptide of CCK--PZ increased the amount of secreted juice from the resting pancreas. The C-terminal octapeptide of CCK--PZ elevated the protein concentration of the secreted juice in proportion to the dose. Glucagon and PGE1 did not influence the amount of secreted juice from the resting gland."} {"id": "PMID:154823", "title": "Effect of cadmium on changes in concentration of adenine nucleotides induced by mitochondria.", "content": "The effect of Cd2+ on the respiration of rat liver mitochondria was investigated. The uncoupling effect of Cd2+ was partially restored by the addition of Mg2+. The influence of Cd2+ on adenine nucleotide concentrations in the reaction mixture consisting of mitochondria and ATP was also studied using high performance liquid chromatography. In the presence of added Mg2+, a two-fold increase in AMP concentration was brought about by the addition of Cd2+. There was a concomitant decrease in ATP. In the prence of added ADP, an increase in AMP concentration was also brought about by addition of Cd2+. The results are discussed in relation to ATPase and adenylate kinase activity in mitochondria.", "contents": "Effect of cadmium on changes in concentration of adenine nucleotides induced by mitochondria. The effect of Cd2+ on the respiration of rat liver mitochondria was investigated. The uncoupling effect of Cd2+ was partially restored by the addition of Mg2+. The influence of Cd2+ on adenine nucleotide concentrations in the reaction mixture consisting of mitochondria and ATP was also studied using high performance liquid chromatography. In the presence of added Mg2+, a two-fold increase in AMP concentration was brought about by the addition of Cd2+. There was a concomitant decrease in ATP. In the prence of added ADP, an increase in AMP concentration was also brought about by addition of Cd2+. The results are discussed in relation to ATPase and adenylate kinase activity in mitochondria."} {"id": "PMID:154824", "title": "Levels of erythrocyte superoxide dismutase activity in Japanese people.", "content": "Levels of erythrocyte superoxide dismutase (SOD) activitiy in a sample of Japanese people were determined. Blood samples were taken from new-born infants, preschool children, young and old people who had no apparent diseases and also from three anemic patients. Erythrocyte SOD activities in different age groups had a nearly normal distribution. Females had slightly lower activities than males, although the difference was statistically insignificant. The distributions of SOD activities were 12.6 +/- 2.7 (m +/- SD) unit/mg Hb in young people and 11.4 +/- 3.0 in old people, indicating that erythrocyte SOD activity falls with aging. Because of low concentration of hemoglobin, SOD activities of old people expressed as unit/ml blood were much lower than in young people. Three anemic patients had slightly lower SOD activity (unit/mg Gb), but the difference was not significant.", "contents": "Levels of erythrocyte superoxide dismutase activity in Japanese people. Levels of erythrocyte superoxide dismutase (SOD) activitiy in a sample of Japanese people were determined. Blood samples were taken from new-born infants, preschool children, young and old people who had no apparent diseases and also from three anemic patients. Erythrocyte SOD activities in different age groups had a nearly normal distribution. Females had slightly lower activities than males, although the difference was statistically insignificant. The distributions of SOD activities were 12.6 +/- 2.7 (m +/- SD) unit/mg Hb in young people and 11.4 +/- 3.0 in old people, indicating that erythrocyte SOD activity falls with aging. Because of low concentration of hemoglobin, SOD activities of old people expressed as unit/ml blood were much lower than in young people. Three anemic patients had slightly lower SOD activity (unit/mg Gb), but the difference was not significant."} {"id": "PMID:154825", "title": "Fractionation and characterization of euchromatin isolated from mouse ascites sarcoma cells.", "content": "Euchromatin specimen prepared by the usual method formed large clumps and had various shapes under electron microscopy. A method of separation of the euchromatin specimen into chromatin fractions having relatively homogeneous form was examined and partial characterization of these fractions was carried out. The heavy euchromatin fraction was a large network of thin fibrils (about 100 A in diameter) and various thick fibers. The intermediate euchromatin fraction consisted of relatively homogeneous networks of thick knobby fibers (about 250 A in diameter). The light euchromatin fraction had metworks of thick fibers. These chromatin fractions were quantitatively prepared from sonicated nuclei of mouse ascites sarcoma cells. Twenty-one or twenty-two bands of non-histone proteins besides histones were detected in these chromatin fractions by SDS-polyacrylamide gel electrophoresis. There were significant differences in the electrophoretic patterns of non-histone proteins among these chromatin fractions.", "contents": "Fractionation and characterization of euchromatin isolated from mouse ascites sarcoma cells. Euchromatin specimen prepared by the usual method formed large clumps and had various shapes under electron microscopy. A method of separation of the euchromatin specimen into chromatin fractions having relatively homogeneous form was examined and partial characterization of these fractions was carried out. The heavy euchromatin fraction was a large network of thin fibrils (about 100 A in diameter) and various thick fibers. The intermediate euchromatin fraction consisted of relatively homogeneous networks of thick knobby fibers (about 250 A in diameter). The light euchromatin fraction had metworks of thick fibers. These chromatin fractions were quantitatively prepared from sonicated nuclei of mouse ascites sarcoma cells. Twenty-one or twenty-two bands of non-histone proteins besides histones were detected in these chromatin fractions by SDS-polyacrylamide gel electrophoresis. There were significant differences in the electrophoretic patterns of non-histone proteins among these chromatin fractions."} {"id": "PMID:154826", "title": "Accumulation of radioisotopes with tumor affinity. I. Uptake and excretion of 67Ga-citrate in malignant tumors and normal cells.", "content": "Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The time-lapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results of tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cell being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga.", "contents": "Accumulation of radioisotopes with tumor affinity. I. Uptake and excretion of 67Ga-citrate in malignant tumors and normal cells. Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The time-lapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results of tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cell being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga."} {"id": "PMID:154827", "title": "Identification of organic sulfur compounds transferred to fish from petroleum suspension.", "content": "The authors attempted to determine if the organic sulfur compounds usually contained in a crude oil could serve as a marker of oil pollution in fish. Eels (Anguilla Japonica Temminck et Schlegel) were maintained in a controlled laboratory environment of water with a suspension of crude oil. Gas chromatography-mass spectrometry and mass chromatography of eel flesh extract showed the presence of organic sulfur compounds of alkyl-(from mono- to pentametyl) benzothiophenes, dibenzothiophene and alkyl-(from mono- to trimethyl) dibenzothiophenes, and other organic sulfur compounds of alkyl-(from mono- to pentamethyl) naphthalenes.", "contents": "Identification of organic sulfur compounds transferred to fish from petroleum suspension. The authors attempted to determine if the organic sulfur compounds usually contained in a crude oil could serve as a marker of oil pollution in fish. Eels (Anguilla Japonica Temminck et Schlegel) were maintained in a controlled laboratory environment of water with a suspension of crude oil. Gas chromatography-mass spectrometry and mass chromatography of eel flesh extract showed the presence of organic sulfur compounds of alkyl-(from mono- to pentametyl) benzothiophenes, dibenzothiophene and alkyl-(from mono- to trimethyl) dibenzothiophenes, and other organic sulfur compounds of alkyl-(from mono- to pentamethyl) naphthalenes."} {"id": "PMID:154828", "title": "An approach to nutritional therapy of hepatic encephalopathy by normalization of deranged amino acid patterns in serum.", "content": "A mixture with essential and nonessential amino acids high in branched chain amino acids and low in aromatic amino acids (Fischer solution), and another synthetic mixture of branched chain amino acids containing 3 amino acids associated with the urea cycle (Hep-OU) were infused to control subjects and patients with severe hepatic disease. Alterations in serum aminograms, blood ammonia levels and electroencephalograms following the infusion were studied and compared with those obtained by a commercially available amino acid mixture. Short-term or continuous infusion of a commercially available amino acid solution to cirrhotic patients caused an increase in methionine, phenylalanine and tyrosine and a decrease in branched chain amino acids. These post-infusion results were similar to the patterns seen in hepatic encephalopathy. In cirrhotic patients, infusion of Fischer solution which contains small quantities of methionine and phenylalanine produced an increase in the concentrations of these 2 amino acids, probably because of impaired utilization by the injured liver. No marked alterations in serum aminograms, however, were observed in cirrhotic patients either immediately after, or 3 h after, the end of the Hep-OU infusion. Reduction of methionine, tyrosine and phenylalanine levels and elevation of the molar ratio of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) were significant. The infusion of Hep-OU to patients with liver cirrhosis or subacute hepatitis resulted in clinical and neurological improvements and the restoration of the molar ratio of branched chain amino acids/aromatic amino acids.", "contents": "An approach to nutritional therapy of hepatic encephalopathy by normalization of deranged amino acid patterns in serum. A mixture with essential and nonessential amino acids high in branched chain amino acids and low in aromatic amino acids (Fischer solution), and another synthetic mixture of branched chain amino acids containing 3 amino acids associated with the urea cycle (Hep-OU) were infused to control subjects and patients with severe hepatic disease. Alterations in serum aminograms, blood ammonia levels and electroencephalograms following the infusion were studied and compared with those obtained by a commercially available amino acid mixture. Short-term or continuous infusion of a commercially available amino acid solution to cirrhotic patients caused an increase in methionine, phenylalanine and tyrosine and a decrease in branched chain amino acids. These post-infusion results were similar to the patterns seen in hepatic encephalopathy. In cirrhotic patients, infusion of Fischer solution which contains small quantities of methionine and phenylalanine produced an increase in the concentrations of these 2 amino acids, probably because of impaired utilization by the injured liver. No marked alterations in serum aminograms, however, were observed in cirrhotic patients either immediately after, or 3 h after, the end of the Hep-OU infusion. Reduction of methionine, tyrosine and phenylalanine levels and elevation of the molar ratio of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) were significant. The infusion of Hep-OU to patients with liver cirrhosis or subacute hepatitis resulted in clinical and neurological improvements and the restoration of the molar ratio of branched chain amino acids/aromatic amino acids."} {"id": "PMID:154829", "title": "Low responsiveness of synovial and peripheral blood lymphocytes stimulated by either PHA-P or CON-A in patients with chronic rheumatoid arthritis.", "content": "Lymphocytes were highly purified from synovial fluid and peripheral blood of 10 rheumatoid arthritis patients and assessed for responsiveness to PHA-P and Con-A. In all cases, both synovial and blood lymphocytes showed a marked reduction in response to these mitogens compared with normal blood lymphocytes. The factors responsible for this low T cell responsiveness are discussed.", "contents": "Low responsiveness of synovial and peripheral blood lymphocytes stimulated by either PHA-P or CON-A in patients with chronic rheumatoid arthritis. Lymphocytes were highly purified from synovial fluid and peripheral blood of 10 rheumatoid arthritis patients and assessed for responsiveness to PHA-P and Con-A. In all cases, both synovial and blood lymphocytes showed a marked reduction in response to these mitogens compared with normal blood lymphocytes. The factors responsible for this low T cell responsiveness are discussed."} {"id": "PMID:154830", "title": "The effect of repeated intramuscular gonadotrophin-releasing hormone injections on luteinizing hormone, follicle-stimulating hormone, testosterone, oestrogens, dehydroepiandrosterone and dehydroepiandrosterone sulfate in normal men.", "content": "The endocrine response to three daily intramuscular injections of 500 microgram LH-RH was measured in 9 normal men during a period of 3 days. A marked but declining response in LH was seen in addition to a significant increase in the serum concentration of FSH, testosterone, oestradiol and the urinary excretion of oestrogenic substances. No change could be demonstrated in the DHA, DHAS or cortisol secretion which confirms our previous results of a direct effect of clomiphene on adrenal steroidogenesis.", "contents": "The effect of repeated intramuscular gonadotrophin-releasing hormone injections on luteinizing hormone, follicle-stimulating hormone, testosterone, oestrogens, dehydroepiandrosterone and dehydroepiandrosterone sulfate in normal men. The endocrine response to three daily intramuscular injections of 500 microgram LH-RH was measured in 9 normal men during a period of 3 days. A marked but declining response in LH was seen in addition to a significant increase in the serum concentration of FSH, testosterone, oestradiol and the urinary excretion of oestrogenic substances. No change could be demonstrated in the DHA, DHAS or cortisol secretion which confirms our previous results of a direct effect of clomiphene on adrenal steroidogenesis."} {"id": "PMID:154831", "title": "The athlete's heart.", "content": "In summary, we have discussed the anatomical and physiologic effects of physical training and how they alter the physical examination, thoracic roentgenogram, ECG, and echocardiogram of the athlete. The importance of recognizing these deviations from \"normal\" findings is to avoid considering them evidence of cardiac disease. On the other hand, it is important to exclude cardiovascular disease in those pursuing vigorous athletics because of the potential for sudden cardiac death in those with coronary artery, valvular, or myocardial disease. Unfortunately, the first manifestation of coronary artery disease may be sudden death during athletic performance, a disease not easily detected in asymptomatic individuals. Finally, improper training, excessive trauma, and extreme environmental conditions may contribute to cardiovascular accidents in the competing athlete.", "contents": "The athlete's heart. In summary, we have discussed the anatomical and physiologic effects of physical training and how they alter the physical examination, thoracic roentgenogram, ECG, and echocardiogram of the athlete. The importance of recognizing these deviations from \"normal\" findings is to avoid considering them evidence of cardiac disease. On the other hand, it is important to exclude cardiovascular disease in those pursuing vigorous athletics because of the potential for sudden cardiac death in those with coronary artery, valvular, or myocardial disease. Unfortunately, the first manifestation of coronary artery disease may be sudden death during athletic performance, a disease not easily detected in asymptomatic individuals. Finally, improper training, excessive trauma, and extreme environmental conditions may contribute to cardiovascular accidents in the competing athlete."} {"id": "PMID:154832", "title": "HL-A and hypertrophic cardiomyopathy.", "content": "HL-A antigens were determined in 26 unrelated Japanese patients with hypertrophic cardiomyopathy. Several antigens were more common in patients compared with controls, but statistically significant differences were not evidenced. We also studied two families in which many had a hypertrophic cardiomyopathy. All the affected individuals revealed HL-A-A9 and B7, while none among the unaffected family members had HL-A-B7. Our findings suggest that the HLA-A system may play some role in the pathogenesis of hypertrophic cardiomyopathy with familial occurrence.", "contents": "HL-A and hypertrophic cardiomyopathy. HL-A antigens were determined in 26 unrelated Japanese patients with hypertrophic cardiomyopathy. Several antigens were more common in patients compared with controls, but statistically significant differences were not evidenced. We also studied two families in which many had a hypertrophic cardiomyopathy. All the affected individuals revealed HL-A-A9 and B7, while none among the unaffected family members had HL-A-B7. Our findings suggest that the HLA-A system may play some role in the pathogenesis of hypertrophic cardiomyopathy with familial occurrence."} {"id": "PMID:154833", "title": "Sleep apnea and Q-T interval prolongation--a particularly lethal combination.", "content": "We have discovered a 20-day-old infant who possessed anatomic evidence of chronic hypoxemia with right ventricular hypertrophy and who died in hypoxic hypoxemia with a postmortem PO2 of 4 mm. Hg. Subsequently, and ECG was discovered which had been obtained at one day of age and showed Q-T interval prolongation along with T-wave alternation. We believe this case to be one of the first to substantiate the mechanism for SIDS as proposed by Schwartz, 26 with hypoxia acting synergistically with a prolonged Q-T interval causing sudden unexpected death in this infant--providing a link between cardiac and respiratory mechanisms of death.", "contents": "Sleep apnea and Q-T interval prolongation--a particularly lethal combination. We have discovered a 20-day-old infant who possessed anatomic evidence of chronic hypoxemia with right ventricular hypertrophy and who died in hypoxic hypoxemia with a postmortem PO2 of 4 mm. Hg. Subsequently, and ECG was discovered which had been obtained at one day of age and showed Q-T interval prolongation along with T-wave alternation. We believe this case to be one of the first to substantiate the mechanism for SIDS as proposed by Schwartz, 26 with hypoxia acting synergistically with a prolonged Q-T interval causing sudden unexpected death in this infant--providing a link between cardiac and respiratory mechanisms of death."} {"id": "PMID:154834", "title": "Post-traumatic coronary occlusion and early left ventricular aneurysm.", "content": "A case of post-traumatic coronary occlusion is presented. A 38-year-old sustained a blunt chest trauma with secondary transmural infarct and early evolution toward a huge left ventricular aneurysm. Coronary arteriography showed complete occlusion to the left anterior descending coronary artery.", "contents": "Post-traumatic coronary occlusion and early left ventricular aneurysm. A case of post-traumatic coronary occlusion is presented. A 38-year-old sustained a blunt chest trauma with secondary transmural infarct and early evolution toward a huge left ventricular aneurysm. Coronary arteriography showed complete occlusion to the left anterior descending coronary artery."} {"id": "PMID:154837", "title": "Studies of 16-androstenes in an infant with virilizing adrenal carcinoma.", "content": "An 18-month-old girl with virilization was found to have an encapsulated right adrenal carcinoma (2 x3 cm) with great variation in nuclear size, frequent mitoses, and possible blood vessel invasion. Preoperative urinary excretions of 17-ketosteroids, androsterone, etiocholanolone, dehydroepiandrosterone, testosterone, pregnanetriol, 3alpha-androstenol, and 3 beta-androstadienol were elevated; all showed a noticeable decrease postoperatively. Cortisol acetate, given preoperatively, produced a definite decrease in the urinary excretion of 17-ketosteroids and dehydroepiandrosterone; administration of corticotropin resulted in an increase in levels of urinary 17-ketosteroids, 17-hydroxycorticosteroids, and pregnanetriol. Urinary testosterone and 3beta-androstadienol may have diagnostic value since neither was suppressed by cortisol therapy. The behavior of both 3alpha-androstenol and 3beta-androstadienol in this study suggests that they are of adrenal origin.", "contents": "Studies of 16-androstenes in an infant with virilizing adrenal carcinoma. An 18-month-old girl with virilization was found to have an encapsulated right adrenal carcinoma (2 x3 cm) with great variation in nuclear size, frequent mitoses, and possible blood vessel invasion. Preoperative urinary excretions of 17-ketosteroids, androsterone, etiocholanolone, dehydroepiandrosterone, testosterone, pregnanetriol, 3alpha-androstenol, and 3 beta-androstadienol were elevated; all showed a noticeable decrease postoperatively. Cortisol acetate, given preoperatively, produced a definite decrease in the urinary excretion of 17-ketosteroids and dehydroepiandrosterone; administration of corticotropin resulted in an increase in levels of urinary 17-ketosteroids, 17-hydroxycorticosteroids, and pregnanetriol. Urinary testosterone and 3beta-androstadienol may have diagnostic value since neither was suppressed by cortisol therapy. The behavior of both 3alpha-androstenol and 3beta-androstadienol in this study suggests that they are of adrenal origin."} {"id": "PMID:154840", "title": "Fate of circulating immune complexes in infective endocarditis.", "content": "To examine the role of circulating immune complexes (CIC) in infective endocarditis, we studied 64 patients with infective endocarditis for the presence of CIC by the polyethylene-glycol (PEG)-precipitation test and the Clq binding test. This study was repeated during the course of the disease in 23 patients. CIC were found in 84 per cent of patients (66 per cent with acute infective endocarditis, 89 per cent with subacute infective endocarditis) during the active phase of the disease. Higer PEG precipitates were associated with typical cutaneous signs, cryoglobulins and nonstreptococcic culture-positive infective endocarditis. Under appropriate antibiotic treatment, the PEG precipitate levels of 17 patients fell within 1 month to the normal range, with a concomitant drop in cryoglobulinemia and rheumatoid factor. Conversely, uncontrolled sepsis always (six of six) yielded a rising level of CIC. These findings support the hypothesis that CIC may be important in the pathogenesis of peripheral lesions in infective endocarditis.", "contents": "Fate of circulating immune complexes in infective endocarditis. To examine the role of circulating immune complexes (CIC) in infective endocarditis, we studied 64 patients with infective endocarditis for the presence of CIC by the polyethylene-glycol (PEG)-precipitation test and the Clq binding test. This study was repeated during the course of the disease in 23 patients. CIC were found in 84 per cent of patients (66 per cent with acute infective endocarditis, 89 per cent with subacute infective endocarditis) during the active phase of the disease. Higer PEG precipitates were associated with typical cutaneous signs, cryoglobulins and nonstreptococcic culture-positive infective endocarditis. Under appropriate antibiotic treatment, the PEG precipitate levels of 17 patients fell within 1 month to the normal range, with a concomitant drop in cryoglobulinemia and rheumatoid factor. Conversely, uncontrolled sepsis always (six of six) yielded a rising level of CIC. These findings support the hypothesis that CIC may be important in the pathogenesis of peripheral lesions in infective endocarditis."} {"id": "PMID:154843", "title": "Verbal operants in mothers' speech to nonretarded and Down's syndrome children matched for linguistic level.", "content": "Verbal response classes produced by mothers speaking to 21 nonretarded children were compared with those of mothers speaking to 21 Down's syndrome children matched with them on mean length of utterance. As mean length of utterance increased, total verbal response classes increased for both groups of mothers and children. Nonretarded children and their mothers produced more echoics; retarded children and their mothers produced more intraverbals. The implications of these findings were discussed in relation to previous research and the teaching of language.", "contents": "Verbal operants in mothers' speech to nonretarded and Down's syndrome children matched for linguistic level. Verbal response classes produced by mothers speaking to 21 nonretarded children were compared with those of mothers speaking to 21 Down's syndrome children matched with them on mean length of utterance. As mean length of utterance increased, total verbal response classes increased for both groups of mothers and children. Nonretarded children and their mothers produced more echoics; retarded children and their mothers produced more intraverbals. The implications of these findings were discussed in relation to previous research and the teaching of language."} {"id": "PMID:154844", "title": "Visual handicaps of mentally handicapped people.", "content": "Recent literature concerning visual handicaps of mentally handicapped people was reviewed. Topic areas considered were etiology and epidemiology, visual acuity, color vision, and educational techniques. The material considered indicated that a large proportion of mentally handicapped people are affected by some form of visual handicap and the extent to which further specialization of care and training techniques is required in order to limit the extra disadvantages imposed by such defects.", "contents": "Visual handicaps of mentally handicapped people. Recent literature concerning visual handicaps of mentally handicapped people was reviewed. Topic areas considered were etiology and epidemiology, visual acuity, color vision, and educational techniques. The material considered indicated that a large proportion of mentally handicapped people are affected by some form of visual handicap and the extent to which further specialization of care and training techniques is required in order to limit the extra disadvantages imposed by such defects."} {"id": "PMID:154845", "title": "Hypertrophic cardiomyopathy in the dog.", "content": "Clinical and necropsy findings in 10 dogs with a spontaneous primary hypertrophic cardiomyopathy are described. Each dog had marked cardiac hypertrophy, and 8 dogs had disproportionate thickening of the ventricular septum with respect to the left ventricular free wall (compared with dogs with normal hearts or with cardiac hypertrophy due to acquired or congenital heart disease). Septal:free wall thickness ratios in the 10 dogs ranged from 1.1 to 1.5; 6 had ratios greater than or equal to 1.3. However, marked cardiac muscle cell disorganization in the ventricular septum, characteristic of patients with hypertrophic cardiomyopathy, was present in only 2 of the 10 dogs. Death occurred most commonly while the dogs were under anesthesia during the course of operative procedures (5 dogs) or suddenly and unexpectedly in animals without previous symptomatic manifestations of cardiac disease (3 dogs). Four dogs had clinical signs of congestive heart failure, including 2 with marked cardiac decompensation. In addition, 2 of these 4 dogs with heart failure and 1 dog without previous symptoms (that died during a noncardiac operation) manifested complete heart block. It is conceivable that dogs with spontaneous hypertrophic cardiomyopathy may prove useful in the future investigations of the clinical, hemodynamic, and pathologic features of this disease in humans.", "contents": "Hypertrophic cardiomyopathy in the dog. Clinical and necropsy findings in 10 dogs with a spontaneous primary hypertrophic cardiomyopathy are described. Each dog had marked cardiac hypertrophy, and 8 dogs had disproportionate thickening of the ventricular septum with respect to the left ventricular free wall (compared with dogs with normal hearts or with cardiac hypertrophy due to acquired or congenital heart disease). Septal:free wall thickness ratios in the 10 dogs ranged from 1.1 to 1.5; 6 had ratios greater than or equal to 1.3. However, marked cardiac muscle cell disorganization in the ventricular septum, characteristic of patients with hypertrophic cardiomyopathy, was present in only 2 of the 10 dogs. Death occurred most commonly while the dogs were under anesthesia during the course of operative procedures (5 dogs) or suddenly and unexpectedly in animals without previous symptomatic manifestations of cardiac disease (3 dogs). Four dogs had clinical signs of congestive heart failure, including 2 with marked cardiac decompensation. In addition, 2 of these 4 dogs with heart failure and 1 dog without previous symptoms (that died during a noncardiac operation) manifested complete heart block. It is conceivable that dogs with spontaneous hypertrophic cardiomyopathy may prove useful in the future investigations of the clinical, hemodynamic, and pathologic features of this disease in humans."} {"id": "PMID:154846", "title": "Effect of low fibrinogen concentrations on the rheology of human blood in vitro.", "content": "The influence of low concentrations of fibrinogen on the rheology of normal human blood was investigated with an instrument that permitted simultaneous determination of viscosity and the state of red blood cell aggregation and deformation. Fibrinogen, in concentrations of 9-82 mg/100 ml, decreased blood viscosity at all shear rates below the value obtained with red blood cells suspended in serum. At concentrations above 116 mg/100 ml viscosity was increased. Aggregate formation increased progressively as the fibrinogen concentration increased, necessitating higher dispersing shear rates. The deformation and alignment of the red cells, occurring at a shear rate of 230 s-1, was facilitated by low concentrations. The effect of fibrinogen on low-shear viscosity is explained by the formation of different kinds of aggregates. At low concentrations, the aggregates consist of only few cells forming spherelike particles displaying hemodynamic properties better than those of the single discoid cells. At normal or high concentrations big rodlike aggregates occur and increase resistance to flow.", "contents": "Effect of low fibrinogen concentrations on the rheology of human blood in vitro. The influence of low concentrations of fibrinogen on the rheology of normal human blood was investigated with an instrument that permitted simultaneous determination of viscosity and the state of red blood cell aggregation and deformation. Fibrinogen, in concentrations of 9-82 mg/100 ml, decreased blood viscosity at all shear rates below the value obtained with red blood cells suspended in serum. At concentrations above 116 mg/100 ml viscosity was increased. Aggregate formation increased progressively as the fibrinogen concentration increased, necessitating higher dispersing shear rates. The deformation and alignment of the red cells, occurring at a shear rate of 230 s-1, was facilitated by low concentrations. The effect of fibrinogen on low-shear viscosity is explained by the formation of different kinds of aggregates. At low concentrations, the aggregates consist of only few cells forming spherelike particles displaying hemodynamic properties better than those of the single discoid cells. At normal or high concentrations big rodlike aggregates occur and increase resistance to flow."} {"id": "PMID:154847", "title": "Fiber orientation in hypertrophied canine left ventricle.", "content": "Myocardial fiber orientation was examined in transmural specimens obtained at the maximum diameter of the left ventricle from five dogs with pressure-overload hypertrophy produced by aortic stenosis, six dogs with volume-overload hypertrophy due to an arteriovenous fistula, and six exercise-hypertrophied greyhounds trained for racing. Hearts arrested in diastole were fixed in situ while the operating end-diastolic pressure was maintained. Fiber orientation changed smoothly from about +60 degrees (with respect to the equator) at the endocardium to about -69 degrees at the epicardium. The majority of fibers near the midwall were oriented circumferentially. These findings are quite similar to those previously reported for normal dogs. In comparison to normals, the left ventricles from dogs with pressure-overload had an increase in longitudinally oriented fibers, i.e. fiber angles between -67.5 degrees and -90 degrees and between +67.5 degrees and +90 degrees; these fibers comprised 10.4 +/- 1.8% of the total fibers in dogs with aortic stenosis vs. 2.9 +/- 1.8% of total fibers in normal dogs (P less than 0.001). Neither the dogs with volume-overload hypertrophy nor exercise-trained animals were significantly different from normals.", "contents": "Fiber orientation in hypertrophied canine left ventricle. Myocardial fiber orientation was examined in transmural specimens obtained at the maximum diameter of the left ventricle from five dogs with pressure-overload hypertrophy produced by aortic stenosis, six dogs with volume-overload hypertrophy due to an arteriovenous fistula, and six exercise-hypertrophied greyhounds trained for racing. Hearts arrested in diastole were fixed in situ while the operating end-diastolic pressure was maintained. Fiber orientation changed smoothly from about +60 degrees (with respect to the equator) at the endocardium to about -69 degrees at the epicardium. The majority of fibers near the midwall were oriented circumferentially. These findings are quite similar to those previously reported for normal dogs. In comparison to normals, the left ventricles from dogs with pressure-overload had an increase in longitudinally oriented fibers, i.e. fiber angles between -67.5 degrees and -90 degrees and between +67.5 degrees and +90 degrees; these fibers comprised 10.4 +/- 1.8% of the total fibers in dogs with aortic stenosis vs. 2.9 +/- 1.8% of total fibers in normal dogs (P less than 0.001). Neither the dogs with volume-overload hypertrophy nor exercise-trained animals were significantly different from normals."} {"id": "PMID:154848", "title": "Effect of implant duration on in vivo sensitivity of electromagnetic flow transducers.", "content": "Twenty-three electromagnetic flow transducers with lumen diameters of 3.5-6.0 mm were implanted in rhesus monkeys and baboonss for 12 h to 120 days. Each flow transducer was calibrated 1) in vitro on dialysis tubing with saline before implantation, 2) in vivo the last day of the implant period, and 3) again in vitro after the flow transducer was recovered. Three other flow transducers were implanted on femoral arteries of baboon just central to an arteriovenous Silastic shunt, and were calibrated in vivo daily for 23-47 days. In vitro sensitivity was not affected by implant durations of up to 120 days. In vivo sensitivity fluctuated unpredictably for the first 3-4 wk of implant, after which it followed a systematic course that depended on the lumen size. In vivo sensitivity at any time during implant (after the initial period) could be accurately predicted by knowing either the in vitro sensitivity or the terminal in vivo sensitivity.", "contents": "Effect of implant duration on in vivo sensitivity of electromagnetic flow transducers. Twenty-three electromagnetic flow transducers with lumen diameters of 3.5-6.0 mm were implanted in rhesus monkeys and baboonss for 12 h to 120 days. Each flow transducer was calibrated 1) in vitro on dialysis tubing with saline before implantation, 2) in vivo the last day of the implant period, and 3) again in vitro after the flow transducer was recovered. Three other flow transducers were implanted on femoral arteries of baboon just central to an arteriovenous Silastic shunt, and were calibrated in vivo daily for 23-47 days. In vitro sensitivity was not affected by implant durations of up to 120 days. In vivo sensitivity fluctuated unpredictably for the first 3-4 wk of implant, after which it followed a systematic course that depended on the lumen size. In vivo sensitivity at any time during implant (after the initial period) could be accurately predicted by knowing either the in vitro sensitivity or the terminal in vivo sensitivity."} {"id": "PMID:154851", "title": "Coverage of exposed vascular conduits.", "content": "When a vascular conduit becomes exposed, it is generally thought that if it is not already infected, it will soon become so. The most comprehensive treatment would be removal of the prosthesis, debridement of the wound, and extraanatomic bypass. Occasionally, however, extraanatomic bypass cannot be done. In such cases, local measures, such as skin grafting or skin flap coverage, may be used. Our two cases illustrate that these procedures can, on occasion, provide long-term coverage of exposed vascular conduits.", "contents": "Coverage of exposed vascular conduits. When a vascular conduit becomes exposed, it is generally thought that if it is not already infected, it will soon become so. The most comprehensive treatment would be removal of the prosthesis, debridement of the wound, and extraanatomic bypass. Occasionally, however, extraanatomic bypass cannot be done. In such cases, local measures, such as skin grafting or skin flap coverage, may be used. Our two cases illustrate that these procedures can, on occasion, provide long-term coverage of exposed vascular conduits."} {"id": "PMID:154854", "title": "Calcium and glycoprotein metabolism as correlates for ethanol preference and sensitivity.", "content": "Enzyme markers associated with calcium and glycoprotein metabolism may be correlated with the sensitivity and preference to alcohol in rodent strains.", "contents": "Calcium and glycoprotein metabolism as correlates for ethanol preference and sensitivity. Enzyme markers associated with calcium and glycoprotein metabolism may be correlated with the sensitivity and preference to alcohol in rodent strains."} {"id": "PMID:154855", "title": "[Distribution of 35S labeled sulfated mucopolysaccharides in the recipient eye after corneal allografting. Experimental studies in rabbits].", "content": "The release of 35S labeled corneal glycoprotein from an allogenic interlamellar corneal graft was studied in randomly selected rabbits. Simultaneously, the uptake of 35S by the recipient animal was investigated. These changes followed for a period of 80 h indicate that there is a constant 35S release fromthe donor cornea and that it is the recipient cornea which takes up the major part of the 35S from the donor. The iris, choroid, and sclera of the recipient also take up a certain percentage of the donor's 35S while the aqueous humor, the optic nerve, and the local lymph nodes take up only minimal amounts.", "contents": "[Distribution of 35S labeled sulfated mucopolysaccharides in the recipient eye after corneal allografting. Experimental studies in rabbits]. The release of 35S labeled corneal glycoprotein from an allogenic interlamellar corneal graft was studied in randomly selected rabbits. Simultaneously, the uptake of 35S by the recipient animal was investigated. These changes followed for a period of 80 h indicate that there is a constant 35S release fromthe donor cornea and that it is the recipient cornea which takes up the major part of the 35S from the donor. The iris, choroid, and sclera of the recipient also take up a certain percentage of the donor's 35S while the aqueous humor, the optic nerve, and the local lymph nodes take up only minimal amounts."} {"id": "PMID:154857", "title": "Histochemical characteristics of the masseter and temporalis muscles of the rhesus monkey (Macaca mulatta).", "content": "The histochemical characteristics, cross-sectional area and capillary of the skeletal muscle fibers of the anterior and posterior regions of the superficial masseter and the temporalis muscles are described for juvenile and adult rhesus monkeys of both sexes. Slow twitch fatigue resistant (S), fast twitch fatigue resistant (FR) and fast twitch fatigable (FF) fibers were found in varying proportions throughout the muscles; however some fibers with an intermediate myofibrillar ATPase activity were observed in the anterior masseter. No significant differences for any of the variables were found between male and female juveniles for a specific muscle sample site. However, considerable variation was found between juvenile and adult and between adult male and female monkeys in the percentages of different fiber types and the cross-sectional area of fibers in specific regions of the superficial masseter and temporalis muscles. We conclude from these observations that significant differences in function exist both within and between the different masticatory muscles of rhesus monkeys. Functional differences may result from the pronounced sexual dimorphism evident in the dentofacial complex of the rhesus monkey.", "contents": "Histochemical characteristics of the masseter and temporalis muscles of the rhesus monkey (Macaca mulatta). The histochemical characteristics, cross-sectional area and capillary of the skeletal muscle fibers of the anterior and posterior regions of the superficial masseter and the temporalis muscles are described for juvenile and adult rhesus monkeys of both sexes. Slow twitch fatigue resistant (S), fast twitch fatigue resistant (FR) and fast twitch fatigable (FF) fibers were found in varying proportions throughout the muscles; however some fibers with an intermediate myofibrillar ATPase activity were observed in the anterior masseter. No significant differences for any of the variables were found between male and female juveniles for a specific muscle sample site. However, considerable variation was found between juvenile and adult and between adult male and female monkeys in the percentages of different fiber types and the cross-sectional area of fibers in specific regions of the superficial masseter and temporalis muscles. We conclude from these observations that significant differences in function exist both within and between the different masticatory muscles of rhesus monkeys. Functional differences may result from the pronounced sexual dimorphism evident in the dentofacial complex of the rhesus monkey."} {"id": "PMID:154858", "title": "The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat.", "content": "Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slow bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-defined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.", "contents": "The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat. Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slow bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-defined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration."} {"id": "PMID:154859", "title": "Septal aneurysm and right ventricular obstruction: a case report.", "content": "A 32-year-old man with a history of ventricular septal defect presented with systolic and diastolic murmurs and vectocardiographic evidence of right ventricular hypertrophy. Echocardiography demonstrated a prominent systolic bulging of the interventricular septum into the right ventricle. Left ventricular angiograms indicated that the ultrasonic abnormality was based on an aneurysm of the membranous septum which produced a 35 mm Hg gradient within the right ventricle. After plication of this aneurysm, murmur and abnormal septal protrusion were not recorded.", "contents": "Septal aneurysm and right ventricular obstruction: a case report. A 32-year-old man with a history of ventricular septal defect presented with systolic and diastolic murmurs and vectocardiographic evidence of right ventricular hypertrophy. Echocardiography demonstrated a prominent systolic bulging of the interventricular septum into the right ventricle. Left ventricular angiograms indicated that the ultrasonic abnormality was based on an aneurysm of the membranous septum which produced a 35 mm Hg gradient within the right ventricle. After plication of this aneurysm, murmur and abnormal septal protrusion were not recorded."} {"id": "PMID:154860", "title": "\"Steroid-phobia\" in asthma management.", "content": "Excellent clinical results were obtained in 85 patients with chronic asthma who took corticosteroids (mostly triamcinolone) on a long-term basis for periods varying from one to 26 years. There was a minimum of side-effects, none serious; the most discomforting were ecchymosis and a tendency to easy bruising. The results of this and previous studies have convinced the author that corticosteroids, if judiciously used, are the most valuable adjunct we have in the treatment of acute and chronic asthma.", "contents": "\"Steroid-phobia\" in asthma management. Excellent clinical results were obtained in 85 patients with chronic asthma who took corticosteroids (mostly triamcinolone) on a long-term basis for periods varying from one to 26 years. There was a minimum of side-effects, none serious; the most discomforting were ecchymosis and a tendency to easy bruising. The results of this and previous studies have convinced the author that corticosteroids, if judiciously used, are the most valuable adjunct we have in the treatment of acute and chronic asthma."} {"id": "PMID:154870", "title": "Newly acquired left bundle-branch block: the Framingham study.", "content": "The clinical implications of newly acquired left bundle-branch block (LBBB) were examined prospectively in the Framingham Study population. During 18 years of observation 55 people developed LBBB. The mean age at the onset of LBBB was 62; LBBB occurred largely in people with antecedent hypertension, cardiac enlargement, coronary heart disease, or a combination of these. Coincident with or subsequent to the onset of LBBB, 48% developed clinical coronary disease or congestive failure for the first time. Throughout the entire period of observation only 11% remained free of clinically apparent cardiovascular abnormalities. Within 10 years of the onset of LBBB, 50% had died from cardiovascular diseases. In men, the appearance of LBBB contributed independently to an increased risk of cardiovascular disease mortality. Comparison with age- and sex-matched control subjects free from LBBB confirmed that in the general adult population, newly acquired LBBB is most often a hallmark of advanced hypertensive or ischemic heart disease, or both.", "contents": "Newly acquired left bundle-branch block: the Framingham study. The clinical implications of newly acquired left bundle-branch block (LBBB) were examined prospectively in the Framingham Study population. During 18 years of observation 55 people developed LBBB. The mean age at the onset of LBBB was 62; LBBB occurred largely in people with antecedent hypertension, cardiac enlargement, coronary heart disease, or a combination of these. Coincident with or subsequent to the onset of LBBB, 48% developed clinical coronary disease or congestive failure for the first time. Throughout the entire period of observation only 11% remained free of clinically apparent cardiovascular abnormalities. Within 10 years of the onset of LBBB, 50% had died from cardiovascular diseases. In men, the appearance of LBBB contributed independently to an increased risk of cardiovascular disease mortality. Comparison with age- and sex-matched control subjects free from LBBB confirmed that in the general adult population, newly acquired LBBB is most often a hallmark of advanced hypertensive or ischemic heart disease, or both."} {"id": "PMID:154872", "title": "[Clinical evaluation of a topical ethyl lactate treatment of acne vulgaris (author's transl)].", "content": "The efficacy of a lotion containing 10 p. 100 ethyl lactate was evaluated in a double-blind clinical trail during 8 weeks. Test subjects were 45 male and female patients with polymorphous juvenile acne. They were divided into three groups and received the following treatments: Group A: oral antibiotic + topical placebo lotion. Group B: oral antibiotic + topical ethyl lactate lotion. Group C: topical ethyl lactate lotion only. The lotions were applied twice daily with a swab of cotton-wool. The antibiotic doses (tetracycline hydrochloride) were decreased as the trial progressed. Patients were examined before the trial, then after 1, 2, 4, 6 and 8 weeks. At each visit, comedones, microcysts, pustules and nodules were counted on a skin surface of 9 cm2. Colour photographs were taken before and at the end of the trial and served for counting inflammatory lesions. Also, at each visit, skin lipids were sampled and analysed by I. R. spectrophotometry in order to asses the effect of the treatments on the free fatty acid/triglyceride ratio. The treatments showed similar effectiveness as regards comedones and microcysts, but only treatments A and B succeeded in reducing the number of inflamed lesions. With respect to the latter, the combined treatment B (oral antibiotic + topical ethyl lactate lotion) was more effective than treatment A (oral antibiotic + topical placebo); both treatments were more effective than treatment C (topical ethyl lactate lotion only). At the end of the trial, all three groups of patients showed significant overall improvement, but acne scores (total number of lesions) did not differ significantly between treatments. When comparing these results with literature data concerning the effects of vitamin A acid and benzoyl peroxide, it appears that ethyl lactate is slightly less effective for topical treatment of acne than vitamin A acid, but slightly more effective than benzoyl peroxide. It should be underlined that ethyl lactate is well tolerated by the skin. Analysis of sebum samples failed to yield evidence of a decrease in the free fatty acid/triglyceride ratio in skin lipids of the patients irrespective of the treatment applied.", "contents": "[Clinical evaluation of a topical ethyl lactate treatment of acne vulgaris (author's transl)]. The efficacy of a lotion containing 10 p. 100 ethyl lactate was evaluated in a double-blind clinical trail during 8 weeks. Test subjects were 45 male and female patients with polymorphous juvenile acne. They were divided into three groups and received the following treatments: Group A: oral antibiotic + topical placebo lotion. Group B: oral antibiotic + topical ethyl lactate lotion. Group C: topical ethyl lactate lotion only. The lotions were applied twice daily with a swab of cotton-wool. The antibiotic doses (tetracycline hydrochloride) were decreased as the trial progressed. Patients were examined before the trial, then after 1, 2, 4, 6 and 8 weeks. At each visit, comedones, microcysts, pustules and nodules were counted on a skin surface of 9 cm2. Colour photographs were taken before and at the end of the trial and served for counting inflammatory lesions. Also, at each visit, skin lipids were sampled and analysed by I. R. spectrophotometry in order to asses the effect of the treatments on the free fatty acid/triglyceride ratio. The treatments showed similar effectiveness as regards comedones and microcysts, but only treatments A and B succeeded in reducing the number of inflamed lesions. With respect to the latter, the combined treatment B (oral antibiotic + topical ethyl lactate lotion) was more effective than treatment A (oral antibiotic + topical placebo); both treatments were more effective than treatment C (topical ethyl lactate lotion only). At the end of the trial, all three groups of patients showed significant overall improvement, but acne scores (total number of lesions) did not differ significantly between treatments. When comparing these results with literature data concerning the effects of vitamin A acid and benzoyl peroxide, it appears that ethyl lactate is slightly less effective for topical treatment of acne than vitamin A acid, but slightly more effective than benzoyl peroxide. It should be underlined that ethyl lactate is well tolerated by the skin. Analysis of sebum samples failed to yield evidence of a decrease in the free fatty acid/triglyceride ratio in skin lipids of the patients irrespective of the treatment applied."} {"id": "PMID:154873", "title": "[Effect of surface-active antiseptics on plasmid transduction of drug resistance and the transducing bacteriophages of staphylococci].", "content": "Anionic surface active substances (SAS), such as sodium alkylsulfates, iodonate, sulfanol NP-3 used in subbacteriostatic concentrations lowered at least 100 times the intensity of the erythromycin resistance plasmid in vitro on mixed cultivation of the staphylococcal cells of the donor (strain 8325/11 de) and the recipient (strain 825-1). The cationic SAS, i. e. roc cal, chlorhexidine had no such capacity. The above anionic and cationic SAS had an antiphage effect with respect to the transducing staphylococcal bacteriophages of the serological group B (80, 85, 52A, 53). Such an effect (on the example of sodium alkylsulfates) increased with prolongation of the alkyl radical from C8 to C14. A decrease in the transduction intensity of the erythromycin resistant plasmid in staphylococci was observed in the presence of the anionic SAS either possessing (alkylsulfates, iodonate) or not (sulfonol NP-3) the antiphage activity.", "contents": "[Effect of surface-active antiseptics on plasmid transduction of drug resistance and the transducing bacteriophages of staphylococci]. Anionic surface active substances (SAS), such as sodium alkylsulfates, iodonate, sulfanol NP-3 used in subbacteriostatic concentrations lowered at least 100 times the intensity of the erythromycin resistance plasmid in vitro on mixed cultivation of the staphylococcal cells of the donor (strain 8325/11 de) and the recipient (strain 825-1). The cationic SAS, i. e. roc cal, chlorhexidine had no such capacity. The above anionic and cationic SAS had an antiphage effect with respect to the transducing staphylococcal bacteriophages of the serological group B (80, 85, 52A, 53). Such an effect (on the example of sodium alkylsulfates) increased with prolongation of the alkyl radical from C8 to C14. A decrease in the transduction intensity of the erythromycin resistant plasmid in staphylococci was observed in the presence of the anionic SAS either possessing (alkylsulfates, iodonate) or not (sulfonol NP-3) the antiphage activity."} {"id": "PMID:154874", "title": "Methicillin-resistant strains of Staphylococcus aureus phage type 92.", "content": "Methicillin-resistant (Mec(r)) strains of Staphylococcus aureus received for phage typing from several hospitals in New York City were resistant to the international set of typing phages but susceptible to experimental phage 92. Subsequently, strains of type 92 were detected in two outbreaks with Mec(r) strains in two other locations in the United States. In all instances, type 92 was predominant among the Mec(r) strains isolated in each hospital. With the exception of one strain, the methicillin resistance of the Mec(r) strains investigated was homogeneous. In most instances, isolates from the same hospital were closely similar in their antibiotic resistance patterns. The strains isolated in New York City could be divided into three groups by the host range of their lysogenic phages and by antigenic structure. Transduction experiments indicated that the transfer of chromosomal tetracycline resistance from Mec(r) strains into a strain susceptible to several international typing phages renders the latter nontypable. However, the acceptor strain remains susceptible to experimental phages 92 and 88. Transduction of methicillin resistance had no effect on the phage susceptibility of the acceptor strain. It is possible that the presence of chromosomal tetracycline resistance is a determining factor in the phage susceptibility of Mec(r) strains isolated in New York City.", "contents": "Methicillin-resistant strains of Staphylococcus aureus phage type 92. Methicillin-resistant (Mec(r)) strains of Staphylococcus aureus received for phage typing from several hospitals in New York City were resistant to the international set of typing phages but susceptible to experimental phage 92. Subsequently, strains of type 92 were detected in two outbreaks with Mec(r) strains in two other locations in the United States. In all instances, type 92 was predominant among the Mec(r) strains isolated in each hospital. With the exception of one strain, the methicillin resistance of the Mec(r) strains investigated was homogeneous. In most instances, isolates from the same hospital were closely similar in their antibiotic resistance patterns. The strains isolated in New York City could be divided into three groups by the host range of their lysogenic phages and by antigenic structure. Transduction experiments indicated that the transfer of chromosomal tetracycline resistance from Mec(r) strains into a strain susceptible to several international typing phages renders the latter nontypable. However, the acceptor strain remains susceptible to experimental phages 92 and 88. Transduction of methicillin resistance had no effect on the phage susceptibility of the acceptor strain. It is possible that the presence of chromosomal tetracycline resistance is a determining factor in the phage susceptibility of Mec(r) strains isolated in New York City."} {"id": "PMID:154875", "title": "Thoracoabdominal aortic aneurysms. A review and current status.", "content": "Surgical management of the thoracoabdominal aortic aneurysm is a formidable undertaking. Presently two fairly distinct operative methods are available. The conventional technique, pioneered by Etheredge, involves replacement of the aneurysm with a synthetic graft and then, step by step, revascularization of the abdominal organs with prosthetic side limbs taken from the primary graft. Individual organ ischemic time is limited to that time required for the performance of each distal side limb anastomosis. The second operative method, first described by Crawford, consists of proximal and distal control of the aneurysm, followed by its incision to simultaneously expose the origin of all four major intra-abdominal arteries. Replacement is then rapidly performed with a tubular Dacron graft including anastomosis of these major intra-abdominal arteries to four elliptical graft incisions, from within the aneurysm. Total operating time is reduced at the expense of prolonged organ ischemia. The conventional method allows for step-by-step intraoperative planning and action, and this technique is accordingly recommended to most surgeons, who have had little experience with this unusual lesion. Our recent successful experience with two cases of extensive thoracoabdominal aortic aneurysms is described as well as a discussion of additional measures which may become useful in certain cases to favor a successful outcome. Finally the problem of potential resultant paraplegia is discussed.", "contents": "Thoracoabdominal aortic aneurysms. A review and current status. Surgical management of the thoracoabdominal aortic aneurysm is a formidable undertaking. Presently two fairly distinct operative methods are available. The conventional technique, pioneered by Etheredge, involves replacement of the aneurysm with a synthetic graft and then, step by step, revascularization of the abdominal organs with prosthetic side limbs taken from the primary graft. Individual organ ischemic time is limited to that time required for the performance of each distal side limb anastomosis. The second operative method, first described by Crawford, consists of proximal and distal control of the aneurysm, followed by its incision to simultaneously expose the origin of all four major intra-abdominal arteries. Replacement is then rapidly performed with a tubular Dacron graft including anastomosis of these major intra-abdominal arteries to four elliptical graft incisions, from within the aneurysm. Total operating time is reduced at the expense of prolonged organ ischemia. The conventional method allows for step-by-step intraoperative planning and action, and this technique is accordingly recommended to most surgeons, who have had little experience with this unusual lesion. Our recent successful experience with two cases of extensive thoracoabdominal aortic aneurysms is described as well as a discussion of additional measures which may become useful in certain cases to favor a successful outcome. Finally the problem of potential resultant paraplegia is discussed."} {"id": "PMID:154871", "title": "Dynamic changes of nasal resistance.", "content": "Fifty human subjects were studied and evaluated utilizing posterior rhinomanometry techniques. The main purpose of the investigation was to study the physiologic dynamic range of nasal resistance so that the data might serve as a baseline, not only for evaluation and diagnosis of pathologic states but also for the assessment of nasal responses to various physiologic, drug-induced, or pathologic challenges. Analysis was divided into two parts: first, the evaluation of the average resistance and average change in resistance for each patient, and second, determination of the maximal amount of change to be expected over 15-minute periods in a healthy subject. These studies give the investigator an idea of the magnitude of change that one might expect in normal physiologic situations, based on the 50 subjects that allowed 1,272 observations for justification of the concept of percent change in nasal resistance and not the value of nasal resistance alone. We concluded that the physiologic change in nasal resistance in a normal individual during a 15-minute interval should be less than 53% of the previous observation of nasal resistance. A change greater than 53% suggests a significant change that cannot be attributed to physiologic variability.", "contents": "Dynamic changes of nasal resistance. Fifty human subjects were studied and evaluated utilizing posterior rhinomanometry techniques. The main purpose of the investigation was to study the physiologic dynamic range of nasal resistance so that the data might serve as a baseline, not only for evaluation and diagnosis of pathologic states but also for the assessment of nasal responses to various physiologic, drug-induced, or pathologic challenges. Analysis was divided into two parts: first, the evaluation of the average resistance and average change in resistance for each patient, and second, determination of the maximal amount of change to be expected over 15-minute periods in a healthy subject. These studies give the investigator an idea of the magnitude of change that one might expect in normal physiologic situations, based on the 50 subjects that allowed 1,272 observations for justification of the concept of percent change in nasal resistance and not the value of nasal resistance alone. We concluded that the physiologic change in nasal resistance in a normal individual during a 15-minute interval should be less than 53% of the previous observation of nasal resistance. A change greater than 53% suggests a significant change that cannot be attributed to physiologic variability."} {"id": "PMID:154876", "title": "The value of the electromagnetic flow probe in experimental and clinical microvascular anastomosis.", "content": "The Gould Statham Blood Flowmeter Model SP 2204 has been used to assess microanastomosis in 25 superficial femoral arteries of rabbits. When a pulsatile wave form has been achieved this correlates with a satisfactory anastomosis and vice versa. The digital read out of estimated volume flow past the anastomosis made by this instrument will need further evaluation. We are persisting with the electromagnetic flow probe in the assessment of our clinical microvascular anastomoses at operation.", "contents": "The value of the electromagnetic flow probe in experimental and clinical microvascular anastomosis. The Gould Statham Blood Flowmeter Model SP 2204 has been used to assess microanastomosis in 25 superficial femoral arteries of rabbits. When a pulsatile wave form has been achieved this correlates with a satisfactory anastomosis and vice versa. The digital read out of estimated volume flow past the anastomosis made by this instrument will need further evaluation. We are persisting with the electromagnetic flow probe in the assessment of our clinical microvascular anastomoses at operation."} {"id": "PMID:154878", "title": "Some properties of vacuoles isolated from Neurospora crassa slime variant.", "content": "A method for the isolation of vacuoles based on polybase induced lysis of protoplasts of the cell wall deficient Neurospora crassa slime variant is described. Isolated vacuoles are characterized by 12 to 50 times increased specific activities of several hydrolases as compared with the total homogenate of protoplasts. Total alpha-amino nitrogen, arginine, and polyphosphate are also greatly enriched in these vacuoles. Vacuoles are equipped with a permease for the transport of basic amino acids across the tonoplast.", "contents": "Some properties of vacuoles isolated from Neurospora crassa slime variant. A method for the isolation of vacuoles based on polybase induced lysis of protoplasts of the cell wall deficient Neurospora crassa slime variant is described. Isolated vacuoles are characterized by 12 to 50 times increased specific activities of several hydrolases as compared with the total homogenate of protoplasts. Total alpha-amino nitrogen, arginine, and polyphosphate are also greatly enriched in these vacuoles. Vacuoles are equipped with a permease for the transport of basic amino acids across the tonoplast."} {"id": "PMID:154879", "title": "Determination of intestinal viability by Doppler ultrasound.", "content": "The Doppler ultrasonic flowmeter was used to determine intestinal serosal and mesenteric blood flows in 130 patients who underwent abdominal aortic vascular procedures and in 14 patients who underwent general surgical procedures. Temporary occlusion of the inferior mesenteric artery (IMA) during aortic surgery resulted in the absence or marked diminution of collateral blood flow over the left side of the colon in eight patients. One patient had the flow in the IMA preserved by proper placement of an end-to-side aortofemoral Dacron prosthesis, whereas the other seven patients underwent replantation of the IMA into the Dacron prosthesis. All patients did well postoperatively. In the 14 general surgical patients, intestinal viability and collateral mesenteric blood flows were determined, which demonstrated that the presence of audible arterial blood flow correlated with ultimate bowel viability. We recommend the use of the Doppler ultrasonic flowmeter in abdominal aortic revascularization procedures to determine the need for IMA reconstruction as well as in general surgical procedures where the surgeon desires a more objective assessment of intestinal viability.", "contents": "Determination of intestinal viability by Doppler ultrasound. The Doppler ultrasonic flowmeter was used to determine intestinal serosal and mesenteric blood flows in 130 patients who underwent abdominal aortic vascular procedures and in 14 patients who underwent general surgical procedures. Temporary occlusion of the inferior mesenteric artery (IMA) during aortic surgery resulted in the absence or marked diminution of collateral blood flow over the left side of the colon in eight patients. One patient had the flow in the IMA preserved by proper placement of an end-to-side aortofemoral Dacron prosthesis, whereas the other seven patients underwent replantation of the IMA into the Dacron prosthesis. All patients did well postoperatively. In the 14 general surgical patients, intestinal viability and collateral mesenteric blood flows were determined, which demonstrated that the presence of audible arterial blood flow correlated with ultimate bowel viability. We recommend the use of the Doppler ultrasonic flowmeter in abdominal aortic revascularization procedures to determine the need for IMA reconstruction as well as in general surgical procedures where the surgeon desires a more objective assessment of intestinal viability."} {"id": "PMID:154880", "title": "[Methods of the multivariate statistical analysis of so-called polyetiological diseases using the example of coronary heart disease].", "content": "General characteristics of the multivariate statistical analysis (MSA) is given. Methodical premises and criteria for the selection of an adequate MSA method applicable to pathoanatomic investigations of the epidemiology of multicausal diseases are presented. The experience of using MSA with computors and standard computing programs in studies of coronary arteries aterosclerosis on the materials of 2060 autopsies is described. The combined use of 4 MSA methods: sequential, correlational, regressional, and discriminant permitted to quantitate the contribution of each of the 8 examined risk factors in the development of aterosclerosis. The most important factors were found to be the age, arterial hypertension, and heredity. Occupational hypodynamia and increased fatness were more important in men, whereas diabetes melitus--in women. The registration of this combination of risk factors by MSA methods provides for more reliable prognosis of the likelihood of coronary heart disease with a fatal outcome than prognosis of the degree of coronary aterosclerosis.", "contents": "[Methods of the multivariate statistical analysis of so-called polyetiological diseases using the example of coronary heart disease]. General characteristics of the multivariate statistical analysis (MSA) is given. Methodical premises and criteria for the selection of an adequate MSA method applicable to pathoanatomic investigations of the epidemiology of multicausal diseases are presented. The experience of using MSA with computors and standard computing programs in studies of coronary arteries aterosclerosis on the materials of 2060 autopsies is described. The combined use of 4 MSA methods: sequential, correlational, regressional, and discriminant permitted to quantitate the contribution of each of the 8 examined risk factors in the development of aterosclerosis. The most important factors were found to be the age, arterial hypertension, and heredity. Occupational hypodynamia and increased fatness were more important in men, whereas diabetes melitus--in women. The registration of this combination of risk factors by MSA methods provides for more reliable prognosis of the likelihood of coronary heart disease with a fatal outcome than prognosis of the degree of coronary aterosclerosis."} {"id": "PMID:154881", "title": "Computerized tomography in hereditary nonprogressive chorea.", "content": "A 56-year-old woman had a 50-year history of childhood-onset chorea without progressive neurologic deficit. The patient's father had a lifelong extrapyramidal disorder characterized by a head-nodding tremor and involuntary movements especially evident with anxiety. The computerized tomographic scan was normal, without evidence of cortical or caudate atrophy. The computerized tomographic scan supports the notion of a functional rather than a structural lesion, and may aid in the discrimination of hereditary nonprogressive chorea from more devastating forms of hereditary chorea.", "contents": "Computerized tomography in hereditary nonprogressive chorea. A 56-year-old woman had a 50-year history of childhood-onset chorea without progressive neurologic deficit. The patient's father had a lifelong extrapyramidal disorder characterized by a head-nodding tremor and involuntary movements especially evident with anxiety. The computerized tomographic scan was normal, without evidence of cortical or caudate atrophy. The computerized tomographic scan supports the notion of a functional rather than a structural lesion, and may aid in the discrimination of hereditary nonprogressive chorea from more devastating forms of hereditary chorea."} {"id": "PMID:154885", "title": "The tortuous tube: pregnancy rate following laparoscopy and hydrotubation.", "content": "256 infertile women whose ovulatory and related male fertility factors were normal were investigated by diagnostic laparoscopy and dye hydrotubation. The tubes were objectively classed into 4 groups--normal, patent with macroscopic tubal adhesions, patent with one tortuosity, and patent with multiple tortuosities. The latter group had a highly significant response to the above procedures and 66% were pregnant within 1 year and 81% within 2 years. No significant effect was found in the other 3 groups. This multiple tortuosity group represents the type of tube that significantly responds to treatment inherent in all tubal patency tests. Its pathogenesis and management are discussed.", "contents": "The tortuous tube: pregnancy rate following laparoscopy and hydrotubation. 256 infertile women whose ovulatory and related male fertility factors were normal were investigated by diagnostic laparoscopy and dye hydrotubation. The tubes were objectively classed into 4 groups--normal, patent with macroscopic tubal adhesions, patent with one tortuosity, and patent with multiple tortuosities. The latter group had a highly significant response to the above procedures and 66% were pregnant within 1 year and 81% within 2 years. No significant effect was found in the other 3 groups. This multiple tortuosity group represents the type of tube that significantly responds to treatment inherent in all tubal patency tests. Its pathogenesis and management are discussed."} {"id": "PMID:154887", "title": "Photosensitivity of respiration in Neurospora mitochondria. A protective role for carotenoid.", "content": "1. The effect of visible light on respiratory activity was studied in two strains of Neurospora crassa, one a wild-type strain able to synthesize carotenoid and the other an albino mutant lacking carotenogenic activity. Light had no effect on growth under the conditions studied, but inhibited respiration of hyphal suspensions. the degree of inhibition being dependent on the carotenoid content of the hyphae. 2. In studies of respiration of isolated mitochondria, three types of photosensitive site were detected. These were the flavo-protein dehydrogenases themselves, a site separate from the latter also associated with the dehydrogenase but re-activatable by treatment with a thiol reagent, and the respiratory quinone, ubiquinone. Cytochrome oxidase, previously reported as photosensitive from many sources, was not appreciably affected by light in these preparations. 3. The degree of inactivation of the respiratory quinone was dependent on the amount of carotenoid in the preparation, high concentrations of the pigment in the mitochondrial membranes providing substantial protection against the effect of light. 4. Separation of the inner and outer membranes of mitochondria showed that under conditions where carotenoid appears to protect quinone, significant amounts are found in the inner mitochondrial membrane, oterhwise carotenoid is restricted to the outer membrane.", "contents": "Photosensitivity of respiration in Neurospora mitochondria. A protective role for carotenoid. 1. The effect of visible light on respiratory activity was studied in two strains of Neurospora crassa, one a wild-type strain able to synthesize carotenoid and the other an albino mutant lacking carotenogenic activity. Light had no effect on growth under the conditions studied, but inhibited respiration of hyphal suspensions. the degree of inhibition being dependent on the carotenoid content of the hyphae. 2. In studies of respiration of isolated mitochondria, three types of photosensitive site were detected. These were the flavo-protein dehydrogenases themselves, a site separate from the latter also associated with the dehydrogenase but re-activatable by treatment with a thiol reagent, and the respiratory quinone, ubiquinone. Cytochrome oxidase, previously reported as photosensitive from many sources, was not appreciably affected by light in these preparations. 3. The degree of inactivation of the respiratory quinone was dependent on the amount of carotenoid in the preparation, high concentrations of the pigment in the mitochondrial membranes providing substantial protection against the effect of light. 4. Separation of the inner and outer membranes of mitochondria showed that under conditions where carotenoid appears to protect quinone, significant amounts are found in the inner mitochondrial membrane, oterhwise carotenoid is restricted to the outer membrane."} {"id": "PMID:154888", "title": "A thermodynamic analysis of the interaction between the mitochondrial coupling adenosine triphosphatase and its naturally occurring inhibitor protein.", "content": "1. The naturally occurring ATPase (adenosine triphosphatase)-inhibitor protein, from bovine heart mitochondria, was obtained as a single pure protein. It was not identical with any of the five subunits (alpha-epsilon) of the isolated ATPase, and appeared to be a single polypeptide chain. 2. The inhibitor combined with the ATPase in a 1:1 molar ratio, producing a completely inhibited ATPase molecule. The affinity of the ATPase for its inhibitor is high; the K(d) is of the order of 10(-8)m. 3. The enthalpy of the ATPase-inhibitor complex-formation is positive, the value of K(d) decreasing as the temperature is raised. This suggests that the forces involved are largely hydrophobic in nature. 4. Hydrolysis of a nucleoside triphosphate promoted formation of the ATPase-inhibitor complex, although the equilibrium position was almost unaffected by the rate of hydrolysis. At low salt concentration, less than 200 turnovers of the ATPase suffice for the ATPase to combine with the inhibitor protein. At higher salt concentrations, a larger number of turnovers is required. It is suggested that the inhibitor binds to a form of the ATPase that is produced transiently during hydrolysis. 5. In the presence of 75mm-K(2)SO(4), the rates of association and dissociation are slow enough to allow their kinetics to be studied. Association is first-order in inhibitor concentration, but fractional order in ATPase concentration. Dissociation is first-order in ATPase-inhibitor complex concentration. The temperature coefficients of the ;on' and ;off' processes were also measured. 6. A simple kinetic model for the ATPase-inhibitor interaction is proposed that can be extended to take into account release of inhibitor protein under energized conditions on the membrane. 7. The isolated ATPase is inhibited by preincubation with Mg(2+), reversible by subsequent addition of EDTA, and by ADP, reversible by subsequent addition of ATP. These effects are not found on the membrane-bound ATPase. The mechanism of these effects is discussed.", "contents": "A thermodynamic analysis of the interaction between the mitochondrial coupling adenosine triphosphatase and its naturally occurring inhibitor protein. 1. The naturally occurring ATPase (adenosine triphosphatase)-inhibitor protein, from bovine heart mitochondria, was obtained as a single pure protein. It was not identical with any of the five subunits (alpha-epsilon) of the isolated ATPase, and appeared to be a single polypeptide chain. 2. The inhibitor combined with the ATPase in a 1:1 molar ratio, producing a completely inhibited ATPase molecule. The affinity of the ATPase for its inhibitor is high; the K(d) is of the order of 10(-8)m. 3. The enthalpy of the ATPase-inhibitor complex-formation is positive, the value of K(d) decreasing as the temperature is raised. This suggests that the forces involved are largely hydrophobic in nature. 4. Hydrolysis of a nucleoside triphosphate promoted formation of the ATPase-inhibitor complex, although the equilibrium position was almost unaffected by the rate of hydrolysis. At low salt concentration, less than 200 turnovers of the ATPase suffice for the ATPase to combine with the inhibitor protein. At higher salt concentrations, a larger number of turnovers is required. It is suggested that the inhibitor binds to a form of the ATPase that is produced transiently during hydrolysis. 5. In the presence of 75mm-K(2)SO(4), the rates of association and dissociation are slow enough to allow their kinetics to be studied. Association is first-order in inhibitor concentration, but fractional order in ATPase concentration. Dissociation is first-order in ATPase-inhibitor complex concentration. The temperature coefficients of the ;on' and ;off' processes were also measured. 6. A simple kinetic model for the ATPase-inhibitor interaction is proposed that can be extended to take into account release of inhibitor protein under energized conditions on the membrane. 7. The isolated ATPase is inhibited by preincubation with Mg(2+), reversible by subsequent addition of EDTA, and by ADP, reversible by subsequent addition of ATP. These effects are not found on the membrane-bound ATPase. The mechanism of these effects is discussed."} {"id": "PMID:154893", "title": "Comparative antiinflammatory and bone protective effects of two diphosphonates in adjuvant arthritis.", "content": "The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethane diphosphonate (Cl2MDP) were evaluated in the rat adjuvant model of arthritis to directly compare their ability to inhibit arthritic processes. The results of the experiment indicated that both diphosphonates inhibited osseous changes, pedal inflammation, and the change in body weight gain patterns which are characteristic of this model. The latter effects suggest that diphosphonates may have antinflammatory activity that is not related to their previously known actions on bone. Cl2MDP appeared to be more effective than EHDP in this particular model when all aspects were considered. The relationship of these results to the potential safety of these compounds in clinical situations is discussed.", "contents": "Comparative antiinflammatory and bone protective effects of two diphosphonates in adjuvant arthritis. The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethane diphosphonate (Cl2MDP) were evaluated in the rat adjuvant model of arthritis to directly compare their ability to inhibit arthritic processes. The results of the experiment indicated that both diphosphonates inhibited osseous changes, pedal inflammation, and the change in body weight gain patterns which are characteristic of this model. The latter effects suggest that diphosphonates may have antinflammatory activity that is not related to their previously known actions on bone. Cl2MDP appeared to be more effective than EHDP in this particular model when all aspects were considered. The relationship of these results to the potential safety of these compounds in clinical situations is discussed."} {"id": "PMID:154894", "title": "Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice.", "content": "Young, syngeneic thymocytes and spleen cells were administered to F1 hybrids of New Zealand Black by New Zealand White (NZB/W) mice beginning at 3 weeks of age and were continuted at 2-week intervals for 8 to 9 months. The development of autoimmunity as assessed by measuring the incidence and level of anti-DNA antibody, the degree of renal involvement, and the survival of recipient mice was evaluated and compared to a control group of animals. No significant differences were noted in these parameters in mice receiving cell transfers as compared to the control group. Therefore, in contrast to other reports, these results suggest that the transfer of young thymus or spleen cells into aging NZB/W mice fails to influence immunoregulation and the subsequent development of autoimmunity.", "contents": "Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice. Young, syngeneic thymocytes and spleen cells were administered to F1 hybrids of New Zealand Black by New Zealand White (NZB/W) mice beginning at 3 weeks of age and were continuted at 2-week intervals for 8 to 9 months. The development of autoimmunity as assessed by measuring the incidence and level of anti-DNA antibody, the degree of renal involvement, and the survival of recipient mice was evaluated and compared to a control group of animals. No significant differences were noted in these parameters in mice receiving cell transfers as compared to the control group. Therefore, in contrast to other reports, these results suggest that the transfer of young thymus or spleen cells into aging NZB/W mice fails to influence immunoregulation and the subsequent development of autoimmunity."} {"id": "PMID:154895", "title": "Application of flow cytometry and cell sorting to megakaryocytopoiesis.", "content": "We have employed flow cytometry (FCM) and cell sorting to quantitate and study megakaryocytes in mouse and rat femoral marrow following their 20- to 30-fold concentration by centrifugal elutriation (CE). This enrichment of megakaryocytes permitted the first determination of their DNA-related fluorescence by FCM analysis following DNA staining. Fluorescence distributions of CE-enriched cell fractions following supravital staining with Hoechst 33342 were similar to those following chromomycin A3 staining of ethanol-fixed cells. Microscopic examination of cells sorted onto glass slides on the basis of their DNA-related fluorescence following supravital staining together with specific acetylcholinesterase staining for megakaryocytes indicated that megakaryocytes generally increased in cell size with increasing DNA content. This technologic application represents a significant advance in the study of megakaryocytopoiesis, since the kinetics of either the normal or perturbed population can now be studied rapidly and quantitatively.", "contents": "Application of flow cytometry and cell sorting to megakaryocytopoiesis. We have employed flow cytometry (FCM) and cell sorting to quantitate and study megakaryocytes in mouse and rat femoral marrow following their 20- to 30-fold concentration by centrifugal elutriation (CE). This enrichment of megakaryocytes permitted the first determination of their DNA-related fluorescence by FCM analysis following DNA staining. Fluorescence distributions of CE-enriched cell fractions following supravital staining with Hoechst 33342 were similar to those following chromomycin A3 staining of ethanol-fixed cells. Microscopic examination of cells sorted onto glass slides on the basis of their DNA-related fluorescence following supravital staining together with specific acetylcholinesterase staining for megakaryocytes indicated that megakaryocytes generally increased in cell size with increasing DNA content. This technologic application represents a significant advance in the study of megakaryocytopoiesis, since the kinetics of either the normal or perturbed population can now be studied rapidly and quantitatively."} {"id": "PMID:154913", "title": "Assessment of left-to-right shunt and left ventricular function in isolated ventricular septal defect. Echocardiographic study.", "content": "This echocardiographic study was designed to assess left ventricular function and pulmonary blood flow in ventricular septal defect. Fifty-one patients aged 2 weeks to 21 years were investigated (group 2). Five of 10 operated patients were studied one week after surgical closure of the defect (group 3) and seven 3 to 6 weeks postoperatively (group 4). The control group consisted of 45 normal subjects aged 2 weeks to 21 (group 1). Left atrium/aortic root dimension ratio (LA/Ao) was used to express the pulmonary systemic flow ratio. Left ventricular chamber size was assessed by measurement of left ventricular end-diastolic dimension and volume. The left ventricular mass and the ratio of end-diastolic volume to left ventricular mass were determined to relate the degree of left ventricular hypertrophy to volume overload. Myocardial function was evaluated using ejection phase indices. Ventricular septal thickness, posterior wall thickness, and echocardiographic patterns of septal motion were also studied. The left atrium/aortic root dimension, end-diastolic volume, and left ventricular mass were significantly greater in group 2 patients (P less than 0.05) than in the normal controls. There was a very good correlation between LA/Ao and pulmonary/systemic flow ratio (r = 0.83). Eleven of the group 2 patients showed asymmetric septal hypertrophy (unrelated to shunt size) but left ventricular function as assessed by ejection phase indices appeared unimpaired. Immediately after operation (group 3) there was a deterioration in left ventricular function in 5 patients as shown by reduced ejection fraction, mean velocity of circumferential shortening, and relative changes in minor axis with systole. Septal motion was impaired but returned to normal in 3 to 6 weeks in 7 patients (group 4). Left atrial/aortic root dimension, end-diastolic volume, and left ventricular mass decreased significantly immediately after operation (group 3) but were still raised at 3 to 6 weeks (group 4).", "contents": "Assessment of left-to-right shunt and left ventricular function in isolated ventricular septal defect. Echocardiographic study. This echocardiographic study was designed to assess left ventricular function and pulmonary blood flow in ventricular septal defect. Fifty-one patients aged 2 weeks to 21 years were investigated (group 2). Five of 10 operated patients were studied one week after surgical closure of the defect (group 3) and seven 3 to 6 weeks postoperatively (group 4). The control group consisted of 45 normal subjects aged 2 weeks to 21 (group 1). Left atrium/aortic root dimension ratio (LA/Ao) was used to express the pulmonary systemic flow ratio. Left ventricular chamber size was assessed by measurement of left ventricular end-diastolic dimension and volume. The left ventricular mass and the ratio of end-diastolic volume to left ventricular mass were determined to relate the degree of left ventricular hypertrophy to volume overload. Myocardial function was evaluated using ejection phase indices. Ventricular septal thickness, posterior wall thickness, and echocardiographic patterns of septal motion were also studied. The left atrium/aortic root dimension, end-diastolic volume, and left ventricular mass were significantly greater in group 2 patients (P less than 0.05) than in the normal controls. There was a very good correlation between LA/Ao and pulmonary/systemic flow ratio (r = 0.83). Eleven of the group 2 patients showed asymmetric septal hypertrophy (unrelated to shunt size) but left ventricular function as assessed by ejection phase indices appeared unimpaired. Immediately after operation (group 3) there was a deterioration in left ventricular function in 5 patients as shown by reduced ejection fraction, mean velocity of circumferential shortening, and relative changes in minor axis with systole. Septal motion was impaired but returned to normal in 3 to 6 weeks in 7 patients (group 4). Left atrial/aortic root dimension, end-diastolic volume, and left ventricular mass decreased significantly immediately after operation (group 3) but were still raised at 3 to 6 weeks (group 4)."} {"id": "PMID:154914", "title": "Pre- and postoperative left ventricular contractile function in patients with aortic valve disease.", "content": "In 43 patients left ventricular micromanometry and cineangiography were performed preoperatively and and 20 months after aortic valve replacement. A score of left ventricular functional impairment, derived from 5 to 8 haemodynamic variables, was calculated as: number of pathological indices x 100/total number of determined indices. Preoperatively the score of left ventricular functional impairment amounted to 35 per cent in group 1 (aortic stenosis: n = 19), to 61 per cent in group 2 (combined lesion:n = 15) (P less than 0.05), and to 87 per cent in group 3 (aortic regurgitation: n = 9) (P less than 0.001). In contrast, the functional classification according to the NYHA showed similar impairment in the 3 groups. Postoperatively the score of left ventricular functional impairment decreased significantly in all 3 groups to 10, 16, and 27 per cent, respectively, but the score of group 3 remained raised (P less than 0.05) as compared with that of group 1. The patients with residual left ventricular dysfunction had a higher preoperative left ventricular muscle mass than the patients with normal or near normal postoperative left ventricular function. It is concluded that (1) at similar functional impairment according to the NYHA classification left ventricular contractile function is more severely impaired in aortic regurgitation and in aortic regurgitation + aortic stenosis than in aortic stenosis alone, (2) left ventricular function improves significantly after valve replacement in all three forms of aortic valve disease, (3) residual functional impairment is greater in aortic regurgitation than in aortic stenosis or aortic stenosis + aortic regurgitation, and (4) persistent postoperative left ventricular functional impairment is found in the patients with severe preoperative hypertrophy.", "contents": "Pre- and postoperative left ventricular contractile function in patients with aortic valve disease. In 43 patients left ventricular micromanometry and cineangiography were performed preoperatively and and 20 months after aortic valve replacement. A score of left ventricular functional impairment, derived from 5 to 8 haemodynamic variables, was calculated as: number of pathological indices x 100/total number of determined indices. Preoperatively the score of left ventricular functional impairment amounted to 35 per cent in group 1 (aortic stenosis: n = 19), to 61 per cent in group 2 (combined lesion:n = 15) (P less than 0.05), and to 87 per cent in group 3 (aortic regurgitation: n = 9) (P less than 0.001). In contrast, the functional classification according to the NYHA showed similar impairment in the 3 groups. Postoperatively the score of left ventricular functional impairment decreased significantly in all 3 groups to 10, 16, and 27 per cent, respectively, but the score of group 3 remained raised (P less than 0.05) as compared with that of group 1. The patients with residual left ventricular dysfunction had a higher preoperative left ventricular muscle mass than the patients with normal or near normal postoperative left ventricular function. It is concluded that (1) at similar functional impairment according to the NYHA classification left ventricular contractile function is more severely impaired in aortic regurgitation and in aortic regurgitation + aortic stenosis than in aortic stenosis alone, (2) left ventricular function improves significantly after valve replacement in all three forms of aortic valve disease, (3) residual functional impairment is greater in aortic regurgitation than in aortic stenosis or aortic stenosis + aortic regurgitation, and (4) persistent postoperative left ventricular functional impairment is found in the patients with severe preoperative hypertrophy."} {"id": "PMID:154915", "title": "Nongenetically transmitted disproportionate ventricular septal thickening associated with left ventricular outflow obstruction.", "content": "Clinical, haemodynamic, and morphological features are described in 2 patients with disproportionate ventricular septal thickening, left ventricular outflow obstruction with systolic anterior motion of the anterior mitral leaflet, and either acquired or congenital heart disease. The disproportionate septal thickening in these patients appeared to be secondary to their underlying cardiac disease rather than a manifestation of genetically transmitted hypertrophic cardiomyopathy. One patient with combined aortic and mitral stenosis had severe systolic anterior motion of the anterior mitral leaflet and a residual large systolic pressure gradient between left ventricle and systemic artery after aortic valve replacement. In this patient the systolic anterior motion was evident in the presence of mitral valve stenosis. The other patient with mild aortic stenosis and a previously repaired coarctation of the aorta also had mild systolic anterior motion and a small subaortic systolic pressure gradient. Hence, these 2 patients demonstrate that disproportionate septal thickening secondary to acquired or congenital heart disease may be associated with left ventricular outflow obstruction and systolic anterior motion of the anterior mitral leaflet.", "contents": "Nongenetically transmitted disproportionate ventricular septal thickening associated with left ventricular outflow obstruction. Clinical, haemodynamic, and morphological features are described in 2 patients with disproportionate ventricular septal thickening, left ventricular outflow obstruction with systolic anterior motion of the anterior mitral leaflet, and either acquired or congenital heart disease. The disproportionate septal thickening in these patients appeared to be secondary to their underlying cardiac disease rather than a manifestation of genetically transmitted hypertrophic cardiomyopathy. One patient with combined aortic and mitral stenosis had severe systolic anterior motion of the anterior mitral leaflet and a residual large systolic pressure gradient between left ventricle and systemic artery after aortic valve replacement. In this patient the systolic anterior motion was evident in the presence of mitral valve stenosis. The other patient with mild aortic stenosis and a previously repaired coarctation of the aorta also had mild systolic anterior motion and a small subaortic systolic pressure gradient. Hence, these 2 patients demonstrate that disproportionate septal thickening secondary to acquired or congenital heart disease may be associated with left ventricular outflow obstruction and systolic anterior motion of the anterior mitral leaflet."} {"id": "PMID:154916", "title": "Pulsus alternans induced by glyceryl trinitrate paste in a patient with alcoholic cardiomyopathy.", "content": "Application of a small dose of glyceryl trinitrate paste (0.25 in) resulted in severe left ventricular dysfunction with the appearance of pulsus alternans in a patient with alcoholic cardiomyopathy. The echocardiogram showed a reduction in the amplitude and velocity of motion of the left ventricular posterior wall on alternate beats. Leg elevation promptly reversed the pulsus alternans, and the echocardiographic abnormality. Glyceryl trinitrate paste should be used with caution and under close supervision in patients with liver dysfunction.", "contents": "Pulsus alternans induced by glyceryl trinitrate paste in a patient with alcoholic cardiomyopathy. Application of a small dose of glyceryl trinitrate paste (0.25 in) resulted in severe left ventricular dysfunction with the appearance of pulsus alternans in a patient with alcoholic cardiomyopathy. The echocardiogram showed a reduction in the amplitude and velocity of motion of the left ventricular posterior wall on alternate beats. Leg elevation promptly reversed the pulsus alternans, and the echocardiographic abnormality. Glyceryl trinitrate paste should be used with caution and under close supervision in patients with liver dysfunction."} {"id": "PMID:154917", "title": "Accuracy of gas flowmeters determined by the bubble meter method.", "content": "THe accuracy of 15 oxygen and nitrous oxide flowmeter units in daily use was investigated using the bubble meter method. At preset oxygen flow rates of less than 1 litre min-1 unacceptable errors were found. At flow settings greater than 1 litre min-1 the deviations varied within closer limits, but the actural flows were inaccurate irrespective of the presettings and of the gas delivered, and independent of the indicator being adjusted to be opposite or between the graduation marks on the flowmeter.", "contents": "Accuracy of gas flowmeters determined by the bubble meter method. THe accuracy of 15 oxygen and nitrous oxide flowmeter units in daily use was investigated using the bubble meter method. At preset oxygen flow rates of less than 1 litre min-1 unacceptable errors were found. At flow settings greater than 1 litre min-1 the deviations varied within closer limits, but the actural flows were inaccurate irrespective of the presettings and of the gas delivered, and independent of the indicator being adjusted to be opposite or between the graduation marks on the flowmeter."} {"id": "PMID:154920", "title": "Drugs causing fixed eruptions.", "content": "Forty patients having fixed drug eruptions were subjected to provocation tests. Twelve patients failed to complete the provocation tests while in the remaining, the causative drugs were shown to be tetracyclines (6), analgin (metamizole) (6), oxyphenbutazone (5), phenobarbitone (4), sulphadiazine (3), sulphaphenazole (2), penicillin (1), suphadimethoxone (1), Saridon (1), sulphadimidine (1) and sulphamethoxypryridazine (1). There was evidence of cross-sensitivity between tetracycline and demethylchlortetracycline and also between exyphenbutazone and phenylbutazone, but not between different sulphonamides, In 2 cases, the minimum dose of the drug capable of reactivating the lesions was 100 mg of sulphadiazine and 50 mg of Saridon respectively.", "contents": "Drugs causing fixed eruptions. Forty patients having fixed drug eruptions were subjected to provocation tests. Twelve patients failed to complete the provocation tests while in the remaining, the causative drugs were shown to be tetracyclines (6), analgin (metamizole) (6), oxyphenbutazone (5), phenobarbitone (4), sulphadiazine (3), sulphaphenazole (2), penicillin (1), suphadimethoxone (1), Saridon (1), sulphadimidine (1) and sulphamethoxypryridazine (1). There was evidence of cross-sensitivity between tetracycline and demethylchlortetracycline and also between exyphenbutazone and phenylbutazone, but not between different sulphonamides, In 2 cases, the minimum dose of the drug capable of reactivating the lesions was 100 mg of sulphadiazine and 50 mg of Saridon respectively."} {"id": "PMID:154921", "title": "Comparative evaluation of skin atrophy in man induced by topical corticoids.", "content": "In this in-patient study, mild skin atrophy was observed clinically in 6 out of a total of 22 patients after fluocinolone acetonide and in one patient after flumethasone pivalate ointment applications (P less than 0,05). Investigations were discontinued prematurely on days 14 and 17 in 2 patients because they developed early atrophy due to fluocinolone acetonide applications. Histological findings indicating either moderate or marked skin atrophy were evident in 15 patients after flucinolone acetonide as against one patient after flumethasone pivalate ointment applications (P less than 0.001). In comparison with the controls the mean decrease in epidermal thickness was more marked after fluocinolone acetonide applications, namely 30.5% vs 21.3% after flumethasone pivalate applications. The ultrastructural tissue changes were less marked at the sites to which flumethasone pivalate was applied. In comparison with controls, the percentages of mean decrease in diameters of collagen fibrils measured in six volunteer patients ranged from 5.1% to 27.6% after fluocinolone acetonide and from 0% to 12.3% following flumethasone pivalate ointment applications, This difference was statistically significant (range P less than 0,01 to less than 0.001). This experimental study has demonstrated that flumethasone pivalate displays only a mild atrophogenic effect and it is clinically and histologically significantly less atrophogenic than fluocinolone acetonide. Flumethasone pivalate can therefore be reckoned as a suitable topical corticosteroid especially for the long-term treatment of corticoid-responsive dermatoses.", "contents": "Comparative evaluation of skin atrophy in man induced by topical corticoids. In this in-patient study, mild skin atrophy was observed clinically in 6 out of a total of 22 patients after fluocinolone acetonide and in one patient after flumethasone pivalate ointment applications (P less than 0,05). Investigations were discontinued prematurely on days 14 and 17 in 2 patients because they developed early atrophy due to fluocinolone acetonide applications. Histological findings indicating either moderate or marked skin atrophy were evident in 15 patients after flucinolone acetonide as against one patient after flumethasone pivalate ointment applications (P less than 0.001). In comparison with the controls the mean decrease in epidermal thickness was more marked after fluocinolone acetonide applications, namely 30.5% vs 21.3% after flumethasone pivalate applications. The ultrastructural tissue changes were less marked at the sites to which flumethasone pivalate was applied. In comparison with controls, the percentages of mean decrease in diameters of collagen fibrils measured in six volunteer patients ranged from 5.1% to 27.6% after fluocinolone acetonide and from 0% to 12.3% following flumethasone pivalate ointment applications, This difference was statistically significant (range P less than 0,01 to less than 0.001). This experimental study has demonstrated that flumethasone pivalate displays only a mild atrophogenic effect and it is clinically and histologically significantly less atrophogenic than fluocinolone acetonide. Flumethasone pivalate can therefore be reckoned as a suitable topical corticosteroid especially for the long-term treatment of corticoid-responsive dermatoses."} {"id": "PMID:154922", "title": "Surgery for trachoma in Burma.", "content": "The problem of trachoma in Burma is presented. For its major sight-threatening complication of trichiasis a surgical procedure is described which is simple, effective, economical, and without any cosmetic blemish. With this procedure 1861 cases of different grades of trichiasis were operated upon at the Eye, ENT Hospital, Rangoon, with 528 cases followed up at 1 year. The results are entirely satisfactory when the operations are performed for first and second degree trichiasis, and for trichiasis of our third degree grading the success rate is 95%.", "contents": "Surgery for trachoma in Burma. The problem of trachoma in Burma is presented. For its major sight-threatening complication of trichiasis a surgical procedure is described which is simple, effective, economical, and without any cosmetic blemish. With this procedure 1861 cases of different grades of trichiasis were operated upon at the Eye, ENT Hospital, Rangoon, with 528 cases followed up at 1 year. The results are entirely satisfactory when the operations are performed for first and second degree trichiasis, and for trichiasis of our third degree grading the success rate is 95%."} {"id": "PMID:154923", "title": "Primary soluble plasmic degradation product of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E complex.", "content": "The formation of the (DD)E complex and fragments DD and E upon proteolysis of human cross-linked fibrin was studied by timed digestions using varying amounts of plasmin. The (DD)E complex was the primary soluble degradation product released form cross-linked fibrin. This complex contained fragments DD and E1. Upon further digestion (DD)E1 complex was cleaved to (DD)E2 complex whereby only the fragment E moiety was affected. However, when fragment E2 was digested to fragment E3, dissociation of the complex occurred. Thus, fragments DD and E3 are the terminal plasmic digestion products of cross-linked fibrin. This pattern was consistent regardless of the plasmin to fibrin ratio; however, the rate of production of the terminal degradation products was directly dependent upon enzyme concentration. Digestion conditions were modified so that either the (DD)E complex or fragment DD was the predominant degradation product, allowing for the purification of these species by one-step gel filtration. The molar ratio of fragment DD to fragment E in the (DD)E complex was investigated by dissociation of the complex and by reassociation of the purified components. The (DD)E complex contains one molecule of fragment DD and one molecule of fragment E.", "contents": "Primary soluble plasmic degradation product of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E complex. The formation of the (DD)E complex and fragments DD and E upon proteolysis of human cross-linked fibrin was studied by timed digestions using varying amounts of plasmin. The (DD)E complex was the primary soluble degradation product released form cross-linked fibrin. This complex contained fragments DD and E1. Upon further digestion (DD)E1 complex was cleaved to (DD)E2 complex whereby only the fragment E moiety was affected. However, when fragment E2 was digested to fragment E3, dissociation of the complex occurred. Thus, fragments DD and E3 are the terminal plasmic digestion products of cross-linked fibrin. This pattern was consistent regardless of the plasmin to fibrin ratio; however, the rate of production of the terminal degradation products was directly dependent upon enzyme concentration. Digestion conditions were modified so that either the (DD)E complex or fragment DD was the predominant degradation product, allowing for the purification of these species by one-step gel filtration. The molar ratio of fragment DD to fragment E in the (DD)E complex was investigated by dissociation of the complex and by reassociation of the purified components. The (DD)E complex contains one molecule of fragment DD and one molecule of fragment E."} {"id": "PMID:154924", "title": "Effect of organic solvents on the beef heart mitochondrial adenosine triphosphatase.", "content": "The effect of organic solvents on the beef heart mitochondrial ATP-base-catalyzed ATP and ITP hydrolysis was examined. It was observed that numerous organic solvents stimulated ATP hydrolysis while ITP hydrolysis was inhibited. Methanol at 20% (v/v) was found to stimulate ATP hydrolysis by over 300%, while at the same methanol concentration ITP hydrolysis was inhibited approximately 50%. In the presence of 20% methanol, ATP hydrolysis exhibited linear plots of 1/[ATP] vs. 1/v, while in the absence of methanol negative cooperativity was observed. These data can be interpreted to imply that the catalytic and regulatory sites of the mitochondrial ATPase are being dissociated 20% methanol. The effect of methanol on the hydrolysis of ATP and ITP was examined as a function of pH. It was found that, at high pH in totally aqueous solutions, the hydrolysis of ATP and ITP was inhibited, while the presence of 20% methanol either caused the hydrolytic rate to peak and remain constant above pH 8 (with ATP as substrate) or caused the rate of hydrolysis to continue to increase above pH 8 (when ITP was the substrate). These data are interpreted to indicate that an acidic group in the active site may be ionizing, limiting the ATPase-catalyzed hydrolytic rate, and, with 20% methanol, this ionization was inhibited.", "contents": "Effect of organic solvents on the beef heart mitochondrial adenosine triphosphatase. The effect of organic solvents on the beef heart mitochondrial ATP-base-catalyzed ATP and ITP hydrolysis was examined. It was observed that numerous organic solvents stimulated ATP hydrolysis while ITP hydrolysis was inhibited. Methanol at 20% (v/v) was found to stimulate ATP hydrolysis by over 300%, while at the same methanol concentration ITP hydrolysis was inhibited approximately 50%. In the presence of 20% methanol, ATP hydrolysis exhibited linear plots of 1/[ATP] vs. 1/v, while in the absence of methanol negative cooperativity was observed. These data can be interpreted to imply that the catalytic and regulatory sites of the mitochondrial ATPase are being dissociated 20% methanol. The effect of methanol on the hydrolysis of ATP and ITP was examined as a function of pH. It was found that, at high pH in totally aqueous solutions, the hydrolysis of ATP and ITP was inhibited, while the presence of 20% methanol either caused the hydrolytic rate to peak and remain constant above pH 8 (with ATP as substrate) or caused the rate of hydrolysis to continue to increase above pH 8 (when ITP was the substrate). These data are interpreted to indicate that an acidic group in the active site may be ionizing, limiting the ATPase-catalyzed hydrolytic rate, and, with 20% methanol, this ionization was inhibited."} {"id": "PMID:154926", "title": "A possible mechanism for the increased oxidation of choline after chronic ethanol ingestion.", "content": "An attempt has been made to determine the location of the site at which the metabolism of ethanol interacts with that of choline to produce an increase in the oxidation of choline. The first enzyme in the oxidation pathway for choline, choline dehydrogenase, was assayed using a newly developed spectrophotometric assay and freshly isolated intact rat liver mitochondria. No changes were observed in either 'apparent' V or the 'apparent' Km values of choline dehydrogenase for choline after ethanol ingestion. However, when the choline oxidase system was assayed, a 28% decrease in 'apparent' Km for choline and a 53% increase in 'apparent' V was observed. The effects of ATP on choline oxidase were studied further, and a 29.4% decrease was observed in mitochondrial ATP levels from freshly isolated mitochondria from the ethanol-treated rats. In vitro aging of mitochondria further decreased the level of ATP, and the rate of decrease was considerably faster during the first hour in the mitochondria from the ethanol-treated animals. The decreases in ATP from both control and experimental mitochondria were accompanied by increases in choline oxidase activity. The initial decrease in ATP was correlated with an increase in mitochondrial ATPase activity which may be related to an increase in mitochondria Mg2+. Because chronic ethanol ingestion has resulted in decreased oxidation rates of succinate and beta-hydroxybutyrate while at the same time increasing the oxidation rates of choline, the studies reported here suggest that the effect of chronic ethanol ingestion is primarily on a step that is unique to choline and which probably exists prior to the electron transport chain.", "contents": "A possible mechanism for the increased oxidation of choline after chronic ethanol ingestion. An attempt has been made to determine the location of the site at which the metabolism of ethanol interacts with that of choline to produce an increase in the oxidation of choline. The first enzyme in the oxidation pathway for choline, choline dehydrogenase, was assayed using a newly developed spectrophotometric assay and freshly isolated intact rat liver mitochondria. No changes were observed in either 'apparent' V or the 'apparent' Km values of choline dehydrogenase for choline after ethanol ingestion. However, when the choline oxidase system was assayed, a 28% decrease in 'apparent' Km for choline and a 53% increase in 'apparent' V was observed. The effects of ATP on choline oxidase were studied further, and a 29.4% decrease was observed in mitochondrial ATP levels from freshly isolated mitochondria from the ethanol-treated rats. In vitro aging of mitochondria further decreased the level of ATP, and the rate of decrease was considerably faster during the first hour in the mitochondria from the ethanol-treated animals. The decreases in ATP from both control and experimental mitochondria were accompanied by increases in choline oxidase activity. The initial decrease in ATP was correlated with an increase in mitochondrial ATPase activity which may be related to an increase in mitochondria Mg2+. Because chronic ethanol ingestion has resulted in decreased oxidation rates of succinate and beta-hydroxybutyrate while at the same time increasing the oxidation rates of choline, the studies reported here suggest that the effect of chronic ethanol ingestion is primarily on a step that is unique to choline and which probably exists prior to the electron transport chain."} {"id": "PMID:154927", "title": "F1-ATPase from different submitochondrial particles.", "content": "1. F1-ATPase has been extracted by the diphosphatidylglycerol procedure from mitochondrial ATPase complexes that differ in ATPase activity, cold stability, ATPase inhibitor and magnesium content. 2. The ATPase activity of the isolated enzymes was dependent upon the activity of the original particles. In this respect, F1-ATPase extracted from submitochondrial particles prepared in ammonia (pH 9.2) and filtered through Sephadex G-50 was comparable to the enzyme purified by conventional procedures (Horstman, L.L. and Racker, E. (1970) J. Biol. Chem. 245, 1336--1344), whereas F1-ATPase extracted from submitochondrial particles prepared in the presence of magnesium and ATP at neutral pH was similar to factor A (Andreoli, T.E., Lam, K.W. and Sanadi, D.R. (1965) J. Biol. Chem. 240, 2644--2653). 3. No systematic relationship has been found in these F1-ATPase preparations between their ATPase inhibitor content and ATPase activity. Rather, a relationship has been observed between this activity and the efficiency of the ATPase inhibitor-F1-ATPase association within the membrane. 4. It is concluded that the ATPase activity of isolated F1-ATPase reflects the properties of original ATPase complex provided a rapid and not denaturing procedure of isolation is employed.", "contents": "F1-ATPase from different submitochondrial particles. 1. F1-ATPase has been extracted by the diphosphatidylglycerol procedure from mitochondrial ATPase complexes that differ in ATPase activity, cold stability, ATPase inhibitor and magnesium content. 2. The ATPase activity of the isolated enzymes was dependent upon the activity of the original particles. In this respect, F1-ATPase extracted from submitochondrial particles prepared in ammonia (pH 9.2) and filtered through Sephadex G-50 was comparable to the enzyme purified by conventional procedures (Horstman, L.L. and Racker, E. (1970) J. Biol. Chem. 245, 1336--1344), whereas F1-ATPase extracted from submitochondrial particles prepared in the presence of magnesium and ATP at neutral pH was similar to factor A (Andreoli, T.E., Lam, K.W. and Sanadi, D.R. (1965) J. Biol. Chem. 240, 2644--2653). 3. No systematic relationship has been found in these F1-ATPase preparations between their ATPase inhibitor content and ATPase activity. Rather, a relationship has been observed between this activity and the efficiency of the ATPase inhibitor-F1-ATPase association within the membrane. 4. It is concluded that the ATPase activity of isolated F1-ATPase reflects the properties of original ATPase complex provided a rapid and not denaturing procedure of isolation is employed."} {"id": "PMID:154928", "title": "Tentoxin-induced binding of adenine nucleotides to soluble spinach chloroplast coupling factor 1.", "content": "The effect of tentoxin on the binding of adenine nucleotides to soluble chloroplast coupling factor (CF1) has been studied and the following results have been obtained: 1. Tentoxin (400 micron) increases the maximum attainable tight binding of ADP to CF1. In the absence of tentoxin, the maximal binding observed by the method employed is about 0.3 nmol ADP/mg protein, whereas in the presence of tentoxin this ranges from 1.5 to 2.0 nmol ADP/mg protein. 2. Tentoxin-induced binding of ADP to CF1 is severely inhibited by divalent cations (50% inhibition at about 2 mM) but only weakly inhibited by monovalent cations (less than 50% inhibition at 100 mM). 3. The binding of ADP to CF1 induced by tentoxin is inhibited by ATP and adenylyl imidodiphosphate but is not inhibited by other nucleotides including AMP, GDP, CDP, IDP, or beta, gamma-methylene ATP. 4. The ADP-CF1 complex induced by tentoxin is quite stable. 75% remains bound to CF1 even after passage of the complex through a gel filtration column. An additional 25% can be removed by incubation in the presence of ADP, and all of the bound ADP can be removed only after incubation in the presence of both tentoxin and ADP. The latter result is interpreted as a tentoxin-induced exchange of bound ADP for medium ADP.", "contents": "Tentoxin-induced binding of adenine nucleotides to soluble spinach chloroplast coupling factor 1. The effect of tentoxin on the binding of adenine nucleotides to soluble chloroplast coupling factor (CF1) has been studied and the following results have been obtained: 1. Tentoxin (400 micron) increases the maximum attainable tight binding of ADP to CF1. In the absence of tentoxin, the maximal binding observed by the method employed is about 0.3 nmol ADP/mg protein, whereas in the presence of tentoxin this ranges from 1.5 to 2.0 nmol ADP/mg protein. 2. Tentoxin-induced binding of ADP to CF1 is severely inhibited by divalent cations (50% inhibition at about 2 mM) but only weakly inhibited by monovalent cations (less than 50% inhibition at 100 mM). 3. The binding of ADP to CF1 induced by tentoxin is inhibited by ATP and adenylyl imidodiphosphate but is not inhibited by other nucleotides including AMP, GDP, CDP, IDP, or beta, gamma-methylene ATP. 4. The ADP-CF1 complex induced by tentoxin is quite stable. 75% remains bound to CF1 even after passage of the complex through a gel filtration column. An additional 25% can be removed by incubation in the presence of ADP, and all of the bound ADP can be removed only after incubation in the presence of both tentoxin and ADP. The latter result is interpreted as a tentoxin-induced exchange of bound ADP for medium ADP."} {"id": "PMID:154929", "title": "The carbohydrate prosthetic groups of rat fibrinogen plasmic fragment E.", "content": "Rat fibrinogen plasmic fragment E was found to contain one oligosaccharide chain per gamma-chain attached by a glycosylamine linkage. The oligosaccharide was composed of 1 sialic acid, 1 galactose, 2 mannose and 2 glucosamine residues. The probable sequence from the nonreducing end was sialic acid leads to galactose beta leads to mannose alpha leads to mannose alpha leads to glucosamine leads to glucosamine. No difference in the rate of clearance from the rat circulation could be detected between native and desialated fragment E. A non-denaturing method for the purification of fragment E is described.", "contents": "The carbohydrate prosthetic groups of rat fibrinogen plasmic fragment E. Rat fibrinogen plasmic fragment E was found to contain one oligosaccharide chain per gamma-chain attached by a glycosylamine linkage. The oligosaccharide was composed of 1 sialic acid, 1 galactose, 2 mannose and 2 glucosamine residues. The probable sequence from the nonreducing end was sialic acid leads to galactose beta leads to mannose alpha leads to mannose alpha leads to glucosamine leads to glucosamine. No difference in the rate of clearance from the rat circulation could be detected between native and desialated fragment E. A non-denaturing method for the purification of fragment E is described."} {"id": "PMID:154930", "title": "Nature of the phosphorylated 26 000 molecular weight protein extracted from dog thyroid with contractile proteins.", "content": "Dog thyroid contractile proteins are characterized by their ATPase activity at high KCl concentration. In the presence of Ca(2+), 80 nmol ATP are hydrolyzed per min per mg protein. This Ca(2+) -ATPase activity is inhibited by Mg(2+) but not influenced by sodium azide. The 26 000 molecular weight protein which is present in thyroid contractile protein preparations and the phosphorylation of which is stimulated by thyroid stimulating hormone (TSH) is suggested to be identical to the lysine-rich histones (H1). Indeed, radioactive thyroid H1 histones added to unlabelled thyroid slices copurify with the contractile proteins and migrate at the same level as the 26 000 molecular weight when submitted to electrophoresis in polyacrylamide sodium dodecyl sulfate gels of different acrylamide concentrations.", "contents": "Nature of the phosphorylated 26 000 molecular weight protein extracted from dog thyroid with contractile proteins. Dog thyroid contractile proteins are characterized by their ATPase activity at high KCl concentration. In the presence of Ca(2+), 80 nmol ATP are hydrolyzed per min per mg protein. This Ca(2+) -ATPase activity is inhibited by Mg(2+) but not influenced by sodium azide. The 26 000 molecular weight protein which is present in thyroid contractile protein preparations and the phosphorylation of which is stimulated by thyroid stimulating hormone (TSH) is suggested to be identical to the lysine-rich histones (H1). Indeed, radioactive thyroid H1 histones added to unlabelled thyroid slices copurify with the contractile proteins and migrate at the same level as the 26 000 molecular weight when submitted to electrophoresis in polyacrylamide sodium dodecyl sulfate gels of different acrylamide concentrations."} {"id": "PMID:154932", "title": "Pulmonary vascular reactivity in the spontaneously hypertensive rat.", "content": "We examined the pulmonary vascular reactivity of normotensive rats (NR) and spontaneously hypertensive rats (SHR) to acute and chronic pressor stimuli. In rats kept at low altitude (1,520 m), SHR had a slight degree of right ventricular hypertrophy, but there was no difference between SHR and NR in either right ventricular systolic pressure or pulmonary artery wall thickness. When compared to blood-perfused lungs from low altitude NR, lungs from low altitude SHR were normoresponsive to acute airway hypoxia, hyporesponsive to intra-arterial angiotensin II, and hyperresponsive to intra-arterial prostaglandin F2alpha. After exposing rats to simulated high altitude (4--6 weeks at 4,270 m) to induce hypoxic pulmonary hypertension, SHR had a higher right ventricular systolic pressure, a greater degree of right ventricular hypertrophy, and more pulmonary artery medial thickening than did NR. The results indicate that although the pulmonary vasculature of SHR does not become hypertensive spontaneously, it might have an increased tendency to develop hypertension when exposed to an appropriate stimulus, i.e., chronic airway hypoxia.", "contents": "Pulmonary vascular reactivity in the spontaneously hypertensive rat. We examined the pulmonary vascular reactivity of normotensive rats (NR) and spontaneously hypertensive rats (SHR) to acute and chronic pressor stimuli. In rats kept at low altitude (1,520 m), SHR had a slight degree of right ventricular hypertrophy, but there was no difference between SHR and NR in either right ventricular systolic pressure or pulmonary artery wall thickness. When compared to blood-perfused lungs from low altitude NR, lungs from low altitude SHR were normoresponsive to acute airway hypoxia, hyporesponsive to intra-arterial angiotensin II, and hyperresponsive to intra-arterial prostaglandin F2alpha. After exposing rats to simulated high altitude (4--6 weeks at 4,270 m) to induce hypoxic pulmonary hypertension, SHR had a higher right ventricular systolic pressure, a greater degree of right ventricular hypertrophy, and more pulmonary artery medial thickening than did NR. The results indicate that although the pulmonary vasculature of SHR does not become hypertensive spontaneously, it might have an increased tendency to develop hypertension when exposed to an appropriate stimulus, i.e., chronic airway hypoxia."} {"id": "PMID:154935", "title": "Whole gut irrigation: a survey of patient opinion.", "content": "Patients' assessment of whole gut irrigation via a nasogastric tube has been obtained by a questionnaire answered by 79 of 99 patients who received this method of bowel preparation before operation on the large bowel or colonoscopy. Abdominal pain during the irrigation was experienced by 13 patients (17 per cent) and nausea and vomiting occurred in 24 (30 per cent). Intubation with a nasogastric tube and the discomfort of prolonged sitting on a commode were considered the most disagreeable aspects of the procedure. Fifty-six patients (71 per cent) would have agreed to the irrigation being repeated if necessary and many patients preferred whole gut irrigation to previous 'orthodox' bowel preparations that they had experienced.", "contents": "Whole gut irrigation: a survey of patient opinion. Patients' assessment of whole gut irrigation via a nasogastric tube has been obtained by a questionnaire answered by 79 of 99 patients who received this method of bowel preparation before operation on the large bowel or colonoscopy. Abdominal pain during the irrigation was experienced by 13 patients (17 per cent) and nausea and vomiting occurred in 24 (30 per cent). Intubation with a nasogastric tube and the discomfort of prolonged sitting on a commode were considered the most disagreeable aspects of the procedure. Fifty-six patients (71 per cent) would have agreed to the irrigation being repeated if necessary and many patients preferred whole gut irrigation to previous 'orthodox' bowel preparations that they had experienced."} {"id": "PMID:154937", "title": "Effects of para-chlorophenylalanine on amphetamine and haloperidol-induced changes in striatal dopamine turnover.", "content": "Para-chlorophenylalanine (PCPA) was administered to rats, and the animals were sacrificed 48 h later. Animals received various doses of S(+)-amphetamine (AMPH) 31 min before sacrifice or of haloperidol (HAL) 46 min before sacrifice and an intracerebral injection of [3H]tyrosine 15 min prior to sacrifice. PCPA pretreatment potentiated the increased accumulation of striatal [3H]dopamine (DA) induced by doses of AMPH to 1.5 mg/kg, and inhibited the decrease in striatal [3H]DA accumulation observed at higher doses (greater than 2.5 mg/kg) of AMPH. Further, the AMPH-induced increase in endogenous levels of striatal DA was inhibited by PCPA pretreatment. Similarly, PCPA pretreatment potentiated the HAL-induced increase in striatal [3H]DA accumulation. The data are discussed with respect to an inhibitory serotonergic influence on nigrostriatal DA function, and the relationship of nigrostriatal biochemical events to AMPH-induced behavioral changes.", "contents": "Effects of para-chlorophenylalanine on amphetamine and haloperidol-induced changes in striatal dopamine turnover. Para-chlorophenylalanine (PCPA) was administered to rats, and the animals were sacrificed 48 h later. Animals received various doses of S(+)-amphetamine (AMPH) 31 min before sacrifice or of haloperidol (HAL) 46 min before sacrifice and an intracerebral injection of [3H]tyrosine 15 min prior to sacrifice. PCPA pretreatment potentiated the increased accumulation of striatal [3H]dopamine (DA) induced by doses of AMPH to 1.5 mg/kg, and inhibited the decrease in striatal [3H]DA accumulation observed at higher doses (greater than 2.5 mg/kg) of AMPH. Further, the AMPH-induced increase in endogenous levels of striatal DA was inhibited by PCPA pretreatment. Similarly, PCPA pretreatment potentiated the HAL-induced increase in striatal [3H]DA accumulation. The data are discussed with respect to an inhibitory serotonergic influence on nigrostriatal DA function, and the relationship of nigrostriatal biochemical events to AMPH-induced behavioral changes."} {"id": "PMID:154938", "title": "Histophysiological observations on fast skeleto-fusimotor axons.", "content": "In three instances, repetitive stimulation of a single fast skeleto-fusimotor axon supplying cat tenuissimus muscle was observed to activate a secondary ending belonging to a precisely located spindle. Prolonged repetitive stimulation of these beta-axons elicited glycogen depletion in the intrafusal muscle fibres of the located spindles and in extrafusal fibres. The intrafusal depletion affected the longest of the chain fibres in two instances, and the bag1 and bag2 fibres in the third instance. In one experiment, the discharge from the primary ending of the located spindle was also recorded. The fast beta-axon (it supplied the longest chain fibre in the spindle) had a static action on the primary ending. The extrafusal muscle fibres of the 3 fast beta-motor units belonged to the fast oxidative-glycolytic type.", "contents": "Histophysiological observations on fast skeleto-fusimotor axons. In three instances, repetitive stimulation of a single fast skeleto-fusimotor axon supplying cat tenuissimus muscle was observed to activate a secondary ending belonging to a precisely located spindle. Prolonged repetitive stimulation of these beta-axons elicited glycogen depletion in the intrafusal muscle fibres of the located spindles and in extrafusal fibres. The intrafusal depletion affected the longest of the chain fibres in two instances, and the bag1 and bag2 fibres in the third instance. In one experiment, the discharge from the primary ending of the located spindle was also recorded. The fast beta-axon (it supplied the longest chain fibre in the spindle) had a static action on the primary ending. The extrafusal muscle fibres of the 3 fast beta-motor units belonged to the fast oxidative-glycolytic type."} {"id": "PMID:154942", "title": "[Mechanism of action of antibiotics:some examples].", "content": "Antibiotics are very commonly used substances to eradicate bacterial infections by bacteriostatic or even bactericid effect. They act at a very specific stage (target), although other less important or secondary interactions can occur. We studied the interaction of three antibiotic families (beta-lactamins, aminosides, rifampicin) with bacterial cell. Penicillin disturbs the cell wall synthesis and more accurately the glycopeptide (or murein) formation, a substance giving rigidity or shape to bacteria. It acts in the late phase of murein-biosynthesis, when N-acetyl glucosamin -- N-acetyl muramic acid L ala -D glu M-DAP (L lys) -D ala -D ala are linked together by the peptide part, under the effect of several enzymes, particularly transpeptidase and DD-carboxy-peptidase. It would appear that beta-lactame-thiazolidine rings have a steric analogy with dipeptide D-alanyl D-alanine. The result would be that the enzyme would act on the antibiotic instead of peptide: the consequence would be inhibition of the peptidic link, giving an abnormal murein, and an incomplete cell wall i.e. fragile bacteria. Aminosides, particularly Streptomycin, link themselves to 30 S subunit of bacterial ribosome. In this case, it seems that it is a 3''OH function which reacts with lysine (from S 12 protein part of 30 S subunit). The consequence is an alteration in the RNA messager lecture, and a false traduction and consequently protein biosynthesis stops with a decrease of polyribosomes and of the formation of inert 70 S ribosome. Rifamycins, and particularly Rifampicin act by inhibition of RNA messager synthesis. One molecule of antibiotic links itself to one molecule of RNA messager : hydroxyl and cetone function in C1 Cs C21 C23 and \"ansa\" bridge link to beta subunit of RNA polymerase. This linkage gives a conformational change to the RNA polymerase-DNA complex, inhibiting the catalytic action of this enzyme, and consequently stopping RNA messager and protein synthesis. The study of the action mechanism of these antibiotics enables us to show the action specificity of these products in the bacteria. This specificity is more accurate when the target is not to be found in the eucaryotic cells : in this case the antibiotic may be considered as entirely atoxic. If the study of the action mechanism of antibiotics gives a better understanding of the use of these drugs, their action at a definite stage in bacterial metabolism is a valuable tool for scientists in their approach to cell functioning.", "contents": "[Mechanism of action of antibiotics:some examples]. Antibiotics are very commonly used substances to eradicate bacterial infections by bacteriostatic or even bactericid effect. They act at a very specific stage (target), although other less important or secondary interactions can occur. We studied the interaction of three antibiotic families (beta-lactamins, aminosides, rifampicin) with bacterial cell. Penicillin disturbs the cell wall synthesis and more accurately the glycopeptide (or murein) formation, a substance giving rigidity or shape to bacteria. It acts in the late phase of murein-biosynthesis, when N-acetyl glucosamin -- N-acetyl muramic acid L ala -D glu M-DAP (L lys) -D ala -D ala are linked together by the peptide part, under the effect of several enzymes, particularly transpeptidase and DD-carboxy-peptidase. It would appear that beta-lactame-thiazolidine rings have a steric analogy with dipeptide D-alanyl D-alanine. The result would be that the enzyme would act on the antibiotic instead of peptide: the consequence would be inhibition of the peptidic link, giving an abnormal murein, and an incomplete cell wall i.e. fragile bacteria. Aminosides, particularly Streptomycin, link themselves to 30 S subunit of bacterial ribosome. In this case, it seems that it is a 3''OH function which reacts with lysine (from S 12 protein part of 30 S subunit). The consequence is an alteration in the RNA messager lecture, and a false traduction and consequently protein biosynthesis stops with a decrease of polyribosomes and of the formation of inert 70 S ribosome. Rifamycins, and particularly Rifampicin act by inhibition of RNA messager synthesis. One molecule of antibiotic links itself to one molecule of RNA messager : hydroxyl and cetone function in C1 Cs C21 C23 and \"ansa\" bridge link to beta subunit of RNA polymerase. This linkage gives a conformational change to the RNA polymerase-DNA complex, inhibiting the catalytic action of this enzyme, and consequently stopping RNA messager and protein synthesis. The study of the action mechanism of these antibiotics enables us to show the action specificity of these products in the bacteria. This specificity is more accurate when the target is not to be found in the eucaryotic cells : in this case the antibiotic may be considered as entirely atoxic. If the study of the action mechanism of antibiotics gives a better understanding of the use of these drugs, their action at a definite stage in bacterial metabolism is a valuable tool for scientists in their approach to cell functioning."} {"id": "PMID:154943", "title": "[Histochemistry of neurosecretory cells in the cerebral ganglion of the adult or juvenile sweet water crab, Potamon magnum magnum (Pretzman)].", "content": "The histochemistry of the neurosecretory material of the PF-positive neurosecretory cells of the cerebral ganglion of the adult and juvenile crab, Potamon magnum magnum (Pretzman) has been investigated. The PF-positive neurosecretory material is proteinaceous and contains considerable amounts of cystine; it is associated with significant amount of cytoplasmic RNA, lipids and phospholipids and with moderate amounts of carbohydrates, though no glycogen could be detected. The significance of these results is discussed.", "contents": "[Histochemistry of neurosecretory cells in the cerebral ganglion of the adult or juvenile sweet water crab, Potamon magnum magnum (Pretzman)]. The histochemistry of the neurosecretory material of the PF-positive neurosecretory cells of the cerebral ganglion of the adult and juvenile crab, Potamon magnum magnum (Pretzman) has been investigated. The PF-positive neurosecretory material is proteinaceous and contains considerable amounts of cystine; it is associated with significant amount of cytoplasmic RNA, lipids and phospholipids and with moderate amounts of carbohydrates, though no glycogen could be detected. The significance of these results is discussed."} {"id": "PMID:154944", "title": "[Evaluation of food intake and adrenergic response in rats during the tail pinch test].", "content": "The urinary catecholamines output and the food intake were investigated in two groups of rats: a control group and a group where Tail Pinches (T.P.) were performed. Our results have shown, as these of antelman and al., that the Tail Pinch induced a high concentrate milk consumption, in spite of an increase of adrenergic activity which is known to have an inhibitory effect on caloric intake. We suggest that the role of various stress on food intake dependes on the balance of these two antagonist effects.", "contents": "[Evaluation of food intake and adrenergic response in rats during the tail pinch test]. The urinary catecholamines output and the food intake were investigated in two groups of rats: a control group and a group where Tail Pinches (T.P.) were performed. Our results have shown, as these of antelman and al., that the Tail Pinch induced a high concentrate milk consumption, in spite of an increase of adrenergic activity which is known to have an inhibitory effect on caloric intake. We suggest that the role of various stress on food intake dependes on the balance of these two antagonist effects."} {"id": "PMID:154945", "title": "[Hemodynamic, functional and biochemical effects of hypobaric hypoxia in rats treated with cytidine diphosphocholine].", "content": "Treatment with cytidine diphosphocholine (20 mg/kg i.p.) in rats induces, during acute hypoxia, a reduction of vegetative responses (no modification of cerebral blood flow), a protection of conditioned avoidance response and a stabilization of dopamine and noradrenaline cerebral levels.", "contents": "[Hemodynamic, functional and biochemical effects of hypobaric hypoxia in rats treated with cytidine diphosphocholine]. Treatment with cytidine diphosphocholine (20 mg/kg i.p.) in rats induces, during acute hypoxia, a reduction of vegetative responses (no modification of cerebral blood flow), a protection of conditioned avoidance response and a stabilization of dopamine and noradrenaline cerebral levels."} {"id": "PMID:154946", "title": "[Effect of citidoline on hemodynamics in the normobaric hypoxic dog].", "content": "In dogs submitted to a normobaric hypoxia, we found an elevation of the arterial blood pressure, of the heart rate, of the cardiac output and of the regional blood flows, the total peripheral resistance remaining unchanged. Treatment with citidoline abolishes these hemodynamic responses and the authors hypothetize that this effect is correlated with the agonist dopaminergic effect of the drug.", "contents": "[Effect of citidoline on hemodynamics in the normobaric hypoxic dog]. In dogs submitted to a normobaric hypoxia, we found an elevation of the arterial blood pressure, of the heart rate, of the cardiac output and of the regional blood flows, the total peripheral resistance remaining unchanged. Treatment with citidoline abolishes these hemodynamic responses and the authors hypothetize that this effect is correlated with the agonist dopaminergic effect of the drug."} {"id": "PMID:154947", "title": "[Effect of different estro-progesterone sequences on nidation of dormant blastocysts administered in diapause in ovariectomized rats].", "content": "The hormonal condition permitting delayed nidation in rats ovarectomized on day 4 or 5 of pregnancy was studied by administering progesterone and estradiol in differents sequences between days 9 and 14. The best result was obtained when progesterone was given 3 days before an estrogen-progesterone association. The same treatment induced delayed nidation in rats receiving Reserpine and ovariectomized day 5, but not when progesterone and estradiol were present day 4.", "contents": "[Effect of different estro-progesterone sequences on nidation of dormant blastocysts administered in diapause in ovariectomized rats]. The hormonal condition permitting delayed nidation in rats ovarectomized on day 4 or 5 of pregnancy was studied by administering progesterone and estradiol in differents sequences between days 9 and 14. The best result was obtained when progesterone was given 3 days before an estrogen-progesterone association. The same treatment induced delayed nidation in rats receiving Reserpine and ovariectomized day 5, but not when progesterone and estradiol were present day 4."} {"id": "PMID:154948", "title": "[Lipid-protein interactions in blood serum].", "content": "The lipoprotein-fatty acid complexes show an electrophoretic mobility greater than that lipoproteins alone, but that phenomenon does not appear when those complexes have previously incubates for two days at 37 degrees C: an hypothesis on the evolution in time of the patterns of interaction binding lipoproteins and fatty acids has been confirmed by studies in isoelectric focusing.", "contents": "[Lipid-protein interactions in blood serum]. The lipoprotein-fatty acid complexes show an electrophoretic mobility greater than that lipoproteins alone, but that phenomenon does not appear when those complexes have previously incubates for two days at 37 degrees C: an hypothesis on the evolution in time of the patterns of interaction binding lipoproteins and fatty acids has been confirmed by studies in isoelectric focusing."} {"id": "PMID:154949", "title": "[Evidence and properties of digestive proteases in young mugilidae during the first year of life].", "content": "Proteolytic activity was observed in extracts from the digestive tract of Mugil auratus and Mugil capito; its maximum occurs at about pH 2 and 9. Activity in the acid range is mainly found in stomach extracts and the enzyme may be considered as similar to pepsin and cathepsins. In the alkaline range, the main activity is recorded in the region of the pyloric caeca. Activities of the trypsin, chymotrypsin, A and B carboxypeptidases and elastase type are found. The effects of pH and temperature on some activities are studied: optimal pH are about 2.6 and 3,4 with pepsin-like activity, between 8,1 and 8,5 with trypsin-like activity and between 7,8 and 8,5 with chymotrypsin-like activity; incubation optimal temperature (pH 2,2) is found between 35 degrees and 40 degrees.", "contents": "[Evidence and properties of digestive proteases in young mugilidae during the first year of life]. Proteolytic activity was observed in extracts from the digestive tract of Mugil auratus and Mugil capito; its maximum occurs at about pH 2 and 9. Activity in the acid range is mainly found in stomach extracts and the enzyme may be considered as similar to pepsin and cathepsins. In the alkaline range, the main activity is recorded in the region of the pyloric caeca. Activities of the trypsin, chymotrypsin, A and B carboxypeptidases and elastase type are found. The effects of pH and temperature on some activities are studied: optimal pH are about 2.6 and 3,4 with pepsin-like activity, between 8,1 and 8,5 with trypsin-like activity and between 7,8 and 8,5 with chymotrypsin-like activity; incubation optimal temperature (pH 2,2) is found between 35 degrees and 40 degrees."} {"id": "PMID:154950", "title": "[Immunocytological studies of C cells with anti-calcitonin or antisomatostatin immunoserums in rats treated with vitamin D, thyroxine or benzyl-thiouracil].", "content": "In rats treated with vitamin D3, thyroxin or BTU alone or with associations of vitamin D3 + BTU or vitamin D + thyroxin, immunocytochemical studies with an anti-human calcitonin serum show a stimulating effect of vitamin D and of thyroxin and an inhibiting effect of BTU on the C cells of the thyro\u00efd. These results are in agreement with the existence of functional relations between follicular and C cells. A few calcitonin-containing cells are immunoreactive to an anti-somatostatin serum. All the C cells contain both calcitonin and somatostatin when they are grouped in a single big interfollicular cluster.", "contents": "[Immunocytological studies of C cells with anti-calcitonin or antisomatostatin immunoserums in rats treated with vitamin D, thyroxine or benzyl-thiouracil]. In rats treated with vitamin D3, thyroxin or BTU alone or with associations of vitamin D3 + BTU or vitamin D + thyroxin, immunocytochemical studies with an anti-human calcitonin serum show a stimulating effect of vitamin D and of thyroxin and an inhibiting effect of BTU on the C cells of the thyro\u00efd. These results are in agreement with the existence of functional relations between follicular and C cells. A few calcitonin-containing cells are immunoreactive to an anti-somatostatin serum. All the C cells contain both calcitonin and somatostatin when they are grouped in a single big interfollicular cluster."} {"id": "PMID:154951", "title": "[Effect of propyl-2-pentene-2-oic acid on GABA levels in different regions of mouse brain].", "content": "An elevation in cerebral GABA level (65%) is observed after administration of an anticonvulsant, sodium propyl 2-pentene-2 oate, a branched chain fatty acid, comformationally restricted GABA analogue, competitive inhibitor of GABA-T in regard to GABA. The concentration of GABA increases in some regions i.e. substantia nigra, frontal and temporal cortex, cerebellum and olfactory bulbs. The GABA level remains unchanged in caudate nucleus, hippocampus and occipital cortex. Results are discussed comparatively to the effect of sodium n-dipropylacetate.", "contents": "[Effect of propyl-2-pentene-2-oic acid on GABA levels in different regions of mouse brain]. An elevation in cerebral GABA level (65%) is observed after administration of an anticonvulsant, sodium propyl 2-pentene-2 oate, a branched chain fatty acid, comformationally restricted GABA analogue, competitive inhibitor of GABA-T in regard to GABA. The concentration of GABA increases in some regions i.e. substantia nigra, frontal and temporal cortex, cerebellum and olfactory bulbs. The GABA level remains unchanged in caudate nucleus, hippocampus and occipital cortex. Results are discussed comparatively to the effect of sodium n-dipropylacetate."} {"id": "PMID:154952", "title": "[Action of hemocoagulase on the cicatrization of the dura mater in rabbits. Preliminary results].", "content": "The present study compares the cicatrization of the dura by administration of I.M. hemocoagulase. This study was done on 6 rabbits and 6 control animals. The authors think that the cicatrization is a little slower but of better quality. The hemocoagulase seems to favorize the vasculo-exsudative process of cicatrization. The fibrinous deposits are more important too. Perhaps the occlusion of C.S. fluid fistulas could be favorized by means of the used product. Definitive conclusions are not possible for the moment but a work on a larger scale is projected.", "contents": "[Action of hemocoagulase on the cicatrization of the dura mater in rabbits. Preliminary results]. The present study compares the cicatrization of the dura by administration of I.M. hemocoagulase. This study was done on 6 rabbits and 6 control animals. The authors think that the cicatrization is a little slower but of better quality. The hemocoagulase seems to favorize the vasculo-exsudative process of cicatrization. The fibrinous deposits are more important too. Perhaps the occlusion of C.S. fluid fistulas could be favorized by means of the used product. Definitive conclusions are not possible for the moment but a work on a larger scale is projected."} {"id": "PMID:154953", "title": "[Effect of dichlorophenolindophenol on glucose dehydrogenase activity of Pseudomonas fluorescens (type R)].", "content": "The glucose dehydrogenase activity of Pseudomonas fluorescens cells grown in iron-depleted synthetic media is strongly decreased (about 80%) by dichlorophenolindophenol (DIP) 2 X 10(-3) M. In those cells, DIP seems not to play the part of an ultimate electron acceptor.", "contents": "[Effect of dichlorophenolindophenol on glucose dehydrogenase activity of Pseudomonas fluorescens (type R)]. The glucose dehydrogenase activity of Pseudomonas fluorescens cells grown in iron-depleted synthetic media is strongly decreased (about 80%) by dichlorophenolindophenol (DIP) 2 X 10(-3) M. In those cells, DIP seems not to play the part of an ultimate electron acceptor."} {"id": "PMID:154954", "title": "[Dwarf colony mutants of Escherichia coli: plasmids resistant to antibiotics].", "content": "Deficient dwarf colony (DDC) mutants of E. coli K 12, harboring or no resistance plasmids, were obtained in vitro. The R plasmids of parental strains and to DDC mutants were transfered by conjugation to normal colony, and to DDC mutants of E. coli K 12; the frequencies of transfer were similar for all strains studied.", "contents": "[Dwarf colony mutants of Escherichia coli: plasmids resistant to antibiotics]. Deficient dwarf colony (DDC) mutants of E. coli K 12, harboring or no resistance plasmids, were obtained in vitro. The R plasmids of parental strains and to DDC mutants were transfered by conjugation to normal colony, and to DDC mutants of E. coli K 12; the frequencies of transfer were similar for all strains studied."} {"id": "PMID:154955", "title": "[Cellular material in urinary sediment in retarded or precocious puberty].", "content": "The cellular material studied in the urinary sediment mainly obtained from exfolied alls the bladder trigone was submitted to hormonal stimulation. These cell changes constitute the basis of a cytologic method called the urocytogram. The urocytogram was followed up in six children with early puberty and ten young girls with backward puberty. These repeated examinations contribute to the diagnosis and help in the differential diagnosis. Whenever it is necessary to investigate a child' sex hormones the urocytogram, simple painless method is indicated.", "contents": "[Cellular material in urinary sediment in retarded or precocious puberty]. The cellular material studied in the urinary sediment mainly obtained from exfolied alls the bladder trigone was submitted to hormonal stimulation. These cell changes constitute the basis of a cytologic method called the urocytogram. The urocytogram was followed up in six children with early puberty and ten young girls with backward puberty. These repeated examinations contribute to the diagnosis and help in the differential diagnosis. Whenever it is necessary to investigate a child' sex hormones the urocytogram, simple painless method is indicated."} {"id": "PMID:154956", "title": "[Urate transport in erythrocytes: possible role of a transport membrane].", "content": "Urate transport seems dependant of ATP. So, we studied urate behaviour in relation with the isolated membrane: we observed a linkage between urate and a membrane protein of which molecular weight was estimated to twenty thousand. The exact role of this protein remains to be clarify.", "contents": "[Urate transport in erythrocytes: possible role of a transport membrane]. Urate transport seems dependant of ATP. So, we studied urate behaviour in relation with the isolated membrane: we observed a linkage between urate and a membrane protein of which molecular weight was estimated to twenty thousand. The exact role of this protein remains to be clarify."} {"id": "PMID:154957", "title": "[Ventrobulbular hypotensive action of muscimol].", "content": "Muscimol, a rigid analogue of GABA has been injected in the CNS of urethane anesthetized, normotensive cats. Injected either intracisternally (1 or 2 microgram/kg, 0.05 ml) or directly by microinjection in a restricted ventrolateral region of the brain stem (0.5 or 1 microgram/kg, 0.5 microliter), muscimol induced hypotension and bradycardia. These central cardiovascular effects of muscimol were antagonized by bicuculline, a \"specific\" GABA antagonist agent. These data emphasize the involvement of gabergic mechanisms in the central cardiovascular control, at least in the ventrolateral part of the medulla oblongata.", "contents": "[Ventrobulbular hypotensive action of muscimol]. Muscimol, a rigid analogue of GABA has been injected in the CNS of urethane anesthetized, normotensive cats. Injected either intracisternally (1 or 2 microgram/kg, 0.05 ml) or directly by microinjection in a restricted ventrolateral region of the brain stem (0.5 or 1 microgram/kg, 0.5 microliter), muscimol induced hypotension and bradycardia. These central cardiovascular effects of muscimol were antagonized by bicuculline, a \"specific\" GABA antagonist agent. These data emphasize the involvement of gabergic mechanisms in the central cardiovascular control, at least in the ventrolateral part of the medulla oblongata."} {"id": "PMID:154958", "title": "[Intestinal tolerance in mice after low dose rate 60CO irradiation. Implications for radiotherapy].", "content": "Influence of absorbed dose rate has been studied in BALB/c mice for early intestinal tolerance. After selective abdominal irradiation, LD50 at 5.5 days increases from 12.36 to 20.22 and 21.79 Gy when dose rate decreases from 0.61 to 0.054 and 0.026 Gy/mn. LD50 at 6.5 days increases from 12.05 to 19.22 and 21.58 Gy respectively. The LD50 ratios are then 1.6 and 1.8 for both endpoints. After total body irradiation. LD50 at 5.5 days increases from 9.92 to 15.20and 16.83 Gy when dose rate decreases from 0.56 to 0.049 and 0.024 Gy/mn. The corresponding LD50 ratios, i.e. 1.5 and 1.7, are then similar to the former ones. Increase of LD50 when decreasing dose rate is in agreement with that expected taking into account only repair of sublethal lesions, for the generally accepted cellular models.", "contents": "[Intestinal tolerance in mice after low dose rate 60CO irradiation. Implications for radiotherapy]. Influence of absorbed dose rate has been studied in BALB/c mice for early intestinal tolerance. After selective abdominal irradiation, LD50 at 5.5 days increases from 12.36 to 20.22 and 21.79 Gy when dose rate decreases from 0.61 to 0.054 and 0.026 Gy/mn. LD50 at 6.5 days increases from 12.05 to 19.22 and 21.58 Gy respectively. The LD50 ratios are then 1.6 and 1.8 for both endpoints. After total body irradiation. LD50 at 5.5 days increases from 9.92 to 15.20and 16.83 Gy when dose rate decreases from 0.56 to 0.049 and 0.024 Gy/mn. The corresponding LD50 ratios, i.e. 1.5 and 1.7, are then similar to the former ones. Increase of LD50 when decreasing dose rate is in agreement with that expected taking into account only repair of sublethal lesions, for the generally accepted cellular models."} {"id": "PMID:154959", "title": "[RBE/absorbed dose relationship of d(50)-Be neutrons determine for early intestinal tolerance in mice].", "content": "RBE/absorbed dose realtionship of d(50)-Be neutrons (ref.: 60Co) was determined using intestinal tolerance in mice (LD50) after single and fractionated irradiation. RBE is 1.8 for a single fraction (about 1000 rad 60Co dose); it increases when decreasing dose and reaches the plateau value of 2.8 for a 60Co dose of about 200 rad. This RBE value is used for the clinical applications with the cyclotron \"Cyclone\" at Louvain-la-Neuve.", "contents": "[RBE/absorbed dose relationship of d(50)-Be neutrons determine for early intestinal tolerance in mice]. RBE/absorbed dose realtionship of d(50)-Be neutrons (ref.: 60Co) was determined using intestinal tolerance in mice (LD50) after single and fractionated irradiation. RBE is 1.8 for a single fraction (about 1000 rad 60Co dose); it increases when decreasing dose and reaches the plateau value of 2.8 for a 60Co dose of about 200 rad. This RBE value is used for the clinical applications with the cyclotron \"Cyclone\" at Louvain-la-Neuve."} {"id": "PMID:154960", "title": "[Organ cultures of mammalian testes. I. Adult mouse testis].", "content": "Organ cultures of adult normal mice testes have shown that the tubular structure is best preserved at 31 degrees C. With the simple anhormonal conditions we have used, the germ cells actively involved in meiosis disappear in ten days, following a stereotyped pattern. During the same time, Sertoli cells become enlarged, with a marked cytoplasmic vacuolisation. After 2 weeks in vitro, the seminiferous tubules are completely filled up with Sertoli cells and no more spermatocytes are recognized.", "contents": "[Organ cultures of mammalian testes. I. Adult mouse testis]. Organ cultures of adult normal mice testes have shown that the tubular structure is best preserved at 31 degrees C. With the simple anhormonal conditions we have used, the germ cells actively involved in meiosis disappear in ten days, following a stereotyped pattern. During the same time, Sertoli cells become enlarged, with a marked cytoplasmic vacuolisation. After 2 weeks in vitro, the seminiferous tubules are completely filled up with Sertoli cells and no more spermatocytes are recognized."} {"id": "PMID:154961", "title": "[Centromere staining in ten species of ruminants by C and R banding techniques].", "content": "The centromeric regions of acrocentric or telocentric chromosomes of 10 species of the order Artiodactyla, suborder Ruminantia, have shown to be equally deeply stained either with the C-banding or the R-banding technique. These unusual staining properties could be linked with the presence of a particular type of chromatin. The importance of centromeric fusions linked with speciation in the Bovoidea is recalled.", "contents": "[Centromere staining in ten species of ruminants by C and R banding techniques]. The centromeric regions of acrocentric or telocentric chromosomes of 10 species of the order Artiodactyla, suborder Ruminantia, have shown to be equally deeply stained either with the C-banding or the R-banding technique. These unusual staining properties could be linked with the presence of a particular type of chromatin. The importance of centromeric fusions linked with speciation in the Bovoidea is recalled."} {"id": "PMID:154962", "title": "[Peritoneal resorption of ethidium bromide, free or linked to DNA in rodents].", "content": "Ethidium bromide, either free (EB) or bound to DNA (EB-DNA), is injected into the peritoneal cavity of adult rats or mice. EB is then detected by fluorescence microscopy in peritoneal cells and by spectrophotometry in the peritoneal fluid. EB-DNA persists for a longer period of time in the peritoneal cavity than free EB does.", "contents": "[Peritoneal resorption of ethidium bromide, free or linked to DNA in rodents]. Ethidium bromide, either free (EB) or bound to DNA (EB-DNA), is injected into the peritoneal cavity of adult rats or mice. EB is then detected by fluorescence microscopy in peritoneal cells and by spectrophotometry in the peritoneal fluid. EB-DNA persists for a longer period of time in the peritoneal cavity than free EB does."} {"id": "PMID:154963", "title": "[Different types of virus inhibitory factors in interferon produced by different organs].", "content": "Fragments of organs from mice inoculated with Newcastle disease virus were incubated at 30 degrees C. Lungs and liver produced thermolabile virus-inhibiting factor (IF) or interferon at earlier stages. The spleen, lymph nodes and thymus produced thermolabile IF at earlier stages and thermostable IF at later stages.", "contents": "[Different types of virus inhibitory factors in interferon produced by different organs]. Fragments of organs from mice inoculated with Newcastle disease virus were incubated at 30 degrees C. Lungs and liver produced thermolabile virus-inhibiting factor (IF) or interferon at earlier stages. The spleen, lymph nodes and thymus produced thermolabile IF at earlier stages and thermostable IF at later stages."} {"id": "PMID:154964", "title": "[Hyper- and hypo-reactivity in mice with regard to the induction of virus inhibitory factor or interferon].", "content": "1. IF induction in mice with Newcastle disease virus produced hyperreactivity on subsequent induction with certain doses of poly I:C. 2. Laparotomy or intraperitoneal injection with air caused temporary hyporeactivity of spleen and lungs on IF induction with endotoxin. Laparotomy in splenectomised mice did not affect IF formation in lungs.", "contents": "[Hyper- and hypo-reactivity in mice with regard to the induction of virus inhibitory factor or interferon]. 1. IF induction in mice with Newcastle disease virus produced hyperreactivity on subsequent induction with certain doses of poly I:C. 2. Laparotomy or intraperitoneal injection with air caused temporary hyporeactivity of spleen and lungs on IF induction with endotoxin. Laparotomy in splenectomised mice did not affect IF formation in lungs."} {"id": "PMID:154965", "title": "Subcellular effects of some anesthetic agents on rat myocardium.", "content": "The effects of ether, chloroform, and halothane on calcium accumulation and ATPase activity of rat heart microsomes and mitochondria as well as on myofibrillar ATPase activity were investigated. Chloroform and halothane depressed microsomal and mitochondrial calcium uptake and binding in a parallel fashion. Ether decreased microsomal calcium binding and mitochondrial calcium uptake to varying degrees, while mitochondrial calcium binding was slightly enhanced. Whereas ether had no effect, chloroform depressed microsomal and mitochondrial total APTase activities and halothane decreased microsomsl ATPase and slightly stimulated mitochondrial total ATPase activities. Halothane was found to depress myofibrillar Mg2+-ATPase and ether was capable of decreasing myofibrillar Ca2+-ATPase. Chloroform was seen to inhibit both myofibrillar enzymes. These results suggest that the cardiodepressant actions of volatile anesthetic agents may be due to alterations in the calcium accumulating abilities of microsomal and mitochondrial membranes while direct myofibrillar effects may contribute to the depression seen with relatively higher concentrations of anesthetics.", "contents": "Subcellular effects of some anesthetic agents on rat myocardium. The effects of ether, chloroform, and halothane on calcium accumulation and ATPase activity of rat heart microsomes and mitochondria as well as on myofibrillar ATPase activity were investigated. Chloroform and halothane depressed microsomal and mitochondrial calcium uptake and binding in a parallel fashion. Ether decreased microsomal calcium binding and mitochondrial calcium uptake to varying degrees, while mitochondrial calcium binding was slightly enhanced. Whereas ether had no effect, chloroform depressed microsomal and mitochondrial total APTase activities and halothane decreased microsomsl ATPase and slightly stimulated mitochondrial total ATPase activities. Halothane was found to depress myofibrillar Mg2+-ATPase and ether was capable of decreasing myofibrillar Ca2+-ATPase. Chloroform was seen to inhibit both myofibrillar enzymes. These results suggest that the cardiodepressant actions of volatile anesthetic agents may be due to alterations in the calcium accumulating abilities of microsomal and mitochondrial membranes while direct myofibrillar effects may contribute to the depression seen with relatively higher concentrations of anesthetics."} {"id": "PMID:154967", "title": "Parathyroid adenomas following irradiation.", "content": "Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally.", "contents": "Parathyroid adenomas following irradiation. Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally."} {"id": "PMID:154968", "title": "Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long-term treatment with dehydroepiandrosterone.", "content": "Long-term p.o. treatment with dehydroepiandrosterone, an adrenal steroid found in subnormal plasma concentrations in women predisposed to develop breast cancer, inhibits the formation of spontaneous mammary cancer in female C3H(Avy/a) mice.", "contents": "Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long-term treatment with dehydroepiandrosterone. Long-term p.o. treatment with dehydroepiandrosterone, an adrenal steroid found in subnormal plasma concentrations in women predisposed to develop breast cancer, inhibits the formation of spontaneous mammary cancer in female C3H(Avy/a) mice."} {"id": "PMID:154970", "title": "Mutation induction by 5-fluorodeoxyuridine in synchronous Chinese hamster cells.", "content": "Chinese hamster ovary cells synchronized by mitotic detachment were treated with 5-fluorodeoxyuridine (FdUrd), 0.2 micrograms/ml, at various times in the cell cycle. FdUrd treatment in the early S period induced resistance to 6-thioguanine. Treatment of asynchronous cells with FdUrd caused little increase in 6-thioguanine resistance over the spontaneous frequency. Mitotic selection thus enhances the probability of a cell being in the portion of S period receptive to mutation. These observations suggest that FdUrd treatment leads to mutagenesis at the growing points of DNA replication.", "contents": "Mutation induction by 5-fluorodeoxyuridine in synchronous Chinese hamster cells. Chinese hamster ovary cells synchronized by mitotic detachment were treated with 5-fluorodeoxyuridine (FdUrd), 0.2 micrograms/ml, at various times in the cell cycle. FdUrd treatment in the early S period induced resistance to 6-thioguanine. Treatment of asynchronous cells with FdUrd caused little increase in 6-thioguanine resistance over the spontaneous frequency. Mitotic selection thus enhances the probability of a cell being in the portion of S period receptive to mutation. These observations suggest that FdUrd treatment leads to mutagenesis at the growing points of DNA replication."} {"id": "PMID:154971", "title": "Mediated mutagenesis of dimethylnitrosamine in Neurospora crassa by various metabolic activation systems.", "content": "Four metabolic activation systems (growth mediated mycelium extract mediated, host mediated, and organ homogenate mediated) were used to study the mutagenic activity of dimethylnitrosamine (DMN) in both forward and reverse mutation systems in the ad-3 (adenine-3) region of Neurospora crassa. DMN was not mutagenic in Neurospora if conidia alone were treated. It was highly mutagenic, however, if conidia were treated with this compound under any of the four activation systems. Quantitative differences in DMN-induced mutation frequencies were observed between in vivo (growth and host mediated) and in vitro (mycelium extract and organ homogenate mediated) activations. The efficiency of the conversion of DMN to a mutagenic metabolite by the organs of rats and mice appeared to be in a reversed order between the host-mediated (liver greater than kidney greater than lung) and the in vitro organ homogenate-mediated (lung greater than kidney greater than liver) assays. Inductions of reverse mutations in strain N23 indicated that DMN induces base-pair substitution in N. crassa.", "contents": "Mediated mutagenesis of dimethylnitrosamine in Neurospora crassa by various metabolic activation systems. Four metabolic activation systems (growth mediated mycelium extract mediated, host mediated, and organ homogenate mediated) were used to study the mutagenic activity of dimethylnitrosamine (DMN) in both forward and reverse mutation systems in the ad-3 (adenine-3) region of Neurospora crassa. DMN was not mutagenic in Neurospora if conidia alone were treated. It was highly mutagenic, however, if conidia were treated with this compound under any of the four activation systems. Quantitative differences in DMN-induced mutation frequencies were observed between in vivo (growth and host mediated) and in vitro (mycelium extract and organ homogenate mediated) activations. The efficiency of the conversion of DMN to a mutagenic metabolite by the organs of rats and mice appeared to be in a reversed order between the host-mediated (liver greater than kidney greater than lung) and the in vitro organ homogenate-mediated (lung greater than kidney greater than liver) assays. Inductions of reverse mutations in strain N23 indicated that DMN induces base-pair substitution in N. crassa."} {"id": "PMID:154973", "title": "Enhancement by caffeine of neocarzinostatin cytotoxicity in murine leukemia L1210 cells.", "content": "Posttreatment incubation with nontoxic doses of caffeine resulted in enhancement of cell lethality and inhibition of cell growth in L1210 mouse leukemia cells which had been exposed to a protein antibiotic, neocarzinostatin. In addition, caffeine treatment appeared to inhibit the eventual maturation of newly synthesized DNA in L1210 cells following exposure to this antibiotic. These results, indicating the existence of caffeine-sensitive repair in L1210 leukemia cells treated with neocarzinostatin, provide further evidence for DNA damage as a mechanism of the cytocidal action of the antibiotic.", "contents": "Enhancement by caffeine of neocarzinostatin cytotoxicity in murine leukemia L1210 cells. Posttreatment incubation with nontoxic doses of caffeine resulted in enhancement of cell lethality and inhibition of cell growth in L1210 mouse leukemia cells which had been exposed to a protein antibiotic, neocarzinostatin. In addition, caffeine treatment appeared to inhibit the eventual maturation of newly synthesized DNA in L1210 cells following exposure to this antibiotic. These results, indicating the existence of caffeine-sensitive repair in L1210 leukemia cells treated with neocarzinostatin, provide further evidence for DNA damage as a mechanism of the cytocidal action of the antibiotic."} {"id": "PMID:154980", "title": "The role of left ventricular conduction in the electrogenesis of left ventricular hypertrophy. An electrophysiologic study in man.", "content": "Various electrocardiographic and vectorcardiographic (ECG-VCG) patterns of ventricular conduction disturbances are inducible by premature right atrial stimulation (PRAS). These patterns are a consequence of different degrees of refractoriness in the specialized ventricular conduction system. We observed that the intermediate phase of left bundle branch block (LBBB) induced by PRAS in 20 subjects with normal basal QRS (complexes) were similar to those of left ventricular hypertrophy (LVH). In 18 patients with basal ECG-VCG signs of LVH, right bundle branch block (RBBB) induced by PRAS produced a progressive disappearance of these signs and the \"normalization\" of the tracings. The initial maximum QRS vector decreased, disappeared or remained absent in the patients with LBBB induced by PRAS, and appeared (when absent in the basal VCG) and remained unchanged (when present) in patients with RBBB induced by PRAS. In this paper we discuss the electrogenetic implications of these data. The ECG-VCG sings of LVH are probably dependent on a slowed conduction in the left bundle branch system, while anatomical hypertrophy per se probably plays a less important role.", "contents": "The role of left ventricular conduction in the electrogenesis of left ventricular hypertrophy. An electrophysiologic study in man. Various electrocardiographic and vectorcardiographic (ECG-VCG) patterns of ventricular conduction disturbances are inducible by premature right atrial stimulation (PRAS). These patterns are a consequence of different degrees of refractoriness in the specialized ventricular conduction system. We observed that the intermediate phase of left bundle branch block (LBBB) induced by PRAS in 20 subjects with normal basal QRS (complexes) were similar to those of left ventricular hypertrophy (LVH). In 18 patients with basal ECG-VCG signs of LVH, right bundle branch block (RBBB) induced by PRAS produced a progressive disappearance of these signs and the \"normalization\" of the tracings. The initial maximum QRS vector decreased, disappeared or remained absent in the patients with LBBB induced by PRAS, and appeared (when absent in the basal VCG) and remained unchanged (when present) in patients with RBBB induced by PRAS. In this paper we discuss the electrogenetic implications of these data. The ECG-VCG sings of LVH are probably dependent on a slowed conduction in the left bundle branch system, while anatomical hypertrophy per se probably plays a less important role."} {"id": "PMID:154981", "title": "Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy.", "content": "Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring had revealed ventricular tachycardia. Two patients with paroxysms of supraventricular tachycardia during monitoring developed fixed atrial fibrillation within 1 year. These preliminary observations suggest that monitoring may help identify patients at increased risk for significant arrhythmic events.", "contents": "Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy. Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring had revealed ventricular tachycardia. Two patients with paroxysms of supraventricular tachycardia during monitoring developed fixed atrial fibrillation within 1 year. These preliminary observations suggest that monitoring may help identify patients at increased risk for significant arrhythmic events."} {"id": "PMID:154982", "title": "Suppression of lymphoproliferative responses to alloantigens by autologous AML cells.", "content": "Autologous acute myeloid leukaemia (AML), cells caused the suppression of incorporation of 3H-thymidine (3H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous AML cells suppressed 3H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AML cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AML cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of less than 1:1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring AML cells into contact with circulating T cells in vivo. Autologous AML cells seem to interfere with the recognition phase of T cell function.", "contents": "Suppression of lymphoproliferative responses to alloantigens by autologous AML cells. Autologous acute myeloid leukaemia (AML), cells caused the suppression of incorporation of 3H-thymidine (3H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous AML cells suppressed 3H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AML cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AML cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of less than 1:1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring AML cells into contact with circulating T cells in vivo. Autologous AML cells seem to interfere with the recognition phase of T cell function."} {"id": "PMID:154983", "title": "Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus.", "content": "Peripheral blood mononuclear cells (PBM) obtained from patients with active untreated systemic lupus erythematosus (SLE) were evaluated both for the number of cells spontaneously secreting immunoglobulin (Ig) as well as for their capacity to generate immunoglobulin-secreting cells (ISC) in vitro in response to pokeweed mitogen (PWM). ISC were enumerated by a reverse haemolytic plaque assay designed to quantify the number of cells secreting IgG, IgM and IgA. PBM obtained from eight patients with active untreated SLE contained markedly increased numbers of ISC compared to age-, sex-, and race-matched normal control PBM. SLE PBM contained a mean of 13,805 +/- 3266 ISC per 10(6) cells, of which 74% secreted IgG, 10% IgM and 22% IgA, while normal PBM contained a mean of 779 +/- 143 ISC per 10(6) cells, with 57% secreting IgG, 25% IgM and 33% IgA. PBM obtained from SLE patients were also examined for their ability to generate ISC in vitro in response to PWM. SLE PBM were markedly deficient in their capacity to respond to PWM with the differentiation of ISC. This diminished responsiveness could not be ascribed to serum factors, the presence of increased numbers of cells with suppressive capacity or the absence of potentially responsive B cells. Rather, a deficiency of helper T cell activity appeared to be responsible. This was indicated by the observation that PWM responsiveness could be restored to SLE PBM by co-culturing them with purified mitomycin C-treated normal T cells.", "contents": "Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus. Peripheral blood mononuclear cells (PBM) obtained from patients with active untreated systemic lupus erythematosus (SLE) were evaluated both for the number of cells spontaneously secreting immunoglobulin (Ig) as well as for their capacity to generate immunoglobulin-secreting cells (ISC) in vitro in response to pokeweed mitogen (PWM). ISC were enumerated by a reverse haemolytic plaque assay designed to quantify the number of cells secreting IgG, IgM and IgA. PBM obtained from eight patients with active untreated SLE contained markedly increased numbers of ISC compared to age-, sex-, and race-matched normal control PBM. SLE PBM contained a mean of 13,805 +/- 3266 ISC per 10(6) cells, of which 74% secreted IgG, 10% IgM and 22% IgA, while normal PBM contained a mean of 779 +/- 143 ISC per 10(6) cells, with 57% secreting IgG, 25% IgM and 33% IgA. PBM obtained from SLE patients were also examined for their ability to generate ISC in vitro in response to PWM. SLE PBM were markedly deficient in their capacity to respond to PWM with the differentiation of ISC. This diminished responsiveness could not be ascribed to serum factors, the presence of increased numbers of cells with suppressive capacity or the absence of potentially responsive B cells. Rather, a deficiency of helper T cell activity appeared to be responsible. This was indicated by the observation that PWM responsiveness could be restored to SLE PBM by co-culturing them with purified mitomycin C-treated normal T cells."} {"id": "PMID:154984", "title": "Differences in the constitution and distribution of acidic glycosaminoglycans in the intimal and adventitial layers of bovine aorta.", "content": "Differences in the constitution of acidic glycosaminoglycans (AGAG) in the intimal layer and in the adventitia of bovine aorta were demonstrated by means of enzymatic assay and electrophoretic characterization after fractionation by ion-exchange chromatography and by gel filtration. The data obtained after ion-exchange chromatography indicated that chondroitin 4-sulfate and chondroitin 6-sulfate were the predominant constituents in the intima, whereas hyaluronic acid, dermatan sulfate, oversulfated dermatan sulfate, and heparan sulfates and a related glucosaminoglycan were the predominant constituents in the adventitia. The molecular weight dependent distribution of the aortic AGAG by gel filtration indicated that hyaluronic acid was prevalent in the high molecular weight fractions from both layers whereas chondroitin, heparan sulfates and the related glucosaminoglycan were present in the low molecular weight fraction, especially in adventitial AGAG. Chondroitin sulfate isomers, dermatan sulfate and oversulfated dermatan sulfate were distributed almost equally in all fractions, but the proportions were different in the two layers.", "contents": "Differences in the constitution and distribution of acidic glycosaminoglycans in the intimal and adventitial layers of bovine aorta. Differences in the constitution of acidic glycosaminoglycans (AGAG) in the intimal layer and in the adventitia of bovine aorta were demonstrated by means of enzymatic assay and electrophoretic characterization after fractionation by ion-exchange chromatography and by gel filtration. The data obtained after ion-exchange chromatography indicated that chondroitin 4-sulfate and chondroitin 6-sulfate were the predominant constituents in the intima, whereas hyaluronic acid, dermatan sulfate, oversulfated dermatan sulfate, and heparan sulfates and a related glucosaminoglycan were the predominant constituents in the adventitia. The molecular weight dependent distribution of the aortic AGAG by gel filtration indicated that hyaluronic acid was prevalent in the high molecular weight fractions from both layers whereas chondroitin, heparan sulfates and the related glucosaminoglycan were present in the low molecular weight fraction, especially in adventitial AGAG. Chondroitin sulfate isomers, dermatan sulfate and oversulfated dermatan sulfate were distributed almost equally in all fractions, but the proportions were different in the two layers."} {"id": "PMID:154985", "title": "A comparative study of two isolation procedures for elastin and contaminating substances in fetal and adult rabbit aortas.", "content": "A quantitative study of the individual steps in the isolation of elastin from mature and fetal aortas of rabbits was carried out. The proportions of insoluble residue and acetone- and ether-soluble substances were determined. The yields of elastin and other associated components of connective tissue derived from the aortas by two different isolation procedures were compared, i.e. the classical Lansing treatment with hot alkali and the less drastic procedure described by Rasmussen et al. Results were found to be strongly influenced by the method used. The purity of the elastin preparations was evaluated by means of amino acid analyses for relative contents of desmosines and dicarboxylic amino acids. The possible reasons for the differences found are discussed.", "contents": "A comparative study of two isolation procedures for elastin and contaminating substances in fetal and adult rabbit aortas. A quantitative study of the individual steps in the isolation of elastin from mature and fetal aortas of rabbits was carried out. The proportions of insoluble residue and acetone- and ether-soluble substances were determined. The yields of elastin and other associated components of connective tissue derived from the aortas by two different isolation procedures were compared, i.e. the classical Lansing treatment with hot alkali and the less drastic procedure described by Rasmussen et al. Results were found to be strongly influenced by the method used. The purity of the elastin preparations was evaluated by means of amino acid analyses for relative contents of desmosines and dicarboxylic amino acids. The possible reasons for the differences found are discussed."} {"id": "PMID:154987", "title": "Dependence of collagen synthesis by embryonic chick tendon cells on the extracellular concentrations of glutamine.", "content": "An agent in rheumatoid synovial fluid which stimulates collagen synthesis by embryonic chick tendon cells was identified as glutamine. The stimulating effect was observed only at a subnormal concentration of proline (0.02 mM). The concentration of glutamine in rheumatoid synovial fluid is about 2.5 mM but it falls rapidly during storage even at -20 degrees C. Collagen synthesis is shown to depend on the extracellular concentrations of glutamine and proline in addition to any connective tissue activating factors.", "contents": "Dependence of collagen synthesis by embryonic chick tendon cells on the extracellular concentrations of glutamine. An agent in rheumatoid synovial fluid which stimulates collagen synthesis by embryonic chick tendon cells was identified as glutamine. The stimulating effect was observed only at a subnormal concentration of proline (0.02 mM). The concentration of glutamine in rheumatoid synovial fluid is about 2.5 mM but it falls rapidly during storage even at -20 degrees C. Collagen synthesis is shown to depend on the extracellular concentrations of glutamine and proline in addition to any connective tissue activating factors."} {"id": "PMID:154988", "title": "Influence of maturation and age on mechanical and biochemical parameters of connective tissue of various organs in the rat.", "content": "The mechanical and biochemical parameters of connective tissue components of several organs in rats, e.g. skin, tail tendons and aorta, have been compared. Organ samples have been analyzed at various ages allowing investigation of the changes during maturation and senescence. The age dependent changes in the various organs were quite similar. The parameters indicating strength and elasticity, e.g. ultimate load, ultimate strength, ultimate strain, modulus of elasticity and rate of load increase, rose sharply during the maturation process and decreased during senescence. These values correlated with changes in insoluble collagen but not with those in elastin or glycosaminoglycans as shown in earlier experiments. The relevance of mechanical models to explain age-dependent changes as compared to descriptive correlations between mechanical and biochemical data is discussed.", "contents": "Influence of maturation and age on mechanical and biochemical parameters of connective tissue of various organs in the rat. The mechanical and biochemical parameters of connective tissue components of several organs in rats, e.g. skin, tail tendons and aorta, have been compared. Organ samples have been analyzed at various ages allowing investigation of the changes during maturation and senescence. The age dependent changes in the various organs were quite similar. The parameters indicating strength and elasticity, e.g. ultimate load, ultimate strength, ultimate strain, modulus of elasticity and rate of load increase, rose sharply during the maturation process and decreased during senescence. These values correlated with changes in insoluble collagen but not with those in elastin or glycosaminoglycans as shown in earlier experiments. The relevance of mechanical models to explain age-dependent changes as compared to descriptive correlations between mechanical and biochemical data is discussed."} {"id": "PMID:154989", "title": "Explant culture of human and rabbit articular chondrocytes.", "content": "Copious outgrowth of chondrocytes was obtained by explantation from each of three rabbit and one surgically-resected human articular cartilages pretreated briefly with trypsin. In lapine explants, ascorbate (40 micrograms/ml) increased DNA three-fold over control values and resulted in deposition of a chondroid matrix. It doubled radiosulfate incorporation by the outgrowths. Up to 56% of the sulfated glycosaminoglycan synthesized was located in the trypsin-digestible pericellular coat compared with about 15% in previous monolayer cultures. The collagens synthesized were characterized partially. In rabbit cell cultures, the alpha 1:alpha 2 ratio varied from 2.9 to 3.8. In human cultures, an unusual post-alpha 2 peak was observed. The findings suggest an uncoupling of the phenotypic expression of the major cartilaginous macromolecules in the cultures. There were no distinctive differences between chondrocytes derived from normal and fibrillated human cartilage of the same individual.", "contents": "Explant culture of human and rabbit articular chondrocytes. Copious outgrowth of chondrocytes was obtained by explantation from each of three rabbit and one surgically-resected human articular cartilages pretreated briefly with trypsin. In lapine explants, ascorbate (40 micrograms/ml) increased DNA three-fold over control values and resulted in deposition of a chondroid matrix. It doubled radiosulfate incorporation by the outgrowths. Up to 56% of the sulfated glycosaminoglycan synthesized was located in the trypsin-digestible pericellular coat compared with about 15% in previous monolayer cultures. The collagens synthesized were characterized partially. In rabbit cell cultures, the alpha 1:alpha 2 ratio varied from 2.9 to 3.8. In human cultures, an unusual post-alpha 2 peak was observed. The findings suggest an uncoupling of the phenotypic expression of the major cartilaginous macromolecules in the cultures. There were no distinctive differences between chondrocytes derived from normal and fibrillated human cartilage of the same individual."} {"id": "PMID:154990", "title": "Generation of Hall voltage in bone.", "content": "Hall type voltage has been observed in bone and its two major components (collagen and apatite) in the region of moderately high electric and magnetic fields. The configuration of the sample placement and the experimental set up was the same as that adopted in standard Hall measurements. The resistivity of the sample has been related to the Hall Coefficients through the standard relationship and an estimate of Hall mobility was made. The Hall Coefficients were found to be of the order of 10(6) cm3 col-1 while the Hall mobility generally was in the region of less than 1 cm2/volt sec. A comparison with drift mobility suggests that the latter is at least two to three orders of magnitude less than the former. A possible mechanism underlying the said transport phenomena is discussed.", "contents": "Generation of Hall voltage in bone. Hall type voltage has been observed in bone and its two major components (collagen and apatite) in the region of moderately high electric and magnetic fields. The configuration of the sample placement and the experimental set up was the same as that adopted in standard Hall measurements. The resistivity of the sample has been related to the Hall Coefficients through the standard relationship and an estimate of Hall mobility was made. The Hall Coefficients were found to be of the order of 10(6) cm3 col-1 while the Hall mobility generally was in the region of less than 1 cm2/volt sec. A comparison with drift mobility suggests that the latter is at least two to three orders of magnitude less than the former. A possible mechanism underlying the said transport phenomena is discussed."} {"id": "PMID:154991", "title": "Proteogylcan heterogeneity in embryonic chick articular and epiphyseal cartilages.", "content": "Proteoglycans from two regions of the chick limb rudiment (articular and epiphyseal) were examined for chemical microheterogeneity. These cartilages are composed of at least two series of proteoglycan variants whose glycosaminoglycan side chains display microheterogeneity with respect to the proportions of 4- and 6-linked ester sulfate. Other differences are noted which are consonant with the hypothesis that extracellular matrix components may be structurally adapted to a tissue's developmental fate or function.", "contents": "Proteogylcan heterogeneity in embryonic chick articular and epiphyseal cartilages. Proteoglycans from two regions of the chick limb rudiment (articular and epiphyseal) were examined for chemical microheterogeneity. These cartilages are composed of at least two series of proteoglycan variants whose glycosaminoglycan side chains display microheterogeneity with respect to the proportions of 4- and 6-linked ester sulfate. Other differences are noted which are consonant with the hypothesis that extracellular matrix components may be structurally adapted to a tissue's developmental fate or function."} {"id": "PMID:154992", "title": "Functional differentiation of various types of cardiomyopathies by echocardiography.", "content": "Echocardiography was used to compare the left ventricular function in 35 cases of congestive cardiomyopathy (COCM), 16 cases of obstructive and 28 cases of non-obstructive asymmetric septal hypertrophy, 43 cases of scleroderma heart disease, 21 cases of ischaemic cardiomyopathy (ICM), 2 cases of restrictive cardiomyopathy, and one case of cardiac amyloidosis. COCM was characterized by left ventricular dilatation, decreased contractility and signs of elevated end-diastolic pressure. In asymmetric septal hypertrophy there was a decreased distensibility of the obstructed left ventricle, both in early and end-diastole, but the pump function remained normal. In scleroderma and amyloid heart disease both the contractility and distensibility of the small, stiff heart were reduced. In restrictive cardiomyopathy the only abnormality was the impaired end-diastolic distensibility. Reduced contractility confined primarily to the interventricular septum and impaired early diastolic distensibility are the characteristic features distinguishing ischaemic cardiomyopathy from COCM. However, echocardiography is not suitable for individual differentiation of ICM and COCM. The COCM can be differentiated from left ventricular aneurysm by M-mode sector scanning technique.", "contents": "Functional differentiation of various types of cardiomyopathies by echocardiography. Echocardiography was used to compare the left ventricular function in 35 cases of congestive cardiomyopathy (COCM), 16 cases of obstructive and 28 cases of non-obstructive asymmetric septal hypertrophy, 43 cases of scleroderma heart disease, 21 cases of ischaemic cardiomyopathy (ICM), 2 cases of restrictive cardiomyopathy, and one case of cardiac amyloidosis. COCM was characterized by left ventricular dilatation, decreased contractility and signs of elevated end-diastolic pressure. In asymmetric septal hypertrophy there was a decreased distensibility of the obstructed left ventricle, both in early and end-diastole, but the pump function remained normal. In scleroderma and amyloid heart disease both the contractility and distensibility of the small, stiff heart were reduced. In restrictive cardiomyopathy the only abnormality was the impaired end-diastolic distensibility. Reduced contractility confined primarily to the interventricular septum and impaired early diastolic distensibility are the characteristic features distinguishing ischaemic cardiomyopathy from COCM. However, echocardiography is not suitable for individual differentiation of ICM and COCM. The COCM can be differentiated from left ventricular aneurysm by M-mode sector scanning technique."} {"id": "PMID:154994", "title": "Kyrle's disease.", "content": "A fifty-nine year old man is reported herein with a hyperkeratotic papular eruption that clinically and histologically was compatible with Kyrle's disease (hyperkeratosis follicularis et parafollicularis in cutem penetrans). Treatment with tretinoin (topical vitamine A acid) resulted in a severe inflammatory reactions in the lesions which persisted for four monthes and did not prevent a mild recurrence of the disease. The clinical and histologic differential diagnosis is reviewed perforating folliculitis, reactive perforating collagenosis, and elastosis perforans serpiginosa. The close similarity between Kyrle's disease and perforating folliculitis often makes absolute diagnosis very difficult.", "contents": "Kyrle's disease. A fifty-nine year old man is reported herein with a hyperkeratotic papular eruption that clinically and histologically was compatible with Kyrle's disease (hyperkeratosis follicularis et parafollicularis in cutem penetrans). Treatment with tretinoin (topical vitamine A acid) resulted in a severe inflammatory reactions in the lesions which persisted for four monthes and did not prevent a mild recurrence of the disease. The clinical and histologic differential diagnosis is reviewed perforating folliculitis, reactive perforating collagenosis, and elastosis perforans serpiginosa. The close similarity between Kyrle's disease and perforating folliculitis often makes absolute diagnosis very difficult."} {"id": "PMID:154995", "title": "Adverse effects of corticosteroids.", "content": "The introduction of corticosteroids has constitutded the most revolutionary event in dermatologic therapy in the last twenty-five years. The effectiveness of topical therapy in well diagnosed and obscure dermatoses led to wide applications by specialists and general practitioners, and resulted in the development of more potent topical steroid preparations. Their enthusiastic acceptance, and often indiscriminante use, has been followed by occasional reports of adverse effects. After the introduction of occlusive topical steroid therapy under plastic wrap, more dramatic therapeutic effects were achieved, but the adverse effects also increased. There is presently an abundance of reports elaborating on systemic and local adverse reactions resulting from topically applied or intralesionally injected steroids. This report summarizes the local side effects of these steroids.", "contents": "Adverse effects of corticosteroids. The introduction of corticosteroids has constitutded the most revolutionary event in dermatologic therapy in the last twenty-five years. The effectiveness of topical therapy in well diagnosed and obscure dermatoses led to wide applications by specialists and general practitioners, and resulted in the development of more potent topical steroid preparations. Their enthusiastic acceptance, and often indiscriminante use, has been followed by occasional reports of adverse effects. After the introduction of occlusive topical steroid therapy under plastic wrap, more dramatic therapeutic effects were achieved, but the adverse effects also increased. There is presently an abundance of reports elaborating on systemic and local adverse reactions resulting from topically applied or intralesionally injected steroids. This report summarizes the local side effects of these steroids."} {"id": "PMID:154996", "title": "Healing of recalcitrant acne by resting the skin.", "content": "A rest treatment for recalcitrant acne in a patient with acne of ten years' duration is presented herein.", "contents": "Healing of recalcitrant acne by resting the skin. A rest treatment for recalcitrant acne in a patient with acne of ten years' duration is presented herein."} {"id": "PMID:154997", "title": "Idiopathic portal hypertension and chronic arsenic poisoning. Report of a case.", "content": "We report a case of idiopathic portal hypertension which is related to chronic arsenic poisoning. Only 7 cases have been reported previously. The patient presented with bleeding esophageal varices. Splenomegaly and hyperkeratosis of palms and soles were later noted and led to the discovery of chronic arsenic poisoning. The hemodynamic studies revealed a gradient between the splenic pulp pressure and hepatic wedge pressure which is consistent with presinusoidal hypertension. The liver histology revealed only mild portal fibrosis. Arsenic poisoning is one cause of idiopathic protal hypertension.", "contents": "Idiopathic portal hypertension and chronic arsenic poisoning. Report of a case. We report a case of idiopathic portal hypertension which is related to chronic arsenic poisoning. Only 7 cases have been reported previously. The patient presented with bleeding esophageal varices. Splenomegaly and hyperkeratosis of palms and soles were later noted and led to the discovery of chronic arsenic poisoning. The hemodynamic studies revealed a gradient between the splenic pulp pressure and hepatic wedge pressure which is consistent with presinusoidal hypertension. The liver histology revealed only mild portal fibrosis. Arsenic poisoning is one cause of idiopathic protal hypertension."} {"id": "PMID:154998", "title": "Laparoscopic diagnosis of peritoneal mesothelioma. Report of a case and review of the diagnostic approach.", "content": "This is the second report of a malignant peritoneal mesothelioma diagnosed by laparoscopy and guided needle biopsy and the first with photographic documentation of the lesion. The case illustrates the following points: (1) diagnosis of peritoneal mesothelioma should be considered in the evaluation of exudative ascites; (2) the only definitive diagnostic procedure is to obtain tissue for histology; and (3) laparoscopy with biopsies under direct vision is an accurate and safe technique which is underutilized and should be considered as the diagnostic procedure of choice when peritoneal disease is suspected.", "contents": "Laparoscopic diagnosis of peritoneal mesothelioma. Report of a case and review of the diagnostic approach. This is the second report of a malignant peritoneal mesothelioma diagnosed by laparoscopy and guided needle biopsy and the first with photographic documentation of the lesion. The case illustrates the following points: (1) diagnosis of peritoneal mesothelioma should be considered in the evaluation of exudative ascites; (2) the only definitive diagnostic procedure is to obtain tissue for histology; and (3) laparoscopy with biopsies under direct vision is an accurate and safe technique which is underutilized and should be considered as the diagnostic procedure of choice when peritoneal disease is suspected."} {"id": "PMID:154999", "title": "[Attempt of a definite statement on dental care for the handicapped].", "content": "A survey made in cooperation with various institutions for the handicapped ascertained the dental coverage and care of the handicapped. Participating in the survey were 634 institutions for the handicapped. The study included 98,737 handicapped individuals treated on both an in-patient and an out-patient basis in these institutions. The results of the survey tend to indicate that dental care for the handicapped is in need of improvement.", "contents": "[Attempt of a definite statement on dental care for the handicapped]. A survey made in cooperation with various institutions for the handicapped ascertained the dental coverage and care of the handicapped. Participating in the survey were 634 institutions for the handicapped. The study included 98,737 handicapped individuals treated on both an in-patient and an out-patient basis in these institutions. The results of the survey tend to indicate that dental care for the handicapped is in need of improvement."} {"id": "PMID:155004", "title": "Impairment of olfactory perception in male rats by treatment with p-chlorophenylalanine and hydrocortisone.", "content": "p-Chlorophenylalanine treatment eliminated the normal male rat preference for the female preputial gland odor. Oral administration of hydrocortisone had a similar effect on dimethyl sulfite preference, which slowly reappeared after the discontinuance of the treatment. These changes of behavior are discussed in relation to possible serotonin alterations resulting from the treatments.", "contents": "Impairment of olfactory perception in male rats by treatment with p-chlorophenylalanine and hydrocortisone. p-Chlorophenylalanine treatment eliminated the normal male rat preference for the female preputial gland odor. Oral administration of hydrocortisone had a similar effect on dimethyl sulfite preference, which slowly reappeared after the discontinuance of the treatment. These changes of behavior are discussed in relation to possible serotonin alterations resulting from the treatments."} {"id": "PMID:155005", "title": "Adrenarche: a survey of rodents, domestic animals, and primates.", "content": "The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man.", "contents": "Adrenarche: a survey of rodents, domestic animals, and primates. The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man."} {"id": "PMID:155006", "title": "Formation of steroids by the pregnant mare. VI. Metabolism of [14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone injected into the fetus.", "content": "A mixture of [4,8,12-14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone was injected into a horse fetus im during laparotomy, after which maternal urine was collected for 6 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolyzed, and separated into phenolic and neutral fractions. Estrone, 17 alpha-estradiol, equilin [3-hydroxy-1,3,5(10),7-estratetraen-17-one], and 17 alpha-dihydroequilin [1,3,4(10),7-estratetraene-3,17 alpha-diol] were isolated from the phenolic fraction and their radiochemical purities were established. Only estrone and 17 alpha-estradiol contained both 3H and 14C, while the B ring unsaturated estrogens, equilin and 17 alpha-dihydroequilin, contained only 14C. From the neutral fraction, 14C-labeled 3 beta-hydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3 beta-20 beta-diol, and 5 alpha-pregnane-3 beta, 20 alpha-diol were isolated. These results together with our previous findings demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of farnesyl pyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis is occurring at a point after the formation of farnesyl pyrophosphate and before the formation of squalene and cholesterol.", "contents": "Formation of steroids by the pregnant mare. VI. Metabolism of [14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone injected into the fetus. A mixture of [4,8,12-14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone was injected into a horse fetus im during laparotomy, after which maternal urine was collected for 6 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolyzed, and separated into phenolic and neutral fractions. Estrone, 17 alpha-estradiol, equilin [3-hydroxy-1,3,5(10),7-estratetraen-17-one], and 17 alpha-dihydroequilin [1,3,4(10),7-estratetraene-3,17 alpha-diol] were isolated from the phenolic fraction and their radiochemical purities were established. Only estrone and 17 alpha-estradiol contained both 3H and 14C, while the B ring unsaturated estrogens, equilin and 17 alpha-dihydroequilin, contained only 14C. From the neutral fraction, 14C-labeled 3 beta-hydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3 beta-20 beta-diol, and 5 alpha-pregnane-3 beta, 20 alpha-diol were isolated. These results together with our previous findings demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of farnesyl pyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis is occurring at a point after the formation of farnesyl pyrophosphate and before the formation of squalene and cholesterol."} {"id": "PMID:155007", "title": "Systolic time intervals and echocardiographic findings in borderline hypertension.", "content": "Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases.", "contents": "Systolic time intervals and echocardiographic findings in borderline hypertension. Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases."} {"id": "PMID:155008", "title": "[Rearing of germfree rabbits and establishment of an SPF rabbit colony].", "content": "Baby rabbits hysterectomy-derived from conventional Japanese white rabbits were reared under aseptic condition by feeding with 4 types of artificial diets. Rabbit milk for the artificial diet was obtained from conventional dams at 7--25 days after delivery. The artificial diets was given by stomach tube twice a day. The total volumes of diet given (ml per day) were Y = 2.3X + a (1 to approximately 14 days of age), Y = 32.2 + a (l5 to approximately 25 days of age), or Y = (32.2 + a) - 37.5 (X - 25) (26 to approximately 34 days of age), (X = age in days, a = volumes fed at 0 day of age). After 14 days of age young animals were also fed freely sterilized commercial pellets and weaned at 35 days of age. Out of 155 rabbits, 130 were aseptically reared till 36 approximately 40 days of age, and no difference on weaning rate was seen between the 4 groups of rabbits. Thereafter, they were exposed to a barriered room of SPF rabbitry outside the isolators. The best growth was seen in animals given by artificial diet containing rabbit milk at 40%. The SPF breeding colony of rabbits was found to be free of Pasteurella pneumotropica, Bordetella bronchiseptica, Salmonella spp., Eimeria spp., Encephalitozoon cuniculi and Acaritic otistis.", "contents": "[Rearing of germfree rabbits and establishment of an SPF rabbit colony]. Baby rabbits hysterectomy-derived from conventional Japanese white rabbits were reared under aseptic condition by feeding with 4 types of artificial diets. Rabbit milk for the artificial diet was obtained from conventional dams at 7--25 days after delivery. The artificial diets was given by stomach tube twice a day. The total volumes of diet given (ml per day) were Y = 2.3X + a (1 to approximately 14 days of age), Y = 32.2 + a (l5 to approximately 25 days of age), or Y = (32.2 + a) - 37.5 (X - 25) (26 to approximately 34 days of age), (X = age in days, a = volumes fed at 0 day of age). After 14 days of age young animals were also fed freely sterilized commercial pellets and weaned at 35 days of age. Out of 155 rabbits, 130 were aseptically reared till 36 approximately 40 days of age, and no difference on weaning rate was seen between the 4 groups of rabbits. Thereafter, they were exposed to a barriered room of SPF rabbitry outside the isolators. The best growth was seen in animals given by artificial diet containing rabbit milk at 40%. The SPF breeding colony of rabbits was found to be free of Pasteurella pneumotropica, Bordetella bronchiseptica, Salmonella spp., Eimeria spp., Encephalitozoon cuniculi and Acaritic otistis."} {"id": "PMID:155009", "title": "[Rearing of germfree guinea pigs and establishment of an SPF guinea pig colony].", "content": "New born guinea pigs of Hartley strain derived by hysterectomy were fed commercial pellets, cow's milk, egg yolk and vitamin mixture since 0 days of age, when they were kept at 31 +/- 1 degrees C. Out of 33 animals, 30 were reared for 40 days under aseptic state and they were transfered to a barrierred facility to establish an SPF colony free from Bordetella bronchiseptica, Streptococcus zooepidemicus (Animal C), Salmonella spp., Tyzzer's organisms, Mycoplasma spp., Reo 3 virus, Sendai virus, Eimeria spp., Chirodiscoides caviae and Gliriocola porcelli.", "contents": "[Rearing of germfree guinea pigs and establishment of an SPF guinea pig colony]. New born guinea pigs of Hartley strain derived by hysterectomy were fed commercial pellets, cow's milk, egg yolk and vitamin mixture since 0 days of age, when they were kept at 31 +/- 1 degrees C. Out of 33 animals, 30 were reared for 40 days under aseptic state and they were transfered to a barrierred facility to establish an SPF colony free from Bordetella bronchiseptica, Streptococcus zooepidemicus (Animal C), Salmonella spp., Tyzzer's organisms, Mycoplasma spp., Reo 3 virus, Sendai virus, Eimeria spp., Chirodiscoides caviae and Gliriocola porcelli."} {"id": "PMID:155014", "title": "Reduced T cell reactivity in vasectomized rhesus monkeys: association with histocompatibility type.", "content": "The capacity of peripheral lymphocytes from rhesus monkeys which had been vasectomized for 7 or 11 years to stimulate and respond to normal rhesus lymphocytes in mixed lymphocyte cultures (MLC) was tested to determine whether vasectomy affects immunologic reactivity. The ability to respond in MLC, a T cell function, was significantly reduced in the 11-year vasectomized animals and in two 7-year vasectomized animals. The ability to stimulate in MLC, a B cell function, was significantly increased in the 11-year vasectomized group. MLC reactivity of normal lymphocytes cultured in plasma from vasectomized animals and lymphocytes from vasectomized animals cultured in normal plasma was not altered, ruling out serum effects in the reduction of MLC responsiveness in these vasectomized animals. Seventy-five per cent of the vasectomized animals with markedly reduced MLC reactivity had the RhL-A determinates 19 and 24, indicating an association between the tendency toward reduced MLC reactivity after vasectomy and histocompatibility type.", "contents": "Reduced T cell reactivity in vasectomized rhesus monkeys: association with histocompatibility type. The capacity of peripheral lymphocytes from rhesus monkeys which had been vasectomized for 7 or 11 years to stimulate and respond to normal rhesus lymphocytes in mixed lymphocyte cultures (MLC) was tested to determine whether vasectomy affects immunologic reactivity. The ability to respond in MLC, a T cell function, was significantly reduced in the 11-year vasectomized animals and in two 7-year vasectomized animals. The ability to stimulate in MLC, a B cell function, was significantly increased in the 11-year vasectomized group. MLC reactivity of normal lymphocytes cultured in plasma from vasectomized animals and lymphocytes from vasectomized animals cultured in normal plasma was not altered, ruling out serum effects in the reduction of MLC responsiveness in these vasectomized animals. Seventy-five per cent of the vasectomized animals with markedly reduced MLC reactivity had the RhL-A determinates 19 and 24, indicating an association between the tendency toward reduced MLC reactivity after vasectomy and histocompatibility type."} {"id": "PMID:155015", "title": "Is palmoplantar keratoderma of Greither's type a separate nosologic entity?", "content": "17 patients with palmoplantar keratoderma (PPK) were detected among 48 investigated members of the clan O. 5 of these 17 patients had a well-expressed hyperkeratosis on their knees. In one family hyperkeratosis of the knees was inherited as a dominant feature, but in two other families it was not. The observation was made that the expressivity of the disease was fading: while there were 15 PPK patients among the 25 investigated members in the generations II and III, there were only 2 patients among 22 members in the generations IV and V. In addition to PPK incontinentia pigmenti was diagnosed in two instances and pollex duplex in one. The question of the identity of PPK of Greither's type is shortly discussed.", "contents": "Is palmoplantar keratoderma of Greither's type a separate nosologic entity? 17 patients with palmoplantar keratoderma (PPK) were detected among 48 investigated members of the clan O. 5 of these 17 patients had a well-expressed hyperkeratosis on their knees. In one family hyperkeratosis of the knees was inherited as a dominant feature, but in two other families it was not. The observation was made that the expressivity of the disease was fading: while there were 15 PPK patients among the 25 investigated members in the generations II and III, there were only 2 patients among 22 members in the generations IV and V. In addition to PPK incontinentia pigmenti was diagnosed in two instances and pollex duplex in one. The question of the identity of PPK of Greither's type is shortly discussed."} {"id": "PMID:155016", "title": "Antibiotic sensitivity of gonococcal strains isolated from patients in Basel and environs.", "content": "During the first 4 months of 1977, 95 different strains of gonococcus were isolated in the out-patient department of the Dermatology Clinic of the University of Basel. These were systemically tested for sensitivity to penicillin G, spectinomycin, thiamphenicol, doxycycline and rifampicin. The MIC values and the diameter of the zones of inhibition were determined. Tests for beta-lactamase production were made. A correlation in the degree of sensitivity was observed between the following antibiotics: penicillin G/rifampicin; penicillin G/thiamphenicol; penicillin G/doxycycline; thiamphenicol/doxycycline; thiamphenicol/rifampicin; doxycycline/rifampicin. The size of the inoculum had little influence on the activity of the substances, except for that of penicillin G against the beta-lactamase-positive reference strains. No beta-lactamase-producing strains were detected amongst the clinical isolates. In the case of penicillin G, there was a correlation between the minimum inhibitory concentration and the inhibition-zone diameter.", "contents": "Antibiotic sensitivity of gonococcal strains isolated from patients in Basel and environs. During the first 4 months of 1977, 95 different strains of gonococcus were isolated in the out-patient department of the Dermatology Clinic of the University of Basel. These were systemically tested for sensitivity to penicillin G, spectinomycin, thiamphenicol, doxycycline and rifampicin. The MIC values and the diameter of the zones of inhibition were determined. Tests for beta-lactamase production were made. A correlation in the degree of sensitivity was observed between the following antibiotics: penicillin G/rifampicin; penicillin G/thiamphenicol; penicillin G/doxycycline; thiamphenicol/doxycycline; thiamphenicol/rifampicin; doxycycline/rifampicin. The size of the inoculum had little influence on the activity of the substances, except for that of penicillin G against the beta-lactamase-positive reference strains. No beta-lactamase-producing strains were detected amongst the clinical isolates. In the case of penicillin G, there was a correlation between the minimum inhibitory concentration and the inhibition-zone diameter."} {"id": "PMID:155017", "title": "Comedo formation following cobalt irradiation.", "content": "After cobalt-60 therapy 3 patients developed open and closed comedones in the face corresponding to the treatment fields. Biopsies showed extensive dermal elastotic material. It is suggested that the elastotic fibres may contribute to a change in the supporting function of the dermis and a secondary sebum retention and comedo formation.", "contents": "Comedo formation following cobalt irradiation. After cobalt-60 therapy 3 patients developed open and closed comedones in the face corresponding to the treatment fields. Biopsies showed extensive dermal elastotic material. It is suggested that the elastotic fibres may contribute to a change in the supporting function of the dermis and a secondary sebum retention and comedo formation."} {"id": "PMID:155019", "title": "Laparoscopic finding of the gallbladder in a case of intramural gallstones.", "content": "In this 42-year-old-man with suspected cholelithiasis the following finding of the serosal surface of the gallbladder was discovered by laparoscopic examination: Smooth serosal elevation, dark-greenish in color in a size of the small bean; No hypervascularity in the surrounding serosa. This finding was confirmed to be due to intramural gallstones. This is the first description of the laparoscopic finding of the intramural stones of the gallbladder, which may assist in establishing the clinical characteristics of the intramural gallstones.", "contents": "Laparoscopic finding of the gallbladder in a case of intramural gallstones. In this 42-year-old-man with suspected cholelithiasis the following finding of the serosal surface of the gallbladder was discovered by laparoscopic examination: Smooth serosal elevation, dark-greenish in color in a size of the small bean; No hypervascularity in the surrounding serosa. This finding was confirmed to be due to intramural gallstones. This is the first description of the laparoscopic finding of the intramural stones of the gallbladder, which may assist in establishing the clinical characteristics of the intramural gallstones."} {"id": "PMID:155020", "title": "Fibrinolytic activity in gastric venous blood. A comparison between normal and diseased stomachs.", "content": "The fibrinolytic activity of blood draining from the stomachs of patients with gastroduodenal disease has been compared with the fibrinolytic activity of blood in the systemic venous circulation and with the blood draining from normal stomachs. Gastric venous blood from normal and diseased stomachs contains greater amounts of plasminogen activator than simultaneously sampled systemic venous blood. However, gastric venous fibrinolytic activity does not differ between the normal and diseased stomachs and thus indicates that increased gastric venous fibrinolysis is not just a characteristic of the diseased stomach. The studies suggest that stress may cause activation of the fibrinolytic system in gastric venous blood with the release of small amounts of free plasmin. It is postulated that local fibrinolysis may play a part in potentiating gastric hemorrhage.", "contents": "Fibrinolytic activity in gastric venous blood. A comparison between normal and diseased stomachs. The fibrinolytic activity of blood draining from the stomachs of patients with gastroduodenal disease has been compared with the fibrinolytic activity of blood in the systemic venous circulation and with the blood draining from normal stomachs. Gastric venous blood from normal and diseased stomachs contains greater amounts of plasminogen activator than simultaneously sampled systemic venous blood. However, gastric venous fibrinolytic activity does not differ between the normal and diseased stomachs and thus indicates that increased gastric venous fibrinolysis is not just a characteristic of the diseased stomach. The studies suggest that stress may cause activation of the fibrinolytic system in gastric venous blood with the release of small amounts of free plasmin. It is postulated that local fibrinolysis may play a part in potentiating gastric hemorrhage."} {"id": "PMID:155033", "title": "Origin of the extra chromosome in trisomy 21.", "content": "Of 61 families of children with trisomy 21, polymorphism of chromosome 21 elucidating the origin of the extra chromosome was found in 42. Nondisjunction was of paternal origin in 8 cases (19.04%) and the anomaly occurred with equal frequency during the first and second meiotic divisions. Maternal nondisjunction was demonstrated in 34 cases (80.95%), in which nondisjunction occurred by far the most often during the first meiotic division (29 cases). These results are in agreement with data from the literature, and suggest the existence of at least two different causes for chromosomal nondisjunction, the first being the same in both sexes and occurring in both meiotic divisions and the second specifically limited to the first meiotic division in the mother.", "contents": "Origin of the extra chromosome in trisomy 21. Of 61 families of children with trisomy 21, polymorphism of chromosome 21 elucidating the origin of the extra chromosome was found in 42. Nondisjunction was of paternal origin in 8 cases (19.04%) and the anomaly occurred with equal frequency during the first and second meiotic divisions. Maternal nondisjunction was demonstrated in 34 cases (80.95%), in which nondisjunction occurred by far the most often during the first meiotic division (29 cases). These results are in agreement with data from the literature, and suggest the existence of at least two different causes for chromosomal nondisjunction, the first being the same in both sexes and occurring in both meiotic divisions and the second specifically limited to the first meiotic division in the mother."} {"id": "PMID:155044", "title": "[Physical education for spina bifida children in special schools for the physically handicapped (primary school)].", "content": "With a rate of 0.5-1/1,000 of the total number of births in West Germany, spina bifida is next to cerebral paresis one of the most frequent congenital defects. Altogether, fifty places in special schools are needed per one million of inhabitants for spina bifida children. The loss of physical unctions is comparable to that in the case of paraplegia. The variety of medical and psychological problems makes the cooperation of highly different branches of study indispensible in a rehabilitation team (neurosurgeon, neuropediatrician, urologist, orthopaedist, pediatrician, educator, social worker, physical therapist). Each team member must be informed about the complete rehabilitation plan. These children's shortage of environmental experience is mainly due to their backwardness as regards motoric development, which cannot be recovered by means of individual physical therapy alone. On the other hand, additional, specifically selected and organised physical education makes possible the necessary mobility and social experiences. By giving the children exercises suitable for their ages it is hoped to achieve a late maturation and stabilization of the personality. In choosing the exercises it is first of all necessary to go back to the so-called fundamental activities like climbing, hanging by one's hands, sliding, pushing oneself up off the ground, swinging or throwing and catching, before going on to wheel-chair sports. Wheel-chair sport promises a varied selection for group exercises (games) and for everyday use. Using the wheel-chair as sports equipment, it is possible for persons with other types of locomotive handicaps to be integrated into the group. For physical education in special schools the pupils whould be arranged into groups according to their ability in order to keep the groups as homogenous and the children's chances as equal as possible. The most important teaching criteria are in this case: the creation of a happy atmosphere, a high degree of clarity, the fulfilment of individual inclinations, the encouragement of independence, the development of community life and the fulfilment of everyday tasks. In swimming, the spina bifida child differs from the normal child in his greater initial fear and in the existence of contractions, a scoliosis, hyperlordosis or -kyphosis due to the resultant instability of the water. Because of this, specifically oriented swim- and work-aids must be used. The didactic procedure is then the same as in the case of normal children. After the child's familiarity with and safety in the water is assured, one can proceed to individual swimming techniques and in a few cases to sport swimming. Bacteriological examination of the water did not yield any results which could cause objection on the grounds of hygiene.", "contents": "[Physical education for spina bifida children in special schools for the physically handicapped (primary school)]. With a rate of 0.5-1/1,000 of the total number of births in West Germany, spina bifida is next to cerebral paresis one of the most frequent congenital defects. Altogether, fifty places in special schools are needed per one million of inhabitants for spina bifida children. The loss of physical unctions is comparable to that in the case of paraplegia. The variety of medical and psychological problems makes the cooperation of highly different branches of study indispensible in a rehabilitation team (neurosurgeon, neuropediatrician, urologist, orthopaedist, pediatrician, educator, social worker, physical therapist). Each team member must be informed about the complete rehabilitation plan. These children's shortage of environmental experience is mainly due to their backwardness as regards motoric development, which cannot be recovered by means of individual physical therapy alone. On the other hand, additional, specifically selected and organised physical education makes possible the necessary mobility and social experiences. By giving the children exercises suitable for their ages it is hoped to achieve a late maturation and stabilization of the personality. In choosing the exercises it is first of all necessary to go back to the so-called fundamental activities like climbing, hanging by one's hands, sliding, pushing oneself up off the ground, swinging or throwing and catching, before going on to wheel-chair sports. Wheel-chair sport promises a varied selection for group exercises (games) and for everyday use. Using the wheel-chair as sports equipment, it is possible for persons with other types of locomotive handicaps to be integrated into the group. For physical education in special schools the pupils whould be arranged into groups according to their ability in order to keep the groups as homogenous and the children's chances as equal as possible. The most important teaching criteria are in this case: the creation of a happy atmosphere, a high degree of clarity, the fulfilment of individual inclinations, the encouragement of independence, the development of community life and the fulfilment of everyday tasks. In swimming, the spina bifida child differs from the normal child in his greater initial fear and in the existence of contractions, a scoliosis, hyperlordosis or -kyphosis due to the resultant instability of the water. Because of this, specifically oriented swim- and work-aids must be used. The didactic procedure is then the same as in the case of normal children. After the child's familiarity with and safety in the water is assured, one can proceed to individual swimming techniques and in a few cases to sport swimming. Bacteriological examination of the water did not yield any results which could cause objection on the grounds of hygiene."} {"id": "PMID:155046", "title": "Impact of chronic illness on child and family: an overview based on five surveys with implications for management.", "content": "For the past eight years the Rochester Child Health Group has systematically investigated chronic illness in childhood with the goal of minimizing the psychosocial sequelae of chronic illness through more optimal management. This overview examines the impact of chronic illness on 404 children and their families in five separate studies: 1) 209 children in a follow-up of all children with chronic symptoms in a previous random sampling of children; 2) 42 children with juvenile arthritis; 3) 44 nephrotic children; 4) 54 asthmatic children; 5) 55 chronically ill children living in rural areas of Western New York. Information was obtained through parental interviews, school reports, and psychological testing of the child. The percentage of parents reporting impact of the child's illness on family differed according to study population. The percentage reporting areas of impact according to severity of the illness is as follows: worry, 75--97; financial, 46--60; fatigue of parent, 31--65; change in sleep arrangements, 17--31; change in furnishings, 15--40; less social life for parents, 12--35; restrictions on travel, 13--40; parental friction, 9--20; sibling neglect, 10--20; sibling resentment, 10--25; embarrassment, 12--20; interference from relatives, 5--17. Over half the parents felt their child's future education, job chances, and social life would be affected. One third reported activity limitations. Compared to a control group of children, a significantly greater percentage of parents of the chronically ill reported teacher concern about their child's effort and behavior, and showed concern about the child having too few friends. Two of the three studies in which psychological appraisals were obtained suggested that more of the ill children than controls showed indices of maladjustment. School information from two studies showed more of the ill children than controls underachieving and being referred to a school psychologist. Work by the Rochester Child Health Group has pointed up several ways in which providers of care can more optimally assist families in order to minimize these problems: 1) identifying families at risk at the onset to find which families may require special support; 2) Assuring that family and all care providers know who is orchestrating care, and that all areas of care are being provided; 3) Assuring that where necessary, an outreach person is meeting the needs of the family and child on an intensive, sustained, caring and creative basis.", "contents": "Impact of chronic illness on child and family: an overview based on five surveys with implications for management. For the past eight years the Rochester Child Health Group has systematically investigated chronic illness in childhood with the goal of minimizing the psychosocial sequelae of chronic illness through more optimal management. This overview examines the impact of chronic illness on 404 children and their families in five separate studies: 1) 209 children in a follow-up of all children with chronic symptoms in a previous random sampling of children; 2) 42 children with juvenile arthritis; 3) 44 nephrotic children; 4) 54 asthmatic children; 5) 55 chronically ill children living in rural areas of Western New York. Information was obtained through parental interviews, school reports, and psychological testing of the child. The percentage of parents reporting impact of the child's illness on family differed according to study population. The percentage reporting areas of impact according to severity of the illness is as follows: worry, 75--97; financial, 46--60; fatigue of parent, 31--65; change in sleep arrangements, 17--31; change in furnishings, 15--40; less social life for parents, 12--35; restrictions on travel, 13--40; parental friction, 9--20; sibling neglect, 10--20; sibling resentment, 10--25; embarrassment, 12--20; interference from relatives, 5--17. Over half the parents felt their child's future education, job chances, and social life would be affected. One third reported activity limitations. Compared to a control group of children, a significantly greater percentage of parents of the chronically ill reported teacher concern about their child's effort and behavior, and showed concern about the child having too few friends. Two of the three studies in which psychological appraisals were obtained suggested that more of the ill children than controls showed indices of maladjustment. School information from two studies showed more of the ill children than controls underachieving and being referred to a school psychologist. Work by the Rochester Child Health Group has pointed up several ways in which providers of care can more optimally assist families in order to minimize these problems: 1) identifying families at risk at the onset to find which families may require special support; 2) Assuring that family and all care providers know who is orchestrating care, and that all areas of care are being provided; 3) Assuring that where necessary, an outreach person is meeting the needs of the family and child on an intensive, sustained, caring and creative basis."} {"id": "PMID:155048", "title": "The influence of calcium on lens ATPase activity.", "content": "The activities of ouabain-sensitive (Na-5-) and ouabain-insensitive ATPases were determined in 3.6 mM calcium-containing and calcium-free media. Three lens tissue segments were studied: the epithelium/capsule segment, the anterior cortical segment and the posterior cortical segment. In the presence of calcium, the Na-K-ATPase activity in each segment was reduced, whereas the ouabain-insensitive ATPase activity in each segment was increased.", "contents": "The influence of calcium on lens ATPase activity. The activities of ouabain-sensitive (Na-5-) and ouabain-insensitive ATPases were determined in 3.6 mM calcium-containing and calcium-free media. Three lens tissue segments were studied: the epithelium/capsule segment, the anterior cortical segment and the posterior cortical segment. In the presence of calcium, the Na-K-ATPase activity in each segment was reduced, whereas the ouabain-insensitive ATPase activity in each segment was increased."} {"id": "PMID:155049", "title": "Chalones and stroma as possible growth-limiting factors in the rat ventral prostate.", "content": "In an attempt to determine the mechanism that limits the growth of the rat ventral prostate, atrophied ventral prostates from orchiectomized inbred rats were implanted into the ventral prostate of other inbred rats. Under the influence of endogenous or exogenous androgen the DNA content of the ventral prostates was increased above normal. This indicates that there is no soluble growth inhibitor diffused in the normal prostate in a concentration sufficient to block cell divisions of the epithelial cells. In other experiments pieces of plastic sponge were implanted into the rat ventral prostate. Orchiectomy and subsequent androgen treatment led to an increased cell number in the prostate. Histologic examination revealed an ingrowth of loose connective tissue and also of normal-looking prostatic tissue in the sponge. The results suggest that implantation of pieces of sponge induced increased growth of the fibromuscular stroma and a secondary proliferation of the epithelial cells. A growth control of the prostatic epithelial cells by the fibromuscular stroma is suggested.", "contents": "Chalones and stroma as possible growth-limiting factors in the rat ventral prostate. In an attempt to determine the mechanism that limits the growth of the rat ventral prostate, atrophied ventral prostates from orchiectomized inbred rats were implanted into the ventral prostate of other inbred rats. Under the influence of endogenous or exogenous androgen the DNA content of the ventral prostates was increased above normal. This indicates that there is no soluble growth inhibitor diffused in the normal prostate in a concentration sufficient to block cell divisions of the epithelial cells. In other experiments pieces of plastic sponge were implanted into the rat ventral prostate. Orchiectomy and subsequent androgen treatment led to an increased cell number in the prostate. Histologic examination revealed an ingrowth of loose connective tissue and also of normal-looking prostatic tissue in the sponge. The results suggest that implantation of pieces of sponge induced increased growth of the fibromuscular stroma and a secondary proliferation of the epithelial cells. A growth control of the prostatic epithelial cells by the fibromuscular stroma is suggested."} {"id": "PMID:155050", "title": "[Comparative study of the effect of Adona on the plasma volume].", "content": "The perfusion of a physiological sodium chloride (Ringer) solution, with the addition of 200 mg/l of Adona, yields a volumetrical effect which lasts for 4 h. After 4 h, the plasma volume shows an average increase of +13%. Perfusions of a physiological NaCl-solution by itself, or of a gelatine solution do not display any volumetrical effect 4 h after the beginning of the perfusion. In the majority of surgical interventions, the surgeon may replace the solution of gelatine and of Dextran which are expansive to store and not devoid of side effects, by a physiological sodium chloride (Ringer) solution to which have been added 2 ampouls of 100 mg/l each (20 ml/l) of Adona.", "contents": "[Comparative study of the effect of Adona on the plasma volume]. The perfusion of a physiological sodium chloride (Ringer) solution, with the addition of 200 mg/l of Adona, yields a volumetrical effect which lasts for 4 h. After 4 h, the plasma volume shows an average increase of +13%. Perfusions of a physiological NaCl-solution by itself, or of a gelatine solution do not display any volumetrical effect 4 h after the beginning of the perfusion. In the majority of surgical interventions, the surgeon may replace the solution of gelatine and of Dextran which are expansive to store and not devoid of side effects, by a physiological sodium chloride (Ringer) solution to which have been added 2 ampouls of 100 mg/l each (20 ml/l) of Adona."} {"id": "PMID:155051", "title": "Benign hereditary (dominant) chorea of early onset.", "content": "Two siblings (one girl 7 1/2 and one boy 6 1/2) are described with a choreic syndrome dating from early childhood without other neurological abnormalities. The father was similarly affected but has markedly improved. Extensive neurological work-up and family history permitted to rule out numerous conditions known to cause abnormal movements in childhood. The clinical entity corresponds to the recently described syndrome of hereditary benign non progressive chorea. To our knowledge it is the first described family with this entity in Switzerland. The relevant literature is reviewed particularly as it pertains to the genetic unity of the syndrome. Its importance lies in its differentiation from the other more severe hereditary abnormal movements of childhood, its non progression and tendency to improve with time. The possible reasons for the only very recent recognition of this purely clinical syndrome are also discussed.", "contents": "Benign hereditary (dominant) chorea of early onset. Two siblings (one girl 7 1/2 and one boy 6 1/2) are described with a choreic syndrome dating from early childhood without other neurological abnormalities. The father was similarly affected but has markedly improved. Extensive neurological work-up and family history permitted to rule out numerous conditions known to cause abnormal movements in childhood. The clinical entity corresponds to the recently described syndrome of hereditary benign non progressive chorea. To our knowledge it is the first described family with this entity in Switzerland. The relevant literature is reviewed particularly as it pertains to the genetic unity of the syndrome. Its importance lies in its differentiation from the other more severe hereditary abnormal movements of childhood, its non progression and tendency to improve with time. The possible reasons for the only very recent recognition of this purely clinical syndrome are also discussed."} {"id": "PMID:155053", "title": "Intraocular lens fixation with dacron.", "content": "To overcome the problem of postoperative lens dislocation, we evaluated a new means of lens fixation. Our experimental studies in rabbits and primates demonstrated that Dacron polyethylene terephtalate induced a cellular reaction from either the anterior or posterior iris surface when placed in contact with the iris, thereby establishing a bond between the Dacron fibers and the iris. Dacron mesh can be attached to the distal portion of either the anterior or posterior loops of a Binkhorst iris clip (4-loop) lens. In the rabbit eye, lens fixation occurred within five days; in the primate eye, 30 days. When combined with silk, Dacron produced tissue ingrowth in the primate eye within 14 days. No unwanted reaction occurred in any animal with the Dacron and silk combination. Being biodegradable, the silk induced faster cellular ingrowth than the Dacron. However, Dacron, which is not biodegradable, provided a permanent means of fixation.", "contents": "Intraocular lens fixation with dacron. To overcome the problem of postoperative lens dislocation, we evaluated a new means of lens fixation. Our experimental studies in rabbits and primates demonstrated that Dacron polyethylene terephtalate induced a cellular reaction from either the anterior or posterior iris surface when placed in contact with the iris, thereby establishing a bond between the Dacron fibers and the iris. Dacron mesh can be attached to the distal portion of either the anterior or posterior loops of a Binkhorst iris clip (4-loop) lens. In the rabbit eye, lens fixation occurred within five days; in the primate eye, 30 days. When combined with silk, Dacron produced tissue ingrowth in the primate eye within 14 days. No unwanted reaction occurred in any animal with the Dacron and silk combination. Being biodegradable, the silk induced faster cellular ingrowth than the Dacron. However, Dacron, which is not biodegradable, provided a permanent means of fixation."} {"id": "PMID:155054", "title": "Depolymerization of brain microtubules by skeletal muscle myosin.", "content": "Brain microtubules are found to disperse rods of skeletal muscle myosin and become decorated with amorphous aggregates of myosin. Then microtubules are partially depolymerized by myosin. Myosin shows high Mg2+-GTPase activity which is not influenced by microtubules, and induces the partial depolymerization of microtubules by exhaustion of GTP in the solution. H-meromyosin depolymerizes microtubules like myosin does. H-meromyosin is, however, contaminated with a trace amount of trypsin, which irreversibly depolymerizes microtubules.", "contents": "Depolymerization of brain microtubules by skeletal muscle myosin. Brain microtubules are found to disperse rods of skeletal muscle myosin and become decorated with amorphous aggregates of myosin. Then microtubules are partially depolymerized by myosin. Myosin shows high Mg2+-GTPase activity which is not influenced by microtubules, and induces the partial depolymerization of microtubules by exhaustion of GTP in the solution. H-meromyosin depolymerizes microtubules like myosin does. H-meromyosin is, however, contaminated with a trace amount of trypsin, which irreversibly depolymerizes microtubules."} {"id": "PMID:155055", "title": "Effects of various concentrations of MgATP on the superprecipitation and ATPase activity of scallop striated muscle myosin B1.", "content": "1. The superprecipitation and ATPase activity of scallop striated muscle myosin B showed essentially the same biphasic pattern as that of vertebrate skeletal muscle myosin B in its responses to changes in the MgATP concentration. Ca2+ had no effect at MgATP concentrations less than 10(-5) M. 2. The superprecipitation of gizzard myosin B showed a weak biphasic pattern, but its ATPase activity showed no sign of a biphasic pattern up to 3 x10(-3) M MgATP, in accord with the result of Bremel (1974). 3. Thus scallop striated muscle is classified into the same group as vertebrate skeletal muscle as far as its response to changes in MgATP concentration is concerned. Gizzard is distinct from the other two kinds of muscle.", "contents": "Effects of various concentrations of MgATP on the superprecipitation and ATPase activity of scallop striated muscle myosin B1. 1. The superprecipitation and ATPase activity of scallop striated muscle myosin B showed essentially the same biphasic pattern as that of vertebrate skeletal muscle myosin B in its responses to changes in the MgATP concentration. Ca2+ had no effect at MgATP concentrations less than 10(-5) M. 2. The superprecipitation of gizzard myosin B showed a weak biphasic pattern, but its ATPase activity showed no sign of a biphasic pattern up to 3 x10(-3) M MgATP, in accord with the result of Bremel (1974). 3. Thus scallop striated muscle is classified into the same group as vertebrate skeletal muscle as far as its response to changes in MgATP concentration is concerned. Gizzard is distinct from the other two kinds of muscle."} {"id": "PMID:155056", "title": "'Freezing' of the calcium-regulated structures of gizzard thin filaments by glutaraldehyde.", "content": "Reconstituted thin filaments (the actin-tropomyosin-leiotonin complex) of chicken gizzard were cross-linked with glutaraldehyde either in the presence or absence of Ca2+. The ability of resultant thin filaments to activate myosin ATPase was 'frozen' in the activated or inactivated state, respectively. This result clearly indicates the existence of actin-linked regulation in smooth muscle.", "contents": "'Freezing' of the calcium-regulated structures of gizzard thin filaments by glutaraldehyde. Reconstituted thin filaments (the actin-tropomyosin-leiotonin complex) of chicken gizzard were cross-linked with glutaraldehyde either in the presence or absence of Ca2+. The ability of resultant thin filaments to activate myosin ATPase was 'frozen' in the activated or inactivated state, respectively. This result clearly indicates the existence of actin-linked regulation in smooth muscle."} {"id": "PMID:155057", "title": "The mechanism of the irreversible inhibition ofrat liver phenylalanine hydroxylase due to treatment with p-chlorophenylalanine. The lack of effect on turnover of phenylalanine hydroxylase.", "content": "The administration of a single dose of p-chlorophenylalanine (360 mg/kg) to rats leads to the irreversible loss of 90% of hepatic phenylalanine hydroxylase activity after 24 h. This loss of activity is not the result of either an alteration in the overall structure of the enzyme, as determined by its antigenicity, or in the total immunologically reactive protein in the liver, as tested with a specific antiserum prepared against native phenylalanine hydroxylase. Neither the rate of synthesis nor the rate of degradation of phenylalanine hydroxylase is changed by p-chlorophenylalanine (pClPhe) treatment. The half-life for the enzyme is about 2 days in control and in pClPhe-treated rats. In addition, there is no detectable incorporation of pClPhe into the phenylalanine hydroxylase molecule itself.", "contents": "The mechanism of the irreversible inhibition ofrat liver phenylalanine hydroxylase due to treatment with p-chlorophenylalanine. The lack of effect on turnover of phenylalanine hydroxylase. The administration of a single dose of p-chlorophenylalanine (360 mg/kg) to rats leads to the irreversible loss of 90% of hepatic phenylalanine hydroxylase activity after 24 h. This loss of activity is not the result of either an alteration in the overall structure of the enzyme, as determined by its antigenicity, or in the total immunologically reactive protein in the liver, as tested with a specific antiserum prepared against native phenylalanine hydroxylase. Neither the rate of synthesis nor the rate of degradation of phenylalanine hydroxylase is changed by p-chlorophenylalanine (pClPhe) treatment. The half-life for the enzyme is about 2 days in control and in pClPhe-treated rats. In addition, there is no detectable incorporation of pClPhe into the phenylalanine hydroxylase molecule itself."} {"id": "PMID:155058", "title": "Purification and reconstitution of the N,N'-dicyclohexylcarbodiimide-sensitive ATPase complex from spinach chloroplasts.", "content": "The dicyclohexylcarbodiimide-sensitive ATPase from spinach chloroplast has been isolated. On sodium dodecyl sulfate gels, seven different polypeptides were seen. Five of these polypeptides coincided with the CF1 subunits, a 7,500-dalton peptide was identified as the proteolipid which interacts with [14C]dicyclohexylcarbodiimide, and there was a 15,500-dalton hydrophobic polypeptide with unknown function. In two-dimentional gels, two additional peptides were resolved, one 17,500 daltons (co-migrating in sodium dodecyl sulfate gels with subunit delta) and one 13,500 daltons (co-migrating with subunit epsilon). Reconstitution was obtained by freezing and thawing the complex with a crude mixture of phospholipids. After reconstitution the complex catalyzed 32P1-ATP exchange (rates of 200 to 400 nmoles x mg-1 x min-1) and ATP formation during acid-to-base transition. These reactions were inhibited by dicyclohexylcarbodiimide and uncouplers. Uncouplers at low concentrations stimulated and at high concentrations inhibited the Mg2+-ATPase activity. ATP hydrolysis and 32P1-ATP exchange were catalyzed by the complex in the presence of either Mg2+ or Mn2+ but not with Ca2+ or Co2+. ATP and GTP were substrates for the exchange reaction but not ADP or CTP.", "contents": "Purification and reconstitution of the N,N'-dicyclohexylcarbodiimide-sensitive ATPase complex from spinach chloroplasts. The dicyclohexylcarbodiimide-sensitive ATPase from spinach chloroplast has been isolated. On sodium dodecyl sulfate gels, seven different polypeptides were seen. Five of these polypeptides coincided with the CF1 subunits, a 7,500-dalton peptide was identified as the proteolipid which interacts with [14C]dicyclohexylcarbodiimide, and there was a 15,500-dalton hydrophobic polypeptide with unknown function. In two-dimentional gels, two additional peptides were resolved, one 17,500 daltons (co-migrating in sodium dodecyl sulfate gels with subunit delta) and one 13,500 daltons (co-migrating with subunit epsilon). Reconstitution was obtained by freezing and thawing the complex with a crude mixture of phospholipids. After reconstitution the complex catalyzed 32P1-ATP exchange (rates of 200 to 400 nmoles x mg-1 x min-1) and ATP formation during acid-to-base transition. These reactions were inhibited by dicyclohexylcarbodiimide and uncouplers. Uncouplers at low concentrations stimulated and at high concentrations inhibited the Mg2+-ATPase activity. ATP hydrolysis and 32P1-ATP exchange were catalyzed by the complex in the presence of either Mg2+ or Mn2+ but not with Ca2+ or Co2+. ATP and GTP were substrates for the exchange reaction but not ADP or CTP."} {"id": "PMID:155059", "title": "The action of trypsin on the gastric (H+ + K+)-ATPase.", "content": "The effect of trypsin on gastric (H+ + K+)-ATPase and K+-phosphatase was studied. Loss of both enzymic activities was biphasic, consisting of a fast and slow phase. Several peptides were produced from the original 105,000-dalton region of the sodium dodecyl sulfate electrophoretic separation, but only two, 87,000 and 47,000 daltons, were labeled following incubation with [gamma-33P]ATP. After a 30-min hydrolysis, 35% of the original peptide remained unaltered and appeared to be a glycoprotein. ATP and ADP abolished the second phase of tryptic inactivation of both activities and only two peptides, of 78,000 and 30,000 daltons, were found on the acrylamide gel in addition to the original 105,000-dalton region, neither of which was labeled by [gamma-33P]ATP. The protection was specific for these nucleotides, AMP, beta, gamma-methylene ATP, TTP, and pNPP being ineffective. Na+ and K+ at high concentrations reduced the rate of loss of activity but no change in the peptides produced was found. The level of phosphoenzyme was increased 2-fold by trypsin treatment, whereas the quantity of K+-sensitive phosphoenzyme remained relatively constant. Thus, the 105,000-dalton region is heterogeneous, consisting of a catalytic subunit (the active site is on a 47,000-dalton fragment), a glycoprotein, and another 105,000-dalton peptide. The action of trypsin is initially to prevent interconversion of a K+-insensitive to a K+-sensitive form of the phosphoenzyme, thus inhibiting hydrolysis.", "contents": "The action of trypsin on the gastric (H+ + K+)-ATPase. The effect of trypsin on gastric (H+ + K+)-ATPase and K+-phosphatase was studied. Loss of both enzymic activities was biphasic, consisting of a fast and slow phase. Several peptides were produced from the original 105,000-dalton region of the sodium dodecyl sulfate electrophoretic separation, but only two, 87,000 and 47,000 daltons, were labeled following incubation with [gamma-33P]ATP. After a 30-min hydrolysis, 35% of the original peptide remained unaltered and appeared to be a glycoprotein. ATP and ADP abolished the second phase of tryptic inactivation of both activities and only two peptides, of 78,000 and 30,000 daltons, were found on the acrylamide gel in addition to the original 105,000-dalton region, neither of which was labeled by [gamma-33P]ATP. The protection was specific for these nucleotides, AMP, beta, gamma-methylene ATP, TTP, and pNPP being ineffective. Na+ and K+ at high concentrations reduced the rate of loss of activity but no change in the peptides produced was found. The level of phosphoenzyme was increased 2-fold by trypsin treatment, whereas the quantity of K+-sensitive phosphoenzyme remained relatively constant. Thus, the 105,000-dalton region is heterogeneous, consisting of a catalytic subunit (the active site is on a 47,000-dalton fragment), a glycoprotein, and another 105,000-dalton peptide. The action of trypsin is initially to prevent interconversion of a K+-insensitive to a K+-sensitive form of the phosphoenzyme, thus inhibiting hydrolysis."} {"id": "PMID:155061", "title": "The use of arylazido-beta-alanyl-ATP as a photoaffinity label for the isolated and membrane-bound mitochondrial ATPase complex.", "content": "The effects of a photoaffinity derivate of ATP, arylazido-beta-alanyl-ATP, 3'-O-(3-[N-(4-azido-2-nitrophenyl)amino]propionyl) adenosine 5'-triphosphate, on submitochondrial particles and the partially purified ATPase complex of beef heart mitochondria have been investigated. In the absence of light the ATP analogue has been found to be a substrate for the E132PA1P1-ATP exchange reaction of submitochondrial particles. When photoirradiated in the presence of arylazido-beta-alanyl-ATP, the ATPase activity and the the the [32P]Pi-ATP exchange reaction are inhibited maximally 80%. Arylazido-beta-alanyl-ATP following photolysis is a noncompetitive inhibitor with respect to ATP while arylazido-beta-alanine, the azido-containing adjunct of the ATP analogue, has no inhibitory effect under the same conditions. The inactivating effect of arylazido-beta-alanyl-ATP is prevented in part by the presence of ATP, or ADP and pyrophosphate. Photolabeling produces a covalent binding of the derivative with the F1ATPase being the major protein labeled. The binding of 0.22 mumol of arylazido-beta-alanyl-ATP/mg of mitochondrial protein is associated with a maximal inhibitory effect. The ATPase activity of the partially purified ATPase complex is also sensitive to photoirradiation in the presence of arylazido-beta-alanyl-ATP. When the ATPase complex is associated with liposomes there is an increase in the specific ATPase activity with a 10-fold increase in Vmax and a 4-fold decrease in KmATP associated with a parallel increase in the apparent affinity and maximal inhibitory effect of the arylazido-beta-alanyl-ATP. The photoinhibition of the ATPase complex in the presence of arylazido-beta-alanyl-ATP results in covalent binding of 1.6 mumol of arylazido-beta-alanyl-ATP/mg of protein. The alpha and beta subunits are the only components of the ATPase complex labeled by the [3H]arylazido-beta-alanyl-ATP. The relationship between the arylazido-beta-alanyl-ATP-labeled sites and the nucleotide binding sites on the mitochondrial ATPase is discussed.", "contents": "The use of arylazido-beta-alanyl-ATP as a photoaffinity label for the isolated and membrane-bound mitochondrial ATPase complex. The effects of a photoaffinity derivate of ATP, arylazido-beta-alanyl-ATP, 3'-O-(3-[N-(4-azido-2-nitrophenyl)amino]propionyl) adenosine 5'-triphosphate, on submitochondrial particles and the partially purified ATPase complex of beef heart mitochondria have been investigated. In the absence of light the ATP analogue has been found to be a substrate for the E132PA1P1-ATP exchange reaction of submitochondrial particles. When photoirradiated in the presence of arylazido-beta-alanyl-ATP, the ATPase activity and the the the [32P]Pi-ATP exchange reaction are inhibited maximally 80%. Arylazido-beta-alanyl-ATP following photolysis is a noncompetitive inhibitor with respect to ATP while arylazido-beta-alanine, the azido-containing adjunct of the ATP analogue, has no inhibitory effect under the same conditions. The inactivating effect of arylazido-beta-alanyl-ATP is prevented in part by the presence of ATP, or ADP and pyrophosphate. Photolabeling produces a covalent binding of the derivative with the F1ATPase being the major protein labeled. The binding of 0.22 mumol of arylazido-beta-alanyl-ATP/mg of mitochondrial protein is associated with a maximal inhibitory effect. The ATPase activity of the partially purified ATPase complex is also sensitive to photoirradiation in the presence of arylazido-beta-alanyl-ATP. When the ATPase complex is associated with liposomes there is an increase in the specific ATPase activity with a 10-fold increase in Vmax and a 4-fold decrease in KmATP associated with a parallel increase in the apparent affinity and maximal inhibitory effect of the arylazido-beta-alanyl-ATP. The photoinhibition of the ATPase complex in the presence of arylazido-beta-alanyl-ATP results in covalent binding of 1.6 mumol of arylazido-beta-alanyl-ATP/mg of protein. The alpha and beta subunits are the only components of the ATPase complex labeled by the [3H]arylazido-beta-alanyl-ATP. The relationship between the arylazido-beta-alanyl-ATP-labeled sites and the nucleotide binding sites on the mitochondrial ATPase is discussed."} {"id": "PMID:155063", "title": "Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. Comparison of the two-two-dimensional electrophoretic patterns of the cyanogen bromide peptides of cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits.", "content": "The CNBr peptides of [14C]carboxymethylated cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits have been compared using a two-dimensional electrophoretic system. The results indicated that there were extensive differences in the peptide \"maps\" of these heavy chains, which included differences in the distribution of radiolabeled thiol peptides. Also, the patterns of heavy chain peptides from the cardiac myosins have been compared with those produced by the heavy chain myosin isozymes from skeletal muscles. Peptide maps of heavy chains from red skeletal muscle myosin closely resembled the pattern of peptides found with cardiac myosin heavy chains from euthyroid rabbits. However, peptide maps of heavy chains from white skeletal muscle myosin were dissimilar to those of the cardiac myosin isozymes. We conclude that thyroxine administration stimulates the synthesis of a cardiac myosin isozyme with a heavy chain primary structure which is different from either of the skeletal muscle myosin isozymes.", "contents": "Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. Comparison of the two-two-dimensional electrophoretic patterns of the cyanogen bromide peptides of cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits. The CNBr peptides of [14C]carboxymethylated cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits have been compared using a two-dimensional electrophoretic system. The results indicated that there were extensive differences in the peptide \"maps\" of these heavy chains, which included differences in the distribution of radiolabeled thiol peptides. Also, the patterns of heavy chain peptides from the cardiac myosins have been compared with those produced by the heavy chain myosin isozymes from skeletal muscles. Peptide maps of heavy chains from red skeletal muscle myosin closely resembled the pattern of peptides found with cardiac myosin heavy chains from euthyroid rabbits. However, peptide maps of heavy chains from white skeletal muscle myosin were dissimilar to those of the cardiac myosin isozymes. We conclude that thyroxine administration stimulates the synthesis of a cardiac myosin isozyme with a heavy chain primary structure which is different from either of the skeletal muscle myosin isozymes."} {"id": "PMID:155064", "title": "The mechanism of the skeletal muscle myosin ATPase. I. Identity of the myosin active sites.", "content": "In the present study, the question of whether the two myosin active sites are identical with respect to ATP binding and hydrolysis was reinvestigated. The stoichiometry of ATP binding to myosin, heavy meromyosin, and subfragment-1 was determined by measuring the fluorescence enhancement caused by the binding of MgATP. The amount of irreversible ATP binding and the magnitude of the initial ATP hydrolysis (initial Pi burst) was determined by measuring [gamma-32P]ATP hydrolysis with and without a cold ATP chase in a three-syringe quenched flow apparatus. The results show that, under a wide variety of experimental conditions: 1) the stoichiometry of ATP binding ranges from 0.8 to 1 mol of ATP/myosin active site for myosin, heavy meromyosin, and subfragment-1, 2) 80 to 100% of this ATP binding is irreversible, 3) 70 to 90% of the irreversibly bound ATP is hydrolyzed in the initial Pi burst, 4) the first order rate constant for the rate-limiting step in ATP hydrolysis by heavy meromyosin is equal to the steady state heavy meromyosin ATPase rate only if the latter is calculated on the basis of two active sites per heavy meromyosin molecule. It is concluded that the two active sites of myosin are identical with respect to ATP binding and hydrolysis.", "contents": "The mechanism of the skeletal muscle myosin ATPase. I. Identity of the myosin active sites. In the present study, the question of whether the two myosin active sites are identical with respect to ATP binding and hydrolysis was reinvestigated. The stoichiometry of ATP binding to myosin, heavy meromyosin, and subfragment-1 was determined by measuring the fluorescence enhancement caused by the binding of MgATP. The amount of irreversible ATP binding and the magnitude of the initial ATP hydrolysis (initial Pi burst) was determined by measuring [gamma-32P]ATP hydrolysis with and without a cold ATP chase in a three-syringe quenched flow apparatus. The results show that, under a wide variety of experimental conditions: 1) the stoichiometry of ATP binding ranges from 0.8 to 1 mol of ATP/myosin active site for myosin, heavy meromyosin, and subfragment-1, 2) 80 to 100% of this ATP binding is irreversible, 3) 70 to 90% of the irreversibly bound ATP is hydrolyzed in the initial Pi burst, 4) the first order rate constant for the rate-limiting step in ATP hydrolysis by heavy meromyosin is equal to the steady state heavy meromyosin ATPase rate only if the latter is calculated on the basis of two active sites per heavy meromyosin molecule. It is concluded that the two active sites of myosin are identical with respect to ATP binding and hydrolysis."} {"id": "PMID:155065", "title": "The mechanism of the skeletal muscle myosin ATPase. II. Relationship between the fluorescence enhancement induced by ATP and the initial Pi burst.", "content": "A major question about the mechanism of the myosin ATPase is how much of the fluorescence change which accompanies the binding of ATP to myosin is due to the conformational change induced by ATP and how much is due to the subsequent hydrolysis of ATP in the initial Pi burst. Several laboratories have suggested that the maximal rate of the fluorescence change represents the rate of the irreversible conformational change induced by ATP. In the present study, the rate of irreversible ATP binding, the rate of the initial Pi burst, and the rate of the fluorescence enhancement were compared under varied conditions. The results show that: 1) the fluorescence enhancement is mainly due to the hydrolysis of ATP in the initial Pi burst rather than to the conformational change induced by the binding of ATP; 2) the rate of the initial Pi burst is considerably slower than the rate of irreversible ATP binding at high ATP concentration; 3) the rate of the initial Pi burst is almost the same as the rate of the fluorescence enhancement. Therefore, the maximum rate of the fluorescence enhancement represents the rate of the initial Pi burst rather than the rate of the conformational change induced by ATP binding.", "contents": "The mechanism of the skeletal muscle myosin ATPase. II. Relationship between the fluorescence enhancement induced by ATP and the initial Pi burst. A major question about the mechanism of the myosin ATPase is how much of the fluorescence change which accompanies the binding of ATP to myosin is due to the conformational change induced by ATP and how much is due to the subsequent hydrolysis of ATP in the initial Pi burst. Several laboratories have suggested that the maximal rate of the fluorescence change represents the rate of the irreversible conformational change induced by ATP. In the present study, the rate of irreversible ATP binding, the rate of the initial Pi burst, and the rate of the fluorescence enhancement were compared under varied conditions. The results show that: 1) the fluorescence enhancement is mainly due to the hydrolysis of ATP in the initial Pi burst rather than to the conformational change induced by the binding of ATP; 2) the rate of the initial Pi burst is considerably slower than the rate of irreversible ATP binding at high ATP concentration; 3) the rate of the initial Pi burst is almost the same as the rate of the fluorescence enhancement. Therefore, the maximum rate of the fluorescence enhancement represents the rate of the initial Pi burst rather than the rate of the conformational change induced by ATP binding."} {"id": "PMID:155066", "title": "Characterization of the plasma membrane Mg2+-ATPase from the yeast, Saccharomyces cerevisiae.", "content": "The plasma membrane of Saccharomyces cerevisiae has a Mg2+-dependent ATPase which is distinct from the mitochondrial Mg2+-ATPase and at the pH optimum of 5.5 has a Km for ATP of 1.7 mM and a Vmax of 0.42 mumol of ATP hydrolyzed/mg/min. At least three protein components of the crude membrane (Mr = 210,000, 160,000 and 115,000) are labeled with [gamma\"32P]ATP at pH 5.5. These phosphoproteins form rapidly in the presence of Mg2+, rapidly turn over the bound phosphate when unlabeled ATP is added, and dephosphorylate after incubation in the presence of hydroxylamine. Vanadate, an inhibitor of the Mg2+-ATPase activity, blocks the phosphorylation of the 210,000- and 115,000-dalton proteins. At pH 7.0, only the 210,000- and 160,000-dalton proteins are phosphorylated. While these three phosphorylated intermediates have not been unambiguously identified as components of the Mg2+-ATPase, the finding of such phosphorylated components in association with that activity implies that this enzyme differs in mechanism from the mitochondrial proton pump and that it is similar in mechanism to the metal ion pumps ((Na+-K+)-ATPase and Ca2+-ATPase) of the mammalian plasma membrane.", "contents": "Characterization of the plasma membrane Mg2+-ATPase from the yeast, Saccharomyces cerevisiae. The plasma membrane of Saccharomyces cerevisiae has a Mg2+-dependent ATPase which is distinct from the mitochondrial Mg2+-ATPase and at the pH optimum of 5.5 has a Km for ATP of 1.7 mM and a Vmax of 0.42 mumol of ATP hydrolyzed/mg/min. At least three protein components of the crude membrane (Mr = 210,000, 160,000 and 115,000) are labeled with [gamma\"32P]ATP at pH 5.5. These phosphoproteins form rapidly in the presence of Mg2+, rapidly turn over the bound phosphate when unlabeled ATP is added, and dephosphorylate after incubation in the presence of hydroxylamine. Vanadate, an inhibitor of the Mg2+-ATPase activity, blocks the phosphorylation of the 210,000- and 115,000-dalton proteins. At pH 7.0, only the 210,000- and 160,000-dalton proteins are phosphorylated. While these three phosphorylated intermediates have not been unambiguously identified as components of the Mg2+-ATPase, the finding of such phosphorylated components in association with that activity implies that this enzyme differs in mechanism from the mitochondrial proton pump and that it is similar in mechanism to the metal ion pumps ((Na+-K+)-ATPase and Ca2+-ATPase) of the mammalian plasma membrane."} {"id": "PMID:155068", "title": "A protein inhibitor of the mitochondrial adenosine triphosphatase complex of rat liver. Purification and characterization.", "content": "A heat-stable protein has been purified from rat liver mitochondria which inhibits the ATP hydrolytic activity of both the soluble and membrane-bound mitochondrial F1-ATPase. The overall purification is about 2400-fold with the major purification step consisting of Sephadex \"affinity\" chromatography. The purified rat liver inhibitor is homogeneous as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 12,300. Amino acid analysis reveals a high content of glutamic acid, lysine, and arginine and the absence of cysteine, proline and methionine. Whether tested with the rat liver or bovine heart ATPase, the liver inhibitor is equally as potent and specific as the heart inhibitor preparation of Pullman and Monroy (Pullman, M.E., and Monroy, G.C. (1963) J. Biol. Chem. 238, 3762-3769). Although the results presented show that the rat liver ATPase inhibitor resembles closely the ATPase inhibitors from other tissues with respect to specific activity and reaction specificity, it is important to note that the rat liver inhibitor is almost 2000 daltons larger than the bovine heart inhibitor, about 5000 daltons larger than ATPase inhibitors of yeast, and contains significantly more lysine residues than both the bovine heart and yeast inhibitors.", "contents": "A protein inhibitor of the mitochondrial adenosine triphosphatase complex of rat liver. Purification and characterization. A heat-stable protein has been purified from rat liver mitochondria which inhibits the ATP hydrolytic activity of both the soluble and membrane-bound mitochondrial F1-ATPase. The overall purification is about 2400-fold with the major purification step consisting of Sephadex \"affinity\" chromatography. The purified rat liver inhibitor is homogeneous as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 12,300. Amino acid analysis reveals a high content of glutamic acid, lysine, and arginine and the absence of cysteine, proline and methionine. Whether tested with the rat liver or bovine heart ATPase, the liver inhibitor is equally as potent and specific as the heart inhibitor preparation of Pullman and Monroy (Pullman, M.E., and Monroy, G.C. (1963) J. Biol. Chem. 238, 3762-3769). Although the results presented show that the rat liver ATPase inhibitor resembles closely the ATPase inhibitors from other tissues with respect to specific activity and reaction specificity, it is important to note that the rat liver inhibitor is almost 2000 daltons larger than the bovine heart inhibitor, about 5000 daltons larger than ATPase inhibitors of yeast, and contains significantly more lysine residues than both the bovine heart and yeast inhibitors."} {"id": "PMID:155070", "title": "Arterio-venous shunt with percutaneous leads in calves for long-term in vivo testing of blood-contact materials.", "content": "In six calves an extracorporeal arteriovenous shunt in combination with a successful type of percutaneous lead has been implanted. Flow chambers with various test materials can be inserted. Preliminary results show that this shunt can be used for long term tests for evaluation of blood contact material and studies about thrombus formation in an ex vivo setting as well as for permanent blood access for the purpose of various measurements, drug application and for hemodialysis.", "contents": "Arterio-venous shunt with percutaneous leads in calves for long-term in vivo testing of blood-contact materials. In six calves an extracorporeal arteriovenous shunt in combination with a successful type of percutaneous lead has been implanted. Flow chambers with various test materials can be inserted. Preliminary results show that this shunt can be used for long term tests for evaluation of blood contact material and studies about thrombus formation in an ex vivo setting as well as for permanent blood access for the purpose of various measurements, drug application and for hemodialysis."} {"id": "PMID:155072", "title": "[Unusual procedures in the cure of aneurisms of the subrenal aorta (author's transl)].", "content": "From 1959 to 1977, out of 419 aneurisms of the subrenal aorta operated on, 84 were by unusual procedures: --25 restoratory endo-aneurismorraphies with thrombo-endarterectomy were carried out for small aneurisms in young subjects; --4 were enveloped in dacron (in particular for a risk of distal acute post-operative thrombosis); --in 55 cases, these were high risk surgical subjects where conventional treatment by removal of the aneurism and graft appeared to have a bad prognosis: 43 were treated by axillo-femoral by pass with ligature of the aorta just above the aneurism either for acute arterial obstruction with sensory and motor ischemia, or for embolism or for subjacent obstruction; 12 large advanced aneurisms with fissures of tears were treated by axillo-bifemoral by pass and exclusion. Depending on the results obtained, are deduced the operative indications for these procedures.", "contents": "[Unusual procedures in the cure of aneurisms of the subrenal aorta (author's transl)]. From 1959 to 1977, out of 419 aneurisms of the subrenal aorta operated on, 84 were by unusual procedures: --25 restoratory endo-aneurismorraphies with thrombo-endarterectomy were carried out for small aneurisms in young subjects; --4 were enveloped in dacron (in particular for a risk of distal acute post-operative thrombosis); --in 55 cases, these were high risk surgical subjects where conventional treatment by removal of the aneurism and graft appeared to have a bad prognosis: 43 were treated by axillo-femoral by pass with ligature of the aorta just above the aneurism either for acute arterial obstruction with sensory and motor ischemia, or for embolism or for subjacent obstruction; 12 large advanced aneurisms with fissures of tears were treated by axillo-bifemoral by pass and exclusion. Depending on the results obtained, are deduced the operative indications for these procedures."} {"id": "PMID:155073", "title": "[Treatment of post-operative ventral hernia: elementary biomechanical basis. Report of 51 cases treated by mersilene mesh (author's transl)].", "content": "Elementary functional anatomy of the normal abdominal wall and following incisional hernia are described. The treatment of postoperative hernia should be based on this: its object is to restore the morphology and functions of the abdominal wall, in particular its respiratory function. It may be necessary to carry out gradual pneumo-peritoneum before parietal repair. A mersilene mesh was used by the authors in 51 cases. Certain rules should be observed when this prosthesis is placed in position so that the abdominal muscles find the conditions closest to their normal function.", "contents": "[Treatment of post-operative ventral hernia: elementary biomechanical basis. Report of 51 cases treated by mersilene mesh (author's transl)]. Elementary functional anatomy of the normal abdominal wall and following incisional hernia are described. The treatment of postoperative hernia should be based on this: its object is to restore the morphology and functions of the abdominal wall, in particular its respiratory function. It may be necessary to carry out gradual pneumo-peritoneum before parietal repair. A mersilene mesh was used by the authors in 51 cases. Certain rules should be observed when this prosthesis is placed in position so that the abdominal muscles find the conditions closest to their normal function."} {"id": "PMID:155074", "title": "Endocrine features of an adrenal-like tumor of the ovary.", "content": "Detailed in vivo endocrine studies of a virilizing adrenal-like tumor of the ovary are reported. A nonspecific steroidogenic baseline profile was observed in the face of clearcut histological adrenal-like features. Dynamic testing disclosed incomplete dexamethasone-related steroidogenic suppression suggestive of partial tumoral autonomy. At the same time, the observation of sizable dexamethasone-related steroidogenic decrements, unaccounted for by normal adrenal contribution, may be interpreted to suggest a direct, pharmacological, inhibitory effect of dexamethasone on tumoral and/or ovarian stromal steroidogenesis. These observations confirm the limited role of baseline steroid profiling and dynamic testing in the preoperative localization of androgen-secreting tumors. Reversible dysfunction of hypothalamic gonadotropic feedback mechanisms was suggested by combined single dose LRH-clomiphene testing. Complete resolution followed tumor removal.", "contents": "Endocrine features of an adrenal-like tumor of the ovary. Detailed in vivo endocrine studies of a virilizing adrenal-like tumor of the ovary are reported. A nonspecific steroidogenic baseline profile was observed in the face of clearcut histological adrenal-like features. Dynamic testing disclosed incomplete dexamethasone-related steroidogenic suppression suggestive of partial tumoral autonomy. At the same time, the observation of sizable dexamethasone-related steroidogenic decrements, unaccounted for by normal adrenal contribution, may be interpreted to suggest a direct, pharmacological, inhibitory effect of dexamethasone on tumoral and/or ovarian stromal steroidogenesis. These observations confirm the limited role of baseline steroid profiling and dynamic testing in the preoperative localization of androgen-secreting tumors. Reversible dysfunction of hypothalamic gonadotropic feedback mechanisms was suggested by combined single dose LRH-clomiphene testing. Complete resolution followed tumor removal."} {"id": "PMID:155075", "title": "Mechanism of the hypocalcemic effect of mithramycin.", "content": "Mithramycin is effective in the treatment of hypercalcemia. The mechanism of its hypocalcemic effect was studied in six patients with hypercalcemia by serum 85Sr or 45Ca kinetic techniques. Mithramycin was given at two dosage levels (25 or 50 microgram/kg iv). Mithramycin at the low dosage had little effect on the rate of bone accretion. However, at both dosage levels, mithramycin caused an upward shift of the slope of the specific activity curve, indicating an inhibitory effect on bone resorption. This effect started 6-12 h after a 25-microgram/kg dose of mithramycin and lasted from 4-6 days. It appears that mithramycin has a preferential effect on bone resorption.", "contents": "Mechanism of the hypocalcemic effect of mithramycin. Mithramycin is effective in the treatment of hypercalcemia. The mechanism of its hypocalcemic effect was studied in six patients with hypercalcemia by serum 85Sr or 45Ca kinetic techniques. Mithramycin was given at two dosage levels (25 or 50 microgram/kg iv). Mithramycin at the low dosage had little effect on the rate of bone accretion. However, at both dosage levels, mithramycin caused an upward shift of the slope of the specific activity curve, indicating an inhibitory effect on bone resorption. This effect started 6-12 h after a 25-microgram/kg dose of mithramycin and lasted from 4-6 days. It appears that mithramycin has a preferential effect on bone resorption."} {"id": "PMID:155076", "title": "Changes in lymphocyte activity after thermal injury. The role of suppressor cells.", "content": "The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients.", "contents": "Changes in lymphocyte activity after thermal injury. The role of suppressor cells. The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients."} {"id": "PMID:155077", "title": "Human C4-binding protein. Association with immune complexes in vitro and in vivo.", "content": "C4-binding protein (bp), a glycoprotein with specific binding affinity for the activated form of C4 (C4b), has recently been isolated from human serum and partially characterized. This report demonstrates that C4-bp is incorporated into soluble immune complexes after complement activation in vitro. The reaction requires Ca++ ions and the presence of C4 in serum. Immunopathological studies of various forms of glomerulonephritis revealed intense C4-bp deposition in glomeruli from patients with immune-complex type of pathogenesis. C4-bp deposition was in close correlation with that of C4. These observations, together with the in vitro association of C4-bp to immune complexes, support the notion that the deposits in glomeruli represent the local accumulation of immune complexes.", "contents": "Human C4-binding protein. Association with immune complexes in vitro and in vivo. C4-binding protein (bp), a glycoprotein with specific binding affinity for the activated form of C4 (C4b), has recently been isolated from human serum and partially characterized. This report demonstrates that C4-bp is incorporated into soluble immune complexes after complement activation in vitro. The reaction requires Ca++ ions and the presence of C4 in serum. Immunopathological studies of various forms of glomerulonephritis revealed intense C4-bp deposition in glomeruli from patients with immune-complex type of pathogenesis. C4-bp deposition was in close correlation with that of C4. These observations, together with the in vitro association of C4-bp to immune complexes, support the notion that the deposits in glomeruli represent the local accumulation of immune complexes."} {"id": "PMID:155078", "title": "Trend analysis of jaw jerk action potential-amplitude data.", "content": "The amplitude of the jaw jerk action potential (MSP) is a parameter with potential diagnostic value. It has apparently a large and irregular variation which has not yet been subjected to a thorough analysis. It is important to know if samples of MSP contain trends. The occurrence of trends indicates that the average value is influenced in a principally different way by changes in the number of observations per sample than if trends do not occur. If, for instance, there is a positive linear trend in the data, this means that the average value is larger if the number of observations is small. Samples of MSPs therefore were recorded, using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly subjects, and subjected to trend analysis. Trends of the 1--4th grade occurred in 51% of the samples. Both positive and negative linear trends were found and had about the same frequency. The trend components were, however, randomly distributed. Comparisons between groups may therefore be made without the claim of trend-free samples. This significantly facilitates the use of the parameter MSP-amplitude, since it is difficult to obtain samples which have a normal and identical distribution.", "contents": "Trend analysis of jaw jerk action potential-amplitude data. The amplitude of the jaw jerk action potential (MSP) is a parameter with potential diagnostic value. It has apparently a large and irregular variation which has not yet been subjected to a thorough analysis. It is important to know if samples of MSP contain trends. The occurrence of trends indicates that the average value is influenced in a principally different way by changes in the number of observations per sample than if trends do not occur. If, for instance, there is a positive linear trend in the data, this means that the average value is larger if the number of observations is small. Samples of MSPs therefore were recorded, using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly subjects, and subjected to trend analysis. Trends of the 1--4th grade occurred in 51% of the samples. Both positive and negative linear trends were found and had about the same frequency. The trend components were, however, randomly distributed. Comparisons between groups may therefore be made without the claim of trend-free samples. This significantly facilitates the use of the parameter MSP-amplitude, since it is difficult to obtain samples which have a normal and identical distribution."} {"id": "PMID:155079", "title": "Standard values of the amplitude of jaw jerk action potential and differences due to age, sex and L-dopa treatment.", "content": "The amplitude of the jaw jerk action potential (MSP) is a parameter with possible diagnostic value. Standard values have, however, not yet been established. MSPs were recorded using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly healthy males and females. The group means ranged from 0.26 to 2.11 mV in the masseter and from 0.17 to 0.81 mV in the anterior temporalis. The amplitude of MSP was higher in females than in males, decreased in elderly subjects and lower in the temporalis than in the masseter. The jaw jerk action potentials also were recorded in four subjects before and after L-Dopa administration. The amplitude increased by about 90%. It is concluded that the parameter MSP amplitude can be useful in the studies of muscle spindle sensitivity and the influence of various physiological, pathophysiological and pharmacological factors on the nervous regulation and muscle function in the masticatory system.", "contents": "Standard values of the amplitude of jaw jerk action potential and differences due to age, sex and L-dopa treatment. The amplitude of the jaw jerk action potential (MSP) is a parameter with possible diagnostic value. Standard values have, however, not yet been established. MSPs were recorded using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly healthy males and females. The group means ranged from 0.26 to 2.11 mV in the masseter and from 0.17 to 0.81 mV in the anterior temporalis. The amplitude of MSP was higher in females than in males, decreased in elderly subjects and lower in the temporalis than in the masseter. The jaw jerk action potentials also were recorded in four subjects before and after L-Dopa administration. The amplitude increased by about 90%. It is concluded that the parameter MSP amplitude can be useful in the studies of muscle spindle sensitivity and the influence of various physiological, pathophysiological and pharmacological factors on the nervous regulation and muscle function in the masticatory system."} {"id": "PMID:155082", "title": "Reasonable expectations in geriatric rehabilitation.", "content": "Rehabilitation and traditional medical treatment have different primary orientations within philosophic, operational and time frameworks. As a result, traditionally trained physicians often do not understand the possible benefits of energetic rehabilitation efforts in the elderly. Accurate assessment includes differentiating the irreversible handicaps of normal aging from the disabilities of remediable disease. Such assessment is the essential prerequisite of effective rehabilitation; together with positive attitudes and continuous reevaluation, the likelihood of a successful outcome is greatly enhanced.", "contents": "Reasonable expectations in geriatric rehabilitation. Rehabilitation and traditional medical treatment have different primary orientations within philosophic, operational and time frameworks. As a result, traditionally trained physicians often do not understand the possible benefits of energetic rehabilitation efforts in the elderly. Accurate assessment includes differentiating the irreversible handicaps of normal aging from the disabilities of remediable disease. Such assessment is the essential prerequisite of effective rehabilitation; together with positive attitudes and continuous reevaluation, the likelihood of a successful outcome is greatly enhanced."} {"id": "PMID:155083", "title": "[The effects of intraocular irrigating solutions on the human corneal endothelium (author's transl)].", "content": "Human corneas from enucleated eyes get thicker during perfusion with B.S.S. On the contrary, their thickness decreases when perfused with T.C. Earle solution. Addition of reduced glutathion and adenosine does not change the results obtained with T.C. Earle. Histological study of the endothelium after a 24 hours perfusion demonstrates a better conservation of the cells with T.C. Earle and T.C. Earle glutathion--adenosine than with B.S.S.", "contents": "[The effects of intraocular irrigating solutions on the human corneal endothelium (author's transl)]. Human corneas from enucleated eyes get thicker during perfusion with B.S.S. On the contrary, their thickness decreases when perfused with T.C. Earle solution. Addition of reduced glutathion and adenosine does not change the results obtained with T.C. Earle. Histological study of the endothelium after a 24 hours perfusion demonstrates a better conservation of the cells with T.C. Earle and T.C. Earle glutathion--adenosine than with B.S.S."} {"id": "PMID:155084", "title": "[Drainage of subretinal fluid: technic and results].", "content": "The drainage of subretinal fluid (S.R.F.) after choroidal diathermy offers a distinct advantage: important reduction of massive haemorrhages from the drainage site (4% vs 48% in the non diathermy group in our series). According to us it is not a decisive factor for the anatomical prognosis because complications of drainage in themselves seem to be a quite infrequent cause of anatomical failure. On the other hand we think that visual outcome is better in the diathermy group because of a diminution of macular haemorrhages.", "contents": "[Drainage of subretinal fluid: technic and results]. The drainage of subretinal fluid (S.R.F.) after choroidal diathermy offers a distinct advantage: important reduction of massive haemorrhages from the drainage site (4% vs 48% in the non diathermy group in our series). According to us it is not a decisive factor for the anatomical prognosis because complications of drainage in themselves seem to be a quite infrequent cause of anatomical failure. On the other hand we think that visual outcome is better in the diathermy group because of a diminution of macular haemorrhages."} {"id": "PMID:155085", "title": "[Massive bilateral orbito-palpebral hematoma complicating acute myeloblastic leukemia].", "content": "The authors present a case of acute mieloblastic leucemia, having as an unique symptom a massive bilateral orbito-palpebral hematoma, but having not other symptoms of the hemoragipar syndroms common in acute leucemiae. After a short period of retreat of the disease, the goeson, leading to death.", "contents": "[Massive bilateral orbito-palpebral hematoma complicating acute myeloblastic leukemia]. The authors present a case of acute mieloblastic leucemia, having as an unique symptom a massive bilateral orbito-palpebral hematoma, but having not other symptoms of the hemoragipar syndroms common in acute leucemiae. After a short period of retreat of the disease, the goeson, leading to death."} {"id": "PMID:155086", "title": "[A new lacrimal intubation set (author's transl)].", "content": "The authors report a new lacrimal intubation set made with two very malleable metal probes and with a silicone tube. The system can be used during the repair of the nasolacrimal duct injuries, during dacryorhinocystostomy, and also for the repair of canaliculus injuries with the little set.", "contents": "[A new lacrimal intubation set (author's transl)]. The authors report a new lacrimal intubation set made with two very malleable metal probes and with a silicone tube. The system can be used during the repair of the nasolacrimal duct injuries, during dacryorhinocystostomy, and also for the repair of canaliculus injuries with the little set."} {"id": "PMID:155087", "title": "[A criticism of Lancaster's test and its variations (its inadequacies during the study of oculomotor paralyses) (author's transl)].", "content": "Lancaster's test has many technical inconveniences : Its interpretation is sometimes difficult or impossible. The information it gives is often incomplete. It is of no value in cases with binocular motor lesions. It should always be combined with other oculomotor examinations.", "contents": "[A criticism of Lancaster's test and its variations (its inadequacies during the study of oculomotor paralyses) (author's transl)]. Lancaster's test has many technical inconveniences : Its interpretation is sometimes difficult or impossible. The information it gives is often incomplete. It is of no value in cases with binocular motor lesions. It should always be combined with other oculomotor examinations."} {"id": "PMID:155088", "title": "[Is the Fadenoperation easy or difficult? (author's transl)].", "content": "The operative indications are more or less difficult according to the clinical type ; some of them belong to a very high specialization. The operative technique is not very difficult if the operator is accustomed with the surgery of the posterior segment. On the contrary, the operator who is only accustomed with the surgery of the anterior segment or the classical techniques for strabismus, will find real difficulties.", "contents": "[Is the Fadenoperation easy or difficult? (author's transl)]. The operative indications are more or less difficult according to the clinical type ; some of them belong to a very high specialization. The operative technique is not very difficult if the operator is accustomed with the surgery of the posterior segment. On the contrary, the operator who is only accustomed with the surgery of the anterior segment or the classical techniques for strabismus, will find real difficulties."} {"id": "PMID:155095", "title": "[Experimental studies with timolol: a new ocular hypotensive agent (author's transl)].", "content": "The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented.", "contents": "[Experimental studies with timolol: a new ocular hypotensive agent (author's transl)]. The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented."} {"id": "PMID:155096", "title": "[A new beta-blocking agent in the treatment of chronic open-angle glaucoma: timolol maleate. Effect of instillation of 1 drop on the intraocular pressure].", "content": "A total of 45 patients with chronic open-angle glaucoma were divided randomly into three groups of fifteen. Each patient in each group was given one drop into one eye (the other eye serving as a control), of either placebo, timolol 0,5%, or timolol 1,5%. The patients were observed for a period of seven hours, and results showed that timolol was effective in reducing ocular tension when compared to placebo. It was also rapid in action (one to two hours after instillation), and no side-effects were noted. Timolol 0,5% appears to be as equally effective as the 1,5% strength.", "contents": "[A new beta-blocking agent in the treatment of chronic open-angle glaucoma: timolol maleate. Effect of instillation of 1 drop on the intraocular pressure]. A total of 45 patients with chronic open-angle glaucoma were divided randomly into three groups of fifteen. Each patient in each group was given one drop into one eye (the other eye serving as a control), of either placebo, timolol 0,5%, or timolol 1,5%. The patients were observed for a period of seven hours, and results showed that timolol was effective in reducing ocular tension when compared to placebo. It was also rapid in action (one to two hours after instillation), and no side-effects were noted. Timolol 0,5% appears to be as equally effective as the 1,5% strength."} {"id": "PMID:155097", "title": "[Results of a double-blind medium-term study comparing effects of timolol maleate and epinephrine in 120 patients with chronic open-angle glaucoma].", "content": "A double-blind medium term study of the activity of timolol in chronic open-angle glaucoma was conducted in four French ophthalmological centers, using the same protocol. A total of 119 patients were treated: --60 with timolol; --59 with \u00e9pin\u00e9phrine, for comparison. Results showed a significantly superior efficacy for timolol over \u00e9pin\u00e9phrine, after in weeks of treatment. Good tonometric control was obtained in 81.6% of the patients treated with timolol, against 52.5% of those receiving \u00e9pin\u00e9phrine. In 68% of the glaucomatons patients treated with timolol, good tonometric control was obtained with the lowest dose preparation containing 0.1%. No side-effects were noted during the study, either locally or generally (particularly blood pressure changes).", "contents": "[Results of a double-blind medium-term study comparing effects of timolol maleate and epinephrine in 120 patients with chronic open-angle glaucoma]. A double-blind medium term study of the activity of timolol in chronic open-angle glaucoma was conducted in four French ophthalmological centers, using the same protocol. A total of 119 patients were treated: --60 with timolol; --59 with \u00e9pin\u00e9phrine, for comparison. Results showed a significantly superior efficacy for timolol over \u00e9pin\u00e9phrine, after in weeks of treatment. Good tonometric control was obtained in 81.6% of the patients treated with timolol, against 52.5% of those receiving \u00e9pin\u00e9phrine. In 68% of the glaucomatons patients treated with timolol, good tonometric control was obtained with the lowest dose preparation containing 0.1%. No side-effects were noted during the study, either locally or generally (particularly blood pressure changes)."} {"id": "PMID:155098", "title": "[Results of a double-blind study comparing the effects of timolol and pilocarpine in 110 patients with chronic open-angle glaucoma].", "content": "Following a seventeen weeks study including 110 patients with open-angle glaucoma, 81,8% of the patients treated by timolol, administered twice a day, had a satisfactory control of their intraocular pressure, against only 41,8% of those patients treated by pilocarpine, administered four times a day. The side effects liable to timolol are clinically reduced, in a osit with pilocarpine which is followed by a series of well-known subjective and objective signs often causing discomfort to the patients.", "contents": "[Results of a double-blind study comparing the effects of timolol and pilocarpine in 110 patients with chronic open-angle glaucoma]. Following a seventeen weeks study including 110 patients with open-angle glaucoma, 81,8% of the patients treated by timolol, administered twice a day, had a satisfactory control of their intraocular pressure, against only 41,8% of those patients treated by pilocarpine, administered four times a day. The side effects liable to timolol are clinically reduced, in a osit with pilocarpine which is followed by a series of well-known subjective and objective signs often causing discomfort to the patients."} {"id": "PMID:155099", "title": "[Effect of daily instillations of timolol on the nycthemeral tension in subjects with chronic open-angle glaucoma (author's transl)].", "content": "This study included 22 patients with chronic open-angle glaucoma who were treated with either 0.25% or 0.5% timolol. The results showed that a single daily instillation of 0.25% or 0.5% timolol was effective, without producing any side-effects. It was interesting to note that timolol caused the tension peaks to disappear, the nycthemeral graph curve becoming plateau-shaped.", "contents": "[Effect of daily instillations of timolol on the nycthemeral tension in subjects with chronic open-angle glaucoma (author's transl)]. This study included 22 patients with chronic open-angle glaucoma who were treated with either 0.25% or 0.5% timolol. The results showed that a single daily instillation of 0.25% or 0.5% timolol was effective, without producing any side-effects. It was interesting to note that timolol caused the tension peaks to disappear, the nycthemeral graph curve becoming plateau-shaped."} {"id": "PMID:155100", "title": "[Timolol maleate: results of its long-term action in the treatment of chronic primary open-angle glaucoma].", "content": "Three groups of patients with chronic open-angle glaucoma, who had ineluded in the previous study, had been treated with timolol twice daily for more than a year. The long-term results confirm the efficacity noted in the medium-term survey, and the absence of side-effects, especially those related to the pulse rate and blood pressure in some of the patients. Drug associations had been necessary:--pilocarpin,--acetazolamid, seem to have the best synergic action with timolol.", "contents": "[Timolol maleate: results of its long-term action in the treatment of chronic primary open-angle glaucoma]. Three groups of patients with chronic open-angle glaucoma, who had ineluded in the previous study, had been treated with timolol twice daily for more than a year. The long-term results confirm the efficacity noted in the medium-term survey, and the absence of side-effects, especially those related to the pulse rate and blood pressure in some of the patients. Drug associations had been necessary:--pilocarpin,--acetazolamid, seem to have the best synergic action with timolol."} {"id": "PMID:155101", "title": "[A single dose of maleate of timolol given orally: the effect on the ocular pressure (author's transl)].", "content": "A single dose of 5 mg of maleate of timolol given orally to glaucomatous patients, considerably lowers their I.O.P. during a period of time of at least 6 hours. It causes only a slight decrease in blood pressure and pulse rate.", "contents": "[A single dose of maleate of timolol given orally: the effect on the ocular pressure (author's transl)]. A single dose of 5 mg of maleate of timolol given orally to glaucomatous patients, considerably lowers their I.O.P. during a period of time of at least 6 hours. It causes only a slight decrease in blood pressure and pulse rate."} {"id": "PMID:155106", "title": "[Hypoplasia of the optic nerve head].", "content": "Optic nerve hypoplasia is not a rare eventuality in children. This report discusses the clinical features of 10 new cases on a multiple point of view including optic canal tomography, fluorescein angiography and cat's examination. Optic nerve hypoplasia is not always accompanied by decreased visual acuity: sector fields are often identified in these cases.", "contents": "[Hypoplasia of the optic nerve head]. Optic nerve hypoplasia is not a rare eventuality in children. This report discusses the clinical features of 10 new cases on a multiple point of view including optic canal tomography, fluorescein angiography and cat's examination. Optic nerve hypoplasia is not always accompanied by decreased visual acuity: sector fields are often identified in these cases."} {"id": "PMID:155107", "title": "[Primary malignant melanoma of the cornea (author's transl)].", "content": "In this communication, we present a case of malignant melanoma of the cornea, in an 80-year old female. The tumor, covering 3/4 of the cornea, had a lobulated appearance, pinkish colour with vascularization and pigment granules, in a few places. The limbal area was free of tumor. Histologic examination indicated that the melanoma was primary, of the epithelioid type, with a few areas of spindle type cells.", "contents": "[Primary malignant melanoma of the cornea (author's transl)]. In this communication, we present a case of malignant melanoma of the cornea, in an 80-year old female. The tumor, covering 3/4 of the cornea, had a lobulated appearance, pinkish colour with vascularization and pigment granules, in a few places. The limbal area was free of tumor. Histologic examination indicated that the melanoma was primary, of the epithelioid type, with a few areas of spindle type cells."} {"id": "PMID:155108", "title": "[Menkes' disease: apropos of a recent case].", "content": "The authors describes a case of Menkes' disease, sex-linked recessive hereditary disease characterized by early progressive psychomotor deterioration, failure to gain weight, seizures, hypothermie and characteristic Kinky hair (Pilitorti). This boy is a blind child, unable to fix and follow light. Fundus examination shows optic nerve atrophy with tortuosity of the retinal blood vessels. The case is discussed in the light of similar and others reports in the literature. The disease is believed to be cause by a generalized copper deficiency in the body by defect in copper intestinal absorbtion. The pathologic changes in the retina are similar to those seen in the brain which shows diffuse neuronal degeneration lose of nerve filers and optic atrophy. Retinal changes should be reversible by short term systemic copper administration.", "contents": "[Menkes' disease: apropos of a recent case]. The authors describes a case of Menkes' disease, sex-linked recessive hereditary disease characterized by early progressive psychomotor deterioration, failure to gain weight, seizures, hypothermie and characteristic Kinky hair (Pilitorti). This boy is a blind child, unable to fix and follow light. Fundus examination shows optic nerve atrophy with tortuosity of the retinal blood vessels. The case is discussed in the light of similar and others reports in the literature. The disease is believed to be cause by a generalized copper deficiency in the body by defect in copper intestinal absorbtion. The pathologic changes in the retina are similar to those seen in the brain which shows diffuse neuronal degeneration lose of nerve filers and optic atrophy. Retinal changes should be reversible by short term systemic copper administration."} {"id": "PMID:155109", "title": "[Fluorescence angiography: personal technics of automatized development of films and printing].", "content": "The film of an angiography by fluorescence presents specific particular characteristics. Treatment of the film has to be adapted to these particularities, and the chemical products used have to be specially chosen. In this way, the results obtained can be greatly improved. The procedure can be automatized by the use of a simple apparatus, and printing on paper causes no particular difficulty.", "contents": "[Fluorescence angiography: personal technics of automatized development of films and printing]. The film of an angiography by fluorescence presents specific particular characteristics. Treatment of the film has to be adapted to these particularities, and the chemical products used have to be specially chosen. In this way, the results obtained can be greatly improved. The procedure can be automatized by the use of a simple apparatus, and printing on paper causes no particular difficulty."} {"id": "PMID:155110", "title": "[A case of cavernous hemangioma of the retina].", "content": "A case of hemangioma of the retina is reported. Its typical ophtalmoscopic and fluorescein angiographic aspects are studied. The benign evolution is stressed in spite of a possible macular risk checked by argon laser therapy.", "contents": "[A case of cavernous hemangioma of the retina]. A case of hemangioma of the retina is reported. Its typical ophtalmoscopic and fluorescein angiographic aspects are studied. The benign evolution is stressed in spite of a possible macular risk checked by argon laser therapy."} {"id": "PMID:155111", "title": "[Painful ophthalmoplegia and cavernous sinus syndrome of inflammatory origin (discussion of 2 cases)].", "content": "Two patients with unilateral painful ophthalmoplegia are presented, a woman of 26 and a man of 28. In both cases the phlebography of the orbit shows an alteration of the orbital veinous blood flow, specially of the third segment of the superior orbital vein. Another characteristic feature of this syndrom is efficiency of corticotherapy and heparinotherapy, which may suggest an inflammatory and thrombophlebitic origin.", "contents": "[Painful ophthalmoplegia and cavernous sinus syndrome of inflammatory origin (discussion of 2 cases)]. Two patients with unilateral painful ophthalmoplegia are presented, a woman of 26 and a man of 28. In both cases the phlebography of the orbit shows an alteration of the orbital veinous blood flow, specially of the third segment of the superior orbital vein. Another characteristic feature of this syndrom is efficiency of corticotherapy and heparinotherapy, which may suggest an inflammatory and thrombophlebitic origin."} {"id": "PMID:155112", "title": "[Surgical management of divergent strabismus (author's transl)].", "content": "This study, about 111 cases of exodeviations, establishes a guideline for surgical management of divergent strabismus. First the main points of the clinical examination, and the different classifications of the exodeviations are exposed. Then the technics of surgical treatment are defined, with or without pre or post surgical orthoptic treatment. The conclusions are as following: -- some clinical elements guide our treatment: the refraction, the age at onset, the study of the deviation after constant use of prisms, the existence of A or V syndrome. -- The main points of the surgical management are: the age of surgery, the choice of technic (symmetrical or not), the usefulness of a transient overcorrection, and above all the quantative rules for the surgical treatment. So it as been possible to stress the functional result is quite depending on the clinical type of exodeviation.", "contents": "[Surgical management of divergent strabismus (author's transl)]. This study, about 111 cases of exodeviations, establishes a guideline for surgical management of divergent strabismus. First the main points of the clinical examination, and the different classifications of the exodeviations are exposed. Then the technics of surgical treatment are defined, with or without pre or post surgical orthoptic treatment. The conclusions are as following: -- some clinical elements guide our treatment: the refraction, the age at onset, the study of the deviation after constant use of prisms, the existence of A or V syndrome. -- The main points of the surgical management are: the age of surgery, the choice of technic (symmetrical or not), the usefulness of a transient overcorrection, and above all the quantative rules for the surgical treatment. So it as been possible to stress the functional result is quite depending on the clinical type of exodeviation."} {"id": "PMID:155115", "title": "[Future of coelioscopy tappings of ovarien cysts (author's transl)].", "content": "In a study of 136 tapping of ovarien cysts carried out in the surgical departement of Broca Hospital from 1968 to 1971, the authors point out the diagnostic interest of such a practice, which is harmeless if the contra-indications are respected and often easily carried out (tapping needle by Mintz). The macroscopic and cytological aspect of the liquid tapped enable one to make a precise diagnostic in almost all cases and to lead the therapy in the proper direction.", "contents": "[Future of coelioscopy tappings of ovarien cysts (author's transl)]. In a study of 136 tapping of ovarien cysts carried out in the surgical departement of Broca Hospital from 1968 to 1971, the authors point out the diagnostic interest of such a practice, which is harmeless if the contra-indications are respected and often easily carried out (tapping needle by Mintz). The macroscopic and cytological aspect of the liquid tapped enable one to make a precise diagnostic in almost all cases and to lead the therapy in the proper direction."} {"id": "PMID:155116", "title": "[Meadows syndrome. A case history (author's transl)].", "content": "The authors, having studied a case of Meadows syndrome, confirm that this cardiomyopathy is a specific entity in pregnancy and the puerperium. They point out the difficulties in diagnosis, as Meadows syndrome seems to be diagnosis of elimination. They point out that a paraclinical balance has to be drawn up very fully on the biological and haemodynamic planes to confirm this condition. Finally, after a short discussion about the therapy, they tackle the problem of the prognosis for life and for future childbearing in these patients, which is determined by the persistence or absence of cardiac enlargement.", "contents": "[Meadows syndrome. A case history (author's transl)]. The authors, having studied a case of Meadows syndrome, confirm that this cardiomyopathy is a specific entity in pregnancy and the puerperium. They point out the difficulties in diagnosis, as Meadows syndrome seems to be diagnosis of elimination. They point out that a paraclinical balance has to be drawn up very fully on the biological and haemodynamic planes to confirm this condition. Finally, after a short discussion about the therapy, they tackle the problem of the prognosis for life and for future childbearing in these patients, which is determined by the persistence or absence of cardiac enlargement."} {"id": "PMID:155124", "title": "Evidences for the existence of glycoproteins and mucopolysaccharides metabolic cycles in the cerebellum of birds and mammals.", "content": "Cerebellum glycoproteins of rats and ducks are studied using sugar-specific agglutinins. It is used the Con A-Peroxidase-DAB technique described by Bernhard and Avrameas (1971). Other agglutinins (Tetragonolobus Purpureus Lectin, Wheat Germ Agglutinin and Soybean Agglutinin) fixed to Peroxidase according to the technique of Gonatas and Avrameas (1973) are also used. The techniques for mucopolysaccharides as described Mart\u00ednez-Rodriguez et al., (1976) are carried out as well. By means of all these techniques, results that suggest the existence of metabolic cycles in Purkinje cells are obtained.", "contents": "Evidences for the existence of glycoproteins and mucopolysaccharides metabolic cycles in the cerebellum of birds and mammals. Cerebellum glycoproteins of rats and ducks are studied using sugar-specific agglutinins. It is used the Con A-Peroxidase-DAB technique described by Bernhard and Avrameas (1971). Other agglutinins (Tetragonolobus Purpureus Lectin, Wheat Germ Agglutinin and Soybean Agglutinin) fixed to Peroxidase according to the technique of Gonatas and Avrameas (1973) are also used. The techniques for mucopolysaccharides as described Mart\u00ednez-Rodriguez et al., (1976) are carried out as well. By means of all these techniques, results that suggest the existence of metabolic cycles in Purkinje cells are obtained."} {"id": "PMID:155125", "title": "Effects of potassium para-aminobenzoate on growth and macromolecule synthesis in fibroblasts cultured from normal and sclerodermatous human skin, and rheumatoid synovial cells.", "content": "Potassium para-aminobenzoate was tested for its ability to affect growth and macromolecule synthesis in vitro using fibroblasts from normal human skin, from affected skin of patients with scleroderma, and rheumatoid synovial cells. The proliferation of all 3 cell types showed dose-dependent inhibition beginning at about 3000 microgram/ml. Acid mucopolysaccharide secretion by rheumatoid synovial cells and scleroderma fibroblasts was inhibited even at 100 microgram/ml, which is within the therapeutic range, and there was over 50% inhibition at 5000 microgram/ml. Collagen synthesis by several different strains, was not affected, despite the use of a range of concentrations and treatment times.", "contents": "Effects of potassium para-aminobenzoate on growth and macromolecule synthesis in fibroblasts cultured from normal and sclerodermatous human skin, and rheumatoid synovial cells. Potassium para-aminobenzoate was tested for its ability to affect growth and macromolecule synthesis in vitro using fibroblasts from normal human skin, from affected skin of patients with scleroderma, and rheumatoid synovial cells. The proliferation of all 3 cell types showed dose-dependent inhibition beginning at about 3000 microgram/ml. Acid mucopolysaccharide secretion by rheumatoid synovial cells and scleroderma fibroblasts was inhibited even at 100 microgram/ml, which is within the therapeutic range, and there was over 50% inhibition at 5000 microgram/ml. Collagen synthesis by several different strains, was not affected, despite the use of a range of concentrations and treatment times."} {"id": "PMID:155128", "title": "Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy.", "content": "Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.", "contents": "Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy. Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes."} {"id": "PMID:155129", "title": "Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro.", "content": "This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction.", "contents": "Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro. This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction."} {"id": "PMID:155130", "title": "Functional disability of geriatric patients in a family medicine program: implications for patient care, education, and research.", "content": "While the elderly comprise a large proportion of patients seen in ambulatory care settings, characteristics of these patients have not been well documented. This paper summarizes results of a survey of functional impairment of elderly patients seen in a family medicine center. Assessments were performed in the areas of social and economic resources, mental health, physical health, and the ability to perform routine activities needed for independent living. Results of the survey suggest that family physicians need to know how to perform a multidimensional functional assessment in order to formulate a comprehensive treatment plan for elderly patients.", "contents": "Functional disability of geriatric patients in a family medicine program: implications for patient care, education, and research. While the elderly comprise a large proportion of patients seen in ambulatory care settings, characteristics of these patients have not been well documented. This paper summarizes results of a survey of functional impairment of elderly patients seen in a family medicine center. Assessments were performed in the areas of social and economic resources, mental health, physical health, and the ability to perform routine activities needed for independent living. Results of the survey suggest that family physicians need to know how to perform a multidimensional functional assessment in order to formulate a comprehensive treatment plan for elderly patients."} {"id": "PMID:155149", "title": "Histoenzymatic and permeability changes in human brain adjacent to meningioma.", "content": "Cerebral specimens were removed from ten patients with meningioma. Vascular permeability was tested with sodium fluorescein and a correlative study of the oxidative and hydrolytic enzyme activity was performed. Vascular permeability change was observed in half of the specimens of cortex taken from the region of the tumor. Labeled tracer diffusion was found to be either perivascular or involved microscopic ischemic areas. Fluorescein diffusion of the edematous white matter was observed in only two specimens. Enzyme activity in walls of the blood vessels was modified in the fluorescent specimens. Alkaline phosphatase and oxidoreductase activities were decreased. Experimental results have shown a relationship between increased vascular permeability and metabolic disorder of both vascular walls and cerebral cortex. Our findings agree with Z\u00fclch's hypothesis regarding a \"hemodynamic\" mechanism in the formation of edema by extraneural compression.", "contents": "Histoenzymatic and permeability changes in human brain adjacent to meningioma. Cerebral specimens were removed from ten patients with meningioma. Vascular permeability was tested with sodium fluorescein and a correlative study of the oxidative and hydrolytic enzyme activity was performed. Vascular permeability change was observed in half of the specimens of cortex taken from the region of the tumor. Labeled tracer diffusion was found to be either perivascular or involved microscopic ischemic areas. Fluorescein diffusion of the edematous white matter was observed in only two specimens. Enzyme activity in walls of the blood vessels was modified in the fluorescent specimens. Alkaline phosphatase and oxidoreductase activities were decreased. Experimental results have shown a relationship between increased vascular permeability and metabolic disorder of both vascular walls and cerebral cortex. Our findings agree with Z\u00fclch's hypothesis regarding a \"hemodynamic\" mechanism in the formation of edema by extraneural compression."} {"id": "PMID:155152", "title": "The utilization of ornithine and citrulline by the growing kitten.", "content": "Previous experiments have demonstrated that cats fed an arginine free purified amino acid diet (-Arg) could be protected from hyperammonemia by the inclusion of ornithine in the diet. Experiments reported here show that diets containing ornithine added at an equimolar (+Orn) or five times equimolar (+5 Orn) to replace arginine in the +Arg basal diet (2.0% Arg . HCl), were incapable of maintenance of body weight. Growing kittens fed a -Arg +Orn and -Arg +5 Orn diets had a daily rate of body weight loss of 6.5 +/- 0.6 and 7.9 +/- 2.2 g, respectively, which is somewhat less than the mean rate of weight loss of kittens fed diets devoid of most of the other amino acids indispensable for the kitten. When citrulline was added to a -Arg diet at an equimolar level to the arginine in the +Arg basal diet, growth rates were equivalent. The mean plasma free ornithine concentration of kittens receiving the -Arg +5 Orn diet was about 33 times higher than when they were fed the +Arg diet. For kittens fed the -Arg + Orn and -Arg +5 Orn diets the mean plasma free arginine was less (but significant only for the -Arg + Orn diet) than that observed for the basal diet. When the -Arg + Cit diet was fed, plasma free arginine concentration was similar and plasma free citrulline was about 18 times higher than when these cats were fed the basal diet.", "contents": "The utilization of ornithine and citrulline by the growing kitten. Previous experiments have demonstrated that cats fed an arginine free purified amino acid diet (-Arg) could be protected from hyperammonemia by the inclusion of ornithine in the diet. Experiments reported here show that diets containing ornithine added at an equimolar (+Orn) or five times equimolar (+5 Orn) to replace arginine in the +Arg basal diet (2.0% Arg . HCl), were incapable of maintenance of body weight. Growing kittens fed a -Arg +Orn and -Arg +5 Orn diets had a daily rate of body weight loss of 6.5 +/- 0.6 and 7.9 +/- 2.2 g, respectively, which is somewhat less than the mean rate of weight loss of kittens fed diets devoid of most of the other amino acids indispensable for the kitten. When citrulline was added to a -Arg diet at an equimolar level to the arginine in the +Arg basal diet, growth rates were equivalent. The mean plasma free ornithine concentration of kittens receiving the -Arg +5 Orn diet was about 33 times higher than when they were fed the +Arg diet. For kittens fed the -Arg + Orn and -Arg +5 Orn diets the mean plasma free arginine was less (but significant only for the -Arg + Orn diet) than that observed for the basal diet. When the -Arg + Cit diet was fed, plasma free arginine concentration was similar and plasma free citrulline was about 18 times higher than when these cats were fed the basal diet."} {"id": "PMID:155154", "title": "Hyperkeratosis palmoplantaris with periodontosis (Papillon-Lefevre syndrome): report of three cases, two occurring in siblings.", "content": "Three cases of palmar-plantar hyperkeratosis with periodontosis, two cases of which occurred in siblings, are reported. The parents were unaffected, and parental consanguinity was present in all three cases. All essential features of the syndrome were present in these cases.", "contents": "Hyperkeratosis palmoplantaris with periodontosis (Papillon-Lefevre syndrome): report of three cases, two occurring in siblings. Three cases of palmar-plantar hyperkeratosis with periodontosis, two cases of which occurred in siblings, are reported. The parents were unaffected, and parental consanguinity was present in all three cases. All essential features of the syndrome were present in these cases."} {"id": "PMID:155158", "title": "Voluntary activation of spindle endings in human muscles temporarily paralysed by nerve pressure.", "content": "1. In normal human subjects, the afferent activity from muscle spindle endings in the pretibial muscles was recorded while a pressure block was applied to the peroneal nerve proximally in the popliteal fossa. 2. In five of ten blocks, spindle activity increased in attempted isometric voluntary contractions when the receptor-bearing muscles were completely paralysed. In the remaining five blocks, voluntary effort still increased spindle activity when maximum voluntary power was reduced by more than 90%, but the ability to activate spindles voluntarily was lost with or slightly before block of the last motor units. When the ability to activate spindle endings in an attempted voluntary contraction was lost sympathetic efferent fibres remained unblocked. 3. It is concluded that the fusimotor effects seen during a voluntary contraction are mediated by myelinated fibres of small calibre which probably innervate intrafusal structures exclusively (gamma fusimotor fibres). There is no necessity to postulate that skeleto-fusimotor (beta) fibres are responsible for the tight 'alpha-gamma co-activation' seen in man during voluntary contractions.", "contents": "Voluntary activation of spindle endings in human muscles temporarily paralysed by nerve pressure. 1. In normal human subjects, the afferent activity from muscle spindle endings in the pretibial muscles was recorded while a pressure block was applied to the peroneal nerve proximally in the popliteal fossa. 2. In five of ten blocks, spindle activity increased in attempted isometric voluntary contractions when the receptor-bearing muscles were completely paralysed. In the remaining five blocks, voluntary effort still increased spindle activity when maximum voluntary power was reduced by more than 90%, but the ability to activate spindles voluntarily was lost with or slightly before block of the last motor units. When the ability to activate spindle endings in an attempted voluntary contraction was lost sympathetic efferent fibres remained unblocked. 3. It is concluded that the fusimotor effects seen during a voluntary contraction are mediated by myelinated fibres of small calibre which probably innervate intrafusal structures exclusively (gamma fusimotor fibres). There is no necessity to postulate that skeleto-fusimotor (beta) fibres are responsible for the tight 'alpha-gamma co-activation' seen in man during voluntary contractions."} {"id": "PMID:155159", "title": "Histochemical reactions of fibres in a fast twitch muscle of the cat.", "content": "1. Serial sections of flexor digitorum longus muscle (f.d.l.) of the cat were examined histochemically for four enzyme systems: adenosine triphosphatase (ATPase) with alkaline and acid pre-incubation, phosphorylase and succinic dehydrogenase (SDHase).2. The number of types into which fibres should be divided was assessed by estimating enzyme reaction intensity from measurements of light transmission through photomicrographs. It was concluded that in general the enzyme reaction intensities of fibres were distributed continuously. However, the distribution histograms showed two (phosphorylase and SDHase) or three (acid and alkaline ATPase) clear peaks. Eighteen combinations of reaction intensities (profiles) were seen of which eight were very rare. The distribution of profiles differed between individuals but were similar in right and left muscles.3. Areas of fibres were measured from muscles which had been fixed at the length at which twitch tension was maximal. The variance in fibre area with any one profile was significantly less than the variance in fibre area of all fibres within a muscle. There were significant differences between the mean areas of fibres with different profiles.4. If only three enzyme reactions are considered (acid and alkaline ATPase and phosphorylase) the majority of fibres fall into one of the three classes commonly accepted for other muscles. The remainder would fit into this classification with the minimal assumption of only one error of fibre typing resulting from the continuous distributions of enzyme reaction intensities. The SDHase reaction was not strongly correlated with the three classes and could be used to divide the fibres further into six groups. Differences between means of fibre areas were significant for all pairs out of these six groups except one.5. The grouping may be considered to reflect a dual system of enzymes, the two systems being (a) ATPases and phosphorylase, (b) SDHase. A possible role of nervous activity in determining this dual system is discussed. The hypothesis involves two partly independent characteristics of motoneuronal activity: (a) the frequency of impulses, and (b) the total number of impulses.6. The measurements are correlated with other physiological variables in the individual animals. The mean areas of fibres in all groups increased with body weight. There were changes in the proportions of light and dark SDHase fibres related to weight. The total area contributed by dark alkaline ATPase fibres decreased and that by intermediate alkaline ATPase fibres increased with increasing twitch time to peak.7. Specific tension of the group of slower muscle fibres in f.d.l. was estimated to be 0.29 N.mm(-2) compared with 0.39 N.mm(-2) for the faster fibres.", "contents": "Histochemical reactions of fibres in a fast twitch muscle of the cat. 1. Serial sections of flexor digitorum longus muscle (f.d.l.) of the cat were examined histochemically for four enzyme systems: adenosine triphosphatase (ATPase) with alkaline and acid pre-incubation, phosphorylase and succinic dehydrogenase (SDHase).2. The number of types into which fibres should be divided was assessed by estimating enzyme reaction intensity from measurements of light transmission through photomicrographs. It was concluded that in general the enzyme reaction intensities of fibres were distributed continuously. However, the distribution histograms showed two (phosphorylase and SDHase) or three (acid and alkaline ATPase) clear peaks. Eighteen combinations of reaction intensities (profiles) were seen of which eight were very rare. The distribution of profiles differed between individuals but were similar in right and left muscles.3. Areas of fibres were measured from muscles which had been fixed at the length at which twitch tension was maximal. The variance in fibre area with any one profile was significantly less than the variance in fibre area of all fibres within a muscle. There were significant differences between the mean areas of fibres with different profiles.4. If only three enzyme reactions are considered (acid and alkaline ATPase and phosphorylase) the majority of fibres fall into one of the three classes commonly accepted for other muscles. The remainder would fit into this classification with the minimal assumption of only one error of fibre typing resulting from the continuous distributions of enzyme reaction intensities. The SDHase reaction was not strongly correlated with the three classes and could be used to divide the fibres further into six groups. Differences between means of fibre areas were significant for all pairs out of these six groups except one.5. The grouping may be considered to reflect a dual system of enzymes, the two systems being (a) ATPases and phosphorylase, (b) SDHase. A possible role of nervous activity in determining this dual system is discussed. The hypothesis involves two partly independent characteristics of motoneuronal activity: (a) the frequency of impulses, and (b) the total number of impulses.6. The measurements are correlated with other physiological variables in the individual animals. The mean areas of fibres in all groups increased with body weight. There were changes in the proportions of light and dark SDHase fibres related to weight. The total area contributed by dark alkaline ATPase fibres decreased and that by intermediate alkaline ATPase fibres increased with increasing twitch time to peak.7. Specific tension of the group of slower muscle fibres in f.d.l. was estimated to be 0.29 N.mm(-2) compared with 0.39 N.mm(-2) for the faster fibres."} {"id": "PMID:155160", "title": "Muscle spindle discharge in normal and obstructed movements.", "content": "1. The discharge activity of muscle spindle endings located in tail and hind limb muscles was recorded during voluntary movements in the cat. 2. During active shortening of the receptor-bearing muscles, both primary and secondary endings tended to fall silent. This was more pronounced, the higher the rate of muscle shortening. We suggest that in unobstructed movements in which muscle velocities exceed 0.2 resting lengths per second (lr/sec), the firing patterns of spindle afferents are dominated by their responses to the length variations. At velocities lower than 0.2 lr/sec, fusimotor action may predominate. 3. When active muscle shortening was unexpectedly halted, both primary and secondary endings resumed firing, but the increases in discharge rate were not as abrupt as might have been expected had there been strong co-activation of fusimotor and skeletomotor neurones. Rather, for the types of movements studied, fusimotor action appears to have been quite modest.", "contents": "Muscle spindle discharge in normal and obstructed movements. 1. The discharge activity of muscle spindle endings located in tail and hind limb muscles was recorded during voluntary movements in the cat. 2. During active shortening of the receptor-bearing muscles, both primary and secondary endings tended to fall silent. This was more pronounced, the higher the rate of muscle shortening. We suggest that in unobstructed movements in which muscle velocities exceed 0.2 resting lengths per second (lr/sec), the firing patterns of spindle afferents are dominated by their responses to the length variations. At velocities lower than 0.2 lr/sec, fusimotor action may predominate. 3. When active muscle shortening was unexpectedly halted, both primary and secondary endings resumed firing, but the increases in discharge rate were not as abrupt as might have been expected had there been strong co-activation of fusimotor and skeletomotor neurones. Rather, for the types of movements studied, fusimotor action appears to have been quite modest."} {"id": "PMID:155161", "title": "[Releasing of plasminogen-activator from the kidney to the blood (author's transl)].", "content": "When fibrinolytic activity in blood samples from various vessels was examined by the dilute-blood-clotlysis-time method (DBCLT), it was found to be noticeably high in the renal venous blood, though the activity was not detected by usual blood clotlysis time method. Plasmin was not detected in any blood samples examined, and the contents of fibrinogen and fibrin (or fibrinogen) breakdown products in the renal venous blood were not significantly different from those in the blood from other vessels. However, the high activity of plasminogen-activator was found only in the renal venous blood. Inhibitors on plasmin and plasminogen-activator (urokinase) were detected in almost the same amount in the blood samples from the various vessels. The amount of the inhibitors was sufficient to inhibit the plasminogen activation by urokinase, whose activity was equivalent to the plasminogen-activator activity in the renal venous blood. These results indicate that the high activity by DBCLT in the renal venous blood was derived from the high activity of plasminogen-activator, which was inactivated by inhibitors in undiluted blood. Plasminogen-activator may be released from the kidney to the blood, and immediately inactivated by the inhibitors in renal vein, and then diluted with systemic blood which contains little plasminogen-activator.", "contents": "[Releasing of plasminogen-activator from the kidney to the blood (author's transl)]. When fibrinolytic activity in blood samples from various vessels was examined by the dilute-blood-clotlysis-time method (DBCLT), it was found to be noticeably high in the renal venous blood, though the activity was not detected by usual blood clotlysis time method. Plasmin was not detected in any blood samples examined, and the contents of fibrinogen and fibrin (or fibrinogen) breakdown products in the renal venous blood were not significantly different from those in the blood from other vessels. However, the high activity of plasminogen-activator was found only in the renal venous blood. Inhibitors on plasmin and plasminogen-activator (urokinase) were detected in almost the same amount in the blood samples from the various vessels. The amount of the inhibitors was sufficient to inhibit the plasminogen activation by urokinase, whose activity was equivalent to the plasminogen-activator activity in the renal venous blood. These results indicate that the high activity by DBCLT in the renal venous blood was derived from the high activity of plasminogen-activator, which was inactivated by inhibitors in undiluted blood. Plasminogen-activator may be released from the kidney to the blood, and immediately inactivated by the inhibitors in renal vein, and then diluted with systemic blood which contains little plasminogen-activator."} {"id": "PMID:155167", "title": "Response of physicians to medical complaints in men and women.", "content": "Workups by physicians in response to five common complaints in a sample of 104 men and women--52 married couples--were evaluated by chart audit. For the total group of complaints, back pain, headache, dizziness, chest pain, and fatigue, the physicians' workups were significantly more extensive for men than they were for women. These data tend to support the argument that male physicians take medical illness more seriously in men than in women.", "contents": "Response of physicians to medical complaints in men and women. Workups by physicians in response to five common complaints in a sample of 104 men and women--52 married couples--were evaluated by chart audit. For the total group of complaints, back pain, headache, dizziness, chest pain, and fatigue, the physicians' workups were significantly more extensive for men than they were for women. These data tend to support the argument that male physicians take medical illness more seriously in men than in women."} {"id": "PMID:155170", "title": "Literature survey of bacterial, fungal, and Drosophila assay systems used in the evaluation of selected chemical compounds for mutagenic activity.", "content": "Literature reports were surveyed, with results noted from experiments in seven nonmammalian assay systems used for the detection of mutagenicity or other related genetic effects. A comparison was made of the activities of 54 selected noncarcinogens, procarcinogens, and ultimate carcinogens as revealed by these test systems. Of the compounds tested, 49 (91%) were active in one or more of the assays, and 42 (78%) were positive in at least one system without having to be metabolically activated. In one or more test systems, 17/17 (100%) of the ultimate carcinogens, 27/28 (96%) of the procarcinogens, and 6/9 (67%) of the noncarcinogens were positive. The Ames Salmonella-microsome assay responded with increased mutation frequency to 37/44 (84%) of the carcinogenic compounds but to only 2/8 (25%) of the noncarcinogens tested. The Drosophila system responded to 19/21 (90%) of the carcinogens and to 3/6 (50%) of the noncarcinogens. Prophages were induced when lysogenic bacteria were exposed to 12/21 (57%) of the carcinogens, but not enough tests were done with the noncarcinogens (1/3, or 33%) for a comparison. The other systems reviewed, such as the killing of repair-deficient bacteria, mutations in Escherichia coli and Neurospora crassa, and the host-mediated assay, were not challenged by enough of the compounds for valid comparisons.", "contents": "Literature survey of bacterial, fungal, and Drosophila assay systems used in the evaluation of selected chemical compounds for mutagenic activity. Literature reports were surveyed, with results noted from experiments in seven nonmammalian assay systems used for the detection of mutagenicity or other related genetic effects. A comparison was made of the activities of 54 selected noncarcinogens, procarcinogens, and ultimate carcinogens as revealed by these test systems. Of the compounds tested, 49 (91%) were active in one or more of the assays, and 42 (78%) were positive in at least one system without having to be metabolically activated. In one or more test systems, 17/17 (100%) of the ultimate carcinogens, 27/28 (96%) of the procarcinogens, and 6/9 (67%) of the noncarcinogens were positive. The Ames Salmonella-microsome assay responded with increased mutation frequency to 37/44 (84%) of the carcinogenic compounds but to only 2/8 (25%) of the noncarcinogens tested. The Drosophila system responded to 19/21 (90%) of the carcinogens and to 3/6 (50%) of the noncarcinogens. Prophages were induced when lysogenic bacteria were exposed to 12/21 (57%) of the carcinogens, but not enough tests were done with the noncarcinogens (1/3, or 33%) for a comparison. The other systems reviewed, such as the killing of repair-deficient bacteria, mutations in Escherichia coli and Neurospora crassa, and the host-mediated assay, were not challenged by enough of the compounds for valid comparisons."} {"id": "PMID:155174", "title": "[Distribution of the electrocardiographic changes characteristic of ischemic heart disease among the male population of Leningrad in comparison with the clinical biochemical indices].", "content": "The authors studied the peculiarities of electrocardiograms recorded under conditions of rest in 1,022 males from 40 to 59 years of age, who reflected representatively a selected unorganized population of 1,250 persons. The ECG were analysed according to the Minnesota code. Among the examined persons 9.6% were found to have \"coronary\" ECG changes indicating to ischemic heart disease. The tread-mill test conducted in individuals chosen for scrupulous examination made it possible to make a diagnosis of ischemic heart disease in 19.6% of 219 persons (72 of whom had hyperlipidemia). A tendency toward relative decrease in high-density lipoproteins was noted in individuals with clearly manifested signs of coronary pathology on the ECG.", "contents": "[Distribution of the electrocardiographic changes characteristic of ischemic heart disease among the male population of Leningrad in comparison with the clinical biochemical indices]. The authors studied the peculiarities of electrocardiograms recorded under conditions of rest in 1,022 males from 40 to 59 years of age, who reflected representatively a selected unorganized population of 1,250 persons. The ECG were analysed according to the Minnesota code. Among the examined persons 9.6% were found to have \"coronary\" ECG changes indicating to ischemic heart disease. The tread-mill test conducted in individuals chosen for scrupulous examination made it possible to make a diagnosis of ischemic heart disease in 19.6% of 219 persons (72 of whom had hyperlipidemia). A tendency toward relative decrease in high-density lipoproteins was noted in individuals with clearly manifested signs of coronary pathology on the ECG."} {"id": "PMID:155177", "title": "Integrating the physically handicapped child.", "content": "This paper will serve several purposes: (1) to provide information on the incidence of physically handicapped children (exclusive of the blind and deaf) who are likely to be integrated into schools for normal non-physically impaired children, (2) to describe briefly the major handicapping conditions and their educational implications, (3) to comment on why integration has come about and why it promises to enrich the lives of normal children, (4) to suggest how physicians, physical therapists, and occupational therapists might help to make schools programs successful, (5) to comment briefly on financial implications of this program and to suggest ways in which the complexity of the medical management might be simplified, (6) to provide factual knowledge about the handicapped child and his potential to teachers who are already on the firing line to \"improve\" the academic achievement of the alleged normal child.", "contents": "Integrating the physically handicapped child. This paper will serve several purposes: (1) to provide information on the incidence of physically handicapped children (exclusive of the blind and deaf) who are likely to be integrated into schools for normal non-physically impaired children, (2) to describe briefly the major handicapping conditions and their educational implications, (3) to comment on why integration has come about and why it promises to enrich the lives of normal children, (4) to suggest how physicians, physical therapists, and occupational therapists might help to make schools programs successful, (5) to comment briefly on financial implications of this program and to suggest ways in which the complexity of the medical management might be simplified, (6) to provide factual knowledge about the handicapped child and his potential to teachers who are already on the firing line to \"improve\" the academic achievement of the alleged normal child."} {"id": "PMID:155179", "title": "Administrative concerns and schools' relationship with private practicing physicians.", "content": "In this discussion of four administrative concerns, there has been an effort to suggest school-sponsored activities leading to close productive relationships with community physicians and optimum use of medical information available for maintaining adequate medical component in the school management of children with handicapping conditions. A recurring theme is that to attack these concerns, there must be administrative leadership which sees them as important and knowledgeable staff members who are available, assigned and supported to perform the necessary task.", "contents": "Administrative concerns and schools' relationship with private practicing physicians. In this discussion of four administrative concerns, there has been an effort to suggest school-sponsored activities leading to close productive relationships with community physicians and optimum use of medical information available for maintaining adequate medical component in the school management of children with handicapping conditions. A recurring theme is that to attack these concerns, there must be administrative leadership which sees them as important and knowledgeable staff members who are available, assigned and supported to perform the necessary task."} {"id": "PMID:155181", "title": "Modulator binding protein antagonizes activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport of red blood cell membranes.", "content": "Red blood cells contain a protein that activates membrane-bound (Ca2+ + Mg2+)-ATPase and Ca2+ transport. The red blood cell activator protein is similar to a modulator protein that stimulates cyclic AMP phosphodiesterase. Wang and Desai [Journal of Biological Chemistry 252:4175--4184, 1977] described a modulator-binding protein that antagonizes the activation of cyclic AMP phosphodiesterase by modulator protein. In the present work, modulator-binding protein was shown to antagonize the activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport by red blood cell activator protein. The results further demonstrate the similarity between the activator protein from human red blood cells and the modulator protein from bovine brain.", "contents": "Modulator binding protein antagonizes activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport of red blood cell membranes. Red blood cells contain a protein that activates membrane-bound (Ca2+ + Mg2+)-ATPase and Ca2+ transport. The red blood cell activator protein is similar to a modulator protein that stimulates cyclic AMP phosphodiesterase. Wang and Desai [Journal of Biological Chemistry 252:4175--4184, 1977] described a modulator-binding protein that antagonizes the activation of cyclic AMP phosphodiesterase by modulator protein. In the present work, modulator-binding protein was shown to antagonize the activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport by red blood cell activator protein. The results further demonstrate the similarity between the activator protein from human red blood cells and the modulator protein from bovine brain."} {"id": "PMID:155182", "title": "Dacron patch enlargement of anterior wall of left ventricle after aneurysmectomy with concomitant infarctectomy.", "content": "The basis for left ventricular aneurysmectomy with cardiopulmonary bypass was established 20 years ago. There is a higher risk in patients who undergo operation within 2 months of myocardial infarction. In these patients there may be no clear demarcation between devitalized tissue and residual healthy myocardium. A case is reported in which anterolateral aneurysmectomy with concomitant infarctectomy so compromised left ventricular size that the anterolateral wall of the left ventricle had to be reconstructed with a Dacron patch graft.", "contents": "Dacron patch enlargement of anterior wall of left ventricle after aneurysmectomy with concomitant infarctectomy. The basis for left ventricular aneurysmectomy with cardiopulmonary bypass was established 20 years ago. There is a higher risk in patients who undergo operation within 2 months of myocardial infarction. In these patients there may be no clear demarcation between devitalized tissue and residual healthy myocardium. A case is reported in which anterolateral aneurysmectomy with concomitant infarctectomy so compromised left ventricular size that the anterolateral wall of the left ventricle had to be reconstructed with a Dacron patch graft."} {"id": "PMID:155196", "title": "[Embolism caused by a fiber from a synthetic vascular prosthesis].", "content": "Authors report on an embolization due to synthetic thread following inplantation of a vascular prosthesis, demonstrated by means of polarization optics in the spleen, corresponding to the dacron threads of the prosthesis. Complications of that type following vascular operations should be taken into account.", "contents": "[Embolism caused by a fiber from a synthetic vascular prosthesis]. Authors report on an embolization due to synthetic thread following inplantation of a vascular prosthesis, demonstrated by means of polarization optics in the spleen, corresponding to the dacron threads of the prosthesis. Complications of that type following vascular operations should be taken into account."} {"id": "PMID:155192", "title": "[Classification of electrocardiographic patterns by full machine descriptions of the electrocardiograms].", "content": "To classify the electrograms due to their complete, computer-produced description, an algorithm for automatic formation of electrocardiographic inference, is offered. Some results reached with this algorithm in solution of practical problems met in electrocardiographic diagnosis were presented.", "contents": "[Classification of electrocardiographic patterns by full machine descriptions of the electrocardiograms]. To classify the electrograms due to their complete, computer-produced description, an algorithm for automatic formation of electrocardiographic inference, is offered. Some results reached with this algorithm in solution of practical problems met in electrocardiographic diagnosis were presented."} {"id": "PMID:155197", "title": "Relationship between specialized cells, capillaries and intermediary cytofibrillary elements. XIth note. Biological evolution of the emunctory subsystem and stereotype in vertebrates.", "content": "This note completes in vertebrates the study of the emunctory subsystem and stereotype in invertebrates (Xth note). The theory of systems (and of open biological systems) of Bertalanffy, the theory of internal laws and limits of each organizational level (Needham) and the theory of biological stereotypes and of their morphofunctional expression (M\u00e2rza, Repciuc and Eskenasy) are also corroborated. In this light there were studied: the characters of the emunctory stereotype in vertebrates, its similar formation mode by three links (extracting, conveying and excretory links) as in the coelomatous invertebrates, and the passage of the emunctory stereotype from invertebrates to vertebrates. The present-day Acraniata and their offsprings, the Protocraniata, Agnatha and aquatic Gnathostoma, have an emunctory stereotype identical in its essential characters, without discrepancies between its links. The passage does not occur, however, from the metanephridia to the pronephros, but to the mesonephros. This latter reaches its highest functional limits in Dipnoi and Amphibia. The author indicates the mechanisms which, in its opinion, play a role in the activation of organo-genetic capacities of the metanephros in the caudal nephrogenic area. The importance of the three nephrogenic areas of the vertebrates, their succession and interdependence are also discussed. The problem of the archi(holo)nephros is critically reviewed, and the author's hypothesis that the glomerular ultrafiltrate and the coelomic liquid of invertebrates with metanephridia had the same composition and underwent the same processes of reabsorption-secretion is dwelt upon. A conclusion is drawn from these two notes, according to which stability--directed by the stabilizing selection--plays a directional role in the evolution of the new organizational levels, in the maintenance and development of the characters of the emunctory stereotype within the emunctory subsystem (EMSS). Between variability and stability strong relations are established and hereditarily transmitted.", "contents": "Relationship between specialized cells, capillaries and intermediary cytofibrillary elements. XIth note. Biological evolution of the emunctory subsystem and stereotype in vertebrates. This note completes in vertebrates the study of the emunctory subsystem and stereotype in invertebrates (Xth note). The theory of systems (and of open biological systems) of Bertalanffy, the theory of internal laws and limits of each organizational level (Needham) and the theory of biological stereotypes and of their morphofunctional expression (M\u00e2rza, Repciuc and Eskenasy) are also corroborated. In this light there were studied: the characters of the emunctory stereotype in vertebrates, its similar formation mode by three links (extracting, conveying and excretory links) as in the coelomatous invertebrates, and the passage of the emunctory stereotype from invertebrates to vertebrates. The present-day Acraniata and their offsprings, the Protocraniata, Agnatha and aquatic Gnathostoma, have an emunctory stereotype identical in its essential characters, without discrepancies between its links. The passage does not occur, however, from the metanephridia to the pronephros, but to the mesonephros. This latter reaches its highest functional limits in Dipnoi and Amphibia. The author indicates the mechanisms which, in its opinion, play a role in the activation of organo-genetic capacities of the metanephros in the caudal nephrogenic area. The importance of the three nephrogenic areas of the vertebrates, their succession and interdependence are also discussed. The problem of the archi(holo)nephros is critically reviewed, and the author's hypothesis that the glomerular ultrafiltrate and the coelomic liquid of invertebrates with metanephridia had the same composition and underwent the same processes of reabsorption-secretion is dwelt upon. A conclusion is drawn from these two notes, according to which stability--directed by the stabilizing selection--plays a directional role in the evolution of the new organizational levels, in the maintenance and development of the characters of the emunctory stereotype within the emunctory subsystem (EMSS). Between variability and stability strong relations are established and hereditarily transmitted."} {"id": "PMID:155198", "title": "6-Aminonicotinamide-induced eye defects in rats.", "content": "The pathological changes and structural anomalies induced by 6-aminonicotinamide (6-AN) in the developing eye were studied in rats (Wistar and hooded randombred strain). The substance was administered in aqueous solution intraperitoneally (4 mg/kg on day 9--10 of pregnancy: 5 mg/kg on day 11 of pregnancy; 8 mg/kg on day 13--17 of pregnancy) and in physiological saline intraamniotically (0.01 ml of a 1% solution in physiological saline on day 15 of pregnancy). Embryos and foetuses from experimental series and from untreated control series were macro- and microscopically examined on day 10--20 of pregnancy. Control foetuses from mothers injected with distilled water on day 9--17 of pregnancy were examined on day 20 of pregnancy. The pathological changes and structural anomalies detected at successive developmental stages are presented. They reveal an obvious phase specificity and attest that the same substance may act through both of the main teratogenic pathways hypothetically put forward by Menkes et al. (1970). Based upon the present findings (and some previous results obtained in experiments with bisazo dyes) a working hypothesis is tentatively presented, as to the possible determination of the uni- or/and bilateral distribution of chemically induced developmental defects. In connection with some reversible or transitory pathological changes the role of recovery in teratogenesis is pointed out.", "contents": "6-Aminonicotinamide-induced eye defects in rats. The pathological changes and structural anomalies induced by 6-aminonicotinamide (6-AN) in the developing eye were studied in rats (Wistar and hooded randombred strain). The substance was administered in aqueous solution intraperitoneally (4 mg/kg on day 9--10 of pregnancy: 5 mg/kg on day 11 of pregnancy; 8 mg/kg on day 13--17 of pregnancy) and in physiological saline intraamniotically (0.01 ml of a 1% solution in physiological saline on day 15 of pregnancy). Embryos and foetuses from experimental series and from untreated control series were macro- and microscopically examined on day 10--20 of pregnancy. Control foetuses from mothers injected with distilled water on day 9--17 of pregnancy were examined on day 20 of pregnancy. The pathological changes and structural anomalies detected at successive developmental stages are presented. They reveal an obvious phase specificity and attest that the same substance may act through both of the main teratogenic pathways hypothetically put forward by Menkes et al. (1970). Based upon the present findings (and some previous results obtained in experiments with bisazo dyes) a working hypothesis is tentatively presented, as to the possible determination of the uni- or/and bilateral distribution of chemically induced developmental defects. In connection with some reversible or transitory pathological changes the role of recovery in teratogenesis is pointed out."} {"id": "PMID:155199", "title": "Differentiation of human anterior hypophysial cells during fetal life.", "content": "This paper deals with cell differentiation in the anterior hypophysis of the human fetus, as may be stated by electronmicroscopy. In the 9 cm fetus the greater number of cells are devoid of granules; this was the reason for their being considered as nondifferentiated cells. A small number of cells however contain granules which vary from cell to cell in number and size and may be considered as cells with different functions. Usually the granules secreted within the same cell have very close diameters. The number of such cells increases with the age of the fetus; thus, in 170 mm fetal length there remain very few nondifferentiated cells. Some cells have their granules located centrally, while in others they are closer to the cell membrane, suggesting that the product of cell secretion is extruded in the nearby lumen of capillaries. The shape of the cells, their location, as well as the features of the cell organelles are similar to those described for adults, but in the fetus they are proportionally fewer. The electronmicroscopic pattern does not seem to be a sufficient criterion for the specification of the type of cells, except ACTH-MSH secreting cells.", "contents": "Differentiation of human anterior hypophysial cells during fetal life. This paper deals with cell differentiation in the anterior hypophysis of the human fetus, as may be stated by electronmicroscopy. In the 9 cm fetus the greater number of cells are devoid of granules; this was the reason for their being considered as nondifferentiated cells. A small number of cells however contain granules which vary from cell to cell in number and size and may be considered as cells with different functions. Usually the granules secreted within the same cell have very close diameters. The number of such cells increases with the age of the fetus; thus, in 170 mm fetal length there remain very few nondifferentiated cells. Some cells have their granules located centrally, while in others they are closer to the cell membrane, suggesting that the product of cell secretion is extruded in the nearby lumen of capillaries. The shape of the cells, their location, as well as the features of the cell organelles are similar to those described for adults, but in the fetus they are proportionally fewer. The electronmicroscopic pattern does not seem to be a sufficient criterion for the specification of the type of cells, except ACTH-MSH secreting cells."} {"id": "PMID:155200", "title": "Histopathology of thyroid carcinoma. A review of 500 cases.", "content": "A lot of 500 thyroid cancers were studied. The following histological aspects were found: folliculo-papillary carcinoma (60.6%), follicular carcinoma (20.6%), anaplastic carcinoma (15,4%), medullary carcinoma (3.2%), malignant lymphoma (0.2%). The sex distribution showed a strong predominance of women as compared to men, in a ratio of 3/1. The highest incidence appeared between 30 and 50 years of age. The histopathological and cytological features in fine needle biopsy are discussed.", "contents": "Histopathology of thyroid carcinoma. A review of 500 cases. A lot of 500 thyroid cancers were studied. The following histological aspects were found: folliculo-papillary carcinoma (60.6%), follicular carcinoma (20.6%), anaplastic carcinoma (15,4%), medullary carcinoma (3.2%), malignant lymphoma (0.2%). The sex distribution showed a strong predominance of women as compared to men, in a ratio of 3/1. The highest incidence appeared between 30 and 50 years of age. The histopathological and cytological features in fine needle biopsy are discussed."} {"id": "PMID:155201", "title": "Morphopathologic changes of enteropathies in 161 children's intestinal endobiopsies.", "content": "The authors examined microscopically 161 jejunal biopsies of which 142 presented a pathologic mucosa. The two sexes were equally represented and the prevalent age was between 1 and 2 years. Nearly one third of the cases were acute enteritides and the remaining ones--granulative and atrophic enteritides; none of them was hypertrophic. The causes of these enteropathies are various.", "contents": "Morphopathologic changes of enteropathies in 161 children's intestinal endobiopsies. The authors examined microscopically 161 jejunal biopsies of which 142 presented a pathologic mucosa. The two sexes were equally represented and the prevalent age was between 1 and 2 years. Nearly one third of the cases were acute enteritides and the remaining ones--granulative and atrophic enteritides; none of them was hypertrophic. The causes of these enteropathies are various."} {"id": "PMID:155204", "title": "Sister chromatid exchange detection. The method and its usefulness in genetic counseling.", "content": "The sister chromatid exchange (SCE) detection was performed in the blood cultures from two human subjects, progenitors of some congenitally malformed children and from one patient with presumed symptoms of Bloom's syndrome. The usefulness of the SCE detection in genetic counseling and for the estimation of induced chromosomal lesions is discussed.", "contents": "Sister chromatid exchange detection. The method and its usefulness in genetic counseling. The sister chromatid exchange (SCE) detection was performed in the blood cultures from two human subjects, progenitors of some congenitally malformed children and from one patient with presumed symptoms of Bloom's syndrome. The usefulness of the SCE detection in genetic counseling and for the estimation of induced chromosomal lesions is discussed."} {"id": "PMID:155205", "title": "Investigations on the action of neurotoxic agents present in the urine of patients suffering from hepatitis. (Biological test).", "content": "Injecting urine obtained from patients suffering from hepatitis (acute and chronic-active), into the dorsal lymph sac of 336 frogs, the authors repeatedly observed serious motor disturbances, which caused the death of animals, in proportion of 66%. Histologically, in the treated animals grave neuronal lesions appear (reaching sclerosis and disintegration of motor neurons) at the level of the midbrain, pons and medulla oblongata, attaining the highest degree in the motor zones of the ventral horns, of the spinal cord. In the control group (200 frogs), treated in the same manner with urine originating from healthy persons, the mortality was only 6%. It is concluded that in the active stage of hepatites, in the urine of the patients cytolytic substances of a definite neurotoxic action appear, which is manifest by motor disorders and grave dystrophic lesions of the brainstem and spinal cord.", "contents": "Investigations on the action of neurotoxic agents present in the urine of patients suffering from hepatitis. (Biological test). Injecting urine obtained from patients suffering from hepatitis (acute and chronic-active), into the dorsal lymph sac of 336 frogs, the authors repeatedly observed serious motor disturbances, which caused the death of animals, in proportion of 66%. Histologically, in the treated animals grave neuronal lesions appear (reaching sclerosis and disintegration of motor neurons) at the level of the midbrain, pons and medulla oblongata, attaining the highest degree in the motor zones of the ventral horns, of the spinal cord. In the control group (200 frogs), treated in the same manner with urine originating from healthy persons, the mortality was only 6%. It is concluded that in the active stage of hepatites, in the urine of the patients cytolytic substances of a definite neurotoxic action appear, which is manifest by motor disorders and grave dystrophic lesions of the brainstem and spinal cord."} {"id": "PMID:155209", "title": "[Fine-structure and function of the primary proliferative layer of the embryonal central nervous system].", "content": "Results obtained by mechanical isolation of neuroblasts from the primary proliferative layer of the central nervous system in chick embryos by the aid of an original method and by electronmicroscopic investigations are consistent with Sauer's concept on neuroepithelial cell proliferation. The bipolar form of the undifferentiated neuroblast is maintained--at the beginning--by external factors of cell contact only. Each end-feet contains two centrioles, one of which represents the basal body of a cilium. During mitosis, the position parallel to the lumen of the spingle axis and the subsequent appearance of two identical daughter cells depend on the behaviour of the centrioles. The later may move in an abnormal direction, and induce thus an obliquely or perpendicularly laying spindle axis. These changes may influence--on the other hand--the mechanism of proliferation.", "contents": "[Fine-structure and function of the primary proliferative layer of the embryonal central nervous system]. Results obtained by mechanical isolation of neuroblasts from the primary proliferative layer of the central nervous system in chick embryos by the aid of an original method and by electronmicroscopic investigations are consistent with Sauer's concept on neuroepithelial cell proliferation. The bipolar form of the undifferentiated neuroblast is maintained--at the beginning--by external factors of cell contact only. Each end-feet contains two centrioles, one of which represents the basal body of a cilium. During mitosis, the position parallel to the lumen of the spingle axis and the subsequent appearance of two identical daughter cells depend on the behaviour of the centrioles. The later may move in an abnormal direction, and induce thus an obliquely or perpendicularly laying spindle axis. These changes may influence--on the other hand--the mechanism of proliferation."} {"id": "PMID:155219", "title": "Immunocompetence of patients with transitional cell carcinoma as measured by dinitrochlorobenzene skin tests and in vitro lymphocyte function.", "content": "Patients with transitional cell carcinoma of the bladder have a highly significant stepwise decrease in responsiveness to challenge with DNCB with advancing stage of disease. Seventy-five percent of those patients with superficial tumors are skin-test positive versus only 35% for those having tumors that are locally advanced and/or metastatic. MLC response and ability to stimulate in this culture as well as PHA and Con A response of blood leukocytes have been studied in relation to stage of disease and therapy. Recent irradiation appears to inhibit significantly MLC responsiveness, and PHA and Con A blastogenesis. Although responsiveness for this group of patients is decreased from normal, a further decrease occurs in responsiveness to Con A with advancing stage of disease. Blood leukocytes from some patients with urinary bladder carcinoma appear to have a decreased ability to function as stimulator cells in one-way MLC. This ability to stimulate returns to normal levels with tumor removal.", "contents": "Immunocompetence of patients with transitional cell carcinoma as measured by dinitrochlorobenzene skin tests and in vitro lymphocyte function. Patients with transitional cell carcinoma of the bladder have a highly significant stepwise decrease in responsiveness to challenge with DNCB with advancing stage of disease. Seventy-five percent of those patients with superficial tumors are skin-test positive versus only 35% for those having tumors that are locally advanced and/or metastatic. MLC response and ability to stimulate in this culture as well as PHA and Con A response of blood leukocytes have been studied in relation to stage of disease and therapy. Recent irradiation appears to inhibit significantly MLC responsiveness, and PHA and Con A blastogenesis. Although responsiveness for this group of patients is decreased from normal, a further decrease occurs in responsiveness to Con A with advancing stage of disease. Blood leukocytes from some patients with urinary bladder carcinoma appear to have a decreased ability to function as stimulator cells in one-way MLC. This ability to stimulate returns to normal levels with tumor removal."} {"id": "PMID:155220", "title": "In vitro immune parameters in relation to clinical course in transitional cell carcinoma.", "content": "Longitudinal experiments were performed in which lymphocytes from patients were compared with simultaneously studied normals. Patient lymphocytes were examined for their ability to function as stimulator and responder cells in a one-way MLC. Additionally, lymphocyte mitogenic response to PHA and Con A were examined. We observed changes in these parameters that could be correlated with the clinical course of the patients.", "contents": "In vitro immune parameters in relation to clinical course in transitional cell carcinoma. Longitudinal experiments were performed in which lymphocytes from patients were compared with simultaneously studied normals. Patient lymphocytes were examined for their ability to function as stimulator and responder cells in a one-way MLC. Additionally, lymphocyte mitogenic response to PHA and Con A were examined. We observed changes in these parameters that could be correlated with the clinical course of the patients."} {"id": "PMID:155221", "title": "Mixed leukocyte culture reactivity of lymph node cells regional to transitional cell carcinoma of the bladder.", "content": "Regional lymph node cells from some patients with bladder cancer exhibited a suppressive effect on the ability of autologous and allogeneic blood leukocytes to function as stimulator cells in one-way mixed leukocyte culture. The appearance of the suppressor activity was significantly correlated to advancing stage of disease and to the histology of the regional lymph nodes.", "contents": "Mixed leukocyte culture reactivity of lymph node cells regional to transitional cell carcinoma of the bladder. Regional lymph node cells from some patients with bladder cancer exhibited a suppressive effect on the ability of autologous and allogeneic blood leukocytes to function as stimulator cells in one-way mixed leukocyte culture. The appearance of the suppressor activity was significantly correlated to advancing stage of disease and to the histology of the regional lymph nodes."} {"id": "PMID:155223", "title": "Effect of p-chlorophenylalanine on avoidance learning of two differentially housed mouse strains.", "content": "The effect of p-chlorophenylalanine (PCPA) has been studied on the acquisition of avoidance learning and on brain concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and tryptophan of differentially housed male mice of Albino Swiss and DBA strains. The results obtained do not support the hypothesis that learning ability varies inversely with the concentration of brain 5-hydroxytryptamine. PCPA can appear as influencing learning ability of different strains of mice differentially housed, depending more on the emotional baseline of the animals than on brain 5-hydroxytryptamine modification.", "contents": "Effect of p-chlorophenylalanine on avoidance learning of two differentially housed mouse strains. The effect of p-chlorophenylalanine (PCPA) has been studied on the acquisition of avoidance learning and on brain concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and tryptophan of differentially housed male mice of Albino Swiss and DBA strains. The results obtained do not support the hypothesis that learning ability varies inversely with the concentration of brain 5-hydroxytryptamine. PCPA can appear as influencing learning ability of different strains of mice differentially housed, depending more on the emotional baseline of the animals than on brain 5-hydroxytryptamine modification."} {"id": "PMID:155228", "title": "[Effect of an adrenergic-parasympatholytic aerosol combination on the respiratory function].", "content": "The ventilatory and cardiocirculatory effects of salbutamol-ipratropium aerosol were examined in 27 subjects with bronchial obstruction. The activity of the association was compared with that of the two components at therapeutic doses. Then the effects and possible side-effects of the association were assessed at increasing doses. Lastly, the association was compared with its components. The association had the same latency time, but a more prolonged effect (still effective after 120'), when compared with salbutamol. It was decidedly superior to the parasympatholytic. No side-effects of any kind were observed.", "contents": "[Effect of an adrenergic-parasympatholytic aerosol combination on the respiratory function]. The ventilatory and cardiocirculatory effects of salbutamol-ipratropium aerosol were examined in 27 subjects with bronchial obstruction. The activity of the association was compared with that of the two components at therapeutic doses. Then the effects and possible side-effects of the association were assessed at increasing doses. Lastly, the association was compared with its components. The association had the same latency time, but a more prolonged effect (still effective after 120'), when compared with salbutamol. It was decidedly superior to the parasympatholytic. No side-effects of any kind were observed."} {"id": "PMID:155236", "title": "Cell-mediated immune response to dog pulp tissue altered by Grossman's formula sealer via the root canal.", "content": "Pulp tissue from three experimental dogs was tested for its antigenicity before and after incubation with Grossman's formula sealer (GS). Cellmediated skin-test reactions showed an increased response to pulp that had been incubated in Grossman's formula sealer, washed, and then injected as compared with pulp or GS alone. In vitro analysis of cell-mediated immune response (lymphocyte proliferation) showed a marked increase when pulp tissue was incubated in GS and washed as compared to saline-treated pulp. Comparing the saline-incubated pulp to the GS-altered pulp revealed that the increase in radioactivity was statistically significant at p less than 0.0001. Therefore, Grossman's formula sealer altered dog pulp tissue and rendered it antigenically active, and a specific cell-mediated lymphocyte response was produced.", "contents": "Cell-mediated immune response to dog pulp tissue altered by Grossman's formula sealer via the root canal. Pulp tissue from three experimental dogs was tested for its antigenicity before and after incubation with Grossman's formula sealer (GS). Cellmediated skin-test reactions showed an increased response to pulp that had been incubated in Grossman's formula sealer, washed, and then injected as compared with pulp or GS alone. In vitro analysis of cell-mediated immune response (lymphocyte proliferation) showed a marked increase when pulp tissue was incubated in GS and washed as compared to saline-treated pulp. Comparing the saline-incubated pulp to the GS-altered pulp revealed that the increase in radioactivity was statistically significant at p less than 0.0001. Therefore, Grossman's formula sealer altered dog pulp tissue and rendered it antigenically active, and a specific cell-mediated lymphocyte response was produced."} {"id": "PMID:155240", "title": "Genetic counseling and the pediatrician.", "content": "The assistance of the pediatrician, following diagnosis of a child with a genetic disorder, towards his family consists today in giving genetic counseling for prevention of recurrence in future pregnancies. The process of genetic counseling, once the right diagnosis is made, should not be difficult as concerns Mendelian inheritance. It is well known that several chromosomal disorders follow the rules of Mendelian inheritance. The theory of polygenic or multifactorial inheritance may create problems in the accurate estimation of risks. An effort is made to discover the mechanisms of genetic \"predisposition\" or the adverse environmental factors, in order to minimize the occurrence of such disorders. An important tool in prevention of several genetic disorders, which should be mentioned in genetic counseling, is prenatal diagnosis.", "contents": "Genetic counseling and the pediatrician. The assistance of the pediatrician, following diagnosis of a child with a genetic disorder, towards his family consists today in giving genetic counseling for prevention of recurrence in future pregnancies. The process of genetic counseling, once the right diagnosis is made, should not be difficult as concerns Mendelian inheritance. It is well known that several chromosomal disorders follow the rules of Mendelian inheritance. The theory of polygenic or multifactorial inheritance may create problems in the accurate estimation of risks. An effort is made to discover the mechanisms of genetic \"predisposition\" or the adverse environmental factors, in order to minimize the occurrence of such disorders. An important tool in prevention of several genetic disorders, which should be mentioned in genetic counseling, is prenatal diagnosis."} {"id": "PMID:155241", "title": "Common skin problems in the pediatric office.", "content": "Skin diseases represent a major problem in everyday practice. This article discusses the most common dermatological entities as seen in the pediatrician's office with practical guidelines for their therapy. Acne, eczema, diaper rash, verruca vulgaris, impetigo and skin infestations are among those topics discussed.", "contents": "Common skin problems in the pediatric office. Skin diseases represent a major problem in everyday practice. This article discusses the most common dermatological entities as seen in the pediatrician's office with practical guidelines for their therapy. Acne, eczema, diaper rash, verruca vulgaris, impetigo and skin infestations are among those topics discussed."} {"id": "PMID:155245", "title": "Effect of ischemia on contractile and histochemical properties of the rat soleus muscle.", "content": "Ligature and section of the abdominal aorta results in only minor and temporary functional and metabolic changes in the slow soleus muscle of the rat. A very small decrease in maximal tetanic tension corresponds to a few scattered areas of damaged and necrotic muscle fibres, in which decreased succinic dehydrogenase and loss of phosphorylase activity was observed. A new experimental approach, i.e. ligature and section of the abdominal aorta combined with terminal devascularisation, preserving intact tendons and innervation of the muscle causes maximal muscle ischemia, followed by an almost complete loss of tetanic tension output, marked shortening of contraction time and profound morphological and histochemical changes. The decrease in succinic dehydrogenase and ATPase activities and loss of phosphorylase activity occur in the majority of degenerating muscle fibres except for a thin rim of peripheral fibres during the first 4 days. Subsequently, the contractile properties recover gradually and enzyme activities reappear in the regenerating muscle fibres simultaneously with new revascularisation. Thirty days after the operation all the parameters observed returned to control values.", "contents": "Effect of ischemia on contractile and histochemical properties of the rat soleus muscle. Ligature and section of the abdominal aorta results in only minor and temporary functional and metabolic changes in the slow soleus muscle of the rat. A very small decrease in maximal tetanic tension corresponds to a few scattered areas of damaged and necrotic muscle fibres, in which decreased succinic dehydrogenase and loss of phosphorylase activity was observed. A new experimental approach, i.e. ligature and section of the abdominal aorta combined with terminal devascularisation, preserving intact tendons and innervation of the muscle causes maximal muscle ischemia, followed by an almost complete loss of tetanic tension output, marked shortening of contraction time and profound morphological and histochemical changes. The decrease in succinic dehydrogenase and ATPase activities and loss of phosphorylase activity occur in the majority of degenerating muscle fibres except for a thin rim of peripheral fibres during the first 4 days. Subsequently, the contractile properties recover gradually and enzyme activities reappear in the regenerating muscle fibres simultaneously with new revascularisation. Thirty days after the operation all the parameters observed returned to control values."} {"id": "PMID:155253", "title": "Sixty latissimus dorsi flaps.", "content": "In clinical experiences with 60 cases, we have found the latissimus dorsi to be a reliable and versatile flap. We describe its use for a functional muscle transfer (in restoration of elbow flexion and repair of abdominal wall defects), for arm and shoulder coverage, for breast reconstruction, and as a free flap.", "contents": "Sixty latissimus dorsi flaps. In clinical experiences with 60 cases, we have found the latissimus dorsi to be a reliable and versatile flap. We describe its use for a functional muscle transfer (in restoration of elbow flexion and repair of abdominal wall defects), for arm and shoulder coverage, for breast reconstruction, and as a free flap."} {"id": "PMID:155280", "title": "Effects of sodium pentobarbital on rat heart sarcolemma.", "content": "The effects of sodium pentobarbital on ATPase, Ca2+ binding and adenylate cyclase activities of the rat heart sarcolemmal preparations were investigated. The Na+ - K+ ATPase activity was diminished by pentobarbital in concentrations as low as 0.3 mM. Mg2+ ATPase, Ca2+ ATPase and adenylate cyclase activities were also depressed but required 10 to 15 mM of this agent. Pentobarbital in concentrations of 10 mM, however, caused an increase in sarcolemmal Ca2+ binding. Mitochondrial and microsomal ATPase activities were decreased by 1 and 5 mM concentrations of pentobarbital respectively, while myofibrillar ATPase activity was unaltered even at a concentration of 20 mM. These data suggest that cardiodepressant effects of high doses of pentobarbital may partly be explained on the basis of its actions on heart sarcolemma.", "contents": "Effects of sodium pentobarbital on rat heart sarcolemma. The effects of sodium pentobarbital on ATPase, Ca2+ binding and adenylate cyclase activities of the rat heart sarcolemmal preparations were investigated. The Na+ - K+ ATPase activity was diminished by pentobarbital in concentrations as low as 0.3 mM. Mg2+ ATPase, Ca2+ ATPase and adenylate cyclase activities were also depressed but required 10 to 15 mM of this agent. Pentobarbital in concentrations of 10 mM, however, caused an increase in sarcolemmal Ca2+ binding. Mitochondrial and microsomal ATPase activities were decreased by 1 and 5 mM concentrations of pentobarbital respectively, while myofibrillar ATPase activity was unaltered even at a concentration of 20 mM. These data suggest that cardiodepressant effects of high doses of pentobarbital may partly be explained on the basis of its actions on heart sarcolemma."} {"id": "PMID:155285", "title": "Work and disability at the age of 30 years. A sociomedical study of a birth-cohort from Bergen. IV. Economic activity, occupation, and earned income.", "content": "On the basis of interviews and data collected from various files and registers, the present study will analyse the work situation at the age of 30 years related to the type of school attended at age 14 years. The study is based on a cohort of 1,570 persons, all live births in the year 1940 of mothers then residing in Bergen. A sample was taken after stratification of the cohort according to type of school attended at age 14 years. This sample was supplemented with persons who had attended Special Schools for the educable mentally retarded (EMR) and with persons who had received care from the national services for the mentally retarded (SMR). The final sample consisted of 262 persons. An association is found between economic activity, occupation, and earned income at the age of 30 years and type of school attended at age 14 years. Former pupils of Special Schools for the educable mentally retarded clearly belong to a marginal group, as regards \"self-support\". Former pupils of Elementary School classes for slow learners are also a high-risk group concerning the development of work-insufficiency.", "contents": "Work and disability at the age of 30 years. A sociomedical study of a birth-cohort from Bergen. IV. Economic activity, occupation, and earned income. On the basis of interviews and data collected from various files and registers, the present study will analyse the work situation at the age of 30 years related to the type of school attended at age 14 years. The study is based on a cohort of 1,570 persons, all live births in the year 1940 of mothers then residing in Bergen. A sample was taken after stratification of the cohort according to type of school attended at age 14 years. This sample was supplemented with persons who had attended Special Schools for the educable mentally retarded (EMR) and with persons who had received care from the national services for the mentally retarded (SMR). The final sample consisted of 262 persons. An association is found between economic activity, occupation, and earned income at the age of 30 years and type of school attended at age 14 years. Former pupils of Special Schools for the educable mentally retarded clearly belong to a marginal group, as regards \"self-support\". Former pupils of Elementary School classes for slow learners are also a high-risk group concerning the development of work-insufficiency."} {"id": "PMID:155286", "title": "Pharmacology and toxicology of Atrovent.", "content": "The anticholinergic drug ipratropium bromide (Atrovent) can be described as having pharmacologically a high degree of activity and a certain bronchoselectivity when administered intravenously. Inhalation studies, however, indicate that this is the most suitable route of administration. Inhalation provides with small doses the most effective concentration locally at the smooth muscle of the airways without producing anticholinergic side effects due to absorption from the airways or from the gastrointestinal tract. In certain experimental models of allergic asthma, ipratropium bromide was shown to be capable of influencing favourably bronchoconstriction and mediator release. Extensive toxicological examinations revealed with high doses all typical symptoms of overdosing an anticholinergic drug, like mydriasis, dryness of the mucosae and meteorism with coprostasis. Acute and long term inhalation studies gave no evidence for a functional and morphological impairment of the lungs and airways.", "contents": "Pharmacology and toxicology of Atrovent. The anticholinergic drug ipratropium bromide (Atrovent) can be described as having pharmacologically a high degree of activity and a certain bronchoselectivity when administered intravenously. Inhalation studies, however, indicate that this is the most suitable route of administration. Inhalation provides with small doses the most effective concentration locally at the smooth muscle of the airways without producing anticholinergic side effects due to absorption from the airways or from the gastrointestinal tract. In certain experimental models of allergic asthma, ipratropium bromide was shown to be capable of influencing favourably bronchoconstriction and mediator release. Extensive toxicological examinations revealed with high doses all typical symptoms of overdosing an anticholinergic drug, like mydriasis, dryness of the mucosae and meteorism with coprostasis. Acute and long term inhalation studies gave no evidence for a functional and morphological impairment of the lungs and airways."} {"id": "PMID:155294", "title": "A double blind cross-over study of maximal expiratory flows and arterial blood gas tensions in normals, asthmatics and bronchitics after salbutamol and ipratropin.", "content": "8 normals, 8 asthmatics and 8 bronchitics inhaled comparable doses of ipratropin and salbutamol. Five different flow-volume parameters were measured before and at intervals from 3 to 360 minutes after inhalation, on a total number of 2880 maximal effort expiratory flow-volume curves. Arterial blood gas tensions were measured before and 60 minutes after inhalation. In all parameters a significant larger effect (p less than 0.05) of ipratropin was found in normals, but in different time intervals. The parameter FEV1 and MEF at 50% of FVC showed the largest effect of salbutamol during the interval from 3 to 60 minutes in the asthma patients. None of the parameters showed significant difference in drug effects in the bronchitis patients. The findings suggested a more peripheral action of ipratropin than of salbutamol in the normals. No significant change in gas tensions were found after inhalation in any of the three groups.", "contents": "A double blind cross-over study of maximal expiratory flows and arterial blood gas tensions in normals, asthmatics and bronchitics after salbutamol and ipratropin. 8 normals, 8 asthmatics and 8 bronchitics inhaled comparable doses of ipratropin and salbutamol. Five different flow-volume parameters were measured before and at intervals from 3 to 360 minutes after inhalation, on a total number of 2880 maximal effort expiratory flow-volume curves. Arterial blood gas tensions were measured before and 60 minutes after inhalation. In all parameters a significant larger effect (p less than 0.05) of ipratropin was found in normals, but in different time intervals. The parameter FEV1 and MEF at 50% of FVC showed the largest effect of salbutamol during the interval from 3 to 60 minutes in the asthma patients. None of the parameters showed significant difference in drug effects in the bronchitis patients. The findings suggested a more peripheral action of ipratropin than of salbutamol in the normals. No significant change in gas tensions were found after inhalation in any of the three groups."} {"id": "PMID:155295", "title": "A comparative study of the bronchodilatating effects of ipratropium and terbutalin inhaled with Monaghan IPPB-M 515 by 19 patients with chronic obstructive airways disease.", "content": "The effect of ipratropium (Atrovent) 0.125 mg x 4 daily was compared to terbutalin (Bricanyl) 5 mg x 4 daily, given to 19 patients with chronic obstructive airways disease (15 with chronic bronchitis, 10 bronchial asthma, 7 pulmonary emphysema) as inhalation therapy with Monaghan IPPB-M 515, during 2 treatment periods of 3 days. The investigation was carried out as a controlled, double-blind, cross-over comparison. The effect of treatment was evaluated by measurement of PEFR, symptom scores, including the side-effects and the use of rimiterol MDI for the treatment of acute attacks. The PEFR values were all higher than the initial values (P less than 0.001) during the period of treatment (08.00-20,30 hrs). The highest values were recorded at 16.30 hrs, these were PEFR + 31.7% for the Atrovent period and PEFR + 28.0% for the Bricanyl period. No statistically significant difference was observed in the PEFR, symptom scores, side-effects and the use of rimiterol during the Atrovent and Bricanyl treatment periods. The authors suggest that Atrovent is a wellsuited alternative bronchodilatator, particularly for patients with tremor, muscle cramp, and \"inner restlessness\" following treatment with a beta 2-stimulator.", "contents": "A comparative study of the bronchodilatating effects of ipratropium and terbutalin inhaled with Monaghan IPPB-M 515 by 19 patients with chronic obstructive airways disease. The effect of ipratropium (Atrovent) 0.125 mg x 4 daily was compared to terbutalin (Bricanyl) 5 mg x 4 daily, given to 19 patients with chronic obstructive airways disease (15 with chronic bronchitis, 10 bronchial asthma, 7 pulmonary emphysema) as inhalation therapy with Monaghan IPPB-M 515, during 2 treatment periods of 3 days. The investigation was carried out as a controlled, double-blind, cross-over comparison. The effect of treatment was evaluated by measurement of PEFR, symptom scores, including the side-effects and the use of rimiterol MDI for the treatment of acute attacks. The PEFR values were all higher than the initial values (P less than 0.001) during the period of treatment (08.00-20,30 hrs). The highest values were recorded at 16.30 hrs, these were PEFR + 31.7% for the Atrovent period and PEFR + 28.0% for the Bricanyl period. No statistically significant difference was observed in the PEFR, symptom scores, side-effects and the use of rimiterol during the Atrovent and Bricanyl treatment periods. The authors suggest that Atrovent is a wellsuited alternative bronchodilatator, particularly for patients with tremor, muscle cramp, and \"inner restlessness\" following treatment with a beta 2-stimulator."} {"id": "PMID:155297", "title": "SCH 1000 in psychogenic asthma.", "content": "The effects of a beta 2-sympathomimetic (salbutamol or fenoterol) and the anticholinergic SCH 1000 administered both in combination and with placebo were compared in a double-blind random crossover design. Thirty-three patients with atopic, non-atopic and psychogenic asthma were studied. After inhalation of the sympathomimetic in combination with SCH 1000 or placebo the increase in FEV1 was significantly better for three hours (p less than 0.05) than after inhalation of SCH 1000 alone. There was no difference in the response to SCH 1000 in the atopic or non-atopic groups. However, in patients with a major psychogenic component to their asthma the FEV1 response to SCH 1000 was significantly better (p less than 0.05) than in other asthmatics from four to seven hours past inhalation. These findings suggest that SCH 1000 might be a valuable therapeutic agent in patients with psychogenic asthma.", "contents": "SCH 1000 in psychogenic asthma. The effects of a beta 2-sympathomimetic (salbutamol or fenoterol) and the anticholinergic SCH 1000 administered both in combination and with placebo were compared in a double-blind random crossover design. Thirty-three patients with atopic, non-atopic and psychogenic asthma were studied. After inhalation of the sympathomimetic in combination with SCH 1000 or placebo the increase in FEV1 was significantly better for three hours (p less than 0.05) than after inhalation of SCH 1000 alone. There was no difference in the response to SCH 1000 in the atopic or non-atopic groups. However, in patients with a major psychogenic component to their asthma the FEV1 response to SCH 1000 was significantly better (p less than 0.05) than in other asthmatics from four to seven hours past inhalation. These findings suggest that SCH 1000 might be a valuable therapeutic agent in patients with psychogenic asthma."} {"id": "PMID:155303", "title": "ASD in patients over 40 years of age.", "content": "To evaluate the benefits of operative treatment of congenital heart disease in older age groups, a clinical study on patients over 40 years of age with atrial septal defect was carried out. The series consisted of 125 consecutive patients operated on between 1966 and 1974. There were 8 cases with a primum, 12 cases with a sinus venosus type of secundum and 105 cases with a simple secundum defect. The operative mortality was 2 patients (1.6%). It was due to myocardial infarction in one case and high pulmonary vascular resistance in the other. On re-examination 3-6 months postoperatively, 107 patients were improved, 13 patients unchanged and 3 patients were worse than before operation. On re-evaluation after an average period of 6 years, 88 patients were still improved. 32 patients unchanged and 3 patients were worse compared with their pre-operative status. On the basis of the results and the previous reports on atrial septal defect without operation, the surgical correction of ASD even in older age groups can be recommended. The problem of deterioration of some patients, despite a good immediate postoperative result, is discussed.", "contents": "ASD in patients over 40 years of age. To evaluate the benefits of operative treatment of congenital heart disease in older age groups, a clinical study on patients over 40 years of age with atrial septal defect was carried out. The series consisted of 125 consecutive patients operated on between 1966 and 1974. There were 8 cases with a primum, 12 cases with a sinus venosus type of secundum and 105 cases with a simple secundum defect. The operative mortality was 2 patients (1.6%). It was due to myocardial infarction in one case and high pulmonary vascular resistance in the other. On re-examination 3-6 months postoperatively, 107 patients were improved, 13 patients unchanged and 3 patients were worse than before operation. On re-evaluation after an average period of 6 years, 88 patients were still improved. 32 patients unchanged and 3 patients were worse compared with their pre-operative status. On the basis of the results and the previous reports on atrial septal defect without operation, the surgical correction of ASD even in older age groups can be recommended. The problem of deterioration of some patients, despite a good immediate postoperative result, is discussed."} {"id": "PMID:155304", "title": "Clinical and haemodynamic observations after combined aortic and mitral valve replacement with the Bj\u00f6rk-Shiley tilting disc valve prosthesis. Early and late results in 25 patients.", "content": "Combined mitral and aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve (pyrolite) was performed in 25 unselected patients characterized by markedly impaired functional capacity, hypokinetic central circulation and cardiomegaly before operation. Surgery was performed during extracorporeal circulation with deep hypothermia. The mitral valve was replaced first in all cases. There were no intra-operative deaths, but 2 patients died while still in hospital (8.0%). One patient died 2 months postoperatively due to progressive heart failure. The remaining patients--with the exception of one who had died of cancer of the ovary--were re-examined in average 28.7 (18-40) months postoperatively. Most patients had improved symptomatically and were in functional classes I-II (N.Y.H.A.). The haemodynamic findings indicated restoration to normal resting values of cardiac output, pulmonary artery pressure and pulmonary vascular resistance, but with an increase in left ventricular end-diastolic pressure (LVEDP). The mean diastolic gradient across the mitral prosthesis varied from 0 to 11 mmHg, while simultaneous pressure recordings from the left ventricle and the aorta, with one exception, disclosed no systolic pressure gradients (peak) across the aortic valve. Postoperative arterial thrombo-embolic complications occurred in 2 patients, resulting in only minor neurological sequelae.", "contents": "Clinical and haemodynamic observations after combined aortic and mitral valve replacement with the Bj\u00f6rk-Shiley tilting disc valve prosthesis. Early and late results in 25 patients. Combined mitral and aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve (pyrolite) was performed in 25 unselected patients characterized by markedly impaired functional capacity, hypokinetic central circulation and cardiomegaly before operation. Surgery was performed during extracorporeal circulation with deep hypothermia. The mitral valve was replaced first in all cases. There were no intra-operative deaths, but 2 patients died while still in hospital (8.0%). One patient died 2 months postoperatively due to progressive heart failure. The remaining patients--with the exception of one who had died of cancer of the ovary--were re-examined in average 28.7 (18-40) months postoperatively. Most patients had improved symptomatically and were in functional classes I-II (N.Y.H.A.). The haemodynamic findings indicated restoration to normal resting values of cardiac output, pulmonary artery pressure and pulmonary vascular resistance, but with an increase in left ventricular end-diastolic pressure (LVEDP). The mean diastolic gradient across the mitral prosthesis varied from 0 to 11 mmHg, while simultaneous pressure recordings from the left ventricle and the aorta, with one exception, disclosed no systolic pressure gradients (peak) across the aortic valve. Postoperative arterial thrombo-embolic complications occurred in 2 patients, resulting in only minor neurological sequelae."} {"id": "PMID:155305", "title": "Successful replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries.", "content": "A 63-year-old man was operated upon with replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries. A composite graft with a 27 mm Bj\u00f6rk-Shiley tilting disc prosthesis was inserted with 3 continuous Prolene sutures in the aortic position. The coronary arteries were thereafter re-implanted in holes made in the graft. A 31 mm Bj\u00f6rk-Shiley valve was sutured in the mitral position with about 20 isolated mattress sutures of Ti-Cron. Selective myocardial hypothermia was instituted with Ringer's solution of 4 degrees C. The total perfusion time was 185 min compared with 240 and 275 min in two previously reported, similar cases. We consider that the use of cardioplegia, a composite graft and continuous sutures makes it possible to reduce the operation time in these complex cases. Our patient is in good condition 9 months postoperatively.", "contents": "Successful replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries. A 63-year-old man was operated upon with replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries. A composite graft with a 27 mm Bj\u00f6rk-Shiley tilting disc prosthesis was inserted with 3 continuous Prolene sutures in the aortic position. The coronary arteries were thereafter re-implanted in holes made in the graft. A 31 mm Bj\u00f6rk-Shiley valve was sutured in the mitral position with about 20 isolated mattress sutures of Ti-Cron. Selective myocardial hypothermia was instituted with Ringer's solution of 4 degrees C. The total perfusion time was 185 min compared with 240 and 275 min in two previously reported, similar cases. We consider that the use of cardioplegia, a composite graft and continuous sutures makes it possible to reduce the operation time in these complex cases. Our patient is in good condition 9 months postoperatively."} {"id": "PMID:155306", "title": "[Value of sonography in the diagnosis of obscure cholestasis].", "content": "A retrospective study has been conducted in 36 cholestatic patients to determine the diagnostic accuracy of ultrasonography in preliminary differentiation of obstructive from non-obstructive hepato-biliary disease. Due to the high rate of correct biliary duct caliber evaluation, ultrasonography has proved itself an excellent screening method in patients with cholestasis of uncertain origin. The choice of the subsequent more invasive diagnostic examinations (ERC, PTC, laparoscopy) depends on the ultrasonic findings.", "contents": "[Value of sonography in the diagnosis of obscure cholestasis]. A retrospective study has been conducted in 36 cholestatic patients to determine the diagnostic accuracy of ultrasonography in preliminary differentiation of obstructive from non-obstructive hepato-biliary disease. Due to the high rate of correct biliary duct caliber evaluation, ultrasonography has proved itself an excellent screening method in patients with cholestasis of uncertain origin. The choice of the subsequent more invasive diagnostic examinations (ERC, PTC, laparoscopy) depends on the ultrasonic findings."} {"id": "PMID:155308", "title": "Fibrinopeptide B and aggregation of fibrinogen.", "content": "Removal of fibrinopeptide B from human fibrinogen by reaction with the procoagulant enzyme from copperhead snake venom below 25 degrees C resulted in tight aggregation of the fibrinogen, which, in turn, progressively blocked a concomitant but sluggish release of fibrinopeptide A by the enzyme. When the clots obtained at less than 25 degrees C were warmed, they dissociated into soluble aggregates and monomers. Release of fibrinopeptide A then resumed, and a secondary coagulation followed. The aggregation induced by release of fibrinopeptide B itself involves a plasmin-susceptible segment located just distal to B in the B beta chain of fibrinogen, a segment previously shown to be of little importance in the aggregation induced by release of fibrinopeptide A.", "contents": "Fibrinopeptide B and aggregation of fibrinogen. Removal of fibrinopeptide B from human fibrinogen by reaction with the procoagulant enzyme from copperhead snake venom below 25 degrees C resulted in tight aggregation of the fibrinogen, which, in turn, progressively blocked a concomitant but sluggish release of fibrinopeptide A by the enzyme. When the clots obtained at less than 25 degrees C were warmed, they dissociated into soluble aggregates and monomers. Release of fibrinopeptide A then resumed, and a secondary coagulation followed. The aggregation induced by release of fibrinopeptide B itself involves a plasmin-susceptible segment located just distal to B in the B beta chain of fibrinogen, a segment previously shown to be of little importance in the aggregation induced by release of fibrinopeptide A."} {"id": "PMID:155309", "title": "Calcium transport across the plasma membrane: stimulation by calmodulin.", "content": "Active transport of calcium into inside-out vesicles of red blood cell membranes was stimulated equally by (i) the purified protein activator of calcium-activated, magnesium-dependent adenosinetriphosphatase isolated from red cell hemolyzates and (ii) calmodulin, a protein activator of cylic nucleotide phosphodiesterase isolated from bovine brain. The results provide further evidence for the identity of red blood cell activator and calmodulin and show that this cytoplasmic protein may participate in the regulation of plasma membrane calcium transport.", "contents": "Calcium transport across the plasma membrane: stimulation by calmodulin. Active transport of calcium into inside-out vesicles of red blood cell membranes was stimulated equally by (i) the purified protein activator of calcium-activated, magnesium-dependent adenosinetriphosphatase isolated from red cell hemolyzates and (ii) calmodulin, a protein activator of cylic nucleotide phosphodiesterase isolated from bovine brain. The results provide further evidence for the identity of red blood cell activator and calmodulin and show that this cytoplasmic protein may participate in the regulation of plasma membrane calcium transport."} {"id": "PMID:155310", "title": "Pneumococcal endocarditis in infants.", "content": "A case of pneumococcal endocarditis in an infant is reported together with a review of seven cases previously described in the literature. The prominent presenting symptoms of this usually fatal disease consisted of tachycardia, tachypnea, and cardiomegaly. A new murmur was heard in six of the eight patients. Fever was infrequent. Blood cultures were positive when done. The mitral valve was the site of infection in seven of the patients. In contrast to adult patients, pneumonia and meningitis are rarely encountered in children with pneumococcal endocarditis. The disease was fatal in all four patients before the penicillin era and in three of four patients who received penicillin.", "contents": "Pneumococcal endocarditis in infants. A case of pneumococcal endocarditis in an infant is reported together with a review of seven cases previously described in the literature. The prominent presenting symptoms of this usually fatal disease consisted of tachycardia, tachypnea, and cardiomegaly. A new murmur was heard in six of the eight patients. Fever was infrequent. Blood cultures were positive when done. The mitral valve was the site of infection in seven of the patients. In contrast to adult patients, pneumonia and meningitis are rarely encountered in children with pneumococcal endocarditis. The disease was fatal in all four patients before the penicillin era and in three of four patients who received penicillin."} {"id": "PMID:155312", "title": "An outbreak of plague in Hlegu, Burma in 1977.", "content": "An outbreak of plague occurred in Hlegu Town, Burma in February and March 1977. Altogether 14 bubonic plague cases, with 2 deaths were reported, mostly children under 15 years of age. Twice as many males as females were affected. A retrospective investigation showed that a rat fall took place in the last week of January. Only 9.5% of the rodents which died in the epizootic were found to be infected with Y. pestis; this apparent low infection rate probably resulted from the inclusion in the survey of some dead rats which died of other causes. 14.5% out of 48 trapped rodents were found to be serologically positive. The general flea and cheopis indices were rather high, perhaps because fleas were found to be partially resistant to DDT and also because spraying of insecticide did not effect fleas on the hosts. The cheopis index in Hlegu Town was 1.17, and less than 0.5 in Hlegu suburb (Yankin-Yat) where no epizootic was reported. An active case search revealed 76 suspected plague cases out of which 11 were found to have bubonic plague. A field trial showed that plague vaccination during the outbreak did not result in a rise of detectable antibodies in persons inoculated.", "contents": "An outbreak of plague in Hlegu, Burma in 1977. An outbreak of plague occurred in Hlegu Town, Burma in February and March 1977. Altogether 14 bubonic plague cases, with 2 deaths were reported, mostly children under 15 years of age. Twice as many males as females were affected. A retrospective investigation showed that a rat fall took place in the last week of January. Only 9.5% of the rodents which died in the epizootic were found to be infected with Y. pestis; this apparent low infection rate probably resulted from the inclusion in the survey of some dead rats which died of other causes. 14.5% out of 48 trapped rodents were found to be serologically positive. The general flea and cheopis indices were rather high, perhaps because fleas were found to be partially resistant to DDT and also because spraying of insecticide did not effect fleas on the hosts. The cheopis index in Hlegu Town was 1.17, and less than 0.5 in Hlegu suburb (Yankin-Yat) where no epizootic was reported. An active case search revealed 76 suspected plague cases out of which 11 were found to have bubonic plague. A field trial showed that plague vaccination during the outbreak did not result in a rise of detectable antibodies in persons inoculated."} {"id": "PMID:155313", "title": "Another case of human gnathostomiasis in Indonesia.", "content": "A male Gnathostoma spinigerum was removed from the abdominal wall of a 29-year-old woman, who was in the habit of eating \"naniura\", a dish containing raw carp (Cyprinus carpio). After the removal of the worm she still had pain in her chest and noticed intermittent swelling of her right lower arm. Probably the patient still had one or more Gnathostoma worms migrating in her body.", "contents": "Another case of human gnathostomiasis in Indonesia. A male Gnathostoma spinigerum was removed from the abdominal wall of a 29-year-old woman, who was in the habit of eating \"naniura\", a dish containing raw carp (Cyprinus carpio). After the removal of the worm she still had pain in her chest and noticed intermittent swelling of her right lower arm. Probably the patient still had one or more Gnathostoma worms migrating in her body."} {"id": "PMID:155321", "title": "Inferior mesenteric artery aneurysm: case report and discussion.", "content": "Although visceral artery aneurysms are uncommon, an isolated inferior mesenteric artery aneurysm is reported. A 55-year-old man underwent aortofemoral reconstruction with resection of the aneurysm and replantation of the artery into the Dacron graft. This unusual entity is discussed.", "contents": "Inferior mesenteric artery aneurysm: case report and discussion. Although visceral artery aneurysms are uncommon, an isolated inferior mesenteric artery aneurysm is reported. A 55-year-old man underwent aortofemoral reconstruction with resection of the aneurysm and replantation of the artery into the Dacron graft. This unusual entity is discussed."} {"id": "PMID:155322", "title": "Chemotherapy of gastric and pancreatic carcinoma: a controlled evaluation of combinations of 5-fluorouracil with nitrosoureas and \"lactones\".", "content": "By random assignment a total of 176 eligible patients with advanced nonmeasurable pancreatic carcinoma were treated with 5-fluorouracil (5-FU) either alone or in combination with a nitrosourea (streptozotocin), in combination with a \"lactone\" (spironolactone), or in combination with both. By random assignment a total of 179 patients with advanced nonmeasurable gastric carcinoma were treated with 5-FU either alone or in combination with a nitrosourea (methyl CCNU), in combination with a lactone (testolactone), or in combination with both. The median survival period for all pancreatic carcinoma patients was 17 weeks, and for all gastric carcinoma patients 30 weeks. The addition of the nitrosoureas or the lactones or a combination of both produced no improvement in length of patient survival for either primary carcinoma when compared to treatment with 5-FU alone.", "contents": "Chemotherapy of gastric and pancreatic carcinoma: a controlled evaluation of combinations of 5-fluorouracil with nitrosoureas and \"lactones\". By random assignment a total of 176 eligible patients with advanced nonmeasurable pancreatic carcinoma were treated with 5-fluorouracil (5-FU) either alone or in combination with a nitrosourea (streptozotocin), in combination with a \"lactone\" (spironolactone), or in combination with both. By random assignment a total of 179 patients with advanced nonmeasurable gastric carcinoma were treated with 5-FU either alone or in combination with a nitrosourea (methyl CCNU), in combination with a lactone (testolactone), or in combination with both. The median survival period for all pancreatic carcinoma patients was 17 weeks, and for all gastric carcinoma patients 30 weeks. The addition of the nitrosoureas or the lactones or a combination of both produced no improvement in length of patient survival for either primary carcinoma when compared to treatment with 5-FU alone."} {"id": "PMID:155319", "title": "The MMPI as a predictor of outcome in low-back surgery.", "content": "Between 1965 and 1975, 103 low-back patients were rated preoperatively for general level of functioning, and each completed a Minnesota Multiphasic Personality Inventory (MMPI) test. Following surgery, patients were rated in terms of treatment effectiveness at 6 months and 1 year. The MMPI hypochondriasis and hysteria scales were moderately related to surgical success, as were the severity of initial restriction in the level of functioning and the number of operations performed during the study. However, the MMPI profiles were strikingly similar for all patients. Factors which were not predictive of surgical outcome included age, sex, duration of symptoms, number of back surgeries prior to entering this clinic, and the degree of pathologic condition discovered at operation. The failure to find a potent prediction scheme confirms that MMPI information must be used with considerable caution in treatment planning and only as an adjunct to other clinical and psychological data.", "contents": "The MMPI as a predictor of outcome in low-back surgery. Between 1965 and 1975, 103 low-back patients were rated preoperatively for general level of functioning, and each completed a Minnesota Multiphasic Personality Inventory (MMPI) test. Following surgery, patients were rated in terms of treatment effectiveness at 6 months and 1 year. The MMPI hypochondriasis and hysteria scales were moderately related to surgical success, as were the severity of initial restriction in the level of functioning and the number of operations performed during the study. However, the MMPI profiles were strikingly similar for all patients. Factors which were not predictive of surgical outcome included age, sex, duration of symptoms, number of back surgeries prior to entering this clinic, and the degree of pathologic condition discovered at operation. The failure to find a potent prediction scheme confirms that MMPI information must be used with considerable caution in treatment planning and only as an adjunct to other clinical and psychological data."} {"id": "PMID:155320", "title": "Anterior spinal tenderness in low-back pain syndromes.", "content": "This paper describes the clinical sign of anterior tenderness of the lumbar spine in patients with low-back pain, the method of examination recommended, and the possible significance of such tenderness. The precise mechanism of this tenderness is not clear because of a lack of knowledge of the neuroanatomy of the anterior part of the spine. Anterior palpation of the lumbar spine should be considered part of a full routine examination in patients with low-back pain. Long-term follow-up and observations will be required before the full significance of this sign is revealed.", "contents": "Anterior spinal tenderness in low-back pain syndromes. This paper describes the clinical sign of anterior tenderness of the lumbar spine in patients with low-back pain, the method of examination recommended, and the possible significance of such tenderness. The precise mechanism of this tenderness is not clear because of a lack of knowledge of the neuroanatomy of the anterior part of the spine. Anterior palpation of the lumbar spine should be considered part of a full routine examination in patients with low-back pain. Long-term follow-up and observations will be required before the full significance of this sign is revealed."} {"id": "PMID:155326", "title": "The disability oriented rehabilitation unit--a major factor influencing stroke outcome.", "content": "Many investigators have analyzed the effectiveness of the cardiac care unit (as a model of a disability oriented, specially staffed, geographically isolated unit) in altering outcome following acute myocardial infarction. Little data are available, however, on the efficacy of caring for patients with stroke on specially staffed disability oriented units. Of 667 patients with stroke recently discharged from the Burke Rehabilitation Center, 589 were admitted to the stroke unit (SU group) and 78 were admitted to other units (NSU group). Statistical analysis showed that the SU patients were significantly weaker, had longer onset-admission intervals, and exhibited more concurrent medical problems and neurologic deficits. There were no statistically significant intergroup differences in age, sex, and distribution of weakness. Both groups had similar treatment programs provided by staff who had rotated through the stroke unit. Ability to perform activities of daily living (dressing, feeding, hygiene, bowel and bladder routines) and length of hospitalization were similar for both groups. SU patients walked better and went home more frequently than NSU patients. These data indicate than even in a rehabilitation center specializing in treating functional disabilities, patients with stroke are more likely to improve if placed on a disability oriented unit than if they are admitted to mixed disability units which are scattered throughout the hospital.", "contents": "The disability oriented rehabilitation unit--a major factor influencing stroke outcome. Many investigators have analyzed the effectiveness of the cardiac care unit (as a model of a disability oriented, specially staffed, geographically isolated unit) in altering outcome following acute myocardial infarction. Little data are available, however, on the efficacy of caring for patients with stroke on specially staffed disability oriented units. Of 667 patients with stroke recently discharged from the Burke Rehabilitation Center, 589 were admitted to the stroke unit (SU group) and 78 were admitted to other units (NSU group). Statistical analysis showed that the SU patients were significantly weaker, had longer onset-admission intervals, and exhibited more concurrent medical problems and neurologic deficits. There were no statistically significant intergroup differences in age, sex, and distribution of weakness. Both groups had similar treatment programs provided by staff who had rotated through the stroke unit. Ability to perform activities of daily living (dressing, feeding, hygiene, bowel and bladder routines) and length of hospitalization were similar for both groups. SU patients walked better and went home more frequently than NSU patients. These data indicate than even in a rehabilitation center specializing in treating functional disabilities, patients with stroke are more likely to improve if placed on a disability oriented unit than if they are admitted to mixed disability units which are scattered throughout the hospital."} {"id": "PMID:155334", "title": "An enzymatic method permitting early determination of histocompatibility in mixed lymphocyte culture.", "content": "The standard mixed lymphocyte culture assay, which measures the incorporation of [3H]thymidine into DNA, usually requires 5 days. We describe a more rapid assay based on changes in the activity of ornithine decarboxylase. An increase in the activity of ornithine decarboxylase was observed in mixed lymphocyte cultures from genetically defined, major histocompatibility complex (MHC)-nonidentical miniature swine as early as 18 hr after plating. No increase was found in mixed cultures from inbred MHC-identical animals. Similar results were obtained with the enzyme S-adenosylmethionine decarboxylase with the increase in activity starting at about 32 hr. There was a good correlation between the ornithine decarboxylase values at 18 hr and the results of the [3H]thymidine incorporation assay on day 5. Preliminary experiments with human lymphocytes revealed similar results.", "contents": "An enzymatic method permitting early determination of histocompatibility in mixed lymphocyte culture. The standard mixed lymphocyte culture assay, which measures the incorporation of [3H]thymidine into DNA, usually requires 5 days. We describe a more rapid assay based on changes in the activity of ornithine decarboxylase. An increase in the activity of ornithine decarboxylase was observed in mixed lymphocyte cultures from genetically defined, major histocompatibility complex (MHC)-nonidentical miniature swine as early as 18 hr after plating. No increase was found in mixed cultures from inbred MHC-identical animals. Similar results were obtained with the enzyme S-adenosylmethionine decarboxylase with the increase in activity starting at about 32 hr. There was a good correlation between the ornithine decarboxylase values at 18 hr and the results of the [3H]thymidine incorporation assay on day 5. Preliminary experiments with human lymphocytes revealed similar results."} {"id": "PMID:155335", "title": "Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat.", "content": "The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulating capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude.", "contents": "Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat. The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulating capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude."} {"id": "PMID:155333", "title": "Sodium and potassium changes in blood bank stored human erythrocytes.", "content": "Storage of red cells for three weeks at 4 C under blood bank conditions resulted in a rise in intracellular Na+ and a fall in intracellular K+ with concomitant opposite changes in Na+ and K+ levels in the suspending plasma. A decline in red blood cell ATP during the storage period did not appear to be contributing to the changes. Increasing red blood cell ATP to levels 2 to 3 times normal did not prevent the cation changes from occurring. When assayed at 37 C in the presence of added Mg++, ouabain-sensitive membrane ATPase activity and kinetics of activation by Na+ were unaffected by the three week period of cold storage. However, when assayed at 4 C without added Mg++, simulating the conditions of storage, ATPase activity was negligible. Sodium and potassium did not change when red blood cells with normal ATP content were stored at 20 to 24 C even in the absence of added Mg++. Thus, a major cause for the development of cation changes in the red blood cell during blood bank storage in the temperature which inhibits membrane ATPase, allowing cations to leak unopposed into and out of the red blood cells.", "contents": "Sodium and potassium changes in blood bank stored human erythrocytes. Storage of red cells for three weeks at 4 C under blood bank conditions resulted in a rise in intracellular Na+ and a fall in intracellular K+ with concomitant opposite changes in Na+ and K+ levels in the suspending plasma. A decline in red blood cell ATP during the storage period did not appear to be contributing to the changes. Increasing red blood cell ATP to levels 2 to 3 times normal did not prevent the cation changes from occurring. When assayed at 37 C in the presence of added Mg++, ouabain-sensitive membrane ATPase activity and kinetics of activation by Na+ were unaffected by the three week period of cold storage. However, when assayed at 4 C without added Mg++, simulating the conditions of storage, ATPase activity was negligible. Sodium and potassium did not change when red blood cells with normal ATP content were stored at 20 to 24 C even in the absence of added Mg++. Thus, a major cause for the development of cation changes in the red blood cell during blood bank storage in the temperature which inhibits membrane ATPase, allowing cations to leak unopposed into and out of the red blood cells."} {"id": "PMID:155340", "title": "Efficacy of febantel in sheep experimentally infected with five species of gastrointestinal nematodes.", "content": "The anthelmintic activity of the guanidine derivative febantel was tested in a total of 76 experimentally infected lambs in two control tests. Doses of 5.0 and 7.5 mg per kg body-weight were administered orally against fourth and pre-adult fifth or adult stages of Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformis, B unostomum trigonocephalum and Oesophagostomum columbianum. The efficacy was between 98.5 and 100 per cent. The drug was well tolerated.", "contents": "Efficacy of febantel in sheep experimentally infected with five species of gastrointestinal nematodes. The anthelmintic activity of the guanidine derivative febantel was tested in a total of 76 experimentally infected lambs in two control tests. Doses of 5.0 and 7.5 mg per kg body-weight were administered orally against fourth and pre-adult fifth or adult stages of Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformis, B unostomum trigonocephalum and Oesophagostomum columbianum. The efficacy was between 98.5 and 100 per cent. The drug was well tolerated."} {"id": "PMID:155356", "title": "[Pathogenetic therapy of mastopathies in the prevention of breast cancer].", "content": "The breast cancer morbidity among the population of the city of Leningrad has been analysed. It was shown that there is a tendency to the increased number of breast cancer patients. In this respect attention is given to the prophylactic measures, accomplished in Leningrad City oncological dyspensary. As proved statistically, the pathogenetic therapy of mastopathy is a factor contributing to less risk of malignant transformation. For the statistical analysis the authors used the data of 132 breast cancer patients; previously operated upon for local fibroadenomatosis, and the data of 259 control patients. It was found that among the patients with fibroadenomatosis who subsequently developed cancer of the mammary gland, the proportion of untreated patients was 2.8 times as much as in the control group.", "contents": "[Pathogenetic therapy of mastopathies in the prevention of breast cancer]. The breast cancer morbidity among the population of the city of Leningrad has been analysed. It was shown that there is a tendency to the increased number of breast cancer patients. In this respect attention is given to the prophylactic measures, accomplished in Leningrad City oncological dyspensary. As proved statistically, the pathogenetic therapy of mastopathy is a factor contributing to less risk of malignant transformation. For the statistical analysis the authors used the data of 132 breast cancer patients; previously operated upon for local fibroadenomatosis, and the data of 259 control patients. It was found that among the patients with fibroadenomatosis who subsequently developed cancer of the mammary gland, the proportion of untreated patients was 2.8 times as much as in the control group."} {"id": "PMID:155360", "title": "[Late manifestation of a burn of intestine caused by laparoscopic tubal sterilization (author's transl)].", "content": "12 days after laparoscopic tubal sterilization by unipolar high-frequency current the clinical picture of an acute abdomen developed as sequel of a burn of small intestine followed by perforation and peritonitis. Symptomatology and therapy are discussed.", "contents": "[Late manifestation of a burn of intestine caused by laparoscopic tubal sterilization (author's transl)]. 12 days after laparoscopic tubal sterilization by unipolar high-frequency current the clinical picture of an acute abdomen developed as sequel of a burn of small intestine followed by perforation and peritonitis. Symptomatology and therapy are discussed."} {"id": "PMID:155361", "title": "[Metaphylaxis, protection of the disabled and assessment of impairments by extra-pulmonary tuberculosis (author's transl)].", "content": "Problems of metaphylaxis, the care of disabled and impairments by extrapulmonary tuberculosis need special attention in the care of patients by the Policlinical Department for lung-diseases and tuberculosis. In order to realise and to approve the specific control recommendations for the follow-up and examination of impairments are given by which the work of care-services and the execution of control-measure on the appointed day in their daily activities is facilitated. Bacteriological control by culture and special X-ray-examination must be performed with superior rank. The assessment of impairments and the protection of the disabled correspond to the opinion of experts in these special fields where extrapulmonary tuberculosis has any importance.", "contents": "[Metaphylaxis, protection of the disabled and assessment of impairments by extra-pulmonary tuberculosis (author's transl)]. Problems of metaphylaxis, the care of disabled and impairments by extrapulmonary tuberculosis need special attention in the care of patients by the Policlinical Department for lung-diseases and tuberculosis. In order to realise and to approve the specific control recommendations for the follow-up and examination of impairments are given by which the work of care-services and the execution of control-measure on the appointed day in their daily activities is facilitated. Bacteriological control by culture and special X-ray-examination must be performed with superior rank. The assessment of impairments and the protection of the disabled correspond to the opinion of experts in these special fields where extrapulmonary tuberculosis has any importance."} {"id": "PMID:155363", "title": "Mucopolysaccharides in bronchial secretion of children.", "content": "The diseases of respiratory system are nowadays one of the important medical, economical and social problems of modern civilization. A common symptom of these diseases regardless of their etiology, character, klinical manifestation and morphological findings is hypersecretion of bronchial sputum. Tracheobronchial mucus is produced by mucous bronchial glands and goblet cells. This mucus represents at physiological condition about 5 micrometer thick cover on mucous of nasopharynx, larynx, trachea, bronchi up to terminal bronchioles. Protective function of mucus cover resposes in mechanical and humoral barrier and also in removing the inhaled particles and their transport to the upper part of the respiratory system. In spite of the fact, that bronchial secretion has an important role in protective mechanism and in thermal and water exchange of respiratory tract, this secretion is not sufficiently scrutinized mainly of children yet.", "contents": "Mucopolysaccharides in bronchial secretion of children. The diseases of respiratory system are nowadays one of the important medical, economical and social problems of modern civilization. A common symptom of these diseases regardless of their etiology, character, klinical manifestation and morphological findings is hypersecretion of bronchial sputum. Tracheobronchial mucus is produced by mucous bronchial glands and goblet cells. This mucus represents at physiological condition about 5 micrometer thick cover on mucous of nasopharynx, larynx, trachea, bronchi up to terminal bronchioles. Protective function of mucus cover resposes in mechanical and humoral barrier and also in removing the inhaled particles and their transport to the upper part of the respiratory system. In spite of the fact, that bronchial secretion has an important role in protective mechanism and in thermal and water exchange of respiratory tract, this secretion is not sufficiently scrutinized mainly of children yet."} {"id": "PMID:155358", "title": "[Isolation of influenza virus with the antigenic formula Hav4 Nav2 and Hav5 Nav2 during epizootic infection among sea gulls in the Astrakhan district in the summer of 1976].", "content": "Virological examinations of nesting colonies of Laridae birds in the avandelta of the Volga, Astrakhan region, during an epizootic in July, 1976, yielded 5 strains of influenza virus: 3 from Sterna albifrons, 1 from S. hirundo and 1 from Larus genei, identical with A/Sterna hirundo/S. Africa/61 (Hav5 Nav2) virus. At the same period two strains were isolated from Larus genei showing a previously unknown composition of the surface antigens: Hav4 Nav2. All the strains were isolated only from cloacal washings.", "contents": "[Isolation of influenza virus with the antigenic formula Hav4 Nav2 and Hav5 Nav2 during epizootic infection among sea gulls in the Astrakhan district in the summer of 1976]. Virological examinations of nesting colonies of Laridae birds in the avandelta of the Volga, Astrakhan region, during an epizootic in July, 1976, yielded 5 strains of influenza virus: 3 from Sterna albifrons, 1 from S. hirundo and 1 from Larus genei, identical with A/Sterna hirundo/S. Africa/61 (Hav5 Nav2) virus. At the same period two strains were isolated from Larus genei showing a previously unknown composition of the surface antigens: Hav4 Nav2. All the strains were isolated only from cloacal washings."} {"id": "PMID:155357", "title": "[Hygienic evaluation of the nutrition of the population in relation to endemic urolithiasis in the Chuvash ASSR].", "content": "By looking into the alimentary habits of the rural population residing in the urolithiasis endemic and non-endemic districts of the Chuvash ASSR the author ascertained definite differences in the content of calcium, silicon, strontium, manganese and cadmium in food rations of representative population groups under comparison. In the authors' opinion an elevated content of calcium, strontium, silicon, manganese and cadmium in food rations in inhabitants of the urolithiasis endemic districts is responsible for the urolithias endemy in the south-western areas of the republic.", "contents": "[Hygienic evaluation of the nutrition of the population in relation to endemic urolithiasis in the Chuvash ASSR]. By looking into the alimentary habits of the rural population residing in the urolithiasis endemic and non-endemic districts of the Chuvash ASSR the author ascertained definite differences in the content of calcium, silicon, strontium, manganese and cadmium in food rations of representative population groups under comparison. In the authors' opinion an elevated content of calcium, strontium, silicon, manganese and cadmium in food rations in inhabitants of the urolithiasis endemic districts is responsible for the urolithias endemy in the south-western areas of the republic."} {"id": "PMID:155359", "title": "[Various problems of epidemiology of viral hepatitis].", "content": "Because a rise in incidence of virus hepatitis observed in some years and showing an epidemic nature begins in one year and continues in the first quarter of the following year, it is recommended to register the incidence not from January to December, but from July to June of the next year in studies of some regularities of the epidemic process. Also, since in Baku a rise in incidence begins in July, it is suggested that planned gamma globulin prophylaxis be carried out not in September, but in early July. It has been established that children under 14 have virus hepatitis type A 10--24.4 times as frequently as adults.", "contents": "[Various problems of epidemiology of viral hepatitis]. Because a rise in incidence of virus hepatitis observed in some years and showing an epidemic nature begins in one year and continues in the first quarter of the following year, it is recommended to register the incidence not from January to December, but from July to June of the next year in studies of some regularities of the epidemic process. Also, since in Baku a rise in incidence begins in July, it is suggested that planned gamma globulin prophylaxis be carried out not in September, but in early July. It has been established that children under 14 have virus hepatitis type A 10--24.4 times as frequently as adults."} {"id": "PMID:155378", "title": "A comparison of the lytic activity of poultry, human, and bovine phages with staphylococci of different origin.", "content": "The total of 625 staphylococcal strains of different origin were typed with 22 Shimizu's poultry phages. For comparison all these strains were also investigated with the 24 phages of the international basic set for typing human staphylococci and with the 12 phages for typing bovine staphylococci. Of the 325 Staphylococcus aureus strains 50 from humans belonged to A biotype, 100 from chickens to B biotype and further 175 animal strains (of swine, rabbit, bovine, sheep, and hare provenance) to B, C, and D biotypes. Lytic activity of the poultry phages used at routine test dilution showed marked specificity related to the chicken strains were lysed. They were predominantly susceptible to phages CH4, CH14, CH15, CHA1, CHA2, CHA3, and CHA4. Most of the strains thus belonged to phage group I (74.0%), the others to phage groups II and III (18.0% and 2.0%). The examined strains of the other origins were either typable only sporadically (human in 4.0%, rabbit and bovine in 6.7%) or completely resistant. When the poultry phages were used at 100 x RTD the number of typable strains increased more significantly only in swine, rabbit, and bovine strains (23.3%, 60.0%, and 56.6%). On the contrary, human and bovine phages lysed chicken strains merely in 14.0% and 1.0% at RTD and in 20.0% and 3.0% at 100 x RTD respectively. All the 200 Staphylococcus intermedius and 100 Staphylococcus hyicus strains were resistant to the used 58 phages at RTD. When examined at 100 x RTD three Staph. hyicus strains were typable with the group IV phage CH11 from the poultry set, only.", "contents": "A comparison of the lytic activity of poultry, human, and bovine phages with staphylococci of different origin. The total of 625 staphylococcal strains of different origin were typed with 22 Shimizu's poultry phages. For comparison all these strains were also investigated with the 24 phages of the international basic set for typing human staphylococci and with the 12 phages for typing bovine staphylococci. Of the 325 Staphylococcus aureus strains 50 from humans belonged to A biotype, 100 from chickens to B biotype and further 175 animal strains (of swine, rabbit, bovine, sheep, and hare provenance) to B, C, and D biotypes. Lytic activity of the poultry phages used at routine test dilution showed marked specificity related to the chicken strains were lysed. They were predominantly susceptible to phages CH4, CH14, CH15, CHA1, CHA2, CHA3, and CHA4. Most of the strains thus belonged to phage group I (74.0%), the others to phage groups II and III (18.0% and 2.0%). The examined strains of the other origins were either typable only sporadically (human in 4.0%, rabbit and bovine in 6.7%) or completely resistant. When the poultry phages were used at 100 x RTD the number of typable strains increased more significantly only in swine, rabbit, and bovine strains (23.3%, 60.0%, and 56.6%). On the contrary, human and bovine phages lysed chicken strains merely in 14.0% and 1.0% at RTD and in 20.0% and 3.0% at 100 x RTD respectively. All the 200 Staphylococcus intermedius and 100 Staphylococcus hyicus strains were resistant to the used 58 phages at RTD. When examined at 100 x RTD three Staph. hyicus strains were typable with the group IV phage CH11 from the poultry set, only."} {"id": "PMID:155381", "title": "[Serovars of NAG vibrios isolated from the water of open reservoirs].", "content": "Composition of serological types of NAG-vibrios isolated from the river water contaminated by effluents was found to be more varied than in uncontaminated water body. Vibrios of serological types 6, 8, 39, 41, 50, 53, 55 revealed frequently and in great amounts apparently inhabit the mentioned water bodies for prolonged periods.", "contents": "[Serovars of NAG vibrios isolated from the water of open reservoirs]. Composition of serological types of NAG-vibrios isolated from the river water contaminated by effluents was found to be more varied than in uncontaminated water body. Vibrios of serological types 6, 8, 39, 41, 50, 53, 55 revealed frequently and in great amounts apparently inhabit the mentioned water bodies for prolonged periods."} {"id": "PMID:155382", "title": "Dynamic properties of in vitro enzyme systems containing phosphofructokinase.", "content": "The dynamic properties of a series of in vitro reaction systems with increasing complexity and containing phosphofructokinase as central enzyme have been investigated. An experimental strategy and a principal mathematical treatment was elaborated to search for the minimum requirements with respect to the enzyme composition of a reaction system for generating limit cycle behaviour. As a criterion, such models have been developed which permit experimental realization by application of a specially designed flow-through equipment. In addition to phosphofructokinase, the following enzymes have been stepwise included into the reaction systems composing the Models 1 through 6: pyruvate kinase, adenylate kinase, hexokinase, and glucose 6-phosphate isomerase. It turned out that only a minimum dynamic system containing phosphofructokinase and pyruvate kinase as well as excesses of adenylate kinase and glucose 6-phosphate isomerase for maintaining equilibrium conditions between the respective reacting species, acquires the property of limit cycle behaviour and, hence, to generate sustained self-oscillations. The approach permits to compute the region of the experimentally variable parameters (influx rates of fructose 6-phosphate and ATP, maximum rate of pyruvate kianse) for which self-oscillatory behaviour can be predicted.", "contents": "Dynamic properties of in vitro enzyme systems containing phosphofructokinase. The dynamic properties of a series of in vitro reaction systems with increasing complexity and containing phosphofructokinase as central enzyme have been investigated. An experimental strategy and a principal mathematical treatment was elaborated to search for the minimum requirements with respect to the enzyme composition of a reaction system for generating limit cycle behaviour. As a criterion, such models have been developed which permit experimental realization by application of a specially designed flow-through equipment. In addition to phosphofructokinase, the following enzymes have been stepwise included into the reaction systems composing the Models 1 through 6: pyruvate kinase, adenylate kinase, hexokinase, and glucose 6-phosphate isomerase. It turned out that only a minimum dynamic system containing phosphofructokinase and pyruvate kinase as well as excesses of adenylate kinase and glucose 6-phosphate isomerase for maintaining equilibrium conditions between the respective reacting species, acquires the property of limit cycle behaviour and, hence, to generate sustained self-oscillations. The approach permits to compute the region of the experimentally variable parameters (influx rates of fructose 6-phosphate and ATP, maximum rate of pyruvate kianse) for which self-oscillatory behaviour can be predicted."} {"id": "PMID:155383", "title": "An indirect method to examine forces affecting Courvoisier's oblique gall-bladder incision.", "content": "The aim of this study is to establish a method by which the maximum forces attacking Courvoisier's oblique gall-bladder incision can be evaluated. Nine well-informed patients served as subjects. Four investigations were made: pre-, per-, and two postoperative. The pre- and postoperative maximum isometric muscle strength in pulling forward were measured with a dynamometer. Simultaneously the IEMG was obtained. A muscle tensiometer was used for registration of the peroperative muscle pull of the right abdominal rectus muscle, and IEMG obtained simultaneously. The IEMG makes a calculation of the pre- and postoperative rectus muscle pull possible. The study seems to indicate that the most realistic estimation of the forces attacking the wound in the early postoperative phase is a preoperative measurement of the maximum force in pulling forward (attempted trunk bending). If ruptures in the wound occur during the extubation, ruptures would very likely also occur in the early postoperative phase. Eight weeks after the operation the right rectus muscle has regained its preoperative strength.", "contents": "An indirect method to examine forces affecting Courvoisier's oblique gall-bladder incision. The aim of this study is to establish a method by which the maximum forces attacking Courvoisier's oblique gall-bladder incision can be evaluated. Nine well-informed patients served as subjects. Four investigations were made: pre-, per-, and two postoperative. The pre- and postoperative maximum isometric muscle strength in pulling forward were measured with a dynamometer. Simultaneously the IEMG was obtained. A muscle tensiometer was used for registration of the peroperative muscle pull of the right abdominal rectus muscle, and IEMG obtained simultaneously. The IEMG makes a calculation of the pre- and postoperative rectus muscle pull possible. The study seems to indicate that the most realistic estimation of the forces attacking the wound in the early postoperative phase is a preoperative measurement of the maximum force in pulling forward (attempted trunk bending). If ruptures in the wound occur during the extubation, ruptures would very likely also occur in the early postoperative phase. Eight weeks after the operation the right rectus muscle has regained its preoperative strength."} {"id": "PMID:155385", "title": "Biologically active luteinizing hormone (LH) in plasma. III. Validation of the in vitro bioassay when applied to male plasma and the possible role of steroidal precursors.", "content": "An in vitro bioassay method for measuring LH activity was applied to male plasma. This method is based on the specific testosterone response to LH activity by interstitial cells from mouse testes. In contrast to assays conducted on female plasma, non-parallel response lines were obtained between serial dilutions of untreated male plasma and the International Reference Preparation for Human Pituitary Gonadotrophins FSH and LH/ICSH) for bioassay (code no. 69/104). In an attempt to eliminate this source of error, which would invalidate the assays, plasma was subjected to either ether extraction or charcoal adsorption prior to assay. While ether extraction was ineffective, charcoal treatment eliminated the source of non-parallelism. Evidence is presented indicating that the inclusion of a charcoal pre-treatment step provides an assay method for LH which fulfils the recognized criteria of reliability when applied to male plasma. An investigation of the likely causes of non-parallelism was undertaken by incubating mouse interstitial cells with various steroids and steroid sulphates at concentrations likely to be present in plasma. While most of the presumed precursors of testosterone were converted to testosterone, steroid sulphates (dehydroepiandrosterone sulphate and pregnenolone sulphate) at high concentrations as present in male plasma were the most active compounds in forming testosterone. However, the amount of testosterone produced from these precursors under controlled conditions was insufficient to account entirely for the deviation from parallelism observed with male plasma. Hence, the non-parallelism observed with untreated plasma samples cannot be entirely explained by the presence of steroidal testosterone precursors in male plasma.", "contents": "Biologically active luteinizing hormone (LH) in plasma. III. Validation of the in vitro bioassay when applied to male plasma and the possible role of steroidal precursors. An in vitro bioassay method for measuring LH activity was applied to male plasma. This method is based on the specific testosterone response to LH activity by interstitial cells from mouse testes. In contrast to assays conducted on female plasma, non-parallel response lines were obtained between serial dilutions of untreated male plasma and the International Reference Preparation for Human Pituitary Gonadotrophins FSH and LH/ICSH) for bioassay (code no. 69/104). In an attempt to eliminate this source of error, which would invalidate the assays, plasma was subjected to either ether extraction or charcoal adsorption prior to assay. While ether extraction was ineffective, charcoal treatment eliminated the source of non-parallelism. Evidence is presented indicating that the inclusion of a charcoal pre-treatment step provides an assay method for LH which fulfils the recognized criteria of reliability when applied to male plasma. An investigation of the likely causes of non-parallelism was undertaken by incubating mouse interstitial cells with various steroids and steroid sulphates at concentrations likely to be present in plasma. While most of the presumed precursors of testosterone were converted to testosterone, steroid sulphates (dehydroepiandrosterone sulphate and pregnenolone sulphate) at high concentrations as present in male plasma were the most active compounds in forming testosterone. However, the amount of testosterone produced from these precursors under controlled conditions was insufficient to account entirely for the deviation from parallelism observed with male plasma. Hence, the non-parallelism observed with untreated plasma samples cannot be entirely explained by the presence of steroidal testosterone precursors in male plasma."} {"id": "PMID:155387", "title": "Early changes in the arterial endothelium under various pathological conditions: an electron histochemical study with visualization of altered permeability using electron microscopic tracers.", "content": "The authors have studied the endothelial changes in the aorta and the arteries of heart, kidney and other organs in cholesterol fed rabbits and endotoxin administrated rats through electron histochemical and vascular clearance methods. The vascular changes are variable presumably due to the functional and morphological difference of vessels. The administration of cholesterol and endotoxin may result in increased vascular permeability which is directly related to the qualitative increase and decrease of hydrolytic enzymes in the vascular wall. The permeability of high molecular substances was enhanced with the widening of the intercellular space in contraction of endothelium and the changing of molecular structure of plasma membrane accompanied with plasma lipid, platelets and hemodynamic stress. This fact was confirmed by use of horseradish peroxidase and dextran fesin as tracers of different molecular sizes. The authors emphasize that direct injury and subsequent abnormal contraction of the endothelial cell may initiate increased permeability of plasma protein and lipid in the medial layer and eventually may develop and enhance arteriosclerosis.", "contents": "Early changes in the arterial endothelium under various pathological conditions: an electron histochemical study with visualization of altered permeability using electron microscopic tracers. The authors have studied the endothelial changes in the aorta and the arteries of heart, kidney and other organs in cholesterol fed rabbits and endotoxin administrated rats through electron histochemical and vascular clearance methods. The vascular changes are variable presumably due to the functional and morphological difference of vessels. The administration of cholesterol and endotoxin may result in increased vascular permeability which is directly related to the qualitative increase and decrease of hydrolytic enzymes in the vascular wall. The permeability of high molecular substances was enhanced with the widening of the intercellular space in contraction of endothelium and the changing of molecular structure of plasma membrane accompanied with plasma lipid, platelets and hemodynamic stress. This fact was confirmed by use of horseradish peroxidase and dextran fesin as tracers of different molecular sizes. The authors emphasize that direct injury and subsequent abnormal contraction of the endothelial cell may initiate increased permeability of plasma protein and lipid in the medial layer and eventually may develop and enhance arteriosclerosis."} {"id": "PMID:155388", "title": "Disease pattern among 942 mentally retarded persons in a Danish county.", "content": "An analytical description is presented of 942 mentally retarded persons from the county of West Zealand. The prevalence of mental retardation (i.e. persons who were registered with an IQ below 75) was 0.36%. Almost half of the patients were living in institutions. Of the patients 43% were women and 57% men. Important aetiological factors are listed. In almost one third of the patients, similar cases were present among the closest relatives; 30% of the patients were born as the fourth or subsequent child in the family; one sixth of the mothers were more than 35 years old at the birth of the handicapped child. Twenty-two percent of the patients with IQs below 50 had Down's syndrome. Seventeen percent of the patients had epilepsy had 11% cerebral palsy. In the central institution all patients had psychiatric or somatic complications.", "contents": "Disease pattern among 942 mentally retarded persons in a Danish county. An analytical description is presented of 942 mentally retarded persons from the county of West Zealand. The prevalence of mental retardation (i.e. persons who were registered with an IQ below 75) was 0.36%. Almost half of the patients were living in institutions. Of the patients 43% were women and 57% men. Important aetiological factors are listed. In almost one third of the patients, similar cases were present among the closest relatives; 30% of the patients were born as the fourth or subsequent child in the family; one sixth of the mothers were more than 35 years old at the birth of the handicapped child. Twenty-two percent of the patients with IQs below 50 had Down's syndrome. Seventeen percent of the patients had epilepsy had 11% cerebral palsy. In the central institution all patients had psychiatric or somatic complications."} {"id": "PMID:155389", "title": "Tryptophan-nicotinamide, imipramine and their combination in depression. A controlled study.", "content": "In a double-blind controlled study lasting 4 weeks 25 newly admitted severely depressed patients were randomly assigned to tryptophan-nicotinamide or imipramine or tryptophan-nicotinamide-imipramine combination. Nicotinamide was given to reduce peripheral breakdown of tryptophan. Although there were no substantial differences between the three treatments, the efficacy of tryptophan-nicotinamide tended to diminish after 2 weeks when the dose of tryptophan was increased from 4 g/day to 6 g/day and that of nicotinamide from 1.0 g/day to 1.5 g/day. The therapeutic response of patients treated with tryptophan-nicotinamide was significantly correlated with the rise in plasma tryptophan. For the tryptophan-nicotinamide-imipramine group, however, therapeutic response and rise in plasma tryptophan were negatively correlated, implying that tryptophan levels were too high in some patients. The data suggest that tryptophan-nicotamide may be as effective as imipramine in unipolar patients providing the dose is kept within the therapeutic window, and that at low doses it could also potentiate the action of tricyclic antidepressants. Bipolar patients seem to require higher doses of tryptophan than unipolar patients.", "contents": "Tryptophan-nicotinamide, imipramine and their combination in depression. A controlled study. In a double-blind controlled study lasting 4 weeks 25 newly admitted severely depressed patients were randomly assigned to tryptophan-nicotinamide or imipramine or tryptophan-nicotinamide-imipramine combination. Nicotinamide was given to reduce peripheral breakdown of tryptophan. Although there were no substantial differences between the three treatments, the efficacy of tryptophan-nicotinamide tended to diminish after 2 weeks when the dose of tryptophan was increased from 4 g/day to 6 g/day and that of nicotinamide from 1.0 g/day to 1.5 g/day. The therapeutic response of patients treated with tryptophan-nicotinamide was significantly correlated with the rise in plasma tryptophan. For the tryptophan-nicotinamide-imipramine group, however, therapeutic response and rise in plasma tryptophan were negatively correlated, implying that tryptophan levels were too high in some patients. The data suggest that tryptophan-nicotamide may be as effective as imipramine in unipolar patients providing the dose is kept within the therapeutic window, and that at low doses it could also potentiate the action of tricyclic antidepressants. Bipolar patients seem to require higher doses of tryptophan than unipolar patients."} {"id": "PMID:155386", "title": "[Properties of protamine-heparin complexes].", "content": "Protamine-heparin complexes have a considerable resistance to physical factors of the environment such as a high ion strength and acid or alkaline pH. Free protamine is digested by plasmin giving products with a greatly decreased ability to form complexes with heparin and lower antiheparin action. Bound protamine, on the other hand, is resistant to the action of plasmin as a result of which the enzyme does not release heparin from the complexes.", "contents": "[Properties of protamine-heparin complexes]. Protamine-heparin complexes have a considerable resistance to physical factors of the environment such as a high ion strength and acid or alkaline pH. Free protamine is digested by plasmin giving products with a greatly decreased ability to form complexes with heparin and lower antiheparin action. Bound protamine, on the other hand, is resistant to the action of plasmin as a result of which the enzyme does not release heparin from the complexes."} {"id": "PMID:155391", "title": "Clinical comparison of locetamic acid (cholebrine) and ipodate sodium (Orgrafin).", "content": "Locetamic acid (Cholebrine) and ipodate sodium (Oragrafin) were compared in a double blind study of 503 patients. The radiographs were evaluated for contrast density, visualization of common duct, gallstones, residual in the intestinal tract, and side effects. Cholebrine demonstrated better opacification, fewer repeat examinations, slightly greater common duct opacification, and more frequent visualization of gallstones. Oragrafin had less residue. Side effects were minimal with both contrast agents.", "contents": "Clinical comparison of locetamic acid (cholebrine) and ipodate sodium (Orgrafin). Locetamic acid (Cholebrine) and ipodate sodium (Oragrafin) were compared in a double blind study of 503 patients. The radiographs were evaluated for contrast density, visualization of common duct, gallstones, residual in the intestinal tract, and side effects. Cholebrine demonstrated better opacification, fewer repeat examinations, slightly greater common duct opacification, and more frequent visualization of gallstones. Oragrafin had less residue. Side effects were minimal with both contrast agents."} {"id": "PMID:155393", "title": "ECG pattern of left ventricular hypertrophy in nonobstructive hypertrophic cardiomyopathy: the significance of the mid-precordial changes.", "content": "A review of electrocardiograms from 33 patients with nonobstructive hypertrophic cardiomyopathy was made. In 22 patients there was noted a high QRS voltage, depression of the ST segment, and inversion of the T wave, satisfying the diagnostic criteria of left ventricular hypertrophy with the abnormal changes not only extending to the midprecordial leads but showing the most striking abnormal changes in Lead V4 in 20 patients. The frontal plane electrical axis was normal (around 60 degrees), with the most remarkable changes in Lead II. In the VCG, the magnitude of the QRS loop was increased and directed anteriorly and to the left, and the T loop was deviated posteriorly and to the right opposite the QRS loop. The asymmetric septal and apical hypertrophy was noted on echocardiography and/or angiocardiography. The coronary arteries were normal without significant obstruction in selective coronary angiography. It was postulated that the asymmetric septal and apical hypertrophy was reflected in this ECG pattern. The recognition of this ECG pattern provides pertinent information in the clinical detection of nonobstructive HCM.", "contents": "ECG pattern of left ventricular hypertrophy in nonobstructive hypertrophic cardiomyopathy: the significance of the mid-precordial changes. A review of electrocardiograms from 33 patients with nonobstructive hypertrophic cardiomyopathy was made. In 22 patients there was noted a high QRS voltage, depression of the ST segment, and inversion of the T wave, satisfying the diagnostic criteria of left ventricular hypertrophy with the abnormal changes not only extending to the midprecordial leads but showing the most striking abnormal changes in Lead V4 in 20 patients. The frontal plane electrical axis was normal (around 60 degrees), with the most remarkable changes in Lead II. In the VCG, the magnitude of the QRS loop was increased and directed anteriorly and to the left, and the T loop was deviated posteriorly and to the right opposite the QRS loop. The asymmetric septal and apical hypertrophy was noted on echocardiography and/or angiocardiography. The coronary arteries were normal without significant obstruction in selective coronary angiography. It was postulated that the asymmetric septal and apical hypertrophy was reflected in this ECG pattern. The recognition of this ECG pattern provides pertinent information in the clinical detection of nonobstructive HCM."} {"id": "PMID:155394", "title": "Influence of preoperative left ventricular function on results of homograft replacement of the aortic valve for aortic stenosis.", "content": "The effect of preoperative left ventricular function on early and late prognosis was assessed in 103 patients with aortic stenosis who underwent left ventricular cineangiography before homograft replacement of the aortic valve. The patients were separated into two groups: Group A (58 patients) with an ejection fraction of 0.46 or more and Group B (45 patients) with an ejection fraction of 0.45 or less. The two groups were compared with respect to clinical and hemodynamic data as well as operative result. There was poor correlation between clinical data and left ventricular function. In Group A there were three early deaths (5.2 percent) and three late deaths (5.2 percent) compared with no early and six late deaths (13.3 percent) in Group B during the follow-up period of 12 to 102 months (mean 43 months). Most patients in Group B showed considerable symptomatic improvement but less than that observed in Group A. Forty-two patients (13 in Group A and 29 in Group B) underwent repeat cardiac catheterization and coronary angiography. Improvement in left ventricular function as assessed by radial analysis of segmental wall motion and ejection fraction was observed in 20 of the 29 patients in Group B. Failure of left ventricular function to improve was associated with additional coronary artery disease in the majority of patients. It is concluded that poor left ventricular function does not increase the risk of aortic valve replacement for aortic stenosis and that improvement in left ventricular function can be expected in the majority of patients.", "contents": "Influence of preoperative left ventricular function on results of homograft replacement of the aortic valve for aortic stenosis. The effect of preoperative left ventricular function on early and late prognosis was assessed in 103 patients with aortic stenosis who underwent left ventricular cineangiography before homograft replacement of the aortic valve. The patients were separated into two groups: Group A (58 patients) with an ejection fraction of 0.46 or more and Group B (45 patients) with an ejection fraction of 0.45 or less. The two groups were compared with respect to clinical and hemodynamic data as well as operative result. There was poor correlation between clinical data and left ventricular function. In Group A there were three early deaths (5.2 percent) and three late deaths (5.2 percent) compared with no early and six late deaths (13.3 percent) in Group B during the follow-up period of 12 to 102 months (mean 43 months). Most patients in Group B showed considerable symptomatic improvement but less than that observed in Group A. Forty-two patients (13 in Group A and 29 in Group B) underwent repeat cardiac catheterization and coronary angiography. Improvement in left ventricular function as assessed by radial analysis of segmental wall motion and ejection fraction was observed in 20 of the 29 patients in Group B. Failure of left ventricular function to improve was associated with additional coronary artery disease in the majority of patients. It is concluded that poor left ventricular function does not increase the risk of aortic valve replacement for aortic stenosis and that improvement in left ventricular function can be expected in the majority of patients."} {"id": "PMID:155396", "title": "Familial occurrence of gastroschisis. Four new cases and review of the literature.", "content": "In two unrelated families, there was familial occurrence of gastroschisis. In one family, a boy and girl were affected and there was a family history of stillbirth, abortion, prematurity, and esophageal obstruction. In the second family, two boys were affected and there was a family history of spontaneous abortion, inguinal hernia, and umbilical hernia. The recurrence of gastroschisis, generally considered a sporadic congenital effect, suggests that the condition may be genetic in nature. Furthermore, the pedigree of one of the families suggests that gastroschisis may be a severe expression of umbilical hernia or other abdominal wall defects. Autosomal dominant inheritance with variable expressivity or multifactorial inheritance may explain the occurrence of gastroschisis in the two families. Thus, a family history of abdominal wall defects may increase the risk for gastroschisis.", "contents": "Familial occurrence of gastroschisis. Four new cases and review of the literature. In two unrelated families, there was familial occurrence of gastroschisis. In one family, a boy and girl were affected and there was a family history of stillbirth, abortion, prematurity, and esophageal obstruction. In the second family, two boys were affected and there was a family history of spontaneous abortion, inguinal hernia, and umbilical hernia. The recurrence of gastroschisis, generally considered a sporadic congenital effect, suggests that the condition may be genetic in nature. Furthermore, the pedigree of one of the families suggests that gastroschisis may be a severe expression of umbilical hernia or other abdominal wall defects. Autosomal dominant inheritance with variable expressivity or multifactorial inheritance may explain the occurrence of gastroschisis in the two families. Thus, a family history of abdominal wall defects may increase the risk for gastroschisis."} {"id": "PMID:155397", "title": "Acne vulgaris. Current concepts of pathogenesis and treatment.", "content": "Although the basic cause of acne vulgaris remains unknown, considerable data that concern its pathogenesis and that have been accumulated in recent years allow a rational and therapeutically successful approach to the management of this disorder. To date, there is no single treatment for acne. Therapy must be individualized, with appropriate variations and modifications as the degree or severity of this disorder fluctuates. Today, this goal can be achieved by proper selection of available medications, coupled with the cooperation of the patient, and the knowledge, continued interest, and enthusiasm of the physician and his staff.", "contents": "Acne vulgaris. Current concepts of pathogenesis and treatment. Although the basic cause of acne vulgaris remains unknown, considerable data that concern its pathogenesis and that have been accumulated in recent years allow a rational and therapeutically successful approach to the management of this disorder. To date, there is no single treatment for acne. Therapy must be individualized, with appropriate variations and modifications as the degree or severity of this disorder fluctuates. Today, this goal can be achieved by proper selection of available medications, coupled with the cooperation of the patient, and the knowledge, continued interest, and enthusiasm of the physician and his staff."} {"id": "PMID:155398", "title": "Steroid-sulfatase deficiency in sex-linked ichthyosis.", "content": "Steroid-sulfatase activity was absent in the cultured fibroblasts of nine affected members of eight families with sex-linked ichthyosis. An intermediate value of enzyme activity was found in an obligate heterozygote and a normal value in a patient with ichthyosis vulgaris. Cultured epidermal cells of an affected individual also had no enzyme activity, while normal cultured epidermal cells did.", "contents": "Steroid-sulfatase deficiency in sex-linked ichthyosis. Steroid-sulfatase activity was absent in the cultured fibroblasts of nine affected members of eight families with sex-linked ichthyosis. An intermediate value of enzyme activity was found in an obligate heterozygote and a normal value in a patient with ichthyosis vulgaris. Cultured epidermal cells of an affected individual also had no enzyme activity, while normal cultured epidermal cells did."} {"id": "PMID:155399", "title": "Abnormal skin fibroblast cytogenetics in four dysmorphic patients with normal lymphocyte chromosomes.", "content": "Four patients with features suggestive of chromosome disorders but with normal lymphocyte karyotypes were found to have chromosome aberrations in skin fibroblast karyotypes. Although mosaicism for chromosome abnormalities in lymphocyte cultures is common, apparent restriction of mosaicism to one tissue is unusual. We suggest that after examination of lymphocyte karyotypes, certain patients warrant cytogenetic evaluation of a second tissue, usually cultured skin fibroblasts.", "contents": "Abnormal skin fibroblast cytogenetics in four dysmorphic patients with normal lymphocyte chromosomes. Four patients with features suggestive of chromosome disorders but with normal lymphocyte karyotypes were found to have chromosome aberrations in skin fibroblast karyotypes. Although mosaicism for chromosome abnormalities in lymphocyte cultures is common, apparent restriction of mosaicism to one tissue is unusual. We suggest that after examination of lymphocyte karyotypes, certain patients warrant cytogenetic evaluation of a second tissue, usually cultured skin fibroblasts."} {"id": "PMID:155402", "title": "Phosphorylation of a bovine cardiac actin complex.", "content": "A bovine cardiac actin-tropomyosin-troponin complex was phosphorylated in the presence of [gamma-32P]ATP, Mg2+, adenosine 3',5'-monophosphate (cyclic AMP), and bovine cardiac cyclic-AMP-dependent protein kinase. Approximately 81% of the [32P]phosphate incorporated was identified as phosphoserine and phosphothreonine. Gel electrophoresis studies showed that 55% of the [32P]phosphate was associated with the inhibitory component of troponin (Tn-I) and 24% with a protein resembling the tropomyosin-binding component of troponin in the actin complex, respectively. The phosphorylation of Tn-I in the actin complex was inhibited 30% when Ca2+ was increased from 0.1 to 50 muM, but phosphorylation of other components was not affected by increasing Ca2+ concentration. Half-maximal calcium activation of the ATPase activity of reconstituted actomyosins made with the [32P]phosphorylated cardiac actin complex and cardiac myosin was shifted to Ca2+ values higher than those of actomyosins made with the nonphosphorylated actin complex.", "contents": "Phosphorylation of a bovine cardiac actin complex. A bovine cardiac actin-tropomyosin-troponin complex was phosphorylated in the presence of [gamma-32P]ATP, Mg2+, adenosine 3',5'-monophosphate (cyclic AMP), and bovine cardiac cyclic-AMP-dependent protein kinase. Approximately 81% of the [32P]phosphate incorporated was identified as phosphoserine and phosphothreonine. Gel electrophoresis studies showed that 55% of the [32P]phosphate was associated with the inhibitory component of troponin (Tn-I) and 24% with a protein resembling the tropomyosin-binding component of troponin in the actin complex, respectively. The phosphorylation of Tn-I in the actin complex was inhibited 30% when Ca2+ was increased from 0.1 to 50 muM, but phosphorylation of other components was not affected by increasing Ca2+ concentration. Half-maximal calcium activation of the ATPase activity of reconstituted actomyosins made with the [32P]phosphorylated cardiac actin complex and cardiac myosin was shifted to Ca2+ values higher than those of actomyosins made with the nonphosphorylated actin complex."} {"id": "PMID:155403", "title": "Anion-stimulated ATPase activity of brush border from rat small intestine.", "content": "Differential centrifugation of rat small intestinal homogenates produced a crude brush border (BB) fraction that was enriched 15-fold for the marker enzymes, alkaline phosphatase and sucrase; contamination with mitochondrial enzymes, monoamine oxidase and succinate dehydrogenase, was minimal. ATP hydrolysis by this BB fraction was stimulated by addition of several anions to the incubation medium: HCO3 and Cl were equally effective in this regard, with NO3, NO2, SO4, and acetate being less stimulatory. SCN and CNO inhibited ATPase activity, whereas the divalent anion SO3 was stimulatory at low concentrations (less than 25 mM) but inhibitory at 100 mM. Maximum anion stimulation was observed at a Mg concentration of 0.5 mM, and pH optimum was 8.5. Kinetic analysis showed that HCO3 increased the Vmax without altering the Km for ATP; the Ka for this effect of HCO3 was 35 mM. This enzyme activity was completely inhibited by 20 mM L-phenylalanine, 10 mM L-cysteine, and 3 mM EDTA, compounds that also inhibited intestinal alkaline phosphatase. These results demonstrate the presence of anion-stimulated ATPase activity in rat small intestinal brush border and suggest that this activity may be related to intestinal alkaline phosphatase. The role of this enzyme in intestinal transport is not known, but could relate to the regulation of intestinal absorption and secretion.", "contents": "Anion-stimulated ATPase activity of brush border from rat small intestine. Differential centrifugation of rat small intestinal homogenates produced a crude brush border (BB) fraction that was enriched 15-fold for the marker enzymes, alkaline phosphatase and sucrase; contamination with mitochondrial enzymes, monoamine oxidase and succinate dehydrogenase, was minimal. ATP hydrolysis by this BB fraction was stimulated by addition of several anions to the incubation medium: HCO3 and Cl were equally effective in this regard, with NO3, NO2, SO4, and acetate being less stimulatory. SCN and CNO inhibited ATPase activity, whereas the divalent anion SO3 was stimulatory at low concentrations (less than 25 mM) but inhibitory at 100 mM. Maximum anion stimulation was observed at a Mg concentration of 0.5 mM, and pH optimum was 8.5. Kinetic analysis showed that HCO3 increased the Vmax without altering the Km for ATP; the Ka for this effect of HCO3 was 35 mM. This enzyme activity was completely inhibited by 20 mM L-phenylalanine, 10 mM L-cysteine, and 3 mM EDTA, compounds that also inhibited intestinal alkaline phosphatase. These results demonstrate the presence of anion-stimulated ATPase activity in rat small intestinal brush border and suggest that this activity may be related to intestinal alkaline phosphatase. The role of this enzyme in intestinal transport is not known, but could relate to the regulation of intestinal absorption and secretion."} {"id": "PMID:155404", "title": "Extracellular space, water, and ion concentration in the hypertrophied rat myocardium.", "content": "Extracellular space (ECS), water, and intracellular ion concentration were determined in the normal and hypertrophied rat myocardium. Theoretical measurements of myocardial ECS based on a mathematical model (9.31%) closely approximated the observed results in the normal myocardium (12.8%) and hypertrophied myocardium (11.7%). Observed results confirmed theoretical considerations of no change in ECS with hypertrophy. ECS and water content were higher in the right ventricle than the left ventricle, but intracellular electrolytes remained unchanged. Myocardial hypertrophy did not alter these relationships.", "contents": "Extracellular space, water, and ion concentration in the hypertrophied rat myocardium. Extracellular space (ECS), water, and intracellular ion concentration were determined in the normal and hypertrophied rat myocardium. Theoretical measurements of myocardial ECS based on a mathematical model (9.31%) closely approximated the observed results in the normal myocardium (12.8%) and hypertrophied myocardium (11.7%). Observed results confirmed theoretical considerations of no change in ECS with hypertrophy. ECS and water content were higher in the right ventricle than the left ventricle, but intracellular electrolytes remained unchanged. Myocardial hypertrophy did not alter these relationships."} {"id": "PMID:155405", "title": "Fructose-6-phosphate substrate cycling and glucose and insulin regulation of gluconeogenesis in vivo.", "content": "The question whether glucose or insulin regulates gluconeogenesis by effecting changes in the fructose-6-phosphate (F-6-P) substrate cycle (phosphofructokinase (PFK), fructose-1,6-diphosphatase (FDPase)) was investigated in vivo in fasted normal rats using [3-3H,U-14C]- or [3-3H,6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because 3H loss from the liver hexose phosphate pool is limited by the activities of PFK and FDPase during gluconeogenesis and glycolysis, respectively. The 3H/14C ratio was corrected where necessary for glucose or insulin-induced changes in reincorporation of 14C from C-6 to C-1-3 of plasma glucose. A glucose infusion producing hyperglycemia and insulinemia was accompanied by decreased hepatic glucose production and diminished F-6-P substrate cycling, i.e., decreased FDPase activity. When insulin was infused along with glucose to produce high plasma insulin levels and avoid hypo- or hyperglycemia, the 3H/14C decay rate did not change, suggesting that the hormone does not influence basal rates of gluconeogenesis or PFK or FDPase activities. These in vivo results suggest that increased blood glucose levels inhibit gluconeogenesis and depress F-6-P substrate cycling. Whether these cycle changes constitute primary regulatory actions of glucose or occur secondarily to other metabolic events resulting from excess hexose (e.g., increased glycogen synthetase activity) cannot now be concluded.", "contents": "Fructose-6-phosphate substrate cycling and glucose and insulin regulation of gluconeogenesis in vivo. The question whether glucose or insulin regulates gluconeogenesis by effecting changes in the fructose-6-phosphate (F-6-P) substrate cycle (phosphofructokinase (PFK), fructose-1,6-diphosphatase (FDPase)) was investigated in vivo in fasted normal rats using [3-3H,U-14C]- or [3-3H,6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because 3H loss from the liver hexose phosphate pool is limited by the activities of PFK and FDPase during gluconeogenesis and glycolysis, respectively. The 3H/14C ratio was corrected where necessary for glucose or insulin-induced changes in reincorporation of 14C from C-6 to C-1-3 of plasma glucose. A glucose infusion producing hyperglycemia and insulinemia was accompanied by decreased hepatic glucose production and diminished F-6-P substrate cycling, i.e., decreased FDPase activity. When insulin was infused along with glucose to produce high plasma insulin levels and avoid hypo- or hyperglycemia, the 3H/14C decay rate did not change, suggesting that the hormone does not influence basal rates of gluconeogenesis or PFK or FDPase activities. These in vivo results suggest that increased blood glucose levels inhibit gluconeogenesis and depress F-6-P substrate cycling. Whether these cycle changes constitute primary regulatory actions of glucose or occur secondarily to other metabolic events resulting from excess hexose (e.g., increased glycogen synthetase activity) cannot now be concluded."} {"id": "PMID:155406", "title": "Effects of starvation and diabetes on protein synthesis in lung.", "content": "Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed.", "contents": "Effects of starvation and diabetes on protein synthesis in lung. Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed."} {"id": "PMID:155407", "title": "Natural biventricular hypertrophy in normotensive rats. I. Physical and hemodynamic characteristics.", "content": "The Wistar-Kyoto strain of normotensive rats (WKY) is being used as a control animal for studies involving the spontaneously hypertensive rats (SHR). A subset of the WKY demonstrating an inheritable transmission of biventricular cardiac hypertrophy (BVH) has been identified. The cardiac enlargement is pronounced, with right and left ventricular weights greater than twice normal in some animals. This natural development of BVH appears to be in response to an increased cardiac output. Blood pressure is normal and, therefore, peripheral resistance is reduced. Left ventricular injection of 15-micrometer radioactively labeled microspheres demonstrated that WKY with BVH had a substantial shunt fraction of their cardiac output (45 +/- 7% radioactivity recovered in the lungs vs. 3 +/- 2% in normal WKY). This subset of WKY with BVH provides a natural model of volume-load hypertrophy. In addition, investigators using the WKY for comparison with SHR should exclude animals with BVH.", "contents": "Natural biventricular hypertrophy in normotensive rats. I. Physical and hemodynamic characteristics. The Wistar-Kyoto strain of normotensive rats (WKY) is being used as a control animal for studies involving the spontaneously hypertensive rats (SHR). A subset of the WKY demonstrating an inheritable transmission of biventricular cardiac hypertrophy (BVH) has been identified. The cardiac enlargement is pronounced, with right and left ventricular weights greater than twice normal in some animals. This natural development of BVH appears to be in response to an increased cardiac output. Blood pressure is normal and, therefore, peripheral resistance is reduced. Left ventricular injection of 15-micrometer radioactively labeled microspheres demonstrated that WKY with BVH had a substantial shunt fraction of their cardiac output (45 +/- 7% radioactivity recovered in the lungs vs. 3 +/- 2% in normal WKY). This subset of WKY with BVH provides a natural model of volume-load hypertrophy. In addition, investigators using the WKY for comparison with SHR should exclude animals with BVH."} {"id": "PMID:155409", "title": "Reconstruction of the anterior cruciate ligament in the dog. Comparison of results obtained with three different porous synthetic materials.", "content": "The anterior cruciate ligaments in 17 knees of 12 mongrel dogs were replaced with one of three porous minimally reactive prosthetic (synthetic) materials. The results show that while the porous materials support the ingrowth of fibrous tissue from the bone of the dog's knee, fatigue failure occurred before sufficient fibrous tissue was incorporated to reconstitute a functional ligament. Further laboratory investigation is necessary before prosthetic materials, currently available, can be used in the unstable human knee.", "contents": "Reconstruction of the anterior cruciate ligament in the dog. Comparison of results obtained with three different porous synthetic materials. The anterior cruciate ligaments in 17 knees of 12 mongrel dogs were replaced with one of three porous minimally reactive prosthetic (synthetic) materials. The results show that while the porous materials support the ingrowth of fibrous tissue from the bone of the dog's knee, fatigue failure occurred before sufficient fibrous tissue was incorporated to reconstitute a functional ligament. Further laboratory investigation is necessary before prosthetic materials, currently available, can be used in the unstable human knee."} {"id": "PMID:155413", "title": "Experimental uveitis in isolated humoral and cellular immunity.", "content": "Passive transfer of homologous immune serum in rabbits followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the Arthus-type reaction. Clinically and histologically, the reaction was maximal 24 h after antigen injection. The histologically observed cell infiltration consisted predominantly of polymorphonuclear leukocytes. Passive transfer of sensitized homologous thymocytes followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the delayed-type hypersensitivity reaction. Tissue infiltration of polymorphonuclear cells as well as mononuclear cells occurred predominantly during the first day following antigen injection. An exudate containing almost exclusively eosinophils was present in the aqueous humor and/or vitreous body of most of these rabbits. During the second day an increase in the ratio monomuclear cells/polymorphonuclear cells could be observed.", "contents": "Experimental uveitis in isolated humoral and cellular immunity. Passive transfer of homologous immune serum in rabbits followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the Arthus-type reaction. Clinically and histologically, the reaction was maximal 24 h after antigen injection. The histologically observed cell infiltration consisted predominantly of polymorphonuclear leukocytes. Passive transfer of sensitized homologous thymocytes followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the delayed-type hypersensitivity reaction. Tissue infiltration of polymorphonuclear cells as well as mononuclear cells occurred predominantly during the first day following antigen injection. An exudate containing almost exclusively eosinophils was present in the aqueous humor and/or vitreous body of most of these rabbits. During the second day an increase in the ratio monomuclear cells/polymorphonuclear cells could be observed."} {"id": "PMID:155415", "title": "Gonorrhea. Center for Disease Control recommended treatment schedules, 1979.", "content": "These recommendations specify appropriate treatment, including dosage of antibiotics for uncomplicated gonococcal infections in adults, infections with penicillinase-producing Neisseria gonorrhoeae, acute salpingitis, acute epididymitis, disseminated gonococcal infections, and gonococcal infections in pediatric patients (including neonatal infections). Special attention is given to important diagnostic considerations, relation of gonococcal infections to concomitant venereal infections, treatment of sexual partners, follow-up, treatment failures, treatments not recommended, allergic problems in treatment, needs for hospitalization, and prevention of gonococcal ophthalmia. Attention is called to the importance of using no less than the recommended dosages of antibiotics.", "contents": "Gonorrhea. Center for Disease Control recommended treatment schedules, 1979. These recommendations specify appropriate treatment, including dosage of antibiotics for uncomplicated gonococcal infections in adults, infections with penicillinase-producing Neisseria gonorrhoeae, acute salpingitis, acute epididymitis, disseminated gonococcal infections, and gonococcal infections in pediatric patients (including neonatal infections). Special attention is given to important diagnostic considerations, relation of gonococcal infections to concomitant venereal infections, treatment of sexual partners, follow-up, treatment failures, treatments not recommended, allergic problems in treatment, needs for hospitalization, and prevention of gonococcal ophthalmia. Attention is called to the importance of using no less than the recommended dosages of antibiotics."} {"id": "PMID:155416", "title": "[Repeated abortions, sterility and systemic dysimmunopathy (author's transl)].", "content": "A patient with lupus disease had a previous medical history of five recurrent temporary bouts of thrombopenia which were followed by spontaneous abortions. This raises the two-fold problem of the relationship between circulating immune complexes disease and thrombopenia, and dysimmunopathy and pregnancy disorders. The hypothesis is raised of a trophoblastic necrotizing angeitis due to abnormal immunity processes involved in some cases of sterility, spontaneous abortions, and even nephropathies during pregnancy.", "contents": "[Repeated abortions, sterility and systemic dysimmunopathy (author's transl)]. A patient with lupus disease had a previous medical history of five recurrent temporary bouts of thrombopenia which were followed by spontaneous abortions. This raises the two-fold problem of the relationship between circulating immune complexes disease and thrombopenia, and dysimmunopathy and pregnancy disorders. The hypothesis is raised of a trophoblastic necrotizing angeitis due to abnormal immunity processes involved in some cases of sterility, spontaneous abortions, and even nephropathies during pregnancy."} {"id": "PMID:155419", "title": "Heart muscle mechanics.", "content": "The goal implicit in the research reviewed above is to describe the contractile behavior of heart muscle in terms of crossbridge and filament behavior. It is necessary to elucidate these details in cardiac muscle because of the distinct biochemical differences between skeletal and cardiac myosin. As is evident in this review, significant advances have been made toward describing unique mechanical properties of cardiac muscle crossbridges. Several major problems now require attention: (a) Activation parameters are labile, making mechanical measurements sensitive to measurement perturbation; (b) significant structural inhomogeneities at the cellular and sarcomere level prevent precise assignment of externally measured force to internal structures (force generators, passive elements) within whole cardiac muscle and individual cells; (c) high resting stiffness and forces of poorly understood origin and properties confound attempts to interpret force measurements and dynamics. The differences between heart and skeletal muscle myosin may provide the means for identifying structural counterparts of the Huxley-Simmons model (33); they may also be useful in evaluating the electrostatic and quantum-mechanical models.", "contents": "Heart muscle mechanics. The goal implicit in the research reviewed above is to describe the contractile behavior of heart muscle in terms of crossbridge and filament behavior. It is necessary to elucidate these details in cardiac muscle because of the distinct biochemical differences between skeletal and cardiac myosin. As is evident in this review, significant advances have been made toward describing unique mechanical properties of cardiac muscle crossbridges. Several major problems now require attention: (a) Activation parameters are labile, making mechanical measurements sensitive to measurement perturbation; (b) significant structural inhomogeneities at the cellular and sarcomere level prevent precise assignment of externally measured force to internal structures (force generators, passive elements) within whole cardiac muscle and individual cells; (c) high resting stiffness and forces of poorly understood origin and properties confound attempts to interpret force measurements and dynamics. The differences between heart and skeletal muscle myosin may provide the means for identifying structural counterparts of the Huxley-Simmons model (33); they may also be useful in evaluating the electrostatic and quantum-mechanical models."} {"id": "PMID:155420", "title": "Molecular aspects of cardiac hypertrophy.", "content": "Despite continuous interest in cardiac hypertrophy, our knowledge of its molecular aspects is still elementary. Recently, however, several advancements of particular interest have been made: (a) Nuclei of muscle and nonmuscle cells have been separated, allowing for the first time the study of nuclear activity in specified cells (18). (b) Cardiac growth induced by pressure-overload (72) or by hormone treatment (26) has been shown to lead to myosin of altered ATPase, and strong evidence suggests that new species of myosin molecules thus appear. (c) The basis for assessment of protein synthesis and degradation has been established (46, 48). (d) Methods are being developed to supplement radioautography in evaluating cell proliferation (42, 59, 69). (e) In spontaneously hypertensive rats it has been shown that blood pressure might not be the sole factor responsible for cardiac enlargement, but that hypertrophy can be the result of genetic cardiovascular abnormality (19, 66). (f) A hypothesis relating the extent of energy utilization to the nuclear activity via NAD+ metabolism has been proposed, which allows for experimental verification (43).", "contents": "Molecular aspects of cardiac hypertrophy. Despite continuous interest in cardiac hypertrophy, our knowledge of its molecular aspects is still elementary. Recently, however, several advancements of particular interest have been made: (a) Nuclei of muscle and nonmuscle cells have been separated, allowing for the first time the study of nuclear activity in specified cells (18). (b) Cardiac growth induced by pressure-overload (72) or by hormone treatment (26) has been shown to lead to myosin of altered ATPase, and strong evidence suggests that new species of myosin molecules thus appear. (c) The basis for assessment of protein synthesis and degradation has been established (46, 48). (d) Methods are being developed to supplement radioautography in evaluating cell proliferation (42, 59, 69). (e) In spontaneously hypertensive rats it has been shown that blood pressure might not be the sole factor responsible for cardiac enlargement, but that hypertrophy can be the result of genetic cardiovascular abnormality (19, 66). (f) A hypothesis relating the extent of energy utilization to the nuclear activity via NAD+ metabolism has been proposed, which allows for experimental verification (43)."} {"id": "PMID:155418", "title": "Modulation of membrane-bound enzyme activity by binding of antibodies to major histocompatibility complex antigens.", "content": "The preparation of right side-out vesicles from mouse plasmocytoma plasma membranes can be used to study the early functionnal events of the plasma membrane upon binding of ligands. Activation of two membrane-bound enzymes, 5'-nucleotidase and Na+/K+ ATPase, induced specifically by several anti-H-2 antisera was investigated. A simultaneous stimulation of these two enzymes was reported at high dilutions of antisera directed against antigens of the MHC. Comparison between the enzyme activation test and the classical cytotoxicity test showed the former being more sensitive than the latter by at least one order of magnitude. A structural coordination between some histocompatibility antigens and/or other cell surface receptors and the membrane-bound enzymes could be envisionned for the initiation of lymphocyte activation.", "contents": "Modulation of membrane-bound enzyme activity by binding of antibodies to major histocompatibility complex antigens. The preparation of right side-out vesicles from mouse plasmocytoma plasma membranes can be used to study the early functionnal events of the plasma membrane upon binding of ligands. Activation of two membrane-bound enzymes, 5'-nucleotidase and Na+/K+ ATPase, induced specifically by several anti-H-2 antisera was investigated. A simultaneous stimulation of these two enzymes was reported at high dilutions of antisera directed against antigens of the MHC. Comparison between the enzyme activation test and the classical cytotoxicity test showed the former being more sensitive than the latter by at least one order of magnitude. A structural coordination between some histocompatibility antigens and/or other cell surface receptors and the membrane-bound enzymes could be envisionned for the initiation of lymphocyte activation."} {"id": "PMID:155427", "title": "The arthritic in an urban environment.", "content": "Ninety-five patients with rheumatoid arthritis or osteoarthrosis were interviewed and questioned in their homes, being randomly selected from 354 outpatients with these diseases. The findings were compared with answers from 30 matched able-bodied controls. The handicapped were mainly female and elderly; over half were severely or appreciably handicapped; nearly one-third lived alone. The average weekly income of these households was pound25, at least pound6 a week less than their age-matched counterparts. Very few subjects lived in adapted or specially designed housing, and half the housing had at least 2 steps to street level. A third of the sample could not walk more than 10 yards (9 m), and only half could walk 100 yards (90 m); yet only one-third had a bus stop, one-quarter a local park, and one-third a local shop within this distance. One-third of the patients could not shop for themselves. Powered wheelchairs were not used. Buses were rarely or never used by nearly half these arthritics because of severe disability. Cars were owned by less than a quarter of the sample, and only by those financially better off. Over a third were unable to get a lift when wanted. Cars ameliorated much of the frustration and lack of social contact caused by physical disability. Adequate financing would enable those with severe disability to engage in normal activities. Better designed buses stopping nearer the homes of handicapped would improve independence for those less severely disabled. Correct siting of mobility housing, shops, community facilities, and parks would be greatly appreciated, as would removal of all unnecessary steps and kerbs.", "contents": "The arthritic in an urban environment. Ninety-five patients with rheumatoid arthritis or osteoarthrosis were interviewed and questioned in their homes, being randomly selected from 354 outpatients with these diseases. The findings were compared with answers from 30 matched able-bodied controls. The handicapped were mainly female and elderly; over half were severely or appreciably handicapped; nearly one-third lived alone. The average weekly income of these households was pound25, at least pound6 a week less than their age-matched counterparts. Very few subjects lived in adapted or specially designed housing, and half the housing had at least 2 steps to street level. A third of the sample could not walk more than 10 yards (9 m), and only half could walk 100 yards (90 m); yet only one-third had a bus stop, one-quarter a local park, and one-third a local shop within this distance. One-third of the patients could not shop for themselves. Powered wheelchairs were not used. Buses were rarely or never used by nearly half these arthritics because of severe disability. Cars were owned by less than a quarter of the sample, and only by those financially better off. Over a third were unable to get a lift when wanted. Cars ameliorated much of the frustration and lack of social contact caused by physical disability. Adequate financing would enable those with severe disability to engage in normal activities. Better designed buses stopping nearer the homes of handicapped would improve independence for those less severely disabled. Correct siting of mobility housing, shops, community facilities, and parks would be greatly appreciated, as would removal of all unnecessary steps and kerbs."} {"id": "PMID:155428", "title": "Diabetes mellitus and neuropathy following Vacor ingestion in man.", "content": "Two patients ingested Vacor, a rodenticide containing the active ingredient N-3 pyridylmethyl-N'-p-nitrophenyl urea. Both patients developed ketosis-prone diabetes mellitus and severe autonomic neuropathy. Niacinamide therapy given nine hours after Vacor ingestion in one patient and 14 hours after ingestion in the other was not successful in preventing these sequelae. Physicians need to be aware of the toxicity of Vacor, and the potential therapeutic benefit of early niacinamide therapy.", "contents": "Diabetes mellitus and neuropathy following Vacor ingestion in man. Two patients ingested Vacor, a rodenticide containing the active ingredient N-3 pyridylmethyl-N'-p-nitrophenyl urea. Both patients developed ketosis-prone diabetes mellitus and severe autonomic neuropathy. Niacinamide therapy given nine hours after Vacor ingestion in one patient and 14 hours after ingestion in the other was not successful in preventing these sequelae. Physicians need to be aware of the toxicity of Vacor, and the potential therapeutic benefit of early niacinamide therapy."} {"id": "PMID:155429", "title": "[Familial congenital muscular dystrophy caused by phosphofructokinase deficiency].", "content": "Two children, born to related parents, presented since birth a muscular defect rapidly complicated by painful joint stiffness. The oldest child died at 6 months of age, from respiratory complications. The second-14 month old- does not sit without support. The muscle fibres are of unequal calibre and numerous fibres have under-sarcolemmal PAS positive areas contain glycogen, as seen on electron microscopy. In the second patient, the biochemical analysis showed a moderate glycogen accumulation and muscular enzymatic studies demonstrated an isolated and major deficiency in phosphofructokinase activity. Activity was normal in red blood cells and in fibroblasts cultured in vitro. Hence, these cases should be distinguished from formerly reported cases of phosphofructokinase deficiency. This type of P.F.K. deficiency should be looked for in patients with severe congenital muscular dystrophy and early joint involvement.", "contents": "[Familial congenital muscular dystrophy caused by phosphofructokinase deficiency]. Two children, born to related parents, presented since birth a muscular defect rapidly complicated by painful joint stiffness. The oldest child died at 6 months of age, from respiratory complications. The second-14 month old- does not sit without support. The muscle fibres are of unequal calibre and numerous fibres have under-sarcolemmal PAS positive areas contain glycogen, as seen on electron microscopy. In the second patient, the biochemical analysis showed a moderate glycogen accumulation and muscular enzymatic studies demonstrated an isolated and major deficiency in phosphofructokinase activity. Activity was normal in red blood cells and in fibroblasts cultured in vitro. Hence, these cases should be distinguished from formerly reported cases of phosphofructokinase deficiency. This type of P.F.K. deficiency should be looked for in patients with severe congenital muscular dystrophy and early joint involvement."} {"id": "PMID:155430", "title": "Studies on the human mixed lymphocyte culture. I. The influence of the irradiated autogenic and allogenic lymphocytes on DNA synthesis.", "content": "Fourteen patients with chronic renal failure and their prospective living donors were examined. DNA uptake by donors' monocultures, recipients' monocultures and mixed cultures was measured. The influence of X-ray treated cells on proliferative capacity of untreated cells in these three types of cultures was studied. The suppressing effect of irradiated cells was found in 52%, the enhancing one in 7% and no effect was observed in 41% of lymphocyte cultures. The possible explanations of the findings are discussed.", "contents": "Studies on the human mixed lymphocyte culture. I. The influence of the irradiated autogenic and allogenic lymphocytes on DNA synthesis. Fourteen patients with chronic renal failure and their prospective living donors were examined. DNA uptake by donors' monocultures, recipients' monocultures and mixed cultures was measured. The influence of X-ray treated cells on proliferative capacity of untreated cells in these three types of cultures was studied. The suppressing effect of irradiated cells was found in 52%, the enhancing one in 7% and no effect was observed in 41% of lymphocyte cultures. The possible explanations of the findings are discussed."} {"id": "PMID:155431", "title": "Studies on the human mixed lymphocyte culture. II. Comparison of one-way and two-way test performed on lymphocytes of patients with end-stage renal failure and their prospective living donors.", "content": "The results of DNA synthesis in human one-way and two-way mixed lymphocyte cultures were compared. Twenty patients with chronic renal failure and their twenty six prospective living donors were investigated. Statistical correlation was found on the level alpha = 0.01 between the stimulation index value calculated for one-way and two-way technique. Two-way MLC, the rapid and simple and simple assay detecting lymphocyte activation is a very useful tissue typing test.", "contents": "Studies on the human mixed lymphocyte culture. II. Comparison of one-way and two-way test performed on lymphocytes of patients with end-stage renal failure and their prospective living donors. The results of DNA synthesis in human one-way and two-way mixed lymphocyte cultures were compared. Twenty patients with chronic renal failure and their twenty six prospective living donors were investigated. Statistical correlation was found on the level alpha = 0.01 between the stimulation index value calculated for one-way and two-way technique. Two-way MLC, the rapid and simple and simple assay detecting lymphocyte activation is a very useful tissue typing test."} {"id": "PMID:155433", "title": "Immunosuppressive effect of concanavalin-A. I. Suppression of generation of cytotoxic lymphocytes in MLC.", "content": "The effect of Con-A on the generation of cytotoxic lymphocytes (CL) in one way MLC was studied using mouse model. Mitogenic doses of Con-A substantially inhibited primary and secondary CL responses. Spleen cells after in vivo activation by Con-A revealed complete lack of ability to respond in allogeneic MLC. When such cells were added to normal responding cells, even at low proportion, CL generation in primary MLC was also diminished. These observations support the hypothesis that immunosuppressive effect of Con-A is exerted by stimulation of suppressor cells.", "contents": "Immunosuppressive effect of concanavalin-A. I. Suppression of generation of cytotoxic lymphocytes in MLC. The effect of Con-A on the generation of cytotoxic lymphocytes (CL) in one way MLC was studied using mouse model. Mitogenic doses of Con-A substantially inhibited primary and secondary CL responses. Spleen cells after in vivo activation by Con-A revealed complete lack of ability to respond in allogeneic MLC. When such cells were added to normal responding cells, even at low proportion, CL generation in primary MLC was also diminished. These observations support the hypothesis that immunosuppressive effect of Con-A is exerted by stimulation of suppressor cells."} {"id": "PMID:155434", "title": "The appearance of factors influencing migration of lymphocytes (LyMIF and LyMSF) in rabbit mixed lymphocyte cultures.", "content": "In vitro migration of mixtures of peripheral blood lymphocytes derived from 26 pairs of rabbits was significantly suppressed in 73% of cultures, significantly enhanced in 4% and unchanged in 23%, as compared to the corresponding monocultures. Sensitization of 26 rabbits by kidney graft resulted in more frequent appearance of migration enhancing factor. Six days after grafting 54% of donor-recipient mixed cultures showed enhancement of migration, 31% inhibition and 15% no effect. No enhancing factors were produced on the 9th day.", "contents": "The appearance of factors influencing migration of lymphocytes (LyMIF and LyMSF) in rabbit mixed lymphocyte cultures. In vitro migration of mixtures of peripheral blood lymphocytes derived from 26 pairs of rabbits was significantly suppressed in 73% of cultures, significantly enhanced in 4% and unchanged in 23%, as compared to the corresponding monocultures. Sensitization of 26 rabbits by kidney graft resulted in more frequent appearance of migration enhancing factor. Six days after grafting 54% of donor-recipient mixed cultures showed enhancement of migration, 31% inhibition and 15% no effect. No enhancing factors were produced on the 9th day."} {"id": "PMID:155435", "title": "The effect of ATG treatment on LyMIF and LyMSF production in mixed lymphocyte cultures of rabbits after renal allotransplantation.", "content": "Rabbit lymphocytes, settled up in microcappillary tubes migrate into culture medium. In the previous communication we have shown that migration of mixture of lymphocytes derived from two blood donors was significantly inferior in 73% of cultures as compared to the corresponding monocultures. 4% of mixed cultures exhibited significant enhancement of migration and in 23% no effects were seen. Use of lymphocytes from rabbits 4-6 days after kidney allotransplantation and their corresponding donors resulted in conversion of this ratio. Percentage of cultures exhibiting enhancement of migration (production LyMSF) rose to 39, 46% of cultures were inhibited (produced LyMIF) and 15% did not show any significant effect. Treatment of kidney recipients with ATG exerted strong inhibitory effect on the appearance of LyMSF and on the appearance of LyMIF in mixed cultures. These results suggested that LyMIF and LyMSF were produced by separate cell populations.", "contents": "The effect of ATG treatment on LyMIF and LyMSF production in mixed lymphocyte cultures of rabbits after renal allotransplantation. Rabbit lymphocytes, settled up in microcappillary tubes migrate into culture medium. In the previous communication we have shown that migration of mixture of lymphocytes derived from two blood donors was significantly inferior in 73% of cultures as compared to the corresponding monocultures. 4% of mixed cultures exhibited significant enhancement of migration and in 23% no effects were seen. Use of lymphocytes from rabbits 4-6 days after kidney allotransplantation and their corresponding donors resulted in conversion of this ratio. Percentage of cultures exhibiting enhancement of migration (production LyMSF) rose to 39, 46% of cultures were inhibited (produced LyMIF) and 15% did not show any significant effect. Treatment of kidney recipients with ATG exerted strong inhibitory effect on the appearance of LyMSF and on the appearance of LyMIF in mixed cultures. These results suggested that LyMIF and LyMSF were produced by separate cell populations."} {"id": "PMID:155436", "title": "Steroids and immunosuppression. Effect on anastomotic intimal hyperplasia in femoral arterial dacron bypass grafts.", "content": "The effects of steroids and immunosuppression on 6-cm long bilateral femoral arterial Dacron bypass grafts were studied in 30 adult mongrel dogs. The dogs were serially placed into one of the following three groups: control, steroid, and immunosuppression. The control and steroid groups each had a 70% graft patency rate, whereas the immunosuppression group had a 100% eight-week graft patency rate. The results in the steroid group were not statistically different from the control group, whereas the results in the immunosuppression group were statistically different from the control. The decrease in internal diameter was secondary to a localized accumulation of tissue at the anastomotic site, which histologically appeared to be a hyperplastic intima morphologically different in each group. There is a substantial decrease in intimal hyperplasia at anastomotic sites and a higher graft patency rate in dogs treated with low-dose azathioprine as compared with control of steroid-treated animals. The mechanism seems to be a slower and more orderly intimalization rather than suppression of any specific intimal cellular elements.", "contents": "Steroids and immunosuppression. Effect on anastomotic intimal hyperplasia in femoral arterial dacron bypass grafts. The effects of steroids and immunosuppression on 6-cm long bilateral femoral arterial Dacron bypass grafts were studied in 30 adult mongrel dogs. The dogs were serially placed into one of the following three groups: control, steroid, and immunosuppression. The control and steroid groups each had a 70% graft patency rate, whereas the immunosuppression group had a 100% eight-week graft patency rate. The results in the steroid group were not statistically different from the control group, whereas the results in the immunosuppression group were statistically different from the control. The decrease in internal diameter was secondary to a localized accumulation of tissue at the anastomotic site, which histologically appeared to be a hyperplastic intima morphologically different in each group. There is a substantial decrease in intimal hyperplasia at anastomotic sites and a higher graft patency rate in dogs treated with low-dose azathioprine as compared with control of steroid-treated animals. The mechanism seems to be a slower and more orderly intimalization rather than suppression of any specific intimal cellular elements."} {"id": "PMID:155439", "title": "Axillo-axillary bypass for subclavian steal syndrome.", "content": "Since 1972, 14 patients with subclavian steal and four with primary vascular insufficiency of the arm have been operated on using the axillo-axillary bypass graft. Two grafts have been replaced, one after nine months for threatened erosion, and the other after three years for thrombosis due to disease progression in the donor artery. The new grafts were patent at three and at 2 1/2 years. One graft was occluded at six months and was not replaced. All other patients under observation in 1978 have grafts patent at one month to 6 1/2 years (average 2.2 years). Life table analysis shows the probability of graft patency (20 grafts) is 76% at three years. In the subclavian steal group steal on the left side predominated 2:1. Cerebral symptoms predominated with arm symptoms less often seen, although six patients had both. Associated vascular disease and hypertension were common. There was no mortality and few complications. Axillo-axillary bypass grafting is considered the operation of choice for patients with subclavian steal syndrome.", "contents": "Axillo-axillary bypass for subclavian steal syndrome. Since 1972, 14 patients with subclavian steal and four with primary vascular insufficiency of the arm have been operated on using the axillo-axillary bypass graft. Two grafts have been replaced, one after nine months for threatened erosion, and the other after three years for thrombosis due to disease progression in the donor artery. The new grafts were patent at three and at 2 1/2 years. One graft was occluded at six months and was not replaced. All other patients under observation in 1978 have grafts patent at one month to 6 1/2 years (average 2.2 years). Life table analysis shows the probability of graft patency (20 grafts) is 76% at three years. In the subclavian steal group steal on the left side predominated 2:1. Cerebral symptoms predominated with arm symptoms less often seen, although six patients had both. Associated vascular disease and hypertension were common. There was no mortality and few complications. Axillo-axillary bypass grafting is considered the operation of choice for patients with subclavian steal syndrome."} {"id": "PMID:155440", "title": "Suture material as a factor in the occurrence of anastomotic false aneurysms. An analysis of 26 cases.", "content": "False aneurysm formation is a well-recognized late complication of prosthetic graft insertion. Despite the fact that other etiologic factors may be involved, the behavior of the suture material remains of central importance. In a retrospective review of 1,330 peripheral vascular cases, we found 26 cases involving a total of 39 false aneurysms, or an incidence of 2% (26/1,330). Twenty-four of these were directly attributable to failure of the monofilament plastic suture or silk suture material. Braided Dacron suture was used in the original anastomosis in another seven cases, and in these instances the false aneurysms were not related to suture failure but were association with such factors as previous endarterectomy, failure of arterial wall, and chronic hypertension. None of the 39 aneurysms was secondary to infection or trauma. These results emphasize the importance of using a braided, nonabsorbable suture material to ensure the continued integrity of an anastomosis involving prosthetic grafts.", "contents": "Suture material as a factor in the occurrence of anastomotic false aneurysms. An analysis of 26 cases. False aneurysm formation is a well-recognized late complication of prosthetic graft insertion. Despite the fact that other etiologic factors may be involved, the behavior of the suture material remains of central importance. In a retrospective review of 1,330 peripheral vascular cases, we found 26 cases involving a total of 39 false aneurysms, or an incidence of 2% (26/1,330). Twenty-four of these were directly attributable to failure of the monofilament plastic suture or silk suture material. Braided Dacron suture was used in the original anastomosis in another seven cases, and in these instances the false aneurysms were not related to suture failure but were association with such factors as previous endarterectomy, failure of arterial wall, and chronic hypertension. None of the 39 aneurysms was secondary to infection or trauma. These results emphasize the importance of using a braided, nonabsorbable suture material to ensure the continued integrity of an anastomosis involving prosthetic grafts."} {"id": "PMID:155441", "title": "[Lengthwise splitting of myocardial cells and nuclei].", "content": "A possibility of a peculiar method for division of myocardial cells and nuclei--longitudinal splitting--has been studied in hypertrophic hearts of 19 corpses. Morphological examination of the myocardium (separate weighing of the cardiac ventricles, measuring of myocardial components and muscular fibres in microphotos of transversal sections) has not revealed any signs of longitudinal fibres splitting: their average thickness either increase or remain the same with growth of muscular mass, and per cent of thin and thick fibres remains within limits of unreliable fluctuations. Analysis of serial transversal sections of muscular fibres and their micrometry confirm the reality of longitudinal splitting of the nuclei which is realized through several steps and depends on the degree of hypertrophy of muscular fibres.", "contents": "[Lengthwise splitting of myocardial cells and nuclei]. A possibility of a peculiar method for division of myocardial cells and nuclei--longitudinal splitting--has been studied in hypertrophic hearts of 19 corpses. Morphological examination of the myocardium (separate weighing of the cardiac ventricles, measuring of myocardial components and muscular fibres in microphotos of transversal sections) has not revealed any signs of longitudinal fibres splitting: their average thickness either increase or remain the same with growth of muscular mass, and per cent of thin and thick fibres remains within limits of unreliable fluctuations. Analysis of serial transversal sections of muscular fibres and their micrometry confirm the reality of longitudinal splitting of the nuclei which is realized through several steps and depends on the degree of hypertrophy of muscular fibres."} {"id": "PMID:155442", "title": "[Alterations in the secretory glandulocytes of the stomach in the presence of an imbalance in adrenal cortex and thyroid gland hormones].", "content": "Gastric secretory granulocytes in Wistar rats were studied electron microscopically and microspectrophotometrically. Injection of L-thyroxin for 10--30 days resulted in decrease of acid phosphatase and ATPh-ase activity in the main and parietal granulocytes. Injection of hydrocortisone after or simultaneously with saturation of the organism with L-thyroxin results in increasing acid phosphatase activity of these cells. After simultaneous prolonged injection of these two hormones, the number of lysosomes increased in parietal glandulocytes and mitochondrial membranes were destroyed in the main and parietal glandulocytes. Together with these phenomena, changes in the activity of oxidative-reductive enzymes were observed, demonstrating a sharp decrease of energetic importance of the main oxidation way in Krebs cycle.", "contents": "[Alterations in the secretory glandulocytes of the stomach in the presence of an imbalance in adrenal cortex and thyroid gland hormones]. Gastric secretory granulocytes in Wistar rats were studied electron microscopically and microspectrophotometrically. Injection of L-thyroxin for 10--30 days resulted in decrease of acid phosphatase and ATPh-ase activity in the main and parietal granulocytes. Injection of hydrocortisone after or simultaneously with saturation of the organism with L-thyroxin results in increasing acid phosphatase activity of these cells. After simultaneous prolonged injection of these two hormones, the number of lysosomes increased in parietal glandulocytes and mitochondrial membranes were destroyed in the main and parietal glandulocytes. Together with these phenomena, changes in the activity of oxidative-reductive enzymes were observed, demonstrating a sharp decrease of energetic importance of the main oxidation way in Krebs cycle."} {"id": "PMID:155443", "title": "The improving hematologic picture in long-term surviving calves with total artificial hearts.", "content": "A coagulopathy associated with severe hemolysis was a limiting factor in obtaining long-term survivors among calves with total artificial hearts in 1969. Conversion of design from sac-type hearts to flexible diaphragm hearts, and from Silastic Dacron-fibril intimas to smooth polyurethane intimas, resulted in an abatement of the coagulopathy. In the most recent series of animals studied at this laboratory, platelet counts are normal and platelet survivals are half of normal. Plasma hemoglobins are normal. The coagulation system is still activated at specific loci within the total artificial heart, but is best compensated for in calves treated with antiplatelet drugs, having polyurethane hearts.", "contents": "The improving hematologic picture in long-term surviving calves with total artificial hearts. A coagulopathy associated with severe hemolysis was a limiting factor in obtaining long-term survivors among calves with total artificial hearts in 1969. Conversion of design from sac-type hearts to flexible diaphragm hearts, and from Silastic Dacron-fibril intimas to smooth polyurethane intimas, resulted in an abatement of the coagulopathy. In the most recent series of animals studied at this laboratory, platelet counts are normal and platelet survivals are half of normal. Plasma hemoglobins are normal. The coagulation system is still activated at specific loci within the total artificial heart, but is best compensated for in calves treated with antiplatelet drugs, having polyurethane hearts."} {"id": "PMID:155444", "title": "Interface radiation dosimetry in mandibular reconstruction.", "content": "When a beam of radiation crosses the interface between two substances, secondary electrons are generated. This results in enhancement of the absorbed dose of radiation roughly proportional to the difference in atomic numbers. Interfaces are created in reconstruction of the mandible with implantable trays containing hematopoietic bone marrow and cancellous bone chips. Radiation was measured in tissue-equivalent material surrounding mandibular tray implants of titanium, vitallium, stainless steel, and Dacron/polyetherurethane. The absorbed dose was enhanced by 29% to 36% adjacent to the metallic trays; 1% dose enhancement was noted adjacent to the Dacron/polyetherurethane tray. We conclude that, when radiation therapy is necessary following mandibular reconstruction, homogeneity of dose is maintained and local soft-tissue reactions to excessive irradiation may be avoided by using a nonmetallic tray.", "contents": "Interface radiation dosimetry in mandibular reconstruction. When a beam of radiation crosses the interface between two substances, secondary electrons are generated. This results in enhancement of the absorbed dose of radiation roughly proportional to the difference in atomic numbers. Interfaces are created in reconstruction of the mandible with implantable trays containing hematopoietic bone marrow and cancellous bone chips. Radiation was measured in tissue-equivalent material surrounding mandibular tray implants of titanium, vitallium, stainless steel, and Dacron/polyetherurethane. The absorbed dose was enhanced by 29% to 36% adjacent to the metallic trays; 1% dose enhancement was noted adjacent to the Dacron/polyetherurethane tray. We conclude that, when radiation therapy is necessary following mandibular reconstruction, homogeneity of dose is maintained and local soft-tissue reactions to excessive irradiation may be avoided by using a nonmetallic tray."} {"id": "PMID:155446", "title": "Stenotic conditions of the lumbar spinal canal: changes in surgical techniques in the management of low back disability.", "content": "The diagnostic recognition of acquired stenotic conditions in the lumbar spinal canal occurring from the fifth to the eighth decades of life had led to a significant change in surgical techniques during the last ten years. This communication presents a comparison of surgical techniques used by the author in two consecutive series of patients operated for low back, lumbosciatic, and spondylotic caudal disability syndromes during the period 1965 to 1969 inclusive (100 patients) and 1976 and 1977 (105 patients). Interlaminar discectomy was carried out in 88%, and laminectomy with spinal nerve nerolysis in 12%, of the 1965 - 1969 series. Discectomy by interlaminar approach was carried out in only 10% of the 1976 - 1977 series; all other patients had laminectomies with or without discectomies. Early follow-up results in the recent series indicate a significant (20%) increase in the number of patients who resumed their previous occupations as compared with those in the previous series.", "contents": "Stenotic conditions of the lumbar spinal canal: changes in surgical techniques in the management of low back disability. The diagnostic recognition of acquired stenotic conditions in the lumbar spinal canal occurring from the fifth to the eighth decades of life had led to a significant change in surgical techniques during the last ten years. This communication presents a comparison of surgical techniques used by the author in two consecutive series of patients operated for low back, lumbosciatic, and spondylotic caudal disability syndromes during the period 1965 to 1969 inclusive (100 patients) and 1976 and 1977 (105 patients). Interlaminar discectomy was carried out in 88%, and laminectomy with spinal nerve nerolysis in 12%, of the 1965 - 1969 series. Discectomy by interlaminar approach was carried out in only 10% of the 1976 - 1977 series; all other patients had laminectomies with or without discectomies. Early follow-up results in the recent series indicate a significant (20%) increase in the number of patients who resumed their previous occupations as compared with those in the previous series."} {"id": "PMID:155452", "title": "Effect of chronic ethanol administration on energy metabolism and phospholipase A2 activity in rat liver.", "content": "1. For a period of 31 days male rats were given a liquid diet containing 36% of its energy as ethanol. Liver mitochondria from these animals demonstrated lowered respiratory control with succinate as substrate, a diminished energy-linked anilinonaphthalene-sulphonic acid fluorescence response, and lowered endogenous ATP concentrations. The phospholipid/protein ratio in mitochondria from these animals was unchanged; only minor alterations in the phospholipid fatty acid composition were observed. 2. In experiments where mitochondria were incubated at 18 degrees C in iso-osmotic sucrose (aging experiments), the above energy-linked properties were lost at an earlier time in organelles from ethanol-fed animals. Phospholipase A2 acitivty was depressed in mitochondria from control animals until respiratory control was lost and ATP was depleted. In contrast, no lag in the expression of phospholipase activity was observed in mitochondria from ethanol-fed rats. This loss of control of the phospholipase resulted in an earlier degradation of membrane phospholipids under the conditions of the aging experiments. 3. The ATPase (adenosine triphosphatase) activities, measured in freshly prepared tightly coupled mitochondria and in organelles uncoupled with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, were not significantly different in ethanol-fed and liquid-diet control animals. When the mitochondria were aged at 18 degrees C, the activity increased with time of incubation in organelles from both groups of animals. A lag was observed, however, as the ATPase activity increased in control preparations. This lag was not present as APTase activity increased in mitochondria from ethanol-fed animals. 4. The significantly lowered values observed for energy-linked functions with succinate as an energy source demonstrate that ethanol elicits an alteration in liver mitochondria that affects the site II-site III regions of the oxidative-phosphorylation system. The apparent lack of control of the phospholipase A2 and ATPase activities in mitochondria from ethanol-fed animals suggests that the membrane microenvironment of these enzymes has been altered such that they can exert their catabolic effects more readily under conditions of mild perturbation. The fatty acid analyses demonstrate that the observed alterations both in the energy-linked functions and in control of the phospholipase and ATPase are not mediated through changes in the acyl chain composition of bulk-phase phospholipids.", "contents": "Effect of chronic ethanol administration on energy metabolism and phospholipase A2 activity in rat liver. 1. For a period of 31 days male rats were given a liquid diet containing 36% of its energy as ethanol. Liver mitochondria from these animals demonstrated lowered respiratory control with succinate as substrate, a diminished energy-linked anilinonaphthalene-sulphonic acid fluorescence response, and lowered endogenous ATP concentrations. The phospholipid/protein ratio in mitochondria from these animals was unchanged; only minor alterations in the phospholipid fatty acid composition were observed. 2. In experiments where mitochondria were incubated at 18 degrees C in iso-osmotic sucrose (aging experiments), the above energy-linked properties were lost at an earlier time in organelles from ethanol-fed animals. Phospholipase A2 acitivty was depressed in mitochondria from control animals until respiratory control was lost and ATP was depleted. In contrast, no lag in the expression of phospholipase activity was observed in mitochondria from ethanol-fed rats. This loss of control of the phospholipase resulted in an earlier degradation of membrane phospholipids under the conditions of the aging experiments. 3. The ATPase (adenosine triphosphatase) activities, measured in freshly prepared tightly coupled mitochondria and in organelles uncoupled with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, were not significantly different in ethanol-fed and liquid-diet control animals. When the mitochondria were aged at 18 degrees C, the activity increased with time of incubation in organelles from both groups of animals. A lag was observed, however, as the ATPase activity increased in control preparations. This lag was not present as APTase activity increased in mitochondria from ethanol-fed animals. 4. The significantly lowered values observed for energy-linked functions with succinate as an energy source demonstrate that ethanol elicits an alteration in liver mitochondria that affects the site II-site III regions of the oxidative-phosphorylation system. The apparent lack of control of the phospholipase A2 and ATPase activities in mitochondria from ethanol-fed animals suggests that the membrane microenvironment of these enzymes has been altered such that they can exert their catabolic effects more readily under conditions of mild perturbation. The fatty acid analyses demonstrate that the observed alterations both in the energy-linked functions and in control of the phospholipase and ATPase are not mediated through changes in the acyl chain composition of bulk-phase phospholipids."} {"id": "PMID:155456", "title": "Substrate cycles: their metabolic, energetic and thermic consequences in man.", "content": "The role of substrate cycles in metabolic control was first indicated over ten years ago, but the recent interest in such cycles has developed from the direct demonstration by isotopic techniques of their existence in various tissues. I propose that substrate cycles form part of a logical series of biochemical mechanisms that exist to increase the sensitivity of non-equilibrium reactions to changes in concentrations of metabolic regulators. The possible importance of such cycles for provision of precise metabolic regulation in the tissues of the normal subject and the trained athlete is proposed. Furthermore, cycling may provide a mechanism by which hormones can change the magnitude of response in a tissue to a given metabolic signal, without interfering in the biochemistry of the basic control mechanism. It is, however, possible to extend the role of cycling to heat generation and thus to controlled energy loss by an organism. Heat generation by substrate cycles may be important as an acute mechanism for maintaining the body temperature in man in response to a sudden decrease in the environmental temperature; alcoholic hypothermia would be explained by inhibition of substrate cycling in the liver, and accidental hypothermia in the elderly could be explained by decreased capacity of substrate cycles with age. If heat generated by the cycles is rapidly lost to the environment, the expenditure of energy to maintain this heat loss could explain, in part, the physiological phenomena of the thermic response to food and the oxygen debt which is always observed after exercise. Finally, the energy expended in these ways could be part of a general biochemical mechanism for maintenance of the correct body weight; a decrease in the capacity of substrate cycles might be one factor involved in the development of obesity.", "contents": "Substrate cycles: their metabolic, energetic and thermic consequences in man. The role of substrate cycles in metabolic control was first indicated over ten years ago, but the recent interest in such cycles has developed from the direct demonstration by isotopic techniques of their existence in various tissues. I propose that substrate cycles form part of a logical series of biochemical mechanisms that exist to increase the sensitivity of non-equilibrium reactions to changes in concentrations of metabolic regulators. The possible importance of such cycles for provision of precise metabolic regulation in the tissues of the normal subject and the trained athlete is proposed. Furthermore, cycling may provide a mechanism by which hormones can change the magnitude of response in a tissue to a given metabolic signal, without interfering in the biochemistry of the basic control mechanism. It is, however, possible to extend the role of cycling to heat generation and thus to controlled energy loss by an organism. Heat generation by substrate cycles may be important as an acute mechanism for maintaining the body temperature in man in response to a sudden decrease in the environmental temperature; alcoholic hypothermia would be explained by inhibition of substrate cycling in the liver, and accidental hypothermia in the elderly could be explained by decreased capacity of substrate cycles with age. If heat generated by the cycles is rapidly lost to the environment, the expenditure of energy to maintain this heat loss could explain, in part, the physiological phenomena of the thermic response to food and the oxygen debt which is always observed after exercise. Finally, the energy expended in these ways could be part of a general biochemical mechanism for maintenance of the correct body weight; a decrease in the capacity of substrate cycles might be one factor involved in the development of obesity."} {"id": "PMID:155457", "title": "[Studies on the biotransformation of fominoben-HCl in man (author's transl)].", "content": "The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively.", "contents": "[Studies on the biotransformation of fominoben-HCl in man (author's transl)]. The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively."} {"id": "PMID:155459", "title": "[The effect of fominoben and oxyethyltheophylline in combination on pulmonary function and pulmonary hemodynamics in chronic-obstructive diseases of the airways (author's transl)].", "content": "Mechanics of breathing, gas exchange and pulmonary hemodynamics were investigated in 10 patients with chronic-obstructive lung diseases before and after treatment with oral doses of 160 mg 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)benzanilide hydrochloride (fominoben, Noleptan) and 300 mg oxyethyltheophylline given three times daily. The data of lung function showed a slight decrease of airway obstruction during the treatment. Hyperinflation of the lung, restriction, gas exchange were not significantly changed on the average. The main effect was an improvement of pulmonary hemodynamics: the pathologically increased mean pressures in the pulmonary artery were normalized after treatment.", "contents": "[The effect of fominoben and oxyethyltheophylline in combination on pulmonary function and pulmonary hemodynamics in chronic-obstructive diseases of the airways (author's transl)]. Mechanics of breathing, gas exchange and pulmonary hemodynamics were investigated in 10 patients with chronic-obstructive lung diseases before and after treatment with oral doses of 160 mg 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)benzanilide hydrochloride (fominoben, Noleptan) and 300 mg oxyethyltheophylline given three times daily. The data of lung function showed a slight decrease of airway obstruction during the treatment. Hyperinflation of the lung, restriction, gas exchange were not significantly changed on the average. The main effect was an improvement of pulmonary hemodynamics: the pathologically increased mean pressures in the pulmonary artery were normalized after treatment."} {"id": "PMID:155460", "title": "Studies on the sympathomimetic effects of guanoxan on smooth muscles of rat.", "content": "In anococcygeus muscle and vas deferens preparations of rat, guanidinomethyl-2-benzo-(1,4)-dioxane (guanoxan) potentiated responses to norepinephrine (NF) in concentrations which exerted a neurone blocking effect. The potentiation was significantly reduced in reserpinized preparations and was abolished in the presence of nialamide. The possible mechanisms of potentiation have been discussed. Higher concentrations of guanoxan produced concentration-related contractions. The contractions were significantly less in reserpinized preparations. Phentolamine both prevented and reversed the contractions while methysergide was ineffective in this respect. Thus the effect of guanoxan appears to be mediated through the activation of alpha-receptors by the released NE.", "contents": "Studies on the sympathomimetic effects of guanoxan on smooth muscles of rat. In anococcygeus muscle and vas deferens preparations of rat, guanidinomethyl-2-benzo-(1,4)-dioxane (guanoxan) potentiated responses to norepinephrine (NF) in concentrations which exerted a neurone blocking effect. The potentiation was significantly reduced in reserpinized preparations and was abolished in the presence of nialamide. The possible mechanisms of potentiation have been discussed. Higher concentrations of guanoxan produced concentration-related contractions. The contractions were significantly less in reserpinized preparations. Phentolamine both prevented and reversed the contractions while methysergide was ineffective in this respect. Thus the effect of guanoxan appears to be mediated through the activation of alpha-receptors by the released NE."} {"id": "PMID:155466", "title": "Performance of a shell-type heat exchanger in extracorporeal circulation.", "content": "Tests were performed on a \"shell\" type heat exchanger used in a simulated extracorporeal circulation. The counter flow mode was the most efficient pattern and recommendations are made on which flow pattern should be employed with low water flow rates.", "contents": "Performance of a shell-type heat exchanger in extracorporeal circulation. Tests were performed on a \"shell\" type heat exchanger used in a simulated extracorporeal circulation. The counter flow mode was the most efficient pattern and recommendations are made on which flow pattern should be employed with low water flow rates."} {"id": "PMID:155468", "title": "The effect of vitamin A acid on experimentally induced comedones: an electron microscope study.", "content": "Various concentrations of vitamin A acid were applied to experimentally induced comedones. All concentrations produced non-cohesive hyperkeratinization, which loosened the cohesive horny mass induced by oleic acid and expelled it from the follicle within 7 days. The highest concentration (0.1%) produced the greatest degree of non-cohesive desquamation in the shortest time. In follicles treated with the acid, the cell membrane of horny cells was thin and ruptured easily to produce a non-cohesive debris. Desmosomes were scarce and desmosomal bodies (fusiform electron-dense bodies) and tight junctions between horny cells were not seen in follicles treated with the acid. The acid also produced hyperplasia of the epithelial wall and an apparently increased mitotic rate. A 0.025% concentration of the acid increased the number of membrane coating granules by about 70% in all regions of the follicle.", "contents": "The effect of vitamin A acid on experimentally induced comedones: an electron microscope study. Various concentrations of vitamin A acid were applied to experimentally induced comedones. All concentrations produced non-cohesive hyperkeratinization, which loosened the cohesive horny mass induced by oleic acid and expelled it from the follicle within 7 days. The highest concentration (0.1%) produced the greatest degree of non-cohesive desquamation in the shortest time. In follicles treated with the acid, the cell membrane of horny cells was thin and ruptured easily to produce a non-cohesive debris. Desmosomes were scarce and desmosomal bodies (fusiform electron-dense bodies) and tight junctions between horny cells were not seen in follicles treated with the acid. The acid also produced hyperplasia of the epithelial wall and an apparently increased mitotic rate. A 0.025% concentration of the acid increased the number of membrane coating granules by about 70% in all regions of the follicle."} {"id": "PMID:155469", "title": "Mandibular reconstruction and craniofacial fairing.", "content": "A method of restoring bony contour defects in the craniofacial regions employing a combination graft of autogenous bone and an alloplastic mesh is presented. Osteoinduction occurs within the confines of the alloplastic mesh from the cancellous bone and the resultant new bone conforms to the outline imposed by the alloplastic device. The advantages of this method include those of alloplastic materials combined with those of bone grafting. There is immediate restoration of an aesthetic contour with adequate strength and sound fixation.", "contents": "Mandibular reconstruction and craniofacial fairing. A method of restoring bony contour defects in the craniofacial regions employing a combination graft of autogenous bone and an alloplastic mesh is presented. Osteoinduction occurs within the confines of the alloplastic mesh from the cancellous bone and the resultant new bone conforms to the outline imposed by the alloplastic device. The advantages of this method include those of alloplastic materials combined with those of bone grafting. There is immediate restoration of an aesthetic contour with adequate strength and sound fixation."} {"id": "PMID:155470", "title": "Physical properties of myosin from aortic smooth muscle.", "content": "Porcine aortic myosin is a smooth muscle contractile protein similar to its striated muscle counterpart. Electrophoresis in sodium dodecyl sulfate indicates that the molecule consists of three classes of subunits with polypeptide chain molecular weights of 192,000, 19,000, and 15,000. At 277 nm the absorption spectrum gives an extinction coefficient for aortic myosin of 0.558 cm2/mg; the circular dichroism spectrum of the protein indicates that aortic myosin contains about 70% of its residues in the alpha-helical configuration. Amino acid analysis shows that the smooth muscle myosin has significantly more arginine and leucine and significantly less valine and isoleucine than rabbit skeletal muscle myosin. Other studies yielded these data: Vapp = 0.716 mL/g [eta] = 0.213 mL/mg, S20, w = 5.84 x 10(-13)S. Similar studies with rabbit skeletal muscle myosin indicate that Vapp = 0.711 mL/g and S20, w = 6.36 x 10(-13)S. These properties suggest that aortic myosin, like skeletal muscle myosin, behaves hydrodynamically like a rigid rod.", "contents": "Physical properties of myosin from aortic smooth muscle. Porcine aortic myosin is a smooth muscle contractile protein similar to its striated muscle counterpart. Electrophoresis in sodium dodecyl sulfate indicates that the molecule consists of three classes of subunits with polypeptide chain molecular weights of 192,000, 19,000, and 15,000. At 277 nm the absorption spectrum gives an extinction coefficient for aortic myosin of 0.558 cm2/mg; the circular dichroism spectrum of the protein indicates that aortic myosin contains about 70% of its residues in the alpha-helical configuration. Amino acid analysis shows that the smooth muscle myosin has significantly more arginine and leucine and significantly less valine and isoleucine than rabbit skeletal muscle myosin. Other studies yielded these data: Vapp = 0.716 mL/g [eta] = 0.213 mL/mg, S20, w = 5.84 x 10(-13)S. Similar studies with rabbit skeletal muscle myosin indicate that Vapp = 0.711 mL/g and S20, w = 6.36 x 10(-13)S. These properties suggest that aortic myosin, like skeletal muscle myosin, behaves hydrodynamically like a rigid rod."} {"id": "PMID:155473", "title": "Neutral protease inhibitors from human intervertebral disc and femoral head articular cartilage.", "content": "Assays of several proteases, incorporating guanidinium chloride extracts of human femoral head cartilage and intervertebral disc, demonstrated that both tissues contain inhibitors of certain serine proteases. Trypsin, chymotrypsin and a granule extract of human polymorphonuclear leukocytes containing elastase and cathepsin G activities, were inhibited by low molecular weight fractions prepared by Sephadex G-75 chromatography. Using a radioassay, it was further shown that these fractions inhibit proteolysis of cartilage proteoglycan. The inhibitor in intervertebral disc is concentrated in the nucleus pulposus, with a decreasing gradient to the periphery of the annulus fibrosus. It is proposed that these inhibitors confer at least partial protection against pathological proteolysis of the proteoglycans in human articular cartilage and nucleus pulposus.", "contents": "Neutral protease inhibitors from human intervertebral disc and femoral head articular cartilage. Assays of several proteases, incorporating guanidinium chloride extracts of human femoral head cartilage and intervertebral disc, demonstrated that both tissues contain inhibitors of certain serine proteases. Trypsin, chymotrypsin and a granule extract of human polymorphonuclear leukocytes containing elastase and cathepsin G activities, were inhibited by low molecular weight fractions prepared by Sephadex G-75 chromatography. Using a radioassay, it was further shown that these fractions inhibit proteolysis of cartilage proteoglycan. The inhibitor in intervertebral disc is concentrated in the nucleus pulposus, with a decreasing gradient to the periphery of the annulus fibrosus. It is proposed that these inhibitors confer at least partial protection against pathological proteolysis of the proteoglycans in human articular cartilage and nucleus pulposus."} {"id": "PMID:155475", "title": "[Investigation of sarcoplasmic reticulum SH-groups].", "content": "The amount and the reaction capacity of the thiol groups in the sarcoplasmic reticulum containing up to 86% of Ca-ATPase were determined using 7-chloro-4-nitrobenzo-2-hydroxo-1,3-diazole (NBD-chloride). The total amount of SH-groups interacting with NBD-chloride is about 9 moles/10(5) g of protein as determined in the excess of NBD-chloride (750 micrometers). With respect to their sensitivity to NBD-chloride the SH-groups may be divided into two classes: slow and fast ones (5,3 and 3,5 moles/10(5) g of protein, respectively). The modification constants for the fast and slow SH-groups are 0,16 and 0,015min-1. ATP (30 micrometers) decreases the number of fast groups by 1 mole/10(5) g of protein. At higher concentrations of ATP (1--3 mM) the amount of fast SH-groups is decreased by 3 moles/10(5) g of protein, their modification rate constant being decreased 2-fold. ATP at concentration of 1 mM, decreases the rate constant for the Ca-ATPase inactivation by NBD-chloride from 0.68 down to 0,073 min-1, which coincides with the modification rate constant for fast SH-groups (0,071 min-1) under the same conditions. Ca2+ at concentration of 10(-4) M increases the amount of fast thiol groups by 1 mole/10(5) g of protein, the rate constant of their modification by NBD-chloride being increased 2-fold. A half-maximal effect was observed in the presence of 5.10(-7) M Ca2+ . Mg2+ did not affect the total amount of fast thiol groups; however, it decreased their modification rate constant.", "contents": "[Investigation of sarcoplasmic reticulum SH-groups]. The amount and the reaction capacity of the thiol groups in the sarcoplasmic reticulum containing up to 86% of Ca-ATPase were determined using 7-chloro-4-nitrobenzo-2-hydroxo-1,3-diazole (NBD-chloride). The total amount of SH-groups interacting with NBD-chloride is about 9 moles/10(5) g of protein as determined in the excess of NBD-chloride (750 micrometers). With respect to their sensitivity to NBD-chloride the SH-groups may be divided into two classes: slow and fast ones (5,3 and 3,5 moles/10(5) g of protein, respectively). The modification constants for the fast and slow SH-groups are 0,16 and 0,015min-1. ATP (30 micrometers) decreases the number of fast groups by 1 mole/10(5) g of protein. At higher concentrations of ATP (1--3 mM) the amount of fast SH-groups is decreased by 3 moles/10(5) g of protein, their modification rate constant being decreased 2-fold. ATP at concentration of 1 mM, decreases the rate constant for the Ca-ATPase inactivation by NBD-chloride from 0.68 down to 0,073 min-1, which coincides with the modification rate constant for fast SH-groups (0,071 min-1) under the same conditions. Ca2+ at concentration of 10(-4) M increases the amount of fast thiol groups by 1 mole/10(5) g of protein, the rate constant of their modification by NBD-chloride being increased 2-fold. A half-maximal effect was observed in the presence of 5.10(-7) M Ca2+ . Mg2+ did not affect the total amount of fast thiol groups; however, it decreased their modification rate constant."} {"id": "PMID:155476", "title": "[Effect of nitrate and cytokinin on nitrate reductase activity in isolated corncockle embryos].", "content": "The effects of cytokinin and nitrate on the activity of nitrate reductase (NR) in isolated embryos of Agrostemma githago L. were studied. It was shown that the effects of cytokinin and NO-3 on the induction of NR is additive during 8, 12 and 18 hrs of embryos incubation in the solutions of the two inducers. Anticytokinin decreased the cytokinin induced NR by 35--39% and had no effect on the NR induction by nitrate. The substrate and hormonal induction of NR differed in the duration of the lag period. This difference dependent on the physiological state of the embryos at the beginning of incubation. The data obtained are indicative of the independence of cytokinin and NO-3 effects on the NR synthesis in isolated embryos of Agrostemma githago L. Abscisic acid supressed cytokinin- and nitrate-induced NR and had practically no effect on total incorporation of the label into the protein. It is assumed that the induced synthesis of the protein is more sensitive to the action of abscisic acid that the total protein synthesis.", "contents": "[Effect of nitrate and cytokinin on nitrate reductase activity in isolated corncockle embryos]. The effects of cytokinin and nitrate on the activity of nitrate reductase (NR) in isolated embryos of Agrostemma githago L. were studied. It was shown that the effects of cytokinin and NO-3 on the induction of NR is additive during 8, 12 and 18 hrs of embryos incubation in the solutions of the two inducers. Anticytokinin decreased the cytokinin induced NR by 35--39% and had no effect on the NR induction by nitrate. The substrate and hormonal induction of NR differed in the duration of the lag period. This difference dependent on the physiological state of the embryos at the beginning of incubation. The data obtained are indicative of the independence of cytokinin and NO-3 effects on the NR synthesis in isolated embryos of Agrostemma githago L. Abscisic acid supressed cytokinin- and nitrate-induced NR and had practically no effect on total incorporation of the label into the protein. It is assumed that the induced synthesis of the protein is more sensitive to the action of abscisic acid that the total protein synthesis."} {"id": "PMID:155478", "title": "[Regeneration of electrical activity in anterior abdominal wall muscles following prolonged atrophy].", "content": "A possibility of restoration of the functional condition of the anterior abdominal wall muscles was demonstrated by the electrical activity parameters following long-term atrophy caused by a giant ventral hernia. Restoration of electromyographic indices was more complete when the anterior abdominal wall was stabilized with synthetic prosthesis material, since the muscle fibers in this case failed to be involved in the suture and were in functionally advantageous position.", "contents": "[Regeneration of electrical activity in anterior abdominal wall muscles following prolonged atrophy]. A possibility of restoration of the functional condition of the anterior abdominal wall muscles was demonstrated by the electrical activity parameters following long-term atrophy caused by a giant ventral hernia. Restoration of electromyographic indices was more complete when the anterior abdominal wall was stabilized with synthetic prosthesis material, since the muscle fibers in this case failed to be involved in the suture and were in functionally advantageous position."} {"id": "PMID:155474", "title": "[Complex biochemical and structural study of skeletal muscles in scoliosis].", "content": "Structural study of human scoliosis muscles showed significant dystrophic and degenerative changes: desintegration of fibrillar structure and striation; the Zencker necrosis; the replacement of muscular tissue by connective and adipose tissues. The electron microscopic observation revealed disordering of filamental array of the sarcomere (I- and A-discs), the broadening of Z-disc material, the appearance of N-stripes in I-band. At the same time deviations from the norm were observed in contractile proteins: actin and myosin. ATPase activity of myosin decreased by 25--30%; the flow of birefringence of myosin and especially of actin also decreased. Actin from the scoliosis muscles partially or completely lost the ability for polymerization in 0.1 M KC1.", "contents": "[Complex biochemical and structural study of skeletal muscles in scoliosis]. Structural study of human scoliosis muscles showed significant dystrophic and degenerative changes: desintegration of fibrillar structure and striation; the Zencker necrosis; the replacement of muscular tissue by connective and adipose tissues. The electron microscopic observation revealed disordering of filamental array of the sarcomere (I- and A-discs), the broadening of Z-disc material, the appearance of N-stripes in I-band. At the same time deviations from the norm were observed in contractile proteins: actin and myosin. ATPase activity of myosin decreased by 25--30%; the flow of birefringence of myosin and especially of actin also decreased. Actin from the scoliosis muscles partially or completely lost the ability for polymerization in 0.1 M KC1."} {"id": "PMID:155479", "title": "[Analysis of the effect of phenamine, L-DOPA and parachlorophenylalanine on the zoo-social behavior of isolated mice].", "content": "Abnormal changes in the structure of the individual and zoo-social behaviour of isolated mice due to phenamine (amphethamine), L-DOPA or PCPA were shown. Several elements of the \"pathological syndrome of isolation\" in mice were found to increase under the action of the drugs studied. The extension or reduction of contacts between animals of the same species was used as an integrative indicator of recovering (resocializing) or aggravating (desocializing) effect of psychotropic drugs on the pathology of animal behaviour.", "contents": "[Analysis of the effect of phenamine, L-DOPA and parachlorophenylalanine on the zoo-social behavior of isolated mice]. Abnormal changes in the structure of the individual and zoo-social behaviour of isolated mice due to phenamine (amphethamine), L-DOPA or PCPA were shown. Several elements of the \"pathological syndrome of isolation\" in mice were found to increase under the action of the drugs studied. The extension or reduction of contacts between animals of the same species was used as an integrative indicator of recovering (resocializing) or aggravating (desocializing) effect of psychotropic drugs on the pathology of animal behaviour."} {"id": "PMID:155480", "title": "[Nature of the suppressor cells blocking the activation of DNA synthesis in mixed cultures of normal lymphocytes].", "content": "The nature of suppressor cells which are contained in lymphocyte suspension of mice immunized with allogeneic tumor cells and inhibit the DNA synthesis activation in mixed normal lymphocyte cultures has been studied. The suppressor cells are shown to be resistant to mitomycin C, X-irradiation and are not inactivated by the treatment of anti-O-serum or anti-Ig-serum in the presence of the complement. They adhere to the plastic and are inactivated by carrageenan in vitro. The macrophage nature of the suppressor cells is suggested.", "contents": "[Nature of the suppressor cells blocking the activation of DNA synthesis in mixed cultures of normal lymphocytes]. The nature of suppressor cells which are contained in lymphocyte suspension of mice immunized with allogeneic tumor cells and inhibit the DNA synthesis activation in mixed normal lymphocyte cultures has been studied. The suppressor cells are shown to be resistant to mitomycin C, X-irradiation and are not inactivated by the treatment of anti-O-serum or anti-Ig-serum in the presence of the complement. They adhere to the plastic and are inactivated by carrageenan in vitro. The macrophage nature of the suppressor cells is suggested."} {"id": "PMID:155481", "title": "[Changes in the level of epidermal G2-chalone and mitotic activity in the rat vaginal epithelium].", "content": "The content of tissue-specific inhibitor of mitosis in epidermal epithelium (G2-chalone) was estimated by a single radial immunodiffusion test in the rat vagina during various stages of the estrous cycle. The level of chalone was found to correlate with the mitotic index (MI) of vaginal epithelium. The lowest level of G2-chalone is detected in proestrus and the highest one in estrus. The level of G2-chalone in vaginal epithelium was shown to be significantly decreased in aging rats (14--16 month-old) with regular cycles as compared to that in young normal cycle rats (3--4 month-old). The single injection of estradiol benzoate (1 microgram/100 g) into ovariectomized rats led to an increase in the MI following 18 hours. The increased MI is preceeded by a substantial drop of the G2-chalone level 12 hours after estrogen injection.", "contents": "[Changes in the level of epidermal G2-chalone and mitotic activity in the rat vaginal epithelium]. The content of tissue-specific inhibitor of mitosis in epidermal epithelium (G2-chalone) was estimated by a single radial immunodiffusion test in the rat vagina during various stages of the estrous cycle. The level of chalone was found to correlate with the mitotic index (MI) of vaginal epithelium. The lowest level of G2-chalone is detected in proestrus and the highest one in estrus. The level of G2-chalone in vaginal epithelium was shown to be significantly decreased in aging rats (14--16 month-old) with regular cycles as compared to that in young normal cycle rats (3--4 month-old). The single injection of estradiol benzoate (1 microgram/100 g) into ovariectomized rats led to an increase in the MI following 18 hours. The increased MI is preceeded by a substantial drop of the G2-chalone level 12 hours after estrogen injection."} {"id": "PMID:155493", "title": "Effect of mithramycin on bone beta-glucuronidase and resorption.", "content": "Mithramycin suppresses bone resorption. Its effect on the synthesis and release of beta-glucuronidase (a referent for lysosomal enzymes) in mouse calvarial explants was studied in an in vitro culture system. A newly described medium (designated as KT medium) was introduced in this specific study. Mithramycin initially inhibited the release of beta-glucuronidase into the medium and resulted in an ultimate accumulation of this enzyme in the bone. These results suggest that inhibition of bone resorption by mithramycin may be attributed to interference in release of lysosomal enzymes from bone cells.", "contents": "Effect of mithramycin on bone beta-glucuronidase and resorption. Mithramycin suppresses bone resorption. Its effect on the synthesis and release of beta-glucuronidase (a referent for lysosomal enzymes) in mouse calvarial explants was studied in an in vitro culture system. A newly described medium (designated as KT medium) was introduced in this specific study. Mithramycin initially inhibited the release of beta-glucuronidase into the medium and resulted in an ultimate accumulation of this enzyme in the bone. These results suggest that inhibition of bone resorption by mithramycin may be attributed to interference in release of lysosomal enzymes from bone cells."} {"id": "PMID:155495", "title": "Thermal injury to the bowel as a complication of laparoscopic sterilization.", "content": "Thermal injury to the small bowel occurred four times in a series of 7466 consecutive laparoscopies and tubal cauterization performed for sterilization. The four patients presented with signs and symptoms of delayed bowel perforation 4 to 11 days after the procedure. The perforations were small and involved the antimesenteric border of the terminal ileum. Histologic study of the excised specimen in one case showed full thickness coagulative necrosis of the bowel wall. Potential causes for bowel burn associated with tubal cauterization are discussed. Steps to minimize the occurrence of this complication include proper use of the laparoscope and cautery equipment, good anesthesia and gas distension of the abdomen, correct positioning of the patient and clear visualization of the operative field.", "contents": "Thermal injury to the bowel as a complication of laparoscopic sterilization. Thermal injury to the small bowel occurred four times in a series of 7466 consecutive laparoscopies and tubal cauterization performed for sterilization. The four patients presented with signs and symptoms of delayed bowel perforation 4 to 11 days after the procedure. The perforations were small and involved the antimesenteric border of the terminal ileum. Histologic study of the excised specimen in one case showed full thickness coagulative necrosis of the bowel wall. Potential causes for bowel burn associated with tubal cauterization are discussed. Steps to minimize the occurrence of this complication include proper use of the laparoscope and cautery equipment, good anesthesia and gas distension of the abdomen, correct positioning of the patient and clear visualization of the operative field."} {"id": "PMID:155497", "title": "Legal opinion on position paper: withholding treatment.", "content": "We have reviewed carefully the position paper and wish to provide the Association with our opinion with respect to the legal implications involved. This is one paper which clearly supports the \"right to life\" of newly born retarded or mentally defective infants. In our opinion, this position is entirely within the law. However, the paper does raise a number of significant legal questions which we believe warrant consideration. It is our respectful opinion that a physician, when faced with a situation of parental choice to withhold treatment, should seek the guidance of the Court and only withhold treatment or administer treatment with the back-up of a Court order.", "contents": "Legal opinion on position paper: withholding treatment. We have reviewed carefully the position paper and wish to provide the Association with our opinion with respect to the legal implications involved. This is one paper which clearly supports the \"right to life\" of newly born retarded or mentally defective infants. In our opinion, this position is entirely within the law. However, the paper does raise a number of significant legal questions which we believe warrant consideration. It is our respectful opinion that a physician, when faced with a situation of parental choice to withhold treatment, should seek the guidance of the Court and only withhold treatment or administer treatment with the back-up of a Court order."} {"id": "PMID:155498", "title": "Left ventricular hypertrophy and its reversibility in young spontaneously hypertensive rats.", "content": "The development of an increased ventricular wall mass was followed from birth until five weeks of age and also later in life in spontaneously hypertensive rats (SHR) which were compared with normotensive control rats (NCR). It was shown that the first signs of enhanced ventricular growth were already evident in SHR in the first week of life. At 10 months of age left ventricular weight was 68% higher in SHR than in matched NCR, at a mean pressure difference of 30%. Treatment of SHR with antihypertensive agents, like hydralazine, hydralazine-guanethidine, propranolol, or metoprolol, from three weeks up to 10 months of age reduced this gross increase in left ventricular weight by only about 10% while the mean pressure difference between SHR and NCR was reduced by 50 to 70%. It appears that the increase in left ventricular wall mass in SHR is initiated so early in life and is of such a character that it can only, to a fairly minor extent, be reversed or prevented by pressure-lowering procedures. Part of the explanation may be a substantial contribution of myocardial hyperplasia, in association with a genetically linked predisposal to structural cardiovascular adaptation, either 'inherent' in the effectors and/or caused by 'trophic' influences of a hormonal and/or transmitter nature.", "contents": "Left ventricular hypertrophy and its reversibility in young spontaneously hypertensive rats. The development of an increased ventricular wall mass was followed from birth until five weeks of age and also later in life in spontaneously hypertensive rats (SHR) which were compared with normotensive control rats (NCR). It was shown that the first signs of enhanced ventricular growth were already evident in SHR in the first week of life. At 10 months of age left ventricular weight was 68% higher in SHR than in matched NCR, at a mean pressure difference of 30%. Treatment of SHR with antihypertensive agents, like hydralazine, hydralazine-guanethidine, propranolol, or metoprolol, from three weeks up to 10 months of age reduced this gross increase in left ventricular weight by only about 10% while the mean pressure difference between SHR and NCR was reduced by 50 to 70%. It appears that the increase in left ventricular wall mass in SHR is initiated so early in life and is of such a character that it can only, to a fairly minor extent, be reversed or prevented by pressure-lowering procedures. Part of the explanation may be a substantial contribution of myocardial hyperplasia, in association with a genetically linked predisposal to structural cardiovascular adaptation, either 'inherent' in the effectors and/or caused by 'trophic' influences of a hormonal and/or transmitter nature."} {"id": "PMID:155502", "title": "[Mediastinoscopy in haematosarcomas (author's transl)].", "content": "Mediastinoscopy allows mediastinal examination through a cervical pathway. 17 mediastinoscopies were performed on 15 children with lymphomas (5 Hodgkin disease, 10 non Hodgkin malignant lymphomas). The diagnosis was assessed by mediastinoscopy on 10 patients which had only an abnormal mediastinal opacity and were free from extrathoracic localisation. This endoscopy was done on 5 children associated with a staging laparotomy to establish a prognosis and to investigate the spread of the disease before or during treatment. Diagnosis was obtained in 14 of the 15 patients. No surgical complications was observed. However, emergency care was necessary after two anaesthesical accidents in 2 children with malignant lymphomas. Mediastinoscopy is unfrequently required in children. Although in non surgical disease such as lymphomas, it may avoid an unnecessary thoracotomy and be repeated without damage.", "contents": "[Mediastinoscopy in haematosarcomas (author's transl)]. Mediastinoscopy allows mediastinal examination through a cervical pathway. 17 mediastinoscopies were performed on 15 children with lymphomas (5 Hodgkin disease, 10 non Hodgkin malignant lymphomas). The diagnosis was assessed by mediastinoscopy on 10 patients which had only an abnormal mediastinal opacity and were free from extrathoracic localisation. This endoscopy was done on 5 children associated with a staging laparotomy to establish a prognosis and to investigate the spread of the disease before or during treatment. Diagnosis was obtained in 14 of the 15 patients. No surgical complications was observed. However, emergency care was necessary after two anaesthesical accidents in 2 children with malignant lymphomas. Mediastinoscopy is unfrequently required in children. Although in non surgical disease such as lymphomas, it may avoid an unnecessary thoracotomy and be repeated without damage."} {"id": "PMID:155504", "title": "Glycolysis measurements in red cells from drug-treated epileptic and anaemia patients.", "content": "Glycolytic activity was measured in red cells from epileptic patients treated with anticonvulsant drugs. These results are compared with measurements of red cell glycolytic activity from megaloblastic anaemia patients and normal controls. The differences obtained between epileptic patients and controls, as well as the differences between anaemia, epileptic patients and controls is discussed.", "contents": "Glycolysis measurements in red cells from drug-treated epileptic and anaemia patients. Glycolytic activity was measured in red cells from epileptic patients treated with anticonvulsant drugs. These results are compared with measurements of red cell glycolytic activity from megaloblastic anaemia patients and normal controls. The differences obtained between epileptic patients and controls, as well as the differences between anaemia, epileptic patients and controls is discussed."} {"id": "PMID:155507", "title": "Evaluation of a topical steroid antibiotic combination (halcinonide-neomycin-amphotericin) in the treatment of cutaneous candidiasis and inflammatory dermatoses.", "content": "Halcinonide-neomycin-amphotericin (HNA) cream was evaluated in the treatment of cutaneous candidiasis and inflammatory dermatoses. The anti-candidal properties of HNA were assessed in a parallel comparison with iodochlorhydroxyquin-hydrocortisone (I-HC) as the control drug. The overall therapeutic response with HNA was excellent in 38 (95%) of 40 patients as compared to 17 (43%) of 40 treated with I-HC. In 50 patients treated for psoriasis, eczematous dermatitis, or neurodermatitis, HNA was evaluated in a paired comparison with hydrocortisone (HC). The overall therapeutic response with HNA was excellent in 36 (72%) patients as compared to 18 (36%) with HC. There were no adverse reactions with HNA or the control drugs.", "contents": "Evaluation of a topical steroid antibiotic combination (halcinonide-neomycin-amphotericin) in the treatment of cutaneous candidiasis and inflammatory dermatoses. Halcinonide-neomycin-amphotericin (HNA) cream was evaluated in the treatment of cutaneous candidiasis and inflammatory dermatoses. The anti-candidal properties of HNA were assessed in a parallel comparison with iodochlorhydroxyquin-hydrocortisone (I-HC) as the control drug. The overall therapeutic response with HNA was excellent in 38 (95%) of 40 patients as compared to 17 (43%) of 40 treated with I-HC. In 50 patients treated for psoriasis, eczematous dermatitis, or neurodermatitis, HNA was evaluated in a paired comparison with hydrocortisone (HC). The overall therapeutic response with HNA was excellent in 36 (72%) patients as compared to 18 (36%) with HC. There were no adverse reactions with HNA or the control drugs."} {"id": "PMID:155513", "title": "Early identification of handicapped children: a time for social work involvement.", "content": "Early identification of handicapping conditions in children greatly enhances the possibility of treatment that may limit malfunctioning. Social work has responsibility and an opportunity to become more active in early identification.", "contents": "Early identification of handicapped children: a time for social work involvement. Early identification of handicapping conditions in children greatly enhances the possibility of treatment that may limit malfunctioning. Social work has responsibility and an opportunity to become more active in early identification."} {"id": "PMID:155516", "title": "Analysis and modelling of human motor control systems.", "content": "In this contribution the aims and possibilities of model studies and simulations are briefly discussed. Next, a simulation kit for the peripheral motor control system is presented in outline and, finally, some results which can be obtained with it are given.", "contents": "Analysis and modelling of human motor control systems. In this contribution the aims and possibilities of model studies and simulations are briefly discussed. Next, a simulation kit for the peripheral motor control system is presented in outline and, finally, some results which can be obtained with it are given."} {"id": "PMID:155518", "title": "A physiological approach to motor disorders.", "content": "Spasticity in man is presented as a disinhibition of spinal cord mechanisms, the responses to stretch depending on the interaction of the reflex effects of group Ia with those of group II afferent fibres. The reflex responses to muscle stretch and shortening in Parkinson's disease do not depend on an abnormality of spinal reflex mechanisms. The superimposition of physiological tremor or alternating tremor in rigidity produces the classical cog-wheel sensation. The phase lead of the action tonic stretch reflex was found to be reduced in patients with athetosis and cerebellar disease, thus diminishing damping of unwanted movements. The more complex transmission characteristics of the action tonic stretch reflex of normal man are absent in patients with spasticity and cerebellar lesions, presumably due to interference with long-loop pathways. In normal subjects gain of the reflex loop increases with voluntary contraction but in spasticity gain remains high irrespective of contraction level.", "contents": "A physiological approach to motor disorders. Spasticity in man is presented as a disinhibition of spinal cord mechanisms, the responses to stretch depending on the interaction of the reflex effects of group Ia with those of group II afferent fibres. The reflex responses to muscle stretch and shortening in Parkinson's disease do not depend on an abnormality of spinal reflex mechanisms. The superimposition of physiological tremor or alternating tremor in rigidity produces the classical cog-wheel sensation. The phase lead of the action tonic stretch reflex was found to be reduced in patients with athetosis and cerebellar disease, thus diminishing damping of unwanted movements. The more complex transmission characteristics of the action tonic stretch reflex of normal man are absent in patients with spasticity and cerebellar lesions, presumably due to interference with long-loop pathways. In normal subjects gain of the reflex loop increases with voluntary contraction but in spasticity gain remains high irrespective of contraction level."} {"id": "PMID:155520", "title": "Phosphofructokinase isozymes from human organs and blood cells.", "content": "Phosphofructokinase (PFK) isozymes of blood cells and some human tissues were studied by starch gel electrophoresis and immunoprecipitation by anti-muscle and anti-erythrocyte PFK sera. PFK from muscle, heart, brain and placenta were totally precipitated by both antisera. PFK from blood cells (erythrocytes, lymphocytes, granulocytes, platelets) were precipitated more strongly by anti-erythrocyte PFK serum than by anti-muscle PFK serum. Liver, kidney and monoblast PFK were slightly precipitated by both antisera. From the electrophoretic patterns and the immunoprecipitation curves we may conclude that muscle contains the homotetrameric M4 forms; platelet, liver and kidney the homotetrameric E4 form, and blood cells the M-E hybrids. Monoblasts probably contain a E4 type PFK precursor, and heart, placenta and brain, a modified M4 type PFK. Other isozymes, unrelated with muscle and erythrocyte, were revealed in liver and kidney.", "contents": "Phosphofructokinase isozymes from human organs and blood cells. Phosphofructokinase (PFK) isozymes of blood cells and some human tissues were studied by starch gel electrophoresis and immunoprecipitation by anti-muscle and anti-erythrocyte PFK sera. PFK from muscle, heart, brain and placenta were totally precipitated by both antisera. PFK from blood cells (erythrocytes, lymphocytes, granulocytes, platelets) were precipitated more strongly by anti-erythrocyte PFK serum than by anti-muscle PFK serum. Liver, kidney and monoblast PFK were slightly precipitated by both antisera. From the electrophoretic patterns and the immunoprecipitation curves we may conclude that muscle contains the homotetrameric M4 forms; platelet, liver and kidney the homotetrameric E4 form, and blood cells the M-E hybrids. Monoblasts probably contain a E4 type PFK precursor, and heart, placenta and brain, a modified M4 type PFK. Other isozymes, unrelated with muscle and erythrocyte, were revealed in liver and kidney."} {"id": "PMID:155523", "title": "ATP synthesis and hydrolysis in chloroplast membranes. Differential inhibition by antibodies to chloroplast coupling factor 1.", "content": "1. Divalent antibodies against chloroplast coupling factor 1 inhibited the factor ATPase, ATP synthesis, hydrolysis and Pi-ATP exchange in chloroplasts. These antibodies also inhibited coupled electron flow rates but not the basal or uncoupled rates. 2. Several types of non-precipitating, modified antibodies prepared from the original antibody preparation strongly inhibited the ATPase and Pi-ATP exchange reaction but had little effect on ATP formation. 3. It is suggested that the inhibition of ATP synthesis by the divalent antibodies is probably due to an indirect blocking of the active site, while the inhibition of ATP-utilizing reactions by the modified antibodies is related to their effect on the transfer of ATP from a non-catalytic to a catalytic site on coupling factor 1, via an energy-dependent conformational change.", "contents": "ATP synthesis and hydrolysis in chloroplast membranes. Differential inhibition by antibodies to chloroplast coupling factor 1. 1. Divalent antibodies against chloroplast coupling factor 1 inhibited the factor ATPase, ATP synthesis, hydrolysis and Pi-ATP exchange in chloroplasts. These antibodies also inhibited coupled electron flow rates but not the basal or uncoupled rates. 2. Several types of non-precipitating, modified antibodies prepared from the original antibody preparation strongly inhibited the ATPase and Pi-ATP exchange reaction but had little effect on ATP formation. 3. It is suggested that the inhibition of ATP synthesis by the divalent antibodies is probably due to an indirect blocking of the active site, while the inhibition of ATP-utilizing reactions by the modified antibodies is related to their effect on the transfer of ATP from a non-catalytic to a catalytic site on coupling factor 1, via an energy-dependent conformational change."} {"id": "PMID:155528", "title": "Cooperation between subclass of T lymphocytes in the in vitro generation of cytotoxicity against a mutant H-2K difference. An analysis with anti-Lyt antisera.", "content": "The cellular requirements for the generation of cytotoxicity in mixed lymphocyte reaction (MLR) across an H-2K mutant difference were analyzed. Treatment of C57BL/6 lymphocytes with either anti-Lyt-1 or anti-Lyt-2 serum and complement strongly reduced their capacity to mount a cytotoxic response against the B6.C-H-2ba mutant. Almost complete reconstitution of the cytotoxic response occurred when a mixture of anti-Lyt-1 and anti-Lyt-2-treated cells was allowed to respond. Once cytotoxicity was generated, only anti-Lyt-2 serum affected it. It is concluded that in the cytotoxic response to the ba mutant, Lyt-1 helper cells collaborate with Lyt-2,3 killer cell precursors in the generation of Lyt-2,3 killer cells. Lyt-1,2,3 cells play, if any, a minor role in the generation of cytotoxicity. By comparison, the capacity to generate killer cells in MLR against an H-2K + IA difference was only affected by anti-Lyt-2 and not by anti-Lyt-1 serum, indicating that this response is relatively independent of help by Lyt-1 cells under the conditions tested.", "contents": "Cooperation between subclass of T lymphocytes in the in vitro generation of cytotoxicity against a mutant H-2K difference. An analysis with anti-Lyt antisera. The cellular requirements for the generation of cytotoxicity in mixed lymphocyte reaction (MLR) across an H-2K mutant difference were analyzed. Treatment of C57BL/6 lymphocytes with either anti-Lyt-1 or anti-Lyt-2 serum and complement strongly reduced their capacity to mount a cytotoxic response against the B6.C-H-2ba mutant. Almost complete reconstitution of the cytotoxic response occurred when a mixture of anti-Lyt-1 and anti-Lyt-2-treated cells was allowed to respond. Once cytotoxicity was generated, only anti-Lyt-2 serum affected it. It is concluded that in the cytotoxic response to the ba mutant, Lyt-1 helper cells collaborate with Lyt-2,3 killer cell precursors in the generation of Lyt-2,3 killer cells. Lyt-1,2,3 cells play, if any, a minor role in the generation of cytotoxicity. By comparison, the capacity to generate killer cells in MLR against an H-2K + IA difference was only affected by anti-Lyt-2 and not by anti-Lyt-1 serum, indicating that this response is relatively independent of help by Lyt-1 cells under the conditions tested."} {"id": "PMID:155529", "title": "Interferon production in the murine mixed lymphocyte culture. I. Interferon production caused by differences in the H-2 K and H-2 D region but not by differences in the I region or the M locus.", "content": "Little has been made previously of the observation that interferon is generated in the murine mixed lymphocyte reaction (MLR). We have found high levels of interferon in the supernatants of MLR between spleen cells of mice of different H-2 type after one to two days of culture. Interferon production was also seen in strain combinations that differed only in the K or D region of the H-2 complex. There was no production of interferon in strain combinations differing in the M locus or in the I region of the H-2 complex. The latter combinations are known not to induce cytotoxic effector cells. Thus, there seems to be a dichotomy in allogeneic determinants between those of the I region and of the M locus inducing primarily lymphoproliferation, and those of H-2K and H-2D inducing cytotoxic activity and interferon production.", "contents": "Interferon production in the murine mixed lymphocyte culture. I. Interferon production caused by differences in the H-2 K and H-2 D region but not by differences in the I region or the M locus. Little has been made previously of the observation that interferon is generated in the murine mixed lymphocyte reaction (MLR). We have found high levels of interferon in the supernatants of MLR between spleen cells of mice of different H-2 type after one to two days of culture. Interferon production was also seen in strain combinations that differed only in the K or D region of the H-2 complex. There was no production of interferon in strain combinations differing in the M locus or in the I region of the H-2 complex. The latter combinations are known not to induce cytotoxic effector cells. Thus, there seems to be a dichotomy in allogeneic determinants between those of the I region and of the M locus inducing primarily lymphoproliferation, and those of H-2K and H-2D inducing cytotoxic activity and interferon production."} {"id": "PMID:155530", "title": "MLR blast cells generated in mutant-standard strain combinations bind H-2K and H-2D antigens.", "content": "Strains CBA (M523) (= M523) and CBA differ by a mutation which has been mapped genetically into the K region of the H-2 complex. Similarly, strains B 10.D2 (M504 (= M504) and b 10.D2 differ in a mutation which occurred in the D region. The data presented in this study show that mixed lymphocyte culture in M523 anti-CBA and M504 anti-B 10.D2 strain combinations leads to the release of membrane fragments from the stimulating cells and binding of these fragments by blast cells. The fragments always carry H-2K (in the M523 anti-CBA combination) or H-2D (in the M504 anti-B 10.D2 combination) antigens present in the stimulating and absent in the responding cells (antigens H-2.60 and H-2.40, respectively). Although Ia antigens may occasionally be present on the CBA membrane fragments, these antigens do not participate in the M523 anti-CBA MLR stimulation. The data thus demonstrate that serologically detectable H-2K and H-2D antigens can induce a MLR and that a mutation can change properties of H-2K or H-2D molecules so that the alteration is detectable by both serological means and lymphocyte activation assays.", "contents": "MLR blast cells generated in mutant-standard strain combinations bind H-2K and H-2D antigens. Strains CBA (M523) (= M523) and CBA differ by a mutation which has been mapped genetically into the K region of the H-2 complex. Similarly, strains B 10.D2 (M504 (= M504) and b 10.D2 differ in a mutation which occurred in the D region. The data presented in this study show that mixed lymphocyte culture in M523 anti-CBA and M504 anti-B 10.D2 strain combinations leads to the release of membrane fragments from the stimulating cells and binding of these fragments by blast cells. The fragments always carry H-2K (in the M523 anti-CBA combination) or H-2D (in the M504 anti-B 10.D2 combination) antigens present in the stimulating and absent in the responding cells (antigens H-2.60 and H-2.40, respectively). Although Ia antigens may occasionally be present on the CBA membrane fragments, these antigens do not participate in the M523 anti-CBA MLR stimulation. The data thus demonstrate that serologically detectable H-2K and H-2D antigens can induce a MLR and that a mutation can change properties of H-2K or H-2D molecules so that the alteration is detectable by both serological means and lymphocyte activation assays."} {"id": "PMID:155534", "title": "Genetic and evolutionary aspects of aging.", "content": "Four questions of fundamental importance to gerontology are considered. 1) The number of genes involved in aging--in the case of man, an analysis of the phenotypes of relevant spontaneous mutants indicates that aging is highly polygenic. 2) General categories of genes--regulator genes may be more relevant than structural genes: a) three aneuploid disorders, Down's, Turner's and Klinefelter's syndromes, ranked among the top 10 candidates as \"segmental progeroid syndromes\" when compared with 162 single gene disorders of relevance to the pathobiology of aging; b) the rates at which maximum life spans have been increasing, especially among hominids, have probably been too rapid to be accounted for by changes in the amino acid sequences of proteins; c) a preliminary analysis of the variance of maximum life spans among a few orders of mammals is suggestive of a linear correlation with the indexes of rates of chromosomal evolution, as estimated by Bush et al. (Proc. Natl. Acad. Sci. USA 74: 3942-3946, 1977). 3) Nature of gene action--although there are reasons for invoking genes that modulate the rates of accumulation of somatic mutations, differential regulation of development is likely to be a major setting for gene action. 4) New approaches to formal genetic analysis of aging--advances in experimental embryology and somatic cell genetics offer such opportunities.", "contents": "Genetic and evolutionary aspects of aging. Four questions of fundamental importance to gerontology are considered. 1) The number of genes involved in aging--in the case of man, an analysis of the phenotypes of relevant spontaneous mutants indicates that aging is highly polygenic. 2) General categories of genes--regulator genes may be more relevant than structural genes: a) three aneuploid disorders, Down's, Turner's and Klinefelter's syndromes, ranked among the top 10 candidates as \"segmental progeroid syndromes\" when compared with 162 single gene disorders of relevance to the pathobiology of aging; b) the rates at which maximum life spans have been increasing, especially among hominids, have probably been too rapid to be accounted for by changes in the amino acid sequences of proteins; c) a preliminary analysis of the variance of maximum life spans among a few orders of mammals is suggestive of a linear correlation with the indexes of rates of chromosomal evolution, as estimated by Bush et al. (Proc. Natl. Acad. Sci. USA 74: 3942-3946, 1977). 3) Nature of gene action--although there are reasons for invoking genes that modulate the rates of accumulation of somatic mutations, differential regulation of development is likely to be a major setting for gene action. 4) New approaches to formal genetic analysis of aging--advances in experimental embryology and somatic cell genetics offer such opportunities."} {"id": "PMID:155540", "title": "[Angiolymphoid hyperplasia with follicular mucinosis].", "content": "Association of angiolymphoid hyperplasia (pseudopyogenic granuloma type) and follicular mucinosis in the same lesion on the scalp of a 30-year-old woman. A similar case has been reported recently.", "contents": "[Angiolymphoid hyperplasia with follicular mucinosis]. Association of angiolymphoid hyperplasia (pseudopyogenic granuloma type) and follicular mucinosis in the same lesion on the scalp of a 30-year-old woman. A similar case has been reported recently."} {"id": "PMID:155546", "title": "Determinants of the rate of intestinal absorption of oral cholecystographic contrast agents in the dog jejunum.", "content": "Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present.", "contents": "Determinants of the rate of intestinal absorption of oral cholecystographic contrast agents in the dog jejunum. Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present."} {"id": "PMID:155547", "title": "Evidence against the presence of circulating immune complexes in chronic inflammatory bowel disease.", "content": "Several investigators have reported the presence of circulating immune complexes in serum from patients with Crohn's disease and chronic ulcerative colitis. Because previous assays employed conditions which might have caused immunoglobulin aggregates to form in vitro, thus falsely suggesting the presence of immune complexes in vivo, we tested inflammatory bowel disease sera for immune complexes using four assays designed to minimize in vitro immunoglobulin aggregation. In three assays immune complexes were not detectable, while in a fourth, the Clq precipitin test, positive reactions occurred. These precipitin reactions did not have characteristics of immune complexes. Our data suggest that circulating immune complexes are either not present in patients with inflammatory bowel disease or that they occur infrequently or in low concentration.", "contents": "Evidence against the presence of circulating immune complexes in chronic inflammatory bowel disease. Several investigators have reported the presence of circulating immune complexes in serum from patients with Crohn's disease and chronic ulcerative colitis. Because previous assays employed conditions which might have caused immunoglobulin aggregates to form in vitro, thus falsely suggesting the presence of immune complexes in vivo, we tested inflammatory bowel disease sera for immune complexes using four assays designed to minimize in vitro immunoglobulin aggregation. In three assays immune complexes were not detectable, while in a fourth, the Clq precipitin test, positive reactions occurred. These precipitin reactions did not have characteristics of immune complexes. Our data suggest that circulating immune complexes are either not present in patients with inflammatory bowel disease or that they occur infrequently or in low concentration."} {"id": "PMID:155548", "title": "[Secondary extra-uterine pregnancy (author's transl)].", "content": "The article reports on a patient with secondary extra-uterine pregnancy during the 20th pregnancy week. The highly multifaceted symptoms and the diagnostic possibilities are discussed on the basis of this case. Laparoscopy is rated decisively important.", "contents": "[Secondary extra-uterine pregnancy (author's transl)]. The article reports on a patient with secondary extra-uterine pregnancy during the 20th pregnancy week. The highly multifaceted symptoms and the diagnostic possibilities are discussed on the basis of this case. Laparoscopy is rated decisively important."} {"id": "PMID:155549", "title": "[\"Second-look laparoscopy\" (author's transl)].", "content": "The authors present a report on their experience with the so-called \"second-look laparoscopy\" which they have been performing systematically since 1974. 44 (12%) second-look laparoscopies were done among a total of 383 laparoscopies during 1974--1977. Second-look laparoscopy was performed on routine basis in women treated by radiology and/or pharmacotherapy for advanced carcinoma of the genitals, especially in the case of ovarian carcinoma. The diagnostic measure represents an important contribution to establishing whether chemotherapy has been successfull, especially in ovarian cancer.", "contents": "[\"Second-look laparoscopy\" (author's transl)]. The authors present a report on their experience with the so-called \"second-look laparoscopy\" which they have been performing systematically since 1974. 44 (12%) second-look laparoscopies were done among a total of 383 laparoscopies during 1974--1977. Second-look laparoscopy was performed on routine basis in women treated by radiology and/or pharmacotherapy for advanced carcinoma of the genitals, especially in the case of ovarian carcinoma. The diagnostic measure represents an important contribution to establishing whether chemotherapy has been successfull, especially in ovarian cancer."} {"id": "PMID:155550", "title": "Treatment of Paget's disease of bone.", "content": "A brief review is given of the use of fluoride, mithramycin, glucagon, actinomycin D, calcitonins and diphosphonates for treatment of Paget's disease of bone. The decision regarding treatment, effectiveness of the drugs, the incidence of side effects and assessment of clinical, biochemical, histological, radiological and thermographic responses are discussed.", "contents": "Treatment of Paget's disease of bone. A brief review is given of the use of fluoride, mithramycin, glucagon, actinomycin D, calcitonins and diphosphonates for treatment of Paget's disease of bone. The decision regarding treatment, effectiveness of the drugs, the incidence of side effects and assessment of clinical, biochemical, histological, radiological and thermographic responses are discussed."} {"id": "PMID:155562", "title": "Enzyme histochemical alterations in human skeletal muscles after tenotomy and after spontaneous rupture of the tendon.", "content": "The authors studied the histochemical alterations of human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type I fibers), and myofibrillar ATP-ase (in type 2 fibers) activity was decreased in all injured muscles. In the intact antagonists and contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected muscles. Two weeks or more after the injury of the tendon in injured muscles the number of type 1 fibers were decreased and therefore a mathematically significant type 2 fibre predominance occurred. Atrophy involve both type 1 and type 2 fibers, but type 1 fibre atrophy was more pronunced as type 2 fibre atrophy.", "contents": "Enzyme histochemical alterations in human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. The authors studied the histochemical alterations of human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type I fibers), and myofibrillar ATP-ase (in type 2 fibers) activity was decreased in all injured muscles. In the intact antagonists and contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected muscles. Two weeks or more after the injury of the tendon in injured muscles the number of type 1 fibers were decreased and therefore a mathematically significant type 2 fibre predominance occurred. Atrophy involve both type 1 and type 2 fibers, but type 1 fibre atrophy was more pronunced as type 2 fibre atrophy."} {"id": "PMID:155563", "title": "[Effect of 1 alpha-hydroxycholecalciferol on cellular calcium metabolism of kidney cortex (author's transl)].", "content": "Rats were provided a normal laboratory diet or a low Ca.vitamin D-deficient diet. After the administration of 1 alpha-hydroxycholecalciferol, mitochondria, microsomes and slices were prepared from kidney cortex of both control and treated rats. When 1 alpha-hydroxycholecalciferol was given to normal and low Ca.vitamin D-deficient rats, Ca accumulation in mitochondria was stimulated during 30 minutes and the high calcium content was maintained at the subsequent incubation. There was a significant decrease of mitochondrial Ca2+-ATPase and Mg2+-ATPase activities with low Ca.vitamin D depletion, but both enzyme activities were restored by 1 alpha-hydroxycholecalciferol treatment of the depleted rats. Ca2+-ATPase and Mg2+-ATPase activities of microsomes were not altered with the administration of 1 alha-hydroxycholecalciferol. In contrast to results of mitochondrial Ca transport, changes in Ca influx and efflux of slices were not significant in response to the treatment of low Ca.vitamin D-deficient rats with 1 alpha-hydroxycholecalciferol. The results of the present study suggest that 1 alpha-hydroxycholecalciferol plays a role in the process of Ca accumulation and ATP hydrolysis of mitochondria in kidney cortex.", "contents": "[Effect of 1 alpha-hydroxycholecalciferol on cellular calcium metabolism of kidney cortex (author's transl)]. Rats were provided a normal laboratory diet or a low Ca.vitamin D-deficient diet. After the administration of 1 alpha-hydroxycholecalciferol, mitochondria, microsomes and slices were prepared from kidney cortex of both control and treated rats. When 1 alpha-hydroxycholecalciferol was given to normal and low Ca.vitamin D-deficient rats, Ca accumulation in mitochondria was stimulated during 30 minutes and the high calcium content was maintained at the subsequent incubation. There was a significant decrease of mitochondrial Ca2+-ATPase and Mg2+-ATPase activities with low Ca.vitamin D depletion, but both enzyme activities were restored by 1 alpha-hydroxycholecalciferol treatment of the depleted rats. Ca2+-ATPase and Mg2+-ATPase activities of microsomes were not altered with the administration of 1 alha-hydroxycholecalciferol. In contrast to results of mitochondrial Ca transport, changes in Ca influx and efflux of slices were not significant in response to the treatment of low Ca.vitamin D-deficient rats with 1 alpha-hydroxycholecalciferol. The results of the present study suggest that 1 alpha-hydroxycholecalciferol plays a role in the process of Ca accumulation and ATP hydrolysis of mitochondria in kidney cortex."} {"id": "PMID:155564", "title": "[Computer tomography of the cervical spinal canal following intrathecal enhancement: cervical CT myelography. Studies on technic and the initial results (author' transl)].", "content": "Computer tomography of the cervical spinal canal was carried out in 54 patients after the intrathecal injection of metrizamide (CT myelography). In 43 patients this was done after conventional myelography, in eleven it was the primary examination. In 32 patients the examination proved normal and in 22 abnormal. Correlation between the CT findings and conventional myelography was excellent. Quite small intraspinal structures both normal and abnormal, could be demonstrated. CT myelography is particularly valuable for determining the special relationships within the vertebral canal. The procedure can supplement and confirm conventional myelography, for instance round the foramen magnum. Under certain circumstances it may be regarded as the method of choice, since it is simpler for the patient and less likely to produce complications due to the contrast medium.", "contents": "[Computer tomography of the cervical spinal canal following intrathecal enhancement: cervical CT myelography. Studies on technic and the initial results (author' transl)]. Computer tomography of the cervical spinal canal was carried out in 54 patients after the intrathecal injection of metrizamide (CT myelography). In 43 patients this was done after conventional myelography, in eleven it was the primary examination. In 32 patients the examination proved normal and in 22 abnormal. Correlation between the CT findings and conventional myelography was excellent. Quite small intraspinal structures both normal and abnormal, could be demonstrated. CT myelography is particularly valuable for determining the special relationships within the vertebral canal. The procedure can supplement and confirm conventional myelography, for instance round the foramen magnum. Under certain circumstances it may be regarded as the method of choice, since it is simpler for the patient and less likely to produce complications due to the contrast medium."} {"id": "PMID:155565", "title": "[The collateral circulation due to cerebral arterio-venous malformation and occlusions of major cranial vessels (author's transl)].", "content": "Arteriovenous malformations (AVM) of the brain are diagnosed mostly in the early adult life. With the come up of Computerized Tomography (CT) which often is done without the strong indications as postulated for the conventional neuroradiologic examinations, asymptomatic AVM in the elderly population may be found. Since May 1977 4 asymptomatic arteriovenous malformations were diagnosed in our institution using CT. 2 of these patients had severe degenerative changes of the great cerebral vessels and an unusual collateral circulation developed probably because of the steal-phenomenon in the vascular malformation. These 2 cases allow to study all possibilities of cerebral collateral circulation. Uncommon in one of the cases was a capillary anastomotic network through the thalami, in the other case an extensive dural rete mirabile developed. The problems of collateral circulation are discussed.", "contents": "[The collateral circulation due to cerebral arterio-venous malformation and occlusions of major cranial vessels (author's transl)]. Arteriovenous malformations (AVM) of the brain are diagnosed mostly in the early adult life. With the come up of Computerized Tomography (CT) which often is done without the strong indications as postulated for the conventional neuroradiologic examinations, asymptomatic AVM in the elderly population may be found. Since May 1977 4 asymptomatic arteriovenous malformations were diagnosed in our institution using CT. 2 of these patients had severe degenerative changes of the great cerebral vessels and an unusual collateral circulation developed probably because of the steal-phenomenon in the vascular malformation. These 2 cases allow to study all possibilities of cerebral collateral circulation. Uncommon in one of the cases was a capillary anastomotic network through the thalami, in the other case an extensive dural rete mirabile developed. The problems of collateral circulation are discussed."} {"id": "PMID:155566", "title": "[High contrast doses for peripheral and cerebral angiography (author's transl)].", "content": "Angiography, using a standard method, was carried out on 100 patients with arterial occlusive disease involving the cerebral and/or peripheral vessels. It was shown that contrast medium with a high iodine content could be used in the relatively high dose of 80 ml. with an injection rate of 30 ml/sec. in the cerebral circulation without producing any complications. For pelvic and lower limb arteriography, 80 ml. contrast was injected at a rate of 12 to 18 ml/sec. This was well tolerated, but produced \"vascular pain\" like all commercially available contrast media. Total contrast amounts reached 300 ml. and 4.8 ml/kg. body weight and were tolerated without any clinical evidence of toxicity. Mild side effects were observed in seven patients, unrelated to the amount of contrast or the type of contrast or the region investigated. These changes resolved rapidly without treatment. As a rule the vessels demonstrated angiographically showed good contrast and were easily seen.", "contents": "[High contrast doses for peripheral and cerebral angiography (author's transl)]. Angiography, using a standard method, was carried out on 100 patients with arterial occlusive disease involving the cerebral and/or peripheral vessels. It was shown that contrast medium with a high iodine content could be used in the relatively high dose of 80 ml. with an injection rate of 30 ml/sec. in the cerebral circulation without producing any complications. For pelvic and lower limb arteriography, 80 ml. contrast was injected at a rate of 12 to 18 ml/sec. This was well tolerated, but produced \"vascular pain\" like all commercially available contrast media. Total contrast amounts reached 300 ml. and 4.8 ml/kg. body weight and were tolerated without any clinical evidence of toxicity. Mild side effects were observed in seven patients, unrelated to the amount of contrast or the type of contrast or the region investigated. These changes resolved rapidly without treatment. As a rule the vessels demonstrated angiographically showed good contrast and were easily seen."} {"id": "PMID:155567", "title": "[Bilateral selective renal angiography--a procedure worth while? Report of the incidence of bilateral space-occupying lesions of the kidney in 2721 selective renal angiographies (author's transl)].", "content": "Since surgeons can save part of one kidney either by partial resection or reimplantation following \"workbench\" surgery, it has become increasingly important for the radiologist to demonstrate bilateral space-occupying lesions of the kidneys by bilateral selective angiography, magnification technique and computerized tomography of the kidneys. Fine-needle puncture of the kidney is an important additive technique to solve differential diagnostic problems of avascular, space-occupying renal lesions. Moreover it is a great comfort to the surgeon to know the appearance of both kidneys and may also modify the planned surgical procedure considerably. The incidence of 93 cases of bilateral space occupying lesions of the kidneys, diagnosed in 2721 selective renal angiographies over a period of 13 years, suggests that these entities are more frequent than previously thought.", "contents": "[Bilateral selective renal angiography--a procedure worth while? Report of the incidence of bilateral space-occupying lesions of the kidney in 2721 selective renal angiographies (author's transl)]. Since surgeons can save part of one kidney either by partial resection or reimplantation following \"workbench\" surgery, it has become increasingly important for the radiologist to demonstrate bilateral space-occupying lesions of the kidneys by bilateral selective angiography, magnification technique and computerized tomography of the kidneys. Fine-needle puncture of the kidney is an important additive technique to solve differential diagnostic problems of avascular, space-occupying renal lesions. Moreover it is a great comfort to the surgeon to know the appearance of both kidneys and may also modify the planned surgical procedure considerably. The incidence of 93 cases of bilateral space occupying lesions of the kidneys, diagnosed in 2721 selective renal angiographies over a period of 13 years, suggests that these entities are more frequent than previously thought."} {"id": "PMID:155568", "title": "[Malignant tumours in horseshoe kidneys (author's transl)].", "content": "Hypernephromas were found in horseshoe kidneys in two patients; the diagnostic problems arising from this combination are discussed. Detailed demonstration of horseshoe kidneys by excretion urograms may be poor and tumours may therefore be overlooked and, on palpation, an abnormality within the gastrointestinal tract may be simulated. Angiography usually indicates the diagnosis and helps in planning surgery. Although there is no increase in the incidence of adeno-carcinomas in horseshoe kidneys, there is a significant increase in the incidence of Wilm's tumours and of carcinomas of the renal pelvis. Treatment consists of heminephrectomy or resection of the tumour; complications are relatively common.", "contents": "[Malignant tumours in horseshoe kidneys (author's transl)]. Hypernephromas were found in horseshoe kidneys in two patients; the diagnostic problems arising from this combination are discussed. Detailed demonstration of horseshoe kidneys by excretion urograms may be poor and tumours may therefore be overlooked and, on palpation, an abnormality within the gastrointestinal tract may be simulated. Angiography usually indicates the diagnosis and helps in planning surgery. Although there is no increase in the incidence of adeno-carcinomas in horseshoe kidneys, there is a significant increase in the incidence of Wilm's tumours and of carcinomas of the renal pelvis. Treatment consists of heminephrectomy or resection of the tumour; complications are relatively common."} {"id": "PMID:155569", "title": "[The scope and value of translumbar puncture of the renal pelvis (author's transl)].", "content": "Percutaneous translumbar pyelography is indicated when excretory urography has failed to demonstrate the cause or site of obstructive uropathy and retrograde pyelography is impossible, undesirable or contraindicated. Under prophylactic treatment with antibiotics translumbar antegrade pyelography is safe, simple and accurate and in selected cases the only diagnostic method to establish exact diagnosis without which appropriate therapy cannot be planned. The method is described and the results of 30 percutaneous translumbar pyelographies obtained from 2680 renal angiographies and 230 punctures of space-occupying lesions over 13 years are reported.", "contents": "[The scope and value of translumbar puncture of the renal pelvis (author's transl)]. Percutaneous translumbar pyelography is indicated when excretory urography has failed to demonstrate the cause or site of obstructive uropathy and retrograde pyelography is impossible, undesirable or contraindicated. Under prophylactic treatment with antibiotics translumbar antegrade pyelography is safe, simple and accurate and in selected cases the only diagnostic method to establish exact diagnosis without which appropriate therapy cannot be planned. The method is described and the results of 30 percutaneous translumbar pyelographies obtained from 2680 renal angiographies and 230 punctures of space-occupying lesions over 13 years are reported."} {"id": "PMID:155570", "title": "Fibrolipomatosis of the transplanted kidney.", "content": "Fibrolipomatosis of varying degree was observed in 24 transplanted kidneys. In 8 patients there was no history of urinary tract obstruction or multiple infections, leaving earlier rejection periods as the probable factor responsible for development of fibrolipomatosis after transplantation.", "contents": "Fibrolipomatosis of the transplanted kidney. Fibrolipomatosis of varying degree was observed in 24 transplanted kidneys. In 8 patients there was no history of urinary tract obstruction or multiple infections, leaving earlier rejection periods as the probable factor responsible for development of fibrolipomatosis after transplantation."} {"id": "PMID:155571", "title": "[Oro-pharyngeal oesophagus papillomatosis. Description of one case (author's transl)].", "content": "A case of oro-pharyngeal oesophagus papillomatosis is described. It was associated with an adeno-carcinoma of the stomach. A brief, critical review of the literature with consideration of the aetiology and pathology is given.", "contents": "[Oro-pharyngeal oesophagus papillomatosis. Description of one case (author's transl)]. A case of oro-pharyngeal oesophagus papillomatosis is described. It was associated with an adeno-carcinoma of the stomach. A brief, critical review of the literature with consideration of the aetiology and pathology is given."} {"id": "PMID:155572", "title": "[Evaluation of liver haemodynamics by spleno-portography in portal hypertension (author's transl)].", "content": "In 68 patients arterial and portal blood flow were measured by angiodensitometry in the course of routine, indirect splenoportography. Results were compared with those already published, with investigations of a model and with animal experiments. It was shown that, given certain underlying conditions, reliable results can be obtained even in the presence of a pulsatile flow and incomplete contrast mixing. Compared with other procedures, the method has the advantage of providing a complete picture of liver haemodynamics in the course of routine splenoportography in a simple way and without affecting the patient further. As a result the indications for performing a shunt and the choice of the shunt technique can be more accurately determined.", "contents": "[Evaluation of liver haemodynamics by spleno-portography in portal hypertension (author's transl)]. In 68 patients arterial and portal blood flow were measured by angiodensitometry in the course of routine, indirect splenoportography. Results were compared with those already published, with investigations of a model and with animal experiments. It was shown that, given certain underlying conditions, reliable results can be obtained even in the presence of a pulsatile flow and incomplete contrast mixing. Compared with other procedures, the method has the advantage of providing a complete picture of liver haemodynamics in the course of routine splenoportography in a simple way and without affecting the patient further. As a result the indications for performing a shunt and the choice of the shunt technique can be more accurately determined."} {"id": "PMID:155573", "title": "[Diagnostic criteria for pancreatic sonography during the course of uncomplicated acute pancreatitis (author's transl)].", "content": "The course of uncomplicated pancreatitis was followed by sonography in 45 patients. The changes during the disease and their temporal relationship to the clinical stage are illustrated by an example. During the initial phase of the disease the sonographic findings may be so slight that they are easily missed, although clinical symptoms are present. It is only during the main phase of the disease that the typical sonographic findings of acute pancreatitis develop. At this time, maximal increase in amylase activity has usually passed. During recovery, with uninterrupted clinical and biochemical improvement, changes in the sonogram can still be seen for between three weeks and four months.", "contents": "[Diagnostic criteria for pancreatic sonography during the course of uncomplicated acute pancreatitis (author's transl)]. The course of uncomplicated pancreatitis was followed by sonography in 45 patients. The changes during the disease and their temporal relationship to the clinical stage are illustrated by an example. During the initial phase of the disease the sonographic findings may be so slight that they are easily missed, although clinical symptoms are present. It is only during the main phase of the disease that the typical sonographic findings of acute pancreatitis develop. At this time, maximal increase in amylase activity has usually passed. During recovery, with uninterrupted clinical and biochemical improvement, changes in the sonogram can still be seen for between three weeks and four months."} {"id": "PMID:155574", "title": "[The sonographic differential diagnosis of supra and infra diaphragmatic processes (author's transl)].", "content": "The sonographic features and differential diagnosis of 95 supra and infra diaphragmatic processes are described. Sonographic demonstration of the diaphragm permits definite differentiation between simple and loculated pleural effusions from periparenchymatous fluid collections in the abdomen.", "contents": "[The sonographic differential diagnosis of supra and infra diaphragmatic processes (author's transl)]. The sonographic features and differential diagnosis of 95 supra and infra diaphragmatic processes are described. Sonographic demonstration of the diaphragm permits definite differentiation between simple and loculated pleural effusions from periparenchymatous fluid collections in the abdomen."} {"id": "PMID:155575", "title": "[Lymph node metastases--diagnosis by lymphography and CT (author's transl)].", "content": "The value of lymphography and CT in the diagnosis of abdominal lymph node metastases was compared in 82 patients with various types of malignant disease. In the presence of systemic disease or testicular tumours, CT increased the recognition of lymph node metastases and their extent, particularly of high para-aortic deposits which were frequently underestimated by lymphography. Lymph nodes in the pelvis are more easily identified. CT is the first choice for the investigation of systemic disease and testicular tumours. This will, in addition, also demonstrate abnormalities of the organs and assist in radiation planning. CT is a simple procedure which is also very valuable in following the effect of treatment. For metastases from other origins, lymphography is often more valuable since CT is unable to identify metastases in lymph nodes if these are not enlarged. The two methods complement each other and their combination provides improved diagnostic information.", "contents": "[Lymph node metastases--diagnosis by lymphography and CT (author's transl)]. The value of lymphography and CT in the diagnosis of abdominal lymph node metastases was compared in 82 patients with various types of malignant disease. In the presence of systemic disease or testicular tumours, CT increased the recognition of lymph node metastases and their extent, particularly of high para-aortic deposits which were frequently underestimated by lymphography. Lymph nodes in the pelvis are more easily identified. CT is the first choice for the investigation of systemic disease and testicular tumours. This will, in addition, also demonstrate abnormalities of the organs and assist in radiation planning. CT is a simple procedure which is also very valuable in following the effect of treatment. For metastases from other origins, lymphography is often more valuable since CT is unable to identify metastases in lymph nodes if these are not enlarged. The two methods complement each other and their combination provides improved diagnostic information."} {"id": "PMID:155576", "title": "[Percutaneous fine needle biopsy of lymph nodes (author's transl)].", "content": "Following lymphography, 76 lymph nodes were punctured percutaneously using a fine needle in 23 patients and an aspiration biopsy was performed. This simple procedure provided cytological comfirmation in cases of doubtful lymphograms. Systematic puncture of representative lymph nodes in the area of metastatic spread may at times be able to replace a staging operation.", "contents": "[Percutaneous fine needle biopsy of lymph nodes (author's transl)]. Following lymphography, 76 lymph nodes were punctured percutaneously using a fine needle in 23 patients and an aspiration biopsy was performed. This simple procedure provided cytological comfirmation in cases of doubtful lymphograms. Systematic puncture of representative lymph nodes in the area of metastatic spread may at times be able to replace a staging operation."} {"id": "PMID:155577", "title": "Angiography in synovitis of the knee.", "content": "In inappropriately treated synovitides of the knee joint with shift towards a villonodular inversion, an inflammatory angiographic symptomatology may be expected which is different according to the seriousness of the illness including (1) local hyperaemia, (2) deviation of arteries, (3) morphologic and formative vascular inversions and (4) diffusion of the contrast material into synovitic conglomerates and (5) shunts. From these findings the stadia of synovitis may be evaluated, including the extent and place of the villonodular inversion in the clinically or arthrographically inaccessible sites. Differential-diagnostic contributions to the origin of the synovitis cannot be expected from angiography and biochemical as well as bacteriological methods (cultivation) remain necessary. Despite this, angiography has its supplementary value in all cases where an analysis of synovitis is impossible by other means and also in all cases, where the extent of the synovitic changes must be evaluated for an operative treatment.", "contents": "Angiography in synovitis of the knee. In inappropriately treated synovitides of the knee joint with shift towards a villonodular inversion, an inflammatory angiographic symptomatology may be expected which is different according to the seriousness of the illness including (1) local hyperaemia, (2) deviation of arteries, (3) morphologic and formative vascular inversions and (4) diffusion of the contrast material into synovitic conglomerates and (5) shunts. From these findings the stadia of synovitis may be evaluated, including the extent and place of the villonodular inversion in the clinically or arthrographically inaccessible sites. Differential-diagnostic contributions to the origin of the synovitis cannot be expected from angiography and biochemical as well as bacteriological methods (cultivation) remain necessary. Despite this, angiography has its supplementary value in all cases where an analysis of synovitis is impossible by other means and also in all cases, where the extent of the synovitic changes must be evaluated for an operative treatment."} {"id": "PMID:155578", "title": "Roentgenmorphological muscle changes in anterior horn cell lesions.", "content": "The author examined muscles in the extremities of 42 poliomyelitis patients using a special roentgenological technique. This method made it possible to objectively determine the size of the muscles in the soft tissues of the extremities. The volume and distribution of the increased amounts of fatty tissue in the muscle and the volume of normal muscle tissue led to draw conclusions regarding the histological state of the muscle. Roentgenmorphological changes are closely linked to muscle dysfunction. Roentgenological examination of the soft tissue provides a useful supplement to a muscle biopsy and to electromyographic examinations and is of value for the rehabilitation of the patients.", "contents": "Roentgenmorphological muscle changes in anterior horn cell lesions. The author examined muscles in the extremities of 42 poliomyelitis patients using a special roentgenological technique. This method made it possible to objectively determine the size of the muscles in the soft tissues of the extremities. The volume and distribution of the increased amounts of fatty tissue in the muscle and the volume of normal muscle tissue led to draw conclusions regarding the histological state of the muscle. Roentgenmorphological changes are closely linked to muscle dysfunction. Roentgenological examination of the soft tissue provides a useful supplement to a muscle biopsy and to electromyographic examinations and is of value for the rehabilitation of the patients."} {"id": "PMID:155579", "title": "[Mammography in the diagnosis and treatment of non-puerperal mastitis (author's transl)].", "content": "Circumscribed or diffuse non-puerperal mastitis is usually associated with local signs of inflammation. In two-thirds of these cases it is possible to demonstrate the radiological features of mastitis. Mammography is an important diagnostic procedure in the demonstration of acute mastitis and its differentiation from an inflammatory carcinoma; it is also valuable in the control of treatment. The success of intensive antibiotic therapy with recovery of normal appearances in the chest can be observed objectively by mammography. In distinguishing mastitis from an inflammatory carcinoma, radiological evidence of regression under the influence of antibiotics is evidence in favour of mastitis.", "contents": "[Mammography in the diagnosis and treatment of non-puerperal mastitis (author's transl)]. Circumscribed or diffuse non-puerperal mastitis is usually associated with local signs of inflammation. In two-thirds of these cases it is possible to demonstrate the radiological features of mastitis. Mammography is an important diagnostic procedure in the demonstration of acute mastitis and its differentiation from an inflammatory carcinoma; it is also valuable in the control of treatment. The success of intensive antibiotic therapy with recovery of normal appearances in the chest can be observed objectively by mammography. In distinguishing mastitis from an inflammatory carcinoma, radiological evidence of regression under the influence of antibiotics is evidence in favour of mastitis."} {"id": "PMID:155580", "title": "[Experimental study on image quality when using screens in mammography (author's transl)].", "content": "1. Different type of screens and x-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2. Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1 : 10. 3. The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4. A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreases dosis.", "contents": "[Experimental study on image quality when using screens in mammography (author's transl)]. 1. Different type of screens and x-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2. Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1 : 10. 3. The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4. A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreases dosis."} {"id": "PMID:155581", "title": "[Dose measurements during mammography using a grid (author's transl)].", "content": "In order to increase film contrast, the Mammo Diagnost U (Philips) has been equipped with a newly developed grid. The apparatus was used with a film-screen combination in a clinical investigation (film: 3M type M, screen: Kodak Min R, cassette: Kodak Min R). The paper deals with dose measurements on patients and phantoms who had been x-rayed by the apparatus. Measurements were carried out with a low kv. chamber and a LiF dose meter which were calibrated for various kv. ranges. The tissue equivalent phantom was a modification of the phantom substance M3; this was preferred to the usual substances such as Plexiglass or Vestyron because of its more suitable physical properties. A breast compressed to 5 cm. irradiated with 35 kv. receives an entry dose of about 1.4mC/kg. (5.3 R) corresponding to a maximal surface dose of about 31 mGy (3.1 rd.). In order to determine radiation dose to patients, measurements were carried out on an Alderson phantom using four different techniques. Surface dose to the contralateral breast and the lens was about 1% and .1% of maximal surface dose of the irradiated breast. Gonadal dose was less than 0.4 muGy (40murd.) per exposure.", "contents": "[Dose measurements during mammography using a grid (author's transl)]. In order to increase film contrast, the Mammo Diagnost U (Philips) has been equipped with a newly developed grid. The apparatus was used with a film-screen combination in a clinical investigation (film: 3M type M, screen: Kodak Min R, cassette: Kodak Min R). The paper deals with dose measurements on patients and phantoms who had been x-rayed by the apparatus. Measurements were carried out with a low kv. chamber and a LiF dose meter which were calibrated for various kv. ranges. The tissue equivalent phantom was a modification of the phantom substance M3; this was preferred to the usual substances such as Plexiglass or Vestyron because of its more suitable physical properties. A breast compressed to 5 cm. irradiated with 35 kv. receives an entry dose of about 1.4mC/kg. (5.3 R) corresponding to a maximal surface dose of about 31 mGy (3.1 rd.). In order to determine radiation dose to patients, measurements were carried out on an Alderson phantom using four different techniques. Surface dose to the contralateral breast and the lens was about 1% and .1% of maximal surface dose of the irradiated breast. Gonadal dose was less than 0.4 muGy (40murd.) per exposure."} {"id": "PMID:155582", "title": "[Futher means for reducing radiation dose during exposure of the pelvis in infants (author's transl)].", "content": "A simple dose-saving procedure for the diagnosis of congenital hip dysplasia employing a diaphragm in nearfocus position is presented. Doses to the skin and the gonads were measured with a phantom for the new and other techniques. With optimal techniques the skin dose is smaller than 2 mR and the gonadal doses lie around 0.1 mR for both male and female patients. An estimate of the dose burden from undesired radiation is appended.", "contents": "[Futher means for reducing radiation dose during exposure of the pelvis in infants (author's transl)]. A simple dose-saving procedure for the diagnosis of congenital hip dysplasia employing a diaphragm in nearfocus position is presented. Doses to the skin and the gonads were measured with a phantom for the new and other techniques. With optimal techniques the skin dose is smaller than 2 mR and the gonadal doses lie around 0.1 mR for both male and female patients. An estimate of the dose burden from undesired radiation is appended."} {"id": "PMID:155583", "title": "[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)].", "content": "The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed.", "contents": "[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)]. The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed."} {"id": "PMID:155590", "title": "Reflux of metrizamide into the lateral ventricles in vomiting.", "content": "Two cases are presented in which metrizamide refluxed into the lateral ventricles after vomiting, the contrast having been brought in intrathecally by lumbar route for CT-scanning of the basal cisterns. It is suggested the intrathoracic and intraabdominal pressures transority achieved in vomiting are transmitted to the spinal canal through the vertebral venous plexus. This results in a pressure which is transmitted through the C.S.F. to the posterior fossa, and from there, for anatomical reasons, to the ventricular system. Transitory dilatation of the ventricles results in aspiration fluid from the fourth ventricle, and hence reversal of normal flow in the aqueduct of Sylvius.", "contents": "Reflux of metrizamide into the lateral ventricles in vomiting. Two cases are presented in which metrizamide refluxed into the lateral ventricles after vomiting, the contrast having been brought in intrathecally by lumbar route for CT-scanning of the basal cisterns. It is suggested the intrathoracic and intraabdominal pressures transority achieved in vomiting are transmitted to the spinal canal through the vertebral venous plexus. This results in a pressure which is transmitted through the C.S.F. to the posterior fossa, and from there, for anatomical reasons, to the ventricular system. Transitory dilatation of the ventricles results in aspiration fluid from the fourth ventricle, and hence reversal of normal flow in the aqueduct of Sylvius."} {"id": "PMID:155591", "title": "[Real time demonstration of the carotid and other peripheral arteries by ultrasound (echo arteriography) (author's transl)].", "content": "A newly developed ultrasound apparatus for use in angiologic diagnosis is described. The apparatus is a real time scanner with significantly better resolution than commercially available scanners. The carotid artery in the neck and major arteries in the arms and legs can be traced well into the periphery. An extremity can be examined in about ten minutes. It is possible to estimate the diameter of the vessel, the border between wall and lumen, its branches, amplitude and rhythm of pulsation and the relationship between the artery and its neighbouring tissues. The procedure is painless, has no side effects and therefore can be repeated as often as necessary.", "contents": "[Real time demonstration of the carotid and other peripheral arteries by ultrasound (echo arteriography) (author's transl)]. A newly developed ultrasound apparatus for use in angiologic diagnosis is described. The apparatus is a real time scanner with significantly better resolution than commercially available scanners. The carotid artery in the neck and major arteries in the arms and legs can be traced well into the periphery. An extremity can be examined in about ten minutes. It is possible to estimate the diameter of the vessel, the border between wall and lumen, its branches, amplitude and rhythm of pulsation and the relationship between the artery and its neighbouring tissues. The procedure is painless, has no side effects and therefore can be repeated as often as necessary."} {"id": "PMID:155592", "title": "Coarctation of the abdominal aorta.", "content": "Coarctation of the abdominal aorta is an uncommon process but an important cause of systemic hypertension. Angiography is the investigation of choice to establish a diagnosis and document the extent of involvement. However, angiography does not provide an etiological diagnosis; and it may not be possible to distinguish an acquired coarctation from a congenital process. Three patients with coarctation of the abdominal aorta are presented.", "contents": "Coarctation of the abdominal aorta. Coarctation of the abdominal aorta is an uncommon process but an important cause of systemic hypertension. Angiography is the investigation of choice to establish a diagnosis and document the extent of involvement. However, angiography does not provide an etiological diagnosis; and it may not be possible to distinguish an acquired coarctation from a congenital process. Three patients with coarctation of the abdominal aorta are presented."} {"id": "PMID:155593", "title": "[Arterio-venous angioma of the kidney: embolisation and two year follow-up (author's transl)].", "content": "Successful embolisation of an arteriovenous angioma of the kidney with gel foam suspension is described, with a two year follow-up. Embolisation cured hypertension, which had otherwise resisted treatment, and stopped haematuria. The need for careful follow-up is stressed with long-term observations using both angiography and scintigraphy of the affected kidney. The intra-arterial embolisation with gel foam resulted in a redistribution of blood-flow which led to complete success of treatment even thought the vascular malformation had not been totally obliterated.", "contents": "[Arterio-venous angioma of the kidney: embolisation and two year follow-up (author's transl)]. Successful embolisation of an arteriovenous angioma of the kidney with gel foam suspension is described, with a two year follow-up. Embolisation cured hypertension, which had otherwise resisted treatment, and stopped haematuria. The need for careful follow-up is stressed with long-term observations using both angiography and scintigraphy of the affected kidney. The intra-arterial embolisation with gel foam resulted in a redistribution of blood-flow which led to complete success of treatment even thought the vascular malformation had not been totally obliterated."} {"id": "PMID:155595", "title": "[The effect of contrast volume on the radiographic demonstration of the gall bladder and bile duct (author's transl)].", "content": "No differences could be detected subjectively in the quality of cholangiograms after the use of varying amounts of contrast medium (20 and 30 ml iodoxaminic acid). Pharmacolinetic data which would indicate the use of either quantity are not available. Densitometric measurements carried out by us showed no significant statistical difference between the results of using 20 or 30 ml iodoxaminic acid.", "contents": "[The effect of contrast volume on the radiographic demonstration of the gall bladder and bile duct (author's transl)]. No differences could be detected subjectively in the quality of cholangiograms after the use of varying amounts of contrast medium (20 and 30 ml iodoxaminic acid). Pharmacolinetic data which would indicate the use of either quantity are not available. Densitometric measurements carried out by us showed no significant statistical difference between the results of using 20 or 30 ml iodoxaminic acid."} {"id": "PMID:155596", "title": "[Improvement of oral cholecystography and cholangiography with ceruletid (author's transl)].", "content": "Following oral cholecystography in 100 patients, the conventional \"fatty meal\" was replaced by an intramuscular injection of Ceruletid in a dose of 0.4 microgram/kg body weight. The synthetic decapetide Ceruletid is a substance with a hormone-like effect on the gastro-intestinal tract. It contracts smooth muscle in the gut and stimulates secretion in the stomach and the exocrine pancreas. Compared with other substances producing contraction which are given orally, Ceruletid acts more quickly and more powerfully in producing contraction of the gall bladder muscle. In 86% of positive cholecystograms, this resulted in satisfactory demonstration of the bile duct, 66% better than for oral substances. Many abnormalities, particularly localised adenomyomatosis, can only be diagnosed after good contraction of the gall bladder. Side effects, such as nausea, dizziness and a feeling of heat were transitory. In three patients it led to vomiting. The rapid and certain effect of Ceruletid during oral cholecystography requires reassessment of the role of intravenous cholangiography in diagnosis. Particularly amongst out-patients, with a high proportion of normal gall bladders, it is possible to complete the examination in one stage by demonstrating the bile duct with Ceruletid.", "contents": "[Improvement of oral cholecystography and cholangiography with ceruletid (author's transl)]. Following oral cholecystography in 100 patients, the conventional \"fatty meal\" was replaced by an intramuscular injection of Ceruletid in a dose of 0.4 microgram/kg body weight. The synthetic decapetide Ceruletid is a substance with a hormone-like effect on the gastro-intestinal tract. It contracts smooth muscle in the gut and stimulates secretion in the stomach and the exocrine pancreas. Compared with other substances producing contraction which are given orally, Ceruletid acts more quickly and more powerfully in producing contraction of the gall bladder muscle. In 86% of positive cholecystograms, this resulted in satisfactory demonstration of the bile duct, 66% better than for oral substances. Many abnormalities, particularly localised adenomyomatosis, can only be diagnosed after good contraction of the gall bladder. Side effects, such as nausea, dizziness and a feeling of heat were transitory. In three patients it led to vomiting. The rapid and certain effect of Ceruletid during oral cholecystography requires reassessment of the role of intravenous cholangiography in diagnosis. Particularly amongst out-patients, with a high proportion of normal gall bladders, it is possible to complete the examination in one stage by demonstrating the bile duct with Ceruletid."} {"id": "PMID:155597", "title": "[The diagnosis and treatment of malignant haemangiopericytomas (author's transl)].", "content": "Two cases of malignant haemangiopericytomas are described; one was a multiple tumour, the other arose from the mediastinum. The difficulties of diagnosis, and particularly differentiation from lymphangiopericytoma, are stressed. Irradiation of the tumour is a useful addition to the forms of treatment.", "contents": "[The diagnosis and treatment of malignant haemangiopericytomas (author's transl)]. Two cases of malignant haemangiopericytomas are described; one was a multiple tumour, the other arose from the mediastinum. The difficulties of diagnosis, and particularly differentiation from lymphangiopericytoma, are stressed. Irradiation of the tumour is a useful addition to the forms of treatment."} {"id": "PMID:155598", "title": "[Radiographic examination of tracheal strictures by means of powdered tantalum (author's transl)].", "content": "This report deals with the diagnostic value of a tracheobronchography with powdered Tantalum in 5 patients who suffer from a severe stricture of the trachea. The own experiences with this method are described.", "contents": "[Radiographic examination of tracheal strictures by means of powdered tantalum (author's transl)]. This report deals with the diagnostic value of a tracheobronchography with powdered Tantalum in 5 patients who suffer from a severe stricture of the trachea. The own experiences with this method are described."} {"id": "PMID:155599", "title": "[Gynaecomastia and mammography (author's transl)].", "content": "The term gynaecomastia indicates an increase in the mass of the normally rudimentary male breast; morphologically there is hyperplasia and differentiation of the epithelial and mesenchymal breast components. Gynaecomastia is not a disease in itself, but a symptom of some underlying disease or the result of drugs. Of 2895 breast operations performed at the surgical clinic of the University of G\u00f6ttingen, 2.97% were operations on men with gynaecomastia. Amongst 79222 mammograms in the Radiological Clinic of the University, there were 900 mammograms (1.14%) of 392 men with gynaecomastia. Most benign and malignant conditions in men are retromammary in localisation. For this reason clinical evaluation is frequently wrong. The use of mammography as an additional diagnostic method in men is therefore more important than it is in women. Systematic analysis of the mammograms performed on men has made possible a classification of gynaecomastia according to the radiological appearances: I Septal linear structures (8.5%), II Opacities of varying density and size (26.5%), III Circular, usually inhomogenous shadows (15.5%), IV Homogeneous, demarcated foci of varying size (35.5%), V Soft-tissue hyperplasia-pseudo-gynaecomastia (10%).", "contents": "[Gynaecomastia and mammography (author's transl)]. The term gynaecomastia indicates an increase in the mass of the normally rudimentary male breast; morphologically there is hyperplasia and differentiation of the epithelial and mesenchymal breast components. Gynaecomastia is not a disease in itself, but a symptom of some underlying disease or the result of drugs. Of 2895 breast operations performed at the surgical clinic of the University of G\u00f6ttingen, 2.97% were operations on men with gynaecomastia. Amongst 79222 mammograms in the Radiological Clinic of the University, there were 900 mammograms (1.14%) of 392 men with gynaecomastia. Most benign and malignant conditions in men are retromammary in localisation. For this reason clinical evaluation is frequently wrong. The use of mammography as an additional diagnostic method in men is therefore more important than it is in women. Systematic analysis of the mammograms performed on men has made possible a classification of gynaecomastia according to the radiological appearances: I Septal linear structures (8.5%), II Opacities of varying density and size (26.5%), III Circular, usually inhomogenous shadows (15.5%), IV Homogeneous, demarcated foci of varying size (35.5%), V Soft-tissue hyperplasia-pseudo-gynaecomastia (10%)."} {"id": "PMID:155600", "title": "[The diagnostic significance of microcalcifications in testicular tumors (author's transl)].", "content": "The evaluation of total orchiectomy tissue specimens with malignant testicular tumors shows that microcalcifications can be found in a surprisingly high percentage by radiological and histological examinations. Small, often in several groups located calcifications in the parenchyma neighbouring the tumor are typical for seminoma, whereas in teratoma solitary microcalcifications and polymorphic types can also be seen. Microcalcifications are also present in not neoplastic testicular diseases but in a much smaller percentage and with a different type of calcification. The preoperative radiographic examination of testicular tumors of unknown origin seems to be indicated as a non-invasive method able to provide further information about the presence of a malignant germ cell tumor. Regarding the genetic risks of the method, there is hope to avoid other more invasive examinations with their danger of tumor spreading and to enable a radical resection of the primary tumor before its metastic formation by the mean of preoperative orchioradiography.", "contents": "[The diagnostic significance of microcalcifications in testicular tumors (author's transl)]. The evaluation of total orchiectomy tissue specimens with malignant testicular tumors shows that microcalcifications can be found in a surprisingly high percentage by radiological and histological examinations. Small, often in several groups located calcifications in the parenchyma neighbouring the tumor are typical for seminoma, whereas in teratoma solitary microcalcifications and polymorphic types can also be seen. Microcalcifications are also present in not neoplastic testicular diseases but in a much smaller percentage and with a different type of calcification. The preoperative radiographic examination of testicular tumors of unknown origin seems to be indicated as a non-invasive method able to provide further information about the presence of a malignant germ cell tumor. Regarding the genetic risks of the method, there is hope to avoid other more invasive examinations with their danger of tumor spreading and to enable a radical resection of the primary tumor before its metastic formation by the mean of preoperative orchioradiography."} {"id": "PMID:155601", "title": "[Polysegmental andersson lesion in ankylosing spondylitis (roentgenological-histological synopsis) (author's transl)].", "content": "Basing on roentgenological observation of the course of the disease, and on postmortem examination, of a patient with polysegmental Andersson lesions (known as spondylodiscitis) in ankylosing spondylitis, the article reports on the histological and often also clinico-roentgenological possibility of differentiating between an inflammatory and non-inflammatory type of this destructive lesion. The non-inflammatory type of Andersson lesion reflects a fracture due to fatigue, or its sequel, eg pseudarthrosis, in the stiffened axial skeleton. In this particular patient, renal osteopathy had favoured the genesis of the disease.", "contents": "[Polysegmental andersson lesion in ankylosing spondylitis (roentgenological-histological synopsis) (author's transl)]. Basing on roentgenological observation of the course of the disease, and on postmortem examination, of a patient with polysegmental Andersson lesions (known as spondylodiscitis) in ankylosing spondylitis, the article reports on the histological and often also clinico-roentgenological possibility of differentiating between an inflammatory and non-inflammatory type of this destructive lesion. The non-inflammatory type of Andersson lesion reflects a fracture due to fatigue, or its sequel, eg pseudarthrosis, in the stiffened axial skeleton. In this particular patient, renal osteopathy had favoured the genesis of the disease."} {"id": "PMID:155602", "title": "[Comments on the problem of non-specific sclerosing spondylodiscitides (author's transl)].", "content": "After reviewing types of sclerosis of the vertebral bodies and spondylodiscitides occurring near the vertebral discs, the causes of which are relatively well known, two observations of cases of chronic progressive sclerosing spondylodiscitis are described in detail together with their case history. The primary manifestation (in the lumbar vertebral column) is seen, apart from a discitis, in a relatively early and eventually homogeneous sclerosing of the spongiosa. The course of the disease is extremely protracted; after 1-5 years, other parts of the vertebral column are affected in a similar manner. Inflammatory parameters are definitely involved, and the nosological neighbourhood to angylosing spondylitis is discussed. In the absence of any other hints, it appears justified to assume non-specific chronic progressive sclerosing spondylodiscitis which begins monostotically and can proceed according to a polystotic pattern.", "contents": "[Comments on the problem of non-specific sclerosing spondylodiscitides (author's transl)]. After reviewing types of sclerosis of the vertebral bodies and spondylodiscitides occurring near the vertebral discs, the causes of which are relatively well known, two observations of cases of chronic progressive sclerosing spondylodiscitis are described in detail together with their case history. The primary manifestation (in the lumbar vertebral column) is seen, apart from a discitis, in a relatively early and eventually homogeneous sclerosing of the spongiosa. The course of the disease is extremely protracted; after 1-5 years, other parts of the vertebral column are affected in a similar manner. Inflammatory parameters are definitely involved, and the nosological neighbourhood to angylosing spondylitis is discussed. In the absence of any other hints, it appears justified to assume non-specific chronic progressive sclerosing spondylodiscitis which begins monostotically and can proceed according to a polystotic pattern."} {"id": "PMID:155603", "title": "[The importance of scintimetry in the differential diagnosis of roentgenological areas of increased \"translucence\" in the skeleton of children (author's transl)].", "content": "A random selection of lesions representing osteolytic bone processes was evaluated with the \"region-of-interest\" technique in order to determine whether scintimetry can be helpful in the differential diagnosis of such processes in children. Bone tumours with structural densification, as well as osteomyelitides, were reviewed for comparative purposes. It was found that scintigraphy of the skeleton, while supplying additional and clinically quite interesting information, does not make any substantial contribution to the differential diagnostic clarification of roentgenological translucence in the skeleton of children.", "contents": "[The importance of scintimetry in the differential diagnosis of roentgenological areas of increased \"translucence\" in the skeleton of children (author's transl)]. A random selection of lesions representing osteolytic bone processes was evaluated with the \"region-of-interest\" technique in order to determine whether scintimetry can be helpful in the differential diagnosis of such processes in children. Bone tumours with structural densification, as well as osteomyelitides, were reviewed for comparative purposes. It was found that scintigraphy of the skeleton, while supplying additional and clinically quite interesting information, does not make any substantial contribution to the differential diagnostic clarification of roentgenological translucence in the skeleton of children."} {"id": "PMID:155604", "title": "[A comparison of the side effects of water-soluble contrast media for lumbar myelography (author's transl)].", "content": "A prospective comparison study of the water-soluble contrast media Amipaque and Dimer-X was performed on 200 lumbar myelograms. During this investigation, and amongst a total of 1702 myelograms with Dimer-X, there were only transient mild side effects; these were somewhat more common with Amipaque. There were no sequelae, particularly those of a neurological nature. After careful clinical examination, and by observing certain precautionary measures, it is possible to perform lumbar myelography with water-soluble contrast media on an out-patient basis.", "contents": "[A comparison of the side effects of water-soluble contrast media for lumbar myelography (author's transl)]. A prospective comparison study of the water-soluble contrast media Amipaque and Dimer-X was performed on 200 lumbar myelograms. During this investigation, and amongst a total of 1702 myelograms with Dimer-X, there were only transient mild side effects; these were somewhat more common with Amipaque. There were no sequelae, particularly those of a neurological nature. After careful clinical examination, and by observing certain precautionary measures, it is possible to perform lumbar myelography with water-soluble contrast media on an out-patient basis."} {"id": "PMID:155605", "title": "[Conventional-radiographic and computer-assisted cisternography of the posterior fossa with metrizamide (author's transl)].", "content": "Conventional radiographic and computer-assisted (CT) cisternography of the posterior fossa using Metrizamide was carried out in 25 and 33 patients respectively. The contrast medium was injected by the lumbar or cervical route. During conventional cisternography, contrast medium distribution is most easily controlled by a lateral injection at the level of the first to second cervical vertebra. Because of its physical properties, Metrizamide results in good demonstration of detail. CT cisternography is usually able to demonstrate an extra-cerebral space-occupying lesion with a diameter greater than 1 cm. This procedure has fewer complications due to the contrast medium or the technique, since small amounts of Metrizamide achieve an adequate increase in the density of the CSF; it is therefore possible to inject this by a lumbar route and to carry out the entire examination with the patient supine. Both conventional and CT cisternography permit very accurate diagnosis in the region of the foramen magnum. Both procedures can be used on their own or as an addition to conventional Metrizamide myelography.", "contents": "[Conventional-radiographic and computer-assisted cisternography of the posterior fossa with metrizamide (author's transl)]. Conventional radiographic and computer-assisted (CT) cisternography of the posterior fossa using Metrizamide was carried out in 25 and 33 patients respectively. The contrast medium was injected by the lumbar or cervical route. During conventional cisternography, contrast medium distribution is most easily controlled by a lateral injection at the level of the first to second cervical vertebra. Because of its physical properties, Metrizamide results in good demonstration of detail. CT cisternography is usually able to demonstrate an extra-cerebral space-occupying lesion with a diameter greater than 1 cm. This procedure has fewer complications due to the contrast medium or the technique, since small amounts of Metrizamide achieve an adequate increase in the density of the CSF; it is therefore possible to inject this by a lumbar route and to carry out the entire examination with the patient supine. Both conventional and CT cisternography permit very accurate diagnosis in the region of the foramen magnum. Both procedures can be used on their own or as an addition to conventional Metrizamide myelography."} {"id": "PMID:155606", "title": "[Image characteristics of the computer tomograph (author's transl)].", "content": "In the present paper the images produced by spheres of varying diameter (d = 4,6,8,10 mm) embedded in a homogeneous substance of varying densities (H' = 3,48,93,137 Hounsfield units) as produced by computer tomography were studied. Measurements show that for each sphere diameter there is a minimum contrast between the substance of the sphere and its surroundings which must exist in order to show this sphere by computer tomography. It was also shown that the partial volume effect is of significance for the attenuation of the spheres. The effect of the position of the spheres within the slices to be imaged was studied. The results clearly indicate that in the investigation of small tissue changes in the body, the thickness of the slice and patient displacement should be kept as small as possible.", "contents": "[Image characteristics of the computer tomograph (author's transl)]. In the present paper the images produced by spheres of varying diameter (d = 4,6,8,10 mm) embedded in a homogeneous substance of varying densities (H' = 3,48,93,137 Hounsfield units) as produced by computer tomography were studied. Measurements show that for each sphere diameter there is a minimum contrast between the substance of the sphere and its surroundings which must exist in order to show this sphere by computer tomography. It was also shown that the partial volume effect is of significance for the attenuation of the spheres. The effect of the position of the spheres within the slices to be imaged was studied. The results clearly indicate that in the investigation of small tissue changes in the body, the thickness of the slice and patient displacement should be kept as small as possible."} {"id": "PMID:155607", "title": "[Computer tomographic longitudinal sections of the trunk reconstructed from standard cross-sections (author's transl)].", "content": "Reduction in scan times and advances in the field of image reconstruction have made it possible to reconstruct the trunk from sequential coronal sections. For this purpose 8 mm cuts without overlap are suitable. There is consequently no increase in patient dose or in the scan time. Longitudinal sections can be reconstructed by a dedicated computer in about 10 minutes and cross sections can be evaluated in more detail. The longitudinal reconstructions provide better demonstration of organs and space-occupying lesions in their craniocaudal extent. This extension of the diagnostic spectrum is of value to the diagnostician and particularly to radiotherapists and surgeons during treatment planning.", "contents": "[Computer tomographic longitudinal sections of the trunk reconstructed from standard cross-sections (author's transl)]. Reduction in scan times and advances in the field of image reconstruction have made it possible to reconstruct the trunk from sequential coronal sections. For this purpose 8 mm cuts without overlap are suitable. There is consequently no increase in patient dose or in the scan time. Longitudinal sections can be reconstructed by a dedicated computer in about 10 minutes and cross sections can be evaluated in more detail. The longitudinal reconstructions provide better demonstration of organs and space-occupying lesions in their craniocaudal extent. This extension of the diagnostic spectrum is of value to the diagnostician and particularly to radiotherapists and surgeons during treatment planning."} {"id": "PMID:155610", "title": "Is there a future for single photon emission tomography?", "content": "Emission tomography has the potential to be developed into a clinically useful technique. Its clinical applications, however, will be limited and not in the main stream of space occupying disease detection but in the definition of quantitative information particularly relevant in those disease processes where the metabolic component is the most important one. Special purpose designed instrumentation may prove to be the best of several possible compromises.", "contents": "Is there a future for single photon emission tomography? Emission tomography has the potential to be developed into a clinically useful technique. Its clinical applications, however, will be limited and not in the main stream of space occupying disease detection but in the definition of quantitative information particularly relevant in those disease processes where the metabolic component is the most important one. Special purpose designed instrumentation may prove to be the best of several possible compromises."} {"id": "PMID:155616", "title": "[Computer tomography in acute pancreatitis (author's transl)].", "content": "The computer tomographic appearances of acute pancreatitis have been analysed 33 patients. It is usually a simple matter to distinguish between the acute, oedematous pancreatitis, which can be treated conservatively, and the suppurative pancreatitis with haemorrhagic and necrotising features, which require surgical exploration.", "contents": "[Computer tomography in acute pancreatitis (author's transl)]. The computer tomographic appearances of acute pancreatitis have been analysed 33 patients. It is usually a simple matter to distinguish between the acute, oedematous pancreatitis, which can be treated conservatively, and the suppurative pancreatitis with haemorrhagic and necrotising features, which require surgical exploration."} {"id": "PMID:155617", "title": "[Computerized tomography of the liver. Accuracy of the method in biopsy proven diagnoses (author's transl)].", "content": "To evaluate the diagnostic accuracy of computerized tomography (CT) in detecting liver disease, CT-findings of 320 patients examined with a slow CT-scanner (2.5 min scanning time/slice) could be compared to the results of bioptic procedures. Sensitivity was 81% for circumscript liver disease, specificity was 85%. In 69% of the cases, a type-specific diagnosis of circumscript liver diseases was possible, this percentage increased by 5% if patients with a true-positive differential diagnosis were included. 73% of the patients with liver metastases were correctly identified to have metastatic liver disease. Obstructive jaundice was correctly identified in 77% and correctly excluded in all patients with medical jaundice. For a large variety of hepatocellular disease, ratio of true positive diagnoses was 16% only. The value of CT in hepatocellular disease concerns exclusion of presumed space-occupying lesions. In a control group of 310 patients with only \"clinically\" and not bioptically confirmed diagnoses, specificity was 96% and sensitivity concerning focal liver disease was 82%. Our results prove CT to be a valuable non-invasive tool in the evaluation of circumscript liver disease.", "contents": "[Computerized tomography of the liver. Accuracy of the method in biopsy proven diagnoses (author's transl)]. To evaluate the diagnostic accuracy of computerized tomography (CT) in detecting liver disease, CT-findings of 320 patients examined with a slow CT-scanner (2.5 min scanning time/slice) could be compared to the results of bioptic procedures. Sensitivity was 81% for circumscript liver disease, specificity was 85%. In 69% of the cases, a type-specific diagnosis of circumscript liver diseases was possible, this percentage increased by 5% if patients with a true-positive differential diagnosis were included. 73% of the patients with liver metastases were correctly identified to have metastatic liver disease. Obstructive jaundice was correctly identified in 77% and correctly excluded in all patients with medical jaundice. For a large variety of hepatocellular disease, ratio of true positive diagnoses was 16% only. The value of CT in hepatocellular disease concerns exclusion of presumed space-occupying lesions. In a control group of 310 patients with only \"clinically\" and not bioptically confirmed diagnoses, specificity was 96% and sensitivity concerning focal liver disease was 82%. Our results prove CT to be a valuable non-invasive tool in the evaluation of circumscript liver disease."} {"id": "PMID:155618", "title": "[Computer-cardio-tomography in idiopathic hypertrophic subvalvular aortic stenosis--a new contribution to non-invasive diagnosis (author's transl)].", "content": "The use of computer tomography as a non-invasive procedure in the diagnosis of idiopathic hypertrophic subvalvular aortic stenosis is described. Seven patients were investigated in whom the diagnosis had been confirmed by echocardiography and laevocardiography with pressure measurements. Details of the method are discussed and computer tomography and echocardiography are compared. The features of greatest differential diagnostic importance relating to asymmetrical septum hypertrophy are discussed.", "contents": "[Computer-cardio-tomography in idiopathic hypertrophic subvalvular aortic stenosis--a new contribution to non-invasive diagnosis (author's transl)]. The use of computer tomography as a non-invasive procedure in the diagnosis of idiopathic hypertrophic subvalvular aortic stenosis is described. Seven patients were investigated in whom the diagnosis had been confirmed by echocardiography and laevocardiography with pressure measurements. Details of the method are discussed and computer tomography and echocardiography are compared. The features of greatest differential diagnostic importance relating to asymmetrical septum hypertrophy are discussed."} {"id": "PMID:155619", "title": "[Computer tomographic demonstration of the popliteal artery entrapment syndrome (author's transl)].", "content": "The popliteal artery entrapment syndrome can be diagnosed by computer tomography with a greater degree of certainty than by angiography. The advantage of computer tomography depends on the simultaneous demonstration of the position of the vessel and of the surrounding muscles and their abnormal situation.", "contents": "[Computer tomographic demonstration of the popliteal artery entrapment syndrome (author's transl)]. The popliteal artery entrapment syndrome can be diagnosed by computer tomography with a greater degree of certainty than by angiography. The advantage of computer tomography depends on the simultaneous demonstration of the position of the vessel and of the surrounding muscles and their abnormal situation."} {"id": "PMID:155620", "title": "[Radiological and scintigraphic evaluation of hip prostheses (author's transl)].", "content": "The radiological findings following the introduction of hip prostheses are often equivocal. Additional bone scintigrams often provide important information for the evaluation of the prostheses. 1. An unstable hip prosthesis is characterised by abnormal uptake in bone, due to static and mechanical stress. 2. A positive scintigram does not necessarily indicate instability of the prosthesis. Increased uptake may also be due to inflammatory bone changes, healing, bone replacement, abnormal local stresses or soft tissue calcification. 3. In evaluating the scintigram one must take account not only of the intensity of isotope uptake, but also its distribution and exact localisation. 4. It is essential to compare the scintigram with the radiograph. Radiological features of possible instability become diagnostic if they correspond to appropriate increased radioactivity. If the latter is absent, the of instability remains doubtful. 5. In some cases early loosening of the stem of the prosthesis can be diagnosed while the radiograph is still negative. Increased radioactivity in the acetabulum is frequently seen in the presence of a stable acetabular prosthesis and must be interpreted with caution as a sign of loosening of the prosthesis.", "contents": "[Radiological and scintigraphic evaluation of hip prostheses (author's transl)]. The radiological findings following the introduction of hip prostheses are often equivocal. Additional bone scintigrams often provide important information for the evaluation of the prostheses. 1. An unstable hip prosthesis is characterised by abnormal uptake in bone, due to static and mechanical stress. 2. A positive scintigram does not necessarily indicate instability of the prosthesis. Increased uptake may also be due to inflammatory bone changes, healing, bone replacement, abnormal local stresses or soft tissue calcification. 3. In evaluating the scintigram one must take account not only of the intensity of isotope uptake, but also its distribution and exact localisation. 4. It is essential to compare the scintigram with the radiograph. Radiological features of possible instability become diagnostic if they correspond to appropriate increased radioactivity. If the latter is absent, the of instability remains doubtful. 5. In some cases early loosening of the stem of the prosthesis can be diagnosed while the radiograph is still negative. Increased radioactivity in the acetabulum is frequently seen in the presence of a stable acetabular prosthesis and must be interpreted with caution as a sign of loosening of the prosthesis."} {"id": "PMID:155621", "title": "[Baker cysts: an accompaniment of chronic diseases of the knee joint (author's transl)].", "content": "One hundred and twenty one Baker cysts demonstrated by arthrography have been analysed. Morphologically one must distinguish between distension cysts and dissection cysts. Distension cysts are more common with various diseases of the knee joint (68% of all cysts). Dissection cysts (32%) are found particularly with inflammatory-rheumatic diseases and are rarely of degenerative or post-traumatic origin. Acute rupture of the cyst was observed on ten occasions. Repeated rupture, which had only been suspected previously, was demonstrated by arthrography in four patients. It is pointed out that Baker cysts may imitate the features of acute thrombophlebitis.", "contents": "[Baker cysts: an accompaniment of chronic diseases of the knee joint (author's transl)]. One hundred and twenty one Baker cysts demonstrated by arthrography have been analysed. Morphologically one must distinguish between distension cysts and dissection cysts. Distension cysts are more common with various diseases of the knee joint (68% of all cysts). Dissection cysts (32%) are found particularly with inflammatory-rheumatic diseases and are rarely of degenerative or post-traumatic origin. Acute rupture of the cyst was observed on ten occasions. Repeated rupture, which had only been suspected previously, was demonstrated by arthrography in four patients. It is pointed out that Baker cysts may imitate the features of acute thrombophlebitis."} {"id": "PMID:155622", "title": "[Gardner's syndrome. three patients with varying manifestations (author's transl)].", "content": "Fully developed Gardner's syndrome is characterised by the triad of intestinal polyposis, osteomas and multiple soft tissue tumours. Absence of any one of these manifestations results in a bisymptomatic form. We describe three patients, one woman and two men aged 40, 46 and 51 years. In two patients the triad was fully expressed, but with varying organ involvement. The third patient was of the bisymptomatic type with osseous and intestinal lesions.", "contents": "[Gardner's syndrome. three patients with varying manifestations (author's transl)]. Fully developed Gardner's syndrome is characterised by the triad of intestinal polyposis, osteomas and multiple soft tissue tumours. Absence of any one of these manifestations results in a bisymptomatic form. We describe three patients, one woman and two men aged 40, 46 and 51 years. In two patients the triad was fully expressed, but with varying organ involvement. The third patient was of the bisymptomatic type with osseous and intestinal lesions."} {"id": "PMID:155623", "title": "[The clinical and radiological picture of degenerative disease of the extra- and intra-cranial vessels (author's transl)].", "content": "The clinical and angiograms of 500 patients with degenerative disease of their cerebral vessels were evaluated. The clinical severity of the ischaemic changes was graded and compared with localisation and extent of the angiographic abnormality. In these patients there is an increased risk during angiography and a careful technique has to be employed. Two examples are used to show that it is possible to clarify even complex neurological and angiographic problems by means of an appropriate technique, 90% of our patients with a definite cerebral infarct gave a history of previous transitory ischaemic attacks. In our opinion patients with these attacks are of particular interest to the angiographer and the surgeon.", "contents": "[The clinical and radiological picture of degenerative disease of the extra- and intra-cranial vessels (author's transl)]. The clinical and angiograms of 500 patients with degenerative disease of their cerebral vessels were evaluated. The clinical severity of the ischaemic changes was graded and compared with localisation and extent of the angiographic abnormality. In these patients there is an increased risk during angiography and a careful technique has to be employed. Two examples are used to show that it is possible to clarify even complex neurological and angiographic problems by means of an appropriate technique, 90% of our patients with a definite cerebral infarct gave a history of previous transitory ischaemic attacks. In our opinion patients with these attacks are of particular interest to the angiographer and the surgeon."} {"id": "PMID:155624", "title": "[Partial aplasia of the right internal carotid artery with an unusual collateral circulation below the hypophysis (author's transl)].", "content": "A case of partial aplasia of the right internal carotid artery with an unusual artery passing through the skull base below the hypophysis is described. An association between the presence of this vessel and recurring abnormalities of eye movements with alternating ptosis is assumed. The ontogeny and phylogeny of this collateral artery are discussed.", "contents": "[Partial aplasia of the right internal carotid artery with an unusual collateral circulation below the hypophysis (author's transl)]. A case of partial aplasia of the right internal carotid artery with an unusual artery passing through the skull base below the hypophysis is described. An association between the presence of this vessel and recurring abnormalities of eye movements with alternating ptosis is assumed. The ontogeny and phylogeny of this collateral artery are discussed."} {"id": "PMID:155625", "title": "Areae gastricae and gastritis in double contrast barium meal.", "content": "The areae gastricae were studied in patients with different forms of gastritis and with normal gastric mucosa. The material consisted of 57 patients. First gastroscopy was done and biopsies were taken. The stomach was studied on the following day by the double contrast barium meal. The material was divided according to the gastroscopic and biopsy findings into the following groups: normal, superficial gastritis, mixed gastritis, and atrophic gastritis. In the analysis of the surface pattern, special attention was paid to the shape, size and defects of areae gastricae. Corpus and antrum were dealt with separately. In the normal material the areae gastricae were regular in shape, and the size was usually 1--3 mm. Irregular shape, bigger size and more frequent defect areas seemed to point to gastritis. Such changes were especially clear in atrophic gastritis. The significance of the areae gastricae in practice is discussed.", "contents": "Areae gastricae and gastritis in double contrast barium meal. The areae gastricae were studied in patients with different forms of gastritis and with normal gastric mucosa. The material consisted of 57 patients. First gastroscopy was done and biopsies were taken. The stomach was studied on the following day by the double contrast barium meal. The material was divided according to the gastroscopic and biopsy findings into the following groups: normal, superficial gastritis, mixed gastritis, and atrophic gastritis. In the analysis of the surface pattern, special attention was paid to the shape, size and defects of areae gastricae. Corpus and antrum were dealt with separately. In the normal material the areae gastricae were regular in shape, and the size was usually 1--3 mm. Irregular shape, bigger size and more frequent defect areas seemed to point to gastritis. Such changes were especially clear in atrophic gastritis. The significance of the areae gastricae in practice is discussed."} {"id": "PMID:155626", "title": "[Hypernephroma in a pelvic kidney. Diagnostic problems during angiography (author's transl)].", "content": "A hypernephroma in a pelvic kidney of a 54-year-old patient is described, which could not be demonstrated angiographically. This is explained by marked compression of the kidney because of the limited available space and the pressure of the surrounding organs. There was also histological proof of advanced intimal fibrosis in the artery and extensive obstruction of the vein by tumour, leading to diminished circulation of blood. The extreme rarity of hypernephromas in pelvic kidneys is stressed; this is barely mentioned in the literature.", "contents": "[Hypernephroma in a pelvic kidney. Diagnostic problems during angiography (author's transl)]. A hypernephroma in a pelvic kidney of a 54-year-old patient is described, which could not be demonstrated angiographically. This is explained by marked compression of the kidney because of the limited available space and the pressure of the surrounding organs. There was also histological proof of advanced intimal fibrosis in the artery and extensive obstruction of the vein by tumour, leading to diminished circulation of blood. The extreme rarity of hypernephromas in pelvic kidneys is stressed; this is barely mentioned in the literature."} {"id": "PMID:155627", "title": "[Sonography, computer tomography and angiography in the diagnosis of an haemangioma of the renal pelvis (author's transl)].", "content": "A renal pelvis haemangioma is described, which was diagnosed by means of sonography and angiography. The angiographic criteria are enumerated. The sonographic findings have not previously been described. Their value in the diagnosis, and in differential diagnosis, is discussed.", "contents": "[Sonography, computer tomography and angiography in the diagnosis of an haemangioma of the renal pelvis (author's transl)]. A renal pelvis haemangioma is described, which was diagnosed by means of sonography and angiography. The angiographic criteria are enumerated. The sonographic findings have not previously been described. Their value in the diagnosis, and in differential diagnosis, is discussed."} {"id": "PMID:155628", "title": "[Percutaneous nephropyelostomy in children (author's transl)].", "content": "Percutaneous nephropyelostomy with a fine needle technique was performed successfully in 20 out of 21 children with urinary tract obstruction. The procedure was of value in assessing the recovery of renal function and for measuring perfusion pressure. As a therapeutic measure the method was used to preoperatively in children who were severly ill, and post-operatively for the treatment of complications after surgery on the urinary tract. A complication seen in two children was repeated dislodgement of the catheter.", "contents": "[Percutaneous nephropyelostomy in children (author's transl)]. Percutaneous nephropyelostomy with a fine needle technique was performed successfully in 20 out of 21 children with urinary tract obstruction. The procedure was of value in assessing the recovery of renal function and for measuring perfusion pressure. As a therapeutic measure the method was used to preoperatively in children who were severly ill, and post-operatively for the treatment of complications after surgery on the urinary tract. A complication seen in two children was repeated dislodgement of the catheter."} {"id": "PMID:155629", "title": "Nonsurgical removal of intravascular foreign bodies.", "content": "With increasing use of indwelling venous catheters, embolization of intravascular catheter fragments has become a well-known complication. Because of the high risk and serious complications, embolized fragments should be retrieved whenever possible. Four cases of successful nonsurgical percutaneous catheter retrieval (two adults and two children) are described using a wire loop and a hook-shaped catheter technique. The method described allow a safe and rapid retrieval and should always precede surgical exploration.", "contents": "Nonsurgical removal of intravascular foreign bodies. With increasing use of indwelling venous catheters, embolization of intravascular catheter fragments has become a well-known complication. Because of the high risk and serious complications, embolized fragments should be retrieved whenever possible. Four cases of successful nonsurgical percutaneous catheter retrieval (two adults and two children) are described using a wire loop and a hook-shaped catheter technique. The method described allow a safe and rapid retrieval and should always precede surgical exploration."} {"id": "PMID:155630", "title": "[Transfemoral aspiration of a thrombus from a renal artery with an angiographic catheter (author's transl)].", "content": "Thrombosis in a renal artery occurred in a 60-year-old woman after regional hypothermia of the kidney for which balloon occlusion of the artery had been used. Perfusion of the kidney was re-established by aspiration and flushing of the thrombus; this was confirmed angiographically and anatomically. Renal function did not recover, however, since removal of the thrombus by means of an angiographic catheter was carried out too late. We regard early aspiration of emboli from major abdominal vessels as a further application of arterial catheterisation by the Seldinger technique.", "contents": "[Transfemoral aspiration of a thrombus from a renal artery with an angiographic catheter (author's transl)]. Thrombosis in a renal artery occurred in a 60-year-old woman after regional hypothermia of the kidney for which balloon occlusion of the artery had been used. Perfusion of the kidney was re-established by aspiration and flushing of the thrombus; this was confirmed angiographically and anatomically. Renal function did not recover, however, since removal of the thrombus by means of an angiographic catheter was carried out too late. We regard early aspiration of emboli from major abdominal vessels as a further application of arterial catheterisation by the Seldinger technique."} {"id": "PMID:155631", "title": "[Determination of the iodine content of the thyroid by means of fluorescence scans (author's transl)].", "content": "A procedure is described in which stable 127I in the thyroid is induced to fluorescence (28.5 keV) by 241Am (59.5 keV). The radiation is registered on a Si (Li) detector and can be used in order to obtain a scintigram or to determine the concentration of127I in the thyroid at any selected point. The apparatus is available commercially and has been adapted for use with a scanner. Measurements using collimation of 3.5 to 4 cm revealed a focus with a marked tomographic effect. The sensitivity of the apparatus was investigated by using solutions of varying iodine concentrations; calibration curves for determining iodine concentration in thyroid tissue were obtained. It is necessary to take account of the thickness of the thyroid gland and of the superficial tissues because of the marked attenuation of the radiation within the tissues. Radiation dose to the thyroid during the scintigram was about 0.1 mGy (10 mrd), i.e. about 5% of a conventional TC scintigram. There is no whole body irradiation.", "contents": "[Determination of the iodine content of the thyroid by means of fluorescence scans (author's transl)]. A procedure is described in which stable 127I in the thyroid is induced to fluorescence (28.5 keV) by 241Am (59.5 keV). The radiation is registered on a Si (Li) detector and can be used in order to obtain a scintigram or to determine the concentration of127I in the thyroid at any selected point. The apparatus is available commercially and has been adapted for use with a scanner. Measurements using collimation of 3.5 to 4 cm revealed a focus with a marked tomographic effect. The sensitivity of the apparatus was investigated by using solutions of varying iodine concentrations; calibration curves for determining iodine concentration in thyroid tissue were obtained. It is necessary to take account of the thickness of the thyroid gland and of the superficial tissues because of the marked attenuation of the radiation within the tissues. Radiation dose to the thyroid during the scintigram was about 0.1 mGy (10 mrd), i.e. about 5% of a conventional TC scintigram. There is no whole body irradiation."} {"id": "PMID:155632", "title": "[Reduction of radiation-induced late effects on vascular connective tissue of the skin (mouse paw) by o-(beta-hydroxyethyl)-rutoside].", "content": "The induction of irreversible late effects of the skin after irradiation of the mouse foot with and without i.p. HR-application has been investigated. The high protective effect of HR could be demonstrated which prevents grave late damage such as loss of toes. One single application of 300 mg/HR 0,5 h before irradiation has been optimally successful. Beside the excellent compatibility of even high doses, HR seems to have the advantage to be a selective radiation protection substance with a protective effect only for healthy cells (in this case presumably the vascular systems) and no effect on malignant cells. The possible mechanism of the stabilization of oxidative phosphorylation by flavonoids and a depression of glycolysis in malignant cells will be discussed.", "contents": "[Reduction of radiation-induced late effects on vascular connective tissue of the skin (mouse paw) by o-(beta-hydroxyethyl)-rutoside]. The induction of irreversible late effects of the skin after irradiation of the mouse foot with and without i.p. HR-application has been investigated. The high protective effect of HR could be demonstrated which prevents grave late damage such as loss of toes. One single application of 300 mg/HR 0,5 h before irradiation has been optimally successful. Beside the excellent compatibility of even high doses, HR seems to have the advantage to be a selective radiation protection substance with a protective effect only for healthy cells (in this case presumably the vascular systems) and no effect on malignant cells. The possible mechanism of the stabilization of oxidative phosphorylation by flavonoids and a depression of glycolysis in malignant cells will be discussed."} {"id": "PMID:155638", "title": "[Regression of diabetic glomerular changes following islet transplantation. A study of rats with streptozotocin diabetes].", "content": "The precise etiology and pathogenesis of diabetic glomerulosclerosis still remain obscure. The aim of the present study was 1. to evaluate the morphologic and functional alterations of mesangial cells in long term diabetic rats and 2. to study the effect of islet transplantation on these lesions. Diabetes was induced in inbred Lewis rats with streptozotocin (65 mg per kg). 7 month later glomeruli of diabetic rats showed hyaline nodular deposits, exsudative lesions and glomerular aneurysms. The thickening of the mesangium measured by point counting method was statistically significant compared with age matched controls. Large quantities of IgG, beta 1c and fibrinogen in a predominantly mesangial pattern could be demonstrated by fluorescence microscopy. After injection of aggregated immunoglobulin the uptake of IgG by the mesangial cells was delayed in the diabetics compared with normal controls. Islet transplantation resulted in a marked reduction of the light microscopic and immunohistological glomerular lesions and restored the phagocytic capacity of the mesangial cells almost completely. From these results it is concluded, that the fundamental defect in diabetic glomerulosclerosis is a metabolically induced functional defect of the mesangial cells.", "contents": "[Regression of diabetic glomerular changes following islet transplantation. A study of rats with streptozotocin diabetes]. The precise etiology and pathogenesis of diabetic glomerulosclerosis still remain obscure. The aim of the present study was 1. to evaluate the morphologic and functional alterations of mesangial cells in long term diabetic rats and 2. to study the effect of islet transplantation on these lesions. Diabetes was induced in inbred Lewis rats with streptozotocin (65 mg per kg). 7 month later glomeruli of diabetic rats showed hyaline nodular deposits, exsudative lesions and glomerular aneurysms. The thickening of the mesangium measured by point counting method was statistically significant compared with age matched controls. Large quantities of IgG, beta 1c and fibrinogen in a predominantly mesangial pattern could be demonstrated by fluorescence microscopy. After injection of aggregated immunoglobulin the uptake of IgG by the mesangial cells was delayed in the diabetics compared with normal controls. Islet transplantation resulted in a marked reduction of the light microscopic and immunohistological glomerular lesions and restored the phagocytic capacity of the mesangial cells almost completely. From these results it is concluded, that the fundamental defect in diabetic glomerulosclerosis is a metabolically induced functional defect of the mesangial cells."} {"id": "PMID:155639", "title": "[Menarche in healthy and sick girls with special reference to mongolism].", "content": "The age of menarche in various groups of females was studied. In healthy girls, the average age of menarche was 12 years 2 months regardless of their birthweights. Twin girls had a significantly retarded menarche (approx. 12 years 8 months). In a group of 102 blind patients, it was not significantly different from healthy controls. In a series of 42 girls with mongolism, the mean age of menarche was significantly retarded (13 years 3 months).", "contents": "[Menarche in healthy and sick girls with special reference to mongolism]. The age of menarche in various groups of females was studied. In healthy girls, the average age of menarche was 12 years 2 months regardless of their birthweights. Twin girls had a significantly retarded menarche (approx. 12 years 8 months). In a group of 102 blind patients, it was not significantly different from healthy controls. In a series of 42 girls with mongolism, the mean age of menarche was significantly retarded (13 years 3 months)."} {"id": "PMID:155640", "title": "Further studies on the relationship of adrenal and gonadal steroids in pubertal development in female rats.", "content": "Surgical adrenalectomy or the administration of aminoglutethimide, corticosterone (B), and androstenedione (delta 4) to the immature female rat had no effect on the timing of vaginal membrane opening. Dehydroepiandrosterone (DHA) and estrone (E1) significantly hastened vaginal patency. Aminoglutethimide increased pituitary LH content while FSH content was decreased. An anti-17 beta-E2 antibody increased pituitary LH content and plasma concentration suggesting enhanced synthesis and release of LH. Pituitary FSH content was unaltered while plasma FSH decreased. Aminoglutethimide increased adrenal and ovarian but not pituitary weight while the antibody had no effect. Since little DHA is present in rat plasma and adrenal and since only estrogens have any effect on the onset of puberty, it is likely that the adrenal is not directly involved in pubertal development in the female rat.", "contents": "Further studies on the relationship of adrenal and gonadal steroids in pubertal development in female rats. Surgical adrenalectomy or the administration of aminoglutethimide, corticosterone (B), and androstenedione (delta 4) to the immature female rat had no effect on the timing of vaginal membrane opening. Dehydroepiandrosterone (DHA) and estrone (E1) significantly hastened vaginal patency. Aminoglutethimide increased pituitary LH content while FSH content was decreased. An anti-17 beta-E2 antibody increased pituitary LH content and plasma concentration suggesting enhanced synthesis and release of LH. Pituitary FSH content was unaltered while plasma FSH decreased. Aminoglutethimide increased adrenal and ovarian but not pituitary weight while the antibody had no effect. Since little DHA is present in rat plasma and adrenal and since only estrogens have any effect on the onset of puberty, it is likely that the adrenal is not directly involved in pubertal development in the female rat."} {"id": "PMID:155641", "title": "Kartagener's syndrome and the syndrome of immotile cilia.", "content": "Kartagener's syndrome (KS) is a hereditary disease with typical symptoms of situs inversus, bronchiectasis, and chronic infections of the nasal mucosa. Autosomal recessive inheritance cannot be doubted on account of repeated observations of affected sibs and parental cansanguinity. The bronchopulmonary symptoms in sibs, however, cannot be explained by this mode of inheritance. Recent clinical findings and electron microscope investigations suggest that KS is a special form of manifestation within the immotile cilia syndrome. This disease combines the typical bronchial and nasal symptoms of KS with sterility in the male due to immotile sperm tails and, as a facultative symptom, situs inversus. Thus, sibs with bronchiectasis but without situs inversus are also classified under this syndrome. The symptoms mentioned are caused by an abnormal morphology of bronchial cilia and sperm tails, which can be demonstrated by electron microscopy. The dynein arms normally attached to the nine microtubular doublets and providing a normal ciliary movement are lacking. It is assumed that during early embryonic life ciliary beats in the growing embryo determine the type of laterality. When ciliary movements are absent laterality may develop fortuitously, thus effecting a situs inversus in about half the affected cases. The numerical evaluation of pedigrees from the literature supports this assumption.", "contents": "Kartagener's syndrome and the syndrome of immotile cilia. Kartagener's syndrome (KS) is a hereditary disease with typical symptoms of situs inversus, bronchiectasis, and chronic infections of the nasal mucosa. Autosomal recessive inheritance cannot be doubted on account of repeated observations of affected sibs and parental cansanguinity. The bronchopulmonary symptoms in sibs, however, cannot be explained by this mode of inheritance. Recent clinical findings and electron microscope investigations suggest that KS is a special form of manifestation within the immotile cilia syndrome. This disease combines the typical bronchial and nasal symptoms of KS with sterility in the male due to immotile sperm tails and, as a facultative symptom, situs inversus. Thus, sibs with bronchiectasis but without situs inversus are also classified under this syndrome. The symptoms mentioned are caused by an abnormal morphology of bronchial cilia and sperm tails, which can be demonstrated by electron microscopy. The dynein arms normally attached to the nine microtubular doublets and providing a normal ciliary movement are lacking. It is assumed that during early embryonic life ciliary beats in the growing embryo determine the type of laterality. When ciliary movements are absent laterality may develop fortuitously, thus effecting a situs inversus in about half the affected cases. The numerical evaluation of pedigrees from the literature supports this assumption."} {"id": "PMID:155642", "title": "Origin of trisomies in human spontaneous abortions.", "content": "Chromosome heteromorphisms of 34 trisomic abortuses and their parents were compared to determine the origin of the extra chromosome. Fourteen of the trisomies were maternal in origin, ten resulting from a first-meiotic-division error and four from either first- or second-meiotic-division errors. No paternally derived trisomy was identified.", "contents": "Origin of trisomies in human spontaneous abortions. Chromosome heteromorphisms of 34 trisomic abortuses and their parents were compared to determine the origin of the extra chromosome. Fourteen of the trisomies were maternal in origin, ten resulting from a first-meiotic-division error and four from either first- or second-meiotic-division errors. No paternally derived trisomy was identified."} {"id": "PMID:155643", "title": "Pericentric inversions of chromosome number 9: benign or harmful?", "content": "Pericentric inversions of chromosome number 9 have been studied in 4 different probands: a normal female with designation 46,XX,inv(9)(p12q13); a male with Down syndrome designated as 47,XY,+21,inv(9))p13q13); a premature infant with multiple, congenital malformations who was 46,XX,inv(9)(p12q21), and a Down syndrome proband with 47,XYqs,+21,inv(9)(p13q21). All 4 cases were shown to be inherited based on family studies. These families are discussed with reference to the literature as to what possible effect this structural change could have on the reproductive capability of a normal carrier and what guidelines are available for counseling such a carrier.", "contents": "Pericentric inversions of chromosome number 9: benign or harmful? Pericentric inversions of chromosome number 9 have been studied in 4 different probands: a normal female with designation 46,XX,inv(9)(p12q13); a male with Down syndrome designated as 47,XY,+21,inv(9))p13q13); a premature infant with multiple, congenital malformations who was 46,XX,inv(9)(p12q21), and a Down syndrome proband with 47,XYqs,+21,inv(9)(p13q21). All 4 cases were shown to be inherited based on family studies. These families are discussed with reference to the literature as to what possible effect this structural change could have on the reproductive capability of a normal carrier and what guidelines are available for counseling such a carrier."} {"id": "PMID:155644", "title": "A new N-acetyl-beta-D-hexosaminidase disease with late onset of progressive neurological symptoms.", "content": "Clinical data are presented on a 30-year-old male with normal early development (4-5 years) but subsequent progressive impairment of psychomotor functions. He has marked kyphoscoliosis and talipes calcaneo-valgus. The organs appear normal and the patient can walk unaided and feed himself although he does not recognize his parents. He has normal fundi oculi. Biochemical data show an absence of mucopolysacchariduria and very low but detectable levels of N-acetyl-beta-D-hexosaminidase in serum and leucocytes. The clinical symptoms are much milder than would normally be expected from such a profound enzyme deficiency (Sandhoff disease).", "contents": "A new N-acetyl-beta-D-hexosaminidase disease with late onset of progressive neurological symptoms. Clinical data are presented on a 30-year-old male with normal early development (4-5 years) but subsequent progressive impairment of psychomotor functions. He has marked kyphoscoliosis and talipes calcaneo-valgus. The organs appear normal and the patient can walk unaided and feed himself although he does not recognize his parents. He has normal fundi oculi. Biochemical data show an absence of mucopolysacchariduria and very low but detectable levels of N-acetyl-beta-D-hexosaminidase in serum and leucocytes. The clinical symptoms are much milder than would normally be expected from such a profound enzyme deficiency (Sandhoff disease)."} {"id": "PMID:155645", "title": "The role of monocytes in phagocytosis and mixed leukocyte reactivity in human acute myeloid leukemia.", "content": "Lymphocyte proliferation, as measured by incorporation of tritiated thymidine (3H-TdR), was significantly enhanced (p less than 0.01) when macrophages sensitized by target myeloblasts were added to monocyte-depleted lymphocyte fractions in the mixed leukocyte reaction (MLR) with human leukemic myeloblasts as stimulators and panels of normal lymphocytes as responders. Monocyte addition in the same concentration range to unfractionated lymphocytes resulted in highly significant facilitation (p less than 0.0001) of MLR response patterns to myeloblastic stimulation. However, with substitution of a different myeloblastic stimulator, this facilitation was not observed. At higher monocyte-lymphocyte ratios (1:15) the monocytes appeared to be capable of strongly inhibiting the MLR. Monocyte capacity to engulf and kill Candida albicans organisms was normal in acute myeloid leukemia (AML) patients given \"immunotherapy\" with BCG and leukemic cells.", "contents": "The role of monocytes in phagocytosis and mixed leukocyte reactivity in human acute myeloid leukemia. Lymphocyte proliferation, as measured by incorporation of tritiated thymidine (3H-TdR), was significantly enhanced (p less than 0.01) when macrophages sensitized by target myeloblasts were added to monocyte-depleted lymphocyte fractions in the mixed leukocyte reaction (MLR) with human leukemic myeloblasts as stimulators and panels of normal lymphocytes as responders. Monocyte addition in the same concentration range to unfractionated lymphocytes resulted in highly significant facilitation (p less than 0.0001) of MLR response patterns to myeloblastic stimulation. However, with substitution of a different myeloblastic stimulator, this facilitation was not observed. At higher monocyte-lymphocyte ratios (1:15) the monocytes appeared to be capable of strongly inhibiting the MLR. Monocyte capacity to engulf and kill Candida albicans organisms was normal in acute myeloid leukemia (AML) patients given \"immunotherapy\" with BCG and leukemic cells."} {"id": "PMID:155646", "title": "Stimulating capacity of blast cells from patients with chronic myelocytic leukaemia, in blastic crisis in 'one-way' mixed lymphoycte reaction: lack of evidence for T lymphoblastic conversion.", "content": "It has long been suggested that the blastic transformation in some patients with Ph1-positive chronic myelocytic leukaemia (CML) may be lymphoid in nature. It has recently been postulated that some patients with CML may undergo a T lymphoblastic crisis because the leukaemic blasts from these patients have high terminal deoxynucleotidyl transferase (TdT) activity and that some patients may undergo a non-T/non-B lymphoblastic crisis since leukaemic blasts from a majority of morphologically lymphoid type CML-BC cases react with antiserum specific for non-T/non-B acute lymphoblastic leukaemia (ALL). The present study shows that leukaemic blasts from each of six patients with Ph1-positive chronic myelocytic leukaemia-blastic crisis (CML-BC) exerted a strong stimulation on allogeneic lymphocytes in 'one-way' mixed lymphocyte reaction. There was no apparent difference in stimulating capacity between morphologically myeloid type (four cases) and lymphoid type (two cases). The stimulating capacity of leukaemic blasts from patients with CML-BC was quite similar to that of blasts from all patients with acute myeloblastic leukaemia (AML) and from some patients with non-T/non-B type ALL. Leukaemic blasts from a patient with T-cell type ALL and cultured leukaemic T lymphoblastoid cells (2 lines) consistently failed to stimulate while cultured leukaemic null-cells (4 lines) consistently exerted a strong stimulation in 'one-way' mixed lymphocyte reaction. These observations suggest that leukaemic cells from patients with CML-BC, morphologically lymphoblastic type, are not T lymphoblasts although the possibility that these cells are non-T/non-B lymphoblasts cannot be ruled out entirely.", "contents": "Stimulating capacity of blast cells from patients with chronic myelocytic leukaemia, in blastic crisis in 'one-way' mixed lymphoycte reaction: lack of evidence for T lymphoblastic conversion. It has long been suggested that the blastic transformation in some patients with Ph1-positive chronic myelocytic leukaemia (CML) may be lymphoid in nature. It has recently been postulated that some patients with CML may undergo a T lymphoblastic crisis because the leukaemic blasts from these patients have high terminal deoxynucleotidyl transferase (TdT) activity and that some patients may undergo a non-T/non-B lymphoblastic crisis since leukaemic blasts from a majority of morphologically lymphoid type CML-BC cases react with antiserum specific for non-T/non-B acute lymphoblastic leukaemia (ALL). The present study shows that leukaemic blasts from each of six patients with Ph1-positive chronic myelocytic leukaemia-blastic crisis (CML-BC) exerted a strong stimulation on allogeneic lymphocytes in 'one-way' mixed lymphocyte reaction. There was no apparent difference in stimulating capacity between morphologically myeloid type (four cases) and lymphoid type (two cases). The stimulating capacity of leukaemic blasts from patients with CML-BC was quite similar to that of blasts from all patients with acute myeloblastic leukaemia (AML) and from some patients with non-T/non-B type ALL. Leukaemic blasts from a patient with T-cell type ALL and cultured leukaemic T lymphoblastoid cells (2 lines) consistently failed to stimulate while cultured leukaemic null-cells (4 lines) consistently exerted a strong stimulation in 'one-way' mixed lymphocyte reaction. These observations suggest that leukaemic cells from patients with CML-BC, morphologically lymphoblastic type, are not T lymphoblasts although the possibility that these cells are non-T/non-B lymphoblasts cannot be ruled out entirely."} {"id": "PMID:155647", "title": "Use of stimulating capacity of mixed lymphocyte reaction (MLR-S) as a possible marker for the cell-origin of null-cell acute lymphoblastic leukaemia.", "content": "The recent introduction of surface marker analysis indicates that the T-cell ALL represents 15--25%, the B-cell ALL represents less than 5% and the null-cell ALL represents more than 70% of cases. The origin of leukaemic null-cells is at present not clear. The present study shows that fresh leukaemic cells from five patients with null-cell ALL exerted a strong stimulating effect while the leukaemic cells from three patients with null-cell ALL failed to stimulate in 'one-way' MLR. Cultured leukaemic cells from three null-cell lines (NALM-16, NALL-1 and MOLT-10) consistently exerted a strong stimulation while leukaemic cells from one null-cell line (REH) exerted little or no stimulation on allogeneic lymphocytes. Leukaemic null-cells from the NALM-,6 line exhibited a lesser but significant stimulation in 'one-way' MLR. These observations lead us to speculate that leukaemic null-cells which possess a stimulating capacity may represent less differentiated leukaemic B lymphoid cells (early B-cell precursors) and leukaemic null-cells which possess no stimulating capacity may represent less differentiated leukaemic T lymphoid cells (early T-cell precursor).", "contents": "Use of stimulating capacity of mixed lymphocyte reaction (MLR-S) as a possible marker for the cell-origin of null-cell acute lymphoblastic leukaemia. The recent introduction of surface marker analysis indicates that the T-cell ALL represents 15--25%, the B-cell ALL represents less than 5% and the null-cell ALL represents more than 70% of cases. The origin of leukaemic null-cells is at present not clear. The present study shows that fresh leukaemic cells from five patients with null-cell ALL exerted a strong stimulating effect while the leukaemic cells from three patients with null-cell ALL failed to stimulate in 'one-way' MLR. Cultured leukaemic cells from three null-cell lines (NALM-16, NALL-1 and MOLT-10) consistently exerted a strong stimulation while leukaemic cells from one null-cell line (REH) exerted little or no stimulation on allogeneic lymphocytes. Leukaemic null-cells from the NALM-,6 line exhibited a lesser but significant stimulation in 'one-way' MLR. These observations lead us to speculate that leukaemic null-cells which possess a stimulating capacity may represent less differentiated leukaemic B lymphoid cells (early B-cell precursors) and leukaemic null-cells which possess no stimulating capacity may represent less differentiated leukaemic T lymphoid cells (early T-cell precursor)."} {"id": "PMID:155648", "title": "Rhodamine as a fluorescent probe of lymphocyte activation.", "content": "Fresh rat and mouse lymphoid cells have been labelled by stable linkage with tetramethylrhodamine isothiocyanate (TMRITC). A change in intensity, either an increase or decrease of the fluorescent emission of the cells, detected by microfluorimetry, was induced by mitogen stimulation or the mixed lymphocyte reaction. The change in fluorescence was observed within 3 h of mitogen stimulation and within 0.5 h in the mixed lymphocyte test. These early cellular responses were detectable consistently whether the labelling was done before or after mitogen stimulation; post-labelling only was studied in the mixed lymphocyte reaction. The method should provide a time-saving practical procedure for early detection of the lymphoid cell responses and would readily lend itself to flow cytofluorimetry for possible routine diagnostic use.", "contents": "Rhodamine as a fluorescent probe of lymphocyte activation. Fresh rat and mouse lymphoid cells have been labelled by stable linkage with tetramethylrhodamine isothiocyanate (TMRITC). A change in intensity, either an increase or decrease of the fluorescent emission of the cells, detected by microfluorimetry, was induced by mitogen stimulation or the mixed lymphocyte reaction. The change in fluorescence was observed within 3 h of mitogen stimulation and within 0.5 h in the mixed lymphocyte test. These early cellular responses were detectable consistently whether the labelling was done before or after mitogen stimulation; post-labelling only was studied in the mixed lymphocyte reaction. The method should provide a time-saving practical procedure for early detection of the lymphoid cell responses and would readily lend itself to flow cytofluorimetry for possible routine diagnostic use."} {"id": "PMID:155649", "title": "Enhanced release of lipase from stimulated mouse spleen cells.", "content": "We detected lipase activity in an homogenate of mouse spleen- and lymph node cells by using [3H]-triolein as a lipase substrate. Lipase activity was also detected in an homogenate of human peripheral blood lymphocytes. Furthermore, in mouse spleen cell culture medium we observed increased lipase activity following stimulation of mouse spleen cells with phytohaemagglutinin (PHA) as well as allogeneic spleen cells. Therefore, we suggest that lipase may be a kind of lymphokine.", "contents": "Enhanced release of lipase from stimulated mouse spleen cells. We detected lipase activity in an homogenate of mouse spleen- and lymph node cells by using [3H]-triolein as a lipase substrate. Lipase activity was also detected in an homogenate of human peripheral blood lymphocytes. Furthermore, in mouse spleen cell culture medium we observed increased lipase activity following stimulation of mouse spleen cells with phytohaemagglutinin (PHA) as well as allogeneic spleen cells. Therefore, we suggest that lipase may be a kind of lymphokine."} {"id": "PMID:155650", "title": "Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis.", "content": "T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential.", "contents": "Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis. T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential."} {"id": "PMID:155651", "title": "Human-mouse mixed lymphocyte cultures. II. Partial separation of functionally distinct populations on discontinuous albumin gradients.", "content": "Human-mouse mixed lymphocyte cultures (MLC) develop stable, strain-specific responses directed towards antigens determined by the mouse major histocompatibility complex (MHC). By restimulation in vitro a two- to four-fold increase in total cell numbers can be achieved. Sensitized cells can be fractionated on discontinuous BSA gradients to produce fractions with predominantly proliferative or cytotoxic activity towards the intiating antigens. Mixing experiments show that fractionation of biological activity is the result of fractination of specifically sensitized effector cells rather than fractionation of inhibitory or collaborative elements. Since biological activities or can be separated on the basis of physical properties into distinct cell populations these experiments support the idea that these functions are the properties of distinct subclasses of human T lymphocyte. Xenogeneic MLC coupled to physical separation measures is a useful approach to the study of antigen-specific human T lymphocytes.", "contents": "Human-mouse mixed lymphocyte cultures. II. Partial separation of functionally distinct populations on discontinuous albumin gradients. Human-mouse mixed lymphocyte cultures (MLC) develop stable, strain-specific responses directed towards antigens determined by the mouse major histocompatibility complex (MHC). By restimulation in vitro a two- to four-fold increase in total cell numbers can be achieved. Sensitized cells can be fractionated on discontinuous BSA gradients to produce fractions with predominantly proliferative or cytotoxic activity towards the intiating antigens. Mixing experiments show that fractionation of biological activity is the result of fractination of specifically sensitized effector cells rather than fractionation of inhibitory or collaborative elements. Since biological activities or can be separated on the basis of physical properties into distinct cell populations these experiments support the idea that these functions are the properties of distinct subclasses of human T lymphocyte. Xenogeneic MLC coupled to physical separation measures is a useful approach to the study of antigen-specific human T lymphocytes."} {"id": "PMID:155652", "title": "The blastogenic response of rabbit lymphocytes stimulated with autologous cells.", "content": "Rabbit WBC and spleen cells respond with marked blastogenesis and mitosis when cultured with mitomycin-C treated autologous sacculus rotundus, appendix and Peyer's patches cells in the one-way rabbit mixed leucocyte reaction (MLR). A lesser response is observed using stimulating cells of the other lymphoid organs. The blastogenic response in the one-way 'autologous MLR' cannot be attributed to mitogenic factors released from the mitomycin-C treated stimulator cells since it is also observed in the 'two-way autologous MLR', using untreated stimulator cells. Several explanations are proposed to account for the 'autologous MLR'.", "contents": "The blastogenic response of rabbit lymphocytes stimulated with autologous cells. Rabbit WBC and spleen cells respond with marked blastogenesis and mitosis when cultured with mitomycin-C treated autologous sacculus rotundus, appendix and Peyer's patches cells in the one-way rabbit mixed leucocyte reaction (MLR). A lesser response is observed using stimulating cells of the other lymphoid organs. The blastogenic response in the one-way 'autologous MLR' cannot be attributed to mitogenic factors released from the mitomycin-C treated stimulator cells since it is also observed in the 'two-way autologous MLR', using untreated stimulator cells. Several explanations are proposed to account for the 'autologous MLR'."} {"id": "PMID:155653", "title": "Virus plaque assay: effective detection of virus plaque forming cells at the early stage of lymphocyte activation by mitogen and alloantigen.", "content": "Activated lymphocytes were detected quantitatively by virus plaque assay (VPA) during the course of lymphocyte cultures stimulated by mitogen or alloantigen. In Con A-stimulated cultures, the number of virus-plaque forming cells (V--PFC) was a more sensitive method of detecting the early stage of lymphocyte activation than [3H]-thymidine (3H-TdR) incorporation. This evidence was obtained by two methods of collecting cells of each stage. First, when Con A-activated lymphocytes were fractionated by velocity sedimentation at unit gravity to separate cell populations according to each cell stage, the ratio of the number of V-PFC to the radioactivity of incorporated [3H]-TdR was larger in the earlier stage of cell cycle than in the later stage. Second, when cultured lymphocytes were synchronized directly by addition of excess thymidine and colchicine, similar results were obtained. In primary mixed lymphocyte cultures, the generation of cytotoxic lymphocytes (CTL) was correlated better with the proliferative response than with V-PFC production. It was also found that both the incorporation of [3H]-TdR and the generation of CTL were abrogated by cytosine arabinoside (Ara-C) added to cultures up to one day before assay, whilst the generation of V-PFC was not so markedly affected by Ara-C. These findings suggest that V-PFC represent the number of precursor cells which require one or more generations to differentiate to CTL and not simply the number of effector lymphoyctes already exhibiting cytotoxicity.", "contents": "Virus plaque assay: effective detection of virus plaque forming cells at the early stage of lymphocyte activation by mitogen and alloantigen. Activated lymphocytes were detected quantitatively by virus plaque assay (VPA) during the course of lymphocyte cultures stimulated by mitogen or alloantigen. In Con A-stimulated cultures, the number of virus-plaque forming cells (V--PFC) was a more sensitive method of detecting the early stage of lymphocyte activation than [3H]-thymidine (3H-TdR) incorporation. This evidence was obtained by two methods of collecting cells of each stage. First, when Con A-activated lymphocytes were fractionated by velocity sedimentation at unit gravity to separate cell populations according to each cell stage, the ratio of the number of V-PFC to the radioactivity of incorporated [3H]-TdR was larger in the earlier stage of cell cycle than in the later stage. Second, when cultured lymphocytes were synchronized directly by addition of excess thymidine and colchicine, similar results were obtained. In primary mixed lymphocyte cultures, the generation of cytotoxic lymphocytes (CTL) was correlated better with the proliferative response than with V-PFC production. It was also found that both the incorporation of [3H]-TdR and the generation of CTL were abrogated by cytosine arabinoside (Ara-C) added to cultures up to one day before assay, whilst the generation of V-PFC was not so markedly affected by Ara-C. These findings suggest that V-PFC represent the number of precursor cells which require one or more generations to differentiate to CTL and not simply the number of effector lymphoyctes already exhibiting cytotoxicity."} {"id": "PMID:155654", "title": "Allograft cytotoxicity: differences between lytic and non-lytic interactions as revealed by ultrastructural histochemistry.", "content": "Alloimmune and normal mouse (C57Bl/10) spleen cells and tumour cells (P815Y) were cultured together in flat-bottomed microtitre plates. Cytolytic activity was assessed by the 51Cr release assay in combination with histological analyses. Cells were fixed and embedded in situ and substrates to reveal ATPase or, alternatively, endogenous peroxidase activities, were applied. Both lymphocytes and monocytes formed junctions with the target cells and estimates of their relative frequencies were produced. Junctions between lymphocytes and tumour cells were completely ablated by treatment with anti-brain-associated theta and complement. Junctions involving immune lymphocytes were typically associated with locally increased ATPase activity in the target cell membrane. Neither monocytes nor normal lymphocytes increased local ATPase activity or 51Cr release to any significant extent.", "contents": "Allograft cytotoxicity: differences between lytic and non-lytic interactions as revealed by ultrastructural histochemistry. Alloimmune and normal mouse (C57Bl/10) spleen cells and tumour cells (P815Y) were cultured together in flat-bottomed microtitre plates. Cytolytic activity was assessed by the 51Cr release assay in combination with histological analyses. Cells were fixed and embedded in situ and substrates to reveal ATPase or, alternatively, endogenous peroxidase activities, were applied. Both lymphocytes and monocytes formed junctions with the target cells and estimates of their relative frequencies were produced. Junctions between lymphocytes and tumour cells were completely ablated by treatment with anti-brain-associated theta and complement. Junctions involving immune lymphocytes were typically associated with locally increased ATPase activity in the target cell membrane. Neither monocytes nor normal lymphocytes increased local ATPase activity or 51Cr release to any significant extent."} {"id": "PMID:155659", "title": "Inhibition of mixed-lymphocyte reaction by quinine and lack of effect on plaque-forming cells and lymphoid-derived tumor cells.", "content": "Using Balb/c cells as responder cells and mitomycin-treated C57B1 cells as stimulator cells, it was found that quinine was inhibitory in a one-way mixed-lymphocyte reaction. Incorporation of [3H]-TdR was brought down to base levels in the presence of quinine. Quinine was not toxic for antibody-forming cells, and had no effect on plaque-forming cells formed by antibody-committed cells. The degree of [3H]-TdR incorporation of MOPC-315 tumor cells and Burkitt's lymphoma cells was not affected by the presence of quinine in the medium. The cytotoxicity of quinine for mitogen-stimulated cells was demonstrated in soft-agar cultures.", "contents": "Inhibition of mixed-lymphocyte reaction by quinine and lack of effect on plaque-forming cells and lymphoid-derived tumor cells. Using Balb/c cells as responder cells and mitomycin-treated C57B1 cells as stimulator cells, it was found that quinine was inhibitory in a one-way mixed-lymphocyte reaction. Incorporation of [3H]-TdR was brought down to base levels in the presence of quinine. Quinine was not toxic for antibody-forming cells, and had no effect on plaque-forming cells formed by antibody-committed cells. The degree of [3H]-TdR incorporation of MOPC-315 tumor cells and Burkitt's lymphoma cells was not affected by the presence of quinine in the medium. The cytotoxicity of quinine for mitogen-stimulated cells was demonstrated in soft-agar cultures."} {"id": "PMID:155661", "title": "Measuring attitudes toward the physically disabled: testing the 'Attitude Towards Disabled Persons' scale (A.T.D.P. Form O) on social work and non-social work students.", "content": "The aim of the study was to test the U.S.A. Validated 'Attitude Towards Disabled Persons' Inventory (A.T.D.P. Form O) on a British student population to establish norms. The objectives were to test specific hypotheses related to the sex of the respondent, contact with physically disabled people and whether social work students had different attitude scores than non social work students. In addition, a comparison was made between the British and U.S.A. 'norms'. The student population of four specific British Universities comprised the sampling frame. The sample was a non probability accidental sample of social work and non social work students. Standardised A.T.D.P. Form Os were administered in group situations. Each form was accompanied by a letter explaining the study, together with a short questionnaire eliciting the sex of respondent and type and extent of any contact with disabled people. The findings demonstrated that there are probably differences between U.S.A. and British norms but that there are general similarities between the two countries. In both countries females, scored higher than males, which by interpretation indicates possibly a more favourable attitude. Contact with the disabled is also a contributing factor in higher scores. Social work students also tended to score more highly than non social work students. The implications of these findings are discussed with regard to the possible development of professional attitudes for those who work with the disabled. It is postulated that 'idealisation' may be reflected in attitudes of students who intend to work with the disabled which, after general and professional life experience gives way to less favourable attitudes. Closeness of contact of respondents to disabled people is a factor which needs further exploration in connection with changing attitude scores.", "contents": "Measuring attitudes toward the physically disabled: testing the 'Attitude Towards Disabled Persons' scale (A.T.D.P. Form O) on social work and non-social work students. The aim of the study was to test the U.S.A. Validated 'Attitude Towards Disabled Persons' Inventory (A.T.D.P. Form O) on a British student population to establish norms. The objectives were to test specific hypotheses related to the sex of the respondent, contact with physically disabled people and whether social work students had different attitude scores than non social work students. In addition, a comparison was made between the British and U.S.A. 'norms'. The student population of four specific British Universities comprised the sampling frame. The sample was a non probability accidental sample of social work and non social work students. Standardised A.T.D.P. Form Os were administered in group situations. Each form was accompanied by a letter explaining the study, together with a short questionnaire eliciting the sex of respondent and type and extent of any contact with disabled people. The findings demonstrated that there are probably differences between U.S.A. and British norms but that there are general similarities between the two countries. In both countries females, scored higher than males, which by interpretation indicates possibly a more favourable attitude. Contact with the disabled is also a contributing factor in higher scores. Social work students also tended to score more highly than non social work students. The implications of these findings are discussed with regard to the possible development of professional attitudes for those who work with the disabled. It is postulated that 'idealisation' may be reflected in attitudes of students who intend to work with the disabled which, after general and professional life experience gives way to less favourable attitudes. Closeness of contact of respondents to disabled people is a factor which needs further exploration in connection with changing attitude scores."} {"id": "PMID:155665", "title": "[Paraneoplastic acrokeratosis].", "content": "Paraneoplastic acrokeratosis is a distinctive dermatosis observed only in patients with either carcinoma of the upper respiratory and digestive tract or with metastatic lymphnodes in the cervical or mediastinal region. The characteristics of this dermatosis are: acral beginning, erythematous, squamous and hyperkeratotic plaques with centripedal spreading and healing only after successful treatment of the carcinoma. An allergic or toxic skin reaction to a substance formed by the tumor cells is discussed as causative agent. The author gives a review of the symptoms, the course of the disease, of histological and biochemical data and of the differential diagnosis as reported in the literature.", "contents": "[Paraneoplastic acrokeratosis]. Paraneoplastic acrokeratosis is a distinctive dermatosis observed only in patients with either carcinoma of the upper respiratory and digestive tract or with metastatic lymphnodes in the cervical or mediastinal region. The characteristics of this dermatosis are: acral beginning, erythematous, squamous and hyperkeratotic plaques with centripedal spreading and healing only after successful treatment of the carcinoma. An allergic or toxic skin reaction to a substance formed by the tumor cells is discussed as causative agent. The author gives a review of the symptoms, the course of the disease, of histological and biochemical data and of the differential diagnosis as reported in the literature."} {"id": "PMID:155666", "title": "[Trichophyton mentagrophytes var. erinacei infection contracted from a hedgehog].", "content": "Occasionally the hedgehog (Erinaceus europaeus) is infected by Trichophyton mentagrophytes (Robin) Blanchard var. erinacei. This zoophilic dermatophyte may cause a difficult human phlegmatic trichophytia infection. The thread-fungus grows on the usual culture-medium with a clear-white surface without radius-folding. The lower surface of the culture shows a typical brillant-yellow colour. Microscopically the fungus presents abundant microconidia formation and a few distinct macroconidia. Cross-breeding with the tester strain Arthroderma simii \"+\" was negative, with \"-\" showed an increased growth and a formation of cleistothecium-primordia in the combination zone.", "contents": "[Trichophyton mentagrophytes var. erinacei infection contracted from a hedgehog]. Occasionally the hedgehog (Erinaceus europaeus) is infected by Trichophyton mentagrophytes (Robin) Blanchard var. erinacei. This zoophilic dermatophyte may cause a difficult human phlegmatic trichophytia infection. The thread-fungus grows on the usual culture-medium with a clear-white surface without radius-folding. The lower surface of the culture shows a typical brillant-yellow colour. Microscopically the fungus presents abundant microconidia formation and a few distinct macroconidia. Cross-breeding with the tester strain Arthroderma simii \"+\" was negative, with \"-\" showed an increased growth and a formation of cleistothecium-primordia in the combination zone."} {"id": "PMID:155668", "title": "The structure of the Harderian and lacrimal gland ducts of the turkey, fowl and duck. A light microscope study.", "content": "The secretory ducts of the Harderian and lacrimal glands of the turkey, fowl and duck are similar in both structure and function. The single duct of each gland is lined by mucus-secreting epithelium. The epithelial cells vary from cuboidal to columnar, and goblet cells of three types are found. Type A, the most numerous, contain neutral mucopolysaccharides, type B have mixed acid and sulphated mucosubstances and type C, the least numerous, contain acid mucins. In both ducts glycogen is present in the lumen, but it occurs intracellularly only in the fowl up to seven days after hatching. Lymphocytes, either as diffuse tissue or as germinal centres, are found scattered along the length of the ducts. Some plasma cells and plasmablasts are also present.", "contents": "The structure of the Harderian and lacrimal gland ducts of the turkey, fowl and duck. A light microscope study. The secretory ducts of the Harderian and lacrimal glands of the turkey, fowl and duck are similar in both structure and function. The single duct of each gland is lined by mucus-secreting epithelium. The epithelial cells vary from cuboidal to columnar, and goblet cells of three types are found. Type A, the most numerous, contain neutral mucopolysaccharides, type B have mixed acid and sulphated mucosubstances and type C, the least numerous, contain acid mucins. In both ducts glycogen is present in the lumen, but it occurs intracellularly only in the fowl up to seven days after hatching. Lymphocytes, either as diffuse tissue or as germinal centres, are found scattered along the length of the ducts. Some plasma cells and plasmablasts are also present."} {"id": "PMID:155669", "title": "Interaction of aminoglycosides and other antibiotics with actin.", "content": "Skeletal muscle actin was found by centrifugation, turbidity, and viscosity measurements to form polymers upon addition of aminoglycosides, viomycin, polymyxin B, and tetracycline. A linear relationship was observed between the amount of actin polymerization and the number of primary amino groups on the aminoglycoside antibiotics except kanamycin. Of the antibiotics studied, neomycin was most efficient in actin polymerization. Polymerization of actin was not significantly induced by kasugamycin, chloramphenicol, erythromycin, benzylpenicillin, angustmycin A, formycin, actinomycin D, and mitomycin C. Aminoglycosides and viomycin were demonstrated to inhibit the acto-HMM Mg(2+)-ATPase reaction but did not significantly affect HMM Mg(2+)-ATPase activity. It was found by equilibrium dialysis that [(3)H]dihydrostreptomycin bound to actin.", "contents": "Interaction of aminoglycosides and other antibiotics with actin. Skeletal muscle actin was found by centrifugation, turbidity, and viscosity measurements to form polymers upon addition of aminoglycosides, viomycin, polymyxin B, and tetracycline. A linear relationship was observed between the amount of actin polymerization and the number of primary amino groups on the aminoglycoside antibiotics except kanamycin. Of the antibiotics studied, neomycin was most efficient in actin polymerization. Polymerization of actin was not significantly induced by kasugamycin, chloramphenicol, erythromycin, benzylpenicillin, angustmycin A, formycin, actinomycin D, and mitomycin C. Aminoglycosides and viomycin were demonstrated to inhibit the acto-HMM Mg(2+)-ATPase reaction but did not significantly affect HMM Mg(2+)-ATPase activity. It was found by equilibrium dialysis that [(3)H]dihydrostreptomycin bound to actin."} {"id": "PMID:155664", "title": "Radiofrequency facet rhizotomy in the treatment of chronic neck and low back pain.", "content": "The value of radiofrequency facet rhizotomy in the treatment of patients with chronic neck and low back pain problems is assessed on the basis of experience with 117 consecutive patients. Only patients with positive responses to facet blocking with local anesthetic were selected. Overall results in 50 neck procedures were: excellent, 16%; good, 34%; fair, 18%; poor, 28%; and lost to follow-up, 4%. In the 71 lumbar rhizotomies results were: excellent, 15%; good, 20%; fair, 27%; poor, 31%; and lost to follow-up, 7%. Average follow-up time was 13.7 months. We conclude that radiofrequency rhizotomy is a valuable tool in the treatment of chronic neck and low back pain.", "contents": "Radiofrequency facet rhizotomy in the treatment of chronic neck and low back pain. The value of radiofrequency facet rhizotomy in the treatment of patients with chronic neck and low back pain problems is assessed on the basis of experience with 117 consecutive patients. Only patients with positive responses to facet blocking with local anesthetic were selected. Overall results in 50 neck procedures were: excellent, 16%; good, 34%; fair, 18%; poor, 28%; and lost to follow-up, 4%. In the 71 lumbar rhizotomies results were: excellent, 15%; good, 20%; fair, 27%; poor, 31%; and lost to follow-up, 7%. Average follow-up time was 13.7 months. We conclude that radiofrequency rhizotomy is a valuable tool in the treatment of chronic neck and low back pain."} {"id": "PMID:155670", "title": "Effect of primycin on the inner membrane permeability of rat liver mitochondria.", "content": "The effects of primycin on mitochondrial respiration, volume changes, ATPase activity and the acidification following ATP hydrolysis were studied. Primycin in concentrations below 2--3 nmoles/mg mitochondrial protein reacts only with energized mitochondria rendering their inner membrane permeable to K+, Na+, Tris+ but not to TEA+. Above this concentration primycin interacts both with energized and deenergized mitochondria and the inner membrane also becomes permeable for H+, Cl- but not for ATP. In this case mitochondria very probably lose Mg2+. It is concluded that primycin up to concentrations of 2--3 nmoles/mg mitochondrial protein acts like an ionophore, while at higher concentrations it changes the permeability properties of the mitochondrial inner membrane without a drastic alteration of the membrane itself.", "contents": "Effect of primycin on the inner membrane permeability of rat liver mitochondria. The effects of primycin on mitochondrial respiration, volume changes, ATPase activity and the acidification following ATP hydrolysis were studied. Primycin in concentrations below 2--3 nmoles/mg mitochondrial protein reacts only with energized mitochondria rendering their inner membrane permeable to K+, Na+, Tris+ but not to TEA+. Above this concentration primycin interacts both with energized and deenergized mitochondria and the inner membrane also becomes permeable for H+, Cl- but not for ATP. In this case mitochondria very probably lose Mg2+. It is concluded that primycin up to concentrations of 2--3 nmoles/mg mitochondrial protein acts like an ionophore, while at higher concentrations it changes the permeability properties of the mitochondrial inner membrane without a drastic alteration of the membrane itself."} {"id": "PMID:155684", "title": "Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification.", "content": "The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A \"socially impaired\" group (more than half of whom were severely retarded) and a comparison group of \"sociable severely mentally retarded\" children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered.", "contents": "Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification. The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A \"socially impaired\" group (more than half of whom were severely retarded) and a comparison group of \"sociable severely mentally retarded\" children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered."} {"id": "PMID:155685", "title": "A case of infantile autism associated with Down's syndrome.", "content": "There is increasing recognition that autism is a syndrome, not a disease entity. But it is not yet clear why some children develop autistic behavior more easily than others. It has been noted that autistic symptoms occur more frequently in children with mental retardation, blindness, congenital rubella, phenylketonuria, etc., and that there are very few cases of classical infantile autism in the general population. Very rarely has autism been associated with Down's syndrome. This is a report of a case of Down's syndrome and infantile autism.", "contents": "A case of infantile autism associated with Down's syndrome. There is increasing recognition that autism is a syndrome, not a disease entity. But it is not yet clear why some children develop autistic behavior more easily than others. It has been noted that autistic symptoms occur more frequently in children with mental retardation, blindness, congenital rubella, phenylketonuria, etc., and that there are very few cases of classical infantile autism in the general population. Very rarely has autism been associated with Down's syndrome. This is a report of a case of Down's syndrome and infantile autism."} {"id": "PMID:155686", "title": "Characterization of the carbohydrate component of fraction I in the Neurospora crassa cell wall.", "content": "The carbohydrate portion of fraction I of the Neurospora crassa cell wall has been analyzed for sugar composition by gas-liquid chromatography and colorimetric methods. The analysis was performed comparatively in a wild-type strain (RL 3-8A) and three morphological mutants: scumbo (FGSC 49), peak-2a (a mutant known to be allelic to biscuit), and ragged (FGSC 296). Fraction I of all strains studied contains glucose, mannose, and galactose as the main sugars. Uronic acids and amino sugars are also present in small amounts. The glycosidic linkages binding the neutral sugars were analyzed by Lindberg's combined gas chromatography-mass spectrometry techniques for identification of the partially methylated alditol acitate sugar derivatives. The main polymeric portion of fraction I seems to be a linear glucan with the glucose residues linked by 1 leads to 3 and 1 leads to 4 bonds. A mannan portion with a branched configuration is also present, with galactose as the sugar residue which serves as branches in the molecule(s). The branched mannan portion appears to increase in amount in correlation with more drastic morphological changes of the mycelia. In this respect, the mutant ragged has the lowest mycelial growth rate and the largest amount of mannan. The importance of the polysaccharide structure of fraction I on the colonial morphology of the mycelia is discussed.", "contents": "Characterization of the carbohydrate component of fraction I in the Neurospora crassa cell wall. The carbohydrate portion of fraction I of the Neurospora crassa cell wall has been analyzed for sugar composition by gas-liquid chromatography and colorimetric methods. The analysis was performed comparatively in a wild-type strain (RL 3-8A) and three morphological mutants: scumbo (FGSC 49), peak-2a (a mutant known to be allelic to biscuit), and ragged (FGSC 296). Fraction I of all strains studied contains glucose, mannose, and galactose as the main sugars. Uronic acids and amino sugars are also present in small amounts. The glycosidic linkages binding the neutral sugars were analyzed by Lindberg's combined gas chromatography-mass spectrometry techniques for identification of the partially methylated alditol acitate sugar derivatives. The main polymeric portion of fraction I seems to be a linear glucan with the glucose residues linked by 1 leads to 3 and 1 leads to 4 bonds. A mannan portion with a branched configuration is also present, with galactose as the sugar residue which serves as branches in the molecule(s). The branched mannan portion appears to increase in amount in correlation with more drastic morphological changes of the mycelia. In this respect, the mutant ragged has the lowest mycelial growth rate and the largest amount of mannan. The importance of the polysaccharide structure of fraction I on the colonial morphology of the mycelia is discussed."} {"id": "PMID:155687", "title": "Nitrogen metabolite repression of nitrate reductase in Neurospora crassa.", "content": "The effect of different nitrogen compounds on the induction of reduced nicotinamide adenine dinucleotide phosphate-nitrate reductase was examined in Neurospora crassa. Whereas in the wild-type strain several amino acids and ammonia inhibit the formation of nitrate reductase, only glutamine, cysteine, and histidine are shown to inhibit the synthesis of nitrate reductase in a glutamine-requiring auxotroph. None of the amino acids inhibited nitrate reductase activity in vitro. The effects of cysteine and histidine are nonspecific, these amino acids being inhibitory of the growth of the organism. The effect of glutamine on the induction of nitrate reductase is not due to an inhibition of the uptake of the inducer nitrate. By the use of histidine-, pyrimidine-, and arginine-requiring auxotrophs, it was shown that glutamine appears to act per se and does not seem to be converted to another product in order to be effective in repression. The repression of nitrate reductase by ammonia appears, from the results described herein, to be indirect; ammonia has to be converted first to glutamine in order to be effective in repression.", "contents": "Nitrogen metabolite repression of nitrate reductase in Neurospora crassa. The effect of different nitrogen compounds on the induction of reduced nicotinamide adenine dinucleotide phosphate-nitrate reductase was examined in Neurospora crassa. Whereas in the wild-type strain several amino acids and ammonia inhibit the formation of nitrate reductase, only glutamine, cysteine, and histidine are shown to inhibit the synthesis of nitrate reductase in a glutamine-requiring auxotroph. None of the amino acids inhibited nitrate reductase activity in vitro. The effects of cysteine and histidine are nonspecific, these amino acids being inhibitory of the growth of the organism. The effect of glutamine on the induction of nitrate reductase is not due to an inhibition of the uptake of the inducer nitrate. By the use of histidine-, pyrimidine-, and arginine-requiring auxotrophs, it was shown that glutamine appears to act per se and does not seem to be converted to another product in order to be effective in repression. The repression of nitrate reductase by ammonia appears, from the results described herein, to be indirect; ammonia has to be converted first to glutamine in order to be effective in repression."} {"id": "PMID:155688", "title": "Arrangement of the genes coding for ribosomal ribonucleic acids in Neurospora crassa.", "content": "We have cloned and characterized Neurospora crassa ribosomal deoxyribonucleic acid (rDNA). The rDNA is found as a tandemly repeated 6.0-megadalton sequence. We have mapped a portion of the rDNA repeat unit with respect to its sites for 13 restriction endonucleases and defined those regions coding for the 5. 8S, 17S, and 26S ribosomal ribonucleic acids (rRNA's). We have also isolated several clones containing 5S rRNA sequences. The 5S rRNA coding sequences are not found within the rDNA repeat unit. We found that the sequences surrounding the 5S rRNA coding regions are highly heterogeneous.", "contents": "Arrangement of the genes coding for ribosomal ribonucleic acids in Neurospora crassa. We have cloned and characterized Neurospora crassa ribosomal deoxyribonucleic acid (rDNA). The rDNA is found as a tandemly repeated 6.0-megadalton sequence. We have mapped a portion of the rDNA repeat unit with respect to its sites for 13 restriction endonucleases and defined those regions coding for the 5. 8S, 17S, and 26S ribosomal ribonucleic acids (rRNA's). We have also isolated several clones containing 5S rRNA sequences. The 5S rRNA coding sequences are not found within the rDNA repeat unit. We found that the sequences surrounding the 5S rRNA coding regions are highly heterogeneous."} {"id": "PMID:155689", "title": "Transmission of mitochondrial deoxyribonucleic acid in Neurospora crassa sexual crosses.", "content": "Neurospora crassa mitochondrial deoxyribonucleic acid shows strict uniparental inheritance in sexual crosses, with a notable absence of mixtures and recombinant types that appear frequently in heteroplasmons.", "contents": "Transmission of mitochondrial deoxyribonucleic acid in Neurospora crassa sexual crosses. Neurospora crassa mitochondrial deoxyribonucleic acid shows strict uniparental inheritance in sexual crosses, with a notable absence of mixtures and recombinant types that appear frequently in heteroplasmons."} {"id": "PMID:155690", "title": "Spectinomycin dependence in Bacillus subtilis.", "content": "Spectinomycin dependence in Bacillus subtilis involves two mutations, one conferring drug resistance and the other producing a requirement for spectinomycin for growth.", "contents": "Spectinomycin dependence in Bacillus subtilis. Spectinomycin dependence in Bacillus subtilis involves two mutations, one conferring drug resistance and the other producing a requirement for spectinomycin for growth."} {"id": "PMID:155691", "title": "Solubilization of adenosine triphosphatase from membranes of Escherichia coli: effect of p-aminobenzamidine.", "content": "The five subunits of the membrane-bound adenosine triphosphatase (F1) from Escherichia coli were identified on electrophoretograms of membranes which had been washed with a low-ionic-strength buffer containing the protease inhibitor p-aminobenzamidine. All of the subunits of the membrane-bound F1 appeared to have the same molecular weights and isoelectric points as those of the soluble F1, as judged by two-dimensional electrophoresis. p-Aminobenzamidine inhibited the solubilization of F1 rebound to F1-depleted membranes, and was found to inhibit the membrane-bound adenosine triphosphatase activity to a much greater extent than the solubilized activity. It is therefore unlikely that p-aminobenzamidine inhibits the solubilization of F1 by inhibiting a protease, as suggested previously by Cox et al. (G.B. Cox, J.A. Downie, D.R.H. Fayle, F. Gibson, and J. Radik, J. Bacteriol. 133:287--292, 1978).", "contents": "Solubilization of adenosine triphosphatase from membranes of Escherichia coli: effect of p-aminobenzamidine. The five subunits of the membrane-bound adenosine triphosphatase (F1) from Escherichia coli were identified on electrophoretograms of membranes which had been washed with a low-ionic-strength buffer containing the protease inhibitor p-aminobenzamidine. All of the subunits of the membrane-bound F1 appeared to have the same molecular weights and isoelectric points as those of the soluble F1, as judged by two-dimensional electrophoresis. p-Aminobenzamidine inhibited the solubilization of F1 rebound to F1-depleted membranes, and was found to inhibit the membrane-bound adenosine triphosphatase activity to a much greater extent than the solubilized activity. It is therefore unlikely that p-aminobenzamidine inhibits the solubilization of F1 by inhibiting a protease, as suggested previously by Cox et al. (G.B. Cox, J.A. Downie, D.R.H. Fayle, F. Gibson, and J. Radik, J. Bacteriol. 133:287--292, 1978)."} {"id": "PMID:155692", "title": "Inactivation of Neurospora crassa conidia by singlet molecular oxygen generated by a photosensitized reaction.", "content": "Photodynamic damage of Neurospora crassa conidia was studied in the presence of the photosensitizing dye, toluidine blue O. Conidia which germinated to form colonies decreased in number as irradiation time became longer. The photoinactivation of conidia was suppressed by azide, bovine serum albumin, and histidine, and was stimulated in deuterium oxide. Wild-type conidia were less sensitive to the irradiation than albino conidia. In the wild-type, carotenoid-enriched conidia were more resistant against the lethal damage than the conidia which contained small amounts of carotenoids. These results suggest that singlet molecular oxygen causes photodynamic lethal damage to N. crassa conidia and that singlet molecular oxygen is quenched by endogenous carotenoids.", "contents": "Inactivation of Neurospora crassa conidia by singlet molecular oxygen generated by a photosensitized reaction. Photodynamic damage of Neurospora crassa conidia was studied in the presence of the photosensitizing dye, toluidine blue O. Conidia which germinated to form colonies decreased in number as irradiation time became longer. The photoinactivation of conidia was suppressed by azide, bovine serum albumin, and histidine, and was stimulated in deuterium oxide. Wild-type conidia were less sensitive to the irradiation than albino conidia. In the wild-type, carotenoid-enriched conidia were more resistant against the lethal damage than the conidia which contained small amounts of carotenoids. These results suggest that singlet molecular oxygen causes photodynamic lethal damage to N. crassa conidia and that singlet molecular oxygen is quenched by endogenous carotenoids."} {"id": "PMID:155693", "title": "Synthesis and biological activity of an icosapeptide analog of the actomyosin ATPase inhibitory region of troponin I.", "content": "A 20-residue peptide analog of the actomyosin ATPase inhibitory region of rabbit skeletal troponin I (Tn-I) has been synthesized by the solid phase method. The analog exhibited biological activity similar to both Tn-I and a 21-residue cyanogen bromide fragment of Tn-I. At ionic strengths where the inhibition of the actomyosin ATPase due to tropomyosin alone is low, the synthetic peptide in the presence of tropomyosin inhibits 90% of the original ATPase activity. In the absence of tropomyosin, the inhibition due to the peptide is much reduced. In contrast, salmine, a basic protein also known to inhibit the actomyosin ATPase, shows less inhibition in the presence of tropomyosin than it does in its absence. Gel electrophoresis data showed that the enhancement of the analog's inhibition by tropomyosin may be related to the analog's promotion of tropomyosin binding to F-actin similar to that reported for Tn-I and that the reduction of salmine inhibition by tropomyosin may be due to the binding of salmine by tropomyosin. At ionic strengths where binding and inhibition of tropomyosin is significant, the analog enhanced inhibition in a manner similar to that reported for whole Tn-I.", "contents": "Synthesis and biological activity of an icosapeptide analog of the actomyosin ATPase inhibitory region of troponin I. A 20-residue peptide analog of the actomyosin ATPase inhibitory region of rabbit skeletal troponin I (Tn-I) has been synthesized by the solid phase method. The analog exhibited biological activity similar to both Tn-I and a 21-residue cyanogen bromide fragment of Tn-I. At ionic strengths where the inhibition of the actomyosin ATPase due to tropomyosin alone is low, the synthetic peptide in the presence of tropomyosin inhibits 90% of the original ATPase activity. In the absence of tropomyosin, the inhibition due to the peptide is much reduced. In contrast, salmine, a basic protein also known to inhibit the actomyosin ATPase, shows less inhibition in the presence of tropomyosin than it does in its absence. Gel electrophoresis data showed that the enhancement of the analog's inhibition by tropomyosin may be related to the analog's promotion of tropomyosin binding to F-actin similar to that reported for Tn-I and that the reduction of salmine inhibition by tropomyosin may be due to the binding of salmine by tropomyosin. At ionic strengths where binding and inhibition of tropomyosin is significant, the analog enhanced inhibition in a manner similar to that reported for whole Tn-I."} {"id": "PMID:155696", "title": "Assembly of the mitochondrial membrane system. The DNA sequence of a mitochondrial ATPase gene in Saccharomyces cerevisiae.", "content": "The mitochondrial DNA of a cytoplasmic \"petite\" mutant (DS400/A3) of Saccharomyces cerevisiae has been characterized by restriction endonuclease analysis and by DNA sequencing. The DNA has a repeat length of 1,800 base pairs and contains the oli 1 and pho 2 loci, two known markers of the ATPase proteolipid subunit. The nucleotide sequence has helped to establish the presence in the DS400/A3 DNA of the proteolipid gene flanked by two long stretches of DNA rich in A + T. The sequence of the structural gene is in excellent agreement with the previously reported primary structure of the proteolipid. The DNA sequence also indicates that the mitochondrial codons of yeast are highly nondegenerate. The proteolipid gene has been precisely localized on the restriction map of the wild type genome. In addition, it has been possible to orient the gene with respect to other genetic markers and to determine the direction of its transcription.", "contents": "Assembly of the mitochondrial membrane system. The DNA sequence of a mitochondrial ATPase gene in Saccharomyces cerevisiae. The mitochondrial DNA of a cytoplasmic \"petite\" mutant (DS400/A3) of Saccharomyces cerevisiae has been characterized by restriction endonuclease analysis and by DNA sequencing. The DNA has a repeat length of 1,800 base pairs and contains the oli 1 and pho 2 loci, two known markers of the ATPase proteolipid subunit. The nucleotide sequence has helped to establish the presence in the DS400/A3 DNA of the proteolipid gene flanked by two long stretches of DNA rich in A + T. The sequence of the structural gene is in excellent agreement with the previously reported primary structure of the proteolipid. The DNA sequence also indicates that the mitochondrial codons of yeast are highly nondegenerate. The proteolipid gene has been precisely localized on the restriction map of the wild type genome. In addition, it has been possible to orient the gene with respect to other genetic markers and to determine the direction of its transcription."} {"id": "PMID:155697", "title": "On the mechanism of Ca2+-dependent adenosine triphosphatase of sarcoplasmic reticulum. Occurrence of two types of phosphoenzyme intermediates in the presence of KCl.", "content": "The steady state kinetics of ATP hydrolysis by partially purified adenosine triphosphatase preparations of sarcoplasmic reticulum was investigated at 0 degrees C and pH 7.0 in 2.0 mM MgCl2, 20 microM [gamma-32P]ATP, 20 microM CaCl2, and various concentrations of KCl in the presence and absence of 12% dimethyl sulfoxide. The steady state phosphoenzyme formed under these conditions could be resolved kinetically into ADP-sensitive and ADP-insensitive forms. These steady state kinetic data were analyzed according to a scheme in which the ADP-sensitive and ADP-insensitive phosphoenzymes occur sequentially, and Pi is derived from the latter. The KCl-dependent turnover rate of the ADP-insensitive phosphoenzyme that was estimated according to this scheme was in good agreement with the directly measured hydrolysis rate constant of the ADP-insensitive phosphoenzyme. In addition, the time course of the decomposition of the total amount of phosphoenzyme, measured after a steady state level was reached in 20 mM KCl and further phosphorylation was prevented by addition of excess ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid, was also in agreement with that calculated according to this scheme using values of the rate constants estimated from the amounts of the ADP-sensitive and ADP-insensitive phosphoenzymes and the rate of ATP hydrolysis. These results, together with our previous findings, support the view that this scheme describes the mechanism of ATP hydrolysis in the presence of KCl.", "contents": "On the mechanism of Ca2+-dependent adenosine triphosphatase of sarcoplasmic reticulum. Occurrence of two types of phosphoenzyme intermediates in the presence of KCl. The steady state kinetics of ATP hydrolysis by partially purified adenosine triphosphatase preparations of sarcoplasmic reticulum was investigated at 0 degrees C and pH 7.0 in 2.0 mM MgCl2, 20 microM [gamma-32P]ATP, 20 microM CaCl2, and various concentrations of KCl in the presence and absence of 12% dimethyl sulfoxide. The steady state phosphoenzyme formed under these conditions could be resolved kinetically into ADP-sensitive and ADP-insensitive forms. These steady state kinetic data were analyzed according to a scheme in which the ADP-sensitive and ADP-insensitive phosphoenzymes occur sequentially, and Pi is derived from the latter. The KCl-dependent turnover rate of the ADP-insensitive phosphoenzyme that was estimated according to this scheme was in good agreement with the directly measured hydrolysis rate constant of the ADP-insensitive phosphoenzyme. In addition, the time course of the decomposition of the total amount of phosphoenzyme, measured after a steady state level was reached in 20 mM KCl and further phosphorylation was prevented by addition of excess ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid, was also in agreement with that calculated according to this scheme using values of the rate constants estimated from the amounts of the ADP-sensitive and ADP-insensitive phosphoenzymes and the rate of ATP hydrolysis. These results, together with our previous findings, support the view that this scheme describes the mechanism of ATP hydrolysis in the presence of KCl."} {"id": "PMID:155698", "title": "Binding phenomena of isolated unique plasmic degradation products of human cross-linked fibrin.", "content": "Proteolysis of human cross-linked fibrin by plasmin results in the formation of a DD . E complex, and Fragments DD and E as the major degradation products. Three species of Fragment E, which differ both in molecular weights (E1, Mr = 60,000; E2, Mr = 55,000; E3, Mr = 50,000) and in charge, have been isolated from a digest of cross-linked fibrin. Each Fragment E species reacts with monospecific anti-E antiserum. Fragments E1 and E2 bind with Fragment DD to form a DD . E complex but Fragment E3 is inactive. This binding is specific since these Fragments E do not bind to fibrinogen or to degradation products of fibrinogen or of noncross-linked fibrin. Fragments E1 and E2 incubated with plasmin are degraded to Fragment E3, suggesting that the three species represent sequential degradation products. Plasmin-treated Fragments E1 and E2 no longer bind with Fragment DD; therefore, it appears that the peptides cleaved from Fragment E2 by plasmin contain or modify the sites responsible for complex formation. On the other hand, Fragment DD binds not only to Fragments E1 and E2, but also to fibrinogen, Fragments X (Stage 1), X (Stage 2), Y, and NH2-terminal disulfide knot, but only after thrombin treatment, suggesting that Fragment DD binds to complementary sites on the NH2-terminal region of fibrinogen which are exposed after thrombin treatment.", "contents": "Binding phenomena of isolated unique plasmic degradation products of human cross-linked fibrin. Proteolysis of human cross-linked fibrin by plasmin results in the formation of a DD . E complex, and Fragments DD and E as the major degradation products. Three species of Fragment E, which differ both in molecular weights (E1, Mr = 60,000; E2, Mr = 55,000; E3, Mr = 50,000) and in charge, have been isolated from a digest of cross-linked fibrin. Each Fragment E species reacts with monospecific anti-E antiserum. Fragments E1 and E2 bind with Fragment DD to form a DD . E complex but Fragment E3 is inactive. This binding is specific since these Fragments E do not bind to fibrinogen or to degradation products of fibrinogen or of noncross-linked fibrin. Fragments E1 and E2 incubated with plasmin are degraded to Fragment E3, suggesting that the three species represent sequential degradation products. Plasmin-treated Fragments E1 and E2 no longer bind with Fragment DD; therefore, it appears that the peptides cleaved from Fragment E2 by plasmin contain or modify the sites responsible for complex formation. On the other hand, Fragment DD binds not only to Fragments E1 and E2, but also to fibrinogen, Fragments X (Stage 1), X (Stage 2), Y, and NH2-terminal disulfide knot, but only after thrombin treatment, suggesting that Fragment DD binds to complementary sites on the NH2-terminal region of fibrinogen which are exposed after thrombin treatment."} {"id": "PMID:155699", "title": "A comparative study of poly(glycolic acid) and catgut as suture materials. Histomorphology and mechanical properties.", "content": "The \"quality\" of poly(glycolic acid) as an absorbable suture material was investigated in comparison with catgut. Tissue reactions to poly(glycolic acid) and plain catgut were examined histomorphologically at different time intervals after implantation in rats, and compared. Four mechanical properties were also examined as relevant quality factors: elastic stiffness, tensile strength, toughness, and percent elongation at rupture of the suture material per se (unknotted). The variation of these properties in poly(glycolic acid) implants was followed since their insertion in the tissues. Histological behavior and mechanical properties appear to be more closely correlated in the case of poly(glycolic acid) than in the case of catgut, as a consequence of a greater regularity of tissue reaction towards the synthetic material. Both tissue reaction and tensile properties variation are independent of size in the case of the braided poly(glycolic acid) sutures examined. Elastic stiffness and tensile strength decrease steadily in time; toughness and ultimate elongation display an increase up to a maximum within one day since implantation, and then decrease.", "contents": "A comparative study of poly(glycolic acid) and catgut as suture materials. Histomorphology and mechanical properties. The \"quality\" of poly(glycolic acid) as an absorbable suture material was investigated in comparison with catgut. Tissue reactions to poly(glycolic acid) and plain catgut were examined histomorphologically at different time intervals after implantation in rats, and compared. Four mechanical properties were also examined as relevant quality factors: elastic stiffness, tensile strength, toughness, and percent elongation at rupture of the suture material per se (unknotted). The variation of these properties in poly(glycolic acid) implants was followed since their insertion in the tissues. Histological behavior and mechanical properties appear to be more closely correlated in the case of poly(glycolic acid) than in the case of catgut, as a consequence of a greater regularity of tissue reaction towards the synthetic material. Both tissue reaction and tensile properties variation are independent of size in the case of the braided poly(glycolic acid) sutures examined. Elastic stiffness and tensile strength decrease steadily in time; toughness and ultimate elongation display an increase up to a maximum within one day since implantation, and then decrease."} {"id": "PMID:155701", "title": "Real time observation of left atrial myxoma with high speed B mode echocardiography.", "content": "Four patients with left atrial myxoma were studied using high speed B mode echocardiography with a mechanical sector scanning system. In all four patients, a mass of echoes was recognized in the left atrial chamber during systole. Its lower portion protruded into the left ventricle through the mitral orifice in diastole. The degree of protrusion of the tumor echo varied. An analysis of three cross sections, long axis of left ventricle, sagittal and horizontal axes, showed that the tumor moved anterosuperiorly to posteroinferiorly in the left-sided heart chambers. Its movement was clearly observed in real time. The echo pattern from the tumor had an appearance of mottling, not layering. The myxomas were successfully removed from the left atrial chambers by surgical intervention in all cases.", "contents": "Real time observation of left atrial myxoma with high speed B mode echocardiography. Four patients with left atrial myxoma were studied using high speed B mode echocardiography with a mechanical sector scanning system. In all four patients, a mass of echoes was recognized in the left atrial chamber during systole. Its lower portion protruded into the left ventricle through the mitral orifice in diastole. The degree of protrusion of the tumor echo varied. An analysis of three cross sections, long axis of left ventricle, sagittal and horizontal axes, showed that the tumor moved anterosuperiorly to posteroinferiorly in the left-sided heart chambers. Its movement was clearly observed in real time. The echo pattern from the tumor had an appearance of mottling, not layering. The myxomas were successfully removed from the left atrial chambers by surgical intervention in all cases."} {"id": "PMID:155702", "title": "Gray scale ultrasound in adnexal thickening: correlation with laparoscopy.", "content": "A retrospective comparison between ultrasound and subsequent laparoscopy was made in 70 female patients to evaluate the sonographic features of minimal pelvic disease (in particular, adnexal thickening). The overall accuracy of sonography as compared with laparoscopy was 75 percent (53 of 70), with a true positive rate of 72 percent (40 of 51) and a true negative rate of 68 percent (13 of 19). In this study the concept of clinical or sonographic adnexal thickening did not correlate with observations at laparoscopy. Of the 7 patients diagnosed by ultrasound as having adnexal thickening, only 1 had pelvic inflammatory disease, whereas the other 6 showed no abnormalities at laparoscopy.", "contents": "Gray scale ultrasound in adnexal thickening: correlation with laparoscopy. A retrospective comparison between ultrasound and subsequent laparoscopy was made in 70 female patients to evaluate the sonographic features of minimal pelvic disease (in particular, adnexal thickening). The overall accuracy of sonography as compared with laparoscopy was 75 percent (53 of 70), with a true positive rate of 72 percent (40 of 51) and a true negative rate of 68 percent (13 of 19). In this study the concept of clinical or sonographic adnexal thickening did not correlate with observations at laparoscopy. Of the 7 patients diagnosed by ultrasound as having adnexal thickening, only 1 had pelvic inflammatory disease, whereas the other 6 showed no abnormalities at laparoscopy."} {"id": "PMID:155700", "title": "Standardization of parameters in follow-up study after mitral commissurotomy.", "content": "Two-hundred and fifty-five patients were followed up to maximum 19 years (1879 patient-years) after mitral commissurotomy by means of either the finger fracture, transventricular dilator or open method. During this period of time, patients were asked to answer a questionnaire and to be examined at 2 to 3 years intervals. Twenty-two late deaths and 17 reoperations were encountered, and significant differences according to operative methods were observed in the survival and reoperation-free curves. Values from CTR, Rv1 + Sv5/Rv5 + Sv1 ratio, LAMP and DDR were standardized, and each standard value showed a tendency of significant improvement followed by gradual deterioration after commissurotomy even in patients with normal social activities. Parameters from patients reoperated on were compared with standard values, and statistically significant differences were noted. It would be concluded that standardization of parameters is of a great importance in follow-up study after mitral commissurotomy especially to establish indications to reoperation most adequately.", "contents": "Standardization of parameters in follow-up study after mitral commissurotomy. Two-hundred and fifty-five patients were followed up to maximum 19 years (1879 patient-years) after mitral commissurotomy by means of either the finger fracture, transventricular dilator or open method. During this period of time, patients were asked to answer a questionnaire and to be examined at 2 to 3 years intervals. Twenty-two late deaths and 17 reoperations were encountered, and significant differences according to operative methods were observed in the survival and reoperation-free curves. Values from CTR, Rv1 + Sv5/Rv5 + Sv1 ratio, LAMP and DDR were standardized, and each standard value showed a tendency of significant improvement followed by gradual deterioration after commissurotomy even in patients with normal social activities. Parameters from patients reoperated on were compared with standard values, and statistically significant differences were noted. It would be concluded that standardization of parameters is of a great importance in follow-up study after mitral commissurotomy especially to establish indications to reoperation most adequately."} {"id": "PMID:155705", "title": "Inclusion of a program of instruction in care of the disabled in a dental school curriculum.", "content": "Lack of practitioner training is considered a major reason for dental neglect of disabled persons. The feasibility of instruction in the care of the disabled for dental and dental hygiene students at the undergraduate level was demonstrated in a prototype program encompassing a continuum of didactic courses, clinical experiences in extramural and intramural settings, inservice training and continuing education, interdisciplinary activities, and evaluative research. Successful implementation of such a program required developing and using appropriate support systems, such as instructional materials, social services, public relations, and monitoring of care delivery. A format combining specific courses with inclusion of disability subject matter in existing courses appeared to be advantageous in intergrating the program into the dental curriculum. Evaluation data indicated the value of undergraduate training in improving access to dental care for the disabled patient.", "contents": "Inclusion of a program of instruction in care of the disabled in a dental school curriculum. Lack of practitioner training is considered a major reason for dental neglect of disabled persons. The feasibility of instruction in the care of the disabled for dental and dental hygiene students at the undergraduate level was demonstrated in a prototype program encompassing a continuum of didactic courses, clinical experiences in extramural and intramural settings, inservice training and continuing education, interdisciplinary activities, and evaluative research. Successful implementation of such a program required developing and using appropriate support systems, such as instructional materials, social services, public relations, and monitoring of care delivery. A format combining specific courses with inclusion of disability subject matter in existing courses appeared to be advantageous in intergrating the program into the dental curriculum. Evaluation data indicated the value of undergraduate training in improving access to dental care for the disabled patient."} {"id": "PMID:155706", "title": "Assessment of student attitude and confidence in a program of dental education in care of the disabled.", "content": "An analysis is presented of the effect of a four-year dental school program in care of the disabled on expressed student attitude and confidence towards treating the handicapped patient. The longitudinal study, involving 503 students in six dental classes, revealed a willingness by the majority of students (greater than or equal to 60 percent) to treat pateints with whom they feel capable. This attitude remained essentially unaffected by the program. In contrast, levels of students' perceived confidence in treating handicapped persons increased significantly as the result of specific instruction in disability management; heightened confidence levels were sustained for one academic year. Expressed ability to treat the disabled appeared to increase for successive classes. The result support the premise that dental graduates who have received instruction in disability care will fell more confident and hence will be more likely to treat patients with special needs.", "contents": "Assessment of student attitude and confidence in a program of dental education in care of the disabled. An analysis is presented of the effect of a four-year dental school program in care of the disabled on expressed student attitude and confidence towards treating the handicapped patient. The longitudinal study, involving 503 students in six dental classes, revealed a willingness by the majority of students (greater than or equal to 60 percent) to treat pateints with whom they feel capable. This attitude remained essentially unaffected by the program. In contrast, levels of students' perceived confidence in treating handicapped persons increased significantly as the result of specific instruction in disability management; heightened confidence levels were sustained for one academic year. Expressed ability to treat the disabled appeared to increase for successive classes. The result support the premise that dental graduates who have received instruction in disability care will fell more confident and hence will be more likely to treat patients with special needs."} {"id": "PMID:155707", "title": "The effect of supplemental lecture, evaluation method and instructional type on student performance in a preclinical technique project.", "content": "This study examined two types of instruction, two methods of evaluation, and the effects of a supplemental lecture in teaching a laboratory technique exercise. Students were randomly assigned to one of four groups: (1) self-instruction, self-evaluation; (2) self-instruction, teacher-evaluation; (3) teacher-aided instruction, self evaluation; and (4) teacher-aided instruction, teacher-evaluation. In addition, half of the students in each of the four groups received a supplemental lecture. Ratings of technical performance, a didactic posttest, and project completion time, were used as outcome measures. Of 27 main treatment effects tested, 25 demonstrated no significant differences. This study fails to demonstrate any major advantage of using self versus traditional forms of instruction and evaluation when student performance is the primary consideration.", "contents": "The effect of supplemental lecture, evaluation method and instructional type on student performance in a preclinical technique project. This study examined two types of instruction, two methods of evaluation, and the effects of a supplemental lecture in teaching a laboratory technique exercise. Students were randomly assigned to one of four groups: (1) self-instruction, self-evaluation; (2) self-instruction, teacher-evaluation; (3) teacher-aided instruction, self evaluation; and (4) teacher-aided instruction, teacher-evaluation. In addition, half of the students in each of the four groups received a supplemental lecture. Ratings of technical performance, a didactic posttest, and project completion time, were used as outcome measures. Of 27 main treatment effects tested, 25 demonstrated no significant differences. This study fails to demonstrate any major advantage of using self versus traditional forms of instruction and evaluation when student performance is the primary consideration."} {"id": "PMID:155708", "title": "Assessment of allergy to local anesthetics.", "content": "Regional analgesia is much too important to be denied to patients on the basis of questionable allergic histories. Often, adverse reactions can be traced directly to the pharmacologic properties of the agents involved. The dentist must adequately distinguish these reactions from those directly related to allergic phenomena. For the comprehensive management of patients with allergic histories, the significance as well as the limitations of intracutaneous skin testing must be appreciated. The practitioner should recognize the need, make proper referrals, and interpret the results of skin tests appropriately. Hopefully, this report has served to disperse the confusion surrounding local anesthetic hypersensitivity and will enable more dentists to proceed with confidence in the assessment and management of their allergic patients.", "contents": "Assessment of allergy to local anesthetics. Regional analgesia is much too important to be denied to patients on the basis of questionable allergic histories. Often, adverse reactions can be traced directly to the pharmacologic properties of the agents involved. The dentist must adequately distinguish these reactions from those directly related to allergic phenomena. For the comprehensive management of patients with allergic histories, the significance as well as the limitations of intracutaneous skin testing must be appreciated. The practitioner should recognize the need, make proper referrals, and interpret the results of skin tests appropriately. Hopefully, this report has served to disperse the confusion surrounding local anesthetic hypersensitivity and will enable more dentists to proceed with confidence in the assessment and management of their allergic patients."} {"id": "PMID:155709", "title": "Primary inoculation tuberculosis.", "content": "A case of primary inoculation tuberculosis of the finger is described, in which Mantoux test conversion reverted after prompt surgical and medical treatment. The pathology of primary inoculation tuberculosis is reviewed briefly, and the rationale for excision of the early tuberculous lesion is discussed.", "contents": "Primary inoculation tuberculosis. A case of primary inoculation tuberculosis of the finger is described, in which Mantoux test conversion reverted after prompt surgical and medical treatment. The pathology of primary inoculation tuberculosis is reviewed briefly, and the rationale for excision of the early tuberculous lesion is discussed."} {"id": "PMID:155713", "title": "False positive 51Cr release tests during post-transplant immunological monitoring due to recipient serum radioactive contamination.", "content": "The occurrence of false positive 51Cr release test results in post-transplant immunological monitoring of human kidney graft recipients due to 131I carryover from renograms is described. False positivity was detected in 7 instances in 4 recipients, and suspected in 12 instances in 7 recipients, in a series of 46 consecutive transplant recipients. Technical methods and controls to detect and prevent such false positivity are described.", "contents": "False positive 51Cr release tests during post-transplant immunological monitoring due to recipient serum radioactive contamination. The occurrence of false positive 51Cr release test results in post-transplant immunological monitoring of human kidney graft recipients due to 131I carryover from renograms is described. False positivity was detected in 7 instances in 4 recipients, and suspected in 12 instances in 7 recipients, in a series of 46 consecutive transplant recipients. Technical methods and controls to detect and prevent such false positivity are described."} {"id": "PMID:155714", "title": "The value of plasmid studies in the epidemiology of infections due to drug-resistant Salmonella wien.", "content": "Since 1969 strains of Salmonella wien that are resistant to multiple antibacterial drugs have caused widespread epidemics of enteritis in Europe and North Africa. Of 113 British strains examined between January 1970 and January 1977, 67 were multi-resistant. These strains and 22 strains from six other countries were examined to determine their plasmid content. Two plasmids were found in the vast majority of strains: an FIme factor, conferring resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, spectinomycin, sulfonamides, and tetracyclines (ACKSSpSuT), and a nonautotransferring plasmid of resistance type ASSu. The FIme plasmids have dual incompatibility: they are incompatible with group FI factors and with the MP10 plasmid of Salmonella typhimurium, which belongs to a separate group. Other plasmids found in S. wien included principally a ColIa factor and an autotransferring plasmid that codes for ampicillin resistance and belongs to compatibility group I2. The similarity in plasmid content of strains isolated in widely separated areas suggests that they have a clonal origin.", "contents": "The value of plasmid studies in the epidemiology of infections due to drug-resistant Salmonella wien. Since 1969 strains of Salmonella wien that are resistant to multiple antibacterial drugs have caused widespread epidemics of enteritis in Europe and North Africa. Of 113 British strains examined between January 1970 and January 1977, 67 were multi-resistant. These strains and 22 strains from six other countries were examined to determine their plasmid content. Two plasmids were found in the vast majority of strains: an FIme factor, conferring resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, spectinomycin, sulfonamides, and tetracyclines (ACKSSpSuT), and a nonautotransferring plasmid of resistance type ASSu. The FIme plasmids have dual incompatibility: they are incompatible with group FI factors and with the MP10 plasmid of Salmonella typhimurium, which belongs to a separate group. Other plasmids found in S. wien included principally a ColIa factor and an autotransferring plasmid that codes for ampicillin resistance and belongs to compatibility group I2. The similarity in plasmid content of strains isolated in widely separated areas suggests that they have a clonal origin."} {"id": "PMID:155716", "title": "Acute effects of streptozotocin diabetes on rat renal function.", "content": "Renal clearance studies were performed on rats both during the administration of streptozotocin and sequentially during the following 8 days as hyperglycemia progressed. Although GFR was depressed 30 min after the drug administration, GFR steadily rose during the following days to become 52% greater than control levels. Renal size did not change during this short period, and it is suggested that glomerular hemodynamic changes are responsible. A maximal tubular reabsorptive capacity for glucose (TmG) could not be satisfactorily demonstrated in normal rats, although glucose reabsorption was significantly depressed at high-filtered loads. At comparable filtered loads, glucose reabsorption in diabetic rats was almost complete in contrast to normal rats, and the increases in GFR and renal tubular sodium reabsorption are presumed to be the major factors. The administration of insulin to normal and diabetic rats was followed by a significant diuresis as well as an increase of 1% to 4% in the fraction of filtered sodium excreted although GFR was unaltered. This shows that even a 35% to 60% reduction in the filtered load of glucose can significantly depress renal sodium reabsorption. It is concluded that this is a good animal model in which to study the effects of diabetes on renal function as well as the in vivo interrelationships of sodium and glucose reabsorption.", "contents": "Acute effects of streptozotocin diabetes on rat renal function. Renal clearance studies were performed on rats both during the administration of streptozotocin and sequentially during the following 8 days as hyperglycemia progressed. Although GFR was depressed 30 min after the drug administration, GFR steadily rose during the following days to become 52% greater than control levels. Renal size did not change during this short period, and it is suggested that glomerular hemodynamic changes are responsible. A maximal tubular reabsorptive capacity for glucose (TmG) could not be satisfactorily demonstrated in normal rats, although glucose reabsorption was significantly depressed at high-filtered loads. At comparable filtered loads, glucose reabsorption in diabetic rats was almost complete in contrast to normal rats, and the increases in GFR and renal tubular sodium reabsorption are presumed to be the major factors. The administration of insulin to normal and diabetic rats was followed by a significant diuresis as well as an increase of 1% to 4% in the fraction of filtered sodium excreted although GFR was unaltered. This shows that even a 35% to 60% reduction in the filtered load of glucose can significantly depress renal sodium reabsorption. It is concluded that this is a good animal model in which to study the effects of diabetes on renal function as well as the in vivo interrelationships of sodium and glucose reabsorption."} {"id": "PMID:155728", "title": "Sulphur and phosphorus content in relation to fibre composition and atrophy of skeletal muscle in patients with Parkinson's disease.", "content": "Seventeen patients with Parkinson's disease have been compared with 8 normal individuals by biopsy of either the biceps brachii or quadriceps femoris muscles. All biopsies were investigated by enzyme histochemistry. With 13 patients, as well as all controls, scanning electron microscopy with X-ray microanalysis was employed on cryo-sections adjacent to those prepared for light microscopy. Thus, the elemental composition of single muscle fibres was obtained and could be related to histochemical fibre types. Fibre type analysis on the diseased material, based on differential stainability for alkali- and acid-stable ATPase, showed a normal type I and type IIA fibre frequency. A mild type IIB dominance at the expense of type IIA fibres was regarded as a significant deviation from normal. A slight to moderate muscle atrophy affected type IIB fibres almost exclusively. Normal content of sulphur and phosphorus was detected in type I and type IIA Fibres but a lowered sulphur content was obvious in type IIB fibres, especially in the atrophic ones, which also exhibited an increase in phosphorus content. The shift in fibre composition from IIA to IIB, the type IIB fibre atrophy and the change in sulphur and phosphorus content of type IIB fibres are interpreted as signs of a disuse which preferentially affects fast twitch type IIB motor units. These presumably have the highest threshold for activation under pathological conditions characterized by increased muscular tone and difficulties in the performance of rapid and strong voluntary movements.", "contents": "Sulphur and phosphorus content in relation to fibre composition and atrophy of skeletal muscle in patients with Parkinson's disease. Seventeen patients with Parkinson's disease have been compared with 8 normal individuals by biopsy of either the biceps brachii or quadriceps femoris muscles. All biopsies were investigated by enzyme histochemistry. With 13 patients, as well as all controls, scanning electron microscopy with X-ray microanalysis was employed on cryo-sections adjacent to those prepared for light microscopy. Thus, the elemental composition of single muscle fibres was obtained and could be related to histochemical fibre types. Fibre type analysis on the diseased material, based on differential stainability for alkali- and acid-stable ATPase, showed a normal type I and type IIA fibre frequency. A mild type IIB dominance at the expense of type IIA fibres was regarded as a significant deviation from normal. A slight to moderate muscle atrophy affected type IIB fibres almost exclusively. Normal content of sulphur and phosphorus was detected in type I and type IIA Fibres but a lowered sulphur content was obvious in type IIB fibres, especially in the atrophic ones, which also exhibited an increase in phosphorus content. The shift in fibre composition from IIA to IIB, the type IIB fibre atrophy and the change in sulphur and phosphorus content of type IIB fibres are interpreted as signs of a disuse which preferentially affects fast twitch type IIB motor units. These presumably have the highest threshold for activation under pathological conditions characterized by increased muscular tone and difficulties in the performance of rapid and strong voluntary movements."} {"id": "PMID:155729", "title": "An ultrastructural study of nerve terminal degeneration in muscle spindles of the tenuissimus muscle of the cat.", "content": "Muscle spindles in the tenuissimus muscle of the cat were studied between 12 and 168 h after cutting or freezing the nerve to this muscle. Degenerative changes in sensory and motor nerve terminals on intrafusal muscle fibres were observed using the electron microscope. Comparisons were made with spindles from unoperated or sham-operated cats. The earliest degenerative changes were seen in sensory and motor terminals at 20-24 h after the lesion. No nerve endings were seen by 114 h after denervation. The most consistent initial signs of degeneration were: (1) the presence of abnormal mitochondria and dense bodies in sensory terminals, and (2) a decrease in the number and clumping of synaptic vesicles combined with an increase in glycogen and neurofilaments in motor endings. Intrafusal fibres participate in the removal of degenerating sensory endings. Schwann cells phagocytose degenerating motor terminals. The disappearance of nerve terminals precedes the complete degeneration of preterminal myelinated fibres within the muscle spindle.", "contents": "An ultrastructural study of nerve terminal degeneration in muscle spindles of the tenuissimus muscle of the cat. Muscle spindles in the tenuissimus muscle of the cat were studied between 12 and 168 h after cutting or freezing the nerve to this muscle. Degenerative changes in sensory and motor nerve terminals on intrafusal muscle fibres were observed using the electron microscope. Comparisons were made with spindles from unoperated or sham-operated cats. The earliest degenerative changes were seen in sensory and motor terminals at 20-24 h after the lesion. No nerve endings were seen by 114 h after denervation. The most consistent initial signs of degeneration were: (1) the presence of abnormal mitochondria and dense bodies in sensory terminals, and (2) a decrease in the number and clumping of synaptic vesicles combined with an increase in glycogen and neurofilaments in motor endings. Intrafusal fibres participate in the removal of degenerating sensory endings. Schwann cells phagocytose degenerating motor terminals. The disappearance of nerve terminals precedes the complete degeneration of preterminal myelinated fibres within the muscle spindle."} {"id": "PMID:155741", "title": "Stereochemical preferences for curarimimetic neuromuscular junction blockade IV: Monoquaternary ammonium probes possessing carbon and nitrogen asymmetry.", "content": "Two enantiomeric pairs of neuromuscular junction blocking agents were prepared in which an asymmetric carbon atom is adjacent to an asymmetric quaternized nitrogen moiety. The blocking agents were obtained from the enantiomers of laudanosine by stereoselective quaternization with benzyl and ethyl iodides. Curarimimetic potencies were measured with an in vivo cat hypoglossal nerve-tongue muscle preparation. The studies suggest that the asymmetry present in these structures does not lead to significant differences in blocking potency between enantiomers.", "contents": "Stereochemical preferences for curarimimetic neuromuscular junction blockade IV: Monoquaternary ammonium probes possessing carbon and nitrogen asymmetry. Two enantiomeric pairs of neuromuscular junction blocking agents were prepared in which an asymmetric carbon atom is adjacent to an asymmetric quaternized nitrogen moiety. The blocking agents were obtained from the enantiomers of laudanosine by stereoselective quaternization with benzyl and ethyl iodides. Curarimimetic potencies were measured with an in vivo cat hypoglossal nerve-tongue muscle preparation. The studies suggest that the asymmetry present in these structures does not lead to significant differences in blocking potency between enantiomers."} {"id": "PMID:155742", "title": "Transport of organic ions in renal cortical luminal and antiluminal membrane vesicles.", "content": "Based upon saturability, kinetic analysis and specific inhibition, specific transport for the organic anion, p-aminohippurate was found in isolated luminal and antiluminal membrane vesicles from dog kidney cortex. The transport for organic anions in the two membranes differed from one another on the basis of kinetic parameters ((Km, Vmax and Ki for probenecid) and counterflow phenomenon (only the antiluminal membrane displayed the capacity to accelerate the exchange of p-aminohippurate). Also described is specific transport for the organic cation N1 methylnicotinamide in each membrane. The luminal and antiluminal transport of N1-methylnicotinamide are distinguished from one another by kinetic parameters (Km, Vmax and Ki for Darstine) and counterflow data (counterflow of N1-methylnicotinamide was observed only in the luminal membrane). The results are discussed in view of a proposed model to explain transepithelial transport of these organic ions.", "contents": "Transport of organic ions in renal cortical luminal and antiluminal membrane vesicles. Based upon saturability, kinetic analysis and specific inhibition, specific transport for the organic anion, p-aminohippurate was found in isolated luminal and antiluminal membrane vesicles from dog kidney cortex. The transport for organic anions in the two membranes differed from one another on the basis of kinetic parameters ((Km, Vmax and Ki for probenecid) and counterflow phenomenon (only the antiluminal membrane displayed the capacity to accelerate the exchange of p-aminohippurate). Also described is specific transport for the organic cation N1 methylnicotinamide in each membrane. The luminal and antiluminal transport of N1-methylnicotinamide are distinguished from one another by kinetic parameters (Km, Vmax and Ki for Darstine) and counterflow data (counterflow of N1-methylnicotinamide was observed only in the luminal membrane). The results are discussed in view of a proposed model to explain transepithelial transport of these organic ions."} {"id": "PMID:155745", "title": "Renal impairment in urate excretion in patients with Down's syndrome.", "content": "Uric acid and creatinine clearance studies were performed in nine subjects with Down's syndrome and in eight mentally retarded controls. The urate clearance was significantly decreased in subjects with Down's syndrome compared with controls. Their mean creatinine clearances were also significantly lower than the controls. No significant differences were shown in erythrocyte lactate dehydrogenase activity, in blood lactate and in blood beta-hydroxybutyrate levels between 20 subjects with Down's syndrome and 16 controls. Glomerular dysfunction would seem to contribute to hyperuricemia in Down's syndrome.", "contents": "Renal impairment in urate excretion in patients with Down's syndrome. Uric acid and creatinine clearance studies were performed in nine subjects with Down's syndrome and in eight mentally retarded controls. The urate clearance was significantly decreased in subjects with Down's syndrome compared with controls. Their mean creatinine clearances were also significantly lower than the controls. No significant differences were shown in erythrocyte lactate dehydrogenase activity, in blood lactate and in blood beta-hydroxybutyrate levels between 20 subjects with Down's syndrome and 16 controls. Glomerular dysfunction would seem to contribute to hyperuricemia in Down's syndrome."} {"id": "PMID:155751", "title": "Evidence for multiple sites of regulation of heme synthesis in murine erythroleukemia cells.", "content": "Friend murine erythroleukemia (MEL) cells can be induced to differentiate along the erythroid pathway by such dissimilar agents as dimethyl sulfoxide (DMSO), butyrate, inhibitors of DNA synthesis, and certain highly polar agents. This study showed differential biochemical effects of the potent inducers DMSO and butyrate on the heme biosynthetic pathway in three clones of Friend MEL cells. When the cells were incubated with combinations of DMSO and butyrate, hemoglobin production was less than that amount produced when each inducer was incubated singly with the cells. Procaine, a local anesthetic that competes with Ca2+ and thus affects membrane permeability, slightly inhibited DMSO-mediated hemoglobin production but almost tripled the level stimulated by butyrate alone. Similarly, EDTA, which also can bind Ca2+ and which can modify the activity of heme biosynthetic enzymes, also inhibited hemoglobin production mediated by DMSO, whereas it stimulated hemoglobin production in cells exposed to butyrate. Total porphyrin accumulation was greater in DMSO-treated cells than in butyrate-treated cells, which suggests that butyrate induces the enzymes of the heme pathway more efficiently than does DMSO. DMSO and butyrate may affect the heme biosynthetic pathway by multiple mechanisms or, alternatively, they may affect the multistep pathway at various points, producing partial blocks or incomplete enzyme induction.", "contents": "Evidence for multiple sites of regulation of heme synthesis in murine erythroleukemia cells. Friend murine erythroleukemia (MEL) cells can be induced to differentiate along the erythroid pathway by such dissimilar agents as dimethyl sulfoxide (DMSO), butyrate, inhibitors of DNA synthesis, and certain highly polar agents. This study showed differential biochemical effects of the potent inducers DMSO and butyrate on the heme biosynthetic pathway in three clones of Friend MEL cells. When the cells were incubated with combinations of DMSO and butyrate, hemoglobin production was less than that amount produced when each inducer was incubated singly with the cells. Procaine, a local anesthetic that competes with Ca2+ and thus affects membrane permeability, slightly inhibited DMSO-mediated hemoglobin production but almost tripled the level stimulated by butyrate alone. Similarly, EDTA, which also can bind Ca2+ and which can modify the activity of heme biosynthetic enzymes, also inhibited hemoglobin production mediated by DMSO, whereas it stimulated hemoglobin production in cells exposed to butyrate. Total porphyrin accumulation was greater in DMSO-treated cells than in butyrate-treated cells, which suggests that butyrate induces the enzymes of the heme pathway more efficiently than does DMSO. DMSO and butyrate may affect the heme biosynthetic pathway by multiple mechanisms or, alternatively, they may affect the multistep pathway at various points, producing partial blocks or incomplete enzyme induction."} {"id": "PMID:155752", "title": "Technique for preclinical evaluation of continuous infusion chemotherapy with the use of WF rat acute myelogenous leukemia.", "content": "A technique was developed for continuous iv infusion chemotherapy in an inbred rat model of acute myelogenous leukemia. Polyethylene tubing was inserted surgically into the internal jugular vein of adult WF rats, burrowed sc to the base of the tail, and connected to an infusion pump. A flexible spring was sutured at the base of the tail and fastened to the cage wall; it protected the infusion catheter and allowed movement of the rat within the cage. This technique was used to compare bolus with continuous infusion therapy with adriamycin, cytosine arabinoside, and neocarzinostatin. Only small differences were noted in host toxicity and in antitumor effect against tumor grown as a subcutaneous myeloblastoma. Nearly three times more neocarzinostatin was required by continuous infusion for an effect equivalent to that of bolus injection. In contrast, continuous infusion of methotrexate with concurrent thymidine infusion prevented toxicity, enhanced the antitumor effect, and prolonged survival. This infusion system should facilitate rapid preclinical evaluation of drugs considered for constant iv infusion therapy.", "contents": "Technique for preclinical evaluation of continuous infusion chemotherapy with the use of WF rat acute myelogenous leukemia. A technique was developed for continuous iv infusion chemotherapy in an inbred rat model of acute myelogenous leukemia. Polyethylene tubing was inserted surgically into the internal jugular vein of adult WF rats, burrowed sc to the base of the tail, and connected to an infusion pump. A flexible spring was sutured at the base of the tail and fastened to the cage wall; it protected the infusion catheter and allowed movement of the rat within the cage. This technique was used to compare bolus with continuous infusion therapy with adriamycin, cytosine arabinoside, and neocarzinostatin. Only small differences were noted in host toxicity and in antitumor effect against tumor grown as a subcutaneous myeloblastoma. Nearly three times more neocarzinostatin was required by continuous infusion for an effect equivalent to that of bolus injection. In contrast, continuous infusion of methotrexate with concurrent thymidine infusion prevented toxicity, enhanced the antitumor effect, and prolonged survival. This infusion system should facilitate rapid preclinical evaluation of drugs considered for constant iv infusion therapy."} {"id": "PMID:155753", "title": "Inhibition of tritiated thymidine incorporation in cultured cells by rat kidney extract.", "content": "KCl extract from rat kidney, rat liver, and Morris hepatomas inhibited [3H]thymidine incorporation into cultured cells. Tissues came from male inbred BUF rats. The most pronounced inhibition was achieved with the kidney extract. Protein synthesis was not inhibited during a 24-hour exposure of the cells to the inhibitor. Incorporation of [3H]deoxycytidine was inhibited, as was cell growth, when the kidney KCl extract was present for several days. [3H]thymidine incorporation was inhibited almost immediately after the addition of the extract. The inhibition was reversible. Regular [3H]thymidine incorporation was restored 24 hours after removal of the inhibitor, which was neither arginase nor a thymidine-degrading enzyme. The inhibitor was stable to heat (80 degrees C for 10 min) and resistant to trypsin, pronase, DNase, and RNase. Exposure of the extract to proteolytic enzymes, hyaluronidase, and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis of the treated extract. The inhibitor appeared to be a mucoprotein in which the carbohydrate moiety may be responsible for the inhibition. The KCl extract also inhibited RNA synthesis and DNA synthesis by the de novo pathway. The inhibition of phosphorylation of thymidine, however, appeared to be the primary action of the inhibitor.", "contents": "Inhibition of tritiated thymidine incorporation in cultured cells by rat kidney extract. KCl extract from rat kidney, rat liver, and Morris hepatomas inhibited [3H]thymidine incorporation into cultured cells. Tissues came from male inbred BUF rats. The most pronounced inhibition was achieved with the kidney extract. Protein synthesis was not inhibited during a 24-hour exposure of the cells to the inhibitor. Incorporation of [3H]deoxycytidine was inhibited, as was cell growth, when the kidney KCl extract was present for several days. [3H]thymidine incorporation was inhibited almost immediately after the addition of the extract. The inhibition was reversible. Regular [3H]thymidine incorporation was restored 24 hours after removal of the inhibitor, which was neither arginase nor a thymidine-degrading enzyme. The inhibitor was stable to heat (80 degrees C for 10 min) and resistant to trypsin, pronase, DNase, and RNase. Exposure of the extract to proteolytic enzymes, hyaluronidase, and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis of the treated extract. The inhibitor appeared to be a mucoprotein in which the carbohydrate moiety may be responsible for the inhibition. The KCl extract also inhibited RNA synthesis and DNA synthesis by the de novo pathway. The inhibition of phosphorylation of thymidine, however, appeared to be the primary action of the inhibitor."} {"id": "PMID:155754", "title": "[Ophthalmological opinions for liability affairs material damage (Part I) (author's transl)].", "content": "German law abides anyone reponsible for the damage he or she has caused to another person's property or corporal integrity. This includes all medical costs directed towards the restitution of health as well as economical damage in direct consequence of the corporal damage. An ophthalmological expert is to state his opinion therefore in accordance with the specific conditions of every individual case and not just according to general charts. Financial compensation is only granted for the actual results of damage inquestion. Prior damage and disability have to be remarked but not to justify a financial compensation. The question of smart-money is dealt with in Part II.", "contents": "[Ophthalmological opinions for liability affairs material damage (Part I) (author's transl)]. German law abides anyone reponsible for the damage he or she has caused to another person's property or corporal integrity. This includes all medical costs directed towards the restitution of health as well as economical damage in direct consequence of the corporal damage. An ophthalmological expert is to state his opinion therefore in accordance with the specific conditions of every individual case and not just according to general charts. Financial compensation is only granted for the actual results of damage inquestion. Prior damage and disability have to be remarked but not to justify a financial compensation. The question of smart-money is dealt with in Part II."} {"id": "PMID:155756", "title": "Bacteriological examination of a modern animal house containing small laboratory animals.", "content": "Floors and other areas totalling 1800 m2, comprising conventional and specified-pathogen-free (SPF) units, were screened bacteriologically 6 times in a year. The contamination indices observed were lower within than outside the units, and lower in the SPF than in the conventional unit. Bacterial counts in rooms containing animals in the conventional and SPF units were very similar. In all of the areas investigated within the units, most of the samples revealed less than 2 colony forming units per cm2. In contrast, high degrees of bacteriological contamination were detected in the changing rooms after showering or washing before entry. Staphylococcus epidermidis was the dominant bacterial species isolated. The bacteriological spectrum did not vary between the areas surveyed.", "contents": "Bacteriological examination of a modern animal house containing small laboratory animals. Floors and other areas totalling 1800 m2, comprising conventional and specified-pathogen-free (SPF) units, were screened bacteriologically 6 times in a year. The contamination indices observed were lower within than outside the units, and lower in the SPF than in the conventional unit. Bacterial counts in rooms containing animals in the conventional and SPF units were very similar. In all of the areas investigated within the units, most of the samples revealed less than 2 colony forming units per cm2. In contrast, high degrees of bacteriological contamination were detected in the changing rooms after showering or washing before entry. Staphylococcus epidermidis was the dominant bacterial species isolated. The bacteriological spectrum did not vary between the areas surveyed."} {"id": "PMID:155757", "title": "A review of allergic respiratory disease in laboratory animal workers.", "content": "There is increased recognition of hypersensitivity lung disease among workers with laboratory animals as an occupational disease. Symptoms of asthma in 44 of 78 workers with laboratory animal dander allergy reflected the serious consequences of this occupational ailment. Affected employee profiles induced family history of atopy; immediate (Type I) allergic reaction; symptoms of rhinitis, asthma, and cough; hypersensitivity to one or more species, most often rats, mice, and rabbits. Diagnosis depends on history and physical, radiologic, and laboratory examinations, including skin tests with relevant antigens. Control and treatment depend on environmental change (reemployment or reduction of antigen contact); mechanical devices (masks and filters); chemotherapy (bronchodilators, steroids), prophylaxis and immunotherapy (hyposensitization). Standardization of medico-legal criteria covering occupational asthma is needed.", "contents": "A review of allergic respiratory disease in laboratory animal workers. There is increased recognition of hypersensitivity lung disease among workers with laboratory animals as an occupational disease. Symptoms of asthma in 44 of 78 workers with laboratory animal dander allergy reflected the serious consequences of this occupational ailment. Affected employee profiles induced family history of atopy; immediate (Type I) allergic reaction; symptoms of rhinitis, asthma, and cough; hypersensitivity to one or more species, most often rats, mice, and rabbits. Diagnosis depends on history and physical, radiologic, and laboratory examinations, including skin tests with relevant antigens. Control and treatment depend on environmental change (reemployment or reduction of antigen contact); mechanical devices (masks and filters); chemotherapy (bronchodilators, steroids), prophylaxis and immunotherapy (hyposensitization). Standardization of medico-legal criteria covering occupational asthma is needed."} {"id": "PMID:155758", "title": "Chronic systemic Dacron and Teflon embolization of a Beall model 103 mitral valve prosthesis.", "content": "A case is presented of chronic systemic Dacron and Teflon embolism arising from a Beall Model 103 mitral valve prosthesis installed 11 years earlier. The emboli induced intense foreign body reaction resulting in numerous microgranulomas throughout the body. Multiple microinfarctions in the brain accounted for repeated episodes of transient ischemic attacks. Wearing of the prosthesis with consequent embolic complications seems to be the inevitable terminal fate of such early models of the Beall valve. Regular assessment of the functional status of such prostheses, particularly those in place for more than 5 years, is strongly recommended.", "contents": "Chronic systemic Dacron and Teflon embolization of a Beall model 103 mitral valve prosthesis. A case is presented of chronic systemic Dacron and Teflon embolism arising from a Beall Model 103 mitral valve prosthesis installed 11 years earlier. The emboli induced intense foreign body reaction resulting in numerous microgranulomas throughout the body. Multiple microinfarctions in the brain accounted for repeated episodes of transient ischemic attacks. Wearing of the prosthesis with consequent embolic complications seems to be the inevitable terminal fate of such early models of the Beall valve. Regular assessment of the functional status of such prostheses, particularly those in place for more than 5 years, is strongly recommended."} {"id": "PMID:155759", "title": "[Desmoid in a laparatomy scar].", "content": "A patient, aged 55, three years after having undergone abdominal histerectomy and adnexectomy for a myoma, developed a hard swelling near the surgical cut in the abdominal wall. A similar swelling appeared also in another patient, aged 33, as early as three months following salpingectomy for tubal pregnancy. In both cases these hard tumours radially permeating the facia and muscles were surgically removed and histologically verified as desmoids.", "contents": "[Desmoid in a laparatomy scar]. A patient, aged 55, three years after having undergone abdominal histerectomy and adnexectomy for a myoma, developed a hard swelling near the surgical cut in the abdominal wall. A similar swelling appeared also in another patient, aged 33, as early as three months following salpingectomy for tubal pregnancy. In both cases these hard tumours radially permeating the facia and muscles were surgically removed and histologically verified as desmoids."} {"id": "PMID:155760", "title": "T-cell division and aging.", "content": "The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of peak response in vitro as well as the sensitivity to stimulator cell concentration are not altered with age. Cell cycle studies demonstrate that those cells which respond in vitro to alloantigens or to concanavalin A do so with a cell cycle which does not change with the age of the lymphocyte donor. In addition, regardless of the age of the donor, those cells which divide in vitro demonstrate identical capacities to redivide. These experiments suggest that the decline in observed T-cell proliferation in mixed lymphocyte and mitogen reactivity of senescent mice is not to a decreased cell generation time or to a reduced capacity to divide and redivide but rather to a smaller population of reactive cells.", "contents": "T-cell division and aging. The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of peak response in vitro as well as the sensitivity to stimulator cell concentration are not altered with age. Cell cycle studies demonstrate that those cells which respond in vitro to alloantigens or to concanavalin A do so with a cell cycle which does not change with the age of the lymphocyte donor. In addition, regardless of the age of the donor, those cells which divide in vitro demonstrate identical capacities to redivide. These experiments suggest that the decline in observed T-cell proliferation in mixed lymphocyte and mitogen reactivity of senescent mice is not to a decreased cell generation time or to a reduced capacity to divide and redivide but rather to a smaller population of reactive cells."} {"id": "PMID:155761", "title": "An overview of immune aging.", "content": "A brief overview of the effect of age on the function of cells of the immune system is presented. Normal immune functions can begin to decline shortly after an individual reaches sexual maturity. Foremost among the cellular changes are those in the stem cells as reflected in their growth properties and the availability of precursor T cells, and in the T cell where a shift in subpopulations may be occurring. Present evidence indicates that thymic involution precedes and therefore may be responsible for the age dependent decline in the ability of the immune system to generate functional T cells. It now appears that the primary effect of thymic involution is on a T cell differentiation pathway affecting the more mature T cells first and only later the less mature T cells. Thus, the thymus may be the aging clock for the immune system. Future studies should be centered around processes regulating growth and atrophy of the thymus.", "contents": "An overview of immune aging. A brief overview of the effect of age on the function of cells of the immune system is presented. Normal immune functions can begin to decline shortly after an individual reaches sexual maturity. Foremost among the cellular changes are those in the stem cells as reflected in their growth properties and the availability of precursor T cells, and in the T cell where a shift in subpopulations may be occurring. Present evidence indicates that thymic involution precedes and therefore may be responsible for the age dependent decline in the ability of the immune system to generate functional T cells. It now appears that the primary effect of thymic involution is on a T cell differentiation pathway affecting the more mature T cells first and only later the less mature T cells. Thus, the thymus may be the aging clock for the immune system. Future studies should be centered around processes regulating growth and atrophy of the thymus."} {"id": "PMID:155762", "title": "Autoimmunity, histocompatibility, and aging.", "content": "The immunologic theory of aging proposes that the normal process of aging in man and all animals is pathogenetically related to faulty immunological processes and may be analogous to a type of autoimmune phenomena ultimately involving all body tissues. It may be said that the sharply increased incidence in elderly humans of the autoimmune and immunodeficiency \"diseases of age\" are thought to be greatly potentiated by the age-related decline in immune surveillance mechanisms particularly involving self/non-self discriminatory abilities. The major histocompatibility complex has emerged as a complex of \"supergenes\" coding for antigens whose ultimate biological function may be to serve as recognition units allowing lymphocytes to recognize self from non-self on an immunological basis. Also, recent data are consistent with our supposition that differences in age-specific peaks of various immune functional parameters in genetically homozygous mice may be influenced by genes linked to the major histocompatibility complex. These differences may account, at least in part, for the highly strain-dependent, age-specific incidence of certain diseases, including autoimmune and malignant diseases in the mouse. Heightened susceptibility to develop a particular disease in a susceptible animal occurs when a certain balance is reached between the interplay of immune functional parameters which mature, differentiate, or decline at different rates in the same animal. The age-specificity of this balance may be under partial control of H-2 or HLA-linked genes.", "contents": "Autoimmunity, histocompatibility, and aging. The immunologic theory of aging proposes that the normal process of aging in man and all animals is pathogenetically related to faulty immunological processes and may be analogous to a type of autoimmune phenomena ultimately involving all body tissues. It may be said that the sharply increased incidence in elderly humans of the autoimmune and immunodeficiency \"diseases of age\" are thought to be greatly potentiated by the age-related decline in immune surveillance mechanisms particularly involving self/non-self discriminatory abilities. The major histocompatibility complex has emerged as a complex of \"supergenes\" coding for antigens whose ultimate biological function may be to serve as recognition units allowing lymphocytes to recognize self from non-self on an immunological basis. Also, recent data are consistent with our supposition that differences in age-specific peaks of various immune functional parameters in genetically homozygous mice may be influenced by genes linked to the major histocompatibility complex. These differences may account, at least in part, for the highly strain-dependent, age-specific incidence of certain diseases, including autoimmune and malignant diseases in the mouse. Heightened susceptibility to develop a particular disease in a susceptible animal occurs when a certain balance is reached between the interplay of immune functional parameters which mature, differentiate, or decline at different rates in the same animal. The age-specificity of this balance may be under partial control of H-2 or HLA-linked genes."} {"id": "PMID:155763", "title": "Human mutations affecting aging--a review.", "content": "A review of human genetic mutations that affect aging and their potential contribution to help understand normal aging processes is presented. The lifespans of most animal species, including man, have a genetically determined maximum. The lifespan of man appears to have evolved exceedingly rapidly, which suggests that relatively few genes may determine longevity. Analysis of biochemical evolution suggests that the regulation of enzyme levels may underlie most evolutionary changes. There is a wide spectrum of human genetic mutations. Some, such as progeria and Werner's syndrome, produce a phenotype resembling premature aging and may involve genes related to the aging process. Certain human chromosomal abnormalities, such as Down's syndrome, produce an appearance of premature aging and may be due to abnormal gene regulatory mechanisms. Progress in understanding the genetic mechanisms underlying aging is likely to come from elucidation of the molecular defects that result in the premature aging syndromes and from insights gained regarding the regulatory mechanisms governing eukaryotic genetic expression.", "contents": "Human mutations affecting aging--a review. A review of human genetic mutations that affect aging and their potential contribution to help understand normal aging processes is presented. The lifespans of most animal species, including man, have a genetically determined maximum. The lifespan of man appears to have evolved exceedingly rapidly, which suggests that relatively few genes may determine longevity. Analysis of biochemical evolution suggests that the regulation of enzyme levels may underlie most evolutionary changes. There is a wide spectrum of human genetic mutations. Some, such as progeria and Werner's syndrome, produce a phenotype resembling premature aging and may involve genes related to the aging process. Certain human chromosomal abnormalities, such as Down's syndrome, produce an appearance of premature aging and may be due to abnormal gene regulatory mechanisms. Progress in understanding the genetic mechanisms underlying aging is likely to come from elucidation of the molecular defects that result in the premature aging syndromes and from insights gained regarding the regulatory mechanisms governing eukaryotic genetic expression."} {"id": "PMID:155772", "title": "Reversible translocation of antibiotic resistance determinants in Salmonella ordonez.", "content": "Salmonella ordonez (BM 2000) codes for kanamycin (Km, aphA), ampicillin (Ap), streptomycin (SmSp:aadA and Sm:aphC), chloramphenicol (Cm), tetracycline (Tc) and sulfonamide (Su) resistances and for production of colicin Ib (Cib). Genetical analysis by incompatibility testing, conjugation, transformation and physical studies using electron microscopy, agarose gel electrophoresis, led us to associate the Km and Cib characters to a 98.7 kilobase (kb) IncI1 plasmid (pIP565), and the Sm (aphC) and Su determinants to a 8.3 kb plasmid (pIP605). The ApCmSmSp(aadA)SuTc determinants were not associated in BM2000 S. ordonez with a plasmid structure. Following conjugation of S. ordonez to E. coli, the ApCmSmSpSuTc determinants were found stably associated with a single plasmid structure (pIP173, 127.5 kb) belonging to IncI1 group. Agarose gel electrophoresis of plasmid DNA restriction endonuclease digests and electron microscopy heteroduplex analysis showed that the acquisition of the ApCmSmSpSuTc determinants resulted from the insertion into pIP565 of a 28.8 kb DNA sequence. This sequence coding for ApCmSmSpSuTu resistances in S. ordonez could be translocated either to pIP565 plasmid or to several IncI1 plasmids but never to plasmids belonging to IncW, IncP or IncFII, suggesting the existence of specific sequences on the IncI1 receptor plasmids. Moreover, R-determinants were translocated back \"en bloc\" from pIP173 to the chromosome of a susceptible S. ordanez. The results were consistent with the presence in BM2000 S. ordonez chromosomal DNA of an integrated translocatable sequence encoding ApCmSmSpSuTc resistances. Such a structural association could account for the stability of these resistances in the Salmonella ordonez serotype.", "contents": "Reversible translocation of antibiotic resistance determinants in Salmonella ordonez. Salmonella ordonez (BM 2000) codes for kanamycin (Km, aphA), ampicillin (Ap), streptomycin (SmSp:aadA and Sm:aphC), chloramphenicol (Cm), tetracycline (Tc) and sulfonamide (Su) resistances and for production of colicin Ib (Cib). Genetical analysis by incompatibility testing, conjugation, transformation and physical studies using electron microscopy, agarose gel electrophoresis, led us to associate the Km and Cib characters to a 98.7 kilobase (kb) IncI1 plasmid (pIP565), and the Sm (aphC) and Su determinants to a 8.3 kb plasmid (pIP605). The ApCmSmSp(aadA)SuTc determinants were not associated in BM2000 S. ordonez with a plasmid structure. Following conjugation of S. ordonez to E. coli, the ApCmSmSpSuTc determinants were found stably associated with a single plasmid structure (pIP173, 127.5 kb) belonging to IncI1 group. Agarose gel electrophoresis of plasmid DNA restriction endonuclease digests and electron microscopy heteroduplex analysis showed that the acquisition of the ApCmSmSpSuTc determinants resulted from the insertion into pIP565 of a 28.8 kb DNA sequence. This sequence coding for ApCmSmSpSuTu resistances in S. ordonez could be translocated either to pIP565 plasmid or to several IncI1 plasmids but never to plasmids belonging to IncW, IncP or IncFII, suggesting the existence of specific sequences on the IncI1 receptor plasmids. Moreover, R-determinants were translocated back \"en bloc\" from pIP173 to the chromosome of a susceptible S. ordanez. The results were consistent with the presence in BM2000 S. ordonez chromosomal DNA of an integrated translocatable sequence encoding ApCmSmSpSuTc resistances. Such a structural association could account for the stability of these resistances in the Salmonella ordonez serotype."} {"id": "PMID:155773", "title": "Isolation and genetic analysis of nuclease halo (nuh) mutants of Neurospora crassa.", "content": "Nuclease halo (nuh) mutants of the ascomycete Neurospora crassa have been isolated which are characterized reduced release of deoxyribonuclease (DNase) activities from colonies grown on sorbose-containing agar media. To identify nuh mutants, mutagenized isolates were transferred to commercial DNase test agar, or grown on minimal medium and then overlayed with agar that contained heat-denatured DNA. DNase activity was visualized by acid precipitation which produced clear rings of digestion (haloes) around the colonies. To identify the number of genes in which mutations lead to reduced release of nuclease activity, eleven nuh mutants were checked for close linkage and linked pairs were tested for complementation. These mutants were assigned to eight genes, and all except one were mapped in six small regions of the Neurospora linkage maps. In addition, among a large number of existing mutants which were tested for nuclease haloes, two mutants were found that showed the Nuh phenotype, namely uvs-3 and uvs-6. One of the isolated nuh mutants was also found to be sensitive to UV and was mapped close to uvs-3; it may represent a new allele of this gene. As a first step towards identification of genuine nuclease mutants, extensively backcrossed strains of mutants from different genes have been assayed for nuclease activity with denatured DNA in extracts. A pronounced reduction, compared to wild type at the same stage of growth, was found in uvs-3 and also in nuh-3, a mutant that is not UV-sensitive.", "contents": "Isolation and genetic analysis of nuclease halo (nuh) mutants of Neurospora crassa. Nuclease halo (nuh) mutants of the ascomycete Neurospora crassa have been isolated which are characterized reduced release of deoxyribonuclease (DNase) activities from colonies grown on sorbose-containing agar media. To identify nuh mutants, mutagenized isolates were transferred to commercial DNase test agar, or grown on minimal medium and then overlayed with agar that contained heat-denatured DNA. DNase activity was visualized by acid precipitation which produced clear rings of digestion (haloes) around the colonies. To identify the number of genes in which mutations lead to reduced release of nuclease activity, eleven nuh mutants were checked for close linkage and linked pairs were tested for complementation. These mutants were assigned to eight genes, and all except one were mapped in six small regions of the Neurospora linkage maps. In addition, among a large number of existing mutants which were tested for nuclease haloes, two mutants were found that showed the Nuh phenotype, namely uvs-3 and uvs-6. One of the isolated nuh mutants was also found to be sensitive to UV and was mapped close to uvs-3; it may represent a new allele of this gene. As a first step towards identification of genuine nuclease mutants, extensively backcrossed strains of mutants from different genes have been assayed for nuclease activity with denatured DNA in extracts. A pronounced reduction, compared to wild type at the same stage of growth, was found in uvs-3 and also in nuh-3, a mutant that is not UV-sensitive."} {"id": "PMID:155774", "title": "Bioenergetic aspects of aerobic glucose metabolism of Escherichia coli K-12 under varying specific growth rates and glucose concentrations.", "content": "An attempt was made to find a bioenergetical explanation for the differential effect of specific growth rate and glucose concentration on glucose metabolism of Escherichia coli K-12 with the help of 2,4-dinitrophenol (DNP). The effect of DNP on biomass occurred only at high glucose concentrations. The presence of this uncoupler strongly stimulated glucose uptake rates and oxygen uptake rates, but repressed severly Yg values. Increase in glucose concentration, however, sharply decreased QO2. The amount of oxygen required for maintenance was not affected by DNP, but Yomax values were much lower in the presence of DNP. The results are discussed and it is suggested that aerobic fermentation is caused by a severe reduction of site 1 of the respiratory chain region, whereas biomass formation is affected by repression of the terminal cytochrome a2. In comparing the effect of glucose on biomass formation at similar Qglucose levels aerobic and anaerobic fermentation, repression occurred in both cases at glucose concentrations of 0.3% and above. Although the analyses of 15 enzymes established the metabolic differences, the repression of growth was common to both fermentation types.", "contents": "Bioenergetic aspects of aerobic glucose metabolism of Escherichia coli K-12 under varying specific growth rates and glucose concentrations. An attempt was made to find a bioenergetical explanation for the differential effect of specific growth rate and glucose concentration on glucose metabolism of Escherichia coli K-12 with the help of 2,4-dinitrophenol (DNP). The effect of DNP on biomass occurred only at high glucose concentrations. The presence of this uncoupler strongly stimulated glucose uptake rates and oxygen uptake rates, but repressed severly Yg values. Increase in glucose concentration, however, sharply decreased QO2. The amount of oxygen required for maintenance was not affected by DNP, but Yomax values were much lower in the presence of DNP. The results are discussed and it is suggested that aerobic fermentation is caused by a severe reduction of site 1 of the respiratory chain region, whereas biomass formation is affected by repression of the terminal cytochrome a2. In comparing the effect of glucose on biomass formation at similar Qglucose levels aerobic and anaerobic fermentation, repression occurred in both cases at glucose concentrations of 0.3% and above. Although the analyses of 15 enzymes established the metabolic differences, the repression of growth was common to both fermentation types."} {"id": "PMID:155776", "title": "[Tubal sterilization with the tupla-clip per laparoscopiam (author's transl)].", "content": "This study refers about a newly developed plastic clip which has been used with good results for the past three years in tubal sterilization. By applying this method, heat or thermal injuries are avoided and a greater possibility of refertilization is indicated. This clinical evaluation consists of experimental data of 243 women who underwent sterilization in the local OB/GYN clinics at Fulda and at Bremerhaven. 59 women were sterilized during puerperium, and 184 were sterilized irrespective of pregnancy. As complications, 2 pregnancies were observed, further 3 hematomae within the broad ligament; 11 clips dropped into the free adbominal cavity while 5 clips broke during application. After the initial difficulties, the authors of this study recommend a sterilization with this tubal clip as an alternative to the usual methods of sterilization.", "contents": "[Tubal sterilization with the tupla-clip per laparoscopiam (author's transl)]. This study refers about a newly developed plastic clip which has been used with good results for the past three years in tubal sterilization. By applying this method, heat or thermal injuries are avoided and a greater possibility of refertilization is indicated. This clinical evaluation consists of experimental data of 243 women who underwent sterilization in the local OB/GYN clinics at Fulda and at Bremerhaven. 59 women were sterilized during puerperium, and 184 were sterilized irrespective of pregnancy. As complications, 2 pregnancies were observed, further 3 hematomae within the broad ligament; 11 clips dropped into the free adbominal cavity while 5 clips broke during application. After the initial difficulties, the authors of this study recommend a sterilization with this tubal clip as an alternative to the usual methods of sterilization."} {"id": "PMID:155777", "title": "Maternal speech to normal and Down's syndrome children matched for mean length of utterance.", "content": "The study was designed to provide data on the maternal linguistic environments of normal and Down's syndrome children at three levels of language development, as assessed by children's mean length of utterances (MLU). The three MLU levels were 1.00--1.50, 1.75--2.25, and 2.50--3.00, respectively. The subjects were 21 Down's syndrome children and their natural mothers and 21 normal children and their natural mothers. Normal children ranged in chronological age from 20 to 32 months and Down's syndrome children from 3 to 12 years. A one-hour verbal interaction between mother and child was tape recorded at home in a free-play situation. Maternal speech was analyzed using 20 measures related to its output-numerical, lexical, syntactical, semantic-structural, semantic-pragmatic, and language-teaching aspects. Additionally, eight measures of children's speech related to the output-numerical, lexical, syntactical semantic-structural aspects, and to imitativeness of maternal speech were computed as a means of testing the validity of the MLU-matching that forms a basis for this study. Except for the Type-token ratio, which favored Down's syndrome children, normal and Down's syndrome children were not found to differ. In contrast, there were numerous differences between the children in the different aspects of speech considered according to language level. None of the comparisons made of mother's speech to normal and to Down's syndrome children led to differences for any of the three children's language levels studied. It appeared that the maternal linguistic environments of language-learning Down's syndrome and normal children of corresponding MLU were similar in most respects. In contrast, there were numerous differences in mother's speech according to the language level of the children addressed. This confirmed that the expressive language level of the children is a far more powerful factor in influencing maternal speech than whether they are normal or Down's syndrome children. The implications of these findings were related to the delay-difference question in the language development of Down's syndrome children and to various interpretations of the effects of maternal linguistic input for language development and for intervention programs of language enhancement in the Down's syndrome child.", "contents": "Maternal speech to normal and Down's syndrome children matched for mean length of utterance. The study was designed to provide data on the maternal linguistic environments of normal and Down's syndrome children at three levels of language development, as assessed by children's mean length of utterances (MLU). The three MLU levels were 1.00--1.50, 1.75--2.25, and 2.50--3.00, respectively. The subjects were 21 Down's syndrome children and their natural mothers and 21 normal children and their natural mothers. Normal children ranged in chronological age from 20 to 32 months and Down's syndrome children from 3 to 12 years. A one-hour verbal interaction between mother and child was tape recorded at home in a free-play situation. Maternal speech was analyzed using 20 measures related to its output-numerical, lexical, syntactical, semantic-structural, semantic-pragmatic, and language-teaching aspects. Additionally, eight measures of children's speech related to the output-numerical, lexical, syntactical semantic-structural aspects, and to imitativeness of maternal speech were computed as a means of testing the validity of the MLU-matching that forms a basis for this study. Except for the Type-token ratio, which favored Down's syndrome children, normal and Down's syndrome children were not found to differ. In contrast, there were numerous differences between the children in the different aspects of speech considered according to language level. None of the comparisons made of mother's speech to normal and to Down's syndrome children led to differences for any of the three children's language levels studied. It appeared that the maternal linguistic environments of language-learning Down's syndrome and normal children of corresponding MLU were similar in most respects. In contrast, there were numerous differences in mother's speech according to the language level of the children addressed. This confirmed that the expressive language level of the children is a far more powerful factor in influencing maternal speech than whether they are normal or Down's syndrome children. The implications of these findings were related to the delay-difference question in the language development of Down's syndrome children and to various interpretations of the effects of maternal linguistic input for language development and for intervention programs of language enhancement in the Down's syndrome child."} {"id": "PMID:155775", "title": "[Isolation of an autotrophic variant of Nocardia opaca].", "content": "A hydrogen-oxidizing autotrophic actinomycete, strain Z-766, was isolated from the neuston of a marsh near Moscow. The organism was identified as Nocardia opaca Z-766 according to its morphologo-physiological properties. The spectrum of organic compounds used by the strain, its cultural characteristics and growth are similar to those of the monotypical autotrophic microorganism N. opaca 1b described earlier. Repeated isolation of the autotrophic variant of N. opaca Z-766 suggests that the ability of this species for autotrophic growth is not a unique phenomenon. It would be expedient to construct a taxon of the subspecial range, N. opaca var. autotrophica, for autotrophic variants of N. opaca.", "contents": "[Isolation of an autotrophic variant of Nocardia opaca]. A hydrogen-oxidizing autotrophic actinomycete, strain Z-766, was isolated from the neuston of a marsh near Moscow. The organism was identified as Nocardia opaca Z-766 according to its morphologo-physiological properties. The spectrum of organic compounds used by the strain, its cultural characteristics and growth are similar to those of the monotypical autotrophic microorganism N. opaca 1b described earlier. Repeated isolation of the autotrophic variant of N. opaca Z-766 suggests that the ability of this species for autotrophic growth is not a unique phenomenon. It would be expedient to construct a taxon of the subspecial range, N. opaca var. autotrophica, for autotrophic variants of N. opaca."} {"id": "PMID:155781", "title": "Growth hormone hyperresponsiveness to dopaminergic stimulation in Huntington's chorea.", "content": "The effect of 3 dopamine (DA) mimetic drugs, i.e. bromocriptine (Bro), apomorphine (Apo) and L-3,4-Dihydroxpenylalanine (L-dopa), was evaluated on plasma growth hormone (GH) levels in 18 patients with Huntington's chorea (HC). 27 Nonobese hospitalized patients were used as controls. Mean baseline GH levels were not altered in patients with HC. Oral administration of Bro (2.5 mg po) or L-dopa (500 mg), or subcutaneous administration of Apo (1.0 mg) resulted in a significantly greater and more prompt (Bro, L-dopa) increase in plasma GH in patients than in controls. These results suggest that presence of an altered dopaminergic regulation of GH secretion in HC.", "contents": "Growth hormone hyperresponsiveness to dopaminergic stimulation in Huntington's chorea. The effect of 3 dopamine (DA) mimetic drugs, i.e. bromocriptine (Bro), apomorphine (Apo) and L-3,4-Dihydroxpenylalanine (L-dopa), was evaluated on plasma growth hormone (GH) levels in 18 patients with Huntington's chorea (HC). 27 Nonobese hospitalized patients were used as controls. Mean baseline GH levels were not altered in patients with HC. Oral administration of Bro (2.5 mg po) or L-dopa (500 mg), or subcutaneous administration of Apo (1.0 mg) resulted in a significantly greater and more prompt (Bro, L-dopa) increase in plasma GH in patients than in controls. These results suggest that presence of an altered dopaminergic regulation of GH secretion in HC."} {"id": "PMID:155783", "title": "Immune complex vasculitis, polymyositis, and hyperglobulinemic purpura.", "content": "This is the first description of a patient with both polymyositis and Waldenstr\u00f6m hyperglobulinemic purpura. There was evidence of circulating immune complexes, and immune deposits were found in dermal and muscular vessels. Similar electron-dense deposits were seen ultrastructurally in the basement membrane of both normal and abnormal microvasculature. The findings suggest that the muscle and skin lesions may be associated with deposition of circulating immune complexes in and around blood vessels, followed by complement activation and subsequent inflammation.", "contents": "Immune complex vasculitis, polymyositis, and hyperglobulinemic purpura. This is the first description of a patient with both polymyositis and Waldenstr\u00f6m hyperglobulinemic purpura. There was evidence of circulating immune complexes, and immune deposits were found in dermal and muscular vessels. Similar electron-dense deposits were seen ultrastructurally in the basement membrane of both normal and abnormal microvasculature. The findings suggest that the muscle and skin lesions may be associated with deposition of circulating immune complexes in and around blood vessels, followed by complement activation and subsequent inflammation."} {"id": "PMID:155778", "title": "Motor innervation and fiber type pattern in amyotrophic lateral sclerosis and in Charcot-Marie-Tooth disease.", "content": "A quantitive study of the terminal innervation ratio (TIR) was conducted using 18 amyotrophic lateral sclerosis (ALS) and 12 Charcot-Marie-Tooth disease (CMT) muscle biopsies. Morphometric and histochemical analyses of muscle fibers were performed in 9 ALS and 6 CMT biopsies. The results revealed that TIR and type grouping were significantly greater in CMT than in ALS. The proportion of type 3 fibers was higher in ALS, though the proportion of intermediate and type 0 fibers was significantly higher in CMT. The atrophy factor was significantly greater in type 3 than in types 1 and 2 fibers, but it was not significantly different in type 0 and intermediate fibers as compared to types 1 and 2, It appears, therefore, that CMT has a better capacity for collateral reinnervation than ALS. Type 0 and intermediate fibers may represent altered endproducts of successful collateral reinnervation.", "contents": "Motor innervation and fiber type pattern in amyotrophic lateral sclerosis and in Charcot-Marie-Tooth disease. A quantitive study of the terminal innervation ratio (TIR) was conducted using 18 amyotrophic lateral sclerosis (ALS) and 12 Charcot-Marie-Tooth disease (CMT) muscle biopsies. Morphometric and histochemical analyses of muscle fibers were performed in 9 ALS and 6 CMT biopsies. The results revealed that TIR and type grouping were significantly greater in CMT than in ALS. The proportion of type 3 fibers was higher in ALS, though the proportion of intermediate and type 0 fibers was significantly higher in CMT. The atrophy factor was significantly greater in type 3 than in types 1 and 2 fibers, but it was not significantly different in type 0 and intermediate fibers as compared to types 1 and 2, It appears, therefore, that CMT has a better capacity for collateral reinnervation than ALS. Type 0 and intermediate fibers may represent altered endproducts of successful collateral reinnervation."} {"id": "PMID:155784", "title": "Bromocriptine and dopaminergic function in Huntington disease.", "content": "The cerebrospinal fluid (CSF) content of homovanillic acid (HVA) was assayed in 10 patients with Huntington disease. On doses of less than 40 mg of bromocriptine daily, there was clinical improvement and the CSF HVA concentration increased. On higher doses of bromocriptine, chorea worsened and the CSF HVA concentration decreased. Bromocriptine at low dosage seems to act as a partial dopamine antagonist, with phenothiazine-like effects, and at higher doses it acts as a direct dopamine-receptor stimulating agent.", "contents": "Bromocriptine and dopaminergic function in Huntington disease. The cerebrospinal fluid (CSF) content of homovanillic acid (HVA) was assayed in 10 patients with Huntington disease. On doses of less than 40 mg of bromocriptine daily, there was clinical improvement and the CSF HVA concentration increased. On higher doses of bromocriptine, chorea worsened and the CSF HVA concentration decreased. Bromocriptine at low dosage seems to act as a partial dopamine antagonist, with phenothiazine-like effects, and at higher doses it acts as a direct dopamine-receptor stimulating agent."} {"id": "PMID:155789", "title": "Silicone band technique for laparoscopic tubal sterilization in the gravid and nongravid patient.", "content": "Laparoscopic tubal sterilization by the Falope ring technique was performed on 196 patients. Sixty-four patients underwent laparoscopic tubal sterilization at the time of gestation termination. One hundred thirty-two patients underwent interval laparoscopic sterilization. The complication and failure rates in the group that had both laparoscopic tubal sterilization and gestation termination was lower than in the group that had laparoscopic tubal sterilization alone. The Falope ring sterilization technique is a safe method when combined with gestation termination, and spares the patient the inconvenience and increased hazard of 2 separate procedures.", "contents": "Silicone band technique for laparoscopic tubal sterilization in the gravid and nongravid patient. Laparoscopic tubal sterilization by the Falope ring technique was performed on 196 patients. Sixty-four patients underwent laparoscopic tubal sterilization at the time of gestation termination. One hundred thirty-two patients underwent interval laparoscopic sterilization. The complication and failure rates in the group that had both laparoscopic tubal sterilization and gestation termination was lower than in the group that had laparoscopic tubal sterilization alone. The Falope ring sterilization technique is a safe method when combined with gestation termination, and spares the patient the inconvenience and increased hazard of 2 separate procedures."} {"id": "PMID:155801", "title": "Benign adenoma of the ciliary epithelium with tumour seeding.", "content": "Report on a benign epithelioma of the ciliar body which caused cataract and dislocation of the lens in a 44-year-old woman. Tumour seeding was a remarkable finding, and is a result of disruption of the epithelial lining due to active production of mucopolysaccharides by tumour cells.", "contents": "Benign adenoma of the ciliary epithelium with tumour seeding. Report on a benign epithelioma of the ciliar body which caused cataract and dislocation of the lens in a 44-year-old woman. Tumour seeding was a remarkable finding, and is a result of disruption of the epithelial lining due to active production of mucopolysaccharides by tumour cells."} {"id": "PMID:155804", "title": "Thymic deficiency in Down's syndrome.", "content": "Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells.", "contents": "Thymic deficiency in Down's syndrome. Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells."} {"id": "PMID:155805", "title": "Fungus cultures in a pediatric outpatient clinic.", "content": "Comparison of culture results with clinical impressions showed that pediatric house officers made frequent errors in diagnosing superficial fungus infections. Results of cultures on dermatophyte test medium (DTM), read by nonmycologists in the clinic, were comparably accurate with those on standard media processed in a laboratory. DTM is a useful aid in diagnosing dermatophytoses and teaching clinical mycology to pediatric residents.", "contents": "Fungus cultures in a pediatric outpatient clinic. Comparison of culture results with clinical impressions showed that pediatric house officers made frequent errors in diagnosing superficial fungus infections. Results of cultures on dermatophyte test medium (DTM), read by nonmycologists in the clinic, were comparably accurate with those on standard media processed in a laboratory. DTM is a useful aid in diagnosing dermatophytoses and teaching clinical mycology to pediatric residents."} {"id": "PMID:155807", "title": "The heart in acute glomerulonephritis: an echocardiographic study.", "content": "Patients with acute glomerulonephritis often are seen with signs suggesting heart failure. Whether these signs are due to fluid overload secondary to kidney damage only, or whether there is associated myocardial damage has not been elucidated. Fourteen children with acute glomerulonephritis were studied by echocardiography during the edematous phase of the disease and five months later to evaluate cardiac function in this disease. Left ventricular size and function remained normal in all children throughout the study. The most consistent finding was enlargement of the left atrium during the edematous phase with a return toward normal values five months later. There was no correlation between blood pressure and the echocardiographic findings. This study suggests that signs of heart failure in acute glomerulonephritis are not due to myocardial damage but probably reflect fluid overload.", "contents": "The heart in acute glomerulonephritis: an echocardiographic study. Patients with acute glomerulonephritis often are seen with signs suggesting heart failure. Whether these signs are due to fluid overload secondary to kidney damage only, or whether there is associated myocardial damage has not been elucidated. Fourteen children with acute glomerulonephritis were studied by echocardiography during the edematous phase of the disease and five months later to evaluate cardiac function in this disease. Left ventricular size and function remained normal in all children throughout the study. The most consistent finding was enlargement of the left atrium during the edematous phase with a return toward normal values five months later. There was no correlation between blood pressure and the echocardiographic findings. This study suggests that signs of heart failure in acute glomerulonephritis are not due to myocardial damage but probably reflect fluid overload."} {"id": "PMID:155809", "title": "Fluctuations in superhelical DNA.", "content": "The effect of superhelicity on the base-pair opening probability and on the probability of occurrence of cruciform states in palindromic regions is theoretically treated. The calculations show that below the superhelix density value of -sigma=0.05 superhelicity does not appreciably affect the characteristics of DNA secondary structure fluctuations. In the range of physiological superhelix densities sigma (-sigma=0.05-0.09) the base-pair opening probability markedly increases. However, within this range of sigma the base-pairs are opened only transiently and permanently open regions are not formed. Permanently opened regions appear at higher negative superhelix densities (-sigma greater than 0.10). At the values of -sigma higher than 0.06 a cruciform structure in the palindromic region centred in position 3965 proves to be the most probable fluctuational disturbance in the 0x174 duplex DNA. Different experimental approaches used for probing the fluctuations in superhelical DNA have been analysed. The results suggest that most direct quantitative information can be derived from data on the nicking of closed DNA by single strand-specific endonucleases. Such data (Wang, 1974) accord with the results of theoretical calculations. Calculations show that, due to base-pair opening, the total free energy of superhelical DNA should depend parabolically on sigma only up to some critical value of sigma=sigmac. If negative superhelicity exceeds this critical value, which under physiological conditions proves to be -sigma=0.085, the free energy should increase linearly with -sigma. The biological role of supercoiling is discussed in the light of obtained results.", "contents": "Fluctuations in superhelical DNA. The effect of superhelicity on the base-pair opening probability and on the probability of occurrence of cruciform states in palindromic regions is theoretically treated. The calculations show that below the superhelix density value of -sigma=0.05 superhelicity does not appreciably affect the characteristics of DNA secondary structure fluctuations. In the range of physiological superhelix densities sigma (-sigma=0.05-0.09) the base-pair opening probability markedly increases. However, within this range of sigma the base-pairs are opened only transiently and permanently open regions are not formed. Permanently opened regions appear at higher negative superhelix densities (-sigma greater than 0.10). At the values of -sigma higher than 0.06 a cruciform structure in the palindromic region centred in position 3965 proves to be the most probable fluctuational disturbance in the 0x174 duplex DNA. Different experimental approaches used for probing the fluctuations in superhelical DNA have been analysed. The results suggest that most direct quantitative information can be derived from data on the nicking of closed DNA by single strand-specific endonucleases. Such data (Wang, 1974) accord with the results of theoretical calculations. Calculations show that, due to base-pair opening, the total free energy of superhelical DNA should depend parabolically on sigma only up to some critical value of sigma=sigmac. If negative superhelicity exceeds this critical value, which under physiological conditions proves to be -sigma=0.085, the free energy should increase linearly with -sigma. The biological role of supercoiling is discussed in the light of obtained results."} {"id": "PMID:155813", "title": "A novel method for purification of prephenic acid.", "content": "Prephenic acid accumulated in culture filtrates of Neuro-spora crassa has been purified in 66% yield utilizing adsorption chromatography on Sephadex G-10 in the major purification steps.", "contents": "A novel method for purification of prephenic acid. Prephenic acid accumulated in culture filtrates of Neuro-spora crassa has been purified in 66% yield utilizing adsorption chromatography on Sephadex G-10 in the major purification steps."} {"id": "PMID:155814", "title": "A new method for the preparation of beta-amylase from sweet potato.", "content": "A simple method for the preparation of sweet potato beta-amylase by thymol amylose adsorption is described. The method is far more efficient and gives higher recovery of the enzyme. The crystalline enzyme thus obtained is found to be homogeneous by gel chromatography, polyacrylamide gel electrophoresis.", "contents": "A new method for the preparation of beta-amylase from sweet potato. A simple method for the preparation of sweet potato beta-amylase by thymol amylose adsorption is described. The method is far more efficient and gives higher recovery of the enzyme. The crystalline enzyme thus obtained is found to be homogeneous by gel chromatography, polyacrylamide gel electrophoresis."} {"id": "PMID:155817", "title": "Specialized transducing phage lambda carrying the genes for coupling factor of oxidative phosphorylation of Escherichia coli: increased synthesis of coupling factor on induction of prophage lambda asn.", "content": "Studies were made of the synthesis of the coupling factor complex (F1--F0) of oxidative phosphorylation after prophage induction of a set of Escherichia coli strains lysogenic for defective transducing phage lambda asn, lambda uncA, or lambda bglC. The transducing phages had been isolated from a strain of E. coli carrying prophage lambda cI857 S7 within the bglB gene located near the unc gene cluster [Miki, T., Hiraga, S., Nagata, T. & Yura, T. (1978) Proc. Natl. Acad. Sci. USA 75, 5099--5103]. When lysogenic cells carrying lambda asn and lambda cI857 S7 were induced at high temperature, synthesis of the F1-ATPase portion of the complex increased to severalfold that of the noninduced cells. In contrast, no increase was observed upon thermoinduction of cells carrying lambda uncA or lambda bglC. The number of membrane sites that could bind purified F1-ATPase also increased significantly upon induction by lambda asn but not by lambda uncA or lambda bglC. In addition, F1-depleted membranes prepared from lambda asn-induced bacteria required more dicyclohexylcarbodiimide to seal the proton pathway than did those from noninduced bacteria. These results strongly suggest that lambda asn carries a set of bacterial genes coding for all the F1 polypeptides (the alpha, beta, gamma, delta, and probably the epsilon subunits) and at least some of the genes involved in formation of F0 polypeptides. Although lambda uncA carries the structural gene (uncA) for the alpha subunit of F1-ATPase, it apparently does not carry the whole set of F1--F0 genes.", "contents": "Specialized transducing phage lambda carrying the genes for coupling factor of oxidative phosphorylation of Escherichia coli: increased synthesis of coupling factor on induction of prophage lambda asn. Studies were made of the synthesis of the coupling factor complex (F1--F0) of oxidative phosphorylation after prophage induction of a set of Escherichia coli strains lysogenic for defective transducing phage lambda asn, lambda uncA, or lambda bglC. The transducing phages had been isolated from a strain of E. coli carrying prophage lambda cI857 S7 within the bglB gene located near the unc gene cluster [Miki, T., Hiraga, S., Nagata, T. & Yura, T. (1978) Proc. Natl. Acad. Sci. USA 75, 5099--5103]. When lysogenic cells carrying lambda asn and lambda cI857 S7 were induced at high temperature, synthesis of the F1-ATPase portion of the complex increased to severalfold that of the noninduced cells. In contrast, no increase was observed upon thermoinduction of cells carrying lambda uncA or lambda bglC. The number of membrane sites that could bind purified F1-ATPase also increased significantly upon induction by lambda asn but not by lambda uncA or lambda bglC. In addition, F1-depleted membranes prepared from lambda asn-induced bacteria required more dicyclohexylcarbodiimide to seal the proton pathway than did those from noninduced bacteria. These results strongly suggest that lambda asn carries a set of bacterial genes coding for all the F1 polypeptides (the alpha, beta, gamma, delta, and probably the epsilon subunits) and at least some of the genes involved in formation of F0 polypeptides. Although lambda uncA carries the structural gene (uncA) for the alpha subunit of F1-ATPase, it apparently does not carry the whole set of F1--F0 genes."} {"id": "PMID:155818", "title": "In vitro synthesis of the Ca2+ transport ATPase by ribosomes bound to sarcoplasmic reticulum membranes.", "content": "The calcium transport ATPase (M(r) 100,000) from sarcoplasmic reticulum membranes was synthesized in a cell-free translation system containing rough microsomes or detergent-treated bound polysomes from 14- to 16-day old chicken embryo muscles. Immunoprecipitates obtained from total translation mixtures treated with anti-ATPase antiserum contained 1.5% of the total radioactivity incorporated in vitro. A polypeptide with the electrophoretic mobility, isoelectric point, and [(35)S]methionine-labeled tryptic peptide pattern of the mature ATPase was a major component of these immunoprecipitates. By contrast, free polysomes from the same source, which were capable of high levels of in vitro protein synthesis, did not yield immunoprecipitable ATPase. ATPase synthesized in rough microsomes was not released by treatment with 10 mM EDTA in a high-salt medium (0.5 M KCl) which removes ribosomes and peripheral membrane proteins. Furthermore, labeled ATPase remained associated with the microsomes after these were treated with low concentrations of deoxycholate (0.1 mg/mg of protein in 0.3 ml) which release the luminal content of the vesicles. Only with higher deoxycholate concentrations (0.5 mg/mg of protein in 0.3 ml), which cause membrane dissolution, was the labeled ATPase found on the detergent extracts. These observations indicate that newly synthesized ATPase discharged from bound ribosomes is transferred directly to the sarcoplasmic reticulum membranes where it is incorporated as an integral membrane protein.", "contents": "In vitro synthesis of the Ca2+ transport ATPase by ribosomes bound to sarcoplasmic reticulum membranes. The calcium transport ATPase (M(r) 100,000) from sarcoplasmic reticulum membranes was synthesized in a cell-free translation system containing rough microsomes or detergent-treated bound polysomes from 14- to 16-day old chicken embryo muscles. Immunoprecipitates obtained from total translation mixtures treated with anti-ATPase antiserum contained 1.5% of the total radioactivity incorporated in vitro. A polypeptide with the electrophoretic mobility, isoelectric point, and [(35)S]methionine-labeled tryptic peptide pattern of the mature ATPase was a major component of these immunoprecipitates. By contrast, free polysomes from the same source, which were capable of high levels of in vitro protein synthesis, did not yield immunoprecipitable ATPase. ATPase synthesized in rough microsomes was not released by treatment with 10 mM EDTA in a high-salt medium (0.5 M KCl) which removes ribosomes and peripheral membrane proteins. Furthermore, labeled ATPase remained associated with the microsomes after these were treated with low concentrations of deoxycholate (0.1 mg/mg of protein in 0.3 ml) which release the luminal content of the vesicles. Only with higher deoxycholate concentrations (0.5 mg/mg of protein in 0.3 ml), which cause membrane dissolution, was the labeled ATPase found on the detergent extracts. These observations indicate that newly synthesized ATPase discharged from bound ribosomes is transferred directly to the sarcoplasmic reticulum membranes where it is incorporated as an integral membrane protein."} {"id": "PMID:155819", "title": "Presence of heparan sulfate in the glomerular basement membrane.", "content": "The glomerular basement membrane was subjected to digestion with specific enzymes to determine the chemical nature (sialoglycoproteins, collagenous peptides, or glycosaminoglycans) of the anionic sites previously demonstrated in the laminae rarae. Enzyme digestion was carried out both in situ and in vitro. Kidneys were perfused in situ with enzyme solutions followed by perfusion with fixative containing the cationic dye, ruthenium red, to detect the anionic sites. Glomerular basement membranes were isolated by detergent treatment of glomeruli and incubated with enzyme solutions, followed by incubation with cationized ferritin (pI 7.3-7.5) to label the anionic sites. Only highly purified enzymes free of proteolytic activity were used. The findings were the same both in situ and in vitro. The anionic sites were unaffected by treatment with neuraminidase, chondroitinase ABC, and testicular or leech hyaluronidase. However, they could no longer be demonstrated after digestion with crude heparinase, purified heparitinase, or Pronase or after nitrous acid oxidation. The results demonstrate that the sites contain heparan sulfate since they are removed by treatment with heparitinase and by nitrous acid oxidation-procedures specific for heparan sulfate; and that sialoglycoproteins or other glycosaminoglycans do not represent major components of these sites since the latter are not affected by digestion with neuraminidase and other glycosaminoglycan-specific enzymes. Identical findings were obtained on basement membranes in other locations (Bowman's capsule, tubule epithelium, and endothelium of peritubular capillaries). The presence of heparan sulfate in the glomerular basement membrane is discussed in relation to the charge-selective properties of the glomerular filter and in relation to its potential involvement in various types of glomerular injury.", "contents": "Presence of heparan sulfate in the glomerular basement membrane. The glomerular basement membrane was subjected to digestion with specific enzymes to determine the chemical nature (sialoglycoproteins, collagenous peptides, or glycosaminoglycans) of the anionic sites previously demonstrated in the laminae rarae. Enzyme digestion was carried out both in situ and in vitro. Kidneys were perfused in situ with enzyme solutions followed by perfusion with fixative containing the cationic dye, ruthenium red, to detect the anionic sites. Glomerular basement membranes were isolated by detergent treatment of glomeruli and incubated with enzyme solutions, followed by incubation with cationized ferritin (pI 7.3-7.5) to label the anionic sites. Only highly purified enzymes free of proteolytic activity were used. The findings were the same both in situ and in vitro. The anionic sites were unaffected by treatment with neuraminidase, chondroitinase ABC, and testicular or leech hyaluronidase. However, they could no longer be demonstrated after digestion with crude heparinase, purified heparitinase, or Pronase or after nitrous acid oxidation. The results demonstrate that the sites contain heparan sulfate since they are removed by treatment with heparitinase and by nitrous acid oxidation-procedures specific for heparan sulfate; and that sialoglycoproteins or other glycosaminoglycans do not represent major components of these sites since the latter are not affected by digestion with neuraminidase and other glycosaminoglycan-specific enzymes. Identical findings were obtained on basement membranes in other locations (Bowman's capsule, tubule epithelium, and endothelium of peritubular capillaries). The presence of heparan sulfate in the glomerular basement membrane is discussed in relation to the charge-selective properties of the glomerular filter and in relation to its potential involvement in various types of glomerular injury."} {"id": "PMID:155820", "title": "Possible involvement of serotonin in extinction.", "content": "In Experiment 1, rats were trained to leverpress for continuous reinforcement with food; half were then intubated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA: 400 mg/kg) and half with water. In extinction the PCPA-treated rats responded at a higher rate. In Experiment 2, rats were trained on a random interval schedule and then assigned to two groups, treated as in Experiment 1, and tested in extinction. There was no significant difference in the resistance to extinction of the two groups. In Experiment 3, the responding of rats trained in a punished stepdown response paradigm and then given an intragastric injection of PCPA took longer to recover than the responding of water-injected controls. These observations suggest that serotonergic neurons might play a role in extinction processes.", "contents": "Possible involvement of serotonin in extinction. In Experiment 1, rats were trained to leverpress for continuous reinforcement with food; half were then intubated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA: 400 mg/kg) and half with water. In extinction the PCPA-treated rats responded at a higher rate. In Experiment 2, rats were trained on a random interval schedule and then assigned to two groups, treated as in Experiment 1, and tested in extinction. There was no significant difference in the resistance to extinction of the two groups. In Experiment 3, the responding of rats trained in a punished stepdown response paradigm and then given an intragastric injection of PCPA took longer to recover than the responding of water-injected controls. These observations suggest that serotonergic neurons might play a role in extinction processes."} {"id": "PMID:155825", "title": "Reticulospinal neurones with axons in the dorsal part of the lateral funiculus of the lumbar segments.", "content": "The presence of reticulospinal axons in the dorsal part of the lateral funiculus (DLF) of the lumbar spinal cord segments was tested in chloralose-anaesthetized cats. In the medial part of the reticular formation, 59 units which gave antidromic responses to stimulation of the isolated DLF of segment L1--L3 were observed. The rate of their axonal conduction was 20--120 m/s. 62% of the units generated discharge activity in response to electrical stimulation of the skin of the trunk and/or the limbs. The activating intraspinal pathways were localized in the DLF and the ventral part of the cord. The most effective natural stimulus was tapping. Monosynaptic control from cerebellar pathways was confirmed in 37% of reticulospinal neurones with axones in the DLF. The results showed that reticulospinal axones form part of the dorsal reticulospinal system in the lumbar cord region.", "contents": "Reticulospinal neurones with axons in the dorsal part of the lateral funiculus of the lumbar segments. The presence of reticulospinal axons in the dorsal part of the lateral funiculus (DLF) of the lumbar spinal cord segments was tested in chloralose-anaesthetized cats. In the medial part of the reticular formation, 59 units which gave antidromic responses to stimulation of the isolated DLF of segment L1--L3 were observed. The rate of their axonal conduction was 20--120 m/s. 62% of the units generated discharge activity in response to electrical stimulation of the skin of the trunk and/or the limbs. The activating intraspinal pathways were localized in the DLF and the ventral part of the cord. The most effective natural stimulus was tapping. Monosynaptic control from cerebellar pathways was confirmed in 37% of reticulospinal neurones with axones in the DLF. The results showed that reticulospinal axones form part of the dorsal reticulospinal system in the lumbar cord region."} {"id": "PMID:155826", "title": "Study of electrical activity in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a high protein and high fat diet.", "content": "The authors studied bioelectric potentials in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a standard, a high protein and a high fat diet. On the first 3--6 days after changing from the standard to the high fat and high protein diets, a decrease in the amplitude of electrical activity was recorded in both the areas in question. It was also found that the frequency of electrical activity in the hypothalamic ventromedial nucleus or the lateral hypothalamus rose, after 3 days administration of the high fat or the high protein diet, in correlation to the type of diet, and that, in the frequency spectrum, a change occurred in the proportion of basic frequency in relation to superimposed frequencies distorting it. It was further found that there was a permanent difference between the amplitude of electrical activity in the lateral hypothalamus and the hypothalamic ventromedial nucleus.", "contents": "Study of electrical activity in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a high protein and high fat diet. The authors studied bioelectric potentials in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a standard, a high protein and a high fat diet. On the first 3--6 days after changing from the standard to the high fat and high protein diets, a decrease in the amplitude of electrical activity was recorded in both the areas in question. It was also found that the frequency of electrical activity in the hypothalamic ventromedial nucleus or the lateral hypothalamus rose, after 3 days administration of the high fat or the high protein diet, in correlation to the type of diet, and that, in the frequency spectrum, a change occurred in the proportion of basic frequency in relation to superimposed frequencies distorting it. It was further found that there was a permanent difference between the amplitude of electrical activity in the lateral hypothalamus and the hypothalamic ventromedial nucleus."} {"id": "PMID:155827", "title": "Theta (RSA) activity in the brain of the turtle.", "content": "The existence of a synchronizing system generating theta (RSA) activity of an average frequency of 4 Hz has been demonstrated in the brain of the turtle Testudo Graeca. Three brain structures probably participate in the activity--the septum, amygdala and hippocampus. The septal region seems to play a leading role in this complex--lesions in this region abolished the generation of theta activity in 71% of experiments. This synchronizing system is functionally coupled with the olfactory generator of electrographic respiratory response (ERR), which is brought into activity by nasal air flow. This coupling can play a role in genesis of epileptic electrographic activities not only in the turtle, but also in phylogenetically higher species.", "contents": "Theta (RSA) activity in the brain of the turtle. The existence of a synchronizing system generating theta (RSA) activity of an average frequency of 4 Hz has been demonstrated in the brain of the turtle Testudo Graeca. Three brain structures probably participate in the activity--the septum, amygdala and hippocampus. The septal region seems to play a leading role in this complex--lesions in this region abolished the generation of theta activity in 71% of experiments. This synchronizing system is functionally coupled with the olfactory generator of electrographic respiratory response (ERR), which is brought into activity by nasal air flow. This coupling can play a role in genesis of epileptic electrographic activities not only in the turtle, but also in phylogenetically higher species."} {"id": "PMID:155828", "title": "In vivo kinetics of blood cholinesterase inhibition by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine in rats.", "content": "In vivo inhibition of blood acetylcholinesterase activity by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine was studied in rats. Changes of enzyme activity in the blood were continually registered using an automatic colorimeter Auto Analyzer system. The dependence of % enzyme inhibition upon time in semilogarithmic transformation was characterized by a two phase curve. The first phase reflected the increase in the concentration of inhibitors in the blood during their resorption; this was followed by a slow second phase of inhibition. The inhibitory effect decreased in the order: physostigmine greater than tacrine greater than 7-methoxytacrine. The relationship between the anticholinesterase and antipsychotomimetic action of the examined substances is discussed.", "contents": "In vivo kinetics of blood cholinesterase inhibition by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine in rats. In vivo inhibition of blood acetylcholinesterase activity by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine was studied in rats. Changes of enzyme activity in the blood were continually registered using an automatic colorimeter Auto Analyzer system. The dependence of % enzyme inhibition upon time in semilogarithmic transformation was characterized by a two phase curve. The first phase reflected the increase in the concentration of inhibitors in the blood during their resorption; this was followed by a slow second phase of inhibition. The inhibitory effect decreased in the order: physostigmine greater than tacrine greater than 7-methoxytacrine. The relationship between the anticholinesterase and antipsychotomimetic action of the examined substances is discussed."} {"id": "PMID:155831", "title": "Physical fitness of Czechoslovak population between the ages of 12 and 55 years. Pulse rate and blood pressure.", "content": "In loading test of a representative sample of the Czechoslovak population aged 12--55 years, the authors, examined the reaction of the pulse rate and blood pressure (in watts--W) to loading on a bicycle ergometer. On increasing the submaximal load, the pulse rate rose linearly with age--more gradually in the phase of growth and along an approximately the same trend from the age of 18. The course in adult women corresponded to the course in boys aged about 13. The maximum pulse rate fell linearly in correlation to age, by about 4--5 beats for every 10 years, from 195/min in 12-year-old boys and 198/min in girls. The working capacity at pulse rate 170 (W 170) attained the maximum at 25 years (men 198, women 112 W). The systolic pressure rose non-linearly with loading. It increased more rapidly at lower loads. Children had the smallest pressure reaction and the oldest subjects the greatest. Diastolic pressure fell gradually and non-linearly with loading. The maximum blood pressure values, according to age, rose from 138/56 torr in the oldest males and from 139/57 to 182/84 torr in females.", "contents": "Physical fitness of Czechoslovak population between the ages of 12 and 55 years. Pulse rate and blood pressure. In loading test of a representative sample of the Czechoslovak population aged 12--55 years, the authors, examined the reaction of the pulse rate and blood pressure (in watts--W) to loading on a bicycle ergometer. On increasing the submaximal load, the pulse rate rose linearly with age--more gradually in the phase of growth and along an approximately the same trend from the age of 18. The course in adult women corresponded to the course in boys aged about 13. The maximum pulse rate fell linearly in correlation to age, by about 4--5 beats for every 10 years, from 195/min in 12-year-old boys and 198/min in girls. The working capacity at pulse rate 170 (W 170) attained the maximum at 25 years (men 198, women 112 W). The systolic pressure rose non-linearly with loading. It increased more rapidly at lower loads. Children had the smallest pressure reaction and the oldest subjects the greatest. Diastolic pressure fell gradually and non-linearly with loading. The maximum blood pressure values, according to age, rose from 138/56 torr in the oldest males and from 139/57 to 182/84 torr in females."} {"id": "PMID:155832", "title": "Physical fitness of the Czechoslovak population between the ages of 12 and 55 years. Pulmonary ventilation.", "content": "Examination of ventilation function in an average population showed that maximum minute ventilation in adults fell with advancing age. Males had higher values than females, the highest values being attained, in both sexes, at 18 (117 and 83 1/min respectively). Tidal volume during loading, expressed as a percentage of vital capacity, rose with advancing age in all groups of males and females (from 53% at 18 to 64% at 55 in males and from 51% to 59% in females). The ventilation equivalents for O2 and CO2 attained optimum values at a load of 100 W in males and at 50 W in females. On increasing the load they rose in both sexes--in females more than in males. Percentual utilization of O2 from the inspired air was greatest in males at a load of about 100 W (4.8--5%) and in females at about 50 W (4.3--4.8%). At higher loads it fell faster in females than in males. In males, the respiratory quocient attained the value 1 at a load of about 2 W/kg body weight and in females at 1.5 W/kg. At maximum loading it was over 1 in all the age categories. No differences between males and females were observed, but males, in maximum loading, gave the greatest absolute and the greatest relative performance.", "contents": "Physical fitness of the Czechoslovak population between the ages of 12 and 55 years. Pulmonary ventilation. Examination of ventilation function in an average population showed that maximum minute ventilation in adults fell with advancing age. Males had higher values than females, the highest values being attained, in both sexes, at 18 (117 and 83 1/min respectively). Tidal volume during loading, expressed as a percentage of vital capacity, rose with advancing age in all groups of males and females (from 53% at 18 to 64% at 55 in males and from 51% to 59% in females). The ventilation equivalents for O2 and CO2 attained optimum values at a load of 100 W in males and at 50 W in females. On increasing the load they rose in both sexes--in females more than in males. Percentual utilization of O2 from the inspired air was greatest in males at a load of about 100 W (4.8--5%) and in females at about 50 W (4.3--4.8%). At higher loads it fell faster in females than in males. In males, the respiratory quocient attained the value 1 at a load of about 2 W/kg body weight and in females at 1.5 W/kg. At maximum loading it was over 1 in all the age categories. No differences between males and females were observed, but males, in maximum loading, gave the greatest absolute and the greatest relative performance."} {"id": "PMID:155833", "title": "Physical fitness of the Czechoslovak population between the ages of 12 and 55 years. Oxygen consumption and pulse oxygen.", "content": "The authors measured oxygen consumption in a Czechoslovak population aged from 12 to 55 years. An abrupt increase was found between 12 and 18 years, when the maximum was reached (males 3.28, females 2.17 l/min), followed by a slower decrease to 55 years. Relative O2 consumption (per kg body weight) showed a continuous decrease from 12 years, when maximum values were recorded (49 ml/min . kg for boys, 46 ml/min . kg for girls), to 55 (33 ml/min . kg for males, 27 ml/min . kg for females). In the adult population (18--55 years), no differences were observed in the values at the various levels of submaximal loading. The pulse oxygen attained the maximum at 18 (males 16.8, females 11 ml).", "contents": "Physical fitness of the Czechoslovak population between the ages of 12 and 55 years. Oxygen consumption and pulse oxygen. The authors measured oxygen consumption in a Czechoslovak population aged from 12 to 55 years. An abrupt increase was found between 12 and 18 years, when the maximum was reached (males 3.28, females 2.17 l/min), followed by a slower decrease to 55 years. Relative O2 consumption (per kg body weight) showed a continuous decrease from 12 years, when maximum values were recorded (49 ml/min . kg for boys, 46 ml/min . kg for girls), to 55 (33 ml/min . kg for males, 27 ml/min . kg for females). In the adult population (18--55 years), no differences were observed in the values at the various levels of submaximal loading. The pulse oxygen attained the maximum at 18 (males 16.8, females 11 ml)."} {"id": "PMID:155834", "title": "Cultivation of frozen mouse bone marrow cells in agar.", "content": "The authors attempted to cultivate frozen mouse bone marrow cells in a semisolid medium. They demonstrated that the stem haematopoietic cells of frozen mouse bone marrow were capable of proliferation and of colony formation on agar. The much smaller number of colonies from frozen mouse bone marrow (about 80% fewer) compared with fresh marrow is evidence that part of the stem haematopoietic cell population retains proliferative capacity even after freezing.", "contents": "Cultivation of frozen mouse bone marrow cells in agar. The authors attempted to cultivate frozen mouse bone marrow cells in a semisolid medium. They demonstrated that the stem haematopoietic cells of frozen mouse bone marrow were capable of proliferation and of colony formation on agar. The much smaller number of colonies from frozen mouse bone marrow (about 80% fewer) compared with fresh marrow is evidence that part of the stem haematopoietic cell population retains proliferative capacity even after freezing."} {"id": "PMID:155837", "title": "Experiences with the tensor fascia lata flap.", "content": "Our experience with 60 TFL flaps is reviewed. The anatomy and the arcs of rotation of this flap are described. Our clinical experience--particularly in reconstruction of the groin and abdominal wall, and in free flap transfers--has been detailed, including the use of a free osteomyocutaneous sensory TFL flap for reconstruction of the heel.", "contents": "Experiences with the tensor fascia lata flap. Our experience with 60 TFL flaps is reviewed. The anatomy and the arcs of rotation of this flap are described. Our clinical experience--particularly in reconstruction of the groin and abdominal wall, and in free flap transfers--has been detailed, including the use of a free osteomyocutaneous sensory TFL flap for reconstruction of the heel."} {"id": "PMID:155838", "title": "The effect of dopamine and noradrenaline blockade on amphetamine-induced behaviour in the marmoset.", "content": "Acute administration of 4 mg/kg d-amphetamine in the marmoset results in a large increase in small head movements (checking), an almost total suppression of purposeful activities and social interaction, but little change in the amount of locomotion. Checking behaviour is blocked in a dose dependent manner by 0.03--0.18 mg/kg haloperidol but not by propranolol, aceperone or diazepam, suggesting dopaminergic mediation of this behaviour. The loss of activities and social interaction after amphetamine is not antagonized by any of the drugs used in this study. Locomotion is decreased by haloperidol, propranolol and diazepam in amphetamine treated animals and by haloperidol and aceperone in normal animals.", "contents": "The effect of dopamine and noradrenaline blockade on amphetamine-induced behaviour in the marmoset. Acute administration of 4 mg/kg d-amphetamine in the marmoset results in a large increase in small head movements (checking), an almost total suppression of purposeful activities and social interaction, but little change in the amount of locomotion. Checking behaviour is blocked in a dose dependent manner by 0.03--0.18 mg/kg haloperidol but not by propranolol, aceperone or diazepam, suggesting dopaminergic mediation of this behaviour. The loss of activities and social interaction after amphetamine is not antagonized by any of the drugs used in this study. Locomotion is decreased by haloperidol, propranolol and diazepam in amphetamine treated animals and by haloperidol and aceperone in normal animals."} {"id": "PMID:155854", "title": "[The patello-femoral joint in osteoarthritis of the knee with gene varum (author's transl)].", "content": "The authors have treated 63 knees with osteoarthritis associated with varus deformity by valgus osteotomies. The clinical and radiological state of the patello-femoral joints has been studied before and after correction of varus deformity. No correlation was found between the severity of tibio-femoral osteoarthritis and patello-femoral osteoarthritis. Medical patello-femoral discordance was found in 12 p. 100 of the cases. Clinical evidence of pain arising from the patello-femoral joint was more often found than evidence of radiological abnormality. It is concluded that pain arising from the medial compartment may be confused with patello-femoral pain. A five-year follow-up showed that the patello-femoral joint was not influenced radiologically by the valgus osteotomy but patellar pain was improved in most of the cases. Procedures to re-align the patella should not normally be associated with valgus osteotomy in cases in which patellar pain exists in association with osteoarthritis of the knee with varus deformity.", "contents": "[The patello-femoral joint in osteoarthritis of the knee with gene varum (author's transl)]. The authors have treated 63 knees with osteoarthritis associated with varus deformity by valgus osteotomies. The clinical and radiological state of the patello-femoral joints has been studied before and after correction of varus deformity. No correlation was found between the severity of tibio-femoral osteoarthritis and patello-femoral osteoarthritis. Medical patello-femoral discordance was found in 12 p. 100 of the cases. Clinical evidence of pain arising from the patello-femoral joint was more often found than evidence of radiological abnormality. It is concluded that pain arising from the medial compartment may be confused with patello-femoral pain. A five-year follow-up showed that the patello-femoral joint was not influenced radiologically by the valgus osteotomy but patellar pain was improved in most of the cases. Procedures to re-align the patella should not normally be associated with valgus osteotomy in cases in which patellar pain exists in association with osteoarthritis of the knee with varus deformity."} {"id": "PMID:155859", "title": "[Ununited fractures of the femoral neck treated by cervicocephalic impaction. A report of two cases (author's transl)].", "content": "Two cases of ununited fracture of the femoral neck, treated by a technique described by Brackett (1927) and modified by Merle d'Aubign\u00e9 (1968) are reported. The femoral head was partly evacuated, care being taken to preserve its blood supply and then impacted onto the femoral neck. The results were found to be satisfactory.", "contents": "[Ununited fractures of the femoral neck treated by cervicocephalic impaction. A report of two cases (author's transl)]. Two cases of ununited fracture of the femoral neck, treated by a technique described by Brackett (1927) and modified by Merle d'Aubign\u00e9 (1968) are reported. The femoral head was partly evacuated, care being taken to preserve its blood supply and then impacted onto the femoral neck. The results were found to be satisfactory."} {"id": "PMID:155867", "title": "Characterization of the decreased ATPase activity of rat cardiac actomyosin in isoproterenol-induced cardiac hypertrophy.", "content": "Daily administration of d,l isoproterenol-HCl (5 mg/kg) in rats for periods of 14-21 days results in marked cardiac hypertrophy and a decrease in cardiac actomyosin ATPase activity. Actomyosin suspensions (ionic strength 0.08) from right and left ventricles showed average decreases in ATPase activity of 37.1% (p less than 0.005) and 35.7% (p less than 0.05), respectively, for animals treated with isoproterenol for 14 days. Isolated myofibrils from combined ventricular muscle of another group of animals that received the same isoproterenol treatment showed an average decrease in ATPase of 36.4% (p less than 0.0025). The later experiments also demonstrated that the decrease in ATPase activity was not Ca++ sensitive suggesting the lack of involvement of a change in the calcium regulatory factors (tropomyosin-troponin complex). In contrast to these findings, purified myosin from treated animals and actomyosin assayed under conditions which essentially reflect myosin ATPase activity uninfluenced by actin interaction (actomyosin in solution, ionic strength 0.6), did not demonstrate a change in ATPase from controls. It was concluded that the decrease in cardiac actomyosin ATPase in isoproterenol treated rats involved primarily a defect in actin or the interaction of actin with other components of the contractile protein complex.", "contents": "Characterization of the decreased ATPase activity of rat cardiac actomyosin in isoproterenol-induced cardiac hypertrophy. Daily administration of d,l isoproterenol-HCl (5 mg/kg) in rats for periods of 14-21 days results in marked cardiac hypertrophy and a decrease in cardiac actomyosin ATPase activity. Actomyosin suspensions (ionic strength 0.08) from right and left ventricles showed average decreases in ATPase activity of 37.1% (p less than 0.005) and 35.7% (p less than 0.05), respectively, for animals treated with isoproterenol for 14 days. Isolated myofibrils from combined ventricular muscle of another group of animals that received the same isoproterenol treatment showed an average decrease in ATPase of 36.4% (p less than 0.0025). The later experiments also demonstrated that the decrease in ATPase activity was not Ca++ sensitive suggesting the lack of involvement of a change in the calcium regulatory factors (tropomyosin-troponin complex). In contrast to these findings, purified myosin from treated animals and actomyosin assayed under conditions which essentially reflect myosin ATPase activity uninfluenced by actin interaction (actomyosin in solution, ionic strength 0.6), did not demonstrate a change in ATPase from controls. It was concluded that the decrease in cardiac actomyosin ATPase in isoproterenol treated rats involved primarily a defect in actin or the interaction of actin with other components of the contractile protein complex."} {"id": "PMID:155872", "title": "[Atypical findings in lumbar discography (author's transl)].", "content": "Lumbar discography is a good supplement to myelography in the evaluation of low back pain and sciatica. Knowledge of both typical and atypical findings helps to avoid false positive and negative diagnoses. On the other hand atypical findings may show up pathological processes, elsewhere only seen by pathological anatomy. In some cases a relation between these phenomena and clinical symptoms is found.", "contents": "[Atypical findings in lumbar discography (author's transl)]. Lumbar discography is a good supplement to myelography in the evaluation of low back pain and sciatica. Knowledge of both typical and atypical findings helps to avoid false positive and negative diagnoses. On the other hand atypical findings may show up pathological processes, elsewhere only seen by pathological anatomy. In some cases a relation between these phenomena and clinical symptoms is found."} {"id": "PMID:155874", "title": "Intrahepatic pressures measured during laparoscopy.", "content": "Intrahepatic pressure measured during laparoscopy were all correlated to occluded hepatic vein pressures and thereby to the portal vein pressures. Assessment of the intrahepatic pressures increases the diagnostic yield of laparoscopy, and should be used whenever it is important to quantitate the pressure in the portal circulation.", "contents": "Intrahepatic pressures measured during laparoscopy. Intrahepatic pressure measured during laparoscopy were all correlated to occluded hepatic vein pressures and thereby to the portal vein pressures. Assessment of the intrahepatic pressures increases the diagnostic yield of laparoscopy, and should be used whenever it is important to quantitate the pressure in the portal circulation."} {"id": "PMID:155875", "title": "Functional characterization in vitro of two human T-cell subpopulations with different affinities to sheep erythrocytes.", "content": "On the basis of their different abilities to form resettes with unsensitized sheep erythrocytes (SRBC), two subpopulations of human T lymphocytes were separated by the rosette sedimentation technique. In a series of in vitro experiments the T cells carrying high-avidity receptors for SRBC ('active' T cells) were shown to respond significantly better when stimulated with purified protein derivative (PPD) and allogeneic cells than the subpopulation carrying low-avidity receptors ('non-active' T cells). On the other hand, the latter responded better to phytohaemagglutinin, concanavalin A and pokeweed mitogen; it was likewise demonstrated that these cells were better stimulators in a mixed lymphocyte reaction. The role of monocytes in mitogen and PPD responses was investigated by adding such cells to Fe-treated suspensions. These were found to be crucial for an optimal response of both subpopulations. Furthermore, different patterns of activation were observed for the active and non-active cells. Especially interesting was the observation that the Con A response of the active fraction was more monocyte-dependent than that of the non-active one.", "contents": "Functional characterization in vitro of two human T-cell subpopulations with different affinities to sheep erythrocytes. On the basis of their different abilities to form resettes with unsensitized sheep erythrocytes (SRBC), two subpopulations of human T lymphocytes were separated by the rosette sedimentation technique. In a series of in vitro experiments the T cells carrying high-avidity receptors for SRBC ('active' T cells) were shown to respond significantly better when stimulated with purified protein derivative (PPD) and allogeneic cells than the subpopulation carrying low-avidity receptors ('non-active' T cells). On the other hand, the latter responded better to phytohaemagglutinin, concanavalin A and pokeweed mitogen; it was likewise demonstrated that these cells were better stimulators in a mixed lymphocyte reaction. The role of monocytes in mitogen and PPD responses was investigated by adding such cells to Fe-treated suspensions. These were found to be crucial for an optimal response of both subpopulations. Furthermore, different patterns of activation were observed for the active and non-active cells. Especially interesting was the observation that the Con A response of the active fraction was more monocyte-dependent than that of the non-active one."} {"id": "PMID:155876", "title": "Cytotoxic effects of activated human monocytes and lymphocytes to anti-D-treated human erythrocytes in vitro.", "content": "Incubation of human monocytes, derived from peripheral blood, with cell-free supernatants from mixed lymphocyte cultures resulted in morphological and functional changes in the mature macrophages. Activation of monocyte-derived macrophages by these factors resulted in a significant increase in their capacity to lyse anti-D-treated human erythrocytes. The lytic activity of both normal and activated macrophages appeared to be independent of erythrophagocytosis. T lymphocytes activated by either allogeneic cells or the mitogen phytohaemagglutinin were not cytolytic to treated erythrocytes even at high effector to target cell ratios.", "contents": "Cytotoxic effects of activated human monocytes and lymphocytes to anti-D-treated human erythrocytes in vitro. Incubation of human monocytes, derived from peripheral blood, with cell-free supernatants from mixed lymphocyte cultures resulted in morphological and functional changes in the mature macrophages. Activation of monocyte-derived macrophages by these factors resulted in a significant increase in their capacity to lyse anti-D-treated human erythrocytes. The lytic activity of both normal and activated macrophages appeared to be independent of erythrophagocytosis. T lymphocytes activated by either allogeneic cells or the mitogen phytohaemagglutinin were not cytolytic to treated erythrocytes even at high effector to target cell ratios."} {"id": "PMID:155877", "title": "[Diminished peritoneal pain perception in patients with liver cirrhosis and ascites].", "content": "Complete loss of parietal peritoneal sensitivity observed in a patient with long-standing ascites secondary to cirrhosis of the liver prompted an investigation of peritoneal sensitivity in 22 patients with the same condition. In all of them a decrease of the peritoneal sensitivity to needle perforation was found. All perceived peritoneal perforation as less painful than perforation of the abdominal skin by the same needle. In 8 control patients perforation of the peritoneum caused more discomfort than the perforation of the skin. In 7 cirrhotic patients where a histologic examination of the parietal peritoneum was available a chronic fibrotic peritonitis was present. Peritoneal insensitivity may partly account for mild abdominal symptoms in cirrhotics developing bacterial peritonitis.", "contents": "[Diminished peritoneal pain perception in patients with liver cirrhosis and ascites]. Complete loss of parietal peritoneal sensitivity observed in a patient with long-standing ascites secondary to cirrhosis of the liver prompted an investigation of peritoneal sensitivity in 22 patients with the same condition. In all of them a decrease of the peritoneal sensitivity to needle perforation was found. All perceived peritoneal perforation as less painful than perforation of the abdominal skin by the same needle. In 8 control patients perforation of the peritoneum caused more discomfort than the perforation of the skin. In 7 cirrhotic patients where a histologic examination of the parietal peritoneum was available a chronic fibrotic peritonitis was present. Peritoneal insensitivity may partly account for mild abdominal symptoms in cirrhotics developing bacterial peritonitis."} {"id": "PMID:155878", "title": "Potential halogenated industrial carcinogenic and mutagenic chemicals. III. Alkane halides, alkanols and ethers.", "content": "A variety of alkane halides, alkanols and ethers, analogous to the previously considered halogenated unsaturated (Part I) and saturated hydrocarbons (Part II) possess significant utility in a broad spectrum of applications including: solvents, fumigants, propellants and intermediates in the production of other chemicals, textiles, plastics and ion-exchange resins. Ethylene dichloride and dibromide, propylene dichloride; dibromochloropropane; 2-chloroethanol; 1-chloro-2-propanol; 2,3-dibromo-1-propanol; bis(chloromethyl)-, chloromethyl methyl-, bis(2-chloroisopropyl)-, and bis(2-chloroethyl-ethers were reviewed principally in terms of their synthesis, areas of utility, stability, distribution, reactivity, levels of exposure, population at risk, metabolism, carcinogenicity and mutagenicity.", "contents": "Potential halogenated industrial carcinogenic and mutagenic chemicals. III. Alkane halides, alkanols and ethers. A variety of alkane halides, alkanols and ethers, analogous to the previously considered halogenated unsaturated (Part I) and saturated hydrocarbons (Part II) possess significant utility in a broad spectrum of applications including: solvents, fumigants, propellants and intermediates in the production of other chemicals, textiles, plastics and ion-exchange resins. Ethylene dichloride and dibromide, propylene dichloride; dibromochloropropane; 2-chloroethanol; 1-chloro-2-propanol; 2,3-dibromo-1-propanol; bis(chloromethyl)-, chloromethyl methyl-, bis(2-chloroisopropyl)-, and bis(2-chloroethyl-ethers were reviewed principally in terms of their synthesis, areas of utility, stability, distribution, reactivity, levels of exposure, population at risk, metabolism, carcinogenicity and mutagenicity."} {"id": "PMID:155881", "title": "Prolongation of the Q-T interval in a victim of sudden infant death syndrome: cause or effect?", "content": "A 3-week-old infant died of sudden infant death syndrome (crib death, cot death). Although prolongation of the Q-T interval was found on an electrocardiogram taken at birth, this child appeared to have died of terminal respiratory failure as judged by a postmortem arterial oxygen tension of 4 mm Hg. The heart showed right ventricular hypertrophy, a finding consistent with chronic hypoxemia. The prolongation of the Q-T interval may have contributed to the death of this child with hypoxia predisposing to a fatal episode of ventricular fibrillation.", "contents": "Prolongation of the Q-T interval in a victim of sudden infant death syndrome: cause or effect? A 3-week-old infant died of sudden infant death syndrome (crib death, cot death). Although prolongation of the Q-T interval was found on an electrocardiogram taken at birth, this child appeared to have died of terminal respiratory failure as judged by a postmortem arterial oxygen tension of 4 mm Hg. The heart showed right ventricular hypertrophy, a finding consistent with chronic hypoxemia. The prolongation of the Q-T interval may have contributed to the death of this child with hypoxia predisposing to a fatal episode of ventricular fibrillation."} {"id": "PMID:155888", "title": "Radiology as an aid in the diagnosis and management of cardiac diseases.", "content": "Conventional radiology is a routine examination in the diagnosis and management of cardiac diseases. A brief review of its value and limitations is given. A number of technical and/or physiological factors which may influence the cardiopulmonary configuration are mentioned. An approach is suggested for analysis of radiographs of the heart.", "contents": "Radiology as an aid in the diagnosis and management of cardiac diseases. Conventional radiology is a routine examination in the diagnosis and management of cardiac diseases. A brief review of its value and limitations is given. A number of technical and/or physiological factors which may influence the cardiopulmonary configuration are mentioned. An approach is suggested for analysis of radiographs of the heart."} {"id": "PMID:155890", "title": "Immunological monitoring as a guide to the management of transplant recipients.", "content": "Immunological monitoring assays are of current value in the management of transplant recipients. These assays allow the pre-transplant quantitation of both donor-recipient histocompatibility and recipient \"responder status.\" In addition, these assays allow the individualization of immunosuppression, permitting a more uniform and effective immunosuppression in the difficult early post-transplant period. Individualized modulation of recipient immune reactivity avoids the documented pitfalls of conventional stereotyped suppression and permits better abrogation of acute rejection responses and lesser rates of serious infections consequent to excessive immune suppression. Immunological monitoring of long-surviving recipients permits early detection of immune reactivity which often culminates in clinical chronic rejection, as well as permits the quantitation of immune facilitory mechanisms (reduced capability to generate anti-donor cytotoxic T cells and/or cellular suppressor mechanisms) that indicate an immune milieu conductive to long-term graft survival. The primary limitations to the more widespread use of immunological monitoring assays at present are the need for more consensual validations of the utility of these assays in different laboratories, more standardization and better controls of techniques, and improvement in the technology of the assays to permit rapid, reproducible, and accurate results with a lesser expenditure of laboratory time and money and greater economy in demands for recipient blood and donor tissue. Finally, immunological monitoring assays are notable for the great promise they offer in terms of immunobiological probes to dissect mechanisms of rejection, mechanisms of graft facilitation, mechanisms of action of immunosuppressive agents, and mechanisms by which empirical technology of recipient pre-treatment may condition the host to better acceptance of an incompatible graft.", "contents": "Immunological monitoring as a guide to the management of transplant recipients. Immunological monitoring assays are of current value in the management of transplant recipients. These assays allow the pre-transplant quantitation of both donor-recipient histocompatibility and recipient \"responder status.\" In addition, these assays allow the individualization of immunosuppression, permitting a more uniform and effective immunosuppression in the difficult early post-transplant period. Individualized modulation of recipient immune reactivity avoids the documented pitfalls of conventional stereotyped suppression and permits better abrogation of acute rejection responses and lesser rates of serious infections consequent to excessive immune suppression. Immunological monitoring of long-surviving recipients permits early detection of immune reactivity which often culminates in clinical chronic rejection, as well as permits the quantitation of immune facilitory mechanisms (reduced capability to generate anti-donor cytotoxic T cells and/or cellular suppressor mechanisms) that indicate an immune milieu conductive to long-term graft survival. The primary limitations to the more widespread use of immunological monitoring assays at present are the need for more consensual validations of the utility of these assays in different laboratories, more standardization and better controls of techniques, and improvement in the technology of the assays to permit rapid, reproducible, and accurate results with a lesser expenditure of laboratory time and money and greater economy in demands for recipient blood and donor tissue. Finally, immunological monitoring assays are notable for the great promise they offer in terms of immunobiological probes to dissect mechanisms of rejection, mechanisms of graft facilitation, mechanisms of action of immunosuppressive agents, and mechanisms by which empirical technology of recipient pre-treatment may condition the host to better acceptance of an incompatible graft."} {"id": "PMID:155891", "title": "Bronchodilatation and the site of airway resistance in severe chronic bronchitis.", "content": "Twenty-one patients with severe chronic bronchitis and emphysema (FEV1 less than 1 1) inhaled 80 microgram of the atropine-like agent ipratropium or placebo in a double-blind study and three hours later inhaled 200 microgram salbutamol. After 80 microgram ipratropium, mean FEV1 was significantly greater than after 200 microgram salbutamol (P less than 0.025), but the difference was only 40 ml and the clinical significance of this difference is unproved. There was no correlation between the patient's response to ipratropium and the response to salbutamol. When salbutamol was administered three hours after ipratropium, the FEV1 rose to higher levels than after either agent alone (P less than 0.01). Studies breathing 80% helium/20% oxygen suggest that ipratropium dilates both large and small airways. There was no correlation between the response to helium/oxygen and the response to either bronchodilator. The results suggest that in severe chronic bronchitis and emphysema ipratropium is at least as effective as salbutamol, and that such patients should have reversibility studies with salbutamol alone, ipratropium alone, and after both agents together. The combination of ipratropium and salbutamol may be clinically useful.", "contents": "Bronchodilatation and the site of airway resistance in severe chronic bronchitis. Twenty-one patients with severe chronic bronchitis and emphysema (FEV1 less than 1 1) inhaled 80 microgram of the atropine-like agent ipratropium or placebo in a double-blind study and three hours later inhaled 200 microgram salbutamol. After 80 microgram ipratropium, mean FEV1 was significantly greater than after 200 microgram salbutamol (P less than 0.025), but the difference was only 40 ml and the clinical significance of this difference is unproved. There was no correlation between the patient's response to ipratropium and the response to salbutamol. When salbutamol was administered three hours after ipratropium, the FEV1 rose to higher levels than after either agent alone (P less than 0.01). Studies breathing 80% helium/20% oxygen suggest that ipratropium dilates both large and small airways. There was no correlation between the response to helium/oxygen and the response to either bronchodilator. The results suggest that in severe chronic bronchitis and emphysema ipratropium is at least as effective as salbutamol, and that such patients should have reversibility studies with salbutamol alone, ipratropium alone, and after both agents together. The combination of ipratropium and salbutamol may be clinically useful."} {"id": "PMID:155892", "title": "An evaluation of the mini-Wright peak flow meter.", "content": "The mini-Wright peak flow meter (MPFM) has been evaluated, and the results obtained from it show a strong positive correlation (r=0.970) with the Wright's peak flow meter (PFM). MPFM measurements, however, were biased to be about 38 1/min higher than PFM measurements (95% confidence limits 31.01/min to 45.01/min). Between instrument variation was found (F--ratio 3.67 with 9 and 81 degrees of freedom: P less than 0.001). In practice this did not appreciably affect individual measurements greatly as 95% confidence limits on any individual measurements were increased from +/-24 1/min to +/-27 1/min. There was no significant day-to-day variability in measurements obtained with individual instruments. The MPFM is a pocket-sized, simple, cheap, and robust instrument for following changes in ventilatory function. In clinical trails and surveys, however, both the bias in favour of the MPFM compared to the PFM and inter-machine variation must be taken into account. As the manufacturers have altered the scale to remove the bias since this study was performed, it will be important to know whether the original or the modified meter is being used in future studies.", "contents": "An evaluation of the mini-Wright peak flow meter. The mini-Wright peak flow meter (MPFM) has been evaluated, and the results obtained from it show a strong positive correlation (r=0.970) with the Wright's peak flow meter (PFM). MPFM measurements, however, were biased to be about 38 1/min higher than PFM measurements (95% confidence limits 31.01/min to 45.01/min). Between instrument variation was found (F--ratio 3.67 with 9 and 81 degrees of freedom: P less than 0.001). In practice this did not appreciably affect individual measurements greatly as 95% confidence limits on any individual measurements were increased from +/-24 1/min to +/-27 1/min. There was no significant day-to-day variability in measurements obtained with individual instruments. The MPFM is a pocket-sized, simple, cheap, and robust instrument for following changes in ventilatory function. In clinical trails and surveys, however, both the bias in favour of the MPFM compared to the PFM and inter-machine variation must be taken into account. As the manufacturers have altered the scale to remove the bias since this study was performed, it will be important to know whether the original or the modified meter is being used in future studies."} {"id": "PMID:155893", "title": "Coexistence of asymmetric septal hypertrophy and aortic valve disease in adults.", "content": "Echocardiography detected asymmetric septal hypertrophy (ASH) in five of 200 adults being assessed for aortic valve surgery. Four of these were among 119 patients with dominant aortic stenosis, which was severe in three. ASH was confirmed at the time of aortic valve replacement in two of these patients; the third declined operation. The finding of ASH in only one of 81 patients with free aortic reflux is consistent with chance association. While the same explanation could apply to the higher prevalence in those with aortic stenosis, it may be that a long-standing pressure overload can trigger inappropriate septal hypertrophy in predisposed individuals.", "contents": "Coexistence of asymmetric septal hypertrophy and aortic valve disease in adults. Echocardiography detected asymmetric septal hypertrophy (ASH) in five of 200 adults being assessed for aortic valve surgery. Four of these were among 119 patients with dominant aortic stenosis, which was severe in three. ASH was confirmed at the time of aortic valve replacement in two of these patients; the third declined operation. The finding of ASH in only one of 81 patients with free aortic reflux is consistent with chance association. While the same explanation could apply to the higher prevalence in those with aortic stenosis, it may be that a long-standing pressure overload can trigger inappropriate septal hypertrophy in predisposed individuals."} {"id": "PMID:155897", "title": "Standardization of the human in vitro cell-mediated lympholysis technique.", "content": "Cytotoxic lymphocytes (CTL) can be generated in mixed lymphocyte culture and cryopreserved after a 6-day sensitization phase. CTL tested after storage in liquid nitrogen do not show lysis of autologous target cells and can mediate strong cytotoxicity against other target cells. This lysis shows the same specificity as that of the corresponding fresh CTL. The ability to cryopreserve CTL enables performance of sequential CML testing. Data from separate CML experiments can be pooled using a percent relative cytotoxic response (%RCR) to normalize values within individual experiments. Together, these methods provide a standardized cell-mediated lympholysis technique.", "contents": "Standardization of the human in vitro cell-mediated lympholysis technique. Cytotoxic lymphocytes (CTL) can be generated in mixed lymphocyte culture and cryopreserved after a 6-day sensitization phase. CTL tested after storage in liquid nitrogen do not show lysis of autologous target cells and can mediate strong cytotoxicity against other target cells. This lysis shows the same specificity as that of the corresponding fresh CTL. The ability to cryopreserve CTL enables performance of sequential CML testing. Data from separate CML experiments can be pooled using a percent relative cytotoxic response (%RCR) to normalize values within individual experiments. Together, these methods provide a standardized cell-mediated lympholysis technique."} {"id": "PMID:155900", "title": "Kinetic analysis of the placental microsomal 3 beta-hydroxysteroid dehydrogenase activity.", "content": "A sensitive accurate assay for the placental microsomal 3 beta-hydroxysteroid dehydrogenase (E.C.1.1.1.51) has been developed using tritiated substrates. Kinetic analysis of the enzyme with 3 beta-hydroxy-5-androsten-17-one and 3 beta-hydroxy-5-pregnen-20-one indicates that the apparent Km values for these substrates are orders of magnitude less than previously described. Analyses were carried out with microsomal preparations from two different placentas. For placenta 1 the apparent Km value for 3 beta-hydroxy-5-androsten-17-one was 14 nM and for 3 beta-hydroxy-5-pregnen-20-one was 36 nM; for placental 2 apparent Km values were 19 nM and 42 nM respectively. The analyses were performed over wide ranges of substrate concentration (about 200 fold), both above and below the Km values and no deviation from linearity of Eadie-Hoftsee plots was observed.", "contents": "Kinetic analysis of the placental microsomal 3 beta-hydroxysteroid dehydrogenase activity. A sensitive accurate assay for the placental microsomal 3 beta-hydroxysteroid dehydrogenase (E.C.1.1.1.51) has been developed using tritiated substrates. Kinetic analysis of the enzyme with 3 beta-hydroxy-5-androsten-17-one and 3 beta-hydroxy-5-pregnen-20-one indicates that the apparent Km values for these substrates are orders of magnitude less than previously described. Analyses were carried out with microsomal preparations from two different placentas. For placenta 1 the apparent Km value for 3 beta-hydroxy-5-androsten-17-one was 14 nM and for 3 beta-hydroxy-5-pregnen-20-one was 36 nM; for placental 2 apparent Km values were 19 nM and 42 nM respectively. The analyses were performed over wide ranges of substrate concentration (about 200 fold), both above and below the Km values and no deviation from linearity of Eadie-Hoftsee plots was observed."} {"id": "PMID:155906", "title": "Visual acuity at home and in eye clinics.", "content": "Most elderly visually disabled people have lower levels of visual acuity for both reading and getting about in their homes than would be inferred from clinic measurements. Even with optimum optical correction, performance can be much improved by simple modifications to existing facilities, individual advice, and in most cases the addition of a simple adjustable reading lamp.", "contents": "Visual acuity at home and in eye clinics. Most elderly visually disabled people have lower levels of visual acuity for both reading and getting about in their homes than would be inferred from clinic measurements. Even with optimum optical correction, performance can be much improved by simple modifications to existing facilities, individual advice, and in most cases the addition of a simple adjustable reading lamp."} {"id": "PMID:155909", "title": "Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells.", "content": "The in vitro action of the immunosuppressive agent Cyclospirin A has been investigated using porcine cells. Lymphocyte proliferation induced in response to transplantation antigens and phytohaemagglutinin (PHA), was inhibited by this agent at doses that failed to inhibit mitogenisis in response to sheep anti-pig IgM, growth of kidney cell monolayers, and leukocyte migration.", "contents": "Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. The in vitro action of the immunosuppressive agent Cyclospirin A has been investigated using porcine cells. Lymphocyte proliferation induced in response to transplantation antigens and phytohaemagglutinin (PHA), was inhibited by this agent at doses that failed to inhibit mitogenisis in response to sheep anti-pig IgM, growth of kidney cell monolayers, and leukocyte migration."} {"id": "PMID:155911", "title": "Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.", "content": "The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.", "contents": "Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors. The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood."} {"id": "PMID:155912", "title": "Partial characterization of cytotoxic cells infiltrating sponge matrix allografts.", "content": "Adapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term 51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-theta serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens. The following hypotheses are set forth with regard to the cytotoxic lymphocytes (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells.", "contents": "Partial characterization of cytotoxic cells infiltrating sponge matrix allografts. Adapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term 51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-theta serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens. The following hypotheses are set forth with regard to the cytotoxic lymphocytes (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells."} {"id": "PMID:155913", "title": "Minimum length of time required for alloantigen recognition.", "content": "The minimum length of time required for lymph node lymphocytes to recognize alloantigens in vitro was examined in mixed skin cell-lymphocyte culture reactions. Responding lymphocytes in the mixture were successfully separated from stimulating skin cells by Ficoll-Hypaque gradient sedimentation. Lymphocyte activation by allogeneic skin cells took place within 15 min of contact. The amount of measured stimulation was approximately 30% of that produced by an equal concentration of antigen present continuously in culture. The presence of alloantigen was no longer needed after 24 hr. Several control experiments were made in order to exclude the effects of contamination and culture conditions. Identical results were obtained with allogeneic hepatocytes. These data indicate that the recognition of alloantigen leading to lymphocyte proliferation may occur during the early period of contact.", "contents": "Minimum length of time required for alloantigen recognition. The minimum length of time required for lymph node lymphocytes to recognize alloantigens in vitro was examined in mixed skin cell-lymphocyte culture reactions. Responding lymphocytes in the mixture were successfully separated from stimulating skin cells by Ficoll-Hypaque gradient sedimentation. Lymphocyte activation by allogeneic skin cells took place within 15 min of contact. The amount of measured stimulation was approximately 30% of that produced by an equal concentration of antigen present continuously in culture. The presence of alloantigen was no longer needed after 24 hr. Several control experiments were made in order to exclude the effects of contamination and culture conditions. Identical results were obtained with allogeneic hepatocytes. These data indicate that the recognition of alloantigen leading to lymphocyte proliferation may occur during the early period of contact."} {"id": "PMID:155918", "title": "Evaluation of a computer programme for interpretation of 12-lead electrocardiograms.", "content": "A 12-lead electrocardiogram (ECG) interpretation programme (Cardionics, Brussels) was treated for computer diagnosis of ECG. The computer performance was evaluated on an ECG population from hospital patients by a method giving results which will allow the clinician to judge the usefulness of the computer diagnosis in clinical practice. Diagnoses made by experienced ECG readers were in essential agreement with the computer diagnoses in 83.5%, of 493 ECGs. Clinically significant disagreements due to differences in criteria occurred in 6.0% of the tracings, whereas such disagreements due to programme errors were found in 10.5%.", "contents": "Evaluation of a computer programme for interpretation of 12-lead electrocardiograms. A 12-lead electrocardiogram (ECG) interpretation programme (Cardionics, Brussels) was treated for computer diagnosis of ECG. The computer performance was evaluated on an ECG population from hospital patients by a method giving results which will allow the clinician to judge the usefulness of the computer diagnosis in clinical practice. Diagnoses made by experienced ECG readers were in essential agreement with the computer diagnoses in 83.5%, of 493 ECGs. Clinically significant disagreements due to differences in criteria occurred in 6.0% of the tracings, whereas such disagreements due to programme errors were found in 10.5%."} {"id": "PMID:155919", "title": "Experience with a newly developed automatic uroflowmeter.", "content": "An automatic cabin uroflowmeter was developed in order to guarantee the privacy of the patient, to simplify the measurement, and in particular, for screening. The meter is based on the method of von Garrelts, and the registration is performed with a music cassette. After an extensive calibration, 76 measurements from 22 persons without urologic complaints and 42 measurements from patients were analyzed. The obtained values of the control group, as well as those of the patient group were comparable to the data mentioned in literature. A normogram is presented correlating maximum flow rate and voided volume.", "contents": "Experience with a newly developed automatic uroflowmeter. An automatic cabin uroflowmeter was developed in order to guarantee the privacy of the patient, to simplify the measurement, and in particular, for screening. The meter is based on the method of von Garrelts, and the registration is performed with a music cassette. After an extensive calibration, 76 measurements from 22 persons without urologic complaints and 42 measurements from patients were analyzed. The obtained values of the control group, as well as those of the patient group were comparable to the data mentioned in literature. A normogram is presented correlating maximum flow rate and voided volume."} {"id": "PMID:155920", "title": "[Types of urination in men according to urodynamic flow measurement data].", "content": "The work is grounded on the analysis of the urination parameters, obtained from the examination of 195 men with various urological pathologies and of 100 healthy individuals, through urodynamofluometry--a new method of the express-diagnosis of the urination disorders. 5 types of the urination according to its volume have been distinguished. The devised system of the quantitative-qualitative evaluation of the urination is an attempt to differentiate various conditions of the urodynamics of the lower urinary passages versus the peculiarities of their anatomo-functional state in men.", "contents": "[Types of urination in men according to urodynamic flow measurement data]. The work is grounded on the analysis of the urination parameters, obtained from the examination of 195 men with various urological pathologies and of 100 healthy individuals, through urodynamofluometry--a new method of the express-diagnosis of the urination disorders. 5 types of the urination according to its volume have been distinguished. The devised system of the quantitative-qualitative evaluation of the urination is an attempt to differentiate various conditions of the urodynamics of the lower urinary passages versus the peculiarities of their anatomo-functional state in men."} {"id": "PMID:155925", "title": "[Phage relationships of coagulase-positive staphylococci isolated from raw and pasteurized cow's milk].", "content": "Studied is the behaviour to phages of 136 strains of coagulase positive cstaphylococci, isolated from raw (82), pasteurized milk stored in tanks (30) and pasteurized milk in bottles (24). The Staphylococcus aureus strains investigated are sensitive to bovine phages and, above all, to those of the 4th group (102, 107, 117 and 42D) or in combination with them. No lyses are established in the 1st and 3rd phage groups. The 107/117 and 107/117/42D are the phage types most frequently identified. The same phage types are found in both raw and pasteurized cow milk. It is established that 82 per cent of the Staphylococcus aureus strains studied with the rystal-violet test belong to types A and B after Meyer.", "contents": "[Phage relationships of coagulase-positive staphylococci isolated from raw and pasteurized cow's milk]. Studied is the behaviour to phages of 136 strains of coagulase positive cstaphylococci, isolated from raw (82), pasteurized milk stored in tanks (30) and pasteurized milk in bottles (24). The Staphylococcus aureus strains investigated are sensitive to bovine phages and, above all, to those of the 4th group (102, 107, 117 and 42D) or in combination with them. No lyses are established in the 1st and 3rd phage groups. The 107/117 and 107/117/42D are the phage types most frequently identified. The same phage types are found in both raw and pasteurized cow milk. It is established that 82 per cent of the Staphylococcus aureus strains studied with the rystal-violet test belong to types A and B after Meyer."} {"id": "PMID:155928", "title": "Argyrophil pituitary tumors showing TSH cells or small granule cells.", "content": "Among 74 histochemically and ultrastructurally studied pituitary adenomas, 12 apparently chromophobe tumors were characterized by the presence of numerous argyrophil cells. All these argyrophil adenomas failed to reveal presence of GH, prolactin or ACTH cells. Two tumors were found to consist of well granulated cells reacting intensely with anti-TSH antibodies and resembling TSH cells of the normal pituitary. The remaining argyrophil adenomas did not show TSH immunostaining and, with one exception, failed to react with an anti-HCG serum staining gonadotroph cells of human pituitary. They were composed of small, closely apposed cells with small compact or vesicular granules. These tumor cells seem to correspond to some small argyrophil cells found in non-neoplastic pituitary, which differ from TSH cells and from all other types of functionally identified adenohypophyseal cells.", "contents": "Argyrophil pituitary tumors showing TSH cells or small granule cells. Among 74 histochemically and ultrastructurally studied pituitary adenomas, 12 apparently chromophobe tumors were characterized by the presence of numerous argyrophil cells. All these argyrophil adenomas failed to reveal presence of GH, prolactin or ACTH cells. Two tumors were found to consist of well granulated cells reacting intensely with anti-TSH antibodies and resembling TSH cells of the normal pituitary. The remaining argyrophil adenomas did not show TSH immunostaining and, with one exception, failed to react with an anti-HCG serum staining gonadotroph cells of human pituitary. They were composed of small, closely apposed cells with small compact or vesicular granules. These tumor cells seem to correspond to some small argyrophil cells found in non-neoplastic pituitary, which differ from TSH cells and from all other types of functionally identified adenohypophyseal cells."} {"id": "PMID:155929", "title": "Glomerulonephritis induced by high doses of ovalbumin. Studies by electron microscopy, immunofluorescence and immuno-electron microscopy.", "content": "Experimental glomerulonephritis was produced in 16 rabbits by intravenous injections of ovalbumin in high doses (0.1 g/day during the first week, 0.2 g x 6/day during the second). The animals were killed on day 14. At that time all animals had 2--4+ proteinuria and a serum C3 level reduced to about 50% of the control level; 11 animals had a significantly raised blood urea level. In all rabbits the antigen had induced severe proliferative glomerulonephritis. Electron microscopy showed that many of the cells accounting for the hypercellularity were monocytes. Surprisingly, electron dense deposits were few and small, mainly on the subendothelial and subepithelial aspects of the glomerular basement membrane. In all the animals ultrastructural immunoperoxidase technique revealed deposits containing ovalbumin, rabbit IgG and C3. With immunofluorescence sparse deposits were occasionally seen. It is concluded that a severe experimental glomerulonephritis can be produced in a state of antigen excess, with the deposition of immune complexes being minimal. Immuno-electron microscopy is essential, however, in detecting even the smallest animals of deposited immune reactants.", "contents": "Glomerulonephritis induced by high doses of ovalbumin. Studies by electron microscopy, immunofluorescence and immuno-electron microscopy. Experimental glomerulonephritis was produced in 16 rabbits by intravenous injections of ovalbumin in high doses (0.1 g/day during the first week, 0.2 g x 6/day during the second). The animals were killed on day 14. At that time all animals had 2--4+ proteinuria and a serum C3 level reduced to about 50% of the control level; 11 animals had a significantly raised blood urea level. In all rabbits the antigen had induced severe proliferative glomerulonephritis. Electron microscopy showed that many of the cells accounting for the hypercellularity were monocytes. Surprisingly, electron dense deposits were few and small, mainly on the subendothelial and subepithelial aspects of the glomerular basement membrane. In all the animals ultrastructural immunoperoxidase technique revealed deposits containing ovalbumin, rabbit IgG and C3. With immunofluorescence sparse deposits were occasionally seen. It is concluded that a severe experimental glomerulonephritis can be produced in a state of antigen excess, with the deposition of immune complexes being minimal. Immuno-electron microscopy is essential, however, in detecting even the smallest animals of deposited immune reactants."} {"id": "PMID:155930", "title": "[On the pathology of acute heart failure in bronchial asthma (author's transl)].", "content": "In cases dying with asthma, heart muscle stained by the Haematoxylin-basic-Fuchsin-Pikric acid-method showed multiple areas of focal ischaemic injury of single or small groups of muscle fibres. The localisation of these changes in the inner layers of the wall and septum of the ventricle and the pattern of the changes produced, suggest poor coronary perfusion. The changes are explained as the result of combined damage due to hypoxic circulatory disturbances of the heart muscle and the effects of catecholamines. The appearances may provide the morphological basis for accurate diagnosis.", "contents": "[On the pathology of acute heart failure in bronchial asthma (author's transl)]. In cases dying with asthma, heart muscle stained by the Haematoxylin-basic-Fuchsin-Pikric acid-method showed multiple areas of focal ischaemic injury of single or small groups of muscle fibres. The localisation of these changes in the inner layers of the wall and septum of the ventricle and the pattern of the changes produced, suggest poor coronary perfusion. The changes are explained as the result of combined damage due to hypoxic circulatory disturbances of the heart muscle and the effects of catecholamines. The appearances may provide the morphological basis for accurate diagnosis."} {"id": "PMID:155931", "title": "Intrauterine wound healing in a 20 week human fetus.", "content": "Limb amputations, probably caused by amniotic constriction bands, were examined histologically in a 20 week human fetus to assess the degree of intrauterine healing. No acute inflammatory process, no removal of necrotic material, and no granulation tissue formation were seen at any of the amputation sites. A recent ulcer, probably caused by friction of an exposed piece of bone in the stump of the right leg, also showed no inflammatory response. Healing was by coagulation of exposed tissue and by a minor degree of mesenchymal proliferation without repair. Similar changes have been described in experimental intrauterine wound healing in rats, lambs, opossums and baboons. Conversion from a non-specific to a classical postnatal inflammatory response occurs sometime before term. It is not known at what point this change takes place in man; examination of this infant suggests that it occurs after the twentieth week of gestation.", "contents": "Intrauterine wound healing in a 20 week human fetus. Limb amputations, probably caused by amniotic constriction bands, were examined histologically in a 20 week human fetus to assess the degree of intrauterine healing. No acute inflammatory process, no removal of necrotic material, and no granulation tissue formation were seen at any of the amputation sites. A recent ulcer, probably caused by friction of an exposed piece of bone in the stump of the right leg, also showed no inflammatory response. Healing was by coagulation of exposed tissue and by a minor degree of mesenchymal proliferation without repair. Similar changes have been described in experimental intrauterine wound healing in rats, lambs, opossums and baboons. Conversion from a non-specific to a classical postnatal inflammatory response occurs sometime before term. It is not known at what point this change takes place in man; examination of this infant suggests that it occurs after the twentieth week of gestation."} {"id": "PMID:155934", "title": "[Severe diphtheria with acute myocardial infarction (author's transl)].", "content": "Report on a female patient with severe diphtheria and electrocardiographic changes of acute myocardial infarction. Cases of such a kind seem to be seldom, as a review of international literature shows.", "contents": "[Severe diphtheria with acute myocardial infarction (author's transl)]. Report on a female patient with severe diphtheria and electrocardiographic changes of acute myocardial infarction. Cases of such a kind seem to be seldom, as a review of international literature shows."} {"id": "PMID:155939", "title": "Histochemical observations on the taste buds of the marmosets (Callithrix jacchus and Callithrix penicillata).", "content": "The epithelial cells in the taste buds of C. jacchus and C. penicillata show a moderate amount of ribonucleic acid an a concentration of a PAS-positive diastase-resistant material at their apical part. These cells are devoid of UDPG-GT, phosphorylases, G-6-PA, alanyl aminopeptidase, leucine aminopeptidase, cholinesterase and MAO; they present a weak reaction of F-1, 6-P Ald, LDH, SDH, MDH, cytochrome oxidase, beta-OHBDH, nonspecific esterase and acid phosphatase and a stronger reaction to ADH, NADPH2-TR, ATPases, alpha-GPDH, alkaline phosphatase, 5-nucleotidase and GDH. Although some enzymes (alkaline phosphatase, 5-nucleotidase and ATPases) have an almost uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller taste buds of the fungiform papillae. As a rule the apical part of the cells shows a stronger enzymatic reactivity. The taste buds of the marmosets are penetrated by acetylcholinesterase positive nerve fibers whereas the autonomic ganglia in the connective tissue contain both-acetyl and butyrylcholinesterase.", "contents": "Histochemical observations on the taste buds of the marmosets (Callithrix jacchus and Callithrix penicillata). The epithelial cells in the taste buds of C. jacchus and C. penicillata show a moderate amount of ribonucleic acid an a concentration of a PAS-positive diastase-resistant material at their apical part. These cells are devoid of UDPG-GT, phosphorylases, G-6-PA, alanyl aminopeptidase, leucine aminopeptidase, cholinesterase and MAO; they present a weak reaction of F-1, 6-P Ald, LDH, SDH, MDH, cytochrome oxidase, beta-OHBDH, nonspecific esterase and acid phosphatase and a stronger reaction to ADH, NADPH2-TR, ATPases, alpha-GPDH, alkaline phosphatase, 5-nucleotidase and GDH. Although some enzymes (alkaline phosphatase, 5-nucleotidase and ATPases) have an almost uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller taste buds of the fungiform papillae. As a rule the apical part of the cells shows a stronger enzymatic reactivity. The taste buds of the marmosets are penetrated by acetylcholinesterase positive nerve fibers whereas the autonomic ganglia in the connective tissue contain both-acetyl and butyrylcholinesterase."} {"id": "PMID:155936", "title": "Unusually high occurrence of drug reactions with nafcillin.", "content": "Five patients seen during a two-month period who developed untoward systemic reactions following high dose intravenous administration of nafcillin are described. Recovery was complete upon discontinuation of the drug. The clustering of these cases and the high incidence (5 of 5) of side effects are highly unusual, and suggest that the frequency of nafcillin reactions might be higher than previously suspected.", "contents": "Unusually high occurrence of drug reactions with nafcillin. Five patients seen during a two-month period who developed untoward systemic reactions following high dose intravenous administration of nafcillin are described. Recovery was complete upon discontinuation of the drug. The clustering of these cases and the high incidence (5 of 5) of side effects are highly unusual, and suggest that the frequency of nafcillin reactions might be higher than previously suspected."} {"id": "PMID:155940", "title": "Cultured lung cells: interplay effects of beta-mimetics, prostaglandins and corticosteroids in the biosynthesis of dipalmitoyl lecithin.", "content": "Cell lines derived from type II lung cells were used to study interplays of substances affecting incorporation of labeled precursors [1(-14)C]palmitate and [methyl-3H]choline into phosphatidyl choline. Ethanol stimulated markedly biosynthesis of dipalmitoyl phosphatidyl choline in cloned rabbit lung cells; the stimulating action of ethanol was reduced very much by cortisol and less by ritodrine. In the presence of 0.1 microM isoproterenol, two prostaglandins, E2 and F2alpha, caused marked depressions in the incorporation of both precursors by cell line A 549 derived from human lung adenocarcinoma. One concluded that among the agents studied, ethanol and cortisol are potent antagonists, and so were also the prostaglandins and isoproterenol.", "contents": "Cultured lung cells: interplay effects of beta-mimetics, prostaglandins and corticosteroids in the biosynthesis of dipalmitoyl lecithin. Cell lines derived from type II lung cells were used to study interplays of substances affecting incorporation of labeled precursors [1(-14)C]palmitate and [methyl-3H]choline into phosphatidyl choline. Ethanol stimulated markedly biosynthesis of dipalmitoyl phosphatidyl choline in cloned rabbit lung cells; the stimulating action of ethanol was reduced very much by cortisol and less by ritodrine. In the presence of 0.1 microM isoproterenol, two prostaglandins, E2 and F2alpha, caused marked depressions in the incorporation of both precursors by cell line A 549 derived from human lung adenocarcinoma. One concluded that among the agents studied, ethanol and cortisol are potent antagonists, and so were also the prostaglandins and isoproterenol."} {"id": "PMID:155941", "title": "[The in vitro and in vivo stability of the entrapment of methotrexate in negatively charged liposomes after sterile filtration (author's transl)].", "content": "The preparation of sterile artificial liposomes (phosphatidylcholine:cholesterol:dicethylphosphate=5:5:1) by Millipore filtration is described. Conditions for storing liposome entrapped Methotrexate have been found which allow storage of the drug in the entrapped form over a period of at least 4 months. It is shown that intravenously injected liposome entrapped Methotrexate is retained for at least 15 hours in the particulate form. During this time no free Methotrexate is detectable in the blood.", "contents": "[The in vitro and in vivo stability of the entrapment of methotrexate in negatively charged liposomes after sterile filtration (author's transl)]. The preparation of sterile artificial liposomes (phosphatidylcholine:cholesterol:dicethylphosphate=5:5:1) by Millipore filtration is described. Conditions for storing liposome entrapped Methotrexate have been found which allow storage of the drug in the entrapped form over a period of at least 4 months. It is shown that intravenously injected liposome entrapped Methotrexate is retained for at least 15 hours in the particulate form. During this time no free Methotrexate is detectable in the blood."} {"id": "PMID:155942", "title": "Enhanced melanization of Harding-Passey mouse melanoma cells following treatment with exogenous melanosomes in monolayer culture.", "content": "Purified melanosomes isolated from subcutaneously growting Harding-Passey melanomas of NMRI-mice were labeled either in vitro with [14C]tyrosine or [14C]DOPA in the melanin portion, or in vivo in the melanin and protein portion following i. p. injection of [14C]tyrosine. Treatment of monolayer cultures of Harding-Passey melanoma cells (HPM-73 line) with such labeled melanosomes resulted in rapid uptake of label during the first 4 h which leveled off thereafter. A portion of the \"incorporated\" label could be removed by a 15 min chase with unlabeled melanosomes. Uptake of labeled melanosomes by HPM-73 cells was followed by increased cellular melanization which was not only due to melanin derived from incorporated melanosomes but primarily to newly formed melanin. Tyrosinase activity was elevated in melanosome-treated cells. Tyrosinase activity of control cells was significantly reduced following a 24 h exposure to actinomycin D or cycloheximide. On the other side, the same inhibitor treatment of melanosome-pretreated cells resulted in less inhibition of tyrosinase activity. The present findings suggest \"melanophagic\" properties of cultured melanoma cells resulting in enhanced melanogenesis after phagocytotic uptake of functionally active exogenous melanosomes.", "contents": "Enhanced melanization of Harding-Passey mouse melanoma cells following treatment with exogenous melanosomes in monolayer culture. Purified melanosomes isolated from subcutaneously growting Harding-Passey melanomas of NMRI-mice were labeled either in vitro with [14C]tyrosine or [14C]DOPA in the melanin portion, or in vivo in the melanin and protein portion following i. p. injection of [14C]tyrosine. Treatment of monolayer cultures of Harding-Passey melanoma cells (HPM-73 line) with such labeled melanosomes resulted in rapid uptake of label during the first 4 h which leveled off thereafter. A portion of the \"incorporated\" label could be removed by a 15 min chase with unlabeled melanosomes. Uptake of labeled melanosomes by HPM-73 cells was followed by increased cellular melanization which was not only due to melanin derived from incorporated melanosomes but primarily to newly formed melanin. Tyrosinase activity was elevated in melanosome-treated cells. Tyrosinase activity of control cells was significantly reduced following a 24 h exposure to actinomycin D or cycloheximide. On the other side, the same inhibitor treatment of melanosome-pretreated cells resulted in less inhibition of tyrosinase activity. The present findings suggest \"melanophagic\" properties of cultured melanoma cells resulting in enhanced melanogenesis after phagocytotic uptake of functionally active exogenous melanosomes."} {"id": "PMID:155944", "title": "Osmotic sensitivity and tolerance and proteinase production in a strain of Saccharomyces.", "content": "A brewing yeast strain, NCYC 1085, unusual in that it sporulated freely and produced diploid spores, was sensitive to the degree of osmotic tension induced by the addition of 1.5 M KC1 or 2.5 M ethylene glycol to yeast extract-peptone glucose medium, but its progeny, obtained on sporulation and dissection of the resulting asci, included a number of osmotic-tolerant strains, the percentage of which increased as these strains were also sporulated and dissected. In addition, after repeated isolation of single-spore clones for three or four generations, clones producing zones of liquefaction of gelatin ranging in size from zero to large (approximately 1.5 cm) appeared, with the intensity of hydrolysis increasing in clones obtained from the later generations. The isolation of erythromycin-resistant mutants by manganese treatment was also accompanied by the appearance of osmotic-tolerant and gelatin-liquefying clones.", "contents": "Osmotic sensitivity and tolerance and proteinase production in a strain of Saccharomyces. A brewing yeast strain, NCYC 1085, unusual in that it sporulated freely and produced diploid spores, was sensitive to the degree of osmotic tension induced by the addition of 1.5 M KC1 or 2.5 M ethylene glycol to yeast extract-peptone glucose medium, but its progeny, obtained on sporulation and dissection of the resulting asci, included a number of osmotic-tolerant strains, the percentage of which increased as these strains were also sporulated and dissected. In addition, after repeated isolation of single-spore clones for three or four generations, clones producing zones of liquefaction of gelatin ranging in size from zero to large (approximately 1.5 cm) appeared, with the intensity of hydrolysis increasing in clones obtained from the later generations. The isolation of erythromycin-resistant mutants by manganese treatment was also accompanied by the appearance of osmotic-tolerant and gelatin-liquefying clones."} {"id": "PMID:155946", "title": "Phenylalanyl-tRNA synthetase from baker's yeast: structural organization of the enzyme and its complex with tRNAPhe as determined by X-ray small-angle scattering.", "content": "The quaternary structure of the phenylalanyl-tRNA synthetase and its complex with tRNAPhe was studied in dilute solutions by small angle X-ray scattering. For the free synthetase the radius of gyration was determined as 5.5 nm, the volume 523 nm3, the maximum diameter 17.5 nm and the molecular weight as 260,000 using an isopotential specific volume of 0.735. The overall shape could be best approximated by a flat cylinder with dimensions 18.2 nmx11.5 nmx4nm; the loose structure was approximated by building up the cylinder by spheres (diameter 4.2 nm). The corresponding parameters of the enzyme tRNA complex were the following: radius of gyration 5.9 nm, volume 543 nm3, maximum diameter 21 nm and molecular weight 290,000. These parameters suggest an 1:1 complex, whereby it must be assumed that the tRNA molecule is attached in the extension of the longer axis. From the difference in the distance distribution functions of the free enzyme and the complex it is evident that we have to assume a change of conformation (contraction) of the enzyme upon the binding of the specific tRNA.", "contents": "Phenylalanyl-tRNA synthetase from baker's yeast: structural organization of the enzyme and its complex with tRNAPhe as determined by X-ray small-angle scattering. The quaternary structure of the phenylalanyl-tRNA synthetase and its complex with tRNAPhe was studied in dilute solutions by small angle X-ray scattering. For the free synthetase the radius of gyration was determined as 5.5 nm, the volume 523 nm3, the maximum diameter 17.5 nm and the molecular weight as 260,000 using an isopotential specific volume of 0.735. The overall shape could be best approximated by a flat cylinder with dimensions 18.2 nmx11.5 nmx4nm; the loose structure was approximated by building up the cylinder by spheres (diameter 4.2 nm). The corresponding parameters of the enzyme tRNA complex were the following: radius of gyration 5.9 nm, volume 543 nm3, maximum diameter 21 nm and molecular weight 290,000. These parameters suggest an 1:1 complex, whereby it must be assumed that the tRNA molecule is attached in the extension of the longer axis. From the difference in the distance distribution functions of the free enzyme and the complex it is evident that we have to assume a change of conformation (contraction) of the enzyme upon the binding of the specific tRNA."} {"id": "PMID:155947", "title": "[The acetylcholinesterase of Bungarus multicinctus venom. Purification and properties (author's transl)].", "content": "Acetylcholinesterase from Banded krait (Bungarus multicinctus) venom has been purified by CM-Sephadex chromatography and affinity chromatography to a specific activity of 4290 U/mg. The purified enzyme is a glycoprotein. It is free of electrophoretically detectable contaminating proteins. A molecular weight of 140,000 +/- 5,000 has been determined by gradient gel electrophoresis for the native enzyme. It is split into two equal-sized subunits (Mr 70,000 +/- 2,000) by SDS treatment. The N-terminal amino acid analysis gave glycine and serine. The purified acetylcholinesterase can be resolved by disc gel electrophoresis into four and by isoelectric focusing into six isozymes. The pI value of the main isozyme has been found to be 5.98 +/- 0.05.", "contents": "[The acetylcholinesterase of Bungarus multicinctus venom. Purification and properties (author's transl)]. Acetylcholinesterase from Banded krait (Bungarus multicinctus) venom has been purified by CM-Sephadex chromatography and affinity chromatography to a specific activity of 4290 U/mg. The purified enzyme is a glycoprotein. It is free of electrophoretically detectable contaminating proteins. A molecular weight of 140,000 +/- 5,000 has been determined by gradient gel electrophoresis for the native enzyme. It is split into two equal-sized subunits (Mr 70,000 +/- 2,000) by SDS treatment. The N-terminal amino acid analysis gave glycine and serine. The purified acetylcholinesterase can be resolved by disc gel electrophoresis into four and by isoelectric focusing into six isozymes. The pI value of the main isozyme has been found to be 5.98 +/- 0.05."} {"id": "PMID:155943", "title": "Stained native collagen: interpretation of the small angle X-ray scattering and electron microscopic pictures in terms of the primary structure.", "content": "The average axial electron-density distribution of stained collagen fibers derived from X-ray small angle pattern, is shown to be substantially related to the projection of the polar amino acid residues onto the axis of the microfibril taking into consideration the staggering of neighbouring molecules. In order to arrive ultimately at a quantitative representation of the experimental data, an additional periodic fluctuation of the density in direction of the fibril axis is required. The necessity of this regular microphase structure for an understanding of known physical properties of collagen fibers will be indicated.", "contents": "Stained native collagen: interpretation of the small angle X-ray scattering and electron microscopic pictures in terms of the primary structure. The average axial electron-density distribution of stained collagen fibers derived from X-ray small angle pattern, is shown to be substantially related to the projection of the polar amino acid residues onto the axis of the microfibril taking into consideration the staggering of neighbouring molecules. In order to arrive ultimately at a quantitative representation of the experimental data, an additional periodic fluctuation of the density in direction of the fibril axis is required. The necessity of this regular microphase structure for an understanding of known physical properties of collagen fibers will be indicated."} {"id": "PMID:155948", "title": "Assimilatory nitrate reductase of Rhodopseudomonas capsulata AD2: a molybdo-hemeprotein.", "content": "The assimilatory nitrate reductase of the phototrophic bacterium Rhodopseudomonas capsulata strain AD2 was purified to homogeneity by a combination of ammonium sulfate fractionation, chromatography on DEAE-cellulose and isoelectric focusing (isoelectric point of 4.8). The purified enzyme was active only with reduced viologen dyes or reduced flavin as electron donors. Contrary to other bacterial assimilatory nitrate reductases, the enzyme was not inhibited by chlorate, but rather accepted this substance as an alternate substrate. The molecular weight of the enzyme was 185,000 dalton as determined by gelfiltration. Subunit analysis by sodium dodecyl sulfate (SDS) gel electrophoresis yielded a single protein band with a molecular weight of 85,000 dalton,, suggesting that the enzyme was composed of two identical subunits. The nitrate reductase contained 0.8 g-atoms molybdenum per 1.85 x 10(5) g protein and exhibited absorption maxima at 418, 523 and 552 nm in the reduced state (dithionite as reductant). The nitrate reductase of Rps. capsulata AD2 is the first prokaryotic enzyme of the assimilatory type that has been shown to contain heme.", "contents": "Assimilatory nitrate reductase of Rhodopseudomonas capsulata AD2: a molybdo-hemeprotein. The assimilatory nitrate reductase of the phototrophic bacterium Rhodopseudomonas capsulata strain AD2 was purified to homogeneity by a combination of ammonium sulfate fractionation, chromatography on DEAE-cellulose and isoelectric focusing (isoelectric point of 4.8). The purified enzyme was active only with reduced viologen dyes or reduced flavin as electron donors. Contrary to other bacterial assimilatory nitrate reductases, the enzyme was not inhibited by chlorate, but rather accepted this substance as an alternate substrate. The molecular weight of the enzyme was 185,000 dalton as determined by gelfiltration. Subunit analysis by sodium dodecyl sulfate (SDS) gel electrophoresis yielded a single protein band with a molecular weight of 85,000 dalton,, suggesting that the enzyme was composed of two identical subunits. The nitrate reductase contained 0.8 g-atoms molybdenum per 1.85 x 10(5) g protein and exhibited absorption maxima at 418, 523 and 552 nm in the reduced state (dithionite as reductant). The nitrate reductase of Rps. capsulata AD2 is the first prokaryotic enzyme of the assimilatory type that has been shown to contain heme."} {"id": "PMID:155949", "title": "Purification, subunit structure, and kinetics of the chloroform-released F1ATPase complex from Rhodospirillum rubrum and its comparison with F1ATPase forms isolated by other methods.", "content": "A stable and homogeneous adenosine-5'-triphosphatase (ATPase, EC 3.6.1.3) has been solubilized from Rhodospirillum rubrum (R. rubrum) chromatophores by chloroform extraction. Purification of the Ca2+-dependent ATPase activity was 200-fold. Ca2+ can be replaced by Mg2+, Cd2+, and Mn2+. The Km for Ca-ATP (0.17 mM) is increased about 5-fold during solubilization of the enzyme, whereas the Km values for Mg-ATP (0.029 mM) and Cd-ATP (0.014 mM) are not affected. The chloroform-released ATPase has a molecular weight of 400,000 +/- 30,000 and consists of the following subunits (molecular weights in parenthesis): alpha(58,000), beta(53,500), gamma(39,000), delta(18,500), and epsilon(14,000). The amino acid composition and the fluorescence spectra are presented. Besides the chloroform-released ATPase complex three other Ca2+-dependent ATPase forms have been isolated from R. rubrum chromatophores by other methods for comparison. Ultrasonication of the membranes leads to the release of an ATPase complex which is mainly composed of alpha, beta, and gamma-subunits. From an acetone powder extract an ATPase complex could be purified by affinity chromatography which is composed of four kinds of subunits (alpha, beta, gamma, delta). The same acetone powder yields an ATPase consisting of only three different types of subunits (alpha, beta, gamma) if the final purification step is preparative disc electrophoresis on 6% polyacrylamide gels instead of affinity chromatography.", "contents": "Purification, subunit structure, and kinetics of the chloroform-released F1ATPase complex from Rhodospirillum rubrum and its comparison with F1ATPase forms isolated by other methods. A stable and homogeneous adenosine-5'-triphosphatase (ATPase, EC 3.6.1.3) has been solubilized from Rhodospirillum rubrum (R. rubrum) chromatophores by chloroform extraction. Purification of the Ca2+-dependent ATPase activity was 200-fold. Ca2+ can be replaced by Mg2+, Cd2+, and Mn2+. The Km for Ca-ATP (0.17 mM) is increased about 5-fold during solubilization of the enzyme, whereas the Km values for Mg-ATP (0.029 mM) and Cd-ATP (0.014 mM) are not affected. The chloroform-released ATPase has a molecular weight of 400,000 +/- 30,000 and consists of the following subunits (molecular weights in parenthesis): alpha(58,000), beta(53,500), gamma(39,000), delta(18,500), and epsilon(14,000). The amino acid composition and the fluorescence spectra are presented. Besides the chloroform-released ATPase complex three other Ca2+-dependent ATPase forms have been isolated from R. rubrum chromatophores by other methods for comparison. Ultrasonication of the membranes leads to the release of an ATPase complex which is mainly composed of alpha, beta, and gamma-subunits. From an acetone powder extract an ATPase complex could be purified by affinity chromatography which is composed of four kinds of subunits (alpha, beta, gamma, delta). The same acetone powder yields an ATPase consisting of only three different types of subunits (alpha, beta, gamma) if the final purification step is preparative disc electrophoresis on 6% polyacrylamide gels instead of affinity chromatography."} {"id": "PMID:155945", "title": "Methylmercury-induced sedimentation heterogeneity of T7 bacteriophage DNA.", "content": "Single-stranded and methylmercurated T7 DNA is composed of two species as evidenced from the sedimentation pattern displayed during band-sedimentation in self-generating density gradients as well as during equilibrium-sedimentation in CS2SO4 density gradients. Under the given experimental conditions, viz., at pH 9.18 and in presence of 0.1 mM CH3HgOH, the two species band in CS2SO4 with a density difference of 0.008 g/ml. The ratio of the sedimentation coefficients of the two species is sw, 20 (fast)/sw, 20 (slow) = 1.63 at pH 9.18 and in presence of 1.6 mM CH3HgOH. Both native and denatured T7 DNA behave as monodisperse systems in the absence of CH3HgOH.", "contents": "Methylmercury-induced sedimentation heterogeneity of T7 bacteriophage DNA. Single-stranded and methylmercurated T7 DNA is composed of two species as evidenced from the sedimentation pattern displayed during band-sedimentation in self-generating density gradients as well as during equilibrium-sedimentation in CS2SO4 density gradients. Under the given experimental conditions, viz., at pH 9.18 and in presence of 0.1 mM CH3HgOH, the two species band in CS2SO4 with a density difference of 0.008 g/ml. The ratio of the sedimentation coefficients of the two species is sw, 20 (fast)/sw, 20 (slow) = 1.63 at pH 9.18 and in presence of 1.6 mM CH3HgOH. Both native and denatured T7 DNA behave as monodisperse systems in the absence of CH3HgOH."} {"id": "PMID:155950", "title": "Evidence for the existence of meta and para directing O-methyltransferases in tobacco cell cultures.", "content": "The O-methyltransferase of tobacco cell culture was resolved to its meta and para directing forms by chromatography on DEAE-cellulose. Despite similarities in molecular weights and pI values of the two forms, however, evidence from pH optima, SH-group inhibitors, methylation ratios, SDS-acrylamide gels and mixed substrate experiments indicates the existence of two discrete enzymes acting at the meta and para positions of caffeic acid and quercetin, respectively; though the latter enzyme was less substrate specific than its meta counterpart.", "contents": "Evidence for the existence of meta and para directing O-methyltransferases in tobacco cell cultures. The O-methyltransferase of tobacco cell culture was resolved to its meta and para directing forms by chromatography on DEAE-cellulose. Despite similarities in molecular weights and pI values of the two forms, however, evidence from pH optima, SH-group inhibitors, methylation ratios, SDS-acrylamide gels and mixed substrate experiments indicates the existence of two discrete enzymes acting at the meta and para positions of caffeic acid and quercetin, respectively; though the latter enzyme was less substrate specific than its meta counterpart."} {"id": "PMID:155951", "title": "Search for millimeter microwave effects on enzyme or protein functions.", "content": "Recent observations of nonthermal, resonant biological responses to weak millimeter microwave irradiation have led us to investigate whether similar influences exist on enzymatic functions in vitro. We chose (i) the reduction of ethanol in the presence of alcohol dehydrogenase and (ii) the cooperative binding of oxygen on hemoglobin. Using an irradiation intensity near 10 mW/cm2 the frequency was continuously varied from 40 to 115 GHz with a resolution of a few MHz. No microwave influences were detectable within our experimental sensitivity of about 0.1% of the reaction rate in (i), or of the amount of bound oxygen at half saturation in (ii).", "contents": "Search for millimeter microwave effects on enzyme or protein functions. Recent observations of nonthermal, resonant biological responses to weak millimeter microwave irradiation have led us to investigate whether similar influences exist on enzymatic functions in vitro. We chose (i) the reduction of ethanol in the presence of alcohol dehydrogenase and (ii) the cooperative binding of oxygen on hemoglobin. Using an irradiation intensity near 10 mW/cm2 the frequency was continuously varied from 40 to 115 GHz with a resolution of a few MHz. No microwave influences were detectable within our experimental sensitivity of about 0.1% of the reaction rate in (i), or of the amount of bound oxygen at half saturation in (ii)."} {"id": "PMID:155954", "title": "In vitro action of gastric mucosal lysosomal enzymes on intracellular gastric glycoproteins.", "content": "The results show that incubation of gastric mucosal cells from rat at pH approximately 4.5 or in the presence of aspirin is associated with a specific increase in the activity of some acid-hydrolases. Intracellular glycoproteins, isolated by non-degrative techniques from rat or dog fundic mucosal cells, were found to be potential bio-substrates for these acid-hydrolyses. This may suggest that cleavage of the carbohydrate moieties of the intracellular and mucosal cell wall glycoproteins is a fundamental step in the development of gastric ulceration. A model for gastric lesions is proposed and discussed in the light of the results obtained.", "contents": "In vitro action of gastric mucosal lysosomal enzymes on intracellular gastric glycoproteins. The results show that incubation of gastric mucosal cells from rat at pH approximately 4.5 or in the presence of aspirin is associated with a specific increase in the activity of some acid-hydrolases. Intracellular glycoproteins, isolated by non-degrative techniques from rat or dog fundic mucosal cells, were found to be potential bio-substrates for these acid-hydrolyses. This may suggest that cleavage of the carbohydrate moieties of the intracellular and mucosal cell wall glycoproteins is a fundamental step in the development of gastric ulceration. A model for gastric lesions is proposed and discussed in the light of the results obtained."} {"id": "PMID:155953", "title": "Characterization of an endogenous transcription inhibitor from Physarum polycephalum.", "content": "A substance has been purified from isolated nuclei of Physarum polycephalum by equilibrium and velocity gradient centrifugations, ion exchange chromatography and gel filtration which has a high molecular weight, can be labeled in vivo with 32P, is heat stable and resistant to amylases, proteases, nucleases and phosphodiesterase but is sensitive to phosphatases or hydrolysis. This material consists of phosphate and glycerol. It selectively inhibits in vitro transcription of RNA polymerases, predominantly the homologous enzyme A by binding to the enzyme. In the presence of this inhibitor of transcription a stable RNA polymerase-template complex cannot be formed. Binding to and inactivation of RNA polymerase is reversible at high ionic strength.", "contents": "Characterization of an endogenous transcription inhibitor from Physarum polycephalum. A substance has been purified from isolated nuclei of Physarum polycephalum by equilibrium and velocity gradient centrifugations, ion exchange chromatography and gel filtration which has a high molecular weight, can be labeled in vivo with 32P, is heat stable and resistant to amylases, proteases, nucleases and phosphodiesterase but is sensitive to phosphatases or hydrolysis. This material consists of phosphate and glycerol. It selectively inhibits in vitro transcription of RNA polymerases, predominantly the homologous enzyme A by binding to the enzyme. In the presence of this inhibitor of transcription a stable RNA polymerase-template complex cannot be formed. Binding to and inactivation of RNA polymerase is reversible at high ionic strength."} {"id": "PMID:155952", "title": "The role of acidic proteins from cytoplasmic fractions of Krebs II ascites cells for efficient translation.", "content": "Acidic proteins with affinity to RNA from cytoplasmic fraction of Krebs II Ascites cells were isolated by means of affinity chromatography on RNA-Sepharose CN-Br-columns. Stepwise elution with 350 mM [K+] and 1000 mM [K+] removed two fractions of proteins both of which are required for the formation of 40S- or 80S-initiation complexes and for efficient translation.", "contents": "The role of acidic proteins from cytoplasmic fractions of Krebs II ascites cells for efficient translation. Acidic proteins with affinity to RNA from cytoplasmic fraction of Krebs II Ascites cells were isolated by means of affinity chromatography on RNA-Sepharose CN-Br-columns. Stepwise elution with 350 mM [K+] and 1000 mM [K+] removed two fractions of proteins both of which are required for the formation of 40S- or 80S-initiation complexes and for efficient translation."} {"id": "PMID:155958", "title": "[Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)].", "content": "A 34 year old white male patient suffering from seropositive \"probable\" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula.", "contents": "[Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)]. A 34 year old white male patient suffering from seropositive \"probable\" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula."} {"id": "PMID:155964", "title": "[Enterococcal flora of some species of synanthropic flies].", "content": "The study of enterococcal species present in 16 species of synanthropic flies revealed the predominance of Str. faecalis and its variants, a high percentage of fly populations being infected. The spectrum of enterococci was proved to depend on the living conditions of the flies. The percentage of Musca domestica with the infected digestive tract was found to vary with changes in the age composition of the fly population.", "contents": "[Enterococcal flora of some species of synanthropic flies]. The study of enterococcal species present in 16 species of synanthropic flies revealed the predominance of Str. faecalis and its variants, a high percentage of fly populations being infected. The spectrum of enterococci was proved to depend on the living conditions of the flies. The percentage of Musca domestica with the infected digestive tract was found to vary with changes in the age composition of the fly population."} {"id": "PMID:155965", "title": "[Dynamics of the types of carrier state and their relationship to the phage group characteristics of pathogenic staphylococci].", "content": "A total of 305 persons belonging to the medical staff of a hospital surgery unit were subjected to multiple examinations during period of up to 8 years. 2,354 staphylococcal strains isolated from these subjects were studied, and the following types of carrier state were determined: constant (23.6 +/- 2.43%), intermittent (57.4 +/- 2.83%), resident (7.9 +/- 1.54%), and the stable absence of carrier state (11.1 +/- 1.60%). An increase in the number of examinations and the terms of observation resulted in a regular increase in the number of intermittent carriers at the expense of constant carriers and persons not identified as carriers. Against this background resident carriers constituted a relatively more stable group. Carrier states of the resident type were connected with staphyloccci belonging to various phage groups without pronounced differences in the frequency with which any of the phage groups occurred.", "contents": "[Dynamics of the types of carrier state and their relationship to the phage group characteristics of pathogenic staphylococci]. A total of 305 persons belonging to the medical staff of a hospital surgery unit were subjected to multiple examinations during period of up to 8 years. 2,354 staphylococcal strains isolated from these subjects were studied, and the following types of carrier state were determined: constant (23.6 +/- 2.43%), intermittent (57.4 +/- 2.83%), resident (7.9 +/- 1.54%), and the stable absence of carrier state (11.1 +/- 1.60%). An increase in the number of examinations and the terms of observation resulted in a regular increase in the number of intermittent carriers at the expense of constant carriers and persons not identified as carriers. Against this background resident carriers constituted a relatively more stable group. Carrier states of the resident type were connected with staphyloccci belonging to various phage groups without pronounced differences in the frequency with which any of the phage groups occurred."} {"id": "PMID:155968", "title": "Assessment of left ventricular filling by echocardiography in normal subjects and in subjects with coronary artery disease and with asymmetric septal hypertrophy.", "content": "To examine the time course of left ventricular filling, a computerized analysis of echocardiograms was performed in 16 normal subjects, 10 patients with coronary artery disease (CAD) but no cardiac enlargement and 7 patients with asymmetric septal hypertrophy (ASH). After hand-controlled digitization of the echocardiogram, a plot of the left ventricular diameter time-curve demonstrated separate phases of rapid filling, slow filling and atrial contribution. The left ventricular diameter at end-systole and at the end of the three diastolic phases was determined by pattern analysis of the diameter-time curve. On analysis of successive beats in the normals, the coefficient of variation for each of these four values of the left ventricular diameter was less than +/- 5%. Between CAD, ASH and normals there was no significant difference in left ventricular end-diastolic diameter, nor in the extent and percentage of diameter shortening during systole. In contrast, abnormalities of the filling pattern were found in CAD and ASH. The maximal rate of diameter lengthening was not different in CAD (13.0 vs 13.7 cm/sec in normals, N.S.) but decreased in ASH (9.3 cm/sec, p less than .01). The percentage of diameter lengthening occurring in the rapid filling phase was decreased in both patient groups (55% in CAD and ASH vs 73% in normals, p less than .001). The slow filling phase did not contribute to more diameter lengthening (13% in CAD and 17% in ASH vs 12% in normals, N.S.). In CAD and ASH, the atrial contribution was markedly increased (33% in CAD and 28% in ASH, vs 15% in normals, p less than .001), and there was a higher rate of diameter lengthening during the atrial contraction (7.6 cm/sec in CAD, p less than .001 and 5.7 cm/sec in ASH, p less than .01, vs 3.1 cm/sec in normals). In conclusion, after computer processing, noninvasive measurements of the left ventricular diameter allows to identify a typical filling pattern in patients with CAD and ASH, consistent with an abnormal compliance of the left ventricle and a compensatory increased atrial contribution.", "contents": "Assessment of left ventricular filling by echocardiography in normal subjects and in subjects with coronary artery disease and with asymmetric septal hypertrophy. To examine the time course of left ventricular filling, a computerized analysis of echocardiograms was performed in 16 normal subjects, 10 patients with coronary artery disease (CAD) but no cardiac enlargement and 7 patients with asymmetric septal hypertrophy (ASH). After hand-controlled digitization of the echocardiogram, a plot of the left ventricular diameter time-curve demonstrated separate phases of rapid filling, slow filling and atrial contribution. The left ventricular diameter at end-systole and at the end of the three diastolic phases was determined by pattern analysis of the diameter-time curve. On analysis of successive beats in the normals, the coefficient of variation for each of these four values of the left ventricular diameter was less than +/- 5%. Between CAD, ASH and normals there was no significant difference in left ventricular end-diastolic diameter, nor in the extent and percentage of diameter shortening during systole. In contrast, abnormalities of the filling pattern were found in CAD and ASH. The maximal rate of diameter lengthening was not different in CAD (13.0 vs 13.7 cm/sec in normals, N.S.) but decreased in ASH (9.3 cm/sec, p less than .01). The percentage of diameter lengthening occurring in the rapid filling phase was decreased in both patient groups (55% in CAD and ASH vs 73% in normals, p less than .001). The slow filling phase did not contribute to more diameter lengthening (13% in CAD and 17% in ASH vs 12% in normals, N.S.). In CAD and ASH, the atrial contribution was markedly increased (33% in CAD and 28% in ASH, vs 15% in normals, p less than .001), and there was a higher rate of diameter lengthening during the atrial contraction (7.6 cm/sec in CAD, p less than .001 and 5.7 cm/sec in ASH, p less than .01, vs 3.1 cm/sec in normals). In conclusion, after computer processing, noninvasive measurements of the left ventricular diameter allows to identify a typical filling pattern in patients with CAD and ASH, consistent with an abnormal compliance of the left ventricle and a compensatory increased atrial contribution."} {"id": "PMID:155969", "title": "Double trisomy as a mosaic. Case history (48, XYY, + 21/47,XY, +21) and survey of the literature of mixed autosomal-gonosomal trisomies.", "content": "The case of a boy is reported showing the typical symptoms of Down's syndrome, in whom the chromosome analysis revealed a mosaic karyotype: 50% 48,XYY,+21/50% 47,XY,+21. Findings of 92 cases from the literature are summarized to show the frequencies of double gonosome-autosome aneuploidies compared with single trisomies. Referring to the different chromosomes involved, the aneuploid cell formation, the frequencies of combinations, as well as the tendency to mosaic formation are analyzed. The age of parents at the time of birth and the life expectancy are described as well as the clinical symptoms. Theories concerning the origin of double aneuploidies are discussed.", "contents": "Double trisomy as a mosaic. Case history (48, XYY, + 21/47,XY, +21) and survey of the literature of mixed autosomal-gonosomal trisomies. The case of a boy is reported showing the typical symptoms of Down's syndrome, in whom the chromosome analysis revealed a mosaic karyotype: 50% 48,XYY,+21/50% 47,XY,+21. Findings of 92 cases from the literature are summarized to show the frequencies of double gonosome-autosome aneuploidies compared with single trisomies. Referring to the different chromosomes involved, the aneuploid cell formation, the frequencies of combinations, as well as the tendency to mosaic formation are analyzed. The age of parents at the time of birth and the life expectancy are described as well as the clinical symptoms. Theories concerning the origin of double aneuploidies are discussed."} {"id": "PMID:155972", "title": "Evidence for a rat granulocyte chalone effect on the proliferation of normal human bone marrow and of myeloid leukemias.", "content": "Evidence is presented that rat ascites cell extracts, acting as granulocyte chalone, temporarily inhibit the cell doubling of granulocytopoietic precursors in suspension cultures of human bone marrow. The extracts do not affect the proliferation of erythroblasts and do not show any cytotoxicity. In addition, a relative increase of granulocytic precursors capable of proliferation was found, suggesting an increase in the resting population of the granulocytopoietic proliferation pool due to extract treatment. However, the extract capable of depressing the proliferation of the normal granulocytopoiesis did not affect the granulocytopoiesis of 7 chronic myeloid and 2 chronic myelomonocytic leukemias at the same dose level. In contrast to these chronic leukemias, blast proliferation of 4 acute myeloid and monocytic leukemias was greatly depressed not only for 6 h but for the whole culture period of 48 h.", "contents": "Evidence for a rat granulocyte chalone effect on the proliferation of normal human bone marrow and of myeloid leukemias. Evidence is presented that rat ascites cell extracts, acting as granulocyte chalone, temporarily inhibit the cell doubling of granulocytopoietic precursors in suspension cultures of human bone marrow. The extracts do not affect the proliferation of erythroblasts and do not show any cytotoxicity. In addition, a relative increase of granulocytic precursors capable of proliferation was found, suggesting an increase in the resting population of the granulocytopoietic proliferation pool due to extract treatment. However, the extract capable of depressing the proliferation of the normal granulocytopoiesis did not affect the granulocytopoiesis of 7 chronic myeloid and 2 chronic myelomonocytic leukemias at the same dose level. In contrast to these chronic leukemias, blast proliferation of 4 acute myeloid and monocytic leukemias was greatly depressed not only for 6 h but for the whole culture period of 48 h."} {"id": "PMID:155973", "title": "Method for continuous measurement of carbon dioxide output during anesthesia. An assessment.", "content": "Employing the Mapleson D circuit, a modified closed-circuit flow-through technique for the continuous measurement of carbon dioxide production (VCO2) was tested for accuracy and precision in a lung model. The recovery of carbon dioxide production was found to be between 90 and 110%, the maximized errors for a single estimate of carbon dioxide production were between +/- 4 and +/- 28%, with the highest errors at high gas flows and low carbon dioxide inputs. Accepting arbitrarily chosen limits of maximized errors of +/- 10%, it could be shown that the system did not work acceptably when the mean carbon dioxide concentration was below 1.5 vol.% within the fresh gas flow rates (2.2--7.7 1 min-1) and the range of minute ventilation (4--10 1 min-1) employed. The half-life of carbon dioxide washout varied between 41 and 138 s, thus limiting the suitability of the system for detecting changes in carbon dioxide output. The method may be used as an approximate monitor of VCO2 in anaesthetized patients, but cannot be regarded as sufficient for research purposes.", "contents": "Method for continuous measurement of carbon dioxide output during anesthesia. An assessment. Employing the Mapleson D circuit, a modified closed-circuit flow-through technique for the continuous measurement of carbon dioxide production (VCO2) was tested for accuracy and precision in a lung model. The recovery of carbon dioxide production was found to be between 90 and 110%, the maximized errors for a single estimate of carbon dioxide production were between +/- 4 and +/- 28%, with the highest errors at high gas flows and low carbon dioxide inputs. Accepting arbitrarily chosen limits of maximized errors of +/- 10%, it could be shown that the system did not work acceptably when the mean carbon dioxide concentration was below 1.5 vol.% within the fresh gas flow rates (2.2--7.7 1 min-1) and the range of minute ventilation (4--10 1 min-1) employed. The half-life of carbon dioxide washout varied between 41 and 138 s, thus limiting the suitability of the system for detecting changes in carbon dioxide output. The method may be used as an approximate monitor of VCO2 in anaesthetized patients, but cannot be regarded as sufficient for research purposes."} {"id": "PMID:155974", "title": "Monitoring ventilation during anesthesia.", "content": "In patients under anesthesia, ventilation is often monitored less adequately than circulation. A simple method, neglected in adults, is the use of a precordial or oesophageal stethoscope. Respiratory volumes may be measured directly, or inferred from flowrates or pressure changes. A rough measurement of inspired volumes may be made using a nonrebreathing valve, and controlling fresh gas input to maintain a constant underfilled reservoir bag. Spirometry of expired volumes is difficult and requires sophisticated apparatus. Respiratory volumes are easily inferred from flowrates using the Wright or Dr\u00e4ger respirometers. Flowrates may also be inferred from pressure changes, which are easy to record, as in the pneumotachorgraph. Accurate measurements require attention to many details, such as linearity of the transducer response over the flowrates measured. Calibration should be with the anesthetic gases used, at controlled temperature and humidity. Positive pressure ventilation peaks give a high flow artefact, and electronic drift requires regular recalibration. Electrical impedance changes may also be used to infer and record respiratory volumes, with reasonable accuracy if individual calibration is carried out. Anesthesia offers excellent opportunities to measure compliance and resistance, but itself changes these values, so that relation to normal values or changes due to pathology is difficult. Occlusion pressure is also readily measured during anesthesia, as an indication of respiratory drive, but rigid control of all other factors affecting respiratory muscle tensions is necessary.", "contents": "Monitoring ventilation during anesthesia. In patients under anesthesia, ventilation is often monitored less adequately than circulation. A simple method, neglected in adults, is the use of a precordial or oesophageal stethoscope. Respiratory volumes may be measured directly, or inferred from flowrates or pressure changes. A rough measurement of inspired volumes may be made using a nonrebreathing valve, and controlling fresh gas input to maintain a constant underfilled reservoir bag. Spirometry of expired volumes is difficult and requires sophisticated apparatus. Respiratory volumes are easily inferred from flowrates using the Wright or Dr\u00e4ger respirometers. Flowrates may also be inferred from pressure changes, which are easy to record, as in the pneumotachorgraph. Accurate measurements require attention to many details, such as linearity of the transducer response over the flowrates measured. Calibration should be with the anesthetic gases used, at controlled temperature and humidity. Positive pressure ventilation peaks give a high flow artefact, and electronic drift requires regular recalibration. Electrical impedance changes may also be used to infer and record respiratory volumes, with reasonable accuracy if individual calibration is carried out. Anesthesia offers excellent opportunities to measure compliance and resistance, but itself changes these values, so that relation to normal values or changes due to pathology is difficult. Occlusion pressure is also readily measured during anesthesia, as an indication of respiratory drive, but rigid control of all other factors affecting respiratory muscle tensions is necessary."} {"id": "PMID:155976", "title": "The Coffin-Siris syndrome.", "content": "A 14-month-old female with the Coffin-Siris syndrome is described. Typical features included underweight at birth, growth retardation, microcephaly, profound mental retardation, severe hypotonia with lax joints, feeding difficulties and frequent respiratory tract infections; sparce scalp hair, small nose, epicanthic folds, a prominent philtrum and full lips; a congenital heart defect; hypoplasia or aplasia of the distal phalanges of digits 2--5 and the corresponding nails, especially of the fifth fingers and toes, and aplasia of the middle phalanges of the little fingers and the second and fifth toes; severe delay in bone maturation. The proposita also showed hypoplasia of the lateral portions of both clavicles. Inheritance of the Coffin-Siris syndrome is possibly autosomal recessive.", "contents": "The Coffin-Siris syndrome. A 14-month-old female with the Coffin-Siris syndrome is described. Typical features included underweight at birth, growth retardation, microcephaly, profound mental retardation, severe hypotonia with lax joints, feeding difficulties and frequent respiratory tract infections; sparce scalp hair, small nose, epicanthic folds, a prominent philtrum and full lips; a congenital heart defect; hypoplasia or aplasia of the distal phalanges of digits 2--5 and the corresponding nails, especially of the fifth fingers and toes, and aplasia of the middle phalanges of the little fingers and the second and fifth toes; severe delay in bone maturation. The proposita also showed hypoplasia of the lateral portions of both clavicles. Inheritance of the Coffin-Siris syndrome is possibly autosomal recessive."} {"id": "PMID:155977", "title": "Mechanism of cell dissociation with trypsin and EDTA.", "content": "The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment.", "contents": "Mechanism of cell dissociation with trypsin and EDTA. The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment."} {"id": "PMID:155978", "title": "Heterotransplantation of human leukemic B-cell, T-cell and null-cell lines in hamsters.", "content": "Human leukemic B-cell (BALL-1), T-cell (TALL-1) and null-cell (NALL-1) lines have been established from three patients with acute lymphoblastic leukemia (ALL). To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7) cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage.", "contents": "Heterotransplantation of human leukemic B-cell, T-cell and null-cell lines in hamsters. Human leukemic B-cell (BALL-1), T-cell (TALL-1) and null-cell (NALL-1) lines have been established from three patients with acute lymphoblastic leukemia (ALL). To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7) cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage."} {"id": "PMID:155975", "title": "Chronic non-allergic hypertrophic rhinitis. A histochemical study.", "content": "The enzymatic changes in chronic hypertrophic rhinitis were studied in 14 patients. The cholinesterase content was increased in the subepithelium and stroma, denoting parasympathetic hyperactivity. Acid phosphatase was increased in the epithelium, subepithelium and around the glands, indicating increased shedding and phagocytic activity. Succinic dehydrogenase, alkaline phosphatase and alpha-esterase were increased in the mucous glands, denoting increase secretory activity, hence increased natural defence mechanism of the nasal mucosa.", "contents": "Chronic non-allergic hypertrophic rhinitis. A histochemical study. The enzymatic changes in chronic hypertrophic rhinitis were studied in 14 patients. The cholinesterase content was increased in the subepithelium and stroma, denoting parasympathetic hyperactivity. Acid phosphatase was increased in the epithelium, subepithelium and around the glands, indicating increased shedding and phagocytic activity. Succinic dehydrogenase, alkaline phosphatase and alpha-esterase were increased in the mucous glands, denoting increase secretory activity, hence increased natural defence mechanism of the nasal mucosa."} {"id": "PMID:155980", "title": "Immunotherapy of gastrointestinal cancer patients with levamisole.", "content": "Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.", "contents": "Immunotherapy of gastrointestinal cancer patients with levamisole. Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method."} {"id": "PMID:155981", "title": "Recurrent transient thyrotoxicosis with painless thyroiditis--a case report.", "content": "A case of a 40-year-old woman who was suffering from painless thyroiditis with recurrent transient thyrotoxicosis is reported. Acute exacerbations occurred four times during the past ten years, two after delivery and two after catching a cold. Serum thyroid hormones increased, though radioiodine uptake by the thyroid was very low and no inflammatory signs were observed. The histological findings of the thyroid were of atypical thyroiditis and not consistent with either chronic lymphocytic thyroiditis or subacute thyroiditis. Tanned sheep red cell hemagglutination titers for anti-thyroglobulin antibodies (TRC) and for anti-microsomal antibodies (MHA) were negative or low. The disease seems to be rare and the pathophysiology and etiology are discussed.", "contents": "Recurrent transient thyrotoxicosis with painless thyroiditis--a case report. A case of a 40-year-old woman who was suffering from painless thyroiditis with recurrent transient thyrotoxicosis is reported. Acute exacerbations occurred four times during the past ten years, two after delivery and two after catching a cold. Serum thyroid hormones increased, though radioiodine uptake by the thyroid was very low and no inflammatory signs were observed. The histological findings of the thyroid were of atypical thyroiditis and not consistent with either chronic lymphocytic thyroiditis or subacute thyroiditis. Tanned sheep red cell hemagglutination titers for anti-thyroglobulin antibodies (TRC) and for anti-microsomal antibodies (MHA) were negative or low. The disease seems to be rare and the pathophysiology and etiology are discussed."} {"id": "PMID:155982", "title": "Three cases of myxofibroma.", "content": "Myxofibroma is a rare tumor. Three cases of myxofibroma, each of which developed at the right mandibular ramus, mandibular anterior tooth region, are presented. Myxofibroma developing in the mandibular ramus region is rare, and there has been only one case reported so far in Japan.", "contents": "Three cases of myxofibroma. Myxofibroma is a rare tumor. Three cases of myxofibroma, each of which developed at the right mandibular ramus, mandibular anterior tooth region, are presented. Myxofibroma developing in the mandibular ramus region is rare, and there has been only one case reported so far in Japan."} {"id": "PMID:155983", "title": "Technical considerations in the evaluation of pediatric motor scales.", "content": "Guidelines are suggested for evaluating the validity and reliability of fine and gross motor scales. In the process of examining three types of validity (domain, construct, discriminant) and two types of reliability (interobserver, decision-making), it was found that there were marked deficiencies in most of the instruments currently available, particularly in the areas of discriminant validity and decision-making reliability. Each psychometric property of the scales was addressed from both scale-developer and user perspectives. An evaluative checklist is generated to assist occupational therapists who need to decide on the quality and appropriateness of a motor behavior scale for specific decision applications.", "contents": "Technical considerations in the evaluation of pediatric motor scales. Guidelines are suggested for evaluating the validity and reliability of fine and gross motor scales. In the process of examining three types of validity (domain, construct, discriminant) and two types of reliability (interobserver, decision-making), it was found that there were marked deficiencies in most of the instruments currently available, particularly in the areas of discriminant validity and decision-making reliability. Each psychometric property of the scales was addressed from both scale-developer and user perspectives. An evaluative checklist is generated to assist occupational therapists who need to decide on the quality and appropriateness of a motor behavior scale for specific decision applications."} {"id": "PMID:155985", "title": "Clinical evaluation of automated processing of electrocardiograms by the Veterans Administration program (AVA 3.4).", "content": "Automated processing of electrocardiograms by the Veterans Administration program was evaluated for both agreement with physician interpretation and interpretative accuracy as assessed with nonelectrocardiographic criteria. One thousand unselected electrocardiograms were analyzed by two reviewer groups, one familiar and the other unfamiliar with the computer program. A significant number of measurement errors involving repolarization changes and left axis deviation occurred; however, interpretative disagreements related to statistical decision were largely language-related. Use of a printout with a more traditional format resulted in agreement with physician interpretation by both reviewer groups in more than 80 percent of cases. Overall sensitivity based on agreement with nonelectrocardiographic criteria was significantly greater with use of the computer program than with use of the conventional criteria utilized by the reviewers. This difference was particularly evident in the subgroup analysis of myocardial infarction and left ventricular hypertrophy. The degree of overdiagnosis of left ventricular hypertrophy and posteroinferior infarction was initially unacceptable, but this difficulty was corrected by adjustment of probabilities. Clinical acceptability of the Veterans Administration program appears to require greater physician education than that needed for other computer programs of electrocardiographic analysis; the flexibility of interpretation by statistical decision offers the potential for better diagnostic accuracy.", "contents": "Clinical evaluation of automated processing of electrocardiograms by the Veterans Administration program (AVA 3.4). Automated processing of electrocardiograms by the Veterans Administration program was evaluated for both agreement with physician interpretation and interpretative accuracy as assessed with nonelectrocardiographic criteria. One thousand unselected electrocardiograms were analyzed by two reviewer groups, one familiar and the other unfamiliar with the computer program. A significant number of measurement errors involving repolarization changes and left axis deviation occurred; however, interpretative disagreements related to statistical decision were largely language-related. Use of a printout with a more traditional format resulted in agreement with physician interpretation by both reviewer groups in more than 80 percent of cases. Overall sensitivity based on agreement with nonelectrocardiographic criteria was significantly greater with use of the computer program than with use of the conventional criteria utilized by the reviewers. This difference was particularly evident in the subgroup analysis of myocardial infarction and left ventricular hypertrophy. The degree of overdiagnosis of left ventricular hypertrophy and posteroinferior infarction was initially unacceptable, but this difficulty was corrected by adjustment of probabilities. Clinical acceptability of the Veterans Administration program appears to require greater physician education than that needed for other computer programs of electrocardiographic analysis; the flexibility of interpretation by statistical decision offers the potential for better diagnostic accuracy."} {"id": "PMID:155986", "title": "Left ventricular radius to wall thickness ratio.", "content": "Left ventricular relative wall thickness, expressed as the ratio of end-diastolic radius to wall thickness (R/Th ratio), has a constant relation with left ventricular systolic pressure in children and adults with a normal heart, subjects with physiologic forms of cardiac hypertrophy (athletes) and patients with compensated chronic left ventricular volume overload (chronic aortic regurgitation). Greatly increased values for the radius/thickness ratio, suggesting inadequate hypertrophy, indicate a poor prognosis in patients with chronic aortic regurgitation and in those with congestive cardiomyopathy; decreased values for this ratio are found in patients with hypertrophic cardiomyopathy (inappropriate hypertrophy) and in patients with compensated aortic stenosis (appropriate hypertrophy). In patients with compensated aortic stenosis, echocardiographic measurement of the left ventricular end-diastolic radius/wall thickness ratio has been used to estimate left ventricular systolic pressure. Measurement of left ventricular relative wall thickness appears to provide diagnostic and prognostic data in patients with a broad variety of cardiac disorders.", "contents": "Left ventricular radius to wall thickness ratio. Left ventricular relative wall thickness, expressed as the ratio of end-diastolic radius to wall thickness (R/Th ratio), has a constant relation with left ventricular systolic pressure in children and adults with a normal heart, subjects with physiologic forms of cardiac hypertrophy (athletes) and patients with compensated chronic left ventricular volume overload (chronic aortic regurgitation). Greatly increased values for the radius/thickness ratio, suggesting inadequate hypertrophy, indicate a poor prognosis in patients with chronic aortic regurgitation and in those with congestive cardiomyopathy; decreased values for this ratio are found in patients with hypertrophic cardiomyopathy (inappropriate hypertrophy) and in patients with compensated aortic stenosis (appropriate hypertrophy). In patients with compensated aortic stenosis, echocardiographic measurement of the left ventricular end-diastolic radius/wall thickness ratio has been used to estimate left ventricular systolic pressure. Measurement of left ventricular relative wall thickness appears to provide diagnostic and prognostic data in patients with a broad variety of cardiac disorders."} {"id": "PMID:155987", "title": "Fibrinolysis in familial pulmonary hypertension.", "content": "Although an autosomal dominant mode of inheritance has been documented for many cases of primary pulmonary hypertension, the pathogenesis of the disease remains unclear. A report of abnormal fibrinolysis in familial pulmonary hypertension has raised the possibility that the pathogenesis may be related to an impaired ability to lyse recurrent pulmonary microemboli. Primary pulmonary hypertension was diagnosed in three of ten members of a kindred. The pattern of inheritance was compatible with an autosomal dominant gene. Eight members of the kindred were available for study, one of whom has primary pulmonary hypertension. The results of coagulation studies, caseinolytic determinations of plasminogen and antiplasmin, and fibrinolytic titers of antiurokinase did not differ significantly from those of the control group. These findings suggest that a deficient fibrinolytic system is not the cause of primary pulmonary hypertension, although differences in methodology may explain our inability to demonstrate abnormal circulating fibrinolysis in this kindred.", "contents": "Fibrinolysis in familial pulmonary hypertension. Although an autosomal dominant mode of inheritance has been documented for many cases of primary pulmonary hypertension, the pathogenesis of the disease remains unclear. A report of abnormal fibrinolysis in familial pulmonary hypertension has raised the possibility that the pathogenesis may be related to an impaired ability to lyse recurrent pulmonary microemboli. Primary pulmonary hypertension was diagnosed in three of ten members of a kindred. The pattern of inheritance was compatible with an autosomal dominant gene. Eight members of the kindred were available for study, one of whom has primary pulmonary hypertension. The results of coagulation studies, caseinolytic determinations of plasminogen and antiplasmin, and fibrinolytic titers of antiurokinase did not differ significantly from those of the control group. These findings suggest that a deficient fibrinolytic system is not the cause of primary pulmonary hypertension, although differences in methodology may explain our inability to demonstrate abnormal circulating fibrinolysis in this kindred."} {"id": "PMID:155988", "title": "Tetralogy of Fallot in adults. A report on 147 patients.", "content": "Presented here is the clinical and hemodynamic profile of 147 patients, above the age of 18 with tetralogy of Fallot. Cardiac catheterization and selective cineangiocardiography were performed in all. Infundibular pulmonary stenosis, a subaortic large infracristal ventricular septal defect, mitral-aortic fibrous continuity and equal pressures in both the ventricles and aorta were considered mandatory for the diagnosis of tetralogy of Fallot. Cardiac enlargement was seen in 25.8 per cent of the patients, and 15.6 per cent were in congestive cardiac failure; 9.5 per cent had systemic hypertension, and aortic regurgitation was present in 6.7 per cent. A reticular pattern in the lung fields due to bronchial collaterals was seen in 23.1 per cent. The incidence of right aortic arch (19.9 per cent), absent left pulmonary artery (2.8 per cent), absent right pulmonary artery (0.7 per cent) and dextrocardia (1.4 per cent) is brought out. The right atrial mean pressure was increased in 4.8 per cent and a prominent \"a\" wave greater than 10 mm Hg was present in 10.9 per cent. The right ventricular end-diastolic pressure was increased in 23.8 per cent and the left ventricular end-diastolic pressure in 25.9 per cent of the patients.", "contents": "Tetralogy of Fallot in adults. A report on 147 patients. Presented here is the clinical and hemodynamic profile of 147 patients, above the age of 18 with tetralogy of Fallot. Cardiac catheterization and selective cineangiocardiography were performed in all. Infundibular pulmonary stenosis, a subaortic large infracristal ventricular septal defect, mitral-aortic fibrous continuity and equal pressures in both the ventricles and aorta were considered mandatory for the diagnosis of tetralogy of Fallot. Cardiac enlargement was seen in 25.8 per cent of the patients, and 15.6 per cent were in congestive cardiac failure; 9.5 per cent had systemic hypertension, and aortic regurgitation was present in 6.7 per cent. A reticular pattern in the lung fields due to bronchial collaterals was seen in 23.1 per cent. The incidence of right aortic arch (19.9 per cent), absent left pulmonary artery (2.8 per cent), absent right pulmonary artery (0.7 per cent) and dextrocardia (1.4 per cent) is brought out. The right atrial mean pressure was increased in 4.8 per cent and a prominent \"a\" wave greater than 10 mm Hg was present in 10.9 per cent. The right ventricular end-diastolic pressure was increased in 23.8 per cent and the left ventricular end-diastolic pressure in 25.9 per cent of the patients."} {"id": "PMID:155989", "title": "Parental speech to young Down's syndrome children: an intervention study.", "content": "Parents with Down's syndrome children who were at the one-two word stage of expressive language development were given a language objective to work towards with their child, but no instructions on how to attain this goal. The parents spontaneously altered their language strategies in their attempts. Some parents were more successful and differed in their strategies, using more target words in shorter \"statement\" utterances. Parents who used a questioning or imitating strategy were less successful. The less successful parents were then shown how to alter their language strategies more appropriately to produce a greater improvement in their child's use of the target words.", "contents": "Parental speech to young Down's syndrome children: an intervention study. Parents with Down's syndrome children who were at the one-two word stage of expressive language development were given a language objective to work towards with their child, but no instructions on how to attain this goal. The parents spontaneously altered their language strategies in their attempts. Some parents were more successful and differed in their strategies, using more target words in shorter \"statement\" utterances. Parents who used a questioning or imitating strategy were less successful. The less successful parents were then shown how to alter their language strategies more appropriately to produce a greater improvement in their child's use of the target words."} {"id": "PMID:155990", "title": "Use of laparoscopy to determine the microbiologic etiology of acute salpingitis.", "content": "To determine the microbiologic etiology of acute salpingitis, laparoscopy was used in 26 patients to obtain specimens for a variety of microorganisms directly from the fallopian tube. Simultaneous culdocentesis was performed to obtain peritoneal fluid for microbiologic analysis. A variety of microorganisms were isolated from the fallopian tubes and cul-de-sac aspirate. However, the organisms isolated from the fallopian tube were not consistent with the cul-de-sac isolates. It appears that direct culture from the fallopian tube may be necessary to determine the microbiologic etiology and pathogenesis of acute salpingitis. N. gonorrhoeae was isolated from the cul-de-sac in 32 per cent of cases and the fallopian tube in 19 per cent. In patients with endocervical gonorrhea, the gonococcus was isolated from the fallopian tube in 38.5 per cent of cases. Aerobic and/or anaerobic bacteria were present in the cul-de-sac aspirate in 46 per cent of patients and in the fallopian tube in 38 per cent.", "contents": "Use of laparoscopy to determine the microbiologic etiology of acute salpingitis. To determine the microbiologic etiology of acute salpingitis, laparoscopy was used in 26 patients to obtain specimens for a variety of microorganisms directly from the fallopian tube. Simultaneous culdocentesis was performed to obtain peritoneal fluid for microbiologic analysis. A variety of microorganisms were isolated from the fallopian tubes and cul-de-sac aspirate. However, the organisms isolated from the fallopian tube were not consistent with the cul-de-sac isolates. It appears that direct culture from the fallopian tube may be necessary to determine the microbiologic etiology and pathogenesis of acute salpingitis. N. gonorrhoeae was isolated from the cul-de-sac in 32 per cent of cases and the fallopian tube in 19 per cent. In patients with endocervical gonorrhea, the gonococcus was isolated from the fallopian tube in 38.5 per cent of cases. Aerobic and/or anaerobic bacteria were present in the cul-de-sac aspirate in 46 per cent of patients and in the fallopian tube in 38 per cent."} {"id": "PMID:155991", "title": "Cow red blood cells. I. Effect of purines, pyrimidines, and nucleosides in bovine red cell glycolysis.", "content": "Cow red cells, under in vitro incubation conditions, exhibit a comparatively low glycolytic rate of 0.56 +/- 0.05 micromol/(ml cells.h), with a ratio of lactate formed to glucose consumed of 1.58. It has been found that this low glycolytic rate can be stimulated 50--60% above the basal level in the presence of a variety of purine and pyrimidine compounds including adenosine, inosine, adenine, hypoxanthine, xanthine, and uracil. In contrast, calf red cells, which have a much higher glycolytic rate, display no discernible response to these agents. In attempts to elucidate the mechanism by which this stimulation takes place, both glucose transport and glycolytic enzyme activities were determined in the presence of these stimulators. Glucose influx in cow red cells, measured using the glucose analog 3-O-methyl-glucose, exhibits both a low Km of 117 microM and a Vmax of 0.38 micromol/(ml cells.min), and is unaltered in the presence of adenosine. On the other hand, hexokinase, which in normal hemolysates of cow red cells has an activity of 0.49 +/- 0.03 micromol/(g Hb.min). was found to be stimulated to 0.73 micromol/(g Hb.min) in the presence of adenine. Both pyruvate kinase and phosphofructokinase were unaffected by this compound. These data suggest that certain purines and pyrimidine compounds may exert their stimulatory effect on hexokinase activity, resulting in an augmentation of cow red cell glycolysis.", "contents": "Cow red blood cells. I. Effect of purines, pyrimidines, and nucleosides in bovine red cell glycolysis. Cow red cells, under in vitro incubation conditions, exhibit a comparatively low glycolytic rate of 0.56 +/- 0.05 micromol/(ml cells.h), with a ratio of lactate formed to glucose consumed of 1.58. It has been found that this low glycolytic rate can be stimulated 50--60% above the basal level in the presence of a variety of purine and pyrimidine compounds including adenosine, inosine, adenine, hypoxanthine, xanthine, and uracil. In contrast, calf red cells, which have a much higher glycolytic rate, display no discernible response to these agents. In attempts to elucidate the mechanism by which this stimulation takes place, both glucose transport and glycolytic enzyme activities were determined in the presence of these stimulators. Glucose influx in cow red cells, measured using the glucose analog 3-O-methyl-glucose, exhibits both a low Km of 117 microM and a Vmax of 0.38 micromol/(ml cells.min), and is unaltered in the presence of adenosine. On the other hand, hexokinase, which in normal hemolysates of cow red cells has an activity of 0.49 +/- 0.03 micromol/(g Hb.min). was found to be stimulated to 0.73 micromol/(g Hb.min) in the presence of adenine. Both pyruvate kinase and phosphofructokinase were unaffected by this compound. These data suggest that certain purines and pyrimidine compounds may exert their stimulatory effect on hexokinase activity, resulting in an augmentation of cow red cell glycolysis."} {"id": "PMID:155992", "title": "Cardiac changes during behavioral stress in dogs.", "content": "Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes.", "contents": "Cardiac changes during behavioral stress in dogs. Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes."} {"id": "PMID:155993", "title": "Effect of brain 5-hydroxytryptamine alterations on reflex bradycardia in rats.", "content": "The vasopressor and bradycardia responses to an intravenous dose of epinephrine were assessed in saline-controlled, 5-hydroxytryptamine-(5-HT) depleted, and 5-HT-potentiated rats. Regardless of the previous treatment epinephrine produced an insignificant change in the basal levels of mean arterial pressure and heart rate. However, brain serotonin alteration did produce some influences on the reflex bradycardia in response to an elevation in arterial pressure. Elevating 5-HT contents in brain with 5-hydroxytryptophan (5-HTP) after peripheral decarboxylase inhibition with Ro 4-4602 produced a significant reduction in reflex bradycardia compared to the controls. In contrast, depleting 5-HT contents in brain with either p-chlorophenylalanine (PCPA) or 5,7-dihydroxytryptamine (5,7-DHT) led to an enhancement of epinephrine-induced bradycardia. Moreover, the enhanced reflex bradycardia induced by PCPA treatment was readily blocked by the replacement of the depleted brain 5-HT with 5-HTP and Ro 4-4602. The results suggest that serotoninergic systems play a role in the elaboration or modulation of reflex bradycardia. Specifically, 5-HT appears to inhibit reflex bradycardia since its depletion facilitated and its elevation inhibited reflex bradycardia.", "contents": "Effect of brain 5-hydroxytryptamine alterations on reflex bradycardia in rats. The vasopressor and bradycardia responses to an intravenous dose of epinephrine were assessed in saline-controlled, 5-hydroxytryptamine-(5-HT) depleted, and 5-HT-potentiated rats. Regardless of the previous treatment epinephrine produced an insignificant change in the basal levels of mean arterial pressure and heart rate. However, brain serotonin alteration did produce some influences on the reflex bradycardia in response to an elevation in arterial pressure. Elevating 5-HT contents in brain with 5-hydroxytryptophan (5-HTP) after peripheral decarboxylase inhibition with Ro 4-4602 produced a significant reduction in reflex bradycardia compared to the controls. In contrast, depleting 5-HT contents in brain with either p-chlorophenylalanine (PCPA) or 5,7-dihydroxytryptamine (5,7-DHT) led to an enhancement of epinephrine-induced bradycardia. Moreover, the enhanced reflex bradycardia induced by PCPA treatment was readily blocked by the replacement of the depleted brain 5-HT with 5-HTP and Ro 4-4602. The results suggest that serotoninergic systems play a role in the elaboration or modulation of reflex bradycardia. Specifically, 5-HT appears to inhibit reflex bradycardia since its depletion facilitated and its elevation inhibited reflex bradycardia."} {"id": "PMID:155994", "title": "Diabetes, dietary tryptophan, and protein intake regulation in weanling rats.", "content": "The effects of streptozotocin-induced diabetes and tryptophan content of the protein fed on protein intake regulation by weanling rats selecting from 10 and 60% casein diets were evaluated. In uncompensated diabetes the ratio of tryptophan to other selected neutral amino acids in plasma and brain tryptophan were reduced, protein intake per unit of body weight was increased, and serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were unaffected. Enrichment of the tryptophan content of the ingested protein caused a decrease in protein, but not energy consumption of both diabetic and nondiabetic rats. The reduction in protein intake correlated inversely with increases in the tryptophan content relative to the neutral amino acids in plasma and with increases in brain tryptophan and serotonin levels in both diabetic and nondiabetic rats. The data suggest that protein-feeding behavior is regulated by a mechanism that includes brain serotonergic activity with insulin, through its influence on circulating amino acids, determining the quantity of protein consumed in relation to body weight.", "contents": "Diabetes, dietary tryptophan, and protein intake regulation in weanling rats. The effects of streptozotocin-induced diabetes and tryptophan content of the protein fed on protein intake regulation by weanling rats selecting from 10 and 60% casein diets were evaluated. In uncompensated diabetes the ratio of tryptophan to other selected neutral amino acids in plasma and brain tryptophan were reduced, protein intake per unit of body weight was increased, and serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were unaffected. Enrichment of the tryptophan content of the ingested protein caused a decrease in protein, but not energy consumption of both diabetic and nondiabetic rats. The reduction in protein intake correlated inversely with increases in the tryptophan content relative to the neutral amino acids in plasma and with increases in brain tryptophan and serotonin levels in both diabetic and nondiabetic rats. The data suggest that protein-feeding behavior is regulated by a mechanism that includes brain serotonergic activity with insulin, through its influence on circulating amino acids, determining the quantity of protein consumed in relation to body weight."} {"id": "PMID:155997", "title": "Post-weaning heart development and dietary lipid level in the male rat: evolution of lipoprotein lipase activity.", "content": "The wet weight evolution and specific and total lipoprotein lipase (LPL) activities of the heart were studied in male rats fed with diets containing 4, 12 or 21 p. 100 lipids from 50 g (3 weeks age) to 400 g body weight (13 weeks of age). The animals were compared at 100, 150, 200 and 400 g. The main results show that:--a lipid-rich diet caused some cardiac hypertrophy beginning at 100 g body weight:--specific LPL activity (activity/g of wet tissue) in the 50-400 g interval was higher when the diet contained more lipids;--when the diet contained 4 p. 100 and 12 p. 100 lipids, specific LPL activity decreased from weaning until a plateau was reached at 200 g body weight. On the other hand, when the diet contained 21 p. 100 lipids, specific LPL activity increased to a maximum in the 150-200 g interval; it then declined rapidly so that at 400 g there were no longer significant differences between the specific LPL cardiac activities of the three groups of animals. The activities thus became independant of the dietary lipid level;--total LPL cardiac activity was higher when the diet contained more lipids, at least up to the 400 g stage. When the diet contained 4 and 12 p. 100 lipids, the activity increased linearly in the 100-400 g interval. When the diet contained 21 p. 100 lipids, it increased very rapidly in the 50-200 g interval then decreased in the 200-400 g interval. In the latter interval, the differences between LPL activities of the three groups were less so that at 400 g there was only significant difference between the extreme high and low lipid groups. Thus, as specific activity, total LPL cardiac activity tended to become independent of dietary lipid level when the animals became adult.", "contents": "Post-weaning heart development and dietary lipid level in the male rat: evolution of lipoprotein lipase activity. The wet weight evolution and specific and total lipoprotein lipase (LPL) activities of the heart were studied in male rats fed with diets containing 4, 12 or 21 p. 100 lipids from 50 g (3 weeks age) to 400 g body weight (13 weeks of age). The animals were compared at 100, 150, 200 and 400 g. The main results show that:--a lipid-rich diet caused some cardiac hypertrophy beginning at 100 g body weight:--specific LPL activity (activity/g of wet tissue) in the 50-400 g interval was higher when the diet contained more lipids;--when the diet contained 4 p. 100 and 12 p. 100 lipids, specific LPL activity decreased from weaning until a plateau was reached at 200 g body weight. On the other hand, when the diet contained 21 p. 100 lipids, specific LPL activity increased to a maximum in the 150-200 g interval; it then declined rapidly so that at 400 g there were no longer significant differences between the specific LPL cardiac activities of the three groups of animals. The activities thus became independant of the dietary lipid level;--total LPL cardiac activity was higher when the diet contained more lipids, at least up to the 400 g stage. When the diet contained 4 and 12 p. 100 lipids, the activity increased linearly in the 100-400 g interval. When the diet contained 21 p. 100 lipids, it increased very rapidly in the 50-200 g interval then decreased in the 200-400 g interval. In the latter interval, the differences between LPL activities of the three groups were less so that at 400 g there was only significant difference between the extreme high and low lipid groups. Thus, as specific activity, total LPL cardiac activity tended to become independent of dietary lipid level when the animals became adult."} {"id": "PMID:156000", "title": "Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia.", "content": "A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden-Spatz disease, and lipofuscinosis. In these conditions, with the exception of Hallervorden-Spatz disease neurofibrillary changes were previously recognized but paired helical filaments were identified only in some cases. Moreover, in the present series, the age of patients at death was often younger than in previously recorded cases.", "contents": "Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden-Spatz disease, and lipofuscinosis. In these conditions, with the exception of Hallervorden-Spatz disease neurofibrillary changes were previously recognized but paired helical filaments were identified only in some cases. Moreover, in the present series, the age of patients at death was often younger than in previously recorded cases."} {"id": "PMID:156002", "title": "[Experimental study of the effectiveness of antibacterial preparations in treating dysentery].", "content": "It was found that for successful elaboration of effective schemes for the use of antibacterial drugs in treatment of dysentery it was necessary to exploit various experimental models providing consideration of the drug toxicity and effect on the extra- and intracellular growth of the bacteria in addition to the other factors. The administration of enteroceptol for 3 days followed by furazolidon showed the best therapeutic effect in the treatment of guinea pigs with Shigella keratoconjunctivitis and Syrian hamsters with dysentery. The above drugs had low toxicity which was shown in the experiments with Hep-2 cell cultures. It was concluded that the use of the drugs with different modes of action was advisable in treatment of dysentery.", "contents": "[Experimental study of the effectiveness of antibacterial preparations in treating dysentery]. It was found that for successful elaboration of effective schemes for the use of antibacterial drugs in treatment of dysentery it was necessary to exploit various experimental models providing consideration of the drug toxicity and effect on the extra- and intracellular growth of the bacteria in addition to the other factors. The administration of enteroceptol for 3 days followed by furazolidon showed the best therapeutic effect in the treatment of guinea pigs with Shigella keratoconjunctivitis and Syrian hamsters with dysentery. The above drugs had low toxicity which was shown in the experiments with Hep-2 cell cultures. It was concluded that the use of the drugs with different modes of action was advisable in treatment of dysentery."} {"id": "PMID:155999", "title": "[Effects of prolactin on nucleo-proteic metabolism in gill epithelium of two euryhalin mullets, Chelon labrosus and Liza ramada during fresh-water adaptation (author's transL)].", "content": "Prolactin (PRL) treatment induced a decrease in DNA content in SW, -- an increase in FW 8 days, -- and no effect in FW 20 days fish. In \"nuclear\", \"microsomal\" and \"supernatant\" centrifugation fractions, RNA content was increased in SW, -- decreased in FW 8 days, by PRL treatment while a little increase was observed in FW 20 days fish with an increase of 14C leucine and 3H uridine incorporation. These results are discussed with reference to existence of two chloride-cell-types.", "contents": "[Effects of prolactin on nucleo-proteic metabolism in gill epithelium of two euryhalin mullets, Chelon labrosus and Liza ramada during fresh-water adaptation (author's transL)]. Prolactin (PRL) treatment induced a decrease in DNA content in SW, -- an increase in FW 8 days, -- and no effect in FW 20 days fish. In \"nuclear\", \"microsomal\" and \"supernatant\" centrifugation fractions, RNA content was increased in SW, -- decreased in FW 8 days, by PRL treatment while a little increase was observed in FW 20 days fish with an increase of 14C leucine and 3H uridine incorporation. These results are discussed with reference to existence of two chloride-cell-types."} {"id": "PMID:156006", "title": "An acne grading method using photographic standards.", "content": "A grading system for following the clinical course of acne was devised in which overall severity of acne is evaluated on a zero to eight scale anchored to photographic standards that illustrate grades 0, 2, 4, 6, and 8. Experience with use of this system in large-scale clinical trials has shown it to be useful and reliable. Photographs taken at each visit create a permanent and regradable record of each subject's clinical status throughout the course of treatment.", "contents": "An acne grading method using photographic standards. A grading system for following the clinical course of acne was devised in which overall severity of acne is evaluated on a zero to eight scale anchored to photographic standards that illustrate grades 0, 2, 4, 6, and 8. Experience with use of this system in large-scale clinical trials has shown it to be useful and reliable. Photographs taken at each visit create a permanent and regradable record of each subject's clinical status throughout the course of treatment."} {"id": "PMID:156011", "title": "Complicated intestinal atresias.", "content": "In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction.", "contents": "Complicated intestinal atresias. In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction."} {"id": "PMID:156014", "title": "[Gastroschisis: study of a series of 50 cases from 1960 to 1976 and therapeutic indications].", "content": "Fifty cases of gastroschisis were treated at the H\u00f4pital des Enfants Malades from 1960 to 1976. Up to 1973, 90% of the babies died. From 1974-1976, 17 infants were treated and 10 (59%) were cured. The authors emphasise the importance of intravenous feeding, the prevention of infections and intensive respiratory care. Complete intestinal ileus for more than one month is associated with a bad prognosis. The use of drugs and further surgery in this situation in discussed.", "contents": "[Gastroschisis: study of a series of 50 cases from 1960 to 1976 and therapeutic indications]. Fifty cases of gastroschisis were treated at the H\u00f4pital des Enfants Malades from 1960 to 1976. Up to 1973, 90% of the babies died. From 1974-1976, 17 infants were treated and 10 (59%) were cured. The authors emphasise the importance of intravenous feeding, the prevention of infections and intensive respiratory care. Complete intestinal ileus for more than one month is associated with a bad prognosis. The use of drugs and further surgery in this situation in discussed."} {"id": "PMID:156015", "title": "[Development of neuromuscular spindles in the muscles of the floor of the human oral cavity during intrauterine development].", "content": "By means of histological, neurohistological, histochemical and morphometrical techniques the development, number and histotopography of neuromuscular spindles have been studied in 860 muscles of the mouth cavity fundus obtained from 108 human embryos, fetuses and newborns. In genioglossal and in geniohyoid muscles, the spindles are layed down at the 7th week of gestation. Their differentiation starts at the 9th week -- with forming the first sensitive endings, nuclear bursa and cellular elements of the spindle capsule. By the 14th week, the subcapsular space becomes evident, and by the 20th week of embryogenesis neuromuscular spindles resemble definitive structures. In the anterior belly of the digastric muscle, the foundation and initial differentiation of the spindles is retarded. The mylohyoid muscle has no spindles. Morphogenesis of neuromuscular spindles has been studied with special reference to the beginning of functional activity of the fundal muscles in the mouth cavity during embryogenesis in view of the theory of systemogenesis.", "contents": "[Development of neuromuscular spindles in the muscles of the floor of the human oral cavity during intrauterine development]. By means of histological, neurohistological, histochemical and morphometrical techniques the development, number and histotopography of neuromuscular spindles have been studied in 860 muscles of the mouth cavity fundus obtained from 108 human embryos, fetuses and newborns. In genioglossal and in geniohyoid muscles, the spindles are layed down at the 7th week of gestation. Their differentiation starts at the 9th week -- with forming the first sensitive endings, nuclear bursa and cellular elements of the spindle capsule. By the 14th week, the subcapsular space becomes evident, and by the 20th week of embryogenesis neuromuscular spindles resemble definitive structures. In the anterior belly of the digastric muscle, the foundation and initial differentiation of the spindles is retarded. The mylohyoid muscle has no spindles. Morphogenesis of neuromuscular spindles has been studied with special reference to the beginning of functional activity of the fundal muscles in the mouth cavity during embryogenesis in view of the theory of systemogenesis."} {"id": "PMID:156016", "title": "[Comparative characteristics of villous chorionic polysaccharides during the first 3 months of human uterine and tubal pregnancy].", "content": "Qualitative composition of polysaccharides has been studied in 100 chorions of human fetuses, 3.5--12 weeks of embryonic development, 40 of them have been obtained from tubal pregnansies. It has been stated that in villous stroma of the tubal pregnancy at the 4--5th week of gestation, sulphate polysaccharides appear that demonstrates an earlier maturation of villi at this type of pregnancy. It is possible that in the formation of intracellular substance of the villous stroma together with fibroblasts Kastschenko -- Hoffbauer's cells also participate. A characteristic feature for the tubal pregnancy is the appearance of distrophically changed villi beginning from the 4th week of gestation. In plasmodiotrophoblast of such villi the amount of Hale-positive and PAS-positive substances is sharply decreasing, and neutral polysaccharides, chondroitin-4-sulfate, chondroitin-6-sulfate and dermatan-sulfate (small amount) are intensively accumulating in the stroma.", "contents": "[Comparative characteristics of villous chorionic polysaccharides during the first 3 months of human uterine and tubal pregnancy]. Qualitative composition of polysaccharides has been studied in 100 chorions of human fetuses, 3.5--12 weeks of embryonic development, 40 of them have been obtained from tubal pregnansies. It has been stated that in villous stroma of the tubal pregnancy at the 4--5th week of gestation, sulphate polysaccharides appear that demonstrates an earlier maturation of villi at this type of pregnancy. It is possible that in the formation of intracellular substance of the villous stroma together with fibroblasts Kastschenko -- Hoffbauer's cells also participate. A characteristic feature for the tubal pregnancy is the appearance of distrophically changed villi beginning from the 4th week of gestation. In plasmodiotrophoblast of such villi the amount of Hale-positive and PAS-positive substances is sharply decreasing, and neutral polysaccharides, chondroitin-4-sulfate, chondroitin-6-sulfate and dermatan-sulfate (small amount) are intensively accumulating in the stroma."} {"id": "PMID:156017", "title": "Studies of antithyroid antibodies in Down's syndrome.", "content": "The presence of antithyroid antibodies (antithyroglobulin and antimicrosomal) in serum of patients with Down's syndrome and their respective mothers were studied based on data from the literature, showing a possible correlation between the presence of these antibodies in the serum of mothers and the birth of mongoloid children. Antithyroid antibodies were studied in 40 patients with Down's syndrome, with ages ranging from 5 months to 21 years old, 24 males and 16 females and in the respective mothers whose ages varied from 22 to 66 years. In none of the analyzed sera of the mongoloids as well of their mothers, the authors were able to detect the antithyroid antibodies studied.", "contents": "Studies of antithyroid antibodies in Down's syndrome. The presence of antithyroid antibodies (antithyroglobulin and antimicrosomal) in serum of patients with Down's syndrome and their respective mothers were studied based on data from the literature, showing a possible correlation between the presence of these antibodies in the serum of mothers and the birth of mongoloid children. Antithyroid antibodies were studied in 40 patients with Down's syndrome, with ages ranging from 5 months to 21 years old, 24 males and 16 females and in the respective mothers whose ages varied from 22 to 66 years. In none of the analyzed sera of the mongoloids as well of their mothers, the authors were able to detect the antithyroid antibodies studied."} {"id": "PMID:156020", "title": "Modifications of the local immune response to Vibrio cholerate attributed to the intestinal microbial flora of the mouse.", "content": "Oral immunisation studies in germfree, specific pathogen-free (SPF) and conventionalised mice illustrated that the autochthonous gut flora can have a suppressive effect on the induction of a local intestinal immune response to Vibrio cholerae. Temporary colonisation of the small bowel by viable vibrios occurred only in the germfree animal. The lack of colonisation in SPF and conventionalised mice was presumably a cause of their lower coproantibody responses. Prevention of colonisation was probably due to bacterial antagonism rather than to cross-reaction antibodies. This conclusion was reinforced by studies involving oral immunisation of SPF mice maintained on streptomycin, and of conventionalised ex germfree mice. In addition to the increased protective coporantibody response of animals with reduced gut flora, there were increased levels of non-complement-fixing protective antibodies in their serum, which were probably derived from the guy lamina propria.", "contents": "Modifications of the local immune response to Vibrio cholerate attributed to the intestinal microbial flora of the mouse. Oral immunisation studies in germfree, specific pathogen-free (SPF) and conventionalised mice illustrated that the autochthonous gut flora can have a suppressive effect on the induction of a local intestinal immune response to Vibrio cholerae. Temporary colonisation of the small bowel by viable vibrios occurred only in the germfree animal. The lack of colonisation in SPF and conventionalised mice was presumably a cause of their lower coproantibody responses. Prevention of colonisation was probably due to bacterial antagonism rather than to cross-reaction antibodies. This conclusion was reinforced by studies involving oral immunisation of SPF mice maintained on streptomycin, and of conventionalised ex germfree mice. In addition to the increased protective coporantibody response of animals with reduced gut flora, there were increased levels of non-complement-fixing protective antibodies in their serum, which were probably derived from the guy lamina propria."} {"id": "PMID:156021", "title": "Purification and properties of the adenosine triphosphatase released from the liver mitochondrial membrane by chloroform.", "content": "1. Soluble ATPase (adenosine triphosphatase) activity is released when rat liver submitochondrial particles are shaken with chloroform, provided that ATP or glycerol is present in the suspending medium. The extraction is very rapid and appears to be complete. 2. The ATPase of the chloroform extract is about 50% pure and can be readily purified to a specific activity of 60-70mumol/min per mg of protein by (NH(4))(2)SO(4) fractionation and column chromatography on Sephadex G-200. 3. The particulate and soluble ATPases have many similar properties, including their K(m) values for ATP, activation by various metal ions, hydrolytic activity with other nucleotides and stimulation by bicarbonate ions. 4. Unlike the particulate enzyme, the soluble enzyme is cold-labile and insensitive to oligomycin. 5. The molecular weight indicated by the mobility of the soluble ATPase on Sepharose 6B is 360000. 6. The soluble ATPase combines very readily with liver submitochondrial particles depleted of ATPase by salt extraction, and oligomycin-sensitivity is restored. Very little recombination of the enzyme occurs with chloroform-extracted particles. 7. The soluble enzyme contains orcinol-reactive material, suggesting that it may be a glycoprotein. The carbohydrate content was estimated to be 1-2% by weight. 8. It is concluded that the liver ATPase obtained by the chloroform extraction method of Beechey, Hubbard, Linnett, Mitchell & Munn [(1975) Biochem. J.148, 533-537] is similar to other preparations described previously and that this method is superior in simplicity and speed.", "contents": "Purification and properties of the adenosine triphosphatase released from the liver mitochondrial membrane by chloroform. 1. Soluble ATPase (adenosine triphosphatase) activity is released when rat liver submitochondrial particles are shaken with chloroform, provided that ATP or glycerol is present in the suspending medium. The extraction is very rapid and appears to be complete. 2. The ATPase of the chloroform extract is about 50% pure and can be readily purified to a specific activity of 60-70mumol/min per mg of protein by (NH(4))(2)SO(4) fractionation and column chromatography on Sephadex G-200. 3. The particulate and soluble ATPases have many similar properties, including their K(m) values for ATP, activation by various metal ions, hydrolytic activity with other nucleotides and stimulation by bicarbonate ions. 4. Unlike the particulate enzyme, the soluble enzyme is cold-labile and insensitive to oligomycin. 5. The molecular weight indicated by the mobility of the soluble ATPase on Sepharose 6B is 360000. 6. The soluble ATPase combines very readily with liver submitochondrial particles depleted of ATPase by salt extraction, and oligomycin-sensitivity is restored. Very little recombination of the enzyme occurs with chloroform-extracted particles. 7. The soluble enzyme contains orcinol-reactive material, suggesting that it may be a glycoprotein. The carbohydrate content was estimated to be 1-2% by weight. 8. It is concluded that the liver ATPase obtained by the chloroform extraction method of Beechey, Hubbard, Linnett, Mitchell & Munn [(1975) Biochem. J.148, 533-537] is similar to other preparations described previously and that this method is superior in simplicity and speed."} {"id": "PMID:156022", "title": "Mixed anhydrides of nucleotides and mesitylenecarboxylic acid as new specific inhibitors of mitochondrial adenosien triphosphatase.", "content": "Mixed anhydrides of nucleoside triphosphates and mesitylenecarboxylic acid inhibit soluble mitochondrial ATPase (adenosine triphosphatase), but do not inhibit ATPase of submitochondrial particles. Inhibition of soluble mitochondrial ATPase by the mixed anhydride of epsilon-ATP and mesitylenecarboxylic acid is followed by the covalent binding of one nucleotide residue to a molecule of the protein. It is suggested that this covalent binding occurs in the catalytic site of the mitochondrial ATPase. The mixed anhydride of ADP and mesitylenecarboxylic acid inhibits the ATPase activity of submitochondrial particles and has no effect on the activity of soluble mitochondrial ATPase. After separation of the submitochondrial particles from the mixed anhydride of ADP and mesitylenecarboxylic acid, their ATPase activity is restored to its original value (half-time of reactivation 3--4 min). Incubation of submitochondrial particles or soluble mitochondrial ATPase with the mixed anhydride of ADP and mesitylenecarboxylic acid results in AMP formation.", "contents": "Mixed anhydrides of nucleotides and mesitylenecarboxylic acid as new specific inhibitors of mitochondrial adenosien triphosphatase. Mixed anhydrides of nucleoside triphosphates and mesitylenecarboxylic acid inhibit soluble mitochondrial ATPase (adenosine triphosphatase), but do not inhibit ATPase of submitochondrial particles. Inhibition of soluble mitochondrial ATPase by the mixed anhydride of epsilon-ATP and mesitylenecarboxylic acid is followed by the covalent binding of one nucleotide residue to a molecule of the protein. It is suggested that this covalent binding occurs in the catalytic site of the mitochondrial ATPase. The mixed anhydride of ADP and mesitylenecarboxylic acid inhibits the ATPase activity of submitochondrial particles and has no effect on the activity of soluble mitochondrial ATPase. After separation of the submitochondrial particles from the mixed anhydride of ADP and mesitylenecarboxylic acid, their ATPase activity is restored to its original value (half-time of reactivation 3--4 min). Incubation of submitochondrial particles or soluble mitochondrial ATPase with the mixed anhydride of ADP and mesitylenecarboxylic acid results in AMP formation."} {"id": "PMID:156026", "title": "Long term chrysotherapy: incidence of toxicity and efficacy during sequential time periods.", "content": "The frequency and incidence of certain forms of toxicity in patients receiving long term chrysotherapy for rheumatoid arthritis have been reliably calculated for defined, sequential time periods. Ninety-four patients who received 100 courses of gold therapy for a total treatment period of 134.4 patient-years were followed at one gold therapy clinic. For the period of 0--3 months, the incidences of rash, mouth ulcer, and proteinuria were 9.8, 4.0, and 1.8 episodes per 10,000 patients/month, respectively. However, the incidence of these forms of toxicity decreased progressively in subsequent time periods of continued chrysotherapy. No similar decrease was noted in the incidence of thrombocytopenia, but it would appear that the methodology used in monitoring significantly affects the incidence of clinically important thrombocytopenia. No predictive correlates could be determined for patients who had gone into sustained remission. However, the data strongly suggest that patients who improve within 6 months may continue chrysotherapy for at least up to 3 years with an increasing margin of safety for mucocutaneous and renal toxicity.", "contents": "Long term chrysotherapy: incidence of toxicity and efficacy during sequential time periods. The frequency and incidence of certain forms of toxicity in patients receiving long term chrysotherapy for rheumatoid arthritis have been reliably calculated for defined, sequential time periods. Ninety-four patients who received 100 courses of gold therapy for a total treatment period of 134.4 patient-years were followed at one gold therapy clinic. For the period of 0--3 months, the incidences of rash, mouth ulcer, and proteinuria were 9.8, 4.0, and 1.8 episodes per 10,000 patients/month, respectively. However, the incidence of these forms of toxicity decreased progressively in subsequent time periods of continued chrysotherapy. No similar decrease was noted in the incidence of thrombocytopenia, but it would appear that the methodology used in monitoring significantly affects the incidence of clinically important thrombocytopenia. No predictive correlates could be determined for patients who had gone into sustained remission. However, the data strongly suggest that patients who improve within 6 months may continue chrysotherapy for at least up to 3 years with an increasing margin of safety for mucocutaneous and renal toxicity."} {"id": "PMID:156029", "title": "[Pharmacokinetics of fominoben-HCl in the dog and the rabbit (author's transl)].", "content": "The pharmacokinetics of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)-methyl]-aminomethyl)benzanilide-hydrochloride (P-B 89 Cl, fominoben-HCl, Noleptan) was studied in dog and rabbit following a dose of 3 mg/kg on i.v. and p.o. administration of the 44C-labelled compound. Absorption: The compound is absorbed fast in the dog and very fast in the rabbit. Practically the entire dose is absorbed by the two species. Maximum levels in blood: dog 0.5 microgram/ml, rabbit 0.8 microgram/ml, in the plasma: dog 0.6 microgram/ml, rabbit 1.2 microgram/ml at 1--2 h p.a. and 15--30 min p.a. Elimination: The elimination from blood and plasma proceeds biphasically. 1st half-life: 1--2 h, 2nd half-life: 19--27 h (higher values for the rabbit). The dog eliminates preponderantly via the bile with the faeces, the rabbit via the kidneys: Dog: 19% in urine and 63% in faeces, rabbit 79% in urine and 16% in faeces, measured up to 96 h p.a. One rabbit excreted 70% via the urine up to 7 h p.a. The half-lives of urinary elimination are very well comparable with the figures for plasma. Biotransformation: Plasma (maximum level): Dog: Visible amounts of parent compound (M0), Rabbit: Traces M0, much M2. Urine (0--24 h p.a.): Dog: Traces: M0, Rabbit: Traces M0, much M2.", "contents": "[Pharmacokinetics of fominoben-HCl in the dog and the rabbit (author's transl)]. The pharmacokinetics of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)-methyl]-aminomethyl)benzanilide-hydrochloride (P-B 89 Cl, fominoben-HCl, Noleptan) was studied in dog and rabbit following a dose of 3 mg/kg on i.v. and p.o. administration of the 44C-labelled compound. Absorption: The compound is absorbed fast in the dog and very fast in the rabbit. Practically the entire dose is absorbed by the two species. Maximum levels in blood: dog 0.5 microgram/ml, rabbit 0.8 microgram/ml, in the plasma: dog 0.6 microgram/ml, rabbit 1.2 microgram/ml at 1--2 h p.a. and 15--30 min p.a. Elimination: The elimination from blood and plasma proceeds biphasically. 1st half-life: 1--2 h, 2nd half-life: 19--27 h (higher values for the rabbit). The dog eliminates preponderantly via the bile with the faeces, the rabbit via the kidneys: Dog: 19% in urine and 63% in faeces, rabbit 79% in urine and 16% in faeces, measured up to 96 h p.a. One rabbit excreted 70% via the urine up to 7 h p.a. The half-lives of urinary elimination are very well comparable with the figures for plasma. Biotransformation: Plasma (maximum level): Dog: Visible amounts of parent compound (M0), Rabbit: Traces M0, much M2. Urine (0--24 h p.a.): Dog: Traces: M0, Rabbit: Traces M0, much M2."} {"id": "PMID:156031", "title": "[Measurement of global diffusion capacity for CO, membrane diffusion capacity for CO and capillary blood volume in patients with bronchial emphysema after fominoben HCl. Short- and long-time trials (author's transl)].", "content": "The effect of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)-benzanilide hydrochloride (fominoben HCl, P-B 89 Cl, Noleptan) on the global and membrane diffusion capacities and on the capillary blood volume in patients with emphysematous bronchitis is described. All 3 parameters, independent of the severity of the emphysema and the resulting respiratory insufficiency, are increased. It can thus be concluded that fominoben by improving the ventilation-perfusion ratio leads to an enlargement of the active diffusion surface (capillary surface), from which the increase in the global diffusion capacity results. The site of action of fominoben for its positive effect on respiration is thus established as being in the alveoli.", "contents": "[Measurement of global diffusion capacity for CO, membrane diffusion capacity for CO and capillary blood volume in patients with bronchial emphysema after fominoben HCl. Short- and long-time trials (author's transl)]. The effect of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)-benzanilide hydrochloride (fominoben HCl, P-B 89 Cl, Noleptan) on the global and membrane diffusion capacities and on the capillary blood volume in patients with emphysematous bronchitis is described. All 3 parameters, independent of the severity of the emphysema and the resulting respiratory insufficiency, are increased. It can thus be concluded that fominoben by improving the ventilation-perfusion ratio leads to an enlargement of the active diffusion surface (capillary surface), from which the increase in the global diffusion capacity results. The site of action of fominoben for its positive effect on respiration is thus established as being in the alveoli."} {"id": "PMID:156038", "title": "Plasminogen activation transforms the morphology of quiescent 3T3 cell monolayers and initiates growth.", "content": "Plasminogen activator of cell origin converts the plasma protein plasminogen to the proteolytic enzyme plasmin. Recently, high levels of activator have been observed to be particularly associated with tumours and transformed cells, and a functional relationship between plasminogen activation and malignancy has been proposed. In this paper we have attempted to induce transformation-like morphology and growth in a population of confluent quiescent cells in tissue culture, by inducing plasminogen activation. Untransformed 3T3 cells grown to confluence in plasminogen-free medium were subjected to plasminogen activation by the addition of urokinase and plasminogen or plasminogen-containing acid-treated serum, or plasmin. Under these conditions, the previously well ordered monolayers became disrupted, with multilayering, and discontinuities in the cell sheet, and the cells simultaneously grew to significantly higher densities. Removal of the plasmin-containing medium supplements effected some restoration of normal morphology. Thus, lhen plasmin was present 3T3 cells did not become transformed, but expresses transformation-like features. Well ordered monolayer morphology and quiescence in 3T3 cells at confluence are therefore dependent upon the absence of plasminogen activation.", "contents": "Plasminogen activation transforms the morphology of quiescent 3T3 cell monolayers and initiates growth. Plasminogen activator of cell origin converts the plasma protein plasminogen to the proteolytic enzyme plasmin. Recently, high levels of activator have been observed to be particularly associated with tumours and transformed cells, and a functional relationship between plasminogen activation and malignancy has been proposed. In this paper we have attempted to induce transformation-like morphology and growth in a population of confluent quiescent cells in tissue culture, by inducing plasminogen activation. Untransformed 3T3 cells grown to confluence in plasminogen-free medium were subjected to plasminogen activation by the addition of urokinase and plasminogen or plasminogen-containing acid-treated serum, or plasmin. Under these conditions, the previously well ordered monolayers became disrupted, with multilayering, and discontinuities in the cell sheet, and the cells simultaneously grew to significantly higher densities. Removal of the plasmin-containing medium supplements effected some restoration of normal morphology. Thus, lhen plasmin was present 3T3 cells did not become transformed, but expresses transformation-like features. Well ordered monolayer morphology and quiescence in 3T3 cells at confluence are therefore dependent upon the absence of plasminogen activation."} {"id": "PMID:156042", "title": "Isolation of plasma membrane vesicles, derived from transverse tubules, by selective homogenization of subcellular fractions of frog skeletal muscle in isotonic media.", "content": "A new technique for isolating fragmented plasma membranes from skeletal muscle has been developed that is based on gentle mechanical disruption of selected homogenate fractions. (Na+ + K+)-stimulated, Mg2+-dependent ATPase was used as an enzymatic marker for the plasma membrane, Ca2+-stimulated, Mg2+-dependent ATPase as a marker for sarcoplasmic reticulum, and succinate dehydrogenase for mitochondria. Cell segments in an amber low-speed (800 x g) pellet of a frog muscle homogenate were disrupted by repeated gentle shearing with a Polytron homogenizer. Sarcoplasmic reticulum was released into the low-speed supernatant, whereas most of the plasma membrane marker remained in a white, fluffy layer of the sediment, which contained sarcolemma and myofibrils. Additional gentle shearing of the white low-speed sediment extracted plasma membranes in a form that required centrifugation at 100,000 x g for pelleting. This pellet, the fragmented plasma membrane fraction, had a relatively high specific activity of (Na+ + K+)-stimulated ATPase compared with the other fractions, but it had essentially no Ca2+-stimulated ATPase activity and only a small percentage of the succinate dehydrogenase activity of the homogenate. Experimental evidence suggests that the fragmented plasma membrane fraction is derived from delicate transverse tubules rather than from the thicker, basement membrane-coated sarcolemmal sheath of muscle cells. Electron microscopy showed small vesicles lined bu a single thin membrane. Hydroxyproline, a characteristic constituent of collagen and basememt membrane, could not be detected in this fraction.", "contents": "Isolation of plasma membrane vesicles, derived from transverse tubules, by selective homogenization of subcellular fractions of frog skeletal muscle in isotonic media. A new technique for isolating fragmented plasma membranes from skeletal muscle has been developed that is based on gentle mechanical disruption of selected homogenate fractions. (Na+ + K+)-stimulated, Mg2+-dependent ATPase was used as an enzymatic marker for the plasma membrane, Ca2+-stimulated, Mg2+-dependent ATPase as a marker for sarcoplasmic reticulum, and succinate dehydrogenase for mitochondria. Cell segments in an amber low-speed (800 x g) pellet of a frog muscle homogenate were disrupted by repeated gentle shearing with a Polytron homogenizer. Sarcoplasmic reticulum was released into the low-speed supernatant, whereas most of the plasma membrane marker remained in a white, fluffy layer of the sediment, which contained sarcolemma and myofibrils. Additional gentle shearing of the white low-speed sediment extracted plasma membranes in a form that required centrifugation at 100,000 x g for pelleting. This pellet, the fragmented plasma membrane fraction, had a relatively high specific activity of (Na+ + K+)-stimulated ATPase compared with the other fractions, but it had essentially no Ca2+-stimulated ATPase activity and only a small percentage of the succinate dehydrogenase activity of the homogenate. Experimental evidence suggests that the fragmented plasma membrane fraction is derived from delicate transverse tubules rather than from the thicker, basement membrane-coated sarcolemmal sheath of muscle cells. Electron microscopy showed small vesicles lined bu a single thin membrane. Hydroxyproline, a characteristic constituent of collagen and basememt membrane, could not be detected in this fraction."} {"id": "PMID:156044", "title": "(Ca2+ + Mg2+)-ATPase activator: its presence in human red blood cells and rabbit skeletal muscle.", "content": "We find that both human red blood cells and rabbit skeletal muscle contain a soluble activator which can stimulate (Ca2+ + Mg2+)-ATPase activity. The activator protein from either source can enhance the (Ca2+ + Mg2+)-ATPase of both the red blood cell membrane and the microsomal fraction from skeletal muscle. The data suggest that they are members of the class of Ca2+-binding modulator proteins. A possible physiological role for the skeletal muscle activator protein in the contractile process is discussed.", "contents": "(Ca2+ + Mg2+)-ATPase activator: its presence in human red blood cells and rabbit skeletal muscle. We find that both human red blood cells and rabbit skeletal muscle contain a soluble activator which can stimulate (Ca2+ + Mg2+)-ATPase activity. The activator protein from either source can enhance the (Ca2+ + Mg2+)-ATPase of both the red blood cell membrane and the microsomal fraction from skeletal muscle. The data suggest that they are members of the class of Ca2+-binding modulator proteins. A possible physiological role for the skeletal muscle activator protein in the contractile process is discussed."} {"id": "PMID:156045", "title": "Purification and partial characterization of different forms of phosphofructokinase in man.", "content": "Phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) from human muscle, brain, heart and granulocytes has been purified using a two or three step purification procedure. The main step is Blue Dextran-Sepharose 4B chromatography with selective elution of phosphofructokinase by formation of the ternary complex ADP or ATP-fructose-6-P-enzyme. Muscle and heart contain only enzyme subunits with a molecular weight of 85,000. This type of subunit is predominnant in brain, where it co-exists with subunits of about 80,000 daltons. A single type of subunits is found in the granulocytes, with a molecular weight of 80,000. Anti-muscle phosphofructokinase antiserum reacts only with M-type enzyme. Anti-granulocyte enzyme antiserum, absorbed by pure brain phosphofructokinase, exhibits a narrow specificity against the so-called L-type enzyme. Anti-brain antiserum, absorbed by pure muscle phosphofructokinase and partly purified red cell enzyme, exhibits a narrow specificity against a phosphofructokinase form predominant in fibroblasts and present in brain (F-type).", "contents": "Purification and partial characterization of different forms of phosphofructokinase in man. Phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) from human muscle, brain, heart and granulocytes has been purified using a two or three step purification procedure. The main step is Blue Dextran-Sepharose 4B chromatography with selective elution of phosphofructokinase by formation of the ternary complex ADP or ATP-fructose-6-P-enzyme. Muscle and heart contain only enzyme subunits with a molecular weight of 85,000. This type of subunit is predominnant in brain, where it co-exists with subunits of about 80,000 daltons. A single type of subunits is found in the granulocytes, with a molecular weight of 80,000. Anti-muscle phosphofructokinase antiserum reacts only with M-type enzyme. Anti-granulocyte enzyme antiserum, absorbed by pure brain phosphofructokinase, exhibits a narrow specificity against the so-called L-type enzyme. Anti-brain antiserum, absorbed by pure muscle phosphofructokinase and partly purified red cell enzyme, exhibits a narrow specificity against a phosphofructokinase form predominant in fibroblasts and present in brain (F-type)."} {"id": "PMID:156046", "title": "Vocalization and looking behaviour of Down's syndrome infants.", "content": "The effect of contingent and non-contingent vocal stimulation on vocalization and looking behaviour was investigated for 10 Down's syndrome infants. There were two experimental sessions consisting of four stages, namely 1 min base-line, 1 min experimental condition, a further 1 min base-line and a final 2 min experimental condition. Maternal vocal stimulation was contingent upon infant vocalization for the experimental conditions of one session and was presented every 10 s independent of infant vocalization for the experimental conditions of the other session. Neither condition increased infant vocalization but there was a significant decrease in looking at mother during the base-line stages which followed maternal vocalization (F = 5.07, d.f. = 4, 28, P less than 0.01). It is suggested that looking behaviour may be an important indication of competence in pre-linguistic social communication for developmentally delayed infants.", "contents": "Vocalization and looking behaviour of Down's syndrome infants. The effect of contingent and non-contingent vocal stimulation on vocalization and looking behaviour was investigated for 10 Down's syndrome infants. There were two experimental sessions consisting of four stages, namely 1 min base-line, 1 min experimental condition, a further 1 min base-line and a final 2 min experimental condition. Maternal vocal stimulation was contingent upon infant vocalization for the experimental conditions of one session and was presented every 10 s independent of infant vocalization for the experimental conditions of the other session. Neither condition increased infant vocalization but there was a significant decrease in looking at mother during the base-line stages which followed maternal vocalization (F = 5.07, d.f. = 4, 28, P less than 0.01). It is suggested that looking behaviour may be an important indication of competence in pre-linguistic social communication for developmentally delayed infants."} {"id": "PMID:156047", "title": "A radiological approach to infertility--hysterosalpingography.", "content": "The hysterosalpingograms of 98 patients with infertility were reviewed with reference to technical problems, radiological features of each pathology and accuracy of reporting. Findings were confirmed by review of the reports of laparotomy or laparoscopy on all patients. Of the total number of fallopian tubes investigated (196), 70 hydrosalpinges were correctly diagnosed from a total of 77. Agreement between HSG and operation was achieved in 123 of 127 fallopian tubes with peritubal adhesions, in all six of those with cornual spasm and in eight with cornual occlusion. In 16 of 20 fallopian tubes with partial distal occlusion, reporting was correct. With the potential accuracy of HSG diagnosis, we contend that it should be a preliminary procedure in every case, and in many may be the only investigation of tubal patency required prior to surgery or conservative management.", "contents": "A radiological approach to infertility--hysterosalpingography. The hysterosalpingograms of 98 patients with infertility were reviewed with reference to technical problems, radiological features of each pathology and accuracy of reporting. Findings were confirmed by review of the reports of laparotomy or laparoscopy on all patients. Of the total number of fallopian tubes investigated (196), 70 hydrosalpinges were correctly diagnosed from a total of 77. Agreement between HSG and operation was achieved in 123 of 127 fallopian tubes with peritubal adhesions, in all six of those with cornual spasm and in eight with cornual occlusion. In 16 of 20 fallopian tubes with partial distal occlusion, reporting was correct. With the potential accuracy of HSG diagnosis, we contend that it should be a preliminary procedure in every case, and in many may be the only investigation of tubal patency required prior to surgery or conservative management."} {"id": "PMID:156048", "title": "Fissuring of the posterior annulus fibrosus in the lumbar spine.", "content": "Severe back-ache in young adults may present a difficult clinical problem when the absence of neurological signs results in delayed diagnosis. Fourteen patients, with discographic evidence of posterior annular fissuring are reported. The discrepancy between painful disability and negative radiographic examination including radiculography is stressed. Discography has proved to be the investigation of choice in these patients. This will demonstrate the morphology of the lesion and reproduce the symptomatology in the majority of cases. The clinical implications are discussed.", "contents": "Fissuring of the posterior annulus fibrosus in the lumbar spine. Severe back-ache in young adults may present a difficult clinical problem when the absence of neurological signs results in delayed diagnosis. Fourteen patients, with discographic evidence of posterior annular fissuring are reported. The discrepancy between painful disability and negative radiographic examination including radiculography is stressed. Discography has proved to be the investigation of choice in these patients. This will demonstrate the morphology of the lesion and reproduce the symptomatology in the majority of cases. The clinical implications are discussed."} {"id": "PMID:156054", "title": "Prevalence of facial acne vulgaris in late adolescence and in adults.", "content": "A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution.", "contents": "Prevalence of facial acne vulgaris in late adolescence and in adults. A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution."} {"id": "PMID:156059", "title": "Bicarbonate-activated ATPase activity in renal cortex of chronically acidotic rats.", "content": "The effect of chronic NH4Cl-induced acidosis on the activity of a bicarbonate-activated component of ATPase was studied in homogenates of renal tissue from Wistar rats. This particular component of ATPase, which is maximally stimulated by 50 mM bicarbonate, and is insensitive to the action of ouabain, has been implicated in the active transport of bicarbonate in various tissues. The activity of this enzyme in cortical homogenates from an acidotic group of animals was 4.3 +/- 0.4 mumol Pi/mg protein per hour compared with 5.8 +/- 0.3 mumol Pi/mg protein per hour in a control group (p less than 0.02). No significant change in bicarbonate ATPase activity was observed in medullary homogenates, and NaK-ATPase activity remained the same in cortex and medulla of both groups. Subcellular fractionation of the cortical tissue homogenates revealed that bicarbonate ATPase activity in a microsomal fraction from acidotic animals was 6.5 +/- 1.1 mumol Pi/mg protein per hour compared with 9.4 +/- 1.2 mumol Pi/mg protein per hour in control animals (p less than 0.02). Bicarbonate ATPase activity in other subcellular fractions was not different in the two groups of animals. These findings are compatible with the hypothesis that a certain percentage of bicarbonate reabsorption in the nephron is mediated by a bicarbonate-activated component of ATPase.", "contents": "Bicarbonate-activated ATPase activity in renal cortex of chronically acidotic rats. The effect of chronic NH4Cl-induced acidosis on the activity of a bicarbonate-activated component of ATPase was studied in homogenates of renal tissue from Wistar rats. This particular component of ATPase, which is maximally stimulated by 50 mM bicarbonate, and is insensitive to the action of ouabain, has been implicated in the active transport of bicarbonate in various tissues. The activity of this enzyme in cortical homogenates from an acidotic group of animals was 4.3 +/- 0.4 mumol Pi/mg protein per hour compared with 5.8 +/- 0.3 mumol Pi/mg protein per hour in a control group (p less than 0.02). No significant change in bicarbonate ATPase activity was observed in medullary homogenates, and NaK-ATPase activity remained the same in cortex and medulla of both groups. Subcellular fractionation of the cortical tissue homogenates revealed that bicarbonate ATPase activity in a microsomal fraction from acidotic animals was 6.5 +/- 1.1 mumol Pi/mg protein per hour compared with 9.4 +/- 1.2 mumol Pi/mg protein per hour in control animals (p less than 0.02). Bicarbonate ATPase activity in other subcellular fractions was not different in the two groups of animals. These findings are compatible with the hypothesis that a certain percentage of bicarbonate reabsorption in the nephron is mediated by a bicarbonate-activated component of ATPase."} {"id": "PMID:156060", "title": "Action of oxytocin on mammary gland: influence of hypotonicity.", "content": "The enhancement of the response of an isolated strip of lactating mouse mammary gland to oxytocin, resulting from dilution of the Tyrode solution in which oxytocin is administered, is due to the effects of hypotonicity per se and not to changes in concentration of any of the ions in the bathing solution. Inhibition of membrane ATPase also causes an enhancement, which is probably due to activation of a secondary facilitating mechanism, rather than to enhancement of the entire train of oxytocin-induced reactions. A variety of conditions which alter the response to oxytocin have the same effect on the response to acetylcholine. Hypotonicity can therefore increase the sensitivity of this bioassay for oxytocin, but not its selectivity.", "contents": "Action of oxytocin on mammary gland: influence of hypotonicity. The enhancement of the response of an isolated strip of lactating mouse mammary gland to oxytocin, resulting from dilution of the Tyrode solution in which oxytocin is administered, is due to the effects of hypotonicity per se and not to changes in concentration of any of the ions in the bathing solution. Inhibition of membrane ATPase also causes an enhancement, which is probably due to activation of a secondary facilitating mechanism, rather than to enhancement of the entire train of oxytocin-induced reactions. A variety of conditions which alter the response to oxytocin have the same effect on the response to acetylcholine. Hypotonicity can therefore increase the sensitivity of this bioassay for oxytocin, but not its selectivity."} {"id": "PMID:156061", "title": "Treatment of aortoiliac disease by axillofemoral artery bypass.", "content": "Between July 1, 1971 and June 30, 1977, 45 axillofemoral artery bypass procedures were performed on 39 men and 5 women whose average age was 67.7 years. Twenty-four patients received 25 unilateral axillofemoral bypasses; the remaining 20 patients underwent axillobifemoral artery procedures. The indication for surgery in 42 patients was limb salvage; the other 2 had infected aortic prostheses. All patients in the former group had serious associated disorders which would have made a conventional intra-abdominal procedure hazardous. The early mortality was 2.3% and the late mortality 29.6%. Of these 45 grafts 20 became occluded; however, 8 of the occluded grafts were successfully revised and have remained patent. For the 25 unilateral grafts at risk the 5-year cumulative patency rate determined by life-table methods was 50.6% and for the 20 bilateral grafts it was 89.7%. Our experience indicates that axillobifemoral bypass has a significantly (P less than 0.02) higher patency rate than unilateral axillofemoral bypass and is an acceptable alternative to conventional intra-abdominal procedures in elderly and poor-risk patients with aortoiliac disease.", "contents": "Treatment of aortoiliac disease by axillofemoral artery bypass. Between July 1, 1971 and June 30, 1977, 45 axillofemoral artery bypass procedures were performed on 39 men and 5 women whose average age was 67.7 years. Twenty-four patients received 25 unilateral axillofemoral bypasses; the remaining 20 patients underwent axillobifemoral artery procedures. The indication for surgery in 42 patients was limb salvage; the other 2 had infected aortic prostheses. All patients in the former group had serious associated disorders which would have made a conventional intra-abdominal procedure hazardous. The early mortality was 2.3% and the late mortality 29.6%. Of these 45 grafts 20 became occluded; however, 8 of the occluded grafts were successfully revised and have remained patent. For the 25 unilateral grafts at risk the 5-year cumulative patency rate determined by life-table methods was 50.6% and for the 20 bilateral grafts it was 89.7%. Our experience indicates that axillobifemoral bypass has a significantly (P less than 0.02) higher patency rate than unilateral axillofemoral bypass and is an acceptable alternative to conventional intra-abdominal procedures in elderly and poor-risk patients with aortoiliac disease."} {"id": "PMID:156062", "title": "Pyogenic infections of the adult spine.", "content": "A retrospective analysis of 61 patients forms the basis for this paper's comment on three major types of pyogenic spinal disease. The first group consists of 22 patients with vertebral osteomyelitis and intervertebral discitis. The second group comprises 22 patients in whom the diagnosis of pyogenic spinal disease was made only after failure of discectomy. In retrospect they were shown to have atypical degenerative disc disease and were similar to the first group. The third group of 17 patients, while demonstrating some similarities to the second group, represents true postdiscectomy wound infection. An understanding of the clinical presentation and pathophysiology of pyogenic disease of the spine allows it to be distinguished preoperatively from degenerative disc disease which superficially it resembles. Further, true postdiscectomy wound infection can be distinguished from pyogenic spinal disease misdiagnosed preoperatively. The differences in the results of treatment of these three groups warrant such distinctions.", "contents": "Pyogenic infections of the adult spine. A retrospective analysis of 61 patients forms the basis for this paper's comment on three major types of pyogenic spinal disease. The first group consists of 22 patients with vertebral osteomyelitis and intervertebral discitis. The second group comprises 22 patients in whom the diagnosis of pyogenic spinal disease was made only after failure of discectomy. In retrospect they were shown to have atypical degenerative disc disease and were similar to the first group. The third group of 17 patients, while demonstrating some similarities to the second group, represents true postdiscectomy wound infection. An understanding of the clinical presentation and pathophysiology of pyogenic disease of the spine allows it to be distinguished preoperatively from degenerative disc disease which superficially it resembles. Further, true postdiscectomy wound infection can be distinguished from pyogenic spinal disease misdiagnosed preoperatively. The differences in the results of treatment of these three groups warrant such distinctions."} {"id": "PMID:156063", "title": "Extragenital adenomatoid tumor: Evidence for the mesothelial theory of origin.", "content": "The histogenesis of so-called adenomatoid tumors has been contested. Doubts as to a mesothelial derivation often have been based on the belief that adenomatoid tumors originate exclusively in or nearby genital tract organs. This report documents a histologically typical adenomatoid tumor which developed in the mesentery of the small intestine. Extensive clinical investigations and an uneventful 3-year postoperative follow-up interval confirmed that the tumor was not a metastatic adenocarcinoma or malignant mesothelioma. The extragenital site of origin of this neoplasm provides additional corroborative evidence for the mesothelial origin of adenomatoid tumors. Regardless of their anatomic location, these distinctive neoplasms should be classified as benign adenomatoid mesotheliomas.", "contents": "Extragenital adenomatoid tumor: Evidence for the mesothelial theory of origin. The histogenesis of so-called adenomatoid tumors has been contested. Doubts as to a mesothelial derivation often have been based on the belief that adenomatoid tumors originate exclusively in or nearby genital tract organs. This report documents a histologically typical adenomatoid tumor which developed in the mesentery of the small intestine. Extensive clinical investigations and an uneventful 3-year postoperative follow-up interval confirmed that the tumor was not a metastatic adenocarcinoma or malignant mesothelioma. The extragenital site of origin of this neoplasm provides additional corroborative evidence for the mesothelial origin of adenomatoid tumors. Regardless of their anatomic location, these distinctive neoplasms should be classified as benign adenomatoid mesotheliomas."} {"id": "PMID:156064", "title": "Stimulation of human chorionic gonadotropin by JAr line choriocarcinoma after inhibition of DNA synthesis.", "content": "Treatment of choriocarcinoma cells (JAr line) for 24 hr with methotrexate, fluorodeoxyuridine, 1-beta-D-arabinofuranosylcytosine, or hydroxyurea, in doses that inhibit DNA synthesis, results in a 2.5- to 12-fold increase in human chorionic gonadotropin (HCG) synthesis. Under the conditions of use, these agents do not significantly depress RNA or protein synthesis. Simultaneous addition of thymidine with methotrexate or fluorodeoxyuridine and of deoxycytidine with 1-beta-D-arabinofuranosylcytosine blocks the HCG stimulation. Despite a rapid inhibition of DNA synthesis, HCG stimulation is gradual and reaches a peak after drug removal. Decline in HCG synthesis is coincident with recovery of DNA synthesis, and there is a positive correlation between the duration of inhibition of DNA synthesis and the amount of HCG increase. Although most of the methotrexate-induced stimulation of HCG synthesis occurs after methotrexate removal, preventing protein synthesis during the exposure to methotrexate abrogates the increase. The stimulation of HCG synthesis by methotrexate is more sensitive to protein synthesis inhibition during the first 12 hr of a 24-hr exposure than it is during the second 12 hr. Thus, in accord with the kinetics, specificity, dose dependence, and protein synthesis requirement, HCG synthesis seems to be stimulated as a direct consequence of inhibition of DNA synthesis, with a requirement for some other protein synthesis-dependent event(s) preceding the stimulation.", "contents": "Stimulation of human chorionic gonadotropin by JAr line choriocarcinoma after inhibition of DNA synthesis. Treatment of choriocarcinoma cells (JAr line) for 24 hr with methotrexate, fluorodeoxyuridine, 1-beta-D-arabinofuranosylcytosine, or hydroxyurea, in doses that inhibit DNA synthesis, results in a 2.5- to 12-fold increase in human chorionic gonadotropin (HCG) synthesis. Under the conditions of use, these agents do not significantly depress RNA or protein synthesis. Simultaneous addition of thymidine with methotrexate or fluorodeoxyuridine and of deoxycytidine with 1-beta-D-arabinofuranosylcytosine blocks the HCG stimulation. Despite a rapid inhibition of DNA synthesis, HCG stimulation is gradual and reaches a peak after drug removal. Decline in HCG synthesis is coincident with recovery of DNA synthesis, and there is a positive correlation between the duration of inhibition of DNA synthesis and the amount of HCG increase. Although most of the methotrexate-induced stimulation of HCG synthesis occurs after methotrexate removal, preventing protein synthesis during the exposure to methotrexate abrogates the increase. The stimulation of HCG synthesis by methotrexate is more sensitive to protein synthesis inhibition during the first 12 hr of a 24-hr exposure than it is during the second 12 hr. Thus, in accord with the kinetics, specificity, dose dependence, and protein synthesis requirement, HCG synthesis seems to be stimulated as a direct consequence of inhibition of DNA synthesis, with a requirement for some other protein synthesis-dependent event(s) preceding the stimulation."} {"id": "PMID:156066", "title": "Experimental and clinical studies on the formation of antibodies to neocarzinostatin, a new protein antibiotic.", "content": "The injection of clinical doses of neocarzinostatin (NCS) in guinea pigs did not result in antibody formation as judged by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, fluorescence polarization, and passive cutaneous anaphylaxis reaction. This confirmed previous work on passive hemagglutination and passive cutaneous anaphylaxis reaction in a heterocytotropic system in guinea pigs. Forty-eight serum samples from 28 patients who were previously treated with NCS alone (8--161 mg) for a period of 8-85 days did not show any sign of antibody formation as revealed by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, and fluorescence polarization techniques. In a homocytotropic system, the passive cutaneous anaphylaxis reaction was carried out with sera of sensitized guinea pigs and test guinea pigs which revealed that no IgE and IgA antibody to NCS was present in the sensitized sera. Those patients with bladder cancer who did not respond to NCS therapy or exhibit any side effects even after 21 mg were found to have proteolytic activity in their sera which degraded NCS very rapidly as revealed by the fluorescence polarization technique.", "contents": "Experimental and clinical studies on the formation of antibodies to neocarzinostatin, a new protein antibiotic. The injection of clinical doses of neocarzinostatin (NCS) in guinea pigs did not result in antibody formation as judged by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, fluorescence polarization, and passive cutaneous anaphylaxis reaction. This confirmed previous work on passive hemagglutination and passive cutaneous anaphylaxis reaction in a heterocytotropic system in guinea pigs. Forty-eight serum samples from 28 patients who were previously treated with NCS alone (8--161 mg) for a period of 8-85 days did not show any sign of antibody formation as revealed by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, and fluorescence polarization techniques. In a homocytotropic system, the passive cutaneous anaphylaxis reaction was carried out with sera of sensitized guinea pigs and test guinea pigs which revealed that no IgE and IgA antibody to NCS was present in the sensitized sera. Those patients with bladder cancer who did not respond to NCS therapy or exhibit any side effects even after 21 mg were found to have proteolytic activity in their sera which degraded NCS very rapidly as revealed by the fluorescence polarization technique."} {"id": "PMID:156067", "title": "Phase I study of neocarzinostatin in children with cancer.", "content": "Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.", "contents": "Phase I study of neocarzinostatin in children with cancer. Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted."} {"id": "PMID:156069", "title": "Preliminary evaluation of 15 chemotherapeutic agents applied topically in the treatment of mycosis fungoides.", "content": "This is an interim report of a double-blind multi-institutional study to examine the effect of chemotherapeutic agents applied topically to patients with mycosis fungoides. To date, 41 patch tests have been completed using 15 drugs. Five of the drugs produced some improvement, four were highly irritating, and six had no effect. This patch-testing study is a prelude to more extensive therapy trials.", "contents": "Preliminary evaluation of 15 chemotherapeutic agents applied topically in the treatment of mycosis fungoides. This is an interim report of a double-blind multi-institutional study to examine the effect of chemotherapeutic agents applied topically to patients with mycosis fungoides. To date, 41 patch tests have been completed using 15 drugs. Five of the drugs produced some improvement, four were highly irritating, and six had no effect. This patch-testing study is a prelude to more extensive therapy trials."} {"id": "PMID:156072", "title": "Plasma norepinephrine concentration in the coronary sinus in cardiomyopathies.", "content": "In order to evaluate the cardiac sympathetic nerve tone in cardiomyopathies, plasma norepinephrine concentration in the coronary sinus (NE(CS)) and artery (NE(A)) was measured by THI method in five patients with the hypertrophic type (HCM) and in seven with the congestive type (CCM); six patients with functional murmur served as controls. NE(CS) was 182 +/- 39 ng/liter (SEM) in HCM, 288 +/- 47 in CCM, and 306 +/- 65 in controls. The NE(CS) - NE(A) difference (delta NE) was 9 +/- 22 ng/liter in HCM, -57 +/- 34 in CCM, and 81 +/- 29 in controls. Norepinephrine overflow into the coronary sinus,which was calculated by multiplying coronary sinus plasma flow by delta NE, was 0.54 +/- 0.86 ng/min/100gm, -2.81 +/- 1.47, and 3.73 +/- 1.77, respectively. Norepinephrine overflow and delta NE were significantly lower in CCM than in controls. The results suggest than an excessive sympathetic discharge does not exist in HCM and that cardiac sympathetic activity is reduced in CCM.", "contents": "Plasma norepinephrine concentration in the coronary sinus in cardiomyopathies. In order to evaluate the cardiac sympathetic nerve tone in cardiomyopathies, plasma norepinephrine concentration in the coronary sinus (NE(CS)) and artery (NE(A)) was measured by THI method in five patients with the hypertrophic type (HCM) and in seven with the congestive type (CCM); six patients with functional murmur served as controls. NE(CS) was 182 +/- 39 ng/liter (SEM) in HCM, 288 +/- 47 in CCM, and 306 +/- 65 in controls. The NE(CS) - NE(A) difference (delta NE) was 9 +/- 22 ng/liter in HCM, -57 +/- 34 in CCM, and 81 +/- 29 in controls. Norepinephrine overflow into the coronary sinus,which was calculated by multiplying coronary sinus plasma flow by delta NE, was 0.54 +/- 0.86 ng/min/100gm, -2.81 +/- 1.47, and 3.73 +/- 1.77, respectively. Norepinephrine overflow and delta NE were significantly lower in CCM than in controls. The results suggest than an excessive sympathetic discharge does not exist in HCM and that cardiac sympathetic activity is reduced in CCM."} {"id": "PMID:156073", "title": "Inhibition of pyrimidine incorporation without inhibition of DNA synthesis.", "content": "A putative lymphocytic chalone was tested measuring the incorporation of purine and pyrimidine nucleosides and by cytophotometry. The pyrimidine precursors were inhibited but not the purines. Thymidine and deoxycytidine incorporation even performed simultaneously with cytophotometry can be misleading in the analysis of the inhibition of cell division.", "contents": "Inhibition of pyrimidine incorporation without inhibition of DNA synthesis. A putative lymphocytic chalone was tested measuring the incorporation of purine and pyrimidine nucleosides and by cytophotometry. The pyrimidine precursors were inhibited but not the purines. Thymidine and deoxycytidine incorporation even performed simultaneously with cytophotometry can be misleading in the analysis of the inhibition of cell division."} {"id": "PMID:156088", "title": "Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function.", "content": "This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident.", "contents": "Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function. This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident."} {"id": "PMID:156090", "title": "Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.", "content": "Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qpa (pulmonary blood flow) = 2.02 +/- 0.15 liters/min, Zo = 193 +/- 20 dyne sec cm-5 and PVR = 416 +/- 32 dyne sec cm-5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qpa = 3-4 liters/min (mean = 3.80 +/- 0.09, P less than 0.001 different from control group); the other five dogs (group B) developed Qpa = 4-8 liters/min (mean = 5.87 +/- 0.16, P less than 0.001). In group A, Zo = 143 +/- 8 (P less than 0.05) and PVR = 249 +/- 6 (P less than 0.10). In group B, Zo = 90 +/- 5 (P less than 0.005) and PVR = 126 +/- 14 (P less than 0.01). The total input power (potential and kinetic) was 125% above the controls for group A (P less than 0.001) and 264% for group B (P less than 0.001), but the mean energy components increased significantly more than did the pulsatile components. These data demonstrate a lower impedance to pulsatile flow during chronically elevated total flow which effects a reduction in both the work load of the right ventricle and the transmission of energy to the precapillary bed. Analysis of the alterations in characteristic impedance suggests a distinct proximal pulmonary vascular mechanism of decreased vessel stiffness (decreased elastic moduli) for adaptation to chronically elevated flow loads which is in addition to the two geometric alterations of proximal arterial dilation and distal vascular channel recruitment.", "contents": "Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog. Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qpa (pulmonary blood flow) = 2.02 +/- 0.15 liters/min, Zo = 193 +/- 20 dyne sec cm-5 and PVR = 416 +/- 32 dyne sec cm-5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qpa = 3-4 liters/min (mean = 3.80 +/- 0.09, P less than 0.001 different from control group); the other five dogs (group B) developed Qpa = 4-8 liters/min (mean = 5.87 +/- 0.16, P less than 0.001). In group A, Zo = 143 +/- 8 (P less than 0.05) and PVR = 249 +/- 6 (P less than 0.10). In group B, Zo = 90 +/- 5 (P less than 0.005) and PVR = 126 +/- 14 (P less than 0.01). The total input power (potential and kinetic) was 125% above the controls for group A (P less than 0.001) and 264% for group B (P less than 0.001), but the mean energy components increased significantly more than did the pulsatile components. These data demonstrate a lower impedance to pulsatile flow during chronically elevated total flow which effects a reduction in both the work load of the right ventricle and the transmission of energy to the precapillary bed. Analysis of the alterations in characteristic impedance suggests a distinct proximal pulmonary vascular mechanism of decreased vessel stiffness (decreased elastic moduli) for adaptation to chronically elevated flow loads which is in addition to the two geometric alterations of proximal arterial dilation and distal vascular channel recruitment."} {"id": "PMID:156091", "title": "Left axis deviation: a reassessment.", "content": "This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly.", "contents": "Left axis deviation: a reassessment. This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly."} {"id": "PMID:156092", "title": "Influence of aortic insufficiency on the hemodynamic significance of a coronary artery narrowing.", "content": "The coronary hemodynamic effects of controlled aortic insufficiency (AI) were studied in 10 dogs. Coronary blood flow (CBF), before and during reactive hyperemia (RH) with graded coronary diameter narrowings (CN), aortic (Ao) and left ventricular (LV) pressures (P), and aortic blood flow (AoF) were recorded. Opening an adjustable basket catheter, positioned across the aortic valve, created reversible AI quantitated from phasic AoF. AI was regulated so that mean CBF was similar with or without AI. During AI, heart rate and systolic AoP were unchanged, but diastolic AoP declined 14 mm Hg (mean) and end-diastolic LVP increased 8 mm Hg, both p less than 0.05. With CN greater than or equal to 85%, mean CBF decreased with or without AI. Coronary resistance was similar with or without AI. During AI with no CN, peak RH CBF declined significantly and was similar to peak RH with 70% CN without AI. Furthermore, AI with 60% CN caused additional reduction in peak RH and was similar to peak RH with 80% CN without AI. These data suggest that CBF reserve, exposed during RH, is decreased during AI. With AI, a given CN has coronary hemodynamic properties similar to higher degrees of CN without AI. These results may relate to clinical findings of ischemia in patients with AI and no or moderate CN.", "contents": "Influence of aortic insufficiency on the hemodynamic significance of a coronary artery narrowing. The coronary hemodynamic effects of controlled aortic insufficiency (AI) were studied in 10 dogs. Coronary blood flow (CBF), before and during reactive hyperemia (RH) with graded coronary diameter narrowings (CN), aortic (Ao) and left ventricular (LV) pressures (P), and aortic blood flow (AoF) were recorded. Opening an adjustable basket catheter, positioned across the aortic valve, created reversible AI quantitated from phasic AoF. AI was regulated so that mean CBF was similar with or without AI. During AI, heart rate and systolic AoP were unchanged, but diastolic AoP declined 14 mm Hg (mean) and end-diastolic LVP increased 8 mm Hg, both p less than 0.05. With CN greater than or equal to 85%, mean CBF decreased with or without AI. Coronary resistance was similar with or without AI. During AI with no CN, peak RH CBF declined significantly and was similar to peak RH with 70% CN without AI. Furthermore, AI with 60% CN caused additional reduction in peak RH and was similar to peak RH with 80% CN without AI. These data suggest that CBF reserve, exposed during RH, is decreased during AI. With AI, a given CN has coronary hemodynamic properties similar to higher degrees of CN without AI. These results may relate to clinical findings of ischemia in patients with AI and no or moderate CN."} {"id": "PMID:156093", "title": "A comparison of simultaneous measurements of systolic function in the baboon by electromagnetic flowmeter and high frame rate ECG-gated blood pool scintigraphy.", "content": "Left ventricular (LV) systolic timing and relative volume variations were simultaneously measured by electromagnetic flowmeter (EMF) and high frame rate ECG-gated blood pool scintigraphy in five baboons. No significant differences (p greater than 0.1, paired t test) were observed in the time (from R wave) to peak aortic flow (maximum LV ejection rate), time to cessation of aortic flow (end-systole) or in the duration of aortic flow (LV ejection time). A small (approximately 15 msec) but significant systematic difference (p less than 0.02) was noted in the time to onset of aortic flow. The shape of each scintigraphic time-activity curve during systole was compared to an equivalent curve synthesized from 10 EMF flow profiles obtained in the same baboon. Comparison of these paired curves over systolic ejection yielded an average correlation or r = 0.95 (range 0.90--0.99). The ratio of peak flow to stroke volume determined from these data did not differ significantly (p greater than 0.05). In the baboon, quantitative high temporal resolution ECG-gated scintigraphy appears to reflect closely the detailed timing and relative magnitude variation of LV volume during the entire period of systolic ejection. We conclude that the assumptions underlying the scintigraphic method are valid in the baboon during the ejection interval.", "contents": "A comparison of simultaneous measurements of systolic function in the baboon by electromagnetic flowmeter and high frame rate ECG-gated blood pool scintigraphy. Left ventricular (LV) systolic timing and relative volume variations were simultaneously measured by electromagnetic flowmeter (EMF) and high frame rate ECG-gated blood pool scintigraphy in five baboons. No significant differences (p greater than 0.1, paired t test) were observed in the time (from R wave) to peak aortic flow (maximum LV ejection rate), time to cessation of aortic flow (end-systole) or in the duration of aortic flow (LV ejection time). A small (approximately 15 msec) but significant systematic difference (p less than 0.02) was noted in the time to onset of aortic flow. The shape of each scintigraphic time-activity curve during systole was compared to an equivalent curve synthesized from 10 EMF flow profiles obtained in the same baboon. Comparison of these paired curves over systolic ejection yielded an average correlation or r = 0.95 (range 0.90--0.99). The ratio of peak flow to stroke volume determined from these data did not differ significantly (p greater than 0.05). In the baboon, quantitative high temporal resolution ECG-gated scintigraphy appears to reflect closely the detailed timing and relative magnitude variation of LV volume during the entire period of systolic ejection. We conclude that the assumptions underlying the scintigraphic method are valid in the baboon during the ejection interval."} {"id": "PMID:156094", "title": "Physiologic determinants of the electrocardiographic diagnosis of left ventricular hypertrophy.", "content": "The relative importance of left ventricular (LV) geometry, wall thickness, and mass on the inscription of left ventricular hypertrophy (LVH) on the ECG was examined in 93 patients; 36 had no LVH on the ECG, 10 had borderline voltage for LVH, and 47 had LVH on the ECG. LV cineangiograms in the right anterior oblique projection were analyzed for LV end-diastolic volume, free wall thickness (h), semiminor radius (R), LV mass index (LVMI), and the geometric relations described by h/R, mass/volume, and h . R. Although mean LVMI was greater in patients whose ECG voltage was either borderline or diagnostic of LVH, increased LVMI also occurred without LVH on the ECG. None of the variables (h, R, h/R or mass/volume) reliably indicated when LVH would be inscribed on the ECG. The product of h . R, however, defined three electrocardiographic groups; all patients with LVH on their ECG had h . R greater than 2.6 cm2. Wall thickening sufficient to result in an increased LV mass did not result in LVH on the ECG unless sufficient concurrent chamber dilatation was present. Thus, a critical geometric relationship resulting from the interplay of wall thickness and chamber dilatation is necessary for LVH to appear on the ECG. This finding is consistent with the solid-angle theory of electrocardiography as it relates to ventricular hypertrophy.", "contents": "Physiologic determinants of the electrocardiographic diagnosis of left ventricular hypertrophy. The relative importance of left ventricular (LV) geometry, wall thickness, and mass on the inscription of left ventricular hypertrophy (LVH) on the ECG was examined in 93 patients; 36 had no LVH on the ECG, 10 had borderline voltage for LVH, and 47 had LVH on the ECG. LV cineangiograms in the right anterior oblique projection were analyzed for LV end-diastolic volume, free wall thickness (h), semiminor radius (R), LV mass index (LVMI), and the geometric relations described by h/R, mass/volume, and h . R. Although mean LVMI was greater in patients whose ECG voltage was either borderline or diagnostic of LVH, increased LVMI also occurred without LVH on the ECG. None of the variables (h, R, h/R or mass/volume) reliably indicated when LVH would be inscribed on the ECG. The product of h . R, however, defined three electrocardiographic groups; all patients with LVH on their ECG had h . R greater than 2.6 cm2. Wall thickening sufficient to result in an increased LV mass did not result in LVH on the ECG unless sufficient concurrent chamber dilatation was present. Thus, a critical geometric relationship resulting from the interplay of wall thickness and chamber dilatation is necessary for LVH to appear on the ECG. This finding is consistent with the solid-angle theory of electrocardiography as it relates to ventricular hypertrophy."} {"id": "PMID:156095", "title": "Results of ophthalmosonometry and supraorbital photoplethysmography in evaluating carotid arterial stenoses.", "content": "A total of 263 patients underwent either periorbital ophthalmosonometry (Doppler ultrasound) or a combination of ophthalmosonometry and supraorbital photoplethysmography (SOPPG) to determine the presence or absence of a hemodynamically significant lesion (occlusion or greater than 50% reduction in lumen diameter). There were 522 vessels studied with Doppler ultrasound and 272 vessels with a combination of the two modalities. The tests were correlated with carotid arteriography to determine their accuracy. Overall accuracy of the Doppler ultrasound examination was 95%. A normal Doppler ultrasound examination was obtained in 367 vessels and arteriography confirmed the absence of a hemodynamically significant lesion in 93%. Of 155 vessels with an abnormal Doppler examination, 149 (96%) were proven on arteriography to have hemodynamically significant lesions. The Doppler ultrasound examination had a high incidence of false-negative examinations (26%) in those vessels that were between 50% and 99% stenotic, however. The SOPPG alone had a high incidence of false-positive examinations (19%); however, in 155 vessels with a normal SOPPG, 98% were proved to have no hemodynamically significant lesion. The combination of Doppler ultrasound and SOPPG was highly accurate in identifying patients with hemodynamically significant lesions. Of 97 vessels with such lesions, 96 (99%) had either an abnormal Doppler ultrasound examination or an abnormal SOPPG. In 240 vessels with concordant results of the Doppler ultrasound and SOPPG, the presence or absence of a hemodynamically significant lesion was accurately predicted in 235 (98%).", "contents": "Results of ophthalmosonometry and supraorbital photoplethysmography in evaluating carotid arterial stenoses. A total of 263 patients underwent either periorbital ophthalmosonometry (Doppler ultrasound) or a combination of ophthalmosonometry and supraorbital photoplethysmography (SOPPG) to determine the presence or absence of a hemodynamically significant lesion (occlusion or greater than 50% reduction in lumen diameter). There were 522 vessels studied with Doppler ultrasound and 272 vessels with a combination of the two modalities. The tests were correlated with carotid arteriography to determine their accuracy. Overall accuracy of the Doppler ultrasound examination was 95%. A normal Doppler ultrasound examination was obtained in 367 vessels and arteriography confirmed the absence of a hemodynamically significant lesion in 93%. Of 155 vessels with an abnormal Doppler examination, 149 (96%) were proven on arteriography to have hemodynamically significant lesions. The Doppler ultrasound examination had a high incidence of false-negative examinations (26%) in those vessels that were between 50% and 99% stenotic, however. The SOPPG alone had a high incidence of false-positive examinations (19%); however, in 155 vessels with a normal SOPPG, 98% were proved to have no hemodynamically significant lesion. The combination of Doppler ultrasound and SOPPG was highly accurate in identifying patients with hemodynamically significant lesions. Of 97 vessels with such lesions, 96 (99%) had either an abnormal Doppler ultrasound examination or an abnormal SOPPG. In 240 vessels with concordant results of the Doppler ultrasound and SOPPG, the presence or absence of a hemodynamically significant lesion was accurately predicted in 235 (98%)."} {"id": "PMID:156096", "title": "Beneficial effects of pulsatile perfusion in the hypertrophied ventricle during ventricular fibrillation.", "content": "To assess the potential benefit of pulsatile perfusion inthe hypertrophied heart during fibrillation, 10 dogs with left ventricular hypertrophy, produced by previous supravalvular aortic banding, were used to compare linear and pulsatile perfusion in the fibrillating heart during total cardiopulmonary bypass. The mass spectrometer was used to measure subendocardial PCO2 and PO2 (PmCO2 and PmO2), and radioactive microspheres were utilized to measure myocardial blood flow in the same layers. Pulsatile perfusion was established using the recently develop \"bubble tubing,\" which produces a pulse pressure of at least 20 mm Hg and can be used in a standard roller-pump apparatus. Both linear and pulsatile flows were compared at mean aortic root pressures of 80 and 50 mm Hg, and these four combinations of aortic root pressure and type of flow were employed for periods of 30 minutes each. Myocardial ischemia developed during linear coronary perfusion at 50 mm Hg, as evidenced by an elevation of PmCO2. Ischemia was not evident during pulsatile perfusion at the same mean pressure. Reversal ischemia was a result of increased myocardial blood flow and pulsatile perfusion, and this increase was shown to occur maximally in the deeper subendocardial layer. Ischemia was not eviden during linear or pulsatile perfusion at an mean perfusion pressure 80 mm Hg. Thus, if lower perfusion pressures are to be tolerated in patients with left ventricular hypertrophy, pulsatile perfusion with the bubble tubing technique may prevent the development of subendocardial ischemia or infarction.", "contents": "Beneficial effects of pulsatile perfusion in the hypertrophied ventricle during ventricular fibrillation. To assess the potential benefit of pulsatile perfusion inthe hypertrophied heart during fibrillation, 10 dogs with left ventricular hypertrophy, produced by previous supravalvular aortic banding, were used to compare linear and pulsatile perfusion in the fibrillating heart during total cardiopulmonary bypass. The mass spectrometer was used to measure subendocardial PCO2 and PO2 (PmCO2 and PmO2), and radioactive microspheres were utilized to measure myocardial blood flow in the same layers. Pulsatile perfusion was established using the recently develop \"bubble tubing,\" which produces a pulse pressure of at least 20 mm Hg and can be used in a standard roller-pump apparatus. Both linear and pulsatile flows were compared at mean aortic root pressures of 80 and 50 mm Hg, and these four combinations of aortic root pressure and type of flow were employed for periods of 30 minutes each. Myocardial ischemia developed during linear coronary perfusion at 50 mm Hg, as evidenced by an elevation of PmCO2. Ischemia was not evident during pulsatile perfusion at the same mean pressure. Reversal ischemia was a result of increased myocardial blood flow and pulsatile perfusion, and this increase was shown to occur maximally in the deeper subendocardial layer. Ischemia was not eviden during linear or pulsatile perfusion at an mean perfusion pressure 80 mm Hg. Thus, if lower perfusion pressures are to be tolerated in patients with left ventricular hypertrophy, pulsatile perfusion with the bubble tubing technique may prevent the development of subendocardial ischemia or infarction."} {"id": "PMID:156097", "title": "Identification of keratan sulfate in liver affected by Morquio syndrome.", "content": "Glycosaminoglycan content, composition and molecular weight were determined in liver obtained from a patient with Morquio syndrome (Mucopolysaccharidosis IV). There was about a four-fold increase in glycosaminoglycan content (as hexosamine) of the affected liver as compared to the control liver. The major glycosaminoglycan accumulated in the liver was keratan sulfate, which was not found in the control liver. Chondroitin sulfates, especially chondroitin 6-sulfate, were also increased. Heparan sulfate isolated from the liver of a patient with Morquio syndrome was structurally different to that from control liver, and the glycosaminoglycans from Morquio syndrome were of a much lower molecular weight than those from control.", "contents": "Identification of keratan sulfate in liver affected by Morquio syndrome. Glycosaminoglycan content, composition and molecular weight were determined in liver obtained from a patient with Morquio syndrome (Mucopolysaccharidosis IV). There was about a four-fold increase in glycosaminoglycan content (as hexosamine) of the affected liver as compared to the control liver. The major glycosaminoglycan accumulated in the liver was keratan sulfate, which was not found in the control liver. Chondroitin sulfates, especially chondroitin 6-sulfate, were also increased. Heparan sulfate isolated from the liver of a patient with Morquio syndrome was structurally different to that from control liver, and the glycosaminoglycans from Morquio syndrome were of a much lower molecular weight than those from control."} {"id": "PMID:156105", "title": "Racial and sexual differences in the standard electrocardiogram of black vs white adolescents.", "content": "Standard 12-lead electrocardiograms were recorded in 114 healthy adolescents to substantiate possible influences of race and sex on the \"juvenile pattern\" (increased precordial voltages of QRS complex, precordial T wave inversions, and ST-segment elevations considered pathologic in adults) in this age group. Black male subjects had the highest precordial QRS amplitudes and the highest incidence of biphasic or negative precordial T waves and ST-segment deviations. In white male subjects, these findings were less pronounced but were more evident than in black or white female subjects. Results indicate the following: (1) race-specific and sex-specific normal electrocardiographic standards should be developed in adolescents; (2) criteria for left ventricular hypertrophy are race-specific and sex-specific and should be tested against independent anatomic or physiologic information in adolescents with left ventricular overload; and (3) the \"juvenile pattern\" may be viewed as a predictable continuum of age-related changes starting in childhood and progressing through adolescence on to later life.", "contents": "Racial and sexual differences in the standard electrocardiogram of black vs white adolescents. Standard 12-lead electrocardiograms were recorded in 114 healthy adolescents to substantiate possible influences of race and sex on the \"juvenile pattern\" (increased precordial voltages of QRS complex, precordial T wave inversions, and ST-segment elevations considered pathologic in adults) in this age group. Black male subjects had the highest precordial QRS amplitudes and the highest incidence of biphasic or negative precordial T waves and ST-segment deviations. In white male subjects, these findings were less pronounced but were more evident than in black or white female subjects. Results indicate the following: (1) race-specific and sex-specific normal electrocardiographic standards should be developed in adolescents; (2) criteria for left ventricular hypertrophy are race-specific and sex-specific and should be tested against independent anatomic or physiologic information in adolescents with left ventricular overload; and (3) the \"juvenile pattern\" may be viewed as a predictable continuum of age-related changes starting in childhood and progressing through adolescence on to later life."} {"id": "PMID:156108", "title": "Atrial depolarization in Wolf-Parkinson-White and Lown-Ganong-Levine syndrome: vectorcardiographic features.", "content": "The atrial depolarization pattern was studied in 22 patients with Wolff-Parkinson-White and Lown-Ganong-Levine syndrome. The influence of the accessory pathways on the shape, magnitude and conduction pattern of the PSE loop was analyzed. An accurate evaluation of the beginning of the delta wave and of the P loop distortions was obtained by using high magnification (1 mV = 30 cm) recordings. The Frank lead system was used. The influence of atrial size (documented by echocardiography) on the PSE loop is emphasized. Special attention has been focused on the terminal vectors as compared to a control group. In Wolff-Parkinson-White syndrome the size of the PSE loop was smaller than in Lown-Ganong-Levine syndrome or in the normal group. When atrial conduction disturbances and/or atrial enlargement was present the PSE loop was larger and distorted. The terminal vectors were abnormally oriented in 75 percent of the patients with Wolff-Parkinson-White syndrome, but only in one with Lown-Ganong-Levine syndrome. The beginning of the delta wave in patients with Wolff-Parkinson-White syndrome was located to the left of the E point in all but two. When the \"concertina\" effect was present, the direction of the terminal vectors remained unchanged. In four patients with the Lown-Ganong-Levine syndrome, the PSE loop closed, and in three patients, a small opening was present. We suggest that the changes in contour, duration and amplitude of the PSE loop are due to an abnormal pattern of atrial depolorization in Wolff-Parkinson-White syndrome.", "contents": "Atrial depolarization in Wolf-Parkinson-White and Lown-Ganong-Levine syndrome: vectorcardiographic features. The atrial depolarization pattern was studied in 22 patients with Wolff-Parkinson-White and Lown-Ganong-Levine syndrome. The influence of the accessory pathways on the shape, magnitude and conduction pattern of the PSE loop was analyzed. An accurate evaluation of the beginning of the delta wave and of the P loop distortions was obtained by using high magnification (1 mV = 30 cm) recordings. The Frank lead system was used. The influence of atrial size (documented by echocardiography) on the PSE loop is emphasized. Special attention has been focused on the terminal vectors as compared to a control group. In Wolff-Parkinson-White syndrome the size of the PSE loop was smaller than in Lown-Ganong-Levine syndrome or in the normal group. When atrial conduction disturbances and/or atrial enlargement was present the PSE loop was larger and distorted. The terminal vectors were abnormally oriented in 75 percent of the patients with Wolff-Parkinson-White syndrome, but only in one with Lown-Ganong-Levine syndrome. The beginning of the delta wave in patients with Wolff-Parkinson-White syndrome was located to the left of the E point in all but two. When the \"concertina\" effect was present, the direction of the terminal vectors remained unchanged. In four patients with the Lown-Ganong-Levine syndrome, the PSE loop closed, and in three patients, a small opening was present. We suggest that the changes in contour, duration and amplitude of the PSE loop are due to an abnormal pattern of atrial depolorization in Wolff-Parkinson-White syndrome."} {"id": "PMID:156109", "title": "Effects of platinum antitumor agents on in vitro assays of human antitumor immunity. I. Effects of cis-[pt (NH3)2Cl2] on the mixed lymphocyte tumor assay.", "content": "Human lymphoblast cell lines (LCL) were treated with the antitumor complex Cis-[pt(NH3)2Cl2] (CPDC). Direct effects of CPDC treatment on LCL growth, as well as on LCL recognition by human lymphocytes in vitro are reported. Treatment of LCL with 10 micro m CPDC strongly inhibits DNA and protein synthesis, but has little effect on LCL viability. At this concentration, CPDC also inhibits the proliferation of human peripheral blood lymphocytes (PBL) in response to mitogens or allogeneic cells. Therefore, studies of LCL recognition by human PBL were conducted using CPDC pretreated and extensively washed LCL. Recognition of CPDC pretreated LCL in the in vitro mixed lymphocyte tumor (MLT) cell assay for the activation phase of cellular immunity is reduced. The decrease in MLT response is not due to direct effects of the complex on the responding T lymphocytes, but may be due to lowered antigen expression of treated LCL or other mechanisms. If CPDC does enhance tumor rejection in vivo, it does not appear to be due to enhanced recognition by T cells.", "contents": "Effects of platinum antitumor agents on in vitro assays of human antitumor immunity. I. Effects of cis-[pt (NH3)2Cl2] on the mixed lymphocyte tumor assay. Human lymphoblast cell lines (LCL) were treated with the antitumor complex Cis-[pt(NH3)2Cl2] (CPDC). Direct effects of CPDC treatment on LCL growth, as well as on LCL recognition by human lymphocytes in vitro are reported. Treatment of LCL with 10 micro m CPDC strongly inhibits DNA and protein synthesis, but has little effect on LCL viability. At this concentration, CPDC also inhibits the proliferation of human peripheral blood lymphocytes (PBL) in response to mitogens or allogeneic cells. Therefore, studies of LCL recognition by human PBL were conducted using CPDC pretreated and extensively washed LCL. Recognition of CPDC pretreated LCL in the in vitro mixed lymphocyte tumor (MLT) cell assay for the activation phase of cellular immunity is reduced. The decrease in MLT response is not due to direct effects of the complex on the responding T lymphocytes, but may be due to lowered antigen expression of treated LCL or other mechanisms. If CPDC does enhance tumor rejection in vivo, it does not appear to be due to enhanced recognition by T cells."} {"id": "PMID:156110", "title": "Studies on the mode of action of 5-fluorocytosine in Aspergillus species.", "content": "The mode of action of 5-fluorocytosine (5-FC) was studied in three isolates of pathogenic Aspergillus with varying degrees of susceptibility to the drug. Distribution studies showed that susceptibility or resistance to 5-FC was not dependent on uptake of the drug. While only a small percentage of the total 5-FC taken up was found in the RNA fraction of the cells, most remained in the acid-soluble intracellular pool. 5-FC, 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine monophosphate (5-Fd-UMP) were among metabolites identified in the pool. In addition, fluoroorotic acid appeared to be a major constituent of the metabolites derived from 5-FC. The aspergilli also were capable of utilizing cytosine as a nitrogen source and this is suggested as a possible mechanism of resistance. A dual mode of action for 5-FC in the aspergilli is proposed. This consists of, first, incorporation of 5-FU into RNA and, second, inhibition of DNA synthesis by production of 5-FdUMP.", "contents": "Studies on the mode of action of 5-fluorocytosine in Aspergillus species. The mode of action of 5-fluorocytosine (5-FC) was studied in three isolates of pathogenic Aspergillus with varying degrees of susceptibility to the drug. Distribution studies showed that susceptibility or resistance to 5-FC was not dependent on uptake of the drug. While only a small percentage of the total 5-FC taken up was found in the RNA fraction of the cells, most remained in the acid-soluble intracellular pool. 5-FC, 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine monophosphate (5-Fd-UMP) were among metabolites identified in the pool. In addition, fluoroorotic acid appeared to be a major constituent of the metabolites derived from 5-FC. The aspergilli also were capable of utilizing cytosine as a nitrogen source and this is suggested as a possible mechanism of resistance. A dual mode of action for 5-FC in the aspergilli is proposed. This consists of, first, incorporation of 5-FU into RNA and, second, inhibition of DNA synthesis by production of 5-FdUMP."} {"id": "PMID:156111", "title": "[Changes in allogeneic immune response of swine in the course of a liver allograft].", "content": "Pig liver allografts showed a typical rejection crisis. The degree of rejection depended on the SLA-typing. Despite SLA-incompatibility pig liver allografts can be tolerated. Short-term survivors showed an immunological hyporeactivity. Long-term survivors reconstituted their cellular immune-reactions and developed an antibody which appeared to function as an antigen-antibody-complex or an anti-Ia-antibody.", "contents": "[Changes in allogeneic immune response of swine in the course of a liver allograft]. Pig liver allografts showed a typical rejection crisis. The degree of rejection depended on the SLA-typing. Despite SLA-incompatibility pig liver allografts can be tolerated. Short-term survivors showed an immunological hyporeactivity. Long-term survivors reconstituted their cellular immune-reactions and developed an antibody which appeared to function as an antigen-antibody-complex or an anti-Ia-antibody."} {"id": "PMID:156112", "title": "[Evidence of a specific defect in effector cell formation following kidney and liver allotransplants in humans].", "content": "In 5 recipients of cadaver kidney allografts and 1 patient with an orthotopic liver transplant specific in vitro reactivity of blood lymphocytes against donor antigens was monitored by means of the unilateral MLC assay and an indirect cytotoxicity assay (using MLC activated recipient lymphocytes as effector cells in a 51Cr release assay). The liver patient and 3 of the kidney graft recipients developed a specific defect in the capability to generate cytotoxic effector cells in vitro. Proliferative reactivity against donor lymphocytes was retained in these patients.", "contents": "[Evidence of a specific defect in effector cell formation following kidney and liver allotransplants in humans]. In 5 recipients of cadaver kidney allografts and 1 patient with an orthotopic liver transplant specific in vitro reactivity of blood lymphocytes against donor antigens was monitored by means of the unilateral MLC assay and an indirect cytotoxicity assay (using MLC activated recipient lymphocytes as effector cells in a 51Cr release assay). The liver patient and 3 of the kidney graft recipients developed a specific defect in the capability to generate cytotoxic effector cells in vitro. Proliferative reactivity against donor lymphocytes was retained in these patients."} {"id": "PMID:156115", "title": "[Regression of left ventricular hypertophy in the ECG during antihypertensive treatment: preliminary observations (author's transl)].", "content": "Typical signs of left ventricular hypertrophy (LVH) were present in the ECG of 36 (10 women, 26 men) of 127 persons with essential hypertension (46 women, 81 men). After a two-year course of combined drug treatment (chlortalidone, reserpine, methyl-dopa, hydralazine) with effective blood-pressure reduction LVH was still present in the ECG of 29, after a four-year course of only 15 among 36, i. e. a reduction in the presence of LVH of nearly 60%. Since the patients' body-weight remained unchanged during this period, the regression in ECG changes is ascribed to the effectiveness of the drug treatment.", "contents": "[Regression of left ventricular hypertophy in the ECG during antihypertensive treatment: preliminary observations (author's transl)]. Typical signs of left ventricular hypertrophy (LVH) were present in the ECG of 36 (10 women, 26 men) of 127 persons with essential hypertension (46 women, 81 men). After a two-year course of combined drug treatment (chlortalidone, reserpine, methyl-dopa, hydralazine) with effective blood-pressure reduction LVH was still present in the ECG of 29, after a four-year course of only 15 among 36, i. e. a reduction in the presence of LVH of nearly 60%. Since the patients' body-weight remained unchanged during this period, the regression in ECG changes is ascribed to the effectiveness of the drug treatment."} {"id": "PMID:156117", "title": "Statistical survey of gynecological laparoscopy/pelviscopy in Germany till 1977.", "content": "By mailing, 1.365 questionnaires to gynecologists, 265,900 laparoscopies/pelviscopies were reported in 682 questionnaires (49.2%) by anonymous answer. These had been performed by 380 gynecologists (hospitals) between 1949 and 1977 in Germany. 302 gynecologists who answered the questionnaires (44.2%) are not using the endoscopic technique. Till the end of 1977 in Germany monopolar high-frequency current was used in 52%, bipolar high-frequency current was used in 42%, and modern endocoagulation was used in 25% for the purposes of hemostasis. 240 hospitals (63%) are mainly using pelviscopes of 5--8 mm diameter, 124 hospitals (33%) are using laparoscopes of 11 mm diameter. All together 949 (3.56%) complications had occurred which necessitated 690 laparotomies (2.59%). Cause of these complications were damages to vessels and burns by high-frequency current. 24 (0,09%) deaths were reported which had occurred during or following the intervention, that is one death for 11,000 pelviscopies. Mortality due to this method can be itemized as follows: 13 deaths (0.09%) in 140,977 (53%) diagnostical laparoscopies/pelviscopies, 3 deaths (0.08%) in 37,639 (14.2%) diagnostical-operative pelviscopies, 8 deaths (0.09%) in 87,284 (32.8%) sterilizations. Since 1974, however, the mortality rate is smaller than 1 : 100,000. Since 1973 every year 30,000 to 35,000 pelviscopies were registered in Germany; no deaths in 1974, 1976 and 1977.", "contents": "Statistical survey of gynecological laparoscopy/pelviscopy in Germany till 1977. By mailing, 1.365 questionnaires to gynecologists, 265,900 laparoscopies/pelviscopies were reported in 682 questionnaires (49.2%) by anonymous answer. These had been performed by 380 gynecologists (hospitals) between 1949 and 1977 in Germany. 302 gynecologists who answered the questionnaires (44.2%) are not using the endoscopic technique. Till the end of 1977 in Germany monopolar high-frequency current was used in 52%, bipolar high-frequency current was used in 42%, and modern endocoagulation was used in 25% for the purposes of hemostasis. 240 hospitals (63%) are mainly using pelviscopes of 5--8 mm diameter, 124 hospitals (33%) are using laparoscopes of 11 mm diameter. All together 949 (3.56%) complications had occurred which necessitated 690 laparotomies (2.59%). Cause of these complications were damages to vessels and burns by high-frequency current. 24 (0,09%) deaths were reported which had occurred during or following the intervention, that is one death for 11,000 pelviscopies. Mortality due to this method can be itemized as follows: 13 deaths (0.09%) in 140,977 (53%) diagnostical laparoscopies/pelviscopies, 3 deaths (0.08%) in 37,639 (14.2%) diagnostical-operative pelviscopies, 8 deaths (0.09%) in 87,284 (32.8%) sterilizations. Since 1974, however, the mortality rate is smaller than 1 : 100,000. Since 1973 every year 30,000 to 35,000 pelviscopies were registered in Germany; no deaths in 1974, 1976 and 1977."} {"id": "PMID:156118", "title": "New methods of pelviscopy (gynecologic laparoscopy) for myomectomy, ovariectomy, tubectomy and adnectomy.", "content": "The development of suitable instruments for perfect grasping, cutting, sucking, ligating and of a new system of performing hemostasis by endocoagulation through a 7--11 mm phi trocar-sheath enables us to initiate effective endoscopical intraabdominal surgery. New surgical techniques are being investigated on greater than 2.000 cases of surgical pelviscopic interventions which were performed between 1973--1976. Since 1977 we have extended the endoscopical intraabdominal surgery as follows: Myomectomy (subserous), adnectomy, ovarian-cyst-resection, cystomectomy, tubectomy in case of tubal pregnancy. In 115 cases no intra- or postoperative complications have occurred. Normal postsurgical healing procedure could be checked on 18 re-pelviscopies and on 2 later laparotomies. The new technical equipment has opened us together with special surgical procedures a new era of gynecologic surgery.", "contents": "New methods of pelviscopy (gynecologic laparoscopy) for myomectomy, ovariectomy, tubectomy and adnectomy. The development of suitable instruments for perfect grasping, cutting, sucking, ligating and of a new system of performing hemostasis by endocoagulation through a 7--11 mm phi trocar-sheath enables us to initiate effective endoscopical intraabdominal surgery. New surgical techniques are being investigated on greater than 2.000 cases of surgical pelviscopic interventions which were performed between 1973--1976. Since 1977 we have extended the endoscopical intraabdominal surgery as follows: Myomectomy (subserous), adnectomy, ovarian-cyst-resection, cystomectomy, tubectomy in case of tubal pregnancy. In 115 cases no intra- or postoperative complications have occurred. Normal postsurgical healing procedure could be checked on 18 re-pelviscopies and on 2 later laparotomies. The new technical equipment has opened us together with special surgical procedures a new era of gynecologic surgery."} {"id": "PMID:156119", "title": "Immune depression in trypanosome-infected mice. II. Characterization of the spleen cell types involved.", "content": "Spleen cells from Trypanosoma congolense-infected mice showed a drastic depression in their capacity to respond to B and T lymphocyte mitogens and to allogeneic spleen cells in mixed lymphocyte cultures. Spleen cells from infected mice were also poor stimulators in mixed lymphocyte cultures. The poor responsiveness or stimulation capacity was not due simply to dilution of relevant B or T lymphocytes by the large number of null cells found in the spleens of infected animals. These null cells expressed approximately eight times more H-2 antigen than spleen cells from normal (uninfected) mice and were devoid of Ia antigens.", "contents": "Immune depression in trypanosome-infected mice. II. Characterization of the spleen cell types involved. Spleen cells from Trypanosoma congolense-infected mice showed a drastic depression in their capacity to respond to B and T lymphocyte mitogens and to allogeneic spleen cells in mixed lymphocyte cultures. Spleen cells from infected mice were also poor stimulators in mixed lymphocyte cultures. The poor responsiveness or stimulation capacity was not due simply to dilution of relevant B or T lymphocytes by the large number of null cells found in the spleens of infected animals. These null cells expressed approximately eight times more H-2 antigen than spleen cells from normal (uninfected) mice and were devoid of Ia antigens."} {"id": "PMID:156120", "title": "Immune depression in trypanosome-infected mice. III. suppressor cells.", "content": "Spleen cells from trypanosome-infected mice strongly suppressed lymphocyte stimulation induced in normal spleen cell populations by lipopolysaccharide, concanavalin A or allogeneic (H-2-different) stimulator cells. This suppression was not H-2-restricted, as responses of spleen lymphocytes both allogeneic and syngeneic to the suppressors were inhibited. Irradiation or mitomycin C treatment of suppressor populations markedly reduced but did not eliminate suppressor activity. Suppressor populations were effective when present in very low numbers. Addition of suppressor cells to mixed lymphocyte cultures at various intervals after initiation of the cultures showed that the suppressors require 48 h to manifest their activity. Cell depletion or enrichment experiments indicate that the mechanism of suppression is complex and involves more than one cell type.", "contents": "Immune depression in trypanosome-infected mice. III. suppressor cells. Spleen cells from trypanosome-infected mice strongly suppressed lymphocyte stimulation induced in normal spleen cell populations by lipopolysaccharide, concanavalin A or allogeneic (H-2-different) stimulator cells. This suppression was not H-2-restricted, as responses of spleen lymphocytes both allogeneic and syngeneic to the suppressors were inhibited. Irradiation or mitomycin C treatment of suppressor populations markedly reduced but did not eliminate suppressor activity. Suppressor populations were effective when present in very low numbers. Addition of suppressor cells to mixed lymphocyte cultures at various intervals after initiation of the cultures showed that the suppressors require 48 h to manifest their activity. Cell depletion or enrichment experiments indicate that the mechanism of suppression is complex and involves more than one cell type."} {"id": "PMID:156124", "title": "A histochemical study of denervated marsupial hemidiaphragm.", "content": "The marsupial (quokka) hemidiaphragm showed postdenervation hypertrophy and subsequent atrophy. The type II muscle fibres hypertrophied up to 20 days postoperation and then regressed. However, the type I fibres hypertrophied throughout the experimental period (100 days) studied. Unlike denervated eutherian hemidiaphragm, fibre-splitting was absent in the denervated marsupial muscle. An enhancement of the ATPase reaction in the denervated type I fibres may be due to dedifferentiation. Presumably innervation exerts a 'negative control' and prevents increase of type I fibre size in the normal hemidiaphragm.", "contents": "A histochemical study of denervated marsupial hemidiaphragm. The marsupial (quokka) hemidiaphragm showed postdenervation hypertrophy and subsequent atrophy. The type II muscle fibres hypertrophied up to 20 days postoperation and then regressed. However, the type I fibres hypertrophied throughout the experimental period (100 days) studied. Unlike denervated eutherian hemidiaphragm, fibre-splitting was absent in the denervated marsupial muscle. An enhancement of the ATPase reaction in the denervated type I fibres may be due to dedifferentiation. Presumably innervation exerts a 'negative control' and prevents increase of type I fibre size in the normal hemidiaphragm."} {"id": "PMID:156125", "title": "[Action of polymethylene-bis-quaternary compounds on the muscarinic and nicotinic cholinoreceptors].", "content": "The action of compounds with general formula (formula: see text) on the frog heart ventricle, cat blood pressure, guinea pig ileum and frog rectus abdominis was studied. With dioxolane radicals (type F-2268) a strong muscarinomimetic action on the cat arterial blood pressure and guinea pig ileum was observed, with maximum marked action at n = 10, which was more pronounced at an even than at odd number of methylene groups. On the frog heart the compounds with an odd number of \"n\" elicited an atropine-like action. The compounds with pentyl radicals produced no effect on blood pressure and a weak cholinolytic effect on the frog heart. On the ileum they exhibited a cholinomimetic effect. All compounds studied acted as noncompetitive cholinolytics on the frog rectus.", "contents": "[Action of polymethylene-bis-quaternary compounds on the muscarinic and nicotinic cholinoreceptors]. The action of compounds with general formula (formula: see text) on the frog heart ventricle, cat blood pressure, guinea pig ileum and frog rectus abdominis was studied. With dioxolane radicals (type F-2268) a strong muscarinomimetic action on the cat arterial blood pressure and guinea pig ileum was observed, with maximum marked action at n = 10, which was more pronounced at an even than at odd number of methylene groups. On the frog heart the compounds with an odd number of \"n\" elicited an atropine-like action. The compounds with pentyl radicals produced no effect on blood pressure and a weak cholinolytic effect on the frog heart. On the ileum they exhibited a cholinomimetic effect. All compounds studied acted as noncompetitive cholinolytics on the frog rectus."} {"id": "PMID:156132", "title": "Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease.", "content": "We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute.", "contents": "Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease. We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute."} {"id": "PMID:156133", "title": "Menstrual patterns and women's attitudes following sterilization by Falope rings.", "content": "Follow-up data on 147 women sterilized by laparoscopic Falope ring application were analyzed for changes in menstrual patterns, postoperative complications, patient feelings about surgery, and incidence of regret. Twelve to twenty-eight months after surgery, there were no consistent changes in interval, length, or amount of menstrual flow, and only 4% of women developed transient episodes of dysfunctional uterine bleeding. Analysis of feelings after sterilization showed that 90% of women were satisfied with the sterilization, 3% were unhappy, and 7% were ambivalent. Feelings of regret were not associated with postoperative complications and appeared to be related to the reasons for sterilization. Individual counseling not only helped to identify the population at risk for regret but also served to reduce the incidence of poststerilization ambivalent feelings.", "contents": "Menstrual patterns and women's attitudes following sterilization by Falope rings. Follow-up data on 147 women sterilized by laparoscopic Falope ring application were analyzed for changes in menstrual patterns, postoperative complications, patient feelings about surgery, and incidence of regret. Twelve to twenty-eight months after surgery, there were no consistent changes in interval, length, or amount of menstrual flow, and only 4% of women developed transient episodes of dysfunctional uterine bleeding. Analysis of feelings after sterilization showed that 90% of women were satisfied with the sterilization, 3% were unhappy, and 7% were ambivalent. Feelings of regret were not associated with postoperative complications and appeared to be related to the reasons for sterilization. Individual counseling not only helped to identify the population at risk for regret but also served to reduce the incidence of poststerilization ambivalent feelings."} {"id": "PMID:156137", "title": "Erythroid differentiation and poly(ADP-ribose) synthesis in Friend leukemia cells.", "content": "Nicotinamide, a specific inhibitor of poly(ADP-ribose) synthetase, was found to be a moderate inducer of hemoglobin synthesis in Friend erythroid leukemia cells (FLC). Therefore, the effect of other inducers, s-ch as dimethyl sulfoxide (DMSO), hexamethylene-bisacetamide (HMBA), and butyrate, on poly(ADP-ribose) synthesis was examined. The extent of poly(ADP-ribose) synthesis in nuclei of FLC treated with DMSO or HMBA began to decrease before many phenotypic changes including hemoglobin production and reached 30--50% of the level of nontreated control when the cells enter the stationary phase. FLC variants unresponsive to HMBA or DMSO did not exhibit as low an activity of poly(ADP-ribose) synthesis as their parent cells did by treatment with these inducers. In contrast, butyrate stimulated poly(ADP-ribose) synthesis transiently but distinctly (about 50%) at an early stage of culture (6--24 hr), but suppressed it at a later stage. Neither the cell growth nor degradation of poly(ADP-ribose) is correlated with the effect of inducers. These results suggest that the level of poly(ADP-ribose) synthesis is correlated with the differentiation of FLC.", "contents": "Erythroid differentiation and poly(ADP-ribose) synthesis in Friend leukemia cells. Nicotinamide, a specific inhibitor of poly(ADP-ribose) synthetase, was found to be a moderate inducer of hemoglobin synthesis in Friend erythroid leukemia cells (FLC). Therefore, the effect of other inducers, s-ch as dimethyl sulfoxide (DMSO), hexamethylene-bisacetamide (HMBA), and butyrate, on poly(ADP-ribose) synthesis was examined. The extent of poly(ADP-ribose) synthesis in nuclei of FLC treated with DMSO or HMBA began to decrease before many phenotypic changes including hemoglobin production and reached 30--50% of the level of nontreated control when the cells enter the stationary phase. FLC variants unresponsive to HMBA or DMSO did not exhibit as low an activity of poly(ADP-ribose) synthesis as their parent cells did by treatment with these inducers. In contrast, butyrate stimulated poly(ADP-ribose) synthesis transiently but distinctly (about 50%) at an early stage of culture (6--24 hr), but suppressed it at a later stage. Neither the cell growth nor degradation of poly(ADP-ribose) is correlated with the effect of inducers. These results suggest that the level of poly(ADP-ribose) synthesis is correlated with the differentiation of FLC."} {"id": "PMID:156139", "title": "Echocardiography: a diagnostic plus.", "content": "Echocardiography adds a new dimension to diagnosis of cardiac disorders. This safe, noninvasive technique aids in the differential diagnosis of systolic murmur, chest pain, and cardiomegaly, in the etiologic diagnosis of mitral regurgitation and atrial fibrillation, and in assessing left ventricular function.", "contents": "Echocardiography: a diagnostic plus. Echocardiography adds a new dimension to diagnosis of cardiac disorders. This safe, noninvasive technique aids in the differential diagnosis of systolic murmur, chest pain, and cardiomegaly, in the etiologic diagnosis of mitral regurgitation and atrial fibrillation, and in assessing left ventricular function."} {"id": "PMID:156143", "title": "Pyemotes herfsi (Oudemans, 1936) as causative agent of another mass dermatitis in Europe (Acari, Pyemotidae).", "content": "The authors describe new cases of human dermatitis caused by Pyemotes herfsi occurring in the food mixing shed for the farrowing house in the piggery at a farm in the destrict of Olomouc, where seven persons handling feedstuff were infected. The disease became manifest as a papular rash, appearing particularly on the back, and all over the body except on the hands and face. When the afflicted person discontinued work in the feed mixing shed, the rash disappeared quickly. The mites were found in the granular dust accumulated in the loft above the food mixing shed. The initial host (insects) could not be identified. After cleaning and disinsecting the contaminated premises with Metation E 50 the workers were free from any symptoms. The mites of the genus Pyemotes, particularly the species P. herfsi (Oudemans, 1936) are little known, but probably frequent causative agents of human dermatitides.", "contents": "Pyemotes herfsi (Oudemans, 1936) as causative agent of another mass dermatitis in Europe (Acari, Pyemotidae). The authors describe new cases of human dermatitis caused by Pyemotes herfsi occurring in the food mixing shed for the farrowing house in the piggery at a farm in the destrict of Olomouc, where seven persons handling feedstuff were infected. The disease became manifest as a papular rash, appearing particularly on the back, and all over the body except on the hands and face. When the afflicted person discontinued work in the feed mixing shed, the rash disappeared quickly. The mites were found in the granular dust accumulated in the loft above the food mixing shed. The initial host (insects) could not be identified. After cleaning and disinsecting the contaminated premises with Metation E 50 the workers were free from any symptoms. The mites of the genus Pyemotes, particularly the species P. herfsi (Oudemans, 1936) are little known, but probably frequent causative agents of human dermatitides."} {"id": "PMID:156144", "title": "[Hormonal regulation and hormone therapy in childhood and adolescence. Part 2: Therapeutic problems (tall stature, amenorrhea, delayed puberty, oligomenorrhea, precocious puberty, anorexia nervosa, anisomastia, hypermastia, acne etc)].", "content": "The most important therapeutic problems of female puberty and adolescence are discussed, including high stature, amenorrhoea, oligomenorrhea, pubertas tarda, anovulation, anorexia, anisomastia, hypermastia. Indications for treatment are given and the possibilities for a prophylactic medicine in this age group are stressed.", "contents": "[Hormonal regulation and hormone therapy in childhood and adolescence. Part 2: Therapeutic problems (tall stature, amenorrhea, delayed puberty, oligomenorrhea, precocious puberty, anorexia nervosa, anisomastia, hypermastia, acne etc)]. The most important therapeutic problems of female puberty and adolescence are discussed, including high stature, amenorrhoea, oligomenorrhea, pubertas tarda, anovulation, anorexia, anisomastia, hypermastia. Indications for treatment are given and the possibilities for a prophylactic medicine in this age group are stressed."} {"id": "PMID:156145", "title": "[Vascular reconstruction in the aorto-iliac region. Lowered mortality with an extraperitoneal approach].", "content": "From 1962 to 1978 1938 reconstructions because of arterial occlusive disease were performed at the Department of Surgery, St\u00e4dt. Klinikum Karlsruhe. Of these 297 were primary aorto-iliac reconstructions. All latter cases were classified according to morphologic characteristics. The ratio of men to women was 8 : 1, the average age 58,9 years. A comparison of the results in these 227 patients with reconstruction either by endarteriectomy or dacron bypass was made regarding the way of incision. The results show a lower letality of 4,6% when extraperitoneal exposition is used compared to 14,1% when transperitoneal exposition was performed. As there was no difference found in the late results after either method of reconstruction (123 patients were reexamined), extraperitoneal exposition is preferred except in cases with aneurysm and aortic occlusion up to the renal arteries.", "contents": "[Vascular reconstruction in the aorto-iliac region. Lowered mortality with an extraperitoneal approach]. From 1962 to 1978 1938 reconstructions because of arterial occlusive disease were performed at the Department of Surgery, St\u00e4dt. Klinikum Karlsruhe. Of these 297 were primary aorto-iliac reconstructions. All latter cases were classified according to morphologic characteristics. The ratio of men to women was 8 : 1, the average age 58,9 years. A comparison of the results in these 227 patients with reconstruction either by endarteriectomy or dacron bypass was made regarding the way of incision. The results show a lower letality of 4,6% when extraperitoneal exposition is used compared to 14,1% when transperitoneal exposition was performed. As there was no difference found in the late results after either method of reconstruction (123 patients were reexamined), extraperitoneal exposition is preferred except in cases with aneurysm and aortic occlusion up to the renal arteries."} {"id": "PMID:156161", "title": "Loss of lymphocyte chalone activity in mice with autoimmune disease.", "content": "Lymphocyte chalone from the spleens of old BALB/c, young BALB/c and young NZB mice caused significant suppression of the proliferative response of BALB/c and NZB spleen cells to T and B mitogens, whereas lymphocyte chalone from old NZB spleen did not suppress. Lymphocyte chalone from young and old NZB mice was tested using different ages of NZB/NZW responding spleen cells; at all ages concanavalin A- and lipopolysaccharide-induced proliferation was suppressed less by the chalone from old NZB mice than from that of young NZB mice. The responding NZB/NZW cells were suppressed equivalently at all ages studied. The basis for the loss of lymphocyte chalone activity in old NZB mice remains unknown; however, it appears likely that this event has a role in the disturbance of the negative feedback control system which contributes to NZB autoimmune disease.", "contents": "Loss of lymphocyte chalone activity in mice with autoimmune disease. Lymphocyte chalone from the spleens of old BALB/c, young BALB/c and young NZB mice caused significant suppression of the proliferative response of BALB/c and NZB spleen cells to T and B mitogens, whereas lymphocyte chalone from old NZB spleen did not suppress. Lymphocyte chalone from young and old NZB mice was tested using different ages of NZB/NZW responding spleen cells; at all ages concanavalin A- and lipopolysaccharide-induced proliferation was suppressed less by the chalone from old NZB mice than from that of young NZB mice. The responding NZB/NZW cells were suppressed equivalently at all ages studied. The basis for the loss of lymphocyte chalone activity in old NZB mice remains unknown; however, it appears likely that this event has a role in the disturbance of the negative feedback control system which contributes to NZB autoimmune disease."} {"id": "PMID:156162", "title": "Studies on the interference between the allergic reactions caused by different antigen-antibody systems.", "content": "Interference between two different in vivo antigen-antibody reactions which occurred simultaneously was studied in guinea pigs. Animals were presensitized with an aqueous fraction (CP) extracted from cells of Corynebacterium equi, strain KO-85. Skin reactions of the Arthus type elicited by the CP fraction inhibited passive cutaneous anaphylaxis (PCA) induced by bovine serum albumin (BSA) and rabbit anti-BSA serum. PCA reactions of the CP-sensitized animals were also inhibited upon simultaneous challenges of BSA and the CP as evidence by reduction of PCA titer of the anti-BSA serum.", "contents": "Studies on the interference between the allergic reactions caused by different antigen-antibody systems. Interference between two different in vivo antigen-antibody reactions which occurred simultaneously was studied in guinea pigs. Animals were presensitized with an aqueous fraction (CP) extracted from cells of Corynebacterium equi, strain KO-85. Skin reactions of the Arthus type elicited by the CP fraction inhibited passive cutaneous anaphylaxis (PCA) induced by bovine serum albumin (BSA) and rabbit anti-BSA serum. PCA reactions of the CP-sensitized animals were also inhibited upon simultaneous challenges of BSA and the CP as evidence by reduction of PCA titer of the anti-BSA serum."} {"id": "PMID:156166", "title": "[Therapeutic aspects of seborrhea oleosa and pityriasis simplex capillitii].", "content": "The treatment of seborrhoea oleosa capillitii should aim at inhibiting depletion of the sebaceous glands, lipid synthesis in the sebaceous gland and microbial lipolysis of the triglycerides in the scalp and hair lipids. The use of isopropyl alcohol as a vehicle in a hair tonic reduces sebum depletion. Coal tar and estrogens reduce the lipid synthesis in the sebaceous gland. The lipolysis can be inhibited by various surfactants, isopropyl alcohol, colloidal sulphur, selenium disulphide, Omadine MDS and benzoyl peroxide. In the treatment of pityriasis simplex capillitii (dandruff) one aims at achieving inhibition of mitosis in the epidermis and, if possible, an additional \"keratolytic\" effect. Inhibition of mitosis could be demonstrated for coal tar, corticosteroids, selenium disulphide, cadmium sulphide, Omadine MDS, Zn Omadine and ichthyol sodium. Colloidal sulphur, salicylic acid, Omadine MDS and various surfactants act \"keratolytically\".", "contents": "[Therapeutic aspects of seborrhea oleosa and pityriasis simplex capillitii]. The treatment of seborrhoea oleosa capillitii should aim at inhibiting depletion of the sebaceous glands, lipid synthesis in the sebaceous gland and microbial lipolysis of the triglycerides in the scalp and hair lipids. The use of isopropyl alcohol as a vehicle in a hair tonic reduces sebum depletion. Coal tar and estrogens reduce the lipid synthesis in the sebaceous gland. The lipolysis can be inhibited by various surfactants, isopropyl alcohol, colloidal sulphur, selenium disulphide, Omadine MDS and benzoyl peroxide. In the treatment of pityriasis simplex capillitii (dandruff) one aims at achieving inhibition of mitosis in the epidermis and, if possible, an additional \"keratolytic\" effect. Inhibition of mitosis could be demonstrated for coal tar, corticosteroids, selenium disulphide, cadmium sulphide, Omadine MDS, Zn Omadine and ichthyol sodium. Colloidal sulphur, salicylic acid, Omadine MDS and various surfactants act \"keratolytically\"."} {"id": "PMID:156167", "title": "[Differentiation of various Propionibacterium species from acne-vulgaris efflorescences].", "content": "Samples of pustules taken from 37 patients with acne (a. vulgaris, a. papulopustulosa, a. conglobata) were examined using different culture mediums for the growth of anaerobic to microaerophilic coryneforms. We identified 46 isolates of Propionibacteria which were tested according to their morphological, biochemical, serological, and phagelysotopic reactions. Three types of Propionibacteria were found: P. acnes (33), P. granulosum (11) and P. avidum (2). Nine samples showed P. acnes combined with P. avidum, four samples from patients with acne conglobata showed P. granulosum or P. avidum only. Tests from 37 patients are too limited to reach definite conclusions. We are not able to suggest any correlation between type and degree of clinical acne, and the isolated Propionibacteria. These data indicate that pustules from patients with acne of all clinical degrees can contain P. acnes as well as other anaerobic coryneforms. Therefore, other species of anaerobic bacteria, particularly those of the \"propionibacteria type\", should be included in any discussion about the aetiological factors of acne.", "contents": "[Differentiation of various Propionibacterium species from acne-vulgaris efflorescences]. Samples of pustules taken from 37 patients with acne (a. vulgaris, a. papulopustulosa, a. conglobata) were examined using different culture mediums for the growth of anaerobic to microaerophilic coryneforms. We identified 46 isolates of Propionibacteria which were tested according to their morphological, biochemical, serological, and phagelysotopic reactions. Three types of Propionibacteria were found: P. acnes (33), P. granulosum (11) and P. avidum (2). Nine samples showed P. acnes combined with P. avidum, four samples from patients with acne conglobata showed P. granulosum or P. avidum only. Tests from 37 patients are too limited to reach definite conclusions. We are not able to suggest any correlation between type and degree of clinical acne, and the isolated Propionibacteria. These data indicate that pustules from patients with acne of all clinical degrees can contain P. acnes as well as other anaerobic coryneforms. Therefore, other species of anaerobic bacteria, particularly those of the \"propionibacteria type\", should be included in any discussion about the aetiological factors of acne."} {"id": "PMID:156178", "title": "Comparison of inducible and constitutive kynureninases of Neurospora crassa.", "content": "Two types of kynureninase were isolated from Neurospora crassa IFO 6068. The formation of one of them, which was separated from the inducible kynureninase by DEAE-cellulose chromatography, was independent of the presence of tryptophan in the growth medium. Ouchterlony double-diffusion analysis and immunochemical titration indicated that the constitutive-type enzyme is immunologically different from the inducible enzyme. We confirmed by a selective assay method with antiserum that the addition of tryptophan to the medium does not affect the formation of one of the enzymes (constitutive-type). The constitutive kynureninase was purified approximately 650-fold and was free of the inducible enzyme as judged by analytical gel electrophoresis. The molecular weight and optimum pH values of both enzymes are very similar. However, the constitutive enzyme shows much higher activity and affinity for L-3-hydroxykynurenine than for L-kynurenine, suggesting that the enzyme functions biosynthetically as a 3-hydroxykynureninase. Constitutive kynureninase activities were widely found in all the fungi tested, whereas the inducible enzyme activity was not present in Mucor or Rhizopus species. The inducible enzymes of all the Neurospora strains examined were shown to be immunologically identical.", "contents": "Comparison of inducible and constitutive kynureninases of Neurospora crassa. Two types of kynureninase were isolated from Neurospora crassa IFO 6068. The formation of one of them, which was separated from the inducible kynureninase by DEAE-cellulose chromatography, was independent of the presence of tryptophan in the growth medium. Ouchterlony double-diffusion analysis and immunochemical titration indicated that the constitutive-type enzyme is immunologically different from the inducible enzyme. We confirmed by a selective assay method with antiserum that the addition of tryptophan to the medium does not affect the formation of one of the enzymes (constitutive-type). The constitutive kynureninase was purified approximately 650-fold and was free of the inducible enzyme as judged by analytical gel electrophoresis. The molecular weight and optimum pH values of both enzymes are very similar. However, the constitutive enzyme shows much higher activity and affinity for L-3-hydroxykynurenine than for L-kynurenine, suggesting that the enzyme functions biosynthetically as a 3-hydroxykynureninase. Constitutive kynureninase activities were widely found in all the fungi tested, whereas the inducible enzyme activity was not present in Mucor or Rhizopus species. The inducible enzymes of all the Neurospora strains examined were shown to be immunologically identical."} {"id": "PMID:156179", "title": "Effect of thymidine on poly(ADP-ribosyl)ation in vivo.", "content": "The addition of thymidine as well as nicotinamide to isolated nuclei resulted in a strong inhibition of poly(ADP-ribosyl)ation, whereas that of hydroxyurea and amethopterin has essentially no effect. The nuclei isolated from the cells immediately after release from thymidine synchronization exhibited a significantly increased activity of poly(ADP-ribosyl)ation. Thereafter, the fluctuation pattern of the activity of poly(ADP-ribosyl)ation in isolated nuclei during the cell cycle was essentially the same as in the case of hydroxyurea synchronization. The activity of poly(ADP-ribosyl)ation in isolated nuclei after treatment with thymidine in vivo increased with the treatment time. The time-dependent increase was also evident in the case of nicotinamide treatment. Little increase in the activity was observed in hydroxyurea and amethopterin treatment. When poly(ADP-ribose) polymerase was extracted from the nuclei isolated from the cells which were pretreated with each of the four compounds, there was no significant difference in the amount among these compounds. The reason for the increase in the poly(ADP-ribosyl)ation in vitro by the in vivo treatment with thymidine is discussed.", "contents": "Effect of thymidine on poly(ADP-ribosyl)ation in vivo. The addition of thymidine as well as nicotinamide to isolated nuclei resulted in a strong inhibition of poly(ADP-ribosyl)ation, whereas that of hydroxyurea and amethopterin has essentially no effect. The nuclei isolated from the cells immediately after release from thymidine synchronization exhibited a significantly increased activity of poly(ADP-ribosyl)ation. Thereafter, the fluctuation pattern of the activity of poly(ADP-ribosyl)ation in isolated nuclei during the cell cycle was essentially the same as in the case of hydroxyurea synchronization. The activity of poly(ADP-ribosyl)ation in isolated nuclei after treatment with thymidine in vivo increased with the treatment time. The time-dependent increase was also evident in the case of nicotinamide treatment. Little increase in the activity was observed in hydroxyurea and amethopterin treatment. When poly(ADP-ribose) polymerase was extracted from the nuclei isolated from the cells which were pretreated with each of the four compounds, there was no significant difference in the amount among these compounds. The reason for the increase in the poly(ADP-ribosyl)ation in vitro by the in vivo treatment with thymidine is discussed."} {"id": "PMID:156180", "title": "Size and molecular parameters of adenosine triphosphatase from Escherichia coli.", "content": "The Mg2+- and Ca2+-stimulated ATPase (bacterial coupling factor) has been investigated in solution with different independent techniques. The molecular weight of the five-subunit enzyme was found to be 345,000 +/- 5,000 by means of light scattering, 350,000 by sedimentation equilibrium experiments, and 358,000 by means of small-angle x-ray scattering. The radius of gyration was found to be 41.9 A, the volume 7.39 x 10(5) A3, and the surface to volume ratio 5.5 x 10(-2) A-1 from small-angle x-ray scattering measurements of the enzyme in solution. The degree of hydration was found to be 0.62 ml of H2O/g of ATPase. The translational diffusion coefficient was determined to be 3.47 x 10(-7) cm2 s-1 by means of inelastic light scattering. The distribution of the scattered intensity near the origin appears to be bimodal, suggesting that the ATPase molecule is composed of spherical parts bound together by a flexible polypeptide chain. The largest dimension of the ATPase in solution is 120.0 A, determined from the pair distribution function.", "contents": "Size and molecular parameters of adenosine triphosphatase from Escherichia coli. The Mg2+- and Ca2+-stimulated ATPase (bacterial coupling factor) has been investigated in solution with different independent techniques. The molecular weight of the five-subunit enzyme was found to be 345,000 +/- 5,000 by means of light scattering, 350,000 by sedimentation equilibrium experiments, and 358,000 by means of small-angle x-ray scattering. The radius of gyration was found to be 41.9 A, the volume 7.39 x 10(5) A3, and the surface to volume ratio 5.5 x 10(-2) A-1 from small-angle x-ray scattering measurements of the enzyme in solution. The degree of hydration was found to be 0.62 ml of H2O/g of ATPase. The translational diffusion coefficient was determined to be 3.47 x 10(-7) cm2 s-1 by means of inelastic light scattering. The distribution of the scattered intensity near the origin appears to be bimodal, suggesting that the ATPase molecule is composed of spherical parts bound together by a flexible polypeptide chain. The largest dimension of the ATPase in solution is 120.0 A, determined from the pair distribution function."} {"id": "PMID:156182", "title": "Inactivation of phosphofructokinase by glucagon in rat hepatocytes.", "content": "Kinetic evidence of a time- and dose-dependent inactivation of phosphofructokinase by glucagon in isolated rat hepatocytes is reported. This inactivation, which persists after gel filtration of a cell-free extract on Sephadex G-25 and after 400-fold purification of the enzyme on agarose-ATP, is observed when the enzyme activity is measured at subsaturating concentrations of fructose 6-phosphate, while there is no change in Vmax. Phosphofructokinase inactivation by glucagon parallels the known inactivation of pyruvate kinase L and activation of glycogen phosphorylase alpha. Exogenous cyclic AMP mimics the effect of this hormone. Half-maximal effect for both phosphofructokinase and pyruvate kinase L is caused by a similar dose of glucagon (1 x 10(-10) M). The inactivation of phosphofructokinase by nonsaturating concentration of glucagon is reversed spontaneously within 40 min of incubation and this reversion is accelerated by insulin.", "contents": "Inactivation of phosphofructokinase by glucagon in rat hepatocytes. Kinetic evidence of a time- and dose-dependent inactivation of phosphofructokinase by glucagon in isolated rat hepatocytes is reported. This inactivation, which persists after gel filtration of a cell-free extract on Sephadex G-25 and after 400-fold purification of the enzyme on agarose-ATP, is observed when the enzyme activity is measured at subsaturating concentrations of fructose 6-phosphate, while there is no change in Vmax. Phosphofructokinase inactivation by glucagon parallels the known inactivation of pyruvate kinase L and activation of glycogen phosphorylase alpha. Exogenous cyclic AMP mimics the effect of this hormone. Half-maximal effect for both phosphofructokinase and pyruvate kinase L is caused by a similar dose of glucagon (1 x 10(-10) M). The inactivation of phosphofructokinase by nonsaturating concentration of glucagon is reversed spontaneously within 40 min of incubation and this reversion is accelerated by insulin."} {"id": "PMID:156184", "title": "The effect of ionomycin on calcium fluxes in sarcoplasmic reticulum vesicles and liposomes.", "content": "Ionomycin, a recently discovered calcium ionophore, inhibits the ATP-dependent active Ca2+ transport of rabbit sarcoplasmic reticulum vesicles at concentrations as low as 10(-8) to 10(-6) M. The effect is due to an increase in the Ca2+ permeability of the membrane which is also observed on liposomes. The inhibition of Ca2+ uptake is accompanied by an increase in the Ca2+-sensitive ATPase activity of sarcoplasmic reticulum vesicles.", "contents": "The effect of ionomycin on calcium fluxes in sarcoplasmic reticulum vesicles and liposomes. Ionomycin, a recently discovered calcium ionophore, inhibits the ATP-dependent active Ca2+ transport of rabbit sarcoplasmic reticulum vesicles at concentrations as low as 10(-8) to 10(-6) M. The effect is due to an increase in the Ca2+ permeability of the membrane which is also observed on liposomes. The inhibition of Ca2+ uptake is accompanied by an increase in the Ca2+-sensitive ATPase activity of sarcoplasmic reticulum vesicles."} {"id": "PMID:156187", "title": "Purification and reconstitution of the Ca2+-ATPase from plasma membrane of pig erythrocytes.", "content": "The Ca2+-ATPase from plasma membranes of pig erythrocytes was purified by mixed micelle gel chromatography (Wolf, H.U., Diekvoss, G., and Lichtner, R. (1977) Acta Biol. Med. Germ. 36, 847-858). The enzyme was activated at high concentrations of Tween 20 (10 mg/ml) or by appropriate mixtures of Triton X-100 and phospholipids. It was highly unstable in the absence of Ca2+ and activator protein. The Ca2+-ATPase was incorporated into liposomes by freeze-thaw sonication. After removal of non-ionic detergent by passage through a phenyl Sepharose 4B column, the reconstituted vesicles catalyzed a rapid ATP-dependent uptake of Ca2+. Modulator protein from brain substituted for the natural activator protein and stimulated Ca2+ uptake in reconstituted vesicles.", "contents": "Purification and reconstitution of the Ca2+-ATPase from plasma membrane of pig erythrocytes. The Ca2+-ATPase from plasma membranes of pig erythrocytes was purified by mixed micelle gel chromatography (Wolf, H.U., Diekvoss, G., and Lichtner, R. (1977) Acta Biol. Med. Germ. 36, 847-858). The enzyme was activated at high concentrations of Tween 20 (10 mg/ml) or by appropriate mixtures of Triton X-100 and phospholipids. It was highly unstable in the absence of Ca2+ and activator protein. The Ca2+-ATPase was incorporated into liposomes by freeze-thaw sonication. After removal of non-ionic detergent by passage through a phenyl Sepharose 4B column, the reconstituted vesicles catalyzed a rapid ATP-dependent uptake of Ca2+. Modulator protein from brain substituted for the natural activator protein and stimulated Ca2+ uptake in reconstituted vesicles."} {"id": "PMID:156193", "title": "Seventy-two hour infusions of LHRH in normal men: gonadotropin and testicular steroid responses.", "content": "Four normal male subjects received LHRH by continuous infusion for 72 hrs at 1.4 microgram/min. Mean basal LH was 7.7 +/- 1.0 mIU/ml, increased to a maximum of 120 +/- 22.7 mIU/ml, and then declined to levels between 28--34 mIU/ml for the last 30 hrs of infusion; FSH rose from 3.7 to 11.4 mIU/ml (p less than 0.05) at 16 hrs and then returned to baseline. Testosterone levels rose by 50% at 12 hrs, and remained elevated throughout with maximum values between 6.6 and 12 ng/ml. Estradiol-17beta levels were 26.2 +/- 4.7 pg/ml basally, rose to 104 +/- 8 pg/ml and while levels declined therafter, they were significantly above baseline throughout the 72 hrs. Plasma androstenedione and dehydroepiandrosterone levels also showed significant increases. By contrast, transient elevations in pregnenolone and 17-hydroxypregnenolone levels probably corresponded to the nomral morning rise in plasma levels of these steroids; 17-hydroxyprogesterone rose from 1.3 +/- 0.15 to 3.9 +/- 0.26 ng/ml at 12 hrs and remained elevated through the infusion. An increase in 17-hydroxyprogesterone:testosterone ratio was observed in all subjects. Thus, chronic LHRH infusion effected a persistent increase in endogenous LH with, in turn, prolonged stimulation of gonadal steroid secretion.", "contents": "Seventy-two hour infusions of LHRH in normal men: gonadotropin and testicular steroid responses. Four normal male subjects received LHRH by continuous infusion for 72 hrs at 1.4 microgram/min. Mean basal LH was 7.7 +/- 1.0 mIU/ml, increased to a maximum of 120 +/- 22.7 mIU/ml, and then declined to levels between 28--34 mIU/ml for the last 30 hrs of infusion; FSH rose from 3.7 to 11.4 mIU/ml (p less than 0.05) at 16 hrs and then returned to baseline. Testosterone levels rose by 50% at 12 hrs, and remained elevated throughout with maximum values between 6.6 and 12 ng/ml. Estradiol-17beta levels were 26.2 +/- 4.7 pg/ml basally, rose to 104 +/- 8 pg/ml and while levels declined therafter, they were significantly above baseline throughout the 72 hrs. Plasma androstenedione and dehydroepiandrosterone levels also showed significant increases. By contrast, transient elevations in pregnenolone and 17-hydroxypregnenolone levels probably corresponded to the nomral morning rise in plasma levels of these steroids; 17-hydroxyprogesterone rose from 1.3 +/- 0.15 to 3.9 +/- 0.26 ng/ml at 12 hrs and remained elevated through the infusion. An increase in 17-hydroxyprogesterone:testosterone ratio was observed in all subjects. Thus, chronic LHRH infusion effected a persistent increase in endogenous LH with, in turn, prolonged stimulation of gonadal steroid secretion."} {"id": "PMID:156194", "title": "Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol.", "content": "The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1).", "contents": "Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol. The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1)."} {"id": "PMID:156196", "title": "Congenital deficiency of alpha 2-plasmin inhibitor associated with severe hemorrhagic tendency.", "content": "alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis.", "contents": "Congenital deficiency of alpha 2-plasmin inhibitor associated with severe hemorrhagic tendency. alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis."} {"id": "PMID:156197", "title": "Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.", "content": "Studies were designed to investigate whether the suppressor cell systems that regulate the humoral and cell-mediated immune responses belong to the same subsets of T cells or different subsets. Mitogen-activated suppressor cells were simultaneously assayed for their ability to inhibit (a) pokeweed mitogen-induced generation of plasma cells, (b) blastogenic response of lymphocytes to allogeneic cells, and (c) generation of killer cells in the cell-mediated lymphocytotoxicity assay. We found that suppressor cells that inhibited the generation of plasma cells were activated by concanavalin A (Con A) and were both radiation and prednisone sensitive. Suppressors that inhibited the blastogenic response in lymphocytes to allogenic cells were also activated by Con A but differed in that they were both radiation and prednisone resistant. In contrast, suppressors that inhibited the generation of the killer cells were activated with phytohemagglutinin and not Con A. These suppressors were prednisone and radiation resistant. These observations cannot be explained by differences at the pro-suppressor or suppressor activator levels as both T cell subsets are radiosensitive. Alternatively, heterogeneity of suppressor cell systems may explain these differences.", "contents": "Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems. Studies were designed to investigate whether the suppressor cell systems that regulate the humoral and cell-mediated immune responses belong to the same subsets of T cells or different subsets. Mitogen-activated suppressor cells were simultaneously assayed for their ability to inhibit (a) pokeweed mitogen-induced generation of plasma cells, (b) blastogenic response of lymphocytes to allogeneic cells, and (c) generation of killer cells in the cell-mediated lymphocytotoxicity assay. We found that suppressor cells that inhibited the generation of plasma cells were activated by concanavalin A (Con A) and were both radiation and prednisone sensitive. Suppressors that inhibited the blastogenic response in lymphocytes to allogenic cells were also activated by Con A but differed in that they were both radiation and prednisone resistant. In contrast, suppressors that inhibited the generation of the killer cells were activated with phytohemagglutinin and not Con A. These suppressors were prednisone and radiation resistant. These observations cannot be explained by differences at the pro-suppressor or suppressor activator levels as both T cell subsets are radiosensitive. Alternatively, heterogeneity of suppressor cell systems may explain these differences."} {"id": "PMID:156198", "title": "Suppression of acute and chronic inflammation in tumor-bearing rats.", "content": "Both acute and chronic cellular inflammatory reactions were suppressed in rats bearing malignant tumors. Inhibition of the acute inflammatory reactions was demonstrated in immune complex-induced vasculitis and in the accumulation of leukocytes in subcutaneously implanted polyvinyl sponges. Suppression of chronic inflammatory reactions was demonstrated in delayed type hypersensitivity skin reactions. In spite of these suppressed reactions, dermal reactivity to vasopermeability mediators was not diminished. Neither serum complement levels nor numbers of circulating leukocytes were depressed in animals with tumors. Suppression of inflammatory reactions was paralleled by a leukotactic defect which involved both neutrophils and monocytes. This defect could be ascribed to an abnormality in the serum that rendered both cell types leukotactically defective.", "contents": "Suppression of acute and chronic inflammation in tumor-bearing rats. Both acute and chronic cellular inflammatory reactions were suppressed in rats bearing malignant tumors. Inhibition of the acute inflammatory reactions was demonstrated in immune complex-induced vasculitis and in the accumulation of leukocytes in subcutaneously implanted polyvinyl sponges. Suppression of chronic inflammatory reactions was demonstrated in delayed type hypersensitivity skin reactions. In spite of these suppressed reactions, dermal reactivity to vasopermeability mediators was not diminished. Neither serum complement levels nor numbers of circulating leukocytes were depressed in animals with tumors. Suppression of inflammatory reactions was paralleled by a leukotactic defect which involved both neutrophils and monocytes. This defect could be ascribed to an abnormality in the serum that rendered both cell types leukotactically defective."} {"id": "PMID:156201", "title": "Stress reactions of various judging groups to the child dental patient.", "content": "Dental personnel representing various levels of clinical experience and education in pedodontics were shown slides of potentially stressing situations within the field of pedodontics. Stress was identified through voice analysis by the Psychological Stress Evaluator (PSE-101). Clinical experience and education in pedodontics does not decrease either absolute or relative amounts of stress. Visual stimuli are capable of eliciting a stressful response. Trained raters can interpret voice prints with a satisfactory degree of inter-rater reliability. The PSE-101 is a valid indicator of stress.", "contents": "Stress reactions of various judging groups to the child dental patient. Dental personnel representing various levels of clinical experience and education in pedodontics were shown slides of potentially stressing situations within the field of pedodontics. Stress was identified through voice analysis by the Psychological Stress Evaluator (PSE-101). Clinical experience and education in pedodontics does not decrease either absolute or relative amounts of stress. Visual stimuli are capable of eliciting a stressful response. Trained raters can interpret voice prints with a satisfactory degree of inter-rater reliability. The PSE-101 is a valid indicator of stress."} {"id": "PMID:156202", "title": "Effect of indomethacin on Ca2+-stimulated adenosine triphosphatase in the microsomes of rat submandibular gland.", "content": "The effect of indomethacin, which is a nonsteroidal anti-inflammatory drug, on Ca2+-stimulated adenosine triphosphatase (Ca2+-ATPase) activity in the microsomes of rat submandibular gland was investigated. The effect of aspirin on Ca2+-ATPase activity was also studied.", "contents": "Effect of indomethacin on Ca2+-stimulated adenosine triphosphatase in the microsomes of rat submandibular gland. The effect of indomethacin, which is a nonsteroidal anti-inflammatory drug, on Ca2+-stimulated adenosine triphosphatase (Ca2+-ATPase) activity in the microsomes of rat submandibular gland was investigated. The effect of aspirin on Ca2+-ATPase activity was also studied."} {"id": "PMID:156207", "title": "Histochemical comparison of focal losses of RNase and ATPase activities in preneoplastic rat livers.", "content": "To better assess the significance of enzyme-deficient foci as putative premalignant lesions, parallel histochemical analyses of RNase and ATPase activities were carried out in serial sections of livers from rats fed 4-dimethylaminoazobenzene. The results showed that focal losses of RNase and canalicular ATPase activities occur simultaneously in congruent areas of liver parenchyma at early stages of carcinogenesis. Such foci presumably represent altered cells capable of progressing to neoplasia since the changes observed in this new cell population persist in developing tumors.", "contents": "Histochemical comparison of focal losses of RNase and ATPase activities in preneoplastic rat livers. To better assess the significance of enzyme-deficient foci as putative premalignant lesions, parallel histochemical analyses of RNase and ATPase activities were carried out in serial sections of livers from rats fed 4-dimethylaminoazobenzene. The results showed that focal losses of RNase and canalicular ATPase activities occur simultaneously in congruent areas of liver parenchyma at early stages of carcinogenesis. Such foci presumably represent altered cells capable of progressing to neoplasia since the changes observed in this new cell population persist in developing tumors."} {"id": "PMID:156208", "title": "Physiology of mixed leukocyte reaction suppressor factor. I. Role of cytoskeleton and protein synthesis in production and secretion.", "content": "The secretory physiology of the T cell-produced lymphokine, mixed leukocyte rection suppressor factor (MLR-TsF), was characterized with respect to its kinetics of secretion and its sensitivity ot a variety of metabolic blocking agents. It was found that spleen cells from alloantigen-immunized mice released active MLR-TsF after freeze-thaw lysis. Upon restimulation with the same priming alloantigen, MLR-TsF was secreted into culture supernatants, and the rate of secretion was determined to be nearly constant. Although colchicine and vinblastine, which bind to microtubules, are known inhibitors of lectin-induced proliferation, it was demonstrated that these drugs had no effect on the secretion of MLR-TsF. However, cytochalasin B, an inhibitor which also binds to some cytoskeletal and membrane-associated proteins, did inhibit the production of MLR-TsF. The above findings indicated that the activation-secretion mechanism of of MLR-TsF was much like that described for lymphotoxin and macrophage migration inhibition factors. The dissociation between DNA synthesis and lymphokine secretion was also demonstrated in the MLR-TsF system. DNA synthesis plays no role in the in vitro production of suppressor factor, as determined by resistance to treatment with mitomycin C and gamma-irradiation. However, new protein synthesis is required as indicated by the potent inhibitory effects of cycloheximide. Experiments utilizing timed addition and removal of cycloheximide defined a broad period of drug sensitivity, starting from the beginning of culture and lasting for 12 to 16 hr. In addition, experiments measuring the effect of cycloheximide on the MLR-TsF content of cell lysates demonstrated that the cell-associated lymphokine activity is lost when protein synthesis is interrupted. These experiments support the conclusion that MLR-TsF is synthesized de novo in culture. In addition, the secretory process itself may require protein synthesis.", "contents": "Physiology of mixed leukocyte reaction suppressor factor. I. Role of cytoskeleton and protein synthesis in production and secretion. The secretory physiology of the T cell-produced lymphokine, mixed leukocyte rection suppressor factor (MLR-TsF), was characterized with respect to its kinetics of secretion and its sensitivity ot a variety of metabolic blocking agents. It was found that spleen cells from alloantigen-immunized mice released active MLR-TsF after freeze-thaw lysis. Upon restimulation with the same priming alloantigen, MLR-TsF was secreted into culture supernatants, and the rate of secretion was determined to be nearly constant. Although colchicine and vinblastine, which bind to microtubules, are known inhibitors of lectin-induced proliferation, it was demonstrated that these drugs had no effect on the secretion of MLR-TsF. However, cytochalasin B, an inhibitor which also binds to some cytoskeletal and membrane-associated proteins, did inhibit the production of MLR-TsF. The above findings indicated that the activation-secretion mechanism of of MLR-TsF was much like that described for lymphotoxin and macrophage migration inhibition factors. The dissociation between DNA synthesis and lymphokine secretion was also demonstrated in the MLR-TsF system. DNA synthesis plays no role in the in vitro production of suppressor factor, as determined by resistance to treatment with mitomycin C and gamma-irradiation. However, new protein synthesis is required as indicated by the potent inhibitory effects of cycloheximide. Experiments utilizing timed addition and removal of cycloheximide defined a broad period of drug sensitivity, starting from the beginning of culture and lasting for 12 to 16 hr. In addition, experiments measuring the effect of cycloheximide on the MLR-TsF content of cell lysates demonstrated that the cell-associated lymphokine activity is lost when protein synthesis is interrupted. These experiments support the conclusion that MLR-TsF is synthesized de novo in culture. In addition, the secretory process itself may require protein synthesis."} {"id": "PMID:156209", "title": "Human macromolecular insoluble cold globulin (MICG). II. Immunologic definition of T cell and null cell MICG and the biologic effect of antiserum to MICG.", "content": "Thymus cell-derived macromolecular insoluble cold globulin (T-MICG) is a 225,000-dalton protein, selectively synthesized in human T cells. Null cell-derived macromolecular insoluble cold globulin (N-MICG) is a 185,000-dalton protein, synthesized in null cells, and antigenically distinct from T-MICG. Evidence to support these conclusions was provided by using isolated cell preparations that were radiolabeled, lysed in desoxycholate, and precipitated with monospecific antiserum to each component. These studies demonstrated that antiserum to T-MICG precipitated a 225,000 dalton protein from PBL and T cells, but not from B or null cells. Antiserum to N-MICG reacted with a 185,000 dalton protein present in PBL and null cells, but not with lysates from either T or B cells. The plasma membrane distribution of these proteins was shown by absorption of antiserum to T + N-MICG with either isolated T or null cells. Antibody-induced cytotoxicity and immunofluorescence confirmed the cell surface location of T and N-MICG. Divergent biologic effects of these antisera were also noted. Antiserum to T-MICG inhibited T cell rosette formation and the one-way mixed lymphocyte reaction, although anti-N-MICG antiserum had no such effect. The potential importance of these proteins is discussed.", "contents": "Human macromolecular insoluble cold globulin (MICG). II. Immunologic definition of T cell and null cell MICG and the biologic effect of antiserum to MICG. Thymus cell-derived macromolecular insoluble cold globulin (T-MICG) is a 225,000-dalton protein, selectively synthesized in human T cells. Null cell-derived macromolecular insoluble cold globulin (N-MICG) is a 185,000-dalton protein, synthesized in null cells, and antigenically distinct from T-MICG. Evidence to support these conclusions was provided by using isolated cell preparations that were radiolabeled, lysed in desoxycholate, and precipitated with monospecific antiserum to each component. These studies demonstrated that antiserum to T-MICG precipitated a 225,000 dalton protein from PBL and T cells, but not from B or null cells. Antiserum to N-MICG reacted with a 185,000 dalton protein present in PBL and null cells, but not with lysates from either T or B cells. The plasma membrane distribution of these proteins was shown by absorption of antiserum to T + N-MICG with either isolated T or null cells. Antibody-induced cytotoxicity and immunofluorescence confirmed the cell surface location of T and N-MICG. Divergent biologic effects of these antisera were also noted. Antiserum to T-MICG inhibited T cell rosette formation and the one-way mixed lymphocyte reaction, although anti-N-MICG antiserum had no such effect. The potential importance of these proteins is discussed."} {"id": "PMID:156210", "title": "Macromolecular insoluble cold globulin (MICG): a novel protein from mouse lymphocytes. III. Relationship to the mixed lymphocyte reaction and effect of anti-MICG antiserum in vivo.", "content": "In the present communication we have examined the relationship between the synthesis of macromolecular insoluble cold globulin (MICG) and the mixed lymphocyte reaction (MLR). In addition, we have studied in vivo the effect of antiserum to MICG on the antibody response to sheep red blood cells. The experiments indicate that MICG synthesis compared to either IgM or total protein is selectively stimulated in responder T cells exposed to allogeneic stimulator cells in the MLR. Furthermore, cytotoxicity studies utilizing anti-MICG antiserum demonstrated that T cells bearing MICG on their surface are an essential component of the responder cell population in the MLR. In vivo administration of antiserum to MICG significantly suppressed both the primary and secondary antibody response to sheep red blood cells. A possible mechanism for this suppression is discussed.", "contents": "Macromolecular insoluble cold globulin (MICG): a novel protein from mouse lymphocytes. III. Relationship to the mixed lymphocyte reaction and effect of anti-MICG antiserum in vivo. In the present communication we have examined the relationship between the synthesis of macromolecular insoluble cold globulin (MICG) and the mixed lymphocyte reaction (MLR). In addition, we have studied in vivo the effect of antiserum to MICG on the antibody response to sheep red blood cells. The experiments indicate that MICG synthesis compared to either IgM or total protein is selectively stimulated in responder T cells exposed to allogeneic stimulator cells in the MLR. Furthermore, cytotoxicity studies utilizing anti-MICG antiserum demonstrated that T cells bearing MICG on their surface are an essential component of the responder cell population in the MLR. In vivo administration of antiserum to MICG significantly suppressed both the primary and secondary antibody response to sheep red blood cells. A possible mechanism for this suppression is discussed."} {"id": "PMID:156212", "title": "Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose (2-DG): differential effect of 2-DG on effector cells isolated early or late after alloantigenic stimulation in vitro.", "content": "The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on the functional activity of various populations of cytolytic T lymphocytes (CTL) has been compared. Under aerobic conditions, CTL harvested at the peak of the response (day 4) in primary or secondary mixed leukocyte cultures (MLC) were much more readily inhibited by 2-DG that CTL obtained from MLC at later times (day 11 to 18) or from the peritoneal cavity of alloimmune mice. Quantitatively, 0.4 mM 2-DG was sufficpient to inhibit cytolysis by 50% in day 4 CTL populatons, whereas 25 mM had little or no effect on day 11 to 18 CTL. Evidence was obtained that inhibition of cytolysis by 2-DG under these conditions was accompanied by a parallel inhibition of effector:target cell binding. In contradistinction to these findings, the cytolytic activity of both day 4 and day 11 MLC cells was readily inhibited by 2-DG under conditions where cell respiration was blocked by sodium azide. Furthermore, uptake of radiolabeled 2-DG was observed under aerobic conditions in both day 4 and day 11 MLC cells. These results strongly suggest that inhibition of cytolysis by 2-DG under aerobic conditions is mediated via a direct effect on CTL which is independent of the consequences of energy depletion. An indirect method by which CTL may be inhibited by 2-DG is suggested.", "contents": "Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose (2-DG): differential effect of 2-DG on effector cells isolated early or late after alloantigenic stimulation in vitro. The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on the functional activity of various populations of cytolytic T lymphocytes (CTL) has been compared. Under aerobic conditions, CTL harvested at the peak of the response (day 4) in primary or secondary mixed leukocyte cultures (MLC) were much more readily inhibited by 2-DG that CTL obtained from MLC at later times (day 11 to 18) or from the peritoneal cavity of alloimmune mice. Quantitatively, 0.4 mM 2-DG was sufficpient to inhibit cytolysis by 50% in day 4 CTL populatons, whereas 25 mM had little or no effect on day 11 to 18 CTL. Evidence was obtained that inhibition of cytolysis by 2-DG under these conditions was accompanied by a parallel inhibition of effector:target cell binding. In contradistinction to these findings, the cytolytic activity of both day 4 and day 11 MLC cells was readily inhibited by 2-DG under conditions where cell respiration was blocked by sodium azide. Furthermore, uptake of radiolabeled 2-DG was observed under aerobic conditions in both day 4 and day 11 MLC cells. These results strongly suggest that inhibition of cytolysis by 2-DG under aerobic conditions is mediated via a direct effect on CTL which is independent of the consequences of energy depletion. An indirect method by which CTL may be inhibited by 2-DG is suggested."} {"id": "PMID:156214", "title": "Suppression of cell-mediated immune reactions by monosaccharides.", "content": "Various monosaccharides have been shown capable of inhibiting lymphokine activity in in vitro assay systems. In this study, we demonstrate that L-fucose can inhibit the ability of lymphokine-containing supernatants to induce skin reactions or cause reductions in the macrophage content of peritoneal exudates. Moreover, L-fucose can inhibit the cutaneous delayed hyoersensitivity reaction and the peritoneal macrophage disappearance reaction (MDR) induced by antigen in actively immunized guinea pigs. The effect of L-rhamnose, another sugar with in vitro inhibitory activity, was investigated in the MDR, and was also shown to be inhibitory. L-arabinose, which has no in vitro effects on lymphokines, had no suppressive effect on any of the in vivo systems studied. No monosaccharide inhibition of Arthus reactions or nonspecific inflammation could be found in these studies. The results demonstrate that monosaccharides capable of inhibiting lymphokine activity in vitro are effective in suppressing in vivo manifestations of cellular immunity.", "contents": "Suppression of cell-mediated immune reactions by monosaccharides. Various monosaccharides have been shown capable of inhibiting lymphokine activity in in vitro assay systems. In this study, we demonstrate that L-fucose can inhibit the ability of lymphokine-containing supernatants to induce skin reactions or cause reductions in the macrophage content of peritoneal exudates. Moreover, L-fucose can inhibit the cutaneous delayed hyoersensitivity reaction and the peritoneal macrophage disappearance reaction (MDR) induced by antigen in actively immunized guinea pigs. The effect of L-rhamnose, another sugar with in vitro inhibitory activity, was investigated in the MDR, and was also shown to be inhibitory. L-arabinose, which has no in vitro effects on lymphokines, had no suppressive effect on any of the in vivo systems studied. No monosaccharide inhibition of Arthus reactions or nonspecific inflammation could be found in these studies. The results demonstrate that monosaccharides capable of inhibiting lymphokine activity in vitro are effective in suppressing in vivo manifestations of cellular immunity."} {"id": "PMID:156215", "title": "Con A-inducible suppression of MLC: evidence for mediation by the TH2 + T cell subset in man.", "content": "Human peripheral lymphoid cells pretreated with Concanavalin A for 48 hr can markedly suppress the proliferative response of untreated autologous lymphoid cells in MLC. Isolation studies with Sephadex G-200 anti-F(ab')2 affinity chromatography, nylon adherence, and E rosetting indicate that the Con A-induced suppressor cell is a T cell. Further fractionation into TH2+ and TH2- cell subsets with an equine-anti TH2 serum show that both subsets can be activated by Con A to an equivalent degree. After activation only the TH2+ subset can suppress autologous responder cells in MLC. The TH2- subset, which comprises 80% of peripheral human T cells, although induced by Con A to proliferate, cannot itself suppress the MLC response. Nevertheless, the TH2- subset can be shown to modulate the generation of suppressor TH2+ cells at 24 hr but not at 48 hr. These studies support the notion that the Con A-induced suppressor cell is confined to a distinct T cell subset in man and that T-T interactions are important in the overall expression of the immune response.", "contents": "Con A-inducible suppression of MLC: evidence for mediation by the TH2 + T cell subset in man. Human peripheral lymphoid cells pretreated with Concanavalin A for 48 hr can markedly suppress the proliferative response of untreated autologous lymphoid cells in MLC. Isolation studies with Sephadex G-200 anti-F(ab')2 affinity chromatography, nylon adherence, and E rosetting indicate that the Con A-induced suppressor cell is a T cell. Further fractionation into TH2+ and TH2- cell subsets with an equine-anti TH2 serum show that both subsets can be activated by Con A to an equivalent degree. After activation only the TH2+ subset can suppress autologous responder cells in MLC. The TH2- subset, which comprises 80% of peripheral human T cells, although induced by Con A to proliferate, cannot itself suppress the MLC response. Nevertheless, the TH2- subset can be shown to modulate the generation of suppressor TH2+ cells at 24 hr but not at 48 hr. These studies support the notion that the Con A-induced suppressor cell is confined to a distinct T cell subset in man and that T-T interactions are important in the overall expression of the immune response."} {"id": "PMID:156216", "title": "Regulatory T cell subpopulations in pregnancy. I. Evidence for suppressive activity of the early phase of MLR.", "content": "Previous in vivo experiments have provided evidence of suppressive activity induced by multiple allogeneic pregnancies. The reactivity of maternal spleen cells toward paternal strain alloantigens was investigated by use of MLR microculture technique. A study of the kinetics of the MLR showed an early peak of reactivity (48-hr culture) followed by a decline leading to a decreased reactivity by 96 hr when spleen cells from allogeneically pregnant mice were compared to those of virgin or even isogeneically pregnant mice, suggesting the possible action of MLR regulatory cells. A strong suppression of a H-2k (CBA) anti-H-2a (A/J) or anti-H-2d (C57BL/Ks) MLR was observed when mitomycin-treated spleen cells from CBA mice multiparous by A/J or C57BL/Ks (but not CBA) males were added to the culture. This suppression was abolished by treating the regulatory cell population with anti-theta serum plus complement or replacing the 1% normal mouse serum in the medium by a proper antiidiotypic mouse serum.", "contents": "Regulatory T cell subpopulations in pregnancy. I. Evidence for suppressive activity of the early phase of MLR. Previous in vivo experiments have provided evidence of suppressive activity induced by multiple allogeneic pregnancies. The reactivity of maternal spleen cells toward paternal strain alloantigens was investigated by use of MLR microculture technique. A study of the kinetics of the MLR showed an early peak of reactivity (48-hr culture) followed by a decline leading to a decreased reactivity by 96 hr when spleen cells from allogeneically pregnant mice were compared to those of virgin or even isogeneically pregnant mice, suggesting the possible action of MLR regulatory cells. A strong suppression of a H-2k (CBA) anti-H-2a (A/J) or anti-H-2d (C57BL/Ks) MLR was observed when mitomycin-treated spleen cells from CBA mice multiparous by A/J or C57BL/Ks (but not CBA) males were added to the culture. This suppression was abolished by treating the regulatory cell population with anti-theta serum plus complement or replacing the 1% normal mouse serum in the medium by a proper antiidiotypic mouse serum."} {"id": "PMID:156217", "title": "Studies of the mechanisms for the induction of in vivo tumor immunity. IV. Enhancement of the in vitro generation of secondary cell-mediated cytotoxic response by normal peritoneal macrophages and their culture supernatants.", "content": "The effect of macrophages on the induction of the cell-mediated cytotoxicity against a leukemia in a syngeneic system was investigated. The addition of exogenous peritoneal cells from normal C57BL/6 MIce enhanced the in vitro secondary cell-mediated cytotoxic response of both spleen and lymph node cells as responding cells against syngeneic FBL-3 leukemia. Peritoneal phagocytic macrophages seemed to be responsible for the enhancement. No inhibitory effect was demonstrated by the addition of peritoneal macrophages at a concentration as high as 20%, whereas the primary cytotoxic allograft response was significantly suppressed. In the present studies, there was no absolute restriction of macrophage-T cell interaction by an H-2 barrier. Supernatants of peritoneal macrophage cultures also enhanced this cell-mediated cytotoxic response. There was no difference between the effects of syngeneic or allogeneic peritoneal macrophage culture supernatants.", "contents": "Studies of the mechanisms for the induction of in vivo tumor immunity. IV. Enhancement of the in vitro generation of secondary cell-mediated cytotoxic response by normal peritoneal macrophages and their culture supernatants. The effect of macrophages on the induction of the cell-mediated cytotoxicity against a leukemia in a syngeneic system was investigated. The addition of exogenous peritoneal cells from normal C57BL/6 MIce enhanced the in vitro secondary cell-mediated cytotoxic response of both spleen and lymph node cells as responding cells against syngeneic FBL-3 leukemia. Peritoneal phagocytic macrophages seemed to be responsible for the enhancement. No inhibitory effect was demonstrated by the addition of peritoneal macrophages at a concentration as high as 20%, whereas the primary cytotoxic allograft response was significantly suppressed. In the present studies, there was no absolute restriction of macrophage-T cell interaction by an H-2 barrier. Supernatants of peritoneal macrophage cultures also enhanced this cell-mediated cytotoxic response. There was no difference between the effects of syngeneic or allogeneic peritoneal macrophage culture supernatants."} {"id": "PMID:156220", "title": "DRw antisera react with activated T cells.", "content": "Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with \"Ia-like\" antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear.", "contents": "DRw antisera react with activated T cells. Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with \"Ia-like\" antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear."} {"id": "PMID:156221", "title": "Lung tumor-reactive cytotoxic lymphocytes generated in mixed lymphocyte reaction between C3HfeB/HeN (H-2kb) and C3H/HeN (H-2k) strain mice.", "content": "The tumor-associated transplantation antigen expressed by several transplacentally induced lung tumors of C3HfeB/HeN mice (H-2kb haplotype) has previously been shown to exist as a normal tissue alloantigen in mice of known H-2k and H-2a haplotypes. This antigen is not expressed in normal tissues of C3HfeB/HeN mice but is expressed in C3H/HeN mice, the strain from which the C3HfeB/HeN mice were originally derived. The present study indicates that spleen cells from C3HfeB/HeN and C3H/HeN mice respond reciprocally in the mixed lymphocyte reaction. Cytotoxic T lymphocytes specific for the tumor-associated alloantigen can be readily generated in mixed lymphocyte reactions in which spleen cells from C3HfeB/HeN mice are reacted with x-irradiated spleen cells from C3H/HeN or A strain mice. These cells are effective in suppressing the growth of the C3HfeB/HeN-derived lung tumor 85 in x-irradiated syngeneic recipients.", "contents": "Lung tumor-reactive cytotoxic lymphocytes generated in mixed lymphocyte reaction between C3HfeB/HeN (H-2kb) and C3H/HeN (H-2k) strain mice. The tumor-associated transplantation antigen expressed by several transplacentally induced lung tumors of C3HfeB/HeN mice (H-2kb haplotype) has previously been shown to exist as a normal tissue alloantigen in mice of known H-2k and H-2a haplotypes. This antigen is not expressed in normal tissues of C3HfeB/HeN mice but is expressed in C3H/HeN mice, the strain from which the C3HfeB/HeN mice were originally derived. The present study indicates that spleen cells from C3HfeB/HeN and C3H/HeN mice respond reciprocally in the mixed lymphocyte reaction. Cytotoxic T lymphocytes specific for the tumor-associated alloantigen can be readily generated in mixed lymphocyte reactions in which spleen cells from C3HfeB/HeN mice are reacted with x-irradiated spleen cells from C3H/HeN or A strain mice. These cells are effective in suppressing the growth of the C3HfeB/HeN-derived lung tumor 85 in x-irradiated syngeneic recipients."} {"id": "PMID:156226", "title": "Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells: demonstration of optimal conditions and target cell for factor activity.", "content": "A factor extracted from syngeneic thymic lymphoid cells (thymocytes) is shown to amplify the proliferative (MLC) response of syngeneic lymphoid cells to alloantigen in vitro. The optimal conditions for an effect of the thymus factor are quantitatively defined by kinetic and dose-response studies. Other variables that could potentially influence the activity of the thymus factor, such as the presence of 2-mercaptoethanol and the source of alloantigen, are identified. Factor activity can be recovered from semi-allogeneic thymocytes, as well as syngeneic thymocytes. The factor appears to predominantly effect the proliferative response of T cells localized in peripheral lymphoid organs. As such, this factor appears to be distinct from the variety of previously described factors derived from thymic reticuloepithelial elements that are thought to primarily induce the differentiation of T cell precursors found predominantly in bone marrow. Several possible mechanisms of action of this thymocyte-derived factor are considered.", "contents": "Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells: demonstration of optimal conditions and target cell for factor activity. A factor extracted from syngeneic thymic lymphoid cells (thymocytes) is shown to amplify the proliferative (MLC) response of syngeneic lymphoid cells to alloantigen in vitro. The optimal conditions for an effect of the thymus factor are quantitatively defined by kinetic and dose-response studies. Other variables that could potentially influence the activity of the thymus factor, such as the presence of 2-mercaptoethanol and the source of alloantigen, are identified. Factor activity can be recovered from semi-allogeneic thymocytes, as well as syngeneic thymocytes. The factor appears to predominantly effect the proliferative response of T cells localized in peripheral lymphoid organs. As such, this factor appears to be distinct from the variety of previously described factors derived from thymic reticuloepithelial elements that are thought to primarily induce the differentiation of T cell precursors found predominantly in bone marrow. Several possible mechanisms of action of this thymocyte-derived factor are considered."} {"id": "PMID:156227", "title": "Induction of autoreactive cells by the preculture of human peripheral blood mononuclear cells with the autologous fresh plasma.", "content": "An AMLR in which precultured cells proliferated in response to fresh non-T cells is described. In our system, the responder is human peripheral blood mononuclear cells precultured in the autologous fresh plasma for up to 16 days, and the stimulator is fresh autologous non-T cells. Results suggested that there were two subpopulations of autoreactive cells obtained from the preculture; the high and low density small lymphocytes, both having ERF activity. The autoreactivity of low density cells was augmented when either macrophages or N-ERF-cells were depleted from PBM and thereafter precultures wre performed. A survey of the functional characteristics of the responding cells showed that the responding cells had NK activity against Molt-4 cells but had no significant ADCC activity against target CRBC. Mechanisms for the induction of autoreactive cells by the preculture in the presence of autologous fresh plasma are discussed.", "contents": "Induction of autoreactive cells by the preculture of human peripheral blood mononuclear cells with the autologous fresh plasma. An AMLR in which precultured cells proliferated in response to fresh non-T cells is described. In our system, the responder is human peripheral blood mononuclear cells precultured in the autologous fresh plasma for up to 16 days, and the stimulator is fresh autologous non-T cells. Results suggested that there were two subpopulations of autoreactive cells obtained from the preculture; the high and low density small lymphocytes, both having ERF activity. The autoreactivity of low density cells was augmented when either macrophages or N-ERF-cells were depleted from PBM and thereafter precultures wre performed. A survey of the functional characteristics of the responding cells showed that the responding cells had NK activity against Molt-4 cells but had no significant ADCC activity against target CRBC. Mechanisms for the induction of autoreactive cells by the preculture in the presence of autologous fresh plasma are discussed."} {"id": "PMID:156228", "title": "The differentiation of cytotoxic T cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1 + cell dependent.", "content": "Within 15 hr of establishment of a murine mixed lymphocyte culture, a soluble mediator was produced that was capable of augmenting primary cytotoxic responses to alloantigen. The factor did not induce responsiveness in the absence of antigen, since the amplified response seen in its presence was specific for the stimulating alloantigen. The factor did not therefore appear to function by polyclonal activation of cytotoxic precursor cells. Production of the amplifying factor(s) was induced by unfractionated spleen cells, but not by cells subjected to UV irradiation or to sonication, making it likely that this deficiency is the basis of the well-documented failure of these stimulator cells to induce primary cytotoxic responses. The amplifying effects of the factor were distinctive from, but synergistic with, those of 2-mercaptoethanol. Production of the amplifying mediator did not require cell division but was dependent upon the presence of Lyt 1 + cells. On the other hand, Lyt 2 + cells were not needed for mediator production, but served as target cell population on which the factor exerted its action. These findings are compatible with the hypothesis that direct T-T cell collaboration can amplify the differentiation of cytotoxic cells.", "contents": "The differentiation of cytotoxic T cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1 + cell dependent. Within 15 hr of establishment of a murine mixed lymphocyte culture, a soluble mediator was produced that was capable of augmenting primary cytotoxic responses to alloantigen. The factor did not induce responsiveness in the absence of antigen, since the amplified response seen in its presence was specific for the stimulating alloantigen. The factor did not therefore appear to function by polyclonal activation of cytotoxic precursor cells. Production of the amplifying factor(s) was induced by unfractionated spleen cells, but not by cells subjected to UV irradiation or to sonication, making it likely that this deficiency is the basis of the well-documented failure of these stimulator cells to induce primary cytotoxic responses. The amplifying effects of the factor were distinctive from, but synergistic with, those of 2-mercaptoethanol. Production of the amplifying mediator did not require cell division but was dependent upon the presence of Lyt 1 + cells. On the other hand, Lyt 2 + cells were not needed for mediator production, but served as target cell population on which the factor exerted its action. These findings are compatible with the hypothesis that direct T-T cell collaboration can amplify the differentiation of cytotoxic cells."} {"id": "PMID:156229", "title": "Isolation and characterization of actin and myosin from B-lymphocytic guinea pig leukemia cells.", "content": "Actin and myosin have been isolated from a guinea pig B cell leukemia line, L2C. The m.w. and amino acid compositions of these proteins are similar to actin and myosin from other nonmuscle cell types. L2C actin polymerizes to form filaments and activates the ATPase activity of skeletal muscle myosin. Actin in crude lymphocyte extracts does not polymerize as well as predicted from the critical concentration of purified lymphocyte actin suggesting that other factors in lymphocyte extracts regulate actin polymerization. Lymphocyte myosin polymerizes to form synthetic filaments at low ionic strength. Lymphocyte myosin binds to actin, but its ATPase activity is not activated by actin. Possible mechanisms for regulation of the lymphocyte contractile apparatus and its importance in a number of lymphocyte functions are discussed.", "contents": "Isolation and characterization of actin and myosin from B-lymphocytic guinea pig leukemia cells. Actin and myosin have been isolated from a guinea pig B cell leukemia line, L2C. The m.w. and amino acid compositions of these proteins are similar to actin and myosin from other nonmuscle cell types. L2C actin polymerizes to form filaments and activates the ATPase activity of skeletal muscle myosin. Actin in crude lymphocyte extracts does not polymerize as well as predicted from the critical concentration of purified lymphocyte actin suggesting that other factors in lymphocyte extracts regulate actin polymerization. Lymphocyte myosin polymerizes to form synthetic filaments at low ionic strength. Lymphocyte myosin binds to actin, but its ATPase activity is not activated by actin. Possible mechanisms for regulation of the lymphocyte contractile apparatus and its importance in a number of lymphocyte functions are discussed."} {"id": "PMID:156230", "title": "Limiting dilution analysis of alloantigen-reactive T lymphocytes. III. Effect of priming on precursor frequencies.", "content": "The effect of specific priming with alloantigens on the frequency of cytolytic T lymphocyte precursors (CTL-P) has been investigated. Alloimmune lymphoid cells were obtained from the spleen of C57BL/6 (H-2b) mice primed with DBA/2 (H-2d) tumor cells or from 14-day unidirectional mixed leukocyte cultures (C57BL/6 anti-DBA/2). CTL-P frequencies directed against H-2d alloantigens were estimated by limiting dilution analysis in a sensitive micro MLC system. Under these conditions, an apparent increase of 3 to 4-fold in CTL-P frequency was observed in alloimmune (as compared with normal) C57BL/6 spleen cells. Evidence was obtained suggesting that this increase was specific for the priming alloantigens. A much greater increase in CTL-P frequency (25 to 100-fold) was observed after alloimmunization of C57BL/6 spleen cells in unidirectional MLC. Under the latter conditions, 5 to 20% of the surviving splenic MLC cells could be identified operationally as CTL-P. A similar enrichment in CTL-P frequency was obtained when lymph node, peripheral blood, or thymus cells were cultured for 14 days in MLC. These studies provide direct evidence that the pool of specific CTL-P can be expanded after alloimmunization. Furthermore, the very high frequencies observed after in vitro priming indicate that this system should be particularly useful for future studies of the progeny of individual CTL-P.", "contents": "Limiting dilution analysis of alloantigen-reactive T lymphocytes. III. Effect of priming on precursor frequencies. The effect of specific priming with alloantigens on the frequency of cytolytic T lymphocyte precursors (CTL-P) has been investigated. Alloimmune lymphoid cells were obtained from the spleen of C57BL/6 (H-2b) mice primed with DBA/2 (H-2d) tumor cells or from 14-day unidirectional mixed leukocyte cultures (C57BL/6 anti-DBA/2). CTL-P frequencies directed against H-2d alloantigens were estimated by limiting dilution analysis in a sensitive micro MLC system. Under these conditions, an apparent increase of 3 to 4-fold in CTL-P frequency was observed in alloimmune (as compared with normal) C57BL/6 spleen cells. Evidence was obtained suggesting that this increase was specific for the priming alloantigens. A much greater increase in CTL-P frequency (25 to 100-fold) was observed after alloimmunization of C57BL/6 spleen cells in unidirectional MLC. Under the latter conditions, 5 to 20% of the surviving splenic MLC cells could be identified operationally as CTL-P. A similar enrichment in CTL-P frequency was obtained when lymph node, peripheral blood, or thymus cells were cultured for 14 days in MLC. These studies provide direct evidence that the pool of specific CTL-P can be expanded after alloimmunization. Furthermore, the very high frequencies observed after in vitro priming indicate that this system should be particularly useful for future studies of the progeny of individual CTL-P."} {"id": "PMID:156231", "title": "Inhibition of the mixed lymphocyte reaction by fractionated niridazole urine dialysate.", "content": "Urine dialysate from rats treated orally with 25 mg/Kg 3H-labeled niridazole was fractionated by DEAE-Sepharose column chromatography and was found to contain three radioactive metabolites and no parent compound. When human niridazole urine dialysate (NUD) was fractionated under identical conditions, fractions corresponding to the three rat NUD metabolites were found to inhibit the human one-way MLR. No inhibition was obtained with fractionated control urine dialysate. It was concluded that nonimmunosuppressive niridazole is metabolized by rats and man to produce three active compounds with the ability to suppress the in vitro response to alloantigens.", "contents": "Inhibition of the mixed lymphocyte reaction by fractionated niridazole urine dialysate. Urine dialysate from rats treated orally with 25 mg/Kg 3H-labeled niridazole was fractionated by DEAE-Sepharose column chromatography and was found to contain three radioactive metabolites and no parent compound. When human niridazole urine dialysate (NUD) was fractionated under identical conditions, fractions corresponding to the three rat NUD metabolites were found to inhibit the human one-way MLR. No inhibition was obtained with fractionated control urine dialysate. It was concluded that nonimmunosuppressive niridazole is metabolized by rats and man to produce three active compounds with the ability to suppress the in vitro response to alloantigens."} {"id": "PMID:156234", "title": "Surface properties and in vitro functional capacities of human T lymphocyte subsets separated by linear density gradients.", "content": "Human lymphocytes derived from various central and peripheral sources were separated on linear density gradients (LDG). Cells from individual density fractions were tested in parallel for: the capacity to form nonimmune rosettes with neuraminidase-treated SRBC, the number of surface-associated HTLA, and in vitro proliferative responses to mitogenic lectins and alloantigens. Heterogeneous density distribution profiles were obtained for all sources of human T cells and revealed an organ specificity. The various T cell density classes obtained from identical organs as well as the identical density classes of different sources revealed to some extent differences in their surface marker patterns and/or their in vitro reactivities. On the basis of the combined techniques at least two major subsets among thymocytes were identified that differed in both surface properties and functional capacities. Density classes of T cells from all peripheral sources were distinguished from thymocytes by a homogeneous lowered HTLA expression. Whereas clear-cut differences in the in vitro functional capacity were observed between the two thymocyte subsets, less striking but still significant differences were found to exist among the various density classes of peripheral T cells.", "contents": "Surface properties and in vitro functional capacities of human T lymphocyte subsets separated by linear density gradients. Human lymphocytes derived from various central and peripheral sources were separated on linear density gradients (LDG). Cells from individual density fractions were tested in parallel for: the capacity to form nonimmune rosettes with neuraminidase-treated SRBC, the number of surface-associated HTLA, and in vitro proliferative responses to mitogenic lectins and alloantigens. Heterogeneous density distribution profiles were obtained for all sources of human T cells and revealed an organ specificity. The various T cell density classes obtained from identical organs as well as the identical density classes of different sources revealed to some extent differences in their surface marker patterns and/or their in vitro reactivities. On the basis of the combined techniques at least two major subsets among thymocytes were identified that differed in both surface properties and functional capacities. Density classes of T cells from all peripheral sources were distinguished from thymocytes by a homogeneous lowered HTLA expression. Whereas clear-cut differences in the in vitro functional capacity were observed between the two thymocyte subsets, less striking but still significant differences were found to exist among the various density classes of peripheral T cells."} {"id": "PMID:156235", "title": "Activation of suppressor T cells in human autologous mixed lymphocyte culture.", "content": "Co-culture of autologous T and mitomycin-C treated B cells results in increased DNA synthesis in the responding T cells. T cells thus activated in AMLC exerted suppressive effects on both the proliferative and cytotoxic responses of fresh unstimulated T cells to allogeneic cells in MLC. The suppressor cells generated are sensitive to treatment with mitomycin-C. AMLC-activated cells treated with mitomycin-C failed to suppress both cytotoxicity and proliferation in fresh primary MLC. It appears that the AMLC reaction reflects an immunologic homeostatic mechanism. Since this reaction is defective in patients with CLL and SLE and the homologous mouse syngeneic MLC is defective in NZB mice, the failure of this T-B interaction may be related to the pathogenesis of certain lymphoproliferative and autoimmune disorders.", "contents": "Activation of suppressor T cells in human autologous mixed lymphocyte culture. Co-culture of autologous T and mitomycin-C treated B cells results in increased DNA synthesis in the responding T cells. T cells thus activated in AMLC exerted suppressive effects on both the proliferative and cytotoxic responses of fresh unstimulated T cells to allogeneic cells in MLC. The suppressor cells generated are sensitive to treatment with mitomycin-C. AMLC-activated cells treated with mitomycin-C failed to suppress both cytotoxicity and proliferation in fresh primary MLC. It appears that the AMLC reaction reflects an immunologic homeostatic mechanism. Since this reaction is defective in patients with CLL and SLE and the homologous mouse syngeneic MLC is defective in NZB mice, the failure of this T-B interaction may be related to the pathogenesis of certain lymphoproliferative and autoimmune disorders."} {"id": "PMID:156241", "title": "The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes.", "content": "In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells.", "contents": "The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells."} {"id": "PMID:156242", "title": "Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors.", "content": "Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig.", "contents": "Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors. Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig."} {"id": "PMID:156243", "title": "Dermatoses of the scalp.", "content": "By judicious consideration of the clinical appearance, by direct examination with magnification, and by culture results, skin biopsy, and other laboratory results, the clinician is able to diagnose most pathological conditions of the scalp. The scalp participates in many systemic disorders and frequently is the chief site of involvement. Similarly, many generalized disorders limited to the skin exhibit their most typical manifestations in the scalp. Whenever a diagnosis eludes the investigator, more than likely he or she has not considered all of the etiological possibilities or has not pursued an adequate laboratory investigation. A few scalp diseases initially present nonspecific clinical pictures. By utilizing follow-up examinations at appropriate intervals, the diagnosis can eventually be made. Once a diagnosis is made, appropriate treatment will generally produce satisfactory improvement or cure. Nevertheless, a few generally rare conditions will defy the physician's most enlightened and aggressive therapy.", "contents": "Dermatoses of the scalp. By judicious consideration of the clinical appearance, by direct examination with magnification, and by culture results, skin biopsy, and other laboratory results, the clinician is able to diagnose most pathological conditions of the scalp. The scalp participates in many systemic disorders and frequently is the chief site of involvement. Similarly, many generalized disorders limited to the skin exhibit their most typical manifestations in the scalp. Whenever a diagnosis eludes the investigator, more than likely he or she has not considered all of the etiological possibilities or has not pursued an adequate laboratory investigation. A few scalp diseases initially present nonspecific clinical pictures. By utilizing follow-up examinations at appropriate intervals, the diagnosis can eventually be made. Once a diagnosis is made, appropriate treatment will generally produce satisfactory improvement or cure. Nevertheless, a few generally rare conditions will defy the physician's most enlightened and aggressive therapy."} {"id": "PMID:156240", "title": "Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa.", "content": "Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in Neurospora crassa. Genetic analysis of the mutants indicate that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the monofunctional alkylating agents, EI, EMS and ICR-177. It is suggested, therefore, that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.", "contents": "Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa. Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in Neurospora crassa. Genetic analysis of the mutants indicate that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the monofunctional alkylating agents, EI, EMS and ICR-177. It is suggested, therefore, that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents."} {"id": "PMID:156245", "title": "Reactions of 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) cadmium with tumor cells.", "content": "The cytotoxic properties of a bis(thiosemicarbazonato) cadmium complex are studied. Preincubation of Ehrlich cells with the complex prevents growth of the ascites tumor in mice. Although the complex inhibits tumor growth without undue initial toxocity, longer-term side effects limit the use of the compound. The complex inhibits incorporation of 3H-thymidine into DNA and the respiration of tumor cells. It is shown in the principal correlation that the complex is more inhibitory of the above biochemical processes than cadmium ion at equal cellular concentrations of the metal. In addition the cellular reactions of the cadmium, zinc, and copper bis(thiosemicarbazonato) complexes are compared. It is shown that subtle chemical differences in their chelate structures appear to be responsible for their marked differences in cellular reactivity.", "contents": "Reactions of 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) cadmium with tumor cells. The cytotoxic properties of a bis(thiosemicarbazonato) cadmium complex are studied. Preincubation of Ehrlich cells with the complex prevents growth of the ascites tumor in mice. Although the complex inhibits tumor growth without undue initial toxocity, longer-term side effects limit the use of the compound. The complex inhibits incorporation of 3H-thymidine into DNA and the respiration of tumor cells. It is shown in the principal correlation that the complex is more inhibitory of the above biochemical processes than cadmium ion at equal cellular concentrations of the metal. In addition the cellular reactions of the cadmium, zinc, and copper bis(thiosemicarbazonato) complexes are compared. It is shown that subtle chemical differences in their chelate structures appear to be responsible for their marked differences in cellular reactivity."} {"id": "PMID:156247", "title": "Pathogenesis of ano-rectal incontinence. A histometric study of the anal sphincter musculature.", "content": "Type 1 fibre predominance was found in the external anal sphincter, puborectalis and levator ani muscles of 17 control subjects, and of 16 patients with ano-rectal incontinence. In the external anal sphincter and puborectalis muscles of the control subjects the mean diameter of Type 2 fibres was slightly greater than that of Type 1 fibres, but in the levator ani muscles of control female subjects the mean diameter of Type 1 fibres was much greater than that of Type 2 fibres. In the patients with anorectal incontinence there was marked hypertrophy of fibres of both histochemical types. This was most marked in the puborectalis and external anal sphincter muscles. In 12 of the 16 incontinent patients there were histological and statistical features consistent with a neurogenic disorder. These histometric studies provide a quantitative basis for physiological and pathological studies of these muscles in incontinence and other anorectal disorders.", "contents": "Pathogenesis of ano-rectal incontinence. A histometric study of the anal sphincter musculature. Type 1 fibre predominance was found in the external anal sphincter, puborectalis and levator ani muscles of 17 control subjects, and of 16 patients with ano-rectal incontinence. In the external anal sphincter and puborectalis muscles of the control subjects the mean diameter of Type 2 fibres was slightly greater than that of Type 1 fibres, but in the levator ani muscles of control female subjects the mean diameter of Type 1 fibres was much greater than that of Type 2 fibres. In the patients with anorectal incontinence there was marked hypertrophy of fibres of both histochemical types. This was most marked in the puborectalis and external anal sphincter muscles. In 12 of the 16 incontinent patients there were histological and statistical features consistent with a neurogenic disorder. These histometric studies provide a quantitative basis for physiological and pathological studies of these muscles in incontinence and other anorectal disorders."} {"id": "PMID:156248", "title": "Familial carnitine deficiency. A fatal case and subclinical state in a sister.", "content": "A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked.", "contents": "Familial carnitine deficiency. A fatal case and subclinical state in a sister. A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked."} {"id": "PMID:156249", "title": "The anatomy of the so-called \"articular nerves\" and their relationship to facet denervation in the treatment of low-back pain.", "content": "Disections of the dorsal rami of L1--5 were performed in human cadavers, and the course of the dorsal rami, their branches, and the innervation of the zygapophyseal joints in the lumbar region were specifically studied. At the L-1 through L-4 levels, the dorsal rami divide into medial and lateral branches within the intertransverse ligaments. Each medial branch runs across the root of the adjacent superior articular process. At the caudal edge of the process, the branch turns medially beneath the mammillo-accessory ligament. Beneath the mammillo-accessory ligament, medial branches occur that innervate the adjacent zygapophyseal joint, and distal zygapophyseal branches arise at the laminar level to innervate the next lower joint. The L-5 dorsal ramus runs along a groove between the ala of the sacrum and its superior articular process. A the caudal edge of the articular process, the ramus divides into medial and lateral branches, and the medial branch supplies the L5--S1 articulation.", "contents": "The anatomy of the so-called \"articular nerves\" and their relationship to facet denervation in the treatment of low-back pain. Disections of the dorsal rami of L1--5 were performed in human cadavers, and the course of the dorsal rami, their branches, and the innervation of the zygapophyseal joints in the lumbar region were specifically studied. At the L-1 through L-4 levels, the dorsal rami divide into medial and lateral branches within the intertransverse ligaments. Each medial branch runs across the root of the adjacent superior articular process. At the caudal edge of the process, the branch turns medially beneath the mammillo-accessory ligament. Beneath the mammillo-accessory ligament, medial branches occur that innervate the adjacent zygapophyseal joint, and distal zygapophyseal branches arise at the laminar level to innervate the next lower joint. The L-5 dorsal ramus runs along a groove between the ala of the sacrum and its superior articular process. A the caudal edge of the articular process, the ramus divides into medial and lateral branches, and the medial branch supplies the L5--S1 articulation."} {"id": "PMID:156250", "title": "Susceptibility of kappa-casein components to various proteases.", "content": "In order to clarify the function of the carbohydrate moiety of bovine kappa-casein, kappa-casein components having different carbohydrate contents were prepared by DEAE-cellulose chromatography. Five adsorbed fractions so obtained had an identical peptide chain and contained carbohydrate moieties of increasing size in the order of components P-2, P-3, P-4, P-5 and P-6. The subsceptibility of kappa-casein components, having different carbohydrate contents, to various proteases was examined. kappa-Casein components were subjected to calf rennin [chymosin; EC 3.4.23.4], bovine trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], pronase [EC 3.4.24.4] and human plasmin [EC 3.4.21.7]. The component containing a larger carbohydrate moiety was less susceptible to hydrolysis than the component containing a smaller carbohydrate moiety. Rennin, trypsin, alpha-chymotrypsin and pronase hydrolyzed each component with a different reaction rate. On the contrary, human plasmin hydrolyzed component P-2, but did not hydrolyze component P-5. These results indicate that the carbohydrate moiety of kappa-casein components to various proteases.", "contents": "Susceptibility of kappa-casein components to various proteases. In order to clarify the function of the carbohydrate moiety of bovine kappa-casein, kappa-casein components having different carbohydrate contents were prepared by DEAE-cellulose chromatography. Five adsorbed fractions so obtained had an identical peptide chain and contained carbohydrate moieties of increasing size in the order of components P-2, P-3, P-4, P-5 and P-6. The subsceptibility of kappa-casein components, having different carbohydrate contents, to various proteases was examined. kappa-Casein components were subjected to calf rennin [chymosin; EC 3.4.23.4], bovine trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], pronase [EC 3.4.24.4] and human plasmin [EC 3.4.21.7]. The component containing a larger carbohydrate moiety was less susceptible to hydrolysis than the component containing a smaller carbohydrate moiety. Rennin, trypsin, alpha-chymotrypsin and pronase hydrolyzed each component with a different reaction rate. On the contrary, human plasmin hydrolyzed component P-2, but did not hydrolyze component P-5. These results indicate that the carbohydrate moiety of kappa-casein components to various proteases."} {"id": "PMID:156251", "title": "Gastroesophageal reflux among severely retarded children.", "content": "Of 136 institutionalized severely retarded children, 20 (15%) had recurrent vomiting. Of these 20, 15 had gastroesophageal reflux diagnosed by x-ray examination, acid reflux text, or both. Esophagitis was noted by endoscopy in ten of 14 patients with GER. Four patients were anemic and six had had one or more episodes of aspiration pneumonia in the 12 months prior to study. Reduced basal lower esophageal sphincter pressure was the most common manometric abnormality noted in the patients with GER. Responses of the LES to bethanechol and swallow were normal, as was the basal pressure of the upper esophageal sphincter. Abnormal propagation of esophageal peristalsis was seen in six patients, all of whom had moderate or severe esophagitis. When compared to the nonvomiting retarded patients, the GER patients had significantly lower mental age and higher incidence of scoliosis. Patients with GER who had basal LES pressure less than 10 mm Hg did not improve with medical management. Recurrent vomiting is a common and serious problem in severely retarded children, the organic cause of which can be demonstrated by the application of appropriate investigative techniques.", "contents": "Gastroesophageal reflux among severely retarded children. Of 136 institutionalized severely retarded children, 20 (15%) had recurrent vomiting. Of these 20, 15 had gastroesophageal reflux diagnosed by x-ray examination, acid reflux text, or both. Esophagitis was noted by endoscopy in ten of 14 patients with GER. Four patients were anemic and six had had one or more episodes of aspiration pneumonia in the 12 months prior to study. Reduced basal lower esophageal sphincter pressure was the most common manometric abnormality noted in the patients with GER. Responses of the LES to bethanechol and swallow were normal, as was the basal pressure of the upper esophageal sphincter. Abnormal propagation of esophageal peristalsis was seen in six patients, all of whom had moderate or severe esophagitis. When compared to the nonvomiting retarded patients, the GER patients had significantly lower mental age and higher incidence of scoliosis. Patients with GER who had basal LES pressure less than 10 mm Hg did not improve with medical management. Recurrent vomiting is a common and serious problem in severely retarded children, the organic cause of which can be demonstrated by the application of appropriate investigative techniques."} {"id": "PMID:156252", "title": "Urethral obstruction malformation complex: a cause of abdominal muscle deficiency and the \"prune belly\".", "content": "Abdominal muscle deficiency with a \"prune belly\" abdomen as been a major feature of the so-called prune belly syndrome, which has been regarded as a specific entity, although the etiology and developmental pathology are not understood. We present evidence that abdominal muscle deficiency is an etiologically nonspecific anatomic defect which is secondary to fetal abdominal distention of various causes. One of the more common causes is urethral obstruction with consequent early bladder distention, causing abdominal distention and other anomalies, a constellation of findings which we have termed the urethral obstruction malformation complex. This interpretation of the etiology of most cases of prune belly syndrome accounts for the male predominance, the observed variability in severity, and the lack of a defined mode of inheritance. Recurrence risk figures need to be redefined for each specific obstructing lesion of the urethra. The possibility of early prenatal diagnosis and management of fetuses with urethral obstruction needs further study.", "contents": "Urethral obstruction malformation complex: a cause of abdominal muscle deficiency and the \"prune belly\". Abdominal muscle deficiency with a \"prune belly\" abdomen as been a major feature of the so-called prune belly syndrome, which has been regarded as a specific entity, although the etiology and developmental pathology are not understood. We present evidence that abdominal muscle deficiency is an etiologically nonspecific anatomic defect which is secondary to fetal abdominal distention of various causes. One of the more common causes is urethral obstruction with consequent early bladder distention, causing abdominal distention and other anomalies, a constellation of findings which we have termed the urethral obstruction malformation complex. This interpretation of the etiology of most cases of prune belly syndrome accounts for the male predominance, the observed variability in severity, and the lack of a defined mode of inheritance. Recurrence risk figures need to be redefined for each specific obstructing lesion of the urethra. The possibility of early prenatal diagnosis and management of fetuses with urethral obstruction needs further study."} {"id": "PMID:156254", "title": "Fine structure of a racemose cysticercus from human brain.", "content": "The surface of a racemose cysticercus from the human brain was studied by scanning electron microscopy and the tegument of the cyst by transmission electron microscopy. The surface of the larva is covered by microvilli of uniform shape and size. The glycocalyx of the microvilli bears knotlike areas positive for acid mucopolysaccharides. Microvilli are interconnected by a fine, electron-dense network. The tegumental and subtegumental tissues vary in thickness from one region to the next, and the tissues below the vesicular layer are scattered irregularly, in a seemingly disordered manner.", "contents": "Fine structure of a racemose cysticercus from human brain. The surface of a racemose cysticercus from the human brain was studied by scanning electron microscopy and the tegument of the cyst by transmission electron microscopy. The surface of the larva is covered by microvilli of uniform shape and size. The glycocalyx of the microvilli bears knotlike areas positive for acid mucopolysaccharides. Microvilli are interconnected by a fine, electron-dense network. The tegumental and subtegumental tissues vary in thickness from one region to the next, and the tissues below the vesicular layer are scattered irregularly, in a seemingly disordered manner."} {"id": "PMID:156259", "title": "Surgical experience with expanded polytetrafluoroethylene (PTFE) as a replacement graft for traumatized vessels.", "content": "With the increased nationwide incidence of major vascular injuries, the need for interposition grafting has become quite common in major trauma centers. Despite extensive experience with such injuries, the choice of a substitute conduit remains controversial. Recent studies have demonstrated the potential of expanded polytetrafluoroethylene (PTFE) as a replacement graft for small arteries and veins. The surgical services at the Ben Taub General Hospital began to use PTFE grafts in traumatic vascular wounds approximately 2 years ago. Eight axillary arteries and 12 brachial arteries have had interposition grafting with PTFE prostheses. Eleven patients have required PTFE interposition grafts in repair of traumatized common, superficial, and profunda femoris arteries and common femoral veins; eight patients had reconstruction in the popliteal artery or vein. Three patients had renal artery revascularization procedures following blunt abdominal trauma, three patient had segmental replacement of the superior mesenteric artery following gunshot wounds, and one carotid artery, one iliac vein, and two axillary veins were grafted with PTFE. All patients with segmental repair of axillary, brachial, femoral, and popliteal vessels have maintained good distal pulses and viable extremities. No grafts have thrombosed, nor become infected, in spite of soft-tissue injury encountered at time or repair. In situations requiring interposition graft placement for reestablishment of distal flow in small arteries and veins, PTFE grafts appear to be an acceptable prosthesis.", "contents": "Surgical experience with expanded polytetrafluoroethylene (PTFE) as a replacement graft for traumatized vessels. With the increased nationwide incidence of major vascular injuries, the need for interposition grafting has become quite common in major trauma centers. Despite extensive experience with such injuries, the choice of a substitute conduit remains controversial. Recent studies have demonstrated the potential of expanded polytetrafluoroethylene (PTFE) as a replacement graft for small arteries and veins. The surgical services at the Ben Taub General Hospital began to use PTFE grafts in traumatic vascular wounds approximately 2 years ago. Eight axillary arteries and 12 brachial arteries have had interposition grafting with PTFE prostheses. Eleven patients have required PTFE interposition grafts in repair of traumatized common, superficial, and profunda femoris arteries and common femoral veins; eight patients had reconstruction in the popliteal artery or vein. Three patients had renal artery revascularization procedures following blunt abdominal trauma, three patient had segmental replacement of the superior mesenteric artery following gunshot wounds, and one carotid artery, one iliac vein, and two axillary veins were grafted with PTFE. All patients with segmental repair of axillary, brachial, femoral, and popliteal vessels have maintained good distal pulses and viable extremities. No grafts have thrombosed, nor become infected, in spite of soft-tissue injury encountered at time or repair. In situations requiring interposition graft placement for reestablishment of distal flow in small arteries and veins, PTFE grafts appear to be an acceptable prosthesis."} {"id": "PMID:156265", "title": "Quantitative analysis of dermatoglyphics. (2) Dermatoglyphic patterns.", "content": "Using medical students as controls, we devised a method of quantitative analysis of dermatoglyphic patterns. We calculated the frequency of appearance of each of the patterns and obtained the probability of occurrence of the dermatoglyphics of each of the controls. We showed usefulness of this method by presenting some examples of congenital anomalies where this has been put to use. Furthermore, patients with congential heart disease were compared with controls by this method.", "contents": "Quantitative analysis of dermatoglyphics. (2) Dermatoglyphic patterns. Using medical students as controls, we devised a method of quantitative analysis of dermatoglyphic patterns. We calculated the frequency of appearance of each of the patterns and obtained the probability of occurrence of the dermatoglyphics of each of the controls. We showed usefulness of this method by presenting some examples of congenital anomalies where this has been put to use. Furthermore, patients with congential heart disease were compared with controls by this method."} {"id": "PMID:156266", "title": "Exercise stress myocardial perfusion scintigraphy with thallium-201.", "content": "We performed exercise stress scintigraphy with thallium-201 in 88 patients including 31 patients of effort angina and nine patients of old myocardial infarction without angina. Sensitivity of exercise stress scintigraphy to detect effort angina was 77%, whereas sensitivity of exercise stress ECG was only 44.5%. The combination of stress scintigraphy with stress ECG enhanced sensitivity up to 87%. Exercise stress scintigraphy was useful particularly in cases with one vessel disease and those who failed to achieve sufficient exercise stress. Besides exercise stress scintigraphy did not show false positive response, differing from exercise stress ECG. Myocardial imaging is a method which shows the balance between myocardial perfusion demand and supply.", "contents": "Exercise stress myocardial perfusion scintigraphy with thallium-201. We performed exercise stress scintigraphy with thallium-201 in 88 patients including 31 patients of effort angina and nine patients of old myocardial infarction without angina. Sensitivity of exercise stress scintigraphy to detect effort angina was 77%, whereas sensitivity of exercise stress ECG was only 44.5%. The combination of stress scintigraphy with stress ECG enhanced sensitivity up to 87%. Exercise stress scintigraphy was useful particularly in cases with one vessel disease and those who failed to achieve sufficient exercise stress. Besides exercise stress scintigraphy did not show false positive response, differing from exercise stress ECG. Myocardial imaging is a method which shows the balance between myocardial perfusion demand and supply."} {"id": "PMID:156268", "title": "Importance of heart weight, weights of cardiac ventricles and left ventricle plus septum/right ventricle ratio in assessing cardiac hypertrophy.", "content": "The present communication deals with the observations made during the study of 140 hearts (138 from medico-legal postmortems and 2 from post-natal deaths). The formalin fixed heart was dissected to separate non-muscular portion (NMP), right ventricle (RV), and left ventricle with septum (LV + S). The weights of the different components of the adult heart were affected by sex and body built not by age or body length. In most of the hearts the total weight varied from 180 to 320 Gm, the weight of RV, from 40 to 80 Gm, and LV + S, from 100 to 180 Gm. NMP was neither affected by age nor by ventricular weight. The coefficient of correlation between the heart weight and NMP was 0.93. Heart weight in Gm could be represented as equaled to 38.89 + 4.09 NMP. LV + S/RV ratio ranged from 1.64-3.84 : 1 in males and 1.73--3.1 : 1 in females, averaged being 2.52 : 1 and 2.44 : 1 respectively. No correlation between the weights of RV and LV + S was found. An attempt has been made to lay down the criterion for normal heart and for ventricular hypertrophy. The importance of total heart weight, weights of ventricles and the ratio is assessment of cardiac hypertrophy is discussed.", "contents": "Importance of heart weight, weights of cardiac ventricles and left ventricle plus septum/right ventricle ratio in assessing cardiac hypertrophy. The present communication deals with the observations made during the study of 140 hearts (138 from medico-legal postmortems and 2 from post-natal deaths). The formalin fixed heart was dissected to separate non-muscular portion (NMP), right ventricle (RV), and left ventricle with septum (LV + S). The weights of the different components of the adult heart were affected by sex and body built not by age or body length. In most of the hearts the total weight varied from 180 to 320 Gm, the weight of RV, from 40 to 80 Gm, and LV + S, from 100 to 180 Gm. NMP was neither affected by age nor by ventricular weight. The coefficient of correlation between the heart weight and NMP was 0.93. Heart weight in Gm could be represented as equaled to 38.89 + 4.09 NMP. LV + S/RV ratio ranged from 1.64-3.84 : 1 in males and 1.73--3.1 : 1 in females, averaged being 2.52 : 1 and 2.44 : 1 respectively. No correlation between the weights of RV and LV + S was found. An attempt has been made to lay down the criterion for normal heart and for ventricular hypertrophy. The importance of total heart weight, weights of ventricles and the ratio is assessment of cardiac hypertrophy is discussed."} {"id": "PMID:156269", "title": "The estimation of heart weight from routine chest X-ray films.", "content": "A formula to estimate heart weight was derived using a theory of quantification which employed the measurements of cardiac silhouette taken from routine postero-anterior projection chest X-ray film. The films obtained in 73 necropsied cases of essential hypertension, renal hypertension, mitral and aortic valvular diseases, and 62 necropsied cases with other diseases were used for derivation of the formula. The measurements of the horizontal distances from the midsternal line to the intersecting point of the lower margin of each rib along the left cardiac border, and of the greatest distance along the right cardiac border were employed; body height, age and sex were also included. The heart weight estimated by this formula coincided with the heart weight measured at necropsy with a high correlation coefficient of 0.81. The correlation rate in 34 external samples was also significantly high, being 0.72. These results indicate the practical usefulness of this formula.", "contents": "The estimation of heart weight from routine chest X-ray films. A formula to estimate heart weight was derived using a theory of quantification which employed the measurements of cardiac silhouette taken from routine postero-anterior projection chest X-ray film. The films obtained in 73 necropsied cases of essential hypertension, renal hypertension, mitral and aortic valvular diseases, and 62 necropsied cases with other diseases were used for derivation of the formula. The measurements of the horizontal distances from the midsternal line to the intersecting point of the lower margin of each rib along the left cardiac border, and of the greatest distance along the right cardiac border were employed; body height, age and sex were also included. The heart weight estimated by this formula coincided with the heart weight measured at necropsy with a high correlation coefficient of 0.81. The correlation rate in 34 external samples was also significantly high, being 0.72. These results indicate the practical usefulness of this formula."} {"id": "PMID:156276", "title": "Homologous and heterologous connective tissue tube for vascular substitute.", "content": "A newly-developed vascular graft having many advantages over the fabric vascular prosthesis was evaluated as aortic and vena caval substitutes. Alcohol-preserved connective tissue tubes, obtained from dogs and calves, supported by polyester mesh were implanted into the thoracic aortae of 61 dogs and the superior vena cava of 24 dogs. In the case of the aortic experiment, all the tested animals were healthy and each graft was patent at the time of removal. In the case of the vena caval experiment, all the tested animals were healthy, but 10 of 24 grafts were occluded. Aneurysmal dilatation, immune response and regressive changes of newly formed neointima were not observed in any case. Moreover, no blood leakage through the graft wall was observed. Leakage at the line of anastomosis was very little. The great advantage of the graft was good endothelization of the neointima. Between the grafts obtained from dogs and calves, there was no difference in the process of their healing.", "contents": "Homologous and heterologous connective tissue tube for vascular substitute. A newly-developed vascular graft having many advantages over the fabric vascular prosthesis was evaluated as aortic and vena caval substitutes. Alcohol-preserved connective tissue tubes, obtained from dogs and calves, supported by polyester mesh were implanted into the thoracic aortae of 61 dogs and the superior vena cava of 24 dogs. In the case of the aortic experiment, all the tested animals were healthy and each graft was patent at the time of removal. In the case of the vena caval experiment, all the tested animals were healthy, but 10 of 24 grafts were occluded. Aneurysmal dilatation, immune response and regressive changes of newly formed neointima were not observed in any case. Moreover, no blood leakage through the graft wall was observed. Leakage at the line of anastomosis was very little. The great advantage of the graft was good endothelization of the neointima. Between the grafts obtained from dogs and calves, there was no difference in the process of their healing."} {"id": "PMID:156279", "title": "Human B-cell antigens in acute lymphocytic leukemia. Lack of correlation with other lymphocyte surface markers.", "content": "Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type.", "contents": "Human B-cell antigens in acute lymphocytic leukemia. Lack of correlation with other lymphocyte surface markers. Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type."} {"id": "PMID:156288", "title": "Suppressor cells in the pelvic lymph nodes regional to bladder cancer.", "content": "Regional lymph node cells from some patients with locally advanced bladder carcinoma were found to inhibit the reactivity of normal and autologous peripheral blood lymphocytes in mixed leukocyte culture. The data suggest that suppressor cells are generated in draining lymph nodes of these patients by a high concentration of tumor-derived products and may have suppressive influence on host immunologic defense mechanisms.", "contents": "Suppressor cells in the pelvic lymph nodes regional to bladder cancer. Regional lymph node cells from some patients with locally advanced bladder carcinoma were found to inhibit the reactivity of normal and autologous peripheral blood lymphocytes in mixed leukocyte culture. The data suggest that suppressor cells are generated in draining lymph nodes of these patients by a high concentration of tumor-derived products and may have suppressive influence on host immunologic defense mechanisms."} {"id": "PMID:156289", "title": "Pulmonary artery banding in infants with complete atrioventricular canal.", "content": "Management of symptomatic atrioventricular canal (AVC) in infancy may be difficult. Between July, 1969, and September, 1977, 31 infants with complete AVC presented in congestive heart failure (CHF) to the University of Minnesota Hospitals. Fifteen of these patients have responded to medical management and have been followed as outpatients. The other 16 patients remained in CHF. Six of them died of persistent heart failure within 4 months. The other 10 infants, aged 3 weeks to 1 year (mean 4 months), underwent pulmonary artery banding and seven survived operation. One of the survivors died with apparent pneumonia 1 month postoperatively. Each of the remaining six patients, who have been followed for 9 months to 9 years, had minimal mitral insufficiency and a large ventricular shunt. The three patients dying after banding had significant mitral insufficiency. We believe that pulmonary artery banding is an effective palliative procedure for infants with complete AVC and CHF who have large ventricular shunts and minimal mitral insufficiency.", "contents": "Pulmonary artery banding in infants with complete atrioventricular canal. Management of symptomatic atrioventricular canal (AVC) in infancy may be difficult. Between July, 1969, and September, 1977, 31 infants with complete AVC presented in congestive heart failure (CHF) to the University of Minnesota Hospitals. Fifteen of these patients have responded to medical management and have been followed as outpatients. The other 16 patients remained in CHF. Six of them died of persistent heart failure within 4 months. The other 10 infants, aged 3 weeks to 1 year (mean 4 months), underwent pulmonary artery banding and seven survived operation. One of the survivors died with apparent pneumonia 1 month postoperatively. Each of the remaining six patients, who have been followed for 9 months to 9 years, had minimal mitral insufficiency and a large ventricular shunt. The three patients dying after banding had significant mitral insufficiency. We believe that pulmonary artery banding is an effective palliative procedure for infants with complete AVC and CHF who have large ventricular shunts and minimal mitral insufficiency."} {"id": "PMID:156291", "title": "New approach to protein-losing gastroenteropathy.", "content": "Fibrinolytic activity in the biopsied gastrointestinal mucosa was investigated in patients with protein-losing gastroenteropathy, and the increased activity was observed in patients associated with erosive gastritis, Menetrier's disease, atrophic gastritis, or Crohn's disease. However, patients with intestinal lymphangiectasia showed normal mucosal fibrinolysis. Antifibrinolytic therapy with tranexamic acid revealed significant therapeutic effect in the group with increased mucosal fibrinolysis. It is concluded that tranexamic acid appeared to be successful in blocking the vicious circle of \"membrane disorder\",\"increased tissue fibrinolysis\", \"increased vascular permeability\", and \"hypoproteinemia\" in protein-losing gastroenteropathy.", "contents": "New approach to protein-losing gastroenteropathy. Fibrinolytic activity in the biopsied gastrointestinal mucosa was investigated in patients with protein-losing gastroenteropathy, and the increased activity was observed in patients associated with erosive gastritis, Menetrier's disease, atrophic gastritis, or Crohn's disease. However, patients with intestinal lymphangiectasia showed normal mucosal fibrinolysis. Antifibrinolytic therapy with tranexamic acid revealed significant therapeutic effect in the group with increased mucosal fibrinolysis. It is concluded that tranexamic acid appeared to be successful in blocking the vicious circle of \"membrane disorder\",\"increased tissue fibrinolysis\", \"increased vascular permeability\", and \"hypoproteinemia\" in protein-losing gastroenteropathy."} {"id": "PMID:156292", "title": "Exteroceptive, proprioceptive, and sympathetic activity recorded with microelectrodes from human peripheral nerves.", "content": "With tungsten microelectrodes percutaneously inserted into human peripheral nerve fascicles, in vivo recordings of single-unit action potentials can be obtained from different types of myelinated and unmyelinated nerve fibers. This technique of microneurography has provided a great deal of information about (1) the sensory innervation of the human skin, with its mechanoreceptive, thermoreceptive, and nociceptive functions, (2) the proprioceptive innervation of human skeletal muscles, special attention being devoted to the motor control functions of the muscle spindles and the fusimotor system, and (3) the sympathetic innervation of autonomic effector organs in skin and muscle, with its significance for, for example, regulation of temperature and blood pressure. The technique has its main application not as a routine procedure in clinical diagnostic work but as a research tool in basic physiologic and pathophysiologic studies.", "contents": "Exteroceptive, proprioceptive, and sympathetic activity recorded with microelectrodes from human peripheral nerves. With tungsten microelectrodes percutaneously inserted into human peripheral nerve fascicles, in vivo recordings of single-unit action potentials can be obtained from different types of myelinated and unmyelinated nerve fibers. This technique of microneurography has provided a great deal of information about (1) the sensory innervation of the human skin, with its mechanoreceptive, thermoreceptive, and nociceptive functions, (2) the proprioceptive innervation of human skeletal muscles, special attention being devoted to the motor control functions of the muscle spindles and the fusimotor system, and (3) the sympathetic innervation of autonomic effector organs in skin and muscle, with its significance for, for example, regulation of temperature and blood pressure. The technique has its main application not as a routine procedure in clinical diagnostic work but as a research tool in basic physiologic and pathophysiologic studies."} {"id": "PMID:156293", "title": "HLA.", "content": "HLA typing in 1979 is more complex and more complete than in former years. The distribution of antigens in the HLA system and various methods of identifying them and of determining their structure and function are described. The usefulness of HLA typing in organ transplantation and paternity testing has been well established, and its place in blood component therapy is to some degree still conjectural. Detection of HLA antigens associated either positively or negatively with specific disease states has great importance for several reasons. From an academic point of view, these association may help to define pathogenetic mechanisms, and from a practical viewpoint, there is now good reason to believe that HLA typing may shortly be useful as a diagnostic and predictive tool. Further elucidation of the role of the HLA molecules in the immune response gives hope for better understanding of the immune and autoimmune disorders, which is surely the first step in defining rationally based therapeutic regimens.", "contents": "HLA. HLA typing in 1979 is more complex and more complete than in former years. The distribution of antigens in the HLA system and various methods of identifying them and of determining their structure and function are described. The usefulness of HLA typing in organ transplantation and paternity testing has been well established, and its place in blood component therapy is to some degree still conjectural. Detection of HLA antigens associated either positively or negatively with specific disease states has great importance for several reasons. From an academic point of view, these association may help to define pathogenetic mechanisms, and from a practical viewpoint, there is now good reason to believe that HLA typing may shortly be useful as a diagnostic and predictive tool. Further elucidation of the role of the HLA molecules in the immune response gives hope for better understanding of the immune and autoimmune disorders, which is surely the first step in defining rationally based therapeutic regimens."} {"id": "PMID:156294", "title": "Otitis media and the immotile cilia syndrome.", "content": "The immotile cilia syndrome appears to be a congenital defect in the ultrastructure of cilia that renders them incapable of movement. Respiratory tract cilia and sperm are predominantly affected. Bronchiectasis, sinusitis and male sterility are the main clinical findings. Situs inversus may be found. To these findings can be added otitis media. The defect appears to be a complete or partial absence of dynein arms which are believed to be essential for generating movement of cilia or sperm tails. Six patients suspected of having immotile cilia were compared to six patients in a control group. In affected patients, no cilia movement in the middle ear or nasopharynx was observed using the operating microscope. Electron microscopy of cilia from the mucosa of the middle ear and nasopharynx appeared to confirm the ultrastructural defect in two of six patients suspected of having the syndrome.", "contents": "Otitis media and the immotile cilia syndrome. The immotile cilia syndrome appears to be a congenital defect in the ultrastructure of cilia that renders them incapable of movement. Respiratory tract cilia and sperm are predominantly affected. Bronchiectasis, sinusitis and male sterility are the main clinical findings. Situs inversus may be found. To these findings can be added otitis media. The defect appears to be a complete or partial absence of dynein arms which are believed to be essential for generating movement of cilia or sperm tails. Six patients suspected of having immotile cilia were compared to six patients in a control group. In affected patients, no cilia movement in the middle ear or nasopharynx was observed using the operating microscope. Electron microscopy of cilia from the mucosa of the middle ear and nasopharynx appeared to confirm the ultrastructural defect in two of six patients suspected of having the syndrome."} {"id": "PMID:156300", "title": "Metabolism of lipids in experimental hypertrophic hearts of rabbits.", "content": "Cardiac hypertrophy was induced in rabbits by subcutaneous injection of thyroxine or isoprenaline or by surgically constricting the abdominal aorta. Alterations in lipid metabolism were observed in these hypertrophic hearts. Thyroxine or isoprenaline treatment increased the fatty acids in the serum and stimulated a marked increase in total lipids, triglycerides, and fatty acids in the hypertrophied myocardium. Coarctation of the aorta, in contrast, induced a significant increase in these lipids without significantly affecting serum free fatty acids. Histochemical and morphological studies confirmed an increase in neutral lipids. It is suggested that the observed increase in fatty acids in the heart following thyroxine or isoprenaline treatment is related to the increase in serum free fatty acids, which is followed by an increase in the removal of serum fatty acids by the heart. However, the amount of serum fatty acids that is removed exceeds the amount that is oxidized, which leads to an increase in lipid stores. The increase in lipid stores in the heart following coarctation of the aorta probably corresponds to the decrease in myocardial concentrations of carnitine. Serum lipid levels following coarctation were not significantly different from those of controls.", "contents": "Metabolism of lipids in experimental hypertrophic hearts of rabbits. Cardiac hypertrophy was induced in rabbits by subcutaneous injection of thyroxine or isoprenaline or by surgically constricting the abdominal aorta. Alterations in lipid metabolism were observed in these hypertrophic hearts. Thyroxine or isoprenaline treatment increased the fatty acids in the serum and stimulated a marked increase in total lipids, triglycerides, and fatty acids in the hypertrophied myocardium. Coarctation of the aorta, in contrast, induced a significant increase in these lipids without significantly affecting serum free fatty acids. Histochemical and morphological studies confirmed an increase in neutral lipids. It is suggested that the observed increase in fatty acids in the heart following thyroxine or isoprenaline treatment is related to the increase in serum free fatty acids, which is followed by an increase in the removal of serum fatty acids by the heart. However, the amount of serum fatty acids that is removed exceeds the amount that is oxidized, which leads to an increase in lipid stores. The increase in lipid stores in the heart following coarctation of the aorta probably corresponds to the decrease in myocardial concentrations of carnitine. Serum lipid levels following coarctation were not significantly different from those of controls."} {"id": "PMID:156301", "title": "Constitutive expression in Escherichia coli of the Neurospora crassa structural gene encoding the inducible enzyme catabolic dehydroquinase.", "content": "In Neurospora crassa the qa-2 gene, which encodes catabolic dehydroquinase, is under positive control exerted by the inducer quinic acid and an activator protein encoded in the closely linked qa-1 gene. In order to determine if this regulatory mechanism is maintained when the qa-2 gene is cloned on a recombinant plasmid and expressed in Escherichia coli, molecular cloning experiments have been performed using DNA isolated from a qa-1+ (inducible), a qa-1C (constitutive) and two qa-1 (non-inducible) strains of N. crassa. The results demonstrate that the level of expression of the qa-2 gene in E. coli is completely independent of the mutational state of the qa-1 gene. Moreover, the level of expression of the cloned qa-2 gene was unaffected by either an intracellularly produced inducer of catabolic dehydroquinase or by the general procaryotic positive effector, the CAP factor. The weight of evidence thus supports the conclusion that transcription of the N. crassa qa-2 gene in E. coli does not require the qa-1 activator protein and thus is not controlled by the same mecahnism which functions in N. crassa.", "contents": "Constitutive expression in Escherichia coli of the Neurospora crassa structural gene encoding the inducible enzyme catabolic dehydroquinase. In Neurospora crassa the qa-2 gene, which encodes catabolic dehydroquinase, is under positive control exerted by the inducer quinic acid and an activator protein encoded in the closely linked qa-1 gene. In order to determine if this regulatory mechanism is maintained when the qa-2 gene is cloned on a recombinant plasmid and expressed in Escherichia coli, molecular cloning experiments have been performed using DNA isolated from a qa-1+ (inducible), a qa-1C (constitutive) and two qa-1 (non-inducible) strains of N. crassa. The results demonstrate that the level of expression of the qa-2 gene in E. coli is completely independent of the mutational state of the qa-1 gene. Moreover, the level of expression of the cloned qa-2 gene was unaffected by either an intracellularly produced inducer of catabolic dehydroquinase or by the general procaryotic positive effector, the CAP factor. The weight of evidence thus supports the conclusion that transcription of the N. crassa qa-2 gene in E. coli does not require the qa-1 activator protein and thus is not controlled by the same mecahnism which functions in N. crassa."} {"id": "PMID:156304", "title": "\"Prune Belly\" syndrome.", "content": "A large sonolucent mass was first revealed by the ultrasonic echography examination of a fetus at 18 1/2 weeks' gestation, but was no longer present at 28 1/2 weeks' gestation. The fetus was subsequently born with the \"prune belly\" syndrome. The case is described, and the possible causes, and possibilities of prevention, of \"prune belly\" are discussed.", "contents": "\"Prune Belly\" syndrome. A large sonolucent mass was first revealed by the ultrasonic echography examination of a fetus at 18 1/2 weeks' gestation, but was no longer present at 28 1/2 weeks' gestation. The fetus was subsequently born with the \"prune belly\" syndrome. The case is described, and the possible causes, and possibilities of prevention, of \"prune belly\" are discussed."} {"id": "PMID:156307", "title": "Structure and control of phosphofructokinase from Bacillus stearothermophilus.", "content": "The allosteric enzyme phosphofructokinase binds its substrate fructose-6-phosphate between two subunits of the tetramer, and allosteric effectors between another pair of subunits. The effector binding site accommodates both the activator and the inhibitor. The substrate cooperativity and allosteric control are mediated by these ligand bridges between subunits.", "contents": "Structure and control of phosphofructokinase from Bacillus stearothermophilus. The allosteric enzyme phosphofructokinase binds its substrate fructose-6-phosphate between two subunits of the tetramer, and allosteric effectors between another pair of subunits. The effector binding site accommodates both the activator and the inhibitor. The substrate cooperativity and allosteric control are mediated by these ligand bridges between subunits."} {"id": "PMID:156311", "title": "Development and mechanism of barbiturate tolerance in glial cell cultures.", "content": "The effects of exposure of glial cells in primary culture and in continuous line (clone NN) to pentobarbital over various periods of time on cellular respiration and activities of enzymes involved in carbohydrate metabolism were studied. The results obtained in glial cells in primary culture were qualitatively identical to those obtained in glial cells in clonal line (NN). Both types of glial cells were shown to develop biochemical tolerance to pentobarbital as defined by an attenuated response to the depressant effects of a challenging dose of pentobarbital on cellular respiration in barbiturate-cultivated cells compared to those grown in drug-free medium. The biochemical tolerance was evident in the presence of glucose and succinate but not malate as substrate. This tolerance to pentobarbital was accompanied by increased activities of hexokinase, glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and glutamate dehydrogenase and by a marked increase in the number of glial cell mitochondria as observed in electron micrographs. The results are interpreted to indicate a compensation of glial cells to the continuous presence of PB by an accelerated glucose uptake and metabolism, an accelerated metabolism of succinate, and an increased mitochondrial activity.", "contents": "Development and mechanism of barbiturate tolerance in glial cell cultures. The effects of exposure of glial cells in primary culture and in continuous line (clone NN) to pentobarbital over various periods of time on cellular respiration and activities of enzymes involved in carbohydrate metabolism were studied. The results obtained in glial cells in primary culture were qualitatively identical to those obtained in glial cells in clonal line (NN). Both types of glial cells were shown to develop biochemical tolerance to pentobarbital as defined by an attenuated response to the depressant effects of a challenging dose of pentobarbital on cellular respiration in barbiturate-cultivated cells compared to those grown in drug-free medium. The biochemical tolerance was evident in the presence of glucose and succinate but not malate as substrate. This tolerance to pentobarbital was accompanied by increased activities of hexokinase, glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and glutamate dehydrogenase and by a marked increase in the number of glial cell mitochondria as observed in electron micrographs. The results are interpreted to indicate a compensation of glial cells to the continuous presence of PB by an accelerated glucose uptake and metabolism, an accelerated metabolism of succinate, and an increased mitochondrial activity."} {"id": "PMID:156313", "title": "Isoniazid therapy of Huntington disease.", "content": "We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five greater than normally used in tuberculosis. Because INH inhibits the enzyme gamma-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed signifciant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease.", "contents": "Isoniazid therapy of Huntington disease. We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five greater than normally used in tuberculosis. Because INH inhibits the enzyme gamma-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed signifciant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease."} {"id": "PMID:156317", "title": "[Histoenzymatic changes and dosimetric studies of some organs and areas, using diagnostic radioisotopes. Critical review of a 10-year experiment].", "content": "Ten years experience of dosimetry and study of the histochemical changes brought on by internal irradiation are reviewed. The research is broken down into three stages: 1) identification of enzymatic damage in small laboratory animals; 2) study of the dose really absorbed at various points of critical organs of large animals, 3) the collection of histoenzymatic data resulting from research on large animals treated internally with isotopes commonly used in diagnosis.", "contents": "[Histoenzymatic changes and dosimetric studies of some organs and areas, using diagnostic radioisotopes. Critical review of a 10-year experiment]. Ten years experience of dosimetry and study of the histochemical changes brought on by internal irradiation are reviewed. The research is broken down into three stages: 1) identification of enzymatic damage in small laboratory animals; 2) study of the dose really absorbed at various points of critical organs of large animals, 3) the collection of histoenzymatic data resulting from research on large animals treated internally with isotopes commonly used in diagnosis."} {"id": "PMID:156318", "title": "The passive hamstring stretch test: clinical evaluation.", "content": "The passive hamstring stretch test is described. Using a modified goniometer it is shown that independent measurements taken by trained examiners approximate very closely to each other. This establishes the test as a valid objective measurement. The possible value of this test as a research tool in low back pain problems is discussed.", "contents": "The passive hamstring stretch test: clinical evaluation. The passive hamstring stretch test is described. Using a modified goniometer it is shown that independent measurements taken by trained examiners approximate very closely to each other. This establishes the test as a valid objective measurement. The possible value of this test as a research tool in low back pain problems is discussed."} {"id": "PMID:156320", "title": "Silicone band sterilization with radiographic and laparoscopic evaluation.", "content": "Laparoscopic tubal sterilization, using a Silastic band to occlude the tubal lumen, was performed on 224 patients. The incidence of complications was low and only 2 pregnancies occurred. Further evaluation by hysterosalpingography on 97 patients revealed 2 distinct images. The site of tubal occlusion was seen on laparoscopy performed on 7 patients. The radiographic and laparoscopic findings are discussed.", "contents": "Silicone band sterilization with radiographic and laparoscopic evaluation. Laparoscopic tubal sterilization, using a Silastic band to occlude the tubal lumen, was performed on 224 patients. The incidence of complications was low and only 2 pregnancies occurred. Further evaluation by hysterosalpingography on 97 patients revealed 2 distinct images. The site of tubal occlusion was seen on laparoscopy performed on 7 patients. The radiographic and laparoscopic findings are discussed."} {"id": "PMID:156321", "title": "Placental steroid synthesis from DHEAS during dexamethasone therapy.", "content": "Maternal glucocorticoid treatment affects estrogen synthesis by decreasing estrogen precursors. Whether glucocorticoid has any effect on the placental conversion of estrogen precursors to estrogen is not known. A study was therefore undertaken to investigate the effect of 100 mg of intravenously administered dehydroepiandrosterone sulfate (DHEAS) on estradiol (E2), estriol (E3), and testosterone (T) serum levels. The test was conducted for 5 hours in 10 women treated with intramuscular dexamethasone and in 8 controls during the last trimester of pregnancy. The initial E2 and E3 serum concentrations were lower in women treated with dexamethasone than in controls, while T serum levels did not display any difference. Following the injection of DHEAS there was a significant increase in E2, with maximal levels reached between 1 and 3 hours after injection in both groups. Maximal levels of E2 were equal for both groups. There was no change in E3 levels after DHEAS administration in the nontreated group, while the increase in the dexamethasone group was significant. A significant rise in T, with maximal levels reached at 1 hour after infusion, was similar in both groups. It is concluded that maternal dexamethasone does not inhibit the conversion of DHEAS either to E2 in the placenta or to E3 and T.", "contents": "Placental steroid synthesis from DHEAS during dexamethasone therapy. Maternal glucocorticoid treatment affects estrogen synthesis by decreasing estrogen precursors. Whether glucocorticoid has any effect on the placental conversion of estrogen precursors to estrogen is not known. A study was therefore undertaken to investigate the effect of 100 mg of intravenously administered dehydroepiandrosterone sulfate (DHEAS) on estradiol (E2), estriol (E3), and testosterone (T) serum levels. The test was conducted for 5 hours in 10 women treated with intramuscular dexamethasone and in 8 controls during the last trimester of pregnancy. The initial E2 and E3 serum concentrations were lower in women treated with dexamethasone than in controls, while T serum levels did not display any difference. Following the injection of DHEAS there was a significant increase in E2, with maximal levels reached between 1 and 3 hours after injection in both groups. Maximal levels of E2 were equal for both groups. There was no change in E3 levels after DHEAS administration in the nontreated group, while the increase in the dexamethasone group was significant. A significant rise in T, with maximal levels reached at 1 hour after infusion, was similar in both groups. It is concluded that maternal dexamethasone does not inhibit the conversion of DHEAS either to E2 in the placenta or to E3 and T."} {"id": "PMID:156322", "title": "Complications of laparoscopic sterilization. Comparison of 2 methods.", "content": "A retrospective study of 5346 cases of laparoscopic sterilization with special reference to early and late complications was undertaken. In the 6-year period from 1972 to 1978, 846 patients were sterilized by the elasticized silicone-ring technique and 4500 patients were sterilized by the electrocautery method. The electrocautery method was complicated by electrical burns in 13 cases (0.29%); 3 of these patients required bowel resections. Mechanical complications occurred in 1.6% of the Silastic-ring cases, but none of the patients required additional surgery. The Silastic-ring patients had greater postoperative abdominal pain than the electrocautery patients, but it usually abated within 48 hours. There were 15 cases of postoperative pelvic infection in the electrocautery group, and none in the Silastic-ring group. Bleeding from the mesosalpinx occurred in both groups and occurred more often with coincident suction D&C. Technical failure to perform the sterilization procedure was principally related to previous abdominal surgery. A substantial number of patients complained of menstrual irregularity and/or dysmenorrhea following these sterilization procedures. The majority of women reported unchanged or improved sexual relations. Improvement in sexual relations was reported by significantly more patients in the Silastic-ring group than in the electrocautery group.", "contents": "Complications of laparoscopic sterilization. Comparison of 2 methods. A retrospective study of 5346 cases of laparoscopic sterilization with special reference to early and late complications was undertaken. In the 6-year period from 1972 to 1978, 846 patients were sterilized by the elasticized silicone-ring technique and 4500 patients were sterilized by the electrocautery method. The electrocautery method was complicated by electrical burns in 13 cases (0.29%); 3 of these patients required bowel resections. Mechanical complications occurred in 1.6% of the Silastic-ring cases, but none of the patients required additional surgery. The Silastic-ring patients had greater postoperative abdominal pain than the electrocautery patients, but it usually abated within 48 hours. There were 15 cases of postoperative pelvic infection in the electrocautery group, and none in the Silastic-ring group. Bleeding from the mesosalpinx occurred in both groups and occurred more often with coincident suction D&C. Technical failure to perform the sterilization procedure was principally related to previous abdominal surgery. A substantial number of patients complained of menstrual irregularity and/or dysmenorrhea following these sterilization procedures. The majority of women reported unchanged or improved sexual relations. Improvement in sexual relations was reported by significantly more patients in the Silastic-ring group than in the electrocautery group."} {"id": "PMID:156343", "title": "Steroid rosacea in children.", "content": "Steroid rosacea is a facial dermatitis clinically resembling acne rosacea. Fluorinated topical steroids have been implicated as the cause or precipitating factor in previous case reports mainly involving an adult population. Four cases of pediatric acne rosacea associated with the use of topical fluorinated glucocorticosteroids are described. The process worsened during the two weeks following steroid cessation. We recommend that fluorinated glucocorticosteroids should not be used on the face of infants and children.", "contents": "Steroid rosacea in children. Steroid rosacea is a facial dermatitis clinically resembling acne rosacea. Fluorinated topical steroids have been implicated as the cause or precipitating factor in previous case reports mainly involving an adult population. Four cases of pediatric acne rosacea associated with the use of topical fluorinated glucocorticosteroids are described. The process worsened during the two weeks following steroid cessation. We recommend that fluorinated glucocorticosteroids should not be used on the face of infants and children."} {"id": "PMID:156346", "title": "Communication patterns in pedodontics.", "content": "This investigation examined communication patterns between 16 randomly selected senior dental students and their child patients. Interactions were videotaped during a regular treatment appointment and analyzed according to four Practitioner Communication categories and four Child Cooperation categories. Communication categories included Directive Guidance Behavior, Permissive Behavior, Coercive Behavior, and Other Behavior. Child behavior categories included Cooperation, Resistance, Noncooperation, and Other. The probability that a given category of child's behavior would follow a given category of practitioner's behavior was calculated. Results indicated a .85 probability that Directive Guidance would be followed by Cooperation; a .67 probability that Permissiveness would lead to Noncooperation; and a .97 likelihood that Coerciveness would lead to either Noncooperation or Resistance. Practitioners' confidence was also considered; less confident operators account for 95% of the Coercive behaviors, 86% of Permissive behaviors and 87% of Uncooperative behaviors.", "contents": "Communication patterns in pedodontics. This investigation examined communication patterns between 16 randomly selected senior dental students and their child patients. Interactions were videotaped during a regular treatment appointment and analyzed according to four Practitioner Communication categories and four Child Cooperation categories. Communication categories included Directive Guidance Behavior, Permissive Behavior, Coercive Behavior, and Other Behavior. Child behavior categories included Cooperation, Resistance, Noncooperation, and Other. The probability that a given category of child's behavior would follow a given category of practitioner's behavior was calculated. Results indicated a .85 probability that Directive Guidance would be followed by Cooperation; a .67 probability that Permissiveness would lead to Noncooperation; and a .97 likelihood that Coerciveness would lead to either Noncooperation or Resistance. Practitioners' confidence was also considered; less confident operators account for 95% of the Coercive behaviors, 86% of Permissive behaviors and 87% of Uncooperative behaviors."} {"id": "PMID:156349", "title": "DNA polymerase alpha, beta and gamma activities in ultraviolet irradiated CV-1 monkey cells.", "content": "To determine the possible role of DNA polymerase alpha, beta and gamma during the repair period following ultraviolet (lambda max : 254 nm) irradiation of monkey CV-1 cells, we measured the three enzymatic activities by using specific tests, either in crude extracts or after fractionation by sucrose gradient (5--20%) centrifugation at high salt concentration. When compared to the unirradiated control, we could not detect any significant variation in the levels of activity of DNA polymerases alpha, beta and gamma at any time (0, 12 to 48 h) after ultraviolet irradiation of the cells with doses ranging from 9 to 52.5 J.m-2.", "contents": "DNA polymerase alpha, beta and gamma activities in ultraviolet irradiated CV-1 monkey cells. To determine the possible role of DNA polymerase alpha, beta and gamma during the repair period following ultraviolet (lambda max : 254 nm) irradiation of monkey CV-1 cells, we measured the three enzymatic activities by using specific tests, either in crude extracts or after fractionation by sucrose gradient (5--20%) centrifugation at high salt concentration. When compared to the unirradiated control, we could not detect any significant variation in the levels of activity of DNA polymerases alpha, beta and gamma at any time (0, 12 to 48 h) after ultraviolet irradiation of the cells with doses ranging from 9 to 52.5 J.m-2."} {"id": "PMID:156350", "title": "Synthesis and coding properties of dinucleoside diphosphates containing alky pyrimidines which are formed by the action of carcinogens on nucleic acids.", "content": "Dinucleoside diphosphates of the general type pGpN have been prepared enzymatically using ribonuclease N1. Alkylated uridines or cytidines, which are products of carcinogens acting on nucleic acids, were tested in dinucleoside diphosphates for their ability to stimulate the binding of Ala- or Val-tRNA to ribosomes. O2-Ethyl C and 3-methyl C functioned as U, but not as C. In contrast, 3-methyl U behaved as C, but not as U. Both O2 and O4-ethyl U could be recognized as C or U, although binding in both cases was weak. Thus, modifications of the hydrogen-bonding sites of U or C causes miscoding and could be considered to represent mutagenic reactions.", "contents": "Synthesis and coding properties of dinucleoside diphosphates containing alky pyrimidines which are formed by the action of carcinogens on nucleic acids. Dinucleoside diphosphates of the general type pGpN have been prepared enzymatically using ribonuclease N1. Alkylated uridines or cytidines, which are products of carcinogens acting on nucleic acids, were tested in dinucleoside diphosphates for their ability to stimulate the binding of Ala- or Val-tRNA to ribosomes. O2-Ethyl C and 3-methyl C functioned as U, but not as C. In contrast, 3-methyl U behaved as C, but not as U. Both O2 and O4-ethyl U could be recognized as C or U, although binding in both cases was weak. Thus, modifications of the hydrogen-bonding sites of U or C causes miscoding and could be considered to represent mutagenic reactions."} {"id": "PMID:156351", "title": "Laboratory of Physiological Chemistry, State University Groningen, Netherlands.", "content": "To obtain more information about the arrangement of Hind III restriction fragments in the tRNA-rRNA region of the Neurospora crassa mitochondrial (mt) DNA we have cleaved the mtDNA with Hpa I and Hind II. We could construct additional cleavage maps for these enzymes. Hybridization of rRNAs to Hind II fragments confirmed the existence of an intervening region of about 2,300 basepairs in the 24S rRNA (Hahn et al., Cell, in press). About seven tRNA genes, among which the genes for tRNA1Ser and tRNAMetM, are located in a segment of about 5,000 bp separating the 24S and 17S rRNA genes. Another cluster of 14 tRNA genes is found adjacent to the other end of the 24S gene. The genes for tRNALeu1 and tRNAMetF are located in this cluster.", "contents": "Laboratory of Physiological Chemistry, State University Groningen, Netherlands. To obtain more information about the arrangement of Hind III restriction fragments in the tRNA-rRNA region of the Neurospora crassa mitochondrial (mt) DNA we have cleaved the mtDNA with Hpa I and Hind II. We could construct additional cleavage maps for these enzymes. Hybridization of rRNAs to Hind II fragments confirmed the existence of an intervening region of about 2,300 basepairs in the 24S rRNA (Hahn et al., Cell, in press). About seven tRNA genes, among which the genes for tRNA1Ser and tRNAMetM, are located in a segment of about 5,000 bp separating the 24S and 17S rRNA genes. Another cluster of 14 tRNA genes is found adjacent to the other end of the 24S gene. The genes for tRNALeu1 and tRNAMetF are located in this cluster."} {"id": "PMID:156360", "title": "Termination of transcription by Escherichia coli RNA polymerase: influence of secondary structure of RNA transcripts on rho-independent and rho-dependent termination.", "content": "The effect of RNA secondary structure on rho-independent and rho-dependent termination of transcription of T3 DNA by Escherichia coli RNA polymerase has been studied by incorporating, into nascent transcripts, base analogs that lead to altered base-pairing properties. A guanine --> hypoxanthine substitution, with attendant weakening of secondary structure, abolished the rho-independent termination at 20% of the genome; in contrast, replacement of cytosine with 5-bromocytosine, which forms stronger pairs with guanine, enhanced termination at this site. rho-Independent termination was not altered by replacing uracil with 5-bromouracil. There are two major rho-dependent termination sites on the T3 DNA-at 8 and 15%. The termination activity of rho in this system also depended on RNA secondary structure. The incorporation of 5-bromouracil instead of uracil into RNA did not alter the site specificity of rho action but rho was rendered inactive when cytosine was replaced by 5-bromocytosine. In contrast, replacement of GTP with ITP in the reaction increased rho-dependent inhibition of RNA synthesis, caused production of heterogeneous-sized transcripts, and stimulated rho-mediated ATP hydrolysis. The rho-associated ATPase activity, in the presence of isolated T3 RNA, was also stimulated by inosine substitution. Furthermore, the temperature-sensitive rho isolated from rho 15 mutant of E. coli, which does not terminate transcription in the presence of the common rNTPs, was active when GTP was replaced with ITP. These results suggest that strongly paired G.C-rich regions in RNA stem-loop structures or RNA.DNA hybrids are essential for rho-independent termination, whereas rho-dependent termination requires weakly paired cytosine residues for its action.", "contents": "Termination of transcription by Escherichia coli RNA polymerase: influence of secondary structure of RNA transcripts on rho-independent and rho-dependent termination. The effect of RNA secondary structure on rho-independent and rho-dependent termination of transcription of T3 DNA by Escherichia coli RNA polymerase has been studied by incorporating, into nascent transcripts, base analogs that lead to altered base-pairing properties. A guanine --> hypoxanthine substitution, with attendant weakening of secondary structure, abolished the rho-independent termination at 20% of the genome; in contrast, replacement of cytosine with 5-bromocytosine, which forms stronger pairs with guanine, enhanced termination at this site. rho-Independent termination was not altered by replacing uracil with 5-bromouracil. There are two major rho-dependent termination sites on the T3 DNA-at 8 and 15%. The termination activity of rho in this system also depended on RNA secondary structure. The incorporation of 5-bromouracil instead of uracil into RNA did not alter the site specificity of rho action but rho was rendered inactive when cytosine was replaced by 5-bromocytosine. In contrast, replacement of GTP with ITP in the reaction increased rho-dependent inhibition of RNA synthesis, caused production of heterogeneous-sized transcripts, and stimulated rho-mediated ATP hydrolysis. The rho-associated ATPase activity, in the presence of isolated T3 RNA, was also stimulated by inosine substitution. Furthermore, the temperature-sensitive rho isolated from rho 15 mutant of E. coli, which does not terminate transcription in the presence of the common rNTPs, was active when GTP was replaced with ITP. These results suggest that strongly paired G.C-rich regions in RNA stem-loop structures or RNA.DNA hybrids are essential for rho-independent termination, whereas rho-dependent termination requires weakly paired cytosine residues for its action."} {"id": "PMID:156361", "title": "Purified Escherichia coli recA protein catalyzes homologous pairing of superhelical DNA and single-stranded fragments.", "content": "Purified Escherichia coli recA protein catalyzed ATP-dependent pairing of superhelical DNA and homologous single-stranded fragments. The product of the reaction: (i) was retained by nitrocellulose filters in 1.5 M NaCl/0.15 M Na citrate at pH 7, (ii) was dissociated at pH 12.3 but was not dissociated by heating at 55 degrees C for 4 min or by treatment with 0.2% sodium dodecyl sulfate and proteinase K, (iii) contained covalently closed circular double-stranded DNA (form I DNA), (iv) contained single-stranded fragments associated with replicative form (RF) DNA, and (v) contained a significant fraction of D-loops as judged by electron microscopy. Linear and nicked circular double-stranded DNA did not substitute well for superhelical DNA; intact circular single-stranded DNA did not substitute well for single-stranded fragments. Homologous combinations of single-stranded fragments and superhelical DNA from phages phiX174 and fd reacted, whereas heterologous combinations did not. The reaction required high concentrations of protein and MgCl2. The ATPase activity of purified recA protein was more than 98% dependent on the addition of single-stranded DNA. In 1 mM MgCl2, the ability of superhelical DNA to support the ATPase activity was two-thirds as good as that of single-stranded DNA.", "contents": "Purified Escherichia coli recA protein catalyzes homologous pairing of superhelical DNA and single-stranded fragments. Purified Escherichia coli recA protein catalyzed ATP-dependent pairing of superhelical DNA and homologous single-stranded fragments. The product of the reaction: (i) was retained by nitrocellulose filters in 1.5 M NaCl/0.15 M Na citrate at pH 7, (ii) was dissociated at pH 12.3 but was not dissociated by heating at 55 degrees C for 4 min or by treatment with 0.2% sodium dodecyl sulfate and proteinase K, (iii) contained covalently closed circular double-stranded DNA (form I DNA), (iv) contained single-stranded fragments associated with replicative form (RF) DNA, and (v) contained a significant fraction of D-loops as judged by electron microscopy. Linear and nicked circular double-stranded DNA did not substitute well for superhelical DNA; intact circular single-stranded DNA did not substitute well for single-stranded fragments. Homologous combinations of single-stranded fragments and superhelical DNA from phages phiX174 and fd reacted, whereas heterologous combinations did not. The reaction required high concentrations of protein and MgCl2. The ATPase activity of purified recA protein was more than 98% dependent on the addition of single-stranded DNA. In 1 mM MgCl2, the ability of superhelical DNA to support the ATPase activity was two-thirds as good as that of single-stranded DNA."} {"id": "PMID:156362", "title": "Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity.", "content": "In an actomyosin fraction isolated from human platelets, phosphorylation of the 20,000-dalton light chain of myosin is stimulated by calcium and the calcium-binding protein calmodulin. The enzyme catalyzing this phosphorylation has been isolated by using calmodulin-affinity chromatography. Platelet myosin light chain kinase activity was monitored throughout the isolation procedures by using the 20,000-dalton smooth muscle myosin light chain purified from turkey gizzards as substrate. The partially purified myosin kinase requires both calcium and calmodulin for activity and has a specific activity of 3.1 mumol of phosphate transferred to the 20,000-dalton light chain per mg of kinase per min under optimal assay conditions. Km values determined for ATP and myosin light chains are 121 microM and 18 microM, respectively. Of several substrates surveyed as phosphate acceptors (alpha-casein, histone II-A, phosphorylase b, protamine, histone V-S, and phosvitin), only the 20,000-dalton myosin light chain is phosphorylated at a significant rate. These results suggest that platelet myosin light chain kinase is a calcium-dependent enzyme and that the requirement for calcium is mediated by the calcium-binding protein calmodulin.", "contents": "Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. In an actomyosin fraction isolated from human platelets, phosphorylation of the 20,000-dalton light chain of myosin is stimulated by calcium and the calcium-binding protein calmodulin. The enzyme catalyzing this phosphorylation has been isolated by using calmodulin-affinity chromatography. Platelet myosin light chain kinase activity was monitored throughout the isolation procedures by using the 20,000-dalton smooth muscle myosin light chain purified from turkey gizzards as substrate. The partially purified myosin kinase requires both calcium and calmodulin for activity and has a specific activity of 3.1 mumol of phosphate transferred to the 20,000-dalton light chain per mg of kinase per min under optimal assay conditions. Km values determined for ATP and myosin light chains are 121 microM and 18 microM, respectively. Of several substrates surveyed as phosphate acceptors (alpha-casein, histone II-A, phosphorylase b, protamine, histone V-S, and phosvitin), only the 20,000-dalton myosin light chain is phosphorylated at a significant rate. These results suggest that platelet myosin light chain kinase is a calcium-dependent enzyme and that the requirement for calcium is mediated by the calcium-binding protein calmodulin."} {"id": "PMID:156363", "title": "Nucleotide sequence of the mitochondrial structural gene for subunit 9 of yeast ATPase complex.", "content": "We have determined the nucleotide sequence of a segment of Saccharomyces mtDNA that contains the structural gene for one of the subunits (the dicyclohexylcarbodiimide-binding protein) of the mitochondrial ATPase complex. The sequence fits the known amino acid sequence of this protein with the exception of one amino acid. Codon usage is biased in favor of A + T-rich codons. On both sides of the gene, the nucleotide sequence contains less than 4% (mol/mol) G + C for at least 180 nucleotides; these A + T sequences show no evidence of internal repetition. The gene and all the A + T-rich sequence preceding the gene are present in a 12S RNA that is the major transcript of this segment of mtDNA. The nature of the sequences responsible for binding ribosomes to mitochondrial mRNA and for termination of RNA synthesis is considered.", "contents": "Nucleotide sequence of the mitochondrial structural gene for subunit 9 of yeast ATPase complex. We have determined the nucleotide sequence of a segment of Saccharomyces mtDNA that contains the structural gene for one of the subunits (the dicyclohexylcarbodiimide-binding protein) of the mitochondrial ATPase complex. The sequence fits the known amino acid sequence of this protein with the exception of one amino acid. Codon usage is biased in favor of A + T-rich codons. On both sides of the gene, the nucleotide sequence contains less than 4% (mol/mol) G + C for at least 180 nucleotides; these A + T sequences show no evidence of internal repetition. The gene and all the A + T-rich sequence preceding the gene are present in a 12S RNA that is the major transcript of this segment of mtDNA. The nature of the sequences responsible for binding ribosomes to mitochondrial mRNA and for termination of RNA synthesis is considered."} {"id": "PMID:156364", "title": "Inhibitory spectrum of alpha 2-plasmin inhibitor.", "content": "alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo. We have studied the effect of purified alpha 2PI upon various proteases participating in human blood coagulation and kinin generation. At physiological concentration (50 microgram/ml), alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments, the amidolytic, kininogenase, and clot-promoting activities of plasma kallikrein, and the clot-promoting properties of activated plasma thromboplastin antecedent (PTA, Factor XIa) and thrombin. alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor (Factor Xa). alpha 2PI did not inhibit the activity of activated Christmas factor (Factor IXa) or urinary kallikrein. Heparin (1.5-2.0 units/ml) did not enhance the inhibitory function of alpha 2PI. These results suggest that, like other plasma protease inhibitors, alpha 2PI possesses a broad in vitro spectrum of inhibitory properties.", "contents": "Inhibitory spectrum of alpha 2-plasmin inhibitor. alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo. We have studied the effect of purified alpha 2PI upon various proteases participating in human blood coagulation and kinin generation. At physiological concentration (50 microgram/ml), alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments, the amidolytic, kininogenase, and clot-promoting activities of plasma kallikrein, and the clot-promoting properties of activated plasma thromboplastin antecedent (PTA, Factor XIa) and thrombin. alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor (Factor Xa). alpha 2PI did not inhibit the activity of activated Christmas factor (Factor IXa) or urinary kallikrein. Heparin (1.5-2.0 units/ml) did not enhance the inhibitory function of alpha 2PI. These results suggest that, like other plasma protease inhibitors, alpha 2PI possesses a broad in vitro spectrum of inhibitory properties."} {"id": "PMID:156365", "title": "Plasmin-mediated proteolysis of casein in bovine milk.", "content": "Plasminogen was found to be present in bovine milk by crossreactivity between rabbit antiserum to plasminogen and casein prepared from milk by acid precipitation. This result was further supported by recovery of intact 125I-labeled plasminogen from rabbit milk after its intravenous injection. Freshly isolated whole bovine casein was observed to undergo slow autoproteolysis at 37 degrees C. Polyacrylamide gel electrophoresis revealed gradual disappearance of major caseins accompanied by appearance and increase in intensity of numerous electrophoretic bands. This autoproteolysis was inhibited by low concentrations of epsilon-aminocaproic acid (0.1 mM) and diisopropyl fluorophosphate (1 mM); catalytic amounts of urokinase accelerated the process. Autoproteolysis of isolated bovine beta-casein was shown by both urea and sodium dodecyl sulfate gel electrophoresis to result in formation of gamma 1- and gamma 2-caseins. Similar electrophoretic bands were formed when beta-casein was degraded by plasmin prepared from bovine blood serum. These results support the hypothesis that bovine plasmin occurs in milk and is identical to alkaline milk protease.", "contents": "Plasmin-mediated proteolysis of casein in bovine milk. Plasminogen was found to be present in bovine milk by crossreactivity between rabbit antiserum to plasminogen and casein prepared from milk by acid precipitation. This result was further supported by recovery of intact 125I-labeled plasminogen from rabbit milk after its intravenous injection. Freshly isolated whole bovine casein was observed to undergo slow autoproteolysis at 37 degrees C. Polyacrylamide gel electrophoresis revealed gradual disappearance of major caseins accompanied by appearance and increase in intensity of numerous electrophoretic bands. This autoproteolysis was inhibited by low concentrations of epsilon-aminocaproic acid (0.1 mM) and diisopropyl fluorophosphate (1 mM); catalytic amounts of urokinase accelerated the process. Autoproteolysis of isolated bovine beta-casein was shown by both urea and sodium dodecyl sulfate gel electrophoresis to result in formation of gamma 1- and gamma 2-caseins. Similar electrophoretic bands were formed when beta-casein was degraded by plasmin prepared from bovine blood serum. These results support the hypothesis that bovine plasmin occurs in milk and is identical to alkaline milk protease."} {"id": "PMID:156366", "title": "Down syndrome: gene dosage at the transcriptional level in skin fibroblasts.", "content": "Chromosome imbalance (aneusomy) is the leading known cause of both spontaneous abortion and mental retardation in human beings. The primary abnormality is thought to result from quantitative changes of transcription products from the unbalanced genetic material. To document this point, I compared chromosome 21-specific transcription in skin fibroblasts from subjects with monosomy 21, disomy 21 (normal), and trisomy 21 (Down syndrome). Polyadenylylated RNA [poly(A)-RNA], which is enriched in messenger and messenger-precursor RNA sequences, was isolated from the above fibroblast lines. Radioactive DNA (cDNA) complementary to these RNAs was synthesized with reverse transcriptase (RNA-dependent DNA polymerase). These cDNAs were hybridized with (i) DNA from a cell line with a mouse genome plus human chromosome 21 and (ii) mouse DNA. Subtraction of the amount of hybridization in experiment ii from that in experiment i yielded a measure of human chromosome 21-specific RNA sequences. The results were consistent with gene dosage at the transcriptional level; for monosomy 21-derived cDNA, 0.6% (of the total cDNA) hybridized specifically to human chromosome 21; for disomy 21-derived cDNA, 2% hybridized; and for trisomy 21-derived cDNA, 3% hybridized. Thus, for DNA sequences on chromosome 21 in human skin fibroblasts, transcription depends on DNA dosage. Characterization of the chromosome 21-specific RNA sequences quantitated in these experiments could help to elucidate the mechanisms by which abnormal karyotypes result in abnormal phenotypes.", "contents": "Down syndrome: gene dosage at the transcriptional level in skin fibroblasts. Chromosome imbalance (aneusomy) is the leading known cause of both spontaneous abortion and mental retardation in human beings. The primary abnormality is thought to result from quantitative changes of transcription products from the unbalanced genetic material. To document this point, I compared chromosome 21-specific transcription in skin fibroblasts from subjects with monosomy 21, disomy 21 (normal), and trisomy 21 (Down syndrome). Polyadenylylated RNA [poly(A)-RNA], which is enriched in messenger and messenger-precursor RNA sequences, was isolated from the above fibroblast lines. Radioactive DNA (cDNA) complementary to these RNAs was synthesized with reverse transcriptase (RNA-dependent DNA polymerase). These cDNAs were hybridized with (i) DNA from a cell line with a mouse genome plus human chromosome 21 and (ii) mouse DNA. Subtraction of the amount of hybridization in experiment ii from that in experiment i yielded a measure of human chromosome 21-specific RNA sequences. The results were consistent with gene dosage at the transcriptional level; for monosomy 21-derived cDNA, 0.6% (of the total cDNA) hybridized specifically to human chromosome 21; for disomy 21-derived cDNA, 2% hybridized; and for trisomy 21-derived cDNA, 3% hybridized. Thus, for DNA sequences on chromosome 21 in human skin fibroblasts, transcription depends on DNA dosage. Characterization of the chromosome 21-specific RNA sequences quantitated in these experiments could help to elucidate the mechanisms by which abnormal karyotypes result in abnormal phenotypes."} {"id": "PMID:156367", "title": "Molecular signals for initiating protein synthesis in organ hypertrophy.", "content": "When chronically provoked to increased physiologic activity, organs increase in mass through augmented protein protein synthesis. This process of compensatory hypertrophy can involve cell division as well as cell growth. To test for molecules that might regulate organ size, by inducing hypertrophy, we performed a series of experiments using isolated, perfused, canine hearts in which the left ventricle was beating but performed no work. Hypertrophying hearts and kidneys as well as normal control organs were extracted and the extracts were perfused through isolated heart preparations. Before and after perfusion, RNA was extracted from fragments of the isolated hearts and translated in cell-free media containing [35S]methionine. Incorporation of methionine into protein was measured by liquid scintillation spectrometry. When perfused through normal hearts, extracts from hypertrophying heart and kidney were able to increase greatly the translational ability of RNA extracted from the normal hearts; corresponding perfusates from nonhypertrophying hearts and kidneys had no effect. Our results indicate that molecules that initiate hypertrophic organ growth are extractable, are generated by the cells of the organ under stress, and are probably similar in heart and kidney and perhaps in many other organs as well.", "contents": "Molecular signals for initiating protein synthesis in organ hypertrophy. When chronically provoked to increased physiologic activity, organs increase in mass through augmented protein protein synthesis. This process of compensatory hypertrophy can involve cell division as well as cell growth. To test for molecules that might regulate organ size, by inducing hypertrophy, we performed a series of experiments using isolated, perfused, canine hearts in which the left ventricle was beating but performed no work. Hypertrophying hearts and kidneys as well as normal control organs were extracted and the extracts were perfused through isolated heart preparations. Before and after perfusion, RNA was extracted from fragments of the isolated hearts and translated in cell-free media containing [35S]methionine. Incorporation of methionine into protein was measured by liquid scintillation spectrometry. When perfused through normal hearts, extracts from hypertrophying heart and kidney were able to increase greatly the translational ability of RNA extracted from the normal hearts; corresponding perfusates from nonhypertrophying hearts and kidneys had no effect. Our results indicate that molecules that initiate hypertrophic organ growth are extractable, are generated by the cells of the organ under stress, and are probably similar in heart and kidney and perhaps in many other organs as well."} {"id": "PMID:156369", "title": "Effect of alpha-methyltryptamine on spontaneous activity in mice.", "content": "A standard dose of 10 mg/kg (48 mu mole/kg) of (+/-)-alpha-methyltryptamine (AMT) induced a significant and long lasting increase in spontaneous activity in mice. Pretreatment of mice with either pimozide or alpha-methyl-para-tyrosine methyl ester HCl (AMPT) prevented the activity increase induced by AMT. In similar trials, methysergide or para-chlorophenylalanine (PCPA) were also found to antagonize the development of hyperactivity following a standard dose of AMT. The results suggest that both endogenous dopamine and serotonin many participate in the hyperactivity induced by AMT.", "contents": "Effect of alpha-methyltryptamine on spontaneous activity in mice. A standard dose of 10 mg/kg (48 mu mole/kg) of (+/-)-alpha-methyltryptamine (AMT) induced a significant and long lasting increase in spontaneous activity in mice. Pretreatment of mice with either pimozide or alpha-methyl-para-tyrosine methyl ester HCl (AMPT) prevented the activity increase induced by AMT. In similar trials, methysergide or para-chlorophenylalanine (PCPA) were also found to antagonize the development of hyperactivity following a standard dose of AMT. The results suggest that both endogenous dopamine and serotonin many participate in the hyperactivity induced by AMT."} {"id": "PMID:156370", "title": "Mediation of footshock sensitivity by serotonergic projection to hippocampus.", "content": "The present experiments assessed the effects of changes in serotonergic function on footshock sensitivity, as determined by a quantified version of the flinch-jump assessment method. In Experiment 1, depletion of telencephalic serotonin by PCPA injection, medial forebrain bundle lesion, or septal lesion, produced increases in reactivity which were correlated with reductions in telencephalic serotonin levels. In all cases, this increased sensitivity was reversed by injections of d, 1-5-hydroxytryptophan (5-HTP) which restored telencephalic serotonin levels to normal. This effect of 5-HTP had not previously been demonstrated in septal lesioned animals, and overall levels of reactivity of septal animals to other stimuli were also reduced by 5-HTP. Experiment 2 tested the effects of hippocampal lesion on the 5-HTP effect in animals when serotonin depletion produced by either PCPA or septal lesion. Hippocampal lesion, while not increasing footshock sensitivity further, significantly attenuated the effectiveness of 5-HTP in restoring sensitivity to normal. The results suggest that hippocampus may be an important site of action of serotonin in modulating reactivity to footshock, and that failure of raphe lesions to increase reactivity may be due to failure to adequately deplete hippocampal serotonin.", "contents": "Mediation of footshock sensitivity by serotonergic projection to hippocampus. The present experiments assessed the effects of changes in serotonergic function on footshock sensitivity, as determined by a quantified version of the flinch-jump assessment method. In Experiment 1, depletion of telencephalic serotonin by PCPA injection, medial forebrain bundle lesion, or septal lesion, produced increases in reactivity which were correlated with reductions in telencephalic serotonin levels. In all cases, this increased sensitivity was reversed by injections of d, 1-5-hydroxytryptophan (5-HTP) which restored telencephalic serotonin levels to normal. This effect of 5-HTP had not previously been demonstrated in septal lesioned animals, and overall levels of reactivity of septal animals to other stimuli were also reduced by 5-HTP. Experiment 2 tested the effects of hippocampal lesion on the 5-HTP effect in animals when serotonin depletion produced by either PCPA or septal lesion. Hippocampal lesion, while not increasing footshock sensitivity further, significantly attenuated the effectiveness of 5-HTP in restoring sensitivity to normal. The results suggest that hippocampus may be an important site of action of serotonin in modulating reactivity to footshock, and that failure of raphe lesions to increase reactivity may be due to failure to adequately deplete hippocampal serotonin."} {"id": "PMID:156371", "title": "[Synthetic inhibitors of serine proteinases. Part 19: On the inhibitory effect of amidinobenzylidene derivatives of benzo-condensed cycloalkanones on trypsin, plasmin and thrombin (author's transl)].", "content": "Amidinobenzylidene derivatives of benzo-condensed cycloalkanones proved to be potent competitive inhibitors of thrombin and trypsin. On the contrary, the antiplasmin effect of these derivatives is considerably less marked. The conversion of 3-amidinochalcone to derivatives in which the carbonyl group is incorporated into a ring, does not lead to fundamental changes in the inhibitory effect on trypsin and thrombin, whereas the antiplasmin effect decreases. Compared to 4-amidinochalcone, the 2-(4-amidinobenzylidene) derivatives of indanone-(1) and tetralone-(1) exert a stronger inhibitory effect on trypsin and thrombin. The introduction of a hetero-atom to the cycloalkanone component affected the inhibitory effect on trypsin and thrombin but insignificantly. From these results it is concluded that also in amidinobenzylidene derivatives of benzo-condensed cycloalkanone derivatives, the carbonyl function shares in enzyme-inhibitor binding.", "contents": "[Synthetic inhibitors of serine proteinases. Part 19: On the inhibitory effect of amidinobenzylidene derivatives of benzo-condensed cycloalkanones on trypsin, plasmin and thrombin (author's transl)]. Amidinobenzylidene derivatives of benzo-condensed cycloalkanones proved to be potent competitive inhibitors of thrombin and trypsin. On the contrary, the antiplasmin effect of these derivatives is considerably less marked. The conversion of 3-amidinochalcone to derivatives in which the carbonyl group is incorporated into a ring, does not lead to fundamental changes in the inhibitory effect on trypsin and thrombin, whereas the antiplasmin effect decreases. Compared to 4-amidinochalcone, the 2-(4-amidinobenzylidene) derivatives of indanone-(1) and tetralone-(1) exert a stronger inhibitory effect on trypsin and thrombin. The introduction of a hetero-atom to the cycloalkanone component affected the inhibitory effect on trypsin and thrombin but insignificantly. From these results it is concluded that also in amidinobenzylidene derivatives of benzo-condensed cycloalkanone derivatives, the carbonyl function shares in enzyme-inhibitor binding."} {"id": "PMID:156373", "title": "Effects of brain serotonin alterations on hypothermia produced by chlorpromazine in rats.", "content": "Depressing functional serotonin or depleting serotonin levels in rat brains with either p-chlorophenylalanine, 5,6-dihydroxytryptamine or raphe lesions greatly enhanced hypothermia induced by chloropromazine (CPZ). Depressing the firing of raphe units or decreasing serotonin turnover in the brain with either a serotonin precursor (tryptophan) or the inhibitors of serotonin re-uptake (Lilly 1 10140 and chlorimipramine) also greatly enhanced the CPZ-induced hypothermia. The data indicate that serotonergic activity in the brain plays a role in the elaboration or modulation of CPZ hypothermia.", "contents": "Effects of brain serotonin alterations on hypothermia produced by chlorpromazine in rats. Depressing functional serotonin or depleting serotonin levels in rat brains with either p-chlorophenylalanine, 5,6-dihydroxytryptamine or raphe lesions greatly enhanced hypothermia induced by chloropromazine (CPZ). Depressing the firing of raphe units or decreasing serotonin turnover in the brain with either a serotonin precursor (tryptophan) or the inhibitors of serotonin re-uptake (Lilly 1 10140 and chlorimipramine) also greatly enhanced the CPZ-induced hypothermia. The data indicate that serotonergic activity in the brain plays a role in the elaboration or modulation of CPZ hypothermia."} {"id": "PMID:156374", "title": "The \"fakeability\" of the attitudes toward disabled persons scale: form B.", "content": "The purpose of this study was to provide evidence for or against the \"fakeability\" of the Attitudes Toward Disabled Persons Scale: Form B. Form B of the Scale was administered to 25 women, between the ages of 19 and 24, studying at a midwestern university. Seven days later, the subjects retook the test and were instructed to fake their answers so that they would receive a higher score. The difference between the true scores and the fake scores were not found to be significant, and it was concluded that the Attitudes Toward Disabled Persons Scale: Form B is not \"fakeable.\"", "contents": "The \"fakeability\" of the attitudes toward disabled persons scale: form B. The purpose of this study was to provide evidence for or against the \"fakeability\" of the Attitudes Toward Disabled Persons Scale: Form B. Form B of the Scale was administered to 25 women, between the ages of 19 and 24, studying at a midwestern university. Seven days later, the subjects retook the test and were instructed to fake their answers so that they would receive a higher score. The difference between the true scores and the fake scores were not found to be significant, and it was concluded that the Attitudes Toward Disabled Persons Scale: Form B is not \"fakeable.\""} {"id": "PMID:156378", "title": "Two unusual umbilicoplasties.", "content": "We describe the creation of an umbilicus where none previously existed, during an abdominoplasty, and the cosmetic shaping of a stretched umbilicus after an umbilical hernia repair.", "contents": "Two unusual umbilicoplasties. We describe the creation of an umbilicus where none previously existed, during an abdominoplasty, and the cosmetic shaping of a stretched umbilicus after an umbilical hernia repair."} {"id": "PMID:156380", "title": "Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse.", "content": "The ability of delta 9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8 alpha, 11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E1 (PGE1) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED50 in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED50 range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE1 as the nociceptive agent, 11-OH THC was equipotent to THC while 8 alpha, 11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.", "contents": "Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse. The ability of delta 9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8 alpha, 11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E1 (PGE1) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED50 in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED50 range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE1 as the nociceptive agent, 11-OH THC was equipotent to THC while 8 alpha, 11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN."} {"id": "PMID:156381", "title": "Hepatitis-B surface antigen and antibody: prevalence and persistence in institutionalized and noninstitutionalized persons.", "content": "A total of 426 persons were studied in an attempt to more clearly define the high prevalence of hepatitis-B surface antigen (HBsAg) seen among institutionalized persons. HBsAg was found in 63.4 percent of the children and young adults with Down's syndrome (DS) at the Central Wisconsin Center (CWC) and in 45.5 percent of those at the Northern Wisconsin Center (NWC). Significantly more subjects with DS had hepatitis-B antigenemia than age- and sex-matched non-DS institutionalized subjects. Antibody (anti-HBs) to HBsAg was found in 19.5 percent of the DS subjects at CWC and in 38.6 percent of those at NWC. The prevalence of anti-HBs was similar among DS and non-DS institutionalized subjects. None of the noninstitutionalized subjects had HBsAg in their serums and their anti-HBs prevalence was low (2.1 percent). HBsAg was found to persist for at least 10 years in both DS and non-DS institutionalized subjects. However, persistence occurred more frequently among DS subjects. Anti-HBs persisted at least 10 years among non-DS subjects, but DS subjects tended to lose antibody sooner. The study findings indicated that the high prevalence of HBsAg seen in institutionalized DS subjects at CWC and NWC were not related to the age of the subject at admission nor to the duration of institutionalization.", "contents": "Hepatitis-B surface antigen and antibody: prevalence and persistence in institutionalized and noninstitutionalized persons. A total of 426 persons were studied in an attempt to more clearly define the high prevalence of hepatitis-B surface antigen (HBsAg) seen among institutionalized persons. HBsAg was found in 63.4 percent of the children and young adults with Down's syndrome (DS) at the Central Wisconsin Center (CWC) and in 45.5 percent of those at the Northern Wisconsin Center (NWC). Significantly more subjects with DS had hepatitis-B antigenemia than age- and sex-matched non-DS institutionalized subjects. Antibody (anti-HBs) to HBsAg was found in 19.5 percent of the DS subjects at CWC and in 38.6 percent of those at NWC. The prevalence of anti-HBs was similar among DS and non-DS institutionalized subjects. None of the noninstitutionalized subjects had HBsAg in their serums and their anti-HBs prevalence was low (2.1 percent). HBsAg was found to persist for at least 10 years in both DS and non-DS institutionalized subjects. However, persistence occurred more frequently among DS subjects. Anti-HBs persisted at least 10 years among non-DS subjects, but DS subjects tended to lose antibody sooner. The study findings indicated that the high prevalence of HBsAg seen in institutionalized DS subjects at CWC and NWC were not related to the age of the subject at admission nor to the duration of institutionalization."} {"id": "PMID:156383", "title": "[Severe fractures of the lower end of the humerus in adults (author's transl)].", "content": "The authors have treated sixty six cases of severe comminuted fracture of the lower end of the humerus. Five main types have been distinguished: 1. Supracondylar fractures. 2. T-shaped fractures. 3. Trans-condylar fractures in which the fracture line is distal, detaching only the articular surfaces. 4. Diaphyso-epiphysial fractures. 5. Trans-columnar fractures similar to transcondylar fractures but with additional fractures detaching a fragment of lateral or medial epicondyle and a fracture through the trochlea separating the articular surface into two parts. Fifty-four patients were operated on to apply internal fixation. Analysis of the results based on critical criteria shows 53 p. 100 of satisfactory results. The authors emphasise the frequency and severity of damage to the ulnar nerve. They conclude that the results are better after surgical treatment than with conservative treatment which should be reserved for distal and comminuted fractures. A new type of plate has been designed to be applied and fixed to the lateral aspect of the bone.", "contents": "[Severe fractures of the lower end of the humerus in adults (author's transl)]. The authors have treated sixty six cases of severe comminuted fracture of the lower end of the humerus. Five main types have been distinguished: 1. Supracondylar fractures. 2. T-shaped fractures. 3. Trans-condylar fractures in which the fracture line is distal, detaching only the articular surfaces. 4. Diaphyso-epiphysial fractures. 5. Trans-columnar fractures similar to transcondylar fractures but with additional fractures detaching a fragment of lateral or medial epicondyle and a fracture through the trochlea separating the articular surface into two parts. Fifty-four patients were operated on to apply internal fixation. Analysis of the results based on critical criteria shows 53 p. 100 of satisfactory results. The authors emphasise the frequency and severity of damage to the ulnar nerve. They conclude that the results are better after surgical treatment than with conservative treatment which should be reserved for distal and comminuted fractures. A new type of plate has been designed to be applied and fixed to the lateral aspect of the bone."} {"id": "PMID:156384", "title": "[The patello-femoral joint in osteoarthritis of the knee with genu varum (author's transl)].", "content": "The authors have treated 63 knees with osteoarthritis associated with varus deformity by valgus osteotomies. The clinical and radiological state of the patello-femoral joints has been studied before and after correction of varus deformity. No correlation was found between the severity of tibio-femoral osteoarthritis and patello-femoral osteoarthritis. Medial patello-femoral discordance was found in 12 p. 100 of the cases. Clinical evidence of pain arising from the patello-femoral joint was more often found than evidence of radiological abnormality. It is concluded that pain arising from the medial compartment may be confused with patellofemoral pain. A five-year follow-up showed that the patello-femoral joint was not influenced radiologically by the valgus osteotomy but patellar pain was improved in most of the cases. Procedures to re-align the patella should not normally be associated with valgus osteotomy in cases in which patellar pain exists in association with osteoarthritis of the knee with varus deformity.", "contents": "[The patello-femoral joint in osteoarthritis of the knee with genu varum (author's transl)]. The authors have treated 63 knees with osteoarthritis associated with varus deformity by valgus osteotomies. The clinical and radiological state of the patello-femoral joints has been studied before and after correction of varus deformity. No correlation was found between the severity of tibio-femoral osteoarthritis and patello-femoral osteoarthritis. Medial patello-femoral discordance was found in 12 p. 100 of the cases. Clinical evidence of pain arising from the patello-femoral joint was more often found than evidence of radiological abnormality. It is concluded that pain arising from the medial compartment may be confused with patellofemoral pain. A five-year follow-up showed that the patello-femoral joint was not influenced radiologically by the valgus osteotomy but patellar pain was improved in most of the cases. Procedures to re-align the patella should not normally be associated with valgus osteotomy in cases in which patellar pain exists in association with osteoarthritis of the knee with varus deformity."} {"id": "PMID:156390", "title": "Cimetidine fails to block functional antagonism of carbachol by histamine in rat trachea.", "content": "Histamine and dimaprit functionally antagonised the ability of carbachol to constrict the rat trachea in the presence of mepyramine. Cimetidine did not block the functional antagonism of histamine or dimaprit for carbachol.", "contents": "Cimetidine fails to block functional antagonism of carbachol by histamine in rat trachea. Histamine and dimaprit functionally antagonised the ability of carbachol to constrict the rat trachea in the presence of mepyramine. Cimetidine did not block the functional antagonism of histamine or dimaprit for carbachol."} {"id": "PMID:156391", "title": "A prospective study of low back pain.", "content": "Consecutive patients attending hospital for the first time with backache were entered into a prospective study, provided that certain defined causes (infective, neoplastic, metabolic and inflammatory etc.) were not apparent at the first visit. Amongst 188 available for analysis, 65% were discharged and 28% defaulted, together making a total of 93% who 'recovered uneventfully' (in the sense that they were no longer attending hospital) on average in about three months, 4% came to 'myelography' (radiculography using Dimer-X or Amipaque) including 2% to discectomy, 1.5% proved to have treatable underlying diseases accounting for their backache while 1.5% became 'chronic attenders'. Information available at the first visit (patient characteristics, history, examination, radiographs and psychological questionnaire) provided few pointers to what the outcome would be or how long the patient would attend hospital. In particular, routine X-ray examination did not provide clues to any important conditions not already suspected by the clinicians. A case is made for reserving routine radiography for patients who have not recovered within about three months.", "contents": "A prospective study of low back pain. Consecutive patients attending hospital for the first time with backache were entered into a prospective study, provided that certain defined causes (infective, neoplastic, metabolic and inflammatory etc.) were not apparent at the first visit. Amongst 188 available for analysis, 65% were discharged and 28% defaulted, together making a total of 93% who 'recovered uneventfully' (in the sense that they were no longer attending hospital) on average in about three months, 4% came to 'myelography' (radiculography using Dimer-X or Amipaque) including 2% to discectomy, 1.5% proved to have treatable underlying diseases accounting for their backache while 1.5% became 'chronic attenders'. Information available at the first visit (patient characteristics, history, examination, radiographs and psychological questionnaire) provided few pointers to what the outcome would be or how long the patient would attend hospital. In particular, routine X-ray examination did not provide clues to any important conditions not already suspected by the clinicians. A case is made for reserving routine radiography for patients who have not recovered within about three months."} {"id": "PMID:156386", "title": "[Bacteriophage therapy of septic complications of orthopaedic surgery (author's transl].", "content": "Seven septic cases have been treated by bacteriophage; two infections after insertion of a hip prosthesis, two septic arthritis of the knee, one osteomyelitis of the tibia, one septic non-union of the femur and one septic complication following Harrington rodding. Only specific phages were used in association with several types of surgical procedure. The technique of treatment is described. All cases were long-term infections with resistant organisms. Results were good in five, fair in one and one case was a failure. It is concluded that phage therapy may be helpful in the treatment of long-term infections.", "contents": "[Bacteriophage therapy of septic complications of orthopaedic surgery (author's transl]. Seven septic cases have been treated by bacteriophage; two infections after insertion of a hip prosthesis, two septic arthritis of the knee, one osteomyelitis of the tibia, one septic non-union of the femur and one septic complication following Harrington rodding. Only specific phages were used in association with several types of surgical procedure. The technique of treatment is described. All cases were long-term infections with resistant organisms. Results were good in five, fair in one and one case was a failure. It is concluded that phage therapy may be helpful in the treatment of long-term infections."} {"id": "PMID:156387", "title": "[Mycobacterium fortuitum infection after total hip prosthesis. A report of 3 cases (author's transl)].", "content": "The authors have observed three instances of sepsis due to Mycobacterium fortuitum complicating total hip replacement for osteoarthritis. The case histories are fully described. The requirements are given for recognition of the organism which grows on special culture media and which may be mistaken for Mycobacterium tuberculosis. This feature explains why, in some cases, the organism may not be discovered. Antibiotics were ineffective but the general condition of the patient was not greatly affected.", "contents": "[Mycobacterium fortuitum infection after total hip prosthesis. A report of 3 cases (author's transl)]. The authors have observed three instances of sepsis due to Mycobacterium fortuitum complicating total hip replacement for osteoarthritis. The case histories are fully described. The requirements are given for recognition of the organism which grows on special culture media and which may be mistaken for Mycobacterium tuberculosis. This feature explains why, in some cases, the organism may not be discovered. Antibiotics were ineffective but the general condition of the patient was not greatly affected."} {"id": "PMID:156392", "title": "Incidence of post burn hypertensive crisis in patients admitted to two burn centers and a community hospital in the United States.", "content": "Fortynine patients of 193 admitted (25%) with second and third degree burns to 3 hospitals in different geographical areas of the United States developed a hypertensive crisis within three to four days after admission. The crisis usually lasted from 5 days to about two weeks. Serum sodium levels decreased significantly in hypertensive patients one or two days before the peak of the hypertensive crisis and, in the Center where it was measured, plasma renin activity increased in an opposite trend to the fall of sodium. BUN and creatinine reached their highest levels in hypertensive patients two days after the peak of the crisis. Autopsies were performed on 23 patients who succumbed to the injury: eleven of them (48%) were hypertensive and had marked hypertrophy of left and right heart ventricles and of the adrenal glands when compared to the normotensive burn subjects. The cells of the zona fasciculata and the zona glomerulosa of the adrenal glands were very compact at histologic examination thus suggesting hyperactivity. This data shows that the incidence of hypertension in burn subjects is twice as high as that of the US population. Further studies of the renin-angiotensin-aldosterone system and the adrenal cortical function are indicated by the changes in plasma renin activity and the glandular weight and morphology seen at autopsy.", "contents": "Incidence of post burn hypertensive crisis in patients admitted to two burn centers and a community hospital in the United States. Fortynine patients of 193 admitted (25%) with second and third degree burns to 3 hospitals in different geographical areas of the United States developed a hypertensive crisis within three to four days after admission. The crisis usually lasted from 5 days to about two weeks. Serum sodium levels decreased significantly in hypertensive patients one or two days before the peak of the hypertensive crisis and, in the Center where it was measured, plasma renin activity increased in an opposite trend to the fall of sodium. BUN and creatinine reached their highest levels in hypertensive patients two days after the peak of the crisis. Autopsies were performed on 23 patients who succumbed to the injury: eleven of them (48%) were hypertensive and had marked hypertrophy of left and right heart ventricles and of the adrenal glands when compared to the normotensive burn subjects. The cells of the zona fasciculata and the zona glomerulosa of the adrenal glands were very compact at histologic examination thus suggesting hyperactivity. This data shows that the incidence of hypertension in burn subjects is twice as high as that of the US population. Further studies of the renin-angiotensin-aldosterone system and the adrenal cortical function are indicated by the changes in plasma renin activity and the glandular weight and morphology seen at autopsy."} {"id": "PMID:156388", "title": "[Humerus varus congenitus (author's transl)].", "content": "Two cases of humerus varus congenitus have been treated by lengthening of the humerus using an external distraction device. The first was lengthened by about 6 centimetres and the second by about four centimetres. In one case, primary bone union was obtained and in the second, secondary grafting had to be done. The clinical results were satisfactory.", "contents": "[Humerus varus congenitus (author's transl)]. Two cases of humerus varus congenitus have been treated by lengthening of the humerus using an external distraction device. The first was lengthened by about 6 centimetres and the second by about four centimetres. In one case, primary bone union was obtained and in the second, secondary grafting had to be done. The clinical results were satisfactory."} {"id": "PMID:156393", "title": "Penicillamine in rheumatoid arthritis: adverse effects.", "content": "The use of penicillamine in rheumatoid arthritis (RA) is limited by the incidence of adverse effects, some of which are potentially hazardous. However, adverse effects are dose-related and the advantages and disadvantages of different fixed and flexible dose regimes are discussed. The incidence of adverse effects is significantly greater in patients previously treated with gold who developed toxicity to that drug--no such increase being found in gold treated patients whose only reason for stopping gold was ineffectiveness. Rashes which develop after several months of treatment are variants of pemphigus and their various presentations are described. Fatal reactions, fortunately rare, are predominantly associated with aplasia of the bone marrow. Monthly haematological checks coupled with meticulous charting of the results may reveal trends as well as numerical changes and serve as an early warning of marrow damage.", "contents": "Penicillamine in rheumatoid arthritis: adverse effects. The use of penicillamine in rheumatoid arthritis (RA) is limited by the incidence of adverse effects, some of which are potentially hazardous. However, adverse effects are dose-related and the advantages and disadvantages of different fixed and flexible dose regimes are discussed. The incidence of adverse effects is significantly greater in patients previously treated with gold who developed toxicity to that drug--no such increase being found in gold treated patients whose only reason for stopping gold was ineffectiveness. Rashes which develop after several months of treatment are variants of pemphigus and their various presentations are described. Fatal reactions, fortunately rare, are predominantly associated with aplasia of the bone marrow. Monthly haematological checks coupled with meticulous charting of the results may reveal trends as well as numerical changes and serve as an early warning of marrow damage."} {"id": "PMID:156389", "title": "[Ununited fractures of the femoral neck treated by cervicocephalic impaction. A report of two cases (author's transl)].", "content": "The cases of ununited fracture of the femoral neck, treated by a technique described by Brackett (1927) and modified by Merle d'Aubign\u00e9 (1968) are reported. The femoral head was partly evacuated, care being taken to preserve its blood supply and then impacted onto the femoral neck. The results were found to be satisfactory.", "contents": "[Ununited fractures of the femoral neck treated by cervicocephalic impaction. A report of two cases (author's transl)]. The cases of ununited fracture of the femoral neck, treated by a technique described by Brackett (1927) and modified by Merle d'Aubign\u00e9 (1968) are reported. The femoral head was partly evacuated, care being taken to preserve its blood supply and then impacted onto the femoral neck. The results were found to be satisfactory."} {"id": "PMID:156394", "title": "Hypothesis for the pathogenesis of sodium aurothiomalate (Myocrisin) induced immune complex nephritis.", "content": "Renal complications associated with gold salt treatment in rheumatoid arthritis occur in fewer than 5% of treated patients. Recent investigations have shown that the renal lesion manifested clinically as membranous glomerulonephritis is caused by immune complexes. This paper presents a hypothesis for the mechanism by which gold causes this lesion: autoimmunization due to released tubular antigen(s). This hypothetical mechanism is strikingly similar to that responsible for autologous autoimmune nephrosis in the rat (Heymann's nephritis).", "contents": "Hypothesis for the pathogenesis of sodium aurothiomalate (Myocrisin) induced immune complex nephritis. Renal complications associated with gold salt treatment in rheumatoid arthritis occur in fewer than 5% of treated patients. Recent investigations have shown that the renal lesion manifested clinically as membranous glomerulonephritis is caused by immune complexes. This paper presents a hypothesis for the mechanism by which gold causes this lesion: autoimmunization due to released tubular antigen(s). This hypothetical mechanism is strikingly similar to that responsible for autologous autoimmune nephrosis in the rat (Heymann's nephritis)."} {"id": "PMID:156395", "title": "[Targeted heart fluoroscopy in radiologic and internistic practice].", "content": "Fluoroscopic examination of the heart requires a special technique if it is to provide useful diagnostic information. Information can be obtained regarding coronary calcifications, slight enlargement of a heart chamber or great vessel, localization and extension of abnormal contours within the heart shadow, pulsatory phenomena at the heart border or the great vessels, and functional changes of lung structures during respiration. This information may be decisive for the further evaluation or treatment of the patient.", "contents": "[Targeted heart fluoroscopy in radiologic and internistic practice]. Fluoroscopic examination of the heart requires a special technique if it is to provide useful diagnostic information. Information can be obtained regarding coronary calcifications, slight enlargement of a heart chamber or great vessel, localization and extension of abnormal contours within the heart shadow, pulsatory phenomena at the heart border or the great vessels, and functional changes of lung structures during respiration. This information may be decisive for the further evaluation or treatment of the patient."} {"id": "PMID:156396", "title": "Non-inactivation of an x-chromosome locus in man.", "content": "Cloned fibroblasts from women heterozygous for X-linked ichthyosis (steroid sulfatase deficiency) were examined to see whether or not this locus is subject to X-inactivation. Of 103 clones examined, all had normal levels of steroid sulfatase activity. Two of the women studied were also heterozygous for glucose-6-phosphate dehydrogenase deficiency. This allowed the demonstration that both X chromosomes were represented as the active X in various clones and that selection did not account for these findings. Thus, the steroid sulfatase locus, like the Xga locus to which it is linked, appears to escape X-inactivation in man.", "contents": "Non-inactivation of an x-chromosome locus in man. Cloned fibroblasts from women heterozygous for X-linked ichthyosis (steroid sulfatase deficiency) were examined to see whether or not this locus is subject to X-inactivation. Of 103 clones examined, all had normal levels of steroid sulfatase activity. Two of the women studied were also heterozygous for glucose-6-phosphate dehydrogenase deficiency. This allowed the demonstration that both X chromosomes were represented as the active X in various clones and that selection did not account for these findings. Thus, the steroid sulfatase locus, like the Xga locus to which it is linked, appears to escape X-inactivation in man."} {"id": "PMID:156397", "title": "Chemotherapy of parasitic worms: new biochemical strategies.", "content": "Many chemotherapeutic agents that are effective against parasitic helminths affect cellular regulatory sites that control motility, metabolism, chemotaxis, and egg formation. Serotonin receptors are present in several species of parasitic flatworms and appear to participate in the regulation of motility and carbohydrate metabolism. In Fasciola hepatica these receptors are coupled to an adenylate cyclase through a cellular component that requires guanosine triphosphate. Serotonin is the most potent indoleamine agonist, while lysergic acid diethylamide and its 2-bromo derivative are the most potent antagonists. These studies are revealing additional sites in trematodes that may be important for the development of new and more selective chemotherapeutic agents.", "contents": "Chemotherapy of parasitic worms: new biochemical strategies. Many chemotherapeutic agents that are effective against parasitic helminths affect cellular regulatory sites that control motility, metabolism, chemotaxis, and egg formation. Serotonin receptors are present in several species of parasitic flatworms and appear to participate in the regulation of motility and carbohydrate metabolism. In Fasciola hepatica these receptors are coupled to an adenylate cyclase through a cellular component that requires guanosine triphosphate. Serotonin is the most potent indoleamine agonist, while lysergic acid diethylamide and its 2-bromo derivative are the most potent antagonists. These studies are revealing additional sites in trematodes that may be important for the development of new and more selective chemotherapeutic agents."} {"id": "PMID:156398", "title": "Exfoliative dermatitis: presenting sign of internal malignancy.", "content": "Exfoliative dermatitis is most commonly associated with antecedent cutaneous disorders, medications, and lymphoreticular malignancies. Three patients with exfoliative dermatitis associated with internal carcinoma are described. The importance of thorough evaluation of all patients who present with exfoliative dermatitis is stressed.", "contents": "Exfoliative dermatitis: presenting sign of internal malignancy. Exfoliative dermatitis is most commonly associated with antecedent cutaneous disorders, medications, and lymphoreticular malignancies. Three patients with exfoliative dermatitis associated with internal carcinoma are described. The importance of thorough evaluation of all patients who present with exfoliative dermatitis is stressed."} {"id": "PMID:156404", "title": "Complications and follow-up of gastroschisis.", "content": "Twenty-seven patients with gastroschisis were seen at the Red Cross War Memorial Children's Hospital between 1960 and 1977. Twenty-five children were operated on either by primary closure, by skin closure alone, or by the insertion of a reinforced Silastic pouch or patch. The mortality rate has been reduced from 62% to 33% over the past 6 years. Despite better metabolic and respiratory care and intravenous alimentation, serious complications still occur, particularly when prematurity and associated anomalies such as atresia or meconium ileus exist. Other problems were respiratory complications, ileus, perforation, gangrene, intestinal obstruction, enterocolitis and disaccharide intolerance. The long-term follow-up of some of these patients is described.", "contents": "Complications and follow-up of gastroschisis. Twenty-seven patients with gastroschisis were seen at the Red Cross War Memorial Children's Hospital between 1960 and 1977. Twenty-five children were operated on either by primary closure, by skin closure alone, or by the insertion of a reinforced Silastic pouch or patch. The mortality rate has been reduced from 62% to 33% over the past 6 years. Despite better metabolic and respiratory care and intravenous alimentation, serious complications still occur, particularly when prematurity and associated anomalies such as atresia or meconium ileus exist. Other problems were respiratory complications, ileus, perforation, gangrene, intestinal obstruction, enterocolitis and disaccharide intolerance. The long-term follow-up of some of these patients is described."} {"id": "PMID:156405", "title": "[Clinical aspects of the anti-androgens].", "content": "The ongoing development and gradual availability of the new anti-androgens hold exciting clinical implications for the future. The biosynthesis and interchangeability of the sex steroids, the roles of the ovaries and adrenals and the value and interpretation of biochemical assays in clinical practice are briefly discussed. Because the anti-androgens are used primarily for seborrhoea/acne/hirsutism/oligomenorrhoea, the pathophysiological basis of this socially debilitating syndrome is discussed. The classification of the anti-androgens, their indications, side-effects, dosage schemes and results of treatment are reviewed. Finally, a summary of a possible clinical management regimen is presented.", "contents": "[Clinical aspects of the anti-androgens]. The ongoing development and gradual availability of the new anti-androgens hold exciting clinical implications for the future. The biosynthesis and interchangeability of the sex steroids, the roles of the ovaries and adrenals and the value and interpretation of biochemical assays in clinical practice are briefly discussed. Because the anti-androgens are used primarily for seborrhoea/acne/hirsutism/oligomenorrhoea, the pathophysiological basis of this socially debilitating syndrome is discussed. The classification of the anti-androgens, their indications, side-effects, dosage schemes and results of treatment are reviewed. Finally, a summary of a possible clinical management regimen is presented."} {"id": "PMID:156407", "title": "Laparoscopy for the general surgeon.", "content": "A group of three general surgeons in a small community hospital found laparoscopy and laparascopic tuball ligations to be a valuable addition to their practice. Equipment costs and training costs are not prohibitive for a small hospital. The procedures result in minimal morbidity, and have enhanced treatment of gynecologic problems.", "contents": "Laparoscopy for the general surgeon. A group of three general surgeons in a small community hospital found laparoscopy and laparascopic tuball ligations to be a valuable addition to their practice. Equipment costs and training costs are not prohibitive for a small hospital. The procedures result in minimal morbidity, and have enhanced treatment of gynecologic problems."} {"id": "PMID:156406", "title": "Evaluation of hysterectomized women seen at a clinic for treatment of sexually transmitted diseases.", "content": "Thirty-one women who had had total hysterectomies, seen in a venereal disease clinic, were interviewed and examined. Thirteen (31%) of the 31 women had acquired one or more venereal infections after hysterectomy. The diseases, listed in order of decreasing frequency, were trichomoniasis (four cases), gonorrhea (three), early latent syphilis (three), vaginal candidiasis (three), secondary syphilis (two), late latent syphilis (two), and condyloma acuminatum (one). These results indicate that clinicians working in venereal disease clinics must maintain as high an index of suspicion of sexually transmissible diseases for women with hysterectomies as for all other women.", "contents": "Evaluation of hysterectomized women seen at a clinic for treatment of sexually transmitted diseases. Thirty-one women who had had total hysterectomies, seen in a venereal disease clinic, were interviewed and examined. Thirteen (31%) of the 31 women had acquired one or more venereal infections after hysterectomy. The diseases, listed in order of decreasing frequency, were trichomoniasis (four cases), gonorrhea (three), early latent syphilis (three), vaginal candidiasis (three), secondary syphilis (two), late latent syphilis (two), and condyloma acuminatum (one). These results indicate that clinicians working in venereal disease clinics must maintain as high an index of suspicion of sexually transmissible diseases for women with hysterectomies as for all other women."} {"id": "PMID:156413", "title": "Prune belly syndrome and fetal ascites.", "content": "A case of prune belly syndrome (PBS) in a 22 week male fetus is described. All the features characteristic of the syndrome were present: absence of abdominal muscle; dilatation of the bladder, ureters, and renal pelves; and undescended testes. In addition, there was marked ascites. The rectus abdominis muscles were entirely absent whereas other abdominal muscles were only absent centrally. Between regions of normal and absent musculature muscle fibers were sparse, enlarged, frequently disrupted, and mostly in the myotubule stage. The prostate was thin-walled and its urethra greatly expanded. The testes lay close to the corresponding ureters and each ductus deferens was only partially present. It is considered that prostatic dysgenesis and fetal ascites are key factors in the causation of PBS.", "contents": "Prune belly syndrome and fetal ascites. A case of prune belly syndrome (PBS) in a 22 week male fetus is described. All the features characteristic of the syndrome were present: absence of abdominal muscle; dilatation of the bladder, ureters, and renal pelves; and undescended testes. In addition, there was marked ascites. The rectus abdominis muscles were entirely absent whereas other abdominal muscles were only absent centrally. Between regions of normal and absent musculature muscle fibers were sparse, enlarged, frequently disrupted, and mostly in the myotubule stage. The prostate was thin-walled and its urethra greatly expanded. The testes lay close to the corresponding ureters and each ductus deferens was only partially present. It is considered that prostatic dysgenesis and fetal ascites are key factors in the causation of PBS."} {"id": "PMID:156419", "title": "Transplantation in miniature swine. VI. Factors influencing survival of renal allografts.", "content": "Renal allografts were performed between and among animals from three herds of miniature swine that were selectively inbred to homozygosity at the major histocompatibility complex, MSLA. The results suggest several genetic factors which influence the survival of renal allografts in these animals. As expected, the major histocompatibility complex (MHC) was of dominant importance, and all MSLA-mismatched grafts were rejected promptly (12 +/- 3.7 days). Some MSLA-matched grafts were also rejected (30 +/- 15.0 days), indicating that non-MSLA loci also determine antigens which can lead to kidney rejection. Other MSLA-matched grafts were accepted indefinitely. At least one immune response gene that determined ability to reject kidneys across non-MSLA differences seemed to be segregating in our swine population. Animals that had accepted MSLA-matched renal grafts for extended periods demonstrated markedly prolonged survival of subsequent donor skin grafts compared to skin graft survival across the same non-MSLA difference in normal animals. This finding suggests that failure to reject kidneys across non-MSLA differences indicates systemic tolerance, and that there may be a relationship between the induction of such tolerance and the proposed immune response gene controlling rejection.", "contents": "Transplantation in miniature swine. VI. Factors influencing survival of renal allografts. Renal allografts were performed between and among animals from three herds of miniature swine that were selectively inbred to homozygosity at the major histocompatibility complex, MSLA. The results suggest several genetic factors which influence the survival of renal allografts in these animals. As expected, the major histocompatibility complex (MHC) was of dominant importance, and all MSLA-mismatched grafts were rejected promptly (12 +/- 3.7 days). Some MSLA-matched grafts were also rejected (30 +/- 15.0 days), indicating that non-MSLA loci also determine antigens which can lead to kidney rejection. Other MSLA-matched grafts were accepted indefinitely. At least one immune response gene that determined ability to reject kidneys across non-MSLA differences seemed to be segregating in our swine population. Animals that had accepted MSLA-matched renal grafts for extended periods demonstrated markedly prolonged survival of subsequent donor skin grafts compared to skin graft survival across the same non-MSLA difference in normal animals. This finding suggests that failure to reject kidneys across non-MSLA differences indicates systemic tolerance, and that there may be a relationship between the induction of such tolerance and the proposed immune response gene controlling rejection."} {"id": "PMID:156420", "title": "Transplantation in miniature swine. VII. Evidence for cellular immune mechanisms in hyperacute rejection of renal alografts.", "content": "Renal allografts were performed in miniature swine that were identical at their major histocompatibility locus and were presensitized by skin grafts from their prospective renal donors. All of these renal grafts were rejected in a hyperacute or markedly accelerated manner compared to the survival of comparable grafts in nonsensitized animals. Studies directed at the mechanism of this rejection revealed no circulating recipient antidonor antibodies by several serological assays. In contrast, mixed lymphocyte cultures (MLCs) and cell-mediated lympholysis (CML) assays demonstrated marked recipient antidonor lymphocyte reactivity that appeared after skin grafts, diminished during the tenure of the renal graft in the host circulation, and reappeared after removal of the rejected kidney. These results suggest that cellular immune mechanisms may plan a role in the accelerated rejection of major histocompatibility complex (MHC)-identical renal allografts.", "contents": "Transplantation in miniature swine. VII. Evidence for cellular immune mechanisms in hyperacute rejection of renal alografts. Renal allografts were performed in miniature swine that were identical at their major histocompatibility locus and were presensitized by skin grafts from their prospective renal donors. All of these renal grafts were rejected in a hyperacute or markedly accelerated manner compared to the survival of comparable grafts in nonsensitized animals. Studies directed at the mechanism of this rejection revealed no circulating recipient antidonor antibodies by several serological assays. In contrast, mixed lymphocyte cultures (MLCs) and cell-mediated lympholysis (CML) assays demonstrated marked recipient antidonor lymphocyte reactivity that appeared after skin grafts, diminished during the tenure of the renal graft in the host circulation, and reappeared after removal of the rejected kidney. These results suggest that cellular immune mechanisms may plan a role in the accelerated rejection of major histocompatibility complex (MHC)-identical renal allografts."} {"id": "PMID:156418", "title": "Removal of anticomplementary activity from human immune serum globulins by treatment with purified human plasmin.", "content": "Human immune serum globulin preparations were treated with highly purified human plasmin to remove their anticomplementary activity. The extent of anticomplementary activity removed and the amount of fragmentation obtained from immune serum globulin preparation depended upon the amount of plasmin added and the length of incubation time. The enzymatic reaction was stopped by removing plasmin with bentonite adsorption. Two types of plasmin-treated immune serum globulin that may be used for intravenous injection were obtained. One was a more fragmented product (35 to 45%) with lower anticomplementary activity, the other was a less degraded product (15 to 20%) with slightly higher anticomplementary activity. Antibody content of the former preparation was somewhat reduced while that of the latter preparation was virtually unchanged from the untreated immune serum globulin.", "contents": "Removal of anticomplementary activity from human immune serum globulins by treatment with purified human plasmin. Human immune serum globulin preparations were treated with highly purified human plasmin to remove their anticomplementary activity. The extent of anticomplementary activity removed and the amount of fragmentation obtained from immune serum globulin preparation depended upon the amount of plasmin added and the length of incubation time. The enzymatic reaction was stopped by removing plasmin with bentonite adsorption. Two types of plasmin-treated immune serum globulin that may be used for intravenous injection were obtained. One was a more fragmented product (35 to 45%) with lower anticomplementary activity, the other was a less degraded product (15 to 20%) with slightly higher anticomplementary activity. Antibody content of the former preparation was somewhat reduced while that of the latter preparation was virtually unchanged from the untreated immune serum globulin."} {"id": "PMID:156444", "title": "Delayed extrusion of testicular prosthesis.", "content": "A case of migration and extrusion of a testicular prosthesis with erosion of the fixation tab through the skin is reported. Predisposing factors are discussed. Trimming the corners of the tab prior to fixation is recommended as well as anchoring it firmly to the most dependent portion of the scrotum, using nonabsorbable sutures.", "contents": "Delayed extrusion of testicular prosthesis. A case of migration and extrusion of a testicular prosthesis with erosion of the fixation tab through the skin is reported. Predisposing factors are discussed. Trimming the corners of the tab prior to fixation is recommended as well as anchoring it firmly to the most dependent portion of the scrotum, using nonabsorbable sutures."} {"id": "PMID:156445", "title": "[Surgical tactics in postoperative eventration in children].", "content": "As a result of a clinical analysis of 66 observations on eventrations in children, the surgical tactics in this condition is founded. 38 experiments on dogs have shown that the maximal disorders of protein metabolism and transport occur on the 6th to 12th days, that is during the period of formation and maturation of the connective scar. On the grounds of the obtained findings the authors suggest to use wider albumins, plasma and erithrocytic mass for weak patients in preoperative and postoperative management.", "contents": "[Surgical tactics in postoperative eventration in children]. As a result of a clinical analysis of 66 observations on eventrations in children, the surgical tactics in this condition is founded. 38 experiments on dogs have shown that the maximal disorders of protein metabolism and transport occur on the 6th to 12th days, that is during the period of formation and maturation of the connective scar. On the grounds of the obtained findings the authors suggest to use wider albumins, plasma and erithrocytic mass for weak patients in preoperative and postoperative management."} {"id": "PMID:156446", "title": "Back muscle necrosis of pigs.", "content": "The clinical signs and pathological features of back muscle necrosis (BMN) in four pigs from three English pig herds were similar to those recorded in pigs from mainland Europe. The observations made support the view that BMN is a special manifestation of the porcine stress syndrome. Diagnosis of acute BMN can be made clinically supported by the analysis of plasma creatine phosphokinase activity and can be confirmed post mortem by macroscopic and microscopic observation on the back muscles.", "contents": "Back muscle necrosis of pigs. The clinical signs and pathological features of back muscle necrosis (BMN) in four pigs from three English pig herds were similar to those recorded in pigs from mainland Europe. The observations made support the view that BMN is a special manifestation of the porcine stress syndrome. Diagnosis of acute BMN can be made clinically supported by the analysis of plasma creatine phosphokinase activity and can be confirmed post mortem by macroscopic and microscopic observation on the back muscles."} {"id": "PMID:156442", "title": "[Molecular organization of Mg2+, Ca2+-ATPase of sarcoplasmic reticulum].", "content": "The article deals with the results of studies on the structure and properties of discrete sites in a molecule of sarcoplasmic reticulum Mg2+, Ca2+-ATPase obtained during its fragmentation in the process of its limited hydrolysis by trypsin. It is established to contain three fragments with the molecular mass of 45 000, 30 000 and 20 000 Daltons. Some properties of these fragments are determined by the amino acid analysis, inhibitory analysis with application of radiactive labels and also of immunochemical analysis. The properties show that the first fragment is hydrophobic and the others are hydrophilic; these properties show that the first fragment is hydrophobic and the others are hydrophilic; these properties determine the location of the fragments in the sarcoplasmic reticulum membrane. The fragment with the molecular mass of 45 000 Daltons forms in it a nonspecific channel as if \"sewing\" it, two other fragments of the Mg2+, Ca2+-ATPase are located at the outer side of the membrane, the fragment with the molecular weight of 20 000 occupying a middle position between the fragments with molecular weight of 45 000 and 30 000, thus creating a selective respect to calcium \"valve\" to the nonspecific channel. This discrete part of Mg2+, Ca2+-ATPase possesses the ionophoric activity. The fragment with molecular weight of 30 000 is the energy converter. The site hydrolyzing AMP is located in it. The models (hypothetic) are presented for the Ca2+ active transpprt through biological membranes with Mg2+, Ca2+-ATPase participation.", "contents": "[Molecular organization of Mg2+, Ca2+-ATPase of sarcoplasmic reticulum]. The article deals with the results of studies on the structure and properties of discrete sites in a molecule of sarcoplasmic reticulum Mg2+, Ca2+-ATPase obtained during its fragmentation in the process of its limited hydrolysis by trypsin. It is established to contain three fragments with the molecular mass of 45 000, 30 000 and 20 000 Daltons. Some properties of these fragments are determined by the amino acid analysis, inhibitory analysis with application of radiactive labels and also of immunochemical analysis. The properties show that the first fragment is hydrophobic and the others are hydrophilic; these properties show that the first fragment is hydrophobic and the others are hydrophilic; these properties determine the location of the fragments in the sarcoplasmic reticulum membrane. The fragment with the molecular mass of 45 000 Daltons forms in it a nonspecific channel as if \"sewing\" it, two other fragments of the Mg2+, Ca2+-ATPase are located at the outer side of the membrane, the fragment with the molecular weight of 20 000 occupying a middle position between the fragments with molecular weight of 45 000 and 30 000, thus creating a selective respect to calcium \"valve\" to the nonspecific channel. This discrete part of Mg2+, Ca2+-ATPase possesses the ionophoric activity. The fragment with molecular weight of 30 000 is the energy converter. The site hydrolyzing AMP is located in it. The models (hypothetic) are presented for the Ca2+ active transpprt through biological membranes with Mg2+, Ca2+-ATPase participation."} {"id": "PMID:156462", "title": "[Characteristics of human plasminogen activator and of a fraction of fibrinolytically active plasma enriched with this enzyme].", "content": "An activator of plasminogen with specific activity 203 AU/mg was isolated from blood plasma with fibrinolytic activity, obtained from blood of suddenly decreased patients. Specific activity of the plasminogen activator exceeded 88-fold the activity of the initial blood plasma. The protein was identified with a glycoprotein, similar to beta-globulin; its molecular weight was 70,000 as shown by gel filtration; the isoelectric point was at pH 6.2. The plasminogen activator remained stable after heating up to 50 degrees. Effects of pH in an incubation media and of cations on the activity of the plasminogen activator were studied. A fraction containing the fibrinolytic activity and enriched with plasminogen activator was obtained from the blood plasma after fractionation at low temperature with ethanol at definite pH value. The specific fibrinolytic activity in the fraction exceeded 17.6-fold the activity of blood plasma. The fraction exhibited high thrombolytic and antithrombin activities in vitro. It was similar to streptase and streptokinase preparations in its throm-bolytic effect. Relative species specificity was found in studies of the fibrinolytic and antithrombin effects of the fraction containing fibrinolytic activity.", "contents": "[Characteristics of human plasminogen activator and of a fraction of fibrinolytically active plasma enriched with this enzyme]. An activator of plasminogen with specific activity 203 AU/mg was isolated from blood plasma with fibrinolytic activity, obtained from blood of suddenly decreased patients. Specific activity of the plasminogen activator exceeded 88-fold the activity of the initial blood plasma. The protein was identified with a glycoprotein, similar to beta-globulin; its molecular weight was 70,000 as shown by gel filtration; the isoelectric point was at pH 6.2. The plasminogen activator remained stable after heating up to 50 degrees. Effects of pH in an incubation media and of cations on the activity of the plasminogen activator were studied. A fraction containing the fibrinolytic activity and enriched with plasminogen activator was obtained from the blood plasma after fractionation at low temperature with ethanol at definite pH value. The specific fibrinolytic activity in the fraction exceeded 17.6-fold the activity of blood plasma. The fraction exhibited high thrombolytic and antithrombin activities in vitro. It was similar to streptase and streptokinase preparations in its throm-bolytic effect. Relative species specificity was found in studies of the fibrinolytic and antithrombin effects of the fraction containing fibrinolytic activity."} {"id": "PMID:156467", "title": "[Structural investigations on lipopolysaccharides of mutants S SF 1111 and R 595 SF 1167 of Salmonella minnesota (author's transl)].", "content": "The lipolysaccharides of two mutants of Salmonella minnesota with known chemical structure were investigated by X-ray methods. Both thickness of the lipopolysaccharide layer and arrangement of the molecular components could be estimated. Using these informations a space-filling model of the structure was built.", "contents": "[Structural investigations on lipopolysaccharides of mutants S SF 1111 and R 595 SF 1167 of Salmonella minnesota (author's transl)]. The lipolysaccharides of two mutants of Salmonella minnesota with known chemical structure were investigated by X-ray methods. Both thickness of the lipopolysaccharide layer and arrangement of the molecular components could be estimated. Using these informations a space-filling model of the structure was built."} {"id": "PMID:156468", "title": "On the dynamic model of tRNA: recent experimental findings.", "content": "Recent experimental findings are shown to support various aspects of the dynamic model of tRNA proposed earlier and the interaction between tRNA, mRNA and the ribosomal RNA's. Extra loop of tRNA molecule is suggested to play a role in recognizing the corresponding amino acids and a correlation is presented between the tRNA molecules and the corresponding amino acids as tabulated by the genetic tableau.", "contents": "On the dynamic model of tRNA: recent experimental findings. Recent experimental findings are shown to support various aspects of the dynamic model of tRNA proposed earlier and the interaction between tRNA, mRNA and the ribosomal RNA's. Extra loop of tRNA molecule is suggested to play a role in recognizing the corresponding amino acids and a correlation is presented between the tRNA molecules and the corresponding amino acids as tabulated by the genetic tableau."} {"id": "PMID:156471", "title": "Electron microscopy of synaptonemal complexes in semithin sections.", "content": "The technique of osmium tetroxide fixation followed by a treatment with p-phenylenediamine was applied to mouse testes in order to analyze pachytene nuclei. Observation of Epon semithin sections (0.25--0.5 micrometer) in conventional electron microscopy revealed the presence of positively stained synaptonemal complexes surrounded by unstained chromatin. The present results show that by using this method a suitable contrast and resolution can be achieved for semithin sections, which facilitates the topographical study of synaptonemal complexes.", "contents": "Electron microscopy of synaptonemal complexes in semithin sections. The technique of osmium tetroxide fixation followed by a treatment with p-phenylenediamine was applied to mouse testes in order to analyze pachytene nuclei. Observation of Epon semithin sections (0.25--0.5 micrometer) in conventional electron microscopy revealed the presence of positively stained synaptonemal complexes surrounded by unstained chromatin. The present results show that by using this method a suitable contrast and resolution can be achieved for semithin sections, which facilitates the topographical study of synaptonemal complexes."} {"id": "PMID:156472", "title": "A new mutant affecting aldehyde oxidase in Drosophila melanogaster.", "content": "A new locus, Aldox-2, which affects the activity and heat stability of aldehyde oxidase in D. melanogaster is described. The Aldox-2 locus is localized to map position 86 on chromosome 2, between c and px. Aldehyde oxidase activity in aldox-2 homozygotes is approximately 25--30% that of the Oregon-R wild-type control strain. The enzyme from the mutant stock is much more heat labile than is the enzyme from the wild-type strain. Both the activity and heat phenotypes are completely recessive.", "contents": "A new mutant affecting aldehyde oxidase in Drosophila melanogaster. A new locus, Aldox-2, which affects the activity and heat stability of aldehyde oxidase in D. melanogaster is described. The Aldox-2 locus is localized to map position 86 on chromosome 2, between c and px. Aldehyde oxidase activity in aldox-2 homozygotes is approximately 25--30% that of the Oregon-R wild-type control strain. The enzyme from the mutant stock is much more heat labile than is the enzyme from the wild-type strain. Both the activity and heat phenotypes are completely recessive."} {"id": "PMID:156469", "title": "The molecular weight of rRNA precursor molecules and their processing in higher plant cells.", "content": "Actively dividing callus cells of higher plants (Petroselinum crispum, Daucus carota, Acer pseudoplatanus) were used to detect the primary gene product of rDNA in vivo. Parsley and carrot cells were labelled with [32P]orthophosphate. Under non-denaturing conditions, in both cases only one high molecular weight rRNA precursor was present on polyacrylamide gels. Its molecular weight did not exceed 2.5 x 10(6) dalton. Under denaturing conditions, 2.0--2.1 x 10(6) dalton were determined on formamide gels. This rRNA precursor was already present after a labelling period of 5--10 min. In parsley cells labelled mature rRNA (25S and 18S) arrived in the cytoplasm 45 min after onset of incubation. In Acer pseudoplatanus incubated with [3H]uridine two rapidly labelled components did emerge from polyacrylamide gels without formamide; their molecular weights were 2.3 and 3.2--3.4 x 10(6) dalton. After electrophoresis in formamide, the larger component disappeared, thus indicating that it would be an intermolecular aggregate of different RNAs. From these results we have no evidence for the existence of rRNA precursors exceeding the molecular weight of 2.5 x 10(6) dalton.", "contents": "The molecular weight of rRNA precursor molecules and their processing in higher plant cells. Actively dividing callus cells of higher plants (Petroselinum crispum, Daucus carota, Acer pseudoplatanus) were used to detect the primary gene product of rDNA in vivo. Parsley and carrot cells were labelled with [32P]orthophosphate. Under non-denaturing conditions, in both cases only one high molecular weight rRNA precursor was present on polyacrylamide gels. Its molecular weight did not exceed 2.5 x 10(6) dalton. Under denaturing conditions, 2.0--2.1 x 10(6) dalton were determined on formamide gels. This rRNA precursor was already present after a labelling period of 5--10 min. In parsley cells labelled mature rRNA (25S and 18S) arrived in the cytoplasm 45 min after onset of incubation. In Acer pseudoplatanus incubated with [3H]uridine two rapidly labelled components did emerge from polyacrylamide gels without formamide; their molecular weights were 2.3 and 3.2--3.4 x 10(6) dalton. After electrophoresis in formamide, the larger component disappeared, thus indicating that it would be an intermolecular aggregate of different RNAs. From these results we have no evidence for the existence of rRNA precursors exceeding the molecular weight of 2.5 x 10(6) dalton."} {"id": "PMID:156473", "title": "[The inbred mouse strain STU. Development and properties (author's transl)].", "content": "The highly inbred STU mouse strain (up to 100 inbred generations) was developed from a German white mouse colony. Its properties are described with special emphasis on the occurrence of tumors, occurrence of C-type oncornaviruses and on its immunological reactivity. The predominant tumor is a fibrosarcoma (approximately 23% incidence).", "contents": "[The inbred mouse strain STU. Development and properties (author's transl)]. The highly inbred STU mouse strain (up to 100 inbred generations) was developed from a German white mouse colony. Its properties are described with special emphasis on the occurrence of tumors, occurrence of C-type oncornaviruses and on its immunological reactivity. The predominant tumor is a fibrosarcoma (approximately 23% incidence)."} {"id": "PMID:156481", "title": "[Q fever in the Mordvinian ASSR].", "content": "In the serological (CFT) examination of patients with elevated temperature for Q fever positive results were obtained in 8.2--14% of cases. The number of positive results of the CFT in rural districts was higher (16%) than in urban districts (10.2%). A considerable percentage of positive results was observed among the workers of a meat-packing plant (25%) and among persons who regularly received milk at their work as a special diet (25--39.2%). In the Mordovian ASSR the infection seemed to be transmitted mainly by the alimentary and contact ways.", "contents": "[Q fever in the Mordvinian ASSR]. In the serological (CFT) examination of patients with elevated temperature for Q fever positive results were obtained in 8.2--14% of cases. The number of positive results of the CFT in rural districts was higher (16%) than in urban districts (10.2%). A considerable percentage of positive results was observed among the workers of a meat-packing plant (25%) and among persons who regularly received milk at their work as a special diet (25--39.2%). In the Mordovian ASSR the infection seemed to be transmitted mainly by the alimentary and contact ways."} {"id": "PMID:156482", "title": "[Social and work rehabilitation of schizophrenics under the shop conditions of an industrial enterprise].", "content": "The paper is concerned with the results and effectivity of rehabilitation of 219 schizophrenic patients with unfavourable variants of development, who worked for 1--3 years in shops of an enterprise, intended for promoting the rehabilitative treatment and employment of mental patients. with the use of special rating scales, the efficacy of rehabilitation attained in therapeutic-occupational shops (TOS) and in industrial shops. The study demonstrated that the results of rehabilitation in conditions of a shop are significantly higher than the corresponding indices in conditions of TOS.", "contents": "[Social and work rehabilitation of schizophrenics under the shop conditions of an industrial enterprise]. The paper is concerned with the results and effectivity of rehabilitation of 219 schizophrenic patients with unfavourable variants of development, who worked for 1--3 years in shops of an enterprise, intended for promoting the rehabilitative treatment and employment of mental patients. with the use of special rating scales, the efficacy of rehabilitation attained in therapeutic-occupational shops (TOS) and in industrial shops. The study demonstrated that the results of rehabilitation in conditions of a shop are significantly higher than the corresponding indices in conditions of TOS."} {"id": "PMID:156483", "title": "The fine structure of denervated and reinnervated muscle spindles: morphometric study of intrafusal muscle fibers.", "content": "The fine structure of normal, denervated, and reinnervated muscle spindles in lower lumbrical muscles of rats was studied morphometrically at time intervals ranging from 3-14 months. In control spindles, the mean transverse area of mitochondria was estimated to be more than twice as large in nuclear chain than in typical nuclear bag fibers. Following denervation, there was a severe decrease of the mean number and transverse area of mitochondria, and a moderate, but statistically significant decrease of the mean transverse area of intrafusal muscle fibers (IMFs) despite an increase of the number of IMFs. At 12-14 months of reinnervation, changes of the transverse areas of IMFs were statistically insignificant, but the mean values for the mitochondria were incompletely restored. At 4 x 3 months, after fourfold repeated crush injuries to the nerve, most of the values estimated (transverse area of mitochondria; number, shape, and transverse area of IMFs and nuclei) tended to approach those in denervated rather than in reinnervated IMFs. The differences of the reactions of intra- and extrafusal muscle fibers following complete motor and sensory denervation appeared to be in accordance with their normal dimensional dissimilarities.", "contents": "The fine structure of denervated and reinnervated muscle spindles: morphometric study of intrafusal muscle fibers. The fine structure of normal, denervated, and reinnervated muscle spindles in lower lumbrical muscles of rats was studied morphometrically at time intervals ranging from 3-14 months. In control spindles, the mean transverse area of mitochondria was estimated to be more than twice as large in nuclear chain than in typical nuclear bag fibers. Following denervation, there was a severe decrease of the mean number and transverse area of mitochondria, and a moderate, but statistically significant decrease of the mean transverse area of intrafusal muscle fibers (IMFs) despite an increase of the number of IMFs. At 12-14 months of reinnervation, changes of the transverse areas of IMFs were statistically insignificant, but the mean values for the mitochondria were incompletely restored. At 4 x 3 months, after fourfold repeated crush injuries to the nerve, most of the values estimated (transverse area of mitochondria; number, shape, and transverse area of IMFs and nuclei) tended to approach those in denervated rather than in reinnervated IMFs. The differences of the reactions of intra- and extrafusal muscle fibers following complete motor and sensory denervation appeared to be in accordance with their normal dimensional dissimilarities."} {"id": "PMID:156484", "title": "Serum levels of total dehydroepiandrosterone and total estrone in postmenopausal women with special regard to carcinoma of the uterine corpus.", "content": "Serum levels of total dehydroepiandrosterone and total estrone were determined in 18 postmenopausal women with carcinoma of the uterine corpus (stage I, grade 1-3) and in 40 healthy postmenopausal women. Elevated levels of both steroids were found in the carcinoma group, for dehydroepiandrosterone 2010+/-195 vs. 1299+/-117 nM, p less than 0.01, and for estrone 2,38+/-0.24 vs. 1.36+/-0.11 nM, p less than 0.001. Dehydroepiandrosterone as well as the precursors of estrone are almost exclusively of adrenal origin in the postmenopausal woman. Thus these findings indicate a role of the adrenal cortex in the etiology of corpus carcinoma, either by providing increased levels of substrate for the peripheral synthesis of estrone or a direct action of adrenal androgens on the endometrial tissue.", "contents": "Serum levels of total dehydroepiandrosterone and total estrone in postmenopausal women with special regard to carcinoma of the uterine corpus. Serum levels of total dehydroepiandrosterone and total estrone were determined in 18 postmenopausal women with carcinoma of the uterine corpus (stage I, grade 1-3) and in 40 healthy postmenopausal women. Elevated levels of both steroids were found in the carcinoma group, for dehydroepiandrosterone 2010+/-195 vs. 1299+/-117 nM, p less than 0.01, and for estrone 2,38+/-0.24 vs. 1.36+/-0.11 nM, p less than 0.001. Dehydroepiandrosterone as well as the precursors of estrone are almost exclusively of adrenal origin in the postmenopausal woman. Thus these findings indicate a role of the adrenal cortex in the etiology of corpus carcinoma, either by providing increased levels of substrate for the peripheral synthesis of estrone or a direct action of adrenal androgens on the endometrial tissue."} {"id": "PMID:156485", "title": "Kartagener's syndrome--a reappraisal.", "content": "Congenital lack of dynein arms in cilia has recently been associated with Kartagener's syndrome. Ultrastructural findings from six patients with chronic stagnant secretion in the respiratory tract are briefly reported. Only one of the patients had the complete syndrome. The term Immotile-cilia syndrome has been coined, and it is suggested that Kartagener's syndrome should be included in this entity.", "contents": "Kartagener's syndrome--a reappraisal. Congenital lack of dynein arms in cilia has recently been associated with Kartagener's syndrome. Ultrastructural findings from six patients with chronic stagnant secretion in the respiratory tract are briefly reported. Only one of the patients had the complete syndrome. The term Immotile-cilia syndrome has been coined, and it is suggested that Kartagener's syndrome should be included in this entity."} {"id": "PMID:156487", "title": "Effect of splenic nerve stimulation on the contents of noradrenaline, ATP and sulphomucopolysaccharides in noradrenergic vesicle fractions from the cat spleen.", "content": "In order to assess the effect of splenic nerve stimulation on the contents of noradrenaline, ATP and 35S-labelled compounds in noradrenergic vesicles from the spleen, experiments were carried out on the cat spleen in situ, its frontal portion being used as control. Particulate fractions containing noradrenergic vesicles were isolated on Ficoll gradient centrifugation of homogenates from both portions of the spleen. The cats received phenoxybenzamine (10 mg/kg) and imipramine (5 mg/kg) to inhibit the contractive response of the spleen to nerve stimulation and the reuptake of noradrenaline (NA) into nerve terminals. Administration of the drugs did not significantly affect the levels of NA, ATP and 35S (presumably in sulphomucopolysaccarides, SMPSs). In response to prolonged stimulation of the splenic nerve a significant loss of NA from noradrenergic vesicles occurred, whereas levels of ATP and 35S-labelled compounds remained unchanged. The results indicate that a discharge of NA in response to nerve stimulation is not accompanied by simultaneous discharge of ATP and SMPSs.", "contents": "Effect of splenic nerve stimulation on the contents of noradrenaline, ATP and sulphomucopolysaccharides in noradrenergic vesicle fractions from the cat spleen. In order to assess the effect of splenic nerve stimulation on the contents of noradrenaline, ATP and 35S-labelled compounds in noradrenergic vesicles from the spleen, experiments were carried out on the cat spleen in situ, its frontal portion being used as control. Particulate fractions containing noradrenergic vesicles were isolated on Ficoll gradient centrifugation of homogenates from both portions of the spleen. The cats received phenoxybenzamine (10 mg/kg) and imipramine (5 mg/kg) to inhibit the contractive response of the spleen to nerve stimulation and the reuptake of noradrenaline (NA) into nerve terminals. Administration of the drugs did not significantly affect the levels of NA, ATP and 35S (presumably in sulphomucopolysaccarides, SMPSs). In response to prolonged stimulation of the splenic nerve a significant loss of NA from noradrenergic vesicles occurred, whereas levels of ATP and 35S-labelled compounds remained unchanged. The results indicate that a discharge of NA in response to nerve stimulation is not accompanied by simultaneous discharge of ATP and SMPSs."} {"id": "PMID:156488", "title": "Massive congenital tricuspid insufficiency in the newborn.", "content": "Three cases of massive congenital tricuspid incompetence in the newborn are reported and discussed from diagnostic, pathologic and etiologic points of view. The diagnosis is important as cases have been reported with spontaneous resolution.", "contents": "Massive congenital tricuspid insufficiency in the newborn. Three cases of massive congenital tricuspid incompetence in the newborn are reported and discussed from diagnostic, pathologic and etiologic points of view. The diagnosis is important as cases have been reported with spontaneous resolution."} {"id": "PMID:156489", "title": "Incarcerated Spigelian hernia: ultrasonic differential diagnosis.", "content": "The gray scale ultrasonic findings in a case of incarcerated Spigelian hernia are presented. This hernia is uncommon, and the clinical diagnosis can be difficult. The appearance of the lesion is compared with others in and about the abdominal wall, including rectus sheath hematoma, seroma, abscess, peritoneal tumor implants, and pseudocyst at the end of a ventriculoperitoneal shunt. Clinical and sonographic differentiation is emphasized.", "contents": "Incarcerated Spigelian hernia: ultrasonic differential diagnosis. The gray scale ultrasonic findings in a case of incarcerated Spigelian hernia are presented. This hernia is uncommon, and the clinical diagnosis can be difficult. The appearance of the lesion is compared with others in and about the abdominal wall, including rectus sheath hematoma, seroma, abscess, peritoneal tumor implants, and pseudocyst at the end of a ventriculoperitoneal shunt. Clinical and sonographic differentiation is emphasized."} {"id": "PMID:156492", "title": "Complete occlusion of the left main coronary artery.", "content": "In this report, we describe the clinical, hemodynamic, and angiographic findings in three patients with atherosclerotic complete occlusion of the left main coronary artery. This rare entity was only seen in three out of 7,000 coronary angiograms. The three patients had extensive right-to-left collateralization. Two patients underwent saphenous vein bypass surgery and are asymptomatic, while the third patient died awaiting surgery. We suggest that patients with complete left main occlusion must undergo surgery as soon as possible.", "contents": "Complete occlusion of the left main coronary artery. In this report, we describe the clinical, hemodynamic, and angiographic findings in three patients with atherosclerotic complete occlusion of the left main coronary artery. This rare entity was only seen in three out of 7,000 coronary angiograms. The three patients had extensive right-to-left collateralization. Two patients underwent saphenous vein bypass surgery and are asymptomatic, while the third patient died awaiting surgery. We suggest that patients with complete left main occlusion must undergo surgery as soon as possible."} {"id": "PMID:156493", "title": "Noninvasive evaluation of the athletic heart: sprinters versus endurance runners.", "content": "To evaluate possible differences in the cardiac effects of different types of running training, 22 competing male runners--10 sprinters and 12 endurance runners--were studied with a physical examination, electrocardiography, chest X-ray film and echocardiography. Thirteen sedentary men served as control subjects. There were no differences between the athletic groups in physical findings. However, left ventricular hypertrophy in the electrocardiogram was more apparent in the endurance runners (P less than 0.05), whose relative heart size on chest X-ray examination was also greater than in the sprinters (P less than 0.02). On echocardiography the left ventricular end-diastolic volume was equally greater than normal in both groups of athletes (P less than 0.005), but in the endurance runners the percent chance of the minor axis diameter in systole was greater than in the sprinters or control subjects (P less than 0.02). Values for left ventricular wall thickness and mass were greater than normal in both groups of athletes but were higher in the endurance runners than in the sprinters (P less than 0.001). The left atrial diameter was apparently greater in the endurance runners than in the sprinters or control subjects (P less than 0.001), whereas that of the sprinters did not differ from normal. Thus, intensive sprinter training seems to dilate the left ventricle but causes less increase in wall thickness and mass than training for endurance running and no change in left ventricular function or left atrial size. Endurance running causes left ventricular dilatation equal to that of sprinter training, greater wall hypertrophy and improved systolic emptying of the left ventricle, and it also dilates the left atrium perhaps because of decreased left ventricular compliance.", "contents": "Noninvasive evaluation of the athletic heart: sprinters versus endurance runners. To evaluate possible differences in the cardiac effects of different types of running training, 22 competing male runners--10 sprinters and 12 endurance runners--were studied with a physical examination, electrocardiography, chest X-ray film and echocardiography. Thirteen sedentary men served as control subjects. There were no differences between the athletic groups in physical findings. However, left ventricular hypertrophy in the electrocardiogram was more apparent in the endurance runners (P less than 0.05), whose relative heart size on chest X-ray examination was also greater than in the sprinters (P less than 0.02). On echocardiography the left ventricular end-diastolic volume was equally greater than normal in both groups of athletes (P less than 0.005), but in the endurance runners the percent chance of the minor axis diameter in systole was greater than in the sprinters or control subjects (P less than 0.02). Values for left ventricular wall thickness and mass were greater than normal in both groups of athletes but were higher in the endurance runners than in the sprinters (P less than 0.001). The left atrial diameter was apparently greater in the endurance runners than in the sprinters or control subjects (P less than 0.001), whereas that of the sprinters did not differ from normal. Thus, intensive sprinter training seems to dilate the left ventricle but causes less increase in wall thickness and mass than training for endurance running and no change in left ventricular function or left atrial size. Endurance running causes left ventricular dilatation equal to that of sprinter training, greater wall hypertrophy and improved systolic emptying of the left ventricle, and it also dilates the left atrium perhaps because of decreased left ventricular compliance."} {"id": "PMID:156494", "title": "Abnormal cellular immune responses during acquired zinc deficiency.", "content": "The cellular immune response of a 17-year-old decerebrate male with acquired zinc deficiency was studied. He had been fed a commercial formula which contained 7.6 mg zinc per kilogram. His caloric intake had been inadequate as judged by his cachexia. A detailed pretreatment nutritional assessment (five separate observations) which included total serum protein and globulins, albumin, folate, vitamins A, B2, C, ceruloplasmin, and plasma zinc, copper, iron, and total iron binding capacity revealed that the patient was deficient only in zinc and calories. His plasma zinc was 41 +/- 5 microgram/d1 compared with our laboratory norm of 89 +/- 9 microgram/d1 for young adult males. Cellular immunity was assessed by delayed skin reactivity to dinitrochlorobenzene and by in vitro lymphocyte transformation studies. Before zinc therapy the patient rendered a negative skin reaction to dinitrochlorobenzene, and the ability of his lymphocytes to undergo blast transformation in response to mitogen stimulation was significantly depressed with a stimulation index of 4.7 +/- 0.8 as compared with 139.1 +/- 77.3 for controls. Within 3 weeks after zinc therapy (22.7 mg zinc per day) he demonstrated a positive delayed skin reaction to dinitrochlorobenzene and a normal lymphocyte response stimulation index = 205.5 +/- 42.6 versus 199.3 +/- 58.2 for control). In addition, a pretreatment facial seborrhea and a decubitus ulcer rapidly healed.", "contents": "Abnormal cellular immune responses during acquired zinc deficiency. The cellular immune response of a 17-year-old decerebrate male with acquired zinc deficiency was studied. He had been fed a commercial formula which contained 7.6 mg zinc per kilogram. His caloric intake had been inadequate as judged by his cachexia. A detailed pretreatment nutritional assessment (five separate observations) which included total serum protein and globulins, albumin, folate, vitamins A, B2, C, ceruloplasmin, and plasma zinc, copper, iron, and total iron binding capacity revealed that the patient was deficient only in zinc and calories. His plasma zinc was 41 +/- 5 microgram/d1 compared with our laboratory norm of 89 +/- 9 microgram/d1 for young adult males. Cellular immunity was assessed by delayed skin reactivity to dinitrochlorobenzene and by in vitro lymphocyte transformation studies. Before zinc therapy the patient rendered a negative skin reaction to dinitrochlorobenzene, and the ability of his lymphocytes to undergo blast transformation in response to mitogen stimulation was significantly depressed with a stimulation index of 4.7 +/- 0.8 as compared with 139.1 +/- 77.3 for controls. Within 3 weeks after zinc therapy (22.7 mg zinc per day) he demonstrated a positive delayed skin reaction to dinitrochlorobenzene and a normal lymphocyte response stimulation index = 205.5 +/- 42.6 versus 199.3 +/- 58.2 for control). In addition, a pretreatment facial seborrhea and a decubitus ulcer rapidly healed."} {"id": "PMID:156495", "title": "A method for cloning T-lymphocytic precursors in agar.", "content": "A new technique for the culture of T-lymphocytic colonies is reported. The method may be regarded as a human lymphocyte precursor cell assay, as is the myeloid colony culture for granulocyte-macrophage progenitors. The colonies arise under the simultaneous stimulation of phytohemagglutin and a leukocyte feeder. A linear relationship is found between colony numbers and cell numbers plated. The colonies represent aggregates of lymphoblast-like cells, the majority of which are capable of E-rosette formation, are responsive in mixed lymphocyte cultures, and do not exhibit surface immunoglobulins. Their density distribution profile is very similar to that of myeloid colony-forming cells. The finding that most of these colony-forming cells are recovered in the so-called lymphocyte-free stem cell fraction following density fractionation suggests that they originate from a lymphocytic precursor.", "contents": "A method for cloning T-lymphocytic precursors in agar. A new technique for the culture of T-lymphocytic colonies is reported. The method may be regarded as a human lymphocyte precursor cell assay, as is the myeloid colony culture for granulocyte-macrophage progenitors. The colonies arise under the simultaneous stimulation of phytohemagglutin and a leukocyte feeder. A linear relationship is found between colony numbers and cell numbers plated. The colonies represent aggregates of lymphoblast-like cells, the majority of which are capable of E-rosette formation, are responsive in mixed lymphocyte cultures, and do not exhibit surface immunoglobulins. Their density distribution profile is very similar to that of myeloid colony-forming cells. The finding that most of these colony-forming cells are recovered in the so-called lymphocyte-free stem cell fraction following density fractionation suggests that they originate from a lymphocytic precursor."} {"id": "PMID:156498", "title": "The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Beh\u00e7et's disease.", "content": "A kidney and lung biopsy were performed on a patient with active Beh\u00e7et's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Beh\u00e7et's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition.", "contents": "The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Beh\u00e7et's disease. A kidney and lung biopsy were performed on a patient with active Beh\u00e7et's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Beh\u00e7et's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition."} {"id": "PMID:156499", "title": "Calcification of the mitral annulus: etiology, clinical associations, complications and therapy.", "content": "This report reviews the clinical features of 80 patients with roentgenographically proved mitral annular calcification. The mean age of the group was 73 years, and there was a 2.5 to 1 female to male ratio. Evaluation for underlying cardiovascular disease revealed six patients with severe calcific valvular aortic stenosis; five patients with hypertrophic cardiomyopathy, 11 with mitral prolapse and 33 with significant arterial hypertension (blood pressure greater or equal to 150/96 mm Hg). Eighty-five per cent of the group (68 of 80 patients) had an underlying cardiac disorder associated with either chronically increased left ventricular systolic pressure or abnormal leaflet motion. Other cardiovascular abnormalities occurring as complications secondary to the mitral ring calcification included subacute bacterial endocarditis (three cases), arterial emboli (five episodes) and high grade atrioventricular block (16 cases). Twelve patients had severe mitral regurgitation; successful mitral valve replacement was carried out in four patients (all with myxomatous mitral tissue). Evidence of diffuse conduction system disease, not limited to the area of the cardiac fibrous skeleton, was found frequently (44 patients). Nine patients had sinus node dysfunction and 35 patients had electrocardiographic evidence of distal intraventricular (fascicular) block. Twenty-one patients eventually required pacemakers for management of symptomatic bradyarrhythmias. Atrial fibrillation was present in 23 patients. In this review it was found that calcification of the mitral annulus is frequently associated with or induces serious cardiovascular disease. Since some of these disorders may be modified by appropriate therapy, calcification of the mitral annulus should no longer be ignored as a benign marker of the elderly heart.", "contents": "Calcification of the mitral annulus: etiology, clinical associations, complications and therapy. This report reviews the clinical features of 80 patients with roentgenographically proved mitral annular calcification. The mean age of the group was 73 years, and there was a 2.5 to 1 female to male ratio. Evaluation for underlying cardiovascular disease revealed six patients with severe calcific valvular aortic stenosis; five patients with hypertrophic cardiomyopathy, 11 with mitral prolapse and 33 with significant arterial hypertension (blood pressure greater or equal to 150/96 mm Hg). Eighty-five per cent of the group (68 of 80 patients) had an underlying cardiac disorder associated with either chronically increased left ventricular systolic pressure or abnormal leaflet motion. Other cardiovascular abnormalities occurring as complications secondary to the mitral ring calcification included subacute bacterial endocarditis (three cases), arterial emboli (five episodes) and high grade atrioventricular block (16 cases). Twelve patients had severe mitral regurgitation; successful mitral valve replacement was carried out in four patients (all with myxomatous mitral tissue). Evidence of diffuse conduction system disease, not limited to the area of the cardiac fibrous skeleton, was found frequently (44 patients). Nine patients had sinus node dysfunction and 35 patients had electrocardiographic evidence of distal intraventricular (fascicular) block. Twenty-one patients eventually required pacemakers for management of symptomatic bradyarrhythmias. Atrial fibrillation was present in 23 patients. In this review it was found that calcification of the mitral annulus is frequently associated with or induces serious cardiovascular disease. Since some of these disorders may be modified by appropriate therapy, calcification of the mitral annulus should no longer be ignored as a benign marker of the elderly heart."} {"id": "PMID:156501", "title": "Suppression of mixed lymphocyte reaction by progesterone and estradiol-17beta.", "content": "The effects of estrone, estradiol-17beta, estriol, testosterone, progesterone, and 20alpha-dihydroprogesterone on incorporation of 3H-thymidine into cultured lymphocytes from normal men and nonpregnant women in response to allogeneic stimulation was investigated with two-way MLR. A dose-dependent reduction in the mean percent incorporation was observed in the range of progesterone concentration between 2 x 10(3) and 10(4) ng/ml with statistically significant differences from the control cultures. Estradiol-17 beta at 10(4) ng/ml produced a slight but significant inhibition of incorporation. No significant change in incorporation occurred with the other steroids tested. Since the suppressive property of progesterone in phytohemagglutinin-induced lymphocyte culture reported in our previous communication was reproduced by the present investigation in MLR, the possible role of progesterone in immunoregulation during pregnancy is emphasized as has been postulated previously.", "contents": "Suppression of mixed lymphocyte reaction by progesterone and estradiol-17beta. The effects of estrone, estradiol-17beta, estriol, testosterone, progesterone, and 20alpha-dihydroprogesterone on incorporation of 3H-thymidine into cultured lymphocytes from normal men and nonpregnant women in response to allogeneic stimulation was investigated with two-way MLR. A dose-dependent reduction in the mean percent incorporation was observed in the range of progesterone concentration between 2 x 10(3) and 10(4) ng/ml with statistically significant differences from the control cultures. Estradiol-17 beta at 10(4) ng/ml produced a slight but significant inhibition of incorporation. No significant change in incorporation occurred with the other steroids tested. Since the suppressive property of progesterone in phytohemagglutinin-induced lymphocyte culture reported in our previous communication was reproduced by the present investigation in MLR, the possible role of progesterone in immunoregulation during pregnancy is emphasized as has been postulated previously."} {"id": "PMID:156502", "title": "The dehydroepiandrosterone loading test. III. A possible placental function test.", "content": "The dehydroepiandrosterone loading test (DLT) has been used in a small population of normal and high-risk obstetric patients, to date, in an attempt to develop a dynamic test of placental function. In spite of its limited applications, it has shown reliability in discriminating, with statistical significance, between high-risk pregnancies that result in normally grown, undistressed infants, and high-risk pregnancies that result in infants showing signs of placental insufficiency. The present report expands the study population by presenting our data on 40 loading tests performed in 37 high-risk and normal obstetric patients. Results of 19 of these DLT's have been previously reported and are included herein for statistical analysis. The DLT utilizes an excess substrate load of dehydroepiandrosterone to assess the maximum capability of the placenta to convert it to estrogen. Although our previous report did not show false positive or negative results in the conversion rates, the present results (40 DLT's) found two (2 out of 17) false positives (12%) and two (2 out of 19) false negatives (11%). The highly significant correlation between DLT result and pregnancy outcome seen previously was preserved. In addition, the data of another five DLT's in four patients are presented. This group includes a pregnancy with a fetus with multiple congenital malformations, two patients with intrauterine fetal death, and a nonpregnant woman. The results are not included in the statistical analysis, but discussion of these results has interesting pathophysiologic implications.", "contents": "The dehydroepiandrosterone loading test. III. A possible placental function test. The dehydroepiandrosterone loading test (DLT) has been used in a small population of normal and high-risk obstetric patients, to date, in an attempt to develop a dynamic test of placental function. In spite of its limited applications, it has shown reliability in discriminating, with statistical significance, between high-risk pregnancies that result in normally grown, undistressed infants, and high-risk pregnancies that result in infants showing signs of placental insufficiency. The present report expands the study population by presenting our data on 40 loading tests performed in 37 high-risk and normal obstetric patients. Results of 19 of these DLT's have been previously reported and are included herein for statistical analysis. The DLT utilizes an excess substrate load of dehydroepiandrosterone to assess the maximum capability of the placenta to convert it to estrogen. Although our previous report did not show false positive or negative results in the conversion rates, the present results (40 DLT's) found two (2 out of 17) false positives (12%) and two (2 out of 19) false negatives (11%). The highly significant correlation between DLT result and pregnancy outcome seen previously was preserved. In addition, the data of another five DLT's in four patients are presented. This group includes a pregnancy with a fetus with multiple congenital malformations, two patients with intrauterine fetal death, and a nonpregnant woman. The results are not included in the statistical analysis, but discussion of these results has interesting pathophysiologic implications."} {"id": "PMID:156503", "title": "Delay in growth and the development of nephritis in rats treated with interferon preparations in the neonatal period.", "content": "Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an \"immune complex\" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats.", "contents": "Delay in growth and the development of nephritis in rats treated with interferon preparations in the neonatal period. Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an \"immune complex\" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats."} {"id": "PMID:156504", "title": "Patterns of neuromuscular disease. As related to stages of normal embryogenesis in voluntary muscle.", "content": "Skeletal muscle samples from the upper and lower extremities of 38 human fetuses (6 to 18 weeks' gestation) of both sexes were studied by histologic, histochemical, and electron microscopic methods. Ultrastructural morphometry was applied. In the different stages of normal development are found regressive changes, ranging from reversible dystrophic to irreversible necrotic alterations, which are characteristic of either primary myogenic myopathies or primary neurogenic muscle atrophies in older age. Several pathologic patterns of so-called congenital myopathies also presented. On the basis of their findings, the authors conclude that in a certain group of congenital myopathies full normal development of muscle is hindered or blocked and that groups of muscles or the whole voluntary musculature is arrested at certain stages of maturation. For example, insufficient or absent innervation of the fetal muscle may be a factor in Werdnig-Hoffmann or Kugelberg-Welander syndromes. The authors' findings suggest that pathologic patterns in muscle diseases have been used physiologically in fetal development to eliminate unnecessary overproduction of muscle fibers.", "contents": "Patterns of neuromuscular disease. As related to stages of normal embryogenesis in voluntary muscle. Skeletal muscle samples from the upper and lower extremities of 38 human fetuses (6 to 18 weeks' gestation) of both sexes were studied by histologic, histochemical, and electron microscopic methods. Ultrastructural morphometry was applied. In the different stages of normal development are found regressive changes, ranging from reversible dystrophic to irreversible necrotic alterations, which are characteristic of either primary myogenic myopathies or primary neurogenic muscle atrophies in older age. Several pathologic patterns of so-called congenital myopathies also presented. On the basis of their findings, the authors conclude that in a certain group of congenital myopathies full normal development of muscle is hindered or blocked and that groups of muscles or the whole voluntary musculature is arrested at certain stages of maturation. For example, insufficient or absent innervation of the fetal muscle may be a factor in Werdnig-Hoffmann or Kugelberg-Welander syndromes. The authors' findings suggest that pathologic patterns in muscle diseases have been used physiologically in fetal development to eliminate unnecessary overproduction of muscle fibers."} {"id": "PMID:156506", "title": "Character disorders in traumatized and handicapped children.", "content": "Character disorders in children may arise from abuse or neglect by the family or from stresses of the broader social environment. Physically handicapped and mentally retarded children have innate disabilities that predispose them to problematic interaction with their surroundings. Early professional multidisciplinary intervention can often avert future psychopathy.", "contents": "Character disorders in traumatized and handicapped children. Character disorders in children may arise from abuse or neglect by the family or from stresses of the broader social environment. Physically handicapped and mentally retarded children have innate disabilities that predispose them to problematic interaction with their surroundings. Early professional multidisciplinary intervention can often avert future psychopathy."} {"id": "PMID:156507", "title": "Diocytophymatid larval nematode in a subcutaneous nodule from man in California.", "content": "A nematode in a subcutaneous nodule excised from the chest of a man in central California is described and identified as a third-stage larval dioctophymatid, probably Dioctophyma renale, though a Eustrongylides species could not be excluded. In all well-documented previously reported cases of D. renale infection in man, none of which was from North America, adult worms were discovered in the kidney at autopsy (5 cases), or were observed migrating or being expelled through the urethra (6 cases), discharged through the skin over an abscessed kidney (1 case), or detected by finding eggs in the urine (1 case).", "contents": "Diocytophymatid larval nematode in a subcutaneous nodule from man in California. A nematode in a subcutaneous nodule excised from the chest of a man in central California is described and identified as a third-stage larval dioctophymatid, probably Dioctophyma renale, though a Eustrongylides species could not be excluded. In all well-documented previously reported cases of D. renale infection in man, none of which was from North America, adult worms were discovered in the kidney at autopsy (5 cases), or were observed migrating or being expelled through the urethra (6 cases), discharged through the skin over an abscessed kidney (1 case), or detected by finding eggs in the urine (1 case)."} {"id": "PMID:156508", "title": "Laparoscopy in routine and emergency surgery: experience with 1,720 cases.", "content": "Experience with laparoscopy in 1,720 cases performed for surgical diseases with elective or emergency indications is reported. It is hoped that laparoscopy, a simple and harmless technic of great diagnostic value, will be employed more frequently in routine and emergency surgery.", "contents": "Laparoscopy in routine and emergency surgery: experience with 1,720 cases. Experience with laparoscopy in 1,720 cases performed for surgical diseases with elective or emergency indications is reported. It is hoped that laparoscopy, a simple and harmless technic of great diagnostic value, will be employed more frequently in routine and emergency surgery."} {"id": "PMID:156514", "title": "Daily activity of Tabanidae in the Caucasus.", "content": "The daily activity of Tabanidae (Diptera) was studied in the submountain region of the East Caucasus, district Ismailly, NE Azerbaijan SSR at an altitude 900--1000 m. Tabanidae were collected by the unbaited canopy trap on 8 and 12 July 1976. Females were active from 9 a. m. to 7 p. m., the diurnal biting activity is characterized by a one peak curve with a conspicuous peak of activity between 4 p. m. and 6 p. m. It is suggested that the temperature, relative humidity and the thermic mountain wind are the decisive factors influencing the late afternoon peak of activity. Mating activity of Tabanus unifasciatus at sunrise and of Philipomyia aprica at sunset were observed.", "contents": "Daily activity of Tabanidae in the Caucasus. The daily activity of Tabanidae (Diptera) was studied in the submountain region of the East Caucasus, district Ismailly, NE Azerbaijan SSR at an altitude 900--1000 m. Tabanidae were collected by the unbaited canopy trap on 8 and 12 July 1976. Females were active from 9 a. m. to 7 p. m., the diurnal biting activity is characterized by a one peak curve with a conspicuous peak of activity between 4 p. m. and 6 p. m. It is suggested that the temperature, relative humidity and the thermic mountain wind are the decisive factors influencing the late afternoon peak of activity. Mating activity of Tabanus unifasciatus at sunrise and of Philipomyia aprica at sunset were observed."} {"id": "PMID:156516", "title": "Corneal manifestations of the systemic mucopolysaccharidoses.", "content": "Newer biochemical understanding of the mucopolysaccharidoses now allows a better classification of these diseases. The dermatan and keratan sulfate-storing diseases have corneal clouding. The heparan sulfate-storing diseases have retinal changes and usually central nervous system manifestations.", "contents": "Corneal manifestations of the systemic mucopolysaccharidoses. Newer biochemical understanding of the mucopolysaccharidoses now allows a better classification of these diseases. The dermatan and keratan sulfate-storing diseases have corneal clouding. The heparan sulfate-storing diseases have retinal changes and usually central nervous system manifestations."} {"id": "PMID:156517", "title": "Evidence for the subcellular localization and specificity of chlordane inhibition in the marine bacterium Aeromonas proteolytica.", "content": "Sublethal levels (10 to 100 micrograms/ml) of the chlorinated insecticide chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindan) were introduced into the growth medium of the marine bacterium, Aeromonas proteolytica. Chlordane inhibited the synthesis of an extracellular endopeptidase by almost 40% but exhibited no such inhibition of the extracellular aminopeptidase also produced during the growth cycle. Studied with 14C-labeled chlordane demonstrated that the insecticide was not biologically degraded under the test conditions used and that up to 75% of the recoverable chlordane was cell associated within 48 h. Studied with uniformly labeled L[14C]valine and [2-14C]uracil established that neither the transport nor the incorporation of these protein and ribonucleic acid precursors was inhibited by chlordane. Separation of the membrane fractions using isopycnic centrifugation localized 14C-labeled chlordane in the cytoplasmic membrane. Also, chlordane inhibited the membrane-bound adenosine 5'-triphosphatase while the soluble (released) form of this enzyme remained unaffected. These data indicate that chlordane resides in the cytoplasmic membrane and may cause specific alterations in membrane-associated activities.", "contents": "Evidence for the subcellular localization and specificity of chlordane inhibition in the marine bacterium Aeromonas proteolytica. Sublethal levels (10 to 100 micrograms/ml) of the chlorinated insecticide chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindan) were introduced into the growth medium of the marine bacterium, Aeromonas proteolytica. Chlordane inhibited the synthesis of an extracellular endopeptidase by almost 40% but exhibited no such inhibition of the extracellular aminopeptidase also produced during the growth cycle. Studied with 14C-labeled chlordane demonstrated that the insecticide was not biologically degraded under the test conditions used and that up to 75% of the recoverable chlordane was cell associated within 48 h. Studied with uniformly labeled L[14C]valine and [2-14C]uracil established that neither the transport nor the incorporation of these protein and ribonucleic acid precursors was inhibited by chlordane. Separation of the membrane fractions using isopycnic centrifugation localized 14C-labeled chlordane in the cytoplasmic membrane. Also, chlordane inhibited the membrane-bound adenosine 5'-triphosphatase while the soluble (released) form of this enzyme remained unaffected. These data indicate that chlordane resides in the cytoplasmic membrane and may cause specific alterations in membrane-associated activities."} {"id": "PMID:156518", "title": "Extended clinical use of the argon laser for cutaneous lesions.", "content": "A safe, easy, and effective outpatient modality for the treatment of various cutaneous lesions such as hemangiomas and decorative tattoos has long been sought. The argon laser has proved satisfactory for such treatment of port-wine hemangiomas, capillary/cavernous hemangiomas, telangiectasia, and decorative tattoos as well as a variety of cutaneous pigmented lesions. The intense laser light is attracted and absorbed by pigmented skin lesions producing heat that selectively destroys the intradermal pathologic condition and spares overlying skin. Hemangiomas and tattoos have undergone satisfactory subtotal blanching in the majority of cases with a low incidence of hypertrophic scarring. Thus, the argon laser has proved useful in the outpatient treatment of a variety of pigmented cutaneous lesions.", "contents": "Extended clinical use of the argon laser for cutaneous lesions. A safe, easy, and effective outpatient modality for the treatment of various cutaneous lesions such as hemangiomas and decorative tattoos has long been sought. The argon laser has proved satisfactory for such treatment of port-wine hemangiomas, capillary/cavernous hemangiomas, telangiectasia, and decorative tattoos as well as a variety of cutaneous pigmented lesions. The intense laser light is attracted and absorbed by pigmented skin lesions producing heat that selectively destroys the intradermal pathologic condition and spares overlying skin. Hemangiomas and tattoos have undergone satisfactory subtotal blanching in the majority of cases with a low incidence of hypertrophic scarring. Thus, the argon laser has proved useful in the outpatient treatment of a variety of pigmented cutaneous lesions."} {"id": "PMID:156519", "title": "Hypopigmentation in alopecia mucinosa.", "content": "Alopecia mucinosa was found in the hypopigmented skin of two black patients. Alopecia mucinosa should be included in the differential diagnosis of hypopigmented papular skin lesions.", "contents": "Hypopigmentation in alopecia mucinosa. Alopecia mucinosa was found in the hypopigmented skin of two black patients. Alopecia mucinosa should be included in the differential diagnosis of hypopigmented papular skin lesions."} {"id": "PMID:156520", "title": "Erythema multiforme and urticaria. Eruptions induced by chemically related ophthalmic anticholinergic agents.", "content": "Erythema multiforme developed in an 80-year-old man following the use of scopolamine hydrobromide ophthalmic drops. The erythema multiforme cleared when the medication was discontinued and recurred on challenge. Later, he was given tropicamide, an anticholinergic ophthalmic preparation that, like scopolamine, has a tropic acid residue. Within 15 minutes an immediate hypersensitivity reaction with generalized urticaria developed in the patient.", "contents": "Erythema multiforme and urticaria. Eruptions induced by chemically related ophthalmic anticholinergic agents. Erythema multiforme developed in an 80-year-old man following the use of scopolamine hydrobromide ophthalmic drops. The erythema multiforme cleared when the medication was discontinued and recurred on challenge. Later, he was given tropicamide, an anticholinergic ophthalmic preparation that, like scopolamine, has a tropic acid residue. Within 15 minutes an immediate hypersensitivity reaction with generalized urticaria developed in the patient."} {"id": "PMID:156521", "title": "Acropustulosis of infancy.", "content": "Acropustulosis of infancy (Al) is a syndrome consisting of pruritic pustules that are found primarily on the extremities of infants. It is uncommon, but not rare, and persists about two years. In two infants in whom Al began at birth, there was a striking response to sulfones. There was no response to other therapy. Laboratory findings are not diagnostic for Al. Similar histopathologic changes (subcorneal pustules) can be found in other eruptions of infancy.", "contents": "Acropustulosis of infancy. Acropustulosis of infancy (Al) is a syndrome consisting of pruritic pustules that are found primarily on the extremities of infants. It is uncommon, but not rare, and persists about two years. In two infants in whom Al began at birth, there was a striking response to sulfones. There was no response to other therapy. Laboratory findings are not diagnostic for Al. Similar histopathologic changes (subcorneal pustules) can be found in other eruptions of infancy."} {"id": "PMID:156523", "title": "Postoperative alterations in size of Dacron aortic grafts: an ultrasonic evaluation.", "content": "Reports of aneurysmal dilatation involving Dacron aortic prostheses have raised questions concerning the incidence, degree and significance of postoperative alterations in graft size. Consequently, a study was undertaken to evaluate Dacron graft size by ultrasooud in 95 asymptomatic patients selected at random after aortic surgery. A Vidison Real Time ultrasound unit was used to determine the internal diameter of the aortic portion of the various grafts utilized: 41 Cooley knitted, 25 Vasculour-D; 13 U.S.C.I. ultralightweight; nine Wesolowski Weavenit; and seven DeBakey standard weight knitted. Patients were studied at from two weeks to 138 months postoperatively (average of 33 months). Hypertension was present in 64% of patients. In the total series, the degree of mean dilatation was 17.6%. Average dilatation in patients with normotension was 15% compared to 21% in hypertensive patients. Graphic analysis of the data collected indicated that dilatation of a significant degree occurs in the immediate postoperative period and slowly increases with time; the time regression period and slowly increases with time; the time regression lines for normotensive and hypertensive patients were almost parallel. Results of this clinical study appear to corroborate the results of in vitro quality control tests performed by two graft manufacturers (Meadox and U.S.C.I.).", "contents": "Postoperative alterations in size of Dacron aortic grafts: an ultrasonic evaluation. Reports of aneurysmal dilatation involving Dacron aortic prostheses have raised questions concerning the incidence, degree and significance of postoperative alterations in graft size. Consequently, a study was undertaken to evaluate Dacron graft size by ultrasooud in 95 asymptomatic patients selected at random after aortic surgery. A Vidison Real Time ultrasound unit was used to determine the internal diameter of the aortic portion of the various grafts utilized: 41 Cooley knitted, 25 Vasculour-D; 13 U.S.C.I. ultralightweight; nine Wesolowski Weavenit; and seven DeBakey standard weight knitted. Patients were studied at from two weeks to 138 months postoperatively (average of 33 months). Hypertension was present in 64% of patients. In the total series, the degree of mean dilatation was 17.6%. Average dilatation in patients with normotension was 15% compared to 21% in hypertensive patients. Graphic analysis of the data collected indicated that dilatation of a significant degree occurs in the immediate postoperative period and slowly increases with time; the time regression period and slowly increases with time; the time regression lines for normotensive and hypertensive patients were almost parallel. Results of this clinical study appear to corroborate the results of in vitro quality control tests performed by two graft manufacturers (Meadox and U.S.C.I.)."} {"id": "PMID:156524", "title": "Myocardial hypertrophy: the distribution of cell growth within the layers of the myocardium.", "content": "The spatial distribution of radioactively labeled microspheres was studied in normal and in experimentally hypertrophied hearts of adult pigs. The hearts had been \"tagged\" with microspheres when the pigs were young. When the adult animal was killed, the spatial distribution of the microspheres was identical in the normal and in the hypertrophied hearts. This demonstrates that hypertrophic growth had occurred evenly throughout all layers of the myocardium.", "contents": "Myocardial hypertrophy: the distribution of cell growth within the layers of the myocardium. The spatial distribution of radioactively labeled microspheres was studied in normal and in experimentally hypertrophied hearts of adult pigs. The hearts had been \"tagged\" with microspheres when the pigs were young. When the adult animal was killed, the spatial distribution of the microspheres was identical in the normal and in the hypertrophied hearts. This demonstrates that hypertrophic growth had occurred evenly throughout all layers of the myocardium."} {"id": "PMID:156525", "title": "Graft hemostasis: an alternative to preclotting.", "content": "An alternative to preclotting prosthetic grafts has proved to be simple, safe, and effective in the already heparinized patient. The prosthetic graft or patch is soaked in the patient's blood obtained after systemic heparinization, autoclaved for three minutes at 131 degrees C (270 degrees F), and then inserted.", "contents": "Graft hemostasis: an alternative to preclotting. An alternative to preclotting prosthetic grafts has proved to be simple, safe, and effective in the already heparinized patient. The prosthetic graft or patch is soaked in the patient's blood obtained after systemic heparinization, autoclaved for three minutes at 131 degrees C (270 degrees F), and then inserted."} {"id": "PMID:156526", "title": "Pulsatile perfusion: its effects on blood flow distribution in hypertrophied hearts.", "content": "Left ventricular hypertrophy was created in 15 pigs by banding the ascending aorta when they were young. The adult animals were placed on normothermic cardiopulmonary bypass and perfused with either nonpulsatile (two groups of pigs) or pulsatile (one group) flows. As long as the perfusion rate was maintained at 70 ml/kg/min, myocardial blood flow distribution as determined by radioactive microspheres, was identical in the hearts with normal sinus rhythm and those with ventricular fibrillation irrespective of the type of perfusion. At low flow rates, however, subendocardial ischemia developed in all three groups, but was most severe in the fibrillating hearts, and was not reversed by pulsatile perfusion.", "contents": "Pulsatile perfusion: its effects on blood flow distribution in hypertrophied hearts. Left ventricular hypertrophy was created in 15 pigs by banding the ascending aorta when they were young. The adult animals were placed on normothermic cardiopulmonary bypass and perfused with either nonpulsatile (two groups of pigs) or pulsatile (one group) flows. As long as the perfusion rate was maintained at 70 ml/kg/min, myocardial blood flow distribution as determined by radioactive microspheres, was identical in the hearts with normal sinus rhythm and those with ventricular fibrillation irrespective of the type of perfusion. At low flow rates, however, subendocardial ischemia developed in all three groups, but was most severe in the fibrillating hearts, and was not reversed by pulsatile perfusion."} {"id": "PMID:156528", "title": "Predetermined time standards: their application in workshop settings.", "content": "There is a need for a simple, quickly applied tool which can correlate performance of the handicapped individual with that of the able-bodied worker and be easily utilized by nontechnical personnel. Efforts at both the Cerebral Palsy Center and the Rehabilitation Center in Atlanta demonstrated that the third generation of Methods-Time-Measurement (MTM-3) satisfies these criteria. As every motion involved in an operation is detailed and a corresponding time value applied, the over-all result reflects a normal rate of accomplishment more accurately than the usual methods and is especially useful in bidding jobs for the workshop. MTM-3 also has a place in the evaluation section to verify or correct existing standards on bench-type work samples and to develop more meaningful time distribution charts relating to a specific population at a center. In studies of disabled individuals, MTM-3 yields a more accurate determination of the actual degree of disability than the American Medical Association's existing estimated percentages in regard to motor skills.", "contents": "Predetermined time standards: their application in workshop settings. There is a need for a simple, quickly applied tool which can correlate performance of the handicapped individual with that of the able-bodied worker and be easily utilized by nontechnical personnel. Efforts at both the Cerebral Palsy Center and the Rehabilitation Center in Atlanta demonstrated that the third generation of Methods-Time-Measurement (MTM-3) satisfies these criteria. As every motion involved in an operation is detailed and a corresponding time value applied, the over-all result reflects a normal rate of accomplishment more accurately than the usual methods and is especially useful in bidding jobs for the workshop. MTM-3 also has a place in the evaluation section to verify or correct existing standards on bench-type work samples and to develop more meaningful time distribution charts relating to a specific population at a center. In studies of disabled individuals, MTM-3 yields a more accurate determination of the actual degree of disability than the American Medical Association's existing estimated percentages in regard to motor skills."} {"id": "PMID:156530", "title": "Attitudes of college students toward sexual behavior of disabled persons.", "content": "Empirical data on attitudes toward sexual behavior of disabled persons were gathered from a written, sentence-completion task in which 110 college students engaged. The task consisted of 36 sentence stubs, 18 of which probed attitudes toward sex. To facilitate expression of attitudes rather than values, respondents were instructed to respond rapidly with the first thoughts that came to mind. Responses were scored as positive or negative. Negative responders took significantly less time to complete the sentences than did positive responders. The X2 comparisons of negative responses to 5 pairs of parallel sentence stubs concerned with aspects of sex in general and the same aspects of sex in disabled women yielded statistically significant differences. Four of those differences showed more disapproval of sex for the disabled than for the able-bodied. The 5th difference indicated greater tolerance of homosexual play among disabled girls. On 9 of the 13 sentence stubs concerned with sex and disability, at least 43% of all participants gave negative responses. Similarly, order analysis disclosed that 9 of 10 aspects of sex viewed most negatively were related to sexual behavior by the disabled. It was concluded that attitudes in the sexual revolution have not as yet embraced the disabled even among college students.", "contents": "Attitudes of college students toward sexual behavior of disabled persons. Empirical data on attitudes toward sexual behavior of disabled persons were gathered from a written, sentence-completion task in which 110 college students engaged. The task consisted of 36 sentence stubs, 18 of which probed attitudes toward sex. To facilitate expression of attitudes rather than values, respondents were instructed to respond rapidly with the first thoughts that came to mind. Responses were scored as positive or negative. Negative responders took significantly less time to complete the sentences than did positive responders. The X2 comparisons of negative responses to 5 pairs of parallel sentence stubs concerned with aspects of sex in general and the same aspects of sex in disabled women yielded statistically significant differences. Four of those differences showed more disapproval of sex for the disabled than for the able-bodied. The 5th difference indicated greater tolerance of homosexual play among disabled girls. On 9 of the 13 sentence stubs concerned with sex and disability, at least 43% of all participants gave negative responses. Similarly, order analysis disclosed that 9 of 10 aspects of sex viewed most negatively were related to sexual behavior by the disabled. It was concluded that attitudes in the sexual revolution have not as yet embraced the disabled even among college students."} {"id": "PMID:156531", "title": "A driver training program for the disabled.", "content": "This is a report of results of a driver training program for a selected group of disabled individuals at the Long Beach Veterans Administration Medical Center. A total of 167 eligible candidates elected to enter our driver training program, of whom 154 (92%) were successful. Dropouts were the result of educational deficiencies, physical inability, and/or stress in performance ability.", "contents": "A driver training program for the disabled. This is a report of results of a driver training program for a selected group of disabled individuals at the Long Beach Veterans Administration Medical Center. A total of 167 eligible candidates elected to enter our driver training program, of whom 154 (92%) were successful. Dropouts were the result of educational deficiencies, physical inability, and/or stress in performance ability."} {"id": "PMID:156532", "title": "Seeding endothelium onto canine arterial prostheses. The effects of graft design.", "content": "To identify prosthetic characteristics that support the proliferation of an endothelial lining, 14 different graft designs were studied in dogs. The grafts were prepared by the use of a technique of endothelial seeding that we described previously. They were studied two and four weeks after their implantation. Weft-knit Dacron grafts (water porosity from 1,400 to 1,650 mL/min/sq cm) were the most successful. A velour index (velour stitch frequency times velour loop height) was computed. When the internal velour index (IVI) was greater than 60,000 loop-mu/sq cm, the percentage of clot-free surface was 17.2 +/- 14.5%, compared with 62.0 +/- 26.9% when the IVI less than 60,000 loop-mu/sq cm. Endothelium could be detected on 61.5% of the grafts when the IVI less than 60,00 loop-mu/sq cm, compared with 0% when the IVI greater than 60,000 loop-mu/sq cm. The cells that formed the outer capsule were better organized and more adherent to the graft when an external velour was present, but external velour did not affect the inner lining. We conclude that weft-knit Dacron grafts with water porosities from 1,400 to 1,650 mL/min/sq cm and with limited internal velour (IVI less than 60,000 loop-mu/sq cm) are suitable substrates for single-staged endothelial-cell seeding.", "contents": "Seeding endothelium onto canine arterial prostheses. The effects of graft design. To identify prosthetic characteristics that support the proliferation of an endothelial lining, 14 different graft designs were studied in dogs. The grafts were prepared by the use of a technique of endothelial seeding that we described previously. They were studied two and four weeks after their implantation. Weft-knit Dacron grafts (water porosity from 1,400 to 1,650 mL/min/sq cm) were the most successful. A velour index (velour stitch frequency times velour loop height) was computed. When the internal velour index (IVI) was greater than 60,000 loop-mu/sq cm, the percentage of clot-free surface was 17.2 +/- 14.5%, compared with 62.0 +/- 26.9% when the IVI less than 60,000 loop-mu/sq cm. Endothelium could be detected on 61.5% of the grafts when the IVI less than 60,00 loop-mu/sq cm, compared with 0% when the IVI greater than 60,000 loop-mu/sq cm. The cells that formed the outer capsule were better organized and more adherent to the graft when an external velour was present, but external velour did not affect the inner lining. We conclude that weft-knit Dacron grafts with water porosities from 1,400 to 1,650 mL/min/sq cm and with limited internal velour (IVI less than 60,000 loop-mu/sq cm) are suitable substrates for single-staged endothelial-cell seeding."} {"id": "PMID:156533", "title": "Current arterial prostheses. Experimental evaluation by implantation in the carotid and circumflex coronary arteries of the dog.", "content": "Five types of 4-mm diameter arterial prostheses (three Dacron, one expanded Teflon, one preserved umbilical vein) were studied in the dog to assess graft thrombogenicity. Separate experiments involving six hours of controlled blood flow, one-week carotid implantation, and aortocoronary implantation were performed. In general, graft thrombogenicity derived from controlled flow study was more predictive of a graft's long-term implantation success than were one-week implantation results. In order of increasing thrombogenicity, we ranked grafts studied as follows: noncrimped Dacron, expanded Teflon, crimped Dacron, umbilical vein. Results of 19 experimental left coronary artery implantations using Dacron or Teflon prostheses are reported that indicate grafts with low measured thrombogenicity are most likely to succeed in this site. Data presented in this report suggest there is reason to evaluate noncrimped, kink-resistant, porous Dacron grafts for use both in the left coronary artery and below the knee when there is compelling clinical indication and no autogenous vessels are available.", "contents": "Current arterial prostheses. Experimental evaluation by implantation in the carotid and circumflex coronary arteries of the dog. Five types of 4-mm diameter arterial prostheses (three Dacron, one expanded Teflon, one preserved umbilical vein) were studied in the dog to assess graft thrombogenicity. Separate experiments involving six hours of controlled blood flow, one-week carotid implantation, and aortocoronary implantation were performed. In general, graft thrombogenicity derived from controlled flow study was more predictive of a graft's long-term implantation success than were one-week implantation results. In order of increasing thrombogenicity, we ranked grafts studied as follows: noncrimped Dacron, expanded Teflon, crimped Dacron, umbilical vein. Results of 19 experimental left coronary artery implantations using Dacron or Teflon prostheses are reported that indicate grafts with low measured thrombogenicity are most likely to succeed in this site. Data presented in this report suggest there is reason to evaluate noncrimped, kink-resistant, porous Dacron grafts for use both in the left coronary artery and below the knee when there is compelling clinical indication and no autogenous vessels are available."} {"id": "PMID:156534", "title": "Ureteral obstruction secondary to bifurcated aortic grafts.", "content": "We report three cases of ureteral obstruction producing hydronephrosis following aortofemoral bypass graft. In each case, the obstruction occurred in the area where in the ureter crossed over the limb of a Dacron graft. Ureterolysis relieved the obstruction. Most of the previously reported cases of this complication of bypass surgery occurred when the ureter was situated between the limb of a graft and the patient's own iliac artery. Various methods of surgical appraoch are listed. In some cases, ureterolysis is a suitable alternative to division and reanastomosis of the ureter to relieve obstruction.", "contents": "Ureteral obstruction secondary to bifurcated aortic grafts. We report three cases of ureteral obstruction producing hydronephrosis following aortofemoral bypass graft. In each case, the obstruction occurred in the area where in the ureter crossed over the limb of a Dacron graft. Ureterolysis relieved the obstruction. Most of the previously reported cases of this complication of bypass surgery occurred when the ureter was situated between the limb of a graft and the patient's own iliac artery. Various methods of surgical appraoch are listed. In some cases, ureterolysis is a suitable alternative to division and reanastomosis of the ureter to relieve obstruction."} {"id": "PMID:156535", "title": "Sedative effects of apomorphine in an animal model of Huntington's disease.", "content": "The sedative effectiveness of apomorphine in a newly developed animal model of Huntington's disease was examined. The motor responses of rats with kainic acid lesions of the neostriatum to a sedative dose of apomorphine (50 micrograms/kg) was similar to that observed in intact controls. In contrast, compared to controls, a marked potentiation of the motor stimulant effects of dextroamphetamine was confirmed in the kainic acid-lesioned group. We suggest that the pathological changes underlying the symptoms observed in this animal model and in Huntington's disease do not include abnormalities in presynaptic dopamine receptors in the neostriatum.", "contents": "Sedative effects of apomorphine in an animal model of Huntington's disease. The sedative effectiveness of apomorphine in a newly developed animal model of Huntington's disease was examined. The motor responses of rats with kainic acid lesions of the neostriatum to a sedative dose of apomorphine (50 micrograms/kg) was similar to that observed in intact controls. In contrast, compared to controls, a marked potentiation of the motor stimulant effects of dextroamphetamine was confirmed in the kainic acid-lesioned group. We suggest that the pathological changes underlying the symptoms observed in this animal model and in Huntington's disease do not include abnormalities in presynaptic dopamine receptors in the neostriatum."} {"id": "PMID:156538", "title": "Changes in the immunoglobulin levels of the mouse gut and serum during conventionalisation and following administration of Salmonella typhimurium.", "content": "Increasess in all immunoglobulin classes, except IgM, were observed in the sera of specific pathogen-free (SPF) mice beginning 10 days after their removal from barrier conditions. Concentrations of serum immunoglobulins, comparable with those of conventional mice, were obtained in these animals between 21 and 35 days. Following the removal of germ-free mice from their sterile isolaters, their intestinal IgA levels increased over 35 days to attain levels found in conventional animals. A marked increase in serum immunoglobulin occurred within one day following intravenous administration of live Salmonella typhimurium organisms to SPF animals, and this persisted for longer than 7 weeks (the duration of the study), This rapid elevation in serum immunoglobulin was not elicited by nonbacterial antigens, killed Salmonellae, or viable Vibrio cholerae. Negligible amounts of this immunoglobulin increase could be attributed to specific antibody.", "contents": "Changes in the immunoglobulin levels of the mouse gut and serum during conventionalisation and following administration of Salmonella typhimurium. Increasess in all immunoglobulin classes, except IgM, were observed in the sera of specific pathogen-free (SPF) mice beginning 10 days after their removal from barrier conditions. Concentrations of serum immunoglobulins, comparable with those of conventional mice, were obtained in these animals between 21 and 35 days. Following the removal of germ-free mice from their sterile isolaters, their intestinal IgA levels increased over 35 days to attain levels found in conventional animals. A marked increase in serum immunoglobulin occurred within one day following intravenous administration of live Salmonella typhimurium organisms to SPF animals, and this persisted for longer than 7 weeks (the duration of the study), This rapid elevation in serum immunoglobulin was not elicited by nonbacterial antigens, killed Salmonellae, or viable Vibrio cholerae. Negligible amounts of this immunoglobulin increase could be attributed to specific antibody."} {"id": "PMID:156540", "title": "Serum immune complexes and disease.", "content": "The solid phase Clq radioimmunoassay was used to detect immune complexes in sera from patients with systemic lupus erythematosus (14/25), rheumatoid arthritis (4/5), vasculitis (5/15), infective endocarditis (2/2), acute rheumatic fever (2/3), pre-eclamptic toxaemia (0/14), lung cancer (3/7), glomerulonephritis (26/98) and renal transplant patients (0/5). The best correlation with disease activity was seen in systemic lupus erythematosus and infective endocarditis where serial immune complex determinations were clearly of value in monitoring therapy. The findings in primary glomerulonephritis indicate only a limited usefulness of the assay in that serum immune complexes were detected in a minority (22/73) of patients with glomerular immune deposits. In particular the data do not support a role for Clq fixing immune complexes in the pathogenesis of membranous glomerulonephritis or in pre-eclamptic toxaemia.", "contents": "Serum immune complexes and disease. The solid phase Clq radioimmunoassay was used to detect immune complexes in sera from patients with systemic lupus erythematosus (14/25), rheumatoid arthritis (4/5), vasculitis (5/15), infective endocarditis (2/2), acute rheumatic fever (2/3), pre-eclamptic toxaemia (0/14), lung cancer (3/7), glomerulonephritis (26/98) and renal transplant patients (0/5). The best correlation with disease activity was seen in systemic lupus erythematosus and infective endocarditis where serial immune complex determinations were clearly of value in monitoring therapy. The findings in primary glomerulonephritis indicate only a limited usefulness of the assay in that serum immune complexes were detected in a minority (22/73) of patients with glomerular immune deposits. In particular the data do not support a role for Clq fixing immune complexes in the pathogenesis of membranous glomerulonephritis or in pre-eclamptic toxaemia."} {"id": "PMID:156547", "title": "Studies of immune functions of patients with systemic lupus erythematosus.", "content": "In normal individuals T cells are stimulated to proliferate by autologous non-T cells; this is called the autologous mixed lymphocyte reaction (MLR). Previous studies demonstrated that such an autologous MLR was markedly impaired in patients with active systemic lupus erythematosus (SLE). To determine whether the defect resided in the responding cell or the stimulating cell, mixing experiments were performed using cells from identical twins. We identified two sets of identical twins discordant for SLE activity and correspondingly discordant in their degree of responsiveness in the autologous MLR. Reciprocal mixing experiments were performed in which T cells from one twin of each pair were mixed with non-T cells from the other twin of that pair. These studies indicated that patients with active SLE have a defect in the ability of non-T cells to stimulate as well as a defect in the ability of both Tgamma and Tnongamma cells to respond in the autologous MLR. Patients with inactive SLE have a defect only in responsiveness of Tgamma cells.", "contents": "Studies of immune functions of patients with systemic lupus erythematosus. In normal individuals T cells are stimulated to proliferate by autologous non-T cells; this is called the autologous mixed lymphocyte reaction (MLR). Previous studies demonstrated that such an autologous MLR was markedly impaired in patients with active systemic lupus erythematosus (SLE). To determine whether the defect resided in the responding cell or the stimulating cell, mixing experiments were performed using cells from identical twins. We identified two sets of identical twins discordant for SLE activity and correspondingly discordant in their degree of responsiveness in the autologous MLR. Reciprocal mixing experiments were performed in which T cells from one twin of each pair were mixed with non-T cells from the other twin of that pair. These studies indicated that patients with active SLE have a defect in the ability of non-T cells to stimulate as well as a defect in the ability of both Tgamma and Tnongamma cells to respond in the autologous MLR. Patients with inactive SLE have a defect only in responsiveness of Tgamma cells."} {"id": "PMID:156553", "title": "Hair casts.", "content": "The literature on hair casts suggests they are rare even though Kligman intimated in 1957 that in some scalp diseases they might well be common. In this study, casts have been looked for in a group of orthokeratotic and parakeratotic scalp conditions. Hair casts are indeed common in psoriasis, pityriasis amiantacea, pityriasis capitis and seborrhoeic dermatitis. No casts were seen in women with traction hair styles or in those regularly using hair sprays.", "contents": "Hair casts. The literature on hair casts suggests they are rare even though Kligman intimated in 1957 that in some scalp diseases they might well be common. In this study, casts have been looked for in a group of orthokeratotic and parakeratotic scalp conditions. Hair casts are indeed common in psoriasis, pityriasis amiantacea, pityriasis capitis and seborrhoeic dermatitis. No casts were seen in women with traction hair styles or in those regularly using hair sprays."} {"id": "PMID:156554", "title": "Contact dermatitis and gastrointestinal symptoms from hydroxyethylmethacrylate.", "content": "A laboratory technician developed allergic contact dermatitis to hydroxyethylmethacrylate associated with nausea, diarrhoea and persistent paresthesiae of the fingertips. The gastrointestinal symptoms were reproduced by patch testing. Hydroxyethylmethacrylate was demonstrated to pass through vinyl gloves. Cross reactions occurred to methyl-, ethyl-, propyl- and isopropylmethacrylate but not to butyl- or isobutylmethacrylate.", "contents": "Contact dermatitis and gastrointestinal symptoms from hydroxyethylmethacrylate. A laboratory technician developed allergic contact dermatitis to hydroxyethylmethacrylate associated with nausea, diarrhoea and persistent paresthesiae of the fingertips. The gastrointestinal symptoms were reproduced by patch testing. Hydroxyethylmethacrylate was demonstrated to pass through vinyl gloves. Cross reactions occurred to methyl-, ethyl-, propyl- and isopropylmethacrylate but not to butyl- or isobutylmethacrylate."} {"id": "PMID:156555", "title": "Properties of ATP-induced chlorophyll luminescence in chloroplasts.", "content": "1. The recently described reaction of ATP-induced luminescence is analyzed for its relation to other ATP-induced reactions such as ATP-driven transmembrane proton gradient formation and ATP-driven reverse electron flow. 2. In the absence of phenazine methosulfate ATP-induced luminescence is optimal while the main phase of ATP-driven reverse electron flow is eliminated. 3. DCMU which by itself causes a much smaller luminescence, inhibits the ATP-induced luminescence. 4. Nigericin plus valinomycin, but not each by itself, fully inhibit the ATP-induced luminescence. 5. The observations are interpreted as indicating that ATP stimulates luminescence by a 2-fold mechanism: (a) increasing the amount of the reducing primary electron acceptor of Photosystem II, Q, and (b) creating a transmembrane electrochemical potential which serves to decrease the activation energy required for the charge recombination reaction which leads to luminescence.", "contents": "Properties of ATP-induced chlorophyll luminescence in chloroplasts. 1. The recently described reaction of ATP-induced luminescence is analyzed for its relation to other ATP-induced reactions such as ATP-driven transmembrane proton gradient formation and ATP-driven reverse electron flow. 2. In the absence of phenazine methosulfate ATP-induced luminescence is optimal while the main phase of ATP-driven reverse electron flow is eliminated. 3. DCMU which by itself causes a much smaller luminescence, inhibits the ATP-induced luminescence. 4. Nigericin plus valinomycin, but not each by itself, fully inhibit the ATP-induced luminescence. 5. The observations are interpreted as indicating that ATP stimulates luminescence by a 2-fold mechanism: (a) increasing the amount of the reducing primary electron acceptor of Photosystem II, Q, and (b) creating a transmembrane electrochemical potential which serves to decrease the activation energy required for the charge recombination reaction which leads to luminescence."} {"id": "PMID:156556", "title": "Solubility characteristics of Micrococcus lysodeikticus membrane components in detergents and chaotropic salts analyzed by immunoelectrophoresis.", "content": "In order to evalute the effectiveness and selectivity of various reagents in the solubilization of bacterial membranes, membranes of Micrococcus lysodeikticus were treated with detergents and chaotropic agents. The composition of the extracts so obtained was analyzed by rocket and two-dimensional immunoelectrophoretic techniques. Recoveery of succinate-, malate-, and reduced nicotinamide adenine dinucleotide- (NADH) dehydrogenases, ATPase, succinylated lipomannan and cytochromes in the extracts was measured. Treatment with a variety of non-denaturing detergents produced extracts that were generally qualitatively uniform although quantitative differences were observed. The degree of extraction of various components was correlated with the hydrophile-lipophile balance. Several chaotropic agents were also evaluated as reagents for membrane solubilization. These agents were less effective in extraction of bulk protein, but produced extracts enriched in some membrane components.", "contents": "Solubility characteristics of Micrococcus lysodeikticus membrane components in detergents and chaotropic salts analyzed by immunoelectrophoresis. In order to evalute the effectiveness and selectivity of various reagents in the solubilization of bacterial membranes, membranes of Micrococcus lysodeikticus were treated with detergents and chaotropic agents. The composition of the extracts so obtained was analyzed by rocket and two-dimensional immunoelectrophoretic techniques. Recoveery of succinate-, malate-, and reduced nicotinamide adenine dinucleotide- (NADH) dehydrogenases, ATPase, succinylated lipomannan and cytochromes in the extracts was measured. Treatment with a variety of non-denaturing detergents produced extracts that were generally qualitatively uniform although quantitative differences were observed. The degree of extraction of various components was correlated with the hydrophile-lipophile balance. Several chaotropic agents were also evaluated as reagents for membrane solubilization. These agents were less effective in extraction of bulk protein, but produced extracts enriched in some membrane components."} {"id": "PMID:156558", "title": "Ca2+-dependent ATPase activity of alveolar macrophage plasma membrane.", "content": "A plasma membrane fraction was isolated from lysates of Bacillus Calmette-Gu\u00e9rin-induced alveolar macrophages of rabbit. On the basis of morphological and biochemical criteria this fraction appeared to be minimally contaminated by other subcellular organelles. Concentrations of Ca2+, but not of Mg2+, from 6.10(-8) to 1.10(-5) M markedly stimulated the basal ATPase (EC 3.6.1.3) activity of the plasma membrane, with an apparent Km (Ca2+) of 1.10(-6) M. The specific activity of the Ca2+-ATPase assayed at pCa = 5.5 was enriched about 8-fold in the plasma membrane fraction over the macrophage lysate. In contrast, the specific activity of the K+, EDTA-activated ATPase, associated to macrophage myosin, increased only 1.3-fold. Oligomycin and -SH group reagents exerted no influence on the Ca2+-ATPase activity, which was on the contrary inhibited by detergents such as Triton X-100 and deoxycholate. The activity of the Ca2+-ATPase was maximal at pH 7, and was decreased by 50 mM Na+ and 5 mM K+. On the contrary, the activity of Mg2+-ATPase, also present in the plasma membrane fraction, had a peak at about pH 7.8, and was stimulated by Na+ plus K+. On account of its properties, it is suggested that the Ca2+-ATPase is a component of the plasma membrane of the alveolar macrophage, and that its function may be that of participating in the maintenance of low free Ca2+ concentrations in the macrophage cytosol.", "contents": "Ca2+-dependent ATPase activity of alveolar macrophage plasma membrane. A plasma membrane fraction was isolated from lysates of Bacillus Calmette-Gu\u00e9rin-induced alveolar macrophages of rabbit. On the basis of morphological and biochemical criteria this fraction appeared to be minimally contaminated by other subcellular organelles. Concentrations of Ca2+, but not of Mg2+, from 6.10(-8) to 1.10(-5) M markedly stimulated the basal ATPase (EC 3.6.1.3) activity of the plasma membrane, with an apparent Km (Ca2+) of 1.10(-6) M. The specific activity of the Ca2+-ATPase assayed at pCa = 5.5 was enriched about 8-fold in the plasma membrane fraction over the macrophage lysate. In contrast, the specific activity of the K+, EDTA-activated ATPase, associated to macrophage myosin, increased only 1.3-fold. Oligomycin and -SH group reagents exerted no influence on the Ca2+-ATPase activity, which was on the contrary inhibited by detergents such as Triton X-100 and deoxycholate. The activity of the Ca2+-ATPase was maximal at pH 7, and was decreased by 50 mM Na+ and 5 mM K+. On the contrary, the activity of Mg2+-ATPase, also present in the plasma membrane fraction, had a peak at about pH 7.8, and was stimulated by Na+ plus K+. On account of its properties, it is suggested that the Ca2+-ATPase is a component of the plasma membrane of the alveolar macrophage, and that its function may be that of participating in the maintenance of low free Ca2+ concentrations in the macrophage cytosol."} {"id": "PMID:156559", "title": "Purification of the arom multienzyme aggregate from Euglena gracilis.", "content": "The arom multienzyme complex that catalyzes steps two through six in the prechorismate polyaromatic amino acid biosynthetic pathway has been purified up to 2000-fold from Euglena gracilis. The native arom aggregate has a molecular weight of approx. 249 000 based on a sedimentation coefficient of 9.5 and Stokes radius of 60 angstrom. A comparison between the arom aggregates of Neurospora crassa and Euglena gracilis and the possible phylogenetic relationships between the organisms are discussed.", "contents": "Purification of the arom multienzyme aggregate from Euglena gracilis. The arom multienzyme complex that catalyzes steps two through six in the prechorismate polyaromatic amino acid biosynthetic pathway has been purified up to 2000-fold from Euglena gracilis. The native arom aggregate has a molecular weight of approx. 249 000 based on a sedimentation coefficient of 9.5 and Stokes radius of 60 angstrom. A comparison between the arom aggregates of Neurospora crassa and Euglena gracilis and the possible phylogenetic relationships between the organisms are discussed."} {"id": "PMID:156560", "title": "Enzymatic activities and ATP-induced fluorescence enhancement of myosin from fast and slow skeletal and cardiac muscles.", "content": "The maximal ATP-induced enhancement of fluorescence and the dependence of this enhancement on ATP concentration were determined for myosins from fast and slow skeletal and cardiac muscle of the rabbit. With myosins from slow and cardiac muscle modifications in the preparative procedure and chromatography on DEAE-Sephadex were required to obtain preprations which were free of actin, which exhibited the maximal fluorescence enhancement and which bound two moles of ATP per mole of myosin. Since the fluorescence enhancement of cardiac and slow muscle myosins is labile at slightly alkaline pH, it was also necessary to minimize incubation at pH greater than 7 in order to attain the maximal enhancement. With fast muscle myosin the changes in preparative procedure, together with chromatography, led to a 50 to 100% increase in the steady-state rate of ATP hydrolysis and fluorescence enhancement, without changing the maximal binding of ATP. From a comparison of the rate of steady-state hydrolysis of ATP with the rate of decay of the enhanced fluorescence, it appears that for all three myosins, both ATP binding sites have the same enzymatic activity, the steady-state rate per site being slower for cardiac and slow muscle myosins than for fast muscle myosin.", "contents": "Enzymatic activities and ATP-induced fluorescence enhancement of myosin from fast and slow skeletal and cardiac muscles. The maximal ATP-induced enhancement of fluorescence and the dependence of this enhancement on ATP concentration were determined for myosins from fast and slow skeletal and cardiac muscle of the rabbit. With myosins from slow and cardiac muscle modifications in the preparative procedure and chromatography on DEAE-Sephadex were required to obtain preprations which were free of actin, which exhibited the maximal fluorescence enhancement and which bound two moles of ATP per mole of myosin. Since the fluorescence enhancement of cardiac and slow muscle myosins is labile at slightly alkaline pH, it was also necessary to minimize incubation at pH greater than 7 in order to attain the maximal enhancement. With fast muscle myosin the changes in preparative procedure, together with chromatography, led to a 50 to 100% increase in the steady-state rate of ATP hydrolysis and fluorescence enhancement, without changing the maximal binding of ATP. From a comparison of the rate of steady-state hydrolysis of ATP with the rate of decay of the enhanced fluorescence, it appears that for all three myosins, both ATP binding sites have the same enzymatic activity, the steady-state rate per site being slower for cardiac and slow muscle myosins than for fast muscle myosin."} {"id": "PMID:156561", "title": "Protein-protein interactions of proteolytic fragments of actin.", "content": "Proteolytic fragments of actin, prepared by removal of up to sixty-eight residues from the N-terminal end of the molecule, can form filamentous structures after denaturation in urea solution. The filaments have a diameter similar to F-actin filaments and interact with myosin and tropomyosin. A fragment comprising residues 1 to 207 of the actin sequence did not form filaments or interact with myosin after the urea treatment.", "contents": "Protein-protein interactions of proteolytic fragments of actin. Proteolytic fragments of actin, prepared by removal of up to sixty-eight residues from the N-terminal end of the molecule, can form filamentous structures after denaturation in urea solution. The filaments have a diameter similar to F-actin filaments and interact with myosin and tropomyosin. A fragment comprising residues 1 to 207 of the actin sequence did not form filaments or interact with myosin after the urea treatment."} {"id": "PMID:156562", "title": "Studies of dynein from Tetrahymena cilia using agarose polyacrylamide gel electrophoresis.", "content": "Described in this report is an application of agarose-polyacrylamide gel electrophoresis, which separates protein components of crude dynein fraction (Fraction I by Gibbons) derived from Tetrahymena cilia. By this method, the fraction was separated into three protein components (designated as bands I, II and III) on the gel. When the gel was actively stained for dynein ATPase, a single band appeared, which coincided with the position of band I. A purified dynein prepared by controlled pore glass (CPG-10) column chromatography and followed by Biogel A-15m filtration showed one band on the gel at the same position as band I. These results suggest that among these three protein components, band I represents dynein and bands II and III are derived form non-ATPase protein. 'Burstic phenomenon' was also observed on their ATPase activity when axoneme or crude dynein fractions were used for ATPase assay, while the phenomenon was almost extinguished when partially purified dynein after controlled pore glass column chromatography was used as sample.", "contents": "Studies of dynein from Tetrahymena cilia using agarose polyacrylamide gel electrophoresis. Described in this report is an application of agarose-polyacrylamide gel electrophoresis, which separates protein components of crude dynein fraction (Fraction I by Gibbons) derived from Tetrahymena cilia. By this method, the fraction was separated into three protein components (designated as bands I, II and III) on the gel. When the gel was actively stained for dynein ATPase, a single band appeared, which coincided with the position of band I. A purified dynein prepared by controlled pore glass (CPG-10) column chromatography and followed by Biogel A-15m filtration showed one band on the gel at the same position as band I. These results suggest that among these three protein components, band I represents dynein and bands II and III are derived form non-ATPase protein. 'Burstic phenomenon' was also observed on their ATPase activity when axoneme or crude dynein fractions were used for ATPase assay, while the phenomenon was almost extinguished when partially purified dynein after controlled pore glass column chromatography was used as sample."} {"id": "PMID:156563", "title": "[Effects of neutral salts and temperature on skeletal muscle sarcolemmal Ca-TPase].", "content": "The temperature dependence and effects of sodium and potassium chloride on purified preparations of sarcolemmal Ca2+-activated ATPase were investigated. It was shown that within the concentration range of 0,1--1,0 M both salts have the same effect on the enzyme activity. A low ionic strength and concentration of the salts of 0,1 M the temperature maximum was 45 degrees and the shapes of temperature curves were the same. The Arrhenius plots showed a break at 16--19 degrees. The apparent activation energies were 27,3 kcal/mole below and 17,1 kcal/mole above the break point. At high ionic strength (0,5 M) the temperature maximum was observed at 40 degrees and the apparent activation energies decreased down to 18,0 kcal/mole below and 11,5 kcal/mole above the break point.", "contents": "[Effects of neutral salts and temperature on skeletal muscle sarcolemmal Ca-TPase]. The temperature dependence and effects of sodium and potassium chloride on purified preparations of sarcolemmal Ca2+-activated ATPase were investigated. It was shown that within the concentration range of 0,1--1,0 M both salts have the same effect on the enzyme activity. A low ionic strength and concentration of the salts of 0,1 M the temperature maximum was 45 degrees and the shapes of temperature curves were the same. The Arrhenius plots showed a break at 16--19 degrees. The apparent activation energies were 27,3 kcal/mole below and 17,1 kcal/mole above the break point. At high ionic strength (0,5 M) the temperature maximum was observed at 40 degrees and the apparent activation energies decreased down to 18,0 kcal/mole below and 11,5 kcal/mole above the break point."} {"id": "PMID:156564", "title": "[Temperature-dependent changes in the profile of the sarcoplasmic reticulum membrane hydrophobic zones].", "content": "The dependence of the state of the hydrophobic zone of rabbit sarcoplasmic reticulum (SR) membranes on temperature of the membrane fragment suspension before rapid freezing was studied by the freeze fracturing technique. It was shown that within the temperature range of--15-- +37 degrees C the amount of intramembrane particles and their distribution in the membrane plane and between their convex and concave surfaces do not practically depend on the temperature of the SR membrane suspension. This is indicative of the lack of correlation between the physical state of the phospholipid matrix (gel -- liquid crystal) before freezing and the nature of the profile of the membrane hydrophobic zone revealed after fracturing. The disturbances in the protein -- lipid interactions in the membrane under the effects of mersalyl or aqueous solutions of diethyl ester followed by complete inactivation of Ca2+-dependent ATPase lead to a decrease in the amount of intramembrane particles, which is especially well-pronounced at 37 degrees and -15 degrees C.", "contents": "[Temperature-dependent changes in the profile of the sarcoplasmic reticulum membrane hydrophobic zones]. The dependence of the state of the hydrophobic zone of rabbit sarcoplasmic reticulum (SR) membranes on temperature of the membrane fragment suspension before rapid freezing was studied by the freeze fracturing technique. It was shown that within the temperature range of--15-- +37 degrees C the amount of intramembrane particles and their distribution in the membrane plane and between their convex and concave surfaces do not practically depend on the temperature of the SR membrane suspension. This is indicative of the lack of correlation between the physical state of the phospholipid matrix (gel -- liquid crystal) before freezing and the nature of the profile of the membrane hydrophobic zone revealed after fracturing. The disturbances in the protein -- lipid interactions in the membrane under the effects of mersalyl or aqueous solutions of diethyl ester followed by complete inactivation of Ca2+-dependent ATPase lead to a decrease in the amount of intramembrane particles, which is especially well-pronounced at 37 degrees and -15 degrees C."} {"id": "PMID:156565", "title": "Bio-materials science and technology.", "content": "Materials in current use resulting from clinical acceptance are reviewed. Requirements for a bio-material are considered and problem areas still awaiting solution are identified. These include fatigue, wear, corrosion and adverse tissue effects. The question of relating the structure of materials to their in-vivo properties and the application of this to development of bio-materials is next considered. The properties of the tissues and the way in which newer materials are better adapted to the dynamic properties of these is discussed and future developments are considered in the light of this.", "contents": "Bio-materials science and technology. Materials in current use resulting from clinical acceptance are reviewed. Requirements for a bio-material are considered and problem areas still awaiting solution are identified. These include fatigue, wear, corrosion and adverse tissue effects. The question of relating the structure of materials to their in-vivo properties and the application of this to development of bio-materials is next considered. The properties of the tissues and the way in which newer materials are better adapted to the dynamic properties of these is discussed and future developments are considered in the light of this."} {"id": "PMID:156568", "title": "Phosphofructokinase in human blood cells.", "content": "The subunit composition of phosphofructokinase from normal and malignant blood cells has been investigated by means of immunologic, electrophoretic, and chromatographic methods. Immunoprecipitation tests were performed with three specific antisera recognizing each of the basic subunits of human phosphofructokinase: muscle, M-type; liver, L-type; and fibroblast, F-type. Mature polymorphonuclear cells contain mainly L-subunits, while lymphocytes and platelets contain hybrids formed of L and F subunits; these hybrids can be electrophoretically separated. Red cell phosphofructokinase is composed of L and M subunits, as judged by its reactivity with anti-L and anti-M-type antisera. The various M-L hybrids composing red cell phosphofructokinase could be only separated by chromatography on DEAE-Cellulose. Lymphocytes from patients with chronic lymphocytic leukemia and lymphoblasts from patients with acute lymphoblastic leukemia contain phosphofructokinase forms similar to those from normal lymphocytes, while the immature granulocytic cells (leukemic myeloblasts and myeloid cells of chronic myeloid leukemia) are characterized by a reinforcement of enzyme inhibition by anti-F-type antiserum. Lymphoid lines in culture (Epstein-Barr virus (EBV)-induced or malignant lymphoma-derived lines) are characterized by the indistinctive expression of all three basic subunits, similar to that found in some fetal tissues. This article represents the first description of the isozymic nature of phosphofructokinase in platelets and white blood cells and of its changes with malignancy and cell culture. This enzyme might represent a useful marker in the characterization of the leukemic cells.", "contents": "Phosphofructokinase in human blood cells. The subunit composition of phosphofructokinase from normal and malignant blood cells has been investigated by means of immunologic, electrophoretic, and chromatographic methods. Immunoprecipitation tests were performed with three specific antisera recognizing each of the basic subunits of human phosphofructokinase: muscle, M-type; liver, L-type; and fibroblast, F-type. Mature polymorphonuclear cells contain mainly L-subunits, while lymphocytes and platelets contain hybrids formed of L and F subunits; these hybrids can be electrophoretically separated. Red cell phosphofructokinase is composed of L and M subunits, as judged by its reactivity with anti-L and anti-M-type antisera. The various M-L hybrids composing red cell phosphofructokinase could be only separated by chromatography on DEAE-Cellulose. Lymphocytes from patients with chronic lymphocytic leukemia and lymphoblasts from patients with acute lymphoblastic leukemia contain phosphofructokinase forms similar to those from normal lymphocytes, while the immature granulocytic cells (leukemic myeloblasts and myeloid cells of chronic myeloid leukemia) are characterized by a reinforcement of enzyme inhibition by anti-F-type antiserum. Lymphoid lines in culture (Epstein-Barr virus (EBV)-induced or malignant lymphoma-derived lines) are characterized by the indistinctive expression of all three basic subunits, similar to that found in some fetal tissues. This article represents the first description of the isozymic nature of phosphofructokinase in platelets and white blood cells and of its changes with malignancy and cell culture. This enzyme might represent a useful marker in the characterization of the leukemic cells."} {"id": "PMID:156572", "title": "A study of arterial prostheses by scanning electron microscopy.", "content": "Scanning electron micrographs were taken of ten different vascular prostheses. The micrographs showed that some prostheses were damaged and some had traces of chemicals on their surface. The application of standard vascular clamps damaged most grafts and some showed remarkable changes on resterilization.", "contents": "A study of arterial prostheses by scanning electron microscopy. Scanning electron micrographs were taken of ten different vascular prostheses. The micrographs showed that some prostheses were damaged and some had traces of chemicals on their surface. The application of standard vascular clamps damaged most grafts and some showed remarkable changes on resterilization."} {"id": "PMID:156574", "title": "Serotonergic facilitation of facial motoneuron excitation.", "content": "The effect of serotonin (5-HT) on motoneurons located in the facial nucleus of the rat was investigated in the present study. Microiontophoretic application of 10--200 nA pulses of 5-HT lasting from 1 to 10 min failed to excite facial motoneurons. However, small amounts of 5-HT facilitated the subthreshold and threshold excitatory effects of iontophoretically applied glutamate on these cells. Typically, the current of glutamate required to produce an activation of facial motoneurons was reduced by at least 50% in the presence of 5-HT. In addition, 5-HT markedly shifted to the left the cumulative dose-response curve of glutamate-induced excitation of motoneurons. The 5-HT releasing agent p-chloroamphetamine (PCA) facilitated the excitatory effects of glutamate on montoneurons in control animals, but not in those pretreated with the 5-HT also facilitated the subthreshold and threshold excitation of motoneurons produced by stimulation of the motor cortex and the red nucleus. The facilitating effect of 5-HT was blocked by methysergide. Norepinephrine also facilitated facial motoneuron excitation but this effect was not blocked by methysergide. It is concluded that 5-HT in the facial nucleus functions in a manner that is not analagous to direct excitation, but rather acts as a gain setter to enhance the effects of excitatory afferent inputs.", "contents": "Serotonergic facilitation of facial motoneuron excitation. The effect of serotonin (5-HT) on motoneurons located in the facial nucleus of the rat was investigated in the present study. Microiontophoretic application of 10--200 nA pulses of 5-HT lasting from 1 to 10 min failed to excite facial motoneurons. However, small amounts of 5-HT facilitated the subthreshold and threshold excitatory effects of iontophoretically applied glutamate on these cells. Typically, the current of glutamate required to produce an activation of facial motoneurons was reduced by at least 50% in the presence of 5-HT. In addition, 5-HT markedly shifted to the left the cumulative dose-response curve of glutamate-induced excitation of motoneurons. The 5-HT releasing agent p-chloroamphetamine (PCA) facilitated the excitatory effects of glutamate on montoneurons in control animals, but not in those pretreated with the 5-HT also facilitated the subthreshold and threshold excitation of motoneurons produced by stimulation of the motor cortex and the red nucleus. The facilitating effect of 5-HT was blocked by methysergide. Norepinephrine also facilitated facial motoneuron excitation but this effect was not blocked by methysergide. It is concluded that 5-HT in the facial nucleus functions in a manner that is not analagous to direct excitation, but rather acts as a gain setter to enhance the effects of excitatory afferent inputs."} {"id": "PMID:156576", "title": "Interaction of sodium with the sarcolemmal calcium system.", "content": "Sarcolemma isolated from guinea pig heart binds calcium in an ATP-dependent manner. Sodium ions decrease the total amount of calcium bound by the membranes. ATP-dependent calcium binding is more sensitive to sodium than the non-ATP-dependent calcium binding. The ATPase active during calcium binding is affected by sodium ions to the same extent as the ATP-dependent calcium binding process. The inhibition of the calcium binding process and of ATPase activity by sodium was more pronounced when the membranes were preincubated with sodium. The effect of sodium on calcium binding is dependent on both the time of contact between sodium and the membranes and the concentration of sodium. It is suggested that the effect of sodium on the calcium binding system in the sarcolemma may be a link between the inhibition of Na+K+-ATPase (EC 3.6.1.3) by cardiac glycosides and the subsequent increase in intracellular calcium.", "contents": "Interaction of sodium with the sarcolemmal calcium system. Sarcolemma isolated from guinea pig heart binds calcium in an ATP-dependent manner. Sodium ions decrease the total amount of calcium bound by the membranes. ATP-dependent calcium binding is more sensitive to sodium than the non-ATP-dependent calcium binding. The ATPase active during calcium binding is affected by sodium ions to the same extent as the ATP-dependent calcium binding process. The inhibition of the calcium binding process and of ATPase activity by sodium was more pronounced when the membranes were preincubated with sodium. The effect of sodium on calcium binding is dependent on both the time of contact between sodium and the membranes and the concentration of sodium. It is suggested that the effect of sodium on the calcium binding system in the sarcolemma may be a link between the inhibition of Na+K+-ATPase (EC 3.6.1.3) by cardiac glycosides and the subsequent increase in intracellular calcium."} {"id": "PMID:156577", "title": "The biosynthesis of the free sterols and sterol esters of Neurospora crassa.", "content": "The composition of the free and esterified sterols in Neurospora crassa was examined as a function of incubation time in starvation medium containing [2-14C]mevalonic acid. The 14C incorporation was monitored in nuclear methylated and 4,14-desmethyl sterol fractions. After 7 h incubation, sterol esterification had increased from an initial 5% in the log phase culture to 48% of the total sterol pool, with a concomitant decrease in free sterols. The relationship of the free and esterified sterol components in ergosterol biosynthesis is discussed.", "contents": "The biosynthesis of the free sterols and sterol esters of Neurospora crassa. The composition of the free and esterified sterols in Neurospora crassa was examined as a function of incubation time in starvation medium containing [2-14C]mevalonic acid. The 14C incorporation was monitored in nuclear methylated and 4,14-desmethyl sterol fractions. After 7 h incubation, sterol esterification had increased from an initial 5% in the log phase culture to 48% of the total sterol pool, with a concomitant decrease in free sterols. The relationship of the free and esterified sterol components in ergosterol biosynthesis is discussed."} {"id": "PMID:156578", "title": "Cardiac output measurement by thermodilution.", "content": "The accuracy of thermodilution for measuring cardiac output was studied by comparing this method with measurements obtained by an electromagnetic flowmeter in the dog. Thermal curves were computed by a cardiac output computer and absolute flows were obtained by pump calibration of the flowmeter. Regression analysis showed an excellent correlation (P less than 0.001) between thermodilution measurements with injectates at 0 degrees C and flowmeter measurements using either cannulating probes (n = 105, r = 0.98) or periaortic probes (n = 100, r = 0.96). With the use of normal room temperature injectates, a good correlation was also found with absolute flows (n = 75, r = 0.92, P less than 0.001). Thermodilution overestimated cardiac output by 3% to 9%. In 32 pairs of successive cardiac output determinations by thermodilution, there was no significant difference between the two measurements (P greater than 0.05). In eight patients cardiac output was measured postoperatively by thermodilution with injectates at 0 degrees C and 24 degrees C administered in rapid succession. Regression analysis of 50 pairs of measurements at the two temperatures showed a strong correlation between the two techniques (r = 0.96) and the two results were not significantly different (P = 0.00001).", "contents": "Cardiac output measurement by thermodilution. The accuracy of thermodilution for measuring cardiac output was studied by comparing this method with measurements obtained by an electromagnetic flowmeter in the dog. Thermal curves were computed by a cardiac output computer and absolute flows were obtained by pump calibration of the flowmeter. Regression analysis showed an excellent correlation (P less than 0.001) between thermodilution measurements with injectates at 0 degrees C and flowmeter measurements using either cannulating probes (n = 105, r = 0.98) or periaortic probes (n = 100, r = 0.96). With the use of normal room temperature injectates, a good correlation was also found with absolute flows (n = 75, r = 0.92, P less than 0.001). Thermodilution overestimated cardiac output by 3% to 9%. In 32 pairs of successive cardiac output determinations by thermodilution, there was no significant difference between the two measurements (P greater than 0.05). In eight patients cardiac output was measured postoperatively by thermodilution with injectates at 0 degrees C and 24 degrees C administered in rapid succession. Regression analysis of 50 pairs of measurements at the two temperatures showed a strong correlation between the two techniques (r = 0.96) and the two results were not significantly different (P = 0.00001)."} {"id": "PMID:156579", "title": "Guidelines to birth control counselling of the physically handicapped.", "content": "Birth control counselling of well motivated physically handicapped men and women is discussed in a series of suggested steps: (1) preappointment arrangements are made to ensure physical access to the office, and the partner or a helper may be invited to the visit; (2) the patient is encouraged to name the desired birth control method; (3) the patient's fertility is established from the history and the results of physical examination and laboratory tests; (4) methods of birth control are matched to the patient's physical and mental capabilities; (5) potential side effects of the proposed methods are considered in the light of the handicap; (6) a method is finally recommended that may be a trade-off, with ease of use balanced against efficacy, and living with side effects balanced against the risks of pregnancy; and (7) rechecks are necessary to ensure that the patient is using the method with skill and satisfaction.", "contents": "Guidelines to birth control counselling of the physically handicapped. Birth control counselling of well motivated physically handicapped men and women is discussed in a series of suggested steps: (1) preappointment arrangements are made to ensure physical access to the office, and the partner or a helper may be invited to the visit; (2) the patient is encouraged to name the desired birth control method; (3) the patient's fertility is established from the history and the results of physical examination and laboratory tests; (4) methods of birth control are matched to the patient's physical and mental capabilities; (5) potential side effects of the proposed methods are considered in the light of the handicap; (6) a method is finally recommended that may be a trade-off, with ease of use balanced against efficacy, and living with side effects balanced against the risks of pregnancy; and (7) rechecks are necessary to ensure that the patient is using the method with skill and satisfaction."} {"id": "PMID:156580", "title": "A phase I study of chlorozotocin (NSC 178248).", "content": "Chlorozotocin was administered by rapid intravenous infusion to 35 patients with advanced cancer on either single-day of five-consecutive-day schedules. Total doses per course ranged from 12.5 to 200 mg/m2. On either administration schedule, dose limiting toxicities were thrombocytopenia and leukopenia at total doses of 150 mg/m2 to 200 mg/m2. Repetitive courses of drug may produce progressive impairment of renal and bone marrow function. Nausea and vomiting were infrequent and mild without definite relationship to dose. Minor reversible nondose related increases in SGOT and in serum creatinine occurred at all doses on both schedules. The plasma half-life of intact N-nitroso groups averaged 9.5 minutes after rapid intravenous administration of doses up to 40 mg/m2 and 12.5 minutes after doses of 150 or 200 mg/m2. No differences between plasma half-lives were seen between identical doses given on the first and fifth days of the five-day schedule. Objective tumor regression was noted in one patient with bronchogenic large cell carcinoma and one patient with metastatic melanoma.", "contents": "A phase I study of chlorozotocin (NSC 178248). Chlorozotocin was administered by rapid intravenous infusion to 35 patients with advanced cancer on either single-day of five-consecutive-day schedules. Total doses per course ranged from 12.5 to 200 mg/m2. On either administration schedule, dose limiting toxicities were thrombocytopenia and leukopenia at total doses of 150 mg/m2 to 200 mg/m2. Repetitive courses of drug may produce progressive impairment of renal and bone marrow function. Nausea and vomiting were infrequent and mild without definite relationship to dose. Minor reversible nondose related increases in SGOT and in serum creatinine occurred at all doses on both schedules. The plasma half-life of intact N-nitroso groups averaged 9.5 minutes after rapid intravenous administration of doses up to 40 mg/m2 and 12.5 minutes after doses of 150 or 200 mg/m2. No differences between plasma half-lives were seen between identical doses given on the first and fifth days of the five-day schedule. Objective tumor regression was noted in one patient with bronchogenic large cell carcinoma and one patient with metastatic melanoma."} {"id": "PMID:156581", "title": "Cultured human leukemic non-T/non-B lymphoblasts and their stimulating capacity in \"one-way\" mixed lymphocyte reaction: suggestive evidence for early T-cell or B-cell precursors.", "content": "It is now well recognized that a large proportion of cases with acute lymphoblastic leukemia are classified as non-T/non-B neoplastic disease. The origin of leukemic non-T/non-B cells is at present not known. It has been shown that fresh or cultured leukemic T lymphoblasts exert no stimulating capacity while leukemic B lymphoblasts exert a strong stimulation in \"one-way\" mixed lymphocyte reaction. It has also been shown that fresh leukemic cells from some patients with non-T/non-B acute lymphoblastic leukemia possess a strong stimulation while leukemic cells from other patients with this disease possess no stimulation on allogeneic lymphocytes. The present study shows that cultured leukemic lymphoblasts from 3 non-T/non-B cell lines (NALL-1, NALM-6 and NALM-16) consistently exert a strong stimulation on allogeneic lymphocytes. On the other hand, cultured leukemic lymphoblasts from 2 non-T/non-B cell lines (REH and KM-3) consistently fail to stimulate in \"one-way\" mixed lymphocyte reaction. Our data clearly support the speculation that leukemic non-T/non-B cells which possess the stimulating capacity may represent less differentiated leukemic B lymphoid cells (pre-B cells) and leukemic non-T/non-B cells which possess no stimulating capacity may represent less differentiated leukemic T lymphoid cells (per-T cells).", "contents": "Cultured human leukemic non-T/non-B lymphoblasts and their stimulating capacity in \"one-way\" mixed lymphocyte reaction: suggestive evidence for early T-cell or B-cell precursors. It is now well recognized that a large proportion of cases with acute lymphoblastic leukemia are classified as non-T/non-B neoplastic disease. The origin of leukemic non-T/non-B cells is at present not known. It has been shown that fresh or cultured leukemic T lymphoblasts exert no stimulating capacity while leukemic B lymphoblasts exert a strong stimulation in \"one-way\" mixed lymphocyte reaction. It has also been shown that fresh leukemic cells from some patients with non-T/non-B acute lymphoblastic leukemia possess a strong stimulation while leukemic cells from other patients with this disease possess no stimulation on allogeneic lymphocytes. The present study shows that cultured leukemic lymphoblasts from 3 non-T/non-B cell lines (NALL-1, NALM-6 and NALM-16) consistently exert a strong stimulation on allogeneic lymphocytes. On the other hand, cultured leukemic lymphoblasts from 2 non-T/non-B cell lines (REH and KM-3) consistently fail to stimulate in \"one-way\" mixed lymphocyte reaction. Our data clearly support the speculation that leukemic non-T/non-B cells which possess the stimulating capacity may represent less differentiated leukemic B lymphoid cells (pre-B cells) and leukemic non-T/non-B cells which possess no stimulating capacity may represent less differentiated leukemic T lymphoid cells (per-T cells)."} {"id": "PMID:156583", "title": "Histochemical and ultrastructural properties of myoid cells in the thymus of the frog.", "content": "Histochemical and ultrastructural properties of myoid cells in the thymus of the frog were investigated and compared with properties of skeletal muscle fibres. The histochemical reactions of phospholipids, phosphorylase, succinic dehydrogenase and adenosine triphosphatase activities in myoid cells were characterized by considerable variability. Individual myoid cells apparently possess different enzyme activities which correspond to different stages of development, maturity and degeneration of these cells. The mature mononucleated myoid cells have similar enzymatic properties to the fast muscle fibres of the frog. This finding has been extended by ultrastructural observations. Features, typical of fast muscle fibres of the frog, e.g. the presence of the M-line, straight and narrow Z-line and well developed triads were found in the majority of mature myoid cells.", "contents": "Histochemical and ultrastructural properties of myoid cells in the thymus of the frog. Histochemical and ultrastructural properties of myoid cells in the thymus of the frog were investigated and compared with properties of skeletal muscle fibres. The histochemical reactions of phospholipids, phosphorylase, succinic dehydrogenase and adenosine triphosphatase activities in myoid cells were characterized by considerable variability. Individual myoid cells apparently possess different enzyme activities which correspond to different stages of development, maturity and degeneration of these cells. The mature mononucleated myoid cells have similar enzymatic properties to the fast muscle fibres of the frog. This finding has been extended by ultrastructural observations. Features, typical of fast muscle fibres of the frog, e.g. the presence of the M-line, straight and narrow Z-line and well developed triads were found in the majority of mature myoid cells."} {"id": "PMID:156584", "title": "Split gene for mitochondrial 24S ribosomal RNA of Neurospora crassa.", "content": "The 60 kb circular mitochondrial genome of N. crassa has previously been shown to contain a single transcription unit for 17S and 24S rRNA mapping within the largest Eco RI fragment E1 (19.6 kb). This fragment was isolated from uncloned mitochondrial DNA and further analyzed by cleavage with restriction endonucleases Hind II, Hind III, Bam HI, Pvu II and BgI I, and by electron microscopy of rRNA/DNA hybrids. The resulting map shows a 2.3 kb intervening sequence interrupting the gene for 24S rRNA. The main part (2.7 kb) of this gene is separated from the 17S rRNA gene by a 5 kb segment which contains several transfer RNA genes. This segment is much longer than the putative 1 kb spacer sequence within the 32S precursor molecule for both rRNAs, suggesting a second splicing event in that region.", "contents": "Split gene for mitochondrial 24S ribosomal RNA of Neurospora crassa. The 60 kb circular mitochondrial genome of N. crassa has previously been shown to contain a single transcription unit for 17S and 24S rRNA mapping within the largest Eco RI fragment E1 (19.6 kb). This fragment was isolated from uncloned mitochondrial DNA and further analyzed by cleavage with restriction endonucleases Hind II, Hind III, Bam HI, Pvu II and BgI I, and by electron microscopy of rRNA/DNA hybrids. The resulting map shows a 2.3 kb intervening sequence interrupting the gene for 24S rRNA. The main part (2.7 kb) of this gene is separated from the 17S rRNA gene by a 5 kb segment which contains several transfer RNA genes. This segment is much longer than the putative 1 kb spacer sequence within the 32S precursor molecule for both rRNAs, suggesting a second splicing event in that region."} {"id": "PMID:156604", "title": "Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia.", "content": "Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine.", "contents": "Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia. Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine."} {"id": "PMID:156605", "title": "The influence of left ventricular late diastolic filling on the A wave of the left ventricular pressure trace.", "content": "To study the influence of left ventricular (LV) late diastolic filling on the A wave of the LV pressure, simultaneously recorded echocardiographic LV dimensions and high-fidelity LV pressure measurements were taken in 24 patients. Group 1 comprised eight patients without LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) less than or equal to 13 mm Hg. Group 2 comprised 16 patients with LVH secondary to aortic stenosis, idiopathic hypertrophic subaortic stenosis, or hypertension and increased LVEDP. Patients in group 2 had significantly thicker left ventricles, decreased mitral E-to-F slopes, and larger A waves in the LV pressure curve. On the basis of end-diastolic chamber stiffness, we divided group 2 into two populations: 12 patients (group 2A) with end-diastolic chamber stiffness similar to that in group 1, and four patients (group 2B) with markedly elevated end-diastolic chamber stiffness. Patients in group 2A had a larger atrial contribution to LV filling than those with markedly abnormal stiffness (group 2B). Therefore, in LVH an increased A wave in the LV pressure may be related to either elevated end-diastolic chamber stiffness or augmented left atrial volume transport.", "contents": "The influence of left ventricular late diastolic filling on the A wave of the left ventricular pressure trace. To study the influence of left ventricular (LV) late diastolic filling on the A wave of the LV pressure, simultaneously recorded echocardiographic LV dimensions and high-fidelity LV pressure measurements were taken in 24 patients. Group 1 comprised eight patients without LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) less than or equal to 13 mm Hg. Group 2 comprised 16 patients with LVH secondary to aortic stenosis, idiopathic hypertrophic subaortic stenosis, or hypertension and increased LVEDP. Patients in group 2 had significantly thicker left ventricles, decreased mitral E-to-F slopes, and larger A waves in the LV pressure curve. On the basis of end-diastolic chamber stiffness, we divided group 2 into two populations: 12 patients (group 2A) with end-diastolic chamber stiffness similar to that in group 1, and four patients (group 2B) with markedly elevated end-diastolic chamber stiffness. Patients in group 2A had a larger atrial contribution to LV filling than those with markedly abnormal stiffness (group 2B). Therefore, in LVH an increased A wave in the LV pressure may be related to either elevated end-diastolic chamber stiffness or augmented left atrial volume transport."} {"id": "PMID:156606", "title": "Exercise-induced ST elevation in patients without myocardial infarction.", "content": "A review of 6040 consecutive exercise tests yielded 106 patients without previous myocardial infarction (MI) who had exercise-induced ST elevation (greater than or equal to 0.5 mm in a 15-lead ECG system). In 46, ST elevation was correlated with left ventriculography and coronary angiography. Coronary artery disease (CAD) (greater than or equal to 70% narrowing) was detected in 40 of 46 patients: 12 patients had one-vessel disease, 13 had two-vessel disease, and 15 had three-vessel disease. Resting ventriculograms were normal in 36 of 40 patients. Of 21 patients with anterior (V1-V3) ST elevation, 86% had a left anterior descending (LAD) obstruction and 78% had obstruction proximal to the first diagonal branch. LAD disease occurred significantly more frequently than right and circumflex CAD. There was no anatomic correlation of three persons with lateral (leads V4--6, I or aVL) or 27 patients with inferior-posterior (leads II, III, aVF, Y or Z) exercise-induced ST elevation. Therefore, exercise-induced ST elevation is strongly correlated with CAD but not resting wall motion abnormalities. Further, anterior exercise-induced ST elevation in patients without a previous MI often predicts a significant proximal LAD obstruction.", "contents": "Exercise-induced ST elevation in patients without myocardial infarction. A review of 6040 consecutive exercise tests yielded 106 patients without previous myocardial infarction (MI) who had exercise-induced ST elevation (greater than or equal to 0.5 mm in a 15-lead ECG system). In 46, ST elevation was correlated with left ventriculography and coronary angiography. Coronary artery disease (CAD) (greater than or equal to 70% narrowing) was detected in 40 of 46 patients: 12 patients had one-vessel disease, 13 had two-vessel disease, and 15 had three-vessel disease. Resting ventriculograms were normal in 36 of 40 patients. Of 21 patients with anterior (V1-V3) ST elevation, 86% had a left anterior descending (LAD) obstruction and 78% had obstruction proximal to the first diagonal branch. LAD disease occurred significantly more frequently than right and circumflex CAD. There was no anatomic correlation of three persons with lateral (leads V4--6, I or aVL) or 27 patients with inferior-posterior (leads II, III, aVF, Y or Z) exercise-induced ST elevation. Therefore, exercise-induced ST elevation is strongly correlated with CAD but not resting wall motion abnormalities. Further, anterior exercise-induced ST elevation in patients without a previous MI often predicts a significant proximal LAD obstruction."} {"id": "PMID:156607", "title": "Noninvasive screening criteria for enhanced 4-year survival after aortocoronary bypass surgery.", "content": "Two thousand one men with coronary heart disease (CHD) who were enrolled in the Exercise Testing Registry of the Seattle Heart Watch had symptom-limited maximal exercise tests at the initial clinical examination and follow-up surveillance of subsequent mortality for 4.1 +/- 1.6 years. When subdivided into three mutually exclusive subgroups, 636 patients did not have exertional myocardial ischemia, left ventricular dysfunction or cardiomegaly; 885 without cardiomegaly had only exertional ischemia; 480 had left ventricular dysfunction by either cardiomegaly and/or two noninvasive exertional criteria, with or without exertional myocardial ischemia. Three hundred thirty-one men had aortocoronary bypass surgery, while 1670 remained unopened for at least 4 years. Only 34% of the operated patients who had left ventricular dysfunction, as defined, showed a marked improvement in 4-year survival rates (p less than 0.01). Differences in the annual CHD mortality rates in relation to surgical treatment in the other two groups were not statistically significant. Restricting the analysis to a subset of patients who had invasive studies did not alter the conclusion. Accordingly, we suggest the use of noninvasive criteria to aid preliminary screening of patients for invasive studies and surgical treatment.", "contents": "Noninvasive screening criteria for enhanced 4-year survival after aortocoronary bypass surgery. Two thousand one men with coronary heart disease (CHD) who were enrolled in the Exercise Testing Registry of the Seattle Heart Watch had symptom-limited maximal exercise tests at the initial clinical examination and follow-up surveillance of subsequent mortality for 4.1 +/- 1.6 years. When subdivided into three mutually exclusive subgroups, 636 patients did not have exertional myocardial ischemia, left ventricular dysfunction or cardiomegaly; 885 without cardiomegaly had only exertional ischemia; 480 had left ventricular dysfunction by either cardiomegaly and/or two noninvasive exertional criteria, with or without exertional myocardial ischemia. Three hundred thirty-one men had aortocoronary bypass surgery, while 1670 remained unopened for at least 4 years. Only 34% of the operated patients who had left ventricular dysfunction, as defined, showed a marked improvement in 4-year survival rates (p less than 0.01). Differences in the annual CHD mortality rates in relation to surgical treatment in the other two groups were not statistically significant. Restricting the analysis to a subset of patients who had invasive studies did not alter the conclusion. Accordingly, we suggest the use of noninvasive criteria to aid preliminary screening of patients for invasive studies and surgical treatment."} {"id": "PMID:156602", "title": "A parental perspective on the Honeylands Home Visiting Project for severely handicapped infants provided by three mothers of older handicapped children.", "content": "Three mothers of severely handicapped children, who had not attended Honeylands nor received any home visiting, were asked to attend and participate in the monthly group meetings for the second year of the three year project (Rayner 1978). They each then decided to visit a family with their home therapist. They comment on the responsibility undertaken by all parties to this work; parents, therapist and supportive team.", "contents": "A parental perspective on the Honeylands Home Visiting Project for severely handicapped infants provided by three mothers of older handicapped children. Three mothers of severely handicapped children, who had not attended Honeylands nor received any home visiting, were asked to attend and participate in the monthly group meetings for the second year of the three year project (Rayner 1978). They each then decided to visit a family with their home therapist. They comment on the responsibility undertaken by all parties to this work; parents, therapist and supportive team."} {"id": "PMID:156609", "title": "A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis.", "content": "1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients.", "contents": "A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis. 1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients."} {"id": "PMID:156610", "title": "Self indentified personality patterns of children with facial or orthopedic disfigurement.", "content": "This study compared personality characteristics of children with cleft lip and palate to another group of children with different observable physical impairment (orthopedic disability) and speech difficulties. It was hypothesized that different types of observable physical stigmata may result in different personality adaptations. Forty-five children from each of two groups (25 males and 20 females) were matched for sex, age, and intelligence. They were compared using the Missouri Children's Picture Series, a non-verbal personality test, on the following dimensions: Conformity, Masculinity/Femininity, Maturity, Agression, Inhibition, Activity Level Sleep Disturbance and Somatization. The results indicate that males with cleft lip and palate are significantly higher on Maturity and Inhibition while Orthopedically Disabled males are higher on Agression, Activity Level, and Somatization. Cleft lip and palate females are significantly higher on Maturity and Inhibition while Orthopedically Disabled females are higher on Masculinity. The results indicate differential personality adaptations in the two different types of observable physical impairments. Results are discussed in terms of their relationship to selected psychosocial variables.", "contents": "Self indentified personality patterns of children with facial or orthopedic disfigurement. This study compared personality characteristics of children with cleft lip and palate to another group of children with different observable physical impairment (orthopedic disability) and speech difficulties. It was hypothesized that different types of observable physical stigmata may result in different personality adaptations. Forty-five children from each of two groups (25 males and 20 females) were matched for sex, age, and intelligence. They were compared using the Missouri Children's Picture Series, a non-verbal personality test, on the following dimensions: Conformity, Masculinity/Femininity, Maturity, Agression, Inhibition, Activity Level Sleep Disturbance and Somatization. The results indicate that males with cleft lip and palate are significantly higher on Maturity and Inhibition while Orthopedically Disabled males are higher on Agression, Activity Level, and Somatization. Cleft lip and palate females are significantly higher on Maturity and Inhibition while Orthopedically Disabled females are higher on Masculinity. The results indicate differential personality adaptations in the two different types of observable physical impairments. Results are discussed in terms of their relationship to selected psychosocial variables."} {"id": "PMID:156614", "title": "Allergic contact dermatitis to isopropylaminodiphenylamine (IPPD).", "content": "Fifty-one patients allergic to IPPD have been reviewed and the clinical features and prognosis discussed. In 38 of the 51 patients, the dermatitis was considered as occupational, the majority being employed in the transport industry.", "contents": "Allergic contact dermatitis to isopropylaminodiphenylamine (IPPD). Fifty-one patients allergic to IPPD have been reviewed and the clinical features and prognosis discussed. In 38 of the 51 patients, the dermatitis was considered as occupational, the majority being employed in the transport industry."} {"id": "PMID:156615", "title": "Cyanoacrylate dermatitis.", "content": "An outbreak of irritant dermatitis from a cyanoacrylate glue among a group of electronic assembly workers is described. It was caused by vaporization of monomer under conditions of low relative humidity. No further outbreak occurred when the humidity of the working environment was raised above 55%.", "contents": "Cyanoacrylate dermatitis. An outbreak of irritant dermatitis from a cyanoacrylate glue among a group of electronic assembly workers is described. It was caused by vaporization of monomer under conditions of low relative humidity. No further outbreak occurred when the humidity of the working environment was raised above 55%."} {"id": "PMID:156616", "title": "Delayed irritation: hexanediol diacrylate and butanediol diacrylate.", "content": "Ephemeral topical contact with hexanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years' observation of 20 workers utilizing these substances in the electron beam coating department of a door factory, contact sensitization did not occur. The characteristics of delayed contact irritancy are enumerated. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis.", "contents": "Delayed irritation: hexanediol diacrylate and butanediol diacrylate. Ephemeral topical contact with hexanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years' observation of 20 workers utilizing these substances in the electron beam coating department of a door factory, contact sensitization did not occur. The characteristics of delayed contact irritancy are enumerated. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis."} {"id": "PMID:156626", "title": "Synergism of vitamins A and E with dermatologic applications.", "content": "A synergism between vitamins A and E has been demonstrated by a number of investigators, notably Stanley R. Ames, who showed that in rats on a vitamin E deficient diet, the serum vitamin A level remained low, no matter how much vitamin A was given by mouth, or even by injection, but that adding vitamin E to the diet restored the vitamin A serum level to normal. We have utilized these observations with a high degree of success where vitamin A alone had failed to control three dermatologic conditions involving a defect in keratinization, namely, keratosis follicularis (Darier's disease), pityriasis rubra pilaris, and acne vulgaris. It is possible that a number of additional dermatoses characterized by dyskeratosis or hyperkeratosis might also be benefited by this combination.", "contents": "Synergism of vitamins A and E with dermatologic applications. A synergism between vitamins A and E has been demonstrated by a number of investigators, notably Stanley R. Ames, who showed that in rats on a vitamin E deficient diet, the serum vitamin A level remained low, no matter how much vitamin A was given by mouth, or even by injection, but that adding vitamin E to the diet restored the vitamin A serum level to normal. We have utilized these observations with a high degree of success where vitamin A alone had failed to control three dermatologic conditions involving a defect in keratinization, namely, keratosis follicularis (Darier's disease), pityriasis rubra pilaris, and acne vulgaris. It is possible that a number of additional dermatoses characterized by dyskeratosis or hyperkeratosis might also be benefited by this combination."} {"id": "PMID:156627", "title": "Evaluation of abrasives in acne therapy.", "content": "Various abrasive materials, such as pumice, polyethylene, and aluminum oxide are widely used as adjuncts in the therapy of acne. The apparent rationale is that abrasion should unseat comedones and deter their formation. We assessed the efficacy of various abrasives and abradant pads. Varying degrees of peeling and erythema were produced, but there was no appreciable reduction of comedones. Aggravation was noted in some cases. Generally, the resorption of papules and pustules was enhanced.", "contents": "Evaluation of abrasives in acne therapy. Various abrasive materials, such as pumice, polyethylene, and aluminum oxide are widely used as adjuncts in the therapy of acne. The apparent rationale is that abrasion should unseat comedones and deter their formation. We assessed the efficacy of various abrasives and abradant pads. Varying degrees of peeling and erythema were produced, but there was no appreciable reduction of comedones. Aggravation was noted in some cases. Generally, the resorption of papules and pustules was enhanced."} {"id": "PMID:156629", "title": "Co-existing aortic stenosis and secondary hypertrophic cardiomyopathy manifested by an hourglass left ventricle. Successful treatment with verapamil.", "content": "A patient with moderate aortic stenosis had severe hypertrophy and a typical hourglass appearance of the left ventricle. His effort-induced angina and dyspnea responded to treatment with verapamil. We suggest that the aortic stenosis resulted in secondary hypertrophic cardiomyopathy which may be treated by calcium antagonists.", "contents": "Co-existing aortic stenosis and secondary hypertrophic cardiomyopathy manifested by an hourglass left ventricle. Successful treatment with verapamil. A patient with moderate aortic stenosis had severe hypertrophy and a typical hourglass appearance of the left ventricle. His effort-induced angina and dyspnea responded to treatment with verapamil. We suggest that the aortic stenosis resulted in secondary hypertrophic cardiomyopathy which may be treated by calcium antagonists."} {"id": "PMID:156630", "title": "Radiopharmaceutical bone scanning in pediatric neurosurgery.", "content": "Radionuclide bone scanning is an extremely sensitive, safe and widely applicable investigative aid. In most circumstances it cannot be employed to the exclusion of plain radiography as the two procedures--one dynamic and the other static--complement each other. In children, bone imaging demonstrates physiologic characteristics of bone growth and early suture closure, delineates obscure tumors and infection, recent or old trauma not always visible on orthodox radiography and may solve the diagnostic dilemma of a child with heretofore undiagnosed head, neck or back pain.", "contents": "Radiopharmaceutical bone scanning in pediatric neurosurgery. Radionuclide bone scanning is an extremely sensitive, safe and widely applicable investigative aid. In most circumstances it cannot be employed to the exclusion of plain radiography as the two procedures--one dynamic and the other static--complement each other. In children, bone imaging demonstrates physiologic characteristics of bone growth and early suture closure, delineates obscure tumors and infection, recent or old trauma not always visible on orthodox radiography and may solve the diagnostic dilemma of a child with heretofore undiagnosed head, neck or back pain."} {"id": "PMID:156631", "title": "[Subendocardial jeopardy of the hypertrophied myocardium].", "content": "In moderate hypertrophy (+35%) of the canine left ventricle (LV), resting myocardial blood flow (MBF, tracer microspheres) was not significantly altered when compared with controls. The endo/epi flow ratio of the LV was, however, significantly smaller (0.82-0.9) than in controls (1.02-1.17). After coronary dilatation with dipyridamole, coronary flow reserve was smaller in hypertrophied hearts. This became particularly obvious when acute coronary constriction (70%) was induced. There was, however, no indication that after coronary constriction in early hypertrophy the subendocardium was more jeopardized than in controls.", "contents": "[Subendocardial jeopardy of the hypertrophied myocardium]. In moderate hypertrophy (+35%) of the canine left ventricle (LV), resting myocardial blood flow (MBF, tracer microspheres) was not significantly altered when compared with controls. The endo/epi flow ratio of the LV was, however, significantly smaller (0.82-0.9) than in controls (1.02-1.17). After coronary dilatation with dipyridamole, coronary flow reserve was smaller in hypertrophied hearts. This became particularly obvious when acute coronary constriction (70%) was induced. There was, however, no indication that after coronary constriction in early hypertrophy the subendocardium was more jeopardized than in controls."} {"id": "PMID:156632", "title": "[Role of LD-antigens in allogenic swine liver transplantation].", "content": "The different distribution of SD and LD antigens in the liver after a pig liver allograft creates a state of anti-LD immunity. This anti-LD immunity alters the immune response of the recipient and leads to a spontaneous recovery of the liver allograft rejection.", "contents": "[Role of LD-antigens in allogenic swine liver transplantation]. The different distribution of SD and LD antigens in the liver after a pig liver allograft creates a state of anti-LD immunity. This anti-LD immunity alters the immune response of the recipient and leads to a spontaneous recovery of the liver allograft rejection."} {"id": "PMID:156636", "title": "[The contribution of laparoscopy to diagnosis of malignant lymphomas (author's transl)].", "content": "Peritoneoscopy revealed in 15 patients with malignant lymphomas splenomegaly (13 patients), hepatomegaly (10 patients, 8 of them with impressive or suspicious alterations of the liver surface) and enlargement of retroperitoneal lymph nodes or localised infiltration of a jejunal loop (3 patients). Aimed biopsy of liver, spleen or lymph nodes frequently established the diagnosis definitively. The various features of malignant lymphomas observable at peritoneoscopy are described. Based on these experiences peritoneoscopy is recommended in suspected malignant lymphomas as a real diagnostic aid.", "contents": "[The contribution of laparoscopy to diagnosis of malignant lymphomas (author's transl)]. Peritoneoscopy revealed in 15 patients with malignant lymphomas splenomegaly (13 patients), hepatomegaly (10 patients, 8 of them with impressive or suspicious alterations of the liver surface) and enlargement of retroperitoneal lymph nodes or localised infiltration of a jejunal loop (3 patients). Aimed biopsy of liver, spleen or lymph nodes frequently established the diagnosis definitively. The various features of malignant lymphomas observable at peritoneoscopy are described. Based on these experiences peritoneoscopy is recommended in suspected malignant lymphomas as a real diagnostic aid."} {"id": "PMID:156637", "title": "Monoaminergic control of episodic growth hormone secretion in the rat: effects of reserpine, alpha-methyl-p-tyrosine, p-chlorophenylalanine, and haloperidol.", "content": "The effects on GH secretion of reserpine, alpha-methyl-p-tyrosine (alpha-MT), p-chlorophenylalanine (PCPA), and haloperidol were studied in undisturbed, unanesthetized male rats with implanted intraaortic cannulae. The effects of the various drug treatments on motor activity and brain levels of catecholamines (CAs) and 5-hydroxytryptamine (5-HT) as well as the synthesis of the biogenic amines were also studied. Reserpine (10 mg/kg, ip) completely inhibited GH secretion for at least 15 h. Repeated injections of reserpine prolonged this inhibition. Episodic GH secretion reappeared 36 h after the last administration of reserpine, at which time the behavioral inhibition and blepharospasm induced by the drug was less pronounced than after 24 h, but brain levels of CAs and 5-HT were still markedly reduced. Administration of alpha-MT (150 mg/kg; 12, 4, and 2 h before experiments) inhibited episodic GH secretion and caused marked inhibition of motor activity and brain levels of CAs but not 5-HT. The inhibition of episodic GH secretion was more pronounced with haloperidol (0.5 mg/kg; 30 min before experiments) than with alpha-MT but was not as complete as that found 12 h after administration of reserpine. Administration of p-chlorophenylalanine (300 mg/kg; 72, 48, and 24 h before experiments) had no effect on episodic GH secretion, whereas brain levels of 5-HT and 5-HT synthesis were markedly reduced.", "contents": "Monoaminergic control of episodic growth hormone secretion in the rat: effects of reserpine, alpha-methyl-p-tyrosine, p-chlorophenylalanine, and haloperidol. The effects on GH secretion of reserpine, alpha-methyl-p-tyrosine (alpha-MT), p-chlorophenylalanine (PCPA), and haloperidol were studied in undisturbed, unanesthetized male rats with implanted intraaortic cannulae. The effects of the various drug treatments on motor activity and brain levels of catecholamines (CAs) and 5-hydroxytryptamine (5-HT) as well as the synthesis of the biogenic amines were also studied. Reserpine (10 mg/kg, ip) completely inhibited GH secretion for at least 15 h. Repeated injections of reserpine prolonged this inhibition. Episodic GH secretion reappeared 36 h after the last administration of reserpine, at which time the behavioral inhibition and blepharospasm induced by the drug was less pronounced than after 24 h, but brain levels of CAs and 5-HT were still markedly reduced. Administration of alpha-MT (150 mg/kg; 12, 4, and 2 h before experiments) inhibited episodic GH secretion and caused marked inhibition of motor activity and brain levels of CAs but not 5-HT. The inhibition of episodic GH secretion was more pronounced with haloperidol (0.5 mg/kg; 30 min before experiments) than with alpha-MT but was not as complete as that found 12 h after administration of reserpine. Administration of p-chlorophenylalanine (300 mg/kg; 72, 48, and 24 h before experiments) had no effect on episodic GH secretion, whereas brain levels of 5-HT and 5-HT synthesis were markedly reduced."} {"id": "PMID:156638", "title": "Enzymic profiles of bovine pancreatic ductal and acinar tissues.", "content": "The plasma membrane enzymes, alkaline phosphatase, bicarbonate-dependent adenosine triphosphatase, 5'-nucleotidase, and carbonate dehydratase, were measured in ductal and acinar preparations of bovine pancreas. Epithelial cells were scraped from the main duct and a piece of acinar tissue was dissected from the whole pancreas for homogenization. All enzymes studied demonstrated higher levels in the duct per milligram protein than in the acinus: bicarbonate-dependent adenosine triphosphatase was 2.8 times higher; 5'-nucleotidase, 4.1 times higher; carbonate dehydratase, 16.9 times higher, while alkaline phosphatase showed only a slight increase in the duct compared to acini.", "contents": "Enzymic profiles of bovine pancreatic ductal and acinar tissues. The plasma membrane enzymes, alkaline phosphatase, bicarbonate-dependent adenosine triphosphatase, 5'-nucleotidase, and carbonate dehydratase, were measured in ductal and acinar preparations of bovine pancreas. Epithelial cells were scraped from the main duct and a piece of acinar tissue was dissected from the whole pancreas for homogenization. All enzymes studied demonstrated higher levels in the duct per milligram protein than in the acinus: bicarbonate-dependent adenosine triphosphatase was 2.8 times higher; 5'-nucleotidase, 4.1 times higher; carbonate dehydratase, 16.9 times higher, while alkaline phosphatase showed only a slight increase in the duct compared to acini."} {"id": "PMID:156639", "title": "Effects of phospholipase A2 and albumin on the calcium-dependent ATPase and the lipid composition of sarcoplasmic membranes.", "content": "1. The calcium-dependent ATPase activity of phospholipase-A2-digested sarcoplasmic vesicles decreases concomitantly with the contents of residual lysophospholipids and fatty acids when increasing albumin concentrations are applied. 2. Delipidated albumin preferentially removes unsaturated fatty acids and lysophosphatidylcholine. A complete removal of the phospholipids by albumin does not occur. 3. The membrane-bound lysophospholipids were analysed with respect to type of phospholipid, plasmalogen content and fatty acid chains by means of thin-layer chromatography and gas chromatography. 4. While the fatty acid composition of the lysophospholipids is independent of the degree of delipidation, the composition of the residual free fatty acids is found to change with the albumin concentration. 5. Reactivation of the Ca2+-ATPase by oleate leads to reasonable activities at room temperature as long as a minimum of about 30 lysophospholipid molec-les per ATPase is left. The course of the residual Ca2+-ATPase activity with the degree of delipidation is related to the presence of unsaturated fatty acids. 6. No specific role of either sphingomyelin or the plasmalogens has been found.", "contents": "Effects of phospholipase A2 and albumin on the calcium-dependent ATPase and the lipid composition of sarcoplasmic membranes. 1. The calcium-dependent ATPase activity of phospholipase-A2-digested sarcoplasmic vesicles decreases concomitantly with the contents of residual lysophospholipids and fatty acids when increasing albumin concentrations are applied. 2. Delipidated albumin preferentially removes unsaturated fatty acids and lysophosphatidylcholine. A complete removal of the phospholipids by albumin does not occur. 3. The membrane-bound lysophospholipids were analysed with respect to type of phospholipid, plasmalogen content and fatty acid chains by means of thin-layer chromatography and gas chromatography. 4. While the fatty acid composition of the lysophospholipids is independent of the degree of delipidation, the composition of the residual free fatty acids is found to change with the albumin concentration. 5. Reactivation of the Ca2+-ATPase by oleate leads to reasonable activities at room temperature as long as a minimum of about 30 lysophospholipid molec-les per ATPase is left. The course of the residual Ca2+-ATPase activity with the degree of delipidation is related to the presence of unsaturated fatty acids. 6. No specific role of either sphingomyelin or the plasmalogens has been found."} {"id": "PMID:156641", "title": "Bronchodilator activity of dimaprit in the guinea pig in vitro and in vivo.", "content": "The bronchodilator activity of the H2-recptor agonist, dimaprit, was assessed in vitro and in vivo. In vitro dimaprit relaxed guinea pig tracheal spirals and parenchymal strips that were constricted by the H1 receptor agonist, 2-PEA, or by carbachol. The H2-receptor antagonist, metiamide, inhibited this effect of dimaprit in vitro on both tissues constricted by 2-PEA but not on the carbachol constricted tracheal spiral. Intravenous infusion of dimaprit in the intact guinea pig resulted in reversal of bronchoconstriction induced by subcutaneous injection of 2-PEA. In vivo pretreatment with the H2-recptor antagonist, metiamide, resulted in a diminished sensitivity to the bronchodilating effects of intravenous dimaprit.", "contents": "Bronchodilator activity of dimaprit in the guinea pig in vitro and in vivo. The bronchodilator activity of the H2-recptor agonist, dimaprit, was assessed in vitro and in vivo. In vitro dimaprit relaxed guinea pig tracheal spirals and parenchymal strips that were constricted by the H1 receptor agonist, 2-PEA, or by carbachol. The H2-receptor antagonist, metiamide, inhibited this effect of dimaprit in vitro on both tissues constricted by 2-PEA but not on the carbachol constricted tracheal spiral. Intravenous infusion of dimaprit in the intact guinea pig resulted in reversal of bronchoconstriction induced by subcutaneous injection of 2-PEA. In vivo pretreatment with the H2-recptor antagonist, metiamide, resulted in a diminished sensitivity to the bronchodilating effects of intravenous dimaprit."} {"id": "PMID:156649", "title": "Some effects of an intrauterine device on glucosaminoglycans of the hamster uterus.", "content": "The effect of an intrauterine device (IUD) on non-heparin sulfomucopolysaccharide (SMP) was studied in castrated, hormone-treated, and cycling hamsters by photographic densitometry of tissue sections stained specifically for SMP with Alcian blue. Non-heparin SMP increased slightly in the myometrium of IUD-containing uteri of all castrated groups, with the increase being significant in only the peanut oil-treated group. The endometrium also showed slight increases in sulfomucin in IUD-containing uteri of peanut oil, progesterone, and estrogen plus progesterone-treated animals. These increases, however, were not statistically significant. In cycling hamsters the IUD had little effect on uterine non-heparin SMP in most cycle stages.", "contents": "Some effects of an intrauterine device on glucosaminoglycans of the hamster uterus. The effect of an intrauterine device (IUD) on non-heparin sulfomucopolysaccharide (SMP) was studied in castrated, hormone-treated, and cycling hamsters by photographic densitometry of tissue sections stained specifically for SMP with Alcian blue. Non-heparin SMP increased slightly in the myometrium of IUD-containing uteri of all castrated groups, with the increase being significant in only the peanut oil-treated group. The endometrium also showed slight increases in sulfomucin in IUD-containing uteri of peanut oil, progesterone, and estrogen plus progesterone-treated animals. These increases, however, were not statistically significant. In cycling hamsters the IUD had little effect on uterine non-heparin SMP in most cycle stages."} {"id": "PMID:156650", "title": "Early assessment of a tubal plastic (Bleier) clip.", "content": "Fifty patients have been sterilized laparoscopically using a plastic tubal (Bleier) clip having a \"snap-shut\" mechanism. Initial assessment indicates that the method is simple in principle but there are limitations, including the bulky dimensions of the applicator, absence of a safety-catch mechanism, and faults in the clip design. Modifications are indicated before further evaluation.", "contents": "Early assessment of a tubal plastic (Bleier) clip. Fifty patients have been sterilized laparoscopically using a plastic tubal (Bleier) clip having a \"snap-shut\" mechanism. Initial assessment indicates that the method is simple in principle but there are limitations, including the bulky dimensions of the applicator, absence of a safety-catch mechanism, and faults in the clip design. Modifications are indicated before further evaluation."} {"id": "PMID:156653", "title": "[Effect of noradrenaline on ion and water transport through frog gall bladder epithelium].", "content": "In experiments on isolated gallbladders (GB) of frogs it was established that noradrenaline in concentration of 6.10(-9)--3.10(-4) M acting on the organ from the serosalsurface causes firstly a short increase and then -- a prolonged inhibition of the absorption rate of NaCl -- isotonic fluid from the gall bladder cavity. While the concentration of the mediator increases in the inculation medium, its inhibiting effect increases too. Depression, and at high concentration in the medium, full inhibition of the process of fluid absorption is accompanied with distinct decrease of Na--, K--ATPase activity of gall bladder epithelial cells. Mediator in concentration of 3.10(-8) M caused an increase of membrane potential of the epithelial cells, while its increasing in the inculation medium to 3.10(-6) M caused a decrease of the transmembrane potential difference. Under the noradrenaline influence the increase of the osmotic permeability of the gall bladder's wall for the water flow directed from the mucosa to the serosalsurface of the organ took place, and also the decrease of the wall's permeability for the water flow in the opposite direction was seen. It was concluded that the noradrenaline inhibitory action on the process of absorption of NaCl--isotonic fluid from the gall bladder cavity was observed because of the decrease of the Na--K--ATPase activity, and also because of the change of the permeability of epithelium for the passive ion and water transport.", "contents": "[Effect of noradrenaline on ion and water transport through frog gall bladder epithelium]. In experiments on isolated gallbladders (GB) of frogs it was established that noradrenaline in concentration of 6.10(-9)--3.10(-4) M acting on the organ from the serosalsurface causes firstly a short increase and then -- a prolonged inhibition of the absorption rate of NaCl -- isotonic fluid from the gall bladder cavity. While the concentration of the mediator increases in the inculation medium, its inhibiting effect increases too. Depression, and at high concentration in the medium, full inhibition of the process of fluid absorption is accompanied with distinct decrease of Na--, K--ATPase activity of gall bladder epithelial cells. Mediator in concentration of 3.10(-8) M caused an increase of membrane potential of the epithelial cells, while its increasing in the inculation medium to 3.10(-6) M caused a decrease of the transmembrane potential difference. Under the noradrenaline influence the increase of the osmotic permeability of the gall bladder's wall for the water flow directed from the mucosa to the serosalsurface of the organ took place, and also the decrease of the wall's permeability for the water flow in the opposite direction was seen. It was concluded that the noradrenaline inhibitory action on the process of absorption of NaCl--isotonic fluid from the gall bladder cavity was observed because of the decrease of the Na--K--ATPase activity, and also because of the change of the permeability of epithelium for the passive ion and water transport."} {"id": "PMID:156655", "title": "[Spontaneous discharges of muscle receptors of different functional types].", "content": "Characteristics of discharges as well as presence or absence of spontaneous impulse activity (SIA) were studied in 473 receptors of deafferented muscles in anesthetized cats. The SIA was absent in majority of Golgi's organs, pressor receptors, and in elementary dynamic and static receptors of muscle spindles. The SIA probability is particularly high in spindle receptors of phasic-tonic type. Absence or presence of the SIA is one of criteria for identifying the type of receptors. Among the universal receptors of dynamic and position types, the SIA probability increases along with enhancement of the static response. The soleus muscle possesses a lesser amount of units with SIA than the m. triceps. Absence or presence of the SIA seem to depend on different ways of connection between sensitive terminals and the intrafusal fibers of the spindles which have been initially stretched in a relaxed muscle.", "contents": "[Spontaneous discharges of muscle receptors of different functional types]. Characteristics of discharges as well as presence or absence of spontaneous impulse activity (SIA) were studied in 473 receptors of deafferented muscles in anesthetized cats. The SIA was absent in majority of Golgi's organs, pressor receptors, and in elementary dynamic and static receptors of muscle spindles. The SIA probability is particularly high in spindle receptors of phasic-tonic type. Absence or presence of the SIA is one of criteria for identifying the type of receptors. Among the universal receptors of dynamic and position types, the SIA probability increases along with enhancement of the static response. The soleus muscle possesses a lesser amount of units with SIA than the m. triceps. Absence or presence of the SIA seem to depend on different ways of connection between sensitive terminals and the intrafusal fibers of the spindles which have been initially stretched in a relaxed muscle."} {"id": "PMID:156656", "title": "Lymph node activation by a factor released from lymphocytes of normal mice in reaction with Mycobacterium kansasii.", "content": "Substances which have the same properties as the previously described lymph node activating factor are released from the 4-h culture of 10 X 10(6) lymph node cells from normal non-sensitized mice and 2.5--5 X 10(6) Mycobacterium kansasii cells. They increase the number of lymphocytes with nucleoli synthesizing ribonucleic acid in the popliteal lymph nodes of intact mice and give the precipitation lines with the beta- to alpha-globulin electrophoretic mobility, which are specific for the lymph node activating factor, in reaction with serum against the supernatants from mixed lymphocyte cultures. The conclusion drawn from these observations is that the release of the factor or related substances is one of the more general manifestations of the early response of lymphocytes to foreign cells. The activating and in immunoelectrophoresis specifically reacting substance is not released from lymphocytes of mice from a specific pathogen-free colony. We assume that the release of the factor is not the primary reaction of the non-sensitized lymphocytes but the secondary reaction of lymphocytes presensitized with substances which share antigenic determinants with Mycobacteria.", "contents": "Lymph node activation by a factor released from lymphocytes of normal mice in reaction with Mycobacterium kansasii. Substances which have the same properties as the previously described lymph node activating factor are released from the 4-h culture of 10 X 10(6) lymph node cells from normal non-sensitized mice and 2.5--5 X 10(6) Mycobacterium kansasii cells. They increase the number of lymphocytes with nucleoli synthesizing ribonucleic acid in the popliteal lymph nodes of intact mice and give the precipitation lines with the beta- to alpha-globulin electrophoretic mobility, which are specific for the lymph node activating factor, in reaction with serum against the supernatants from mixed lymphocyte cultures. The conclusion drawn from these observations is that the release of the factor or related substances is one of the more general manifestations of the early response of lymphocytes to foreign cells. The activating and in immunoelectrophoresis specifically reacting substance is not released from lymphocytes of mice from a specific pathogen-free colony. We assume that the release of the factor is not the primary reaction of the non-sensitized lymphocytes but the secondary reaction of lymphocytes presensitized with substances which share antigenic determinants with Mycobacteria."} {"id": "PMID:156659", "title": "Gold salt-induced cholestasis.", "content": "The authors report the case of a patient with transient intrahepatic cholestasis following the administration of a soluble gold salt, sodium aurothiopropanol sulfonate. Other manifestations of intolerance to gold salts included exfoliative dermatitis and eosinophilia.", "contents": "Gold salt-induced cholestasis. The authors report the case of a patient with transient intrahepatic cholestasis following the administration of a soluble gold salt, sodium aurothiopropanol sulfonate. Other manifestations of intolerance to gold salts included exfoliative dermatitis and eosinophilia."} {"id": "PMID:156660", "title": "Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment.", "content": "Glomerular basement membrane thickness (GBMT) has been measured in streptozotocin diabetic rats treated with insulin. The study included 3 groups of 8 rats each: 1) a 'well-controlled' group of diabetic rats under insulin treatment with a plasma glucose level reasonable close to normal values, 2) a 'poorly-controlled' group also under insulin treatment with constant high plasma glucose values, and 3) an age and weight matched non-diabetic control group. After 6 months of diabetes, GBMT was measured applying an intercept method on 3 glomerular cross sections from each of the 24 animals. The measurements showed that mean GBMT was 132.2. nm in the non-diabetic control rats and 131.6 nm in the 'well-controlled' diabetic rats. In the 'poorly-controlled' group the man GBMT was 140.4 nm, i.e. statistically significant increased when compared to each of the two other groups, 2p = 0.022 and 0.012 respectively. The results demonstrate that good blood glucose control in rats preserves normal GBMT.", "contents": "Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Glomerular basement membrane thickness (GBMT) has been measured in streptozotocin diabetic rats treated with insulin. The study included 3 groups of 8 rats each: 1) a 'well-controlled' group of diabetic rats under insulin treatment with a plasma glucose level reasonable close to normal values, 2) a 'poorly-controlled' group also under insulin treatment with constant high plasma glucose values, and 3) an age and weight matched non-diabetic control group. After 6 months of diabetes, GBMT was measured applying an intercept method on 3 glomerular cross sections from each of the 24 animals. The measurements showed that mean GBMT was 132.2. nm in the non-diabetic control rats and 131.6 nm in the 'well-controlled' diabetic rats. In the 'poorly-controlled' group the man GBMT was 140.4 nm, i.e. statistically significant increased when compared to each of the two other groups, 2p = 0.022 and 0.012 respectively. The results demonstrate that good blood glucose control in rats preserves normal GBMT."} {"id": "PMID:156662", "title": "[Atrioventricular canal associated with Fallot's tetralogy. Anatomo-clinical study of 2 cases].", "content": "The Authors are examing two cases of A-V canal associated with T. of Fallot. The most important clinical aspects of this rare cardiopathy result in the following: -- the frequent coexistence with Down dyndrome; -- the ECG and VCG aspects of counterclockwise rotation of the initial vectors of QRS in the frontal plane; -- the simultaneous observation of the typical echocardiographical aspects of both kinds of cardiopathy. The injection of dye into both ventricles allows the precise diagnosis. The post-mortem study in both cases shows the morphology of A-V canal associated with the one of T. of Fallot. From the surgical point of view it is important to take into account the abnormal morphology and extension of VSD. The importance of the part that the conal cushion plays in the morphogenesis of the malformation is discussed.", "contents": "[Atrioventricular canal associated with Fallot's tetralogy. Anatomo-clinical study of 2 cases]. The Authors are examing two cases of A-V canal associated with T. of Fallot. The most important clinical aspects of this rare cardiopathy result in the following: -- the frequent coexistence with Down dyndrome; -- the ECG and VCG aspects of counterclockwise rotation of the initial vectors of QRS in the frontal plane; -- the simultaneous observation of the typical echocardiographical aspects of both kinds of cardiopathy. The injection of dye into both ventricles allows the precise diagnosis. The post-mortem study in both cases shows the morphology of A-V canal associated with the one of T. of Fallot. From the surgical point of view it is important to take into account the abnormal morphology and extension of VSD. The importance of the part that the conal cushion plays in the morphogenesis of the malformation is discussed."} {"id": "PMID:156665", "title": "[Laparoscopic sterilization with electrocautery: complications and reliability (author's transl)].", "content": "1084 laparoscopic sterilizations were evaluated in a retrospective study at the Universit\u00e4ts-Frauenklinik Z\u00fcrich. The operative and early postoperative complications and the reliability of the method were analysed and compared to the results in the literature. Based on a cumulative statistical analysis 0,5% intraoperative complications required laparotomy, the main indications being haemorrhages and bowel injuries. Failed attempts were encountered in one of 150 patients, the main causes of which were adhaesions and difficulties at establishing pneumoperitoneum. The failure rate of the laparoscopic electrocoagulation of the fallopian tube after a long-term follow-up was about 0,5%, 20--25% of these were ectopic pregnancies. The transection of the fallopian tubes did not diminish the pregnancy rate, but the risk of bleeding was considerably higher with this technic. Concurrently performed therapeutic abortion or preceeeding laparotomy did not increase the operative complication rate.", "contents": "[Laparoscopic sterilization with electrocautery: complications and reliability (author's transl)]. 1084 laparoscopic sterilizations were evaluated in a retrospective study at the Universit\u00e4ts-Frauenklinik Z\u00fcrich. The operative and early postoperative complications and the reliability of the method were analysed and compared to the results in the literature. Based on a cumulative statistical analysis 0,5% intraoperative complications required laparotomy, the main indications being haemorrhages and bowel injuries. Failed attempts were encountered in one of 150 patients, the main causes of which were adhaesions and difficulties at establishing pneumoperitoneum. The failure rate of the laparoscopic electrocoagulation of the fallopian tube after a long-term follow-up was about 0,5%, 20--25% of these were ectopic pregnancies. The transection of the fallopian tubes did not diminish the pregnancy rate, but the risk of bleeding was considerably higher with this technic. Concurrently performed therapeutic abortion or preceeeding laparotomy did not increase the operative complication rate."} {"id": "PMID:156667", "title": "[Population genetics of the population of the northern European RSFSR. III. Demographic and genetic characteristics of two rural communities of the Pinezhskii District of the Arkhangel'sk Region].", "content": "The paper deals with the distribution of genetic markers (systems ABO, Rh, Hp, PTC) and a number of phenotyping traits (folding of arms, hand clasping, tongue rolling, right- and left-handedness, the type of ear lobe, the types of dermatoglyphics patterns) in the inhabitants of 5 villages in the Pinezhsky district of the Arkhangelsky region of the RSFSR. The data presented in this work were obtained in the course of examination of over 900 persons. Among the systems analysed there was a statistically significant deviation from Hardy-Weinberg's equlibrium. It took place in two the least villages. In one case--for ABO blood groups, in another--for Hp system. There are an interesting fact of the excess of heterozygotes 2-1 and some excess of the group 0. Statistically significant differences between villages were shown for four genetic systems. Data on migrations, distribution of gene frequencies and estimated genetic and phenotype distances between villages of the same village community and between two communities suggest, that each village community can be considered as separate subdivided population. Considering the uniformity of the environmental pressure in the region examined, the heterogeneity of the population studied is apparently associated with a random genetic drift.", "contents": "[Population genetics of the population of the northern European RSFSR. III. Demographic and genetic characteristics of two rural communities of the Pinezhskii District of the Arkhangel'sk Region]. The paper deals with the distribution of genetic markers (systems ABO, Rh, Hp, PTC) and a number of phenotyping traits (folding of arms, hand clasping, tongue rolling, right- and left-handedness, the type of ear lobe, the types of dermatoglyphics patterns) in the inhabitants of 5 villages in the Pinezhsky district of the Arkhangelsky region of the RSFSR. The data presented in this work were obtained in the course of examination of over 900 persons. Among the systems analysed there was a statistically significant deviation from Hardy-Weinberg's equlibrium. It took place in two the least villages. In one case--for ABO blood groups, in another--for Hp system. There are an interesting fact of the excess of heterozygotes 2-1 and some excess of the group 0. Statistically significant differences between villages were shown for four genetic systems. Data on migrations, distribution of gene frequencies and estimated genetic and phenotype distances between villages of the same village community and between two communities suggest, that each village community can be considered as separate subdivided population. Considering the uniformity of the environmental pressure in the region examined, the heterogeneity of the population studied is apparently associated with a random genetic drift."} {"id": "PMID:156670", "title": "[Cerebral degeneration in Down's syndrome].", "content": "Clinical and neuropathological findings of a 63-year-old male and a 25-year-old female with Down's syndrome are presented. Neuropathological examination of the older patient revealed intense features of Alzheimer's disease or senile dementia, including congophilic angiopathy and extensive mineral deposits in the globus pallidus and in the white matter of the cerebellum. In the hippocampus of the younger patient, plaque-like bodies and a few neurofibrillary tangles were found. From a survey of the cases hitherto reported in the literature it appears that among patients over 50 years of age it is common to encounter pathological features typical of Alzheimer's disease or senile dementia, that plaque-like bodies may occur in the second decade, neurofibrillary tangles in the third decade and a congophilic angiopathy in the fourth decade. The congophilic angiopathy is a frequent finding. Due to their high frequency, calcium or calciumlike deposits are regarded as important histopathological substrates of Down's syndrome. The clinical symptomatology of the long-surviving patients with Down's syndrome is that of a non-characteristic brain aging process and differs from that of the typical Alzheimer's disease. Organic dementia is not regularly found. Altogether, the anatomical findings in adult patients with Down's syndrome indicate a premature aging of the brain, which becomes more significant and widespread with increasing age.", "contents": "[Cerebral degeneration in Down's syndrome]. Clinical and neuropathological findings of a 63-year-old male and a 25-year-old female with Down's syndrome are presented. Neuropathological examination of the older patient revealed intense features of Alzheimer's disease or senile dementia, including congophilic angiopathy and extensive mineral deposits in the globus pallidus and in the white matter of the cerebellum. In the hippocampus of the younger patient, plaque-like bodies and a few neurofibrillary tangles were found. From a survey of the cases hitherto reported in the literature it appears that among patients over 50 years of age it is common to encounter pathological features typical of Alzheimer's disease or senile dementia, that plaque-like bodies may occur in the second decade, neurofibrillary tangles in the third decade and a congophilic angiopathy in the fourth decade. The congophilic angiopathy is a frequent finding. Due to their high frequency, calcium or calciumlike deposits are regarded as important histopathological substrates of Down's syndrome. The clinical symptomatology of the long-surviving patients with Down's syndrome is that of a non-characteristic brain aging process and differs from that of the typical Alzheimer's disease. Organic dementia is not regularly found. Altogether, the anatomical findings in adult patients with Down's syndrome indicate a premature aging of the brain, which becomes more significant and widespread with increasing age."} {"id": "PMID:156671", "title": "[Lymphangitis carcinomatosa of the lung in carcinoma of the prostate: frequency, radiological appearances and clinical significance (author's transl)].", "content": "Lung metastases from carcinoma of the prostate usually manifest themselves as radiologically diffuse lymphangitis carcinomatosa. Unlike the pathological findings, a radiological diagnosis is relatively uncommon. We have investigated this retrospectively in 230 patients; in 192, radiographs were available for study. In over 10% lung metastases were found, mostly in the form of lymphangitis carcinomatosa. In view of the bad prognostic significance and therapeutic implications of lymphangitis carcinomatosa, it is important to bear this in mind and to look for it radiologically.", "contents": "[Lymphangitis carcinomatosa of the lung in carcinoma of the prostate: frequency, radiological appearances and clinical significance (author's transl)]. Lung metastases from carcinoma of the prostate usually manifest themselves as radiologically diffuse lymphangitis carcinomatosa. Unlike the pathological findings, a radiological diagnosis is relatively uncommon. We have investigated this retrospectively in 230 patients; in 192, radiographs were available for study. In over 10% lung metastases were found, mostly in the form of lymphangitis carcinomatosa. In view of the bad prognostic significance and therapeutic implications of lymphangitis carcinomatosa, it is important to bear this in mind and to look for it radiologically."} {"id": "PMID:156672", "title": "[Computer tomographic demonstration of lymph node metastases from malignant testicular tumours. A comparison of lymphography and computer tomography (author's transl)].", "content": "Lymphography and computer tomography was performed on 64 patients with malignant testicular tumours in order to demonstrate lymph node metastases. In 60 patients it was possible to confirm the findings by surgery. In 43 patients there was agreement between the findings of the computer tomogram and the lymphogram. In 39 of these patients lymph node metastases had been demonstrated, in three there was a false negative and in one a false positive. Amongst the patients in whom there was a descrepancy between the two types of examination, the CT findings were confirmed histologically in twelve, and the lymphographic findings in nine. In 12.5% CT added significant additional information. Accuracy of lymphography was 73% and of computer tomography 80%. Specificity for each examination was 79%.", "contents": "[Computer tomographic demonstration of lymph node metastases from malignant testicular tumours. A comparison of lymphography and computer tomography (author's transl)]. Lymphography and computer tomography was performed on 64 patients with malignant testicular tumours in order to demonstrate lymph node metastases. In 60 patients it was possible to confirm the findings by surgery. In 43 patients there was agreement between the findings of the computer tomogram and the lymphogram. In 39 of these patients lymph node metastases had been demonstrated, in three there was a false negative and in one a false positive. Amongst the patients in whom there was a descrepancy between the two types of examination, the CT findings were confirmed histologically in twelve, and the lymphographic findings in nine. In 12.5% CT added significant additional information. Accuracy of lymphography was 73% and of computer tomography 80%. Specificity for each examination was 79%."} {"id": "PMID:156673", "title": "[Chondromalacia patellae--arthrographic observations on the genesis and diagnosis of cartilaginous damage (author's transl)].", "content": "Thanks to recent advances in arthrography, diagnosis of cartilaginous lesions has increasingly become a task of the radiologist. An accurate assessment of the cartilage of the femoropatellar joint can be established via double-contrast technique and so-called \"d\u00e9fil\u00e9\" projections, whereas the axial projection of the patella without contrast medium shows only secondary arthrotic changes of bone and is unsuitable for demonstrating early cartilaginous damage. The classification of dysplastic patellae into different types according to Wiberg and Baumgartl yields a statistical correlation with the frequency of chondromalacia, but does not give any conclusive evidence in individual cases. A special influence on joint mechanics and the development of chondromalacia patellae is exercised by a cartilaginous ridge of the medial patellar facette.", "contents": "[Chondromalacia patellae--arthrographic observations on the genesis and diagnosis of cartilaginous damage (author's transl)]. Thanks to recent advances in arthrography, diagnosis of cartilaginous lesions has increasingly become a task of the radiologist. An accurate assessment of the cartilage of the femoropatellar joint can be established via double-contrast technique and so-called \"d\u00e9fil\u00e9\" projections, whereas the axial projection of the patella without contrast medium shows only secondary arthrotic changes of bone and is unsuitable for demonstrating early cartilaginous damage. The classification of dysplastic patellae into different types according to Wiberg and Baumgartl yields a statistical correlation with the frequency of chondromalacia, but does not give any conclusive evidence in individual cases. A special influence on joint mechanics and the development of chondromalacia patellae is exercised by a cartilaginous ridge of the medial patellar facette."} {"id": "PMID:156674", "title": "[Paget's disease--manifestations in the vertebral colum. Computer tomographic investigations (author's transl)].", "content": "Computer tomography has been found to be of value in the study of deformities and narrowing of the spinal canal in 52 patients with Paget's disease of vertebral bodies. To a limited extent it can also be used for evaluating the intervertebral foramina. Deformities of the spinal canal were classified into three degrees of severity. The most severe changes were found in the lower thoracic region. The presence of neurological complications is an indication for CT studies.", "contents": "[Paget's disease--manifestations in the vertebral colum. Computer tomographic investigations (author's transl)]. Computer tomography has been found to be of value in the study of deformities and narrowing of the spinal canal in 52 patients with Paget's disease of vertebral bodies. To a limited extent it can also be used for evaluating the intervertebral foramina. Deformities of the spinal canal were classified into three degrees of severity. The most severe changes were found in the lower thoracic region. The presence of neurological complications is an indication for CT studies."} {"id": "PMID:156675", "title": "[Computer tomography of the sacroiliac joints (author's transl)].", "content": "Computer tomography, like conventional radiography, can demonstrate inflammatory, degenerative or reparative, traumatic and neoplastic lesions of the sacroiliac joints. In some cases computer tomography adds important information, for instance as regards soft tissue changes near the S.I. joints in the presence of neoplastic or posttraumatic lesions (tumour extension, hematoma). Computer tomography is also able to demonstrate minor disalignment of the sacro-iliac joints (so-called sacro-listhesis).", "contents": "[Computer tomography of the sacroiliac joints (author's transl)]. Computer tomography, like conventional radiography, can demonstrate inflammatory, degenerative or reparative, traumatic and neoplastic lesions of the sacroiliac joints. In some cases computer tomography adds important information, for instance as regards soft tissue changes near the S.I. joints in the presence of neoplastic or posttraumatic lesions (tumour extension, hematoma). Computer tomography is also able to demonstrate minor disalignment of the sacro-iliac joints (so-called sacro-listhesis)."} {"id": "PMID:156676", "title": "[The kinetics of contrast media in cerebral tumours (author's transl)].", "content": "The increase in density of cerebral tumours following intravenous injection of contrast media was measured by computer tomography and was evaluated quantitatively. The density increase of 158 tumours five minute after injection was between 0 and 29 CT units. There are considerable variations in density increase of various types of tumour, but the scatter is so wide as to preclude a diagnosis of tumour type. In 75 tumours repeated measurement of contrast changes were carried out for two hours following the injection. Again the variation differs with different types of tumour, but is not characteristic enough for exact clinical diagnosis. In 26 patients contrast concentrations were measured in the tumour and the blood and a pharmaco-kinetic compartmental analysis was carried out. In some tumours contrast changes can be explained by a single compartment model, whereas in others a two compartment model is necessary. Certain conclusions regarding the mechanism of contrast uptake can be reached.", "contents": "[The kinetics of contrast media in cerebral tumours (author's transl)]. The increase in density of cerebral tumours following intravenous injection of contrast media was measured by computer tomography and was evaluated quantitatively. The density increase of 158 tumours five minute after injection was between 0 and 29 CT units. There are considerable variations in density increase of various types of tumour, but the scatter is so wide as to preclude a diagnosis of tumour type. In 75 tumours repeated measurement of contrast changes were carried out for two hours following the injection. Again the variation differs with different types of tumour, but is not characteristic enough for exact clinical diagnosis. In 26 patients contrast concentrations were measured in the tumour and the blood and a pharmaco-kinetic compartmental analysis was carried out. In some tumours contrast changes can be explained by a single compartment model, whereas in others a two compartment model is necessary. Certain conclusions regarding the mechanism of contrast uptake can be reached."} {"id": "PMID:156677", "title": "[Image properties of computer tomography. III. Measurements on homogenous materials. Relationship of attenuation and scatter to various parameters (author's transl)].", "content": "The present paper investigates the variations due to various parameters on the image of homogeneous materials as obtained with the Somatom CT scanner. Sugar solutions were used with concentrations equivalent to the absorption values of soft tissues. Because of quantum noise, attentuation at various points is not uniform, but is distributed in a Gaussian manner round a mean value. Using the Evaluskop it was possible to determine the degree of scatter. It was shown that, with increasing density of the material, the scatter increased and that this can be reduced by subjecting the tomogram to a smoothing process. It was further shown how the scatter depends on various parameters, such as thickness and dose. The amount of scatter in a tomogram is important in determining the density gradation which can be a achieved.", "contents": "[Image properties of computer tomography. III. Measurements on homogenous materials. Relationship of attenuation and scatter to various parameters (author's transl)]. The present paper investigates the variations due to various parameters on the image of homogeneous materials as obtained with the Somatom CT scanner. Sugar solutions were used with concentrations equivalent to the absorption values of soft tissues. Because of quantum noise, attentuation at various points is not uniform, but is distributed in a Gaussian manner round a mean value. Using the Evaluskop it was possible to determine the degree of scatter. It was shown that, with increasing density of the material, the scatter increased and that this can be reduced by subjecting the tomogram to a smoothing process. It was further shown how the scatter depends on various parameters, such as thickness and dose. The amount of scatter in a tomogram is important in determining the density gradation which can be a achieved."} {"id": "PMID:156678", "title": "[A comparative diagnostic study of malignant lesions of the liver by infusion angiography and percutaneous transhepatic portography (author's transl)].", "content": "The diagnostic effectiveness of percutaneous transhepatic portography (PTP) was evaluated in 21 patients with primary and metastatic liver carcinoma, who also had infusion hepatic angiography. The findings at PTP were compared with unequivocal tumor changes demonstrated at infusion hepatic angiography in all cases. PTP revealed tumors in 14 of 21 cases. The location, size and number of the tumor(s) were decisive for their detectability at PTP. Solitary lesions smaller than 2 cm in the central parts of the liver escaped detection, whereas lesions larger than 7 cm in the left lobe and 6 cm in the right lobe were demonstrated in all cases. Multiple metastases of 1--2 cm were detected in most cases. Lesions smaller than 4 cm were better shown by the sinusoidal phase at PTP, where lesions larger than 5 cm were better delineated by the portal venous phase.", "contents": "[A comparative diagnostic study of malignant lesions of the liver by infusion angiography and percutaneous transhepatic portography (author's transl)]. The diagnostic effectiveness of percutaneous transhepatic portography (PTP) was evaluated in 21 patients with primary and metastatic liver carcinoma, who also had infusion hepatic angiography. The findings at PTP were compared with unequivocal tumor changes demonstrated at infusion hepatic angiography in all cases. PTP revealed tumors in 14 of 21 cases. The location, size and number of the tumor(s) were decisive for their detectability at PTP. Solitary lesions smaller than 2 cm in the central parts of the liver escaped detection, whereas lesions larger than 7 cm in the left lobe and 6 cm in the right lobe were demonstrated in all cases. Multiple metastases of 1--2 cm were detected in most cases. Lesions smaller than 4 cm were better shown by the sinusoidal phase at PTP, where lesions larger than 5 cm were better delineated by the portal venous phase."} {"id": "PMID:156679", "title": "[Nonsurgical production of intrahepatic portosystemic venous shunts in portal hypertension with the double lumen balloon catheter (author's transl)].", "content": "A nonsurgical production of intrahepatic shungs between the left portal and left hepatic vein was evaluated in twelve dogs with acute portal hypertension. Dilatation of the intrahepatic tract was achieved by means of a double lumen balloon catheter introduced into the portal system with the transjugular approach. The shunts proved to be effective in immediate reduction of increased portal pressure and no significant complications were encountered.", "contents": "[Nonsurgical production of intrahepatic portosystemic venous shunts in portal hypertension with the double lumen balloon catheter (author's transl)]. A nonsurgical production of intrahepatic shungs between the left portal and left hepatic vein was evaluated in twelve dogs with acute portal hypertension. Dilatation of the intrahepatic tract was achieved by means of a double lumen balloon catheter introduced into the portal system with the transjugular approach. The shunts proved to be effective in immediate reduction of increased portal pressure and no significant complications were encountered."} {"id": "PMID:156680", "title": "[Evaluation of hepato-biliary functional scintigraphy with 99mTc diethyle-IDA. Findings in normal livers (author's transl)].", "content": "Hepato-biliary functional scintigraphy was performed on 51 patients with normal livers after in the injection of 99mTc diethyle-IDA. The results were analysed according the morphological criteria (demonstration of the bile duct, intra-hepatic ducts, gall bladder and renal tract) and functional criteria (T max, half-time biliary excretion values, development of activity in the bile duct, in the gall bladder and in the gut). Demonstration of the bile duct and gall bladder was successful in all cases if the examination was carried out after an appropriate interval following food. 84.3% of patients showed a gall bladder excretary pattern of the tracer and 15.7% a gall bladder storage pattern. Correspondingly, bile appeared in the duodenum at 16.5 +/- 6.5 minutes (excretion) or 79.3 +/- 49.5 minutes (storage). The left hepatic duct was shown in 58.8%, the right hepatic duct in only 58.8%. Sixty minutes after the injection no activity could be determined in the bile ducts beyond the liver parenchyma. The gall bladder could be identified after 26.6 +/- 24.4 minutes, occasionally it was much later, up to 110 minutes. The liver function curve showed a Tmax level of 6.8 +/- 2.7 minutes and half value time of 15.8 +/- 6.7 minutes. At 5 minutes after injection the renal pelvis could be identified in 19.6%, but in no case was this still present beyond 15 minutes. Duodeno-gastric reflux was not demonstrated.", "contents": "[Evaluation of hepato-biliary functional scintigraphy with 99mTc diethyle-IDA. Findings in normal livers (author's transl)]. Hepato-biliary functional scintigraphy was performed on 51 patients with normal livers after in the injection of 99mTc diethyle-IDA. The results were analysed according the morphological criteria (demonstration of the bile duct, intra-hepatic ducts, gall bladder and renal tract) and functional criteria (T max, half-time biliary excretion values, development of activity in the bile duct, in the gall bladder and in the gut). Demonstration of the bile duct and gall bladder was successful in all cases if the examination was carried out after an appropriate interval following food. 84.3% of patients showed a gall bladder excretary pattern of the tracer and 15.7% a gall bladder storage pattern. Correspondingly, bile appeared in the duodenum at 16.5 +/- 6.5 minutes (excretion) or 79.3 +/- 49.5 minutes (storage). The left hepatic duct was shown in 58.8%, the right hepatic duct in only 58.8%. Sixty minutes after the injection no activity could be determined in the bile ducts beyond the liver parenchyma. The gall bladder could be identified after 26.6 +/- 24.4 minutes, occasionally it was much later, up to 110 minutes. The liver function curve showed a Tmax level of 6.8 +/- 2.7 minutes and half value time of 15.8 +/- 6.7 minutes. At 5 minutes after injection the renal pelvis could be identified in 19.6%, but in no case was this still present beyond 15 minutes. Duodeno-gastric reflux was not demonstrated."} {"id": "PMID:156681", "title": "[Clinical result of thyroid scintigraphy and iodine estimations using a fluorescent technique (author's transl)].", "content": "The new technique of quantitative fluorescent scintigraphy was used for determining the regional distribution and concentration of stable intrathyroid iodine (127 I) in 96 patients. Average iodine concentration in normal people (20 individuals) without thyroid enlargement living in the Bavarian iodine-deficiency area was 0.38 +/- 0.07 mg/g. In 32 patients with simple goitres it was significantly lower at 0.17 +/- 0.06 mg/g. With this technique it was possible to separate two types of hyperthyroidism amongst 21 patients: those with low iodine concentration in the thyroid (0.15 +/- 0.08 mg/g) and those with high iodine concentration (0.42 +/- 0.12 mg/g) after iodine administration. The iodine concentration in decompensated autonomous adenomas in twelve patients was usually low (0.12 +/- 0.12 mg/g). On the other hand iodine concentration was high in the paranodular tissues and could be demonstrated on the fluorescent scintigram. The quality of the scintigram using this technique for concentrations below 0.1 mg/g is inadequate. In this situation good imates can be obtained by radionucleid scintgrams. The situation is reversed by previous administration of iodine.", "contents": "[Clinical result of thyroid scintigraphy and iodine estimations using a fluorescent technique (author's transl)]. The new technique of quantitative fluorescent scintigraphy was used for determining the regional distribution and concentration of stable intrathyroid iodine (127 I) in 96 patients. Average iodine concentration in normal people (20 individuals) without thyroid enlargement living in the Bavarian iodine-deficiency area was 0.38 +/- 0.07 mg/g. In 32 patients with simple goitres it was significantly lower at 0.17 +/- 0.06 mg/g. With this technique it was possible to separate two types of hyperthyroidism amongst 21 patients: those with low iodine concentration in the thyroid (0.15 +/- 0.08 mg/g) and those with high iodine concentration (0.42 +/- 0.12 mg/g) after iodine administration. The iodine concentration in decompensated autonomous adenomas in twelve patients was usually low (0.12 +/- 0.12 mg/g). On the other hand iodine concentration was high in the paranodular tissues and could be demonstrated on the fluorescent scintigram. The quality of the scintigram using this technique for concentrations below 0.1 mg/g is inadequate. In this situation good imates can be obtained by radionucleid scintgrams. The situation is reversed by previous administration of iodine."} {"id": "PMID:156682", "title": "[The radiographic appearances of the post-thrombotic syndrome and phlebographic control of the effect of treatment (author's transl)].", "content": "The phlebographic appearances of the post-thrombotic syndrome can be divided into four stages which are of importance with regard to diagnosis, treatment and prognosis. This division depends on the severity of the damage to the deep venous system. In addition it is necessary to define the superficial collateral circulation and to determine whether this is sufficient or not. Both before and after surgical treatment of the deep and superficial veins, it is necessary to define the situation by phlebography. The importance of serial phlebographic examinations during treatment, particularly with anticoagulants, is demonstrated by a series of cases.", "contents": "[The radiographic appearances of the post-thrombotic syndrome and phlebographic control of the effect of treatment (author's transl)]. The phlebographic appearances of the post-thrombotic syndrome can be divided into four stages which are of importance with regard to diagnosis, treatment and prognosis. This division depends on the severity of the damage to the deep venous system. In addition it is necessary to define the superficial collateral circulation and to determine whether this is sufficient or not. Both before and after surgical treatment of the deep and superficial veins, it is necessary to define the situation by phlebography. The importance of serial phlebographic examinations during treatment, particularly with anticoagulants, is demonstrated by a series of cases."} {"id": "PMID:156683", "title": "[The significance of mastalgia in breast diagnosis (a pilot study on 706 women) (author's transl)].", "content": "Of 700 women on whom mammograms were carried out for various indications, more than half complained of mastalgia. A quarter of the women had suffered frequently from diffuse breast pain, and one third complained of mastaglia. A quarter of the women had suffered frequently from diffuse breast pain, and one third had had pain for years. One third complained of local breast pain. Changes in the mammogram amongst women with diffuse breast pain were no more common than in women without symptoms. There was no correlation between the frequency of pain and the extent of a \"mastopathy\". There were no changes which could be related to the pain. Similarly there was no difference in the frequency of biopsies or women kept under observation between those with breast pain and those without. This was also true for those with local breast pain, and also for those with clinically occult conditions. Breast size was of no significance for the occurrence of pain. Neither local nor diffuse breast pain is of any specific significance in breast diagnosis.", "contents": "[The significance of mastalgia in breast diagnosis (a pilot study on 706 women) (author's transl)]. Of 700 women on whom mammograms were carried out for various indications, more than half complained of mastalgia. A quarter of the women had suffered frequently from diffuse breast pain, and one third complained of mastaglia. A quarter of the women had suffered frequently from diffuse breast pain, and one third had had pain for years. One third complained of local breast pain. Changes in the mammogram amongst women with diffuse breast pain were no more common than in women without symptoms. There was no correlation between the frequency of pain and the extent of a \"mastopathy\". There were no changes which could be related to the pain. Similarly there was no difference in the frequency of biopsies or women kept under observation between those with breast pain and those without. This was also true for those with local breast pain, and also for those with clinically occult conditions. Breast size was of no significance for the occurrence of pain. Neither local nor diffuse breast pain is of any specific significance in breast diagnosis."} {"id": "PMID:156684", "title": "[New angiographic knowledge regarding the female breast (author's transl)].", "content": "In 67 patinets with abnormal mammograms, breast angiography was performed using a \"lo-dose vaccum packed film screen system\". The authors discuss the vascular finding within and outside the tumour.", "contents": "[New angiographic knowledge regarding the female breast (author's transl)]. In 67 patinets with abnormal mammograms, breast angiography was performed using a \"lo-dose vaccum packed film screen system\". The authors discuss the vascular finding within and outside the tumour."} {"id": "PMID:156685", "title": "[The accuracy of angiography in the evaluation of benign renal tumours (author's transl)].", "content": "The authors review the literature regarding the angiography of three benign renal tumours: adenoma, angiomyolipoma and angioma. Renal adenomas area rare. Oncocytomas can be classified with papillary adenomas; they are fairly characteristic and can be diagnosed pre-operatively. The tubular, and particularly alveolar form cannot be distinguished angiographically from a carcinoma. Angiomyolipomas (hamartomas) occur in tuberous sclerosis or may be found alone. Angiography can first of all be an aid to topographic classification. Its isolated occurrence may cause difficulties in differentiation from a carcinoma. Certain angiographic signs may enable pre-operative diagnosis: the demonstration of aneurysmal arterial changes, linear course of tumour veins and the frequency of a peri-renal haematoma. Angiolipoma is the renal tumour which is most frequently complicated by pre-renal bleeding. Capillary, plexiform or cavernous angiomas are rare. If the first two are large enough (2 cm), their homogenous hypervascularisation may permit preoperative diagnosis. The diagnosis of cavernous angiomas is more difficult.", "contents": "[The accuracy of angiography in the evaluation of benign renal tumours (author's transl)]. The authors review the literature regarding the angiography of three benign renal tumours: adenoma, angiomyolipoma and angioma. Renal adenomas area rare. Oncocytomas can be classified with papillary adenomas; they are fairly characteristic and can be diagnosed pre-operatively. The tubular, and particularly alveolar form cannot be distinguished angiographically from a carcinoma. Angiomyolipomas (hamartomas) occur in tuberous sclerosis or may be found alone. Angiography can first of all be an aid to topographic classification. Its isolated occurrence may cause difficulties in differentiation from a carcinoma. Certain angiographic signs may enable pre-operative diagnosis: the demonstration of aneurysmal arterial changes, linear course of tumour veins and the frequency of a peri-renal haematoma. Angiolipoma is the renal tumour which is most frequently complicated by pre-renal bleeding. Capillary, plexiform or cavernous angiomas are rare. If the first two are large enough (2 cm), their homogenous hypervascularisation may permit preoperative diagnosis. The diagnosis of cavernous angiomas is more difficult."} {"id": "PMID:156692", "title": "Down's syndrome in Western Australia: cytogenetics and incidence.", "content": "235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.", "contents": "Down's syndrome in Western Australia: cytogenetics and incidence. 235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences."} {"id": "PMID:156693", "title": "Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues.", "content": "Isozymic heterogeneity of human phosphofructokinase was investigated by means of ATP inhibition, immunoneutralization by antihuman muscle-type and antiliver-type phosphofructokinase antisera, solubility in (NH4)2SO4 solutions, and starch gel and polyacrylamide slab gel electrophoresis. The enzymes studied by these methods were purified from various normal and malignant human adult tissues by chromatography on blue Dextran Sepharose 4 B columns. From the results of these studied we suggest that three basic phosphofructokinase isozymes could exist: muscle-type, fibroblast-type, and liver-type isozymes. Muscle-type isozyme is the single form found in adult muscle, and is involved in the enzymes from heart, brain, red cell, and testis. Fibroblast-type isozyme is found mainly in the placenta, fibroblasts kidney, and some malignant tissues. Liver-type phosphofructokinase seems to be very definitely the predominant form in mature polymorphonuclear cells, platelets, and liver. Testis and red cell phosphofructokinase enzymes definitely include msucle-type aand liver-type subunits, associated in various hybrid forms.", "contents": "Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues. Isozymic heterogeneity of human phosphofructokinase was investigated by means of ATP inhibition, immunoneutralization by antihuman muscle-type and antiliver-type phosphofructokinase antisera, solubility in (NH4)2SO4 solutions, and starch gel and polyacrylamide slab gel electrophoresis. The enzymes studied by these methods were purified from various normal and malignant human adult tissues by chromatography on blue Dextran Sepharose 4 B columns. From the results of these studied we suggest that three basic phosphofructokinase isozymes could exist: muscle-type, fibroblast-type, and liver-type isozymes. Muscle-type isozyme is the single form found in adult muscle, and is involved in the enzymes from heart, brain, red cell, and testis. Fibroblast-type isozyme is found mainly in the placenta, fibroblasts kidney, and some malignant tissues. Liver-type phosphofructokinase seems to be very definitely the predominant form in mature polymorphonuclear cells, platelets, and liver. Testis and red cell phosphofructokinase enzymes definitely include msucle-type aand liver-type subunits, associated in various hybrid forms."} {"id": "PMID:156695", "title": "Enterochelin (enterobactin): virulence factor for Salmonella typhimurium.", "content": "The ability of Salmonella typhimurium to synthesize enterochelin (enterobactin; ENT) affects its capacity to grow both in vivo and in vitro. An ENT mutant (96-1), blocked in the conversion of chorismate to 2,3-dihydroxybenzoate, was derived from SR-11, a strain of high mouse virulence. This mutant was unchanged in the other characteristics tested: colonial, biochemical, antigenic, and cellular. In contrast to SR-11, growth of this mutant in complement-inactivated human serum was strongly inhibited. However, addition of 5 muM ENT to the cultures relieved their inhibition. Viable counts of bacteria injected into the mouse peritoneal cavity showed that without ENT, growth of 96-1 was inhibited markedly; with ENT, the apparent growth rate of 96-1 exceeded that of SR-11. The 50% lethal dose (LD50) of 96-1 was 2 to 3 log units higher than that of SR-11. When ENT was injected, the ENT- mutant exhibited an ENT-dose-related decrease in its LD50. A single injection of 300 micrograms of ENT per mouse with the inoculum reduced the LD50 of 96-1 to that of the wild-type strain. These findings support the contention that ENT is a virulence factor for S. typhimurium.", "contents": "Enterochelin (enterobactin): virulence factor for Salmonella typhimurium. The ability of Salmonella typhimurium to synthesize enterochelin (enterobactin; ENT) affects its capacity to grow both in vivo and in vitro. An ENT mutant (96-1), blocked in the conversion of chorismate to 2,3-dihydroxybenzoate, was derived from SR-11, a strain of high mouse virulence. This mutant was unchanged in the other characteristics tested: colonial, biochemical, antigenic, and cellular. In contrast to SR-11, growth of this mutant in complement-inactivated human serum was strongly inhibited. However, addition of 5 muM ENT to the cultures relieved their inhibition. Viable counts of bacteria injected into the mouse peritoneal cavity showed that without ENT, growth of 96-1 was inhibited markedly; with ENT, the apparent growth rate of 96-1 exceeded that of SR-11. The 50% lethal dose (LD50) of 96-1 was 2 to 3 log units higher than that of SR-11. When ENT was injected, the ENT- mutant exhibited an ENT-dose-related decrease in its LD50. A single injection of 300 micrograms of ENT per mouse with the inoculum reduced the LD50 of 96-1 to that of the wild-type strain. These findings support the contention that ENT is a virulence factor for S. typhimurium."} {"id": "PMID:156696", "title": "Surface mucopolysaccharides of Treponema pallidum.", "content": "The viscous mucoid fluid that accumulates within syphilitic lesions may be due to breakdown of host tissue during infection, or may be synthesized by Treponema pallidum. Experiments were performed to investigate the acidic mucopolysaccharides that occur at the surface of T. pallidum (Nichols strain). These mucopolysaccharides were demonstrated by reaction with acidified bovine serum albumin and by agglutination with wheat germ agglutinin and soybean agglutinin. The polycations ruthenium red and toluidine blue influenced treponemal survival. Concentrations of both compounds at 200 mug/ml inhibited survival, whereas concentrations at 0.1mug/ml enhanced survival. The mucopolysaccharide concentration within the mucoid fluid that accumulates during intratesticular infection was determined by reaction with acidified bovine serum albumin; it ranged from 10,000 mug/ml to less than 8 mug/ml. The addition of this mucoid fluid to treponemal suspensions resulted in differing effects on T. pallidum survival. Some preparations were inhibitory, and others were stimulatory. Commercial preparations of hyaluronic acid and chondroitin sulfate at 400, 200, 100, and 50 mug/ml were detrimental to treponemal survival. The organisms exhibited pronounced clumping in the presence of the higher concentrations of hyaluronic acid. These clumps of treponemes were comprised of mucopolysaccharides as shown by acidified bovine serum albumin and toluidine blue reactions and by hyaluronidase degradation. Results are discussed in terms of the derivation and potential role of acidic mucopolysaccharides at the surface of T. pallidum.", "contents": "Surface mucopolysaccharides of Treponema pallidum. The viscous mucoid fluid that accumulates within syphilitic lesions may be due to breakdown of host tissue during infection, or may be synthesized by Treponema pallidum. Experiments were performed to investigate the acidic mucopolysaccharides that occur at the surface of T. pallidum (Nichols strain). These mucopolysaccharides were demonstrated by reaction with acidified bovine serum albumin and by agglutination with wheat germ agglutinin and soybean agglutinin. The polycations ruthenium red and toluidine blue influenced treponemal survival. Concentrations of both compounds at 200 mug/ml inhibited survival, whereas concentrations at 0.1mug/ml enhanced survival. The mucopolysaccharide concentration within the mucoid fluid that accumulates during intratesticular infection was determined by reaction with acidified bovine serum albumin; it ranged from 10,000 mug/ml to less than 8 mug/ml. The addition of this mucoid fluid to treponemal suspensions resulted in differing effects on T. pallidum survival. Some preparations were inhibitory, and others were stimulatory. Commercial preparations of hyaluronic acid and chondroitin sulfate at 400, 200, 100, and 50 mug/ml were detrimental to treponemal survival. The organisms exhibited pronounced clumping in the presence of the higher concentrations of hyaluronic acid. These clumps of treponemes were comprised of mucopolysaccharides as shown by acidified bovine serum albumin and toluidine blue reactions and by hyaluronidase degradation. Results are discussed in terms of the derivation and potential role of acidic mucopolysaccharides at the surface of T. pallidum."} {"id": "PMID:156697", "title": "Relationship of Treponema pallidum to acidic mucopolysaccharides.", "content": "Attempts were made to relate Treponema pallidum to the acidic mucopolysaccharides that occur in vivo within host ground substance and in vitro on the surface of cultured testicular cells. Infected testicular tissue was fixed and processed for transmission electron microscopy in the presence of ruthenium red. The use of this inorganic dye demonstrated the large quantity of mucopolysaccharide within testicular tissue and the intimate association of treponemes with this material. Wheat germ agglutinin and soybean agglutinin agglutinated freshly harvested trypsinized testicular cells and trypsinized cultured cells derived from normal rabbit testes (NRT). When stained with toluidine blue, both cell preparations were metachromatic. Prior treatment of cultured NRT cells with hyaluronidase slightly decreased their sensitivity to agglutination by wheat germ agglutinin and soybean agglutinin. Lectin agglutination, metachromasia, and hyaluronidase susceptibility indicated that freshly harvested testicular cells and NRT cells have surface-associated acidic mucopolysaccharides that are probably hyaluronic acid and chondroitin sulfate. A rabbit erythrocyte \"sandwich\" technique was devised to show that hyaluronidase removed wheat germ agglutinin receptors from the cultured NRT cells. Prior incubation of NRT cells with hyaluronidase, followed by the addition of T. pallidum, resulted in a reduction in numbers of treponemes attached to the NRT cells. The attachment of T. pallidum appears to be mediated through the acidic mucopolysaccharides on the surface of NRT cells. The findings are discussed in terms of the importance of host ground substance mucopolysaccharide to the syphilitic infective process.", "contents": "Relationship of Treponema pallidum to acidic mucopolysaccharides. Attempts were made to relate Treponema pallidum to the acidic mucopolysaccharides that occur in vivo within host ground substance and in vitro on the surface of cultured testicular cells. Infected testicular tissue was fixed and processed for transmission electron microscopy in the presence of ruthenium red. The use of this inorganic dye demonstrated the large quantity of mucopolysaccharide within testicular tissue and the intimate association of treponemes with this material. Wheat germ agglutinin and soybean agglutinin agglutinated freshly harvested trypsinized testicular cells and trypsinized cultured cells derived from normal rabbit testes (NRT). When stained with toluidine blue, both cell preparations were metachromatic. Prior treatment of cultured NRT cells with hyaluronidase slightly decreased their sensitivity to agglutination by wheat germ agglutinin and soybean agglutinin. Lectin agglutination, metachromasia, and hyaluronidase susceptibility indicated that freshly harvested testicular cells and NRT cells have surface-associated acidic mucopolysaccharides that are probably hyaluronic acid and chondroitin sulfate. A rabbit erythrocyte \"sandwich\" technique was devised to show that hyaluronidase removed wheat germ agglutinin receptors from the cultured NRT cells. Prior incubation of NRT cells with hyaluronidase, followed by the addition of T. pallidum, resulted in a reduction in numbers of treponemes attached to the NRT cells. The attachment of T. pallidum appears to be mediated through the acidic mucopolysaccharides on the surface of NRT cells. The findings are discussed in terms of the importance of host ground substance mucopolysaccharide to the syphilitic infective process."} {"id": "PMID:156698", "title": "Mucopolysaccharidase of Treponema pallidum.", "content": "Treponema pallidum (Nichols strain) exhibited mucopolysaccharidase activity. Acidic mucopolysaccharides were broken down more rapidly by viable treponemes than by heat-inactivated treponemes or membrane filtrates of treponemal suspensions. Ouchterlony immunodiffusion demonstrated the occurrence of antibodies to the hyaluronidase-like enzyme within syphilitic sera. After intratesticular inoculation of 2 x 10(7) to 6 x 10(7) treponemes, these anti-mucopolysaccharidase antibodies were detected between 9 and 35 days postinoculation. In addition, acidic mucopolysaccharides were present in the serum of infected animals 9 and 16 days postinoculation. Immune serum that contained antibodies to the mucopolysaccharidase restricted treponemal breakdown of acidic mucopolysaccharides. It has been previously demonstrated that immune rabbit serum contains a factor that blocks attachment of T. pallidum (Nichols strain) to cultured mammalian cells. This factor was effectively absorbed by prior incubation with bovine hyaluronidase. It is postulated that T. pallidum attaches to acidic mucopolysaccharides on the surface of cultured cells through the mucopolysaccharidase enzyme at the surface of the organisms. These findings are discussed in terms of the histopathogenesis of T. pallidum with applications to the healing immune response.", "contents": "Mucopolysaccharidase of Treponema pallidum. Treponema pallidum (Nichols strain) exhibited mucopolysaccharidase activity. Acidic mucopolysaccharides were broken down more rapidly by viable treponemes than by heat-inactivated treponemes or membrane filtrates of treponemal suspensions. Ouchterlony immunodiffusion demonstrated the occurrence of antibodies to the hyaluronidase-like enzyme within syphilitic sera. After intratesticular inoculation of 2 x 10(7) to 6 x 10(7) treponemes, these anti-mucopolysaccharidase antibodies were detected between 9 and 35 days postinoculation. In addition, acidic mucopolysaccharides were present in the serum of infected animals 9 and 16 days postinoculation. Immune serum that contained antibodies to the mucopolysaccharidase restricted treponemal breakdown of acidic mucopolysaccharides. It has been previously demonstrated that immune rabbit serum contains a factor that blocks attachment of T. pallidum (Nichols strain) to cultured mammalian cells. This factor was effectively absorbed by prior incubation with bovine hyaluronidase. It is postulated that T. pallidum attaches to acidic mucopolysaccharides on the surface of cultured cells through the mucopolysaccharidase enzyme at the surface of the organisms. These findings are discussed in terms of the histopathogenesis of T. pallidum with applications to the healing immune response."} {"id": "PMID:156699", "title": "Effect of hydrocortisone, cyclophosphamide, azathioprine and methotrexate on cutaneous delayed and arthus hypersensitivity in the rat.", "content": "The effect of 4 immunosuppressive agents--hydrocortisone (HC), cyclophosphamide (CY), azathioprine (AZ) and methotrexate (MTX)--, on cutaneous delayed-type hypersensitivity (DTH) and Arthus reactions to the intradermal injection of ovalbumin (OA) in rats sensitized to OA in Freund's complete adjuvant (FCA) was studied. Multiple doses (daily for 4 days) were given either early, beginning on the day of sensitization, or late, beginning 9 days after sensitization. Single doses were given on the day of challenge with OA. All late multiple doses of drugs except HC depressed the DTH at 24 h in the following order of decreasing magnitude: MTX, CY, AZ. The DTH at 24 h was depressed by early multiple doses of MTX at all doses, by CY at all but the lowest dose, and by AZ at the intermediate dose; HC had no effect. When the drugs were given as single late doses, only CY at the lowest dose and MTX at the higher doses effectively depressed the DTH at 24 h. Increased Arthus reactions occurred after early and late multiple doses of HC and after a late single dose of CY at the highest dose. After late multiple doses the Arthus reaction was unaffected by either CY or MTX but was depressed by all doses of AZ. HC administered as 3 injections around the time of challenge markedly depressed the delayed and Arthus reactions. These results show that each of the 4 immunosuppressive drugs could depress DTH and Arthus reaction to OA, but the degree of depression varied with the time of drug administration relative to sensitization and challenge, and the dose of drug used. Histologic examination of skin test sites showed that an apparently negative reaction did not necessarily imply total absence of a cellular inflammatory response.", "contents": "Effect of hydrocortisone, cyclophosphamide, azathioprine and methotrexate on cutaneous delayed and arthus hypersensitivity in the rat. The effect of 4 immunosuppressive agents--hydrocortisone (HC), cyclophosphamide (CY), azathioprine (AZ) and methotrexate (MTX)--, on cutaneous delayed-type hypersensitivity (DTH) and Arthus reactions to the intradermal injection of ovalbumin (OA) in rats sensitized to OA in Freund's complete adjuvant (FCA) was studied. Multiple doses (daily for 4 days) were given either early, beginning on the day of sensitization, or late, beginning 9 days after sensitization. Single doses were given on the day of challenge with OA. All late multiple doses of drugs except HC depressed the DTH at 24 h in the following order of decreasing magnitude: MTX, CY, AZ. The DTH at 24 h was depressed by early multiple doses of MTX at all doses, by CY at all but the lowest dose, and by AZ at the intermediate dose; HC had no effect. When the drugs were given as single late doses, only CY at the lowest dose and MTX at the higher doses effectively depressed the DTH at 24 h. Increased Arthus reactions occurred after early and late multiple doses of HC and after a late single dose of CY at the highest dose. After late multiple doses the Arthus reaction was unaffected by either CY or MTX but was depressed by all doses of AZ. HC administered as 3 injections around the time of challenge markedly depressed the delayed and Arthus reactions. These results show that each of the 4 immunosuppressive drugs could depress DTH and Arthus reaction to OA, but the degree of depression varied with the time of drug administration relative to sensitization and challenge, and the dose of drug used. Histologic examination of skin test sites showed that an apparently negative reaction did not necessarily imply total absence of a cellular inflammatory response."} {"id": "PMID:156700", "title": "Experimental chronic serum sickness in rats. A model of immune complex glomerulonephritis and systemic immune complex deposition.", "content": "This article describes a method of immunization that produces chronic serum sickness in rats within a relatively short time. Fisher rats, which were immunized subcutaneously three times with bovine serum albumin (BSA) in adjuvant, responded with high titers of antibodies to BSA. 2 weeks after the third subcutaneous immunization, daily increasing amounts of BSA were injected either intraperitoneally or intravenously. When an intravenous dose of 2mg of BSA was reached, the rats were given daily intravenous injections of BSA for several weeks. This procedure, which avoided death from anaphylaxis, induced severe proliferative glomerulonephritis in all the rats and produced deposition of antigen-antibody complexes in many other organs besides the kidney. This highly reproducible model of experimental chronic serum sickness in inbred animals may have applications for the study of the mechanisms of immune complex disease.", "contents": "Experimental chronic serum sickness in rats. A model of immune complex glomerulonephritis and systemic immune complex deposition. This article describes a method of immunization that produces chronic serum sickness in rats within a relatively short time. Fisher rats, which were immunized subcutaneously three times with bovine serum albumin (BSA) in adjuvant, responded with high titers of antibodies to BSA. 2 weeks after the third subcutaneous immunization, daily increasing amounts of BSA were injected either intraperitoneally or intravenously. When an intravenous dose of 2mg of BSA was reached, the rats were given daily intravenous injections of BSA for several weeks. This procedure, which avoided death from anaphylaxis, induced severe proliferative glomerulonephritis in all the rats and produced deposition of antigen-antibody complexes in many other organs besides the kidney. This highly reproducible model of experimental chronic serum sickness in inbred animals may have applications for the study of the mechanisms of immune complex disease."} {"id": "PMID:156706", "title": "[Development of acne following pregnancy (postgestational acne)].", "content": "A woman is reported, in whom acne appeared after pregnancy. There are similar conditions in postcontraceptive acne and in acne after pregnancy. For acne after pregnancy the term \"postgestative acne\" is proposed.", "contents": "[Development of acne following pregnancy (postgestational acne)]. A woman is reported, in whom acne appeared after pregnancy. There are similar conditions in postcontraceptive acne and in acne after pregnancy. For acne after pregnancy the term \"postgestative acne\" is proposed."} {"id": "PMID:156707", "title": "Integrating occupational health and safety into the health education classroom.", "content": "Given the startling number of job-related illnesses and injuries which occur every year, occupational health and safety, a hitherto neglected topic, deserves significant attention in the school health education curriculum. Youngsters need to be exposed to this field before they become indifferent or callous toward diseases and accidents in the workplace and while the opportunity still exists to weight health and safety considerations in selecting a career. In addition, when students take up regular employment, they cannot rely on industry, government, or organized labor to protect them fully from occupational illnesses and accidents; they must possess the skills and attitudes necessary to safeguard themselves. Occupational health and safety education in the schools can focus on general awareness, skill development, and job-specific information. The field can be easily and appropriately integrated with a number of current health education topics. Examples of integration are provided for eleven typical areas of a school health education curriculum.", "contents": "Integrating occupational health and safety into the health education classroom. Given the startling number of job-related illnesses and injuries which occur every year, occupational health and safety, a hitherto neglected topic, deserves significant attention in the school health education curriculum. Youngsters need to be exposed to this field before they become indifferent or callous toward diseases and accidents in the workplace and while the opportunity still exists to weight health and safety considerations in selecting a career. In addition, when students take up regular employment, they cannot rely on industry, government, or organized labor to protect them fully from occupational illnesses and accidents; they must possess the skills and attitudes necessary to safeguard themselves. Occupational health and safety education in the schools can focus on general awareness, skill development, and job-specific information. The field can be easily and appropriately integrated with a number of current health education topics. Examples of integration are provided for eleven typical areas of a school health education curriculum."} {"id": "PMID:156708", "title": "Tyrosinemia without liver or renal damage with plantar and palmar keratosis and keratitis (hypertyrosinemia type II).", "content": "A boy of 3 2/12 years of age with Richner-Hanhart syndrome (plantar and palmar keratosis and chronic keratitis) was found to have hypertyrosinemia and to excrete the hydroxyacids derived from tyrosine. A diet poor in phenylalanine and tyrosine cured the skin and corneal lesions. Clinical and biochemical observations are reported.", "contents": "Tyrosinemia without liver or renal damage with plantar and palmar keratosis and keratitis (hypertyrosinemia type II). A boy of 3 2/12 years of age with Richner-Hanhart syndrome (plantar and palmar keratosis and chronic keratitis) was found to have hypertyrosinemia and to excrete the hydroxyacids derived from tyrosine. A diet poor in phenylalanine and tyrosine cured the skin and corneal lesions. Clinical and biochemical observations are reported."} {"id": "PMID:156709", "title": "Histochemical and ultrastructural characteristics of a new muscle fibre type in avian striated muscle.", "content": "The serratus metapatagialis (SMP) muscle of the pigeon has been studied histochemically and ultrastructurally. At the gross anatomical level the SMP is clearly divisible into a peripheral whitish band and a red portion comprised predominantly of 'pale' and 'red' fibres respectively. The pale fibres possess low succinate dehydrogenase, low mitochondrial content, absence of subsarcolemmal mitochondrial aggregates, low fat, moderate glycogen, high phosphorylase, low-to-moderate regular myofibrillar adenosine triphosphatase (M-ATPase), activation of M-ATPase following acid preincubation and jagged Z bands. On the basis of these characteristics, these physiologically slow muscle fibres have been termed 'Type I white or slow-twitch glycolytic'. The SMP red fibres, however, possess high aerobic as well as glycolytic capacity, high M-ATPase activity which is labile after acid preincubation and thick but straight Z bands; therefore, they are the 'Type II red or fast-twitch oxidative-glycolytic'.", "contents": "Histochemical and ultrastructural characteristics of a new muscle fibre type in avian striated muscle. The serratus metapatagialis (SMP) muscle of the pigeon has been studied histochemically and ultrastructurally. At the gross anatomical level the SMP is clearly divisible into a peripheral whitish band and a red portion comprised predominantly of 'pale' and 'red' fibres respectively. The pale fibres possess low succinate dehydrogenase, low mitochondrial content, absence of subsarcolemmal mitochondrial aggregates, low fat, moderate glycogen, high phosphorylase, low-to-moderate regular myofibrillar adenosine triphosphatase (M-ATPase), activation of M-ATPase following acid preincubation and jagged Z bands. On the basis of these characteristics, these physiologically slow muscle fibres have been termed 'Type I white or slow-twitch glycolytic'. The SMP red fibres, however, possess high aerobic as well as glycolytic capacity, high M-ATPase activity which is labile after acid preincubation and thick but straight Z bands; therefore, they are the 'Type II red or fast-twitch oxidative-glycolytic'."} {"id": "PMID:156711", "title": "Leg and splanchnic arteriovenous differences of plasma citrate in exercising man.", "content": "Arteriovenous concentration differences of plasma citrate, glucose, lactate, pyruvate, free fatty acids, acetoacetate, and 3-hydroxybutyrate were determined across the leg and the splanchnic vascular bed in six healthy subjects in postabsorptive state, during 30 min of exercise (60--70% work load) and 65 min of recovery. A release of citrate across the leg and an uptake across the splanchnic vascular bed were found. Citrate arterial-femoral venous difference at rest, -19 +/- 2 mumol/l was abolished after 5 min of exercise and rebuilt during continuous work to reach peak value, -30 +/- 3 mumol/l at 20 min recovery. During exercise increasing negative arterial-femoral venous citrate differences were inversely related to fractional glucose extraction across the leg. Arterial-hepatic venous citrate difference at rest, 10 +/- 2 mumol/l, increased twofold during recovery. The results agree with the concept that a citrate inhibition of phosphofructokinase may be of regulatory importance for muscular glycolysis and glucose uptake as well as for hepatic glycolysis and gluconeogenesis in man during exercise.", "contents": "Leg and splanchnic arteriovenous differences of plasma citrate in exercising man. Arteriovenous concentration differences of plasma citrate, glucose, lactate, pyruvate, free fatty acids, acetoacetate, and 3-hydroxybutyrate were determined across the leg and the splanchnic vascular bed in six healthy subjects in postabsorptive state, during 30 min of exercise (60--70% work load) and 65 min of recovery. A release of citrate across the leg and an uptake across the splanchnic vascular bed were found. Citrate arterial-femoral venous difference at rest, -19 +/- 2 mumol/l was abolished after 5 min of exercise and rebuilt during continuous work to reach peak value, -30 +/- 3 mumol/l at 20 min recovery. During exercise increasing negative arterial-femoral venous citrate differences were inversely related to fractional glucose extraction across the leg. Arterial-hepatic venous citrate difference at rest, 10 +/- 2 mumol/l, increased twofold during recovery. The results agree with the concept that a citrate inhibition of phosphofructokinase may be of regulatory importance for muscular glycolysis and glucose uptake as well as for hepatic glycolysis and gluconeogenesis in man during exercise."} {"id": "PMID:156712", "title": "Contribution of rib cage and abdomen-diaphragm to tidal volume during CO2 rebreathing.", "content": "In man, there is wide interindividual range in the tidal volume response to CO2. To determine which (rib cage or abdomen-diaphragm) compartment had a greater influence on this range, ventilatory response to CO2 was measured, using Read's method, in eight men and two women seated in a constant-pressure body plethysmograph. Rib cage and abdominal tidal volume was simultaneously measured using magnetometers. Correcting for body size, the tidal volume response of the abdominal compartment was similar in all subjects, whereas that of the rib cage was larger in subjects with high tidal volume response to CO2; a significant correlation was found (P less than 0.01). Rib cage volume displacement lagged behind abdominal in all subjects; phase lag was greatest in the subject with the lowest ventilatory response to CO2. These results suggest that, at high levels of ventilation, a larger volume displacement of the rib cage may reflect a more effective coupling of the diaphragm pressure generator to it or alternatively a reduction in its impedance relative to the abdominal compartment.", "contents": "Contribution of rib cage and abdomen-diaphragm to tidal volume during CO2 rebreathing. In man, there is wide interindividual range in the tidal volume response to CO2. To determine which (rib cage or abdomen-diaphragm) compartment had a greater influence on this range, ventilatory response to CO2 was measured, using Read's method, in eight men and two women seated in a constant-pressure body plethysmograph. Rib cage and abdominal tidal volume was simultaneously measured using magnetometers. Correcting for body size, the tidal volume response of the abdominal compartment was similar in all subjects, whereas that of the rib cage was larger in subjects with high tidal volume response to CO2; a significant correlation was found (P less than 0.01). Rib cage volume displacement lagged behind abdominal in all subjects; phase lag was greatest in the subject with the lowest ventilatory response to CO2. These results suggest that, at high levels of ventilation, a larger volume displacement of the rib cage may reflect a more effective coupling of the diaphragm pressure generator to it or alternatively a reduction in its impedance relative to the abdominal compartment."} {"id": "PMID:156715", "title": "Mobilization of sequestered metabolities into degradative reactions by nutritional stress in Neurospora.", "content": "The pools of arginine and ornithine rapidly disappear during nitrogen starvation of Neurospora crassa. Much of this disappearance can be accounted for by degradation catalyzed by preexisting catabolic enzymes. Purine degradation is also initiated by nitrogen metabolic stress. Mobilization of these compounds into degradative reactions does not appear to be a general response to nutritional stress since neither carbon starvation nor inhibition of protein synthesis elicits this response. It is suggested that nitrogen starvation may specifically alter the distribution of arginine and ornithine between vesicles and cytosol. This would be sufficient to initiate and maintain their degradation. These result suggest that compartmentation of amino acids provides a metabolic reserve to be utilized during periods of specific nutritional stress.", "contents": "Mobilization of sequestered metabolities into degradative reactions by nutritional stress in Neurospora. The pools of arginine and ornithine rapidly disappear during nitrogen starvation of Neurospora crassa. Much of this disappearance can be accounted for by degradation catalyzed by preexisting catabolic enzymes. Purine degradation is also initiated by nitrogen metabolic stress. Mobilization of these compounds into degradative reactions does not appear to be a general response to nutritional stress since neither carbon starvation nor inhibition of protein synthesis elicits this response. It is suggested that nitrogen starvation may specifically alter the distribution of arginine and ornithine between vesicles and cytosol. This would be sufficient to initiate and maintain their degradation. These result suggest that compartmentation of amino acids provides a metabolic reserve to be utilized during periods of specific nutritional stress."} {"id": "PMID:156716", "title": "Levels of major proteins of Escherichia coli during growth at different temperatures.", "content": "The adaptation of Escherichia coli B/r to temperature was studied by measuring the levels of 133 proteins (comprising 70% of the cell's protein mass) during balanced growth in rich medium at seven temperatures from 13.5 to 46 degrees C. The growth rate of this strain in either rich or minimal medium varies as a simple function of temperature with an Arrhenius constant of approximately 13,500 cal (ca. 56,500 J) per mol from 23 to 37 degrees C, the so-called normal range; above and below this range the growth rate decreases sharply. Analysis of the detailed results indicates that (i) metabolic coordination within the normal (Arrhenius) range is largely achieved by modulation of enzyme activity rather than amount; (ii) the restricted growth that occurs outside this range is accompanied by marked changes in the levels of most of these proteins; (iii) a few proteins are thermometer-like in varying simply with temperature over the whole temperature range irrespective of the influence of temperature on cell growth; and (iv) the temperature response of half of the proteins can be predicted from current information on their metabolic role or from their variation in level in different media at 37 degrees C.", "contents": "Levels of major proteins of Escherichia coli during growth at different temperatures. The adaptation of Escherichia coli B/r to temperature was studied by measuring the levels of 133 proteins (comprising 70% of the cell's protein mass) during balanced growth in rich medium at seven temperatures from 13.5 to 46 degrees C. The growth rate of this strain in either rich or minimal medium varies as a simple function of temperature with an Arrhenius constant of approximately 13,500 cal (ca. 56,500 J) per mol from 23 to 37 degrees C, the so-called normal range; above and below this range the growth rate decreases sharply. Analysis of the detailed results indicates that (i) metabolic coordination within the normal (Arrhenius) range is largely achieved by modulation of enzyme activity rather than amount; (ii) the restricted growth that occurs outside this range is accompanied by marked changes in the levels of most of these proteins; (iii) a few proteins are thermometer-like in varying simply with temperature over the whole temperature range irrespective of the influence of temperature on cell growth; and (iv) the temperature response of half of the proteins can be predicted from current information on their metabolic role or from their variation in level in different media at 37 degrees C."} {"id": "PMID:156717", "title": "Mechanisms controlling the two phosphate uptake systems in Neurospora crassa.", "content": "The development of the high-affinity and low-affinity phosphate uptake systems of Neurospora crassa has been followed during germination and early growth. The ratio between the activities of the two systems became constant by the time exponential growth began, although the value of this ratio depended on the external phosphate concentration. The regulatory mechanisms controlling the systems were investigated by following the changes that resulted when exponentially growing germlings adapted to one phosphate concentration were shifted to a different concentration. The high-affinity system was derepressed under conditions of phosphate starvation, and inhibited irreversibly by feedback inhibition under conditions of over-supply. The low-affinity system was also derepressed and subject to feedback inhibition under comparable conditions, but, in contrast, inhibition of this system was reversible. A detailed description is given of the interplay between the systems during adaptation to changes in phosphate supply. Changes that occurred in the internal phosphate pool support the hypothesis that this metabolite is responsible for controlling the activities of the systems, either by triggering derepression of new uptake system synthesis or by inhibiting the existing system by feedback.", "contents": "Mechanisms controlling the two phosphate uptake systems in Neurospora crassa. The development of the high-affinity and low-affinity phosphate uptake systems of Neurospora crassa has been followed during germination and early growth. The ratio between the activities of the two systems became constant by the time exponential growth began, although the value of this ratio depended on the external phosphate concentration. The regulatory mechanisms controlling the systems were investigated by following the changes that resulted when exponentially growing germlings adapted to one phosphate concentration were shifted to a different concentration. The high-affinity system was derepressed under conditions of phosphate starvation, and inhibited irreversibly by feedback inhibition under conditions of over-supply. The low-affinity system was also derepressed and subject to feedback inhibition under comparable conditions, but, in contrast, inhibition of this system was reversible. A detailed description is given of the interplay between the systems during adaptation to changes in phosphate supply. Changes that occurred in the internal phosphate pool support the hypothesis that this metabolite is responsible for controlling the activities of the systems, either by triggering derepression of new uptake system synthesis or by inhibiting the existing system by feedback."} {"id": "PMID:156718", "title": "Specificity of uracil uptake in Neurospora crassa.", "content": "The specificity of uracil uptake was investigated in germinating wild-type conidia of Neurospora crassa. From comparative inhibition studies, several generalizations concerning the specificity of uracil uptake can be made. (i) The tautomeric forms of uracil analogs is an important determinant of recognition by the uptake system. (ii) Substituents at the 5 position of the pyrimidine ring may impose steric constraints on binding. (iii) The presence of a negative charge results in the loss of recognition. (iv) The double bond between the 5 and 6 carbons appears to be important for recognition. (v) Purine bases do not inhibit uracil uptake. Crude extracts of the transport-deficient mutant strain uc-5 pyr-1 were shown to have uridine 5'-monophosphate pyrophosphorylase activity comparable to that of the wild-type strain, suggesting that uracil uptake in Neurospora does not occur by a group translocation mechanism involving phosphoribosylation. Specificity studies of uridine 5'-monophosphate pyrophosphorylase indicated that phosphoribosylation was not an important determinant of the specificity of uracil uptake.", "contents": "Specificity of uracil uptake in Neurospora crassa. The specificity of uracil uptake was investigated in germinating wild-type conidia of Neurospora crassa. From comparative inhibition studies, several generalizations concerning the specificity of uracil uptake can be made. (i) The tautomeric forms of uracil analogs is an important determinant of recognition by the uptake system. (ii) Substituents at the 5 position of the pyrimidine ring may impose steric constraints on binding. (iii) The presence of a negative charge results in the loss of recognition. (iv) The double bond between the 5 and 6 carbons appears to be important for recognition. (v) Purine bases do not inhibit uracil uptake. Crude extracts of the transport-deficient mutant strain uc-5 pyr-1 were shown to have uridine 5'-monophosphate pyrophosphorylase activity comparable to that of the wild-type strain, suggesting that uracil uptake in Neurospora does not occur by a group translocation mechanism involving phosphoribosylation. Specificity studies of uridine 5'-monophosphate pyrophosphorylase indicated that phosphoribosylation was not an important determinant of the specificity of uracil uptake."} {"id": "PMID:156719", "title": "Glycogen phosphorylase from Neurospora crassa: purification of a high-specific-activity, non-phosphorylated form.", "content": "A highly active glycogen phosphorylase was purified from Neurospora crassa by polyethylene glycol fractionation at pH 6.16 combined with standard techniques (chromatography and salt fractionation). The final preparation had a specific activity of 65 +/- 5 U/mg of protein (synthetic direction, pH 6.1, 30 degrees C) and was homogeneous by the criteria of gel electrophoresis, amino-terminal analysis, gel filtration, and double immunodiffusion in two dimensions. The enzyme had a native molecular weight of 180,000 +/- 10,000 (by calibrated gel filtration and gel electrophoresis) and a subunit molecular weight of 90,000 +/- 5,000 (by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Each subunit contained one molecule of pyridoxal phosphate. No phosphoserine or phosphothreonine was detected by amino acid analysis optimized for phosphoamino acid detection. The enzyme isolated from cells grown on high-specific-activity 32Pi (as sole source of phosphorus) contained one atom of 32P per subunit. All the radioactivity was removed by procedures that removed pyridoxal phosphate. Thus, the enzyme could not be classified as an a type (phosphorylated, active in the absence of a cofactor) or as a b type (non-phosphorylated, inactive in the absence of a cofactor). The level of phosphorylase was markedly increased in mycelium taken from older cultures in which the carbon source (glucose or sucrose) had been depleted. The polyethylene glycol fractionation scheme applied at pH 7.5 to mycelial extracts of younger cultures (taken before depletion of the sugar) resulted in co-purification of glycogen phosphorylase and glycogen synthetase.", "contents": "Glycogen phosphorylase from Neurospora crassa: purification of a high-specific-activity, non-phosphorylated form. A highly active glycogen phosphorylase was purified from Neurospora crassa by polyethylene glycol fractionation at pH 6.16 combined with standard techniques (chromatography and salt fractionation). The final preparation had a specific activity of 65 +/- 5 U/mg of protein (synthetic direction, pH 6.1, 30 degrees C) and was homogeneous by the criteria of gel electrophoresis, amino-terminal analysis, gel filtration, and double immunodiffusion in two dimensions. The enzyme had a native molecular weight of 180,000 +/- 10,000 (by calibrated gel filtration and gel electrophoresis) and a subunit molecular weight of 90,000 +/- 5,000 (by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Each subunit contained one molecule of pyridoxal phosphate. No phosphoserine or phosphothreonine was detected by amino acid analysis optimized for phosphoamino acid detection. The enzyme isolated from cells grown on high-specific-activity 32Pi (as sole source of phosphorus) contained one atom of 32P per subunit. All the radioactivity was removed by procedures that removed pyridoxal phosphate. Thus, the enzyme could not be classified as an a type (phosphorylated, active in the absence of a cofactor) or as a b type (non-phosphorylated, inactive in the absence of a cofactor). The level of phosphorylase was markedly increased in mycelium taken from older cultures in which the carbon source (glucose or sucrose) had been depleted. The polyethylene glycol fractionation scheme applied at pH 7.5 to mycelial extracts of younger cultures (taken before depletion of the sugar) resulted in co-purification of glycogen phosphorylase and glycogen synthetase."} {"id": "PMID:156720", "title": "Pleiotropic effects of ribosomal mutations for cycloheximide resistance in a double-resistant homocaryon of Neurospora crassa.", "content": "Pleiotropic effects of two ribosomal mutations for cycloheximide resistance were studied in a double-resistant homocaryon. The results obtained indicated that the combination of the two ribosomal mutations results in: (i) morphological abnormalities which suggest a severe distortion in the extension of cell walls and membranes; (ii) disturbance in the normal 60S-40S subunit ratio; (iii) decreased rate of cell mass production not necessarily associated with inbalance in the 60S-40S ratio; and (iv) cold sensitivity which does not interfere with mycelial mass production.", "contents": "Pleiotropic effects of ribosomal mutations for cycloheximide resistance in a double-resistant homocaryon of Neurospora crassa. Pleiotropic effects of two ribosomal mutations for cycloheximide resistance were studied in a double-resistant homocaryon. The results obtained indicated that the combination of the two ribosomal mutations results in: (i) morphological abnormalities which suggest a severe distortion in the extension of cell walls and membranes; (ii) disturbance in the normal 60S-40S subunit ratio; (iii) decreased rate of cell mass production not necessarily associated with inbalance in the 60S-40S ratio; and (iv) cold sensitivity which does not interfere with mycelial mass production."} {"id": "PMID:156722", "title": "Troponin C-like protein in chicken gizzard muscle.", "content": "1. A troponin C-like protein was prepared from frozen chicken gizzard by preparative polyacrylamide gel electrophoresis and its apparent molecular weight was estimated to be about 15,500 daltons. 2. In urea gel electrophoresis, the mobility of the troponin C-like protein increased slightly in the presence of Ca2+, like that of skeletal muscle troponin C. On the other hand, the mobility of the the troponin C-like protein in glycerol gel electrophoresis, unlike that of skeletal muscle troponin C, was significantly decreased by Ca2+. 3. In alkaline gel electrophoresis, the troponin C-like protein formed a Ca2+-dependent complex with troponin I or troponin T from skeletal muscle. 4. The troponin C-like protein could neutralize the inhibitory effect of skeletal muscle troponin I on the Mg2+-activated ATPase of actomyosin from rabbit skeletal muscle, but could not confer Ca2+-sensitivity on the actomyosin in the presence of troponin I and troponin T from skeletal muscle.", "contents": "Troponin C-like protein in chicken gizzard muscle. 1. A troponin C-like protein was prepared from frozen chicken gizzard by preparative polyacrylamide gel electrophoresis and its apparent molecular weight was estimated to be about 15,500 daltons. 2. In urea gel electrophoresis, the mobility of the troponin C-like protein increased slightly in the presence of Ca2+, like that of skeletal muscle troponin C. On the other hand, the mobility of the the troponin C-like protein in glycerol gel electrophoresis, unlike that of skeletal muscle troponin C, was significantly decreased by Ca2+. 3. In alkaline gel electrophoresis, the troponin C-like protein formed a Ca2+-dependent complex with troponin I or troponin T from skeletal muscle. 4. The troponin C-like protein could neutralize the inhibitory effect of skeletal muscle troponin I on the Mg2+-activated ATPase of actomyosin from rabbit skeletal muscle, but could not confer Ca2+-sensitivity on the actomyosin in the presence of troponin I and troponin T from skeletal muscle."} {"id": "PMID:156724", "title": "Phosphorylation of uterine smooth muscle myosin permits actin-activation.", "content": "Myosin was purified from ovine uterine smooth muscle. The 20,000 dalton myosin light chain was phosphorylated to varying degrees by an endogenous Ca2+ dependent kinase. The kinase and endogenous phosphatases were then removed via column chromatography. In the absence of actin neither the size of the initial phosphate burst nor the steady state Mg2+-dependent ATPase activity were affected by phosphorylation. However, phosphorylation was required for actin to increase the Mg2+-dependent ATPase activity and for the myosin to superprecipitate with actin. Ca2+ did not affect the Mg2+-dependent ATPase activity in the presence or absence of action or the rate or extent of superprecipitation with actin once phosphorylation was obtained. These data indicate that: 1) phosphorylation of the 20,000 dalton myosin light chain controls the uterine smooth muscle actomyosin interaction, 2) in the absence of actin, phosphorylation does not affect either the ATPase of myosin or the size of the initial burst of phosphate and, 3) Ca2+ is important in controlling the light chain kinase but not the actomyosin interaction.", "contents": "Phosphorylation of uterine smooth muscle myosin permits actin-activation. Myosin was purified from ovine uterine smooth muscle. The 20,000 dalton myosin light chain was phosphorylated to varying degrees by an endogenous Ca2+ dependent kinase. The kinase and endogenous phosphatases were then removed via column chromatography. In the absence of actin neither the size of the initial phosphate burst nor the steady state Mg2+-dependent ATPase activity were affected by phosphorylation. However, phosphorylation was required for actin to increase the Mg2+-dependent ATPase activity and for the myosin to superprecipitate with actin. Ca2+ did not affect the Mg2+-dependent ATPase activity in the presence or absence of action or the rate or extent of superprecipitation with actin once phosphorylation was obtained. These data indicate that: 1) phosphorylation of the 20,000 dalton myosin light chain controls the uterine smooth muscle actomyosin interaction, 2) in the absence of actin, phosphorylation does not affect either the ATPase of myosin or the size of the initial burst of phosphate and, 3) Ca2+ is important in controlling the light chain kinase but not the actomyosin interaction."} {"id": "PMID:156725", "title": "Intracellular protein degradation in Neurospora crassa.", "content": "In exponentially growing cultures of Neurospora crassa, the basal rate of protein degradation increases as the constant of the rate of growth decreases, so that in slow growing cells (mu = 0.13) the rate of protein degradation is about 25% of the rate of protein accumulation. During glucose starvation and shift-down transition of growth, the rate of protein degradation is greatly enhanced, and a moderate reduction (about 30%) of the ATP level is observed. Treatment of glucose-starved cells with 2-deoxyglucose reduces the ATP content by 70% and blocks protein degradation. The addition of cycloheximide, given at the onset of glucose starvation, prevents the enhancement of protein degradation; instead cycloheximide is without effect if added when proteolysis has already started. At a supraoptimal temperature (42 degrees C) the basal rate of protein degradation is not stimulated, contrary to the behavior observed in bacteria. Guanosine nucleotides, which appear to have a regulatory role for protein degradation in bacteria, are not found in N. crassa.", "contents": "Intracellular protein degradation in Neurospora crassa. In exponentially growing cultures of Neurospora crassa, the basal rate of protein degradation increases as the constant of the rate of growth decreases, so that in slow growing cells (mu = 0.13) the rate of protein degradation is about 25% of the rate of protein accumulation. During glucose starvation and shift-down transition of growth, the rate of protein degradation is greatly enhanced, and a moderate reduction (about 30%) of the ATP level is observed. Treatment of glucose-starved cells with 2-deoxyglucose reduces the ATP content by 70% and blocks protein degradation. The addition of cycloheximide, given at the onset of glucose starvation, prevents the enhancement of protein degradation; instead cycloheximide is without effect if added when proteolysis has already started. At a supraoptimal temperature (42 degrees C) the basal rate of protein degradation is not stimulated, contrary to the behavior observed in bacteria. Guanosine nucleotides, which appear to have a regulatory role for protein degradation in bacteria, are not found in N. crassa."} {"id": "PMID:156726", "title": "Cooperative binding of tropomyosin to muscle and Acanthamoeba actin.", "content": "Analyses of the binding of tropomyosin to muscle and Acanthamoeba actin by the use of Scatchard plots indicate that the binding exhibits strong positive cooperativity in the presence of Mg2+. The cooperative nature of the binding is not affected by the presence of 80 mm KCl, but appears to decrease somewhat in the presence of heavy meromyosin or subfragment-1. Heavy meromyosin, subfragment-1, and KCl each increase the binding affinity of actin for tropomyosin; depending on the experimental condition and the type of actin involved, the apparent binding constant, Kapp, is in the range of 1 to 4 x 10(6) M-1. Muscle actin cross-linked with glutaraldehyde failed to bind tropomyosin even when heavy meromyosin, subfragment-1, or KCl were added as inducers, although the cross-linked actin still markedly activated the heavy meromyosin ATPase.", "contents": "Cooperative binding of tropomyosin to muscle and Acanthamoeba actin. Analyses of the binding of tropomyosin to muscle and Acanthamoeba actin by the use of Scatchard plots indicate that the binding exhibits strong positive cooperativity in the presence of Mg2+. The cooperative nature of the binding is not affected by the presence of 80 mm KCl, but appears to decrease somewhat in the presence of heavy meromyosin or subfragment-1. Heavy meromyosin, subfragment-1, and KCl each increase the binding affinity of actin for tropomyosin; depending on the experimental condition and the type of actin involved, the apparent binding constant, Kapp, is in the range of 1 to 4 x 10(6) M-1. Muscle actin cross-linked with glutaraldehyde failed to bind tropomyosin even when heavy meromyosin, subfragment-1, or KCl were added as inducers, although the cross-linked actin still markedly activated the heavy meromyosin ATPase."} {"id": "PMID:156727", "title": "Megacystis (prune-belly syndrome): sonographic demonstration in utero.", "content": "Oligohydramnios and megacystis were demonstrated sonographically at a gestational age of 18 weeks. This was confirmed radiographically by direct intrauterine injection of contrast medium into the enlarged fetal bladder. The fetus was aborted. Autopsy confirmed prune-belly syndrome with megacystis secondary to urethral obstruction. This case demonstrates the ability of ultrasound to diagnose a significant structural fetal abnormality early enough to allow termination of the pregnancy.", "contents": "Megacystis (prune-belly syndrome): sonographic demonstration in utero. Oligohydramnios and megacystis were demonstrated sonographically at a gestational age of 18 weeks. This was confirmed radiographically by direct intrauterine injection of contrast medium into the enlarged fetal bladder. The fetus was aborted. Autopsy confirmed prune-belly syndrome with megacystis secondary to urethral obstruction. This case demonstrates the ability of ultrasound to diagnose a significant structural fetal abnormality early enough to allow termination of the pregnancy."} {"id": "PMID:156728", "title": "The dynein electrophoretic bands in axonemes naturally lacking the inner or the outer arm.", "content": "Two unconventional sperm models (all motile) have been studied. The first one has only the outer arm on the doublets (the gall midge, Diplolaboncus); the second one, has only a well-developed inner arm (the eel, Anguilla). Both are devoid of central tubules and radial spokes. The gall midge sperm yields a single electrophoretic band migrating similarly to the sea urchin dynein band A; a major high-molecular-weight band is obtained from eel sperm which co-migrates with the sea urchin dynein band B. The present picture is consistent with the localization of dynein in the axoneme--namely, of an A-like band in the outer arm, and of the B band in the inner arm. Moreover, the D band is present only in the eel, where gamma-links are present. ATPase activity was localized histochemically and found to be associated with both inner and outer arms, as well as with the gamma-links.", "contents": "The dynein electrophoretic bands in axonemes naturally lacking the inner or the outer arm. Two unconventional sperm models (all motile) have been studied. The first one has only the outer arm on the doublets (the gall midge, Diplolaboncus); the second one, has only a well-developed inner arm (the eel, Anguilla). Both are devoid of central tubules and radial spokes. The gall midge sperm yields a single electrophoretic band migrating similarly to the sea urchin dynein band A; a major high-molecular-weight band is obtained from eel sperm which co-migrates with the sea urchin dynein band B. The present picture is consistent with the localization of dynein in the axoneme--namely, of an A-like band in the outer arm, and of the B band in the inner arm. Moreover, the D band is present only in the eel, where gamma-links are present. ATPase activity was localized histochemically and found to be associated with both inner and outer arms, as well as with the gamma-links."} {"id": "PMID:156729", "title": "Chick brain actin and myosin. Isolation and characterization.", "content": "Brain actin extracted from an acetone powder of chick brains was purified by a cycle of polymerization-depolymerization followed by molecular sieve chromatography. The brain actin had a subunit molecular weight of 42,000 daltons as determined by co-electrophoresis with muscle actin. It underwent salt-dependent g to f transformation to form double helical actin filaments which could be \"decorated\" by muscle myosin subfragment 1. A critical concentration for polymerization of 1.3 microM was determined by measuring either the change in viscosity or absorbance at 232 nm. Brain actin was also capable of stimulating the ATPase activity of muscle myosin. Brain myosin was isolated from whole chick brain by a procedure involving high salt extraction, ammonium sulfate fractionation and molecular sieve chromatography. The purified myosin was composed of a 200,000-dalton heavy chain and three lower molecular weight light chains. In 0.6 M KCl the brain myosin had ATPase activity which was inhibited by Mg++, stimulated by Ca++, and maximally activated by EDTA. When dialyzed against 0.1 M KCl, the brain myosin self-assembled into short bipolar filaments. The bipolar filaments associated with each other to form long concatamers, and this association was enhanced by high concentrations of Mg++ ion. The brain myosin did not interact with chicken skeletal muscle myosin to form hybrid filaments. Furthermore, antibody recognition studies demonstrated that myosins from chicken brain, skeletal muscle, and smooth muscle were unique.", "contents": "Chick brain actin and myosin. Isolation and characterization. Brain actin extracted from an acetone powder of chick brains was purified by a cycle of polymerization-depolymerization followed by molecular sieve chromatography. The brain actin had a subunit molecular weight of 42,000 daltons as determined by co-electrophoresis with muscle actin. It underwent salt-dependent g to f transformation to form double helical actin filaments which could be \"decorated\" by muscle myosin subfragment 1. A critical concentration for polymerization of 1.3 microM was determined by measuring either the change in viscosity or absorbance at 232 nm. Brain actin was also capable of stimulating the ATPase activity of muscle myosin. Brain myosin was isolated from whole chick brain by a procedure involving high salt extraction, ammonium sulfate fractionation and molecular sieve chromatography. The purified myosin was composed of a 200,000-dalton heavy chain and three lower molecular weight light chains. In 0.6 M KCl the brain myosin had ATPase activity which was inhibited by Mg++, stimulated by Ca++, and maximally activated by EDTA. When dialyzed against 0.1 M KCl, the brain myosin self-assembled into short bipolar filaments. The bipolar filaments associated with each other to form long concatamers, and this association was enhanced by high concentrations of Mg++ ion. The brain myosin did not interact with chicken skeletal muscle myosin to form hybrid filaments. Furthermore, antibody recognition studies demonstrated that myosins from chicken brain, skeletal muscle, and smooth muscle were unique."} {"id": "PMID:156730", "title": "Localization of sarcoplasmic reticulum proteins in rat skeletal muscle by immunofluorescence.", "content": "Ca++-Mg++-dependent ATPase and calsequestrin, the major intrinsic and extrinsic proteins, respectively, of the sarcoplasmic reticulum, were localized in cryostat sections of adult rat skeletal muscle by immunofluorescent staining and phase-contrast microscopy. Relatively high concentrations of both the ATPase and calsequestrin were found in fast-twitch myofibers while a very low concentration of the ATPase and a moderate concentration of calsequestrin were found in slow-twitch myofibers. These findings are consistent with previous biochemical studies of the isolated sarcoplasmic reticulum of slow-twitch and fast-twitch mammalian muscles. The distribution of the ATPase in muscle fibers is distinctly different from that of calsequestrin. While calsequestrin is present only near the interface between the I- and A-band regions of the sarcomere, the ATPase is found throughout the I-band region as well as in the center of the A-band region. In comparing these results with in situ ultrastructural studies of the distribution of sarcoplasmic reticulum in fast-twitch muscle, it appears that the ATPase is rather uniformly distributed throughout the sarcoplasmic reticulum while calsequestrin is almost exclusively confined to those regions of the membrane system which correspond to terminal cisternae. Fluorescent staining with these antisera was not observed in vascular smooth muscle cells present in the cryostat sections of the mammalian skeletal muscle used in this study.", "contents": "Localization of sarcoplasmic reticulum proteins in rat skeletal muscle by immunofluorescence. Ca++-Mg++-dependent ATPase and calsequestrin, the major intrinsic and extrinsic proteins, respectively, of the sarcoplasmic reticulum, were localized in cryostat sections of adult rat skeletal muscle by immunofluorescent staining and phase-contrast microscopy. Relatively high concentrations of both the ATPase and calsequestrin were found in fast-twitch myofibers while a very low concentration of the ATPase and a moderate concentration of calsequestrin were found in slow-twitch myofibers. These findings are consistent with previous biochemical studies of the isolated sarcoplasmic reticulum of slow-twitch and fast-twitch mammalian muscles. The distribution of the ATPase in muscle fibers is distinctly different from that of calsequestrin. While calsequestrin is present only near the interface between the I- and A-band regions of the sarcomere, the ATPase is found throughout the I-band region as well as in the center of the A-band region. In comparing these results with in situ ultrastructural studies of the distribution of sarcoplasmic reticulum in fast-twitch muscle, it appears that the ATPase is rather uniformly distributed throughout the sarcoplasmic reticulum while calsequestrin is almost exclusively confined to those regions of the membrane system which correspond to terminal cisternae. Fluorescent staining with these antisera was not observed in vascular smooth muscle cells present in the cryostat sections of the mammalian skeletal muscle used in this study."} {"id": "PMID:156731", "title": "Effects of divalent cations on dynein cross bridging and ciliary microtubule sliding.", "content": "We recently demonstrated that addition of the divalent cation Mg++ to demembranated cilia causes the dynein arms to attach uniformly to the B subfibers. We have now studied the dose-dependent relationship between Mg++ or Ca++ and dynein bridging frequencies and microtubule sliding in cilia isolated from Tetrahymena. Both cations promote efficient dynein bridging. Mg++-induced bridges become saturated at 3 mM while Ca++-induced bridges become saturated at 2 mM. Double reciprocal plots of percent bridging vs. the cation concentration (0.05-10 mM) suggest that bridging occurs in simple equilibrium with the cation concentration. When microtubule sliding (spontaneous disintegration in 40 mM N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid (HEPES), 0.1 mM ATP at pH 7.4) is assayed (A350 nm) relative to the Mg++ or Ca++ concentration, important differential effects are observed. 100% Disintegration occurs in 0.5-2 mM Mg++ and the addition of 10 mM Mg++ does not inhibit the response. The addition of 0.05-10 mM Ca++ to cilia reactivated with 0.1 mM ATP causes a substantial reduction in disintegration at low Ca++ concentrations and complete inhibition at concentrations greater than 3 mM. When Ca++ is added to cilia reactivated with 2 mM Mg++ and 0.1 mM ATP, the percent disintegration decreases progressively with the increasing Ca++ concentration. The addition of variable concentrations of Co++ to Mg++-activated cilia causes a similar but more effective inhibition of the disintegration response. These observations, when coupled with the relatively high concentrations of Ca++ or Co++ needed to inhibit disintegration, suggest that inhibition results from simple competition for the relevant cation-binding sites and thus may not be physiologically significant. The data do not yet reveal an interpretable relationship between percent disintegration, percent dynein bridging, and percent ATPase activity of both isolated dynein and whole cilia. However, they do illustrate that considerable (sliding) disintegration (60%) can occur under conditions that reveal only 10-15% attached dynein cross bridges.", "contents": "Effects of divalent cations on dynein cross bridging and ciliary microtubule sliding. We recently demonstrated that addition of the divalent cation Mg++ to demembranated cilia causes the dynein arms to attach uniformly to the B subfibers. We have now studied the dose-dependent relationship between Mg++ or Ca++ and dynein bridging frequencies and microtubule sliding in cilia isolated from Tetrahymena. Both cations promote efficient dynein bridging. Mg++-induced bridges become saturated at 3 mM while Ca++-induced bridges become saturated at 2 mM. Double reciprocal plots of percent bridging vs. the cation concentration (0.05-10 mM) suggest that bridging occurs in simple equilibrium with the cation concentration. When microtubule sliding (spontaneous disintegration in 40 mM N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid (HEPES), 0.1 mM ATP at pH 7.4) is assayed (A350 nm) relative to the Mg++ or Ca++ concentration, important differential effects are observed. 100% Disintegration occurs in 0.5-2 mM Mg++ and the addition of 10 mM Mg++ does not inhibit the response. The addition of 0.05-10 mM Ca++ to cilia reactivated with 0.1 mM ATP causes a substantial reduction in disintegration at low Ca++ concentrations and complete inhibition at concentrations greater than 3 mM. When Ca++ is added to cilia reactivated with 2 mM Mg++ and 0.1 mM ATP, the percent disintegration decreases progressively with the increasing Ca++ concentration. The addition of variable concentrations of Co++ to Mg++-activated cilia causes a similar but more effective inhibition of the disintegration response. These observations, when coupled with the relatively high concentrations of Ca++ or Co++ needed to inhibit disintegration, suggest that inhibition results from simple competition for the relevant cation-binding sites and thus may not be physiologically significant. The data do not yet reveal an interpretable relationship between percent disintegration, percent dynein bridging, and percent ATPase activity of both isolated dynein and whole cilia. However, they do illustrate that considerable (sliding) disintegration (60%) can occur under conditions that reveal only 10-15% attached dynein cross bridges."} {"id": "PMID:156733", "title": "Deficient 3 beta-hydroxy-5-ene steroid secretion by newborn infants.", "content": "Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.", "contents": "Deficient 3 beta-hydroxy-5-ene steroid secretion by newborn infants. Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone."} {"id": "PMID:156734", "title": "Chick embryo pancreatic transplants reverse experimental diabetes of rats.", "content": "The effectiveness of xenogeneic embryonic tissue in the treatment of experimental diabetes has been investigated in rats. The splenic lobes (80) of 15- to 18-d-old chick embryos, composed almost exclusively of endocrine tissue, were implanted directly into the hepatic parenchyma of the rat recipient. The biochemical and metabolic changes in the recipients suggest that embryonic transplants of 15-d-old chick pancreases were able to significantly improve, for a prolonged period of time (18 mo), the diabetic state of nonimmunosuppressed rats. None of the recipients of 18-d-old embryos splenic lobes exhibited a long-term improvement of the diabetic state after transplantation. The complete destruction of the pancreatic B cells of the recipients was assessed by: (a) immunocytochemical investigations of the recipient's pancreas, (b) measurement of insulin in the liver and pancreas of the recipients and (c) in situ vascular perfusion of their pancreas submitted to high glucose challenge. The results suggest that pancreatic tissue of the 15-d-old embryos is immunologically immature lacking one or several lymphocyte subsets implicated in the afferent lood of \"non-self\" recognition.", "contents": "Chick embryo pancreatic transplants reverse experimental diabetes of rats. The effectiveness of xenogeneic embryonic tissue in the treatment of experimental diabetes has been investigated in rats. The splenic lobes (80) of 15- to 18-d-old chick embryos, composed almost exclusively of endocrine tissue, were implanted directly into the hepatic parenchyma of the rat recipient. The biochemical and metabolic changes in the recipients suggest that embryonic transplants of 15-d-old chick pancreases were able to significantly improve, for a prolonged period of time (18 mo), the diabetic state of nonimmunosuppressed rats. None of the recipients of 18-d-old embryos splenic lobes exhibited a long-term improvement of the diabetic state after transplantation. The complete destruction of the pancreatic B cells of the recipients was assessed by: (a) immunocytochemical investigations of the recipient's pancreas, (b) measurement of insulin in the liver and pancreas of the recipients and (c) in situ vascular perfusion of their pancreas submitted to high glucose challenge. The results suggest that pancreatic tissue of the 15-d-old embryos is immunologically immature lacking one or several lymphocyte subsets implicated in the afferent lood of \"non-self\" recognition."} {"id": "PMID:156735", "title": "Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.", "content": "The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that is not associated with a proliferative response of the vasculature supplying the enlarged ventricle.", "contents": "Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs. The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that is not associated with a proliferative response of the vasculature supplying the enlarged ventricle."} {"id": "PMID:156736", "title": "An acid transporting enzyme in human gastric mucosa.", "content": "Isolation of a microsomal fraction from human gastric mucosa followed by density gradient centrifugation yielded a vesicular membrane preparation free of mitochondrial markers, containing a K+-activated, ouabain-insensitive ATPase with an activity of 20.7 mumol P1 released/mg protein per h. Sodium dodecyl sulfate gel electrophoresis showed that the human gastric membrane vesicles contained a major polypeptide of 110,000 daltons, which accounted for approximately or equal to 30% of the total protein stained and was phosphorylated by [gamma-32P]ATP and dephosphorylated in the presence of K+. Electron microscopy revealed the presence of vesicles with an average size of 0.13 micrometer in diameter. Addition of 0.65 microM ATP to this vesicular preparation resulted in the uptake of 17 nmol H+/mg protein which was dependent on the presence of K+. The gradient was dissipated by a combination of valinomycin and protonophore after consumption of the ATP. Incubation of fixed human fundic sections or human gastric biopsy with monospecific hog gastric membrane antibody followed by fluorescein-conjugated goat anti-rabbit gamma-globulin, showed fluorescent staining in the middle portion of the gastric glands. These data indicate that human stomach contains a H+ transport ATPase with characteristics similar to those established for lower species.", "contents": "An acid transporting enzyme in human gastric mucosa. Isolation of a microsomal fraction from human gastric mucosa followed by density gradient centrifugation yielded a vesicular membrane preparation free of mitochondrial markers, containing a K+-activated, ouabain-insensitive ATPase with an activity of 20.7 mumol P1 released/mg protein per h. Sodium dodecyl sulfate gel electrophoresis showed that the human gastric membrane vesicles contained a major polypeptide of 110,000 daltons, which accounted for approximately or equal to 30% of the total protein stained and was phosphorylated by [gamma-32P]ATP and dephosphorylated in the presence of K+. Electron microscopy revealed the presence of vesicles with an average size of 0.13 micrometer in diameter. Addition of 0.65 microM ATP to this vesicular preparation resulted in the uptake of 17 nmol H+/mg protein which was dependent on the presence of K+. The gradient was dissipated by a combination of valinomycin and protonophore after consumption of the ATP. Incubation of fixed human fundic sections or human gastric biopsy with monospecific hog gastric membrane antibody followed by fluorescein-conjugated goat anti-rabbit gamma-globulin, showed fluorescent staining in the middle portion of the gastric glands. These data indicate that human stomach contains a H+ transport ATPase with characteristics similar to those established for lower species."} {"id": "PMID:156737", "title": "Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents.", "content": "In view of the potent influences of the central nervous system on glucose metabolism and on its hormonal regulators, and our recent finding of insulin and insulin receptors throughout the central nervous systsem, we have examined extreme conditions of hyperinsulinemia (obese mice) and hypoinsulinemia (streptozotocin-treated rats) with respect to changes in brain insulin and receptor content. Sprague-Dawley rats given streptozotocin (100 mg/kg body wt) developed severe diabetes and by 48 h showed no change in brain insulin. Rats given 65 mg/kg streptozotocin also had severe diabetes, but survived longer. Both at 7 d and at 30 d after streptozotocin treatment there was no significant change in brain insulin or in brain content of insulin receptors, despite the fact that peripheral hepatic receptors were elevated and pancreatic insulin was markedly depleted. The obese mice were studied at 8-10 wk when peripheral plasma insulin concentrations were 50-fold elevated and receptors on peripheral target cells were reduced to congruent with40-50% of normal; brain insulin concentrations and receptor content were indistinguishable from those of thin littermates. Thus, brain insulin, which is typically 10 times higher than plasma insulin concentrations, and brain receptor content, which is equivalent to receptor content on peripheral tissues, appears to be regulated entirely independently of hormone and receptor in the periphery. These findings are consistent with the hypothesis that insulin in the central nervous system is synthesized by the neural elements, and plays a role in the central nervous system which is unrelated to peripheral glucose metabolism.", "contents": "Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents. In view of the potent influences of the central nervous system on glucose metabolism and on its hormonal regulators, and our recent finding of insulin and insulin receptors throughout the central nervous systsem, we have examined extreme conditions of hyperinsulinemia (obese mice) and hypoinsulinemia (streptozotocin-treated rats) with respect to changes in brain insulin and receptor content. Sprague-Dawley rats given streptozotocin (100 mg/kg body wt) developed severe diabetes and by 48 h showed no change in brain insulin. Rats given 65 mg/kg streptozotocin also had severe diabetes, but survived longer. Both at 7 d and at 30 d after streptozotocin treatment there was no significant change in brain insulin or in brain content of insulin receptors, despite the fact that peripheral hepatic receptors were elevated and pancreatic insulin was markedly depleted. The obese mice were studied at 8-10 wk when peripheral plasma insulin concentrations were 50-fold elevated and receptors on peripheral target cells were reduced to congruent with40-50% of normal; brain insulin concentrations and receptor content were indistinguishable from those of thin littermates. Thus, brain insulin, which is typically 10 times higher than plasma insulin concentrations, and brain receptor content, which is equivalent to receptor content on peripheral tissues, appears to be regulated entirely independently of hormone and receptor in the periphery. These findings are consistent with the hypothesis that insulin in the central nervous system is synthesized by the neural elements, and plays a role in the central nervous system which is unrelated to peripheral glucose metabolism."} {"id": "PMID:156738", "title": "Serotonin and the control of ventilation in awake rats.", "content": "In awake, unrestrained, intact rats, reserpine, para-chlorophenylalanine, 6-fluorotryptophan, and para-chloroamphetamine depleted whole brain serotonin and produced a substantial and sustained hyperventilation as evidenced by a 5--9 torr drop in PaCO2. Administration of 5-hydroxytryptophan to rats treated with para-chlorophenylalanine partially alleviated the hyperventilation. No change in ventilation was observed after alpha-methyltyrosine. 5,7-Dihydroxytryptamine produced contradictory results. On the basis of these pharmacological studies, we propose that some serotonin-mediated nerve transmissions might function under physiological conditions to inhibit the central nervous system output which controls normal breathing.", "contents": "Serotonin and the control of ventilation in awake rats. In awake, unrestrained, intact rats, reserpine, para-chlorophenylalanine, 6-fluorotryptophan, and para-chloroamphetamine depleted whole brain serotonin and produced a substantial and sustained hyperventilation as evidenced by a 5--9 torr drop in PaCO2. Administration of 5-hydroxytryptophan to rats treated with para-chlorophenylalanine partially alleviated the hyperventilation. No change in ventilation was observed after alpha-methyltyrosine. 5,7-Dihydroxytryptamine produced contradictory results. On the basis of these pharmacological studies, we propose that some serotonin-mediated nerve transmissions might function under physiological conditions to inhibit the central nervous system output which controls normal breathing."} {"id": "PMID:156739", "title": "The MMPI as a predictor of response to conservative treatment for low back pain.", "content": "Studies that used the MMPI to predict the response of chronic low back pain patients to standard medical treatment have not produced definitive results. Patients seen in a university hospital orthopedic back pain clinic were given the MMPI before treatment, and 6 to 12 months later 76 patients completed follow-up forms that indicated their level of intensity during the previous week and their ratings of the success of treatment in relieving their pain as well as in enabling them to return to normal activities. Predictions of poor response were made in terms of either single MMPI scales or code types. Patients with poor outcome on two of the three criteria (level of pain intensity and ability to return to normal activities) had significantly higher scores on the Hs scale. The predicted high risk code types very accurately identified patients with poor response on the same two criteria; however, the code-type procedure overpredicted poor response in the good outcome group.", "contents": "The MMPI as a predictor of response to conservative treatment for low back pain. Studies that used the MMPI to predict the response of chronic low back pain patients to standard medical treatment have not produced definitive results. Patients seen in a university hospital orthopedic back pain clinic were given the MMPI before treatment, and 6 to 12 months later 76 patients completed follow-up forms that indicated their level of intensity during the previous week and their ratings of the success of treatment in relieving their pain as well as in enabling them to return to normal activities. Predictions of poor response were made in terms of either single MMPI scales or code types. Patients with poor outcome on two of the three criteria (level of pain intensity and ability to return to normal activities) had significantly higher scores on the Hs scale. The predicted high risk code types very accurately identified patients with poor response on the same two criteria; however, the code-type procedure overpredicted poor response in the good outcome group."} {"id": "PMID:156740", "title": "Clinical limitations of the Low Back Scale.", "content": "Administered the Low Back (Lb) Scale, a special derivative of the MMPI, to 20 patients with functional low back pain and 20 patients with verifiable organic evidence for their low back complaints. The Social Desirability Scale also was administered in order to assess the test-taking attitudes of the patients. The two groups of patients were equated in terms of age and sex. The results revealed no significant differences between the functional and organic patients in scores on the Lb Scale and on the Social Desirability Scale. The findings, which were consistent with other recent studies of the Lb Scale, strongly suggested that the clinical usefulness of this scale is highly questionable.", "contents": "Clinical limitations of the Low Back Scale. Administered the Low Back (Lb) Scale, a special derivative of the MMPI, to 20 patients with functional low back pain and 20 patients with verifiable organic evidence for their low back complaints. The Social Desirability Scale also was administered in order to assess the test-taking attitudes of the patients. The two groups of patients were equated in terms of age and sex. The results revealed no significant differences between the functional and organic patients in scores on the Lb Scale and on the Social Desirability Scale. The findings, which were consistent with other recent studies of the Lb Scale, strongly suggested that the clinical usefulness of this scale is highly questionable."} {"id": "PMID:156741", "title": "A quantitative study of lipofuscin accumulation with age in normals and individuals with Down's syndrome, phenylketonuria, progeria and transneuronal atrophy.", "content": "The amount of lipofuscin in neurons of two brainstem nuclei, the inferior olivary nucleus (ION) and the lateral geniculate nucleus (LGN), was measured in the brains of 1 progeric, 2 phenylketonuric, 5 Down's syndrome and 13 normal individuals. Aggregations of lipofuscin granules in cresyl violet stained sections were examined with epi-fluorescent illumination, drawn with a camera lucida, and measured with a planimeter. The proportion of lipofuscin to cell size was a linear function of age over the age range examined, 14 to 92 years. There was no difference between progeric, phenylketonuric, Down's and normal brains in the amount of lipofuscin accumulated with age, nor was there a marked within-individual correlation between amounts of lipofuscin in the two nuclei when these amounts were subtracted from the regression line values to control for age. The proportion of lipofuscin to cell size was the same in neurons of the LGN showing transneuronal atrophy in response to right eye pathology as it was in non-atrophic neurons.", "contents": "A quantitative study of lipofuscin accumulation with age in normals and individuals with Down's syndrome, phenylketonuria, progeria and transneuronal atrophy. The amount of lipofuscin in neurons of two brainstem nuclei, the inferior olivary nucleus (ION) and the lateral geniculate nucleus (LGN), was measured in the brains of 1 progeric, 2 phenylketonuric, 5 Down's syndrome and 13 normal individuals. Aggregations of lipofuscin granules in cresyl violet stained sections were examined with epi-fluorescent illumination, drawn with a camera lucida, and measured with a planimeter. The proportion of lipofuscin to cell size was a linear function of age over the age range examined, 14 to 92 years. There was no difference between progeric, phenylketonuric, Down's and normal brains in the amount of lipofuscin accumulated with age, nor was there a marked within-individual correlation between amounts of lipofuscin in the two nuclei when these amounts were subtracted from the regression line values to control for age. The proportion of lipofuscin to cell size was the same in neurons of the LGN showing transneuronal atrophy in response to right eye pathology as it was in non-atrophic neurons."} {"id": "PMID:156745", "title": "Autonomic dysfunction in tetanus: the effects of a variety of therapeutic agents, with special refernce to morphine.", "content": "Sympathetic overactivity in tetanus is a common event and may be difficult to control. This report demonstrates the efficacy of morphine in this clinical situation and also discusses the sympathetic effects of 3 muscle relaxants, pancuronium, d-tubocurarine and alcuronium.", "contents": "Autonomic dysfunction in tetanus: the effects of a variety of therapeutic agents, with special refernce to morphine. Sympathetic overactivity in tetanus is a common event and may be difficult to control. This report demonstrates the efficacy of morphine in this clinical situation and also discusses the sympathetic effects of 3 muscle relaxants, pancuronium, d-tubocurarine and alcuronium."} {"id": "PMID:156747", "title": "Complications related to the administration of general anesthesia in 600 developmentally disabled dental patients.", "content": "A total of 600 handicapped patients had dental rehabilitation under general anesthesia during an eight-year period. Handicaps included mental retardation, cerebral palsy, Down syndrome, seizure disorders, autism, cystic fibrosis, osteogenesis imperfecta, and muscular dystrophy. No significant complications developed in the majority of patients. This is attributed to thorough preoperative evaluation, appropriate anesthetic management, and vigilant postoperative observation.", "contents": "Complications related to the administration of general anesthesia in 600 developmentally disabled dental patients. A total of 600 handicapped patients had dental rehabilitation under general anesthesia during an eight-year period. Handicaps included mental retardation, cerebral palsy, Down syndrome, seizure disorders, autism, cystic fibrosis, osteogenesis imperfecta, and muscular dystrophy. No significant complications developed in the majority of patients. This is attributed to thorough preoperative evaluation, appropriate anesthetic management, and vigilant postoperative observation."} {"id": "PMID:156749", "title": "[The myectomy of the small oblique muscle with a thread operation on the rectus superior muscle on the eye with ptosis (author's transl)].", "content": "Cuppers and Thomas, in 1975, imagined that in the presence of unilateral ptosis with paresis of the rectus superior muscle only, on this side, it was advisible to place a thread on the rectus superior adelphi muscle, in order to expect an improvement, even a recovery from ptosis, by provoking an elevation impulse of the levator muscle and of the rectus superior muscle on the eye with ptosis. The first four operations were unsuccessful. On the order hand, during the fifth operation, we were led, in addition to placing the thread, to procede on the same side, to a myectomy of the small oblique muscle. The result was excellent. Two more cases of ptosis operated in the same way have been healed too. We publish here the detailed case reports, we have tried to explain them, and to specify their indications.", "contents": "[The myectomy of the small oblique muscle with a thread operation on the rectus superior muscle on the eye with ptosis (author's transl)]. Cuppers and Thomas, in 1975, imagined that in the presence of unilateral ptosis with paresis of the rectus superior muscle only, on this side, it was advisible to place a thread on the rectus superior adelphi muscle, in order to expect an improvement, even a recovery from ptosis, by provoking an elevation impulse of the levator muscle and of the rectus superior muscle on the eye with ptosis. The first four operations were unsuccessful. On the order hand, during the fifth operation, we were led, in addition to placing the thread, to procede on the same side, to a myectomy of the small oblique muscle. The result was excellent. Two more cases of ptosis operated in the same way have been healed too. We publish here the detailed case reports, we have tried to explain them, and to specify their indications."} {"id": "PMID:156750", "title": "[Retinal detachment and argon laser prophylactic treatment (author's transl)].", "content": "We have studied 6 retinal detachments which hapened after a preventive photocoagulation with argon laser in 6 patients who had already had a severe retinal detachment on the other eye (2 anatomical success on 5 operated cases). This preventive photocoagulation was done on eyes which at the term were free of any retinal dehiscence. In this group of 6 we notice 2 giant tears (greater than 70 degrees) or 33% and 3 large tears (between 20 degrees and 70 degrees) or 33%. These high amounts do not correspond to what has been noticed before: - on the non photocoagulated fellow eyes (neither giant nor large tear) - on the whole lot of operated retinal detachments during the same period of time in our unit (2% of giant and 5,7% of large tears). We think that the responsability of laser in the development of these large lesions in predisposed eyes must be thought about. Studies on a larger scale will be necessary to have a more definite idea on this subject.", "contents": "[Retinal detachment and argon laser prophylactic treatment (author's transl)]. We have studied 6 retinal detachments which hapened after a preventive photocoagulation with argon laser in 6 patients who had already had a severe retinal detachment on the other eye (2 anatomical success on 5 operated cases). This preventive photocoagulation was done on eyes which at the term were free of any retinal dehiscence. In this group of 6 we notice 2 giant tears (greater than 70 degrees) or 33% and 3 large tears (between 20 degrees and 70 degrees) or 33%. These high amounts do not correspond to what has been noticed before: - on the non photocoagulated fellow eyes (neither giant nor large tear) - on the whole lot of operated retinal detachments during the same period of time in our unit (2% of giant and 5,7% of large tears). We think that the responsability of laser in the development of these large lesions in predisposed eyes must be thought about. Studies on a larger scale will be necessary to have a more definite idea on this subject."} {"id": "PMID:156751", "title": "[Trabeculitis and Besnier-Boeck-Schaumann disease (author's transl)].", "content": "The trabeculitis is a nodular infiltration of the trabeculae. His visualization is made after gonioscopy for hypertony or systematic examination of the angle. The alone etiology known is sarcoidosis and the treatment is corticosteroid.", "contents": "[Trabeculitis and Besnier-Boeck-Schaumann disease (author's transl)]. The trabeculitis is a nodular infiltration of the trabeculae. His visualization is made after gonioscopy for hypertony or systematic examination of the angle. The alone etiology known is sarcoidosis and the treatment is corticosteroid."} {"id": "PMID:156752", "title": "[A new method of lacrymal derivation in the canalicular obstruction (author's transl)].", "content": "The authors believe that in their experience the best method of lacrymal derivation in the canalicular obstruction is the Jone's technique. However, the post operatoire complications are numerous in this method and therefore they are looking for a new procedure of lacorhinostomy: - the type of tube is a silicone tube which has the great advantage of not irritating the tissues; - the silicone tube is introduced into the lacrymal duct. After having used this technique for four years the authors are convinced that this is the best method.", "contents": "[A new method of lacrymal derivation in the canalicular obstruction (author's transl)]. The authors believe that in their experience the best method of lacrymal derivation in the canalicular obstruction is the Jone's technique. However, the post operatoire complications are numerous in this method and therefore they are looking for a new procedure of lacorhinostomy: - the type of tube is a silicone tube which has the great advantage of not irritating the tissues; - the silicone tube is introduced into the lacrymal duct. After having used this technique for four years the authors are convinced that this is the best method."} {"id": "PMID:156753", "title": "[Corneal changes in Scheie disease. (Mucopolysaccharidosis type I S) (author's transl)].", "content": "Bilateral keratoplasty performed on a 39-year-old patient with Scheie disease gave the opportunity to study the histological, histochemical and ultrastructural lesions of both corneas. The patient showed all the characteristics signs of Scheie disease with bilateral corneal opacities, thick face, synophrys, mitral and aortic valve stenosis, bilateral carpal tunnel syndrome, stiff joints, and was of normal intelligence. 24 hours urines revealed a marked excretion of mucopolysaccharides. Histology showed scarring of the superficial stroma. Histochemistry revealed an accumulation of acid mucopolysaccharides in the keratocytes throughout the stroma. Electron microscopy showed vacuoles or pleomorphic inclusions in the keratocytes compabible with abnormal lysosomes deficient in alpha-L-iduronidase.", "contents": "[Corneal changes in Scheie disease. (Mucopolysaccharidosis type I S) (author's transl)]. Bilateral keratoplasty performed on a 39-year-old patient with Scheie disease gave the opportunity to study the histological, histochemical and ultrastructural lesions of both corneas. The patient showed all the characteristics signs of Scheie disease with bilateral corneal opacities, thick face, synophrys, mitral and aortic valve stenosis, bilateral carpal tunnel syndrome, stiff joints, and was of normal intelligence. 24 hours urines revealed a marked excretion of mucopolysaccharides. Histology showed scarring of the superficial stroma. Histochemistry revealed an accumulation of acid mucopolysaccharides in the keratocytes throughout the stroma. Electron microscopy showed vacuoles or pleomorphic inclusions in the keratocytes compabible with abnormal lysosomes deficient in alpha-L-iduronidase."} {"id": "PMID:156754", "title": "[Adenine-arabinoside in the treatment of idu-resistant herpes simplex keratitis (author's transl)].", "content": "Fifteen cases of herpes simplex epithelial keratitis, which failed to heal following IDU therapy, were treated with Ara-A 3% ointment applied fives times daily. Epithelial disease resolved in fourteen cases with Ara-A and mean healing time was 6,6 days. No sign of ocular or adnexal toxicity were noted.", "contents": "[Adenine-arabinoside in the treatment of idu-resistant herpes simplex keratitis (author's transl)]. Fifteen cases of herpes simplex epithelial keratitis, which failed to heal following IDU therapy, were treated with Ara-A 3% ointment applied fives times daily. Epithelial disease resolved in fourteen cases with Ara-A and mean healing time was 6,6 days. No sign of ocular or adnexal toxicity were noted."} {"id": "PMID:156755", "title": "[Biomicroscopy of the fundus in retinal detachment surgery (author's transl)].", "content": "Biomicroscopy of the fundus during retinal detachment surgery has the same advantages as indirect ophthalmoscopy. In addition to this, it offers three main advantages over indirect ophthalmoscopy: the observation of the fundus, in an optical cross section of the tissues, the high variation of magnification available, and the observation of the fundus without switching off the light of the operating room. Since 1976--biomicroscopy of the fundus during retinal detachment surgery has been easily performed with the surgical mobile slit lamp manufactured by the firm Zeiss. The angle of the surgical slit lamp can be reduced to 5 degrees. The slit lamp can be used either with the Zeiss OPMI 1 operating microscope or with the Zeiss OPMI 6 operating microscope. The microscope, the contact lens and the surgical instrumentation specialy fitted for biomicroscopy of the fundus during retinal detachment surgery are described. The surgical technique is dealt with, pointing out the practical details which allow for overcoming the own difficulties of biomicroscopy of the fundus during surgery.", "contents": "[Biomicroscopy of the fundus in retinal detachment surgery (author's transl)]. Biomicroscopy of the fundus during retinal detachment surgery has the same advantages as indirect ophthalmoscopy. In addition to this, it offers three main advantages over indirect ophthalmoscopy: the observation of the fundus, in an optical cross section of the tissues, the high variation of magnification available, and the observation of the fundus without switching off the light of the operating room. Since 1976--biomicroscopy of the fundus during retinal detachment surgery has been easily performed with the surgical mobile slit lamp manufactured by the firm Zeiss. The angle of the surgical slit lamp can be reduced to 5 degrees. The slit lamp can be used either with the Zeiss OPMI 1 operating microscope or with the Zeiss OPMI 6 operating microscope. The microscope, the contact lens and the surgical instrumentation specialy fitted for biomicroscopy of the fundus during retinal detachment surgery are described. The surgical technique is dealt with, pointing out the practical details which allow for overcoming the own difficulties of biomicroscopy of the fundus during surgery."} {"id": "PMID:156762", "title": "Interaction between T cells and non-T cells in suppression of cytotoxic lymphocyte responses.", "content": "Generation of cytotoxic T lymphocytes (CTL) in mixed leukocyte cultures was suppressed by a factor elaborated by alloantigen-activated T cells. This suppressor factor, CTL-TsF, in contrast to a factor that suppresses proliferative responses in mixed leukocyte reactions (MLR-TsF), was effective only when added during the first 24 hr of a 6-day-culture period. Moreover, removal of CTL-TsF 24 hr after culture initiation failed to restore CTL responses. CTL activity could be rescued from suppressed cultures, however, by addition of 2-mercaptoethanol on days 3 or 4. Similarly, transfer of nonadherent cells at 3 or 4 days from cultures treated with CTL-TsF to cultures of adherent cells initiated in control factor restored CTL responses. Mixing experiments with cells pulsed with CTL-TsF for 4 hr at culture initiation identified a target of CTL-TsF as a Thy-1 negative cell that was adherent to plastic and to Sephadex G-10. Suppression was not due to interference with physiologic accessory cell function, but more likely was accomplished via a negative signal from CTL-TsF-pulsed cells. The results thus suggest that CTL-TsF acts early, but reversibly, in the CTL differentiative process via a second suppressor effector cell, possibly a macrophage.", "contents": "Interaction between T cells and non-T cells in suppression of cytotoxic lymphocyte responses. Generation of cytotoxic T lymphocytes (CTL) in mixed leukocyte cultures was suppressed by a factor elaborated by alloantigen-activated T cells. This suppressor factor, CTL-TsF, in contrast to a factor that suppresses proliferative responses in mixed leukocyte reactions (MLR-TsF), was effective only when added during the first 24 hr of a 6-day-culture period. Moreover, removal of CTL-TsF 24 hr after culture initiation failed to restore CTL responses. CTL activity could be rescued from suppressed cultures, however, by addition of 2-mercaptoethanol on days 3 or 4. Similarly, transfer of nonadherent cells at 3 or 4 days from cultures treated with CTL-TsF to cultures of adherent cells initiated in control factor restored CTL responses. Mixing experiments with cells pulsed with CTL-TsF for 4 hr at culture initiation identified a target of CTL-TsF as a Thy-1 negative cell that was adherent to plastic and to Sephadex G-10. Suppression was not due to interference with physiologic accessory cell function, but more likely was accomplished via a negative signal from CTL-TsF-pulsed cells. The results thus suggest that CTL-TsF acts early, but reversibly, in the CTL differentiative process via a second suppressor effector cell, possibly a macrophage."} {"id": "PMID:156765", "title": "Suppressor T cells regulate the cytolytic T lymphocyte response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse.", "content": "Studies were designed to analyze the immune activities of spleen cells from mice previously injected with murine sarcoma virus (MSV) and undergoing the processes of MSV tumor growth and rejection. Fractionation of MSV-primed spleen cells according to cell size by velocity sedimentation at unit gravity showed that MSV-specific cytolytic T lymphocytes (CTL) generated in vivo underwent an apparent transition in size from large to small cells as the tumor regressed. The majority of CTL precursors, however, were invariably recovered among small to medium-sized MSV-immune cells, as revealed to CTL generation in vitro in secondary mixed leukocyte-tumor cell cultures (MLTC). Evidence was obtained for the existence in MSV-immune spleens of two suppressor cell populations capable of inhibiting CTL generation in vitro: one population probably consisted of macrophages and could be removed by treatment with carbonyl iron; the second population was comprised of T cells and inhibited the differentiation of tumor-immune CTL precursors in a selective manner. These results provide a preliminary overview of the mechanisms regulating the generation, differentiation, and activity of tumor-specific CTL in a syngeneic model system.", "contents": "Suppressor T cells regulate the cytolytic T lymphocyte response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse. Studies were designed to analyze the immune activities of spleen cells from mice previously injected with murine sarcoma virus (MSV) and undergoing the processes of MSV tumor growth and rejection. Fractionation of MSV-primed spleen cells according to cell size by velocity sedimentation at unit gravity showed that MSV-specific cytolytic T lymphocytes (CTL) generated in vivo underwent an apparent transition in size from large to small cells as the tumor regressed. The majority of CTL precursors, however, were invariably recovered among small to medium-sized MSV-immune cells, as revealed to CTL generation in vitro in secondary mixed leukocyte-tumor cell cultures (MLTC). Evidence was obtained for the existence in MSV-immune spleens of two suppressor cell populations capable of inhibiting CTL generation in vitro: one population probably consisted of macrophages and could be removed by treatment with carbonyl iron; the second population was comprised of T cells and inhibited the differentiation of tumor-immune CTL precursors in a selective manner. These results provide a preliminary overview of the mechanisms regulating the generation, differentiation, and activity of tumor-specific CTL in a syngeneic model system."} {"id": "PMID:156766", "title": "Induction of allograft tolerance after total lymphoid irradiation (TLI): development of suppressor cells of the mixed leukocyte reaction (MLR).", "content": "We searched for the presence of suppressor cells of the MLR in C57BL/Ka leads to BALB/c chimeras. The chimeras were made with total lymphoid irradiation (TLI) and marrow transplantation. Spleen cells from the old chimeras inhibited the MLR of BALB/c responder cells against C57BL/Ka stimulator cells. Inhibition was specific for the stimulator cells, since no effect on the MLR was observed with C3H or BALB.C3H stimulator cells. Maximal inhibition was achieved when the responder cells in the MLR shared the H-2 haplotype of the chimeric recipient. Spleen cells obtained from chimeras young 30 to 40 days after BM transplantation inhibited the MLR nonspecifically, since similar marked inhibition was observed regardless of the H-2 haplotype of the responder or stimulator cells. The finding of antigen-specific and nonspecific suppressor cells is similar to that observed in mice rendered tolerant to bovine serum albumin after treatment with TLI.", "contents": "Induction of allograft tolerance after total lymphoid irradiation (TLI): development of suppressor cells of the mixed leukocyte reaction (MLR). We searched for the presence of suppressor cells of the MLR in C57BL/Ka leads to BALB/c chimeras. The chimeras were made with total lymphoid irradiation (TLI) and marrow transplantation. Spleen cells from the old chimeras inhibited the MLR of BALB/c responder cells against C57BL/Ka stimulator cells. Inhibition was specific for the stimulator cells, since no effect on the MLR was observed with C3H or BALB.C3H stimulator cells. Maximal inhibition was achieved when the responder cells in the MLR shared the H-2 haplotype of the chimeric recipient. Spleen cells obtained from chimeras young 30 to 40 days after BM transplantation inhibited the MLR nonspecifically, since similar marked inhibition was observed regardless of the H-2 haplotype of the responder or stimulator cells. The finding of antigen-specific and nonspecific suppressor cells is similar to that observed in mice rendered tolerant to bovine serum albumin after treatment with TLI."} {"id": "PMID:156767", "title": "Serum eosinophil chemotactic factor levels in patients with bullous pemphigoid, drug reactions and atopic eczema.", "content": "The sera of 4 patients with bullous pemphigoid, of 5 patients with drug reactions and of 13 patients with atopic eczema were examined for the occurrence of low molecular weight eosinophil chemotactic factor (ECF) by fractionation on a Sephadex G 25 column. Almost all patients had a peripheral eosinophilia, and many had raised total serum IgE levels. ECF was demonstrated in the sera of all 4 patients with bullous pemphigoid and in 4 of 5 patients with systemic drug reactions. In contrast, the sera of the 13 patients with atopic eczema did not contain any ECF activity, nor did the 13 control sera. These findings suggest that the ECF from phagocytosing polymorphonuclear leukocytes (PMN) and/or the mast cell derived ECF-A contribute to the elevated serum ECF levels in patients with bullous pemphigoid and drug reactions. A correlation between serum ECF and IgE levels and peripheral eosinophilia could not be established.", "contents": "Serum eosinophil chemotactic factor levels in patients with bullous pemphigoid, drug reactions and atopic eczema. The sera of 4 patients with bullous pemphigoid, of 5 patients with drug reactions and of 13 patients with atopic eczema were examined for the occurrence of low molecular weight eosinophil chemotactic factor (ECF) by fractionation on a Sephadex G 25 column. Almost all patients had a peripheral eosinophilia, and many had raised total serum IgE levels. ECF was demonstrated in the sera of all 4 patients with bullous pemphigoid and in 4 of 5 patients with systemic drug reactions. In contrast, the sera of the 13 patients with atopic eczema did not contain any ECF activity, nor did the 13 control sera. These findings suggest that the ECF from phagocytosing polymorphonuclear leukocytes (PMN) and/or the mast cell derived ECF-A contribute to the elevated serum ECF levels in patients with bullous pemphigoid and drug reactions. A correlation between serum ECF and IgE levels and peripheral eosinophilia could not be established."} {"id": "PMID:156785", "title": "A new operation for repair of large ventral hernias following giant omphalocele and gastroschisis.", "content": "An operation is described for repair of skin-covered large anterior abdominal wall defects, using the patient's own tissues, without synthetic materials, and its use in three patients is reported.", "contents": "A new operation for repair of large ventral hernias following giant omphalocele and gastroschisis. An operation is described for repair of skin-covered large anterior abdominal wall defects, using the patient's own tissues, without synthetic materials, and its use in three patients is reported."} {"id": "PMID:156786", "title": "The use of peritoneoscopy in the diagnosis and treatment of complications of ventriculoperitoneal shunts in children.", "content": "Abdominal complications of ventriculoperitoneal shunts used for hydrocephalus have been diagnosed and treated by peritoneoscopy in six instances. In four children, lost catheters were retrieved, and in two cases malfunction was treated. This technique was curative in each instance, thus avoiding total shunt replacement and formal laparotomy.", "contents": "The use of peritoneoscopy in the diagnosis and treatment of complications of ventriculoperitoneal shunts in children. Abdominal complications of ventriculoperitoneal shunts used for hydrocephalus have been diagnosed and treated by peritoneoscopy in six instances. In four children, lost catheters were retrieved, and in two cases malfunction was treated. This technique was curative in each instance, thus avoiding total shunt replacement and formal laparotomy."} {"id": "PMID:156790", "title": "The role of the periodontal ligament in overdenture treatment.", "content": "The results of this experiment suggest that the periodontal ligament plays a role in the efficiency of muscular activity during chewing in patients wearing overdentures. A masticatory index as an indicator of the efficiency of masticatory movement is proposed in this research.", "contents": "The role of the periodontal ligament in overdenture treatment. The results of this experiment suggest that the periodontal ligament plays a role in the efficiency of muscular activity during chewing in patients wearing overdentures. A masticatory index as an indicator of the efficiency of masticatory movement is proposed in this research."} {"id": "PMID:156791", "title": "Stereotypes concerning normal and handicapped children.", "content": "Individuals' attitudes were assessed toward various groups of children. In study 1 the respondents were 65 male and female teachers from across the state of Kansas. In study 2 the respondents were 89 men and women in attendance at the 1978 International Conference of the Association for Children with Learning Disabilities. In both studies the evaluations of the labels \"gifted children,\" \"normal children,\" and \"physically handicapped children\" were found to be significantly more positive than the evaluations of the labels \"mentally retarded children,\" \"learning disabled children,\" and \"emotionally disturbed children.\" These results seem to indicate that definite negative stereotypes are held toward the latter three groups of children. In study 1 these findings were found to occur generally regardless of the respondents' sex, age, educational level attained, and amount of previous mainstreaming experience.", "contents": "Stereotypes concerning normal and handicapped children. Individuals' attitudes were assessed toward various groups of children. In study 1 the respondents were 65 male and female teachers from across the state of Kansas. In study 2 the respondents were 89 men and women in attendance at the 1978 International Conference of the Association for Children with Learning Disabilities. In both studies the evaluations of the labels \"gifted children,\" \"normal children,\" and \"physically handicapped children\" were found to be significantly more positive than the evaluations of the labels \"mentally retarded children,\" \"learning disabled children,\" and \"emotionally disturbed children.\" These results seem to indicate that definite negative stereotypes are held toward the latter three groups of children. In study 1 these findings were found to occur generally regardless of the respondents' sex, age, educational level attained, and amount of previous mainstreaming experience."} {"id": "PMID:156793", "title": "L-Chlorozotocin.", "content": "L-Chlorozotocin (2-[[[2-chloroethyl)nitrosoamino]carbonyl]amino]-2-deoxy-L-glucose) was synthesized in seven steps from L-arabinose for comparison with chlorozotocin, which is the D enantiomorph and an antineoplastic agent with clinical potential. Purification of the intermediate 2-amino-2-deoxy-L-glucose as the Schiff's base formed with 4-methoxybenzaldehyde ensured complete separation from the manno epimer. Comparative screening against leukemia L1210 with concurrent toxicity controls revealed no significant difference between D- and L-chlorozotocin in either activity or toxicity.", "contents": "L-Chlorozotocin. L-Chlorozotocin (2-[[[2-chloroethyl)nitrosoamino]carbonyl]amino]-2-deoxy-L-glucose) was synthesized in seven steps from L-arabinose for comparison with chlorozotocin, which is the D enantiomorph and an antineoplastic agent with clinical potential. Purification of the intermediate 2-amino-2-deoxy-L-glucose as the Schiff's base formed with 4-methoxybenzaldehyde ensured complete separation from the manno epimer. Comparative screening against leukemia L1210 with concurrent toxicity controls revealed no significant difference between D- and L-chlorozotocin in either activity or toxicity."} {"id": "PMID:156795", "title": "Purification and characterization of the 45,000-Dalton fragment from tryptic digestion of (Ca2+ + Mg2+)-adenosine triphosphatase of sarcoplasmic reticulum.", "content": "Tryptic digestion of (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum of rabbit skeletal muscle has previously been shown to cleave the enzyme initially into a 55,000-dalton fragment and a 45,000-dalton fragment. In the present study the two fragments are solubilized in sodium dodecyl sulfate (SDS) and separated by preparative polyacrylamide gel electrophoresis. The 45,000-dalton fragment is found to be a relatively nonselective, divalent cation-dependent ionophore when incorporated into an oxidized cholesterol membrane (BLM). Ionophoric activity of this fragment is inhibited by low concentrations of LaCl3, HgCl2, and various reducing agents. There appears to be one or two relatively inaccessible disulfide bonds in the 45,000-dalton fragment that are essential for transport. Addition of reducing agents inhibits the ionophoric activity of the succinylated undigested enzyme and the 45,000-dalton fragment, but has no effect on the 55,000-dalton fragment. These experiments imply that the 45,000-dalton fragment and the 55,000-dalton fragment are in a series arrangement in the membrane.", "contents": "Purification and characterization of the 45,000-Dalton fragment from tryptic digestion of (Ca2+ + Mg2+)-adenosine triphosphatase of sarcoplasmic reticulum. Tryptic digestion of (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum of rabbit skeletal muscle has previously been shown to cleave the enzyme initially into a 55,000-dalton fragment and a 45,000-dalton fragment. In the present study the two fragments are solubilized in sodium dodecyl sulfate (SDS) and separated by preparative polyacrylamide gel electrophoresis. The 45,000-dalton fragment is found to be a relatively nonselective, divalent cation-dependent ionophore when incorporated into an oxidized cholesterol membrane (BLM). Ionophoric activity of this fragment is inhibited by low concentrations of LaCl3, HgCl2, and various reducing agents. There appears to be one or two relatively inaccessible disulfide bonds in the 45,000-dalton fragment that are essential for transport. Addition of reducing agents inhibits the ionophoric activity of the succinylated undigested enzyme and the 45,000-dalton fragment, but has no effect on the 55,000-dalton fragment. These experiments imply that the 45,000-dalton fragment and the 55,000-dalton fragment are in a series arrangement in the membrane."} {"id": "PMID:156796", "title": "Intra-abdominal injuries in nonpenetrating gunshot wounds of the abdominal wall: two unusual cases.", "content": "Intra-abdominal injuries of the bowel, mesentery, and mesenteric vessels were found at laparotomy in two patients with nonpenetrating gunshot wounds of the abdominal wall. The mechanism of wounding is thought to be the temporary cavity around the wound tract. The importance of complete angiographic investigation and early exploratory laparotomy is stressed.", "contents": "Intra-abdominal injuries in nonpenetrating gunshot wounds of the abdominal wall: two unusual cases. Intra-abdominal injuries of the bowel, mesentery, and mesenteric vessels were found at laparotomy in two patients with nonpenetrating gunshot wounds of the abdominal wall. The mechanism of wounding is thought to be the temporary cavity around the wound tract. The importance of complete angiographic investigation and early exploratory laparotomy is stressed."} {"id": "PMID:156792", "title": "Reiter's aortitis with pericardial fluid, heart block and neurologic manifestations.", "content": "A man who presented with Reiter's triad and keratoderma blenorrhagicum followed by cardiac manifestations is reported. He developed mild aortic insufficiency, A-V block and pericardial effusion. Painful ophthalmoplegia occurred 5 months later with exacerbation of the cardiac complications as corticosteroids were being tapered. Retreatment with high dose corticosteroids resulted in a remarkable remission of the neurologic complications and stabilization of his cardiac manifestations now maintained for 3 years.", "contents": "Reiter's aortitis with pericardial fluid, heart block and neurologic manifestations. A man who presented with Reiter's triad and keratoderma blenorrhagicum followed by cardiac manifestations is reported. He developed mild aortic insufficiency, A-V block and pericardial effusion. Painful ophthalmoplegia occurred 5 months later with exacerbation of the cardiac complications as corticosteroids were being tapered. Retreatment with high dose corticosteroids resulted in a remarkable remission of the neurologic complications and stabilization of his cardiac manifestations now maintained for 3 years."} {"id": "PMID:156797", "title": "Idiopathic retroperitoneal fibrosis: a systemic connective tissue disease?", "content": "Renal histology of a patient with idiopathic retroperitoneal fibrosis demonstrated a proliferative crescentic glomerulonephritis with intramembranous electron-dense deposits. These findings were interpreted as being consistent with an immune complex glomerulonephritis. Serologic studies revealed a positive antismooth muscle antibody titer of 1:80 and a weakly positive antinuclear antibody titer of 1:40. No distinct systemic disease was identified. While fibrosis of the retroperitoneum can occur in association with a number of distinct pathologic conditions and pharmacologic agents, the mechanism responsible for the development of the idiopathic variety of retroperitoneal fibrosis remains unclear. Our observation of an immune complex glomerulonephritis and the cumulative data on idiopathic retroperitoneal fibrosis are consistent with the concept that the fibrosis may be a local expression of an immunologically mediated systemic disease.", "contents": "Idiopathic retroperitoneal fibrosis: a systemic connective tissue disease? Renal histology of a patient with idiopathic retroperitoneal fibrosis demonstrated a proliferative crescentic glomerulonephritis with intramembranous electron-dense deposits. These findings were interpreted as being consistent with an immune complex glomerulonephritis. Serologic studies revealed a positive antismooth muscle antibody titer of 1:80 and a weakly positive antinuclear antibody titer of 1:40. No distinct systemic disease was identified. While fibrosis of the retroperitoneum can occur in association with a number of distinct pathologic conditions and pharmacologic agents, the mechanism responsible for the development of the idiopathic variety of retroperitoneal fibrosis remains unclear. Our observation of an immune complex glomerulonephritis and the cumulative data on idiopathic retroperitoneal fibrosis are consistent with the concept that the fibrosis may be a local expression of an immunologically mediated systemic disease."} {"id": "PMID:156798", "title": "Office uroflowmetry using a maximum flow rate purge meter.", "content": "The use of a purge size rotameter for the determination of maximum urinary flow rates represents an inexpensive and non-invasive method to detect obstructive or neurogenic lower urinary tract abnormalities. We have used the device to identify successfully selected patients with such abnormalities.", "contents": "Office uroflowmetry using a maximum flow rate purge meter. The use of a purge size rotameter for the determination of maximum urinary flow rates represents an inexpensive and non-invasive method to detect obstructive or neurogenic lower urinary tract abnormalities. We have used the device to identify successfully selected patients with such abnormalities."} {"id": "PMID:156805", "title": "Presence of natural killer cells in specific-pathogen-free chickens.", "content": "Spleen cells of normal specific-pathogen-free N, P, and 15 X 7 chickens were cytotoxic in vitro for target cells of Marek's disease lymphoma line MSB-1. The natural killer (NK) cell activity, best expressed in chickens over 7 weeks old, varied among several genetic lines of chickens tested. The NK cells were thermolabile, and incubation of the cells at 37 degrees C for 30--60 minutes resulted in substantial loss of cytotoxicity. The specificity of NK effector cells was directed against common antigen(s) on tumor cell lines of diverse origin but not on normal adult or embryonic cells.", "contents": "Presence of natural killer cells in specific-pathogen-free chickens. Spleen cells of normal specific-pathogen-free N, P, and 15 X 7 chickens were cytotoxic in vitro for target cells of Marek's disease lymphoma line MSB-1. The natural killer (NK) cell activity, best expressed in chickens over 7 weeks old, varied among several genetic lines of chickens tested. The NK cells were thermolabile, and incubation of the cells at 37 degrees C for 30--60 minutes resulted in substantial loss of cytotoxicity. The specificity of NK effector cells was directed against common antigen(s) on tumor cell lines of diverse origin but not on normal adult or embryonic cells."} {"id": "PMID:156806", "title": "[Effect of chorionic gonadotropin on the urinary excretion of testosterone and other androgens in healthy men and those with coronary arteriosclerosis].", "content": "The results of studying the excretion of testosterone and other androgens with the urine after a chorionic gonadotropin load in patients with ischemic heart disease and in persons who had suffered from acute myocardial infarction are discussed. In choriogonin load stimulating the gonads, there is noticeable variability in the excretion of testosterone and epitestosterone, androstenedione, and 7-keto-dehydroepiandrosterone in the urine. The data obtained are evidence of reduced functional reserves of the sex glands in some of the patients.", "contents": "[Effect of chorionic gonadotropin on the urinary excretion of testosterone and other androgens in healthy men and those with coronary arteriosclerosis]. The results of studying the excretion of testosterone and other androgens with the urine after a chorionic gonadotropin load in patients with ischemic heart disease and in persons who had suffered from acute myocardial infarction are discussed. In choriogonin load stimulating the gonads, there is noticeable variability in the excretion of testosterone and epitestosterone, androstenedione, and 7-keto-dehydroepiandrosterone in the urine. The data obtained are evidence of reduced functional reserves of the sex glands in some of the patients."} {"id": "PMID:156804", "title": "Studies on adjuvants for human prophylactics. II. Influence of the route of injection on the activity of adjuvants to tetanus toxoid in guinea pigs.", "content": "The effects of the route of the injection and adjuvants on the immune response of guinea pigs were investigated at various stages of immune response to tetanus toxoid. Delayed-type hypersensitivity (DH) was observed as the first immune response to the toxoid before initiation of antitoxin production. The DH reaction was weak when plain toxoid was administered subcutaneously. Water-in-oil in water (w/o/w) enhanced greatly the reactivity of the immunized animals; pertussis vaccine, endotoxin and aluminium showed adjuvanticities in this order. The foot pad (fp) injection of plain toxoid promoted remarkably the induction of DH. The reactivity was enhanced considerably by w/o/w and to a less extent by aluminium. However, pertussis vaccine showed an adverse effect on DH by the fp route. Active cutaneous anaphylaxis (ACA) induced by the subcutaneous route was enhanced by w/o/w, endotoxin, pertussis vaccine and, to a less extent, by aluminium. The fp route compared with the sc route enhanced ACA by plain toxoid; w/o/w and aluminium but not endotoxin and the vaccine showed adjuvanticities. The influences of adjuvants and the route of injection on Arthus reactions were inconsistent. The effect of adjuvants on antitoxin production was quite different from that on DH when antitoxin was produced abundantly. Aluminium showed consistently a potent adjuvanticity, but activities of w/o/w, endotoxin and pertussis vaccine were inconsistent 4-6 weeks after the primary stimulus by the subcutaneous route. The adjuvant effect became less significant in the secondary response. The fp route was more favorable for antitoxin production than the subcutaneous route with most adjuvants except pertussis vaccine added to tetanus toxoid. Antitoxin production by plain toxoid was very poor when administered intraperitoneally; aluminium and w/o/w but not endotoxin showed a remarkable adjuvanticity for the antitoxin production.", "contents": "Studies on adjuvants for human prophylactics. II. Influence of the route of injection on the activity of adjuvants to tetanus toxoid in guinea pigs. The effects of the route of the injection and adjuvants on the immune response of guinea pigs were investigated at various stages of immune response to tetanus toxoid. Delayed-type hypersensitivity (DH) was observed as the first immune response to the toxoid before initiation of antitoxin production. The DH reaction was weak when plain toxoid was administered subcutaneously. Water-in-oil in water (w/o/w) enhanced greatly the reactivity of the immunized animals; pertussis vaccine, endotoxin and aluminium showed adjuvanticities in this order. The foot pad (fp) injection of plain toxoid promoted remarkably the induction of DH. The reactivity was enhanced considerably by w/o/w and to a less extent by aluminium. However, pertussis vaccine showed an adverse effect on DH by the fp route. Active cutaneous anaphylaxis (ACA) induced by the subcutaneous route was enhanced by w/o/w, endotoxin, pertussis vaccine and, to a less extent, by aluminium. The fp route compared with the sc route enhanced ACA by plain toxoid; w/o/w and aluminium but not endotoxin and the vaccine showed adjuvanticities. The influences of adjuvants and the route of injection on Arthus reactions were inconsistent. The effect of adjuvants on antitoxin production was quite different from that on DH when antitoxin was produced abundantly. Aluminium showed consistently a potent adjuvanticity, but activities of w/o/w, endotoxin and pertussis vaccine were inconsistent 4-6 weeks after the primary stimulus by the subcutaneous route. The adjuvant effect became less significant in the secondary response. The fp route was more favorable for antitoxin production than the subcutaneous route with most adjuvants except pertussis vaccine added to tetanus toxoid. Antitoxin production by plain toxoid was very poor when administered intraperitoneally; aluminium and w/o/w but not endotoxin showed a remarkable adjuvanticity for the antitoxin production."} {"id": "PMID:156811", "title": "[Radiologic findings in newborns with group B streptococcal septicemia: clinical importance of heart size and lung manifestations (author's transl)].", "content": "Chest radiographs of thirteen neonates with group B streptococcal septicemia were evaluated for signs of early diagnosis. Six of the neonates had chest radiographs as seen in idiopathic respiratory distress syndrome (RDS). Seven patients had radiologic findings consistent with neonatal pneumonia. The children with RDS were in general smaller and born prematurelly, but three neonates with x-rays resembling RDS had normal birth weights and thus were mature. Cardiomegaly was observed in a high percentage with a prevalence in children with RDS. Heart size increased in two of the three children who died, but became normal in patients recovering from infection. Three patients had pleural effusions.", "contents": "[Radiologic findings in newborns with group B streptococcal septicemia: clinical importance of heart size and lung manifestations (author's transl)]. Chest radiographs of thirteen neonates with group B streptococcal septicemia were evaluated for signs of early diagnosis. Six of the neonates had chest radiographs as seen in idiopathic respiratory distress syndrome (RDS). Seven patients had radiologic findings consistent with neonatal pneumonia. The children with RDS were in general smaller and born prematurelly, but three neonates with x-rays resembling RDS had normal birth weights and thus were mature. Cardiomegaly was observed in a high percentage with a prevalence in children with RDS. Heart size increased in two of the three children who died, but became normal in patients recovering from infection. Three patients had pleural effusions."} {"id": "PMID:156812", "title": "[The regulation of protein synthesis in heart muscle. Biochemical data, stimulative and inhibitory factors and their clinical significance (author's transl)].", "content": "The regulation of protein synthesis in heart muscle has been investigated by many authors under both normal and pathological conditions. This review summarizes the evidence for the dependence of normal heart protein synthesis from normal serum levels of insulin, amino acids, fatty acids and glucose. A decreased serum concentration of these substances causes an inhibition of heart muscle protein synthesis by 30--60%. Various drugs and other chemical lead to similar impairments of heat muscle protein synthesis. The resulting imbalance between synthesis and degradation of myocardial proteins with their half-times of 5--12 days gradually leads to a decrease in their myocellular concentration with a consequent impairment of myocardial function. Finally, the biochemial sequences are described which represent the important pathogenetic mechanisms in the development of heart muscle hypertrophy and in the adriamycin-induced cardiomyopathy.", "contents": "[The regulation of protein synthesis in heart muscle. Biochemical data, stimulative and inhibitory factors and their clinical significance (author's transl)]. The regulation of protein synthesis in heart muscle has been investigated by many authors under both normal and pathological conditions. This review summarizes the evidence for the dependence of normal heart protein synthesis from normal serum levels of insulin, amino acids, fatty acids and glucose. A decreased serum concentration of these substances causes an inhibition of heart muscle protein synthesis by 30--60%. Various drugs and other chemical lead to similar impairments of heat muscle protein synthesis. The resulting imbalance between synthesis and degradation of myocardial proteins with their half-times of 5--12 days gradually leads to a decrease in their myocellular concentration with a consequent impairment of myocardial function. Finally, the biochemial sequences are described which represent the important pathogenetic mechanisms in the development of heart muscle hypertrophy and in the adriamycin-induced cardiomyopathy."} {"id": "PMID:156813", "title": "Comprehensive urinary screening for inborn errors of complex carbohydrate metabolism.", "content": "A rapid and comprehensive urinary screening programme is presented by which most of the \"heteroglycanoses\" can be identified. The diagnoses obtained on a total of 44 patients with different storage disorders shows the usefulness of the method.", "contents": "Comprehensive urinary screening for inborn errors of complex carbohydrate metabolism. A rapid and comprehensive urinary screening programme is presented by which most of the \"heteroglycanoses\" can be identified. The diagnoses obtained on a total of 44 patients with different storage disorders shows the usefulness of the method."} {"id": "PMID:156814", "title": "[Hodgkin's disease. Results in diagnosis and treatment (author's transl)].", "content": "Optimal treatment in Hodgkin's disease requires the knowledge of the stage the disease has reached. Laboratory tests, x-ray and scintigraphy, usually, are not sufficient, but biopsies of bone marrow and liver are necessary, in special cases supplemented by laparoscopy or explorative laparotomy with splenectomy. As treatment of choice, irradiation is favored for disease restricted to lymph nodes, and cytostatics for disease complicated by severe symptoms or by organ involvement. Diagnosis and therapy should be adapted to the individual patient. New therapeutic approaches must be compared with the sometimes excellent results obtained by several institutions.", "contents": "[Hodgkin's disease. Results in diagnosis and treatment (author's transl)]. Optimal treatment in Hodgkin's disease requires the knowledge of the stage the disease has reached. Laboratory tests, x-ray and scintigraphy, usually, are not sufficient, but biopsies of bone marrow and liver are necessary, in special cases supplemented by laparoscopy or explorative laparotomy with splenectomy. As treatment of choice, irradiation is favored for disease restricted to lymph nodes, and cytostatics for disease complicated by severe symptoms or by organ involvement. Diagnosis and therapy should be adapted to the individual patient. New therapeutic approaches must be compared with the sometimes excellent results obtained by several institutions."} {"id": "PMID:156819", "title": "Properties of (Mg2 + Ca2+)-ATPase of erythrocyte membranes prepared by different procedures: influence of Mg2+, Ca2+, ATP, and protein activator.", "content": "Erythrocyte membranes prepared by three different procedures showed (Mg2+ + Ca2+)-ATPase activities differing in specific activity and in affinity for Ca2+. The (Mg2+ + Ca2+)-ATPase activity of the three preparations was stimulated to different extents by a Ca2+-dependent protein activator isolated from hemolysates. The Ca2+ affinity of the two most active preparations was decreased as the ATP concentration in the assay medium was increased. Lowering the ATP concentration from 2 mM to 2-200 microM or lowering the Mg:ATP ratio to less than one shifted the (Mg2+ + Ca2+)-ATPase activity in stepwise hemolysis membranes from mixed \"high\" and \"low\" affinity to a single high Ca2+ affinity. Membranes from which soluble proteins were extracted by EDTA (0.1 mM) in low ionic strength, or membranes prepared by the EDTA (1-10 mM) procedure, did not undergo the shift in the Ca2+ affinity with changes in ATP and MgCl2 concentrations. The EDTA-wash membranes were only weakly activated by the protein activator. It is suggested that the differences in properties of the (Mg2+ + Ca2+)-ATPase prepared by these three procedures reflect differences determined in part by the degree of association of the membrane with a soluble protein activator and changes in the state of the enzyme to a less activatable form.", "contents": "Properties of (Mg2 + Ca2+)-ATPase of erythrocyte membranes prepared by different procedures: influence of Mg2+, Ca2+, ATP, and protein activator. Erythrocyte membranes prepared by three different procedures showed (Mg2+ + Ca2+)-ATPase activities differing in specific activity and in affinity for Ca2+. The (Mg2+ + Ca2+)-ATPase activity of the three preparations was stimulated to different extents by a Ca2+-dependent protein activator isolated from hemolysates. The Ca2+ affinity of the two most active preparations was decreased as the ATP concentration in the assay medium was increased. Lowering the ATP concentration from 2 mM to 2-200 microM or lowering the Mg:ATP ratio to less than one shifted the (Mg2+ + Ca2+)-ATPase activity in stepwise hemolysis membranes from mixed \"high\" and \"low\" affinity to a single high Ca2+ affinity. Membranes from which soluble proteins were extracted by EDTA (0.1 mM) in low ionic strength, or membranes prepared by the EDTA (1-10 mM) procedure, did not undergo the shift in the Ca2+ affinity with changes in ATP and MgCl2 concentrations. The EDTA-wash membranes were only weakly activated by the protein activator. It is suggested that the differences in properties of the (Mg2+ + Ca2+)-ATPase prepared by these three procedures reflect differences determined in part by the degree of association of the membrane with a soluble protein activator and changes in the state of the enzyme to a less activatable form."} {"id": "PMID:156820", "title": "Gastrointestinal carcinoids: extrahepatic metastases and symptomatology following resection.", "content": "Of 49 patients with midgut and hindgut carcinoids, second primary distinct carcinomas occurred in 12. The most aggressive carcinoids were the 24 that arose in the distal small bowel and cecum. Of the patients affected, 15 had lymph node metastases and eight had liver metastases at the time of diagnosis. That only five patients were completely relieved of symptoms following resection was partially explained by autopsy findings in 15 patients, six of whom had metastatic extra-abdominal carcinoid without liver metastases (most commonly, bone metastases).", "contents": "Gastrointestinal carcinoids: extrahepatic metastases and symptomatology following resection. Of 49 patients with midgut and hindgut carcinoids, second primary distinct carcinomas occurred in 12. The most aggressive carcinoids were the 24 that arose in the distal small bowel and cecum. Of the patients affected, 15 had lymph node metastases and eight had liver metastases at the time of diagnosis. That only five patients were completely relieved of symptoms following resection was partially explained by autopsy findings in 15 patients, six of whom had metastatic extra-abdominal carcinoid without liver metastases (most commonly, bone metastases)."} {"id": "PMID:156821", "title": "Long-term results after surgical correction of Ebstein's anomaly: report of two cases.", "content": "Two patients with Ebstein's anomaly had valve replacement with Starr-Edwards cloth-covered valves 11 and 8 years ago. They have been asymptomatic and very active despite the absence of anticoagulation. These cases provide some of the long-term results needed for proper evaluation of the different methods of operative treatment of Ebstein's anomaly.", "contents": "Long-term results after surgical correction of Ebstein's anomaly: report of two cases. Two patients with Ebstein's anomaly had valve replacement with Starr-Edwards cloth-covered valves 11 and 8 years ago. They have been asymptomatic and very active despite the absence of anticoagulation. These cases provide some of the long-term results needed for proper evaluation of the different methods of operative treatment of Ebstein's anomaly."} {"id": "PMID:156824", "title": "Ageing of Neurospora crassa. IX. Microviscosity properties of mitochondrial membranes during normal and abnormal growth and development of an inositol auxotroph.", "content": "Microviscosity of mitochondrial membranes of an inositol auxotroph of Neurospora was measured by the method of Shinitzky, employing the fluorescent probe diphenyl-hexatriene. With high concentration of inositol, growth, morphogenesis, and cellular and biochemical phenotypes of the auxotroph are normal; whereas with low concentrations, these characteristics become abnormal and cellular and clonal senescence ensue. During normal growth and development, the critical temperatures of phase transition, the energies and volumes of fusion (delta E, V), and the microviscosities (n) at low and high temperatures changed in a cyclical \"gaussian\" manner; whereas the microviscosity at 25 degrees C remained constant. The normal developmental changes of the microviscosity properties were consistent with Brody's molecular packaging hypothesis, whereby the biochemical properties of conidia are pre-determined in conidiogenic hyphae. The microviscosity properties and their developmental change were closely correlated with other biochemical and biological properties such as the critical extremities of growth temperature, activity of membrane-bound cytochrome oxidase, and the stages of cellular differentiation. The thermodynamic properties of the membrane microviscosity support the genetic hypothesis that conidia and conidiogenic hyphae are more highly differentiated than growing hyphae. During abnormal growth and development, delta E and V of the liquid-crystalline phase underwent a precocious, but otherwise normal change at an early age; whereas subsequent cellular and mitochondrial senescence was accompanied by an abnormal increase of microviscosity and abnormally small delta E and V. With the results of other experiments and by analogy to proposed structural determinants of microviscosity properties of other biological membranes, a tentative interpretation of the molecular basis of the microviscosity properties and their normal and abnormal changes is derived. The effects of phospholipase treatment indicated that electrostatic interaction of phospholipid polar groups with membrane proteins may restrict mobility, increasing microviscosity and decreasing energies of fusion. Abnormal development or ageing of the membranes, leading to abnormally large n and small delta E, is probably a consequence of excessive lipid peroxidation and related abnormal changes of their structure.", "contents": "Ageing of Neurospora crassa. IX. Microviscosity properties of mitochondrial membranes during normal and abnormal growth and development of an inositol auxotroph. Microviscosity of mitochondrial membranes of an inositol auxotroph of Neurospora was measured by the method of Shinitzky, employing the fluorescent probe diphenyl-hexatriene. With high concentration of inositol, growth, morphogenesis, and cellular and biochemical phenotypes of the auxotroph are normal; whereas with low concentrations, these characteristics become abnormal and cellular and clonal senescence ensue. During normal growth and development, the critical temperatures of phase transition, the energies and volumes of fusion (delta E, V), and the microviscosities (n) at low and high temperatures changed in a cyclical \"gaussian\" manner; whereas the microviscosity at 25 degrees C remained constant. The normal developmental changes of the microviscosity properties were consistent with Brody's molecular packaging hypothesis, whereby the biochemical properties of conidia are pre-determined in conidiogenic hyphae. The microviscosity properties and their developmental change were closely correlated with other biochemical and biological properties such as the critical extremities of growth temperature, activity of membrane-bound cytochrome oxidase, and the stages of cellular differentiation. The thermodynamic properties of the membrane microviscosity support the genetic hypothesis that conidia and conidiogenic hyphae are more highly differentiated than growing hyphae. During abnormal growth and development, delta E and V of the liquid-crystalline phase underwent a precocious, but otherwise normal change at an early age; whereas subsequent cellular and mitochondrial senescence was accompanied by an abnormal increase of microviscosity and abnormally small delta E and V. With the results of other experiments and by analogy to proposed structural determinants of microviscosity properties of other biological membranes, a tentative interpretation of the molecular basis of the microviscosity properties and their normal and abnormal changes is derived. The effects of phospholipase treatment indicated that electrostatic interaction of phospholipid polar groups with membrane proteins may restrict mobility, increasing microviscosity and decreasing energies of fusion. Abnormal development or ageing of the membranes, leading to abnormally large n and small delta E, is probably a consequence of excessive lipid peroxidation and related abnormal changes of their structure."} {"id": "PMID:156825", "title": "Ageing of Neurospora crassa. VIII. Lethality and mutagenicity of ferrous ions, ascorbic acid, and malondialdehyde.", "content": "Ferrous ions were highly lethal and mutagenic to germinated conidia of Neurospora crassa. At comparable survival, treatment with 0.2 mM ferrous ions was 14- and 50-fold more mutagenic than ultra-violet irradiation or X-rays, respectively, in the reversion of an inositol auxotroph. Ascorbic acid alone (2 mM) was not reproducibly lethal and inhibited both the lethality and mutagenicity of ferrous ions. Bovine superoxide dismutase (SOD) completely inhibited the residual lethality of ferrous ascorbate. Protection by ascorbic acid and SOD indicates that superoxide radicals, generated by oxidation of Fe(II), are directly or indirectly mutagenic and lethal. Malondialdehyde (MDA) was lethal and appeared to be mutagenic; however, its action is probably different from that of superoxide. Therefore, superoxide-mediated production of endogenous MDA by way of peroxidation of polyunsaturated fatty acids is probably not an alternate mutagenic pathway, at least in the reversion of the allele of the inl locus examined. These results and the demonstration of superoxide-mediated decrease in the synthetic fidelity of DNA polymerase in vitro (Rana and Munkres, in preparation) warrant additional exploration of the hypothesis that endogenous cellular free radicals, generated by pre- and post-senescent metabolism, may enter into lethal and mutagenic reactions.", "contents": "Ageing of Neurospora crassa. VIII. Lethality and mutagenicity of ferrous ions, ascorbic acid, and malondialdehyde. Ferrous ions were highly lethal and mutagenic to germinated conidia of Neurospora crassa. At comparable survival, treatment with 0.2 mM ferrous ions was 14- and 50-fold more mutagenic than ultra-violet irradiation or X-rays, respectively, in the reversion of an inositol auxotroph. Ascorbic acid alone (2 mM) was not reproducibly lethal and inhibited both the lethality and mutagenicity of ferrous ions. Bovine superoxide dismutase (SOD) completely inhibited the residual lethality of ferrous ascorbate. Protection by ascorbic acid and SOD indicates that superoxide radicals, generated by oxidation of Fe(II), are directly or indirectly mutagenic and lethal. Malondialdehyde (MDA) was lethal and appeared to be mutagenic; however, its action is probably different from that of superoxide. Therefore, superoxide-mediated production of endogenous MDA by way of peroxidation of polyunsaturated fatty acids is probably not an alternate mutagenic pathway, at least in the reversion of the allele of the inl locus examined. These results and the demonstration of superoxide-mediated decrease in the synthetic fidelity of DNA polymerase in vitro (Rana and Munkres, in preparation) warrant additional exploration of the hypothesis that endogenous cellular free radicals, generated by pre- and post-senescent metabolism, may enter into lethal and mutagenic reactions."} {"id": "PMID:156826", "title": "The relevance of growth control (chalones) to the aging process.", "content": "A large amount of data suggests that a wide variety of cells and tissues contain cell-specific endogenous inhibitors of mitosis which are non species-specific. Increasingly, it appears that these chalone inhibitors are actually relatively small polypeptides capable of complexing with large molecular weight anionic molecules. The purification and chamical characterization of these inhibitors has been rendered extraordinarily difficult and the results have been very slow in forthcoming because of this ability to form complexes with anionic polyelectrolytes. Our recent understanding of this behavior should markedly accelerate our understanding and knowledge of chalone biochemistry in the future. If, in fact, chalones are ubiquitously important to the control of cell proliferation, then they will be important to our understanding of the development of post-mitotic cells and to our concepts of programmed senescence; both in turn might be important to our knowledge of the aging process.", "contents": "The relevance of growth control (chalones) to the aging process. A large amount of data suggests that a wide variety of cells and tissues contain cell-specific endogenous inhibitors of mitosis which are non species-specific. Increasingly, it appears that these chalone inhibitors are actually relatively small polypeptides capable of complexing with large molecular weight anionic molecules. The purification and chamical characterization of these inhibitors has been rendered extraordinarily difficult and the results have been very slow in forthcoming because of this ability to form complexes with anionic polyelectrolytes. Our recent understanding of this behavior should markedly accelerate our understanding and knowledge of chalone biochemistry in the future. If, in fact, chalones are ubiquitously important to the control of cell proliferation, then they will be important to our understanding of the development of post-mitotic cells and to our concepts of programmed senescence; both in turn might be important to our knowledge of the aging process."} {"id": "PMID:156827", "title": "Chalones: concepts and results.", "content": "Control of cell proliferation is executed, in part, by means of negative feedback, utilizing cell-line specific messenger substances called chalones. Although knowledge of chalone chemistry is still in its infancy, the reality of the concept can no longer be reasonably questioned. In particular, it has recently been shown that chalones are even capable of causing tumour regression both in animals and in man. In addition to overviewing the chalone concept, we show here that the chalone-induced tumour regression is readily explained in simple and plausible terms.", "contents": "Chalones: concepts and results. Control of cell proliferation is executed, in part, by means of negative feedback, utilizing cell-line specific messenger substances called chalones. Although knowledge of chalone chemistry is still in its infancy, the reality of the concept can no longer be reasonably questioned. In particular, it has recently been shown that chalones are even capable of causing tumour regression both in animals and in man. In addition to overviewing the chalone concept, we show here that the chalone-induced tumour regression is readily explained in simple and plausible terms."} {"id": "PMID:156872", "title": "Role of peritoneoscopy in the postoperative evaluation and treatment of adenocarcinoma of the exocrine pancreas.", "content": "Our experience with peritoneoscopy in the postoperative staging and evaluation of ten patients with locally unresectable adenocarcinoma of the exocrine pancreas is presented. In contrast to the German experience with previously unexplored patients, the pancreas was visualized only 30% of the time and biopsy was not possible for technical reasons. Based on our experience in these ten patients, postoperative peritoneoscopy for staging or for following the effectiveness of treatment is of limited value in carcinoma of the pancreas. Preoperative evaluation of this technique deserves greater attention.", "contents": "Role of peritoneoscopy in the postoperative evaluation and treatment of adenocarcinoma of the exocrine pancreas. Our experience with peritoneoscopy in the postoperative staging and evaluation of ten patients with locally unresectable adenocarcinoma of the exocrine pancreas is presented. In contrast to the German experience with previously unexplored patients, the pancreas was visualized only 30% of the time and biopsy was not possible for technical reasons. Based on our experience in these ten patients, postoperative peritoneoscopy for staging or for following the effectiveness of treatment is of limited value in carcinoma of the pancreas. Preoperative evaluation of this technique deserves greater attention."} {"id": "PMID:156877", "title": "[Rate of DNA synthesis and the size of replication units in cell culture of Drosophila melanogaster].", "content": "The rate of DNA replication and the size of replication units was examined by means of pulse-labeling with 3H-thymidine and DNA autoradiography in the chromsomes of Drosophila melanogaster synchronized cells culture in vitro. The center-to-center distance between adjacent labeled section of DNA fibers was taken for a size of replication unit, i.e. replicon. DNA synthesis was revealed to start simultaneously in most replicons. The rate of elongation of labeled sections of DNA fibers is about 25 mu per hour (75 kb per hour). Taking into consideration bidirectinal DNA replication the rate of DNA replication per growing point is 12.5 mu per hour (38 kb per hour). The mean size of replicon is about 60 mu (130 kb) in cell culture of Drosophila melanogaster and most of these replicons vary from 20 to 80 mu. Calculation suggests that one replicon may consist of six chromomeres each being known to be formed by a segment of DNA molecular 10 mu long on average.", "contents": "[Rate of DNA synthesis and the size of replication units in cell culture of Drosophila melanogaster]. The rate of DNA replication and the size of replication units was examined by means of pulse-labeling with 3H-thymidine and DNA autoradiography in the chromsomes of Drosophila melanogaster synchronized cells culture in vitro. The center-to-center distance between adjacent labeled section of DNA fibers was taken for a size of replication unit, i.e. replicon. DNA synthesis was revealed to start simultaneously in most replicons. The rate of elongation of labeled sections of DNA fibers is about 25 mu per hour (75 kb per hour). Taking into consideration bidirectinal DNA replication the rate of DNA replication per growing point is 12.5 mu per hour (38 kb per hour). The mean size of replicon is about 60 mu (130 kb) in cell culture of Drosophila melanogaster and most of these replicons vary from 20 to 80 mu. Calculation suggests that one replicon may consist of six chromomeres each being known to be formed by a segment of DNA molecular 10 mu long on average."} {"id": "PMID:156878", "title": "[Description of the kinetics of the two substrate reactions S1+S2 goes to and comes from S3+S4 by a generalized Monod, Wyman, Changeux model].", "content": "A number of mathematical models, generalizations of the Monod, Wyman, Changeux model, have been derived describing the kinetics of two substrate reactions S1+S2 (formula: see text) S3+S4. Protomers of the olygomeric enzyme E(R, T) undergo concerted conformational transitions of the type R in equilibrium T. Cases of ordered and random substrate and product binding to the active sites of the enzyme have been considered. The models have been shown to account for the isosteric substrate activation (sigmoidal curves upsilon (S1) and upsilon(S2) and substrate inhibition of the enzyme as well as activation by one substrate and inhibition by the other. Products can exert both activating and inhibiting isosteric effects on the enzyme. Relative advantages of the two main methods of parameter estimation, experimental-kinetic and mathematical, have been discussed. The second method has been illustrated by fitting one of the models to experimental data for substrate saturation of human platelet phosphofructokinase.", "contents": "[Description of the kinetics of the two substrate reactions S1+S2 goes to and comes from S3+S4 by a generalized Monod, Wyman, Changeux model]. A number of mathematical models, generalizations of the Monod, Wyman, Changeux model, have been derived describing the kinetics of two substrate reactions S1+S2 (formula: see text) S3+S4. Protomers of the olygomeric enzyme E(R, T) undergo concerted conformational transitions of the type R in equilibrium T. Cases of ordered and random substrate and product binding to the active sites of the enzyme have been considered. The models have been shown to account for the isosteric substrate activation (sigmoidal curves upsilon (S1) and upsilon(S2) and substrate inhibition of the enzyme as well as activation by one substrate and inhibition by the other. Products can exert both activating and inhibiting isosteric effects on the enzyme. Relative advantages of the two main methods of parameter estimation, experimental-kinetic and mathematical, have been discussed. The second method has been illustrated by fitting one of the models to experimental data for substrate saturation of human platelet phosphofructokinase."} {"id": "PMID:156879", "title": "[Modern views on mechanism of ATP hydrolysis by myosin (on the 40th anniversary of myosin enzymatic activity discovery)].", "content": "Literature data and the author's materials concerning the intermediate stages of ATP hydrolysis by myosin and actomyosin are reviewed. The scheme of hydrolytic stages based on the application of fluorescent and UV spectroscopic stop-flow and 18O exchange methods is discussed. Some unsolved problems of the hydrolytic mechanism and its relation to energy transduction in the mechanochemical act are also considered.", "contents": "[Modern views on mechanism of ATP hydrolysis by myosin (on the 40th anniversary of myosin enzymatic activity discovery)]. Literature data and the author's materials concerning the intermediate stages of ATP hydrolysis by myosin and actomyosin are reviewed. The scheme of hydrolytic stages based on the application of fluorescent and UV spectroscopic stop-flow and 18O exchange methods is discussed. Some unsolved problems of the hydrolytic mechanism and its relation to energy transduction in the mechanochemical act are also considered."} {"id": "PMID:156885", "title": "The influence of the gamma system on cross-correlated activity of Ia muscle spindles and its relation to information transmission.", "content": "In the decerebrate cat during static or slowly varying (less than 0.3 Hz) muscle stretches, the activity of muscle spindle (MS) pairs was poorly correlated and such correlation was not changed after ventral root sectioning. With slightly faster sinusoidal stretches (0.3-20 Hz) activity in pairs of MS was also poorly correlated. However, sectioning of the ventral roots produced preferential firing frequencies in the same muscle spindle pairs and increased their degree of correlation. The increase in correlation between MS activity detected after suppressing the gamma bias appeared to arise from extrinsic 60 Hz power line vibration in the range of micrometers. Nevertheless, activation of the gamma system could suppress such phase locking. When frequencies above 20 Hz were used, the gamma system could not decorrelate the MS pair activity since the two units became locked to their common input signal. It is suggested that decorrelation of MS activity by gamma influence may improve the fidelity of the information transmitted by the Ia MS ensemble by filtering distortion harmonics, as well as damping tremor oscillations in the stretch reflex loop.", "contents": "The influence of the gamma system on cross-correlated activity of Ia muscle spindles and its relation to information transmission. In the decerebrate cat during static or slowly varying (less than 0.3 Hz) muscle stretches, the activity of muscle spindle (MS) pairs was poorly correlated and such correlation was not changed after ventral root sectioning. With slightly faster sinusoidal stretches (0.3-20 Hz) activity in pairs of MS was also poorly correlated. However, sectioning of the ventral roots produced preferential firing frequencies in the same muscle spindle pairs and increased their degree of correlation. The increase in correlation between MS activity detected after suppressing the gamma bias appeared to arise from extrinsic 60 Hz power line vibration in the range of micrometers. Nevertheless, activation of the gamma system could suppress such phase locking. When frequencies above 20 Hz were used, the gamma system could not decorrelate the MS pair activity since the two units became locked to their common input signal. It is suggested that decorrelation of MS activity by gamma influence may improve the fidelity of the information transmitted by the Ia MS ensemble by filtering distortion harmonics, as well as damping tremor oscillations in the stretch reflex loop."} {"id": "PMID:156888", "title": "Laparoscopy: induction of pneumoperitoneum via transfundal puncture.", "content": "One of the most troublesome features of laparoscopy is the establishment of pneumoperitoneum. This report discusses a very simple and direct way of establishing pneumoperitoneum via transfundal puncture.", "contents": "Laparoscopy: induction of pneumoperitoneum via transfundal puncture. One of the most troublesome features of laparoscopy is the establishment of pneumoperitoneum. This report discusses a very simple and direct way of establishing pneumoperitoneum via transfundal puncture."} {"id": "PMID:156903", "title": "Low back pain in patients with and without demonstrable organic disease.", "content": "Pain descriptors of patients with low back pain were analyzed to determine their usefulness in identifying patients without demonstrable organic disease. Using a standardized back pain questionnaire which scales qualities of pain along 7 independent factors, it was possible to make clear distinctions between the subjective reports of patients with and without demonstrable organic disease of the lower back. Pain described by patients with demonstrable organic disease tends to be consistent and specific; whereas pain described by patients without demonstrable organic disease tends to be more variable and diffuse. Pain reported by the latter group was also more intense. Factors which may underlie these findings were discussed.", "contents": "Low back pain in patients with and without demonstrable organic disease. Pain descriptors of patients with low back pain were analyzed to determine their usefulness in identifying patients without demonstrable organic disease. Using a standardized back pain questionnaire which scales qualities of pain along 7 independent factors, it was possible to make clear distinctions between the subjective reports of patients with and without demonstrable organic disease of the lower back. Pain described by patients with demonstrable organic disease tends to be consistent and specific; whereas pain described by patients without demonstrable organic disease tends to be more variable and diffuse. Pain reported by the latter group was also more intense. Factors which may underlie these findings were discussed."} {"id": "PMID:156904", "title": "Myosin synthesis and enzymatic properties during thyroxine intoxication in rabbits.", "content": "Hyperthyroidism has been induced to rabbits by a daily subcutaneous injection of D-L thyroxine (0.3 mg/kg). The ventricular myosin Ca2+ ATPase was increased after one week and reached + 100 % after two weeks while the K+ EDTA ATPase remained normal. During the same period, the heart weight, and the myosin incorporation of 3H-lysine after a four hour period of labelling had increased in parallel. The enhancement of both the Ca2+ ATPase and the labelling of myosin correlate, which suggests the appearance of a new molecule during the course of intoxication. This biochemical abnormality was unchanged after treatment with propranolol.", "contents": "Myosin synthesis and enzymatic properties during thyroxine intoxication in rabbits. Hyperthyroidism has been induced to rabbits by a daily subcutaneous injection of D-L thyroxine (0.3 mg/kg). The ventricular myosin Ca2+ ATPase was increased after one week and reached + 100 % after two weeks while the K+ EDTA ATPase remained normal. During the same period, the heart weight, and the myosin incorporation of 3H-lysine after a four hour period of labelling had increased in parallel. The enhancement of both the Ca2+ ATPase and the labelling of myosin correlate, which suggests the appearance of a new molecule during the course of intoxication. This biochemical abnormality was unchanged after treatment with propranolol."} {"id": "PMID:156905", "title": "The relationship of a decline in myofibrillar ATP-ase activity to the development of severe left ventricular hypertrophy in the rat.", "content": "Abdominal aortic coarctation in the rat led to a modest degree of cardiac hypertrophy associated with normal ATPase activity of myofibrills. The addition of aortic incompetence was accompanied by the development of severe hypertrophy (approx. 75 %). During the course of this latter increase in heart weight, the Ca++ ATPase of myofibrils progressively declined to a level 36% below controls. This occurred at a time when protein synthesis was stimulated as evidenced by increased incorporation of H3 lysine into myofibrils. Results are compatible with the hypothesis that the abnormal ATPase activity reflects the synthesis of an abnormal myosin molecule.", "contents": "The relationship of a decline in myofibrillar ATP-ase activity to the development of severe left ventricular hypertrophy in the rat. Abdominal aortic coarctation in the rat led to a modest degree of cardiac hypertrophy associated with normal ATPase activity of myofibrills. The addition of aortic incompetence was accompanied by the development of severe hypertrophy (approx. 75 %). During the course of this latter increase in heart weight, the Ca++ ATPase of myofibrils progressively declined to a level 36% below controls. This occurred at a time when protein synthesis was stimulated as evidenced by increased incorporation of H3 lysine into myofibrils. Results are compatible with the hypothesis that the abnormal ATPase activity reflects the synthesis of an abnormal myosin molecule."} {"id": "PMID:156908", "title": "[Sub-umbilical laparotomy by supra-pubic disinsertion of the abdominal rectus muscles (Cherney's incision). 220 cases (author's transl)].", "content": "Used in pelvic surgery in women, supra-pubic disinsertion of the rectus muscles, combining a satisfactory aesthetic result, comfort and the possibility of enlargement, was associated with a minimum of complications (4 haematomas, 4 hernias and 2 cases of breakdown) and would be suitable as a routine approach in surgery of this type.", "contents": "[Sub-umbilical laparotomy by supra-pubic disinsertion of the abdominal rectus muscles (Cherney's incision). 220 cases (author's transl)]. Used in pelvic surgery in women, supra-pubic disinsertion of the rectus muscles, combining a satisfactory aesthetic result, comfort and the possibility of enlargement, was associated with a minimum of complications (4 haematomas, 4 hernias and 2 cases of breakdown) and would be suitable as a routine approach in surgery of this type."} {"id": "PMID:156909", "title": "[Subclavian-femoral bypass: New course (author's transl)].", "content": "An unusual course for subclavian-femoral bypass was made by tunnelisation underneath the abdominal wall rather than the skin in an elderly patient with a huge incurable incisional hernia which required the wearing of an abdominal support belt. The prosthesis passed behind the sternum and the deep surface of the abdominal wall when the belt was worn.", "contents": "[Subclavian-femoral bypass: New course (author's transl)]. An unusual course for subclavian-femoral bypass was made by tunnelisation underneath the abdominal wall rather than the skin in an elderly patient with a huge incurable incisional hernia which required the wearing of an abdominal support belt. The prosthesis passed behind the sternum and the deep surface of the abdominal wall when the belt was worn."} {"id": "PMID:156910", "title": "Nucleotide sequence and conserved features of the 5.8 S rRNA coding region of Neurospora crassa.", "content": "The nucleotide sequence of Neurospora crassa 5.8 S rDNA and adjacent regions has been determined. The deduced 5.8 S rRNA sequence of Neurospora differs from the 5.8 S rRNA sequence of Saccharomyces cerevisiae at 13 of 158 residues. Nine of these differences are clustered in a segment capable of forming a short hairpin secondary structure thought to be involved in the 28 S - 5.8 S rRNA complex. These differences occur in pairs such that the potential secondary structure is preserved.", "contents": "Nucleotide sequence and conserved features of the 5.8 S rRNA coding region of Neurospora crassa. The nucleotide sequence of Neurospora crassa 5.8 S rDNA and adjacent regions has been determined. The deduced 5.8 S rRNA sequence of Neurospora differs from the 5.8 S rRNA sequence of Saccharomyces cerevisiae at 13 of 158 residues. Nine of these differences are clustered in a segment capable of forming a short hairpin secondary structure thought to be involved in the 28 S - 5.8 S rRNA complex. These differences occur in pairs such that the potential secondary structure is preserved."} {"id": "PMID:156913", "title": "Local cutaneous allergy to monocomponent insulin.", "content": "A case is described of a patient who developed local cutaneous hypersensitivity soon after commencing treatment with monocomponent insulins (MCI). This appears to be the first record of such a case.", "contents": "Local cutaneous allergy to monocomponent insulin. A case is described of a patient who developed local cutaneous hypersensitivity soon after commencing treatment with monocomponent insulins (MCI). This appears to be the first record of such a case."} {"id": "PMID:156916", "title": "[The bronchospasmolytic and protective effects of fenoterol, ipratropium bromide, theophylline ethylenediamine and disodium cromoglicicum in inhalation challenge tests; a comparative study (author's transl)].", "content": "Two series of tests were carried out with 0.5 milligrams of fenoterol, 0.25 milligrams of ipratropium bromide (both by inhalation) and with 240 milligrams of theophylline (intravenously) in persons with extrinsic bronchial asthma. In the first series (A) the broncholytic effects of the drugs were studied by administering them after inhalation provocation tests. In series B the protective effects of the drugs were studied by giving them before the tests. Untreated probands served as controls; in series B 20 milligrams of disodium cromoglicicum were given in addition. The results in series A showed that fenoterol had significantly higher bronchospasmolytic efficacy than the other drugs which were only slightly effective. In series B, however, all four drugs had an equally potent protective action. The results indicate that regular administration of these agents benefits persons with allergic bronchial asthma whereas in acute asthmatic attacks prompt and adequate bronchospasmolysis can be induced only by sympathomimetic drugs with beta-effects.", "contents": "[The bronchospasmolytic and protective effects of fenoterol, ipratropium bromide, theophylline ethylenediamine and disodium cromoglicicum in inhalation challenge tests; a comparative study (author's transl)]. Two series of tests were carried out with 0.5 milligrams of fenoterol, 0.25 milligrams of ipratropium bromide (both by inhalation) and with 240 milligrams of theophylline (intravenously) in persons with extrinsic bronchial asthma. In the first series (A) the broncholytic effects of the drugs were studied by administering them after inhalation provocation tests. In series B the protective effects of the drugs were studied by giving them before the tests. Untreated probands served as controls; in series B 20 milligrams of disodium cromoglicicum were given in addition. The results in series A showed that fenoterol had significantly higher bronchospasmolytic efficacy than the other drugs which were only slightly effective. In series B, however, all four drugs had an equally potent protective action. The results indicate that regular administration of these agents benefits persons with allergic bronchial asthma whereas in acute asthmatic attacks prompt and adequate bronchospasmolysis can be induced only by sympathomimetic drugs with beta-effects."} {"id": "PMID:156917", "title": "[Immunological examination of lymphocytes in patients with sarcoidosis and bronchial asthma (author's transl)].", "content": "Blood lymphocytes of 31 patients with bronchial asthma and of 20 patients with sarcoidosis were isolated and investigated for the following surface markers: E-receptors (E-rosettes, a T cell characteristic), Fc-receptors (EA-rosette assay), C3-receptors (EAC-rosette assay), surface immunoglobulins (immuno-fluorescence technique). In addition, the reactivity against allogeneic lymphocytes was tested in mixed lymphocyte culture (MLC). MLC properties were defined by homozygous reference cells (so-called LD-typing). HLA-typing was performed simultaneously. The results, so far, indicate in both disease groups a series of remarkable alterations of the lymphatic subpopulations. A marked diminution of circulating T lymphocytes was encountered in some cases. The immunological results are discussed in relation to pathogenetic aspects of the diseases.", "contents": "[Immunological examination of lymphocytes in patients with sarcoidosis and bronchial asthma (author's transl)]. Blood lymphocytes of 31 patients with bronchial asthma and of 20 patients with sarcoidosis were isolated and investigated for the following surface markers: E-receptors (E-rosettes, a T cell characteristic), Fc-receptors (EA-rosette assay), C3-receptors (EAC-rosette assay), surface immunoglobulins (immuno-fluorescence technique). In addition, the reactivity against allogeneic lymphocytes was tested in mixed lymphocyte culture (MLC). MLC properties were defined by homozygous reference cells (so-called LD-typing). HLA-typing was performed simultaneously. The results, so far, indicate in both disease groups a series of remarkable alterations of the lymphatic subpopulations. A marked diminution of circulating T lymphocytes was encountered in some cases. The immunological results are discussed in relation to pathogenetic aspects of the diseases."} {"id": "PMID:156918", "title": "[Silicotuberculosis in Austria and the industrial injuries act (author's transl)].", "content": "The case material comprising all persons who developed silico-tuberculosis since it was listed as an occupational disease almost 50 years ago is analysed. The relationship between various occupations and the incidence of silicosis is reviewed with special reference to the most exposed group: the wokers in the granite quarries of Upper Austria. The changes in the clinical picture of the lesion, legal aspects, diagnostic difficulties in distinguishing between silicosis with or without complicating tuberculosis are discussed.", "contents": "[Silicotuberculosis in Austria and the industrial injuries act (author's transl)]. The case material comprising all persons who developed silico-tuberculosis since it was listed as an occupational disease almost 50 years ago is analysed. The relationship between various occupations and the incidence of silicosis is reviewed with special reference to the most exposed group: the wokers in the granite quarries of Upper Austria. The changes in the clinical picture of the lesion, legal aspects, diagnostic difficulties in distinguishing between silicosis with or without complicating tuberculosis are discussed."} {"id": "PMID:156922", "title": "Inhibition of myosin ATPase by vanadate ion.", "content": "Inhibition of the myosin ATPase by vanadate ion (Vi) has been studied in 90 mM NaCl/5 mM MgCl2/20 mM Tris-HCl, pH 8.5, at 25 degrees C. Although the onset of inhibition during the assay is slow and dependent upon Vi concentration (kapp approximately 0.3 M-1 s-1), the final level of inhibition approaches 100%, provided the Vi concentration is in slight excess over the concentration of ATPase sites. Inhibition is not reversible by dialysis or the addition of reducing agents. The source of this irreversible inhibition consists of the formation of a stable, inactive complex with the composition M . ADP . Vi (where M represents a single myosin active site). The complex has been isolated, and its mechanism of formation from M, ADP, and Vi has been studied. Omission of ATP increases the rate of formation by about 35-fold (kapp approximately 11 M-1 s-1), yet this rate is still low in comparison with the rates of simple protein-ligand association reactions. This slowness is interpreted in terms of a rate-limited isomerization step that follows the association of M+, ADP, and Vi: M+ . ADP . Vi leads to M+. ADP . Vi (+ indicates the inactive product of the isomerization). The properties of M.ADP.Vi are compared with those of the ATPase intermediate M**.ADP . Pi, and the possible role of Vi as an analog of Pi is discussed.", "contents": "Inhibition of myosin ATPase by vanadate ion. Inhibition of the myosin ATPase by vanadate ion (Vi) has been studied in 90 mM NaCl/5 mM MgCl2/20 mM Tris-HCl, pH 8.5, at 25 degrees C. Although the onset of inhibition during the assay is slow and dependent upon Vi concentration (kapp approximately 0.3 M-1 s-1), the final level of inhibition approaches 100%, provided the Vi concentration is in slight excess over the concentration of ATPase sites. Inhibition is not reversible by dialysis or the addition of reducing agents. The source of this irreversible inhibition consists of the formation of a stable, inactive complex with the composition M . ADP . Vi (where M represents a single myosin active site). The complex has been isolated, and its mechanism of formation from M, ADP, and Vi has been studied. Omission of ATP increases the rate of formation by about 35-fold (kapp approximately 11 M-1 s-1), yet this rate is still low in comparison with the rates of simple protein-ligand association reactions. This slowness is interpreted in terms of a rate-limited isomerization step that follows the association of M+, ADP, and Vi: M+ . ADP . Vi leads to M+. ADP . Vi (+ indicates the inactive product of the isomerization). The properties of M.ADP.Vi are compared with those of the ATPase intermediate M**.ADP . Pi, and the possible role of Vi as an analog of Pi is discussed."} {"id": "PMID:156924", "title": "Morphine potentiation of tonic immobility: effects of naloxone, PCPA, and 5,6-DHT.", "content": "The duration of tonic immobility in chickens, a catatonic-like state produced by brief restraint, was greatly potentiated by a single 1.0 mg/kg injection of morphine. Naloxone by itself, however, had no effect on tonic immobility, and only an exceptionally large dose of naloxone blocked the morphine potentiation. Pretreatment with PCPA and 5,6-dihydroxytryptamine completely eliminated the morphine enhancement. The effect of morphine on tonic immobility may be mediated by a central serotonergic-raphe system.", "contents": "Morphine potentiation of tonic immobility: effects of naloxone, PCPA, and 5,6-DHT. The duration of tonic immobility in chickens, a catatonic-like state produced by brief restraint, was greatly potentiated by a single 1.0 mg/kg injection of morphine. Naloxone by itself, however, had no effect on tonic immobility, and only an exceptionally large dose of naloxone blocked the morphine potentiation. Pretreatment with PCPA and 5,6-dihydroxytryptamine completely eliminated the morphine enhancement. The effect of morphine on tonic immobility may be mediated by a central serotonergic-raphe system."} {"id": "PMID:156923", "title": "Defective splicing of mitochondrial rRNA in cytochrome-deficient nuclear mutants of Neurospora crassa.", "content": "Recent studies have shown that the gene encoding the large (25 S) mitochondrial rRNA of Neurospora crassa contains an intervening sequence of 2-2.5 kilobases that is not present in the mature 25S mitochondrial rRNA. Earlier studies had provided evidence that mitochondrial rRNAs in Neurospora are synthesized via a 32S precursor RNA that contains sequences for both the mature 19S and 25S RNA species. The present work shows that the intervening sequence is not present in 32S RNA. However, we have identified two temperature-sensitive nuclear mutants that fail to excise the intervening sequence at the nonpermissive temperature (37 degrees C). When grown at 37 degrees C, the mutants show decreased ratios of 25S to 19S RNA and accumulate a novel 35S RNA that appears to consist of 25S RNA plus most or all of the intervening sequence. The mutants are allelic but can be distinguished in temperature shift-up experiments, mitochondrial rRNA processing turning off more rapidly in one than in the other. These mutants should provide powerful new tools for studying RNA processing in eukaryotic cells.", "contents": "Defective splicing of mitochondrial rRNA in cytochrome-deficient nuclear mutants of Neurospora crassa. Recent studies have shown that the gene encoding the large (25 S) mitochondrial rRNA of Neurospora crassa contains an intervening sequence of 2-2.5 kilobases that is not present in the mature 25S mitochondrial rRNA. Earlier studies had provided evidence that mitochondrial rRNAs in Neurospora are synthesized via a 32S precursor RNA that contains sequences for both the mature 19S and 25S RNA species. The present work shows that the intervening sequence is not present in 32S RNA. However, we have identified two temperature-sensitive nuclear mutants that fail to excise the intervening sequence at the nonpermissive temperature (37 degrees C). When grown at 37 degrees C, the mutants show decreased ratios of 25S to 19S RNA and accumulate a novel 35S RNA that appears to consist of 25S RNA plus most or all of the intervening sequence. The mutants are allelic but can be distinguished in temperature shift-up experiments, mitochondrial rRNA processing turning off more rapidly in one than in the other. These mutants should provide powerful new tools for studying RNA processing in eukaryotic cells."} {"id": "PMID:156925", "title": "Brain serotonin metabolism with relation to the head twitches elicited by lithium in combination with reserpine in mice.", "content": "Lithium alone, which scarcely induced head twitches, did not affect brain 5-hydroxytryptamine (5-HT) levels but increased 5-hydroxyindoleacetic acid (5-HIAA) levels. However, the combined use of lithium chloride (2 mEq/kg x 5, SC) and reserpine (5 mg/kg, SC) administered hourly markedly elicited the head twitches, together with the pronounced decrease of 5-HT levels and increase of 5-HIAA levels as similarly seen by reserpine alone. Pretreatment with p-chlorophenylalanine (PCPA) strongly potentiated the twitches elicited by the combined administration of lithium and reserpine, along with inducing the significant decrease of 5-HT levels and no change of 5-HIAA levels as compared with those levels in the PCPA-treated mice. The results imply that lithium produces the head twitches in the presence of reserpine, and an increase of 5-HIAA or a decrease of 5-HT levels do not necessarily interfere with the incidence of the twitches, and that the receptor sensitivity to 5-HT is strongly involved in the incidence of the head twitches.", "contents": "Brain serotonin metabolism with relation to the head twitches elicited by lithium in combination with reserpine in mice. Lithium alone, which scarcely induced head twitches, did not affect brain 5-hydroxytryptamine (5-HT) levels but increased 5-hydroxyindoleacetic acid (5-HIAA) levels. However, the combined use of lithium chloride (2 mEq/kg x 5, SC) and reserpine (5 mg/kg, SC) administered hourly markedly elicited the head twitches, together with the pronounced decrease of 5-HT levels and increase of 5-HIAA levels as similarly seen by reserpine alone. Pretreatment with p-chlorophenylalanine (PCPA) strongly potentiated the twitches elicited by the combined administration of lithium and reserpine, along with inducing the significant decrease of 5-HT levels and no change of 5-HIAA levels as compared with those levels in the PCPA-treated mice. The results imply that lithium produces the head twitches in the presence of reserpine, and an increase of 5-HIAA or a decrease of 5-HT levels do not necessarily interfere with the incidence of the twitches, and that the receptor sensitivity to 5-HT is strongly involved in the incidence of the head twitches."} {"id": "PMID:156926", "title": "Facilitation of avoidance acquisition in rats produced by P-chlorophenylalanine or P-chloroamphetamine.", "content": "The effects of reducing brain serotonin using p-chlorophenylalanine (PCPA) were examined as a follow up to our previous report that reducing serotonin with p-chloroamphetamine (PCA) facilitated Y-maze avoidance acquisition and reduced open field activity. In the current work, PCPA was also found to facilitate Y-maze avoidance acquisition, while open field activity, although reduced, was not reduced significantly. In a second experiment, we re-examined PCA, except that the apparatus was changed in order to test the generality of the effect of PCA on avoidance performance in a task other than the Y-maze. Testing was also run at varying shock intensities to determine if this was a significant determinant of the effect. PCA reliably facilitated shuttle-box avoidance acquisition and did so at all shock intensities tested. Finally, in a third experiment, the time course of the onset of the PCA-induced avoidance facilitation was examined and found to develop 8--10 hours following drug treatment and not at a shorter drug to test interval of 4 hours. The present data, in conjunction with our previous data support the concept that lowered brain serotonin content facilitates avoidance acquisition regardless of the specific method used to reduce serotonin or to assess avoidance acquisition.", "contents": "Facilitation of avoidance acquisition in rats produced by P-chlorophenylalanine or P-chloroamphetamine. The effects of reducing brain serotonin using p-chlorophenylalanine (PCPA) were examined as a follow up to our previous report that reducing serotonin with p-chloroamphetamine (PCA) facilitated Y-maze avoidance acquisition and reduced open field activity. In the current work, PCPA was also found to facilitate Y-maze avoidance acquisition, while open field activity, although reduced, was not reduced significantly. In a second experiment, we re-examined PCA, except that the apparatus was changed in order to test the generality of the effect of PCA on avoidance performance in a task other than the Y-maze. Testing was also run at varying shock intensities to determine if this was a significant determinant of the effect. PCA reliably facilitated shuttle-box avoidance acquisition and did so at all shock intensities tested. Finally, in a third experiment, the time course of the onset of the PCA-induced avoidance facilitation was examined and found to develop 8--10 hours following drug treatment and not at a shorter drug to test interval of 4 hours. The present data, in conjunction with our previous data support the concept that lowered brain serotonin content facilitates avoidance acquisition regardless of the specific method used to reduce serotonin or to assess avoidance acquisition."} {"id": "PMID:156927", "title": "Surgery and postsurgical management of the patient with low back pain.", "content": "The role of surgery in the care of back pain and sciatica is discussed. Surgery's role in this case is relatively minor considering the overall problems of back disorders. The history, signs, and symptoms of various diagnostic categories are reviewed. Factors in deciding on the need for surgical care are analyzed. An algorithm that displays the diagnostic approach as well as various treatment plans helps in the decision-making process. Various exercise programs for postsurgical care are outlined. Details of the surgical procedures are also presented to explain the degree of tissue damage created by surgery itself.", "contents": "Surgery and postsurgical management of the patient with low back pain. The role of surgery in the care of back pain and sciatica is discussed. Surgery's role in this case is relatively minor considering the overall problems of back disorders. The history, signs, and symptoms of various diagnostic categories are reviewed. Factors in deciding on the need for surgical care are analyzed. An algorithm that displays the diagnostic approach as well as various treatment plans helps in the decision-making process. Various exercise programs for postsurgical care are outlined. Details of the surgical procedures are also presented to explain the degree of tissue damage created by surgery itself."} {"id": "PMID:156928", "title": "Clinical anatomy of the lumbosacral complex.", "content": "The clinical anatomy of the lumbosacral region has been presented to show the complexity of spinal pathology. Individual structures are described, but emphasis is placed on understanding the concept of the entire functional unit and how alteration can lead to pain and disability.", "contents": "Clinical anatomy of the lumbosacral complex. The clinical anatomy of the lumbosacral region has been presented to show the complexity of spinal pathology. Individual structures are described, but emphasis is placed on understanding the concept of the entire functional unit and how alteration can lead to pain and disability."} {"id": "PMID:156929", "title": "Physical examination of the lumbosacral complex.", "content": "Examination is the foundation upon which effective treatment rests. The importance of a methodical step-by-step process is stressed. The manner in which the examination findings are used to assess the efficacy of the treatment techniques is illustrated. This paper outlines one method of examining the lumbosacral complex.", "contents": "Physical examination of the lumbosacral complex. Examination is the foundation upon which effective treatment rests. The importance of a methodical step-by-step process is stressed. The manner in which the examination findings are used to assess the efficacy of the treatment techniques is illustrated. This paper outlines one method of examining the lumbosacral complex."} {"id": "PMID:156930", "title": "Mobilization of the spine.", "content": "This article presents spinal dysfunction (as opposed to disease) as being an altered state of mechanics demonstrating either an aberrant motion or an increase or decrease from the expected range. Examination techniques, including passive intervertebral motion testing, are outlined, as is the grading system for recording results. Mobilizations and positional distraction are advocated for treating restricted range, and the neurophysiological and mechanical effects are explained along with their indications and contraindications. Pain is presented as a misleading symptom that cannot be relied upon to monitor the results of treatment. The author considers that exercise routines have no place in the treatment of spinal dysfunction, although selected exercises may be given for the patient's particular requirements. Walking is advocated to maintain mobility and function, but running, cycling, and swimming are generally discouraged.", "contents": "Mobilization of the spine. This article presents spinal dysfunction (as opposed to disease) as being an altered state of mechanics demonstrating either an aberrant motion or an increase or decrease from the expected range. Examination techniques, including passive intervertebral motion testing, are outlined, as is the grading system for recording results. Mobilizations and positional distraction are advocated for treating restricted range, and the neurophysiological and mechanical effects are explained along with their indications and contraindications. Pain is presented as a misleading symptom that cannot be relied upon to monitor the results of treatment. The author considers that exercise routines have no place in the treatment of spinal dysfunction, although selected exercises may be given for the patient's particular requirements. Walking is advocated to maintain mobility and function, but running, cycling, and swimming are generally discouraged."} {"id": "PMID:156931", "title": "An innovative program for the restoration of patients with chronic back pain.", "content": "The literature on conventional medical procedures for restoring high-risk patients having chronic low back pain reveals that these procedures are ineffective and may even be iatrogenic. An alternative, noninvasive approach, which takes into consideration the critical role of cognitive and emotional factors, is practiced at Casa Colina Hospital for Rehabilitative Medicine. Details of the approach as well as comments confirming its efficacy are presented.", "contents": "An innovative program for the restoration of patients with chronic back pain. The literature on conventional medical procedures for restoring high-risk patients having chronic low back pain reveals that these procedures are ineffective and may even be iatrogenic. An alternative, noninvasive approach, which takes into consideration the critical role of cognitive and emotional factors, is practiced at Casa Colina Hospital for Rehabilitative Medicine. Details of the approach as well as comments confirming its efficacy are presented."} {"id": "PMID:156932", "title": "Plasma insulin, carbohydrate, and free fatty acid changes in newly born infants of diabetic and non-diabetic mothers after loading with glucose, fructose, and galactose.", "content": "Changes in the concentration of blood glucose, fructose and galactose and their disappearance rate, concentration of plasma insulin, free fatty acids, blood lactate and pyruvate after intravenous glucose, fructose and galactose loads (1 g/kg) were studied in 23 infants of insulin treated diabetic mothers (IDM). The control group consisted of 42 infants of healthy mothers (IHM). The disappearance rate of these monosaccharides was higher in IDM that in IHM (P less than 0.01). All monosaccharides enhanced plasma insulin levels, but the plasma insulin concentration varied considerably. The highest insulin response with difference between IDM and IHM occurred after loading with glucose. Fructose was the least effective insulin stimulator which did not increase glucose levels. All monosaccharides decreased free fatty acid levels. Lactate levels and lactate:pyruvate ratio in IHM were increased after fructose loading. The results of this study suggest that galactose is of some physiological importance for maintaining glucose levels and that the islet apparatus of newborns of diabetic mothers is less loaded with galactose than with glucose.", "contents": "Plasma insulin, carbohydrate, and free fatty acid changes in newly born infants of diabetic and non-diabetic mothers after loading with glucose, fructose, and galactose. Changes in the concentration of blood glucose, fructose and galactose and their disappearance rate, concentration of plasma insulin, free fatty acids, blood lactate and pyruvate after intravenous glucose, fructose and galactose loads (1 g/kg) were studied in 23 infants of insulin treated diabetic mothers (IDM). The control group consisted of 42 infants of healthy mothers (IHM). The disappearance rate of these monosaccharides was higher in IDM that in IHM (P less than 0.01). All monosaccharides enhanced plasma insulin levels, but the plasma insulin concentration varied considerably. The highest insulin response with difference between IDM and IHM occurred after loading with glucose. Fructose was the least effective insulin stimulator which did not increase glucose levels. All monosaccharides decreased free fatty acid levels. Lactate levels and lactate:pyruvate ratio in IHM were increased after fructose loading. The results of this study suggest that galactose is of some physiological importance for maintaining glucose levels and that the islet apparatus of newborns of diabetic mothers is less loaded with galactose than with glucose."} {"id": "PMID:156933", "title": "Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection.", "content": "The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.", "contents": "Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy."} {"id": "PMID:156934", "title": "A study of the effect of dietary factors and various exercises on the swimming performance of the albino rat.", "content": "In Experiment 1 a double-phase test diet (high-protein low-carbohydrate phase (HP): 5 days, high-carbohydrate phase (HC): 2 days) was compared to a normal diet by measuring all-out performance in rats trained by steady or interval swimming exercise. The tests carried out on the 8th day showed the swimming performance to be improved to a similar extent by the two training procedures, to be further improved by the test diet in the exercised animals; changes in liver glycogen, blood glucose and serum corticosterone reflected especially in the influence of exercise which in some cases was potentiated by the test diet. In Experiment 2 the 5 days of high protein intake were treated separately from the effect of the double-phase test diet as a whole in order to study the mechanism. These aminals were exercised by treadmill running of 7 days. Cytochrome P450 content of the liver rose under the effect of exercise as well as the HP phase, thus supplying additional evidence for the enzyme inducer effect of physical exertion. Glycogen decreased both in the muscle and liver during the HP phase and returned to normal after the HC phase. Liver glycogen rose to an even higher level than normal in the trained groups, but muscle glycogen values remained lower, this may be related to the shortness of training and to an accelerated rate of turnover. High protein intake associated with a depletion of carbohydrate stores was found to have an effect of its own which, when followed by replenishment of calories reserves, might be used to advantage in improving physical performance.", "contents": "A study of the effect of dietary factors and various exercises on the swimming performance of the albino rat. In Experiment 1 a double-phase test diet (high-protein low-carbohydrate phase (HP): 5 days, high-carbohydrate phase (HC): 2 days) was compared to a normal diet by measuring all-out performance in rats trained by steady or interval swimming exercise. The tests carried out on the 8th day showed the swimming performance to be improved to a similar extent by the two training procedures, to be further improved by the test diet in the exercised animals; changes in liver glycogen, blood glucose and serum corticosterone reflected especially in the influence of exercise which in some cases was potentiated by the test diet. In Experiment 2 the 5 days of high protein intake were treated separately from the effect of the double-phase test diet as a whole in order to study the mechanism. These aminals were exercised by treadmill running of 7 days. Cytochrome P450 content of the liver rose under the effect of exercise as well as the HP phase, thus supplying additional evidence for the enzyme inducer effect of physical exertion. Glycogen decreased both in the muscle and liver during the HP phase and returned to normal after the HC phase. Liver glycogen rose to an even higher level than normal in the trained groups, but muscle glycogen values remained lower, this may be related to the shortness of training and to an accelerated rate of turnover. High protein intake associated with a depletion of carbohydrate stores was found to have an effect of its own which, when followed by replenishment of calories reserves, might be used to advantage in improving physical performance."} {"id": "PMID:156935", "title": "Inactivation of bradykinin by placental peptidases.", "content": "Normal human placental eluate (0.15 M NaCl) has very high capacity for inactivating synthetic bradykinin (its specific activity is 20--50 times higher than that of normal human serum). In chromatography on DEAE-Sephadex A 50, several fractions with bradykinin-inactivating capacity were recovered. On Cbo-Phe-Arg synthetic substrate, one fraction with kininase activity was identified as carboxypeptidase N. This is not identical with serum (pregnancy) carboxypeptidase N and does not therefore pass into the blood stream. The properties of other fractions with kininase activity were studied. Aminopeptidase activity degrading L-lysine-p-nitranilide and L-arginine-beta-naphthylamide was separate from kininase activity.", "contents": "Inactivation of bradykinin by placental peptidases. Normal human placental eluate (0.15 M NaCl) has very high capacity for inactivating synthetic bradykinin (its specific activity is 20--50 times higher than that of normal human serum). In chromatography on DEAE-Sephadex A 50, several fractions with bradykinin-inactivating capacity were recovered. On Cbo-Phe-Arg synthetic substrate, one fraction with kininase activity was identified as carboxypeptidase N. This is not identical with serum (pregnancy) carboxypeptidase N and does not therefore pass into the blood stream. The properties of other fractions with kininase activity were studied. Aminopeptidase activity degrading L-lysine-p-nitranilide and L-arginine-beta-naphthylamide was separate from kininase activity."} {"id": "PMID:156936", "title": "Use of the periodogram in the analysis of high frequency basal blood sugar oscillations in healthy subjects.", "content": "Twenty-four triplicate samples of the morning blood sugar of 17 fasting healthy women were taken from the cubital vein with a cannula at 15-sec intervals. The mean value was 4.44+/-0.69 mmol/l and the mean variation range 22.4+/-9.2%. Variability within the sets of three samples was 1.7+/-0.9%. In 23.5% of the cases, statistically significant periodicities (p less than 0.05) were detected by computing the periodogram. In 29.4%, several periodic components (2--4) were detected simultaneously. After deducting harmonic components, the residual scatter fell by an average 43.9%. In four cases the drop was significant in the F test at 1% and in one case at 5% level. The periodic components of the observed oscillations could be due to oscillation in feedback control circuits and the main role in the random component was evidently played by inadequate glucose blending in the circulation.", "contents": "Use of the periodogram in the analysis of high frequency basal blood sugar oscillations in healthy subjects. Twenty-four triplicate samples of the morning blood sugar of 17 fasting healthy women were taken from the cubital vein with a cannula at 15-sec intervals. The mean value was 4.44+/-0.69 mmol/l and the mean variation range 22.4+/-9.2%. Variability within the sets of three samples was 1.7+/-0.9%. In 23.5% of the cases, statistically significant periodicities (p less than 0.05) were detected by computing the periodogram. In 29.4%, several periodic components (2--4) were detected simultaneously. After deducting harmonic components, the residual scatter fell by an average 43.9%. In four cases the drop was significant in the F test at 1% and in one case at 5% level. The periodic components of the observed oscillations could be due to oscillation in feedback control circuits and the main role in the random component was evidently played by inadequate glucose blending in the circulation."} {"id": "PMID:156939", "title": "[Modification of the ovarian cycle, ovulation and reproduction in rat by administration of p-chlorophenylalanine in the pre and post ovulation period (author's transl)].", "content": "The effect of p-Chlorophenylalanine (PCPA) administered in pre and post-ovulation phases on ovulation reproduction and ovarian cycle was studied in rats. Vaginal smears, number of ovules, mature follicles and ovaric histologic features were evaluated. PCPA administered in the periods after follicular rupture prolongs the diestrus phase from 2 to 10 consecutive days and totally inhibits the reproductive conduct. When administered in the periods just prior to follicular rupture, PCPA prolongs the estrus phase from 2 to 4 consecutive days and does not totally inhibit reproduction. A progressive increase in reproduction took place as treatment time approached ovulation, to such an extent that the number of inseminated and fertilized rats when treated at the ninth hour of the proestrus phase, was superior to the control group. PCPA administered in periods after and before follicular rupture totally inhibits ovulation in all cases. Ovaries present many mature follicles, as many as in the controls sacrificed at the 18 hour of the proestrus, just before ovulation.", "contents": "[Modification of the ovarian cycle, ovulation and reproduction in rat by administration of p-chlorophenylalanine in the pre and post ovulation period (author's transl)]. The effect of p-Chlorophenylalanine (PCPA) administered in pre and post-ovulation phases on ovulation reproduction and ovarian cycle was studied in rats. Vaginal smears, number of ovules, mature follicles and ovaric histologic features were evaluated. PCPA administered in the periods after follicular rupture prolongs the diestrus phase from 2 to 10 consecutive days and totally inhibits the reproductive conduct. When administered in the periods just prior to follicular rupture, PCPA prolongs the estrus phase from 2 to 4 consecutive days and does not totally inhibit reproduction. A progressive increase in reproduction took place as treatment time approached ovulation, to such an extent that the number of inseminated and fertilized rats when treated at the ninth hour of the proestrus phase, was superior to the control group. PCPA administered in periods after and before follicular rupture totally inhibits ovulation in all cases. Ovaries present many mature follicles, as many as in the controls sacrificed at the 18 hour of the proestrus, just before ovulation."} {"id": "PMID:156940", "title": "[Supression by copulation of the inhibitory effect of p-chlorophenylalanine on rat ovulation (author's transl)].", "content": "The effect of copulating on reflex ovulation was studied in rat. The effect of PCPA (300 mg/kg, i.p.) on ovulation and reproduction was compared by evaluating number of oocytes in tubes, histologic features of ovaries, vaginal cycle, insemination, fertilization and number of embryos per rat. PCPA, administered on 9th and 16th h of the estrus phase, totally inhibits ovulation, stimulates reproductive behaviour and prolongs the estrogenic phase. When the animals are kept in copulatory conditions for 16 or 46 hours, the inhibition induced in ovulation disappears to the extent that 60% of the rats become pregnant though the number of embryos is under that of the control group. The farther the treatment with PCPA within the same cycle in the ovulatory period, the greater the inhibitory effect on ovulation is and the lesser the neutralizing effect produced by reflexes related to copulation. Administration of PCPA at the 16 hour of the diestrus causes a greater increase in the average number of embryos-as compared to administration at the 9 hour. In periods longer than 48 hours before ovulation, the inhibition brought about by PCPA is not suppressed by copulatory conditions kept for 16 or 24 hours and is only neutralized if they are kept during a complete cycle. Those treated with PCPA in the diestrus phase and maintained in copulatory conditions for 46 hours, present a higher average of embryos than those maintained in similar conditions for 16 hours.", "contents": "[Supression by copulation of the inhibitory effect of p-chlorophenylalanine on rat ovulation (author's transl)]. The effect of copulating on reflex ovulation was studied in rat. The effect of PCPA (300 mg/kg, i.p.) on ovulation and reproduction was compared by evaluating number of oocytes in tubes, histologic features of ovaries, vaginal cycle, insemination, fertilization and number of embryos per rat. PCPA, administered on 9th and 16th h of the estrus phase, totally inhibits ovulation, stimulates reproductive behaviour and prolongs the estrogenic phase. When the animals are kept in copulatory conditions for 16 or 46 hours, the inhibition induced in ovulation disappears to the extent that 60% of the rats become pregnant though the number of embryos is under that of the control group. The farther the treatment with PCPA within the same cycle in the ovulatory period, the greater the inhibitory effect on ovulation is and the lesser the neutralizing effect produced by reflexes related to copulation. Administration of PCPA at the 16 hour of the diestrus causes a greater increase in the average number of embryos-as compared to administration at the 9 hour. In periods longer than 48 hours before ovulation, the inhibition brought about by PCPA is not suppressed by copulatory conditions kept for 16 or 24 hours and is only neutralized if they are kept during a complete cycle. Those treated with PCPA in the diestrus phase and maintained in copulatory conditions for 46 hours, present a higher average of embryos than those maintained in similar conditions for 16 hours."} {"id": "PMID:156942", "title": "[Transportable communication and environmental control device for the profoundly handicapped (author's transl)].", "content": "At the centre for the physically handicapped in Weingarten/W\u00fcrttemberg (Federal Republic of Germany) a multidisciplinary approach has been made to develop a experimental model of a communication device for the profoundly handicapped, which is transportable and can easily be handled and adapted to motor and cognitive abilities. This tool is available free of charge for a test period after which the user is required to give a report of his experiences, which will provide the basis for models which will be marketed.", "contents": "[Transportable communication and environmental control device for the profoundly handicapped (author's transl)]. At the centre for the physically handicapped in Weingarten/W\u00fcrttemberg (Federal Republic of Germany) a multidisciplinary approach has been made to develop a experimental model of a communication device for the profoundly handicapped, which is transportable and can easily be handled and adapted to motor and cognitive abilities. This tool is available free of charge for a test period after which the user is required to give a report of his experiences, which will provide the basis for models which will be marketed."} {"id": "PMID:156946", "title": "Restimulation in secondary MLC by autologous non-T cells.", "content": "Lymphocytes sensitized in mixed leucocyte culture (MLC) were restimulated with non-T or complete cells. Cells primed against autologous non-T cells and restimulated with autologous cells gave responses with the kinetics of a secondary response. In contrast, cells primed against either type of autologous cell responded to restimulation by allogeneic cells with the kinetics of a primary MLC response. Following priming against alloantigens good secondary responses against both complete and non-T allogeneic restimulators were seen. Restimulation with autologous non-T cells, but not autologous complete cells, also led to secondary responses. The observation of different responses to antigens expressed on non-T autologous lymphocytes, in comparison to complete cells, implies that the secondary MLC involves more than response against alloantigens. Allogeneic and autologous MLC may be qualitatively different phenomena, the latter representing the recognition of identifying structures between interacting populations of cooperating cells.", "contents": "Restimulation in secondary MLC by autologous non-T cells. Lymphocytes sensitized in mixed leucocyte culture (MLC) were restimulated with non-T or complete cells. Cells primed against autologous non-T cells and restimulated with autologous cells gave responses with the kinetics of a secondary response. In contrast, cells primed against either type of autologous cell responded to restimulation by allogeneic cells with the kinetics of a primary MLC response. Following priming against alloantigens good secondary responses against both complete and non-T allogeneic restimulators were seen. Restimulation with autologous non-T cells, but not autologous complete cells, also led to secondary responses. The observation of different responses to antigens expressed on non-T autologous lymphocytes, in comparison to complete cells, implies that the secondary MLC involves more than response against alloantigens. Allogeneic and autologous MLC may be qualitatively different phenomena, the latter representing the recognition of identifying structures between interacting populations of cooperating cells."} {"id": "PMID:156947", "title": "Human leucocyte interferon: analysis of effect on MLC and effector cell generation.", "content": "Mixed lymphocyte cultures (MLC) showed decreased thymidine incorporation when interferon (IF) had been added to the culture medium. The cell-mediated lympholysis (CML) potential generated in mixed lymphocyte cultures grown in the presence of IF was substantially augmented at a certain concentration range. Highly purified leucocyte IF also had this effect, whereas mock preparations did not. The CML-augmenting property was found in the antiviral fraction after separation of semipurified leucocyte IF (by the method of Dahl & Degree). The possibility that the effects were due to a shift in kinetics after culturing in the presence of IF has been excluded. The killer-enhancing properties of IF did not seem to be due to an enhanced expression of histocompatibility antigens, the selective inhibition of CML suppressor cells, or a change in the specificity of recognized target cells. The results of secondary in vitro MLC-CML experiments, in which primary MLC had been carried out in the presence or absence of IF, indicated that the compound acts (in vitro) through preferential selection of cells that are less sensitive to inhibition by IF and more likely to kill.", "contents": "Human leucocyte interferon: analysis of effect on MLC and effector cell generation. Mixed lymphocyte cultures (MLC) showed decreased thymidine incorporation when interferon (IF) had been added to the culture medium. The cell-mediated lympholysis (CML) potential generated in mixed lymphocyte cultures grown in the presence of IF was substantially augmented at a certain concentration range. Highly purified leucocyte IF also had this effect, whereas mock preparations did not. The CML-augmenting property was found in the antiviral fraction after separation of semipurified leucocyte IF (by the method of Dahl & Degree). The possibility that the effects were due to a shift in kinetics after culturing in the presence of IF has been excluded. The killer-enhancing properties of IF did not seem to be due to an enhanced expression of histocompatibility antigens, the selective inhibition of CML suppressor cells, or a change in the specificity of recognized target cells. The results of secondary in vitro MLC-CML experiments, in which primary MLC had been carried out in the presence or absence of IF, indicated that the compound acts (in vitro) through preferential selection of cells that are less sensitive to inhibition by IF and more likely to kill."} {"id": "PMID:156948", "title": "Activation of abdominal muscles during some physiotherapeutic exercises.", "content": "The aim was to evaluate the theoretical efficiency of some abdominal muscle exercises for strength training. Sit-up with rounded back (curl-up) from the supine position up to 45 degrees activates the straight and oblique abdominal muscles to 50% of the values for maximum isometric contraction measured as integrated EMG. This exercise was compared with two previously suggested exercises: curl-up with simultaneous activation of the plantar-flexors of the ankle activated the abdominal muscles to the same level and curl-up from a position with dorsally extended spine did not activate the muscles more. Curl-up with lateral rotation of the trunk gave a high activation of the oblique muscles. This exercise was compared with two completely isometric exercises suggested for patients with back pain: only somewhat lower activation was obtained during an exercise in supine position with lateral resistance to the knees, but with lateral resistance against the elevated forearms there was only little activation.", "contents": "Activation of abdominal muscles during some physiotherapeutic exercises. The aim was to evaluate the theoretical efficiency of some abdominal muscle exercises for strength training. Sit-up with rounded back (curl-up) from the supine position up to 45 degrees activates the straight and oblique abdominal muscles to 50% of the values for maximum isometric contraction measured as integrated EMG. This exercise was compared with two previously suggested exercises: curl-up with simultaneous activation of the plantar-flexors of the ankle activated the abdominal muscles to the same level and curl-up from a position with dorsally extended spine did not activate the muscles more. Curl-up with lateral rotation of the trunk gave a high activation of the oblique muscles. This exercise was compared with two completely isometric exercises suggested for patients with back pain: only somewhat lower activation was obtained during an exercise in supine position with lateral resistance to the knees, but with lateral resistance against the elevated forearms there was only little activation."} {"id": "PMID:156962", "title": "A cytogenetic study of a mentally retarded population in South Africa.", "content": "The entire population of the Umgeni Waterfall Institution for mentally retarded Whites was karyotyped using aceto-orcein and ASG banded preparations. Of the 512 subjects, 376 were males and 136 were females. Their ages ranged from 1 to 72 years and mental retardation ranged from borderline to profound. Altogether 11,1% had chromosome abnormalities, of which 8,2% had trisomy-21, 1,9% had other autosome abnormalities, and sex chromosome anomalies occurred in 1%. Normal variant chromosomes were seen in 4,5% of the population. Problems that arose in the course of the survey were mainly due to inadequate family histories and the high proportion of cases in which contact with the family had been lost, thus precluding proper follow-up studies.", "contents": "A cytogenetic study of a mentally retarded population in South Africa. The entire population of the Umgeni Waterfall Institution for mentally retarded Whites was karyotyped using aceto-orcein and ASG banded preparations. Of the 512 subjects, 376 were males and 136 were females. Their ages ranged from 1 to 72 years and mental retardation ranged from borderline to profound. Altogether 11,1% had chromosome abnormalities, of which 8,2% had trisomy-21, 1,9% had other autosome abnormalities, and sex chromosome anomalies occurred in 1%. Normal variant chromosomes were seen in 4,5% of the population. Problems that arose in the course of the survey were mainly due to inadequate family histories and the high proportion of cases in which contact with the family had been lost, thus precluding proper follow-up studies."} {"id": "PMID:156963", "title": "Chromosome abnormalities in South African mental retardates.", "content": "Standard and differential staining techniques were employed in this cytogenetic study of mentally retarded Whites at the Umgeni Waterfall Institution. All of the 512 patients were karyotyped and 57 were found to have chromosome abnormalities. Of these, 42 had trisomy-21; there were 3 subjects with 5p deletion (cri-du-chat) syndrome, 3 had supernumerary small marker chromosomes, and 2 had complex structural rearrangements. Gonosomal aneuploidies were less common than the autosomal defects and only 2 poly-X males and 1 poly-X female were identified. Long Y chromosomes were found in 11 males and 4 others had deleted Y chromosomes. One abnormal chromosome, a deletion of the terminal region of 11q, was missed in unbanded karyotypes. Banding is essential to the identification of structurally abnormal chromosomes.", "contents": "Chromosome abnormalities in South African mental retardates. Standard and differential staining techniques were employed in this cytogenetic study of mentally retarded Whites at the Umgeni Waterfall Institution. All of the 512 patients were karyotyped and 57 were found to have chromosome abnormalities. Of these, 42 had trisomy-21; there were 3 subjects with 5p deletion (cri-du-chat) syndrome, 3 had supernumerary small marker chromosomes, and 2 had complex structural rearrangements. Gonosomal aneuploidies were less common than the autosomal defects and only 2 poly-X males and 1 poly-X female were identified. Long Y chromosomes were found in 11 males and 4 others had deleted Y chromosomes. One abnormal chromosome, a deletion of the terminal region of 11q, was missed in unbanded karyotypes. Banding is essential to the identification of structurally abnormal chromosomes."} {"id": "PMID:156965", "title": "Resistance and sphincter-like properties of the cystic duct.", "content": "The canine cystic duct, like that in man, has an extremely thin layer of muscle deep to the mucosal layer, surrounded by a dense layer of collagen fibers. The resistance to flow through the duct was studied in 16 anesthetized dogs by perfusing the duct with saline solution at constant pressure and recording the flow rate of the solution. The flow rate varied with respiratory movements, but there were also nonrespiratory variations which might be due to spontaneous sphincter-like contractions. Significant reductions in flow through the duct followed systemic intravenous or local intra-arterial injections of morphine or pharmacologic concentrations of adrenaline or cholecystokinin. It was concluded that an extremely small amount of muscle in the wall of the duct was capable of sphincter-like activity. The resistances to flow were the same in either direction through the duct, an indication that the prominent mucosal folds, valves of Heister, did not function as unidirectional valves. In view of the high resistance to flow through the duct and the possibility that sphincter-like activity may also occur under physiologic conditions, the function of the duct requires more attention than it has received in the past.", "contents": "Resistance and sphincter-like properties of the cystic duct. The canine cystic duct, like that in man, has an extremely thin layer of muscle deep to the mucosal layer, surrounded by a dense layer of collagen fibers. The resistance to flow through the duct was studied in 16 anesthetized dogs by perfusing the duct with saline solution at constant pressure and recording the flow rate of the solution. The flow rate varied with respiratory movements, but there were also nonrespiratory variations which might be due to spontaneous sphincter-like contractions. Significant reductions in flow through the duct followed systemic intravenous or local intra-arterial injections of morphine or pharmacologic concentrations of adrenaline or cholecystokinin. It was concluded that an extremely small amount of muscle in the wall of the duct was capable of sphincter-like activity. The resistances to flow were the same in either direction through the duct, an indication that the prominent mucosal folds, valves of Heister, did not function as unidirectional valves. In view of the high resistance to flow through the duct and the possibility that sphincter-like activity may also occur under physiologic conditions, the function of the duct requires more attention than it has received in the past."} {"id": "PMID:156966", "title": "Noninvasive hemodynamic evaluation in selection of amputation level.", "content": "Various noninvasive techniques of hemodynamic evaluation have been used to determine the optimal level of amputation. Noninvasively obtained measurements of pressure and blood flow in the lower extremity have been found to be reliable in predicting the probable healing of an amputation. In patients with severely calcified noncompressible arteries, noninvasive electromagnetic flowmeter measurements of peak pulsatile flow provide a more accurate indication of the vascular status of the patient than do blood pressure measurements which, in such patients, frequently exceed 300 millimeters of mercury. Skin thermistor thermometry does not appear to be applicable in patients with extensive severe ischemia of the leg. The need for a reliable method of determining the lowest possible level of amputation is well recognized. Such factors as wound edge bleeding and clinical judgment too often lead to above the knee amputation when, frequently, a more distal amputation could have been possible. Our experience has shown that noninvasive techniques for hemodynamic evaluation are a valuable aid to clinical judgment in determining accurately the lowest level for successful limb amputation.", "contents": "Noninvasive hemodynamic evaluation in selection of amputation level. Various noninvasive techniques of hemodynamic evaluation have been used to determine the optimal level of amputation. Noninvasively obtained measurements of pressure and blood flow in the lower extremity have been found to be reliable in predicting the probable healing of an amputation. In patients with severely calcified noncompressible arteries, noninvasive electromagnetic flowmeter measurements of peak pulsatile flow provide a more accurate indication of the vascular status of the patient than do blood pressure measurements which, in such patients, frequently exceed 300 millimeters of mercury. Skin thermistor thermometry does not appear to be applicable in patients with extensive severe ischemia of the leg. The need for a reliable method of determining the lowest possible level of amputation is well recognized. Such factors as wound edge bleeding and clinical judgment too often lead to above the knee amputation when, frequently, a more distal amputation could have been possible. Our experience has shown that noninvasive techniques for hemodynamic evaluation are a valuable aid to clinical judgment in determining accurately the lowest level for successful limb amputation."} {"id": "PMID:156967", "title": "Macrophage-related suppressor cells in human renal transplant recipients.", "content": "In this study 66 renal transplant recipients were studied by in vitro immunologic monitoring assays in an attempt to delineate some immune reactivity parameters which migh explain the successful long-term survival of HLA incompatible allografts. Ninety percent of the recipients were found to be responsive to their specific donors in one-way mixed lymphocyte culture assays, indicating the presence of antigen reactive proliferating T cells. In contrast, studies of the in vitro generation of cytotoxic T cells showed that 73% of the long-term recipients demonstrated a marked hyporesponsiveness to the donor in cell-mediated lympholysis (CML) assays. Longitudinal studies indicated that specific CML hyporesponsiveness to the donor developed after transplantion. In the majority of recipients, CML hyporesponsiveness could be related to a suppressor cell phenomenon, since recipient mononuculear cells specifically suppressed the CML reactivity of third-party cells to the donor. Recipient CML hyporesponsiveness to the donor could be abrogated by removal of recipient adherent cells, most of which were monocytes or macrophages. The suppressor cell effect on CML is postulated to be related to macrophages which are either acting independently or under the regulation of suppressor T cells. These studies are among the first to suggest that suppressor cell regulation of relevant effector T cell activity may be important in the facilitation of successful human renal transplantation.", "contents": "Macrophage-related suppressor cells in human renal transplant recipients. In this study 66 renal transplant recipients were studied by in vitro immunologic monitoring assays in an attempt to delineate some immune reactivity parameters which migh explain the successful long-term survival of HLA incompatible allografts. Ninety percent of the recipients were found to be responsive to their specific donors in one-way mixed lymphocyte culture assays, indicating the presence of antigen reactive proliferating T cells. In contrast, studies of the in vitro generation of cytotoxic T cells showed that 73% of the long-term recipients demonstrated a marked hyporesponsiveness to the donor in cell-mediated lympholysis (CML) assays. Longitudinal studies indicated that specific CML hyporesponsiveness to the donor developed after transplantion. In the majority of recipients, CML hyporesponsiveness could be related to a suppressor cell phenomenon, since recipient mononuculear cells specifically suppressed the CML reactivity of third-party cells to the donor. Recipient CML hyporesponsiveness to the donor could be abrogated by removal of recipient adherent cells, most of which were monocytes or macrophages. The suppressor cell effect on CML is postulated to be related to macrophages which are either acting independently or under the regulation of suppressor T cells. These studies are among the first to suggest that suppressor cell regulation of relevant effector T cell activity may be important in the facilitation of successful human renal transplantation."} {"id": "PMID:156969", "title": "The RhLA complex of rhesus monkeys. XI: Positive MLC reactions between identical sibs caused by alloimmunization.", "content": "D-locus identical pairs of monkeys were alloimmunized. An exchange of skin and blood between initially MLC-negative unrelated monkeys frequently led to strong mutual reactivity in mixed cultures. This was not the case when RhLA identical siblings were similarly (mutually) immunized. These data led to the postulation of a second RhLA-linked MLC locus, named D', which exerts its influence only after alloimmunization. Interestingly, strong MLC responsiveness between the RhLA identical siblings could be provoked after further immunization with tissue from a thired party animal. This unexpected MLC-reactivity is ascribed to the in fluence of minor non MHC linked loci which express themselves if the responder has been sensitized against a disparate D'-product. It is suggested that the postulated D' locus has a \"helper function\" in that it assists in triggering proliferative responses in mixed cultures against the products of these non MHC loci.", "contents": "The RhLA complex of rhesus monkeys. XI: Positive MLC reactions between identical sibs caused by alloimmunization. D-locus identical pairs of monkeys were alloimmunized. An exchange of skin and blood between initially MLC-negative unrelated monkeys frequently led to strong mutual reactivity in mixed cultures. This was not the case when RhLA identical siblings were similarly (mutually) immunized. These data led to the postulation of a second RhLA-linked MLC locus, named D', which exerts its influence only after alloimmunization. Interestingly, strong MLC responsiveness between the RhLA identical siblings could be provoked after further immunization with tissue from a thired party animal. This unexpected MLC-reactivity is ascribed to the in fluence of minor non MHC linked loci which express themselves if the responder has been sensitized against a disparate D'-product. It is suggested that the postulated D' locus has a \"helper function\" in that it assists in triggering proliferative responses in mixed cultures against the products of these non MHC loci."} {"id": "PMID:156970", "title": "Different stimulating capacity of monocytes and B lymphocytes in mixed leukocyte cultures: a dose response study.", "content": "Cell fractions highly enriched either for monocytes of for B lymphocytes were separated from human peripheral blood. They were tested for their capacity to stimulate allogeneic lymphocytes in mixed leukocyte cultures, using dose-response titrations. Neither population could be stimulated to proliferate by allogeneic cells, but both proved strong stimulators. In this respect monocytes were more efficient than B cell preparations. Differences were pronounced at the lower numbers of stimulating cells but were no longer significant with large amounts of cells.", "contents": "Different stimulating capacity of monocytes and B lymphocytes in mixed leukocyte cultures: a dose response study. Cell fractions highly enriched either for monocytes of for B lymphocytes were separated from human peripheral blood. They were tested for their capacity to stimulate allogeneic lymphocytes in mixed leukocyte cultures, using dose-response titrations. Neither population could be stimulated to proliferate by allogeneic cells, but both proved strong stimulators. In this respect monocytes were more efficient than B cell preparations. Differences were pronounced at the lower numbers of stimulating cells but were no longer significant with large amounts of cells."} {"id": "PMID:156971", "title": "Aromatization of androgens by human breast cancer.", "content": "The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed.", "contents": "Aromatization of androgens by human breast cancer. The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed."} {"id": "PMID:156972", "title": "Changes in mixed lymphocyte culture-reactive lymphocytes following alloimmunization of single lymph nodes in sheep.", "content": "When an \"isolated\" single lymph node is challenged with irradiated allogeneic lymphocytes, there is a change in the reactivity of the lymphocytes flowing out of the node when they are cultured in vitro in unidirectional mixed lymphocyte cultures (MLC) against the immunizing lymphocytes. These changes in the reactivity of the recipient lymphocytes are shortlived, follow a set time sequence in relation to the cell traffic changes accompanying the immune response, are the property of small lymphocytes and not blast cells, are exhibited by surface Ig-negative cells, and they are specific for the donor lymphocytes. It is suggested that antigen causes the selective retention of antigen-specific lymphocytes within the stimulated node followed by the proliferation and differentiation of large numbers of antigen-specific cells, which then leave the lymph node as small lymphocytes.", "contents": "Changes in mixed lymphocyte culture-reactive lymphocytes following alloimmunization of single lymph nodes in sheep. When an \"isolated\" single lymph node is challenged with irradiated allogeneic lymphocytes, there is a change in the reactivity of the lymphocytes flowing out of the node when they are cultured in vitro in unidirectional mixed lymphocyte cultures (MLC) against the immunizing lymphocytes. These changes in the reactivity of the recipient lymphocytes are shortlived, follow a set time sequence in relation to the cell traffic changes accompanying the immune response, are the property of small lymphocytes and not blast cells, are exhibited by surface Ig-negative cells, and they are specific for the donor lymphocytes. It is suggested that antigen causes the selective retention of antigen-specific lymphocytes within the stimulated node followed by the proliferation and differentiation of large numbers of antigen-specific cells, which then leave the lymph node as small lymphocytes."} {"id": "PMID:156978", "title": "Atopy.", "content": "Atopy should be considered an immunological disorder that may result in several clinical conditions including respiratory disease, allergic dermatitis, food allergy dermatitis, and perhaps flea allergy dermatitis. The clinical course of the disease tends to fluctuate from season to season, which makes objective evaluation of injection therapy difficult. The disease is subject to both familial and environmental influences, and dogs maintain the atopic state throughout their life. The disease cannot be cured; however, a combination of symptomatic and specific injection therapy usually provides adequate control of the clinical signs. Owners of atopic dogs should appreciate that their pet has inherently itching skin, a cure for which is unlikely to be found.", "contents": "Atopy. Atopy should be considered an immunological disorder that may result in several clinical conditions including respiratory disease, allergic dermatitis, food allergy dermatitis, and perhaps flea allergy dermatitis. The clinical course of the disease tends to fluctuate from season to season, which makes objective evaluation of injection therapy difficult. The disease is subject to both familial and environmental influences, and dogs maintain the atopic state throughout their life. The disease cannot be cured; however, a combination of symptomatic and specific injection therapy usually provides adequate control of the clinical signs. Owners of atopic dogs should appreciate that their pet has inherently itching skin, a cure for which is unlikely to be found."} {"id": "PMID:156981", "title": "[Protein and lipid metabolic characteristics of persons in a hot climate].", "content": "A comparative investigation of the total protein, its fractions, total lipids, cholesterol, carotinoids, retinol, tocopherol in the blood serum of practically healthy persons (donors) was effected in different periods of the year. The proteinic and lipids metabolism rates in persons residing in conditions of a hot climate were found to change substantially, depending upon the season of the years. It is possible that, to a certain degree, this is due to a change in the nature of the nutritional pattern of these people under the effect of climate factors.", "contents": "[Protein and lipid metabolic characteristics of persons in a hot climate]. A comparative investigation of the total protein, its fractions, total lipids, cholesterol, carotinoids, retinol, tocopherol in the blood serum of practically healthy persons (donors) was effected in different periods of the year. The proteinic and lipids metabolism rates in persons residing in conditions of a hot climate were found to change substantially, depending upon the season of the years. It is possible that, to a certain degree, this is due to a change in the nature of the nutritional pattern of these people under the effect of climate factors."} {"id": "PMID:156983", "title": "[Properties of the influenza viruses isolated in 1976 from gulls in Astrakhan Province].", "content": "Investigation of a number of properties of influenza viruses isolated from Laridae birds in the Astrakhan region showed that in one epizootic focus avian influenza viruses with different hemagglutinins and identical neuraminidase may circulate among Laridae birds. Among viruses with the antigenic formula Hav5Nav2 clear-cut differences in virulence and plaque-forming capacity were demonstrated.", "contents": "[Properties of the influenza viruses isolated in 1976 from gulls in Astrakhan Province]. Investigation of a number of properties of influenza viruses isolated from Laridae birds in the Astrakhan region showed that in one epizootic focus avian influenza viruses with different hemagglutinins and identical neuraminidase may circulate among Laridae birds. Among viruses with the antigenic formula Hav5Nav2 clear-cut differences in virulence and plaque-forming capacity were demonstrated."} {"id": "PMID:156984", "title": "[Virological and serological examination of the patients in a period of influenza A1 outbreak in Aktyubinsk].", "content": "In October--December, 1977, an epidemic outbreak of influenza predominantly among young people of an organized community was recorded in Aktyubinsk. For decifering the outbreak virological and serological examinations of 325 subjects in foci of the disease as well as hospitalized patients were carried out. The etiology of influenza was confirmed clinically, epidemiologically, and by laboratory examinations in 150 patients. In chick embryos, 53 strains of influenza A1 virus were isolated. Investigations of the strains causing the influenza outbreak in autumn 1977 confirmed that they were influenza A (HINI) viruses. Antihemagglutinating antibodies to the new influenza A1 virus isolate were demonstrated in patients and normal subjects. A detailed analysis of antibody levels to 5 serotypes of influenza virus revealed a rise in antibody titers to the homologous serotypes A2 and to the new A1 isolate. In the acute stage of the disease and in convalescence the geometric mean antibody titer to the new A1 isolate was comparatively lower than to other serotypes.", "contents": "[Virological and serological examination of the patients in a period of influenza A1 outbreak in Aktyubinsk]. In October--December, 1977, an epidemic outbreak of influenza predominantly among young people of an organized community was recorded in Aktyubinsk. For decifering the outbreak virological and serological examinations of 325 subjects in foci of the disease as well as hospitalized patients were carried out. The etiology of influenza was confirmed clinically, epidemiologically, and by laboratory examinations in 150 patients. In chick embryos, 53 strains of influenza A1 virus were isolated. Investigations of the strains causing the influenza outbreak in autumn 1977 confirmed that they were influenza A (HINI) viruses. Antihemagglutinating antibodies to the new influenza A1 virus isolate were demonstrated in patients and normal subjects. A detailed analysis of antibody levels to 5 serotypes of influenza virus revealed a rise in antibody titers to the homologous serotypes A2 and to the new A1 isolate. In the acute stage of the disease and in convalescence the geometric mean antibody titer to the new A1 isolate was comparatively lower than to other serotypes."} {"id": "PMID:156985", "title": "[Chim virus, a new arbovirus isolated from ixodid and argasid ticks collected in the burrows of great gerbils on the territory of the Uzbek SSR].", "content": "Five strains of hitherto unknown arbovirus designated Chim by the place of primary collection of ticks was isolated from Ixodid and Argasid ticks collected in the Uzbek SSR in burrows of great gerbils. The virus has no antigenic relationships with arboviruses previously isolated from ticks, its size varies from 100 to 220 nm, it contains RNA and has a lipid-containing envelope. Chim virus is pathogenic only for suckling mice by the intracerebral route and exerts cytopathic effect in continuous L, Rh, BHK cell lines.", "contents": "[Chim virus, a new arbovirus isolated from ixodid and argasid ticks collected in the burrows of great gerbils on the territory of the Uzbek SSR]. Five strains of hitherto unknown arbovirus designated Chim by the place of primary collection of ticks was isolated from Ixodid and Argasid ticks collected in the Uzbek SSR in burrows of great gerbils. The virus has no antigenic relationships with arboviruses previously isolated from ticks, its size varies from 100 to 220 nm, it contains RNA and has a lipid-containing envelope. Chim virus is pathogenic only for suckling mice by the intracerebral route and exerts cytopathic effect in continuous L, Rh, BHK cell lines."} {"id": "PMID:156991", "title": "[Left ventricular relaxation and filling abnormalities in patients with HOCM and left ventricular pressure overload (author's transl)].", "content": "In order to test the hypothesis that delayed mitral valve opening (MO) with regard to endsystolic dimension (t DS-MO) is specific for hypertrophic obstructive cardiomyopathy (HOCM), LV echograms of patients with different forms of LV hypertrophy due to chronic pressure overload (CPO; aortic stenosis + arterial hypertension, n = 24) and hypertrophic obstructive cardiomyopathy (n = 24) were recorded, digitized and compared with those of normals (N :n = 28(. In patients with HOCM (93 +/- 37 ms; p less than 0.0001) and CPO (66 +/- 31 ms; p less than 0.0001) the time t DS-MO was significantly delayed compared with N (13 +/- 15 MS), due to abnormal relaxation. This prolonged relaxation time resulted in an abnormal diameter increase (delta D) during the isovolumic relaxation phase (HOCM: 4.0 +/- 2.2 MM/CPO: 3.0 +/- 1.8 mm; p less than 0.0001/N:0.6 +/- 0.5 mm) and the rapid filling phase (HOCM 7.6 +/- 2.7 mm; p less than 0.0001/CPO 9.2 +/- 2.9 mm; p less than 0.05 / N: 10.7 +/- 2.2 mm). The echocardiographical signs of an abnormal relaxation are not specific for HOCM, they can be seen in different forms of secondary LV hypertrophy and are accompanied by changes in the diastolic filling pattern.", "contents": "[Left ventricular relaxation and filling abnormalities in patients with HOCM and left ventricular pressure overload (author's transl)]. In order to test the hypothesis that delayed mitral valve opening (MO) with regard to endsystolic dimension (t DS-MO) is specific for hypertrophic obstructive cardiomyopathy (HOCM), LV echograms of patients with different forms of LV hypertrophy due to chronic pressure overload (CPO; aortic stenosis + arterial hypertension, n = 24) and hypertrophic obstructive cardiomyopathy (n = 24) were recorded, digitized and compared with those of normals (N :n = 28(. In patients with HOCM (93 +/- 37 ms; p less than 0.0001) and CPO (66 +/- 31 ms; p less than 0.0001) the time t DS-MO was significantly delayed compared with N (13 +/- 15 MS), due to abnormal relaxation. This prolonged relaxation time resulted in an abnormal diameter increase (delta D) during the isovolumic relaxation phase (HOCM: 4.0 +/- 2.2 MM/CPO: 3.0 +/- 1.8 mm; p less than 0.0001/N:0.6 +/- 0.5 mm) and the rapid filling phase (HOCM 7.6 +/- 2.7 mm; p less than 0.0001/CPO 9.2 +/- 2.9 mm; p less than 0.05 / N: 10.7 +/- 2.2 mm). The echocardiographical signs of an abnormal relaxation are not specific for HOCM, they can be seen in different forms of secondary LV hypertrophy and are accompanied by changes in the diastolic filling pattern."} {"id": "PMID:156992", "title": "[A model analysis on the effects of left ventricular hypertrophy and dilatation on pump function and myocardial force and shortening (author's transl)].", "content": "The effects of hypertrophy and dilatation on myocardial force and shortening were analysed using Wong's formula for equatorial midwall stress in a thick-walled ellipsoid of revolution. Wall thickness, chamber volume and ejection fraction were treated as independent variables. An isolated increase in wall thickness reduces wall stress and, to a lesser extent, myocardial fiber shortening, i.e. myocardial function is overestimated from ventricular pressures and ejection fraction. Ventricular dilatation without a proportional increase in myocardial mass leads to an increase of myocardial force and shortening, i.e. myocardial performance is underestimated from ventricular function. A decrease of ejection fraction increases total systolic myocardial force considerably, leading to a shift to the right on the inverse relation of force and shortening. Therefore the efficiency of myocardial contraction is reduced and myocardial performance is better than ventricular pump function would indicate.", "contents": "[A model analysis on the effects of left ventricular hypertrophy and dilatation on pump function and myocardial force and shortening (author's transl)]. The effects of hypertrophy and dilatation on myocardial force and shortening were analysed using Wong's formula for equatorial midwall stress in a thick-walled ellipsoid of revolution. Wall thickness, chamber volume and ejection fraction were treated as independent variables. An isolated increase in wall thickness reduces wall stress and, to a lesser extent, myocardial fiber shortening, i.e. myocardial function is overestimated from ventricular pressures and ejection fraction. Ventricular dilatation without a proportional increase in myocardial mass leads to an increase of myocardial force and shortening, i.e. myocardial performance is underestimated from ventricular function. A decrease of ejection fraction increases total systolic myocardial force considerably, leading to a shift to the right on the inverse relation of force and shortening. Therefore the efficiency of myocardial contraction is reduced and myocardial performance is better than ventricular pump function would indicate."} {"id": "PMID:156993", "title": "[Echocardiographic diagnosis of subpulmonic obstruction in hypertrophic cardiomyopathy (a case report) (author's transl)].", "content": "The echocardiogram of a patient presenting with a systolic ejection murmur and ECG evidence of left ventricular hypertrophy revealed asymmetric septal hypertrophy but no abnormal systolic anterior motion of the mitral valve as in IHSS. Her pulmonary echo disclosed small A waves, partial valve closure in early systole and coarse systolic fluttering. This motion pattern--which is similar to that of patients with infundibular pulmonary stenosis and which resembles the aortic valve motion pattern in discrete subaortic stenosis--led us to the diagnosis of hypertrophic cardiomyopathy with subpulmonic obstruction, which was later confirmed by cardiac catheterization.", "contents": "[Echocardiographic diagnosis of subpulmonic obstruction in hypertrophic cardiomyopathy (a case report) (author's transl)]. The echocardiogram of a patient presenting with a systolic ejection murmur and ECG evidence of left ventricular hypertrophy revealed asymmetric septal hypertrophy but no abnormal systolic anterior motion of the mitral valve as in IHSS. Her pulmonary echo disclosed small A waves, partial valve closure in early systole and coarse systolic fluttering. This motion pattern--which is similar to that of patients with infundibular pulmonary stenosis and which resembles the aortic valve motion pattern in discrete subaortic stenosis--led us to the diagnosis of hypertrophic cardiomyopathy with subpulmonic obstruction, which was later confirmed by cardiac catheterization."} {"id": "PMID:156994", "title": "Amanitin content and toxicity of Amantia verna Bull.", "content": "The alpha-, beta-, and gamma-amanitin content of 11 samples of Amanita verna Bull., collected during 1975--1978 in Germany and Switzerland, has been determined by high performance thin-layer chromatography (HPTLC) of crude methanolic extracts. The toxicity (i. v. LD50 for mice of defatted, lyophilized, methanolic extracts) of 3 samples has been compared with that of A. phalloides from the same site of collection. The amanitin content of A. verna ranged from 2250 to 4570 mg/kg dry weight; the fungi contained almost as much beta- as alpha-amanitin, whereas the gamma-amanitin content amounted to about 12% of the total amanitin. A verna contained less amanitin (65% on the average) than A. phalloides from the same collection site, but it was not significantly less toxic, since the phallotoxins contributed to the toxicity of either species in our tests.", "contents": "Amanitin content and toxicity of Amantia verna Bull. The alpha-, beta-, and gamma-amanitin content of 11 samples of Amanita verna Bull., collected during 1975--1978 in Germany and Switzerland, has been determined by high performance thin-layer chromatography (HPTLC) of crude methanolic extracts. The toxicity (i. v. LD50 for mice of defatted, lyophilized, methanolic extracts) of 3 samples has been compared with that of A. phalloides from the same site of collection. The amanitin content of A. verna ranged from 2250 to 4570 mg/kg dry weight; the fungi contained almost as much beta- as alpha-amanitin, whereas the gamma-amanitin content amounted to about 12% of the total amanitin. A verna contained less amanitin (65% on the average) than A. phalloides from the same collection site, but it was not significantly less toxic, since the phallotoxins contributed to the toxicity of either species in our tests."} {"id": "PMID:156995", "title": "[Absorption, body distribution, metabolism, and excretion of dieldrin in non-human primates and other laboratory animals (author's transl)].", "content": "Using 14C-labelled dieldrin, the resorption, body distribution, and rate of excretion as well as the metabolism was investigated qualitatively and quantitatively. The experiments with mice, rats, rabbits, Rhesus monkeys, and chimpanzees were performed under identical conditions to obtain reliably comparable results.", "contents": "[Absorption, body distribution, metabolism, and excretion of dieldrin in non-human primates and other laboratory animals (author's transl)]. Using 14C-labelled dieldrin, the resorption, body distribution, and rate of excretion as well as the metabolism was investigated qualitatively and quantitatively. The experiments with mice, rats, rabbits, Rhesus monkeys, and chimpanzees were performed under identical conditions to obtain reliably comparable results."} {"id": "PMID:156997", "title": "A 1H NMR study of the syn-anti dynamic equilibrium in adenine nucleosides and nucleotides with the aid of some synthetic model analogues with fixed conformations.", "content": "The syn-anti equilibrium about the glycosidic bond in adenosine and some related analogues was studied by means of 1H NMR spectroscopy, with the aid of several model analogues fixed in given conformations either by intramolecular bonding, or by introduction of a bulky substituent. A model unambiguously and exclusively in the syn conformation is 8- (alpha-hydroxyisopropyl) adenosine; while one fixed in the anti conformation is 8,5'-anhydro-8-oxoadenosine. A new analogue, fixed in the high anti conformation, is 8,2-'O-isopropylidenearabinofuranosyladenine. Several additional new model compounds were synthesized and their properties are described. With the aid of these models, the syn-anti dynamic equilibrium was examined for adenosine and some related compounds in different solvent systems, and the conformer populations evaluated quantitatively. The validity of the procedure applied, and the accuracy of the results are critically examined, and compared with findings obtained by other procedures. Available literature data on the syn-anti equilibrium in other 8-substituted adenosines are re-analyzed in the light of the present results. An analysis is also presented of the interdependence of the various conformational parameter, i. e. conformation about the glycosidic bond and those of the sugar ring and exocyclic carbinol group, in adenosine and 2',3'-O-isopropylidenadenosine.", "contents": "A 1H NMR study of the syn-anti dynamic equilibrium in adenine nucleosides and nucleotides with the aid of some synthetic model analogues with fixed conformations. The syn-anti equilibrium about the glycosidic bond in adenosine and some related analogues was studied by means of 1H NMR spectroscopy, with the aid of several model analogues fixed in given conformations either by intramolecular bonding, or by introduction of a bulky substituent. A model unambiguously and exclusively in the syn conformation is 8- (alpha-hydroxyisopropyl) adenosine; while one fixed in the anti conformation is 8,5'-anhydro-8-oxoadenosine. A new analogue, fixed in the high anti conformation, is 8,2-'O-isopropylidenearabinofuranosyladenine. Several additional new model compounds were synthesized and their properties are described. With the aid of these models, the syn-anti dynamic equilibrium was examined for adenosine and some related compounds in different solvent systems, and the conformer populations evaluated quantitatively. The validity of the procedure applied, and the accuracy of the results are critically examined, and compared with findings obtained by other procedures. Available literature data on the syn-anti equilibrium in other 8-substituted adenosines are re-analyzed in the light of the present results. An analysis is also presented of the interdependence of the various conformational parameter, i. e. conformation about the glycosidic bond and those of the sugar ring and exocyclic carbinol group, in adenosine and 2',3'-O-isopropylidenadenosine."} {"id": "PMID:156999", "title": "Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography.", "content": "Two S-adenosyl-L-methionine:furanocoumarin O-methyltransferases of R. graveolens, acting at the 5- and 8-hydroxyl of the psoralen nucleus, were completely resolved by adsorption on a general affinity ligand, 5-(3-carboxypropanamido) xanthotoxin, followed by specific desorption by bergaptol and xanthotoxol, respectively. The 5-O-methyltransferase was purified 450-fold by this procedure, the 8-O-methyltransferase 112-fold, and both enzyme fractions were electrophoretically homogeneous. No resolution could be achieved of the activity against two 5-hydroxypsoralens or of the activity against two 8-hydroxypsoralens, and conclusive evidence is presented for the existence of only one 5-O-methyltransferase and only one 8-O-methyltransferase acting on linear furanocoumarins.", "contents": "Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Two S-adenosyl-L-methionine:furanocoumarin O-methyltransferases of R. graveolens, acting at the 5- and 8-hydroxyl of the psoralen nucleus, were completely resolved by adsorption on a general affinity ligand, 5-(3-carboxypropanamido) xanthotoxin, followed by specific desorption by bergaptol and xanthotoxol, respectively. The 5-O-methyltransferase was purified 450-fold by this procedure, the 8-O-methyltransferase 112-fold, and both enzyme fractions were electrophoretically homogeneous. No resolution could be achieved of the activity against two 5-hydroxypsoralens or of the activity against two 8-hydroxypsoralens, and conclusive evidence is presented for the existence of only one 5-O-methyltransferase and only one 8-O-methyltransferase acting on linear furanocoumarins."} {"id": "PMID:156996", "title": "Improved synthesis and rapid isolation millimole quantities of adenylysulfate.", "content": "An improved enzymatic method for the synthesis of adenylysulfate (APS) from adenosine 5'-phosphate using APS-reductase from Thiobacillus denitrificans is described. Isolation of millimole quantitities of this sulfur nucleotide is achieved rapidly by means of ion exchange chromatography on a strongly basic ion exchange resin. A facile and reproducible desalting procedure is described.", "contents": "Improved synthesis and rapid isolation millimole quantities of adenylysulfate. An improved enzymatic method for the synthesis of adenylysulfate (APS) from adenosine 5'-phosphate using APS-reductase from Thiobacillus denitrificans is described. Isolation of millimole quantitities of this sulfur nucleotide is achieved rapidly by means of ion exchange chromatography on a strongly basic ion exchange resin. A facile and reproducible desalting procedure is described."} {"id": "PMID:157000", "title": "Drug-protein interaction: 8-methoxy psoralen as photosensitizer of enzymes and amino acids.", "content": "For a better insight of the molecular basis of the photobiological effects of furocoumarins, the relevance of proteins oxydation by singlet oxygen produced by these substrates under irradiation with long u. v. light was studied. Complex oligomeric as well as simple monomeric purified enzymes with high or low molecular weight and different properties and simple amino acids were irradiated under oxygen in presence of 8-methoxy-psoralen. The effects on both proteins and amino acids were compared with those obtained under similar conditions with typical photosensitizers as methylene blue and Rose Bengal. The results indicated that the photooxydation of proteins, although possible, appears to play a minor role, if any, in the mechanism of action of furocoumarin.", "contents": "Drug-protein interaction: 8-methoxy psoralen as photosensitizer of enzymes and amino acids. For a better insight of the molecular basis of the photobiological effects of furocoumarins, the relevance of proteins oxydation by singlet oxygen produced by these substrates under irradiation with long u. v. light was studied. Complex oligomeric as well as simple monomeric purified enzymes with high or low molecular weight and different properties and simple amino acids were irradiated under oxygen in presence of 8-methoxy-psoralen. The effects on both proteins and amino acids were compared with those obtained under similar conditions with typical photosensitizers as methylene blue and Rose Bengal. The results indicated that the photooxydation of proteins, although possible, appears to play a minor role, if any, in the mechanism of action of furocoumarin."} {"id": "PMID:157001", "title": "Action of citrinin on liposomes.", "content": "Citrinin, a mycotoxin, was studied for its effect on artificial membranes (liposomes). Of the three (net positive, negative and neural) liposomal preparations tested, the membrane carrying a net positive charge was preferentially acted upon by citrinin and in this case even the lowest concentration was found to be sufficient for causing a high degree of damage. This is the first report of evidence that citrinin has a direct effect on membranes. It was shown to exhibit concentration dependency in its lytic activity on artificial membranes leading to leaching of trapped 45Ca2% ions.", "contents": "Action of citrinin on liposomes. Citrinin, a mycotoxin, was studied for its effect on artificial membranes (liposomes). Of the three (net positive, negative and neural) liposomal preparations tested, the membrane carrying a net positive charge was preferentially acted upon by citrinin and in this case even the lowest concentration was found to be sufficient for causing a high degree of damage. This is the first report of evidence that citrinin has a direct effect on membranes. It was shown to exhibit concentration dependency in its lytic activity on artificial membranes leading to leaching of trapped 45Ca2% ions."} {"id": "PMID:156998", "title": "Comparative studies on the dodecameric and hexameric forms of yeast aminopeptidase I.", "content": "Yeast aminopeptidase I, when purified from autolysates of brewer's yeast, is obtained in two molecular froms a) the enzymatically active dodecameric complex (Mr = 640,000, s20,w = 22 S) and b) inactive hexamers (Mr = 320,000, s20,w = 12 S). Although the amino acid composition of the 12 S protein is very similar to that of the active enzyme,the hexamers behave differently in ionic exchange chromatography and during electrophoresis on polyacrylamide gels. Moreover, the antigenic properties of 12 S and 22 S aminopeptidase forms suggest a considerable degree of structural diversity. Several strains of Saccharomyces cerevisiae did not contain hexameric forms although their 22 S aminopeptidase was immunologically indistinguishable from brewer's yeast aminopeptidase. It is proposed that the hexameric protein is the result of \"unproductive\" aggregation of aminopeptidase subunits.", "contents": "Comparative studies on the dodecameric and hexameric forms of yeast aminopeptidase I. Yeast aminopeptidase I, when purified from autolysates of brewer's yeast, is obtained in two molecular froms a) the enzymatically active dodecameric complex (Mr = 640,000, s20,w = 22 S) and b) inactive hexamers (Mr = 320,000, s20,w = 12 S). Although the amino acid composition of the 12 S protein is very similar to that of the active enzyme,the hexamers behave differently in ionic exchange chromatography and during electrophoresis on polyacrylamide gels. Moreover, the antigenic properties of 12 S and 22 S aminopeptidase forms suggest a considerable degree of structural diversity. Several strains of Saccharomyces cerevisiae did not contain hexameric forms although their 22 S aminopeptidase was immunologically indistinguishable from brewer's yeast aminopeptidase. It is proposed that the hexameric protein is the result of \"unproductive\" aggregation of aminopeptidase subunits."} {"id": "PMID:157003", "title": "[Sequence complexity of transcribed unique DNA sequences in genome of mouse P815 mastocytoma cells (author's transl)].", "content": "The sequence complexity of nuclear RNA from mouse liver, mouse spleen and highly malignant P815 mastocytoma was measured by nRNA driven hybridization to unique DNA sequences of P815 cells. The unique DNA sequences represent 63% of the total nuclear DNA of P815 cells and their availibility in hybridization experiments was found to be 76%. Of these sequences 7.8% formed hybrids with nuclear RNA of this cell, about 11.5% with mouse spleen and about 14.5% with mouse liver nuclear RNA. Assuming an asymmetrical transcription, the complexities of these transcripts are 2.8 X 10(8) nucleotides for mouse P815 mastocytomas, 4.3 X 10(8) for mouse spleen and about 5.3 X 10(8) nucleotides for mouse liver. Cellular specifity of the transcribed information was analyzed in additivity experiments, in which unique DNA sequences, not complementary to the nuclear RNA of one cell were annealed to the nuclear RNAs of the two other tissues/cells. In these experiments most of the nuclear RNA sequences of P815 cells were found to be also present in the nucleus of mouse liver and spleen. Only a small portion of the unique DNA sequences of P815 mastocytoma (about 1.2% corresponding to 4.4 X 10(7) nucleotides) was found to be complementary only to P815 mastocytoma nuclear RNA.", "contents": "[Sequence complexity of transcribed unique DNA sequences in genome of mouse P815 mastocytoma cells (author's transl)]. The sequence complexity of nuclear RNA from mouse liver, mouse spleen and highly malignant P815 mastocytoma was measured by nRNA driven hybridization to unique DNA sequences of P815 cells. The unique DNA sequences represent 63% of the total nuclear DNA of P815 cells and their availibility in hybridization experiments was found to be 76%. Of these sequences 7.8% formed hybrids with nuclear RNA of this cell, about 11.5% with mouse spleen and about 14.5% with mouse liver nuclear RNA. Assuming an asymmetrical transcription, the complexities of these transcripts are 2.8 X 10(8) nucleotides for mouse P815 mastocytomas, 4.3 X 10(8) for mouse spleen and about 5.3 X 10(8) nucleotides for mouse liver. Cellular specifity of the transcribed information was analyzed in additivity experiments, in which unique DNA sequences, not complementary to the nuclear RNA of one cell were annealed to the nuclear RNAs of the two other tissues/cells. In these experiments most of the nuclear RNA sequences of P815 cells were found to be also present in the nucleus of mouse liver and spleen. Only a small portion of the unique DNA sequences of P815 mastocytoma (about 1.2% corresponding to 4.4 X 10(7) nucleotides) was found to be complementary only to P815 mastocytoma nuclear RNA."} {"id": "PMID:157002", "title": "Effect of mechanical traumatization on rate and constancy of oxygen uptake of isolated diaphragms.", "content": "Diaphragms of mice were traumatized by division parallel or transversally to the muscle fibres. The extent of traumatization was varied by the degree of subdivision. Oxygen uptake was measured by the Warburg technique. Undivided diaphragms as control displayed constant oxygen uptake for the four hours of observation. With divided diaphragms oxygen uptake was unstable. Division parallel to the muscle fibres resulted in continuous decrease of oxygen uptake after a normal initial phase; the decline was significantly steeper was increasing extent of traumatization. Division transversally to the muscle fibres resulted in an initial increase of oxygen uptake followed in a second phase by a continuous decrease. The initial increase as well as the final decrease of oxygen uptake was more pronounced with higher extent of subdivision.", "contents": "Effect of mechanical traumatization on rate and constancy of oxygen uptake of isolated diaphragms. Diaphragms of mice were traumatized by division parallel or transversally to the muscle fibres. The extent of traumatization was varied by the degree of subdivision. Oxygen uptake was measured by the Warburg technique. Undivided diaphragms as control displayed constant oxygen uptake for the four hours of observation. With divided diaphragms oxygen uptake was unstable. Division parallel to the muscle fibres resulted in continuous decrease of oxygen uptake after a normal initial phase; the decline was significantly steeper was increasing extent of traumatization. Division transversally to the muscle fibres resulted in an initial increase of oxygen uptake followed in a second phase by a continuous decrease. The initial increase as well as the final decrease of oxygen uptake was more pronounced with higher extent of subdivision."} {"id": "PMID:157005", "title": "The influence of spermine, spermidine and various sera on T-lymphocyte and granulocyte colony growth in vitro.", "content": "Using T-lymphocyte (T-LC) and granulocyte colony (GC) assays with truly proliferating cells, the dose-response relationships of spermine and spermidine, fetal calf (FCS), calf (CS), horse (HS) and human AB serum (ABS), and of the polyamines in the presence of selected does of the sera were analyzed. In contrast to earlier observations using [3H]thymidine uptake masurements it was found that the polyamines as well as the sera themselves inhibit T-LC and GC growth in the presence of autologous HS and ABS, respectively. The polyamines also inhibit in the presence of additional HS and ABS, yet most effectively with added FCS and CS. Thus the previously reported species-specificity of the serum-dependent polyamine inhibition has here been shown to be more quantitative than qualitative. These studies stress the significance of assays utilizing truly dividing cells and broad dose-response relationship in order to assess specific biological effects in vitro.", "contents": "The influence of spermine, spermidine and various sera on T-lymphocyte and granulocyte colony growth in vitro. Using T-lymphocyte (T-LC) and granulocyte colony (GC) assays with truly proliferating cells, the dose-response relationships of spermine and spermidine, fetal calf (FCS), calf (CS), horse (HS) and human AB serum (ABS), and of the polyamines in the presence of selected does of the sera were analyzed. In contrast to earlier observations using [3H]thymidine uptake masurements it was found that the polyamines as well as the sera themselves inhibit T-LC and GC growth in the presence of autologous HS and ABS, respectively. The polyamines also inhibit in the presence of additional HS and ABS, yet most effectively with added FCS and CS. Thus the previously reported species-specificity of the serum-dependent polyamine inhibition has here been shown to be more quantitative than qualitative. These studies stress the significance of assays utilizing truly dividing cells and broad dose-response relationship in order to assess specific biological effects in vitro."} {"id": "PMID:157007", "title": "[Temperature-dependence of biological process (author's transl)].", "content": "Temperature dependence of biological processes is described by the modified Arrhenius equation, in which the constant is replaced by a temperature-variable coefficient. The theoretical foundation for this replacement is given and experimentally verified.", "contents": "[Temperature-dependence of biological process (author's transl)]. Temperature dependence of biological processes is described by the modified Arrhenius equation, in which the constant is replaced by a temperature-variable coefficient. The theoretical foundation for this replacement is given and experimentally verified."} {"id": "PMID:157006", "title": "Free-running human circadian rhythms in Svalbard.", "content": "The body temperature, activity-rest time, electrolytes of urine samples and mood was measured in two persons a 19 day period under continuous light conditions in the arctic (vicinity of Ny Alesund, Svalbard-Spitsbergen). For temperature recording a new thermoprobe and a portable printer was used. Possible week Zeitgeber of the 24 hour day did not synchronize the circadian system, since circadian rhythms of about 26 hours were found. These results open up the possibility to study effects of drugs on the circadian system of humans under Svalbard conditions.", "contents": "Free-running human circadian rhythms in Svalbard. The body temperature, activity-rest time, electrolytes of urine samples and mood was measured in two persons a 19 day period under continuous light conditions in the arctic (vicinity of Ny Alesund, Svalbard-Spitsbergen). For temperature recording a new thermoprobe and a portable printer was used. Possible week Zeitgeber of the 24 hour day did not synchronize the circadian system, since circadian rhythms of about 26 hours were found. These results open up the possibility to study effects of drugs on the circadian system of humans under Svalbard conditions."} {"id": "PMID:157008", "title": "[A fluorometic test for microsomal monooxygenase activity in the rat liver with scoparone as substrate (author's transl)].", "content": "A sensitive fluorometric test for the determination of monooxygenase activity in liver microsomes from rats is described. The assay is based on the O-demethylation of 6,7-dimethoxycoumarin (scoparone) to 7-hydroxy-6-methoxycoumarin and 6-hydroxy-7-methoxycoumarin. Pretreatment of rats with phenobarbital or polycyclic hydrocarbons (benzo[a]pyrene, 3-methylcholanthrene) causes a significant increase in the amount of microsomal dealkylation activity.", "contents": "[A fluorometic test for microsomal monooxygenase activity in the rat liver with scoparone as substrate (author's transl)]. A sensitive fluorometric test for the determination of monooxygenase activity in liver microsomes from rats is described. The assay is based on the O-demethylation of 6,7-dimethoxycoumarin (scoparone) to 7-hydroxy-6-methoxycoumarin and 6-hydroxy-7-methoxycoumarin. Pretreatment of rats with phenobarbital or polycyclic hydrocarbons (benzo[a]pyrene, 3-methylcholanthrene) causes a significant increase in the amount of microsomal dealkylation activity."} {"id": "PMID:157013", "title": "Down's syndrome in Nigeria: dermatoglyphic analysis of 50 cases.", "content": "Dermatoglyphic analysis was carried out on 50 cases of Down's Syndrome and 100 normals. It involved the digital patterns, axial triradius and palmer crease on the hands. 94.6% of the digital patterns in Down's Syndrome were the Ulnar loop type against 62.5% in the normals. No arch was reported in Down's Syndrome. There were more whorl patterns in the normals (31.1%) than in the Down's Syndrome group (4%). The mode of the distribution of the digital indices in the Down's Syndrome was at +3.58. More than 84% of the 50 cases of Down's Syndrome have digital index of +3.58 compared to only 12% in the normals.", "contents": "Down's syndrome in Nigeria: dermatoglyphic analysis of 50 cases. Dermatoglyphic analysis was carried out on 50 cases of Down's Syndrome and 100 normals. It involved the digital patterns, axial triradius and palmer crease on the hands. 94.6% of the digital patterns in Down's Syndrome were the Ulnar loop type against 62.5% in the normals. No arch was reported in Down's Syndrome. There were more whorl patterns in the normals (31.1%) than in the Down's Syndrome group (4%). The mode of the distribution of the digital indices in the Down's Syndrome was at +3.58. More than 84% of the 50 cases of Down's Syndrome have digital index of +3.58 compared to only 12% in the normals."} {"id": "PMID:157010", "title": "Some characteristics of sulphate uptake into synaptosomes.", "content": "Incorporation of Na235SO4 by ovine brain Ficoll-prepared synaptosomes were studied as a function of time, temperature and substrate concentration. The rate of uptake obeyed Michaelis-Menten kinetics and apparent Km value of 4.4 mM Na2SO4 was determined. In the presence of p-hydroxymercuribenzoate a reduction in sulphate uptake was noted which suggests that thiol groups may possibly be implicated in the uptake mechanism.", "contents": "Some characteristics of sulphate uptake into synaptosomes. Incorporation of Na235SO4 by ovine brain Ficoll-prepared synaptosomes were studied as a function of time, temperature and substrate concentration. The rate of uptake obeyed Michaelis-Menten kinetics and apparent Km value of 4.4 mM Na2SO4 was determined. In the presence of p-hydroxymercuribenzoate a reduction in sulphate uptake was noted which suggests that thiol groups may possibly be implicated in the uptake mechanism."} {"id": "PMID:157016", "title": "[Determining the cause of clicking from clinical, roentgenological, and histological results (author's transl)].", "content": "A cause of clicking is described. Results of clinical, roentgenological, and histological examinations show that clicking may be considered to be due to overstraining of the lateral ligament of the temporomandibular joint or of a muscle lying between the tuberculum articulare and the collum mandibulae, respectively. Straining is triggered by a connective-tissue and bony protuberance produced by mechanical irritation on the lateral capitulum mandibulae.", "contents": "[Determining the cause of clicking from clinical, roentgenological, and histological results (author's transl)]. A cause of clicking is described. Results of clinical, roentgenological, and histological examinations show that clicking may be considered to be due to overstraining of the lateral ligament of the temporomandibular joint or of a muscle lying between the tuberculum articulare and the collum mandibulae, respectively. Straining is triggered by a connective-tissue and bony protuberance produced by mechanical irritation on the lateral capitulum mandibulae."} {"id": "PMID:157017", "title": "[Experiences clinical tests to prove value of GRF wound dressing in the treatment of patients suffering from haemophilia (author's transl)].", "content": "Experiences are reported on the use of Gelatine-Resorcin-Formalin (GRF) wound dressing obtained in clinical tests. The treatment has been turned out to be thoroughly satisfactory in 27 cases of patients suffering from haemophilia and those suffering from Willebrand-J\u00fcrgens-Syndrome. Generally, treatment may be carried out without hospitalization of applying coagulator substituting medicaments.", "contents": "[Experiences clinical tests to prove value of GRF wound dressing in the treatment of patients suffering from haemophilia (author's transl)]. Experiences are reported on the use of Gelatine-Resorcin-Formalin (GRF) wound dressing obtained in clinical tests. The treatment has been turned out to be thoroughly satisfactory in 27 cases of patients suffering from haemophilia and those suffering from Willebrand-J\u00fcrgens-Syndrome. Generally, treatment may be carried out without hospitalization of applying coagulator substituting medicaments."} {"id": "PMID:157009", "title": "Antimicrobial activity of quaternary ammonium salts of some saturated heterocycloalkyl amines [1].", "content": "Antimicrobial activity of N-alkyl-N-dodecylpiperidinium bromides and N-ethyl-N-dodecylheterocycloalkyl ammonium bromides (pyrrolidine, morpholine, perhydroazepine) determined on grampositive and gramnegative bacteria, yeasts and moulds, presented as minimum inhibition concentration (MIC). Comparison of the effect of change of structure: lengthening of alkyl chain, change of heterocyclic ring. Change in the length of alkyl chain markedly affects the antimicrobial activity, change of heterocyclic ring has no substantial effect. The most active compounds were N-heptyl-and N-hexyl-N-dodecylpiperidinium bromides.", "contents": "Antimicrobial activity of quaternary ammonium salts of some saturated heterocycloalkyl amines [1]. Antimicrobial activity of N-alkyl-N-dodecylpiperidinium bromides and N-ethyl-N-dodecylheterocycloalkyl ammonium bromides (pyrrolidine, morpholine, perhydroazepine) determined on grampositive and gramnegative bacteria, yeasts and moulds, presented as minimum inhibition concentration (MIC). Comparison of the effect of change of structure: lengthening of alkyl chain, change of heterocyclic ring. Change in the length of alkyl chain markedly affects the antimicrobial activity, change of heterocyclic ring has no substantial effect. The most active compounds were N-heptyl-and N-hexyl-N-dodecylpiperidinium bromides."} {"id": "PMID:157018", "title": "[Results of the use of bone and cartilage transplants in maxillofacial surgery (author's transl)].", "content": "This paper reports the results of using autogenous, allogeneic, and xenogeneic bone grafts in 176 patients with maxillofacial diseases. In all, the number of complications did not exceed 5 percent. The allogeneic and xenogeneic grafts were used in the form of small chips of bone. They formed connecting and filler elements for small losses of bones without breaking the continuity of their union. In this group, the number of complications was in the region of 2.5 percent.", "contents": "[Results of the use of bone and cartilage transplants in maxillofacial surgery (author's transl)]. This paper reports the results of using autogenous, allogeneic, and xenogeneic bone grafts in 176 patients with maxillofacial diseases. In all, the number of complications did not exceed 5 percent. The allogeneic and xenogeneic grafts were used in the form of small chips of bone. They formed connecting and filler elements for small losses of bones without breaking the continuity of their union. In this group, the number of complications was in the region of 2.5 percent."} {"id": "PMID:157020", "title": "[On the surgical therapy of basaliomata and carcinomata of the facial skin].", "content": "Following surgical therapy, skin carcinomata as well as basaliomata require strict aftercare. Most careful attention should be given especially to dedifferentiated, nonkeratinizing squamous cell carcinomata that usually show a higher rate of relapsing and metastasizing. (2) The relatively high rate of metastasizing of 10 to 20%, which is evident from the literature and could be confirmed by the author for his own patient stock, requires uncompromising removal of the dependent lymphatic region in the form indicated for tumors with the formula T1 N1-2 Mo, T2-3 No Mo, for relapsing carcinomata, and for histologically evident nonkeratinizing squamous cell carcinomata. Only very old age or a poor general condition admit of exceptions to be made.", "contents": "[On the surgical therapy of basaliomata and carcinomata of the facial skin]. Following surgical therapy, skin carcinomata as well as basaliomata require strict aftercare. Most careful attention should be given especially to dedifferentiated, nonkeratinizing squamous cell carcinomata that usually show a higher rate of relapsing and metastasizing. (2) The relatively high rate of metastasizing of 10 to 20%, which is evident from the literature and could be confirmed by the author for his own patient stock, requires uncompromising removal of the dependent lymphatic region in the form indicated for tumors with the formula T1 N1-2 Mo, T2-3 No Mo, for relapsing carcinomata, and for histologically evident nonkeratinizing squamous cell carcinomata. Only very old age or a poor general condition admit of exceptions to be made."} {"id": "PMID:157021", "title": "[On the influence of the time of surgical operation upon dentural development in the case of gnathoplasty, palatoplasty, and uraniscoplasty with simultaneous osteoplasty (author's transl)].", "content": "In patients with cheiloschisis, gnathoschisis, palatoschisis, and uranoschisis, who underwent plastic operations when between four and six years old, maxillary models were biometrically analyzed in the tenth and eleventh years of age. It has been found that the different choice of the time of reparative operation has no influence whatsoever upon maxillary development during childhood. This is of great practical importance especially from a phoniatric and logopedic point of view.", "contents": "[On the influence of the time of surgical operation upon dentural development in the case of gnathoplasty, palatoplasty, and uraniscoplasty with simultaneous osteoplasty (author's transl)]. In patients with cheiloschisis, gnathoschisis, palatoschisis, and uranoschisis, who underwent plastic operations when between four and six years old, maxillary models were biometrically analyzed in the tenth and eleventh years of age. It has been found that the different choice of the time of reparative operation has no influence whatsoever upon maxillary development during childhood. This is of great practical importance especially from a phoniatric and logopedic point of view."} {"id": "PMID:157023", "title": "[Clinical and exfoliative-cytology studies made prior and subsequent to the action of antiovulatory agents upon oral and vaginal mucous membranes (author's transl)].", "content": "Clinical as well as oro- and vaginocytological results obtained from 92 female patients aged 16 to 48, to whom ovulostatic drugs were administered, have been analyzed. Variations in cell composition of the mucosal surface could be detected by exfoliative cytology in the vaginal and oral regions.", "contents": "[Clinical and exfoliative-cytology studies made prior and subsequent to the action of antiovulatory agents upon oral and vaginal mucous membranes (author's transl)]. Clinical as well as oro- and vaginocytological results obtained from 92 female patients aged 16 to 48, to whom ovulostatic drugs were administered, have been analyzed. Variations in cell composition of the mucosal surface could be detected by exfoliative cytology in the vaginal and oral regions."} {"id": "PMID:157024", "title": "[The human dental pulp as viewed through a scanning electron microscope (author's transl)].", "content": "The human dental pulp was examined using a scanning electron microscope. The odontoblasts are pear-shaped and have a fine-grain surface structure. Tomes' process divides into fine branches before entering the predentin. Very few fibroblasts were found. These had stronger cell processes at the two terminal poles. Adhering to their surfaces were fine fibers. Collagenous and nerve fibers could not be accurately identified in the rich fibrillary network of the pulp. Stronger nerve fasciculi were readily observable through longitudinal sulci. Thinner fibers were seen to spread out in branches from some nerve bundles. The capillaries were observed to be surrounded by a sheath of fine fibrils.", "contents": "[The human dental pulp as viewed through a scanning electron microscope (author's transl)]. The human dental pulp was examined using a scanning electron microscope. The odontoblasts are pear-shaped and have a fine-grain surface structure. Tomes' process divides into fine branches before entering the predentin. Very few fibroblasts were found. These had stronger cell processes at the two terminal poles. Adhering to their surfaces were fine fibers. Collagenous and nerve fibers could not be accurately identified in the rich fibrillary network of the pulp. Stronger nerve fasciculi were readily observable through longitudinal sulci. Thinner fibers were seen to spread out in branches from some nerve bundles. The capillaries were observed to be surrounded by a sheath of fine fibrils."} {"id": "PMID:157025", "title": "[Vital microscopic examination of the periodontal blood circulation of incisors in rats (author's transl)].", "content": "This paper describes a method of making microscopic in vivo examinations of the periodontal blood vessels of the lower incisors in rats. On an anesthetized animal, part of the lower jaw is laid open by a U-shaped skin incision and the ligament joining the halves of jaw is cut through. After macrosopic and microscopic preparation, the circulation of blood in the exposed marginal gingiva or in the windowed periodontal space may be observed in vivo by transmitted-light microscopy. The standardized biological model enables the structure and function of the periodontal blood vessels and their normal and disturbed mechanisms of regulation to be examined and compared with conventional histological findings. The functional and morphological parameters are representative of the human periodontium.", "contents": "[Vital microscopic examination of the periodontal blood circulation of incisors in rats (author's transl)]. This paper describes a method of making microscopic in vivo examinations of the periodontal blood vessels of the lower incisors in rats. On an anesthetized animal, part of the lower jaw is laid open by a U-shaped skin incision and the ligament joining the halves of jaw is cut through. After macrosopic and microscopic preparation, the circulation of blood in the exposed marginal gingiva or in the windowed periodontal space may be observed in vivo by transmitted-light microscopy. The standardized biological model enables the structure and function of the periodontal blood vessels and their normal and disturbed mechanisms of regulation to be examined and compared with conventional histological findings. The functional and morphological parameters are representative of the human periodontium."} {"id": "PMID:157026", "title": "[Peak-to-valley height measurement and scanning electron microscopy of cavity walls (author's transl)].", "content": "Using a feeler type of cutting mechanism and a scanning electron microscope, cavity walls were examined subsequent to the preparation thereof with various types of working tools. The combination of these two methods of examination allows results to be obtained which are far better than those achieved with the use of one of these methods alone. The most unfavourable configuration of the cavity wall is obtained using a turbine (diamond). It is especially in the case of inlay preparations that it is necessary for the walls of cavities prepared using a turbine to be retreated by means of a normal-speed type of instrument. Smoothest surfaces are generally obtained with the use of a finisher.", "contents": "[Peak-to-valley height measurement and scanning electron microscopy of cavity walls (author's transl)]. Using a feeler type of cutting mechanism and a scanning electron microscope, cavity walls were examined subsequent to the preparation thereof with various types of working tools. The combination of these two methods of examination allows results to be obtained which are far better than those achieved with the use of one of these methods alone. The most unfavourable configuration of the cavity wall is obtained using a turbine (diamond). It is especially in the case of inlay preparations that it is necessary for the walls of cavities prepared using a turbine to be retreated by means of a normal-speed type of instrument. Smoothest surfaces are generally obtained with the use of a finisher."} {"id": "PMID:157027", "title": "[Biological responses to filling materials with special reference to the composite material evicrol--an experimental study (author's transl)].", "content": "The biological responses to the composite filling material Evicrol were tested by temporarily differentiated implants in rats. Type and degree of the inflammatory reaction as well as the intensity of connective tissue fiber formation were used as criteria for evaluation of the histocompatibility of the subcutaneous implants. As compared to other composite filling materials, Evicrol was found to produce a relatively severe irritation of the tissue. In comparison with silicate cements and also with silicopolyacrylate cement, composite materials including Evicrol were responded to by for less pronounced chronically toxic effects.", "contents": "[Biological responses to filling materials with special reference to the composite material evicrol--an experimental study (author's transl)]. The biological responses to the composite filling material Evicrol were tested by temporarily differentiated implants in rats. Type and degree of the inflammatory reaction as well as the intensity of connective tissue fiber formation were used as criteria for evaluation of the histocompatibility of the subcutaneous implants. As compared to other composite filling materials, Evicrol was found to produce a relatively severe irritation of the tissue. In comparison with silicate cements and also with silicopolyacrylate cement, composite materials including Evicrol were responded to by for less pronounced chronically toxic effects."} {"id": "PMID:157028", "title": "[Experience with evicrol splints after eighteen months of use (author's transl)].", "content": "The authors, after discussing the general importance of the use of splints in parodontological therapy, give a detailed description of the manufacture of composite splints. The experience and results obtained after eighteen months of use of fifteen splints are discussed and compared with data reported in the international literature.", "contents": "[Experience with evicrol splints after eighteen months of use (author's transl)]. The authors, after discussing the general importance of the use of splints in parodontological therapy, give a detailed description of the manufacture of composite splints. The experience and results obtained after eighteen months of use of fifteen splints are discussed and compared with data reported in the international literature."} {"id": "PMID:157029", "title": "[Possibilities to improve the classification of partially edentulous dental arches by the view of morbidity statistics (author's transl)].", "content": "With regard to the planning of treatment capacities in prosthetic dentistry the authors try to find a practicable classification for partially dentulous arches. They make explanations on the classifications, which are known yet. The combination of the EICHNER and KENNEDY classifications as well as an own modification of the KENNEDY system seem to be the best methods for morbidity analysis in this moment.", "contents": "[Possibilities to improve the classification of partially edentulous dental arches by the view of morbidity statistics (author's transl)]. With regard to the planning of treatment capacities in prosthetic dentistry the authors try to find a practicable classification for partially dentulous arches. They make explanations on the classifications, which are known yet. The combination of the EICHNER and KENNEDY classifications as well as an own modification of the KENNEDY system seem to be the best methods for morbidity analysis in this moment."} {"id": "PMID:157030", "title": "[Levels of immunoglobulins and numbers of lymphocytes in the venous blood from the neighbourhood of oral carcinomas Relations to short-time-prognosis (author's transl)].", "content": "Lower levels of immunoglobulins A and G than in a cubital vein were found in the venous blood from the neighbourhood of non-metastatic oral carcinomas. The authors these results interprete as an increased connection of antibodies to the receptors of tumor-cells. It is evident that the receptors are saturated in metastatic carcinomas. Favourable shorttime-prognosis is often connected with an increased number of lymphocytes in blood of tumour- and cubital-vein.", "contents": "[Levels of immunoglobulins and numbers of lymphocytes in the venous blood from the neighbourhood of oral carcinomas Relations to short-time-prognosis (author's transl)]. Lower levels of immunoglobulins A and G than in a cubital vein were found in the venous blood from the neighbourhood of non-metastatic oral carcinomas. The authors these results interprete as an increased connection of antibodies to the receptors of tumor-cells. It is evident that the receptors are saturated in metastatic carcinomas. Favourable shorttime-prognosis is often connected with an increased number of lymphocytes in blood of tumour- and cubital-vein."} {"id": "PMID:157048", "title": "[Variability of the microfloral makeup of the pathological focus in suppurative infection].", "content": "During the period of hospital treatment a change in the composition of would microflora in 145 patients was found to occur, which affected the characteristics of microflora in respect of species, types and strains. This change consisted in the appearance of new (secondary) species, variants and strains and in the disappearance of some original (primary) ones. The populations of staphylococci were found to vary in the level and spectrum of their resistance to antibiotics (resistovars) and in the degree and spectrum of their sensitivity to staphylococcal typing phages (phagovars). Changes in the populations of staphylococci were caused mainly by the cange of S. aureus or by the additional appearance of their new variants which belonged, as a rule, to phage group II, had multiple resistance to antibiotics and corresponded to the phagovars of the hospital flora. The development of hospital variants in open wounds led to an increased general level of resistance of staphylococcal populations to antibiotics.", "contents": "[Variability of the microfloral makeup of the pathological focus in suppurative infection]. During the period of hospital treatment a change in the composition of would microflora in 145 patients was found to occur, which affected the characteristics of microflora in respect of species, types and strains. This change consisted in the appearance of new (secondary) species, variants and strains and in the disappearance of some original (primary) ones. The populations of staphylococci were found to vary in the level and spectrum of their resistance to antibiotics (resistovars) and in the degree and spectrum of their sensitivity to staphylococcal typing phages (phagovars). Changes in the populations of staphylococci were caused mainly by the cange of S. aureus or by the additional appearance of their new variants which belonged, as a rule, to phage group II, had multiple resistance to antibiotics and corresponded to the phagovars of the hospital flora. The development of hospital variants in open wounds led to an increased general level of resistance of staphylococcal populations to antibiotics."} {"id": "PMID:157049", "title": "A simple technique of measuring liver blood flow--intrasplenic injection of 133Xenon.", "content": "Intrasplenic injection of 133Xe was studied as an inert gas clearance technique for measuring liver blood flow in 13 dogs. This was done by comparing technique with intraportal injection of 133Xe (n = 41), and with electromagnetic flowmeter measurements of total liver blood flow. Very good correlation was obtained against the two latter techniques, the correlation coefficients being 0.99 and 0.90 respectively. The comparisons were made over a range of liver blood flow rates from 37 to 297 ml 100 g-1 min-1. The technique is potentially suitable for preoperative measurements, and may be particularly convenient when performed in conjunction with splenoportovenography.", "contents": "A simple technique of measuring liver blood flow--intrasplenic injection of 133Xenon. Intrasplenic injection of 133Xe was studied as an inert gas clearance technique for measuring liver blood flow in 13 dogs. This was done by comparing technique with intraportal injection of 133Xe (n = 41), and with electromagnetic flowmeter measurements of total liver blood flow. Very good correlation was obtained against the two latter techniques, the correlation coefficients being 0.99 and 0.90 respectively. The comparisons were made over a range of liver blood flow rates from 37 to 297 ml 100 g-1 min-1. The technique is potentially suitable for preoperative measurements, and may be particularly convenient when performed in conjunction with splenoportovenography."} {"id": "PMID:157051", "title": "A prospective psychological and cytogenetic study of three girls with mosaic mongolism.", "content": "Three girls with mosaic mongolism (46, XX/47, XX, +21) were followed cytogenetically and psychologically from the time of diagnosis at 8, 17 and 32 months of age, respectively, to the age of 13--15.5 years. All showed muscular hypotonia and hyperflexible joints at the time of diagnosis, but otherwise the physical characteristics of Down's syndrome were weakly expressed. The percentage of trisomic cells in the peripheral blood decresed with time, but were still higher in lymphocytes than in skin fibroblasts at the last investigation. Developmental milestones were delayed in all cases, and the developmental and intelligence quotients were decreased. Mental retardation was only slight in one of the cases (I.G. = 65 at the age of 14 years 8 months). The intelligence quotients showed declining trends with time. Social ability and school results tended to be better than could be expected from the test results.", "contents": "A prospective psychological and cytogenetic study of three girls with mosaic mongolism. Three girls with mosaic mongolism (46, XX/47, XX, +21) were followed cytogenetically and psychologically from the time of diagnosis at 8, 17 and 32 months of age, respectively, to the age of 13--15.5 years. All showed muscular hypotonia and hyperflexible joints at the time of diagnosis, but otherwise the physical characteristics of Down's syndrome were weakly expressed. The percentage of trisomic cells in the peripheral blood decresed with time, but were still higher in lymphocytes than in skin fibroblasts at the last investigation. Developmental milestones were delayed in all cases, and the developmental and intelligence quotients were decreased. Mental retardation was only slight in one of the cases (I.G. = 65 at the age of 14 years 8 months). The intelligence quotients showed declining trends with time. Social ability and school results tended to be better than could be expected from the test results."} {"id": "PMID:157054", "title": "Cation-induced immunosuppression: the effect of lithium or Arthus reactivity, delayed hypersensitivity and antibody production in the rat.", "content": "Arthus reactivity and delayed skin sensitivity to bovine serum albumin (BSA), and anti-BSA antibody production were markedly impaired in female Wistar rats repeatedly injected with lithium chloride.", "contents": "Cation-induced immunosuppression: the effect of lithium or Arthus reactivity, delayed hypersensitivity and antibody production in the rat. Arthus reactivity and delayed skin sensitivity to bovine serum albumin (BSA), and anti-BSA antibody production were markedly impaired in female Wistar rats repeatedly injected with lithium chloride."} {"id": "PMID:157055", "title": "Characterization of reactive and suppressive cells in the mouse embryonic liver by peanut agglutinin (PNA).", "content": "Embryonic liver cells suppressed the MLC response of adult mouse spleen cells and reactivity to mitogens Con A, PHA and LPS. Suppression was exerted by cells agglutinated by PNA (PNA+ cells). Cells reacting to LPS and to DxS were found in the nonagglutinated (PNA-) cell fraction. The PNA+ fraction did not react to DxS nor did it reduce the response of sdult spleen cells to this mitogen.", "contents": "Characterization of reactive and suppressive cells in the mouse embryonic liver by peanut agglutinin (PNA). Embryonic liver cells suppressed the MLC response of adult mouse spleen cells and reactivity to mitogens Con A, PHA and LPS. Suppression was exerted by cells agglutinated by PNA (PNA+ cells). Cells reacting to LPS and to DxS were found in the nonagglutinated (PNA-) cell fraction. The PNA+ fraction did not react to DxS nor did it reduce the response of sdult spleen cells to this mitogen."} {"id": "PMID:157060", "title": "Comparative effects of drugs on four paw oedema models in the rat.", "content": "The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models. We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen, and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs.", "contents": "Comparative effects of drugs on four paw oedema models in the rat. The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models. We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen, and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs."} {"id": "PMID:157062", "title": "A model for establishing occupational therapy and physical therapy services in the public schools.", "content": "One procedure for the establishment of therapists in public schools and on management and administration teams in the State Department of Public Instruction, Division for Exceptional Children is discussed. A significant aspect of the procedure is a model for a working relationship between the Division for Exceptional Children and the Occupational Therapy and Physical Therapy Divisions in the Department of Medical Allied Health Professions in a School of Medicine.", "contents": "A model for establishing occupational therapy and physical therapy services in the public schools. One procedure for the establishment of therapists in public schools and on management and administration teams in the State Department of Public Instruction, Division for Exceptional Children is discussed. A significant aspect of the procedure is a model for a working relationship between the Division for Exceptional Children and the Occupational Therapy and Physical Therapy Divisions in the Department of Medical Allied Health Professions in a School of Medicine."} {"id": "PMID:157063", "title": "Educational mainstreaming of physically handicapped children.", "content": "The therapeutic and educational needs of 31 children who, after attending a private pre-school for the physically handicapped, were mainstrained in public schools are described in this paper. Their adjustment was followed for one to three years. Information was gathered through questionnaires and interviews with parents, children, and classroom teachers on how successful and to what extent the children had been mainstreamed, as well as what physical, academic, and social problems were encountered. Patterns and trends of relative educational abilities and disabilities of children with spina bifida and cerebral palsy are discussed in view of the literature and the problems encountered by this population. Questions that teachers frequently asked of health professionals who are experienced in dealing with the effects of handicapping conditions as well as a procedure for providing this information are also discussed. Successful mainstreaming depends on cooperative work and mutual advocacy among health professionals, parents, and educational personnel.", "contents": "Educational mainstreaming of physically handicapped children. The therapeutic and educational needs of 31 children who, after attending a private pre-school for the physically handicapped, were mainstrained in public schools are described in this paper. Their adjustment was followed for one to three years. Information was gathered through questionnaires and interviews with parents, children, and classroom teachers on how successful and to what extent the children had been mainstreamed, as well as what physical, academic, and social problems were encountered. Patterns and trends of relative educational abilities and disabilities of children with spina bifida and cerebral palsy are discussed in view of the literature and the problems encountered by this population. Questions that teachers frequently asked of health professionals who are experienced in dealing with the effects of handicapping conditions as well as a procedure for providing this information are also discussed. Successful mainstreaming depends on cooperative work and mutual advocacy among health professionals, parents, and educational personnel."} {"id": "PMID:157064", "title": "The school therapist and vocational education.", "content": "Students with disabilities are now placed in regular industrial arts and vocational training programs in secondary schools. Vocational educators agree that teachers need assistance in serving these students with special needs. This paper explores the contributions school occupational therapists can make to vocational education for handicapped students. Recommendations are included for therapists interested in moving into new roles in this field.", "contents": "The school therapist and vocational education. Students with disabilities are now placed in regular industrial arts and vocational training programs in secondary schools. Vocational educators agree that teachers need assistance in serving these students with special needs. This paper explores the contributions school occupational therapists can make to vocational education for handicapped students. Recommendations are included for therapists interested in moving into new roles in this field."} {"id": "PMID:157067", "title": "Back pain: mechanical or inflammatory?", "content": "The majority of patients with a recent onset of back pain that developed rapidly over a few hours have nonspecific spinal disease. The disorder is likely to be self-limited. In contrast, patients presenting with an insidious onset of pain that has lasted for several weeks may have ankylosing spondylitis. Since management differs for the two types of disease, the correct diagnosis is mandatory. The diagnosis of ankylosing spondylitis is confirmed radiologically.", "contents": "Back pain: mechanical or inflammatory? The majority of patients with a recent onset of back pain that developed rapidly over a few hours have nonspecific spinal disease. The disorder is likely to be self-limited. In contrast, patients presenting with an insidious onset of pain that has lasted for several weeks may have ankylosing spondylitis. Since management differs for the two types of disease, the correct diagnosis is mandatory. The diagnosis of ankylosing spondylitis is confirmed radiologically."} {"id": "PMID:157068", "title": "Loss of thick filaments from fast-twitch glucolytic muscle fibers of the pigeon pectoralis after chronic administration of dantrolene sodium.", "content": "Adult pigeons received dantrolene sodium, a skeletal muscle relaxant which blocks the release of calcium during excitation-contraction coupling, for 12 to 16 weeks. The pectoralis muscles of these birds were analyzed for changes occurring in the various fiber types of the muscle. Both histochemistry (ATPase and SDH activity) and electron microscopy (mitochondrial and lipid volume percentages) differentiated two fiber types. The two fiber-types consisted of fast-twitch glycolytic fibers (FG) and fast-twitch oxidative-glycolytic (FOG) fibers. After dantrolene treatment some FG fibers showed little or no ATPase activity. Dantrolene treatment also produced a disappearance of thick filaments in some FG fibers. We infer that the fibers without thick filaments are the ones lacking ATPase activity. The FOG fibers were nearly normal. Since drug-fed birds lose weight, a few birds were starved to determine whether the filament loss was related solely to the bird's loss in weight. No fibers in starved birds showed reduced ATPase activity or loss of thick filaments. In fibers that showed thick filament disappearance, the I-bands remained organized and intact, suggesting that the I-band maintains its integrity without interaction with the thick filaments. Changes in activity patterns may cause loss of thick filaments by inhibiting either their synthesis or assembly.", "contents": "Loss of thick filaments from fast-twitch glucolytic muscle fibers of the pigeon pectoralis after chronic administration of dantrolene sodium. Adult pigeons received dantrolene sodium, a skeletal muscle relaxant which blocks the release of calcium during excitation-contraction coupling, for 12 to 16 weeks. The pectoralis muscles of these birds were analyzed for changes occurring in the various fiber types of the muscle. Both histochemistry (ATPase and SDH activity) and electron microscopy (mitochondrial and lipid volume percentages) differentiated two fiber types. The two fiber-types consisted of fast-twitch glycolytic fibers (FG) and fast-twitch oxidative-glycolytic (FOG) fibers. After dantrolene treatment some FG fibers showed little or no ATPase activity. Dantrolene treatment also produced a disappearance of thick filaments in some FG fibers. We infer that the fibers without thick filaments are the ones lacking ATPase activity. The FOG fibers were nearly normal. Since drug-fed birds lose weight, a few birds were starved to determine whether the filament loss was related solely to the bird's loss in weight. No fibers in starved birds showed reduced ATPase activity or loss of thick filaments. In fibers that showed thick filament disappearance, the I-bands remained organized and intact, suggesting that the I-band maintains its integrity without interaction with the thick filaments. Changes in activity patterns may cause loss of thick filaments by inhibiting either their synthesis or assembly."} {"id": "PMID:157069", "title": "Influences on measured intelligence in Down's syndrome.", "content": "The measured IQ and parental educational level of 57 children with Down's syndrome were compared. The phenomenon of decreasing IW with increasing chronological age in Down's syndrome was considered in the data analysis. There was no trend toward better cognitive performance by children of higher-educated parents. Thirty-one of the children had attended an early, continuous stimulation program. This experience accounted for most of the observed IQ variance.", "contents": "Influences on measured intelligence in Down's syndrome. The measured IQ and parental educational level of 57 children with Down's syndrome were compared. The phenomenon of decreasing IW with increasing chronological age in Down's syndrome was considered in the data analysis. There was no trend toward better cognitive performance by children of higher-educated parents. Thirty-one of the children had attended an early, continuous stimulation program. This experience accounted for most of the observed IQ variance."} {"id": "PMID:157070", "title": "Hypercalcemia associated with neuroblastoma.", "content": "We studied two children with neuroblastoma in whom hypercalcemia developed as the initial manifestation in one and during the course of therapy in the other. Serum parathyroid hormone activity was elevated in the patient in whom the test for it was performed. Mithramycin controlled the hypercalcemia in one patient and tumor resection with radiation therapy and chemotherapy was sufficient for control of this complication in the other.", "contents": "Hypercalcemia associated with neuroblastoma. We studied two children with neuroblastoma in whom hypercalcemia developed as the initial manifestation in one and during the course of therapy in the other. Serum parathyroid hormone activity was elevated in the patient in whom the test for it was performed. Mithramycin controlled the hypercalcemia in one patient and tumor resection with radiation therapy and chemotherapy was sufficient for control of this complication in the other."} {"id": "PMID:157075", "title": "Regulation of hepatic free fatty acid metabolism by glucagon and insulin.", "content": "The roles of glucagon and insulin in the direct short-term regulation of hepatic free fatty acid (FFA) metabolism were studied in hepatocytes isolated from fed, fasted, and streptozotocin-induced diabetic rats. In fed animals, the principal metabolic product of palmitate metabolism was triglyceride, whereas ketones were the major product in fasted and diabetic animals. Glucagon at physiological concentrations increased ketogenesis and decreased triglyceride synthesis from palmitate in hepatocytes from fed rats at FFA concentrations 1.0 mM or less. Insulin had no effect on FFA metabolism when present as the sole hormone, but could antagonize the actions of submaximal concentrations of glucagon. The metabolism of palmitate in fasted or diabetic hepatocytes was unaffected by either hormone. Ketogenesis from octanoate was also unaffected by hormone addition in all cell types. These data are consistent with a locus of hormonal regulation at a step prior to beta-oxidation of fatty acid. Glucagon and insulin may modulate FFA metabolism by both intrahepatic and extrahepatic mechanisms.", "contents": "Regulation of hepatic free fatty acid metabolism by glucagon and insulin. The roles of glucagon and insulin in the direct short-term regulation of hepatic free fatty acid (FFA) metabolism were studied in hepatocytes isolated from fed, fasted, and streptozotocin-induced diabetic rats. In fed animals, the principal metabolic product of palmitate metabolism was triglyceride, whereas ketones were the major product in fasted and diabetic animals. Glucagon at physiological concentrations increased ketogenesis and decreased triglyceride synthesis from palmitate in hepatocytes from fed rats at FFA concentrations 1.0 mM or less. Insulin had no effect on FFA metabolism when present as the sole hormone, but could antagonize the actions of submaximal concentrations of glucagon. The metabolism of palmitate in fasted or diabetic hepatocytes was unaffected by either hormone. Ketogenesis from octanoate was also unaffected by hormone addition in all cell types. These data are consistent with a locus of hormonal regulation at a step prior to beta-oxidation of fatty acid. Glucagon and insulin may modulate FFA metabolism by both intrahepatic and extrahepatic mechanisms."} {"id": "PMID:157076", "title": "Efficacy of metronidazole in dracunculiasis. A clinical trial.", "content": "In a clinical trial of metronidazole for dracunculiasis (75 cases), the drug was effective in giving symptomatic relief but had no preventive or vermicidal action. It was well tolerated. No difference was observed in the results of two dose schedules (200 mg or 400 mg three times daily for 10 days).", "contents": "Efficacy of metronidazole in dracunculiasis. A clinical trial. In a clinical trial of metronidazole for dracunculiasis (75 cases), the drug was effective in giving symptomatic relief but had no preventive or vermicidal action. It was well tolerated. No difference was observed in the results of two dose schedules (200 mg or 400 mg three times daily for 10 days)."} {"id": "PMID:157077", "title": "Axillofemoral bypass: a critical reappraisal of its role in the management of aortoiliac occlusive disease.", "content": "Two hundred twenty-four consecutive patients (361 graft limbs) who underwent bypass grafting with the USCI Sauvage filamentous velour Dacron arterial prosthesis for aortoiliac occlusive disease over the 9 year period 1970 to 1979 are reviewed. Eighty-four axillofemoral (23 percent of patients), 210 aortofemoral (47 percent of patients), and 67 femorofemoral grafts (30 percent of patients) had cumulative patency rates of 72.1, 91.1, and 86.4 percent, respectively. Experimental and clinical factors influencing the patency of axillofemoral grafts are discussed, and the concept of an improved porous Dacron prosthesis specific for the axillofemoral site is presented.", "contents": "Axillofemoral bypass: a critical reappraisal of its role in the management of aortoiliac occlusive disease. Two hundred twenty-four consecutive patients (361 graft limbs) who underwent bypass grafting with the USCI Sauvage filamentous velour Dacron arterial prosthesis for aortoiliac occlusive disease over the 9 year period 1970 to 1979 are reviewed. Eighty-four axillofemoral (23 percent of patients), 210 aortofemoral (47 percent of patients), and 67 femorofemoral grafts (30 percent of patients) had cumulative patency rates of 72.1, 91.1, and 86.4 percent, respectively. Experimental and clinical factors influencing the patency of axillofemoral grafts are discussed, and the concept of an improved porous Dacron prosthesis specific for the axillofemoral site is presented."} {"id": "PMID:157078", "title": "Flow wave form analysis in vascular surgery.", "content": "An analysis of 82 limbs subjected to femoropopliteal bypass grafting demonstrated that electromagnetic flow wave forms of the reconstructed vessel are a reliable indicator in predicting the outcome of surgery. On the basis of this knowledge, postoperative follow-up study of patients who had undergone reconstructive surgery was carried out. Early occult occlusive lesions were detected in 5 of 56 limbs examined, and 3 of these patients underwent successful reoperation with satisfactory restoration of blood flow. Follow-up study using flow wave form analysis is a useful method of detecting occult changes in arteries and leads to early treatment.", "contents": "Flow wave form analysis in vascular surgery. An analysis of 82 limbs subjected to femoropopliteal bypass grafting demonstrated that electromagnetic flow wave forms of the reconstructed vessel are a reliable indicator in predicting the outcome of surgery. On the basis of this knowledge, postoperative follow-up study of patients who had undergone reconstructive surgery was carried out. Early occult occlusive lesions were detected in 5 of 56 limbs examined, and 3 of these patients underwent successful reoperation with satisfactory restoration of blood flow. Follow-up study using flow wave form analysis is a useful method of detecting occult changes in arteries and leads to early treatment."} {"id": "PMID:157090", "title": "Doppler ultrasound in the evaluation of the peripheral arterial circulation.", "content": "This review summarizes the principle, advantages, and limitations of Doppler ultrasound flowmeters, and discusses the possibilities of applying these systems in evaluating the functional state of the peripheral arterial circulation. This discussion is not limited to the assessment of blood flow velocity and poststenotic arterial pressure with Doppler flowmeters, but includes among other things the recordings of flow patterns, the determination of the transit time of velocity wave forms, and the imaging of the arterial circulation.", "contents": "Doppler ultrasound in the evaluation of the peripheral arterial circulation. This review summarizes the principle, advantages, and limitations of Doppler ultrasound flowmeters, and discusses the possibilities of applying these systems in evaluating the functional state of the peripheral arterial circulation. This discussion is not limited to the assessment of blood flow velocity and poststenotic arterial pressure with Doppler flowmeters, but includes among other things the recordings of flow patterns, the determination of the transit time of velocity wave forms, and the imaging of the arterial circulation."} {"id": "PMID:157091", "title": "[Multiple hepatic cysts in rat rendered diabetic by streptozotocin and treated by islets of Langerhans grafts: the role of streptozotocin].", "content": "This study is based on the investigation by light and electron microscopy of hepatic biopsies from 14 rats rendered diabetic by streptozotocin and treated by portal embolization of islets of Langerhans. Macroscopically, voluminous projecting cysts were observed, sometimes occupying a whole lobe. By light microscopy, the cysts were lined with canalicular-type epithelium. Ultrastructural studies confirmed the canalicular nature of these cells and cilia were frequently observed. The presence of identical cysts in rats rendered diabetic by streptozotocin but not treated by embolization proves that this product is the agent responsible for the induction of this adenomatosis.", "contents": "[Multiple hepatic cysts in rat rendered diabetic by streptozotocin and treated by islets of Langerhans grafts: the role of streptozotocin]. This study is based on the investigation by light and electron microscopy of hepatic biopsies from 14 rats rendered diabetic by streptozotocin and treated by portal embolization of islets of Langerhans. Macroscopically, voluminous projecting cysts were observed, sometimes occupying a whole lobe. By light microscopy, the cysts were lined with canalicular-type epithelium. Ultrastructural studies confirmed the canalicular nature of these cells and cilia were frequently observed. The presence of identical cysts in rats rendered diabetic by streptozotocin but not treated by embolization proves that this product is the agent responsible for the induction of this adenomatosis."} {"id": "PMID:157092", "title": "Histochemical localization of adenosine triphosphatase activity in bovine ruminal epithelium.", "content": "A fine-structural histochemical technique was used to localize magnesium-dependent adenosine triphosphatase (Mg-ATPase) activity in ruminal mucosa. Precipitate appeared on the cytoplasmic surface of the plasmalemma in cells of the upper stratum spinosum, the stratum granulosum, and the deepest layer of the stratum corneum. This ATPase activity was sensitive to glutaraldehyde fixation and possibly to ouabain, but was unaffected by sodium and potassium. The preponderance of Mg-ATPase activity in bovine ruminal epithelium may make it impossible to detect sodium-potassium-activated adenosine triphosphatase ((Na + K)-ATPase) activity histochemically. A Mg-ATPase activity also occurred in mitochondria of the stratum spinosum and stratum granulosum. None of the ruminal sections hydrolyzed adenosine diphosphate, inosine triphosphate, or beta-glycerophosphate when these compounds were used as substitute substrates for adenosine triphosphate. When adenosine-5'-monophosphate was the available substrate, a reaction product appeared in the same layers as Mg-ATPase activity, but the reaction product was confined to the intercellular space.", "contents": "Histochemical localization of adenosine triphosphatase activity in bovine ruminal epithelium. A fine-structural histochemical technique was used to localize magnesium-dependent adenosine triphosphatase (Mg-ATPase) activity in ruminal mucosa. Precipitate appeared on the cytoplasmic surface of the plasmalemma in cells of the upper stratum spinosum, the stratum granulosum, and the deepest layer of the stratum corneum. This ATPase activity was sensitive to glutaraldehyde fixation and possibly to ouabain, but was unaffected by sodium and potassium. The preponderance of Mg-ATPase activity in bovine ruminal epithelium may make it impossible to detect sodium-potassium-activated adenosine triphosphatase ((Na + K)-ATPase) activity histochemically. A Mg-ATPase activity also occurred in mitochondria of the stratum spinosum and stratum granulosum. None of the ruminal sections hydrolyzed adenosine diphosphate, inosine triphosphate, or beta-glycerophosphate when these compounds were used as substitute substrates for adenosine triphosphate. When adenosine-5'-monophosphate was the available substrate, a reaction product appeared in the same layers as Mg-ATPase activity, but the reaction product was confined to the intercellular space."} {"id": "PMID:157093", "title": "Immune complex disease in guinea pig lungs: elicitation with pigeon serum.", "content": "Immune complex- and T cell-mediated reactions to organic antigens appear to contribute to the pathogenesis of hypersensitivity pneumonitis in humans. Because pigeon serum is one of the reagents used by clinicians to diagnose this disease, we assessed its potential to elicit immune complex-mediated pulmonary inflammation in guinea pigs. Animals were immunized with different concentrations of pigeon serum protein emulsified in complete Freund's adjuvant, and serums were collected at 4-day intervals after the booster injection. The largest amounts of tissue-fixing (IgG1) and complement-fixing (IgG2) antibodies to pigeon serum were detected in guinea pigs immunized with 1.0 mg of pigeon serum protein 20 to 24 days after the secondary immunization. Therefore, the responses of these animals and of recipients of serum from these animals to aerosol challenge with either homologous (pigeon serum) or heterologous (bovine gamma globulin) immunogen was investigated. Actively and passively immunized guinea pigs developed pulmonary inflammation only after exposure to aerosolized pigeon serum. However, lesions were not observed in the lungs of complement-deficient recipients of immune serum that had inhaled homologous immunogen. These observations suggest that such pigeon serum-elicited pulmonary inflammation in guinea pigs is a manifestation of a complement-dependent, humoral-immune mechanism of pathogenesis and thus is consistent with an immune complex disease.", "contents": "Immune complex disease in guinea pig lungs: elicitation with pigeon serum. Immune complex- and T cell-mediated reactions to organic antigens appear to contribute to the pathogenesis of hypersensitivity pneumonitis in humans. Because pigeon serum is one of the reagents used by clinicians to diagnose this disease, we assessed its potential to elicit immune complex-mediated pulmonary inflammation in guinea pigs. Animals were immunized with different concentrations of pigeon serum protein emulsified in complete Freund's adjuvant, and serums were collected at 4-day intervals after the booster injection. The largest amounts of tissue-fixing (IgG1) and complement-fixing (IgG2) antibodies to pigeon serum were detected in guinea pigs immunized with 1.0 mg of pigeon serum protein 20 to 24 days after the secondary immunization. Therefore, the responses of these animals and of recipients of serum from these animals to aerosol challenge with either homologous (pigeon serum) or heterologous (bovine gamma globulin) immunogen was investigated. Actively and passively immunized guinea pigs developed pulmonary inflammation only after exposure to aerosolized pigeon serum. However, lesions were not observed in the lungs of complement-deficient recipients of immune serum that had inhaled homologous immunogen. These observations suggest that such pigeon serum-elicited pulmonary inflammation in guinea pigs is a manifestation of a complement-dependent, humoral-immune mechanism of pathogenesis and thus is consistent with an immune complex disease."} {"id": "PMID:157089", "title": "Kinetics of the enzymatic pattern in the testis. I. Stage dependence of enzymatic activity and its relation to cellular interactions in the testis of the Wistar rat.", "content": "The \"morphology\" of the enzymatic activities of thiamine pyrophosphatase (TPPase), acid phosphatases (ACPases), adenosine triphosphatase (ATPase) and steroid-3 beta-ol dehydrogenase (St-3 beta-ol DH) has been described using as a basis the classification of the seminiferous epithelium of the rat into 14 stages as proposed by Leblond and Clermont (1952a, b). It was demonstrated (Figs. 1, 2) that 1. the kinetics of the enzymatic pattern is correlated with the developmental stages during spermatocyto- and spermiogenesis, and that therefore the chemocytostructure, especially of the germ cells, shows characteristic changes. 2. the enzymatic pattern yields information on the chemohistostructure of the testis, and thus indicates interactions between the germ cells and the coordinated somatic cells. This is valid especially for the behaviour of the \"marker enzymes\" TPPase and ACPases. Initially the activity of both enzymes is distributed in the cytoplasm: TPPase appears in stage VII in the preleptotene spermatocytes, and ACPases appear in stage VII in the pachytene spermatocytes. In the following stages the activity of TPPase and ACPases increases and becomes more and more concentrated, i.e. from stage IX to XIV and thereafter from stage I to XIII in the case of TPPase, and from stage I to XIII in the case of ACPases. Finally the enzymatic activity of both TPPase and ACPases is arranged in spherical bodies near the nucleus of the spermatocytes. Thus the late pachytene and diplotene spermatocytes, as well as the spermatocytes in diakinesis, are characterized by deeply stained spherical dots covering the region of the Golgi apparatus. Both enzymes disappear during the maturation divisions--parts of the cytoplasm of the II-spermatocytes during interphase react weakly positive--, reappear in the Golgi region of the newly formed spermatids in stage I, remain there up to stage V in the case of ACPases, and up to stage VII in the case of TPPase. From stages VIII to XIV TPPase is weakly positive in the Golgi apparatus of the elongating spermatids, moving within the cytoplasm from the head region towards the tail. Finally they appear in the cytoplasm of the Sertoli cells: (1) ACPases appear in the borderline region between the Sertoli cells and the elongated spermatids in stages XII to XIV (2) TPPase first appears in the basal region of the Sertoli cells in stages XI to XIV, and becomes positive in the subsequent stages I to IV as \"streamer like\" bands from the basement membrane up to the heads of the elongated spermatids. Both enzymes disappear gradually during stages I to III and IV to V respectively. Stage dependence of ATPase can be observed in the apical region of the Sertoli cells around the heads and the middle pieces of the elongated spermatids. ATPase appears for the first time in stages IX to X, and becomes increasingly more and more concentrated and condensed up to the point when the newly formed spermatozoa are released in stage VIII...", "contents": "Kinetics of the enzymatic pattern in the testis. I. Stage dependence of enzymatic activity and its relation to cellular interactions in the testis of the Wistar rat. The \"morphology\" of the enzymatic activities of thiamine pyrophosphatase (TPPase), acid phosphatases (ACPases), adenosine triphosphatase (ATPase) and steroid-3 beta-ol dehydrogenase (St-3 beta-ol DH) has been described using as a basis the classification of the seminiferous epithelium of the rat into 14 stages as proposed by Leblond and Clermont (1952a, b). It was demonstrated (Figs. 1, 2) that 1. the kinetics of the enzymatic pattern is correlated with the developmental stages during spermatocyto- and spermiogenesis, and that therefore the chemocytostructure, especially of the germ cells, shows characteristic changes. 2. the enzymatic pattern yields information on the chemohistostructure of the testis, and thus indicates interactions between the germ cells and the coordinated somatic cells. This is valid especially for the behaviour of the \"marker enzymes\" TPPase and ACPases. Initially the activity of both enzymes is distributed in the cytoplasm: TPPase appears in stage VII in the preleptotene spermatocytes, and ACPases appear in stage VII in the pachytene spermatocytes. In the following stages the activity of TPPase and ACPases increases and becomes more and more concentrated, i.e. from stage IX to XIV and thereafter from stage I to XIII in the case of TPPase, and from stage I to XIII in the case of ACPases. Finally the enzymatic activity of both TPPase and ACPases is arranged in spherical bodies near the nucleus of the spermatocytes. Thus the late pachytene and diplotene spermatocytes, as well as the spermatocytes in diakinesis, are characterized by deeply stained spherical dots covering the region of the Golgi apparatus. Both enzymes disappear during the maturation divisions--parts of the cytoplasm of the II-spermatocytes during interphase react weakly positive--, reappear in the Golgi region of the newly formed spermatids in stage I, remain there up to stage V in the case of ACPases, and up to stage VII in the case of TPPase. From stages VIII to XIV TPPase is weakly positive in the Golgi apparatus of the elongating spermatids, moving within the cytoplasm from the head region towards the tail. Finally they appear in the cytoplasm of the Sertoli cells: (1) ACPases appear in the borderline region between the Sertoli cells and the elongated spermatids in stages XII to XIV (2) TPPase first appears in the basal region of the Sertoli cells in stages XI to XIV, and becomes positive in the subsequent stages I to IV as \"streamer like\" bands from the basement membrane up to the heads of the elongated spermatids. Both enzymes disappear gradually during stages I to III and IV to V respectively. Stage dependence of ATPase can be observed in the apical region of the Sertoli cells around the heads and the middle pieces of the elongated spermatids. ATPase appears for the first time in stages IX to X, and becomes increasingly more and more concentrated and condensed up to the point when the newly formed spermatozoa are released in stage VIII..."} {"id": "PMID:157094", "title": "Clinical indicators of left main coronary artery disease in unstable angina.", "content": "Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (greater than or equal to 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography.", "contents": "Clinical indicators of left main coronary artery disease in unstable angina. Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (greater than or equal to 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography."} {"id": "PMID:157095", "title": "Autoantibodies and the spectrum of Sj\u00f6gren's syndrome.", "content": "In studies reported recently, the sera of patients with Sj\u00f6gren's syndrome were found to contain precipitating antibodies to nuclear antigens that can be identified by immunodiffusion analysis. These precipitating autoantibodies have been termed SS-A and SS-B antibodies. We show that identification of these autoantibodies helped in establishing the diagnosis of Sj\u00f6gren's syndrome in 12 of 30 patients in whom the diagnosis had not been considered at the time of the physician's initial examination. The reasons for this were related to lack of spontaneous complaints of keratoconjunctivitis sicca and xerostomia and prominence of symptoms associated with arthritis, myalgia, pulmonary fibrosis, and cardiac disease. This study re-emphasizes the importance of multisystem disease in Sj\u00f6gren's syndrome and shows that specific serologic assays for autoantibodies aided in diagnosis.", "contents": "Autoantibodies and the spectrum of Sj\u00f6gren's syndrome. In studies reported recently, the sera of patients with Sj\u00f6gren's syndrome were found to contain precipitating antibodies to nuclear antigens that can be identified by immunodiffusion analysis. These precipitating autoantibodies have been termed SS-A and SS-B antibodies. We show that identification of these autoantibodies helped in establishing the diagnosis of Sj\u00f6gren's syndrome in 12 of 30 patients in whom the diagnosis had not been considered at the time of the physician's initial examination. The reasons for this were related to lack of spontaneous complaints of keratoconjunctivitis sicca and xerostomia and prominence of symptoms associated with arthritis, myalgia, pulmonary fibrosis, and cardiac disease. This study re-emphasizes the importance of multisystem disease in Sj\u00f6gren's syndrome and shows that specific serologic assays for autoantibodies aided in diagnosis."} {"id": "PMID:157096", "title": "The chronicity of symptoms and disability in Reiter's syndrome. An analysis of 131 consecutive patients.", "content": "To assess the natural history of Reiter's disease, we evaluated 131 consecutive patients at a university clinic or at a community center. One hundred twenty-two patients (93%) were available for follow-up at a mean of 5.6 years. The results showed that there were no major differences between patients at the two centers; at follow-up, 101 (83%) had some disease activity, 27 (22%) had annoying symptoms, 42 (34%) had sustained disease activity, 19 (16%) had had to change jobs, and 13 (11%) were unemployable; there were no major differences between the 19 (15%) females and 112 (85%) males or between the HLA-B27-positive (83%) and -negative (17%) patients, except for increased prevalence of sacroilitis and chronic uveitis in HLA-B27-positive patients; and, at entry, only increased heel disease differentiated those destined to have a poor prognosis. Most patients with Reiter's syndrome have persisting symptoms that can lead to chronic disability.", "contents": "The chronicity of symptoms and disability in Reiter's syndrome. An analysis of 131 consecutive patients. To assess the natural history of Reiter's disease, we evaluated 131 consecutive patients at a university clinic or at a community center. One hundred twenty-two patients (93%) were available for follow-up at a mean of 5.6 years. The results showed that there were no major differences between patients at the two centers; at follow-up, 101 (83%) had some disease activity, 27 (22%) had annoying symptoms, 42 (34%) had sustained disease activity, 19 (16%) had had to change jobs, and 13 (11%) were unemployable; there were no major differences between the 19 (15%) females and 112 (85%) males or between the HLA-B27-positive (83%) and -negative (17%) patients, except for increased prevalence of sacroilitis and chronic uveitis in HLA-B27-positive patients; and, at entry, only increased heel disease differentiated those destined to have a poor prognosis. Most patients with Reiter's syndrome have persisting symptoms that can lead to chronic disability."} {"id": "PMID:157101", "title": "Preliminary observations on the synthesis of glycosaminoglycans in the sea urchin embryo.", "content": "A method based on the degradation by enzymes and nitrous acid of isotopically labelled glycosaminoglycans has been employed to study the synthesis of these compounds in normal, animalized and vegetalized sea urchin embryos. According to standard criteria, these organisms synthesize dermatan sulfate, heparan sulfate, hyaluronate and keratan sulfate. The hyaluronate seems to be slightly sulfated, it may thus be mucoitin sulfate. The preliminary results obtained suggest a conspicuous difference between animalized and vegetalized embryos: the synthesis of dermatan sulfate is suppressed in the former, while proceeding normally in the latter. The synthesis of heparan sulfate is not affected by our experimental conditions, but the isotope incorporation in hyaluronate and in keratan sulfate is decreased, more in the vegetalized than in the animalized embryos.", "contents": "Preliminary observations on the synthesis of glycosaminoglycans in the sea urchin embryo. A method based on the degradation by enzymes and nitrous acid of isotopically labelled glycosaminoglycans has been employed to study the synthesis of these compounds in normal, animalized and vegetalized sea urchin embryos. According to standard criteria, these organisms synthesize dermatan sulfate, heparan sulfate, hyaluronate and keratan sulfate. The hyaluronate seems to be slightly sulfated, it may thus be mucoitin sulfate. The preliminary results obtained suggest a conspicuous difference between animalized and vegetalized embryos: the synthesis of dermatan sulfate is suppressed in the former, while proceeding normally in the latter. The synthesis of heparan sulfate is not affected by our experimental conditions, but the isotope incorporation in hyaluronate and in keratan sulfate is decreased, more in the vegetalized than in the animalized embryos."} {"id": "PMID:157103", "title": "Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population.", "content": "A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population.", "contents": "Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population. A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population."} {"id": "PMID:157100", "title": "Idiotype-related cellular events during the anamnestic immune response to Salmonella typhi in rabbits.", "content": "Himalayan rabbits of a closed colony were immunized with injections of heat-killed Salmonella typhi and antiidiotypic antibodies against the induced anti- S. typhi antibodies were produced in rabbits of the same colony as well as in random-bred rabbits. Rabbits of the closed colony showed no proliferative response in a mixed lymphocyte culture of peripheral blood. Antiidiotypic sera from Himalayan rabbits recognized the idiotype in the corresponding immunizing sera alone, while one of sera from random-bred rabbits showed a cross-reaction with 8 out of 10 anti-S. typhi sera of Himalayan rabbits but not with any of 10 anti-S. typhi sera of unrelated random-bred rabbits. The cross-reactivity of the antiserum remained intact after absorption with unrelated immune precipitates. With this antiidiotypic serum the immunizing serum formed a bimodial arc at beta-gamma mobility and all other anti-S. typhi sera containing the cross-reactive idiotype a single arc at beta mobility. Solubilized immune precipitates of cross-reactive idiotype-anti-idiotype reaction could bind radiolabelled lipopolysaccharide (LPS) from S. typhi, but this anti-LPS activity was not revealed in an isoelectric focusing analysis. Gel analysis showed that the cross-reactive idiotype was located mainly in the macroglobulin fractions. The idiotype in the serum of the immunizing rabbits diminished and then was undetectable following the 2nd and the 3rd immunizations. When 3H-TdR uptake was examined in a mixed cell culture of peripheral blood from immunizing and antiidiotypic rabbits, there was a fluctuation in the proliferative response with two peaks occurring at a 4-week interval. An analysis of such a proliferative response was carried out by separating leukocytes and plasma from blood of the immunizing and the antiidiotypic rabbits. Mixed culture of cells alone did not produce a proliferative response, while culture of cells from the immunizing rabbit together with antiidiotypic plasma resulted in a potent reaction, irrespective of the presence of plasma from the immunizing rabbit. Presence of cells from the antiidiotypic rabbit in the culture inhibited this proliferative response. A fluctuation in the proliferative response to antiidiotypic serum was also observed with peripheral blood leukocytes (PBL) from rabbits producing the cross-reactive idiotype, while the antiidiotypic serum did not stimulate cells from rabbits which had been similarly immunized with S. typhi but did not produce the idiotype. PBL from the immunizing rabbit where the idiotype production ceased following the tertiary immunization were found to suppress definitely the proliferative response induced by the cross-reactive idiotype-anti-idiotype reaction. The suppressive activity was lost in PBL from the same rabbit after a cortisone treatment and the following antigenic stimulation of the animal led to reappearance in the serum of the idiotype. These results support the immune regulatory model which involves idiotype-anti-idiotype interactions.", "contents": "Idiotype-related cellular events during the anamnestic immune response to Salmonella typhi in rabbits. Himalayan rabbits of a closed colony were immunized with injections of heat-killed Salmonella typhi and antiidiotypic antibodies against the induced anti- S. typhi antibodies were produced in rabbits of the same colony as well as in random-bred rabbits. Rabbits of the closed colony showed no proliferative response in a mixed lymphocyte culture of peripheral blood. Antiidiotypic sera from Himalayan rabbits recognized the idiotype in the corresponding immunizing sera alone, while one of sera from random-bred rabbits showed a cross-reaction with 8 out of 10 anti-S. typhi sera of Himalayan rabbits but not with any of 10 anti-S. typhi sera of unrelated random-bred rabbits. The cross-reactivity of the antiserum remained intact after absorption with unrelated immune precipitates. With this antiidiotypic serum the immunizing serum formed a bimodial arc at beta-gamma mobility and all other anti-S. typhi sera containing the cross-reactive idiotype a single arc at beta mobility. Solubilized immune precipitates of cross-reactive idiotype-anti-idiotype reaction could bind radiolabelled lipopolysaccharide (LPS) from S. typhi, but this anti-LPS activity was not revealed in an isoelectric focusing analysis. Gel analysis showed that the cross-reactive idiotype was located mainly in the macroglobulin fractions. The idiotype in the serum of the immunizing rabbits diminished and then was undetectable following the 2nd and the 3rd immunizations. When 3H-TdR uptake was examined in a mixed cell culture of peripheral blood from immunizing and antiidiotypic rabbits, there was a fluctuation in the proliferative response with two peaks occurring at a 4-week interval. An analysis of such a proliferative response was carried out by separating leukocytes and plasma from blood of the immunizing and the antiidiotypic rabbits. Mixed culture of cells alone did not produce a proliferative response, while culture of cells from the immunizing rabbit together with antiidiotypic plasma resulted in a potent reaction, irrespective of the presence of plasma from the immunizing rabbit. Presence of cells from the antiidiotypic rabbit in the culture inhibited this proliferative response. A fluctuation in the proliferative response to antiidiotypic serum was also observed with peripheral blood leukocytes (PBL) from rabbits producing the cross-reactive idiotype, while the antiidiotypic serum did not stimulate cells from rabbits which had been similarly immunized with S. typhi but did not produce the idiotype. PBL from the immunizing rabbit where the idiotype production ceased following the tertiary immunization were found to suppress definitely the proliferative response induced by the cross-reactive idiotype-anti-idiotype reaction. The suppressive activity was lost in PBL from the same rabbit after a cortisone treatment and the following antigenic stimulation of the animal led to reappearance in the serum of the idiotype. These results support the immune regulatory model which involves idiotype-anti-idiotype interactions."} {"id": "PMID:157104", "title": "Tinea versicolor with regard to seborrheic dermatitis. An epidemiological investigation.", "content": "This is a retrospective study of 232 patients, and a prospective survey of 48 patients, regarding susceptibility factors in tinea versicolor, particularly in association with seborrheic dermatitis. In both surveys, a higher (10.4%) than expected (3.8%) percentage of association with seborrheic dermatitis was found.", "contents": "Tinea versicolor with regard to seborrheic dermatitis. An epidemiological investigation. This is a retrospective study of 232 patients, and a prospective survey of 48 patients, regarding susceptibility factors in tinea versicolor, particularly in association with seborrheic dermatitis. In both surveys, a higher (10.4%) than expected (3.8%) percentage of association with seborrheic dermatitis was found."} {"id": "PMID:157105", "title": "Granular layer induction following the topical application of proliferating agents.", "content": "Evidence is provided for a possible dermal influence on the epidermis. Topical vitamin A stimulates a number of dermal cells with different enzyme reactions, and these invade the epidermis at about the time a granular layer is induced in mouse tail scale epidermis. N-hexadecane also induced a granular layer formation in the tail scale epidermis but the application of this agent only results in the invasion of the epidermis by non-specific esterase cells. These non-specific esterase cells are present in the follicular zone where a granular layer is usually present. It appears that dendritic cells may be responsible for the formation of a granular layer and that these cells in some way influence the keratinocytes to discharge their lyosomal enzymes and thus form a granular layer. It appears unlikely that the dendritic cells actually contribute their own acid hydrolases to the cell cytolysis necessary for the production of granular layer.", "contents": "Granular layer induction following the topical application of proliferating agents. Evidence is provided for a possible dermal influence on the epidermis. Topical vitamin A stimulates a number of dermal cells with different enzyme reactions, and these invade the epidermis at about the time a granular layer is induced in mouse tail scale epidermis. N-hexadecane also induced a granular layer formation in the tail scale epidermis but the application of this agent only results in the invasion of the epidermis by non-specific esterase cells. These non-specific esterase cells are present in the follicular zone where a granular layer is usually present. It appears that dendritic cells may be responsible for the formation of a granular layer and that these cells in some way influence the keratinocytes to discharge their lyosomal enzymes and thus form a granular layer. It appears unlikely that the dendritic cells actually contribute their own acid hydrolases to the cell cytolysis necessary for the production of granular layer."} {"id": "PMID:157107", "title": "The feasibility of replacing antibiotics by quaternary ammonium compounds in topical antimicrobial acne therapy.", "content": "Determinations of the minimum inhibitory concentrations for various antimicrobial surfactants with reference to the bacteria P. acnes, P. granulosum, and St. epidermidis are reported. The results show that quaternary ammonium compounds can display minimum inhibitory concentrations corresponding to those of relevant antibiotics. With the especially effective substance fractionated dimethylcocobenzalkoniumchloride )ARQUAD DMMCD-B), it could be further shown that with in vivo application in 70% isopropanol or in an ethanol-containing film mask ointment suppression can be obtained of P. acnes, all propionibacteria added, and all pilosebaceous duct bacteria which can be cultured under anaerobic conditions. The studies may point out a way of replacing antibiotics in the antimicrobial therapy of acne by quaternary ammonium compounds.", "contents": "The feasibility of replacing antibiotics by quaternary ammonium compounds in topical antimicrobial acne therapy. Determinations of the minimum inhibitory concentrations for various antimicrobial surfactants with reference to the bacteria P. acnes, P. granulosum, and St. epidermidis are reported. The results show that quaternary ammonium compounds can display minimum inhibitory concentrations corresponding to those of relevant antibiotics. With the especially effective substance fractionated dimethylcocobenzalkoniumchloride )ARQUAD DMMCD-B), it could be further shown that with in vivo application in 70% isopropanol or in an ethanol-containing film mask ointment suppression can be obtained of P. acnes, all propionibacteria added, and all pilosebaceous duct bacteria which can be cultured under anaerobic conditions. The studies may point out a way of replacing antibiotics in the antimicrobial therapy of acne by quaternary ammonium compounds."} {"id": "PMID:157108", "title": "Five year study of tissue reaction to synthetic sutures.", "content": "Sutures were implanted in the abdominal wall muscles of rabbits and specimens recovered at intervals from six month to five years. Tissue reaction around Nylon and Dacron was minimal. The reaction of Teflon coated Dacron was increased because of shedding of the Teflon. The polypropylene sutures showed fragmentation in 4% of the sutures examined and the perisutural formation of bone, cartilage or both in 2.6%.", "contents": "Five year study of tissue reaction to synthetic sutures. Sutures were implanted in the abdominal wall muscles of rabbits and specimens recovered at intervals from six month to five years. Tissue reaction around Nylon and Dacron was minimal. The reaction of Teflon coated Dacron was increased because of shedding of the Teflon. The polypropylene sutures showed fragmentation in 4% of the sutures examined and the perisutural formation of bone, cartilage or both in 2.6%."} {"id": "PMID:157110", "title": "Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.", "content": "We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed.", "contents": "Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis. We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed."} {"id": "PMID:157112", "title": "Race and sex as variables affecting reactions to disability.", "content": "Several aspects of reaction to disability were compared across samples of rehabilitation patients which differed in race and sex. Subjects included 28 black men, 14 white men, 19 black women, and 19 white women who had a range of different disabilities and who were patients at a large public hospital and a small rehabilitation center in a southeastern metropolis. Losses attributed to disability were found to vary for men and women, except that inability to work was missed most by all subjects. Only black men emphasized themselves, their jobs, and other persons as reasons for their disability. All subjects were most likely to cite mystical causes for their disability and to believe that mystical sources would most help them to improve.", "contents": "Race and sex as variables affecting reactions to disability. Several aspects of reaction to disability were compared across samples of rehabilitation patients which differed in race and sex. Subjects included 28 black men, 14 white men, 19 black women, and 19 white women who had a range of different disabilities and who were patients at a large public hospital and a small rehabilitation center in a southeastern metropolis. Losses attributed to disability were found to vary for men and women, except that inability to work was missed most by all subjects. Only black men emphasized themselves, their jobs, and other persons as reasons for their disability. All subjects were most likely to cite mystical causes for their disability and to believe that mystical sources would most help them to improve."} {"id": "PMID:157116", "title": "Quantitative transcutaneous arterial velocity measurements with Doppler flowmeters.", "content": "A controlled in vitro and in vivo comparative evaluation of four Doppler ultrasonic blood velocimeters was performed to evaluate their ability to measure fluid velocity throughout a wide range of flow rates and velocity profiles, during both steady and pulsatile flow. The instruments tested were the Versatone Bidirectional Doppler M-9, the Sonicaid BV380, the Parks 806 B, and the Delalande DUD 400. All instruments responded linearly to velocities of from 5 to 70 cm/s, and were accurate to within 5% through a wide range of in vitro changes in velocity, pulse frequency, and cross-sectional velocity profile. Quantitative velocity measurements and their derivatives are an inexpensive, simple, and useful tool in the evaluation conditions of patients with peripheral vascular disease, and widespread clinical trials of their value are appropriate at this time.", "contents": "Quantitative transcutaneous arterial velocity measurements with Doppler flowmeters. A controlled in vitro and in vivo comparative evaluation of four Doppler ultrasonic blood velocimeters was performed to evaluate their ability to measure fluid velocity throughout a wide range of flow rates and velocity profiles, during both steady and pulsatile flow. The instruments tested were the Versatone Bidirectional Doppler M-9, the Sonicaid BV380, the Parks 806 B, and the Delalande DUD 400. All instruments responded linearly to velocities of from 5 to 70 cm/s, and were accurate to within 5% through a wide range of in vitro changes in velocity, pulse frequency, and cross-sectional velocity profile. Quantitative velocity measurements and their derivatives are an inexpensive, simple, and useful tool in the evaluation conditions of patients with peripheral vascular disease, and widespread clinical trials of their value are appropriate at this time."} {"id": "PMID:157117", "title": "A comparison of rapid-healing prosthetic arterial grafts and autogenous veins.", "content": "The patency rates and healing characteristics during a nine-month period of internal velour Dacron grafts, external velour Dacron grafts, and Sparks-Mandril grown grafts were compared with autogenous jugular veins when used to bypass short segments of the canine femoral artery. Graft thrombosis occurred in three of 11 external velour grafts, in six of 11 internal velour grafts, and in three of 11 Sparks-Mandril grafts, None of 33 autogenous veins occluded. Graft thrombosis was not correlated with the degree of graft healing but rather with a hyperplastic proliferative intimal lesion observed at the proximal anastomosis of the occluded grafts.", "contents": "A comparison of rapid-healing prosthetic arterial grafts and autogenous veins. The patency rates and healing characteristics during a nine-month period of internal velour Dacron grafts, external velour Dacron grafts, and Sparks-Mandril grown grafts were compared with autogenous jugular veins when used to bypass short segments of the canine femoral artery. Graft thrombosis occurred in three of 11 external velour grafts, in six of 11 internal velour grafts, and in three of 11 Sparks-Mandril grafts, None of 33 autogenous veins occluded. Graft thrombosis was not correlated with the degree of graft healing but rather with a hyperplastic proliferative intimal lesion observed at the proximal anastomosis of the occluded grafts."} {"id": "PMID:157114", "title": "[Anatomo-surgical considerations on the inguinal region. I. The external oblique muscle].", "content": "In the light of recent publications where common hernia repair techniques are defined as unanatomical and unphysiological, a study of the anatomy of the inguinal region has been undertaken layer by layer on cadavers. The first note analyses the most superficial layer of the inguinal region, namely the external oblique muscle. Having described the dissection technique, the most significant data regarding this formation are examined. Although the correctness of the data given in anatomy textbooks is confirmed in the majority of cases, study of necroptic findings highlights a number of factors which are misunderstood or have been insufficiently analysed. Findings included vibices of the external oblique aponeurosis, to which no pathogenetic importance is attributed with respect to inguinal hernia, as well as the presence of an internal tunic of Lauth's ligament which was not easy to strip away from the posterior surface of the external oblique muscle and, finally, localization variations of the external inguinal ring. The secondary involvement of the aponeurosis of the external oblique muscle in the genesis of inguinal hernia is confirmed along with its importance as a reinforcement in hernia repair operations, the containment function proper being performed by the posterior wall. A subsequent note will deal with this.", "contents": "[Anatomo-surgical considerations on the inguinal region. I. The external oblique muscle]. In the light of recent publications where common hernia repair techniques are defined as unanatomical and unphysiological, a study of the anatomy of the inguinal region has been undertaken layer by layer on cadavers. The first note analyses the most superficial layer of the inguinal region, namely the external oblique muscle. Having described the dissection technique, the most significant data regarding this formation are examined. Although the correctness of the data given in anatomy textbooks is confirmed in the majority of cases, study of necroptic findings highlights a number of factors which are misunderstood or have been insufficiently analysed. Findings included vibices of the external oblique aponeurosis, to which no pathogenetic importance is attributed with respect to inguinal hernia, as well as the presence of an internal tunic of Lauth's ligament which was not easy to strip away from the posterior surface of the external oblique muscle and, finally, localization variations of the external inguinal ring. The secondary involvement of the aponeurosis of the external oblique muscle in the genesis of inguinal hernia is confirmed along with its importance as a reinforcement in hernia repair operations, the containment function proper being performed by the posterior wall. A subsequent note will deal with this."} {"id": "PMID:157118", "title": "Correlation of liver growth and function during liver regeneration and hepatocarcinogenesis.", "content": "We have previously studied some parameters of rat liver activity and compared the kinetics of cell proliferation (normal growth or after partial hepatectomy) with some specific hepatic enzymes. The mutually exclusive relationship between division and tissue function, their specific circadian rhythm as well as the \"chalone effect\" have been used to characterize the normal homeostatic regulatory mechanism in the liver. The same parameters have been recently determined during chemical carcinogenesis. Adult rats, fed long term with diethylnitrosamine (DENA, 10 mg/kg/day) develop liver carcinoma after 90 days of carcinogen administration. The results show that the relationship between the above parameters is progressively disturbed during the second month of treatment. A minimum of 4 weeks of continuous DENA feeding is found to be necessary for the induction of liver cancers. Giving the carcinogen for a second month decreases the delay before death with cancer. Protracting the treatment after the second month has no further effect either on survival or on cancer induction. The mechanism of carcinogenesis is explained by postulating that preneoplastic lesions evolution would closely depend on the homeostatic control disturbances.", "contents": "Correlation of liver growth and function during liver regeneration and hepatocarcinogenesis. We have previously studied some parameters of rat liver activity and compared the kinetics of cell proliferation (normal growth or after partial hepatectomy) with some specific hepatic enzymes. The mutually exclusive relationship between division and tissue function, their specific circadian rhythm as well as the \"chalone effect\" have been used to characterize the normal homeostatic regulatory mechanism in the liver. The same parameters have been recently determined during chemical carcinogenesis. Adult rats, fed long term with diethylnitrosamine (DENA, 10 mg/kg/day) develop liver carcinoma after 90 days of carcinogen administration. The results show that the relationship between the above parameters is progressively disturbed during the second month of treatment. A minimum of 4 weeks of continuous DENA feeding is found to be necessary for the induction of liver cancers. Giving the carcinogen for a second month decreases the delay before death with cancer. Protracting the treatment after the second month has no further effect either on survival or on cancer induction. The mechanism of carcinogenesis is explained by postulating that preneoplastic lesions evolution would closely depend on the homeostatic control disturbances."} {"id": "PMID:157119", "title": "Comparison of the acute toxicity of clioquinol, histamine, and chloroform in different strains of mice.", "content": "The oral LD50'S of clioquinol, histamine and chloroform and the intravenous LD50 of histamine were determined separately in male and female mice of the Tif : MAGf (SPF), Tif : MF2f (SPF), C3H/Tif Bomf, DBA2/J Bomf, C57Bl/6J/Bomf and A/J Bomf strains. Mice of the Tif : MAGf (SPF) outbred strain and the Tif : MF2f(SPF) hybrids tended to be more resistant than the inbred strains, with exception of C57Bl/6J/Bomf, which proved least susceptible to the lethal effects of the tested preparations. The toxicity of chloroform was more pronounced in the males than in the females, and C3H/Tif Bomf proved more susceptible than all other strains. The toxicity of clioquinol and histamine was not related to sex.", "contents": "Comparison of the acute toxicity of clioquinol, histamine, and chloroform in different strains of mice. The oral LD50'S of clioquinol, histamine and chloroform and the intravenous LD50 of histamine were determined separately in male and female mice of the Tif : MAGf (SPF), Tif : MF2f (SPF), C3H/Tif Bomf, DBA2/J Bomf, C57Bl/6J/Bomf and A/J Bomf strains. Mice of the Tif : MAGf (SPF) outbred strain and the Tif : MF2f(SPF) hybrids tended to be more resistant than the inbred strains, with exception of C57Bl/6J/Bomf, which proved least susceptible to the lethal effects of the tested preparations. The toxicity of chloroform was more pronounced in the males than in the females, and C3H/Tif Bomf proved more susceptible than all other strains. The toxicity of clioquinol and histamine was not related to sex."} {"id": "PMID:157115", "title": "[Anatomo-surgical considerations on the inguinal region. II. The internal oblique muscle and transverse muscle].", "content": "Following a previous note on the musculus obliquus externus, attention is now directed to the obliques internus and the transversus in an assessment of the anatomical formations of the groin, in the light of doubts concerning their constitution expressed in the recent literature, and in a critical appraisal of the hernioplasty techniques proposed. Data from the cadaver, which appear to be of particular interest, show muscle-aponeurosis fissures in both the obliquus parvus and the obliquus externus; these may be the cause of recurrent hernias. The differences in the extent of the muscle and aponeurosis portions of the obliquus internus and the greater or lesser area of the trigonum inguinale, which is covered by aponeurotic fibres of the transversus, are regarded as important factors in the genesis of inguinal hernia.", "contents": "[Anatomo-surgical considerations on the inguinal region. II. The internal oblique muscle and transverse muscle]. Following a previous note on the musculus obliquus externus, attention is now directed to the obliques internus and the transversus in an assessment of the anatomical formations of the groin, in the light of doubts concerning their constitution expressed in the recent literature, and in a critical appraisal of the hernioplasty techniques proposed. Data from the cadaver, which appear to be of particular interest, show muscle-aponeurosis fissures in both the obliquus parvus and the obliquus externus; these may be the cause of recurrent hernias. The differences in the extent of the muscle and aponeurosis portions of the obliquus internus and the greater or lesser area of the trigonum inguinale, which is covered by aponeurotic fibres of the transversus, are regarded as important factors in the genesis of inguinal hernia."} {"id": "PMID:157121", "title": "[Drug-induced bullous dermatitis - Lyell's syndrome].", "content": "Three section observations of drug dermatitis which had developed against the background of treatment of acute respiratory diseases (Lyiell's syndrome) with sulphamides, antibiotics, and aspirin are presented.", "contents": "[Drug-induced bullous dermatitis - Lyell's syndrome]. Three section observations of drug dermatitis which had developed against the background of treatment of acute respiratory diseases (Lyiell's syndrome) with sulphamides, antibiotics, and aspirin are presented."} {"id": "PMID:157124", "title": "Current status of sterilization.", "content": "About 50 per cent of child bearing women in Australia are being sterilized. The selection of patients for the procedure requires careful counseling in order to avoid the risk of regret. Factors increasing the risk of regret are enumerated. Laparoscopy is the most popular method for sterilization, but mini laparotomy is a reasonable alternative for patients not having access to skilled laparoscopists. Clips and rings provide a greater chance of successful reversal of sterilization, and are recommended for use in younger women. The sequelae of sterilization are slight, with failure of technique, infection and temporary regret being the commonest. Serious psychological or physical sequelae are rare. If reversal is required the microsurgical technique is recommended.", "contents": "Current status of sterilization. About 50 per cent of child bearing women in Australia are being sterilized. The selection of patients for the procedure requires careful counseling in order to avoid the risk of regret. Factors increasing the risk of regret are enumerated. Laparoscopy is the most popular method for sterilization, but mini laparotomy is a reasonable alternative for patients not having access to skilled laparoscopists. Clips and rings provide a greater chance of successful reversal of sterilization, and are recommended for use in younger women. The sequelae of sterilization are slight, with failure of technique, infection and temporary regret being the commonest. Serious psychological or physical sequelae are rare. If reversal is required the microsurgical technique is recommended."} {"id": "PMID:157125", "title": "Comparison between saphenous vein and Dacron Velour grafts for femoropopliteal bypass.", "content": "One hundred and thirty-eight femoropopliteal grafts were performed for arteriosclerotic occlusive disease of the femoral artery in a five-year period. One group of patients who had 81 saphenous vein grafts was compared with a similar group who had 57 Dacron Velour grafts. At three years 90% of the vein grafts were patent, compared to 45% of the Dacron Velour grafts. Twenty-seven per cent of all patients presented with threatenened limb loss. Amputation was averted in all but 5%. Intraoperative flow measurement did not prove to be a reliable indicator of long-term patency.", "contents": "Comparison between saphenous vein and Dacron Velour grafts for femoropopliteal bypass. One hundred and thirty-eight femoropopliteal grafts were performed for arteriosclerotic occlusive disease of the femoral artery in a five-year period. One group of patients who had 81 saphenous vein grafts was compared with a similar group who had 57 Dacron Velour grafts. At three years 90% of the vein grafts were patent, compared to 45% of the Dacron Velour grafts. Twenty-seven per cent of all patients presented with threatenened limb loss. Amputation was averted in all but 5%. Intraoperative flow measurement did not prove to be a reliable indicator of long-term patency."} {"id": "PMID:157126", "title": "Axillofemoral arterial bypass grafts.", "content": "The results of 24 axillofemoral arterial bypass grafts performed over a five-year period are presented. This extraanatomical technique of arterial reconstruction is valuable following removal of an infected aortic Dacron graft and for limb salvage or severe intermittent claudication in selected poor-risk patients with aortoiliac occlusive disease. There were few early patency rate was excellent, but the long-term success of the operation is uncertain.", "contents": "Axillofemoral arterial bypass grafts. The results of 24 axillofemoral arterial bypass grafts performed over a five-year period are presented. This extraanatomical technique of arterial reconstruction is valuable following removal of an infected aortic Dacron graft and for limb salvage or severe intermittent claudication in selected poor-risk patients with aortoiliac occlusive disease. There were few early patency rate was excellent, but the long-term success of the operation is uncertain."} {"id": "PMID:157122", "title": "Quantifying auditory handicap. A new approach.", "content": "This report describes a new audiovisual test procedure for the quantification of auditory handicap (QUAH). The QUAH test attempts to recreate in the laboratory a series of everyday listening situations. Individual test items represent psychomotor tasks. Data on 53 normal-hearing listeners described performance as a function of the message-to-competition ratio (MCR). Results indicated that, for further studies, an MCR of 0 dB represents the condition above which the task seemed too easy and below which the task appeared too difficult for normal-hearing subjects. The QUAH approach to the measurement of auditory handicap seems promising as an experimental tool. Further studies are needed to describe the relation of QUAH results (1) to clinical audiologic measures and (2) to more traditional indices of auditory handicap.", "contents": "Quantifying auditory handicap. A new approach. This report describes a new audiovisual test procedure for the quantification of auditory handicap (QUAH). The QUAH test attempts to recreate in the laboratory a series of everyday listening situations. Individual test items represent psychomotor tasks. Data on 53 normal-hearing listeners described performance as a function of the message-to-competition ratio (MCR). Results indicated that, for further studies, an MCR of 0 dB represents the condition above which the task seemed too easy and below which the task appeared too difficult for normal-hearing subjects. The QUAH approach to the measurement of auditory handicap seems promising as an experimental tool. Further studies are needed to describe the relation of QUAH results (1) to clinical audiologic measures and (2) to more traditional indices of auditory handicap."} {"id": "PMID:157127", "title": "Aortoiliac occlusive vascular disease: a prospective study of patients treated by endarterectomy and bypass procedures.", "content": "Aortiliac occlusive vascular disease is very common and very disabling. A prospective study of 150 patients with the disease causing severe claudication and rest pain was begun in 1972, with a mimimum follow-up period of three years. An operative mortality of 2% and hospital morbidity of 14% can be obtained with attention to the broad principles of arterial reconstruction and a meticulous technique, provided that there is excellent anaesthetic, operative, and postoperative support. Severe complications or adverse episodes have occurred in 44% of patients who continued to smoke after their operation, as opposed to 28% in those who stopped. Frequent follow-up visits of 96% of patients have led to the early detection of significant vascular disease elsewhere in some patients, and this may be of importance in determining the eventual prognosis of this serious disease.", "contents": "Aortoiliac occlusive vascular disease: a prospective study of patients treated by endarterectomy and bypass procedures. Aortiliac occlusive vascular disease is very common and very disabling. A prospective study of 150 patients with the disease causing severe claudication and rest pain was begun in 1972, with a mimimum follow-up period of three years. An operative mortality of 2% and hospital morbidity of 14% can be obtained with attention to the broad principles of arterial reconstruction and a meticulous technique, provided that there is excellent anaesthetic, operative, and postoperative support. Severe complications or adverse episodes have occurred in 44% of patients who continued to smoke after their operation, as opposed to 28% in those who stopped. Frequent follow-up visits of 96% of patients have led to the early detection of significant vascular disease elsewhere in some patients, and this may be of importance in determining the eventual prognosis of this serious disease."} {"id": "PMID:157123", "title": "Psychological and social aspects of the evaluation of acquired hearing impairment.", "content": "From the literature, it is clear that handicap secondary to acquired hearing impairment has received limited research attention, and that the available studies are limited both in their choice of subjects, and in the adequacy of their audiological information. However, despite obvious deviations of these samples from what is known of the incidence and distribution of acquired hearing impairment, the generalisations of the investigators have in most instances been continued without comment or reservation by those citing their results. The implications of this limited viewpoint are discussed.", "contents": "Psychological and social aspects of the evaluation of acquired hearing impairment. From the literature, it is clear that handicap secondary to acquired hearing impairment has received limited research attention, and that the available studies are limited both in their choice of subjects, and in the adequacy of their audiological information. However, despite obvious deviations of these samples from what is known of the incidence and distribution of acquired hearing impairment, the generalisations of the investigators have in most instances been continued without comment or reservation by those citing their results. The implications of this limited viewpoint are discussed."} {"id": "PMID:157128", "title": "A surgical technique for the collection of cervical mucus in the ewe.", "content": "A technique for collecting cervical mucus in ewes is described. By a surgical procedure, the cervix was fixed to the ventral abdominal wall to enable mucus to be collected continuously into a container attached to the ewe. Mucus was collected successfully by this method for up to 14 months.", "contents": "A surgical technique for the collection of cervical mucus in the ewe. A technique for collecting cervical mucus in ewes is described. By a surgical procedure, the cervix was fixed to the ventral abdominal wall to enable mucus to be collected continuously into a container attached to the ewe. Mucus was collected successfully by this method for up to 14 months."} {"id": "PMID:157138", "title": "Relationship of raised atherosclerotic lesions to fatty streaks in coronary heart disease and hypertension.", "content": "The abdominal aortas and right coronary arteries removed during autopsies were gathered from over 18,000 subjects in 19 location-race groups. Sudanstained intimal surfaces were graded for the percent as raised lesions (R) and fatty streaks (F). The proportions of all types of lesions (ATL = F + R) that were raised (RaL = R divided by ATL) were examined. The difference between the observed RaL (in subjects having atherosclerosis-related conditions) and the expected RaL (in age-, sex-, and ATL-matched subjects without such conditions) measured the excess of RaL, which by inference indicated the tendency for an excess of raised lesions to be produced in place of fatty streaks. In cases of coronary heart disease (CHD), a large excess of RaL was found consistently on the average. The coronary arteries and aortas of hypertensive subjects, compared with those of nonhypertensives, had only a small and inconsistent excess of RaL. Both CHD and hypertension were characterized by a marked tendency for severe involvement by ATL, including extensive fatty streaks, leaving only small remnants of normal intima. Some factors (Class A) act to form fatty streaks and also to continue advancing them into raised lesions. Once the fatty streaks are formed, some new factors (Class B2) convert them into raised lesions. We concluded that hypertension is almost, if not entirely, a Class A type of atherogenic agent, and that CHD is promoted by exceptionally strong effects of both A and B2 types of causation. This conclusion exposes a biological priniciple that, if the assumptions of the model are true, is of considerable importance: Some of the more important causes of atherosclerosis (Class B causes) begin to act only after the fatty streaks have formed.", "contents": "Relationship of raised atherosclerotic lesions to fatty streaks in coronary heart disease and hypertension. The abdominal aortas and right coronary arteries removed during autopsies were gathered from over 18,000 subjects in 19 location-race groups. Sudanstained intimal surfaces were graded for the percent as raised lesions (R) and fatty streaks (F). The proportions of all types of lesions (ATL = F + R) that were raised (RaL = R divided by ATL) were examined. The difference between the observed RaL (in subjects having atherosclerosis-related conditions) and the expected RaL (in age-, sex-, and ATL-matched subjects without such conditions) measured the excess of RaL, which by inference indicated the tendency for an excess of raised lesions to be produced in place of fatty streaks. In cases of coronary heart disease (CHD), a large excess of RaL was found consistently on the average. The coronary arteries and aortas of hypertensive subjects, compared with those of nonhypertensives, had only a small and inconsistent excess of RaL. Both CHD and hypertension were characterized by a marked tendency for severe involvement by ATL, including extensive fatty streaks, leaving only small remnants of normal intima. Some factors (Class A) act to form fatty streaks and also to continue advancing them into raised lesions. Once the fatty streaks are formed, some new factors (Class B2) convert them into raised lesions. We concluded that hypertension is almost, if not entirely, a Class A type of atherogenic agent, and that CHD is promoted by exceptionally strong effects of both A and B2 types of causation. This conclusion exposes a biological priniciple that, if the assumptions of the model are true, is of considerable importance: Some of the more important causes of atherosclerosis (Class B causes) begin to act only after the fatty streaks have formed."} {"id": "PMID:157139", "title": "[Distribution of Mg-activated ATPase activity in the sensorimotor cortex (electron-cytochemical study)].", "content": "The localization of Mg-activated ATPase was studied by the lead method. The reaction product was seen in the nuclei and nucleoli of the cells. Five types of its distribution in the nuclei, typical for different types of cells and characterizing their functional activity were distinguished. The reaction to ATPase was also determined in the ribosomes, lipofuscin granules and some oval areas of the cytoplasma of cellular bodies and axons. The precipitate in the brain mitochondria was detected only after the administration of aminazine (15 mg/kg), i. e. in conditions of increased membrane permeability. The presence of ATPase reaction products in axo-dendrite synapses of different types, where it is mainly bound with postsynaptical consolidation and reflects the size of zone activity contacts, may have a direct relation to the conduction of the nervous impulse. The reaction product is also constantly present in the basal membrane of blood vessels.", "contents": "[Distribution of Mg-activated ATPase activity in the sensorimotor cortex (electron-cytochemical study)]. The localization of Mg-activated ATPase was studied by the lead method. The reaction product was seen in the nuclei and nucleoli of the cells. Five types of its distribution in the nuclei, typical for different types of cells and characterizing their functional activity were distinguished. The reaction to ATPase was also determined in the ribosomes, lipofuscin granules and some oval areas of the cytoplasma of cellular bodies and axons. The precipitate in the brain mitochondria was detected only after the administration of aminazine (15 mg/kg), i. e. in conditions of increased membrane permeability. The presence of ATPase reaction products in axo-dendrite synapses of different types, where it is mainly bound with postsynaptical consolidation and reflects the size of zone activity contacts, may have a direct relation to the conduction of the nervous impulse. The reaction product is also constantly present in the basal membrane of blood vessels."} {"id": "PMID:157141", "title": "[Chronic arsenic poisoning].", "content": "A case of chronic arsenic intoxication due to ingestion of contaminated water for several years is reported. The main symptoms were keratosis palmaris et plantaris, confetti - Like dyschromias in chest, post - necrotic liver cirrhosis multiple intraepithelial epidermoid carcinomas and invasive epidermoid carcinoma. The epidemiologic study showed high concentration of arsenic in the water of the well used by the patient; likewise, chronic arsenicalism was found in the whole family and in several neighbors who consumed water from the same well.", "contents": "[Chronic arsenic poisoning]. A case of chronic arsenic intoxication due to ingestion of contaminated water for several years is reported. The main symptoms were keratosis palmaris et plantaris, confetti - Like dyschromias in chest, post - necrotic liver cirrhosis multiple intraepithelial epidermoid carcinomas and invasive epidermoid carcinoma. The epidemiologic study showed high concentration of arsenic in the water of the well used by the patient; likewise, chronic arsenicalism was found in the whole family and in several neighbors who consumed water from the same well."} {"id": "PMID:157145", "title": "Blood volume in angina pectoris.", "content": "Blood volume was measured in 60 consecutive male patients with disabling angina pectoris undergoing preoperative investigation for coronary bypass surgery. Of these patients, 58 had a lower blood volume than predicted. There was a decrease in blood volume of 21% (1.3 litres) from the predicted normal value (P less than 0.001). Seventeen per cent of the patients were on diuretics, 30% were on digitalis, and 48% were on beta-blocking drugs at the time of the study. There was no correlation between this medical treatment and the deviation in blood volume. In patients without signs of myocardial insufficiency the decrease in blood volume was most prominent, while in those with an enlarged heart and a raised left ventricular preload (at rest) the deviation was less.", "contents": "Blood volume in angina pectoris. Blood volume was measured in 60 consecutive male patients with disabling angina pectoris undergoing preoperative investigation for coronary bypass surgery. Of these patients, 58 had a lower blood volume than predicted. There was a decrease in blood volume of 21% (1.3 litres) from the predicted normal value (P less than 0.001). Seventeen per cent of the patients were on diuretics, 30% were on digitalis, and 48% were on beta-blocking drugs at the time of the study. There was no correlation between this medical treatment and the deviation in blood volume. In patients without signs of myocardial insufficiency the decrease in blood volume was most prominent, while in those with an enlarged heart and a raised left ventricular preload (at rest) the deviation was less."} {"id": "PMID:157146", "title": "Hypertrophic cardiomyopathy associated with sudden death during marathon racing.", "content": "An experienced marathon runner died suddenly during a competitive race. At necropsy, ventricular hypertrophy but no asymmetrical septal hypertrophy was found. Histological studies showed features of hypertrophic cardiomyopathy. The coronary arteries were normal. We propose that the runner died from myocardial ischaemia, precipitated by marathon running on a background of hypertrophic cardiomyopathy. Excess cardiac work, induced by marathon running in the presence of mild congenital cardiac defects, could have contributed to the development of the cardiomyopathy.", "contents": "Hypertrophic cardiomyopathy associated with sudden death during marathon racing. An experienced marathon runner died suddenly during a competitive race. At necropsy, ventricular hypertrophy but no asymmetrical septal hypertrophy was found. Histological studies showed features of hypertrophic cardiomyopathy. The coronary arteries were normal. We propose that the runner died from myocardial ischaemia, precipitated by marathon running on a background of hypertrophic cardiomyopathy. Excess cardiac work, induced by marathon running in the presence of mild congenital cardiac defects, could have contributed to the development of the cardiomyopathy."} {"id": "PMID:157147", "title": "Heart size and function in acromegaly.", "content": "Cardiac size and function was studied in 23 acromegalic patients using echocardiography and systolic time interval measurements. Thirteen patients (56%) had increased left ventricular mass, and in the 20 treated patients this correlated well with the mean of the recent basal growth hormone levels. It is suggested that myocardial hypertrophy may regress in proportion to the degree of control of growth hormone levels. The ejection fraction was normal in all patients except one, and increased left ventricular mass was not associated with detectable impairment of left ventricular performance. Thus, most acromegalic hearts function normally even when their mass is considerably increased, though the long-term effects of this are unknown, Echocardiography will be valuable in the serial monitoring of the cardiac effects of acromegaly.", "contents": "Heart size and function in acromegaly. Cardiac size and function was studied in 23 acromegalic patients using echocardiography and systolic time interval measurements. Thirteen patients (56%) had increased left ventricular mass, and in the 20 treated patients this correlated well with the mean of the recent basal growth hormone levels. It is suggested that myocardial hypertrophy may regress in proportion to the degree of control of growth hormone levels. The ejection fraction was normal in all patients except one, and increased left ventricular mass was not associated with detectable impairment of left ventricular performance. Thus, most acromegalic hearts function normally even when their mass is considerably increased, though the long-term effects of this are unknown, Echocardiography will be valuable in the serial monitoring of the cardiac effects of acromegaly."} {"id": "PMID:157148", "title": "Relationship between hypertension and angina pectoris.", "content": "1 Many factors are of importance in the relationship between angina pectoris and hypertensive heart disease. Vascular resistance modifies the oxygen supply, whereas the oxygen demand is influenced by the systolic and diastolic BPs, the diastolic filling time and wall tension, the duration of systole and transmural pressure and the sympathetic stimulation to the heart. 2 The treatment of angina pectoris in patients with hypertensive heart disease should aim to reduce myocardial ischaemia, and it is suggested that beta-adrenoceptor antagonists are most suitable, as they reduce BP, heart rate and myocardial contractility and thus oxygen demand.", "contents": "Relationship between hypertension and angina pectoris. 1 Many factors are of importance in the relationship between angina pectoris and hypertensive heart disease. Vascular resistance modifies the oxygen supply, whereas the oxygen demand is influenced by the systolic and diastolic BPs, the diastolic filling time and wall tension, the duration of systole and transmural pressure and the sympathetic stimulation to the heart. 2 The treatment of angina pectoris in patients with hypertensive heart disease should aim to reduce myocardial ischaemia, and it is suggested that beta-adrenoceptor antagonists are most suitable, as they reduce BP, heart rate and myocardial contractility and thus oxygen demand."} {"id": "PMID:157149", "title": "Thiamphenicol and lupus nephritis. The effects of long-term therapy on kidney function and pathology: a pilot study.", "content": "NZB x OUW F1 hybrid mice were treated with thiamphenicol at 25, 50 and 250 mg/kg/day from the time of their first positive antinuclear antibody test until their death. Untreated mice fed the same diet served as controls with body weight, mortality and renal disease patterns conforming to published reports of the biology of the BW mice. Regular testing of urine and bloodm and detailed postmortem examinations showed (a) that with increasing drug dose levels heavy proteinuria was almost eliminated and blood urea concentrations significantly lowered; (b) that in treated and untreated mice moderate to severe anaemia developed, apparently unrelated to the degree of uraemia; (c) that changes in renal function did not correlate with antinuclear antibody activity, nor did the drop in packed cell volume correlate with fixed or free circulating antierythrocyte autoantibody positivity; (d) that histological analysis of renal changes showed that at the highest dose level glomerular lesions were minimal. Thus the prolonged treatment with thiamphenicol reduced the severity of the spontaneous renal disease and resulted in a significant extension of lifespan.", "contents": "Thiamphenicol and lupus nephritis. The effects of long-term therapy on kidney function and pathology: a pilot study. NZB x OUW F1 hybrid mice were treated with thiamphenicol at 25, 50 and 250 mg/kg/day from the time of their first positive antinuclear antibody test until their death. Untreated mice fed the same diet served as controls with body weight, mortality and renal disease patterns conforming to published reports of the biology of the BW mice. Regular testing of urine and bloodm and detailed postmortem examinations showed (a) that with increasing drug dose levels heavy proteinuria was almost eliminated and blood urea concentrations significantly lowered; (b) that in treated and untreated mice moderate to severe anaemia developed, apparently unrelated to the degree of uraemia; (c) that changes in renal function did not correlate with antinuclear antibody activity, nor did the drop in packed cell volume correlate with fixed or free circulating antierythrocyte autoantibody positivity; (d) that histological analysis of renal changes showed that at the highest dose level glomerular lesions were minimal. Thus the prolonged treatment with thiamphenicol reduced the severity of the spontaneous renal disease and resulted in a significant extension of lifespan."} {"id": "PMID:157150", "title": "The effect of topically applied progesterone on sebum excretion rate.", "content": "There is evidence that anti-androgens may help in the treatment of acne vulgaris. We therefore performed a double-blind trial to assess the effect of topically applied progesterone on sebum excretion rate. Thirty-eight patients took part in the trial which was for 3 months. The preparation had no effect in males. However, a significant reduction in sebum excretion rate was found in females, the effect being maximal at the end of the second month. There was a significant loss of effect at the end of the third month and this was not related to deterioration of the progesterone preparation.", "contents": "The effect of topically applied progesterone on sebum excretion rate. There is evidence that anti-androgens may help in the treatment of acne vulgaris. We therefore performed a double-blind trial to assess the effect of topically applied progesterone on sebum excretion rate. Thirty-eight patients took part in the trial which was for 3 months. The preparation had no effect in males. However, a significant reduction in sebum excretion rate was found in females, the effect being maximal at the end of the second month. There was a significant loss of effect at the end of the third month and this was not related to deterioration of the progesterone preparation."} {"id": "PMID:157151", "title": "An improved rabbit ear model for assessing comedogenic substances.", "content": "A simplified comedogenic assay is described in which test materials are applied for 2 weeks to the ears of rabbits just external to the ear canal. Excised tissue is thus immersed in water at 60 degrees C for 2 min, yielding a sheet of epidermis with microcomedones attached. The magnitude of follicular hyperkeratosis is extracted with the stereomicroscope. Sixteen materials were evaluated by the new and old model which required histological sectioning. Agreement was excellent.", "contents": "An improved rabbit ear model for assessing comedogenic substances. A simplified comedogenic assay is described in which test materials are applied for 2 weeks to the ears of rabbits just external to the ear canal. Excised tissue is thus immersed in water at 60 degrees C for 2 min, yielding a sheet of epidermis with microcomedones attached. The magnitude of follicular hyperkeratosis is extracted with the stereomicroscope. Sixteen materials were evaluated by the new and old model which required histological sectioning. Agreement was excellent."} {"id": "PMID:157152", "title": "Bone lesions in systemic acne (acne fulminans).", "content": "An 18-year-old West Indian male presented with severe sternal pain and an exacerbation of facial acne. Radiographs of the sternum revealed several lytic lesions which appeared as hot areas on successive technetium bone scans. Painful areas over the right iliac crest and left greater trochanter likewise appeared as transient hot areas on successive scans. Histology of affected bone revealed reactive changes only. High dose prednisolone provided rapid alleviation of pain, which recurred on reducing the dose to less than 10 mg daily. Auto-immune complex disease has been considered the most likely aetiological mechanism of systemic acne (acne fulminans), but lytic lesions of bone have never previously been reported in auto-immune disorders.", "contents": "Bone lesions in systemic acne (acne fulminans). An 18-year-old West Indian male presented with severe sternal pain and an exacerbation of facial acne. Radiographs of the sternum revealed several lytic lesions which appeared as hot areas on successive technetium bone scans. Painful areas over the right iliac crest and left greater trochanter likewise appeared as transient hot areas on successive scans. Histology of affected bone revealed reactive changes only. High dose prednisolone provided rapid alleviation of pain, which recurred on reducing the dose to less than 10 mg daily. Auto-immune complex disease has been considered the most likely aetiological mechanism of systemic acne (acne fulminans), but lytic lesions of bone have never previously been reported in auto-immune disorders."} {"id": "PMID:157153", "title": "The effect of topical crude coal tar treatment on unstimulated hairless hamster skin.", "content": "Topical treatment of hairless hamster skin with crude coal tar has been shown to induce epidermal thickening, an increased labelling index in the basal cell layer, an elevation in NADP-dependent glucose-6-phosphate dehydrogenase activity throughout the epidermis, an increased squame count, comedo formation, and atrophy of the sebaceous glands. Ultraviolet light fluorescence microscopy of sections of treated skin suggests that the hair follicle is an important route for skin penetration by coal tar.", "contents": "The effect of topical crude coal tar treatment on unstimulated hairless hamster skin. Topical treatment of hairless hamster skin with crude coal tar has been shown to induce epidermal thickening, an increased labelling index in the basal cell layer, an elevation in NADP-dependent glucose-6-phosphate dehydrogenase activity throughout the epidermis, an increased squame count, comedo formation, and atrophy of the sebaceous glands. Ultraviolet light fluorescence microscopy of sections of treated skin suggests that the hair follicle is an important route for skin penetration by coal tar."} {"id": "PMID:157157", "title": "Tryptic proteolysis of coupling factor-latent ATPase from mycobacterium phlei. Theoretical modeling of structure-function relationships.", "content": "Trypsin treatment of solubilized coupling factor-latent ATPase from Mycobacterium phlei alters its subunit structure and functional properties. This coupling factor exhibits ATPase activity following trypsin treatment. Concurrently, both the ability of the enzyme to rebind to membranes depleted of coupling factor and its capacity for coupled phosphorylation are lost. The native alpha (64 000 dalton) subunit undergoes limited proteolytic digestion, and the delta (14 000 dalton) subunit is partially lost. During the course of tryptic proteolysis, the coupling factor molecule may exist in one of ten unique structural state (e.g. the native, ATPase-inactive molecule exists in the alpha alpha alpha state). Rigorous analysis of the experimental data by theoretical modeling provided information concerning the intermediate structural states leading to the fully ATPase-activated alpha\" alpha\" alpha\" state under different conditions of trypsin treatment. The theoretical models of structure-function relationships that best-represented the experimental data predicted that the native coupling factor molecule contains three copies of the alpha (64 000 dalton) form of the alpha subunit, that the alpha\" (58 000 dalton) alpha subunit species contributes maximally and the alpha' (61 000 dalton) form about half-maximally to ATPase activity, that membrane rebinding ability is proportional to the number of native alpha subunits in the enzyme, and that at least one native alpha subunit/molecule is required for full expression of coupled phosphorylation. These results indicate an essential role for the alpha subunit in the regulation of ATPase activity and in the ability of the solubilized coupling factor to rebind to depleted membranes.", "contents": "Tryptic proteolysis of coupling factor-latent ATPase from mycobacterium phlei. Theoretical modeling of structure-function relationships. Trypsin treatment of solubilized coupling factor-latent ATPase from Mycobacterium phlei alters its subunit structure and functional properties. This coupling factor exhibits ATPase activity following trypsin treatment. Concurrently, both the ability of the enzyme to rebind to membranes depleted of coupling factor and its capacity for coupled phosphorylation are lost. The native alpha (64 000 dalton) subunit undergoes limited proteolytic digestion, and the delta (14 000 dalton) subunit is partially lost. During the course of tryptic proteolysis, the coupling factor molecule may exist in one of ten unique structural state (e.g. the native, ATPase-inactive molecule exists in the alpha alpha alpha state). Rigorous analysis of the experimental data by theoretical modeling provided information concerning the intermediate structural states leading to the fully ATPase-activated alpha\" alpha\" alpha\" state under different conditions of trypsin treatment. The theoretical models of structure-function relationships that best-represented the experimental data predicted that the native coupling factor molecule contains three copies of the alpha (64 000 dalton) form of the alpha subunit, that the alpha\" (58 000 dalton) alpha subunit species contributes maximally and the alpha' (61 000 dalton) form about half-maximally to ATPase activity, that membrane rebinding ability is proportional to the number of native alpha subunits in the enzyme, and that at least one native alpha subunit/molecule is required for full expression of coupled phosphorylation. These results indicate an essential role for the alpha subunit in the regulation of ATPase activity and in the ability of the solubilized coupling factor to rebind to depleted membranes."} {"id": "PMID:157158", "title": "Lipid protein interactions in mitochondria. VII. A comparison of the effects of lipid removal and lipid perturbation of the kinetic properties of mitochondrial ATPase.", "content": "We investigated the kinetics of mitochondrial ATPase in bovine heart mitochondria and submitochondrial particles upon treatment with phospholipase A2, or upon addition of n-butanol to perturb the lipid protein interactions. The changes observed are the following: (1) Lipid removal or perturbation with butanol is accompanied by loss of ATPase activity with decrease of both V and of the KM for ATP. (2) There are changes of activation energy of ATPase activity at temperatures above the discontinuity normally observed for membrane-bound enzymes in mitochondria. In particular, butanol abolishes the discontinuity, and induces a constant activation energy of about 32 kcal/mol in the range 8--37 degrees C. (3) Butanol modifies the pH dependence of ATPase shifting the pH optimum from around 10 to less alkaline values. The optimum for Mg2+ concentrations is increased by the solvent. (4) Treatment with phospholipase A2 results in a removal of oligomycin-sensitive ATPase, whereas butanol addition prevents oligomycin inhibition of ATPase. (5) In beef heart mitochondria, a spin-labelled analog of the inhibitor, dicyclohexyl carbodiimide, did not show any change in environment upon butanol addition, unlike that found in mitochondria from Saccharomyces cerevisiae.", "contents": "Lipid protein interactions in mitochondria. VII. A comparison of the effects of lipid removal and lipid perturbation of the kinetic properties of mitochondrial ATPase. We investigated the kinetics of mitochondrial ATPase in bovine heart mitochondria and submitochondrial particles upon treatment with phospholipase A2, or upon addition of n-butanol to perturb the lipid protein interactions. The changes observed are the following: (1) Lipid removal or perturbation with butanol is accompanied by loss of ATPase activity with decrease of both V and of the KM for ATP. (2) There are changes of activation energy of ATPase activity at temperatures above the discontinuity normally observed for membrane-bound enzymes in mitochondria. In particular, butanol abolishes the discontinuity, and induces a constant activation energy of about 32 kcal/mol in the range 8--37 degrees C. (3) Butanol modifies the pH dependence of ATPase shifting the pH optimum from around 10 to less alkaline values. The optimum for Mg2+ concentrations is increased by the solvent. (4) Treatment with phospholipase A2 results in a removal of oligomycin-sensitive ATPase, whereas butanol addition prevents oligomycin inhibition of ATPase. (5) In beef heart mitochondria, a spin-labelled analog of the inhibitor, dicyclohexyl carbodiimide, did not show any change in environment upon butanol addition, unlike that found in mitochondria from Saccharomyces cerevisiae."} {"id": "PMID:157159", "title": "Limited proteolysis of coupling factor-latent ATPase from Mycobacterium phlei. Effects of different enzymes and modifying agents.", "content": "The activation of the coupling factor-latent ATPase enzyme by tryptic proteolysis may resemble the activation of many proenzymes by limited proteolysis. The beta (53 000 dalton) subunit of solubilized coupling factor-latent ATPase from Mycobacterium phlei was selectively lost in some trypsin-treated samples. Since a concomitant loss of ATPase activity was not observed, the beta subunit may not be essential for ATPase catalytic activity. Treatment of solubilized coupling factor with chymotrypsin rapidly produced an A'-type (61 000 dalton) species from the native alpha (64 000 dalton) subunits with partial activation of the APTase enzyme. Secondary chymotryptic cleavage yielded an A\"-type (58 000 dalton) species and a less-active enzyme. Storage of fresh coupling factor samples at -20degreeC in the presence of 4 mM MgCl2 with several freeze-thaw cycles resulted in loss of ATPase activity without apparent change in alpha subunit structure. Storage at 4 degrees C in the presence or absence of MgCl2 both decreased ATPase activity and generated A'-type alpha subunit species. Since presence was suspected. The peptide bonds first cleaved by trypsin, chymotrypsin, and the unknown protease are all apparantly located within the same small segment of alpha subunit polypeptide chain.", "contents": "Limited proteolysis of coupling factor-latent ATPase from Mycobacterium phlei. Effects of different enzymes and modifying agents. The activation of the coupling factor-latent ATPase enzyme by tryptic proteolysis may resemble the activation of many proenzymes by limited proteolysis. The beta (53 000 dalton) subunit of solubilized coupling factor-latent ATPase from Mycobacterium phlei was selectively lost in some trypsin-treated samples. Since a concomitant loss of ATPase activity was not observed, the beta subunit may not be essential for ATPase catalytic activity. Treatment of solubilized coupling factor with chymotrypsin rapidly produced an A'-type (61 000 dalton) species from the native alpha (64 000 dalton) subunits with partial activation of the APTase enzyme. Secondary chymotryptic cleavage yielded an A\"-type (58 000 dalton) species and a less-active enzyme. Storage of fresh coupling factor samples at -20degreeC in the presence of 4 mM MgCl2 with several freeze-thaw cycles resulted in loss of ATPase activity without apparent change in alpha subunit structure. Storage at 4 degrees C in the presence or absence of MgCl2 both decreased ATPase activity and generated A'-type alpha subunit species. Since presence was suspected. The peptide bonds first cleaved by trypsin, chymotrypsin, and the unknown protease are all apparantly located within the same small segment of alpha subunit polypeptide chain."} {"id": "PMID:157160", "title": "Stabilization of rat liver mitochondrial F1-adenosine triphosphatase during chloroform-induced solubilization.", "content": "1. Isolation of ATPase from rat liver submitochondrial particles by chloroform treatment requires the presence of ATP or ADP during enzyme solubilization. In the absence of adenine nucleotides the enzyme activity is very low although all protein components of F1-ATPase are released. The low concentrations of ATP or ADP required (5 microM) indicate that the high affinity nucleotide-binding sites are involved in enzyme stabilization. Other nucleotides tested (ITP, GTP, UTP, CTP) were found to be less effective. 2. Polyacrylamide gel electrophoresis and immunodiffusion in agar plates revealed that in the absence of adenine nucleotides a fraction of F1-ATPase released by chloroform treatment is split into fragments. The part of the dissociated enzyme molecule has a molecular weight identical with that of a beta-subunit of F1-ATPase. 3. Dissociation of the F1-ATPase molecule could also be prevented by aurovertin. 4. Crude F1-ATPase solubilized by chloroform treatment can be further purified by Sepharose 6B gel filtration. Specific ATPase activity of the purified enzyme was 90 mumol Pi/min per mg protein and the enzyme was composed of five protein subunits (alpha, beta, gamma, delta, epsilon) with molecular weights 58 000, 55 000, 28 000, 13 000 and 8000, respectively. 5. Chloroform-released F1-ATPase from rat liver mitochondria displayed immunochemical cross-reactivity with that isolated from beef heart mitochondria.", "contents": "Stabilization of rat liver mitochondrial F1-adenosine triphosphatase during chloroform-induced solubilization. 1. Isolation of ATPase from rat liver submitochondrial particles by chloroform treatment requires the presence of ATP or ADP during enzyme solubilization. In the absence of adenine nucleotides the enzyme activity is very low although all protein components of F1-ATPase are released. The low concentrations of ATP or ADP required (5 microM) indicate that the high affinity nucleotide-binding sites are involved in enzyme stabilization. Other nucleotides tested (ITP, GTP, UTP, CTP) were found to be less effective. 2. Polyacrylamide gel electrophoresis and immunodiffusion in agar plates revealed that in the absence of adenine nucleotides a fraction of F1-ATPase released by chloroform treatment is split into fragments. The part of the dissociated enzyme molecule has a molecular weight identical with that of a beta-subunit of F1-ATPase. 3. Dissociation of the F1-ATPase molecule could also be prevented by aurovertin. 4. Crude F1-ATPase solubilized by chloroform treatment can be further purified by Sepharose 6B gel filtration. Specific ATPase activity of the purified enzyme was 90 mumol Pi/min per mg protein and the enzyme was composed of five protein subunits (alpha, beta, gamma, delta, epsilon) with molecular weights 58 000, 55 000, 28 000, 13 000 and 8000, respectively. 5. Chloroform-released F1-ATPase from rat liver mitochondria displayed immunochemical cross-reactivity with that isolated from beef heart mitochondria."} {"id": "PMID:157161", "title": "Purification and properties of the latent F1-APTase of Micrococcus lysodeikticus.", "content": "The latent coupling factor (F1)-ATPase of Micrococcus lysodeikticus has been purified to homogeneity as determined by a number of criteria including, nondenaturing polyacrylamide gel electrophoresis, crossed immunoelectrophoresis and analytical ultracentrifugation. By inclusion of 1 mM phenylmethyl sulfonyl fluoride, a serine protease inhibitor, in the shock-wash step of release of F1 from the membranes, the spontaneous activation of both crude and purified ATPase by endogenous membrane protease(s) can be prevented, thereby yielding a highly latent ATPase preparation. Equilibrium ultracentrifugation of the latent ATPase gave a molecular weight of 400 000. The ATPase contained five different subunits alpha, beta, gamma, delta, and espsilon and their molecular weights determined by SDS-polyacrylamide gel electrophoresis were 60 000, 54 000, 37 000, 27 000 and 9000, respectively. The subunit composition was determined with 14C-labelled, F1-ATPase prepared from cells grown on medium containing [U-14C]-labelled algal protein hydrolysate. Within the limitations of this method the results tentatively suggest a subunit composition of 3 : 3 : 1 : 1 : 3.", "contents": "Purification and properties of the latent F1-APTase of Micrococcus lysodeikticus. The latent coupling factor (F1)-ATPase of Micrococcus lysodeikticus has been purified to homogeneity as determined by a number of criteria including, nondenaturing polyacrylamide gel electrophoresis, crossed immunoelectrophoresis and analytical ultracentrifugation. By inclusion of 1 mM phenylmethyl sulfonyl fluoride, a serine protease inhibitor, in the shock-wash step of release of F1 from the membranes, the spontaneous activation of both crude and purified ATPase by endogenous membrane protease(s) can be prevented, thereby yielding a highly latent ATPase preparation. Equilibrium ultracentrifugation of the latent ATPase gave a molecular weight of 400 000. The ATPase contained five different subunits alpha, beta, gamma, delta, and espsilon and their molecular weights determined by SDS-polyacrylamide gel electrophoresis were 60 000, 54 000, 37 000, 27 000 and 9000, respectively. The subunit composition was determined with 14C-labelled, F1-ATPase prepared from cells grown on medium containing [U-14C]-labelled algal protein hydrolysate. Within the limitations of this method the results tentatively suggest a subunit composition of 3 : 3 : 1 : 1 : 3."} {"id": "PMID:157162", "title": "Inactive to active transitions of the mitochondrial ATPase complex as controlled by the ATPase inhibitor.", "content": "The hydrolytic and phosphorylation activities of the ATPase complex of bovine heart mitochondria are regulated by the ATPase inhibitor of Pullman and Monroy [1]. The inhibiting action of the peptide on ATPase activity can be overcome by a proton-motive force. Submitochondrial particles that contain the inhibitor, either intrinsically or externally added, show a lag that precedes phosphorylation. Particles devoid of the inhibitor, of particles that are in an 'active' state fail to present the lag. Accordingly, the data indicate that, prior to the onset of phosphorylation, the ATPase complex undergoes a transition to an active state through a process that involves the inhibitor. The transition depends on the concentration of ATP, 50 microM ATP giving 50% inhibition of the proton-motive force-induced transition.", "contents": "Inactive to active transitions of the mitochondrial ATPase complex as controlled by the ATPase inhibitor. The hydrolytic and phosphorylation activities of the ATPase complex of bovine heart mitochondria are regulated by the ATPase inhibitor of Pullman and Monroy [1]. The inhibiting action of the peptide on ATPase activity can be overcome by a proton-motive force. Submitochondrial particles that contain the inhibitor, either intrinsically or externally added, show a lag that precedes phosphorylation. Particles devoid of the inhibitor, of particles that are in an 'active' state fail to present the lag. Accordingly, the data indicate that, prior to the onset of phosphorylation, the ATPase complex undergoes a transition to an active state through a process that involves the inhibitor. The transition depends on the concentration of ATP, 50 microM ATP giving 50% inhibition of the proton-motive force-induced transition."} {"id": "PMID:157163", "title": "Involvement of phosphate-modified ATP analogs in the reactions of oxidative phosphorylation.", "content": "Various analogs of adenosine 5'-triphosphate with a modified terminal phosphate group have been tested in energy-requiring reactions with intact mitochondria and submitochondrial particles. It is shown that the fluorophosphate analog ATP(gamma F) is a strong inhibitor of mitochondrial respiration and of energy requiring reactions which involve the participation of high energy intermediates, generated aerobically by the respiratory chain. On the other hand, ATP(gamma F) does not affect the ATPase activity of intact or disrupted mitochondria and is less effective in inhibiting ATP-driven reactions. The imidophosphate analog AMP-P(NH)P also inhibits the partial reactions of oxidative phosphorylation, but does not affect ATP synthesis from ADP and Pi. In contrast to ATP(gamma F), it is strong inhibitor of both soluble and membrane-bound mitochondrial ATPases. The biological implication of the complementary effects of ATP(gamma F) and AMP-P(NH)P on mitochondria-catalysed reactions is discussed while suggesting the use of such nucleotide analogs as specific tools for the study of ATP-forming and ATP-utilizing reactions in mitochondria.", "contents": "Involvement of phosphate-modified ATP analogs in the reactions of oxidative phosphorylation. Various analogs of adenosine 5'-triphosphate with a modified terminal phosphate group have been tested in energy-requiring reactions with intact mitochondria and submitochondrial particles. It is shown that the fluorophosphate analog ATP(gamma F) is a strong inhibitor of mitochondrial respiration and of energy requiring reactions which involve the participation of high energy intermediates, generated aerobically by the respiratory chain. On the other hand, ATP(gamma F) does not affect the ATPase activity of intact or disrupted mitochondria and is less effective in inhibiting ATP-driven reactions. The imidophosphate analog AMP-P(NH)P also inhibits the partial reactions of oxidative phosphorylation, but does not affect ATP synthesis from ADP and Pi. In contrast to ATP(gamma F), it is strong inhibitor of both soluble and membrane-bound mitochondrial ATPases. The biological implication of the complementary effects of ATP(gamma F) and AMP-P(NH)P on mitochondria-catalysed reactions is discussed while suggesting the use of such nucleotide analogs as specific tools for the study of ATP-forming and ATP-utilizing reactions in mitochondria."} {"id": "PMID:157164", "title": "Sulphydryl groups in photosynthetic energy conservation. V. Localization of the new disulfide bridges formed by o-iodosobenzoate in coupling factor of spinach chloroplasts.", "content": "1. Chemical modification by o-iodosobenzoate of soluble chloroplast coupling factor 1 (CF1) during heat activation resulted in inhibition of its Ca-ATPase activity and in the formation of two new intrapeptide disulfide bridges as suggested by: (a) the disappearance of three out of four accessible thiol groups, two from gamma and one from a beta subunit as a consequence of CF1 modification by o-iodosobenzoate; (b) the total free sulphydryl groups of CF1 were reduced from 8 to 4 after modification of CF1 by o-iodosobenzoate. Two groups disappeared from beta and two from gamma subunits; (c) a second heating step of CF1 in the presence of 10 mM dithioerythritol reversed the inhibition of the ATPase and reduced both the newly formed disulfide bridges and those present in native CF1. 2. Modification of chloroplasts in the light with o-iodosobenzoate resulted in the inhibition of photophosphorylation and ATPase. CF1 isolated and purified from these chloroplasts had its Ca-ATPase activity inhibited and two new disulfide bridges. The total number of free sulphydryl groups was reduced from 8 to 4 and three accessible groups disappeared from beta and gamma subunits.", "contents": "Sulphydryl groups in photosynthetic energy conservation. V. Localization of the new disulfide bridges formed by o-iodosobenzoate in coupling factor of spinach chloroplasts. 1. Chemical modification by o-iodosobenzoate of soluble chloroplast coupling factor 1 (CF1) during heat activation resulted in inhibition of its Ca-ATPase activity and in the formation of two new intrapeptide disulfide bridges as suggested by: (a) the disappearance of three out of four accessible thiol groups, two from gamma and one from a beta subunit as a consequence of CF1 modification by o-iodosobenzoate; (b) the total free sulphydryl groups of CF1 were reduced from 8 to 4 after modification of CF1 by o-iodosobenzoate. Two groups disappeared from beta and two from gamma subunits; (c) a second heating step of CF1 in the presence of 10 mM dithioerythritol reversed the inhibition of the ATPase and reduced both the newly formed disulfide bridges and those present in native CF1. 2. Modification of chloroplasts in the light with o-iodosobenzoate resulted in the inhibition of photophosphorylation and ATPase. CF1 isolated and purified from these chloroplasts had its Ca-ATPase activity inhibited and two new disulfide bridges. The total number of free sulphydryl groups was reduced from 8 to 4 and three accessible groups disappeared from beta and gamma subunits."} {"id": "PMID:157165", "title": "Activation of Thermus phosphofructokinase by monovalent cations.", "content": "The presence of the monovalent cations Tl+, NH+4, K+, Rb+ or Cs+, in decreasing order of potency, produce a marked equivalent increase in the specific enzyme activity of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) purified from extreme thermophile, Thermus X-1. By contrast, the monovalent cations Li+, Na+ or CH3NH+3 produce no detectable catalyitic activation at concentrations up to 100 mM. The relative potency of these cations suggests that each polypeptide chain in the tetrameric enzyme possesses a cationbinding site having tetragonal symmetry and that the protein ligands are principally hydroxyl or carboxylate oxygens. Only the enzyme-cation complex and not the enzyme by itself exhibits cooperativity with respect to the dependence of catalytic rate on the concentration of the substrate, fructose 6-phosphate. In the presence of subsaturating but not saturating concentrations of substrate, the catalytic activation produced by monovalent cations is also cooperative. Exclusion chromatographic measurements indicate that the enzyme remains tetrameric at catalytic concentrations in the presence or absence of an activating monovalent cation.", "contents": "Activation of Thermus phosphofructokinase by monovalent cations. The presence of the monovalent cations Tl+, NH+4, K+, Rb+ or Cs+, in decreasing order of potency, produce a marked equivalent increase in the specific enzyme activity of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) purified from extreme thermophile, Thermus X-1. By contrast, the monovalent cations Li+, Na+ or CH3NH+3 produce no detectable catalyitic activation at concentrations up to 100 mM. The relative potency of these cations suggests that each polypeptide chain in the tetrameric enzyme possesses a cationbinding site having tetragonal symmetry and that the protein ligands are principally hydroxyl or carboxylate oxygens. Only the enzyme-cation complex and not the enzyme by itself exhibits cooperativity with respect to the dependence of catalytic rate on the concentration of the substrate, fructose 6-phosphate. In the presence of subsaturating but not saturating concentrations of substrate, the catalytic activation produced by monovalent cations is also cooperative. Exclusion chromatographic measurements indicate that the enzyme remains tetrameric at catalytic concentrations in the presence or absence of an activating monovalent cation."} {"id": "PMID:157166", "title": "On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha2-antiplasmin and in fibrinogen.", "content": "Plasminogen and plasminogen derivatives which contain lysine-binding sites were found to decrease the reaction rate between plasmin and alpha2-antiplasmin by competing with plasmin for the complementary site(s) in alpha2-antiplasmin. The dissocwation constant Kd for the interaction between intact plasminogen (Glu-plasminogen) and alpha2-antiplasmin is 4.0 microM but those for Lys-plasminogen or TLCK-plasmin are about 10-fold lower indicating a stronger interaction. The lysine-binding site(s) which is situated in triple-loops 1--3 in the plasmin A-chain is mainly responsible for the interaction with alpha2-antiplasmin. The interaction between Glu-plasminogen and alpha2-antiplasmin furthermore enhances the activation of Glu-plasminogen by urokinase to a comparable extent as 6-aminohexanoic acid, suggesting that similar conformational changes occur in the proenzyme after complex formation. Fibrinogen, fibrinogen digested with plasmin, purified fragment E and purified fragment D interfere with the reaction between plasmin and alpha2-antiplasmin by competing with alpha2-antiplasmin for the lysine-binding site(s) in the plasmin A-chain. The Kd obtained for these interactions varied between 0.2 microM and 1.4 microM; fragment E being the most effective. Thus the fibrinogen molecule contains several complementary sites to the lysine-binding sites located both in its NH2-terminal and COOH-terminal regions; these sites are to a large extent.", "contents": "On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha2-antiplasmin and in fibrinogen. Plasminogen and plasminogen derivatives which contain lysine-binding sites were found to decrease the reaction rate between plasmin and alpha2-antiplasmin by competing with plasmin for the complementary site(s) in alpha2-antiplasmin. The dissocwation constant Kd for the interaction between intact plasminogen (Glu-plasminogen) and alpha2-antiplasmin is 4.0 microM but those for Lys-plasminogen or TLCK-plasmin are about 10-fold lower indicating a stronger interaction. The lysine-binding site(s) which is situated in triple-loops 1--3 in the plasmin A-chain is mainly responsible for the interaction with alpha2-antiplasmin. The interaction between Glu-plasminogen and alpha2-antiplasmin furthermore enhances the activation of Glu-plasminogen by urokinase to a comparable extent as 6-aminohexanoic acid, suggesting that similar conformational changes occur in the proenzyme after complex formation. Fibrinogen, fibrinogen digested with plasmin, purified fragment E and purified fragment D interfere with the reaction between plasmin and alpha2-antiplasmin by competing with alpha2-antiplasmin for the lysine-binding site(s) in the plasmin A-chain. The Kd obtained for these interactions varied between 0.2 microM and 1.4 microM; fragment E being the most effective. Thus the fibrinogen molecule contains several complementary sites to the lysine-binding sites located both in its NH2-terminal and COOH-terminal regions; these sites are to a large extent."} {"id": "PMID:157167", "title": "Some properties of Physarum actinin. A regulatory protein of actin polymerization.", "content": "A factor termed Physarum actinin was isolated and partially purified from plasmodia of a myxomycete, Physarum polycephalum. When Physarum actinin was mixed with purified Physarum or rabbit striated muscle G-actin in a weight ratio of about 1 actinin to 9 actin and then the polymerization of G-actin induced, G-actin polymerized to the ordinary F-actin on addition of 0.1 M KCl. However, it polymerized to Mg-polymer on addition of 2 mM MgCl2. The reduced viscosity (etasp/C) of the Mg-polymer was 1.2 dl/g, about one-seventh of that of the F-actin (7.4 dl/g). The sedimentation coefficient of the Mg-polymer was 22.8 S, almost the same as that of the F-actin (29.4 S). The Mg-polymer showed the specific ATPase activity of the order of 1 . 10(-3) mumol ATP/mg actin per min. It was shown that Physarum actinin copolymerized with G-actin to form Mg-polymer on addition of 2 mM MgCl2. The molecular weights of Physarum actinin were about 90 000 in salt-free or slat solutions and 43 000 in a dodecyl sulfate solution. The range of salting out with ammonium sulfate was 50--65% saturation, which was different from that of Physarum actin (15--35% saturation). Physarum actinin did not interact with Physarum myosin or muscle heavy meromyosin. When the weight ratio of actinin to actin increased, the flow birefringence of the formed Mg-polymer decreased, and it became almost zero at the weight ratio of 1 actinin to 5 actin. ATPase activity reached the maximum level (2.2 . 10(-3) mumol ATP/mg actin per min) at the same ratio. On the addition of Physarum actinin to purified Physarum F-actin which had been polymerized on addition of 2 mM MgCl2 the viscosity decreased rapidly, suggesting that the F-actin filaments were broken in the smaller fragments or that they transformed to Mg-polymers. A factor with properties similar to Physarum actinin was isolated from acetone powder of sea urchin eggs.", "contents": "Some properties of Physarum actinin. A regulatory protein of actin polymerization. A factor termed Physarum actinin was isolated and partially purified from plasmodia of a myxomycete, Physarum polycephalum. When Physarum actinin was mixed with purified Physarum or rabbit striated muscle G-actin in a weight ratio of about 1 actinin to 9 actin and then the polymerization of G-actin induced, G-actin polymerized to the ordinary F-actin on addition of 0.1 M KCl. However, it polymerized to Mg-polymer on addition of 2 mM MgCl2. The reduced viscosity (etasp/C) of the Mg-polymer was 1.2 dl/g, about one-seventh of that of the F-actin (7.4 dl/g). The sedimentation coefficient of the Mg-polymer was 22.8 S, almost the same as that of the F-actin (29.4 S). The Mg-polymer showed the specific ATPase activity of the order of 1 . 10(-3) mumol ATP/mg actin per min. It was shown that Physarum actinin copolymerized with G-actin to form Mg-polymer on addition of 2 mM MgCl2. The molecular weights of Physarum actinin were about 90 000 in salt-free or slat solutions and 43 000 in a dodecyl sulfate solution. The range of salting out with ammonium sulfate was 50--65% saturation, which was different from that of Physarum actin (15--35% saturation). Physarum actinin did not interact with Physarum myosin or muscle heavy meromyosin. When the weight ratio of actinin to actin increased, the flow birefringence of the formed Mg-polymer decreased, and it became almost zero at the weight ratio of 1 actinin to 5 actin. ATPase activity reached the maximum level (2.2 . 10(-3) mumol ATP/mg actin per min) at the same ratio. On the addition of Physarum actinin to purified Physarum F-actin which had been polymerized on addition of 2 mM MgCl2 the viscosity decreased rapidly, suggesting that the F-actin filaments were broken in the smaller fragments or that they transformed to Mg-polymers. A factor with properties similar to Physarum actinin was isolated from acetone powder of sea urchin eggs."} {"id": "PMID:157169", "title": "Studies of soluble rat liver mitochondrial acid ATPases. II. Structural and immunological properties of ATPase 1.", "content": "We described previously the existence of a soluble ATPase activity in rat liver mitochondria [1]. The purification and catalytic properties have been described [2]. In a continuation of these experiments, we have studied the immunologic and structural properties of one molecular form of this enzyme : ATPase I. We have prepared the antiserum anti-ATPase I and demonstrated the purity of our enzyme preparation by immunodiffusion and immunoelectrophoresis. An immunohistochemical method also confirmed the localization of ATPase I in the soluble fraction of mitochondria. The molecular weight of ATPase I was measured by G 100 Sephadex gel filtration and was found to be 18,400; electrophoresis on polyacrylamide gels gave a value of 18,600. The pHi of ATPase I was found to be 7,2. Amino acid analysis showed high amounts of aspartic acid, glutamic acid, serine and glycine. The molecular weight calculated from the total amino acid residues was found to be 17,000. Alanine is the NH2 terminal amino acid. The peptide maps obtained after degrading ATPase I with cyanogen bromide or trypsin are in accordance with the methionine, lysine and arginine residues we found in the ATPase I molecule. ATPase I does not appear to be a glycoprotein.", "contents": "Studies of soluble rat liver mitochondrial acid ATPases. II. Structural and immunological properties of ATPase 1. We described previously the existence of a soluble ATPase activity in rat liver mitochondria [1]. The purification and catalytic properties have been described [2]. In a continuation of these experiments, we have studied the immunologic and structural properties of one molecular form of this enzyme : ATPase I. We have prepared the antiserum anti-ATPase I and demonstrated the purity of our enzyme preparation by immunodiffusion and immunoelectrophoresis. An immunohistochemical method also confirmed the localization of ATPase I in the soluble fraction of mitochondria. The molecular weight of ATPase I was measured by G 100 Sephadex gel filtration and was found to be 18,400; electrophoresis on polyacrylamide gels gave a value of 18,600. The pHi of ATPase I was found to be 7,2. Amino acid analysis showed high amounts of aspartic acid, glutamic acid, serine and glycine. The molecular weight calculated from the total amino acid residues was found to be 17,000. Alanine is the NH2 terminal amino acid. The peptide maps obtained after degrading ATPase I with cyanogen bromide or trypsin are in accordance with the methionine, lysine and arginine residues we found in the ATPase I molecule. ATPase I does not appear to be a glycoprotein."} {"id": "PMID:157168", "title": "[Transmembrane potential formation upon ATP hydrolysis in sarcoplasmic reticulum].", "content": "Fluorescent cyanine (diS-C3-(5), diS-C2-(5), diO-C3-(5)) and oxonol (diBA-C4-(5)) potential-dependent dyes appeared to be extremely effective in detecting and studying the potential formed on the fragmented sarcoplasmic reticulum membrane under Ca2+ transport When [Ca2+] less than 5 X 10(-7) M ATP hydrolysis leads to formation of transmembrane potential (positive inside vesicules) caused by the Ca-independent ATPase activity. The potential is formed by a monovalent ion, presumably by H+, and possibly by Mg2+ ions. Ca-dependent ATPase activation by Ca2+ makes the potential to drop sharply and successive Ca2+ transport proceeds at low potential value. When Ca2+ has been accumulated by vesicules the Ca-independent ATPase restores positive potential. The potentials generated by both Ca-independent (10--30 mv) and Ca-dependent (-20 divided by -40 mv) ATPases have been estimated on the basis of the Nernst's equation with the help of positive and negative diffusion potentials formed by MgCl2 and CaCl2 gradients. The Ca2+ transport is shown not to be due to transmembrane electrophoresis but Ca-dependent ATPase action. The results suggest quite clearly that Ca-dependent ATPase operates as electrogenic Ca2+/H+, Mg2+-exchanger. The functional role of Ca-independent ATPase is, possibly, in compensation of charge effects when Ca2+ ions are passing through the membranes. The model illustrating the electrogenicity of Ca-independent and Ca-dependent ATPases action during Ca2+ transport in SR membranes has been proposed.", "contents": "[Transmembrane potential formation upon ATP hydrolysis in sarcoplasmic reticulum]. Fluorescent cyanine (diS-C3-(5), diS-C2-(5), diO-C3-(5)) and oxonol (diBA-C4-(5)) potential-dependent dyes appeared to be extremely effective in detecting and studying the potential formed on the fragmented sarcoplasmic reticulum membrane under Ca2+ transport When [Ca2+] less than 5 X 10(-7) M ATP hydrolysis leads to formation of transmembrane potential (positive inside vesicules) caused by the Ca-independent ATPase activity. The potential is formed by a monovalent ion, presumably by H+, and possibly by Mg2+ ions. Ca-dependent ATPase activation by Ca2+ makes the potential to drop sharply and successive Ca2+ transport proceeds at low potential value. When Ca2+ has been accumulated by vesicules the Ca-independent ATPase restores positive potential. The potentials generated by both Ca-independent (10--30 mv) and Ca-dependent (-20 divided by -40 mv) ATPases have been estimated on the basis of the Nernst's equation with the help of positive and negative diffusion potentials formed by MgCl2 and CaCl2 gradients. The Ca2+ transport is shown not to be due to transmembrane electrophoresis but Ca-dependent ATPase action. The results suggest quite clearly that Ca-dependent ATPase operates as electrogenic Ca2+/H+, Mg2+-exchanger. The functional role of Ca-independent ATPase is, possibly, in compensation of charge effects when Ca2+ ions are passing through the membranes. The model illustrating the electrogenicity of Ca-independent and Ca-dependent ATPases action during Ca2+ transport in SR membranes has been proposed."} {"id": "PMID:157172", "title": "Current status of biomaterial's clinical applications in plastic and reconstructive surgery.", "content": "The use of biomaterials as replacement parts is not new. The concept has fascinated physicians for thousands of years. Using gold plates to reconstruct defects in the skull over 3000 years ago constituted the early record in the literature of use of biomaterials in implantology. The recent advances in space age technology and in clinical biocompatibility has been a major contributing factor in introducing new materials for use as implantology polymers. However, the ideal implant is still not there, and whenever a major reconstruction is required consideration should be given first to the use of autogenous substitutes; when that is not available, then we should resort to inorganic substitutes.", "contents": "Current status of biomaterial's clinical applications in plastic and reconstructive surgery. The use of biomaterials as replacement parts is not new. The concept has fascinated physicians for thousands of years. Using gold plates to reconstruct defects in the skull over 3000 years ago constituted the early record in the literature of use of biomaterials in implantology. The recent advances in space age technology and in clinical biocompatibility has been a major contributing factor in introducing new materials for use as implantology polymers. However, the ideal implant is still not there, and whenever a major reconstruction is required consideration should be given first to the use of autogenous substitutes; when that is not available, then we should resort to inorganic substitutes."} {"id": "PMID:157173", "title": "Preliminary histologic evaluation of a biocompatible mesh for tracheal reconstruction.", "content": "The purpose of this study was to evaluate a porous Dacron - urethane mesh tracheal prosthesis in large dogs with surgically created discontinuous defects of the cervical trachea. Some protheses were carbon coated in an attempt to improve biocompatibility. Histology was performed on 2 dogs. The mucosa regenerated entirely covering the prosthesis. Respiratory epithelium was formed over a large central portion of the tracheas.", "contents": "Preliminary histologic evaluation of a biocompatible mesh for tracheal reconstruction. The purpose of this study was to evaluate a porous Dacron - urethane mesh tracheal prosthesis in large dogs with surgically created discontinuous defects of the cervical trachea. Some protheses were carbon coated in an attempt to improve biocompatibility. Histology was performed on 2 dogs. The mucosa regenerated entirely covering the prosthesis. Respiratory epithelium was formed over a large central portion of the tracheas."} {"id": "PMID:157176", "title": "[Stereological study of the absolute total volumes of the structural components of the myocardium in hypertrophy].", "content": "Wistar rats weighing 200 g were exposed in a low pressure chamber to daily adaptation to altitude hypoxia 8 hours long at an \"altitude\" of 8000 m. On the 40th experimental day the weight of the left heart ventricle was 41.5% higher as compared to controls. The volumetric and surface density of structural components of the myocardium were determined stereologically by light and electron microscopy, with their absolute total amounts and surfaces being calculated with respect to the ventricle on the whole. The total amount of myofibrila was shown to be steadily increased under hypertrophy, while the amount of mitochondria remained unchanged. However, the total mitochondrial surface augmented in parallel to an increase in the muscular component amount. It is suggested that myofibrillar amount and mitochondrial surface area may be viewed as controllable parameters in heart hypertrophy.", "contents": "[Stereological study of the absolute total volumes of the structural components of the myocardium in hypertrophy]. Wistar rats weighing 200 g were exposed in a low pressure chamber to daily adaptation to altitude hypoxia 8 hours long at an \"altitude\" of 8000 m. On the 40th experimental day the weight of the left heart ventricle was 41.5% higher as compared to controls. The volumetric and surface density of structural components of the myocardium were determined stereologically by light and electron microscopy, with their absolute total amounts and surfaces being calculated with respect to the ventricle on the whole. The total amount of myofibrila was shown to be steadily increased under hypertrophy, while the amount of mitochondria remained unchanged. However, the total mitochondrial surface augmented in parallel to an increase in the muscular component amount. It is suggested that myofibrillar amount and mitochondrial surface area may be viewed as controllable parameters in heart hypertrophy."} {"id": "PMID:157177", "title": "[Quantitative determination of the epidermal G2-chalonelike factor in rat tissues by means of radial immunodiffusion].", "content": "A high-molecular glycoprotein (epidermal G2 chalone) shown to be homogeneous by electrophoresis and immunochemistry was isolated from rat skin. It exerts a strong tissue-rather than species-specific antimitotic effect on the keratinizing epithelium. The paper is concerned with its quantitative immunodiffusion determination in some tissues by means of monospecific antiserum. A clear-cut correlation between the mitotic index and the epidermal G2 chalone level in the mucosa is shown with special reference to vaginal epithelium of rats during the estrual cycle.", "contents": "[Quantitative determination of the epidermal G2-chalonelike factor in rat tissues by means of radial immunodiffusion]. A high-molecular glycoprotein (epidermal G2 chalone) shown to be homogeneous by electrophoresis and immunochemistry was isolated from rat skin. It exerts a strong tissue-rather than species-specific antimitotic effect on the keratinizing epithelium. The paper is concerned with its quantitative immunodiffusion determination in some tissues by means of monospecific antiserum. A clear-cut correlation between the mitotic index and the epidermal G2 chalone level in the mucosa is shown with special reference to vaginal epithelium of rats during the estrual cycle."} {"id": "PMID:157179", "title": "A study of changes in the spine in weight lifters and other athletes.", "content": "The present study was undertaken in sportsmen of those groups of sports activities where weight training exercises constitute a major part of the training. Two groups consisting of 25 weight-lifters and 25 track and field athletes were studied to find out the effect of sports activities and lifting weights on the spine. 84% weight-lifters and 72% track and field athletes suffered from varying abnormalities. Incidence of backache in 25 weight-lifters was 40% and in 25 track and field athletes 48%. Radiological changes were more common in weight-lifters (84%) than in athletes (72%). Reduction in lumbar lordosis was found in three cases (12%) in both the groups. Obtuse angle deformity of vertebral margins was found in 11 cases (44%) amongst weight-lifters and six cases (24%) amongst athletes. Osteophytic formation was found in six cases (24%) in weight-lifters and four cases (16%) in athletes. Schmorl's node were noticed in five cases (20%) amongst weight-lifters and seven cases (28%) amongst athletes. The incidences of spondylosis and Schmorl's node were found only in those cases who had been doing weight training exercises for more than four years.", "contents": "A study of changes in the spine in weight lifters and other athletes. The present study was undertaken in sportsmen of those groups of sports activities where weight training exercises constitute a major part of the training. Two groups consisting of 25 weight-lifters and 25 track and field athletes were studied to find out the effect of sports activities and lifting weights on the spine. 84% weight-lifters and 72% track and field athletes suffered from varying abnormalities. Incidence of backache in 25 weight-lifters was 40% and in 25 track and field athletes 48%. Radiological changes were more common in weight-lifters (84%) than in athletes (72%). Reduction in lumbar lordosis was found in three cases (12%) in both the groups. Obtuse angle deformity of vertebral margins was found in 11 cases (44%) amongst weight-lifters and six cases (24%) amongst athletes. Osteophytic formation was found in six cases (24%) in weight-lifters and four cases (16%) in athletes. Schmorl's node were noticed in five cases (20%) amongst weight-lifters and seven cases (28%) amongst athletes. The incidences of spondylosis and Schmorl's node were found only in those cases who had been doing weight training exercises for more than four years."} {"id": "PMID:157180", "title": "A comparison of xenon-133 clearance with electromagnetic flowmeters and an indicator dilution method for the measurement of liver blood flow.", "content": "Measurement of liver blood flow has been carried out by three different methods in 14 dogs to assess the accuracy of xenon-133 clearance following portal vein injection. Electromagnetic flowmetry with flow probes on the hepatic artery and portal vein resulted in a mean value of 121.9 +/- 39.3 ml min-1 100 g-1. An indicator dilution study utilizing chromium-51-labelled red cells gave a mean value of 119.4 +/- 31.4 ml min-1 100 g-1 and the xenon-133 clearance following portal vein injection, 120.3 +/- 33.8 ml min-1 100 g-1. One-way analysis of variance showed no statistically significant variation between these three groups. There was a close correlation between xenon-133 clearance and electromagnetic flowmetry and between xenon-133 clearance and the indicator dilution technique. These data suggest that xenon-133 clearance following portal vein injection gives an accurate assessment of liver blood flow and this technique (as well as direct parenchymal injection) can be adapted for clinical use.", "contents": "A comparison of xenon-133 clearance with electromagnetic flowmeters and an indicator dilution method for the measurement of liver blood flow. Measurement of liver blood flow has been carried out by three different methods in 14 dogs to assess the accuracy of xenon-133 clearance following portal vein injection. Electromagnetic flowmetry with flow probes on the hepatic artery and portal vein resulted in a mean value of 121.9 +/- 39.3 ml min-1 100 g-1. An indicator dilution study utilizing chromium-51-labelled red cells gave a mean value of 119.4 +/- 31.4 ml min-1 100 g-1 and the xenon-133 clearance following portal vein injection, 120.3 +/- 33.8 ml min-1 100 g-1. One-way analysis of variance showed no statistically significant variation between these three groups. There was a close correlation between xenon-133 clearance and electromagnetic flowmetry and between xenon-133 clearance and the indicator dilution technique. These data suggest that xenon-133 clearance following portal vein injection gives an accurate assessment of liver blood flow and this technique (as well as direct parenchymal injection) can be adapted for clinical use."} {"id": "PMID:157181", "title": "Sparks mandril, velour Dacron and autogenous saphenous vein grafts in femoropopliteal bypass.", "content": "Ninety-nine consecutive vascular reconstructions with femoropopliteal bypass performed during 1973--6 have been reviewed. A Sparks mandril was used in 11 patients, reversed autogenous saphenous vein in 30 and velour Dacron prostheses in 58. The indication for operation was severe ischaemia in 79 per cent. The overall patency rate at 12 months was 70 per cent for autogenous vein, 46 per cent for velour Dacron prosthesis and 18 per cent for Sparks mandril. When the distal anastomosis was located above the knee the patency rate was 100 per cent and 87 per cent for autogenous vein and velour Dacron graft respectively, while the corresponding figures for distal anastomosis below the knee were 58 per cent and 11 per cent. At follow-up 60 per cent of the patients showed improvement owing to the vascular reconstruction.", "contents": "Sparks mandril, velour Dacron and autogenous saphenous vein grafts in femoropopliteal bypass. Ninety-nine consecutive vascular reconstructions with femoropopliteal bypass performed during 1973--6 have been reviewed. A Sparks mandril was used in 11 patients, reversed autogenous saphenous vein in 30 and velour Dacron prostheses in 58. The indication for operation was severe ischaemia in 79 per cent. The overall patency rate at 12 months was 70 per cent for autogenous vein, 46 per cent for velour Dacron prosthesis and 18 per cent for Sparks mandril. When the distal anastomosis was located above the knee the patency rate was 100 per cent and 87 per cent for autogenous vein and velour Dacron graft respectively, while the corresponding figures for distal anastomosis below the knee were 58 per cent and 11 per cent. At follow-up 60 per cent of the patients showed improvement owing to the vascular reconstruction."} {"id": "PMID:157184", "title": "Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry.", "content": "The possibility of using in vivo voltammetry to monitor 5-hydroxytryptamine (5-HT) release from brain tissue in freely moving unanaesthetized rats has been examined. A potential (+0.2 to +1.0 V) was applied to a micrographite electrode stereotaxically placed within a specific brain region and current changes following the oxidation of electroactive compounds in the vicinity of the electrode tip were recorded. Administration of p-chloroamphetamine (5 mg/kg) produced a large increase in current in the striatum and this could be prevented by pretreatment with p-chlorophenylalanine (150 mg/kg X 2) to deplete brain 5-HT or Fluoxetine (10 mg/kg) which prevents the uptake of p-chloroamphetamine by 5-HT neurones. Fluoxetine (10 mg/kg) caused a small but long lasting increase in current. Stimulation of the median raphe nucleus produced a marked and rapid rise in current in the hippocampus but a much smaller one in the striatum. This response could also be prevented by 24 h pretreatment with p-chlorophenylalanine (150 mg/kg). Seven days after p-chlorophenylalanine administration raphe stimulation again produced an increase in current. Rats under barbiturate anaesthesia showed no clear increase in current either after p-chloroamphetamine or raphe stimulation, indicating that barbiturates may affect neurotransmitter release. The results suggest that 5-HT release can be monitored in the freely moving unanaesthetized rat using in vivo voltammetry, and that a moderate decrease in brain 5-HT concentration leads to a substantial inhibition of drug or stimulation induced release of 5-HT.", "contents": "Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry. The possibility of using in vivo voltammetry to monitor 5-hydroxytryptamine (5-HT) release from brain tissue in freely moving unanaesthetized rats has been examined. A potential (+0.2 to +1.0 V) was applied to a micrographite electrode stereotaxically placed within a specific brain region and current changes following the oxidation of electroactive compounds in the vicinity of the electrode tip were recorded. Administration of p-chloroamphetamine (5 mg/kg) produced a large increase in current in the striatum and this could be prevented by pretreatment with p-chlorophenylalanine (150 mg/kg X 2) to deplete brain 5-HT or Fluoxetine (10 mg/kg) which prevents the uptake of p-chloroamphetamine by 5-HT neurones. Fluoxetine (10 mg/kg) caused a small but long lasting increase in current. Stimulation of the median raphe nucleus produced a marked and rapid rise in current in the hippocampus but a much smaller one in the striatum. This response could also be prevented by 24 h pretreatment with p-chlorophenylalanine (150 mg/kg). Seven days after p-chlorophenylalanine administration raphe stimulation again produced an increase in current. Rats under barbiturate anaesthesia showed no clear increase in current either after p-chloroamphetamine or raphe stimulation, indicating that barbiturates may affect neurotransmitter release. The results suggest that 5-HT release can be monitored in the freely moving unanaesthetized rat using in vivo voltammetry, and that a moderate decrease in brain 5-HT concentration leads to a substantial inhibition of drug or stimulation induced release of 5-HT."} {"id": "PMID:157186", "title": "[Blood pressure and mesenteric blood flow in rats during the infusion of biogenic amines. Effect of supralethal irradiation].", "content": "The action of biogenic amines (noradrenaline, dopamine), infused at different concentration into the aorta of the urethane anesthetized control and irradiated rats for 2 min., was followed on the basis of systemic blood pressure and mesenteric blood flow. The mesenteric blood flow was measured by means of an electromagnetic flow meter. The changes observed i.e. after dopamine an increase in pressure and flow, after noradrenaline an increase in pressure and a decrease in flow with an increase after infusion had been stopped, correspond to those obtained in larger animals. In many, but not in all cases, the response is proportional to the log of the concentration of the amine infused. Irradiation with 2 kR, i.e. a dose which causes the animals to die from the gastrointestinal syndrome after 3 days, modified the response to dopamine and noradrenaline. The changes are, for noradrenaline, a greater pressure and a lower flow responses and for dopamine a greater pressure response at low and middle doses.", "contents": "[Blood pressure and mesenteric blood flow in rats during the infusion of biogenic amines. Effect of supralethal irradiation]. The action of biogenic amines (noradrenaline, dopamine), infused at different concentration into the aorta of the urethane anesthetized control and irradiated rats for 2 min., was followed on the basis of systemic blood pressure and mesenteric blood flow. The mesenteric blood flow was measured by means of an electromagnetic flow meter. The changes observed i.e. after dopamine an increase in pressure and flow, after noradrenaline an increase in pressure and a decrease in flow with an increase after infusion had been stopped, correspond to those obtained in larger animals. In many, but not in all cases, the response is proportional to the log of the concentration of the amine infused. Irradiation with 2 kR, i.e. a dose which causes the animals to die from the gastrointestinal syndrome after 3 days, modified the response to dopamine and noradrenaline. The changes are, for noradrenaline, a greater pressure and a lower flow responses and for dopamine a greater pressure response at low and middle doses."} {"id": "PMID:157187", "title": "[Immediate effects of desoxycorticosterone of vasomotor properties of noradrenaline and isoprenaline in rats].", "content": "In the rat, desoxycorticosterone (3 to 10 mg p. kg) does not modify the systemic vasoconstriction provoked by noradrenaline even in presence of an excess of sodium chloride. This mineralo-steroid reduces the vasodilatation induced by isoprenaline. Sodium chloride in excess potentiates this inhibition.", "contents": "[Immediate effects of desoxycorticosterone of vasomotor properties of noradrenaline and isoprenaline in rats]. In the rat, desoxycorticosterone (3 to 10 mg p. kg) does not modify the systemic vasoconstriction provoked by noradrenaline even in presence of an excess of sodium chloride. This mineralo-steroid reduces the vasodilatation induced by isoprenaline. Sodium chloride in excess potentiates this inhibition."} {"id": "PMID:157188", "title": "[Proprioceptive feedback and temporal regulation in cats].", "content": "Temporal regulation in cats was studied using operant conditioning techniques; milk was delivered according to either a two-lever response duration schedule or a two-lever DRL schedule. After an equal number of experimental sessions, the subjects on the DRL schedule reached larger delay values than the subjects on the response duration schedule. Hypotheses concerning the intervention of proprioceptive feedback in the temporal regulation of motor behavior are discussed.", "contents": "[Proprioceptive feedback and temporal regulation in cats]. Temporal regulation in cats was studied using operant conditioning techniques; milk was delivered according to either a two-lever response duration schedule or a two-lever DRL schedule. After an equal number of experimental sessions, the subjects on the DRL schedule reached larger delay values than the subjects on the response duration schedule. Hypotheses concerning the intervention of proprioceptive feedback in the temporal regulation of motor behavior are discussed."} {"id": "PMID:157189", "title": "[Relationship between lipemia and sensitivity to arachidonic acid in rabbits].", "content": "The hypotensive effect of arachidonic acid in the rabbit increases simultaneously with the fall of the plasmatic unesterified fatty acids (NEFA), after treatment with nicotinic acid or heparin. In the case of nicotinic acid sensitization, which occurs in 10 minutes, the fall of NEFA occurs immediately. The sensitization by heparin appears only after 40 minutes following the injection; during this latency, the NEFA are enhanced; after the fall of NEFA, the rabbit becomes more sensitive to arachidonic acid. Mechanisms of heparinic sensitization are discussed.", "contents": "[Relationship between lipemia and sensitivity to arachidonic acid in rabbits]. The hypotensive effect of arachidonic acid in the rabbit increases simultaneously with the fall of the plasmatic unesterified fatty acids (NEFA), after treatment with nicotinic acid or heparin. In the case of nicotinic acid sensitization, which occurs in 10 minutes, the fall of NEFA occurs immediately. The sensitization by heparin appears only after 40 minutes following the injection; during this latency, the NEFA are enhanced; after the fall of NEFA, the rabbit becomes more sensitive to arachidonic acid. Mechanisms of heparinic sensitization are discussed."} {"id": "PMID:157185", "title": "Effects of midbrain raphe lesions or systemic p-chlorophenylalanine on the development of kindled seizures in rats.", "content": "Previous research has suggested that brain serotonin (5-hydroxytryptamine or 5-HT) neurons inhibit epileptiform seizure activity. To test further this possibility, experiments were performed to determine if brain 5-HT depletion would enhance the occurrence and/or magnitude of seizures \"kindled\" from the amygdala or neocortex of rats. Two modes of 5-HT depletion were used: (1) radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei, and (2) systemic injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (pCPA). Both modes of 5-HT depletion reliably enhanced the strength of motor convulsions kindled from the cortex. Systemic pCPA also reduced the duration of after-discharges (ADs) in cortically-stimulated rats. However, pCPA reduced rather than enhanced convulsions kindled from the amygdala. In contrast to this, raphe lesions appeared to sensitize rats to the effects of amygdaloid kindling, i.e., lesions lowered AD thresholds, AD durations and number of ADs to elicit motor convulsions. Viewed together, these data support the hypothesis that 5-HT neurons can serve to inhibit seizures. However, the lack of robustness across parameters of epileptogenesis as well as discrepant findings related to 5-HT depletion mode additionally suggest that kindled seizures affect other neuronal populations in addition to those under serotonergic influence.", "contents": "Effects of midbrain raphe lesions or systemic p-chlorophenylalanine on the development of kindled seizures in rats. Previous research has suggested that brain serotonin (5-hydroxytryptamine or 5-HT) neurons inhibit epileptiform seizure activity. To test further this possibility, experiments were performed to determine if brain 5-HT depletion would enhance the occurrence and/or magnitude of seizures \"kindled\" from the amygdala or neocortex of rats. Two modes of 5-HT depletion were used: (1) radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei, and (2) systemic injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (pCPA). Both modes of 5-HT depletion reliably enhanced the strength of motor convulsions kindled from the cortex. Systemic pCPA also reduced the duration of after-discharges (ADs) in cortically-stimulated rats. However, pCPA reduced rather than enhanced convulsions kindled from the amygdala. In contrast to this, raphe lesions appeared to sensitize rats to the effects of amygdaloid kindling, i.e., lesions lowered AD thresholds, AD durations and number of ADs to elicit motor convulsions. Viewed together, these data support the hypothesis that 5-HT neurons can serve to inhibit seizures. However, the lack of robustness across parameters of epileptogenesis as well as discrepant findings related to 5-HT depletion mode additionally suggest that kindled seizures affect other neuronal populations in addition to those under serotonergic influence."} {"id": "PMID:157190", "title": "[Hypotensive action of arachidonic acid, slow acting analphylactic substance (SRS-A) and thromboxane A2 in rats].", "content": "In the rat, diethylcarbamazine, imidazole and L 8027 do not modify the hypotensive activity of PGE2 and arachidonic acid. The formation of SRS-A from arachidonic acid does not compete with the synthesis of PG in the cardiovascular system of the rat. The thromboxane A2 does not participate in the hypotensive activity of arachidonic acid in the rat.", "contents": "[Hypotensive action of arachidonic acid, slow acting analphylactic substance (SRS-A) and thromboxane A2 in rats]. In the rat, diethylcarbamazine, imidazole and L 8027 do not modify the hypotensive activity of PGE2 and arachidonic acid. The formation of SRS-A from arachidonic acid does not compete with the synthesis of PG in the cardiovascular system of the rat. The thromboxane A2 does not participate in the hypotensive activity of arachidonic acid in the rat."} {"id": "PMID:157191", "title": "[Effect of age on the sensitivity of mouse spermatogonia to mutagenic action].", "content": "Male BALB/c mice were whole body exposed to 0, 100, 200 or 300 R of X-rays or were given an i.p. injection of 5 mg/kg of thio-TEPA at 3 months or at 12 months of age. One hundred days after treatment the testes were examined for the presence of reciprocal translocations induced in spermatogonia and detectable in the dividing spermatocytes. Our results show that ages does not influence the yield of scorable chromosome rearrangements.", "contents": "[Effect of age on the sensitivity of mouse spermatogonia to mutagenic action]. Male BALB/c mice were whole body exposed to 0, 100, 200 or 300 R of X-rays or were given an i.p. injection of 5 mg/kg of thio-TEPA at 3 months or at 12 months of age. One hundred days after treatment the testes were examined for the presence of reciprocal translocations induced in spermatogonia and detectable in the dividing spermatocytes. Our results show that ages does not influence the yield of scorable chromosome rearrangements."} {"id": "PMID:157192", "title": "[Transport of metanephrine in vitro in rat renal cortex].", "content": "In vitro, accumulation of metanephrine is described in renal cortex of the rat (tissue/medium ratio greater than 5). This accumulation is saturable and energy dependent.", "contents": "[Transport of metanephrine in vitro in rat renal cortex]. In vitro, accumulation of metanephrine is described in renal cortex of the rat (tissue/medium ratio greater than 5). This accumulation is saturable and energy dependent."} {"id": "PMID:157193", "title": "[Effect of exogenous progesterone and estradiol on the process of embryonic implantation in lead intoxicated female mice].", "content": "Exposure of female mice to high doses of lead from the first day of pregnancy inhibits embryonic implantation. Animals exposed to 0.5% of lead in diet received injections of progesterone and estradiol, from day 4 to day 7 or from day 5 to day 8 of pregnancy. Such treatments induced implantation in respectively 50 and 80% of the mice. In controls, implantation was observed in 60% of the animals. In animals exposed to lead but not hormone-treated, no implantation was observed. The inhibition of implantation caused by lead seems thus to be due mainly to an action of this metal on the hormonal balance of the exposed mother, and this confirms our earlier results.", "contents": "[Effect of exogenous progesterone and estradiol on the process of embryonic implantation in lead intoxicated female mice]. Exposure of female mice to high doses of lead from the first day of pregnancy inhibits embryonic implantation. Animals exposed to 0.5% of lead in diet received injections of progesterone and estradiol, from day 4 to day 7 or from day 5 to day 8 of pregnancy. Such treatments induced implantation in respectively 50 and 80% of the mice. In controls, implantation was observed in 60% of the animals. In animals exposed to lead but not hormone-treated, no implantation was observed. The inhibition of implantation caused by lead seems thus to be due mainly to an action of this metal on the hormonal balance of the exposed mother, and this confirms our earlier results."} {"id": "PMID:157194", "title": "[Lead toxicity in mice embryos].", "content": "Administration to female mice before co\u00eftus and to pregnant female mice of an alimentation containing 0.1 p. 100 lead acetate imparied the fertility. Studies on the changes of the ultrastructure of the embryos during the first stages of development do not allow to detect lesions unless on day 7 where lead inclusions are detected in the mitochondria.", "contents": "[Lead toxicity in mice embryos]. Administration to female mice before co\u00eftus and to pregnant female mice of an alimentation containing 0.1 p. 100 lead acetate imparied the fertility. Studies on the changes of the ultrastructure of the embryos during the first stages of development do not allow to detect lesions unless on day 7 where lead inclusions are detected in the mitochondria."} {"id": "PMID:157196", "title": "[Inhibition of mammary carcinogenesis of C3H/f mice with broparestrol].", "content": "Administration of bromotriphenylethylene to C3H/f female mice implanted with a pituitary under the kidney capsule produce an inhibition of mammary carcinogenesis with high doses (20 ppm or 200 ppm in the diet). With a diet containing 2 ppm no inhibition is observed.", "contents": "[Inhibition of mammary carcinogenesis of C3H/f mice with broparestrol]. Administration of bromotriphenylethylene to C3H/f female mice implanted with a pituitary under the kidney capsule produce an inhibition of mammary carcinogenesis with high doses (20 ppm or 200 ppm in the diet). With a diet containing 2 ppm no inhibition is observed."} {"id": "PMID:157197", "title": "[Comparison of the sweating rate under thermal constraint equivalent at rest and during exercise].", "content": "Subjects exposed to tolerable thermal constraints of equal intensity at rest and during exercise start sweating at lower mean body temperatures during exercise and the sweating rate increases faster during exercise than at rest.", "contents": "[Comparison of the sweating rate under thermal constraint equivalent at rest and during exercise]. Subjects exposed to tolerable thermal constraints of equal intensity at rest and during exercise start sweating at lower mean body temperatures during exercise and the sweating rate increases faster during exercise than at rest."} {"id": "PMID:157198", "title": "[Kinetic properties of an alkaline phosphatase from honeybee intestine determined by a new rigorous algebraic method].", "content": "The Hill-parameters : max. velocity (VM), affinity constant (K) and resultant reaction order (n) of an alk. phosphatase (Mol. Weight 100 to 130,000) from guts of foraging worker-bees, have been calculated according to new algebraic equations allowing a rigorous determination without any extrapolation. The parameters determined from 2 strains of the same race, at 3 years interval, do not differ, and the Hill coefficients (n) are significantly lower than 1, namely : n = 0.621 +/- 0.014 (3 detn.) and n = 0,600 +/- 0,016 (t detn.) which suggest the hypothesis of a negative cooperative mechanism.", "contents": "[Kinetic properties of an alkaline phosphatase from honeybee intestine determined by a new rigorous algebraic method]. The Hill-parameters : max. velocity (VM), affinity constant (K) and resultant reaction order (n) of an alk. phosphatase (Mol. Weight 100 to 130,000) from guts of foraging worker-bees, have been calculated according to new algebraic equations allowing a rigorous determination without any extrapolation. The parameters determined from 2 strains of the same race, at 3 years interval, do not differ, and the Hill coefficients (n) are significantly lower than 1, namely : n = 0.621 +/- 0.014 (3 detn.) and n = 0,600 +/- 0,016 (t detn.) which suggest the hypothesis of a negative cooperative mechanism."} {"id": "PMID:157199", "title": "[Effect of thyrocalcitonin and an alpha blocking agent in the secretion of amylase, in vitro, on rat parotid and pancreas].", "content": "Porcine Calcitonin, together with an alpha adrenergic blocking agent, stimulates amylase release from rat parotid or pancreas, in vitro. A beta blocking agent, propranolol, inhibits this effect. In pancreas only, the coupling of stimulus by calcitonin and phenoxybenzamine involves calcium control.", "contents": "[Effect of thyrocalcitonin and an alpha blocking agent in the secretion of amylase, in vitro, on rat parotid and pancreas]. Porcine Calcitonin, together with an alpha adrenergic blocking agent, stimulates amylase release from rat parotid or pancreas, in vitro. A beta blocking agent, propranolol, inhibits this effect. In pancreas only, the coupling of stimulus by calcitonin and phenoxybenzamine involves calcium control."} {"id": "PMID:157200", "title": "[Effect of haemolysin of Pseudomonas aeruginosa on Ehrlich ascites tumor cells].", "content": "Haemolysin of Pseudomonas aeruginosa exerts toxic effects upon the metabolism of Ehrlich ascitic tumor cells : morphological changes appear readily ; respiration is inhibited more slowly ; the lethal effect determined by intraperitoneal injection of tumor cells is neutralized. Inhibition with human normal sera is complete for the hemolytic action, but incomplete for the cytopathic action.", "contents": "[Effect of haemolysin of Pseudomonas aeruginosa on Ehrlich ascites tumor cells]. Haemolysin of Pseudomonas aeruginosa exerts toxic effects upon the metabolism of Ehrlich ascitic tumor cells : morphological changes appear readily ; respiration is inhibited more slowly ; the lethal effect determined by intraperitoneal injection of tumor cells is neutralized. Inhibition with human normal sera is complete for the hemolytic action, but incomplete for the cytopathic action."} {"id": "PMID:157201", "title": "[Effect of porcine calcitonin on human blood platelet aggregation in vitro].", "content": "Porcine calcitonin used in vitro increases ADP and collagene induced aggregation in human platelets.", "contents": "[Effect of porcine calcitonin on human blood platelet aggregation in vitro]. Porcine calcitonin used in vitro increases ADP and collagene induced aggregation in human platelets."} {"id": "PMID:157202", "title": "[Organ culture of human skin using dermis from cadavers].", "content": "An original method for organ culture of human skin epithelial cells using as a support human skin grafts obtained from the Human tissue Band of \"C.H.R. de Bordeaux\" is described. Methods and results of this technic which seems to represent a forward step relative to traditional practices are exposed.", "contents": "[Organ culture of human skin using dermis from cadavers]. An original method for organ culture of human skin epithelial cells using as a support human skin grafts obtained from the Human tissue Band of \"C.H.R. de Bordeaux\" is described. Methods and results of this technic which seems to represent a forward step relative to traditional practices are exposed."} {"id": "PMID:157203", "title": "[Nycthemeral variations of blood and urine urea, creatinine and total proteins in rats].", "content": "The present study evidences blood and urine urea, creatinine and total proteins circadian variations in 50 male rats. Venous blood is sampled at behind socket sinus once a week at different hours (8, 11, 14, 17, 20, 23, 2 and 5) and urines are collected during 4 consecutive six hours periods in animals living in metabolism cages (8-14, 14-20, 20-2, 2-8). Blood three nitrogen substances circadian variations bring out the decrease at 17 h and increase at 23 or 2 h. Urinary excretion variations curves shows, in all cases, an increase more than 40% during the nightly periods. The influence of feeding rhythms on the blood and urine three derivates circadian rhythms is discussed. Moreover, night diuresis increase and urea and creatinine urinary remarkable constancy suggest water, solutes and macrosolutes transglomerular pathway nightly increase existence. Urea (+ 40%) and creatinine (+ 30%) clearance nightly significative increase confirms glomerular filtration circadian variations and its nightly increase.", "contents": "[Nycthemeral variations of blood and urine urea, creatinine and total proteins in rats]. The present study evidences blood and urine urea, creatinine and total proteins circadian variations in 50 male rats. Venous blood is sampled at behind socket sinus once a week at different hours (8, 11, 14, 17, 20, 23, 2 and 5) and urines are collected during 4 consecutive six hours periods in animals living in metabolism cages (8-14, 14-20, 20-2, 2-8). Blood three nitrogen substances circadian variations bring out the decrease at 17 h and increase at 23 or 2 h. Urinary excretion variations curves shows, in all cases, an increase more than 40% during the nightly periods. The influence of feeding rhythms on the blood and urine three derivates circadian rhythms is discussed. Moreover, night diuresis increase and urea and creatinine urinary remarkable constancy suggest water, solutes and macrosolutes transglomerular pathway nightly increase existence. Urea (+ 40%) and creatinine (+ 30%) clearance nightly significative increase confirms glomerular filtration circadian variations and its nightly increase."} {"id": "PMID:157204", "title": "[Effect of Bacillus Callmette Guerin (BCG) on the receptivity of nude mice to Schistosoma mansoni].", "content": "\"Nude\" mice are injected intravenously with 1 mg live BCG each. Pulmonary schistosomules, counted 5 days after infestation with Schistosoma mansoni cercaria are observed to be fewer in injected mice than in non-injected controls. This show that BCG immunostamulation can be obtained when mature T lymphocytes are absent.", "contents": "[Effect of Bacillus Callmette Guerin (BCG) on the receptivity of nude mice to Schistosoma mansoni]. \"Nude\" mice are injected intravenously with 1 mg live BCG each. Pulmonary schistosomules, counted 5 days after infestation with Schistosoma mansoni cercaria are observed to be fewer in injected mice than in non-injected controls. This show that BCG immunostamulation can be obtained when mature T lymphocytes are absent."} {"id": "PMID:157205", "title": "[Correlation of structural and ultrastructural modifications of the renal cortex with water, sodium and protein excretion in rats rendered hypertensive by perinephritic constriction by collodion].", "content": "Water, sodium and proteins renal excretion in with collodion Page's method hypertensive rats is compared with that of same Wistar strained control rats. Blood pressure of treated animals (n = 16) is 193.1 Hg mm (138 in control rats). Urinary flow increases from 19.5 to 33.7 ml/24 h (+ 72.8%), sodium excretion from 29.6 to 37.5 mg/24 h (+ 26.7%) and total proteins excretion from 23.5 to 63 mg/24 h (+ 169%. This data are correlated with the renal cortex morphological changes with photon and electron microscope. Severe damages are seen in Bowman's capsule and in glomerular copruscules, especially at the epithelial layer level. Important proteic pools occur within tubular lumen. Proximal tubular epithelium seems normal. On the other hand, distal tubular epithelium seriously scales. So, important water, sodium and proteins excretion increase in our experimental hypertension model can be explained. It is also discussed about functional and structural modifications analogy in our model's rats and in spontaneously hypertensive rats (SHB).", "contents": "[Correlation of structural and ultrastructural modifications of the renal cortex with water, sodium and protein excretion in rats rendered hypertensive by perinephritic constriction by collodion]. Water, sodium and proteins renal excretion in with collodion Page's method hypertensive rats is compared with that of same Wistar strained control rats. Blood pressure of treated animals (n = 16) is 193.1 Hg mm (138 in control rats). Urinary flow increases from 19.5 to 33.7 ml/24 h (+ 72.8%), sodium excretion from 29.6 to 37.5 mg/24 h (+ 26.7%) and total proteins excretion from 23.5 to 63 mg/24 h (+ 169%. This data are correlated with the renal cortex morphological changes with photon and electron microscope. Severe damages are seen in Bowman's capsule and in glomerular copruscules, especially at the epithelial layer level. Important proteic pools occur within tubular lumen. Proximal tubular epithelium seems normal. On the other hand, distal tubular epithelium seriously scales. So, important water, sodium and proteins excretion increase in our experimental hypertension model can be explained. It is also discussed about functional and structural modifications analogy in our model's rats and in spontaneously hypertensive rats (SHB)."} {"id": "PMID:157206", "title": "[Development of seminiferous tubules in guinea pigs during puberty].", "content": "The study of development of the seminiferous tubules of the guinea-pig along the puberty is based on diameter, length and volume relate to testicular weight and age. During this period the development is linear. A correlation exist between testicular testosterone concentration and growth of seminiferous tubules in diameter and in length from day 16 to 60, stage of puberty in which the first spermatozoa appear.", "contents": "[Development of seminiferous tubules in guinea pigs during puberty]. The study of development of the seminiferous tubules of the guinea-pig along the puberty is based on diameter, length and volume relate to testicular weight and age. During this period the development is linear. A correlation exist between testicular testosterone concentration and growth of seminiferous tubules in diameter and in length from day 16 to 60, stage of puberty in which the first spermatozoa appear."} {"id": "PMID:157207", "title": "[Chronic vascular catheterization in the rat. Adaptation to injections and semi-continous blood sampling for hormonal studies].", "content": "A method for frequent sampling of blood and injections of fluids in undisturbed rats is described. The right external jugular vein and the left carotid artery are cannulated without completely blood stream interruption in the vessel. Injection or perfusion can be performed during several weeks. Blood was collected for at least 15 post-operative days. The technique appears suitable for pituitary kinetics studies which can be carried out several times in rats bearing indwelling catheters.", "contents": "[Chronic vascular catheterization in the rat. Adaptation to injections and semi-continous blood sampling for hormonal studies]. A method for frequent sampling of blood and injections of fluids in undisturbed rats is described. The right external jugular vein and the left carotid artery are cannulated without completely blood stream interruption in the vessel. Injection or perfusion can be performed during several weeks. Blood was collected for at least 15 post-operative days. The technique appears suitable for pituitary kinetics studies which can be carried out several times in rats bearing indwelling catheters."} {"id": "PMID:157208", "title": "[Effect of dietary protein levels on the amount of blood free amino acids in lambs].", "content": "Growing lambs were fed increasing amounts of nitrogenous matter (12 to 20 per 100 on dry matter basis). Free amino acid and urea levels were measured in blood of 37 kg lambs. When crude protein content of diets exceeded 16 per 100, the catabolism of several essential amino acids increased. Methionine, lysine and histidine seemed to be limiting for growing lambs.", "contents": "[Effect of dietary protein levels on the amount of blood free amino acids in lambs]. Growing lambs were fed increasing amounts of nitrogenous matter (12 to 20 per 100 on dry matter basis). Free amino acid and urea levels were measured in blood of 37 kg lambs. When crude protein content of diets exceeded 16 per 100, the catabolism of several essential amino acids increased. Methionine, lysine and histidine seemed to be limiting for growing lambs."} {"id": "PMID:157209", "title": "[Modification of neurosecretory cells in the preoptic nucleus of tench (Tinca tinca) and of various plasm ions following an elevation of water temperature].", "content": "Temperature increasing in water is responsible in Tench of on activity decrease in neurosecretory cells of preoptic nucleus, and of an increase in sodium plasmatic concentration. Influence of parameter is discussed.", "contents": "[Modification of neurosecretory cells in the preoptic nucleus of tench (Tinca tinca) and of various plasm ions following an elevation of water temperature]. Temperature increasing in water is responsible in Tench of on activity decrease in neurosecretory cells of preoptic nucleus, and of an increase in sodium plasmatic concentration. Influence of parameter is discussed."} {"id": "PMID:157210", "title": "[Chronic ethanol intoxication in mice by the pulmonary route. Its use in the study of tryptophan penetration into the brain].", "content": "Pulmonary ethanol absorption produces homogeneous intoxicated mices within a week. Intoxication is evidenced in the increase of plasmatic, hepatic and cerebral gamma-glutamyl-transferases. An increase of blood-brain-barrier permeability for tryptophan is not observed as in acute intoxication.", "contents": "[Chronic ethanol intoxication in mice by the pulmonary route. Its use in the study of tryptophan penetration into the brain]. Pulmonary ethanol absorption produces homogeneous intoxicated mices within a week. Intoxication is evidenced in the increase of plasmatic, hepatic and cerebral gamma-glutamyl-transferases. An increase of blood-brain-barrier permeability for tryptophan is not observed as in acute intoxication."} {"id": "PMID:157211", "title": "[Post-natal development of hematocrit in calves].", "content": "This study was carried out on 470 veal calves fed only with milk. Calves with haematocrit value before slaughter higher than 39.0, from 32.5 to 34.5 and lower than 25.0 has red, pink or white meat. Comparison between haematocrit of newborn and 3 months old calves showed two separate situations : decrease of haematocrit for values at birth higher than 38.9 and increase for values lower than 32.3.", "contents": "[Post-natal development of hematocrit in calves]. This study was carried out on 470 veal calves fed only with milk. Calves with haematocrit value before slaughter higher than 39.0, from 32.5 to 34.5 and lower than 25.0 has red, pink or white meat. Comparison between haematocrit of newborn and 3 months old calves showed two separate situations : decrease of haematocrit for values at birth higher than 38.9 and increase for values lower than 32.3."} {"id": "PMID:157212", "title": "[Lethargic hypothermia induced by a protein free diet in a hibernating rodent, the dormouse (Eliomys quercinus L.)].", "content": "In garden dormouse protein deficiency leads to reversible hypothermic torpor, comparable with that provoked by starvation or occuring naturally during hibernation, whether the diet consists wholly of apples or of synthetic protein-free food. Torpor induced by protein deficiency occurs even though the energy requirements of the animal are amply satisfied. These phases of lethargy occur after a certain delay and with a variable frequency, both of which vary with the ambient temperature.", "contents": "[Lethargic hypothermia induced by a protein free diet in a hibernating rodent, the dormouse (Eliomys quercinus L.)]. In garden dormouse protein deficiency leads to reversible hypothermic torpor, comparable with that provoked by starvation or occuring naturally during hibernation, whether the diet consists wholly of apples or of synthetic protein-free food. Torpor induced by protein deficiency occurs even though the energy requirements of the animal are amply satisfied. These phases of lethargy occur after a certain delay and with a variable frequency, both of which vary with the ambient temperature."} {"id": "PMID:157214", "title": "[Central origin on the excito-motric action of morphine on intestine].", "content": "In ewew fitted with a cerebro-ventricular cannula and equipped with extra-cellular bipolar electrodes on the antrum and proximal small intestine, an intraventricular injection of morphine at a dose (40 micrograms/kg) ineffective peripherally was followed within 1 min by an increased spike activity of the duodenum without disruption of the occurrence of migrating myoelectric complexes. This effect was paralleled by a reduction of antral motility and abolished by small intraventricular doses of nalorphine. After an intravenous injection of large doses of the drug drug (0.8 mg/kg), spike activity was increased at both jejunal and duodenal level without changes in the antrum and followed by a long-lasting disorganization of the motor profile. The results suggested a centrally mediated gastro-duodenal effect of morphine.", "contents": "[Central origin on the excito-motric action of morphine on intestine]. In ewew fitted with a cerebro-ventricular cannula and equipped with extra-cellular bipolar electrodes on the antrum and proximal small intestine, an intraventricular injection of morphine at a dose (40 micrograms/kg) ineffective peripherally was followed within 1 min by an increased spike activity of the duodenum without disruption of the occurrence of migrating myoelectric complexes. This effect was paralleled by a reduction of antral motility and abolished by small intraventricular doses of nalorphine. After an intravenous injection of large doses of the drug drug (0.8 mg/kg), spike activity was increased at both jejunal and duodenal level without changes in the antrum and followed by a long-lasting disorganization of the motor profile. The results suggested a centrally mediated gastro-duodenal effect of morphine."} {"id": "PMID:157215", "title": "[Effects of chlorpromazine on hypertension by desinhibition in dogs: comparison of intravenous and intracisternal administration].", "content": "The tensional effects of intravenous and intracisternal chlorpromazine were studied in neurogenic hypertensive dogs by desinhibition and bilateral vagotomy. Intravenous (2-5 mg/kg) chlorpromazine corrected instantaneously the rise in blood pressure after desinhibition, but was inactive on tachycardia. Intracisternal (0.5-2 mg/kg) chlorpromazine was always inactive in the desinhibited dog. These results exclude an intervention from baro -- or chemo -- receptors and central sympathetic structures (alpha adrenergic or dopaminergic receptors). They show that the hypotensive effect of chlorpromazine is a peripheral mechanism.", "contents": "[Effects of chlorpromazine on hypertension by desinhibition in dogs: comparison of intravenous and intracisternal administration]. The tensional effects of intravenous and intracisternal chlorpromazine were studied in neurogenic hypertensive dogs by desinhibition and bilateral vagotomy. Intravenous (2-5 mg/kg) chlorpromazine corrected instantaneously the rise in blood pressure after desinhibition, but was inactive on tachycardia. Intracisternal (0.5-2 mg/kg) chlorpromazine was always inactive in the desinhibited dog. These results exclude an intervention from baro -- or chemo -- receptors and central sympathetic structures (alpha adrenergic or dopaminergic receptors). They show that the hypotensive effect of chlorpromazine is a peripheral mechanism."} {"id": "PMID:157216", "title": "[Development of equilibrium of glial populations in the cerebral cortex of lead intoxicated rats].", "content": "The three types of glial cells (astrocytes, oligodendrocytes and microglia) were counted at 2 different ages in normal and lead intoxicated animals (on a 0.5% Pb2+ diet) and were found to vary differently with respect to age and lead treatment. Satellisation of nerve cells by glia also displays a different pattern : whereas usually at 3 month age, the neurons are surrounded by oligodendrocytes, they appear more often encapsulated by microglia after lead treatment. It is postulated that changes in glial populations and their relationship to nerve cells could provide a sensitive indicator of lead encephalopathy.", "contents": "[Development of equilibrium of glial populations in the cerebral cortex of lead intoxicated rats]. The three types of glial cells (astrocytes, oligodendrocytes and microglia) were counted at 2 different ages in normal and lead intoxicated animals (on a 0.5% Pb2+ diet) and were found to vary differently with respect to age and lead treatment. Satellisation of nerve cells by glia also displays a different pattern : whereas usually at 3 month age, the neurons are surrounded by oligodendrocytes, they appear more often encapsulated by microglia after lead treatment. It is postulated that changes in glial populations and their relationship to nerve cells could provide a sensitive indicator of lead encephalopathy."} {"id": "PMID:157217", "title": "Calcium binding in cardiac sarcolemma.", "content": "The relationship between calcium binding and ATPase activity has been investigated for guinea pig cardiac sarcolemma. The concentrations of calcium ions and of ATP were the main factors in determining the amount of calcium bound. With a saturating concentration of ATP, at low calcium concentrations (0.1 mM) more than 50% of the total calcium bound was ATP dependent while at high concentrations of calcium (10 mM) only 20% of the calcium bound was ATP dependent. The ATP-dependent calcium binding process involves one class of calcium binding sites while the non-ATP-dependent calcium binding process involves two classes of binding sites. Inhibitor studies of Ca2+-stimulated MgATPase, MgATPase, and CaATPase activities suggest Ca2+ and Mg2+ are either interacting with different sites on the same enzyme or with different enzymes.", "contents": "Calcium binding in cardiac sarcolemma. The relationship between calcium binding and ATPase activity has been investigated for guinea pig cardiac sarcolemma. The concentrations of calcium ions and of ATP were the main factors in determining the amount of calcium bound. With a saturating concentration of ATP, at low calcium concentrations (0.1 mM) more than 50% of the total calcium bound was ATP dependent while at high concentrations of calcium (10 mM) only 20% of the calcium bound was ATP dependent. The ATP-dependent calcium binding process involves one class of calcium binding sites while the non-ATP-dependent calcium binding process involves two classes of binding sites. Inhibitor studies of Ca2+-stimulated MgATPase, MgATPase, and CaATPase activities suggest Ca2+ and Mg2+ are either interacting with different sites on the same enzyme or with different enzymes."} {"id": "PMID:157223", "title": "Ultrastructure and ATPase activity of the rectal gland of the chondrichthyean fish Hydrolagus colliei (Holocephali).", "content": "The anatomy, histology, ultrastructure and ATPase activity of the intramural rectal gland of the chondrichthyean Hydrolagus colliei, are described. The cells of the rectal gland of Hydrolagus demonstrate the same well developed lateral and basal cisternae, elongate mitochondria and luminal border as those of their elasmobranch counterparts. ATPase activity within the rectal gland of Hydrolagus is as intense as that in a number of elasmobranchs examined in the course of the study. Despite its primitive intramural location the rectal gland of Hydrolagus represents a homolog of the more specialized and better known elasmobranch gland and appears as well suited for cation excretion.", "contents": "Ultrastructure and ATPase activity of the rectal gland of the chondrichthyean fish Hydrolagus colliei (Holocephali). The anatomy, histology, ultrastructure and ATPase activity of the intramural rectal gland of the chondrichthyean Hydrolagus colliei, are described. The cells of the rectal gland of Hydrolagus demonstrate the same well developed lateral and basal cisternae, elongate mitochondria and luminal border as those of their elasmobranch counterparts. ATPase activity within the rectal gland of Hydrolagus is as intense as that in a number of elasmobranchs examined in the course of the study. Despite its primitive intramural location the rectal gland of Hydrolagus represents a homolog of the more specialized and better known elasmobranch gland and appears as well suited for cation excretion."} {"id": "PMID:157232", "title": "[Sleep and monoamines: differential radioautography of central neurons after systematic injection of tritiated 5-hydroxytryptophane (5 HTP 3H) or of dihydroxyphenylalanine (DOPA 3H)].", "content": "In normal cats 90 min. after the intravenous injection of 5 mg/kg of 5 HTP and 3H 5 HTP or DOPA and 3H DOPA a few reactive nerve cell bodies were identified by radioautography. On the contrary, 48 hrs. after p-chlorophenylalanin or subtotal lesion of raphe nuclei, these tracers showed numerous reactive neurons inside or outside the central monoaminergic systems.", "contents": "[Sleep and monoamines: differential radioautography of central neurons after systematic injection of tritiated 5-hydroxytryptophane (5 HTP 3H) or of dihydroxyphenylalanine (DOPA 3H)]. In normal cats 90 min. after the intravenous injection of 5 mg/kg of 5 HTP and 3H 5 HTP or DOPA and 3H DOPA a few reactive nerve cell bodies were identified by radioautography. On the contrary, 48 hrs. after p-chlorophenylalanin or subtotal lesion of raphe nuclei, these tracers showed numerous reactive neurons inside or outside the central monoaminergic systems."} {"id": "PMID:157234", "title": "[Spectrum of amidase activity in a mutant of Brevibacterium].", "content": "Brevibacterium R 312 has a fairly non-specific amidase. Following the loss of this enzyme by mutation, the following enzymatic activities could be demonstrated: hydrolysis of urea, formamide, nicotinamide, L-glutamine, glycinamide and L-alpha-amino amids.", "contents": "[Spectrum of amidase activity in a mutant of Brevibacterium]. Brevibacterium R 312 has a fairly non-specific amidase. Following the loss of this enzyme by mutation, the following enzymatic activities could be demonstrated: hydrolysis of urea, formamide, nicotinamide, L-glutamine, glycinamide and L-alpha-amino amids."} {"id": "PMID:157237", "title": "Sanfilippo B syndrome (MPS III B): mild and severe forms within the same sibship.", "content": "Clinical heterogeneity for Sanfilippo B syndrome (MPS III B) in the same family has never been reported previously. We describe two clinically severe cases and one clinically mild case of MPS III B in a Neapolitan sibship. We could not detect N-acetyl-alpha-D-glucosaminidase activity in the sera of either the severe or mild cases. Mucopolysacchariduria mainly due to heparan sulfate excretion was consistently high in the severely affected patients and extremely variable in the mildly affected one.", "contents": "Sanfilippo B syndrome (MPS III B): mild and severe forms within the same sibship. Clinical heterogeneity for Sanfilippo B syndrome (MPS III B) in the same family has never been reported previously. We describe two clinically severe cases and one clinically mild case of MPS III B in a Neapolitan sibship. We could not detect N-acetyl-alpha-D-glucosaminidase activity in the sera of either the severe or mild cases. Mucopolysacchariduria mainly due to heparan sulfate excretion was consistently high in the severely affected patients and extremely variable in the mildly affected one."} {"id": "PMID:157235", "title": "The Croydon Workshop for the parents of severely handicapped school age children.", "content": "A multidisciplinary team of professionals met the parents of 18 severely handicapped children for a series of 10 evening sessions. All children were between 5 and 11 years of age and included six Downs, six non-communicating and six children with rare syndromes or no known diagnosis. The professionals provided practical advice and couselling. They did not adopt one exclusive approach such as behaviour modification, but employed a variety of ideas drawn from several theories of learning and from personal experience. The workshop as well received by both parents and professionals, with an average attendance of 80%. The paper also discusses some of the organizational problems of parent workshops.", "contents": "The Croydon Workshop for the parents of severely handicapped school age children. A multidisciplinary team of professionals met the parents of 18 severely handicapped children for a series of 10 evening sessions. All children were between 5 and 11 years of age and included six Downs, six non-communicating and six children with rare syndromes or no known diagnosis. The professionals provided practical advice and couselling. They did not adopt one exclusive approach such as behaviour modification, but employed a variety of ideas drawn from several theories of learning and from personal experience. The workshop as well received by both parents and professionals, with an average attendance of 80%. The paper also discusses some of the organizational problems of parent workshops."} {"id": "PMID:157238", "title": "The role of IgM rheumatoid factor in experimental immune vasculitis.", "content": "The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis.", "contents": "The role of IgM rheumatoid factor in experimental immune vasculitis. The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis."} {"id": "PMID:157239", "title": "Quantitative assessment of the effects of platelet depletion in the autologous phase of nephrotoxic serum nephritis.", "content": "The effects of platelet depletion with antibody have been studied in two models of the autologous phase of nephrotoxic nephritis in the rabbit. In the 'telescoped' model (animals pre-immunized to sheep IgG injected with sheep nephrotoxic antibody), platelet depletion did not alter intraglomerular fibrin deposition or evidence of glomerular damage, but did significantly reduce proteinuria during the first 3 days of the 5 day experiment. In the 'passive' model (animals injected with hyperimmune rabbit antiserum to sheep IgG 48 hr after sheep nephrotoxic antibody and killed 3 hr later), platelet depletion was associated with significantly fewer intraglomerular polymorphonuclear leucocytes (PMN), but again did not alter intraglomerular fibrin deposition. The results indicate that platelets are involved in the initiation of glomerular PMN localization in the autologous phase, but that fibrin-induced glomerular injury is platelet-independent.", "contents": "Quantitative assessment of the effects of platelet depletion in the autologous phase of nephrotoxic serum nephritis. The effects of platelet depletion with antibody have been studied in two models of the autologous phase of nephrotoxic nephritis in the rabbit. In the 'telescoped' model (animals pre-immunized to sheep IgG injected with sheep nephrotoxic antibody), platelet depletion did not alter intraglomerular fibrin deposition or evidence of glomerular damage, but did significantly reduce proteinuria during the first 3 days of the 5 day experiment. In the 'passive' model (animals injected with hyperimmune rabbit antiserum to sheep IgG 48 hr after sheep nephrotoxic antibody and killed 3 hr later), platelet depletion was associated with significantly fewer intraglomerular polymorphonuclear leucocytes (PMN), but again did not alter intraglomerular fibrin deposition. The results indicate that platelets are involved in the initiation of glomerular PMN localization in the autologous phase, but that fibrin-induced glomerular injury is platelet-independent."} {"id": "PMID:157236", "title": "The regional child assessment centre: the process of referral of cases.", "content": "The various sources of referral to a Regional Child Assessment Centre are enumerated. The question of referrals from paramedicals, education and social services and from parents are discussed.", "contents": "The regional child assessment centre: the process of referral of cases. The various sources of referral to a Regional Child Assessment Centre are enumerated. The question of referrals from paramedicals, education and social services and from parents are discussed."} {"id": "PMID:157244", "title": "Diagnosis of an abdominal aortic graft abscess by combined ultrasonography and scintigraphy.", "content": "A case of an abdominal aortic graft abscess is presented to demonstrate a diagnostic approach using 'B' mode ultrasonography and gallium scintigraphy.", "contents": "Diagnosis of an abdominal aortic graft abscess by combined ultrasonography and scintigraphy. A case of an abdominal aortic graft abscess is presented to demonstrate a diagnostic approach using 'B' mode ultrasonography and gallium scintigraphy."} {"id": "PMID:157241", "title": "Pharmacological profile of a new coronary vasodilator drug, 2-nicotinamidoethyl nitrate (SG-75).", "content": "1. In anaesthetized, open-chest dogs, 2-nicotinamidoethyl nitrate (SG-75) administered intravenously (0.3-1 mg/kg) or intraduodenally (3 mg/kg) produced decrease in systemic blood pressure, coronary resistance, heart rate and an increase in coronary sinus outflow, but virtually no change in myocardial oxygen consumption and atrioventricular conduction. The effects of SG-75 administered intraduodenally emerged within a few minutes after dosing and lasted over about 1 h. 2. In isolated, blood-perfused sino-atrial node preparations of the dog SG-75 administered into the sinus node artery decreased slightly sinus rate at the dose which doubled blood flow through the artery. 3. In isolated, blood-perfused atrioventricular node preparations of the dog SG-75 administered into the atrioventricular node artery did not impair atrioventricular conduction even in doses which increased blood flow through the artery to more than twice the basal level. 4. In isolated, blood-perfused papillary muscle preparations of the dog SG-75 administered into the anterior septal artery scarely affected force of contraction of the papillary muscle at the dose which doubled blood flow through the artery, although in further large doses it produced a transient decrease in the force of contraction. In extremely large doses it produced ventricular fibrillation. 5. In anaesthetized, open-chest dogs in which cardiac input was kept constant SG-75 (0.01-1 mg/kg) administered into the ascending aorta increased venous return without changing systemic output. 6. 2-Nicotinamidoethyl alcohol, a denitrated compound of SG-75, had no vasodilator action in doses comparable to those of the parent compound. 7. These results indicate SG-75 to be a potential antianginal drug having no cardiodepressant actions but having properties uncharacteristic of the nitrates.", "contents": "Pharmacological profile of a new coronary vasodilator drug, 2-nicotinamidoethyl nitrate (SG-75). 1. In anaesthetized, open-chest dogs, 2-nicotinamidoethyl nitrate (SG-75) administered intravenously (0.3-1 mg/kg) or intraduodenally (3 mg/kg) produced decrease in systemic blood pressure, coronary resistance, heart rate and an increase in coronary sinus outflow, but virtually no change in myocardial oxygen consumption and atrioventricular conduction. The effects of SG-75 administered intraduodenally emerged within a few minutes after dosing and lasted over about 1 h. 2. In isolated, blood-perfused sino-atrial node preparations of the dog SG-75 administered into the sinus node artery decreased slightly sinus rate at the dose which doubled blood flow through the artery. 3. In isolated, blood-perfused atrioventricular node preparations of the dog SG-75 administered into the atrioventricular node artery did not impair atrioventricular conduction even in doses which increased blood flow through the artery to more than twice the basal level. 4. In isolated, blood-perfused papillary muscle preparations of the dog SG-75 administered into the anterior septal artery scarely affected force of contraction of the papillary muscle at the dose which doubled blood flow through the artery, although in further large doses it produced a transient decrease in the force of contraction. In extremely large doses it produced ventricular fibrillation. 5. In anaesthetized, open-chest dogs in which cardiac input was kept constant SG-75 (0.01-1 mg/kg) administered into the ascending aorta increased venous return without changing systemic output. 6. 2-Nicotinamidoethyl alcohol, a denitrated compound of SG-75, had no vasodilator action in doses comparable to those of the parent compound. 7. These results indicate SG-75 to be a potential antianginal drug having no cardiodepressant actions but having properties uncharacteristic of the nitrates."} {"id": "PMID:157246", "title": "Basal ganglia calcification in Down's syndrome.", "content": "Basal ganglia calcification has been observed in autopsy material of 7% of children suffering from Down's Syndrome. The incidence of this finding in the general neurological population is approx. 0.3%. The present report is the first case of Down's Syndrome with basal ganglia calcification diagnosed in life by computed axial tomography. This case illustrates that dense basal ganglia calcification can exist with no signs or symptoms of a movement disorder.", "contents": "Basal ganglia calcification in Down's syndrome. Basal ganglia calcification has been observed in autopsy material of 7% of children suffering from Down's Syndrome. The incidence of this finding in the general neurological population is approx. 0.3%. The present report is the first case of Down's Syndrome with basal ganglia calcification diagnosed in life by computed axial tomography. This case illustrates that dense basal ganglia calcification can exist with no signs or symptoms of a movement disorder."} {"id": "PMID:157249", "title": "Contact dermatitis from hydrazine derivatives.", "content": "A 36-year-old man who worked at a chemical factory manifested contact dermatitis due to hydrazine derivatives. Thirty workers out of 130 in this factory were suspected of contracting contact dermatitis on exposed areas. Aminoguanidine hydrochloride, a blender for chicken feed, and the precursor and intermediate products of 3-amino-1,2,4-triazole, a herbicide, were found to be allergens for this contact dermatitis.", "contents": "Contact dermatitis from hydrazine derivatives. A 36-year-old man who worked at a chemical factory manifested contact dermatitis due to hydrazine derivatives. Thirty workers out of 130 in this factory were suspected of contracting contact dermatitis on exposed areas. Aminoguanidine hydrochloride, a blender for chicken feed, and the precursor and intermediate products of 3-amino-1,2,4-triazole, a herbicide, were found to be allergens for this contact dermatitis."} {"id": "PMID:157250", "title": "Primary irritant dermatitis from topical clioquinol.", "content": "During the 2-year period 1976--1977, seven patients were studied with primary irritant dermatitis from topical preparations containing clioquinol. During the same period contact hypersensitivity to the compound was recorded in 35 eczema patients. Six of the seven patients with clioquinol irritancy had used creams containing 3% large crystal clioquinol and fluorinated steroids. One patient had used 6% small crystal clioquinol cream. Challenge tests with 3% small crystal and large crystal clioquinol creams showed that crystal size did not affect the appearance of irritant dermatitis.", "contents": "Primary irritant dermatitis from topical clioquinol. During the 2-year period 1976--1977, seven patients were studied with primary irritant dermatitis from topical preparations containing clioquinol. During the same period contact hypersensitivity to the compound was recorded in 35 eczema patients. Six of the seven patients with clioquinol irritancy had used creams containing 3% large crystal clioquinol and fluorinated steroids. One patient had used 6% small crystal clioquinol cream. Challenge tests with 3% small crystal and large crystal clioquinol creams showed that crystal size did not affect the appearance of irritant dermatitis."} {"id": "PMID:157257", "title": "Ostertagiosis in captive bison in New York State: report of nine cases.", "content": "Type II ostertagiosis was found at necropsy in 9 American bison (Bison bison) from 3 farms in New York. Clinical signs included severe diarrhea, emaciation, unthrifty coats, anemia, and weakness. In severely affected animals, the macroscopic abomasal changes consisted of irregular thickening and edema of the mucosa, resulting in a pebbly or morocco-leather appearance. Microscopically, many gastric pits and glands were dilated, lined by hyperplastic epithelium, and contained nematode sections or debris. Parasites recovered included Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus lerouxi, Cooperia oncophora, Haemonchus contortus, Nematodirus helvetianus, Trichuris discolor, Setaria labiato-papillosa, Dictyocaulus viviparus, Hypoderma lineatum, and Sarcocystis sp. Nodules in the small and large intestine were attributed to Oesophagostomum sp. Trichostrongylus lerouxi, Trichuris discolor, and Nematodirus helvetianus are reported from bison for the first time.", "contents": "Ostertagiosis in captive bison in New York State: report of nine cases. Type II ostertagiosis was found at necropsy in 9 American bison (Bison bison) from 3 farms in New York. Clinical signs included severe diarrhea, emaciation, unthrifty coats, anemia, and weakness. In severely affected animals, the macroscopic abomasal changes consisted of irregular thickening and edema of the mucosa, resulting in a pebbly or morocco-leather appearance. Microscopically, many gastric pits and glands were dilated, lined by hyperplastic epithelium, and contained nematode sections or debris. Parasites recovered included Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus lerouxi, Cooperia oncophora, Haemonchus contortus, Nematodirus helvetianus, Trichuris discolor, Setaria labiato-papillosa, Dictyocaulus viviparus, Hypoderma lineatum, and Sarcocystis sp. Nodules in the small and large intestine were attributed to Oesophagostomum sp. Trichostrongylus lerouxi, Trichuris discolor, and Nematodirus helvetianus are reported from bison for the first time."} {"id": "PMID:157261", "title": "Generalized perforating granuloma annulare: a case report and review of the literature.", "content": "A nineteen year old girl with mongolism and generalized perforating granuloma annulare of the lower legs is presented herein. Skin biopsy specimens showed dermal necrobiosis and epidermal perforation. The literature is reviewed and summarized. The lesions have been characterized as small, often umbilicated papules occurring in large numbers on the extremities.", "contents": "Generalized perforating granuloma annulare: a case report and review of the literature. A nineteen year old girl with mongolism and generalized perforating granuloma annulare of the lower legs is presented herein. Skin biopsy specimens showed dermal necrobiosis and epidermal perforation. The literature is reviewed and summarized. The lesions have been characterized as small, often umbilicated papules occurring in large numbers on the extremities."} {"id": "PMID:157262", "title": "Cutaneous inoculation tuberculosis: prosector's wart occurring in a physician.", "content": "Cutaneous inoculation tuberculosis may occur either a primary or secondary infection. When the condition occurs in medical or laboratory personnel after contact with tuberculous material the term \"prosector's wart\" is often used. A case is reported in a physician following trauma during an autopsy on a tuberculous patient.", "contents": "Cutaneous inoculation tuberculosis: prosector's wart occurring in a physician. Cutaneous inoculation tuberculosis may occur either a primary or secondary infection. When the condition occurs in medical or laboratory personnel after contact with tuberculous material the term \"prosector's wart\" is often used. A case is reported in a physician following trauma during an autopsy on a tuberculous patient."} {"id": "PMID:157263", "title": "Annular pompholyx.", "content": "The common manifestation of pompholyx is easily recognized by the clinician. Morphologic variants are known in which the predominant lesions are pustules or desquamation with or without erythema. A patient is described herein whose eruption was composed mainly of arciform, annular, and target-like vesicles. Pompholyx (bubble) is a preferred term because \"dyshidrosis\" denotes a dysfunction of sweating, which does not occur in this condition. The causes of this eruption have not been determined, but it is likely that a certain genetic predisposition and multiple environmental factors are responsible. Pompholyx should be considered in the differential diagnosis of eruptions with annular pattern.", "contents": "Annular pompholyx. The common manifestation of pompholyx is easily recognized by the clinician. Morphologic variants are known in which the predominant lesions are pustules or desquamation with or without erythema. A patient is described herein whose eruption was composed mainly of arciform, annular, and target-like vesicles. Pompholyx (bubble) is a preferred term because \"dyshidrosis\" denotes a dysfunction of sweating, which does not occur in this condition. The causes of this eruption have not been determined, but it is likely that a certain genetic predisposition and multiple environmental factors are responsible. Pompholyx should be considered in the differential diagnosis of eruptions with annular pattern."} {"id": "PMID:157264", "title": "Treatment of acne with 5% benzoyl peroxide gel or 0.05% retinoic acid cream.", "content": "In a parallel group comparison of a 5% benzoyl peroxide gel with a 0.05% retinoic acid cream, in moderate facial acne vulgaris, significantly more patients in the benzoyl peroxide group experienced overall excellent results than did those in the other group. Both medications, however, were effective in reducing the numbers of both inflammatory and noninflammatory lesions. The benzoyl peroxide gel appeared to produce a more rapid effect on inflammatory lesions than did retinoic acid, and produced significantly less peeling.", "contents": "Treatment of acne with 5% benzoyl peroxide gel or 0.05% retinoic acid cream. In a parallel group comparison of a 5% benzoyl peroxide gel with a 0.05% retinoic acid cream, in moderate facial acne vulgaris, significantly more patients in the benzoyl peroxide group experienced overall excellent results than did those in the other group. Both medications, however, were effective in reducing the numbers of both inflammatory and noninflammatory lesions. The benzoyl peroxide gel appeared to produce a more rapid effect on inflammatory lesions than did retinoic acid, and produced significantly less peeling."} {"id": "PMID:157270", "title": "Influence of 19-nor-deoxycorticosterone on blood pressure, saline consumption, and serum electrolytes, corticosterone, and renin activity.", "content": "Young, unilaterally nephrectomized, female Sprague-Dawley rats were given daily sc injections of 19-nor-deoxycorticosterone acetate (19-nor-DOCA) in oil at a dosage of 100 micrograms/day for 21 days and twice that amount for a further 11 days. One group drank distilled water and another drank 1% NaCl solution. Comparable control groups received oil injections. Another group received DOCA at the same steroid dosage and drank saline. Both 19-nor-DOCA-treated groups rapidly became hypertensive and developed cardiac hypertrophy, as did those given DOCA and saline. Saline consumption was greater in rats receiving 19-nor-DOCA, than in those given DOCA. Rats injected with 19-nor-DOCA and given water to drink showed enhanced growth and developed thymus enlargement and displayed hypokalemia and a reduction in both serum renin activity and corticosterone concentration. Plasma sodium concentration was not affected by any form of treatment. Clearly, 19-nor-DOCA is a potent mineralocorticoid and hypertensogenic agent. Since the parent steroid is known to be present abundantly in the urine of rats with regenerating adrenal glands, although circulating amounts have not yet been ascertained in that circumstance, it may be etiologically involved in adrenal regeneration hypertension, which such rats are prone to develop.", "contents": "Influence of 19-nor-deoxycorticosterone on blood pressure, saline consumption, and serum electrolytes, corticosterone, and renin activity. Young, unilaterally nephrectomized, female Sprague-Dawley rats were given daily sc injections of 19-nor-deoxycorticosterone acetate (19-nor-DOCA) in oil at a dosage of 100 micrograms/day for 21 days and twice that amount for a further 11 days. One group drank distilled water and another drank 1% NaCl solution. Comparable control groups received oil injections. Another group received DOCA at the same steroid dosage and drank saline. Both 19-nor-DOCA-treated groups rapidly became hypertensive and developed cardiac hypertrophy, as did those given DOCA and saline. Saline consumption was greater in rats receiving 19-nor-DOCA, than in those given DOCA. Rats injected with 19-nor-DOCA and given water to drink showed enhanced growth and developed thymus enlargement and displayed hypokalemia and a reduction in both serum renin activity and corticosterone concentration. Plasma sodium concentration was not affected by any form of treatment. Clearly, 19-nor-DOCA is a potent mineralocorticoid and hypertensogenic agent. Since the parent steroid is known to be present abundantly in the urine of rats with regenerating adrenal glands, although circulating amounts have not yet been ascertained in that circumstance, it may be etiologically involved in adrenal regeneration hypertension, which such rats are prone to develop."} {"id": "PMID:157266", "title": "Monoamines and sexual behaviour in non-human primates.", "content": "The experiments described were concerned with elucidating the involvement of monoamines in the sexual behaviour of rhesus monkeys. The measurement of perturbations in the levels and turnover of the acid metabolites of serotonin and dopamine in cisternal cerebrospinal fluid, occurring in response to hormonal manipulations which alter proceptivity and receptivity, has not clarified the ways in which hormones and amines interact. However, the use of psychoactive drugs which alter the activity of monamine neurons in the brain has demonstrated that sexual activity can be profoundly influenced by such procedures. Thus, depletion of serotonin (5-hydroxytryptamine) in the brain using p-chlorophenylalanine reversed the decrease in proceptivity that followed adrenalectomy. Conversely, inhibition of serotonin uptake using chlorimipramine reduced proceptivity and receptivity to very low levels. Both findings point to the apparently important role of serotoninergic neurons in the control of sexual behaviour. Low doses of the dopamine agonist alpha-bromocriptine enhanced the proceptivity of female rhesus monkeys but high doses had no such effect. This behavioural change was not related to the concomitant suppression of serum prolactin and may have been related to presynaptic actions of the drug in a manner postulated to explain similar behavioural effects in rats. The beta-blocker oxprenolol had the interesting property of improving the sexual performance of male rhesus monkeys, a behavioural effect consistent with an anxiolytic action, although endocrine (prolactin, cortisol) measures did not provide support for such a view. Defining the nature of the interaction between hormones and monoamine-containing neurons in the brain in behavioural contexts is shown to depend largely on the application of precise neuroanatomical and neuropharmacological techniques. However, the use of systemic treatment with psychoactive drugs used widely in clinical practice, in carefully controlled, behavioural and and endocrine experiments, is likely to provide invaluable information on where and how to investigate the neural mechanisms involved.", "contents": "Monoamines and sexual behaviour in non-human primates. The experiments described were concerned with elucidating the involvement of monoamines in the sexual behaviour of rhesus monkeys. The measurement of perturbations in the levels and turnover of the acid metabolites of serotonin and dopamine in cisternal cerebrospinal fluid, occurring in response to hormonal manipulations which alter proceptivity and receptivity, has not clarified the ways in which hormones and amines interact. However, the use of psychoactive drugs which alter the activity of monamine neurons in the brain has demonstrated that sexual activity can be profoundly influenced by such procedures. Thus, depletion of serotonin (5-hydroxytryptamine) in the brain using p-chlorophenylalanine reversed the decrease in proceptivity that followed adrenalectomy. Conversely, inhibition of serotonin uptake using chlorimipramine reduced proceptivity and receptivity to very low levels. Both findings point to the apparently important role of serotoninergic neurons in the control of sexual behaviour. Low doses of the dopamine agonist alpha-bromocriptine enhanced the proceptivity of female rhesus monkeys but high doses had no such effect. This behavioural change was not related to the concomitant suppression of serum prolactin and may have been related to presynaptic actions of the drug in a manner postulated to explain similar behavioural effects in rats. The beta-blocker oxprenolol had the interesting property of improving the sexual performance of male rhesus monkeys, a behavioural effect consistent with an anxiolytic action, although endocrine (prolactin, cortisol) measures did not provide support for such a view. Defining the nature of the interaction between hormones and monoamine-containing neurons in the brain in behavioural contexts is shown to depend largely on the application of precise neuroanatomical and neuropharmacological techniques. However, the use of systemic treatment with psychoactive drugs used widely in clinical practice, in carefully controlled, behavioural and and endocrine experiments, is likely to provide invaluable information on where and how to investigate the neural mechanisms involved."} {"id": "PMID:157271", "title": "New evidences for participation of biogenic monoamines in androgen-dependent sexual differentiation of hypothalamic control of gonadotropin secretion in rats.", "content": "Corpora lutea have been found in the ovarian tissue transplanted into the anterior ocular chamber of castrated two-month-old male rats receiving on 3rd through 7th post-natal days alpha-methyl-p-tyrosine or p-chlorophenylalanine. Administration of these agents in combination with testosterone propionate to newborn female rats prevented essentially development of the anovulatory syndrome and maintained a normal picture of vaginal smears, ovarian and uterine structure as well as cyclic changes of adenohypophyseal and blood plasma lutropin contents and normal levels of estradiol and progesterone in the blood plasma except of progesterone level in animals receiving alpha-methyl-p-tyrosine. The preventive effect of the adrenoblocking agents droperidol and propranolol was weak and inconstant. Results suggest participation of catecholamines and serotonin in the androgen-dependent sexual differentiation of the brain in rats.", "contents": "New evidences for participation of biogenic monoamines in androgen-dependent sexual differentiation of hypothalamic control of gonadotropin secretion in rats. Corpora lutea have been found in the ovarian tissue transplanted into the anterior ocular chamber of castrated two-month-old male rats receiving on 3rd through 7th post-natal days alpha-methyl-p-tyrosine or p-chlorophenylalanine. Administration of these agents in combination with testosterone propionate to newborn female rats prevented essentially development of the anovulatory syndrome and maintained a normal picture of vaginal smears, ovarian and uterine structure as well as cyclic changes of adenohypophyseal and blood plasma lutropin contents and normal levels of estradiol and progesterone in the blood plasma except of progesterone level in animals receiving alpha-methyl-p-tyrosine. The preventive effect of the adrenoblocking agents droperidol and propranolol was weak and inconstant. Results suggest participation of catecholamines and serotonin in the androgen-dependent sexual differentiation of the brain in rats."} {"id": "PMID:157274", "title": "Fiber composition, fiber size and enzyme activities in vastus lateralis of elite athletes involved in high intensity exercise.", "content": "In order to determine the influence of an extensive history of participation in high intensity activity on muscle fiber type, fiber size, and metabolic profile, elite ice hockey players were selected for investigation from three different leagues. Biopsy samples from the vastus lateralis muscle were obtained from different groups of players prior to and following the season and compared with control subjects. No significant differences were found in the percentage (49.6 vs. 43.8%) or the size of the ST fibers between the elite athletes and the control group, nor was there any significant alteration following the season of play in these variables. For the FT fiber subgroups, a reduction in the FTb (12.2 vs. 3.9%) and an increase in FTa (38.0 to 45.2%) fiber populations occurred over the season. Similarly, increases in fiber area were observed for both FT subgroups pre to post season. Of the enzymes studied only 3-hydroxyacyl CoA dehydrogenase was elevated in the post season measures, while total phosphorylase and phosphofructokinase were significantly lower. The metabolic pattern exhibited does not appear to be substantially different from what would be expected from an untrained group of similar fiber distribution.", "contents": "Fiber composition, fiber size and enzyme activities in vastus lateralis of elite athletes involved in high intensity exercise. In order to determine the influence of an extensive history of participation in high intensity activity on muscle fiber type, fiber size, and metabolic profile, elite ice hockey players were selected for investigation from three different leagues. Biopsy samples from the vastus lateralis muscle were obtained from different groups of players prior to and following the season and compared with control subjects. No significant differences were found in the percentage (49.6 vs. 43.8%) or the size of the ST fibers between the elite athletes and the control group, nor was there any significant alteration following the season of play in these variables. For the FT fiber subgroups, a reduction in the FTb (12.2 vs. 3.9%) and an increase in FTa (38.0 to 45.2%) fiber populations occurred over the season. Similarly, increases in fiber area were observed for both FT subgroups pre to post season. Of the enzymes studied only 3-hydroxyacyl CoA dehydrogenase was elevated in the post season measures, while total phosphorylase and phosphofructokinase were significantly lower. The metabolic pattern exhibited does not appear to be substantially different from what would be expected from an untrained group of similar fiber distribution."} {"id": "PMID:157275", "title": "Intracellular localization of exogenous beta-glucuronidase in cultured skin fibroblasts.", "content": "The intracellular localization of exogenously supplied human platelet beta-glucuronidase in cultured skin fibroblasts derived from a beta-glucuronidase-deficient patient was studied. Four cellular fractions were obtained by differential speed centrifugation. Following two days of incubation, the exogenously supplied enzyme exhibited a distribution pattern identical to that of endogenous beta-hexosaminidase. Disruption of membranes by freezing and thawing caused a 35% increase of the enzyme activity, thus indicating a latent activity following the internalization. This indicated localization in the lysosomal fractions. Longer incubation periods led to an intracellular shift of the engulfed enzyme from the lighter lysosomal fraction to heavier particles. Once located in the heavier fraction, the enzyme was relatively stable, and participated in the catabolism of 35S-labeled mucopolysaccharides which had accumulated in the lysosomes of these fibroblasts. A marked reduction in the accumulated mucopolysaccharides of the lysosomal fraction was observed following addition of the enzyme. This was accompanied by the formation of smaller sized molecules.", "contents": "Intracellular localization of exogenous beta-glucuronidase in cultured skin fibroblasts. The intracellular localization of exogenously supplied human platelet beta-glucuronidase in cultured skin fibroblasts derived from a beta-glucuronidase-deficient patient was studied. Four cellular fractions were obtained by differential speed centrifugation. Following two days of incubation, the exogenously supplied enzyme exhibited a distribution pattern identical to that of endogenous beta-hexosaminidase. Disruption of membranes by freezing and thawing caused a 35% increase of the enzyme activity, thus indicating a latent activity following the internalization. This indicated localization in the lysosomal fractions. Longer incubation periods led to an intracellular shift of the engulfed enzyme from the lighter lysosomal fraction to heavier particles. Once located in the heavier fraction, the enzyme was relatively stable, and participated in the catabolism of 35S-labeled mucopolysaccharides which had accumulated in the lysosomes of these fibroblasts. A marked reduction in the accumulated mucopolysaccharides of the lysosomal fraction was observed following addition of the enzyme. This was accompanied by the formation of smaller sized molecules."} {"id": "PMID:157276", "title": "3' Esters of ADP as energy-transfer inhibitors and probes of the catalytic site of oxidative phosphorylation.", "content": "1. A large series of 3' esters of ADP has been synthesized. Several of these can serve as photoaffinity labels; others exhibit fluorescent properties. The corresponding AMP and ATP derivatives have also been synthesized in some cases. 2. The influence of the 3'-O-acyl nucleotides on energy-linked functions of beef-heart submitochondrial particles has been investigated. The following results were obtained. a) 3'Esters of ADP are powerful and highly specific inhibitors of oxidative phosphorylation. The inhibition is competitive to ADP and Ki values as low as 0.05 microM, for the 3'-O-(1)naphthoyl ester of ADP, could be observed. b) The inhibition of oxidative phosphorylation by 3' esters of ADP appears to be non-competitive versus inorganic phosphate. c) The nucleotide analogs are not phosphorylated themselves. The corresponding ATP analogs can not drive energy-linked process. d) The 3' esters of AMP are ineffective as inhibitors, whereas the ATP derivatives are only comparatively weak inhibitors. e) Uncoupled or solubilized ATPase is almost two orders of magnitude less sensitive against inhibition by 3' esters than coupled systems. The analogs exert maximal inhibition specifically in systems involving an 'energized' state of the coupling device. f) Azido-group-bearing analogs can be used for irreversible photoinactivation of the coupling ATPase. Photoinactivation also is most efficient when carried out with 'energized' particles. g) The inhibitory properties are similar also in ATP-driven NAD+ reduction by succinate, and in the uncoupler-sensitive ATP in equilibrium with Pi exchange. The required concentrations for half-maximal inhibition are somewhat higher than in oxidative phosphorylation, but lower than with uncoupled ATPase. 3. From molecular models, from substituent properties, and from the conditions required for inhibition it is concluded that these highly effective analogs of ADP may act as conformation-specific probes at the catalytic site of oxidative phosphorylation. The results are interpreted in terms of a model suggesting that, in the process of ATP synthesis, a hydrophobic cavity on the enzyme is exposed only in the energized state, accepting the large 3' substituent. The substituent is assumed to inhibit phosphoryl transfer and/or conformational transitions inherent in the process of ADP phosphorylation by steric hinderance.", "contents": "3' Esters of ADP as energy-transfer inhibitors and probes of the catalytic site of oxidative phosphorylation. 1. A large series of 3' esters of ADP has been synthesized. Several of these can serve as photoaffinity labels; others exhibit fluorescent properties. The corresponding AMP and ATP derivatives have also been synthesized in some cases. 2. The influence of the 3'-O-acyl nucleotides on energy-linked functions of beef-heart submitochondrial particles has been investigated. The following results were obtained. a) 3'Esters of ADP are powerful and highly specific inhibitors of oxidative phosphorylation. The inhibition is competitive to ADP and Ki values as low as 0.05 microM, for the 3'-O-(1)naphthoyl ester of ADP, could be observed. b) The inhibition of oxidative phosphorylation by 3' esters of ADP appears to be non-competitive versus inorganic phosphate. c) The nucleotide analogs are not phosphorylated themselves. The corresponding ATP analogs can not drive energy-linked process. d) The 3' esters of AMP are ineffective as inhibitors, whereas the ATP derivatives are only comparatively weak inhibitors. e) Uncoupled or solubilized ATPase is almost two orders of magnitude less sensitive against inhibition by 3' esters than coupled systems. The analogs exert maximal inhibition specifically in systems involving an 'energized' state of the coupling device. f) Azido-group-bearing analogs can be used for irreversible photoinactivation of the coupling ATPase. Photoinactivation also is most efficient when carried out with 'energized' particles. g) The inhibitory properties are similar also in ATP-driven NAD+ reduction by succinate, and in the uncoupler-sensitive ATP in equilibrium with Pi exchange. The required concentrations for half-maximal inhibition are somewhat higher than in oxidative phosphorylation, but lower than with uncoupled ATPase. 3. From molecular models, from substituent properties, and from the conditions required for inhibition it is concluded that these highly effective analogs of ADP may act as conformation-specific probes at the catalytic site of oxidative phosphorylation. The results are interpreted in terms of a model suggesting that, in the process of ATP synthesis, a hydrophobic cavity on the enzyme is exposed only in the energized state, accepting the large 3' substituent. The substituent is assumed to inhibit phosphoryl transfer and/or conformational transitions inherent in the process of ADP phosphorylation by steric hinderance."} {"id": "PMID:157277", "title": "Properties of the F0F1 ATPase complex from Rhodospirillum rubrum chromatophores, solubilized by Triton X-100.", "content": "1. A cold-stable oligomycin-sensitive F0F1 ATPase complex from chromatophores of Rhodospirillum rubrum FR 1 was solubilized by Triton X-100 and purified by gel filtration. 2. The F0F1 complex is resolved by sodium dodecyl sulfate electrophoresis into 14 polypeptides with approximate molecular weights in the range of 58000--6800; five of these polypeptides are derived from the F1 moiety of the complex which carries the catalytic centers of the enzyme. 3. The purified F0F1 complex is homogeneous according to analytical ultracentrifugation and isoelectric focusing. 4. The molecular weight as determined by gel filtration is about 480 000 +/- 30 000. S020,w is 1.45 +/- 0.1 S and the pI is 5.4. 5. The amino acid composition of the F0F1 complex is compared with the data obtained for the F1 moiety of the enzyme. 6. Quantitative data on the sensitivity to N,N'-dicyclohexyl-carbodiimide as well as kinetic parameters, regarding substrate specificity and dependence of ATPase activity on divalent cations, are reported.", "contents": "Properties of the F0F1 ATPase complex from Rhodospirillum rubrum chromatophores, solubilized by Triton X-100. 1. A cold-stable oligomycin-sensitive F0F1 ATPase complex from chromatophores of Rhodospirillum rubrum FR 1 was solubilized by Triton X-100 and purified by gel filtration. 2. The F0F1 complex is resolved by sodium dodecyl sulfate electrophoresis into 14 polypeptides with approximate molecular weights in the range of 58000--6800; five of these polypeptides are derived from the F1 moiety of the complex which carries the catalytic centers of the enzyme. 3. The purified F0F1 complex is homogeneous according to analytical ultracentrifugation and isoelectric focusing. 4. The molecular weight as determined by gel filtration is about 480 000 +/- 30 000. S020,w is 1.45 +/- 0.1 S and the pI is 5.4. 5. The amino acid composition of the F0F1 complex is compared with the data obtained for the F1 moiety of the enzyme. 6. Quantitative data on the sensitivity to N,N'-dicyclohexyl-carbodiimide as well as kinetic parameters, regarding substrate specificity and dependence of ATPase activity on divalent cations, are reported."} {"id": "PMID:157278", "title": "Mitochondrial ATPase complex of Aspergillus nidulans and the dicyclohexylcarbodiimide-binding protein.", "content": "The dicyclohexylcarbodiimide-binding protein of Aspergillus nidulans has been identified as the smallest subunit of the mitochondrial ATPase complex, and has a molecular weight of approximately 8000. It is extractable from whole mitochondria and from the purified enzyme in neutral chloroform/methanol, contains 30% polar amino acids, and the N-terminal amino acid has been identified as tyrosine. Using a double-labelling technique in the absence and presence of cycloheximide, followed by immunoprecipitation of the enzyme complex with antiserum against Neuospora crassa F1 ATPase, it has been shown that this subunit is synthesized on cytoplasmic ribosomes.", "contents": "Mitochondrial ATPase complex of Aspergillus nidulans and the dicyclohexylcarbodiimide-binding protein. The dicyclohexylcarbodiimide-binding protein of Aspergillus nidulans has been identified as the smallest subunit of the mitochondrial ATPase complex, and has a molecular weight of approximately 8000. It is extractable from whole mitochondria and from the purified enzyme in neutral chloroform/methanol, contains 30% polar amino acids, and the N-terminal amino acid has been identified as tyrosine. Using a double-labelling technique in the absence and presence of cycloheximide, followed by immunoprecipitation of the enzyme complex with antiserum against Neuospora crassa F1 ATPase, it has been shown that this subunit is synthesized on cytoplasmic ribosomes."} {"id": "PMID:157281", "title": "Further studies on the role of cholinergic mechanisms in the development of increased naloxone potency in mice.", "content": "Using the abdominal constriction response in mice, it was shown that pretreatment with either pilocarpine (5.0 mg/kg, s.c.) or oxotremorine (0.05--0.10 mg/kg s.c) caused a small but significant potentiation of the antinociceptive effect of morphine and the antagonistic action of naloxone. The potentiation of naloxone was considerably augmented following pretreatment with morphine plus either pilocarpine (2.5--5.0 mg/kg) or oxotremorine (0.05--0.10 mg/kg) as compared with any of these drugs given alone. Pretreatment with atropine sulphate (2.0 mg/kg, s.c.) had no effect on naloxone potency nor on the antinociceptive activity of morphine, but somewhat reduced that of pilocarpine and oxotremorine. Atropine abolished the ability of morphine pretreatment to enhance naloxone potency, and greatly reduced the augmenting effect of morphine plus the muscarinic receptor agonist drugs. It was also shown that oxotremorine reduced the development of dependence on morphine as tested by naloxone-precipitated jumping. These results agreed well with those reported using anticholinesterase drugs and add further evidence that the cholinergic system does play a role in the development of increased naloxone potency caused by morphine pretreatment. The increased naloxone potency does not seem to be related to the development of \"acute dependence\" on morphine.", "contents": "Further studies on the role of cholinergic mechanisms in the development of increased naloxone potency in mice. Using the abdominal constriction response in mice, it was shown that pretreatment with either pilocarpine (5.0 mg/kg, s.c.) or oxotremorine (0.05--0.10 mg/kg s.c) caused a small but significant potentiation of the antinociceptive effect of morphine and the antagonistic action of naloxone. The potentiation of naloxone was considerably augmented following pretreatment with morphine plus either pilocarpine (2.5--5.0 mg/kg) or oxotremorine (0.05--0.10 mg/kg) as compared with any of these drugs given alone. Pretreatment with atropine sulphate (2.0 mg/kg, s.c.) had no effect on naloxone potency nor on the antinociceptive activity of morphine, but somewhat reduced that of pilocarpine and oxotremorine. Atropine abolished the ability of morphine pretreatment to enhance naloxone potency, and greatly reduced the augmenting effect of morphine plus the muscarinic receptor agonist drugs. It was also shown that oxotremorine reduced the development of dependence on morphine as tested by naloxone-precipitated jumping. These results agreed well with those reported using anticholinesterase drugs and add further evidence that the cholinergic system does play a role in the development of increased naloxone potency caused by morphine pretreatment. The increased naloxone potency does not seem to be related to the development of \"acute dependence\" on morphine."} {"id": "PMID:157282", "title": "Placental barrier against circulating immune complexes. A study in pregnant guinea pigs using maternal injection of horseradish peroxidase soluble immune complexes.", "content": "It is not rare that the so-called immune complex diseases (some of which were recently supposed to be induced by the biological effects of circulating antigen-antibody immune complexes) are concomitantly present in pregnant females. But there have been very few reports of congenital immune complex diseases.", "contents": "Placental barrier against circulating immune complexes. A study in pregnant guinea pigs using maternal injection of horseradish peroxidase soluble immune complexes. It is not rare that the so-called immune complex diseases (some of which were recently supposed to be induced by the biological effects of circulating antigen-antibody immune complexes) are concomitantly present in pregnant females. But there have been very few reports of congenital immune complex diseases."} {"id": "PMID:157283", "title": "Automated image analysis for measurements of morphological reactions of blood vessels of the microvascular system.", "content": "Using a modification of the Mg-ATPase reaction, the arterial blood vessels of the microcirculatory bed of the rat including the smallest precapillary vessels are visualized in a grey-level difference against their environment which permits to utilize the automatic image analyser QUANTIMET 720 and the programmable desk-top calculator HEWLETT-PACKARD 9100B. The article describes the method for preparing the sections, the measuring procedure, and the statistical verification of the results by means of the computer assisted two-way analysis of variance as well as studies demonstrating the reliability of the method. It is concluded that the procedure at heart, skeletal muscle and pancreas specimens of the rat demonstrates reliably and effectively changes of the number of vessels and the projected whole vessel wall area as well as differences of enzyme activities. Thus it is possible to detect structural wall reactions and enzyme histochemical changes of arterial blood vessels of the microvasculatory bed including its smallest precapillaries which have been practically inaccessible to histomorphometrical investigations in the past.", "contents": "Automated image analysis for measurements of morphological reactions of blood vessels of the microvascular system. Using a modification of the Mg-ATPase reaction, the arterial blood vessels of the microcirculatory bed of the rat including the smallest precapillary vessels are visualized in a grey-level difference against their environment which permits to utilize the automatic image analyser QUANTIMET 720 and the programmable desk-top calculator HEWLETT-PACKARD 9100B. The article describes the method for preparing the sections, the measuring procedure, and the statistical verification of the results by means of the computer assisted two-way analysis of variance as well as studies demonstrating the reliability of the method. It is concluded that the procedure at heart, skeletal muscle and pancreas specimens of the rat demonstrates reliably and effectively changes of the number of vessels and the projected whole vessel wall area as well as differences of enzyme activities. Thus it is possible to detect structural wall reactions and enzyme histochemical changes of arterial blood vessels of the microvasculatory bed including its smallest precapillaries which have been practically inaccessible to histomorphometrical investigations in the past."} {"id": "PMID:157284", "title": "Normal liver actually possesses a high vascular plasminogen activator activity.", "content": "Blood vessels isolated from the liver of the rat, guinea-pig, rabbit, dog and pig showed histochemically a more or less high plasminogen activator activity. In whole liver sections, the abundant release and diffusion of inhibitors of fibrinolysis from the liver parenchyma during the histochemical procedure, partially or totally mask this high vascular activity.", "contents": "Normal liver actually possesses a high vascular plasminogen activator activity. Blood vessels isolated from the liver of the rat, guinea-pig, rabbit, dog and pig showed histochemically a more or less high plasminogen activator activity. In whole liver sections, the abundant release and diffusion of inhibitors of fibrinolysis from the liver parenchyma during the histochemical procedure, partially or totally mask this high vascular activity."} {"id": "PMID:157285", "title": "Relation between fibrinolytic activity and prostacyclin generation of atherosclerotic artery and dacron prosthetic graft.", "content": "The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel.", "contents": "Relation between fibrinolytic activity and prostacyclin generation of atherosclerotic artery and dacron prosthetic graft. The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel."} {"id": "PMID:157292", "title": "[Decrease in the frequency of muscle spindle discharges during muscle stretching].", "content": "When studying responses of 500 muscle receptors to stretching of the m. triceps of the cat deafferented hindlimb, 23 cases revealed a transient decrease in the firing rate (DFR) of muscle spindles' receptors. The DFR occurs in the same receptor at different forms and rates of stretching approximately at the same area of stretching (\"the DFR area\"). When increasing the rate of stretching, the DFR effect is enhanced. The DFR effect seems to be due to a short-lasting unloading of the spindle area which contains the receptor terminals. The unhomogenous structure of the extrafusal muscle as well as various mechanical properties of the intrafusal muscle fibers can provide necessary conditions for the above effect.", "contents": "[Decrease in the frequency of muscle spindle discharges during muscle stretching]. When studying responses of 500 muscle receptors to stretching of the m. triceps of the cat deafferented hindlimb, 23 cases revealed a transient decrease in the firing rate (DFR) of muscle spindles' receptors. The DFR occurs in the same receptor at different forms and rates of stretching approximately at the same area of stretching (\"the DFR area\"). When increasing the rate of stretching, the DFR effect is enhanced. The DFR effect seems to be due to a short-lasting unloading of the spindle area which contains the receptor terminals. The unhomogenous structure of the extrafusal muscle as well as various mechanical properties of the intrafusal muscle fibers can provide necessary conditions for the above effect."} {"id": "PMID:157301", "title": "Immune complex disease associated with Peroben intake.", "content": "The clinical history and biological investigations of a patient presenting an immune complex disease induced by Peroben are reported. Biological signs were those of a drug-induced lupus syndrome. A provocation test allowed disclosure of its pathomechanism, since during Peroben intake a high C1q binding activity occurred and later regressed, while deposits of IgM and C3 were evidenced in the vessel walls. Complete or partial thrombosis succeeded accompanying a leukocytoclastic vasculitis.", "contents": "Immune complex disease associated with Peroben intake. The clinical history and biological investigations of a patient presenting an immune complex disease induced by Peroben are reported. Biological signs were those of a drug-induced lupus syndrome. A provocation test allowed disclosure of its pathomechanism, since during Peroben intake a high C1q binding activity occurred and later regressed, while deposits of IgM and C3 were evidenced in the vessel walls. Complete or partial thrombosis succeeded accompanying a leukocytoclastic vasculitis."} {"id": "PMID:157304", "title": "Long-term outcome in children with temporal lobe seizures. I: Social outcome and childhood factors.", "content": "One-hundred children, diagnosed as having temporal lobe epilepsy and reported on in 1966, have been followed into adult life. In this 1977 survey they have been coded into four social outcome categories, A, B, C and D. A: 33 per cent are found to be seizure-free and independent; B: 21 per cent are socially and economically independent but are receiving anticonvulsant treatment and are not necessarily seizure-free; C: O9 per cent are dependent either on their parents or in institutions; D: 5 per cent died under the age of 15. Biological factors ascertained and coded in childhood are related to adult outcome. Eight adverse factors emerged: an IQ below 90, onset of seizures before 2 years 4 months, five or more grand mal attacks, temporal lobe seizure frequency of one per day or more, a left-sided focus, the hyperkinetic syndrome, catastrophic rage and special schooling. The presence of first-degree relatives with seizure disorders was a good prognostic sign. Disorderly homes in childhood did not significantly affect adult outcome. All but one of those achieving Group A status had received normal schooling. In general, the prognosis for children with limbic seizures is clear before the end of adolescence. A simple count of the number of childhood adverse factors predicts adult outcome at a high level of significance.", "contents": "Long-term outcome in children with temporal lobe seizures. I: Social outcome and childhood factors. One-hundred children, diagnosed as having temporal lobe epilepsy and reported on in 1966, have been followed into adult life. In this 1977 survey they have been coded into four social outcome categories, A, B, C and D. A: 33 per cent are found to be seizure-free and independent; B: 21 per cent are socially and economically independent but are receiving anticonvulsant treatment and are not necessarily seizure-free; C: O9 per cent are dependent either on their parents or in institutions; D: 5 per cent died under the age of 15. Biological factors ascertained and coded in childhood are related to adult outcome. Eight adverse factors emerged: an IQ below 90, onset of seizures before 2 years 4 months, five or more grand mal attacks, temporal lobe seizure frequency of one per day or more, a left-sided focus, the hyperkinetic syndrome, catastrophic rage and special schooling. The presence of first-degree relatives with seizure disorders was a good prognostic sign. Disorderly homes in childhood did not significantly affect adult outcome. All but one of those achieving Group A status had received normal schooling. In general, the prognosis for children with limbic seizures is clear before the end of adolescence. A simple count of the number of childhood adverse factors predicts adult outcome at a high level of significance."} {"id": "PMID:157305", "title": "Factors affecting walking in a profoundly retarded population.", "content": "A total of 127 children with profound mental retardation were reviewed to determine the age at which walking began. 53 per cent of the children walked at a median age of 30 months. Further sub-classification revealed that both the number of ambulatory children and their age at walking varied with degree of neurological handicap, children with additional neurological problems having a higher median age for beginning to walk. The minimal cognitive level required for walking remains unknown, but is probably less than generally accepted. In this profoundly retarded population, the existence of neurological factors was associated with both increased age at walking and with decreased ability to walk.", "contents": "Factors affecting walking in a profoundly retarded population. A total of 127 children with profound mental retardation were reviewed to determine the age at which walking began. 53 per cent of the children walked at a median age of 30 months. Further sub-classification revealed that both the number of ambulatory children and their age at walking varied with degree of neurological handicap, children with additional neurological problems having a higher median age for beginning to walk. The minimal cognitive level required for walking remains unknown, but is probably less than generally accepted. In this profoundly retarded population, the existence of neurological factors was associated with both increased age at walking and with decreased ability to walk."} {"id": "PMID:157306", "title": "Nerve outgrowth by dorsal root ganglia in vitro: stimulation by inhibitors of DNA metabolism in the absence of exogenous nerve growth factor.", "content": "Dorsal root ganglia from 8-day chick embryos can be stimulated to extend nerve processes in culture by inclusion of cytosine arabinoside (Ara-C) in the culture medium, in the absence of exogenous nerve growth factor (NGF). The degree of stimulation is dose dependent, and is not mimicked by either free cytosine or free arabinose. Since Ara-C is known to inhibit DNA synthesis, other inhibitors of DNA synthesis were tested. Hydroxyurea, fluorodeoxyuridine, and 3 mM thymidine all stimulated nerve outgrowth in the absence of exogenous NGF. In addition, bromodeoxyuridine also stimulated nerve outgrowth. In all cases, stimulation was observable after 24 h of culture, with maximal outgrowth achieved by 72 h of culture. The experimental response was never as large as the response to NGF, but was up to seven times greater than control outgrowth. In all cultures, nerve processes were characterized by growth cones at their distal tips, colchicine-sensitivity, and a high tubulin content visualized by immunofluorescence with anti-tubulin antibody.", "contents": "Nerve outgrowth by dorsal root ganglia in vitro: stimulation by inhibitors of DNA metabolism in the absence of exogenous nerve growth factor. Dorsal root ganglia from 8-day chick embryos can be stimulated to extend nerve processes in culture by inclusion of cytosine arabinoside (Ara-C) in the culture medium, in the absence of exogenous nerve growth factor (NGF). The degree of stimulation is dose dependent, and is not mimicked by either free cytosine or free arabinose. Since Ara-C is known to inhibit DNA synthesis, other inhibitors of DNA synthesis were tested. Hydroxyurea, fluorodeoxyuridine, and 3 mM thymidine all stimulated nerve outgrowth in the absence of exogenous NGF. In addition, bromodeoxyuridine also stimulated nerve outgrowth. In all cases, stimulation was observable after 24 h of culture, with maximal outgrowth achieved by 72 h of culture. The experimental response was never as large as the response to NGF, but was up to seven times greater than control outgrowth. In all cultures, nerve processes were characterized by growth cones at their distal tips, colchicine-sensitivity, and a high tubulin content visualized by immunofluorescence with anti-tubulin antibody."} {"id": "PMID:157307", "title": "Effect of blood, ascites, and tumor cell density on cytocidal action of neocarzinostatin.", "content": "Cytocidal activity of Neocarzinostatin (NCS) was analyzed in vitro by using cultured and ascitic L1210 cells. NCS shows rapid and typical concentration-dependent cytocidal action against L1210 cells. The concentration required for 90% cell-kill (MLD90) and for all 10(6) cell-kill (MIC/10(6)) was 5 x 10(-2) and 4 x 10(-1) microgram/ml, respectively, when L1210/C cells were exposed to NCS at the concentration of 2 x 10(5)/ml in RPMI-1640 medium. When L1210/C cells at the concentration of 1.3 x 10(7)/ml were exposed to NCS, cytocidal activity of NCS decreased, and MLD90 and MIC/10(6) increased to 1.75 x 10(-1) microgram/ml (3.4x) and 2.83 microgram/ml (6.5x), respectively. Also, when a small fraction of whole BDF1 mouse blood, red blood cells, or spleen cells was present in the reaction mixture, cytocidal activity of NCS appeared to decrease. Furthermore, when washed hemorrhagic ascitic L1210 cell suspension was exposed to NCS, 100 times or more concentration of NCS was required for 90% cell-kill or all 10(6) cell-kill. The effect of plasma or serum on cytocidal activity of NCS was minimum. These results indicate that cytocidal activity of NCS is greatly inhibited through contact with tumor cells, blood cells, spleen cells, and/or hemorrhagic ascites. This may be one of the reasons why L1210 cells, which show high sensitivity against NCS in vitro, are less sensitive in vivo. In order to explain these findings, the possibility of inactivation of NCS by the cells or reduction of free active NCS molecules by the binding or adsorption with the cells is discussed. This characteristics in action of NCS should be take into account in clinical use.", "contents": "Effect of blood, ascites, and tumor cell density on cytocidal action of neocarzinostatin. Cytocidal activity of Neocarzinostatin (NCS) was analyzed in vitro by using cultured and ascitic L1210 cells. NCS shows rapid and typical concentration-dependent cytocidal action against L1210 cells. The concentration required for 90% cell-kill (MLD90) and for all 10(6) cell-kill (MIC/10(6)) was 5 x 10(-2) and 4 x 10(-1) microgram/ml, respectively, when L1210/C cells were exposed to NCS at the concentration of 2 x 10(5)/ml in RPMI-1640 medium. When L1210/C cells at the concentration of 1.3 x 10(7)/ml were exposed to NCS, cytocidal activity of NCS decreased, and MLD90 and MIC/10(6) increased to 1.75 x 10(-1) microgram/ml (3.4x) and 2.83 microgram/ml (6.5x), respectively. Also, when a small fraction of whole BDF1 mouse blood, red blood cells, or spleen cells was present in the reaction mixture, cytocidal activity of NCS appeared to decrease. Furthermore, when washed hemorrhagic ascitic L1210 cell suspension was exposed to NCS, 100 times or more concentration of NCS was required for 90% cell-kill or all 10(6) cell-kill. The effect of plasma or serum on cytocidal activity of NCS was minimum. These results indicate that cytocidal activity of NCS is greatly inhibited through contact with tumor cells, blood cells, spleen cells, and/or hemorrhagic ascites. This may be one of the reasons why L1210 cells, which show high sensitivity against NCS in vitro, are less sensitive in vivo. In order to explain these findings, the possibility of inactivation of NCS by the cells or reduction of free active NCS molecules by the binding or adsorption with the cells is discussed. This characteristics in action of NCS should be take into account in clinical use."} {"id": "PMID:157308", "title": "Growth of intraperitoneally transplanted ascites hepatoma, AH39 cells, in the area of gelatin sponge inoculation into the abdominal wall of Donryu rats.", "content": "A piece of gelatin sponge was inoculated submesothelialy in the abdominal wall of female Donryu rats, and 1, 2, 4, 7, 14, or 21 days later, 1 x 10(5) cells of ascites hepatoma AH39 were intraperitoneally transplanted. Tumor cells were detected in the area of gelatin sponge inoculation in each group 2 to 5 days after the transplantation. Generally, the number of rats in which tumor cells were detected was larger in those transplanted with tumor cells within a short period after the gelatin sponge inoculation. Changes in the area of gelatin sponge inoculation and nontreated area in the rats which received intraperitoneal transplantation of the tumor cells on the 1st day after gelatin sponge inoculation were studied. Tumor cells were detected in the area of gelatin sponge inoculation as early as 2 days after the tumor transplantation, whereas they were detected on the 14th day in nontreated areas. Tumor detection was preceded by inflammatory reaction in both cases.", "contents": "Growth of intraperitoneally transplanted ascites hepatoma, AH39 cells, in the area of gelatin sponge inoculation into the abdominal wall of Donryu rats. A piece of gelatin sponge was inoculated submesothelialy in the abdominal wall of female Donryu rats, and 1, 2, 4, 7, 14, or 21 days later, 1 x 10(5) cells of ascites hepatoma AH39 were intraperitoneally transplanted. Tumor cells were detected in the area of gelatin sponge inoculation in each group 2 to 5 days after the transplantation. Generally, the number of rats in which tumor cells were detected was larger in those transplanted with tumor cells within a short period after the gelatin sponge inoculation. Changes in the area of gelatin sponge inoculation and nontreated area in the rats which received intraperitoneal transplantation of the tumor cells on the 1st day after gelatin sponge inoculation were studied. Tumor cells were detected in the area of gelatin sponge inoculation as early as 2 days after the tumor transplantation, whereas they were detected on the 14th day in nontreated areas. Tumor detection was preceded by inflammatory reaction in both cases."} {"id": "PMID:157309", "title": "Combined effect of BCG and coenzyme Q10 on ATP-ase activity and coenzyme Q content in spleen lymphocytes of tumor-bearing rats.", "content": "Effect of BCG, coenzyme Q10, or their combination on ATPase activity in spleen lymphocytes of tumor-bearing rats was investigated in relation to changes in the content of individual coenzyme Q homologs in these cells. Contents of both coenzyme Q9 and Q10 in spleen lymphocytes significantly decreased in the late stage of Donryu rats bearing Sato lung carcinoma. Oligomycin-sensitive ATPase activity in spleen lymphocytes was also significantly depressed in this stage. The depressed, oligomycin-sensitive ATPase activity was significantly recovered by a 3-time intramuscular administration of coenzyme Q10 emulsified with ethanol and saline, and the decreased contents of coenzymes Q9 and Q10 were slightly restored by this treatment. This enzyme activity was also significantly recovered by an intravenous administration of BCG, and was elevated more by the combined treatment with BCG and the emulsified coenzyme Q10. These results suggest that the combined treatment with BCG and emulsified coenzyme Q10 can contribute to the improvement of the depressed bioenergetics in lymphocytes of tumor-bearing animals, and that this combined effect of BCG and emulsified coenzyme Q10 might be based on the combination of their individual activating effect on lymphocytes.", "contents": "Combined effect of BCG and coenzyme Q10 on ATP-ase activity and coenzyme Q content in spleen lymphocytes of tumor-bearing rats. Effect of BCG, coenzyme Q10, or their combination on ATPase activity in spleen lymphocytes of tumor-bearing rats was investigated in relation to changes in the content of individual coenzyme Q homologs in these cells. Contents of both coenzyme Q9 and Q10 in spleen lymphocytes significantly decreased in the late stage of Donryu rats bearing Sato lung carcinoma. Oligomycin-sensitive ATPase activity in spleen lymphocytes was also significantly depressed in this stage. The depressed, oligomycin-sensitive ATPase activity was significantly recovered by a 3-time intramuscular administration of coenzyme Q10 emulsified with ethanol and saline, and the decreased contents of coenzymes Q9 and Q10 were slightly restored by this treatment. This enzyme activity was also significantly recovered by an intravenous administration of BCG, and was elevated more by the combined treatment with BCG and the emulsified coenzyme Q10. These results suggest that the combined treatment with BCG and emulsified coenzyme Q10 can contribute to the improvement of the depressed bioenergetics in lymphocytes of tumor-bearing animals, and that this combined effect of BCG and emulsified coenzyme Q10 might be based on the combination of their individual activating effect on lymphocytes."} {"id": "PMID:157310", "title": "Blastogenic response of spleen cells from C1300 neuroblastoma-bearing mice to tumor cells or soluble and insoluble tumor antigens.", "content": "Adult A/J mice inoculated with 1 x 10(6) syngeneic C1300 neuroblastoma cells had a palpable tumor after 1 week, and the tumor grew uniformly. The hypertonic KCl extract of the tumor induced blastogenic response of syngeneic spleen cells from tumor-bearing mice, and tumor antigens were considered to be solubilized by KCl from tumor cells. Although a higher blastogenic response to insoluble tumor antigens coupled to Sepharose 4B beads could have been expected as demonstrated in this mixed lymphocyte-tumor cell reaction (MLTR) assays, the blastogenic activity, which was approximately equal to that of soluble tumor antigens, was less than one-third of that in MLTR. The initial information of blastogenic response was found to be transmitted to the responder cells with out the entrance of tumor antigens into the cells by the use of insoluble tumor antigens. Blastogenic responses to soluble tumor antigens and to irradiated tumor cells (MLTR) in spleen cells from tumor-bearing mice were serially assayed after tumor inoculation. The response to soluble tumor antigens reached a peak 2 weeks after inoculation but a progressive depression of the responses was observed after a marked tumor growth. Although the blastogenic activity of soluble tumor antigens was small, changes in consecutive response to soluble tumor antigens in tumor-bearing mice were well correlated with those in MLTR. The blastogenic responses to soluble tumor antigens and MLTR were considered to be the manifestation of tumor-specific cell-mediated immunity. Furthermore, the serial blastogenic responses to concanavalin-A and lipopolysaccharide were also coincident with those of tumor-specific immunity.", "contents": "Blastogenic response of spleen cells from C1300 neuroblastoma-bearing mice to tumor cells or soluble and insoluble tumor antigens. Adult A/J mice inoculated with 1 x 10(6) syngeneic C1300 neuroblastoma cells had a palpable tumor after 1 week, and the tumor grew uniformly. The hypertonic KCl extract of the tumor induced blastogenic response of syngeneic spleen cells from tumor-bearing mice, and tumor antigens were considered to be solubilized by KCl from tumor cells. Although a higher blastogenic response to insoluble tumor antigens coupled to Sepharose 4B beads could have been expected as demonstrated in this mixed lymphocyte-tumor cell reaction (MLTR) assays, the blastogenic activity, which was approximately equal to that of soluble tumor antigens, was less than one-third of that in MLTR. The initial information of blastogenic response was found to be transmitted to the responder cells with out the entrance of tumor antigens into the cells by the use of insoluble tumor antigens. Blastogenic responses to soluble tumor antigens and to irradiated tumor cells (MLTR) in spleen cells from tumor-bearing mice were serially assayed after tumor inoculation. The response to soluble tumor antigens reached a peak 2 weeks after inoculation but a progressive depression of the responses was observed after a marked tumor growth. Although the blastogenic activity of soluble tumor antigens was small, changes in consecutive response to soluble tumor antigens in tumor-bearing mice were well correlated with those in MLTR. The blastogenic responses to soluble tumor antigens and MLTR were considered to be the manifestation of tumor-specific cell-mediated immunity. Furthermore, the serial blastogenic responses to concanavalin-A and lipopolysaccharide were also coincident with those of tumor-specific immunity."} {"id": "PMID:157311", "title": "[Statistical survey on laparoscopy in gynaecology up to 1977 in the Federal Republic of Germany (author's transl)].", "content": "1385 questionaires were sent to gynaecologists in West Germany. 682 (49.2%) were answered anonymously. 302 answers (44.2%) revealed that the gynaecologists did not do endoscopy. 265.900 pelviscopies or laparoscopies were included in the statistics. The laparoscopies or pelviscopies were done from 1949--1977 by 380 gynaecologic surgeons or gynaecological departments. In Germany to the end of 1977 unipolar high frequency current was used for hemostasis in 52%, bipolar high frequency current in 42%, and modern endocoaglation in 25% of the departments. In 240 departments (63%) the five to 8 mm. pelviscope was used. In 124 department (33%) the 11 mm. laparoscope was used. In the total of the cases 949 (3.56/1000) complications occurred. These required 690 laparotomies (2.59/1000). The cause of the complications were injuries to vessels or high frequency current burns. A total of 24 (0.09/1000) deaths or 1 death per 11,000 pelviscopies was reported. The operative mortality was 13 deaths (0.09/1000) in 140,977 (53%) purely diagnostic pelviscopies or laparoscopies, 3 deaths (0.08/1000) in 37,639 (14.2%) combined diagnostic and operative pelviscopies and 8 deaths (0.09/1000) in 87,284 (32.8%) laparoscopic tubal ligations. Since 1974 the operative mortality is less than 1:100,000. Since 1973 approximately 30--35,000 pelviscopies are done yearly in West Germany.", "contents": "[Statistical survey on laparoscopy in gynaecology up to 1977 in the Federal Republic of Germany (author's transl)]. 1385 questionaires were sent to gynaecologists in West Germany. 682 (49.2%) were answered anonymously. 302 answers (44.2%) revealed that the gynaecologists did not do endoscopy. 265.900 pelviscopies or laparoscopies were included in the statistics. The laparoscopies or pelviscopies were done from 1949--1977 by 380 gynaecologic surgeons or gynaecological departments. In Germany to the end of 1977 unipolar high frequency current was used for hemostasis in 52%, bipolar high frequency current in 42%, and modern endocoaglation in 25% of the departments. In 240 departments (63%) the five to 8 mm. pelviscope was used. In 124 department (33%) the 11 mm. laparoscope was used. In the total of the cases 949 (3.56/1000) complications occurred. These required 690 laparotomies (2.59/1000). The cause of the complications were injuries to vessels or high frequency current burns. A total of 24 (0.09/1000) deaths or 1 death per 11,000 pelviscopies was reported. The operative mortality was 13 deaths (0.09/1000) in 140,977 (53%) purely diagnostic pelviscopies or laparoscopies, 3 deaths (0.08/1000) in 37,639 (14.2%) combined diagnostic and operative pelviscopies and 8 deaths (0.09/1000) in 87,284 (32.8%) laparoscopic tubal ligations. Since 1974 the operative mortality is less than 1:100,000. Since 1973 approximately 30--35,000 pelviscopies are done yearly in West Germany."} {"id": "PMID:157317", "title": "Steroid metabolism in vitro by gonadal tissue from a true hermaphrodite.", "content": "The case of a true hermaphrodite, with a normal ovary and an ovotestis is presented. The ovotestis was removed and incubated in vitro with tritiated steroids (testosterone, dehydroepiandrosterone, pregnenolone and 17 alpha-hydroxyprogesterone). Labeled metabolites were isolated and identified. Based upon these findings, a pathway of steroid biogenesis in this abnormal gonadal tissue is suggested. The ovotestis studied did not contain all the enzymes involved in ovarian steroidogenesis: 3 beta-hydroxysteroid dehydrogenase, isomerase, 17--20 desmolase and 17 beta-hydroxysteroid dehydrogenase were present, but other important enzymes, such as 16 and 17-hydroxylases, and aromatizing enzyme systems, were deficient or absent.", "contents": "Steroid metabolism in vitro by gonadal tissue from a true hermaphrodite. The case of a true hermaphrodite, with a normal ovary and an ovotestis is presented. The ovotestis was removed and incubated in vitro with tritiated steroids (testosterone, dehydroepiandrosterone, pregnenolone and 17 alpha-hydroxyprogesterone). Labeled metabolites were isolated and identified. Based upon these findings, a pathway of steroid biogenesis in this abnormal gonadal tissue is suggested. The ovotestis studied did not contain all the enzymes involved in ovarian steroidogenesis: 3 beta-hydroxysteroid dehydrogenase, isomerase, 17--20 desmolase and 17 beta-hydroxysteroid dehydrogenase were present, but other important enzymes, such as 16 and 17-hydroxylases, and aromatizing enzyme systems, were deficient or absent."} {"id": "PMID:157318", "title": "Screening for specific calf thymus inhibitors (chalones) of T-lymphocyte proliferation.", "content": "Using agar colony assays with truly proliferating stimulated human T-lymphocytes and mouse granulocytes, two ultrafiltrate fractions were obtained from calf thymus which preferentially inhibited lymphocyte colony growth: Fraction I in the molecular range 1000-10,000 proved to be stable upon heating, prolonged storage and lyophilization, whereas Fraction II in the molecular range 10,000-30,000, was found to be unstable. Fraction I was also extracted with Tween 80 and cetyltrimethylammonium bromide. Chromatography of Fraction I on Biogel P6 and DEAE-cellulose further increased its specificity of inhibition for lymphocyte colony growth and revealed an estimated molecular weight of below 1400. Its inhibitory activity was found to be reversible and unlikely to result from spermine. Thus the properties of fraction I meet the requirements of a T-lymphocyte chalone as an endogenous non-cytotoxic and reversible inhibitor of T-lymphocyte proliferation.", "contents": "Screening for specific calf thymus inhibitors (chalones) of T-lymphocyte proliferation. Using agar colony assays with truly proliferating stimulated human T-lymphocytes and mouse granulocytes, two ultrafiltrate fractions were obtained from calf thymus which preferentially inhibited lymphocyte colony growth: Fraction I in the molecular range 1000-10,000 proved to be stable upon heating, prolonged storage and lyophilization, whereas Fraction II in the molecular range 10,000-30,000, was found to be unstable. Fraction I was also extracted with Tween 80 and cetyltrimethylammonium bromide. Chromatography of Fraction I on Biogel P6 and DEAE-cellulose further increased its specificity of inhibition for lymphocyte colony growth and revealed an estimated molecular weight of below 1400. Its inhibitory activity was found to be reversible and unlikely to result from spermine. Thus the properties of fraction I meet the requirements of a T-lymphocyte chalone as an endogenous non-cytotoxic and reversible inhibitor of T-lymphocyte proliferation."} {"id": "PMID:157320", "title": "The special ministry in long term care.", "content": "Ministers to mentally ill, chemically dependent, physically handicapped, elderly, or retarded persons in long term care must examine their own prejudices, guilt, fears, and pain. Only then can they see each patient as an individual who must be brought to self-love.", "contents": "The special ministry in long term care. Ministers to mentally ill, chemically dependent, physically handicapped, elderly, or retarded persons in long term care must examine their own prejudices, guilt, fears, and pain. Only then can they see each patient as an individual who must be brought to self-love."} {"id": "PMID:157321", "title": "Recurrence of Down's syndrome associated with microchromosome.", "content": "We report a family with five members presenting an extra bisatellited microchromosome. Two of them also present trisomy 21. We discuss the relationship between trisomy and the extra chromosome.", "contents": "Recurrence of Down's syndrome associated with microchromosome. We report a family with five members presenting an extra bisatellited microchromosome. Two of them also present trisomy 21. We discuss the relationship between trisomy and the extra chromosome."} {"id": "PMID:157324", "title": "Species restriction of the mitogenicity induced by lanatoside C. Lymphocyte activation by digitalis glycosides is confined to cells from digitalis resistant species.", "content": "Activation of Na+, K+-ATPase has previously been suggested to be the triggering signal in mitogen-induced cell activation. Using a digitalis glycoside known to be a potent polyclonal B-cell activator, this hypothesis could be tested since digitalis activates ATPase at different concentrations in various species, depending on the degree of sensitivity to the toxic effects of glycosides. Lanatoside C was found to stimulate lymphocytes from glycoside resistant species such as rat, mouse and hamster. The possible involvement of Na+, K+-ATPase was made less likely by the similarity in dose--response profile in these cells although they have been reported to display varying degrees of glycoside resistance. Furthermore, using lymphocytes from digitalis-sensitive species such as man, guinea-pig or rabbit, no mitogenicity could be recorded, strongly suggesting a lack of correlation between glycoside-induced effects on Na+, K+-ATPase and cell activation.", "contents": "Species restriction of the mitogenicity induced by lanatoside C. Lymphocyte activation by digitalis glycosides is confined to cells from digitalis resistant species. Activation of Na+, K+-ATPase has previously been suggested to be the triggering signal in mitogen-induced cell activation. Using a digitalis glycoside known to be a potent polyclonal B-cell activator, this hypothesis could be tested since digitalis activates ATPase at different concentrations in various species, depending on the degree of sensitivity to the toxic effects of glycosides. Lanatoside C was found to stimulate lymphocytes from glycoside resistant species such as rat, mouse and hamster. The possible involvement of Na+, K+-ATPase was made less likely by the similarity in dose--response profile in these cells although they have been reported to display varying degrees of glycoside resistance. Furthermore, using lymphocytes from digitalis-sensitive species such as man, guinea-pig or rabbit, no mitogenicity could be recorded, strongly suggesting a lack of correlation between glycoside-induced effects on Na+, K+-ATPase and cell activation."} {"id": "PMID:157337", "title": "The human dura mater valve. Fabrication methods.", "content": "We have used a glycerol-treated human dura mater valve as a valve substitute of the blood pumps for more than 3 years. In comparative studies, it was shown that the dura mater valve is more durable than the glutaraldehyde-treated bovine aortic valves, and thought to be a very attractive valve material. Fabrication methods both for rigid and flexible stents were introduced.", "contents": "The human dura mater valve. Fabrication methods. We have used a glycerol-treated human dura mater valve as a valve substitute of the blood pumps for more than 3 years. In comparative studies, it was shown that the dura mater valve is more durable than the glutaraldehyde-treated bovine aortic valves, and thought to be a very attractive valve material. Fabrication methods both for rigid and flexible stents were introduced."} {"id": "PMID:157338", "title": "Clinical pharmacology of a combination of bronchodilators.", "content": "27 hospitalized patients (15 suffering from chronic bronchitis with evident bronchospasm and 12 with extrinsic asthma) were evaluated with regard to the bronchodilating effects of a Salbutamol + Ipratropium Bromide combination administered by aerosol. For comparison, the bronchial spasmolytic effectiveness of both drugs administered separately at therapeutic doses was also evaluated. Subsequently, the activity of increasing doses of the combination was studied, with particular regard to possible side-effects. The pharmacological combination studied exerted a strong bronchodilating activity, independently of dose increase, both in asthmatic and in bronchitic patients. No side-effects were observed.", "contents": "Clinical pharmacology of a combination of bronchodilators. 27 hospitalized patients (15 suffering from chronic bronchitis with evident bronchospasm and 12 with extrinsic asthma) were evaluated with regard to the bronchodilating effects of a Salbutamol + Ipratropium Bromide combination administered by aerosol. For comparison, the bronchial spasmolytic effectiveness of both drugs administered separately at therapeutic doses was also evaluated. Subsequently, the activity of increasing doses of the combination was studied, with particular regard to possible side-effects. The pharmacological combination studied exerted a strong bronchodilating activity, independently of dose increase, both in asthmatic and in bronchitic patients. No side-effects were observed."} {"id": "PMID:157340", "title": "Plasma testosterone levels before and after stimulation with HCG in anorchism.", "content": "The authors present four cases of operatively confirmed anorchism. The plasma levels of testosterone and 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine were low in all cases. After stimulation with HCG, plasma testosterone levels increased in two cases and did not change in another two. The levels of 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine did not increase.", "contents": "Plasma testosterone levels before and after stimulation with HCG in anorchism. The authors present four cases of operatively confirmed anorchism. The plasma levels of testosterone and 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine were low in all cases. After stimulation with HCG, plasma testosterone levels increased in two cases and did not change in another two. The levels of 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine did not increase."} {"id": "PMID:157341", "title": "Experimental glomerular lesions induced by chronic immune complex formation. I. Formation and elimination of the immune complex (relationship between the immune status and the glomerular changes).", "content": "Chronic immune complex formation was induced in rabbits by daily administration of 12.5 g bovine serum. In good antibody producer animals immediate immune complex production and elimination from the circulation were demonstrable. This was followed within a few minutes by the appearance of free 125I in fairly large amounts in blood, as a sign of immediate phagocytosis and disintegration of the 125I-labelled immune complexes. Phagocytic activity decreased in the host animal during chronic heteroprotein administration in every case. The earliest glomerular changes were those of exudative glomerulonephritis, the extent of which depended on the antibody productivity of the animal. Persistent immunocomplexaemia induced by administration of the antigen over 60 and 100 days, respectively, resulted in mesangioproliferative glomerulonephritis in 7, in membranoproliferative glomerulonephritis in 3, and in membraneous glomerulonephritis in 1 out of 11 laboratory animals.", "contents": "Experimental glomerular lesions induced by chronic immune complex formation. I. Formation and elimination of the immune complex (relationship between the immune status and the glomerular changes). Chronic immune complex formation was induced in rabbits by daily administration of 12.5 g bovine serum. In good antibody producer animals immediate immune complex production and elimination from the circulation were demonstrable. This was followed within a few minutes by the appearance of free 125I in fairly large amounts in blood, as a sign of immediate phagocytosis and disintegration of the 125I-labelled immune complexes. Phagocytic activity decreased in the host animal during chronic heteroprotein administration in every case. The earliest glomerular changes were those of exudative glomerulonephritis, the extent of which depended on the antibody productivity of the animal. Persistent immunocomplexaemia induced by administration of the antigen over 60 and 100 days, respectively, resulted in mesangioproliferative glomerulonephritis in 7, in membranoproliferative glomerulonephritis in 3, and in membraneous glomerulonephritis in 1 out of 11 laboratory animals."} {"id": "PMID:157342", "title": "Experimental glomerular lesions induced by chronic immune complex formation. II. Pathomorphological analysis.", "content": "Eleven rabbits were given bovine serum albumin i.v., in daily doses of 25 mg. Renal biopsy was performed on the 30th, 60th and 100th day of treatment and the specimens were subjected to light-, electron-microscopic and immunofluorescent studies, so as to follow up the dynamics of the glomerular process. Proteinuria and the serum creatinine and BUN levels were also measured. By the 100th day of treatment mesangioproliferative glomerulopathy had developed in 7, membranoproliferative glomerulopathy in 3 cases and membraneous glomerulopathy in 1 case. On the 30th day of treatment exudative glomerulopathy was demonstrable in the majority of the cases (in 9 animals). It is suggested that the earliest stage of the various glomerulopathies, regardless of their type, is marked by exudative lesions. The heaviest proteinuria was found in membraneous and membranoproliferative glomerulopathies. Changes in the serum creatinine and BUN levels indicative of a deteriorating renal function were noted in the membranoproliferative cases. The results are correlated with clinical observations of human glomerulopathies.", "contents": "Experimental glomerular lesions induced by chronic immune complex formation. II. Pathomorphological analysis. Eleven rabbits were given bovine serum albumin i.v., in daily doses of 25 mg. Renal biopsy was performed on the 30th, 60th and 100th day of treatment and the specimens were subjected to light-, electron-microscopic and immunofluorescent studies, so as to follow up the dynamics of the glomerular process. Proteinuria and the serum creatinine and BUN levels were also measured. By the 100th day of treatment mesangioproliferative glomerulopathy had developed in 7, membranoproliferative glomerulopathy in 3 cases and membraneous glomerulopathy in 1 case. On the 30th day of treatment exudative glomerulopathy was demonstrable in the majority of the cases (in 9 animals). It is suggested that the earliest stage of the various glomerulopathies, regardless of their type, is marked by exudative lesions. The heaviest proteinuria was found in membraneous and membranoproliferative glomerulopathies. Changes in the serum creatinine and BUN levels indicative of a deteriorating renal function were noted in the membranoproliferative cases. The results are correlated with clinical observations of human glomerulopathies."} {"id": "PMID:157343", "title": "[Early scanning electron microscopy changes in the surface of woven dacron vessel prosthesis. An experimental study in dogs].", "content": "To evaluate platelet-inhibiting drugs in vivo, we implanted artificial vessels into the arterial blood-stream of dogs. Following different periods of normal blood-flow through the prosthesis, pieces were cut out and prepared for scanning electron microscopy (SEM). Through the SEM we studied surface changes of the samples, in particular those of platelets. They very soon loose their disclike form becoming relatively spherical and make contact with each other by means of pseudopods that are formed at that stage. Red blood cells are caught up in this 3-dimensional network causing the inner surface of the dacron prosthesis to look like an underwatergarden.", "contents": "[Early scanning electron microscopy changes in the surface of woven dacron vessel prosthesis. An experimental study in dogs]. To evaluate platelet-inhibiting drugs in vivo, we implanted artificial vessels into the arterial blood-stream of dogs. Following different periods of normal blood-flow through the prosthesis, pieces were cut out and prepared for scanning electron microscopy (SEM). Through the SEM we studied surface changes of the samples, in particular those of platelets. They very soon loose their disclike form becoming relatively spherical and make contact with each other by means of pseudopods that are formed at that stage. Red blood cells are caught up in this 3-dimensional network causing the inner surface of the dacron prosthesis to look like an underwatergarden."} {"id": "PMID:157344", "title": "The structure and source of lingual proprioceptors in the monkey.", "content": "The proprioceptive innervation of the tounge has been investigated in the Cynamolgus monkey by silver impregnation methods following unilateral section of lingual, hypoglossal, and cervical nerves. Muscle spindles were constantly present in the intrinsic and extrinsic muscles. They varied greatly in number, averaged half the length of lumbrical spindles, and showed an unusual arrangement of chain fibre nuclei. Other, inconstant proprioceptors included tendon endings, Ruffini endings, Pacinian corpuscles, paciniform and lamellated endings. Topologically, the endings other than spindles were extra-muscular, so that the overall pattern of proprioceptive innervation resembled that of skeletal muscle in general. Lingual nerve section was without apparent effect on the proprioceptors. Section of the hypoglossal nerve at its point of entry into the tongue caused severe depletiion of ipsilateral proprioceptors and of fusimotor nerves. In the anterior tongue there was evidence of transmedian overlap by efferent and afferent axons contained in the hypoglossal nerve. Hypoglossal section at the skull base caused degeneration of fusimotor nerves but not of proprioceptors. Section of (a), the connexion of C2-C3 ventral rami with the hypoglossal, together with section of (b), the ramus descendens hypoglossi, coused depletion of lingual proprioceptors; again there was evidence of transmedian overlap. Procedures (a) or (b) alone had a lesser effect. It was concluded that lingual proprioceptive afferent fibres occupy the distal hypoglossal nerve, leaving it in the ramus descendens and in the C2-C3 connexion to enter the spinal cord via nerves C2 and C3.", "contents": "The structure and source of lingual proprioceptors in the monkey. The proprioceptive innervation of the tounge has been investigated in the Cynamolgus monkey by silver impregnation methods following unilateral section of lingual, hypoglossal, and cervical nerves. Muscle spindles were constantly present in the intrinsic and extrinsic muscles. They varied greatly in number, averaged half the length of lumbrical spindles, and showed an unusual arrangement of chain fibre nuclei. Other, inconstant proprioceptors included tendon endings, Ruffini endings, Pacinian corpuscles, paciniform and lamellated endings. Topologically, the endings other than spindles were extra-muscular, so that the overall pattern of proprioceptive innervation resembled that of skeletal muscle in general. Lingual nerve section was without apparent effect on the proprioceptors. Section of the hypoglossal nerve at its point of entry into the tongue caused severe depletiion of ipsilateral proprioceptors and of fusimotor nerves. In the anterior tongue there was evidence of transmedian overlap by efferent and afferent axons contained in the hypoglossal nerve. Hypoglossal section at the skull base caused degeneration of fusimotor nerves but not of proprioceptors. Section of (a), the connexion of C2-C3 ventral rami with the hypoglossal, together with section of (b), the ramus descendens hypoglossi, coused depletion of lingual proprioceptors; again there was evidence of transmedian overlap. Procedures (a) or (b) alone had a lesser effect. It was concluded that lingual proprioceptive afferent fibres occupy the distal hypoglossal nerve, leaving it in the ramus descendens and in the C2-C3 connexion to enter the spinal cord via nerves C2 and C3."} {"id": "PMID:157345", "title": "Studies on the biosynthesis of the antibiotic streptozotocin (streptozocin) by Streptomyces achromogenes var. streptozoticus. Feeding experiments with carbon-14 and tritium labelled precursors.", "content": "Feeding experiments and chemical degradations have shown that D-[1(-14)C,2(-3)H]-and-[1(-14)C,6(-3)H] glucosamine, L-[ureido-14C] citrulline, L-[guanidino-14C] arginine and L-[14CH3] methionine specifically label the glucosamine moiety, the urea carbonyl and the N-methyl group of the antibiotic streptozotocin, respectively. Feeding these precursors in amounts of 5 approximately 10 mumoles per 100 ml of culture medium under conditions where the fermentation yielded approximately 20 mumoles of streptozotocin in 24 hours gave incorporation rates which approached 40%. Upon feeding 100 mumoles of either D-[1(-14)C] glucosamine or L-[ureido-14C] citrulline they were incorporated into newly synthesized streptozotocin essentially without dilution by endogeneous precursors. D-[1(-14)C, 6(-3)H] Glucosamine was incorporated without change in T/C ratio while 20% of the tritium was lost from D-[1(-14)C,2(-3)H] glucosamine, suggesting the possibility that D-glucosamine can partially equilibrate with D-fructose prior to its incorporation.", "contents": "Studies on the biosynthesis of the antibiotic streptozotocin (streptozocin) by Streptomyces achromogenes var. streptozoticus. Feeding experiments with carbon-14 and tritium labelled precursors. Feeding experiments and chemical degradations have shown that D-[1(-14)C,2(-3)H]-and-[1(-14)C,6(-3)H] glucosamine, L-[ureido-14C] citrulline, L-[guanidino-14C] arginine and L-[14CH3] methionine specifically label the glucosamine moiety, the urea carbonyl and the N-methyl group of the antibiotic streptozotocin, respectively. Feeding these precursors in amounts of 5 approximately 10 mumoles per 100 ml of culture medium under conditions where the fermentation yielded approximately 20 mumoles of streptozotocin in 24 hours gave incorporation rates which approached 40%. Upon feeding 100 mumoles of either D-[1(-14)C] glucosamine or L-[ureido-14C] citrulline they were incorporated into newly synthesized streptozotocin essentially without dilution by endogeneous precursors. D-[1(-14)C, 6(-3)H] Glucosamine was incorporated without change in T/C ratio while 20% of the tritium was lost from D-[1(-14)C,2(-3)H] glucosamine, suggesting the possibility that D-glucosamine can partially equilibrate with D-fructose prior to its incorporation."} {"id": "PMID:157353", "title": "Structure of cross-linked rabbit muscle phosphofructokinase in solution.", "content": "Cross-linked rabbit muscle phosphofructokinase in the active tetrameric and octameric state was studied in solution by hydrodynamic methods and small angle x-ray scattering techniques. The translational diffusion coefficients were determined by means of inelastic light scattering and were found to be 3.60 (+/- 0.02) x 10(-7) cm2 . s-1 for the tetramer and 2.54 (+/- 0.15) x 10(-7) cm2 . s-1 for the octamer. From small angle x-ray scattering measurements the radius of gyration, the specific inner surface area, and the volume were determined for both enzyme forms, revealing that the octameric cross-linked form is approximately spherical, with a diameter of 120.0 A, whereas the tetrameric form is asymmetric having an axial ratio of 2. By comparison of the scattering curves with triaxial geometric bodies which are equivalent in scattering, the tetrameric enzyme is described as a rectangular prism, with overall dimensions of A = 131.0 A, B = 131.0 A, and C = 65.0 A, and the octameric form as that of a cube with A = B = C = 120.0 A. The shape of the protomer, having a radius of gyration of 24.8 A, in the tetramer and octamer is similar to that for the native tetramer at pH 10 in the presence of 5 mM fructose 6-phosphate or 15 mM fructose 1,6-bis-phosphate. From the different shapes of the scattering curves of the native phosphofructokinase at pH 7.5 in the presence of 15 mM ATP and of the cross-linked tetramer or octamer, it can be inferred that the shapes of the protomers are different: in the presence of ATP the protomers are elongated, having an axial ratio of 1.8 to 2.0; the cross-linked state reveals a spherical protomer of radius 33.0 A, similar to that of the native enzyme at pH 7.5 in the presence of fructose 6-phosphate or fructose 1,6-bisphosphate.", "contents": "Structure of cross-linked rabbit muscle phosphofructokinase in solution. Cross-linked rabbit muscle phosphofructokinase in the active tetrameric and octameric state was studied in solution by hydrodynamic methods and small angle x-ray scattering techniques. The translational diffusion coefficients were determined by means of inelastic light scattering and were found to be 3.60 (+/- 0.02) x 10(-7) cm2 . s-1 for the tetramer and 2.54 (+/- 0.15) x 10(-7) cm2 . s-1 for the octamer. From small angle x-ray scattering measurements the radius of gyration, the specific inner surface area, and the volume were determined for both enzyme forms, revealing that the octameric cross-linked form is approximately spherical, with a diameter of 120.0 A, whereas the tetrameric form is asymmetric having an axial ratio of 2. By comparison of the scattering curves with triaxial geometric bodies which are equivalent in scattering, the tetrameric enzyme is described as a rectangular prism, with overall dimensions of A = 131.0 A, B = 131.0 A, and C = 65.0 A, and the octameric form as that of a cube with A = B = C = 120.0 A. The shape of the protomer, having a radius of gyration of 24.8 A, in the tetramer and octamer is similar to that for the native tetramer at pH 10 in the presence of 5 mM fructose 6-phosphate or 15 mM fructose 1,6-bis-phosphate. From the different shapes of the scattering curves of the native phosphofructokinase at pH 7.5 in the presence of 15 mM ATP and of the cross-linked tetramer or octamer, it can be inferred that the shapes of the protomers are different: in the presence of ATP the protomers are elongated, having an axial ratio of 1.8 to 2.0; the cross-linked state reveals a spherical protomer of radius 33.0 A, similar to that of the native enzyme at pH 7.5 in the presence of fructose 6-phosphate or fructose 1,6-bisphosphate."} {"id": "PMID:157356", "title": "Human erythrocyte calmodulin. Further chemical characterization and the site of its interaction with the membrane.", "content": "Human erythrocyte and bovine brain calmodulins were indistinguishable by tryptic peptide mapping, indicating that the primary sequence of the two proteins is either very similar or identical. Calcium binding determinations of human erythrocyte calmodulin, by equilibrium dialysis and fluorescence titration, were in close agreement with previous studies on other calmodulins. The calcium-activated adenosine triphosphatase which is stimulated by calmodulin was shown to be firmly associated with smooth erythrocyte plasma membranes devoid of spectrin and actin. Kinetic titration demonstrated that there are 4500 calmodulin binding sites per erythrocyte and that the turnover number of this calcium-activated adenosine triphosphatase is 3000 mumol of Pi . (mumol of site)-1 . min-1 which is similar to the turnover numbers of other transport adenosine triphosphatases. Furthermore, calmodulin stimulates calcium-activated adenosine triphosphatase by a simple enzyme-ligand association.", "contents": "Human erythrocyte calmodulin. Further chemical characterization and the site of its interaction with the membrane. Human erythrocyte and bovine brain calmodulins were indistinguishable by tryptic peptide mapping, indicating that the primary sequence of the two proteins is either very similar or identical. Calcium binding determinations of human erythrocyte calmodulin, by equilibrium dialysis and fluorescence titration, were in close agreement with previous studies on other calmodulins. The calcium-activated adenosine triphosphatase which is stimulated by calmodulin was shown to be firmly associated with smooth erythrocyte plasma membranes devoid of spectrin and actin. Kinetic titration demonstrated that there are 4500 calmodulin binding sites per erythrocyte and that the turnover number of this calcium-activated adenosine triphosphatase is 3000 mumol of Pi . (mumol of site)-1 . min-1 which is similar to the turnover numbers of other transport adenosine triphosphatases. Furthermore, calmodulin stimulates calcium-activated adenosine triphosphatase by a simple enzyme-ligand association."} {"id": "PMID:157357", "title": "Cell-surface heparan sulfate. Isolation and characterization of a proteoglycan from rat liver membranes.", "content": "Solubilization of heparan sulfate proteoglycans from a rat liver membrane fraction was obtained by the use of the charged detergent deoxycholate or alternatively a combination of NaCl and the nonionic detergent Triton-X 100. Subsequently, proteoglycans solubilized from microsomal and plasma membrane fractions, respectively, were purified by a procedure involving gel chromatography, anion exchange chromatography, and density gradient centrifugation. The purified heparan sulfate proteoglycan had a molecular weight of about 75,000 as determined by sedimentation equilibrium analysis or gel chromatography. Molecular weights of 17,000 to 40,000 were obtained for the 125I-labeled core protein after removal of the heparan sulfate polysaccharide chains by different enzymatic and chemical methods. An average molecular weight of 14,000 was found for the polysaccharide chains released from the core protein by alkali treatment. The data are consistent with a proteoglycan structure containing four polysaccharide chains attached to the core protein. The amino acid composition of native and alkali-treated proteoglycan support the proposed proteoglycan model.", "contents": "Cell-surface heparan sulfate. Isolation and characterization of a proteoglycan from rat liver membranes. Solubilization of heparan sulfate proteoglycans from a rat liver membrane fraction was obtained by the use of the charged detergent deoxycholate or alternatively a combination of NaCl and the nonionic detergent Triton-X 100. Subsequently, proteoglycans solubilized from microsomal and plasma membrane fractions, respectively, were purified by a procedure involving gel chromatography, anion exchange chromatography, and density gradient centrifugation. The purified heparan sulfate proteoglycan had a molecular weight of about 75,000 as determined by sedimentation equilibrium analysis or gel chromatography. Molecular weights of 17,000 to 40,000 were obtained for the 125I-labeled core protein after removal of the heparan sulfate polysaccharide chains by different enzymatic and chemical methods. An average molecular weight of 14,000 was found for the polysaccharide chains released from the core protein by alkali treatment. The data are consistent with a proteoglycan structure containing four polysaccharide chains attached to the core protein. The amino acid composition of native and alkali-treated proteoglycan support the proposed proteoglycan model."} {"id": "PMID:157359", "title": "Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver.", "content": "[1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver.", "contents": "Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver. [1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver."} {"id": "PMID:157360", "title": "Intraamniotic or intravenous injection of dehydroepiandrosterone sulfate in midgestation: effect on prolactin level in maternal serum and amniotic fluid.", "content": "The influence of dehydroepiandrosterone sulfate (DHEA-S) on PRL levels in maternal serum and amniotic fluid at midgestation was evaluated in a series of 32 women admitted for midtrimester abortion. Serum was collected hourly for 6 h in 13 women after intraamniotic (ia) instillation (100--200 mg) or in 10 women after iv injection (100 mg) of DHEA-S, and in 9 control women. Serum PRL levels rose significantly (P less than 0.05) 3--6 h after ia and 2--6 h after iv administration of DHEA-S but was unchanged in the control group. The elevation of serum PRL levels is most likely secondary to increased levels of serum estrogens which accompany ia or iv administration of DHEA-S. This suggests that maternal pituitary PRL secretion is responsive to additional stimulation by endogenous estrogens at midgestation. The amniotic fluid PRL level ranged from 1109-2473 ng/ml, with no consistent change after administration of ia DHEA-S, intimating that estrogens may not be implicated in the control of PRL in amniotic fluid.", "contents": "Intraamniotic or intravenous injection of dehydroepiandrosterone sulfate in midgestation: effect on prolactin level in maternal serum and amniotic fluid. The influence of dehydroepiandrosterone sulfate (DHEA-S) on PRL levels in maternal serum and amniotic fluid at midgestation was evaluated in a series of 32 women admitted for midtrimester abortion. Serum was collected hourly for 6 h in 13 women after intraamniotic (ia) instillation (100--200 mg) or in 10 women after iv injection (100 mg) of DHEA-S, and in 9 control women. Serum PRL levels rose significantly (P less than 0.05) 3--6 h after ia and 2--6 h after iv administration of DHEA-S but was unchanged in the control group. The elevation of serum PRL levels is most likely secondary to increased levels of serum estrogens which accompany ia or iv administration of DHEA-S. This suggests that maternal pituitary PRL secretion is responsive to additional stimulation by endogenous estrogens at midgestation. The amniotic fluid PRL level ranged from 1109-2473 ng/ml, with no consistent change after administration of ia DHEA-S, intimating that estrogens may not be implicated in the control of PRL in amniotic fluid."} {"id": "PMID:157362", "title": "Primary leiomyosarcoma of skin: a report and critical appraisal.", "content": "A primary leiomyosarcoma of skin was studied by light and electron microscopy and by histochemistry. Systematic evaluation of the entire neoplasm suggested that a single biopsy sample would show little cellular pleomorphism but could vary considerably in number of mitoses per mm2. Electron microscopy revealed a high degree of cytologic differentiation. Strong myosin ATPase activity and negative demonstrations for hydrolytic enzymes suggest a diagnostic profile which will clearly separate this neoplasm from malignant fibrous histiocytoma. High mitoses counts, the conventional criterion for malignancy of non-cutaneous smooth muscle tumors, may not be appropriately applied to primary leiomyosarcomas arising in the dermis. The findings in this case and a critical review of the literature suggest that reliable criteria for diagnosis of primary cutaneous leiomyosarcoma by light microscopy remain to be established.", "contents": "Primary leiomyosarcoma of skin: a report and critical appraisal. A primary leiomyosarcoma of skin was studied by light and electron microscopy and by histochemistry. Systematic evaluation of the entire neoplasm suggested that a single biopsy sample would show little cellular pleomorphism but could vary considerably in number of mitoses per mm2. Electron microscopy revealed a high degree of cytologic differentiation. Strong myosin ATPase activity and negative demonstrations for hydrolytic enzymes suggest a diagnostic profile which will clearly separate this neoplasm from malignant fibrous histiocytoma. High mitoses counts, the conventional criterion for malignancy of non-cutaneous smooth muscle tumors, may not be appropriately applied to primary leiomyosarcomas arising in the dermis. The findings in this case and a critical review of the literature suggest that reliable criteria for diagnosis of primary cutaneous leiomyosarcoma by light microscopy remain to be established."} {"id": "PMID:157363", "title": "Cobalt induced changes in immune response and adenosine triphosphatase activities in rats.", "content": "The immuno-biochemical effects of cobaltous chloride in rats receiving iron-sufficient and deficient diets were investigated. Rats receiving 100 ppm or more cobalt showed a significant reduction in thymus and body weights along with a marked decrease in hemoglobin, hematocrit, sheep agglutinins and plaque forming cells. These effects were more pronounced in rats receiving cobalt mixed with iron-deficient diet than those fed on iron-sufficient diet. The Na+-K+ and mitochondrial (Oligomycin-sensitive) Mg2+ATPase activities in brain and liver of rats fed with iron-deficient diets were decreased significantly. However, the ATPase activities in these tissues from rats fed with cobalt mixed with iron-sufficient diets were not altered.", "contents": "Cobalt induced changes in immune response and adenosine triphosphatase activities in rats. The immuno-biochemical effects of cobaltous chloride in rats receiving iron-sufficient and deficient diets were investigated. Rats receiving 100 ppm or more cobalt showed a significant reduction in thymus and body weights along with a marked decrease in hemoglobin, hematocrit, sheep agglutinins and plaque forming cells. These effects were more pronounced in rats receiving cobalt mixed with iron-deficient diet than those fed on iron-sufficient diet. The Na+-K+ and mitochondrial (Oligomycin-sensitive) Mg2+ATPase activities in brain and liver of rats fed with iron-deficient diets were decreased significantly. However, the ATPase activities in these tissues from rats fed with cobalt mixed with iron-sufficient diets were not altered."} {"id": "PMID:157364", "title": "Metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) administered topically to a sheep.", "content": "A sheep dosed topically with 14C-crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) excreted 45.5% of the 14C dose in the urine within 9 days. The feces contained 1.2% and the carcass 40.4% (this included the 37.7% of the dose remaining on the skin in the dosing area) of the dose. At sacrifice, the fat, liver, kidney, lung, and skin (where the dose was applied) contained the highest concentrations of 14C. Fourteen urinary metabolites were isolated and characterized by mass spectrometry. The metabolic reactions involved were oxidations of the t-butyl moiety, O-demethylation, replacement of the H-N-CH3 moiety with a hydroxyl group, oxidation of the N-methyl group to yield N-formyl phosphoramidates, hydrolysis of the phosphoramidate moiety to yield phenols, conjugation with glucuronic acid and combinations of these reactions.", "contents": "Metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) administered topically to a sheep. A sheep dosed topically with 14C-crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) excreted 45.5% of the 14C dose in the urine within 9 days. The feces contained 1.2% and the carcass 40.4% (this included the 37.7% of the dose remaining on the skin in the dosing area) of the dose. At sacrifice, the fat, liver, kidney, lung, and skin (where the dose was applied) contained the highest concentrations of 14C. Fourteen urinary metabolites were isolated and characterized by mass spectrometry. The metabolic reactions involved were oxidations of the t-butyl moiety, O-demethylation, replacement of the H-N-CH3 moiety with a hydroxyl group, oxidation of the N-methyl group to yield N-formyl phosphoramidates, hydrolysis of the phosphoramidate moiety to yield phenols, conjugation with glucuronic acid and combinations of these reactions."} {"id": "PMID:157370", "title": "Role of lipids in the immune response. I. Localization to a lipid-containing fraction of the active moiety of an inhibitor (SIF) of lymphocyte proliferation.", "content": "By further study, a previously described inhibitor of lymphocyte proliferation and immunoglobulin synthesis, soluble inhibitory factor (SIF), has been shown to comprise two moieties; a nondialyzable protein, apparently inert with regard to inhibition of proliferation, and a polar lipid bound to the protein fraction, presumably by hydrophobic interaction. The lipid contained the activity responsible for inhibition of PHA-induced DNA synthesis. It was tentatively identified as a lipid with an as yet unidentified polar group, on the basis of mobility on thin layer chromatographic plates and behavior on silicic acid.", "contents": "Role of lipids in the immune response. I. Localization to a lipid-containing fraction of the active moiety of an inhibitor (SIF) of lymphocyte proliferation. By further study, a previously described inhibitor of lymphocyte proliferation and immunoglobulin synthesis, soluble inhibitory factor (SIF), has been shown to comprise two moieties; a nondialyzable protein, apparently inert with regard to inhibition of proliferation, and a polar lipid bound to the protein fraction, presumably by hydrophobic interaction. The lipid contained the activity responsible for inhibition of PHA-induced DNA synthesis. It was tentatively identified as a lipid with an as yet unidentified polar group, on the basis of mobility on thin layer chromatographic plates and behavior on silicic acid."} {"id": "PMID:157375", "title": "The cells involved in cell-mediated and transplantation immunity in the rabbit. XII. The establishment of the optimum conditions for the demonstration of a consistent response for the circulating white blood cells in the mixed leukocyte reaction.", "content": "Rabbit circulating leukocytes (WBC) have been shown to respond consistently in the allogeneic one-way mixed leukocyte culture reaction (MLR). Culture of the cells for 5--6 days in 5% CO2 in air in medium RPMI 1640 supplemented with normal decomplemented rabbit serum to a concentration of 2.5% provided conditions for an optimal MLR response. The WBC of the majority of the normal rabbits tested (82%) responded in the MLR, in contrast to the negative findings of other investigators. The WBC of a minority of the normal rabbits (18%) did not respond in the conventional MLR; however, the spleen cells of these rabbits consistently responded in the MLR, demonstrating that these rabbits possessed MLR responsive cells which may not have been present in the circulation at the time of analysis. Furthermore, the WBC of the 'non-responder' rabbits responded well in the MLR when the allogeneic WBC stimulator cells were replaced by allogenic spleen cells, suggesting that the WBC responder cells require a helper cell provided by the splenic stimulator cells to facilitate the blastogenic response. Whether the MLR responsive cell in the rabbit is a T cell or a 'T-like' cell with B cell properties has still not been resolved.", "contents": "The cells involved in cell-mediated and transplantation immunity in the rabbit. XII. The establishment of the optimum conditions for the demonstration of a consistent response for the circulating white blood cells in the mixed leukocyte reaction. Rabbit circulating leukocytes (WBC) have been shown to respond consistently in the allogeneic one-way mixed leukocyte culture reaction (MLR). Culture of the cells for 5--6 days in 5% CO2 in air in medium RPMI 1640 supplemented with normal decomplemented rabbit serum to a concentration of 2.5% provided conditions for an optimal MLR response. The WBC of the majority of the normal rabbits tested (82%) responded in the MLR, in contrast to the negative findings of other investigators. The WBC of a minority of the normal rabbits (18%) did not respond in the conventional MLR; however, the spleen cells of these rabbits consistently responded in the MLR, demonstrating that these rabbits possessed MLR responsive cells which may not have been present in the circulation at the time of analysis. Furthermore, the WBC of the 'non-responder' rabbits responded well in the MLR when the allogeneic WBC stimulator cells were replaced by allogenic spleen cells, suggesting that the WBC responder cells require a helper cell provided by the splenic stimulator cells to facilitate the blastogenic response. Whether the MLR responsive cell in the rabbit is a T cell or a 'T-like' cell with B cell properties has still not been resolved."} {"id": "PMID:157376", "title": "Mixed lymphocyte reactions in serum-free medium.", "content": "Tissue culture medium supplemented with bovine serum albumin (BSA), rather than human serum, was found capable of supporting the proliferative response of cryopreserved human lymphocytes to allogeneic cells in a one-way mixed lymphocyte culture. Although total tritiated thymidine uptake was lower in BSA supplemented cultures than in serum supplemented cultures, stimulation indices were equivalent. Using 0.5% (w/v) BSA, peak tritiated thymidine uptake was observed on day 5 using 2 X 10(5) responders and 4X 10(5) stimulators per microtitre well. Calf skin gelatin was also found capable of substituting for serum, but gave lower levels of proliferation. Use of BSA offers distinct advantages for investigating the proliferative responses of human lymphocytes in serum-free media.", "contents": "Mixed lymphocyte reactions in serum-free medium. Tissue culture medium supplemented with bovine serum albumin (BSA), rather than human serum, was found capable of supporting the proliferative response of cryopreserved human lymphocytes to allogeneic cells in a one-way mixed lymphocyte culture. Although total tritiated thymidine uptake was lower in BSA supplemented cultures than in serum supplemented cultures, stimulation indices were equivalent. Using 0.5% (w/v) BSA, peak tritiated thymidine uptake was observed on day 5 using 2 X 10(5) responders and 4X 10(5) stimulators per microtitre well. Calf skin gelatin was also found capable of substituting for serum, but gave lower levels of proliferation. Use of BSA offers distinct advantages for investigating the proliferative responses of human lymphocytes in serum-free media."} {"id": "PMID:157383", "title": "Relation of membrane vesicles to volume and Na+ transport in smooth muscle: effect of metabolic and transport inhibition on fresh tissues.", "content": "We tested the hypothesis that membrane vesicles of smooth muscle function as organelles controlling cell volume through a mechanochemical mechanism not involving Na+-K+ dependent membrane ATPase. Pieces of rat myometrium were incubated under various conditions at 25 degrees C, and then were analyzed after various times for Na+, K+, ATP and water contents or were prepared and examined in the electron microscope. Metabolic inhibition with iodoacetate (IAA) + dinitrophenol (DNP) rapidly depleted ATP, then decreased membrane vesicle number and increased vesicle size. Thereafter K+ loss, Na+ gain and water gain occurred. Slower depletion of ATP by treatment of tissues with IAA or ethacrynic acid produced similar, but delayed effects. Treatment with DNP alone, DNP in glucose-free Krebs-Ringer or glucose-free solution bubbled with N2 partly depleted the tissues of ATP but did not markedly affect the membrane vesicles or tissue water content. Ouabain affected neither ATP contents of tissues nor the numberof membrane vesicles, but produced large intracellular vesicles. The membrane vesicles were suggested to be sites of a mechanochemical volume control system.", "contents": "Relation of membrane vesicles to volume and Na+ transport in smooth muscle: effect of metabolic and transport inhibition on fresh tissues. We tested the hypothesis that membrane vesicles of smooth muscle function as organelles controlling cell volume through a mechanochemical mechanism not involving Na+-K+ dependent membrane ATPase. Pieces of rat myometrium were incubated under various conditions at 25 degrees C, and then were analyzed after various times for Na+, K+, ATP and water contents or were prepared and examined in the electron microscope. Metabolic inhibition with iodoacetate (IAA) + dinitrophenol (DNP) rapidly depleted ATP, then decreased membrane vesicle number and increased vesicle size. Thereafter K+ loss, Na+ gain and water gain occurred. Slower depletion of ATP by treatment of tissues with IAA or ethacrynic acid produced similar, but delayed effects. Treatment with DNP alone, DNP in glucose-free Krebs-Ringer or glucose-free solution bubbled with N2 partly depleted the tissues of ATP but did not markedly affect the membrane vesicles or tissue water content. Ouabain affected neither ATP contents of tissues nor the numberof membrane vesicles, but produced large intracellular vesicles. The membrane vesicles were suggested to be sites of a mechanochemical volume control system."} {"id": "PMID:157384", "title": "Relation of membrane vesicles to volume control and Na+-transport in smooth muscle: studies on Na+-rich tissues.", "content": "Correlation between operation of a volume control system (independent of Na+-K+ -ATPase) and membrane vesicle structure was examined in strips of rat myometrium made Na-rich by incubation in Krebs-Ringer solutions at 5 degrees C. Some pieces of tissue were analyzed for Na+, K+, ATP and water contents before and after rewarming to 37 degrees C. Other pieces of tissue were prepared and examined in the electron microscope. The membrane vesicles along the surface of the muscle cells were reduced from the numberin fresh tissues made Na+-rich by overnight incubation in K+-free Ringer solution at 5 degrees C. Rewarming of Na+-rich tissues under conditions thought to inhibit Na+-K+-ATPase caused the loss of Na+ with water and with utake of K+ but the vesicles did not increase in number. Na+-K+ATPase activity was suggested to inhibit vesicle formation by competing for ATP. The loss of water and increase in vesicle number was Ca2+-dependent but did not require Na+. Inhibition of the volume control system by iodoacetamide, Ca2+-free solution and other procedures resulted in swelling of membrane vesicles. The membrane vesicles were suggested to be sites of a mechanochemical system of volume control and the mechanochemical step was suggested to involve discharge of membrane vesicles.", "contents": "Relation of membrane vesicles to volume control and Na+-transport in smooth muscle: studies on Na+-rich tissues. Correlation between operation of a volume control system (independent of Na+-K+ -ATPase) and membrane vesicle structure was examined in strips of rat myometrium made Na-rich by incubation in Krebs-Ringer solutions at 5 degrees C. Some pieces of tissue were analyzed for Na+, K+, ATP and water contents before and after rewarming to 37 degrees C. Other pieces of tissue were prepared and examined in the electron microscope. The membrane vesicles along the surface of the muscle cells were reduced from the numberin fresh tissues made Na+-rich by overnight incubation in K+-free Ringer solution at 5 degrees C. Rewarming of Na+-rich tissues under conditions thought to inhibit Na+-K+-ATPase caused the loss of Na+ with water and with utake of K+ but the vesicles did not increase in number. Na+-K+ATPase activity was suggested to inhibit vesicle formation by competing for ATP. The loss of water and increase in vesicle number was Ca2+-dependent but did not require Na+. Inhibition of the volume control system by iodoacetamide, Ca2+-free solution and other procedures resulted in swelling of membrane vesicles. The membrane vesicles were suggested to be sites of a mechanochemical system of volume control and the mechanochemical step was suggested to involve discharge of membrane vesicles."} {"id": "PMID:157387", "title": "Crural hypertrophy associated with centronuclear myopathy.", "content": "A case of centronuclear myopathy of adult onset with striking hypertrophy of lower limb muscles in a black South African man is described with details of the light microscopic, histochemical, and ultrastructural features. The association of hypertrophied muscles with centronuclear myopathy has not to our knowledge been reported previously and it is felt that this may be a variant of the condition.", "contents": "Crural hypertrophy associated with centronuclear myopathy. A case of centronuclear myopathy of adult onset with striking hypertrophy of lower limb muscles in a black South African man is described with details of the light microscopic, histochemical, and ultrastructural features. The association of hypertrophied muscles with centronuclear myopathy has not to our knowledge been reported previously and it is felt that this may be a variant of the condition."} {"id": "PMID:157389", "title": "Potassium permanganate induced calcergy: a model to study the effects of drugs on hydroxyapatite crystal deposition.", "content": "Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis.", "contents": "Potassium permanganate induced calcergy: a model to study the effects of drugs on hydroxyapatite crystal deposition. Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis."} {"id": "PMID:157390", "title": "Evaluation of the feto-placental function by means of intraamniotic administration of dehydroepiandrosterone-sulphate.", "content": "It is well known that in pregnancy dehydroepiandrosterone-sulphate (DHEAS) (90% synthetized by the fetal adrenals, 10% by the maternal ones) is converted into estrogens mainly in the placenta. In order to evaluate the steroid metabolizing capacity of the placental enzymatic complex under load conditions, a test was devised based upon a rapid introduction of 200 mg of DHEAS into the amniotic compartment during the third trimester of gestation. The purpose of the present investigation was to establish the clinical utility of such a test in comparison with the simple urinary estrogen determination test.", "contents": "Evaluation of the feto-placental function by means of intraamniotic administration of dehydroepiandrosterone-sulphate. It is well known that in pregnancy dehydroepiandrosterone-sulphate (DHEAS) (90% synthetized by the fetal adrenals, 10% by the maternal ones) is converted into estrogens mainly in the placenta. In order to evaluate the steroid metabolizing capacity of the placental enzymatic complex under load conditions, a test was devised based upon a rapid introduction of 200 mg of DHEAS into the amniotic compartment during the third trimester of gestation. The purpose of the present investigation was to establish the clinical utility of such a test in comparison with the simple urinary estrogen determination test."} {"id": "PMID:157391", "title": "Harm-doing and victim's racial or orthopedic stigma as determinants of helping behavior.", "content": "Three experiments tested a prediction derived from an ambivalence theory of behavior toward the stigmatized. The prediction was that unintentional harm-doers would be more likely to make restitution by doing a favor for a stigmatized victim than for a nonstigmatized one. In Experiment 1 it was upheld for black versus white victims. In Experiment 2, where the victim of harm-doing was either physically handicapped or normal, the prediction was upheld only among older subjects, following the post hoc introduction of an age variable. Experiment 3 also used a physical disability variable. The data were consistent with the prediction, although the adequacy of the harm-doing manipulation was not checked empirically. On the whole, these results are seen as complementing previous findings of amplified post-harm-doing denigration of black and disabled victims. An assumption that the relationship between harm-doing and altruism was mediated by guilt arousal received only fragmentary support. That is, self-reports of guilt were highest in the harm-doing black confederate condition in Experiment 1, and self-reports of negative affect were highest in the harm-doing/wheelchair confederate condition in Experiment 3, but there were no significant relationships between individual differences in guilt or negative affect on the one hand, and amount of helping, on the other.", "contents": "Harm-doing and victim's racial or orthopedic stigma as determinants of helping behavior. Three experiments tested a prediction derived from an ambivalence theory of behavior toward the stigmatized. The prediction was that unintentional harm-doers would be more likely to make restitution by doing a favor for a stigmatized victim than for a nonstigmatized one. In Experiment 1 it was upheld for black versus white victims. In Experiment 2, where the victim of harm-doing was either physically handicapped or normal, the prediction was upheld only among older subjects, following the post hoc introduction of an age variable. Experiment 3 also used a physical disability variable. The data were consistent with the prediction, although the adequacy of the harm-doing manipulation was not checked empirically. On the whole, these results are seen as complementing previous findings of amplified post-harm-doing denigration of black and disabled victims. An assumption that the relationship between harm-doing and altruism was mediated by guilt arousal received only fragmentary support. That is, self-reports of guilt were highest in the harm-doing black confederate condition in Experiment 1, and self-reports of negative affect were highest in the harm-doing/wheelchair confederate condition in Experiment 3, but there were no significant relationships between individual differences in guilt or negative affect on the one hand, and amount of helping, on the other."} {"id": "PMID:157392", "title": "The relationship between two personality questionnaires: the Mini-Mult and the 16PF-E.", "content": "The Mini-Mult and 16PF-E were administered to a heterogeneous sample of 216 clients. Several multivariate analyses were conducted to specify the common and unique information that these two brief instruments generate. While the 16PF-E provides a global estimate of the client's overall level of emotional adjustment, as well as information regarding a wide range of non-pathological traits, the Mini-Mult focuses on subtle aspects of maladjustment corresponding to traditional psychiatric syndromes. For preliminary screening purposes the 16PF-E results in a broader assessment of personality functioning.", "contents": "The relationship between two personality questionnaires: the Mini-Mult and the 16PF-E. The Mini-Mult and 16PF-E were administered to a heterogeneous sample of 216 clients. Several multivariate analyses were conducted to specify the common and unique information that these two brief instruments generate. While the 16PF-E provides a global estimate of the client's overall level of emotional adjustment, as well as information regarding a wide range of non-pathological traits, the Mini-Mult focuses on subtle aspects of maladjustment corresponding to traditional psychiatric syndromes. For preliminary screening purposes the 16PF-E results in a broader assessment of personality functioning."} {"id": "PMID:157394", "title": "Abnormal children of a 47,XYY father.", "content": "Abnormal children of two 47,XYY men were studied. One of these men had 2 normal daughters and a child, 45,X/46,XY, with gonadal dysgenesis. The other man had 2 normal sons and a child with Down's syndrome. The extra chromosome 21 of this child came from the mother. Another 47,XYY man had 4 normal children.", "contents": "Abnormal children of a 47,XYY father. Abnormal children of two 47,XYY men were studied. One of these men had 2 normal daughters and a child, 45,X/46,XY, with gonadal dysgenesis. The other man had 2 normal sons and a child with Down's syndrome. The extra chromosome 21 of this child came from the mother. Another 47,XYY man had 4 normal children."} {"id": "PMID:157395", "title": "Two balanced translocations in three generations of a pedigree: t(7;10) (q11;q22) and t(14;21) (14qter to cen to 21qter)1.", "content": "A reciprocal chromosome translocation between 7q and 10q and an unrelated Robertsonian translocation involving 14q and 21q were found in a healthy 44-year-old man, in his normal 18-year-old son, and in his mother. They were ascertained through the man's brother, whose grandson has Down's syndrome as a result of an inherited 14q21q translocation. To our knowledge, this is the second report of a karyotype with both reciprocal and Robertsonian translocations in a single subject, and only the fourth report of independently segregating double translocations occurring in more than one generation.", "contents": "Two balanced translocations in three generations of a pedigree: t(7;10) (q11;q22) and t(14;21) (14qter to cen to 21qter)1. A reciprocal chromosome translocation between 7q and 10q and an unrelated Robertsonian translocation involving 14q and 21q were found in a healthy 44-year-old man, in his normal 18-year-old son, and in his mother. They were ascertained through the man's brother, whose grandson has Down's syndrome as a result of an inherited 14q21q translocation. To our knowledge, this is the second report of a karyotype with both reciprocal and Robertsonian translocations in a single subject, and only the fourth report of independently segregating double translocations occurring in more than one generation."} {"id": "PMID:157396", "title": "Normal phenotype and partial trisomy for the G positive region of chromosome 21.", "content": "A prenatally diagnosed male fetus and his mother, who was referred because of her advanced age, both carried an abnormal bisatellited chromosome 21 as an extra chromosome. The abnormal 21 was monocentric and the G negative band q22 and part of q21 had been deleted during formation. The phenotype of both the mother and child (at birth) was normal.", "contents": "Normal phenotype and partial trisomy for the G positive region of chromosome 21. A prenatally diagnosed male fetus and his mother, who was referred because of her advanced age, both carried an abnormal bisatellited chromosome 21 as an extra chromosome. The abnormal 21 was monocentric and the G negative band q22 and part of q21 had been deleted during formation. The phenotype of both the mother and child (at birth) was normal."} {"id": "PMID:157397", "title": "New treatment for seborrheic alopecia: the ligature of the arteries of the scalp.", "content": "Bilateral ligature of the superficial temporal arteries and of the posterior auricular arteries is proposed as a treatment for seborrheic alopecia. The arterial circulatory dynamics are, thus, replaced by capillary circulatory dynamics. Hypoxia is produced which inhibits enzymatic systems and lessens nocuous action of androgen and lipid factors on the pilosebaceous effectors. The histologic study shows that the production of sebum is greatly reduced and the condition of the hair follicle is strikingly improved.", "contents": "New treatment for seborrheic alopecia: the ligature of the arteries of the scalp. Bilateral ligature of the superficial temporal arteries and of the posterior auricular arteries is proposed as a treatment for seborrheic alopecia. The arterial circulatory dynamics are, thus, replaced by capillary circulatory dynamics. Hypoxia is produced which inhibits enzymatic systems and lessens nocuous action of androgen and lipid factors on the pilosebaceous effectors. The histologic study shows that the production of sebum is greatly reduced and the condition of the hair follicle is strikingly improved."} {"id": "PMID:157398", "title": "Membrane fluidity and fatty acid composition of phospholipids in erythrocyte membranes of patients with Huntington disease.", "content": "A study was undertaken to determine whether alterations in the configuration of erythrocyte membranes of patients with Huntington disease, reported by other investigators, could be reflected in membrane fluidity-viscosity. Since membrane fluidity appears to be related to the fatty acid composition of membrane phospholipids, these were also examined. Membrane fluidity, which was determined by measuring the intrinsic fluorescence of membranous tryptophan, was found to be normal. Although the range of fatty acid distribution within the various phospholipids tended to vary somewhat, the pattern was not significantly different from that of the controls.", "contents": "Membrane fluidity and fatty acid composition of phospholipids in erythrocyte membranes of patients with Huntington disease. A study was undertaken to determine whether alterations in the configuration of erythrocyte membranes of patients with Huntington disease, reported by other investigators, could be reflected in membrane fluidity-viscosity. Since membrane fluidity appears to be related to the fatty acid composition of membrane phospholipids, these were also examined. Membrane fluidity, which was determined by measuring the intrinsic fluorescence of membranous tryptophan, was found to be normal. Although the range of fatty acid distribution within the various phospholipids tended to vary somewhat, the pattern was not significantly different from that of the controls."} {"id": "PMID:157399", "title": "Effects of 2-nicotinamidoethyl nitrate (SG-75) on dog coronary artery and cat papillary muscle.", "content": "Effects of 2-nicotinamidoethyl nitrate (SG-75) on isolated dog coronary artery and cat papillary muscle were investigated. SG-75 dose-dependently relaxed the isolated coronary arterial strips contracted with potassium. Large doses of SG-75 depressed contraction of papillary muscle driven with electrical stimulation and inhibited enhancement of contraction of papillary muscle induced by calcium and isoproterenol. From these results it is suggested that SG-75 may have a weak Ca++-antagonistic action.", "contents": "Effects of 2-nicotinamidoethyl nitrate (SG-75) on dog coronary artery and cat papillary muscle. Effects of 2-nicotinamidoethyl nitrate (SG-75) on isolated dog coronary artery and cat papillary muscle were investigated. SG-75 dose-dependently relaxed the isolated coronary arterial strips contracted with potassium. Large doses of SG-75 depressed contraction of papillary muscle driven with electrical stimulation and inhibited enhancement of contraction of papillary muscle induced by calcium and isoproterenol. From these results it is suggested that SG-75 may have a weak Ca++-antagonistic action."} {"id": "PMID:157405", "title": "[Hypertrophic cardiomyopathy in children (clinico-echocardiographic study)].", "content": "On the grounds of clinical, electro- and echo-cardiographic examination of 39 patients with hypertrophic cardiomyopathy from 3 to 15 years of age three types of this pathological condition are distinguished: asymmetrical septal hypertrophy, idiopathic hypertrophic subaortic stenosis and symmetrical hypertrophic cardiomyopathy. The value of signs of hypertrophic myopathy obtained on clinical and instrumental examination is discussed. The high diagnostic value of echocardiography in the examination of patients is emphasized.", "contents": "[Hypertrophic cardiomyopathy in children (clinico-echocardiographic study)]. On the grounds of clinical, electro- and echo-cardiographic examination of 39 patients with hypertrophic cardiomyopathy from 3 to 15 years of age three types of this pathological condition are distinguished: asymmetrical septal hypertrophy, idiopathic hypertrophic subaortic stenosis and symmetrical hypertrophic cardiomyopathy. The value of signs of hypertrophic myopathy obtained on clinical and instrumental examination is discussed. The high diagnostic value of echocardiography in the examination of patients is emphasized."} {"id": "PMID:157406", "title": "The structure, function, and turnover of cardiac myosin in normal and myopathic Syrian hamsters.", "content": "Cardiac myosin was examined during the four pathologic stages of cardiomyopathy in strain BIO 14.6 of Syrian hamsters. It was determined that the Ca2+- and K+-ethylenediaminetetraacetic acid (EDTA)-activated ATPase activities of ventricular myosin were significantly reduced during the final stage of the inherited disease. One- and 2-dimensional gel electrophoresis of myosin samples at all stages failed to yield any evidence for a change in the subunit structure of myosin based on light chain number, molecular weight, and per cent composition. The final stage of the disease was characterized by altered protein metabolism. The rates of synthesis and degradation were both altered in the diseased tissue, and a net loss of myosin resulting from a substantial increase in the rate of degradation.", "contents": "The structure, function, and turnover of cardiac myosin in normal and myopathic Syrian hamsters. Cardiac myosin was examined during the four pathologic stages of cardiomyopathy in strain BIO 14.6 of Syrian hamsters. It was determined that the Ca2+- and K+-ethylenediaminetetraacetic acid (EDTA)-activated ATPase activities of ventricular myosin were significantly reduced during the final stage of the inherited disease. One- and 2-dimensional gel electrophoresis of myosin samples at all stages failed to yield any evidence for a change in the subunit structure of myosin based on light chain number, molecular weight, and per cent composition. The final stage of the disease was characterized by altered protein metabolism. The rates of synthesis and degradation were both altered in the diseased tissue, and a net loss of myosin resulting from a substantial increase in the rate of degradation."} {"id": "PMID:157417", "title": "[Difficulties of expert testimony in microwave disease].", "content": "Difficulties in certification of microwave diseases are due to the fact that exposure parameters are not well known and the knowledge of all possible clinical pictures of these diseases is incomplete. To give evidence of this conclusion the author presents 3 cases from the certificatory material of Occupational Diseases Ward within the Clinic of the Institute of Occupational Medicine in L\u00f3d\u017a.", "contents": "[Difficulties of expert testimony in microwave disease]. Difficulties in certification of microwave diseases are due to the fact that exposure parameters are not well known and the knowledge of all possible clinical pictures of these diseases is incomplete. To give evidence of this conclusion the author presents 3 cases from the certificatory material of Occupational Diseases Ward within the Clinic of the Institute of Occupational Medicine in L\u00f3d\u017a."} {"id": "PMID:157418", "title": "Role of purine base excretion in regulation of purine pools.", "content": "Wild type and mutant strains of Neurospora crassa excrete hypoxanthine, xanthine, and uric acid, but not adenine or inosine, when exogenous adenine is added to growing cultures. No detectable excretion occurs in the absence of adenine. The de novo pathway of purine biosynthesis was found to influence the excretion, in that a metabolic block immediately prior to IMP significantly decreased the excretion, while a metabolic block immediately after IMP significantly increased the excretion over that of wild type. The purine catabolic pathway, which is sensitive to ammonia regulation, was found to be a key determinant in the amount and type of excretion. Recently, it was suggested that hypoxanthine accumulation is the result of a mechanism to regulate the adenylate pool size (Leung and Schramm, 1978). In this report, the possibility that hypoxanthine excretion controls adenylate and guanylate pool sizes is discussed and the role of the purine nucleotide cycle in hypoxanthine excretion is examined.", "contents": "Role of purine base excretion in regulation of purine pools. Wild type and mutant strains of Neurospora crassa excrete hypoxanthine, xanthine, and uric acid, but not adenine or inosine, when exogenous adenine is added to growing cultures. No detectable excretion occurs in the absence of adenine. The de novo pathway of purine biosynthesis was found to influence the excretion, in that a metabolic block immediately prior to IMP significantly decreased the excretion, while a metabolic block immediately after IMP significantly increased the excretion over that of wild type. The purine catabolic pathway, which is sensitive to ammonia regulation, was found to be a key determinant in the amount and type of excretion. Recently, it was suggested that hypoxanthine accumulation is the result of a mechanism to regulate the adenylate pool size (Leung and Schramm, 1978). In this report, the possibility that hypoxanthine excretion controls adenylate and guanylate pool sizes is discussed and the role of the purine nucleotide cycle in hypoxanthine excretion is examined."} {"id": "PMID:157420", "title": "Female sterilization using an elasticated silicone ring.", "content": "This paper presents the experience, in a District General Hospital, of using an elasticated silicone ring applied to the Fallopian tubes by the laparoscope. It is concluded that this is a safe and effective method of female sterilization, with good patient acceptance.", "contents": "Female sterilization using an elasticated silicone ring. This paper presents the experience, in a District General Hospital, of using an elasticated silicone ring applied to the Fallopian tubes by the laparoscope. It is concluded that this is a safe and effective method of female sterilization, with good patient acceptance."} {"id": "PMID:157421", "title": "Genetic screening in Western Australia.", "content": "The wider application of genetic screening is described in four Western Australian populations. Counselling with prenatal diagnosis of Down's syndrome was offered to 57 women over the age of 35 years and less than 16 weeks' gestation who attended an antenatal outpatients department. Forty-four women consented to amniocentesis and two affected fetuses were found. Both public and private patients can be screened to detect fetuses with Down's syndrome. In a population of 200 pregnant girls whose infants were intended for adoption, a specially designed family history form aided identification of genetic disorders in 32 families. Counselling was offered to the biological parents, to the adoptive parents, and, prospectively, to the child in later years. The effectiveness of the family history as a screening device is illustrated in this adoption sample. Counselling of parents of 20 decreased malformed infants initiated the genetic counselling clinic in Western Australia and led to subsequent referral of 92 similar cases by the family doctors. It was found that parents who gave birth to malformed infants welcome information and risk figures. Diagnostic screening in a population of 6000 intellectually handicapped individuals yielded 1372 cases (23%) with Mendelian, multifactorial, or chromosomal modes of inheritance. This screening enabled patients with inherited causes for their intellectual handicap to be identified and placed on a register for health planning.", "contents": "Genetic screening in Western Australia. The wider application of genetic screening is described in four Western Australian populations. Counselling with prenatal diagnosis of Down's syndrome was offered to 57 women over the age of 35 years and less than 16 weeks' gestation who attended an antenatal outpatients department. Forty-four women consented to amniocentesis and two affected fetuses were found. Both public and private patients can be screened to detect fetuses with Down's syndrome. In a population of 200 pregnant girls whose infants were intended for adoption, a specially designed family history form aided identification of genetic disorders in 32 families. Counselling was offered to the biological parents, to the adoptive parents, and, prospectively, to the child in later years. The effectiveness of the family history as a screening device is illustrated in this adoption sample. Counselling of parents of 20 decreased malformed infants initiated the genetic counselling clinic in Western Australia and led to subsequent referral of 92 similar cases by the family doctors. It was found that parents who gave birth to malformed infants welcome information and risk figures. Diagnostic screening in a population of 6000 intellectually handicapped individuals yielded 1372 cases (23%) with Mendelian, multifactorial, or chromosomal modes of inheritance. This screening enabled patients with inherited causes for their intellectual handicap to be identified and placed on a register for health planning."} {"id": "PMID:157427", "title": "[Composite materials in pedodontics].", "content": "A brief account is given of the features of 1st and 2nd generation compounds and their clinical applications. Reference is made to many years of personal experience in an assessment of their long-term results.", "contents": "[Composite materials in pedodontics]. A brief account is given of the features of 1st and 2nd generation compounds and their clinical applications. Reference is made to many years of personal experience in an assessment of their long-term results."} {"id": "PMID:157432", "title": "Relationships between satellite association and the occurrence of non-disjunction in man.", "content": "It has been reported that there is an increased incidence of Down's syndrome among the children of parents who have been exposed to ionizing radiations for radiodiagnostic or radiotherapeutic reasons. Work with Drosophila, mice and human lymphocytes has shown that irradiation with X- or gamma-rays induces aneuploidy, presumably by non-disjunction. It has been suggested that in man the frequency of satellite association (s.a.) of acrocentric chromosomes may be involved in the causation of chromosomal non-disjunction. In the present work the effects of radiation on s.a. have, therefore, been investigated. The frequency of s.a. between acrocentric chromosomes was determined after the exposure of human blood from normal and chromosomally abnormal individuals to various small doses of Co-60 gamma-rays. The criteria of Zang and Back were used for the evaluation of s.a. complexes. No effects of radiation on the frequency of s.a. were apparent within the dose range investigated. The same result was obtained when s.a. was evaluated using the silver-staining technique in which physical connections between the associating satellites may be observed and the association complexes evaluated directly. The effects of other radiation sources have also been investigated.", "contents": "Relationships between satellite association and the occurrence of non-disjunction in man. It has been reported that there is an increased incidence of Down's syndrome among the children of parents who have been exposed to ionizing radiations for radiodiagnostic or radiotherapeutic reasons. Work with Drosophila, mice and human lymphocytes has shown that irradiation with X- or gamma-rays induces aneuploidy, presumably by non-disjunction. It has been suggested that in man the frequency of satellite association (s.a.) of acrocentric chromosomes may be involved in the causation of chromosomal non-disjunction. In the present work the effects of radiation on s.a. have, therefore, been investigated. The frequency of s.a. between acrocentric chromosomes was determined after the exposure of human blood from normal and chromosomally abnormal individuals to various small doses of Co-60 gamma-rays. The criteria of Zang and Back were used for the evaluation of s.a. complexes. No effects of radiation on the frequency of s.a. were apparent within the dose range investigated. The same result was obtained when s.a. was evaluated using the silver-staining technique in which physical connections between the associating satellites may be observed and the association complexes evaluated directly. The effects of other radiation sources have also been investigated."} {"id": "PMID:157433", "title": "Fatal lymphoma after transplantation of cultured thymus in children with combined immunodeficiency disease.", "content": "A fatal, widespread, polyclonal, B-cell immunoblastic lymphoproliferative disorder developed in three children with combined immunodeficiency shortly after intra-abdominal transplantation of cultured thymus epithelium for immunoreconstitution. All three had surface immunoglobulin-bearing cells (15 to 20 per cent) in the peripheral blood before transplantation and polyclonally elevated immunoglobulins afterward. Abnormal immunoregulation was demonstrated by a lack of concanavalin A-induced suppressor-cell activity in mixed leukocyte culture in all three patients before transplantation and in two afterward. We suggest that the transplant acted as a promoter through immunostimulation or production of promoter factors, and that excessive polyclonal B-cell proliferation resulted because of inadequate immunoregulatory mechanisms. Although this complication occurred in only three of 30 patients with various forms of immunodeficiency treated with cultured thymus, these cases illustrate a potential problem in immunoreconstitution of combined immunodeficiency disorders.", "contents": "Fatal lymphoma after transplantation of cultured thymus in children with combined immunodeficiency disease. A fatal, widespread, polyclonal, B-cell immunoblastic lymphoproliferative disorder developed in three children with combined immunodeficiency shortly after intra-abdominal transplantation of cultured thymus epithelium for immunoreconstitution. All three had surface immunoglobulin-bearing cells (15 to 20 per cent) in the peripheral blood before transplantation and polyclonally elevated immunoglobulins afterward. Abnormal immunoregulation was demonstrated by a lack of concanavalin A-induced suppressor-cell activity in mixed leukocyte culture in all three patients before transplantation and in two afterward. We suggest that the transplant acted as a promoter through immunostimulation or production of promoter factors, and that excessive polyclonal B-cell proliferation resulted because of inadequate immunoregulatory mechanisms. Although this complication occurred in only three of 30 patients with various forms of immunodeficiency treated with cultured thymus, these cases illustrate a potential problem in immunoreconstitution of combined immunodeficiency disorders."} {"id": "PMID:157441", "title": "Anatomo-radiological considerations about lumbar discography. An experimental study.", "content": "An experimental study was undertaken to determine the origin of lumbar pain associated with degeneration of lumbar intervertebral disc by examining their innervation, vascularization, and stages of evolution. The study included the comparison of discography on patients with an experimental reproduction of this examination on cadavers.", "contents": "Anatomo-radiological considerations about lumbar discography. An experimental study. An experimental study was undertaken to determine the origin of lumbar pain associated with degeneration of lumbar intervertebral disc by examining their innervation, vascularization, and stages of evolution. The study included the comparison of discography on patients with an experimental reproduction of this examination on cadavers."} {"id": "PMID:157442", "title": "Erythrocyte ATP in Duchenne dystrophy: effects of ouabain and propranolol.", "content": "The ATP and lactate contents of erythrocytes from patients with Duchenne muscular dystrophy (DMD) were measured before and after incubation with or without glucose plus either ouabain or propranolol. Samples from patients and controls were obtained at almost the same time on the same day and processed simultaneously. The erythrocyte ATP content differed in adults and children, but there was no difference between DMD patients and age-matched controls. Ouabain suppressed, and propranolol enhanced, the changes of ATP and lactate, to the same extent in patients and in controls. We found no gross abnormalities in generation and utilization of ATP in erythrocytes in DMD, and the response to ouabain or propranolol appeared normal.", "contents": "Erythrocyte ATP in Duchenne dystrophy: effects of ouabain and propranolol. The ATP and lactate contents of erythrocytes from patients with Duchenne muscular dystrophy (DMD) were measured before and after incubation with or without glucose plus either ouabain or propranolol. Samples from patients and controls were obtained at almost the same time on the same day and processed simultaneously. The erythrocyte ATP content differed in adults and children, but there was no difference between DMD patients and age-matched controls. Ouabain suppressed, and propranolol enhanced, the changes of ATP and lactate, to the same extent in patients and in controls. We found no gross abnormalities in generation and utilization of ATP in erythrocytes in DMD, and the response to ouabain or propranolol appeared normal."} {"id": "PMID:157443", "title": "Disability benefits as disincentives to rehabilitation.", "content": "The relations among physical disability, governmental and voluntary benefit programs, and rehabilitation outcome are more complex than has generally been assumed. Factors of motivation and functional capacity are not adequately accommodated by current methods and level of benefit provision. Preliminary investigation shows that programs may, in fact, deter some of the disabled from return to work. Proposed congressional legislation does not appear to likely to resolve conflicting goals and expectations of the labor market, the disabled, and the taxpayer.", "contents": "Disability benefits as disincentives to rehabilitation. The relations among physical disability, governmental and voluntary benefit programs, and rehabilitation outcome are more complex than has generally been assumed. Factors of motivation and functional capacity are not adequately accommodated by current methods and level of benefit provision. Preliminary investigation shows that programs may, in fact, deter some of the disabled from return to work. Proposed congressional legislation does not appear to likely to resolve conflicting goals and expectations of the labor market, the disabled, and the taxpayer."} {"id": "PMID:157448", "title": "Neurological complications, following lumbar radiculography with Dimer X.", "content": "Three cases developing increasing neurological deficit within 24 hours of lumbar radiculography with Dimer X are reported. All three developed severe low back and sciatic pain, and myoclonic spasms within one hour of the examination. In each a large intervertebral disc prolapse was outlined. Two cases developed near complete paraplegia before surgical decompression. Following surgery, two patients made a complete rapid recovery, and the other has recovered partially.", "contents": "Neurological complications, following lumbar radiculography with Dimer X. Three cases developing increasing neurological deficit within 24 hours of lumbar radiculography with Dimer X are reported. All three developed severe low back and sciatic pain, and myoclonic spasms within one hour of the examination. In each a large intervertebral disc prolapse was outlined. Two cases developed near complete paraplegia before surgical decompression. Following surgery, two patients made a complete rapid recovery, and the other has recovered partially."} {"id": "PMID:157453", "title": "In vivo and in vitro assays of immunocompetence in bronchogenic carcinoma.", "content": "To determine the degree of correlation among the various in vivo and in vitro assays that could be used to assess immunocompetence in bronchogenic carcinoma, the response to common recall skin antigens, primary sensitization to DNCB and lymphocyte function tests based on blastogenic response to mitogens and in mixed lymphocyte culture (MLC) were tested in 48 patients with bronchogenic carcinoma. The values were compared to responses in 94 age-matched healthy control subjects. There were impaired skin tests reactions among squamous cell carcinoma patients, with little impairment of their lymphocyte blastogenesis reactions. Anaplastic carcinoma patients had notable defects in lymphocyte function tests but less impairment of the skin test reactions. These data suggest that the mitogen concanavalin A, phytohemagglutinin, and the MLC are more useful screening assays of in vitro immunocompetence than are the other commonly used mitogens.", "contents": "In vivo and in vitro assays of immunocompetence in bronchogenic carcinoma. To determine the degree of correlation among the various in vivo and in vitro assays that could be used to assess immunocompetence in bronchogenic carcinoma, the response to common recall skin antigens, primary sensitization to DNCB and lymphocyte function tests based on blastogenic response to mitogens and in mixed lymphocyte culture (MLC) were tested in 48 patients with bronchogenic carcinoma. The values were compared to responses in 94 age-matched healthy control subjects. There were impaired skin tests reactions among squamous cell carcinoma patients, with little impairment of their lymphocyte blastogenesis reactions. Anaplastic carcinoma patients had notable defects in lymphocyte function tests but less impairment of the skin test reactions. These data suggest that the mitogen concanavalin A, phytohemagglutinin, and the MLC are more useful screening assays of in vitro immunocompetence than are the other commonly used mitogens."} {"id": "PMID:157454", "title": "The absence of proprioceptive nerve endings in the human periodontal ligament: the role of periodontal mechanoreceptors in the reflex control of mastication.", "content": "A review of the literature was conducted to determine the presence or absence of proprioceptive nerve endings in the human periodontal ligament. A histologic review of the periodontal ligament innervation concluded that nerve endings found were those mediating pain, pressure, or touch and that there is no histologic evidence of any \"classic\" proprioceptive nerve ending in the periodontal ligament. A summary is given concerning the precise role of nerve endings in the periodontal membrane, their afferent pathways, and the role of masticatory muscle proprioception, jaw reflexes, and the temporomandibular joint in the coordinated control of mastication and mandibular proprioception.", "contents": "The absence of proprioceptive nerve endings in the human periodontal ligament: the role of periodontal mechanoreceptors in the reflex control of mastication. A review of the literature was conducted to determine the presence or absence of proprioceptive nerve endings in the human periodontal ligament. A histologic review of the periodontal ligament innervation concluded that nerve endings found were those mediating pain, pressure, or touch and that there is no histologic evidence of any \"classic\" proprioceptive nerve ending in the periodontal ligament. A summary is given concerning the precise role of nerve endings in the periodontal membrane, their afferent pathways, and the role of masticatory muscle proprioception, jaw reflexes, and the temporomandibular joint in the coordinated control of mastication and mandibular proprioception."} {"id": "PMID:157455", "title": "Antibody formation to dog pulp tissue altered by AH-26 sealer via the root canal.", "content": "Pulp tissue from three experimental dogs was tested for its antigenicity before and after incubation with AH-26 sealer. identical to Reactions to Arthus skin tests showed an increased response to pulp that had been incubated in AH-26, washed, and then injected, as compared with the material alone. Hemagglutinating antibody titers (1/500 to 1/800) were obtained from pulp tissue altered by AH-26. Inhibition tests showed the apecificity of the antibody to be at a dilution titer of 1:400. Therefore, a mixture of AH-26 sealer altered dog pulp tissue and rendered it antigenically active, and a specific humoral response was produced.", "contents": "Antibody formation to dog pulp tissue altered by AH-26 sealer via the root canal. Pulp tissue from three experimental dogs was tested for its antigenicity before and after incubation with AH-26 sealer. identical to Reactions to Arthus skin tests showed an increased response to pulp that had been incubated in AH-26, washed, and then injected, as compared with the material alone. Hemagglutinating antibody titers (1/500 to 1/800) were obtained from pulp tissue altered by AH-26. Inhibition tests showed the apecificity of the antibody to be at a dilution titer of 1:400. Therefore, a mixture of AH-26 sealer altered dog pulp tissue and rendered it antigenically active, and a specific humoral response was produced."} {"id": "PMID:157461", "title": "[The left ventricle at different stages of a two steps mechanical overloading. Electron microscopic study in the rat (author's transl)].", "content": "The left ventricle myocardium of rats subjected to a two steps mechanical overloading (abdominal aorta constriction + aortic insufficiency) was examined in the light and electron microscopes at several stages of the load, and particularly after 3 to 6 months when the animals exhibited congestive heart failure. In these conditions, the heart weight exceeded the control by more than 100 %. In the later stages, the absence of parallelism between heart weight and cell diameter was compatible with a process of hyperplasia. Cellular lesions looking like recent were found more and more frequently with time. Within apparently normal cells proliferation of small mitochondria, nucleoli and Golgi apparatus are compatible with some deficit in energy balance, which is usually encountered only in early stages of the load.", "contents": "[The left ventricle at different stages of a two steps mechanical overloading. Electron microscopic study in the rat (author's transl)]. The left ventricle myocardium of rats subjected to a two steps mechanical overloading (abdominal aorta constriction + aortic insufficiency) was examined in the light and electron microscopes at several stages of the load, and particularly after 3 to 6 months when the animals exhibited congestive heart failure. In these conditions, the heart weight exceeded the control by more than 100 %. In the later stages, the absence of parallelism between heart weight and cell diameter was compatible with a process of hyperplasia. Cellular lesions looking like recent were found more and more frequently with time. Within apparently normal cells proliferation of small mitochondria, nucleoli and Golgi apparatus are compatible with some deficit in energy balance, which is usually encountered only in early stages of the load."} {"id": "PMID:157462", "title": "The relationship of adrenal androgens to the secretory patterns for cortisol, prolactin, and growth hormone during early puberty.", "content": "Serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHA-sulfate), cortisol, prolactin, and growth hormone were measured at half-hour intervals for 24 hr in five healthy children aged 8--13 yr. Their adolescent development was assessed by clinical staging, plus determinations of serum FSH, LH, testosterone and estradiol during both wakefulness and sleep. Correlative analysis indicates that there was synchronous secretion of DHA and cortisol, implying regulation of both by ACTH. With advancing age and sexual maturation, there was a progressive rise in mean serum DHA and DHA-sulfate levels, but no similar change in serum cortisol concentrations. There was evidence for enhanced secretion of both growth hormone and prolactin during sleep in all subjects (including one who was hyperprolactinemic), but there was no obvious relationship between levels of these pituitary hormones and the early pubertal rise in adrenal androgens.", "contents": "The relationship of adrenal androgens to the secretory patterns for cortisol, prolactin, and growth hormone during early puberty. Serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHA-sulfate), cortisol, prolactin, and growth hormone were measured at half-hour intervals for 24 hr in five healthy children aged 8--13 yr. Their adolescent development was assessed by clinical staging, plus determinations of serum FSH, LH, testosterone and estradiol during both wakefulness and sleep. Correlative analysis indicates that there was synchronous secretion of DHA and cortisol, implying regulation of both by ACTH. With advancing age and sexual maturation, there was a progressive rise in mean serum DHA and DHA-sulfate levels, but no similar change in serum cortisol concentrations. There was evidence for enhanced secretion of both growth hormone and prolactin during sleep in all subjects (including one who was hyperprolactinemic), but there was no obvious relationship between levels of these pituitary hormones and the early pubertal rise in adrenal androgens."} {"id": "PMID:157480", "title": "Colorectal carcinoma: overview of management techniques.", "content": "The fact that the national death rate from carcinoma of the colon and rectum has remained static over the past two decades is strong incentive for future investigation of measures to allow detection in its early and more favorable stage. Although no significant improvements in surgical techniques have afforded improvement in longevity, certain technical factors are known to inhibit tumor implantation during surgery. Data suggest that the extent of en bloc resection is the most crucial factor in avoiding recurrence. Extensive use of radiotherapy as the sole method of treatment or as preoperative or postoperative adjunctive therapy remains investigational, but it seems likely that this form of treatment will play an increasing role in the future. Preoperative radiotherapy seems to be useful in reducing the stage of the neoplasm and the incidence of extraserosal involvement; postoperative radiotherapy is beneficial for palliation. Chemotherapy, particularly with the fluorinated pyrimidines (5-FU and 5-FUDR), is being evaluated for its usefulness in lengthening survival time; response to 5-FU is occasionally dramatic. It remains for major investigational centers to clarify the role of combination chemotherapy in metastatic disease. Immunotherapy at present must be considered an unproven mode of treatment and of inconclusive benefit in any stage of colorectal carcinoma. Carcinoembryonic antigen assay is a useful prognostic and diagnostic tool in localizing primary tumor and in subsequent evaluation of response to treatment.", "contents": "Colorectal carcinoma: overview of management techniques. The fact that the national death rate from carcinoma of the colon and rectum has remained static over the past two decades is strong incentive for future investigation of measures to allow detection in its early and more favorable stage. Although no significant improvements in surgical techniques have afforded improvement in longevity, certain technical factors are known to inhibit tumor implantation during surgery. Data suggest that the extent of en bloc resection is the most crucial factor in avoiding recurrence. Extensive use of radiotherapy as the sole method of treatment or as preoperative or postoperative adjunctive therapy remains investigational, but it seems likely that this form of treatment will play an increasing role in the future. Preoperative radiotherapy seems to be useful in reducing the stage of the neoplasm and the incidence of extraserosal involvement; postoperative radiotherapy is beneficial for palliation. Chemotherapy, particularly with the fluorinated pyrimidines (5-FU and 5-FUDR), is being evaluated for its usefulness in lengthening survival time; response to 5-FU is occasionally dramatic. It remains for major investigational centers to clarify the role of combination chemotherapy in metastatic disease. Immunotherapy at present must be considered an unproven mode of treatment and of inconclusive benefit in any stage of colorectal carcinoma. Carcinoembryonic antigen assay is a useful prognostic and diagnostic tool in localizing primary tumor and in subsequent evaluation of response to treatment."} {"id": "PMID:157482", "title": "[Population-genetic studies in the microfoci of endemic goiter].", "content": "The material analysed is referred to 5 goiter endemic microfoci of one of the landscape-geographical zone of the Kama region with a relative iodine deficiency in the environment, caused by disbalance between iodine and other trace elements. Diffuse enlargement of the thyroid gland was revealed in 50.5% of males, and in 69.7% of females; goiter disease was diagnosed in 3.3% of males, and in 11.6% of females. The empirical risk of goiter occurrence for members of the family with one patient suffering from this disease is double, and in the families with two or more patients--is four tunes greater than in the rest of the population. There proved to be statistically significant differences in goiter morbidity among persons with different degree of blood relation to the proband. Calculations by the original method presented demonstrated that familial associations of goiter patients corresponded to monomere autosome-dominant inheritance with an incomplete manifestation of the corresponding genotype within the range of P = 0.7--0.8.", "contents": "[Population-genetic studies in the microfoci of endemic goiter]. The material analysed is referred to 5 goiter endemic microfoci of one of the landscape-geographical zone of the Kama region with a relative iodine deficiency in the environment, caused by disbalance between iodine and other trace elements. Diffuse enlargement of the thyroid gland was revealed in 50.5% of males, and in 69.7% of females; goiter disease was diagnosed in 3.3% of males, and in 11.6% of females. The empirical risk of goiter occurrence for members of the family with one patient suffering from this disease is double, and in the families with two or more patients--is four tunes greater than in the rest of the population. There proved to be statistically significant differences in goiter morbidity among persons with different degree of blood relation to the proband. Calculations by the original method presented demonstrated that familial associations of goiter patients corresponded to monomere autosome-dominant inheritance with an incomplete manifestation of the corresponding genotype within the range of P = 0.7--0.8."} {"id": "PMID:157483", "title": "[Excretion of testosterone, epitestosterone, androstenedione and 7-ketodehydroepiandrostenedione in healthy men of different ages].", "content": "Urinary excretion of testosterone, epitestosterone, androstendion, and 7-keto-dehydroepistendion was studied in 34 healthy men, aged from 20 to 72 years. The maximal excretion of these steroids and observed in men, aged between 20 and 30 years; their reduction was noted with the advance of age.", "contents": "[Excretion of testosterone, epitestosterone, androstenedione and 7-ketodehydroepiandrostenedione in healthy men of different ages]. Urinary excretion of testosterone, epitestosterone, androstendion, and 7-keto-dehydroepistendion was studied in 34 healthy men, aged from 20 to 72 years. The maximal excretion of these steroids and observed in men, aged between 20 and 30 years; their reduction was noted with the advance of age."} {"id": "PMID:157488", "title": "Oral urine recycling in diabetes insipidus (DI) rats--the role of the gut in absorption of some urinary components.", "content": "Brattleboro rats with diabetes insipidus (DI) will, if no other fluid is offered, drink their own previous day's urine. Such oral urine-recycling, where normal elimination is effective only in 15%, does not result in clinical or laboratory signs of uraemia even after 20 days. Serum electrolytes and creatinine remained normal, serum osmolarity and urea were slightly raised, but none of the parameters measured could be classified as uraemic. Extrarenal excretion of electrolytes increased. It is suggested that when the excreted load is represented to the organism from the gut lumen (as opposed to re-presentation into the peritoneal cavity or cessation of renal function) the gut wall serves a protective function by not reabsorbing significant portions of both the inorganic and organic loads in the urine. More detailed analysis will be required to establish this suggestion.", "contents": "Oral urine recycling in diabetes insipidus (DI) rats--the role of the gut in absorption of some urinary components. Brattleboro rats with diabetes insipidus (DI) will, if no other fluid is offered, drink their own previous day's urine. Such oral urine-recycling, where normal elimination is effective only in 15%, does not result in clinical or laboratory signs of uraemia even after 20 days. Serum electrolytes and creatinine remained normal, serum osmolarity and urea were slightly raised, but none of the parameters measured could be classified as uraemic. Extrarenal excretion of electrolytes increased. It is suggested that when the excreted load is represented to the organism from the gut lumen (as opposed to re-presentation into the peritoneal cavity or cessation of renal function) the gut wall serves a protective function by not reabsorbing significant portions of both the inorganic and organic loads in the urine. More detailed analysis will be required to establish this suggestion."} {"id": "PMID:157489", "title": "Ion transport in the heart atrial tissue of young and adult guinea-pigs and albino rats.", "content": "Rubidium shifts between the extracellular fluid and cells were studied in the isolated atria of guinea-pig and albino rat hearts. In the young of both species, rubidium transport from the incubation medium to the cells was much slower than in preparations from adult animals. That implies that the efficiency of membrane mechanisms for the transport of Na+ and K+ ions in the atrial tissue increases during postnatal life. This conclusion is further confirmed by the finding that the intracellular potassium concentration in the atrial tissue of the young of both species is lower, and the intracellular sodium concentration higher, than in adult animals. Conversely, the serum potassium concentration in the young is higher, and the serum sodium concentration lower, than in adult individuals.", "contents": "Ion transport in the heart atrial tissue of young and adult guinea-pigs and albino rats. Rubidium shifts between the extracellular fluid and cells were studied in the isolated atria of guinea-pig and albino rat hearts. In the young of both species, rubidium transport from the incubation medium to the cells was much slower than in preparations from adult animals. That implies that the efficiency of membrane mechanisms for the transport of Na+ and K+ ions in the atrial tissue increases during postnatal life. This conclusion is further confirmed by the finding that the intracellular potassium concentration in the atrial tissue of the young of both species is lower, and the intracellular sodium concentration higher, than in adult animals. Conversely, the serum potassium concentration in the young is higher, and the serum sodium concentration lower, than in adult individuals."} {"id": "PMID:157493", "title": "Attitudes of families to some aspects of Huntington's chorea.", "content": "One hundred and fifty-three complete questionnaires received from families with a history of Huntington's chorea were analysed to discover their attitudes towards the disease. Of special interest were: (a) how and when they were first informed about their illness; (b) what effects the knowledge of the hereditary aspects of the disease had on them and on their children; and (c) their reaction to a possible future predictive test.", "contents": "Attitudes of families to some aspects of Huntington's chorea. One hundred and fifty-three complete questionnaires received from families with a history of Huntington's chorea were analysed to discover their attitudes towards the disease. Of special interest were: (a) how and when they were first informed about their illness; (b) what effects the knowledge of the hereditary aspects of the disease had on them and on their children; and (c) their reaction to a possible future predictive test."} {"id": "PMID:157494", "title": "Cerebrospinal fluid acetylcholinesterase in neuropsychiatric disorders.", "content": "Acetylcholinesterase (AChE) was measured in the cerebrospinal fluid (CSF) of patients with a diagnosis of Huntington's disease, depression, schizophrenia, or mania and also in the CSF of normal subjects. No significant differences in CSF AChE were found between any diagnostic group and normal subjects. Furthermore, the administration of choline chloride, physostigmine, or probenecid did not significantly alter CSF AChE. No diurnal variation in CSF AChE activity was apparent. These findings, combined with the unclear relationship of brain AChE to CSF AChE, suggest that this measurement does not reflect the relative cholinergic underactivity presumed to exist in some neuropsychiatric conditions.", "contents": "Cerebrospinal fluid acetylcholinesterase in neuropsychiatric disorders. Acetylcholinesterase (AChE) was measured in the cerebrospinal fluid (CSF) of patients with a diagnosis of Huntington's disease, depression, schizophrenia, or mania and also in the CSF of normal subjects. No significant differences in CSF AChE were found between any diagnostic group and normal subjects. Furthermore, the administration of choline chloride, physostigmine, or probenecid did not significantly alter CSF AChE. No diurnal variation in CSF AChE activity was apparent. These findings, combined with the unclear relationship of brain AChE to CSF AChE, suggest that this measurement does not reflect the relative cholinergic underactivity presumed to exist in some neuropsychiatric conditions."} {"id": "PMID:157499", "title": "Clinical implications of the convex supradiaphragmatic inferior vena cava.", "content": "The configuration of the supradiaphragmatic segment of the inferior vena cava (SIVC) was evaluated on lateral chest radiographs to determine the clinical situations in which a posterior convex contour occurred. Of 34 patients with a convex SIVC, 31 had cardiovascular abnormalities. Left ventricular enlargement was present in 17 of 34 (50%), and right ventricular failure in 13 (38%). Valvular regurgitation, left-to-right shunts, narrow anteroposterior chest diameter, and chronic obstructive lung disease were also present. In 102 consecutive normal patients, the SIVC was visible in 97%; only 1 patient had a convex SIVC (p = 10(-7)). The results show that detection of a convex SIVC suggests associated abnormalities.", "contents": "Clinical implications of the convex supradiaphragmatic inferior vena cava. The configuration of the supradiaphragmatic segment of the inferior vena cava (SIVC) was evaluated on lateral chest radiographs to determine the clinical situations in which a posterior convex contour occurred. Of 34 patients with a convex SIVC, 31 had cardiovascular abnormalities. Left ventricular enlargement was present in 17 of 34 (50%), and right ventricular failure in 13 (38%). Valvular regurgitation, left-to-right shunts, narrow anteroposterior chest diameter, and chronic obstructive lung disease were also present. In 102 consecutive normal patients, the SIVC was visible in 97%; only 1 patient had a convex SIVC (p = 10(-7)). The results show that detection of a convex SIVC suggests associated abnormalities."} {"id": "PMID:157512", "title": "[Comparison of various characters and antigenic structure in S. aureus strains cultivated in hospitalized patients and in healthy carriers].", "content": "A comparison has been done between various characters of 170 non epidemic strains cultivated from hospitalized patients and 29 strains originated from healthy carriers without any hospital contact and antibiotic treatment since 6 months. Following characters have been tested: M.I.C. of 13 antibiotics, heterogenous methicillin resistance, enzymatic antibiotic resistance, macrolide inducible or constitutive type resistance, mercuric chloride susceptibility; phage types; enzymes and toxins production. Antigenic structure has been studied, in particular production of protein A, A beta teichoc acid and type antigens. Significant differences have been observed between hospital and healthy carriers strains; these later strains are antibiotic susceptible, produce few toxins and enzymes, are not frequently phage typable. Their antigenic structure shows also significant differences: A beta-teichoic acid is less frequently detected; type antigens are less frequent and different. Role of these surface antigens in virulence is discussed.", "contents": "[Comparison of various characters and antigenic structure in S. aureus strains cultivated in hospitalized patients and in healthy carriers]. A comparison has been done between various characters of 170 non epidemic strains cultivated from hospitalized patients and 29 strains originated from healthy carriers without any hospital contact and antibiotic treatment since 6 months. Following characters have been tested: M.I.C. of 13 antibiotics, heterogenous methicillin resistance, enzymatic antibiotic resistance, macrolide inducible or constitutive type resistance, mercuric chloride susceptibility; phage types; enzymes and toxins production. Antigenic structure has been studied, in particular production of protein A, A beta teichoc acid and type antigens. Significant differences have been observed between hospital and healthy carriers strains; these later strains are antibiotic susceptible, produce few toxins and enzymes, are not frequently phage typable. Their antigenic structure shows also significant differences: A beta-teichoic acid is less frequently detected; type antigens are less frequent and different. Role of these surface antigens in virulence is discussed."} {"id": "PMID:157515", "title": "Induction of chronic diabetes by streptozotocin in the miniature pig.", "content": "The rapid i.v. injection of 60 mg streptozotocin/kg body weight 8 days after an initial dose of 30 mg/kg was the best method to produce a distinct insulin-deficient diabetes in minipigs. Even in the absence of any therapy the further course of this diabetes remained stable without tending to exhibit ketoacidosis. Besides hyperglycaemia and the loss of insulin response to glucose there was significant increase of triglycerides and a decrease of plasma albumin. In the oldest animals this diabetes has so far been observed for more than 3 years. Because of some special advantages this experimental diabetes could provide a useful model for studying diabetic angiopathies.", "contents": "Induction of chronic diabetes by streptozotocin in the miniature pig. The rapid i.v. injection of 60 mg streptozotocin/kg body weight 8 days after an initial dose of 30 mg/kg was the best method to produce a distinct insulin-deficient diabetes in minipigs. Even in the absence of any therapy the further course of this diabetes remained stable without tending to exhibit ketoacidosis. Besides hyperglycaemia and the loss of insulin response to glucose there was significant increase of triglycerides and a decrease of plasma albumin. In the oldest animals this diabetes has so far been observed for more than 3 years. Because of some special advantages this experimental diabetes could provide a useful model for studying diabetic angiopathies."} {"id": "PMID:157516", "title": "Effects of verapamil and aspirin on experimental chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats.", "content": "Rats made hypoxic by confinement in hypoxic cages for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Treatment with Verapamil or aspirin reduced both chronic hypoxic pulmonary hypertension and the hypertrophy of the right ventricle. The antihypertensive effect of Verapamil is explained by the involvement of the transmembrane calcium flux in pulmonary vascular smooth muscle in the hypoxic vasoconstrictory response. Part of the antihypertensive effect of inhibition of prostaglandin synthesis is attributed to a decrease in packed cell volume produced in hypoxic, aspirin treated rats.", "contents": "Effects of verapamil and aspirin on experimental chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats. Rats made hypoxic by confinement in hypoxic cages for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Treatment with Verapamil or aspirin reduced both chronic hypoxic pulmonary hypertension and the hypertrophy of the right ventricle. The antihypertensive effect of Verapamil is explained by the involvement of the transmembrane calcium flux in pulmonary vascular smooth muscle in the hypoxic vasoconstrictory response. Part of the antihypertensive effect of inhibition of prostaglandin synthesis is attributed to a decrease in packed cell volume produced in hypoxic, aspirin treated rats."} {"id": "PMID:157519", "title": "[First results of a surgical treatment of a persistant low-back pain of dorso-lumbar origin].", "content": "Low-back pain may originate in the thoraco-lumbar joints. Due to motion and stress, the latter constitute a high-risk transitional zone. Pain is transmitted by the posterior branches of the D11, D12 or L1 spinal nerves, which innervate the cutaneous and subcutaneous levels of the low-back and upper buttocks region. It is experienced as a deep-seated pain. Clinical examination makes it possible to determine the level responsible. The lumbar pain disappears with anesthesia of the interapophysary articulation. Appropriate medical treatment most often succeeds. If its fails, surgery can provide a solution. It consists of a capsulectomy on the level responsible, and on the upper and lower adjoining regions. This operation also destroys the posterior branch, which is closely joined to the capsule. Out of the 10 cases operated on, there was 1 failure, 6 very good results and 3 good results after follow-up periods of 20 months to 6 months. Without prejudging the future, it seems that there is hope for the treatment of unexplained back pains or those persisting after operations on lumbar disks that are not relieved by appropriate medical treatment of the thoraco-lumbar joints.", "contents": "[First results of a surgical treatment of a persistant low-back pain of dorso-lumbar origin]. Low-back pain may originate in the thoraco-lumbar joints. Due to motion and stress, the latter constitute a high-risk transitional zone. Pain is transmitted by the posterior branches of the D11, D12 or L1 spinal nerves, which innervate the cutaneous and subcutaneous levels of the low-back and upper buttocks region. It is experienced as a deep-seated pain. Clinical examination makes it possible to determine the level responsible. The lumbar pain disappears with anesthesia of the interapophysary articulation. Appropriate medical treatment most often succeeds. If its fails, surgery can provide a solution. It consists of a capsulectomy on the level responsible, and on the upper and lower adjoining regions. This operation also destroys the posterior branch, which is closely joined to the capsule. Out of the 10 cases operated on, there was 1 failure, 6 very good results and 3 good results after follow-up periods of 20 months to 6 months. Without prejudging the future, it seems that there is hope for the treatment of unexplained back pains or those persisting after operations on lumbar disks that are not relieved by appropriate medical treatment of the thoraco-lumbar joints."} {"id": "PMID:157520", "title": "Non-specific and specific effects of a granulocytic bio-inhibitor on different haematopoietic cell populations.", "content": "The effect of a leucocyte conditioned medium derivative on the 5-125iodo-2'-deoxyuridine (125I-UdR) uptake by 6 haematopoietic cell populations with a simple in vitro assay system was tested. The low doses of the test substance--a putative granulocytic chalone--inhibited significantly the uptake of 125I-UdR only in predominantly granulocytic cell cultures. This inhibition was achieved using micrograms/ml concentrations, which have previously been shown to be inhibitory to normal and malignant granulocytic cells in vivo. The test preparations inhibited the uptake of 125I-UdR in all cell populations (nongranulocytic included) when doses exceeding 10 micrograms/ml were used. The prerequisite for an adequate demonstration of the specificity of a bio-inhibitor is discussed.", "contents": "Non-specific and specific effects of a granulocytic bio-inhibitor on different haematopoietic cell populations. The effect of a leucocyte conditioned medium derivative on the 5-125iodo-2'-deoxyuridine (125I-UdR) uptake by 6 haematopoietic cell populations with a simple in vitro assay system was tested. The low doses of the test substance--a putative granulocytic chalone--inhibited significantly the uptake of 125I-UdR only in predominantly granulocytic cell cultures. This inhibition was achieved using micrograms/ml concentrations, which have previously been shown to be inhibitory to normal and malignant granulocytic cells in vivo. The test preparations inhibited the uptake of 125I-UdR in all cell populations (nongranulocytic included) when doses exceeding 10 micrograms/ml were used. The prerequisite for an adequate demonstration of the specificity of a bio-inhibitor is discussed."} {"id": "PMID:157532", "title": "Biomechanical considerations in the straight-leg-raising test. Cadaveric and clinical studies of the effects of medial hip rotation.", "content": "Studies of the sacral plexus have been made in six cadavers to demonstrate the increased tension due to medial hip rotation. A standard protocol was adopted for the straight-leg-raising test (SLR) and three qualifying tests--dorsiflexion of the ankle, medial hip rotation, and cervical flexion--when examining 442 patients. Positive signs on medial hip rotation were frequently associated with evidence of increased tension and neurologic dysfunction of lumbosacral roots. It is concluded that uncontrolled hip rotation reduces the value of the SLR is a useful qualifying test for increased root tension, and that the diagnostic value and repeatability of SLR would be improved by adopting a standardized protocol.", "contents": "Biomechanical considerations in the straight-leg-raising test. Cadaveric and clinical studies of the effects of medial hip rotation. Studies of the sacral plexus have been made in six cadavers to demonstrate the increased tension due to medial hip rotation. A standard protocol was adopted for the straight-leg-raising test (SLR) and three qualifying tests--dorsiflexion of the ankle, medial hip rotation, and cervical flexion--when examining 442 patients. Positive signs on medial hip rotation were frequently associated with evidence of increased tension and neurologic dysfunction of lumbosacral roots. It is concluded that uncontrolled hip rotation reduces the value of the SLR is a useful qualifying test for increased root tension, and that the diagnostic value and repeatability of SLR would be improved by adopting a standardized protocol."} {"id": "PMID:157533", "title": "Intervertebral disc herniation in the adolescent.", "content": "Twenty-nine patients between 14 and 20 years of age underwent surgical treatment for intervertebral disc herniation over a 10-year period. Trauma was a significant factor in 59%. Back pain was a major complaint in all cases, and all but one had significant sciatic distress. Typical painful, restricted forward flexion was found in 22 cases. All patients had definite signs of nerve root tension. Nerve compression signs were present in 41%. Myelography was done in all cases, and discography was performed on 22 patients to aid in diagnosis and planning of definitive treatment. Twenty-three patients were followed over an average of 5.3 years. Excellent or good results were found in 89%. One patient required a further surgical procedure. Analyzing 12 procedures performed at the L5-S1 level demonstrated excellent results in all patients undergoing lumbosacral fusion combined with discotomy at this level in the presence of a normal L4-5 discogram.", "contents": "Intervertebral disc herniation in the adolescent. Twenty-nine patients between 14 and 20 years of age underwent surgical treatment for intervertebral disc herniation over a 10-year period. Trauma was a significant factor in 59%. Back pain was a major complaint in all cases, and all but one had significant sciatic distress. Typical painful, restricted forward flexion was found in 22 cases. All patients had definite signs of nerve root tension. Nerve compression signs were present in 41%. Myelography was done in all cases, and discography was performed on 22 patients to aid in diagnosis and planning of definitive treatment. Twenty-three patients were followed over an average of 5.3 years. Excellent or good results were found in 89%. One patient required a further surgical procedure. Analyzing 12 procedures performed at the L5-S1 level demonstrated excellent results in all patients undergoing lumbosacral fusion combined with discotomy at this level in the presence of a normal L4-5 discogram."} {"id": "PMID:157540", "title": "Sixty years ago: hospital social work in 1918.", "content": "The year 1918 marked a juncture in the development of social work in health sare. During that year, the fledgling group of hospital social workers responded to needs created by World War I, the influenza pandemic, and epidemics of tuberculosis and venereal disease. At the same time, in order to meet these needs and to professionalize their services, they formed a professional organization, published two new journals, and expanded opportunities for professional education. Examination of these matters helps to explain the place and direction of hospital social work exactly 60 years ago.", "contents": "Sixty years ago: hospital social work in 1918. The year 1918 marked a juncture in the development of social work in health sare. During that year, the fledgling group of hospital social workers responded to needs created by World War I, the influenza pandemic, and epidemics of tuberculosis and venereal disease. At the same time, in order to meet these needs and to professionalize their services, they formed a professional organization, published two new journals, and expanded opportunities for professional education. Examination of these matters helps to explain the place and direction of hospital social work exactly 60 years ago."} {"id": "PMID:157544", "title": "Visceral artery syndromes and reconstructions.", "content": "Acute and chronic visceral ischemia are now well recognized clinical entities and extensive progress has been made in both the evaluation and treatment of patients with these lesions. The visceral vessels and the nature of their collateral pathways can also be of critical importance when dealing with other intra-abdominal pathology. Poor anastomotic healing, or the formation of strictures and intestinal fistulas may result when the mesenteric circulation is slowly compromised. Hence, it is imperative that the visceral arteries, their lesions, and their collateral pathways be understood by all surgeons operating in the abdominal cavity.", "contents": "Visceral artery syndromes and reconstructions. Acute and chronic visceral ischemia are now well recognized clinical entities and extensive progress has been made in both the evaluation and treatment of patients with these lesions. The visceral vessels and the nature of their collateral pathways can also be of critical importance when dealing with other intra-abdominal pathology. Poor anastomotic healing, or the formation of strictures and intestinal fistulas may result when the mesenteric circulation is slowly compromised. Hence, it is imperative that the visceral arteries, their lesions, and their collateral pathways be understood by all surgeons operating in the abdominal cavity."} {"id": "PMID:157557", "title": "Genetic independence of the embryonic reactivity difference to cortisone- and 6-aminonicotinamide-induced cleft palate in the mouse.", "content": "The A/J strain of mice is more reactive than C57BL/6J to both cortisone- and 6-aminonicotinamide-induced cleft palate. A breeding study was set up to determine the genetic control of the differences in embryonic reactivity between the two strains to the two teratogens. In this paper the test for possible association between the two response traits is presented. In the second-backcross generation of embryos where segregation of the two traits could be studied no association was found. Therefore, any embryonic genes making major contributions to differences in reactivity between the two strains are not the same for the two teratogens.", "contents": "Genetic independence of the embryonic reactivity difference to cortisone- and 6-aminonicotinamide-induced cleft palate in the mouse. The A/J strain of mice is more reactive than C57BL/6J to both cortisone- and 6-aminonicotinamide-induced cleft palate. A breeding study was set up to determine the genetic control of the differences in embryonic reactivity between the two strains to the two teratogens. In this paper the test for possible association between the two response traits is presented. In the second-backcross generation of embryos where segregation of the two traits could be studied no association was found. Therefore, any embryonic genes making major contributions to differences in reactivity between the two strains are not the same for the two teratogens."} {"id": "PMID:157558", "title": "Correlation between mandibular retrognathia and induction of cleft palate with 6-aminonicotinamide in the rat.", "content": "A single injection of the niacin antimetabolite 6-aminonicotinamide (6-AN) late in gestation produces cleft palate in the rat. In order to achieve an understanding of the mechanism of induction of cleft palate, craniofacial growth and palate development were studied in Sprague-Dawley rats after treatment with 6-AN on day 15 of gestation. The rats were maintained on a high niacin diet (95 ppm) and subjected to three different teratogenic levels of 6-AN. The first group was injected with 8 mg/kg, the second was fasted and injected with 8 mg/kg and the third was treated with 16 mg/kg. The lowest teratogenic dose, 8 mg/kg, produced mild mandibular retrognathia on day 16, delayed shelf elevation a few hours and resulted in small rostral and small caudal clefts of the secondary palate. The moderate dose, 8 mg/kg with fasting, produced more severe mandibular retrognathia, delayed shelf elevation about 24 hours and resulted in 37% full clefts and 63% partial clefts of the palate. The highest teratogenic dose, 16 mg/kg, produced severe mandibular retrognathia, delayed shelf elevation by more than 24 hours and resulted in 100% full clefts of the palate. In each 6-AN group, the most severe mandibular retrognathia was present between days 16 and 17, the critical time for palate closure in the rat. Treatment with 6-AN also produced abnormality of the epithelial cells of the palate, the toothbuds and the nasal septum. Molar and incisor toothbuds were small and malformed, and the epithelial surfaces of the palate and the soft tissue nasal septum did not fuse.", "contents": "Correlation between mandibular retrognathia and induction of cleft palate with 6-aminonicotinamide in the rat. A single injection of the niacin antimetabolite 6-aminonicotinamide (6-AN) late in gestation produces cleft palate in the rat. In order to achieve an understanding of the mechanism of induction of cleft palate, craniofacial growth and palate development were studied in Sprague-Dawley rats after treatment with 6-AN on day 15 of gestation. The rats were maintained on a high niacin diet (95 ppm) and subjected to three different teratogenic levels of 6-AN. The first group was injected with 8 mg/kg, the second was fasted and injected with 8 mg/kg and the third was treated with 16 mg/kg. The lowest teratogenic dose, 8 mg/kg, produced mild mandibular retrognathia on day 16, delayed shelf elevation a few hours and resulted in small rostral and small caudal clefts of the secondary palate. The moderate dose, 8 mg/kg with fasting, produced more severe mandibular retrognathia, delayed shelf elevation about 24 hours and resulted in 37% full clefts and 63% partial clefts of the palate. The highest teratogenic dose, 16 mg/kg, produced severe mandibular retrognathia, delayed shelf elevation by more than 24 hours and resulted in 100% full clefts of the palate. In each 6-AN group, the most severe mandibular retrognathia was present between days 16 and 17, the critical time for palate closure in the rat. Treatment with 6-AN also produced abnormality of the epithelial cells of the palate, the toothbuds and the nasal septum. Molar and incisor toothbuds were small and malformed, and the epithelial surfaces of the palate and the soft tissue nasal septum did not fuse."} {"id": "PMID:157560", "title": "Changes of adenosine triphosphatase activity in the testes of albino rats under combined influence of low-frequency vibration and intoxication with the herbicide \"Ramrod\".", "content": "The authors follow up the changes of the ATP-ase activity in the testes of albino rats under the influence of Ramrod and low-frequency vibrations, applied separately or in combination. They find that under the influence of a 30-days vibration period upon the gonads of the test animals, there appear changes in the energetic metabolism of a utilizing type, which manifest themselves with an increase of the enzyme activity. The intoxication with Ramrod during four months decreases that activity, whereas through prolongation of the intoxicating period the effect is reverse. The combination of both factors induces a synergetic action which is followed by a considerable increase of the ATP-ase activity.", "contents": "Changes of adenosine triphosphatase activity in the testes of albino rats under combined influence of low-frequency vibration and intoxication with the herbicide \"Ramrod\". The authors follow up the changes of the ATP-ase activity in the testes of albino rats under the influence of Ramrod and low-frequency vibrations, applied separately or in combination. They find that under the influence of a 30-days vibration period upon the gonads of the test animals, there appear changes in the energetic metabolism of a utilizing type, which manifest themselves with an increase of the enzyme activity. The intoxication with Ramrod during four months decreases that activity, whereas through prolongation of the intoxicating period the effect is reverse. The combination of both factors induces a synergetic action which is followed by a considerable increase of the ATP-ase activity."} {"id": "PMID:157561", "title": "Toxicology studies in mice, beagle dogs and rhesus monkeys given chlorozotocin (NSC 178, 248).", "content": "Chlorozotocin was studied for toxic effects in beagle dogs and rhesus monkeys. The results are the subject of this report. The compound was administered i.v. as single and 5 daily doses in dogs and monkeys; and, in dogs, as 10 consecutive daily doses, once weekly for 6 weeks and for 5 daily doses followed by 9 days rest repeated 3 times. The most prominent toxicities in both species were dose-related renal tubular lesions. These appeared as a necrosis at the most toxic levels and a nephrosis at lower doses. The latter change was also seen in animals surviving higher doses but only after a 6-week posttreatment period. Bone marrow hypoplasia and lymphoid atrophy were other common findings at the highest doses in both species. The same general pattern of toxicity appeared in extended treatment studies in dogs, but also included aspermatogenesis. Signs of hepatotoxicity were seen in dogs at the highest dose levels, while monkeys receiving lethal doses also evidenced a toxic gastroenteritis. A single monkey had a diabetic response following 1 treatment with a high non-lethal dose. Renal lesions found in mice following acute, single dose administration were similar to those described for the larger laboratory animals.", "contents": "Toxicology studies in mice, beagle dogs and rhesus monkeys given chlorozotocin (NSC 178, 248). Chlorozotocin was studied for toxic effects in beagle dogs and rhesus monkeys. The results are the subject of this report. The compound was administered i.v. as single and 5 daily doses in dogs and monkeys; and, in dogs, as 10 consecutive daily doses, once weekly for 6 weeks and for 5 daily doses followed by 9 days rest repeated 3 times. The most prominent toxicities in both species were dose-related renal tubular lesions. These appeared as a necrosis at the most toxic levels and a nephrosis at lower doses. The latter change was also seen in animals surviving higher doses but only after a 6-week posttreatment period. Bone marrow hypoplasia and lymphoid atrophy were other common findings at the highest doses in both species. The same general pattern of toxicity appeared in extended treatment studies in dogs, but also included aspermatogenesis. Signs of hepatotoxicity were seen in dogs at the highest dose levels, while monkeys receiving lethal doses also evidenced a toxic gastroenteritis. A single monkey had a diabetic response following 1 treatment with a high non-lethal dose. Renal lesions found in mice following acute, single dose administration were similar to those described for the larger laboratory animals."} {"id": "PMID:157565", "title": "Structural alteration and destructive corneal disease.", "content": "There is good evidence that maintenance of the structural integrity of the human cornea carries with it significant advantages over and above the preservation of normal function. The breakdown in the protective layers of the cornea and invasion by blood vessels and lymphatics would seem to add greatly to the risk of recurrent inflammatory disease. There is a solid rationale, therefore, for the development of therapeutic principles aimed at preventing these structural changes from occurring.", "contents": "Structural alteration and destructive corneal disease. There is good evidence that maintenance of the structural integrity of the human cornea carries with it significant advantages over and above the preservation of normal function. The breakdown in the protective layers of the cornea and invasion by blood vessels and lymphatics would seem to add greatly to the risk of recurrent inflammatory disease. There is a solid rationale, therefore, for the development of therapeutic principles aimed at preventing these structural changes from occurring."} {"id": "PMID:157581", "title": "Von Garrelts' uroflowmeter. A technical evaluation.", "content": "Von Garrelts' uroflowmeter, commercially available, was tested at different true flow rates and jet velocities. The impact geometry was varied. Results show that flow-rate recording with von Garrelts' uroflowmeter is little influenced by variations of these parameters, and the instrument can be recommended for scientific and routine clinical use.", "contents": "Von Garrelts' uroflowmeter. A technical evaluation. Von Garrelts' uroflowmeter, commercially available, was tested at different true flow rates and jet velocities. The impact geometry was varied. Results show that flow-rate recording with von Garrelts' uroflowmeter is little influenced by variations of these parameters, and the instrument can be recommended for scientific and routine clinical use."} {"id": "PMID:157582", "title": "[The controlled TUR. Hydraulic stimulation of the external sphincter (author's transl)].", "content": "The demonstration of contractions of the external sphincter muscle is of good help for orientation in all transurethral resections of the bladder neck. A simple and reliable procedure is described producing contractions of the external sphincter muscle by hydraulic stimulation. This is achieved by sudden and repeated stop and flow of the irrigation fluid.", "contents": "[The controlled TUR. Hydraulic stimulation of the external sphincter (author's transl)]. The demonstration of contractions of the external sphincter muscle is of good help for orientation in all transurethral resections of the bladder neck. A simple and reliable procedure is described producing contractions of the external sphincter muscle by hydraulic stimulation. This is achieved by sudden and repeated stop and flow of the irrigation fluid."} {"id": "PMID:157583", "title": "Siblings with prune belly syndrome and associated pulmonic stenosis, mental retardation, and deafness.", "content": "This is the fifth family in the literature with siblings having the prune belly syndrome. It is the first with associated pulmonary stenosis, mental retardation, and hearing deficit. A genetic factor is suggested as the primary cause of the syndrome.", "contents": "Siblings with prune belly syndrome and associated pulmonic stenosis, mental retardation, and deafness. This is the fifth family in the literature with siblings having the prune belly syndrome. It is the first with associated pulmonary stenosis, mental retardation, and hearing deficit. A genetic factor is suggested as the primary cause of the syndrome."} {"id": "PMID:157580", "title": "[Activation of plasminogen in its immobilization].", "content": "Plasminogen is established to be able of transforming into the plasmin-like is compound when it is immobilized on aminoethyl cellulose by means of glutaric aldehyde. The plasminogen immobilized in such a way manifests a caseinolytic activity and is not activated additionally by streptokinase. The plasminogen immobilized on bromocyanogen-activated sepharose and cellulose, like soluble proenzyme, has no activity of plasmin and retains the ability of being activated with streptokinase in catalytic amounts.", "contents": "[Activation of plasminogen in its immobilization]. Plasminogen is established to be able of transforming into the plasmin-like is compound when it is immobilized on aminoethyl cellulose by means of glutaric aldehyde. The plasminogen immobilized in such a way manifests a caseinolytic activity and is not activated additionally by streptokinase. The plasminogen immobilized on bromocyanogen-activated sepharose and cellulose, like soluble proenzyme, has no activity of plasmin and retains the ability of being activated with streptokinase in catalytic amounts."} {"id": "PMID:157585", "title": "Studies on the epidemiology of bovine parasitic bronchitis.", "content": "In the West of Scotland the epidemiology of parasitic bronchitis in grazing calves was studied over a two year period with the aid of tracer calves and herbage examinations for Dictyocaulus viviparus larvae. The observations of both years emphasised the importance of overwintered lungworm larvae as a source of disease. In the first year it was shown that the ingestion and development of these overwintered larvae were, by themselves, directly responsible for severe morbidity, high faecal larval counts and deaths. In the second year it was shown that pasture ungrazed during the winter and spring and from which a hay crop was removed in mid-summer was still capable of producing clinical parasitic bronchitis in susceptible calves within three to four weeks of their introduction in later summer. In both years there was some evidence that the outbreaks appeared to be associated with the sudden availability of infective larvae on the herbage. The possibility that such larvae may have survived for many months in the soil is discussed. Despite the heavy challenge with lungworm larvae experienced by the grazing calves in the first year those vaccinated with lungworm vaccine survived, their clinical signs were mild and of short duration and their faecal larval output was greatly reduced.", "contents": "Studies on the epidemiology of bovine parasitic bronchitis. In the West of Scotland the epidemiology of parasitic bronchitis in grazing calves was studied over a two year period with the aid of tracer calves and herbage examinations for Dictyocaulus viviparus larvae. The observations of both years emphasised the importance of overwintered lungworm larvae as a source of disease. In the first year it was shown that the ingestion and development of these overwintered larvae were, by themselves, directly responsible for severe morbidity, high faecal larval counts and deaths. In the second year it was shown that pasture ungrazed during the winter and spring and from which a hay crop was removed in mid-summer was still capable of producing clinical parasitic bronchitis in susceptible calves within three to four weeks of their introduction in later summer. In both years there was some evidence that the outbreaks appeared to be associated with the sudden availability of infective larvae on the herbage. The possibility that such larvae may have survived for many months in the soil is discussed. Despite the heavy challenge with lungworm larvae experienced by the grazing calves in the first year those vaccinated with lungworm vaccine survived, their clinical signs were mild and of short duration and their faecal larval output was greatly reduced."} {"id": "PMID:157586", "title": "Efficacy of oxfendazole against natural infestations of nematodes and cestodes in sheep in Egypt.", "content": "Oxfendazole liquid suspension (Systamex; Wellcome) was administered orally at the dose of 4.5 mg per kg to 800 indigenous Egyptian sheep clinically affected with Dictyocaulus filaria, Moniezia expansa, Haemonchus contortus, Ostertagia circumcincta, Nematodirus spp, Trichostrongylus axei, Cooperia curticei, Trichuris ovis and Oesophagostomum spp. A 100 per cent clearance was recorded for all parasites with the exception of T ovis which were markedly reduced in number.", "contents": "Efficacy of oxfendazole against natural infestations of nematodes and cestodes in sheep in Egypt. Oxfendazole liquid suspension (Systamex; Wellcome) was administered orally at the dose of 4.5 mg per kg to 800 indigenous Egyptian sheep clinically affected with Dictyocaulus filaria, Moniezia expansa, Haemonchus contortus, Ostertagia circumcincta, Nematodirus spp, Trichostrongylus axei, Cooperia curticei, Trichuris ovis and Oesophagostomum spp. A 100 per cent clearance was recorded for all parasites with the exception of T ovis which were markedly reduced in number."} {"id": "PMID:157590", "title": "Lungworm: (Dictyocaulus arnfieldi) infection in donkeys.", "content": "The clinical, parasitological and pathological findings in a group of six donkeys naturally infected with D arnfieldi larvae are described. One animal had to be sacrificed at an early date because it developed pneumonia. The remaining five were unthrifty, showed mild clinical respiratory signs and had heavy strongyle infections. They had varying numbers of adult worms in the airways of the lungs and eggs were found coiled up in the smaller bronchi where they had apparently lead to an obstruction to airflow in that segment. The most striking gross pathological changes were circular discrete areas of over-inflation surrounding such bronchi. Histologically the infected bronchi exhibited a marked bronchiolitis with goblet cell hyperplasia and a mainly lymphoid inflammatory infiltrate. These areas also showed a localised bronchiolitus and overinflated alveolar tissue although true emphysema was not present. It is postulated that the parasite is well-adapted to its host and is able to survive for long periods within the lung without causing a debilitating amount of damage to the host. The immunological aspects of the infection are discussed briefly.", "contents": "Lungworm: (Dictyocaulus arnfieldi) infection in donkeys. The clinical, parasitological and pathological findings in a group of six donkeys naturally infected with D arnfieldi larvae are described. One animal had to be sacrificed at an early date because it developed pneumonia. The remaining five were unthrifty, showed mild clinical respiratory signs and had heavy strongyle infections. They had varying numbers of adult worms in the airways of the lungs and eggs were found coiled up in the smaller bronchi where they had apparently lead to an obstruction to airflow in that segment. The most striking gross pathological changes were circular discrete areas of over-inflation surrounding such bronchi. Histologically the infected bronchi exhibited a marked bronchiolitis with goblet cell hyperplasia and a mainly lymphoid inflammatory infiltrate. These areas also showed a localised bronchiolitus and overinflated alveolar tissue although true emphysema was not present. It is postulated that the parasite is well-adapted to its host and is able to survive for long periods within the lung without causing a debilitating amount of damage to the host. The immunological aspects of the infection are discussed briefly."} {"id": "PMID:157591", "title": "Efficacy of mebendazole against Dictyocaulus arnfieldi in the donkey.", "content": "In a controlled trial in naturally infected donkeys the efficacy of mebendazole against Dictyocaulus arnfieldi infection was evaluated. A powder formulation of mebendazole given orally at a dosage rate of 4.3 to 5.7 mg per kg per day for five days had no apparent effect on existing lungworm burdens. However a paste formulation of mebendazole given orally at a higher dosage rate of 15.2 to 20.0 mg per kg per day for five days was 75 to 100 per cent effective in the removal of lungworms from individual animals.", "contents": "Efficacy of mebendazole against Dictyocaulus arnfieldi in the donkey. In a controlled trial in naturally infected donkeys the efficacy of mebendazole against Dictyocaulus arnfieldi infection was evaluated. A powder formulation of mebendazole given orally at a dosage rate of 4.3 to 5.7 mg per kg per day for five days had no apparent effect on existing lungworm burdens. However a paste formulation of mebendazole given orally at a higher dosage rate of 15.2 to 20.0 mg per kg per day for five days was 75 to 100 per cent effective in the removal of lungworms from individual animals."} {"id": "PMID:157592", "title": "The relationship between extracellular matrix vesicles and calcospherities in primary mineralization of neoplastic bone tissue. TEM and SEM studies on osteosarcoma.", "content": "Primary mineralization in neoplastic tissue was studied in osteosarcoma, correlating observations obtained by SEM to those found with TEM. The process is characterized by extracellular matrix vesicles, distributed in the matrix between the forming neoplastic cells and the calcifying fronts. The occurrence of osmiophilic material and solitary hydroxyapatite crystals within the vesicles is followed by accumulation of apatite crystals, disappearance of the vesicular membrane and formation of calcospherites and calcified fronts. The process described here in neoplastic tissue is essentially similar to primary calcification in normal calcified tissues.", "contents": "The relationship between extracellular matrix vesicles and calcospherities in primary mineralization of neoplastic bone tissue. TEM and SEM studies on osteosarcoma. Primary mineralization in neoplastic tissue was studied in osteosarcoma, correlating observations obtained by SEM to those found with TEM. The process is characterized by extracellular matrix vesicles, distributed in the matrix between the forming neoplastic cells and the calcifying fronts. The occurrence of osmiophilic material and solitary hydroxyapatite crystals within the vesicles is followed by accumulation of apatite crystals, disappearance of the vesicular membrane and formation of calcospherites and calcified fronts. The process described here in neoplastic tissue is essentially similar to primary calcification in normal calcified tissues."} {"id": "PMID:157594", "title": "Pulmonary infection with capsule-deficient cryptococcus neoformans.", "content": "A case of bilateral lobar pneumonia due to Crytococcus neoformans is presented. The capsule-deficient fungal organisms within tissue were suggestive of Histoplasma capsulatum. Cultures grew Cryptococcus neoformans and there was cryptococcal antigen in the serum. Pulmonary cryptococcosis and the occurrence of unencapsulated cryptococci are reviewed. The important role both culture and the latex agglutination test for cryptococcal antigen play in the differential diagnosis of systemic fungal infections with over-lapping histopathology are discussed.", "contents": "Pulmonary infection with capsule-deficient cryptococcus neoformans. A case of bilateral lobar pneumonia due to Crytococcus neoformans is presented. The capsule-deficient fungal organisms within tissue were suggestive of Histoplasma capsulatum. Cultures grew Cryptococcus neoformans and there was cryptococcal antigen in the serum. Pulmonary cryptococcosis and the occurrence of unencapsulated cryptococci are reviewed. The important role both culture and the latex agglutination test for cryptococcal antigen play in the differential diagnosis of systemic fungal infections with over-lapping histopathology are discussed."} {"id": "PMID:157595", "title": "Phagocytosis of chromium during patellar osteoarthritic remodelling associated with a knee prosthesis.", "content": "The report is of an anatomico-pathological and electron probe microanalyzer study of a patella with osteoarthritic remodelling, that had been in contact with a cast cobalt-chromium-molybdenum prosthesis for two years and seven months. Abrasion of the metal resulted in preferential phagocytosis of chromium, principally in the wall of an osteoarthritis cyst. This observation indicates that a substance administered by intra-articular pathway for the treatment of osteoarthritis can become phagocytosed, and quite deeply, in the remodelled bone.", "contents": "Phagocytosis of chromium during patellar osteoarthritic remodelling associated with a knee prosthesis. The report is of an anatomico-pathological and electron probe microanalyzer study of a patella with osteoarthritic remodelling, that had been in contact with a cast cobalt-chromium-molybdenum prosthesis for two years and seven months. Abrasion of the metal resulted in preferential phagocytosis of chromium, principally in the wall of an osteoarthritis cyst. This observation indicates that a substance administered by intra-articular pathway for the treatment of osteoarthritis can become phagocytosed, and quite deeply, in the remodelled bone."} {"id": "PMID:157596", "title": "Orcein positive granules in the hepatocytes in chronic intrahepatic cholestasis. Morphological, histochemical and electron X-ray microanalytical examination.", "content": "The morphological characteristics of orcein positive granules in hepatocytes from 11 patients with chronic intrahepatic cholestasis and from 2 newborn normal livers were studied. Histochemical investigations revealed their protein nature and many sulphydryl and/or disulphide groups. Copper was demonstrated in the granules by histochemical techniques and electron X-ray micronalysis. No difference was observed in the hepatic distribution and appearance of the granules between the livers of those with chronic cholestasis and the newborn. Ultrastructurally, a variety of electron dense granules were seen at the site of orcein positive granules in the hepatocytes of the patient with primary biliary cirrhosis. Some had a single-layered membrane and seem to be lysosomal derivatives. It is suggested that the copper in lysosomes seen in both chronic cholestasis and normal newborn livers, need not to be cytotoxic.", "contents": "Orcein positive granules in the hepatocytes in chronic intrahepatic cholestasis. Morphological, histochemical and electron X-ray microanalytical examination. The morphological characteristics of orcein positive granules in hepatocytes from 11 patients with chronic intrahepatic cholestasis and from 2 newborn normal livers were studied. Histochemical investigations revealed their protein nature and many sulphydryl and/or disulphide groups. Copper was demonstrated in the granules by histochemical techniques and electron X-ray micronalysis. No difference was observed in the hepatic distribution and appearance of the granules between the livers of those with chronic cholestasis and the newborn. Ultrastructurally, a variety of electron dense granules were seen at the site of orcein positive granules in the hepatocytes of the patient with primary biliary cirrhosis. Some had a single-layered membrane and seem to be lysosomal derivatives. It is suggested that the copper in lysosomes seen in both chronic cholestasis and normal newborn livers, need not to be cytotoxic."} {"id": "PMID:157597", "title": "Course and spontaneous regression of acute pancreatitis in the rat.", "content": "Rat exocrine pancreatic function was studied structurally and biochemically after the in vivo production of actue interstitial pancreatitis by supramaximal stimulation with caerulein. Two major phases in the reaction of the gland were observed: During the first two days after cessation of the supramaximal stimulation a progressive infiltration of the interstitium and the pancreatic tissue with polymorphonuclear leucocytes, lymphocytes and macrophages occurred which led to further destruction of the gland and to decreased functional response. From two days after the cessation of the treatment, hypertrophy of centro-acinar cells and an increased rate of mitotic activity indicated regeneration of the pancreas. This was combined with an accelerated in vitro discharge of newly synthesized proteins over a period of four days. Between days three and six after the initial treatment mitotic activity was also observed in fully differentiated exocrine cells. Total structural and functional recovery of the pancreas was achieved nine to tweleve days after the cessation of the supramaximal stimulation.", "contents": "Course and spontaneous regression of acute pancreatitis in the rat. Rat exocrine pancreatic function was studied structurally and biochemically after the in vivo production of actue interstitial pancreatitis by supramaximal stimulation with caerulein. Two major phases in the reaction of the gland were observed: During the first two days after cessation of the supramaximal stimulation a progressive infiltration of the interstitium and the pancreatic tissue with polymorphonuclear leucocytes, lymphocytes and macrophages occurred which led to further destruction of the gland and to decreased functional response. From two days after the cessation of the treatment, hypertrophy of centro-acinar cells and an increased rate of mitotic activity indicated regeneration of the pancreas. This was combined with an accelerated in vitro discharge of newly synthesized proteins over a period of four days. Between days three and six after the initial treatment mitotic activity was also observed in fully differentiated exocrine cells. Total structural and functional recovery of the pancreas was achieved nine to tweleve days after the cessation of the supramaximal stimulation."} {"id": "PMID:157598", "title": "Kidney tubule basement membrane alterations in type II membranoproliferative glomerulonephritis.", "content": "Fourteen kidney biopsy specimens from nine patients with type II membranoproliferative glomerulonephritis (MPGN) were examined by electron microscopy for tubular basement membrane (TBM) alterations. In all biopsies, laminal densities, charateristic for type II MPGN, were present in the glomerular basement membranes. The TBM alterations observed included: 1) the presence of laminal, and/or discrete, and/or aggregated densities; 2)focal thickening; 3) multilamination; and, 4) vesicular structures. Laminal densities occurred in 6 of the 9 cases examined. All biopsies had TBM densities representative of at least one of the three forms. The occurrence of electron densities in or near the TBM in type II MPGN may have diagnostic value. In those biopsies where tissue is insufficient for immunofluorescence microscopy and where glomeruli are not found on electron microscopy, an electron microscopic search for densities associated with TBMs would be warranted. Although TBM-associated densities are not pathognomonic for type II MPGN, the observation of such densities, espically laminal densities, would be useful in complementing light miccrscopic and clinical findings.", "contents": "Kidney tubule basement membrane alterations in type II membranoproliferative glomerulonephritis. Fourteen kidney biopsy specimens from nine patients with type II membranoproliferative glomerulonephritis (MPGN) were examined by electron microscopy for tubular basement membrane (TBM) alterations. In all biopsies, laminal densities, charateristic for type II MPGN, were present in the glomerular basement membranes. The TBM alterations observed included: 1) the presence of laminal, and/or discrete, and/or aggregated densities; 2)focal thickening; 3) multilamination; and, 4) vesicular structures. Laminal densities occurred in 6 of the 9 cases examined. All biopsies had TBM densities representative of at least one of the three forms. The occurrence of electron densities in or near the TBM in type II MPGN may have diagnostic value. In those biopsies where tissue is insufficient for immunofluorescence microscopy and where glomeruli are not found on electron microscopy, an electron microscopic search for densities associated with TBMs would be warranted. Although TBM-associated densities are not pathognomonic for type II MPGN, the observation of such densities, espically laminal densities, would be useful in complementing light miccrscopic and clinical findings."} {"id": "PMID:157599", "title": "Bone modelling processes at the endosteal surface of human femora. Scanning electron microscopical studies in normal bone and in renal osteodystrophy.", "content": "In femoral bone of 10 adult patients without bone disease and of 15 patients with secondary hyperparathyroidism, thy after nonmineralised organic material had been removed from the endosteal surface by sodium hypochlorite. This technique permits one to analyse the effects of past osteoblastic and osteoclastic activities. Im normal bone, the endosteal envelope shows a highly ordered texture: The main part of the inner surface is represented by fully mineralised smooth surfaces without evidence of apposition or resorption (so called neutral surfaces). In apposition areas, collagen fibers are still incompletely mineralised. Ordered mineral deposits are observed, consisting of spindleshaped calcospherites of uniform size. The resorption areas are sharply delimited. The resorption layer shows a small difference of level with respect to the surrounding neutral surface. Resorption areas consist of numerous lacunae with a smooth bottom. Individual lacunae are encircled by shallow ridges which run almost perpendicularly to the main direction of collagen fibers that have been exposed by resorption. These findings suggest that in normal bone osteoclasts act as a corrdinated group of cells. The direction of advance of the resorption area is to some extent influenced by the collagen pattern of bone. In patients with secondary hyperparathyroidism, domain formation of the endosteal surface can no longer be recognized. The size and shape of caleospherites are extremely heterogeneous, a finding interpreted as evidence of formation of woven bone. Resorption areas are irregularly determined and often resemble worm-eaten wood. The planes of resorption vary in direction and depth and in general resorption cavities penetrate deeper than in normal bone. These findings point to loss of coordinated cell action under the influence of hyperparathyroidism. The observations suggest that in hyperparathyroidism endosteal cells do not respond to local factors which influence endosteal cell activities in modelling processes of normal bone. Such local factors consist of the pattern of collagen andlamellar organisation on one hand and mechanical forces presumably via pizo-electrical potentials, on the other. In hyperparathyroidism the interdependence between bone matrix texture and spatial orientation of bone surface lining cell activities is lost.", "contents": "Bone modelling processes at the endosteal surface of human femora. Scanning electron microscopical studies in normal bone and in renal osteodystrophy. In femoral bone of 10 adult patients without bone disease and of 15 patients with secondary hyperparathyroidism, thy after nonmineralised organic material had been removed from the endosteal surface by sodium hypochlorite. This technique permits one to analyse the effects of past osteoblastic and osteoclastic activities. Im normal bone, the endosteal envelope shows a highly ordered texture: The main part of the inner surface is represented by fully mineralised smooth surfaces without evidence of apposition or resorption (so called neutral surfaces). In apposition areas, collagen fibers are still incompletely mineralised. Ordered mineral deposits are observed, consisting of spindleshaped calcospherites of uniform size. The resorption areas are sharply delimited. The resorption layer shows a small difference of level with respect to the surrounding neutral surface. Resorption areas consist of numerous lacunae with a smooth bottom. Individual lacunae are encircled by shallow ridges which run almost perpendicularly to the main direction of collagen fibers that have been exposed by resorption. These findings suggest that in normal bone osteoclasts act as a corrdinated group of cells. The direction of advance of the resorption area is to some extent influenced by the collagen pattern of bone. In patients with secondary hyperparathyroidism, domain formation of the endosteal surface can no longer be recognized. The size and shape of caleospherites are extremely heterogeneous, a finding interpreted as evidence of formation of woven bone. Resorption areas are irregularly determined and often resemble worm-eaten wood. The planes of resorption vary in direction and depth and in general resorption cavities penetrate deeper than in normal bone. These findings point to loss of coordinated cell action under the influence of hyperparathyroidism. The observations suggest that in hyperparathyroidism endosteal cells do not respond to local factors which influence endosteal cell activities in modelling processes of normal bone. Such local factors consist of the pattern of collagen andlamellar organisation on one hand and mechanical forces presumably via pizo-electrical potentials, on the other. In hyperparathyroidism the interdependence between bone matrix texture and spatial orientation of bone surface lining cell activities is lost."} {"id": "PMID:157600", "title": "A new, simple method for intraoperative fast diagnosis.", "content": "The suitability of stain-coated, ready-to-use slides (Testsimplets) for routine staining of intraoperative imprint-cytology preparations is discussed. The microscopic preparations are easily and quickly prepared, may be evaluated immediately and, with a slight loss of quality, may be kept for up to a week after application of paraffin to the cover glass. This method produces interpretable slides from cell-rich benign and malignant tumors. It is by no means a complete substitute for the usual fast-section techniques, but may be used in order to save time.", "contents": "A new, simple method for intraoperative fast diagnosis. The suitability of stain-coated, ready-to-use slides (Testsimplets) for routine staining of intraoperative imprint-cytology preparations is discussed. The microscopic preparations are easily and quickly prepared, may be evaluated immediately and, with a slight loss of quality, may be kept for up to a week after application of paraffin to the cover glass. This method produces interpretable slides from cell-rich benign and malignant tumors. It is by no means a complete substitute for the usual fast-section techniques, but may be used in order to save time."} {"id": "PMID:157602", "title": "Rat liver alterations after chronic treatment with hexachlorobenzene.", "content": "Groups of female rats were treated orally with 0.5, 2.0, 8.0, and 32 mg/kg hexachlorobenzene twice a week for 203 days. The liver content of hexachlorobenzene was found to be dose-dependent. In the animals treated with the highest dose the concentration was 273 mug/g hexachlorobenzene. In the fresh and fixed hepatic tissue of the treated animals pink fluorescence was observed. Electron microscopy revealed a dose dependent enlargement of all hepatocytes due to proliferation of the SER in the centrolobular area or to increased glycogen deposits (beta- or alpha-particles) and SER in the intermediary and periportal area. Numerous porphyrin deposits and siderosomes, intimate disorganisation and moderate dislocation of the RER and a moderate enlargement of bizarre-sharped mitochondria were recognized. The relationship between porphyrin crystals and mitochondria on the one hand and between SER and glycogen deposits on the other is discussed.", "contents": "Rat liver alterations after chronic treatment with hexachlorobenzene. Groups of female rats were treated orally with 0.5, 2.0, 8.0, and 32 mg/kg hexachlorobenzene twice a week for 203 days. The liver content of hexachlorobenzene was found to be dose-dependent. In the animals treated with the highest dose the concentration was 273 mug/g hexachlorobenzene. In the fresh and fixed hepatic tissue of the treated animals pink fluorescence was observed. Electron microscopy revealed a dose dependent enlargement of all hepatocytes due to proliferation of the SER in the centrolobular area or to increased glycogen deposits (beta- or alpha-particles) and SER in the intermediary and periportal area. Numerous porphyrin deposits and siderosomes, intimate disorganisation and moderate dislocation of the RER and a moderate enlargement of bizarre-sharped mitochondria were recognized. The relationship between porphyrin crystals and mitochondria on the one hand and between SER and glycogen deposits on the other is discussed."} {"id": "PMID:157603", "title": "The ultrastructure of the various forms of pulmonary arterial intimal fibrosis.", "content": "Intimal fibrosis of muscular pulmonary arteries may present in various forms and in varying degrees of severity according to the underlying condition. In patients with pulmonary hypertension, the type of initimal fibrosis is often significant with regard to prognosis and reversibility. For these reasons we have studied the ultrastructure of the thickened intimal layer in aged individuals, where intimal fibrosis occurs as a normal age change, and in patients with pulmonary hypertension associated with fibrosis of the lungs, mitral stenosis, chronic pulmonary thromboembolism and plexogenic pulmonary arteriopathy (either primary or secondary to congenital cardiac defects). In all these forms of intimal fibrosis, the cellular component of the subendothelial intimal layer was apparently almost exclusively the smooth muscle cell. The cells usually had a haphazard arrangement. In primary and secondary plexogenic pulmonary arteriopathy, however, there was a more regular circumferential arrangement. The ultrastructural evidence suggested that the intimal cells were derived from medial smooth muscle cells.", "contents": "The ultrastructure of the various forms of pulmonary arterial intimal fibrosis. Intimal fibrosis of muscular pulmonary arteries may present in various forms and in varying degrees of severity according to the underlying condition. In patients with pulmonary hypertension, the type of initimal fibrosis is often significant with regard to prognosis and reversibility. For these reasons we have studied the ultrastructure of the thickened intimal layer in aged individuals, where intimal fibrosis occurs as a normal age change, and in patients with pulmonary hypertension associated with fibrosis of the lungs, mitral stenosis, chronic pulmonary thromboembolism and plexogenic pulmonary arteriopathy (either primary or secondary to congenital cardiac defects). In all these forms of intimal fibrosis, the cellular component of the subendothelial intimal layer was apparently almost exclusively the smooth muscle cell. The cells usually had a haphazard arrangement. In primary and secondary plexogenic pulmonary arteriopathy, however, there was a more regular circumferential arrangement. The ultrastructural evidence suggested that the intimal cells were derived from medial smooth muscle cells."} {"id": "PMID:157605", "title": "Purification of human intestinal goblet cell antigen (GOA), its immunohistological demonstration in the intestine and in mucus producing gastrointestinal adenocarcinomas.", "content": "Goblet cell antigen (GOA) was purified from gastric signet ring cell carcinoma. It was immunogenic and was used to produced antisera which stained goblet cells of the small and large intestine and of intestinalized gastric mucosa by indirect immunological methods. Various types of gastric and colonic cancer contained GOA. These findings demonstrate a histiogenic relationship between intestinal goblet cells, various gastrointestinal cancers and associated premalignant conditions.", "contents": "Purification of human intestinal goblet cell antigen (GOA), its immunohistological demonstration in the intestine and in mucus producing gastrointestinal adenocarcinomas. Goblet cell antigen (GOA) was purified from gastric signet ring cell carcinoma. It was immunogenic and was used to produced antisera which stained goblet cells of the small and large intestine and of intestinalized gastric mucosa by indirect immunological methods. Various types of gastric and colonic cancer contained GOA. These findings demonstrate a histiogenic relationship between intestinal goblet cells, various gastrointestinal cancers and associated premalignant conditions."} {"id": "PMID:157606", "title": "Extensive hepatic cell necrosis produced by the Shwartzman mechanism.", "content": "Acute, severe, and extensive necrosis of the liver was produced in pregnant and non-pregnant female adult rabbits by the Shwartzman mechanism. Shwartzman reagent (E. coli endotoxin) was administered in various combinations by three routes of injection, the portal vein (mesenteric vein), the bile duct, and the ear vein. Morphologic changes of the extrahepatic organs were minimal. The similarity to massive necrosis in human liver and the effect of pregnancy on hepatic necrosis in rabbit and man were discussed. The lesion is presented as a new animal model for acute massive hepatic necrosis and is proposed as a third category of Shwartzman reaction, designated the univisceral type.", "contents": "Extensive hepatic cell necrosis produced by the Shwartzman mechanism. Acute, severe, and extensive necrosis of the liver was produced in pregnant and non-pregnant female adult rabbits by the Shwartzman mechanism. Shwartzman reagent (E. coli endotoxin) was administered in various combinations by three routes of injection, the portal vein (mesenteric vein), the bile duct, and the ear vein. Morphologic changes of the extrahepatic organs were minimal. The similarity to massive necrosis in human liver and the effect of pregnancy on hepatic necrosis in rabbit and man were discussed. The lesion is presented as a new animal model for acute massive hepatic necrosis and is proposed as a third category of Shwartzman reaction, designated the univisceral type."} {"id": "PMID:157607", "title": "Muscle spindles in rheumatoid arthritis. An ultrastructural study.", "content": "Ultrastructural features of muscle spindles were studied in biopsy material from 100 patients suffering from classical rheumatoid arthritis. Thickening of the outer capsule, increased amount of extracellular ground substance within the inner capsule, and marked thickening of the basement membrane of capillary blood vessels supplying the muscle spindles were observed. Chronic inflammatory cells and macrophages were present within the spindles. Changes affecting the intrafusal muscle fibres were also seen. They were manifest as atrophy and degeneration of the intrafusal muscle fibres, absence of the specialised junctional complexes, and of the intercellular bridges, microladders and satellite cells. It is suggested that the changes affecting the intrafusal muscle fibres are probably secondary. Damage to the myelinated nerves was present, while the sensory and motor nerve endings were well preserved.", "contents": "Muscle spindles in rheumatoid arthritis. An ultrastructural study. Ultrastructural features of muscle spindles were studied in biopsy material from 100 patients suffering from classical rheumatoid arthritis. Thickening of the outer capsule, increased amount of extracellular ground substance within the inner capsule, and marked thickening of the basement membrane of capillary blood vessels supplying the muscle spindles were observed. Chronic inflammatory cells and macrophages were present within the spindles. Changes affecting the intrafusal muscle fibres were also seen. They were manifest as atrophy and degeneration of the intrafusal muscle fibres, absence of the specialised junctional complexes, and of the intercellular bridges, microladders and satellite cells. It is suggested that the changes affecting the intrafusal muscle fibres are probably secondary. Damage to the myelinated nerves was present, while the sensory and motor nerve endings were well preserved."} {"id": "PMID:157608", "title": "The fine structure of meningiomas: an attempted classification.", "content": "We examined 23 meningiomas by electron microscopy. In each case it was possible to distinguish certain cells with epithelial features (desmosomes, microfliaments, interdigitating extensions) and others with fibroblastic features (collagen fibers). Others cells of transitional form were also seen. The proportion of these cellular types is variable, making it possible to classify meningiomas into seven types of progressing gradually from a purely epithelial type to a purely fibroblastic one.-We found no important ultrastructural abnormalities in the cells. These case reports confirm the uniqueness of meningiomas, which are composed of variously shaped cells but have their origin from a single cellular type. This has double potentiality for fibroblastic and epithelial differentiation.", "contents": "The fine structure of meningiomas: an attempted classification. We examined 23 meningiomas by electron microscopy. In each case it was possible to distinguish certain cells with epithelial features (desmosomes, microfliaments, interdigitating extensions) and others with fibroblastic features (collagen fibers). Others cells of transitional form were also seen. The proportion of these cellular types is variable, making it possible to classify meningiomas into seven types of progressing gradually from a purely epithelial type to a purely fibroblastic one.-We found no important ultrastructural abnormalities in the cells. These case reports confirm the uniqueness of meningiomas, which are composed of variously shaped cells but have their origin from a single cellular type. This has double potentiality for fibroblastic and epithelial differentiation."} {"id": "PMID:157609", "title": "Ultrastructural observations on axonal swelling in the human gracile nucleus.", "content": "The morphology of the spheroids in human gracile nuclei was studied by light and electron microscopy. Various spheroids encountered in the present study could be classified into three types based on the internal structure: The first one was chiefly composed of many irregular homogeneous dense bodies, multivesicular bodies seemed to deposit multicentrically in an axon in the early stage of \"ballon\" formation and coalesce to form larger ones. The second was characterized by a marked accumulated of closely approximated mitochondria and dense concentric bodies. In the third the most characteristic findings were neurofibrillary accumulation and aggregations of dense bodies. These findings showed some divergence from those of dystrophic axons and the last two mimic those of degenerative or regenerative axons, which suggested that axonal swelling (including dystrophic axon) is not characteristic reaction of specific disease but rather nonspecific one to a variety of noxious stimuli. With light microscope, it was difficult to distinguish balloons with different structures since they were quite diverse and manifold in their shape, size, appearance and stainability. Intra-axonal corpora amylacea were seen in most cases and their incidence appeared to be nonspecific for any diseases.", "contents": "Ultrastructural observations on axonal swelling in the human gracile nucleus. The morphology of the spheroids in human gracile nuclei was studied by light and electron microscopy. Various spheroids encountered in the present study could be classified into three types based on the internal structure: The first one was chiefly composed of many irregular homogeneous dense bodies, multivesicular bodies seemed to deposit multicentrically in an axon in the early stage of \"ballon\" formation and coalesce to form larger ones. The second was characterized by a marked accumulated of closely approximated mitochondria and dense concentric bodies. In the third the most characteristic findings were neurofibrillary accumulation and aggregations of dense bodies. These findings showed some divergence from those of dystrophic axons and the last two mimic those of degenerative or regenerative axons, which suggested that axonal swelling (including dystrophic axon) is not characteristic reaction of specific disease but rather nonspecific one to a variety of noxious stimuli. With light microscope, it was difficult to distinguish balloons with different structures since they were quite diverse and manifold in their shape, size, appearance and stainability. Intra-axonal corpora amylacea were seen in most cases and their incidence appeared to be nonspecific for any diseases."} {"id": "PMID:157610", "title": "Maglignant giant cell tumor of tendon sheath.", "content": "A benign, but aggressive, giant cell tumor of tendon sheath developed over a period of 20 years into a metasasizing, histologiclly malignant giant cell tumor. Ultrastructure of the malignant tumor showed the same five cell types as described in giant cell tumors of tendon sheath. Even the same crystals were identified in the osteoblast-like and osteoclast-like cells. It therefore appears reasonable to assume that giant cell tumors of tendon sheath indeed are neoplasms with a malignant potential and not an inflammatory with partial osseous differentiation. No ultrastructural similarities with fibrous histiocytoma were apparent.", "contents": "Maglignant giant cell tumor of tendon sheath. A benign, but aggressive, giant cell tumor of tendon sheath developed over a period of 20 years into a metasasizing, histologiclly malignant giant cell tumor. Ultrastructure of the malignant tumor showed the same five cell types as described in giant cell tumors of tendon sheath. Even the same crystals were identified in the osteoblast-like and osteoclast-like cells. It therefore appears reasonable to assume that giant cell tumors of tendon sheath indeed are neoplasms with a malignant potential and not an inflammatory with partial osseous differentiation. No ultrastructural similarities with fibrous histiocytoma were apparent."} {"id": "PMID:157612", "title": "Malignant Schwannoma associated with von Recklinghausen's neurofibromatosis.", "content": "A series of 46 malignant schwannomas occurring in soft parts of patients having von Recklinghausen's neurofibromatosis was analyzed. The diagnosis of malignant schwannoma was based upon the occurrence of malignant spindled cells closely resembling Schwann cells in the neoplasm and the close association or origin of the malignant schwannoma in a neurofibroma (27 tumors), or a large peripheral nerve (31 tumors). Additional histologic features useful in making the diagnosis of malignant schwannoma included the arrangement of the spindled tumor cells in a whorled pattern about thin-walled, gaping blood vessels, perivascular cellular proliferation and the presence of prominent myxoid stroma containing abundant hyaluronidase-sensitive acid mucopolysaccharides. Nuclear palisading was present in only one case. Eight tumors containing both neoplastic Schwann cells and rhabdomyoblasts and five containing both neoplastic Schwann cells and rhabdomyoblasts (malignant \"Triton\" tumors) and five containing foci of malignant cartilage cells were included in the series. The neoplasms occurred principally in adults (median age, 34 years) and were most common in the lower extremity (18 cases) and retroperitoneum (11 cases). A mass with or without pain was the most common presenting symptom (28 cases). The median size of excised tumors was 11 cm. The malignant schwannomas were highly malignant neoplasms, causing the death of 39 patients within five years and two patients within 6--10 years after diagnosis. Only four patients were alive and free of tumor 5--15 years after diagnosis.", "contents": "Malignant Schwannoma associated with von Recklinghausen's neurofibromatosis. A series of 46 malignant schwannomas occurring in soft parts of patients having von Recklinghausen's neurofibromatosis was analyzed. The diagnosis of malignant schwannoma was based upon the occurrence of malignant spindled cells closely resembling Schwann cells in the neoplasm and the close association or origin of the malignant schwannoma in a neurofibroma (27 tumors), or a large peripheral nerve (31 tumors). Additional histologic features useful in making the diagnosis of malignant schwannoma included the arrangement of the spindled tumor cells in a whorled pattern about thin-walled, gaping blood vessels, perivascular cellular proliferation and the presence of prominent myxoid stroma containing abundant hyaluronidase-sensitive acid mucopolysaccharides. Nuclear palisading was present in only one case. Eight tumors containing both neoplastic Schwann cells and rhabdomyoblasts and five containing both neoplastic Schwann cells and rhabdomyoblasts (malignant \"Triton\" tumors) and five containing foci of malignant cartilage cells were included in the series. The neoplasms occurred principally in adults (median age, 34 years) and were most common in the lower extremity (18 cases) and retroperitoneum (11 cases). A mass with or without pain was the most common presenting symptom (28 cases). The median size of excised tumors was 11 cm. The malignant schwannomas were highly malignant neoplasms, causing the death of 39 patients within five years and two patients within 6--10 years after diagnosis. Only four patients were alive and free of tumor 5--15 years after diagnosis."} {"id": "PMID:157613", "title": "[Rule of homology and morbid anatomy (author's transl)].", "content": "1. According to J.W. Goethe, morphology is a theory of evolution, H. Braus defined it as a theory of historic incidents, and according to D. Starck morphology is the role of shapes of the organisms. 2. The term homology was coined by morphologic researchers. Of course, it is used nowadays also in mathematics, chemistry, and linguistics and other logic matters. 3. Homologies have a special position in Goethe's work on the theory of types. Goethe's morphologic research and Schiller's aesthetic speculations are considered to be the origin of a 'typologic point of view.' 4. Coherences of Platon's theory of ideas and Goethe's theory of types are scrutinized. The theory of shapes ('Gestalt theory') is inconceivable without Platon's theory, and scientic morphology is inconceivable without shapes, either, and according to C. v. Ehrenfels \"Gestaltphilosophie\" could not exist without the shapes of Platon's theory. 5. It is shown that without Gestalt philosophy one cannot comprehend the following coherences: Gestalt (shape) as an idea, idea as a type of Goethe's rule, type as an element of the theory of homologies and even of constitution. 6. Homology will be constituted using certain criterions: a) detection of an equal descent, b) equal position of organismic structures in individuals, c) evidence of interpositions, and d) certain qualities of parts which are compared with each other. Homologous structures may be dissimilar in their architecture. 7. The term homology is explained a) by giving an analysis of morphologic and teratologic lines, b) by scrutinizing froms of symmetry, and c) by presenting the histopathology of topographical diverse but according to the morphogenetic mode coinciding tumours which are resembling each other in their microscopic patterns. 8. The application of the rule of homology in the morphologic investigation of diseases proves to be a) valuable from a heuristic point of view, b) an instrument of communication to characterize comparable matters, c) a means of classification, and d) a basic requirement to uncover inconceivable correlations of morphologic patterns in the first instance and then a basis for the prognosis findings which may be expected in the future. So far the didactic value of proven homologies is inestimably great. 9. The application of the rules of homology in morbild anatomy requires controls by 'regulatives.' There are: a) all facts must be born in mind, b) the rules of the mathematical logic, those of demonstrative and plausible conclusions need to be taken into consideration, and c) the criterions of Ehrenfels should be applied accurately. 10. At the contact surface of two scientific fields special difficulties may emerge. As far as contemporary pathology is concerned, elements of the Arts should be assimilated. This challenge is by no means a novel one. Covered traces of it could be found in our archive 50 years ago. We should not forget but keep in mind these elements.", "contents": "[Rule of homology and morbid anatomy (author's transl)]. 1. According to J.W. Goethe, morphology is a theory of evolution, H. Braus defined it as a theory of historic incidents, and according to D. Starck morphology is the role of shapes of the organisms. 2. The term homology was coined by morphologic researchers. Of course, it is used nowadays also in mathematics, chemistry, and linguistics and other logic matters. 3. Homologies have a special position in Goethe's work on the theory of types. Goethe's morphologic research and Schiller's aesthetic speculations are considered to be the origin of a 'typologic point of view.' 4. Coherences of Platon's theory of ideas and Goethe's theory of types are scrutinized. The theory of shapes ('Gestalt theory') is inconceivable without Platon's theory, and scientic morphology is inconceivable without shapes, either, and according to C. v. Ehrenfels \"Gestaltphilosophie\" could not exist without the shapes of Platon's theory. 5. It is shown that without Gestalt philosophy one cannot comprehend the following coherences: Gestalt (shape) as an idea, idea as a type of Goethe's rule, type as an element of the theory of homologies and even of constitution. 6. Homology will be constituted using certain criterions: a) detection of an equal descent, b) equal position of organismic structures in individuals, c) evidence of interpositions, and d) certain qualities of parts which are compared with each other. Homologous structures may be dissimilar in their architecture. 7. The term homology is explained a) by giving an analysis of morphologic and teratologic lines, b) by scrutinizing froms of symmetry, and c) by presenting the histopathology of topographical diverse but according to the morphogenetic mode coinciding tumours which are resembling each other in their microscopic patterns. 8. The application of the rule of homology in the morphologic investigation of diseases proves to be a) valuable from a heuristic point of view, b) an instrument of communication to characterize comparable matters, c) a means of classification, and d) a basic requirement to uncover inconceivable correlations of morphologic patterns in the first instance and then a basis for the prognosis findings which may be expected in the future. So far the didactic value of proven homologies is inestimably great. 9. The application of the rules of homology in morbild anatomy requires controls by 'regulatives.' There are: a) all facts must be born in mind, b) the rules of the mathematical logic, those of demonstrative and plausible conclusions need to be taken into consideration, and c) the criterions of Ehrenfels should be applied accurately. 10. At the contact surface of two scientific fields special difficulties may emerge. As far as contemporary pathology is concerned, elements of the Arts should be assimilated. This challenge is by no means a novel one. Covered traces of it could be found in our archive 50 years ago. We should not forget but keep in mind these elements."} {"id": "PMID:157614", "title": "Seminoma with syncytiotrophoblastic giant cells. A special form of seminoma.", "content": "Testicular seminomas may occur in various forms, of which the classical and spermatocytic are distinct, the anaplastic or atypical seminomas, however, less clearly defined. Lately, a separate group of particular clinical significance, comprising seminomas with syncytiotrophoblastic giant cells (STGC), has been specified. Although this type of seminoma had been recognized morphologically long ago, recent investigations have shown its ability to secret HCG, a fact that raises serious difficulties in its differential diagnosis with combined seminomas and choriocarcinomas. Two cases of seminomas with STGC are presented and pertinent clinical and morphologic problems discussed.", "contents": "Seminoma with syncytiotrophoblastic giant cells. A special form of seminoma. Testicular seminomas may occur in various forms, of which the classical and spermatocytic are distinct, the anaplastic or atypical seminomas, however, less clearly defined. Lately, a separate group of particular clinical significance, comprising seminomas with syncytiotrophoblastic giant cells (STGC), has been specified. Although this type of seminoma had been recognized morphologically long ago, recent investigations have shown its ability to secret HCG, a fact that raises serious difficulties in its differential diagnosis with combined seminomas and choriocarcinomas. Two cases of seminomas with STGC are presented and pertinent clinical and morphologic problems discussed."} {"id": "PMID:157620", "title": "Ultrastructural studies on the evolution of amyloidosis in the cyclic hematopoietic (CH) dog.", "content": "Electron microscopy studies were made on tissues of cyclic hematopoietic (CH) dogs of various ages presenting a high incidence of spontaneous amyloidosis. The distribution and morphologic characteristics of amyloidosis in this animal model closely correspond to the secondary and familial forms of the disease in humans. Plasma cells and, particularly, macrophages presented marked changes during the evolution of amyloid deposition. Residual bodies in the macrophages contained abundant cell debris, a result of both endocytic and autophagocytic activities. Intracellular amyloid fibrils were not observed by conventional electron microscopy. A few reticular cells contained intracytoplasmic fibrils which were morphologically different from amyloid. There was no correlation between the amount of intracellular fibrils and the size of the extracellular amyloid deposits. On the contrary, a temporal association between the magnitude of the amyloid deposits and cytoplasmic changes in the macrophages at sequential stages of the evolution of the disease was evident. It is suggested that the hematopoietic defect in the CH dog could play an important role in the production of amyloidosis, making this animal an excellent experimental model for studies of that disease.", "contents": "Ultrastructural studies on the evolution of amyloidosis in the cyclic hematopoietic (CH) dog. Electron microscopy studies were made on tissues of cyclic hematopoietic (CH) dogs of various ages presenting a high incidence of spontaneous amyloidosis. The distribution and morphologic characteristics of amyloidosis in this animal model closely correspond to the secondary and familial forms of the disease in humans. Plasma cells and, particularly, macrophages presented marked changes during the evolution of amyloid deposition. Residual bodies in the macrophages contained abundant cell debris, a result of both endocytic and autophagocytic activities. Intracellular amyloid fibrils were not observed by conventional electron microscopy. A few reticular cells contained intracytoplasmic fibrils which were morphologically different from amyloid. There was no correlation between the amount of intracellular fibrils and the size of the extracellular amyloid deposits. On the contrary, a temporal association between the magnitude of the amyloid deposits and cytoplasmic changes in the macrophages at sequential stages of the evolution of the disease was evident. It is suggested that the hematopoietic defect in the CH dog could play an important role in the production of amyloidosis, making this animal an excellent experimental model for studies of that disease."} {"id": "PMID:157622", "title": "[\"Malabsorptive\" dermatitis herpetiformis. A study with particular regard to biopsy findings of the small intestine (author's transl)].", "content": "21 patients (6 females and 15 males) with Dermatitis herpetiformis have been studied with special considerations of the small intestinal biopsy-findings. During this investigation the patient's mean age was 45 years (20-68) and the mean age at onset was 38 years (17-64). In 5 patients (23.8%) total villous atrophy (group I) and in 4 patients (19.0%) a severe partial or subtotal villous trophy (group II) was found on small intestinal biopsy. The sprue-like changes were patchy lesions. Histocompatibility-antigens of type HLA-AL were found in 38.1% and of type HLA-B8 in 47.6%. After 20 years of the disease one patient died of a malignant lymphoma of the intestine (immunoblastic sarcoma). In all patients the number of interepithelial lymphocytes in the small bowel mucose was significantly increased, as it was in those patients with a normal villous pattern (group III). In a quantitative analysis of specifically labeled (peroxidase-anti-perosidase complex) IgG-, IgA- and IgM-cells in the intestinal mucosa it was found that the number of all three plasma cell classes are increased significantly (P less than 0.01).", "contents": "[\"Malabsorptive\" dermatitis herpetiformis. A study with particular regard to biopsy findings of the small intestine (author's transl)]. 21 patients (6 females and 15 males) with Dermatitis herpetiformis have been studied with special considerations of the small intestinal biopsy-findings. During this investigation the patient's mean age was 45 years (20-68) and the mean age at onset was 38 years (17-64). In 5 patients (23.8%) total villous atrophy (group I) and in 4 patients (19.0%) a severe partial or subtotal villous trophy (group II) was found on small intestinal biopsy. The sprue-like changes were patchy lesions. Histocompatibility-antigens of type HLA-AL were found in 38.1% and of type HLA-B8 in 47.6%. After 20 years of the disease one patient died of a malignant lymphoma of the intestine (immunoblastic sarcoma). In all patients the number of interepithelial lymphocytes in the small bowel mucose was significantly increased, as it was in those patients with a normal villous pattern (group III). In a quantitative analysis of specifically labeled (peroxidase-anti-perosidase complex) IgG-, IgA- and IgM-cells in the intestinal mucosa it was found that the number of all three plasma cell classes are increased significantly (P less than 0.01)."} {"id": "PMID:157623", "title": "Leiomyosarcoma of the pulmonary artery. A light and electronmicroscopical study.", "content": "A 25-year-old man with chest pain and shortness of breath was found to have a primary sarcoma of the pumonary artery. On light- and electronmicroscopy and immunofluorescence microscopy the lesion was found to be composed of cells of smooth muscle origin. It was diagnosed as leiomyosarcoma. The cross and microscopic features of the tumor are described and the morphologic characteristics of previously reported vascular sarcomas are briefly reviewed.", "contents": "Leiomyosarcoma of the pulmonary artery. A light and electronmicroscopical study. A 25-year-old man with chest pain and shortness of breath was found to have a primary sarcoma of the pumonary artery. On light- and electronmicroscopy and immunofluorescence microscopy the lesion was found to be composed of cells of smooth muscle origin. It was diagnosed as leiomyosarcoma. The cross and microscopic features of the tumor are described and the morphologic characteristics of previously reported vascular sarcomas are briefly reviewed."} {"id": "PMID:157624", "title": "Cavernous hemangioma of optic chiasm, optic nerves and right optic tract. Case report and review of literature.", "content": "Diminishing right ocular visual acuity for three weeks in a 30 year old man was confirmed by examination. Bilateral scotomata and bitemporal hemiachromatopsia indicated a chiasmal lesion; reduced visual acuity and Marcus Gunn pupil of the right eye and left relative temporal hemianopia indicated asymmetric involvement. Erythrocytes in the CSF verified a suspected subarachnoid bleed; contrast-enhanced CAT scan demonstrated a suprasellar mass. A cystic, multiloculated, bluish mass distorted the right optic nerve, tract, and chiasm. A hematoma was evacuated and biopsy revealed a cavernous hemangioma of the right optic nerve. Post-operatively, visual acuity has recovered in the right eye but a left homonymous temporal hemianopia has developed.", "contents": "Cavernous hemangioma of optic chiasm, optic nerves and right optic tract. Case report and review of literature. Diminishing right ocular visual acuity for three weeks in a 30 year old man was confirmed by examination. Bilateral scotomata and bitemporal hemiachromatopsia indicated a chiasmal lesion; reduced visual acuity and Marcus Gunn pupil of the right eye and left relative temporal hemianopia indicated asymmetric involvement. Erythrocytes in the CSF verified a suspected subarachnoid bleed; contrast-enhanced CAT scan demonstrated a suprasellar mass. A cystic, multiloculated, bluish mass distorted the right optic nerve, tract, and chiasm. A hematoma was evacuated and biopsy revealed a cavernous hemangioma of the right optic nerve. Post-operatively, visual acuity has recovered in the right eye but a left homonymous temporal hemianopia has developed."} {"id": "PMID:157625", "title": "Peliosis hepatis as a result of endogenous steroid hormone production.", "content": "A case of peliosis hepatis in a 3 year old child with steroid hormone producing adreanl tumour is presented. The diagnosis of the adrenal tumour and peliosis hepatis was settled on the basis of surgical material examination. This case of peliosis hepatis due to endogenous steroid production lends more support to the earlier reported cases of iatrogenically produced peliosis due to exogenous steroid treatment.", "contents": "Peliosis hepatis as a result of endogenous steroid hormone production. A case of peliosis hepatis in a 3 year old child with steroid hormone producing adreanl tumour is presented. The diagnosis of the adrenal tumour and peliosis hepatis was settled on the basis of surgical material examination. This case of peliosis hepatis due to endogenous steroid production lends more support to the earlier reported cases of iatrogenically produced peliosis due to exogenous steroid treatment."} {"id": "PMID:157628", "title": "[Mucopolysaccharides, collagen and calcium of bone regenerate in replacing a bone defect by a method of unilocular compression-distraction osteosynthesis].", "content": "Intensive synthesis of collagen, which constitutes the basis of organic matrix in bone tissue, was observed in the regenerate developed during compression-distractional osteoxynthesis. The organic matrix of the regenerate was quickly mineralized; after termination of the distraction it contained more than a half of calcium as compared with the mature bone of healthy animals. Relatively low accumulation of mucopolysaccharides in the regenerate appears to depend on development of favourable conditions of its blood supply together with suitable fixation of bone fragments.", "contents": "[Mucopolysaccharides, collagen and calcium of bone regenerate in replacing a bone defect by a method of unilocular compression-distraction osteosynthesis]. Intensive synthesis of collagen, which constitutes the basis of organic matrix in bone tissue, was observed in the regenerate developed during compression-distractional osteoxynthesis. The organic matrix of the regenerate was quickly mineralized; after termination of the distraction it contained more than a half of calcium as compared with the mature bone of healthy animals. Relatively low accumulation of mucopolysaccharides in the regenerate appears to depend on development of favourable conditions of its blood supply together with suitable fixation of bone fragments."} {"id": "PMID:157639", "title": "Testosterone metabolism in normal males and male cirrhotics.", "content": "The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis.", "contents": "Testosterone metabolism in normal males and male cirrhotics. The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis."} {"id": "PMID:157643", "title": "[Echocardiographic studies on athletes of various sport-types and non-athletic persons (author's transl)].", "content": "The results of echocardiographic studies on 90 athletes representing various sport-types and 18 non-athletic persons are presented. The intracardiac diameter measured by echocardiography was proportional to the heart volume determined radiologically. The thickness of the septum and posterior heart wall compared to the internal heart diameter was greater in athletes with static exercise than in endurance athletes. This must be interpreted as a tendency to concentric hypertrophy. In endurance athletes this relationship tended to be less than in non-athletic persons. In addition stroke volume and cardiac output at rest was higher in endurance athletes than in athletes with static exercise and non-athletic persons. At rest no variations in parameters of heart muscle contractility related to heart size or sport-type could be detected.", "contents": "[Echocardiographic studies on athletes of various sport-types and non-athletic persons (author's transl)]. The results of echocardiographic studies on 90 athletes representing various sport-types and 18 non-athletic persons are presented. The intracardiac diameter measured by echocardiography was proportional to the heart volume determined radiologically. The thickness of the septum and posterior heart wall compared to the internal heart diameter was greater in athletes with static exercise than in endurance athletes. This must be interpreted as a tendency to concentric hypertrophy. In endurance athletes this relationship tended to be less than in non-athletic persons. In addition stroke volume and cardiac output at rest was higher in endurance athletes than in athletes with static exercise and non-athletic persons. At rest no variations in parameters of heart muscle contractility related to heart size or sport-type could be detected."} {"id": "PMID:157644", "title": "[Ventricular and myocardial function in mitral regurgitation (author's transl)].", "content": "Left ventricular and myocardial performance were analyzed in 9 patients with chronic volume overload by mitral regurgitation from biplane cineventriculograms, simultaneous pressure recordings and cardiac output (thermodilution method) determinations. In spite of a considerable regurgitant fraction (49 +/- 17% of total stroke volume) cardiac index on the average is normal (CI = 3.3 +/- 0.7 l . min-1). The main compensatory mechanism to maintain cardiac ouput in hypertorphy (WED = 1.1 +/- 0.2 cm; LVMI = 216 +/- 62 g . m-2; LVMI/EDVI = 1.3 +/- 0.3 g . ml-1) and dilatation (EDVI = 163 +/- 37 ml . m-2). An increase of preload is of minor importance (PLVED = 15 +/- 7 mmHg; sigma ED = (40 +/- 19) x 10(3) dyn . cm-2). Left ventricular enlargement and wall mass are related to the degree of clinical heart failure (NYHA). Enddiastolic volume on the average is more increased than total stroke volume (89 +/- 31 ml . m-2). Ejection fraction (EF = 54 +/- 7%) was depressed despite a normal afterload (sigma tej = (171 +/- 37 x 10(3) dyn. cm-2; sigma max = (247 +/- 48 x 10(3) dyn . cm-2). The reduced ejection fraction and diminished myocardial power are related to an impairment of myocardial function (VMW . sigma tej = (83 +/- 39) x 10(3) dyn . cm-2 . s-1; VMW . sigma tej/ln sigma ED = 7.9 +/- 3.6 x 10(3) dyn . cm-2 . s-1). In comparable degrees of heart failure myocardial function is more compromised in patients with mitral than with aortic regurgitation.", "contents": "[Ventricular and myocardial function in mitral regurgitation (author's transl)]. Left ventricular and myocardial performance were analyzed in 9 patients with chronic volume overload by mitral regurgitation from biplane cineventriculograms, simultaneous pressure recordings and cardiac output (thermodilution method) determinations. In spite of a considerable regurgitant fraction (49 +/- 17% of total stroke volume) cardiac index on the average is normal (CI = 3.3 +/- 0.7 l . min-1). The main compensatory mechanism to maintain cardiac ouput in hypertorphy (WED = 1.1 +/- 0.2 cm; LVMI = 216 +/- 62 g . m-2; LVMI/EDVI = 1.3 +/- 0.3 g . ml-1) and dilatation (EDVI = 163 +/- 37 ml . m-2). An increase of preload is of minor importance (PLVED = 15 +/- 7 mmHg; sigma ED = (40 +/- 19) x 10(3) dyn . cm-2). Left ventricular enlargement and wall mass are related to the degree of clinical heart failure (NYHA). Enddiastolic volume on the average is more increased than total stroke volume (89 +/- 31 ml . m-2). Ejection fraction (EF = 54 +/- 7%) was depressed despite a normal afterload (sigma tej = (171 +/- 37 x 10(3) dyn. cm-2; sigma max = (247 +/- 48 x 10(3) dyn . cm-2). The reduced ejection fraction and diminished myocardial power are related to an impairment of myocardial function (VMW . sigma tej = (83 +/- 39) x 10(3) dyn . cm-2 . s-1; VMW . sigma tej/ln sigma ED = 7.9 +/- 3.6 x 10(3) dyn . cm-2 . s-1). In comparable degrees of heart failure myocardial function is more compromised in patients with mitral than with aortic regurgitation."} {"id": "PMID:157645", "title": "Comparative cytomorphology of the avian adrenocortical tissue.", "content": "The histology and histochemistry of the interrenal gland of twenty avian species have been described in this report. The avian interrenal tissue, on the basis of nuclear orientation and other cytomorphic features, can be classified into six cytologically distinct types. Cytomorphic organization within the interrenal tissue of these avian species also indicates some regional demarcation into subcapsular and central zones. Zonal demarcation in the interrenal tissue of these birds has also been indicated from chemocytological investigation. Paradoxically not much of correspondence was noticed in the cytologic and cytochemical patterns. The cytological and cytochemical studies fail to indicate any phylogenetic trend within the interrenal tissue of the birds under investigation.", "contents": "Comparative cytomorphology of the avian adrenocortical tissue. The histology and histochemistry of the interrenal gland of twenty avian species have been described in this report. The avian interrenal tissue, on the basis of nuclear orientation and other cytomorphic features, can be classified into six cytologically distinct types. Cytomorphic organization within the interrenal tissue of these avian species also indicates some regional demarcation into subcapsular and central zones. Zonal demarcation in the interrenal tissue of these birds has also been indicated from chemocytological investigation. Paradoxically not much of correspondence was noticed in the cytologic and cytochemical patterns. The cytological and cytochemical studies fail to indicate any phylogenetic trend within the interrenal tissue of the birds under investigation."} {"id": "PMID:157646", "title": "Physiological adaptation in relation to hyperosmotic stress in the epidermis of a fresh-water teleost Barbus sophor (Cypriniformes, Cyprinidae): a histochemical study.", "content": "The changes in distribution of mucopolysaccharides, glycogen and protein bound sulphydryl groups of cysteine in the various cellular components of the epidermis of Barbus sophor along with its structural alterations as a result of hyperosmotic stress, have been described using histochemical techniques. The hyperosmotic saline induces a cyclic secretion of acid mucopolysaccharides by the mucous cells. Simultaneously the polygonal cells also show a marked disturbance in the processes of mucogenesis and keratinization, indicating an inverse relationship between the degree of keratinization and the amount of mucus secreted by epidermis. The role of glycogen in the polygonal cells has been discussed in relation to disturbed mucogenesis. The appearance of intercellular spaces in basal layer and middle layer has been correlated with the passage for movement of increased amounts of nutrients through the skin.", "contents": "Physiological adaptation in relation to hyperosmotic stress in the epidermis of a fresh-water teleost Barbus sophor (Cypriniformes, Cyprinidae): a histochemical study. The changes in distribution of mucopolysaccharides, glycogen and protein bound sulphydryl groups of cysteine in the various cellular components of the epidermis of Barbus sophor along with its structural alterations as a result of hyperosmotic stress, have been described using histochemical techniques. The hyperosmotic saline induces a cyclic secretion of acid mucopolysaccharides by the mucous cells. Simultaneously the polygonal cells also show a marked disturbance in the processes of mucogenesis and keratinization, indicating an inverse relationship between the degree of keratinization and the amount of mucus secreted by epidermis. The role of glycogen in the polygonal cells has been discussed in relation to disturbed mucogenesis. The appearance of intercellular spaces in basal layer and middle layer has been correlated with the passage for movement of increased amounts of nutrients through the skin."} {"id": "PMID:157649", "title": "[Primary visual cortex response recovery cycles caused by pharmacologic and electrical effects on the monoaminergic systems of the rat brain].", "content": "The recovery cycles (RC) of primary responses in the visual cortex were studied in alert rats following the electrical stimulation of raphe nuclei and locus coeruleus as well as following pharmacological and complex (electrical and pharmacological) actions on serotonin- and noradrenergic brain systems. It was found that both electrical and pharmacological actions on the above monoaminergic systems reduce the duration and depth of relative non-reactivity phase of RC. Complex (electrical and pharmacological) action leads to heterodirectional changes in RC. The character of these changes reflects the reciprocity existing in functional interrelations between serotonin- and noradrenergic brain systems. The probable connection of the found effects with memory mechanisms is discussed.", "contents": "[Primary visual cortex response recovery cycles caused by pharmacologic and electrical effects on the monoaminergic systems of the rat brain]. The recovery cycles (RC) of primary responses in the visual cortex were studied in alert rats following the electrical stimulation of raphe nuclei and locus coeruleus as well as following pharmacological and complex (electrical and pharmacological) actions on serotonin- and noradrenergic brain systems. It was found that both electrical and pharmacological actions on the above monoaminergic systems reduce the duration and depth of relative non-reactivity phase of RC. Complex (electrical and pharmacological) action leads to heterodirectional changes in RC. The character of these changes reflects the reciprocity existing in functional interrelations between serotonin- and noradrenergic brain systems. The probable connection of the found effects with memory mechanisms is discussed."} {"id": "PMID:157661", "title": "[Human IgG subclass study. II. The levels of the individual IgG subclasses in paired sera from mothers and newborn infants as well as in the blood sera of inhabitants of an isolated northern village].", "content": "The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect.", "contents": "[Human IgG subclass study. II. The levels of the individual IgG subclasses in paired sera from mothers and newborn infants as well as in the blood sera of inhabitants of an isolated northern village]. The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect."} {"id": "PMID:157663", "title": "Effect of some heterocyclic compounds on human semen composition and biology.", "content": "The effect of some heterocyclic compounds on some aspects of human semen metabolism was studied. Caffeine produced stimulation of motility and lactic acid production and an inhibition of fructose utilization and oxygen uptake. Nicotinamide and riboflavin produced stimulation of motility, fructose utilization and oxygen uptake and an inhibition of lactic acid production.", "contents": "Effect of some heterocyclic compounds on human semen composition and biology. The effect of some heterocyclic compounds on some aspects of human semen metabolism was studied. Caffeine produced stimulation of motility and lactic acid production and an inhibition of fructose utilization and oxygen uptake. Nicotinamide and riboflavin produced stimulation of motility, fructose utilization and oxygen uptake and an inhibition of lactic acid production."} {"id": "PMID:157664", "title": "[Histotopochemical and electronmicroscopical investigations of Wistar-rats with streptozotocin diabetes (author's transl)].", "content": "15 streptozotocin-diabetic wistar rats (an application of a single dose of 64 mg/kg body weight streptozotocin) and a control group of 12 wistar rats with a healthy metabolism have been examined. The majority of B-cells was largely degranulated, insulin was hardly or not to be found with histochemical methods. The A- and B-cells of 11 test animals showed pathological findings: Karyolysis, the dissolution of cell membranes and the decay of cytoplasm which are criteria of necrosis. Besides a round-cell infiltration could be found as a symptom of insulitis. The B-cells showed only single granula under the electron microscope. The endoplasmatic reticulum was only poorly developed and with hardly any ribosomes. There were only very little mitochondria and no GOLGI's apparatus. The cell membrane was smooth and not enlarged by microvilli. Emiocytosis-figures were missing. No changes of nuclei could be noticed. The findings on organelles correlate well with the microscopical results. The exocrine parenchyma contained regions showing the decay of the lobule structure as well as of single acini. The acinus cells were in necrosis. The connective tissue was obviously increased. There were regions in the stroma with a round-cell infiltration as found with a pancreatitis. Both these and the results discussed from our literature show that streptozotocin does not only affect the B-cells of the islets of LANGERHANS, but also the exocrine pancreas and other organs.", "contents": "[Histotopochemical and electronmicroscopical investigations of Wistar-rats with streptozotocin diabetes (author's transl)]. 15 streptozotocin-diabetic wistar rats (an application of a single dose of 64 mg/kg body weight streptozotocin) and a control group of 12 wistar rats with a healthy metabolism have been examined. The majority of B-cells was largely degranulated, insulin was hardly or not to be found with histochemical methods. The A- and B-cells of 11 test animals showed pathological findings: Karyolysis, the dissolution of cell membranes and the decay of cytoplasm which are criteria of necrosis. Besides a round-cell infiltration could be found as a symptom of insulitis. The B-cells showed only single granula under the electron microscope. The endoplasmatic reticulum was only poorly developed and with hardly any ribosomes. There were only very little mitochondria and no GOLGI's apparatus. The cell membrane was smooth and not enlarged by microvilli. Emiocytosis-figures were missing. No changes of nuclei could be noticed. The findings on organelles correlate well with the microscopical results. The exocrine parenchyma contained regions showing the decay of the lobule structure as well as of single acini. The acinus cells were in necrosis. The connective tissue was obviously increased. There were regions in the stroma with a round-cell infiltration as found with a pancreatitis. Both these and the results discussed from our literature show that streptozotocin does not only affect the B-cells of the islets of LANGERHANS, but also the exocrine pancreas and other organs."} {"id": "PMID:157665", "title": "Studies on the superprecipitation of actomyosin in isoproterenol-induced cardiac hypertrophy.", "content": "Superprecipitation of normal and hypertrophic cardiac actomyosin--made from individually purified cardiac myosin and skeletal F-actin-, compared with that of synthetic skeletal actomyosin was investigated. A proportional relationship was found between the extent maximum of superprecipitation (Emax) and the concentration of actomyosin complex in the range of 0.1-0.5 mg protein/ml. At 3 X 10(-5) M ATP the Emax was higher in the case of skeletal actomyosin than ardiac actomyosin. At 1.5 X 10(-4) M ATP the superprecipitation was preceded by clearing phase and the time required for the half-maximal increase of turbidity (t//2) was longer for cardiac actomyosin than skeletal actomyosin. The superprecipitation was promoted by decreasing Mg2+ concentration, while the increase in Mg2+ concentration inhibited the superprecipitation and caused the prolongation of clearing phase. The decreased superprecipitation of the actomyosin from hypertrophied hearts and the narrower potassium chloride concentration range, in which the superprecipitation took place, may be the consequence of the significantly lower ATPase activity.", "contents": "Studies on the superprecipitation of actomyosin in isoproterenol-induced cardiac hypertrophy. Superprecipitation of normal and hypertrophic cardiac actomyosin--made from individually purified cardiac myosin and skeletal F-actin-, compared with that of synthetic skeletal actomyosin was investigated. A proportional relationship was found between the extent maximum of superprecipitation (Emax) and the concentration of actomyosin complex in the range of 0.1-0.5 mg protein/ml. At 3 X 10(-5) M ATP the Emax was higher in the case of skeletal actomyosin than ardiac actomyosin. At 1.5 X 10(-4) M ATP the superprecipitation was preceded by clearing phase and the time required for the half-maximal increase of turbidity (t//2) was longer for cardiac actomyosin than skeletal actomyosin. The superprecipitation was promoted by decreasing Mg2+ concentration, while the increase in Mg2+ concentration inhibited the superprecipitation and caused the prolongation of clearing phase. The decreased superprecipitation of the actomyosin from hypertrophied hearts and the narrower potassium chloride concentration range, in which the superprecipitation took place, may be the consequence of the significantly lower ATPase activity."} {"id": "PMID:157660", "title": "[Plasma androgen levels in Papio hamadryas pavian hamadrils at different periods of postnatal development].", "content": "Using radioimmunological assay, it has been demonstrated that at the age of 0.5, 1 and 2 years sexual differences are absent in the concentration of testosteron, 5 alpha-dihydrotestosteron, dehydroepiandrosteron and delta 4-androstendion in the blood plasma. The level of testosteron in sexually immature animals does not differ from that in adult females. In sexually mature baboons, testosteron content was found to be more than 20 times higher. The activity of 5 alpha-reductase, checked by the ratio of concentrations of testosteron and 5 alpha-dihydrotestosteron, in adult males was 4 times lower than in sexually immature animals. No significant changes in delta 4-androstendion concentration were noted during the development of androgenic function. Dehydroepiandrosteron content of the peripheral blood in immature baboons is several times higher than that in adult animals, which may be associated with postnatal activity of embryonic zone.", "contents": "[Plasma androgen levels in Papio hamadryas pavian hamadrils at different periods of postnatal development]. Using radioimmunological assay, it has been demonstrated that at the age of 0.5, 1 and 2 years sexual differences are absent in the concentration of testosteron, 5 alpha-dihydrotestosteron, dehydroepiandrosteron and delta 4-androstendion in the blood plasma. The level of testosteron in sexually immature animals does not differ from that in adult females. In sexually mature baboons, testosteron content was found to be more than 20 times higher. The activity of 5 alpha-reductase, checked by the ratio of concentrations of testosteron and 5 alpha-dihydrotestosteron, in adult males was 4 times lower than in sexually immature animals. No significant changes in delta 4-androstendion concentration were noted during the development of androgenic function. Dehydroepiandrosteron content of the peripheral blood in immature baboons is several times higher than that in adult animals, which may be associated with postnatal activity of embryonic zone."} {"id": "PMID:157666", "title": "Contraction properties and functional morphology of the avian stapedius muscle.", "content": "The influence of the stapedius muscle contraction on middle ear volume and acoustic impedance was investigated in the chicken, Gallus gallus. The time course of twitch responses to electrical stimulation (measured as volume and impedance changes) was found to be largely independent of the stimulus voltage, having a contraction time of 22 ms and a half-relaxation time of 22 ms. The stapedius muscle was therefore characterized as a fast twitch muscle. Slow contraction properties were also revealed: A summation of responses to repetitive stimulation beginning at 2.5 Hz and a slow decline to baseline were seen in volume and impedance change recordings. The morphological characteristics were consonant with that of a homogeneously fast muscle: Only fibres with high ATPase activity were identified and no fibres with \"en grappe\" or multiple innervation were observed. The slow characteristics were suggested to be due to visco-elastic elements in the middle ear. The chicken stapedius muscle is suggested to be analogous to both the stapedius and the tensor tympani of mammals.", "contents": "Contraction properties and functional morphology of the avian stapedius muscle. The influence of the stapedius muscle contraction on middle ear volume and acoustic impedance was investigated in the chicken, Gallus gallus. The time course of twitch responses to electrical stimulation (measured as volume and impedance changes) was found to be largely independent of the stimulus voltage, having a contraction time of 22 ms and a half-relaxation time of 22 ms. The stapedius muscle was therefore characterized as a fast twitch muscle. Slow contraction properties were also revealed: A summation of responses to repetitive stimulation beginning at 2.5 Hz and a slow decline to baseline were seen in volume and impedance change recordings. The morphological characteristics were consonant with that of a homogeneously fast muscle: Only fibres with high ATPase activity were identified and no fibres with \"en grappe\" or multiple innervation were observed. The slow characteristics were suggested to be due to visco-elastic elements in the middle ear. The chicken stapedius muscle is suggested to be analogous to both the stapedius and the tensor tympani of mammals."} {"id": "PMID:157667", "title": "Transverse diameter of chest and heart after birth asphyxia in the newborn infant.", "content": "The transverse diameter of the chest and heart was measured in 745 newborn infants after birth asphyxia. Both diameters showed a good correlation with birth weight. The great individual variations of the measurements were due to different degrees of birth asphyxia observed in the infants and to their different responses to compensate asphyxia. A wet lung and an increased transverse diameter of the chest (above the 90th percentile) indicate a good, and a decreased transverse diameter of the chest (bellow the 10th percentile) indicate a bad prognosis for survival. The cardiomegaly usually disappears after the first 12 hours of life, but in some cases it persists for more than 5 days, depending on the severity of birth asphyxia.", "contents": "Transverse diameter of chest and heart after birth asphyxia in the newborn infant. The transverse diameter of the chest and heart was measured in 745 newborn infants after birth asphyxia. Both diameters showed a good correlation with birth weight. The great individual variations of the measurements were due to different degrees of birth asphyxia observed in the infants and to their different responses to compensate asphyxia. A wet lung and an increased transverse diameter of the chest (above the 90th percentile) indicate a good, and a decreased transverse diameter of the chest (bellow the 10th percentile) indicate a bad prognosis for survival. The cardiomegaly usually disappears after the first 12 hours of life, but in some cases it persists for more than 5 days, depending on the severity of birth asphyxia."} {"id": "PMID:157668", "title": "Partial purification and properties of bovine heart catalase.", "content": "Catalase was partially purified (about 380-fold purification) from the post-mitochondrial supernatant of bovine heart and compared with catalases from bovine erythrocytes and bovine liver. The electrophoretic mobility in polyacrylamide gel (pH 8.0) of heart catalase was the same as that of erythrocyte catalase and was smaller than that of the liver enzyme. The heart catalase was indistinguishable from erythrocyte catalase in regard to the molecular weights of subunit polypeptides, the inhibition patterns produced by several catalase inhibitors, and specific activity. The pH-activity curve of heart catalase consisted of a characteristic biphasic pattern with a peak at pH 7.5 and a shoulder at pH 10.", "contents": "Partial purification and properties of bovine heart catalase. Catalase was partially purified (about 380-fold purification) from the post-mitochondrial supernatant of bovine heart and compared with catalases from bovine erythrocytes and bovine liver. The electrophoretic mobility in polyacrylamide gel (pH 8.0) of heart catalase was the same as that of erythrocyte catalase and was smaller than that of the liver enzyme. The heart catalase was indistinguishable from erythrocyte catalase in regard to the molecular weights of subunit polypeptides, the inhibition patterns produced by several catalase inhibitors, and specific activity. The pH-activity curve of heart catalase consisted of a characteristic biphasic pattern with a peak at pH 7.5 and a shoulder at pH 10."} {"id": "PMID:157669", "title": "Fibroma of the urinary bladder: a light and ultrastructural study of a case with review of the literature in Japan.", "content": "A hard fibroma of the urinary bladder was found in an autopsy case of a 69 year-old female. The tumor, 10x9x6 cm, occurred in the superior wall of the bladder. Ultrastructurally, the principal cells of the tumor were myofibroblasts. Fibroblasts and fibrocytes were also present. Including our case, the number of reported cases of pure fibroma of the urinary bladder in Japan is 12. These are reviewed briefly.", "contents": "Fibroma of the urinary bladder: a light and ultrastructural study of a case with review of the literature in Japan. A hard fibroma of the urinary bladder was found in an autopsy case of a 69 year-old female. The tumor, 10x9x6 cm, occurred in the superior wall of the bladder. Ultrastructurally, the principal cells of the tumor were myofibroblasts. Fibroblasts and fibrocytes were also present. Including our case, the number of reported cases of pure fibroma of the urinary bladder in Japan is 12. These are reviewed briefly."} {"id": "PMID:157670", "title": "Existence of serum HBe antigen and expression of liver HB surface and core antigens in hepatitis type B patients.", "content": "A study of 52 liver biopsies (47 hepatitis type B and 5 asymptomatic carriers) was performed to clarify the roles of HBe antigen (HBeAg), HB surface antigen (HBsAg) and HB core antigen (HBcAg). In this study, the Gudat classification was modified so as to classify the patterns of HB antigens into six reaction types including: type O (negative for both liver HBsAg and liver HBcAg), type III-A (characterized by a spotty HBsAg pattern) and type III-B (characterized from a sub-lobular to lobular HBsAg localization pattern). This classification enabled accurate prediction of the prognosis of hepatitis. Patients with positive serum HBeAg had either minimal hepatitis with mild clinical features or chronic aggressive hepatitis with severe clinical features. Ten patients negative for both HBeAg and HBeAb were all positive for liver HBcAg. In all 3 patients on corticosteroid administrations liver tissue was markedly positive for HBcAg and serum was usually positive for HBeAb.", "contents": "Existence of serum HBe antigen and expression of liver HB surface and core antigens in hepatitis type B patients. A study of 52 liver biopsies (47 hepatitis type B and 5 asymptomatic carriers) was performed to clarify the roles of HBe antigen (HBeAg), HB surface antigen (HBsAg) and HB core antigen (HBcAg). In this study, the Gudat classification was modified so as to classify the patterns of HB antigens into six reaction types including: type O (negative for both liver HBsAg and liver HBcAg), type III-A (characterized by a spotty HBsAg pattern) and type III-B (characterized from a sub-lobular to lobular HBsAg localization pattern). This classification enabled accurate prediction of the prognosis of hepatitis. Patients with positive serum HBeAg had either minimal hepatitis with mild clinical features or chronic aggressive hepatitis with severe clinical features. Ten patients negative for both HBeAg and HBeAb were all positive for liver HBcAg. In all 3 patients on corticosteroid administrations liver tissue was markedly positive for HBcAg and serum was usually positive for HBeAb."} {"id": "PMID:157671", "title": "Co-existence of inhibitory and stimulatory factors modulating cell proliferation in rat liver cytoplasm.", "content": "Factors that inhibit and stimulate cell proliferation were found to coexist in rat liver supernatant. The inhibitory and stimulatory factors were separated by ethanol fractionation. Both factors were sensitive to heat- and trypsin-treatment. The activity of the inhibitor was diminished by partial hepatectomy. The inhibitor from normal livers inhibited DNA and RNA synthesis in the L-cell system, but the same fraction from regenerating livers caused little or no inhibition of nucleic acid synthesis. The stimulatory factor from regenerating livers had a stronger effect on cell proliferation than that of normal livers. Furthermore, the inhibitor from normal livers depressed DNA synthesis in vivo in regenerating livers.", "contents": "Co-existence of inhibitory and stimulatory factors modulating cell proliferation in rat liver cytoplasm. Factors that inhibit and stimulate cell proliferation were found to coexist in rat liver supernatant. The inhibitory and stimulatory factors were separated by ethanol fractionation. Both factors were sensitive to heat- and trypsin-treatment. The activity of the inhibitor was diminished by partial hepatectomy. The inhibitor from normal livers inhibited DNA and RNA synthesis in the L-cell system, but the same fraction from regenerating livers caused little or no inhibition of nucleic acid synthesis. The stimulatory factor from regenerating livers had a stronger effect on cell proliferation than that of normal livers. Furthermore, the inhibitor from normal livers depressed DNA synthesis in vivo in regenerating livers."} {"id": "PMID:157672", "title": "Effect of Litoralon on the development of goblet cells of the intestinal mucosa during metamorphosis of the frog.", "content": "Gamma-L-glutmyl-taurine (Litoralon), a recently detected hormone of parathyroid gland, accelerates maturation of the gut of frog larvae and, similarly as vitamin A, it stimulates the synthesis of polysaccharides.", "contents": "Effect of Litoralon on the development of goblet cells of the intestinal mucosa during metamorphosis of the frog. Gamma-L-glutmyl-taurine (Litoralon), a recently detected hormone of parathyroid gland, accelerates maturation of the gut of frog larvae and, similarly as vitamin A, it stimulates the synthesis of polysaccharides."} {"id": "PMID:157676", "title": "The Arthus reaction in rats, a possible test for anti-inflammatory and antiheumatic drugs.", "content": "The Arthus reaction is an immunologically induced inflammatory response characterized by immune complex deposition, complement fixation, polymorphonuclear leukocyte infiltration and tissue damage. Many of these same pathological tissue alterations are found in the lesions of rheumatoid arthritis (RA). The similarities between the reversed passive Arthus reaction (RPAR) and RA led us to investigate the usefulness of the RPAR in the search for new antirheumatic agents. The RPAR was elicited in the skin of rats using chicken ovalbumin and the IgG fraction of rabbit anti-ovalbumin. Paramethasone, hydrocortisone, indomethacin, pirprofen, sulfinpyrazone, thalidomide and theophylline all gave significant inhibition of the RPAR. Ibuprofen, naproxen, cyprohepatadine and cromolyn sodium were inactive, while phenylbutazone and ASA exhibited a dose-dependent effect. The data show that the Arthus reaction, which is the result of the complex interaction of many factors, can be affected either generally or selectively at different time intervals by various therapeutic agents. The RPAR in rats may prove useful in detecting new therapeutic agents for the treatment of RA.", "contents": "The Arthus reaction in rats, a possible test for anti-inflammatory and antiheumatic drugs. The Arthus reaction is an immunologically induced inflammatory response characterized by immune complex deposition, complement fixation, polymorphonuclear leukocyte infiltration and tissue damage. Many of these same pathological tissue alterations are found in the lesions of rheumatoid arthritis (RA). The similarities between the reversed passive Arthus reaction (RPAR) and RA led us to investigate the usefulness of the RPAR in the search for new antirheumatic agents. The RPAR was elicited in the skin of rats using chicken ovalbumin and the IgG fraction of rabbit anti-ovalbumin. Paramethasone, hydrocortisone, indomethacin, pirprofen, sulfinpyrazone, thalidomide and theophylline all gave significant inhibition of the RPAR. Ibuprofen, naproxen, cyprohepatadine and cromolyn sodium were inactive, while phenylbutazone and ASA exhibited a dose-dependent effect. The data show that the Arthus reaction, which is the result of the complex interaction of many factors, can be affected either generally or selectively at different time intervals by various therapeutic agents. The RPAR in rats may prove useful in detecting new therapeutic agents for the treatment of RA."} {"id": "PMID:157679", "title": "Humoral factors of local immunity in shigellosis.", "content": "Secretory immunoglobulins and antibodies were studied in dysentery patients of various age groups and in healthy persons. It is established that the level of IgA (mostly sIgA)) in coprofiltrates of patients is considerably increased and that the local production of sIgA starts very short (in 2--3 days) after the beginning of the disease. Specific coproantibodies are chiefly sIgA-antibodies. Increase of IgG in coprofiltrates is observed at early stages of the disease and is evidently due to transudation of serum proteins through the damaged mucosal membrane. High concentration of IgM is found mostly in coprofiltrates of children and is evidently the result of its local synthesis. -- Local immune response in shigellosis develops independently of systemic antibody formation. Increase of serum IgA level and appearance of sIgA-antibodies in sera of patients show the participation of local antibody forming system in formation of systemic immunity in intestinal infections.", "contents": "Humoral factors of local immunity in shigellosis. Secretory immunoglobulins and antibodies were studied in dysentery patients of various age groups and in healthy persons. It is established that the level of IgA (mostly sIgA)) in coprofiltrates of patients is considerably increased and that the local production of sIgA starts very short (in 2--3 days) after the beginning of the disease. Specific coproantibodies are chiefly sIgA-antibodies. Increase of IgG in coprofiltrates is observed at early stages of the disease and is evidently due to transudation of serum proteins through the damaged mucosal membrane. High concentration of IgM is found mostly in coprofiltrates of children and is evidently the result of its local synthesis. -- Local immune response in shigellosis develops independently of systemic antibody formation. Increase of serum IgA level and appearance of sIgA-antibodies in sera of patients show the participation of local antibody forming system in formation of systemic immunity in intestinal infections."} {"id": "PMID:157681", "title": "Examination of the immunocompetent cell composition of contact dermatitis. Methods for liberating infiltrative dermal cells and measuring antigen-dependent chromatin birefringence in them.", "content": "Infiltrating cells from the dermis can be literated without serious damage to the cell surface by cautious enzymatic treatment in a cell extractor. A new rapid method has been worked out measuring lymphocyte stimulation by detecting changes in the chromatin's birefringence. The chromatin's anisotropy depended upon antigen concentration, incubation time at 37 degrees and was unsignificantly influenced by the samples' cellularity, between 4 x 10(5) and 4 x 10(7) cells per ml. Therefore, it was concluded that the stimulated lymphocytes in the eczematous infiltrate can be detected by birefringence after incubating for 30 min with proper concentrations of the antigen.", "contents": "Examination of the immunocompetent cell composition of contact dermatitis. Methods for liberating infiltrative dermal cells and measuring antigen-dependent chromatin birefringence in them. Infiltrating cells from the dermis can be literated without serious damage to the cell surface by cautious enzymatic treatment in a cell extractor. A new rapid method has been worked out measuring lymphocyte stimulation by detecting changes in the chromatin's birefringence. The chromatin's anisotropy depended upon antigen concentration, incubation time at 37 degrees and was unsignificantly influenced by the samples' cellularity, between 4 x 10(5) and 4 x 10(7) cells per ml. Therefore, it was concluded that the stimulated lymphocytes in the eczematous infiltrate can be detected by birefringence after incubating for 30 min with proper concentrations of the antigen."} {"id": "PMID:157682", "title": "[On the influence of thiocyanates on the delayed immune response in intact and epinephrectomised guinea pigs (author's transl)].", "content": "Daily application of 32 mg/kg sodium thiocynate from 1--11th respectively 12th--21st experimental day causes in epinephrectomised guinea pigs at the 26th experimental day an inhibition of cell-mediated immune response (sensitization was induced by intraperitoneal injection of horse serum at the 5th and 7th experimental day). The inhibition of cell-mediated immune response could be demonstrated by means of migration inhibition of spleen cells. Epinephrectomy was performed by operation procedures twice a week. Gluco- and mineralocorticoids were applied supplementary. -- Also other proved thiocyanates respectively compounds with thiocyanate groups such as potassium thiocyanate, ammonium thiocyanate and d,1-2-imino-3.4-dimethyl-5-phenyl-thiacolidinhydrothiocyanate showed the same effect. The results are only pointed out in intact animals, but distinct in epinephrectomised guinea pigs. Finally a significant weaker effect, but of the same kind was observed by potassium- and sodium iodate. Every used dose of prednisolone and cyclophosphamide suppress the migration inhibition. The influence of 2-iminothiacolidin-4-carbon acid and desoxycorticosteronacetat on the migration inhibition is different and depends on the antigen dose applied for sensitization. -- Simulated daily injections undertaken in form of stitches and application of aqua destillata are inefficacious.", "contents": "[On the influence of thiocyanates on the delayed immune response in intact and epinephrectomised guinea pigs (author's transl)]. Daily application of 32 mg/kg sodium thiocynate from 1--11th respectively 12th--21st experimental day causes in epinephrectomised guinea pigs at the 26th experimental day an inhibition of cell-mediated immune response (sensitization was induced by intraperitoneal injection of horse serum at the 5th and 7th experimental day). The inhibition of cell-mediated immune response could be demonstrated by means of migration inhibition of spleen cells. Epinephrectomy was performed by operation procedures twice a week. Gluco- and mineralocorticoids were applied supplementary. -- Also other proved thiocyanates respectively compounds with thiocyanate groups such as potassium thiocyanate, ammonium thiocyanate and d,1-2-imino-3.4-dimethyl-5-phenyl-thiacolidinhydrothiocyanate showed the same effect. The results are only pointed out in intact animals, but distinct in epinephrectomised guinea pigs. Finally a significant weaker effect, but of the same kind was observed by potassium- and sodium iodate. Every used dose of prednisolone and cyclophosphamide suppress the migration inhibition. The influence of 2-iminothiacolidin-4-carbon acid and desoxycorticosteronacetat on the migration inhibition is different and depends on the antigen dose applied for sensitization. -- Simulated daily injections undertaken in form of stitches and application of aqua destillata are inefficacious."} {"id": "PMID:157683", "title": "[3H-thymidine-paper strip-counting of in vitro lymphocyte transformation. II. Specific antigens in the whole blood assay (author's transl)].", "content": "Erythrocytes did not influence the harvesting procedure or the paper strip counting method in a liquid scintillation counter using the whole blood assay of lymphocyte transformation test. The leucocyte-erythrocyte-ratio influences the blastogenesis in vitro. Only 1--2 ml of peripheral blood are necessary to proof lymphocyte reactivity to mitogens or antigens. The storage of the blood is possible over a period of 24 hours (4 degrees C) if the absolute lymphocytes count remains constant.", "contents": "[3H-thymidine-paper strip-counting of in vitro lymphocyte transformation. II. Specific antigens in the whole blood assay (author's transl)]. Erythrocytes did not influence the harvesting procedure or the paper strip counting method in a liquid scintillation counter using the whole blood assay of lymphocyte transformation test. The leucocyte-erythrocyte-ratio influences the blastogenesis in vitro. Only 1--2 ml of peripheral blood are necessary to proof lymphocyte reactivity to mitogens or antigens. The storage of the blood is possible over a period of 24 hours (4 degrees C) if the absolute lymphocytes count remains constant."} {"id": "PMID:157684", "title": "[Immunological investigations of house-dust and house-dust mites. Part III. A simplified basophil degranulation test. Preliminary communication (author's transl)].", "content": "The basophil degranulation test (BDT) after Shelley has been simplified and tried on patients allergic to house-dust or to house-dust mites. All 20 patients reacted to the mite extracts and 19 out of 20 to the house dust extracts. Out of 20 control persons 17 had negative results to the mite extract and 16 to the house-dust extract. The advantages of this new simplified method are discussed.", "contents": "[Immunological investigations of house-dust and house-dust mites. Part III. A simplified basophil degranulation test. Preliminary communication (author's transl)]. The basophil degranulation test (BDT) after Shelley has been simplified and tried on patients allergic to house-dust or to house-dust mites. All 20 patients reacted to the mite extracts and 19 out of 20 to the house dust extracts. Out of 20 control persons 17 had negative results to the mite extract and 16 to the house-dust extract. The advantages of this new simplified method are discussed."} {"id": "PMID:157685", "title": "[Studies on the control of IgM-antibody synthesis V. Affinity of anti-DNP antibodies in carps immunized with DNP-ficoll (author's transl)].", "content": "The dynamics of affinity of anti-DNP antibodies of carps immunized with T cell independent DNP-Ficoll was studied during the immune response. The intrinsic affinity (KO) of antibodies to monovalent epsilon-DNP-lysine is 10(5)--10(6)M-1 and does not change significantly in course of the immunisation. The affinity of tetrameric IgM antibodies to multivalent DNP-T4 conjugate is only 10(2)--10(3)-fold greater than to monovalent hapten, contrary to about 10(6)-fold higher values following immunisation with T cell-dependent antigens. The functional affinity (KF) increases during immune response slightly. KO and KF or antibodies are dependent on antigen dose. High antigen doses elicite antibodies with higher affinity.", "contents": "[Studies on the control of IgM-antibody synthesis V. Affinity of anti-DNP antibodies in carps immunized with DNP-ficoll (author's transl)]. The dynamics of affinity of anti-DNP antibodies of carps immunized with T cell independent DNP-Ficoll was studied during the immune response. The intrinsic affinity (KO) of antibodies to monovalent epsilon-DNP-lysine is 10(5)--10(6)M-1 and does not change significantly in course of the immunisation. The affinity of tetrameric IgM antibodies to multivalent DNP-T4 conjugate is only 10(2)--10(3)-fold greater than to monovalent hapten, contrary to about 10(6)-fold higher values following immunisation with T cell-dependent antigens. The functional affinity (KF) increases during immune response slightly. KO and KF or antibodies are dependent on antigen dose. High antigen doses elicite antibodies with higher affinity."} {"id": "PMID:157692", "title": "Elevation of ventricular defibrillation threshold in dogs by antiarrhythmic drugs.", "content": "Effects of antiarrhythmic drugs upon the threshold delivered energy (TDE) and threshold peak current (TPC) for electrical ventricular defibrillation by damped sinusoidal shocks were investigated in 25 pentobarbital-anesthetized dogs. TDE and TPC were increased by the three antiarrhytmic drugs tested. Bolus injections produced a transient rise and continuous infusions produced a steady rise in difibrillation threshold. The maximal percent elevations in mean defibrillation threshold during the 60 minutes after intravenous drug treatment in groups of n = 5 dogs were: (formula: see text). Accordingly, individuals receiving antiarrhythmic drugs who nonetheless fibrillate may require greater electric shock strength for defibrillation.", "contents": "Elevation of ventricular defibrillation threshold in dogs by antiarrhythmic drugs. Effects of antiarrhythmic drugs upon the threshold delivered energy (TDE) and threshold peak current (TPC) for electrical ventricular defibrillation by damped sinusoidal shocks were investigated in 25 pentobarbital-anesthetized dogs. TDE and TPC were increased by the three antiarrhytmic drugs tested. Bolus injections produced a transient rise and continuous infusions produced a steady rise in difibrillation threshold. The maximal percent elevations in mean defibrillation threshold during the 60 minutes after intravenous drug treatment in groups of n = 5 dogs were: (formula: see text). Accordingly, individuals receiving antiarrhythmic drugs who nonetheless fibrillate may require greater electric shock strength for defibrillation."} {"id": "PMID:157693", "title": "Ischemic heart disease secondary to amyloidosis of intramyocardial arteries.", "content": "Among 108 patients with cardiac amyloidosis studied at autopsy between 1889 and 1977 there were 5 (4.6 percent) with severe occlusive amyloid deposits in intramyocardial arteries. The hearts of all five patients showed focal subendocardial ischemic injury, and the vessels supplying these areas had either complete or near complete luminal obliteration by amyloid. Clinically, four patients had congestive heart failure; one of these patients also had arrhythmias and one had angina pectoris. Neither the clinical nor the pathologic features of ischemic heart diseases could be attributed to disease of the epicardial coronary arteries. Amyloidosis of the intramyocardial arteries appears to be capable of producing localized areas of ischemic necrosis and may produce intractable congestive heart failure due to multiple areas of ischemic injury.", "contents": "Ischemic heart disease secondary to amyloidosis of intramyocardial arteries. Among 108 patients with cardiac amyloidosis studied at autopsy between 1889 and 1977 there were 5 (4.6 percent) with severe occlusive amyloid deposits in intramyocardial arteries. The hearts of all five patients showed focal subendocardial ischemic injury, and the vessels supplying these areas had either complete or near complete luminal obliteration by amyloid. Clinically, four patients had congestive heart failure; one of these patients also had arrhythmias and one had angina pectoris. Neither the clinical nor the pathologic features of ischemic heart diseases could be attributed to disease of the epicardial coronary arteries. Amyloidosis of the intramyocardial arteries appears to be capable of producing localized areas of ischemic necrosis and may produce intractable congestive heart failure due to multiple areas of ischemic injury."} {"id": "PMID:157695", "title": "Dilatation of the descending aorta: a radiologic and echocardiographic diagnostic sign in arteriovenous malformations in neonates and young infants.", "content": "Eleven infants with arteriovenous malformations were admitted to St. Christopher's Hospital for Children between 1970 and 1978. Dilatation of the descending aorta was seen in the chest roentgenogram in 8 of the 11 patients. Echocardiography used in the two most recent cases revealed approximation of the descending aorta to the posterior left atrial and left ventricular wall in association with generalized cardiomegaly. The most frequently reported radiologic findings in infants with arteriovenous malformations are cardiomegaly, increased pulmonary vasculature and a widened superior mediastinum. These findings can accompany other congenital malformations of the heart, but the radiographic and echocardiographic findings of a dilated descending aorta appear to be more specifically associated with arteriovenous malformations in the neonate and infant.", "contents": "Dilatation of the descending aorta: a radiologic and echocardiographic diagnostic sign in arteriovenous malformations in neonates and young infants. Eleven infants with arteriovenous malformations were admitted to St. Christopher's Hospital for Children between 1970 and 1978. Dilatation of the descending aorta was seen in the chest roentgenogram in 8 of the 11 patients. Echocardiography used in the two most recent cases revealed approximation of the descending aorta to the posterior left atrial and left ventricular wall in association with generalized cardiomegaly. The most frequently reported radiologic findings in infants with arteriovenous malformations are cardiomegaly, increased pulmonary vasculature and a widened superior mediastinum. These findings can accompany other congenital malformations of the heart, but the radiographic and echocardiographic findings of a dilated descending aorta appear to be more specifically associated with arteriovenous malformations in the neonate and infant."} {"id": "PMID:157697", "title": "Reproductive risk of t(13q14q) carriers: case report and review.", "content": "We report a four-generation kindred with a balanced 13q14q Robertsonian translocation. The proband had the Down sydrome, due to trisomy of chromosome 21; he also carried the balanced D-group translocation. S segregation analysis of 86 sibships was performed to examine the risk of t(13q14q) carrier parents having trisomy 21, 47,XXY, or trisomy 13 children by which a number of families were ascertained. None of these disorders recurred after birth of the propositi. The frequency of abortions was not different from that of the general population. The conditional segregation ratio for balanced translocation carriers among the phenotypically normal offspring of carrier parents was 0.55 +/- 0.04.", "contents": "Reproductive risk of t(13q14q) carriers: case report and review. We report a four-generation kindred with a balanced 13q14q Robertsonian translocation. The proband had the Down sydrome, due to trisomy of chromosome 21; he also carried the balanced D-group translocation. S segregation analysis of 86 sibships was performed to examine the risk of t(13q14q) carrier parents having trisomy 21, 47,XXY, or trisomy 13 children by which a number of families were ascertained. None of these disorders recurred after birth of the propositi. The frequency of abortions was not different from that of the general population. The conditional segregation ratio for balanced translocation carriers among the phenotypically normal offspring of carrier parents was 0.55 +/- 0.04."} {"id": "PMID:157698", "title": "Electrocoagulation of pelvic endometriotic lesions with laparoscopic control.", "content": "Twenty-eight patients presenting with initial complaints of infertility or chronic pelvic pain were found to have pelvic endometriosis at laparoscopy. Destruction of the endometriotic lesions by means of electrocoagulation was performed via laparoscopy in a group of 19 patients. The remaining nine patients did not undergo such management. In the treatment group, seven of the 11 patients with chronic pain experienced complete relief of their symptoms, and six of the eight patients with infertility became pregnant postoperatively. Patients in the control group had a less favorable outcome. Only one of five patients with chronic pain had relief and one of four patients with infertility became pregnant following laparoscopy without cauterization. Electrocoagulation of pelvic endometriotic lesions under laparoscopic control appears to be satisfactory for the management of selected patients with chronic pelvic pain or infertility.", "contents": "Electrocoagulation of pelvic endometriotic lesions with laparoscopic control. Twenty-eight patients presenting with initial complaints of infertility or chronic pelvic pain were found to have pelvic endometriosis at laparoscopy. Destruction of the endometriotic lesions by means of electrocoagulation was performed via laparoscopy in a group of 19 patients. The remaining nine patients did not undergo such management. In the treatment group, seven of the 11 patients with chronic pain experienced complete relief of their symptoms, and six of the eight patients with infertility became pregnant postoperatively. Patients in the control group had a less favorable outcome. Only one of five patients with chronic pain had relief and one of four patients with infertility became pregnant following laparoscopy without cauterization. Electrocoagulation of pelvic endometriotic lesions under laparoscopic control appears to be satisfactory for the management of selected patients with chronic pelvic pain or infertility."} {"id": "PMID:157699", "title": "Acid mucopolysaccharides of congenitally defective, rheumatic, and normal human aortic valves.", "content": "The qualitative nature, total amount, and relative proportion of various acid mucopolysaccharides (AMPSs) found in congenitally defective (bicuspid), young rheumatic, and normal aortic valvular tissue were compared. No differences in the qualitative nature of AMPSs were found in any of the aortic tissues studies; hyaluronic acid, chondroitin sulfate B, and chondroitin sulfate A/C were the primary AMPS components, with a trace amount of heparin. Congenitally defective aortic valves showed increasing amounts of calcification, a lowering of total AMPS content, and an alteration in the relative proportions of various AMPS with advancing age, as compared with age-matched normal aortic valves. The total AMPS content of rheumatic aortic valves from individuals under the age of 21 years was found to be significantly higher than that of age-matched normal controls. In addition, these rheumatic aortic valves showed an alteration in AMPS composition that was similar to that of congenitally defective aortic valves obtained from older individuals. These observations suggest nonspecific changes in the AMPS composition caused by chronic tissue damage, calcification, and fibrosis.", "contents": "Acid mucopolysaccharides of congenitally defective, rheumatic, and normal human aortic valves. The qualitative nature, total amount, and relative proportion of various acid mucopolysaccharides (AMPSs) found in congenitally defective (bicuspid), young rheumatic, and normal aortic valvular tissue were compared. No differences in the qualitative nature of AMPSs were found in any of the aortic tissues studies; hyaluronic acid, chondroitin sulfate B, and chondroitin sulfate A/C were the primary AMPS components, with a trace amount of heparin. Congenitally defective aortic valves showed increasing amounts of calcification, a lowering of total AMPS content, and an alteration in the relative proportions of various AMPS with advancing age, as compared with age-matched normal aortic valves. The total AMPS content of rheumatic aortic valves from individuals under the age of 21 years was found to be significantly higher than that of age-matched normal controls. In addition, these rheumatic aortic valves showed an alteration in AMPS composition that was similar to that of congenitally defective aortic valves obtained from older individuals. These observations suggest nonspecific changes in the AMPS composition caused by chronic tissue damage, calcification, and fibrosis."} {"id": "PMID:157700", "title": "Pediatric cancer survival and marriage: issues affecting adult adjustment.", "content": "Of 36 men and women, now aged 21 or older, who were treated for cancer as children, 20 have married. As part of a long-term follow-up, 13 of their spouses were interviewed about the effects of cancer on the patient and on their marriage. Comparison of patient's physical limitations, visible impairments, and psychiatric adjustment ratings indicated significant differences between patients who have married or become engaged and those who have not married.", "contents": "Pediatric cancer survival and marriage: issues affecting adult adjustment. Of 36 men and women, now aged 21 or older, who were treated for cancer as children, 20 have married. As part of a long-term follow-up, 13 of their spouses were interviewed about the effects of cancer on the patient and on their marriage. Comparison of patient's physical limitations, visible impairments, and psychiatric adjustment ratings indicated significant differences between patients who have married or become engaged and those who have not married."} {"id": "PMID:157704", "title": "The ultrastructure of the capsule of the neuromuscular spindles from Python reticulatus (Schneid.).", "content": "The capsule of the neuromuscular spindles in the lower costocutaneous muscles from Python reticulatus (Schneid.) has been studied at the electron microscope. As in other vertebrate species, the capsule is divisible into 2 components, i.e. an inner and an outer capsule, which display a very similar structure. Moreover, it has been possible to bring to light the continuity of the outer capsule with the cells and fibres of the perineural sheath enveloping the sensory and motory fibres. The capsule cells exhibit a number of pinocytotic vesicles, profiles of granular endoplasmic reticulum, mitochondria, glycogen particles and Golgi complexes. The presence of these structures points to the secretory and transport activities performed by the spindle capsule in the control of the composition of the intracapsular fluid.", "contents": "The ultrastructure of the capsule of the neuromuscular spindles from Python reticulatus (Schneid.). The capsule of the neuromuscular spindles in the lower costocutaneous muscles from Python reticulatus (Schneid.) has been studied at the electron microscope. As in other vertebrate species, the capsule is divisible into 2 components, i.e. an inner and an outer capsule, which display a very similar structure. Moreover, it has been possible to bring to light the continuity of the outer capsule with the cells and fibres of the perineural sheath enveloping the sensory and motory fibres. The capsule cells exhibit a number of pinocytotic vesicles, profiles of granular endoplasmic reticulum, mitochondria, glycogen particles and Golgi complexes. The presence of these structures points to the secretory and transport activities performed by the spindle capsule in the control of the composition of the intracapsular fluid."} {"id": "PMID:157705", "title": "Efficacy of albendazole for treatment of naturally acquired nematode infections in Washington cattle.", "content": "Albendazole, methyl 5-propylthio-1H-benzimidazol-2-yl carbamate, was given as a bolus (7.68 to 8.18 mg/kg of body weight) to cattle naturally infected with gastrointestinal nematodes and lungworms in a controlled trial. Over 99% of adult Ostertagia ostertagi, Trichostrongylus longispicularis, Cooperia oncophora, Nematodirus helvetianus, and Dictyocaulus viviparus were removed by the treatment. Efficacy against immature O ostertagi, early fourth-stage O ostertagi, and Oesophagostomum radiatum was 95.2%, 86.6%, and 96.7%, respectively. In a field trial, the same compound administered in a paste formulation (at approximately 7.5 mg/kg) eliminated over 99% of strongylin and Moniezia eggs from feces of treated cattle.", "contents": "Efficacy of albendazole for treatment of naturally acquired nematode infections in Washington cattle. Albendazole, methyl 5-propylthio-1H-benzimidazol-2-yl carbamate, was given as a bolus (7.68 to 8.18 mg/kg of body weight) to cattle naturally infected with gastrointestinal nematodes and lungworms in a controlled trial. Over 99% of adult Ostertagia ostertagi, Trichostrongylus longispicularis, Cooperia oncophora, Nematodirus helvetianus, and Dictyocaulus viviparus were removed by the treatment. Efficacy against immature O ostertagi, early fourth-stage O ostertagi, and Oesophagostomum radiatum was 95.2%, 86.6%, and 96.7%, respectively. In a field trial, the same compound administered in a paste formulation (at approximately 7.5 mg/kg) eliminated over 99% of strongylin and Moniezia eggs from feces of treated cattle."} {"id": "PMID:157706", "title": "[Two new cases of allergy to tartrazine (author's transl)].", "content": "Two patients developed allergy to tartrazine, and the symptoms, as in most such cases, were related to the skin and mucous membranes. The clinical diagnosis was confirmed by the basophil degranulation test. These observations underline the intrication of food substances and medications in the genesis of these accidents and demonstrate the notion of a quantitative contribution of food additives. The author discusses the frequency of these allergies to this colouring substance, and restates the position, which has just been taken by the Academy of Medicine, with the objective of prohibiting the use of tartrazine E 102 in food substances.", "contents": "[Two new cases of allergy to tartrazine (author's transl)]. Two patients developed allergy to tartrazine, and the symptoms, as in most such cases, were related to the skin and mucous membranes. The clinical diagnosis was confirmed by the basophil degranulation test. These observations underline the intrication of food substances and medications in the genesis of these accidents and demonstrate the notion of a quantitative contribution of food additives. The author discusses the frequency of these allergies to this colouring substance, and restates the position, which has just been taken by the Academy of Medicine, with the objective of prohibiting the use of tartrazine E 102 in food substances."} {"id": "PMID:157709", "title": "Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features.", "content": "Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree.", "contents": "Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features. Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree."} {"id": "PMID:157710", "title": "Adenylate cyclase in muscular dystrophy.", "content": "The purpose of this study was to determine whether the previously reported differences in adenylate cyclase activity between the sarcolemma of normal and dystrophic chick muscles are also found in the SR, to search for a possible relationship between the adenylate cyclase changes and the pathophysiology of dystrophy, and to investigate whether the findings can be extended to Duchenne human muscular dystrophy by studying the adenylate cyclase and ATPase activities of erythrocyte ghosts from DMD patients and carriers. Microsomes were separated by standard techniques from the pectoralis muscles of normal and dystrophic ckeckens of various ages. The microsomal yields were significantly larger in dystrophic muscles. Adenylate cyclase activities in dystrophic microsomes were higher than those in matched controls and increased with the progression of the disease. The ratio between the two rose from one at 2 weeks of age to nine at about 9--10 weeks. Kinetic analyses showed that the ks for MgATP2- was about 40 microM (at 3 mM Mg2+ and 0.3 mM Ca2+) both in normal and dystrophic microsomes, that calcium caused umcompetitive inhibition of the enzyme (Ki = 0.2 mM), that the effect of calcium was noncooperative (Hill coefficient, nH = 1), that calcium did not affect the cooperativity for MgATP2-, and that magnesium competitively removed the calcium inhibition and caused additional, cooperative stimulation of the enzymatic activity (ka = 1.5 mM; NH =2). The major difference between normal and dystrophic adenylate cyclase was a higher enzymatic velocity in the latter, suggesting a larger amount of enzyme. We investigated whether altered cAMP levels may effect calcium accumulation. Calcium uptake measured (in the presence of oxalate) at several ages revealed no difference between normal and dystrophic chickens. The extent of calcium binding was also similar, although the kd for Ca2+ was lower in dystrophic microsomes. Binding was enhanced in the presence of exogenous protein kinase, but the responses of normal and dystrophic tissues were similar. We concluded that the elevation of adenylate cyclase in dystrophy was not related to microsomal calcium accumultion. Ivestigation of the localization of microsomal adenylate cyclase supported this view. Separation of calcium-loaded microsomes on a discontinuous sucrose gradient into four fractions demonstrated that adenylate cyclase activity, measured in the presence of Lubrol-PX and EGTA, was inversely related to calcium-accumulating activity. Na+, K+-ATPase comigrated with adenylate cyclase. Highest specific activities were found in the lightest fraction. These observations were confirmed by histochemical studies. The reaction product from adenylate cyclase activity was present predominantly in the terminal cisternae of the SR. In the context of the literature, our findings suggest that the rises in adenylate cyclase and Na+, K+-ATPase in avian dystrophy are compensatory changes, elicited by a defect in ECC at the calcium release step...", "contents": "Adenylate cyclase in muscular dystrophy. The purpose of this study was to determine whether the previously reported differences in adenylate cyclase activity between the sarcolemma of normal and dystrophic chick muscles are also found in the SR, to search for a possible relationship between the adenylate cyclase changes and the pathophysiology of dystrophy, and to investigate whether the findings can be extended to Duchenne human muscular dystrophy by studying the adenylate cyclase and ATPase activities of erythrocyte ghosts from DMD patients and carriers. Microsomes were separated by standard techniques from the pectoralis muscles of normal and dystrophic ckeckens of various ages. The microsomal yields were significantly larger in dystrophic muscles. Adenylate cyclase activities in dystrophic microsomes were higher than those in matched controls and increased with the progression of the disease. The ratio between the two rose from one at 2 weeks of age to nine at about 9--10 weeks. Kinetic analyses showed that the ks for MgATP2- was about 40 microM (at 3 mM Mg2+ and 0.3 mM Ca2+) both in normal and dystrophic microsomes, that calcium caused umcompetitive inhibition of the enzyme (Ki = 0.2 mM), that the effect of calcium was noncooperative (Hill coefficient, nH = 1), that calcium did not affect the cooperativity for MgATP2-, and that magnesium competitively removed the calcium inhibition and caused additional, cooperative stimulation of the enzymatic activity (ka = 1.5 mM; NH =2). The major difference between normal and dystrophic adenylate cyclase was a higher enzymatic velocity in the latter, suggesting a larger amount of enzyme. We investigated whether altered cAMP levels may effect calcium accumulation. Calcium uptake measured (in the presence of oxalate) at several ages revealed no difference between normal and dystrophic chickens. The extent of calcium binding was also similar, although the kd for Ca2+ was lower in dystrophic microsomes. Binding was enhanced in the presence of exogenous protein kinase, but the responses of normal and dystrophic tissues were similar. We concluded that the elevation of adenylate cyclase in dystrophy was not related to microsomal calcium accumultion. Ivestigation of the localization of microsomal adenylate cyclase supported this view. Separation of calcium-loaded microsomes on a discontinuous sucrose gradient into four fractions demonstrated that adenylate cyclase activity, measured in the presence of Lubrol-PX and EGTA, was inversely related to calcium-accumulating activity. Na+, K+-ATPase comigrated with adenylate cyclase. Highest specific activities were found in the lightest fraction. These observations were confirmed by histochemical studies. The reaction product from adenylate cyclase activity was present predominantly in the terminal cisternae of the SR. In the context of the literature, our findings suggest that the rises in adenylate cyclase and Na+, K+-ATPase in avian dystrophy are compensatory changes, elicited by a defect in ECC at the calcium release step..."} {"id": "PMID:157711", "title": "[Metronidazole therapy in rosacea (author's transl)].", "content": "Metronidazole was administered (500 mg daily the first month, 250 mg daily the second month and, in some cases, 250 mg every other day the following months) to 62 patients suffering from rosacea or perioral dermatitis. 90 p. 100 of them improved within 2 months and Metronidazole was particularly effective against papulo-pustules. Relapses after interruption of treatment seemed to be less frequent than with Tetracycline therapy. Side-effects (gastro-intestinal disturbances) occurred in few patients but long-term tolerance remains uncertain. So, the length of treatment was less than 6 months and the drug was not given to pregnant women.", "contents": "[Metronidazole therapy in rosacea (author's transl)]. Metronidazole was administered (500 mg daily the first month, 250 mg daily the second month and, in some cases, 250 mg every other day the following months) to 62 patients suffering from rosacea or perioral dermatitis. 90 p. 100 of them improved within 2 months and Metronidazole was particularly effective against papulo-pustules. Relapses after interruption of treatment seemed to be less frequent than with Tetracycline therapy. Side-effects (gastro-intestinal disturbances) occurred in few patients but long-term tolerance remains uncertain. So, the length of treatment was less than 6 months and the drug was not given to pregnant women."} {"id": "PMID:157707", "title": "[Studies on the conidial differentiation of \"Neurospora crassa\" -- VII. -- Alcoholic regulation and conidiogenous capacity (wild-type and \"fluffy\" mutant) (authors transl)].", "content": "Sucrose consumption by the wild-type Neurospora crassa is quicker, with much more ethanol produced, in the ammonium medium than in nitrate as single N source. On low sugar concentration which is quickly nullified, little alcohol is produced and early conidiation can develop. The higher the initial sugar concentration, the higher is the alcoholigenic coefficient defined as the efficiency of alcoholic glycolysis per unit of sugar consumed, and the more complete is the conidial \"repression\" in ammonium medium. The nitrate counteracts this catabolic repression effect and, depressing the alcoholigenic coefficients, permits conidiation even on high sugar (8 %) medium. The \"fluffy\" mutant produces relatively less ethanol (average 2-3 times less) in all cases even though it increases its alcoholigenic coefficient with the increased sugar concentration. Surprisingly, it is not induced to alcoholigenic glycolytic disinhibition by ammonium and produces even more alcohol in nitrate than in ammonium media, thus revealing an inability to benefit from the antiglycolytic, normally conidiogenous, effect of nitrate. Suggestion is made that this amacroconidial mutant is defective in its metabolic regulation related to the Pasteur effect which is required for conidiogenic expression in the wild type.", "contents": "[Studies on the conidial differentiation of \"Neurospora crassa\" -- VII. -- Alcoholic regulation and conidiogenous capacity (wild-type and \"fluffy\" mutant) (authors transl)]. Sucrose consumption by the wild-type Neurospora crassa is quicker, with much more ethanol produced, in the ammonium medium than in nitrate as single N source. On low sugar concentration which is quickly nullified, little alcohol is produced and early conidiation can develop. The higher the initial sugar concentration, the higher is the alcoholigenic coefficient defined as the efficiency of alcoholic glycolysis per unit of sugar consumed, and the more complete is the conidial \"repression\" in ammonium medium. The nitrate counteracts this catabolic repression effect and, depressing the alcoholigenic coefficients, permits conidiation even on high sugar (8 %) medium. The \"fluffy\" mutant produces relatively less ethanol (average 2-3 times less) in all cases even though it increases its alcoholigenic coefficient with the increased sugar concentration. Surprisingly, it is not induced to alcoholigenic glycolytic disinhibition by ammonium and produces even more alcohol in nitrate than in ammonium media, thus revealing an inability to benefit from the antiglycolytic, normally conidiogenous, effect of nitrate. Suggestion is made that this amacroconidial mutant is defective in its metabolic regulation related to the Pasteur effect which is required for conidiogenic expression in the wild type."} {"id": "PMID:157723", "title": "[Oral treatment with tretinoin: andrological, trichological, ophthalmological findings and effects on acne (author's transl)].", "content": "Twelve patients (20 +/- 2 years) with acne vulgaris were treated orally with 20-30 mg/day tretinoin (vitamin A acid) over 90-300 days. Various laboratory tests were performed to rule out unwanted pharmacological side effects. Tretinoin therapy was well tolerated except for minor complaints of dryness around the mucous membranes of mouth and nose. The acne remained unchanged. All laboratory tests were unremarkable except for a significant rise of ejaculate volume. Other sperm parameters, trichological, ophthalmological as well as blood and urine analyses showed no measurable effects of tretinoin therapy.", "contents": "[Oral treatment with tretinoin: andrological, trichological, ophthalmological findings and effects on acne (author's transl)]. Twelve patients (20 +/- 2 years) with acne vulgaris were treated orally with 20-30 mg/day tretinoin (vitamin A acid) over 90-300 days. Various laboratory tests were performed to rule out unwanted pharmacological side effects. Tretinoin therapy was well tolerated except for minor complaints of dryness around the mucous membranes of mouth and nose. The acne remained unchanged. All laboratory tests were unremarkable except for a significant rise of ejaculate volume. Other sperm parameters, trichological, ophthalmological as well as blood and urine analyses showed no measurable effects of tretinoin therapy."} {"id": "PMID:157726", "title": "[Risks and long-term results or tricuspid monovalvular replacement, using a ball or disk prosthesis. Apropos of 21 cases].", "content": "21 patients (15 with stage IV and 6 with stage III symptoms by the NYHA classification) underwent monovalvular tricuspid replacement with a ball or disc prosthesis for varying tricuspid pathology, bacterial endocarditis in half the cases, between June 1964 and July 1973. Hospital mortality was 29 p. 100 (6 patients), medium-term mortality, nil. There were 23 survivors (62 p. 100) with an average follow up of 7 years (range 5 years to 10 years 4 months), 12 of whom recovered to stage I disability by the NYHA classification after the first postoperative year. 12 patients are on long-term anticoagulant therapy and 3 on diuretic or digitalo-diuretic therapy. The main complications observed were 2 prosthetic thromboses and 3 haemorrhages for 1095 patient-months. The results are to be compared with those bioprostheses, which, not requiring anti-coagulant therapy, may tend to supplant ball and disc prostheses.", "contents": "[Risks and long-term results or tricuspid monovalvular replacement, using a ball or disk prosthesis. Apropos of 21 cases]. 21 patients (15 with stage IV and 6 with stage III symptoms by the NYHA classification) underwent monovalvular tricuspid replacement with a ball or disc prosthesis for varying tricuspid pathology, bacterial endocarditis in half the cases, between June 1964 and July 1973. Hospital mortality was 29 p. 100 (6 patients), medium-term mortality, nil. There were 23 survivors (62 p. 100) with an average follow up of 7 years (range 5 years to 10 years 4 months), 12 of whom recovered to stage I disability by the NYHA classification after the first postoperative year. 12 patients are on long-term anticoagulant therapy and 3 on diuretic or digitalo-diuretic therapy. The main complications observed were 2 prosthetic thromboses and 3 haemorrhages for 1095 patient-months. The results are to be compared with those bioprostheses, which, not requiring anti-coagulant therapy, may tend to supplant ball and disc prostheses."} {"id": "PMID:157727", "title": "Microbiological transformations. XI. The use of immobilized Rhodotorula mucilaginosa cells to reduce some ketones.", "content": "Rhodotorula mucilaginosa cells were immobilized by polymerizing acrylamide with the addition of a cross-linked agent, a catalyst and an initiator. This gel was used for the stereospecific reduction of acetophenone and alpha-acetylnaphthalene resulting chromatographically pure alcohols with absolute configuration S. When karen-3-dion-2,5 was used as substrate, four products were obtained. Androstenolone was reduced with 30% yield. Activity of the immobilized cells could be regenerated by glucose.", "contents": "Microbiological transformations. XI. The use of immobilized Rhodotorula mucilaginosa cells to reduce some ketones. Rhodotorula mucilaginosa cells were immobilized by polymerizing acrylamide with the addition of a cross-linked agent, a catalyst and an initiator. This gel was used for the stereospecific reduction of acetophenone and alpha-acetylnaphthalene resulting chromatographically pure alcohols with absolute configuration S. When karen-3-dion-2,5 was used as substrate, four products were obtained. Androstenolone was reduced with 30% yield. Activity of the immobilized cells could be regenerated by glucose."} {"id": "PMID:157724", "title": "[Pulmonary atresia with intact interventricular partition wall. Surgical treatment of a case with duramater ceiling].", "content": "It is presented a pulmonary artresia case with untouched interventricular partition wall surgically treated. It was established the continuity between right ventricle and pulmonary artery's trunk with duramater ceiling, for which it was made a pulmonary valve. Postoperation evolution was excelent and it was obteined a frank diminution of the right ventricle's systolic pression. It is discussed about therapeutic conducts in this kind of congenital badformation.", "contents": "[Pulmonary atresia with intact interventricular partition wall. Surgical treatment of a case with duramater ceiling]. It is presented a pulmonary artresia case with untouched interventricular partition wall surgically treated. It was established the continuity between right ventricle and pulmonary artery's trunk with duramater ceiling, for which it was made a pulmonary valve. Postoperation evolution was excelent and it was obteined a frank diminution of the right ventricle's systolic pression. It is discussed about therapeutic conducts in this kind of congenital badformation."} {"id": "PMID:157729", "title": "Outcome of comprehensive medical rehabilitation: measurement by PULSES profile and the Barthel Index.", "content": "In view of current emphasis on evaluation of benefits derived from rehabilitation programs, it is important that there be easily replicated measures for demonstrating the efficiency and effectiveness of services provided, as well as for transmitting information on patient functional status when transferring service responsibilities from one agency or facility to another. The authors used the PULSES profile and the Barthel index to measure severity of disability and to monitor rehabilitation progress in a heterogeneous sample of 307 severely disabled persons in 10 comprehensive medical rehabilitation centers, geographically selected. Gains in functional independence were registered for up to 2 years after admission. Cutting points of PULSES score totals or Barthel score totals distinguished the degree of severity of disability. The 2 scoring modalities appear valid, reliable, and sensitive for describing functional abilities and change over a period of time. They can be applied both to medical records and direct observations, and staff of medical facilities can readily be trained in their use.", "contents": "Outcome of comprehensive medical rehabilitation: measurement by PULSES profile and the Barthel Index. In view of current emphasis on evaluation of benefits derived from rehabilitation programs, it is important that there be easily replicated measures for demonstrating the efficiency and effectiveness of services provided, as well as for transmitting information on patient functional status when transferring service responsibilities from one agency or facility to another. The authors used the PULSES profile and the Barthel index to measure severity of disability and to monitor rehabilitation progress in a heterogeneous sample of 307 severely disabled persons in 10 comprehensive medical rehabilitation centers, geographically selected. Gains in functional independence were registered for up to 2 years after admission. Cutting points of PULSES score totals or Barthel score totals distinguished the degree of severity of disability. The 2 scoring modalities appear valid, reliable, and sensitive for describing functional abilities and change over a period of time. They can be applied both to medical records and direct observations, and staff of medical facilities can readily be trained in their use."} {"id": "PMID:157725", "title": "[Corrected transposition of the great arteries without associated abnormalities].", "content": "We studied 5 cases of corrected tansposition of big arteries without associated defects. Four of them showed situs solitus with apex to the left, and the fifth one showed dextroversion. In four of the cases the second sound was the only one, strong and to the left of the precordium; in four we found mild sistolic murmur in the third left intercostal space. In all of them, XR plates showed the largest liver lobe to the left, apex to the left in four and to the right in one, being possible to see the ascending aorta to the left in four cases. A patient with complete auriculoventricular block showed cardiomegaly and excavated middle arch. Three of them presented sinusal rithm, one had auriculoventricular block of variable degree and the last had complete auriculoventricular block. In four cases the AQRS showed a deviation to the left, and the other one to the right. In the foreground of the first septal vector was going from right to left. The analysis of the unipolar and thoracic morphologies had alterations in the intraventricular conduction which suggested a right branch block in derivations exploring the ventricle located to the left and potential QS in the right pre-cordials. We found a pattern of sistolic overload of the sistemic ventricle. Through determination made by the His Ecg we found that the alterations in conduction were distal. The electro-mechanic latent period of the ventricle located to the right was shorter than the opposite. The angiographic studio helped to establish the auriculoventricular discordant relations and to identify the ventricles position through their angiographic morphology. In the cases showing point to the left, the ventricle anatomically considered as the left one showed a triangular form and smooth walls, while the ventricle anatomically consider being the right one presented trabeculated walls. In dextroversion the anatomically left ventricle was egg-shaped with smooth walls. All of them presented the aorta above the pulmonar artery.", "contents": "[Corrected transposition of the great arteries without associated abnormalities]. We studied 5 cases of corrected tansposition of big arteries without associated defects. Four of them showed situs solitus with apex to the left, and the fifth one showed dextroversion. In four of the cases the second sound was the only one, strong and to the left of the precordium; in four we found mild sistolic murmur in the third left intercostal space. In all of them, XR plates showed the largest liver lobe to the left, apex to the left in four and to the right in one, being possible to see the ascending aorta to the left in four cases. A patient with complete auriculoventricular block showed cardiomegaly and excavated middle arch. Three of them presented sinusal rithm, one had auriculoventricular block of variable degree and the last had complete auriculoventricular block. In four cases the AQRS showed a deviation to the left, and the other one to the right. In the foreground of the first septal vector was going from right to left. The analysis of the unipolar and thoracic morphologies had alterations in the intraventricular conduction which suggested a right branch block in derivations exploring the ventricle located to the left and potential QS in the right pre-cordials. We found a pattern of sistolic overload of the sistemic ventricle. Through determination made by the His Ecg we found that the alterations in conduction were distal. The electro-mechanic latent period of the ventricle located to the right was shorter than the opposite. The angiographic studio helped to establish the auriculoventricular discordant relations and to identify the ventricles position through their angiographic morphology. In the cases showing point to the left, the ventricle anatomically considered as the left one showed a triangular form and smooth walls, while the ventricle anatomically consider being the right one presented trabeculated walls. In dextroversion the anatomically left ventricle was egg-shaped with smooth walls. All of them presented the aorta above the pulmonar artery."} {"id": "PMID:157730", "title": "Morphometric comparison of capillaries in muscle spindles, nerve, and muscle.", "content": "Morphometric study was performed on transverse sections of microdissected muscle spindles from rabbit tenuissimus muscles. It showed a statistically significant difference in size and structure between the intrafusal capillaries and those of extrafusal muscle. The former are larger in diameter, circumference, and area due to a proportionate increase in the number of endothelial cells. Vesicles within spindle endothelial cells are fewer, mitochondrial counts are greater, but in proportion to the increased number of endothelial cells, intercellular junctions are tight and pericyte coverage is greater. The basement membrane around endothelial cells and pericytes is thicker and more often multilayered. The endoneurial capillaries of tenuissimus intramuscular nerve are morphologically identical to intrafusal capillaries. The similarity of the capillaries of spindles to those in brain suggests that a blood-nervous system barrier extends from brain into the peripheral nerves and muscle spindles.", "contents": "Morphometric comparison of capillaries in muscle spindles, nerve, and muscle. Morphometric study was performed on transverse sections of microdissected muscle spindles from rabbit tenuissimus muscles. It showed a statistically significant difference in size and structure between the intrafusal capillaries and those of extrafusal muscle. The former are larger in diameter, circumference, and area due to a proportionate increase in the number of endothelial cells. Vesicles within spindle endothelial cells are fewer, mitochondrial counts are greater, but in proportion to the increased number of endothelial cells, intercellular junctions are tight and pericyte coverage is greater. The basement membrane around endothelial cells and pericytes is thicker and more often multilayered. The endoneurial capillaries of tenuissimus intramuscular nerve are morphologically identical to intrafusal capillaries. The similarity of the capillaries of spindles to those in brain suggests that a blood-nervous system barrier extends from brain into the peripheral nerves and muscle spindles."} {"id": "PMID:157731", "title": "Chalazia and rosacea.", "content": "Fifty-seven percent of patients scheduled for excision of chalazia over 19 years of age and 64% of patients over the age of 29 were found to have rosacea. This compares to an incidence in our control group of 12% and 13%, respectively. Rosacea was almost twice as common in patients with recurrent chalazia as in those with only one occurrence.", "contents": "Chalazia and rosacea. Fifty-seven percent of patients scheduled for excision of chalazia over 19 years of age and 64% of patients over the age of 29 were found to have rosacea. This compares to an incidence in our control group of 12% and 13%, respectively. Rosacea was almost twice as common in patients with recurrent chalazia as in those with only one occurrence."} {"id": "PMID:157735", "title": "Effect of neocarzinostatin on the nucleus, kinetoplast and microtubules of Trypanosoma gambiense and Trypanosoma evansi.", "content": "The antibiotic neocarzinostatin (NCS) induces the anucleate form, not the dyskinetoplastic form, of Trypanosoma gambiense and Trypanosoma evansi. Light and electron microscopic studies indicated that production of the anucleate form is due to delay or inhibition of nuclear division. Excess pellicular microtubules are formed after treatment of trypanosomes with NCS, suggesting that in trypanosomes the microtubules replicate by induction, not by division. NCS also causes deformation of the axonemal and spindle microtubules. The K clone of T. evansi is more sensitive than the AK clone to the effects of NCS in inhibiting nuclear division and inducing the anucleate form.", "contents": "Effect of neocarzinostatin on the nucleus, kinetoplast and microtubules of Trypanosoma gambiense and Trypanosoma evansi. The antibiotic neocarzinostatin (NCS) induces the anucleate form, not the dyskinetoplastic form, of Trypanosoma gambiense and Trypanosoma evansi. Light and electron microscopic studies indicated that production of the anucleate form is due to delay or inhibition of nuclear division. Excess pellicular microtubules are formed after treatment of trypanosomes with NCS, suggesting that in trypanosomes the microtubules replicate by induction, not by division. NCS also causes deformation of the axonemal and spindle microtubules. The K clone of T. evansi is more sensitive than the AK clone to the effects of NCS in inhibiting nuclear division and inducing the anucleate form."} {"id": "PMID:157736", "title": "Cross-linking experiments with the adenosine triphosphatase of sarcoplasmic reticulum.", "content": "The proteins of sarcoplasmic reticulum were cross-linked by rapid oxidation of thiol groups with I2. About two-thirds of the thiols were oxidized without any significant cross-linking, implying an extensive formation of intramolecular disulphide bonds. When the thiols were completely oxidized at room temperature a series of oligomers containing up to five molecules were observed, as well as large aggregates which were excluded from the gels. Complete oxidation at -10 degrees C left most of the ATPase (adenosine triphosphatase) as monomer. Similar results were obtained when copper-phenanthroline complexes or dimethyl suberimidate were used as cross-linking reagents. We conclude that most of the cross-linked species arise by linking of randomly colliding ATPase molecules which are present in the membrane at very high concentration.", "contents": "Cross-linking experiments with the adenosine triphosphatase of sarcoplasmic reticulum. The proteins of sarcoplasmic reticulum were cross-linked by rapid oxidation of thiol groups with I2. About two-thirds of the thiols were oxidized without any significant cross-linking, implying an extensive formation of intramolecular disulphide bonds. When the thiols were completely oxidized at room temperature a series of oligomers containing up to five molecules were observed, as well as large aggregates which were excluded from the gels. Complete oxidation at -10 degrees C left most of the ATPase (adenosine triphosphatase) as monomer. Similar results were obtained when copper-phenanthroline complexes or dimethyl suberimidate were used as cross-linking reagents. We conclude that most of the cross-linked species arise by linking of randomly colliding ATPase molecules which are present in the membrane at very high concentration."} {"id": "PMID:157737", "title": "Identification of N-sulphated disaccharide units in heparin-like polysaccharides.", "content": "1. Preparations of heparin and heparan sulphate were degraded with HNO2. The resulting disaccharides were isolated by gel chromatography, reduced with either NaBH4 or NaB3H4 and were then fractionated into non-sulphated, monosulphated and disulphated species by ion-exchange chromatography or by paper electrophoresis. The non-sulphated disaccharides were separated into two, and the monosulphated disaccharides into three, components by paper chromatography. 2. The uronic acid moieties of the various non- and mono-sulphated disaccharides were identified by means of radioactive labels selectively introduced into uronic acid residues (3H and 14C in D-glucuronic acid, 14C only in L-iduronic acid units) during biosynthesis of the polysaccharide starting material. Labelled uronic acids were also identified by paper chromatography, after liberation from disaccharides by acid hydrolysis or by glucuronidase digestion. Similar procedures, applied to disaccharides treated with NaB3H4, indicated 2,5-anhydro-D-mannitol as reducing terminal unit. On the basis of these results, and the known positions and configurations of the glycosidic linkages in heparin, the two non-sulphated disaccharides were identified as 4-O-(beta-D-glucopyranosyluronic acid)-2,5-anhydro-D-mannitol and 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol. 3. The three monosulphated [1-3H]anhydromannitol-labelled disaccharides were subjected to Smith degradation or to digestion with homogenates of human skin fibroblasts, and the products were analysed by paper electrophoresis. The results, along with the 1H n.m.r. spectra of the corresponding unlabelled disaccharides, permitted the allocation of O-sulphate groups to various positions in the disaccharides. These were thus identified as 4-O-(beta-D-glucopyranosyl-uronic acid)-2,5-anhydro-D-mannitol 6-sulphate, 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol 6-sulphate and 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol. The last-mentioned disaccharide was found to be a poor substrate for the iduronate sulphatase of human skin fibroblasts, as compared with the disulphated species, 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol 6-sulphate. 4. The identified [1-3H]anhydromannitol-labelled disaccharides were used as reference standards in a study of the disaccharide composition of heparins and heparan sulphates. Low N-sulphate contents, most pronounced in the heparin sulphates, were associated with high ratios of mono-O-sulphated/di-O-sulphated (N-sulphated) disaccharide units, and in addition, with relatively large amounts of 2-sulphated L-iduronic acid residues bound to C-4 of N-sulpho-D-glucosamine units lacking O-sulphate substituents.", "contents": "Identification of N-sulphated disaccharide units in heparin-like polysaccharides. 1. Preparations of heparin and heparan sulphate were degraded with HNO2. The resulting disaccharides were isolated by gel chromatography, reduced with either NaBH4 or NaB3H4 and were then fractionated into non-sulphated, monosulphated and disulphated species by ion-exchange chromatography or by paper electrophoresis. The non-sulphated disaccharides were separated into two, and the monosulphated disaccharides into three, components by paper chromatography. 2. The uronic acid moieties of the various non- and mono-sulphated disaccharides were identified by means of radioactive labels selectively introduced into uronic acid residues (3H and 14C in D-glucuronic acid, 14C only in L-iduronic acid units) during biosynthesis of the polysaccharide starting material. Labelled uronic acids were also identified by paper chromatography, after liberation from disaccharides by acid hydrolysis or by glucuronidase digestion. Similar procedures, applied to disaccharides treated with NaB3H4, indicated 2,5-anhydro-D-mannitol as reducing terminal unit. On the basis of these results, and the known positions and configurations of the glycosidic linkages in heparin, the two non-sulphated disaccharides were identified as 4-O-(beta-D-glucopyranosyluronic acid)-2,5-anhydro-D-mannitol and 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol. 3. The three monosulphated [1-3H]anhydromannitol-labelled disaccharides were subjected to Smith degradation or to digestion with homogenates of human skin fibroblasts, and the products were analysed by paper electrophoresis. The results, along with the 1H n.m.r. spectra of the corresponding unlabelled disaccharides, permitted the allocation of O-sulphate groups to various positions in the disaccharides. These were thus identified as 4-O-(beta-D-glucopyranosyl-uronic acid)-2,5-anhydro-D-mannitol 6-sulphate, 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol 6-sulphate and 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol. The last-mentioned disaccharide was found to be a poor substrate for the iduronate sulphatase of human skin fibroblasts, as compared with the disulphated species, 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol 6-sulphate. 4. The identified [1-3H]anhydromannitol-labelled disaccharides were used as reference standards in a study of the disaccharide composition of heparins and heparan sulphates. Low N-sulphate contents, most pronounced in the heparin sulphates, were associated with high ratios of mono-O-sulphated/di-O-sulphated (N-sulphated) disaccharide units, and in addition, with relatively large amounts of 2-sulphated L-iduronic acid residues bound to C-4 of N-sulpho-D-glucosamine units lacking O-sulphate substituents."} {"id": "PMID:157741", "title": "The effect of amphiphilic phenylalkyl derivatives on platelet energy metabolism. Stimulation of glycolysis through activation of membrane ATPase.", "content": "In order to obtain information about the target of membrane-active inhibitors of platelet aggregation two phenylalkanoles and two phenylalkylamines were examined with respect to their influence on membrane ATPase and energy metabolism. The phenylalkanoles, 2-phenylethanol and 3-phenylpropanol, strongly enhanced the liberation in washed platelets of inorganic phosphate (Pi) from endogenous substrate or added ATP. A simultaneous decrease was found in the ATP/ADP ratio while glucose uptake, glycogen utilization and lactate formation increased. The effects of 2-phenylethanol and 3-phenylpropanol on Pi liberation and ATP/ADP ratio were detectable only with starving platelets; the stimulation of glycolysis could also be seen when glucose was added. It is concluded that presence of glucose enabled the platelets to reincorporate additionally liberated Pi into their ATP pool by virtue of the higher metabolic rate. The data suggest that a membrane-ATPase, possibly thrombosthenin ATPase, is the target of the phenylalkanoles. The phenylalkylamines, 2-phenylethylamine and 4-phenylbutylamine, appeared to inhibit Pi liberation and energy metabolism. Hence the aggregation inhibition produced by amphiphilic phenylalkylamines and phenylalkanoles is not due to a uniform metabolic effect of both classes of derivatives.", "contents": "The effect of amphiphilic phenylalkyl derivatives on platelet energy metabolism. Stimulation of glycolysis through activation of membrane ATPase. In order to obtain information about the target of membrane-active inhibitors of platelet aggregation two phenylalkanoles and two phenylalkylamines were examined with respect to their influence on membrane ATPase and energy metabolism. The phenylalkanoles, 2-phenylethanol and 3-phenylpropanol, strongly enhanced the liberation in washed platelets of inorganic phosphate (Pi) from endogenous substrate or added ATP. A simultaneous decrease was found in the ATP/ADP ratio while glucose uptake, glycogen utilization and lactate formation increased. The effects of 2-phenylethanol and 3-phenylpropanol on Pi liberation and ATP/ADP ratio were detectable only with starving platelets; the stimulation of glycolysis could also be seen when glucose was added. It is concluded that presence of glucose enabled the platelets to reincorporate additionally liberated Pi into their ATP pool by virtue of the higher metabolic rate. The data suggest that a membrane-ATPase, possibly thrombosthenin ATPase, is the target of the phenylalkanoles. The phenylalkylamines, 2-phenylethylamine and 4-phenylbutylamine, appeared to inhibit Pi liberation and energy metabolism. Hence the aggregation inhibition produced by amphiphilic phenylalkylamines and phenylalkanoles is not due to a uniform metabolic effect of both classes of derivatives."} {"id": "PMID:157769", "title": "Interaction of halothane with non-depolarizing neuromuscular blocking drugs in man.", "content": "1 Tetanic and single twitch contractions of the adductor pollicis muscles, in response to indirect stimulation of each ulnar nerve, were recorded in patients anaesthetized with thiopentone and nitrous oxide in oxygen. 2 Concentrations of 1 and 2% halothane were administered for 10 min during recovery from neuromuscular paralysis by tubocurarine, dimethyl tubocurarine and gallamine. 3 During exposure to halothane, the peak contraction of the tetanic response was reduced and tetanic fade was increased whereas the single twitch was unaffected. 4 The effects of halothane on the tetanic responses were readily antagonized by intravenous neostigmine preceded by atropine. 5 Halothane could act post-synaptically by a non-depolarizing block or by desensitizing the post-synaptic receptors, but a pre-synaptic action seems more likely since neuromuscular block was only evident when tetanic stimulation was applied. Such an effect could be caused by impairment of the release of acetylcholine.", "contents": "Interaction of halothane with non-depolarizing neuromuscular blocking drugs in man. 1 Tetanic and single twitch contractions of the adductor pollicis muscles, in response to indirect stimulation of each ulnar nerve, were recorded in patients anaesthetized with thiopentone and nitrous oxide in oxygen. 2 Concentrations of 1 and 2% halothane were administered for 10 min during recovery from neuromuscular paralysis by tubocurarine, dimethyl tubocurarine and gallamine. 3 During exposure to halothane, the peak contraction of the tetanic response was reduced and tetanic fade was increased whereas the single twitch was unaffected. 4 The effects of halothane on the tetanic responses were readily antagonized by intravenous neostigmine preceded by atropine. 5 Halothane could act post-synaptically by a non-depolarizing block or by desensitizing the post-synaptic receptors, but a pre-synaptic action seems more likely since neuromuscular block was only evident when tetanic stimulation was applied. Such an effect could be caused by impairment of the release of acetylcholine."} {"id": "PMID:157770", "title": "Suppressive effect of ferritin on in vitro lymphocyte function.", "content": "This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H-thymidine (3H-TdR). Ferritin (0.25--5.0 micrograms/ml culture) caused a marked suppression of PHA nad Con A blastogenesis but had no suppressive effect on PWM-induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 microgram/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K-562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T-lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T-cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.", "contents": "Suppressive effect of ferritin on in vitro lymphocyte function. This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H-thymidine (3H-TdR). Ferritin (0.25--5.0 micrograms/ml culture) caused a marked suppression of PHA nad Con A blastogenesis but had no suppressive effect on PWM-induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 microgram/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K-562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T-lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T-cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown."} {"id": "PMID:157771", "title": "Reduced number of peripheral blood granulocytic progenitor cells in patients with Down's syndrome.", "content": "The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.", "contents": "Reduced number of peripheral blood granulocytic progenitor cells in patients with Down's syndrome. The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed."} {"id": "PMID:157774", "title": "Purification of the energy-transducing adenosine triphosphatase complex from Rhodospirillum rubrum.", "content": "The oligomycin- and N,N'-dicyclohexylcarbodiimide-sensitive adenosine triphosphatase complex extracted with Triton X-100 from the chromatophores of Rhodospirillum rubrum was extensively purified. The purification procedure included (diethylamino)ethylcellulose chromatography and glycerol gradient centrifugation. The specific activity of Mg2+-dependent ATP hydrolysis in the purified preparation increased about 11-fold, while that of Ca2+-dependent ATP hydrolysis increased 50-fold as compared with chromatophores. The purified adenosine triphosphatase complex dissociated into a maximum of eight different polypeptides upon electrophoresis in the presence of sodium dodecyl sulfate. The estimated subunit molecular weights were as follows: 56 000 (alpha), 50 000 (beta), 33 000 (gamma), and those ranging from 17 000 to 9400 for the remaining smaller subunits. The purified preparation was incorporated into phospholipid vesicles by using the freeze--thaw technique. The reconstituted vesicles catalyzed [32P]ATP exchange, which was almost completely inhibited by both oligomycin and N,N'-dicyclohexylcarbodiimide as well as by a protonophorous uncoupler, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone.", "contents": "Purification of the energy-transducing adenosine triphosphatase complex from Rhodospirillum rubrum. The oligomycin- and N,N'-dicyclohexylcarbodiimide-sensitive adenosine triphosphatase complex extracted with Triton X-100 from the chromatophores of Rhodospirillum rubrum was extensively purified. The purification procedure included (diethylamino)ethylcellulose chromatography and glycerol gradient centrifugation. The specific activity of Mg2+-dependent ATP hydrolysis in the purified preparation increased about 11-fold, while that of Ca2+-dependent ATP hydrolysis increased 50-fold as compared with chromatophores. The purified adenosine triphosphatase complex dissociated into a maximum of eight different polypeptides upon electrophoresis in the presence of sodium dodecyl sulfate. The estimated subunit molecular weights were as follows: 56 000 (alpha), 50 000 (beta), 33 000 (gamma), and those ranging from 17 000 to 9400 for the remaining smaller subunits. The purified preparation was incorporated into phospholipid vesicles by using the freeze--thaw technique. The reconstituted vesicles catalyzed [32P]ATP exchange, which was almost completely inhibited by both oligomycin and N,N'-dicyclohexylcarbodiimide as well as by a protonophorous uncoupler, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone."} {"id": "PMID:157779", "title": "Proteochondroitin sulfate synthesized in cartilages induced in vivo and in vitro by bone matrix gelatin.", "content": "Implanted allogeneic demineralized bone matrix gelatin induced sequential development of cartilage and bone in the recipient rat muscle tissue. Proteoglycans of the implants labeled in vivo with [35S]sulfate at different stages of development were analyzed by sucrose density gradient centrifugation. The major proteoglycan synthesized in day-5 implant, just prior to onset of chondrogenesis, was a dermatan sulfate-containing proteoglycan with relatively slow sedimentation rate. Additionally, a small amount of a faster sedimenting component could be detected. The faster sedimenting proteoglycan, in which chondroitin 4-sulfate accounted for 85% of total radioactivity, became predominant in day-10 sample when cartilage formation was maximal. By day 30, when cartilage had been replaced by newly formed bone, the synthesis of this faster sedimenting component had ceased. A similar, if not identical, proteoglycan was found to be a major one synthesized by the in vitro-induced cartilage. This proteoglycan was smaller in overall size and shorter in length of its chondroitin sulfate chains than a major proteoglycan component obtained from neonatal rat epiphyseal cartilage. Concurrent with these changes in proteoglycan type, there appeared to be a change in collagen type, since type II collagen, in addition to type I collagen, was synthesized in day-10 implant. These results indicate that the proteoglycan can be used as a molecular marker for chondrogenesis by bone matrix gelatin.", "contents": "Proteochondroitin sulfate synthesized in cartilages induced in vivo and in vitro by bone matrix gelatin. Implanted allogeneic demineralized bone matrix gelatin induced sequential development of cartilage and bone in the recipient rat muscle tissue. Proteoglycans of the implants labeled in vivo with [35S]sulfate at different stages of development were analyzed by sucrose density gradient centrifugation. The major proteoglycan synthesized in day-5 implant, just prior to onset of chondrogenesis, was a dermatan sulfate-containing proteoglycan with relatively slow sedimentation rate. Additionally, a small amount of a faster sedimenting component could be detected. The faster sedimenting proteoglycan, in which chondroitin 4-sulfate accounted for 85% of total radioactivity, became predominant in day-10 sample when cartilage formation was maximal. By day 30, when cartilage had been replaced by newly formed bone, the synthesis of this faster sedimenting component had ceased. A similar, if not identical, proteoglycan was found to be a major one synthesized by the in vitro-induced cartilage. This proteoglycan was smaller in overall size and shorter in length of its chondroitin sulfate chains than a major proteoglycan component obtained from neonatal rat epiphyseal cartilage. Concurrent with these changes in proteoglycan type, there appeared to be a change in collagen type, since type II collagen, in addition to type I collagen, was synthesized in day-10 implant. These results indicate that the proteoglycan can be used as a molecular marker for chondrogenesis by bone matrix gelatin."} {"id": "PMID:157780", "title": "Selective exposure of mucopolysaccharides is involved in macrophage physiology.", "content": "Surface and intracellular mucopolysaccharides of guinea-pig peritoneal macrophages maintained in suspension and monolayer culture were studied. At least five classes of compound (hyaluronic acid, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate and chondroitin 6-sulfate) were resolved and characterized by electrophoresis and enzymatic degradation. The results reported here suggest that modulation of mucopolysaccharide exposure is involved in macrophage physiology. The possible biological role of surface mucopolysaccharides in macrophage activity is discussed.", "contents": "Selective exposure of mucopolysaccharides is involved in macrophage physiology. Surface and intracellular mucopolysaccharides of guinea-pig peritoneal macrophages maintained in suspension and monolayer culture were studied. At least five classes of compound (hyaluronic acid, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate and chondroitin 6-sulfate) were resolved and characterized by electrophoresis and enzymatic degradation. The results reported here suggest that modulation of mucopolysaccharide exposure is involved in macrophage physiology. The possible biological role of surface mucopolysaccharides in macrophage activity is discussed."} {"id": "PMID:157783", "title": "The effectiveness of EMG biofeedback training in low back pain.", "content": "Eighteen patients with chronic low back pain (lbp) of muscle tension origin were given an EMG biofeedback training. Compared to seven controls they showed a significant decrease during training in muscle tension and subsequently in pain. However, at follow-up EMG levels dropped to the initial (high) level. Pain scores of patients with high pain decrements during training showed further improvement during follow-up, which was not the case with patients showing less substantial improvement. The importance of cognitions was discussed.", "contents": "The effectiveness of EMG biofeedback training in low back pain. Eighteen patients with chronic low back pain (lbp) of muscle tension origin were given an EMG biofeedback training. Compared to seven controls they showed a significant decrease during training in muscle tension and subsequently in pain. However, at follow-up EMG levels dropped to the initial (high) level. Pain scores of patients with high pain decrements during training showed further improvement during follow-up, which was not the case with patients showing less substantial improvement. The importance of cognitions was discussed."} {"id": "PMID:157785", "title": "Temporal variations in androgens and stress hormones in control and schizophrenic subjects.", "content": "Radioimmunoassay methods were employed to study the steroid hormones dehydroepiandrosterone (DHEA), cortisol, testosterone, and androstenedione in schizophrenic and control subjects. Observations were made at four different times during the day. Cortisol, testosterone, and androstenedione demonstrated no significant differences between the two subjects groups. DHEA was significantly below normal in the morning for the schizophrenic group, but within the range of the controls for subsequent determinations during the day. Control subjects show a similar circadian secretion pattern for both DHEA and cortisol. Schizophrenics show almost the same circadian secretion patterns for cortisol as do the controls.", "contents": "Temporal variations in androgens and stress hormones in control and schizophrenic subjects. Radioimmunoassay methods were employed to study the steroid hormones dehydroepiandrosterone (DHEA), cortisol, testosterone, and androstenedione in schizophrenic and control subjects. Observations were made at four different times during the day. Cortisol, testosterone, and androstenedione demonstrated no significant differences between the two subjects groups. DHEA was significantly below normal in the morning for the schizophrenic group, but within the range of the controls for subsequent determinations during the day. Control subjects show a similar circadian secretion pattern for both DHEA and cortisol. Schizophrenics show almost the same circadian secretion patterns for cortisol as do the controls."} {"id": "PMID:157786", "title": "T lymphocytes in patients with Down's syndrome.", "content": "Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of \"avid\" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients.", "contents": "T lymphocytes in patients with Down's syndrome. Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of \"avid\" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients."} {"id": "PMID:157782", "title": "[Temperature-dependent functional changes in sarcoplasmic reticulum membranes].", "content": "Temperature effect on changes in calcium ion transport and activity of Ca-ATPase of sarcoplasmic reticulum vesicles (SRV) was studied. Several temperature intervals of the change of SRV functional activity parameters were found: 8-12 degrees C-beginning of accumulation of SRV Ca2+, 12-19 degrees sharp activation of Ca2+ accumulation, 27-32 degrees-activation of passive yield, 36-43 degrees-reversible change of the activity of the accumulation system and activation of Ca yield, 48 degrees and higher--irreversible denaturation of transport Ca-ATPase. Coincidence of temperature intervals of SRV structural reconstructions, detected by means of fluorescent probes and functional changes points to a close relationship between structural reconstructions and functional responses of biological membranes.", "contents": "[Temperature-dependent functional changes in sarcoplasmic reticulum membranes]. Temperature effect on changes in calcium ion transport and activity of Ca-ATPase of sarcoplasmic reticulum vesicles (SRV) was studied. Several temperature intervals of the change of SRV functional activity parameters were found: 8-12 degrees C-beginning of accumulation of SRV Ca2+, 12-19 degrees sharp activation of Ca2+ accumulation, 27-32 degrees-activation of passive yield, 36-43 degrees-reversible change of the activity of the accumulation system and activation of Ca yield, 48 degrees and higher--irreversible denaturation of transport Ca-ATPase. Coincidence of temperature intervals of SRV structural reconstructions, detected by means of fluorescent probes and functional changes points to a close relationship between structural reconstructions and functional responses of biological membranes."} {"id": "PMID:157787", "title": "Granulocytic chalone inhibits rapidly proliferating committed murine progenitor cells (CFU-C).", "content": "Bovine leucocyte extract containing the granulocytic chalone inhibited proliferation of rapidly, but not slowly, prliferating murine CFU-C. The precursors of CFU-C, i.e. multipotent colon-forming stem cells (CFU-S), were apparently not affected. Inhibition of proliferation was detected as a decreased killing of DNA synthesizing cells in diffusion chamber cultures by hydroxyurea, after pre-treatment with the extract.", "contents": "Granulocytic chalone inhibits rapidly proliferating committed murine progenitor cells (CFU-C). Bovine leucocyte extract containing the granulocytic chalone inhibited proliferation of rapidly, but not slowly, prliferating murine CFU-C. The precursors of CFU-C, i.e. multipotent colon-forming stem cells (CFU-S), were apparently not affected. Inhibition of proliferation was detected as a decreased killing of DNA synthesizing cells in diffusion chamber cultures by hydroxyurea, after pre-treatment with the extract."} {"id": "PMID:157784", "title": "A new type of organization of the genetic material in eukaryotes.", "content": "An investigation of the properties of a number of genes of Drosophila, obtained by cloning recombinant DNAs, led to the detection of a new type of organization of genetic material. It was found that a number of actively working structural genes of Drosophila are represented by a large number of copies, scattered over its chromosomes. Their localization in the chromosomes is variable, although they are always detected in regions of intercalary heterochromatin. The latter evidently is a site of accumulation of various multiple genes.", "contents": "A new type of organization of the genetic material in eukaryotes. An investigation of the properties of a number of genes of Drosophila, obtained by cloning recombinant DNAs, led to the detection of a new type of organization of genetic material. It was found that a number of actively working structural genes of Drosophila are represented by a large number of copies, scattered over its chromosomes. Their localization in the chromosomes is variable, although they are always detected in regions of intercalary heterochromatin. The latter evidently is a site of accumulation of various multiple genes."} {"id": "PMID:157789", "title": "[Further purification of a tissue specific inhibitor in lymphopoiesis (lymphocyte chalone?) (author's transl)].", "content": "A partially purified calf spleen extract, which exhibits the properties of a lymphocyte chalone (tissue-specific, species non-specific, non-toxic and reversible acting, endogenous inhibitor of cell proliferation) as concerning biological activities, has been described earlier. This fraction has been further purified by ion exchange chromatography with DEAE-Sephacel to a 10,000-fold purification. The most active fraction inhibited 3H-thymidine incorporation into phytohemagglutinin- or pokeweed-mitogen-stimulated lymphocytes by 86% resp. 70%, when given in a concentration of 100 ng/ml. Ehrlich-ascites-cells were not inhibited by the same concentration. The inhibiting activity is compared to other published lymphocyte inhibitors.", "contents": "[Further purification of a tissue specific inhibitor in lymphopoiesis (lymphocyte chalone?) (author's transl)]. A partially purified calf spleen extract, which exhibits the properties of a lymphocyte chalone (tissue-specific, species non-specific, non-toxic and reversible acting, endogenous inhibitor of cell proliferation) as concerning biological activities, has been described earlier. This fraction has been further purified by ion exchange chromatography with DEAE-Sephacel to a 10,000-fold purification. The most active fraction inhibited 3H-thymidine incorporation into phytohemagglutinin- or pokeweed-mitogen-stimulated lymphocytes by 86% resp. 70%, when given in a concentration of 100 ng/ml. Ehrlich-ascites-cells were not inhibited by the same concentration. The inhibiting activity is compared to other published lymphocyte inhibitors."} {"id": "PMID:157791", "title": "Pseudocholinesterase activity and phenotypes in mentally ill patients.", "content": "Pseudocholinesterase activities and phenotypes have been determined in 103 affectively ill patients, 168 schizophrenics and 73 Huntington's disease sufferers and compared with those of a sample of healthy controls. The distributions of phenotypes in the patient samples did not differ significantly from those of the controls. When corrections were made for sex, age and E1 phenotypes, the Huntington's disease patients showed a reduced level of cholinesterase activity. Normal levels were found in affective disorders and schizophrenia.", "contents": "Pseudocholinesterase activity and phenotypes in mentally ill patients. Pseudocholinesterase activities and phenotypes have been determined in 103 affectively ill patients, 168 schizophrenics and 73 Huntington's disease sufferers and compared with those of a sample of healthy controls. The distributions of phenotypes in the patient samples did not differ significantly from those of the controls. When corrections were made for sex, age and E1 phenotypes, the Huntington's disease patients showed a reduced level of cholinesterase activity. Normal levels were found in affective disorders and schizophrenia."} {"id": "PMID:157792", "title": "Adenomatoid tumour of the epididymis: histochemical and ultrastructural study of 2 cases.", "content": "Two cases of adenomatoid tumour of the epididymis are described. Both the histochemical and ultrastructural studied support the concept that it is of mesothelial origin. The histochemical study showed the presence of acid mucopolysaccharides in the lumen of the tubular structures. The epithelial cells presented numerous microvilli in the free surface, junction complexes, wide intercellular channels and a well-developed Golgi complex. Abundant bundles of microfilaments and intracellular spaces were observed in the cytoplasm. Lymphocytes and histiocytes were identified both in the tubular lumen and between the epithelial cells. The stroma of the tumour was made up of dense connective tissue with abundant bundles of elastic fibres. The presence of intracytoplasmic spaces in the epithelial cells and elastic fibres in the stroma had not been previously observed in this tumour.", "contents": "Adenomatoid tumour of the epididymis: histochemical and ultrastructural study of 2 cases. Two cases of adenomatoid tumour of the epididymis are described. Both the histochemical and ultrastructural studied support the concept that it is of mesothelial origin. The histochemical study showed the presence of acid mucopolysaccharides in the lumen of the tubular structures. The epithelial cells presented numerous microvilli in the free surface, junction complexes, wide intercellular channels and a well-developed Golgi complex. Abundant bundles of microfilaments and intracellular spaces were observed in the cytoplasm. Lymphocytes and histiocytes were identified both in the tubular lumen and between the epithelial cells. The stroma of the tumour was made up of dense connective tissue with abundant bundles of elastic fibres. The presence of intracytoplasmic spaces in the epithelial cells and elastic fibres in the stroma had not been previously observed in this tumour."} {"id": "PMID:157793", "title": "Inhibition of reticuloendothelial function by gold and its relation to postinjection reactions.", "content": "A patient with rheumatoid arthritis developed severe exacerbation of symptoms 18 hours after an injection of gold thiomalate (sodium aurothiomalate). Immune complexes were present in his serum and synovial fluid; in the synovial fluid they were associated with intense complement activation. The effect of gold salts on splenic reticuloendothelial function was determined by measuring the clearance of heat-damaged erythrocytes from the circulation. Gold thiomalate (50 mg) substantially delayed clearance in the patient but had no effect in four other patients with rheumatoid arthritis who had not had a postinjection reaction. Severely impaired clearance also occurred in three out of four healthy people given 100 mg gold but they remained asymptomatic. The postinjection reaction may be an immune-complex disease that is triggered in certain patients because gold transiently inhibits reticuloendothelial function.", "contents": "Inhibition of reticuloendothelial function by gold and its relation to postinjection reactions. A patient with rheumatoid arthritis developed severe exacerbation of symptoms 18 hours after an injection of gold thiomalate (sodium aurothiomalate). Immune complexes were present in his serum and synovial fluid; in the synovial fluid they were associated with intense complement activation. The effect of gold salts on splenic reticuloendothelial function was determined by measuring the clearance of heat-damaged erythrocytes from the circulation. Gold thiomalate (50 mg) substantially delayed clearance in the patient but had no effect in four other patients with rheumatoid arthritis who had not had a postinjection reaction. Severely impaired clearance also occurred in three out of four healthy people given 100 mg gold but they remained asymptomatic. The postinjection reaction may be an immune-complex disease that is triggered in certain patients because gold transiently inhibits reticuloendothelial function."} {"id": "PMID:157796", "title": "The major intracellular alkaline deoxyribonuclease activities expressed in wild-type and Rec-like mutants of Neurospora crassa.", "content": "Over 95% of the deoxyribonuclease (DNase) activity of log-phase mycelia of Neurospora crassa is expressed as single-strand (ss) specific endonucleolytic activity. This activity is associated with three nucleases (D1, D2, and D3) which after partial purification from extracts, express activity with double-strand (ds) DNA as well. All three enzymes also degrade RNA at approximately the same rates that they degrade ss-DNA. D3 has been identified as endoexonuclease, an enzyme previously shown to have endonuclease activity with ss-DNA and RNA and exonuclease activity with ds-DNA, both of which are inhibited by ATP. D3 is inhibited by ATP, is relatively resistant to p-hydroxymercuribenzoate (PHMB), and sediments with an apparent molecular weight of 75 000. D2 has the properties of the previously described mitochondrial nuclease. It is a relatively unstable Mg2+-dependent endonuclease with no appreciable strand specificity for DNA. In addition, it is not inhibited by ATP and is strongly inhibited by PHMB and by the ethylenediamine tetraacetic acid (EDTA). It also sediments with an apparent molecular weight of 75,000. The properties of D1 are quite variable from one preparation to another. Freshly isolated D1 sediments with an apparent molecular weight of 180 000. It often shows some inhibition by ATP, but is relatively resistant to both PHMB and EDTA. However, on 'ageing,' the properties of D1 gradually convert to those of D2 with concomitant decrease in molecular weight, loss of inhibition by ATP, and increase in sensitivities to PHMB and EDTA. The results indicate that D1 is very likely a second form of the mitochondrial enzyme. Evidence was obtained for the presence of protein inhibitor(s) in crude extracts which may account for the masking of the ds-DNase activities of these enzymes in extracts. Two Rec-like mutants of Neurospora (uvs-3, and nuh-4) are deficient mainly inexpressed levels of D3, the endo-exonuclease. However, the levels of inactive endo-exonuclease precursor in these two mutants are higher than in the wild type. There may, therefore, be some defect in the conversion of precursor to active enzyme in these two mutants. Another mutant, which is not sensitive to mutagens relative to the wild (nuh-3), has depressed levels of both endo-exonuclease and the mitochondrial enzyme. Nuh-3 has some defect in the conversion of D1 to D2. Proteinases probably play some role in vivo in these enzyme conversions.", "contents": "The major intracellular alkaline deoxyribonuclease activities expressed in wild-type and Rec-like mutants of Neurospora crassa. Over 95% of the deoxyribonuclease (DNase) activity of log-phase mycelia of Neurospora crassa is expressed as single-strand (ss) specific endonucleolytic activity. This activity is associated with three nucleases (D1, D2, and D3) which after partial purification from extracts, express activity with double-strand (ds) DNA as well. All three enzymes also degrade RNA at approximately the same rates that they degrade ss-DNA. D3 has been identified as endoexonuclease, an enzyme previously shown to have endonuclease activity with ss-DNA and RNA and exonuclease activity with ds-DNA, both of which are inhibited by ATP. D3 is inhibited by ATP, is relatively resistant to p-hydroxymercuribenzoate (PHMB), and sediments with an apparent molecular weight of 75 000. D2 has the properties of the previously described mitochondrial nuclease. It is a relatively unstable Mg2+-dependent endonuclease with no appreciable strand specificity for DNA. In addition, it is not inhibited by ATP and is strongly inhibited by PHMB and by the ethylenediamine tetraacetic acid (EDTA). It also sediments with an apparent molecular weight of 75,000. The properties of D1 are quite variable from one preparation to another. Freshly isolated D1 sediments with an apparent molecular weight of 180 000. It often shows some inhibition by ATP, but is relatively resistant to both PHMB and EDTA. However, on 'ageing,' the properties of D1 gradually convert to those of D2 with concomitant decrease in molecular weight, loss of inhibition by ATP, and increase in sensitivities to PHMB and EDTA. The results indicate that D1 is very likely a second form of the mitochondrial enzyme. Evidence was obtained for the presence of protein inhibitor(s) in crude extracts which may account for the masking of the ds-DNase activities of these enzymes in extracts. Two Rec-like mutants of Neurospora (uvs-3, and nuh-4) are deficient mainly inexpressed levels of D3, the endo-exonuclease. However, the levels of inactive endo-exonuclease precursor in these two mutants are higher than in the wild type. There may, therefore, be some defect in the conversion of precursor to active enzyme in these two mutants. Another mutant, which is not sensitive to mutagens relative to the wild (nuh-3), has depressed levels of both endo-exonuclease and the mitochondrial enzyme. Nuh-3 has some defect in the conversion of D1 to D2. Proteinases probably play some role in vivo in these enzyme conversions."} {"id": "PMID:157797", "title": "Thymidine incorporation into Rhizobium meliloti.", "content": "Thymidine is rapidly catabolized to thymine, beta-aminoisobutyric acid, and carbon dioxide by Rhizobium meliloti cells. The incorporation of labelled thymidine into the DNA of R. meliloti cells can be enhanced by the addition of low concentrations (10-20 micrograms/mL) of deoxyadenosine or other nucleosides (adenosine, uridine, guanosine). However, at high concentrations ( greater than 50 micrograms/mL) these compounds inhibit thymidine incorporation. Conditions to obtain highly radioactive DNA of Rhizobium are described.", "contents": "Thymidine incorporation into Rhizobium meliloti. Thymidine is rapidly catabolized to thymine, beta-aminoisobutyric acid, and carbon dioxide by Rhizobium meliloti cells. The incorporation of labelled thymidine into the DNA of R. meliloti cells can be enhanced by the addition of low concentrations (10-20 micrograms/mL) of deoxyadenosine or other nucleosides (adenosine, uridine, guanosine). However, at high concentrations ( greater than 50 micrograms/mL) these compounds inhibit thymidine incorporation. Conditions to obtain highly radioactive DNA of Rhizobium are described."} {"id": "PMID:157798", "title": "Prolonged and continuous percutaneous intra-arterial hepatic infusion chemotherapy in advanced metastatic liver adenocarcinoma from colorectal primary.", "content": "Sixty patients with advanced metastatic adenocarcinoma of the liver from a colorectal primary were treated by prolonged and continuous intra-arterial hepatic arterial infusion chemotherapy over a period of time from December 1969 through July 1976. A 10-day course of 5-FU was administered in the hospital, and patients were discharged receiving 5-FUDR by continuous arterial infusion through a chronometric infusion pump. Objective responses of 100% were obtained in 15% of patients, 50% response in 39% of patients, and 25% response in 21% of patients. The median survival from onset of treatment was 8.5 months, 6.9 months, and 7 months, respectively, for 100%, 50%, and 25% responders versus 3.6 months for nonresponders. Survivals from onset of treatment were generally less in those with no disease-free interval. No relationship of response to sex and age was found. Patients previously treated with 5-FU intravenously responded to intra-arterial chemotherapy; 13% had a 100% response, and 54% had a 50% response. No relationship of drug dose to response was observed. Drug toxicity was frequently systemic and mild to moderate. Numerous complications occurred due to the catheter, complete or partial thrombosis occurring in 18.6% and 20.8%, respectively, and 30% of patients had displacement of the catheter. The role of partial arterial occlusion in terms of response and survival may be significant. Future studies should involve comparison of direct surgical placement versus percutaneous placement of catheters.", "contents": "Prolonged and continuous percutaneous intra-arterial hepatic infusion chemotherapy in advanced metastatic liver adenocarcinoma from colorectal primary. Sixty patients with advanced metastatic adenocarcinoma of the liver from a colorectal primary were treated by prolonged and continuous intra-arterial hepatic arterial infusion chemotherapy over a period of time from December 1969 through July 1976. A 10-day course of 5-FU was administered in the hospital, and patients were discharged receiving 5-FUDR by continuous arterial infusion through a chronometric infusion pump. Objective responses of 100% were obtained in 15% of patients, 50% response in 39% of patients, and 25% response in 21% of patients. The median survival from onset of treatment was 8.5 months, 6.9 months, and 7 months, respectively, for 100%, 50%, and 25% responders versus 3.6 months for nonresponders. Survivals from onset of treatment were generally less in those with no disease-free interval. No relationship of response to sex and age was found. Patients previously treated with 5-FU intravenously responded to intra-arterial chemotherapy; 13% had a 100% response, and 54% had a 50% response. No relationship of drug dose to response was observed. Drug toxicity was frequently systemic and mild to moderate. Numerous complications occurred due to the catheter, complete or partial thrombosis occurring in 18.6% and 20.8%, respectively, and 30% of patients had displacement of the catheter. The role of partial arterial occlusion in terms of response and survival may be significant. Future studies should involve comparison of direct surgical placement versus percutaneous placement of catheters."} {"id": "PMID:157799", "title": "Experimental squamous cell lung tumors in Sprague-Dawley and murine pneumonitis-free rats.", "content": "Squamous cell bronchogenic carcinoma was produced in 34% of a group of specific pathogen-free rats in a mean time of 139 days by the use of point-source irradiation. In a group of Sprague-Dawley rats, identical tumors developed in 54% of animals after an average exposure time of 147 days. This study was undertaken to clarify whether the bronchogenic squamous cell carcinomas produced by this method are due to the effects of the point source of irradiation alone or to the additive effects of irradiation and chronic murine pneumonitis. The results of this study in specific pathogen-free rats indicate that murine pneumonitis is not a prerequisite for the development of neoplasia by this method. The electron microscopic findings presented support the histologic diagnosis of a well-differentiated squamous cell bronchogenic carcinoma, similar in appearance to the tumor found in humans.", "contents": "Experimental squamous cell lung tumors in Sprague-Dawley and murine pneumonitis-free rats. Squamous cell bronchogenic carcinoma was produced in 34% of a group of specific pathogen-free rats in a mean time of 139 days by the use of point-source irradiation. In a group of Sprague-Dawley rats, identical tumors developed in 54% of animals after an average exposure time of 147 days. This study was undertaken to clarify whether the bronchogenic squamous cell carcinomas produced by this method are due to the effects of the point source of irradiation alone or to the additive effects of irradiation and chronic murine pneumonitis. The results of this study in specific pathogen-free rats indicate that murine pneumonitis is not a prerequisite for the development of neoplasia by this method. The electron microscopic findings presented support the histologic diagnosis of a well-differentiated squamous cell bronchogenic carcinoma, similar in appearance to the tumor found in humans."} {"id": "PMID:157801", "title": "Phase I trial of N-(phosphonacetyl)-L-aspartate.", "content": "A Phase I clinical trial of N-(phosphonacetyl)-L-aspartate, an antimetabolite which inhibits a key enzyme in the de novo pathway of pyrimidine biosynthesis, was conducted. N-(Phosphonacetyl)-L-aspartate was given as an i.v. 15-min infusion once daily for five days; cycles of treatment were repeated every three weeks. Thirty-four patients received treatment. Dose-limiting toxicity was observed at 1500 to 2000 mg/sq m/day and was manifested by skin rash, diarrhea, and stomatitis. Rash and diarrhea usually began during the first week of treatment and persisted up to Day 17 of a cycle of therapy. No consistent hematopoietic, hepatic, or renal toxicity was observed. One partial response in a patient with colon carcinoma was seen and continues at more than eight months. Stable disease was observed in three patients with colon carcinoma, two patients with hypernephroma, one patient with pancreatic carcinoma, and one patient with melanoma. The predictability and reversibility of toxicity and the suggestion of antitumor activity in humans are observations which support the further evaluation of N-(phosphonacetyl)-L-aspartate in Phase II studies.", "contents": "Phase I trial of N-(phosphonacetyl)-L-aspartate. A Phase I clinical trial of N-(phosphonacetyl)-L-aspartate, an antimetabolite which inhibits a key enzyme in the de novo pathway of pyrimidine biosynthesis, was conducted. N-(Phosphonacetyl)-L-aspartate was given as an i.v. 15-min infusion once daily for five days; cycles of treatment were repeated every three weeks. Thirty-four patients received treatment. Dose-limiting toxicity was observed at 1500 to 2000 mg/sq m/day and was manifested by skin rash, diarrhea, and stomatitis. Rash and diarrhea usually began during the first week of treatment and persisted up to Day 17 of a cycle of therapy. No consistent hematopoietic, hepatic, or renal toxicity was observed. One partial response in a patient with colon carcinoma was seen and continues at more than eight months. Stable disease was observed in three patients with colon carcinoma, two patients with hypernephroma, one patient with pancreatic carcinoma, and one patient with melanoma. The predictability and reversibility of toxicity and the suggestion of antitumor activity in humans are observations which support the further evaluation of N-(phosphonacetyl)-L-aspartate in Phase II studies."} {"id": "PMID:157802", "title": "Interaction of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate with cells in mixed-lymphocyte culture.", "content": "12-O-Tetradecanoylphorbol-13-acetate (TPA) inhibits DNA synthesis in bovine lymph node lymphocytes in mixed-lymphocyte cultures. Using a radioautographic study, we determined that TPA also blocked morphological changes in these cultures. Pretreatment of cultures of isologous lymphocytes with 10(-7) M TPA for three days prior to mixing was sufficient to block their subsequent response in mixed culture. Thus, TPA did not need to be present during the initial cell-to-cell interactions of the mixed lymphocyte response. The inhibition was not due to the death of the responding cell population because the effect was reversible. In one-way mixed-lymphocyte cultures, TPA pretreatment of either responding or stimulating cells could block DNA synthesis. The responding cells were more sensitive to TPA than were the stimulating cells. The inhibitory effect of the stimulators increased with an increase in the stimulating-to-responding cell ratio. In one-way cultures, it was also seen that lymphocytes from different animals varied both in their sensitivity to TPA and in their response to TPA-treated cells from other animals. The data taken together are consistent with the idea that TPA acts by changing cell surface recognition structures and/or indirectly, through activation of a subpopulation of cells to block the proliferative response. TPA may prove to be a valuable tool in studying cell-cell interactions and lymphocyte differentiation in vitro.", "contents": "Interaction of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate with cells in mixed-lymphocyte culture. 12-O-Tetradecanoylphorbol-13-acetate (TPA) inhibits DNA synthesis in bovine lymph node lymphocytes in mixed-lymphocyte cultures. Using a radioautographic study, we determined that TPA also blocked morphological changes in these cultures. Pretreatment of cultures of isologous lymphocytes with 10(-7) M TPA for three days prior to mixing was sufficient to block their subsequent response in mixed culture. Thus, TPA did not need to be present during the initial cell-to-cell interactions of the mixed lymphocyte response. The inhibition was not due to the death of the responding cell population because the effect was reversible. In one-way mixed-lymphocyte cultures, TPA pretreatment of either responding or stimulating cells could block DNA synthesis. The responding cells were more sensitive to TPA than were the stimulating cells. The inhibitory effect of the stimulators increased with an increase in the stimulating-to-responding cell ratio. In one-way cultures, it was also seen that lymphocytes from different animals varied both in their sensitivity to TPA and in their response to TPA-treated cells from other animals. The data taken together are consistent with the idea that TPA acts by changing cell surface recognition structures and/or indirectly, through activation of a subpopulation of cells to block the proliferative response. TPA may prove to be a valuable tool in studying cell-cell interactions and lymphocyte differentiation in vitro."} {"id": "PMID:157803", "title": "Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome.", "content": "Cells from patients with the hereditary disorder Cockayne's syndrome and from the sun-sensitive individual, 11961, are sensitive to the lethal effects of ultraviolet light (UV) but have no detectable defect in either excision- or postreplication repair after UV irradiation. In normal cells and in Cockayne heterozygotes, UV causes a depression in the rate of DNA-replicative synthesis followed by a recovery of normal rates 5 to 8 hr after irradiation. In Cockayne and 11961 cells, the initial depression in DNA synthesis is the same as that in normal cells, but no subsequent recovery is observed. The recovery of DNA synthesis in normal cells appears to be unaffected by fluorodeoxyuridine but inhibited by cycloheximide. This suggests a possible requirement for de novo protein synthesis, but there are a number of alternative interpretations of these data.", "contents": "Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome. Cells from patients with the hereditary disorder Cockayne's syndrome and from the sun-sensitive individual, 11961, are sensitive to the lethal effects of ultraviolet light (UV) but have no detectable defect in either excision- or postreplication repair after UV irradiation. In normal cells and in Cockayne heterozygotes, UV causes a depression in the rate of DNA-replicative synthesis followed by a recovery of normal rates 5 to 8 hr after irradiation. In Cockayne and 11961 cells, the initial depression in DNA synthesis is the same as that in normal cells, but no subsequent recovery is observed. The recovery of DNA synthesis in normal cells appears to be unaffected by fluorodeoxyuridine but inhibited by cycloheximide. This suggests a possible requirement for de novo protein synthesis, but there are a number of alternative interpretations of these data."} {"id": "PMID:157804", "title": "Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action.", "content": "The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.", "contents": "Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action. The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated."} {"id": "PMID:157805", "title": "Assay of intracellular free and macromolecular-bound metabolites of 5-fluorodeoxyuridine and 5-fluorouracil.", "content": "Methods have been developed to assay several aspects of 5-fluoro-2'-deoxyuridine and 5-fluorouracil metabolism in tissue culture cells. These methods allow measurement of (a) intracellular levels of the covalent complex formed between 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), 5,10-methylenetetrahydrofolate, and thymidylate synthetase; (b) incorporation of drug into RNA; and (c) analysis of drug metabolites. The methods were developed using radioactively labeled drugs, but they should be adaptable to studies using nonlabeled compounds. Sephadex G-25 chromatography or trichloroacetic acid precipitation were utilized for isolation of the macromolecular cell fraction; prior treatment of this fraction with RNase or heating at 65 degrees for 15 min resulted in selective removal of RNA or the thymidylate synthetase complex, respectively, from the precipitable fraction. Free intracellular drug metabolites present in the acid-soluble fraction were analyzed by high-pressure liquid chromatography. Following incubation of HTC cells with [6-3H]-5-fluoro-2'-deoxyuridine, a radioactive macromolecule was isolated and identified as a FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex. Intracellular formation of this complex was shown to be dependent on the presence of the enzyme thymidine kinase. Dissociation of the complex in vivo was first order with a t1/2 of 6.2 hr; in contrast, a t1/2 of 2 hr was determined for dissociation of the complex in cytosol. Incubation of L1210 cells with [6-3H]-5-fluorouracil for 22 hr resulted in formation of 80 fmol of FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex per 10(6) cells, as compared with 400 fmol of drug incorporated into RNA per 10(6) cells. Intracellular FdUMP could not be detected in the acid-soluble fraction of these cells unless the cells were first heated to dissociate the complex.", "contents": "Assay of intracellular free and macromolecular-bound metabolites of 5-fluorodeoxyuridine and 5-fluorouracil. Methods have been developed to assay several aspects of 5-fluoro-2'-deoxyuridine and 5-fluorouracil metabolism in tissue culture cells. These methods allow measurement of (a) intracellular levels of the covalent complex formed between 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), 5,10-methylenetetrahydrofolate, and thymidylate synthetase; (b) incorporation of drug into RNA; and (c) analysis of drug metabolites. The methods were developed using radioactively labeled drugs, but they should be adaptable to studies using nonlabeled compounds. Sephadex G-25 chromatography or trichloroacetic acid precipitation were utilized for isolation of the macromolecular cell fraction; prior treatment of this fraction with RNase or heating at 65 degrees for 15 min resulted in selective removal of RNA or the thymidylate synthetase complex, respectively, from the precipitable fraction. Free intracellular drug metabolites present in the acid-soluble fraction were analyzed by high-pressure liquid chromatography. Following incubation of HTC cells with [6-3H]-5-fluoro-2'-deoxyuridine, a radioactive macromolecule was isolated and identified as a FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex. Intracellular formation of this complex was shown to be dependent on the presence of the enzyme thymidine kinase. Dissociation of the complex in vivo was first order with a t1/2 of 6.2 hr; in contrast, a t1/2 of 2 hr was determined for dissociation of the complex in cytosol. Incubation of L1210 cells with [6-3H]-5-fluorouracil for 22 hr resulted in formation of 80 fmol of FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex per 10(6) cells, as compared with 400 fmol of drug incorporated into RNA per 10(6) cells. Intracellular FdUMP could not be detected in the acid-soluble fraction of these cells unless the cells were first heated to dissociate the complex."} {"id": "PMID:157806", "title": "Restoration of cyclophosphamide-induced suppression of thymus-derived cytotoxic cell generation by normal thymocytes.", "content": "Spleen cells from mice treated with cyclophosphamide (100 to 200 mg/kg) were unable to generate effective cytotoxic thymus-derived cells to allogeneic tumor cells in vitro. The inability of lymphoid cells from cyclophosphamide-treated mice to generate thymus-derived cytotoxic cells became more apparent as the number of responding cells became limited. This depressed response was not due to the elimination of cytotoxic precursor cells since normal response levels were restored by the addition of thymus cells. The added thymus cells did not provide cytotoxic cells in the culture. The thymus cells active in restoring cytotoxic activity were sensitive to mitomycin C, cyclophosphamide, and anti-theta serum and complement. In addition, the active thymus cells were located in the cortisone-resistant pool and did not adhere to nylon wool columns.", "contents": "Restoration of cyclophosphamide-induced suppression of thymus-derived cytotoxic cell generation by normal thymocytes. Spleen cells from mice treated with cyclophosphamide (100 to 200 mg/kg) were unable to generate effective cytotoxic thymus-derived cells to allogeneic tumor cells in vitro. The inability of lymphoid cells from cyclophosphamide-treated mice to generate thymus-derived cytotoxic cells became more apparent as the number of responding cells became limited. This depressed response was not due to the elimination of cytotoxic precursor cells since normal response levels were restored by the addition of thymus cells. The added thymus cells did not provide cytotoxic cells in the culture. The thymus cells active in restoring cytotoxic activity were sensitive to mitomycin C, cyclophosphamide, and anti-theta serum and complement. In addition, the active thymus cells were located in the cortisone-resistant pool and did not adhere to nylon wool columns."} {"id": "PMID:157807", "title": "Clinical trial of weekly pyrazofurin.", "content": "Pyrazofurin was administered to 21 patients with solid tumors at a dose of 200 mg/m2 iv weekly, because this dose had been shown to be well-tolerated and pharmacologic effects of a single dose at this level persisted for up to 7 days. An anemia consistent with a disturbance in rbc production was seen in most patients. Other toxic effects included stomatitis, rash, and myelosuppression. No complete or partial responses were noted, but two patients with alveolar cell carcinoma of the lung each had stable disease for 12 months. Most of the patients in this study tolerated the weekly dosage schedule well with only minimal myelosuppression, suggesting that this agent and schedule might be acceptable for use in combination chemotherapy. Several theoretic reasons favor the use of pyrazofurin in this manner. Pyrazofurin should also be evaluated more fully in patients with polycythemia vera, mycosis fungoides, and psoriasis, since other orotidylate decarboxylase inhibitors have been shown to be effective in these diseases.", "contents": "Clinical trial of weekly pyrazofurin. Pyrazofurin was administered to 21 patients with solid tumors at a dose of 200 mg/m2 iv weekly, because this dose had been shown to be well-tolerated and pharmacologic effects of a single dose at this level persisted for up to 7 days. An anemia consistent with a disturbance in rbc production was seen in most patients. Other toxic effects included stomatitis, rash, and myelosuppression. No complete or partial responses were noted, but two patients with alveolar cell carcinoma of the lung each had stable disease for 12 months. Most of the patients in this study tolerated the weekly dosage schedule well with only minimal myelosuppression, suggesting that this agent and schedule might be acceptable for use in combination chemotherapy. Several theoretic reasons favor the use of pyrazofurin in this manner. Pyrazofurin should also be evaluated more fully in patients with polycythemia vera, mycosis fungoides, and psoriasis, since other orotidylate decarboxylase inhibitors have been shown to be effective in these diseases."} {"id": "PMID:157808", "title": "Phase I study of 5-fluorodeoxyuridine plus cytosine arabinoside infusions in patients with solid tumors.", "content": "A phase I trial was conducted in 30 patients with solid tumors, using infusions of 5-fluorodeoxyuridine (5-FUdR) plus cytosine arabinoside (ara-C). Doses of 5-FUdR administered over 2 hours daily X 5 ranged from 0.02 to 1.0 mg/kg, and these doses immediately preceded a 1-hour infusion of ara-C. These schedules were selected because 5-FUdR pretreatment had been shown to sensitize L5178Y cells in culture to acute cell death by ara-C. Dose-limiting toxicity was myelosuppression. Based upon results in this study, the recommended dose of 5-FUdR to be used in phase II trials of this combination is 0.04--0.05 mg/kg (1.6--2.0 mg/m2) given prior to ara-C at a dose of 100 mg/m2. Antitumor responses were seen in patients with head and neck cancer, breast carcinoma, and carcinoid syndrome.", "contents": "Phase I study of 5-fluorodeoxyuridine plus cytosine arabinoside infusions in patients with solid tumors. A phase I trial was conducted in 30 patients with solid tumors, using infusions of 5-fluorodeoxyuridine (5-FUdR) plus cytosine arabinoside (ara-C). Doses of 5-FUdR administered over 2 hours daily X 5 ranged from 0.02 to 1.0 mg/kg, and these doses immediately preceded a 1-hour infusion of ara-C. These schedules were selected because 5-FUdR pretreatment had been shown to sensitize L5178Y cells in culture to acute cell death by ara-C. Dose-limiting toxicity was myelosuppression. Based upon results in this study, the recommended dose of 5-FUdR to be used in phase II trials of this combination is 0.04--0.05 mg/kg (1.6--2.0 mg/m2) given prior to ara-C at a dose of 100 mg/m2. Antitumor responses were seen in patients with head and neck cancer, breast carcinoma, and carcinoid syndrome."} {"id": "PMID:157809", "title": "Host resistance to tumor after cure of advanced LSA lymphoma by treatment with BCNU and chlorozotocin.", "content": "C57BL mice carrying the syngeneic advanced LSA ascites lymphoma initiated with a 10(6)-cell LSA inoculum were treated with four combinations of BCNU and/or chlorozotocin (CLZ) on Days 5 and 6 after tumor inoculation. The percentage of mice surviving greater than or equal to 60 days was greater than 80% for all four combinations. Surviving mice were then challenged with live LSA cells beginning with 100 cells and increasing the inoculum by factors of 10 every 3 weeks until a 10(7)-cell inoculum level was reached. The latter dose was repeated four times. A marked difference in resistance to tumor challenge was observed for the various groups. Surviving tumor-resistant mice at the end of the experiment, classified by original treatment, were as follows: BCNU-BCNU, 86.7%; CLZ-BCNU, 56.3%; BCNU-CLZ, 23.5% and CLZ-CLZ, 0. Various hypotheses are presented which might explain these differences.", "contents": "Host resistance to tumor after cure of advanced LSA lymphoma by treatment with BCNU and chlorozotocin. C57BL mice carrying the syngeneic advanced LSA ascites lymphoma initiated with a 10(6)-cell LSA inoculum were treated with four combinations of BCNU and/or chlorozotocin (CLZ) on Days 5 and 6 after tumor inoculation. The percentage of mice surviving greater than or equal to 60 days was greater than 80% for all four combinations. Surviving mice were then challenged with live LSA cells beginning with 100 cells and increasing the inoculum by factors of 10 every 3 weeks until a 10(7)-cell inoculum level was reached. The latter dose was repeated four times. A marked difference in resistance to tumor challenge was observed for the various groups. Surviving tumor-resistant mice at the end of the experiment, classified by original treatment, were as follows: BCNU-BCNU, 86.7%; CLZ-BCNU, 56.3%; BCNU-CLZ, 23.5% and CLZ-CLZ, 0. Various hypotheses are presented which might explain these differences."} {"id": "PMID:157810", "title": "Effect of intravenous glibornuride and tolbutamide on myocardial contractility.", "content": "The acute effects of therapeutic doses of intravenous tolbutamide and glibornuride on the systolic time intervals (QS2c, LVETc, PEPc and PEP/LVET) were examined in 5 healthy volunteers. Blood sugar was maintained constant throughout the study. No significant changes of these intervals as well as of heart rate and blood pressure were observed. Therefore, it is concluded that tolbutamide and glibornuride have no acute positive inotropic action.", "contents": "Effect of intravenous glibornuride and tolbutamide on myocardial contractility. The acute effects of therapeutic doses of intravenous tolbutamide and glibornuride on the systolic time intervals (QS2c, LVETc, PEPc and PEP/LVET) were examined in 5 healthy volunteers. Blood sugar was maintained constant throughout the study. No significant changes of these intervals as well as of heart rate and blood pressure were observed. Therefore, it is concluded that tolbutamide and glibornuride have no acute positive inotropic action."} {"id": "PMID:157812", "title": "Effects of adenine nucleotides on calcium binding by rat heart sarcoplasmic reticulum.", "content": "The purpose of the present study was to investigate the interactions between ATP, ADP and calcium binding by rat heart sarcoplasmic reticulum vesicles (SR), and to re-evaluate the assay method used to study calcium binding. Calcium binding or transport was studied by the Millipore filtration method. Rat heart SR has an unusually high Mg2+ stimulated ATPase activity (1.37 +/- 0.16 mumol Pi per min per mg at 25 degrees C) so that previous incubation with ATP in calcium binding studies releases ADP and Pi. By maintaining ATP at high and ADP at low concentrations with an ATP-regenerating system (phosphoenolpyruvate and pyruvate kinase), calcium binding capacity was increased by two to three times that of a non-ATP-regenerating system and there was a direct relationship between the amount of Ca-binding and SR protein concentration. When Ca2+ and Mg2+ concentrations were controlled and ATP and ADP concentrations were varied independently the initial rate of Ca-binding was inhibited 25% by 1 mmol.litre-1 ADP and 48% by 3mmol.litre-1 ADP. ATP limited the initial rate of Ca-binding only at ATP levels below 2mmol.litre-1. At low ATP concentrations Ca-release was observed. However, in the presence of an ATP-regenerating system no Ca-release was observed, even at low concentrations of ATP. This study shows that ADP is an inhibitor of Ca-binding by rat heart SR. However, the possibility that high ADP concentrations in the presence of Pi from ATP hydrolysis, could facilitate calcium release cannot be excluded. In addition to the possible physiological importance, these effects must be regarded when assaying rat cardiac SR calcium binding.", "contents": "Effects of adenine nucleotides on calcium binding by rat heart sarcoplasmic reticulum. The purpose of the present study was to investigate the interactions between ATP, ADP and calcium binding by rat heart sarcoplasmic reticulum vesicles (SR), and to re-evaluate the assay method used to study calcium binding. Calcium binding or transport was studied by the Millipore filtration method. Rat heart SR has an unusually high Mg2+ stimulated ATPase activity (1.37 +/- 0.16 mumol Pi per min per mg at 25 degrees C) so that previous incubation with ATP in calcium binding studies releases ADP and Pi. By maintaining ATP at high and ADP at low concentrations with an ATP-regenerating system (phosphoenolpyruvate and pyruvate kinase), calcium binding capacity was increased by two to three times that of a non-ATP-regenerating system and there was a direct relationship between the amount of Ca-binding and SR protein concentration. When Ca2+ and Mg2+ concentrations were controlled and ATP and ADP concentrations were varied independently the initial rate of Ca-binding was inhibited 25% by 1 mmol.litre-1 ADP and 48% by 3mmol.litre-1 ADP. ATP limited the initial rate of Ca-binding only at ATP levels below 2mmol.litre-1. At low ATP concentrations Ca-release was observed. However, in the presence of an ATP-regenerating system no Ca-release was observed, even at low concentrations of ATP. This study shows that ADP is an inhibitor of Ca-binding by rat heart SR. However, the possibility that high ADP concentrations in the presence of Pi from ATP hydrolysis, could facilitate calcium release cannot be excluded. In addition to the possible physiological importance, these effects must be regarded when assaying rat cardiac SR calcium binding."} {"id": "PMID:157815", "title": "Organization of tRNA and rRNA genes in N. crassa mitochondria: intervening sequence in the large rRNA gene and strand distribution of the RNA genes.", "content": "Through analysis of cloned fragments of N. crassa mitochondrial DNA, we have derived a physical map for the region of the mitochondrial genome which encodes the ribosomal RNAs and most of the tRNAs. We have located RNA genes on this map by hybridization of purified 32P end-labeled RNA probes, and our findings are as follows. First, the gene for the large ribosomal RNA contains an intervening sequence of approximately 2000 bp. Second, the genes for the small and large ribosomal RNAs are not adjacent, as previously reported, and the region between them contains a number of tRNA genes, including that for the mitochondrial tRNATyr, which is located close to the small rRNA gene on the same strand of the mitochondrial DNA. Third, there is a second cluster of tRNA genes on the mitochondrial DNA following the large ribosomal RNA gene, but there is no evidence for the presence of tRNA genes in the intervening sequence of the large ribosomal RNA. Fourth, hybridization of labeled ribosomal and transfer RNAs to the separated strands of a cloned 16 kbp DNA fragment covering this region indicates that the two ribosomal RNAs and most, if not all, of the mitochondrial tRNAs are encoded on one strand of the mitochondrial DNA.", "contents": "Organization of tRNA and rRNA genes in N. crassa mitochondria: intervening sequence in the large rRNA gene and strand distribution of the RNA genes. Through analysis of cloned fragments of N. crassa mitochondrial DNA, we have derived a physical map for the region of the mitochondrial genome which encodes the ribosomal RNAs and most of the tRNAs. We have located RNA genes on this map by hybridization of purified 32P end-labeled RNA probes, and our findings are as follows. First, the gene for the large ribosomal RNA contains an intervening sequence of approximately 2000 bp. Second, the genes for the small and large ribosomal RNAs are not adjacent, as previously reported, and the region between them contains a number of tRNA genes, including that for the mitochondrial tRNATyr, which is located close to the small rRNA gene on the same strand of the mitochondrial DNA. Third, there is a second cluster of tRNA genes on the mitochondrial DNA following the large ribosomal RNA gene, but there is no evidence for the presence of tRNA genes in the intervening sequence of the large ribosomal RNA. Fourth, hybridization of labeled ribosomal and transfer RNAs to the separated strands of a cloned 16 kbp DNA fragment covering this region indicates that the two ribosomal RNAs and most, if not all, of the mitochondrial tRNAs are encoded on one strand of the mitochondrial DNA."} {"id": "PMID:157820", "title": "Changes in mitochondrial DNA in cardiac hypertrophy in the rat.", "content": "We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of the mtDNA was assessed from its molecular conformation (open and closed circles) and by renaturation-kinetic analysis. The mtDNA concentration in mitochondria, expressed as micrograms of DNA per milligram of mitochondrial protein, increased 2, 4, and 7 days postoperatively by 21, 73, and 98%, respectively. Similar results were obtained when mtDNA was expressed per nonomole of cytochrome a. The population of replicative intermediates of mtDNA was analyzed by electron microscopy. In normal hearts, we observed molecular forms characteristic of animal mtDNA, such as circular monomers and dimers, catenated molecules, D-loops, expanded D-loops, and gapped molecules. D-loop frequency, which was near 50% in the mtDNA of control hearts, was markedly reduced to 5-7% in hypertrophying hearts. This result indicates that the increase in replicative flux of mtDNA is associated with the removal of a block in the conversion of D-loops to other intermediates.", "contents": "Changes in mitochondrial DNA in cardiac hypertrophy in the rat. We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of the mtDNA was assessed from its molecular conformation (open and closed circles) and by renaturation-kinetic analysis. The mtDNA concentration in mitochondria, expressed as micrograms of DNA per milligram of mitochondrial protein, increased 2, 4, and 7 days postoperatively by 21, 73, and 98%, respectively. Similar results were obtained when mtDNA was expressed per nonomole of cytochrome a. The population of replicative intermediates of mtDNA was analyzed by electron microscopy. In normal hearts, we observed molecular forms characteristic of animal mtDNA, such as circular monomers and dimers, catenated molecules, D-loops, expanded D-loops, and gapped molecules. D-loop frequency, which was near 50% in the mtDNA of control hearts, was markedly reduced to 5-7% in hypertrophying hearts. This result indicates that the increase in replicative flux of mtDNA is associated with the removal of a block in the conversion of D-loops to other intermediates."} {"id": "PMID:157821", "title": "Lack of effect of prolactin suppression on plasma dehydroepiandrosterone sulphate.", "content": "In twelve patients with hyperprolactinaemia, treatment which reduced plasma prolactin from a mean of 531 microgram/l (range 68-3500 microgram/1) to 8.3 microgram/l (0-27 microgram/l), caused no significant change in plasma dehydroepiandrosterone sulphate (DHA-SO4). Pre-treatment levels of DHA-SO4 were within the normal range in eleven out of twelve cases. The results do not support for claims that prolactin excess is associated with an increase in circulating DHA-SO4.", "contents": "Lack of effect of prolactin suppression on plasma dehydroepiandrosterone sulphate. In twelve patients with hyperprolactinaemia, treatment which reduced plasma prolactin from a mean of 531 microgram/l (range 68-3500 microgram/1) to 8.3 microgram/l (0-27 microgram/l), caused no significant change in plasma dehydroepiandrosterone sulphate (DHA-SO4). Pre-treatment levels of DHA-SO4 were within the normal range in eleven out of twelve cases. The results do not support for claims that prolactin excess is associated with an increase in circulating DHA-SO4."} {"id": "PMID:157822", "title": "Down's syndrome in Western Australia: mortality and survival.", "content": "An epidemiological investigation of 231 cases of Down's Syndrome born in Western Australia between 1966 and 1976 confirmed the importance of congenital heart disease as a determinant of early mortality. An unexplained and hitherto unreported high incidence of Sudden Death in Infancy Syndrome if survival rates with those of other investigators show, that mortality amongst cases of Down's Syndrome with no congential heart defect has decreased and longevity is no longer a rate occurrence. As a result of these changes, and despite a demonstrable fall in the incidence of Down Syndrome in Western Australia, the prevalence of the condition is expected to rise.", "contents": "Down's syndrome in Western Australia: mortality and survival. An epidemiological investigation of 231 cases of Down's Syndrome born in Western Australia between 1966 and 1976 confirmed the importance of congenital heart disease as a determinant of early mortality. An unexplained and hitherto unreported high incidence of Sudden Death in Infancy Syndrome if survival rates with those of other investigators show, that mortality amongst cases of Down's Syndrome with no congential heart defect has decreased and longevity is no longer a rate occurrence. As a result of these changes, and despite a demonstrable fall in the incidence of Down Syndrome in Western Australia, the prevalence of the condition is expected to rise."} {"id": "PMID:157825", "title": "The Burns' test in low back pain: correlation with the hysterical personality.", "content": "Twenty-five postoperative lumbar laminectomy and diskectomy patients were administered the MMPI and evaluated by physical examination which included the Burns' Bench Test. In this test the patient is asked to kneel on a bench with knees and hips flexed and place his fingers on the floor. The kneeling position relieves stress on the low back and tension on the siatic nerve, so that patients with organic causes of low back pain are able to perform the test. Conversely, inability to perform the test is indicative of functional symptoms as in hysteria. All patients were males and the average age was 54. The average interval from surgery was 2 1/2 years. Sixty-seven per cent of those patients unable to perform the Burns' test were classified as hysterical on the basis of the MMPI, while 73% of patients classified as hysterical using the MMPI criteria failed to perform the Burns' test. The correlation between the Burns' test and hysteria as determined by the MMPI was 0.48. In terms of sensitivity and specificity, the sensitivity of the Burn's test in distinguishing patients with an hysterical MMPI was 73%. The specificity for normal subjects was 71%. The Burns' test is a useful clinical test for differentiating between organic and non-organic causes of low back pain. However, the test by itself should not be construed as an unequivocal measure of hysteria as defined psychologically by the MMPI. Failure to perform the test indicates a need for further psychological study.", "contents": "The Burns' test in low back pain: correlation with the hysterical personality. Twenty-five postoperative lumbar laminectomy and diskectomy patients were administered the MMPI and evaluated by physical examination which included the Burns' Bench Test. In this test the patient is asked to kneel on a bench with knees and hips flexed and place his fingers on the floor. The kneeling position relieves stress on the low back and tension on the siatic nerve, so that patients with organic causes of low back pain are able to perform the test. Conversely, inability to perform the test is indicative of functional symptoms as in hysteria. All patients were males and the average age was 54. The average interval from surgery was 2 1/2 years. Sixty-seven per cent of those patients unable to perform the Burns' test were classified as hysterical on the basis of the MMPI, while 73% of patients classified as hysterical using the MMPI criteria failed to perform the Burns' test. The correlation between the Burns' test and hysteria as determined by the MMPI was 0.48. In terms of sensitivity and specificity, the sensitivity of the Burn's test in distinguishing patients with an hysterical MMPI was 73%. The specificity for normal subjects was 71%. The Burns' test is a useful clinical test for differentiating between organic and non-organic causes of low back pain. However, the test by itself should not be construed as an unequivocal measure of hysteria as defined psychologically by the MMPI. Failure to perform the test indicates a need for further psychological study."} {"id": "PMID:157826", "title": "The management of atlanto-axial subluxation with neurologic involvement in Down's syndrome: a report of two cases and review of the literature.", "content": "A review of 5 cases in the literature and our 2 additional cases of atlanto-axial sublux-ation in Down's Syndrome with associated neurologic deterioration suggests that posterior stabilization and fusion should be carried out initially. Posterior decompression alone, with excision of the posterior arch of C-1, may further increase atlantoaxial instability and contribute to neurologic deterioration. Lateral radiographs in flexion and extension and contrast studies are recommended to assess the reducibility of the lesion and the site of neural impingement. It is further recommended that if significant neurologic deterioration persists or worsens, an oral transpharyngeal odontoidectomy should be considered for cord decompression.", "contents": "The management of atlanto-axial subluxation with neurologic involvement in Down's syndrome: a report of two cases and review of the literature. A review of 5 cases in the literature and our 2 additional cases of atlanto-axial sublux-ation in Down's Syndrome with associated neurologic deterioration suggests that posterior stabilization and fusion should be carried out initially. Posterior decompression alone, with excision of the posterior arch of C-1, may further increase atlantoaxial instability and contribute to neurologic deterioration. Lateral radiographs in flexion and extension and contrast studies are recommended to assess the reducibility of the lesion and the site of neural impingement. It is further recommended that if significant neurologic deterioration persists or worsens, an oral transpharyngeal odontoidectomy should be considered for cord decompression."} {"id": "PMID:157828", "title": "Relaxation rate of constituent muscle-fibre types in human quadriceps.", "content": "1. Muscle fibres may be subdivided into type I (with slow-twitch contractile properties) and type II (fast-twitch) depending on their myosin adenosine triphosphatase activity. In voluntary isometric contractions type I fibres are utilized at low forces (less than 20% of maximum) whereas type II fibres are recruited in addition at high forces. This physiological recruitment order has enabled us to measure the relaxtion rate of type I and II fibres in vivo in normal human subjects. 2. Relaxation rate was measured in 16 subjects from low (10% of maximum) and maximum isometric quadriceps contractions and the muscle-fibre type composition determined from needle-biopsy specimens in 10 subjects. The relaxation rate of type II fibres was calculated to be twice as fast as that of type I. 3. It was not possible to estimate, from studies in 33 quadriceps muscles (25 normal subjects), the contribution of type II fibres to overall fibre area from the relaxation rate as determined from electrically stimulated isometric contractions.", "contents": "Relaxation rate of constituent muscle-fibre types in human quadriceps. 1. Muscle fibres may be subdivided into type I (with slow-twitch contractile properties) and type II (fast-twitch) depending on their myosin adenosine triphosphatase activity. In voluntary isometric contractions type I fibres are utilized at low forces (less than 20% of maximum) whereas type II fibres are recruited in addition at high forces. This physiological recruitment order has enabled us to measure the relaxtion rate of type I and II fibres in vivo in normal human subjects. 2. Relaxation rate was measured in 16 subjects from low (10% of maximum) and maximum isometric quadriceps contractions and the muscle-fibre type composition determined from needle-biopsy specimens in 10 subjects. The relaxation rate of type II fibres was calculated to be twice as fast as that of type I. 3. It was not possible to estimate, from studies in 33 quadriceps muscles (25 normal subjects), the contribution of type II fibres to overall fibre area from the relaxation rate as determined from electrically stimulated isometric contractions."} {"id": "PMID:157829", "title": "Cardiac effects of angiotensin antagonists in normotensive rats.", "content": "1. Angiotensin II (AII) antagonists, namely Sar1,Ile8-AII, Sar1,Ala8-AII and Sar1,Thr8-AII, were administered daily for 4 weeks to normotensive rats to study their effect on cardiac hypertrophy. 2. None of the antagonists altered blood pressure significantly but Sar1,Ile8-AII and Sar1,Ala8-AII produced a significant increase in heart weight, as compared with untreated age-matched control rats. Administration of Sar1,Thr8-AII did not produce cardiac hypertrophy. 3. A significant increase in catecholamine concentration was observed in the ventricles of rats treated with Sar1,Ile8-AII and Sar1,Ala8-AII but no change was found in the group treated with the Sar1,Thr8-AII analogue. The production of cardiac hypertrophy by Sar1,Ile8-AII was prevented by bilateral adrenalectomy, suggesting an important role for catecholamines in modulating cardiac hypertrophy.", "contents": "Cardiac effects of angiotensin antagonists in normotensive rats. 1. Angiotensin II (AII) antagonists, namely Sar1,Ile8-AII, Sar1,Ala8-AII and Sar1,Thr8-AII, were administered daily for 4 weeks to normotensive rats to study their effect on cardiac hypertrophy. 2. None of the antagonists altered blood pressure significantly but Sar1,Ile8-AII and Sar1,Ala8-AII produced a significant increase in heart weight, as compared with untreated age-matched control rats. Administration of Sar1,Thr8-AII did not produce cardiac hypertrophy. 3. A significant increase in catecholamine concentration was observed in the ventricles of rats treated with Sar1,Ile8-AII and Sar1,Ala8-AII but no change was found in the group treated with the Sar1,Thr8-AII analogue. The production of cardiac hypertrophy by Sar1,Ile8-AII was prevented by bilateral adrenalectomy, suggesting an important role for catecholamines in modulating cardiac hypertrophy."} {"id": "PMID:157830", "title": "Effect of chronic clonidine treatment and its abrupt cessation on mean blood pressure of rats with a normal or an elevated blood pressure.", "content": "1. Clonidine (6 mg of base/l of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension. 2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0.6 mg 24 h-1 kg-1) showed a sustained fall in blood pressure over 3 weeks. 3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h-1 kg-1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats. 4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats.", "contents": "Effect of chronic clonidine treatment and its abrupt cessation on mean blood pressure of rats with a normal or an elevated blood pressure. 1. Clonidine (6 mg of base/l of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension. 2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0.6 mg 24 h-1 kg-1) showed a sustained fall in blood pressure over 3 weeks. 3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h-1 kg-1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats. 4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats."} {"id": "PMID:157835", "title": "Functional analysis of the replicator structure of lambdoid bacteriophage DNAs.", "content": "In our hybrid-plasmid reconstruction analysis of lambda (lambdoid) DNA signal structures involved in phage DNA replication, we have detected a dual system alternatingly able to initiate a first primer-RNA synthesis. Both of them--the major, primase-dependent ori system and the minor and usually suppressed, RNA-polymerase-dependent oop system--act in conjunction with a common signal structure for inception of DNA synthesis. It appears that in situations such as this, where one has to deal with the existence of regular as well as backup systems serving the same function, straightforward conclusions are no longer possible in their genetic analysis. For example, even though the oop-DNA segment can be deleted entirely from bacteriophage lambda DNA without disturbing its ability to replicate, it may not be valid to conclude that the oop system has no function in DNA replication. Dual systems of this type or organization in general have also been observed previously for some other replicons such as the R-factors R6-5 and R6K (Timmis et al. 1978; Crosa et al., this volume) or the F factor (Helinski et al., this volume), and they may be more common than presently expected.", "contents": "Functional analysis of the replicator structure of lambdoid bacteriophage DNAs. In our hybrid-plasmid reconstruction analysis of lambda (lambdoid) DNA signal structures involved in phage DNA replication, we have detected a dual system alternatingly able to initiate a first primer-RNA synthesis. Both of them--the major, primase-dependent ori system and the minor and usually suppressed, RNA-polymerase-dependent oop system--act in conjunction with a common signal structure for inception of DNA synthesis. It appears that in situations such as this, where one has to deal with the existence of regular as well as backup systems serving the same function, straightforward conclusions are no longer possible in their genetic analysis. For example, even though the oop-DNA segment can be deleted entirely from bacteriophage lambda DNA without disturbing its ability to replicate, it may not be valid to conclude that the oop system has no function in DNA replication. Dual systems of this type or organization in general have also been observed previously for some other replicons such as the R-factors R6-5 and R6K (Timmis et al. 1978; Crosa et al., this volume) or the F factor (Helinski et al., this volume), and they may be more common than presently expected."} {"id": "PMID:157841", "title": "Effects of the second (ethanol) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia.", "content": "An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%), and a second (ethanol) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared for two hours. The heart rate and mean arterial pressure were significantly decreased following ginseng. There were no other meaningful changes in either group.", "contents": "Effects of the second (ethanol) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia. An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%), and a second (ethanol) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared for two hours. The heart rate and mean arterial pressure were significantly decreased following ginseng. There were no other meaningful changes in either group."} {"id": "PMID:157842", "title": "Effects of the third (aqueous) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia.", "content": "An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%) and the third (aqueous) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared. The cardiac output, stroke volume, and central venous pressure were decreased significantly, while total peripheral resistance was increased significantly following ginseng.", "contents": "Effects of the third (aqueous) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia. An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%) and the third (aqueous) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared. The cardiac output, stroke volume, and central venous pressure were decreased significantly, while total peripheral resistance was increased significantly following ginseng."} {"id": "PMID:157845", "title": "Fluorimetric determination of DNA in papain digests of cartilage, using ethidium bromide.", "content": "A fluorimetric procedure for the determination of the DNA content of cartilage is described. The tissue is initially solubilised by digestion with papain, and ethidium bromide is used for the subsequent quantitation of DNA. The basis of the procedure is the enhancement of fluorescence which occurs when ethidium bromide complexes with native nucleic acids, fluorescence due to DNA being distinguished from that due to RNA through the use of ribonuclease. The method provides reproducible results, allowing determination of DNA in papain digests containing greater than 1.25 microgram DNA/ml, and is a rapid alternative to more laborious colorimetric or fluorimetric methods, which require the separation of DNA from other tissue components. The procedure is highly specific for DNA and is useful in metabolic studies in which various parameters of chondrocyte activity are being studied.", "contents": "Fluorimetric determination of DNA in papain digests of cartilage, using ethidium bromide. A fluorimetric procedure for the determination of the DNA content of cartilage is described. The tissue is initially solubilised by digestion with papain, and ethidium bromide is used for the subsequent quantitation of DNA. The basis of the procedure is the enhancement of fluorescence which occurs when ethidium bromide complexes with native nucleic acids, fluorescence due to DNA being distinguished from that due to RNA through the use of ribonuclease. The method provides reproducible results, allowing determination of DNA in papain digests containing greater than 1.25 microgram DNA/ml, and is a rapid alternative to more laborious colorimetric or fluorimetric methods, which require the separation of DNA from other tissue components. The procedure is highly specific for DNA and is useful in metabolic studies in which various parameters of chondrocyte activity are being studied."} {"id": "PMID:157846", "title": "Effect of methods of preservation on the arrangement of collagen fibrils in connective tissue matrices: an x-ray diffraction study of annulus fibrosus.", "content": "Samples of annulus fibrosus were dissected from the anterior of lumbar intervertebral discs from adult rabbits. X-ray diffraction was used to provide a measure of the distribution of collagen fibrils in each sample. The sample was then preserved and the experiment repeated twice. Three methods of preservation were used: (1) fixation in formol saline, (2) freezing, (3) freezing in liquid nitrogen. Frozen specimens were subsequently thawed. None of the three methods of preservation affected the distribution of collagen fibrils in the tissue significantly. However, fixation does cause the collagen molecules to become more closely packed within a fibril. The method of choice for preserving annulus fibrosus and, by implication, other connective tissue matrices for ultrastructural studies is discussed.", "contents": "Effect of methods of preservation on the arrangement of collagen fibrils in connective tissue matrices: an x-ray diffraction study of annulus fibrosus. Samples of annulus fibrosus were dissected from the anterior of lumbar intervertebral discs from adult rabbits. X-ray diffraction was used to provide a measure of the distribution of collagen fibrils in each sample. The sample was then preserved and the experiment repeated twice. Three methods of preservation were used: (1) fixation in formol saline, (2) freezing, (3) freezing in liquid nitrogen. Frozen specimens were subsequently thawed. None of the three methods of preservation affected the distribution of collagen fibrils in the tissue significantly. However, fixation does cause the collagen molecules to become more closely packed within a fibril. The method of choice for preserving annulus fibrosus and, by implication, other connective tissue matrices for ultrastructural studies is discussed."} {"id": "PMID:157847", "title": "The effect of contaminant proteases in testicular hyaluronidase preparations on the immunological properties of bovine nasal cartilage proteoglycan.", "content": "Commercial testicular hyaluronidase preparations are contaminated by a small amount of protease activity which is partially inhibited by serine-protease inhibitors or pepstatin. These protease inhibitors can be shown by Sepharose gel column chromatography to abolish or reduce hyaluronidase-induced degradation of bovine nasal cartilage proteoglycan subunit without affecting the ability of the enzyme to degrade chondroitin sulfate. In addition, immunodiffusion studies indicate that pretreatment of hyaluronidase with these protease inhibitors reduces or abolishes the ability of the enzyme to produce a second \"link-related\" immunoprecipitin line upon digestion of link protein-containing proteoglycan fractions. Thus, the enhancement of immune reactivity and the unmasking of an additional antigen noted after digestion of cartilage proteoglycan with testicular hyaluronidase are most likely due to the exposure of additional antigenic sites or the the release of more highly immunoreactive fragments by the contaminant proteases rather than to the action of hyaluronidase itself.", "contents": "The effect of contaminant proteases in testicular hyaluronidase preparations on the immunological properties of bovine nasal cartilage proteoglycan. Commercial testicular hyaluronidase preparations are contaminated by a small amount of protease activity which is partially inhibited by serine-protease inhibitors or pepstatin. These protease inhibitors can be shown by Sepharose gel column chromatography to abolish or reduce hyaluronidase-induced degradation of bovine nasal cartilage proteoglycan subunit without affecting the ability of the enzyme to degrade chondroitin sulfate. In addition, immunodiffusion studies indicate that pretreatment of hyaluronidase with these protease inhibitors reduces or abolishes the ability of the enzyme to produce a second \"link-related\" immunoprecipitin line upon digestion of link protein-containing proteoglycan fractions. Thus, the enhancement of immune reactivity and the unmasking of an additional antigen noted after digestion of cartilage proteoglycan with testicular hyaluronidase are most likely due to the exposure of additional antigenic sites or the the release of more highly immunoreactive fragments by the contaminant proteases rather than to the action of hyaluronidase itself."} {"id": "PMID:157848", "title": "The content of dityrosine in chick and rabbit aorta proteins.", "content": "The possible presence of dityrosine in elastin derived by two different methods and in structural glycoproteins from aortas of 1 day old chicks, adult rabbits and fetal rabbits was determined by a sensitive spectrofluorimetric procedure. Only chick tissues were found to contain dityrosine, 0.3 residues/100,000 total amino acid residues in aortic elastin and 12-15 residues/100,000 residues in the structural glycoproteins. No dityrosine could be detected in any of the fetal or mature rabbit tissues. However, related fluorescent compounds with different excitation-emission maxima and different elution times were obtained by ion exchange chromatography of structural glycoproteins partially hydrolyzed under alkaline conditions.", "contents": "The content of dityrosine in chick and rabbit aorta proteins. The possible presence of dityrosine in elastin derived by two different methods and in structural glycoproteins from aortas of 1 day old chicks, adult rabbits and fetal rabbits was determined by a sensitive spectrofluorimetric procedure. Only chick tissues were found to contain dityrosine, 0.3 residues/100,000 total amino acid residues in aortic elastin and 12-15 residues/100,000 residues in the structural glycoproteins. No dityrosine could be detected in any of the fetal or mature rabbit tissues. However, related fluorescent compounds with different excitation-emission maxima and different elution times were obtained by ion exchange chromatography of structural glycoproteins partially hydrolyzed under alkaline conditions."} {"id": "PMID:157850", "title": "Topical clindamycin in acne: a preliminary study.", "content": "A solution of clindamycin in 50 percent alcohol used topically in the treatment of acne was found to be an adequate therapy to replace systemic tetracycline. Patients followed over a two to three month period showed improvement in lesion counts and subjective improvement as evaluated by the investigator and patient.", "contents": "Topical clindamycin in acne: a preliminary study. A solution of clindamycin in 50 percent alcohol used topically in the treatment of acne was found to be an adequate therapy to replace systemic tetracycline. Patients followed over a two to three month period showed improvement in lesion counts and subjective improvement as evaluated by the investigator and patient."} {"id": "PMID:157852", "title": "Psoriasiform eruption induced by propranolol.", "content": "The appearance of a psoriasiform eruption in a seventy-eight year old patient after one year of treatment with propranolol is presented herein. The histologic picture was not compatible with psoriasis vulgaris, although it contained some of the same features. Immunologic investigation revealed immune deposits at the junction of the dermis and epidermis and in blood vessel walls as well as monoclonal gammopathy. The rash, which was followed by a reduction in tear secretion, is suggested to have been a drug reaction associated with propranolol. This is supported by the positive results of a migration inhibiting factor test towards propranolol, the clearing of the eruption which took place three weeks after withdrawal of the drug, and the negative result of the same test obtained soon afterwards.", "contents": "Psoriasiform eruption induced by propranolol. The appearance of a psoriasiform eruption in a seventy-eight year old patient after one year of treatment with propranolol is presented herein. The histologic picture was not compatible with psoriasis vulgaris, although it contained some of the same features. Immunologic investigation revealed immune deposits at the junction of the dermis and epidermis and in blood vessel walls as well as monoclonal gammopathy. The rash, which was followed by a reduction in tear secretion, is suggested to have been a drug reaction associated with propranolol. This is supported by the positive results of a migration inhibiting factor test towards propranolol, the clearing of the eruption which took place three weeks after withdrawal of the drug, and the negative result of the same test obtained soon afterwards."} {"id": "PMID:157853", "title": "Cutaneous reaction to spironolactone resembling lupus erythematosus.", "content": "A cirrhotic male patient was admitted with a skin eruption. He had been taking spironolactone and hydrochlorothiazide for two months prior to admission. The morphology and distribution of skin lesions resembled that of systemic lupus erythematosus (SLE). Histologic changes in the skin biopsy specimen were consistent with SLE. Biopsy specimens of normal and affected skin were reported to show weak focal deposition of IgM and complement at the dermal-epidermal junction. However, there was a striking absence of serologic evidence of SLE. The rash disappeared when all medications were discontinued and reappeared when the patient was given spironolactone. The character and distribution of the rash after spironolactone administration was identical to the previous lesions. It disappeared again when spironolactone was withdrawn. This response to spironolactone is good evidence that it and not chlorothiazide was responsible for the rash. The latter drug has been reported to cause SLE-like skin changes.", "contents": "Cutaneous reaction to spironolactone resembling lupus erythematosus. A cirrhotic male patient was admitted with a skin eruption. He had been taking spironolactone and hydrochlorothiazide for two months prior to admission. The morphology and distribution of skin lesions resembled that of systemic lupus erythematosus (SLE). Histologic changes in the skin biopsy specimen were consistent with SLE. Biopsy specimens of normal and affected skin were reported to show weak focal deposition of IgM and complement at the dermal-epidermal junction. However, there was a striking absence of serologic evidence of SLE. The rash disappeared when all medications were discontinued and reappeared when the patient was given spironolactone. The character and distribution of the rash after spironolactone administration was identical to the previous lesions. It disappeared again when spironolactone was withdrawn. This response to spironolactone is good evidence that it and not chlorothiazide was responsible for the rash. The latter drug has been reported to cause SLE-like skin changes."} {"id": "PMID:157854", "title": "Vitamin B-12 induced acnes.", "content": "A type of acne induced by vitamin B-12 deserves a special place among acneiform eruptions. The eruption is monomorphic and of a particular type. It consists of voluminous folliculitis lesions which develop acutely after the first injections of vitamin B-12 and disappear rapidly when treatment is discontinued. The etiologic and pathogenic mechanisms of the disease are not know.", "contents": "Vitamin B-12 induced acnes. A type of acne induced by vitamin B-12 deserves a special place among acneiform eruptions. The eruption is monomorphic and of a particular type. It consists of voluminous folliculitis lesions which develop acutely after the first injections of vitamin B-12 and disappear rapidly when treatment is discontinued. The etiologic and pathogenic mechanisms of the disease are not know."} {"id": "PMID:157855", "title": "Biofeedback training in the therapy of dyshidrosis.", "content": "Biofeedback training for hand warming and relaxation was used with five patients with severe dyshidrotic eczema who were poorly responsive to conventional therapy. Improvement was seen in all five patients, especially those who most noted flaring of their disease under stress. Biofeedback is being used in the treatment of diverse stress-related disorders, and may have potential in dermatologic diseases.", "contents": "Biofeedback training in the therapy of dyshidrosis. Biofeedback training for hand warming and relaxation was used with five patients with severe dyshidrotic eczema who were poorly responsive to conventional therapy. Improvement was seen in all five patients, especially those who most noted flaring of their disease under stress. Biofeedback is being used in the treatment of diverse stress-related disorders, and may have potential in dermatologic diseases."} {"id": "PMID:157856", "title": "Cutaneous reaction rates to penicillins--oral versus parenteral.", "content": "Rates of skin reactions for oral and parenteral administration of various types of penicillin were compared in an extensive series of carefully monitored patients. The rate with orally administered penicillins was consistently lower than when administered parenterally.", "contents": "Cutaneous reaction rates to penicillins--oral versus parenteral. Rates of skin reactions for oral and parenteral administration of various types of penicillin were compared in an extensive series of carefully monitored patients. The rate with orally administered penicillins was consistently lower than when administered parenterally."} {"id": "PMID:157859", "title": "Partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum.", "content": "A five-year-old girl with partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum is reported. The clinical and roentgenographic features suggested the correct diagnosis. Surgical correction of this previously unreported defect was accomplished by creating an atrial septal defect and constructing a baffle to direct the blood flow from the azygous vein to the left atrium.", "contents": "Partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum. A five-year-old girl with partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum is reported. The clinical and roentgenographic features suggested the correct diagnosis. Surgical correction of this previously unreported defect was accomplished by creating an atrial septal defect and constructing a baffle to direct the blood flow from the azygous vein to the left atrium."} {"id": "PMID:157865", "title": "[Contact eczema caused by isonicotinic acid hydrazide].", "content": "In the treatment of an ulcerous reaction to BCG vaccination with isonicotinic acid hydrazide cones, a 20 year old nurse developed a contact eczema within four weeks under the influence of this tuberculostatic.", "contents": "[Contact eczema caused by isonicotinic acid hydrazide]. In the treatment of an ulcerous reaction to BCG vaccination with isonicotinic acid hydrazide cones, a 20 year old nurse developed a contact eczema within four weeks under the influence of this tuberculostatic."} {"id": "PMID:157866", "title": "[Decrease of earning capacity. Results of evaluation of proposals for the estimation of earning capacity decrease in occupational disease according to No.5101 of the Occupational Diseases Act].", "content": "The table elaborated for estimating the diminution of earning capacity has proved useful. A questionnaire programme revealed that classification of occupational dermatological disorders becomes a problem as soon as insurance-legal factors have to be considered.", "contents": "[Decrease of earning capacity. Results of evaluation of proposals for the estimation of earning capacity decrease in occupational disease according to No.5101 of the Occupational Diseases Act]. The table elaborated for estimating the diminution of earning capacity has proved useful. A questionnaire programme revealed that classification of occupational dermatological disorders becomes a problem as soon as insurance-legal factors have to be considered."} {"id": "PMID:157867", "title": "[Actinic reticuloid in a florist].", "content": "Actinic Reticuloid in a Florist A 63 year old florist developed after primary sensibilisation against Chrysanthemum and other flowers and plants the typical clinical and histological features of an actinic reticuloid with considerably augmented sensitivity to UV A and UV B.", "contents": "[Actinic reticuloid in a florist]. Actinic Reticuloid in a Florist A 63 year old florist developed after primary sensibilisation against Chrysanthemum and other flowers and plants the typical clinical and histological features of an actinic reticuloid with considerably augmented sensitivity to UV A and UV B."} {"id": "PMID:157869", "title": "[Contraception in androgenised women with a low-dose cyproterone-acetate containing one-phase preparation (author's transl)].", "content": "101 hirsute women received Diane, a combination of 2 mg cyproterone acetate and 50 micrograms ethinyl oestradiol per capsule, from the fifth to twenty-fifth day during a total of 1105 cycles. The treatment was satisfactory in 96% of women with acne, 84% with androgenic alopecia, 79% with seborrhoea, and 50% of those with mild or moderate hirsutism. The effectiveness of treating hirsutism or alopecia depended on its severity and duration. There was no correlation between various measures of androgen levels before and during treatment and the clinical results. Side effects were similar to those after contraceptive one-phase preparations, both in kind and incidence. None of the women became pregnant. Diane is thus the drug of choice in hormonal contraception of patients with acne, seborrhoea, androgenic alopecia or mild hirsutism. It is also suitable in the follow-up or interval management of high-dose cyproterone acetate treatment of severe hirsutism, in order to maintain the effect obtained with lower hormone doses.", "contents": "[Contraception in androgenised women with a low-dose cyproterone-acetate containing one-phase preparation (author's transl)]. 101 hirsute women received Diane, a combination of 2 mg cyproterone acetate and 50 micrograms ethinyl oestradiol per capsule, from the fifth to twenty-fifth day during a total of 1105 cycles. The treatment was satisfactory in 96% of women with acne, 84% with androgenic alopecia, 79% with seborrhoea, and 50% of those with mild or moderate hirsutism. The effectiveness of treating hirsutism or alopecia depended on its severity and duration. There was no correlation between various measures of androgen levels before and during treatment and the clinical results. Side effects were similar to those after contraceptive one-phase preparations, both in kind and incidence. None of the women became pregnant. Diane is thus the drug of choice in hormonal contraception of patients with acne, seborrhoea, androgenic alopecia or mild hirsutism. It is also suitable in the follow-up or interval management of high-dose cyproterone acetate treatment of severe hirsutism, in order to maintain the effect obtained with lower hormone doses."} {"id": "PMID:157871", "title": "Participation of serotonin in thyrotropin release. II. Evidence for the action of serotonin on the phasic release of thyrotropin.", "content": "During a 12-h light 12-h dark schedule (lights off at 1900 h), male Sprague-Dawley rats show a circadian rhythm of plasma TSH with a zenith near midday. The participation of serotonin (5HT) in the phasic release of TSH was studied using both pharmacological and surgical-stereotaxical approaches. Animals treated with parachlorophenylalanine methyl ester (pCPA), an inhibitor of 5HT synthesis (one or two injections of 250 mg/kg each) showed a reduction or a disappearance of the diurnal peak of TSH, respectively. Additional treatment by 5-hydroxytryptophan, a precursor of 5HT, completely, restored the diurnal TSH peak. Treatment with 5,6-dihydroxytryptamine creatine sulfate, a neurotoxin which selectively destroys 5HT terminals, also induced alterations of the diurnal peak of TSH. There were no major modifications observed in the low nocturnal levels of TSH in rats treated with pCPA, 5-hydroxytryptophan, or 5,6-dihydroxytryptamine. The major serotoninergic innervation of the hypothalamus originates from the raphe dorsalis or centralis; destruction of these two nuclei caused a quasiabolition of the diurnal TSH peak (only a low amplitude TSH circadian rhythm persisted). Hypothalamic 5HT content was measured in the majority of these experiments; the greatest depletions (near 90%) were observed after two injections of pCPA or in rats bearing raphe lesions. We conclude that the diurnal peak of TSH, observed during the physiological circadian rhythm, is serotoninergic dependent.", "contents": "Participation of serotonin in thyrotropin release. II. Evidence for the action of serotonin on the phasic release of thyrotropin. During a 12-h light 12-h dark schedule (lights off at 1900 h), male Sprague-Dawley rats show a circadian rhythm of plasma TSH with a zenith near midday. The participation of serotonin (5HT) in the phasic release of TSH was studied using both pharmacological and surgical-stereotaxical approaches. Animals treated with parachlorophenylalanine methyl ester (pCPA), an inhibitor of 5HT synthesis (one or two injections of 250 mg/kg each) showed a reduction or a disappearance of the diurnal peak of TSH, respectively. Additional treatment by 5-hydroxytryptophan, a precursor of 5HT, completely, restored the diurnal TSH peak. Treatment with 5,6-dihydroxytryptamine creatine sulfate, a neurotoxin which selectively destroys 5HT terminals, also induced alterations of the diurnal peak of TSH. There were no major modifications observed in the low nocturnal levels of TSH in rats treated with pCPA, 5-hydroxytryptophan, or 5,6-dihydroxytryptamine. The major serotoninergic innervation of the hypothalamus originates from the raphe dorsalis or centralis; destruction of these two nuclei caused a quasiabolition of the diurnal TSH peak (only a low amplitude TSH circadian rhythm persisted). Hypothalamic 5HT content was measured in the majority of these experiments; the greatest depletions (near 90%) were observed after two injections of pCPA or in rats bearing raphe lesions. We conclude that the diurnal peak of TSH, observed during the physiological circadian rhythm, is serotoninergic dependent."} {"id": "PMID:157873", "title": "A controlled study of prednisone therapy in infantile spasms.", "content": "A controlled study of 12 patients with infantile spasms was performed to determine the effectiveness of prednisone treatment. Patients were monitored serially, using a time-synchronized polygraphic and video system. Three patients (25%) showed prompt reduction in seizure frequency and normalization of the EEG after institution of treatment. The remaining patients showed no improvement in seizure frequency or significant change in the EEG.", "contents": "A controlled study of prednisone therapy in infantile spasms. A controlled study of 12 patients with infantile spasms was performed to determine the effectiveness of prednisone treatment. Patients were monitored serially, using a time-synchronized polygraphic and video system. Three patients (25%) showed prompt reduction in seizure frequency and normalization of the EEG after institution of treatment. The remaining patients showed no improvement in seizure frequency or significant change in the EEG."} {"id": "PMID:157874", "title": "An outbreak of eosinophilic bronchitis in horses possibly associated with Dictyocaulus arnfieldi infection.", "content": "Eight mature horses which had been affected with a moist cough for six weeks were found to have large numbers of eosinophils in tracheal mucus samples taken by transtracheal washing. These horses were kept on irrigated pasture and fed a hay-free diet. A companion yearling donkey was found to be passing Dictyocaulus arnfieldi larvae in its faeces. Two oral treatments with a dose of thiabendazole (440 mg/kg) resulted in the resolution of the clinical signs and the disappearance of eosinophils from transtracheal washings. The eosinophilic bronchitis seen in these horses was presumed to be a manifestation of prepatent D arnfieldi infestation.", "contents": "An outbreak of eosinophilic bronchitis in horses possibly associated with Dictyocaulus arnfieldi infection. Eight mature horses which had been affected with a moist cough for six weeks were found to have large numbers of eosinophils in tracheal mucus samples taken by transtracheal washing. These horses were kept on irrigated pasture and fed a hay-free diet. A companion yearling donkey was found to be passing Dictyocaulus arnfieldi larvae in its faeces. Two oral treatments with a dose of thiabendazole (440 mg/kg) resulted in the resolution of the clinical signs and the disappearance of eosinophils from transtracheal washings. The eosinophilic bronchitis seen in these horses was presumed to be a manifestation of prepatent D arnfieldi infestation."} {"id": "PMID:157875", "title": "Ionized and bound calcium inside isolated sarcoplasmic reticulum of skeletal muscle and its significance in phosphorylation of adenosine triphosphatase by orthophosphate.", "content": "Calcium loading of skeletal muscle sarcoplasmic reticulum performed passively by incubation with high calcium concentrations (0.5--15 mM) on ice gives calcium loads of 50--60 nmol/mg sarcoplasmic reticulum protein. This accumulated calcium is not released by EGTA [ethyleneglycol bis-(2-aminoethyl)-N,N,N',N'-tetraacetic acid], but almost completely released by ionophore X-537A plus EGTA or phospholipase A plus EGTA treatment and is therefore assumed to be inside the sarcoplasmic reticulum. This calcium is distributed in one saturable and one non-saturable calcium compartment, as derived from the dependence of the calcium load on the calcium concentration in the medium. These compartments are assigned to bound and ionized calcium inside the sarcoplasmic reticulum, respectively. Maximum calcium binding under these conditions was 33 nmol/mg protein with an apparent half-saturation constant of 5,8 nmol/mg free calcium inside, or between 1.2 and 0.6 mM free calcium inside, assuming an average vesicular water space of 5 or 10 microliter/mg protein, respectively. Calcium-dependent phosphorylation of sarcoplasmic reticulum calcium-transport ATPase from orthophosphate depends on the square of free calcium inside, whilst inhibition of phosphorylation depends on the square of free calcium in the medium. Calcium-dependent phosphorylation appears to be determined by the free calcium concentrations inside or outside allowing calcium binding to the ATPase according to the two classes of calcium binding constants for low affinity calcium binding or high affinity calcium binding, respectively. It is further suggested that the saturation of the low-affinity calcium-binding sites of the ATPase facing the inside of the sarcoplasmic reticulum membrane is responsible for the greater apparent orthophosphate and magnesium affinity in calcium-dependent phosphorylation than in calcium-independent phosphorylation from orthophosphate. Maximum calcium-dependent phosphoprotein formation at 20 degrees C and pH 7.0 is about 4 nmol/mg sarcoplasmic reticulum protein.", "contents": "Ionized and bound calcium inside isolated sarcoplasmic reticulum of skeletal muscle and its significance in phosphorylation of adenosine triphosphatase by orthophosphate. Calcium loading of skeletal muscle sarcoplasmic reticulum performed passively by incubation with high calcium concentrations (0.5--15 mM) on ice gives calcium loads of 50--60 nmol/mg sarcoplasmic reticulum protein. This accumulated calcium is not released by EGTA [ethyleneglycol bis-(2-aminoethyl)-N,N,N',N'-tetraacetic acid], but almost completely released by ionophore X-537A plus EGTA or phospholipase A plus EGTA treatment and is therefore assumed to be inside the sarcoplasmic reticulum. This calcium is distributed in one saturable and one non-saturable calcium compartment, as derived from the dependence of the calcium load on the calcium concentration in the medium. These compartments are assigned to bound and ionized calcium inside the sarcoplasmic reticulum, respectively. Maximum calcium binding under these conditions was 33 nmol/mg protein with an apparent half-saturation constant of 5,8 nmol/mg free calcium inside, or between 1.2 and 0.6 mM free calcium inside, assuming an average vesicular water space of 5 or 10 microliter/mg protein, respectively. Calcium-dependent phosphorylation of sarcoplasmic reticulum calcium-transport ATPase from orthophosphate depends on the square of free calcium inside, whilst inhibition of phosphorylation depends on the square of free calcium in the medium. Calcium-dependent phosphorylation appears to be determined by the free calcium concentrations inside or outside allowing calcium binding to the ATPase according to the two classes of calcium binding constants for low affinity calcium binding or high affinity calcium binding, respectively. It is further suggested that the saturation of the low-affinity calcium-binding sites of the ATPase facing the inside of the sarcoplasmic reticulum membrane is responsible for the greater apparent orthophosphate and magnesium affinity in calcium-dependent phosphorylation than in calcium-independent phosphorylation from orthophosphate. Maximum calcium-dependent phosphoprotein formation at 20 degrees C and pH 7.0 is about 4 nmol/mg sarcoplasmic reticulum protein."} {"id": "PMID:157876", "title": "Turnover rates of hexokinase I, phosphofructokinase, pyruvate kinase and creatine kinase in slow-twitch soleus muscle and heart of the rabbit.", "content": "Hexokinase I was purified from rabbit heart to a specific activity of 70 U/mg protein. The purified enzyme was electrophoretically homogeneous with an apparent molecular weight of 102,000. Purified immunoglobulins from sheep were used to titrate the percentage of hexokinase I in various tissues of the rabbit. Precipitating antibodies from sheep were also prepared against rabbit muscle MM-creatine kinase, phosphofructokinase and pyruvate kinase. Apparent turnover rates of these phosphotransferases and of hexokinase I were determined in rabbit heart and soleus muscle by means of the immunoprecipitation technique after single pulse labelling with [U-14Cl]leucine in vivo. Apparent half-lives of phosphofructokinase, pyruvate kinase and hexokinase I were 0.56 d, 0.73 d and 0.93 d in rabbit heart. In slow-twitch soleus muscle half-lives of phosphofructokinase, pyruvate kinase, hexokinase II and creatine kinase were 0.63 d, 0.72 d, 0.85 d and 0.82 d. The similarity of the rate constants of degradation of these enzymes is interpreted as an indication that different tissue concentrations result primarily from different rates of synthesis.", "contents": "Turnover rates of hexokinase I, phosphofructokinase, pyruvate kinase and creatine kinase in slow-twitch soleus muscle and heart of the rabbit. Hexokinase I was purified from rabbit heart to a specific activity of 70 U/mg protein. The purified enzyme was electrophoretically homogeneous with an apparent molecular weight of 102,000. Purified immunoglobulins from sheep were used to titrate the percentage of hexokinase I in various tissues of the rabbit. Precipitating antibodies from sheep were also prepared against rabbit muscle MM-creatine kinase, phosphofructokinase and pyruvate kinase. Apparent turnover rates of these phosphotransferases and of hexokinase I were determined in rabbit heart and soleus muscle by means of the immunoprecipitation technique after single pulse labelling with [U-14Cl]leucine in vivo. Apparent half-lives of phosphofructokinase, pyruvate kinase and hexokinase I were 0.56 d, 0.73 d and 0.93 d in rabbit heart. In slow-twitch soleus muscle half-lives of phosphofructokinase, pyruvate kinase, hexokinase II and creatine kinase were 0.63 d, 0.72 d, 0.85 d and 0.82 d. The similarity of the rate constants of degradation of these enzymes is interpreted as an indication that different tissue concentrations result primarily from different rates of synthesis."} {"id": "PMID:157877", "title": "In vivo exploration of the tensile strength of the abdominal wall after repair with different prosthetic materials. Experimental study in the rat.", "content": "The problem of parietal herniation seems to be a simple mechanical one for which there should be a safe method of repair. In the present study, the bursting strength of abdominal wounds was explored by mechanical investigation and the repair process evaluated at a cellular level by quantitative microscopy. Both methods of investigation show that mesh materials have advantages over nonporous cloth materials in the repair of large defects of the abdominal wall.", "contents": "In vivo exploration of the tensile strength of the abdominal wall after repair with different prosthetic materials. Experimental study in the rat. The problem of parietal herniation seems to be a simple mechanical one for which there should be a safe method of repair. In the present study, the bursting strength of abdominal wounds was explored by mechanical investigation and the repair process evaluated at a cellular level by quantitative microscopy. Both methods of investigation show that mesh materials have advantages over nonporous cloth materials in the repair of large defects of the abdominal wall."} {"id": "PMID:157880", "title": "Alterations of the nucleus ruber in 3-acetylpyridine intoxication. A light and electron microscopic study.", "content": "3-acetylpyridine (3-AP) given in one single dose near to LD50 causes hydropic-vacuolic degeneration and cellular necrosis of varying degree and extension in the red nucleus of white rats in more than 50 percent of the cases. Less frequently similar alterations have been observed in some neighbouring nuclei of the mesencephalon. The regressive damage is remarkably rare if a smaller dose of 3-AP is given and none if the animal is pretreated with nicotine amide. Ultrastructurally the damage of mitochondria is dominant, they might be transformed to cystic lamellar figures. One reason of the enhanced vulnerability to antimetabolite is the outstanding enzyme activity of the red nucleus. In some of the intoxicated animals the six oxidative enzymes tested histochemically show different type of alterations which probably are related to the regressive damage.", "contents": "Alterations of the nucleus ruber in 3-acetylpyridine intoxication. A light and electron microscopic study. 3-acetylpyridine (3-AP) given in one single dose near to LD50 causes hydropic-vacuolic degeneration and cellular necrosis of varying degree and extension in the red nucleus of white rats in more than 50 percent of the cases. Less frequently similar alterations have been observed in some neighbouring nuclei of the mesencephalon. The regressive damage is remarkably rare if a smaller dose of 3-AP is given and none if the animal is pretreated with nicotine amide. Ultrastructurally the damage of mitochondria is dominant, they might be transformed to cystic lamellar figures. One reason of the enhanced vulnerability to antimetabolite is the outstanding enzyme activity of the red nucleus. In some of the intoxicated animals the six oxidative enzymes tested histochemically show different type of alterations which probably are related to the regressive damage."} {"id": "PMID:157881", "title": "Appearance of growth-inhibiting activity (G1 chalone) during ontogenetic development of rat and chick epidermis in vivo and in vitro.", "content": "A comparative study was carried out between the stage of embryonic development of epidermis and its content of growth-inhibitory activity (G1 chalone). Injections of aqueous extracts from keratinized fetal rat or chick embryo epidermis led to a depression of DNA-synthesis in adult mouse epidermis, whereas extracts from undifferentiated epidermis did not contain such an activity.", "contents": "Appearance of growth-inhibiting activity (G1 chalone) during ontogenetic development of rat and chick epidermis in vivo and in vitro. A comparative study was carried out between the stage of embryonic development of epidermis and its content of growth-inhibitory activity (G1 chalone). Injections of aqueous extracts from keratinized fetal rat or chick embryo epidermis led to a depression of DNA-synthesis in adult mouse epidermis, whereas extracts from undifferentiated epidermis did not contain such an activity."} {"id": "PMID:157882", "title": "Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats.", "content": "Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.", "contents": "Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats. Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow."} {"id": "PMID:157883", "title": "[Decurarization using the cation-anion molecular interaction of a myorelaxant and its antagonist].", "content": "In experiments on the cat neuromuscular preparation the authors investigated the anticurare action of the new compound IEM-931 having sulphonate-anionic groups 20 A apart. The new compound administered in a dose of 184 mkM/kg prevents and removes the curare effect of rythetronium which is its structural analogue. Regarding tubocurarine the antagonism is displayed, however, only from the dose of 384 mkM/kg. This indicates that efficacy of the anticurare action of IEM-931 is directly related to complimentarity of the interacting molecule structure. The experiment with regional relaxation of the cat muscles shows that the anticurare action of IEM-931 is realized both in the blood and on the cholinoreceptor. Moreover, as a result of molecular interaction the inactive complex is formed.", "contents": "[Decurarization using the cation-anion molecular interaction of a myorelaxant and its antagonist]. In experiments on the cat neuromuscular preparation the authors investigated the anticurare action of the new compound IEM-931 having sulphonate-anionic groups 20 A apart. The new compound administered in a dose of 184 mkM/kg prevents and removes the curare effect of rythetronium which is its structural analogue. Regarding tubocurarine the antagonism is displayed, however, only from the dose of 384 mkM/kg. This indicates that efficacy of the anticurare action of IEM-931 is directly related to complimentarity of the interacting molecule structure. The experiment with regional relaxation of the cat muscles shows that the anticurare action of IEM-931 is realized both in the blood and on the cholinoreceptor. Moreover, as a result of molecular interaction the inactive complex is formed."} {"id": "PMID:157889", "title": "The sensitizing capacity of Compositae plants. III. Test results and cross-reactions in Compositae-sensitive patients.", "content": "25 patients known or suspected to be allergic to different Compositae plants were tested epicutaneously with ether extracts of different Compositae species. 14 persons revealed a chrysanthemum hypersensitivity, 2 were allergic to arnica and 2 to camomile. In 1 patient a positive reaction to tansy was obtained. In the case of the chrysanthemum allergy, this was induced occupationally. All other patients had sensitized themselves by non-occupational contact. Cross-reactions were seen to tansy [14], yarrow [11], camomile [10], arnica and sunflower [5]. The components which are responsible for the sensitization as well as for the crossreactions are sesquiterpene lactones.", "contents": "The sensitizing capacity of Compositae plants. III. Test results and cross-reactions in Compositae-sensitive patients. 25 patients known or suspected to be allergic to different Compositae plants were tested epicutaneously with ether extracts of different Compositae species. 14 persons revealed a chrysanthemum hypersensitivity, 2 were allergic to arnica and 2 to camomile. In 1 patient a positive reaction to tansy was obtained. In the case of the chrysanthemum allergy, this was induced occupationally. All other patients had sensitized themselves by non-occupational contact. Cross-reactions were seen to tansy [14], yarrow [11], camomile [10], arnica and sunflower [5]. The components which are responsible for the sensitization as well as for the crossreactions are sesquiterpene lactones."} {"id": "PMID:157884", "title": "[Experimental study of the action of Bunium persicum oil on the functional state of the liver and pancreas].", "content": "The effect of Bunium Persicum oil on the indices of lipid-lipoid and protein-nitrogen metabolism and of the enzymes (histidase, arginase, transamidinase, trypsin and trypsin inhibitor) reflecting the function of the liver and pancreas was studied in experiments on white rats. There was an improvement of the indices of protein nitrogen metabolism in administration of the oil alone and combined with ethanol and CCl4. At the same time the content of total lipids and cholesterol in the blood serum and in the liver increased. The activity of the enzymes of the blood serum, liver homogenates and the pancreas reflected organ specificity and changed simultaneously with alterations in the general trend of the metabolism.", "contents": "[Experimental study of the action of Bunium persicum oil on the functional state of the liver and pancreas]. The effect of Bunium Persicum oil on the indices of lipid-lipoid and protein-nitrogen metabolism and of the enzymes (histidase, arginase, transamidinase, trypsin and trypsin inhibitor) reflecting the function of the liver and pancreas was studied in experiments on white rats. There was an improvement of the indices of protein nitrogen metabolism in administration of the oil alone and combined with ethanol and CCl4. At the same time the content of total lipids and cholesterol in the blood serum and in the liver increased. The activity of the enzymes of the blood serum, liver homogenates and the pancreas reflected organ specificity and changed simultaneously with alterations in the general trend of the metabolism."} {"id": "PMID:157890", "title": "Two cases of penicillamine-induced pemphigus erythematosus.", "content": "2 women, 62 and 69 years old, both suffering from rheumatoid arthritis, were treated for 1 and 1 1/2 years, respectively, with penicillamine. Both developed a bullous eruption which according to clinical and histological picture, immunofluorescence studies and to light provocation, as well as in 1 case to antinuclear antibody findings corresponded to pemphigus erythematosus. In spite of treatment with prednisone and azathioprine, they still keep developing bullae.", "contents": "Two cases of penicillamine-induced pemphigus erythematosus. 2 women, 62 and 69 years old, both suffering from rheumatoid arthritis, were treated for 1 and 1 1/2 years, respectively, with penicillamine. Both developed a bullous eruption which according to clinical and histological picture, immunofluorescence studies and to light provocation, as well as in 1 case to antinuclear antibody findings corresponded to pemphigus erythematosus. In spite of treatment with prednisone and azathioprine, they still keep developing bullae."} {"id": "PMID:157891", "title": "Neutrophil functions in acne conglobata.", "content": "Chemotaxis, random migration, phagocytosis, spontaneous and stimulated NBT reduction were evaluated in neutrophils from the peripheral blood of 8 patients with acne conglobata and were found to be normal. Only 2 patients had an increased spontaneous NBT reduction, and another exhibited a defect in neutrophil adhesiveness. On this basis, intrinsic defects of the major neutrophil functions, as evaluated in vitro, can be excluded in acne conglobata.", "contents": "Neutrophil functions in acne conglobata. Chemotaxis, random migration, phagocytosis, spontaneous and stimulated NBT reduction were evaluated in neutrophils from the peripheral blood of 8 patients with acne conglobata and were found to be normal. Only 2 patients had an increased spontaneous NBT reduction, and another exhibited a defect in neutrophil adhesiveness. On this basis, intrinsic defects of the major neutrophil functions, as evaluated in vitro, can be excluded in acne conglobata."} {"id": "PMID:157892", "title": "Epidermodysplasia verruciformis in Nigerians.", "content": "An analysis of the clinical and pathologic characteristics of 12 Nigerian patients with epidermodysplasia verruciformis (EV) is presented. Two morphological variants have been observed, typical wart-like flat-topped papules and larger confluent plaques. Seborrhoeic keratoses were observed in patients with the second morphological variety of EV. Solar elastosis was found in biopsies taken from EV lesions in this subgroup of patients. A particular rarity of seborrhoeic keratosis in Africans is emphasized as no single African case of seborrhoeic keratosis was found apart from patients with EV. No malignant epithelial skin tumours were found in the whole group. Factors underlying an apparently more benign course of EV in Africans are discussed, and the literature on EV in African is reviewed.", "contents": "Epidermodysplasia verruciformis in Nigerians. An analysis of the clinical and pathologic characteristics of 12 Nigerian patients with epidermodysplasia verruciformis (EV) is presented. Two morphological variants have been observed, typical wart-like flat-topped papules and larger confluent plaques. Seborrhoeic keratoses were observed in patients with the second morphological variety of EV. Solar elastosis was found in biopsies taken from EV lesions in this subgroup of patients. A particular rarity of seborrhoeic keratosis in Africans is emphasized as no single African case of seborrhoeic keratosis was found apart from patients with EV. No malignant epithelial skin tumours were found in the whole group. Factors underlying an apparently more benign course of EV in Africans are discussed, and the literature on EV in African is reviewed."} {"id": "PMID:157893", "title": "Percutaneous absorption of clioquinol (Vioform).", "content": "The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.", "contents": "Percutaneous absorption of clioquinol (Vioform). The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose."} {"id": "PMID:157903", "title": "[The endocardial ventricular activation map in a case of intermittent BBS in phase III (author's transl)].", "content": "To obtain information on endocardial activation-sequence, unipolar recordings at seven left ventricular and six right ventricular points were performed in a 37-year-old man suffering from cardiomyopathy and tachycardia-dependent left bundle branch block (LBBB). Results were as follows: 1) the recovery time was longer in anterior than in posterior portion of left bundle branch fibers; 2) an high posterior left ventricular point was directly activated via posterior left bundle branch fibers; 3) the directly activated left ventricular zone was too small and relatively too late excited in respect of the right interventricular septum, from which the stimulus reached the left septum, to mask the LBBB electrocardiographic pattern; 4) in the presence of tachycardia-dependent LBBB the duration of left ventricular endocardial activation was about twice (62 msec) that found in the absence of tachycardia-dependent LBBB (28 msec).", "contents": "[The endocardial ventricular activation map in a case of intermittent BBS in phase III (author's transl)]. To obtain information on endocardial activation-sequence, unipolar recordings at seven left ventricular and six right ventricular points were performed in a 37-year-old man suffering from cardiomyopathy and tachycardia-dependent left bundle branch block (LBBB). Results were as follows: 1) the recovery time was longer in anterior than in posterior portion of left bundle branch fibers; 2) an high posterior left ventricular point was directly activated via posterior left bundle branch fibers; 3) the directly activated left ventricular zone was too small and relatively too late excited in respect of the right interventricular septum, from which the stimulus reached the left septum, to mask the LBBB electrocardiographic pattern; 4) in the presence of tachycardia-dependent LBBB the duration of left ventricular endocardial activation was about twice (62 msec) that found in the absence of tachycardia-dependent LBBB (28 msec)."} {"id": "PMID:157904", "title": "[The intra-operative proof of occlusion of the tubes in tubal sterilizations (author's transl)].", "content": "In tubal sterilization operations with a plastic clip failures with subsequent pregnancies become only known by misplacement of the clips. Failures are more frequent when the clips are placed through a posterior colpotomy. In 163 laparoscopic tubal sterilization with the Tuplar-clip during the last 2 1/2 years no subsequent pregnancy was observed. The carbon-dioxide pertubation or the chromo-pertubation after occlusion of the tubes with a clip permits an immediate intra-operative proof of secure bilateral tubal occlusion. A pregnancy due to faulty placement of the clip is then no longer possible. Other advantages of this method of tubal sterilization are mentioned.", "contents": "[The intra-operative proof of occlusion of the tubes in tubal sterilizations (author's transl)]. In tubal sterilization operations with a plastic clip failures with subsequent pregnancies become only known by misplacement of the clips. Failures are more frequent when the clips are placed through a posterior colpotomy. In 163 laparoscopic tubal sterilization with the Tuplar-clip during the last 2 1/2 years no subsequent pregnancy was observed. The carbon-dioxide pertubation or the chromo-pertubation after occlusion of the tubes with a clip permits an immediate intra-operative proof of secure bilateral tubal occlusion. A pregnancy due to faulty placement of the clip is then no longer possible. Other advantages of this method of tubal sterilization are mentioned."} {"id": "PMID:157905", "title": "[Lesion of the aorta abdominalis in gynecologic laparoscopy (author's transl)].", "content": "Two cases with lesions of abdominal aorta during gynecological laparoscopy are described. One case was fatal. The second patient could be saved from death. The misadventures occurred in diagnostic respectively operative laparoscopy.", "contents": "[Lesion of the aorta abdominalis in gynecologic laparoscopy (author's transl)]. Two cases with lesions of abdominal aorta during gynecological laparoscopy are described. One case was fatal. The second patient could be saved from death. The misadventures occurred in diagnostic respectively operative laparoscopy."} {"id": "PMID:157906", "title": "[Hybrid plasmid pSD1 containing the immunity region of bacteriophage lambda].", "content": "Hybrid plasmid pSD1 carrying the immunity region of the coliphage lambda and bio operon have been obtained by means of studying the efficiency of transcription DNA fragments in the plasmid RSF2124. The molecular weight of this plasmid is 17.2 Md. The growth inhibition of phage lambdavir has been observed in cells carrying the new hybrid plasma. The properties of the plasmid pSD1 and probable reasons of the growth inhibition of phage lambdavir are discussed. The hybrid plasmid pSD2 carrying genes R, A and J of phage lambda has been constructed on the basis of the plasmid RSF2124. There are cohesive ends in this plasmid which make possible its packing in the phage lambda head. Hybrid plasmid pSD3 carrying genes P and Q of phage lambda has also been constructed.", "contents": "[Hybrid plasmid pSD1 containing the immunity region of bacteriophage lambda]. Hybrid plasmid pSD1 carrying the immunity region of the coliphage lambda and bio operon have been obtained by means of studying the efficiency of transcription DNA fragments in the plasmid RSF2124. The molecular weight of this plasmid is 17.2 Md. The growth inhibition of phage lambdavir has been observed in cells carrying the new hybrid plasma. The properties of the plasmid pSD1 and probable reasons of the growth inhibition of phage lambdavir are discussed. The hybrid plasmid pSD2 carrying genes R, A and J of phage lambda has been constructed on the basis of the plasmid RSF2124. There are cohesive ends in this plasmid which make possible its packing in the phage lambda head. Hybrid plasmid pSD3 carrying genes P and Q of phage lambda has also been constructed."} {"id": "PMID:157907", "title": "[Inheritance of human fingerprints].", "content": "Polygenic threshold model of finger dermatoglyphics inheritance is worked out on the basis of family and population data. According to the model, ulnar loops are subthreshold patterns, which transforms into whorl or arch under the control of SU and SR gene complexes. Epistasis-hypostasis interactions take place between genes of SU and SR complexes. Classification of phenotypes for finger dermatoglyphics is offered and the frequency of these phenotypes in three populational samples of Kiev is studied.", "contents": "[Inheritance of human fingerprints]. Polygenic threshold model of finger dermatoglyphics inheritance is worked out on the basis of family and population data. According to the model, ulnar loops are subthreshold patterns, which transforms into whorl or arch under the control of SU and SR gene complexes. Epistasis-hypostasis interactions take place between genes of SU and SR complexes. Classification of phenotypes for finger dermatoglyphics is offered and the frequency of these phenotypes in three populational samples of Kiev is studied."} {"id": "PMID:157908", "title": "[Transposition of the deo operon structural genes in Escherichia coli K-12 to plasmid RP4 using bacteriophage mu].", "content": "Transposition of the structural genes of the deo operon of Escherichia coli K-12 into plasmid RP4 by means of temperate bacteriophage Mu was carried out. Some variants of composite RP4-deo-Mu plasmids were obtained and the expression of the deo genes integrated into the RP4 plasmid genome was studied. It was shown that the expression of these genes remains under the control of the chromosomal regulatory genes (deoR and cytR); although the activity of thymidine phosphorilase in the strain E. coli which contains hybrid plasmid is 4-6 fold greater than that in strains of E. coli with chromosomal localization of the deo operon.", "contents": "[Transposition of the deo operon structural genes in Escherichia coli K-12 to plasmid RP4 using bacteriophage mu]. Transposition of the structural genes of the deo operon of Escherichia coli K-12 into plasmid RP4 by means of temperate bacteriophage Mu was carried out. Some variants of composite RP4-deo-Mu plasmids were obtained and the expression of the deo genes integrated into the RP4 plasmid genome was studied. It was shown that the expression of these genes remains under the control of the chromosomal regulatory genes (deoR and cytR); although the activity of thymidine phosphorilase in the strain E. coli which contains hybrid plasmid is 4-6 fold greater than that in strains of E. coli with chromosomal localization of the deo operon."} {"id": "PMID:157909", "title": "[Population genetics of the population of the European north of the RSFSR. IV. The level of blood relationship in 5 villages of Pinega District, Archangel Province].", "content": "Computer program \"RODAN-1\" is used for inbreeding coefficient estimation. The population studied consists of two communities of 5 villages. 385 marriages were computed. The coefficient of inbreeding is 0.00145 for pedigree for rural Russian population (the Arkhangelsk region). The inverse dependence between a village size and corresponding data of inbreeding coefficient is suggested. An attempt was undertaken to estimate the genealogical information value for each pedigree and average information value for a village.", "contents": "[Population genetics of the population of the European north of the RSFSR. IV. The level of blood relationship in 5 villages of Pinega District, Archangel Province]. Computer program \"RODAN-1\" is used for inbreeding coefficient estimation. The population studied consists of two communities of 5 villages. 385 marriages were computed. The coefficient of inbreeding is 0.00145 for pedigree for rural Russian population (the Arkhangelsk region). The inverse dependence between a village size and corresponding data of inbreeding coefficient is suggested. An attempt was undertaken to estimate the genealogical information value for each pedigree and average information value for a village."} {"id": "PMID:157910", "title": "Construction and analysis of recombinant lambda phages containing mitochondrial DNA fragments.", "content": "Rat mtDNA has a molecular length of about 16 kilobase (kb) pairs and is cleaved into seven fragments by restriction endonuclease EcoRI. These fragments were cloned in Escherichia coli K-12 host using lambda gtWES.lambda B' (lambda gtWES.lambda B, for short, in this paper) as a vector. Recombinant DNAs containing one or a few fragments of the mtDNA were transfected to CaCl2-treated E. coli, and the plaques containing specific recombinant phages were selected. DNA amplified in the recombinanat phage lambda gt.mt was shown to contain the same restriction endonuclease cleavage sites as those found in the mtDNA. Present results permitted the DNA sequencing of any portion of the mitochondrial genome.", "contents": "Construction and analysis of recombinant lambda phages containing mitochondrial DNA fragments. Rat mtDNA has a molecular length of about 16 kilobase (kb) pairs and is cleaved into seven fragments by restriction endonuclease EcoRI. These fragments were cloned in Escherichia coli K-12 host using lambda gtWES.lambda B' (lambda gtWES.lambda B, for short, in this paper) as a vector. Recombinant DNAs containing one or a few fragments of the mtDNA were transfected to CaCl2-treated E. coli, and the plaques containing specific recombinant phages were selected. DNA amplified in the recombinanat phage lambda gt.mt was shown to contain the same restriction endonuclease cleavage sites as those found in the mtDNA. Present results permitted the DNA sequencing of any portion of the mitochondrial genome."} {"id": "PMID:157911", "title": "Inceptor and origin of DNA replication in lambdoid coliphages. I. The lambda DNA minimal replication system.", "content": "In a pBR313-lambda dv hybrid plasmid system, stepwise deletion and serial cloning procedures have led to a functional dissection of the DNA replication region of lambdoid bacteriophages lambda, 434 and 21. A simple system for initiation of DNA replication has been detected within lambdoid replicator DNAs, which is active in the absence of several normal replication elements, including the origin of replication (ori) and product of gene O. This \"minimal\" (or \"mini\") initiation system depends on the p0 or substitute leftward promoter in conjunction with the newly discovered \"inceptor\" (ice) element, which is located within the cII gene. Even the fragments containing ori are unable to initiate replication in these hybrid plasmids as long as fragments containing ice are missing. The base sequence of ice resembles transcriptional terminators and it appears to control both termination of primer RNA and inception of daughter strand DNA synthesis. Initiation in the p0-ice mini system of lambda or 21 phages requires the gene P product. Hwever, mini replication of 434 DNA hybrid plasmids required neither O nor P proteins, although there are only two single-base changes in the 434 inceptor sequence. The mini system is repressed by the elements of the maximal lambda replication system, as described in the accompanying publication.", "contents": "Inceptor and origin of DNA replication in lambdoid coliphages. I. The lambda DNA minimal replication system. In a pBR313-lambda dv hybrid plasmid system, stepwise deletion and serial cloning procedures have led to a functional dissection of the DNA replication region of lambdoid bacteriophages lambda, 434 and 21. A simple system for initiation of DNA replication has been detected within lambdoid replicator DNAs, which is active in the absence of several normal replication elements, including the origin of replication (ori) and product of gene O. This \"minimal\" (or \"mini\") initiation system depends on the p0 or substitute leftward promoter in conjunction with the newly discovered \"inceptor\" (ice) element, which is located within the cII gene. Even the fragments containing ori are unable to initiate replication in these hybrid plasmids as long as fragments containing ice are missing. The base sequence of ice resembles transcriptional terminators and it appears to control both termination of primer RNA and inception of daughter strand DNA synthesis. Initiation in the p0-ice mini system of lambda or 21 phages requires the gene P product. Hwever, mini replication of 434 DNA hybrid plasmids required neither O nor P proteins, although there are only two single-base changes in the 434 inceptor sequence. The mini system is repressed by the elements of the maximal lambda replication system, as described in the accompanying publication."} {"id": "PMID:157912", "title": "Inceptor and origin of DNA replication in lambdoid coliphages. II. The lambda DNA maximal replication system.", "content": "In pBR313-lambda dv hydrid plasmids a second system for initiation of DNA replication has been detected in lambdoid replicator DNAs (in the absence of the p0 promoter). The \"maximal\" (or \"maxi\") initiation system depends on the origin of replication (ori) sequence, in conjuction with the \"inceptor\" (ice) element located in the lambdoid cII genes. Only leftward, but not bidirectional, primer RNA synthesis seems to be initiated at ori in its newly defined boundaries, and it appears to be catalysed by dnaG-coded primase. Only if transcriptionally activated, will ori effectively initiate lambda specific, O and P-dependent \"maximal\" hybrid-plasmid replication. In addition, it will repress a complete lambda \"minimal\" initiation system in cis, i.e., if present on the same plasmid molecule. This newly discovered repressive activity of the ori system depends on only three factors: an intact left section of ori, the O product, and transcriptional activation of ori (rightward or leftward). A repressed minimal initiation system will regain its activity as soon as a segment carrying either part of the O gene or a promoter for transcriptional activation is delected from such a plasmid which was combining both the \"mini\" and \"maxi\" systems of lambda replication.", "contents": "Inceptor and origin of DNA replication in lambdoid coliphages. II. The lambda DNA maximal replication system. In pBR313-lambda dv hydrid plasmids a second system for initiation of DNA replication has been detected in lambdoid replicator DNAs (in the absence of the p0 promoter). The \"maximal\" (or \"maxi\") initiation system depends on the origin of replication (ori) sequence, in conjuction with the \"inceptor\" (ice) element located in the lambdoid cII genes. Only leftward, but not bidirectional, primer RNA synthesis seems to be initiated at ori in its newly defined boundaries, and it appears to be catalysed by dnaG-coded primase. Only if transcriptionally activated, will ori effectively initiate lambda specific, O and P-dependent \"maximal\" hybrid-plasmid replication. In addition, it will repress a complete lambda \"minimal\" initiation system in cis, i.e., if present on the same plasmid molecule. This newly discovered repressive activity of the ori system depends on only three factors: an intact left section of ori, the O product, and transcriptional activation of ori (rightward or leftward). A repressed minimal initiation system will regain its activity as soon as a segment carrying either part of the O gene or a promoter for transcriptional activation is delected from such a plasmid which was combining both the \"mini\" and \"maxi\" systems of lambda replication."} {"id": "PMID:157914", "title": "Atypical leukodystrophy with accumulations of sulfatide and mucopolysaccharide.", "content": "1. Follow-up studies of two siblings with mental retardation, progressive paraplegia and dementia were reported. 2. The brain and visceral organs of a patient (elder brother) who died recently were investigated histopathologically, electronmicroscopically and neurochemically. a. Moderate, diffuse demyelination occurred throughout the white matter of the central nervous system. b. Two abnormal materials were deposited in the white matter: one showed metachromasia containing sulfatide and another had staining characteristics of acid mucopolysaccharide histochemically. Electronmicroscopically, the former was a conglomerate of electron-dense materials of various degrees and the latter had a membrane-limited granular structure. The myocardium contained the same mucopolysaccharide material as that in the brain. c. Slight increase of sulfatide was found in the cerebral white matter. Arylsulfatase A activities were preserved in the brain as well as in the liver. Contents of hexosamine and uronic acid in the white matter were about three or five times as much as that of the controls. Electrophoresis on cellulose acetate membrane showed that acid glucopeptide was the main component of the mucopolysaccharide extracted from the brain.", "contents": "Atypical leukodystrophy with accumulations of sulfatide and mucopolysaccharide. 1. Follow-up studies of two siblings with mental retardation, progressive paraplegia and dementia were reported. 2. The brain and visceral organs of a patient (elder brother) who died recently were investigated histopathologically, electronmicroscopically and neurochemically. a. Moderate, diffuse demyelination occurred throughout the white matter of the central nervous system. b. Two abnormal materials were deposited in the white matter: one showed metachromasia containing sulfatide and another had staining characteristics of acid mucopolysaccharide histochemically. Electronmicroscopically, the former was a conglomerate of electron-dense materials of various degrees and the latter had a membrane-limited granular structure. The myocardium contained the same mucopolysaccharide material as that in the brain. c. Slight increase of sulfatide was found in the cerebral white matter. Arylsulfatase A activities were preserved in the brain as well as in the liver. Contents of hexosamine and uronic acid in the white matter were about three or five times as much as that of the controls. Electrophoresis on cellulose acetate membrane showed that acid glucopeptide was the main component of the mucopolysaccharide extracted from the brain."} {"id": "PMID:157915", "title": "[Predictive diagnostic value of renal blood flow measurement in renovascular hypertension (author's transl)].", "content": "To improve diagnostic procedures and preoperative prognosis in hypertensive patients with angiographically proven renal artery stenosis pre- and postoperative studies of renal hemodynamics (133xenon washout technique) were carried out in patients with normalized, improved and unchanged hypertensive blood pressure values following renovascular surgery. The results demonstrate that renal blood flow in both the operated and non-stenosed kidneys has to be in a normal range expecting a normalization of blood pressure. The existence of a preoperative normal cortical flow rate in the stenosed kidney may be a hint to a normalization of hemodynamic of the involved kidney following reconstructive surgery.", "contents": "[Predictive diagnostic value of renal blood flow measurement in renovascular hypertension (author's transl)]. To improve diagnostic procedures and preoperative prognosis in hypertensive patients with angiographically proven renal artery stenosis pre- and postoperative studies of renal hemodynamics (133xenon washout technique) were carried out in patients with normalized, improved and unchanged hypertensive blood pressure values following renovascular surgery. The results demonstrate that renal blood flow in both the operated and non-stenosed kidneys has to be in a normal range expecting a normalization of blood pressure. The existence of a preoperative normal cortical flow rate in the stenosed kidney may be a hint to a normalization of hemodynamic of the involved kidney following reconstructive surgery."} {"id": "PMID:157925", "title": "[Long-term follow-up after spontaneous contrast extravasation during infusion urograms (author's transl)].", "content": "In 1978 we described 18 patients with acute spontaneous rupture of a pelvi-calycine system; these have now been followed up with the exception of four patients. The aim was to determine whether, and how frequently, long-term complications occur, such as chronic persistent rupture and particularly whether local retroperitoneal fibrosis develops. The clinical history, infusion urograms and cinematography provided no evidence of any abnormalities except in one case. In this patient changes interpreted as retroperitoneal fibrosis were found, but this was the only patient in whom surgery had been performed. It is thought that the operation played a significant part in the development of this complication. Our observations confirm that infusion urograms in acute urinary tract obstruction are an acceptable method of investigation and that extravasation should be treated conservatively. The exception to this rule is the presence of preexisting infection of the urinary tract.", "contents": "[Long-term follow-up after spontaneous contrast extravasation during infusion urograms (author's transl)]. In 1978 we described 18 patients with acute spontaneous rupture of a pelvi-calycine system; these have now been followed up with the exception of four patients. The aim was to determine whether, and how frequently, long-term complications occur, such as chronic persistent rupture and particularly whether local retroperitoneal fibrosis develops. The clinical history, infusion urograms and cinematography provided no evidence of any abnormalities except in one case. In this patient changes interpreted as retroperitoneal fibrosis were found, but this was the only patient in whom surgery had been performed. It is thought that the operation played a significant part in the development of this complication. Our observations confirm that infusion urograms in acute urinary tract obstruction are an acceptable method of investigation and that extravasation should be treated conservatively. The exception to this rule is the presence of preexisting infection of the urinary tract."} {"id": "PMID:157926", "title": "[The treatment of idiopathic varicocoeles by transfemoral spiral occlusion of the left testicular vein (author's transl)].", "content": "The standard surgical procedures for the treatment of idiopathic varicocoeles are unsuccessful in, or show a recurrence rate of, up to 25%. An alternative method is transcutaneous embolisation using the Seldinger catheter technique. For this technique of transcutaneous catheter embolization, we have used the Gianturco spiral. The embolization is carried out following diagnostic transfemoral phlebography of the left testicular vein, which also provides the indications or contra-indications for this procedure. The method has been used on nineteen patients with varicocoeles requiring treatment; amonst these were three patients who had had unsuccessful operations. Follow-up period so far is six months. In all cases the varicocoele had disappeared, including one patient who had suffered complications following previous surgery.", "contents": "[The treatment of idiopathic varicocoeles by transfemoral spiral occlusion of the left testicular vein (author's transl)]. The standard surgical procedures for the treatment of idiopathic varicocoeles are unsuccessful in, or show a recurrence rate of, up to 25%. An alternative method is transcutaneous embolisation using the Seldinger catheter technique. For this technique of transcutaneous catheter embolization, we have used the Gianturco spiral. The embolization is carried out following diagnostic transfemoral phlebography of the left testicular vein, which also provides the indications or contra-indications for this procedure. The method has been used on nineteen patients with varicocoeles requiring treatment; amonst these were three patients who had had unsuccessful operations. Follow-up period so far is six months. In all cases the varicocoele had disappeared, including one patient who had suffered complications following previous surgery."} {"id": "PMID:157927", "title": "[Grey-scale ultrasound in the diagnosis of cystic lesions of the kidney (comparison with excretory urography) (author's transl)].", "content": "In a total of 155 cystic renal lesions diagnozed by means of ultrasound the correct differentiation of cystic or solid consistency could be determined in 96.8% of cases. The sonographic result was inaccurate or false in only 2.6%. Sonography also determined the correct morphological and anatomical type of the liquid space-occupying formation in 89%. Pathological cavities of the renal pelvis as well as hydronephroses were the cause of incorrect diagnoses. 36.6% of solitary renal cysts revealed by ultrasound (average diameter of cyst: 3.9 cm), could not be detected by pyelography; radiology most frequently failed to determine cortical renal cysts. Sensitivity and specificity of nephrosonography for detection of cystic malformation of the kidney were distinctly better than pyelography. Out of a total of 34 patients with hereditary polycystic renal disease (HRPD) sonography diagnozed multiple cysts of the liver in 15 cases (44%). The use of ultrasound in examining relatives of patients with HPRD enables an earlier diagnosis of the chronic progressive disease.", "contents": "[Grey-scale ultrasound in the diagnosis of cystic lesions of the kidney (comparison with excretory urography) (author's transl)]. In a total of 155 cystic renal lesions diagnozed by means of ultrasound the correct differentiation of cystic or solid consistency could be determined in 96.8% of cases. The sonographic result was inaccurate or false in only 2.6%. Sonography also determined the correct morphological and anatomical type of the liquid space-occupying formation in 89%. Pathological cavities of the renal pelvis as well as hydronephroses were the cause of incorrect diagnoses. 36.6% of solitary renal cysts revealed by ultrasound (average diameter of cyst: 3.9 cm), could not be detected by pyelography; radiology most frequently failed to determine cortical renal cysts. Sensitivity and specificity of nephrosonography for detection of cystic malformation of the kidney were distinctly better than pyelography. Out of a total of 34 patients with hereditary polycystic renal disease (HRPD) sonography diagnozed multiple cysts of the liver in 15 cases (44%). The use of ultrasound in examining relatives of patients with HPRD enables an earlier diagnosis of the chronic progressive disease."} {"id": "PMID:157928", "title": "[Sonographic findings in blunt renal trauma (author's transl)].", "content": "The kidneys are beautiful organs for ultrasonography, because of their position, well defined characteristic appearance and excellent acoustic qualities. This is highly important for assessing all pathologies leading to macromorphological changes of the kidneys including these in blunt renal trauma. We could'nt find any paper on this topic in the recent literature available for us. Our own material in renal blunt trauma includes 17 patients. There were no pathological findings in 7, and pathological findings in 10 of them. Sonographic accuracy in severe trauma of the kidney is about 100%, excluding hydronephrotic kidneys, which cannot always be distinguished from a bigger parapelvic cyst. Urogramm resp. Uronephrotomogramm should be performed and studied thoroughly. Exceptions are Iodine allergy and pregnancy.", "contents": "[Sonographic findings in blunt renal trauma (author's transl)]. The kidneys are beautiful organs for ultrasonography, because of their position, well defined characteristic appearance and excellent acoustic qualities. This is highly important for assessing all pathologies leading to macromorphological changes of the kidneys including these in blunt renal trauma. We could'nt find any paper on this topic in the recent literature available for us. Our own material in renal blunt trauma includes 17 patients. There were no pathological findings in 7, and pathological findings in 10 of them. Sonographic accuracy in severe trauma of the kidney is about 100%, excluding hydronephrotic kidneys, which cannot always be distinguished from a bigger parapelvic cyst. Urogramm resp. Uronephrotomogramm should be performed and studied thoroughly. Exceptions are Iodine allergy and pregnancy."} {"id": "PMID:157929", "title": "[The value of the excretion urogram following cerebral angiography (author's transl)].", "content": "Routine abdominal films were obtained after 100 carotid angiograms in order to see the excretion urogram. In 64 patients the contrast was adequate for diagnosis. In twelve of these a significant finding was observed. This simple additional examination was particularly valuable in searching for a primary tumour when the angiogram had demonstrated cerebral metastases.", "contents": "[The value of the excretion urogram following cerebral angiography (author's transl)]. Routine abdominal films were obtained after 100 carotid angiograms in order to see the excretion urogram. In 64 patients the contrast was adequate for diagnosis. In twelve of these a significant finding was observed. This simple additional examination was particularly valuable in searching for a primary tumour when the angiogram had demonstrated cerebral metastases."} {"id": "PMID:157930", "title": "Barium enema in pediatric intussusception; a review of 108 cases.", "content": "A material of 108 patients with 125 intussusceptions was evaluated retrospectively. Barium enema is recommended as an excellent diagnostic tool. Reduction should be tried in all cases except those with signs of peritonitis, because the enema causes fewer complications and leads to a considerably decreased hospital stay.", "contents": "Barium enema in pediatric intussusception; a review of 108 cases. A material of 108 patients with 125 intussusceptions was evaluated retrospectively. Barium enema is recommended as an excellent diagnostic tool. Reduction should be tried in all cases except those with signs of peritonitis, because the enema causes fewer complications and leads to a considerably decreased hospital stay."} {"id": "PMID:157931", "title": "[Double colon--a rare case of intestinal duplication (author's transl)].", "content": "A case of duplication of the entire colon, in which the supernumerary colon had no communication with the small intestine, is presented and illustrated. After review of the literature the special clinical and radiologic problems of these intestinal duplications are discussed.", "contents": "[Double colon--a rare case of intestinal duplication (author's transl)]. A case of duplication of the entire colon, in which the supernumerary colon had no communication with the small intestine, is presented and illustrated. After review of the literature the special clinical and radiologic problems of these intestinal duplications are discussed."} {"id": "PMID:157932", "title": "[Retropneumoperitoneum and pneumomediastinum following proctoscopy (author's transl)].", "content": "A 66-year-old patient developed a retropneumoperitoneum and pneumomediastinum after a proctoscopy. Following the examination, which was done as an out patient, he had some pain but was able to reach home without difficulty. Radiography of the abdomen on the next day showed definite gas collection round the right kidney and below the middle of the diaphragm. The mediastinum showed some translucencies consistent with cranial spread of air from the retropneumoperitoneum; it was particularly marked round the aorta. The film also showed supraclavicular emphysema. After being placed supine the patient's symptoms rapidly disappeared. There were no complications and no treatment was necessary. The case is discussed in relation to the relevant literature.", "contents": "[Retropneumoperitoneum and pneumomediastinum following proctoscopy (author's transl)]. A 66-year-old patient developed a retropneumoperitoneum and pneumomediastinum after a proctoscopy. Following the examination, which was done as an out patient, he had some pain but was able to reach home without difficulty. Radiography of the abdomen on the next day showed definite gas collection round the right kidney and below the middle of the diaphragm. The mediastinum showed some translucencies consistent with cranial spread of air from the retropneumoperitoneum; it was particularly marked round the aorta. The film also showed supraclavicular emphysema. After being placed supine the patient's symptoms rapidly disappeared. There were no complications and no treatment was necessary. The case is discussed in relation to the relevant literature."} {"id": "PMID:157933", "title": "[Arthrosis of the distal radio-ulnar joint in workers using motorised saws (author's transl)].", "content": "Vibration-induced changes in the distal radio-ulnar joint were analysed by comparing workers using motorised saws (978 cases) and a control group. The following are the essential findings: 1. Exposure to vibration causes characteristic changes in the distal radio-ulnar joint, particularly on the left, consisting of osteophytosis, deformity and cystic rarefaction. 2. The frequency of the arthrosis is related in a statistically significant manner to a) length of exposure, b) age. 3. The subjective complaints of numbness, weakness and pain can, to some extent, be related to the radio-ulnar arthrosis. 4. Vibration is not the only factor in the genesis of the degenerative process of the distal radio-ulnar joint; ordinary use and stress can cause similar changes, although to a much less marked extent. The aetiological role of local vibration as a factor in causing the arthrosis has been confirmed.", "contents": "[Arthrosis of the distal radio-ulnar joint in workers using motorised saws (author's transl)]. Vibration-induced changes in the distal radio-ulnar joint were analysed by comparing workers using motorised saws (978 cases) and a control group. The following are the essential findings: 1. Exposure to vibration causes characteristic changes in the distal radio-ulnar joint, particularly on the left, consisting of osteophytosis, deformity and cystic rarefaction. 2. The frequency of the arthrosis is related in a statistically significant manner to a) length of exposure, b) age. 3. The subjective complaints of numbness, weakness and pain can, to some extent, be related to the radio-ulnar arthrosis. 4. Vibration is not the only factor in the genesis of the degenerative process of the distal radio-ulnar joint; ordinary use and stress can cause similar changes, although to a much less marked extent. The aetiological role of local vibration as a factor in causing the arthrosis has been confirmed."} {"id": "PMID:157934", "title": "[Lymphangiomatosis of bone in childhood (author's transl)].", "content": "Lymphangiomatosis of bone is a very rare congenital malformation of lymph vessels. So far 60 patients have been described with this disease (43 children, 17 adults). Radiologically the lymphangiomatous skeletal changes usually consist of circumscribed areas of uni- or multi-focal osteolysis. They may remain asymptomatic for years; in a few cases intrathoracic chylous effusions or pathological fractures have occurred. The protean radiological appearances of bone lymphangiomatosis are illustrated by four children. The differential diagnosis is discussed in detail.", "contents": "[Lymphangiomatosis of bone in childhood (author's transl)]. Lymphangiomatosis of bone is a very rare congenital malformation of lymph vessels. So far 60 patients have been described with this disease (43 children, 17 adults). Radiologically the lymphangiomatous skeletal changes usually consist of circumscribed areas of uni- or multi-focal osteolysis. They may remain asymptomatic for years; in a few cases intrathoracic chylous effusions or pathological fractures have occurred. The protean radiological appearances of bone lymphangiomatosis are illustrated by four children. The differential diagnosis is discussed in detail."} {"id": "PMID:157935", "title": "[Extensive, diffuse haemangiomatosis of the skeleton (author's transl)].", "content": "The roentgenological appearance and the clinical course of a case of diffuse skeletal haemangiomatosis are described. Megavoltage radiotherapy was given to several areas involved, including parts of the vertebral column; the treatment led to an improvement of bone pain and of neurological symptoms caused by cord compression. The differential diagnosis and the suggestion of Karlin and Brower (1977) to make a distinction between \"multiple primary hemangiomas\" and \"diffuse cystic angiomatosis\" of bone are discussed.", "contents": "[Extensive, diffuse haemangiomatosis of the skeleton (author's transl)]. The roentgenological appearance and the clinical course of a case of diffuse skeletal haemangiomatosis are described. Megavoltage radiotherapy was given to several areas involved, including parts of the vertebral column; the treatment led to an improvement of bone pain and of neurological symptoms caused by cord compression. The differential diagnosis and the suggestion of Karlin and Brower (1977) to make a distinction between \"multiple primary hemangiomas\" and \"diffuse cystic angiomatosis\" of bone are discussed."} {"id": "PMID:157936", "title": "[Osteogenesis imperfecta cystica (Fairbank)--a special form of osteogenesis imperfecta congenita (Vrolik) (author's transl)].", "content": "Two patients, aged 13 and 19 years, with osteogenesis imperfecta congenita (Vrolik) have been seen at the rehabilitation centre at Neckargemund. The younger patient showed the typical appearances of osteogenesis imperfecta cystica (Fairbank), while the older patient failed to show these changes in the skeleton. Contrary to the frequently expressed view that patients with osteogenesis imperfecta congenita always die in the perinatal period, they may survive for a considerable length of time. The change of osteogenesis imperfecta congenita (Vrolik) into osteogensis imperfecta cystica (Fairbank) has been described as a sequence in the occasional survivors by Spranger, but is not a necessary condition for survival. Osteogenesis imperfecta cystica should be regarded as an extremely rare special type of Vrolik's disease.", "contents": "[Osteogenesis imperfecta cystica (Fairbank)--a special form of osteogenesis imperfecta congenita (Vrolik) (author's transl)]. Two patients, aged 13 and 19 years, with osteogenesis imperfecta congenita (Vrolik) have been seen at the rehabilitation centre at Neckargemund. The younger patient showed the typical appearances of osteogenesis imperfecta cystica (Fairbank), while the older patient failed to show these changes in the skeleton. Contrary to the frequently expressed view that patients with osteogenesis imperfecta congenita always die in the perinatal period, they may survive for a considerable length of time. The change of osteogenesis imperfecta congenita (Vrolik) into osteogensis imperfecta cystica (Fairbank) has been described as a sequence in the occasional survivors by Spranger, but is not a necessary condition for survival. Osteogenesis imperfecta cystica should be regarded as an extremely rare special type of Vrolik's disease."} {"id": "PMID:157937", "title": "[Image quality in medium format film technique (fluorography) (author's transl)].", "content": "The paper deals with image quality of films using a medium format type film and fluorography. Contrast transmission function is achieved by special calcium tungstate screens. In practice, image quality equals that of full size films with universal screens. By increasing lens size it is possible to reduce the necessary x-ray dose without losing image quality.", "contents": "[Image quality in medium format film technique (fluorography) (author's transl)]. The paper deals with image quality of films using a medium format type film and fluorography. Contrast transmission function is achieved by special calcium tungstate screens. In practice, image quality equals that of full size films with universal screens. By increasing lens size it is possible to reduce the necessary x-ray dose without losing image quality."} {"id": "PMID:157938", "title": "[Evaluation of the somatic radiation risks and the recommendations in the IRCP publication no. 26 (1977) (author's transl)].", "content": "Scientific knowledge regarding somatic radiation risks has greatly increased in recent years as a result of a series of epidemiological studies. IRCP publication no. 26 concerns largely to a collection of data published in a report of the United Nations in 1977. For weakly ionising radiation, both publications introduce a risk factor representing the risk per rem for small doses. As a result, they introduced a reduction factor for the risks from ionising radiation at small doses. An analysis of the data of the most common radiation induced cancers has shown that their estimates are not on the side of safety. It is concluded that the doses regarded as acceptable by the IRCP are too high for persons exposed to radiation in the course of their profession.", "contents": "[Evaluation of the somatic radiation risks and the recommendations in the IRCP publication no. 26 (1977) (author's transl)]. Scientific knowledge regarding somatic radiation risks has greatly increased in recent years as a result of a series of epidemiological studies. IRCP publication no. 26 concerns largely to a collection of data published in a report of the United Nations in 1977. For weakly ionising radiation, both publications introduce a risk factor representing the risk per rem for small doses. As a result, they introduced a reduction factor for the risks from ionising radiation at small doses. An analysis of the data of the most common radiation induced cancers has shown that their estimates are not on the side of safety. It is concluded that the doses regarded as acceptable by the IRCP are too high for persons exposed to radiation in the course of their profession."} {"id": "PMID:157939", "title": "[Considerations regarding the differential diagnosis during the angiography of non-functioning kidneys (author's transl)].", "content": "Utilizing selective renal arteriograms and phlebograms in 7 patients, the differential diagnostic difficulties in separating poorly vascularized tumors from inflammatory lesions are discussed. Retrograde studies either offered no help, or could technically not be accomplished; arteriography proved equivocal in most cases. However, renal phlebography was found to be quite helpful, in that a non-visualized or reduced opacification of the intrarenal venous system, along with irregular extrinsic venous impressions, spoke more for a malignant tumor. When the contrast was able to fill the veins out to the periphery, a tumor could with great certainty be ruled out. Severe inflammatory conditions, while demonstrating a generalized reduction in the opacification of the venous system, did not show the bizarre venous wall irregularities seen with tumors. Retroperitoneal fibrosis and its special diagnostic difficulties are discussed.", "contents": "[Considerations regarding the differential diagnosis during the angiography of non-functioning kidneys (author's transl)]. Utilizing selective renal arteriograms and phlebograms in 7 patients, the differential diagnostic difficulties in separating poorly vascularized tumors from inflammatory lesions are discussed. Retrograde studies either offered no help, or could technically not be accomplished; arteriography proved equivocal in most cases. However, renal phlebography was found to be quite helpful, in that a non-visualized or reduced opacification of the intrarenal venous system, along with irregular extrinsic venous impressions, spoke more for a malignant tumor. When the contrast was able to fill the veins out to the periphery, a tumor could with great certainty be ruled out. Severe inflammatory conditions, while demonstrating a generalized reduction in the opacification of the venous system, did not show the bizarre venous wall irregularities seen with tumors. Retroperitoneal fibrosis and its special diagnostic difficulties are discussed."} {"id": "PMID:157940", "title": "[Spinal irritation after myelography with Amipaque in patients with kyphoscoliosis (author's transl)].", "content": "Two patients with severe kyphoscoliosis developed marked spinal irritation following myelography with the new non-ionising contrast medium Amipaque. The authors raise the possibility that the spinal deformity may result in reduced flow of cerebro-spinal fluid; this may prolong the contact of the contrast medium with the (previously damaged?) spinal cord. Patients with this type of spinal deformity require particularly stringent indications for the performance of myelography, even when using Amipaque.", "contents": "[Spinal irritation after myelography with Amipaque in patients with kyphoscoliosis (author's transl)]. Two patients with severe kyphoscoliosis developed marked spinal irritation following myelography with the new non-ionising contrast medium Amipaque. The authors raise the possibility that the spinal deformity may result in reduced flow of cerebro-spinal fluid; this may prolong the contact of the contrast medium with the (previously damaged?) spinal cord. Patients with this type of spinal deformity require particularly stringent indications for the performance of myelography, even when using Amipaque."} {"id": "PMID:157941", "title": "Postirradiation changes on the lymphatics studied by lymphography.", "content": "Repeat lymphography was done in 33 patients following radiotherapy between 8--73 months. Absorbed dose delivered by 60Co-teletherapy ranged between 30--45 Gy-s in subdiaphragmatic and 30,6--56 Gy-s in mediastinal region. The main sequel of radiation was decrease in nodal size (66,6%), lumen narrowing of lymphatic vessels (51,5%); number of lymph nodes and lymph vessels diminished rarely (6%). Blocking of lymph circulation never developed. Dilatation of thoracic duct with accelerated contrast flow rate was thought to be arteficial due to decreased pooling capacity of decreased nodal size. Radiation induced changes develop within 12 months and do not progress further on. It is concluded that changes are mainly affected by the level of absorbed dose.", "contents": "Postirradiation changes on the lymphatics studied by lymphography. Repeat lymphography was done in 33 patients following radiotherapy between 8--73 months. Absorbed dose delivered by 60Co-teletherapy ranged between 30--45 Gy-s in subdiaphragmatic and 30,6--56 Gy-s in mediastinal region. The main sequel of radiation was decrease in nodal size (66,6%), lumen narrowing of lymphatic vessels (51,5%); number of lymph nodes and lymph vessels diminished rarely (6%). Blocking of lymph circulation never developed. Dilatation of thoracic duct with accelerated contrast flow rate was thought to be arteficial due to decreased pooling capacity of decreased nodal size. Radiation induced changes develop within 12 months and do not progress further on. It is concluded that changes are mainly affected by the level of absorbed dose."} {"id": "PMID:157946", "title": "[Radiologic investigations following abdomino-perineal resection of the rectum (author's transl)].", "content": "After abdominoperineal resection of the rectum specific alterations due to operation and disease can be distinguished. In over eighty percent the ureters and the urinary bladder are concerned. The topography of the small-intestine in the sacral cavity reveals alterations of the pelvic floor which generally are local recurrences of carcinoma. In both examinations special importance has to be laid on a lateral view of the pelvis. Indications and results of supplementary examinations are discussed. Computed tomography will deliver additional informations for the diagnosis of recurrent carcinoma; the value of CT is checked at the moment. Considering the amount and importance of treatable illness following resection of the rectum a standardized program for examination seems inevitable. Our experience with over 400 cases is, that this program can reveal important informations for postoperative care which up to now has often been underestimated, even from a radiologic point of view.", "contents": "[Radiologic investigations following abdomino-perineal resection of the rectum (author's transl)]. After abdominoperineal resection of the rectum specific alterations due to operation and disease can be distinguished. In over eighty percent the ureters and the urinary bladder are concerned. The topography of the small-intestine in the sacral cavity reveals alterations of the pelvic floor which generally are local recurrences of carcinoma. In both examinations special importance has to be laid on a lateral view of the pelvis. Indications and results of supplementary examinations are discussed. Computed tomography will deliver additional informations for the diagnosis of recurrent carcinoma; the value of CT is checked at the moment. Considering the amount and importance of treatable illness following resection of the rectum a standardized program for examination seems inevitable. Our experience with over 400 cases is, that this program can reveal important informations for postoperative care which up to now has often been underestimated, even from a radiologic point of view."} {"id": "PMID:157947", "title": "[Computer tomographic findings after resection of the rectum (author's transl)].", "content": "Computed tomography findings in the pelvis after resection of the rectum, obtained from 48 patients primarily suspected of recurrent carcinoma, are represented. Compared with conventional radiographic methods CT demonstrates directly in most cases the presence of a pelvic mass, its extension and relationship to adjacent soft tissue. In some cases this is advantageous for further diagnostic procedures, but also for treatment and further check-up. False conclusions are discussed. The distinction between recurrent carcinoma and retroperitoneal fibrosis in the pelvis, frequently enhanced by retarded healing of the sacral cavity, remains a problem. Progress in the early diagnosis of recurrence of pelvic mass could be made by regular CT check-up during the first two years after resection of the rectum, to increase the value of palliative radiotherapy treatment indicated in any case. As CT, however, is expensive and not always available, this demand cannot be met and the value of conventional radiographic methods remains at present unquestioned.", "contents": "[Computer tomographic findings after resection of the rectum (author's transl)]. Computed tomography findings in the pelvis after resection of the rectum, obtained from 48 patients primarily suspected of recurrent carcinoma, are represented. Compared with conventional radiographic methods CT demonstrates directly in most cases the presence of a pelvic mass, its extension and relationship to adjacent soft tissue. In some cases this is advantageous for further diagnostic procedures, but also for treatment and further check-up. False conclusions are discussed. The distinction between recurrent carcinoma and retroperitoneal fibrosis in the pelvis, frequently enhanced by retarded healing of the sacral cavity, remains a problem. Progress in the early diagnosis of recurrence of pelvic mass could be made by regular CT check-up during the first two years after resection of the rectum, to increase the value of palliative radiotherapy treatment indicated in any case. As CT, however, is expensive and not always available, this demand cannot be met and the value of conventional radiographic methods remains at present unquestioned."} {"id": "PMID:157948", "title": "[Angiographic features of liver echinococcosis (author's transl)].", "content": "From 1973 to 1978 13 cases of cystic hydatid disease and 15 cases of alveolar hydatid disease of the liver were diagnosed by angiography. The main diagnostic features of cystic hydatid disease of the liver are the following: \"rim-sign\", avascular areas, curved displacement of the arteries and stretching of the intrahepatic arteries. Multilocular hydatid disease of the liver shows tumor-like angiographic signs, such as atypical vascular formations, distensions, vascular irregularities, arterial stenoses as well as hepatosplenomegaly. Differential diagnosis in malignant liver diseases is often impossible, but early venous filling and arteriovenous shunts are not characteristic of multilocular hydatid disease of the liver. Particularly difficult is the interpretation in patients who have had previous surgery.", "contents": "[Angiographic features of liver echinococcosis (author's transl)]. From 1973 to 1978 13 cases of cystic hydatid disease and 15 cases of alveolar hydatid disease of the liver were diagnosed by angiography. The main diagnostic features of cystic hydatid disease of the liver are the following: \"rim-sign\", avascular areas, curved displacement of the arteries and stretching of the intrahepatic arteries. Multilocular hydatid disease of the liver shows tumor-like angiographic signs, such as atypical vascular formations, distensions, vascular irregularities, arterial stenoses as well as hepatosplenomegaly. Differential diagnosis in malignant liver diseases is often impossible, but early venous filling and arteriovenous shunts are not characteristic of multilocular hydatid disease of the liver. Particularly difficult is the interpretation in patients who have had previous surgery."} {"id": "PMID:157949", "title": "[Improved radiological diagnosis in the stomach by means of an improved contrast material (author's transl)].", "content": "Our experience with a cheap contrast medium, which we prepare ourselves, is described, stretching over a period of 18 months. It is based on the bubbly barium first described by Op den Orth and is made by means of carbon dioxide in a soda water syphon. It is better for detailed contrast examination of the stomach than the commercially available contrast media. It is thought that this is due to optimal viscosity for wetting of the mucosa, optimal size of the barium sulphate particles, which are larger than one micron, and greater distension of the stomach due to greater quantities of CO2. The use of bubbly barium for routine examination of the stomach, using double contrast and hypotonia with graded compression, almost always results in demonstration of the areae gastricae in large parts of the stomach. We regard this as a sign of a good examination, since we are then able to demonstrate small lesions such as complete or incomplete erosions, ulcer scars or flat ulcers.", "contents": "[Improved radiological diagnosis in the stomach by means of an improved contrast material (author's transl)]. Our experience with a cheap contrast medium, which we prepare ourselves, is described, stretching over a period of 18 months. It is based on the bubbly barium first described by Op den Orth and is made by means of carbon dioxide in a soda water syphon. It is better for detailed contrast examination of the stomach than the commercially available contrast media. It is thought that this is due to optimal viscosity for wetting of the mucosa, optimal size of the barium sulphate particles, which are larger than one micron, and greater distension of the stomach due to greater quantities of CO2. The use of bubbly barium for routine examination of the stomach, using double contrast and hypotonia with graded compression, almost always results in demonstration of the areae gastricae in large parts of the stomach. We regard this as a sign of a good examination, since we are then able to demonstrate small lesions such as complete or incomplete erosions, ulcer scars or flat ulcers."} {"id": "PMID:157950", "title": "[Crohn's disease of the colon (author's transl)].", "content": "Despite the availability of endoscopy, radiological examination remains an essential method in the investigation of Crohn's disease. Various authors agree that it has an accuracy of 75% (1, 8, 14, 20). In our experience accuracy is somewhere between 70 and 85%. These figures depend on the fact that in about 16% histology is also unable to make a definite diagnosis. Crohn's disease of the large bowel is of significance since it is often misinterpreted as ulcerative colitis, because in 10% of cases there is no involvement of the terminal ileum. The final diagnosis depends on the summation of the individual features whose individual significance must be considered. Malignant involvement of the peritoneum, which has not been extensively described in the radiological literature, may result in changes in the wall of the colon and lead to an appearance resembling Crohn's disease, with consequent errors in diagnosis.", "contents": "[Crohn's disease of the colon (author's transl)]. Despite the availability of endoscopy, radiological examination remains an essential method in the investigation of Crohn's disease. Various authors agree that it has an accuracy of 75% (1, 8, 14, 20). In our experience accuracy is somewhere between 70 and 85%. These figures depend on the fact that in about 16% histology is also unable to make a definite diagnosis. Crohn's disease of the large bowel is of significance since it is often misinterpreted as ulcerative colitis, because in 10% of cases there is no involvement of the terminal ileum. The final diagnosis depends on the summation of the individual features whose individual significance must be considered. Malignant involvement of the peritoneum, which has not been extensively described in the radiological literature, may result in changes in the wall of the colon and lead to an appearance resembling Crohn's disease, with consequent errors in diagnosis."} {"id": "PMID:157951", "title": "[Computer tomographic diagnosis of pericardial effusions (author's transl)].", "content": "Thirty patients with suspected pericardial effusions, or with cardiac enlargement of unknown cause were examined by computer tomography. In 19 cases a diagnosis of pericardial effusion or haematoma was made. All these cases were confirmed by echo cardiography or transthoracic puncture. The accuracy of computer tomography diagnosis did not depend on the aetiology, but could be increased by contrast enhancement. The computer tomographic criteria are enumerated and compared with those of echo cardiography. Examples of the most important differential diagnoses are discussed.", "contents": "[Computer tomographic diagnosis of pericardial effusions (author's transl)]. Thirty patients with suspected pericardial effusions, or with cardiac enlargement of unknown cause were examined by computer tomography. In 19 cases a diagnosis of pericardial effusion or haematoma was made. All these cases were confirmed by echo cardiography or transthoracic puncture. The accuracy of computer tomography diagnosis did not depend on the aetiology, but could be increased by contrast enhancement. The computer tomographic criteria are enumerated and compared with those of echo cardiography. Examples of the most important differential diagnoses are discussed."} {"id": "PMID:157952", "title": "[The technique and results of spermatic vein phlebography in 136 men with primary sterility (author's transl)].", "content": "The results of selective phlebography of the spermatic vein in patients with primary sterility and suspected varicoceles are reported. In 60% of those examined there was left-sided, and in 8.8% right-sided, spermatic vein insufficiency or a varicocoele. The value of spermatic vein phlebography is borne out by the large number of anomalies of the venous system (67%) and by the finding of 82 left-sided varicoceles.", "contents": "[The technique and results of spermatic vein phlebography in 136 men with primary sterility (author's transl)]. The results of selective phlebography of the spermatic vein in patients with primary sterility and suspected varicoceles are reported. In 60% of those examined there was left-sided, and in 8.8% right-sided, spermatic vein insufficiency or a varicocoele. The value of spermatic vein phlebography is borne out by the large number of anomalies of the venous system (67%) and by the finding of 82 left-sided varicoceles."} {"id": "PMID:157953", "title": "Balloon occlusion technique for renal venography.", "content": "A method for retrograde renal venography resulting in an even distribution of contrast medium within the intrarenal venous system is described. This technique utilizes a balloon catheter for partial occlusion of the renal artery.", "contents": "Balloon occlusion technique for renal venography. A method for retrograde renal venography resulting in an even distribution of contrast medium within the intrarenal venous system is described. This technique utilizes a balloon catheter for partial occlusion of the renal artery."} {"id": "PMID:157954", "title": "[The angiographic diagnosis and differential diagnosis of inflammatory disease of bones and soft tissues (a report concerning 40 cases) (author's transl)].", "content": "The angiographic appearances of inflammatory disease of bones and soft tissues was analysed in 40 patients. The angiographic findings in inflammation of bone (28 patients) differed greatly, from normal findings (14.2%), moderate angiographic changes corresponding to the severity of the inflammatory process (32.1%), marked changes in the arterial, capillary and venous beds (42.9%) and significant local staining with little peripheral reaction (10.7%). Soft tissue inflammation on the other hand showed increased vascularity in all cases. A typical angiogram was found in 50% of cases and shows the following characteristics: vascularity as compared with the surroundings is usually increased and may be extensive, far more so than is found surrounding vascular bone foci; the contrast staining is usually ill-defined and the veins in the late phase are increased in calibre. Early venous filling is common and should not be regarded as a sign of malignancy. In 17.5% of patients the angiogram simulated a tumour; in four patients (10%) a false positive diagnosis of tumour was made, in two (5%) a tumour could not be excluded and in one case a benign tumour was diagnosed because of localised staining. None of the angiograms which had been interpreted incorrectly showed typical pathological vessels, which are the most important tumour criteria.", "contents": "[The angiographic diagnosis and differential diagnosis of inflammatory disease of bones and soft tissues (a report concerning 40 cases) (author's transl)]. The angiographic appearances of inflammatory disease of bones and soft tissues was analysed in 40 patients. The angiographic findings in inflammation of bone (28 patients) differed greatly, from normal findings (14.2%), moderate angiographic changes corresponding to the severity of the inflammatory process (32.1%), marked changes in the arterial, capillary and venous beds (42.9%) and significant local staining with little peripheral reaction (10.7%). Soft tissue inflammation on the other hand showed increased vascularity in all cases. A typical angiogram was found in 50% of cases and shows the following characteristics: vascularity as compared with the surroundings is usually increased and may be extensive, far more so than is found surrounding vascular bone foci; the contrast staining is usually ill-defined and the veins in the late phase are increased in calibre. Early venous filling is common and should not be regarded as a sign of malignancy. In 17.5% of patients the angiogram simulated a tumour; in four patients (10%) a false positive diagnosis of tumour was made, in two (5%) a tumour could not be excluded and in one case a benign tumour was diagnosed because of localised staining. None of the angiograms which had been interpreted incorrectly showed typical pathological vessels, which are the most important tumour criteria."} {"id": "PMID:157955", "title": "[Experiences with scintiangiography as risk-free examination method without burdening the patient (author's transl)].", "content": "Scintiangiography with 99mTc was performed on a routine basis resulting in good visualisation. Under certain circumstances this method can be considered to be the method of choice, since it does not burden the patient to any significant extent and is less likely to produce complications caused by the contrast medium.", "contents": "[Experiences with scintiangiography as risk-free examination method without burdening the patient (author's transl)]. Scintiangiography with 99mTc was performed on a routine basis resulting in good visualisation. Under certain circumstances this method can be considered to be the method of choice, since it does not burden the patient to any significant extent and is less likely to produce complications caused by the contrast medium."} {"id": "PMID:157956", "title": "[Scintigraphic and quantitative measurement of the gastric wall blood-flow of the dog (author's transl)].", "content": "In the examinations presented the gastric wall blood-flow of the dog was measured scintigraphically by using the gamma camera and quantitatively by making use of the microsphere method under different functional conditions. In doing so it became apparent that not only the individual functional stomach regions (corpus-antrum) but as well the individual stomach wall layers (mucosa-muscularis) can show a counter blood flow procedure. The two methods mentioned above have proved to be suitable both for the determination of the gastric wall blood flow in the individual layers and the optical reproduction of the regional blood-flow procedure.", "contents": "[Scintigraphic and quantitative measurement of the gastric wall blood-flow of the dog (author's transl)]. In the examinations presented the gastric wall blood-flow of the dog was measured scintigraphically by using the gamma camera and quantitatively by making use of the microsphere method under different functional conditions. In doing so it became apparent that not only the individual functional stomach regions (corpus-antrum) but as well the individual stomach wall layers (mucosa-muscularis) can show a counter blood flow procedure. The two methods mentioned above have proved to be suitable both for the determination of the gastric wall blood flow in the individual layers and the optical reproduction of the regional blood-flow procedure."} {"id": "PMID:157957", "title": "[The film-mammographic demonstration of micro-calcification (author's transl)].", "content": "The smallest dimension (dmin) of circular, isolated micro-calcifications in breast tissue was studied in relation to the degree of calcification (weight-per cent-appetite), relative scatter and the film properties of screenless mammography films. From our own investigations on phantoms, the smallest signal-to-noise ratio (delta S min/delta R) was obtained which determines the minimal contrast, given the film properties (film response S, film gradient gamma) and the amount of scatter. An approximate formula for dmin has been derived which incorporates the ROC concept.", "contents": "[The film-mammographic demonstration of micro-calcification (author's transl)]. The smallest dimension (dmin) of circular, isolated micro-calcifications in breast tissue was studied in relation to the degree of calcification (weight-per cent-appetite), relative scatter and the film properties of screenless mammography films. From our own investigations on phantoms, the smallest signal-to-noise ratio (delta S min/delta R) was obtained which determines the minimal contrast, given the film properties (film response S, film gradient gamma) and the amount of scatter. An approximate formula for dmin has been derived which incorporates the ROC concept."} {"id": "PMID:157958", "title": "[A comparison of radiation exposure of angiographers using an above-table or below-table image intensifier (author's transl)].", "content": "Phantom measurements in the vicinity of an angiographic installation with the image intensifier below the table and subsequently with the intensifier above the table have shown that the former arrangement produces three times as much radiation to the head, gonads and leg during screening than when the intensifier is above the table. This has been confirmed in clinical practice during angioplastic procedures in other units. There is also a factor of 2.6 in favour of the above table intensifier applied to the lens of the eye of the investigator Radiation to the hand of the investigator is at least half with the above table arrangement.", "contents": "[A comparison of radiation exposure of angiographers using an above-table or below-table image intensifier (author's transl)]. Phantom measurements in the vicinity of an angiographic installation with the image intensifier below the table and subsequently with the intensifier above the table have shown that the former arrangement produces three times as much radiation to the head, gonads and leg during screening than when the intensifier is above the table. This has been confirmed in clinical practice during angioplastic procedures in other units. There is also a factor of 2.6 in favour of the above table intensifier applied to the lens of the eye of the investigator Radiation to the hand of the investigator is at least half with the above table arrangement."} {"id": "PMID:157971", "title": "Evidence for a correlation between late replication and autosomal gene inactivation in a familial translocation t(X;21).", "content": "A familial translocation t(X;21)(q2700;q11) is studied. A girl, trisomic for almost all the chromosome 21, has a mildly abnormal phenotype. A second girl, phenotypically abnormal, is monosomic for the juxtacentromeric region of chromosome 21 only. A comparison of the replication pattern and of the activity of superoxide dismutase (gene located on chromosome 21) shows a clear correlation between late replication, gene inactivation and phenotype expression of chromsome 21.", "contents": "Evidence for a correlation between late replication and autosomal gene inactivation in a familial translocation t(X;21). A familial translocation t(X;21)(q2700;q11) is studied. A girl, trisomic for almost all the chromosome 21, has a mildly abnormal phenotype. A second girl, phenotypically abnormal, is monosomic for the juxtacentromeric region of chromosome 21 only. A comparison of the replication pattern and of the activity of superoxide dismutase (gene located on chromosome 21) shows a clear correlation between late replication, gene inactivation and phenotype expression of chromsome 21."} {"id": "PMID:157977", "title": "Aberrant secondary antibody responses to sheep erythrocytes in rabbits with experimental syphilis.", "content": "Rabbits infected with Treponema pallidum have strikingly depressed in vivo immunoglobulin G responses to sheep erythrocytes. To gain further insight into the nature of this suppression, the immune responses of splenic and peripheral blood lymphocytes from infected rabbits to sheep erythrocytes were studied in vitro. Spleen cells from rabbits that had been sensitized with sheep erythrocytes during active syphilis had greatly decreased immunoglobulin M and G responses after in vitro incubation with sheep erythrocytes, when compared to the results obtained with cells from sensitized uninfected animals. Suppressor cells could be demonstrated in peripheral blood lymphocytes of control rabbits 6 months after sensitization with sheep erythrocytes; these cells could be removed by nylon wool filtration. When primary sensitization with sheep erythrocytes was carried out during active syphilis, these suppressor cells were not detectable in peripheral blood lymphocytes 6 to 9 months later. These findings provide further evidence that induction of immune responses may be abnormal early in treponemal infection and may help to explain the failure of the host to produce antibodies which eradicate the organism during the first 2 to 3 months of infection.", "contents": "Aberrant secondary antibody responses to sheep erythrocytes in rabbits with experimental syphilis. Rabbits infected with Treponema pallidum have strikingly depressed in vivo immunoglobulin G responses to sheep erythrocytes. To gain further insight into the nature of this suppression, the immune responses of splenic and peripheral blood lymphocytes from infected rabbits to sheep erythrocytes were studied in vitro. Spleen cells from rabbits that had been sensitized with sheep erythrocytes during active syphilis had greatly decreased immunoglobulin M and G responses after in vitro incubation with sheep erythrocytes, when compared to the results obtained with cells from sensitized uninfected animals. Suppressor cells could be demonstrated in peripheral blood lymphocytes of control rabbits 6 months after sensitization with sheep erythrocytes; these cells could be removed by nylon wool filtration. When primary sensitization with sheep erythrocytes was carried out during active syphilis, these suppressor cells were not detectable in peripheral blood lymphocytes 6 to 9 months later. These findings provide further evidence that induction of immune responses may be abnormal early in treponemal infection and may help to explain the failure of the host to produce antibodies which eradicate the organism during the first 2 to 3 months of infection."} {"id": "PMID:157978", "title": "Ecological determinants in microbial colonization of the murine gastrointestinal tract: adherence of Torulopsis pintolopesii to epithelial surfaces.", "content": "Torulopsis pintolopesii is a yeast indigenous to the gastrointestinal tracts of conventional mice and rats from many colonies. In such natively colonized animals, the organism forms layers on the surface of the epithelium in the secreting portion of the stomach and can be cultured from all areas of the gastrointestinal tract. When given in water or food to germfree mice or specific pathogen-free mice possessing an indigenous microbiota free of yeast, T. pintolopesii also can be cultured from all areas of the tract at population levels ranging from 10(5) to 10(8) cells per g (wet weight). Likewise, as in its native hosts, the organism forms layers on gastric surfaces in the associated animals. The layers form on the secreting surface in both the specific pathogen-free and monoassociated ex-germfree mice. In the latter animal, however, a layer of yeast also forms on the nonsecreting gastric surface. In tests of its capacity to adhere to gastrointestinal surfaces in vitro, the organism adheres to epithelia from all areas of the mouse tract. These findings support an hypothesis that the capacity of T. pintolopesii to adhere to epithelial surfaces may be only one determinant influencing it to form layers on the gastric secreting surface in its native hosts.", "contents": "Ecological determinants in microbial colonization of the murine gastrointestinal tract: adherence of Torulopsis pintolopesii to epithelial surfaces. Torulopsis pintolopesii is a yeast indigenous to the gastrointestinal tracts of conventional mice and rats from many colonies. In such natively colonized animals, the organism forms layers on the surface of the epithelium in the secreting portion of the stomach and can be cultured from all areas of the gastrointestinal tract. When given in water or food to germfree mice or specific pathogen-free mice possessing an indigenous microbiota free of yeast, T. pintolopesii also can be cultured from all areas of the tract at population levels ranging from 10(5) to 10(8) cells per g (wet weight). Likewise, as in its native hosts, the organism forms layers on gastric surfaces in the associated animals. The layers form on the secreting surface in both the specific pathogen-free and monoassociated ex-germfree mice. In the latter animal, however, a layer of yeast also forms on the nonsecreting gastric surface. In tests of its capacity to adhere to gastrointestinal surfaces in vitro, the organism adheres to epithelia from all areas of the mouse tract. These findings support an hypothesis that the capacity of T. pintolopesii to adhere to epithelial surfaces may be only one determinant influencing it to form layers on the gastric secreting surface in its native hosts."} {"id": "PMID:157979", "title": "Alterations of the immune response associated with chronic experimental leishmaniasis.", "content": "BALB/c mice infected with Leishmania mexicana developed a chronic infection usually accompanied by the appearance of metastatic lesions. Throughout the 20 weeks of observation, infected mice ;howed an impairment in both in vivo delayed hypersensitivity response and in vitro lymphocyte reactivity to leishmanial antigen. Four to 8 weeks after inoculation infected mice displayed a transitory enhancement of spleen cell responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide. At the same time, immunization with sheep erythrocytes resulted in a greater number of immunoglobulin P, lipopolysaccharide, and sheep erythrocytes diminished progressively, whereas reactivity to concanavalin A was markedly augmented. When cocultivated with spleen cells from mice infected for 12 to 20 weeks, normal lymphocyte responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide were drastically reduced. These results suggest a role for suppressor cells in chronic experimental cutaneous leishmaniasis.", "contents": "Alterations of the immune response associated with chronic experimental leishmaniasis. BALB/c mice infected with Leishmania mexicana developed a chronic infection usually accompanied by the appearance of metastatic lesions. Throughout the 20 weeks of observation, infected mice ;howed an impairment in both in vivo delayed hypersensitivity response and in vitro lymphocyte reactivity to leishmanial antigen. Four to 8 weeks after inoculation infected mice displayed a transitory enhancement of spleen cell responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide. At the same time, immunization with sheep erythrocytes resulted in a greater number of immunoglobulin P, lipopolysaccharide, and sheep erythrocytes diminished progressively, whereas reactivity to concanavalin A was markedly augmented. When cocultivated with spleen cells from mice infected for 12 to 20 weeks, normal lymphocyte responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide were drastically reduced. These results suggest a role for suppressor cells in chronic experimental cutaneous leishmaniasis."} {"id": "PMID:157980", "title": "Intestinal and serum antibody responses in mice after oral immunization with Salmonella, Escherichia coli, and Salmonella-Escherichia coli hybrid strains.", "content": "After oral feeding of mice with avirulent Salmonella, Escherichia coli, or hybrid strains, only certain bacterial strains were able to multiply and persist within the small intestinal Peyer's patches. After oral vaccination alone, or oral priming and subsequent parenteral boosting, antibody class and titers were detected, using a radioimmunoassay on serum and intestinal fluid or a plaque-forming cell assay on spleens. Only those strains that persisted in the Peyer's patches stimulated the production of serum and intestinal immunoglobulin A antibodies against their respective O antigens. Nonpersistent strains were weakly immunogenic, and antibodies, when present, were largely non-immunoglobulin A and confined to the serum.", "contents": "Intestinal and serum antibody responses in mice after oral immunization with Salmonella, Escherichia coli, and Salmonella-Escherichia coli hybrid strains. After oral feeding of mice with avirulent Salmonella, Escherichia coli, or hybrid strains, only certain bacterial strains were able to multiply and persist within the small intestinal Peyer's patches. After oral vaccination alone, or oral priming and subsequent parenteral boosting, antibody class and titers were detected, using a radioimmunoassay on serum and intestinal fluid or a plaque-forming cell assay on spleens. Only those strains that persisted in the Peyer's patches stimulated the production of serum and intestinal immunoglobulin A antibodies against their respective O antigens. Nonpersistent strains were weakly immunogenic, and antibodies, when present, were largely non-immunoglobulin A and confined to the serum."} {"id": "PMID:157981", "title": "Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation.", "content": "Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer.", "contents": "Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation. Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer."} {"id": "PMID:157986", "title": "Training in rehabilitation: basics needs and considerations.", "content": "Rehabilitation is an integral part of medicine. It includes physical therapy, occupational therapy, speech therapy. It involves nurses, social workers, clinical and educational psychologists. It also involves resettlement into the community and to work. Each patient, whether temporarily or permanently disabled, requires a comprehensive service to meet all his needs at the appropriate time. Although there are some multidisciplinary teams providing comprehensive rehabilitation services the needs are so wide and complex that many patients do not achieve optimum rehabilitation. Most doctors believe that the best rehabilitation stems from high standards of general medical care, but many patients require care and counselling extending into social and community aspects of their lives. The clinician must be trained to understand these needs and accept the responsibility for, at least, initiating appropriate rehabilitation and resettlement procedures and thus reducing clinical and social morbidity. Rehabilitation is more than the practice of special techniques. Most therapists can contribute considerably by the assessment of potential functional capability and by exploiting residual capability by alternative techniques of activity, or the use of aids and appliances. The behavioural aspects of response to illness or injury and the patterns of recovery thus determined need to be more clearly understood and the rehabilitation programme reappraised in the light of the knowledge.", "contents": "Training in rehabilitation: basics needs and considerations. Rehabilitation is an integral part of medicine. It includes physical therapy, occupational therapy, speech therapy. It involves nurses, social workers, clinical and educational psychologists. It also involves resettlement into the community and to work. Each patient, whether temporarily or permanently disabled, requires a comprehensive service to meet all his needs at the appropriate time. Although there are some multidisciplinary teams providing comprehensive rehabilitation services the needs are so wide and complex that many patients do not achieve optimum rehabilitation. Most doctors believe that the best rehabilitation stems from high standards of general medical care, but many patients require care and counselling extending into social and community aspects of their lives. The clinician must be trained to understand these needs and accept the responsibility for, at least, initiating appropriate rehabilitation and resettlement procedures and thus reducing clinical and social morbidity. Rehabilitation is more than the practice of special techniques. Most therapists can contribute considerably by the assessment of potential functional capability and by exploiting residual capability by alternative techniques of activity, or the use of aids and appliances. The behavioural aspects of response to illness or injury and the patterns of recovery thus determined need to be more clearly understood and the rehabilitation programme reappraised in the light of the knowledge."} {"id": "PMID:157987", "title": "Disablement in society: towards an integrated perspective.", "content": "Demographic and morbidity changes have undermined traditional responses to disease and disability. An expanded model of disablement is required, integrating consequences as well as causes. Three main concepts involved are impairment, disability, and handicap. These constitute a continuum ranging from bio-medical phenomena (impairment) through functional limitation and activity restriction (disability) to social disadvantage (handicap). Though complete sequences can occur, analytical and practical problems arise from the fact that their interrelationship is not always straightforward or predictable. From an analysis of available data it is calculated that 34% of the adult population in Great Britain are impaired. A tenth of these are severely disabled. The age structure and underlying causes of disablement challenge prevailing stereotypes: disablement becomes more frequent with age and it is caused in large part by chronic diseases. An attempt to assess handicap direct, rather than as a derivative of disability, displays severe disadvantages among the disabled. The model allows the possibility of gathering information relevant to different aspects of disablement and warns against reductionist or naive responses in health care and social policy.", "contents": "Disablement in society: towards an integrated perspective. Demographic and morbidity changes have undermined traditional responses to disease and disability. An expanded model of disablement is required, integrating consequences as well as causes. Three main concepts involved are impairment, disability, and handicap. These constitute a continuum ranging from bio-medical phenomena (impairment) through functional limitation and activity restriction (disability) to social disadvantage (handicap). Though complete sequences can occur, analytical and practical problems arise from the fact that their interrelationship is not always straightforward or predictable. From an analysis of available data it is calculated that 34% of the adult population in Great Britain are impaired. A tenth of these are severely disabled. The age structure and underlying causes of disablement challenge prevailing stereotypes: disablement becomes more frequent with age and it is caused in large part by chronic diseases. An attempt to assess handicap direct, rather than as a derivative of disability, displays severe disadvantages among the disabled. The model allows the possibility of gathering information relevant to different aspects of disablement and warns against reductionist or naive responses in health care and social policy."} {"id": "PMID:157982", "title": "Resistances to naturalistic observation in a geriatric setting.", "content": "Two residential floors for the disabled in a Home for the Jewish Aged were the setttings for this research. One stationary camera with an audio-video taping system was used on each floor to collect data on staff-elderly interactions. This procedure permitted systematic comparisons of staff-initiated touching in relation to naturalistic variations in (1) the physical appearances of patients, and (2) the sex, age, and social statuses of interaction partners. This procedure is discussed with regard to the methodological and ethical problems it posed.", "contents": "Resistances to naturalistic observation in a geriatric setting. Two residential floors for the disabled in a Home for the Jewish Aged were the setttings for this research. One stationary camera with an audio-video taping system was used on each floor to collect data on staff-elderly interactions. This procedure permitted systematic comparisons of staff-initiated touching in relation to naturalistic variations in (1) the physical appearances of patients, and (2) the sex, age, and social statuses of interaction partners. This procedure is discussed with regard to the methodological and ethical problems it posed."} {"id": "PMID:157988", "title": "Communication and cooperation between professionals in the field of rehabilitation.", "content": "Some criteria and characteristics of Rehabilitation as a complex, multidimensional and interdisciplinary field of theory, practice and research are pointed out at the beginning of this paper. It is shown, that such a rehabilitation concept demands the cooperation between professionals in this field (a) in practice within the rehabilitation team, (b) in research for the realization of well coordinated and problem-oriented interdisciplinary projects, (c) in theory for the development of more adequate theoretical concepts and better strategies for teaching and training personnel. Improved mutual information on an international level is regarded as a basis or prerequisite for such cooperation. The multiple dimensions and directions of communication necessary to assure such cooperation are illustrated. In a description of barriers to communication in the field of rehabilitation the following facts are considered as possible causes for the present insufficient cooperation among professionals in this field- (1) specialization and exclusiveness, (2) language and presentation, (3) differences in culture, demographical situations and economic/historical development, (4) geographical, national, legal or administrative barriers, (5) professional competition, patenting and copyright, (6) lack of adequate documentation and dissemination of information, (7) inadequate use of existing information systems and communication channels. The article closes with suggestions on ways to improve communications and cooperation between professionals in rehabilitation.", "contents": "Communication and cooperation between professionals in the field of rehabilitation. Some criteria and characteristics of Rehabilitation as a complex, multidimensional and interdisciplinary field of theory, practice and research are pointed out at the beginning of this paper. It is shown, that such a rehabilitation concept demands the cooperation between professionals in this field (a) in practice within the rehabilitation team, (b) in research for the realization of well coordinated and problem-oriented interdisciplinary projects, (c) in theory for the development of more adequate theoretical concepts and better strategies for teaching and training personnel. Improved mutual information on an international level is regarded as a basis or prerequisite for such cooperation. The multiple dimensions and directions of communication necessary to assure such cooperation are illustrated. In a description of barriers to communication in the field of rehabilitation the following facts are considered as possible causes for the present insufficient cooperation among professionals in this field- (1) specialization and exclusiveness, (2) language and presentation, (3) differences in culture, demographical situations and economic/historical development, (4) geographical, national, legal or administrative barriers, (5) professional competition, patenting and copyright, (6) lack of adequate documentation and dissemination of information, (7) inadequate use of existing information systems and communication channels. The article closes with suggestions on ways to improve communications and cooperation between professionals in rehabilitation."} {"id": "PMID:157983", "title": "Local estimates of the functionally disabled elderly: toward a planning tool for housing and support service programs.", "content": "In order to allocate housing and support service funds, local planners need to know the number of elderly at various levels of functional disability. When the levels of disability are sufficiently specific, the need for specialized housing and support services can be identified, the proper funding priorities can be established, and new support programs developed. Locally administered surveys to determine functional disabilities are cost prohibitive, so estimates using secondary data are often used. This paper describes research to improve the accuracy of synthetic estimates of elderly with functional disabilities while expanding the number of functional ability levels used to describe the population.", "contents": "Local estimates of the functionally disabled elderly: toward a planning tool for housing and support service programs. In order to allocate housing and support service funds, local planners need to know the number of elderly at various levels of functional disability. When the levels of disability are sufficiently specific, the need for specialized housing and support services can be identified, the proper funding priorities can be established, and new support programs developed. Locally administered surveys to determine functional disabilities are cost prohibitive, so estimates using secondary data are often used. This paper describes research to improve the accuracy of synthetic estimates of elderly with functional disabilities while expanding the number of functional ability levels used to describe the population."} {"id": "PMID:157991", "title": "The application of Kelly's Repotory Grid Technique to investigate disabled people's perceptions of their professional workers.", "content": "Blaxter, (1976), has shown that there is an amount of confusion and misunderstanding of British medical and social services among disabled people. This study attempts to explore the perceptions of just two young disabled women to ascertain their individual views of what is seemingly a very complex array of services. No attempt has been made to generalise the findings, although future work, using group data, may be completed at a later date. The main objective of the study was to find out if Kelly's Repertory Grid Technique could be applied to this particular problem. The technique was used alongside indepth interviews. In general, the grid analysis did concur with the content analysis of the indepth interviews, particularly if the subject used her own elicited constructs. Both informal and formal agents of help were investigated, but due to lack of space, only the analyses of the three formal agents are permitted. In both case studies, the subjects' perceptions of each formal agent varied according to her attitude towards that agent and the experiences she had in dealing with him. This was verified by comparing the relationship between constructs and elements (agents) with the discriptions given during the indepth interviews. By using McQuitty's, (1960), elementary linkage analysis, two main clusters of agents were obtained. Inclusion within either cluster was largely dependant upon whether the subject considered the agent to be an authoritarian, or peer-like figure. A number of possible applications of the reportory grid technique, for future research, are also discussed.", "contents": "The application of Kelly's Repotory Grid Technique to investigate disabled people's perceptions of their professional workers. Blaxter, (1976), has shown that there is an amount of confusion and misunderstanding of British medical and social services among disabled people. This study attempts to explore the perceptions of just two young disabled women to ascertain their individual views of what is seemingly a very complex array of services. No attempt has been made to generalise the findings, although future work, using group data, may be completed at a later date. The main objective of the study was to find out if Kelly's Repertory Grid Technique could be applied to this particular problem. The technique was used alongside indepth interviews. In general, the grid analysis did concur with the content analysis of the indepth interviews, particularly if the subject used her own elicited constructs. Both informal and formal agents of help were investigated, but due to lack of space, only the analyses of the three formal agents are permitted. In both case studies, the subjects' perceptions of each formal agent varied according to her attitude towards that agent and the experiences she had in dealing with him. This was verified by comparing the relationship between constructs and elements (agents) with the discriptions given during the indepth interviews. By using McQuitty's, (1960), elementary linkage analysis, two main clusters of agents were obtained. Inclusion within either cluster was largely dependant upon whether the subject considered the agent to be an authoritarian, or peer-like figure. A number of possible applications of the reportory grid technique, for future research, are also discussed."} {"id": "PMID:158003", "title": "[The facial mask as a basis of clindamycin therapy for acne vulgaris].", "content": "In 29 healthy male subjects aged between 20 to 25 years a powder face mask, consisting of 1.19% clindamycin phosphate (= 1% clindamycin base) in 70% ethanol was applied to the right side of the forehead once daily over a period of 5 days. At the same time half of the test subjects were treated in the same way on the left side of the forehead with a solution consisting of 1.19% clindamycin phosphate in 70% ethanol, and the other half with the same powder mask as on the right side but without clindamycin phosphate. The face mask containing clindamycin phosphate leads to a greater reduction of P. acnes. the total propionibacteria and the total bacterial counts (anaerobic culture) in the pilosebaceous duct than both other preparations. Compared with the initial values these do, however, reduce the bacterial count. The use of face masks containing antibiotics seems to offer a successful way of topical antibiotic treatment of acne.", "contents": "[The facial mask as a basis of clindamycin therapy for acne vulgaris]. In 29 healthy male subjects aged between 20 to 25 years a powder face mask, consisting of 1.19% clindamycin phosphate (= 1% clindamycin base) in 70% ethanol was applied to the right side of the forehead once daily over a period of 5 days. At the same time half of the test subjects were treated in the same way on the left side of the forehead with a solution consisting of 1.19% clindamycin phosphate in 70% ethanol, and the other half with the same powder mask as on the right side but without clindamycin phosphate. The face mask containing clindamycin phosphate leads to a greater reduction of P. acnes. the total propionibacteria and the total bacterial counts (anaerobic culture) in the pilosebaceous duct than both other preparations. Compared with the initial values these do, however, reduce the bacterial count. The use of face masks containing antibiotics seems to offer a successful way of topical antibiotic treatment of acne."} {"id": "PMID:158004", "title": "A histochemical study about changes in rat liver plasma membrane enzyme activities after galactosamine administration.", "content": "In rats changes in plasma membrane enzyme activities due to Gal-N intoxication were studied by enzymehistochemical methods. The bile canalicular 5'-nucleotidase and nucleoside polyphosphatase activities decreased; the sinusoidal 5'-nucleotidase remained unchanged. The bile canalicular leucyl-beta-naphthyl-amidase showed an increase in activity; the alkaline phosphatase activity remained unchanged. In contrast to the spotty necrosis, changes in plasma membrane enzyme activities were seen in all liver cells, suggesting that changes of these activities, occurring after Gal-N treatment, do not correlate with cell death. The conclusion was drawn that the deviations of the enzyme activities might be due to changes in the lipid environment of the enzyme proteins in the membrane. With the exception of alkaline phosphatase, partial hepatectomy caused the same changes in enzyme activities as did Gal-N intoxication. Nevertheless Gal-N administration to partial hepatectomized rats did not lead to hepatic necrosis. Galactose given simultaneously or within two hours after Gal-N prevented both changes in plasma membrane enzyme activities and hepatocellular damage. This suggests an important role of galactolipids and galactoproteins in the plasma membrane alterations.", "contents": "A histochemical study about changes in rat liver plasma membrane enzyme activities after galactosamine administration. In rats changes in plasma membrane enzyme activities due to Gal-N intoxication were studied by enzymehistochemical methods. The bile canalicular 5'-nucleotidase and nucleoside polyphosphatase activities decreased; the sinusoidal 5'-nucleotidase remained unchanged. The bile canalicular leucyl-beta-naphthyl-amidase showed an increase in activity; the alkaline phosphatase activity remained unchanged. In contrast to the spotty necrosis, changes in plasma membrane enzyme activities were seen in all liver cells, suggesting that changes of these activities, occurring after Gal-N treatment, do not correlate with cell death. The conclusion was drawn that the deviations of the enzyme activities might be due to changes in the lipid environment of the enzyme proteins in the membrane. With the exception of alkaline phosphatase, partial hepatectomy caused the same changes in enzyme activities as did Gal-N intoxication. Nevertheless Gal-N administration to partial hepatectomized rats did not lead to hepatic necrosis. Galactose given simultaneously or within two hours after Gal-N prevented both changes in plasma membrane enzyme activities and hepatocellular damage. This suggests an important role of galactolipids and galactoproteins in the plasma membrane alterations."} {"id": "PMID:158006", "title": "Gene lon and plasmid inheritance in Escherichia coli K-12.", "content": "Lon- mutants of Escherichia coli K-12 are deficient in the inheritance of F-plasmids by conjugation. This deficiency is distinct from the conjugation deficiency caused by overproduction of capsular polysaccharide which decreases donor-recipient pair formation.", "contents": "Gene lon and plasmid inheritance in Escherichia coli K-12. Lon- mutants of Escherichia coli K-12 are deficient in the inheritance of F-plasmids by conjugation. This deficiency is distinct from the conjugation deficiency caused by overproduction of capsular polysaccharide which decreases donor-recipient pair formation."} {"id": "PMID:158007", "title": "Lambda bacteriophage-mediated transduction of ColE1 deoxyribonucleic acid having a lambda bacteriophage-cohesive end site: selection of packageable-length deoxyribonucleic acid.", "content": "An in vitro recombinant ColE1-cos lambda deoxyribonucleic acid (DNA) molecule, pKY96, has 70% of the length of lambda phage DNA. The process of lambda phage-mediated transduction of pKY96 generated a small amount of transducing phage particles containing ColE1-cos lambda DNA molecules of 80 or 101% of the length of lambda phage DNA, in addition to those containing original pKY96 DNA molecules. The newly isolated larger plasmid DNAs were transduced 100 times more efficiently than pKY96 DNA. Their structures were compared with that of a prototype pKY96 DNA, and the mechanism of the formation of these molecules is discussed.", "contents": "Lambda bacteriophage-mediated transduction of ColE1 deoxyribonucleic acid having a lambda bacteriophage-cohesive end site: selection of packageable-length deoxyribonucleic acid. An in vitro recombinant ColE1-cos lambda deoxyribonucleic acid (DNA) molecule, pKY96, has 70% of the length of lambda phage DNA. The process of lambda phage-mediated transduction of pKY96 generated a small amount of transducing phage particles containing ColE1-cos lambda DNA molecules of 80 or 101% of the length of lambda phage DNA, in addition to those containing original pKY96 DNA molecules. The newly isolated larger plasmid DNAs were transduced 100 times more efficiently than pKY96 DNA. Their structures were compared with that of a prototype pKY96 DNA, and the mechanism of the formation of these molecules is discussed."} {"id": "PMID:158008", "title": "Circadian rhythms in Neurospora crassa: effects of saturated fatty acids.", "content": "To assess their effects on the conidiation rhythm in Neurospora, 14 saturated fatty acids from 6 to 24 carbons long were used to supplement the bd csp and bd csp cel strains. Both strains express a circadian spore-forming rhythm when grown on solid media; the cel mutation confers a partial fatty acid requirement. Fatty acid supplements from 8 to 13 carbons long lengthened the free-running period of bd csp cel compared with the control value of 21 h; the maximal effect (33 h) was obtained with nonanoic acid (9:0) at a concentration of 5 x 10(-4) M. In contrast, the period of bd csp remained unchanged under all experimental conditions. The short-chain fatty acids (<14 carbons) reduced the rate of advance of the growth front in both strains, compared with unsupplemented controls. However, this inhibition did not appear to be responsible for the lengthened periods in bd csp cel. Nor was direct incorporation of the short-chain (period-lengthening) fatty acids into mycelial total lipids responsible, since such incorporation was not observed. In fact, extensive metabolic conversion of these supplements by both strains was indicated by the disappearance of short-chain fatty acids from the agar media coupled with their absence in mycelial lipids, and by the liberation of (14)CO(2) from cultures supplemented with [1-(14)C]lauric acid (12:0).", "contents": "Circadian rhythms in Neurospora crassa: effects of saturated fatty acids. To assess their effects on the conidiation rhythm in Neurospora, 14 saturated fatty acids from 6 to 24 carbons long were used to supplement the bd csp and bd csp cel strains. Both strains express a circadian spore-forming rhythm when grown on solid media; the cel mutation confers a partial fatty acid requirement. Fatty acid supplements from 8 to 13 carbons long lengthened the free-running period of bd csp cel compared with the control value of 21 h; the maximal effect (33 h) was obtained with nonanoic acid (9:0) at a concentration of 5 x 10(-4) M. In contrast, the period of bd csp remained unchanged under all experimental conditions. The short-chain fatty acids (<14 carbons) reduced the rate of advance of the growth front in both strains, compared with unsupplemented controls. However, this inhibition did not appear to be responsible for the lengthened periods in bd csp cel. Nor was direct incorporation of the short-chain (period-lengthening) fatty acids into mycelial total lipids responsible, since such incorporation was not observed. In fact, extensive metabolic conversion of these supplements by both strains was indicated by the disappearance of short-chain fatty acids from the agar media coupled with their absence in mycelial lipids, and by the liberation of (14)CO(2) from cultures supplemented with [1-(14)C]lauric acid (12:0)."} {"id": "PMID:158009", "title": "On the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum induced by thymol.", "content": "The mechanism was studied of the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum (FSR) which is observed when the active transport of calcium into FSR is performed in the presence of thymol; the amount of calcium in FSR increases steeply during the first minute of the reaction and then decreases markedly. In contrast to this behavior, the amount of calcium in FSR increases monotonically and then reaches saturation in the absence of thymol. It is shown that the amount of calcium accumulated in FSR is determined by the balance between the rapid influx and efflux of calcium, and that both processes are depressed by thymol. The overshoot of calcium accumulation can be explained as follows: thymol so markedly depresses the efflux of calcium uncoupled with Ca2+-ATPase activity that the amount of calcium is increased in FSR in spite of partial deactivation of Ca2+-ATPase. However, the state of the FSR membrane is rapidly changed when the concentration of accumulated calcium exceeds a certain critical value. Concomitant with this change, the calcium permeability of the membrane is increased, leading to a decrease in the amount of accumulated calcium. The effects of magnesium and temperature on the overshoot of calcium accumulation can be accounted for by this proposed mechanism.", "contents": "On the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum induced by thymol. The mechanism was studied of the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum (FSR) which is observed when the active transport of calcium into FSR is performed in the presence of thymol; the amount of calcium in FSR increases steeply during the first minute of the reaction and then decreases markedly. In contrast to this behavior, the amount of calcium in FSR increases monotonically and then reaches saturation in the absence of thymol. It is shown that the amount of calcium accumulated in FSR is determined by the balance between the rapid influx and efflux of calcium, and that both processes are depressed by thymol. The overshoot of calcium accumulation can be explained as follows: thymol so markedly depresses the efflux of calcium uncoupled with Ca2+-ATPase activity that the amount of calcium is increased in FSR in spite of partial deactivation of Ca2+-ATPase. However, the state of the FSR membrane is rapidly changed when the concentration of accumulated calcium exceeds a certain critical value. Concomitant with this change, the calcium permeability of the membrane is increased, leading to a decrease in the amount of accumulated calcium. The effects of magnesium and temperature on the overshoot of calcium accumulation can be accounted for by this proposed mechanism."} {"id": "PMID:158010", "title": "Studies on stringent control in a cell-free system. Regulation by guanosine-5'-diphosphate-3'-diphosphate of the synthesis of elongation factor Tu.", "content": "The biosynthesis of elongation factor Tu (EF-Tu) has been studied in a cell-free system with DNA of the transducing phage lambdarifd18 as a template. It was found that the synthesis of EF-Tu in this system was inhibited by about 60% in the presence of 0.3 to 0.6 mM guanosine-5'-diphosphate-3'-diphosphate (ppGpp). The syntheses of several ribosomal proteins encoded in this template, i.e. L1, L10, L11, and L7/L12, were also depressed, whereas those of phage lambda proteins were rather enhanced by the addition of ppGpp. By separating the reaction into two steps, i.e., transcription and translation, the effect of ppGpp was shown to occur at the level of transcription. Several analogs, such as guanosine-5'-diphosphate-3'-monophosphate (ppGp) and guanosine-5'-diphosphate (ppG), were without effect. The formation of mRNA for EF-Tu was assessed directly by specific hybridization with pTUA1 DNA carrying tufA gene. The results clearly indicated that the synthesis of tufB . MRNA was severely and selectively inhibited by ppGpp.", "contents": "Studies on stringent control in a cell-free system. Regulation by guanosine-5'-diphosphate-3'-diphosphate of the synthesis of elongation factor Tu. The biosynthesis of elongation factor Tu (EF-Tu) has been studied in a cell-free system with DNA of the transducing phage lambdarifd18 as a template. It was found that the synthesis of EF-Tu in this system was inhibited by about 60% in the presence of 0.3 to 0.6 mM guanosine-5'-diphosphate-3'-diphosphate (ppGpp). The syntheses of several ribosomal proteins encoded in this template, i.e. L1, L10, L11, and L7/L12, were also depressed, whereas those of phage lambda proteins were rather enhanced by the addition of ppGpp. By separating the reaction into two steps, i.e., transcription and translation, the effect of ppGpp was shown to occur at the level of transcription. Several analogs, such as guanosine-5'-diphosphate-3'-monophosphate (ppGp) and guanosine-5'-diphosphate (ppG), were without effect. The formation of mRNA for EF-Tu was assessed directly by specific hybridization with pTUA1 DNA carrying tufA gene. The results clearly indicated that the synthesis of tufB . MRNA was severely and selectively inhibited by ppGpp."} {"id": "PMID:158011", "title": "Kinetic properties of dynein ATPase from Tetrahymena pyriformis. The initial phosphate burst of dynein ATPase and its interaction with ATP analogs.", "content": "1. Dynein was extracted with 0.5 M KCl from Tetrahymena axonemes. SDS-gel electrophoresis of the extract indicated that about 50% of the extracted protein had a molecular weight of about 3.5 X 10(5), and that 90% of the proteins with this weight had been extracted. 2. The ATPase [EC 3.6.1.3] reaction of the KCl-extracted dynein fraction was enhanced by 60-80% by addition of the outer doublet fraction. It showed an initial burst of Pi liberation of about 1 mol per mol of proteins with a molecular weight of 3.5 X 10(5). 3. We examined the interaction of the dynein-tubulin system from Tetrahymena cilia with ten ATP analogs [2'-dATP, 3'-dATP, epsilonATP, FTP, 8-NH(CH3)-ATP, 8,3'-S-cyclo-ATP, 8-Br-ATP, 8-OCH3-ATP, 8-SCH3-ATP, and AMPPNP]. Among them, 2'-dATP and 3'-dATP were good substrates for dynein ATPase, as they induced the dissociation of dynein arms from the B-tubule of outer doublets, the sliding movement between outer doublets, and the bending movement of axonemes. The other analogs did not induce the dissociation or the sliding movement. 4. Among the ATP analogs tested, only 2'-dATP and 3'-dATP induced the reorientation of cilia on the Triton model of Tetrahymena; the reorientation rates were smaller than that induced by ATP.", "contents": "Kinetic properties of dynein ATPase from Tetrahymena pyriformis. The initial phosphate burst of dynein ATPase and its interaction with ATP analogs. 1. Dynein was extracted with 0.5 M KCl from Tetrahymena axonemes. SDS-gel electrophoresis of the extract indicated that about 50% of the extracted protein had a molecular weight of about 3.5 X 10(5), and that 90% of the proteins with this weight had been extracted. 2. The ATPase [EC 3.6.1.3] reaction of the KCl-extracted dynein fraction was enhanced by 60-80% by addition of the outer doublet fraction. It showed an initial burst of Pi liberation of about 1 mol per mol of proteins with a molecular weight of 3.5 X 10(5). 3. We examined the interaction of the dynein-tubulin system from Tetrahymena cilia with ten ATP analogs [2'-dATP, 3'-dATP, epsilonATP, FTP, 8-NH(CH3)-ATP, 8,3'-S-cyclo-ATP, 8-Br-ATP, 8-OCH3-ATP, 8-SCH3-ATP, and AMPPNP]. Among them, 2'-dATP and 3'-dATP were good substrates for dynein ATPase, as they induced the dissociation of dynein arms from the B-tubule of outer doublets, the sliding movement between outer doublets, and the bending movement of axonemes. The other analogs did not induce the dissociation or the sliding movement. 4. Among the ATP analogs tested, only 2'-dATP and 3'-dATP induced the reorientation of cilia on the Triton model of Tetrahymena; the reorientation rates were smaller than that induced by ATP."} {"id": "PMID:158013", "title": "Change in the ultraviolet spectrum of solubilized Ca2+-dependent ATPase from sarcoplasmic reticulum due to binding with Ca2+ ions.", "content": "Solubilized sarcoplasmic reticulum (SSR) was prepared by solubilizing fragmented sarcoplasmic reticulum (FSR) with a nonionic detergent (C12E8) then displacing the detergent with Tween 80, using a DEAE-cellulose column. The UV absorption of SSR decreased reversibly at about 286 and 292 nm on removal of free Ca2+ ions, while no change in the fluorescence spectrum was detectable. On the other hand, the fluorescence intensity of FSR decreased 3-4% on removal of free Ca2+ ions, as previously reported by Dupont [(1976) Biochem. Biophys. Res. Commun. 71, 544-550]. The UV absorption of FSR increased reversibly at about 270-280 nm on removal of free Ca2+ ions, but the rate of the change was very slow (k = about 0.1 min-1).", "contents": "Change in the ultraviolet spectrum of solubilized Ca2+-dependent ATPase from sarcoplasmic reticulum due to binding with Ca2+ ions. Solubilized sarcoplasmic reticulum (SSR) was prepared by solubilizing fragmented sarcoplasmic reticulum (FSR) with a nonionic detergent (C12E8) then displacing the detergent with Tween 80, using a DEAE-cellulose column. The UV absorption of SSR decreased reversibly at about 286 and 292 nm on removal of free Ca2+ ions, while no change in the fluorescence spectrum was detectable. On the other hand, the fluorescence intensity of FSR decreased 3-4% on removal of free Ca2+ ions, as previously reported by Dupont [(1976) Biochem. Biophys. Res. Commun. 71, 544-550]. The UV absorption of FSR increased reversibly at about 270-280 nm on removal of free Ca2+ ions, but the rate of the change was very slow (k = about 0.1 min-1)."} {"id": "PMID:158014", "title": "Inducible and constitutive kynureninases. Control of the inducible enzyme activity by transamination and inhibition of the constitutive enzyme by 3-hydroxyanthranilate.", "content": "The inducible kynureninase from Neurospora crassa is inactivated by incubation with L-alanine or L-ornithine. The inactivated enzyme is resolved to the apoenzyme by dialysis. Reactivation of the apoenzyme is achieved by incubation with pyridoxamine 5'-phosphate plus pyruvate, as well as with pyridoxal 5'-phosphate. The kynurenine hydrolysis proceeds linearly in the presence of added pyridoxal 5'-phosphate, or pyridoxamine 5'-phosphate plus pyruvate. These findings indicate that the fungal inducible kynureninase can act as an amino-transferase to control the enzyme activity, and that the control mechanism is similar to that reported for the bacterial kynureninase (Moriguchi, M. & Soda, K. (1973) Biochemistry 12, 2974-2980). The ratio of kynureninase activity to aminotransferase activity was determined with bacterial and fungal enzymes. All the inducible kynureninases from various fungal species examined are also controlled by the transamination. In contrast, the pig liver kynureninase and the fungal constitutive enzymes are little or not at all affected by preincubation with amino acids. Thus, the present regulatory mechanism does not operate in these constitutive-type enzymes. The rate of hydrolysis of L-3-hydroxykynurenine by the pig liver enzyme decreases with increase in the incubation time; the enzyme is inhibited by 3-hydroxyanthranilate produced from L-3-hydroxykynurenine. The inhibition is found in all the constitutive-type enzymes, suggesting that 3-hydroxyanthranilate plays a regulatory role in NAD biosynthesis from tryptophan.", "contents": "Inducible and constitutive kynureninases. Control of the inducible enzyme activity by transamination and inhibition of the constitutive enzyme by 3-hydroxyanthranilate. The inducible kynureninase from Neurospora crassa is inactivated by incubation with L-alanine or L-ornithine. The inactivated enzyme is resolved to the apoenzyme by dialysis. Reactivation of the apoenzyme is achieved by incubation with pyridoxamine 5'-phosphate plus pyruvate, as well as with pyridoxal 5'-phosphate. The kynurenine hydrolysis proceeds linearly in the presence of added pyridoxal 5'-phosphate, or pyridoxamine 5'-phosphate plus pyruvate. These findings indicate that the fungal inducible kynureninase can act as an amino-transferase to control the enzyme activity, and that the control mechanism is similar to that reported for the bacterial kynureninase (Moriguchi, M. & Soda, K. (1973) Biochemistry 12, 2974-2980). The ratio of kynureninase activity to aminotransferase activity was determined with bacterial and fungal enzymes. All the inducible kynureninases from various fungal species examined are also controlled by the transamination. In contrast, the pig liver kynureninase and the fungal constitutive enzymes are little or not at all affected by preincubation with amino acids. Thus, the present regulatory mechanism does not operate in these constitutive-type enzymes. The rate of hydrolysis of L-3-hydroxykynurenine by the pig liver enzyme decreases with increase in the incubation time; the enzyme is inhibited by 3-hydroxyanthranilate produced from L-3-hydroxykynurenine. The inhibition is found in all the constitutive-type enzymes, suggesting that 3-hydroxyanthranilate plays a regulatory role in NAD biosynthesis from tryptophan."} {"id": "PMID:158016", "title": "The presence of an adenosine-5'-triphosphatase dependent on 6S tubulin and calcium ions in rat brain microtubules.", "content": "An ATPase activity was found in rat brain microtubules prepared by successive cycles of polymerization and depolymerization. On phosphocellulose column chromatography, the ATPase activity was recovered in the fraction eluted with 0.6 M KCl and containing the microtubule associated proteins. The ATPase activity was markedly stimulated by the addition of purified brain 6S tubulin, and the stimulation was dependent on the presence of Ca2+ ions. Approximately 50 pmol of purified 6S tubulin was required for the maximal stimulation in the presence of 8 microgram of microtubule associated proteins. The specific activity was 8 to 13 nmol of ATP hydrolyzed per min per mg of protein at 37 degrees C, and the Km value for ATP was 3 X 10(-5) M in the presence of added tubulin.", "contents": "The presence of an adenosine-5'-triphosphatase dependent on 6S tubulin and calcium ions in rat brain microtubules. An ATPase activity was found in rat brain microtubules prepared by successive cycles of polymerization and depolymerization. On phosphocellulose column chromatography, the ATPase activity was recovered in the fraction eluted with 0.6 M KCl and containing the microtubule associated proteins. The ATPase activity was markedly stimulated by the addition of purified brain 6S tubulin, and the stimulation was dependent on the presence of Ca2+ ions. Approximately 50 pmol of purified 6S tubulin was required for the maximal stimulation in the presence of 8 microgram of microtubule associated proteins. The specific activity was 8 to 13 nmol of ATP hydrolyzed per min per mg of protein at 37 degrees C, and the Km value for ATP was 3 X 10(-5) M in the presence of added tubulin."} {"id": "PMID:158017", "title": "Macrophage myosin. Regulation of actin-activated ATPase, activity by phosphorylation of the 20,000-dalton light chain.", "content": "Myosin was purified from rabbit alveolar macrophages in a form that could not be activated by actin. This myosin could be phosphorylated by an endogenous myosin light chain kinase, up to 2 mol of phosphate being incorporated/mol of myosin. The site phosphorylated was located on the 20,000-dalton myosin light chain. Phosphorylation of macrophage myosin was found to be necessary for actin activation of myosin ATPase activity. Moreover, the actin-activated ATPase activity was found to vary directly with the extent of myosin phosphorylation, maximal phosphorylation (2 mol of Pi/mol of myosin) resulting in an actin-activated MgATPase activity of approximately 200 nmol of Pi/mg of myosin/min at 37 degrees C. These results establish that phosphyoyration of the 20,000-dalton light chain of myosin is sufficient to regulate the actin-activated ATPase activity of macrophage myosin.", "contents": "Macrophage myosin. Regulation of actin-activated ATPase, activity by phosphorylation of the 20,000-dalton light chain. Myosin was purified from rabbit alveolar macrophages in a form that could not be activated by actin. This myosin could be phosphorylated by an endogenous myosin light chain kinase, up to 2 mol of phosphate being incorporated/mol of myosin. The site phosphorylated was located on the 20,000-dalton myosin light chain. Phosphorylation of macrophage myosin was found to be necessary for actin activation of myosin ATPase activity. Moreover, the actin-activated ATPase activity was found to vary directly with the extent of myosin phosphorylation, maximal phosphorylation (2 mol of Pi/mol of myosin) resulting in an actin-activated MgATPase activity of approximately 200 nmol of Pi/mg of myosin/min at 37 degrees C. These results establish that phosphyoyration of the 20,000-dalton light chain of myosin is sufficient to regulate the actin-activated ATPase activity of macrophage myosin."} {"id": "PMID:158021", "title": "Rat thyroid phosphofructokinase. Comparison of the regulatory and molecular properties with those of rat muscle enzyme.", "content": "The kinetic and molecular properties of rat thyroid phosphofructokinase (specific activity 134 units/mg) were compared with those of rat muscle phosphofructokinase (specific activity 135 units/mg). Thyroid and muscle phosphofructokinase showed similar sedimentation patterns in sucrose density gradients; their affinity for DEAE-cellulose was similar but not identical. A comparison of the kinetic properties revealed differences in the pH optima. Striking differences in the kinetic properties were shown below pH 7.4; the thyroid enzyme was less inhibited by ATP or citrate and more sensitive to activation by cyclic 3':5'-AMP than the muscle enzyme. A study of the effects of some cyclic as well as linear mononucleotides, such as cyclic AMP, cyclic IMP, cyclic GMP, cyclic CMP, cyclic UMP, 5'-AMP, and 3'-AMP on thyroid phosphofructokinase showed that at concentrations as low as 1 micrometer only cyclic AMP and cyclic IMP were able to activate thyroid enzyme in the presence of low fructose-6-P and high ATP concentrations.", "contents": "Rat thyroid phosphofructokinase. Comparison of the regulatory and molecular properties with those of rat muscle enzyme. The kinetic and molecular properties of rat thyroid phosphofructokinase (specific activity 134 units/mg) were compared with those of rat muscle phosphofructokinase (specific activity 135 units/mg). Thyroid and muscle phosphofructokinase showed similar sedimentation patterns in sucrose density gradients; their affinity for DEAE-cellulose was similar but not identical. A comparison of the kinetic properties revealed differences in the pH optima. Striking differences in the kinetic properties were shown below pH 7.4; the thyroid enzyme was less inhibited by ATP or citrate and more sensitive to activation by cyclic 3':5'-AMP than the muscle enzyme. A study of the effects of some cyclic as well as linear mononucleotides, such as cyclic AMP, cyclic IMP, cyclic GMP, cyclic CMP, cyclic UMP, 5'-AMP, and 3'-AMP on thyroid phosphofructokinase showed that at concentrations as low as 1 micrometer only cyclic AMP and cyclic IMP were able to activate thyroid enzyme in the presence of low fructose-6-P and high ATP concentrations."} {"id": "PMID:158024", "title": "Orthopaedic features in the presentation of syringomyelia.", "content": "The orthopaedic surgeon is often the first consultant to whom a patient with syringomyelia is referred. The disease is not as rare as he may suppose, but its early presenting features are very variable; if he relies solely on such familiar features as pes cavus and scoliosis, he may well miss the diagnosis. The commonest presenting symptom is pain in the head, neck, trunk or limbs; headache or neckache made worse by straining is particularly significant. A history of birth injury also may suggest the possibility of syringomyelia, especially if any spasticity subsequently worsens. Neurological features which may be diagnostic include nystagmus, dissociated sensory loss, muscle wasting, spasticity of the lower limbs or Charcot's joints. Radiographic features include erosion of the bodies of cervical vertebrae and widening of the spinal canal; if, at C5, the size of the canal exceeds that of the body by 6 millimetres in the adult, pathological dilatation is present. The presence of basilar invagination or other abnormalities of the foramen magnum, of spina bifida occulta and of scoliosis are further pointers. Thermography is a useful way of showing asymmetrical sympathetic involvement in early cases. A greater awareness of the prevalence of syringomyelia may lead to earlier diagnosis and to early operation, which appears to hold out the best hope of arresting what is all too commonly a severely disabling and progressive condition.", "contents": "Orthopaedic features in the presentation of syringomyelia. The orthopaedic surgeon is often the first consultant to whom a patient with syringomyelia is referred. The disease is not as rare as he may suppose, but its early presenting features are very variable; if he relies solely on such familiar features as pes cavus and scoliosis, he may well miss the diagnosis. The commonest presenting symptom is pain in the head, neck, trunk or limbs; headache or neckache made worse by straining is particularly significant. A history of birth injury also may suggest the possibility of syringomyelia, especially if any spasticity subsequently worsens. Neurological features which may be diagnostic include nystagmus, dissociated sensory loss, muscle wasting, spasticity of the lower limbs or Charcot's joints. Radiographic features include erosion of the bodies of cervical vertebrae and widening of the spinal canal; if, at C5, the size of the canal exceeds that of the body by 6 millimetres in the adult, pathological dilatation is present. The presence of basilar invagination or other abnormalities of the foramen magnum, of spina bifida occulta and of scoliosis are further pointers. Thermography is a useful way of showing asymmetrical sympathetic involvement in early cases. A greater awareness of the prevalence of syringomyelia may lead to earlier diagnosis and to early operation, which appears to hold out the best hope of arresting what is all too commonly a severely disabling and progressive condition."} {"id": "PMID:158025", "title": "The natural history of congenital disease of the hip.", "content": "Fifty-four adults with eighty hips affected by congenital disease which had not been treated have been reviewed. Fifty-nine per cent of forty-two dislocated hips had fair or poor grading scores. The incidence of osteoarthritis was markedly increased in the presence of a well-developed false acetabulum. Unilateral dislocation led to valgus deformity and degenerative changes in the ipsilateral knee in seven of twenty-two patients. Dislocation did not increase the incidence of symptomatic lumbar spondylosis. The height of the dislocated head on the ilium was not found to be related to the prognosis for the hip, the knee or the lumbar spine and did not correlate with the development of the false acetabulum. Frank congenital subluxation eventually led to osteoarthritis of the hip.", "contents": "The natural history of congenital disease of the hip. Fifty-four adults with eighty hips affected by congenital disease which had not been treated have been reviewed. Fifty-nine per cent of forty-two dislocated hips had fair or poor grading scores. The incidence of osteoarthritis was markedly increased in the presence of a well-developed false acetabulum. Unilateral dislocation led to valgus deformity and degenerative changes in the ipsilateral knee in seven of twenty-two patients. Dislocation did not increase the incidence of symptomatic lumbar spondylosis. The height of the dislocated head on the ilium was not found to be related to the prognosis for the hip, the knee or the lumbar spine and did not correlate with the development of the false acetabulum. Frank congenital subluxation eventually led to osteoarthritis of the hip."} {"id": "PMID:158027", "title": "Mitochondrial ribosome assembly in Neurospora. Two-dimensional gel electrophoretic analysis of mitochondrial ribosomal proteins.", "content": "Recent results with Neurospora crassa show that one protein (S-5, mol wt 52,000) associated with the mitochondrial (mit) small ribosomal subunit is translated within the mitochondria (Lambowitz et al. 1976. J. Mol. Biol. 107:223-253). In the present work, Neurospora mit ribosomal proteins were analyzed by two-dimensional gel electrophoresis using a modification of the gel system of Mets and Bogorad. The results show that S-5 is present in near stoichiometric concentrations in high salt (0.5 MKCl)-washed mit small subunits from wild-type strains. S-5 is among the most basic mit ribosomal proteins (pI greater than 10) and has a high affinity for RNA under the conditions of the urea-containing gel buffers. The role of S-5 in mit ribosome assembly was investigated by an indirect method, making use of chloramphenicol to specifically inhibit mit protein synthesis. Chloramphenicol was found to rapidly inhibit the assembly of mit small subunits leading to the formation of CAP-30S particles which sediment slightly behind mature small subunits (LaPolla and Lambowitz. 1977. J. Mol. 116: 189-205). Two-dimensional gel analysis shows that the more slowly sedimentaing CAP-30S particles are deficient in S-5 and in several other proteins, whereas these proteins are present in normal concentrations in mature small subunits from the same cells. Because S-5 is the only mit ribosomal protein whose synthesis is directly inhibited by chloramphenicol, the results tentatively suggest that S-5 plays a role in the assembly of mit small subunits. In addition, the results are consistent with the idea that S-5 stabilizes the binding of several other mit small subunit proteins. Two-dimensional gel electrophoresis was used to examine mit ribosomal proteins from [poky] and six additional extra-nuclear mutants with defects in the assembly of mit small subunits. The electrophoretic mobility of S-5 is not detectably altered in any of the mutants. However, [poky] mit small subunits are deficient in S-5 and also contain several other proteins in abnormally low or high concentrations. These and other results are consistent with a defect in a mit ribosomal constituent in [poky].", "contents": "Mitochondrial ribosome assembly in Neurospora. Two-dimensional gel electrophoretic analysis of mitochondrial ribosomal proteins. Recent results with Neurospora crassa show that one protein (S-5, mol wt 52,000) associated with the mitochondrial (mit) small ribosomal subunit is translated within the mitochondria (Lambowitz et al. 1976. J. Mol. Biol. 107:223-253). In the present work, Neurospora mit ribosomal proteins were analyzed by two-dimensional gel electrophoresis using a modification of the gel system of Mets and Bogorad. The results show that S-5 is present in near stoichiometric concentrations in high salt (0.5 MKCl)-washed mit small subunits from wild-type strains. S-5 is among the most basic mit ribosomal proteins (pI greater than 10) and has a high affinity for RNA under the conditions of the urea-containing gel buffers. The role of S-5 in mit ribosome assembly was investigated by an indirect method, making use of chloramphenicol to specifically inhibit mit protein synthesis. Chloramphenicol was found to rapidly inhibit the assembly of mit small subunits leading to the formation of CAP-30S particles which sediment slightly behind mature small subunits (LaPolla and Lambowitz. 1977. J. Mol. 116: 189-205). Two-dimensional gel analysis shows that the more slowly sedimentaing CAP-30S particles are deficient in S-5 and in several other proteins, whereas these proteins are present in normal concentrations in mature small subunits from the same cells. Because S-5 is the only mit ribosomal protein whose synthesis is directly inhibited by chloramphenicol, the results tentatively suggest that S-5 plays a role in the assembly of mit small subunits. In addition, the results are consistent with the idea that S-5 stabilizes the binding of several other mit small subunit proteins. Two-dimensional gel electrophoresis was used to examine mit ribosomal proteins from [poky] and six additional extra-nuclear mutants with defects in the assembly of mit small subunits. The electrophoretic mobility of S-5 is not detectably altered in any of the mutants. However, [poky] mit small subunits are deficient in S-5 and also contain several other proteins in abnormally low or high concentrations. These and other results are consistent with a defect in a mit ribosomal constituent in [poky]."} {"id": "PMID:158028", "title": "Study of the mechanism of vanadate inhibition of the dynein cross-bridge cycle in sea urchin sperm flagella.", "content": "The effect of vanadate on the ATP-induced disruption of trypsin-treated axonemes and the ATP-induced straightening of rigor wave preparations of sea urchin sperm was investigated. Addition of ATP to a suspension of trypsin-treated axonemes results in a rapid decrease in turbidity (optical density measured at 350 nm) concomitant with the disruption of the axonemes by sliding between microtubules to form tangles of connected doublet microtubules (Summers and Gibbons, 1971; Sale and Satir, 1977). For axonemes digested to approximately 93 percent of their initial turbidity, 5 {muM} vanadate completely inhibits the ATP-induced decrease in turbidity and the axonemes maintain their structural integrity. However, with axonemes digested to approximately 80 percent of their initial turbidity, vanadate fails to inhibit the ATP-induced decrease in turbidity and the ATP-induced structural disruption of axonemes, even when the vanadate concentration is raised as high as 100 mum. For such axonemes digested to 80 percent of their initial turbidity, the form of ATP-induced structural changes, in the presence of 25 muM vanadate, was observed by dark-field light microscopy and revealed that the axonemes become disrupted into curved, isolated doublet microtubules, small groups of doublet microtubules, and \"banana peel\" structures in which tubules have peeled back from the axoneme. Addition of 5 muM ATP to rigor wave sperm, which were prepared by abrupt removal of ATP from reactivated sperm, causes straightening of the rigor waves within 1 min, and addition of more than 10 muM ATP causes resumption of flagellar beating. Addition of 40 muM vanadate to the rigor wave sperm does not inhibit straightening of the rigor waves of 2 muM-1 mM ATP, although oscillatory beating is completely inhibited. These results suggest that vanadate inhibits the mechanochemical cycle of dyein at a step subsequent to the MgATP(2-)-induced release of the bridged dynein arms.", "contents": "Study of the mechanism of vanadate inhibition of the dynein cross-bridge cycle in sea urchin sperm flagella. The effect of vanadate on the ATP-induced disruption of trypsin-treated axonemes and the ATP-induced straightening of rigor wave preparations of sea urchin sperm was investigated. Addition of ATP to a suspension of trypsin-treated axonemes results in a rapid decrease in turbidity (optical density measured at 350 nm) concomitant with the disruption of the axonemes by sliding between microtubules to form tangles of connected doublet microtubules (Summers and Gibbons, 1971; Sale and Satir, 1977). For axonemes digested to approximately 93 percent of their initial turbidity, 5 {muM} vanadate completely inhibits the ATP-induced decrease in turbidity and the axonemes maintain their structural integrity. However, with axonemes digested to approximately 80 percent of their initial turbidity, vanadate fails to inhibit the ATP-induced decrease in turbidity and the ATP-induced structural disruption of axonemes, even when the vanadate concentration is raised as high as 100 mum. For such axonemes digested to 80 percent of their initial turbidity, the form of ATP-induced structural changes, in the presence of 25 muM vanadate, was observed by dark-field light microscopy and revealed that the axonemes become disrupted into curved, isolated doublet microtubules, small groups of doublet microtubules, and \"banana peel\" structures in which tubules have peeled back from the axoneme. Addition of 5 muM ATP to rigor wave sperm, which were prepared by abrupt removal of ATP from reactivated sperm, causes straightening of the rigor waves within 1 min, and addition of more than 10 muM ATP causes resumption of flagellar beating. Addition of 40 muM vanadate to the rigor wave sperm does not inhibit straightening of the rigor waves of 2 muM-1 mM ATP, although oscillatory beating is completely inhibited. These results suggest that vanadate inhibits the mechanochemical cycle of dyein at a step subsequent to the MgATP(2-)-induced release of the bridged dynein arms."} {"id": "PMID:158029", "title": "N-ethylmaleimide-modified heavy meromyosin. A probe for actomyosin interactions.", "content": "Treatment of rabbit skeletal muscle heavy meromyosin (HMM) with the sulfhydryl reagent N-ethylmaleimide (NEM) produces a species of HMM which remains tightly bound to actin in the presence of MgATP. NEM-HMM forms characteristic \"arrowhead\" complexes with actin which persist despite rinses with MgATP. NEM-HMM inhibits the actin activation of native HMM-ATPase activity, the superprecipitation of actomyosin, the contraction of glycerinated muscle myofibrils, and the contraction of cytoplasmic strands of the soil amoeba Chaos carolinensis. However, NEM-HMM does not interfere with in vitro microtubule polymerization or beating of demembranated cilia.", "contents": "N-ethylmaleimide-modified heavy meromyosin. A probe for actomyosin interactions. Treatment of rabbit skeletal muscle heavy meromyosin (HMM) with the sulfhydryl reagent N-ethylmaleimide (NEM) produces a species of HMM which remains tightly bound to actin in the presence of MgATP. NEM-HMM forms characteristic \"arrowhead\" complexes with actin which persist despite rinses with MgATP. NEM-HMM inhibits the actin activation of native HMM-ATPase activity, the superprecipitation of actomyosin, the contraction of glycerinated muscle myofibrils, and the contraction of cytoplasmic strands of the soil amoeba Chaos carolinensis. However, NEM-HMM does not interfere with in vitro microtubule polymerization or beating of demembranated cilia."} {"id": "PMID:158026", "title": "Erosion of Dacron graft by atherosclerotic plaque.", "content": "Erosion of a Dacron prosthetic graft used in aortic reconstruction following the intrasaccular resection of an infrarenal abdominal aneurysm resulted in perforation of the graft and the formation of a false aneurysm which ruptured. The pathogenesis and prevention of this problem are discussed.", "contents": "Erosion of Dacron graft by atherosclerotic plaque. Erosion of a Dacron prosthetic graft used in aortic reconstruction following the intrasaccular resection of an infrarenal abdominal aneurysm resulted in perforation of the graft and the formation of a false aneurysm which ruptured. The pathogenesis and prevention of this problem are discussed."} {"id": "PMID:158030", "title": "[Vascular complications of needle biopsy of the liver (author's transl)].", "content": "11 complications were observed in 2,346 cases of needle biopsy (frequency 0.47%) carried out in 1,529 cases under laparoscopy, 527 cases by the intercostal route, and in 290 cases during operation. The symptoms usually appeared early, indicating bleeding. The lesions, isolated or associated were six hemoperitoneums, and 9 hematomas (including 2 subcapsular), 3 intrahepatic (1 FAV), one of the gall bladder, 3 undetermined; 5 patients out of 11 were operated on, 4 out of 11 died. The place of surgical treatment is discussed: one hemoperitoneum led to early surgical operation. An intrahepatic or subscapular hematoma may regress without sequelae. An arteriography after a liver scan should eliminate a major vascular lesion which may eventually require surgery.", "contents": "[Vascular complications of needle biopsy of the liver (author's transl)]. 11 complications were observed in 2,346 cases of needle biopsy (frequency 0.47%) carried out in 1,529 cases under laparoscopy, 527 cases by the intercostal route, and in 290 cases during operation. The symptoms usually appeared early, indicating bleeding. The lesions, isolated or associated were six hemoperitoneums, and 9 hematomas (including 2 subcapsular), 3 intrahepatic (1 FAV), one of the gall bladder, 3 undetermined; 5 patients out of 11 were operated on, 4 out of 11 died. The place of surgical treatment is discussed: one hemoperitoneum led to early surgical operation. An intrahepatic or subscapular hematoma may regress without sequelae. An arteriography after a liver scan should eliminate a major vascular lesion which may eventually require surgery."} {"id": "PMID:158032", "title": "Plasma pancreatic hormone levels in a case of somatostatinoma: diagnostic and therapeutic implications.", "content": "Plasma somatostatin immunoreactivity (SIR) was elevated 40-fold in an insulin-treated diabetic with disseminated pancreatic carcinoma. The diagnosis of somatostatinoma was supported by histological and ultrastructural similarities between metastatic cells and pancreatic D cells. Under acid conditions, 75% of the plasma SIR eluted as a 6000- to 7000-dalton protein and 25% as synthetic somatostatin (mol wt 1600), whereas the 20-fold elevated urine SIR consisted almost exclusively of the higher molecular weight fraction. The hypersomatostatinemia was associated with reduced basal and stimulated pancreatic hormone levels, which might reflect its involvement in the steatorrhea and diabetes, and its protection against ketoacidosis. Plasma SIR rose 50% upon insulin withdrawal and 10-fold after tolbutamide injection and fell 30% after diazoxide. It is concluded that an increase in plasma and urine SIR, the presence of a 6000- to 7000-dalton SIR fraction in plasma and urine, a reduction in basal and stimulated pancreatic hormone levels, and tolbutamide-induced somatostatin release can be diagnostic for a somatostatinoma. Streptozotocin reduced tumor volume, hypersomatostatinemia, and tolbutamide-induced somatostatin release, suggesting that this drug may be useful in the treatment of disseminated somatostatinoma.", "contents": "Plasma pancreatic hormone levels in a case of somatostatinoma: diagnostic and therapeutic implications. Plasma somatostatin immunoreactivity (SIR) was elevated 40-fold in an insulin-treated diabetic with disseminated pancreatic carcinoma. The diagnosis of somatostatinoma was supported by histological and ultrastructural similarities between metastatic cells and pancreatic D cells. Under acid conditions, 75% of the plasma SIR eluted as a 6000- to 7000-dalton protein and 25% as synthetic somatostatin (mol wt 1600), whereas the 20-fold elevated urine SIR consisted almost exclusively of the higher molecular weight fraction. The hypersomatostatinemia was associated with reduced basal and stimulated pancreatic hormone levels, which might reflect its involvement in the steatorrhea and diabetes, and its protection against ketoacidosis. Plasma SIR rose 50% upon insulin withdrawal and 10-fold after tolbutamide injection and fell 30% after diazoxide. It is concluded that an increase in plasma and urine SIR, the presence of a 6000- to 7000-dalton SIR fraction in plasma and urine, a reduction in basal and stimulated pancreatic hormone levels, and tolbutamide-induced somatostatin release can be diagnostic for a somatostatinoma. Streptozotocin reduced tumor volume, hypersomatostatinemia, and tolbutamide-induced somatostatin release, suggesting that this drug may be useful in the treatment of disseminated somatostatinoma."} {"id": "PMID:158033", "title": "Chlorozotocin. Mechanism of reduced bone marrow toxicity in mice.", "content": "Chlorozotocin is a chloroethyl nitrosourea with a glucose carrier that has curative activity for the murine L1210 leukemia, but is nonmyelosuppressive in mice. To determine the mechanism for this unique property of reduced bone marrow toxicity, comparative studies were conducted with chlorozotocin and CCNU, a myelotoxic chloroethyl nitrosourea. Suspensions of L1210 leukemia and murine bone marrow cells were incubated for 2 h with 0.1 mM [(14)C]-chloroethyl chlorozotocin or CCNU. Chlorozotocin demonstrated a fourfold increased covalent binding of the chloroethyl group to L1210 nuclei when compared to equimolar CCNU. Chlorozotocin alkylation of L1210 cells resulted in the binding of 57 pmol of [(14)C]ethyl group/mg of DNA, which represented a 2.3-fold increased alkylation when compared to CCNU. In marked contrast, the binding of the chloroethyl group to bone marrow nuclei was equivalent for both drugs. In addition, chlorozotocin alkylation of murine bone marrow DNA, 45 pmol of [(14)C]ethyl group/mg of DNA, was equivalent to that of CCNU. The ratio of L1210:bone marrow DNA alkylation was 1.3 for chlorozotocin compared to 0.6 for CCNU. The intracellular carbamoylation of L1210 and bone marrow protein by CCNU was 400- to 600-fold greater than that produced by chlorozotocin. After a 2-h exposure to 0.1, 0.05, or 0.01 mM drug, both chlorozotocin and CCNU produced a reduction in the cloning efficiency of L1210 cells that was dose dependent. However, chlorozotocin was significantly more cytotoxic than CCNU at all three molar concentrations (P < 0.01). Chlorozotocin, 0.1 mM, reduced L1210 DNA synthesis to 1% of control by 48 h, in contrast to 16% with equimolar CCNU (P < 0.01). In mice bearing 10(5) L1210 cells, chlorozotocin produced its optimal antitumor activity (332% increased life span [ILS]) at doses of 48-64 mumol/kg, with >50% indefinite survivors. In contrast, CCNU at the same molar doses resulted in only a 191% ILS; a CCNU dose of 128 mumol/kg was required for comparable optimal L1210 antitumor activity, 413% ILS. On a molar basis, the dose of chlorozotocin that produced optimal in vivo L1210 antitumor activity was one-third to one-half that of CCNU. Chlorozotocin, unlike CCNU, produced no murine bone marrow toxicity at its optimal therapeutic dose. This unique combination of antitumor activity without myelosuppression can be correlated with the advantageous ratio of L1210:bone marrow in vitro DNA alkylation by chlorozotocin (1.3) as compared to equimolar CCNU (0.6).", "contents": "Chlorozotocin. Mechanism of reduced bone marrow toxicity in mice. Chlorozotocin is a chloroethyl nitrosourea with a glucose carrier that has curative activity for the murine L1210 leukemia, but is nonmyelosuppressive in mice. To determine the mechanism for this unique property of reduced bone marrow toxicity, comparative studies were conducted with chlorozotocin and CCNU, a myelotoxic chloroethyl nitrosourea. Suspensions of L1210 leukemia and murine bone marrow cells were incubated for 2 h with 0.1 mM [(14)C]-chloroethyl chlorozotocin or CCNU. Chlorozotocin demonstrated a fourfold increased covalent binding of the chloroethyl group to L1210 nuclei when compared to equimolar CCNU. Chlorozotocin alkylation of L1210 cells resulted in the binding of 57 pmol of [(14)C]ethyl group/mg of DNA, which represented a 2.3-fold increased alkylation when compared to CCNU. In marked contrast, the binding of the chloroethyl group to bone marrow nuclei was equivalent for both drugs. In addition, chlorozotocin alkylation of murine bone marrow DNA, 45 pmol of [(14)C]ethyl group/mg of DNA, was equivalent to that of CCNU. The ratio of L1210:bone marrow DNA alkylation was 1.3 for chlorozotocin compared to 0.6 for CCNU. The intracellular carbamoylation of L1210 and bone marrow protein by CCNU was 400- to 600-fold greater than that produced by chlorozotocin. After a 2-h exposure to 0.1, 0.05, or 0.01 mM drug, both chlorozotocin and CCNU produced a reduction in the cloning efficiency of L1210 cells that was dose dependent. However, chlorozotocin was significantly more cytotoxic than CCNU at all three molar concentrations (P < 0.01). Chlorozotocin, 0.1 mM, reduced L1210 DNA synthesis to 1% of control by 48 h, in contrast to 16% with equimolar CCNU (P < 0.01). In mice bearing 10(5) L1210 cells, chlorozotocin produced its optimal antitumor activity (332% increased life span [ILS]) at doses of 48-64 mumol/kg, with >50% indefinite survivors. In contrast, CCNU at the same molar doses resulted in only a 191% ILS; a CCNU dose of 128 mumol/kg was required for comparable optimal L1210 antitumor activity, 413% ILS. On a molar basis, the dose of chlorozotocin that produced optimal in vivo L1210 antitumor activity was one-third to one-half that of CCNU. Chlorozotocin, unlike CCNU, produced no murine bone marrow toxicity at its optimal therapeutic dose. This unique combination of antitumor activity without myelosuppression can be correlated with the advantageous ratio of L1210:bone marrow in vitro DNA alkylation by chlorozotocin (1.3) as compared to equimolar CCNU (0.6)."} {"id": "PMID:158034", "title": "Studies of human cord blood and adult lymphocyte interactions with in vitro immunoglobulin production.", "content": "Newborns are unable to produce normal amounts of immunoglobulin despite the presence of circulating lymphocytes with surface immunoglobin (Ig). This study was designed to examine the cellular basis of such impaired Ig synthesis in the newborn infant. An in vitro assay for IgG and IgM synthesis was employed which measured the Ig present in the supernates of pokeweed mitogen-stimulated cord blood and/or adult peripheral mononuclear cells (MNC). Results were as follows: (a) the addition of cord blood MNC to adult MNC suppressed both normal IgG and IgM production; (b) addition of a suspension of adult thymus-derived (T) cells to cord bone marrow-derived (B) cells did not enhance the production of Ig; (c) the addition of cord T cells to adult B cells did not enhance normal Ig production but did significantly depress IgM and IgG synthesis; and (d) irradiation of cord T cells with 2,000 rads removed the suppressive effect of cord T cells on adult MNC. A similar reversal of the suppressive effect exerted by cord MNC was also seen in the presence of 10 microM of hydrocortisone. It appears that the inability of newborn infants to make normal amounts of Ig is a result of a combined B-cell defect and the presence of a steroid-sensitive and radiosensitive suppressor cord T cell.", "contents": "Studies of human cord blood and adult lymphocyte interactions with in vitro immunoglobulin production. Newborns are unable to produce normal amounts of immunoglobulin despite the presence of circulating lymphocytes with surface immunoglobin (Ig). This study was designed to examine the cellular basis of such impaired Ig synthesis in the newborn infant. An in vitro assay for IgG and IgM synthesis was employed which measured the Ig present in the supernates of pokeweed mitogen-stimulated cord blood and/or adult peripheral mononuclear cells (MNC). Results were as follows: (a) the addition of cord blood MNC to adult MNC suppressed both normal IgG and IgM production; (b) addition of a suspension of adult thymus-derived (T) cells to cord bone marrow-derived (B) cells did not enhance the production of Ig; (c) the addition of cord T cells to adult B cells did not enhance normal Ig production but did significantly depress IgM and IgG synthesis; and (d) irradiation of cord T cells with 2,000 rads removed the suppressive effect of cord T cells on adult MNC. A similar reversal of the suppressive effect exerted by cord MNC was also seen in the presence of 10 microM of hydrocortisone. It appears that the inability of newborn infants to make normal amounts of Ig is a result of a combined B-cell defect and the presence of a steroid-sensitive and radiosensitive suppressor cord T cell."} {"id": "PMID:158035", "title": "Streptozotocin (NSC-85998) in children with acute lymphocytic leukemia. A Southwest Oncology Group study.", "content": "Streptozotocin (NSC-85998), a nitrosourea antibiotic, was given to 18 children with acute lymphocytic leukemia in relapse in a dose of 500 mg/m2/day intravenously every day for five days. There were no responses in 14 fully evaluable patients. The principal toxicity consisted of gastrointestinal disturbances. Based on our findings and those of others in adults, steptozotocin appears to play no role in the management of acute lymphocytic leukemia.", "contents": "Streptozotocin (NSC-85998) in children with acute lymphocytic leukemia. A Southwest Oncology Group study. Streptozotocin (NSC-85998), a nitrosourea antibiotic, was given to 18 children with acute lymphocytic leukemia in relapse in a dose of 500 mg/m2/day intravenously every day for five days. There were no responses in 14 fully evaluable patients. The principal toxicity consisted of gastrointestinal disturbances. Based on our findings and those of others in adults, steptozotocin appears to play no role in the management of acute lymphocytic leukemia."} {"id": "PMID:158043", "title": "Endodontists: a manpower projection.", "content": "Since endodontics was first recognized as a specialty of dental practice in 1963, numerous postdoctoral programs have been established or expanded to meet a growing demand for endodontic manpower. There is evidence that a serious threat of overproduction now exists. Projections of active dentist and endodontist populations provide a basis for adjusting endodontic program size.", "contents": "Endodontists: a manpower projection. Since endodontics was first recognized as a specialty of dental practice in 1963, numerous postdoctoral programs have been established or expanded to meet a growing demand for endodontic manpower. There is evidence that a serious threat of overproduction now exists. Projections of active dentist and endodontist populations provide a basis for adjusting endodontic program size."} {"id": "PMID:158045", "title": "The impact of a curriculum change on student attitude and ultimate professional behavior.", "content": "The longitudinal effects of curriculum changes on student attitude and the relationship between attitudes as students and behavior as a professionals in practice are explored in this paper. A curriculum change (treatment of handicapped patients) was planned, introduced, and its effects on student attitude and professional behavior monitored. Findings indicate that: (1) exposure to handicapping conditions significantly lowered student humanitarian attitudes about the treatment of handicapped patients, (2) involvement with handicapped, regardless of the type of involvement (i.e. clinical or supervising oral hygiene care), appears to adversely affect humanitarian attitudes of students regarding handicapped patients. (3) student estimation of their future behavior is not a reliable indication of their future behavior, and (4) changes in curriculum should not be evaluated from student attitudes alone.", "contents": "The impact of a curriculum change on student attitude and ultimate professional behavior. The longitudinal effects of curriculum changes on student attitude and the relationship between attitudes as students and behavior as a professionals in practice are explored in this paper. A curriculum change (treatment of handicapped patients) was planned, introduced, and its effects on student attitude and professional behavior monitored. Findings indicate that: (1) exposure to handicapping conditions significantly lowered student humanitarian attitudes about the treatment of handicapped patients, (2) involvement with handicapped, regardless of the type of involvement (i.e. clinical or supervising oral hygiene care), appears to adversely affect humanitarian attitudes of students regarding handicapped patients. (3) student estimation of their future behavior is not a reliable indication of their future behavior, and (4) changes in curriculum should not be evaluated from student attitudes alone."} {"id": "PMID:158038", "title": "Analysis of an appliance therapy program in a dental school pedodontic clinic.", "content": "It is evident from the data assembled in this paper that a program of appliance therapy in the pedodontic department of a dental school can provide valuable clinical experience for students and benefits for a high percentage of the children who are treated. It is clear that selection of cases, faculty supervision, diagnosis, patient cooperation, and administrative control of patient assignment are the key to a successful program.", "contents": "Analysis of an appliance therapy program in a dental school pedodontic clinic. It is evident from the data assembled in this paper that a program of appliance therapy in the pedodontic department of a dental school can provide valuable clinical experience for students and benefits for a high percentage of the children who are treated. It is clear that selection of cases, faculty supervision, diagnosis, patient cooperation, and administrative control of patient assignment are the key to a successful program."} {"id": "PMID:158046", "title": "A pilot study using remote broadcasting equipment to provide instruction in pedodontics.", "content": "This study investigates the value of remote broadcasting equipment in instruction in pedodontics. Twenty students, between their junior and senior years, were randomly chosen and videotaped during an operative dentistry appointment with a child. Ten students reviewed and critiqued their own tapes immediately after the clinic session. Ten students received instruction using remote broadcasting equipment in an attempt to provide cues and immediate feedback. Results indicate the usefulness of remote broadcasting equipment as a new pedagogic technique in pedodontics.", "contents": "A pilot study using remote broadcasting equipment to provide instruction in pedodontics. This study investigates the value of remote broadcasting equipment in instruction in pedodontics. Twenty students, between their junior and senior years, were randomly chosen and videotaped during an operative dentistry appointment with a child. Ten students reviewed and critiqued their own tapes immediately after the clinic session. Ten students received instruction using remote broadcasting equipment in an attempt to provide cues and immediate feedback. Results indicate the usefulness of remote broadcasting equipment as a new pedagogic technique in pedodontics."} {"id": "PMID:158047", "title": "Genetic knowledge possessed by American nurses and nursing students.", "content": "As diseases of genetic origin have increased their impact on society's health, nursing's role has also increased. Nurses may not be referring those needing it for genetic counselling or prenatal diagnosis and may be inadvertently giving patients erroneous information based on lack of knowledge. A questionnaire was used to examine the overall adequacy and specific knowledge in the more commonly encountered genetic disorders such as sickle cell disease, Rh disease and Down's syndrome. It also included interpretation of risk and basic knowledge. The sample consisted of 366 senior nursing students and 114 practising nurses. Student programme type was consistently related to score. Age was also important in the degree of knowledge manifested. Only 19 (4.2%) of the respondents demonstrated over-all adequate knowledge. These results indicate a need to raise the consciousness and knowledge of nurses about human genetic disorders before serious repercussions result from inappropriate and inadequate counselling, health teaching and referrals.", "contents": "Genetic knowledge possessed by American nurses and nursing students. As diseases of genetic origin have increased their impact on society's health, nursing's role has also increased. Nurses may not be referring those needing it for genetic counselling or prenatal diagnosis and may be inadvertently giving patients erroneous information based on lack of knowledge. A questionnaire was used to examine the overall adequacy and specific knowledge in the more commonly encountered genetic disorders such as sickle cell disease, Rh disease and Down's syndrome. It also included interpretation of risk and basic knowledge. The sample consisted of 366 senior nursing students and 114 practising nurses. Student programme type was consistently related to score. Age was also important in the degree of knowledge manifested. Only 19 (4.2%) of the respondents demonstrated over-all adequate knowledge. These results indicate a need to raise the consciousness and knowledge of nurses about human genetic disorders before serious repercussions result from inappropriate and inadequate counselling, health teaching and referrals."} {"id": "PMID:158048", "title": "The challenge of health education for nurses in the 1980s.", "content": "As nurses are the largest group of health workers, it is argued that their potential for influence, so far as health education is concerned, is very great. The health problems associated with demographic changes in British society, smoking, alcohol, road accidents, dental decay, mental health and the sexual revolution are focused on; and the health education contribution that nurses (and other health workers) can make to alleviate and prevent these problems is discussed. The important role of 'significant others' is also stressed. Problems associated with general lack of basic biological and health information, and with the physically handicapped, and immigrant groups are also noted with concern and are considered to be particular challenges to nurses. Nurses are urged to develop their social skills, to constantly update their knowledge about British society, and to commit themselves to the aims of health education. It is also argued that they need missionary zeal so that they will take health education to the people in the community at large. The basic tenet of the paper is that health education is part and parcel of the nursing process and, therefore, greater involvement of nurses in health education is a logical and rational extension of their role.", "contents": "The challenge of health education for nurses in the 1980s. As nurses are the largest group of health workers, it is argued that their potential for influence, so far as health education is concerned, is very great. The health problems associated with demographic changes in British society, smoking, alcohol, road accidents, dental decay, mental health and the sexual revolution are focused on; and the health education contribution that nurses (and other health workers) can make to alleviate and prevent these problems is discussed. The important role of 'significant others' is also stressed. Problems associated with general lack of basic biological and health information, and with the physically handicapped, and immigrant groups are also noted with concern and are considered to be particular challenges to nurses. Nurses are urged to develop their social skills, to constantly update their knowledge about British society, and to commit themselves to the aims of health education. It is also argued that they need missionary zeal so that they will take health education to the people in the community at large. The basic tenet of the paper is that health education is part and parcel of the nursing process and, therefore, greater involvement of nurses in health education is a logical and rational extension of their role."} {"id": "PMID:158055", "title": "In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma.", "content": "BN rats immunized subcutaneously with a viral induced tumor (MST) or with a chemical-induced fibrosarcoma (BC5) were donors of immune spleen cells. Samples of immune spleen cells were tested in vitro against MST and BC5 in a 51Cr release assay before culturing and after 7 days of culture with mitomycin C-treated MST and/or BC5 tumor cells (MSTMit, BC5Mit). These spleen cells were infused in vivo i.v. into x-rayed (400 R) and nonirradiated BN recipients that bore a vascularized and progressive (1 to 1.5 cm in diameter) subcutaneous MST or BC5. Spleen cells from untreated BN donor rats were also tested in vitro and in vivo as controls. Established MST were specifically eliminated by spleen cells immune to MST after culture with MSTMit, but not by spleen cells immune to MST without further culture nor by cultured or uncultured BC5 immune spleen cells and control spleen cells. Also, the growth of BC5 was not affected by MST immune spleen cells cultured for 7 days with MST and/or BC5. Elimination of Moloney sarcoma (MST) in vivo occurred in less than 35 days and was correlated with the generation of cytotoxicity in vitro since only MST immune spleen cells cultured with MSTMit were able to augment significantly their cytotoxic capability in vitro.", "contents": "In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma. BN rats immunized subcutaneously with a viral induced tumor (MST) or with a chemical-induced fibrosarcoma (BC5) were donors of immune spleen cells. Samples of immune spleen cells were tested in vitro against MST and BC5 in a 51Cr release assay before culturing and after 7 days of culture with mitomycin C-treated MST and/or BC5 tumor cells (MSTMit, BC5Mit). These spleen cells were infused in vivo i.v. into x-rayed (400 R) and nonirradiated BN recipients that bore a vascularized and progressive (1 to 1.5 cm in diameter) subcutaneous MST or BC5. Spleen cells from untreated BN donor rats were also tested in vitro and in vivo as controls. Established MST were specifically eliminated by spleen cells immune to MST after culture with MSTMit, but not by spleen cells immune to MST without further culture nor by cultured or uncultured BC5 immune spleen cells and control spleen cells. Also, the growth of BC5 was not affected by MST immune spleen cells cultured for 7 days with MST and/or BC5. Elimination of Moloney sarcoma (MST) in vivo occurred in less than 35 days and was correlated with the generation of cytotoxicity in vitro since only MST immune spleen cells cultured with MSTMit were able to augment significantly their cytotoxic capability in vitro."} {"id": "PMID:158056", "title": "Lepromin-induced suppressor cells in patients with leprosy.", "content": "The possibility of an active mechanism of immunologic suppression in leprosy was explored by assessing the in vitro lymphocyte responses of 61 leprosy patients and 30 normal individuals to the mitogen Con A in the presence or absence of Dharmendra lepromin. Lepromin-induced suppression of Con A stimulation was found in 32 of 35 lepromatous patients and 15 of 15 borderline patients, but only 2 of 15 tuberculoid patients and 2 of 30 normal controls. Cell fractionation studies indicated at least two cell populations involved in the in vitro lepromin-induced suppressor activity, adherent cells and T gamma-cells.", "contents": "Lepromin-induced suppressor cells in patients with leprosy. The possibility of an active mechanism of immunologic suppression in leprosy was explored by assessing the in vitro lymphocyte responses of 61 leprosy patients and 30 normal individuals to the mitogen Con A in the presence or absence of Dharmendra lepromin. Lepromin-induced suppression of Con A stimulation was found in 32 of 35 lepromatous patients and 15 of 15 borderline patients, but only 2 of 15 tuberculoid patients and 2 of 30 normal controls. Cell fractionation studies indicated at least two cell populations involved in the in vitro lepromin-induced suppressor activity, adherent cells and T gamma-cells."} {"id": "PMID:158057", "title": "Detection of early lymphocyte activation by the fluorescent cell membrane probe N-phenyl-1-naphthylamine.", "content": "N-phenyl-1-naphthylamine (NPN) becomes fluorescent after binding to hydrophobic regions of cell membranes. Rat and mouse lymphoid cell suspensions stained with NPN showed changes in fluorescence emission 30 min after stimulation with mitogen or antigen, detected by microfluorimetry. Incubation of NPN-labelled mouse and rat thymocytes with phytohaemagglutinin or concanavalin A (Con A) caused an increase in mean cell fluorescence intensity. The response to Con A was inhibited by sodium azide and alpha-methyl mannoside. Stimulation of spleen cells from mice by allogeneic cells, or from tumour-bearing rats by tumour antigen consistently resulted in decreased fluorescence. The 'mixed lymphocyte response' detected only certain genetic differences between mouse strains and was proportional to the ratio of stimulator to responder cell number. The NPN staining procedure offers a simple and rapid assay of immunoreactivity and a means of studying early subcellular changes following lymphocyte activation.", "contents": "Detection of early lymphocyte activation by the fluorescent cell membrane probe N-phenyl-1-naphthylamine. N-phenyl-1-naphthylamine (NPN) becomes fluorescent after binding to hydrophobic regions of cell membranes. Rat and mouse lymphoid cell suspensions stained with NPN showed changes in fluorescence emission 30 min after stimulation with mitogen or antigen, detected by microfluorimetry. Incubation of NPN-labelled mouse and rat thymocytes with phytohaemagglutinin or concanavalin A (Con A) caused an increase in mean cell fluorescence intensity. The response to Con A was inhibited by sodium azide and alpha-methyl mannoside. Stimulation of spleen cells from mice by allogeneic cells, or from tumour-bearing rats by tumour antigen consistently resulted in decreased fluorescence. The 'mixed lymphocyte response' detected only certain genetic differences between mouse strains and was proportional to the ratio of stimulator to responder cell number. The NPN staining procedure offers a simple and rapid assay of immunoreactivity and a means of studying early subcellular changes following lymphocyte activation."} {"id": "PMID:158058", "title": "A method for the assay of inflammatory mediators in follicular casts.", "content": "A method is presented whereby inflammatory mediators may be detected and quantified in individual follicular casts. Lysozyme, lactoferrin, IgG, IgM, C3 and material reacting with antiserum to polymorphonuclear leukocytes (PMN) were assayed by functional and immunologic methods. By these techniques, lysozyme, IgG and anti-PMN reactive material were detected in clinically uninflamed follicular casts from acne subjects.", "contents": "A method for the assay of inflammatory mediators in follicular casts. A method is presented whereby inflammatory mediators may be detected and quantified in individual follicular casts. Lysozyme, lactoferrin, IgG, IgM, C3 and material reacting with antiserum to polymorphonuclear leukocytes (PMN) were assayed by functional and immunologic methods. By these techniques, lysozyme, IgG and anti-PMN reactive material were detected in clinically uninflamed follicular casts from acne subjects."} {"id": "PMID:158059", "title": "Serotonin involvement in the control of phasic luteinizing hormone release in the rat: evidence for a critical period.", "content": "A marked surge of luteinizing hormone (LH) occurs daily at 18.00 h in oestrogen-treated ovariectomized rats maintained under regular lighting from 06.00 to 20.00 h. The administration of p-chlorophenylalanine (PCPA),p-chloramphetamine or 5,6-dihydroxytryptamine in treatments designed to cause a severe depletion of brain serotonin abolished this daily surge. Synthesis of serotonin may be temporarily restored in PCPA-treated animals by the administration of the serotonin precursor, 5-hydroxytryptophan. The effectiveness with which restoration of synthesis resulted in restoration of the LH surge varied according to the time at which the precursor was administered, the optimal time being 10.00 h. The results suggest that there is an essential, permissive function performed by serotonin in the production of the LH surge and that this function occurs during a critical period.", "contents": "Serotonin involvement in the control of phasic luteinizing hormone release in the rat: evidence for a critical period. A marked surge of luteinizing hormone (LH) occurs daily at 18.00 h in oestrogen-treated ovariectomized rats maintained under regular lighting from 06.00 to 20.00 h. The administration of p-chlorophenylalanine (PCPA),p-chloramphetamine or 5,6-dihydroxytryptamine in treatments designed to cause a severe depletion of brain serotonin abolished this daily surge. Synthesis of serotonin may be temporarily restored in PCPA-treated animals by the administration of the serotonin precursor, 5-hydroxytryptophan. The effectiveness with which restoration of synthesis resulted in restoration of the LH surge varied according to the time at which the precursor was administered, the optimal time being 10.00 h. The results suggest that there is an essential, permissive function performed by serotonin in the production of the LH surge and that this function occurs during a critical period."} {"id": "PMID:158061", "title": "Low back pain in family practice: a case control study.", "content": "Eighty-three women between the ages of 25 and 44 years who presented with low back pain during a one-year period were compared with a control group of women matched by age and socioeconomic status. The patients with low back pain presented a larger number of problems to their family physicians during the course of the year, but there were no significant differences noted in the prevalence of symptoms of anxiety and depression during their visits, or in the number of psychological problems presented by the two groups, or in the number of psychoactive medications received for problems other than low back pain. The results suggest that low back pain patients may represent a group who more readily present their symptoms to physicians but that they are no more likely to have psychological problems than similar patients who do not have low back pain.", "contents": "Low back pain in family practice: a case control study. Eighty-three women between the ages of 25 and 44 years who presented with low back pain during a one-year period were compared with a control group of women matched by age and socioeconomic status. The patients with low back pain presented a larger number of problems to their family physicians during the course of the year, but there were no significant differences noted in the prevalence of symptoms of anxiety and depression during their visits, or in the number of psychological problems presented by the two groups, or in the number of psychoactive medications received for problems other than low back pain. The results suggest that low back pain patients may represent a group who more readily present their symptoms to physicians but that they are no more likely to have psychological problems than similar patients who do not have low back pain."} {"id": "PMID:158060", "title": "The induction of hapten-specific immunological tolerance and immunity in B lymphocytes. VI. Differential tolerance susceptibility in adult spleen as a function of B-cell maturation level.", "content": "The maturation level of the B-lymphocyte subpopulations involved in trinitrophenyl (TNP)-specific immunological tolerance in adult mice induced by the injection of trinitrobenzenesulfonic acid (TNBS) was investigated using in vitro antigen-specific and nonspecific polyclonal stimulation. The maturity of the B-cell subsets being studied was defined by the antigen or polyclonal activator which evoked a response. Thus, the thymic independent (TI-1) antigen TNP-lipopolysaccharide (TNP-LPS) and the polyclonal stimulant LPS were used to activate immature, neonatal-type B lymphocytes, whereas mature, adult-type B cells were responsive to the TI-2 antigen, TNP-Ficoll, and the nonspecific activator, purified protein derivative (PPD). Whereas unresponsiveness in TNP-LPS-reactive (immature) B cells 4 d after TNBS treatment was previously shown to be the result of functional deletion, partially reversible receptor blockade was detected in this study early after tolerogen treatment. By the 24-h point, tolerance was irreversible, as assessed by 24-h of antigen-free incubation and cocultivation of tolerant cells with control splenocytes. Tolerance was induced more rapidly in immature, TI-1 B cells than in mature TI-2 B lymphocytes. B lymphocytes reactive to TNP-Ficoll were also less susceptible to receptor blockade. Using LPS as a nonspecific probe for immature B cells, 60% tolerance in high affinity TNP-specific cells was induced within 12 h of TNBS treatment, and complete unresponsiveness by 24 h. In contrast, no significant decrease in response to the mature B-cell activator, PPD, occurred until day 2. Furthermore, the 50% tolerance level was achieved in TNP-specific LPS-reactive B cells by 100 times less tolerogen than required for PPD-responsive cells. Thus, TNBS-induced unresponsiveness in cells reactive to TNP-LPS is initially a result of reversible receptor blockade which leads within 4 d to functional deletion. Immature, TI-1 B lymphocytes, which give polyclonal responses to LPS and antigen-specific responses to TNP-LPS, are rendered tolerant to TNBS more rapidly and at lower tolerogen does than mature, TI-2 mouse B cells which react polyclonally to PPD and specifically to TNP-Ficoll. Moreover, these data show that both the immature and the mature B lymphocyts with these characteristic tolerance susceptibilities and specific and nonspecific immune response patterns are present in the adult mouse spleen.", "contents": "The induction of hapten-specific immunological tolerance and immunity in B lymphocytes. VI. Differential tolerance susceptibility in adult spleen as a function of B-cell maturation level. The maturation level of the B-lymphocyte subpopulations involved in trinitrophenyl (TNP)-specific immunological tolerance in adult mice induced by the injection of trinitrobenzenesulfonic acid (TNBS) was investigated using in vitro antigen-specific and nonspecific polyclonal stimulation. The maturity of the B-cell subsets being studied was defined by the antigen or polyclonal activator which evoked a response. Thus, the thymic independent (TI-1) antigen TNP-lipopolysaccharide (TNP-LPS) and the polyclonal stimulant LPS were used to activate immature, neonatal-type B lymphocytes, whereas mature, adult-type B cells were responsive to the TI-2 antigen, TNP-Ficoll, and the nonspecific activator, purified protein derivative (PPD). Whereas unresponsiveness in TNP-LPS-reactive (immature) B cells 4 d after TNBS treatment was previously shown to be the result of functional deletion, partially reversible receptor blockade was detected in this study early after tolerogen treatment. By the 24-h point, tolerance was irreversible, as assessed by 24-h of antigen-free incubation and cocultivation of tolerant cells with control splenocytes. Tolerance was induced more rapidly in immature, TI-1 B cells than in mature TI-2 B lymphocytes. B lymphocytes reactive to TNP-Ficoll were also less susceptible to receptor blockade. Using LPS as a nonspecific probe for immature B cells, 60% tolerance in high affinity TNP-specific cells was induced within 12 h of TNBS treatment, and complete unresponsiveness by 24 h. In contrast, no significant decrease in response to the mature B-cell activator, PPD, occurred until day 2. Furthermore, the 50% tolerance level was achieved in TNP-specific LPS-reactive B cells by 100 times less tolerogen than required for PPD-responsive cells. Thus, TNBS-induced unresponsiveness in cells reactive to TNP-LPS is initially a result of reversible receptor blockade which leads within 4 d to functional deletion. Immature, TI-1 B lymphocytes, which give polyclonal responses to LPS and antigen-specific responses to TNP-LPS, are rendered tolerant to TNBS more rapidly and at lower tolerogen does than mature, TI-2 mouse B cells which react polyclonally to PPD and specifically to TNP-Ficoll. Moreover, these data show that both the immature and the mature B lymphocyts with these characteristic tolerance susceptibilities and specific and nonspecific immune response patterns are present in the adult mouse spleen."} {"id": "PMID:158068", "title": "Characterization of Ca2+-ATPase activity in Streptomyces griseus.", "content": "Ca2+-ATPase activity has been characterized in Streptomyces griseus. The enzyme has a pH optimum of 8.5 at 37 degrees C. Its Ca2+ requirement can be substituted by Cd2+, Zn2+ and Mn2+. Mg2+ inhibits the enzyme non-competitively.", "contents": "Characterization of Ca2+-ATPase activity in Streptomyces griseus. Ca2+-ATPase activity has been characterized in Streptomyces griseus. The enzyme has a pH optimum of 8.5 at 37 degrees C. Its Ca2+ requirement can be substituted by Cd2+, Zn2+ and Mn2+. Mg2+ inhibits the enzyme non-competitively."} {"id": "PMID:158069", "title": "Coliphage lambda ghosts obtained by osmotic shock or LiCl treatment are devoid of J- and H-gene products.", "content": "We have proved by acrylamide gel electrophoresis that DNA-free ghosts of bacteriophage lambda obtained by osmotic shock (S-ghosts), or by incubation in 5 M-L-Cl (L-ghosts) do not possess the proteins specified by the genes J and H. Electron microscopy of L-ghosts showed that they are devoid of the whole tail tip, composed of the basal part and the tail fibre. The lack of the J-gene product, which is believed to be the tail fibre, explains why S- and L-ghosts do not adsorb to susceptible bacteria. Our results suggest that the H-gene product, which is modified after translation, is situated in the basal part of the tail.", "contents": "Coliphage lambda ghosts obtained by osmotic shock or LiCl treatment are devoid of J- and H-gene products. We have proved by acrylamide gel electrophoresis that DNA-free ghosts of bacteriophage lambda obtained by osmotic shock (S-ghosts), or by incubation in 5 M-L-Cl (L-ghosts) do not possess the proteins specified by the genes J and H. Electron microscopy of L-ghosts showed that they are devoid of the whole tail tip, composed of the basal part and the tail fibre. The lack of the J-gene product, which is believed to be the tail fibre, explains why S- and L-ghosts do not adsorb to susceptible bacteria. Our results suggest that the H-gene product, which is modified after translation, is situated in the basal part of the tail."} {"id": "PMID:158071", "title": "Ultrastructural localization of monoamines in nerve fibers of the pineal gland in golden hamsters.", "content": "Nerve terminals in the pineal glands of control, parachlorophenylalanine (PCPA)-, reserpine- and nialamide-administered hamsters were studied with glutaraldehyde-dichromate (GD) and formaldehyde-glutaraldehyde-dichromate (FGD) techniques in the electron microscope. In control pineals treated with the FGD or GD technique, clusters of electron dense reactive particles with a diameter of 20-30 nm, and mainly located in the perivascular space, were identified as dense cores of the small granulated vesicles (SGVs) in the pineal nerve fibers. After the administration of PCPA, the reactive cores were greatly decreased in number in the FGD-treated pineal blocks, whereas a lot of clusters of reactive cores were observed in the perivascular space in GD-treated specimens. After reserpine treatment, no reactive structures were revealed by GD or FGD technique. Reactive cores appeared to be increased in number and in electron density in GD- or FGD-treated pineals of hamsters after administration of nialamide. From the observations, it is concluded that the dense cores of SGVs in the pineal nerve fibers contain both primary catecholamines and 5-hydroxytryptamine although it was not determined whether both amines are located in the same or separate vesicles.", "contents": "Ultrastructural localization of monoamines in nerve fibers of the pineal gland in golden hamsters. Nerve terminals in the pineal glands of control, parachlorophenylalanine (PCPA)-, reserpine- and nialamide-administered hamsters were studied with glutaraldehyde-dichromate (GD) and formaldehyde-glutaraldehyde-dichromate (FGD) techniques in the electron microscope. In control pineals treated with the FGD or GD technique, clusters of electron dense reactive particles with a diameter of 20-30 nm, and mainly located in the perivascular space, were identified as dense cores of the small granulated vesicles (SGVs) in the pineal nerve fibers. After the administration of PCPA, the reactive cores were greatly decreased in number in the FGD-treated pineal blocks, whereas a lot of clusters of reactive cores were observed in the perivascular space in GD-treated specimens. After reserpine treatment, no reactive structures were revealed by GD or FGD technique. Reactive cores appeared to be increased in number and in electron density in GD- or FGD-treated pineals of hamsters after administration of nialamide. From the observations, it is concluded that the dense cores of SGVs in the pineal nerve fibers contain both primary catecholamines and 5-hydroxytryptamine although it was not determined whether both amines are located in the same or separate vesicles."} {"id": "PMID:158074", "title": "Oculomotor disorders in Huntington's chorea.", "content": "Electro-oculographic recordings were obtained from 11 patients with Huntington's disease. Significant reduction of saccadic velocity was constantly found. In all the patients vertical saccades were much more impaired than horizontal. When present, vertical saccades showed long latency, low amplitude, low velocity, and disturbances related to blinking. Following movements were jerky, and ability to perform repeated rhythmic movements was impaired. These results are in agreement with previous observations and underline the selective defect of rapid movements as a characteristic feature of Huntington's disease. Further, they suggest a possible correlation between the difficulty in performing repeated ocular movements and the impaired execution of gestural sequences involving a succession of different fundamental movements.", "contents": "Oculomotor disorders in Huntington's chorea. Electro-oculographic recordings were obtained from 11 patients with Huntington's disease. Significant reduction of saccadic velocity was constantly found. In all the patients vertical saccades were much more impaired than horizontal. When present, vertical saccades showed long latency, low amplitude, low velocity, and disturbances related to blinking. Following movements were jerky, and ability to perform repeated rhythmic movements was impaired. These results are in agreement with previous observations and underline the selective defect of rapid movements as a characteristic feature of Huntington's disease. Further, they suggest a possible correlation between the difficulty in performing repeated ocular movements and the impaired execution of gestural sequences involving a succession of different fundamental movements."} {"id": "PMID:158076", "title": "Quantitative studies of the mutagenesis of Toxoplasma gondii.", "content": "The induction of mutants resistant to 5-fluorodeoxyuridine (FUDR) was used to measure the efficiency of various physical and chemical mutagens on extracellular and intracellular Toxoplasma gondii. The frequency of resistant mutant was measured by plaque assay in human fibroblast cultures in the presence and absence of FUDR. When considered as a function of lethality, the most efficient mutagenesis was obtained with nitrosoguanidine treatment of extracellular parasites and with ethylmethane sulfonate treatment of actively growing intracellular parasites. Each of these treatments increased the frequency of FUDR-resistant mutants from less than one to more than 200 per million parasites. Ultraviolet irradiation, X-rays, and the alkylating mustard ICR-191 also induced FUDR-resistant mutants in a dose-dependent fashion.", "contents": "Quantitative studies of the mutagenesis of Toxoplasma gondii. The induction of mutants resistant to 5-fluorodeoxyuridine (FUDR) was used to measure the efficiency of various physical and chemical mutagens on extracellular and intracellular Toxoplasma gondii. The frequency of resistant mutant was measured by plaque assay in human fibroblast cultures in the presence and absence of FUDR. When considered as a function of lethality, the most efficient mutagenesis was obtained with nitrosoguanidine treatment of extracellular parasites and with ethylmethane sulfonate treatment of actively growing intracellular parasites. Each of these treatments increased the frequency of FUDR-resistant mutants from less than one to more than 200 per million parasites. Ultraviolet irradiation, X-rays, and the alkylating mustard ICR-191 also induced FUDR-resistant mutants in a dose-dependent fashion."} {"id": "PMID:158077", "title": "Use of Teflon mesh for repair of abdominal wall defects in neonates.", "content": "Since 1975, we have employed Teflon mesh sutured to the fascial rim in four newborns with giant omphaloceles, with approximation of skin flaps over the mesh. By stabilizing the anterior abdominal wall, the Teflon mesh has prevented formation of large ventral hernias. The mesh has been retained in place for a year or longer, until the growth of the child permits excision of the prosthesis and fascial approximation without difficulty. A similar technique has been successfully employed in a fifth neonate following transabdominal correction of congenital bilateral eventration of the diaphragm to avoid unacceptable increase in intra-abdominal pressure with primary closure of the abdominal wall. The Teflon mesh appears ideally suited for this technique. It is well incorporated into the fascial rim with minimal foreign body reaction. At the time of secondary repair, the mesh can easily excised from the smooth underlying pseudomembrane covering the bowel. All infants achieved stable abdominal walls by this technique. Three patients have undergone excision of the Teflon mesh and fascial repair at 12, 15, and 36 mo of age without difficulty.", "contents": "Use of Teflon mesh for repair of abdominal wall defects in neonates. Since 1975, we have employed Teflon mesh sutured to the fascial rim in four newborns with giant omphaloceles, with approximation of skin flaps over the mesh. By stabilizing the anterior abdominal wall, the Teflon mesh has prevented formation of large ventral hernias. The mesh has been retained in place for a year or longer, until the growth of the child permits excision of the prosthesis and fascial approximation without difficulty. A similar technique has been successfully employed in a fifth neonate following transabdominal correction of congenital bilateral eventration of the diaphragm to avoid unacceptable increase in intra-abdominal pressure with primary closure of the abdominal wall. The Teflon mesh appears ideally suited for this technique. It is well incorporated into the fascial rim with minimal foreign body reaction. At the time of secondary repair, the mesh can easily excised from the smooth underlying pseudomembrane covering the bowel. All infants achieved stable abdominal walls by this technique. Three patients have undergone excision of the Teflon mesh and fascial repair at 12, 15, and 36 mo of age without difficulty."} {"id": "PMID:158085", "title": "The regularity of muscle spindle discharge in man.", "content": "1. The variability of discharge of thirty-nine muscle spindle afferents from the pretibial muscles of normal human subjects was determined for spike train sequences recorded with the ankle joint fixed in 25 degrees plantar flexion, during further stretch and during graded voluntary contractions of the receptor-bearing muscle. 2. In non-contracting muscles with the ankle joint in 25 degrees plantar flexion, a sustained discharge was maintained by twenty-four of the thirty-nine endings. The mean discharge frequency for the active endings was 11.1 Hz (range 4.8--22.1 Hz), the mean coefficient of variation 0.073 (range 0.021--0.183). With further stretch, the discharge of endings maintaining frequencies below 10--12 Hz became more regular. For endings maintaining higher frequencies, changes in the coefficient of variation were small and occurred in either direction. All secondary endings maintained a highly regular discharge, but, at these frequencies, there was no statistically significant difference in the variability of primary and secondary endings. 3. It is considered that these findings are comparable to those of Matthews & Stein (1969) for de-efferented feline spindle endings, and support the view that there is no functionally effective background fusimotor drive to non-contracting muscles of normal human subjects. 4. A voluntary contraction sufficient to accelerate a spindle ending invariably decreased the regularity of its afferent discharge. During voluntary contractions, coefficients of variation up to 0.345 were recorded. However, coefficients as low as 0.1 were not uncommon, and thus the absence of fusimotor drive cannot necessarily be inferred from a regular afferent discharge pattern. 5. With contractions of different strength, the increase in the coefficient of variation did not parallel the increase in discharge frequency. It is concluded that not all fusimotor influences acting on a spindle ending are translated into variability, and that measurements of the variability of discharge do not accurately reflect the level of fusimotor drive. 6. The discharge frequency of some spindle endings decreased slightly in some contractions and this was accompanied by an increase in the variability of discharge. It is suggested that contracting extrafusal muscle fibres can modulate the discharge pattern of spindle endings and contribute to the variability of discharge during a voluntary contraction. 7. In contracting muscles the irregular fusimotor-driven spindle discharge contained a 'hidden' periodicity, but this was not as extensive as has been reported for the cat. No such periodicity could be demonstrated for spindle endings in non-contracting human muscles.", "contents": "The regularity of muscle spindle discharge in man. 1. The variability of discharge of thirty-nine muscle spindle afferents from the pretibial muscles of normal human subjects was determined for spike train sequences recorded with the ankle joint fixed in 25 degrees plantar flexion, during further stretch and during graded voluntary contractions of the receptor-bearing muscle. 2. In non-contracting muscles with the ankle joint in 25 degrees plantar flexion, a sustained discharge was maintained by twenty-four of the thirty-nine endings. The mean discharge frequency for the active endings was 11.1 Hz (range 4.8--22.1 Hz), the mean coefficient of variation 0.073 (range 0.021--0.183). With further stretch, the discharge of endings maintaining frequencies below 10--12 Hz became more regular. For endings maintaining higher frequencies, changes in the coefficient of variation were small and occurred in either direction. All secondary endings maintained a highly regular discharge, but, at these frequencies, there was no statistically significant difference in the variability of primary and secondary endings. 3. It is considered that these findings are comparable to those of Matthews & Stein (1969) for de-efferented feline spindle endings, and support the view that there is no functionally effective background fusimotor drive to non-contracting muscles of normal human subjects. 4. A voluntary contraction sufficient to accelerate a spindle ending invariably decreased the regularity of its afferent discharge. During voluntary contractions, coefficients of variation up to 0.345 were recorded. However, coefficients as low as 0.1 were not uncommon, and thus the absence of fusimotor drive cannot necessarily be inferred from a regular afferent discharge pattern. 5. With contractions of different strength, the increase in the coefficient of variation did not parallel the increase in discharge frequency. It is concluded that not all fusimotor influences acting on a spindle ending are translated into variability, and that measurements of the variability of discharge do not accurately reflect the level of fusimotor drive. 6. The discharge frequency of some spindle endings decreased slightly in some contractions and this was accompanied by an increase in the variability of discharge. It is suggested that contracting extrafusal muscle fibres can modulate the discharge pattern of spindle endings and contribute to the variability of discharge during a voluntary contraction. 7. In contracting muscles the irregular fusimotor-driven spindle discharge contained a 'hidden' periodicity, but this was not as extensive as has been reported for the cat. No such periodicity could be demonstrated for spindle endings in non-contracting human muscles."} {"id": "PMID:158087", "title": "A precursor role for DHA in a feto-placental unit for oestrogen formation in the mare.", "content": "Plasma levels of total oestrogens and dehydroepiandrosterone (DHA) were measured by radioimmunossay in samples taken from various blood vessels in both maternal and fetal compartments in 11 Pony mates. High concentrations of oestrogens (greater than 100 ng/ml of plasma), expressed as oestrone equivalents, were found in the fetal circulation. On both the fetal and maternal sides, oestrogen concentrations were lower in blood going to than from the placenta. DHA concentrations, on the other hand, were higher in blood flowing to the placenta from the fetus. The fetal gonads were seen as the source of DHA, which was present in remarkably high concentrations (greater than 800 ng/ml of plasma) in venous samples from fetal ovaries and fetal testes. A precursor role in placental oestrogen formation is suggested for DHA secretion by the fetal gonads.", "contents": "A precursor role for DHA in a feto-placental unit for oestrogen formation in the mare. Plasma levels of total oestrogens and dehydroepiandrosterone (DHA) were measured by radioimmunossay in samples taken from various blood vessels in both maternal and fetal compartments in 11 Pony mates. High concentrations of oestrogens (greater than 100 ng/ml of plasma), expressed as oestrone equivalents, were found in the fetal circulation. On both the fetal and maternal sides, oestrogen concentrations were lower in blood going to than from the placenta. DHA concentrations, on the other hand, were higher in blood flowing to the placenta from the fetus. The fetal gonads were seen as the source of DHA, which was present in remarkably high concentrations (greater than 800 ng/ml of plasma) in venous samples from fetal ovaries and fetal testes. A precursor role in placental oestrogen formation is suggested for DHA secretion by the fetal gonads."} {"id": "PMID:158088", "title": "Episodic nature of the delta 4-ene and delta 5-ene steroidogenic pathways and their relationship to the adreno-gonadal axis in stallions.", "content": "Changes in the daily secretory patterns of testosterone and other 17 beta-hydroxyandrogen, total oestrogens and total corticoids were investigated in 7 stallions. Pulsatile fluctuations in plasma hormone levels were found in the serial blood samples collected hourly for 24 h in all animals. The plasma profiles indicated that corticoids, oestrogens and androgens were secreted episodically at all times in stallions. A significant correlation was observed between the precursor and products of delta 4-ene and delta 5-ene pathways and in inverse correlation (r = -0.68; P less than 0.01) was observed between total androgens and total corticoids. The significance of these episodic fluctuations of the major steroid hormones are discussed.", "contents": "Episodic nature of the delta 4-ene and delta 5-ene steroidogenic pathways and their relationship to the adreno-gonadal axis in stallions. Changes in the daily secretory patterns of testosterone and other 17 beta-hydroxyandrogen, total oestrogens and total corticoids were investigated in 7 stallions. Pulsatile fluctuations in plasma hormone levels were found in the serial blood samples collected hourly for 24 h in all animals. The plasma profiles indicated that corticoids, oestrogens and androgens were secreted episodically at all times in stallions. A significant correlation was observed between the precursor and products of delta 4-ene and delta 5-ene pathways and in inverse correlation (r = -0.68; P less than 0.01) was observed between total androgens and total corticoids. The significance of these episodic fluctuations of the major steroid hormones are discussed."} {"id": "PMID:158089", "title": "Clinical interdisciplinary health team care: an educational experiment.", "content": "With increasing concern for teamwork in clinical practice in health care settings, the need to identify the concepts, methods, and learning processes for improving interdisciplinary team skills is apparent. This paper describes patient-centered, clinical-research-demonstration programs for teams of students, preceptors, and faculty members from six disciplines who provided patient care in a long-term rehabilitation setting. The teams were involved in the theory and practice of team-building, including weekly sessions on leadership styles, communication, group decision-making, and team effectiveness assessment. Objective and subjective measurements were administered throughout the program. The results indicate that task-oriented patient care favors the learning of team skills, especially when all levels of administration support and participate in the processes. Question are raised concerning the effect of clinical teams on the quality of patient care, their cost-effectiveness, and the low priority given to teaching interdisciplinary team skills in professional education.", "contents": "Clinical interdisciplinary health team care: an educational experiment. With increasing concern for teamwork in clinical practice in health care settings, the need to identify the concepts, methods, and learning processes for improving interdisciplinary team skills is apparent. This paper describes patient-centered, clinical-research-demonstration programs for teams of students, preceptors, and faculty members from six disciplines who provided patient care in a long-term rehabilitation setting. The teams were involved in the theory and practice of team-building, including weekly sessions on leadership styles, communication, group decision-making, and team effectiveness assessment. Objective and subjective measurements were administered throughout the program. The results indicate that task-oriented patient care favors the learning of team skills, especially when all levels of administration support and participate in the processes. Question are raised concerning the effect of clinical teams on the quality of patient care, their cost-effectiveness, and the low priority given to teaching interdisciplinary team skills in professional education."} {"id": "PMID:158090", "title": "Ca2+ translocation in Ehrlich ascites tumor cells.", "content": "Ca2+ uptake into Ehrlich ascites tumor cells was studied at 0 degrees C in the presence of mitochondrial inhibitors, conditions that minimized complications caused by sequestration of Ca2+ into organelles or by excretion. Under these conditions Ruthenium Red inhibited Ca2+ uptake, but other previously implicated ions, such as Pi or Mg2+, had no effect. Valinomycin either inhibited or slightly stimulated Ca2+ uptake depending on the presence of excess K+ on the outside or inside of the cell, respectively. Nigericin inhibited Ca2+ transport. Based on these data we propose an electrogenic uptake of Ca2+, possibly via a Ca2+/H+ antiport mechanism. The observation that glucose inhibited Ca2+ uptake suggested that in Ehrlich ascites tumor cells an energy-driven Ca2+ expulsion mechanism is operative, similar to that in erythrocytes. Plasma membrane preparations of ascites tumor cells were found to contain a Ca2+-dependent ATPase. These preparations, when incorporated into liposomes in an inside-out orientation, catalyzed an ATP-dependent uptake of Ca2+.", "contents": "Ca2+ translocation in Ehrlich ascites tumor cells. Ca2+ uptake into Ehrlich ascites tumor cells was studied at 0 degrees C in the presence of mitochondrial inhibitors, conditions that minimized complications caused by sequestration of Ca2+ into organelles or by excretion. Under these conditions Ruthenium Red inhibited Ca2+ uptake, but other previously implicated ions, such as Pi or Mg2+, had no effect. Valinomycin either inhibited or slightly stimulated Ca2+ uptake depending on the presence of excess K+ on the outside or inside of the cell, respectively. Nigericin inhibited Ca2+ transport. Based on these data we propose an electrogenic uptake of Ca2+, possibly via a Ca2+/H+ antiport mechanism. The observation that glucose inhibited Ca2+ uptake suggested that in Ehrlich ascites tumor cells an energy-driven Ca2+ expulsion mechanism is operative, similar to that in erythrocytes. Plasma membrane preparations of ascites tumor cells were found to contain a Ca2+-dependent ATPase. These preparations, when incorporated into liposomes in an inside-out orientation, catalyzed an ATP-dependent uptake of Ca2+."} {"id": "PMID:158091", "title": "Comparison of respiratory mortality in the profoundly mentally retarded and in the less retarded.", "content": "Autopsy records of 600 profoundly retarded and 405 less retarded were examined for a thirty-one-year period at Pacific State Hospital. The profoundly retarded were found to have more respiratory infections at autopsy, and more deaths of such infections. Profound retardation was a particularly outstanding risk when in combination with epilepsy, inability to ambulate, and developmental cranial anomalies. Non-infectious respiratory morbidity and mortality are more common in the less retarded, apparently because of their living longer to develop these complications.", "contents": "Comparison of respiratory mortality in the profoundly mentally retarded and in the less retarded. Autopsy records of 600 profoundly retarded and 405 less retarded were examined for a thirty-one-year period at Pacific State Hospital. The profoundly retarded were found to have more respiratory infections at autopsy, and more deaths of such infections. Profound retardation was a particularly outstanding risk when in combination with epilepsy, inability to ambulate, and developmental cranial anomalies. Non-infectious respiratory morbidity and mortality are more common in the less retarded, apparently because of their living longer to develop these complications."} {"id": "PMID:158092", "title": "The EEG and incidence of epilepsy in Down's syndrome.", "content": "In this series of one hundred and twenty-eight adults with Down's syndrome nearly half (i.e. 42.2 per cent) developed a normal EEG. This would appear to bear out the findings of Gregoziades and Pampiglione (1966) that older children with this syndrome tended to have tracings similar to the normal child. The youngest age group of fifteen to twenty-four years developed a normal tracing in 38.9 per cent of cases. The most frequent abnormality was an excess of theta, in keeping with the suggestion of Godinova and Hirai and Izawa that this was due to immaturity. Neither the presence of congenital heart disease nor diabetes nor intercurrent illness appeared to have any effect on the development of seizures. Epilepsy developed at any time during adult life but, not surprisingly, the five cases developing it had shown sharp or paroxysmal activity previously. Two had suffered from fainting attacks. In one, the diagnosis was confirmed later by a typical grand mal seizure and the other by response to anticonvulsants. Neither suffered from congenital heart disease.", "contents": "The EEG and incidence of epilepsy in Down's syndrome. In this series of one hundred and twenty-eight adults with Down's syndrome nearly half (i.e. 42.2 per cent) developed a normal EEG. This would appear to bear out the findings of Gregoziades and Pampiglione (1966) that older children with this syndrome tended to have tracings similar to the normal child. The youngest age group of fifteen to twenty-four years developed a normal tracing in 38.9 per cent of cases. The most frequent abnormality was an excess of theta, in keeping with the suggestion of Godinova and Hirai and Izawa that this was due to immaturity. Neither the presence of congenital heart disease nor diabetes nor intercurrent illness appeared to have any effect on the development of seizures. Epilepsy developed at any time during adult life but, not surprisingly, the five cases developing it had shown sharp or paroxysmal activity previously. Two had suffered from fainting attacks. In one, the diagnosis was confirmed later by a typical grand mal seizure and the other by response to anticonvulsants. Neither suffered from congenital heart disease."} {"id": "PMID:158093", "title": "The effect of early intervention and pre-school stimulus on the development of the Down's syndrome child.", "content": "This paper describes the effect on a group of D.S. children of early and continuous parental counselling together with intensive pre-school stimulation in which the parents were fully involved. The stimulated group is compared with a similar group who developed unaided in their own homes, and with a third group who were institutionalised before their second birthday. Developmental Clinics in East Kent providing the stimulus are described. The effects of social class, parental age and family pattern were noted. The tests used were the Griffiths' Developmental and Stanford-Binet Scales, and the school placement at five years was studied. The results show that the stimulated group score higher on the IQ and DQ tests and particularly on Personal Social and Speech Development. School placement acts as an unbiased measurement of progress, and suggests that they are more easily integrated into the normal community.", "contents": "The effect of early intervention and pre-school stimulus on the development of the Down's syndrome child. This paper describes the effect on a group of D.S. children of early and continuous parental counselling together with intensive pre-school stimulation in which the parents were fully involved. The stimulated group is compared with a similar group who developed unaided in their own homes, and with a third group who were institutionalised before their second birthday. Developmental Clinics in East Kent providing the stimulus are described. The effects of social class, parental age and family pattern were noted. The tests used were the Griffiths' Developmental and Stanford-Binet Scales, and the school placement at five years was studied. The results show that the stimulated group score higher on the IQ and DQ tests and particularly on Personal Social and Speech Development. School placement acts as an unbiased measurement of progress, and suggests that they are more easily integrated into the normal community."} {"id": "PMID:158094", "title": "Discrimination of size, form and order in mongol and other mentally handicapped children.", "content": "136 mongol, 129 non-mongol subnormal and 152 normal children were tested in a series of experiments to determine visual discrimination and perceptual skills in size, form and order. An attempt was made to demonstrate possible differences in strategies and behaviour in the groups, particularly in the mongol group. It was shown that, in spite of contrary impressions arising from results of normal standardised tests, in these three groups matched on M.A., there was no significant difference in performance when extraneous developmental factors were eliminated. The literature relating to this is discussed. There was further support for the existing experimental evidence that poor short-term memory for visual stimuli in terms of size, form and order is a characteristic weakness of subnormal groups. No relationship was found between M.A. and visual perceptual tasks in any group; supporting the theory that perceptual skills develop independently. A peculiar phenomenon was discovered in the mongol group significant enough to warrant further investigation, viz. a distinctive form of perseveration and a related and clearly marked tendency to order reversal. Suggestions are made and possible reasons presented for this, but, at this stage, without experimental backing.", "contents": "Discrimination of size, form and order in mongol and other mentally handicapped children. 136 mongol, 129 non-mongol subnormal and 152 normal children were tested in a series of experiments to determine visual discrimination and perceptual skills in size, form and order. An attempt was made to demonstrate possible differences in strategies and behaviour in the groups, particularly in the mongol group. It was shown that, in spite of contrary impressions arising from results of normal standardised tests, in these three groups matched on M.A., there was no significant difference in performance when extraneous developmental factors were eliminated. The literature relating to this is discussed. There was further support for the existing experimental evidence that poor short-term memory for visual stimuli in terms of size, form and order is a characteristic weakness of subnormal groups. No relationship was found between M.A. and visual perceptual tasks in any group; supporting the theory that perceptual skills develop independently. A peculiar phenomenon was discovered in the mongol group significant enough to warrant further investigation, viz. a distinctive form of perseveration and a related and clearly marked tendency to order reversal. Suggestions are made and possible reasons presented for this, but, at this stage, without experimental backing."} {"id": "PMID:158097", "title": "Analysis of coliphage lambda mutations that affect Q gene activity: puq, byp, and nin5.", "content": "We describe in this paper the isolation and characterization of a class of mutations, designated puq, that allow phage lambda to grow better under conditions that limit the synthesis of the phage Q gene product. These mutations were located between phage genes P and Q, a region of the lambda chromosome containing two gene N-independent mutations, nin5 and byp, that we also show to be puq mutations. Whereas the puq-3 and puq-16 mutations probably map under the nin5 deletion, the byp mutation maps between this deletion and the Q lambda-Q phi 80 crossover point. These mutations likely act by increasing the synthesis of the Q gene product. We demonstrate that the clear-plaque phenotype and reduced lysogenization frequency of byp mutants depend on increased Q gene activity. The significance of these results in understanding how transcription proceeds through the P-Q region of the lambda genome is discussed.", "contents": "Analysis of coliphage lambda mutations that affect Q gene activity: puq, byp, and nin5. We describe in this paper the isolation and characterization of a class of mutations, designated puq, that allow phage lambda to grow better under conditions that limit the synthesis of the phage Q gene product. These mutations were located between phage genes P and Q, a region of the lambda chromosome containing two gene N-independent mutations, nin5 and byp, that we also show to be puq mutations. Whereas the puq-3 and puq-16 mutations probably map under the nin5 deletion, the byp mutation maps between this deletion and the Q lambda-Q phi 80 crossover point. These mutations likely act by increasing the synthesis of the Q gene product. We demonstrate that the clear-plaque phenotype and reduced lysogenization frequency of byp mutants depend on increased Q gene activity. The significance of these results in understanding how transcription proceeds through the P-Q region of the lambda genome is discussed."} {"id": "PMID:158098", "title": "qin101: Promoter mutation which allows the constitutive expression of the late genes.", "content": "We describe the isolation and characterization of a mutant (lambda qin101) which renders lambda growth Q independent. We have shown that this mutation creates a new promoter, located between genes P and Q, which results in the constitutive expression of the entire Q late region.", "contents": "qin101: Promoter mutation which allows the constitutive expression of the late genes. We describe the isolation and characterization of a mutant (lambda qin101) which renders lambda growth Q independent. We have shown that this mutation creates a new promoter, located between genes P and Q, which results in the constitutive expression of the entire Q late region."} {"id": "PMID:158099", "title": "Physical map of bacteriophage BF23 DNA: terminal redundancy and localization of single-chain interruptions.", "content": "The DNA of bacteriophage BF23 possesses two structural features, localized single-chain interruptions and a large terminal repetition, previously described for T5, a closely related virus. As is the case for T5, single-chain interruptions occur with variable frequencies at a small number of fixed sites within one strand of the double-stranded BF23 genome. The sites where interruptions occur with the highest frequencies were napped by an electrophoretic analysis of the single-stranded fragments produced by denaturation of BF23 DNA. The positions of these fragments were determined by degrading BF23 DNA to various extents with lambda exonuclease and observing the relative order with which they were (i) degraded or (ii) released intact from the undenatured duplex. The exact locations of the interruptions were determined from analysis of analogous duplex fragments produced by degrading exonuclease III-treated BF23 DNA with a single-strand-specific endonuclease. BF23 has five principal sites (located at 7.9, 18.7, 32.4, 65.8, and 99.6% from the left end of the DNA) where interruptions occur in most molecules. The principal interruptions in T5 DNA occur at similar positions. The locations of eight secondary interruptions in BF23 DNA were also determined. In general, BF23 DNA has fewer secondary interruptions than t5 dna, although there is at least one location where an interruption occurs with a greater frequency in BF23. The presence of a terminal repetition in BF23 DNA was demonstrated by annealing ligase-repaired molecules that had been partially digested with lambda exonuclease. If the complementary sequences at both ends of the DNA were exposed by exonuclease treatment, the duplex segment that resulted from annealing could be released by digestion with a single-strand-specific endonuclease. This segment was analyzed by agarose gel electrophoresis and found to represent 8.4% of BF23 DNA.", "contents": "Physical map of bacteriophage BF23 DNA: terminal redundancy and localization of single-chain interruptions. The DNA of bacteriophage BF23 possesses two structural features, localized single-chain interruptions and a large terminal repetition, previously described for T5, a closely related virus. As is the case for T5, single-chain interruptions occur with variable frequencies at a small number of fixed sites within one strand of the double-stranded BF23 genome. The sites where interruptions occur with the highest frequencies were napped by an electrophoretic analysis of the single-stranded fragments produced by denaturation of BF23 DNA. The positions of these fragments were determined by degrading BF23 DNA to various extents with lambda exonuclease and observing the relative order with which they were (i) degraded or (ii) released intact from the undenatured duplex. The exact locations of the interruptions were determined from analysis of analogous duplex fragments produced by degrading exonuclease III-treated BF23 DNA with a single-strand-specific endonuclease. BF23 has five principal sites (located at 7.9, 18.7, 32.4, 65.8, and 99.6% from the left end of the DNA) where interruptions occur in most molecules. The principal interruptions in T5 DNA occur at similar positions. The locations of eight secondary interruptions in BF23 DNA were also determined. In general, BF23 DNA has fewer secondary interruptions than t5 dna, although there is at least one location where an interruption occurs with a greater frequency in BF23. The presence of a terminal repetition in BF23 DNA was demonstrated by annealing ligase-repaired molecules that had been partially digested with lambda exonuclease. If the complementary sequences at both ends of the DNA were exposed by exonuclease treatment, the duplex segment that resulted from annealing could be released by digestion with a single-strand-specific endonuclease. This segment was analyzed by agarose gel electrophoresis and found to represent 8.4% of BF23 DNA."} {"id": "PMID:158100", "title": "Experimental infection of white-tailed deer with Elaeophora schneideri.", "content": "An attempt was made to infect fawn and adult white-tailed deer, Odocoileus virginianus, with Elaeophora schneideri. Experimental infection of fawns caused a relative eosinophilia that persisted. Obstruction of a coronary artery caused death of one fawn, and weakness, dyspnea, and locomotor difficulties were observed in another fawn and an adult. Plaque-like lesions were observed grossly in the intimal lining of carotid arteries, and subintimal thickening and proliferation of fibrous tissue in vessel walls were observed microscopically. Nematodes were recovered from 3 of 4 fawns and 0 of 4 adults, suggesting an age-related resistance in older animals. Microfilariae were recovered via facial skin biopsy of a single fawn. This study suggests that white-tailed deer serve as usual hosts for E. schneideri, although the host-parasite relationship may be tenuous.", "contents": "Experimental infection of white-tailed deer with Elaeophora schneideri. An attempt was made to infect fawn and adult white-tailed deer, Odocoileus virginianus, with Elaeophora schneideri. Experimental infection of fawns caused a relative eosinophilia that persisted. Obstruction of a coronary artery caused death of one fawn, and weakness, dyspnea, and locomotor difficulties were observed in another fawn and an adult. Plaque-like lesions were observed grossly in the intimal lining of carotid arteries, and subintimal thickening and proliferation of fibrous tissue in vessel walls were observed microscopically. Nematodes were recovered from 3 of 4 fawns and 0 of 4 adults, suggesting an age-related resistance in older animals. Microfilariae were recovered via facial skin biopsy of a single fawn. This study suggests that white-tailed deer serve as usual hosts for E. schneideri, although the host-parasite relationship may be tenuous."} {"id": "PMID:158104", "title": "[Therapy of acute keratoconus].", "content": "The author made a series of observations in 17 cases of acute keratoconus. He performed perforating keratoplasties on 18 eyes of 16 patients promptly in the acute phases. The results were the same as after keratoplasty in cases of simple keratoconus. He informs of his observations regarding the probable causes of bringing about the acute phase.", "contents": "[Therapy of acute keratoconus]. The author made a series of observations in 17 cases of acute keratoconus. He performed perforating keratoplasties on 18 eyes of 16 patients promptly in the acute phases. The results were the same as after keratoplasty in cases of simple keratoconus. He informs of his observations regarding the probable causes of bringing about the acute phase."} {"id": "PMID:158105", "title": "[The histological substrate of the extraocular muscle thickening seen in dysthyroid orbitopathy (author's transl)].", "content": "The diagnosis of dysthyroid orbitopathy can be confirmed in over 80% of cases by demonstrating thickened extraocular muscles on computertomograms. The criteria are briefly discussed and the histological picture of the muscle thickening is described. The changes are variable and depend upon the course of the disease. Fatty infiltration is the most important factor causing muscle thickening, mucopolysaccharide deposition and fibrosis contribute less to the increased muscle volume, while inflammatory cell infiltration and proliferation of the endomysium play a minor role. The fatty infiltration and fibrosis, representing late changes, are probably therapy resistant in contrast to the other changes.", "contents": "[The histological substrate of the extraocular muscle thickening seen in dysthyroid orbitopathy (author's transl)]. The diagnosis of dysthyroid orbitopathy can be confirmed in over 80% of cases by demonstrating thickened extraocular muscles on computertomograms. The criteria are briefly discussed and the histological picture of the muscle thickening is described. The changes are variable and depend upon the course of the disease. Fatty infiltration is the most important factor causing muscle thickening, mucopolysaccharide deposition and fibrosis contribute less to the increased muscle volume, while inflammatory cell infiltration and proliferation of the endomysium play a minor role. The fatty infiltration and fibrosis, representing late changes, are probably therapy resistant in contrast to the other changes."} {"id": "PMID:158106", "title": "[Decreased serum protein binding of glymidine in icteric liver disease and its partial correction with charcoal (author's transl].", "content": "In patients with hyperbilirubinemic liver disease serum protein binding of the antidiabetic agent glymidine is reduced considerably. After treatment of the serum with charcoal the reduced glymidine binding can be assimilated partly, but not completely, to the glymidine binding in healthy subjects. It may be concluded there from that the reduced glymidine binding in patients with hyperbilirubinemic liver disease has to be partly caused by substances which are retained in the blood of these patients. Besides bilirubin, other substances must be responsible herefore. Bilirubin, when added in vitro to the serum of healthy subjects, is not able to decrease glymidine binding to a degree similar to the results obtained in the patients with liver disease.", "contents": "[Decreased serum protein binding of glymidine in icteric liver disease and its partial correction with charcoal (author's transl]. In patients with hyperbilirubinemic liver disease serum protein binding of the antidiabetic agent glymidine is reduced considerably. After treatment of the serum with charcoal the reduced glymidine binding can be assimilated partly, but not completely, to the glymidine binding in healthy subjects. It may be concluded there from that the reduced glymidine binding in patients with hyperbilirubinemic liver disease has to be partly caused by substances which are retained in the blood of these patients. Besides bilirubin, other substances must be responsible herefore. Bilirubin, when added in vitro to the serum of healthy subjects, is not able to decrease glymidine binding to a degree similar to the results obtained in the patients with liver disease."} {"id": "PMID:158107", "title": "Eradication of the pinworm Syphacia obvelata from an animal unit by anthelmintic therapy.", "content": "Thiabendazole incorporated in the diet at a rate of 0.1%, fed to all animals over a period of 3 months, successfully eliminated the parasite from the colony. Samples taken 12 months after treatment were still negative for the parasite. During the period between the discovery of the organism and the preparation of the diet a course of piperazine citrate was administered at a rate of 2 g/litre in the drinking water in order to limit the spread of the infection.", "contents": "Eradication of the pinworm Syphacia obvelata from an animal unit by anthelmintic therapy. Thiabendazole incorporated in the diet at a rate of 0.1%, fed to all animals over a period of 3 months, successfully eliminated the parasite from the colony. Samples taken 12 months after treatment were still negative for the parasite. During the period between the discovery of the organism and the preparation of the diet a course of piperazine citrate was administered at a rate of 2 g/litre in the drinking water in order to limit the spread of the infection."} {"id": "PMID:158111", "title": "[Therapy of rhinophyma on the tip and sides of the nose].", "content": "The commonly used methods of removing a Rhinophyma are described. An own modificated decortations-excisions-technique in the area of the tip of the nose and the wings of the nose will be demonstrated.", "contents": "[Therapy of rhinophyma on the tip and sides of the nose]. The commonly used methods of removing a Rhinophyma are described. An own modificated decortations-excisions-technique in the area of the tip of the nose and the wings of the nose will be demonstrated."} {"id": "PMID:158112", "title": "Maintenance of cochlear function with artificial oxygen carriers.", "content": "By means of vascular perfusion via the anterior inferior cerebellar artery with a blood substitute containing the perfluorochemical FC 47 as oxygen carrier, it is possible to maintain normal or near normal levels of the cochlear microphonics and the endolymphatic potential of the guinea pig for perios of 90 min, or longer. Following 60 min. of perfusion with artificial blood, the levels of ATP and 5' AMP in the stria vascularis and the organ of Corti are comparable to those of nonperfused control animals maintained at optimal metabolic conditions. Following the same period of perfusion, the appearance of the organ of Corti is normal, but small vacuoles, presumably deposits of FC 47, are visible in the marginal cells of the stria vascularis. Preliminary experiments concerning the survival time and the revival time of the cochlear potentials, as well as the response to furosemide, ouabain, and mersalyl are presented to illustrate the value of this method in elucidating various biochemical and pharmacological problems of the cochlea.", "contents": "Maintenance of cochlear function with artificial oxygen carriers. By means of vascular perfusion via the anterior inferior cerebellar artery with a blood substitute containing the perfluorochemical FC 47 as oxygen carrier, it is possible to maintain normal or near normal levels of the cochlear microphonics and the endolymphatic potential of the guinea pig for perios of 90 min, or longer. Following 60 min. of perfusion with artificial blood, the levels of ATP and 5' AMP in the stria vascularis and the organ of Corti are comparable to those of nonperfused control animals maintained at optimal metabolic conditions. Following the same period of perfusion, the appearance of the organ of Corti is normal, but small vacuoles, presumably deposits of FC 47, are visible in the marginal cells of the stria vascularis. Preliminary experiments concerning the survival time and the revival time of the cochlear potentials, as well as the response to furosemide, ouabain, and mersalyl are presented to illustrate the value of this method in elucidating various biochemical and pharmacological problems of the cochlea."} {"id": "PMID:158119", "title": "Leg extension power and muscle fiber composition.", "content": "The purpose of this investigation was to relate muscle fiber composition to the isokinetic measure of peak torque production through a range of leg extension velocities. Twenty-one males were biopsied from the vastus lateralis muscle to determine their percent distribution of slow twitch (%ST) and fast twitch (%FT) muscle fibers as identified through myofibrillar adenosine triphosphatase activity. All subjects showed a decline in peak torque with increasing velocities. Subjects with predominantly FT fibers were able to generate 11, 16, 23 and 47 percent greater relative peak torque than could predominantly ST subjects at lever arm velocities of 115, 200, 287 and 400 degrees/second respectively. Likewise the correlation between relative torque production and % FT were significant (p less than .05) and increased from r = 0.44 to r = 0.75 as velocity increased from 115 to 400 degrees/second respectively. These data suggest that muscle fiber composition becomes increasingly more related to power performance as the velocity of movement increases.", "contents": "Leg extension power and muscle fiber composition. The purpose of this investigation was to relate muscle fiber composition to the isokinetic measure of peak torque production through a range of leg extension velocities. Twenty-one males were biopsied from the vastus lateralis muscle to determine their percent distribution of slow twitch (%ST) and fast twitch (%FT) muscle fibers as identified through myofibrillar adenosine triphosphatase activity. All subjects showed a decline in peak torque with increasing velocities. Subjects with predominantly FT fibers were able to generate 11, 16, 23 and 47 percent greater relative peak torque than could predominantly ST subjects at lever arm velocities of 115, 200, 287 and 400 degrees/second respectively. Likewise the correlation between relative torque production and % FT were significant (p less than .05) and increased from r = 0.44 to r = 0.75 as velocity increased from 115 to 400 degrees/second respectively. These data suggest that muscle fiber composition becomes increasingly more related to power performance as the velocity of movement increases."} {"id": "PMID:158122", "title": "A study of the organisation of the ribosomal ribonucleic acid gene cluster of Neurospora crassa by means of restriction endonuclease analysis and cloning in bacteriophage lambda.", "content": "1. Total Neurospora crassa DNA was restricted with endonucleases and fragments carrying rRNA coding sequences were identified by hybridization with Xenopus laevis ribosomal DNA probes. 2. The repeating unit of the rRNA gene cluster was found to be 8.6 kbp, arranged in a head-to-tail fashion. 3. Digestion with Hind III yielded fragments of 3.4 kbp and 5.2 kbp and both were cloned. 4. Digestion with Eco RI yielded fragments of 2.2 kbp, 3.0 kbp and 3.4 kbp; the 3.0 kbp fragment was cloned. 5. Sequences coding for RNA (S-rRNA)1 of the smaller subribosomal particle were found (at least 90%) in the 2.2 kbp EcoRI subfragment of the 5.2 kbp Hind III fragment. 6. The coding sequences for the major RNA species (L-rRNA) of the larger subribosomal particle were located mainly (at least 95%) in the 3.4 kbp Hind III fragment. 7. For comparison, a Hind III digest of total yeast DNA was cloned and recombinants containing a 6.4 kbp rDNA fragment were isolated.", "contents": "A study of the organisation of the ribosomal ribonucleic acid gene cluster of Neurospora crassa by means of restriction endonuclease analysis and cloning in bacteriophage lambda. 1. Total Neurospora crassa DNA was restricted with endonucleases and fragments carrying rRNA coding sequences were identified by hybridization with Xenopus laevis ribosomal DNA probes. 2. The repeating unit of the rRNA gene cluster was found to be 8.6 kbp, arranged in a head-to-tail fashion. 3. Digestion with Hind III yielded fragments of 3.4 kbp and 5.2 kbp and both were cloned. 4. Digestion with Eco RI yielded fragments of 2.2 kbp, 3.0 kbp and 3.4 kbp; the 3.0 kbp fragment was cloned. 5. Sequences coding for RNA (S-rRNA)1 of the smaller subribosomal particle were found (at least 90%) in the 2.2 kbp EcoRI subfragment of the 5.2 kbp Hind III fragment. 6. The coding sequences for the major RNA species (L-rRNA) of the larger subribosomal particle were located mainly (at least 95%) in the 3.4 kbp Hind III fragment. 7. For comparison, a Hind III digest of total yeast DNA was cloned and recombinants containing a 6.4 kbp rDNA fragment were isolated."} {"id": "PMID:158124", "title": "In vitro immune response of human peripheral lymphocytes. II. Properties and functions of concanavalin A-induced suppressor T cells.", "content": "Con A-stimulation of human peripheral T lymphocytes induced both suppressor and helper T cells. ConA-generated suppressor T cells inhibited PWM-induced IgG and IgM production in PBL. Lower concentrations of Con A (0.5 micrograms/ml) or shorter incubation periods (6 to 24 hr) induced mainly helper T cells, while higher concentrations of Con A (10 micrograms/ml) or longer incubation periods (at least 48 hr) induced suppressor T cells. Con A-generated suppressor T cells were sensitive to mitomycin treatment and exerted their suppressor function on the early phase of differentiation and/or proliferation of B cells but not on the final differentiation of B cells to Ig-producing cells. The identity of the MHC was not required for the expression of suppressor function. Suppressor T cells competed with helper T cells in PWM-induced Ig-production of PBL. This experimental system can be applied to estimate the regulatory function of T cells in several disease states.", "contents": "In vitro immune response of human peripheral lymphocytes. II. Properties and functions of concanavalin A-induced suppressor T cells. Con A-stimulation of human peripheral T lymphocytes induced both suppressor and helper T cells. ConA-generated suppressor T cells inhibited PWM-induced IgG and IgM production in PBL. Lower concentrations of Con A (0.5 micrograms/ml) or shorter incubation periods (6 to 24 hr) induced mainly helper T cells, while higher concentrations of Con A (10 micrograms/ml) or longer incubation periods (at least 48 hr) induced suppressor T cells. Con A-generated suppressor T cells were sensitive to mitomycin treatment and exerted their suppressor function on the early phase of differentiation and/or proliferation of B cells but not on the final differentiation of B cells to Ig-producing cells. The identity of the MHC was not required for the expression of suppressor function. Suppressor T cells competed with helper T cells in PWM-induced Ig-production of PBL. This experimental system can be applied to estimate the regulatory function of T cells in several disease states."} {"id": "PMID:158126", "title": "[Determination of the glucose reserves in the water of the Rybinsk reservoir].", "content": "The concentrations of glucose (Km + Sn) was determined by the method of Parson and Strickland in the water of the Rybinsk and Sheksna Reservoirs. It varied from 11 to 31 mcg C per litre and reached 380 mcg C per litre in swamp waters. The rate of glucose assimilation by the microflora varied from 0.02 to 0.56 mcg C per litre per hour and reached 5--7 mcg C per litre per hour in contaminated waters.", "contents": "[Determination of the glucose reserves in the water of the Rybinsk reservoir]. The concentrations of glucose (Km + Sn) was determined by the method of Parson and Strickland in the water of the Rybinsk and Sheksna Reservoirs. It varied from 11 to 31 mcg C per litre and reached 380 mcg C per litre in swamp waters. The rate of glucose assimilation by the microflora varied from 0.02 to 0.56 mcg C per litre per hour and reached 5--7 mcg C per litre per hour in contaminated waters."} {"id": "PMID:158131", "title": "Histoarchitectonics of the fetal thymus. A three-dimensional model study.", "content": "Comparative studies on three-dimensional models give new possibilities in examination of the internal and external evolution of the thymus, phenomena that occur concomitantly with the histogenesis of the organ during the fetal life period. During the antenatal period, the invasion and burgeoning of capillaries represent a strong potential of biostimulation with a special role in organizing and determining thymus lobulation.", "contents": "Histoarchitectonics of the fetal thymus. A three-dimensional model study. Comparative studies on three-dimensional models give new possibilities in examination of the internal and external evolution of the thymus, phenomena that occur concomitantly with the histogenesis of the organ during the fetal life period. During the antenatal period, the invasion and burgeoning of capillaries represent a strong potential of biostimulation with a special role in organizing and determining thymus lobulation."} {"id": "PMID:158133", "title": "Trichinous nephropathy.", "content": "Lesions of glomerular nephropathy were found in 5 cases of acute trichinosis, characterized by a low proteinuria and hematuria as well as by moderate deficit of the renal function. Renal biopsy revealed lesions of proliferative glomerulitis, while immunofluorescence examination showed granular deposits of IgG and beta1-C-globulin on basement membranes. Serum complement was reduced. These observations suggest an immunological mechanism in the development of the glomerular nephropathy during acute trichinosis.", "contents": "Trichinous nephropathy. Lesions of glomerular nephropathy were found in 5 cases of acute trichinosis, characterized by a low proteinuria and hematuria as well as by moderate deficit of the renal function. Renal biopsy revealed lesions of proliferative glomerulitis, while immunofluorescence examination showed granular deposits of IgG and beta1-C-globulin on basement membranes. Serum complement was reduced. These observations suggest an immunological mechanism in the development of the glomerular nephropathy during acute trichinosis."} {"id": "PMID:158134", "title": "Histochemical study of leucine aminopeptidase in leukemia.", "content": "By means of a histochemical method, the leucine aminopeptidase activity was studied in human normal and leukemic peripheral blood. Before administration of cytostatics the enzymic activity was high in the cytoplasm of blasts and in the nuclei of segmented cells. After therapy the activity of leucine aminopeptidase in blasts decreased, while in polymorphs it became negative in nuclei and positive in their cytoplasm. The non-granular leukocytes and platelets displayed a weak enzymic activity both in normal and malignant blood cells. The erythrocytes were negative.", "contents": "Histochemical study of leucine aminopeptidase in leukemia. By means of a histochemical method, the leucine aminopeptidase activity was studied in human normal and leukemic peripheral blood. Before administration of cytostatics the enzymic activity was high in the cytoplasm of blasts and in the nuclei of segmented cells. After therapy the activity of leucine aminopeptidase in blasts decreased, while in polymorphs it became negative in nuclei and positive in their cytoplasm. The non-granular leukocytes and platelets displayed a weak enzymic activity both in normal and malignant blood cells. The erythrocytes were negative."} {"id": "PMID:158132", "title": "[Vital fluorochroming showing the effect of cyclophosphamide on the embryo].", "content": "Besides the usual methods, vital fluorochroming may globally show the extent of the cytotoxic effect of Cyclophosphamide (CP). By intravital treatment with highly diluted fluorochromes (acridine-orange, etc.) necrobiotic and dead cells, cell debris and phagosomes appear electively fluorescent. Glycosaminoglycans and various mucopolysaccharides show a somewhat weaker fluorescence. Autopods and the mesencephalon were selected for comparative assessment of the effect of other cytotoxic agents. Important results were also obtained by the repeated examination of blood (erythrocytes) and of hemopoetic foci. Cytotoxic effect within the embryo, teratogenesis and chemotherapeutic action are strongly correlated.", "contents": "[Vital fluorochroming showing the effect of cyclophosphamide on the embryo]. Besides the usual methods, vital fluorochroming may globally show the extent of the cytotoxic effect of Cyclophosphamide (CP). By intravital treatment with highly diluted fluorochromes (acridine-orange, etc.) necrobiotic and dead cells, cell debris and phagosomes appear electively fluorescent. Glycosaminoglycans and various mucopolysaccharides show a somewhat weaker fluorescence. Autopods and the mesencephalon were selected for comparative assessment of the effect of other cytotoxic agents. Important results were also obtained by the repeated examination of blood (erythrocytes) and of hemopoetic foci. Cytotoxic effect within the embryo, teratogenesis and chemotherapeutic action are strongly correlated."} {"id": "PMID:158136", "title": "Spleen and lymph node changes in rats irradiated with X-rays and treated with testosterone.", "content": "The authors have studied the effect of testosterone administration in male adult Wistar rats irradiated with a single total dose of 800 r X-rays. The results obtained show that testosterone exerts a double radioprotective action. This hormone prevents both the occurrence of the senile type spleen and lymph node changes and the depression of the colloidopexic capacity of the hepatosplenic macrophages. At the same time, these results suggest that testosterone induces hyperplasia of the lymphocytic elements, particularly of T lymphocytes.", "contents": "Spleen and lymph node changes in rats irradiated with X-rays and treated with testosterone. The authors have studied the effect of testosterone administration in male adult Wistar rats irradiated with a single total dose of 800 r X-rays. The results obtained show that testosterone exerts a double radioprotective action. This hormone prevents both the occurrence of the senile type spleen and lymph node changes and the depression of the colloidopexic capacity of the hepatosplenic macrophages. At the same time, these results suggest that testosterone induces hyperplasia of the lymphocytic elements, particularly of T lymphocytes."} {"id": "PMID:158137", "title": "Behaviour of mucopolysaccharides of Kupffer cells in experimental mercury hepatitis.", "content": "A reaction of Kupffer cells with changes of mucopolysaccharides is shown during experimental mercury hepatitis. An initial diminution of the reaction intensity is followed by the increase of MPS polymerization degree. Association of effort leads to a significant increase of the A-PAS reaction. The lympho-histiocytes infiltrating portal spaces present the same MPS dynamics.", "contents": "Behaviour of mucopolysaccharides of Kupffer cells in experimental mercury hepatitis. A reaction of Kupffer cells with changes of mucopolysaccharides is shown during experimental mercury hepatitis. An initial diminution of the reaction intensity is followed by the increase of MPS polymerization degree. Association of effort leads to a significant increase of the A-PAS reaction. The lympho-histiocytes infiltrating portal spaces present the same MPS dynamics."} {"id": "PMID:158135", "title": "Pulmonary blastoma.", "content": "A case of pulmonary blastoma in a 8-year-old girl is reported. The histopathologic analysis evidenced carcinomatous tubes with several cell layers developing into a mesenchymal cell mass with undifferentiated elements forming a dendroreticulated network with minimal endothelial, fibroblastic and collagenous differentiations. The initial tumoral formation within the lower left lobe was rapidly followed after resection by a local recidive and nine months later by a voluminous metastatic formation within the upper left lobe, radiologically treated. Discussion of the histopathologic characteristics of this case supports the hypothesis of a peculiar neoplastic entity of the lung, in which only the epithelial component of the lung was involved, while the mesenchymal mass presented an unaffected fetal structure.", "contents": "Pulmonary blastoma. A case of pulmonary blastoma in a 8-year-old girl is reported. The histopathologic analysis evidenced carcinomatous tubes with several cell layers developing into a mesenchymal cell mass with undifferentiated elements forming a dendroreticulated network with minimal endothelial, fibroblastic and collagenous differentiations. The initial tumoral formation within the lower left lobe was rapidly followed after resection by a local recidive and nine months later by a voluminous metastatic formation within the upper left lobe, radiologically treated. Discussion of the histopathologic characteristics of this case supports the hypothesis of a peculiar neoplastic entity of the lung, in which only the epithelial component of the lung was involved, while the mesenchymal mass presented an unaffected fetal structure."} {"id": "PMID:158138", "title": "Infection in vitro of the human pulmonary macrophage with Staphylococcus aureus (bacteriologic and ultrastructural observations).", "content": "Alveolar macrophages from exeresis fragments taken from patients operated for pulmonary cancer were infected in vitro with Staphylococcus aureus. Part of the investigation was carried out in the presence of an antibiotic (pyopen) introduced in the culture medium. Bacteriologic seeding from an extracellular medium and from lyzed cells showed a greater intracellular multiplication rate. In the presence of pyopen there was a decrease in the number of germs due to the inhibition of multiplication. Electron microscopy revealed reduced phagolysosomal fusion, aspects of bacterial multiplication and the coexistence of intact bacteria and bacteria presenting structural alterations. The results suggest the importance of cellular parasitism in the chronic evolution of infectious bronchopulmonary processes.", "contents": "Infection in vitro of the human pulmonary macrophage with Staphylococcus aureus (bacteriologic and ultrastructural observations). Alveolar macrophages from exeresis fragments taken from patients operated for pulmonary cancer were infected in vitro with Staphylococcus aureus. Part of the investigation was carried out in the presence of an antibiotic (pyopen) introduced in the culture medium. Bacteriologic seeding from an extracellular medium and from lyzed cells showed a greater intracellular multiplication rate. In the presence of pyopen there was a decrease in the number of germs due to the inhibition of multiplication. Electron microscopy revealed reduced phagolysosomal fusion, aspects of bacterial multiplication and the coexistence of intact bacteria and bacteria presenting structural alterations. The results suggest the importance of cellular parasitism in the chronic evolution of infectious bronchopulmonary processes."} {"id": "PMID:158141", "title": "Large-scale preparation of synaptosomes from bovine brain using a zonal rotor technique.", "content": "A zonal rotor technique for the preparation of synaptosomes in bulk from bovine brain frontal cortex based on an impirical transformation of a small-volume discontinuous sucrose density gradient arrangement is presented in detail. The procedure yields new information concerning synaptosomes prepared in sucrose gradients. Cerebroside analysis and electron microscopy show myelin contamination to be restricted to the leading, less dense edge of the synaptosomal profile, free mitochondria to the trailing, more dense edge. Exclusion of fringe areas yields a highly purified synaptosome preparation which entirely enters the next dense layer beyond the 0.8 : 1.2 M sucrose interface. This interface collects most of the oubain-sensitive (Na+, K+) adenosine triphosphatase activity. The purified synaptosomes display very high intrinsic sialidase activity and are rich in di-, tri-, and tetrasialogangliosides, the preferred substrates for the enzyme. Up to 90% of the cholinesterase activity in the zonal rotor synaptosome preparation is specific acetylcholinesterase.", "contents": "Large-scale preparation of synaptosomes from bovine brain using a zonal rotor technique. A zonal rotor technique for the preparation of synaptosomes in bulk from bovine brain frontal cortex based on an impirical transformation of a small-volume discontinuous sucrose density gradient arrangement is presented in detail. The procedure yields new information concerning synaptosomes prepared in sucrose gradients. Cerebroside analysis and electron microscopy show myelin contamination to be restricted to the leading, less dense edge of the synaptosomal profile, free mitochondria to the trailing, more dense edge. Exclusion of fringe areas yields a highly purified synaptosome preparation which entirely enters the next dense layer beyond the 0.8 : 1.2 M sucrose interface. This interface collects most of the oubain-sensitive (Na+, K+) adenosine triphosphatase activity. The purified synaptosomes display very high intrinsic sialidase activity and are rich in di-, tri-, and tetrasialogangliosides, the preferred substrates for the enzyme. Up to 90% of the cholinesterase activity in the zonal rotor synaptosome preparation is specific acetylcholinesterase."} {"id": "PMID:158142", "title": "[Evaluation of the results of treatment of low backache by acupuncture or suggesting (preliminary report)].", "content": "In a group of 34 patients with lumbosacral pain acupuncture was applied in 18 cases and suggestion in 16 cases and the results of both methods were compared. The therapeutic effects were evaluated immediately after the procedure and after a series of 4 procedures. The therapeutic results were better both immediately and after a series of acupuncture. The difference in the results of treatment was statistically significant in the patients with longest duration of pains. Presence of degenerative spinal changes was without influence on the results of treatment by both methods.", "contents": "[Evaluation of the results of treatment of low backache by acupuncture or suggesting (preliminary report)]. In a group of 34 patients with lumbosacral pain acupuncture was applied in 18 cases and suggestion in 16 cases and the results of both methods were compared. The therapeutic effects were evaluated immediately after the procedure and after a series of 4 procedures. The therapeutic results were better both immediately and after a series of acupuncture. The difference in the results of treatment was statistically significant in the patients with longest duration of pains. Presence of degenerative spinal changes was without influence on the results of treatment by both methods."} {"id": "PMID:158166", "title": "Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome.", "content": "Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia.", "contents": "Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome. Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia."} {"id": "PMID:158161", "title": "Rhinophyma in tuberous sclerosis.", "content": "Search of the literature thus far indicates no prior description of rhinophyma occuring in tuberous sclerosis. There have been numerous reports of the usual skin lesion, adenoma sebaceum, together with the associated manifestations of severe mental retardation and convulsive seizures. In a 27-year-old woman, full-blown, severely deforming rhinophyma had its onset one year prior to her hospital admission. The family, horrified by her appearance, desired surgical intervention. The report includes a review of the literature and a description of the patient and of the surgical technique employed. The question of the desirability and difficulty involved in skin grafting is discussed, as are the microscopic findings and postoperative course. Particular attention is directed toward differential diagnosis and associated findings.", "contents": "Rhinophyma in tuberous sclerosis. Search of the literature thus far indicates no prior description of rhinophyma occuring in tuberous sclerosis. There have been numerous reports of the usual skin lesion, adenoma sebaceum, together with the associated manifestations of severe mental retardation and convulsive seizures. In a 27-year-old woman, full-blown, severely deforming rhinophyma had its onset one year prior to her hospital admission. The family, horrified by her appearance, desired surgical intervention. The report includes a review of the literature and a description of the patient and of the surgical technique employed. The question of the desirability and difficulty involved in skin grafting is discussed, as are the microscopic findings and postoperative course. Particular attention is directed toward differential diagnosis and associated findings."} {"id": "PMID:158162", "title": "[Blood digestion and the formation of a plague block in Ceratophyllus tesquorum fleas].", "content": "The fleas of C. tesquorum are characterized by high protease activity in the epithelium and contents of the stomach, quick hemolysis of erythrocytes and low blood coagulation. Rare blockformation in C. tesquorum and its long terms under experimental conditions are apparently associated with changes in the quantity of plague microbes in the digestive tract depending on the stage of blood digestion: reduced during the hemolysis of erythrocytes and increased when it was over.", "contents": "[Blood digestion and the formation of a plague block in Ceratophyllus tesquorum fleas]. The fleas of C. tesquorum are characterized by high protease activity in the epithelium and contents of the stomach, quick hemolysis of erythrocytes and low blood coagulation. Rare blockformation in C. tesquorum and its long terms under experimental conditions are apparently associated with changes in the quantity of plague microbes in the digestive tract depending on the stage of blood digestion: reduced during the hemolysis of erythrocytes and increased when it was over."} {"id": "PMID:158164", "title": "[Myxobolus tauricus sp. n., a new species of myxosporidians (Cnidosporidia: Myxosporidia) from the Crimean barbel].", "content": "While studying the parasite fauna of freshwater fishes of the Crimea (1971 to 1977) a new species of myxosporidians, Myxobolus tauricus sp. n., from Barbus tauricus (Kessler, 1887) was erected. A description, figure and differential diagnosis are given. The location sites are indicated as follows: the rivers Salgir, Alma, Bijuk-Karasu, Chernaja, Uchan-Su (the Crimea, USSR). The places of localization are indicated too: gills, fins, liver, kidneys, urinary bladder, brain, spiral cord, muscles.", "contents": "[Myxobolus tauricus sp. n., a new species of myxosporidians (Cnidosporidia: Myxosporidia) from the Crimean barbel]. While studying the parasite fauna of freshwater fishes of the Crimea (1971 to 1977) a new species of myxosporidians, Myxobolus tauricus sp. n., from Barbus tauricus (Kessler, 1887) was erected. A description, figure and differential diagnosis are given. The location sites are indicated as follows: the rivers Salgir, Alma, Bijuk-Karasu, Chernaja, Uchan-Su (the Crimea, USSR). The places of localization are indicated too: gills, fins, liver, kidneys, urinary bladder, brain, spiral cord, muscles."} {"id": "PMID:158163", "title": "[Flagellata isolated from sandflies in various zones of Turkmenia and their related cultures of the causative agents of leishmaniasis and the Leishmania of reptiles].", "content": "188 strains of Flagella from 6 species of sand flies and 42 strains from reptiles were isolated in various landscape-geographic zones of Turkmenia. 70 and 35 strains of Flagellata isolate from sand flies were studied by means of bio-assay on white mice and by the Adler's serological method (modification of Safjanova), respectively. 64 strains of Flagellata of different origin were studied by means of \"temperature\" method. It has been established that the transmission of the agent of zoonotic cutaneous leishmaniosis takes place nearly throughout the whole territory of Turkmenia. To identify an unknown strain of Leishmania by means of the Adler's method an antiserum for any studied \"standard\" strain of different species of Leishmania is enough to be used.", "contents": "[Flagellata isolated from sandflies in various zones of Turkmenia and their related cultures of the causative agents of leishmaniasis and the Leishmania of reptiles]. 188 strains of Flagella from 6 species of sand flies and 42 strains from reptiles were isolated in various landscape-geographic zones of Turkmenia. 70 and 35 strains of Flagellata isolate from sand flies were studied by means of bio-assay on white mice and by the Adler's serological method (modification of Safjanova), respectively. 64 strains of Flagellata of different origin were studied by means of \"temperature\" method. It has been established that the transmission of the agent of zoonotic cutaneous leishmaniosis takes place nearly throughout the whole territory of Turkmenia. To identify an unknown strain of Leishmania by means of the Adler's method an antiserum for any studied \"standard\" strain of different species of Leishmania is enough to be used."} {"id": "PMID:158170", "title": "Changes in the capillarity of skeletal muscle in the growing rat.", "content": "Capillary density (CD), capillary to fiber ratio (C/F), fiber cross sectional area (FCSA) and fiber composition were measured in the soleus and the gastrocnemius (medial head) muscles of rats weighing between 99 and 666 g. Muscle samples obtained from the anesthetized animal were rapidly frozen (-130 degrees C) sliced transversely at 16--18 micrometers, and treated histochemically by the ATPase method after preincubation at pH's of 4.0 and 4.4 to visualize capillaries and typify fibers. In both muscles the FCSA was positively related to body weight (BW) and muscle weight. At a given BW, the FCSA of the soleus was greater than that of the gastrocnemius. In both muscles CD decreased hyperbolically with FCSA (soleus: CD = 1.0613 X 10(6)/FCSA + 298.71; gastrocnemium: CD = 1.0349 X 10(6)/FCSA + 240.74). At the same time a positive linear correlation between C/F and FCSA was found (soleus: C/F = 3.92 X 10(-4) FCSA + 0.82; gastrocnemius: C/F = 2.90 X 10(-4) FCSA + 0.93). At a given FCSA, CD and C/F were greater in the soleus than in the gastrocnemius because of differences in fiber composition between the two muscles. The soleus had only oxidative fibers (STO and FTOG) whereas the gastrocnemius had 54% glycolytic fibers (FTG). The very large variability in CD and C/F values reported in the literature could, in part, be due to the differences in capillarity observed with maturation. A change in fiber composition with BW was observed in the soleus, but no systematic change occurred in the gastrocnemius.", "contents": "Changes in the capillarity of skeletal muscle in the growing rat. Capillary density (CD), capillary to fiber ratio (C/F), fiber cross sectional area (FCSA) and fiber composition were measured in the soleus and the gastrocnemius (medial head) muscles of rats weighing between 99 and 666 g. Muscle samples obtained from the anesthetized animal were rapidly frozen (-130 degrees C) sliced transversely at 16--18 micrometers, and treated histochemically by the ATPase method after preincubation at pH's of 4.0 and 4.4 to visualize capillaries and typify fibers. In both muscles the FCSA was positively related to body weight (BW) and muscle weight. At a given BW, the FCSA of the soleus was greater than that of the gastrocnemius. In both muscles CD decreased hyperbolically with FCSA (soleus: CD = 1.0613 X 10(6)/FCSA + 298.71; gastrocnemium: CD = 1.0349 X 10(6)/FCSA + 240.74). At the same time a positive linear correlation between C/F and FCSA was found (soleus: C/F = 3.92 X 10(-4) FCSA + 0.82; gastrocnemius: C/F = 2.90 X 10(-4) FCSA + 0.93). At a given FCSA, CD and C/F were greater in the soleus than in the gastrocnemius because of differences in fiber composition between the two muscles. The soleus had only oxidative fibers (STO and FTOG) whereas the gastrocnemius had 54% glycolytic fibers (FTG). The very large variability in CD and C/F values reported in the literature could, in part, be due to the differences in capillarity observed with maturation. A change in fiber composition with BW was observed in the soleus, but no systematic change occurred in the gastrocnemius."} {"id": "PMID:158184", "title": "Management of hypercalcemia.", "content": "Hypercalcemia calls first for supportive measures, eg, adequate hydration, movement or mobilization of the patient to the greatest amount tolerated, and reevaluation of drugs being taken. When immediate lowering of the serum calcium level is not clinically mandatory, oral administration of furosemide, corticosteroid, or phosphorus should be considered. In acute emergencies, saline loading and parenteral furosemide therapy should be tried first, except in a patient with renal failure and congestive heart failure, in whom peritoneal dialysis or hemodialysis should be used instead. Calcitonin can be given for the first 12 to 24 hours to lower serum calcium concentration until a definitive management plan is formulated. Corticosteroid, if not contraindicated, should be started as soon as possible. In severe primary hyperparathyroidism with hypophosphatemia, phosphorus can be given intravenously until oral phosphate therapy can be established. Surgery, of course, should be performed as soon as possible. In most cases of neoplasia, mithramycin given according to a recommended schedule is safe and frequently effective. In desperate cases, additional use of prostaglandin synthesis inhibitors probably now is justified by empirical observations. All of these therapeutic measures are used only to stabilize electrolyte balance so that the primary cause of the hypercalcemia can be treated.", "contents": "Management of hypercalcemia. Hypercalcemia calls first for supportive measures, eg, adequate hydration, movement or mobilization of the patient to the greatest amount tolerated, and reevaluation of drugs being taken. When immediate lowering of the serum calcium level is not clinically mandatory, oral administration of furosemide, corticosteroid, or phosphorus should be considered. In acute emergencies, saline loading and parenteral furosemide therapy should be tried first, except in a patient with renal failure and congestive heart failure, in whom peritoneal dialysis or hemodialysis should be used instead. Calcitonin can be given for the first 12 to 24 hours to lower serum calcium concentration until a definitive management plan is formulated. Corticosteroid, if not contraindicated, should be started as soon as possible. In severe primary hyperparathyroidism with hypophosphatemia, phosphorus can be given intravenously until oral phosphate therapy can be established. Surgery, of course, should be performed as soon as possible. In most cases of neoplasia, mithramycin given according to a recommended schedule is safe and frequently effective. In desperate cases, additional use of prostaglandin synthesis inhibitors probably now is justified by empirical observations. All of these therapeutic measures are used only to stabilize electrolyte balance so that the primary cause of the hypercalcemia can be treated."} {"id": "PMID:158193", "title": "Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin levels.", "content": "The methylester hydrochlorides of DL-p-chlorophenylalanine (PCPA), L-leucine and L-tryptophan were intraventricularly administered to rats. All compounds produced increased food intake compared to saline administration. PCPA and leucine administration significantly decreased serotonin levels by 15--18%, while no serotonin depletion occurred following tryptophan injections. The data suggest that intraventricular injections of large quantities of neutral amino acid methyl esters may cause hyperphagia in rats through non-serotonergic effects on brain function.", "contents": "Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin levels. The methylester hydrochlorides of DL-p-chlorophenylalanine (PCPA), L-leucine and L-tryptophan were intraventricularly administered to rats. All compounds produced increased food intake compared to saline administration. PCPA and leucine administration significantly decreased serotonin levels by 15--18%, while no serotonin depletion occurred following tryptophan injections. The data suggest that intraventricular injections of large quantities of neutral amino acid methyl esters may cause hyperphagia in rats through non-serotonergic effects on brain function."} {"id": "PMID:158196", "title": "Masked depressions in obstetrics and gynecology.", "content": "The development of psychosomatic symptoms should not be viewed exclusively under the aspect of anxiety or defense against anxiety. In another study, we have shown that affects other than anxiety can lead to functional obstetric disturbances (2). The insight that depressions, above all masked depressions can be the basis of many psychosomatic symptoms in obstetrics and gynecology paves the way for good therapeutic possibilities in many cases that have been resistant to therapy heretofore. Antidepressants often bring prompt relief from symptoms. Psychotherapy is possible in numerous cases following success in prescribing antidepressants.", "contents": "Masked depressions in obstetrics and gynecology. The development of psychosomatic symptoms should not be viewed exclusively under the aspect of anxiety or defense against anxiety. In another study, we have shown that affects other than anxiety can lead to functional obstetric disturbances (2). The insight that depressions, above all masked depressions can be the basis of many psychosomatic symptoms in obstetrics and gynecology paves the way for good therapeutic possibilities in many cases that have been resistant to therapy heretofore. Antidepressants often bring prompt relief from symptoms. Psychotherapy is possible in numerous cases following success in prescribing antidepressants."} {"id": "PMID:158199", "title": "[The radiographic diagnosis of posterior dislocation of the shoulder (author's transl)].", "content": "In spite of its clinical features, the diagnosis of posterior dislocation of the shoulder is often missed. The authors considered that this is due to an inadequate analysis of the x-rays. They show that the diagnosis can be made on an antero-posterior x-ray and describe the findings in fourteen cases. They note a modification of the gleno-humera line and the features of the associated impaction fracture. A lateral view is necessary to make the diagnosis certain, an axillary view being preferred to a trans-thoracic late-femoral head or of the posterior glenoid margin.", "contents": "[The radiographic diagnosis of posterior dislocation of the shoulder (author's transl)]. In spite of its clinical features, the diagnosis of posterior dislocation of the shoulder is often missed. The authors considered that this is due to an inadequate analysis of the x-rays. They show that the diagnosis can be made on an antero-posterior x-ray and describe the findings in fourteen cases. They note a modification of the gleno-humera line and the features of the associated impaction fracture. A lateral view is necessary to make the diagnosis certain, an axillary view being preferred to a trans-thoracic late-femoral head or of the posterior glenoid margin."} {"id": "PMID:158201", "title": "[Elimination of partial premature epiphyseal closure by transplantation of epiphyseal cartilage. An experimental study (author's transl)].", "content": "An experimental study was made on 118 rabbits aimed at restoring bone growth after partial epiphyseal closure. In a first stage, a partial epiphyseal closure was made at the level of the lower femoral growth plate by excision of the growth cartilage and insertion of a bone graft. In a second stage, the bony bridge was removed and a segment of iliac crest growth cartilage was transplanted. It was concluded, on the basis of radiographic and histological studies that the best results were obtained when the growth cartilage was transplanted alone or with a thin layer of bone. The results were poor when the layer of bone transplanted with the cartilage was too thick.", "contents": "[Elimination of partial premature epiphyseal closure by transplantation of epiphyseal cartilage. An experimental study (author's transl)]. An experimental study was made on 118 rabbits aimed at restoring bone growth after partial epiphyseal closure. In a first stage, a partial epiphyseal closure was made at the level of the lower femoral growth plate by excision of the growth cartilage and insertion of a bone graft. In a second stage, the bony bridge was removed and a segment of iliac crest growth cartilage was transplanted. It was concluded, on the basis of radiographic and histological studies that the best results were obtained when the growth cartilage was transplanted alone or with a thin layer of bone. The results were poor when the layer of bone transplanted with the cartilage was too thick."} {"id": "PMID:158202", "title": "[Plantar release in the treatment of pes cavus in childhood. Technique and indications (author's transl)].", "content": "The authors have operated on forty instances of pes cavus in children. Ten were idiopathic, nine poliomyelitic, five hemiplegic and five as a sequel of club foot. Others cases were of various neurological cause. In all cases, the plantar fasciae and ligaments were released; the technique of this procedure is fully described. In a number of cases, soft tissue release was associated with an osteotomy of the first metatarsal, a transplant of the extensor hallucis longus to the neck of the first metatarsal, an osteotomy of the calcaneus or various muscle transplants depending on the etiology of the cavus deformity. The results are analysed as are the complications. They were satisfactory in 66 p. 100 of cases. It is concluded that plantar release procedures may either avoid arthrodesis or may lead to it later but with the foot in a more satisfactory condition.", "contents": "[Plantar release in the treatment of pes cavus in childhood. Technique and indications (author's transl)]. The authors have operated on forty instances of pes cavus in children. Ten were idiopathic, nine poliomyelitic, five hemiplegic and five as a sequel of club foot. Others cases were of various neurological cause. In all cases, the plantar fasciae and ligaments were released; the technique of this procedure is fully described. In a number of cases, soft tissue release was associated with an osteotomy of the first metatarsal, a transplant of the extensor hallucis longus to the neck of the first metatarsal, an osteotomy of the calcaneus or various muscle transplants depending on the etiology of the cavus deformity. The results are analysed as are the complications. They were satisfactory in 66 p. 100 of cases. It is concluded that plantar release procedures may either avoid arthrodesis or may lead to it later but with the foot in a more satisfactory condition."} {"id": "PMID:158203", "title": "[Fatigue fracture of the patella in cerebral palsy (author's transl)].", "content": "Amongst approximately 1 500 spastic children under treatment, the authors have seen three cases of fatigue fracture of the patella. One patient was spastic and two others were athetotic. The fatigue fractures can be explained by a flexed knee gait aggravated by a contracture of the hamstring tendons. No fracture was seen in patients treated by Egger's operation. It is concluded that this procedure both prevents and cures fatigue fracture of the patella.", "contents": "[Fatigue fracture of the patella in cerebral palsy (author's transl)]. Amongst approximately 1 500 spastic children under treatment, the authors have seen three cases of fatigue fracture of the patella. One patient was spastic and two others were athetotic. The fatigue fractures can be explained by a flexed knee gait aggravated by a contracture of the hamstring tendons. No fracture was seen in patients treated by Egger's operation. It is concluded that this procedure both prevents and cures fatigue fracture of the patella."} {"id": "PMID:158204", "title": "[The use of an articulated brace in the treatment of juvenile kyphosis (author's transl)].", "content": "The authors have attempted to assess the efficiency of an articulated brace in the treatment of juvenile kyphosis (Scheuermann's disease and idiopathic kyphosis). Two series of patients were compared. Patients in both series were treated in a first stage by a plaster cast and in a second stage by a bivalve brace in the first series and an articulated brace in the second series. The technique of treatment by a plaster cast and by the brace is fully described. It is concluded that control of the lumbar lordosis is of great importance. The results were better with an articulated brace. The indications for treatment are given depending on the age at the onset of treatment, the type of spine deformity and its severity. In some cases of severe dorsolumbar kyphosis, surgery may be indicated.", "contents": "[The use of an articulated brace in the treatment of juvenile kyphosis (author's transl)]. The authors have attempted to assess the efficiency of an articulated brace in the treatment of juvenile kyphosis (Scheuermann's disease and idiopathic kyphosis). Two series of patients were compared. Patients in both series were treated in a first stage by a plaster cast and in a second stage by a bivalve brace in the first series and an articulated brace in the second series. The technique of treatment by a plaster cast and by the brace is fully described. It is concluded that control of the lumbar lordosis is of great importance. The results were better with an articulated brace. The indications for treatment are given depending on the age at the onset of treatment, the type of spine deformity and its severity. In some cases of severe dorsolumbar kyphosis, surgery may be indicated."} {"id": "PMID:158207", "title": "Effect of uncouplers and inhibitors of oxidative phosphorylation on the reduced and oxidized forms of mitochondiral ATPase.", "content": "A series of uncouplers and inhibitors of oxidative phosphorylation have been studied with regard to their effect on the hydrolytic activity of the reduced and oxidized forms of isolated or membrane-bound mitochondrial ATPase. Uncouplers (2,4-dinitrophenol, dicoumarol), which are also activators of the hydrolytic activity of ATPase, were more potent activators on the oxidized form of the enzyme. Inhibitors of oxidative phosphorylation (oligomycin, azide and amytal) had a more potent inhibitory effect on the hydrolytic activity of ATPase in its reduced form. Purified F1-ATPase, oligomycin insensitive in the oxidized form of the enzyme, became sensitive to oligomycin in the reduced form. An interpretation of the results suggests the presence of a mechanism that unifies the action of these different compounds on the synthesis and hydrolysis of ATP catalyzed by mitochondrial ATPase.", "contents": "Effect of uncouplers and inhibitors of oxidative phosphorylation on the reduced and oxidized forms of mitochondiral ATPase. A series of uncouplers and inhibitors of oxidative phosphorylation have been studied with regard to their effect on the hydrolytic activity of the reduced and oxidized forms of isolated or membrane-bound mitochondrial ATPase. Uncouplers (2,4-dinitrophenol, dicoumarol), which are also activators of the hydrolytic activity of ATPase, were more potent activators on the oxidized form of the enzyme. Inhibitors of oxidative phosphorylation (oligomycin, azide and amytal) had a more potent inhibitory effect on the hydrolytic activity of ATPase in its reduced form. Purified F1-ATPase, oligomycin insensitive in the oxidized form of the enzyme, became sensitive to oligomycin in the reduced form. An interpretation of the results suggests the presence of a mechanism that unifies the action of these different compounds on the synthesis and hydrolysis of ATP catalyzed by mitochondrial ATPase."} {"id": "PMID:158208", "title": "[Current educational practices with multiply handicpped pupils -- a problematic approach in special education (author's transl)].", "content": "The curricula of schools for the physically handicapped have, as yet, been influenced too much by those of regular schools. Which is why at special schools, too, the primary focus of all educational and therapeutic measures is placed on a qualification of the pupils. Also those pupils who, as a result of the severity of their disability, will not be able to enter vocational training are instructed on the basis of curricula modelled for the non-disabled. The purpose of the following article is to introduce this problem complex which has been present for years but not yet received satisfactory solutions. It is hoped that the described experiences gained with the three groups of pupils will stimulate the discussion.", "contents": "[Current educational practices with multiply handicpped pupils -- a problematic approach in special education (author's transl)]. The curricula of schools for the physically handicapped have, as yet, been influenced too much by those of regular schools. Which is why at special schools, too, the primary focus of all educational and therapeutic measures is placed on a qualification of the pupils. Also those pupils who, as a result of the severity of their disability, will not be able to enter vocational training are instructed on the basis of curricula modelled for the non-disabled. The purpose of the following article is to introduce this problem complex which has been present for years but not yet received satisfactory solutions. It is hoped that the described experiences gained with the three groups of pupils will stimulate the discussion."} {"id": "PMID:158209", "title": "[Attitudes of gainfully employed persons towards the vocational and social integration of the physically disabled (author's transl)].", "content": "Within the framework of a representative survey 1879 gainfully employed persons - trainees, workers, employees and supervisors - were asked about their attitudes towards the vocational and social integration of the physically disabled. The article describes the following results: 1) The majority of those who responded, particularly workers in subordinate positions, were of the opinion that firms, management and co-workers were rather unwilling to accept the physically disabled as competitive and equal employees and colleagues. 2) With regard to their personal attitudes there was a striking contrast: a high general support of the vocational resettlement on the one hand and a considerable resistance against the disabled's complete vocational and social integration on the other. 3) The degree of social distance was strongly dependent on the social situation and the type of the disability. 4) The rejection of the physically disabled seems to be mainly influenced by the following determinant psychological factors: a) the assumption that they are to blame for their disabilities b) the negative image of the disabled's personality traits, vocational performance abilities and their occupational behaviour.", "contents": "[Attitudes of gainfully employed persons towards the vocational and social integration of the physically disabled (author's transl)]. Within the framework of a representative survey 1879 gainfully employed persons - trainees, workers, employees and supervisors - were asked about their attitudes towards the vocational and social integration of the physically disabled. The article describes the following results: 1) The majority of those who responded, particularly workers in subordinate positions, were of the opinion that firms, management and co-workers were rather unwilling to accept the physically disabled as competitive and equal employees and colleagues. 2) With regard to their personal attitudes there was a striking contrast: a high general support of the vocational resettlement on the one hand and a considerable resistance against the disabled's complete vocational and social integration on the other. 3) The degree of social distance was strongly dependent on the social situation and the type of the disability. 4) The rejection of the physically disabled seems to be mainly influenced by the following determinant psychological factors: a) the assumption that they are to blame for their disabilities b) the negative image of the disabled's personality traits, vocational performance abilities and their occupational behaviour."} {"id": "PMID:158216", "title": "Expression of the Escherichia coli cell division gene sep cloned in a lambda Charon phage.", "content": "The Escherichia coli cell division gene sep, which probably codes for one of the penicillin-binding proteins, has been cloned into lambda Charon 10 to form a viable sep+ transducing phage. After infection with this hybrid phage, penicillin-binding protein 3 was overproduced and incorporated into the E. coli inner membrane.", "contents": "Expression of the Escherichia coli cell division gene sep cloned in a lambda Charon phage. The Escherichia coli cell division gene sep, which probably codes for one of the penicillin-binding proteins, has been cloned into lambda Charon 10 to form a viable sep+ transducing phage. After infection with this hybrid phage, penicillin-binding protein 3 was overproduced and incorporated into the E. coli inner membrane."} {"id": "PMID:158226", "title": "Workers' compensation program in the 1970's.", "content": "Workers' compensation has become a focus of public attention in the 1970's to a degree unprecedented in its 70-year history. Federal legislation, two national study groups, a rush of State reform amendments, and congressional hearings and bills proposing Federal standards have all contributed to the ferment of inquiry about the relevance and adequacy of the present system of State workers' compensation. Among the questions raised are: Does the system cover all the workers that should be protected? Are the benefits provided adequate? And what are the cost implications to employers of the changing program? For many years, the Social Security Administration has published estimates of the number of workers covered, the benefits paid, and the costs of workers' compensation. This article provides benchmark data to bring coverage and benefit estimates up to date and analyzes statutory provisions measuring several aspects of benefit adequacy.", "contents": "Workers' compensation program in the 1970's. Workers' compensation has become a focus of public attention in the 1970's to a degree unprecedented in its 70-year history. Federal legislation, two national study groups, a rush of State reform amendments, and congressional hearings and bills proposing Federal standards have all contributed to the ferment of inquiry about the relevance and adequacy of the present system of State workers' compensation. Among the questions raised are: Does the system cover all the workers that should be protected? Are the benefits provided adequate? And what are the cost implications to employers of the changing program? For many years, the Social Security Administration has published estimates of the number of workers covered, the benefits paid, and the costs of workers' compensation. This article provides benchmark data to bring coverage and benefit estimates up to date and analyzes statutory provisions measuring several aspects of benefit adequacy."} {"id": "PMID:158228", "title": "Melanoma development from subcellular fractions.", "content": "Amelanotic melanoma cells, RPMI-1846, were disrupted by sonic energy which caused cell membrane disruption, thereby allowing liberation of viable cellular organelles. These subcellular particles were injected into syngeneic Syrian and nonsyngeneic hamsters in six separate experiments to determine their possible growth potential. A sizable number of the injected hamsters subsequently died as a result of melanoma. In an attempt to be as certain as possible that no whole melanoma cells were injected with sonicated melanoma material, various techniques were used including collodian sections for debris analysis, phase microscopy and electron microscopy. Results of this study suggested that melanoma can be induced from particles within the melanoma cell which are liberated following cell membrane disruption. It appears that a mechanism exists for the transfer of oncogenic information that may not be dependent upon the presence of intact cells or require the participation of a viral agent.", "contents": "Melanoma development from subcellular fractions. Amelanotic melanoma cells, RPMI-1846, were disrupted by sonic energy which caused cell membrane disruption, thereby allowing liberation of viable cellular organelles. These subcellular particles were injected into syngeneic Syrian and nonsyngeneic hamsters in six separate experiments to determine their possible growth potential. A sizable number of the injected hamsters subsequently died as a result of melanoma. In an attempt to be as certain as possible that no whole melanoma cells were injected with sonicated melanoma material, various techniques were used including collodian sections for debris analysis, phase microscopy and electron microscopy. Results of this study suggested that melanoma can be induced from particles within the melanoma cell which are liberated following cell membrane disruption. It appears that a mechanism exists for the transfer of oncogenic information that may not be dependent upon the presence of intact cells or require the participation of a viral agent."} {"id": "PMID:158230", "title": "Mechanisms of the bronchoconstrictor effects of deep inspiration in asthmatic patients.", "content": "A single deep inspiration (DI) is commonly followed by transient airflow obstruction in asthmatic patients. In some patients, however, DI results in a sustained response which suggests that more than one mechanism may be responsible. We have studied the characteristics of the response to repeated DI, and their modificatiion by various pharmacological agents, by measuring specific airway resistance (sRaw) in ten subjects who showed reproducible and consistent increases in sRaw after DI. Two types of reaction were observed: type A (n = 8) had an immediate maximum and usually short persistence; type B (n = 2) had a delayed maximum with a progressive increase. In type A reactions repetition of DI showed different patterns of response--either a reproducible reaction to each DI or a plateau effect. In type B reactions the response spontaneously increased with repeated DI. Type A responses to DI were inhibited completely by a beta-adrenergic stimulant (BAS), largely by an anticholinergic drug (AC, ipratropium bromide), but in no case by disodium cromoglycate (DSCG). Type B responses were inhibited completely by BAS, largely by DSCG, and partially by AC. These findings suggest that the response to DI is due to bronchoconstriction, which in type A reactions is of reflex origin, vagally mediated, and is due in part or wholly to mediator-release in type B reactions.", "contents": "Mechanisms of the bronchoconstrictor effects of deep inspiration in asthmatic patients. A single deep inspiration (DI) is commonly followed by transient airflow obstruction in asthmatic patients. In some patients, however, DI results in a sustained response which suggests that more than one mechanism may be responsible. We have studied the characteristics of the response to repeated DI, and their modificatiion by various pharmacological agents, by measuring specific airway resistance (sRaw) in ten subjects who showed reproducible and consistent increases in sRaw after DI. Two types of reaction were observed: type A (n = 8) had an immediate maximum and usually short persistence; type B (n = 2) had a delayed maximum with a progressive increase. In type A reactions repetition of DI showed different patterns of response--either a reproducible reaction to each DI or a plateau effect. In type B reactions the response spontaneously increased with repeated DI. Type A responses to DI were inhibited completely by a beta-adrenergic stimulant (BAS), largely by an anticholinergic drug (AC, ipratropium bromide), but in no case by disodium cromoglycate (DSCG). Type B responses were inhibited completely by BAS, largely by DSCG, and partially by AC. These findings suggest that the response to DI is due to bronchoconstriction, which in type A reactions is of reflex origin, vagally mediated, and is due in part or wholly to mediator-release in type B reactions."} {"id": "PMID:158231", "title": "Cardiomegaly and heart failure in a patient with prolactin-secreting pituitary tumour.", "content": "Unexplained cardiomegaly with cardiac failure was observed in a 42-year-old woman in whom a pituitary tumour had been treated by radiotherapy five years previously. She had been amenorrhoeic for 10 years. Thyroid and adrenal function was normal. Despite treatment with digitalis and diuretic, her cardiac disease progressed until she died suddenly at the age of 45. Hyperprolactinaemia was evident some weeks before death, her serum concentration of 68 ng/ml being well above both the reported normal range (2--20 ng/ml) and the concentrations in eight female controls being treated for severe cardiac failure (5--25 ng/ml). Although the association of these two disorders might merely represent coincidence, heart disease with similar features is common in acromegaly and does not correlate with plasma growth hormone concentration. Since prolactin is known to exert metabolic growth hormone-like effects in animals and in man, the possibility should be considered that prolactin hypersecretion might induce or maintain cardiac disease in some patients with pituitary tumours. A preliminary survey of 35 subjects with hyperprolactinaemia has shown five with raised blood pressure and four, two of whom were normotensive, with cardiomegaly on chest radiography.", "contents": "Cardiomegaly and heart failure in a patient with prolactin-secreting pituitary tumour. Unexplained cardiomegaly with cardiac failure was observed in a 42-year-old woman in whom a pituitary tumour had been treated by radiotherapy five years previously. She had been amenorrhoeic for 10 years. Thyroid and adrenal function was normal. Despite treatment with digitalis and diuretic, her cardiac disease progressed until she died suddenly at the age of 45. Hyperprolactinaemia was evident some weeks before death, her serum concentration of 68 ng/ml being well above both the reported normal range (2--20 ng/ml) and the concentrations in eight female controls being treated for severe cardiac failure (5--25 ng/ml). Although the association of these two disorders might merely represent coincidence, heart disease with similar features is common in acromegaly and does not correlate with plasma growth hormone concentration. Since prolactin is known to exert metabolic growth hormone-like effects in animals and in man, the possibility should be considered that prolactin hypersecretion might induce or maintain cardiac disease in some patients with pituitary tumours. A preliminary survey of 35 subjects with hyperprolactinaemia has shown five with raised blood pressure and four, two of whom were normotensive, with cardiomegaly on chest radiography."} {"id": "PMID:158238", "title": "[Critical evaluation of the results of systematic pedodontic care].", "content": "The authors present and comment upon the clinical and radiological findings obtained from 1200 children in the framework of a caries-statistical cross-sectional study. The statistical data are subdivided into: state of oral rehabilitation, extent of oral rehabilitation, frequency of the different kinds of filling and endodontic treatment measures.", "contents": "[Critical evaluation of the results of systematic pedodontic care]. The authors present and comment upon the clinical and radiological findings obtained from 1200 children in the framework of a caries-statistical cross-sectional study. The statistical data are subdivided into: state of oral rehabilitation, extent of oral rehabilitation, frequency of the different kinds of filling and endodontic treatment measures."} {"id": "PMID:158240", "title": "Murine sera cytotoxicity toward human B cells and their effect on human mixed lymphocyte reactions.", "content": "Seven murine anti-H-2 and three nonimmune mouse sera were tested for cytotoxicity toward B and T lymphocytes from a panel of human donors. One group of sera, including two anti-H-2.33 sera, exhibited cytotoxicity directed exclusively toward human B but not T cells from all donors. Absorption studies on human lymphoblastoid cell lines (LCLs) of B or T cell origin corroborated these findings. Some nonimmune sera showed similar characteristics, indicating that the observed reactions were not attributable to cross-reactivities between mouse H-2K or D specificities and human antigens coded by the HLA-A, B, or C locus. Another set of mouse sera (anti-H-2.28b and anti-H-2.31) was highly cytotoxic to both B and T cells of some donors but not of others, suggesting that activity in these sera may arise from cross-reactions between mouse and human specifities. A third set of anti-H-2 as well as normal mouse sera showed only background cytotoxicity when tested on human cells. The ability of the B cell cytotoxic mouse sera to block the human mixed lymphocyte culture reaction (MLR) was compared to that of appropriate human alloantisera with exclusive B cell activity or a rabbit serum raised against human B cells. None of the mouse sera resulted in a significant reduction in the human MLR, whereas the human alloantisera as well as the rabbit antiserum caused a significant amount of blocking at several dilutions beyond their highest cytolytic titer.", "contents": "Murine sera cytotoxicity toward human B cells and their effect on human mixed lymphocyte reactions. Seven murine anti-H-2 and three nonimmune mouse sera were tested for cytotoxicity toward B and T lymphocytes from a panel of human donors. One group of sera, including two anti-H-2.33 sera, exhibited cytotoxicity directed exclusively toward human B but not T cells from all donors. Absorption studies on human lymphoblastoid cell lines (LCLs) of B or T cell origin corroborated these findings. Some nonimmune sera showed similar characteristics, indicating that the observed reactions were not attributable to cross-reactivities between mouse H-2K or D specificities and human antigens coded by the HLA-A, B, or C locus. Another set of mouse sera (anti-H-2.28b and anti-H-2.31) was highly cytotoxic to both B and T cells of some donors but not of others, suggesting that activity in these sera may arise from cross-reactions between mouse and human specifities. A third set of anti-H-2 as well as normal mouse sera showed only background cytotoxicity when tested on human cells. The ability of the B cell cytotoxic mouse sera to block the human mixed lymphocyte culture reaction (MLR) was compared to that of appropriate human alloantisera with exclusive B cell activity or a rabbit serum raised against human B cells. None of the mouse sera resulted in a significant reduction in the human MLR, whereas the human alloantisera as well as the rabbit antiserum caused a significant amount of blocking at several dilutions beyond their highest cytolytic titer."} {"id": "PMID:158241", "title": "Influence of blood transfusions and matching for DR antigens on kidney allograft survival in unrelated rhesus monkeys.", "content": "Kidney transplantations were performed in unrelated, immunosuppressed rhesus monkeys matched for two DR antigens and given five pretransplant transfusion of whole blood. The host-donor combinations were either reactive or nonreactive in mixed lymphocyte culture (MLC) and shared up to three A and B locus antigens with their blood and kidney donors. Although previous monkey experiments had shown a definite positive influence of DR matching as well as of pretransplant transfusions on graft survival, this was not found in the current experiments (the mean survival time for the MLC responsive group was 21.3 days for the MLC nonresponsive group 28.2 days). It appears therefore that the combination of pretransplant transfusions and matching for DR antigens does not have an additive or synergistic effect on graft survival. In fact, the prominent transfusion effect demonstrated previously may have been somehow compromised by matching for DR antigens. Alternatively, the clearly positive effect of matching for two DR antigens may have been reduced or lost as a consequence of giving the blood transfusions.", "contents": "Influence of blood transfusions and matching for DR antigens on kidney allograft survival in unrelated rhesus monkeys. Kidney transplantations were performed in unrelated, immunosuppressed rhesus monkeys matched for two DR antigens and given five pretransplant transfusion of whole blood. The host-donor combinations were either reactive or nonreactive in mixed lymphocyte culture (MLC) and shared up to three A and B locus antigens with their blood and kidney donors. Although previous monkey experiments had shown a definite positive influence of DR matching as well as of pretransplant transfusions on graft survival, this was not found in the current experiments (the mean survival time for the MLC responsive group was 21.3 days for the MLC nonresponsive group 28.2 days). It appears therefore that the combination of pretransplant transfusions and matching for DR antigens does not have an additive or synergistic effect on graft survival. In fact, the prominent transfusion effect demonstrated previously may have been somehow compromised by matching for DR antigens. Alternatively, the clearly positive effect of matching for two DR antigens may have been reduced or lost as a consequence of giving the blood transfusions."} {"id": "PMID:158243", "title": "Perception and management of guinea worm disease among Ghanaian villagers. A framework for differential health education planning.", "content": "A survey, resulted from the immediate need to understand the health behaviour of Southern Ghanaian villagers during an epidemic of guinea worm disease. While such problems are usually studied at a time when the epidemic has abated, this study emphasized getting into the field quickly to obtain data before the epidemic passed. If behaviour models are to have value for programme planning in the developing world, they should be amenable to such quick sample approaches. The study involved a survey on attitudes, beliefs and practices related to gent. Results showed distinctive and somewhat differing perceptions of susceptibility, seriousness, curability and preventability for the two ethnic groups within a single geographic area. The analysis of the survey results permitted suggestion of various educational strategies for both of the groups. This quick survey approach must be more refined before it has wide applicability. There appears to be a significant potential for developing a simplified checklist to be used by health workers in carrying a rapid educational diagnosis of a specific health problem for a given population.", "contents": "Perception and management of guinea worm disease among Ghanaian villagers. A framework for differential health education planning. A survey, resulted from the immediate need to understand the health behaviour of Southern Ghanaian villagers during an epidemic of guinea worm disease. While such problems are usually studied at a time when the epidemic has abated, this study emphasized getting into the field quickly to obtain data before the epidemic passed. If behaviour models are to have value for programme planning in the developing world, they should be amenable to such quick sample approaches. The study involved a survey on attitudes, beliefs and practices related to gent. Results showed distinctive and somewhat differing perceptions of susceptibility, seriousness, curability and preventability for the two ethnic groups within a single geographic area. The analysis of the survey results permitted suggestion of various educational strategies for both of the groups. This quick survey approach must be more refined before it has wide applicability. There appears to be a significant potential for developing a simplified checklist to be used by health workers in carrying a rapid educational diagnosis of a specific health problem for a given population."} {"id": "PMID:158244", "title": "[Role of the systems of DNA dark repair in determining bacterial and phage sensitivity to ultraviolet radiation in an ecological long-wave range].", "content": "A comparison has been made of sensitivity to far (254 nm), middle (300--315 nm) and near (315--400 nm) UV radiation of 12 strains of E. coli and 2 strains of B. subtilis differing in DNA dark repair (DR) capability. The mechanisms controlled by uvrA, uvrB, polA, recA, lon, and lexA genes are very effective in cells, irradiated by far and middle UV, but by 15--70% less effective in those irradiated by near UV. As the unirradiated bacteria poorly repair the near UV damaged phages (T7, lambda, SPPI), the low bacterial DR level after UV irradiation seems to be due to the unrepairable photoproduct formation in DNA.", "contents": "[Role of the systems of DNA dark repair in determining bacterial and phage sensitivity to ultraviolet radiation in an ecological long-wave range]. A comparison has been made of sensitivity to far (254 nm), middle (300--315 nm) and near (315--400 nm) UV radiation of 12 strains of E. coli and 2 strains of B. subtilis differing in DNA dark repair (DR) capability. The mechanisms controlled by uvrA, uvrB, polA, recA, lon, and lexA genes are very effective in cells, irradiated by far and middle UV, but by 15--70% less effective in those irradiated by near UV. As the unirradiated bacteria poorly repair the near UV damaged phages (T7, lambda, SPPI), the low bacterial DR level after UV irradiation seems to be due to the unrepairable photoproduct formation in DNA."} {"id": "PMID:158256", "title": "[Epidemiology of stomach cancer in the Kirghiz SSR].", "content": "The incidence of gastric cancer in the Republic is characterized by some features related to local natural conditions, ethnic and socio-economic factors. These features comprise variations in the gastric cancer incidence in separate climatic-geographical zones. A higher morbidity rate was noted in Chuisk valley in the north of the Republic. The lowest morbidity rate was recorded in Osha Province. The index of the gastric cancer morbidity among Russian population is higher than among Kirghiz and Uzbek nationalities. During recent years there is a tendency to the reduced morbidity and mortality due to cancer of the stomach in the Republic.", "contents": "[Epidemiology of stomach cancer in the Kirghiz SSR]. The incidence of gastric cancer in the Republic is characterized by some features related to local natural conditions, ethnic and socio-economic factors. These features comprise variations in the gastric cancer incidence in separate climatic-geographical zones. A higher morbidity rate was noted in Chuisk valley in the north of the Republic. The lowest morbidity rate was recorded in Osha Province. The index of the gastric cancer morbidity among Russian population is higher than among Kirghiz and Uzbek nationalities. During recent years there is a tendency to the reduced morbidity and mortality due to cancer of the stomach in the Republic."} {"id": "PMID:158257", "title": "[Vitamin B1, PP and C allowances of weight lifters and their requirements during training and competition periods].", "content": "Supply of the organism with vitamins C, B1 and PP during various periods of the training cycle was studied in 25 top-class athletes. All of them showed a decreased supply with vitamins, specifically low levels being recorded during competitions. Recommendations are offered with respect to dosage of the vitamins and duration of their administration in order to assist in correcting vitamin deficiency revealed.", "contents": "[Vitamin B1, PP and C allowances of weight lifters and their requirements during training and competition periods]. Supply of the organism with vitamins C, B1 and PP during various periods of the training cycle was studied in 25 top-class athletes. All of them showed a decreased supply with vitamins, specifically low levels being recorded during competitions. Recommendations are offered with respect to dosage of the vitamins and duration of their administration in order to assist in correcting vitamin deficiency revealed."} {"id": "PMID:158259", "title": "[Analysis of the copper and manganese body allowances of athletes].", "content": "Forty-eight sportswomen of various qualification and 19 women not engaged in the sports were under observation. The total losses of copper and manganese excreted with feces, urine and sweat in the sportswomen under conditions of muscular training proved higher than in the untrained women. During summer the copper and manganese content in a day diet of the sportswomen corresponded to the recommended standards while during winter the copper content was below the normal. Starting the active training in the beginner sportswomen is attended by the copper and manganese accumulation in the blood cells. Meat and weat food stuffs in the Yaroslavi region are rich in copper, with vegetable products showing the highest content of manganese, and dairy products having a low content of copper and manganese.", "contents": "[Analysis of the copper and manganese body allowances of athletes]. Forty-eight sportswomen of various qualification and 19 women not engaged in the sports were under observation. The total losses of copper and manganese excreted with feces, urine and sweat in the sportswomen under conditions of muscular training proved higher than in the untrained women. During summer the copper and manganese content in a day diet of the sportswomen corresponded to the recommended standards while during winter the copper content was below the normal. Starting the active training in the beginner sportswomen is attended by the copper and manganese accumulation in the blood cells. Meat and weat food stuffs in the Yaroslavi region are rich in copper, with vegetable products showing the highest content of manganese, and dairy products having a low content of copper and manganese."} {"id": "PMID:158260", "title": "[Isolation of strains of the Hong Kong complex (H3N2) influenza virus from Nyctalus noctula bats in Kazakhstan].", "content": "Four antigenically related hemagglutinating agents were isolated from pools of lungs and tracheas of Nyctalus noctula bats in chick embryos. Identification of the isolates by the hemagglutination inhibition, neuraminidase activity inhibition and double immunodiffusion methods revealed close antigenic relationships with A/Port Chalmers/73 virus.", "contents": "[Isolation of strains of the Hong Kong complex (H3N2) influenza virus from Nyctalus noctula bats in Kazakhstan]. Four antigenically related hemagglutinating agents were isolated from pools of lungs and tracheas of Nyctalus noctula bats in chick embryos. Identification of the isolates by the hemagglutination inhibition, neuraminidase activity inhibition and double immunodiffusion methods revealed close antigenic relationships with A/Port Chalmers/73 virus."} {"id": "PMID:158267", "title": "[The surgical treatment cavernous haemangioma of the soft tissues in the orofaciale region (author's transl)].", "content": "The experience gathered in therapy of 85 cavernous haemangioma allows to make the following conclusions: -The therapy of canernous haemangioma is very flexible. Localisation, expansion, increasing, aesthetical and functional troubles determine the indication for the therapeutical way. -Cavernous haemangioma must be operated in early infancy. The complete excision is the best method. The conservative control only with the outlook of a spontanremission is unsafe. -Big haemangioma will be treated by a combined treatment (destroying of blood vessels + surgical therapy). After injection of sclerosing solutions it is possible to exstirpate the haemangioma completely. -Extensive plastic and reconstructive operations will be done first after age of twenty years. The use of adjacent flaps shows suitable results.", "contents": "[The surgical treatment cavernous haemangioma of the soft tissues in the orofaciale region (author's transl)]. The experience gathered in therapy of 85 cavernous haemangioma allows to make the following conclusions: -The therapy of canernous haemangioma is very flexible. Localisation, expansion, increasing, aesthetical and functional troubles determine the indication for the therapeutical way. -Cavernous haemangioma must be operated in early infancy. The complete excision is the best method. The conservative control only with the outlook of a spontanremission is unsafe. -Big haemangioma will be treated by a combined treatment (destroying of blood vessels + surgical therapy). After injection of sclerosing solutions it is possible to exstirpate the haemangioma completely. -Extensive plastic and reconstructive operations will be done first after age of twenty years. The use of adjacent flaps shows suitable results."} {"id": "PMID:158268", "title": "[Changes at different ages in the epithelium of the human oral mucosa of the hard palate and cheek (author's transl)].", "content": "This paper describes the results of observation by optical microscopy of the changes in structure of the epithelium of the human oral mucous membrane between birth and old age. The intraepithelial regulatory mechanism of the oral mucous membrane can be disturbed by exogenous and endogenous factors, as a result of which it is possible for the mucosa to lose part of its resistance to external influences. Sex hormones are considered to play an important role in this connection. In the intrauterine state, the epithelium has no stratum corneum. However, a stratum corneum can be seen to develop, in the form of a parakeratosis, already shortly after birth. During puberty, there is observed the capacity to develop, on the palate and gingiva, a protective layer of anuclear horny lumps. At the beginning of the climacteric, the palatal epithelium can be seen to undergo changes in the direction of the prepuberal condition or intermediate stages. The buccal epithelium is invariably free from keratinization and does not usually show such pronounced changes with aging.", "contents": "[Changes at different ages in the epithelium of the human oral mucosa of the hard palate and cheek (author's transl)]. This paper describes the results of observation by optical microscopy of the changes in structure of the epithelium of the human oral mucous membrane between birth and old age. The intraepithelial regulatory mechanism of the oral mucous membrane can be disturbed by exogenous and endogenous factors, as a result of which it is possible for the mucosa to lose part of its resistance to external influences. Sex hormones are considered to play an important role in this connection. In the intrauterine state, the epithelium has no stratum corneum. However, a stratum corneum can be seen to develop, in the form of a parakeratosis, already shortly after birth. During puberty, there is observed the capacity to develop, on the palate and gingiva, a protective layer of anuclear horny lumps. At the beginning of the climacteric, the palatal epithelium can be seen to undergo changes in the direction of the prepuberal condition or intermediate stages. The buccal epithelium is invariably free from keratinization and does not usually show such pronounced changes with aging."} {"id": "PMID:158269", "title": "[Investigations into ways of improving the ultimate strength of ceramic dental materials (author's transl)].", "content": "Despite major improvements, ceramic dental materials, as albite glasses, still show unsatisfactory strength properties. It has been found that the combination of Keradens type dentinal compounds with aluminum-oxide-containing core materials, because of internal stresses, results in a higher ultimate strength than is suggested by the strength values of the single components. In addition, it has been found that wetting the surface of the ceramic test specimen results in a significant decrease in ultimate strength.", "contents": "[Investigations into ways of improving the ultimate strength of ceramic dental materials (author's transl)]. Despite major improvements, ceramic dental materials, as albite glasses, still show unsatisfactory strength properties. It has been found that the combination of Keradens type dentinal compounds with aluminum-oxide-containing core materials, because of internal stresses, results in a higher ultimate strength than is suggested by the strength values of the single components. In addition, it has been found that wetting the surface of the ceramic test specimen results in a significant decrease in ultimate strength."} {"id": "PMID:158270", "title": "[Studies of parodontal results obtained for selected teeth and groups of teeth with particular reference to their predictive potential regarding an overall assessment (author's transl)].", "content": "With the support of a Cluster Analysis and other statistical methods we have found out the relative efficiency of some periodontal partial recording selections. Overrating or underrating evaluations arise from the registration of periodontal symptoms and signs by partial recording of special teeth or groups of teeth. The results of our investigations have demonstrated the higher quantitative and qualitative coincidence of the RAMFJORDS teeth with the periodontal status as the frontal region of the lower jaw.", "contents": "[Studies of parodontal results obtained for selected teeth and groups of teeth with particular reference to their predictive potential regarding an overall assessment (author's transl)]. With the support of a Cluster Analysis and other statistical methods we have found out the relative efficiency of some periodontal partial recording selections. Overrating or underrating evaluations arise from the registration of periodontal symptoms and signs by partial recording of special teeth or groups of teeth. The results of our investigations have demonstrated the higher quantitative and qualitative coincidence of the RAMFJORDS teeth with the periodontal status as the frontal region of the lower jaw."} {"id": "PMID:158271", "title": "[The preparation trauma of the pulp and its reactive behavior (author's transl)].", "content": "The postpreparative pathophysiological reactions of the blood circulation are shown by vital microscopy examinations of the pulp of the incisors of living rats.--After twenty-four hours from the experimental preparation of cavities, functional changes are characterized by acutely inflammatory reactions. With the passage of time (seven-day check), the damage is compensated for by extensive regeneration (re-formation and new formation of vessels, functional adaptation of the circulation of blood, anastomosing), although irreversible alterations can be seen to remain in the incisors of rats.--A comparison with the results of histological reexaminations of human teeth shows that careful preparation usually avoids lesions being left behind after the fading away of localized acute inflammations.", "contents": "[The preparation trauma of the pulp and its reactive behavior (author's transl)]. The postpreparative pathophysiological reactions of the blood circulation are shown by vital microscopy examinations of the pulp of the incisors of living rats.--After twenty-four hours from the experimental preparation of cavities, functional changes are characterized by acutely inflammatory reactions. With the passage of time (seven-day check), the damage is compensated for by extensive regeneration (re-formation and new formation of vessels, functional adaptation of the circulation of blood, anastomosing), although irreversible alterations can be seen to remain in the incisors of rats.--A comparison with the results of histological reexaminations of human teeth shows that careful preparation usually avoids lesions being left behind after the fading away of localized acute inflammations."} {"id": "PMID:158266", "title": "[Effect of serotonin on processes of elaboration and fixation of heterogeneous temporary connections].", "content": "The effect of serotonin (5-OT) level in the brain on the elaboration and retention of heterogenous conditioned reflexes was studied in the experiments on rats and mice. Redundancy of 5-OT deteriorated the retention of defensive and alimentary conditioned reflexes and almost fully prevented the fixation of drinking conditioned reflexes. The reduction of 5-OT led to less pronounced disorders in the retention of conditioned reflexes. With a prolonged delay of electrocutaneous reinforcement (from 5 to 10 s) the control animals showed slower elaboration of two-side avoidance reflexes, while their retention was uneffected. The redundancy of 5-OT in these conditions accelerated the elaboration but at the same time deteriorated the retention as in case of 5-second delay. A conclusion is made that with the changed level of 5-OT the impairment of conditioned reflexes retention doesn't depend on the changes in the speed of their elaboration. The \"point of application\" of changes in 5-OT content lies in the process of the temporary connection consolidation. The degree of 5-OT participation in these processes depends on the characteristics of elaborated conditioned reflexes.", "contents": "[Effect of serotonin on processes of elaboration and fixation of heterogeneous temporary connections]. The effect of serotonin (5-OT) level in the brain on the elaboration and retention of heterogenous conditioned reflexes was studied in the experiments on rats and mice. Redundancy of 5-OT deteriorated the retention of defensive and alimentary conditioned reflexes and almost fully prevented the fixation of drinking conditioned reflexes. The reduction of 5-OT led to less pronounced disorders in the retention of conditioned reflexes. With a prolonged delay of electrocutaneous reinforcement (from 5 to 10 s) the control animals showed slower elaboration of two-side avoidance reflexes, while their retention was uneffected. The redundancy of 5-OT in these conditions accelerated the elaboration but at the same time deteriorated the retention as in case of 5-second delay. A conclusion is made that with the changed level of 5-OT the impairment of conditioned reflexes retention doesn't depend on the changes in the speed of their elaboration. The \"point of application\" of changes in 5-OT content lies in the process of the temporary connection consolidation. The degree of 5-OT participation in these processes depends on the characteristics of elaborated conditioned reflexes."} {"id": "PMID:158272", "title": "[On the acid solubility of the dental enamel of rabbits after internal administration of various antibiotic substances (author's transl)].", "content": "Sections of etched enamel and dentinal surfaces were examined to compare the acid solubility of normal hard tissue and determine the effects of various antibiotic substances. Considerable differences were observed, of which the correlation with cariogenesis and with the progression of caries are being discussed in detail. The results of this study show that treatment with antibiotics may lead to reductions in quality in infants, young children, and nursing mothers.", "contents": "[On the acid solubility of the dental enamel of rabbits after internal administration of various antibiotic substances (author's transl)]. Sections of etched enamel and dentinal surfaces were examined to compare the acid solubility of normal hard tissue and determine the effects of various antibiotic substances. Considerable differences were observed, of which the correlation with cariogenesis and with the progression of caries are being discussed in detail. The results of this study show that treatment with antibiotics may lead to reductions in quality in infants, young children, and nursing mothers."} {"id": "PMID:158280", "title": "Mode of action of dantrolene sodium in spasticity.", "content": "The mode of action of dantrolene sodium was studied in 11 multiple sclerosis patients with spastic paresis of the legs by measurements of changes in electromyographic and mechanomyographic proprioceptive reflex responses and in voluntary power. Dantrolene sodium 0.5 mg per kg body weight given intravenously clearly reduced monosynaptic reflex twitch tension, but voluntary power only moderately so. The electromyographic reflex responses were unchanged or slightly increased. The mode of action of the drug on spindle function is discussed on the basis of the present findings and the literature. It is concluded that dantrolene sodium does not reduce spindle stretch sensitivity, but probably reduces activity in group II and tonic 1a afferent fibers.", "contents": "Mode of action of dantrolene sodium in spasticity. The mode of action of dantrolene sodium was studied in 11 multiple sclerosis patients with spastic paresis of the legs by measurements of changes in electromyographic and mechanomyographic proprioceptive reflex responses and in voluntary power. Dantrolene sodium 0.5 mg per kg body weight given intravenously clearly reduced monosynaptic reflex twitch tension, but voluntary power only moderately so. The electromyographic reflex responses were unchanged or slightly increased. The mode of action of the drug on spindle function is discussed on the basis of the present findings and the literature. It is concluded that dantrolene sodium does not reduce spindle stretch sensitivity, but probably reduces activity in group II and tonic 1a afferent fibers."} {"id": "PMID:158281", "title": "Matrix formation in the mandibular condyle of the rat (35S) - sulfate incorporation studies.", "content": "The matrix formation activity of the mandibular condylar cartilage was investigated using radioactive sulfate incorporation. The condylar cartilage was studied at various developmental stages; as an autotransplant, in situ and on a chemically defined medium. An initial decrease in the cpm/DNA was followed by an increase, until a maximum was attained for all groups, between the 14th and 17th days. Thereafter, the matrix formation activity decreased. There was a surprising likeness in the patterns of activity for all the samples investigated. This tends to support the hypothesis that cartilagenous growth seem to be regulated, at least to some extent by one or more humoral factors.", "contents": "Matrix formation in the mandibular condyle of the rat (35S) - sulfate incorporation studies. The matrix formation activity of the mandibular condylar cartilage was investigated using radioactive sulfate incorporation. The condylar cartilage was studied at various developmental stages; as an autotransplant, in situ and on a chemically defined medium. An initial decrease in the cpm/DNA was followed by an increase, until a maximum was attained for all groups, between the 14th and 17th days. Thereafter, the matrix formation activity decreased. There was a surprising likeness in the patterns of activity for all the samples investigated. This tends to support the hypothesis that cartilagenous growth seem to be regulated, at least to some extent by one or more humoral factors."} {"id": "PMID:158283", "title": "Cytostatic effect on tumour cells induced in human monocytes by mediators from BCG-stimulated lymphocytes and MLC.", "content": "Human monocytes activated by mediators (lymphokines) from BCG-stimulated, sensitized lymphocytes (from BCG-vaccinated donors) were cytostatic to a human cell line. Mediators from allogeneic lymphocytes activated the cytostatic ability of monocytes to the same degree as mediators from autologous lymphocytes. Mediators from BCG-stimulated lymphocytes from tuberculin-negative donors not vaccinated with BCG, activated the monocytes only to a small extent. Culture of lymphocytes in a membrane chamber (MC) proximate to monocytes, or incubation of monocytes with filtered supernatants of lymphocyte cultures, were equally effective procedures for inducing cytostatic ability in monocytes. Supernatants of sensitized lymphocytes cultured on BCG for four hours did not activate the monocytes, while supernatants collected after 24 hours activated the cytostatic ability to the same extent as 72-hour supernatants. Supernatants of mixed lymphocyte cultures (MLC) collected after 24 hours did not activate the monocyte cytostatic ability at all. Forty-eight and 72-hour supernatants of MLC showed a small but increasing activity. There was no significant difference between BCG-stimulated lymphocytes and MLC in their maximum DNA synthesis or in the kinetics of their DNA synthesis. Thus, the DNA synthesis and secretion of lymphocyte mediators may be independent phenomena resulting from the same stimulus.", "contents": "Cytostatic effect on tumour cells induced in human monocytes by mediators from BCG-stimulated lymphocytes and MLC. Human monocytes activated by mediators (lymphokines) from BCG-stimulated, sensitized lymphocytes (from BCG-vaccinated donors) were cytostatic to a human cell line. Mediators from allogeneic lymphocytes activated the cytostatic ability of monocytes to the same degree as mediators from autologous lymphocytes. Mediators from BCG-stimulated lymphocytes from tuberculin-negative donors not vaccinated with BCG, activated the monocytes only to a small extent. Culture of lymphocytes in a membrane chamber (MC) proximate to monocytes, or incubation of monocytes with filtered supernatants of lymphocyte cultures, were equally effective procedures for inducing cytostatic ability in monocytes. Supernatants of sensitized lymphocytes cultured on BCG for four hours did not activate the monocytes, while supernatants collected after 24 hours activated the cytostatic ability to the same extent as 72-hour supernatants. Supernatants of mixed lymphocyte cultures (MLC) collected after 24 hours did not activate the monocyte cytostatic ability at all. Forty-eight and 72-hour supernatants of MLC showed a small but increasing activity. There was no significant difference between BCG-stimulated lymphocytes and MLC in their maximum DNA synthesis or in the kinetics of their DNA synthesis. Thus, the DNA synthesis and secretion of lymphocyte mediators may be independent phenomena resulting from the same stimulus."} {"id": "PMID:158284", "title": "The human mixed lymphocyte reaction responder and stimulator capacities of highly purified T- and non-T cells and the role of monocytes.", "content": "E-rosette sedimentation with AET treated sheep red blood cells and human lymphocytes provieded a source of highly purified T- and non-T cells. Together with unseparated cells these were tested for responder and stimulator capacities in the mixed lymphocyte reaction, and it was found that the non-T cells were weak, but consistent responders only when T cells were present as stimulators. On the other hand, T-T combinations always exhibited weak proliferation demonstrating that T cells possess stimulator capacities. Adherent cells grown on Petri dishes were found to exert a dual function: as helper cells in low, and suppressor cells in high concentrations.", "contents": "The human mixed lymphocyte reaction responder and stimulator capacities of highly purified T- and non-T cells and the role of monocytes. E-rosette sedimentation with AET treated sheep red blood cells and human lymphocytes provieded a source of highly purified T- and non-T cells. Together with unseparated cells these were tested for responder and stimulator capacities in the mixed lymphocyte reaction, and it was found that the non-T cells were weak, but consistent responders only when T cells were present as stimulators. On the other hand, T-T combinations always exhibited weak proliferation demonstrating that T cells possess stimulator capacities. Adherent cells grown on Petri dishes were found to exert a dual function: as helper cells in low, and suppressor cells in high concentrations."} {"id": "PMID:158285", "title": "Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. II. Changes in the areal density of cytoplasmic vacuoles and in the subcellular localization of acid phosphatase.", "content": "H-2b lymphocytes were sensitized against H-2d alloantigens by lymphocyte culture reaction and incubated with H-2d mastocytoma cells. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal density of the cytoplasmic vacuoles as well as the subcellular localization of acid phosphatase in lymphocytes were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed change following interaction with target cells. The vacuole area in percent of cytoplasmic area (vacuole areal density) of sensitized lymphoblasts increased during the first 30 minutes and from the third to fourth hour of interaction with target cells. Acid phosphatase staining was observed in the Golgi apparatus of the lymphoblasts after 30 minutes of interaction. Multivesicular bodies showed acid phosphatase staining within 20 minutes of interaction with target cells. After 20 minutes of interaction, phagosomes containing myelin figures were formed. These phagosomes also showed acid phosphatase staining and during the next hours of interaction their number increased over the number of multivesicular bodies.", "contents": "Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. II. Changes in the areal density of cytoplasmic vacuoles and in the subcellular localization of acid phosphatase. H-2b lymphocytes were sensitized against H-2d alloantigens by lymphocyte culture reaction and incubated with H-2d mastocytoma cells. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal density of the cytoplasmic vacuoles as well as the subcellular localization of acid phosphatase in lymphocytes were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed change following interaction with target cells. The vacuole area in percent of cytoplasmic area (vacuole areal density) of sensitized lymphoblasts increased during the first 30 minutes and from the third to fourth hour of interaction with target cells. Acid phosphatase staining was observed in the Golgi apparatus of the lymphoblasts after 30 minutes of interaction. Multivesicular bodies showed acid phosphatase staining within 20 minutes of interaction with target cells. After 20 minutes of interaction, phagosomes containing myelin figures were formed. These phagosomes also showed acid phosphatase staining and during the next hours of interaction their number increased over the number of multivesicular bodies."} {"id": "PMID:158298", "title": "An assessment of occupational therapists' roles and attitudes toward sexual rehabilitation of the disabled.", "content": "Sexual adjustment is believed to be a fundamental aspect of the medical and psychosocial rehabilitation of the disabled and chronically ill. A sample of 26 occupational therapists involved in adult rehabilitation services were given a list of specific tasks identified in the literature to be related to medical (physical) aspects of sexual rehabilitation. The results indicated that a small percentage of occupational therapists participate in these tasks. The majority believed that the tasks were important in occupational therapy but that their preparation to perform the tasks was inadequate. The subjects, as a group, held positive attitudes toward sexual rehabilitation and considered it a legitimate aspect of health care for which an appropriate content should be integrated into the basic curricula in occupational therapy.", "contents": "An assessment of occupational therapists' roles and attitudes toward sexual rehabilitation of the disabled. Sexual adjustment is believed to be a fundamental aspect of the medical and psychosocial rehabilitation of the disabled and chronically ill. A sample of 26 occupational therapists involved in adult rehabilitation services were given a list of specific tasks identified in the literature to be related to medical (physical) aspects of sexual rehabilitation. The results indicated that a small percentage of occupational therapists participate in these tasks. The majority believed that the tasks were important in occupational therapy but that their preparation to perform the tasks was inadequate. The subjects, as a group, held positive attitudes toward sexual rehabilitation and considered it a legitimate aspect of health care for which an appropriate content should be integrated into the basic curricula in occupational therapy."} {"id": "PMID:158299", "title": "Occupational therapy roles and functions in the education of the school-based handicapped student.", "content": "This article presents current roles and functions of the school-based occupational therapist that were identified through data analyses of surveys conducted during 1978. The major roles emerging from data are evaluation/screening, program planning, implementing intervention programs, supervision, and consultation. Functions of occupational therapy educational management for each of the roles are specified. The findings will be used in the development of competency-based educational programs to prepare the occupational therapist with the specialized competencies needed in the provision of services within school systems.", "contents": "Occupational therapy roles and functions in the education of the school-based handicapped student. This article presents current roles and functions of the school-based occupational therapist that were identified through data analyses of surveys conducted during 1978. The major roles emerging from data are evaluation/screening, program planning, implementing intervention programs, supervision, and consultation. Functions of occupational therapy educational management for each of the roles are specified. The findings will be used in the development of competency-based educational programs to prepare the occupational therapist with the specialized competencies needed in the provision of services within school systems."} {"id": "PMID:158301", "title": "Comparison of the size of the arterial vascular bed to the right ventricular mass in patients with chronic obstructive pulmonary disease.", "content": "Hearts from patients dying with severe chronic obstructive pulmonary disease were examined for right ventricular mass and coronary arterial vascular bed size. Normal hearts obtained from patients dying of other causes were also examined for comparison. The relationship between the size of the vascular bed and ventricular mass was examined and a definite but low correlation was found. Severe obstructive coronary artery disease was excluded, and chronic hypoxemia did not alter the results. The arterial vascular bed supplying the right ventricle of male patients with severe chronic obstructive pulmonary disease appears to undergo a compensatory increase in size as the ventricular mass enlarges, but this is highly variable and incomplete.", "contents": "Comparison of the size of the arterial vascular bed to the right ventricular mass in patients with chronic obstructive pulmonary disease. Hearts from patients dying with severe chronic obstructive pulmonary disease were examined for right ventricular mass and coronary arterial vascular bed size. Normal hearts obtained from patients dying of other causes were also examined for comparison. The relationship between the size of the vascular bed and ventricular mass was examined and a definite but low correlation was found. Severe obstructive coronary artery disease was excluded, and chronic hypoxemia did not alter the results. The arterial vascular bed supplying the right ventricle of male patients with severe chronic obstructive pulmonary disease appears to undergo a compensatory increase in size as the ventricular mass enlarges, but this is highly variable and incomplete."} {"id": "PMID:158305", "title": "Myocardial oxygen supply in left ventricular hypertrophy and coronary heart disease.", "content": "Coronary arteriolar dilation adjusts blood flow according to local fluctuating metabolic needs of the myocardium. Because of high extravascular compression during systole, the subendocardial layer of the left ventricle is especially dependent on the duration and the perfusion pressure of the diastolic period. In patients with obstructive coronary artery disease, regional arteriolar dilation is utilized to compensate for focal arterial stenoses. Coronary blood flow may be compensated with the patient at rest, but loss of reserve arteriolar dilation limits further adjustment to superimposed transient increases in metabolic needs. Subendocardial perfusion in the region supplied by the stenosed artery is especially vulnerable to shortened diastolic time during tachycardia. In patients with chronic aortic valve disease, the metabolic rate of the left ventricle is increased in proportion to the increases in myocardial mass and work. Coronary blood flow and metabolic rate per gram of the hypertrophied myocardium are normal when the patient is at rest, at the expense of diminished coronary arteriolar reserve. High tissue pressure relative to the diastolic perfusion pressure probably contributes to the diffuse subendocardial ischemia that occurs in these patients during tachycardia.", "contents": "Myocardial oxygen supply in left ventricular hypertrophy and coronary heart disease. Coronary arteriolar dilation adjusts blood flow according to local fluctuating metabolic needs of the myocardium. Because of high extravascular compression during systole, the subendocardial layer of the left ventricle is especially dependent on the duration and the perfusion pressure of the diastolic period. In patients with obstructive coronary artery disease, regional arteriolar dilation is utilized to compensate for focal arterial stenoses. Coronary blood flow may be compensated with the patient at rest, but loss of reserve arteriolar dilation limits further adjustment to superimposed transient increases in metabolic needs. Subendocardial perfusion in the region supplied by the stenosed artery is especially vulnerable to shortened diastolic time during tachycardia. In patients with chronic aortic valve disease, the metabolic rate of the left ventricle is increased in proportion to the increases in myocardial mass and work. Coronary blood flow and metabolic rate per gram of the hypertrophied myocardium are normal when the patient is at rest, at the expense of diminished coronary arteriolar reserve. High tissue pressure relative to the diastolic perfusion pressure probably contributes to the diffuse subendocardial ischemia that occurs in these patients during tachycardia."} {"id": "PMID:158306", "title": "Occurrence and distribution of muscle spindles in masticatory and suprahyoid muscles of the rat.", "content": "The occurrence and distribution of muscle spindles was studied in histochemically and conventionally stained serial cross sections of 6-week-old and adult rat masticatory and suprahyoid muscles. Spindles were present in moderate to large numbers in jaw closers, but they were absent in jaw openers and two of four muscles of an accessory suprahyoid group. In jaw closers, 67% or more of the total spindle population was concentrated relatively distant from the temporomandibular joint, in muscle portions which contained large numbers of extrafusal fibers reacting strongly for oxidative enzymes. Because of their location, spindles in these portions should be stretched more and, subsequently, should respond with a greater afferent discharge at any given muscle length than spindles situated nearer to the joint. Spindles in jaw closers, especially the medial pterygoid and deep masseter, often occurred in clusters and complex forms near the terminal branching of intramuscular nerve trunks. No such concentrations were seen in the two muscles of the accessory suprahyoid group that had spindles. The association in jaw closers of spindles with extrafusal fibers high in oxidative enzyme activity is consistent with the view that spindles are the sensory component of a reflex system that recruits these fibers for finely-graded contractions in response to small internal length-changes of the muscle (Botterman et al., '78); however, in jaw openers and two muscles of the accessory suprahyoid group, the absence of spindles, coupled with the presence of large populations of extrafusal fibers high in oxidative enzyme activity, is not easily reconciled with this concept.", "contents": "Occurrence and distribution of muscle spindles in masticatory and suprahyoid muscles of the rat. The occurrence and distribution of muscle spindles was studied in histochemically and conventionally stained serial cross sections of 6-week-old and adult rat masticatory and suprahyoid muscles. Spindles were present in moderate to large numbers in jaw closers, but they were absent in jaw openers and two of four muscles of an accessory suprahyoid group. In jaw closers, 67% or more of the total spindle population was concentrated relatively distant from the temporomandibular joint, in muscle portions which contained large numbers of extrafusal fibers reacting strongly for oxidative enzymes. Because of their location, spindles in these portions should be stretched more and, subsequently, should respond with a greater afferent discharge at any given muscle length than spindles situated nearer to the joint. Spindles in jaw closers, especially the medial pterygoid and deep masseter, often occurred in clusters and complex forms near the terminal branching of intramuscular nerve trunks. No such concentrations were seen in the two muscles of the accessory suprahyoid group that had spindles. The association in jaw closers of spindles with extrafusal fibers high in oxidative enzyme activity is consistent with the view that spindles are the sensory component of a reflex system that recruits these fibers for finely-graded contractions in response to small internal length-changes of the muscle (Botterman et al., '78); however, in jaw openers and two muscles of the accessory suprahyoid group, the absence of spindles, coupled with the presence of large populations of extrafusal fibers high in oxidative enzyme activity, is not easily reconciled with this concept."} {"id": "PMID:158307", "title": "The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts.", "content": "In addition to direct gene dosage effects, the deleterious phenotypic consequences of aneuploidy may result from secondary regulatory effects on the production and degradation of gene products coded for by other chromosomes. In an initial test of the hypothesis that extensive secondary effects play an important role in the phenotypic consequences of aneuploidy, we have used two-dimensional gel electrophoresis with radioautography to look for such secondary effects among the polypeptides synthesized by human fibroblasts grown in vitro. The polypeptide patterns of fibroblast strains from four trisomy 21 subjects and one trisomy 21/normal mosaic were compared to those from five matched normal subjects. Of approximately 850 polypeptides visualized, only four show a pattern of variation which may be related to trisomy 21. Additional differences in polypeptide concentrations were found among the strains, attributable to genetic heterogeneity between donor individuals and differences in tissue of origin. These results indicate that, at least in fibroblasts in vitro, trisomy 21 does not cause major regulatory changes in the rates of production and degradation of a large number of polypeptides.", "contents": "The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts. In addition to direct gene dosage effects, the deleterious phenotypic consequences of aneuploidy may result from secondary regulatory effects on the production and degradation of gene products coded for by other chromosomes. In an initial test of the hypothesis that extensive secondary effects play an important role in the phenotypic consequences of aneuploidy, we have used two-dimensional gel electrophoresis with radioautography to look for such secondary effects among the polypeptides synthesized by human fibroblasts grown in vitro. The polypeptide patterns of fibroblast strains from four trisomy 21 subjects and one trisomy 21/normal mosaic were compared to those from five matched normal subjects. Of approximately 850 polypeptides visualized, only four show a pattern of variation which may be related to trisomy 21. Additional differences in polypeptide concentrations were found among the strains, attributable to genetic heterogeneity between donor individuals and differences in tissue of origin. These results indicate that, at least in fibroblasts in vitro, trisomy 21 does not cause major regulatory changes in the rates of production and degradation of a large number of polypeptides."} {"id": "PMID:158308", "title": "Paternal age and Down syndrome.", "content": "The frequency of Down syndrome (DS) in infants of older fathers has been examined in two sets of data. The effect of maternal age was controlled by single years of age. Lack of tight control has been an important weakness of other studies on this subject. Data obtained in metropolitan Atlanta by an intensive case-ascertainment program showed no overall excess of DS infants born to older fathers. Nor was there evidence of such an effect in recent birth certificate data made available by the National Center for Health Statistics. The Atlanta data suggest an increased number of DS infants born to older fathers who had children by women less than or equal to 34 years. However, there was a small deficiency of DS infants born to older fathers by women greater than or equal to 35 years. The possibility of a paternal-age effect remains open, but the available data suggest that, if it exists, it is quite small.", "contents": "Paternal age and Down syndrome. The frequency of Down syndrome (DS) in infants of older fathers has been examined in two sets of data. The effect of maternal age was controlled by single years of age. Lack of tight control has been an important weakness of other studies on this subject. Data obtained in metropolitan Atlanta by an intensive case-ascertainment program showed no overall excess of DS infants born to older fathers. Nor was there evidence of such an effect in recent birth certificate data made available by the National Center for Health Statistics. The Atlanta data suggest an increased number of DS infants born to older fathers who had children by women less than or equal to 34 years. However, there was a small deficiency of DS infants born to older fathers by women greater than or equal to 35 years. The possibility of a paternal-age effect remains open, but the available data suggest that, if it exists, it is quite small."} {"id": "PMID:158309", "title": "The distorted shell method for clustering for syndrome classification.", "content": "Syndrome classification may be described as the arrangement of individuals into groups on the basis of their phenotypic resemblance. This paper describes how phenotypic resemblance may be quantified and demonstrates a numerical method called distorted shell clustering, which isolates groups of phenotypically similar individuals representing syndromes. This new method takes into consideration apparent biological properties of syndromes. It allows for overlapping phenotypes between syndromes, and differing character association and variability within syndromes. This method is compared to four other clustering methods by using suspects for a syndrome of known etiology (Down syndrome). The numerical results based on the phenotype then can be compared with the actual diagnosis. Only the distorted shell method classifies patients, without error, into two major clusters: the Down and the non-Down, while maintaining a high level of efficiency.", "contents": "The distorted shell method for clustering for syndrome classification. Syndrome classification may be described as the arrangement of individuals into groups on the basis of their phenotypic resemblance. This paper describes how phenotypic resemblance may be quantified and demonstrates a numerical method called distorted shell clustering, which isolates groups of phenotypically similar individuals representing syndromes. This new method takes into consideration apparent biological properties of syndromes. It allows for overlapping phenotypes between syndromes, and differing character association and variability within syndromes. This method is compared to four other clustering methods by using suspects for a syndrome of known etiology (Down syndrome). The numerical results based on the phenotype then can be compared with the actual diagnosis. Only the distorted shell method classifies patients, without error, into two major clusters: the Down and the non-Down, while maintaining a high level of efficiency."} {"id": "PMID:158311", "title": "Performance characteristics of preschool Down's syndrome children receiving augmented or repetitive verbal instruction.", "content": "Young Down's syndrome children were compared on their ability to respond to typical preschool learning tasks when given either augmented or repetitive verbal instruction. Augmented verbal instruction began with (a) a verbal prompt followed, as needed, by (b) verbal instruction, (c) verbal instruction plus modeling, and (d) verbal instruction plus manual guidance. Repeated verbal instruction involved the verbal repetition of task directions up to three times after the initial verbal prompt. A groups of age-matched nonretarded children served as a contrast group. Results indicated that Down's syndrome children experienced serious acquisition problems despite either the augmented verbal-instruction series or the repeated verbal-instruction series.", "contents": "Performance characteristics of preschool Down's syndrome children receiving augmented or repetitive verbal instruction. Young Down's syndrome children were compared on their ability to respond to typical preschool learning tasks when given either augmented or repetitive verbal instruction. Augmented verbal instruction began with (a) a verbal prompt followed, as needed, by (b) verbal instruction, (c) verbal instruction plus modeling, and (d) verbal instruction plus manual guidance. Repeated verbal instruction involved the verbal repetition of task directions up to three times after the initial verbal prompt. A groups of age-matched nonretarded children served as a contrast group. Results indicated that Down's syndrome children experienced serious acquisition problems despite either the augmented verbal-instruction series or the repeated verbal-instruction series."} {"id": "PMID:158312", "title": "Incidence of pain among women undergoing laparoscopic sterilization by electrocoagulation, the spring-loaded clip, and the tubal ring.", "content": "Data analyzed from five comparative studies show a relationship between the technique of tubal occlusion and pain experienced by patients both at the time of the procedure and during the recovery period. During the procedure, the spring-loaded clip is the technique least likely and the tubal ring the technique most likely to be associated with pain. During the recovery period, both the spring-loaded clip and the tubal ring are associated with higher rates of abdominal or pelvic pain than is electrocoagulation. Differences in pain that occurred during the recovery period did not persist to the early follow-up visit.", "contents": "Incidence of pain among women undergoing laparoscopic sterilization by electrocoagulation, the spring-loaded clip, and the tubal ring. Data analyzed from five comparative studies show a relationship between the technique of tubal occlusion and pain experienced by patients both at the time of the procedure and during the recovery period. During the procedure, the spring-loaded clip is the technique least likely and the tubal ring the technique most likely to be associated with pain. During the recovery period, both the spring-loaded clip and the tubal ring are associated with higher rates of abdominal or pelvic pain than is electrocoagulation. Differences in pain that occurred during the recovery period did not persist to the early follow-up visit."} {"id": "PMID:158314", "title": "Ocular rosacea.", "content": "Ocular rosacea was diagnosed in 49 patients. The most common signs and symptoms were foreign body sensation, burning, superficial punctate erosions, chalazia, and belpharitis. Less common but dangerous to the vision was corneal thinning, vascularization, and infiltrates. Three new associated symptoms were found. These were mapdot subepithelial opacities, recurrent erosions, and moderately severe foreign body sensation, pain or burning with minimal associated signs. Of the 49 patients, 37 were treated with 250 mg of oral tetracycline four times a day, which resulted in improvement in almost all patients from four to 17 days after initiation of therapy. Most of the patients have been able to taper, or taper and stop therapy without recurrence of their symptoms. Those patients with foreign body sensation, burning, and pain required the most prolonged therapy in order to taper or stop treatment with tetracycline.", "contents": "Ocular rosacea. Ocular rosacea was diagnosed in 49 patients. The most common signs and symptoms were foreign body sensation, burning, superficial punctate erosions, chalazia, and belpharitis. Less common but dangerous to the vision was corneal thinning, vascularization, and infiltrates. Three new associated symptoms were found. These were mapdot subepithelial opacities, recurrent erosions, and moderately severe foreign body sensation, pain or burning with minimal associated signs. Of the 49 patients, 37 were treated with 250 mg of oral tetracycline four times a day, which resulted in improvement in almost all patients from four to 17 days after initiation of therapy. Most of the patients have been able to taper, or taper and stop therapy without recurrence of their symptoms. Those patients with foreign body sensation, burning, and pain required the most prolonged therapy in order to taper or stop treatment with tetracycline."} {"id": "PMID:158315", "title": "Normative data on low back mobility and activity levels. Implications for neuromuscular reeducation.", "content": "Low back mobility and electromyographic movements were performed in 121 normal subjects, grouped by age and sex. Women tended to show greater ranges of motion for straight leg raising, trunk rotation and lateral bending while vertebral separation (forward flexion) was greater in men. A sex-age interaction was observed only in lateral bending, thus implying that for other mobility measurements, data within the age groupings employed in this study can be combined for men and women. Electromyographic data were integrated and quantified using EMG biofeedback equipment for unilateral or bilateral recordings made primarily from the erector spinae muscle between lumbar 3-4 and lumbar 4-5 levels, three centimeters lateral to the spinous processes. Dynamic (trunk flexion-extension, lateral rotation-standing, stooping) and static (quiet sitting, rotation-sitting) movements were performed over a ten second interval. Data analyses verified previous electromyographic studies by demonstrating the trunk extensor function of the erector spinae and the relatively greater unilateral activity when turning to the opposite direction in the erect posture. EMG silence was seen during full trunk flexion. Noticeable sex-age interaction were observed for all dynamic movements but not for static activities. Therefore, it is suggested that EMG data during dynamic movements in a normal population cannot be grouped for men and women within a specified age distribution. These data represent one series of baselines to which mobility and movement patterns in a back pain patient group can be compared. Suggestions are offered for the use of EMG biofeedback during dynamic lower back movements as a possible method of alleviating the pain state, perhaps by altering the patient's posture.", "contents": "Normative data on low back mobility and activity levels. Implications for neuromuscular reeducation. Low back mobility and electromyographic movements were performed in 121 normal subjects, grouped by age and sex. Women tended to show greater ranges of motion for straight leg raising, trunk rotation and lateral bending while vertebral separation (forward flexion) was greater in men. A sex-age interaction was observed only in lateral bending, thus implying that for other mobility measurements, data within the age groupings employed in this study can be combined for men and women. Electromyographic data were integrated and quantified using EMG biofeedback equipment for unilateral or bilateral recordings made primarily from the erector spinae muscle between lumbar 3-4 and lumbar 4-5 levels, three centimeters lateral to the spinous processes. Dynamic (trunk flexion-extension, lateral rotation-standing, stooping) and static (quiet sitting, rotation-sitting) movements were performed over a ten second interval. Data analyses verified previous electromyographic studies by demonstrating the trunk extensor function of the erector spinae and the relatively greater unilateral activity when turning to the opposite direction in the erect posture. EMG silence was seen during full trunk flexion. Noticeable sex-age interaction were observed for all dynamic movements but not for static activities. Therefore, it is suggested that EMG data during dynamic movements in a normal population cannot be grouped for men and women within a specified age distribution. These data represent one series of baselines to which mobility and movement patterns in a back pain patient group can be compared. Suggestions are offered for the use of EMG biofeedback during dynamic lower back movements as a possible method of alleviating the pain state, perhaps by altering the patient's posture."} {"id": "PMID:158320", "title": "[A contribution to the experimental procedure for testing anaesthetic drugs in the G\u00f6ttinger minipig (author's transl)].", "content": "An experimental procedure is described for collecting base line data in awake, non-premedicated swine under standard conditions. We implanted catheters into the common carotid artery and in the external jugular vein, which were used either for taking blood samples or for access to the heart for a tip manometer and a flow-directed catheter. One week later we implanted an electromagnetic flow probe at the aortic root. With this preparation, the influence of one, two or several drugs on the heart, blood circulation and respiration can painlessly be demonstrated.", "contents": "[A contribution to the experimental procedure for testing anaesthetic drugs in the G\u00f6ttinger minipig (author's transl)]. An experimental procedure is described for collecting base line data in awake, non-premedicated swine under standard conditions. We implanted catheters into the common carotid artery and in the external jugular vein, which were used either for taking blood samples or for access to the heart for a tip manometer and a flow-directed catheter. One week later we implanted an electromagnetic flow probe at the aortic root. With this preparation, the influence of one, two or several drugs on the heart, blood circulation and respiration can painlessly be demonstrated."} {"id": "PMID:158323", "title": "Activation of nasal cilia in immotile cilia syndrome.", "content": "Nasal biopsy specimens were obtained from 5 normal subjects and from 7 patients with immotile cilia syndrome. Of the latter, 3 had Kartagener's syndrome, one had Kartagener's forme fruste, and 3 had bronchiectasis and sinusitis. An in vitro motility test was used to assess ciliary movement. Exogenous adenosine triphosphate and adenosine triphosphatase activated the immotile cilia to levels equal to or slightly greater than the spontaneous activity seen in normal subjects. Absence of dynein arms on ciliary peripheral microtubule doublets was a consistent finding in the patients' specimens and is suggested to be the basic defect in this syndrome that is responsible for immotility and absence of mucociliary clearance.", "contents": "Activation of nasal cilia in immotile cilia syndrome. Nasal biopsy specimens were obtained from 5 normal subjects and from 7 patients with immotile cilia syndrome. Of the latter, 3 had Kartagener's syndrome, one had Kartagener's forme fruste, and 3 had bronchiectasis and sinusitis. An in vitro motility test was used to assess ciliary movement. Exogenous adenosine triphosphate and adenosine triphosphatase activated the immotile cilia to levels equal to or slightly greater than the spontaneous activity seen in normal subjects. Absence of dynein arms on ciliary peripheral microtubule doublets was a consistent finding in the patients' specimens and is suggested to be the basic defect in this syndrome that is responsible for immotility and absence of mucociliary clearance."} {"id": "PMID:158324", "title": "NIH conference. Systemic lupus erythematosus: evolving concepts.", "content": "Systemic lupus erythematosus, a disease of unknown cause and protean manifestations, continues to excite substantial investigational interest. These papers bring together recent advances in concepts of its immunopathogenesis, evidence for a major genetic role in the causation of the process, developing systems for the morphologic assessment of its often fatal nephritis, and data from ongoing trials of cytotoxic drugs in its management.", "contents": "NIH conference. Systemic lupus erythematosus: evolving concepts. Systemic lupus erythematosus, a disease of unknown cause and protean manifestations, continues to excite substantial investigational interest. These papers bring together recent advances in concepts of its immunopathogenesis, evidence for a major genetic role in the causation of the process, developing systems for the morphologic assessment of its often fatal nephritis, and data from ongoing trials of cytotoxic drugs in its management."} {"id": "PMID:158330", "title": "Pigmentation of osteoma cutis caused by tetracycline.", "content": "Blue nodules developed in the skin of a patient with acne concomitant with the start of tetracycline therapy. When removed, these nodules were brown and histologic examination revealed a lamellate structure compatible with bone. Under ultraviolet light, these osteomas fluoresced yellow, indicating the presence of tetracycline. This suggests that tetracycline, combined with new bone formation, causes pigmentation of osteoma cutis.", "contents": "Pigmentation of osteoma cutis caused by tetracycline. Blue nodules developed in the skin of a patient with acne concomitant with the start of tetracycline therapy. When removed, these nodules were brown and histologic examination revealed a lamellate structure compatible with bone. Under ultraviolet light, these osteomas fluoresced yellow, indicating the presence of tetracycline. This suggests that tetracycline, combined with new bone formation, causes pigmentation of osteoma cutis."} {"id": "PMID:158331", "title": "Long-term effects of interval laparoscopic sterilization by bipolar electrocoagulation on menstruation.", "content": "We studied the menstrual patterns of 258 patients before and after laparoscopic sterilization by bipolar diathermy. The observed changes were obtained were mainly related to the kind of contraception used before sterilization. The frequency of menstrual disorders after sterilization were compared to those in a control group of non-sterilized women matched for age and parity: 12--42 months after the operation, the sterilized women did not have more irregular cycles, menorrhagia, metrorrhagia, hysmenorrhea or dyspareunia than the control group but the sterilized women did have a slightly higher incidence of polymenorrhea (p less than 0.05) and menses lasting less than 3 days (p less than 0.01). We conclude that interval laparoscopic sterilization by bipolar diathermy can be recommended for patients with normal menstrual cycles.", "contents": "Long-term effects of interval laparoscopic sterilization by bipolar electrocoagulation on menstruation. We studied the menstrual patterns of 258 patients before and after laparoscopic sterilization by bipolar diathermy. The observed changes were obtained were mainly related to the kind of contraception used before sterilization. The frequency of menstrual disorders after sterilization were compared to those in a control group of non-sterilized women matched for age and parity: 12--42 months after the operation, the sterilized women did not have more irregular cycles, menorrhagia, metrorrhagia, hysmenorrhea or dyspareunia than the control group but the sterilized women did have a slightly higher incidence of polymenorrhea (p less than 0.05) and menses lasting less than 3 days (p less than 0.01). We conclude that interval laparoscopic sterilization by bipolar diathermy can be recommended for patients with normal menstrual cycles."} {"id": "PMID:158327", "title": "Detection of prethrombotic and thrombotic states.", "content": "Newer methods for detecting subclinical thrombosis are discussed. Uses of radionuclides for thrombus localization are reviewed. Laboratory tests suitable for nonspecialized laboratories are highlighted. The serial use of functional antithrombin III and ethanol gelation assays are recommended to follow the effect of anticoagulant therapy. The use of heparin therapy in low dosage is discussed.", "contents": "Detection of prethrombotic and thrombotic states. Newer methods for detecting subclinical thrombosis are discussed. Uses of radionuclides for thrombus localization are reviewed. Laboratory tests suitable for nonspecialized laboratories are highlighted. The serial use of functional antithrombin III and ethanol gelation assays are recommended to follow the effect of anticoagulant therapy. The use of heparin therapy in low dosage is discussed."} {"id": "PMID:158349", "title": "Improved immunosuppression for cardiac transplantation: immune monitoring and individualized modulation of recipient immunity by in vitro testing.", "content": "These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations.", "contents": "Improved immunosuppression for cardiac transplantation: immune monitoring and individualized modulation of recipient immunity by in vitro testing. These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations."} {"id": "PMID:158350", "title": "[Electrocardiographic evolution of severe medically treated hypertension].", "content": "Electrocardiographic finding were studied in 34 severe hypertensions submitted to antihypertensive therapy. The duration of the survey was between 2 and 6 years. No significant correlation was observed between the changes in pressure and the changes in electrocardiogramm: normalisation of blood pressure could be associated with abnormalities in the electrocardiogramm, concerning especially ST segments and T waves. In the latter case, a high frequency of coronary insufficiency was observed. The results suggested that cardiac factors, independent of the pressure level, could determine the electrocardiographic changes during antihypertensive therapy.", "contents": "[Electrocardiographic evolution of severe medically treated hypertension]. Electrocardiographic finding were studied in 34 severe hypertensions submitted to antihypertensive therapy. The duration of the survey was between 2 and 6 years. No significant correlation was observed between the changes in pressure and the changes in electrocardiogramm: normalisation of blood pressure could be associated with abnormalities in the electrocardiogramm, concerning especially ST segments and T waves. In the latter case, a high frequency of coronary insufficiency was observed. The results suggested that cardiac factors, independent of the pressure level, could determine the electrocardiographic changes during antihypertensive therapy."} {"id": "PMID:158353", "title": "Desmoid tumors and mesenteric fibromatosis in Gardner's syndrome: report of kindred 109.", "content": "Kindred 109, from which Gardner's syndrome was first described, now has 224 members, 28 of whom have inherited the syndrome. Among the group of 28, desmoid tumors or mesenteric fibromatosis or both have developed in eight (29%). In four patients, the fibrous dysplasia appeared to originate in postsurgical abdominal incisional scars; in two of these cases, the mesenteric involvement resulted in death. In one patient, the process was present in the mesentery at the original operation. In three patients, the fibrous dysplastic lesions were extraincisional, with no known trauma associated with their occurrence.", "contents": "Desmoid tumors and mesenteric fibromatosis in Gardner's syndrome: report of kindred 109. Kindred 109, from which Gardner's syndrome was first described, now has 224 members, 28 of whom have inherited the syndrome. Among the group of 28, desmoid tumors or mesenteric fibromatosis or both have developed in eight (29%). In four patients, the fibrous dysplasia appeared to originate in postsurgical abdominal incisional scars; in two of these cases, the mesenteric involvement resulted in death. In one patient, the process was present in the mesentery at the original operation. In three patients, the fibrous dysplastic lesions were extraincisional, with no known trauma associated with their occurrence."} {"id": "PMID:158354", "title": "Experimental allergic uveitis: clinicopathologic features associated with varying doses of S antigen.", "content": "Considerable differences were observed in the experimental autoimmune disease elicited by retinal S antigen, depending on the immunizing dose. An inoculum of 50 microgram produced a massive panophthalmitis containing many polymorphonuclear leukocytes, eosinophils, and mononuclear cells. A less severe endophthalmitis was seen in animals receiving 25 microgram of antigen. Animals receiving between 5 and 10 microgram of antigen developed a disease characterized by a granulomatous uveitis. The inflammatory infiltrate consisted primarily of mononuclear and epithelioid elements and appeared virtually identical to that seen in sympathetic ophthalmia. One microgram of S antigen produced primarily a nongranulomatous posterior uveitis composed chiefly of mononuclear cells. The principal change in the character of the disease occurred at dose levels between 10 and 25 microgram. This change consisted of the disappearance of polymorphonuclear leukocytes and eosinophils at the lower dose levels. These histopathologic changes suggest that at higher dose levels an immune complex disease may be superimposed on or replace a presumably cell-mediated hypersensitivity response.", "contents": "Experimental allergic uveitis: clinicopathologic features associated with varying doses of S antigen. Considerable differences were observed in the experimental autoimmune disease elicited by retinal S antigen, depending on the immunizing dose. An inoculum of 50 microgram produced a massive panophthalmitis containing many polymorphonuclear leukocytes, eosinophils, and mononuclear cells. A less severe endophthalmitis was seen in animals receiving 25 microgram of antigen. Animals receiving between 5 and 10 microgram of antigen developed a disease characterized by a granulomatous uveitis. The inflammatory infiltrate consisted primarily of mononuclear and epithelioid elements and appeared virtually identical to that seen in sympathetic ophthalmia. One microgram of S antigen produced primarily a nongranulomatous posterior uveitis composed chiefly of mononuclear cells. The principal change in the character of the disease occurred at dose levels between 10 and 25 microgram. This change consisted of the disappearance of polymorphonuclear leukocytes and eosinophils at the lower dose levels. These histopathologic changes suggest that at higher dose levels an immune complex disease may be superimposed on or replace a presumably cell-mediated hypersensitivity response."} {"id": "PMID:158357", "title": "The uncA gene codes for the alpha-subunit of the adenosine triphosphatase of Escherichia coli. Electrophoretic analysis of uncA mutant strains.", "content": "Four mutant strains of Escherichia coli which lack membrane-bound adenosine triphosphatase activity were shown by genetic-complementation tests to carry mutations in the uncA gene. A soluble inactive F1-ATPase aggregate was released from the membranes of three of the uncA mutant strains by low-ionic-strength washing, and purified by procedures developed for the purification of F1-ATPase from normal strains. Analysis of the subunit structure by two-dimensional gel electrophoresis indicated that the F1-ATPase in strains carrying the uncA401 or uncA453 alleles had a subunit structure indistinguishable from normal F1-ATPase. In contrast, the F1-ATPase from the strain carrying the uncA447 allele contained an alpha-subunit of normal molecular weight, but abnormal net charge. Membranes from strains carrying the uncA450 allele did not have F1-ATPase aggregates that could be solubilized by low-ionic-strength washing. However, a partial dipolid strain carrying both the uncA+ and uncA450 alleles formed an active F1-ATPase aggregate which could be solubilized by low-ionic-strength washing of the membranes and which contained two types of alpha-subunit, one of which was normal and the other had abnormal net charge. It is concluded that the uncA gene codes for the alpha-subunit of the adenosine triphosphatase.", "contents": "The uncA gene codes for the alpha-subunit of the adenosine triphosphatase of Escherichia coli. Electrophoretic analysis of uncA mutant strains. Four mutant strains of Escherichia coli which lack membrane-bound adenosine triphosphatase activity were shown by genetic-complementation tests to carry mutations in the uncA gene. A soluble inactive F1-ATPase aggregate was released from the membranes of three of the uncA mutant strains by low-ionic-strength washing, and purified by procedures developed for the purification of F1-ATPase from normal strains. Analysis of the subunit structure by two-dimensional gel electrophoresis indicated that the F1-ATPase in strains carrying the uncA401 or uncA453 alleles had a subunit structure indistinguishable from normal F1-ATPase. In contrast, the F1-ATPase from the strain carrying the uncA447 allele contained an alpha-subunit of normal molecular weight, but abnormal net charge. Membranes from strains carrying the uncA450 allele did not have F1-ATPase aggregates that could be solubilized by low-ionic-strength washing. However, a partial dipolid strain carrying both the uncA+ and uncA450 alleles formed an active F1-ATPase aggregate which could be solubilized by low-ionic-strength washing of the membranes and which contained two types of alpha-subunit, one of which was normal and the other had abnormal net charge. It is concluded that the uncA gene codes for the alpha-subunit of the adenosine triphosphatase."} {"id": "PMID:158358", "title": "Properties of membranes from mutant strains of Escherichia coli in which the beta-subunit of the adenosine triphosphatase is abnormal.", "content": "Five uncoupled mutant strains of Escherichia coli carrying mutations in the uncD gene have been studied. In each of these mutant strains the beta-subunit of the F1 portion of the membrane-bound adenosine triphosphatase is abnormal. In one of the mutant strains (carrying the uncD12 allele) in F1-ATPase aggregate was formed which was purified and found to have low ATPase activity. ATPase activity was absent in the other four strains and the abnormal beta-subunits were tightly bound to the membranes. However, membranes from these strains exhibited various proton permeabilities as indicated by NADH-dependent atebrin-fluorescence quenching and bound different amounts of normal F1-ATPase. The amounts of reconstitution of energy-linked reactions after the addition of normal F1-ATPase also varied depending on the mutant allele. It is apparent that considerable phenotypic variations can occur between strains carrying mutations in the same unc gene.", "contents": "Properties of membranes from mutant strains of Escherichia coli in which the beta-subunit of the adenosine triphosphatase is abnormal. Five uncoupled mutant strains of Escherichia coli carrying mutations in the uncD gene have been studied. In each of these mutant strains the beta-subunit of the F1 portion of the membrane-bound adenosine triphosphatase is abnormal. In one of the mutant strains (carrying the uncD12 allele) in F1-ATPase aggregate was formed which was purified and found to have low ATPase activity. ATPase activity was absent in the other four strains and the abnormal beta-subunits were tightly bound to the membranes. However, membranes from these strains exhibited various proton permeabilities as indicated by NADH-dependent atebrin-fluorescence quenching and bound different amounts of normal F1-ATPase. The amounts of reconstitution of energy-linked reactions after the addition of normal F1-ATPase also varied depending on the mutant allele. It is apparent that considerable phenotypic variations can occur between strains carrying mutations in the same unc gene."} {"id": "PMID:158355", "title": "Effect of a single injection of lincomycin, spectinomycin, and linco-spectin on early chick mortality caused by Escherichia coli and Staphylococcus aureus.", "content": "The efficacies of lincomycin (L) and spectinomycin (S), alone and in various combinations (L/S), were determined against Escherichia coli (EC) and Staphylococcus aureus (SA) of avian origin, both in vitro and in vivo. L contributed significantly to L/S activity against SA, while S contributed significantly to L/S activity against EC, and L/S (2.5 mg L + 5.0 mg S) was more effective than either L or S against SA and EC. The suggested optimum dose for controlling early chick mortality caused by SA and EC is 2.5/5.0 mg of L/S per chick.", "contents": "Effect of a single injection of lincomycin, spectinomycin, and linco-spectin on early chick mortality caused by Escherichia coli and Staphylococcus aureus. The efficacies of lincomycin (L) and spectinomycin (S), alone and in various combinations (L/S), were determined against Escherichia coli (EC) and Staphylococcus aureus (SA) of avian origin, both in vitro and in vivo. L contributed significantly to L/S activity against SA, while S contributed significantly to L/S activity against EC, and L/S (2.5 mg L + 5.0 mg S) was more effective than either L or S against SA and EC. The suggested optimum dose for controlling early chick mortality caused by SA and EC is 2.5/5.0 mg of L/S per chick."} {"id": "PMID:158356", "title": "Phage-typing results of Staphylococcus aureus isolated from poultry in Japan and Europe.", "content": "Phage typing was performed on 795 strains of Staphylococcus aureus isolated from poultry, a turkey, pigeons, and birds of prey in Japan and 4 countries in Europe, using the avian phage set of typing phages plus 6 others. Six hundred and seventy-three (89.1%) of 755 strains from poultry were typable by one or more of the phages, 617 strains at routine test dilution (RTD) and 56 strains at 100 RTD. Of these typable strains, 494 (73.4%) belonged to group I, 90 (13.4%) to group II, 50 (7.4%) to group III, 29 (4.3%) to group IV, and 10 (1.5%) to mixed types. There was no significant relation between staphylococcal phage types and the origin of the strains, such as types of disease. Type I strains were commonly found in staphylococci isolated from poultry farms regardless of districts or countries, and thus they were considered to be distributed widely among poultry in Japan and Europe. On the other hand, type III or IV strains were obtained from very limited farms or areas. Four (66.7%) of 6 strains of S. aureus isolated from birds of prey were typed by the additional phage CH39 at RTD. None of 33 pigeon and 1 turkey strain was sensitive to any of the avian phages used.", "contents": "Phage-typing results of Staphylococcus aureus isolated from poultry in Japan and Europe. Phage typing was performed on 795 strains of Staphylococcus aureus isolated from poultry, a turkey, pigeons, and birds of prey in Japan and 4 countries in Europe, using the avian phage set of typing phages plus 6 others. Six hundred and seventy-three (89.1%) of 755 strains from poultry were typable by one or more of the phages, 617 strains at routine test dilution (RTD) and 56 strains at 100 RTD. Of these typable strains, 494 (73.4%) belonged to group I, 90 (13.4%) to group II, 50 (7.4%) to group III, 29 (4.3%) to group IV, and 10 (1.5%) to mixed types. There was no significant relation between staphylococcal phage types and the origin of the strains, such as types of disease. Type I strains were commonly found in staphylococci isolated from poultry farms regardless of districts or countries, and thus they were considered to be distributed widely among poultry in Japan and Europe. On the other hand, type III or IV strains were obtained from very limited farms or areas. Four (66.7%) of 6 strains of S. aureus isolated from birds of prey were typed by the additional phage CH39 at RTD. None of 33 pigeon and 1 turkey strain was sensitive to any of the avian phages used."} {"id": "PMID:158362", "title": "Serum-serum interactions in autoimmune mice.", "content": "Sera from a majority of old, sick mice of the MRL/l strain interact with other MRL/l sera to form visible immunoprecipitates and fix complement. The mouse sera can be divided into two sets such that interset interactions are far more common than intraset ones. The reactive principle in each mouse serum is IgG in the form of an intermediate-sized complex. Reactivity between sera is dependent on IgG anti-IgG specificities.", "contents": "Serum-serum interactions in autoimmune mice. Sera from a majority of old, sick mice of the MRL/l strain interact with other MRL/l sera to form visible immunoprecipitates and fix complement. The mouse sera can be divided into two sets such that interset interactions are far more common than intraset ones. The reactive principle in each mouse serum is IgG in the form of an intermediate-sized complex. Reactivity between sera is dependent on IgG anti-IgG specificities."} {"id": "PMID:158364", "title": "[Influence of local anaesthetics on isolated muscle cells in culture (author's transl)].", "content": "A comparative study was performed on the influence of a series of chemically defined local anaesthetics such as procaine, nicotinoylprocaine and butacaine on isolated skeletal muscle cells and heart cells in culture. About 30 min after addition of local anaesthetics to cell cultures vesicles appear in the cells. These formations are reversible and need a minimum concentration of 13(-3) mol/l procaine, 10(-4) mol/l nicotinoylprocaine, or 10(-4) mol/l butacaine, respectively. Soon after addition of local anaesthetics a reduction of oxygen consumption is measurable in both cell types. The degree of this reduction depends on the chemical structure and the concentration of local anaesthetics and on the kind of cells. After daily addition of local anaesthetics to cell cultures metabolic parameters were studied. The local anaesthetics, except for butacaine, produce an increase of protein concentration, creatine kinase and lactate dehydrogenase activity per sample and an increase of the specific activity of lactate dehydrogenase. These increases depend also on the concentration of local anaesthetics and on the kind of cells. These results support the hypothesis of local anaesthetics action via membrane lipids.", "contents": "[Influence of local anaesthetics on isolated muscle cells in culture (author's transl)]. A comparative study was performed on the influence of a series of chemically defined local anaesthetics such as procaine, nicotinoylprocaine and butacaine on isolated skeletal muscle cells and heart cells in culture. About 30 min after addition of local anaesthetics to cell cultures vesicles appear in the cells. These formations are reversible and need a minimum concentration of 13(-3) mol/l procaine, 10(-4) mol/l nicotinoylprocaine, or 10(-4) mol/l butacaine, respectively. Soon after addition of local anaesthetics a reduction of oxygen consumption is measurable in both cell types. The degree of this reduction depends on the chemical structure and the concentration of local anaesthetics and on the kind of cells. After daily addition of local anaesthetics to cell cultures metabolic parameters were studied. The local anaesthetics, except for butacaine, produce an increase of protein concentration, creatine kinase and lactate dehydrogenase activity per sample and an increase of the specific activity of lactate dehydrogenase. These increases depend also on the concentration of local anaesthetics and on the kind of cells. These results support the hypothesis of local anaesthetics action via membrane lipids."} {"id": "PMID:158365", "title": "[On the effect of methane-bis--phosphonate in vivo (author's transl)].", "content": "After s.c. injections of methane-bis-phosphonate into rabbits, calcified incrustations developed around the injection sites. These incrustations were less radiolucent than the surrounding tissues. They appeared to have a good crystalline apatite structure in X-ray diffraction. The findings agree with our previous in vitro studies but disagree with the findings in the literature that ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethyle-nediphosphonate (Cl2MDP) inhibit crystal growth of apatite already formed.", "contents": "[On the effect of methane-bis--phosphonate in vivo (author's transl)]. After s.c. injections of methane-bis-phosphonate into rabbits, calcified incrustations developed around the injection sites. These incrustations were less radiolucent than the surrounding tissues. They appeared to have a good crystalline apatite structure in X-ray diffraction. The findings agree with our previous in vitro studies but disagree with the findings in the literature that ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethyle-nediphosphonate (Cl2MDP) inhibit crystal growth of apatite already formed."} {"id": "PMID:158377", "title": "Ocular changes in rabbits with corticosteroid-induced ocular hypertension.", "content": "Rabbit eyes with steroid-induced ocular hypertension were investigated in order to evaluate the histochemical abnormalities in the chamber angle region. The right eye of 14 rabbits was treated by dexamethasone 1% 3 times daily for 3 to 5 weeks. The eyes were stained by haematoxylin-eosin, periodic acid Schiff, fibrin, colloidal iron, and alcian blue with and without hyaluronidase. All treated eyes developed elevated intraocular pressure up to 4 weeks after treatment. These globes showed alcian-blue-positive hyaluronidase-sensitive staining in the amorphous material adjacent to Schlemm's canal and in the cytoplasmic granules of trabecular endothelial cells. There was no increase in incorporation of radioactive thymidine into nuclei of endothelial cells as seen by autoradiography. These results provide further support for the idea that there is abnormal accumulation of acid mucopolysaccharides in the chamber angle in steroid-induced ocular hypertension.", "contents": "Ocular changes in rabbits with corticosteroid-induced ocular hypertension. Rabbit eyes with steroid-induced ocular hypertension were investigated in order to evaluate the histochemical abnormalities in the chamber angle region. The right eye of 14 rabbits was treated by dexamethasone 1% 3 times daily for 3 to 5 weeks. The eyes were stained by haematoxylin-eosin, periodic acid Schiff, fibrin, colloidal iron, and alcian blue with and without hyaluronidase. All treated eyes developed elevated intraocular pressure up to 4 weeks after treatment. These globes showed alcian-blue-positive hyaluronidase-sensitive staining in the amorphous material adjacent to Schlemm's canal and in the cytoplasmic granules of trabecular endothelial cells. There was no increase in incorporation of radioactive thymidine into nuclei of endothelial cells as seen by autoradiography. These results provide further support for the idea that there is abnormal accumulation of acid mucopolysaccharides in the chamber angle in steroid-induced ocular hypertension."} {"id": "PMID:158378", "title": "Mechanism of actomyosin adenosine triphosphatase. Evidence that adenosine 5'-triphosphate hydrolysis can occur without dissociation of the actomyosin complex.", "content": "We have investigated the steps in the actomyosin ATPase cycle that determine the maximum ATPase rate (Vmax) and the binding between myosin subfragment one (S-1) and actin which occurs when the ATPase activity is close to Vmax. We find that the forward rate constant of the initial ATP hydrolysis (initial Pi burst) is about 5 times faster than the maximum turnover rate of the actin S-1 ATPase. Thus, another step in the cycle must be considerably slower than the forward rate of the initial Pi burst. If this slower step occurs only when S-1 is complexed with actin, as originally predicted by the Lymn-Taylor model, the ATPase activity and the fraction of S-1 bound to actin in the steady state should increase almost in parallel as the actin concentration is increased. As measured by turbidity determined in the stopped-flow apparatus, the fraction of S-1 bound to actin, like the ATPase activity, shows a hyperbolic dependence on actin concentration, approaching 100% asymptotically. However, the actin concentration required so that 50% of the S-1 is bound to actin is about 4 times greater than the actin concentration required for half-maximal ATPase activity. Thus, as previously found at 0 degrees C, at 15 degrees C much of the S-1 is dissociated from actin when the ATPase is close to Vmax, showing that a slow first-order transition which follows the initial Pi burst (the transition from the refractory to the nonrefractory state) must be the slowest step in the ATPase cycle. Stopped-flow studies also reveal that the steady-state turbidity level is reached almost instantaneously after the S-1, actin, and ATP are mixed, regardless of the order of mixing. Thus, the binding between S-1 and actin which is observed in the steady state is due to a rapid equilibrium between S-1--ATP and acto--S-1--ATP which is shifted toward acto-S-1--ATP at high actin concentration. Furthermore, both S-1--ATP and S-1--ADP.Pi (the state occurring immediately after the initial Pi burst) appear to have the same binding constant to actin. Thus, at high actin concentration both S-1--ATP and S-1--ADP.Pi are in rapid equilibrium with their respective actin complexes. Although at very high actin concentration almost complete binding of S-1--ATP and S-1--ADP.Pi to actin occurs, there is no inhibition of the ATPase activity at high actin concentration. This strongly suggests that both the initial Pi burst and the slow rate-limiting transition which follows (the transition from the refractory to the nonrefractory state) occur at about the same rates whether the S-1 is bound to or dissociated from actin. We, therefore, conclude that S-1 does not have to dissociate from actin each time an ATP molecule is hydrolyzed.", "contents": "Mechanism of actomyosin adenosine triphosphatase. Evidence that adenosine 5'-triphosphate hydrolysis can occur without dissociation of the actomyosin complex. We have investigated the steps in the actomyosin ATPase cycle that determine the maximum ATPase rate (Vmax) and the binding between myosin subfragment one (S-1) and actin which occurs when the ATPase activity is close to Vmax. We find that the forward rate constant of the initial ATP hydrolysis (initial Pi burst) is about 5 times faster than the maximum turnover rate of the actin S-1 ATPase. Thus, another step in the cycle must be considerably slower than the forward rate of the initial Pi burst. If this slower step occurs only when S-1 is complexed with actin, as originally predicted by the Lymn-Taylor model, the ATPase activity and the fraction of S-1 bound to actin in the steady state should increase almost in parallel as the actin concentration is increased. As measured by turbidity determined in the stopped-flow apparatus, the fraction of S-1 bound to actin, like the ATPase activity, shows a hyperbolic dependence on actin concentration, approaching 100% asymptotically. However, the actin concentration required so that 50% of the S-1 is bound to actin is about 4 times greater than the actin concentration required for half-maximal ATPase activity. Thus, as previously found at 0 degrees C, at 15 degrees C much of the S-1 is dissociated from actin when the ATPase is close to Vmax, showing that a slow first-order transition which follows the initial Pi burst (the transition from the refractory to the nonrefractory state) must be the slowest step in the ATPase cycle. Stopped-flow studies also reveal that the steady-state turbidity level is reached almost instantaneously after the S-1, actin, and ATP are mixed, regardless of the order of mixing. Thus, the binding between S-1 and actin which is observed in the steady state is due to a rapid equilibrium between S-1--ATP and acto--S-1--ATP which is shifted toward acto-S-1--ATP at high actin concentration. Furthermore, both S-1--ATP and S-1--ADP.Pi (the state occurring immediately after the initial Pi burst) appear to have the same binding constant to actin. Thus, at high actin concentration both S-1--ATP and S-1--ADP.Pi are in rapid equilibrium with their respective actin complexes. Although at very high actin concentration almost complete binding of S-1--ATP and S-1--ADP.Pi to actin occurs, there is no inhibition of the ATPase activity at high actin concentration. This strongly suggests that both the initial Pi burst and the slow rate-limiting transition which follows (the transition from the refractory to the nonrefractory state) occur at about the same rates whether the S-1 is bound to or dissociated from actin. We, therefore, conclude that S-1 does not have to dissociate from actin each time an ATP molecule is hydrolyzed."} {"id": "PMID:158379", "title": "Magnesium ion dependent adenosine triphosphatase activity of heavy meromyosin as a function of temperature between +20 and -15 degrees C.", "content": "The hydrolysis of Mg2+-adenosine 5'-triphosphate (ATP) by heavy meromyosin has been studied between +20 and -15 degrees C, especially in the low-temperature range, in a medium containing 30% (v/v) ethylene glycol by fluorometric, spectrophotometric, and potentiometric measurements. The time course of the fluorescence changes of the enzyme during the reaction depends markedly on the temperature in consequence of large differences between the activation energies of the various steps. The observed kinetics have been analyzed according to the simplified scheme of Bagshaw & Trentham [Bagshaw, C. R., & Trentham, D. R. (1974) Biochem. J. 141, 331-349]. The following results have been obtained. (1) The rate-limiting step of the reaction changes in this temperature range; at 20 degrees C M**.ADP.Pi is the predominant steady-state complex, and M*.ADP predominates at -15 degrees C, with a half-life of approximately 10 min. (2) As expected, on the basis that it is the dissociation of the M*.ADP complex which becomes rate limiting at low temperature, one observes, in the pre-steady-state below 0 degrees C, both a proton burst and a lag phase in ADP release. (3) At low temperature, the equilibrium M*.ATP in equilibrium M**.ADP.Pi is displaced to the left All the kinetic data obtained in this study are compatible with a simple pathway for the Mg2+-ATP hydrolysis by myosin and with sequential release of the reaction products.", "contents": "Magnesium ion dependent adenosine triphosphatase activity of heavy meromyosin as a function of temperature between +20 and -15 degrees C. The hydrolysis of Mg2+-adenosine 5'-triphosphate (ATP) by heavy meromyosin has been studied between +20 and -15 degrees C, especially in the low-temperature range, in a medium containing 30% (v/v) ethylene glycol by fluorometric, spectrophotometric, and potentiometric measurements. The time course of the fluorescence changes of the enzyme during the reaction depends markedly on the temperature in consequence of large differences between the activation energies of the various steps. The observed kinetics have been analyzed according to the simplified scheme of Bagshaw & Trentham [Bagshaw, C. R., & Trentham, D. R. (1974) Biochem. J. 141, 331-349]. The following results have been obtained. (1) The rate-limiting step of the reaction changes in this temperature range; at 20 degrees C M**.ADP.Pi is the predominant steady-state complex, and M*.ADP predominates at -15 degrees C, with a half-life of approximately 10 min. (2) As expected, on the basis that it is the dissociation of the M*.ADP complex which becomes rate limiting at low temperature, one observes, in the pre-steady-state below 0 degrees C, both a proton burst and a lag phase in ADP release. (3) At low temperature, the equilibrium M*.ATP in equilibrium M**.ADP.Pi is displaced to the left All the kinetic data obtained in this study are compatible with a simple pathway for the Mg2+-ATP hydrolysis by myosin and with sequential release of the reaction products."} {"id": "PMID:158381", "title": "Light-induced Mg2+ ATPase activity of coupling factor in intact chloroplasts.", "content": "Intense illumination isolated, intact, spinach chloroplasts triggers the well known proton-pumping Mg2+ ATPase activity of coupling factor, which can be assayed in subsequently lysed chloroplasts by monitoring ATP-driven quenching of 9-aminoacridine fluorescence. The light-triggered ATPase activity decays slowing in the dark and is inhibited by N,N'-dicyclohexylcarbodiimide. After osmotic lysis and washing of the chloroplasts, preillumination no longer triggers maximal proton-pumping ATPase until methylviologen and dithiothreitol are added to the medium. It is suggested that intact organelles contain soluble or loosely bound cofactors necessary for light-triggering of coupling factor ATPase. On osmotic lysis, these endogenous cofactors are diluted or inactivated and must be replaced by addition of a dithiol reagent and an electron acceptor.", "contents": "Light-induced Mg2+ ATPase activity of coupling factor in intact chloroplasts. Intense illumination isolated, intact, spinach chloroplasts triggers the well known proton-pumping Mg2+ ATPase activity of coupling factor, which can be assayed in subsequently lysed chloroplasts by monitoring ATP-driven quenching of 9-aminoacridine fluorescence. The light-triggered ATPase activity decays slowing in the dark and is inhibited by N,N'-dicyclohexylcarbodiimide. After osmotic lysis and washing of the chloroplasts, preillumination no longer triggers maximal proton-pumping ATPase until methylviologen and dithiothreitol are added to the medium. It is suggested that intact organelles contain soluble or loosely bound cofactors necessary for light-triggering of coupling factor ATPase. On osmotic lysis, these endogenous cofactors are diluted or inactivated and must be replaced by addition of a dithiol reagent and an electron acceptor."} {"id": "PMID:158382", "title": "Correlation between ATP synthesis and the decay of the arotenoid band shift after single flash activation of chromatophores from Rhodopseudomonas capsulata.", "content": "ATP synthesis and the acceleration of the decay of the carotenoid absorption band shift after single flash excitation of Rhodopseudomonas capsulata chromatophores were compared. The two processes behave similarly with respect to: (1) ADP and Pi concentration; (2) inhibition by efrapeptin and venturicidin, and (3) inhibition by valinomycin/K+ and by ionophores. Taken together with earlier evidence for the electrochromic nature of the carotenoid band shift the data support the contention that positive charge moves outwards across the chromatophore membrane during ATP synthesis and justify the method for determination of the H+/ATP ratio (Petty, K.M. and Jackson, J.B. (1979) FEBS Lett. 97, 367-372). The ability of nucleotide diphosphates in the presence of Pi and Mg2+ to give rise to the acceleration of the carotenoid shift decay closely correlates with the rate of phosphorylation of the nucleotides in steady-state light. Nucleotide triphosphates enhance the decay in parallel with their rate of hydrolysis. Adenylyl imidodiphosphate is itself without effect on the decay of the carotenoid shift and it does not prevent the ADP-induced acceleration. The analogue does prevent the ATP effect but only after repeated flashes.", "contents": "Correlation between ATP synthesis and the decay of the arotenoid band shift after single flash activation of chromatophores from Rhodopseudomonas capsulata. ATP synthesis and the acceleration of the decay of the carotenoid absorption band shift after single flash excitation of Rhodopseudomonas capsulata chromatophores were compared. The two processes behave similarly with respect to: (1) ADP and Pi concentration; (2) inhibition by efrapeptin and venturicidin, and (3) inhibition by valinomycin/K+ and by ionophores. Taken together with earlier evidence for the electrochromic nature of the carotenoid band shift the data support the contention that positive charge moves outwards across the chromatophore membrane during ATP synthesis and justify the method for determination of the H+/ATP ratio (Petty, K.M. and Jackson, J.B. (1979) FEBS Lett. 97, 367-372). The ability of nucleotide diphosphates in the presence of Pi and Mg2+ to give rise to the acceleration of the carotenoid shift decay closely correlates with the rate of phosphorylation of the nucleotides in steady-state light. Nucleotide triphosphates enhance the decay in parallel with their rate of hydrolysis. Adenylyl imidodiphosphate is itself without effect on the decay of the carotenoid shift and it does not prevent the ADP-induced acceleration. The analogue does prevent the ATP effect but only after repeated flashes."} {"id": "PMID:158383", "title": "Coupling factor ATPase complex of Rhodospirillum rubrum. Purification and characterization of an oligomycin and N,N'-dicyclohexylcarbodiimide-sensitive (Ca+ + Mg2+)-ATPase.", "content": "An ATPase complex sensitive to the energy transfer inhibitors oligomycin, dicyclohexylcarbodiimide and venturicidin has been solubilized from Rhodospirillum rubrum chromatophores with Triton X-100 and further purified by centrifugation on a glycerol gradient. The partially purified RrFo . F1 contains 13 distinct polypeptide subunits, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, including the subunits of the oligomycin-sensitive, water-soluble RrF1 ATPase. The ATPase activity of RrF0 . F1 as that of the membrane-bound enzyme complex depends on Ca2+ or Mg2+ and from detailed kinetic studies it is concluded that the divalent cation-ATP complex is the substrate for both ATPase complexes. Free ATP and free Mg2+ act as competitive inhibitors, with Ki values of 1 mM and 7 muM, respectively. The subunit composition of the purified RrFo . F1 and its similarity to the membrane-bound ATPase with respect to cation dependence and sensitivity to energy transfer inhibitors suggests that it contains all the subunits of the R. rubrum coupling factor-ATPase complex.", "contents": "Coupling factor ATPase complex of Rhodospirillum rubrum. Purification and characterization of an oligomycin and N,N'-dicyclohexylcarbodiimide-sensitive (Ca+ + Mg2+)-ATPase. An ATPase complex sensitive to the energy transfer inhibitors oligomycin, dicyclohexylcarbodiimide and venturicidin has been solubilized from Rhodospirillum rubrum chromatophores with Triton X-100 and further purified by centrifugation on a glycerol gradient. The partially purified RrFo . F1 contains 13 distinct polypeptide subunits, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, including the subunits of the oligomycin-sensitive, water-soluble RrF1 ATPase. The ATPase activity of RrF0 . F1 as that of the membrane-bound enzyme complex depends on Ca2+ or Mg2+ and from detailed kinetic studies it is concluded that the divalent cation-ATP complex is the substrate for both ATPase complexes. Free ATP and free Mg2+ act as competitive inhibitors, with Ki values of 1 mM and 7 muM, respectively. The subunit composition of the purified RrFo . F1 and its similarity to the membrane-bound ATPase with respect to cation dependence and sensitivity to energy transfer inhibitors suggests that it contains all the subunits of the R. rubrum coupling factor-ATPase complex."} {"id": "PMID:158384", "title": "Localized energization of the mitochondrial inner membrane by ATP.", "content": "Studies were made to determine whether the energy-dependent binding of ethidium to the mitochondrial inner membrane reflects the membrane potential or the energization of localized regions of the membrane. The number of binding sites of ethidium in mitochondria energized with ATP was 72 nmol/mg protein and decreased with increase in the amount of the ATPase system (F1 . F0) inactivated by oligomycin. These findings clearly show that the energy-dependent binding of ethidium to the mitochondrial inner membrane energized with ATP does not reflect the membrane potential, in good accord with the previous conclusion (Higuti, T., Yokota, M., Arakaki, N., Hattori, A. and Tani, I. (1978) Biochim. Biophys. Acta 503, 211-222), but that ethidium binds to localized regions of the energized membrane that are directly affected by ATPase (F1), reflecting the localized energization of the membrane by ATP.", "contents": "Localized energization of the mitochondrial inner membrane by ATP. Studies were made to determine whether the energy-dependent binding of ethidium to the mitochondrial inner membrane reflects the membrane potential or the energization of localized regions of the membrane. The number of binding sites of ethidium in mitochondria energized with ATP was 72 nmol/mg protein and decreased with increase in the amount of the ATPase system (F1 . F0) inactivated by oligomycin. These findings clearly show that the energy-dependent binding of ethidium to the mitochondrial inner membrane energized with ATP does not reflect the membrane potential, in good accord with the previous conclusion (Higuti, T., Yokota, M., Arakaki, N., Hattori, A. and Tani, I. (1978) Biochim. Biophys. Acta 503, 211-222), but that ethidium binds to localized regions of the energized membrane that are directly affected by ATPase (F1), reflecting the localized energization of the membrane by ATP."} {"id": "PMID:158385", "title": "The biogenesis of rat liver mitochondrial ATPase. Subunit composition of the normal ATPase complex and of the deficient complex formed when mitochondrial protein synthesis is blocked.", "content": "1. An ATPase complex containing 12 subunits was isoalted from rat liver mitochondria. 2. In vivo inhibition of mitochondrial protein synthesis by the chloramphenicol analogue thiamphenicol leads to the formation of an oligomycin-insensitive membrane-bound ATPase complex in mitochondria of regenerating rat liver. 3. This oligomycin-insensitive, membrane-bound ATPase was isolated by the same procedure as the ATPase complex from regenerating livers of untreated animals. 4. SDS-polyacrylamide gel electrophoresis of in vivo labelled ATPase complexes from control and from thiamphenicol-treated rats reveals that three subunits out of the 12 are not synthesized or assembled when the mitochondrial translation activity is blocked. 5. From the subunits synthesized and assembled when mitochondrial pror (Fo) of the ATPase complex (subunit 5). 6. The oligomycin sensitivity-conferring protein seems absent in the ATPase complex formed in the presence of thiamphenicol.", "contents": "The biogenesis of rat liver mitochondrial ATPase. Subunit composition of the normal ATPase complex and of the deficient complex formed when mitochondrial protein synthesis is blocked. 1. An ATPase complex containing 12 subunits was isoalted from rat liver mitochondria. 2. In vivo inhibition of mitochondrial protein synthesis by the chloramphenicol analogue thiamphenicol leads to the formation of an oligomycin-insensitive membrane-bound ATPase complex in mitochondria of regenerating rat liver. 3. This oligomycin-insensitive, membrane-bound ATPase was isolated by the same procedure as the ATPase complex from regenerating livers of untreated animals. 4. SDS-polyacrylamide gel electrophoresis of in vivo labelled ATPase complexes from control and from thiamphenicol-treated rats reveals that three subunits out of the 12 are not synthesized or assembled when the mitochondrial translation activity is blocked. 5. From the subunits synthesized and assembled when mitochondrial pror (Fo) of the ATPase complex (subunit 5). 6. The oligomycin sensitivity-conferring protein seems absent in the ATPase complex formed in the presence of thiamphenicol."} {"id": "PMID:158386", "title": "Optimization of the purification of mitochondrial F1-adenosine triphosphatase.", "content": "A simple technique of purification of the soluble pig heart mitochondrial F1-ATPase is described. It consists of removal of extrinsic proteins from mitochondrial membranes before extraction with chloroform and ammonium sulfate fractionation. A high degree of purity, an excellent stability and a good yield are attained after gel filtration through an Ultrogel ACA 34 column equilibrated in the presence of 50% glycerol. The tested properties of the F1-ATPase prepared by this method are similar to those of the same enzyme extracted by sonication. The enzyme is virtually devoid of tightly bound nucleotides. In addition, some characteristics of the behaviour of the beta subunit are shown.", "contents": "Optimization of the purification of mitochondrial F1-adenosine triphosphatase. A simple technique of purification of the soluble pig heart mitochondrial F1-ATPase is described. It consists of removal of extrinsic proteins from mitochondrial membranes before extraction with chloroform and ammonium sulfate fractionation. A high degree of purity, an excellent stability and a good yield are attained after gel filtration through an Ultrogel ACA 34 column equilibrated in the presence of 50% glycerol. The tested properties of the F1-ATPase prepared by this method are similar to those of the same enzyme extracted by sonication. The enzyme is virtually devoid of tightly bound nucleotides. In addition, some characteristics of the behaviour of the beta subunit are shown."} {"id": "PMID:158387", "title": "Localisation of adenine nucleotide-binding sites on beef-heart mitochondrial ATPase by photolabelling with 8-azido-ADP and 8-azido-ATP.", "content": "1. In addition to the previously studied 8-azido-ATP, 8-azido-ADP is a suitable photoaffinity label for beef-heart mitochondrial ATPase (F1). 2. Photolysis at 350 nm of 8-azido-ADP in the presence of isolated F1 leads to inactivation of ATPase activity. Both ATP and ADP (but not AMP) protect against the inactivation. 3. In the absence of Mg2+, 8-azido-ADP binds almost equally to the alpha and beta subunits of F1, whereas in the presence of Mg2+ the alpha subunits are predominantly labelled. 4. The ATPase activity is completely inhibited when two molecules of 8-azido-ADP are bound per molecule F1. 5. 8-Azido-ATP and ATP are competitive substrates for F1, indicating that in the presence of Mg2+ 8-azido-ATP binds to the same site as ATP. 6. The amount of tightly bound nucleotides in F1 is not significantly changed upon incubation with 8-azido-ATP either in the light or the dark. 7. 8-Azido-ATP is also a suitadrial particles, photolabelling leading to inactivation of ATPase activity. 9. Oxidative phosphorylation and the ATP-driven reduction of NAD+ by succinate are also inhibited by photolabelling Mg-ATP particles with 8-azido-ATP. 10. In contrast to the uncoupled ATPase activity, where the two ATP-binding sites do not interact, cooperation between the two sites is required for ATP hydrolysis coupled to reduction of NAD+ by succinate.", "contents": "Localisation of adenine nucleotide-binding sites on beef-heart mitochondrial ATPase by photolabelling with 8-azido-ADP and 8-azido-ATP. 1. In addition to the previously studied 8-azido-ATP, 8-azido-ADP is a suitable photoaffinity label for beef-heart mitochondrial ATPase (F1). 2. Photolysis at 350 nm of 8-azido-ADP in the presence of isolated F1 leads to inactivation of ATPase activity. Both ATP and ADP (but not AMP) protect against the inactivation. 3. In the absence of Mg2+, 8-azido-ADP binds almost equally to the alpha and beta subunits of F1, whereas in the presence of Mg2+ the alpha subunits are predominantly labelled. 4. The ATPase activity is completely inhibited when two molecules of 8-azido-ADP are bound per molecule F1. 5. 8-Azido-ATP and ATP are competitive substrates for F1, indicating that in the presence of Mg2+ 8-azido-ATP binds to the same site as ATP. 6. The amount of tightly bound nucleotides in F1 is not significantly changed upon incubation with 8-azido-ATP either in the light or the dark. 7. 8-Azido-ATP is also a suitadrial particles, photolabelling leading to inactivation of ATPase activity. 9. Oxidative phosphorylation and the ATP-driven reduction of NAD+ by succinate are also inhibited by photolabelling Mg-ATP particles with 8-azido-ATP. 10. In contrast to the uncoupled ATPase activity, where the two ATP-binding sites do not interact, cooperation between the two sites is required for ATP hydrolysis coupled to reduction of NAD+ by succinate."} {"id": "PMID:158388", "title": "The relationship between membrane ATPase activity in sugarcane and heat-induced resistance to helminthosporoside.", "content": "1. Heating of susceptible sugarcane leaves (4 h at 35 degrees C) renders them resistant, for 24 h, to the effects of helminthosporoside. Membrane ATPase activity is reduced by 50% as a result of the heat treatment. When the leaves again become susceptible (after 24 h), membrane. ATPase activity is fully restored. 2. Inhibitors of membrane ATPase activity protect susceptible leaves from the effects of helminthosporoside (KF, EDTA, and octylguanidine). 3. Helminthosporoside activates (30%) membrane ATPase in microsomes from susceptible, but not heat-treated (resistant) leaves. Once heat-treated leaves again become susceptible, helminthosporoside activation of membrane ATPase activity resumes. 4. A plot of the production of helminthosporoside-induced symptoms, and membrane ATPase activity as a function of the reciprocal of the absolute temperature reveals that both have sharp breaks at 32 degrees C. 5. Protoplasts of susceptible cane are rendered insensitivity to the effects of the toxin in a medium deficient in K+ and Mg2+. When these ions are added, cell sensitivity to the toxin is restored. Since K+ uptake in plants is mediated by membrane ATPase, a connection with this enzyme activity can be made to cell sensitivity to the toxin.", "contents": "The relationship between membrane ATPase activity in sugarcane and heat-induced resistance to helminthosporoside. 1. Heating of susceptible sugarcane leaves (4 h at 35 degrees C) renders them resistant, for 24 h, to the effects of helminthosporoside. Membrane ATPase activity is reduced by 50% as a result of the heat treatment. When the leaves again become susceptible (after 24 h), membrane. ATPase activity is fully restored. 2. Inhibitors of membrane ATPase activity protect susceptible leaves from the effects of helminthosporoside (KF, EDTA, and octylguanidine). 3. Helminthosporoside activates (30%) membrane ATPase in microsomes from susceptible, but not heat-treated (resistant) leaves. Once heat-treated leaves again become susceptible, helminthosporoside activation of membrane ATPase activity resumes. 4. A plot of the production of helminthosporoside-induced symptoms, and membrane ATPase activity as a function of the reciprocal of the absolute temperature reveals that both have sharp breaks at 32 degrees C. 5. Protoplasts of susceptible cane are rendered insensitivity to the effects of the toxin in a medium deficient in K+ and Mg2+. When these ions are added, cell sensitivity to the toxin is restored. Since K+ uptake in plants is mediated by membrane ATPase, a connection with this enzyme activity can be made to cell sensitivity to the toxin."} {"id": "PMID:158389", "title": "Mitochondrial DNA from various organisms does not contain internally methylated cytosine in -CCGG- sequences.", "content": "Mitochondrial DNAs from yeast, Neurospora, rat and calf do not contain internally methylated cytosine in -CCGG- sequences.", "contents": "Mitochondrial DNA from various organisms does not contain internally methylated cytosine in -CCGG- sequences. Mitochondrial DNAs from yeast, Neurospora, rat and calf do not contain internally methylated cytosine in -CCGG- sequences."} {"id": "PMID:158390", "title": "Substituent effects on the electron transfer reactivity of hydroquinones with laccase blue copper.", "content": "Stopped-flow kinetic studies of the anaerobic reduction of Rhus vernicifera laccase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) type 1 copper by 25 mono- and disubstituted hydroquinones (H2Q-X) have been performed at 25 degrees C and pH 7.0 in 0.5 M phosphate. All of the data are compatible with a mechanism involving rapid enzyme-substrate complex formation followed by rate-limiting intra-complex electron transfer. ES complex formation constants (Qp) for many substrates are strikingly insensitive to the electronic characteristics of the substituent X, falling within the range 5--50 M-1. It is shown that this result may be accounted for if only the singly ionized forms of the substituted hydroquinones are bound by the enzyme. All of the substrates exhibiting exceptionally high Qp values (greater than 50 M-1) have X groups capable of functioning as ligands; substituents with lone pairs of electrons may facilitate enzyme-substrate complex formation by enabling hydroquinone to function as a bidentate bridging ligand between the type 2 and type 3 copper sites. Intra-complex electron transfer rate constants for most substrates are remarkably insensitive to the thermodynamic driving force for the oxidation of H2Q-X to the corresponding semiquinone, the average value for ten substrates being 30 +/- 10 s-1. The electron transfer reactivity of polyphenols with laccase blue copper therefore appears to be controlled largely by protein-dependent activation requirements rather than by the oxidizability of the substrate.", "contents": "Substituent effects on the electron transfer reactivity of hydroquinones with laccase blue copper. Stopped-flow kinetic studies of the anaerobic reduction of Rhus vernicifera laccase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) type 1 copper by 25 mono- and disubstituted hydroquinones (H2Q-X) have been performed at 25 degrees C and pH 7.0 in 0.5 M phosphate. All of the data are compatible with a mechanism involving rapid enzyme-substrate complex formation followed by rate-limiting intra-complex electron transfer. ES complex formation constants (Qp) for many substrates are strikingly insensitive to the electronic characteristics of the substituent X, falling within the range 5--50 M-1. It is shown that this result may be accounted for if only the singly ionized forms of the substituted hydroquinones are bound by the enzyme. All of the substrates exhibiting exceptionally high Qp values (greater than 50 M-1) have X groups capable of functioning as ligands; substituents with lone pairs of electrons may facilitate enzyme-substrate complex formation by enabling hydroquinone to function as a bidentate bridging ligand between the type 2 and type 3 copper sites. Intra-complex electron transfer rate constants for most substrates are remarkably insensitive to the thermodynamic driving force for the oxidation of H2Q-X to the corresponding semiquinone, the average value for ten substrates being 30 +/- 10 s-1. The electron transfer reactivity of polyphenols with laccase blue copper therefore appears to be controlled largely by protein-dependent activation requirements rather than by the oxidizability of the substrate."} {"id": "PMID:158391", "title": "Transient state kinetic studies of phosphorylation by ATP and Pi of the calcium-dependent ATPase from sarcoplasmic reticulum.", "content": "The ATPase of the sarcoplasmic reticulum is phosphorylated by ATP in the presence of Ca2+. A rapid phosphorylation was observed when the enzyme was preincubated with Ca2+ prior to the addition of 0.1 or 1 mM ATP. The rate of phosphorylation was decreased when Ca2+ was omitted from the preincubation medium and added with ATP when the reaction was started. The rate of phosphorylation by ATP was further decreased when Pi was included in the preincubation medium without Ca2+. In this case, the enzyme was phosphorylated by Pi during the preincubation. When Ca2+ and ATP were added, a burst of phosphorylation by ATP was observed in the initial 16 ms. In the subsequent incubation intervals, the phosphorylation by ATP was synchronous with the hydrolysis of the phosphoenzyme formed by Pi. The rate of hydrolysis of the phosphoenzyme formed by Pi was measured when either the Pi concentration was decreased 10 fold, or when Ca2+, ATP or ATP plus Ca2+ was added to the medium. Upon the single addition of Ca2+, the time for half-maximal decay was in the range 500--1000 ms. In all other conditions it was in the range 70--90 ms.", "contents": "Transient state kinetic studies of phosphorylation by ATP and Pi of the calcium-dependent ATPase from sarcoplasmic reticulum. The ATPase of the sarcoplasmic reticulum is phosphorylated by ATP in the presence of Ca2+. A rapid phosphorylation was observed when the enzyme was preincubated with Ca2+ prior to the addition of 0.1 or 1 mM ATP. The rate of phosphorylation was decreased when Ca2+ was omitted from the preincubation medium and added with ATP when the reaction was started. The rate of phosphorylation by ATP was further decreased when Pi was included in the preincubation medium without Ca2+. In this case, the enzyme was phosphorylated by Pi during the preincubation. When Ca2+ and ATP were added, a burst of phosphorylation by ATP was observed in the initial 16 ms. In the subsequent incubation intervals, the phosphorylation by ATP was synchronous with the hydrolysis of the phosphoenzyme formed by Pi. The rate of hydrolysis of the phosphoenzyme formed by Pi was measured when either the Pi concentration was decreased 10 fold, or when Ca2+, ATP or ATP plus Ca2+ was added to the medium. Upon the single addition of Ca2+, the time for half-maximal decay was in the range 500--1000 ms. In all other conditions it was in the range 70--90 ms."} {"id": "PMID:158392", "title": "Isolation of F-actin filaments. Comparison of F-actin filament preparations from normal and dystrophic mouse muscle.", "content": "To investigate the dystrophic influence on the characteristics of actin, a method for the isolation of F-actin filaments from the skeletal muscle of small sizes, i.e., less than 0.5 g, was devised. In this method, minced muscle was treated with collagenase and hyaluronidase, and the isolated filaments were washed with adenosine triphosphate (ATP). Upon examination in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the ATP-washed filaments showed a protein component identical in mobility to actin in untreated myofibrils or to that prepared by the conventional method. Electron microscopic appearances of the filaments were similar to those of F-actin filaments described in the literature. The dimensions of the filaments were 0.5--2.5 micrometer in length and 60--70 A in diameter. The ability to activate the Mg-adenosine triphosphatase or myosin was found to be Ca2+ independent. In all aspects of the above characteristics, the filaments from leg muscles of 129/Re dydy dystrophic mice and their litter mates were observed to be identical.", "contents": "Isolation of F-actin filaments. Comparison of F-actin filament preparations from normal and dystrophic mouse muscle. To investigate the dystrophic influence on the characteristics of actin, a method for the isolation of F-actin filaments from the skeletal muscle of small sizes, i.e., less than 0.5 g, was devised. In this method, minced muscle was treated with collagenase and hyaluronidase, and the isolated filaments were washed with adenosine triphosphate (ATP). Upon examination in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the ATP-washed filaments showed a protein component identical in mobility to actin in untreated myofibrils or to that prepared by the conventional method. Electron microscopic appearances of the filaments were similar to those of F-actin filaments described in the literature. The dimensions of the filaments were 0.5--2.5 micrometer in length and 60--70 A in diameter. The ability to activate the Mg-adenosine triphosphatase or myosin was found to be Ca2+ independent. In all aspects of the above characteristics, the filaments from leg muscles of 129/Re dydy dystrophic mice and their litter mates were observed to be identical."} {"id": "PMID:158394", "title": "Auxiliary spinal networks for signal focussing in the segmental stretch reflex system.", "content": "In continuation of a previous paper, the auxiliary signal focussing properties of more complicated spinal neuronal networks are considered here. Special emphasis is put on the distributive function of the recurrent feedback system of alpha-motoneurones, but also the inhomogeneous distribution of excitatory and inhibitor input to motoneurones is taken into account as an essential prerequisite for signal focussing. Simple hypothetical calculations for steady-state conditions yield a more vivid insight into the interaction of the two types of neuronal circuitry contributing to signal focussing.", "contents": "Auxiliary spinal networks for signal focussing in the segmental stretch reflex system. In continuation of a previous paper, the auxiliary signal focussing properties of more complicated spinal neuronal networks are considered here. Special emphasis is put on the distributive function of the recurrent feedback system of alpha-motoneurones, but also the inhomogeneous distribution of excitatory and inhibitor input to motoneurones is taken into account as an essential prerequisite for signal focussing. Simple hypothetical calculations for steady-state conditions yield a more vivid insight into the interaction of the two types of neuronal circuitry contributing to signal focussing."} {"id": "PMID:158395", "title": "Decrease of concanavalin-A activated and short lived suppressor T cell function in thyrotoxicosis.", "content": "Function of short lived and concanavalin-A activated suppressor T cells of peripheral blood was studied in patients with thyrotoxicosis and normal individuals. It was found that the activity of short lived and concanavalin-A activated suppressort T cells decreased in untreated patients. Function of concanavalin-A activated suppressor cells relatively increased in euthyroid stage induced by methimazole treatment but failed to reach the normal level. Both the short lived and Concanavalin-A activated suppressor cell activity proved to be in inverse relationships with titres of anti-thyroglobulin antibodies and transformation indices to human thyroglobulin. These findings suggest a possible role of suppressor T cell function in the pathogenesis of Graves' disease.", "contents": "Decrease of concanavalin-A activated and short lived suppressor T cell function in thyrotoxicosis. Function of short lived and concanavalin-A activated suppressor T cells of peripheral blood was studied in patients with thyrotoxicosis and normal individuals. It was found that the activity of short lived and concanavalin-A activated suppressort T cells decreased in untreated patients. Function of concanavalin-A activated suppressor cells relatively increased in euthyroid stage induced by methimazole treatment but failed to reach the normal level. Both the short lived and Concanavalin-A activated suppressor cell activity proved to be in inverse relationships with titres of anti-thyroglobulin antibodies and transformation indices to human thyroglobulin. These findings suggest a possible role of suppressor T cell function in the pathogenesis of Graves' disease."} {"id": "PMID:158396", "title": "Immunosuppressive activity of a purified spleen extract (lymphocytic chalone?) is not due to polyamines spermine and spermidine.", "content": "Spermine, spermidine and a purified spleen extract (PSE) have been compared in vivo in these three tests: hemolytic plaque forming capacity in sensitized mice, delayed hypersensitivity reaction and 3H-thymidine incorporation into various tissue cells. The results obtained demonstrated that the immunosuppressive activity of PSE cannot be attributed to those polyamines. Ion exchange analysis of PSE before and after acid hydrolysis confirmed the absence of free and/or bound polyamines in the studied extract.", "contents": "Immunosuppressive activity of a purified spleen extract (lymphocytic chalone?) is not due to polyamines spermine and spermidine. Spermine, spermidine and a purified spleen extract (PSE) have been compared in vivo in these three tests: hemolytic plaque forming capacity in sensitized mice, delayed hypersensitivity reaction and 3H-thymidine incorporation into various tissue cells. The results obtained demonstrated that the immunosuppressive activity of PSE cannot be attributed to those polyamines. Ion exchange analysis of PSE before and after acid hydrolysis confirmed the absence of free and/or bound polyamines in the studied extract."} {"id": "PMID:158393", "title": "[Immune response dynamics during malignant tumor development].", "content": "Several mathematical models for the development of immune reaction during cancer diseases were plotted. The models describe both stimulation of the immune system by the tumor and its suppression. Non-specific inhibition was considered which resulted from glucose deficiency accompanying the development of a malignant tumor. The inhibiting effect of antitumour antibodies on toxic influence of limphocytes-killers was taken into account. The qualitative and quantitative study of the models showed the limits for the description of real interactions between tumour and organism by the mechanisms stated.", "contents": "[Immune response dynamics during malignant tumor development]. Several mathematical models for the development of immune reaction during cancer diseases were plotted. The models describe both stimulation of the immune system by the tumor and its suppression. Non-specific inhibition was considered which resulted from glucose deficiency accompanying the development of a malignant tumor. The inhibiting effect of antitumour antibodies on toxic influence of limphocytes-killers was taken into account. The qualitative and quantitative study of the models showed the limits for the description of real interactions between tumour and organism by the mechanisms stated."} {"id": "PMID:158397", "title": "Levamisole treatment of inflammatory acne. Restoration of impaired T-cell function accompanied by clearing of the lesions.", "content": "Serum hemolytic complement activity and its components C3, C4 and C1q, serum immunoglobulins A, M and G and peripheral E-rosette forming cells were determined in 11 patients with inflammatory acne. IgG levels were increased and the E-rosette formation was markedly impaired. Levamisole treatment restored the E-rosette formation and improved or cured the inflammatory lesions in 10 out of 11 patients.", "contents": "Levamisole treatment of inflammatory acne. Restoration of impaired T-cell function accompanied by clearing of the lesions. Serum hemolytic complement activity and its components C3, C4 and C1q, serum immunoglobulins A, M and G and peripheral E-rosette forming cells were determined in 11 patients with inflammatory acne. IgG levels were increased and the E-rosette formation was markedly impaired. Levamisole treatment restored the E-rosette formation and improved or cured the inflammatory lesions in 10 out of 11 patients."} {"id": "PMID:158400", "title": "Muscle and serum adenosine triphosphatase in patients suffering from tetanus.", "content": "Serial estimation of muscle and serum adenosine triphosphatase (ATPase) activity was performed in 16 healthy control patients and 32 cases with tetanus. There was no significant difference due to age and sex in muscle and serum ATPase activity between the normal and tetanus cases. Tetanus patients showed a marked increase in muscle and serum ATPase activity as compared to normal. The ATPase activity increased with the severity of convulsion and disease. There was increased mortality in tetanus patients having higher values of muscle and serum ATPase.", "contents": "Muscle and serum adenosine triphosphatase in patients suffering from tetanus. Serial estimation of muscle and serum adenosine triphosphatase (ATPase) activity was performed in 16 healthy control patients and 32 cases with tetanus. There was no significant difference due to age and sex in muscle and serum ATPase activity between the normal and tetanus cases. Tetanus patients showed a marked increase in muscle and serum ATPase activity as compared to normal. The ATPase activity increased with the severity of convulsion and disease. There was increased mortality in tetanus patients having higher values of muscle and serum ATPase."} {"id": "PMID:158401", "title": "The younger disabled unit at Fazakerley Hospital.", "content": "The activities of a new younger disabled unit reflect the changing pattern of care now being provided for severely physically disabled young people. A co-ordinated team approach to their rehabilitation has enabled all but a few of the severely disabled to continue living at home. This represents a considerable saving on the cost of hospital-based care and has afforded them the best opportunity for developing their lives to the full and enjoying a satisfactory life in the community.", "contents": "The younger disabled unit at Fazakerley Hospital. The activities of a new younger disabled unit reflect the changing pattern of care now being provided for severely physically disabled young people. A co-ordinated team approach to their rehabilitation has enabled all but a few of the severely disabled to continue living at home. This represents a considerable saving on the cost of hospital-based care and has afforded them the best opportunity for developing their lives to the full and enjoying a satisfactory life in the community."} {"id": "PMID:158402", "title": "Effects of inflammatory disease on plasma oxprenolol concentrations.", "content": "When single oral doses of oxprenolol were given to three healthy subjects on three separate occasions under standardised conditions the plasma concentration-time curves for each subject were closely similar. In two of the subjects, however, a mild illness led to a dramatic, temporary increase in the peak plasma concentration and area under the plasma concentration-time curve (AUC). This effect of inflammatory disease was confirmed by comparing a group of patients with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour with a group whose ESR was below this value. The mean peak plasma concentration and AUC were significantly higher in the group with a raised ESR. This may be related to altered concentrations of one of the acute-phase proteins. Thus it is concluded that plasma oxprenolol concentrations are raised in inflammatory disease, but further work is needed to determine the mechanism of this increase.", "contents": "Effects of inflammatory disease on plasma oxprenolol concentrations. When single oral doses of oxprenolol were given to three healthy subjects on three separate occasions under standardised conditions the plasma concentration-time curves for each subject were closely similar. In two of the subjects, however, a mild illness led to a dramatic, temporary increase in the peak plasma concentration and area under the plasma concentration-time curve (AUC). This effect of inflammatory disease was confirmed by comparing a group of patients with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour with a group whose ESR was below this value. The mean peak plasma concentration and AUC were significantly higher in the group with a raised ESR. This may be related to altered concentrations of one of the acute-phase proteins. Thus it is concluded that plasma oxprenolol concentrations are raised in inflammatory disease, but further work is needed to determine the mechanism of this increase."} {"id": "PMID:158405", "title": "[Cardiac anti-arrhythmic effect of various N-substituted piperazine derivatives with respect to aconitine in the rat].", "content": "Anti-arrhythmic activity of some piperazine derivatives has been investigated upon cardiac arrythmia induced by aconitine in albinos rat. Among mono-substituted derivatives trimetazidine is active. Among di-substituted derivatives cinepazide and hydroxyzine are active but medibazine have a doubtful activity and piribedil and cinnarizine are devoid of activity.", "contents": "[Cardiac anti-arrhythmic effect of various N-substituted piperazine derivatives with respect to aconitine in the rat]. Anti-arrhythmic activity of some piperazine derivatives has been investigated upon cardiac arrythmia induced by aconitine in albinos rat. Among mono-substituted derivatives trimetazidine is active. Among di-substituted derivatives cinepazide and hydroxyzine are active but medibazine have a doubtful activity and piribedil and cinnarizine are devoid of activity."} {"id": "PMID:158406", "title": "[Effect of adenosine on phosphofructokinase and phosphoglycerate kinase of rat liver].", "content": "Effects of adenosine on purified rat liver phosphofructokinase and phosphoglycerate kinase activity were investigated in vitro. Stimulation by adenosine of the phosphofructokinase has been observed at low concentrations, but the activity was markedly inhibited at high concentrations. Adenosine was an inhibitor of the phosphoglycerate kinase : Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP and non competitive with 3-phosphoglycerate. An interpretation of these results is proposed.", "contents": "[Effect of adenosine on phosphofructokinase and phosphoglycerate kinase of rat liver]. Effects of adenosine on purified rat liver phosphofructokinase and phosphoglycerate kinase activity were investigated in vitro. Stimulation by adenosine of the phosphofructokinase has been observed at low concentrations, but the activity was markedly inhibited at high concentrations. Adenosine was an inhibitor of the phosphoglycerate kinase : Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP and non competitive with 3-phosphoglycerate. An interpretation of these results is proposed."} {"id": "PMID:158407", "title": "[Alterations in concanavalin A binding during retinal development in Xenopus laevis].", "content": "Changes in concanavalin A binding were observed in the retina of Xenopus laevis throughout development. Prior to stage 37, the optic cup and nervous sysetm displayed a light, diffuse staining. Abruptly at stage 37, however, intense staining reaction occurred in the ganglionic fibers, both plexiform layers and photoreceptor inner segments, remaining thus throughout larval and adult life. Our results suggest that important structural modifications occur in retinal cells at the time of establishment of connections with the tectum, preceedings, and possibility related to, electrical functioning of the visual system.", "contents": "[Alterations in concanavalin A binding during retinal development in Xenopus laevis]. Changes in concanavalin A binding were observed in the retina of Xenopus laevis throughout development. Prior to stage 37, the optic cup and nervous sysetm displayed a light, diffuse staining. Abruptly at stage 37, however, intense staining reaction occurred in the ganglionic fibers, both plexiform layers and photoreceptor inner segments, remaining thus throughout larval and adult life. Our results suggest that important structural modifications occur in retinal cells at the time of establishment of connections with the tectum, preceedings, and possibility related to, electrical functioning of the visual system."} {"id": "PMID:158408", "title": "[New data on serotoninergic mechanisms in ovulation in the cyclic female rat].", "content": "Injection of parachlorophenylalanine on dioestrus II at 18:00 was shown to decrease ovulation frequency in 4-day cyclic female rats. This effect was overcome by either HTP, or oestradiol benzoate, when administered on dioestrus II, at 18:00 and 10:00 - 11:00 respectively. No antiovulatory action of PCPA was observed on prooestrus at 13:00. These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control.", "contents": "[New data on serotoninergic mechanisms in ovulation in the cyclic female rat]. Injection of parachlorophenylalanine on dioestrus II at 18:00 was shown to decrease ovulation frequency in 4-day cyclic female rats. This effect was overcome by either HTP, or oestradiol benzoate, when administered on dioestrus II, at 18:00 and 10:00 - 11:00 respectively. No antiovulatory action of PCPA was observed on prooestrus at 13:00. These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control."} {"id": "PMID:158409", "title": "[Effect of testosterone or progesterone implants on the intensity of experimental infestation with Schistosoma mansoni in the female golden hamster].", "content": "When administered in pellet form of 20 mg to castrated Golden female hamsters, testosterone leads to a decrease of the intensity of experimental infestation with Schistosoma mansoni. The same result is obtained when estradiol is used in place of testosterone under the same conditions. On the contrary, no statiscally significant decrease has been observed with progesterone.", "contents": "[Effect of testosterone or progesterone implants on the intensity of experimental infestation with Schistosoma mansoni in the female golden hamster]. When administered in pellet form of 20 mg to castrated Golden female hamsters, testosterone leads to a decrease of the intensity of experimental infestation with Schistosoma mansoni. The same result is obtained when estradiol is used in place of testosterone under the same conditions. On the contrary, no statiscally significant decrease has been observed with progesterone."} {"id": "PMID:158410", "title": "[Combination of chemotherapy and radiotherapy. I. Differential effect on the intestinal syndrome of irradiation combined with the drug administered in fractional doses and at various times].", "content": "We have studied the different effects on the intestinal syndrome between the administration of fractional doses of 5-Fu before and after irradiation. There is no difference between the diverse modalities and we obtain the same result when the 5-Fu is administered, fractionated or not, before or after the irradiation.", "contents": "[Combination of chemotherapy and radiotherapy. I. Differential effect on the intestinal syndrome of irradiation combined with the drug administered in fractional doses and at various times]. We have studied the different effects on the intestinal syndrome between the administration of fractional doses of 5-Fu before and after irradiation. There is no difference between the diverse modalities and we obtain the same result when the 5-Fu is administered, fractionated or not, before or after the irradiation."} {"id": "PMID:158411", "title": "[Combination of chemotherapy and radiotherapy. II. Differential effect on the medullary syndrome of irradiation combined with the drug administered in fractional doses and at various times].", "content": "We have studied the effect of 5-Fu in fractional doses on the medullar syndrome after a single whole body cobalt irradiation in mice. The bone marrow is not sensitive to the fractionation of 5-Fu and it is the single dose of 5-Fu injected 72 hours after the irradiation which is the most effective.", "contents": "[Combination of chemotherapy and radiotherapy. II. Differential effect on the medullary syndrome of irradiation combined with the drug administered in fractional doses and at various times]. We have studied the effect of 5-Fu in fractional doses on the medullar syndrome after a single whole body cobalt irradiation in mice. The bone marrow is not sensitive to the fractionation of 5-Fu and it is the single dose of 5-Fu injected 72 hours after the irradiation which is the most effective."} {"id": "PMID:158412", "title": "[Interstitial transudation with postural changes in man].", "content": "Starling-Landis concepts of formation of interstitial fluids are in agreement with measurements of calf volume in normal young women, in horizontal recumbency or after horizontal immersion. The volume of the calf is reduced when the hydrostatic pressure of the blood column is diminished under the phlebostatic level and when the external pressure is increased by the hydrostatic pressure of the water bath.", "contents": "[Interstitial transudation with postural changes in man]. Starling-Landis concepts of formation of interstitial fluids are in agreement with measurements of calf volume in normal young women, in horizontal recumbency or after horizontal immersion. The volume of the calf is reduced when the hydrostatic pressure of the blood column is diminished under the phlebostatic level and when the external pressure is increased by the hydrostatic pressure of the water bath."} {"id": "PMID:158413", "title": "[Various aspects of lipid metabolism in the rat testicle after sulpiride treatment].", "content": "Testicular lipids were extracted from 20 rats which had received 40 mg sulpiride per kg per day for 20 days as well as from 20 controls. The extracts were weighed and chromatographed on thin layer in order to analyse them for the main fatty constituants : phospholipids and neutral fats. In addition total cholesterol, triglycerides and lipid phosphorus were determined. The total testicular lipid content and the phospholipids were unaltered. The distribution of phospholipids wasn't influenced either. Among the neutral fats the precursors of steroid hormones such as cholesterol and its esters didn't show any modification. The triglycerides on the other hand suffered a significant decrease which was partly compensated in situ by the increase of free fatty acids. Since plasma electrophoresis didn't reveal a parallel increase of the complex albumin--free fatty acids, the hypothesis of an in situ lipolysis is proposed. But it is not possible yet to attribute to sulpiride the role of a direct activation on a testicular triglyceride lipase nor that of an indirect activator by way of prolactine for example.", "contents": "[Various aspects of lipid metabolism in the rat testicle after sulpiride treatment]. Testicular lipids were extracted from 20 rats which had received 40 mg sulpiride per kg per day for 20 days as well as from 20 controls. The extracts were weighed and chromatographed on thin layer in order to analyse them for the main fatty constituants : phospholipids and neutral fats. In addition total cholesterol, triglycerides and lipid phosphorus were determined. The total testicular lipid content and the phospholipids were unaltered. The distribution of phospholipids wasn't influenced either. Among the neutral fats the precursors of steroid hormones such as cholesterol and its esters didn't show any modification. The triglycerides on the other hand suffered a significant decrease which was partly compensated in situ by the increase of free fatty acids. Since plasma electrophoresis didn't reveal a parallel increase of the complex albumin--free fatty acids, the hypothesis of an in situ lipolysis is proposed. But it is not possible yet to attribute to sulpiride the role of a direct activation on a testicular triglyceride lipase nor that of an indirect activator by way of prolactine for example."} {"id": "PMID:158414", "title": "[Effects of the virus-inhibiting factor or interferon on the in vitro multiplication of mouse tumor cells].", "content": "1) The in vitro effect of virus-inhibiting factor (IF) or interferon on Ehrlich ascites tumor and sarcoma 180 was found to be cytostatic, but not cytocidal. 2) Mouse peritoneal macrophages or splenic lymphoid cells, in the presence of IF, did not affect multiplication of the tumor cells examined.", "contents": "[Effects of the virus-inhibiting factor or interferon on the in vitro multiplication of mouse tumor cells]. 1) The in vitro effect of virus-inhibiting factor (IF) or interferon on Ehrlich ascites tumor and sarcoma 180 was found to be cytostatic, but not cytocidal. 2) Mouse peritoneal macrophages or splenic lymphoid cells, in the presence of IF, did not affect multiplication of the tumor cells examined."} {"id": "PMID:158415", "title": "[Comparative ultrastructural study of the inhibiting effect of deoxyguanosine and of caffeine on Allium sativum L. cytokinetics].", "content": "These two inhibitors of cytokinesis have two different modes of action, the first one acting during G2 and the second during M. This study underlines the action of caffeine on the fusion of cytokinesis vesicles. On the other hand, the cell vacuolization induced by deoxyguanosine is not directly relevant to the stathmodieretic action.", "contents": "[Comparative ultrastructural study of the inhibiting effect of deoxyguanosine and of caffeine on Allium sativum L. cytokinetics]. These two inhibitors of cytokinesis have two different modes of action, the first one acting during G2 and the second during M. This study underlines the action of caffeine on the fusion of cytokinesis vesicles. On the other hand, the cell vacuolization induced by deoxyguanosine is not directly relevant to the stathmodieretic action."} {"id": "PMID:158416", "title": "[Activities evoked in different strain structures by stimulation of the contralateral tectum in the chick].", "content": "In the chick, as soon as hatching, the responses recorded in various areas in the \"accessorius hyperstriatum\" (Wulst) seem to be very localized in relation with the stimulated region of the contralateral tectum. Very similar results are obtained within the other striate structures. These observations suggest in first part, that the tectal efferents project very diffusely to various striate structures and, in other part, that it exists in these a rather precise tectotopy and a columnar organisation. These results appear very constant during the first month of the hatching.", "contents": "[Activities evoked in different strain structures by stimulation of the contralateral tectum in the chick]. In the chick, as soon as hatching, the responses recorded in various areas in the \"accessorius hyperstriatum\" (Wulst) seem to be very localized in relation with the stimulated region of the contralateral tectum. Very similar results are obtained within the other striate structures. These observations suggest in first part, that the tectal efferents project very diffusely to various striate structures and, in other part, that it exists in these a rather precise tectotopy and a columnar organisation. These results appear very constant during the first month of the hatching."} {"id": "PMID:158417", "title": "[Uptake and esterification of (4-14C) cholesterol after injection into the cerebral ventricles of conscious cats].", "content": "The brain tissue had appreciable capacity to take up and to esterify (4-14C) cholesterol from the cats cerebral ventricles. The highest values of radioactive material in the brain tissue were found 30 minutes after intraventricular injection of (4-14C) cholesterol. Thereafter, within a few hours most of the labelled cholesterol disappeared and by the end of 48 h the brain tissue retained only small amounts of it. at the same time, radioactive material was found in the peripheral venous blood, but in very small amounts. The analysis for cholesterol esters showed that about 50 % of (4-14C) cholesterol taken up by the brain tissue had undergone esterification. The rate of esterification of cholesterol within 48 h remained more or less constant, although a significant peak was noted by the end of 24 h.", "contents": "[Uptake and esterification of (4-14C) cholesterol after injection into the cerebral ventricles of conscious cats]. The brain tissue had appreciable capacity to take up and to esterify (4-14C) cholesterol from the cats cerebral ventricles. The highest values of radioactive material in the brain tissue were found 30 minutes after intraventricular injection of (4-14C) cholesterol. Thereafter, within a few hours most of the labelled cholesterol disappeared and by the end of 48 h the brain tissue retained only small amounts of it. at the same time, radioactive material was found in the peripheral venous blood, but in very small amounts. The analysis for cholesterol esters showed that about 50 % of (4-14C) cholesterol taken up by the brain tissue had undergone esterification. The rate of esterification of cholesterol within 48 h remained more or less constant, although a significant peak was noted by the end of 24 h."} {"id": "PMID:158418", "title": "[Cytotoxic action of Pseudomonas aeruginosa hemolysin].", "content": "The cytopathic action of haemolysin of Pseudomonas aeruginosa has been studied in mouse and human leucocytes. The morphological changes suggest that haemolysin affects the molecular architecture of the cell membrane, whose permeability is increased. It does not induce non-specific stimulation of peripheral lymphocytes. Normal sera and albumin neutralize the hemolytic activity of haemolysin; this inhibition is also observed, to a les extent, on the lytic action on leucocytes. This raises the possibility that the two activities are probably associated with the same molecule.", "contents": "[Cytotoxic action of Pseudomonas aeruginosa hemolysin]. The cytopathic action of haemolysin of Pseudomonas aeruginosa has been studied in mouse and human leucocytes. The morphological changes suggest that haemolysin affects the molecular architecture of the cell membrane, whose permeability is increased. It does not induce non-specific stimulation of peripheral lymphocytes. Normal sera and albumin neutralize the hemolytic activity of haemolysin; this inhibition is also observed, to a les extent, on the lytic action on leucocytes. This raises the possibility that the two activities are probably associated with the same molecule."} {"id": "PMID:158419", "title": "[Ultrastructural study of the different zones of the rat liver acinus after portacaval anastomosis].", "content": "Liver atrophy is a main feature in rats with a porto caval shunt. Histological studies revealed small size hepatocytes. Ultrastructural differences between periportal and centrolobular zones were noticed, in particular, the dilatation of the nuclear envelope and of the rough endoplasmic reticulum which appeared dilated, desorganized and sometimes without ribosomes, was more pronounced in the periportal zone. Hepatocytes of this zone might be more sensitive to the decrease of O2 and/or hepatotrophic factors.", "contents": "[Ultrastructural study of the different zones of the rat liver acinus after portacaval anastomosis]. Liver atrophy is a main feature in rats with a porto caval shunt. Histological studies revealed small size hepatocytes. Ultrastructural differences between periportal and centrolobular zones were noticed, in particular, the dilatation of the nuclear envelope and of the rough endoplasmic reticulum which appeared dilated, desorganized and sometimes without ribosomes, was more pronounced in the periportal zone. Hepatocytes of this zone might be more sensitive to the decrease of O2 and/or hepatotrophic factors."} {"id": "PMID:158420", "title": "[Chemical study on acetabular cartilage adjoining a prosthetic implant: experimental study in the rabbit].", "content": "The authors present an experimental study of the rabbit femoral prosthesis compatibility : macroscopical aspect, proteoglycan content and metabolism of the acetabular cartilage.", "contents": "[Chemical study on acetabular cartilage adjoining a prosthetic implant: experimental study in the rabbit]. The authors present an experimental study of the rabbit femoral prosthesis compatibility : macroscopical aspect, proteoglycan content and metabolism of the acetabular cartilage."} {"id": "PMID:158421", "title": "[Vasomotor innervation of the maxillary canines of the dog].", "content": "Maxillary canine pulpar pressure was recorded on anesthetized dogs by means of a small bore cannula threaded into a hole drilled through the lateral surface of the tooth. Vasoconstriction was brought by the electrical stimulation of the cranial cervical ganglion. Vasodilation was induced by stilmulation of the pterygo-palatine ganglion. This vasodilation was inhibited by atropine. Most often, constrictor fibres follow the course of the pterygo-palatine nerve, when dilator fibres follow the infraorbital nerve. However, both sorts of fibres may be found in the infraorbital nerve.", "contents": "[Vasomotor innervation of the maxillary canines of the dog]. Maxillary canine pulpar pressure was recorded on anesthetized dogs by means of a small bore cannula threaded into a hole drilled through the lateral surface of the tooth. Vasoconstriction was brought by the electrical stimulation of the cranial cervical ganglion. Vasodilation was induced by stilmulation of the pterygo-palatine ganglion. This vasodilation was inhibited by atropine. Most often, constrictor fibres follow the course of the pterygo-palatine nerve, when dilator fibres follow the infraorbital nerve. However, both sorts of fibres may be found in the infraorbital nerve."} {"id": "PMID:158422", "title": "[Effect of anti-inflammatory agent administration on Balb/c mouse peritoneal macrophage activity].", "content": "A study of the mouse Balb/c peritoneal macrophages has been made after oral antiinflammatory drugs administration on animals which previously had an inflammation with carrageenan. The results show an enhancement of the number of the macrophages, of their enzymatic activities and of their proteins' content. These three parameters fall down more or less rapidly according to the considered antiinflammatory drug.", "contents": "[Effect of anti-inflammatory agent administration on Balb/c mouse peritoneal macrophage activity]. A study of the mouse Balb/c peritoneal macrophages has been made after oral antiinflammatory drugs administration on animals which previously had an inflammation with carrageenan. The results show an enhancement of the number of the macrophages, of their enzymatic activities and of their proteins' content. These three parameters fall down more or less rapidly according to the considered antiinflammatory drug."} {"id": "PMID:158423", "title": "[Nidation in the Triton W.R. 1339 treated mouse: effect of progesterone and estradiol].", "content": "In the mouse injection of 800 mg/kg of Triton W.R. 1339 during the first four days of gestation prevents nidation. Examination of the uterine horns between days 6-12 reveals that a daily injection of 5 mg progesterone up from day 1 of gestation assures the survival of the blastocysts in Triton W.R. 1339 treated females and determines a delayed nidation. Nidations occur only after injection of 0.1 microgram of oestradiol benzoate at the beginning of the 5th day.", "contents": "[Nidation in the Triton W.R. 1339 treated mouse: effect of progesterone and estradiol]. In the mouse injection of 800 mg/kg of Triton W.R. 1339 during the first four days of gestation prevents nidation. Examination of the uterine horns between days 6-12 reveals that a daily injection of 5 mg progesterone up from day 1 of gestation assures the survival of the blastocysts in Triton W.R. 1339 treated females and determines a delayed nidation. Nidations occur only after injection of 0.1 microgram of oestradiol benzoate at the beginning of the 5th day."} {"id": "PMID:158425", "title": "Separation of odontoblast Ca2+-ATPase and alkaline phosphatase.", "content": "Ca2+-ATPase activity was solubilized, partly purified, and separated from nonspecific alkaline phosphatase activity (APase1) of dentinogenically active rat incisor odontoblasts. Attempts were made to extract the enzymes by various agents, such as Triton X-100, deoxycholate, butanol, EDTA, and buffers of decreasing ionic strength. Solubilization by butanol followed by extraction with low concentrations of EDTA proved to be most effective. Purification and separation were done by molecular sieve chromatography. Ca2+-ATPase showed no activity against p-nitrophenyl phosphate (p-NPP) or inorganic pyrophosphate (PPi) and was unaffected by R 8231 [+/-)-6(m-bromophenyl)-5,6-dihydroimidazo(2,1-b)thiazole oxalate]. It was activated by Ca2+ and Mg2+ ions in equimolar concentrations with the substrate. The enzyme was rapidly inactivated in the solubilized state. An apparent molecular weight of about 18,000 was obtained from molecular sieve data. APase, showing activity against ATP, PPi, and p-NPP, was virtually totally inhibited by R 8231. It was activated by Mg2+ ions but slightly reduced in activity by Ca2+ ions. It had an apparent mol. wt. of 79,000. The results provide direct evidence for earlier suggestions of the existence in hard tissue forming cells of two phosphatases active at alkaline pH.", "contents": "Separation of odontoblast Ca2+-ATPase and alkaline phosphatase. Ca2+-ATPase activity was solubilized, partly purified, and separated from nonspecific alkaline phosphatase activity (APase1) of dentinogenically active rat incisor odontoblasts. Attempts were made to extract the enzymes by various agents, such as Triton X-100, deoxycholate, butanol, EDTA, and buffers of decreasing ionic strength. Solubilization by butanol followed by extraction with low concentrations of EDTA proved to be most effective. Purification and separation were done by molecular sieve chromatography. Ca2+-ATPase showed no activity against p-nitrophenyl phosphate (p-NPP) or inorganic pyrophosphate (PPi) and was unaffected by R 8231 [+/-)-6(m-bromophenyl)-5,6-dihydroimidazo(2,1-b)thiazole oxalate]. It was activated by Ca2+ and Mg2+ ions in equimolar concentrations with the substrate. The enzyme was rapidly inactivated in the solubilized state. An apparent molecular weight of about 18,000 was obtained from molecular sieve data. APase, showing activity against ATP, PPi, and p-NPP, was virtually totally inhibited by R 8231. It was activated by Mg2+ ions but slightly reduced in activity by Ca2+ ions. It had an apparent mol. wt. of 79,000. The results provide direct evidence for earlier suggestions of the existence in hard tissue forming cells of two phosphatases active at alkaline pH."} {"id": "PMID:158426", "title": "Transduction of penicillinase production in Staphylococcus epidermidis and nature of the genetic determinant.", "content": "Four strains of Staphylococcus epidermidis from clinical sources were capable of serving as donors for the transduction of either penicillinase production, ethidium bromide resistance, or tetracycline resistance. Three typing phages served as transducing phages and, depending upon the combination of transducing phage, donor strain, and recipient strain, the rates of transduction ranged between 10(-5) and 10(-9). In one strain, cotransduction of penicillinase production and ethidium bromide resistance was observed. Although ultraviolet irradiation kinetics indicated that both the tetracycline resistance and the penicillin resistance determinants were located on plasmids, only resistance to tetracycline could be eliminated by growth in the presence of curing agents or at elevated temperature. However, evidence was obtained by agarose gel electrophoretic studies that both the tetracycline resistance and the penicillin resistance determinants are located on separate plasmids in this organism.", "contents": "Transduction of penicillinase production in Staphylococcus epidermidis and nature of the genetic determinant. Four strains of Staphylococcus epidermidis from clinical sources were capable of serving as donors for the transduction of either penicillinase production, ethidium bromide resistance, or tetracycline resistance. Three typing phages served as transducing phages and, depending upon the combination of transducing phage, donor strain, and recipient strain, the rates of transduction ranged between 10(-5) and 10(-9). In one strain, cotransduction of penicillinase production and ethidium bromide resistance was observed. Although ultraviolet irradiation kinetics indicated that both the tetracycline resistance and the penicillin resistance determinants were located on plasmids, only resistance to tetracycline could be eliminated by growth in the presence of curing agents or at elevated temperature. However, evidence was obtained by agarose gel electrophoretic studies that both the tetracycline resistance and the penicillin resistance determinants are located on separate plasmids in this organism."} {"id": "PMID:158428", "title": "Isolation of the chicken beta-globin gene and a linked embryonic beta-like globin gene from a chicken DNA recombinant library.", "content": "A library of random chicken DNA fragments, 15-22 kb long, has been prepared in the vector lambda Charon 4A. This library was screened with combined adult and embryonic globin cDNA, and several independent globin gene-containing recombinants were isolated. One of these recombinants, lambda Chicken beta-globin 1 (lambda C beta G1), contains the adult chicken beta-globin gene and a closely linked embryonic beta-like globin gene. Both genes are transcribed in the same direction with the adult gene located 5' to the embryonic gene. Electron microscopic visualization of R loop structures generated by hybridization of globin RNA to lambda C beta G1 demonstrates that both globin genes contain major intervening sequences about 800 bp long, similar to those present in mammalian beta-globin genes. The adult beta-globin gene also contains a minor (approximately 100 bp long) intervening sequence analogous to the one observed in mammalian beta-globin genes. Restriction enzyme analysis of the adult beta-globin gene on lambda C beta G1 is consistent with the hypothesis that its two intervening sequences occur in the same positions with respect to the beta-globin amino acid sequence as do the corresponding mammalian intervening sequences.", "contents": "Isolation of the chicken beta-globin gene and a linked embryonic beta-like globin gene from a chicken DNA recombinant library. A library of random chicken DNA fragments, 15-22 kb long, has been prepared in the vector lambda Charon 4A. This library was screened with combined adult and embryonic globin cDNA, and several independent globin gene-containing recombinants were isolated. One of these recombinants, lambda Chicken beta-globin 1 (lambda C beta G1), contains the adult chicken beta-globin gene and a closely linked embryonic beta-like globin gene. Both genes are transcribed in the same direction with the adult gene located 5' to the embryonic gene. Electron microscopic visualization of R loop structures generated by hybridization of globin RNA to lambda C beta G1 demonstrates that both globin genes contain major intervening sequences about 800 bp long, similar to those present in mammalian beta-globin genes. The adult beta-globin gene also contains a minor (approximately 100 bp long) intervening sequence analogous to the one observed in mammalian beta-globin genes. Restriction enzyme analysis of the adult beta-globin gene on lambda C beta G1 is consistent with the hypothesis that its two intervening sequences occur in the same positions with respect to the beta-globin amino acid sequence as do the corresponding mammalian intervening sequences."} {"id": "PMID:158442", "title": "[Cloning of the hepatitis B virus genome in Escherichia coli].", "content": "The whole genome of the hepatitis B virus (Dane particles) was inserted in vitro in the genome of the bacteriophage lambda gtWES . LAMBDA B. The recombinant DNA molecule was cloned in E. coli. Amplification of the hybrid bacteriophage enables the preparation of large amounts of hepatitis B virus DNA. The possibilities offered by the utilization of this recombinant bacteriophage are discussed.", "contents": "[Cloning of the hepatitis B virus genome in Escherichia coli]. The whole genome of the hepatitis B virus (Dane particles) was inserted in vitro in the genome of the bacteriophage lambda gtWES . LAMBDA B. The recombinant DNA molecule was cloned in E. coli. Amplification of the hybrid bacteriophage enables the preparation of large amounts of hepatitis B virus DNA. The possibilities offered by the utilization of this recombinant bacteriophage are discussed."} {"id": "PMID:158445", "title": "Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study.", "content": "Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and may also occur in normal subjects. A ratio greater than or equal to 1.5 may be more specific for genetically determined asymmetric septal hypertrophy.", "contents": "Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study. Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and may also occur in normal subjects. A ratio greater than or equal to 1.5 may be more specific for genetically determined asymmetric septal hypertrophy."} {"id": "PMID:158446", "title": "Adenylate cyclase and ATPase activities in red cell membranes of patients and genetic carriers of Duchenne muscular dystrophy.", "content": "Basal adenylate cyclase activity was increased in red cell ghosts from both patients with Duchenne muscular dystrophy and their mothers when the activities were compared to proper age-matched controls. The activity of ATPase measured in the presence of Na+, K+, and Mg2+ was not found to be different in erythrocyte ghosts from Duchenne dystrophic patients, age-matched controls, or the mothers of Duchenne patients, and ouabain inhibited ATPase in ghosts to the same extent in all membrane preparations.", "contents": "Adenylate cyclase and ATPase activities in red cell membranes of patients and genetic carriers of Duchenne muscular dystrophy. Basal adenylate cyclase activity was increased in red cell ghosts from both patients with Duchenne muscular dystrophy and their mothers when the activities were compared to proper age-matched controls. The activity of ATPase measured in the presence of Na+, K+, and Mg2+ was not found to be different in erythrocyte ghosts from Duchenne dystrophic patients, age-matched controls, or the mothers of Duchenne patients, and ouabain inhibited ATPase in ghosts to the same extent in all membrane preparations."} {"id": "PMID:158444", "title": "Psychological factors in feeding disorders occurring in mentally or multiply handicapped children.", "content": "This is a discussion of the psychological aspects of non-organic feeding problems occurring in infancy and early childhood. There are particular difficulties caused by parental responses to a handicapped child and these increase the likelihood of feeding problems. The temperament and personality of the child can pose additional problems. Early counselling for families of handicapped babies can facilitate normal mourning and the mobilization of practical help, and reduce the incidence of non-organic feeding problems.", "contents": "Psychological factors in feeding disorders occurring in mentally or multiply handicapped children. This is a discussion of the psychological aspects of non-organic feeding problems occurring in infancy and early childhood. There are particular difficulties caused by parental responses to a handicapped child and these increase the likelihood of feeding problems. The temperament and personality of the child can pose additional problems. Early counselling for families of handicapped babies can facilitate normal mourning and the mobilization of practical help, and reduce the incidence of non-organic feeding problems."} {"id": "PMID:158447", "title": "A chromosome survey of a hospital for the mentally subnormal.", "content": "A cytogenetic survey of 756 resident, but otherwise unselected, mentally retarded patients in a Scottish hospital is reported. The karyotypes of all patients were examined using orcein-stained cells, and those found to be abnormal, other than those with standard trisomy 21, were further investigated using a banding technique. A total of 103 patients were found to have an abnormal chromosome complement, of whom 91 had Down's syndrome (including six with translocations), six had some other autosomal abnormality, and six had an abnormality of the sex chromosome complement, including two with an XXYY complement. Details of the clinical and cytogenetic features are presented.", "contents": "A chromosome survey of a hospital for the mentally subnormal. A cytogenetic survey of 756 resident, but otherwise unselected, mentally retarded patients in a Scottish hospital is reported. The karyotypes of all patients were examined using orcein-stained cells, and those found to be abnormal, other than those with standard trisomy 21, were further investigated using a banding technique. A total of 103 patients were found to have an abnormal chromosome complement, of whom 91 had Down's syndrome (including six with translocations), six had some other autosomal abnormality, and six had an abnormality of the sex chromosome complement, including two with an XXYY complement. Details of the clinical and cytogenetic features are presented."} {"id": "PMID:158448", "title": "Immunological and purine enzyme studies on hyperuricaemic and normouricaemic patients with Down's syndrome.", "content": "Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated with hyperuricaemia. Immunological studies involving serum immunoglobulins, natural E. coli antibodies, test immunization with pneumococcal polysaccharide type III (PnPS), in vitro lymphocyte transformation to mitogens, and pokeweed mitogen (PWM) induced immunoglobulin production showed no difference between hyperuricaemic or normouricaemic Down's patients and institutionalized controls. The Down's patients had higher serum IgA, IgG and IgE, and some also produced more immunoglobulin in PWM-stimulated lymphocyte cultures when compared to normal healthy controls. However, both patients with Down's syndrome and the institutionalized controls had significantly lower responses to PnPs than normal healthy controls. The only deficiency confined to the Down's patients was a signficant depression in delayed hypersensitivity to dinitrochlorobenzene. These findings indicate that the in vivo abnormality of depressed cellular and humoral immunity in Down's patients is not paralleled by in vitro function as measured by PHA lymphocyte transformation and immunoglobulin production by PWM-stimulated lymphocytes. There is also no apparent link between a putative defect in purine metabolism in Down's patients and any immunological abnormalities.", "contents": "Immunological and purine enzyme studies on hyperuricaemic and normouricaemic patients with Down's syndrome. Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated with hyperuricaemia. Immunological studies involving serum immunoglobulins, natural E. coli antibodies, test immunization with pneumococcal polysaccharide type III (PnPS), in vitro lymphocyte transformation to mitogens, and pokeweed mitogen (PWM) induced immunoglobulin production showed no difference between hyperuricaemic or normouricaemic Down's patients and institutionalized controls. The Down's patients had higher serum IgA, IgG and IgE, and some also produced more immunoglobulin in PWM-stimulated lymphocyte cultures when compared to normal healthy controls. However, both patients with Down's syndrome and the institutionalized controls had significantly lower responses to PnPs than normal healthy controls. The only deficiency confined to the Down's patients was a signficant depression in delayed hypersensitivity to dinitrochlorobenzene. These findings indicate that the in vivo abnormality of depressed cellular and humoral immunity in Down's patients is not paralleled by in vitro function as measured by PHA lymphocyte transformation and immunoglobulin production by PWM-stimulated lymphocytes. There is also no apparent link between a putative defect in purine metabolism in Down's patients and any immunological abnormalities."} {"id": "PMID:158449", "title": "Relationship of donor-specific mixed lymphocyte culture reactivity to graft function in recipients of cadaveric renal allografts.", "content": "The response of twelve cadaveric renal allograft recipients was serially studied in one-way MLC using the specific donor spleen lymphocytes as stimulating cells. The stimulation index (SI) progressively decreased between the second and the eighteenth post-transplantation week in the presence of normal plasma. The appearance of MLC non-reactivity (SI of less than 2.3) correlated well with the achievement of excellent graft function. In nine recipients allograft rejections have not occurred once the non-reactive state in cultures with normal plasma was established. In two of the recipients reactivity reappeared after an interval of non-reactive phase. In both instances rejection followed such reactivity and non-reactivity followed successful management of rejection. In one patient severe irreversible allograft rejection occurred in spite of the appearance of an early MLC non-reactive phase. This patient developed donor-specific lymphocytotoxic antibodies and his rejection was perhaps of antibody mediated type. Donor-specific MLC reactivity may represent cellular immune response of host to an allograft and predict cellular allograft rejection.", "contents": "Relationship of donor-specific mixed lymphocyte culture reactivity to graft function in recipients of cadaveric renal allografts. The response of twelve cadaveric renal allograft recipients was serially studied in one-way MLC using the specific donor spleen lymphocytes as stimulating cells. The stimulation index (SI) progressively decreased between the second and the eighteenth post-transplantation week in the presence of normal plasma. The appearance of MLC non-reactivity (SI of less than 2.3) correlated well with the achievement of excellent graft function. In nine recipients allograft rejections have not occurred once the non-reactive state in cultures with normal plasma was established. In two of the recipients reactivity reappeared after an interval of non-reactive phase. In both instances rejection followed such reactivity and non-reactivity followed successful management of rejection. In one patient severe irreversible allograft rejection occurred in spite of the appearance of an early MLC non-reactive phase. This patient developed donor-specific lymphocytotoxic antibodies and his rejection was perhaps of antibody mediated type. Donor-specific MLC reactivity may represent cellular immune response of host to an allograft and predict cellular allograft rejection."} {"id": "PMID:158450", "title": "Selective defects in T cell function in ataxia-telangiectasia.", "content": "We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.", "contents": "Selective defects in T cell function in ataxia-telangiectasia. We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function."} {"id": "PMID:158473", "title": "Translocation and other recombination events involving the tetracycline-resistance element Tn10.", "content": "Insertions of Tn10 are characterized by the presence of a direct repetition of a 9-bp target gene sequence on either side the insertion. The occurrence of these repetitions undoubtedly reflects an important feature of the way in which DNA molecules are broken and joined during translocation. Our experiments further suggest, however, that these 9-bp sequences are probably not responsible for Tn10-insertion specificity and that their presence is not required for normal Tn10 translocation elsewhere. We therefore suggest that the genetic information which controls the quality and quantity of Tn10 translocation actually resides somewhere other than these 9-bp sequences. We presume that much of this information lies within the ends of Tn10 itself and that signals on the target DNA which guide Tn10 to preferred positions must occur near, but not actually at, the eventual physical site of the integration event. Consideration of Tn10-promoted deletions and inversions reemphasizes the role of these ends in Tn10-promoted recombination events. Since Tn10-promoted events almost always consist in joining the physical end of one of the putative IS sequences of Tn10 to some other DNA segment, one comes again to the conclusion that these ends must contain important genetic information governing recombination events.", "contents": "Translocation and other recombination events involving the tetracycline-resistance element Tn10. Insertions of Tn10 are characterized by the presence of a direct repetition of a 9-bp target gene sequence on either side the insertion. The occurrence of these repetitions undoubtedly reflects an important feature of the way in which DNA molecules are broken and joined during translocation. Our experiments further suggest, however, that these 9-bp sequences are probably not responsible for Tn10-insertion specificity and that their presence is not required for normal Tn10 translocation elsewhere. We therefore suggest that the genetic information which controls the quality and quantity of Tn10 translocation actually resides somewhere other than these 9-bp sequences. We presume that much of this information lies within the ends of Tn10 itself and that signals on the target DNA which guide Tn10 to preferred positions must occur near, but not actually at, the eventual physical site of the integration event. Consideration of Tn10-promoted deletions and inversions reemphasizes the role of these ends in Tn10-promoted recombination events. Since Tn10-promoted events almost always consist in joining the physical end of one of the putative IS sequences of Tn10 to some other DNA segment, one comes again to the conclusion that these ends must contain important genetic information governing recombination events."} {"id": "PMID:158482", "title": "Fibrogenesis and biosynthesis of elastin in cartilage.", "content": "This study presents direct evidence that dissociated chondroblasts from rabbit ear cartilage grown in vitro are capable of synthesizing insoluble elastin. Ultrastructural examination indicated that at an early stage of tissue development, elastogenesis is initiated producing a form of primary fibrils which later condense into an electron dense amorphous material which, unlike other elastin-containing tissues, is heavily stained by metal cations and lacks peripheral microfibrils. Native elastic fibrils and the mature elastic fiber bundles are both susceptible to elastase digestion. Transmission electronmicroscopy demonstrated the presence of many intracellular filaments all showing a substructural organization and localized in close proximity to the nucleus. Their possible contractile nature is discussed. Amino acid analysis of cartilage elastin and of the elastin synthesized in vitro revealed a close chemical similarity between the two molecules. Ultrastructural analysis of the in vitro elastin demonstrated a substructural organization quite similar to that of the elastin observed in an in vivo system.", "contents": "Fibrogenesis and biosynthesis of elastin in cartilage. This study presents direct evidence that dissociated chondroblasts from rabbit ear cartilage grown in vitro are capable of synthesizing insoluble elastin. Ultrastructural examination indicated that at an early stage of tissue development, elastogenesis is initiated producing a form of primary fibrils which later condense into an electron dense amorphous material which, unlike other elastin-containing tissues, is heavily stained by metal cations and lacks peripheral microfibrils. Native elastic fibrils and the mature elastic fiber bundles are both susceptible to elastase digestion. Transmission electronmicroscopy demonstrated the presence of many intracellular filaments all showing a substructural organization and localized in close proximity to the nucleus. Their possible contractile nature is discussed. Amino acid analysis of cartilage elastin and of the elastin synthesized in vitro revealed a close chemical similarity between the two molecules. Ultrastructural analysis of the in vitro elastin demonstrated a substructural organization quite similar to that of the elastin observed in an in vivo system."} {"id": "PMID:158484", "title": "Chondroitin sulfates and proteoglycans from normal and arthrosic human cartilage.", "content": "The structure of chondroitin sulfates and proteoglycans extracted from human normal young and adult cartilages and also from human arthrosic cartilages are reported. The adult articular cartilage contains almost exclusively chondroitin 6-sulfate, whereas the normal young and the arthrosic cartilage chondroitin sulfates are hybrid polymers, containing 4-sulfated and 6-sulfated disaccharide units, distributed in a quite random way along the molecules. The young cartilage proteoglycans also differ from the adult cartilage proteoglycans by their contents of keratan sulfate, the relative proportion of nonaggregating proteoglycans and electrophoretic migration in agarose gel slabs. The proteoglycans from arthrosic cartilages are very similar to those from young normal cartilages. Such changes in composition could lead to alterations in the proportion and size of the aggregates they form in the cartilages, furnishing the conditions for the processes of growth and calcification to occur.", "contents": "Chondroitin sulfates and proteoglycans from normal and arthrosic human cartilage. The structure of chondroitin sulfates and proteoglycans extracted from human normal young and adult cartilages and also from human arthrosic cartilages are reported. The adult articular cartilage contains almost exclusively chondroitin 6-sulfate, whereas the normal young and the arthrosic cartilage chondroitin sulfates are hybrid polymers, containing 4-sulfated and 6-sulfated disaccharide units, distributed in a quite random way along the molecules. The young cartilage proteoglycans also differ from the adult cartilage proteoglycans by their contents of keratan sulfate, the relative proportion of nonaggregating proteoglycans and electrophoretic migration in agarose gel slabs. The proteoglycans from arthrosic cartilages are very similar to those from young normal cartilages. Such changes in composition could lead to alterations in the proportion and size of the aggregates they form in the cartilages, furnishing the conditions for the processes of growth and calcification to occur."} {"id": "PMID:158486", "title": "Circadian rhythms and the urinary excretion of acid glycosaminoglycans in normal human adults.", "content": "Urine from normal human adults (11 males, 4 females) was collected for 24 hours in four-hour samples, commencing at 08.00 hours. The urine volume, and concentrations of chondroitin sulfate, heparan sulfate, cetylpyridinium turbidity, and creatinine were measured on every sample. Concentrations and total output of glycosaminoglycans were significantly higher in male urine than in female urine. Chondroitin sulfate total output/four hours showed a significant negative correlation with creatinine concentration in males, but not in females. A testicular hyaluronidase is implicated. No such correlation was observed for heparan sulfate. Glycosaminoglycans are filtered into the urine. Plasma clearances are very low. Heparan sulfate is excreted with a circadian rhythm, as is glycosaminoglycan assayed by cetyl pyridinium turbidity. Peak excretions are at 06.00 and 10.00 hours respectively. Chondroitin sulfate excretion is not rhythmic in the male, perhaps because hyaluronidase activity in the urine complicates the assay. A rhythm may be present in the female.", "contents": "Circadian rhythms and the urinary excretion of acid glycosaminoglycans in normal human adults. Urine from normal human adults (11 males, 4 females) was collected for 24 hours in four-hour samples, commencing at 08.00 hours. The urine volume, and concentrations of chondroitin sulfate, heparan sulfate, cetylpyridinium turbidity, and creatinine were measured on every sample. Concentrations and total output of glycosaminoglycans were significantly higher in male urine than in female urine. Chondroitin sulfate total output/four hours showed a significant negative correlation with creatinine concentration in males, but not in females. A testicular hyaluronidase is implicated. No such correlation was observed for heparan sulfate. Glycosaminoglycans are filtered into the urine. Plasma clearances are very low. Heparan sulfate is excreted with a circadian rhythm, as is glycosaminoglycan assayed by cetyl pyridinium turbidity. Peak excretions are at 06.00 and 10.00 hours respectively. Chondroitin sulfate excretion is not rhythmic in the male, perhaps because hyaluronidase activity in the urine complicates the assay. A rhythm may be present in the female."} {"id": "PMID:158488", "title": "The relationship between interventricular septum thickness and its function. An echocardiographic study.", "content": "By means of a single beam echocardiography the authors investigated the relationship between interventricular septum diastolic thickness and its function, evaulated as percentage of systolic thickening. 55 persons were examined, partly healthy subjects and partly those with various cardiac diseases, excluding the cases with reversed septum motion or local septum dyskinesis. The found correlation between septum thickness and its function was exponential and statistically significant (p less than 0.001; r = --0.805). Thus, the hypothesis concerning the quantitatively dependent deterioration of the septum function on the degree of its hypertrophy was confirmed.", "contents": "The relationship between interventricular septum thickness and its function. An echocardiographic study. By means of a single beam echocardiography the authors investigated the relationship between interventricular septum diastolic thickness and its function, evaulated as percentage of systolic thickening. 55 persons were examined, partly healthy subjects and partly those with various cardiac diseases, excluding the cases with reversed septum motion or local septum dyskinesis. The found correlation between septum thickness and its function was exponential and statistically significant (p less than 0.001; r = --0.805). Thus, the hypothesis concerning the quantitatively dependent deterioration of the septum function on the degree of its hypertrophy was confirmed."} {"id": "PMID:158489", "title": "Inhibition of ADP-induced aggregation of human platelets by beta, gamma-methylene-ATP.", "content": "Like ATP the analogue beta, gamma-methylene-ATP (AMP-PCP) is shown to be an inhibitor of both ADP-induced shape change and aggregation of human platelets. The effect of AMP-PCP on aggregation is not dependent on its conversion to adenosine, though in the presence of plasma adenosine is produced and the inhibitory effect is enhanced. Since AMP-PCP cannot be enzymatically cleaved at the beta, gamma-position the inhibitory effect cannot be attributed to utilisation of the analogue by a surface-located ATPase as has been suggested for ATP. Alternative explanations for the effect are considered with respect to some current theories of ADP-induced platelet aggregation.", "contents": "Inhibition of ADP-induced aggregation of human platelets by beta, gamma-methylene-ATP. Like ATP the analogue beta, gamma-methylene-ATP (AMP-PCP) is shown to be an inhibitor of both ADP-induced shape change and aggregation of human platelets. The effect of AMP-PCP on aggregation is not dependent on its conversion to adenosine, though in the presence of plasma adenosine is produced and the inhibitory effect is enhanced. Since AMP-PCP cannot be enzymatically cleaved at the beta, gamma-position the inhibitory effect cannot be attributed to utilisation of the analogue by a surface-located ATPase as has been suggested for ATP. Alternative explanations for the effect are considered with respect to some current theories of ADP-induced platelet aggregation."} {"id": "PMID:158496", "title": "ECG alterations with progressive left ventricular hypertrophy in spontaneous hypertension.", "content": "Although many ECG criteria exist for diagnosis of left ventricular hypertrophy (LVH) in hypertensive man, little is known of which specific ECG changes accompany progression of LVH with duration of hypertension. The spontaneously hypertensive rat (SHR) provides the best animal model thus far developed for studying this process since these animals demonstrate a progressive increase in left ventricular/body weight ratio with age. Electrocardiograms were performed under light ether anesthesia in four age groups of SHR and two normotensive Wistar strains (NR and WKY). Analysis of variance for two factors (rat strain and age) revealed progressively increased QRS and P-wave duration and delay in intrinsicoid deflection in SHR (p less than 0.001). Bipeak P-wave notching was also noted in SHR similar to left atrial abnormality in hypertensive man. Thus, specific ECG indices can be identified in association with the known progressive increase in left ventricular mass in SHR and should provide a better means to understand evolving ECG changes in LVH.", "contents": "ECG alterations with progressive left ventricular hypertrophy in spontaneous hypertension. Although many ECG criteria exist for diagnosis of left ventricular hypertrophy (LVH) in hypertensive man, little is known of which specific ECG changes accompany progression of LVH with duration of hypertension. The spontaneously hypertensive rat (SHR) provides the best animal model thus far developed for studying this process since these animals demonstrate a progressive increase in left ventricular/body weight ratio with age. Electrocardiograms were performed under light ether anesthesia in four age groups of SHR and two normotensive Wistar strains (NR and WKY). Analysis of variance for two factors (rat strain and age) revealed progressively increased QRS and P-wave duration and delay in intrinsicoid deflection in SHR (p less than 0.001). Bipeak P-wave notching was also noted in SHR similar to left atrial abnormality in hypertensive man. Thus, specific ECG indices can be identified in association with the known progressive increase in left ventricular mass in SHR and should provide a better means to understand evolving ECG changes in LVH."} {"id": "PMID:158497", "title": "Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization.", "content": "We have developed an enzymatic technique for isolating human intestinal mucosal lymphoid cells. This method was found to be superior to mechanical methods in regard to cell yield and survival. It is based on treating mucosa with serum-free solutions containing collagenase and deoxyribonuclease, followed by isolating the lymphoid cells through centrifugation steps involving fetal calf serum and ficoll-hypaque. Exposure of peripheral blood lymphocytes to the components of the enzymatic solution did not appreciably alter their uptake of tritiated thymidine in the presence or absence of mitogens. Application of the method to derive lymphoid cells from Crohn's disease, ulcerative colitis, and normal intestinal mucosa has shown that gut mucosal lymphocytes from inflammatory bowel disease (1) exceed the number of those from normal mucosa by a factor of 3 to 5; (2) show different degrees of tritiated thymidine uptake, spontaneously and in response to mitogens, depending upon the time they are harvested during the dissociation process; (3) are better stimulators than responders in the allogeneic mixed lymphocyte reaction; (4) generate suppressor cell activity comparable to that of peripheral blood lymphocytes; (5) cannot, in contrast to peripheral blood lymphocytes, generate antibody-dependent cell mediated cytotoxicity; and (6) produce an average of 5 times more IgM than equal numbers of peripheral blood lymphocytes.", "contents": "Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization. We have developed an enzymatic technique for isolating human intestinal mucosal lymphoid cells. This method was found to be superior to mechanical methods in regard to cell yield and survival. It is based on treating mucosa with serum-free solutions containing collagenase and deoxyribonuclease, followed by isolating the lymphoid cells through centrifugation steps involving fetal calf serum and ficoll-hypaque. Exposure of peripheral blood lymphocytes to the components of the enzymatic solution did not appreciably alter their uptake of tritiated thymidine in the presence or absence of mitogens. Application of the method to derive lymphoid cells from Crohn's disease, ulcerative colitis, and normal intestinal mucosa has shown that gut mucosal lymphocytes from inflammatory bowel disease (1) exceed the number of those from normal mucosa by a factor of 3 to 5; (2) show different degrees of tritiated thymidine uptake, spontaneously and in response to mitogens, depending upon the time they are harvested during the dissociation process; (3) are better stimulators than responders in the allogeneic mixed lymphocyte reaction; (4) generate suppressor cell activity comparable to that of peripheral blood lymphocytes; (5) cannot, in contrast to peripheral blood lymphocytes, generate antibody-dependent cell mediated cytotoxicity; and (6) produce an average of 5 times more IgM than equal numbers of peripheral blood lymphocytes."} {"id": "PMID:158500", "title": "[Cement ulcers].", "content": "It is told of a toxic contact dermatitis of a mason with hitherto intact skin. One is searching for the reason of this rarely appearing skin damage by taking into consideration the chemical process during the cement preparation as well as in the following working process. The low number of cases known so far in relation to the millions of tons of processed cement on the one hand and the serious professional consequences for the persons concerned on the other have caused us to discuss once again the causal correlations in this essay.", "contents": "[Cement ulcers]. It is told of a toxic contact dermatitis of a mason with hitherto intact skin. One is searching for the reason of this rarely appearing skin damage by taking into consideration the chemical process during the cement preparation as well as in the following working process. The low number of cases known so far in relation to the millions of tons of processed cement on the one hand and the serious professional consequences for the persons concerned on the other have caused us to discuss once again the causal correlations in this essay."} {"id": "PMID:158501", "title": "[Persistance of epidermal sensitizations in occupational allergic contact eczemas (author's transl)].", "content": "Allergic contact eczemas occur in the region of Halle (DDR) in the chemical industry, in health services, in architecture, in the metal industry and in local logistics. In 732 cases of occupational eczemas, \"para\"-substances, chromates, plastic materials and adhesives, technical oils and fats, turpentine oil, dyestuffs and disinfectants were the principal noxious substances. Phenothiazine, synthetic resins and adhesives, nickel, turpentine oil, chromates, iodine, p-phenylendiamine, mercury compounds, etc. cause epidermal sensitizations that persist up to 10-12 years. Sensitized persons must strictly avoid these noxious substances, even in their para-professional shere; repeated tests should be abandoned because the epidermal sensitization might be \"boosted\".", "contents": "[Persistance of epidermal sensitizations in occupational allergic contact eczemas (author's transl)]. Allergic contact eczemas occur in the region of Halle (DDR) in the chemical industry, in health services, in architecture, in the metal industry and in local logistics. In 732 cases of occupational eczemas, \"para\"-substances, chromates, plastic materials and adhesives, technical oils and fats, turpentine oil, dyestuffs and disinfectants were the principal noxious substances. Phenothiazine, synthetic resins and adhesives, nickel, turpentine oil, chromates, iodine, p-phenylendiamine, mercury compounds, etc. cause epidermal sensitizations that persist up to 10-12 years. Sensitized persons must strictly avoid these noxious substances, even in their para-professional shere; repeated tests should be abandoned because the epidermal sensitization might be \"boosted\"."} {"id": "PMID:158502", "title": "[Lyell' syndrome: a review with special regard to the form caused by drugs (author's transl)].", "content": "The clinical evolution of Lyell' syndrome (LS), its complications, the histological findings, the nosological position and the differentiation from erythema exsudativum multiforme are dealt with. There are at least two etiological forms of LS: the LS caused by staphylococci, and the LS caused by drugs. The former mainly occurs in children, and is caused by staphylococci of the phagous group II, while the latter is mainly caused by sulfonamides, pyrazolones, penicillines, barbiturates and salicylates. The causative responsibility of a certain drug can be proved by three criteria: 1. Relapse of LS after exposure to the same drug. 2. Allergy to the drug taken before the onset of LS. 3. Positive allergy tests. The hypothesis concerning the pathogenesis of LS caused by drugs, the differential diagnosis and therapeutical guidelines are dealt with.", "contents": "[Lyell' syndrome: a review with special regard to the form caused by drugs (author's transl)]. The clinical evolution of Lyell' syndrome (LS), its complications, the histological findings, the nosological position and the differentiation from erythema exsudativum multiforme are dealt with. There are at least two etiological forms of LS: the LS caused by staphylococci, and the LS caused by drugs. The former mainly occurs in children, and is caused by staphylococci of the phagous group II, while the latter is mainly caused by sulfonamides, pyrazolones, penicillines, barbiturates and salicylates. The causative responsibility of a certain drug can be proved by three criteria: 1. Relapse of LS after exposure to the same drug. 2. Allergy to the drug taken before the onset of LS. 3. Positive allergy tests. The hypothesis concerning the pathogenesis of LS caused by drugs, the differential diagnosis and therapeutical guidelines are dealt with."} {"id": "PMID:158503", "title": "[New German legislation on occupational dermatoses (author's transl)].", "content": "According to the new German legislation on occupational dermatoses of January 1, 1977, a person suffering from an occupational dermatosis can be idemnified only in case that occupational disease \"has compelled him to abstain from all activities that have caused or might be responsible of, the appearance, the aggravation or the recurrence of that disease\".", "contents": "[New German legislation on occupational dermatoses (author's transl)]. According to the new German legislation on occupational dermatoses of January 1, 1977, a person suffering from an occupational dermatosis can be idemnified only in case that occupational disease \"has compelled him to abstain from all activities that have caused or might be responsible of, the appearance, the aggravation or the recurrence of that disease\"."} {"id": "PMID:158504", "title": "[Polyvalent contact allergy in a florist].", "content": "A female florist, who ran a flowershop from 1954 to 1966 had to quit her job because of her known contact allergy due to chrysanthemums and primrose. Though in the meantime 12 years had passed she suffered occasionally from redness of the pharynx and stomachache after ingestion of tea prepared from yarrow and camomile. Cleaning off her garden from weeds and frequently followed by swelling of her face and pruritus. After epicutaneous testing she developed positive reactions to chrysanthemum as well as cross reactions to sunflower, arnica, camomile, yarrow, tansy, mugwort and frullania (this lichen does not occur in the Northern part of Germany). Patch test with primin revealed the persistence of the highgrade hypersensitivity to Primula.", "contents": "[Polyvalent contact allergy in a florist]. A female florist, who ran a flowershop from 1954 to 1966 had to quit her job because of her known contact allergy due to chrysanthemums and primrose. Though in the meantime 12 years had passed she suffered occasionally from redness of the pharynx and stomachache after ingestion of tea prepared from yarrow and camomile. Cleaning off her garden from weeds and frequently followed by swelling of her face and pruritus. After epicutaneous testing she developed positive reactions to chrysanthemum as well as cross reactions to sunflower, arnica, camomile, yarrow, tansy, mugwort and frullania (this lichen does not occur in the Northern part of Germany). Patch test with primin revealed the persistence of the highgrade hypersensitivity to Primula."} {"id": "PMID:158505", "title": "[Allergen specificity in protein dermatitis (Hjorth)].", "content": "Combination of animal specific antigen reactions and tissue specific factors were found in a female patient with protein dermatitis (Jorth). Positive reactions to muscle-tissue of pigs but no reaction to renal tissue of pigs, tested intracutaneously were obtained. These observations suggest, that muscle specific aminoacids 3-methyl-histidine, monomethyl lysin and tri-methyl-lysin cause antigen reactions.", "contents": "[Allergen specificity in protein dermatitis (Hjorth)]. Combination of animal specific antigen reactions and tissue specific factors were found in a female patient with protein dermatitis (Jorth). Positive reactions to muscle-tissue of pigs but no reaction to renal tissue of pigs, tested intracutaneously were obtained. These observations suggest, that muscle specific aminoacids 3-methyl-histidine, monomethyl lysin and tri-methyl-lysin cause antigen reactions."} {"id": "PMID:158506", "title": "[Pilonidal sinus in a hairdresser].", "content": "The patient is a 28-year-old hairdresser who began his apprenticeship after school and has worked in this profession since then. Within the last two years fistulas formed on both hands between the second and third fingers in which hairs accumulated during his daily work of cutting hair. So an infection with lymphadenitis occurred. The excision lead to the histological result of an interdigital pilonidal-sinus.", "contents": "[Pilonidal sinus in a hairdresser]. The patient is a 28-year-old hairdresser who began his apprenticeship after school and has worked in this profession since then. Within the last two years fistulas formed on both hands between the second and third fingers in which hairs accumulated during his daily work of cutting hair. So an infection with lymphadenitis occurred. The excision lead to the histological result of an interdigital pilonidal-sinus."} {"id": "PMID:158508", "title": "[Recognition of a skin disease as an occupational disease according to the current legislation].", "content": "Admission of the insurance qualifying occupational skin disease (No. 5101 of Schedule 1 of the Occupational Disease Regulations = BeKV) has as its pre-requisite the availability of the medical evidence. The beginning of the period qualifying for insurance benefit shall be determined retrospectively. A hazardous activity appertains even if only a minor portion of the field of activity is the cause of the disease. Qualifying for insurance benefits requires that this activity shall have been finally given up and that the same or other hazardous activities are avoided in the future. This prognosis must have a good measure of probability. Otherwise, if the insured acts in bad faith, a pension may be withheld; if the insured acted in good faith a worsening of a syndrome by the hazardous activity (whether carried on as occupation or on one's own behalf) is not compensated for. The insurance qualifying date, furthermore, is dependent on the necessity for first-time medical treatment, medicines or therapeutic agents, or the incapacity for work, or the arising of a pension-qualifying reduction in earning power.", "contents": "[Recognition of a skin disease as an occupational disease according to the current legislation]. Admission of the insurance qualifying occupational skin disease (No. 5101 of Schedule 1 of the Occupational Disease Regulations = BeKV) has as its pre-requisite the availability of the medical evidence. The beginning of the period qualifying for insurance benefit shall be determined retrospectively. A hazardous activity appertains even if only a minor portion of the field of activity is the cause of the disease. Qualifying for insurance benefits requires that this activity shall have been finally given up and that the same or other hazardous activities are avoided in the future. This prognosis must have a good measure of probability. Otherwise, if the insured acts in bad faith, a pension may be withheld; if the insured acted in good faith a worsening of a syndrome by the hazardous activity (whether carried on as occupation or on one's own behalf) is not compensated for. The insurance qualifying date, furthermore, is dependent on the necessity for first-time medical treatment, medicines or therapeutic agents, or the incapacity for work, or the arising of a pension-qualifying reduction in earning power."} {"id": "PMID:158511", "title": "[Occupational dermatoses in workers of a prefabricated houses' factory].", "content": "Dermatological examinations in workers of the Dwelling Houses Factory were performed 1-5 years apart. On the whole 1011 subjects have been examined. The most frequent professional disease was oil acne brought about by the contact with anti-adhesive oils. The effects of the kind of anti-adhesive oils, the post at work (degree of exposure to the contact with oil) as well as the work period on the acne changes have been analyzed. It was found that the most acnogenic preparation was formol, then ceramic oil while isoform proved to be much less active. It was shown that the longer the work period the more decreased the oil acne morbidity. A low percentage of allergic contact eruption (1.8%) is probably related to the highly mechanized production cycle.", "contents": "[Occupational dermatoses in workers of a prefabricated houses' factory]. Dermatological examinations in workers of the Dwelling Houses Factory were performed 1-5 years apart. On the whole 1011 subjects have been examined. The most frequent professional disease was oil acne brought about by the contact with anti-adhesive oils. The effects of the kind of anti-adhesive oils, the post at work (degree of exposure to the contact with oil) as well as the work period on the acne changes have been analyzed. It was found that the most acnogenic preparation was formol, then ceramic oil while isoform proved to be much less active. It was shown that the longer the work period the more decreased the oil acne morbidity. A low percentage of allergic contact eruption (1.8%) is probably related to the highly mechanized production cycle."} {"id": "PMID:158512", "title": "[Gonococcal pharyngitis in a woman with genital gonorrhea].", "content": "Gonococci were isolated from pharyngeal swabs in a woman suffering from genital gonorrhoea. She admitted orogenital contact at her most recent intercourse. A single dose treatment with spectinomycin cured the genital and pharyngeal infections.", "contents": "[Gonococcal pharyngitis in a woman with genital gonorrhea]. Gonococci were isolated from pharyngeal swabs in a woman suffering from genital gonorrhoea. She admitted orogenital contact at her most recent intercourse. A single dose treatment with spectinomycin cured the genital and pharyngeal infections."} {"id": "PMID:158513", "title": "Contact sensitivity to phenylglycidyl ether.", "content": "From among 40 workers with dermatitis who did not have contact with phenylglycidyl ether but worked with epoxy resins, 5 were positive to Epidian 5 and phenylglycidyl ether. Cross reactions between these contactants were noted in 3 of the 17 guinea pigs with primary sensitization to epoxy resin or the tested diluent. For 58 persons coming into contact with phenylglycidyl ether the frequency of sensitization to the contactant was determined and the mean period between starting work and the occurrence of dermatitis was calculated.", "contents": "Contact sensitivity to phenylglycidyl ether. From among 40 workers with dermatitis who did not have contact with phenylglycidyl ether but worked with epoxy resins, 5 were positive to Epidian 5 and phenylglycidyl ether. Cross reactions between these contactants were noted in 3 of the 17 guinea pigs with primary sensitization to epoxy resin or the tested diluent. For 58 persons coming into contact with phenylglycidyl ether the frequency of sensitization to the contactant was determined and the mean period between starting work and the occurrence of dermatitis was calculated."} {"id": "PMID:158514", "title": "[The allergenic nature of p-tert-butylphenolformaldehyde resin].", "content": "Until now allergic contact dermatitis to polychloroprene glues was thought to be caused by uncondensed p-tert.-butylphenol (monomer) or by the p-tert. burylphenol formaldehyde resin molecule (polycondensate) as allergens. This opinion could not be verified. We found the following two contact allergens: 2-hydroxy-5-tert.-butylbenzyl alcohol and a four nuclear-condensate from four p-tert-butylphenol molecules linear combined by methylene bridges.", "contents": "[The allergenic nature of p-tert-butylphenolformaldehyde resin]. Until now allergic contact dermatitis to polychloroprene glues was thought to be caused by uncondensed p-tert.-butylphenol (monomer) or by the p-tert. burylphenol formaldehyde resin molecule (polycondensate) as allergens. This opinion could not be verified. We found the following two contact allergens: 2-hydroxy-5-tert.-butylbenzyl alcohol and a four nuclear-condensate from four p-tert-butylphenol molecules linear combined by methylene bridges."} {"id": "PMID:158517", "title": "[Allergic skin reactions in metallurgic industries (author's transl)].", "content": "The sensitizing properties of additives to cooling emulsions are reviewed. Presently the majority oft skin disorders due to cooling emulsions is of toxic and not of allergic origin. However, the introduction of new chemical substances either as substitutes of nitrites or for a more effective preservation may reverse this ratio especially if potent allergens are used unitentionally. In evaluating the advantage of a new additive its possible sensitizing properties has to be considered.", "contents": "[Allergic skin reactions in metallurgic industries (author's transl)]. The sensitizing properties of additives to cooling emulsions are reviewed. Presently the majority oft skin disorders due to cooling emulsions is of toxic and not of allergic origin. However, the introduction of new chemical substances either as substitutes of nitrites or for a more effective preservation may reverse this ratio especially if potent allergens are used unitentionally. In evaluating the advantage of a new additive its possible sensitizing properties has to be considered."} {"id": "PMID:158518", "title": "Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride.", "content": "Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vitro assays. This initial report describes the results for one of these compounds, Naltrexone. Nalrexone is a relatively nontoxic drug antagonist related to Naloxone which appears to be effective in diminishing the euphoria and dependence upon heroin in clinical studies. With the exception of weak nonspecific DNA damage observed in an E. coli DNA repair test and possibly with WI-38 cells as well, Naltrexone did not demonstrate significant potential for the induction of gene mutations or chromosomal aberrations under the conditions of this evaluation.", "contents": "Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride. Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vitro assays. This initial report describes the results for one of these compounds, Naltrexone. Nalrexone is a relatively nontoxic drug antagonist related to Naloxone which appears to be effective in diminishing the euphoria and dependence upon heroin in clinical studies. With the exception of weak nonspecific DNA damage observed in an E. coli DNA repair test and possibly with WI-38 cells as well, Naltrexone did not demonstrate significant potential for the induction of gene mutations or chromosomal aberrations under the conditions of this evaluation."} {"id": "PMID:158519", "title": "Serotonin as a differentiation signal in early neurogenesis.", "content": "The hypothesis that serotonin (5-HT) influences the onset of differentiation (cessation of division) of prospective 5-HT target neurons during embryogenesis was tested by administering the 5-HT depleting drug p-chlorophenylalanine (pCPA) to pregnant rats and dating the time of last cell division for fetal neurons using long survival 3H-thymidine autoradiography. PCPA specifically retarded the onset of neuronal differentiation in brain regions known to contain 5-HT terminals or to have a high 5-HT content in the adult (5-HT target cells). Conversely, the 'stress' of daily vehicle injections accelerated onset of differentiation in these regions, possibly due to stimulation of 5-HT synthesis by glucocorticoids. These data support the model of 5-HT as a humoral signal for the differentiation of cells later recognized by 5-HT neurons as appropriate targets for synaptogenesis.", "contents": "Serotonin as a differentiation signal in early neurogenesis. The hypothesis that serotonin (5-HT) influences the onset of differentiation (cessation of division) of prospective 5-HT target neurons during embryogenesis was tested by administering the 5-HT depleting drug p-chlorophenylalanine (pCPA) to pregnant rats and dating the time of last cell division for fetal neurons using long survival 3H-thymidine autoradiography. PCPA specifically retarded the onset of neuronal differentiation in brain regions known to contain 5-HT terminals or to have a high 5-HT content in the adult (5-HT target cells). Conversely, the 'stress' of daily vehicle injections accelerated onset of differentiation in these regions, possibly due to stimulation of 5-HT synthesis by glucocorticoids. These data support the model of 5-HT as a humoral signal for the differentiation of cells later recognized by 5-HT neurons as appropriate targets for synaptogenesis."} {"id": "PMID:158521", "title": "Endoscopic therapy of a congenital oesophageal stricture.", "content": "A sixteen months old girl with Down's-Syndrome suffered from congenital oesophageal membrane and segmental oesophageal stricture. In the neonatal period, two other associated malformations of the gastrointestinal tract (malrotation of gut and duodenal web) had been operated successfully. The first endoscopic examination of the eosophagus was performed at the age of sixteen months because of increasing dysphagia. A solid membrane in the lower part of the oesophagus was incised by diathermy. The associated segmental stenosis necessitated repeated bougienages. After this treatment the child developed well without clinical signs of dysphagia.", "contents": "Endoscopic therapy of a congenital oesophageal stricture. A sixteen months old girl with Down's-Syndrome suffered from congenital oesophageal membrane and segmental oesophageal stricture. In the neonatal period, two other associated malformations of the gastrointestinal tract (malrotation of gut and duodenal web) had been operated successfully. The first endoscopic examination of the eosophagus was performed at the age of sixteen months because of increasing dysphagia. A solid membrane in the lower part of the oesophagus was incised by diathermy. The associated segmental stenosis necessitated repeated bougienages. After this treatment the child developed well without clinical signs of dysphagia."} {"id": "PMID:158522", "title": "Adenosine triphosphatase of Aspergillus nidulans: existence of isoenzymes of Ca2+-ATPase.", "content": "Ca2+-ATPase activity increased five- to six fold when the cells were subjected to growth at 37 degrees C in protein hydrolysate-supplemented media as compared to that of the cells grown in minimal media. One major isoenzyme and one minor isoenzyme were present in minimal-medium-grown cells while two major isoenzymes were present in the cells grown in protein-supplemented media. When the cells were subjected to heat stress (43 degrees C), they exhibited significantly decreased activity as compared to 37 degrees C grown cells. However, all the cultures subjected to growth at 43 degrees C showed two isoenzymes independent of growth medium.", "contents": "Adenosine triphosphatase of Aspergillus nidulans: existence of isoenzymes of Ca2+-ATPase. Ca2+-ATPase activity increased five- to six fold when the cells were subjected to growth at 37 degrees C in protein hydrolysate-supplemented media as compared to that of the cells grown in minimal media. One major isoenzyme and one minor isoenzyme were present in minimal-medium-grown cells while two major isoenzymes were present in the cells grown in protein-supplemented media. When the cells were subjected to heat stress (43 degrees C), they exhibited significantly decreased activity as compared to 37 degrees C grown cells. However, all the cultures subjected to growth at 43 degrees C showed two isoenzymes independent of growth medium."} {"id": "PMID:158524", "title": "Kinetics of the reactions between streptokinase, plasmin and alpha 2-antiplasmin.", "content": "Streptokinase reacts very rapidly with human plasmin (rate constant 5.4 S 10(7) M-1 s-1) forming a 1:1 stoichiometric complex which has a dissociation constant of 5 X 10(-11) M. This plasmin-streptokinase complex is 10(5) times less reactive towards alpha 2-antiplasmin than plasmin, the inhibition rate constant being 1.4 X 10(2) M-1 s-1. The loss of reactivity of the streptokinase-plasmin complex towards alpha 2-antiplasmin is independent of the lysine binding sites in plasmin since low-Mr plasmin, which lacks these sites, and plasmin in which the sites have been blocked by 6-aminohexanoic acid, are both equally unreactive towards alpha 2-antiplasmin on reaction with streptokinase. The plasmin-streptokinase complex binds to Sepharose-lysine and Sepharose-fibrin monomer in the same fashion as free plasmin, showing that the lysine binding sites are fully exposed in the complex. Bovine plasmin is rapidly inhibited by human alpha 2-antiplasmin (k1 = 1.6 X 10(6) M-1 s-1) and similarly loses reactivity towards the inhibitor on complex formation with streptokinase (50% binding at 0.4 microM streptokinase).", "contents": "Kinetics of the reactions between streptokinase, plasmin and alpha 2-antiplasmin. Streptokinase reacts very rapidly with human plasmin (rate constant 5.4 S 10(7) M-1 s-1) forming a 1:1 stoichiometric complex which has a dissociation constant of 5 X 10(-11) M. This plasmin-streptokinase complex is 10(5) times less reactive towards alpha 2-antiplasmin than plasmin, the inhibition rate constant being 1.4 X 10(2) M-1 s-1. The loss of reactivity of the streptokinase-plasmin complex towards alpha 2-antiplasmin is independent of the lysine binding sites in plasmin since low-Mr plasmin, which lacks these sites, and plasmin in which the sites have been blocked by 6-aminohexanoic acid, are both equally unreactive towards alpha 2-antiplasmin on reaction with streptokinase. The plasmin-streptokinase complex binds to Sepharose-lysine and Sepharose-fibrin monomer in the same fashion as free plasmin, showing that the lysine binding sites are fully exposed in the complex. Bovine plasmin is rapidly inhibited by human alpha 2-antiplasmin (k1 = 1.6 X 10(6) M-1 s-1) and similarly loses reactivity towards the inhibitor on complex formation with streptokinase (50% binding at 0.4 microM streptokinase)."} {"id": "PMID:158526", "title": "Primary structure of human fibrinogen and fibrin. Structural studies on NH2-terminal part of B beta chain.", "content": "The cyanogen bromide fragment, N-DSK, containing the NH2-terminal portions of the three chains of fibrinogen, was found to exist in dimeric and polymeric forms. These different forms gave rise to identical chain fragments on reduction and alkylation. The B beta chain of N-DSK from fibrinogen and the beta chain of N-DSK from fibrin were isolated and characterized. The B beta chain fragment has a blocked NH2-terminal residue, and fibrinopeptide B is released on digestion with thrombin. The beta chain fragment has glycine as NH2-terminal residue. The molecular weight of the B beta chain fragment is 12200 as determined by ultracentrifugal analysis. Gel electrophoresis in sodium dodecyl sulphate gave the molecular weights of 14000 and 13000 for the B beta chain and beta chain fragments, respectively. The NH2-terminal B beta chain fragment consists of 118 amino acid residues and the beta chain fragment of 104 residues. The amino acid sequence of beta chain fragment is identical to B beta chain fragment except for the fibrinopeptide B portion. The isolation of a B beta-related fragment (B beta +), with a molecular weight of 30000, is also reported. The presence of B beta + was explained on the basis of incomplete cleavage at the Met-118 residue during treatment with cyanogen bromide. Some functional aspects of the B beta chain fragment are discussed.", "contents": "Primary structure of human fibrinogen and fibrin. Structural studies on NH2-terminal part of B beta chain. The cyanogen bromide fragment, N-DSK, containing the NH2-terminal portions of the three chains of fibrinogen, was found to exist in dimeric and polymeric forms. These different forms gave rise to identical chain fragments on reduction and alkylation. The B beta chain of N-DSK from fibrinogen and the beta chain of N-DSK from fibrin were isolated and characterized. The B beta chain fragment has a blocked NH2-terminal residue, and fibrinopeptide B is released on digestion with thrombin. The beta chain fragment has glycine as NH2-terminal residue. The molecular weight of the B beta chain fragment is 12200 as determined by ultracentrifugal analysis. Gel electrophoresis in sodium dodecyl sulphate gave the molecular weights of 14000 and 13000 for the B beta chain and beta chain fragments, respectively. The NH2-terminal B beta chain fragment consists of 118 amino acid residues and the beta chain fragment of 104 residues. The amino acid sequence of beta chain fragment is identical to B beta chain fragment except for the fibrinopeptide B portion. The isolation of a B beta-related fragment (B beta +), with a molecular weight of 30000, is also reported. The presence of B beta + was explained on the basis of incomplete cleavage at the Met-118 residue during treatment with cyanogen bromide. Some functional aspects of the B beta chain fragment are discussed."} {"id": "PMID:158527", "title": "Investigation of soluble mitochondrial ATPase by the reacting enzyme sedimentation method.", "content": "Soluble mitochondrial ATPase from bovine heart (factor F1) loses its activity during ATP hydrolyses. The inactivation is accelerated by moderate pressure, which is generated in an ultracentrifuge cell. The rate of inactivation slows down if the concentration of the substrate (MgATP) is diminished. ATP hydrolysis proceeds at an almost constant rate if the substrate concentration is as low as 0.05 mM. One intersubunit cross-link formed by dimethylsuberimidate per molecule of factor F1, prevents its inactivation during the ATPase reaction both without pressure and in an ultracentrifuge. Sedimentation coefficients measured by the reacting enzyme centrifugation method of both unmodified factor F1 at a low (about 0.05 mM MgATP) substrate concentration and of its dimethylsuberimidate cross-linked form in the presence of 10 mM MgATP, were determined to be s20, w = 12.4 +/- 0.4 S. The value is the same as that obtained by the conventional boundary sedimentation method in the absence of the substrate. This result testifies to the fact that the conformation of reacting factor F1 in solution is similar to that of the enzyme in the absence of the substrate.", "contents": "Investigation of soluble mitochondrial ATPase by the reacting enzyme sedimentation method. Soluble mitochondrial ATPase from bovine heart (factor F1) loses its activity during ATP hydrolyses. The inactivation is accelerated by moderate pressure, which is generated in an ultracentrifuge cell. The rate of inactivation slows down if the concentration of the substrate (MgATP) is diminished. ATP hydrolysis proceeds at an almost constant rate if the substrate concentration is as low as 0.05 mM. One intersubunit cross-link formed by dimethylsuberimidate per molecule of factor F1, prevents its inactivation during the ATPase reaction both without pressure and in an ultracentrifuge. Sedimentation coefficients measured by the reacting enzyme centrifugation method of both unmodified factor F1 at a low (about 0.05 mM MgATP) substrate concentration and of its dimethylsuberimidate cross-linked form in the presence of 10 mM MgATP, were determined to be s20, w = 12.4 +/- 0.4 S. The value is the same as that obtained by the conventional boundary sedimentation method in the absence of the substrate. This result testifies to the fact that the conformation of reacting factor F1 in solution is similar to that of the enzyme in the absence of the substrate."} {"id": "PMID:158528", "title": "Level and turnover of polyadenylate-containing ribonucleic acid in Neurospora crassa in different steady states of growth.", "content": "Mycelia of Neurospora crassa in a steady state of growth in different media have a ribosomal content proportional to the rate of growth. Moreover, both the percentage of polysomes and the average ribosomal activity are about the same at all different growth rates. The content of polyadenylated RNA was determined in three different conditions of exponential growth, which allowed growth rates that ranged from 0.26 to 0.51 duplications/h, and was found to constitute about the same fraction of total RNA (4.5--5.2%). Using a kinetic approach, an equation was derived which allowed determination of the average half-lives of polyadenylated RNA: in each medium the cultures were labeled from the moment of the inoculation with [32P]orthophosphate and were then given a 10-min pulse with [5-3H]uridine when they were in the exponential phase. It was found that the determined half-lives of polyadenylated RNA vary, depending on the growth medium, between 30 and 60 min, but with no direct correlation with the growth rate. Moreover, the rate of synthesis of polyadenylated RNA relative to that of stable RNA decreased with the growth rate. On the basis of previous data on the rates of synthesis of stable RNA, it was possible to make an evaluation of the absolute rate of synthesis of polyadenylated RNA. Whereas the rate of synthesis of stable ribosomal RNA increases as a function of the square of the number of duplications per hour, the increase in the rate of synthesis of polyadenylated RNA with the growth rate is much less consistent. It is concluded that in Neurospora the growth rate does not depend on the rate of synthesis of mRNA but rather on the rate of synthesis of rRNA, which sets both the ribosomal level and the steady-state level of mRNA.", "contents": "Level and turnover of polyadenylate-containing ribonucleic acid in Neurospora crassa in different steady states of growth. Mycelia of Neurospora crassa in a steady state of growth in different media have a ribosomal content proportional to the rate of growth. Moreover, both the percentage of polysomes and the average ribosomal activity are about the same at all different growth rates. The content of polyadenylated RNA was determined in three different conditions of exponential growth, which allowed growth rates that ranged from 0.26 to 0.51 duplications/h, and was found to constitute about the same fraction of total RNA (4.5--5.2%). Using a kinetic approach, an equation was derived which allowed determination of the average half-lives of polyadenylated RNA: in each medium the cultures were labeled from the moment of the inoculation with [32P]orthophosphate and were then given a 10-min pulse with [5-3H]uridine when they were in the exponential phase. It was found that the determined half-lives of polyadenylated RNA vary, depending on the growth medium, between 30 and 60 min, but with no direct correlation with the growth rate. Moreover, the rate of synthesis of polyadenylated RNA relative to that of stable RNA decreased with the growth rate. On the basis of previous data on the rates of synthesis of stable RNA, it was possible to make an evaluation of the absolute rate of synthesis of polyadenylated RNA. Whereas the rate of synthesis of stable ribosomal RNA increases as a function of the square of the number of duplications per hour, the increase in the rate of synthesis of polyadenylated RNA with the growth rate is much less consistent. It is concluded that in Neurospora the growth rate does not depend on the rate of synthesis of mRNA but rather on the rate of synthesis of rRNA, which sets both the ribosomal level and the steady-state level of mRNA."} {"id": "PMID:158529", "title": "A DNA-dependent ATPase of calf-thymus.", "content": "A DNA-dependent ATPase has been purified from calf thymus. The enzyme hydrolyses ATP and dATP in the presence of heat-denatured DNA. It does not hydrolyse the corresponding nucleoside triphosphates of guanine, uridine and cytosine. The Km values for ATP and dATP are both 0.62 mM. The enzyme requires magnesium or manganese ions. Its sedimentation coefficient is about 4.4 S. The catalytic activity is inhibited by N-ethylmaleimide but is not sensitive to novobiocin and nalidixic acid which are potent inhibitors of bacterial DNA gyrase. In some cases, during purification, chromatographically distinct additional DNA-dependent ATPase activities were detected. Limited proteolysis or covalent modification of the enzyme in the tissues, or during the first steps of its extraction, are probably responsible for the appearance of these chromatographically distinct forms.", "contents": "A DNA-dependent ATPase of calf-thymus. A DNA-dependent ATPase has been purified from calf thymus. The enzyme hydrolyses ATP and dATP in the presence of heat-denatured DNA. It does not hydrolyse the corresponding nucleoside triphosphates of guanine, uridine and cytosine. The Km values for ATP and dATP are both 0.62 mM. The enzyme requires magnesium or manganese ions. Its sedimentation coefficient is about 4.4 S. The catalytic activity is inhibited by N-ethylmaleimide but is not sensitive to novobiocin and nalidixic acid which are potent inhibitors of bacterial DNA gyrase. In some cases, during purification, chromatographically distinct additional DNA-dependent ATPase activities were detected. Limited proteolysis or covalent modification of the enzyme in the tissues, or during the first steps of its extraction, are probably responsible for the appearance of these chromatographically distinct forms."} {"id": "PMID:158530", "title": "Calcium uptake by sarcoplasmic reticulum of rat muscle: inhibition by DDT.", "content": "Sarcoplasmic reticulum fragments capable of accumulating calcium were isolated from rat skeletal muscle by differential and sucrose gradient centrifugation. The ability of these fragments to accumulate calcium was impaired by adding 2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane (DDT) to the assay medium at concentrations of 0.06 to 6 muM. DDT (6 muM) caused a sharp lag in calcium uptake, with an 82% reduction in reaction rate 30 sec after calcium was added and a 62% reduction after one min. Basal ATPase activity of the microsomal fraction was inhibited by DDT but the calcium-stimulated increment of ATP hydrolysis was not. The findings show that DDT hinders calcium uptake by sarcoplasmic reticulum, but by some means other than inhibition of the calcium-stimulated ATPase. An apparent antagonism between DDT and ouabain or oligomycin was indicated. We propose that the presence of the lipid-soluble DDT molecule within the membrane of the sarcoplasmic reticulum interferes with the normal rapid uptake of calcium ions required for muscle relaxation, and that this interference may contribute to loss of muscle control in organisms poisoned by DDT.", "contents": "Calcium uptake by sarcoplasmic reticulum of rat muscle: inhibition by DDT. Sarcoplasmic reticulum fragments capable of accumulating calcium were isolated from rat skeletal muscle by differential and sucrose gradient centrifugation. The ability of these fragments to accumulate calcium was impaired by adding 2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane (DDT) to the assay medium at concentrations of 0.06 to 6 muM. DDT (6 muM) caused a sharp lag in calcium uptake, with an 82% reduction in reaction rate 30 sec after calcium was added and a 62% reduction after one min. Basal ATPase activity of the microsomal fraction was inhibited by DDT but the calcium-stimulated increment of ATP hydrolysis was not. The findings show that DDT hinders calcium uptake by sarcoplasmic reticulum, but by some means other than inhibition of the calcium-stimulated ATPase. An apparent antagonism between DDT and ouabain or oligomycin was indicated. We propose that the presence of the lipid-soluble DDT molecule within the membrane of the sarcoplasmic reticulum interferes with the normal rapid uptake of calcium ions required for muscle relaxation, and that this interference may contribute to loss of muscle control in organisms poisoned by DDT."} {"id": "PMID:158531", "title": "Expression of Ly-6 alloantigen during differentiation of cytotoxic T cells.", "content": "We have prepared anti-Ly-6.2 by immunization of (CBA/Ca X A-Thy-1a)F1 with AKR/Crc lymphocytes and used the antiserum to study heterogencity of peripheral T lymphocytes. The Ly-6 alloantigen is found on all activated cytotoxic T cells studied, directed to a variety of different target antigens. The antiserum reveals heterogeneity among the precursors of T killer cells, i.e. allogeneic precursors are Ly-6-, whereas the generation of cytotoxic cells to hapten-modified syngeneic cells and xenogeneic cells is partially abrogated by serum pretreatment. Precursors of some in vivo primed responses are also Ly-6+. These findings indicate that the expression of Ly-6 antigen is, at least, partially related to the stage of T cell activation. The in vitro proliferative response of T cells to allogeneic Ia antigens is substantially reduced by pretreatment with anti-Ly-6.2 serum suggesting that this antiserum may be a useful tool for the study of heterogeneity in the Ly-1+ pool of T cells.", "contents": "Expression of Ly-6 alloantigen during differentiation of cytotoxic T cells. We have prepared anti-Ly-6.2 by immunization of (CBA/Ca X A-Thy-1a)F1 with AKR/Crc lymphocytes and used the antiserum to study heterogencity of peripheral T lymphocytes. The Ly-6 alloantigen is found on all activated cytotoxic T cells studied, directed to a variety of different target antigens. The antiserum reveals heterogeneity among the precursors of T killer cells, i.e. allogeneic precursors are Ly-6-, whereas the generation of cytotoxic cells to hapten-modified syngeneic cells and xenogeneic cells is partially abrogated by serum pretreatment. Precursors of some in vivo primed responses are also Ly-6+. These findings indicate that the expression of Ly-6 antigen is, at least, partially related to the stage of T cell activation. The in vitro proliferative response of T cells to allogeneic Ia antigens is substantially reduced by pretreatment with anti-Ly-6.2 serum suggesting that this antiserum may be a useful tool for the study of heterogeneity in the Ly-1+ pool of T cells."} {"id": "PMID:158533", "title": "Close association between particular I region-determined cell surface antigens and Ir gene-controlled immune responsiveness to synthetic polypeptides in wild rats.", "content": "The relationship between major histocompatibility complex (MHC) and genetic control of immune responsiveness to the synthetic polypeptides (T,G)-A--L [poly-(LTyr,LGlu)-poly(DLAla)--poly(LLys)] and (H,G)-A--L [poly(LHis,L-Glu)-poly-(DLAla)--poly(LLys)] has been studied in 26 wild rats. The major histocompatibility complex (MHC) genotype frequencies observed were not different from those expected according to the Hardy-Weinberg formula. More than half of the wild rats carried MHC-linked responder Ir-TGAL and Ir-HGAL genes. High or intermediate responsiveness to (T,G)-A--L and high responsiveness to (H,G)-A--L were always found to be associated with particular I region-determined cell surface antigens. These antigens could be identified serologically and by primary and secondary mixed lymphocyte reactions, and were similar or identical to I region products of (T,G)-A--L high responder or (H,G)-A--L intermediate responder inbred rat strains. The strong association between cell surface antigens and immune responsiveness could be due to linkage disequilibrium or to pleiotropy. Since the same I region-determined cell surface structure could be associated either with high or intermediate anti-(T,G)-A--L antibody titers, the presence of the Ia antigen(s) identified did not seem to guarantee high antibody responsiveness to the test antigen.", "contents": "Close association between particular I region-determined cell surface antigens and Ir gene-controlled immune responsiveness to synthetic polypeptides in wild rats. The relationship between major histocompatibility complex (MHC) and genetic control of immune responsiveness to the synthetic polypeptides (T,G)-A--L [poly-(LTyr,LGlu)-poly(DLAla)--poly(LLys)] and (H,G)-A--L [poly(LHis,L-Glu)-poly-(DLAla)--poly(LLys)] has been studied in 26 wild rats. The major histocompatibility complex (MHC) genotype frequencies observed were not different from those expected according to the Hardy-Weinberg formula. More than half of the wild rats carried MHC-linked responder Ir-TGAL and Ir-HGAL genes. High or intermediate responsiveness to (T,G)-A--L and high responsiveness to (H,G)-A--L were always found to be associated with particular I region-determined cell surface antigens. These antigens could be identified serologically and by primary and secondary mixed lymphocyte reactions, and were similar or identical to I region products of (T,G)-A--L high responder or (H,G)-A--L intermediate responder inbred rat strains. The strong association between cell surface antigens and immune responsiveness could be due to linkage disequilibrium or to pleiotropy. Since the same I region-determined cell surface structure could be associated either with high or intermediate anti-(T,G)-A--L antibody titers, the presence of the Ia antigen(s) identified did not seem to guarantee high antibody responsiveness to the test antigen."} {"id": "PMID:158535", "title": "Spontaneous activity and responses of reticular neurones in monoamine-depleted rats.", "content": "Depletion of rat brain serotonin by p-chlorophenylalanine (PCPA) pretreatment, or of monoamines by reserpine pretreatment, was associated with reduced spontaneous firing rates of bulbar reticular neurones. Administration of 5-hydroxytryptophan to PCPA-treated rats reversed the reduction of neuronal activity. It is suggested that the results indicate a tonic excitatory serotoninergic input to a significant proportion of these neurones, which is abolished by serotonin depletion. Responses to serotonin and noradrenaline were greater in PCPA-treated and reserpire-treated rats respectively, indicating the development of supersensitivity.", "contents": "Spontaneous activity and responses of reticular neurones in monoamine-depleted rats. Depletion of rat brain serotonin by p-chlorophenylalanine (PCPA) pretreatment, or of monoamines by reserpine pretreatment, was associated with reduced spontaneous firing rates of bulbar reticular neurones. Administration of 5-hydroxytryptophan to PCPA-treated rats reversed the reduction of neuronal activity. It is suggested that the results indicate a tonic excitatory serotoninergic input to a significant proportion of these neurones, which is abolished by serotonin depletion. Responses to serotonin and noradrenaline were greater in PCPA-treated and reserpire-treated rats respectively, indicating the development of supersensitivity."} {"id": "PMID:158537", "title": "Pimozide and p-chlorophenylalanine blockade in DL-amphetamine and pargyline-treated rats held at two environmental temperatures.", "content": "In rats, treated with DL-amphetamine + monoamine oxidase inhibitor, and held at an ambient temperature of 28.5 degrees C, hyperthermia was completely eliminated by treatment with pimozide + p-chlorophenyl-alanine. The same drugs markedly reduced the hypothermic effects in rats treated similarly at 4 degrees C. Results implied that serotoninergic and dopaminergic neurones were involved in the thermoregulatory effects of amphetamine.", "contents": "Pimozide and p-chlorophenylalanine blockade in DL-amphetamine and pargyline-treated rats held at two environmental temperatures. In rats, treated with DL-amphetamine + monoamine oxidase inhibitor, and held at an ambient temperature of 28.5 degrees C, hyperthermia was completely eliminated by treatment with pimozide + p-chlorophenyl-alanine. The same drugs markedly reduced the hypothermic effects in rats treated similarly at 4 degrees C. Results implied that serotoninergic and dopaminergic neurones were involved in the thermoregulatory effects of amphetamine."} {"id": "PMID:158538", "title": "An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells.", "content": "An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell.", "contents": "An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells. An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell."} {"id": "PMID:158539", "title": "Circadian variation of the streptozotocin-diabetogenic effect in mice.", "content": "Streptozotocin was injected in normal mice every 4 h, during the day. Greatest number of diabetic animals were obtained at 16.00 h (95%) and lowest at 08.00 h (50%). Magnitude of hyperglycemia also showed similar distribution. This effect might be considered when planning its use for both experimental and clinical purposes.", "contents": "Circadian variation of the streptozotocin-diabetogenic effect in mice. Streptozotocin was injected in normal mice every 4 h, during the day. Greatest number of diabetic animals were obtained at 16.00 h (95%) and lowest at 08.00 h (50%). Magnitude of hyperglycemia also showed similar distribution. This effect might be considered when planning its use for both experimental and clinical purposes."} {"id": "PMID:158549", "title": "Treatment of female infertility due to tubal obstruction by operative laparoscopy.", "content": "The advent in recent years of safe endocoagulation (thermocoagulation within the abdomen) has permitted operative laparoscopic treatment of the tubal factor in infertility in selected cases. This paper reviews the results of operative laparoscopy in 223 cases treated for infertility between 1971 and 1976. Tubal occlusion was present in 133 patients before surgical intervention. Following operative laparoscopy, tubal patency was demonstrated in 67% on testing at the time of operation and in 12% at the first postoperative hydrotubation. In only 21% of cases was tubal patency not achieved by these methods. Those cases requiring isthmic salpingostomy, ampullary or isthmic-tubal implantation, or end-to-end anastomosis were further treated by laparotomy and microsurgery. Ninety cases of pelvic endometriosis were treated by a combination treatment of thermocoagulation, ovarian cyst resection, and the antigonadotropin agent, danazol. Ovariolysis, salpingolysis, fimbrioplasty, and salpingostomy can easily be performed using operative laparoscopy as the method of choice with a minimum of complications, shortened hospitalization time (2 days), and the potential for a repeat procedure or a follow-up laparotomy should this be necessary. The pregnancy rate following laparoscopic treatment for the correction of distal tubal occlusion was 30.5% and for endometriosis genitalis externa, 40%. These rates compare favorably with the rates following procedures involving laparotomy and microsurgery for correction of similar lesions.", "contents": "Treatment of female infertility due to tubal obstruction by operative laparoscopy. The advent in recent years of safe endocoagulation (thermocoagulation within the abdomen) has permitted operative laparoscopic treatment of the tubal factor in infertility in selected cases. This paper reviews the results of operative laparoscopy in 223 cases treated for infertility between 1971 and 1976. Tubal occlusion was present in 133 patients before surgical intervention. Following operative laparoscopy, tubal patency was demonstrated in 67% on testing at the time of operation and in 12% at the first postoperative hydrotubation. In only 21% of cases was tubal patency not achieved by these methods. Those cases requiring isthmic salpingostomy, ampullary or isthmic-tubal implantation, or end-to-end anastomosis were further treated by laparotomy and microsurgery. Ninety cases of pelvic endometriosis were treated by a combination treatment of thermocoagulation, ovarian cyst resection, and the antigonadotropin agent, danazol. Ovariolysis, salpingolysis, fimbrioplasty, and salpingostomy can easily be performed using operative laparoscopy as the method of choice with a minimum of complications, shortened hospitalization time (2 days), and the potential for a repeat procedure or a follow-up laparotomy should this be necessary. The pregnancy rate following laparoscopic treatment for the correction of distal tubal occlusion was 30.5% and for endometriosis genitalis externa, 40%. These rates compare favorably with the rates following procedures involving laparotomy and microsurgery for correction of similar lesions."} {"id": "PMID:158551", "title": "[Onychomycoses caused by moulds].", "content": "The authors studied in vitro and in vivo the invasion of the nail keratin by saprophytes. This invasion takes palce in the same way in both cases: mycelian filaments and spores penetrate in the hyponychium, filaments penetrate in the upper part of the tablet, filaments and, as far as some saprophytes are concerned, 'boring hyphae' penetrate in the lower part of the tablet. Those ways of invasion are responsible for the clinical pictures (onychomycosis, pachyonychia, leuconychomycosis). Electron microscopically the mycelian filaments appear to be both intercellular and intracellular. The authors insist in the importance of the criteria of evaluation which allow us to establish the saprophytic origin of onychomycosis.", "contents": "[Onychomycoses caused by moulds]. The authors studied in vitro and in vivo the invasion of the nail keratin by saprophytes. This invasion takes palce in the same way in both cases: mycelian filaments and spores penetrate in the hyponychium, filaments penetrate in the upper part of the tablet, filaments and, as far as some saprophytes are concerned, 'boring hyphae' penetrate in the lower part of the tablet. Those ways of invasion are responsible for the clinical pictures (onychomycosis, pachyonychia, leuconychomycosis). Electron microscopically the mycelian filaments appear to be both intercellular and intracellular. The authors insist in the importance of the criteria of evaluation which allow us to establish the saprophytic origin of onychomycosis."} {"id": "PMID:158552", "title": "[Opportunistic fungi. Demonstration of some cases].", "content": "Demonstration of some cases of mycoses caused by opportunistic fungi.", "contents": "[Opportunistic fungi. Demonstration of some cases]. Demonstration of some cases of mycoses caused by opportunistic fungi."} {"id": "PMID:158560", "title": "[New transducing phage with RNA polymerase beta- and beta'-subunit genes derived from a hybrid phage lambda att80: isolation, genetic analysis and physical mapping].", "content": "A hybrid lambda att 80 phage with the genetic structure lambda (A-J) phi 80 (att-int-xis) imm lambda..cI857s7 is shown to be a convenient vector for creating transducing phages. On the one hand, the restriction analysis indicates that it has 3 restriction sites for EcoRI in comparison with 5 and 9 sites for parental phages lambda and phi 80 respectively. On the other hand, its buoyant density is less than that of phage lambda and under centrifugation it is easier separated from the phage transducing particles. When lambda att 80 prophage was excluded from the bfe locus of Escherichia coli, transducing phages with genes of two RNA polymerase beta-subunits (rpoB and rpoC) were isolated. To identify the latter, a convenient genetic test was worked out. A physical map of lambda att 80 drifd 35 transducing phage, carrying rpoB and rpoC genes has been constructed using endonucleases EcoRI and HindIII. A comparison of this map and the corresponding maps of transducing phages lambda drifd 18 and lambda drifd 47, studied earlier, led to the discovery of two integration sites of phage lambda within the locus bfe spaced apart by about 1800 nucleotide pairs. At all the sites both phages (lambda and lambda att 80) have integrated in the locus bfe in the counter clockwise order.", "contents": "[New transducing phage with RNA polymerase beta- and beta'-subunit genes derived from a hybrid phage lambda att80: isolation, genetic analysis and physical mapping]. A hybrid lambda att 80 phage with the genetic structure lambda (A-J) phi 80 (att-int-xis) imm lambda..cI857s7 is shown to be a convenient vector for creating transducing phages. On the one hand, the restriction analysis indicates that it has 3 restriction sites for EcoRI in comparison with 5 and 9 sites for parental phages lambda and phi 80 respectively. On the other hand, its buoyant density is less than that of phage lambda and under centrifugation it is easier separated from the phage transducing particles. When lambda att 80 prophage was excluded from the bfe locus of Escherichia coli, transducing phages with genes of two RNA polymerase beta-subunits (rpoB and rpoC) were isolated. To identify the latter, a convenient genetic test was worked out. A physical map of lambda att 80 drifd 35 transducing phage, carrying rpoB and rpoC genes has been constructed using endonucleases EcoRI and HindIII. A comparison of this map and the corresponding maps of transducing phages lambda drifd 18 and lambda drifd 47, studied earlier, led to the discovery of two integration sites of phage lambda within the locus bfe spaced apart by about 1800 nucleotide pairs. At all the sites both phages (lambda and lambda att 80) have integrated in the locus bfe in the counter clockwise order."} {"id": "PMID:158557", "title": "Cancer and environment.", "content": "The attention of scientists has been directed mostly to analyze the influence of the environment on tumor induction. However, the external environment can also enhance the reactivity of the host organism towards tumors, by activating several immune mechanisms. Moreover, the host organism is the first \"foreign\" environment with which tumor cells come into contact in a dynamic way, characterized by a continuous evolution.", "contents": "Cancer and environment. The attention of scientists has been directed mostly to analyze the influence of the environment on tumor induction. However, the external environment can also enhance the reactivity of the host organism towards tumors, by activating several immune mechanisms. Moreover, the host organism is the first \"foreign\" environment with which tumor cells come into contact in a dynamic way, characterized by a continuous evolution."} {"id": "PMID:158564", "title": "Enzyme histochemistry of Wallerian degeneration in the immature optic nerve of rabbits.", "content": "A histochemical study was performed on the activity of several phosphatases, esterases and oxidoreductases in the immature optic nerve of rabbits undergoing Wallerian degeneration. Unilateral enucleations of the eye bulb were performed on 7 days old animals and the degenerated optic nerves were examined in rabbits, 5, 23, 63 and 173 days afterwards. The following results were obtained: 1. The reactive cells appearing in the immature optic nerve undergoing Wallerian degeneration exhibit distinctly increased activities of many hydrolytic and oxidoreductive enzymes. 2. The histoenzymic pattern of changes displayed by the reactive cells occurring in the immature, degenerating optic nerve is distinct from and bears no relation to that seen in the normally developing optic nerve. 3. The genetic formation contained in the oligodendroglial cells is not the sole factor safeguarding the transformation of immature and mature oligodendroglia into myelinating cells.", "contents": "Enzyme histochemistry of Wallerian degeneration in the immature optic nerve of rabbits. A histochemical study was performed on the activity of several phosphatases, esterases and oxidoreductases in the immature optic nerve of rabbits undergoing Wallerian degeneration. Unilateral enucleations of the eye bulb were performed on 7 days old animals and the degenerated optic nerves were examined in rabbits, 5, 23, 63 and 173 days afterwards. The following results were obtained: 1. The reactive cells appearing in the immature optic nerve undergoing Wallerian degeneration exhibit distinctly increased activities of many hydrolytic and oxidoreductive enzymes. 2. The histoenzymic pattern of changes displayed by the reactive cells occurring in the immature, degenerating optic nerve is distinct from and bears no relation to that seen in the normally developing optic nerve. 3. The genetic formation contained in the oligodendroglial cells is not the sole factor safeguarding the transformation of immature and mature oligodendroglia into myelinating cells."} {"id": "PMID:158567", "title": "Suppressor T-cells in BCG-infected mice.", "content": "Specific pathogen-free B6D2 hybrid mice were infected with high (10(8) cells, intravenous), moderate (10(6) cells, intravenous), and low 10(3) cells, aerogenic) doses of viable BCG Pasteur. The growth of the BCG in the lungs and spleens of the three groups was followed over a 90-day period and correlated with the level of tuberculin hypersensitivity. Spleen cells were harvested from the three groups of mice at increasing time intervals and filtered through nylon wool to remove adherent cells, and the level of blast transformation after exposure to phytohemagglutinin and purified protein derivative was determined. Early in the BCG infection both the high- and the intermediate-dose groups showed enhanced thymidine incorporation by the spleen cell cultures, followed by a profound depression late in the infection. At this time, both groups of mice were anergic to purified protein derivative injected into footpads. Cell mixing studies demonstrated the presence of a population of suppressor cells in the spleens of the anergic animals. The suppressive abilities of these cells would be ablated by treatment with anti-Thy-1 antiserum and complement. The aerogenically infected mice were unresponsive to purified protein derivative but showed no evidence of suppressor T-cells. The lack of tuberculin sensitivity in these mice seemed to be due to a lack of sensitized T-cells in the spleen rather than to active immunosuppression.", "contents": "Suppressor T-cells in BCG-infected mice. Specific pathogen-free B6D2 hybrid mice were infected with high (10(8) cells, intravenous), moderate (10(6) cells, intravenous), and low 10(3) cells, aerogenic) doses of viable BCG Pasteur. The growth of the BCG in the lungs and spleens of the three groups was followed over a 90-day period and correlated with the level of tuberculin hypersensitivity. Spleen cells were harvested from the three groups of mice at increasing time intervals and filtered through nylon wool to remove adherent cells, and the level of blast transformation after exposure to phytohemagglutinin and purified protein derivative was determined. Early in the BCG infection both the high- and the intermediate-dose groups showed enhanced thymidine incorporation by the spleen cell cultures, followed by a profound depression late in the infection. At this time, both groups of mice were anergic to purified protein derivative injected into footpads. Cell mixing studies demonstrated the presence of a population of suppressor cells in the spleens of the anergic animals. The suppressive abilities of these cells would be ablated by treatment with anti-Thy-1 antiserum and complement. The aerogenically infected mice were unresponsive to purified protein derivative but showed no evidence of suppressor T-cells. The lack of tuberculin sensitivity in these mice seemed to be due to a lack of sensitized T-cells in the spleen rather than to active immunosuppression."} {"id": "PMID:158568", "title": "Development of suppressor T-cells in Mycobacterium habana-infected mice.", "content": "Mice were infected intravenously with increasing numbers of Mycobacterium habana (simiae serotype II), and the levels of delayed-type hypersensitivity to purified protein derivative and M. habana cytoplasmic protein antigen were determined after 14, 30, and 90 days. A footpad delayed-type hypersensitivity response was seen in 14-day-infected mice and was followed by a persisting anergy. T-cell-enriched suspensions collected 30 and 90 days into the infection (anergic donors) showed depressed transformation indexes after phytohemagglutinin and M. habana cytoplasmic protein antigen treatment in vitro. The corresponding B-cell mitogen (lipopolysaccharide) responses were not affected. Mixing experiments with T-cell-enriched suspensions from day-90 M. habana-infected donors adoptively suppressed lymphocyte transformation by normal and day-14 spleen cells. This effect could be ablated by anti-theta serum and complement treatment of the day-90 cells, indicating that the lack of in vitro responsiveness to cytoplasmic protein antigen was mediated by a population of suppressor T-cells present in the heavily infected spleens. There was no evidence that similar cells were present in the spleens of the 14-day-infected animals. Suppressor T-cells could be induced in vitro by exposure of day-14 spleen cells to concanavalin A or M. habana cytoplasmic protein antigen before they were mixed with normal or day-14 indicator splenic lymphocytes. The timing of the appearance of suppressor T-cells in the infected spleens corresponded to a loss of footpad hypersensitivity by the M. habana-infected animals.", "contents": "Development of suppressor T-cells in Mycobacterium habana-infected mice. Mice were infected intravenously with increasing numbers of Mycobacterium habana (simiae serotype II), and the levels of delayed-type hypersensitivity to purified protein derivative and M. habana cytoplasmic protein antigen were determined after 14, 30, and 90 days. A footpad delayed-type hypersensitivity response was seen in 14-day-infected mice and was followed by a persisting anergy. T-cell-enriched suspensions collected 30 and 90 days into the infection (anergic donors) showed depressed transformation indexes after phytohemagglutinin and M. habana cytoplasmic protein antigen treatment in vitro. The corresponding B-cell mitogen (lipopolysaccharide) responses were not affected. Mixing experiments with T-cell-enriched suspensions from day-90 M. habana-infected donors adoptively suppressed lymphocyte transformation by normal and day-14 spleen cells. This effect could be ablated by anti-theta serum and complement treatment of the day-90 cells, indicating that the lack of in vitro responsiveness to cytoplasmic protein antigen was mediated by a population of suppressor T-cells present in the heavily infected spleens. There was no evidence that similar cells were present in the spleens of the 14-day-infected animals. Suppressor T-cells could be induced in vitro by exposure of day-14 spleen cells to concanavalin A or M. habana cytoplasmic protein antigen before they were mixed with normal or day-14 indicator splenic lymphocytes. The timing of the appearance of suppressor T-cells in the infected spleens corresponded to a loss of footpad hypersensitivity by the M. habana-infected animals."} {"id": "PMID:158571", "title": "A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic.", "content": "A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of Lys-20). The NCS-polystyrene (SMANCS) was purified on a column of Sephadex G-100 in 0.05 M ammonium bicarbonate and the main product was obtained as a single peak. The elemental analysis showed an increased C and a decreased N content. U.v. and i.r. absorption spectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular weight of about 25 000, indicating the numbers of polymers conjugated to be about six units, two of which were found attached to the two amino groups. SMANCS was soluble in organic solvents, in contrast to NCS, and in water. SMANCS exhibited increased chemical and biological stability and appeared to possess similar in vitro biological activity.", "contents": "A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of Lys-20). The NCS-polystyrene (SMANCS) was purified on a column of Sephadex G-100 in 0.05 M ammonium bicarbonate and the main product was obtained as a single peak. The elemental analysis showed an increased C and a decreased N content. U.v. and i.r. absorption spectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular weight of about 25 000, indicating the numbers of polymers conjugated to be about six units, two of which were found attached to the two amino groups. SMANCS was soluble in organic solvents, in contrast to NCS, and in water. SMANCS exhibited increased chemical and biological stability and appeared to possess similar in vitro biological activity."} {"id": "PMID:158572", "title": "Serotonergic mediation of reward within the medial raphe nucleus: some persistent problems in interpretation.", "content": "Adult male Sprague Dawley rats were implanted with unipolar stimulating electrodes aimed at the medial forebrain bundle (MFB) or the medial raphe nucleus (MR). All MFB implanted subjects self-stimulated at high stable rates for at least three weeks. Only a minority (1/3) of MR rats self-stimulated at all. Rates for the MR group were considerably more variable, and could not be maintained for more than two weeks. Treatment with methysergide increased MFB self-stimulation but decreased MR self-stimulation. While this result suggests serotonergic mediation of self-stimulation this conclusion must be interpreted cautiously since parachlorophenylalanine (PCPA) reinstated self-stimulation in raphe animals which had spontaneously ceased responding.", "contents": "Serotonergic mediation of reward within the medial raphe nucleus: some persistent problems in interpretation. Adult male Sprague Dawley rats were implanted with unipolar stimulating electrodes aimed at the medial forebrain bundle (MFB) or the medial raphe nucleus (MR). All MFB implanted subjects self-stimulated at high stable rates for at least three weeks. Only a minority (1/3) of MR rats self-stimulated at all. Rates for the MR group were considerably more variable, and could not be maintained for more than two weeks. Treatment with methysergide increased MFB self-stimulation but decreased MR self-stimulation. While this result suggests serotonergic mediation of self-stimulation this conclusion must be interpreted cautiously since parachlorophenylalanine (PCPA) reinstated self-stimulation in raphe animals which had spontaneously ceased responding."} {"id": "PMID:158569", "title": "Benzoyl peroxide gel therapy in acne in Singapore.", "content": "The results of an open clinical trial of 200 patients in Singapore show that benzoyl peroxide, in a stable gel formulation, both in 2.5% and 5% strengths, was highly efficacious in the topical treatment of acne vulgaris without concomitant systemic therapy. The series included a small number of Caucasians (13 patients) who were also treated effectively. Side effects noted were generally mild and transient.", "contents": "Benzoyl peroxide gel therapy in acne in Singapore. The results of an open clinical trial of 200 patients in Singapore show that benzoyl peroxide, in a stable gel formulation, both in 2.5% and 5% strengths, was highly efficacious in the topical treatment of acne vulgaris without concomitant systemic therapy. The series included a small number of Caucasians (13 patients) who were also treated effectively. Side effects noted were generally mild and transient."} {"id": "PMID:158570", "title": "The combined use of topical benzoyl peroxide and tretinoin in the treatment of acne vulgaris.", "content": "A clinical trial using tretinoin lotion 0.05%, benzoyl peroxide 5% and 10% as topical application was performed on 250 ambulatory patients suffering from various degrees of acne vulgaris. The results indicate that tretinoin applied in the morning and benzoyl peroxide applied at night is the most efficacious regimen to be used, with minimal side effects.", "contents": "The combined use of topical benzoyl peroxide and tretinoin in the treatment of acne vulgaris. A clinical trial using tretinoin lotion 0.05%, benzoyl peroxide 5% and 10% as topical application was performed on 250 ambulatory patients suffering from various degrees of acne vulgaris. The results indicate that tretinoin applied in the morning and benzoyl peroxide applied at night is the most efficacious regimen to be used, with minimal side effects."} {"id": "PMID:158578", "title": "Providing a less restrictive environment for profoundly retarded persons by teaching independent walking skills.", "content": "A basic right of all handicapped persons is to live in the least restrictive environment possible. In this investigation, procedures were evaluated for teaching four institutionalized males with profound retardation necessary skills to increase their individual freedom of movement. Following baseline, a travel training program with a backward chaining format was implemented to teach each person to walk independently from his living area to school. Travel training included instructions, practice, praise, feedback, verbal reprimands, prompts, and edible reinforcers. Each resident began walking the entire distance to school independently during training and also began walking back to the living area, although the latter set of skills was not specifically trained. Following termination of the formal investigation, follow-up measures of 1 to 8 weeks showed the residents continued going to school independently. A survey of residential facilities in 43 states provided social validation for the seriousness of the problems associated with transporting seriously retarded persons to school. Also, time efficiency measures indicated that training independent travel resulted in reductions of staff time required in school transportation. Results were discussed in light of the potential contributions of behavior analysis in providing less restrictive environments for seriously handicapped persons.", "contents": "Providing a less restrictive environment for profoundly retarded persons by teaching independent walking skills. A basic right of all handicapped persons is to live in the least restrictive environment possible. In this investigation, procedures were evaluated for teaching four institutionalized males with profound retardation necessary skills to increase their individual freedom of movement. Following baseline, a travel training program with a backward chaining format was implemented to teach each person to walk independently from his living area to school. Travel training included instructions, practice, praise, feedback, verbal reprimands, prompts, and edible reinforcers. Each resident began walking the entire distance to school independently during training and also began walking back to the living area, although the latter set of skills was not specifically trained. Following termination of the formal investigation, follow-up measures of 1 to 8 weeks showed the residents continued going to school independently. A survey of residential facilities in 43 states provided social validation for the seriousness of the problems associated with transporting seriously retarded persons to school. Also, time efficiency measures indicated that training independent travel resulted in reductions of staff time required in school transportation. Results were discussed in light of the potential contributions of behavior analysis in providing less restrictive environments for seriously handicapped persons."} {"id": "PMID:158575", "title": "The application of pattern recognition techniques in the analysis of metacarpophalangeal lengths.", "content": "Pattern recognition techniques have been applied to the analysis of metacarpophalangeal lengths obtained from hand radiographs. A data base consisting of healthy subjects, and subjects exhibiting achondroplasia, Down's syndrome, and Turner's syndrome was studied. A classification technique was found which effectively separates these conditions. The technique is suitable for computer automation.", "contents": "The application of pattern recognition techniques in the analysis of metacarpophalangeal lengths. Pattern recognition techniques have been applied to the analysis of metacarpophalangeal lengths obtained from hand radiographs. A data base consisting of healthy subjects, and subjects exhibiting achondroplasia, Down's syndrome, and Turner's syndrome was studied. A classification technique was found which effectively separates these conditions. The technique is suitable for computer automation."} {"id": "PMID:158576", "title": "A conformational model of the action of general anesthetics at the membrane level. III. Anesthetics and the properties of membrane-bound enzymes: mitochondrial ATPase.", "content": "We have studied the effect of general anesthetics on the kinetic properties of the mitochondrial Mg2+-dependent ATPase. The enzyme is inhibited by anesthetics (alcohols, halotane, pentrane, ketamine) at concentrations of the order of those found to affect lipid-protein interactions. The inhibition appears usually uncompetitive with respect to the substrate, ATP, with a decrease of both Vmax and KM, indicating a possible stabilization of the enzyme-substrate complex. Arrhenius plots of ATPase activity show a striking increase in activation energy below 17-20 degrees C. Anesthetics affect the temperature dependence by increasing the activation energy above the break or abolishing the break whatsoever. An exception is diethyl ether, that induces a decrease in activation energy and a shift of the break to lower temperatures. Anesthetics make the ATPase insensitive to energy transfer inhibitor, oligomycin and dicyclohexyl carbodiimide. At low anesthetic concentration the oligomycin inhibition curve is changed from sigmoidal to hyperbolic, showing a loss of cooperativity in the inhibition.", "contents": "A conformational model of the action of general anesthetics at the membrane level. III. Anesthetics and the properties of membrane-bound enzymes: mitochondrial ATPase. We have studied the effect of general anesthetics on the kinetic properties of the mitochondrial Mg2+-dependent ATPase. The enzyme is inhibited by anesthetics (alcohols, halotane, pentrane, ketamine) at concentrations of the order of those found to affect lipid-protein interactions. The inhibition appears usually uncompetitive with respect to the substrate, ATP, with a decrease of both Vmax and KM, indicating a possible stabilization of the enzyme-substrate complex. Arrhenius plots of ATPase activity show a striking increase in activation energy below 17-20 degrees C. Anesthetics affect the temperature dependence by increasing the activation energy above the break or abolishing the break whatsoever. An exception is diethyl ether, that induces a decrease in activation energy and a shift of the break to lower temperatures. Anesthetics make the ATPase insensitive to energy transfer inhibitor, oligomycin and dicyclohexyl carbodiimide. At low anesthetic concentration the oligomycin inhibition curve is changed from sigmoidal to hyperbolic, showing a loss of cooperativity in the inhibition."} {"id": "PMID:158588", "title": "Role of polymeric forms of the bacteriophage phi X174 coded gene A protein in phi XRFI DNA cleavage.", "content": "Gene A of the phi X174 genome codes for two proteins, A and A* (Linney, E.A., and Hayashi, M.N. (1973) Nature New Biol. 245, 6-8) of molecular weights 60,000 and 35,000, respectively. The phi X A* protein is formed from a natural internal initiator site within the A gene cistron while the phi X A protein is the product of the entire A gene. These two proteins have been purified to homogeneity as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Previous studies have shown that the phi X A protein is an endonuclease which specifically introduces a discontinuity in the A cistron of the viral strand of supertwisted phi XRFI DNA. In addition to this activity, the phi X A protein also causes relaxation of supertwisted phi XRFI DNA and formation of a phi XRFH DNA . phi X A protein complex which has a discontinuity in the A cistron of the viral strand. This isolatable complex supports DNA synthesis when supplemented with extracts of uninfected Escherichia coli which lack phi X A protein and phi XRFI DNA. The phi XRFII DNA . phi X A protein complex can be attacked by exonuclease III but is not susceptible to attack by E. coli DNA polymerase I, indicating that the 5'-end of the complex is blocked. Attempts to seal the RFII structure generated from the phi XRFII DNA . phi X A protein complex with T4 DNA ligase in the presence or absence of DNA polymerase were unsuccessful. The phi X A protein does not act catalytically in the cleavage of phi XRFI DNA. Under conditions leading to the quantitative cleavage of phi XRFI DNA, the molar ratio of phi XRFI DNA to added phi X A protein was approximately 1:10. At this molar ratio, cross-linking experiments with dimethyl suberimidate yielded 10 distinct protein bands which were multiples of the monomeric phi X A protein. In the absence of DNA or in the presence of inactive DNA (phi XRFII DNA) no distinct protein bands above a trimer were detected. We found it possible in vitro to form a phi XRFII DNA . phi X A protein complex with wild-type phi XRFI DNA (phi X A gene+) and with phi XRFI DNA isolated from E. coli (su+) infected with phage phi X H90 (an am mutant in the phi X A gene). Thus, in vitro, in contrast to in vivo studies, phi X A protein is not a cis acting protein. The purified phi X A* protein does not substitute for the phi X A protein in in vitro replication of phi XRFI DNA nor does it interfere with the action of the phi X A protein which binds only to supertwisted phi XRFI DNA. In contrast, the phi X A* protein binds to all duplex DNA preparations tested. This property prevents nucleases of E. coli from hydrolyzing duplex DNAs to small molecular weight products.", "contents": "Role of polymeric forms of the bacteriophage phi X174 coded gene A protein in phi XRFI DNA cleavage. Gene A of the phi X174 genome codes for two proteins, A and A* (Linney, E.A., and Hayashi, M.N. (1973) Nature New Biol. 245, 6-8) of molecular weights 60,000 and 35,000, respectively. The phi X A* protein is formed from a natural internal initiator site within the A gene cistron while the phi X A protein is the product of the entire A gene. These two proteins have been purified to homogeneity as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Previous studies have shown that the phi X A protein is an endonuclease which specifically introduces a discontinuity in the A cistron of the viral strand of supertwisted phi XRFI DNA. In addition to this activity, the phi X A protein also causes relaxation of supertwisted phi XRFI DNA and formation of a phi XRFH DNA . phi X A protein complex which has a discontinuity in the A cistron of the viral strand. This isolatable complex supports DNA synthesis when supplemented with extracts of uninfected Escherichia coli which lack phi X A protein and phi XRFI DNA. The phi XRFII DNA . phi X A protein complex can be attacked by exonuclease III but is not susceptible to attack by E. coli DNA polymerase I, indicating that the 5'-end of the complex is blocked. Attempts to seal the RFII structure generated from the phi XRFII DNA . phi X A protein complex with T4 DNA ligase in the presence or absence of DNA polymerase were unsuccessful. The phi X A protein does not act catalytically in the cleavage of phi XRFI DNA. Under conditions leading to the quantitative cleavage of phi XRFI DNA, the molar ratio of phi XRFI DNA to added phi X A protein was approximately 1:10. At this molar ratio, cross-linking experiments with dimethyl suberimidate yielded 10 distinct protein bands which were multiples of the monomeric phi X A protein. In the absence of DNA or in the presence of inactive DNA (phi XRFII DNA) no distinct protein bands above a trimer were detected. We found it possible in vitro to form a phi XRFII DNA . phi X A protein complex with wild-type phi XRFI DNA (phi X A gene+) and with phi XRFI DNA isolated from E. coli (su+) infected with phage phi X H90 (an am mutant in the phi X A gene). Thus, in vitro, in contrast to in vivo studies, phi X A protein is not a cis acting protein. The purified phi X A* protein does not substitute for the phi X A protein in in vitro replication of phi XRFI DNA nor does it interfere with the action of the phi X A protein which binds only to supertwisted phi XRFI DNA. In contrast, the phi X A* protein binds to all duplex DNA preparations tested. This property prevents nucleases of E. coli from hydrolyzing duplex DNAs to small molecular weight products."} {"id": "PMID:158593", "title": "Substrate regulation of the sarcoplasmic reticulum ATPase. Transient kinetic studies.", "content": "The rate of phosphorylation of the Ca2+-dependent ATPase of sarcoplasmic reticulum vesicles by ITP and ATP was studied using a millisecond mixing and quenching device. The rate of phosphorylation was slower when the vesicles were preincubated in a Ca2+-free medium than when preincubated with Ca2+, regardless of the substrate used and of the pH of the medium. When the vesicles were preincubated with Ca2+ at pH 7.4 an overshoot of phosphorylation was observed in the presence of ITP. The overshoot was abolished when the pH of the medium was decreased to 6.0 or when the vesicles were preincubated in a Ca2+-free medium. Using vesicles preincubated with Ca2+ the apparent Km for ITP found was 2.5 mM at pH 6.0 and 1.0 mM at pH 7.4. The Vmax observed (77 mumol g-1 s-1) did not change with the pH of the medium. Both at pH 6.0 and 7.4 the apparent Km for ATP was 3 microM when preincubated in a Ca2+-free medium. At pH 6.0 the Vmax for ATP varied from 96 to 33 mumol g-1 s-1 depending on whether the vesicles were preincubated in the presence or absence of Ca2+. At pH 7.4 the Vmax for ATP was 90 mumol g-1 s-1 in both conditions. The rate of phosphorylation of the vesicles was dependent on the relative Ca2+ and Mg2+ concentrations of the reaction medium regardless of the substrate used.", "contents": "Substrate regulation of the sarcoplasmic reticulum ATPase. Transient kinetic studies. The rate of phosphorylation of the Ca2+-dependent ATPase of sarcoplasmic reticulum vesicles by ITP and ATP was studied using a millisecond mixing and quenching device. The rate of phosphorylation was slower when the vesicles were preincubated in a Ca2+-free medium than when preincubated with Ca2+, regardless of the substrate used and of the pH of the medium. When the vesicles were preincubated with Ca2+ at pH 7.4 an overshoot of phosphorylation was observed in the presence of ITP. The overshoot was abolished when the pH of the medium was decreased to 6.0 or when the vesicles were preincubated in a Ca2+-free medium. Using vesicles preincubated with Ca2+ the apparent Km for ITP found was 2.5 mM at pH 6.0 and 1.0 mM at pH 7.4. The Vmax observed (77 mumol g-1 s-1) did not change with the pH of the medium. Both at pH 6.0 and 7.4 the apparent Km for ATP was 3 microM when preincubated in a Ca2+-free medium. At pH 6.0 the Vmax for ATP varied from 96 to 33 mumol g-1 s-1 depending on whether the vesicles were preincubated in the presence or absence of Ca2+. At pH 7.4 the Vmax for ATP was 90 mumol g-1 s-1 in both conditions. The rate of phosphorylation of the vesicles was dependent on the relative Ca2+ and Mg2+ concentrations of the reaction medium regardless of the substrate used."} {"id": "PMID:158595", "title": "Purification of the (Ca2+-Mg2+)-ATPase from human erythrocyte membranes using a calmodulin affinity column.", "content": "The (Ca2+-Mg2+)-ATPase from human erythrocyte membranes has been solubilized in Triton X-100 and purified on a calmodulin affinity chromatography column in the presence of phosphatidylserine, to limit the inactivation of the enzyme. The enzyme was purified at least 150 times when compared with the original ghosts and showed a specific activity of 3.8 mumol.mg-1.min-1. In sodium dodecyl sulfate-polyacrylamide gels, a single major band was visible at a position corresponding to a molecular weight of about 125,000; a minor band (11% of the total protein) was present at a position corresponding to Mr = 205,000. Upon incubation of the purified preparation with [32P]ATP, both bands were phosphorylated in proportion to their mass, suggesting that both were active forms of purified ATPase.", "contents": "Purification of the (Ca2+-Mg2+)-ATPase from human erythrocyte membranes using a calmodulin affinity column. The (Ca2+-Mg2+)-ATPase from human erythrocyte membranes has been solubilized in Triton X-100 and purified on a calmodulin affinity chromatography column in the presence of phosphatidylserine, to limit the inactivation of the enzyme. The enzyme was purified at least 150 times when compared with the original ghosts and showed a specific activity of 3.8 mumol.mg-1.min-1. In sodium dodecyl sulfate-polyacrylamide gels, a single major band was visible at a position corresponding to a molecular weight of about 125,000; a minor band (11% of the total protein) was present at a position corresponding to Mr = 205,000. Upon incubation of the purified preparation with [32P]ATP, both bands were phosphorylated in proportion to their mass, suggesting that both were active forms of purified ATPase."} {"id": "PMID:158596", "title": "Subunit interaction during catalysis. Alternating site cooperativity of mitochondrial adenosine triphosphatase.", "content": "ATP concentration modulates oxygen exchange catalyzed by purified, soluble mitochondrial ATPase during ATP hydrolysis so that water oxygen incorporation into each Pi formed increases markedly as ATP concentration is lowered. This behavior is readily explained by catalytic cooperativity between subunits of the ATPase. However, other reasonable explanations also need consideration. A new approach for assessing these various explanations is used, based on measurement of the [18O]Pi species formed by hydrolysis of ATP highly labeled with 18O in the gamma-phosphoryl group. The results and other supporting data give what appears to be the most compelling evidence yet attained for alternating site catalytic cooperativity in an enzymic catalysis.", "contents": "Subunit interaction during catalysis. Alternating site cooperativity of mitochondrial adenosine triphosphatase. ATP concentration modulates oxygen exchange catalyzed by purified, soluble mitochondrial ATPase during ATP hydrolysis so that water oxygen incorporation into each Pi formed increases markedly as ATP concentration is lowered. This behavior is readily explained by catalytic cooperativity between subunits of the ATPase. However, other reasonable explanations also need consideration. A new approach for assessing these various explanations is used, based on measurement of the [18O]Pi species formed by hydrolysis of ATP highly labeled with 18O in the gamma-phosphoryl group. The results and other supporting data give what appears to be the most compelling evidence yet attained for alternating site catalytic cooperativity in an enzymic catalysis."} {"id": "PMID:158597", "title": "The impact of musculoskeletal disorders on the population of the United States.", "content": "Musculoskeletal disorders constitute such a large component of impairments of individuals in the working and geriatric population that good statistical data on them are essential for planning health care. We have collected the pertinent data, with references to recent source material, to determine the incidence, effect on the quality of life, and associated costs of these disorders in the United States.", "contents": "The impact of musculoskeletal disorders on the population of the United States. Musculoskeletal disorders constitute such a large component of impairments of individuals in the working and geriatric population that good statistical data on them are essential for planning health care. We have collected the pertinent data, with references to recent source material, to determine the incidence, effect on the quality of life, and associated costs of these disorders in the United States."} {"id": "PMID:158600", "title": "Phage heterogeneity of coagulase-negative staphylococci isolated in the United States and Sweden from bovine milk.", "content": "A Swedish bovine and a Dutch human phage set for coagulase-negative staphylococci were used to phage type coagulase-negative staphylococci isolated from bovine milk from Minnesota dairy herds. A comparison was also made of the deoxyribonuclease activity of coagulase-negative staphylococci isolated from bovine milk in Sweden and Minnesota. Of 133 Minnesota isolates, only one could be typed with the Swedish set and one by the Dutch set, whereas of 218 Swedish strains, 49 could be typed with the Swedish set and 7 by the Dutch set. A larger number of coagulase-negative isolates from Sweden were deoxyribonuclease positive (35%) than were the similar isolates from Minnesota (12%). These findings substantiate the marked heterogeneity of coagulase-negative staphylococci isolated from bovine udders. Results presented point to the usefulness of establishing regional phage sets for epidemiological investigations of coagulase-negative staphylococci in cattle. It is anticipated that at a later stage the regional phage sets will be coordinated internationally.", "contents": "Phage heterogeneity of coagulase-negative staphylococci isolated in the United States and Sweden from bovine milk. A Swedish bovine and a Dutch human phage set for coagulase-negative staphylococci were used to phage type coagulase-negative staphylococci isolated from bovine milk from Minnesota dairy herds. A comparison was also made of the deoxyribonuclease activity of coagulase-negative staphylococci isolated from bovine milk in Sweden and Minnesota. Of 133 Minnesota isolates, only one could be typed with the Swedish set and one by the Dutch set, whereas of 218 Swedish strains, 49 could be typed with the Swedish set and 7 by the Dutch set. A larger number of coagulase-negative isolates from Sweden were deoxyribonuclease positive (35%) than were the similar isolates from Minnesota (12%). These findings substantiate the marked heterogeneity of coagulase-negative staphylococci isolated from bovine udders. Results presented point to the usefulness of establishing regional phage sets for epidemiological investigations of coagulase-negative staphylococci in cattle. It is anticipated that at a later stage the regional phage sets will be coordinated internationally."} {"id": "PMID:158602", "title": "The impact of chronic pain on the self-concept.", "content": "Compared self-concepts of three groups, medical patients, chronic low back pain patients and chronic head pain patients (N = 60) to determine (1) whether chronic pain patients have self-perceptions that differ from other medical patients; (2) whether changes in self-perception are limited to physical attributes and capacities; and finally (3) whether persons who suffer different types of chronic pain would have differing self-concepts. Significantly lower self-concepts were obtained from groups of head pain and low back pain patients. Self-concept patterns for the two pain groups were quite similar with the exception of two self-concept components that were significantly lower for the head pain group. Differences were explained in terms of loss of many normal functions and disruption of normal life-styles. Implications for treatment of pain patients and for training of health professionals were discussed.", "contents": "The impact of chronic pain on the self-concept. Compared self-concepts of three groups, medical patients, chronic low back pain patients and chronic head pain patients (N = 60) to determine (1) whether chronic pain patients have self-perceptions that differ from other medical patients; (2) whether changes in self-perception are limited to physical attributes and capacities; and finally (3) whether persons who suffer different types of chronic pain would have differing self-concepts. Significantly lower self-concepts were obtained from groups of head pain and low back pain patients. Self-concept patterns for the two pain groups were quite similar with the exception of two self-concept components that were significantly lower for the head pain group. Differences were explained in terms of loss of many normal functions and disruption of normal life-styles. Implications for treatment of pain patients and for training of health professionals were discussed."} {"id": "PMID:158601", "title": "Bacteriophage typing of coagulase-negative staphylococci.", "content": "Cultures comprising the 10 species of coagulase-negative staphylococci proposed by Kloos and Schleifer (J. Clin. Microbiol. 1:82--88, 1975) were typed with bacteriophages isolated from Staphylococcus epidermidis. Although only 10.5% were typable, 50% of those identified as S. epidermidis were typed. Cultures from patients with middle ear infections were also classified by this system and phage typed.", "contents": "Bacteriophage typing of coagulase-negative staphylococci. Cultures comprising the 10 species of coagulase-negative staphylococci proposed by Kloos and Schleifer (J. Clin. Microbiol. 1:82--88, 1975) were typed with bacteriophages isolated from Staphylococcus epidermidis. Although only 10.5% were typable, 50% of those identified as S. epidermidis were typed. Cultures from patients with middle ear infections were also classified by this system and phage typed."} {"id": "PMID:158598", "title": "[The interstitial pregnancy. Report of three observations (author's transl)].", "content": "The recent occurrence at the Port-Royal obstetrics and gynaecology center of three cases of interstitial pregnancy out of a total number of 208 ectopic pregnancies give us the opportunity to discuss the diagnosis and present management of the rarest form of tubal pregnancies. The diagnosis is always difficult. Nowadays, thanks to the use of echography and especially of laparoscopy, interstitial pregnancies can be detected earlier. Thus the precocity of the diagnosis should permit a conservative surgical treatment. Hysterectomy should not be considered but in very special cases.", "contents": "[The interstitial pregnancy. Report of three observations (author's transl)]. The recent occurrence at the Port-Royal obstetrics and gynaecology center of three cases of interstitial pregnancy out of a total number of 208 ectopic pregnancies give us the opportunity to discuss the diagnosis and present management of the rarest form of tubal pregnancies. The diagnosis is always difficult. Nowadays, thanks to the use of echography and especially of laparoscopy, interstitial pregnancies can be detected earlier. Thus the precocity of the diagnosis should permit a conservative surgical treatment. Hysterectomy should not be considered but in very special cases."} {"id": "PMID:158605", "title": "Adrenal and gonadal steroids and pituitary response to LHRH in girls. I. Delayed puberty.", "content": "Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone (DHA), dehydroepiandrosterone-sulphate (DHA-S), 17-hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) were measured in basal conditions in eleven young women from 16 to 25 years of age characterized by delayed puberty. The gonadotropin response to LHRH (50 microgram iv) was also tested in these cases. The results, as far as gonadotropins and E2 are concerned, indicate that delayed pubertyin girls is a heterogeneous disorder: an impairment in the negative feedback between E2 and FSH coexists with a reduced ovarian response to endogenous gonadotropins. All cases showed evidence of a more or less pronounced delayed adrenarche, which was demonstrated by the markedly reduced levels of DHA-S and DHA (with the exception of this latter steroid in two cases with idiopathic hirsutism). Furthermore, the very low plasma progesterone (P) levels in all cases suggest the existence of impaired delta 5 - delta 4 isomerase activity in the adrenal cells. Despite the low levels of A and T, DHT is within the upper limits of the normal range in all cases.", "contents": "Adrenal and gonadal steroids and pituitary response to LHRH in girls. I. Delayed puberty. Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone (DHA), dehydroepiandrosterone-sulphate (DHA-S), 17-hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) were measured in basal conditions in eleven young women from 16 to 25 years of age characterized by delayed puberty. The gonadotropin response to LHRH (50 microgram iv) was also tested in these cases. The results, as far as gonadotropins and E2 are concerned, indicate that delayed pubertyin girls is a heterogeneous disorder: an impairment in the negative feedback between E2 and FSH coexists with a reduced ovarian response to endogenous gonadotropins. All cases showed evidence of a more or less pronounced delayed adrenarche, which was demonstrated by the markedly reduced levels of DHA-S and DHA (with the exception of this latter steroid in two cases with idiopathic hirsutism). Furthermore, the very low plasma progesterone (P) levels in all cases suggest the existence of impaired delta 5 - delta 4 isomerase activity in the adrenal cells. Despite the low levels of A and T, DHT is within the upper limits of the normal range in all cases."} {"id": "PMID:158608", "title": "Rehabilitating the severely disabled: the foreign experience.", "content": "This paper sets forth a model for examining the relationships between fourteen policy and politicoeconomic variables, and the social benefits and costs of rehabilitation. Based on discussions in early 1977 with scholars, ministry officials, trade unionists, and politicians in several northwestern European countries, as well as on documentation relating to the rapid growth of disability expenditures and the factors thought to influence it, some \"lessons\" are presented for policymakers in the United States and other countries. In general, current trends are seen as depressing the post-service earnings of individual rehabilitants, limiting the stabilizing effects of rehabilitation on labor market turnover, and increasing available time for unpaid work in the home and elsewhere. Unequal intergovernmental cost sharing in the provision of benefits and services, it is argued, seems likely to promote inefficient allocation of scarce rehabilitation resources with negative consequences for goal attainment. The high rates of inflation which prevail in the United States and in many northwestern European countries are causing the immediate costs of providing rehabilitation services to rise and simultaneously increasing the opportunity costs of spending for rehabilitation. The net effect of these cost increases is a reduction in the overall benefit/cost ratio that results from investments in rehabilitation. A number of predictions are made about how the United States will shape its disability and rehabilitation policies in the course of the next twenty years.", "contents": "Rehabilitating the severely disabled: the foreign experience. This paper sets forth a model for examining the relationships between fourteen policy and politicoeconomic variables, and the social benefits and costs of rehabilitation. Based on discussions in early 1977 with scholars, ministry officials, trade unionists, and politicians in several northwestern European countries, as well as on documentation relating to the rapid growth of disability expenditures and the factors thought to influence it, some \"lessons\" are presented for policymakers in the United States and other countries. In general, current trends are seen as depressing the post-service earnings of individual rehabilitants, limiting the stabilizing effects of rehabilitation on labor market turnover, and increasing available time for unpaid work in the home and elsewhere. Unequal intergovernmental cost sharing in the provision of benefits and services, it is argued, seems likely to promote inefficient allocation of scarce rehabilitation resources with negative consequences for goal attainment. The high rates of inflation which prevail in the United States and in many northwestern European countries are causing the immediate costs of providing rehabilitation services to rise and simultaneously increasing the opportunity costs of spending for rehabilitation. The net effect of these cost increases is a reduction in the overall benefit/cost ratio that results from investments in rehabilitation. A number of predictions are made about how the United States will shape its disability and rehabilitation policies in the course of the next twenty years."} {"id": "PMID:158610", "title": "Studies on the effects of ionization on bacterial aerosols in a burns and plastic surgery unit.", "content": "The effect of the ionization of the air on the decay of bacterial aerosols was studied in a Burns and Plastic Surgery Unit. Ions were generated by free corona needles. The air content of bacteria measured by settle plates was found to be smaller during the ionization period than during the controls period. The number of individual phage typed Staph. aureus strains was especially found to be lower during ionization. The opposite potential increased the disappearance of bacteria from the air. The size of skin particles carrying bacteria is not optimum, but the results obtained show that the ionization may have applications in controlling airborne infection.", "contents": "Studies on the effects of ionization on bacterial aerosols in a burns and plastic surgery unit. The effect of the ionization of the air on the decay of bacterial aerosols was studied in a Burns and Plastic Surgery Unit. Ions were generated by free corona needles. The air content of bacteria measured by settle plates was found to be smaller during the ionization period than during the controls period. The number of individual phage typed Staph. aureus strains was especially found to be lower during ionization. The opposite potential increased the disappearance of bacteria from the air. The size of skin particles carrying bacteria is not optimum, but the results obtained show that the ionization may have applications in controlling airborne infection."} {"id": "PMID:158611", "title": "Genetically restricted immune responses in guinea pigs primed in vivo with antigen-bearing macrophages.", "content": "Guinea pigs injected intradermally with antigen pulsed macrophages generate a population of immune T cells that proliferate in vitro on second exposure to antigen. T cells from F1 (2 X 13) guinea pigs immunized with DNP-OVA on one parental macrophage respond in vitro only to DNP-OVA on macrophages identical to those used for immunization and not to DNP-OVA associated with the other parental macrophages. These results demonstrate that the immunogenicity of antigen is dependent upon the macrophages used for priming in that, with this approach, strain 2 or 13 guinea pigs immunized with allogeneic macrophages pulsed with antigen do not respond to either allogeneic or syngeneic antigen-bearing macrophages. However, lysates of antigen-pulsed macrophages can still immunize either allogeneic or syngeneic recipient via their own macrophages. F1 (2 X 13) guinea pigs are immunized by insulin B chain pulsed strain 13 macrophages (responder) but not by strain 2 macrophages (nonresponder) suggesting that whether a F1 (nonresponder X responder) guinea pig recognizes antigen bound to a parental macrophage is genetically restricted before immunization to the same extent as the donor parental macrophages used for immunization.", "contents": "Genetically restricted immune responses in guinea pigs primed in vivo with antigen-bearing macrophages. Guinea pigs injected intradermally with antigen pulsed macrophages generate a population of immune T cells that proliferate in vitro on second exposure to antigen. T cells from F1 (2 X 13) guinea pigs immunized with DNP-OVA on one parental macrophage respond in vitro only to DNP-OVA on macrophages identical to those used for immunization and not to DNP-OVA associated with the other parental macrophages. These results demonstrate that the immunogenicity of antigen is dependent upon the macrophages used for priming in that, with this approach, strain 2 or 13 guinea pigs immunized with allogeneic macrophages pulsed with antigen do not respond to either allogeneic or syngeneic antigen-bearing macrophages. However, lysates of antigen-pulsed macrophages can still immunize either allogeneic or syngeneic recipient via their own macrophages. F1 (2 X 13) guinea pigs are immunized by insulin B chain pulsed strain 13 macrophages (responder) but not by strain 2 macrophages (nonresponder) suggesting that whether a F1 (nonresponder X responder) guinea pig recognizes antigen bound to a parental macrophage is genetically restricted before immunization to the same extent as the donor parental macrophages used for immunization."} {"id": "PMID:158606", "title": "Human placental delta 5-3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase: in vitro effect of dehydroepiandrosterone and allyestrenol.", "content": "The in vitro effects of dehydroepiandrosterone (DHA) and allylestrenol on human placental delta 5- 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity (delta 5-3 beta-HSDH) was investigated by incubation of subcellular fractions with [4-14C] pregnenolone. It has been found that DHA inhibits the delta 5-3 beta-HSDH activity up to -81% at 5 X 10-5 M concentration while allylestrenol seems to be able to lightly stimulate the delt a 5-3 beta-HSDH activity with a maximum effect (+15-26%) at 5 X 10-7 M concentration. The data concerning allylestrenol, seem of particular interest as this compound is used as a progestative drug during pregnancy, if one consider the inhibitory effect exerted by several natural and synthetic steroids on the delta 5-3 beta-HSDH activity.", "contents": "Human placental delta 5-3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase: in vitro effect of dehydroepiandrosterone and allyestrenol. The in vitro effects of dehydroepiandrosterone (DHA) and allylestrenol on human placental delta 5- 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity (delta 5-3 beta-HSDH) was investigated by incubation of subcellular fractions with [4-14C] pregnenolone. It has been found that DHA inhibits the delta 5-3 beta-HSDH activity up to -81% at 5 X 10-5 M concentration while allylestrenol seems to be able to lightly stimulate the delt a 5-3 beta-HSDH activity with a maximum effect (+15-26%) at 5 X 10-7 M concentration. The data concerning allylestrenol, seem of particular interest as this compound is used as a progestative drug during pregnancy, if one consider the inhibitory effect exerted by several natural and synthetic steroids on the delta 5-3 beta-HSDH activity."} {"id": "PMID:158613", "title": "Production of chemotactic activity in mixed leukocyte cultures: maximum effect caused by H-2I region disparity.", "content": "Primary mixed mouse leukocyte culture supernatants contain an activity chemotactic for mouse peritoneal exudate cells and it can be detected within 72 h after initiation of the culture. Disparity for H-21 region leads to maximum production of chemotactic activity whereas H-2K or H-2D region differences result in the production of significantly less activity. The rate of production of chemotactic activity follows closely the rate of incorporation of 3H-thymidine, and both attain the peak on day 4 after initiation of the culture. But whereas proliferation is sensitive to gamma-irradiation, chemotactic activity production is not. It is our hypothesis that proliferating cells are primarily responsible for the production of chemotactic activity. The possible relevance of chemotactic activity production to graft rejection is discussed.", "contents": "Production of chemotactic activity in mixed leukocyte cultures: maximum effect caused by H-2I region disparity. Primary mixed mouse leukocyte culture supernatants contain an activity chemotactic for mouse peritoneal exudate cells and it can be detected within 72 h after initiation of the culture. Disparity for H-21 region leads to maximum production of chemotactic activity whereas H-2K or H-2D region differences result in the production of significantly less activity. The rate of production of chemotactic activity follows closely the rate of incorporation of 3H-thymidine, and both attain the peak on day 4 after initiation of the culture. But whereas proliferation is sensitive to gamma-irradiation, chemotactic activity production is not. It is our hypothesis that proliferating cells are primarily responsible for the production of chemotactic activity. The possible relevance of chemotactic activity production to graft rejection is discussed."} {"id": "PMID:158618", "title": "Competitive nephelometric immunoassay method for antiepileptic drugs in patient blood.", "content": "We established a competitive nephelometric immunoassay method for the determination of the widely used antiepileptic drugs, phenobarbital and diphenylhydantoin, in human blood plasma. The anti-drug antiserum was collected from the immunized rabbit. The human serum albumin possessing numerous drug moieties was easily prepared for the assay reagent. A laser nephelometer was used to measure the scattered light from the immunoprecipitate. The assay was rapid (incubation time 10 min), required as little as 6 microliters of plasma, required neither troublesome pretreatment nor separation procedure. The patients' plasma specimens were analyzed, and the values correlated well to those determined by the high-performance liquid chromatography (correlation coefficient: 0.983 for phenobarbital, 0.987 for diphenylhydantoin).", "contents": "Competitive nephelometric immunoassay method for antiepileptic drugs in patient blood. We established a competitive nephelometric immunoassay method for the determination of the widely used antiepileptic drugs, phenobarbital and diphenylhydantoin, in human blood plasma. The anti-drug antiserum was collected from the immunized rabbit. The human serum albumin possessing numerous drug moieties was easily prepared for the assay reagent. A laser nephelometer was used to measure the scattered light from the immunoprecipitate. The assay was rapid (incubation time 10 min), required as little as 6 microliters of plasma, required neither troublesome pretreatment nor separation procedure. The patients' plasma specimens were analyzed, and the values correlated well to those determined by the high-performance liquid chromatography (correlation coefficient: 0.983 for phenobarbital, 0.987 for diphenylhydantoin)."} {"id": "PMID:158623", "title": "Improved methods for the assay and activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.", "content": "A simple and rapid mixed-phase method for the quantitative assay of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and a procedure for the efficient reactivation of Mg-ATP-inactivated microsomal HMG-CoA reductase by potato acid phosphatase are described. The mixed-phase assay entails the direct addition of the acidified, deproteinized incubation mixture to a toluene-based scintillation fluor. The enzymatic reaction product [3H]-mevalonolactone partitions into the toluene while unreacted 3H-labeled HMG-CoA substrate remains in the aqueous phase and is not detected on scintillation counting. The accuracy and reproducibility of this method are compared to a thin-layer chromatographic assay for HMG-CoA reductase. Microsomal and solubilized HMG-CoA reductase inactivated by incubation with Mg-ATP is reactivated by purified potato acid phosphatase. Under appropriate conditions quantitative reactivation of HMG-CoA reductase is achieved, indicating that endogenous inhibitory and activating proteins regulate HMG-CoA reductase via a kinase-phosphatase system.", "contents": "Improved methods for the assay and activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase. A simple and rapid mixed-phase method for the quantitative assay of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and a procedure for the efficient reactivation of Mg-ATP-inactivated microsomal HMG-CoA reductase by potato acid phosphatase are described. The mixed-phase assay entails the direct addition of the acidified, deproteinized incubation mixture to a toluene-based scintillation fluor. The enzymatic reaction product [3H]-mevalonolactone partitions into the toluene while unreacted 3H-labeled HMG-CoA substrate remains in the aqueous phase and is not detected on scintillation counting. The accuracy and reproducibility of this method are compared to a thin-layer chromatographic assay for HMG-CoA reductase. Microsomal and solubilized HMG-CoA reductase inactivated by incubation with Mg-ATP is reactivated by purified potato acid phosphatase. Under appropriate conditions quantitative reactivation of HMG-CoA reductase is achieved, indicating that endogenous inhibitory and activating proteins regulate HMG-CoA reductase via a kinase-phosphatase system."} {"id": "PMID:158624", "title": "Mechanism of action of fibrinolytic enzymes in vivo.", "content": "Plasminogen-rich and plasminogen-poor radiolabeled human fibrin clots were inserted into large veins of baboons and stump-tailed monkeys. The thrombolytic effects of plasminogen activators (urokinase, streptokinase), and plasmin preparations with activator activity (streptokinase-activated human plasmin) and without activator activity (trypsin-activated porcine plasmin, Lysofibrin) were studied. Plasminogen-free and plasminogen-rich clots lysed at equal rates. Preparations with and without activator activity were equally effective as thrombolytic agents. Endogenous activation of plasminogen in the clot thus appears not to be the essential mechanism of thrombolysis. The exogenous pathway of enzyme adsorption to fibrin fibers seems to represent an important thrombolytic mechanism. Clot lysis was achieved with doses of fibrinolytic enzymes which produced little or no significant hematologic changes including hypofibrinogenemia and decreases of other blood coagulation factor levels.", "contents": "Mechanism of action of fibrinolytic enzymes in vivo. Plasminogen-rich and plasminogen-poor radiolabeled human fibrin clots were inserted into large veins of baboons and stump-tailed monkeys. The thrombolytic effects of plasminogen activators (urokinase, streptokinase), and plasmin preparations with activator activity (streptokinase-activated human plasmin) and without activator activity (trypsin-activated porcine plasmin, Lysofibrin) were studied. Plasminogen-free and plasminogen-rich clots lysed at equal rates. Preparations with and without activator activity were equally effective as thrombolytic agents. Endogenous activation of plasminogen in the clot thus appears not to be the essential mechanism of thrombolysis. The exogenous pathway of enzyme adsorption to fibrin fibers seems to represent an important thrombolytic mechanism. Clot lysis was achieved with doses of fibrinolytic enzymes which produced little or no significant hematologic changes including hypofibrinogenemia and decreases of other blood coagulation factor levels."} {"id": "PMID:158637", "title": "Interaction of glucocorticoid and insulin in the responses of rats to starvation-refeeding.", "content": "Experiments designed to determine whether the role of glucocorticoid (GC) in the induction of the enzyme overshoot response to starvation-refeeding was direct or permissive through insulin were conducted. Intact, adrenalectomized (ADX), and streptozotocin (STREP) treated rats with or without insulin and/or GC replacements were starved for 48 hours and refed a 65% glucose diet for 48 hours. The typical enzyme overshoot response to starvation-refeeding was observed in the intact rats, ADX rats given GC, STREP rats given insulin and ADX-STREP rats given glucocorticoid plus insulin. No overshoot was observed if glucocorticoid was absent whereas a modest increase in enzyme activity could be observed in insulin deficient rats treated with GC.", "contents": "Interaction of glucocorticoid and insulin in the responses of rats to starvation-refeeding. Experiments designed to determine whether the role of glucocorticoid (GC) in the induction of the enzyme overshoot response to starvation-refeeding was direct or permissive through insulin were conducted. Intact, adrenalectomized (ADX), and streptozotocin (STREP) treated rats with or without insulin and/or GC replacements were starved for 48 hours and refed a 65% glucose diet for 48 hours. The typical enzyme overshoot response to starvation-refeeding was observed in the intact rats, ADX rats given GC, STREP rats given insulin and ADX-STREP rats given glucocorticoid plus insulin. No overshoot was observed if glucocorticoid was absent whereas a modest increase in enzyme activity could be observed in insulin deficient rats treated with GC."} {"id": "PMID:158639", "title": "Hypertensive pulmonary vascular disease in Down syndrome.", "content": "Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease.", "contents": "Hypertensive pulmonary vascular disease in Down syndrome. Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease."} {"id": "PMID:158640", "title": "Intrauterine supraventricular tachycardia.", "content": "Six examples of intrauterine supraventricular tachycardia together with 31 previously reported cases are described and analyzed. Among the 37 infants, structural heart disease was present in only four (11%), three of whom died. Males comprised 68% of the group without identifiable heart disease or pre-excitation. Congestive heart failure was evident in 62% of the infants at birth or shortly thereafter; ascites was the predominant finding in three (8%). Neither the duration of SVT nor heart rate was predictive of the clinical status at birth. Infants without underlying heart disease or conduction abnormalities had a benign course after the neonatal period. Thirty-eight percent of the babies converted to sinus rhythm during or shortly after delivery without medication, and most of the others converted after digitalization. The failure of maternal digitalization to convert SVT to sinus rhythm in two of our infants was perhaps related to subtherapeutic maternal and fetal digoxin levels. Newborn infants presenting with unexplained ascites or congestive heart failure should have an ECG to determine whether pre-excitation is present, and their cardiac rhythm should be monitored for several days.", "contents": "Intrauterine supraventricular tachycardia. Six examples of intrauterine supraventricular tachycardia together with 31 previously reported cases are described and analyzed. Among the 37 infants, structural heart disease was present in only four (11%), three of whom died. Males comprised 68% of the group without identifiable heart disease or pre-excitation. Congestive heart failure was evident in 62% of the infants at birth or shortly thereafter; ascites was the predominant finding in three (8%). Neither the duration of SVT nor heart rate was predictive of the clinical status at birth. Infants without underlying heart disease or conduction abnormalities had a benign course after the neonatal period. Thirty-eight percent of the babies converted to sinus rhythm during or shortly after delivery without medication, and most of the others converted after digitalization. The failure of maternal digitalization to convert SVT to sinus rhythm in two of our infants was perhaps related to subtherapeutic maternal and fetal digoxin levels. Newborn infants presenting with unexplained ascites or congestive heart failure should have an ECG to determine whether pre-excitation is present, and their cardiac rhythm should be monitored for several days."} {"id": "PMID:158642", "title": "Effects of gamma-hydroxybutyric acid on metabolic, respiratory and vasomotor activities and body temperature in rats.", "content": "The effects of gamma-hydroxybutyric acid (GHBA) on metabolic, respiratory and vasomotor activities and body temperature were assessed in unanesthetized rats at three different ambient temperatures (Ta) of 8, 22 and 30 degrees C. Intraperitoneal administration of GHBA produced dose-dependent hypothermia in rats at both 8 and 22 degrees C Ta. At Ta = 8 degrees C the hypothermia was brought about solely by a decrease in metabolic heat production, while at Ta = 22 degrees C the hypothermia was due to both a decrease in metabolic heat production and an increase in cutaneous circulation (as indicated by changes in tail and foot skin temperatures). However, at Ta = 30 degrees C GHBA administration produced no changes in rectal temperature or other thermoregulatory parameters. Respiratory evaporative heat loss was not affected by GHBA application. Furthermore, it was found that the GHBA-induced hypothermia was antagonized by haloperidol (a selective blocker of dopamine receptors), but not by p-chlorophenylalanine (an inhibitor of serotonin synthesis). The data suggest that GHBA elicits a central dopamine receptor activation mainly via release of endogenous dopamine and leads to a hypothermia.", "contents": "Effects of gamma-hydroxybutyric acid on metabolic, respiratory and vasomotor activities and body temperature in rats. The effects of gamma-hydroxybutyric acid (GHBA) on metabolic, respiratory and vasomotor activities and body temperature were assessed in unanesthetized rats at three different ambient temperatures (Ta) of 8, 22 and 30 degrees C. Intraperitoneal administration of GHBA produced dose-dependent hypothermia in rats at both 8 and 22 degrees C Ta. At Ta = 8 degrees C the hypothermia was brought about solely by a decrease in metabolic heat production, while at Ta = 22 degrees C the hypothermia was due to both a decrease in metabolic heat production and an increase in cutaneous circulation (as indicated by changes in tail and foot skin temperatures). However, at Ta = 30 degrees C GHBA administration produced no changes in rectal temperature or other thermoregulatory parameters. Respiratory evaporative heat loss was not affected by GHBA application. Furthermore, it was found that the GHBA-induced hypothermia was antagonized by haloperidol (a selective blocker of dopamine receptors), but not by p-chlorophenylalanine (an inhibitor of serotonin synthesis). The data suggest that GHBA elicits a central dopamine receptor activation mainly via release of endogenous dopamine and leads to a hypothermia."} {"id": "PMID:158643", "title": "Tremor in the tension developed isometrically by soleus during the tonic vibration reflex in the decerebrate cat.", "content": "1. Irregularities in the development of tension during the tonic vibration reflex of the soleus muscle of the decerebrate cat have been analysed into their frequency components. The reflex was recorded isometrically and elicited by longitudinal vibration, normally at 150 Hz. The amplitude of vibration was set so as to elicit a maximal reflex response, suggesting 1:1 driving of the majority of the Ia afferents at the frequency of vibration. 2. The resulting power spectrum regularly showed a well marked tremor peak separated by a trough from any slow irregularities. The predominant frequency of this tremor varied from 4 to 11 Hz in different preparations, with a mean of 7.4 Hz; on average, frequencies within 1.7 Hz on either side contained over half the power of the predominant frequency. Altering the frequency of vibration did not alter the distribution of tremor frequencies. 3. The root mean square value of the tension irregularities, over the range 4-14 Hz, varied from 12 to 110 mN in different preparations (median value, 23 mN); this was superimposed on mean active reflex tensions varying from 2 to 10 N. 4. The 'tremor' due to a single motor unit was estimated from spectral analysis of tetanic contractions of the whole muscle and decreased with increasing frequency of activation. Comparison of the single unit values with the tremor seen during vibration in the same preparations showed that equivalent amounts of tremor to the latter could typically have been produced by the continued synchronous contraction of about five 'average' motor units firing at the predominant tremor frequency. 5. When a tonic stretch reflex was present its tremor frequencies did not differ consistently from those of the tonic vibration reflex. On average, the tremor was smaller for the stretch reflex than for the tonic vibration reflex; the difference was usually slight and might have been related to the stretch refex tension being smaller. 6. Evidence was obtained that the tremor was not due to any insecurity of 1:1 driving of the Ia afferents by the vibration. First, the tremor did not increase when the amplitude of vibration was decreased sufficiently to ensure that the degree of 1:1 driving must have been reduced. Secondly, the introduction of a comparable 'artificial tremor' by sinusoidally oscillating the muscle at low frequency did not produce the e.m.g. response that would have been expected if the applied 'tremor' had been modulating the firing of the Ia or any other group of afferents. 7. It is concluded that the observed tremor cannot be attributed to 'oscillation in the stretch reflex arc', though without prejudice to the role of this mechanism under other conditions and especially when the recording is not isometric. However, the genesis of the tremor has not been established and much of it might result simply from the chance synchronization of motor units that are firing below their tetanic fusion frequency.", "contents": "Tremor in the tension developed isometrically by soleus during the tonic vibration reflex in the decerebrate cat. 1. Irregularities in the development of tension during the tonic vibration reflex of the soleus muscle of the decerebrate cat have been analysed into their frequency components. The reflex was recorded isometrically and elicited by longitudinal vibration, normally at 150 Hz. The amplitude of vibration was set so as to elicit a maximal reflex response, suggesting 1:1 driving of the majority of the Ia afferents at the frequency of vibration. 2. The resulting power spectrum regularly showed a well marked tremor peak separated by a trough from any slow irregularities. The predominant frequency of this tremor varied from 4 to 11 Hz in different preparations, with a mean of 7.4 Hz; on average, frequencies within 1.7 Hz on either side contained over half the power of the predominant frequency. Altering the frequency of vibration did not alter the distribution of tremor frequencies. 3. The root mean square value of the tension irregularities, over the range 4-14 Hz, varied from 12 to 110 mN in different preparations (median value, 23 mN); this was superimposed on mean active reflex tensions varying from 2 to 10 N. 4. The 'tremor' due to a single motor unit was estimated from spectral analysis of tetanic contractions of the whole muscle and decreased with increasing frequency of activation. Comparison of the single unit values with the tremor seen during vibration in the same preparations showed that equivalent amounts of tremor to the latter could typically have been produced by the continued synchronous contraction of about five 'average' motor units firing at the predominant tremor frequency. 5. When a tonic stretch reflex was present its tremor frequencies did not differ consistently from those of the tonic vibration reflex. On average, the tremor was smaller for the stretch reflex than for the tonic vibration reflex; the difference was usually slight and might have been related to the stretch refex tension being smaller. 6. Evidence was obtained that the tremor was not due to any insecurity of 1:1 driving of the Ia afferents by the vibration. First, the tremor did not increase when the amplitude of vibration was decreased sufficiently to ensure that the degree of 1:1 driving must have been reduced. Secondly, the introduction of a comparable 'artificial tremor' by sinusoidally oscillating the muscle at low frequency did not produce the e.m.g. response that would have been expected if the applied 'tremor' had been modulating the firing of the Ia or any other group of afferents. 7. It is concluded that the observed tremor cannot be attributed to 'oscillation in the stretch reflex arc', though without prejudice to the role of this mechanism under other conditions and especially when the recording is not isometric. However, the genesis of the tremor has not been established and much of it might result simply from the chance synchronization of motor units that are firing below their tetanic fusion frequency."} {"id": "PMID:158645", "title": "Sterilization of laparoscopes. Is soaking sufficient?", "content": "Controversy exists over the proper methods of sterilizing laparoscopic telescopes. An edict requiring gas sterilization rather than solution soaking of these instruments is in force in all federal hospitals. This rule has necessitated capital investments for new instruments and has led to a severe reduction in the number of cases of laparoscopy that may be scheduled in one day. Fear of contamination is based on theoretical considerations and rusn counter to the actual, observed safety record seen with laparoscopes soaked in activated glutaraldehyde between cases. In an effort to dispassionately approach this problem, cultures of the umbilical area, the laparoscope and the pelvic serosal surfaces were taken to document the type of organisms commonly encountered under clinical conditions. Cultures for aerobic and anaerobic bacteria as well as for fungi were taken after soaking the telescope in activated glutaraldehyde. The results demonstrated growth of common skin organisms even after skin preparation with povidone-iodine and ethyl alcohol. Similar organisms were recovered in some cases from the laparoscope and the pelvic surfaces. The actual degree of contamination suggested by a colony count falls well within the range of the healthy peritoneum to cope with these organisms. Recommendations for laparoscopic sterilization or disinfection are based on the results obtained.", "contents": "Sterilization of laparoscopes. Is soaking sufficient? Controversy exists over the proper methods of sterilizing laparoscopic telescopes. An edict requiring gas sterilization rather than solution soaking of these instruments is in force in all federal hospitals. This rule has necessitated capital investments for new instruments and has led to a severe reduction in the number of cases of laparoscopy that may be scheduled in one day. Fear of contamination is based on theoretical considerations and rusn counter to the actual, observed safety record seen with laparoscopes soaked in activated glutaraldehyde between cases. In an effort to dispassionately approach this problem, cultures of the umbilical area, the laparoscope and the pelvic serosal surfaces were taken to document the type of organisms commonly encountered under clinical conditions. Cultures for aerobic and anaerobic bacteria as well as for fungi were taken after soaking the telescope in activated glutaraldehyde. The results demonstrated growth of common skin organisms even after skin preparation with povidone-iodine and ethyl alcohol. Similar organisms were recovered in some cases from the laparoscope and the pelvic surfaces. The actual degree of contamination suggested by a colony count falls well within the range of the healthy peritoneum to cope with these organisms. Recommendations for laparoscopic sterilization or disinfection are based on the results obtained."} {"id": "PMID:158650", "title": "Lumbar epidural block anesthesia for outpatient laparoscopy.", "content": "This study confirms that lumbar epidural block is a satisfactory anesthetic technique for outpatient laparoscopic tubal sterilization. Oxygenation during the period of pneumoperitoneum was adequate. The technique resulted in a shortened postanesthesia recovery period and fewer postanesthesia complications. Surgeon, anesthesiologist and patient acceptance was excellent.", "contents": "Lumbar epidural block anesthesia for outpatient laparoscopy. This study confirms that lumbar epidural block is a satisfactory anesthetic technique for outpatient laparoscopic tubal sterilization. Oxygenation during the period of pneumoperitoneum was adequate. The technique resulted in a shortened postanesthesia recovery period and fewer postanesthesia complications. Surgeon, anesthesiologist and patient acceptance was excellent."} {"id": "PMID:158651", "title": "Diagnostic miniculdoscopy preceding laparoscopy when bowel adhesions are suspected.", "content": "Suspected bowel adhesions are often considered a relative contraindication to laparoscopy. To attempt preoperative diagnoses of intraabdominal adhesions, miniculdoscopy was performed on ten patients with a miniendoscope. It was possible to establish the presence or absence of adhesions and to determine a safe abdominal trocar insertion site. The laparoscope trocar could be inserted under direct controlled vision with the culdoscope in nine cases, suggesting that this procedure averts bowel adhesions. This technique may be a contribution to safer laparoscopy.", "contents": "Diagnostic miniculdoscopy preceding laparoscopy when bowel adhesions are suspected. Suspected bowel adhesions are often considered a relative contraindication to laparoscopy. To attempt preoperative diagnoses of intraabdominal adhesions, miniculdoscopy was performed on ten patients with a miniendoscope. It was possible to establish the presence or absence of adhesions and to determine a safe abdominal trocar insertion site. The laparoscope trocar could be inserted under direct controlled vision with the culdoscope in nine cases, suggesting that this procedure averts bowel adhesions. This technique may be a contribution to safer laparoscopy."} {"id": "PMID:158653", "title": "Inhibition of lymphocyte responses by gold: modulation by time of drug addition and antigen dose.", "content": "Gold sodium thiomalate added to peripheral blood mononuclear (PBM) cell cultures inhibits the mixed leukocyte reaction (MLR), and cell-mediated cytotoxicity (CMC). The addition of GST to MLR was inhibitory only if the compound was added at the beginning of culture; late addition of GST did not inhibit MLR, or CMC. In a different set of experiments the number of stimulating cells added to MLR was varied. The inhibitory effects of GST decreased markedly as the number of stimulating cells added to culture was increased. The effects of gold in vivo may be modulated by a number of immunologically competent cells that are already antigenically stimulated, as well as by the amount of available stimulating antigen.", "contents": "Inhibition of lymphocyte responses by gold: modulation by time of drug addition and antigen dose. Gold sodium thiomalate added to peripheral blood mononuclear (PBM) cell cultures inhibits the mixed leukocyte reaction (MLR), and cell-mediated cytotoxicity (CMC). The addition of GST to MLR was inhibitory only if the compound was added at the beginning of culture; late addition of GST did not inhibit MLR, or CMC. In a different set of experiments the number of stimulating cells added to MLR was varied. The inhibitory effects of GST decreased markedly as the number of stimulating cells added to culture was increased. The effects of gold in vivo may be modulated by a number of immunologically competent cells that are already antigenically stimulated, as well as by the amount of available stimulating antigen."} {"id": "PMID:158654", "title": "Inhibitory effects of gold and other drugs on mononuclear cell responses: a comparison.", "content": "The effects of gold sodium thiomalate (GST) were compared with those of acetylsalicylic acid (ASA), D-penicillamine (PEN), and methlyprednisolone succinate (MP) on the mixed leukocyte reaction (MLR), and on cell-mediated cytotoxicity (CMC) using mononuclear cells from normal human volunteers. GST and MP inhibited MLR in concentrations readily achieved in the serum, or tissues of patients. ASA showed only a modest effect on MLR, in high concentrations. All drugs inhibited CMC; PEN inhibited CMC at doses of 100 mcg/ml which were no inhibitory in MLR. ASA inhibited CMC at relatively low concentrations. The effects of some of the drugs on MLR and CMC were not consistent. This may be due to the preferential action of the drugs on various immunologically competent cells.", "contents": "Inhibitory effects of gold and other drugs on mononuclear cell responses: a comparison. The effects of gold sodium thiomalate (GST) were compared with those of acetylsalicylic acid (ASA), D-penicillamine (PEN), and methlyprednisolone succinate (MP) on the mixed leukocyte reaction (MLR), and on cell-mediated cytotoxicity (CMC) using mononuclear cells from normal human volunteers. GST and MP inhibited MLR in concentrations readily achieved in the serum, or tissues of patients. ASA showed only a modest effect on MLR, in high concentrations. All drugs inhibited CMC; PEN inhibited CMC at doses of 100 mcg/ml which were no inhibitory in MLR. ASA inhibited CMC at relatively low concentrations. The effects of some of the drugs on MLR and CMC were not consistent. This may be due to the preferential action of the drugs on various immunologically competent cells."} {"id": "PMID:158655", "title": "Effect of gold sodium thiomalate on fibrinolysis.", "content": "Effects of gold sodium thiomalate (GST) on fibrinolytic activities of normal blood and plasma, polymorphonuclear leukocytes (PMN), purified PMN fibrinolytic enzymes, and the enzyme, plasmin, were examined by 125I-fibrin radiometric assay. Of the 2 enzymes accounting for all of the fibrinolytic activity extractable from PMN, the chymotrypsin-like enzyme (cathepsin G),but not the elastase, was inhibited by GST (50% inhibition at 10-6M, 80% inhibition at 10-5M). Plasmin was not inhibited by GST (10-4M to 10-7 M), and these concentrations had no effect on fibrinolytic activities of normal blood and plasma (6 subjects). Activities of PMN preparations from only 2 of 5 normal subjects were inhibited by GST (maximum inhibition of 29% at 10-5 M). These findings indicate a differential effect of GST on PMN elastase and cathepsin G, and suggest a minor role for the latter in normal PMN fibrinolytic activity.", "contents": "Effect of gold sodium thiomalate on fibrinolysis. Effects of gold sodium thiomalate (GST) on fibrinolytic activities of normal blood and plasma, polymorphonuclear leukocytes (PMN), purified PMN fibrinolytic enzymes, and the enzyme, plasmin, were examined by 125I-fibrin radiometric assay. Of the 2 enzymes accounting for all of the fibrinolytic activity extractable from PMN, the chymotrypsin-like enzyme (cathepsin G),but not the elastase, was inhibited by GST (50% inhibition at 10-6M, 80% inhibition at 10-5M). Plasmin was not inhibited by GST (10-4M to 10-7 M), and these concentrations had no effect on fibrinolytic activities of normal blood and plasma (6 subjects). Activities of PMN preparations from only 2 of 5 normal subjects were inhibited by GST (maximum inhibition of 29% at 10-5 M). These findings indicate a differential effect of GST on PMN elastase and cathepsin G, and suggest a minor role for the latter in normal PMN fibrinolytic activity."} {"id": "PMID:158657", "title": "Thyroid replacement therapy in Down's syndrome with hypothyroidism.", "content": "Three elderly subjects with Down's syndrome and biochemical evidence of hypothyroidism were investigated before and after four months of thyroid replacement treatment. The patients' appearance was demonstrated by photographs and the biochemical thyroid values and the intellectual performance were assessed. The appearance before treatment varied from a florid myxoedematous appearance to a state without features indicating myxoedema. Thyroid replacement therapy was given in usual dose and the biochemical response was similar to that seen in normal subjects. The intellectual performance improved little or not at all. The characteristic discomfort usually associated with hypothyroidism was very pronounced in one case and disappeared totally during treatment. It is concluded that the diagnosis of hypothyroidism in elderly subjects with Down's syndrome can be very difficult when based on appearance and history alone and biochemical thyroid tests are often necessary. The patients should be treated with replacement therapy just as other patients suffering from hypothyroidism.", "contents": "Thyroid replacement therapy in Down's syndrome with hypothyroidism. Three elderly subjects with Down's syndrome and biochemical evidence of hypothyroidism were investigated before and after four months of thyroid replacement treatment. The patients' appearance was demonstrated by photographs and the biochemical thyroid values and the intellectual performance were assessed. The appearance before treatment varied from a florid myxoedematous appearance to a state without features indicating myxoedema. Thyroid replacement therapy was given in usual dose and the biochemical response was similar to that seen in normal subjects. The intellectual performance improved little or not at all. The characteristic discomfort usually associated with hypothyroidism was very pronounced in one case and disappeared totally during treatment. It is concluded that the diagnosis of hypothyroidism in elderly subjects with Down's syndrome can be very difficult when based on appearance and history alone and biochemical thyroid tests are often necessary. The patients should be treated with replacement therapy just as other patients suffering from hypothyroidism."} {"id": "PMID:158658", "title": "Blood pressure in Down's syndrome.", "content": "Systolic and diastolic blood pressures of a large sample of subjects with Down's syndrome have been compared with those of institutional controls and of the normal population. Subjects with Down's syndrome have the lowest pressures at all ages and institutional controls tend to fall between the two. The rise of blood pressure with age is slight in the two institutional groups and the reported sex difference in the normal population was not observed.", "contents": "Blood pressure in Down's syndrome. Systolic and diastolic blood pressures of a large sample of subjects with Down's syndrome have been compared with those of institutional controls and of the normal population. Subjects with Down's syndrome have the lowest pressures at all ages and institutional controls tend to fall between the two. The rise of blood pressure with age is slight in the two institutional groups and the reported sex difference in the normal population was not observed."} {"id": "PMID:158659", "title": "Multivariate analyses of the MMPI profiles of low back pain patients.", "content": "A multivariate clustering procedure was used to identify replicable, homogeneous MMPI profile subgroups among three independent cohorts of male (N = 233) and female (N = 315) low back pain ((LBP) patients. Three subgroups were replicated across all male cohorts and four subgroups were replicated across all female cohorts. Multiple discriminant analysis showed that for both male and female patients between-subgroup variability was significantly greater than within-subgroup variability. The results suggest that LBP patients may not be solely characterized by MMPI profiles featuring the \"conversion V\" configuration. Examination of the profile subgroups also suggests there may be distinct, pain-related, behavioral attributes associated with each subgroup which might have important implications for practitioners' choice of treatment modalities. Suggestions are made for research regarding the development of specific, optimal treatments for various LBP patient subgroups.", "contents": "Multivariate analyses of the MMPI profiles of low back pain patients. A multivariate clustering procedure was used to identify replicable, homogeneous MMPI profile subgroups among three independent cohorts of male (N = 233) and female (N = 315) low back pain ((LBP) patients. Three subgroups were replicated across all male cohorts and four subgroups were replicated across all female cohorts. Multiple discriminant analysis showed that for both male and female patients between-subgroup variability was significantly greater than within-subgroup variability. The results suggest that LBP patients may not be solely characterized by MMPI profiles featuring the \"conversion V\" configuration. Examination of the profile subgroups also suggests there may be distinct, pain-related, behavioral attributes associated with each subgroup which might have important implications for practitioners' choice of treatment modalities. Suggestions are made for research regarding the development of specific, optimal treatments for various LBP patient subgroups."} {"id": "PMID:158661", "title": "The blood supply of muscle spindles in some mammals and the pigeon.", "content": "The blood supply of muscle spindles was studied in serial cross sections in macaque, cat, rabbit, guinea pig, mouse and pigeon muscles which had been incubated in a medium containing 3,3' diaminobenzidine. Lumina of blood vessels were recognized by the reaction product that was localized within erythrocytes. The outer capsule was well vascularized, but few or no capillaries were seen in the periaxial space. The inner spindle capsule, which closely invests the axial bundle, was rarely contacted by periaxial capillaries at the equator and juxtequator. Capillaries occurred more frequently adjacent to intrafusal fibers at the polar region and beyond the end of the outer capsule. Shorter diffusion distances and, usually, higher capillary densities were found at the polar region than at the spindle midsection. This suggests that transcapillary exchange at the polar segment is nearer to conditions prevalent in extrafusal muscle than elsewhere in the spindle, provided the inner and outer capsules are not less permeable at the poles than at the midsection. Differences in blood supply among mammalian species appear to be related to receptor size.", "contents": "The blood supply of muscle spindles in some mammals and the pigeon. The blood supply of muscle spindles was studied in serial cross sections in macaque, cat, rabbit, guinea pig, mouse and pigeon muscles which had been incubated in a medium containing 3,3' diaminobenzidine. Lumina of blood vessels were recognized by the reaction product that was localized within erythrocytes. The outer capsule was well vascularized, but few or no capillaries were seen in the periaxial space. The inner spindle capsule, which closely invests the axial bundle, was rarely contacted by periaxial capillaries at the equator and juxtequator. Capillaries occurred more frequently adjacent to intrafusal fibers at the polar region and beyond the end of the outer capsule. Shorter diffusion distances and, usually, higher capillary densities were found at the polar region than at the spindle midsection. This suggests that transcapillary exchange at the polar segment is nearer to conditions prevalent in extrafusal muscle than elsewhere in the spindle, provided the inner and outer capsules are not less permeable at the poles than at the midsection. Differences in blood supply among mammalian species appear to be related to receptor size."} {"id": "PMID:158667", "title": "[An experimental study of nursing work load on the low back (author's transl)].", "content": "The relation between work postures and muscle load, the differences of muscle load in holding two different shaped objects, a human model and a box each weighting 20 kg, and the effects of wearing a belt and a corset to reduce the low back muscle load were studied in the experimental nursing work on physically and/or mentally handicapped patients. Four female healthy college students exercised a static and a dynamic nursing work designed for the experiment. E.M.G., heart rate, subjective symptoms and maximum sustaining time were measured during the work. Results are as follows: 1) The low back muscle load increased only in sustaining the forward bending posture. 2) The forward bending posture with a load weighing 20 kg caused shortening of the time to sustain the same posture. 3) The muscle load by holding the human model was larger compared to that by holding the box, and the muscle load was different according to the shape of the holding objects. 4) Wearing a belt and a corset was effective to reduce the low back muscle load by raising the abdominal pressure.", "contents": "[An experimental study of nursing work load on the low back (author's transl)]. The relation between work postures and muscle load, the differences of muscle load in holding two different shaped objects, a human model and a box each weighting 20 kg, and the effects of wearing a belt and a corset to reduce the low back muscle load were studied in the experimental nursing work on physically and/or mentally handicapped patients. Four female healthy college students exercised a static and a dynamic nursing work designed for the experiment. E.M.G., heart rate, subjective symptoms and maximum sustaining time were measured during the work. Results are as follows: 1) The low back muscle load increased only in sustaining the forward bending posture. 2) The forward bending posture with a load weighing 20 kg caused shortening of the time to sustain the same posture. 3) The muscle load by holding the human model was larger compared to that by holding the box, and the muscle load was different according to the shape of the holding objects. 4) Wearing a belt and a corset was effective to reduce the low back muscle load by raising the abdominal pressure."} {"id": "PMID:158670", "title": "[Correlation of the parameters of myocardial contraction and relaxation in compensatory cardiac hypertrophy].", "content": "The parameters of myocardial contraction and relaxation were determined from the left ventricular pressure curves obtained in closed chest rabbits. One month after the creation of ascending aorta stenosis when the relative weight of the left ventricle increased by 54% as compared to the control, systolic pressure was higher by 42% and maximum rate of pressure development by 47%. This increase corresponded to the degree of left ventricular hypertrophy so that the load on the unit of myocardial mass did not change. No changes were found in the contractility index. The index of relaxation, however, determined by the relation between the maximum rate of relaxation and the developed pressure and characterizing the function of the myocardial relaxation system was 20% lower than that of the control. This was associated with the decrease of the diastolic pause by 27%. The slowing down of relaxation is one of the first and must' signs of compensatory function of the heart.", "contents": "[Correlation of the parameters of myocardial contraction and relaxation in compensatory cardiac hypertrophy]. The parameters of myocardial contraction and relaxation were determined from the left ventricular pressure curves obtained in closed chest rabbits. One month after the creation of ascending aorta stenosis when the relative weight of the left ventricle increased by 54% as compared to the control, systolic pressure was higher by 42% and maximum rate of pressure development by 47%. This increase corresponded to the degree of left ventricular hypertrophy so that the load on the unit of myocardial mass did not change. No changes were found in the contractility index. The index of relaxation, however, determined by the relation between the maximum rate of relaxation and the developed pressure and characterizing the function of the myocardial relaxation system was 20% lower than that of the control. This was associated with the decrease of the diastolic pause by 27%. The slowing down of relaxation is one of the first and must' signs of compensatory function of the heart."} {"id": "PMID:158673", "title": "Transplantation-induced immune complex kidney disease in rats with unilateral manifestation in the allografted kidney.", "content": "Kidney transplantation between major histocompatibility system-identical rat strains LEW.1N (donor) and BN (recipient) is regularly followed by serious immune complex (membranous) glomerulonephritis. The disease localizes in the transplant only and spares the recipient's own contralateral kidney. The recipients develop both circulating immune complexes, as well as circulating antibodies against an allogeneic, tubular epithelial antigen of the donor. Antibodies eluted from the diseased kidneys display the same specificity. The transplant disease, therefore, is not autoimmune glomerulonephritis but an alloimmune, organ-specific illness unrelated to the usual histocompatibility system.", "contents": "Transplantation-induced immune complex kidney disease in rats with unilateral manifestation in the allografted kidney. Kidney transplantation between major histocompatibility system-identical rat strains LEW.1N (donor) and BN (recipient) is regularly followed by serious immune complex (membranous) glomerulonephritis. The disease localizes in the transplant only and spares the recipient's own contralateral kidney. The recipients develop both circulating immune complexes, as well as circulating antibodies against an allogeneic, tubular epithelial antigen of the donor. Antibodies eluted from the diseased kidneys display the same specificity. The transplant disease, therefore, is not autoimmune glomerulonephritis but an alloimmune, organ-specific illness unrelated to the usual histocompatibility system."} {"id": "PMID:158674", "title": "Passive immune complex glomerulonephritis in mice: models for various lesions found in human disease. I. High avidity complexes and mesangiopathic glomerulonephritis.", "content": "Intravenous injection of mice with soluble complexes of highly avid rabbit antibody to egg albumin, prepared by dissolution of equivalence precipitates in large quantities of antigen, resulted in a purely mesangial localization of the complexes. When animals received three injections of complexes per day for 1 day it was noted that precipitates dissolved in 80 times the equivalence amount of antigen produced slight mesangial changes. When such complexes were injected for 2 or 3 days, outright mesangiopathic glomerulonephritis was observed in an increasing proportion of the animals. Equivalent amounts of antigen alone did not produce lesions.", "contents": "Passive immune complex glomerulonephritis in mice: models for various lesions found in human disease. I. High avidity complexes and mesangiopathic glomerulonephritis. Intravenous injection of mice with soluble complexes of highly avid rabbit antibody to egg albumin, prepared by dissolution of equivalence precipitates in large quantities of antigen, resulted in a purely mesangial localization of the complexes. When animals received three injections of complexes per day for 1 day it was noted that precipitates dissolved in 80 times the equivalence amount of antigen produced slight mesangial changes. When such complexes were injected for 2 or 3 days, outright mesangiopathic glomerulonephritis was observed in an increasing proportion of the animals. Equivalent amounts of antigen alone did not produce lesions."} {"id": "PMID:158675", "title": "Passive immune complex glomerulonephritis in mice: models for various lesions found in human disease. II. Low avidity complexes and diffuse proliferative glomerulonephritis with subepithelial deposits.", "content": "Intravenous injections of mice three times a day for 3 days with soluble complexes of 3 mg. of moderately avid rabbit antibody to chicken egg albumin prepared by dissolution of equivalence precipitates in 80 times the equivalence amount of antigen resulted in a combined mesangial and loop localization of immune complexes. With complexes formed from antibody of low avidity, injected four times a day for 3 days, a predominately subepithelial loop deposition of complexes was observed. Complexes formed from moderately avid antibody gave rise to a mainly mesangiopathic glomerulonephritis, whereas low avidity complexes were associated with a diffuse glomerulonephritis. These results, in combination with those of the previous paper, successfully reproduce the basic form of the lesions seen in active immune complex disease by passive means and suggest that antibody avidity is a major determinant of the site of localization of immune complexes and therefore of the morphologic form of the resulting glomerulonephritis. The importance of these observations for our understanding of the pathogenesis of human immune complex disease is considered.", "contents": "Passive immune complex glomerulonephritis in mice: models for various lesions found in human disease. II. Low avidity complexes and diffuse proliferative glomerulonephritis with subepithelial deposits. Intravenous injections of mice three times a day for 3 days with soluble complexes of 3 mg. of moderately avid rabbit antibody to chicken egg albumin prepared by dissolution of equivalence precipitates in 80 times the equivalence amount of antigen resulted in a combined mesangial and loop localization of immune complexes. With complexes formed from antibody of low avidity, injected four times a day for 3 days, a predominately subepithelial loop deposition of complexes was observed. Complexes formed from moderately avid antibody gave rise to a mainly mesangiopathic glomerulonephritis, whereas low avidity complexes were associated with a diffuse glomerulonephritis. These results, in combination with those of the previous paper, successfully reproduce the basic form of the lesions seen in active immune complex disease by passive means and suggest that antibody avidity is a major determinant of the site of localization of immune complexes and therefore of the morphologic form of the resulting glomerulonephritis. The importance of these observations for our understanding of the pathogenesis of human immune complex disease is considered."} {"id": "PMID:158681", "title": "Relationship between steps in 8-anilino-1-naphthalene sulfonate (ANS) fluorescence and changes in the energized membrane state and in intracellular and extracellular adenosine 5'-triphosphate (ATP) levels following bacteriophage T5 infection of Escherichia coli.", "content": "The addition of bacteriophage T5 to anaerobic, fermenting cells of Escherichia coli B or K-12 in the presence of 8-anilino-1-naphthalene sulfonate (ANS), N-phenylnaphthyl-1-amine (NPN), or dansyl ethylamine causes the fluorescence of these probes to rise in two steps, the first occurring immediately upon addition, the second delayed by 6 min. The conditions necessary for observing this phenomenon are defined (cell density, probe concentration, substrate, absence of an electron acceptor, multiplicity of infection, growth, and harvesting conditions). The magnitudes of the first and second steps in fluorescence are dependent upon the multiplicity of infection; the timing of the steps is not. The first step correlates with a breakdown in the potassium or rubidium permeability barrier of the cells, and it occurs either aerobically or anaerobically, with fermentable or nonfermentable substrates. The second step occurs only with cells that are without an available electron acceptor, are fermenting, and which have a functional membrane-bound, Ca2+-dependent adenosine triphosphatase (ATPase). The results are consistent with disturbance of energization of the cell membrane by the membrane-bound ATPase at the time of the second step in fluorescence. No changes in the intracellular level of adenosine 5'-triphosphate (ATP) was seen, whereas the extracellular level increased sharply, starting 3--6 min after phage addition. The quantity of ATP found in the medium by 30 min after infection amounted to about four times the amount present inside the cells at the time of infection. The quantity and rate of efflux of ATP was similar under aerobic and anaerobic conditions.", "contents": "Relationship between steps in 8-anilino-1-naphthalene sulfonate (ANS) fluorescence and changes in the energized membrane state and in intracellular and extracellular adenosine 5'-triphosphate (ATP) levels following bacteriophage T5 infection of Escherichia coli. The addition of bacteriophage T5 to anaerobic, fermenting cells of Escherichia coli B or K-12 in the presence of 8-anilino-1-naphthalene sulfonate (ANS), N-phenylnaphthyl-1-amine (NPN), or dansyl ethylamine causes the fluorescence of these probes to rise in two steps, the first occurring immediately upon addition, the second delayed by 6 min. The conditions necessary for observing this phenomenon are defined (cell density, probe concentration, substrate, absence of an electron acceptor, multiplicity of infection, growth, and harvesting conditions). The magnitudes of the first and second steps in fluorescence are dependent upon the multiplicity of infection; the timing of the steps is not. The first step correlates with a breakdown in the potassium or rubidium permeability barrier of the cells, and it occurs either aerobically or anaerobically, with fermentable or nonfermentable substrates. The second step occurs only with cells that are without an available electron acceptor, are fermenting, and which have a functional membrane-bound, Ca2+-dependent adenosine triphosphatase (ATPase). The results are consistent with disturbance of energization of the cell membrane by the membrane-bound ATPase at the time of the second step in fluorescence. No changes in the intracellular level of adenosine 5'-triphosphate (ATP) was seen, whereas the extracellular level increased sharply, starting 3--6 min after phage addition. The quantity of ATP found in the medium by 30 min after infection amounted to about four times the amount present inside the cells at the time of infection. The quantity and rate of efflux of ATP was similar under aerobic and anaerobic conditions."} {"id": "PMID:158682", "title": "Autologous rectus sheath grafts. V. Growth in aortic grafts.", "content": "Experiments were designed to test autologous rectus sheath as a replacement for the thoracic aorta in the growing dog. Adequacy of graft function was determined by angiography at 4 month intervals; stress-strain measurements and microscopic examination were made at the time of autopsy. A 3 cm tubular graft of rectus sheath tissue was employed as an aortic graft in 13 mongrel puppies. Nine puppies (70%) were long-term survivors and were put to death between 6 and 22 months postoperatively. No deaths were due to graft failure. Angiographic studies demonstrated patency of the graft without development of pressure gradients. An increase in diameter of the aorta (21.25%) and the rectus sheath graft %22.87%) were demonstrated in all cases. During the time of observation, the compliance of the growing aorta (93,120 dynes/cm2) decreased to one fourth that of the control aortic tissue (24,800 dynes/cm2), whereas the compliance of the rectus sheath graft (547,1000 dynes/cm2) decreased to only one eighth that of the control rectus sheath (47,400 dynes/cm2). Tensile strength is maintained in both the growing aorta (4.5 x 10(7) dynes/cm2) and the rectus sheath graft (4.7 x 10(7) dynes/cm2; p less than 0.05). Microscopic examination showed no calcification, thinning, or weakness. Vascularization of the graft had occurred, with cellular proliferation and development of more than 30 lamellar-like units in the media and an adventitia-like surface.", "contents": "Autologous rectus sheath grafts. V. Growth in aortic grafts. Experiments were designed to test autologous rectus sheath as a replacement for the thoracic aorta in the growing dog. Adequacy of graft function was determined by angiography at 4 month intervals; stress-strain measurements and microscopic examination were made at the time of autopsy. A 3 cm tubular graft of rectus sheath tissue was employed as an aortic graft in 13 mongrel puppies. Nine puppies (70%) were long-term survivors and were put to death between 6 and 22 months postoperatively. No deaths were due to graft failure. Angiographic studies demonstrated patency of the graft without development of pressure gradients. An increase in diameter of the aorta (21.25%) and the rectus sheath graft %22.87%) were demonstrated in all cases. During the time of observation, the compliance of the growing aorta (93,120 dynes/cm2) decreased to one fourth that of the control aortic tissue (24,800 dynes/cm2), whereas the compliance of the rectus sheath graft (547,1000 dynes/cm2) decreased to only one eighth that of the control rectus sheath (47,400 dynes/cm2). Tensile strength is maintained in both the growing aorta (4.5 x 10(7) dynes/cm2) and the rectus sheath graft (4.7 x 10(7) dynes/cm2; p less than 0.05). Microscopic examination showed no calcification, thinning, or weakness. Vascularization of the graft had occurred, with cellular proliferation and development of more than 30 lamellar-like units in the media and an adventitia-like surface."} {"id": "PMID:158683", "title": "Effect of cell density and senescence of WI-38 cells on cytochemically demonstrable phosphatases.", "content": "Exponentially growing and stationary phase young and old cultures of the human cell line WI-38 were studied using cytochemistry at the ultrastructural level. 5'-Nucleotidase activity was present in the plasma membrane of all cells examined; in exponentially growing cultures the reaction was more intense in mitotic cells than in interphase cells. An increase in the amount of the reaction product was observed at confluencey, especially in older cells. The reaction of Mg2+-activated adenosine 5'-triphosphatase was absent or very weak in exponentially growing cells and increased at confluency, especially in older cells. Alkaline phosphatase was detectable only in the cell membranes and in intercellular spaces of young cells at confluency. Acid phosphatase activity was increased in old cells, especially at confluency. In these old cells, positive reactions appeared in numerous small lysosomes, autophagic vacuoles and in some flattened sacs of the Golgi apparatus. The obtained results confirm and extend previous biochemical observations and indicate that changes in phosphatase activity are associated with proliferative activity and senescence of cells growing in vitro.", "contents": "Effect of cell density and senescence of WI-38 cells on cytochemically demonstrable phosphatases. Exponentially growing and stationary phase young and old cultures of the human cell line WI-38 were studied using cytochemistry at the ultrastructural level. 5'-Nucleotidase activity was present in the plasma membrane of all cells examined; in exponentially growing cultures the reaction was more intense in mitotic cells than in interphase cells. An increase in the amount of the reaction product was observed at confluencey, especially in older cells. The reaction of Mg2+-activated adenosine 5'-triphosphatase was absent or very weak in exponentially growing cells and increased at confluency, especially in older cells. Alkaline phosphatase was detectable only in the cell membranes and in intercellular spaces of young cells at confluency. Acid phosphatase activity was increased in old cells, especially at confluency. In these old cells, positive reactions appeared in numerous small lysosomes, autophagic vacuoles and in some flattened sacs of the Golgi apparatus. The obtained results confirm and extend previous biochemical observations and indicate that changes in phosphatase activity are associated with proliferative activity and senescence of cells growing in vitro."} {"id": "PMID:158686", "title": "An interpersonal-effectiveness approach to consumer health education: rationale and case study.", "content": "The development and implementation of a program for teaching prospective consumers of medical care services interpersonal-effectiveness advocacy skills are described. Parents of developmentally disabled children attended one of two six-hour workshops to learn self-management, communication and social influence skills for dealing more effectively with health consultants. Consumer satisfaction evaluations indicated that the workshops were successful, and directions for future research and development are discussed.", "contents": "An interpersonal-effectiveness approach to consumer health education: rationale and case study. The development and implementation of a program for teaching prospective consumers of medical care services interpersonal-effectiveness advocacy skills are described. Parents of developmentally disabled children attended one of two six-hour workshops to learn self-management, communication and social influence skills for dealing more effectively with health consultants. Consumer satisfaction evaluations indicated that the workshops were successful, and directions for future research and development are discussed."} {"id": "PMID:158687", "title": "[Portal hypertension in chronic lymphatic leukemia (author's transl)].", "content": "A syndrome of portal hypertension with hemorrhagic ascites was developed in a 44-year-old patient, 2 years after he had been diagnosed as having a chronic lymphatic leukemia. The study of the patient, including two liver biopsies and a laparoscopy, excluded the existence of another hepatic or extrahepatic associated condition. The clinical course of the patient was rapidly fatal progressive in spite of the cytostatic therapy, and he died as a result of an acute liver failure. The autopsy confirmed the absence of vascular occlusions in the suprahepatic veins or in the vena porta. The liver showed, in contrast to the findings of previous biopsies and laparoscopy, an evident fibrotic pattern.", "contents": "[Portal hypertension in chronic lymphatic leukemia (author's transl)]. A syndrome of portal hypertension with hemorrhagic ascites was developed in a 44-year-old patient, 2 years after he had been diagnosed as having a chronic lymphatic leukemia. The study of the patient, including two liver biopsies and a laparoscopy, excluded the existence of another hepatic or extrahepatic associated condition. The clinical course of the patient was rapidly fatal progressive in spite of the cytostatic therapy, and he died as a result of an acute liver failure. The autopsy confirmed the absence of vascular occlusions in the suprahepatic veins or in the vena porta. The liver showed, in contrast to the findings of previous biopsies and laparoscopy, an evident fibrotic pattern."} {"id": "PMID:158694", "title": "Mitochondrial volume density in human skeletal muscle following heavy resistance training.", "content": "Needle biopsies were taken from triceps brachii of 6 healthy males before and after a 6 month intensive weight training programme. The tissue was sectioned, photographed under a Philips EM200 and subjected to stereological analysis. Cross sectional fibre areas were also calculated from cryostat sections stained for ATPase activity. Morphometric analysis indicated that training resulted in a significant 26% reduction in mitochondrial volume density and a 25% reduction in the mitochondrial volume to myofibrillar volume ratio. These changes were accompanied by significant increases in fibre area for both FT (33%) and ST (27%) fibres as determined from the light microscope. There was a significant correlation between the reduction in mitochondrial volume density and the increase in FT fibre area following training (r=0.845). It was concluded that heavy resistance training leads to a dilution of the mitochondrial volume density through an increase in myofibrillar size with hypertrophy.", "contents": "Mitochondrial volume density in human skeletal muscle following heavy resistance training. Needle biopsies were taken from triceps brachii of 6 healthy males before and after a 6 month intensive weight training programme. The tissue was sectioned, photographed under a Philips EM200 and subjected to stereological analysis. Cross sectional fibre areas were also calculated from cryostat sections stained for ATPase activity. Morphometric analysis indicated that training resulted in a significant 26% reduction in mitochondrial volume density and a 25% reduction in the mitochondrial volume to myofibrillar volume ratio. These changes were accompanied by significant increases in fibre area for both FT (33%) and ST (27%) fibres as determined from the light microscope. There was a significant correlation between the reduction in mitochondrial volume density and the increase in FT fibre area following training (r=0.845). It was concluded that heavy resistance training leads to a dilution of the mitochondrial volume density through an increase in myofibrillar size with hypertrophy."} {"id": "PMID:158697", "title": "Streptozotocin-induced diabetes in the spontaneously hypertensive rat.", "content": "Spontaneously hypertensive rats (SHR) were more sensitive to the diabetogenic effects of streptozotocin than normotensive Wistar-Kyoto (WKY) rats. Thus, 10 days after intravenous administration of 25 mg/kg streptozotocin in SHR, mean pancreatic insulin content was decreased by 42% (p less than 0.05), and mean plasma glucose concentration was increased from 85 to 215 mg/dl (p less than 0.001), whereas between 37.5 and 50 mg/kg of streptozotocin was required to produce similar effects in normotensive WKY rats. Also, there was a progressive decrease in blood pressure in SHR injected with 25, 35.7, or 50 mg/kg of streptozotocin, whereas blood pressure was progressively increased after streptozotocin in normotensive WKY rats. The opposite effects of streptozotocin-induced diabetes on blood pressure in SHR and WKY rats could be observed at similar degrees of hyperglycemia and are presently unexplained.", "contents": "Streptozotocin-induced diabetes in the spontaneously hypertensive rat. Spontaneously hypertensive rats (SHR) were more sensitive to the diabetogenic effects of streptozotocin than normotensive Wistar-Kyoto (WKY) rats. Thus, 10 days after intravenous administration of 25 mg/kg streptozotocin in SHR, mean pancreatic insulin content was decreased by 42% (p less than 0.05), and mean plasma glucose concentration was increased from 85 to 215 mg/dl (p less than 0.001), whereas between 37.5 and 50 mg/kg of streptozotocin was required to produce similar effects in normotensive WKY rats. Also, there was a progressive decrease in blood pressure in SHR injected with 25, 35.7, or 50 mg/kg of streptozotocin, whereas blood pressure was progressively increased after streptozotocin in normotensive WKY rats. The opposite effects of streptozotocin-induced diabetes on blood pressure in SHR and WKY rats could be observed at similar degrees of hyperglycemia and are presently unexplained."} {"id": "PMID:158698", "title": "Origin and binding specificity of protein(s) coded for by Mu prophages.", "content": "Crude extracts of bacteria lysogenic for temperature phage Mu contain proteins that retain specifically Mu DNA on nitrocellulose filters. The amount of binding protein is directly proportional to the number of Mu prophages per E. coli genome. Specificity of the binding reaction could be demonstrated by using heterologous DNAs as substrate and by a competition experiment. By using hybrid plasmids containing different amounts of the immunity end and extending to various degrees into MuDNA, it was found that the binding activity is coded for by the left 1,000 nucleotide-pair HindIII fragment. When using these hybrid plasmids as binding substrate, two different binding sites for the immunity product were detected. Joining of the MucI gene to the left lambda early promoter resulted in increased production of immunity protein at elevated temperature. A possible explanation for the relatively low amounts of immunity protein in all of the different strains studied is discussed.", "contents": "Origin and binding specificity of protein(s) coded for by Mu prophages. Crude extracts of bacteria lysogenic for temperature phage Mu contain proteins that retain specifically Mu DNA on nitrocellulose filters. The amount of binding protein is directly proportional to the number of Mu prophages per E. coli genome. Specificity of the binding reaction could be demonstrated by using heterologous DNAs as substrate and by a competition experiment. By using hybrid plasmids containing different amounts of the immunity end and extending to various degrees into MuDNA, it was found that the binding activity is coded for by the left 1,000 nucleotide-pair HindIII fragment. When using these hybrid plasmids as binding substrate, two different binding sites for the immunity product were detected. Joining of the MucI gene to the left lambda early promoter resulted in increased production of immunity protein at elevated temperature. A possible explanation for the relatively low amounts of immunity protein in all of the different strains studied is discussed."} {"id": "PMID:158699", "title": "Spectinomycin-resistant mutants of Bacillus subtilis with altered sporulation properties.", "content": "Spectinomycin-resistant mutants of Bacillus subtilis show three different types of alterations in sporulation ability. Class 1 mutants can both grow and sporulate in the presence of spectinomycin. Class 2 mutants can grow in the presence of spectinomycin, but are unable to sporulate in either the presence or absence of spectinomycin. Class 3 mutants have a conditional phenotype, and are able to sporulate in the absence of spectinomycin, but not in its presence. The ability of these strains to produce alkaline phosphatase, a biochemical marker for early sporulation events, is correlated with the ability to sporulate in the presence or absence of antibiotic. All of the spectinomycin-resistance mutations could be genetically linked to the cysA marker, and a mutational alteration of a protein of the 30S ribosomal subunit has been identified in one of the Class 3 strains (Spc 1-11). Fine-structure mapping of the spectinomycin resistance mutation of strain Spc 1-11 confirmed its location in the cluster of genes for ribosomal components on the B. subtilis genetic map. Genetic analysis indicated that the properties of the Class 1 and Class 2 mutants result from more than one mutation. The spectinomycin-resistance and altered sporulation properties of the two Class 3 mutants probably result from a single genetic lesion.", "contents": "Spectinomycin-resistant mutants of Bacillus subtilis with altered sporulation properties. Spectinomycin-resistant mutants of Bacillus subtilis show three different types of alterations in sporulation ability. Class 1 mutants can both grow and sporulate in the presence of spectinomycin. Class 2 mutants can grow in the presence of spectinomycin, but are unable to sporulate in either the presence or absence of spectinomycin. Class 3 mutants have a conditional phenotype, and are able to sporulate in the absence of spectinomycin, but not in its presence. The ability of these strains to produce alkaline phosphatase, a biochemical marker for early sporulation events, is correlated with the ability to sporulate in the presence or absence of antibiotic. All of the spectinomycin-resistance mutations could be genetically linked to the cysA marker, and a mutational alteration of a protein of the 30S ribosomal subunit has been identified in one of the Class 3 strains (Spc 1-11). Fine-structure mapping of the spectinomycin resistance mutation of strain Spc 1-11 confirmed its location in the cluster of genes for ribosomal components on the B. subtilis genetic map. Genetic analysis indicated that the properties of the Class 1 and Class 2 mutants result from more than one mutation. The spectinomycin-resistance and altered sporulation properties of the two Class 3 mutants probably result from a single genetic lesion."} {"id": "PMID:158700", "title": "Tetrabenazine for involuntary movement disorders.", "content": "The use of tetrabenazine to treat the movement disorder of Huntington's chorea and other dyskinesias is described. Tetrabenazine produced moderate to marked improvement in the movement disorder in 79% of a series of 40 Australian patients. The most commonly reported side effects were depression, drowsiness and Parkinsonism.", "contents": "Tetrabenazine for involuntary movement disorders. The use of tetrabenazine to treat the movement disorder of Huntington's chorea and other dyskinesias is described. Tetrabenazine produced moderate to marked improvement in the movement disorder in 79% of a series of 40 Australian patients. The most commonly reported side effects were depression, drowsiness and Parkinsonism."} {"id": "PMID:158695", "title": "[Peritoneal tuberculosis in Africa (author's transl)].", "content": "Peritonel tuberculosis is quite frequent overseas and specially in Africa; as an example, it is about 0,5 p. 100 of the admittances and 13 p. 100 of the total number of tuberculous cases recorded in Dakar and Djibouti, over a period of four years. First symptoms are not caracteristic but rapidly one may observe either ascitic or non-ascitic forms, with eventually pseudo-tumoral or adhesive aspect. Diagnostic criteria are reviewed as well as the therapeutic rules and results.", "contents": "[Peritoneal tuberculosis in Africa (author's transl)]. Peritonel tuberculosis is quite frequent overseas and specially in Africa; as an example, it is about 0,5 p. 100 of the admittances and 13 p. 100 of the total number of tuberculous cases recorded in Dakar and Djibouti, over a period of four years. First symptoms are not caracteristic but rapidly one may observe either ascitic or non-ascitic forms, with eventually pseudo-tumoral or adhesive aspect. Diagnostic criteria are reviewed as well as the therapeutic rules and results."} {"id": "PMID:158701", "title": "Down's syndrome in South Australia.", "content": "In a survey of Down's syndrome in South Australia, 921 persons, both living and deceased, were identified; 717 individuals with the disorder were living in South Australia. Cytogenetic confirmation of the diagnosis had been made in 774 cases. From 1955 to 1977, the over-all incidence of Down's syndrome at birth was found to be 1.175/1000 live births. The incidence of Down's syndrome was significantly lower over the last five years of this period than for the first 18 years; thus it appears that the incidence of Down's syndrome in South Australia is falling. Analysis of maternal age changes with time has not revealed any changes to the maternal age-specific rates for Down's syndrome, although the rate for mothers aged 25 years or younger appears to be falling. The proportion of Down's syndrome babies born to women aged 35 years or more has decreased from 65.7% for those born before 1950 to 30.4% for those born from 1975 to 1977; similarly, the median maternal age has fallen from 37.12 years to 28.25 years. Regression analyses of maternal age rates for Down's syndrome by single years have produced figures suitable for genetic counselling. A plea is made that Down's syndrome should become a notifiable condition.", "contents": "Down's syndrome in South Australia. In a survey of Down's syndrome in South Australia, 921 persons, both living and deceased, were identified; 717 individuals with the disorder were living in South Australia. Cytogenetic confirmation of the diagnosis had been made in 774 cases. From 1955 to 1977, the over-all incidence of Down's syndrome at birth was found to be 1.175/1000 live births. The incidence of Down's syndrome was significantly lower over the last five years of this period than for the first 18 years; thus it appears that the incidence of Down's syndrome in South Australia is falling. Analysis of maternal age changes with time has not revealed any changes to the maternal age-specific rates for Down's syndrome, although the rate for mothers aged 25 years or younger appears to be falling. The proportion of Down's syndrome babies born to women aged 35 years or more has decreased from 65.7% for those born before 1950 to 30.4% for those born from 1975 to 1977; similarly, the median maternal age has fallen from 37.12 years to 28.25 years. Regression analyses of maternal age rates for Down's syndrome by single years have produced figures suitable for genetic counselling. A plea is made that Down's syndrome should become a notifiable condition."} {"id": "PMID:158702", "title": "Pseudomonas aeruginosa infection depresses contact sensitivity to oxazolone by enhancing suppressor cell activity.", "content": "The depression of contact sensitivity to oxazolone in mice infected with Pseudomonas aeruginosa was studied. In oxazolone-sensitized mice, P. aeruginosa infection affects cell proliferation in the lymph nodes draining the site of sensitization. This impaired cell proliferation does not seem to be due to an altered lymphocyte reactivity, since lymph node and spleen cells from infected animals show a normal mitotic responsiveness to both T and B cell mitogens. In addition, the draining lymph nodes and spleens of mice exhibiting a depressed response to oxazolone contain a cell population able actively to suppress the response to the same antigen of syngeneic recipients sensitized immediately before the cell transfer. These suppressor cells require antigenic stimulation and appear to act on the induction phase of contact sensitivity.", "contents": "Pseudomonas aeruginosa infection depresses contact sensitivity to oxazolone by enhancing suppressor cell activity. The depression of contact sensitivity to oxazolone in mice infected with Pseudomonas aeruginosa was studied. In oxazolone-sensitized mice, P. aeruginosa infection affects cell proliferation in the lymph nodes draining the site of sensitization. This impaired cell proliferation does not seem to be due to an altered lymphocyte reactivity, since lymph node and spleen cells from infected animals show a normal mitotic responsiveness to both T and B cell mitogens. In addition, the draining lymph nodes and spleens of mice exhibiting a depressed response to oxazolone contain a cell population able actively to suppress the response to the same antigen of syngeneic recipients sensitized immediately before the cell transfer. These suppressor cells require antigenic stimulation and appear to act on the induction phase of contact sensitivity."} {"id": "PMID:158703", "title": "Inhibition of interferon action by chinoform.", "content": "Chinoform, iodochlorhydrozyquin, was found to suppress the antiviral action of interferon. Chick embryo fibroblast cells treated with the mixture of interferon and chinoform were more sensitive to Sindbis virus infection than cells treated with interferon alone. No evidence for a direct inactivation of interferon molecule by chinoform was obtained. Treatment with chinoform of cells previously exposed to interferon also removed a cellular antiviral state induced by interferon. Chinoform suppressed intracellular ribonucleic acid (RNA) and protein syntheses. It is suggested that the inhibitory effect of chinoform on the action of interferon is due to a suppression of continued production of antiviral proteins.", "contents": "Inhibition of interferon action by chinoform. Chinoform, iodochlorhydrozyquin, was found to suppress the antiviral action of interferon. Chick embryo fibroblast cells treated with the mixture of interferon and chinoform were more sensitive to Sindbis virus infection than cells treated with interferon alone. No evidence for a direct inactivation of interferon molecule by chinoform was obtained. Treatment with chinoform of cells previously exposed to interferon also removed a cellular antiviral state induced by interferon. Chinoform suppressed intracellular ribonucleic acid (RNA) and protein syntheses. It is suggested that the inhibitory effect of chinoform on the action of interferon is due to a suppression of continued production of antiviral proteins."} {"id": "PMID:158708", "title": "Abnormalities of immunoregulatory T cells in disorders of immune function.", "content": "We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.", "contents": "Abnormalities of immunoregulatory T cells in disorders of immune function. We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man."} {"id": "PMID:158706", "title": "Experimental corticosteroid myopathy: effect on myofibrillar ATPase activity and protein degradation.", "content": "Corticosteroid myopathy was studied in young, mature New Zealand white rabbits given daily injections of betamethasone (0.3 mg/kg body weight/day) for two weeks. Control rabbits were pair-fed and received saline injections. Bethamethasone treatment caused significant wasting of type 2 gluteus medius and psoas muscles but did not cause any atrophy of type 1 soleus and gluteus minimus muscles. The Mg2+- and Ca2+-activated myofibrillar ATPase activities of the corticosteroid-treated rabbits did not differ from controls despite a 30% reduction in muscle wet weight and pronounced reduction in cross-sectional area of fibers. SDS-polyacrylamide gel electrophoresis profiles of myofibrillar proteins did not differ quantitatively or qualitatively between experimental and control rabbits. Studies of net muscle protein degradation (using 3H-leucine) in betamethasone-treated and control rabbits indicate that both type 1 and type 2 muscle fiber proteins are degraded several times faster in the corticosteroid-treated group. This suggests that a compensatory mechanism exists for those type 1 and mixed fiber type muscles which have increased degradation but do not undergo wasting.", "contents": "Experimental corticosteroid myopathy: effect on myofibrillar ATPase activity and protein degradation. Corticosteroid myopathy was studied in young, mature New Zealand white rabbits given daily injections of betamethasone (0.3 mg/kg body weight/day) for two weeks. Control rabbits were pair-fed and received saline injections. Bethamethasone treatment caused significant wasting of type 2 gluteus medius and psoas muscles but did not cause any atrophy of type 1 soleus and gluteus minimus muscles. The Mg2+- and Ca2+-activated myofibrillar ATPase activities of the corticosteroid-treated rabbits did not differ from controls despite a 30% reduction in muscle wet weight and pronounced reduction in cross-sectional area of fibers. SDS-polyacrylamide gel electrophoresis profiles of myofibrillar proteins did not differ quantitatively or qualitatively between experimental and control rabbits. Studies of net muscle protein degradation (using 3H-leucine) in betamethasone-treated and control rabbits indicate that both type 1 and type 2 muscle fiber proteins are degraded several times faster in the corticosteroid-treated group. This suggests that a compensatory mechanism exists for those type 1 and mixed fiber type muscles which have increased degradation but do not undergo wasting."} {"id": "PMID:158710", "title": "Direct addition of insulin inhibits a high affinity Ca2+-ATPase in isolated adipocyte plasma membranes.", "content": "The mechanism by which insulin regulates cellular metabolism remains unknown although indirect evidence suggests that alterations in intracellular calcium are important. More specifically, it has been proposed that insulin triggers an increase in intracellular calcium which is responsible for the subsequent modification of metabolic activities. The cell maintains a large electrochemical gradient for ionised calcium between the cytoplasm (less than 10(-6) M, as determined for muscle and nerve) and the extracellular environment (less than 10(-3) M). The plasma membrane may, therefore, be important in the regulation of calcium homeostasis, as a slight alteration in the processes maintaining this gradient could result in marked changes in cytoplasmic calcium. One such process is the active extrusion of calcium from the cell by a high affinity calcium-stimulated ATPase (Ca2+-ATPase). Such a mechanism has been well established in red cells and is postulated in nerve, liver and muscle. We have identified a high affinity Ca2+-ATPase in a plasma membrane-enriched subcellular fraction isolated from rat adipocytes which may provide the enzymatic basis for a calcium extrusion pump. We demonstrate here that the Ca2+-ATPase is specifically inhibited by the direct addition of physiological concentrations of insulin to the direct addition of physiological concentrations of insulin to the isolated plasma membranes. This effect suggests that direct regulation of calcium homeostasis may represent an important event in the mechanism of action of insulin.", "contents": "Direct addition of insulin inhibits a high affinity Ca2+-ATPase in isolated adipocyte plasma membranes. The mechanism by which insulin regulates cellular metabolism remains unknown although indirect evidence suggests that alterations in intracellular calcium are important. More specifically, it has been proposed that insulin triggers an increase in intracellular calcium which is responsible for the subsequent modification of metabolic activities. The cell maintains a large electrochemical gradient for ionised calcium between the cytoplasm (less than 10(-6) M, as determined for muscle and nerve) and the extracellular environment (less than 10(-3) M). The plasma membrane may, therefore, be important in the regulation of calcium homeostasis, as a slight alteration in the processes maintaining this gradient could result in marked changes in cytoplasmic calcium. One such process is the active extrusion of calcium from the cell by a high affinity calcium-stimulated ATPase (Ca2+-ATPase). Such a mechanism has been well established in red cells and is postulated in nerve, liver and muscle. We have identified a high affinity Ca2+-ATPase in a plasma membrane-enriched subcellular fraction isolated from rat adipocytes which may provide the enzymatic basis for a calcium extrusion pump. We demonstrate here that the Ca2+-ATPase is specifically inhibited by the direct addition of physiological concentrations of insulin to the direct addition of physiological concentrations of insulin to the isolated plasma membranes. This effect suggests that direct regulation of calcium homeostasis may represent an important event in the mechanism of action of insulin."} {"id": "PMID:158711", "title": "The pathology of intrarenal vascular lesions associated with the loin-pain-haematuria syndrome.", "content": "The histological appearances of the proximal and peripheral intrarenal arteries and renal cortex have been examined in 3 patients who underwent nephrectomy for intractable pain associated with the loin-pain-haematuria syndrome. Marked 'atherosclerotic' changes were noted to involve segmental, lobar, interlobar and arcuate arteries with evidence in one kidney of early microaneurysmal formation. These lesions of the more proximal intrarenal arteries were associated with occlusive lesions of the interlobular arteries, areas of cortical ischaemia and cortical infarcts consistent with the changes resulting from microemboli. The histological appearances correlated well with previously described angiographic findings.", "contents": "The pathology of intrarenal vascular lesions associated with the loin-pain-haematuria syndrome. The histological appearances of the proximal and peripheral intrarenal arteries and renal cortex have been examined in 3 patients who underwent nephrectomy for intractable pain associated with the loin-pain-haematuria syndrome. Marked 'atherosclerotic' changes were noted to involve segmental, lobar, interlobar and arcuate arteries with evidence in one kidney of early microaneurysmal formation. These lesions of the more proximal intrarenal arteries were associated with occlusive lesions of the interlobular arteries, areas of cortical ischaemia and cortical infarcts consistent with the changes resulting from microemboli. The histological appearances correlated well with previously described angiographic findings."} {"id": "PMID:158707", "title": "Trichinosis: clinical report and histochemistry of muscle.", "content": "A 35-year-old woman contracted severe trichinosis which was atypical in that it lacked a gastrointestinal prodrome and periorbital edema, and in that eosinophilia developed only late in the course of the illness. The patient developed an incapacitating myositis as well as complications of encephalopathy, myocarditis, and retinal hemorrhages, resulting in severe debilitation of more than two and one-half months' duration. Muscle histochemistry illustrated previously unreported features.", "contents": "Trichinosis: clinical report and histochemistry of muscle. A 35-year-old woman contracted severe trichinosis which was atypical in that it lacked a gastrointestinal prodrome and periorbital edema, and in that eosinophilia developed only late in the course of the illness. The patient developed an incapacitating myositis as well as complications of encephalopathy, myocarditis, and retinal hemorrhages, resulting in severe debilitation of more than two and one-half months' duration. Muscle histochemistry illustrated previously unreported features."} {"id": "PMID:158716", "title": "Relative efficacy of clinical examination, electromyography, plain film radiography, myelography and lumbar phlebography in the diagnosis of low back pain and sciatica.", "content": "The procedures used in the investigation of low back pain and sciatica have been subjected to a double statistical analysis to determine their diagnostic accuracy, since contradictory opinions have been expressed in the literature. It was found that only lumbar phlebography was more accurate than the most simple procedure, the clinical examination. Myelography is more accurate than clinical examination only in making a positive diagnosis. In this case, it equals the reliability of lumbar phlebography, but so does plain film radiography which however leads to a positive diagnosis less constantly. Lumbar phlebography is the most accurate procedure for making a negative diagnosis, mainly by avoiding a false negative conclusion. A comparison is made with the statements in the literature and the complementary use of the different procedures is proposed for the investigation of low back pain and sciatica.", "contents": "Relative efficacy of clinical examination, electromyography, plain film radiography, myelography and lumbar phlebography in the diagnosis of low back pain and sciatica. The procedures used in the investigation of low back pain and sciatica have been subjected to a double statistical analysis to determine their diagnostic accuracy, since contradictory opinions have been expressed in the literature. It was found that only lumbar phlebography was more accurate than the most simple procedure, the clinical examination. Myelography is more accurate than clinical examination only in making a positive diagnosis. In this case, it equals the reliability of lumbar phlebography, but so does plain film radiography which however leads to a positive diagnosis less constantly. Lumbar phlebography is the most accurate procedure for making a negative diagnosis, mainly by avoiding a false negative conclusion. A comparison is made with the statements in the literature and the complementary use of the different procedures is proposed for the investigation of low back pain and sciatica."} {"id": "PMID:158718", "title": "Laparoscopic tubal sterilization using thermal coagulation.", "content": "A technique using a low-voltage, rechargeable battery pack and a cautery hook assembly for thermal coagulation and division of the fallopian tube under laparoscopic visualization has been evaluated in 393 patients. The procedure is quick, easy to perform, and electrically safe. The gross extent of the burn to the fallopian tube by thermal coagulation and division was compared with that done by high-frequency unipolar electrocoagulation and division. The difference in the mean total gross tubal burn produced by the 2 methods is not statistically significant. The variance of total tubal burn in individual cases within each group is significantly greater in the electrocoagulation group. The authors assume that pregnancy rates in patients undergoing thermal coagulation and division will be no different than those reported in patients in the electrocoagulation and division group. Two hundred of the patients have been followed from 12 to 33 months and no method-failure pregnancies have occurred.", "contents": "Laparoscopic tubal sterilization using thermal coagulation. A technique using a low-voltage, rechargeable battery pack and a cautery hook assembly for thermal coagulation and division of the fallopian tube under laparoscopic visualization has been evaluated in 393 patients. The procedure is quick, easy to perform, and electrically safe. The gross extent of the burn to the fallopian tube by thermal coagulation and division was compared with that done by high-frequency unipolar electrocoagulation and division. The difference in the mean total gross tubal burn produced by the 2 methods is not statistically significant. The variance of total tubal burn in individual cases within each group is significantly greater in the electrocoagulation group. The authors assume that pregnancy rates in patients undergoing thermal coagulation and division will be no different than those reported in patients in the electrocoagulation and division group. Two hundred of the patients have been followed from 12 to 33 months and no method-failure pregnancies have occurred."} {"id": "PMID:158735", "title": "A study of the use of electronic environmental control systems by severely paralysed patients.", "content": "The types of environmental control systems issued by the Department of Health and Social Security in England are described. The extent to which the apparatus is used by patients in the north-east Thames region is recorded according to the location (sitting room, bedroom, etc.), the number of hours in use and telephone calls made.", "contents": "A study of the use of electronic environmental control systems by severely paralysed patients. The types of environmental control systems issued by the Department of Health and Social Security in England are described. The extent to which the apparatus is used by patients in the north-east Thames region is recorded according to the location (sitting room, bedroom, etc.), the number of hours in use and telephone calls made."} {"id": "PMID:158736", "title": "Electronic communications and environmental control systems for the severely disabled.", "content": "A wireless environmental controller is described. The controller can either be used by itself or with other systems. It is suggested that commercially available personal computers, for environmental control and communication, will enable the severely disabled to lead a more independent life and may provide useful mental recreation.", "contents": "Electronic communications and environmental control systems for the severely disabled. A wireless environmental controller is described. The controller can either be used by itself or with other systems. It is suggested that commercially available personal computers, for environmental control and communication, will enable the severely disabled to lead a more independent life and may provide useful mental recreation."} {"id": "PMID:158737", "title": "The handicap profile of the spinal cord-damaged in case file, communication documents and population survey.", "content": "\"Definitions\" of handicap are given, with a classification of intrinsic (personal) handicaps, as well as Tables for the preparation of an individual's Handicap Profile, of use in population Surveys and in case files.\"", "contents": "The handicap profile of the spinal cord-damaged in case file, communication documents and population survey. \"Definitions\" of handicap are given, with a classification of intrinsic (personal) handicaps, as well as Tables for the preparation of an individual's Handicap Profile, of use in population Surveys and in case files.\""} {"id": "PMID:158733", "title": "Ossicular abnormalities in Down's syndrome.", "content": "Down's syndrome has been associated with hearing loss and otitis media. Because of difficulty in examination, however, there have been few detailed otologic studies on this population. An understanding of the nature and frequency of ear disease in Down's syndrome is important, since it is common and occurs in more than one in every 600 live births. To define the aural manifestation of Down's syndrome, complete otologic and audiometric examination was performed on 107 consecutive patients. This included micropneumatic otoscopy, pure-tone and speech audiometry, impedance tympanometry, and, in some cases, electronystagmography. Deficient hearing was found in 64% of these patients, and of these hearing losses, 83% were conductive. Surprisingly, middle ear effusion or tympanic membrane perforation accounted for only 60% of the conductive hearing losses. This finding prompted us to examine five temporal bones of children with Down's syndrome. These histologic sections revealed middle ear abnormalities including fixation and superstructure deformity of the stapes and dehiscence of the fallopian canal. Operative findings in 16 procedures on patients with Down's syndrome and conductive hearing loss suport those findings.", "contents": "Ossicular abnormalities in Down's syndrome. Down's syndrome has been associated with hearing loss and otitis media. Because of difficulty in examination, however, there have been few detailed otologic studies on this population. An understanding of the nature and frequency of ear disease in Down's syndrome is important, since it is common and occurs in more than one in every 600 live births. To define the aural manifestation of Down's syndrome, complete otologic and audiometric examination was performed on 107 consecutive patients. This included micropneumatic otoscopy, pure-tone and speech audiometry, impedance tympanometry, and, in some cases, electronystagmography. Deficient hearing was found in 64% of these patients, and of these hearing losses, 83% were conductive. Surprisingly, middle ear effusion or tympanic membrane perforation accounted for only 60% of the conductive hearing losses. This finding prompted us to examine five temporal bones of children with Down's syndrome. These histologic sections revealed middle ear abnormalities including fixation and superstructure deformity of the stapes and dehiscence of the fallopian canal. Operative findings in 16 procedures on patients with Down's syndrome and conductive hearing loss suport those findings."} {"id": "PMID:158743", "title": "[Vasogenic cerebral oedema. Changes in membrane ATPases. Correction by a phospholipid precursor (author's transl)].", "content": "In vasogenic cerebral oedema, there is progressive quantitative and qualitative impairment of mitochondrial ATPase and of Na/K/ATPase. This impairment, which reflects the intracellular component of cerebral oedema, would appear to be related to changes in the phospholipid environment of the cell membrane enzymes. CDP choline, a metabolic phospholipid precursor, is to a certain extent capable of correcting this disturbed activity and at the same time reduce oedema.", "contents": "[Vasogenic cerebral oedema. Changes in membrane ATPases. Correction by a phospholipid precursor (author's transl)]. In vasogenic cerebral oedema, there is progressive quantitative and qualitative impairment of mitochondrial ATPase and of Na/K/ATPase. This impairment, which reflects the intracellular component of cerebral oedema, would appear to be related to changes in the phospholipid environment of the cell membrane enzymes. CDP choline, a metabolic phospholipid precursor, is to a certain extent capable of correcting this disturbed activity and at the same time reduce oedema."} {"id": "PMID:158738", "title": "[New species and new finds of trombiculid mites of the genus Leptotrombidium in Tadzhikistan (Trombiculidae)].", "content": "New species of chiggers from Tadzhikistan are described: Leptotrombidium tamanta sp. n. differs from all other species in having pubescent dorsal and lateral setae on the tibia of palps; L. derlatkoi sp. n. and L. apertum sp. n. are similar with L. smirnovi Kudryashova et Ribin, 1974, from which the former differs in having in the first dorsal row 8 setae instead of 10 and in certain sizes and the latter--in having a smaller number of setae on the body, short barbs on the dorsal setae and sizes. L. solum sp. n. differs from the close species L. europaeum (Daniel et Brelih, 1959) in the number of dorsal setae (43 instead of 34), their location and smaller sizes of the scutum. L. wolandi sp. n. differs from the preceding species by a greater number of NDV and shorter PL. L. multiplex sp. n. is characterized by a great number of setae on the body (104--120). L. smirnovi is first reported from Tadzhikistan.", "contents": "[New species and new finds of trombiculid mites of the genus Leptotrombidium in Tadzhikistan (Trombiculidae)]. New species of chiggers from Tadzhikistan are described: Leptotrombidium tamanta sp. n. differs from all other species in having pubescent dorsal and lateral setae on the tibia of palps; L. derlatkoi sp. n. and L. apertum sp. n. are similar with L. smirnovi Kudryashova et Ribin, 1974, from which the former differs in having in the first dorsal row 8 setae instead of 10 and in certain sizes and the latter--in having a smaller number of setae on the body, short barbs on the dorsal setae and sizes. L. solum sp. n. differs from the close species L. europaeum (Daniel et Brelih, 1959) in the number of dorsal setae (43 instead of 34), their location and smaller sizes of the scutum. L. wolandi sp. n. differs from the preceding species by a greater number of NDV and shorter PL. L. multiplex sp. n. is characterized by a great number of setae on the body (104--120). L. smirnovi is first reported from Tadzhikistan."} {"id": "PMID:158739", "title": "[Number of generations of Xenopsylla skrjabini fleas on the Mangyshlak Peninsula (Aphaniptera)].", "content": "Seasonal changes in the female age composition of micropopulations of X. skrjabini are described. The descriptions are based on observations conducted within a period of 1971-1976. The comparison of females' age with the time of mass egg laying and the data on the developmental cycle rate (from egg to imago) suggests that in Mangyshlak fleas of X. skrjabini have four generations a year. The second, third and fourth generations parasitise at the end of summer or early in autumn. The third and fourth generations hibernate in the quiescence state, begin reproducting in the spring of the next year and in June give start on the first summer generation.", "contents": "[Number of generations of Xenopsylla skrjabini fleas on the Mangyshlak Peninsula (Aphaniptera)]. Seasonal changes in the female age composition of micropopulations of X. skrjabini are described. The descriptions are based on observations conducted within a period of 1971-1976. The comparison of females' age with the time of mass egg laying and the data on the developmental cycle rate (from egg to imago) suggests that in Mangyshlak fleas of X. skrjabini have four generations a year. The second, third and fourth generations parasitise at the end of summer or early in autumn. The third and fourth generations hibernate in the quiescence state, begin reproducting in the spring of the next year and in June give start on the first summer generation."} {"id": "PMID:158744", "title": "[Glomerulopathies during hepatic disease (author's transl)].", "content": "Glomerular lesions essentially characterized by IgA deposits are very frequent in the course of alcoholic hepatopathies. Such glomerular lesions might be due to the deposition of the circulating immune complexes. Portal hypertension, by altering the epuration function of the liver could be one determining factor. The presence of similar glomerular lesions in other non alcoholic hepatopathies with portal hypertension and in experimental portal hypertension support such an hypothesis. In other circumstances where the liver disease is directly related to a viral or a parasitic agent glomerular lesion of the type seen in circulating immune complexes disease are also encountered. However in such a situation there is no evidence that the hepatic disease bears any influence on the renal disease.", "contents": "[Glomerulopathies during hepatic disease (author's transl)]. Glomerular lesions essentially characterized by IgA deposits are very frequent in the course of alcoholic hepatopathies. Such glomerular lesions might be due to the deposition of the circulating immune complexes. Portal hypertension, by altering the epuration function of the liver could be one determining factor. The presence of similar glomerular lesions in other non alcoholic hepatopathies with portal hypertension and in experimental portal hypertension support such an hypothesis. In other circumstances where the liver disease is directly related to a viral or a parasitic agent glomerular lesion of the type seen in circulating immune complexes disease are also encountered. However in such a situation there is no evidence that the hepatic disease bears any influence on the renal disease."} {"id": "PMID:158740", "title": "[Ecology and distribution of the tick, Ixodes lividus, in Karelia (Ixodidae)].", "content": "The territory of Karelia was investigated from 62 degrees to 66 degrees N. In the nests of Riparia riparia the tick Ixodes lividus at all active phases of its development was first found. On the northern border of its distribution area the species shows a tendency to hibernate at the phases of nymph, female and male. This ability has favoured to a considerable extent the advancement of the species into the northern latitudes up t degrees 66 degrees N.", "contents": "[Ecology and distribution of the tick, Ixodes lividus, in Karelia (Ixodidae)]. The territory of Karelia was investigated from 62 degrees to 66 degrees N. In the nests of Riparia riparia the tick Ixodes lividus at all active phases of its development was first found. On the northern border of its distribution area the species shows a tendency to hibernate at the phases of nymph, female and male. This ability has favoured to a considerable extent the advancement of the species into the northern latitudes up t degrees 66 degrees N."} {"id": "PMID:158747", "title": "Rapid RNA sequencing: nucleases from Staphylococcus aureus and Neurospora crassa discriminate between uridine and cytidine.", "content": "Using end-labelled RNA, significant changes in base specificity of three nucleases have been detected under defined conditions. Staphylococcus aureus nuclease at pH 3.5 without Ca++ cleaves all Pyr-N bonds more uniformly and efficiently than RNase A, without any preference for Pyr-A bonds. At pH 7.5 in 10 mM Ca++ this enzyme cleaves all N-C and N-G bonds slowly, whereas N-U and N-A bonds are hydrolyzed rapidly. Hence, the base at the 3'- or at the 5'-side of a phosphodiester bond can determine the base specificity of S. aureus nuclease. - In absence of urea, Neurospora crassa endonuclease cleaves all phosphodiester bonds, but leaves all C-N bonds intact in 7 M urea. - RNase U2 at pH 3.5 cleaves A-N bonds more efficiently than at pH 5.0.", "contents": "Rapid RNA sequencing: nucleases from Staphylococcus aureus and Neurospora crassa discriminate between uridine and cytidine. Using end-labelled RNA, significant changes in base specificity of three nucleases have been detected under defined conditions. Staphylococcus aureus nuclease at pH 3.5 without Ca++ cleaves all Pyr-N bonds more uniformly and efficiently than RNase A, without any preference for Pyr-A bonds. At pH 7.5 in 10 mM Ca++ this enzyme cleaves all N-C and N-G bonds slowly, whereas N-U and N-A bonds are hydrolyzed rapidly. Hence, the base at the 3'- or at the 5'-side of a phosphodiester bond can determine the base specificity of S. aureus nuclease. - In absence of urea, Neurospora crassa endonuclease cleaves all phosphodiester bonds, but leaves all C-N bonds intact in 7 M urea. - RNase U2 at pH 3.5 cleaves A-N bonds more efficiently than at pH 5.0."} {"id": "PMID:158748", "title": "Hybridization of synthetic oligodeoxyribonucleotides to phi chi 174 DNA: the effect of single base pair mismatch.", "content": "Oligodeoxyribonucleotides complementary to the DNA of the wild type (wt) bacteriophage phi chi 174 have been synthesized by the phosphotriester method. The oligomers, 11, 14, and 17 bases long, are complementary to the region of the DNA which accounts for the am-3 point mutation. When hybridized to am-3 DNA, the oligonucleotides form duplexes with a single base pair mismatch. The thermal stability of the duplexes formed between wt and am-3 DNAs has been measured. The am-3 DNA:oligomer duplexes dissociate at a temperature about 10 degrees C lower than the corresponding wt DNA:oligomer duplexes. This dramatic decrease in thermal stability due to a single mismatch makes it possible to eliminate the formation of the mismatched duplexes by the appropriate choice of hybridization temperature. These results are discussed with respect to the use of oligonucleotides as probes for the isolation of specific cloned DNA sequences.", "contents": "Hybridization of synthetic oligodeoxyribonucleotides to phi chi 174 DNA: the effect of single base pair mismatch. Oligodeoxyribonucleotides complementary to the DNA of the wild type (wt) bacteriophage phi chi 174 have been synthesized by the phosphotriester method. The oligomers, 11, 14, and 17 bases long, are complementary to the region of the DNA which accounts for the am-3 point mutation. When hybridized to am-3 DNA, the oligonucleotides form duplexes with a single base pair mismatch. The thermal stability of the duplexes formed between wt and am-3 DNAs has been measured. The am-3 DNA:oligomer duplexes dissociate at a temperature about 10 degrees C lower than the corresponding wt DNA:oligomer duplexes. This dramatic decrease in thermal stability due to a single mismatch makes it possible to eliminate the formation of the mismatched duplexes by the appropriate choice of hybridization temperature. These results are discussed with respect to the use of oligonucleotides as probes for the isolation of specific cloned DNA sequences."} {"id": "PMID:158749", "title": "Defined transversion mutations at a specific position in DNA using synthetic oligodeoxyribonucleotides as mutagens.", "content": "The oligodeoxyribonucleotides, pCCCAGCCTCAA, which is complementary to nucleotides 5274--4284 of bacteriophage phi X174 viral DNA , and pCCCAGCCTAAA, which corresponds to the same sequence with a C leads to A change at the ninth nucleotide, were synthesized enzymatically. The second of these oligonucleotides was used as a primer for E. coli DNA polymerase I, from which the 5'-exonculease has been removed by proteolysis (Klenow enzyme), on wild-type phi X174 viral DNA template. After ligation, this yielded closed circular heteroduplex DNA with a G, A mismatch at nucleotide 5276. Transfection of E. coli spheroplasts with the heteroduplex DNA produced phage mutated at this nucleotide (G leads to T in the viral DNA) with high efficiency (13%). The mutant DNA, which corresponds to the gene B mutant am16, was reverted (T leads to G) by the wild type oligonucleotide with an efficiency of 19%. The nucleotide changes were established by sequence determination of the mutated viral DNA using the enzymatic terminator method. The production of specific transversion mutations, together with a previous demonstration of specific transition mutations (1), established that short enzymatically synthesized oligodeoxyribonucleotides can be used to induce any class of single nucleotide replacement with high efficiency and thus provide a powerful tool for specific genetic manipulations in circular genomes like that of phi X174.", "contents": "Defined transversion mutations at a specific position in DNA using synthetic oligodeoxyribonucleotides as mutagens. The oligodeoxyribonucleotides, pCCCAGCCTCAA, which is complementary to nucleotides 5274--4284 of bacteriophage phi X174 viral DNA , and pCCCAGCCTAAA, which corresponds to the same sequence with a C leads to A change at the ninth nucleotide, were synthesized enzymatically. The second of these oligonucleotides was used as a primer for E. coli DNA polymerase I, from which the 5'-exonculease has been removed by proteolysis (Klenow enzyme), on wild-type phi X174 viral DNA template. After ligation, this yielded closed circular heteroduplex DNA with a G, A mismatch at nucleotide 5276. Transfection of E. coli spheroplasts with the heteroduplex DNA produced phage mutated at this nucleotide (G leads to T in the viral DNA) with high efficiency (13%). The mutant DNA, which corresponds to the gene B mutant am16, was reverted (T leads to G) by the wild type oligonucleotide with an efficiency of 19%. The nucleotide changes were established by sequence determination of the mutated viral DNA using the enzymatic terminator method. The production of specific transversion mutations, together with a previous demonstration of specific transition mutations (1), established that short enzymatically synthesized oligodeoxyribonucleotides can be used to induce any class of single nucleotide replacement with high efficiency and thus provide a powerful tool for specific genetic manipulations in circular genomes like that of phi X174."} {"id": "PMID:158752", "title": "Acupuncture analgesia for chronic low back pain.", "content": "Preliminary findings are presented of a double-blind, crossover trial comparing the effects of traditional with placebo acupuncture in relieving chronic low back pain. 77 patients completed the study. Following initial assessment and baseline readings, patients had a 4-week course of active or placebo treatment given twice weekly. After a 4 week rest period patients received the alternate treatment, using the same time schedule. A 4 week follow-up period completed the trial. Using visual analogue scale readings as a measure of pain there was no cumulative difference in pain reduction achieved by traditional as compared with placebo acupuncture treatment. Both groups achieved a 55% overall reduction in pain level at the end of the trial, compared with initial baseline readings.", "contents": "Acupuncture analgesia for chronic low back pain. Preliminary findings are presented of a double-blind, crossover trial comparing the effects of traditional with placebo acupuncture in relieving chronic low back pain. 77 patients completed the study. Following initial assessment and baseline readings, patients had a 4-week course of active or placebo treatment given twice weekly. After a 4 week rest period patients received the alternate treatment, using the same time schedule. A 4 week follow-up period completed the trial. Using visual analogue scale readings as a measure of pain there was no cumulative difference in pain reduction achieved by traditional as compared with placebo acupuncture treatment. Both groups achieved a 55% overall reduction in pain level at the end of the trial, compared with initial baseline readings."} {"id": "PMID:158750", "title": "Effect of chronic administration of antidepressant drugs on the noradrenaline disappearance induced by FLA-63 in the rat brain.", "content": "We evaluated noradrenaline (NA) level and NA disappearance after FLA-63 in some regions of the brain of rats chronically treated with antidepressants: imipramine (IMI), amitriptyline (AMI) and danitracen (DAN). IMI (10 mg/kg sc), AMI (10 mg/kg sc) and DAN (3 mg/kg ip) were administered to rats twice daily for 10 days. Experiments with a single dose of antidepressants were carried out for comparison. Given chronically, IMI decelerated NA disappearance in the cortex after 2, 24, 48 hr but accelerated it 72 hr after the last injection; AMI did not produce any change in the brain regions examined up to 72 hr; DAN accelerated NA disappearance in the cortex and in the limbic system, whereas it effected no changes in the pons+medulla. These results indicate that: 1) the effects of chronic administration of IMI, AMI or DAN on the brain NA disappearance are different, 2) chronic administration of antidepressants produces effects not found at a single administration.", "contents": "Effect of chronic administration of antidepressant drugs on the noradrenaline disappearance induced by FLA-63 in the rat brain. We evaluated noradrenaline (NA) level and NA disappearance after FLA-63 in some regions of the brain of rats chronically treated with antidepressants: imipramine (IMI), amitriptyline (AMI) and danitracen (DAN). IMI (10 mg/kg sc), AMI (10 mg/kg sc) and DAN (3 mg/kg ip) were administered to rats twice daily for 10 days. Experiments with a single dose of antidepressants were carried out for comparison. Given chronically, IMI decelerated NA disappearance in the cortex after 2, 24, 48 hr but accelerated it 72 hr after the last injection; AMI did not produce any change in the brain regions examined up to 72 hr; DAN accelerated NA disappearance in the cortex and in the limbic system, whereas it effected no changes in the pons+medulla. These results indicate that: 1) the effects of chronic administration of IMI, AMI or DAN on the brain NA disappearance are different, 2) chronic administration of antidepressants produces effects not found at a single administration."} {"id": "PMID:158757", "title": "Electron microscopic analysis of transcription: mapping of initiation sites and direction of transcription.", "content": "An electron microscope technique is described that allows rapid characterization of transcription in vitro. DNA is transcribed with Escherichia coli RNA polymerase in vitro, and the RNA is hybridized to its template. Measurement of the resulting transcription R-loop molecules allows accurate mapping of transcription initiation sites (promoter sites) and analysis of the direction and rate of transcription and the level of transcription from each initiation site. The two major early promoters pR and pL of bacteriophage lambda have been mapped within 0.1-0.3 map units of the known positions and three additional sites have been confirmed. Six transcription initiation sites have been preliminarily mapped on plasmid pSF2124 DNA.", "contents": "Electron microscopic analysis of transcription: mapping of initiation sites and direction of transcription. An electron microscope technique is described that allows rapid characterization of transcription in vitro. DNA is transcribed with Escherichia coli RNA polymerase in vitro, and the RNA is hybridized to its template. Measurement of the resulting transcription R-loop molecules allows accurate mapping of transcription initiation sites (promoter sites) and analysis of the direction and rate of transcription and the level of transcription from each initiation site. The two major early promoters pR and pL of bacteriophage lambda have been mapped within 0.1-0.3 map units of the known positions and three additional sites have been confirmed. Six transcription initiation sites have been preliminarily mapped on plasmid pSF2124 DNA."} {"id": "PMID:158758", "title": "The rat serum albumin gene: analysis of cloned sequences.", "content": "The rat serum albumin gene has been isolated from a recombinant library containing the entire rat genome cloned in the lambda phage Charon 4A. Preliminary R-loop and restriction analysis has revealed that this gene is split into at least 14 fragments (exons) by 13 intervening sequences (introns), and that it occupies a minimum of 14.5 kilobases of genomic DNA.", "contents": "The rat serum albumin gene: analysis of cloned sequences. The rat serum albumin gene has been isolated from a recombinant library containing the entire rat genome cloned in the lambda phage Charon 4A. Preliminary R-loop and restriction analysis has revealed that this gene is split into at least 14 fragments (exons) by 13 intervening sequences (introns), and that it occupies a minimum of 14.5 kilobases of genomic DNA."} {"id": "PMID:158759", "title": "Regulation of ribosomal protein synthesis in Escherichia coli by selective mRNA inactivation.", "content": "In an Escherichia coli strain lysogenic for lambda spc2 transducing phage, an extra copy of ribosomal protein (r-protein) genes in the spc and alpha operons are carried on the phage chromosome. Expression of genes in the spc operon in this merodiploid strain was compared with that in a control \"haploid\" strain carrying lambda trkA phage. It was found that the synthesis rate of spc mRNA, relative to other reference mRNA in the merodiploid strain, is about 2-fold higher than that in the control strain; yet, no dosage effect was observed in the synthesis rate of r-proteins in the spc or alpha operon. The spc mRNA was found to be more rapidly degraded in the merodiploid strain than in the control strain, and its steady-state amount, relative to reference mRNA, was only slightly higher in the merodiploid strain than in the control strain. Thus, E. coli cells have the ability to regulate the rate of r-protein synthesis regardless of the rate of transcription of r-protein genes, presumably by inactivation of the mRNA followed by its degradation. A model is proposed which involves selective inactivation of r-protein mRNA by a feedback mechanism. The model can explain coordinated synthesis of r-proteins and other observations related to selective expression of certain alleles in diploid strains.", "contents": "Regulation of ribosomal protein synthesis in Escherichia coli by selective mRNA inactivation. In an Escherichia coli strain lysogenic for lambda spc2 transducing phage, an extra copy of ribosomal protein (r-protein) genes in the spc and alpha operons are carried on the phage chromosome. Expression of genes in the spc operon in this merodiploid strain was compared with that in a control \"haploid\" strain carrying lambda trkA phage. It was found that the synthesis rate of spc mRNA, relative to other reference mRNA in the merodiploid strain, is about 2-fold higher than that in the control strain; yet, no dosage effect was observed in the synthesis rate of r-proteins in the spc or alpha operon. The spc mRNA was found to be more rapidly degraded in the merodiploid strain than in the control strain, and its steady-state amount, relative to reference mRNA, was only slightly higher in the merodiploid strain than in the control strain. Thus, E. coli cells have the ability to regulate the rate of r-protein synthesis regardless of the rate of transcription of r-protein genes, presumably by inactivation of the mRNA followed by its degradation. A model is proposed which involves selective inactivation of r-protein mRNA by a feedback mechanism. The model can explain coordinated synthesis of r-proteins and other observations related to selective expression of certain alleles in diploid strains."} {"id": "PMID:158760", "title": "T lymphocyte response to H-2 mutants: cytotoxic effectors are Ly-1+2+.", "content": "The lymphocyte differentiation (Ly) antigen phenotype of cytotoxic effector T cells specific for H-2 mutant alloantigens was determined. Cytotoxic effectors generated in primary mixed lymphocyte culture and specific for H-2Kba and H-2Dda alloantigens are sensitive to both anti-Ly-1 and anti-Ly-2 serum plus complement. Reconstitution analysis demonstrated that the mutant-specific T cells were Ly-1+2+. These observations and those previously reported, which indicated that H-2K/D mutant-specific T cells proliferating in mixed lymphocyte culture were Ly-1+2+, demonstrated that Ly-1+2+ T cells are immunocompetent. Furthermore, the nature of the stimulating H-2 complex alloantigen determines the Ly phenotype of responsive T cells.", "contents": "T lymphocyte response to H-2 mutants: cytotoxic effectors are Ly-1+2+. The lymphocyte differentiation (Ly) antigen phenotype of cytotoxic effector T cells specific for H-2 mutant alloantigens was determined. Cytotoxic effectors generated in primary mixed lymphocyte culture and specific for H-2Kba and H-2Dda alloantigens are sensitive to both anti-Ly-1 and anti-Ly-2 serum plus complement. Reconstitution analysis demonstrated that the mutant-specific T cells were Ly-1+2+. These observations and those previously reported, which indicated that H-2K/D mutant-specific T cells proliferating in mixed lymphocyte culture were Ly-1+2+, demonstrated that Ly-1+2+ T cells are immunocompetent. Furthermore, the nature of the stimulating H-2 complex alloantigen determines the Ly phenotype of responsive T cells."} {"id": "PMID:158761", "title": "Help and suppression by lymphoid cells as a function of cellular concentration.", "content": "The phytohemagglutinin-stimulated uptake of [3H]thymidine in mixtures of human lymphocytes from the same source was shown to depend on the cell concentration in vitro as well as on the period of cultivation. \"Helper\" and \"suppressor\" effects were obtained by varying the concentration of cells and the periods of cultivation. The possibility that helper and suppressor subpopulations were responsible was avoided by mixing lymphoid cell line cells with others of the same monoclonal origin. Even under these conditions, both the direction and the extent of activity depended on the same two variables. This weakens the case for postulating the existence of distinct subpopulations of lymphocytes with helper or suppressor properties. This case was based on the use of damaging treatments believed to separate cell populations which were then found to differ in their helper and suppressor properties. We propose instead that the effect of such treatments is mediated through changes in the concentrations of interacting cells. Our data make it clear that the function of lymphoid cells ascertained in one set of conditions need not apply within a different cellular environment.", "contents": "Help and suppression by lymphoid cells as a function of cellular concentration. The phytohemagglutinin-stimulated uptake of [3H]thymidine in mixtures of human lymphocytes from the same source was shown to depend on the cell concentration in vitro as well as on the period of cultivation. \"Helper\" and \"suppressor\" effects were obtained by varying the concentration of cells and the periods of cultivation. The possibility that helper and suppressor subpopulations were responsible was avoided by mixing lymphoid cell line cells with others of the same monoclonal origin. Even under these conditions, both the direction and the extent of activity depended on the same two variables. This weakens the case for postulating the existence of distinct subpopulations of lymphocytes with helper or suppressor properties. This case was based on the use of damaging treatments believed to separate cell populations which were then found to differ in their helper and suppressor properties. We propose instead that the effect of such treatments is mediated through changes in the concentrations of interacting cells. Our data make it clear that the function of lymphoid cells ascertained in one set of conditions need not apply within a different cellular environment."} {"id": "PMID:158762", "title": "Reconstitution and purification by \"transport specificity fractionation\" of an ATP-dependent calcium transport component from synaptosome-derived vesicles.", "content": "A synaptosomal ATP-dependent Ca uptake system was reconstituted into artificial vesicles by a cholate dialysis procedure using an 80-fold excess of exogenous phospholipid. Under these conditions, most of these vesicles would be expected to have only one or, at most, a few membrane proteins. The vesicles containing an ATP-dependent Ca transport system were purified from the bulk of the preparation on density gradients by increasing their density by the ATP-dependent intravesicular precipitation of Ca oxalate; a approximately 100-fold purification resulted. The purified Ca-transporting vesicles contained two major protein components, of Mr 94,000 and 140,000 according to sodium dodecyl sulfate gel electrophoresis. These components are believed to be responsible for Ca transport in this synaptosome-derived membrane fraction.", "contents": "Reconstitution and purification by \"transport specificity fractionation\" of an ATP-dependent calcium transport component from synaptosome-derived vesicles. A synaptosomal ATP-dependent Ca uptake system was reconstituted into artificial vesicles by a cholate dialysis procedure using an 80-fold excess of exogenous phospholipid. Under these conditions, most of these vesicles would be expected to have only one or, at most, a few membrane proteins. The vesicles containing an ATP-dependent Ca transport system were purified from the bulk of the preparation on density gradients by increasing their density by the ATP-dependent intravesicular precipitation of Ca oxalate; a approximately 100-fold purification resulted. The purified Ca-transporting vesicles contained two major protein components, of Mr 94,000 and 140,000 according to sodium dodecyl sulfate gel electrophoresis. These components are believed to be responsible for Ca transport in this synaptosome-derived membrane fraction."} {"id": "PMID:158763", "title": "Rotational motion and evidence for oligomeric structures of sarcoplasmic reticulum Ca2+-activated ATPase.", "content": "The rotational motion of the sarcoplasmic reticulum Ca2+-activated ATPase (ATP phosphohydrolase, EC 3.6.1.3) has been investigated by measuring the decay of laser flash-induced dichroism with the covalently attached triplet probe eosin isothiocyanate. The Arrhenius plot for rotational mobility indicates two discontinuities at approximately 15 degrees C and approximately 35 degrees C. The experimental data are rationalized in terms of a sudden conformeric change in the ATPase at 15 degrees C and a temperature-dependent equilibrium existing between the conformationally altered ATPase and oligomeric forms of it in the temperature range 15-35 degrees C. The enzymatic activity, as indicated by a discontinuity in the Arrhenius plot for the rate of ATP hydrolysis, appears to be sensitive only to the change at 15 degrees C. There is a strong correlation between the activation energy below 15 degrees C for rotational motion (33.6 +/- 2.2 kcal/mol) and enzymatic activity (34 +/- 4 kcal/mol).", "contents": "Rotational motion and evidence for oligomeric structures of sarcoplasmic reticulum Ca2+-activated ATPase. The rotational motion of the sarcoplasmic reticulum Ca2+-activated ATPase (ATP phosphohydrolase, EC 3.6.1.3) has been investigated by measuring the decay of laser flash-induced dichroism with the covalently attached triplet probe eosin isothiocyanate. The Arrhenius plot for rotational mobility indicates two discontinuities at approximately 15 degrees C and approximately 35 degrees C. The experimental data are rationalized in terms of a sudden conformeric change in the ATPase at 15 degrees C and a temperature-dependent equilibrium existing between the conformationally altered ATPase and oligomeric forms of it in the temperature range 15-35 degrees C. The enzymatic activity, as indicated by a discontinuity in the Arrhenius plot for the rate of ATP hydrolysis, appears to be sensitive only to the change at 15 degrees C. There is a strong correlation between the activation energy below 15 degrees C for rotational motion (33.6 +/- 2.2 kcal/mol) and enzymatic activity (34 +/- 4 kcal/mol)."} {"id": "PMID:158764", "title": "Trophoblast modulation of maternal allogeneic recognition.", "content": "Human syncytiotrophoblast cell membranes prepared by differential ultracentrifugation were extracted with 3 M KCl, solubilized in 1% deoxycholate, and chromatographically separated into two peaks by passage through a column of Bio-Gel P-200. Previous reports from this laboratory have shown that the first peak (PI) is serologically the same as a group of trophoblast membrane antigens tentatively designated as TA1. Microgram amounts of P1 protein were found to completely inhibit the mixed lymphocyte culture (MLC) reaction but had no suppressive effect on lymphocyte responses to the lectins phytohemagglutinin or pokeweed mitogen. Control P1 membrane fractions identically prepared from human erythrocytes and liver powder had no inhibitory effects on either MLC reactions or lymphocyte responses to mitogens. Dose response experiments with P1 from 10 different placentae showed total inhibition of MLC by all preparations when used between 25 and 50 microgram/0.2-ml MLC mixture, but some P1 fractions inhibited significantly at much lower concentrations. Timed experiments revealed that MLC suppression was maximal when P1 was added within 12 hr after culture initiation and that no effect could be found with addition after 48 hr. We have previously shown that TA1 is a lymphocyte product of allogeneic responses, and the present results indicate that P1 proteins are themselves involved in the biology of lymphocyte responses to allogeneic cells. Pregnancy is one of the few natural circumstances in which a mixing of allogeneic cells occurs in vivo, and the presence of P1 proteins at the operational interface in the host-parasite relationship of human pregnancy suggests that this trophoblast membrane constituent is involved in the modulation of maternal allogeneic responses.", "contents": "Trophoblast modulation of maternal allogeneic recognition. Human syncytiotrophoblast cell membranes prepared by differential ultracentrifugation were extracted with 3 M KCl, solubilized in 1% deoxycholate, and chromatographically separated into two peaks by passage through a column of Bio-Gel P-200. Previous reports from this laboratory have shown that the first peak (PI) is serologically the same as a group of trophoblast membrane antigens tentatively designated as TA1. Microgram amounts of P1 protein were found to completely inhibit the mixed lymphocyte culture (MLC) reaction but had no suppressive effect on lymphocyte responses to the lectins phytohemagglutinin or pokeweed mitogen. Control P1 membrane fractions identically prepared from human erythrocytes and liver powder had no inhibitory effects on either MLC reactions or lymphocyte responses to mitogens. Dose response experiments with P1 from 10 different placentae showed total inhibition of MLC by all preparations when used between 25 and 50 microgram/0.2-ml MLC mixture, but some P1 fractions inhibited significantly at much lower concentrations. Timed experiments revealed that MLC suppression was maximal when P1 was added within 12 hr after culture initiation and that no effect could be found with addition after 48 hr. We have previously shown that TA1 is a lymphocyte product of allogeneic responses, and the present results indicate that P1 proteins are themselves involved in the biology of lymphocyte responses to allogeneic cells. Pregnancy is one of the few natural circumstances in which a mixing of allogeneic cells occurs in vivo, and the presence of P1 proteins at the operational interface in the host-parasite relationship of human pregnancy suggests that this trophoblast membrane constituent is involved in the modulation of maternal allogeneic responses."} {"id": "PMID:158765", "title": "Effects of serotonin content on pain sensitivity in the rat.", "content": "In this study the role of serotonin in pain sensitivity was investigated. Brain serotonin was elevated via low and high doses of precursor tryptophan and lowered via parachlorophenylalanine or lesions placed in the dorsal raphe nucleus. The effects on pain sensitivity were then assessed using two psychophysical pain testing procedures: (1) minimum shock intensity (threshold) which produced a conditioned escape response; and (2) total activity elicited by highly aversive inescapable shock. The results showed that only a large elevation of serotonin produced a change in escape thresholds in the direction of hypoalgesia. When total activity to a painful inescapable stimulus was evaluated only lowering of serotonin produced an effect, and this change was in the direction of hyperalgesia. The conclusion was made that serotonin does contribute to the mechanism of pain.", "contents": "Effects of serotonin content on pain sensitivity in the rat. In this study the role of serotonin in pain sensitivity was investigated. Brain serotonin was elevated via low and high doses of precursor tryptophan and lowered via parachlorophenylalanine or lesions placed in the dorsal raphe nucleus. The effects on pain sensitivity were then assessed using two psychophysical pain testing procedures: (1) minimum shock intensity (threshold) which produced a conditioned escape response; and (2) total activity elicited by highly aversive inescapable shock. The results showed that only a large elevation of serotonin produced a change in escape thresholds in the direction of hypoalgesia. When total activity to a painful inescapable stimulus was evaluated only lowering of serotonin produced an effect, and this change was in the direction of hyperalgesia. The conclusion was made that serotonin does contribute to the mechanism of pain."} {"id": "PMID:158766", "title": "Pargyline and tryptophan enhancement of tonic immobility: paradoxical attenuation with combined administration.", "content": "Four experiments were conducted to examine the individual and combined effects of pargyline and tryptophan on the duration of tonic immobility in chickens. Injection of either compound alone produced a dose-dependent potentiation of tonic immobility. However, combined administration of pargyline and tryptophan resulted in a dramatic attenuation of the response and this effect was completely blocked by pretreatment with p-chlorophenylalanine. In addition to reducing the duration of tonic immobility, combined administration of pargyline and tryptophan produced a complex behavioral syndrome which may be analogous to that observed in mammals after similar drug treatment. These results suggest the need for a modification of the recently proposed serotonergic-raphe model of tonic immobility.", "contents": "Pargyline and tryptophan enhancement of tonic immobility: paradoxical attenuation with combined administration. Four experiments were conducted to examine the individual and combined effects of pargyline and tryptophan on the duration of tonic immobility in chickens. Injection of either compound alone produced a dose-dependent potentiation of tonic immobility. However, combined administration of pargyline and tryptophan resulted in a dramatic attenuation of the response and this effect was completely blocked by pretreatment with p-chlorophenylalanine. In addition to reducing the duration of tonic immobility, combined administration of pargyline and tryptophan produced a complex behavioral syndrome which may be analogous to that observed in mammals after similar drug treatment. These results suggest the need for a modification of the recently proposed serotonergic-raphe model of tonic immobility."} {"id": "PMID:158769", "title": "Determination of the optimum doses of nutrients in a diet.", "content": "For 14 days, SPF male Wistar rats with an initial weight of 60 g were given isocaloric diets (1.7 MJ/100 g diet) containing 10% protein (casein) and 5, 10, 25 and 40% fat (margarine). Two utilization parameters of the protein biological value--net protein utilization (NPU) and liver protein utilization (LPU)--were determined from protein intake and body and liver nitrogen. These results were supplemented by a study of the course of the antithetical processes of gluconeogenesis and glycolysis, of the citric acid cycle and transamination processes and of the liver and muscle amino acid spectrum. A high (40%) fat diet significantly reduced the protein biological value parameters NPU and LPU and liver and muscle amino acid values, stimulated gluconeogenesis and inhibited glycolysis and the citric acid cycle, together with associated transamination processes in the liver. Activation of these processes in the muscles provided substrates for increased gluconeogenesis. The negative effect of a low fat + high carbohydrate diet was less marked. The optimum diet for weaned rats is thus a diet containing 10% protein and 10--25% fat. The study, which submits several possible ways of determining optimum nutrient intakes under different physiological conditions shows that diets with more detailed nutrient concentrations should be used.", "contents": "Determination of the optimum doses of nutrients in a diet. For 14 days, SPF male Wistar rats with an initial weight of 60 g were given isocaloric diets (1.7 MJ/100 g diet) containing 10% protein (casein) and 5, 10, 25 and 40% fat (margarine). Two utilization parameters of the protein biological value--net protein utilization (NPU) and liver protein utilization (LPU)--were determined from protein intake and body and liver nitrogen. These results were supplemented by a study of the course of the antithetical processes of gluconeogenesis and glycolysis, of the citric acid cycle and transamination processes and of the liver and muscle amino acid spectrum. A high (40%) fat diet significantly reduced the protein biological value parameters NPU and LPU and liver and muscle amino acid values, stimulated gluconeogenesis and inhibited glycolysis and the citric acid cycle, together with associated transamination processes in the liver. Activation of these processes in the muscles provided substrates for increased gluconeogenesis. The negative effect of a low fat + high carbohydrate diet was less marked. The optimum diet for weaned rats is thus a diet containing 10% protein and 10--25% fat. The study, which submits several possible ways of determining optimum nutrient intakes under different physiological conditions shows that diets with more detailed nutrient concentrations should be used."} {"id": "PMID:158770", "title": "Role of the vagus in control of the major conduit coronary artery in the dog.", "content": "Using El Badawi and Schenk's modification of Karnovski's method for the demonstration of acetylcholinesterase, the authors found cholinergic fibres both in the perivascular connective tissue and directly in the wall (in the adventitia) of the major coronary arteries; the fibres were distributed regularly around the circumference of the arteries. In the case of the smaller intramyocardial arteries, the cholinergic fibres were concentrated at two poles of the blood vessel; none were present in the wall of the veins. The shape and topography of the coronary cholinergic arterial plexus resemble the shape and topography of the coronary sympathetic adrenergic system. In apparent contradiction of this finding, stimulation of the cervical vagus did not affect the diameter of the large coronary arteries. Since acetylcholine (6--10 micrograms/kg i.v.) produced a mean 7.4% increase in the diameter of the ramus interventricularis ventralis, we concluded that there are no postgangliar cholinergic fibres of vasomotor significance for the large coronary arteries in the cervical vagus. The specific acetylcholinesterase activity found in the wall of these vessels belongs either to cholinergic terminals whose ganglion cells are not located in the vagal ganglion, or to cholinergic axones terminating outside the wall of the large coronary arteries.", "contents": "Role of the vagus in control of the major conduit coronary artery in the dog. Using El Badawi and Schenk's modification of Karnovski's method for the demonstration of acetylcholinesterase, the authors found cholinergic fibres both in the perivascular connective tissue and directly in the wall (in the adventitia) of the major coronary arteries; the fibres were distributed regularly around the circumference of the arteries. In the case of the smaller intramyocardial arteries, the cholinergic fibres were concentrated at two poles of the blood vessel; none were present in the wall of the veins. The shape and topography of the coronary cholinergic arterial plexus resemble the shape and topography of the coronary sympathetic adrenergic system. In apparent contradiction of this finding, stimulation of the cervical vagus did not affect the diameter of the large coronary arteries. Since acetylcholine (6--10 micrograms/kg i.v.) produced a mean 7.4% increase in the diameter of the ramus interventricularis ventralis, we concluded that there are no postgangliar cholinergic fibres of vasomotor significance for the large coronary arteries in the cervical vagus. The specific acetylcholinesterase activity found in the wall of these vessels belongs either to cholinergic terminals whose ganglion cells are not located in the vagal ganglion, or to cholinergic axones terminating outside the wall of the large coronary arteries."} {"id": "PMID:158771", "title": "The age factor in blood flow in the calf and in vascular resistance at rest and in reactive hyperaemia.", "content": "The blood flow and vascular resistance in the calf were studied in two groups of healthy subjects (mean ages 22 and 49 years) at rest and in reactive hyperaemia produced by five minutes' ischaemia of the lower limb. The blood flow was determined by venous occlusive plethysmography and vascular resistance was computed from the mean blood pressure measured by auscultation on the arm and from the blood flow in the calf, at rest and during reactive hyperaemia. The resting flow and blood flows throughout practically the whole time of hyperaemia were found to be significantly smaller in young individuals. The maximal flow was significantly lower, the maximal flow time was significantly prolonged in young subjects. The recovery time and repayment of the flow debt in the two groups were the same. Vascular resistance in the calf was significantly greater in young subjects, both at rest and during dilatation. We assume from the results that the capacity of the arterial system in the lower limbs is significantly smaller in young individuals.", "contents": "The age factor in blood flow in the calf and in vascular resistance at rest and in reactive hyperaemia. The blood flow and vascular resistance in the calf were studied in two groups of healthy subjects (mean ages 22 and 49 years) at rest and in reactive hyperaemia produced by five minutes' ischaemia of the lower limb. The blood flow was determined by venous occlusive plethysmography and vascular resistance was computed from the mean blood pressure measured by auscultation on the arm and from the blood flow in the calf, at rest and during reactive hyperaemia. The resting flow and blood flows throughout practically the whole time of hyperaemia were found to be significantly smaller in young individuals. The maximal flow was significantly lower, the maximal flow time was significantly prolonged in young subjects. The recovery time and repayment of the flow debt in the two groups were the same. Vascular resistance in the calf was significantly greater in young subjects, both at rest and during dilatation. We assume from the results that the capacity of the arterial system in the lower limbs is significantly smaller in young individuals."} {"id": "PMID:158772", "title": "Lipolytic effect of TSH, glucagon and hydrocortisone on the adipose tissue of newborns and adults in vitro.", "content": "In an in vitro study, TSH stimulated glycerol release from the subcutaneous adipose tissue of newborns, but had no effect on its release from the adipose tissue of adults. Hydrocortisone stimulated only NEFA release in newborns. Glucagone had no effect on either neonatal or adult adipose tissue.", "contents": "Lipolytic effect of TSH, glucagon and hydrocortisone on the adipose tissue of newborns and adults in vitro. In an in vitro study, TSH stimulated glycerol release from the subcutaneous adipose tissue of newborns, but had no effect on its release from the adipose tissue of adults. Hydrocortisone stimulated only NEFA release in newborns. Glucagone had no effect on either neonatal or adult adipose tissue."} {"id": "PMID:158773", "title": "Isolation and properties of LC3 cells, a new cold-resistant L cell subline.", "content": "LC3 cells, selected from the L-As cells by repeated exposures to 4 degrees C for 3--6 weeks with intermittent reincubations at 36 degrees C, differ from the initial population by better survival at 4 degrees C, more rapid recovery at 36 degrees C, a higher multiplication at subnormal temperature, a higher sensitivity to supranormal temperature, increased cell size at 36 degrees and 4 degrees C, and higher oxygen consumption at 36 degrees C. These properties are the same as those described in our previously isolated cold-resistant L cell variants and are typical for the resistance to low temperature. The increased activity of alkaline phosphatase, detected in two of our cold-resistant L cell sublines, was not found in the LC3 cells and has thus no relation to decreased cold sensitivity.", "contents": "Isolation and properties of LC3 cells, a new cold-resistant L cell subline. LC3 cells, selected from the L-As cells by repeated exposures to 4 degrees C for 3--6 weeks with intermittent reincubations at 36 degrees C, differ from the initial population by better survival at 4 degrees C, more rapid recovery at 36 degrees C, a higher multiplication at subnormal temperature, a higher sensitivity to supranormal temperature, increased cell size at 36 degrees and 4 degrees C, and higher oxygen consumption at 36 degrees C. These properties are the same as those described in our previously isolated cold-resistant L cell variants and are typical for the resistance to low temperature. The increased activity of alkaline phosphatase, detected in two of our cold-resistant L cell sublines, was not found in the LC3 cells and has thus no relation to decreased cold sensitivity."} {"id": "PMID:158776", "title": "Changes in laryngeal motoneurone activity and in laryngeal calibre during the expiration reflex.", "content": "In anaesthetized and paralysed cats, the response of the laryngeal motoneurones during the expiration reflex is characterized by pronounced activation of the expiratory laryngeal motoneurones in the compressive phase and the subsequent constriction phase. In the expulsive phase the frequency of these discharges is significantly reduced. The inspiratory laryngeal motoneurones are inhibited during the reflex. The expiration reflex, in anaesthetized cats, is accompanied in the compressive phase and the subsequent constriction phase by a two-phase increase in laryngeal resistance. In the expulsive phase there is a significant drop in resistance.", "contents": "Changes in laryngeal motoneurone activity and in laryngeal calibre during the expiration reflex. In anaesthetized and paralysed cats, the response of the laryngeal motoneurones during the expiration reflex is characterized by pronounced activation of the expiratory laryngeal motoneurones in the compressive phase and the subsequent constriction phase. In the expulsive phase the frequency of these discharges is significantly reduced. The inspiratory laryngeal motoneurones are inhibited during the reflex. The expiration reflex, in anaesthetized cats, is accompanied in the compressive phase and the subsequent constriction phase by a two-phase increase in laryngeal resistance. In the expulsive phase there is a significant drop in resistance."} {"id": "PMID:158777", "title": "Cough reflex changes in local tracheitis.", "content": "The authors describe changes in the cough reflex in unanaesthetized cats with experimental local tracheitis. Inflammation was produced by a silk suture fixed in the trachea and cough was elicited by mechanical stimulation of different parts of the respiratory tract mucosa. The resultant cough values (the number of efforts, the intensity of the maximum effort and the intensity of the attack) were compared with the corresponding values in healthy cats. In animals with a tracheal suture, inflammation was confined to the trachea. The intensity of cough elicited by stimulation of this region increased significantly compared with normal (on the 15th to 17th day of inflammation), whereas cough elicited from the laryngopharyngeal and tracheobronchial region did not. On about the 20th day of inflammation the authors found a decrease in the intensity of the maximum effort of cough elicited from the inflamed part of the trachea and a decrease in the intensity of the maximum effort and the intensity of the coughing attack elicited from the laryngopharyngeal and tracheobronchial region. They assume that the decrease could have been due to the development of protective inhibition in central structures participating in integration of the cough reflex.", "contents": "Cough reflex changes in local tracheitis. The authors describe changes in the cough reflex in unanaesthetized cats with experimental local tracheitis. Inflammation was produced by a silk suture fixed in the trachea and cough was elicited by mechanical stimulation of different parts of the respiratory tract mucosa. The resultant cough values (the number of efforts, the intensity of the maximum effort and the intensity of the attack) were compared with the corresponding values in healthy cats. In animals with a tracheal suture, inflammation was confined to the trachea. The intensity of cough elicited by stimulation of this region increased significantly compared with normal (on the 15th to 17th day of inflammation), whereas cough elicited from the laryngopharyngeal and tracheobronchial region did not. On about the 20th day of inflammation the authors found a decrease in the intensity of the maximum effort of cough elicited from the inflamed part of the trachea and a decrease in the intensity of the maximum effort and the intensity of the coughing attack elicited from the laryngopharyngeal and tracheobronchial region. They assume that the decrease could have been due to the development of protective inhibition in central structures participating in integration of the cough reflex."} {"id": "PMID:158812", "title": "[The mechanical properties of callus in fractures treated by nailing or plating: an experimental study (author's transl)].", "content": "Twelve sheep were used in an experimental study on bone healing. The first metatarsal was fractured and fixed either by plating without compression or by intramedullary nailing. Three months later, the animals were sacrificed, the fractured bone removed and the mechanical properties of the callus were assessed by resistance to rupture, tangential strain measurement, the energy required for rupture, module of elasticity and the moment of inertia. It was concluded that callus was superior quantitatively as well as qualitatively after nailing. The mechanical properties of the callus wwere related to its degree of mineralisation.", "contents": "[The mechanical properties of callus in fractures treated by nailing or plating: an experimental study (author's transl)]. Twelve sheep were used in an experimental study on bone healing. The first metatarsal was fractured and fixed either by plating without compression or by intramedullary nailing. Three months later, the animals were sacrificed, the fractured bone removed and the mechanical properties of the callus were assessed by resistance to rupture, tangential strain measurement, the energy required for rupture, module of elasticity and the moment of inertia. It was concluded that callus was superior quantitatively as well as qualitatively after nailing. The mechanical properties of the callus wwere related to its degree of mineralisation."} {"id": "PMID:158814", "title": "[Blount's disease: a review of 8 cases (author's transl)].", "content": "The authors have reviewed eight cases of infantile tibia vara. All were treated operatively. Five patients were young children (less than 5 years old); they were treated by a single osteotomy into valgus and lateral rotation. Three children were older at the time of surgery. The deformity recurred in all of them and a second operation was required of elevation of the lateral tibial plateau and lateral epiplysiodesis. The authors emphasise the need for early correction of deformity to produce better mechanical function of the knee and balanced epiphyseal growth.", "contents": "[Blount's disease: a review of 8 cases (author's transl)]. The authors have reviewed eight cases of infantile tibia vara. All were treated operatively. Five patients were young children (less than 5 years old); they were treated by a single osteotomy into valgus and lateral rotation. Three children were older at the time of surgery. The deformity recurred in all of them and a second operation was required of elevation of the lateral tibial plateau and lateral epiplysiodesis. The authors emphasise the need for early correction of deformity to produce better mechanical function of the knee and balanced epiphyseal growth."} {"id": "PMID:158816", "title": "[Myotonic seizures; the action of curare or related compounds on myotonia (author's transl)].", "content": "Myotonic seizures with apnea are alarming but temporary incidents occurring during curaization of a myotonic patient. Experience with regional curaization in myotonia shows that it is induced only by suxamethonium and it is only an exaggeration of the fasciculations produced by this compound. In contrast, however, competitive curare compounds have no effect on myotonia. The myotonic seizure, which is specific to myotonia, is radically different from the other respiratory accidents common to muscular dystrophies.", "contents": "[Myotonic seizures; the action of curare or related compounds on myotonia (author's transl)]. Myotonic seizures with apnea are alarming but temporary incidents occurring during curaization of a myotonic patient. Experience with regional curaization in myotonia shows that it is induced only by suxamethonium and it is only an exaggeration of the fasciculations produced by this compound. In contrast, however, competitive curare compounds have no effect on myotonia. The myotonic seizure, which is specific to myotonia, is radically different from the other respiratory accidents common to muscular dystrophies."} {"id": "PMID:158813", "title": "[Hemivertebra. -- classification, natural history and prognosis (author's transl)].", "content": "The authors have studied a series of seventy patients with hemivertebra. Classification should be based on two criteria--firstly, that the hemivertebra can be fused or separate and secondly, vertebrae above and below the hemivertebra may or may not show transitional abnormality. The natural history may take one of three courses: 1--Deformity may be severe from the beginning in cases of separate hemivertebra associated with transitional abnormalites. 2--The deformity may be stable until the age of nine or ten years, after which a severe scoliosis or kypho-scoliosis may develop. 3--The deformity may be stable throughout the whole of the growing period. The prognosis should be based on the existence of transitional abnormalities, the characteristics of the hemisvertebra (separate or fused), the sex of the patient, assoicated congenital defects, the rotation of the hemivertebra, and the level of the deformity. Treatment should be surgical in cases with early progression during the first few years of life by excision of the hemisvertebra associated with correction using Harrington rods. At the thoracic level, this surgical procedure is dangerous and spine fusion is more appropriate. The second period for surgical treatment is at puberty, either by spine fusion or correction and fusion. At this age, excision of the hemivertebra may still be indicated in the lumbar spine.", "contents": "[Hemivertebra. -- classification, natural history and prognosis (author's transl)]. The authors have studied a series of seventy patients with hemivertebra. Classification should be based on two criteria--firstly, that the hemivertebra can be fused or separate and secondly, vertebrae above and below the hemivertebra may or may not show transitional abnormality. The natural history may take one of three courses: 1--Deformity may be severe from the beginning in cases of separate hemivertebra associated with transitional abnormalites. 2--The deformity may be stable until the age of nine or ten years, after which a severe scoliosis or kypho-scoliosis may develop. 3--The deformity may be stable throughout the whole of the growing period. The prognosis should be based on the existence of transitional abnormalities, the characteristics of the hemisvertebra (separate or fused), the sex of the patient, assoicated congenital defects, the rotation of the hemivertebra, and the level of the deformity. Treatment should be surgical in cases with early progression during the first few years of life by excision of the hemisvertebra associated with correction using Harrington rods. At the thoracic level, this surgical procedure is dangerous and spine fusion is more appropriate. The second period for surgical treatment is at puberty, either by spine fusion or correction and fusion. At this age, excision of the hemivertebra may still be indicated in the lumbar spine."} {"id": "PMID:158822", "title": "Sacro-iliac joint scanning with technetium-99 diphosphonate.", "content": "Quantitative sacro-iliac (SI) joint scanning with methylene diphosphonate labelled with technetium-99 (99TcMDP) was performed in 25 control patients, in 16 patients with definite ankylosing spondylitis, in 23 patients with mechanical low back pain, and in 12 patients with seronegative arthritis. The mean radio-isotope index in the control group was 1.2 +/- 0.15. The highest value was 1.5. Values in excess of 1.5 were seen in patients with clinically active ankylosing spondylitis but not those with inactive disease. Three of the 12 seronegative arthritis patients (without clinical or radiological evidence of sacro-iliitis) had elevated values: all of these were positive for HL-A B27. An important finding was that six of the 23 patients with mechanical or non-specific low back pain had values above 1.5, unassociated with B27. These data emphasize the need for caution in the interpretation of abnormal sacro-iliac scans. Radio-isotope bone scanning can provide a qualitative and quantitative assessment of inflammatory activity in joints with minimal radiation exposure. Various authors have shown its value in providing early evidence of sacro-iliitis (Russell et al., 1975; Namey et al., 1977). In this study, methylene diphosphonate labelled with technetium-99 (99TcMMDP) has been used to produce quantitative sacro-iliac scans in order to evaluate sacro-iliac disease in four groups of patients presenting with or without low back pain.", "contents": "Sacro-iliac joint scanning with technetium-99 diphosphonate. Quantitative sacro-iliac (SI) joint scanning with methylene diphosphonate labelled with technetium-99 (99TcMDP) was performed in 25 control patients, in 16 patients with definite ankylosing spondylitis, in 23 patients with mechanical low back pain, and in 12 patients with seronegative arthritis. The mean radio-isotope index in the control group was 1.2 +/- 0.15. The highest value was 1.5. Values in excess of 1.5 were seen in patients with clinically active ankylosing spondylitis but not those with inactive disease. Three of the 12 seronegative arthritis patients (without clinical or radiological evidence of sacro-iliitis) had elevated values: all of these were positive for HL-A B27. An important finding was that six of the 23 patients with mechanical or non-specific low back pain had values above 1.5, unassociated with B27. These data emphasize the need for caution in the interpretation of abnormal sacro-iliac scans. Radio-isotope bone scanning can provide a qualitative and quantitative assessment of inflammatory activity in joints with minimal radiation exposure. Various authors have shown its value in providing early evidence of sacro-iliitis (Russell et al., 1975; Namey et al., 1977). In this study, methylene diphosphonate labelled with technetium-99 (99TcMMDP) has been used to produce quantitative sacro-iliac scans in order to evaluate sacro-iliac disease in four groups of patients presenting with or without low back pain."} {"id": "PMID:158826", "title": "Telecommunication performance of persons with hearing handicap in relation to speech reception threshold.", "content": "This study is concerned with the ability of hearing-impaired persons to perceive speech via the telephone and in particular with the possible benefit gained by the use of different kinds of auxiliary equipment (receiver amplifier, extra watch receiver, hearing aid in telemagnetic or microphone position, so-called combined amplifier, and combinations of these). In 203 hard-of-hearing subjects, grouped according to the speech reception threshold (SRT) of the better ear, the efficiency of the devices under test was investigated at two different line attenuations, one representing a good telephone connection and one representing a rather poor connection. It is concluded that persons with a slight hearing impairment (SRT:0--25 dB in the better ear) are able to use the telephone without special devices. The same applies to the majority of those with moderate hearing impairment (SRT:30--45 dB). For persons having a more severe hearing loss, a telephone with a receiving amplifier, or the individual hearing aid combined with the ordinary telephone set, can largely compensate for difficulties experienced when using the telephone. To complete the experiments, the audibility of a number of telephone bells was assessed. The bell in the standard set had low audibility for all the investigated groups of persons. Some of the other sound sources offered somewhat less difficulty.", "contents": "Telecommunication performance of persons with hearing handicap in relation to speech reception threshold. This study is concerned with the ability of hearing-impaired persons to perceive speech via the telephone and in particular with the possible benefit gained by the use of different kinds of auxiliary equipment (receiver amplifier, extra watch receiver, hearing aid in telemagnetic or microphone position, so-called combined amplifier, and combinations of these). In 203 hard-of-hearing subjects, grouped according to the speech reception threshold (SRT) of the better ear, the efficiency of the devices under test was investigated at two different line attenuations, one representing a good telephone connection and one representing a rather poor connection. It is concluded that persons with a slight hearing impairment (SRT:0--25 dB in the better ear) are able to use the telephone without special devices. The same applies to the majority of those with moderate hearing impairment (SRT:30--45 dB). For persons having a more severe hearing loss, a telephone with a receiving amplifier, or the individual hearing aid combined with the ordinary telephone set, can largely compensate for difficulties experienced when using the telephone. To complete the experiments, the audibility of a number of telephone bells was assessed. The bell in the standard set had low audibility for all the investigated groups of persons. Some of the other sound sources offered somewhat less difficulty."} {"id": "PMID:158827", "title": "Effect of pentoxifylline on red cell flexibility and cation transport in healthy subjects and patients with hereditary spherocytosis.", "content": "The effect of pentoxifylline (3,7-dimethyl-1-(5-oxo-hexyl)-xanthine) on the flexibility of red cells was studied using a filtration method in which the red cells are forced, at a constant flow-rate, through a porous polycarbonate membrane. The filtration pressure reflects red cell rigidity and the amount of Hb released from the disrupted cells ('free Hb') red cell fragility. The advantage of this method is that it allows the two important determinants of red cell flexibility, rigidity and fragility, to be studied simultaneously. Pentoxifylline significantly improved normal red cell flexibility both in vivo and in vitro as judged by this method. The impaired flexibility of red cells from patients with congenital or hereditary spherocytosis (HS) was aggravated by pentoxifylline in vitro. A similar effect of pentoxifylline was also observed on red cells from relatives of HS patients. The effect of pentoxifylline on Ca2+ transport and Ca2+-Mg2+-ATPase activity in red cells from normal and HS patients was investigated. Under in vitro conditions pentoxifylline did not affect the Ca2+-Mg2+-ATPase activity of or Ca2+ efflux from normal and HS red cells. Neither the influx of monovalent cations (Na+, Rb+) or the osmotic resistance of normal or HS red cells was affected by pentoxifylline.", "contents": "Effect of pentoxifylline on red cell flexibility and cation transport in healthy subjects and patients with hereditary spherocytosis. The effect of pentoxifylline (3,7-dimethyl-1-(5-oxo-hexyl)-xanthine) on the flexibility of red cells was studied using a filtration method in which the red cells are forced, at a constant flow-rate, through a porous polycarbonate membrane. The filtration pressure reflects red cell rigidity and the amount of Hb released from the disrupted cells ('free Hb') red cell fragility. The advantage of this method is that it allows the two important determinants of red cell flexibility, rigidity and fragility, to be studied simultaneously. Pentoxifylline significantly improved normal red cell flexibility both in vivo and in vitro as judged by this method. The impaired flexibility of red cells from patients with congenital or hereditary spherocytosis (HS) was aggravated by pentoxifylline in vitro. A similar effect of pentoxifylline was also observed on red cells from relatives of HS patients. The effect of pentoxifylline on Ca2+ transport and Ca2+-Mg2+-ATPase activity in red cells from normal and HS patients was investigated. Under in vitro conditions pentoxifylline did not affect the Ca2+-Mg2+-ATPase activity of or Ca2+ efflux from normal and HS red cells. Neither the influx of monovalent cations (Na+, Rb+) or the osmotic resistance of normal or HS red cells was affected by pentoxifylline."} {"id": "PMID:158828", "title": "Suppressor cells induced by purified protein derivative of tuberculin (PPD): the suppression is mediated by cells that proliferate in response to stimulation with PPD.", "content": "Lymphocytes stimulated with purified protein derivative of tuberculin (PPD) were found to inhibit the PPD stimulation of fresh, autologous lymphocytes. This suppressor effect was exerted after preincubation with both high and low concentrations of PPD. Optimal suppression occurred after preincubation with PPD in concentrations of 5 micrograms/ml and higher, the same concentrations that gave optimal stimulation of DNA synthetsis in primary cultures. The suppressor effect was abolished completely by 'hot pulse' treatment and partly by treatment with colchicine during PPD preincubation, showing that the PPD-induced suppressr cells are generated by cell division. When fresh lymphocytes were incubated together with PPD-pretreated cells in cultures that were not stimulated with PPD, the PPD-stimulated lymphocytes exerted a stimulatory effect on the fresh lymphocytes. This effect was maximal for cells preincubated for 1 h with PPD, decreasing with increasing duration of preincubation with PPD. Possible explanations of this observation are discussed.", "contents": "Suppressor cells induced by purified protein derivative of tuberculin (PPD): the suppression is mediated by cells that proliferate in response to stimulation with PPD. Lymphocytes stimulated with purified protein derivative of tuberculin (PPD) were found to inhibit the PPD stimulation of fresh, autologous lymphocytes. This suppressor effect was exerted after preincubation with both high and low concentrations of PPD. Optimal suppression occurred after preincubation with PPD in concentrations of 5 micrograms/ml and higher, the same concentrations that gave optimal stimulation of DNA synthetsis in primary cultures. The suppressor effect was abolished completely by 'hot pulse' treatment and partly by treatment with colchicine during PPD preincubation, showing that the PPD-induced suppressr cells are generated by cell division. When fresh lymphocytes were incubated together with PPD-pretreated cells in cultures that were not stimulated with PPD, the PPD-stimulated lymphocytes exerted a stimulatory effect on the fresh lymphocytes. This effect was maximal for cells preincubated for 1 h with PPD, decreasing with increasing duration of preincubation with PPD. Possible explanations of this observation are discussed."} {"id": "PMID:158823", "title": "Functions of T cells and recruitment of cellular response after in vitro mitogenic stimulation of lymphocytes in chronic lymphocytic leukaemia.", "content": "In vitro stimulation of peripheral blood lymphocytes from ten patients with chronic lymphocytic leukaemia (CLL) was investigated under various culture conditions. It was confirmed that the mitogenic reactivity of whole cell populations (PBL) was delayed and depressed. When CLL rosette-forming cells (RFC) were stimulated, their 3H-thymidine uptake was increased, but the pattern of the response was similar to that of whole PBL, thus suggesting some impairment of these cells. Furthermore, in order to evaluate the possible recruitment of B cells, generally thought to be unresponsive, some co-culture experiments were performed in which 10(4) normal lymphocytes and 10(5) CLL whole PBL or RFC-depleted cell populations were stimulated with mitogens. An amplified response of the CLL lymphocytes was obtained in all co-cultures, and this effect was more evident when specific T cell stimulants were used; autologous CLL T lymphocytes, on the contrary, failed to display such a 'synergic' effect. These results indicate that normal lymphocytes are able to recruit a large number of CLL lymphocytes in the mitogenic response; furthermore, the fact that in co-cultures of CLL T-depleted fractions a better response was obtained with T cell mitogens suggests that the definition of CLL as a clonal expansion of unresponsive 'B' lymphocytes may be inadequate.", "contents": "Functions of T cells and recruitment of cellular response after in vitro mitogenic stimulation of lymphocytes in chronic lymphocytic leukaemia. In vitro stimulation of peripheral blood lymphocytes from ten patients with chronic lymphocytic leukaemia (CLL) was investigated under various culture conditions. It was confirmed that the mitogenic reactivity of whole cell populations (PBL) was delayed and depressed. When CLL rosette-forming cells (RFC) were stimulated, their 3H-thymidine uptake was increased, but the pattern of the response was similar to that of whole PBL, thus suggesting some impairment of these cells. Furthermore, in order to evaluate the possible recruitment of B cells, generally thought to be unresponsive, some co-culture experiments were performed in which 10(4) normal lymphocytes and 10(5) CLL whole PBL or RFC-depleted cell populations were stimulated with mitogens. An amplified response of the CLL lymphocytes was obtained in all co-cultures, and this effect was more evident when specific T cell stimulants were used; autologous CLL T lymphocytes, on the contrary, failed to display such a 'synergic' effect. These results indicate that normal lymphocytes are able to recruit a large number of CLL lymphocytes in the mitogenic response; furthermore, the fact that in co-cultures of CLL T-depleted fractions a better response was obtained with T cell mitogens suggests that the definition of CLL as a clonal expansion of unresponsive 'B' lymphocytes may be inadequate."} {"id": "PMID:158829", "title": "[Hemoglobin D Punjab. Apropos of 2 families].", "content": "Two families who are carriers of hemoglobin DPunjab in the heterozygous state are described. This is the first time hemoglobin DPunjab has been reported in Switzerland. The propositus of the first family had two periods of acute hemolysis, probably drug-induced, which were followed by reversible renal complications and which led to the discovery of the hemoglobin. Study of the second family was undertaken because of anemia in one of its members.", "contents": "[Hemoglobin D Punjab. Apropos of 2 families]. Two families who are carriers of hemoglobin DPunjab in the heterozygous state are described. This is the first time hemoglobin DPunjab has been reported in Switzerland. The propositus of the first family had two periods of acute hemolysis, probably drug-induced, which were followed by reversible renal complications and which led to the discovery of the hemoglobin. Study of the second family was undertaken because of anemia in one of its members."} {"id": "PMID:158830", "title": "Post-operative analgesia following laparoscopic sterilization.", "content": "In a retrospective survey of 161 consecutive cases of laparoscopic sterilization performed over a period of six months, 41.6 per cent were by tubal diathermy and 58.4 per cent by silastic Falope ring application. It was found that, in the latter group 28.7 per cent of patients required major post-operative analgesia, while in the group treated by diathermy only 4.5 per cent required such sedation.", "contents": "Post-operative analgesia following laparoscopic sterilization. In a retrospective survey of 161 consecutive cases of laparoscopic sterilization performed over a period of six months, 41.6 per cent were by tubal diathermy and 58.4 per cent by silastic Falope ring application. It was found that, in the latter group 28.7 per cent of patients required major post-operative analgesia, while in the group treated by diathermy only 4.5 per cent required such sedation."} {"id": "PMID:158831", "title": "Complications of 'dermolipectomy' as an encore to abdominal operative procedures.", "content": "Four examples are used to illustrate the disastrous results of 'dermolipectomies' done as an encore to abdominal operative procedures. These results fall far short of the ideal lipectomy, which can at times be aesthetically pleasing when one considers the extent of the original deformity.", "contents": "Complications of 'dermolipectomy' as an encore to abdominal operative procedures. Four examples are used to illustrate the disastrous results of 'dermolipectomies' done as an encore to abdominal operative procedures. These results fall far short of the ideal lipectomy, which can at times be aesthetically pleasing when one considers the extent of the original deformity."} {"id": "PMID:158837", "title": "Blind and disabled persons awarded federally administered SSI payments, 1975.", "content": "State agencies made medical determinations on 975,000 applications filed by the blind and disabled in 1975. Forty percent were found eligible for federally administered payments, and 60 percent were found ineligible. Nine out of 10 of the awardees were adults. Forty percent of these adults either had no occupation or no occupation was reported. Among both adults and children, the leading cause of disability was mental illness. Nearly 1 out of 3 adults was awarded benefits on the basis of mental disorders. The proportion of children determined disabled by mental illness was about twice that of adults. More than one-half of all children awarded benefits were mentally retarded. Among adults, the second most frequent disabling impairment was cardio-vascular disease; among children, it was diseases of the nervous system and sense organs.", "contents": "Blind and disabled persons awarded federally administered SSI payments, 1975. State agencies made medical determinations on 975,000 applications filed by the blind and disabled in 1975. Forty percent were found eligible for federally administered payments, and 60 percent were found ineligible. Nine out of 10 of the awardees were adults. Forty percent of these adults either had no occupation or no occupation was reported. Among both adults and children, the leading cause of disability was mental illness. Nearly 1 out of 3 adults was awarded benefits on the basis of mental disorders. The proportion of children determined disabled by mental illness was about twice that of adults. More than one-half of all children awarded benefits were mentally retarded. Among adults, the second most frequent disabling impairment was cardio-vascular disease; among children, it was diseases of the nervous system and sense organs."} {"id": "PMID:158849", "title": "Operational diagnostics of lungworm infections in cattle. Preliminary investigation into the usefulness of the indirect haemagglutination.", "content": "To give an impression of the usefulness of indirect haemagglutination (IHA) in the diagnosis of lungworm infections in cattle under practical conditions, five calves vaccinated against Dictyocaulus viviparus and five unvaccinated calves were periodically subjected to clinical, parasitological, and serological examinations over a period of seven months. All calves grazed on a lungworm-infected plot. 82% of the observations in unvaccinated calves, which were positive with respect to one or more of the used parameters, concerned IHA-positive animals which, however, showed negative results with the parasitic parameters. The titre variation of the serological examination was a further indication of the fact that the IHA detected antibodies against lungworm antigens. No indications of false positive reactions were obtained. An investigation carried out on 46 farms on the correlation between serological and clinical findings on lungworm infections revealed a positive correlation in 80% of the groups between results obtained with both methods. The authors consider that IHA offers good prospects for the diagnosis of lungworm infections.", "contents": "Operational diagnostics of lungworm infections in cattle. Preliminary investigation into the usefulness of the indirect haemagglutination. To give an impression of the usefulness of indirect haemagglutination (IHA) in the diagnosis of lungworm infections in cattle under practical conditions, five calves vaccinated against Dictyocaulus viviparus and five unvaccinated calves were periodically subjected to clinical, parasitological, and serological examinations over a period of seven months. All calves grazed on a lungworm-infected plot. 82% of the observations in unvaccinated calves, which were positive with respect to one or more of the used parameters, concerned IHA-positive animals which, however, showed negative results with the parasitic parameters. The titre variation of the serological examination was a further indication of the fact that the IHA detected antibodies against lungworm antigens. No indications of false positive reactions were obtained. An investigation carried out on 46 farms on the correlation between serological and clinical findings on lungworm infections revealed a positive correlation in 80% of the groups between results obtained with both methods. The authors consider that IHA offers good prospects for the diagnosis of lungworm infections."} {"id": "PMID:158850", "title": "Veterinary experiences as a Japanese prisoner of war and ex-POW along the Burma railroad from 1942 to January 1946.", "content": "As a prisoner of war the writer was working for nearly three years in different POW camps, and outside them, along the Burma railway from Thanbyuyzat in southern Burma up to Kanchanabury in Thiland. In the army of the Netherlands-Indian archipelago (KNIL) he had the military rank of reserve horse-doctor. In civilian life he was attached to the Veterinary Institute in Buitenzorg(now Bogor) as a veterinary bacteriologist. His task as a POW became that of meathygienist and supervisor of the living animals in the camps. In this function he diagnosed swine fever in growing pigs which had mainly been fed on the offal of the Japanese kitchen. The acute course and the pathological alterations observed during the post-mortem examinations were identical with those of the Southern-African type of the disease. In slaughter cattle the author diagnosed some cases of lung tuberculosis, one of anthrax, several of rinderpest, some of rhinal granulomatosis and one of foot and mouth disease. In chickens he found NCD (pseudo-fowlpest) and in ducklings a mortal disease which the author then called 'keeling disease' but which he many years later, recognized as virus hepatitis. As assistant bacteriologist and ex-POW he joined the British regimental hospital in Bangkok. Here he had the apportunity to assist the bacteriologist pathologist, Maj. C. R. Peck IMS/IAMC in diagnosing the first case of melioidosis in an ex-POW of the KNIL who died from the sub-acute infection, notwithstanding treatment in the hospital with sulfa-drugs and penicillin.", "contents": "Veterinary experiences as a Japanese prisoner of war and ex-POW along the Burma railroad from 1942 to January 1946. As a prisoner of war the writer was working for nearly three years in different POW camps, and outside them, along the Burma railway from Thanbyuyzat in southern Burma up to Kanchanabury in Thiland. In the army of the Netherlands-Indian archipelago (KNIL) he had the military rank of reserve horse-doctor. In civilian life he was attached to the Veterinary Institute in Buitenzorg(now Bogor) as a veterinary bacteriologist. His task as a POW became that of meathygienist and supervisor of the living animals in the camps. In this function he diagnosed swine fever in growing pigs which had mainly been fed on the offal of the Japanese kitchen. The acute course and the pathological alterations observed during the post-mortem examinations were identical with those of the Southern-African type of the disease. In slaughter cattle the author diagnosed some cases of lung tuberculosis, one of anthrax, several of rinderpest, some of rhinal granulomatosis and one of foot and mouth disease. In chickens he found NCD (pseudo-fowlpest) and in ducklings a mortal disease which the author then called 'keeling disease' but which he many years later, recognized as virus hepatitis. As assistant bacteriologist and ex-POW he joined the British regimental hospital in Bangkok. Here he had the apportunity to assist the bacteriologist pathologist, Maj. C. R. Peck IMS/IAMC in diagnosing the first case of melioidosis in an ex-POW of the KNIL who died from the sub-acute infection, notwithstanding treatment in the hospital with sulfa-drugs and penicillin."} {"id": "PMID:158851", "title": "Aortic stenosis complicated by severe calcification of the wall of the ascending and transverse aorta: management by use of left ventricular to aortic composite conduit. Report of two cases.", "content": "The use of left ventricular aortic composite conduits in 2 patients with severe intramural calcification of both the ascending and the transverse aorta is reported. This method is felt to be superior to conventional aortic valve replacement, when the texture of the aortic wall does not allow cross clamping or secure closure.", "contents": "Aortic stenosis complicated by severe calcification of the wall of the ascending and transverse aorta: management by use of left ventricular to aortic composite conduit. Report of two cases. The use of left ventricular aortic composite conduits in 2 patients with severe intramural calcification of both the ascending and the transverse aorta is reported. This method is felt to be superior to conventional aortic valve replacement, when the texture of the aortic wall does not allow cross clamping or secure closure."} {"id": "PMID:158852", "title": "Backstimulation by blastogenic factor in the primed LD typing test: possible role in anomalous responses.", "content": "The anomalous false-positive results often found in the primed lymphocyte typing (PLT) test seem to be partially due to the release of blastogenic factor (BF) from the stimulating cell, resulting in back stimulation of the primed lymphocyte. These anomalous responses can be greatly reduced by treating the stimulator cell with high doses of irradiation or with puromycin.", "contents": "Backstimulation by blastogenic factor in the primed LD typing test: possible role in anomalous responses. The anomalous false-positive results often found in the primed lymphocyte typing (PLT) test seem to be partially due to the release of blastogenic factor (BF) from the stimulating cell, resulting in back stimulation of the primed lymphocyte. These anomalous responses can be greatly reduced by treating the stimulator cell with high doses of irradiation or with puromycin."} {"id": "PMID:158853", "title": "Study on HLA system in IgA nephropathy.", "content": "Forty Japanese patients with IgA nephropathy were typed for HLA-A and HLA-B using local antisera. Thirty-seven of these patients were typed for HLA-D using homozygous cells \"En\", now known to be strongly related to DRw6. Forty-six patients with chronic hemodialysis were used as patient controls for renal disease and 115 healthy individuals were used as normal controls. The frequency of HLA-DEn was significantly increased in 17 out of 37 patients with IgA nephropathy, (46%) (normal controls 18.3%) (P less than 0.0007). Although the occurrence of HLA-B12 was high, it was not significant, i.e. 11 out of 40 (27.5%). These results suggest that some abnormality in the genes of patients with IgA nephropathy is more closely associated with the HLA-D region than the HLA-A or B regions.", "contents": "Study on HLA system in IgA nephropathy. Forty Japanese patients with IgA nephropathy were typed for HLA-A and HLA-B using local antisera. Thirty-seven of these patients were typed for HLA-D using homozygous cells \"En\", now known to be strongly related to DRw6. Forty-six patients with chronic hemodialysis were used as patient controls for renal disease and 115 healthy individuals were used as normal controls. The frequency of HLA-DEn was significantly increased in 17 out of 37 patients with IgA nephropathy, (46%) (normal controls 18.3%) (P less than 0.0007). Although the occurrence of HLA-B12 was high, it was not significant, i.e. 11 out of 40 (27.5%). These results suggest that some abnormality in the genes of patients with IgA nephropathy is more closely associated with the HLA-D region than the HLA-A or B regions."} {"id": "PMID:158854", "title": "The effect of blood transfusion on the immune response and renal graft survival in the Chacma baboon.", "content": "There is uncertainty about the role of blood transfusion of potential kidney graft recipients. In this study baboons were transfused under conditions mimicking the clinical situation and then callenged with kidney allografts. Eleven baboons were transfused 10 times with blood from different donors. Lymphocytotoxic antibodies induced against the separated B and T cells of a panel of 12 normal baboons were as follows: B-T- 30%; B+T- 3%; B-T+ 1% and B+T+ 66%. Kidney transplantations were done from donors against which the recipients had negative B-T- cross-matches. Median allograft survival time (MST) of 12 days in this group, which was immunosuppressed with azathioprine and prednisolone, was not prolonged when compared with non-transfused, immunosuppressed animals (MST 12 days). A second group of 14 animals was screened for cytotoxins after each transfusion against a panel of five to six normal baboons. The antibody profile of 80 combinations tested after three transfusions was as follows: B-T- 65%; B+T- 16%, B-T+ 0% and B+T+ 19%. Transplantation was with donors against which the transfused recipient had formed B+T- antibodies. Kidney allograft survival was again not prolonged (MST 13 days) but the mean serum creatinine level 8 days after transplantation was significantly lower than that observed in the first group.", "contents": "The effect of blood transfusion on the immune response and renal graft survival in the Chacma baboon. There is uncertainty about the role of blood transfusion of potential kidney graft recipients. In this study baboons were transfused under conditions mimicking the clinical situation and then callenged with kidney allografts. Eleven baboons were transfused 10 times with blood from different donors. Lymphocytotoxic antibodies induced against the separated B and T cells of a panel of 12 normal baboons were as follows: B-T- 30%; B+T- 3%; B-T+ 1% and B+T+ 66%. Kidney transplantations were done from donors against which the recipients had negative B-T- cross-matches. Median allograft survival time (MST) of 12 days in this group, which was immunosuppressed with azathioprine and prednisolone, was not prolonged when compared with non-transfused, immunosuppressed animals (MST 12 days). A second group of 14 animals was screened for cytotoxins after each transfusion against a panel of five to six normal baboons. The antibody profile of 80 combinations tested after three transfusions was as follows: B-T- 65%; B+T- 16%, B-T+ 0% and B+T+ 19%. Transplantation was with donors against which the transfused recipient had formed B+T- antibodies. Kidney allograft survival was again not prolonged (MST 13 days) but the mean serum creatinine level 8 days after transplantation was significantly lower than that observed in the first group."} {"id": "PMID:158855", "title": "Physiologically induced changes in intramembranous particle frequency in the axons of an osmoconforming bivalve.", "content": "Freeze-fractured axonal membrane surfaces from the connectives of Mytilus edulis show an increment in particle frequency of 52% (fixed tissues) or 68% (unfixed tissues) after long-term adaptation to low salinity. Particle size distribution was unaffected by osmotic adaptation, but was significantly different in fixed and unfixed material. The possibility that these structural changes reflect the known increase in sodium pump frequency in this osmoconforming tissue is considered.", "contents": "Physiologically induced changes in intramembranous particle frequency in the axons of an osmoconforming bivalve. Freeze-fractured axonal membrane surfaces from the connectives of Mytilus edulis show an increment in particle frequency of 52% (fixed tissues) or 68% (unfixed tissues) after long-term adaptation to low salinity. Particle size distribution was unaffected by osmotic adaptation, but was significantly different in fixed and unfixed material. The possibility that these structural changes reflect the known increase in sodium pump frequency in this osmoconforming tissue is considered."} {"id": "PMID:158859", "title": "Steroid analysis of human apocrine secretion.", "content": "Analysis of the secretion of the human apocrine gland has shown the presence of dehydroepiandrosterone and androsterone sulfates, two androgen steroids previously identified in axillary sweat. These steroid sulfates were characterized by the gas chromatographic/mass spectrometric analysis of the odorous steroids formed on direct injection of the apocrine secretion into the host gas chromatographic injector. No spectral evidence was found for the presence of the delta16-androgen steroids which have axillary-like odors and have also been reported in axillary sweat. Cholesterol was the major steroid component of the secretion.", "contents": "Steroid analysis of human apocrine secretion. Analysis of the secretion of the human apocrine gland has shown the presence of dehydroepiandrosterone and androsterone sulfates, two androgen steroids previously identified in axillary sweat. These steroid sulfates were characterized by the gas chromatographic/mass spectrometric analysis of the odorous steroids formed on direct injection of the apocrine secretion into the host gas chromatographic injector. No spectral evidence was found for the presence of the delta16-androgen steroids which have axillary-like odors and have also been reported in axillary sweat. Cholesterol was the major steroid component of the secretion."} {"id": "PMID:158860", "title": "[Possibilities of retaining teeth in children from the viewpoint of ambulatory dental surgery].", "content": "In the sphere of outpatient oral surgery, the treatment of children definitely offers possibilities of retaining teeth which are described in detail. The treatment should always be an individual one, and it should consider the pecularities of the growing organism.", "contents": "[Possibilities of retaining teeth in children from the viewpoint of ambulatory dental surgery]. In the sphere of outpatient oral surgery, the treatment of children definitely offers possibilities of retaining teeth which are described in detail. The treatment should always be an individual one, and it should consider the pecularities of the growing organism."} {"id": "PMID:158862", "title": "One-way mixed lymphocyte culture: differences between Chinese and Caucasian stimulator cells.", "content": "In \"standardized\" one-way mixed lymphocyte cultures, a pool of blood lymphocytes from randomly chosen Chinese subjects was a significantly stronger stimulus to Caucasian responder lymphocytes than was a pool of allogeneic cells from Caucasians. In contrast, Chinese lymphocytes did not respond more strongly to Caucasian cells than to Chinese cells. This could not be explained by an inherent racial difference in the capacity of blood lymphocytes to undergo blastogenesis. The implications of these findings for organ transplantation and routine testing of cell-mediated immune function are discussed.", "contents": "One-way mixed lymphocyte culture: differences between Chinese and Caucasian stimulator cells. In \"standardized\" one-way mixed lymphocyte cultures, a pool of blood lymphocytes from randomly chosen Chinese subjects was a significantly stronger stimulus to Caucasian responder lymphocytes than was a pool of allogeneic cells from Caucasians. In contrast, Chinese lymphocytes did not respond more strongly to Caucasian cells than to Chinese cells. This could not be explained by an inherent racial difference in the capacity of blood lymphocytes to undergo blastogenesis. The implications of these findings for organ transplantation and routine testing of cell-mediated immune function are discussed."} {"id": "PMID:158863", "title": "Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy.", "content": "The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.", "contents": "Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy. The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species."} {"id": "PMID:158865", "title": "[Cellular energy functions of a subline of mouse fibroblasts resistent to the action of ethidium bromide].", "content": "The respiration of subline Leb-25 cells, resistant to ethidium bromide (EB, 25 g/ml), is 2.5 times slower than the respiration of parental L cells of mouse fibroblasts. The EB resistant cells have a normal level of ATP. Disturbances of mitochondrial functions can be observed such as a defect of the succinate dehydrogenase complex and the uncoupling of respiration and oxidative phosphorylation in mitochondria of Leb-25 cells.", "contents": "[Cellular energy functions of a subline of mouse fibroblasts resistent to the action of ethidium bromide]. The respiration of subline Leb-25 cells, resistant to ethidium bromide (EB, 25 g/ml), is 2.5 times slower than the respiration of parental L cells of mouse fibroblasts. The EB resistant cells have a normal level of ATP. Disturbances of mitochondrial functions can be observed such as a defect of the succinate dehydrogenase complex and the uncoupling of respiration and oxidative phosphorylation in mitochondria of Leb-25 cells."} {"id": "PMID:158869", "title": "Breast hamartomas. An important entity in mammary pathology.", "content": "1. Fifteen cases of a rather distinct entity of tumour-like lesion in the breast are presented. 2. They have a distinct mammographic appearance and can be easily shelled out at surgery, leaving symmetrical breasts. 3. They are well-circumscribed lumps of varying size with a smooth surface. 4. Microscopically they show normal or dysplastic glandular structures of lobules and ducts, without neoplastic features, within a prominent fibrous stroma. The lesions appear to be closely related to adenolipomas.", "contents": "Breast hamartomas. An important entity in mammary pathology. 1. Fifteen cases of a rather distinct entity of tumour-like lesion in the breast are presented. 2. They have a distinct mammographic appearance and can be easily shelled out at surgery, leaving symmetrical breasts. 3. They are well-circumscribed lumps of varying size with a smooth surface. 4. Microscopically they show normal or dysplastic glandular structures of lobules and ducts, without neoplastic features, within a prominent fibrous stroma. The lesions appear to be closely related to adenolipomas."} {"id": "PMID:158870", "title": "Interstitial fibrosis of the renal cortex in minimal change lesion and its correlation with renal function. A quantitative study.", "content": "Morphometric investigations were performed in 18 biopsies from 16 patients with the nephrotic syndrome and 10 biopsies from 10 patients with mild proteinuria not associated with oedema. All biopsies showed normal glomeruli on light microscopy. The interstitial fibrosis was significantly increased in both patient groups compared with controls, and it was greater in the patients with mild proteinuria than in the group with nephrotic syndrome. A significant negative correlation was present between the degree of fibrosis and renal function in both groups of patients.", "contents": "Interstitial fibrosis of the renal cortex in minimal change lesion and its correlation with renal function. A quantitative study. Morphometric investigations were performed in 18 biopsies from 16 patients with the nephrotic syndrome and 10 biopsies from 10 patients with mild proteinuria not associated with oedema. All biopsies showed normal glomeruli on light microscopy. The interstitial fibrosis was significantly increased in both patient groups compared with controls, and it was greater in the patients with mild proteinuria than in the group with nephrotic syndrome. A significant negative correlation was present between the degree of fibrosis and renal function in both groups of patients."} {"id": "PMID:158872", "title": "[Hypertensive lesions of pulmonary arteries in chronic inflammatory lung diseases (author's transl)].", "content": "150 cases of chronic inflammatory lung diseases of unknown aetiology and assumed hyperergic (immuno-reactive) pathogenesis were examined for hypertensive pulmonary arterial lesions and for chronic cor pulmonale. Hypertensive lesions of the small pulmonary arteries were found in more than half of the cases with chronic disorders of long duration, but were inconspicuous in diseases of acute progressive character. Hypertensive lesions were found regularly in chronic interstitial pneumonia, frequently in scleroderma and rheumatoid arthritis and occasionally in dermatomyositis and disseminated lupus erythematosus. Chronic Cor pulmonale occurred in 16% of the cases with hypertensive arterial lesions of grade I (hypertrophy of media) and in 50% of grade II/III (hypertrophy of media and intimal fibrosis). Interstitial lung fibrosis plays an important role in the pathogenesis of cor pulmonale: two thirds of the cases with interstitial lung fibrosis had developed cor pulmonale and all the cases with cor pulmonale also had interstitial lung fibrosis. Hypertensive arterial lesions of grade IV-VI according to Heath and Edwards (angiitis, plexogenic and angiomatoid lesions) have been described in severe cases of pulmonary hypertension (congenital cardiac shunts, primary pulmonary hypertension). In secondary forms of pulmonary hypertension, as represented by our material, these changes are of little importance.", "contents": "[Hypertensive lesions of pulmonary arteries in chronic inflammatory lung diseases (author's transl)]. 150 cases of chronic inflammatory lung diseases of unknown aetiology and assumed hyperergic (immuno-reactive) pathogenesis were examined for hypertensive pulmonary arterial lesions and for chronic cor pulmonale. Hypertensive lesions of the small pulmonary arteries were found in more than half of the cases with chronic disorders of long duration, but were inconspicuous in diseases of acute progressive character. Hypertensive lesions were found regularly in chronic interstitial pneumonia, frequently in scleroderma and rheumatoid arthritis and occasionally in dermatomyositis and disseminated lupus erythematosus. Chronic Cor pulmonale occurred in 16% of the cases with hypertensive arterial lesions of grade I (hypertrophy of media) and in 50% of grade II/III (hypertrophy of media and intimal fibrosis). Interstitial lung fibrosis plays an important role in the pathogenesis of cor pulmonale: two thirds of the cases with interstitial lung fibrosis had developed cor pulmonale and all the cases with cor pulmonale also had interstitial lung fibrosis. Hypertensive arterial lesions of grade IV-VI according to Heath and Edwards (angiitis, plexogenic and angiomatoid lesions) have been described in severe cases of pulmonary hypertension (congenital cardiac shunts, primary pulmonary hypertension). In secondary forms of pulmonary hypertension, as represented by our material, these changes are of little importance."} {"id": "PMID:158874", "title": "Fasciola hepatica human infection. Histopathological study of sixteen cases.", "content": "Sixteen human cases of Fasciola hepatica infection are described. The liver was involved in 13 cases, the gall bladder in 9 cases and the stomach in 2 cases. Lesions containing parasitic remnants or fluke eggs were rarely seen. Surface scarring of the liver, scar tracks and granulomas within organs were the most characteristic changes seen and were the most useful for the histopathological diagnosis of the disease. The associated liver, bile and gastric lesions are briefly discussed.", "contents": "Fasciola hepatica human infection. Histopathological study of sixteen cases. Sixteen human cases of Fasciola hepatica infection are described. The liver was involved in 13 cases, the gall bladder in 9 cases and the stomach in 2 cases. Lesions containing parasitic remnants or fluke eggs were rarely seen. Surface scarring of the liver, scar tracks and granulomas within organs were the most characteristic changes seen and were the most useful for the histopathological diagnosis of the disease. The associated liver, bile and gastric lesions are briefly discussed."} {"id": "PMID:158875", "title": "Endocrine-amphicrine enteric carcinoma of the nasal mucosa.", "content": "A 39-year-old bus driver had been suffering for 2 years from a malignant polypoid mucosal proliferation of the upper nasal concha-ethmoid region, resembling a highly differentiated, villous-glandular adenocarcinoma of enteric type. There were numerous mono- and amphicrine cells and a massive quantity of oxyphilic, frequently Paneth-like goblet cells in the tumor. Immune-histochemically, a number of gastrin- and fewer glucagon-positive cells were identified. The somatostatin level in the serum was clearly increased. Electron-microscopically, 7 different endocrine cell types were identifiable, in order of decreasing frequency: A-like- and G-cells, both types of 5-HT-cells, A-cells, EG- and K-cell-like elements. Particularly impressive were the muco-argyrophilic amphicrine cells, containing A-granules. The unusual enteric character of the carcinoma seems to result from boundary movements and tissue displacements in an ecto-entodermal embryonic border region. There was no history of occupational wood dust inhalation.", "contents": "Endocrine-amphicrine enteric carcinoma of the nasal mucosa. A 39-year-old bus driver had been suffering for 2 years from a malignant polypoid mucosal proliferation of the upper nasal concha-ethmoid region, resembling a highly differentiated, villous-glandular adenocarcinoma of enteric type. There were numerous mono- and amphicrine cells and a massive quantity of oxyphilic, frequently Paneth-like goblet cells in the tumor. Immune-histochemically, a number of gastrin- and fewer glucagon-positive cells were identified. The somatostatin level in the serum was clearly increased. Electron-microscopically, 7 different endocrine cell types were identifiable, in order of decreasing frequency: A-like- and G-cells, both types of 5-HT-cells, A-cells, EG- and K-cell-like elements. Particularly impressive were the muco-argyrophilic amphicrine cells, containing A-granules. The unusual enteric character of the carcinoma seems to result from boundary movements and tissue displacements in an ecto-entodermal embryonic border region. There was no history of occupational wood dust inhalation."} {"id": "PMID:158876", "title": "Modifications in the sarcoplasmic reticulum and subcellular calcium distribution in skeletal muscle in a case of Westphal's disease (hypokalemic periodic paralysis).", "content": "In a case of hypokalemic periodic paralysis with characteristic alterations of the sarcoplasmic reticulum (SR) in the skeletal muscle, subcellular calcium re-partition, as revealed with the pyroantimonate technique, appears disturbed during paralysis. Pyroantimonate precipitates, normally concentrated in the terminal cisternae of the SR, were localized in the T tubules, whereas the terminal cisternae appeared empty. The increase (about 14%) in muscular calcium during paralysis may result from the accumulation of calcium in the extracellular compartment (T tubules). Defects in calcium uptake and storage by the SR may be involved in the pathogenesis of the periodic paralysis syndrome.", "contents": "Modifications in the sarcoplasmic reticulum and subcellular calcium distribution in skeletal muscle in a case of Westphal's disease (hypokalemic periodic paralysis). In a case of hypokalemic periodic paralysis with characteristic alterations of the sarcoplasmic reticulum (SR) in the skeletal muscle, subcellular calcium re-partition, as revealed with the pyroantimonate technique, appears disturbed during paralysis. Pyroantimonate precipitates, normally concentrated in the terminal cisternae of the SR, were localized in the T tubules, whereas the terminal cisternae appeared empty. The increase (about 14%) in muscular calcium during paralysis may result from the accumulation of calcium in the extracellular compartment (T tubules). Defects in calcium uptake and storage by the SR may be involved in the pathogenesis of the periodic paralysis syndrome."} {"id": "PMID:158877", "title": "Aberrant coronary artery in association with a quadricuspid pulmonary valve.", "content": "A case of quadricuspid pulmonary valve with an accessory coronary artery in an 82 year old woman is reported. This represents persistance of an early embryonic stage of development of the coronary circulation.", "contents": "Aberrant coronary artery in association with a quadricuspid pulmonary valve. A case of quadricuspid pulmonary valve with an accessory coronary artery in an 82 year old woman is reported. This represents persistance of an early embryonic stage of development of the coronary circulation."} {"id": "PMID:158885", "title": "Circulating suppressor cells in aplastic anemia.", "content": "In vitro proliferation and differentiation of hematopoietic stem cells was studied in a patient with aplastic anemia. Prior to therapy his peripheral blood contained a very low number of myeloid progenitors but a normal number of cells forming lymphoid colonies. Moreover, peripheral blood lymphocytes of this patient were able to suppress in vitro formation of myeloid colonies but not lymphoid colonies. This suppression effect was found to be sensitive to prednisolone and antithymocytic globulin. Following treatment with prednisolone, during which an apparent hematological recovery was observed, the level of lymphoid progenitors fell, but myeloid committed cells returned to normal and hematopoietic suppression was no longer detectable. These results indicate that cells suppressing hematopoiesis may circulate in the peripheral blood of some patients with aplastic anemia and the detection and testing of suceptibility of these cells to immunosuppressive drugs may be helpful in monitoring treatment and prognosis.", "contents": "Circulating suppressor cells in aplastic anemia. In vitro proliferation and differentiation of hematopoietic stem cells was studied in a patient with aplastic anemia. Prior to therapy his peripheral blood contained a very low number of myeloid progenitors but a normal number of cells forming lymphoid colonies. Moreover, peripheral blood lymphocytes of this patient were able to suppress in vitro formation of myeloid colonies but not lymphoid colonies. This suppression effect was found to be sensitive to prednisolone and antithymocytic globulin. Following treatment with prednisolone, during which an apparent hematological recovery was observed, the level of lymphoid progenitors fell, but myeloid committed cells returned to normal and hematopoietic suppression was no longer detectable. These results indicate that cells suppressing hematopoiesis may circulate in the peripheral blood of some patients with aplastic anemia and the detection and testing of suceptibility of these cells to immunosuppressive drugs may be helpful in monitoring treatment and prognosis."} {"id": "PMID:158883", "title": "[Effect of platinum and palladium compounds on mitochondrial enzymatic systems].", "content": "Effect of platinum and palladium complexes on respiration and ATPase activity in bovine heart tissue as well as on respiration of submitochondrial particles was studied. The highest inhibitory activity was exhibited by the complexes of platinum and palladium with pi-ligands in internal coorhdinational sphere such as ethylene-C H4, norbornadiene-C7H8 and allyl-C3H5. The electron density at the central atom of the complex was not responsible for the inhibitory affect of platinum and palladium on mitochondria.", "contents": "[Effect of platinum and palladium compounds on mitochondrial enzymatic systems]. Effect of platinum and palladium complexes on respiration and ATPase activity in bovine heart tissue as well as on respiration of submitochondrial particles was studied. The highest inhibitory activity was exhibited by the complexes of platinum and palladium with pi-ligands in internal coorhdinational sphere such as ethylene-C H4, norbornadiene-C7H8 and allyl-C3H5. The electron density at the central atom of the complex was not responsible for the inhibitory affect of platinum and palladium on mitochondria."} {"id": "PMID:158888", "title": "[The value of different investigation procedures in arterial hypertension (author's transl)].", "content": "221 patients with arterial hypertension were investigated as outpatients. 198 patients were found to have primary and 23 patients to have secondary hypertension. The results of urinary analysis were pathological in 25% of patients and renal function tests were abnormal in 20% of cases. Significant bacteriuria was recorded in 19% of urinary cultures. Intravenous pyelography showed true pathological findings in 12% of cases, false positive findings in 7% and false negative findings in 5%. Isotopic nephrograms showed true positive findings in 52%, false negative in 3% and 45% showed normal results. In 53% of patients angiography of the kidneys showed normal results, whilst this investigation proved pathological in 44% of cases and gave false negative results in 3% of patients. An additional search for coronary heart disease risk factors revealed that 73% of these hypertensive patients were overweight, 47% had hyperlipidaemia, 33% suffered from diabetes mellitus and nicotine abuse was present in 21% of cases. A relevant yet inexpensive screening programme for the investigation of hypertension is formulated on the basis of the results of this investigation.", "contents": "[The value of different investigation procedures in arterial hypertension (author's transl)]. 221 patients with arterial hypertension were investigated as outpatients. 198 patients were found to have primary and 23 patients to have secondary hypertension. The results of urinary analysis were pathological in 25% of patients and renal function tests were abnormal in 20% of cases. Significant bacteriuria was recorded in 19% of urinary cultures. Intravenous pyelography showed true pathological findings in 12% of cases, false positive findings in 7% and false negative findings in 5%. Isotopic nephrograms showed true positive findings in 52%, false negative in 3% and 45% showed normal results. In 53% of patients angiography of the kidneys showed normal results, whilst this investigation proved pathological in 44% of cases and gave false negative results in 3% of patients. An additional search for coronary heart disease risk factors revealed that 73% of these hypertensive patients were overweight, 47% had hyperlipidaemia, 33% suffered from diabetes mellitus and nicotine abuse was present in 21% of cases. A relevant yet inexpensive screening programme for the investigation of hypertension is formulated on the basis of the results of this investigation."} {"id": "PMID:158893", "title": "A viscosity model of polyacrylamide gel electrophoresis.", "content": "In current theories of polyacrylamide gel electrophoresis, the idea prevails that molecular sieving relies on different accessibility of volume fractions and of cross-sectional area fractions (denoted \"pores\") to different-sized ions due to the effect of \"geometric exclusion\". This correlates with the assumption that all elements of a polyacrylamide network occupy fixed and unchangeable positions thus forcing colliding macro-ions to diffuse laterally in order to find an \"accessible pore\" and to resume motion in direction of the electrical field. However, the alternative conception would be equally well justified, i.e. the assumption that polyacrylamide chains represent smooth obstacles cleared aside under the electrokinetic pressure of a macro-ion. This explanation would even be preferable with respect to the molecular sieving effects occurring in solutions of \"liquid polyacrylamide\". Yet no theory exists as to describe such effects in quantitative terms. In the present article, a parameter is defined and discussed, which can be estimated by experiment, and which seems to be apt to characterize local resistivity of polymer structures against dislocation and deformation: the \"fractional specific resistance\". Definition of this parameter is based on the model of a \"viscosity-emulsion\" composed of two interpenetrating liquid compartments which are characterized by different levels of hydrodynamic friction and the spatial dimensions of which are inferred from Ogston's theory. This concept of \"localized viscosity\" may also serve as a link between theories of molecular sieving and of \"macroscopic viscosity\" of flexible polymers. The data of Morris, formerly taken as verifications of the \"rigid-pore\" concept, are now interpreted in terms of four factors responsible for sizediscrimination: collision frequency, duration of single contacts, size-dependent frictional force, and the extent of cooperation among fibres, due to crosslinking and to simultanous contacts of several fibres to a single macro-ion. Some functions relevant for problems of molecular weight determination by gel electrophoresis are discussed in relation to the suggested model.", "contents": "A viscosity model of polyacrylamide gel electrophoresis. In current theories of polyacrylamide gel electrophoresis, the idea prevails that molecular sieving relies on different accessibility of volume fractions and of cross-sectional area fractions (denoted \"pores\") to different-sized ions due to the effect of \"geometric exclusion\". This correlates with the assumption that all elements of a polyacrylamide network occupy fixed and unchangeable positions thus forcing colliding macro-ions to diffuse laterally in order to find an \"accessible pore\" and to resume motion in direction of the electrical field. However, the alternative conception would be equally well justified, i.e. the assumption that polyacrylamide chains represent smooth obstacles cleared aside under the electrokinetic pressure of a macro-ion. This explanation would even be preferable with respect to the molecular sieving effects occurring in solutions of \"liquid polyacrylamide\". Yet no theory exists as to describe such effects in quantitative terms. In the present article, a parameter is defined and discussed, which can be estimated by experiment, and which seems to be apt to characterize local resistivity of polymer structures against dislocation and deformation: the \"fractional specific resistance\". Definition of this parameter is based on the model of a \"viscosity-emulsion\" composed of two interpenetrating liquid compartments which are characterized by different levels of hydrodynamic friction and the spatial dimensions of which are inferred from Ogston's theory. This concept of \"localized viscosity\" may also serve as a link between theories of molecular sieving and of \"macroscopic viscosity\" of flexible polymers. The data of Morris, formerly taken as verifications of the \"rigid-pore\" concept, are now interpreted in terms of four factors responsible for sizediscrimination: collision frequency, duration of single contacts, size-dependent frictional force, and the extent of cooperation among fibres, due to crosslinking and to simultanous contacts of several fibres to a single macro-ion. Some functions relevant for problems of molecular weight determination by gel electrophoresis are discussed in relation to the suggested model."} {"id": "PMID:158894", "title": "Inhibition of the nitrate reductase complex by dibromothymoquinone.", "content": "The plastoquinone antagonist 2,5-dibromothymoquinone was found to inhibit NO-3 reduction from NADH by the nitrate reductase complex from wheat. It accepts electrons from NADH through the NADH dehydrogenase activity of the nitrate reductase. However, it does not inhibit the reduction of 2,6-dichlorophenol-indophenol by the enzyme. This suggests that the two compounds may be accepting electrons at different places from the enzyme. Further it was observed that reduced DCIP could be oxidized by DBMIB in the absence of NADH indicating that the electron flow in the nitrate reductase complex may take place in a unidirectional way.", "contents": "Inhibition of the nitrate reductase complex by dibromothymoquinone. The plastoquinone antagonist 2,5-dibromothymoquinone was found to inhibit NO-3 reduction from NADH by the nitrate reductase complex from wheat. It accepts electrons from NADH through the NADH dehydrogenase activity of the nitrate reductase. However, it does not inhibit the reduction of 2,6-dichlorophenol-indophenol by the enzyme. This suggests that the two compounds may be accepting electrons at different places from the enzyme. Further it was observed that reduced DCIP could be oxidized by DBMIB in the absence of NADH indicating that the electron flow in the nitrate reductase complex may take place in a unidirectional way."} {"id": "PMID:158896", "title": "5-Methyltryptophan resistant cells of Catharanthus roseus.", "content": "Several cell lines resistant to 5-methyltryptophan were selected from wild type cells of different Catharanthus roseus suspension cultures. The resistant cells had up to 30 times the normal levels of free tryptophan. Despite the increased pool size of tryptophan anthranilate synthetase activity of resistant cells was as sensitive to inhibition by L-tryptophan as wild type cells. The overproduction of tryptophan did not lead to intensified accumulation of tryptamine nor of indole alkaloids. This was supported by a low conversion of tryptophan to tryptamine in vivo and in vitro. The overproduction of one of the primary precursors was evidently not sufficient to stimulate the rate of indole alkaloid synthesis in Catharanthus cells.", "contents": "5-Methyltryptophan resistant cells of Catharanthus roseus. Several cell lines resistant to 5-methyltryptophan were selected from wild type cells of different Catharanthus roseus suspension cultures. The resistant cells had up to 30 times the normal levels of free tryptophan. Despite the increased pool size of tryptophan anthranilate synthetase activity of resistant cells was as sensitive to inhibition by L-tryptophan as wild type cells. The overproduction of tryptophan did not lead to intensified accumulation of tryptamine nor of indole alkaloids. This was supported by a low conversion of tryptophan to tryptamine in vivo and in vitro. The overproduction of one of the primary precursors was evidently not sufficient to stimulate the rate of indole alkaloid synthesis in Catharanthus cells."} {"id": "PMID:158897", "title": "Complex influence of cytochalasin B on actin polymerization.", "content": "In the presence of very low concentrations (about 2X10(-7) M) of cytochalasin B (CB) the time course of actin polymerization is much more sigmoidal when followed by viscosity measurements than when followed by light scattering measurements. This suggests that under these conditions actin polymers do not immediately reach their final length but only via short \"bent\" polymers which can be detected only by light scattering but not by viscosity measurements. At higher CB concentrations (about equimolar to those of actin) CB reduces the average degree of polymerization and favors the nucleation step necessary for polymerization.", "contents": "Complex influence of cytochalasin B on actin polymerization. In the presence of very low concentrations (about 2X10(-7) M) of cytochalasin B (CB) the time course of actin polymerization is much more sigmoidal when followed by viscosity measurements than when followed by light scattering measurements. This suggests that under these conditions actin polymers do not immediately reach their final length but only via short \"bent\" polymers which can be detected only by light scattering but not by viscosity measurements. At higher CB concentrations (about equimolar to those of actin) CB reduces the average degree of polymerization and favors the nucleation step necessary for polymerization."} {"id": "PMID:158898", "title": "[Distribution and enzymic hypermethylation of inverted DNA repeats in different murine and human cells (author's transl)].", "content": "A specific class of DNA sequences, the inverted repetitive sequences, forms a double-stranded structure within a single linear polynucleotide chain in denatured DNA. The reassociation process is unimolecular and occurs very fast. Quantitative analyses have shown that these sequences comprise about 4--5% of the nuclear DNA of various mammalian cells (P815 mouse mastocytoma, Hela, L cells, Raji and Chang cells, and human embryonic hepatocytes) and are interspersed within sequences of other degrees of repetitiveness. After labeling the cells with L-[Methyl-3H]methionine and [14C]deoxycytidine, relative rates of enzymic DNA methylation were computed on the basis of 3H and 14C radioactivities found in pyrimidine residues of the nuclear DNA. The results indicate that DNA of inverted repetitive sequences is methylated to a level about 50% higher than the ordinary repetitive sequences and to about 300% higher than the unique and intermediary sequences. The biological function of the inverted repeats as well as the role of their enzymic hypermethylation is unknown.", "contents": "[Distribution and enzymic hypermethylation of inverted DNA repeats in different murine and human cells (author's transl)]. A specific class of DNA sequences, the inverted repetitive sequences, forms a double-stranded structure within a single linear polynucleotide chain in denatured DNA. The reassociation process is unimolecular and occurs very fast. Quantitative analyses have shown that these sequences comprise about 4--5% of the nuclear DNA of various mammalian cells (P815 mouse mastocytoma, Hela, L cells, Raji and Chang cells, and human embryonic hepatocytes) and are interspersed within sequences of other degrees of repetitiveness. After labeling the cells with L-[Methyl-3H]methionine and [14C]deoxycytidine, relative rates of enzymic DNA methylation were computed on the basis of 3H and 14C radioactivities found in pyrimidine residues of the nuclear DNA. The results indicate that DNA of inverted repetitive sequences is methylated to a level about 50% higher than the ordinary repetitive sequences and to about 300% higher than the unique and intermediary sequences. The biological function of the inverted repeats as well as the role of their enzymic hypermethylation is unknown."} {"id": "PMID:158899", "title": "[gamma-Irradiated ribosomes from Micrococcus radiodurans in a cell-free protein synthesizing system (author's transl)].", "content": "gamma-irradiation inactivation of isolated ribosomes of Micrococcus radiodurans was studied by examining poly U directed synthesis of polyphenylalanine. Ribosomes of M. radiodurans did not show significant gamma-radiation sensitivity up to a dose of approx. 11.6 k Gy. Cells of M. radiodurans take up more magnesium than E. coli cells unter the same conditions. The magnesium content of ribosomes of M. radiodurans was 18% higher than that of E. coli ribosomes. A possible relation between Mg2+-content and gamma-resistance is discussed.", "contents": "[gamma-Irradiated ribosomes from Micrococcus radiodurans in a cell-free protein synthesizing system (author's transl)]. gamma-irradiation inactivation of isolated ribosomes of Micrococcus radiodurans was studied by examining poly U directed synthesis of polyphenylalanine. Ribosomes of M. radiodurans did not show significant gamma-radiation sensitivity up to a dose of approx. 11.6 k Gy. Cells of M. radiodurans take up more magnesium than E. coli cells unter the same conditions. The magnesium content of ribosomes of M. radiodurans was 18% higher than that of E. coli ribosomes. A possible relation between Mg2+-content and gamma-resistance is discussed."} {"id": "PMID:158900", "title": "[Biological effects of electromagnetic fields (author's transl)].", "content": "This r\u00e9sum\u00e9 deals with thermal and nonthermal effects of electromagnetic fields on man. In consideration of two aspects a limitation is necessary. Firstly, there will be discussed only direct and immediate influences on biological cells and tissues, secondly, the treatment is limited to such phenomena, for which biophysical aproximations, based on experimental data, could be developed. Hazards for the human being may occur only by thermal effects within the microwave range. Regarding frequencies below approximately 30 kHz, excitation processes cannot be excluded in exceptional cases. Thermal effects are predominant, between 30 kHz and 100 kHz, before excitations can appear. Furthermore, by comparing the electrically and magnetically induced currents with the naturally flowing currents in man caused by the brain's and heart's electrical activity, a \"lower boundaryline\" was estimated. Regarding electric or magnetic field strengths undercutting this boundary-line, direct effects on the central nervous system may be excluded; other mechanisms should be responsible for demonstrated biological effects. The paper closes referring to some reports--presently discussed--on experimental findings of biological effects, which are observed as a result of the influence of electromagnetic fields of small field strengths.", "contents": "[Biological effects of electromagnetic fields (author's transl)]. This r\u00e9sum\u00e9 deals with thermal and nonthermal effects of electromagnetic fields on man. In consideration of two aspects a limitation is necessary. Firstly, there will be discussed only direct and immediate influences on biological cells and tissues, secondly, the treatment is limited to such phenomena, for which biophysical aproximations, based on experimental data, could be developed. Hazards for the human being may occur only by thermal effects within the microwave range. Regarding frequencies below approximately 30 kHz, excitation processes cannot be excluded in exceptional cases. Thermal effects are predominant, between 30 kHz and 100 kHz, before excitations can appear. Furthermore, by comparing the electrically and magnetically induced currents with the naturally flowing currents in man caused by the brain's and heart's electrical activity, a \"lower boundaryline\" was estimated. Regarding electric or magnetic field strengths undercutting this boundary-line, direct effects on the central nervous system may be excluded; other mechanisms should be responsible for demonstrated biological effects. The paper closes referring to some reports--presently discussed--on experimental findings of biological effects, which are observed as a result of the influence of electromagnetic fields of small field strengths."} {"id": "PMID:158901", "title": "Algal ferredoxin-NADP+ reductase with different molecular-weight forms.", "content": "Ferredoxin-NADP+ reductase from the microalga Bumilleriopsis was isolated by a combination of affinity chromatography on a flavodoxin-Sepharose 4 B column and usual purification procedures. Both the elution pattern of the final gel filtration step and of the sodium dodecylsulfate (SDS) disc gel electrophoresis indicate that there are at least two different molecular-weight forms of the reductase, a monomeric form and a dimeric one.", "contents": "Algal ferredoxin-NADP+ reductase with different molecular-weight forms. Ferredoxin-NADP+ reductase from the microalga Bumilleriopsis was isolated by a combination of affinity chromatography on a flavodoxin-Sepharose 4 B column and usual purification procedures. Both the elution pattern of the final gel filtration step and of the sodium dodecylsulfate (SDS) disc gel electrophoresis indicate that there are at least two different molecular-weight forms of the reductase, a monomeric form and a dimeric one."} {"id": "PMID:158902", "title": "A deterministic model for measles.", "content": "A deterministic model of recurrent epidemics is constructed using a non linear relationship between infection rate and number of contacts. Epidemic waves which are not damped are predicted and a relationship between community size and the period of recurrence is established. A possible explanation of measles outbreaks is suggested.", "contents": "A deterministic model for measles. A deterministic model of recurrent epidemics is constructed using a non linear relationship between infection rate and number of contacts. Epidemic waves which are not damped are predicted and a relationship between community size and the period of recurrence is established. A possible explanation of measles outbreaks is suggested."} {"id": "PMID:158903", "title": "[All-or-none behaviour and bistability in a simple cell model with autocatalysis of type A+2B = 3B (author's transl)].", "content": "Nonlinear kinetics in a chemical cell model involving only one substrate (A) and one product (B), two reactions (A yields B and A + 2B yields OB), and passive diffusion of A and B through the cell wall, can exhibit complex behaviour including oscillations, bistability (switching) and spiking. One such system is presented, which shows three kinds of response as depending on the quantity of a stimulus--a sudden imput of product B: i. no response; ii, spiking; iii, switching into an alternative steady state--i.e. an \"all-or flip-or-none\" response.", "contents": "[All-or-none behaviour and bistability in a simple cell model with autocatalysis of type A+2B = 3B (author's transl)]. Nonlinear kinetics in a chemical cell model involving only one substrate (A) and one product (B), two reactions (A yields B and A + 2B yields OB), and passive diffusion of A and B through the cell wall, can exhibit complex behaviour including oscillations, bistability (switching) and spiking. One such system is presented, which shows three kinds of response as depending on the quantity of a stimulus--a sudden imput of product B: i. no response; ii, spiking; iii, switching into an alternative steady state--i.e. an \"all-or flip-or-none\" response."} {"id": "PMID:158904", "title": "Phenylethylamine as a biochemical marker of tiger.", "content": "Pheromones of the tiger happen to be a mixture of amines which are \"fixed\" by lipids. One of these, found always in all the four tigers investigated, is phenylethylamine. This may be a biochemical marker at a species level.", "contents": "Phenylethylamine as a biochemical marker of tiger. Pheromones of the tiger happen to be a mixture of amines which are \"fixed\" by lipids. One of these, found always in all the four tigers investigated, is phenylethylamine. This may be a biochemical marker at a species level."} {"id": "PMID:158908", "title": "[Development of gingival inflammations in schoolchildren instructed in proper oral hygiene in a seven-year longitudinal study conducted under clinically controlled conditions and as part of the Preventive Stomatology research project (author's transl)].", "content": "Instruction of six- and seven-year-old children (N = 1167) at the beginning of this longitudinal study was given by a stomatological nurse at weekly intervals and, later, at fortnightly and monthly intervals, respectively. Compared with a group of untreated controls were not only those children who were instructed in proper oral hygiene but children receiving additional doses of amine fluorides as well. During the seven-year period of observation there was noted a distinct improvement in oral hygiene (OHI) as well as a reduction of gingival inflammations (PM index). Whereas additional administration of amine fluorides had no appreciable effect upon both oral hygiene and the condition of health of the gingiva there was a direct relation to the frequency of instructions in oral hygiene at school.", "contents": "[Development of gingival inflammations in schoolchildren instructed in proper oral hygiene in a seven-year longitudinal study conducted under clinically controlled conditions and as part of the Preventive Stomatology research project (author's transl)]. Instruction of six- and seven-year-old children (N = 1167) at the beginning of this longitudinal study was given by a stomatological nurse at weekly intervals and, later, at fortnightly and monthly intervals, respectively. Compared with a group of untreated controls were not only those children who were instructed in proper oral hygiene but children receiving additional doses of amine fluorides as well. During the seven-year period of observation there was noted a distinct improvement in oral hygiene (OHI) as well as a reduction of gingival inflammations (PM index). Whereas additional administration of amine fluorides had no appreciable effect upon both oral hygiene and the condition of health of the gingiva there was a direct relation to the frequency of instructions in oral hygiene at school."} {"id": "PMID:158909", "title": "[The systemic circulation and microcirculation of the periodontium vital microscopy and histological studies of incisors of rats (author's transl)].", "content": "A new classification of the angioarchitecture and blood flow is proposed in light of the results of vital microscopy studies of the windowed periodontium and gingiva of the incisors of rats. The flow pattern and the rate of blood flow are different in different vessels. The flow of blood in segmented and interconnected arterial and venous vascular sections in the alveolar and marginal periodontium corresponds to what is known as systemic circulation, whereas that in arterioles, capillaries, and venoles must be considered as belonging to what is referred to as microcirculation. Subepithelially, the microcirculatory elements constitute a nutritive, typically ordered capillary network as contrasted with the random spatial arrangement of capillary loops in the alveolar periodontium. Numerous anastomoses provide the basis for possible functional adaptation, leading to the formation of polygonal ring closures in the alveolar region. The interpretations of functional findings are based upon histotopological reexaminations.", "contents": "[The systemic circulation and microcirculation of the periodontium vital microscopy and histological studies of incisors of rats (author's transl)]. A new classification of the angioarchitecture and blood flow is proposed in light of the results of vital microscopy studies of the windowed periodontium and gingiva of the incisors of rats. The flow pattern and the rate of blood flow are different in different vessels. The flow of blood in segmented and interconnected arterial and venous vascular sections in the alveolar and marginal periodontium corresponds to what is known as systemic circulation, whereas that in arterioles, capillaries, and venoles must be considered as belonging to what is referred to as microcirculation. Subepithelially, the microcirculatory elements constitute a nutritive, typically ordered capillary network as contrasted with the random spatial arrangement of capillary loops in the alveolar periodontium. Numerous anastomoses provide the basis for possible functional adaptation, leading to the formation of polygonal ring closures in the alveolar region. The interpretations of functional findings are based upon histotopological reexaminations."} {"id": "PMID:158910", "title": "[The effect of aging upon the size of cell nuclei of the spinous layer in the bony palate and cheek of man (author's transl)].", "content": "The volumes of the cell nuclei of the spinous layer of the human oral mucosa show considerable variations in dependence upon both the process of aging and the cellular metabolism. The differences in the mean volumes of cell nuclei are fairly large for the bony palate as well as the cheek, and statistical evidence has been obtained for these. Stomatologically, this investigation may be regarded as having broken new ground and will add to our understanding of the aging of human organs of mastication.", "contents": "[The effect of aging upon the size of cell nuclei of the spinous layer in the bony palate and cheek of man (author's transl)]. The volumes of the cell nuclei of the spinous layer of the human oral mucosa show considerable variations in dependence upon both the process of aging and the cellular metabolism. The differences in the mean volumes of cell nuclei are fairly large for the bony palate as well as the cheek, and statistical evidence has been obtained for these. Stomatologically, this investigation may be regarded as having broken new ground and will add to our understanding of the aging of human organs of mastication."} {"id": "PMID:158911", "title": "[On the clinical aspects and ultrastructure of bullous pemphigoid (parapemphigus) of the oral mucous membrane (author's transl)].", "content": "Bullous changes in the oral mucosa are often the first signs of a general dermatological disease. Successful diagnosis of such diseases is largely dependent upon the use of complex laboratory methods. Clinical and ultrastructural changes are described and discussed with particular reference to a case of parapemphigus. Atypical intracellular vacuolation and marked acantholysis observed in electron micrographs is interpreted as a secondary phenomenon of direct blistering.", "contents": "[On the clinical aspects and ultrastructure of bullous pemphigoid (parapemphigus) of the oral mucous membrane (author's transl)]. Bullous changes in the oral mucosa are often the first signs of a general dermatological disease. Successful diagnosis of such diseases is largely dependent upon the use of complex laboratory methods. Clinical and ultrastructural changes are described and discussed with particular reference to a case of parapemphigus. Atypical intracellular vacuolation and marked acantholysis observed in electron micrographs is interpreted as a secondary phenomenon of direct blistering."} {"id": "PMID:158907", "title": "[Effect of a decrease in brain noradrenaline and serotonin levels on defensive and food-getting conditioned reflexes in rats].", "content": "The influence of pharmacological and surgical interferences in the activity of serotoninergic and catecholaminergic brain systems on elaboration and consolidation of conditioned reflexes was studied in rats. Ablation of the locus coeruleus, nucleus raphe and administration of inhibitors of monoamines synthesis reduced noradrenaline and serotonin (5-OT) content in rat's brain. Ablation of the locus coeruleus and disulphiram administration impaired mainly the elaboration of defensive and alimentary conditioned reflexes. Ablation of the nucleus raphe and parachlorphenilalanin administration affected predominantly the retention of the reflexes. At the same time, the effects of surgical and pharmacological interferences differed in some respects", "contents": "[Effect of a decrease in brain noradrenaline and serotonin levels on defensive and food-getting conditioned reflexes in rats]. The influence of pharmacological and surgical interferences in the activity of serotoninergic and catecholaminergic brain systems on elaboration and consolidation of conditioned reflexes was studied in rats. Ablation of the locus coeruleus, nucleus raphe and administration of inhibitors of monoamines synthesis reduced noradrenaline and serotonin (5-OT) content in rat's brain. Ablation of the locus coeruleus and disulphiram administration impaired mainly the elaboration of defensive and alimentary conditioned reflexes. Ablation of the nucleus raphe and parachlorphenilalanin administration affected predominantly the retention of the reflexes. At the same time, the effects of surgical and pharmacological interferences differed in some respects"} {"id": "PMID:158912", "title": "[Experiences obtained with the use of schulte's diagnostic program in myoarthropathies (author's transl)].", "content": "Using Schulte's diagnostic and therapeutic system of treating the pain-dysfunction syndrome, 165 patients were included in a program of myogymnastic self-treatment. The results obtained on reexamination of 96 patients confirmed the correlations observed by Schulte between the principal symptoms (painful side and lateral deviation of the lower jaw) and numerous causal factors. The diagnostic schemes used to search for causal factors may thus be regarded as having proved successful. They allow functional temporomandibular complaints to be classed in groups of diseases by taking into account the principal symptoms alone, namely, painful side and deviation of the lower jaw upon opening the mouth.", "contents": "[Experiences obtained with the use of schulte's diagnostic program in myoarthropathies (author's transl)]. Using Schulte's diagnostic and therapeutic system of treating the pain-dysfunction syndrome, 165 patients were included in a program of myogymnastic self-treatment. The results obtained on reexamination of 96 patients confirmed the correlations observed by Schulte between the principal symptoms (painful side and lateral deviation of the lower jaw) and numerous causal factors. The diagnostic schemes used to search for causal factors may thus be regarded as having proved successful. They allow functional temporomandibular complaints to be classed in groups of diseases by taking into account the principal symptoms alone, namely, painful side and deviation of the lower jaw upon opening the mouth."} {"id": "PMID:158913", "title": "[Method of measuring soft part pressures in the oral cavity (author's transl)].", "content": "For measuring static and dynamic soft part pressures within the oral cavity, it is necessary to use specialized transducers and a suitable measuring method. The design of strain gage type pressure measuring probes is descirbed and problems of calibration and elimination of measurement errors are discussed.", "contents": "[Method of measuring soft part pressures in the oral cavity (author's transl)]. For measuring static and dynamic soft part pressures within the oral cavity, it is necessary to use specialized transducers and a suitable measuring method. The design of strain gage type pressure measuring probes is descirbed and problems of calibration and elimination of measurement errors are discussed."} {"id": "PMID:158914", "title": "[On the determination of Gm(1) in hard dental tissue (author's transl)].", "content": "Tests for the presence of Gm(1) substance were made on a total of 104 human teeth. In about 90 percent of the cases examined, it was possible to observe agreement between the serum and the Gm(1) substance. Lack of eluted dental material and a high degree of affection with caries were found to have adverse effects upon Gm(1) typification. Detection of the Gm(1) substance is another important characteristic in forensic identification.", "contents": "[On the determination of Gm(1) in hard dental tissue (author's transl)]. Tests for the presence of Gm(1) substance were made on a total of 104 human teeth. In about 90 percent of the cases examined, it was possible to observe agreement between the serum and the Gm(1) substance. Lack of eluted dental material and a high degree of affection with caries were found to have adverse effects upon Gm(1) typification. Detection of the Gm(1) substance is another important characteristic in forensic identification."} {"id": "PMID:158917", "title": "[Importance of laparoscopy to postoperative treatment of ovarian carcinoma (author's transl)].", "content": "Indications in favour of peritoneoscopy in postoperative after-treatment of ovarian carcinomas are proposed on the basis of the authors' own experience. Postoperative laparoscopy in combination with peritoneal cytology and histology appears to be justified in support of differentiated postoperative therapy, since it enables modification of empirical and rigid decions for high-continuity after-treatment of ovarian carcinomas.", "contents": "[Importance of laparoscopy to postoperative treatment of ovarian carcinoma (author's transl)]. Indications in favour of peritoneoscopy in postoperative after-treatment of ovarian carcinomas are proposed on the basis of the authors' own experience. Postoperative laparoscopy in combination with peritoneal cytology and histology appears to be justified in support of differentiated postoperative therapy, since it enables modification of empirical and rigid decions for high-continuity after-treatment of ovarian carcinomas."} {"id": "PMID:158923", "title": "[Incidence of neurologic diseases in children].", "content": "Data concerning the distribution and the nosological structure of nervous diseases in children aged from one month to 14 years in the town of N. (76 thousand inhabitants, 16,716 children) are presented. Peculiarities of the dynamics of the disease entities with reference to the age, as well as the influence of the sex on the disease entity are shown. Ranging of the distribution data has made it possible to fix the principal rank places for individual disease entities. The data obtained served as basis for calculating the requirements for neurological beds in children's hospitals and other specialized medical institutions for children.", "contents": "[Incidence of neurologic diseases in children]. Data concerning the distribution and the nosological structure of nervous diseases in children aged from one month to 14 years in the town of N. (76 thousand inhabitants, 16,716 children) are presented. Peculiarities of the dynamics of the disease entities with reference to the age, as well as the influence of the sex on the disease entity are shown. Ranging of the distribution data has made it possible to fix the principal rank places for individual disease entities. The data obtained served as basis for calculating the requirements for neurological beds in children's hospitals and other specialized medical institutions for children."} {"id": "PMID:158924", "title": "[Health resort treatment of children with progressive muscular dystrophy].", "content": "The results of a complex treatment at health resorts of 126 children with Duchenne myopathy and 84 children with spinal amyotrophies at the age of 5-15 years are given. The complexes included carbon-dioxide sulfurated hydrogen baths, mud application (with different localization depending on a form of the disease), fresh baths, oxygenotherapy and therapeutic physical training. The authors revealed good tolerance to procedures and the positive dynamics of the main clinical manifestations of the disease, confirmed by the electrophysiological and biochemical studies. As a result of the treatment it was possible to achieve progressiveness of the disease in all patients at different periods (from 1 month to 1 year). The authors give recommendations for the use of treatment at health resorts as a necessary link in the general chain of rehabilitative measures for children with various forms of progressive muscular dystrophies.", "contents": "[Health resort treatment of children with progressive muscular dystrophy]. The results of a complex treatment at health resorts of 126 children with Duchenne myopathy and 84 children with spinal amyotrophies at the age of 5-15 years are given. The complexes included carbon-dioxide sulfurated hydrogen baths, mud application (with different localization depending on a form of the disease), fresh baths, oxygenotherapy and therapeutic physical training. The authors revealed good tolerance to procedures and the positive dynamics of the main clinical manifestations of the disease, confirmed by the electrophysiological and biochemical studies. As a result of the treatment it was possible to achieve progressiveness of the disease in all patients at different periods (from 1 month to 1 year). The authors give recommendations for the use of treatment at health resorts as a necessary link in the general chain of rehabilitative measures for children with various forms of progressive muscular dystrophies."} {"id": "PMID:158925", "title": "[Health resort treatment of preschool children with cerebral palsy].", "content": "In the Pyatigorsk resort, 226 children from 3-7 years of age with different forms of cerebral paralysis were studied. For therapeutic purposes, besides general health improvement measures, remedial gymnastic and massage, such resort factors as carbon dioxide and sulfurated hydrogen and radon baths of different concentrations and mud procedures were used. As a result of such studies, some indications for referrals of preschool children with cerebral paralysis to balneomud resorts were outlined. Differentiated complexes of resort treatment, depending upon the form and severity of clinical sings were elaborated, as well as the possibility of resort therapy in children with cerebral paralysis, complicated by the intracranial hypertensive syndrome.", "contents": "[Health resort treatment of preschool children with cerebral palsy]. In the Pyatigorsk resort, 226 children from 3-7 years of age with different forms of cerebral paralysis were studied. For therapeutic purposes, besides general health improvement measures, remedial gymnastic and massage, such resort factors as carbon dioxide and sulfurated hydrogen and radon baths of different concentrations and mud procedures were used. As a result of such studies, some indications for referrals of preschool children with cerebral paralysis to balneomud resorts were outlined. Differentiated complexes of resort treatment, depending upon the form and severity of clinical sings were elaborated, as well as the possibility of resort therapy in children with cerebral paralysis, complicated by the intracranial hypertensive syndrome."} {"id": "PMID:158927", "title": "[Immunoglobulin and lysozyme concentration in the serum of patients with Down's syndrome].", "content": "A study of the immunoglobulin level in the 3 main classes (IgG, IgM and IgA) and lysozymes in the blood serum of 73 patients with Down's disease (from 5 to 20 years of age) showed an increase of IgG in the younger age (up to 7 years) and older groups (over 7 years). The content of IgM was significantly lower in the younger group and did not differ from the control indices in the older group. The level of IgA corresponded to normal indices. The studies demonstrated a marked drop in the lysozyme content. The role of the abnormal system of humoral immunity and reactions of nonspecific defense in the formation of predisposition to the development of infectious diseases in this form of pathology is discussed.", "contents": "[Immunoglobulin and lysozyme concentration in the serum of patients with Down's syndrome]. A study of the immunoglobulin level in the 3 main classes (IgG, IgM and IgA) and lysozymes in the blood serum of 73 patients with Down's disease (from 5 to 20 years of age) showed an increase of IgG in the younger age (up to 7 years) and older groups (over 7 years). The content of IgM was significantly lower in the younger group and did not differ from the control indices in the older group. The level of IgA corresponded to normal indices. The studies demonstrated a marked drop in the lysozyme content. The role of the abnormal system of humoral immunity and reactions of nonspecific defense in the formation of predisposition to the development of infectious diseases in this form of pathology is discussed."} {"id": "PMID:158930", "title": "Skin necrosis between parallel abdominal incisions.", "content": "Four cases of skin necrosis between vertical abdominal incisions are presented. Even though many years may elapse between the abdominal operations, necrosis of the skin as well as of the underlying fascia may develop between new and old vertical incisions parallel with each other. Such necrosis probably takes place particularly in patients with impaired peripheral circulation.", "contents": "Skin necrosis between parallel abdominal incisions. Four cases of skin necrosis between vertical abdominal incisions are presented. Even though many years may elapse between the abdominal operations, necrosis of the skin as well as of the underlying fascia may develop between new and old vertical incisions parallel with each other. Such necrosis probably takes place particularly in patients with impaired peripheral circulation."} {"id": "PMID:158931", "title": "Use of a new laser Doppler flowmeter for measurement of capillary blood flow in skeletal muscle after bullet wounding.", "content": "A new instrument for measurement of regional muscle blood flow based on the laser Doppler principle is described. The method has been used to determine blood flow in skeletal muscle of pigs after bullet wounding. This new method constitutes a promising technique for non-invasive blood flow measurements in superficial layers of skin and muscle.", "contents": "Use of a new laser Doppler flowmeter for measurement of capillary blood flow in skeletal muscle after bullet wounding. A new instrument for measurement of regional muscle blood flow based on the laser Doppler principle is described. The method has been used to determine blood flow in skeletal muscle of pigs after bullet wounding. This new method constitutes a promising technique for non-invasive blood flow measurements in superficial layers of skin and muscle."} {"id": "PMID:158932", "title": "[The use of N,N'-diethylpseudoisocyaninchloride for the polarization optical detection of polyanions in the histological section (author's transl)].", "content": "In the paper a technique of the polarization optical qualitative and quantitative detection of polyanions with N,N'-diethylpseudoisocyaninchloride in the histological section is described. It is possible to prevent depolymerisation after precipitation with potassium ferricyanide and to intensify the birefringence of the histological structures. In vitro attempts and measurements of the dispersion of the double refraction and of the dichroism indicate connections between the optical appearances, furthermore it is possible to make statements about the mechanism of the arrangement of the tissue-dye-ferricyanide-complex.", "contents": "[The use of N,N'-diethylpseudoisocyaninchloride for the polarization optical detection of polyanions in the histological section (author's transl)]. In the paper a technique of the polarization optical qualitative and quantitative detection of polyanions with N,N'-diethylpseudoisocyaninchloride in the histological section is described. It is possible to prevent depolymerisation after precipitation with potassium ferricyanide and to intensify the birefringence of the histological structures. In vitro attempts and measurements of the dispersion of the double refraction and of the dichroism indicate connections between the optical appearances, furthermore it is possible to make statements about the mechanism of the arrangement of the tissue-dye-ferricyanide-complex."} {"id": "PMID:158933", "title": "[Cellular immune reactivity in patients with multiple myeloma].", "content": "The ConA-, PHA- and PWM-induced lymphocyte transformation rates were significantly decreased in 19 patients with multiple myeloma. Lymphocyte-inherent defects rather than serum factors seem to account for this decreased lymphocyte reactivity. In 58% of the patients a pathologically increased ConA-induced suppressor cell activity, which was negatively correlated with the non-paraprotein IgM-concentration, was found.", "contents": "[Cellular immune reactivity in patients with multiple myeloma]. The ConA-, PHA- and PWM-induced lymphocyte transformation rates were significantly decreased in 19 patients with multiple myeloma. Lymphocyte-inherent defects rather than serum factors seem to account for this decreased lymphocyte reactivity. In 58% of the patients a pathologically increased ConA-induced suppressor cell activity, which was negatively correlated with the non-paraprotein IgM-concentration, was found."} {"id": "PMID:158934", "title": "Cerebrospinal fluid protein findings in various lower back pain syndromes.", "content": "Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations.", "contents": "Cerebrospinal fluid protein findings in various lower back pain syndromes. Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations."} {"id": "PMID:158935", "title": "Posterior fusion of the lumbosacral spine. Evaluation of the operative results and the factors influencing them.", "content": "The operative results of 79 patients subjected to posterior fusion of the lumbosacral spine were evaluated on the basis of a follow-up examination performed on average 5.4 years after operation. A method of evaluation was developed which measured the patients' subjective improvement and working capacity. The method proved appropriate for clinical use and gave a more correct picture of the operative result than methods relying on the patients' own opinion or the radiographic assessment as the only criterion. Sixty per cent of the patients were subjectively improved, 40 per cent had returned to their previous or a corresponding occupation and 24 per cent had a good operative result, assessed by the method applied. A statistical analysis was performed in order to find the factors influencing the operative results. Age over 40 years, heavy or moderately heavy preoperative work and over 6 months' preoperative disability had a statistically significant, unfavourable effect on the results. In the case of labourers in heavy occupations, working capacity was seldom restored to a degree sufficient for return to their previous work. The operative technique proved reliable with 91 per cent successful fusions, assessed from functional radiographs. Successful fusion did not imply a good operative result, although it did so more often than non-fusion. On the basis of this study, operative fusion of the lumbosacral spine seems to be of relatively little value in the treatment of patients suffering from low back pain, and factors other than purely medical or surgical have a considerable influence on the operative results.", "contents": "Posterior fusion of the lumbosacral spine. Evaluation of the operative results and the factors influencing them. The operative results of 79 patients subjected to posterior fusion of the lumbosacral spine were evaluated on the basis of a follow-up examination performed on average 5.4 years after operation. A method of evaluation was developed which measured the patients' subjective improvement and working capacity. The method proved appropriate for clinical use and gave a more correct picture of the operative result than methods relying on the patients' own opinion or the radiographic assessment as the only criterion. Sixty per cent of the patients were subjectively improved, 40 per cent had returned to their previous or a corresponding occupation and 24 per cent had a good operative result, assessed by the method applied. A statistical analysis was performed in order to find the factors influencing the operative results. Age over 40 years, heavy or moderately heavy preoperative work and over 6 months' preoperative disability had a statistically significant, unfavourable effect on the results. In the case of labourers in heavy occupations, working capacity was seldom restored to a degree sufficient for return to their previous work. The operative technique proved reliable with 91 per cent successful fusions, assessed from functional radiographs. Successful fusion did not imply a good operative result, although it did so more often than non-fusion. On the basis of this study, operative fusion of the lumbosacral spine seems to be of relatively little value in the treatment of patients suffering from low back pain, and factors other than purely medical or surgical have a considerable influence on the operative results."} {"id": "PMID:158936", "title": "The state of health of Swedish children.", "content": "An attempt is made briefly to describe the present health problems of Swedish children. The report is based on data available in official statistics or collected from special studies. It is concluded that the general state of health of Swedish children is good when assessed by commonly used criteria. The mortality pattern is dominated by perinatal and accidental deaths, but also neoplasms are of importance. There are indications that genetic and handicapping disorders, and psychosocial maladjustment will receive more attention in the future.", "contents": "The state of health of Swedish children. An attempt is made briefly to describe the present health problems of Swedish children. The report is based on data available in official statistics or collected from special studies. It is concluded that the general state of health of Swedish children is good when assessed by commonly used criteria. The mortality pattern is dominated by perinatal and accidental deaths, but also neoplasms are of importance. There are indications that genetic and handicapping disorders, and psychosocial maladjustment will receive more attention in the future."} {"id": "PMID:158937", "title": "Socio-economic status of the family and health problems in the preschool child. Lack of correlation in a Swedish sample.", "content": "Recent reports from countries with a highly developed economic status point out the association of well-being of children with socio-economic factors. The aim of the present investigation was to examine the extent to which health problems, i.e. functional impairments, diseases and handicaps, in 4-year-old children are related to socio-economic factors. The analysis was based on data from 7 173 children who had undergone the routine general health screening of 4-year-olds in the county of Uppsala. In the statistical analysis the main emphasis was laid on an explanation of the variance on the individual plane. The results showed that the correlations between health problems and socio-economic factors in general were weak or non-existent. An explanation of the lack of correlation in our sample might be that Sweden had succeeded in largely eliminating the health problems associated with external living conditions of the family. If differences between population groups do exist--and in the light of findings from other investigations it seems highly probable that they do--then these differences are probably to be sought in families' way of functioning, in the internal and external pattern of communication, in the general emotional climate and in the degree of social integration in the society.", "contents": "Socio-economic status of the family and health problems in the preschool child. Lack of correlation in a Swedish sample. Recent reports from countries with a highly developed economic status point out the association of well-being of children with socio-economic factors. The aim of the present investigation was to examine the extent to which health problems, i.e. functional impairments, diseases and handicaps, in 4-year-old children are related to socio-economic factors. The analysis was based on data from 7 173 children who had undergone the routine general health screening of 4-year-olds in the county of Uppsala. In the statistical analysis the main emphasis was laid on an explanation of the variance on the individual plane. The results showed that the correlations between health problems and socio-economic factors in general were weak or non-existent. An explanation of the lack of correlation in our sample might be that Sweden had succeeded in largely eliminating the health problems associated with external living conditions of the family. If differences between population groups do exist--and in the light of findings from other investigations it seems highly probable that they do--then these differences are probably to be sought in families' way of functioning, in the internal and external pattern of communication, in the general emotional climate and in the degree of social integration in the society."} {"id": "PMID:158938", "title": "Enzyme histochemistry of non-Hodgkin's lymphomas.", "content": "Fifty-two cases of non-Hodgkin's lymphomas were studied with enzyme histochemical methods. Forty-four cases of these were also investigated for surface markers with immunological techniques, and results of histochemical, routine histological and immunological observations were correlated. Twenty-one of 27 B-cell lymphomas showed prominent ATPase activity, while all 13 T-cell lymphomas, except one case, did not show such activity. Nodular lymphomas, though of B-cell nature, were often negative for ATPase and it remained negative after diffuse evolution in some. Four of 7 A1Pase positive lymphomas were of B-cell origin. Dot-like localized AcPase and beta-glucuronidase activity characterized T-cell lymphomas while 5 T-cell PDL, including lymphoblastic type with double markers, showed localized esterase activity. Enzyme histochemical characteristics of lymphomas were fairly honest reflection of those of various functional units in the normal lymph nodes. Enzyme histochemical methods appeared to be a useful tool for the study of lymphomas.", "contents": "Enzyme histochemistry of non-Hodgkin's lymphomas. Fifty-two cases of non-Hodgkin's lymphomas were studied with enzyme histochemical methods. Forty-four cases of these were also investigated for surface markers with immunological techniques, and results of histochemical, routine histological and immunological observations were correlated. Twenty-one of 27 B-cell lymphomas showed prominent ATPase activity, while all 13 T-cell lymphomas, except one case, did not show such activity. Nodular lymphomas, though of B-cell nature, were often negative for ATPase and it remained negative after diffuse evolution in some. Four of 7 A1Pase positive lymphomas were of B-cell origin. Dot-like localized AcPase and beta-glucuronidase activity characterized T-cell lymphomas while 5 T-cell PDL, including lymphoblastic type with double markers, showed localized esterase activity. Enzyme histochemical characteristics of lymphomas were fairly honest reflection of those of various functional units in the normal lymph nodes. Enzyme histochemical methods appeared to be a useful tool for the study of lymphomas."} {"id": "PMID:158939", "title": "Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. III. Changes in the areal density of cytoplasmic vacuoles containing endocytized Thorotrast.", "content": "H-2b lymphocytes were sensitized against H-2d alloantigens by a lymphocyte culture reaction (MLR) and incubated with H-2d mastocytoma cells. Thirty minutes before incubation with the mastocytoma cells Thorotrast was added to the lymphocyte culture medium. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal densities of the cytoplasmic vacuoles were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed changes following interaction with target cells. The areal density of Thorotrast containing vacuoles in sensitized lymphoblasts increased during the three hour observation period, but the percentage of vacuoles containing Thorotrast in the total area of cytoplasmic vacuoles decreased in the first thirty minutes of interaction with target cells. This observation may indicate greater formation of vacuoles from the Golgi apparatus compared with the formation of vacuoles from the cytoplasmic membrane at the onset of interaction with target cells. In the multivesicular bodies (MVB) the Thorotrast was first observed inside the small vesicles and later on it was also observed in the matrix of the MVB. After three hours of interaction Thorotrast was observed laying \"free\" in the matrix of phagosomes along with myelin figures.", "contents": "Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. III. Changes in the areal density of cytoplasmic vacuoles containing endocytized Thorotrast. H-2b lymphocytes were sensitized against H-2d alloantigens by a lymphocyte culture reaction (MLR) and incubated with H-2d mastocytoma cells. Thirty minutes before incubation with the mastocytoma cells Thorotrast was added to the lymphocyte culture medium. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal densities of the cytoplasmic vacuoles were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed changes following interaction with target cells. The areal density of Thorotrast containing vacuoles in sensitized lymphoblasts increased during the three hour observation period, but the percentage of vacuoles containing Thorotrast in the total area of cytoplasmic vacuoles decreased in the first thirty minutes of interaction with target cells. This observation may indicate greater formation of vacuoles from the Golgi apparatus compared with the formation of vacuoles from the cytoplasmic membrane at the onset of interaction with target cells. In the multivesicular bodies (MVB) the Thorotrast was first observed inside the small vesicles and later on it was also observed in the matrix of the MVB. After three hours of interaction Thorotrast was observed laying \"free\" in the matrix of phagosomes along with myelin figures."} {"id": "PMID:158941", "title": "Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex.", "content": "Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05-0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57 +/- (S.D.) 1.73 ml/min.g, and 4.35 +/- 0.57 ml/min.g, which is higher than found using 0.2-0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.", "contents": "Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex. Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05-0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57 +/- (S.D.) 1.73 ml/min.g, and 4.35 +/- 0.57 ml/min.g, which is higher than found using 0.2-0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow."} {"id": "PMID:158942", "title": "RNA synthesis in permeable mouse ascites sarcoma cells.", "content": "A permeable cell system for studying RNA synthesis was established. Mouse ascites sarcoma cells were made permeable to nucleoside triphosphates and alpha-amanitin by treating with a hypotonic buffer. Separate determinations of endogenous RNA polymerase I, II and III activities in permeable cells were conducted using the different sensitivities of these enzymes to alpha-amanitin. The endogenous activity of RNA polymerase II under optimal conditions was one tenth of total RNA synthetic activity in isolated nuclei, and one third of that in permeable cells. The extremely low ratio of RNA polymerase II activity to total RNA synthetic activity in isolated nuclei was thought to be caused by increase of RNA polymerase I activity and decrease of RNA polymerase II activity. These and other results suggested that RNA synthesis in permeable cells reflects more precisely the in vivo state of RNA synthesis than thatin isolated nuclei. The permeable cell system will provide a useful method for studying the separate activities of RNA polymerases I, II and III in situ.", "contents": "RNA synthesis in permeable mouse ascites sarcoma cells. A permeable cell system for studying RNA synthesis was established. Mouse ascites sarcoma cells were made permeable to nucleoside triphosphates and alpha-amanitin by treating with a hypotonic buffer. Separate determinations of endogenous RNA polymerase I, II and III activities in permeable cells were conducted using the different sensitivities of these enzymes to alpha-amanitin. The endogenous activity of RNA polymerase II under optimal conditions was one tenth of total RNA synthetic activity in isolated nuclei, and one third of that in permeable cells. The extremely low ratio of RNA polymerase II activity to total RNA synthetic activity in isolated nuclei was thought to be caused by increase of RNA polymerase I activity and decrease of RNA polymerase II activity. These and other results suggested that RNA synthesis in permeable cells reflects more precisely the in vivo state of RNA synthesis than thatin isolated nuclei. The permeable cell system will provide a useful method for studying the separate activities of RNA polymerases I, II and III in situ."} {"id": "PMID:158943", "title": "Effects of some polyamines, polyanions and antitumor drugs on replicative DNA synthesis and unscheduled DNA synthesis in vitro.", "content": "The effects of various compounds on replicative DNA synthesis in permeable mouse ascites sarcoma cells and on unscheduled DNA synthesis in permeable cells or in isolated rat liver nuclei were studied. Polyamines such as spermidine, putrescine and cadaverine inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by spermidine and cadaverine, but slightly stimulated by putrescine at low concentrations. Aurintricarboxylic acid, a low molecular weight polyanion, inhibited both replicative DNA synthesis and unscheduled DNA synthesis. Replicative DNA synthesis was inhibited by heparin, a high molecular weight polyanion, whereas unscheduled DNA synthesis was stimulated at low heparin concentrations. Antitumor drugs such as daunomycin, neocarzinostatin and bleomycin inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by daunomycin, slightly induced by neocarzinostatin and highly induced by bleomycin. The present system was thought to be useful for studying the separate effects of various drugs on either replicative DNA synthesis or unscheduled DNA synthesis in vitro.", "contents": "Effects of some polyamines, polyanions and antitumor drugs on replicative DNA synthesis and unscheduled DNA synthesis in vitro. The effects of various compounds on replicative DNA synthesis in permeable mouse ascites sarcoma cells and on unscheduled DNA synthesis in permeable cells or in isolated rat liver nuclei were studied. Polyamines such as spermidine, putrescine and cadaverine inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by spermidine and cadaverine, but slightly stimulated by putrescine at low concentrations. Aurintricarboxylic acid, a low molecular weight polyanion, inhibited both replicative DNA synthesis and unscheduled DNA synthesis. Replicative DNA synthesis was inhibited by heparin, a high molecular weight polyanion, whereas unscheduled DNA synthesis was stimulated at low heparin concentrations. Antitumor drugs such as daunomycin, neocarzinostatin and bleomycin inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by daunomycin, slightly induced by neocarzinostatin and highly induced by bleomycin. The present system was thought to be useful for studying the separate effects of various drugs on either replicative DNA synthesis or unscheduled DNA synthesis in vitro."} {"id": "PMID:158944", "title": "Sequential radioimmunoassay of unconjugated and conjugated estrogen in male human plasma.", "content": "A sequential radioimmunoassay procedure for unconjugated and conjugated estrone, estradiol-17 beta and estriol in male human plasma was developed. The blank values in this assay for unconjugated estrone, estradiol-17 beta, estriol conjugated estrone, estradiol-17 beta and conjugated estriol were 0.36 +/- 1.14 pg, 3.90 +/- 2.75 pg, 2.25 +/- 2.08 pg, 0.92 +/- 1.51 pg, 5.02 +/- 2.86 pg and 3.12 +/- 2.97 pg, respectively. Mean values of unconjugated estrone, estradiol-17 beta, estriol, conjugated estrone, estradiol-17 beta and conjugated estriol in plasma from 28 normal adult males were 38.4 +/- 13.4 pg/ml, 32.6 +/- 9.90 pg/ml, 4.06 +/- 3.68 pg/ml, 34.2 +/- 13.8 pg/ml, 40.4 +/- 12.3 pg/ml and 31.8 +/- 7.41 pg/ml, respectively. Both unconjugated and conjugated estrogen levels in patients with liver cirrhosis were elevated and conjugated estrogen, especially estriol levels, in patients with renal insufficiency were markedly elevated.", "contents": "Sequential radioimmunoassay of unconjugated and conjugated estrogen in male human plasma. A sequential radioimmunoassay procedure for unconjugated and conjugated estrone, estradiol-17 beta and estriol in male human plasma was developed. The blank values in this assay for unconjugated estrone, estradiol-17 beta, estriol conjugated estrone, estradiol-17 beta and conjugated estriol were 0.36 +/- 1.14 pg, 3.90 +/- 2.75 pg, 2.25 +/- 2.08 pg, 0.92 +/- 1.51 pg, 5.02 +/- 2.86 pg and 3.12 +/- 2.97 pg, respectively. Mean values of unconjugated estrone, estradiol-17 beta, estriol, conjugated estrone, estradiol-17 beta and conjugated estriol in plasma from 28 normal adult males were 38.4 +/- 13.4 pg/ml, 32.6 +/- 9.90 pg/ml, 4.06 +/- 3.68 pg/ml, 34.2 +/- 13.8 pg/ml, 40.4 +/- 12.3 pg/ml and 31.8 +/- 7.41 pg/ml, respectively. Both unconjugated and conjugated estrogen levels in patients with liver cirrhosis were elevated and conjugated estrogen, especially estriol levels, in patients with renal insufficiency were markedly elevated."} {"id": "PMID:158945", "title": "Partial purification and biological activities and properties of chick growth factors.", "content": "Cellular stimulating factors on cell proliferation in the supernatants of chick embryo carcases and adult muscles were studied. There were plural stimulating factors in embryonic and adult muscular supernatants that promoted cell proliferation without any supplement of sera and other materials. Salting-out methods with ammonium sulfate, ethanol fractionation, and isoelectric precipitation were used to isolate the stimulating factors, and these three methods proved the presence of plural stimulants on cell proliferation in the supernatants of chick embryo and adult muscles. The stimulants had altered physico-chemical properties and biological activities due to embryological development. The embryonic stimulants enhanced the synthesis of DNA and protein remarkably, and RNA synthesis in whole cell systems slightly. The muscular stimulants enhanced protein synthesis without any stimulation of DNA and RNA synthesis. Partial purification of the stimulants from the ethanol fractions was performed by DEAE-cellulose chromatography and Sephadex gel chromatography.", "contents": "Partial purification and biological activities and properties of chick growth factors. Cellular stimulating factors on cell proliferation in the supernatants of chick embryo carcases and adult muscles were studied. There were plural stimulating factors in embryonic and adult muscular supernatants that promoted cell proliferation without any supplement of sera and other materials. Salting-out methods with ammonium sulfate, ethanol fractionation, and isoelectric precipitation were used to isolate the stimulating factors, and these three methods proved the presence of plural stimulants on cell proliferation in the supernatants of chick embryo and adult muscles. The stimulants had altered physico-chemical properties and biological activities due to embryological development. The embryonic stimulants enhanced the synthesis of DNA and protein remarkably, and RNA synthesis in whole cell systems slightly. The muscular stimulants enhanced protein synthesis without any stimulation of DNA and RNA synthesis. Partial purification of the stimulants from the ethanol fractions was performed by DEAE-cellulose chromatography and Sephadex gel chromatography."} {"id": "PMID:158946", "title": "Characteristics of pressure sensing balloons made of various polymeric materials.", "content": "A variety of polymeric materials (polyurethane, polypropylene, polyethylene and polyvinylidine copolymer) have been evaluated for suitability in making of air-filled balloon to detect intraluminal pressure. The polyurethanes, in particular ECD, proved to be most suitable because of the ease of fabrication, low permeability to air and high frequency characteristics. Polyvinylidine copolymer was adequate but suffered from difficulties in fabrication. Polypropylene and polyethylene, available in film, were troublesome in making balloon and displayed low frequency characteristics.", "contents": "Characteristics of pressure sensing balloons made of various polymeric materials. A variety of polymeric materials (polyurethane, polypropylene, polyethylene and polyvinylidine copolymer) have been evaluated for suitability in making of air-filled balloon to detect intraluminal pressure. The polyurethanes, in particular ECD, proved to be most suitable because of the ease of fabrication, low permeability to air and high frequency characteristics. Polyvinylidine copolymer was adequate but suffered from difficulties in fabrication. Polypropylene and polyethylene, available in film, were troublesome in making balloon and displayed low frequency characteristics."} {"id": "PMID:158947", "title": "Lymphocyte cytotoxicity against allogeneic cultured cells in gynecologic malignancy.", "content": "Peripheral blood lymphocytes from patients with gynecologic cancer were tested by micro-cytotoxicity assay against two types of allogeneic cultured cancer cell lines: squamous cell carcinoma and adenocarcinoma. Lymphocytes from cancer patients with squamous cell carcinoma or adenocarcinoma were equally cytotoxic against these target cells. In addition, lymphocytes from healthy controls and myoma patients were also cytotoxic for these cell lines. No significant difference in cytotoxic activities was detected among the cancer patients and controls. However, a good correlation was observed between cytotoxic activity and non-specific lymphocyte responses. It was concluded that this assay sysetm is not suitable for measuring cell-mediated immunity against tumor specific antigens but does estimate non-specific resistance against cancer.", "contents": "Lymphocyte cytotoxicity against allogeneic cultured cells in gynecologic malignancy. Peripheral blood lymphocytes from patients with gynecologic cancer were tested by micro-cytotoxicity assay against two types of allogeneic cultured cancer cell lines: squamous cell carcinoma and adenocarcinoma. Lymphocytes from cancer patients with squamous cell carcinoma or adenocarcinoma were equally cytotoxic against these target cells. In addition, lymphocytes from healthy controls and myoma patients were also cytotoxic for these cell lines. No significant difference in cytotoxic activities was detected among the cancer patients and controls. However, a good correlation was observed between cytotoxic activity and non-specific lymphocyte responses. It was concluded that this assay sysetm is not suitable for measuring cell-mediated immunity against tumor specific antigens but does estimate non-specific resistance against cancer."} {"id": "PMID:158948", "title": "Heat stable cell growth inhibiting factor isolated from rat liver microsomes.", "content": "A heat stable cell growth inhibiting factor was isolated from rat liver microsomes by hot salt extraction, ethanol fractionation and the hot phenol method. The factor was contained in the RNA fraction (designated as mhRNA). mhRNA inhibited the growth of mouse fibroblast (L-929) cells at a relatively low concentration (55 microgram/ml of culture medium). The molecular weight of mhRNA was about 27,000 and the base composition was guanine and cytosine rich.", "contents": "Heat stable cell growth inhibiting factor isolated from rat liver microsomes. A heat stable cell growth inhibiting factor was isolated from rat liver microsomes by hot salt extraction, ethanol fractionation and the hot phenol method. The factor was contained in the RNA fraction (designated as mhRNA). mhRNA inhibited the growth of mouse fibroblast (L-929) cells at a relatively low concentration (55 microgram/ml of culture medium). The molecular weight of mhRNA was about 27,000 and the base composition was guanine and cytosine rich."} {"id": "PMID:158949", "title": "Determination of the disappearance rate of azathioprine from circulating rat blood by high-pressure liquid chromatography.", "content": "A rapid and specific method of high-pressure liquid chromatography for determining 6-(1-methyl-4-nitro-5-imidazole) mercaptopurine (azathioprine) in the blood was developed using mu Bondapak C18 as adsorbent and 30% aquous methanol as eluent. Azathioprine was completely separated from related compounds in blood. The standard curve showed a linear relationship at least between 0.6 and 30 micrograms per ml of serum. Recovery was satisfactory and the analytical time needed was less than 20 min. Disappearance rates of azathioprine from circulating blood in rats were 0.026 in probenecid-treated rats, and 0.103 in intact rats.", "contents": "Determination of the disappearance rate of azathioprine from circulating rat blood by high-pressure liquid chromatography. A rapid and specific method of high-pressure liquid chromatography for determining 6-(1-methyl-4-nitro-5-imidazole) mercaptopurine (azathioprine) in the blood was developed using mu Bondapak C18 as adsorbent and 30% aquous methanol as eluent. Azathioprine was completely separated from related compounds in blood. The standard curve showed a linear relationship at least between 0.6 and 30 micrograms per ml of serum. Recovery was satisfactory and the analytical time needed was less than 20 min. Disappearance rates of azathioprine from circulating blood in rats were 0.026 in probenecid-treated rats, and 0.103 in intact rats."} {"id": "PMID:158950", "title": "Fulminant hepatic failure during remission from leukemia: three cases associated with massive liver cell necrosis and hepatitis B virus.", "content": "Three patients at various stages of remission from leukemia died following the development of massive liver necrosis within only 4-6 days. All had either hepatitis B surface antigen or antibody in their sera, and two of them experienced severe epigastric pain before the onset of liver injury. Hepatitis B surface antigen appeared in two of these patients after remission from leukemia. Serum gamma-globulin levels increased with decreasing doses of prednisolone and other antileukemic drugs, and hepatic cell necrosis occurred extensively. Localization of hepatitis B surface antigen in their livers revealed a strong positive reaction in the phagocytic cells. These observations strongly suggest that hepatitis B virus may be causally related to the fulminant hepatic failure at least in two of the reported leukemic patients.", "contents": "Fulminant hepatic failure during remission from leukemia: three cases associated with massive liver cell necrosis and hepatitis B virus. Three patients at various stages of remission from leukemia died following the development of massive liver necrosis within only 4-6 days. All had either hepatitis B surface antigen or antibody in their sera, and two of them experienced severe epigastric pain before the onset of liver injury. Hepatitis B surface antigen appeared in two of these patients after remission from leukemia. Serum gamma-globulin levels increased with decreasing doses of prednisolone and other antileukemic drugs, and hepatic cell necrosis occurred extensively. Localization of hepatitis B surface antigen in their livers revealed a strong positive reaction in the phagocytic cells. These observations strongly suggest that hepatitis B virus may be causally related to the fulminant hepatic failure at least in two of the reported leukemic patients."} {"id": "PMID:158951", "title": "Bartter's syndrome--case report.", "content": "A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.", "contents": "Bartter's syndrome--case report. A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation."} {"id": "PMID:158952", "title": "A case of ectopic renin-secreting orbital hemangiopericytoma associated with juvenile hypertension and hypokalemia.", "content": "An unusual case of orbital tumor with high renin content and severe hypertension is described. The patient was a 15-year-old girl with juvenile hypertension (200-140 mmHg) associated with right exophthalmos and hypokalemia. The patient showed extremely high levels of plasma renin activity and plasma aldosterone concentration. No difference was present in plasma renin activity from either side of the renal veins. Preoperatively, hypertension responded to treatment with spironolactone. The tumor could not be completely removed because of intracranial metastasis and infiltration, and the hyperreninemia and secondary hyperaldosteronism persisted. The renin content in the orbital tissue was 1,403-2,225 ng/angiotensin I generated/h/g wet weight of tissue. The postmortem histopathologic diagnosis was orbital hemangiopericytoma. This is the first case of extrarenal (ectopic) renin-secreting (or -producing) hemangiopericytoma of the orbital origin. Furthermore this case is worthy of note in the point of view of the presence of the extrarenal renin-angiotensin system, particularly in the brain.", "contents": "A case of ectopic renin-secreting orbital hemangiopericytoma associated with juvenile hypertension and hypokalemia. An unusual case of orbital tumor with high renin content and severe hypertension is described. The patient was a 15-year-old girl with juvenile hypertension (200-140 mmHg) associated with right exophthalmos and hypokalemia. The patient showed extremely high levels of plasma renin activity and plasma aldosterone concentration. No difference was present in plasma renin activity from either side of the renal veins. Preoperatively, hypertension responded to treatment with spironolactone. The tumor could not be completely removed because of intracranial metastasis and infiltration, and the hyperreninemia and secondary hyperaldosteronism persisted. The renin content in the orbital tissue was 1,403-2,225 ng/angiotensin I generated/h/g wet weight of tissue. The postmortem histopathologic diagnosis was orbital hemangiopericytoma. This is the first case of extrarenal (ectopic) renin-secreting (or -producing) hemangiopericytoma of the orbital origin. Furthermore this case is worthy of note in the point of view of the presence of the extrarenal renin-angiotensin system, particularly in the brain."} {"id": "PMID:158953", "title": "Q waves and coronary artery disease.", "content": "In a consecutive series of 234 patients admitted for selective coronary arteriography, 78 had pathological Q waves. In 32 of these 78 patients, ECG showed left ventricular hypertrophy, QRS duration of greater than or equal to 0.12 sec, incomplete left bundle branch block, or left axis deviation. Fourteen (44%) of these 32 patients had coronary artery disease (CAD), while 40 (87%) of the remaining 46 patients without these ECG changes had CAD (p less than 0.0005). Among the 46 patients, 34 of 35 with angina pectoris had CAD compared to 6 of 11 without angina pectoris (p less than 0.01). Our study thus shows that Q waves may be reliable predictors of CAD especially in patients with angina pectoris.", "contents": "Q waves and coronary artery disease. In a consecutive series of 234 patients admitted for selective coronary arteriography, 78 had pathological Q waves. In 32 of these 78 patients, ECG showed left ventricular hypertrophy, QRS duration of greater than or equal to 0.12 sec, incomplete left bundle branch block, or left axis deviation. Fourteen (44%) of these 32 patients had coronary artery disease (CAD), while 40 (87%) of the remaining 46 patients without these ECG changes had CAD (p less than 0.0005). Among the 46 patients, 34 of 35 with angina pectoris had CAD compared to 6 of 11 without angina pectoris (p less than 0.01). Our study thus shows that Q waves may be reliable predictors of CAD especially in patients with angina pectoris."} {"id": "PMID:158956", "title": "Dynamics of kallikreinogen under hemodialysis.", "content": "There are many complications due to hemodialysis, causes of which seem to lie under disorders of the coagulation system, fibrinolytic system, and kinin system. Therefore, it is important to understand the dynamics of these systems during hemodialysis. Accordingly, kallikreinogen, plasminogen, plasmin inhibitors, contact factor, antithrombin, and prothrombin were assayed during the experimental dialysis, experimental ultrafiltration and clinical hemodialysis. Plasmin inhibitors decreased remarkably by dialysis. They then recovered the pre-dialytic values as time went on. Kallikreinogen did not show any definite tendency immediately after the beginning of dialysis, but two hours later its value rather increased relative to thepre-dialytic value. It was supposed that this increase was caused by reactive hyperproduction due to gradual consumption of kallikreinogen. Contact factor slightly decreased by dialysis, whereas prothrombin and antithrombin decreased apparently. When hemodialysis is practiced, it is necessary to fully realize that the coagulation system, fibrinolytic system, and kinin system might lose their balance.", "contents": "Dynamics of kallikreinogen under hemodialysis. There are many complications due to hemodialysis, causes of which seem to lie under disorders of the coagulation system, fibrinolytic system, and kinin system. Therefore, it is important to understand the dynamics of these systems during hemodialysis. Accordingly, kallikreinogen, plasminogen, plasmin inhibitors, contact factor, antithrombin, and prothrombin were assayed during the experimental dialysis, experimental ultrafiltration and clinical hemodialysis. Plasmin inhibitors decreased remarkably by dialysis. They then recovered the pre-dialytic values as time went on. Kallikreinogen did not show any definite tendency immediately after the beginning of dialysis, but two hours later its value rather increased relative to thepre-dialytic value. It was supposed that this increase was caused by reactive hyperproduction due to gradual consumption of kallikreinogen. Contact factor slightly decreased by dialysis, whereas prothrombin and antithrombin decreased apparently. When hemodialysis is practiced, it is necessary to fully realize that the coagulation system, fibrinolytic system, and kinin system might lose their balance."} {"id": "PMID:158959", "title": "Ultrasound of arterial graft surgery complications.", "content": "The value of gray scale ultrasound in evaluating primary diseases of the abdominal aorta and peripheral vessels has been well documented. However, only limited attention has been given to complications associated with arterial graft surgery. Twelve patients with a variety of complications are reported. These include 10 anastomotic pseudoaneurysms, one abscess, two \"aneurysms\" in degenerated graft material, and four serous fluid collections around intact Dacron grafts. The latter two complications are previously unreported.", "contents": "Ultrasound of arterial graft surgery complications. The value of gray scale ultrasound in evaluating primary diseases of the abdominal aorta and peripheral vessels has been well documented. However, only limited attention has been given to complications associated with arterial graft surgery. Twelve patients with a variety of complications are reported. These include 10 anastomotic pseudoaneurysms, one abscess, two \"aneurysms\" in degenerated graft material, and four serous fluid collections around intact Dacron grafts. The latter two complications are previously unreported."} {"id": "PMID:158960", "title": "Cardiovascular malformations in the fetal alcohol syndrome.", "content": "Cardiovascular anomalies are a frequently reported feature of the fetal alcohol syndrome, but only rarely have such children been catheterized. This article fully described the cardiac anomaly in two infants with this syndrome. The malformations found in both cases include a ventricular septal defect, and the rather unusual finding of pulmonary artery dysplasia.", "contents": "Cardiovascular malformations in the fetal alcohol syndrome. Cardiovascular anomalies are a frequently reported feature of the fetal alcohol syndrome, but only rarely have such children been catheterized. This article fully described the cardiac anomaly in two infants with this syndrome. The malformations found in both cases include a ventricular septal defect, and the rather unusual finding of pulmonary artery dysplasia."} {"id": "PMID:158962", "title": "Effects of cardiac hypertrophy secondary to hypertension on the coronary circulation.", "content": "For many years clinicians have suspected that hypertrophied ventricles have an inadequate coronary circulation. Recent studies have confirmed early observations that flow per gram in hypertrophied ventricles is normal at rest. However, coronary vascular resistance is greatly increased when hypertension is the cause of left ventricular hypertrophy. Studies that have employed labeled microspheres to assess regional myocardial perfusion have shown that the transmural distribution of myocardial perfusion is often abnormal in dogs with left ventricular hypertrophy. In addition, studies of cardiac hypertrophy in many animal models have shown that maximal coronary vasodilatation is limited substantially. Furthermore, when hypertrophied hearts are subjected to a physiologic stress that induces coronary vasodilatation, endocardial underperfusion occurs frequently. Thus, studies in animals suggest that cardiac hypertrophy adversely affects the coronary circulation. The availability of new techniques for estimating phasic and transmural coronary blood flow in man should make it possible to extend these studies to patients with cardiac hypertrophy.", "contents": "Effects of cardiac hypertrophy secondary to hypertension on the coronary circulation. For many years clinicians have suspected that hypertrophied ventricles have an inadequate coronary circulation. Recent studies have confirmed early observations that flow per gram in hypertrophied ventricles is normal at rest. However, coronary vascular resistance is greatly increased when hypertension is the cause of left ventricular hypertrophy. Studies that have employed labeled microspheres to assess regional myocardial perfusion have shown that the transmural distribution of myocardial perfusion is often abnormal in dogs with left ventricular hypertrophy. In addition, studies of cardiac hypertrophy in many animal models have shown that maximal coronary vasodilatation is limited substantially. Furthermore, when hypertrophied hearts are subjected to a physiologic stress that induces coronary vasodilatation, endocardial underperfusion occurs frequently. Thus, studies in animals suggest that cardiac hypertrophy adversely affects the coronary circulation. The availability of new techniques for estimating phasic and transmural coronary blood flow in man should make it possible to extend these studies to patients with cardiac hypertrophy."} {"id": "PMID:158966", "title": "Echocardiographic dimensions in borderline and sustained hypertension.", "content": "Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.", "contents": "Echocardiographic dimensions in borderline and sustained hypertension. Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system."} {"id": "PMID:158968", "title": "Cardiac hypertrophy: its characteristics as a growth process.", "content": "The causal relation between cardiac function and growth is analyzed in this review article. Three different levels of development are discussed: cytodifferentiation, embryogenesis and postnatal development. The earliest stage of cardiac morphogenesis, that is, the appearance of cell-specific proteins and of spontaneous contractions, appears to be independent of hemodynamic forces. Also, the first major morphologic transformation of the primitive heart, looping, is the intrinsic property of the heart itself. However, at any later stage of life, hemodynamic function in both health and disease is closely coupled to cardiac growth.", "contents": "Cardiac hypertrophy: its characteristics as a growth process. The causal relation between cardiac function and growth is analyzed in this review article. Three different levels of development are discussed: cytodifferentiation, embryogenesis and postnatal development. The earliest stage of cardiac morphogenesis, that is, the appearance of cell-specific proteins and of spontaneous contractions, appears to be independent of hemodynamic forces. Also, the first major morphologic transformation of the primitive heart, looping, is the intrinsic property of the heart itself. However, at any later stage of life, hemodynamic function in both health and disease is closely coupled to cardiac growth."} {"id": "PMID:158971", "title": "Is arterial pressure the sole factor responsible for hypertensive cardiac hypertrophy?", "content": "Increased arterial pressure is obviously the major stimulus to cardiac hypertrophy in hypertension. However, different studies suggest that in addition to the pressure load, other factors could play participating roles in determining the degree of ventricular hypertrophy in response to the hypertensive disease as well as the degree of its reversal after control of arterial pressure. These other mechanisms include genetic factors and concimitant processes such as aging and the presence of cardiomyopathy or other disease. Two neurohumoral influences, namely, the adrenergic and the renin-angiotensin systems, may also participate, and the early evidence supporting these possible contributing factors is cited. Further studies are needed to determine the relative importance of each of these factors in different types of hypertension and in their response to different modes of antihypertensive therapy.", "contents": "Is arterial pressure the sole factor responsible for hypertensive cardiac hypertrophy? Increased arterial pressure is obviously the major stimulus to cardiac hypertrophy in hypertension. However, different studies suggest that in addition to the pressure load, other factors could play participating roles in determining the degree of ventricular hypertrophy in response to the hypertensive disease as well as the degree of its reversal after control of arterial pressure. These other mechanisms include genetic factors and concimitant processes such as aging and the presence of cardiomyopathy or other disease. Two neurohumoral influences, namely, the adrenergic and the renin-angiotensin systems, may also participate, and the early evidence supporting these possible contributing factors is cited. Further studies are needed to determine the relative importance of each of these factors in different types of hypertension and in their response to different modes of antihypertensive therapy."} {"id": "PMID:158976", "title": "Idiopathic hypertrophic subaortic stenosis: evaluation of anginal symptoms with thallium-201 myocardial imaging.", "content": "The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis.", "contents": "Idiopathic hypertrophic subaortic stenosis: evaluation of anginal symptoms with thallium-201 myocardial imaging. The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis."} {"id": "PMID:158979", "title": "Neoplasms of immunoregulatory cells.", "content": "This paper provides an overview of neoplasms which appear to be derived from immunoregulatory cells. Normal T cells play a critical role in the regulation of humoral immune responses by acting as potentiators (helper cells) or inhibitors (suppressor cells) of the B cell transition into immunoglobulin-secreting plasma cells. Certain patients with leukemias or lymphomas of T-cell origin may provide a resource for obtaining homogeneous populations of cells which act as either helper cells (e.g., some patients with the S\u00e9zary syndrome) or suppressor cells (e.g., some patients with acute or subacute T-leukemia). The clinical and theoretic implications of such immunoregulatory cell neoplasms are discussed.", "contents": "Neoplasms of immunoregulatory cells. This paper provides an overview of neoplasms which appear to be derived from immunoregulatory cells. Normal T cells play a critical role in the regulation of humoral immune responses by acting as potentiators (helper cells) or inhibitors (suppressor cells) of the B cell transition into immunoglobulin-secreting plasma cells. Certain patients with leukemias or lymphomas of T-cell origin may provide a resource for obtaining homogeneous populations of cells which act as either helper cells (e.g., some patients with the S\u00e9zary syndrome) or suppressor cells (e.g., some patients with acute or subacute T-leukemia). The clinical and theoretic implications of such immunoregulatory cell neoplasms are discussed."} {"id": "PMID:158980", "title": "Comparison of DRO and DRI on rate of suppression of self-injurious behavior.", "content": "Two procedures were used to compare the effects of differential reinforcement of other behavior (DRO) and differential reinforcement of incompatible behavior (DRI) on self-injurious behavior (SIB) of three profoundly retarded head-bangers in a multiple-schedule within-subjects design. We found that rewarding a response specifically incompatible with SIB suppressed it more rapidly than applying DRO without specifying an alternative response. The relationship of collateral behaviors to SIB were dependent upon the repertoires of the individual clients.", "contents": "Comparison of DRO and DRI on rate of suppression of self-injurious behavior. Two procedures were used to compare the effects of differential reinforcement of other behavior (DRO) and differential reinforcement of incompatible behavior (DRI) on self-injurious behavior (SIB) of three profoundly retarded head-bangers in a multiple-schedule within-subjects design. We found that rewarding a response specifically incompatible with SIB suppressed it more rapidly than applying DRO without specifying an alternative response. The relationship of collateral behaviors to SIB were dependent upon the repertoires of the individual clients."} {"id": "PMID:158981", "title": "Isolation and characterization of myosin in the human term placenta.", "content": "The major contractile protein myosin was isolated and characterized from the smooth muscle of human term placentas. Placental myosin originates chiefly in the anchoring villi which bridge the fetal and maternal surfaces of the placenta. The molecular weight of placental myosin is about 460,000; it is composed of two heavy chains of 200,000 molecular weight and two pairs of light chains with 13,500 and 17,500 molecular weights. The adenosine triphosphatase (ATPase) of the myosin is activated by potassium and calcium and it is inhibited by magnesium. Placental actomyosin ATPase is activated by magensium. Contraction and relaxation of the smooth muscle in the anchoring villi are thought to adjust the volume of the intervillous space; thus, actin-myosin interaction is implicated in the regulation of placental hemodynamics.", "contents": "Isolation and characterization of myosin in the human term placenta. The major contractile protein myosin was isolated and characterized from the smooth muscle of human term placentas. Placental myosin originates chiefly in the anchoring villi which bridge the fetal and maternal surfaces of the placenta. The molecular weight of placental myosin is about 460,000; it is composed of two heavy chains of 200,000 molecular weight and two pairs of light chains with 13,500 and 17,500 molecular weights. The adenosine triphosphatase (ATPase) of the myosin is activated by potassium and calcium and it is inhibited by magnesium. Placental actomyosin ATPase is activated by magensium. Contraction and relaxation of the smooth muscle in the anchoring villi are thought to adjust the volume of the intervillous space; thus, actin-myosin interaction is implicated in the regulation of placental hemodynamics."} {"id": "PMID:158982", "title": "Immune complex injury of the lung.", "content": "Abundant evidence currently exists to suggest that immune complexes play an important role in inflammatory diseases of the lung. Clinically, idiopathic pulmonary fibrosis, eosinophilic granuloma of lung, and systemic lupus erythematosus have been shown to be associated with the presence of immune complexes both in lung and in the serum. Experimentally, there is compelling evidence that acute lung injury can be triggered by the deposition of complexes in vascular walls or by the presence of performed immune complexes instilled into the airways. The observed reactions are, as expected, complement- and neutrophil-dependent. The morphologic changes in lung caused by products of complement activation (C5a and related peptides) depend on whether complement activation occurs within the vasculature or within the airways. Airway activation is associated with intraalveolar accumulations of neutrophils, while intravascular activation leads to intracapillary sequestration of neutrophils. The chronic formation of immune complexes within the vasculature (in the model of \"chronic serum sickness\") leads to an interstitial fibrotic reaction and a thickening of basement membranes. Recent studies of intravascularly infused preformed immune complexes indicate a proclivity for certain types of complexes to localize within lung. These \"lung-seeking\" complexes differ from non-lung-seeking complexes only in the ratio of antigen to antibody. Complement does not seem to alter the tendancy for certain complexes to localize within lung. These studies emphasize the potential importance of immune complexes in lung injury and point out the variety of mechanisms involved in both the localization process and the injury process.", "contents": "Immune complex injury of the lung. Abundant evidence currently exists to suggest that immune complexes play an important role in inflammatory diseases of the lung. Clinically, idiopathic pulmonary fibrosis, eosinophilic granuloma of lung, and systemic lupus erythematosus have been shown to be associated with the presence of immune complexes both in lung and in the serum. Experimentally, there is compelling evidence that acute lung injury can be triggered by the deposition of complexes in vascular walls or by the presence of performed immune complexes instilled into the airways. The observed reactions are, as expected, complement- and neutrophil-dependent. The morphologic changes in lung caused by products of complement activation (C5a and related peptides) depend on whether complement activation occurs within the vasculature or within the airways. Airway activation is associated with intraalveolar accumulations of neutrophils, while intravascular activation leads to intracapillary sequestration of neutrophils. The chronic formation of immune complexes within the vasculature (in the model of \"chronic serum sickness\") leads to an interstitial fibrotic reaction and a thickening of basement membranes. Recent studies of intravascularly infused preformed immune complexes indicate a proclivity for certain types of complexes to localize within lung. These \"lung-seeking\" complexes differ from non-lung-seeking complexes only in the ratio of antigen to antibody. Complement does not seem to alter the tendancy for certain complexes to localize within lung. These studies emphasize the potential importance of immune complexes in lung injury and point out the variety of mechanisms involved in both the localization process and the injury process."} {"id": "PMID:158983", "title": "Myofibrillar ATPase activity in rat heart after chronic propranolol administration.", "content": "A previous study has shown that chronic chemical sympathectomy brought about by 6-hydroxydopamine injections results in a dpression in myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. To determine whether chronic beta-adrenergic receptor blockade elicits similar alterations in cardiac contractile-protein ATPase activity, adult rats were given twice-daily injections of propranolol 7 days/wk for 2 wk. Effective beta-adrenergic receptor blockade was verified by the lack of hemodynamic responsiveness to isoproterenol infusion. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar ATPase activity was 295 +/- 8 nmol Pi.mg-1.min-1 in controls. Enzyme activity was not significantly different in propranolol-injected rats. The results demonstrate that chronic propranolol administration does not alter the ATPase activity of cardiac myofibrils. Therefore, it seems likely that the altered contractile-protein enzymatic properties resulting from chronic chemical sympathectomy do not occur as the result of a reducted level of cardiac beta-adrenergic receptor stimulation.", "contents": "Myofibrillar ATPase activity in rat heart after chronic propranolol administration. A previous study has shown that chronic chemical sympathectomy brought about by 6-hydroxydopamine injections results in a dpression in myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. To determine whether chronic beta-adrenergic receptor blockade elicits similar alterations in cardiac contractile-protein ATPase activity, adult rats were given twice-daily injections of propranolol 7 days/wk for 2 wk. Effective beta-adrenergic receptor blockade was verified by the lack of hemodynamic responsiveness to isoproterenol infusion. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar ATPase activity was 295 +/- 8 nmol Pi.mg-1.min-1 in controls. Enzyme activity was not significantly different in propranolol-injected rats. The results demonstrate that chronic propranolol administration does not alter the ATPase activity of cardiac myofibrils. Therefore, it seems likely that the altered contractile-protein enzymatic properties resulting from chronic chemical sympathectomy do not occur as the result of a reducted level of cardiac beta-adrenergic receptor stimulation."} {"id": "PMID:158984", "title": "Temperature- and Mg-ATP-dependent regulation of Ca2+ sensitivity of smooth muscle actomyosin ATPase.", "content": "Many smooth muscles on metabolic depletion undergo a contraction that is insensitive to EGTA [ethylene glycol-bis (beta-aminoethylether)N,N-tetraacetic acid]. Chicken gizzard actomyosin shows a progressive loss of Ca sensitivity accompanied by activation of EGTA-Mg-ATPase at temperatures near 37 degrees C with decreasing ATP concentrations. Ca2+-dependent phosphorylation still occurs under these conditions when the ATPase is Ca insensitive. Activation of EGTA-Mg-ATPase at low ATP concentration is not due to a pseudo-ATPase, or due to denautration of the actomyosin at 37 degrees C. Magnesium concentrations above 1 mM are required for observing the enhanced EGTA-Mg-ATPase activity and the Ca sensitivity is very markedly influenced by the magnesium concentrations of medium at low ATP. When the Mg-to-ATP ratio (5:1) was kept constant for varying ATP concentrations, activation of EGTA-ATPase was not observed. This activation was not due to the characteristics of the ATP regenerating system (phosphoenolpyruvate and pyruvate kinase) because with phosphocreatine and creatine phosphokinase similar results were obtained. Thus the EGTA-insensitive rise in tension during metabolic depletion is due to activation of Mg-ATPase and loss of Ca sensitivity at 37 degrees C, a temperature at which mammalian smooth muscles normally function.", "contents": "Temperature- and Mg-ATP-dependent regulation of Ca2+ sensitivity of smooth muscle actomyosin ATPase. Many smooth muscles on metabolic depletion undergo a contraction that is insensitive to EGTA [ethylene glycol-bis (beta-aminoethylether)N,N-tetraacetic acid]. Chicken gizzard actomyosin shows a progressive loss of Ca sensitivity accompanied by activation of EGTA-Mg-ATPase at temperatures near 37 degrees C with decreasing ATP concentrations. Ca2+-dependent phosphorylation still occurs under these conditions when the ATPase is Ca insensitive. Activation of EGTA-Mg-ATPase at low ATP concentration is not due to a pseudo-ATPase, or due to denautration of the actomyosin at 37 degrees C. Magnesium concentrations above 1 mM are required for observing the enhanced EGTA-Mg-ATPase activity and the Ca sensitivity is very markedly influenced by the magnesium concentrations of medium at low ATP. When the Mg-to-ATP ratio (5:1) was kept constant for varying ATP concentrations, activation of EGTA-ATPase was not observed. This activation was not due to the characteristics of the ATP regenerating system (phosphoenolpyruvate and pyruvate kinase) because with phosphocreatine and creatine phosphokinase similar results were obtained. Thus the EGTA-insensitive rise in tension during metabolic depletion is due to activation of Mg-ATPase and loss of Ca sensitivity at 37 degrees C, a temperature at which mammalian smooth muscles normally function."} {"id": "PMID:158985", "title": "Changes in the sensitivity of left atrial receptors following reversal of heart failure.", "content": "Recordings were made from left atrial type B receptors in six mongrel dogs after recovery from the cardiac effects of a chronic AV fistula. All animals showed hemodynamic and clinical signs of congestive heart failure after 44.5 +/- 3.6 days with a patent Dacron shunt between the aorta and inferior vena cava below the level of the renal arteries. The stimulus-response curves of the left atrial stretch receptors (change in spikes/cardiac cycle or in spikes/minute vs. change in left atrial pressure) after 45.2 +/- 7.2 days of shunt closure were similar to those seen in sham-operated dogs from a previous study. However, the slope of the stimulus-response curve of the dogs in which the AV fistula was closed was significantly greater than the slope of the curve from the AV fistula dogs with heart failure. Radiographs indicated that after shunt closure, cardiac dilatation had regressed. This study incidates that a decrease in the sensitivity of left atrial receptors in dogs with congestive heart failure is a reversible phenomenon and that the initial depression is most likely related to the concomitant cardiac dilatation that accompanies the failure state.", "contents": "Changes in the sensitivity of left atrial receptors following reversal of heart failure. Recordings were made from left atrial type B receptors in six mongrel dogs after recovery from the cardiac effects of a chronic AV fistula. All animals showed hemodynamic and clinical signs of congestive heart failure after 44.5 +/- 3.6 days with a patent Dacron shunt between the aorta and inferior vena cava below the level of the renal arteries. The stimulus-response curves of the left atrial stretch receptors (change in spikes/cardiac cycle or in spikes/minute vs. change in left atrial pressure) after 45.2 +/- 7.2 days of shunt closure were similar to those seen in sham-operated dogs from a previous study. However, the slope of the stimulus-response curve of the dogs in which the AV fistula was closed was significantly greater than the slope of the curve from the AV fistula dogs with heart failure. Radiographs indicated that after shunt closure, cardiac dilatation had regressed. This study incidates that a decrease in the sensitivity of left atrial receptors in dogs with congestive heart failure is a reversible phenomenon and that the initial depression is most likely related to the concomitant cardiac dilatation that accompanies the failure state."} {"id": "PMID:158986", "title": "Sports for the physically disabled. The 1976 Olympiad (Toronto).", "content": "The 1976 Olympiad for the Physically Disabled was the first olympiad with full competition for blind, paralyzed, and amputee athletes. More than 1,500 from 38 countries took part in wheelchair (12 events), blind (8 events), and amputee (11 events) games. Participants were classified by an international team of doctors. The athletes were accomodated in university residences with small infirmaries. A school near the games site was used as a field hospital. Rest areas were also set up. Volunteers served on the medical staff (three doctors, three nurses, three receptionists, and three physical therapists on each of two shifts per day). In addition doctors, nurses, trainers, and physical therapists rotated around various venues at the games site. Physicians treated 285 patients (184 were athletes; others were spectators) for a variety of problems, physical therapists treated 119 athletes, and trainers treated 114 athletes. Contigency plans in case of mass disaster were made but were not needed. Disabled athletes are slightly more vulnerable to stress and fatigue than able-bodied athletes. The Toronto games will probably be remembered as the turning point in the emergence of sports for the disabled from a purely rehabilitation measure to a true sporting event in its own right.", "contents": "Sports for the physically disabled. The 1976 Olympiad (Toronto). The 1976 Olympiad for the Physically Disabled was the first olympiad with full competition for blind, paralyzed, and amputee athletes. More than 1,500 from 38 countries took part in wheelchair (12 events), blind (8 events), and amputee (11 events) games. Participants were classified by an international team of doctors. The athletes were accomodated in university residences with small infirmaries. A school near the games site was used as a field hospital. Rest areas were also set up. Volunteers served on the medical staff (three doctors, three nurses, three receptionists, and three physical therapists on each of two shifts per day). In addition doctors, nurses, trainers, and physical therapists rotated around various venues at the games site. Physicians treated 285 patients (184 were athletes; others were spectators) for a variety of problems, physical therapists treated 119 athletes, and trainers treated 114 athletes. Contigency plans in case of mass disaster were made but were not needed. Disabled athletes are slightly more vulnerable to stress and fatigue than able-bodied athletes. The Toronto games will probably be remembered as the turning point in the emergence of sports for the disabled from a purely rehabilitation measure to a true sporting event in its own right."} {"id": "PMID:159008", "title": "[Intratissular immune complexes in experimental pathology (author's transl)].", "content": "Immune complexes are responsible for tissue lesions in human pathology and in experimental pathology. In this review are considered the various models in which immune complexes may be responsible for tissue lesions in experimental pathology. The methods of study are first considered. Four essential models are then described. Knowledge of these models is probably very important for better understanding of human diseases. Finally are considered the circumstances favouring the formation of immune complexes in a tissue, the affected organs and the possible pathogenic effects of these immune complexes.", "contents": "[Intratissular immune complexes in experimental pathology (author's transl)]. Immune complexes are responsible for tissue lesions in human pathology and in experimental pathology. In this review are considered the various models in which immune complexes may be responsible for tissue lesions in experimental pathology. The methods of study are first considered. Four essential models are then described. Knowledge of these models is probably very important for better understanding of human diseases. Finally are considered the circumstances favouring the formation of immune complexes in a tissue, the affected organs and the possible pathogenic effects of these immune complexes."} {"id": "PMID:159009", "title": "Occupational diseases.", "content": "This paper does not deal with occupational diseases in the narrow legal sense of the word but as part of all public health risks. Occupational health risks of the modern large-scale animal production on intensive farms differ radically from those of the traditional mixed small production farms. The main groups of occupational diseases in intensive large-scale animal production are: 1) Zoonoses. Their occurrence obviously depends on the epizootological situation. They are divided into the following groups: classic zoonoses, zoonoses with complicated ecologic relations, zoonoses associated with soil, zoonoses with natural foci or with reservoirs outside farms. 2) Lung diseases: chronic bronchitis, farmers' and brewers' lung precancerous conditions. 3) Skin diseases and allergies: dermatites, eczema and allergies. 4) Affections due to physical and mental stress: changes in the locomotor system and CNS, contribution to the development of \"civilization diseases\". 5) Accidents, poisoning, noise and vibration effects.", "contents": "Occupational diseases. This paper does not deal with occupational diseases in the narrow legal sense of the word but as part of all public health risks. Occupational health risks of the modern large-scale animal production on intensive farms differ radically from those of the traditional mixed small production farms. The main groups of occupational diseases in intensive large-scale animal production are: 1) Zoonoses. Their occurrence obviously depends on the epizootological situation. They are divided into the following groups: classic zoonoses, zoonoses with complicated ecologic relations, zoonoses associated with soil, zoonoses with natural foci or with reservoirs outside farms. 2) Lung diseases: chronic bronchitis, farmers' and brewers' lung precancerous conditions. 3) Skin diseases and allergies: dermatites, eczema and allergies. 4) Affections due to physical and mental stress: changes in the locomotor system and CNS, contribution to the development of \"civilization diseases\". 5) Accidents, poisoning, noise and vibration effects."} {"id": "PMID:159010", "title": "The role of serotonergic mechanisms on amphetamine-induced stereotyped behaviour.", "content": "The effects of 5-hydroxytryptophan (5-HTP) and p-chlorophenylalanine (PCPA) on amphetamine-induced stereotyped behaviour (ASB) and on the behavioural and EEG effects of caudate nucleus stimulation have been studied in the cat. After a pretreatment with 5-HTP (10--30 mg/kg) the threshold dose of amphetamine to induce ASB remained the same, but its pattern assumed a more organized character with reduced amplitude of stereotyped movements. On the contrary, after PCPA (200 mg/kg) a disorganized pattern of ASB was observed. 5-HTP increased and PCPA decreased the threshold of the arrest reaction induced by low frequency stimulation of ventro-lateral parts of the head of caudate nucleus. 5-HTP and PCPA also influenced in the opposite direction caudate-induced spindle waves in the neocortex. The effects of amphetamine on behavioural and EEG pattern of arrest reaction due to stimulation of the caudate nucleus were antagonized by 5-HTP and potentiated by PCPA. It is supposed that serotonergic mechanisms present in the ventro-lateral regions of the caudate nucleus can modulate stereotyped behaviour triggered by amphetamine.", "contents": "The role of serotonergic mechanisms on amphetamine-induced stereotyped behaviour. The effects of 5-hydroxytryptophan (5-HTP) and p-chlorophenylalanine (PCPA) on amphetamine-induced stereotyped behaviour (ASB) and on the behavioural and EEG effects of caudate nucleus stimulation have been studied in the cat. After a pretreatment with 5-HTP (10--30 mg/kg) the threshold dose of amphetamine to induce ASB remained the same, but its pattern assumed a more organized character with reduced amplitude of stereotyped movements. On the contrary, after PCPA (200 mg/kg) a disorganized pattern of ASB was observed. 5-HTP increased and PCPA decreased the threshold of the arrest reaction induced by low frequency stimulation of ventro-lateral parts of the head of caudate nucleus. 5-HTP and PCPA also influenced in the opposite direction caudate-induced spindle waves in the neocortex. The effects of amphetamine on behavioural and EEG pattern of arrest reaction due to stimulation of the caudate nucleus were antagonized by 5-HTP and potentiated by PCPA. It is supposed that serotonergic mechanisms present in the ventro-lateral regions of the caudate nucleus can modulate stereotyped behaviour triggered by amphetamine."} {"id": "PMID:159011", "title": "Bovine plasma cold-insoluble globulin: gross structure and function.", "content": "Bovine plasma CIg, like human CIg, is a glycoprotein with a molecular weight of approximately 450,000 daltons and consists of two homologous subunits, the alpha and beta chains. These subunits are covalently linked through disulfide bridges in their carboxyl terminal domains. The carboxyl terminal regions are presumed to contain the fibrin-reactive transamidation site. The covalent incorporation of CIg into fibrin has been conclusively demonstrated by isolation of the S-carboxymethyl derivative of the CIg-fibrin-alpha chain complex and by determination of its terminal amino acid sequences. Cold-insoluble globulin has been shown to exert a stimulatory effect on the urokinase-mediated activation of bovine plasminogen to plasmin.", "contents": "Bovine plasma cold-insoluble globulin: gross structure and function. Bovine plasma CIg, like human CIg, is a glycoprotein with a molecular weight of approximately 450,000 daltons and consists of two homologous subunits, the alpha and beta chains. These subunits are covalently linked through disulfide bridges in their carboxyl terminal domains. The carboxyl terminal regions are presumed to contain the fibrin-reactive transamidation site. The covalent incorporation of CIg into fibrin has been conclusively demonstrated by isolation of the S-carboxymethyl derivative of the CIg-fibrin-alpha chain complex and by determination of its terminal amino acid sequences. Cold-insoluble globulin has been shown to exert a stimulatory effect on the urokinase-mediated activation of bovine plasminogen to plasmin."} {"id": "PMID:159012", "title": "[Inflammatory variable epidermal naevus (atypical I.L.V.E.N.? A new entity?) (author's transl)].", "content": "The authors report a case of two sisters, having one of them left hemiatrophy, with congenital verrucose lesions, in plaques and lineary, bilateral, in extremities, presenting bouts of inflammatory extensive evolution (mostly on the atrophic side), with spontaneous resolution. Histologically the lesions match with those of Nevil's. The authors discuss the nosologic data with that of Nevil's, with epidermic nevus of Solomon and with variable erythrokeratodermis.", "contents": "[Inflammatory variable epidermal naevus (atypical I.L.V.E.N.? A new entity?) (author's transl)]. The authors report a case of two sisters, having one of them left hemiatrophy, with congenital verrucose lesions, in plaques and lineary, bilateral, in extremities, presenting bouts of inflammatory extensive evolution (mostly on the atrophic side), with spontaneous resolution. Histologically the lesions match with those of Nevil's. The authors discuss the nosologic data with that of Nevil's, with epidermic nevus of Solomon and with variable erythrokeratodermis."} {"id": "PMID:159013", "title": "[Acne-like eruption induced by pseudo-xanthoma elasticum (author's transl)].", "content": "Pseudoxanthoma elasticum can induce acne-like eruption. The lesions are located on the latero-cervical parts and consist of comedones, cysts and inflammatory nodules. Histologically, there are no transepithelial eliminations or follicultitis, but a very important granulomatosus tissue with epithelioid cells and a giganto-cellular reaction with elastotic fibres phagocytosis. These findings are different from the cases with association of P.X.E. and elastosis perforans, but they are closely related to it. We think that these features are of a very great interest for the dermatological practice.", "contents": "[Acne-like eruption induced by pseudo-xanthoma elasticum (author's transl)]. Pseudoxanthoma elasticum can induce acne-like eruption. The lesions are located on the latero-cervical parts and consist of comedones, cysts and inflammatory nodules. Histologically, there are no transepithelial eliminations or follicultitis, but a very important granulomatosus tissue with epithelioid cells and a giganto-cellular reaction with elastotic fibres phagocytosis. These findings are different from the cases with association of P.X.E. and elastosis perforans, but they are closely related to it. We think that these features are of a very great interest for the dermatological practice."} {"id": "PMID:159014", "title": "Pearson and the patient.", "content": "This lecture covers some subjects of direct concern to the medical profession contained within the Pearson Report. Each injury group was examined by the Royal Commission, both here and abroad, particular attention being paid to the relationship between tort and social security. By consensus it was proposed that in the majority of fields no-fault compensations should be extended but that the tort system should continue to have a role. Recommendations were also put forward that no damages should be permitted for non-pecuniary loss during the first 3 months and that the full value of the social security benefits should be deductible from all tort damages. Damages for permanent injury or death should be index-linked periodic payments. A new no-fault compensation scheme for road accidents was described as well as a new disabled children's allowance of 4 pounds per week with a mobility allowance at the lower age of 2 years. Medical injury was examined carefully, but it was decided that negligence liability should continue unchanged, with the proviso that the no-fault compensation schemes in New Zealand and in Sweden should be followed. These two schemes have therefore been described in some detail.", "contents": "Pearson and the patient. This lecture covers some subjects of direct concern to the medical profession contained within the Pearson Report. Each injury group was examined by the Royal Commission, both here and abroad, particular attention being paid to the relationship between tort and social security. By consensus it was proposed that in the majority of fields no-fault compensations should be extended but that the tort system should continue to have a role. Recommendations were also put forward that no damages should be permitted for non-pecuniary loss during the first 3 months and that the full value of the social security benefits should be deductible from all tort damages. Damages for permanent injury or death should be index-linked periodic payments. A new no-fault compensation scheme for road accidents was described as well as a new disabled children's allowance of 4 pounds per week with a mobility allowance at the lower age of 2 years. Medical injury was examined carefully, but it was decided that negligence liability should continue unchanged, with the proviso that the no-fault compensation schemes in New Zealand and in Sweden should be followed. These two schemes have therefore been described in some detail."} {"id": "PMID:159018", "title": "[Oral contraceptives and trisomy 21. A retrospective study of 730 cases (author's transl)].", "content": "A retrospective study of 730 cases of trisomy 21 and of 1 035 cases of abnormal children without a detectable chromosomal aberration, allows the study of the frequency of use of oral contraceptives by their mothers. The statistical analysis shows no notable differences for mothers 30 years old and younger. Among the mothers 30 to 38 years old, these is an excess of pill-taking by mothers of trisomy 21 children. For this second category of mothers (30 to 38 years) this excess is significant (a) when the delay between the cessation of pill-taking and the conception of the child is six months of less; (b) when the duration of pill-taking has been longer than one year; and (c), when those two factors are present simultaneously. Moreover, the frequency of males is significantly reduced in trisomy 21 children when their mothers have taken the pill. As a whole, for the subsample of mothers 30 and older, a correlation is observed between the three factors analysed, pill-taking, sex ratio, and trisomy 21. In view of the fact that decrease of the sex ratio and the increase of the frequency of trisomy 21 both are correlated with maternal aging in the general population, it seems remarkable that a correlation between these two variables and the use of oral contraceptives is observed only when the women had already passed the first of their reproduction period.", "contents": "[Oral contraceptives and trisomy 21. A retrospective study of 730 cases (author's transl)]. A retrospective study of 730 cases of trisomy 21 and of 1 035 cases of abnormal children without a detectable chromosomal aberration, allows the study of the frequency of use of oral contraceptives by their mothers. The statistical analysis shows no notable differences for mothers 30 years old and younger. Among the mothers 30 to 38 years old, these is an excess of pill-taking by mothers of trisomy 21 children. For this second category of mothers (30 to 38 years) this excess is significant (a) when the delay between the cessation of pill-taking and the conception of the child is six months of less; (b) when the duration of pill-taking has been longer than one year; and (c), when those two factors are present simultaneously. Moreover, the frequency of males is significantly reduced in trisomy 21 children when their mothers have taken the pill. As a whole, for the subsample of mothers 30 and older, a correlation is observed between the three factors analysed, pill-taking, sex ratio, and trisomy 21. In view of the fact that decrease of the sex ratio and the increase of the frequency of trisomy 21 both are correlated with maternal aging in the general population, it seems remarkable that a correlation between these two variables and the use of oral contraceptives is observed only when the women had already passed the first of their reproduction period."} {"id": "PMID:159020", "title": "D-penicillamine and immune complex deposition.", "content": "Dense, granular immunoglobulin deposits have been identified at the epidermo-dermal junction in 4 out of 10 patients who developed toxic reactions to D-penicillamine therapy for rheumatoid arthritis. Three of 4 patients developing a lupus-like syndrome while on penicillamine had similar findings on skin biopsy. Serum immunoglobulin and complement levels decreased significantly in patients treated with penicillamine. It is suggested that, in addition to penicillamine nephropathy, other side effects of this drug may be related to widespread deposition of immune complexes.", "contents": "D-penicillamine and immune complex deposition. Dense, granular immunoglobulin deposits have been identified at the epidermo-dermal junction in 4 out of 10 patients who developed toxic reactions to D-penicillamine therapy for rheumatoid arthritis. Three of 4 patients developing a lupus-like syndrome while on penicillamine had similar findings on skin biopsy. Serum immunoglobulin and complement levels decreased significantly in patients treated with penicillamine. It is suggested that, in addition to penicillamine nephropathy, other side effects of this drug may be related to widespread deposition of immune complexes."} {"id": "PMID:159019", "title": "The Pasteur effect and catabolite repression in an oxidative yeast, Kluyveromyces lactis.", "content": "The presence of the Pasteur effect in Kluyveromyces lactis grown in glucose was shown by azide-stimulated glucose fermentation. Extracts from these cells contained ATP-sensitive phosphofructokinase activity. Cells grown on succinate oxidized glucose slowly at first without azide-stimulated rates of fermentation. Phosphofructokinase in these cells was ATP-insensitive. The activity of NAD+-isocitrate dehydrogenase in cell extracts did not require AMP activation. These results suggested the presence of a Pasteur effect in glucose-grown but not in succinate-grown K. lactis, mediated by (a) ATP inhibition of phosphofructokinase (b) possibly via feedback control of glucose transport, but not by AMP activation of isocitrate dehydrogenase. Azide inhibition of the Pasteur effect during growth of the cells did not lead to catabolite repression of respiratory activity. The results therefore suggest that the Pasteur effect does not inhibit the development of a Crabtree effect in oxidative yeasts.", "contents": "The Pasteur effect and catabolite repression in an oxidative yeast, Kluyveromyces lactis. The presence of the Pasteur effect in Kluyveromyces lactis grown in glucose was shown by azide-stimulated glucose fermentation. Extracts from these cells contained ATP-sensitive phosphofructokinase activity. Cells grown on succinate oxidized glucose slowly at first without azide-stimulated rates of fermentation. Phosphofructokinase in these cells was ATP-insensitive. The activity of NAD+-isocitrate dehydrogenase in cell extracts did not require AMP activation. These results suggested the presence of a Pasteur effect in glucose-grown but not in succinate-grown K. lactis, mediated by (a) ATP inhibition of phosphofructokinase (b) possibly via feedback control of glucose transport, but not by AMP activation of isocitrate dehydrogenase. Azide inhibition of the Pasteur effect during growth of the cells did not lead to catabolite repression of respiratory activity. The results therefore suggest that the Pasteur effect does not inhibit the development of a Crabtree effect in oxidative yeasts."} {"id": "PMID:159021", "title": "Prosepctive analysis of heart biopsies in coronary artery surgery.", "content": "In a prospective analysis of 36 biopsies from human hearts performed at the time of elective coronary operation, several morphological changes were identified in the myocardium. Some of these changes (fibrosis, vacuolation, edema, and amyloid deposition) are of clinical signficance and may affect the long-term prognosis for patients undergoing revascularization procedures. It appears, therefore, that knowledge of the morphological state of the myocardium at the time of operation can prove useful in elucidating further the long-term effects of coronary artery bypass on the left ventricular myocardium.", "contents": "Prosepctive analysis of heart biopsies in coronary artery surgery. In a prospective analysis of 36 biopsies from human hearts performed at the time of elective coronary operation, several morphological changes were identified in the myocardium. Some of these changes (fibrosis, vacuolation, edema, and amyloid deposition) are of clinical signficance and may affect the long-term prognosis for patients undergoing revascularization procedures. It appears, therefore, that knowledge of the morphological state of the myocardium at the time of operation can prove useful in elucidating further the long-term effects of coronary artery bypass on the left ventricular myocardium."} {"id": "PMID:159022", "title": "Immediate operation for ectopia cordis.", "content": "Forty-one infants with thoracoabdominal ectopia cordis have been reported to date; 9 of them survived. Among the patients with an omphalocele as the abdominal wall defect, however, only 2 survived. Death in this group of patients occurred almost exclusively as a consequence of either attempted coverage of the heart or secondary to the associated intracardiac lesion. We report here the case of a patient recently treated in whom coverage with a temporary Silastic prosthesis protected the exposed heart from infection and rupture of the sac, thus permitting full cardiac investigation before operation.", "contents": "Immediate operation for ectopia cordis. Forty-one infants with thoracoabdominal ectopia cordis have been reported to date; 9 of them survived. Among the patients with an omphalocele as the abdominal wall defect, however, only 2 survived. Death in this group of patients occurred almost exclusively as a consequence of either attempted coverage of the heart or secondary to the associated intracardiac lesion. We report here the case of a patient recently treated in whom coverage with a temporary Silastic prosthesis protected the exposed heart from infection and rupture of the sac, thus permitting full cardiac investigation before operation."} {"id": "PMID:159023", "title": "Relationship of endogenous ATP to flagellar beat frequency in ejaculated bull spermatozoa.", "content": "The relationship between endogenous ATP and flagellar beat frequency of bull spermatozoa was investigated using cinematographic and biochemical criteria. ATP content was measured by the luciferin-luciferase method. Potassium, sodium, chloride, and viscosity were used to alter motility to establish the concomitant effects on ATP content. Beat frequency was correlated to endogenous ATP in potassium-supplemented media. Increased sodium concentration was related to ATP content, but not to beat frequency. With increasing viscosity of the medium, the frequency of flagellary beat decreased dramatically, while ATP content of the cells remained unchanged.", "contents": "Relationship of endogenous ATP to flagellar beat frequency in ejaculated bull spermatozoa. The relationship between endogenous ATP and flagellar beat frequency of bull spermatozoa was investigated using cinematographic and biochemical criteria. ATP content was measured by the luciferin-luciferase method. Potassium, sodium, chloride, and viscosity were used to alter motility to establish the concomitant effects on ATP content. Beat frequency was correlated to endogenous ATP in potassium-supplemented media. Increased sodium concentration was related to ATP content, but not to beat frequency. With increasing viscosity of the medium, the frequency of flagellary beat decreased dramatically, while ATP content of the cells remained unchanged."} {"id": "PMID:159024", "title": "[Partial trisomy 21].", "content": "Three mentally retarded children with partial trisomy 21 who looked like children with complete trisomy 21 had increased activity of superoxide dismutase A. This emphases the pathogenic role of the 21q22 band in this condition.", "contents": "[Partial trisomy 21]. Three mentally retarded children with partial trisomy 21 who looked like children with complete trisomy 21 had increased activity of superoxide dismutase A. This emphases the pathogenic role of the 21q22 band in this condition."} {"id": "PMID:159026", "title": "The environment as a support system for independent living.", "content": "In extended interviews and visits with 150 physically disabled young adults living independently in Berkeley, CA, the author studied the environment as they experienced it and evaluated its accommodation to their special needs. The environment in this study is considered in physical and psychosocial terms, that is, as a support system for the multifaceted needs of the whole person. The framework for organizing the data was Mayer Spivak's construct of \"archetypal place\" in which he defines 13 fundamental places in terms of the behaviors they support: shelter, sleep, mate, groom, feed, excrete, store, territory, play, route, meet, compete, and work. For purposes of the present work, shelter and mate are discussed--shelter, because of the clarity of its relationship between existence and physical form, and mate because of its more abstract relevance to physical form.", "contents": "The environment as a support system for independent living. In extended interviews and visits with 150 physically disabled young adults living independently in Berkeley, CA, the author studied the environment as they experienced it and evaluated its accommodation to their special needs. The environment in this study is considered in physical and psychosocial terms, that is, as a support system for the multifaceted needs of the whole person. The framework for organizing the data was Mayer Spivak's construct of \"archetypal place\" in which he defines 13 fundamental places in terms of the behaviors they support: shelter, sleep, mate, groom, feed, excrete, store, territory, play, route, meet, compete, and work. For purposes of the present work, shelter and mate are discussed--shelter, because of the clarity of its relationship between existence and physical form, and mate because of its more abstract relevance to physical form."} {"id": "PMID:159027", "title": "Iliolumbar syndrome as a common cause of low back pain: diagnosis and prognosis.", "content": "Most cases of low back pain fall into the category of nonspecific low back pain in which no specific pathology can be detected by x-ray, laboratory tests, or biopsy. In the authors' experience about 50% of the patients falling into this group have a clinical picture characterized by symptoms and signs localized at one iliac crest. The symptoms can be abolished temporarily by infiltration of the posterior iliac crest with lidocaine. Because of the location of the findings and the unknown etiology the term iliolumbar syndrome is suggested. Distinguishing the iliolumbar syndrome from the root irritation syndrome may avoid unnecessary surgery. Chronic iliolumbar syndrome is a frequent cause of permanent low back disability, a fact not commonly recognized.", "contents": "Iliolumbar syndrome as a common cause of low back pain: diagnosis and prognosis. Most cases of low back pain fall into the category of nonspecific low back pain in which no specific pathology can be detected by x-ray, laboratory tests, or biopsy. In the authors' experience about 50% of the patients falling into this group have a clinical picture characterized by symptoms and signs localized at one iliac crest. The symptoms can be abolished temporarily by infiltration of the posterior iliac crest with lidocaine. Because of the location of the findings and the unknown etiology the term iliolumbar syndrome is suggested. Distinguishing the iliolumbar syndrome from the root irritation syndrome may avoid unnecessary surgery. Chronic iliolumbar syndrome is a frequent cause of permanent low back disability, a fact not commonly recognized."} {"id": "PMID:159028", "title": "Dilation of synthetic grafts and junctional aneurysms.", "content": "Dilation of prosthetic graft has been noted by authors in association with junctional aneurysm between the synthetic graft and host arteries. Dilation of graft materials was suspected as one of the etiologic factors of the junctional aneurysm. Increase in transverse diameter was observed as early as a few minutes to five years postimplantation in clinical cases. The phenomenon of dilation was studied experimentally. Nine different types of graft materials were tested using intraluminal pulse pressure of 100/60 mm Hg, and the transverse diameters were measured at various time intervals. Knitted grafts showed the more pronounced changes compared with the woven. Degree of dilation differed considerably among the different types of knitted grafts.", "contents": "Dilation of synthetic grafts and junctional aneurysms. Dilation of prosthetic graft has been noted by authors in association with junctional aneurysm between the synthetic graft and host arteries. Dilation of graft materials was suspected as one of the etiologic factors of the junctional aneurysm. Increase in transverse diameter was observed as early as a few minutes to five years postimplantation in clinical cases. The phenomenon of dilation was studied experimentally. Nine different types of graft materials were tested using intraluminal pulse pressure of 100/60 mm Hg, and the transverse diameters were measured at various time intervals. Knitted grafts showed the more pronounced changes compared with the woven. Degree of dilation differed considerably among the different types of knitted grafts."} {"id": "PMID:159031", "title": "[Localization of ATPase in the cerebral cortex and its role in the functional activity of neurons].", "content": "By analogy of defensive conditioned reflex formation in rats using a cytochemical method, dependency of localization and concentration of the product of ATP-ase activity on neuronal and synaptic functional activity has been demonstrated. It corresponds to the notion that only a part of the cortical cells are simultaneously at the state of structural-functional activity. The experimental data demonstrate that the CNS excitation in the animals during the process of learning is connected with increasing ATP-ase activity in ultrastructures of the nucleolus, pericaryon and synapses of some neurons participating in the formation of trace processes in the brain.", "contents": "[Localization of ATPase in the cerebral cortex and its role in the functional activity of neurons]. By analogy of defensive conditioned reflex formation in rats using a cytochemical method, dependency of localization and concentration of the product of ATP-ase activity on neuronal and synaptic functional activity has been demonstrated. It corresponds to the notion that only a part of the cortical cells are simultaneously at the state of structural-functional activity. The experimental data demonstrate that the CNS excitation in the animals during the process of learning is connected with increasing ATP-ase activity in ultrastructures of the nucleolus, pericaryon and synapses of some neurons participating in the formation of trace processes in the brain."} {"id": "PMID:159032", "title": "[Formation of the circulatory bed of the neuromuscular spindles in forearm and hand muscles].", "content": "The data are presented on the formation and main constitutional principles in the blood supply of the neuromuscular spindles in the human forearm and hand during embryogenesis and early postnatal life. It has been stated that the neuromuscular spindles posses their own microcirculatory bed which is formed by the vessels of the surrounding muscular tissue, tends to separate in the course of development and subdivides into two parts: extracapsular and intracapsular. The vessels of the extracapsular part form dense capillary nets on the external surface of the capsule and follow extracapsular parts of the intrafusal muscular fibres. The intracapsular vessels either cover the internal surface of the capsule, or adjoin the intrafusal muscular fibres, or else run in the free subcapsular space.", "contents": "[Formation of the circulatory bed of the neuromuscular spindles in forearm and hand muscles]. The data are presented on the formation and main constitutional principles in the blood supply of the neuromuscular spindles in the human forearm and hand during embryogenesis and early postnatal life. It has been stated that the neuromuscular spindles posses their own microcirculatory bed which is formed by the vessels of the surrounding muscular tissue, tends to separate in the course of development and subdivides into two parts: extracapsular and intracapsular. The vessels of the extracapsular part form dense capillary nets on the external surface of the capsule and follow extracapsular parts of the intrafusal muscular fibres. The intracapsular vessels either cover the internal surface of the capsule, or adjoin the intrafusal muscular fibres, or else run in the free subcapsular space."} {"id": "PMID:159035", "title": "[Morphogenesis of immune complex glomerulonephritis].", "content": "Morphological changes in the kidneys in nonspecific ulcerative colitis were studied and the following variants of the kidney involvement were established: (1) allergic changes manifested by membraneous and mesangio-proliferative glomerulonephritis, renal vasculitis, phenomena of stromal desorganization with lymphoid and histiocyte infiltrations; (2) metabolic changes manifested by various kinds of degeneration of the tubular apparatus including changes typical of potassium-deficient nephropathy; (3) toxic -- necrotic nephrosis and (4) infectious -- nonsuppurative and suppurative interstitial nephritis.", "contents": "[Morphogenesis of immune complex glomerulonephritis]. Morphological changes in the kidneys in nonspecific ulcerative colitis were studied and the following variants of the kidney involvement were established: (1) allergic changes manifested by membraneous and mesangio-proliferative glomerulonephritis, renal vasculitis, phenomena of stromal desorganization with lymphoid and histiocyte infiltrations; (2) metabolic changes manifested by various kinds of degeneration of the tubular apparatus including changes typical of potassium-deficient nephropathy; (3) toxic -- necrotic nephrosis and (4) infectious -- nonsuppurative and suppurative interstitial nephritis."} {"id": "PMID:159038", "title": "The dental care of handicapped children in South Australia.", "content": "Sixty-two per cent of handicapped children had a dentist willing to provide treatment; 55 per cent and 41 per cent were examined and were treated at least annually. Approximately 58 per cent were reported by their guardians to be manageable in general dental practice. Treatment was provided under general anaesthesia for 29 per cent of the children, although 39 per cent were considered by their guardians to require this procedure. Factors related to type and frequency of dental treatment are discussed.", "contents": "The dental care of handicapped children in South Australia. Sixty-two per cent of handicapped children had a dentist willing to provide treatment; 55 per cent and 41 per cent were examined and were treated at least annually. Approximately 58 per cent were reported by their guardians to be manageable in general dental practice. Treatment was provided under general anaesthesia for 29 per cent of the children, although 39 per cent were considered by their guardians to require this procedure. Factors related to type and frequency of dental treatment are discussed."} {"id": "PMID:159039", "title": "Post-mortem electrical stimulation of muscle and its effects on sarcoplasmic reticulum adenosine triphosphatase.", "content": "Sarcoplasmic reticulum (SR) was isolated from control muscles and from muscles which had been subjected to short-term post-mortem electrical stimulation. Both preparations had similar protein compositions but the SR from electrically stimulated muscle had a lower 'extra' ATPase activity. The ability of the SR preparations from electrically stimulated muscles to accumulate Ca2+ was about the same as the controls. There was, therefore, an apparently greater efficiency of Ca2+ transport in the isolated vesicles, the reason for which is not known, but an alteration in the 'leakiness' of the membrane may be involved. Purified ATPase isolated from control and stimulated SR contained, in addition to the ATPase protein, a polypeptide of molecular weight about 30 000. The purified ATPase vesicles from electrically stimulated muscle had a reduced activity as measured by ATP splitting activity, phosphoenzyme formation from either inorganic orthophosphate (Pi) or ATP, or by an ATP in equilibrium Pi exchange reaction. These reduced activities probably result from an alteration in the binding affinities of the ATPase for ATP and Pi. The low affinity site for calcium binding was not affected by electrical stimulation. Purified ATPase vesicles from stimulated muscle were more susceptible to proteolytic attack, suggesting that the conformation of the protein or its association with the membrane lipids had been altered.", "contents": "Post-mortem electrical stimulation of muscle and its effects on sarcoplasmic reticulum adenosine triphosphatase. Sarcoplasmic reticulum (SR) was isolated from control muscles and from muscles which had been subjected to short-term post-mortem electrical stimulation. Both preparations had similar protein compositions but the SR from electrically stimulated muscle had a lower 'extra' ATPase activity. The ability of the SR preparations from electrically stimulated muscles to accumulate Ca2+ was about the same as the controls. There was, therefore, an apparently greater efficiency of Ca2+ transport in the isolated vesicles, the reason for which is not known, but an alteration in the 'leakiness' of the membrane may be involved. Purified ATPase isolated from control and stimulated SR contained, in addition to the ATPase protein, a polypeptide of molecular weight about 30 000. The purified ATPase vesicles from electrically stimulated muscle had a reduced activity as measured by ATP splitting activity, phosphoenzyme formation from either inorganic orthophosphate (Pi) or ATP, or by an ATP in equilibrium Pi exchange reaction. These reduced activities probably result from an alteration in the binding affinities of the ATPase for ATP and Pi. The low affinity site for calcium binding was not affected by electrical stimulation. Purified ATPase vesicles from stimulated muscle were more susceptible to proteolytic attack, suggesting that the conformation of the protein or its association with the membrane lipids had been altered."} {"id": "PMID:159040", "title": "The management of gastroschisis.", "content": "A review of gastroschisis treated at the Royal Alexandra Hospital for Children, Sydney, in the ten years between 1967 and 1976, was carried out. Early postoperative deaths occurred in those with poor general condition before and immediately after the operation. The presence of a gastrostomy appears to be most effective in the immediate postoperative period to assist in decreasing intraabdominal pressure. The results of three initial operative methods are discussed. The three procedures are the Gross method; prosthetic closure; and the Savage and Davey method of transverse incision and closure. The purpose of this paper is to suggest that the procedure described by Savage and Davey has been a most successful procedure in providing reliable and safe method of closure of gastroschisis, avoiding the complications and morbidity of staged closure using prosthetic material.", "contents": "The management of gastroschisis. A review of gastroschisis treated at the Royal Alexandra Hospital for Children, Sydney, in the ten years between 1967 and 1976, was carried out. Early postoperative deaths occurred in those with poor general condition before and immediately after the operation. The presence of a gastrostomy appears to be most effective in the immediate postoperative period to assist in decreasing intraabdominal pressure. The results of three initial operative methods are discussed. The three procedures are the Gross method; prosthetic closure; and the Savage and Davey method of transverse incision and closure. The purpose of this paper is to suggest that the procedure described by Savage and Davey has been a most successful procedure in providing reliable and safe method of closure of gastroschisis, avoiding the complications and morbidity of staged closure using prosthetic material."} {"id": "PMID:159042", "title": "Isolation and partial characterization of magnesium ion- and calcium ion-dependent adenosine triphosphatase activity from bovine brain microsomal fraction.", "content": "Microsomal fraction was prepared by ultracentrifugation of homogenates of cortical tissue from bovine brains. The preparation displayed ATPase (adenosine triphosphatase) activity in the presence of Mg(2+) (6.4mumol of P(i)/h per mg of protein) and Ca(2+) (3.4mumol of P(i)/h per mg of protein). Kinetic analysis of the activation of the enzyme preparation by Ca(2+) resulted in the demonstration of two apparent K(m) values for Ca(2+) (6.0x10(-8)m and 1.2x10(-6)m). Treatment of the microsomal membranes with Triton X-100 resulted in solubilization of the ATPase, though with some loss of activity. The solubilized microsomal proteins were incorporated into liposomes. By incubation of the liposomes in media containing (45)Ca(2+) an ATP-dependent uptake of Ca(2+) was demonstrated. The solubilized preparation was subjected to preparative isoelectric focusing in granulated gel beds. Two distinct peaks of Mg(2+)- and Ca(2+)-dependent ATPase activity were observed at pH4.8 (peak 4.8) and at pH6.3 (peak 6.3). The material isolated in peaks 4.8 and 6.3 was focused in polyacrylamide gel with pH gradients. The material corresponding to peak 4.8 consisted of a single protein, whereas peak 6.3 contained one major and at least one minor protein. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis confirmed these results and indicated that the major component of peak 4.8 and the protein of peak 6.3 both had a molecular weight of 105000. The material in peaks 4.8 and 6.3 was assayed for ATPase activity in the presence of various concentrations of Ca(2+). Kinetic analysis of the results for peak 4.8 demonstrated an apparent K(m) value for Ca(2+) of 4.1x10(-8)m. The enzyme isolated at pH6.3 had an apparent K(m) value of 3.8x10(-6)m. However, when the material from peak 4.8 was incubated in the presence of 1mm-Mg(2+) the ATPase could not be activated by Ca(2+).", "contents": "Isolation and partial characterization of magnesium ion- and calcium ion-dependent adenosine triphosphatase activity from bovine brain microsomal fraction. Microsomal fraction was prepared by ultracentrifugation of homogenates of cortical tissue from bovine brains. The preparation displayed ATPase (adenosine triphosphatase) activity in the presence of Mg(2+) (6.4mumol of P(i)/h per mg of protein) and Ca(2+) (3.4mumol of P(i)/h per mg of protein). Kinetic analysis of the activation of the enzyme preparation by Ca(2+) resulted in the demonstration of two apparent K(m) values for Ca(2+) (6.0x10(-8)m and 1.2x10(-6)m). Treatment of the microsomal membranes with Triton X-100 resulted in solubilization of the ATPase, though with some loss of activity. The solubilized microsomal proteins were incorporated into liposomes. By incubation of the liposomes in media containing (45)Ca(2+) an ATP-dependent uptake of Ca(2+) was demonstrated. The solubilized preparation was subjected to preparative isoelectric focusing in granulated gel beds. Two distinct peaks of Mg(2+)- and Ca(2+)-dependent ATPase activity were observed at pH4.8 (peak 4.8) and at pH6.3 (peak 6.3). The material isolated in peaks 4.8 and 6.3 was focused in polyacrylamide gel with pH gradients. The material corresponding to peak 4.8 consisted of a single protein, whereas peak 6.3 contained one major and at least one minor protein. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis confirmed these results and indicated that the major component of peak 4.8 and the protein of peak 6.3 both had a molecular weight of 105000. The material in peaks 4.8 and 6.3 was assayed for ATPase activity in the presence of various concentrations of Ca(2+). Kinetic analysis of the results for peak 4.8 demonstrated an apparent K(m) value for Ca(2+) of 4.1x10(-8)m. The enzyme isolated at pH6.3 had an apparent K(m) value of 3.8x10(-6)m. However, when the material from peak 4.8 was incubated in the presence of 1mm-Mg(2+) the ATPase could not be activated by Ca(2+)."} {"id": "PMID:159057", "title": "[Long term effect of ipratropium bromide on gastric secretion].", "content": "In a randomised clinical trial in 10 patients, the effects of a new anticholinergic, 8-isopropyl-3 alpha-DL-tropoyloxy-1 alpha H, 5 alpha H-tropanium hydroxide (ipratropiumbromide, active principle of Atrovent), on pentagastrin-stimulated gastric secretion was investigated. The study was performed in comparison to placebo, using the double-blind technique. Each patient served as his/her own control. As earlier test results seemed to indicate that ipratropium bromide had a particularly long duration of action, the special aim of the trial was to clarify whether an oral dose of 30 mg of the product inhibits gastric secretion for more than 11 h after administration. The findings show that basal acid secretion (BAO) was significantly reduced 11 ts following placebo. On the other hand, upon determination of maximum acid secretion (MAO) 12--13 h following administration, there was no difference between the anticholinergic and placebo. The results of the study of the study are discussed.", "contents": "[Long term effect of ipratropium bromide on gastric secretion]. In a randomised clinical trial in 10 patients, the effects of a new anticholinergic, 8-isopropyl-3 alpha-DL-tropoyloxy-1 alpha H, 5 alpha H-tropanium hydroxide (ipratropiumbromide, active principle of Atrovent), on pentagastrin-stimulated gastric secretion was investigated. The study was performed in comparison to placebo, using the double-blind technique. Each patient served as his/her own control. As earlier test results seemed to indicate that ipratropium bromide had a particularly long duration of action, the special aim of the trial was to clarify whether an oral dose of 30 mg of the product inhibits gastric secretion for more than 11 h after administration. The findings show that basal acid secretion (BAO) was significantly reduced 11 ts following placebo. On the other hand, upon determination of maximum acid secretion (MAO) 12--13 h following administration, there was no difference between the anticholinergic and placebo. The results of the study of the study are discussed."} {"id": "PMID:159058", "title": "Additional pharmacological aspects of orgotein, a metalloprotein with superoxide-dismutase activity.", "content": "Orgotein is a copper- and zinc-containing protein with superoxide-dismutase activity which can be isolated from bovine liver and erythrocytes. The effects of this drug on adjuvant -induced arthritis in rats, and particularly on the changes in erythrocytes sedimentation rates and plasma fibrinogen levels induced by this experimental infection, were studied. Orgotein was also assayed on nystatin-induced paw edema, passive cutaneous anaphylaxis and Arthus reaction, in rats. Finally, studies on platelet aggregation and the prostaglandin system were conducted. Given at doses of 2.5 and 5 mg/kg i.p. for 14 days to arthritic rats, orgotein normalized the serum changes, inhibited the foot swelling and improved the performance time on the rotating bar. The drug reduced, after a single dose, the nystatin-induced edema, whilst it showed no effects on the immunological inflammations, platelet aggregation and prostaglandin system. The probable mechanism of action is discussed.", "contents": "Additional pharmacological aspects of orgotein, a metalloprotein with superoxide-dismutase activity. Orgotein is a copper- and zinc-containing protein with superoxide-dismutase activity which can be isolated from bovine liver and erythrocytes. The effects of this drug on adjuvant -induced arthritis in rats, and particularly on the changes in erythrocytes sedimentation rates and plasma fibrinogen levels induced by this experimental infection, were studied. Orgotein was also assayed on nystatin-induced paw edema, passive cutaneous anaphylaxis and Arthus reaction, in rats. Finally, studies on platelet aggregation and the prostaglandin system were conducted. Given at doses of 2.5 and 5 mg/kg i.p. for 14 days to arthritic rats, orgotein normalized the serum changes, inhibited the foot swelling and improved the performance time on the rotating bar. The drug reduced, after a single dose, the nystatin-induced edema, whilst it showed no effects on the immunological inflammations, platelet aggregation and prostaglandin system. The probable mechanism of action is discussed."} {"id": "PMID:159067", "title": "Morbidity in gynaecological day-case surgery. A comparison of two anaesthetic techniques.", "content": "The effectiveness of fentanyl, given as part of the anaesthetic technique, in reducing abdominal pain following outpatient gynaecological surgery has been examined. It was found to reduce significantly the frequency of abdominal pain in the period extending from discharge from hospital to the first evening, while not compromising surgical conditions nor increasing the frequency of other post-operative sequelae such as nausea and vomiting.", "contents": "Morbidity in gynaecological day-case surgery. A comparison of two anaesthetic techniques. The effectiveness of fentanyl, given as part of the anaesthetic technique, in reducing abdominal pain following outpatient gynaecological surgery has been examined. It was found to reduce significantly the frequency of abdominal pain in the period extending from discharge from hospital to the first evening, while not compromising surgical conditions nor increasing the frequency of other post-operative sequelae such as nausea and vomiting."} {"id": "PMID:159068", "title": "Comparison of anti-pollution modifications of Mapleson A and D anaesthetic systems.", "content": "Hafnia A and Hafnia D anaesthetic systems are non-polluting modifications of the Mapleson A and D systems. The excess gas is vented in the Hafnia systems directly and continuously via a calibrated ejector flowmeter. Sixteen adult patients anaesthetized for abdominal surgery were ventilated and either Hafnia A or D systems at six different fresh gas flows. No difference between the Hafnia A and D systems could be demonstrated in the values of arterial carbon dioxide tension measured with the same fresh gas flow, despite gas flows in opposite directions.", "contents": "Comparison of anti-pollution modifications of Mapleson A and D anaesthetic systems. Hafnia A and Hafnia D anaesthetic systems are non-polluting modifications of the Mapleson A and D systems. The excess gas is vented in the Hafnia systems directly and continuously via a calibrated ejector flowmeter. Sixteen adult patients anaesthetized for abdominal surgery were ventilated and either Hafnia A or D systems at six different fresh gas flows. No difference between the Hafnia A and D systems could be demonstrated in the values of arterial carbon dioxide tension measured with the same fresh gas flow, despite gas flows in opposite directions."} {"id": "PMID:159069", "title": "Contrasts in the actions of protein antibiotics on deoxyribonucleic acid structure and function.", "content": "The protein antibiotics neocarzinostain (NCS), macromomycin (MCR), and auromomycin (AUR), which is closely related to MCR, have been compared for their in vitro and in vivo actions on deoxyribonucleic acid (DNA). NCS, markedly stimulated by 2-mercaptoethanol, is much more active in inducing strand scissions in superhelical pMB9 and linear duplex lambda DNA than AUR, which is slightly inhibited by 2-mercaptoethanol. Purified MCR, even at very high levels, does not give any significant amount of cutting with either DNA substrate. 2-Propanol stimulates the activity of NCS but inhibits that of AUR. On the other hand, the antioxidant alpha-tocopherol strongly inhibits DNA breakage by both drugs. The intercalating drugs ethidium bromide, daunorubicin, proflavin, and actinomycin D at low concentrations inhibit DNA scission by AUR. The levels of intercalators required to inhibit NCS activity to comparable levels are about 10 times higher than those for AUR. Although MCR has virtually no in vitro DNA cutting activity, it is, like AUR and NCS, cytotoxic, as measured by the inhibition of DNA synthesis and induction of DNA strand breakage in HeLa cells.", "contents": "Contrasts in the actions of protein antibiotics on deoxyribonucleic acid structure and function. The protein antibiotics neocarzinostain (NCS), macromomycin (MCR), and auromomycin (AUR), which is closely related to MCR, have been compared for their in vitro and in vivo actions on deoxyribonucleic acid (DNA). NCS, markedly stimulated by 2-mercaptoethanol, is much more active in inducing strand scissions in superhelical pMB9 and linear duplex lambda DNA than AUR, which is slightly inhibited by 2-mercaptoethanol. Purified MCR, even at very high levels, does not give any significant amount of cutting with either DNA substrate. 2-Propanol stimulates the activity of NCS but inhibits that of AUR. On the other hand, the antioxidant alpha-tocopherol strongly inhibits DNA breakage by both drugs. The intercalating drugs ethidium bromide, daunorubicin, proflavin, and actinomycin D at low concentrations inhibit DNA scission by AUR. The levels of intercalators required to inhibit NCS activity to comparable levels are about 10 times higher than those for AUR. Although MCR has virtually no in vitro DNA cutting activity, it is, like AUR and NCS, cytotoxic, as measured by the inhibition of DNA synthesis and induction of DNA strand breakage in HeLa cells."} {"id": "PMID:159071", "title": "Fluorescence energy transfer between subfragment-1 and actin points in the rigor complex of actosubfragment-1.", "content": "The fast-reacting thiol (SH1) of myosin subfragment-1 (S-1) was covalently and specifically labeled with (iodoacetamido)fluorescein (IAF), while Cys-373 of actin was also covalently and preferentially labeled with N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine (1,5-IAEDANS). The method of fluorescence energy transfer was used to examine the spatial proximity between the two sites, i.e., SH1 and Cys-373, in the rigor complex of acto-S-1. Approximately 30% fluorescence energy transfer was observed from the 1,5-IAEDANS on actin as a donor to the IAF on S-1 as an acceptor in their rigor complex; under certain assumptions this corresponds to a distance of ca. 6.0 nm.", "contents": "Fluorescence energy transfer between subfragment-1 and actin points in the rigor complex of actosubfragment-1. The fast-reacting thiol (SH1) of myosin subfragment-1 (S-1) was covalently and specifically labeled with (iodoacetamido)fluorescein (IAF), while Cys-373 of actin was also covalently and preferentially labeled with N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine (1,5-IAEDANS). The method of fluorescence energy transfer was used to examine the spatial proximity between the two sites, i.e., SH1 and Cys-373, in the rigor complex of acto-S-1. Approximately 30% fluorescence energy transfer was observed from the 1,5-IAEDANS on actin as a donor to the IAF on S-1 as an acceptor in their rigor complex; under certain assumptions this corresponds to a distance of ca. 6.0 nm."} {"id": "PMID:159072", "title": "Rapid kinetics of calcium ion transport and ATPase activity in the sarcoplasmic reticulum of dystrophic muscle.", "content": "Vesicular fragments of sarcoplasmic reticulum were isolated from pectoralis muscle of normal and dystrophic chicken. Purification of both preparations was equally satisfactory, as shown by a prominent ATPase band in electrophoresis gels. Measurements of ATPase phosphorylation, Ca2+ transport and Pi cleavage by rapid quench methods revealed a lower specific activity of the dystrophic vesicles with respect to all of these functions. On the other hand, Ca2+-independent ATPase activity was found to be increased in dystrophic vesicles. It is suggested that a fraction of ATPase units of dystrophic sarcoplasmic reticulum is not activated by Ca2+, owing to an altered protein assembly within the membrane bilayer. In fact, when the membrane structure is perturbed by detergents normal and dystropic preparations acquire an equally high Ca2+-dependent ATPase.", "contents": "Rapid kinetics of calcium ion transport and ATPase activity in the sarcoplasmic reticulum of dystrophic muscle. Vesicular fragments of sarcoplasmic reticulum were isolated from pectoralis muscle of normal and dystrophic chicken. Purification of both preparations was equally satisfactory, as shown by a prominent ATPase band in electrophoresis gels. Measurements of ATPase phosphorylation, Ca2+ transport and Pi cleavage by rapid quench methods revealed a lower specific activity of the dystrophic vesicles with respect to all of these functions. On the other hand, Ca2+-independent ATPase activity was found to be increased in dystrophic vesicles. It is suggested that a fraction of ATPase units of dystrophic sarcoplasmic reticulum is not activated by Ca2+, owing to an altered protein assembly within the membrane bilayer. In fact, when the membrane structure is perturbed by detergents normal and dystropic preparations acquire an equally high Ca2+-dependent ATPase."} {"id": "PMID:159073", "title": "DNA damage and repair in relation to cell killing in neocarzinostatin-treated HeLa cells.", "content": "To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug.", "contents": "DNA damage and repair in relation to cell killing in neocarzinostatin-treated HeLa cells. To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug."} {"id": "PMID:159074", "title": "Strand scission of superhelical and linear duplex DNAs by the antitumor protein macromomycin. Relationship of in vitro DNA damage to cell growth inhibition.", "content": "Macromomycin, a protein antitumor drug, was found to cause strand scissions in vitro in superhelical PM2 and SV40 DNA as well as linear duplex lambda DNA. DNA damage appeared to be single rather than double-strand scissions, and there is an indication that DNA breaks occur at some preferential base sites. The DNA breaks were predominantly true single-strand scissions as opposed to alkali-labile bonds. The cutting reaction was inhibited by low temperature (0 degrees C) and reached a maximum at 45 degrees C. The reaction was not affected by 2-mercaptoethanol, although EDTA did cause a slight decrease in the reaction rate. MgCl2 was found to be an effective inhibitor of the strand scission activity of the drug. The rate of DNA cutting was linear over a wide range of DNA substrate levels. There appeared to be a correlation between the drug's ability to damage DNA and to inhibit cell growth in that similar losses of these two activities occurred as the drug was thermally denatured.", "contents": "Strand scission of superhelical and linear duplex DNAs by the antitumor protein macromomycin. Relationship of in vitro DNA damage to cell growth inhibition. Macromomycin, a protein antitumor drug, was found to cause strand scissions in vitro in superhelical PM2 and SV40 DNA as well as linear duplex lambda DNA. DNA damage appeared to be single rather than double-strand scissions, and there is an indication that DNA breaks occur at some preferential base sites. The DNA breaks were predominantly true single-strand scissions as opposed to alkali-labile bonds. The cutting reaction was inhibited by low temperature (0 degrees C) and reached a maximum at 45 degrees C. The reaction was not affected by 2-mercaptoethanol, although EDTA did cause a slight decrease in the reaction rate. MgCl2 was found to be an effective inhibitor of the strand scission activity of the drug. The rate of DNA cutting was linear over a wide range of DNA substrate levels. There appeared to be a correlation between the drug's ability to damage DNA and to inhibit cell growth in that similar losses of these two activities occurred as the drug was thermally denatured."} {"id": "PMID:159075", "title": "ATPase and alkaline phosphatase activities of chick and rat small intestinal mucosa.", "content": "The alkaline phosphatase and (Ca2+ +Mg2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) of chick and rat small intestine have been investigated. The same pH optimum was found for membrane-bound and solubilized alkaline phosphatase, whereas those of the corresponding ATPases differed. The solubilised ATPases had inhibition and activation characteristics similar to those of alkaline phosphatase but markedly different from those of the membrane-bound ATPase. These results suggest that membrane-bound alkaline phosphatase and ATPase are not the same enzyme.", "contents": "ATPase and alkaline phosphatase activities of chick and rat small intestinal mucosa. The alkaline phosphatase and (Ca2+ +Mg2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) of chick and rat small intestine have been investigated. The same pH optimum was found for membrane-bound and solubilized alkaline phosphatase, whereas those of the corresponding ATPases differed. The solubilised ATPases had inhibition and activation characteristics similar to those of alkaline phosphatase but markedly different from those of the membrane-bound ATPase. These results suggest that membrane-bound alkaline phosphatase and ATPase are not the same enzyme."} {"id": "PMID:159076", "title": "[Exogenous orthophosphate regulation of ATPase activity of E. coli cells].", "content": "The effect of exogenous orthophosphate and mutations in genes, regulating the Pi transport system, on the ATPase activity of E. coli subcellular fractions was studied. It was shown that the orthophosphate starvation resulted in the cessation of the increase in the ATPase activity of membranes and was accompanied by the increase in the analogous activity of a soluble fraction at the expense of the derepression of alkaline phosphatase possessing this activity. The disturbance, resulted from the mutation of protein components participating in the specific binding and transport of orthophosphate, changed the ATPase activity of subcellular fractions: increased the ATPase activity of soluble fraction (independently of the presence of orthophosphate in medium), did not affect significantly the activity of membrane--bound ATPase in the presence of orthophosphate and decreased this activity in the absence of orthophosphate. The data obtained point to the fact that components, binding exogenous orthophosphate and transporting it into a cell, affect the rigidity of the ATPase bound E. coli cytoplasmic membrane. Mutations resulting in the defect in these components relax this bound and lead to the detection of ATPase proper in the periplasm.", "contents": "[Exogenous orthophosphate regulation of ATPase activity of E. coli cells]. The effect of exogenous orthophosphate and mutations in genes, regulating the Pi transport system, on the ATPase activity of E. coli subcellular fractions was studied. It was shown that the orthophosphate starvation resulted in the cessation of the increase in the ATPase activity of membranes and was accompanied by the increase in the analogous activity of a soluble fraction at the expense of the derepression of alkaline phosphatase possessing this activity. The disturbance, resulted from the mutation of protein components participating in the specific binding and transport of orthophosphate, changed the ATPase activity of subcellular fractions: increased the ATPase activity of soluble fraction (independently of the presence of orthophosphate in medium), did not affect significantly the activity of membrane--bound ATPase in the presence of orthophosphate and decreased this activity in the absence of orthophosphate. The data obtained point to the fact that components, binding exogenous orthophosphate and transporting it into a cell, affect the rigidity of the ATPase bound E. coli cytoplasmic membrane. Mutations resulting in the defect in these components relax this bound and lead to the detection of ATPase proper in the periplasm."} {"id": "PMID:159077", "title": "[Inactivation of factor X by plasmin].", "content": "Plasmin does not activate factor X into the enzyme--factor Xa. On the contrary, the enzyme inactivates factor X, rendering it incapable of conversion into factor Xa during incubation in 25% sodium citrate. After proteolysis by plasmin the prothrombin preparations contaminated with factor X lose their ability to generate thrombin. This ability is partially restored by an addition of factor X.", "contents": "[Inactivation of factor X by plasmin]. Plasmin does not activate factor X into the enzyme--factor Xa. On the contrary, the enzyme inactivates factor X, rendering it incapable of conversion into factor Xa during incubation in 25% sodium citrate. After proteolysis by plasmin the prothrombin preparations contaminated with factor X lose their ability to generate thrombin. This ability is partially restored by an addition of factor X."} {"id": "PMID:159078", "title": "[Energy-dependent uptake of phenazinemethosulfate in isolated chloroplasts].", "content": "The concentration and absorption of methylphenazinium cations (MP+) in suspensions of pea chloroplasts are simultaneously lowered during rapid (approximately 10s) illumination. The light-induced changes of absorption and concentration of MP+ reveal similar sensitivity towards some inhibitors and uncouplers and are determined by MP+ uptake by the thylakoids. The time-course of light-induced MP+ uptake was found to be modified in the presence of dithioerythritol, Mg2+ and ATP, i. e. under conditions which induce the ATPase activity and ATP hydrolysis in chloroplasts. The kinetic curve of light-induced MP+ uptake under these conditions consists of a relatively fast (approximatley 10 s) and a slow (approximately 10 min) components. The slow ATP-dependent component of MP+ uptake is enhanced by low concentrations of gramicidin and is completely inhibited by the energy transfer inhibitor--dicyclohexylcarbodiimide. The data obtained suggest that the light-induced energization of the chloroplast membrane is accompanied by the transport of MP+ into the thylakoids against the electrical potential and concentration gradients.", "contents": "[Energy-dependent uptake of phenazinemethosulfate in isolated chloroplasts]. The concentration and absorption of methylphenazinium cations (MP+) in suspensions of pea chloroplasts are simultaneously lowered during rapid (approximately 10s) illumination. The light-induced changes of absorption and concentration of MP+ reveal similar sensitivity towards some inhibitors and uncouplers and are determined by MP+ uptake by the thylakoids. The time-course of light-induced MP+ uptake was found to be modified in the presence of dithioerythritol, Mg2+ and ATP, i. e. under conditions which induce the ATPase activity and ATP hydrolysis in chloroplasts. The kinetic curve of light-induced MP+ uptake under these conditions consists of a relatively fast (approximatley 10 s) and a slow (approximately 10 min) components. The slow ATP-dependent component of MP+ uptake is enhanced by low concentrations of gramicidin and is completely inhibited by the energy transfer inhibitor--dicyclohexylcarbodiimide. The data obtained suggest that the light-induced energization of the chloroplast membrane is accompanied by the transport of MP+ into the thylakoids against the electrical potential and concentration gradients."} {"id": "PMID:159079", "title": "Quantification of muscle tremor of Huntington's disease patients and their offspring in an early detection study.", "content": "Accelerometer measurements of muscle tremor yielded significant findings for both Huntington's disease (HD) patients and their genetically at risk offspring. Although affected individuals are usually characterized by gross involuntary muscle movements, alterations in minute muscle tremor were also found in our sample of ten HD patients. Irregularities in tremor patterns were intensified with increased time since onset of the disorder and in addition reflected the effects of drug therapy for those on medication. The use of accelerometer measurements of muscle tremor may therefore, prove to be useful in evaluating new medications for affected individuals. For high risk immediate family members currently there is no safe and reliable method to identify, prior to clinical onset, any among them who will develop HD. Aberrant muscle tremor patterns resembling that shown by HD patients were found in one-third of a sample of 15 genetically at risk offspring. In the event an effective method of treatment is developed, early recognition of HD gene carriers by accelerometer tremor measurement could result in control of the disorder prior to substantial neurological damage.", "contents": "Quantification of muscle tremor of Huntington's disease patients and their offspring in an early detection study. Accelerometer measurements of muscle tremor yielded significant findings for both Huntington's disease (HD) patients and their genetically at risk offspring. Although affected individuals are usually characterized by gross involuntary muscle movements, alterations in minute muscle tremor were also found in our sample of ten HD patients. Irregularities in tremor patterns were intensified with increased time since onset of the disorder and in addition reflected the effects of drug therapy for those on medication. The use of accelerometer measurements of muscle tremor may therefore, prove to be useful in evaluating new medications for affected individuals. For high risk immediate family members currently there is no safe and reliable method to identify, prior to clinical onset, any among them who will develop HD. Aberrant muscle tremor patterns resembling that shown by HD patients were found in one-third of a sample of 15 genetically at risk offspring. In the event an effective method of treatment is developed, early recognition of HD gene carriers by accelerometer tremor measurement could result in control of the disorder prior to substantial neurological damage."} {"id": "PMID:159081", "title": "[Kinetic differences in induction of the killers and producers of the macrophage migration inhibitory factor (MIF) in primary and secondary mixed murine leukocyte culture test].", "content": "Conditions are selected for the killer induction during primary and secondary responses in the one-way MLC, stimulated by x-irradiated or killed allogenic lymphocytes. MIF is found in the MLC culture medium as a sharp peak on the 2nd or the 3rd day of the primary reaction, or as a plato from the 1st day of the secondary reaction. In contrast, the killers are shown to be induced much later reaching their maximum on the 5th and the 4th days, respectively. If heated, instead of irradiated, allogenic lymphocytes were used for stimulation of the primary MLC reaction, the MIF-producer kinetics was not changed, but the killer induction was found to be delayed.", "contents": "[Kinetic differences in induction of the killers and producers of the macrophage migration inhibitory factor (MIF) in primary and secondary mixed murine leukocyte culture test]. Conditions are selected for the killer induction during primary and secondary responses in the one-way MLC, stimulated by x-irradiated or killed allogenic lymphocytes. MIF is found in the MLC culture medium as a sharp peak on the 2nd or the 3rd day of the primary reaction, or as a plato from the 1st day of the secondary reaction. In contrast, the killers are shown to be induced much later reaching their maximum on the 5th and the 4th days, respectively. If heated, instead of irradiated, allogenic lymphocytes were used for stimulation of the primary MLC reaction, the MIF-producer kinetics was not changed, but the killer induction was found to be delayed."} {"id": "PMID:159082", "title": "[Blood serum as a factor of chromatin condensation in trisomy-21 (Down's syndrome)].", "content": "The influence of blood sera from patients with Down's syndrome and healthy ones, and different serum fractions on the structure of the deoxyribonucleoprotein systems (DNP-system) has been studied. It was demonstrated that non-fractionated sera of the patients produce a condensation effect on the DNP-system in contradistinction to the sera from healthy people. The analysis of the action of single serum fractions showed that different condensation effect results from the activity of high molecular nondialysable thermosensitive components whose action disappears at gel-filtration of serum proteins. A possibility of the humoral control over chromatin structural organization in vivo is discussed in terms of the evidence on the similarity of serum proteins and chromosomal nonhistone proteins.", "contents": "[Blood serum as a factor of chromatin condensation in trisomy-21 (Down's syndrome)]. The influence of blood sera from patients with Down's syndrome and healthy ones, and different serum fractions on the structure of the deoxyribonucleoprotein systems (DNP-system) has been studied. It was demonstrated that non-fractionated sera of the patients produce a condensation effect on the DNP-system in contradistinction to the sera from healthy people. The analysis of the action of single serum fractions showed that different condensation effect results from the activity of high molecular nondialysable thermosensitive components whose action disappears at gel-filtration of serum proteins. A possibility of the humoral control over chromatin structural organization in vivo is discussed in terms of the evidence on the similarity of serum proteins and chromosomal nonhistone proteins."} {"id": "PMID:159083", "title": "[Structural changes in the rat myocardium in the process of adaptation to high-altitude hypoxia].", "content": "Changes in the weight of diverse parts of the heart, in cross-sectional area of myocytes and vascularization of the myocardium were studied in rat experiments under altitude hypoxia (3200 m above the sea level) during adaptation of the animals to hypoxia. Morphologically, the compensatory and adaptive reactions of the rat to hypoxia were shown by its increases weight at the expense of hypertrophy of the right ventricular myocardium. Vascularization of the myocardium augmented synchronously to its growing hypertrophy.", "contents": "[Structural changes in the rat myocardium in the process of adaptation to high-altitude hypoxia]. Changes in the weight of diverse parts of the heart, in cross-sectional area of myocytes and vascularization of the myocardium were studied in rat experiments under altitude hypoxia (3200 m above the sea level) during adaptation of the animals to hypoxia. Morphologically, the compensatory and adaptive reactions of the rat to hypoxia were shown by its increases weight at the expense of hypertrophy of the right ventricular myocardium. Vascularization of the myocardium augmented synchronously to its growing hypertrophy."} {"id": "PMID:159084", "title": "Tissue-specific inhibitor of lymphocyte proliferation extracted and purified from calf spleen. Biological and chemical properties.", "content": "A partly purified calf spleen extract which inhibits lymphocyte proliferation in a tissue-specific, species-nonspecific, nontoxic, and reversible way, and may thus contain a chalone-like activity, has been further characterized. Our results show that the inhibitor works in G1-phase. The activity is resistant to heat, trypsin- and ribonuclease-treatment. It appears to be an acidic molecule and it does not appear to contain ribonucleic acid. These properties are compared to the characteristics which have been described for tissue-specific inhibitors of lymphocyte proliferation by other authors.", "contents": "Tissue-specific inhibitor of lymphocyte proliferation extracted and purified from calf spleen. Biological and chemical properties. A partly purified calf spleen extract which inhibits lymphocyte proliferation in a tissue-specific, species-nonspecific, nontoxic, and reversible way, and may thus contain a chalone-like activity, has been further characterized. Our results show that the inhibitor works in G1-phase. The activity is resistant to heat, trypsin- and ribonuclease-treatment. It appears to be an acidic molecule and it does not appear to contain ribonucleic acid. These properties are compared to the characteristics which have been described for tissue-specific inhibitors of lymphocyte proliferation by other authors."} {"id": "PMID:159092", "title": "[Effect of diphenylhydantoin administered during gestation and lactation on the motor development and cerebellar histology of the young rat].", "content": "Rattus norvegicus females were treated by diphenylhydantoin (D.P.H.), all along pregnancy and lactation. 4 groups were constituted: a 100 mg DPH/kg/day group, a 50 mg DPH/kg/day group; a placebo group (treated with pure water), and control group. D.P.H. was given twice a day by a gastric tube. The cerebellar Purkinje cells studied through light microscopy and transmission electron microscopy in young rats (25 days old) showed no visible alteration. 2 motorcoordination tests were applied to the young rats, during their 2nd and 3rd weeks of post-natal life. Young rats of DPH 100, DPH 50 and placebo groups showed a backwardness relatively to control. This backwardness may be attributed to the maternal forced feeding stress, but not to a specific action of the DPH.", "contents": "[Effect of diphenylhydantoin administered during gestation and lactation on the motor development and cerebellar histology of the young rat]. Rattus norvegicus females were treated by diphenylhydantoin (D.P.H.), all along pregnancy and lactation. 4 groups were constituted: a 100 mg DPH/kg/day group, a 50 mg DPH/kg/day group; a placebo group (treated with pure water), and control group. D.P.H. was given twice a day by a gastric tube. The cerebellar Purkinje cells studied through light microscopy and transmission electron microscopy in young rats (25 days old) showed no visible alteration. 2 motorcoordination tests were applied to the young rats, during their 2nd and 3rd weeks of post-natal life. Young rats of DPH 100, DPH 50 and placebo groups showed a backwardness relatively to control. This backwardness may be attributed to the maternal forced feeding stress, but not to a specific action of the DPH."} {"id": "PMID:159093", "title": "[Demonstration of multiple innervation of skeletal muscle fibers in the rat following localized repetitive freezing of the sciatic nerve].", "content": "The medial head of the gastrocnemius muscle of the rat was denervated by three successive freezings of the sciatic nerve at the same focal localization. After the third denervation, the compound potentials obtained during a transient period of time indicated that some muscle fibres are innervated by two or several axonal terminals. It can be concluded from the electrophysiological, histological and cytoenzymological results that this multiple innervation is polyneural and located within a single end-plate.", "contents": "[Demonstration of multiple innervation of skeletal muscle fibers in the rat following localized repetitive freezing of the sciatic nerve]. The medial head of the gastrocnemius muscle of the rat was denervated by three successive freezings of the sciatic nerve at the same focal localization. After the third denervation, the compound potentials obtained during a transient period of time indicated that some muscle fibres are innervated by two or several axonal terminals. It can be concluded from the electrophysiological, histological and cytoenzymological results that this multiple innervation is polyneural and located within a single end-plate."} {"id": "PMID:159094", "title": "[Molecular forms of acetylcholinesterase in the slow muscle and the fast muscle of the chicken].", "content": "Five molecular forms of AChE are present in the slow (ALD) and twitch (PLD) muscles of the chick. These forms have 4 S, 7 S, 11 S, 15 S and 20 S sedimentation coefficient in sucrose gradient. The heaviest forms, the 20 S and 15 S of AChE are absent in uninnervated muscles and present in innervated muscles. In innervated muscles, the 20 S and 15 S AChE are present in both nerve-free segments and end-plates zones. The 20 S and 15 S which are not specifically associated with the end-plate zones in the chick could be considered as a biochemical \"marker\" of neuromuscular interactions.", "contents": "[Molecular forms of acetylcholinesterase in the slow muscle and the fast muscle of the chicken]. Five molecular forms of AChE are present in the slow (ALD) and twitch (PLD) muscles of the chick. These forms have 4 S, 7 S, 11 S, 15 S and 20 S sedimentation coefficient in sucrose gradient. The heaviest forms, the 20 S and 15 S of AChE are absent in uninnervated muscles and present in innervated muscles. In innervated muscles, the 20 S and 15 S AChE are present in both nerve-free segments and end-plates zones. The 20 S and 15 S which are not specifically associated with the end-plate zones in the chick could be considered as a biochemical \"marker\" of neuromuscular interactions."} {"id": "PMID:159095", "title": "[In vitro expression of the thyroid gland genome. Difference between chromatin and DNA].", "content": "In vitro, transcription by thyroid chromatin has been compared to that carried out by deproteinized DNA prepared from the same tissue. The chromatin-primed transcripts are represented by 4S and 10S RNAs, whereas the DNA-primed transcript is heterogenous and polydisperse. The sequences expressed in vitro have been analyzed by hydridization of 4S and 10S RNA to the total native thyroid DNA. Most of the sequences transcribed are represented by intermediate repetitive-associated an unique sequence. Furthermore, they are expressed only by chromatin and not by DNA. Thus, thyroid chromatin very likely holds in vitro the same fonctional restriction exhibited in vivo, whereas the transcriptional behaviour of thyroid DNA is totally aspecific.", "contents": "[In vitro expression of the thyroid gland genome. Difference between chromatin and DNA]. In vitro, transcription by thyroid chromatin has been compared to that carried out by deproteinized DNA prepared from the same tissue. The chromatin-primed transcripts are represented by 4S and 10S RNAs, whereas the DNA-primed transcript is heterogenous and polydisperse. The sequences expressed in vitro have been analyzed by hydridization of 4S and 10S RNA to the total native thyroid DNA. Most of the sequences transcribed are represented by intermediate repetitive-associated an unique sequence. Furthermore, they are expressed only by chromatin and not by DNA. Thus, thyroid chromatin very likely holds in vitro the same fonctional restriction exhibited in vivo, whereas the transcriptional behaviour of thyroid DNA is totally aspecific."} {"id": "PMID:159096", "title": "[Effect of glycolysis inhibitors on the uptake of metronidazole by the protozoa Tritrichomonas foetus and Entamoeba invadens].", "content": "Uptake of metronidazole by the anaerobic protozoa, Tritichomonas foetus and Entamoeba invadens is dependent on the energy metabolism of these organisms. The inhibitors of glycolysis, iodoacetamide and sodium fluoride, inhibit the uptake. An atmosphere of hydrogen eliminates this inhibition in the hydrogenase-containing T. foetus but not in E. invadens which lacks the enzyme.", "contents": "[Effect of glycolysis inhibitors on the uptake of metronidazole by the protozoa Tritrichomonas foetus and Entamoeba invadens]. Uptake of metronidazole by the anaerobic protozoa, Tritichomonas foetus and Entamoeba invadens is dependent on the energy metabolism of these organisms. The inhibitors of glycolysis, iodoacetamide and sodium fluoride, inhibit the uptake. An atmosphere of hydrogen eliminates this inhibition in the hydrogenase-containing T. foetus but not in E. invadens which lacks the enzyme."} {"id": "PMID:159097", "title": "[Effect of urethane on the granulopexic activity of the reticuloendothelial system and the production of virus inhibiting factor or interferon].", "content": "Urethane (ethyl carbamate) did not affect the rate of the clearance of carbon from the blood in splenectomized mice, while this compound slowed down the carbon clearance in intact mice. Production of virus-inhibiting factor (IF) or interferon, especially early IF induced by virus was impaired by urethane in splenctomized mice as well as intact ones. The role of reticulo-endothelial system in IF formation was discussed.", "contents": "[Effect of urethane on the granulopexic activity of the reticuloendothelial system and the production of virus inhibiting factor or interferon]. Urethane (ethyl carbamate) did not affect the rate of the clearance of carbon from the blood in splenectomized mice, while this compound slowed down the carbon clearance in intact mice. Production of virus-inhibiting factor (IF) or interferon, especially early IF induced by virus was impaired by urethane in splenctomized mice as well as intact ones. The role of reticulo-endothelial system in IF formation was discussed."} {"id": "PMID:159098", "title": "[Effect of long-term phenytoin treatment on the levels of calcium and magnesium in rat femurs].", "content": "In young male rats, long-term treatment with phenyto\u00efn reduces the amount of calcium and magnesium in the femurs and provokes a stimulation of the parathyroi\u00efds witnessed by the hypertrophy and hyperplasy of the parathyroid cells. Neither plasma calcium nor plasma and erythrocyte magnesium are modified.", "contents": "[Effect of long-term phenytoin treatment on the levels of calcium and magnesium in rat femurs]. In young male rats, long-term treatment with phenyto\u00efn reduces the amount of calcium and magnesium in the femurs and provokes a stimulation of the parathyroi\u00efds witnessed by the hypertrophy and hyperplasy of the parathyroid cells. Neither plasma calcium nor plasma and erythrocyte magnesium are modified."} {"id": "PMID:159099", "title": "[Histo-autoradiographic study of a testosterone target organ, the epididymis of the lizard (Lacerta vivipara), after administration of 3H-17 beta-estradiol].", "content": "[6,7 3H] oestradiol-17 beta was injected into castrated male viviparous lizards in order to compare retention of this steroid to that of testosterone during the period of sexual activity. Retention of the isotope in epididymis was greater than in blood, lung and stomach. Radioautographs of epididymis indicated that oestradiol or a metabolite was concentrated in cell nuclei and over discharged secretory granules as was observed with testosterone. Reason of such binding is not yet known.", "contents": "[Histo-autoradiographic study of a testosterone target organ, the epididymis of the lizard (Lacerta vivipara), after administration of 3H-17 beta-estradiol]. [6,7 3H] oestradiol-17 beta was injected into castrated male viviparous lizards in order to compare retention of this steroid to that of testosterone during the period of sexual activity. Retention of the isotope in epididymis was greater than in blood, lung and stomach. Radioautographs of epididymis indicated that oestradiol or a metabolite was concentrated in cell nuclei and over discharged secretory granules as was observed with testosterone. Reason of such binding is not yet known."} {"id": "PMID:159100", "title": "[Effect of various 2-methyl-(4'-chlorobenzoyl)-4-phenoxy)-2 propionic acid (LF 153) analogs on the respiratory activity of rat liver mitochondria].", "content": "Seven analogs of methyl-2 [chloro-4' benzoyl)-4 phenoxy]-2 propionic acid, (LF 153) have been tested for their effects on respiration and phosphorylation of rat liver mitochondria suspensions. They differ from one another by the sort of binding between both aromatic cycle as well as by the nature and position of the halogenated substitutions and alpha methylation in the propionic chain. All the compounds which have been tested acted as inhibitors of the electron transport chain and uncouplers of phosphorylations.", "contents": "[Effect of various 2-methyl-(4'-chlorobenzoyl)-4-phenoxy)-2 propionic acid (LF 153) analogs on the respiratory activity of rat liver mitochondria]. Seven analogs of methyl-2 [chloro-4' benzoyl)-4 phenoxy]-2 propionic acid, (LF 153) have been tested for their effects on respiration and phosphorylation of rat liver mitochondria suspensions. They differ from one another by the sort of binding between both aromatic cycle as well as by the nature and position of the halogenated substitutions and alpha methylation in the propionic chain. All the compounds which have been tested acted as inhibitors of the electron transport chain and uncouplers of phosphorylations."} {"id": "PMID:159101", "title": "[Kinetics of Mn2+ ion metabolism in rat hepatic tissue].", "content": "Intravenous injection of MnSO4 with 54Mn (0,33 mg/100 g) into rats showed that Mn2+ ions are transferred into intracellular organites and specially into mitochondria. The mitochondrial clearance curve of 54Mn has been analyzed. It is appeared that three compartments participate in the distribution of Mn2+. The third compartment is the most important.", "contents": "[Kinetics of Mn2+ ion metabolism in rat hepatic tissue]. Intravenous injection of MnSO4 with 54Mn (0,33 mg/100 g) into rats showed that Mn2+ ions are transferred into intracellular organites and specially into mitochondria. The mitochondrial clearance curve of 54Mn has been analyzed. It is appeared that three compartments participate in the distribution of Mn2+. The third compartment is the most important."} {"id": "PMID:159102", "title": "[Intestinal and renal excretion of phosphorus and calcium in rats receiving potassium metabisulfite, tannic acid and ethanol, alone or in combination].", "content": "In the young rat, the addition of potassium metabisulfite or tannic acid in the diet decreases the fecal excretion of phosphorus, but increases its urinary excretion, whereas the addition of ethanol induces opposite results. These different effects are additive. On the other hand, the ethanol increases the urinary excretion of calcium, but only in the animals which receive neither metabisulfite nor tannic acid.", "contents": "[Intestinal and renal excretion of phosphorus and calcium in rats receiving potassium metabisulfite, tannic acid and ethanol, alone or in combination]. In the young rat, the addition of potassium metabisulfite or tannic acid in the diet decreases the fecal excretion of phosphorus, but increases its urinary excretion, whereas the addition of ethanol induces opposite results. These different effects are additive. On the other hand, the ethanol increases the urinary excretion of calcium, but only in the animals which receive neither metabisulfite nor tannic acid."} {"id": "PMID:159104", "title": "[Lactate dehydrogenase and its isoenzymes in human umbilical cord tissue].", "content": "Study on umbilical cord tissue, completely bloodless, for determination of lactate deshydrogenase activity and its distribution among the five iso-enzymes. Comparison with placenta, amniotic fluid, serums of blood of cord and of mother. Cord tissue is very active (about 360 muKatals, in average) and it is a similar result in placenta (as it is possibly bloodless). Blood serum of cord is more active than amniotic fluid, which is more active than maternal serum, but they are 80 to 200 times less active than cord tissue. After electrophoresis, a very large predominance of the slow iso-enzymes L.D.H. 4--5 is found in cord tissue (72%), amniotic fluid (67%) and placenta (56%), whereas the fast iso-enzymes L.D.H. 1--2 are predominant in the serums of cord blood and of mother. These data indicate an intense metabolic activity in the cord tissue, which has also an high level of lactate, and this seems related to the foetal metabolism for anaerobic glycolysis in oxygen weakly provided tissues.", "contents": "[Lactate dehydrogenase and its isoenzymes in human umbilical cord tissue]. Study on umbilical cord tissue, completely bloodless, for determination of lactate deshydrogenase activity and its distribution among the five iso-enzymes. Comparison with placenta, amniotic fluid, serums of blood of cord and of mother. Cord tissue is very active (about 360 muKatals, in average) and it is a similar result in placenta (as it is possibly bloodless). Blood serum of cord is more active than amniotic fluid, which is more active than maternal serum, but they are 80 to 200 times less active than cord tissue. After electrophoresis, a very large predominance of the slow iso-enzymes L.D.H. 4--5 is found in cord tissue (72%), amniotic fluid (67%) and placenta (56%), whereas the fast iso-enzymes L.D.H. 1--2 are predominant in the serums of cord blood and of mother. These data indicate an intense metabolic activity in the cord tissue, which has also an high level of lactate, and this seems related to the foetal metabolism for anaerobic glycolysis in oxygen weakly provided tissues."} {"id": "PMID:159105", "title": "[Histological study of the development of Fasciola hepatics in Lymnaea truncatula, L. glabra and L. palustris infested at hatching].", "content": "The development of Fasciola hepatica is histologically analysed in Limnaea truncatula, L. glabra and L. palustris infested at hatching with a single miracidium. The development of the redial generations of Fasciola is not affected by the species of snail host but depends on growth of the snail. In snails of size within 2 mm (considered at the day 49 of infestation to 20 degrees C), the rediae show a delay of maturity compared with rediae observed in snails of higher sizes. The distribution of redia 1 of generation 1 should have an influence on growth of the snail host.", "contents": "[Histological study of the development of Fasciola hepatics in Lymnaea truncatula, L. glabra and L. palustris infested at hatching]. The development of Fasciola hepatica is histologically analysed in Limnaea truncatula, L. glabra and L. palustris infested at hatching with a single miracidium. The development of the redial generations of Fasciola is not affected by the species of snail host but depends on growth of the snail. In snails of size within 2 mm (considered at the day 49 of infestation to 20 degrees C), the rediae show a delay of maturity compared with rediae observed in snails of higher sizes. The distribution of redia 1 of generation 1 should have an influence on growth of the snail host."} {"id": "PMID:159106", "title": "[Hormonal regulation of 5 alpha-reductase activity in anterior pituitary gland microsomes of the male rat].", "content": "It was previously shown that the microsomal 5 alpha-reductase activity in the male rat pituitary was increased by castration. Subcutaneous administration of androgens to castrated rats prevented the rise in 5 alpha-reductase activity. Their relative efficiency was as follows: 5 alpha-dihydrotestosterone greater than 5 alpha-androstane-3 alpha, 17 beta-diol greater than testosterone. Under our experimental conditions 5 alpha-androstane-3 beta, 17 beta-diol and estrogens were inefficient. The rise in 5 alpha-reductase activity following castration is exclusively located in hypophysis and it is probably due to an increased of the enzyme biosynthesis.", "contents": "[Hormonal regulation of 5 alpha-reductase activity in anterior pituitary gland microsomes of the male rat]. It was previously shown that the microsomal 5 alpha-reductase activity in the male rat pituitary was increased by castration. Subcutaneous administration of androgens to castrated rats prevented the rise in 5 alpha-reductase activity. Their relative efficiency was as follows: 5 alpha-dihydrotestosterone greater than 5 alpha-androstane-3 alpha, 17 beta-diol greater than testosterone. Under our experimental conditions 5 alpha-androstane-3 beta, 17 beta-diol and estrogens were inefficient. The rise in 5 alpha-reductase activity following castration is exclusively located in hypophysis and it is probably due to an increased of the enzyme biosynthesis."} {"id": "PMID:159107", "title": "[Effect of L-eburnamonine on bronchial respiratory resistance in the anesthetized guinea pig. Comparison with vincamine].", "content": "In anesthetized guinea pigs, i.v. injection of l-eburnamonine (l-E) induced a moderate constriction of bronchia. This bronchoconstriction was partially antagonized by atropine and brompheniramine and nearly completely inhibited by papaverine; methysergide was devoid of antagonistic activity. It was suggested that the contractive activity of l-E is complex and not specific. Similar results were obtained with vincamine (Vi) but vincamine's bronchoconstriction was not completely inhibited by papaverine. Furthermore, the bronchoconstrictor activity of Vi was more important and more durable than that of l-E.", "contents": "[Effect of L-eburnamonine on bronchial respiratory resistance in the anesthetized guinea pig. Comparison with vincamine]. In anesthetized guinea pigs, i.v. injection of l-eburnamonine (l-E) induced a moderate constriction of bronchia. This bronchoconstriction was partially antagonized by atropine and brompheniramine and nearly completely inhibited by papaverine; methysergide was devoid of antagonistic activity. It was suggested that the contractive activity of l-E is complex and not specific. Similar results were obtained with vincamine (Vi) but vincamine's bronchoconstriction was not completely inhibited by papaverine. Furthermore, the bronchoconstrictor activity of Vi was more important and more durable than that of l-E."} {"id": "PMID:159109", "title": "[Intestinal motility after intraduodenal and intrajejunal feeding].", "content": "Post-prandial intestinal motility, analysed through two electromyographic parameters, duration of inhibition of myoelectric complex (DIMC) and percentage of spike potentials (PSP), was studied after ingestion of glucids, proteins and lipids. Post-prandial intestinal motility depends on both chemical nature and caloric load of nutriments: DICM depends on those two factors but PSP only depends on nature of nutriments. Post-prandial intestinal motility also depends on route of administration of nutriments. Intra-jejunal administration versus intra-duodenal administration increases DIMC observed for glucids and proteins, diminishes DIMC observed for lipids and diminishes PSP observed for glucids and proteins. These results indicate a specificity of intestinal post-prandial motility with characteristics of nutriments. Intestinal digestion and absorption of nutriments, just as hormonal secretion in response to intestinal passage of nutriments could explain such a specificity.", "contents": "[Intestinal motility after intraduodenal and intrajejunal feeding]. Post-prandial intestinal motility, analysed through two electromyographic parameters, duration of inhibition of myoelectric complex (DIMC) and percentage of spike potentials (PSP), was studied after ingestion of glucids, proteins and lipids. Post-prandial intestinal motility depends on both chemical nature and caloric load of nutriments: DICM depends on those two factors but PSP only depends on nature of nutriments. Post-prandial intestinal motility also depends on route of administration of nutriments. Intra-jejunal administration versus intra-duodenal administration increases DIMC observed for glucids and proteins, diminishes DIMC observed for lipids and diminishes PSP observed for glucids and proteins. These results indicate a specificity of intestinal post-prandial motility with characteristics of nutriments. Intestinal digestion and absorption of nutriments, just as hormonal secretion in response to intestinal passage of nutriments could explain such a specificity."} {"id": "PMID:159110", "title": "[Effect of protein deprivation on ammonia metabolism in the rat].", "content": "In order to investigate the mechanisms of the hyperammonemia previously described in protein deprivation, the effects of sucrose and fasting on the ammonia metabolism were studied in control, streptozotocine-induced diabetics and colectomized rats. Hyperammonemia, hyperglutaminemia, hypouremia and intolerance to an ammonium load were observed in the control group after a 5 days sucrose-feeding. Any of these abnormalities were found in the diabetic animals whereas hyperglutaminemia did not occur in colectomized animals. It is concluded that protein deprivation obtained by sucrose feeding involves an hyperammonemia by a reduction of ureogenesis (which seemed to be related to an elevation of the ratio insulin/glucagon) and an hyperglutamininemia of colic origin.", "contents": "[Effect of protein deprivation on ammonia metabolism in the rat]. In order to investigate the mechanisms of the hyperammonemia previously described in protein deprivation, the effects of sucrose and fasting on the ammonia metabolism were studied in control, streptozotocine-induced diabetics and colectomized rats. Hyperammonemia, hyperglutaminemia, hypouremia and intolerance to an ammonium load were observed in the control group after a 5 days sucrose-feeding. Any of these abnormalities were found in the diabetic animals whereas hyperglutaminemia did not occur in colectomized animals. It is concluded that protein deprivation obtained by sucrose feeding involves an hyperammonemia by a reduction of ureogenesis (which seemed to be related to an elevation of the ratio insulin/glucagon) and an hyperglutamininemia of colic origin."} {"id": "PMID:159111", "title": "[A and C particles in mouse embryos].", "content": "Electron microscopic examination of embryos of the BALB/c and AKR strains of mice from the 1-cell stage to 14 days of age revealed 2 types of intracisternal A particles, one type of C particle budding into the extracellular space and an endoplasmic reticulum-association \"dense-cored veiscle\". The occurrence of the particles showed a marked dependence on the developmental stage of the embryo. A small percentage of 1 blastomere embryos in both strains showed the presence of a small number of A particles. Embryos of 1 to 16 blastomeres of the AKR strain with A particles were on average more frequent than in the BALB/c strain. The percentage of 7 and 14 day embryos with C particles was much greater in AKR than in Balb/c mice.", "contents": "[A and C particles in mouse embryos]. Electron microscopic examination of embryos of the BALB/c and AKR strains of mice from the 1-cell stage to 14 days of age revealed 2 types of intracisternal A particles, one type of C particle budding into the extracellular space and an endoplasmic reticulum-association \"dense-cored veiscle\". The occurrence of the particles showed a marked dependence on the developmental stage of the embryo. A small percentage of 1 blastomere embryos in both strains showed the presence of a small number of A particles. Embryos of 1 to 16 blastomeres of the AKR strain with A particles were on average more frequent than in the BALB/c strain. The percentage of 7 and 14 day embryos with C particles was much greater in AKR than in Balb/c mice."} {"id": "PMID:159112", "title": "[Cytological and cytochemical effects of a liver extract from an adult rat on chick embryo hepatocytes and fibroblasts cultivated in vitro].", "content": "The effects of an extract from adult liver on chick embryo hepatocytes and fibroblasts cultivated in vitro are studied with cytological and quantitative cytochemical methods. This substance inhibits the multiplication of hepatocytes adn prevents these cells from entering into the S phase of the cycle. No effect is observed on the chick embryo fibroblasts. Not any morphological alterations are observed in the two cell types.", "contents": "[Cytological and cytochemical effects of a liver extract from an adult rat on chick embryo hepatocytes and fibroblasts cultivated in vitro]. The effects of an extract from adult liver on chick embryo hepatocytes and fibroblasts cultivated in vitro are studied with cytological and quantitative cytochemical methods. This substance inhibits the multiplication of hepatocytes adn prevents these cells from entering into the S phase of the cycle. No effect is observed on the chick embryo fibroblasts. Not any morphological alterations are observed in the two cell types."} {"id": "PMID:159114", "title": "[Arachidonic acid activation of the rat cardiovascular system].", "content": "The hypotensive activity of arachidonic acid is more important by intraaortic than by intravenous injection, in the rat. The evisceration of the animal abolishes this difference and reduces the activity of arachidonic acid. This action is not accompanied by thrombopenia and is only observed with high doses of arachidonic acid in this species. The hypotensive activity is inhibited by indomethacin but not by tranylcypromine.", "contents": "[Arachidonic acid activation of the rat cardiovascular system]. The hypotensive activity of arachidonic acid is more important by intraaortic than by intravenous injection, in the rat. The evisceration of the animal abolishes this difference and reduces the activity of arachidonic acid. This action is not accompanied by thrombopenia and is only observed with high doses of arachidonic acid in this species. The hypotensive activity is inhibited by indomethacin but not by tranylcypromine."} {"id": "PMID:159115", "title": "Treatment of unilateral iliac artery disease by femorofemoral bypass grafting.", "content": "Between Jan. 1, 1970 and June 30, 1977, 50 men and 23 women underwent femorofemoral bypass grafting. The average age of the group was 64.7 years. The procedure was performed for disabling claudication in 50 patients and for limb threatening ischemia in 23. Knitted Dacron grafts were used in all but two patients. The operative mortality was 4.1% and the late mortality 21.9%. There were six complications related to the prostheses, three infected grafts and three false aneurysms. Thrombosis of the graft occurred in 15 patients; the graft was successfully revised in 2. The cumulative 5-year patency rate determined by life-table methods was 73.4%. The causes of failure appeared to be well defined and unilateral iliac artery disease. The donor iliac artery, poor runoff through a diseases deep femoral artery on the recipient side and infection of the graft. This study indicates that femoro-femoral bypass has a definite place in the management of patients with unilateral iliac artery disease. The procedure can be performed on selected patients with a low operative mortality and an acceptable patency rate.", "contents": "Treatment of unilateral iliac artery disease by femorofemoral bypass grafting. Between Jan. 1, 1970 and June 30, 1977, 50 men and 23 women underwent femorofemoral bypass grafting. The average age of the group was 64.7 years. The procedure was performed for disabling claudication in 50 patients and for limb threatening ischemia in 23. Knitted Dacron grafts were used in all but two patients. The operative mortality was 4.1% and the late mortality 21.9%. There were six complications related to the prostheses, three infected grafts and three false aneurysms. Thrombosis of the graft occurred in 15 patients; the graft was successfully revised in 2. The cumulative 5-year patency rate determined by life-table methods was 73.4%. The causes of failure appeared to be well defined and unilateral iliac artery disease. The donor iliac artery, poor runoff through a diseases deep femoral artery on the recipient side and infection of the graft. This study indicates that femoro-femoral bypass has a definite place in the management of patients with unilateral iliac artery disease. The procedure can be performed on selected patients with a low operative mortality and an acceptable patency rate."} {"id": "PMID:159116", "title": "Knitted Dacron ultra-lightweight grafts--a warning.", "content": "A 61-year-old man presented with gross femoral and abdominal pulsation secondary to severe ectasia of an ultra-lightweight Dacron graft. All patients who have received this particular graft should be followed up closely and probably the graft should be replaced if progressive enlargement occurs.", "contents": "Knitted Dacron ultra-lightweight grafts--a warning. A 61-year-old man presented with gross femoral and abdominal pulsation secondary to severe ectasia of an ultra-lightweight Dacron graft. All patients who have received this particular graft should be followed up closely and probably the graft should be replaced if progressive enlargement occurs."} {"id": "PMID:159119", "title": "Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions.", "content": "Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy.", "contents": "Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions. Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy."} {"id": "PMID:159118", "title": "A rational approach to dementia.", "content": "Dementia is a common problem facing all medical practitioners and it frequently results in hospitalization and death. This review provides a framework for dealing with dementia in clinical practice that is based on both traditional concepts and recent advances in the understanding of the problem. Distinguishing at the bedside between dementia and other disorders of intellect is emphasized. The main causes of dementia and their clinical characteristics are reviewed and a rational approach to definitive diagnosis is developed. Simple, effective symptomatic forms of therapy are described.", "contents": "A rational approach to dementia. Dementia is a common problem facing all medical practitioners and it frequently results in hospitalization and death. This review provides a framework for dealing with dementia in clinical practice that is based on both traditional concepts and recent advances in the understanding of the problem. Distinguishing at the bedside between dementia and other disorders of intellect is emphasized. The main causes of dementia and their clinical characteristics are reviewed and a rational approach to definitive diagnosis is developed. Simple, effective symptomatic forms of therapy are described."} {"id": "PMID:159120", "title": "Studies of mixed lymphocyte reactions, surface B cell antigens, and intracytoplasmic immunoglobulins in \"null cell\" acute lymphocytic leukemia.", "content": "Lymphoblasts from \"null cell\" acute lymphocytic leukemia (ALL) were analyzed for the pattern of proliferation displayed in a mixed lymphocyte reaction (MLR), the presence of a B cell surface antigen, and for the presence of intracytoplasmic immunoglobulin (ICIg). \"Null cell\" ALL was defined by cytologic and cytochemical criteria and by the absence of spontaneous rosette formation and surface membrane immunoglobulin in cell suspensions of the malignant lymphocytes. In eleven of fourteen patients the proliferative characteristics of lymphoblasts in the MLR were similar to those observed with normal B enriched lymphocytes. In eleven cases studied, anti-B cell serum reacted with a majority of the lymphoblasts. None of the ten cases examined displayed ICIg in the lymphoblasts. We conclude that the \"null\" lymphoblast from most cases of ALL is a B cell in an early stage of development.", "contents": "Studies of mixed lymphocyte reactions, surface B cell antigens, and intracytoplasmic immunoglobulins in \"null cell\" acute lymphocytic leukemia. Lymphoblasts from \"null cell\" acute lymphocytic leukemia (ALL) were analyzed for the pattern of proliferation displayed in a mixed lymphocyte reaction (MLR), the presence of a B cell surface antigen, and for the presence of intracytoplasmic immunoglobulin (ICIg). \"Null cell\" ALL was defined by cytologic and cytochemical criteria and by the absence of spontaneous rosette formation and surface membrane immunoglobulin in cell suspensions of the malignant lymphocytes. In eleven of fourteen patients the proliferative characteristics of lymphoblasts in the MLR were similar to those observed with normal B enriched lymphocytes. In eleven cases studied, anti-B cell serum reacted with a majority of the lymphoblasts. None of the ten cases examined displayed ICIg in the lymphoblasts. We conclude that the \"null\" lymphoblast from most cases of ALL is a B cell in an early stage of development."} {"id": "PMID:159121", "title": "T-cell chronic lymphocytic leukemia: report of a case and review of the literature.", "content": "We recently observed a unique case of T-cell type chronic lymphocytic leukemia, documented by cell surface marker analyses. Immunologic tests at the time of diagnosis were as follows: 1) skin tests were negative; 2) in vitro lymphocyte responses to antigens or pokeweed mitogen were absent; 3) in vitro lymphocyte responses to phytohemagglutinin, concanavalin-A or allogeneic cells were low but significant; and 4) stimulating capacity of leukemic T cells were absent. Chromosomal analysis of bone marrow showed a pattern of 45 chromosomes with a marker chromosome. Terminal deoxynucleotidyl transferase activity was very low. Patient responded extremely well to COP (cyclophosphamide-oncovin-prednisone) therapy. Patient died of recurrent transitional cell carcinoma while his leukemia was in complete remission, approximately 20 months after the diagnosis of T-cell CLL.", "contents": "T-cell chronic lymphocytic leukemia: report of a case and review of the literature. We recently observed a unique case of T-cell type chronic lymphocytic leukemia, documented by cell surface marker analyses. Immunologic tests at the time of diagnosis were as follows: 1) skin tests were negative; 2) in vitro lymphocyte responses to antigens or pokeweed mitogen were absent; 3) in vitro lymphocyte responses to phytohemagglutinin, concanavalin-A or allogeneic cells were low but significant; and 4) stimulating capacity of leukemic T cells were absent. Chromosomal analysis of bone marrow showed a pattern of 45 chromosomes with a marker chromosome. Terminal deoxynucleotidyl transferase activity was very low. Patient responded extremely well to COP (cyclophosphamide-oncovin-prednisone) therapy. Patient died of recurrent transitional cell carcinoma while his leukemia was in complete remission, approximately 20 months after the diagnosis of T-cell CLL."} {"id": "PMID:159124", "title": "Concanavalin A-inducible suppressor cells in regional lymph nodes of cancer patients.", "content": "Regional tumor-draining lymph nodes of 11 of 14 patients with urological tumors and one of four controls studied contained suppressor cell precursors that could be activated by concanavalin A (Con A) to suppress the proliferative response of autologous lymphocytes to Con A. In contrast, no suppression of lymphocyte proliferation by lymph node cells that were not activated with Con A was observed in four patients tested. The suppressive effect was not due to decreased viability or increased release of cold thymidine by Con A-activated cells nor to alteration in the time course of the proliferative response of Con A-activated cells. Mitomycin C treatment of lymph node cells 24 hr after activation did not abrogate their suppressive activity. Peak suppression was observed after 72 hr in culture. The amount of suppression measured could be maximized by treatment of suppressor cells with mitomycin C 24 hr after activation and by washing the cells immediately before pulse labeling with tritiated thymidine. The concentration of Con A required to produce peak suppression varied from patient to patient with optimal doses ranging from 5 to 25 microgram/ml.", "contents": "Concanavalin A-inducible suppressor cells in regional lymph nodes of cancer patients. Regional tumor-draining lymph nodes of 11 of 14 patients with urological tumors and one of four controls studied contained suppressor cell precursors that could be activated by concanavalin A (Con A) to suppress the proliferative response of autologous lymphocytes to Con A. In contrast, no suppression of lymphocyte proliferation by lymph node cells that were not activated with Con A was observed in four patients tested. The suppressive effect was not due to decreased viability or increased release of cold thymidine by Con A-activated cells nor to alteration in the time course of the proliferative response of Con A-activated cells. Mitomycin C treatment of lymph node cells 24 hr after activation did not abrogate their suppressive activity. Peak suppression was observed after 72 hr in culture. The amount of suppression measured could be maximized by treatment of suppressor cells with mitomycin C 24 hr after activation and by washing the cells immediately before pulse labeling with tritiated thymidine. The concentration of Con A required to produce peak suppression varied from patient to patient with optimal doses ranging from 5 to 25 microgram/ml."} {"id": "PMID:159130", "title": "Interaction of int protein with specific sites on lambda att DNA.", "content": "We have studied the interaction of highly purified Int protein with DNA restriction fragments from the lambda phage attachment site (attP) region. Two different DNA sequences are protected by bound Int protein against partial digestion by either pancreatic DNAase or neocarzinostatin. One Int binding site includes the 15 bp common core sequence (the crossover region for site-specific recombination) plus several bases of sequence adjoining the core in both the P and P' arms. The second Int-protected site occurs 70 bp to the right of the common core in the P' arm, just at the distal end of the sequence encoding Int protein. The two Int binding sites are of comparable size, 30-35 bp, but do not share any extensive sequence homology. The interaction of Int with the two sites is distinctly different, as defined by the observation that only the site in the P' arm and not the site at the common core region is protected by Int in the face of challenge by the polyanion heparin. Restriction fragments containing DNA from the bacterial attachment site (attB) region exhibit a different pattern of interaction with Int. In the absence of heparin, a smaller (15 bp) sequence, which includes the left half of the common core region and the common core-B arm juncture, is protected against nuclease digestion by Int protein. No sequences from this region are protected by Int in the presence of heparin.", "contents": "Interaction of int protein with specific sites on lambda att DNA. We have studied the interaction of highly purified Int protein with DNA restriction fragments from the lambda phage attachment site (attP) region. Two different DNA sequences are protected by bound Int protein against partial digestion by either pancreatic DNAase or neocarzinostatin. One Int binding site includes the 15 bp common core sequence (the crossover region for site-specific recombination) plus several bases of sequence adjoining the core in both the P and P' arms. The second Int-protected site occurs 70 bp to the right of the common core in the P' arm, just at the distal end of the sequence encoding Int protein. The two Int binding sites are of comparable size, 30-35 bp, but do not share any extensive sequence homology. The interaction of Int with the two sites is distinctly different, as defined by the observation that only the site in the P' arm and not the site at the common core region is protected by Int in the face of challenge by the polyanion heparin. Restriction fragments containing DNA from the bacterial attachment site (attB) region exhibit a different pattern of interaction with Int. In the absence of heparin, a smaller (15 bp) sequence, which includes the left half of the common core region and the common core-B arm juncture, is protected against nuclease digestion by Int protein. No sequences from this region are protected by Int in the presence of heparin."} {"id": "PMID:159127", "title": "Platinate toxicity: past, present, and prospects.", "content": "Using traditional toxicologic methods, four species were studied for their qualitative and quantitative predictiveness of the toxic effects of cis-dichlorodiammineplatinum(II) in man. Of the four species studied, mouse, monkey, rat, and dog, the latter two gave the best overall results. Using an in vivo rat model, it was found that except for chloroplatinic acid, eight of the tested analogs were less nephrotoxic than the parent drug, cis-dichlorodiammineplatinum(II). The in vitro renal toxicity screen using flounder tubules showed that of the 26 compounds studied, about half were less toxic than the parent compound. This in vitro mini-tox system can be performed about 30 times faster and at one fiftieth the cost of the in vivo model. The in vitro studies also provided evidence that the biochemical site of toxicity of platihates is on ATPases. The latter studies suggested a basis for unifying the mechanistic interpretation of the toxic actions on such disparate target organs as the kidney, nerve, stomach, and inner ear.", "contents": "Platinate toxicity: past, present, and prospects. Using traditional toxicologic methods, four species were studied for their qualitative and quantitative predictiveness of the toxic effects of cis-dichlorodiammineplatinum(II) in man. Of the four species studied, mouse, monkey, rat, and dog, the latter two gave the best overall results. Using an in vivo rat model, it was found that except for chloroplatinic acid, eight of the tested analogs were less nephrotoxic than the parent drug, cis-dichlorodiammineplatinum(II). The in vitro renal toxicity screen using flounder tubules showed that of the 26 compounds studied, about half were less toxic than the parent compound. This in vitro mini-tox system can be performed about 30 times faster and at one fiftieth the cost of the in vivo model. The in vitro studies also provided evidence that the biochemical site of toxicity of platihates is on ATPases. The latter studies suggested a basis for unifying the mechanistic interpretation of the toxic actions on such disparate target organs as the kidney, nerve, stomach, and inner ear."} {"id": "PMID:159138", "title": "[Demonstration of a soluble factor capable of inhibiting allogenic lymphocyte proliferation in man].", "content": "During the secondary mixed lymphocyte reaction (MLR), i.e. after the double in vitro allogenic sensitization between responding and stimulating cells bearing at least one HLA-DR incompatibility, suppressor cells are developed [1]. They are able to inhibit a primary MLR provided that the stimulating cells possess the same DR incompatibility as the immunizing cells. We report here that this inhibition is due to the production by these cells of a soluble suppressor factor which acts on responding cells provided that they share at least one gene product of the HLA-D region with the cells producing the factor. This a feedback process of auto-inhibition occurring after hyperimmunization. The action of this suppressor factor seems to be genetically restricted to an as yet unknown locus in linkage disequilibrium with HLA-DR.", "contents": "[Demonstration of a soluble factor capable of inhibiting allogenic lymphocyte proliferation in man]. During the secondary mixed lymphocyte reaction (MLR), i.e. after the double in vitro allogenic sensitization between responding and stimulating cells bearing at least one HLA-DR incompatibility, suppressor cells are developed [1]. They are able to inhibit a primary MLR provided that the stimulating cells possess the same DR incompatibility as the immunizing cells. We report here that this inhibition is due to the production by these cells of a soluble suppressor factor which acts on responding cells provided that they share at least one gene product of the HLA-D region with the cells producing the factor. This a feedback process of auto-inhibition occurring after hyperimmunization. The action of this suppressor factor seems to be genetically restricted to an as yet unknown locus in linkage disequilibrium with HLA-DR."} {"id": "PMID:159139", "title": "Visual problems in the handicapped child.", "content": "The importance of carrying out a preliminary examination of vision and eye movements in all handicapped is stressed. In any case of doubt a full ophthalmological and orthoptic examination is essential and is best carried out in the congenial environs of a District Handicap Centre. Eight hundred and ninety-three children with a wide variety of handicaps were seen at the Leeds Regional Child Assessment Centre between 1972 and 1977, and 324 were found to have a visual or visuomotor defect. The types of defects are discussed under headings which describe the main handicap.", "contents": "Visual problems in the handicapped child. The importance of carrying out a preliminary examination of vision and eye movements in all handicapped is stressed. In any case of doubt a full ophthalmological and orthoptic examination is essential and is best carried out in the congenial environs of a District Handicap Centre. Eight hundred and ninety-three children with a wide variety of handicaps were seen at the Leeds Regional Child Assessment Centre between 1972 and 1977, and 324 were found to have a visual or visuomotor defect. The types of defects are discussed under headings which describe the main handicap."} {"id": "PMID:159140", "title": "Assessing and facilitating play in handicapped children.", "content": "The importance of using the play period in an educational curriculum to promote social and cognitive growth is discussed, especially as it pertains to handicapped children. Facilitation and stimulation of play at the child's current level of functioning is advocated. A sample play programme is discussed as an illustration of how problems in planning can be handled. A list of decision points and important factors to consider in planning for play is then provided.", "contents": "Assessing and facilitating play in handicapped children. The importance of using the play period in an educational curriculum to promote social and cognitive growth is discussed, especially as it pertains to handicapped children. Facilitation and stimulation of play at the child's current level of functioning is advocated. A sample play programme is discussed as an illustration of how problems in planning can be handled. A list of decision points and important factors to consider in planning for play is then provided."} {"id": "PMID:159141", "title": "Profile: the voluntary council for handicapped children.", "content": "The Voluntary Council for Handicapped Children is an independently elected Council, established under the aegis of the National Children's Bureau in 1975. The Council arose from a recommendation in the Eileen Younghusband Working Party's report, Living with Handicap, in 1970. This major report draws attention to the gaps, overlaps and general lack of co-ordination and information about services for handicapped children. It recommended the creation of a genuinely multidisciplinary council to provide a forum for joint discussion and action, to offer a comprehensive advisory and information service covering all aspects of childhood disability. The Voluntary Council for Handicapped Children is unique in providing a comprehensive service for all categories of handicap, and for statutory and voluntary agencies. Parents and professionals can use the Council as a resource centre on an individual basis, although casework cannot be provided. The role of the Council is essentially that of a signpost to existing resources. It is, in effect, an advisory body collecting, evaluating and disseminating information, promoting study and discussion by organizations and individuals and seeking to identify gaps in present services.", "contents": "Profile: the voluntary council for handicapped children. The Voluntary Council for Handicapped Children is an independently elected Council, established under the aegis of the National Children's Bureau in 1975. The Council arose from a recommendation in the Eileen Younghusband Working Party's report, Living with Handicap, in 1970. This major report draws attention to the gaps, overlaps and general lack of co-ordination and information about services for handicapped children. It recommended the creation of a genuinely multidisciplinary council to provide a forum for joint discussion and action, to offer a comprehensive advisory and information service covering all aspects of childhood disability. The Voluntary Council for Handicapped Children is unique in providing a comprehensive service for all categories of handicap, and for statutory and voluntary agencies. Parents and professionals can use the Council as a resource centre on an individual basis, although casework cannot be provided. The role of the Council is essentially that of a signpost to existing resources. It is, in effect, an advisory body collecting, evaluating and disseminating information, promoting study and discussion by organizations and individuals and seeking to identify gaps in present services."} {"id": "PMID:159146", "title": "T cell-mediated immune responses of lupus-prone BXSB mice and other murine strains.", "content": "Cellular-mediated immunity in the newly described BXSB strain of mice, which is prone to autoimmune disease, has been compared with that of two other strains, C57Bl/6 and 129/J. Quantificaiton of cytotoxic T cell responses to alloantigens and viruses (lymphocytic choriomeningitis and vaccinia virus) showed no difference in the kinetics of appearance and relative activity of cytotoxic T cells per spleen between the young and old BXSB and the control mice. The T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all strains tested with respect to kinetics, but the size was greater by two-fold in C57Bl/6 mice. The susceptibility to systemic infection and subsequent induction of lymphocytes immune to Listeria monocytogenes were about equivalent in all strains. However, clearance of Listeria by the reticuloendothelial system and early non-immune bactericidal activity of the young and old BXSB were significantly lower than in the control strains. The results indicate that the cellular-mediated immunity (CMI) of BXSB mice compared favourably with that of other strains and that there is no apparent differences between CMI of BXSB mice before the onset of disease and during the course of disease. The role of the reduced reticuloendothelial function of BXSB mice in their autoimmune disease or in their high susceptibility to infection remains to be determined.", "contents": "T cell-mediated immune responses of lupus-prone BXSB mice and other murine strains. Cellular-mediated immunity in the newly described BXSB strain of mice, which is prone to autoimmune disease, has been compared with that of two other strains, C57Bl/6 and 129/J. Quantificaiton of cytotoxic T cell responses to alloantigens and viruses (lymphocytic choriomeningitis and vaccinia virus) showed no difference in the kinetics of appearance and relative activity of cytotoxic T cells per spleen between the young and old BXSB and the control mice. The T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all strains tested with respect to kinetics, but the size was greater by two-fold in C57Bl/6 mice. The susceptibility to systemic infection and subsequent induction of lymphocytes immune to Listeria monocytogenes were about equivalent in all strains. However, clearance of Listeria by the reticuloendothelial system and early non-immune bactericidal activity of the young and old BXSB were significantly lower than in the control strains. The results indicate that the cellular-mediated immunity (CMI) of BXSB mice compared favourably with that of other strains and that there is no apparent differences between CMI of BXSB mice before the onset of disease and during the course of disease. The role of the reduced reticuloendothelial function of BXSB mice in their autoimmune disease or in their high susceptibility to infection remains to be determined."} {"id": "PMID:159147", "title": "Depressed primary in vitro antibody response in rheumatoid arthritis.", "content": "We have studied the primary in vitro antibody response toward a hapten in cultures of peripheral blood lymphocytes from twenty-two patients suffering from regular rheumatoid arthritis (RA). These patients were not receiving immunosuppressive drugs or corticosteroids and had not taken Aspirin or non-steroidal anti-inflammatory agents for at least 72 hr. The control groups included thirty-two healthy subjects and twenty-seven control patients. The mean anti-TNP response of the RA patients was significantly lower than that of both control groups. No pre-existing anti-TNP or IgG response could be detected. A search for suppressor cells in co-cultures of RA and normal lymphocytes was negative. On the contrary, the extent of allogeneic enhancement in such co-cultures was comparable to that observed when control lymphocytes were co-cultured. RA serum added to normal lymphocytes cultures showed a dramatic inhibitory effect in only two out of nine cases. A follow-up study has strongly suggested that RA lymphocytes could increase their in vitro antibody response upon treatment.", "contents": "Depressed primary in vitro antibody response in rheumatoid arthritis. We have studied the primary in vitro antibody response toward a hapten in cultures of peripheral blood lymphocytes from twenty-two patients suffering from regular rheumatoid arthritis (RA). These patients were not receiving immunosuppressive drugs or corticosteroids and had not taken Aspirin or non-steroidal anti-inflammatory agents for at least 72 hr. The control groups included thirty-two healthy subjects and twenty-seven control patients. The mean anti-TNP response of the RA patients was significantly lower than that of both control groups. No pre-existing anti-TNP or IgG response could be detected. A search for suppressor cells in co-cultures of RA and normal lymphocytes was negative. On the contrary, the extent of allogeneic enhancement in such co-cultures was comparable to that observed when control lymphocytes were co-cultured. RA serum added to normal lymphocytes cultures showed a dramatic inhibitory effect in only two out of nine cases. A follow-up study has strongly suggested that RA lymphocytes could increase their in vitro antibody response upon treatment."} {"id": "PMID:159150", "title": "The immunopathology of Hodgkin's disease.", "content": "Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified.", "contents": "The immunopathology of Hodgkin's disease. Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified."} {"id": "PMID:159154", "title": "Propanil-chloracne and methomyl toxicity in workers of a pesticide manufacturing plant.", "content": "In a survey of occupationally acquired disease in workers at a pesticide plant, we found that 11 (11%) of 102 workers had been hospitalized for illness related to chemical exposures; highest hospitalization rates occurred in packaging (27%), production (22%), and maintenance (9%) workers. Commonest causes of hospitalization were intoxication by the carbamate pesticide methomyl [1-(methylthio)ethylideneamino methyl carbamate], a reversible cholinesterase inhibitor, and methemoglobinemia following exposure to 3,4-dichloroaniline. On clinical evaluation, five (46%) of 11 packaging workers, the group with the highest exposure to methomyl, had experienced blurred vision or pupillary constriction. Seventeen (61%) of 28 production workers with exposure to dichloroaniline and propanil (3'4'-dichloropropionanilide) had chloracne, an acne-form dermatosis caused by the contaminant tetrachlorazobenzene in propanil and dichloroaniline. The chloracnegenic potentials of propanil and dichloroaniline were verified by rabbit ear tests. These findings reemphasize the hazards inherent in the the manufacture and formulation of pesticides and herbicides.", "contents": "Propanil-chloracne and methomyl toxicity in workers of a pesticide manufacturing plant. In a survey of occupationally acquired disease in workers at a pesticide plant, we found that 11 (11%) of 102 workers had been hospitalized for illness related to chemical exposures; highest hospitalization rates occurred in packaging (27%), production (22%), and maintenance (9%) workers. Commonest causes of hospitalization were intoxication by the carbamate pesticide methomyl [1-(methylthio)ethylideneamino methyl carbamate], a reversible cholinesterase inhibitor, and methemoglobinemia following exposure to 3,4-dichloroaniline. On clinical evaluation, five (46%) of 11 packaging workers, the group with the highest exposure to methomyl, had experienced blurred vision or pupillary constriction. Seventeen (61%) of 28 production workers with exposure to dichloroaniline and propanil (3'4'-dichloropropionanilide) had chloracne, an acne-form dermatosis caused by the contaminant tetrachlorazobenzene in propanil and dichloroaniline. The chloracnegenic potentials of propanil and dichloroaniline were verified by rabbit ear tests. These findings reemphasize the hazards inherent in the the manufacture and formulation of pesticides and herbicides."} {"id": "PMID:159155", "title": "Detection of environmental depigmenting substances.", "content": "We systematically screened the depigmenting capacity of several phenols, catechols and organic antioxidants. Clear-cut depigmentation was achieved with monomethyl ether of hydroquinone (MMH) and tertiary butyl catechol (TBC) using black guinea pigs and black mice as animal models. A goal was to establish a reliable in vivo method to demonstrate or to predict the depigmenting action of chemicals on mammalian melanocytes. There was no universal solvent or optimal body site, although all tested areas could be depigmented. Irritation induced by some vehicles and test materials produced false positive responses. False negative responses with known depigmenting chemicals were observed. Utilizing these observations, we propose a model for screening medicinal and industrial chemicals for depigmenting capacity.", "contents": "Detection of environmental depigmenting substances. We systematically screened the depigmenting capacity of several phenols, catechols and organic antioxidants. Clear-cut depigmentation was achieved with monomethyl ether of hydroquinone (MMH) and tertiary butyl catechol (TBC) using black guinea pigs and black mice as animal models. A goal was to establish a reliable in vivo method to demonstrate or to predict the depigmenting action of chemicals on mammalian melanocytes. There was no universal solvent or optimal body site, although all tested areas could be depigmented. Irritation induced by some vehicles and test materials produced false positive responses. False negative responses with known depigmenting chemicals were observed. Utilizing these observations, we propose a model for screening medicinal and industrial chemicals for depigmenting capacity."} {"id": "PMID:159151", "title": "Interdigital clavus: predisposition is the key factor of soft corns.", "content": "The soft corn is defined as an interdigital hyperkeratosis. Footwear contributes to interdigital corns when there is a congenital or acquired predisposing factor. These predisposing factors cause apposition of particular bony prominences between adjacent toes. The congenital factors include a short first metatarsal, a short fifth metatarsal, or third and fourth metatarsals of equal length. The acquired predisposing factors are hallux valgus and associated abduction, hammer deformity, burrowing and curling of the lesser toes. Sixty-five per cent of the 1,063 interdigital corns studied occurred in the fourth interspace. Seventy per cent of the fourth interspace corns occurred between the proximal interphalangeal joint of the fourth toe and distal interphalangeal joint of the fifth toe. Conservative treatment is recommended for most cases.", "contents": "Interdigital clavus: predisposition is the key factor of soft corns. The soft corn is defined as an interdigital hyperkeratosis. Footwear contributes to interdigital corns when there is a congenital or acquired predisposing factor. These predisposing factors cause apposition of particular bony prominences between adjacent toes. The congenital factors include a short first metatarsal, a short fifth metatarsal, or third and fourth metatarsals of equal length. The acquired predisposing factors are hallux valgus and associated abduction, hammer deformity, burrowing and curling of the lesser toes. Sixty-five per cent of the 1,063 interdigital corns studied occurred in the fourth interspace. Seventy per cent of the fourth interspace corns occurred between the proximal interphalangeal joint of the fourth toe and distal interphalangeal joint of the fifth toe. Conservative treatment is recommended for most cases."} {"id": "PMID:159152", "title": "Pathology of spastic muscle in cerebral palsy.", "content": "The histopathology of muscle in cerebral palsy has not been elucidated because correlated morphologic and biochemical data on normal pediatric muscles are insufficient to allow adequate correlation of pathologic findings. One hundred and eight muscle biopsies were taken during reconstructive operations on 85 patients. Normal values for pediatric muscles were obtained from a literature review and supplemented with our data on normal patients. Fiber sizes are normally different for children of different ages. Histochemical staining of enzyme systems demonstrate that adenosine triphosphatase staining, pre-incubated at pH 9.4, 4.6, AND 4.3 WAS USED FOR FIBer typing and fiber size. Depending on the muscle biopsied and the clinical status of the patient, there is a variety of patterns of type I and type II fiber atrophy, hypertrophy, and myopathy. In some cases, denervation changes are present to suggest nerve entrapment. Correlated clinical observations suggest type I fiber predominant muscles do not re-educate well when surgically transferred to perform a specified function.", "contents": "Pathology of spastic muscle in cerebral palsy. The histopathology of muscle in cerebral palsy has not been elucidated because correlated morphologic and biochemical data on normal pediatric muscles are insufficient to allow adequate correlation of pathologic findings. One hundred and eight muscle biopsies were taken during reconstructive operations on 85 patients. Normal values for pediatric muscles were obtained from a literature review and supplemented with our data on normal patients. Fiber sizes are normally different for children of different ages. Histochemical staining of enzyme systems demonstrate that adenosine triphosphatase staining, pre-incubated at pH 9.4, 4.6, AND 4.3 WAS USED FOR FIBer typing and fiber size. Depending on the muscle biopsied and the clinical status of the patient, there is a variety of patterns of type I and type II fiber atrophy, hypertrophy, and myopathy. In some cases, denervation changes are present to suggest nerve entrapment. Correlated clinical observations suggest type I fiber predominant muscles do not re-educate well when surgically transferred to perform a specified function."} {"id": "PMID:159156", "title": "The enzymatic replication of DNA.", "content": "Enzymatic mechanisms of DNA replication have been investigated using small bacteriophages as probes to illuminate the cellular systems upon which they must rely during infection. Conversion of the circular, single-stranded DNAs of phages M13, G4, and phi X174 to their duplex forms has revealed the participation of diverse ways to start a new chain and a complex DNA polymerase III holoenzyme upon which all these systems depend for chain elongation. The phi X174 system, which is the most exacting and revealing of the host chromosomal replication pattern, includes at least twenty polypeptides for making the viral DNA into a duplex and multiplying the duplex. Resolution and purification of these numerous proteins is in train and their reconstitution into a \"replisome\"-like structure is envisioned.", "contents": "The enzymatic replication of DNA. Enzymatic mechanisms of DNA replication have been investigated using small bacteriophages as probes to illuminate the cellular systems upon which they must rely during infection. Conversion of the circular, single-stranded DNAs of phages M13, G4, and phi X174 to their duplex forms has revealed the participation of diverse ways to start a new chain and a complex DNA polymerase III holoenzyme upon which all these systems depend for chain elongation. The phi X174 system, which is the most exacting and revealing of the host chromosomal replication pattern, includes at least twenty polypeptides for making the viral DNA into a duplex and multiplying the duplex. Resolution and purification of these numerous proteins is in train and their reconstitution into a \"replisome\"-like structure is envisioned."} {"id": "PMID:159158", "title": "Determination of left ventricular wall thickening in patients with chronic systemic hypertension. Correlation of electrocardiography and echocardiography.", "content": "M-mode echocardiography was performed in 81 patients with chronic arterial hypertension in order to determine the specificity and sensitivity of the various ECG criteria used for diagnosing left ventricular hypertrophy (LVH) in the determination of left ventricular wall thickening (LVWT). Fifteen popular ECG criteria were studied and showed to be highly specific for LVWT (90 percent to 100 percent). TV1 greater than TV6, RV8 greater than 20 mm and SV1 + Rmax V5 or V6 greater than 35 mm were the most sensitive criteria (69 percent, 54 percent, and 52 percent respectively). The popular limb lead criteria for LVH were less sensitive than the precordial lead criteria in the determination of LVWT. The Estes point system, although less sensitive than some of the other voltage criteria, showed an absolute specificity for LVWT. The ST segment deviation with strain pattern was found in 46 percent of patients with LVWT. An isolated ST segment deviation without any other voltage criterion reflected at most only mild wall thickening. Six patients with LVWT had normal ECG; all of them were categorized in the mild LVWT group. Left axis deviation was found to be a poor indicator of wall thickening in uncomplicated hypertensive patients.", "contents": "Determination of left ventricular wall thickening in patients with chronic systemic hypertension. Correlation of electrocardiography and echocardiography. M-mode echocardiography was performed in 81 patients with chronic arterial hypertension in order to determine the specificity and sensitivity of the various ECG criteria used for diagnosing left ventricular hypertrophy (LVH) in the determination of left ventricular wall thickening (LVWT). Fifteen popular ECG criteria were studied and showed to be highly specific for LVWT (90 percent to 100 percent). TV1 greater than TV6, RV8 greater than 20 mm and SV1 + Rmax V5 or V6 greater than 35 mm were the most sensitive criteria (69 percent, 54 percent, and 52 percent respectively). The popular limb lead criteria for LVH were less sensitive than the precordial lead criteria in the determination of LVWT. The Estes point system, although less sensitive than some of the other voltage criteria, showed an absolute specificity for LVWT. The ST segment deviation with strain pattern was found in 46 percent of patients with LVWT. An isolated ST segment deviation without any other voltage criterion reflected at most only mild wall thickening. Six patients with LVWT had normal ECG; all of them were categorized in the mild LVWT group. Left axis deviation was found to be a poor indicator of wall thickening in uncomplicated hypertensive patients."} {"id": "PMID:159159", "title": "An unusual cause for mitral valve fluttering.", "content": "A 23-year-old patient with patent ductus arteriosus had coarse diastolic fluttering of the mitral valve leaflets on the echocardiogram in the absence of usual causes.", "contents": "An unusual cause for mitral valve fluttering. A 23-year-old patient with patent ductus arteriosus had coarse diastolic fluttering of the mitral valve leaflets on the echocardiogram in the absence of usual causes."} {"id": "PMID:159160", "title": "Pneumopericardium following laparoscopy.", "content": "There have been no published reports of pneumopericardium complicating laparoscopy. Following an apparently uncomplicated laparoscopy, a 35-year-old woman developed pneumopericardium associated with subcutaneous emphysema of the neck. This resolved without specific therapy and without sequelae.", "contents": "Pneumopericardium following laparoscopy. There have been no published reports of pneumopericardium complicating laparoscopy. Following an apparently uncomplicated laparoscopy, a 35-year-old woman developed pneumopericardium associated with subcutaneous emphysema of the neck. This resolved without specific therapy and without sequelae."} {"id": "PMID:159167", "title": "[Electrocardiographic and histomorphological changes in the myocardium of rats with Selye's experimental hypertension].", "content": "The authors described electrocardiographic and histomorphological changes in white rats with coarctation hypertention, induced by the method of Selye. The electrocardiographic changes were manifested as prologation of preauricular-ventricular conduction time, dislocation of the intermediate part ST to the isoelectrical line, low, negative or biphasic T-wave at the initial stages of the experiment, but after the thirthieth day there was a pathologic Q-wave, a reduced voltage of the steap curves and manifested left type of ECG in the majority of the experimental animals. Histomorphological and histochemical study on thmyocardium revealed in the beginning of the experiment mainly lesion changes, but sign of myocardial hypertrophy and manifested difuse and/or focal myocardial fibrosis on the 30th to the 90th day of the experiment.", "contents": "[Electrocardiographic and histomorphological changes in the myocardium of rats with Selye's experimental hypertension]. The authors described electrocardiographic and histomorphological changes in white rats with coarctation hypertention, induced by the method of Selye. The electrocardiographic changes were manifested as prologation of preauricular-ventricular conduction time, dislocation of the intermediate part ST to the isoelectrical line, low, negative or biphasic T-wave at the initial stages of the experiment, but after the thirthieth day there was a pathologic Q-wave, a reduced voltage of the steap curves and manifested left type of ECG in the majority of the experimental animals. Histomorphological and histochemical study on thmyocardium revealed in the beginning of the experiment mainly lesion changes, but sign of myocardial hypertrophy and manifested difuse and/or focal myocardial fibrosis on the 30th to the 90th day of the experiment."} {"id": "PMID:159168", "title": "[Organ cultures of human embryonic and fetal cartilage tissue (histological and histochemical studies)].", "content": "The author examined histologically and histochemically the peculiarities of tendon tissue of human embryos and fetuses. Inferences were made that under the conditions of organ culture for 7 days in the explanted tendon pieces there were histological peculiarities, characteristic of the reactions of the embryonal tendon tissue in the preparation and of the ossification with formation of \"a zone of cellular columns\". Processes of ossification were not observed which is explained by the lack of vascular in the explants. He found a reduced amount of acid glycosaminoglycans, an increase of the amount of neutral mucopolysaccharides and topographic redistribution of lipids and glycogen contrary to the data, observed in the control tissues.", "contents": "[Organ cultures of human embryonic and fetal cartilage tissue (histological and histochemical studies)]. The author examined histologically and histochemically the peculiarities of tendon tissue of human embryos and fetuses. Inferences were made that under the conditions of organ culture for 7 days in the explanted tendon pieces there were histological peculiarities, characteristic of the reactions of the embryonal tendon tissue in the preparation and of the ossification with formation of \"a zone of cellular columns\". Processes of ossification were not observed which is explained by the lack of vascular in the explants. He found a reduced amount of acid glycosaminoglycans, an increase of the amount of neutral mucopolysaccharides and topographic redistribution of lipids and glycogen contrary to the data, observed in the control tissues."} {"id": "PMID:159170", "title": "Evidence for divergent glucose effects on calcium metabolism in pancreatic beta- and alpha 2-cells.", "content": "Elucidation of the role of Ca2+ in the secretion of insulin and glucagon is complicated by the presence of different types of cells in the pancreatic islets. Visualization of calcium in sections of guinea pig pancreas with the histochemical reagent glyoxal bis-2-hydroxyanil revealed the most intense staining in the endocrine part but no differences between various islet cell types. A procedure for eliminating the majority of the beta-cells by streptozotocin injection in the guinea pig enabled a comparison of collagenase-isolated islets rich in alpha 2-cells with islets from untreated animals rich in beta-cells. The latter islets contained 24.6 +/- 2.4 mmol calcium/kg dry wt, as estimated by flameless atomic absorption spectrophotometry. This is twice as much as noted for the exocrine pancreas or the islets rich in alpha 2-cells. After storage for 3 days in culture medium, the two types of islets contained similar amounts of calcium. The cultured islets displayed differences related to cellular composition when measuring the incorporation of 45Ca into a lanthanum-nondisplaceable (intracellular) pool. In the presence of 3 mM glucose, more 45Ca was incorporated into the islets rich in alpha 2-cells. Increasing the glucose concentration to 20 mM with or without further addition of 30 U/liter bovine insulin was without effect on the 45Ca uptake into the islets rich in alpha 2-cells but stimulated that into islets rich in beta-cells. The different calcium dependence on glucose in the two types of islets may indicate that increased uptake of Ca2+ is a component of the mechanism for the secretion of both insulin and glucagon.", "contents": "Evidence for divergent glucose effects on calcium metabolism in pancreatic beta- and alpha 2-cells. Elucidation of the role of Ca2+ in the secretion of insulin and glucagon is complicated by the presence of different types of cells in the pancreatic islets. Visualization of calcium in sections of guinea pig pancreas with the histochemical reagent glyoxal bis-2-hydroxyanil revealed the most intense staining in the endocrine part but no differences between various islet cell types. A procedure for eliminating the majority of the beta-cells by streptozotocin injection in the guinea pig enabled a comparison of collagenase-isolated islets rich in alpha 2-cells with islets from untreated animals rich in beta-cells. The latter islets contained 24.6 +/- 2.4 mmol calcium/kg dry wt, as estimated by flameless atomic absorption spectrophotometry. This is twice as much as noted for the exocrine pancreas or the islets rich in alpha 2-cells. After storage for 3 days in culture medium, the two types of islets contained similar amounts of calcium. The cultured islets displayed differences related to cellular composition when measuring the incorporation of 45Ca into a lanthanum-nondisplaceable (intracellular) pool. In the presence of 3 mM glucose, more 45Ca was incorporated into the islets rich in alpha 2-cells. Increasing the glucose concentration to 20 mM with or without further addition of 30 U/liter bovine insulin was without effect on the 45Ca uptake into the islets rich in alpha 2-cells but stimulated that into islets rich in beta-cells. The different calcium dependence on glucose in the two types of islets may indicate that increased uptake of Ca2+ is a component of the mechanism for the secretion of both insulin and glucagon."} {"id": "PMID:159171", "title": "Plasma levels of 16 alpha-hydroxypregnenolone, 16 alpha-hydroxyprogesterone and 16 alpha-hydroxydehydroepiandrosterone in the fetus and neonates.", "content": "Simultaneous determination of unconjugated 16 alpha-hydroxypregnenolone (16 alphaOH-Preg), 16 alpha-hydroxyprogesterone (16 alphaOH-Prog) and 16 alpha-hydroxydehydroepiandrosterone (16 alphaOH-DHEA) in fetal and neonatal plasma was performed utilizing a newly developed radioimmunoassay. In all neonates, the three 16 alpha-hydroxysteroid levels were consistently higher in umbilical cord plasma than in the maternal peripheral circulation. 16 alpha-OH-Preg in the umbilical arterial plasma increased from 11.2 +/- 3.1 at 24 weeks to 29.7 +/- 12.0 ng/ml at term, 16 alphaOH-Prog from 15.5 +/- 3.2 to 34.3 +/- 11.0 ng/ml and 16 alphaOH-DHEA from 5.1 +/- 1.2 to 5.9 +/- 1.0 ng/ml. In the anencephalic neonates, only 16 alphaOH-Preg showed an increase pattern under ACTH priming. 16 alpha-OH-Preg levels for normal full term neonates remain relatively constant at the first 24 hr and show a slight decrease at 3 days post partum. In small full term neonates, 16 alphaOH-Preg levels in umbilical arterial plasma are considerably higher than in normal neonates and remain at roughly equivalent levels for the first 5 days post partum. 16 alphaOH-Prog and 16 alphaOH-DHEA levels in umbilical arterial plasma in normal and small full term neonates are almost equal and both groups show a rapid decrease during the first 24 hr. Comparison with findings of the three 16 alpha-hydroxysteroids in fetal and neonatal plasma is discussed.", "contents": "Plasma levels of 16 alpha-hydroxypregnenolone, 16 alpha-hydroxyprogesterone and 16 alpha-hydroxydehydroepiandrosterone in the fetus and neonates. Simultaneous determination of unconjugated 16 alpha-hydroxypregnenolone (16 alphaOH-Preg), 16 alpha-hydroxyprogesterone (16 alphaOH-Prog) and 16 alpha-hydroxydehydroepiandrosterone (16 alphaOH-DHEA) in fetal and neonatal plasma was performed utilizing a newly developed radioimmunoassay. In all neonates, the three 16 alpha-hydroxysteroid levels were consistently higher in umbilical cord plasma than in the maternal peripheral circulation. 16 alpha-OH-Preg in the umbilical arterial plasma increased from 11.2 +/- 3.1 at 24 weeks to 29.7 +/- 12.0 ng/ml at term, 16 alphaOH-Prog from 15.5 +/- 3.2 to 34.3 +/- 11.0 ng/ml and 16 alphaOH-DHEA from 5.1 +/- 1.2 to 5.9 +/- 1.0 ng/ml. In the anencephalic neonates, only 16 alphaOH-Preg showed an increase pattern under ACTH priming. 16 alpha-OH-Preg levels for normal full term neonates remain relatively constant at the first 24 hr and show a slight decrease at 3 days post partum. In small full term neonates, 16 alphaOH-Preg levels in umbilical arterial plasma are considerably higher than in normal neonates and remain at roughly equivalent levels for the first 5 days post partum. 16 alphaOH-Prog and 16 alphaOH-DHEA levels in umbilical arterial plasma in normal and small full term neonates are almost equal and both groups show a rapid decrease during the first 24 hr. Comparison with findings of the three 16 alpha-hydroxysteroids in fetal and neonatal plasma is discussed."} {"id": "PMID:159172", "title": "Clustering of chromosomal aneuploidy and tracing of nondisjunction in man.", "content": "Chromosomal aneuploidy is the most frequent genetic damage observed in newborn children and originates as a rule from nondisjunction during maternal or paternal germ cell development. The error of chromosome segregation could be allocated in the past--at least in cases of 47,XXY--to maternal meiosis I (50%) or meiosis II (10%) and to paternal meiosis I (40%). Recent cytological improvements with various banding techniques enabled a further study on the origin of nondisjunction. Summarizing the published data one can argue that errors in Downs' syndrome are most often due to cleavage errors during maternal meiosis I. Approximately 70% of errors occur in oogenesis and only 30% in spermatogenesis. Maternal meiosis I seems also to be involved in most cases of fetal trisomy 16. Such a preferential missegregation of chromosomes offers the possibility of studying more closely the very mechanisms of nondisjunction in mammalian meiosis and early cleavages.", "contents": "Clustering of chromosomal aneuploidy and tracing of nondisjunction in man. Chromosomal aneuploidy is the most frequent genetic damage observed in newborn children and originates as a rule from nondisjunction during maternal or paternal germ cell development. The error of chromosome segregation could be allocated in the past--at least in cases of 47,XXY--to maternal meiosis I (50%) or meiosis II (10%) and to paternal meiosis I (40%). Recent cytological improvements with various banding techniques enabled a further study on the origin of nondisjunction. Summarizing the published data one can argue that errors in Downs' syndrome are most often due to cleavage errors during maternal meiosis I. Approximately 70% of errors occur in oogenesis and only 30% in spermatogenesis. Maternal meiosis I seems also to be involved in most cases of fetal trisomy 16. Such a preferential missegregation of chromosomes offers the possibility of studying more closely the very mechanisms of nondisjunction in mammalian meiosis and early cleavages."} {"id": "PMID:159173", "title": "Down's syndrome and maternal age in British Columbia, 1972--75.", "content": "The occurrence of Down's syndrome in British Columbia during the period 1972-75 is analyzed with respect to maternal age distribution. This period is compared with previously studied periods. No marked trends are evident in the various age group-specific rates studied. The significance of these findings is discussed in connection with a possible role of environmental nutagens in induction of Down's syndrome and the maternal age effect.", "contents": "Down's syndrome and maternal age in British Columbia, 1972--75. The occurrence of Down's syndrome in British Columbia during the period 1972-75 is analyzed with respect to maternal age distribution. This period is compared with previously studied periods. No marked trends are evident in the various age group-specific rates studied. The significance of these findings is discussed in connection with a possible role of environmental nutagens in induction of Down's syndrome and the maternal age effect."} {"id": "PMID:159174", "title": "Cell-free synthesis of the mitochondrial ADP/ATP carrier protein of Neurospora crassa.", "content": "ADP/ATP carrier protein was synthesized in heterologous cell-free systems programmed with Neurospora poly(A)-containing RNA and homologous cell-free systems from Neurospora. The apparent molecular weight of the product obtained in vitro was the same as that of the authentic mitochondrial protein. The primary translation product obtained in reticulocyte lysates starts with formylmethionine when formylated initiator methionyl-tRNA (fMet-tRNAfMet) was present. The product synthesized in vitro was released from the ribosomes into the postribosomal supernatant. The evidence presented indicates that the ADP/ATP carrier is synthesized as a polypeptide with the same molecular weight as the mature monomeric protein and does not carry an additional sequence.", "contents": "Cell-free synthesis of the mitochondrial ADP/ATP carrier protein of Neurospora crassa. ADP/ATP carrier protein was synthesized in heterologous cell-free systems programmed with Neurospora poly(A)-containing RNA and homologous cell-free systems from Neurospora. The apparent molecular weight of the product obtained in vitro was the same as that of the authentic mitochondrial protein. The primary translation product obtained in reticulocyte lysates starts with formylmethionine when formylated initiator methionyl-tRNA (fMet-tRNAfMet) was present. The product synthesized in vitro was released from the ribosomes into the postribosomal supernatant. The evidence presented indicates that the ADP/ATP carrier is synthesized as a polypeptide with the same molecular weight as the mature monomeric protein and does not carry an additional sequence."} {"id": "PMID:159175", "title": "An electrophoretic study of native myosin isozymes and of their subunit content.", "content": "Myosin polymorphism in muscles has been studied by a variety of electrophoretic techniques, in non-dissociating and in dissociating conditions. The analysis of myosin isozymes in the native state was achieved in pyrophosphate buffer and required only minute amounts of protein; identical results were obtained with purified or crudely extracted myosin. The determination of the subunit content of each isozyme was done in the presence of sodium dodecyl sulphate or urea for light chain, and in a phenol, acetic acid and urea system for heavy chain screening. Electrophoresis in non-dissociating conditions has led to the separation of up to a dozen of myosin isozymes, differing in mobilities by as much as 30%. Muscle specificity of myosin was clearly established. Apart from a few exceptions, all the muscles tested were shown to contain more than one myosin species; fast-twitch muscles for instance all contained the same three isozymes, but in variable ratios. Class specificity of myosin appeared related to the relative proportions of isozymes in a given muscle. A second electrophoresis in dissociating solvents of the myosin bands first resolved in pyrophosphate buffer has then allowed a further characterization of the various isozymes. The differences in mobilities observed in the native state were shown to come either from the light chains, or from the heavy chains, or from both. The first case was illustrated by the three species present in fast muscles, which were shown to correspond to three alkali light-chain isozymes, the heterodimer representing in some instances up to 40% of the total. Next to light-chain muscle type specificity, electrophoresis in the phenol, acetic acid, urea system has led to the detection of differences in the heavy chains of fast, slow and cardiac myosins. The application of these various electrophoretic techniques to the analysis of the modification of myosin isozymes during development or in pathology studies can be considered.", "contents": "An electrophoretic study of native myosin isozymes and of their subunit content. Myosin polymorphism in muscles has been studied by a variety of electrophoretic techniques, in non-dissociating and in dissociating conditions. The analysis of myosin isozymes in the native state was achieved in pyrophosphate buffer and required only minute amounts of protein; identical results were obtained with purified or crudely extracted myosin. The determination of the subunit content of each isozyme was done in the presence of sodium dodecyl sulphate or urea for light chain, and in a phenol, acetic acid and urea system for heavy chain screening. Electrophoresis in non-dissociating conditions has led to the separation of up to a dozen of myosin isozymes, differing in mobilities by as much as 30%. Muscle specificity of myosin was clearly established. Apart from a few exceptions, all the muscles tested were shown to contain more than one myosin species; fast-twitch muscles for instance all contained the same three isozymes, but in variable ratios. Class specificity of myosin appeared related to the relative proportions of isozymes in a given muscle. A second electrophoresis in dissociating solvents of the myosin bands first resolved in pyrophosphate buffer has then allowed a further characterization of the various isozymes. The differences in mobilities observed in the native state were shown to come either from the light chains, or from the heavy chains, or from both. The first case was illustrated by the three species present in fast muscles, which were shown to correspond to three alkali light-chain isozymes, the heterodimer representing in some instances up to 40% of the total. Next to light-chain muscle type specificity, electrophoresis in the phenol, acetic acid, urea system has led to the detection of differences in the heavy chains of fast, slow and cardiac myosins. The application of these various electrophoretic techniques to the analysis of the modification of myosin isozymes during development or in pathology studies can be considered."} {"id": "PMID:159180", "title": "Heart muscle disease among adult Nigerians: role of nutritional factors in its aetiology.", "content": "A study of 44 Nigerians with heart muscle disease defined as congestive cardiac failure and cardiac enlargement of unknown cause with a presenting diastolic blood pressure of not more than 100 mm Hg has shown 20 were alcoholics. 12 of these belonged to the high socioeconomic class. 17 were thiamine deficient; 11 of these consumed alcohol excessively and 8 of the 11 belonged to the high socioeconomic class. Only 3 alcoholics were identified in 52 controls. None of the 3 patients was thiamine deficient but 10 others were. Only 1 patient with heart muscle disease had a reversible high output cardiac failure. The mean serum albumin of the patients with heart muscle disease was significantly lower than controls. There was no significant difference between the mean levels of serum potassium in the study group and controls. It is concluded that chronic alcoholism is not rare among Nigerians with heart muscle disease. Although there is no convincing evidence to show that malnutrition or thiamine deficiency could in themselves cause the chronic myocardial failure seen in heart muscle disease, they could be conditioning factors which increase the susceptibility of the heart to other injurious agents.", "contents": "Heart muscle disease among adult Nigerians: role of nutritional factors in its aetiology. A study of 44 Nigerians with heart muscle disease defined as congestive cardiac failure and cardiac enlargement of unknown cause with a presenting diastolic blood pressure of not more than 100 mm Hg has shown 20 were alcoholics. 12 of these belonged to the high socioeconomic class. 17 were thiamine deficient; 11 of these consumed alcohol excessively and 8 of the 11 belonged to the high socioeconomic class. Only 3 alcoholics were identified in 52 controls. None of the 3 patients was thiamine deficient but 10 others were. Only 1 patient with heart muscle disease had a reversible high output cardiac failure. The mean serum albumin of the patients with heart muscle disease was significantly lower than controls. There was no significant difference between the mean levels of serum potassium in the study group and controls. It is concluded that chronic alcoholism is not rare among Nigerians with heart muscle disease. Although there is no convincing evidence to show that malnutrition or thiamine deficiency could in themselves cause the chronic myocardial failure seen in heart muscle disease, they could be conditioning factors which increase the susceptibility of the heart to other injurious agents."} {"id": "PMID:159181", "title": "Evaluation of left ventricular performance in aortic stenosis, aortic regurgitation and mitral regurgitation from the stroke work/left ventricular mass ratio.", "content": "Evaluation of left ventricular performance in aortic stenosis, aortic regurgitation and mitral regurgitation from the stroke work/left ventricular mass ratio. Europ. J. Cardiol., 10/4, 279--294. 132 patients with a pure valvular dysfunction affecting a single orifice, namely aortic stenosis, aortic or mitral regurgitation, were studied. All patients, including 20 control subjects, underwent hemodynamic examination of both right and left heart chambers including left cineangiography. Using the stroke work index/myocardial mass ratio (SWI/MLV), for which the limits in normal subjects are narrow (0.81 +/- 0.03 . g-1) it was possible to divide these patients into three groups: Group I (SWI/MLV greater than 0.87 gm . g-1) characterized by a proportionately greater increase in stroke work index than myocardial mass (hyperfunctioning ventricle). Group II (0.87 gm . g-1 greater than or equal to SWI/MLV greater than or equal to 0.75 gm . g-1) characterized by a parallel increase in stroke work index and myocardial mass (normally functioning ventricle). Group III (SWI/MLV less than 0.75 gm . g-1) for which the increase in myocardial mass was proportionately greater than that of the stroke work index (hypofunctioning ventricle). As one progresses from group I to III, there is a concomitant fall in ventricular function with decreased mean velocity of circumferential fiber shortening (VCF), ejection fraction (EF) and increased enddiastolic volume (EDV) together with the hypertrophy of the left ventricle during the last stage. We conclude that the SWI/MLV ratio is an easy to calculate index, independent of the unerlying dysfunction, which evaluates left ventricular function by taking into account the myocardial mass.", "contents": "Evaluation of left ventricular performance in aortic stenosis, aortic regurgitation and mitral regurgitation from the stroke work/left ventricular mass ratio. Evaluation of left ventricular performance in aortic stenosis, aortic regurgitation and mitral regurgitation from the stroke work/left ventricular mass ratio. Europ. J. Cardiol., 10/4, 279--294. 132 patients with a pure valvular dysfunction affecting a single orifice, namely aortic stenosis, aortic or mitral regurgitation, were studied. All patients, including 20 control subjects, underwent hemodynamic examination of both right and left heart chambers including left cineangiography. Using the stroke work index/myocardial mass ratio (SWI/MLV), for which the limits in normal subjects are narrow (0.81 +/- 0.03 . g-1) it was possible to divide these patients into three groups: Group I (SWI/MLV greater than 0.87 gm . g-1) characterized by a proportionately greater increase in stroke work index than myocardial mass (hyperfunctioning ventricle). Group II (0.87 gm . g-1 greater than or equal to SWI/MLV greater than or equal to 0.75 gm . g-1) characterized by a parallel increase in stroke work index and myocardial mass (normally functioning ventricle). Group III (SWI/MLV less than 0.75 gm . g-1) for which the increase in myocardial mass was proportionately greater than that of the stroke work index (hypofunctioning ventricle). As one progresses from group I to III, there is a concomitant fall in ventricular function with decreased mean velocity of circumferential fiber shortening (VCF), ejection fraction (EF) and increased enddiastolic volume (EDV) together with the hypertrophy of the left ventricle during the last stage. We conclude that the SWI/MLV ratio is an easy to calculate index, independent of the unerlying dysfunction, which evaluates left ventricular function by taking into account the myocardial mass."} {"id": "PMID:159182", "title": "Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol.", "content": "This paper reports a study of the bronchodilator effects of doses of the beta 2 agonist fenoterol and the muscarinic blocker ipratropium suitable for administering in combination as a standard dose of two discharges from a single metered-dose pressurised aerosol. In 12 middle-aged bronchitics who had already been shown to respond to both types of drug the combination was almost always a little (6% on average) more effective than either drug singly. It is possible that an equal or better effect could have been obtained if fenoterol or perhaps ipratropium had been given alone in an individually determined maximally effective dose.", "contents": "Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol. This paper reports a study of the bronchodilator effects of doses of the beta 2 agonist fenoterol and the muscarinic blocker ipratropium suitable for administering in combination as a standard dose of two discharges from a single metered-dose pressurised aerosol. In 12 middle-aged bronchitics who had already been shown to respond to both types of drug the combination was almost always a little (6% on average) more effective than either drug singly. It is possible that an equal or better effect could have been obtained if fenoterol or perhaps ipratropium had been given alone in an individually determined maximally effective dose."} {"id": "PMID:159183", "title": "Suppressor cells and immunodeficiency in (NZB x NZW)F1 hybrid mice.", "content": "Old (15-20 month) male (NZB x NZW)F1 (B/W) mice have severely impaired spleen cell reactivity to phytohemagglutinin (PHA), a mitogen which stimulates mainly T lymphocytes. Spleen cells from old mice markedly suppressed the PHA response of splenocytes from young (3-4 month) B/W males. Similar suppressor activity was not present in the spleens of old mice of four nonautoimmune strains. The suppressor activity of old B/W spleen cells was mediated by a nonphagocytic, radioresistant, mononuclear leukocyte. Although this cell was eluted in the \"T lymphocyte\" fraction of nylon wool colums, it was not sensitive to treatment with anti-Thy-1 antiserum and complement. Suppressor activity was lost after 18 h incubation at 37 degrees C in tissue culture medium. Supernatants of these overnight cultures had no suppressive effect on fresh young B/W spleen cells. Old B/W spleen cells suppressed PHA reactivity more than concanavalin A or lipopolysaccharide reactivity. Kinetic studies demonstrated an increasing suppression with time over 72 h of culture. This study demonstrate that the severely impaired PHA reactivity of old B/W mice is mediated, at least in part, by active suppression.", "contents": "Suppressor cells and immunodeficiency in (NZB x NZW)F1 hybrid mice. Old (15-20 month) male (NZB x NZW)F1 (B/W) mice have severely impaired spleen cell reactivity to phytohemagglutinin (PHA), a mitogen which stimulates mainly T lymphocytes. Spleen cells from old mice markedly suppressed the PHA response of splenocytes from young (3-4 month) B/W males. Similar suppressor activity was not present in the spleens of old mice of four nonautoimmune strains. The suppressor activity of old B/W spleen cells was mediated by a nonphagocytic, radioresistant, mononuclear leukocyte. Although this cell was eluted in the \"T lymphocyte\" fraction of nylon wool colums, it was not sensitive to treatment with anti-Thy-1 antiserum and complement. Suppressor activity was lost after 18 h incubation at 37 degrees C in tissue culture medium. Supernatants of these overnight cultures had no suppressive effect on fresh young B/W spleen cells. Old B/W spleen cells suppressed PHA reactivity more than concanavalin A or lipopolysaccharide reactivity. Kinetic studies demonstrated an increasing suppression with time over 72 h of culture. This study demonstrate that the severely impaired PHA reactivity of old B/W mice is mediated, at least in part, by active suppression."} {"id": "PMID:159184", "title": "Ontogeny of cells involved in the suppressor circuit of the immune response.", "content": "Some macrophage (M phi) cell surface structures which bind T cell-derived factors remain intact after the M phi are killed by heating at 56 degrees C (but not 72 degrees C) for 45 min. As a result, appropriately killed M phi (HK M phi) can act as competitive antagonists for those M phi functions which are involved in binding and active presentation of T cell-derived regulatory signals. By blocking the transmission of these signals with HK M phi, we have found that the spleens of newborn mice contain considerable numbers of \"latent\" helper cells whose activity is not ordinarily seen because it is overridden by suppressor mechanisms. Similarities between these neonatal helper cells and a subset of adult T helper \"inducer\" cells (cell surface phenotype Ly-1+; Ly-2-, 3-; IJ+; Qa 1+), whose activity appears in significant numbers only after immunization, are described.", "contents": "Ontogeny of cells involved in the suppressor circuit of the immune response. Some macrophage (M phi) cell surface structures which bind T cell-derived factors remain intact after the M phi are killed by heating at 56 degrees C (but not 72 degrees C) for 45 min. As a result, appropriately killed M phi (HK M phi) can act as competitive antagonists for those M phi functions which are involved in binding and active presentation of T cell-derived regulatory signals. By blocking the transmission of these signals with HK M phi, we have found that the spleens of newborn mice contain considerable numbers of \"latent\" helper cells whose activity is not ordinarily seen because it is overridden by suppressor mechanisms. Similarities between these neonatal helper cells and a subset of adult T helper \"inducer\" cells (cell surface phenotype Ly-1+; Ly-2-, 3-; IJ+; Qa 1+), whose activity appears in significant numbers only after immunization, are described."} {"id": "PMID:159185", "title": "Studies on T lymphocyte activation II. The target cells for concanavalin A-induced growth factors.", "content": "Growth factors contained in Con A(concanavalin A)-conditioned media (CM) maintain exponential growth in T cell blasts derived from mitogen stimulation of spleen cells with Con A, phytohemagglutinin, lentil lectin and pokeweed mitogen (PWM), as well as from mixed lymphocyte reactions to H-2D or I-C-encoded determinants and from non-H-2 Mls locus-controlled reactions. Such growth factors are strictly T cell blast-specific, inasmuch as they do not stimulate resting, small T or B lymphocytes nor B cell blasts generated by lipopolysaccharide or lipoprotein activation. The responsiveness of T cell blasts to CM appears to be the result of the availability on the cell surface of an acceptor site for growth factors which is not expressed in resting cells, because T cell blasts, but not small spleen cells, absorb out the growth-promoting activity contained in CM. Furthermore, lectins such as Con A and PWM interfere with the blast surface membrane in such a way that they inhibit the response to growth factors. Finally, there is no detectable allotypic or isotypic restriction in the activity of Con A-CM on a variety of target T cell blasts.", "contents": "Studies on T lymphocyte activation II. The target cells for concanavalin A-induced growth factors. Growth factors contained in Con A(concanavalin A)-conditioned media (CM) maintain exponential growth in T cell blasts derived from mitogen stimulation of spleen cells with Con A, phytohemagglutinin, lentil lectin and pokeweed mitogen (PWM), as well as from mixed lymphocyte reactions to H-2D or I-C-encoded determinants and from non-H-2 Mls locus-controlled reactions. Such growth factors are strictly T cell blast-specific, inasmuch as they do not stimulate resting, small T or B lymphocytes nor B cell blasts generated by lipopolysaccharide or lipoprotein activation. The responsiveness of T cell blasts to CM appears to be the result of the availability on the cell surface of an acceptor site for growth factors which is not expressed in resting cells, because T cell blasts, but not small spleen cells, absorb out the growth-promoting activity contained in CM. Furthermore, lectins such as Con A and PWM interfere with the blast surface membrane in such a way that they inhibit the response to growth factors. Finally, there is no detectable allotypic or isotypic restriction in the activity of Con A-CM on a variety of target T cell blasts."} {"id": "PMID:159188", "title": "Mg2+-ATPase defective mutant of Escherichia coli and thiamine transport.", "content": "Mg2+-ATPase deficient mutant of Escherichia coli showed an evident dependency of thiamine uptake on the oxidative metabolism of glucose, whereas the parent strain did not. In both cells, this uptake was completely inhibited by H+ conductors.", "contents": "Mg2+-ATPase defective mutant of Escherichia coli and thiamine transport. Mg2+-ATPase deficient mutant of Escherichia coli showed an evident dependency of thiamine uptake on the oxidative metabolism of glucose, whereas the parent strain did not. In both cells, this uptake was completely inhibited by H+ conductors."} {"id": "PMID:159194", "title": "Combined laparoscopy and minilaparotomy in the management of unruptured tubal pregnancy: a preliminary report.", "content": "Following laparoscopic diagnosis of unruptured tubal pregnancy, six patients underwent partial salpingectomy using a minilaprotomy technique. None of the patients had any complications resulting from the surgery. Four were discharged within 48 hours of surgery and the others on the 3rd postoperative day. When an ectopic pregnancy has been diagnosed before rupture the technique seems preferable, as it entails a less extensive hospital stay than does conventional laparotomy. The smaller incision is more comfortable and is cosmetically acceptable. The technique is relatively easy to use, and it is hoped that the minimal invasion of the peritoneal cavity will have a less deleterious effect on future fertility.", "contents": "Combined laparoscopy and minilaparotomy in the management of unruptured tubal pregnancy: a preliminary report. Following laparoscopic diagnosis of unruptured tubal pregnancy, six patients underwent partial salpingectomy using a minilaprotomy technique. None of the patients had any complications resulting from the surgery. Four were discharged within 48 hours of surgery and the others on the 3rd postoperative day. When an ectopic pregnancy has been diagnosed before rupture the technique seems preferable, as it entails a less extensive hospital stay than does conventional laparotomy. The smaller incision is more comfortable and is cosmetically acceptable. The technique is relatively easy to use, and it is hoped that the minimal invasion of the peritoneal cavity will have a less deleterious effect on future fertility."} {"id": "PMID:159195", "title": "Induction of suppressor cell mechanism in antilymphocyte serum-induced skin allograft tolerance in mice.", "content": "In the B10.D2 leads to B10.D2(M504) strain combination (H-2D incompatibility), 20--40% of skin allografts survive for more than 100 days in ALS-treated recipients. Allograft tolerance in ALS-treated recipients could not be abolished by adoptively transferred normal or immune syngeneic spleen cells, but it could be adoptively transferred by spleen or lymph node cells to sublethally irradiated syngeneic mice. The suppressive activity of transferred cell population markedly declined after treatment with anti Thy-1.2 serum and complement. Cells with suppressor activity could be demonstrated by adoptive transfers as early as 5 days after skin grafting and ALS treatment. The results showed that the long-term allograft-promoting effect of ALS was caused not only by a decrease in the graft-rejection cell potential of the recipients (as demonstrated by other authors earlier) but also by the activation of a T cell-mediated suppressor mechanism.", "contents": "Induction of suppressor cell mechanism in antilymphocyte serum-induced skin allograft tolerance in mice. In the B10.D2 leads to B10.D2(M504) strain combination (H-2D incompatibility), 20--40% of skin allografts survive for more than 100 days in ALS-treated recipients. Allograft tolerance in ALS-treated recipients could not be abolished by adoptively transferred normal or immune syngeneic spleen cells, but it could be adoptively transferred by spleen or lymph node cells to sublethally irradiated syngeneic mice. The suppressive activity of transferred cell population markedly declined after treatment with anti Thy-1.2 serum and complement. Cells with suppressor activity could be demonstrated by adoptive transfers as early as 5 days after skin grafting and ALS treatment. The results showed that the long-term allograft-promoting effect of ALS was caused not only by a decrease in the graft-rejection cell potential of the recipients (as demonstrated by other authors earlier) but also by the activation of a T cell-mediated suppressor mechanism."} {"id": "PMID:159197", "title": "[In vitro stimulation of peripheral blood lymphocytes with allogeneic lymphocytes or phytomitogens in patients with insulin-dependent diabetes mellitus (author's transl)].", "content": "The lymphocyte transformation response to the allogeneic lymphocytes (mixed lymphocyte culture, MLC) was determined in nineteen well-controlled insulin-dependent diabetics (IDD) and nineteen matched normal subjects. All possible combinations between lymphocytes from the patients and controls were mixed in both one-way and two-way MLC. From the results of one-way MLC, the stimulatory capacity (SC) and responding capacity (RC) of IDD lymphocytes were compared with those of normal lymphocytes as follows: (1) Nm leads to N: 10,538 +/- 3,937 N; normal lymphocytes (2) Nm leads to D: 8;466 +/- 5,387 D; IDD lymphocytes (3) Dm leads to N: 7,562 +/- 3,088 m; mitomycin-treated stimulating lymphocytes (4) Dm leads to D: 7,102 +/- 4,873 (leads to; stimulatory direction, results; M +/- SD cpm) IDD lymphocytes showed a marked depressive function as stimulators (SC, (1) -- (3)), but the RC of IDD lymphocytes was unchanged ((1) -- (2)). Phytomitogen-response was studied simultaneously for the same responding lymphocytes (N, D) of MLC. IDD lymphocytes exhibited significantly decreased responses to phytohemagglutinin P, pokeweed mitogen and concanavalin A.", "contents": "[In vitro stimulation of peripheral blood lymphocytes with allogeneic lymphocytes or phytomitogens in patients with insulin-dependent diabetes mellitus (author's transl)]. The lymphocyte transformation response to the allogeneic lymphocytes (mixed lymphocyte culture, MLC) was determined in nineteen well-controlled insulin-dependent diabetics (IDD) and nineteen matched normal subjects. All possible combinations between lymphocytes from the patients and controls were mixed in both one-way and two-way MLC. From the results of one-way MLC, the stimulatory capacity (SC) and responding capacity (RC) of IDD lymphocytes were compared with those of normal lymphocytes as follows: (1) Nm leads to N: 10,538 +/- 3,937 N; normal lymphocytes (2) Nm leads to D: 8;466 +/- 5,387 D; IDD lymphocytes (3) Dm leads to N: 7,562 +/- 3,088 m; mitomycin-treated stimulating lymphocytes (4) Dm leads to D: 7,102 +/- 4,873 (leads to; stimulatory direction, results; M +/- SD cpm) IDD lymphocytes showed a marked depressive function as stimulators (SC, (1) -- (3)), but the RC of IDD lymphocytes was unchanged ((1) -- (2)). Phytomitogen-response was studied simultaneously for the same responding lymphocytes (N, D) of MLC. IDD lymphocytes exhibited significantly decreased responses to phytohemagglutinin P, pokeweed mitogen and concanavalin A."} {"id": "PMID:159202", "title": "The intercellular distribution of mutations induced in oocytes of Drosophila melanogaster by chemical and physical mutagens.", "content": "When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such \"single\" and \"double mutations\". A theory is developed to show how a comparison between the expected and the observed frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogeneous or nonhomogeneous) of those agents.--Three agents were tested: FUdR (12.5, 50.5 and 81.0 micrograms/ml), mitomycin C (130.0 micrograms/ml) and X rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding, 104 single and three double mutations were obtained. All of the 50 mutations observed after X irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique.", "contents": "The intercellular distribution of mutations induced in oocytes of Drosophila melanogaster by chemical and physical mutagens. When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such \"single\" and \"double mutations\". A theory is developed to show how a comparison between the expected and the observed frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogeneous or nonhomogeneous) of those agents.--Three agents were tested: FUdR (12.5, 50.5 and 81.0 micrograms/ml), mitomycin C (130.0 micrograms/ml) and X rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding, 104 single and three double mutations were obtained. All of the 50 mutations observed after X irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique."} {"id": "PMID:159203", "title": "Organization of the qa gene cluster in Neurospora crassa: direction of transcription of the qa-3 gene.", "content": "In Neurospora crassa, the enzyme quinate (shikimate) dehydrogenase catalyzes the first reaction in the inducible quinic acid catabolic pathway and is encoded in the qa-3 gene of the qa cluster. In this cluster, the order of genes has been established as qa-1 qa-3 qa-4 qa-2. Amino-terminal sequences have been determined for purified quinate dehydrogenase from wild type and from UV-induced revertants in two different qa-3 mutants. These two mutants (M16 and M45) map at opposite ends of the qa-3 locus. In addition, mapping data (Caseet al. 1978) indicate that the end of the qa-3 gene specified by M45 is closer to the adjacent qa-1 gene than is the end specified by the M16 mutant site. In one of the revertants (R45 from qa-3 mutant M45), the aminoterminal sequence for the first ten amino acids is identical to that of wild type. The other revertant (R1 from qa-3 mutant M16) differs from wild type at the amino-terminal end by a single altered residue at position three in the sequence. The observed change involves the substitution of an isoleucine in M16-R1 for a proline in wild type. This substitution requires a two-nucleotide change in the corresponding wild-type codon.--The combined genetic and biochemical data indicate that the qa-3 mutants M16 and M45 carry amino acid substitutions near the amino-terminal and carboxyl-terminal ends of the quinate dehydrogenase enzyme, respectively. On this basis we conclude that transcription of the qa-3 gene proceeds from the end specified by the M16 mutant site in the direction of the qa-1 gene. It appears probable that transcription is initiated from a promoter site within the qa cluster, possibly immediately adjacent to the qa-3 gene.", "contents": "Organization of the qa gene cluster in Neurospora crassa: direction of transcription of the qa-3 gene. In Neurospora crassa, the enzyme quinate (shikimate) dehydrogenase catalyzes the first reaction in the inducible quinic acid catabolic pathway and is encoded in the qa-3 gene of the qa cluster. In this cluster, the order of genes has been established as qa-1 qa-3 qa-4 qa-2. Amino-terminal sequences have been determined for purified quinate dehydrogenase from wild type and from UV-induced revertants in two different qa-3 mutants. These two mutants (M16 and M45) map at opposite ends of the qa-3 locus. In addition, mapping data (Caseet al. 1978) indicate that the end of the qa-3 gene specified by M45 is closer to the adjacent qa-1 gene than is the end specified by the M16 mutant site. In one of the revertants (R45 from qa-3 mutant M45), the aminoterminal sequence for the first ten amino acids is identical to that of wild type. The other revertant (R1 from qa-3 mutant M16) differs from wild type at the amino-terminal end by a single altered residue at position three in the sequence. The observed change involves the substitution of an isoleucine in M16-R1 for a proline in wild type. This substitution requires a two-nucleotide change in the corresponding wild-type codon.--The combined genetic and biochemical data indicate that the qa-3 mutants M16 and M45 carry amino acid substitutions near the amino-terminal and carboxyl-terminal ends of the quinate dehydrogenase enzyme, respectively. On this basis we conclude that transcription of the qa-3 gene proceeds from the end specified by the M16 mutant site in the direction of the qa-1 gene. It appears probable that transcription is initiated from a promoter site within the qa cluster, possibly immediately adjacent to the qa-3 gene."} {"id": "PMID:159204", "title": "[Characteristics of bacteriophage lambda and P1 modification-restriction in Escherichia coli strains controlled by factor R124].", "content": "The specifities of restriction of bacteriophages P1 and lambda controlled by R plasmids in Escherichia coli have been investigated. The isogenic strains harbouring the plasmids pAS26 coding for restriction endonuclease R.EcoRI, R245 coding for restriction endonuclease R.EcoRII and and R124 have been investigated in the present work. Modification-restriction controlled by R124 has been found to differ in specificity from those controlled by R245 and pAS26. Frequencies of restriction of bacteriophages P1vir and lambdavir specified by R124 pasmid differ from the frequencies in the strains harbouring pAS26 and R245 plasmids as well. The difference is due to the specifity of restriction-modification controlled by R124 plasmid. The data obtained are consistent with the determination of R124 specified restriction-modification activity as a novel one designated R.EcoRIII.", "contents": "[Characteristics of bacteriophage lambda and P1 modification-restriction in Escherichia coli strains controlled by factor R124]. The specifities of restriction of bacteriophages P1 and lambda controlled by R plasmids in Escherichia coli have been investigated. The isogenic strains harbouring the plasmids pAS26 coding for restriction endonuclease R.EcoRI, R245 coding for restriction endonuclease R.EcoRII and and R124 have been investigated in the present work. Modification-restriction controlled by R124 has been found to differ in specificity from those controlled by R245 and pAS26. Frequencies of restriction of bacteriophages P1vir and lambdavir specified by R124 pasmid differ from the frequencies in the strains harbouring pAS26 and R245 plasmids as well. The difference is due to the specifity of restriction-modification controlled by R124 plasmid. The data obtained are consistent with the determination of R124 specified restriction-modification activity as a novel one designated R.EcoRIII."} {"id": "PMID:159206", "title": "Escherichia coli RNA polymerase binding and initiation of transcription on fragments of lambda rifd 18 DNA containing promoters for lambda genes and for rrnB, tufB, rplC,A, rplJ,L, and rpoB,C genes.", "content": "Promoters of genes for bacteriophage lambda and for Escherichia coli ribosomal RNA (rrnB), elongation factor Tu (tufB), ribosomal proteins L11 (rplK), L1 (rplA), L10 (rplJ), and L7/L12 (rplL), and RNA polymerase subunits beta (rpoB) and beta' (rpoC) were studied by use of two types of filter binding assays which measured E. coli RNA polymerase binding and initiation of transcription on restriction fragments of lambda rifd 18 DNA. The DNA fragments selectively retained on filters were eluted, concentrated, and analyzed by gel electrophoresis. The binding characteristics of these promotor fragments were qualitatively determined by varying the RNA polymerase, salt, and glycerol concentrations in the polymerase binding assay with HaeIII fragments of lambda rifd 18 DNA. The approximate map locations of these small HaeIII fragments were determined by HaeIII digestion of the larger, previously mapped EcoRI, HindIII, and SmaI restriction fragments of the phage DNA. The base compositions proximal to the 5' ends of mRNA's from promoters on these DNA fragments were elucidated by the polymerase initiation assay, in which the addition of various combinations of nucleoside triphosphates to the reaction allowed RNA polymerase to form high-salt-resistant initiation complexes with some of the known SmaI + EcoRI, EcoRI + HindIII, or HaeIII restriction fragments of lambda rifd 18 DNA. The data obtained by this technique are consistent with the map positions and 5' mRNA base sequences of the known lambda promotors p'R, po, pR and pL. In the main focus of this work, we have determined the approximate map locations and 5' mRNA base compositions of several promoters for known E. coli genes including rrnB, tufB, rplK,A, and rplJ,L. No promoter was detected between rplL and the rpoB,C genes. Thus our data are consistent with the conclusion of Yamamoto and Nomura (1978) that the beta and beta' mRNA is probably cotranscribed from the promoter for rplJ,L. Finally, the approximate map positions and the NTP combinations which initiated transcription of several unknown lambda and E. coli in vitro promoters are reported. The methods reported should prove useful for studying the characteristics of promoters on other cloned DNA regions.", "contents": "Escherichia coli RNA polymerase binding and initiation of transcription on fragments of lambda rifd 18 DNA containing promoters for lambda genes and for rrnB, tufB, rplC,A, rplJ,L, and rpoB,C genes. Promoters of genes for bacteriophage lambda and for Escherichia coli ribosomal RNA (rrnB), elongation factor Tu (tufB), ribosomal proteins L11 (rplK), L1 (rplA), L10 (rplJ), and L7/L12 (rplL), and RNA polymerase subunits beta (rpoB) and beta' (rpoC) were studied by use of two types of filter binding assays which measured E. coli RNA polymerase binding and initiation of transcription on restriction fragments of lambda rifd 18 DNA. The DNA fragments selectively retained on filters were eluted, concentrated, and analyzed by gel electrophoresis. The binding characteristics of these promotor fragments were qualitatively determined by varying the RNA polymerase, salt, and glycerol concentrations in the polymerase binding assay with HaeIII fragments of lambda rifd 18 DNA. The approximate map locations of these small HaeIII fragments were determined by HaeIII digestion of the larger, previously mapped EcoRI, HindIII, and SmaI restriction fragments of the phage DNA. The base compositions proximal to the 5' ends of mRNA's from promoters on these DNA fragments were elucidated by the polymerase initiation assay, in which the addition of various combinations of nucleoside triphosphates to the reaction allowed RNA polymerase to form high-salt-resistant initiation complexes with some of the known SmaI + EcoRI, EcoRI + HindIII, or HaeIII restriction fragments of lambda rifd 18 DNA. The data obtained by this technique are consistent with the map positions and 5' mRNA base sequences of the known lambda promotors p'R, po, pR and pL. In the main focus of this work, we have determined the approximate map locations and 5' mRNA base compositions of several promoters for known E. coli genes including rrnB, tufB, rplK,A, and rplJ,L. No promoter was detected between rplL and the rpoB,C genes. Thus our data are consistent with the conclusion of Yamamoto and Nomura (1978) that the beta and beta' mRNA is probably cotranscribed from the promoter for rplJ,L. Finally, the approximate map positions and the NTP combinations which initiated transcription of several unknown lambda and E. coli in vitro promoters are reported. The methods reported should prove useful for studying the characteristics of promoters on other cloned DNA regions."} {"id": "PMID:159207", "title": "Transfer of genome fragments in double infection of E. coli with T5 and phi X174 bacteriophages.", "content": "Double infection of Escherichia coli by two DNA phages (phi X174 and T5) resulted in encapsidation into T5 particles of T5 DNA containing linked fragments of phi X174 DNA. The phi X474 sequences in T5 \"hybrid\" DNA were detected by RNA-DNA hybridization.", "contents": "Transfer of genome fragments in double infection of E. coli with T5 and phi X174 bacteriophages. Double infection of Escherichia coli by two DNA phages (phi X174 and T5) resulted in encapsidation into T5 particles of T5 DNA containing linked fragments of phi X174 DNA. The phi X474 sequences in T5 \"hybrid\" DNA were detected by RNA-DNA hybridization."} {"id": "PMID:159209", "title": "Plasmid pKC7: a vector containing ten restriction endonuclease sites suitable for cloning DNA segments.", "content": "Plasmid pKC7, a derivative of pBR322, specifies resistance to both ampicillin and kanamycin. The DNA of this small plasmid (5.8 kb) contains unique sites for insertion of DNA cleaved with ten different restriction endonucleases. A detailed restriction endonuclease cleavage map is presented. The utility of this plasmid for cloning is discussed.", "contents": "Plasmid pKC7: a vector containing ten restriction endonuclease sites suitable for cloning DNA segments. Plasmid pKC7, a derivative of pBR322, specifies resistance to both ampicillin and kanamycin. The DNA of this small plasmid (5.8 kb) contains unique sites for insertion of DNA cleaved with ten different restriction endonucleases. A detailed restriction endonuclease cleavage map is presented. The utility of this plasmid for cloning is discussed."} {"id": "PMID:159223", "title": "[Clinical experience with mammography using grids (author's transl)].", "content": "Duplicate examinations were carried out on 122 patients in order to compare the results of mammography using a grid technique (Diagnost U. M\u00fcller) with a film-screen systemadn also a conventional set without screens (Mamma-Diagnost, M\u00fcller). The results were compared with reference to film quality and dose. The new technique was superior to the conventional method in all respects, independent of the size of the gland. Another advantage of the grid technique was the larger available film size. Dose requirements for grid mammography with a film-screen system was less than for conventional techniques by a factor of about 1.8. The results speak for increased use of the grid technique in clinical practice.", "contents": "[Clinical experience with mammography using grids (author's transl)]. Duplicate examinations were carried out on 122 patients in order to compare the results of mammography using a grid technique (Diagnost U. M\u00fcller) with a film-screen systemadn also a conventional set without screens (Mamma-Diagnost, M\u00fcller). The results were compared with reference to film quality and dose. The new technique was superior to the conventional method in all respects, independent of the size of the gland. Another advantage of the grid technique was the larger available film size. Dose requirements for grid mammography with a film-screen system was less than for conventional techniques by a factor of about 1.8. The results speak for increased use of the grid technique in clinical practice."} {"id": "PMID:159224", "title": "[Quantitative analysis as part of computer tomography of the skull (author's transl)].", "content": "The possibilities of quantitative evaluation of skull computer tomograms were explored in a group of 22 normals and compared with a group of 26 patients with cerebral tumours. Quantitative measurements of normal cerebral tissue and of tumours have revealed mean values for these groups which permit certain fundamental conclusions.", "contents": "[Quantitative analysis as part of computer tomography of the skull (author's transl)]. The possibilities of quantitative evaluation of skull computer tomograms were explored in a group of 22 normals and compared with a group of 26 patients with cerebral tumours. Quantitative measurements of normal cerebral tissue and of tumours have revealed mean values for these groups which permit certain fundamental conclusions."} {"id": "PMID:159225", "title": "[A comparison of cerebral angiography and computer tomography in patients with strokes (author's transl].", "content": "The computer tomographic findings in 230 patients with a clinical diagnosis of strokes or cerebral infarcts are described. In 185 of these patients cerebral angiography was performed in addition. The size and localisation of infarcts as shown on the computer tomogram were compared with the changes found in the carotid angiogram and were also related to the localisation of occlusion or stenosis of the corresponding extra- and intracranial vessels. In the presence of a normal carotid angiogram, CT may show infarcts of varying localisation and size; with stenoses or occlusion of the extracranial portion of the internal carotid artery, the infarcts tend to be smaller and that, in the presence of occulsions of the intracranial cerebral vessels, infarcts tend to be more extensive and to correspond to the territory supplied by the occluded vessels. Twenty-eight intracerebral haematomas and nine cerebral tumours were found amongst patients who presented as cerebral infarcts, with little evidence of massive cerebral bleeding; these are discussed separately.", "contents": "[A comparison of cerebral angiography and computer tomography in patients with strokes (author's transl]. The computer tomographic findings in 230 patients with a clinical diagnosis of strokes or cerebral infarcts are described. In 185 of these patients cerebral angiography was performed in addition. The size and localisation of infarcts as shown on the computer tomogram were compared with the changes found in the carotid angiogram and were also related to the localisation of occlusion or stenosis of the corresponding extra- and intracranial vessels. In the presence of a normal carotid angiogram, CT may show infarcts of varying localisation and size; with stenoses or occlusion of the extracranial portion of the internal carotid artery, the infarcts tend to be smaller and that, in the presence of occulsions of the intracranial cerebral vessels, infarcts tend to be more extensive and to correspond to the territory supplied by the occluded vessels. Twenty-eight intracerebral haematomas and nine cerebral tumours were found amongst patients who presented as cerebral infarcts, with little evidence of massive cerebral bleeding; these are discussed separately."} {"id": "PMID:159226", "title": "[The value of cranial computed tomography in posterior fossa epidermoids and dermoids (author's transl)].", "content": "Report on posterior fossa epidermoids and dermoids (3 in the cerebellopontine angle, 1 in the region of the fourth ventricle). Computed tomographic aspects are related with other neuroradiological findings. Differential diagnosis of these mass lesions is discussed in detail, especially of low density and (rarely occuring) high density epidermoids.", "contents": "[The value of cranial computed tomography in posterior fossa epidermoids and dermoids (author's transl)]. Report on posterior fossa epidermoids and dermoids (3 in the cerebellopontine angle, 1 in the region of the fourth ventricle). Computed tomographic aspects are related with other neuroradiological findings. Differential diagnosis of these mass lesions is discussed in detail, especially of low density and (rarely occuring) high density epidermoids."} {"id": "PMID:159227", "title": "[Computed tomography of soft tissue sarcomas (author's transl)].", "content": "CT findings in 50 patients with histologically verified soft tissue sarcomas are presented. In nearly all the cases the cross-sectional view and the higher resolution of density make it possible to determine exactly location of the tumors, their size and relationship to adjacent structures. Thus CT opens a new dimension, which is of great value for staging and therapy treatment planning. The high rank of CT in the follow-up after therapy and the detection of recurrent tumor is demonstrated. The contribution of CT, however, to the anatomic characteristics and its prospective value with the regard to soft tissue tumor is less important. Further limits of the method are discussed.", "contents": "[Computed tomography of soft tissue sarcomas (author's transl)]. CT findings in 50 patients with histologically verified soft tissue sarcomas are presented. In nearly all the cases the cross-sectional view and the higher resolution of density make it possible to determine exactly location of the tumors, their size and relationship to adjacent structures. Thus CT opens a new dimension, which is of great value for staging and therapy treatment planning. The high rank of CT in the follow-up after therapy and the detection of recurrent tumor is demonstrated. The contribution of CT, however, to the anatomic characteristics and its prospective value with the regard to soft tissue tumor is less important. Further limits of the method are discussed."} {"id": "PMID:159228", "title": "[Ultrasound diagnosis of renal stones (author's transl)].", "content": "Infusion urography and ultrasound examinations were performed in 54 patients in order to diagnose renal stones. The patients were examined because of upper abdominal pain, suspected renal calculi or for follow-up of known calculi. In 20 patients, stones could be demonstrated by both methods. In four patients, radiological suspicion of the presence of stones was not confirmed by ultrasound. In two patients ultrasound produced false positives and in seven patients renal stones were demonstrated only by sonography. These results were obtained with a mechanical sector scanner. The advantages and disadvantages of compound and of real-time-scanners and their place in the diagnosis of kidney stones are discussed.", "contents": "[Ultrasound diagnosis of renal stones (author's transl)]. Infusion urography and ultrasound examinations were performed in 54 patients in order to diagnose renal stones. The patients were examined because of upper abdominal pain, suspected renal calculi or for follow-up of known calculi. In 20 patients, stones could be demonstrated by both methods. In four patients, radiological suspicion of the presence of stones was not confirmed by ultrasound. In two patients ultrasound produced false positives and in seven patients renal stones were demonstrated only by sonography. These results were obtained with a mechanical sector scanner. The advantages and disadvantages of compound and of real-time-scanners and their place in the diagnosis of kidney stones are discussed."} {"id": "PMID:159229", "title": "[Sonography and angiography in the investigation of space-occupying lesions of the kidney (author's transl)].", "content": "The results of angiography and sonography in 132 patients suspected of having a space-occuping lesion in a kidney were compared; they were examined by excretion urography, ultrasound and renal angiography. All lesions demonstrated angiographically had already been seen by ultrasound. Difficulties were experienced with cysts of less than 3 cm. Diameter situated in the region of the hilum, which did not always produce echo-free images. Infected renal cysts appeared as avascular space-occupying lesions on angiography, but showed echoes on sonography.", "contents": "[Sonography and angiography in the investigation of space-occupying lesions of the kidney (author's transl)]. The results of angiography and sonography in 132 patients suspected of having a space-occuping lesion in a kidney were compared; they were examined by excretion urography, ultrasound and renal angiography. All lesions demonstrated angiographically had already been seen by ultrasound. Difficulties were experienced with cysts of less than 3 cm. Diameter situated in the region of the hilum, which did not always produce echo-free images. Infected renal cysts appeared as avascular space-occupying lesions on angiography, but showed echoes on sonography."} {"id": "PMID:159230", "title": "[Acute renal vein thrombosis in infancy (author's transl)].", "content": "Two cases of acute renal vein thrombosis are presented. Instead of angiography, sonography was used to perform the diagnosis. After short discription of the etiology, clinic and roentgensymptomatology, the sonographic semiology is emphasized. In the discussion the sonographic differentialdiagnosis is reviewed and the possible therapeutic proceedings are mentioned. The value of sonography as non-invasive method, especially in newborn is therefore established.", "contents": "[Acute renal vein thrombosis in infancy (author's transl)]. Two cases of acute renal vein thrombosis are presented. Instead of angiography, sonography was used to perform the diagnosis. After short discription of the etiology, clinic and roentgensymptomatology, the sonographic semiology is emphasized. In the discussion the sonographic differentialdiagnosis is reviewed and the possible therapeutic proceedings are mentioned. The value of sonography as non-invasive method, especially in newborn is therefore established."} {"id": "PMID:159231", "title": "[Sonography and pharmacoangiography of the pancreas (author's transl)].", "content": "Real-Time-Sonography and pharmacoangiography with vasodilating drugs was performed in 63 patients with suspected pancreatic disease. Confirmation of the pancreatic lesion could be obtained in 41 cases by the symptomatology, pancreatic function test, autopsy, operation, laparoscopy with fine-needle-biopsy and by the roentgenologic visualization of pancreatic calcifications. Considering the relatively advanced disease of pancreatic carcinoma in our six patients the sonographic diagnosis was correct in all of them and with pharmacoangiography we failed on one case. In chronic pancreatitis correct diagnostic results with pharmacoangiography could be obtained in 8 of 18 cases and with sonography in 14 of 18 patients. In this study sonography showed certain advantages in comparison with angiography, but both methods were complementary and a better result in the differential diagnosis between chronic pancreatitis and pancreatic carcinoma could be achieved.", "contents": "[Sonography and pharmacoangiography of the pancreas (author's transl)]. Real-Time-Sonography and pharmacoangiography with vasodilating drugs was performed in 63 patients with suspected pancreatic disease. Confirmation of the pancreatic lesion could be obtained in 41 cases by the symptomatology, pancreatic function test, autopsy, operation, laparoscopy with fine-needle-biopsy and by the roentgenologic visualization of pancreatic calcifications. Considering the relatively advanced disease of pancreatic carcinoma in our six patients the sonographic diagnosis was correct in all of them and with pharmacoangiography we failed on one case. In chronic pancreatitis correct diagnostic results with pharmacoangiography could be obtained in 8 of 18 cases and with sonography in 14 of 18 patients. In this study sonography showed certain advantages in comparison with angiography, but both methods were complementary and a better result in the differential diagnosis between chronic pancreatitis and pancreatic carcinoma could be achieved."} {"id": "PMID:159232", "title": "[Hemorrhage through the pancreatic duct -- endoscopic-radiological diagnosis (author's transl)].", "content": "Hemobilia and pancreatic hemorrhage must be considered in the differential diagnosis of bleeding fromthe papilla Vateri. Retrograde pancreaticography and angiography are the essentials of the further diagnostic workup. Both methods together can reveal the origin and localization of the bleeding.", "contents": "[Hemorrhage through the pancreatic duct -- endoscopic-radiological diagnosis (author's transl)]. Hemobilia and pancreatic hemorrhage must be considered in the differential diagnosis of bleeding fromthe papilla Vateri. Retrograde pancreaticography and angiography are the essentials of the further diagnostic workup. Both methods together can reveal the origin and localization of the bleeding."} {"id": "PMID:159233", "title": "[Phlebography for pre- and posttherapeutic control of fibrinolysis and thrombectomy (author's transl)].", "content": "The indications for fibrinolysis or thrombectomy when there is suspected fresh ilio-femoral venous thrombosis should be based on accurate phlebography at the earliest possible moment. Early posttherapeutic phlebography under standardised conditions should be used to control further treatment. Later examinations document the final outcome. Early phlebography, when treatment has been discontinued and has been unsuccessful, shows the so-called \"Rischhalte phenomenon\", which may be an indication for further thrombectomy. Seven cases are reported in which primary fibrinolysis with streptokinase was followed by thrombectomy with a Fogarty catheter. 3-Step-phlebography provides the essential information which governs treatment and demonstrates its results.", "contents": "[Phlebography for pre- and posttherapeutic control of fibrinolysis and thrombectomy (author's transl)]. The indications for fibrinolysis or thrombectomy when there is suspected fresh ilio-femoral venous thrombosis should be based on accurate phlebography at the earliest possible moment. Early posttherapeutic phlebography under standardised conditions should be used to control further treatment. Later examinations document the final outcome. Early phlebography, when treatment has been discontinued and has been unsuccessful, shows the so-called \"Rischhalte phenomenon\", which may be an indication for further thrombectomy. Seven cases are reported in which primary fibrinolysis with streptokinase was followed by thrombectomy with a Fogarty catheter. 3-Step-phlebography provides the essential information which governs treatment and demonstrates its results."} {"id": "PMID:159234", "title": "[Isotope methods in the radiological diagnosis of venous disease. II. Indications and accuracy (author's transl)].", "content": "Radiological diagnostic methods for the diagnosis of abnormalities of veins were discussed in the light of 1,683 contrast venograms and isotope examinations in 650 patients with acute and chronic diseases of veins. For patients with increased thrombotic risks, the 125 I-fibrinogen test is recommended as a sensitive and simple method. Where there are symptoms of venous thrombosis, radionuclide venography, together with other noninvasive methods, may be used for establishing whether there are indications for contrast venography. These may also provide evidence of previous pulmonary emboli. These methods should also be used where there is clinical suspicion of previous pulmonary emboli. Non-invasive isotope methods have proved to be sensitive techniques for preliminary examinations and for follow-up. Contrast venography is necessary if definitive treatment is planned.", "contents": "[Isotope methods in the radiological diagnosis of venous disease. II. Indications and accuracy (author's transl)]. Radiological diagnostic methods for the diagnosis of abnormalities of veins were discussed in the light of 1,683 contrast venograms and isotope examinations in 650 patients with acute and chronic diseases of veins. For patients with increased thrombotic risks, the 125 I-fibrinogen test is recommended as a sensitive and simple method. Where there are symptoms of venous thrombosis, radionuclide venography, together with other noninvasive methods, may be used for establishing whether there are indications for contrast venography. These may also provide evidence of previous pulmonary emboli. These methods should also be used where there is clinical suspicion of previous pulmonary emboli. Non-invasive isotope methods have proved to be sensitive techniques for preliminary examinations and for follow-up. Contrast venography is necessary if definitive treatment is planned."} {"id": "PMID:159235", "title": "[Radio-nuclide phlebography: methods, indications and clinical value (author's transl)].", "content": "Radionuclide venography (RNV) is an easily performed, rapid and non-invasive diagnostic examination for the detection of deep-vein thrombosis. Provided the procedure is followed out in a standardized order, the results are highly reliable and accurate, especially in the iliac and femoral veins. Therefore, because of this advantage and the possibility of simultaneous lung perfusion scanning and the lack of serious complications this method fills a gap between contrast phlebography and fibrinogen test. 122 limbs of 69 patients were investigated by RNS. 65% showed pathologic results. In 48% thrombotic venous occlusions could be demonstrated. Pulmonary embolic perfusion defects were found in 46% of patients presenting deep vein thrombosis but only in 15% of patients without pathologic findings in RNV. In correlation with contrast phlebography in 11 patients there was no discrepancy neither in recognition nor in localization of the thrombotic occlusion. The essential findings in RNV and the resulting diagnostic conclusions are demonstrated.", "contents": "[Radio-nuclide phlebography: methods, indications and clinical value (author's transl)]. Radionuclide venography (RNV) is an easily performed, rapid and non-invasive diagnostic examination for the detection of deep-vein thrombosis. Provided the procedure is followed out in a standardized order, the results are highly reliable and accurate, especially in the iliac and femoral veins. Therefore, because of this advantage and the possibility of simultaneous lung perfusion scanning and the lack of serious complications this method fills a gap between contrast phlebography and fibrinogen test. 122 limbs of 69 patients were investigated by RNS. 65% showed pathologic results. In 48% thrombotic venous occlusions could be demonstrated. Pulmonary embolic perfusion defects were found in 46% of patients presenting deep vein thrombosis but only in 15% of patients without pathologic findings in RNV. In correlation with contrast phlebography in 11 patients there was no discrepancy neither in recognition nor in localization of the thrombotic occlusion. The essential findings in RNV and the resulting diagnostic conclusions are demonstrated."} {"id": "PMID:159236", "title": "[Changes in the cervical spine in juvenile rheumatoid arthritis (author's transl)].", "content": "Changes in the cervical spine in juvenile rheumatoid arthritis can be shown by A.P., lateral and functional views with maximal flexion and extension, and particularly by tomography. The latter is essential for proper evaluation of the atlanto-occipital and atlanto-axial joints and of the odontoid. Atlanto-axial subluxation was found in eight out of eighty-four patients. Destruction of the odontoid was found in twelve out of fifty-three patients examined by tomography. The earliest tomographic changes at the atlanto-occipital joint consists of isolated joint narrowing, erosions and fusion and were observed in sixty-four out of sixty-six patients examined. Similar findings at the atlanto-axial joint were observed in thirty-seven out of sixty-six cases. The severity of the changes correlated with seropositivity and duration of the disease. The most marked changes were found with a prolonged history and a positive Rose-Waaler reaction.", "contents": "[Changes in the cervical spine in juvenile rheumatoid arthritis (author's transl)]. Changes in the cervical spine in juvenile rheumatoid arthritis can be shown by A.P., lateral and functional views with maximal flexion and extension, and particularly by tomography. The latter is essential for proper evaluation of the atlanto-occipital and atlanto-axial joints and of the odontoid. Atlanto-axial subluxation was found in eight out of eighty-four patients. Destruction of the odontoid was found in twelve out of fifty-three patients examined by tomography. The earliest tomographic changes at the atlanto-occipital joint consists of isolated joint narrowing, erosions and fusion and were observed in sixty-four out of sixty-six patients examined. Similar findings at the atlanto-axial joint were observed in thirty-seven out of sixty-six cases. The severity of the changes correlated with seropositivity and duration of the disease. The most marked changes were found with a prolonged history and a positive Rose-Waaler reaction."} {"id": "PMID:159237", "title": "[The radiological appearances of the normal joint spaces in the hand (author's transl)].", "content": "The radio-carpal joints in 120 normal persons were examined by arthrography. It was shown that this joint communicates with the carpal joints, carpo-metacarpal joints and with the distal radio-ulnar joint. Three types, with various accessory pouches, could be defined. A study of the normal radiological anatomy of the radio-carpal joint is necessary before a diagnosis of pathological changes in the joint can be made.", "contents": "[The radiological appearances of the normal joint spaces in the hand (author's transl)]. The radio-carpal joints in 120 normal persons were examined by arthrography. It was shown that this joint communicates with the carpal joints, carpo-metacarpal joints and with the distal radio-ulnar joint. Three types, with various accessory pouches, could be defined. A study of the normal radiological anatomy of the radio-carpal joint is necessary before a diagnosis of pathological changes in the joint can be made."} {"id": "PMID:159246", "title": "[Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid].", "content": "The side effects and possible side effects of the therapy with valproic acid were documented in 66 outpatients with epilepsy over a period of one year. The serum levels of valproic acid were measured gaschromatographically over the same period. The majority of the patients received a combined medication. The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients. Patients complaining of tiredness showed significantly higher serum valproic acid levels than patients without clinical side effects. The other comparisons between the serum valproic acid levels in the case of clinical side effects and changes in laboratory findings and the serum levels of patients without side effects or changes in laboratory findings did not indicate a definite difference.", "contents": "[Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid]. The side effects and possible side effects of the therapy with valproic acid were documented in 66 outpatients with epilepsy over a period of one year. The serum levels of valproic acid were measured gaschromatographically over the same period. The majority of the patients received a combined medication. The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients. Patients complaining of tiredness showed significantly higher serum valproic acid levels than patients without clinical side effects. The other comparisons between the serum valproic acid levels in the case of clinical side effects and changes in laboratory findings and the serum levels of patients without side effects or changes in laboratory findings did not indicate a definite difference."} {"id": "PMID:159247", "title": "[Plastic surgery in mongoloid children].", "content": "The aim of plastic surgery in children with Down-syndrome is the improvement of speech as well as improvement of cosmetic appearance. Altering the typical mongoloid physiognomy facilitates the integration of these children into the community. In our Department during the past 6 months plastic surgery was performed in 27 children for the correction of macroglossia, saddle nose deformity, epicanthic folds, receding chin, fatty neck and deformity of the ears. Macroglossia was present in every case, the extent of further surgery varies according to the clinical deformity. It is essential to discuss the implications of surgery in these children with the parents in order to avoid later disappointment.", "contents": "[Plastic surgery in mongoloid children]. The aim of plastic surgery in children with Down-syndrome is the improvement of speech as well as improvement of cosmetic appearance. Altering the typical mongoloid physiognomy facilitates the integration of these children into the community. In our Department during the past 6 months plastic surgery was performed in 27 children for the correction of macroglossia, saddle nose deformity, epicanthic folds, receding chin, fatty neck and deformity of the ears. Macroglossia was present in every case, the extent of further surgery varies according to the clinical deformity. It is essential to discuss the implications of surgery in these children with the parents in order to avoid later disappointment."} {"id": "PMID:159249", "title": "[Sodium fluoride in the therapy of osteoporosis].", "content": "Every form of osteoporosis--except the physiological involution osteoporosis--requires treatment. Osteoporosis is no disease by itself but a result or a concomitant phenomenon of various diseases. Therefore the primary disease has to be treated also. Only for the so-called idiopathic osteoporosis hitherto no cause is known. Today sodium fluoride is the only substance with an influence upon the bone which may induce re-ossification and re-stabilization. In the described series of investigations this compound, with which treatment by gradual dosage is possible, has proved its effectiveness. Osteoporosis is more than bone porosity, therefore additionally afflicted organic or functional system like the muscular apparatus, bone marrow, or the intraosseous blood supply, must be treated too. Psychological guidance of the patient is necessary as he must be motivated for activity.", "contents": "[Sodium fluoride in the therapy of osteoporosis]. Every form of osteoporosis--except the physiological involution osteoporosis--requires treatment. Osteoporosis is no disease by itself but a result or a concomitant phenomenon of various diseases. Therefore the primary disease has to be treated also. Only for the so-called idiopathic osteoporosis hitherto no cause is known. Today sodium fluoride is the only substance with an influence upon the bone which may induce re-ossification and re-stabilization. In the described series of investigations this compound, with which treatment by gradual dosage is possible, has proved its effectiveness. Osteoporosis is more than bone porosity, therefore additionally afflicted organic or functional system like the muscular apparatus, bone marrow, or the intraosseous blood supply, must be treated too. Psychological guidance of the patient is necessary as he must be motivated for activity."} {"id": "PMID:159250", "title": "Nicotinamide modulation of rat pancreatic islet cell responsiveness in vitro.", "content": "The influence of nicotinamide (NA), a highly suitable precursor substrate for NAD synthesis in various tissues, on islet cell responsiveness was determined. After a 30 minute perifusion with this compound, nicotinamide, in a dose-dependent manner, potentiated glucose-induced insulin secretion. Maximal potentiation (approximately 250%) was observed at 20 mM NA and the threshold for potentiation was 3 mM. In the absence of glucose, NA did not affect basal secretion rates. Mannoheptulose blocked the primary stimulant action of glucose and the potentiating effects of NA. NA did not alter the rate of glucose usage by isolated islets. These results further underscore the possible importance of pyridine nucleotides in stimulated secretion.", "contents": "Nicotinamide modulation of rat pancreatic islet cell responsiveness in vitro. The influence of nicotinamide (NA), a highly suitable precursor substrate for NAD synthesis in various tissues, on islet cell responsiveness was determined. After a 30 minute perifusion with this compound, nicotinamide, in a dose-dependent manner, potentiated glucose-induced insulin secretion. Maximal potentiation (approximately 250%) was observed at 20 mM NA and the threshold for potentiation was 3 mM. In the absence of glucose, NA did not affect basal secretion rates. Mannoheptulose blocked the primary stimulant action of glucose and the potentiating effects of NA. NA did not alter the rate of glucose usage by isolated islets. These results further underscore the possible importance of pyridine nucleotides in stimulated secretion."} {"id": "PMID:159251", "title": "Substrate specificity of a heparan sulfate-degrading endoglucuronidase from human placenta.", "content": "A heparan sulfate-degrading endoglucuronidase was isolated from human placenta and partially purified by affinity chromatography on heparan sulfate-Sepharose 4B. The endoglucuronidase has a molecular weight of approximately 100 000 estimated by gel chromatography and a broad pH optimum between pH4 and pH6. Carboxyl reduced heparan sulfate is not split by partially purified endoglucuronidase, but inhibits the action of that enzyme towards non-modified heparan sulfate. Low molecular weight heparan sulfate (Mr approximately 3 000) is not attacked by the endoglucuronidase. N-Desulfated heparan sulfate and heparin are only weak substrates. The amino sugar adjacent to the glucuronic acid residue appearing at the reducing terminal of heparan sulfate fragments liberated by the endoglucuronidase appears to be exclusively N-acetylated glucosamine.", "contents": "Substrate specificity of a heparan sulfate-degrading endoglucuronidase from human placenta. A heparan sulfate-degrading endoglucuronidase was isolated from human placenta and partially purified by affinity chromatography on heparan sulfate-Sepharose 4B. The endoglucuronidase has a molecular weight of approximately 100 000 estimated by gel chromatography and a broad pH optimum between pH4 and pH6. Carboxyl reduced heparan sulfate is not split by partially purified endoglucuronidase, but inhibits the action of that enzyme towards non-modified heparan sulfate. Low molecular weight heparan sulfate (Mr approximately 3 000) is not attacked by the endoglucuronidase. N-Desulfated heparan sulfate and heparin are only weak substrates. The amino sugar adjacent to the glucuronic acid residue appearing at the reducing terminal of heparan sulfate fragments liberated by the endoglucuronidase appears to be exclusively N-acetylated glucosamine."} {"id": "PMID:159255", "title": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. XIII. The identity of the responder cells and the role of phagocytic cells in the mixed leucocyte culture reaction.", "content": "The ability of rabbit spleen cells depleted of thymus, bone marrow or appendix-derived cells to respond in the one-way mixed leucocyte reaction (MLR) has been investigated. The specific subpopulations of lymphoid cells were eliminated by lysis of these cells in the presence of specific antisera and complement. Phagocytic cells (monocytes and heterophils) were removed with a strong magnet after incubation with carbonyl iron particles. The results indicate that the MLR-responding cells are thymus-derived and that neither bone marrow-derived cells nor appendix-derived cells are essential for the blastogenic response following stimulation with allogeneic cells. A minimum number of phagocytic cells is required for a significant response. These cells, however, exhibit a non-specific (accessory) role and can be supplied by either the responding or the stimulating cell population.", "contents": "The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. XIII. The identity of the responder cells and the role of phagocytic cells in the mixed leucocyte culture reaction. The ability of rabbit spleen cells depleted of thymus, bone marrow or appendix-derived cells to respond in the one-way mixed leucocyte reaction (MLR) has been investigated. The specific subpopulations of lymphoid cells were eliminated by lysis of these cells in the presence of specific antisera and complement. Phagocytic cells (monocytes and heterophils) were removed with a strong magnet after incubation with carbonyl iron particles. The results indicate that the MLR-responding cells are thymus-derived and that neither bone marrow-derived cells nor appendix-derived cells are essential for the blastogenic response following stimulation with allogeneic cells. A minimum number of phagocytic cells is required for a significant response. These cells, however, exhibit a non-specific (accessory) role and can be supplied by either the responding or the stimulating cell population."} {"id": "PMID:159254", "title": "The Papillon-Lef\u00e8vre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature.", "content": "The Papillon-Lef\u00e9vre syndrome (PLS) is an autosomal recessive trait characterized by diffuse transgredient palmar-plantar keratosis (PPK) and premature loss of both the deciduous and permanent teeth. In most cases, the PPK is noted within the first 3 years of life. The periodontal lesions begin shortly after the start of both the primary and the permanent dentitions. The teeth are affected in the order of their eruption, exhibiting inflammation of the periodontal tissue, bleeding of the gums, pocket formation, loosening, and finally spontaneous exfoliation without showing definite signs of root resorption. After an edentulous interval, the same process begins anew shortly after the second dentition. Ectopic intracranial calcifications, mental retardation, and increased susceptibility to infections have often been seen in PLS patients and may thus be regarded as facultative signs.", "contents": "The Papillon-Lef\u00e8vre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature. The Papillon-Lef\u00e9vre syndrome (PLS) is an autosomal recessive trait characterized by diffuse transgredient palmar-plantar keratosis (PPK) and premature loss of both the deciduous and permanent teeth. In most cases, the PPK is noted within the first 3 years of life. The periodontal lesions begin shortly after the start of both the primary and the permanent dentitions. The teeth are affected in the order of their eruption, exhibiting inflammation of the periodontal tissue, bleeding of the gums, pocket formation, loosening, and finally spontaneous exfoliation without showing definite signs of root resorption. After an edentulous interval, the same process begins anew shortly after the second dentition. Ectopic intracranial calcifications, mental retardation, and increased susceptibility to infections have often been seen in PLS patients and may thus be regarded as facultative signs."} {"id": "PMID:159256", "title": "Comparative patterns of serum immunoglobulin levels in specific-pathogen-free congenitally athymic (nude), hereditarily asplenic (Dh/+), congenitally athymic-asplenic (lasat) and splenectomized athymic mice.", "content": "Serial determinations of serum immunoglobulin levels were assessed in congenitally athymic (nude), hereditarily asplenic (Dh/+) and congenitally athymic-asplenic (lasat) mice and the results compared to normal intact littermate controls (nu/+), neonatally splenectomized nu/+ and neonatally splenectomized nude mice. Quantification of Ig levels was accomplished by radial immunodiffusion, for IgM, IgG1, IgG2a, IgG2b and IgA antibody isotypes. Intact spleen and/or thymus function was shown to have marked effects on the age-dependent development of serum IgM, IgG2b and IgA production. Furthermore, because of higher levels of IgA in congenitally athymic-asplenic mice and neonatally splenectomized nude mice v. sham splenectomized nude mice, it is suggested that an IgA-specific suppressor population resides in the spleen. Finally, because of frequent problems in the literature in interpretation of immunoglobulin values, the criteria for the statistical evaluation of such data in establishing normal serum Ig values and ascertaining real differences between treatment groups are emphasized.", "contents": "Comparative patterns of serum immunoglobulin levels in specific-pathogen-free congenitally athymic (nude), hereditarily asplenic (Dh/+), congenitally athymic-asplenic (lasat) and splenectomized athymic mice. Serial determinations of serum immunoglobulin levels were assessed in congenitally athymic (nude), hereditarily asplenic (Dh/+) and congenitally athymic-asplenic (lasat) mice and the results compared to normal intact littermate controls (nu/+), neonatally splenectomized nu/+ and neonatally splenectomized nude mice. Quantification of Ig levels was accomplished by radial immunodiffusion, for IgM, IgG1, IgG2a, IgG2b and IgA antibody isotypes. Intact spleen and/or thymus function was shown to have marked effects on the age-dependent development of serum IgM, IgG2b and IgA production. Furthermore, because of higher levels of IgA in congenitally athymic-asplenic mice and neonatally splenectomized nude mice v. sham splenectomized nude mice, it is suggested that an IgA-specific suppressor population resides in the spleen. Finally, because of frequent problems in the literature in interpretation of immunoglobulin values, the criteria for the statistical evaluation of such data in establishing normal serum Ig values and ascertaining real differences between treatment groups are emphasized."} {"id": "PMID:159259", "title": "Effect of visceral leishmaniasis on congenitally athymic mice.", "content": "Congenitally athymic mice were more susceptible to challenge with amastigotes of Leishmania donovani than were their thymus-intact littermates. This increased susceptibility correlated with a lack of Arthus and delayed-type responses when animals were skin tested with leishmanial antigen.", "contents": "Effect of visceral leishmaniasis on congenitally athymic mice. Congenitally athymic mice were more susceptible to challenge with amastigotes of Leishmania donovani than were their thymus-intact littermates. This increased susceptibility correlated with a lack of Arthus and delayed-type responses when animals were skin tested with leishmanial antigen."} {"id": "PMID:159260", "title": "Inhibition of translocation of viable Escherichia coli from the gastrointestinal tract of mice by bacterial antagonism.", "content": "The incidence of translocation of viable Escherichia coli C25 from the gastrointestinal tract to the mesenteric lymph nodes was compared in gnotobiotic mice colonized with only E. coli C25 and in gnotobiotic mice colonized with E. coli C25 plus the whole cecal flora from specific pathogen-free mice. The population levels of E. coli C25 in the ilea and ceca of these mice also were compared. E. coli C25 maintained high population levels in the gastrointestinal tracts of the monoassociated gnotobiotes, and the incidence of translocation to the mesenteric lymph nodes was 100%. The gastrointestinal population levels of E. coli C25 were reduced drastically in the gnotobiotes associated with both E. coli C25 and a cecal flora with concomitant reduction in the incidence of translocation of E. coli C25 from 100 to 0%. A decrease in the numbers of viable E. coli C25 per mesenteric lymph node also accompanied the decrease in C. coli C25 population levels in the gastrointestinal tracts of these mice. Thus, high population levels of E. coli C25 in the gastrointestinal tracts of monoassociated gnotobiotic mice appear to promote translocation of viable E. coli C25 to the mesenteric lymph nodes. Bacterial antagonism of E. coli population levels in conventional mice, therefore, could be one mechanism whereby viable E. coli are confined to the gastrointestinal tract.", "contents": "Inhibition of translocation of viable Escherichia coli from the gastrointestinal tract of mice by bacterial antagonism. The incidence of translocation of viable Escherichia coli C25 from the gastrointestinal tract to the mesenteric lymph nodes was compared in gnotobiotic mice colonized with only E. coli C25 and in gnotobiotic mice colonized with E. coli C25 plus the whole cecal flora from specific pathogen-free mice. The population levels of E. coli C25 in the ilea and ceca of these mice also were compared. E. coli C25 maintained high population levels in the gastrointestinal tracts of the monoassociated gnotobiotes, and the incidence of translocation to the mesenteric lymph nodes was 100%. The gastrointestinal population levels of E. coli C25 were reduced drastically in the gnotobiotes associated with both E. coli C25 and a cecal flora with concomitant reduction in the incidence of translocation of E. coli C25 from 100 to 0%. A decrease in the numbers of viable E. coli C25 per mesenteric lymph node also accompanied the decrease in C. coli C25 population levels in the gastrointestinal tracts of these mice. Thus, high population levels of E. coli C25 in the gastrointestinal tracts of monoassociated gnotobiotic mice appear to promote translocation of viable E. coli C25 to the mesenteric lymph nodes. Bacterial antagonism of E. coli population levels in conventional mice, therefore, could be one mechanism whereby viable E. coli are confined to the gastrointestinal tract."} {"id": "PMID:159261", "title": "Complement activation in acne vulgaris: consumption of complement by comedones.", "content": "Comedones, the contents of acne lesions, were shown to consume scomplement hemolytic activity in normal serum. This consumption was stimulated by the addition of serum from patients with inflammatory acne. Absorption of acne serum with Propionibacterium acnes cells removed all stimulating activity. Immunoelectrophoretic analysis of serum incubated with comedones revealed the conversion of C3 and factor B in normal serum. The addition of acne serum resulted in cleavage of C4. In serum treated with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, only C3 and factor B were converted. This indicates that comedones may activate complement by either the classical or the alternative pathway. It is suggested that P. acnes cells in comedonal material are responsible for the complement activation.", "contents": "Complement activation in acne vulgaris: consumption of complement by comedones. Comedones, the contents of acne lesions, were shown to consume scomplement hemolytic activity in normal serum. This consumption was stimulated by the addition of serum from patients with inflammatory acne. Absorption of acne serum with Propionibacterium acnes cells removed all stimulating activity. Immunoelectrophoretic analysis of serum incubated with comedones revealed the conversion of C3 and factor B in normal serum. The addition of acne serum resulted in cleavage of C4. In serum treated with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, only C3 and factor B were converted. This indicates that comedones may activate complement by either the classical or the alternative pathway. It is suggested that P. acnes cells in comedonal material are responsible for the complement activation."} {"id": "PMID:159263", "title": "Depression of contact sensitivity by Pseudomonas aeruginosa-induced suppressor cells which affect the induction phase of immune response.", "content": "The cellular basis of depression of contact sensitivity to oxazolone in mice injected with Pseudomonas aeruginosa was studied. Cells from draining lymph nodes of mice sensitized with oxazolone 18 h previously were able to induce contact sensitivity to normal mice when administered in their footpads. In contrast, cells from draining lymph nodes of P. aeruginosa-injected and oxazolone-sensitized donors failed to induce contact sensitivity when injected in the footpad of normal mice and were capable of actively blocking the immunizing process brought about by lymph node cells from sensitized mice when injected together in the footpad of normal recipients. The P. aeruginosa-induced suppressor cells required antigenic stimulation, had precursors sensitive to cyclophosphamide, and did not affect the effector mechanisms of contact sensitivity. Thus, the results suggest that P. aeurginosa depresses contact sensitivity to oxazolone by enhancing the activity of suppressor cells which normally arise during the sensitization process and which affect the afferent limb of the immune response, probably by inhibiting the normal recruitment of T lymphocytes in the draining lymph nodes.", "contents": "Depression of contact sensitivity by Pseudomonas aeruginosa-induced suppressor cells which affect the induction phase of immune response. The cellular basis of depression of contact sensitivity to oxazolone in mice injected with Pseudomonas aeruginosa was studied. Cells from draining lymph nodes of mice sensitized with oxazolone 18 h previously were able to induce contact sensitivity to normal mice when administered in their footpads. In contrast, cells from draining lymph nodes of P. aeruginosa-injected and oxazolone-sensitized donors failed to induce contact sensitivity when injected in the footpad of normal mice and were capable of actively blocking the immunizing process brought about by lymph node cells from sensitized mice when injected together in the footpad of normal recipients. The P. aeruginosa-induced suppressor cells required antigenic stimulation, had precursors sensitive to cyclophosphamide, and did not affect the effector mechanisms of contact sensitivity. Thus, the results suggest that P. aeurginosa depresses contact sensitivity to oxazolone by enhancing the activity of suppressor cells which normally arise during the sensitization process and which affect the afferent limb of the immune response, probably by inhibiting the normal recruitment of T lymphocytes in the draining lymph nodes."} {"id": "PMID:159262", "title": "Role of environment in the development of \"natural\" hemagglutinins in Minnesota miniature swine.", "content": "\"Natural\" hemagglutinin titers against a panel of fixed erythrocyte antigens were determined for groups of Minnesota miniature swine reared conventionally, in a specific pathogen-free facility, and in germfree isolators. Sera were assayed for hemagglutination (HA) titers by the microtiter method against 12 species of erythrocytes stabilized by treatment with pyruvic aldehyde and formaldehyde. These erythrocytes were stable for up to 2 years and gave slightly enhanced HA titers as compared to fresh, unfixed erythrocytes. Of the sera from conventional swine tested, the highest \"natural\" HA titers were directed towards rabbit, cat, swine dog, and burro erythrocytes (greater than 1:1,000), intermediate titers were detected against human A, B, and O, and sheep, pig, and chicken erythrocytes (1:64 to 1:1,000), whereas the lowest titers were found against ox and goat erythrocytes (less than 1:8). Titers obtained with sera from specific pathogen-free swine were 2- to 16-fold lower than those of conventional swine, but were of a similar distribution with regard to the species of erythrocyte tested. Germfree swine sera uniformly exhibited HA titers less than 1:4 against all species of erythrocytes. The majority of these hemagglutinins were immunoglobulin M class but there were some agglutinins of immunoglobulin A class and a slight amount of immunoglobulin G class. Specificity of these agglutinins was examined by absorption tests. The results are consistent with the hypothesis that natural hemagglutinins develop due to dietary or microbial antigenic stimulation, or both.", "contents": "Role of environment in the development of \"natural\" hemagglutinins in Minnesota miniature swine. \"Natural\" hemagglutinin titers against a panel of fixed erythrocyte antigens were determined for groups of Minnesota miniature swine reared conventionally, in a specific pathogen-free facility, and in germfree isolators. Sera were assayed for hemagglutination (HA) titers by the microtiter method against 12 species of erythrocytes stabilized by treatment with pyruvic aldehyde and formaldehyde. These erythrocytes were stable for up to 2 years and gave slightly enhanced HA titers as compared to fresh, unfixed erythrocytes. Of the sera from conventional swine tested, the highest \"natural\" HA titers were directed towards rabbit, cat, swine dog, and burro erythrocytes (greater than 1:1,000), intermediate titers were detected against human A, B, and O, and sheep, pig, and chicken erythrocytes (1:64 to 1:1,000), whereas the lowest titers were found against ox and goat erythrocytes (less than 1:8). Titers obtained with sera from specific pathogen-free swine were 2- to 16-fold lower than those of conventional swine, but were of a similar distribution with regard to the species of erythrocyte tested. Germfree swine sera uniformly exhibited HA titers less than 1:4 against all species of erythrocytes. The majority of these hemagglutinins were immunoglobulin M class but there were some agglutinins of immunoglobulin A class and a slight amount of immunoglobulin G class. Specificity of these agglutinins was examined by absorption tests. The results are consistent with the hypothesis that natural hemagglutinins develop due to dietary or microbial antigenic stimulation, or both."} {"id": "PMID:159264", "title": "Suppression of lymphocyte response to concanavalin A by mucopolysaccharide material from Treponema pallidum-infected rabbits.", "content": "The testicular fluid and serum from rabbits infected intratesticularly with Treponema pallidum inhibited the mitogenic response of normal rabbit peripheral blood lymphocytes to concanavalin A. Mucopolysaccharide material present in the testicular fluid and serum was associated with the lymphocyte-inhibitory activity. Degradation of the mucopolysaccharide material with hyaluronidase resulted in the loss of the inhibitory activity of testicular fluid and serum of T. pallidu-infected rabbits.", "contents": "Suppression of lymphocyte response to concanavalin A by mucopolysaccharide material from Treponema pallidum-infected rabbits. The testicular fluid and serum from rabbits infected intratesticularly with Treponema pallidum inhibited the mitogenic response of normal rabbit peripheral blood lymphocytes to concanavalin A. Mucopolysaccharide material present in the testicular fluid and serum was associated with the lymphocyte-inhibitory activity. Degradation of the mucopolysaccharide material with hyaluronidase resulted in the loss of the inhibitory activity of testicular fluid and serum of T. pallidu-infected rabbits."} {"id": "PMID:159265", "title": "Augmentation of lymphocyte surface immunogenicity following treatment with dimethyl-sulphoxide.", "content": "A mixed leucocyte culture is an in vitro tool for assessing differences in cell surface antigenicity between two cell populations. The MLC technique has been used to assess alterations in immunogenicity of rat lymphocytes, when exposed to the agent dimethyl-sulphoxide. Using four different rat strains, DMSO has been shown to be a surface-active agent that significantly increases the immunogenicity of both splenic and peripheral blood rat lymphocytes, as assessed by an increase in MLC reactivity. No augmentation of MLC reactivity is seen when syngeneic lymphocytes are used in the culture system as both effector and stimulator lymphocytes, thus confirming the immunological nature of the enhancement seen in allogeneic cultures.", "contents": "Augmentation of lymphocyte surface immunogenicity following treatment with dimethyl-sulphoxide. A mixed leucocyte culture is an in vitro tool for assessing differences in cell surface antigenicity between two cell populations. The MLC technique has been used to assess alterations in immunogenicity of rat lymphocytes, when exposed to the agent dimethyl-sulphoxide. Using four different rat strains, DMSO has been shown to be a surface-active agent that significantly increases the immunogenicity of both splenic and peripheral blood rat lymphocytes, as assessed by an increase in MLC reactivity. No augmentation of MLC reactivity is seen when syngeneic lymphocytes are used in the culture system as both effector and stimulator lymphocytes, thus confirming the immunological nature of the enhancement seen in allogeneic cultures."} {"id": "PMID:159268", "title": "Alkali-labile sites and post-irradiation effects in gamma-irradiated biologically active double-stranded DNA in aqueous solution.", "content": "Gamma-irradiation of double-stranded RF-DNA of bacteriophage phi X174 in aqueous solution in the presence of oxygen produces at least one type of alkali-labile site. It is lethal and gives rise to breaks by alkali and is identical with the damage which becomes manifest by post-irradiation heat treatment. The effect of alkali is dependent on temperature. Furthermore, the excision repair system is not involved in eliminating lethal nucleotide damage in RFI-DNA.", "contents": "Alkali-labile sites and post-irradiation effects in gamma-irradiated biologically active double-stranded DNA in aqueous solution. Gamma-irradiation of double-stranded RF-DNA of bacteriophage phi X174 in aqueous solution in the presence of oxygen produces at least one type of alkali-labile site. It is lethal and gives rise to breaks by alkali and is identical with the damage which becomes manifest by post-irradiation heat treatment. The effect of alkali is dependent on temperature. Furthermore, the excision repair system is not involved in eliminating lethal nucleotide damage in RFI-DNA."} {"id": "PMID:159271", "title": "Skin and bone lesions (dermato-osteolathyrism), possible side effects of D-penicillamine treatment, in a boy with cystinuria.", "content": "A 2 1/4 year-old boy was treated for cystinuria and urolithiasis with high fluid intake, sodium bicarbonate, and D-penicillamine, over a period of 5 3/4 years, unauthorized interruptions and prescribed pauses included. Therapy was partially sucessful but regrowth of calculi coincided with interruptions of D-penicillamine administration and also with the institution of a low-dose D-penicillamine regime. Flat feet, scoliosis, pectus carinatum, hypermobility of joints, molluscoid pseudotumors and atrophic scars were alarming side effects of D-penicillamine. However, the possibility was not excluded that a forme fruste of an Ehlers-Danlos syndrome preexisted in this boy and was effected by D-penicillamine. Only the molluscoid pseudotumors regressed when D-penicillamine was reduced or omitted temporarily. Osteolathyrism caused by D-penicillamine has hitherto not been reported in man.", "contents": "Skin and bone lesions (dermato-osteolathyrism), possible side effects of D-penicillamine treatment, in a boy with cystinuria. A 2 1/4 year-old boy was treated for cystinuria and urolithiasis with high fluid intake, sodium bicarbonate, and D-penicillamine, over a period of 5 3/4 years, unauthorized interruptions and prescribed pauses included. Therapy was partially sucessful but regrowth of calculi coincided with interruptions of D-penicillamine administration and also with the institution of a low-dose D-penicillamine regime. Flat feet, scoliosis, pectus carinatum, hypermobility of joints, molluscoid pseudotumors and atrophic scars were alarming side effects of D-penicillamine. However, the possibility was not excluded that a forme fruste of an Ehlers-Danlos syndrome preexisted in this boy and was effected by D-penicillamine. Only the molluscoid pseudotumors regressed when D-penicillamine was reduced or omitted temporarily. Osteolathyrism caused by D-penicillamine has hitherto not been reported in man."} {"id": "PMID:159272", "title": "Low temperature activation of post mortem glycogenolysis in bovine skeletal muscle fibres.", "content": "Trimmed strips of sternomandibularis muscles taken from freshly-slaughtered cattle were placed in an isotonic myograph and cooled to 1 degree C. Spontaneous activity due to neuromuscular irritability was minimized by keeping muscle surfaces moist and anaerobic and was monitored by electromyography. Muscle strips were removed and frozen for histochemical analysis after they had completed their initial phase of cold-induced shortening (several hours). Control strips maintained for an equal time at 24 degrees C rarely depleted the stainable glycogen in any of their muscle fibres so as to become PAS-negative. In chilled muscle strips, however, glycogenolysis was activated in some muscle fibres and they became PAS-negative. In serial sections, most of the PAS-negative fibres exhibited strong ATPase and weak succinate dehydrogenase activity. Fibres with weak ATPase and strong succinate dehydrogenase activity rarely became PAS-negative. These results are in agreement with biochemical reports of a cold-induced (less than 5 degrees C) activation of glycolysis in skeletal muscle post mortem. Investigations on untrimmed lengths of excised sternomandibularis muscle indicated that longitudinal muscle damage caused in cutting muscle strips for the myograph and/or their more rapid rate of initial cooling had facilitated the depletion of stainable glycogen.", "contents": "Low temperature activation of post mortem glycogenolysis in bovine skeletal muscle fibres. Trimmed strips of sternomandibularis muscles taken from freshly-slaughtered cattle were placed in an isotonic myograph and cooled to 1 degree C. Spontaneous activity due to neuromuscular irritability was minimized by keeping muscle surfaces moist and anaerobic and was monitored by electromyography. Muscle strips were removed and frozen for histochemical analysis after they had completed their initial phase of cold-induced shortening (several hours). Control strips maintained for an equal time at 24 degrees C rarely depleted the stainable glycogen in any of their muscle fibres so as to become PAS-negative. In chilled muscle strips, however, glycogenolysis was activated in some muscle fibres and they became PAS-negative. In serial sections, most of the PAS-negative fibres exhibited strong ATPase and weak succinate dehydrogenase activity. Fibres with weak ATPase and strong succinate dehydrogenase activity rarely became PAS-negative. These results are in agreement with biochemical reports of a cold-induced (less than 5 degrees C) activation of glycolysis in skeletal muscle post mortem. Investigations on untrimmed lengths of excised sternomandibularis muscle indicated that longitudinal muscle damage caused in cutting muscle strips for the myograph and/or their more rapid rate of initial cooling had facilitated the depletion of stainable glycogen."} {"id": "PMID:159273", "title": "Ultrastructural localization of adenosine triphosphatase in the stellate reticulum, stratum intermedium and ameloblasts of the mouse molar.", "content": "ATPase activity in the developing first mandibular molar of the mouse was demonstrated at the electron microscopic level with the method of Wachstein & Meisel (1957). It was localized along the cell surfaces of the ameloblast and stratum intermedium interface, the stratum intermedium and the stellate reticulum. The ATPase final reaction product was also present at the cell membranes of the proximal region of adjacent ameloblasts and extended to the level of the nuclei. The demonstration of ATPase mainly on the plasma membranes was similar to the observations by other investigators of various non-odontogenic cell types involved in the exchange of materials across plasma membranes.", "contents": "Ultrastructural localization of adenosine triphosphatase in the stellate reticulum, stratum intermedium and ameloblasts of the mouse molar. ATPase activity in the developing first mandibular molar of the mouse was demonstrated at the electron microscopic level with the method of Wachstein & Meisel (1957). It was localized along the cell surfaces of the ameloblast and stratum intermedium interface, the stratum intermedium and the stellate reticulum. The ATPase final reaction product was also present at the cell membranes of the proximal region of adjacent ameloblasts and extended to the level of the nuclei. The demonstration of ATPase mainly on the plasma membranes was similar to the observations by other investigators of various non-odontogenic cell types involved in the exchange of materials across plasma membranes."} {"id": "PMID:159274", "title": "A histoenzymatic study of rat intrafusal muscle fibres.", "content": "The histochemical activities of myofibrillar adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH) and alpha glycerophosphate dehydrogenase (alpha-GPD) were studied in intrafusal muscle fibres of rat fast and slow muscles. The ATPase reaction was carried out after the three standard acid preincubations. The cold K2-EDTA preincubated ATPase reaction product was similar to that seen following the regular or alkali-preincubated ATPase reaction, except that the intermediate bag fibres exhibited much higher activity after cold K2-EDTA preincubation. Following either acetic acid solution or cold and room temperature K2-EDTA-preincubation, followed by the ATPase reaction, chain fibres of the fast muscles vastus lateralis and extensor digitorum longus exhibited a very low amount of reaction product as compared with those of the slow soleus. Veronal acetate and K2-EDTA preincubations (and equally preincubation in acetic acid solution) resulted in acid stable ATPase activity along the entire length of the typical bag fibres but only in the polar regions of the intermediate bag fibres. On the basis of differing alpha-GPD reaction, two sub populations of nuclear chain fibres were discovered in one spindle. It is a matter of conjecture, to what extent the histochemical differences of intrafusal fibres from fast and slow muscles reflects functional distinctions in the response to stretch of muscle spindles from fast and slow muscles.", "contents": "A histoenzymatic study of rat intrafusal muscle fibres. The histochemical activities of myofibrillar adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH) and alpha glycerophosphate dehydrogenase (alpha-GPD) were studied in intrafusal muscle fibres of rat fast and slow muscles. The ATPase reaction was carried out after the three standard acid preincubations. The cold K2-EDTA preincubated ATPase reaction product was similar to that seen following the regular or alkali-preincubated ATPase reaction, except that the intermediate bag fibres exhibited much higher activity after cold K2-EDTA preincubation. Following either acetic acid solution or cold and room temperature K2-EDTA-preincubation, followed by the ATPase reaction, chain fibres of the fast muscles vastus lateralis and extensor digitorum longus exhibited a very low amount of reaction product as compared with those of the slow soleus. Veronal acetate and K2-EDTA preincubations (and equally preincubation in acetic acid solution) resulted in acid stable ATPase activity along the entire length of the typical bag fibres but only in the polar regions of the intermediate bag fibres. On the basis of differing alpha-GPD reaction, two sub populations of nuclear chain fibres were discovered in one spindle. It is a matter of conjecture, to what extent the histochemical differences of intrafusal fibres from fast and slow muscles reflects functional distinctions in the response to stretch of muscle spindles from fast and slow muscles."} {"id": "PMID:159275", "title": "Heparan sulfate at the surface of HeLa cells.", "content": "HeLa cells, labeled with Na235SO4, release into the culture medium 35SO4 bound to plasma membrane vesicles next to 35SO4-glycoproteins and free 35SO4. Plasma membrane vesicles, experimentally produced by treatment with formaldehyde, contain 35SO4 and their surface can be stained with high iron diamine. Scanning of chromatograms of the trypsinate from labeled cells demonstrates radioactivity on the spot of heparan sulfate. It is concluded that HeLa cells synthesize heparan sulfate, which is incorporated at the plasma membrane and released by shedding of small vesicles.", "contents": "Heparan sulfate at the surface of HeLa cells. HeLa cells, labeled with Na235SO4, release into the culture medium 35SO4 bound to plasma membrane vesicles next to 35SO4-glycoproteins and free 35SO4. Plasma membrane vesicles, experimentally produced by treatment with formaldehyde, contain 35SO4 and their surface can be stained with high iron diamine. Scanning of chromatograms of the trypsinate from labeled cells demonstrates radioactivity on the spot of heparan sulfate. It is concluded that HeLa cells synthesize heparan sulfate, which is incorporated at the plasma membrane and released by shedding of small vesicles."} {"id": "PMID:159284", "title": "Structural and functional analysis of cloned deoxyribonucleic acid containing the trpR-thr region of the Escherichia coli chromosome.", "content": "Specialized transducing phages containing the thr-trpR region of the Escherichia coli chromosome were derived from a strain with lambda prophage inserted in thr. Cloning of segments of the chromosomal deoxyribonucleic acid of one such lambda thr + trpR+ phage in various plasmid vectors established that a 1.3-kilobase BamHI fragment carried trpR+ intact. Strains with a multicopy plasmid vector containing the BamHI insert produced 20-fold-higher levels of trp aporepressor than did the wild-type strain of Escherichia coli. Similarly, induction of lambda thr + trpR+ lysogens resulted in increased aporepressor levels. The 1.3-kilobase trpR+ BamHI fragment was inserted in either orientation downstream from lambda pLN in a plasmid vector in which transcription from lambda pL was under the control of a temperature-sensitive lambda repressor. Induction established the orientation of transcription of trpR and led to the production of 100-fold-increased levels of trp aporepressor. A presumptive 23,500-dalton trpR+ polypeptide was detected by using lambda pLNtrpR+ plasmid deoxyribonucleic acid in a cell-free transcription-translation system.", "contents": "Structural and functional analysis of cloned deoxyribonucleic acid containing the trpR-thr region of the Escherichia coli chromosome. Specialized transducing phages containing the thr-trpR region of the Escherichia coli chromosome were derived from a strain with lambda prophage inserted in thr. Cloning of segments of the chromosomal deoxyribonucleic acid of one such lambda thr + trpR+ phage in various plasmid vectors established that a 1.3-kilobase BamHI fragment carried trpR+ intact. Strains with a multicopy plasmid vector containing the BamHI insert produced 20-fold-higher levels of trp aporepressor than did the wild-type strain of Escherichia coli. Similarly, induction of lambda thr + trpR+ lysogens resulted in increased aporepressor levels. The 1.3-kilobase trpR+ BamHI fragment was inserted in either orientation downstream from lambda pLN in a plasmid vector in which transcription from lambda pL was under the control of a temperature-sensitive lambda repressor. Induction established the orientation of transcription of trpR and led to the production of 100-fold-increased levels of trp aporepressor. A presumptive 23,500-dalton trpR+ polypeptide was detected by using lambda pLNtrpR+ plasmid deoxyribonucleic acid in a cell-free transcription-translation system."} {"id": "PMID:159285", "title": "Protein-associated lipid of Bacillus stearothermophilus.", "content": "The composition and patterns of metabolism of phospholipids isolated as part of a lipid-depleted membrane fragment (LDM fragment) and associated with the membrane adenosine triphosphatase complex have been compared with those of the bulk membrane phospholipid. The bulk lipid was extracted from washed membranes with sodium cholate. The LDM fragments, which contained a portion of the electron transport system and the membrane adenosine triphosphatase complex, were purified by chromatography with Sepharose 6B. The LDM fragment preparations contained 0.10 +/- 0.02 mumol of lipid phosphorus per mg of protein, compared with 0.54 +/- 0.05 mumol of lipid phosphorus per mg of protein for washed membranes. The phospholipid associated with the LDM fragments consisted of 78 +/- 4% cardiolipin, 7 +/- 1% phosphatidylglycerol, and 15 +/- 3% phosphatidylethanolamine. Changes in the total membrane lipid composition (produced by culture conditions) did not alter the phospholipid composition of the LDM fragments. The adenosine triphosphate complex was separated from the other components of the LDM fragments by suspension of the fragments in 1% Triton X-100 and precipitation with antibody specific for the F(1) component of the adenosine triphosphatase complex. The phospholipid isolated with the adenosine triphosphatase complex consisted of 86% cardiolipin, 8% phosphatidylglycerol, and 6% phosphatidylethanolamine. In pulse-chase experiments with (32)P and [2-(3)H]glycerol, the labeling patterns of the phosphatididylglycerol and phosphatidylethanolamine associated with the LDM fragments were different from those of the bulk membrane phosphatidylglycerol and phosphatidylethanolamine. It was concluded that at least a portion of the phospholipid isolated with the LDM fragments was part of a native lipid-protein complex.", "contents": "Protein-associated lipid of Bacillus stearothermophilus. The composition and patterns of metabolism of phospholipids isolated as part of a lipid-depleted membrane fragment (LDM fragment) and associated with the membrane adenosine triphosphatase complex have been compared with those of the bulk membrane phospholipid. The bulk lipid was extracted from washed membranes with sodium cholate. The LDM fragments, which contained a portion of the electron transport system and the membrane adenosine triphosphatase complex, were purified by chromatography with Sepharose 6B. The LDM fragment preparations contained 0.10 +/- 0.02 mumol of lipid phosphorus per mg of protein, compared with 0.54 +/- 0.05 mumol of lipid phosphorus per mg of protein for washed membranes. The phospholipid associated with the LDM fragments consisted of 78 +/- 4% cardiolipin, 7 +/- 1% phosphatidylglycerol, and 15 +/- 3% phosphatidylethanolamine. Changes in the total membrane lipid composition (produced by culture conditions) did not alter the phospholipid composition of the LDM fragments. The adenosine triphosphate complex was separated from the other components of the LDM fragments by suspension of the fragments in 1% Triton X-100 and precipitation with antibody specific for the F(1) component of the adenosine triphosphatase complex. The phospholipid isolated with the adenosine triphosphatase complex consisted of 86% cardiolipin, 8% phosphatidylglycerol, and 6% phosphatidylethanolamine. In pulse-chase experiments with (32)P and [2-(3)H]glycerol, the labeling patterns of the phosphatididylglycerol and phosphatidylethanolamine associated with the LDM fragments were different from those of the bulk membrane phosphatidylglycerol and phosphatidylethanolamine. It was concluded that at least a portion of the phospholipid isolated with the LDM fragments was part of a native lipid-protein complex."} {"id": "PMID:159286", "title": "Cyanobacterial ribonucleic acid polymerases recognize lambda promoters.", "content": "We compared the initiation specificities in vitro of deoxyribonucleic acid-dependent ribonucleic acid polymerases purified from two cyanobacteria, Fremyella diplosiphon and Anacystis nidulans, and from Escherichia coli. A restriction fragment made from lambda deoxyribonucleic acid was used as a template. The cyanobacterial and E. coli ribonucleic acid polymerases recognized the same lambda promoters but exhibited different sensitivities to the inhibitor heparin, suggsesting differences in the structure of the initiation complexes.", "contents": "Cyanobacterial ribonucleic acid polymerases recognize lambda promoters. We compared the initiation specificities in vitro of deoxyribonucleic acid-dependent ribonucleic acid polymerases purified from two cyanobacteria, Fremyella diplosiphon and Anacystis nidulans, and from Escherichia coli. A restriction fragment made from lambda deoxyribonucleic acid was used as a template. The cyanobacterial and E. coli ribonucleic acid polymerases recognized the same lambda promoters but exhibited different sensitivities to the inhibitor heparin, suggsesting differences in the structure of the initiation complexes."} {"id": "PMID:159287", "title": "Physical characterization of ilv-lac fusions.", "content": "Electron microscopic heteroduplex analysis and comparative restriction digests have been used to characterize lambda p123(209), the complementary pair of phages used in the Casadaban technique of gene fusion. Derivatives of lambda 1(209) constructed to carry fusions of the lac genes to the control regions of the ilvC and ilvEDA operons were also analyzed. These physical maps have provided confirmation of the genetic models for these constructions and physical specifications important in interpreting the behavior of these ilv-lac fusions.", "contents": "Physical characterization of ilv-lac fusions. Electron microscopic heteroduplex analysis and comparative restriction digests have been used to characterize lambda p123(209), the complementary pair of phages used in the Casadaban technique of gene fusion. Derivatives of lambda 1(209) constructed to carry fusions of the lac genes to the control regions of the ilvC and ilvEDA operons were also analyzed. These physical maps have provided confirmation of the genetic models for these constructions and physical specifications important in interpreting the behavior of these ilv-lac fusions."} {"id": "PMID:159288", "title": "Location of a ColE1 deoxyribonucleic acid region that affects the plaque-forming ability of lambda-ColE1 hybrid bacteriophage.", "content": "The plaque-forming ability of a hybrid phage between plasmidColE1 and phage lambda carrying amber mutations in genes O and P was inhibited by the presence of ColE1 in suppressor-deficient Escherichia coli cells. ColE1 deoxyribonucleic acid regions concerned with this inhibition were examined by using various deletion and transposon insertion derivatives of ColE1, and it was found that the presence of the deoxyribonucleic acid region extending between 420 and 613 base pairs upstream from the initiation site of ColE1 deoxyribonucleic acid replication (J. Tomizawa, H. Ohmori, and R. E. Bird, Proc. Natl. Acad. Sci. U. S. A. 74: 1865--1869, 1977) was essential for this function.", "contents": "Location of a ColE1 deoxyribonucleic acid region that affects the plaque-forming ability of lambda-ColE1 hybrid bacteriophage. The plaque-forming ability of a hybrid phage between plasmidColE1 and phage lambda carrying amber mutations in genes O and P was inhibited by the presence of ColE1 in suppressor-deficient Escherichia coli cells. ColE1 deoxyribonucleic acid regions concerned with this inhibition were examined by using various deletion and transposon insertion derivatives of ColE1, and it was found that the presence of the deoxyribonucleic acid region extending between 420 and 613 base pairs upstream from the initiation site of ColE1 deoxyribonucleic acid replication (J. Tomizawa, H. Ohmori, and R. E. Bird, Proc. Natl. Acad. Sci. U. S. A. 74: 1865--1869, 1977) was essential for this function."} {"id": "PMID:159289", "title": "Suppression of tif-mediated induction of SOS functions in Escherichia coli by an altered dnaB protein.", "content": "The tif-1 mutation in the Escherichia coli recA gene is known to cause induction of the various \"SOS\" functions at high temperature, including massive synthesis of the recA protein, lethal filamentation, elevated mutagenesis, and, in lambda lysogens, induction of prophage. It is shown here that the deoxyribonucleic acid initiation mutation dnaB252 suppresses all these manifestations of tif expression. Induction of lambda by ultraviolet irradiation, however, is not affected by the dnaB252 mutation. No similar suppression of tif is observed with other dnaB mutations affecting deoxyribonucleic acid elongation or with other deoxyribonucleic acid initiation mutations at the dnaA and dnaC loci. The fact that an alteration of the dnaB protein specifically suppresses tif-mediated SOS induction implies a role of the replication apparatus in this process, as has been suggested for ultraviolet induction. The induction of lambda is known to proceed via repressor cleavage, presumably promoted by an activated (protease) form of the recA protein. Since lambda induction is normal after ultraviolet irradiation of the tif-1 dnaB252(lambda) strain, tif-mediated induction in this strain may be blocked in a tif-specific step leading to activation of the recA (tif) protein. It is possible that the recA (tif) mutant protein may be directly involved in the replication complex in processes leading to this activation.", "contents": "Suppression of tif-mediated induction of SOS functions in Escherichia coli by an altered dnaB protein. The tif-1 mutation in the Escherichia coli recA gene is known to cause induction of the various \"SOS\" functions at high temperature, including massive synthesis of the recA protein, lethal filamentation, elevated mutagenesis, and, in lambda lysogens, induction of prophage. It is shown here that the deoxyribonucleic acid initiation mutation dnaB252 suppresses all these manifestations of tif expression. Induction of lambda by ultraviolet irradiation, however, is not affected by the dnaB252 mutation. No similar suppression of tif is observed with other dnaB mutations affecting deoxyribonucleic acid elongation or with other deoxyribonucleic acid initiation mutations at the dnaA and dnaC loci. The fact that an alteration of the dnaB protein specifically suppresses tif-mediated SOS induction implies a role of the replication apparatus in this process, as has been suggested for ultraviolet induction. The induction of lambda is known to proceed via repressor cleavage, presumably promoted by an activated (protease) form of the recA protein. Since lambda induction is normal after ultraviolet irradiation of the tif-1 dnaB252(lambda) strain, tif-mediated induction in this strain may be blocked in a tif-specific step leading to activation of the recA (tif) protein. It is possible that the recA (tif) mutant protein may be directly involved in the replication complex in processes leading to this activation."} {"id": "PMID:159290", "title": "Lambda transducing bacteriophage carrying deletions of the argCBH-rpoBC region of the Escherichia coli chromosome.", "content": "Deletions in the rpoBC region have been transferred to phage lambda and characterized in detail by genetic, structural, and functional tests. We thus extend and confirm knowledge of the organization of this part of the chromosome. The new phages are useful tools for studying the genes for the bacterial transcription and translation machinery.", "contents": "Lambda transducing bacteriophage carrying deletions of the argCBH-rpoBC region of the Escherichia coli chromosome. Deletions in the rpoBC region have been transferred to phage lambda and characterized in detail by genetic, structural, and functional tests. We thus extend and confirm knowledge of the organization of this part of the chromosome. The new phages are useful tools for studying the genes for the bacterial transcription and translation machinery."} {"id": "PMID:159291", "title": "Deoxyribonucleic acid sequence homologies among bacterial insertion sequence elements and genomes of various organisms.", "content": "Plasmid and phage deoxyribonucleic acid (DNA) harboring bacterial insertion sequence (IS) elements IS1, IS2, and IS5 were characterized and used as probes to detect homologous sequences in various procaryotic and eucaryotic genomes. The hybridization method used permits the detection of sequences partially homologous to the elements. Hybridization of the IS-containing probes to each other revealed a region of limited homology between IS1 and IS2. Homologous sequences were then detected by computer analysis of the published IS1 and IS2 nucleotide sequences. The homologous sequence contains a tandemly repeated tetranucleotide sequence which resembles the repeated sequence at the hot spot for spontaneous mutations in the lacI gene (P. J. Farabaugh, U. Schmeissner, M. Hofer, and J. Miller, J. Mol. Biol. 126:847-863, 1978). Homology between the IS elements and various genomes was determined by hybridizing labeled DNA containing IS1, IS2, and IS5 sequences to Southern blots of chromosomal DNA cleaved with restriction endonucleases. IS1 and IS5 appear limited to the enteric bacteria, whereas IS2 sequences can also be detected in Pseudomonas putida, Pseudomonas aeruginosa, and Serratia marcescens. Bacteria which appear not to possess extrachromosomal elements, e.g., Caulobacter crescentus, did not show homology with any insertion sequences tested. In addition, sequences homologous to IS1, IS2, or IS5 were not detected in Saccharomyces cerevisiae, Dictyostelium discoideum, or calf thymus DNA.", "contents": "Deoxyribonucleic acid sequence homologies among bacterial insertion sequence elements and genomes of various organisms. Plasmid and phage deoxyribonucleic acid (DNA) harboring bacterial insertion sequence (IS) elements IS1, IS2, and IS5 were characterized and used as probes to detect homologous sequences in various procaryotic and eucaryotic genomes. The hybridization method used permits the detection of sequences partially homologous to the elements. Hybridization of the IS-containing probes to each other revealed a region of limited homology between IS1 and IS2. Homologous sequences were then detected by computer analysis of the published IS1 and IS2 nucleotide sequences. The homologous sequence contains a tandemly repeated tetranucleotide sequence which resembles the repeated sequence at the hot spot for spontaneous mutations in the lacI gene (P. J. Farabaugh, U. Schmeissner, M. Hofer, and J. Miller, J. Mol. Biol. 126:847-863, 1978). Homology between the IS elements and various genomes was determined by hybridizing labeled DNA containing IS1, IS2, and IS5 sequences to Southern blots of chromosomal DNA cleaved with restriction endonucleases. IS1 and IS5 appear limited to the enteric bacteria, whereas IS2 sequences can also be detected in Pseudomonas putida, Pseudomonas aeruginosa, and Serratia marcescens. Bacteria which appear not to possess extrachromosomal elements, e.g., Caulobacter crescentus, did not show homology with any insertion sequences tested. In addition, sequences homologous to IS1, IS2, or IS5 were not detected in Saccharomyces cerevisiae, Dictyostelium discoideum, or calf thymus DNA."} {"id": "PMID:159292", "title": "The effects of linoleate hydroperoxide on respiration and oxidative phosphorylation of rat liver mitochondria.", "content": "Linoleate hydropepoxide, purified by silica gel chromatography and at concentrations 70-100 nmol/mg mitochondrial protein, activated state 4 respiration and Mg-ATPase activity of mitochondria to levels of 80% and 25%, respectively, of those induced by 300 microM DNP, and completely inhibited oxidative phosphorylation. These effects are the same as those caused by linoleate, but the hydroperoxide caused more rapid degeneration of the activated respiration of mitochondria than linoleate. Further addition of the hydroperoxide induced oligomycin-insensitive Mg-ATPase to a level 3 times that obtained with DNP, accompanied by clearing of the mitochondrial suspension and release of malate dehydrogenase from the matrix. The extent of the effects caused by the methyl ester of linoleate hydroperoxide was much less than by the free acid.", "contents": "The effects of linoleate hydroperoxide on respiration and oxidative phosphorylation of rat liver mitochondria. Linoleate hydropepoxide, purified by silica gel chromatography and at concentrations 70-100 nmol/mg mitochondrial protein, activated state 4 respiration and Mg-ATPase activity of mitochondria to levels of 80% and 25%, respectively, of those induced by 300 microM DNP, and completely inhibited oxidative phosphorylation. These effects are the same as those caused by linoleate, but the hydroperoxide caused more rapid degeneration of the activated respiration of mitochondria than linoleate. Further addition of the hydroperoxide induced oligomycin-insensitive Mg-ATPase to a level 3 times that obtained with DNP, accompanied by clearing of the mitochondrial suspension and release of malate dehydrogenase from the matrix. The extent of the effects caused by the methyl ester of linoleate hydroperoxide was much less than by the free acid."} {"id": "PMID:159293", "title": "Isolation and characterization of mucopolysaccharides from rat liver mitochondria.", "content": "Mucopolysaccharides were isolated from rat liver mitochondria which had been labeled with 35S-sulfate. They were prepared from trichloroacetic acid (TCA)-insoluble and -soluble fractions of lipid-free mitochondria. These fractions were digested with pronase exhaustively, and the mucopolysaccharides were recovered in the void volume fractions of gel filtration of the pronase digests on Sephadex G-50, monitored by radioactivity determination. Identification of these mucopolysaccharides was based on electrophoresis on cellulose acetate film using three different media, enzymatic and chemical degradations specific to each type of mucopolysaccharide, using chondroitinases, heparitinase, and nitrous acid. From the TCA-insoluble fraction, chondroitin sulfate A and dermatan sulfate were obtained in a ratio of about 1 : 2, based on 35S-radioactivities, whereas the TCA-soluble fraction yielded chondroitin sulfates A/C, dermatan sulfate, and heparan sulfate in a ratio of about 1 : 3 : 12. The total amount of mitochondrial mucopolysaccharides was about 3 mg/g protein, distributed between the TCA-insoluble and -soluble fractions in a ratio of about 1 : 3.", "contents": "Isolation and characterization of mucopolysaccharides from rat liver mitochondria. Mucopolysaccharides were isolated from rat liver mitochondria which had been labeled with 35S-sulfate. They were prepared from trichloroacetic acid (TCA)-insoluble and -soluble fractions of lipid-free mitochondria. These fractions were digested with pronase exhaustively, and the mucopolysaccharides were recovered in the void volume fractions of gel filtration of the pronase digests on Sephadex G-50, monitored by radioactivity determination. Identification of these mucopolysaccharides was based on electrophoresis on cellulose acetate film using three different media, enzymatic and chemical degradations specific to each type of mucopolysaccharide, using chondroitinases, heparitinase, and nitrous acid. From the TCA-insoluble fraction, chondroitin sulfate A and dermatan sulfate were obtained in a ratio of about 1 : 2, based on 35S-radioactivities, whereas the TCA-soluble fraction yielded chondroitin sulfates A/C, dermatan sulfate, and heparan sulfate in a ratio of about 1 : 3 : 12. The total amount of mitochondrial mucopolysaccharides was about 3 mg/g protein, distributed between the TCA-insoluble and -soluble fractions in a ratio of about 1 : 3."} {"id": "PMID:159294", "title": "Demonstration and quantitation of catalytic and noncatalytic bound ATP in submitochondrial particles during oxidative phosphorylation.", "content": "Techniques are described for studying the labeling of ADP and ATP bound to the ATP synthase complex of beef heart submitochondrial particles catalyzing oxidative phosphorylation. These suffice for measurements of bound nucleotides during the time required for a single turnover, during steady state net ATP synthesis, or under quasiequilibrium conditions of ATP formation and hydrolysis. Results show that the \"tightly bound\" ATP associated with isolated submitochondrial particles does not become labeled by medium [32P]Pi rapidly enough to qualify as an intermediate in ATP synthesis. In contrast to chloroplast preparations, little or no bound [32P]Pi committed to ATP formation is present on particles during steady state synthesis. Also, highly active particles synthesizing ATP from [32P]Pi and filtered after EDTA addition have no detectable bound [32P]ATP even though several ATPs have been made per synthase complex. However, under quasiequilibrium conditions membrane-bound ADP and ATP are present whose labeling characteristics qualify them as intermediates in ATP synthesis. In addition, a hexokinase-accessibility approach shows the presence of a steady level of bound ATP. Lack of detection of bound intermediates under other conditions is regarded as reflecting the ready reversibility of oxidative phosphorylation, with consequent facile cleavage of bound ATP and release of bound Pi.", "contents": "Demonstration and quantitation of catalytic and noncatalytic bound ATP in submitochondrial particles during oxidative phosphorylation. Techniques are described for studying the labeling of ADP and ATP bound to the ATP synthase complex of beef heart submitochondrial particles catalyzing oxidative phosphorylation. These suffice for measurements of bound nucleotides during the time required for a single turnover, during steady state net ATP synthesis, or under quasiequilibrium conditions of ATP formation and hydrolysis. Results show that the \"tightly bound\" ATP associated with isolated submitochondrial particles does not become labeled by medium [32P]Pi rapidly enough to qualify as an intermediate in ATP synthesis. In contrast to chloroplast preparations, little or no bound [32P]Pi committed to ATP formation is present on particles during steady state synthesis. Also, highly active particles synthesizing ATP from [32P]Pi and filtered after EDTA addition have no detectable bound [32P]ATP even though several ATPs have been made per synthase complex. However, under quasiequilibrium conditions membrane-bound ADP and ATP are present whose labeling characteristics qualify them as intermediates in ATP synthesis. In addition, a hexokinase-accessibility approach shows the presence of a steady level of bound ATP. Lack of detection of bound intermediates under other conditions is regarded as reflecting the ready reversibility of oxidative phosphorylation, with consequent facile cleavage of bound ATP and release of bound Pi."} {"id": "PMID:159296", "title": "On the subunit stoichiometry of the F1-ATPase and the sites in it that react specifically with p-fluorosulfonylbenzoyl-5'-adenosine.", "content": "During the inactivation of the nucleotide-free F1-ATPase at pH 7.0, by p-fluorosulfonyl[14C]benzoyl-5'-adenosine ([14C]FSBA) in the presence of 20% glycerol, about 4.5 g atoms of 14C are incorporated/350,000 g of enzyme. Isolation of the subunits has shown: (a) over 90% of the incorporated label is associated with the alpha and beta subunits; (b) the amount of label incorporated into the alpha subunit is about 0.5 g atoms/mol which is nonspecifically associated with a number of tyrosine and lysine residues; (c) the amount of radioactivity incorporated into the beta subunit is about 0.9 g atoms/mol which correlates with the degree of inactivation of the enzyme and resides on a single tyrosine residue; (d) up to 2.2 mol of alpha subunit have been isolated from each mole of inactivated enzyme; and (e) about 2 mol of beta subunit have been isolated from each mole of inactivated enzyme. These results account for the incorporation of 4.5 g atoms of 14C which are incorporated/mol of ATPase during inactivation if there are three copies each of the alpha and beta subunit present in the enzyme. It has also been shown that 4-chloro-7-nitrobenzofurazan (NBD-Cl) and FSBA react with different tyrosine residues when they inactivate the ATPase. In addition, it has been shown that the ATPase inactivated with FSBA retains the capacity to bind up to 2.2 mol of [14C]ADP/350,000 g of enzyme.", "contents": "On the subunit stoichiometry of the F1-ATPase and the sites in it that react specifically with p-fluorosulfonylbenzoyl-5'-adenosine. During the inactivation of the nucleotide-free F1-ATPase at pH 7.0, by p-fluorosulfonyl[14C]benzoyl-5'-adenosine ([14C]FSBA) in the presence of 20% glycerol, about 4.5 g atoms of 14C are incorporated/350,000 g of enzyme. Isolation of the subunits has shown: (a) over 90% of the incorporated label is associated with the alpha and beta subunits; (b) the amount of label incorporated into the alpha subunit is about 0.5 g atoms/mol which is nonspecifically associated with a number of tyrosine and lysine residues; (c) the amount of radioactivity incorporated into the beta subunit is about 0.9 g atoms/mol which correlates with the degree of inactivation of the enzyme and resides on a single tyrosine residue; (d) up to 2.2 mol of alpha subunit have been isolated from each mole of inactivated enzyme; and (e) about 2 mol of beta subunit have been isolated from each mole of inactivated enzyme. These results account for the incorporation of 4.5 g atoms of 14C which are incorporated/mol of ATPase during inactivation if there are three copies each of the alpha and beta subunit present in the enzyme. It has also been shown that 4-chloro-7-nitrobenzofurazan (NBD-Cl) and FSBA react with different tyrosine residues when they inactivate the ATPase. In addition, it has been shown that the ATPase inactivated with FSBA retains the capacity to bind up to 2.2 mol of [14C]ADP/350,000 g of enzyme."} {"id": "PMID:159299", "title": "Tightly bound magnesium in mitochondrial adenosine triphosphatase from beef heart.", "content": "Tightly bound magnesium was found in soluble, purified ATPase (F1) from beef heart mitochondria in the amount of 1 mol/mol of F1. Iron, zinc, cobalt, manganese, calcium, sodium, copper, and potassium were not tightly bound at stoichiometric levels. Removal of magnesium by chelating agents caused loss of ATPase activity. Removal of tightly bound nucleotide by gel filtration in 50% glycerol- or 60 mM K2SO4-containing buffers did not remove magnesium. Cold dissociation did release magnesium when complete denaturation was accomplished. The results suggest that magnesium is an integral part of F1, that it is required for activity, and that magnesium and nucleotides are tightly bound at separate sites. The idea that the tightly bound nucleotides are not complexed with cations suggests certain structural requirements at their binding sites which might account for the unusual properties of the sites.", "contents": "Tightly bound magnesium in mitochondrial adenosine triphosphatase from beef heart. Tightly bound magnesium was found in soluble, purified ATPase (F1) from beef heart mitochondria in the amount of 1 mol/mol of F1. Iron, zinc, cobalt, manganese, calcium, sodium, copper, and potassium were not tightly bound at stoichiometric levels. Removal of magnesium by chelating agents caused loss of ATPase activity. Removal of tightly bound nucleotide by gel filtration in 50% glycerol- or 60 mM K2SO4-containing buffers did not remove magnesium. Cold dissociation did release magnesium when complete denaturation was accomplished. The results suggest that magnesium is an integral part of F1, that it is required for activity, and that magnesium and nucleotides are tightly bound at separate sites. The idea that the tightly bound nucleotides are not complexed with cations suggests certain structural requirements at their binding sites which might account for the unusual properties of the sites."} {"id": "PMID:159300", "title": "Phosphocreatine does not inhibit rabbit muscle phosphofructokinase or pyruvate kinase.", "content": "Certain phosphocreatine preparations contain a contaminant that inhibits phosphofructokinase and pyruvate kinase assays. The contaminant can be separated from phosphocreatine by anion exchange chromatography. After appropriate purification, phosphocreatine has no effect on phosphofructokinase or pyruvate kinase; thus, there is no evidence that it serves muscle as a regulator of these enzymes. Although the inhibitory preparations of phosphocreatine contain inorganic phosphate and trace amounts of more negatively charged phosphorylated contaminants, the inhibitor is not inorganic phosphate or pyrophosphate. The nature of the inhibitor remains to be determined.", "contents": "Phosphocreatine does not inhibit rabbit muscle phosphofructokinase or pyruvate kinase. Certain phosphocreatine preparations contain a contaminant that inhibits phosphofructokinase and pyruvate kinase assays. The contaminant can be separated from phosphocreatine by anion exchange chromatography. After appropriate purification, phosphocreatine has no effect on phosphofructokinase or pyruvate kinase; thus, there is no evidence that it serves muscle as a regulator of these enzymes. Although the inhibitory preparations of phosphocreatine contain inorganic phosphate and trace amounts of more negatively charged phosphorylated contaminants, the inhibitor is not inorganic phosphate or pyrophosphate. The nature of the inhibitor remains to be determined."} {"id": "PMID:159302", "title": "Binding of mitochondrial ribosomal proteins to a mitochondrial ribosomal precursor RNA containing a 2.3-kilobase intron.", "content": "In Neurospora, the gene encoding the mitochondrial large subunit (25 S) rRNA contains an intervening sequence of approximately 2.3 kilobases. We have recently identified two temperature-sensitive, nuclear mutants (289-67 and 299-9) which are defective in splicing of the 25 S RNA. When grown at the nonpermissive temperature (37 degrees C), the mutants show decreased ratios of 25 S/19 S RNA and accumulate a novel 35 S RNA which appears to be a continuous transcript of the 25 S RNA gene, including the intervening sequence. In the present work, mitochondrial ribonucleoprotein particles present in the 50 S subunit peak from wild type and mutant 299-9 were analyzed by equilibrium centrifugation in CsCl gradients containing 25 mM MgCl2. The results show that 35 S RNA can be isolated as part of a ribonucleoprotein particle associated with nearly all of the large subunit ribosomal proteins. However, the particles appear to be less stable in CsCl gradients and more sensitive to nucleolytic degradation than particles derived from mature large subunits. Our results indicate that binding of ribosomal proteins to 35 S RNA could precede removal of the intron, but that removal of the intron may be required to achieve stable protein binding.", "contents": "Binding of mitochondrial ribosomal proteins to a mitochondrial ribosomal precursor RNA containing a 2.3-kilobase intron. In Neurospora, the gene encoding the mitochondrial large subunit (25 S) rRNA contains an intervening sequence of approximately 2.3 kilobases. We have recently identified two temperature-sensitive, nuclear mutants (289-67 and 299-9) which are defective in splicing of the 25 S RNA. When grown at the nonpermissive temperature (37 degrees C), the mutants show decreased ratios of 25 S/19 S RNA and accumulate a novel 35 S RNA which appears to be a continuous transcript of the 25 S RNA gene, including the intervening sequence. In the present work, mitochondrial ribonucleoprotein particles present in the 50 S subunit peak from wild type and mutant 299-9 were analyzed by equilibrium centrifugation in CsCl gradients containing 25 mM MgCl2. The results show that 35 S RNA can be isolated as part of a ribonucleoprotein particle associated with nearly all of the large subunit ribosomal proteins. However, the particles appear to be less stable in CsCl gradients and more sensitive to nucleolytic degradation than particles derived from mature large subunits. Our results indicate that binding of ribosomal proteins to 35 S RNA could precede removal of the intron, but that removal of the intron may be required to achieve stable protein binding."} {"id": "PMID:159303", "title": "Phosphorylation and dephosphorylation kinetics of potassium-stimulated ATP phosphohydrolase from hog gastric mucosa.", "content": "Partial reactions of potassium-stimulated ATP phosphohydrolase from hog gastric mucosa were studied by means of a rapid-mixing apparatus. At 21 degrees C, in the presence of 2 mM MgCl2 and 5 microM [gamma-32P]ATP there was a rapid phosphorylation of the enzyme with a pseudofirst order rate constant of 1400 min-1. Addition of the ATP about 120 ms before the MgCl2 increased this rate constant to 4400 min-1. In the absence of MgCl2 there was no phosphorylation. Addition of 4 or 10 mM KCl to the phosphoenzyme which had been formed in the absence of KCl produced a rapid initial rate of dephosphorylation (k = 2600 and 3200 min-1 respectively). An additional slow component of dephosphorylation was observed when unlabeled ATP was added together with the KCl (k = 700 to 900 min-1). At a 4 mM concentration, KCl stimulated the ATPase activity about 9-fold. At higher concentrations, the activity was reduced in parallel with a reduction of the steady state level of phosphoenzyme. Addition of KCl to the enzyme before the addition of ATP plus MgCl2 resulted in a low rate and extent of phosphorylation. KCl appeared to inhibit the phosphorylation at a level preceeding the E.ATP complex.", "contents": "Phosphorylation and dephosphorylation kinetics of potassium-stimulated ATP phosphohydrolase from hog gastric mucosa. Partial reactions of potassium-stimulated ATP phosphohydrolase from hog gastric mucosa were studied by means of a rapid-mixing apparatus. At 21 degrees C, in the presence of 2 mM MgCl2 and 5 microM [gamma-32P]ATP there was a rapid phosphorylation of the enzyme with a pseudofirst order rate constant of 1400 min-1. Addition of the ATP about 120 ms before the MgCl2 increased this rate constant to 4400 min-1. In the absence of MgCl2 there was no phosphorylation. Addition of 4 or 10 mM KCl to the phosphoenzyme which had been formed in the absence of KCl produced a rapid initial rate of dephosphorylation (k = 2600 and 3200 min-1 respectively). An additional slow component of dephosphorylation was observed when unlabeled ATP was added together with the KCl (k = 700 to 900 min-1). At a 4 mM concentration, KCl stimulated the ATPase activity about 9-fold. At higher concentrations, the activity was reduced in parallel with a reduction of the steady state level of phosphoenzyme. Addition of KCl to the enzyme before the addition of ATP plus MgCl2 resulted in a low rate and extent of phosphorylation. KCl appeared to inhibit the phosphorylation at a level preceeding the E.ATP complex."} {"id": "PMID:159304", "title": "The effects of kallikrein, plasmin, and thrombin on hog kidney renin.", "content": "Pretreatment of hog high molecular weight renin for 30 min at 37 degrees C with 0.12 unit of either kallikrein or thrombin significantly increased (p less than 0.001) the amount of angiotensin I formed during subsequent incubations with homologous angiotensinogen. However, the thrombin-treated hog renin had 13 times more activity than the kallikrein-treated enzyme. Aprotinin did not inhibit the kallikrein-mediated activation of renin; the results indicated that aprotinin inhibited renin preferentially. Plasmin (0.25 unit) had little effect on the activity of high molecular weight renin. The molecular weight of hog renin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was not altered after exposure to either kallikrein, thrombin, or plasmin. These results do not exclude the occurrence of a limited proteolytic event or a conformational change beyond the detection of the current method. The data show that the activation of hog high molecular weight renin by thrombin and kallikrein was not associated with the conversion of renin to Mr = 43,000.", "contents": "The effects of kallikrein, plasmin, and thrombin on hog kidney renin. Pretreatment of hog high molecular weight renin for 30 min at 37 degrees C with 0.12 unit of either kallikrein or thrombin significantly increased (p less than 0.001) the amount of angiotensin I formed during subsequent incubations with homologous angiotensinogen. However, the thrombin-treated hog renin had 13 times more activity than the kallikrein-treated enzyme. Aprotinin did not inhibit the kallikrein-mediated activation of renin; the results indicated that aprotinin inhibited renin preferentially. Plasmin (0.25 unit) had little effect on the activity of high molecular weight renin. The molecular weight of hog renin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was not altered after exposure to either kallikrein, thrombin, or plasmin. These results do not exclude the occurrence of a limited proteolytic event or a conformational change beyond the detection of the current method. The data show that the activation of hog high molecular weight renin by thrombin and kallikrein was not associated with the conversion of renin to Mr = 43,000."} {"id": "PMID:159306", "title": "Mutants of Escherichia coli that do not contain 1,4-diaminobutane (putrescine) or spermidine.", "content": "Strains of Escherichia coli K12 have been constructed which do not contain any of the polyamines normally present in a wild type strain, namely, 1,4-diaminobutane (putrescine) and spermidine. This phenotype arises as a consequence of the assembly into these strains of deletion mutations in speA (arginine decarboxylase), speB (agmatine ureohydrolase), speC (ornithine decarboxylase), and speD (adenosylmethionine decarboxylase). The polyamine-deficient strains grow indefinitely in the absence of polyamines but with a growth rate one-third of that found in the presence of polyamines. These strains can act as hosts for bacteriophages T4, T7, and f2, although the latter phage is poorly adsorbed; they can also maintain F' factors, ColE1 and P1 plasmids, and lysogeny by bacteriophage lambda. In contrast, the production of bacteriophage lambda in the absence of polyamines is strikingly decreased (greater than 99%) either after infection of a nonlysogen or after induction of a lysogen. A polyamine-deficient Hfr strain can transfer its chromosome to a recipient at a normal rate, but the number of recombinants observed in a cross is decreased approximately 300-fold. No such effect is observed when only the F- recipient strain in a cross is polyamine deficient.", "contents": "Mutants of Escherichia coli that do not contain 1,4-diaminobutane (putrescine) or spermidine. Strains of Escherichia coli K12 have been constructed which do not contain any of the polyamines normally present in a wild type strain, namely, 1,4-diaminobutane (putrescine) and spermidine. This phenotype arises as a consequence of the assembly into these strains of deletion mutations in speA (arginine decarboxylase), speB (agmatine ureohydrolase), speC (ornithine decarboxylase), and speD (adenosylmethionine decarboxylase). The polyamine-deficient strains grow indefinitely in the absence of polyamines but with a growth rate one-third of that found in the presence of polyamines. These strains can act as hosts for bacteriophages T4, T7, and f2, although the latter phage is poorly adsorbed; they can also maintain F' factors, ColE1 and P1 plasmids, and lysogeny by bacteriophage lambda. In contrast, the production of bacteriophage lambda in the absence of polyamines is strikingly decreased (greater than 99%) either after infection of a nonlysogen or after induction of a lysogen. A polyamine-deficient Hfr strain can transfer its chromosome to a recipient at a normal rate, but the number of recombinants observed in a cross is decreased approximately 300-fold. No such effect is observed when only the F- recipient strain in a cross is polyamine deficient."} {"id": "PMID:159307", "title": "Phenylglyoxal modification of cardiac myosin S-1. Evidence for essential arginine residues at the active site.", "content": "The role of arginine residues in the catalytic activity of cardiac myosin subfragment-1 (S-1) was investigated by selective modification with phenylglyoxal. Incorporation of about 2.8 mol of phenylglyoxal/mol of S-1 decreased Ca2+-ATPase activity about 50%. Gelation of the protein occurred at about 70% inactivation; however, extrapolation to complete inactivation indicated that loss of activity correlated with modification of about 4 arginyls/mol. Partial inactivation of S-1 with phenylglyoxal also decreased MgADP binding markedly. When S-1 was modified in the presence of 5 mM MgADP, only 2 arginyls/mol were blocked and there was almost complete protection against loss of Ca2+-ATPase activity and ability to bind MgADP. Similar protection against inactivation by phenylglyoxal was obtained with MgATP or sodium pyrophosphate, but not with MgAMP or magnesium adenosine. These results suggest that 2 arginyls/myosin head are important for enzymatic activity, possibly serving as attachment points between enzyme and substrate. These essential arginyls were localized to a 17,000-dalton cyanogen bromide peptide from the heavy chain fragment of S-1.", "contents": "Phenylglyoxal modification of cardiac myosin S-1. Evidence for essential arginine residues at the active site. The role of arginine residues in the catalytic activity of cardiac myosin subfragment-1 (S-1) was investigated by selective modification with phenylglyoxal. Incorporation of about 2.8 mol of phenylglyoxal/mol of S-1 decreased Ca2+-ATPase activity about 50%. Gelation of the protein occurred at about 70% inactivation; however, extrapolation to complete inactivation indicated that loss of activity correlated with modification of about 4 arginyls/mol. Partial inactivation of S-1 with phenylglyoxal also decreased MgADP binding markedly. When S-1 was modified in the presence of 5 mM MgADP, only 2 arginyls/mol were blocked and there was almost complete protection against loss of Ca2+-ATPase activity and ability to bind MgADP. Similar protection against inactivation by phenylglyoxal was obtained with MgATP or sodium pyrophosphate, but not with MgAMP or magnesium adenosine. These results suggest that 2 arginyls/myosin head are important for enzymatic activity, possibly serving as attachment points between enzyme and substrate. These essential arginyls were localized to a 17,000-dalton cyanogen bromide peptide from the heavy chain fragment of S-1."} {"id": "PMID:159308", "title": "Mapping and cloning of Neurospora crassa mitochondrial transfer RNA genes.", "content": "We have obtained collections of recombinant Escherichia coli plasmids containing restriction fragments of Neurospora crassa mitochondrial DNA cloned into pBR322. By hybridization of 32P end-labeled total mitochondrial tRNAs and seven different purified tRNAs to restriction digests of mitochondrial DNA and of recombinant plasmids carrying specific restriction fragments, we have located the tRNA genes on the mitochondrial DNA. We have found that the mitochondrial tRNA genes are present in two major clusters, one between the two ribosomal RNA genes and the second closely following the large rRNA gene. Only one of the two DNA strands within these clusters codes for tRNAs. All of the genes for the seven specific purified tRNAs examined--those for alanine, formylmethionine, leucine 1, leucine 2, threonine, tyrosine, and valine--lie within these clusters. Interestingly, the formylmethionine tRNA hybridizes to two loci within one of these gene clusters. We have obtained a fairly detailed restriction map of part of this cluster and have shown that the two \"putative\" genes for formylmethionine tRNA are not arranged in tandem but are separated by more than 900 base pairs and by at least two other tRNA genes, those for alanine and for leucine 1 tRNAs.", "contents": "Mapping and cloning of Neurospora crassa mitochondrial transfer RNA genes. We have obtained collections of recombinant Escherichia coli plasmids containing restriction fragments of Neurospora crassa mitochondrial DNA cloned into pBR322. By hybridization of 32P end-labeled total mitochondrial tRNAs and seven different purified tRNAs to restriction digests of mitochondrial DNA and of recombinant plasmids carrying specific restriction fragments, we have located the tRNA genes on the mitochondrial DNA. We have found that the mitochondrial tRNA genes are present in two major clusters, one between the two ribosomal RNA genes and the second closely following the large rRNA gene. Only one of the two DNA strands within these clusters codes for tRNAs. All of the genes for the seven specific purified tRNAs examined--those for alanine, formylmethionine, leucine 1, leucine 2, threonine, tyrosine, and valine--lie within these clusters. Interestingly, the formylmethionine tRNA hybridizes to two loci within one of these gene clusters. We have obtained a fairly detailed restriction map of part of this cluster and have shown that the two \"putative\" genes for formylmethionine tRNA are not arranged in tandem but are separated by more than 900 base pairs and by at least two other tRNA genes, those for alanine and for leucine 1 tRNAs."} {"id": "PMID:159309", "title": "Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L 5222.", "content": "The newly synthesized nitrosoureas 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea (Acetamido-CNU), 1-(2-chloroethyl)-1-nitroso-3-(4-morpholino)-urea (Morpholino-CNU), 1-(2-chloroethyl)-1-nitroso-3-(1-piperidino)-urea (Piperidino-CNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-ethylmethanesulfonate (Ethylmethanesulfonato-CNU) were compared in their chemotherapeutic activity against preterminal rat leukemia L 5222 with BCNU, CCNU, MeCCNU, Chlorozotocin, and Hydroxyethyl-CNU. With respect to the dose range effecting a median survival time of more than 90 days, MeCCNU was superior to the other substances. Chlorozotocin, on the other hand, was the only substance which achieved no cures in this experimental arrangement. From the four newly introduced substances the water-soluble substances Acetamido-CNU and Morpholino-CNU were approximately comparable to CCNU with regard to the dose range effecting a median survival time of greater than 90 days. Piperidino-CNU and Ethylmethanesulfonato-CNU also effected cures; however, only Piperidino-CNU in one dosage effected a median survival time of greater than 90 days.", "contents": "Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L 5222. The newly synthesized nitrosoureas 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea (Acetamido-CNU), 1-(2-chloroethyl)-1-nitroso-3-(4-morpholino)-urea (Morpholino-CNU), 1-(2-chloroethyl)-1-nitroso-3-(1-piperidino)-urea (Piperidino-CNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-ethylmethanesulfonate (Ethylmethanesulfonato-CNU) were compared in their chemotherapeutic activity against preterminal rat leukemia L 5222 with BCNU, CCNU, MeCCNU, Chlorozotocin, and Hydroxyethyl-CNU. With respect to the dose range effecting a median survival time of more than 90 days, MeCCNU was superior to the other substances. Chlorozotocin, on the other hand, was the only substance which achieved no cures in this experimental arrangement. From the four newly introduced substances the water-soluble substances Acetamido-CNU and Morpholino-CNU were approximately comparable to CCNU with regard to the dose range effecting a median survival time of greater than 90 days. Piperidino-CNU and Ethylmethanesulfonato-CNU also effected cures; however, only Piperidino-CNU in one dosage effected a median survival time of greater than 90 days."} {"id": "PMID:159310", "title": "Characterization of gastric mucosal membranes. X. Immunological studies of gastric (H+ + K+)-ATPase.", "content": "Gastric mucosal homogenates from hog were fractionated by differential and density gradient centrifugation and free-flow electrophoresis. The two major membrane fractions (FI and FII) thus obtained are distinct both enzymically and in terms of transport reactivity. This heterogenicity extends to their antigenic activity. Purified antibodies which were raised against the K+-ATPase-containing H+ transport fraction FI were of two types: inhibitory and non-inhibitory. Inhibitory antibodies reduced the K+-ATPase activity by approximately 80% and the K+-p-nitro-phenylphosphatase activity by approximately 40% in a concentration-dependent manner, while the small Mg++-dependent component of the enzyme activity was unaffected. Antibodies inhibiting the K+-ATPase also inhibited H+ transport. These antibodies did not cross-react with the other major membrane fraction isolated by free-flow electrophoresis, FII, and gave a single band on rocket immunoelectrophoresis. Antibodies against this FII fraction also did not react with the K+-ATPase and were heterogeneous, giving at least four bands with rocket immunoelectrophoresis and inhibiting both the 5'-nucleotidase and Mg++-ATPase of this fraction. Immunofluorescent staining of tissue sections showed that the FI was derived from the parietal cell of gastric tissue and was localized to the supranuclear area of the cell. Staining of isolated rat gastric cell suspensions by FI antibodies confirmed the selectivity of the antibody and showed a polar, plasma membrane localization. FII antibodies also largely stained the parietal cells in tissue sections. In the 16 hog tissues tested, FI antibodies cross-reacted only with gastric fundus, thyroid and weakly with thymus. Immunoelectronmicroscopy showed that FI antibodies reacted strongly with the secretory membrane at the apical cell surface of the parietal cells and at the secretory canaliculi, weakly with the apical surface of the zymogen cell, and not with the basal-lateral surface of the cells. Thus, the protontranslocating ATPase is localized in the parietal cells and in the region postulated to be the site of acid secretion.", "contents": "Characterization of gastric mucosal membranes. X. Immunological studies of gastric (H+ + K+)-ATPase. Gastric mucosal homogenates from hog were fractionated by differential and density gradient centrifugation and free-flow electrophoresis. The two major membrane fractions (FI and FII) thus obtained are distinct both enzymically and in terms of transport reactivity. This heterogenicity extends to their antigenic activity. Purified antibodies which were raised against the K+-ATPase-containing H+ transport fraction FI were of two types: inhibitory and non-inhibitory. Inhibitory antibodies reduced the K+-ATPase activity by approximately 80% and the K+-p-nitro-phenylphosphatase activity by approximately 40% in a concentration-dependent manner, while the small Mg++-dependent component of the enzyme activity was unaffected. Antibodies inhibiting the K+-ATPase also inhibited H+ transport. These antibodies did not cross-react with the other major membrane fraction isolated by free-flow electrophoresis, FII, and gave a single band on rocket immunoelectrophoresis. Antibodies against this FII fraction also did not react with the K+-ATPase and were heterogeneous, giving at least four bands with rocket immunoelectrophoresis and inhibiting both the 5'-nucleotidase and Mg++-ATPase of this fraction. Immunofluorescent staining of tissue sections showed that the FI was derived from the parietal cell of gastric tissue and was localized to the supranuclear area of the cell. Staining of isolated rat gastric cell suspensions by FI antibodies confirmed the selectivity of the antibody and showed a polar, plasma membrane localization. FII antibodies also largely stained the parietal cells in tissue sections. In the 16 hog tissues tested, FI antibodies cross-reacted only with gastric fundus, thyroid and weakly with thymus. Immunoelectronmicroscopy showed that FI antibodies reacted strongly with the secretory membrane at the apical cell surface of the parietal cells and at the secretory canaliculi, weakly with the apical surface of the zymogen cell, and not with the basal-lateral surface of the cells. Thus, the protontranslocating ATPase is localized in the parietal cells and in the region postulated to be the site of acid secretion."} {"id": "PMID:159311", "title": "Poor mixed lymphocyte reaction stimulatory capacity of leukemic B cells of chronic lymphocytic leukemia patients despite the presence of Ia antigens.", "content": "The human Ia-like antigens, selectively expressed on B lymphocytes, are now recognized to be closely associated with, or identical to, the gene products of the major histocompatibility complex responsible for stimulation in the mixed lymphocyte reaction. The leukemic B lymphocytes of patients with chronic lymphocytic leukemia express these antigens very well. In the present study they were readily detected by several techniques utilizing both allo- and heteroantisera. However, the leukemic B cells from most patients were found to be extremely poor stimulating cells in the mixed lymphocyte reaction. This was particularly apparent when comparisons were made on a B-cell basis with isolated normal B lymphocytes. Leukemic cell death, abnormal kinetics of leukemic cell-mediated stimulation, and serum or cellular suppressor factors do not appear to explain these findings. Studies comparing cells from a leukemic patient with those of her HLA identical sibling and results of mixed lymphocyte reactions between normal and leukemic subjects discordant for D-region-associated Ia antigens ruled out genetic explanations for the differences observed. Experiments with normal peripheral blood mononuclear cells depleted of T cells and monocytes exclude the quantitative deficiency of monocytes which is found in the peripheral blood of most leukemic patients as an explanation. The present results with chronic lymphocytic leukemia cells indicate that the mere expression of the Ia-like antigens by cell populations does not render them effective stimulators. The accumulated evidence obtained indicate that abnormalities, particularly of membrane function and metabolism, known to occur in chronic lymphocytic leukemia lymphocytes may be involved in the poor stimulatory capacity of the leukemic B cells.", "contents": "Poor mixed lymphocyte reaction stimulatory capacity of leukemic B cells of chronic lymphocytic leukemia patients despite the presence of Ia antigens. The human Ia-like antigens, selectively expressed on B lymphocytes, are now recognized to be closely associated with, or identical to, the gene products of the major histocompatibility complex responsible for stimulation in the mixed lymphocyte reaction. The leukemic B lymphocytes of patients with chronic lymphocytic leukemia express these antigens very well. In the present study they were readily detected by several techniques utilizing both allo- and heteroantisera. However, the leukemic B cells from most patients were found to be extremely poor stimulating cells in the mixed lymphocyte reaction. This was particularly apparent when comparisons were made on a B-cell basis with isolated normal B lymphocytes. Leukemic cell death, abnormal kinetics of leukemic cell-mediated stimulation, and serum or cellular suppressor factors do not appear to explain these findings. Studies comparing cells from a leukemic patient with those of her HLA identical sibling and results of mixed lymphocyte reactions between normal and leukemic subjects discordant for D-region-associated Ia antigens ruled out genetic explanations for the differences observed. Experiments with normal peripheral blood mononuclear cells depleted of T cells and monocytes exclude the quantitative deficiency of monocytes which is found in the peripheral blood of most leukemic patients as an explanation. The present results with chronic lymphocytic leukemia cells indicate that the mere expression of the Ia-like antigens by cell populations does not render them effective stimulators. The accumulated evidence obtained indicate that abnormalities, particularly of membrane function and metabolism, known to occur in chronic lymphocytic leukemia lymphocytes may be involved in the poor stimulatory capacity of the leukemic B cells."} {"id": "PMID:159312", "title": "Studies of immune functions of patients with systemic lupus erythematosus. T-cell subsets and antibodies to T-cell subsets.", "content": "Antibodies to T cells present in the plasma of patients with active systemic lupus erythematosus (SLE) plus complement are able to eliminate concanavalin A-induced suppressor function for the proliferative responses of T cells to allogeneic lymphocytes (MLR) and of B cells to pokeweed mitogen (PWM). Such antibodies were found to be effective in eliminating suppressor function only when T cells were treated before activation; there was no effect when treatment was performed after activation. These studies indicate that the antibodies preferentially interact with a T cell necessary for the generation of suppressor cells, rather than with mature, activated suppressor cells. Studies of individual SLE patients indicate that the same defects observed in SLE T cells were induced in normal T cells by plasma from that patient. Such observations suggest that many T-cell defects associated with active SLE may not be intrinsic T-cell abnormalities, but, rather, secondary effects of anti-T-cell antibodies. Studies of the T-cell subpopulations responsible for suppression of the MLR and PWM responses indicate that only T gamma cells (T cells bearing receptors for the Fc portion of immunoglobulin [Ig]G) acted as precursors of suppressor cells for the MLR, whereas both T gamma and T non-gamma cells (T cells not bearing receptors for the Fc portion of IgG) could be activated to suppress the PWM response. Consistent with this observation, SLE anti-T-cell antibodies that preferentially killed T gamma cells preferentially eliminated suppressor cells for the MLR.", "contents": "Studies of immune functions of patients with systemic lupus erythematosus. T-cell subsets and antibodies to T-cell subsets. Antibodies to T cells present in the plasma of patients with active systemic lupus erythematosus (SLE) plus complement are able to eliminate concanavalin A-induced suppressor function for the proliferative responses of T cells to allogeneic lymphocytes (MLR) and of B cells to pokeweed mitogen (PWM). Such antibodies were found to be effective in eliminating suppressor function only when T cells were treated before activation; there was no effect when treatment was performed after activation. These studies indicate that the antibodies preferentially interact with a T cell necessary for the generation of suppressor cells, rather than with mature, activated suppressor cells. Studies of individual SLE patients indicate that the same defects observed in SLE T cells were induced in normal T cells by plasma from that patient. Such observations suggest that many T-cell defects associated with active SLE may not be intrinsic T-cell abnormalities, but, rather, secondary effects of anti-T-cell antibodies. Studies of the T-cell subpopulations responsible for suppression of the MLR and PWM responses indicate that only T gamma cells (T cells bearing receptors for the Fc portion of immunoglobulin [Ig]G) acted as precursors of suppressor cells for the MLR, whereas both T gamma and T non-gamma cells (T cells not bearing receptors for the Fc portion of IgG) could be activated to suppress the PWM response. Consistent with this observation, SLE anti-T-cell antibodies that preferentially killed T gamma cells preferentially eliminated suppressor cells for the MLR."} {"id": "PMID:159313", "title": "Effect of fasting and streptozotocin diabetes on insulin binding and action in the isolated mouse soleus muscle.", "content": "To investigate whether skeletal muscle is resistant to insulin in insulinopenic states, insulin binding and biological effects on glucose utilization were studied in isolated soleus muscles from 24- or 48-h-fasted mice and from streptozotocin-diabetic mice. Both 48-h fasting and diabetes led to an increase in insulin binding at insulin concentrations <3.4 nM. In both states, submaximal concentrations of insulin were also more effective in stimulating muscle 2-deoxyglucose uptake and glycogen synthesis, and in activating glycogen synthase. This resulted in a two- to fourfold leftward shift in the insulin dose-response curves in muscles from both groups compared with control. No change in insulin binding or biological effects was detected in muscles from 24-h-fasted mice. Maximal insulin effectiveness on 2-deoxyglucose uptake and glycolysis was either unchanged or only slightly enhanced in 48-h-fasted mice and in diabetic animals, compared with controls. Maximal insulin effects on glycogen synthesis and glycogen synthase activation were unaltered by fasting or diabetes. Basal glucose uptake and glycolysis were similar in all groups of mice. In conclusion, when soleus muscles from 48-h-fasted mice and from diabetic mice are compared with controls it can be observed that, (a) at low insulin concentrations insulin binding is increased and insulin effectiveness in stimulating glucose transport and metabolism is enhanced; (b) biological responses to maximally effective insulin concentrations are either unaltered or slightly increased; (c) basal rates of glucose transport and metabolism are essentially unaltered. These results indicate that in insulinopenic states soleus muscle is not insulin resistant in vitro but is hypersensitive to low concentrations of insulin, and normally responsive to maximally effective doses of the hormone.", "contents": "Effect of fasting and streptozotocin diabetes on insulin binding and action in the isolated mouse soleus muscle. To investigate whether skeletal muscle is resistant to insulin in insulinopenic states, insulin binding and biological effects on glucose utilization were studied in isolated soleus muscles from 24- or 48-h-fasted mice and from streptozotocin-diabetic mice. Both 48-h fasting and diabetes led to an increase in insulin binding at insulin concentrations <3.4 nM. In both states, submaximal concentrations of insulin were also more effective in stimulating muscle 2-deoxyglucose uptake and glycogen synthesis, and in activating glycogen synthase. This resulted in a two- to fourfold leftward shift in the insulin dose-response curves in muscles from both groups compared with control. No change in insulin binding or biological effects was detected in muscles from 24-h-fasted mice. Maximal insulin effectiveness on 2-deoxyglucose uptake and glycolysis was either unchanged or only slightly enhanced in 48-h-fasted mice and in diabetic animals, compared with controls. Maximal insulin effects on glycogen synthesis and glycogen synthase activation were unaltered by fasting or diabetes. Basal glucose uptake and glycolysis were similar in all groups of mice. In conclusion, when soleus muscles from 48-h-fasted mice and from diabetic mice are compared with controls it can be observed that, (a) at low insulin concentrations insulin binding is increased and insulin effectiveness in stimulating glucose transport and metabolism is enhanced; (b) biological responses to maximally effective insulin concentrations are either unaltered or slightly increased; (c) basal rates of glucose transport and metabolism are essentially unaltered. These results indicate that in insulinopenic states soleus muscle is not insulin resistant in vitro but is hypersensitive to low concentrations of insulin, and normally responsive to maximally effective doses of the hormone."} {"id": "PMID:159314", "title": "Suppression of immune complex vasculitis in rats by prostaglandin.", "content": "Immune complex-induced vascular damage can be markedly suppressed by treatment of rats with either prostaglandin (PG)E1 or its stable derivative, 15-(S)-15-methyl PGE1, but not with PGF2 alpha. In addition, PGD2 and PGE2 also show suppressive effects. The PGE1 derivative is considerably more effective than PGE1 and shows potent anti-inflammatory activity even after oral administration. Suppression of the vasculitis reaction is reflected by a greatly diminished increase in vasopermeability, indicating little or no vascular damage. In suppressed animals, the infiltration of neutrophils is greatly reduced, and those leukocytes that have appeared at tissue sites fail to show phagocytic uptake of immune complexes. In suppressed animals, the skin sites nevertheless show deposits of immune complexes and C3 fixation in vascular walls. Neutrophils harvested from the blood of rats treated with PGE1 show depressed responsiveness in chemotaxis and in enzyme secretion after incubation with chemotactic peptide. These studies indicate that certain PG have potent anti-inflammatory activity, which may be related to their effects on leukocytes.", "contents": "Suppression of immune complex vasculitis in rats by prostaglandin. Immune complex-induced vascular damage can be markedly suppressed by treatment of rats with either prostaglandin (PG)E1 or its stable derivative, 15-(S)-15-methyl PGE1, but not with PGF2 alpha. In addition, PGD2 and PGE2 also show suppressive effects. The PGE1 derivative is considerably more effective than PGE1 and shows potent anti-inflammatory activity even after oral administration. Suppression of the vasculitis reaction is reflected by a greatly diminished increase in vasopermeability, indicating little or no vascular damage. In suppressed animals, the infiltration of neutrophils is greatly reduced, and those leukocytes that have appeared at tissue sites fail to show phagocytic uptake of immune complexes. In suppressed animals, the skin sites nevertheless show deposits of immune complexes and C3 fixation in vascular walls. Neutrophils harvested from the blood of rats treated with PGE1 show depressed responsiveness in chemotaxis and in enzyme secretion after incubation with chemotactic peptide. These studies indicate that certain PG have potent anti-inflammatory activity, which may be related to their effects on leukocytes."} {"id": "PMID:159315", "title": "Induction of suppressor activity in the autologous mixed lymphocyte reaction and in cultures with concanavalin A.", "content": "T lymphocytes that are activated in the autologous mixed lymphocyte reaction (MLR) have suppressor activity. Concanavalin A (Con A) augments the suppressor activity generated in cultures containing both T and non-T lymphocytes and can induce suppressor activity in T-lymphocyte preparations that contain too few (10%) non-T cells to generate a significant autologous MLR. However, when such T-lymphocyte preparations are further depleted of adherent cells and contain less than 2% non-T cells, Con A fails to induce suppressor activity. These findings support the concept that an autologous MLR may play an important role in generation of suppressor cells by Con A.", "contents": "Induction of suppressor activity in the autologous mixed lymphocyte reaction and in cultures with concanavalin A. T lymphocytes that are activated in the autologous mixed lymphocyte reaction (MLR) have suppressor activity. Concanavalin A (Con A) augments the suppressor activity generated in cultures containing both T and non-T lymphocytes and can induce suppressor activity in T-lymphocyte preparations that contain too few (10%) non-T cells to generate a significant autologous MLR. However, when such T-lymphocyte preparations are further depleted of adherent cells and contain less than 2% non-T cells, Con A fails to induce suppressor activity. These findings support the concept that an autologous MLR may play an important role in generation of suppressor cells by Con A."} {"id": "PMID:159316", "title": "Importance of hepatic portal circulation for insulin action in streptozotocin-diabetic rats transplanted with fetal pancreases.", "content": "The importance of the hepatic portal circulation in the response to insulin was assessed in streptozotocin-diabetic rats transplanted with syngeneic fetal pancreases. Partial reversal of diabetes was accomplished by transplantation of two or three fetal pancreases beneath the capsule of the kidney; complete reversal followed shunting of the venous drainage from the transplants to the liver. Plasma glucose after streptozotocin of 509+/-31 mg/dl (mean+/-SEM) fell after transplantation to 395+/-23 and after the shunt to 143+/-5 mg/dl. Urine volume fell from 84+/-4 to 50+/-5 ml/d and then to normal (17+/-1 ml/d) after the shunt. Glucose excretion which was 8.1+/-0.3 g/d after streptozotocin fell after transplantation to 4.8+/-0.3 g/d and after the shunt completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50+/-0.07%/min in untreated diabetes, increased to 1.39+/-0.38%/min after transplantation and to 2.52+/-0.31%/min after the shunt, not different from normal controls (2.79+/-0.25). Plasma immunoreactive insulin (IRI) was below normal (25-35 muU/ml) and unresponsive to glucose in untreated diabetic rats. After transplantation IRI levels ranged from 73-223 muU/ml and there was no rise after glucose injection. After the shunt both the basal IRI (36+/-5 muU/ml) and the peak response to glucose at 10 min (58+/-7 muU/ml) were the same as in normal controls (42+/-4 and 62+/-7 muU/ml, respectively). The fall in IRI after the shunt is explained by increased extraction of insulin passing into the liver and also diminished secretion. After removal of the transplants plasma glucose and urine values returned almost to pretransplant levels. Secretion of insulin by transplanted pancreases into the liver enhances the effectiveness probably by increased extraction and action and reveals the importance of the normal route for insulin delivery.", "contents": "Importance of hepatic portal circulation for insulin action in streptozotocin-diabetic rats transplanted with fetal pancreases. The importance of the hepatic portal circulation in the response to insulin was assessed in streptozotocin-diabetic rats transplanted with syngeneic fetal pancreases. Partial reversal of diabetes was accomplished by transplantation of two or three fetal pancreases beneath the capsule of the kidney; complete reversal followed shunting of the venous drainage from the transplants to the liver. Plasma glucose after streptozotocin of 509+/-31 mg/dl (mean+/-SEM) fell after transplantation to 395+/-23 and after the shunt to 143+/-5 mg/dl. Urine volume fell from 84+/-4 to 50+/-5 ml/d and then to normal (17+/-1 ml/d) after the shunt. Glucose excretion which was 8.1+/-0.3 g/d after streptozotocin fell after transplantation to 4.8+/-0.3 g/d and after the shunt completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50+/-0.07%/min in untreated diabetes, increased to 1.39+/-0.38%/min after transplantation and to 2.52+/-0.31%/min after the shunt, not different from normal controls (2.79+/-0.25). Plasma immunoreactive insulin (IRI) was below normal (25-35 muU/ml) and unresponsive to glucose in untreated diabetic rats. After transplantation IRI levels ranged from 73-223 muU/ml and there was no rise after glucose injection. After the shunt both the basal IRI (36+/-5 muU/ml) and the peak response to glucose at 10 min (58+/-7 muU/ml) were the same as in normal controls (42+/-4 and 62+/-7 muU/ml, respectively). The fall in IRI after the shunt is explained by increased extraction of insulin passing into the liver and also diminished secretion. After removal of the transplants plasma glucose and urine values returned almost to pretransplant levels. Secretion of insulin by transplanted pancreases into the liver enhances the effectiveness probably by increased extraction and action and reveals the importance of the normal route for insulin delivery."} {"id": "PMID:159318", "title": "Cell-mediated cytotoxic responses of spleen cells from mice bearing primary, chemically induced tumors.", "content": "Sarcomas were induced in C57BL/6 mice by using 3-methylcholanthrene. Spleen cells taken from these mice bearing primary, chemically induced tumors and from matched control mice were assessed for the capacity to generate cell-mediated cytotoxic cell activity after in vitro sensitization. Spleen cells from tumor-bearing mice generated strong cell-mediated cytotoxic responses against alloantigens and antigens on syngeneic cells.", "contents": "Cell-mediated cytotoxic responses of spleen cells from mice bearing primary, chemically induced tumors. Sarcomas were induced in C57BL/6 mice by using 3-methylcholanthrene. Spleen cells taken from these mice bearing primary, chemically induced tumors and from matched control mice were assessed for the capacity to generate cell-mediated cytotoxic cell activity after in vitro sensitization. Spleen cells from tumor-bearing mice generated strong cell-mediated cytotoxic responses against alloantigens and antigens on syngeneic cells."} {"id": "PMID:159319", "title": "Cell-mediated lympholysis by human maternal and neonatal lymphocytes: mother's reactivity against neonatal cells and vice versa.", "content": "Maternal reactivity in cell-mediated lympholysis (CML) against cells from her own child is, in average, half of the maternal reactivity against unrelated adult cells. This finding remains the same when cells from a newborn or from an older child are used, suggesting that the reduced maternal reactivity is based rather on the one haplotype identity between the mother and child than on the occurrence of specific maternal tolerance. Consistently, CML-capacity of the child, directed against cells of own mother, is half of the control values, again independently of the child's age.", "contents": "Cell-mediated lympholysis by human maternal and neonatal lymphocytes: mother's reactivity against neonatal cells and vice versa. Maternal reactivity in cell-mediated lympholysis (CML) against cells from her own child is, in average, half of the maternal reactivity against unrelated adult cells. This finding remains the same when cells from a newborn or from an older child are used, suggesting that the reduced maternal reactivity is based rather on the one haplotype identity between the mother and child than on the occurrence of specific maternal tolerance. Consistently, CML-capacity of the child, directed against cells of own mother, is half of the control values, again independently of the child's age."} {"id": "PMID:159320", "title": "Sex-related immunocompetence of BALB/c mice. I. Study of immunologic responsiveness of neonatal, weanling, and young adult mice.", "content": "The responses of lymphoid cells from the thymus, lymph nodes, and spleen of male and female BALB/c mice were evaluated to determine if sex-related variations in immune expression could be found. Immunologic assays used included blastogenic responses to mitogens, mixed lymphocyte responses, and direct and indirect measurement of plaque-forming cells against soluble and particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Little or no differences between the sexes were observed in the mitogenesis of lymph nodes and thymuses. Newborn mice did not demonstrate the sex-associated immune differences. Among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed.", "contents": "Sex-related immunocompetence of BALB/c mice. I. Study of immunologic responsiveness of neonatal, weanling, and young adult mice. The responses of lymphoid cells from the thymus, lymph nodes, and spleen of male and female BALB/c mice were evaluated to determine if sex-related variations in immune expression could be found. Immunologic assays used included blastogenic responses to mitogens, mixed lymphocyte responses, and direct and indirect measurement of plaque-forming cells against soluble and particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Little or no differences between the sexes were observed in the mitogenesis of lymph nodes and thymuses. Newborn mice did not demonstrate the sex-associated immune differences. Among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed."} {"id": "PMID:159321", "title": "Lyt phenotypes of responding cells in secondary alloantigen responses.", "content": "Lymphocytes responding in a \"secondary\" MLC-CML system, after in vitro sensitization, apparently fall into two classes with regard to their Lyt phenotype. First, are the cells that form the majority of the proliferating cells after restimulation with either I or K + I differences, which are Lyt 1-2, and second, are Tc that are Lyt 1-2+. The Lyt 1-2- proliferating cells are not cytotoxic and are lysed by treatment with anti-Thy 1.2 serum in the presence of C.", "contents": "Lyt phenotypes of responding cells in secondary alloantigen responses. Lymphocytes responding in a \"secondary\" MLC-CML system, after in vitro sensitization, apparently fall into two classes with regard to their Lyt phenotype. First, are the cells that form the majority of the proliferating cells after restimulation with either I or K + I differences, which are Lyt 1-2, and second, are Tc that are Lyt 1-2+. The Lyt 1-2- proliferating cells are not cytotoxic and are lysed by treatment with anti-Thy 1.2 serum in the presence of C."} {"id": "PMID:159323", "title": "Regulation of the murine IgE antibody response. I. Characterization of suppressor cells regulating both persistent and transient responses and their sensitivity to low doses of X-irradiation.", "content": "Anti-ovalbumin (OA) IgE antibody responses were measured in B6D2F1 mice as a function of time and antigen dose. One hundred to 200 microgram of OA in Al(OH)3 elicited transient responses, whereas 1 to 10 microgram of OA in Al(OH)3 elicited persistent anti-OA IgE responses of high titer. T cells isolated from the spleens of mice mounting either a persistent or a transient response strongly suppressed primary anti-DNP IgE responses in unirradiated recipient mice that were immunized with DNP-OA in Al(OH)3; it was, therefore, concluded that suppressor T cells (Ts cells) were activated during both the persistent and transient IgE responses. Nevertheless, in the present study it was not possible to completely rule out the contention that IgG antibodies may also have been suppressing the IgE response. With a modified adoptive transfer system, it was shown that these Ts cells were sensitive to low doses (250 R) of x-irradiation. The suppressive activity of long-term OA primed cells was also shown to be markedly enhanced when cultured for 24 hr with soluble OA; this finding was interpreted to indicate the presence of memory suppressor cells.", "contents": "Regulation of the murine IgE antibody response. I. Characterization of suppressor cells regulating both persistent and transient responses and their sensitivity to low doses of X-irradiation. Anti-ovalbumin (OA) IgE antibody responses were measured in B6D2F1 mice as a function of time and antigen dose. One hundred to 200 microgram of OA in Al(OH)3 elicited transient responses, whereas 1 to 10 microgram of OA in Al(OH)3 elicited persistent anti-OA IgE responses of high titer. T cells isolated from the spleens of mice mounting either a persistent or a transient response strongly suppressed primary anti-DNP IgE responses in unirradiated recipient mice that were immunized with DNP-OA in Al(OH)3; it was, therefore, concluded that suppressor T cells (Ts cells) were activated during both the persistent and transient IgE responses. Nevertheless, in the present study it was not possible to completely rule out the contention that IgG antibodies may also have been suppressing the IgE response. With a modified adoptive transfer system, it was shown that these Ts cells were sensitive to low doses (250 R) of x-irradiation. The suppressive activity of long-term OA primed cells was also shown to be markedly enhanced when cultured for 24 hr with soluble OA; this finding was interpreted to indicate the presence of memory suppressor cells."} {"id": "PMID:159324", "title": "The Qa-2 antigen on lymphocyte subpopulations. Mixed lymphocyte culture and cell-mediated lympholysis.", "content": "Treatments of spleen cells from Qa-2+ strains with Qa-2 antiserum plus complement (C) have revealed that the Qa-2 antigen is present on restricted functional lymphocyte subpopulations. Anti-Qa-2 plus C reduced the mixed lymphocyte culture response and inhibited the generation of cytolytic effector cells. This treatment, however, did not affect cytolytic effector cells once they were generated.", "contents": "The Qa-2 antigen on lymphocyte subpopulations. Mixed lymphocyte culture and cell-mediated lympholysis. Treatments of spleen cells from Qa-2+ strains with Qa-2 antiserum plus complement (C) have revealed that the Qa-2 antigen is present on restricted functional lymphocyte subpopulations. Anti-Qa-2 plus C reduced the mixed lymphocyte culture response and inhibited the generation of cytolytic effector cells. This treatment, however, did not affect cytolytic effector cells once they were generated."} {"id": "PMID:159327", "title": "[The topographical localization of spinal motoneurons of the rat and its numerical alternation in regard to development (author's transl)].", "content": "The topographical localization of spinal motoneurons innervating the forelimb muscles of the rat and its numerical alternation in regard to development was observed by HRP (horseradish peroxidase) method. HRP method is a histochemical technique to trace the cellular origin of axon terminal net work. When HRP is injected into the muscles, the enzyme is taken up by nerve endings and transported retrogradely by the axoplamic flow to the original cell body, and does not transported hematogenously and does not cross the synapse. The spinal motoneurons were found in spindle-shape longitudinal cell columns according to its innervation. The motoneurons supplying the biceps brachii muscle were located in the dorso-lateral nucleus on the anterior horn of the 4th cervical segment, and extended downward to the ventral nucleus in 8th cervical segment, forming a spindle-shape cell column. The thick spindle-shape cell column consisting of cells which innervated the triceps brachii muscle lied in the ventro-medial nucleus of the 6th, 7th and 8th cervical segment. The neurons innervating the flexor carpi ulnaris muscle were located in 7th and 8th cervical segment, but few in number compared to those of the biceps and triceps. The motoneurons innervating the biceps brachii muscle decreased in number with increasing age according to exponential curve. The total number of HRP-labeled neurons in two week old rat ranged from 2,932 to 2,017 and markedly decreased during first eight weeks, in eight week old rat ranged from 1,637 to 603. After this, they gradually decreased to 312 in 50 weeks on an average, where the number corresponded to about 13% of those of two week old rat. The data indicate that ventral horn has a great deal of excess neurons which has a distinct neuromuscular connection as suggested by Prestige, in the developmental stage of Xenopus laevis. In young rats (ten days to two weeks of age), HRP-labeled neurons were also present in the ventral horn on the non-injected side. These large and multigonal contralateral HRP-labeled neurons constituted a characteristic feature of spinal motoneurons, and distributed through the same segment as those on injected side. The total number of HRP-labeled neurons within non-injected side ranged from 563 to 197 and corresponded from one-fifth to one-tenth of that in the injected side. In five weeks or elder rat, no HRP-labeled neurons could be observed in non-injected side. This indicates that in immature rats the muscles are innervated bilaterally by the spinal nerve, since HRP is transported by retrograde axoplasmic flow and does not cross the synapse, and the bilateral motor innervation has disappeared with maturation. The bilateral motor innervation is therefore, presumed to be an immature mode of innervation limited to the early stage of life. Although bilateral motor innervation following the nerve injury in the limb at the early stage of life has been confirmed by ourselves, the significance of the immature mode of innervation is still hard to explain.", "contents": "[The topographical localization of spinal motoneurons of the rat and its numerical alternation in regard to development (author's transl)]. The topographical localization of spinal motoneurons innervating the forelimb muscles of the rat and its numerical alternation in regard to development was observed by HRP (horseradish peroxidase) method. HRP method is a histochemical technique to trace the cellular origin of axon terminal net work. When HRP is injected into the muscles, the enzyme is taken up by nerve endings and transported retrogradely by the axoplamic flow to the original cell body, and does not transported hematogenously and does not cross the synapse. The spinal motoneurons were found in spindle-shape longitudinal cell columns according to its innervation. The motoneurons supplying the biceps brachii muscle were located in the dorso-lateral nucleus on the anterior horn of the 4th cervical segment, and extended downward to the ventral nucleus in 8th cervical segment, forming a spindle-shape cell column. The thick spindle-shape cell column consisting of cells which innervated the triceps brachii muscle lied in the ventro-medial nucleus of the 6th, 7th and 8th cervical segment. The neurons innervating the flexor carpi ulnaris muscle were located in 7th and 8th cervical segment, but few in number compared to those of the biceps and triceps. The motoneurons innervating the biceps brachii muscle decreased in number with increasing age according to exponential curve. The total number of HRP-labeled neurons in two week old rat ranged from 2,932 to 2,017 and markedly decreased during first eight weeks, in eight week old rat ranged from 1,637 to 603. After this, they gradually decreased to 312 in 50 weeks on an average, where the number corresponded to about 13% of those of two week old rat. The data indicate that ventral horn has a great deal of excess neurons which has a distinct neuromuscular connection as suggested by Prestige, in the developmental stage of Xenopus laevis. In young rats (ten days to two weeks of age), HRP-labeled neurons were also present in the ventral horn on the non-injected side. These large and multigonal contralateral HRP-labeled neurons constituted a characteristic feature of spinal motoneurons, and distributed through the same segment as those on injected side. The total number of HRP-labeled neurons within non-injected side ranged from 563 to 197 and corresponded from one-fifth to one-tenth of that in the injected side. In five weeks or elder rat, no HRP-labeled neurons could be observed in non-injected side. This indicates that in immature rats the muscles are innervated bilaterally by the spinal nerve, since HRP is transported by retrograde axoplasmic flow and does not cross the synapse, and the bilateral motor innervation has disappeared with maturation. The bilateral motor innervation is therefore, presumed to be an immature mode of innervation limited to the early stage of life. Although bilateral motor innervation following the nerve injury in the limb at the early stage of life has been confirmed by ourselves, the significance of the immature mode of innervation is still hard to explain."} {"id": "PMID:159329", "title": "Erythropoiesis and artificial blood substitution with a perfluorocarbon-polyol.", "content": "Rats were perfused with Fluosol-43, a perfluorotributylamine-pluronic F-68 emulsion, to produce hematocrits of about 6% and the mechanisms of blood cell replacement were studied. The packed RBC volume and number of RBCs per cubic millimeter increased gradually as the time after perfusion was completed until reaching the preperfusion level at about 1 week. The WBCs per cubic millimeter, which were not as severely depleted because of their vast storage compartment, increased to preperfusion levels by 24 hr and continued to increase through 7 days. Plasma did not show significant Ep activity until 48 to 72 hr after perfusion was concluded. Thus, although 90% of the RBCs were removed, elevated erythropoietin activity was not detected immediately because the perfluorocarbon compound replaced the capacity of the RBCs as an oxygen and carbon dioxide carrier.", "contents": "Erythropoiesis and artificial blood substitution with a perfluorocarbon-polyol. Rats were perfused with Fluosol-43, a perfluorotributylamine-pluronic F-68 emulsion, to produce hematocrits of about 6% and the mechanisms of blood cell replacement were studied. The packed RBC volume and number of RBCs per cubic millimeter increased gradually as the time after perfusion was completed until reaching the preperfusion level at about 1 week. The WBCs per cubic millimeter, which were not as severely depleted because of their vast storage compartment, increased to preperfusion levels by 24 hr and continued to increase through 7 days. Plasma did not show significant Ep activity until 48 to 72 hr after perfusion was concluded. Thus, although 90% of the RBCs were removed, elevated erythropoietin activity was not detected immediately because the perfluorocarbon compound replaced the capacity of the RBCs as an oxygen and carbon dioxide carrier."} {"id": "PMID:159331", "title": "Experimental IgA nephropathy.", "content": "An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.", "contents": "Experimental IgA nephropathy. An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis."} {"id": "PMID:159343", "title": "Investigation of the structure of the blue copper protein from Rhus vernicifera stellacyanin by 1H nuclear magnetic resonance spectroscopy.", "content": "The 270-MHz 1H nuclear magnetic resonance spectra of Cu(II), Cu(I), and apo-stellacyanin are reported and compared. The data indicate that little conformational change occurs on reduction of the protein or on removing the copper ion. In the aromatic region of the spectra of the holoprotein, resonances associated with two freely titrating histidines are observed. Two additional sharp resonances are observed in the spectra of the apostellacyanin which are tentatively assigned to additional histidines. This result requires that not more than two histidines can be ligands since there are only four histidines in the whole protein. The absence of methionine has been reported and is one of the possible causes for the difference between stellacyanin and the other copper blue proteins. A comparison of these data with those available for other blue copper proteins, in conjunction with the sequence information, leads to a proposed structure for the copper site in stellacyanin.", "contents": "Investigation of the structure of the blue copper protein from Rhus vernicifera stellacyanin by 1H nuclear magnetic resonance spectroscopy. The 270-MHz 1H nuclear magnetic resonance spectra of Cu(II), Cu(I), and apo-stellacyanin are reported and compared. The data indicate that little conformational change occurs on reduction of the protein or on removing the copper ion. In the aromatic region of the spectra of the holoprotein, resonances associated with two freely titrating histidines are observed. Two additional sharp resonances are observed in the spectra of the apostellacyanin which are tentatively assigned to additional histidines. This result requires that not more than two histidines can be ligands since there are only four histidines in the whole protein. The absence of methionine has been reported and is one of the possible causes for the difference between stellacyanin and the other copper blue proteins. A comparison of these data with those available for other blue copper proteins, in conjunction with the sequence information, leads to a proposed structure for the copper site in stellacyanin."} {"id": "PMID:159346", "title": "Selective effects of vibration on monosynaptic and late EMG responses in human soleus muscle after stimulation of the posterior tibial nerve or a tendon tap.", "content": "In normal subjects it was possible to evoke tendon and Hoffman reflexes which were followed by late EMG responses with a latency of 150-250 ms after the reflex stimuli. Analysis of the covariations of reflexes and late responses revealed that muscle spindle sensitivity and strength of the preceding twitch are not essential factors in determining the occurrence of the late responses as opposed to excitability changes within the spinal cord. Inhibition of monosynaptic reflexes and facilitation of late EMG responses to vibration indicate a difference in central pathways. A polysynaptic pathway may be involved in the late responses.", "contents": "Selective effects of vibration on monosynaptic and late EMG responses in human soleus muscle after stimulation of the posterior tibial nerve or a tendon tap. In normal subjects it was possible to evoke tendon and Hoffman reflexes which were followed by late EMG responses with a latency of 150-250 ms after the reflex stimuli. Analysis of the covariations of reflexes and late responses revealed that muscle spindle sensitivity and strength of the preceding twitch are not essential factors in determining the occurrence of the late responses as opposed to excitability changes within the spinal cord. Inhibition of monosynaptic reflexes and facilitation of late EMG responses to vibration indicate a difference in central pathways. A polysynaptic pathway may be involved in the late responses."} {"id": "PMID:159351", "title": "Echocardiographic abnormalities in infants of diabetic mothers.", "content": "In order to evaluate the presence of myocardial hypertrophy and/or abnormalities of postnatal cardiovascular adaptation, echocardiograms were performed on 34 infants of diabetic mothers. Based on cardiopulmonary assessment, the IDM were divided into three groups: Group I with congestive heart failure predominating: Group II with respiratory distress predominating: Group III asymptomatic. Hypertrophy of the interventricular septum and of the walls of left and right ventricles was frequently present in IDM: this change was most notable in association with clinical CHF. Six IDM, four of whom were found to have CHF, had additional echocardiographic signs of subaortic stenosis. All IDM had normal indices of left ventricular performance, despite the presence of CHE. In IDM with respiratory distress, the right ventricular pre-ejection period to ventricular ejection time ratio was elevated, suggesting an abnormality of the transitional pulmonary circulation. Poor maternal diabetes control and maternal systemic hypertension were closely correlated with evidence of myocardial hypertrophy in the infants.", "contents": "Echocardiographic abnormalities in infants of diabetic mothers. In order to evaluate the presence of myocardial hypertrophy and/or abnormalities of postnatal cardiovascular adaptation, echocardiograms were performed on 34 infants of diabetic mothers. Based on cardiopulmonary assessment, the IDM were divided into three groups: Group I with congestive heart failure predominating: Group II with respiratory distress predominating: Group III asymptomatic. Hypertrophy of the interventricular septum and of the walls of left and right ventricles was frequently present in IDM: this change was most notable in association with clinical CHF. Six IDM, four of whom were found to have CHF, had additional echocardiographic signs of subaortic stenosis. All IDM had normal indices of left ventricular performance, despite the presence of CHE. In IDM with respiratory distress, the right ventricular pre-ejection period to ventricular ejection time ratio was elevated, suggesting an abnormality of the transitional pulmonary circulation. Poor maternal diabetes control and maternal systemic hypertension were closely correlated with evidence of myocardial hypertrophy in the infants."} {"id": "PMID:159352", "title": "The natural history of hypertrophic cardiomyopathy in infants of diabetic mothers.", "content": "Eleven infants of diabetic mothers with hypertrophic cardiomyopathy have been followed for 30 to 40 months. All infants presented with cardiorespiratory distress and were found to have disproportionate septal hypertrophy on echocardiogram. Cardiac catheterization was done in four infants; three had significant subaortic obstruction. One infant had remarkable improvement after treatment with propranolol. Two infants who received digoxin did poorly and responded favorably to cessation of therapy. The natural history of HCM-IDM appears to be benign, with a resolution of symptoms within two to four weeks and a resolution of septal hypertrophy within two to 12 months. Most of the infants need only supportive care; if pharmacologic intervention is deemed necessary, propranolol appears to be the drug of choice. The natural history of this entity is that of spontaneous regression of symptoms and septal hypertrophy irrespective of therapy.", "contents": "The natural history of hypertrophic cardiomyopathy in infants of diabetic mothers. Eleven infants of diabetic mothers with hypertrophic cardiomyopathy have been followed for 30 to 40 months. All infants presented with cardiorespiratory distress and were found to have disproportionate septal hypertrophy on echocardiogram. Cardiac catheterization was done in four infants; three had significant subaortic obstruction. One infant had remarkable improvement after treatment with propranolol. Two infants who received digoxin did poorly and responded favorably to cessation of therapy. The natural history of HCM-IDM appears to be benign, with a resolution of symptoms within two to four weeks and a resolution of septal hypertrophy within two to 12 months. Most of the infants need only supportive care; if pharmacologic intervention is deemed necessary, propranolol appears to be the drug of choice. The natural history of this entity is that of spontaneous regression of symptoms and septal hypertrophy irrespective of therapy."} {"id": "PMID:159354", "title": "Fibromuscular dysplasia of renal arteries: an important cause of renovascular hypertension in children.", "content": "Fibromuscular dysplasia of renal arteries was the cause of hypertension in four consecutive children with renal artery stenosis. Two were asymptomatic, the third had had hypertension for seven years but had not been treated, and the fourth, a 9-month-old infant, presented with cardiac failure. Heart enlargement and left ventricular hypertrophy were present in all. Rapid sequence urograms demonstrated a smaller kidney and delayed appearance and disappearance of the contrast medium on the affected side in all. Angiograms showed left RAS in all. Peripheral plasma renin activity was elevated in only three of the four patients. Antihypertensive and diuretic drugs were not very effective therapeutically. Ischemia of the ipsilateral kidney probably prevented normal growth and led to shrinkage of the kidney in one patient. Following nephrectomy the BP has remained normal without any therapy for 24 to 64 months. With normalization of BP, accelerated growth ensued, the cardiomegaly regressed and the hypertensive retinopathy resolved. These patients demonstrate that: (1) FMD is an important cause of RAS. (2) the well-known radiologic feature of FMD, the beaded appearance, is usually not seen in children. (3) control of BP leads to normalization of linear growth, usually impaired in severe hypertension, and (4) target organ complications such as cardiomegaly, LVH, and hypertensive retinopathy are reversible in one to 10 months.", "contents": "Fibromuscular dysplasia of renal arteries: an important cause of renovascular hypertension in children. Fibromuscular dysplasia of renal arteries was the cause of hypertension in four consecutive children with renal artery stenosis. Two were asymptomatic, the third had had hypertension for seven years but had not been treated, and the fourth, a 9-month-old infant, presented with cardiac failure. Heart enlargement and left ventricular hypertrophy were present in all. Rapid sequence urograms demonstrated a smaller kidney and delayed appearance and disappearance of the contrast medium on the affected side in all. Angiograms showed left RAS in all. Peripheral plasma renin activity was elevated in only three of the four patients. Antihypertensive and diuretic drugs were not very effective therapeutically. Ischemia of the ipsilateral kidney probably prevented normal growth and led to shrinkage of the kidney in one patient. Following nephrectomy the BP has remained normal without any therapy for 24 to 64 months. With normalization of BP, accelerated growth ensued, the cardiomegaly regressed and the hypertensive retinopathy resolved. These patients demonstrate that: (1) FMD is an important cause of RAS. (2) the well-known radiologic feature of FMD, the beaded appearance, is usually not seen in children. (3) control of BP leads to normalization of linear growth, usually impaired in severe hypertension, and (4) target organ complications such as cardiomegaly, LVH, and hypertensive retinopathy are reversible in one to 10 months."} {"id": "PMID:159356", "title": "Autogenetic inhibition of motoneurones by impulses in group Ia muscle spindle afferents.", "content": "1. Inhibitory post-synaptic potentials evoked by adequate stimulation of group Ia muscle spindle afferents of homonymous and synergistic muscles and by selective electrical stimulation of tendon organ afferents were analysed in motoneurones of triceps surae and plantaris. 2. Selective activation of Ia afferents was verified to occur with brief stretches of triceps surae and plantaris 35 micrometer or less in amplitude with an initial muscle tension of 5 N; stretches of 30--35 micrometer were estimated to activate 80--90% of Ia afferents in these muscles. Under the same conditions the lowest thresholds for group Ib tendon organ afferents were about 40 micrometer. 3. Stretches less than or equal to 30 micrometer evoked i.p.s.p.s in 80% of triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s wef triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s were 10 micrometer or less. However, such low thresholds for stretch-evoked i.p.s.p.s, lower than the thresholds for activation of Ib afferents, were found mainly in spinalized, unanaesthetized (after decerebration) or lightly anaesthetized animals. The latencies of these i.p.s.p.s indicated disynaptic and trisynaptic coupling between Ia afferents and motoneurones. The i.p.s.p.s were evoked (i) from the homonymous and synergistic muscles stretched together, (ii) from the homonymous muscles alone and (iii) from the synergistic muscles alone. 4. Control experiments showed that i.p.s.p.s could be evoked by stretches sub-threshold for discharging motoneurones, thus showing that those i.p.s.p.s were not mediated by Renshaw cells. The stretch-evoked i.p.s.p.s disappeared after sectioning the nerves from the corresponding muscles, further excluding their mediation by afferents other than group Ia afferents from thf stretched muscle. 5. In order to selectively activate tendon organ afferents, thresholds for excitation of Ia afferents by electrical stimuli were increased to a level above the threshold for Ib afferents by prolonged muscle vibration (Coppin, Jack & MacLennan, 1970). I.p.s.p.s evoked by stimuli near threshold for Ib afferents appeared with latencies indicating disynaptic coupling. Later (trisynaptic) components of Ib i.p.s.p.s required somewhat stronger stimuli. 6. Amplitudes of Ia i.p.s.p.s evoked by muscle stretches activating about 80% of muscle spindle afferents were compared with amplitudes of Ib i.p.s.p.s due to less than 50% of tendon organ afferents of the same muscles. The Ia i.p.s.p.s were much smaller (16--35%) than the Ib i.p.s.p.s. The amplitudes of such Ia and Ib i.p.s.p.s constituted about 10 and 25--66%, respectively, of the maximal i.p.s.p.s evoked by electrical stimulation of all group I afferents. 7. We conclude that inhibition of motoneurones may be evoked from Ia muscle spindle afferents from homonymous and synergistic muscles as well as from Ib tendon organ afferents...", "contents": "Autogenetic inhibition of motoneurones by impulses in group Ia muscle spindle afferents. 1. Inhibitory post-synaptic potentials evoked by adequate stimulation of group Ia muscle spindle afferents of homonymous and synergistic muscles and by selective electrical stimulation of tendon organ afferents were analysed in motoneurones of triceps surae and plantaris. 2. Selective activation of Ia afferents was verified to occur with brief stretches of triceps surae and plantaris 35 micrometer or less in amplitude with an initial muscle tension of 5 N; stretches of 30--35 micrometer were estimated to activate 80--90% of Ia afferents in these muscles. Under the same conditions the lowest thresholds for group Ib tendon organ afferents were about 40 micrometer. 3. Stretches less than or equal to 30 micrometer evoked i.p.s.p.s in 80% of triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s wef triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s were 10 micrometer or less. However, such low thresholds for stretch-evoked i.p.s.p.s, lower than the thresholds for activation of Ib afferents, were found mainly in spinalized, unanaesthetized (after decerebration) or lightly anaesthetized animals. The latencies of these i.p.s.p.s indicated disynaptic and trisynaptic coupling between Ia afferents and motoneurones. The i.p.s.p.s were evoked (i) from the homonymous and synergistic muscles stretched together, (ii) from the homonymous muscles alone and (iii) from the synergistic muscles alone. 4. Control experiments showed that i.p.s.p.s could be evoked by stretches sub-threshold for discharging motoneurones, thus showing that those i.p.s.p.s were not mediated by Renshaw cells. The stretch-evoked i.p.s.p.s disappeared after sectioning the nerves from the corresponding muscles, further excluding their mediation by afferents other than group Ia afferents from thf stretched muscle. 5. In order to selectively activate tendon organ afferents, thresholds for excitation of Ia afferents by electrical stimuli were increased to a level above the threshold for Ib afferents by prolonged muscle vibration (Coppin, Jack & MacLennan, 1970). I.p.s.p.s evoked by stimuli near threshold for Ib afferents appeared with latencies indicating disynaptic coupling. Later (trisynaptic) components of Ib i.p.s.p.s required somewhat stronger stimuli. 6. Amplitudes of Ia i.p.s.p.s evoked by muscle stretches activating about 80% of muscle spindle afferents were compared with amplitudes of Ib i.p.s.p.s due to less than 50% of tendon organ afferents of the same muscles. The Ia i.p.s.p.s were much smaller (16--35%) than the Ib i.p.s.p.s. The amplitudes of such Ia and Ib i.p.s.p.s constituted about 10 and 25--66%, respectively, of the maximal i.p.s.p.s evoked by electrical stimulation of all group I afferents. 7. We conclude that inhibition of motoneurones may be evoked from Ia muscle spindle afferents from homonymous and synergistic muscles as well as from Ib tendon organ afferents..."} {"id": "PMID:159361", "title": "Unique leukemic non-T/non-B lymphoid cell lines (REH and KM-3): absence of MLR-S and presence of suppressor cell activity for normal T-cell response.", "content": "The present study unequivocally demonstrates that leukemic non-T/non-B lymphod cells from three cell lines (NALL-1, NALM-6 and NALM-16) possess a strong stimulating capacity in \"one-way\" mixed lymphocyte reaction (MLR-S), while leukemic cells from two non-T/non-B cell lines (REH and KM-3) possess no MLR-S. It is speculated that leukemic non-T/non-B lymphoid cells with MLR-S may represent less differentiated leukemic B cells and leukemic non-T/B lymphoid cells without MLR-S may represent less differentiated leukemic T cells. The REH or KM-3 cells without MLR-S also act as suppressor cells on normal T lymphocyte response to mitogen and allogeneic cells by secreting a potent suppressor activity. The MOLT-4 leukemic T lymphoid cells with no MLR-S, on the other hand, do not act as suppressor cells on T lymphocyte response. The soluble factor(s) secreted by the REH or KM-3 cell line is non-toxic to T lymphocytes and heat-sensitive. A significant suppression of T lymphocyte response is still observed, even when the active material is only present for one hour prior to the addition of PHA or it is added several days after the beginning of cultures. The biological and physico-chemical nature of this active material has not been defined. Further studies are currently in progress for biological and physico-chemical characterization and isolation of the active material.", "contents": "Unique leukemic non-T/non-B lymphoid cell lines (REH and KM-3): absence of MLR-S and presence of suppressor cell activity for normal T-cell response. The present study unequivocally demonstrates that leukemic non-T/non-B lymphod cells from three cell lines (NALL-1, NALM-6 and NALM-16) possess a strong stimulating capacity in \"one-way\" mixed lymphocyte reaction (MLR-S), while leukemic cells from two non-T/non-B cell lines (REH and KM-3) possess no MLR-S. It is speculated that leukemic non-T/non-B lymphoid cells with MLR-S may represent less differentiated leukemic B cells and leukemic non-T/B lymphoid cells without MLR-S may represent less differentiated leukemic T cells. The REH or KM-3 cells without MLR-S also act as suppressor cells on normal T lymphocyte response to mitogen and allogeneic cells by secreting a potent suppressor activity. The MOLT-4 leukemic T lymphoid cells with no MLR-S, on the other hand, do not act as suppressor cells on T lymphocyte response. The soluble factor(s) secreted by the REH or KM-3 cell line is non-toxic to T lymphocytes and heat-sensitive. A significant suppression of T lymphocyte response is still observed, even when the active material is only present for one hour prior to the addition of PHA or it is added several days after the beginning of cultures. The biological and physico-chemical nature of this active material has not been defined. Further studies are currently in progress for biological and physico-chemical characterization and isolation of the active material."} {"id": "PMID:159362", "title": "Characteristics of peritoneal lymphocytes from New Zealand Black and normal mice autoreactive for mouse erythrocytes.", "content": "New Zealand Black mice spontaneously develop autoimmune hemolytic anemia. Peritoneal cavity lymphocytes from NZB mice include a high proportion of cells that bind autologous erythrocytes. These cells produce ani-erythrocyte antibody that can be demonstrated when target erythrocytes are treated with bromelin. Such autoreactive cells are also present in normal mice, though in much smaller numbers. Aging and sex influence the peritoneal anti-erythrocyte response to bromelin-treated mouse erythrocytes. Older mice generally produce more rosettes and plaques than younger animals, and females have higher responses than males. During short-term culture in the absence of antigen, the response to bromelin-treated mouse erythrocytes increases. By contrast, the response to untreated mouse erythrocytes decreases during the same culture conditions. The in vitro response to bromelin-treated mouse erythrocytes by New Zealand Black peritoneal lymphocytes is suppressed by a cell that binds to untreated erythrocytes. The enhanced response to bromelin-treated mouse erythrocytes in culture may reflect the loss of this suppressor cell.", "contents": "Characteristics of peritoneal lymphocytes from New Zealand Black and normal mice autoreactive for mouse erythrocytes. New Zealand Black mice spontaneously develop autoimmune hemolytic anemia. Peritoneal cavity lymphocytes from NZB mice include a high proportion of cells that bind autologous erythrocytes. These cells produce ani-erythrocyte antibody that can be demonstrated when target erythrocytes are treated with bromelin. Such autoreactive cells are also present in normal mice, though in much smaller numbers. Aging and sex influence the peritoneal anti-erythrocyte response to bromelin-treated mouse erythrocytes. Older mice generally produce more rosettes and plaques than younger animals, and females have higher responses than males. During short-term culture in the absence of antigen, the response to bromelin-treated mouse erythrocytes increases. By contrast, the response to untreated mouse erythrocytes decreases during the same culture conditions. The in vitro response to bromelin-treated mouse erythrocytes by New Zealand Black peritoneal lymphocytes is suppressed by a cell that binds to untreated erythrocytes. The enhanced response to bromelin-treated mouse erythrocytes in culture may reflect the loss of this suppressor cell."} {"id": "PMID:159363", "title": "Unusual modification of bacteriophage Mu DNA.", "content": "Bacteriophage Mu DNA was labeled after induction in the presence of [2-(3)H]adenine or [8-(3)H]adenine. Both Mu mom(+).dam(+) DNA and Mu mom(-).dam(+) DNA have similar N(6)-methyladenine (MeAde) contents, as well as similar frequencies of MeAde nearest neighbors. Both DNAs are sensitive to in vitro cleavage by R.DpnI but resistant to cleavage by R.DpnII. These results indicate that the mom(+) protein does not alter the sequence specificity of the host dam(+) methylase to produce MeAde at new sites. However, we have discovered a new modified base, denoted A(x), in Mu mom(+).dam(+) DNA; approximately 15% of the adenine residues are modified to A(x). Although the precise nature of the modification is not yet defined, analysis by electrophoresis and chromatography indicates that the N(6)-amino group is not the site of modification, and that the added moiety contains a free carboxyl group. A(x) is not present in Mu mom(+).dam(+) or Mu mom(-).dam(+) phage DNA or in cellular DNA from uninduced Mu mom(+).dam(+) lysogens. These results suggest that expression of the dam(+) and mom(+) genes are required for the A(x) modification and that this modification is responsible for protecting Mu DNA against certain restriction nucleases. Mu mom(+).dam(-) DNA and Mu mom(-).dam(-) DNA contain a very low level of MeAde (ca. 1 MeAde per 5,000 adenine residues). Since the only nearest neighbor to MeAde appears to be cytosine, we suggest that the methylated sequence is 5'... C-A(*)-C... 3' and that this methylation is mediated by the EcoK modification enzyme.", "contents": "Unusual modification of bacteriophage Mu DNA. Bacteriophage Mu DNA was labeled after induction in the presence of [2-(3)H]adenine or [8-(3)H]adenine. Both Mu mom(+).dam(+) DNA and Mu mom(-).dam(+) DNA have similar N(6)-methyladenine (MeAde) contents, as well as similar frequencies of MeAde nearest neighbors. Both DNAs are sensitive to in vitro cleavage by R.DpnI but resistant to cleavage by R.DpnII. These results indicate that the mom(+) protein does not alter the sequence specificity of the host dam(+) methylase to produce MeAde at new sites. However, we have discovered a new modified base, denoted A(x), in Mu mom(+).dam(+) DNA; approximately 15% of the adenine residues are modified to A(x). Although the precise nature of the modification is not yet defined, analysis by electrophoresis and chromatography indicates that the N(6)-amino group is not the site of modification, and that the added moiety contains a free carboxyl group. A(x) is not present in Mu mom(+).dam(+) or Mu mom(-).dam(+) phage DNA or in cellular DNA from uninduced Mu mom(+).dam(+) lysogens. These results suggest that expression of the dam(+) and mom(+) genes are required for the A(x) modification and that this modification is responsible for protecting Mu DNA against certain restriction nucleases. Mu mom(+).dam(-) DNA and Mu mom(-).dam(-) DNA contain a very low level of MeAde (ca. 1 MeAde per 5,000 adenine residues). Since the only nearest neighbor to MeAde appears to be cytosine, we suggest that the methylated sequence is 5'... C-A(*)-C... 3' and that this methylation is mediated by the EcoK modification enzyme."} {"id": "PMID:159364", "title": "Electrophoretic characterization of intracellular forms of bacteriophage phi X174 DNA: identification of novel intermediate of altered superhelix density.", "content": "The replication cycle of bacteriophage phi X174 DNA has been analyzed by agarose gel electrophoresis. The electrophoretic behavior of the predominant species of parental and progeny DNA molecules formed between 5 and40 min after infection was deduced and quantitated. Migration through 1.4% agarose at 5 and 10 V/cm resolved all known viral DNA species as well as fragments of host chromosomal DNA. Among parental replicative form(RF) molecules synthesized, 1 to 3% were full length linear duplexes (RFIII) and approximately 65% were closed circular duplexes (RFI). Most of the input viral strands remained in a duplex structure throughout the period of infection studied here. Among progeny molecules, RFIII was not readily detected unless viral DNA synthesis was inhibited by chloramphenicol. Late in infection, 20% of the progeny RF were found to exist as form I dna. in addition, approximately 1% of the viral DNA was found as unit length linear single strands. Electrophoretic analysis of RF DNA after controlled denaturation suggests the existence of four populations of closed circular RF: (i) molecules of native superhelix density (RFI); (ii) a population of molecules of altered topological linking number, alpha, differing in increments of one superhelical turn (tau) between tau values of 0 and approximately -31; (iii) a superimposed population of topological isomers which under electrophoresis conditions have mean tau value (tau) equal to +5; and (iv) a population of \"complexed\" molecules with a reduced number of superhelical turns due to their association with single-stranded DNA and RNA. Complexed parental molecules isolated from cells infected at high multiplicity released FRI and homologous single-stranded DNA upon denaturation and are postulated to be intermediates in genetic recombination. Complexed RF DNA isolated from cells infected at low multiplicity release native supercoils upon reaction with RNase H and are observed by electron microscopy to contain displacement loops. Such molecules are likely intermediates in transcription. Our results are consistent with a structure of complexed RFI involving a partially triple-stranded helix in which a covalently closed circular duplex molecule contains a reduced number of superhelical turns due to the unwinding produced by base pairing between one strand of the supercoil and an associated homologous single strand of DNA or RNA.", "contents": "Electrophoretic characterization of intracellular forms of bacteriophage phi X174 DNA: identification of novel intermediate of altered superhelix density. The replication cycle of bacteriophage phi X174 DNA has been analyzed by agarose gel electrophoresis. The electrophoretic behavior of the predominant species of parental and progeny DNA molecules formed between 5 and40 min after infection was deduced and quantitated. Migration through 1.4% agarose at 5 and 10 V/cm resolved all known viral DNA species as well as fragments of host chromosomal DNA. Among parental replicative form(RF) molecules synthesized, 1 to 3% were full length linear duplexes (RFIII) and approximately 65% were closed circular duplexes (RFI). Most of the input viral strands remained in a duplex structure throughout the period of infection studied here. Among progeny molecules, RFIII was not readily detected unless viral DNA synthesis was inhibited by chloramphenicol. Late in infection, 20% of the progeny RF were found to exist as form I dna. in addition, approximately 1% of the viral DNA was found as unit length linear single strands. Electrophoretic analysis of RF DNA after controlled denaturation suggests the existence of four populations of closed circular RF: (i) molecules of native superhelix density (RFI); (ii) a population of molecules of altered topological linking number, alpha, differing in increments of one superhelical turn (tau) between tau values of 0 and approximately -31; (iii) a superimposed population of topological isomers which under electrophoresis conditions have mean tau value (tau) equal to +5; and (iv) a population of \"complexed\" molecules with a reduced number of superhelical turns due to their association with single-stranded DNA and RNA. Complexed parental molecules isolated from cells infected at high multiplicity released FRI and homologous single-stranded DNA upon denaturation and are postulated to be intermediates in genetic recombination. Complexed RF DNA isolated from cells infected at low multiplicity release native supercoils upon reaction with RNase H and are observed by electron microscopy to contain displacement loops. Such molecules are likely intermediates in transcription. Our results are consistent with a structure of complexed RFI involving a partially triple-stranded helix in which a covalently closed circular duplex molecule contains a reduced number of superhelical turns due to the unwinding produced by base pairing between one strand of the supercoil and an associated homologous single strand of DNA or RNA."} {"id": "PMID:159365", "title": "Sacral signal tracing: the electrophysiology of the bulbocavernosus reflex.", "content": "We studied 52 men with electrophysiologic testing of the bulbocavernosus reflex to determine reflex latency. The bulbocavernosus reflex was demonstrated to be a segmental polysynaptic reflex with cross-over in the sacral spinal cord. Excellent correlation was obtained between prolonged latency and clinical evidence of neuropathy. The examination may be useful clinically to evaluate patients suspected to have sacral cord lesions or pudendal neuropathy (for example impotence, chronic back pain and lesions of the cauda equina and peripheral nerves).", "contents": "Sacral signal tracing: the electrophysiology of the bulbocavernosus reflex. We studied 52 men with electrophysiologic testing of the bulbocavernosus reflex to determine reflex latency. The bulbocavernosus reflex was demonstrated to be a segmental polysynaptic reflex with cross-over in the sacral spinal cord. Excellent correlation was obtained between prolonged latency and clinical evidence of neuropathy. The examination may be useful clinically to evaluate patients suspected to have sacral cord lesions or pudendal neuropathy (for example impotence, chronic back pain and lesions of the cauda equina and peripheral nerves)."} {"id": "PMID:159366", "title": "The flow rate nomogram: I. Development.", "content": "In normal individuals the flow rate depends on the initial bladder volume in a non-linear fashion. A flow rate nomogram taking this relationship into account was developed as an aid in the interpretation of urinary flow rate data. With this approach excellent differentiation of normal from obstructed individuals was achieved. In addition, the variability in a single individual's flow rate over time was estimated to be relatively small and, thus, uroflowmetry may be used to identify changes in outflow resistance after medical or surgical therapy.", "contents": "The flow rate nomogram: I. Development. In normal individuals the flow rate depends on the initial bladder volume in a non-linear fashion. A flow rate nomogram taking this relationship into account was developed as an aid in the interpretation of urinary flow rate data. With this approach excellent differentiation of normal from obstructed individuals was achieved. In addition, the variability in a single individual's flow rate over time was estimated to be relatively small and, thus, uroflowmetry may be used to identify changes in outflow resistance after medical or surgical therapy."} {"id": "PMID:159367", "title": "Angiocardiograms and hemodynamics in idiopathic cardiomyopathy, with reference to histology of biopsied ventricular myocardium.", "content": "Cardiac catheterization, angiocardiography and ventricular muscle biopsy were performed in forty patients with idiopathic cardiomyopathy and included 21 cases of hypertrophic cardiomyopathy and 19 cases of congestive cardiomyopathy. 1) Cardiac catheterization revealed normal cardiac index and stroke index in both types, although there was a slight tendency toward decrease in cases of CCM. HCM showed slightly elevated right ventricular end-diastolic pressure and left ventricular end-diastolic pressure with a high incidence of atrial kick. CCM showed an elevated mean pulmonary artery, mean pulmonary wedge and left ventricular end-diastolic pressure. 2) Angiocardiographic findings revealed that in HCM left ventricular end-diastolic volume as well as left ventricular end-systolic volume, ejection fraction, meanVcf and MNSER were within normal range, and left ventricular anterior wall thickness, left ventricular mass and shortening of short axis in systole were increased. In CCM left ventricular end-diastolic volume and end-systolic volume increased, and ejection fraction, meanVcf, MNSER were decreased. The left ventricular anterior wall thickness was normal, and the left ventricular mass was smaller compared to the volume. The shortening of long and short axes in systole was slight. Left ventricular asynergy and mitral regurgitation occurred frequently. Coronary cineangiograms revealed normal patterns in both types. 3) Histological findings revealed hypertrophy of myofibers, degenerative changes, i.e. scarcity of myofibrils, deformity of nucleus and vacuolization of myocardial fibers, and collagen proliferation in both types. 4) No definite relationship was seen between parameters of left ventricular function and the findings of biopsied left ventricular muscle except for increase in wall thickness which might be apparently due to hypertrophy of the myocardial fibers.", "contents": "Angiocardiograms and hemodynamics in idiopathic cardiomyopathy, with reference to histology of biopsied ventricular myocardium. Cardiac catheterization, angiocardiography and ventricular muscle biopsy were performed in forty patients with idiopathic cardiomyopathy and included 21 cases of hypertrophic cardiomyopathy and 19 cases of congestive cardiomyopathy. 1) Cardiac catheterization revealed normal cardiac index and stroke index in both types, although there was a slight tendency toward decrease in cases of CCM. HCM showed slightly elevated right ventricular end-diastolic pressure and left ventricular end-diastolic pressure with a high incidence of atrial kick. CCM showed an elevated mean pulmonary artery, mean pulmonary wedge and left ventricular end-diastolic pressure. 2) Angiocardiographic findings revealed that in HCM left ventricular end-diastolic volume as well as left ventricular end-systolic volume, ejection fraction, meanVcf and MNSER were within normal range, and left ventricular anterior wall thickness, left ventricular mass and shortening of short axis in systole were increased. In CCM left ventricular end-diastolic volume and end-systolic volume increased, and ejection fraction, meanVcf, MNSER were decreased. The left ventricular anterior wall thickness was normal, and the left ventricular mass was smaller compared to the volume. The shortening of long and short axes in systole was slight. Left ventricular asynergy and mitral regurgitation occurred frequently. Coronary cineangiograms revealed normal patterns in both types. 3) Histological findings revealed hypertrophy of myofibers, degenerative changes, i.e. scarcity of myofibrils, deformity of nucleus and vacuolization of myocardial fibers, and collagen proliferation in both types. 4) No definite relationship was seen between parameters of left ventricular function and the findings of biopsied left ventricular muscle except for increase in wall thickness which might be apparently due to hypertrophy of the myocardial fibers."} {"id": "PMID:159376", "title": "Immunologic abnormalities in melanoma-prone families.", "content": "Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified.", "contents": "Immunologic abnormalities in melanoma-prone families. Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified."} {"id": "PMID:159383", "title": "Deposition of immune complexes in the ovarian follicle of rabbits with experimental chronic serum sickness. I. Immunopathology.", "content": "In the present study, deposition of antigen-antibody complexes in the ovarian follicles of the rabbit is described. Forty-one rabbits were immunized with multiple daily injections of bovine serum albumin. Twenty-two rabbits developed systemic chronic serum sickness. The ovaries of rabbits with systemic chronic serum sickness, those of the immunized rabbits that did not develop systemic chronic serum sickness, and those of the nonimmunized rabbits were studied by light, electron, and immunofluorescence microscopy. It was found that granular deposits of bovine serum albumin, rabbit IgG, and C3, presumably as antigen-antibody complexes, were frequently present in the zona pellucida of secondary and tertiary follicles, and in the corpora atretica of rabbits with systemic chronic serum sickness. The oocytes showed an increased number of vacuoles and phagosomes containing electron-opaque material. These observations may contribute to the study of immunologic mechanisms in the pathophysiology of the female reproductive system.", "contents": "Deposition of immune complexes in the ovarian follicle of rabbits with experimental chronic serum sickness. I. Immunopathology. In the present study, deposition of antigen-antibody complexes in the ovarian follicles of the rabbit is described. Forty-one rabbits were immunized with multiple daily injections of bovine serum albumin. Twenty-two rabbits developed systemic chronic serum sickness. The ovaries of rabbits with systemic chronic serum sickness, those of the immunized rabbits that did not develop systemic chronic serum sickness, and those of the nonimmunized rabbits were studied by light, electron, and immunofluorescence microscopy. It was found that granular deposits of bovine serum albumin, rabbit IgG, and C3, presumably as antigen-antibody complexes, were frequently present in the zona pellucida of secondary and tertiary follicles, and in the corpora atretica of rabbits with systemic chronic serum sickness. The oocytes showed an increased number of vacuoles and phagosomes containing electron-opaque material. These observations may contribute to the study of immunologic mechanisms in the pathophysiology of the female reproductive system."} {"id": "PMID:159384", "title": "Relational meaning encoded in the two-word utterances of stage 1 Down's syndrome children.", "content": "This study explored the early two-word utterances from four Down's syndrome children to determine if they encode the same relational meanings as children developing language normally. Nine semantic categories were established to classify the subject's two-word constructions. Absolute and proportional frequencies of relational types were then used to analyze the relational meanings. The results reveal that this classification system accounts for a combined 79% of the two-word utterances expressed by these Down's subjects. It is suggested that Down's children demonstrate as much diversity in their use of relational meanings as normals at the same linguistic stage. These findings are discussed with respect to what Down's children know about the world as they begin to produce two-word combinations.", "contents": "Relational meaning encoded in the two-word utterances of stage 1 Down's syndrome children. This study explored the early two-word utterances from four Down's syndrome children to determine if they encode the same relational meanings as children developing language normally. Nine semantic categories were established to classify the subject's two-word constructions. Absolute and proportional frequencies of relational types were then used to analyze the relational meanings. The results reveal that this classification system accounts for a combined 79% of the two-word utterances expressed by these Down's subjects. It is suggested that Down's children demonstrate as much diversity in their use of relational meanings as normals at the same linguistic stage. These findings are discussed with respect to what Down's children know about the world as they begin to produce two-word combinations."} {"id": "PMID:159385", "title": "Experience with the extracardiac conduit.", "content": "A review is made of all Mayo Clinic cases wherein 468 patients have received 516 extracardiac conduits in the repair of congenital heart defects. All patients had complex defects, which are classified in 10 basic diagnostic categories. The early mortality rate (which ranged from 4% to 49%, according to diagnostic group) averaged 25%, improving with experience. The postoperative complication rate was 70%. In 1% of operations, compression of the conduit was encountered at chest closure. The conduits placed in 333 patients contained a porcine valve. The conduit diameter averaged 22 mm. At completion of the operation, the mean gradient across the conduit was 22.8 mm Hg. At late study this mean gradient remained at 26 mm Hg in patients who had received the currently employed porcine-valved conduit. The average ratio of intraoperative postrepair ventricular (RV/LV) systolic pressures was 0.68. It was lower among the group who were to survive but was not ov prognostic value in individual cases. Among patients who survived the postoperative period, the late mortality rate (based on a mean of 3.6 years' follow-up) averaged 3.5% per year. Of the long-term survivors, 18% have required reoperation, primarily for replacement of calcified aortic homograft conduits used in the earlier part of the experience. Only 0.8% of porcine-valved conduits have required reoperation. Unrestricted life-styles were possible for 90% of survivors.", "contents": "Experience with the extracardiac conduit. A review is made of all Mayo Clinic cases wherein 468 patients have received 516 extracardiac conduits in the repair of congenital heart defects. All patients had complex defects, which are classified in 10 basic diagnostic categories. The early mortality rate (which ranged from 4% to 49%, according to diagnostic group) averaged 25%, improving with experience. The postoperative complication rate was 70%. In 1% of operations, compression of the conduit was encountered at chest closure. The conduits placed in 333 patients contained a porcine valve. The conduit diameter averaged 22 mm. At completion of the operation, the mean gradient across the conduit was 22.8 mm Hg. At late study this mean gradient remained at 26 mm Hg in patients who had received the currently employed porcine-valved conduit. The average ratio of intraoperative postrepair ventricular (RV/LV) systolic pressures was 0.68. It was lower among the group who were to survive but was not ov prognostic value in individual cases. Among patients who survived the postoperative period, the late mortality rate (based on a mean of 3.6 years' follow-up) averaged 3.5% per year. Of the long-term survivors, 18% have required reoperation, primarily for replacement of calcified aortic homograft conduits used in the earlier part of the experience. Only 0.8% of porcine-valved conduits have required reoperation. Unrestricted life-styles were possible for 90% of survivors."} {"id": "PMID:159395", "title": "Changes in membrane structure and function during chick embryonic erythropoiesis.", "content": "We found considerable differences in the pattern of membrane proteins as well as in the relative amounts of individual components in isolated chick red blood cell membranes during the course of embryonic development. Of special interest in the increase in the relative amounts of two major polypeptides, band 3 and 3.1 (MW 100,000 daltons) with increasing age of the cells. With respect to functional studies, we found that the magnitude of sulfate influx decreases with increasing age of the embryo. Furthermore, the activity of ouabain-sensitive ATPase increases with increasing age (2.5-day embryo to adult). In addition, both the basal and the fluoride-stimulated adenylate cyclase activities decrease as the embryo age increases, whereas the enzyme sensitivity to epinephrine increases with increasing age of the embryo.", "contents": "Changes in membrane structure and function during chick embryonic erythropoiesis. We found considerable differences in the pattern of membrane proteins as well as in the relative amounts of individual components in isolated chick red blood cell membranes during the course of embryonic development. Of special interest in the increase in the relative amounts of two major polypeptides, band 3 and 3.1 (MW 100,000 daltons) with increasing age of the cells. With respect to functional studies, we found that the magnitude of sulfate influx decreases with increasing age of the embryo. Furthermore, the activity of ouabain-sensitive ATPase increases with increasing age (2.5-day embryo to adult). In addition, both the basal and the fluoride-stimulated adenylate cyclase activities decrease as the embryo age increases, whereas the enzyme sensitivity to epinephrine increases with increasing age of the embryo."} {"id": "PMID:159397", "title": "Delayed-type hypersensitivity (DTH) in BCG-sensitized mice I. Lack of suppressor T cell activity on DTH to sheep red blood cells.", "content": "Mice pretreated with an intravenous (i.v.) injection of BCG (BCG-sensitized mice) and then immunized intravenously with a high dose (10(8)--10(9)) of sheep red blood cells (SRBC) 2 weeks later developed strong delayed-type hypersensitivity (DTH) to SRBC, as in mice pretreated with cyclophosphamide (CY) (CY-treated mice) and then immunized with SRBC 2 days later; normal mice given the same dose of SRBC did not show such DTH. The mechanism of this strong DTH to SRBC which developed in BCG-sensitized mice was studied, by comparing it with that in CY-treated mice. The transfer of either whole spleen cells or thymus cells, but not serum, obtained from mice immunized with i.v. injections of 10(9) SRBC 4 days previously (hyperimmune mice) did not suppress either the induction or the expression of DTH to SRBC in BCG-sensitized mice, but suppressed those in CY-treated mice. The suppressor cells were SRBC-specific T cells. Adoptive transfer of DTH to SRBC by spleen cells from either BCG-sensitized mice of CY-treated mice to hyperimmune recipients failed. The adoptive transfer of DTH from BCG-sensitized mice to normal recipients also failed if the spleen cells from hyperimmune mice were cotransferred. Whole body irradiation (600 rad) of mice 2 hr before or after the time of immunization with SRBC reduced significantly DTH to SRBC in both BCG-sensitized and CY-treated mice. It was noticed that the total number of spleen cells in BCG-sensitized mice was 3--4 times larger than that in CY-treated mice. From these results, we conclude that the entity of effector T cells of DTH to SRBC induced in BCG-sensitized mice and in CY-treated mice was not different in terms of susceptibility to suppressor T cells and irradiation, but that the total numbers of effector T cells generated in these mice differed remarkably, resulting in the above-described different responsiveness to suppressor T cells transferred passively.", "contents": "Delayed-type hypersensitivity (DTH) in BCG-sensitized mice I. Lack of suppressor T cell activity on DTH to sheep red blood cells. Mice pretreated with an intravenous (i.v.) injection of BCG (BCG-sensitized mice) and then immunized intravenously with a high dose (10(8)--10(9)) of sheep red blood cells (SRBC) 2 weeks later developed strong delayed-type hypersensitivity (DTH) to SRBC, as in mice pretreated with cyclophosphamide (CY) (CY-treated mice) and then immunized with SRBC 2 days later; normal mice given the same dose of SRBC did not show such DTH. The mechanism of this strong DTH to SRBC which developed in BCG-sensitized mice was studied, by comparing it with that in CY-treated mice. The transfer of either whole spleen cells or thymus cells, but not serum, obtained from mice immunized with i.v. injections of 10(9) SRBC 4 days previously (hyperimmune mice) did not suppress either the induction or the expression of DTH to SRBC in BCG-sensitized mice, but suppressed those in CY-treated mice. The suppressor cells were SRBC-specific T cells. Adoptive transfer of DTH to SRBC by spleen cells from either BCG-sensitized mice of CY-treated mice to hyperimmune recipients failed. The adoptive transfer of DTH from BCG-sensitized mice to normal recipients also failed if the spleen cells from hyperimmune mice were cotransferred. Whole body irradiation (600 rad) of mice 2 hr before or after the time of immunization with SRBC reduced significantly DTH to SRBC in both BCG-sensitized and CY-treated mice. It was noticed that the total number of spleen cells in BCG-sensitized mice was 3--4 times larger than that in CY-treated mice. From these results, we conclude that the entity of effector T cells of DTH to SRBC induced in BCG-sensitized mice and in CY-treated mice was not different in terms of susceptibility to suppressor T cells and irradiation, but that the total numbers of effector T cells generated in these mice differed remarkably, resulting in the above-described different responsiveness to suppressor T cells transferred passively."} {"id": "PMID:159399", "title": "Down's syndrome, hypothyroidism and diabetes mellitus in an adult.", "content": "Primary hypothyroidism was diagnosed in a woman aged 33 years, with Down's syndrome and insulin-dependent diabetes mellitus after admission to hospital with hypoglycaemia. The diabetes was stabilized and treatment was commenced with L-thyroxine with a good clinical response. The patient's mother and older sister also had hypothyroidism and all three had no thyroid antibodies. The importance of diagnosing and treating primary hypothyroidism in adult patients with Down's syndrome is stressed even in the absence of thyroid antibodies.", "contents": "Down's syndrome, hypothyroidism and diabetes mellitus in an adult. Primary hypothyroidism was diagnosed in a woman aged 33 years, with Down's syndrome and insulin-dependent diabetes mellitus after admission to hospital with hypoglycaemia. The diabetes was stabilized and treatment was commenced with L-thyroxine with a good clinical response. The patient's mother and older sister also had hypothyroidism and all three had no thyroid antibodies. The importance of diagnosing and treating primary hypothyroidism in adult patients with Down's syndrome is stressed even in the absence of thyroid antibodies."} {"id": "PMID:159398", "title": "[Electron microscopic study of the pond microflora of the Amu-Dar'ia River delta].", "content": "Bacterial forms were studied by electron microscopy in weakly saline lakes of the mesotrophic type in the Amu Darya delta; these forms differed in the character of water nutrition, certain physico-chemical and biological properties. The main population in the lakes represented by Vibrio and rods among which many small forms (0.3--0.5 mu) were found. Long filamentous forms were often encountered. A considerable number of organisms possessed prosthecae, fimbria and various protrustions. Budding bacteria were also detected. Microorganisms with peculiar morphology were most abundant in such places where the total incidence of bacteria was 1x10(6) per litre while water transparency was low.", "contents": "[Electron microscopic study of the pond microflora of the Amu-Dar'ia River delta]. Bacterial forms were studied by electron microscopy in weakly saline lakes of the mesotrophic type in the Amu Darya delta; these forms differed in the character of water nutrition, certain physico-chemical and biological properties. The main population in the lakes represented by Vibrio and rods among which many small forms (0.3--0.5 mu) were found. Long filamentous forms were often encountered. A considerable number of organisms possessed prosthecae, fimbria and various protrustions. Budding bacteria were also detected. Microorganisms with peculiar morphology were most abundant in such places where the total incidence of bacteria was 1x10(6) per litre while water transparency was low."} {"id": "PMID:159402", "title": "[Comparative morphological studies of the structure of the articular disk of the temporomandibular joint].", "content": "Articular disks (DA) of mandibular articulations of several types of animals of different ages and both sexes (herbivora, carnivora, rodents and omnivora) were studied. Comparative macroscopy emphasized similarities with the DA of humans and other omnivora, as well as some peculiarities. DA is ellyptical in herbivora; its upper surface is divided into two facets by a transversal crest. DA is pinkish and square in carnivora; its posterior part is lacking. DA is half-moonish and white-nacreous in rodents; its upper surface presents a longitudinal crest. Microscopy evidenced some differences: the collagen fibrils are dominating in herbivora, while in carnivora the elastic ones. The rodents present rare elastic fibers; these animals and the ruminants show capillaries in the central part of the DA, while in other animals these are absent. Cells are mainly located in the upper superficial layers of DA. Relationships between form, histological structure and functions, mainly regarding the mastication types, are discussed.", "contents": "[Comparative morphological studies of the structure of the articular disk of the temporomandibular joint]. Articular disks (DA) of mandibular articulations of several types of animals of different ages and both sexes (herbivora, carnivora, rodents and omnivora) were studied. Comparative macroscopy emphasized similarities with the DA of humans and other omnivora, as well as some peculiarities. DA is ellyptical in herbivora; its upper surface is divided into two facets by a transversal crest. DA is pinkish and square in carnivora; its posterior part is lacking. DA is half-moonish and white-nacreous in rodents; its upper surface presents a longitudinal crest. Microscopy evidenced some differences: the collagen fibrils are dominating in herbivora, while in carnivora the elastic ones. The rodents present rare elastic fibers; these animals and the ruminants show capillaries in the central part of the DA, while in other animals these are absent. Cells are mainly located in the upper superficial layers of DA. Relationships between form, histological structure and functions, mainly regarding the mastication types, are discussed."} {"id": "PMID:159404", "title": "[The ultrastructure of embryonic capillaries in the neuroepithelium of the brain vesicles].", "content": "The electronmicroscopic control of the capillaries of the brain vesicles in 5--6-day-old chick embryos revealed an intimate contact between capillary walls and neuroblasts, and on the other hand the presence of a functional endoplasmic reticulum in the endothelial cells. These are only very few vacuoles for protein transport in the cytoplasm of endothelial cells.", "contents": "[The ultrastructure of embryonic capillaries in the neuroepithelium of the brain vesicles]. The electronmicroscopic control of the capillaries of the brain vesicles in 5--6-day-old chick embryos revealed an intimate contact between capillary walls and neuroblasts, and on the other hand the presence of a functional endoplasmic reticulum in the endothelial cells. These are only very few vacuoles for protein transport in the cytoplasm of endothelial cells."} {"id": "PMID:159415", "title": "Late Eocene of Burma yields earliest anthropoid primate, Pondaungia cotteri.", "content": "In April 1978, a fragment of a primate lower jaw containing the second and third molar teeth was found in late Eocene exposures of the Pondaung Hills about 1 mile north-west of Mogaung village in northwestern Central Burma. This approximately 40-Myr-old specimen is the first fossil primate found in Burma since the fragmentary remains of the controversial earliest anthropoids Pondaungia cotteri Pilgrim and Amphipithecus mogaungensis Colbert were recovered more than 50 yr ago. The jaw described here is believed to represent further evidence of P. cotteri. Its recovery from undoubled late Eocene exposures coupled with its salient higher primate characters and excellent state of preservation provides the opportunity to substantiate further that the Pondaung primates of Burma are the earliest known record of the Anthropoidea.", "contents": "Late Eocene of Burma yields earliest anthropoid primate, Pondaungia cotteri. In April 1978, a fragment of a primate lower jaw containing the second and third molar teeth was found in late Eocene exposures of the Pondaung Hills about 1 mile north-west of Mogaung village in northwestern Central Burma. This approximately 40-Myr-old specimen is the first fossil primate found in Burma since the fragmentary remains of the controversial earliest anthropoids Pondaungia cotteri Pilgrim and Amphipithecus mogaungensis Colbert were recovered more than 50 yr ago. The jaw described here is believed to represent further evidence of P. cotteri. Its recovery from undoubled late Eocene exposures coupled with its salient higher primate characters and excellent state of preservation provides the opportunity to substantiate further that the Pondaung primates of Burma are the earliest known record of the Anthropoidea."} {"id": "PMID:159418", "title": "Knowledge and technology needed for further development of mental health programmes.", "content": "Different preventive approaches of mental and neurological disorders are discussed. Special emphasis has been put on the advances of biological research in the elucidation of aetiological and pathogenic mechanisms of major psychoses, such as schizophrenia and affective disorders. Perspectives of genetic and psychopharmacological research are emphasized. Multidisciplinary efforts are needed for the improvement of existing preventive measures.", "contents": "Knowledge and technology needed for further development of mental health programmes. Different preventive approaches of mental and neurological disorders are discussed. Special emphasis has been put on the advances of biological research in the elucidation of aetiological and pathogenic mechanisms of major psychoses, such as schizophrenia and affective disorders. Perspectives of genetic and psychopharmacological research are emphasized. Multidisciplinary efforts are needed for the improvement of existing preventive measures."} {"id": "PMID:159419", "title": "Familial inverted choreoathetosis.", "content": "We present a family with infantile onset of progressive choreoathetosis. The movements affected the legs predominantly and also impaired gait. No dementia, seizures, or rigidity was noted. Inheritance was autosomal dominant. This new familial movement disorder can be differentiated easily from other hereditary choreas.", "contents": "Familial inverted choreoathetosis. We present a family with infantile onset of progressive choreoathetosis. The movements affected the legs predominantly and also impaired gait. No dementia, seizures, or rigidity was noted. Inheritance was autosomal dominant. This new familial movement disorder can be differentiated easily from other hereditary choreas."} {"id": "PMID:159414", "title": "Morphology and physiology of skeletal muscle in aging rodents.", "content": "Aging in the rodent is accompanied by a progressive loss of skeletal muscle fibers. The muscle twitch also becomes slower, probably as a result of fiber-type conversion from \"fast-twitch\" to \"slow-twitch.\" The loss of muscle fibers precedes signs of obvious weakness and appears to involve the loss of entire functioning motor units. In the mouse, this loss of motor units correlated with a loss of axons from the innervating nerve trunks.", "contents": "Morphology and physiology of skeletal muscle in aging rodents. Aging in the rodent is accompanied by a progressive loss of skeletal muscle fibers. The muscle twitch also becomes slower, probably as a result of fiber-type conversion from \"fast-twitch\" to \"slow-twitch.\" The loss of muscle fibers precedes signs of obvious weakness and appears to involve the loss of entire functioning motor units. In the mouse, this loss of motor units correlated with a loss of axons from the innervating nerve trunks."} {"id": "PMID:159421", "title": "[Closed abdominal injuries in patients with multiple injuries. Diagnostic considerations on 74 cases].", "content": "A diagnostic assessment was made of 74 cases of non-penetrating abdominal wounds observed over the previous 5 years. Laparoscopy performed in 49 polytraumatised patients made a decisive contribution to accurate, early diagnosis, with an indication for emergency surgery in 35 cases (32 visceral lesions and 3 retroperitoneal haematoma), whereas it was clear from the negative finding that surgery was not required in the remaining 14. It is felt that all additional radiological and instrumental diagnostic should be employed, and that careful clinical examination and repeated inspection, preferably by the same surgeon, are important in cases of multiple injury, since the situation may become dramatically worse in the space of a few hours.", "contents": "[Closed abdominal injuries in patients with multiple injuries. Diagnostic considerations on 74 cases]. A diagnostic assessment was made of 74 cases of non-penetrating abdominal wounds observed over the previous 5 years. Laparoscopy performed in 49 polytraumatised patients made a decisive contribution to accurate, early diagnosis, with an indication for emergency surgery in 35 cases (32 visceral lesions and 3 retroperitoneal haematoma), whereas it was clear from the negative finding that surgery was not required in the remaining 14. It is felt that all additional radiological and instrumental diagnostic should be employed, and that careful clinical examination and repeated inspection, preferably by the same surgeon, are important in cases of multiple injury, since the situation may become dramatically worse in the space of a few hours."} {"id": "PMID:159425", "title": "Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients.", "content": "To test the possibility of endorphin release in clinical pain states naloxone was given, alternate with saline, in a double-blind study to 10 patients with chronic neuralgia or low back pain. There was no significant alteration of the levels of spontaneous pain or heat pain thresholds. The results suggest that the endorphin system does not offer protection of any importance in chronic pain.", "contents": "Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients. To test the possibility of endorphin release in clinical pain states naloxone was given, alternate with saline, in a double-blind study to 10 patients with chronic neuralgia or low back pain. There was no significant alteration of the levels of spontaneous pain or heat pain thresholds. The results suggest that the endorphin system does not offer protection of any importance in chronic pain."} {"id": "PMID:159426", "title": "Bone marrow transplantation (1958-1978) : conditioning and graft-versus-host disease, indications in aplasias and leukemias.", "content": "Bone marrow transplantation (BMT), which stimulated great hope for treatment of aplasias and leukemias in 1958 following our first success in grafting this tissue, is, after a long period of study and development, experiencing renewed interest since it is now possible to obtain, in case of transplantation with genotypically matched sibling donors, 70% long survival (cures ?) in aplasia (under the condition that the recipient is not sensitized by previous transfusions) and in leukemia (under the condition that the recipient is transplanted in a period of remission and is not sensitized by transfusions). When the patient does not possess any genotypically matched donor, a trial of incompatible bone marrow transplantation after conditioning with antilymphocyte serum is reasonable, since we have obtained good, although unexplained, results with this method, which should be pursued. In any case, these transplants must be done in intensive care units in hemato-oncology departments.", "contents": "Bone marrow transplantation (1958-1978) : conditioning and graft-versus-host disease, indications in aplasias and leukemias. Bone marrow transplantation (BMT), which stimulated great hope for treatment of aplasias and leukemias in 1958 following our first success in grafting this tissue, is, after a long period of study and development, experiencing renewed interest since it is now possible to obtain, in case of transplantation with genotypically matched sibling donors, 70% long survival (cures ?) in aplasia (under the condition that the recipient is not sensitized by previous transfusions) and in leukemia (under the condition that the recipient is transplanted in a period of remission and is not sensitized by transfusions). When the patient does not possess any genotypically matched donor, a trial of incompatible bone marrow transplantation after conditioning with antilymphocyte serum is reasonable, since we have obtained good, although unexplained, results with this method, which should be pursued. In any case, these transplants must be done in intensive care units in hemato-oncology departments."} {"id": "PMID:159431", "title": "Cellular (T cell) immunity in the human newborn.", "content": "The cellular immune system of the human newborn, like the rest of the immunologic apparatus, is anatomically intact, antigenically inexperienced, and functionally deficient. The latter is suggested by the newborns' enhanced susceptibility to infection, diminished delayed cutaneous hypersensitivity reactions, and selective abnormalities (when compared to adults) of measures of cellular immunity in vitro. These include impaired proliferative response to ubiquitous antigens, depressed lymphotoxin, migration inhibition factor, and immune interferon production, and diminished cytotoxic reactions including cell-mediated lympholysis. By contrast, other aspects of neonatal T cell function, such as to mitogens or allogeneic lymphocytes, natural interferon and leukocyte inhibition factor production, and number and percentage of E-rosette-forming cell are generally normal. These decreased functional properties may provide an explanation for the newborns' susceptibility to infection and for the occasional occurrence of engraftment of foreign cells from either the mother or from prenatal or neonatal blood transfusion.", "contents": "Cellular (T cell) immunity in the human newborn. The cellular immune system of the human newborn, like the rest of the immunologic apparatus, is anatomically intact, antigenically inexperienced, and functionally deficient. The latter is suggested by the newborns' enhanced susceptibility to infection, diminished delayed cutaneous hypersensitivity reactions, and selective abnormalities (when compared to adults) of measures of cellular immunity in vitro. These include impaired proliferative response to ubiquitous antigens, depressed lymphotoxin, migration inhibition factor, and immune interferon production, and diminished cytotoxic reactions including cell-mediated lympholysis. By contrast, other aspects of neonatal T cell function, such as to mitogens or allogeneic lymphocytes, natural interferon and leukocyte inhibition factor production, and number and percentage of E-rosette-forming cell are generally normal. These decreased functional properties may provide an explanation for the newborns' susceptibility to infection and for the occasional occurrence of engraftment of foreign cells from either the mother or from prenatal or neonatal blood transfusion."} {"id": "PMID:159449", "title": "Isolation and identification of bacteriophage phi X174 prohead.", "content": "The morphogenesis of bacteriophage phi X174 has been investigated by using an in vitro DNA synthesizing system. An extract of a B-mutant-infected cell is capable of synthesizing infectious phage in vitro when the B gene function is provided by the addition of an ammonium sulfate fraction of a C-mutant-infected-cell extract. This fraction contains the omega complex, a complex of phage-coded proteins with S = 108; the B-mutant extract does not. The purified omega complex, isolated from the C-mutant extract, caused the synthesis and encapsidation of viral DNA when added to B-mutant extract. The omega complex contains the B protein but it is the intact omega complex that functioned in the in vitro complementation of the B-mutant extract because other fractions containing B protein but no omega complex had little or no complementing activity. The results indicate that the omega complex is the phi X174 prohead. The B protein is not found in either the 132S or 114S phage particles but is an essential component of the prohead. This suggests that it may have a scaffolding function.", "contents": "Isolation and identification of bacteriophage phi X174 prohead. The morphogenesis of bacteriophage phi X174 has been investigated by using an in vitro DNA synthesizing system. An extract of a B-mutant-infected cell is capable of synthesizing infectious phage in vitro when the B gene function is provided by the addition of an ammonium sulfate fraction of a C-mutant-infected-cell extract. This fraction contains the omega complex, a complex of phage-coded proteins with S = 108; the B-mutant extract does not. The purified omega complex, isolated from the C-mutant extract, caused the synthesis and encapsidation of viral DNA when added to B-mutant extract. The omega complex contains the B protein but it is the intact omega complex that functioned in the in vitro complementation of the B-mutant extract because other fractions containing B protein but no omega complex had little or no complementing activity. The results indicate that the omega complex is the phi X174 prohead. The B protein is not found in either the 132S or 114S phage particles but is an essential component of the prohead. This suggests that it may have a scaffolding function."} {"id": "PMID:159450", "title": "Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation.", "content": "DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with the active participation of a proofreading mechanism that hydrolytically excises mismatched base pairs as they are formed. A simple kinetic analysis predicts that the frequency of misincorporation depends on the ratio of incorrect to correct deoxynucleoside triphosphates times the concentration of the next triphosphate in the sequence to be added. This suggests that spontaneous mutation by misincorporation depends crucially on the composition of the deoxynucleoside triphosphate pool.", "contents": "Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation. DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with the active participation of a proofreading mechanism that hydrolytically excises mismatched base pairs as they are formed. A simple kinetic analysis predicts that the frequency of misincorporation depends on the ratio of incorrect to correct deoxynucleoside triphosphates times the concentration of the next triphosphate in the sequence to be added. This suggests that spontaneous mutation by misincorporation depends crucially on the composition of the deoxynucleoside triphosphate pool."} {"id": "PMID:159451", "title": "Active site trapping of nucleotides by crosslinking two sulfhydryls in myosin subfragment 1.", "content": "Studies with reagents that crosslink two thiol groups have shown that it is possible to trap nucleotides at the active site of myosin chymotryptic subfragment 1. Subfragment 1 incorporates nearly stoichiometric quantities of [14C]ATP or [14C]ADP in a manner that depends linearly on the extent of inactivation by either N,N'-p-phenylenedimaleimide or Co(II)phenanthroline/[Co(III)(phenanthroline)2CO3]+ complexes. The incorporated radioactive nucleotide is retained after gel filtration, even when the enzyme derivatives are stored in the presence of EDTA or nonradioactive nucleotides (t 1/2 approximately 5 days). The nucleotide incorporated is not covalently bound because HClO4 denaturation allows immediate release of bound nucleotide. The nucleotide retained is ADP because the gamma-phosphate of [gamma-32P]ATP is lost after trapping. Subfragment 1 inactivated as above does not bind the competitive inhibitor adenosine 5'-[beta, gamma-imido]triphosphate, indicating that the active site is blocked. It is proposed that a jawlike nucleotide cleft closes on MgADP or MgATP, which can be locked shut by crosslinking two thiol groups by reaction with N,N'-p-phenylenedimaleimide or cobalt phenanthroline complexes.", "contents": "Active site trapping of nucleotides by crosslinking two sulfhydryls in myosin subfragment 1. Studies with reagents that crosslink two thiol groups have shown that it is possible to trap nucleotides at the active site of myosin chymotryptic subfragment 1. Subfragment 1 incorporates nearly stoichiometric quantities of [14C]ATP or [14C]ADP in a manner that depends linearly on the extent of inactivation by either N,N'-p-phenylenedimaleimide or Co(II)phenanthroline/[Co(III)(phenanthroline)2CO3]+ complexes. The incorporated radioactive nucleotide is retained after gel filtration, even when the enzyme derivatives are stored in the presence of EDTA or nonradioactive nucleotides (t 1/2 approximately 5 days). The nucleotide incorporated is not covalently bound because HClO4 denaturation allows immediate release of bound nucleotide. The nucleotide retained is ADP because the gamma-phosphate of [gamma-32P]ATP is lost after trapping. Subfragment 1 inactivated as above does not bind the competitive inhibitor adenosine 5'-[beta, gamma-imido]triphosphate, indicating that the active site is blocked. It is proposed that a jawlike nucleotide cleft closes on MgADP or MgATP, which can be locked shut by crosslinking two thiol groups by reaction with N,N'-p-phenylenedimaleimide or cobalt phenanthroline complexes."} {"id": "PMID:159452", "title": "Interactions between DNA-bound repressors govern regulation by the lambda phage repressor.", "content": "The lambda phage repressor binds cooperatively to the three sites in the right operator (O(R)) according to the following pattern. If the DNA is wild type, O(R)1 and O(R)2 are filled coordinately because of interactions between repressor dimers bound to these two sites. Site O(R)3 is filled only at higher repressor concentrations. In contrast, if O(R)1 is mutant, O(R)2 and O(R)3 are filled coordinately because of interactions between repressors bound to these sites. In this case, the affinity of O(R)3 is increased and that of O(R)2 is decreased relative to the wild type. We infer that a repressor dimer bound to the middle site O(R)2 can interact either with another repressor dimer bound to O(R)1 (wild-type case) or, alternatively, with one bound to O(R)3 (mutant O(R)1 case). We argue that these repressor interactions are mediated by protein-protein contacts between adjacent repressor dimers, because the isolated amino-terminal domains of repressor bind to the operator sites noncooperatively. The cro protein of phage lambda, a second regulatory protein, which recognizes the same three sites in O(R) as does repressor, binds non-cooperatively. Experiments performed in vivo show that regulation of gene expression by repressor can be influenced critically by cooperative interactions. We demonstrate that the effect of repressor in a lysogen on the activity of the promoter P(RM) can be changed from activation to repression by deletion of O(R)1. We explain this effect in terms of the alternative cooperative interactions described above.", "contents": "Interactions between DNA-bound repressors govern regulation by the lambda phage repressor. The lambda phage repressor binds cooperatively to the three sites in the right operator (O(R)) according to the following pattern. If the DNA is wild type, O(R)1 and O(R)2 are filled coordinately because of interactions between repressor dimers bound to these two sites. Site O(R)3 is filled only at higher repressor concentrations. In contrast, if O(R)1 is mutant, O(R)2 and O(R)3 are filled coordinately because of interactions between repressors bound to these sites. In this case, the affinity of O(R)3 is increased and that of O(R)2 is decreased relative to the wild type. We infer that a repressor dimer bound to the middle site O(R)2 can interact either with another repressor dimer bound to O(R)1 (wild-type case) or, alternatively, with one bound to O(R)3 (mutant O(R)1 case). We argue that these repressor interactions are mediated by protein-protein contacts between adjacent repressor dimers, because the isolated amino-terminal domains of repressor bind to the operator sites noncooperatively. The cro protein of phage lambda, a second regulatory protein, which recognizes the same three sites in O(R) as does repressor, binds non-cooperatively. Experiments performed in vivo show that regulation of gene expression by repressor can be influenced critically by cooperative interactions. We demonstrate that the effect of repressor in a lysogen on the activity of the promoter P(RM) can be changed from activation to repression by deletion of O(R)1. We explain this effect in terms of the alternative cooperative interactions described above."} {"id": "PMID:159453", "title": "Homologous pairing in genetic recombination: complexes of recA protein and DNA.", "content": "recA protein, which is essential for general genetic recombination in Escherichia coli, promotes the homologous pairing of single-stranded DNA with double-stranded DNA to form a D loop. The amount of recA protein required for the reaction was directly proportional to the amount of single stranded DNA and was unaffected by similar variations in the amount of double-stranded DNA. The ATP analog, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), which was not rapidly hydrolyzed by recA protein, blocked the formation of D loops but promoted the formation of stable complexes of recA protein and single-stranded DNA. These complexes, in turn, bound homologous or heterologous double-stranded DNA and partially unwound it. Because ATP gamma S competitively inhibited the ATPase activity of recA protein (Km/Ki approximately 300), we infer that ATP gamma S binds at a site that overlaps the site for ATP and that the functional complexes formed in the presence of the analog probably represent partial steps in the overall reaction. If the complexes formed in the presence of ATP gamma S reflect natural intermediates in the formation of D loops, recA protein must promote homologous pairing either by moving juxtaposed single-stranded and double-stranded DNA relative to one another or by forming and dissociating complexes reiteratively until a homologous match occurs.", "contents": "Homologous pairing in genetic recombination: complexes of recA protein and DNA. recA protein, which is essential for general genetic recombination in Escherichia coli, promotes the homologous pairing of single-stranded DNA with double-stranded DNA to form a D loop. The amount of recA protein required for the reaction was directly proportional to the amount of single stranded DNA and was unaffected by similar variations in the amount of double-stranded DNA. The ATP analog, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), which was not rapidly hydrolyzed by recA protein, blocked the formation of D loops but promoted the formation of stable complexes of recA protein and single-stranded DNA. These complexes, in turn, bound homologous or heterologous double-stranded DNA and partially unwound it. Because ATP gamma S competitively inhibited the ATPase activity of recA protein (Km/Ki approximately 300), we infer that ATP gamma S binds at a site that overlaps the site for ATP and that the functional complexes formed in the presence of the analog probably represent partial steps in the overall reaction. If the complexes formed in the presence of ATP gamma S reflect natural intermediates in the formation of D loops, recA protein must promote homologous pairing either by moving juxtaposed single-stranded and double-stranded DNA relative to one another or by forming and dissociating complexes reiteratively until a homologous match occurs."} {"id": "PMID:159454", "title": "Efficient transformation of Neurospora crassa by utilizing hybrid plasmid DNA.", "content": "An efficient transformation system has been developed for Neurospora crassa that uses spheroplasts and pVK88 plasmid DNA. pVK88 is a recombinant Escherichia coli plasmid carrying the N. crassa qa-2(+) gene which encodes catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) and is part of the qa gene cluster. The recipient strain carries a stable qa-2(-) mutation and an arom-9(-) mutation, thus lacking both catabolic and biosynthetic dehydroquinase activities. Transformants were selected as colonies able to grow in the absence of an aromatic amino acid supplement. These colonies were qa-2(+) and had normal levels of catabolic dehydroquinase. DNA.DNA hybridization evidence with appropriate labeled probes indicates clearly that in some instances transformation involves the integration of bacterial plasmid sequences together with the qa-2(+) gene into the N. crassa genome. On the basis of genetic, enzyme assay, and DNA hybridization data, at least three types of transformation events can be distinguished: (i) replacement of the qa-2(-) gene by the qa-2(+) gene without any effect on the expression of the other genes in the qa cluster, (ii) linked insertion of a normal qa-2(+) gene accompanied by inactivation of the adjacent qa-4(+) gene, and (iii) insertion of a normal qa-2(+) gene at an unlinked site in the N. crassa genome. This newly integrated qa-2(+) genetic material is inherited in a typical Mendelian fashion. A low level of transformation has also been obtained by using linear total N. crassa DNA. Two such qa-2(+) transformants are unlinked to the qa-2(-) gene of the recipient.", "contents": "Efficient transformation of Neurospora crassa by utilizing hybrid plasmid DNA. An efficient transformation system has been developed for Neurospora crassa that uses spheroplasts and pVK88 plasmid DNA. pVK88 is a recombinant Escherichia coli plasmid carrying the N. crassa qa-2(+) gene which encodes catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) and is part of the qa gene cluster. The recipient strain carries a stable qa-2(-) mutation and an arom-9(-) mutation, thus lacking both catabolic and biosynthetic dehydroquinase activities. Transformants were selected as colonies able to grow in the absence of an aromatic amino acid supplement. These colonies were qa-2(+) and had normal levels of catabolic dehydroquinase. DNA.DNA hybridization evidence with appropriate labeled probes indicates clearly that in some instances transformation involves the integration of bacterial plasmid sequences together with the qa-2(+) gene into the N. crassa genome. On the basis of genetic, enzyme assay, and DNA hybridization data, at least three types of transformation events can be distinguished: (i) replacement of the qa-2(-) gene by the qa-2(+) gene without any effect on the expression of the other genes in the qa cluster, (ii) linked insertion of a normal qa-2(+) gene accompanied by inactivation of the adjacent qa-4(+) gene, and (iii) insertion of a normal qa-2(+) gene at an unlinked site in the N. crassa genome. This newly integrated qa-2(+) genetic material is inherited in a typical Mendelian fashion. A low level of transformation has also been obtained by using linear total N. crassa DNA. Two such qa-2(+) transformants are unlinked to the qa-2(-) gene of the recipient."} {"id": "PMID:159455", "title": "Cloning of the structural gene (ompA) for an integral outer membrane protein of Escherichia coli K-12.", "content": "The gene (ompA) for the major outer membrane protein II* from Escherichia coli K-12 has been cloned on a 5-megadalton EcoRI fragment by using phage lambda as vector. The gene is expressed during the lytic cycle of the recombinant phage and the insoluble membrane-bound protein was detected in phage plaques with a simple radioimmunoassay. Transfer of the EcoRI fragment into plasmid pSC101 and expression in a host lacking protein II* led to overproduction of protein II* and decreased production of two other major outer membrane proteins. Expression of the plasmid pSC101-ompA+ in minicells derived from an ompA minicell-producing strain led to synthesis, at high rates, of this protein and massive accumulation of a second cell envelope protein most likely representing the biosynthetic precursor of protein II*.", "contents": "Cloning of the structural gene (ompA) for an integral outer membrane protein of Escherichia coli K-12. The gene (ompA) for the major outer membrane protein II* from Escherichia coli K-12 has been cloned on a 5-megadalton EcoRI fragment by using phage lambda as vector. The gene is expressed during the lytic cycle of the recombinant phage and the insoluble membrane-bound protein was detected in phage plaques with a simple radioimmunoassay. Transfer of the EcoRI fragment into plasmid pSC101 and expression in a host lacking protein II* led to overproduction of protein II* and decreased production of two other major outer membrane proteins. Expression of the plasmid pSC101-ompA+ in minicells derived from an ompA minicell-producing strain led to synthesis, at high rates, of this protein and massive accumulation of a second cell envelope protein most likely representing the biosynthetic precursor of protein II*."} {"id": "PMID:159456", "title": "Cloning of integrated Moloney sarcoma proviral DNA sequences in bacteriophage lambda.", "content": "We have identified integrated proviral DNA sequences of m1 and HT-1 isolates of Moloney sarcoma virus (MuSV) in EcoRI digests of transformed mink cell genomic DNA and have cloned these fragments in bacteriophage lambda. Both the lambda-HT1 phage recombinant, containing a 12.3-kilobase MuSV pair (kb) fragment, and the lambda-m1 phage recombinant, containing a 7.0-kb fragment, possess full copies of the sarcoma viruses along with 5' and 3' host flanking sequences. The MuSV proviral DNA sequences, 6.7 kb for HT-1 and 5.2 kb for m1, are colinear by heteroduplex microscopy with the 1.5-kb difference in size accounted for by two approximately equal to 0.8-kb deleted regions in m1. Both integrated viral genomes are terminally redundant and have integrated at the same site in the provirus but at different sites on the host chromosome. The host sequence flanking integrated HT-1 MuSV have been identified as a single EcoRI restriction fragment of 5.6 kb in normal mink cells.", "contents": "Cloning of integrated Moloney sarcoma proviral DNA sequences in bacteriophage lambda. We have identified integrated proviral DNA sequences of m1 and HT-1 isolates of Moloney sarcoma virus (MuSV) in EcoRI digests of transformed mink cell genomic DNA and have cloned these fragments in bacteriophage lambda. Both the lambda-HT1 phage recombinant, containing a 12.3-kilobase MuSV pair (kb) fragment, and the lambda-m1 phage recombinant, containing a 7.0-kb fragment, possess full copies of the sarcoma viruses along with 5' and 3' host flanking sequences. The MuSV proviral DNA sequences, 6.7 kb for HT-1 and 5.2 kb for m1, are colinear by heteroduplex microscopy with the 1.5-kb difference in size accounted for by two approximately equal to 0.8-kb deleted regions in m1. Both integrated viral genomes are terminally redundant and have integrated at the same site in the provirus but at different sites on the host chromosome. The host sequence flanking integrated HT-1 MuSV have been identified as a single EcoRI restriction fragment of 5.6 kb in normal mink cells."} {"id": "PMID:159457", "title": "Isolation of glycosaminoglycans (heparan sulfate) from glomerular basement membranes.", "content": "Glycosaminoglycans were isolated from purified fractions of glomerular basement membranes and partially characterized by chemical analysis and cellulose acetate electrophoresis. Basement membranes were prepared by detergent treatment of rat glomeruli and subjected to digestion with papain and Pronase. Glycosaminoglycans were isolated from the digests by precipitation with cetyl pyridinium chloride and ethanol. Results of cellulose acetate electrophoresis of the isolated glycosaminoglycan fraction revealed the presence of one major and one minor spot. The major spot was identified as heparan sulfate because it comigrated with the heparan sulfate standard and was sensitive to heparinase and to nitrous acid oxidation but insensitive to chondroitinase ABC and to testicular or leech hyaluronidase. The minor spot was tentatively identified as hyaluronic acid based on its migratory behavior and sensitivity to leech and testicular hyaluronidase. The chemical composition of the isolated glycosaminoglycan was typical of that of heparan sulfate (high carbazole/orcinol ratio, high sulfate content, absence of galactosamine). The data support and confirm the cytochemical data obtained previously [Kanwar, Y. S. & Farquhar, M. G. (1979) Proc. Natl. Acad. Sci. USA 76, 1303-1307] demonstrating that heparan sulfate is the only sulfated glycosaminoglycan detectable in the glomerular basement membrane. The present results suggest that in addition to sulfated glycosaminoglycan some nonsulfated glycosaminoglycan (hyaluronic acid) may also be present in the glomerular basement membrane.", "contents": "Isolation of glycosaminoglycans (heparan sulfate) from glomerular basement membranes. Glycosaminoglycans were isolated from purified fractions of glomerular basement membranes and partially characterized by chemical analysis and cellulose acetate electrophoresis. Basement membranes were prepared by detergent treatment of rat glomeruli and subjected to digestion with papain and Pronase. Glycosaminoglycans were isolated from the digests by precipitation with cetyl pyridinium chloride and ethanol. Results of cellulose acetate electrophoresis of the isolated glycosaminoglycan fraction revealed the presence of one major and one minor spot. The major spot was identified as heparan sulfate because it comigrated with the heparan sulfate standard and was sensitive to heparinase and to nitrous acid oxidation but insensitive to chondroitinase ABC and to testicular or leech hyaluronidase. The minor spot was tentatively identified as hyaluronic acid based on its migratory behavior and sensitivity to leech and testicular hyaluronidase. The chemical composition of the isolated glycosaminoglycan was typical of that of heparan sulfate (high carbazole/orcinol ratio, high sulfate content, absence of galactosamine). The data support and confirm the cytochemical data obtained previously [Kanwar, Y. S. & Farquhar, M. G. (1979) Proc. Natl. Acad. Sci. USA 76, 1303-1307] demonstrating that heparan sulfate is the only sulfated glycosaminoglycan detectable in the glomerular basement membrane. The present results suggest that in addition to sulfated glycosaminoglycan some nonsulfated glycosaminoglycan (hyaluronic acid) may also be present in the glomerular basement membrane."} {"id": "PMID:159458", "title": "Lactose genes fused to exogenous promoters in one step using a Mu-lac bacteriophage: in vivo probe for transcriptional control sequences.", "content": "The lactose structural genes, without the lactose promoter, have been incorporated into the bacteriophage Mu genome to form a Mu-lac specialized transducing phage. This phage also carries a gene encoding resistance to ampicillin (Ap)[Mu(Ap, lac)]. After infection and upon establishment of lysogeny, the Mu(Ap, lac) genome can integrate into apparently random sites in the Escherichia coli chromosome. When integration occurs within a gene in the orientation of its transcription, the lactose structural genes are so situated that they become expressed solely from the promoter of that gene. Thus, expression of the lactose genes of Mu(Ap, lac) can be used as an assay for transcription of that gene and for functional and mutational studies of gene regulation.", "contents": "Lactose genes fused to exogenous promoters in one step using a Mu-lac bacteriophage: in vivo probe for transcriptional control sequences. The lactose structural genes, without the lactose promoter, have been incorporated into the bacteriophage Mu genome to form a Mu-lac specialized transducing phage. This phage also carries a gene encoding resistance to ampicillin (Ap)[Mu(Ap, lac)]. After infection and upon establishment of lysogeny, the Mu(Ap, lac) genome can integrate into apparently random sites in the Escherichia coli chromosome. When integration occurs within a gene in the orientation of its transcription, the lactose structural genes are so situated that they become expressed solely from the promoter of that gene. Thus, expression of the lactose genes of Mu(Ap, lac) can be used as an assay for transcription of that gene and for functional and mutational studies of gene regulation."} {"id": "PMID:159459", "title": "Transcription promotes recA-independent recombination mediated by DNA-dependent RNA polymerase in Escherichia coli.", "content": "The Rpo-mediated recombination of phage lambda takes place independently of the recA function and is promoted by DNA-dependent RNA polymerase of Escherichia coli [Ikeda, H. & Kobayashi, I. (1977) Proc. Natl. Acad Sci. USA 74, 3932--3936]. The crossovers were particularly frequent to the cIII-N and N-cII regions which are transcribed actively. To determine whether the transcription process required for the recombination is the initiation step or the chain elongation step, we have examined the effect of bacterial rho mutation, which affects transcription termination, on the distribution of crossover points in the lambda phage genome. The crossovers in the cII-S interval took place more frequently in rho mutant strains than in wild-type strains. Analysis of lambda mRNA showed that much more O-P-Q mRNA is synthesized in the rho mutant cells than in the wild-type cells and is largely produced by the readthrough from the PR promotor. These results strongly suggest that the chain elongation in transcription plays an essential role in this recombination. Physical analysis of the recombinant phage DNA showed that this recombination is a legitimate type. Models are presented to explain how the transcription complex can promote this recA-independent recombination.", "contents": "Transcription promotes recA-independent recombination mediated by DNA-dependent RNA polymerase in Escherichia coli. The Rpo-mediated recombination of phage lambda takes place independently of the recA function and is promoted by DNA-dependent RNA polymerase of Escherichia coli [Ikeda, H. & Kobayashi, I. (1977) Proc. Natl. Acad Sci. USA 74, 3932--3936]. The crossovers were particularly frequent to the cIII-N and N-cII regions which are transcribed actively. To determine whether the transcription process required for the recombination is the initiation step or the chain elongation step, we have examined the effect of bacterial rho mutation, which affects transcription termination, on the distribution of crossover points in the lambda phage genome. The crossovers in the cII-S interval took place more frequently in rho mutant strains than in wild-type strains. Analysis of lambda mRNA showed that much more O-P-Q mRNA is synthesized in the rho mutant cells than in the wild-type cells and is largely produced by the readthrough from the PR promotor. These results strongly suggest that the chain elongation in transcription plays an essential role in this recombination. Physical analysis of the recombinant phage DNA showed that this recombination is a legitimate type. Models are presented to explain how the transcription complex can promote this recA-independent recombination."} {"id": "PMID:159460", "title": "Sigma subunit of Escherichia coli RNA polymerase affects the function of lambda N gene.", "content": "A new class of Escherichia coli mutants, referred to as grn, has been isolated by localized mutagenesis. These mutations affect the sigma subunit of DNA-dependent RNA polymerase (ribonucleoside 5'-triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) by abolishing the expression of the lambda N gene, and they are closely lniked to dnaG in the order dnaG-grn-uxaA. Detailed study of one such mutant, grn1, yielded the following results: (i) grn1 is a single mutation and the mutant cell shows cold-sensitivity in growth; (ii) the Grn phenotype of the mutant can easily be suppressed by secondary mutations in the beta subunit gene of RNA polymerase; (iii) purified holoenzyme of RNA polymerase isolated from the mutant showed an altered salt-dependency in vitro, and the mixed reconstitution of the mutant with the wild-type subunits showed that the sigma subunit of the grn1 mutant is altered; (iv) lambda phage mutants (lambda grg), which overcome the grn mutation, can be classified into two groups, the \"nin-deletion\" and the \"N-mutant\" groups (both of these are also able to grow on the previously described groN mutant of Georgopoulos and nusAB of Friedman); (iv) the mutant polymerase transcribed 12S as well as 7S RNA from lambda DNA in the presence of the rho factor in vitro. These results indicate that the grn mutation alters the sigma subunit of RNA polymerase and that the sigma subunit participates in activating the N-mediated antitermination mode of lambda phage transcription.", "contents": "Sigma subunit of Escherichia coli RNA polymerase affects the function of lambda N gene. A new class of Escherichia coli mutants, referred to as grn, has been isolated by localized mutagenesis. These mutations affect the sigma subunit of DNA-dependent RNA polymerase (ribonucleoside 5'-triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) by abolishing the expression of the lambda N gene, and they are closely lniked to dnaG in the order dnaG-grn-uxaA. Detailed study of one such mutant, grn1, yielded the following results: (i) grn1 is a single mutation and the mutant cell shows cold-sensitivity in growth; (ii) the Grn phenotype of the mutant can easily be suppressed by secondary mutations in the beta subunit gene of RNA polymerase; (iii) purified holoenzyme of RNA polymerase isolated from the mutant showed an altered salt-dependency in vitro, and the mixed reconstitution of the mutant with the wild-type subunits showed that the sigma subunit of the grn1 mutant is altered; (iv) lambda phage mutants (lambda grg), which overcome the grn mutation, can be classified into two groups, the \"nin-deletion\" and the \"N-mutant\" groups (both of these are also able to grow on the previously described groN mutant of Georgopoulos and nusAB of Friedman); (iv) the mutant polymerase transcribed 12S as well as 7S RNA from lambda DNA in the presence of the rho factor in vitro. These results indicate that the grn mutation alters the sigma subunit of RNA polymerase and that the sigma subunit participates in activating the N-mediated antitermination mode of lambda phage transcription."} {"id": "PMID:159461", "title": "Bacterial lipopolysaccharide activates suppressor B lymphocytes.", "content": "Lipopolysaccharide (LPS) extracted from the outer cell wall of Gram-negative bacteria modulates the immune response in vivo and in vitro. Depending on the experimental conditions, it may enhance or inhibit the production of humoral antibody. The pathway by which LPS suppresses antibody production is examined in this study. C57BL/6 spleen cells incubated with LPS (greater than 10 micrograms/ml) not only fail to produce antibody to sheep erythrocytes in vitro but also, when transferred 24 hr after stimulation with LPS, inhibit antibody production in spleen cells that were not treated with LPS. This observation suggested that LPS activates suppressor cells. We have identified a suppressor B cell as mediator of LPS-induced immune suppression and determined its cell surface antigen phenotype as Ig+, Ia+, CR+, Ly-B-2+,PC1-.LPS does not induce suppressor macrophages or suppressor T cells, nor are macrophages or T cells required for the generation of suppressor B cells by LPS.", "contents": "Bacterial lipopolysaccharide activates suppressor B lymphocytes. Lipopolysaccharide (LPS) extracted from the outer cell wall of Gram-negative bacteria modulates the immune response in vivo and in vitro. Depending on the experimental conditions, it may enhance or inhibit the production of humoral antibody. The pathway by which LPS suppresses antibody production is examined in this study. C57BL/6 spleen cells incubated with LPS (greater than 10 micrograms/ml) not only fail to produce antibody to sheep erythrocytes in vitro but also, when transferred 24 hr after stimulation with LPS, inhibit antibody production in spleen cells that were not treated with LPS. This observation suggested that LPS activates suppressor cells. We have identified a suppressor B cell as mediator of LPS-induced immune suppression and determined its cell surface antigen phenotype as Ig+, Ia+, CR+, Ly-B-2+,PC1-.LPS does not induce suppressor macrophages or suppressor T cells, nor are macrophages or T cells required for the generation of suppressor B cells by LPS."} {"id": "PMID:159463", "title": "Effect of chinoform on the function of biological membranes.", "content": "To investigate the mechanism by which the toxic effect of chinoform (5-chloro-7-iodo-8-quinolinol) develops, its action on the function of biological membranes was examined. Findings were: 1. Chinoform induced K+ release from red cells. This effect was increased by prior addition of Mg2+ and decreased by albumin, ruthenium red, or lanthanum chloride. 2. Chinoform induced K+ release from isolated rat liver mitochondria more effectively in the presence of Mg2+ or other bivalent cations, and a chinoform-Mg chelate was more effective than chinoform alone. The K+ release from mitochondria was protected by albumin and to a certain extent by lanthanum chloride. 3. The change in the ion permeability of mitochondrial membrane induced by chinoform in the presence of Mg2+ was accompanied by uncoupling of the oxidative phosphorylation. These results suggest that chinoform interacts with membranes more effectively as a metal chelate, producing conformational and functional changes in those membranes.", "contents": "Effect of chinoform on the function of biological membranes. To investigate the mechanism by which the toxic effect of chinoform (5-chloro-7-iodo-8-quinolinol) develops, its action on the function of biological membranes was examined. Findings were: 1. Chinoform induced K+ release from red cells. This effect was increased by prior addition of Mg2+ and decreased by albumin, ruthenium red, or lanthanum chloride. 2. Chinoform induced K+ release from isolated rat liver mitochondria more effectively in the presence of Mg2+ or other bivalent cations, and a chinoform-Mg chelate was more effective than chinoform alone. The K+ release from mitochondria was protected by albumin and to a certain extent by lanthanum chloride. 3. The change in the ion permeability of mitochondrial membrane induced by chinoform in the presence of Mg2+ was accompanied by uncoupling of the oxidative phosphorylation. These results suggest that chinoform interacts with membranes more effectively as a metal chelate, producing conformational and functional changes in those membranes."} {"id": "PMID:159478", "title": "[Surgical treatment of calcanear fractures (103 cases). Reconstruction-arthrodesis, or reconstruction (author's transl)].", "content": "In a twelve-year period, 103 calcanear fractures (thalamus) were operated on, either by the Stulz procedure (calcanear Reconstruction-subtalar Arthrodesis [83 cases]), or by Reconstruction (20 cases). During the first seven years, the Stulz procedure had been performed systematically. During the following five years, indications were shaded between 28 reconstruction-arthrodesis and 20 reconstructions. A complete preoperative radiological study, including especially horizontal calcanear tomography enables to precise what type of injuries affects the four different parts of the calcaneus, and to choose between either procedure.", "contents": "[Surgical treatment of calcanear fractures (103 cases). Reconstruction-arthrodesis, or reconstruction (author's transl)]. In a twelve-year period, 103 calcanear fractures (thalamus) were operated on, either by the Stulz procedure (calcanear Reconstruction-subtalar Arthrodesis [83 cases]), or by Reconstruction (20 cases). During the first seven years, the Stulz procedure had been performed systematically. During the following five years, indications were shaded between 28 reconstruction-arthrodesis and 20 reconstructions. A complete preoperative radiological study, including especially horizontal calcanear tomography enables to precise what type of injuries affects the four different parts of the calcaneus, and to choose between either procedure."} {"id": "PMID:159484", "title": "[Down syndrome: immunological study in adults (author's transl)].", "content": "The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome.", "contents": "[Down syndrome: immunological study in adults (author's transl)]. The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome."} {"id": "PMID:159485", "title": "[Hypothyroid myopathy: histochemical and ultrastructural features with physiopatological correlations (author's transl)].", "content": "The Authors describe an adult case of hypothyroid myopathy which occurred after a Hashimoto's thyroiditis. Ultrastructural examination of the deltoid muscle showed two fundamental changes: 1) large collections of mitochondria generally normal in shape, structure and size, especially in the subsarcolemmal sapce of the muscle fibre; 2) glycogen deposits both beneath sarcolemmal membrane and between myofibrils. Histochemical examination reveals an increased activity of mitochondrial oxydative enzymes, such as NADPH and SDH especially in subsarcolemmal regions of many type I fibres. The histogram is normal. It seems that the multiplication of skeletal muscle mitochondria may be compensatory to the slowing down of metabolic activities. This, however, is ineffective because it involves the mitochondria localized more superficially in the fibres with a loosely coupled oxydative phosphorylation. Glycogen accumulations are probably due to deficiency of the thyroid hormone; in fact stimulation of carbohydrate metabolism by thyroxine is well known. The abnormal functioning of the muscular mitochondria and the defective utilisation of glycogen are the most important factors in the pathogenesis of muscular weakness of hypothyroid myopathy.", "contents": "[Hypothyroid myopathy: histochemical and ultrastructural features with physiopatological correlations (author's transl)]. The Authors describe an adult case of hypothyroid myopathy which occurred after a Hashimoto's thyroiditis. Ultrastructural examination of the deltoid muscle showed two fundamental changes: 1) large collections of mitochondria generally normal in shape, structure and size, especially in the subsarcolemmal sapce of the muscle fibre; 2) glycogen deposits both beneath sarcolemmal membrane and between myofibrils. Histochemical examination reveals an increased activity of mitochondrial oxydative enzymes, such as NADPH and SDH especially in subsarcolemmal regions of many type I fibres. The histogram is normal. It seems that the multiplication of skeletal muscle mitochondria may be compensatory to the slowing down of metabolic activities. This, however, is ineffective because it involves the mitochondria localized more superficially in the fibres with a loosely coupled oxydative phosphorylation. Glycogen accumulations are probably due to deficiency of the thyroid hormone; in fact stimulation of carbohydrate metabolism by thyroxine is well known. The abnormal functioning of the muscular mitochondria and the defective utilisation of glycogen are the most important factors in the pathogenesis of muscular weakness of hypothyroid myopathy."} {"id": "PMID:159480", "title": "[The treatment of spastic equinovarus in the adult by transplantation of peroneus brevis and lengthening of the tendo-calcaneus (author's transl)].", "content": "A new technique is proposed for the treatment of spastic equinovarus foot. After lengthening the tendo calcaneus, the peroneus brevis tendon is divided at the junction with its muscle belly and the distal end of the tendon is transferred through the interosseous membrane to be sutured to the tendo calcaneus. This technique aims to correct the varus as well as the equinus deformity. It was performed in seven cases with good results. The technique is compared with other methods designed to treat this condition. The method is worthwhile in cases without bony deformity.", "contents": "[The treatment of spastic equinovarus in the adult by transplantation of peroneus brevis and lengthening of the tendo-calcaneus (author's transl)]. A new technique is proposed for the treatment of spastic equinovarus foot. After lengthening the tendo calcaneus, the peroneus brevis tendon is divided at the junction with its muscle belly and the distal end of the tendon is transferred through the interosseous membrane to be sutured to the tendo calcaneus. This technique aims to correct the varus as well as the equinus deformity. It was performed in seven cases with good results. The technique is compared with other methods designed to treat this condition. The method is worthwhile in cases without bony deformity."} {"id": "PMID:159479", "title": "[A nerve root anomaly with lumbar disc prolapse. Report of a case (author's transl)].", "content": "A case of sciatica with partial paralysis of both lower limbs is reported. At operation a prolapse of the L4/5 intervertebral disc on the right side was associated with an anomaly of the left fifth lumbar root which was lower and more horizontal than normal. The authors give a short review of the literature.", "contents": "[A nerve root anomaly with lumbar disc prolapse. Report of a case (author's transl)]. A case of sciatica with partial paralysis of both lower limbs is reported. At operation a prolapse of the L4/5 intervertebral disc on the right side was associated with an anomaly of the left fifth lumbar root which was lower and more horizontal than normal. The authors give a short review of the literature."} {"id": "PMID:159487", "title": "[Suppressor cells of mitogen responses during rheumatoid polyarthritis].", "content": "The suppressor activity of mononuclear cells of the peripheral blood (MCPB) during rheumatoid polyarthritis (RP) was studied using experimental protocole. The MCPB stimulated in vitro by concanavaline A (Con A) are capable of suppressing the mitogenis response of autologus cells; moreover, the short-lived spontaneous suppressor cells disappear during 24 hour in vitro incubation that determines an increase in the proliferative response of the incubated cells for 24 hours. In two of the six RP studied, the suppressor activity generated Con A and the spontaneous suppressor activity are nul. Culture experiments with the MCPB of PR and control subjects show that this defect in suppressor activity is more related to a problem in the generation of suppressor cells than to a deficiency in the response to suppressor signals.", "contents": "[Suppressor cells of mitogen responses during rheumatoid polyarthritis]. The suppressor activity of mononuclear cells of the peripheral blood (MCPB) during rheumatoid polyarthritis (RP) was studied using experimental protocole. The MCPB stimulated in vitro by concanavaline A (Con A) are capable of suppressing the mitogenis response of autologus cells; moreover, the short-lived spontaneous suppressor cells disappear during 24 hour in vitro incubation that determines an increase in the proliferative response of the incubated cells for 24 hours. In two of the six RP studied, the suppressor activity generated Con A and the spontaneous suppressor activity are nul. Culture experiments with the MCPB of PR and control subjects show that this defect in suppressor activity is more related to a problem in the generation of suppressor cells than to a deficiency in the response to suppressor signals."} {"id": "PMID:159488", "title": "[Study of the allogenic reactivity and suppression function of lymphocytes, in rheumatoid polyarthritis treated with cold salts, in mixed lymphocyte cultures].", "content": "In a group of 30 rheumatoid polyarthritis treated with gold salts, a determination of the T lymphocytes (sheep red cells) furnished in percentage normal values, and in absolute value a normal average value, with, however, a low level of T lymphocytes. In autologous lymphocyte cultures no spontaneous increase of DNA synthesis was registered. The allogenic response was normal, and in mixed culture with the addition of a third type of cells, a discrete specific suppressive activity appeared.", "contents": "[Study of the allogenic reactivity and suppression function of lymphocytes, in rheumatoid polyarthritis treated with cold salts, in mixed lymphocyte cultures]. In a group of 30 rheumatoid polyarthritis treated with gold salts, a determination of the T lymphocytes (sheep red cells) furnished in percentage normal values, and in absolute value a normal average value, with, however, a low level of T lymphocytes. In autologous lymphocyte cultures no spontaneous increase of DNA synthesis was registered. The allogenic response was normal, and in mixed culture with the addition of a third type of cells, a discrete specific suppressive activity appeared."} {"id": "PMID:159491", "title": "Severe hypersensitivity reactions to allopurinol.", "content": "The frequency of severe reactions to allopurinol has probably been underestimated. A retrospective study encompassing a five-year period has yielded 20 patients with severe hypersensitivity reactions to allopurinol. Patients with preexisting renal impairment or who were receiving concomitant thiazide diuretics appeared to be especially predisposed. Cutaneous reaction patterns included maculopapular eruptions, exfoliative dermatitis, and toxic epidermal necrolysis. eosinophilia was uncommon. Forty percent of the patients developed hepatic involvement and 45% had renal involvement. Hepatic and renal changes usually were reversible and were not unique to any one cutaneous reaction pattern. Three patients with renal involvement required prolonged administration of systemic steroids. Complications included sepsis, decubitus ulcers, and thromboembolism. Two patients required hyperalimentation. Sequelae included dry eyes, pigmentary disturbances, and keloids. Three patients died as a result of their reaction. It is concluded that allopurinol should be used only in select patients, and the dosage should be modified if renal disease exists.", "contents": "Severe hypersensitivity reactions to allopurinol. The frequency of severe reactions to allopurinol has probably been underestimated. A retrospective study encompassing a five-year period has yielded 20 patients with severe hypersensitivity reactions to allopurinol. Patients with preexisting renal impairment or who were receiving concomitant thiazide diuretics appeared to be especially predisposed. Cutaneous reaction patterns included maculopapular eruptions, exfoliative dermatitis, and toxic epidermal necrolysis. eosinophilia was uncommon. Forty percent of the patients developed hepatic involvement and 45% had renal involvement. Hepatic and renal changes usually were reversible and were not unique to any one cutaneous reaction pattern. Three patients with renal involvement required prolonged administration of systemic steroids. Complications included sepsis, decubitus ulcers, and thromboembolism. Two patients required hyperalimentation. Sequelae included dry eyes, pigmentary disturbances, and keloids. Three patients died as a result of their reaction. It is concluded that allopurinol should be used only in select patients, and the dosage should be modified if renal disease exists."} {"id": "PMID:159492", "title": "Subclavian steal syndrome: an update.", "content": "The clinical findings in this series of 22 cases of subclavian steal syndrome showed a predominance of men (13:9), a mean age of 51 years, and a predominance of left subclavian artery obstruction. There was a blood pressure differential of more than 20 mm Hg and diminished pulses ipsilaterally in most. Main indications for surgical repair were transient neurologic symptoms. Twenty-one of our patients had surgical repair of the subclavian steal syndrome; six had concomitant carotid artery surgery. The most common surgical procedure performed consisted of a carotid subclavian bypass graft. One patient had only carotid revascularization; 19 patients have had good long-term results. One patient, with tetralogy, died and three had complications. The asymptomatic or mildly symptomatic patient may be given a trial of medical treatment. Symptomatic patients can have extrathoracic bypass with a very low risk. Surgery is indicated if significant associated carotid lesions are present.", "contents": "Subclavian steal syndrome: an update. The clinical findings in this series of 22 cases of subclavian steal syndrome showed a predominance of men (13:9), a mean age of 51 years, and a predominance of left subclavian artery obstruction. There was a blood pressure differential of more than 20 mm Hg and diminished pulses ipsilaterally in most. Main indications for surgical repair were transient neurologic symptoms. Twenty-one of our patients had surgical repair of the subclavian steal syndrome; six had concomitant carotid artery surgery. The most common surgical procedure performed consisted of a carotid subclavian bypass graft. One patient had only carotid revascularization; 19 patients have had good long-term results. One patient, with tetralogy, died and three had complications. The asymptomatic or mildly symptomatic patient may be given a trial of medical treatment. Symptomatic patients can have extrathoracic bypass with a very low risk. Surgery is indicated if significant associated carotid lesions are present."} {"id": "PMID:159501", "title": "Gas-liquid chromatographic analysis of urinary steroids.", "content": "A method for gas-liquid chromatographic separation and quantitation of urinary steroid metabolites is described. A normal reference range has been established and classic examples of urinary steroid profiles of the major steroid disorders are given.", "contents": "Gas-liquid chromatographic analysis of urinary steroids. A method for gas-liquid chromatographic separation and quantitation of urinary steroid metabolites is described. A normal reference range has been established and classic examples of urinary steroid profiles of the major steroid disorders are given."} {"id": "PMID:159502", "title": "The use of vasodilator agents in the treatment of heart failure.", "content": "In cardiac failure unresponsive to digoxin and diuretics, afterload reduction brings about a dramatic increase in cardiac output, renal perfusion and responsiveness to diuretics; furthermore, the decrease in venous pressure relieves the dyspnoea. Intravenous vasodilators should only be used when sophisticated haemodynamic monitoring equipment and experienced physicians are at hand. Indications for the use of these agents are severe cardiac failure, acute myocardial infarction complicated by left ventricular failure, persistent ischaemic pain and limitation of infarct size. A wide variety of oral vasodilator agents is available, all having different sites of action; the choice of vasodilator agents should be tailored to the needs of the patient. Treatment with these agents is indicated in patients in whom cardiac failure becomes refractory to conventional therapy with digoxin and diuretics. The utmost care must be taken to avoid further impairment of cardiac output by excessive reduction of the left ventricular end-diastolic pressure (LVEDP) and hypotension, which will jeopardize myocardial, renal and cerebral perfusion.", "contents": "The use of vasodilator agents in the treatment of heart failure. In cardiac failure unresponsive to digoxin and diuretics, afterload reduction brings about a dramatic increase in cardiac output, renal perfusion and responsiveness to diuretics; furthermore, the decrease in venous pressure relieves the dyspnoea. Intravenous vasodilators should only be used when sophisticated haemodynamic monitoring equipment and experienced physicians are at hand. Indications for the use of these agents are severe cardiac failure, acute myocardial infarction complicated by left ventricular failure, persistent ischaemic pain and limitation of infarct size. A wide variety of oral vasodilator agents is available, all having different sites of action; the choice of vasodilator agents should be tailored to the needs of the patient. Treatment with these agents is indicated in patients in whom cardiac failure becomes refractory to conventional therapy with digoxin and diuretics. The utmost care must be taken to avoid further impairment of cardiac output by excessive reduction of the left ventricular end-diastolic pressure (LVEDP) and hypotension, which will jeopardize myocardial, renal and cerebral perfusion."} {"id": "PMID:159503", "title": "Effect of rehabilitation on employment and earnings of the disabled: sociodemographic factors.", "content": "This report analyzes the importance of sociodemographic factors in the effect of rehabilitation services on the employment and earnings of disabled persons after their cases were closed by State vocational rehabilitation agencies in fiscal year 1971. The analysis is based on information about personal characteristics and on 1972 employment and earnings data for all such cases in the linked records of the Social Security Administration and the Rehabilitation Services Administration. It identifies sociodemographic factors that facilitate or hamper the effects of rehabilitation as measured primarily by employment differences between clients who completed and failed to complete a program of rehabilitation services. Rehabilitation appears to provide aid, especially to groups frequently disadvantaged in the labor market because of sex, age, ethnicity, or education. Impact was greater for men--but not for women--who were married and had larger families. These results differe significantly from conclusions based on previous studies of the disabled. Earlier studies often concluded that vocational rehabilitation was less successful for women, older persons, ethnic minorities, and persons with low socioeconomic status. Because those studies lacked information on rehabilitation status or focused only on persons who had received rehabilitation services and because they did not compare those who had completed a rehabilitation program with those who had not, they were unable to examine the effects of vocational rehabilitation completely.", "contents": "Effect of rehabilitation on employment and earnings of the disabled: sociodemographic factors. This report analyzes the importance of sociodemographic factors in the effect of rehabilitation services on the employment and earnings of disabled persons after their cases were closed by State vocational rehabilitation agencies in fiscal year 1971. The analysis is based on information about personal characteristics and on 1972 employment and earnings data for all such cases in the linked records of the Social Security Administration and the Rehabilitation Services Administration. It identifies sociodemographic factors that facilitate or hamper the effects of rehabilitation as measured primarily by employment differences between clients who completed and failed to complete a program of rehabilitation services. Rehabilitation appears to provide aid, especially to groups frequently disadvantaged in the labor market because of sex, age, ethnicity, or education. Impact was greater for men--but not for women--who were married and had larger families. These results differe significantly from conclusions based on previous studies of the disabled. Earlier studies often concluded that vocational rehabilitation was less successful for women, older persons, ethnic minorities, and persons with low socioeconomic status. Because those studies lacked information on rehabilitation status or focused only on persons who had received rehabilitation services and because they did not compare those who had completed a rehabilitation program with those who had not, they were unable to examine the effects of vocational rehabilitation completely."} {"id": "PMID:159505", "title": "Synchronous aortofemoral or iliofemoral bypass with revascularization of the lower extremity.", "content": "Bypassing aortoiliac stenosing lesions to the profunda femoria alone, even with extensive end-arterectomy and angioplasty of the latter, will not provide predictable excellent results in the presence of gangrene and occlusion in the femoral popliteal system. With severe pregangrene and rest pain, residual ischemic complaints are also common, and if lesions are present, healing is incomplete or, at best, delayed. Alternatively, femoropopliteal or tibial bypass, in the presence of even moderately diminished inflow, is subject to either early or delayed closure, unless proximal repair is also performed in appropriately selected patients. Synchronous correction of tandem lesions involving the aortoiliac and femoropopliteal segments should, therefore, be considered for limb salvage only and particularly in the presence of focal gangrene, excision or debridement of which can be anticipated to heal after successful bypass. Major diminution in femoral inflow usually indicates the need for proximal repair only, even in the presence of distal lesions. Noninvasive studies and intraoperative flow determinations are not uniformly helpful in patient selection. Synchronous aortofemoral or iliofemoral and femoropopliteal or tibial reconstructions were performed upon 38 patients, 15 of whom had no prior vascular operation and 23 of whom had previously undergone either aortofemoral or femoropopliteal bypasses that had failed. Graft patency for all patients was 76 per cent, and although it was better for the patients in group 1 than for those in group 2, no statistical significance existed between the two groups. Improved patient selection and criteria for performing synchronous reconstructions might originally have been of benefit for the patients in group 2, avoiding more difficult secondary repairs. It must be emphasized, however, that synchronous reconstructions should not be done routinely in the presence of multilevel disease. Rather, specific indications do exist and should be considered on an individual basis.", "contents": "Synchronous aortofemoral or iliofemoral bypass with revascularization of the lower extremity. Bypassing aortoiliac stenosing lesions to the profunda femoria alone, even with extensive end-arterectomy and angioplasty of the latter, will not provide predictable excellent results in the presence of gangrene and occlusion in the femoral popliteal system. With severe pregangrene and rest pain, residual ischemic complaints are also common, and if lesions are present, healing is incomplete or, at best, delayed. Alternatively, femoropopliteal or tibial bypass, in the presence of even moderately diminished inflow, is subject to either early or delayed closure, unless proximal repair is also performed in appropriately selected patients. Synchronous correction of tandem lesions involving the aortoiliac and femoropopliteal segments should, therefore, be considered for limb salvage only and particularly in the presence of focal gangrene, excision or debridement of which can be anticipated to heal after successful bypass. Major diminution in femoral inflow usually indicates the need for proximal repair only, even in the presence of distal lesions. Noninvasive studies and intraoperative flow determinations are not uniformly helpful in patient selection. Synchronous aortofemoral or iliofemoral and femoropopliteal or tibial reconstructions were performed upon 38 patients, 15 of whom had no prior vascular operation and 23 of whom had previously undergone either aortofemoral or femoropopliteal bypasses that had failed. Graft patency for all patients was 76 per cent, and although it was better for the patients in group 1 than for those in group 2, no statistical significance existed between the two groups. Improved patient selection and criteria for performing synchronous reconstructions might originally have been of benefit for the patients in group 2, avoiding more difficult secondary repairs. It must be emphasized, however, that synchronous reconstructions should not be done routinely in the presence of multilevel disease. Rather, specific indications do exist and should be considered on an individual basis."} {"id": "PMID:159510", "title": "Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction.", "content": "The effects of (a) regular use for one week and (b) a single dose of a synthetic anticholinergic (ipratropium bromide) on lung mucociliary clearance and as a bronchodilator was ascertained in a controlled, double-blind, cross-over study in 12 patients with reversible airways obstruction (mean increase in FEV after isoprenaline: 17% range 10-50%). Two puffs from a metered dose inhaler of either placebo (propellants only) or drug (40 microgram) were administered four times a day for one week (regular use), and mucociliary clearance was measured, by radioaerosol tracer, at the end of each treatment period and after a control period in which no treatment was given. On the mornings of the measurements after the placebo and drug periods one final dose (single dose) of ipratropium (40 microgram) or placebo was given 2.5 hours before the start of the test. There was no statistically significant difference between the three mean mucociliary clearance curves (control, placebo, and drug) for the group; however, there was a significantly greater penetration towards the periphery of the lung of the tracer in the test after drug administration compared with the other two. This increased penetration was attributed to bronchodilatation caused by the drug. Ipratropium bromide does not appear to impair mucociliary clearance, and it acts an effective bronchodilator.", "contents": "Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction. The effects of (a) regular use for one week and (b) a single dose of a synthetic anticholinergic (ipratropium bromide) on lung mucociliary clearance and as a bronchodilator was ascertained in a controlled, double-blind, cross-over study in 12 patients with reversible airways obstruction (mean increase in FEV after isoprenaline: 17% range 10-50%). Two puffs from a metered dose inhaler of either placebo (propellants only) or drug (40 microgram) were administered four times a day for one week (regular use), and mucociliary clearance was measured, by radioaerosol tracer, at the end of each treatment period and after a control period in which no treatment was given. On the mornings of the measurements after the placebo and drug periods one final dose (single dose) of ipratropium (40 microgram) or placebo was given 2.5 hours before the start of the test. There was no statistically significant difference between the three mean mucociliary clearance curves (control, placebo, and drug) for the group; however, there was a significantly greater penetration towards the periphery of the lung of the tracer in the test after drug administration compared with the other two. This increased penetration was attributed to bronchodilatation caused by the drug. Ipratropium bromide does not appear to impair mucociliary clearance, and it acts an effective bronchodilator."} {"id": "PMID:159511", "title": "Action of brinase on human fibrinogen and plasminogen.", "content": "Brinase added to human plasma in vitro caused a decrease in fibrinogen concentration, positive paracoagulation tests and formation of a friable clot in sequence. Agarose gel filtration of these samples revealed the presence of fibrinogen derivatives both larger and smaller than the parent molecule. Infusion of the enzyme in vivo resulted in a decreased fibrinogen level, a prolonged thrombin time and an increase in fibrinogen related antigen (FRA) in serum. The elution pattern of FRA in the plasma samples obtained after infusion of Brinase was similar to that of the in vitro samples. The plasma pool of fibrinogen was partially consumed by infusion of Brinase, but the turnover of plasminogen remained unaffected. Purified plasminogen was partially degraded by addition of the enzyme but this was accompanied by a generation of proteolytic activity. These findings confirm that Brinase induces a proteolytic degradation of fibrinogen in plasma without activation of the plasminogen-plasmin system. Exposure of polymerization site(s) in the fibrinogen molecule is probably responsible for the reported clot promoting effect of the enzyme.", "contents": "Action of brinase on human fibrinogen and plasminogen. Brinase added to human plasma in vitro caused a decrease in fibrinogen concentration, positive paracoagulation tests and formation of a friable clot in sequence. Agarose gel filtration of these samples revealed the presence of fibrinogen derivatives both larger and smaller than the parent molecule. Infusion of the enzyme in vivo resulted in a decreased fibrinogen level, a prolonged thrombin time and an increase in fibrinogen related antigen (FRA) in serum. The elution pattern of FRA in the plasma samples obtained after infusion of Brinase was similar to that of the in vitro samples. The plasma pool of fibrinogen was partially consumed by infusion of Brinase, but the turnover of plasminogen remained unaffected. Purified plasminogen was partially degraded by addition of the enzyme but this was accompanied by a generation of proteolytic activity. These findings confirm that Brinase induces a proteolytic degradation of fibrinogen in plasma without activation of the plasminogen-plasmin system. Exposure of polymerization site(s) in the fibrinogen molecule is probably responsible for the reported clot promoting effect of the enzyme."} {"id": "PMID:159512", "title": "The plasminogen content of commercial preparations and of normal donor plasma in relation to the plasmin content of the 1st international plasmin reference preparation.", "content": "Kabi human plasminogen and plasmin and two Behringwerke preparations of human plasminogen were examined for antigen content, purity and specific activity with the 1st International W.H.O. human plasmin reference preparation and with the plasminogen content of an 8 donor normal plasma pool. In relation to the plasminogen content of the preparation with the highest specific activity, the 8 donor plasma pool contained 0.186 mg/ml of plasminogen. This plasminogen on complete conversion to plasmin by streptokinase or urokinase corresponded to 4.35 International units/ml of plasmin as defined by the International reference preparation. Protein adsorption from highly purified plasminogens of low protein content induced variable underestimates of antigen and of biological activity. To prevent this it is recommended to issue these purified preparations in an inert carrier medium or alternatively to release these preparations with data pertaining to salt content and optical measurement prior to lyophilisation. When standards of high purity and low protein content are being examined for antigen and enzyme, it is recommended likewise that an inert protein carrier should be present in the diluent. Measurement of proactivator was considered to be unsuitable in reference to proactivator content of highly purified plasmin and plasminogen.", "contents": "The plasminogen content of commercial preparations and of normal donor plasma in relation to the plasmin content of the 1st international plasmin reference preparation. Kabi human plasminogen and plasmin and two Behringwerke preparations of human plasminogen were examined for antigen content, purity and specific activity with the 1st International W.H.O. human plasmin reference preparation and with the plasminogen content of an 8 donor normal plasma pool. In relation to the plasminogen content of the preparation with the highest specific activity, the 8 donor plasma pool contained 0.186 mg/ml of plasminogen. This plasminogen on complete conversion to plasmin by streptokinase or urokinase corresponded to 4.35 International units/ml of plasmin as defined by the International reference preparation. Protein adsorption from highly purified plasminogens of low protein content induced variable underestimates of antigen and of biological activity. To prevent this it is recommended to issue these purified preparations in an inert carrier medium or alternatively to release these preparations with data pertaining to salt content and optical measurement prior to lyophilisation. When standards of high purity and low protein content are being examined for antigen and enzyme, it is recommended likewise that an inert protein carrier should be present in the diluent. Measurement of proactivator was considered to be unsuitable in reference to proactivator content of highly purified plasmin and plasminogen."} {"id": "PMID:159513", "title": "Kinetic studies on the selectivity of a synthetic thrombin-inhibitor using synthetic peptide substrates.", "content": "The synthetic thrombin-inhibitor termed No. 205 (N-alpha-dansyl-L-arginine-4-ethyl-piperidine amide) found in our laboratories was studied kinetically using synthetic peptide substrates. The following results were obtained. 1. No. 205 inhibited thrombin competively with bz-Phe-Val-Arg-pNA and the Ki value obtained was extremely small, 3.7 x 10(-8) M. 2. No. 205 also inhibited trypsin competitively with bz-Phe-Val-Arg-pNA but the Ki value obtained was far larger than that for thrombin, 1.0 x 10(-5) M. 3. No. 205 inhibited F. Xa, plasmin and urokinase only to a small extent when estimated using 2 x 10(-4) M D-Val-Leu-Lys-pNA, bz-Ile-Glu-Gly-Arg-pNA and Glu-Gly-Arg-pNA, respectively. 4. No 205 differed from APPA in its specific inhibitory spectrum for thrombin as compared to trypsin, plasmin and F. Xa. The above results indicate that No. 205 is an extremely potent and highly selective reversible thrombin-inhibitor.", "contents": "Kinetic studies on the selectivity of a synthetic thrombin-inhibitor using synthetic peptide substrates. The synthetic thrombin-inhibitor termed No. 205 (N-alpha-dansyl-L-arginine-4-ethyl-piperidine amide) found in our laboratories was studied kinetically using synthetic peptide substrates. The following results were obtained. 1. No. 205 inhibited thrombin competively with bz-Phe-Val-Arg-pNA and the Ki value obtained was extremely small, 3.7 x 10(-8) M. 2. No. 205 also inhibited trypsin competitively with bz-Phe-Val-Arg-pNA but the Ki value obtained was far larger than that for thrombin, 1.0 x 10(-5) M. 3. No. 205 inhibited F. Xa, plasmin and urokinase only to a small extent when estimated using 2 x 10(-4) M D-Val-Leu-Lys-pNA, bz-Ile-Glu-Gly-Arg-pNA and Glu-Gly-Arg-pNA, respectively. 4. No 205 differed from APPA in its specific inhibitory spectrum for thrombin as compared to trypsin, plasmin and F. Xa. The above results indicate that No. 205 is an extremely potent and highly selective reversible thrombin-inhibitor."} {"id": "PMID:159515", "title": "Comparative histochemical studies on fibrinolysis in whole organs and isolated tissue layers.", "content": "Using Todd's technique for the detection of plasminogen activator and Noordhoek Hegt and Brakman's method for inhibitors of fibrinolysis, rat tissues were studied, both in sections of whole organs and as separated tissue layers. Whole organ preparations showed less fibrinolytic activity and poorer localisation of inhibitor, because of a widespread diffusion of the inhibitor from tissue layers rich in inhibitor during the histochemical procedures. It is concluded that when using histochemical methods both agents are best studied in separated layers of the organ to avoid the masking effects of diffused inhibitor.", "contents": "Comparative histochemical studies on fibrinolysis in whole organs and isolated tissue layers. Using Todd's technique for the detection of plasminogen activator and Noordhoek Hegt and Brakman's method for inhibitors of fibrinolysis, rat tissues were studied, both in sections of whole organs and as separated tissue layers. Whole organ preparations showed less fibrinolytic activity and poorer localisation of inhibitor, because of a widespread diffusion of the inhibitor from tissue layers rich in inhibitor during the histochemical procedures. It is concluded that when using histochemical methods both agents are best studied in separated layers of the organ to avoid the masking effects of diffused inhibitor."} {"id": "PMID:159523", "title": "Ineffectiveness of the Doppler Ophthalmic Test (DOT) in post-endarterectomy evaluation.", "content": "In an effort to evaluate the effectiveness of the Doppler Ophthalmic Test (DOT) following carotid endarterectomy, a large group of patients was examined both pre- and postoperatively with non-invasive techniques. The DOT, which has proven to be a useful non-invasive diagnostic test for the determination of significant carotid artery stenosis, was found to be persistently abnormal in 46% of patients with a preoperative positive test. This occurred in spite of the fact that operative arteriography, direct ultrasonic auscultation, and Doppler imaging studies were all within normal limits. It is suggested from this study that the Doppler Ophthalmic Test alone is not adequate to follow patients postoperatively, especially if an abnormal study persists following a satisfactory endarterectomy. Other non-invasive techniques, which employ direct ultrasonic imaging of the carotid flow, may be more accurate in determining vessel patency.", "contents": "Ineffectiveness of the Doppler Ophthalmic Test (DOT) in post-endarterectomy evaluation. In an effort to evaluate the effectiveness of the Doppler Ophthalmic Test (DOT) following carotid endarterectomy, a large group of patients was examined both pre- and postoperatively with non-invasive techniques. The DOT, which has proven to be a useful non-invasive diagnostic test for the determination of significant carotid artery stenosis, was found to be persistently abnormal in 46% of patients with a preoperative positive test. This occurred in spite of the fact that operative arteriography, direct ultrasonic auscultation, and Doppler imaging studies were all within normal limits. It is suggested from this study that the Doppler Ophthalmic Test alone is not adequate to follow patients postoperatively, especially if an abnormal study persists following a satisfactory endarterectomy. Other non-invasive techniques, which employ direct ultrasonic imaging of the carotid flow, may be more accurate in determining vessel patency."} {"id": "PMID:159530", "title": "A new modulation method with range resolution for ultrasonic Doppler flow sensing.", "content": "This paper proposes a new pair of sequences whose cross-correlation values are zero except for the peak value and presents a new modulation method for an ultrasonic Doppler flowmeter with high sensitivity utilizing these sequences. In this method, transmitted and received waves are modulated and demodulated, respectively, by the specified new sequences. Since ulfavourable reflected waves can be almost completely eliminated by this proposed modulation method, a high signal-to-noise ratio is easily achieved. Elementary experimental results are also given.", "contents": "A new modulation method with range resolution for ultrasonic Doppler flow sensing. This paper proposes a new pair of sequences whose cross-correlation values are zero except for the peak value and presents a new modulation method for an ultrasonic Doppler flowmeter with high sensitivity utilizing these sequences. In this method, transmitted and received waves are modulated and demodulated, respectively, by the specified new sequences. Since ulfavourable reflected waves can be almost completely eliminated by this proposed modulation method, a high signal-to-noise ratio is easily achieved. Elementary experimental results are also given."} {"id": "PMID:159534", "title": "[Diagnosis and the surgical treatment of tumors of the anterior abdominal wall].", "content": "In 1015 patients with various diseases of soft tissues the pathological process was localized in the anterior abdominal wall in 64 patients (6,3%): desmoids were found in 41 patients, sarcomas -- in 12, benign tumors -- in 5 and non-tumor diseases -- in 6 patients. Dissection of the tumor must be performed not less than 2 -- 3 cm further than the pulpated borders. When plasty with local tissues is not possible, it is expedient to employ synthetic (terylene) prostheses.", "contents": "[Diagnosis and the surgical treatment of tumors of the anterior abdominal wall]. In 1015 patients with various diseases of soft tissues the pathological process was localized in the anterior abdominal wall in 64 patients (6,3%): desmoids were found in 41 patients, sarcomas -- in 12, benign tumors -- in 5 and non-tumor diseases -- in 6 patients. Dissection of the tumor must be performed not less than 2 -- 3 cm further than the pulpated borders. When plasty with local tissues is not possible, it is expedient to employ synthetic (terylene) prostheses."} {"id": "PMID:159541", "title": "Glomerular localization of preformed immune complexes in nephrotoxic serum nephritis.", "content": "Pre-formed immune complexes solubilized in antigen excess were infused into rats with nephrotoxic serum nephritis and normal control animals. Complex localization was evident in seven of ten nephrotoxic animals suggesting that the presence of immune mediated glomerular injury makes the kidney susceptibility to further immune injury.", "contents": "Glomerular localization of preformed immune complexes in nephrotoxic serum nephritis. Pre-formed immune complexes solubilized in antigen excess were infused into rats with nephrotoxic serum nephritis and normal control animals. Complex localization was evident in seven of ten nephrotoxic animals suggesting that the presence of immune mediated glomerular injury makes the kidney susceptibility to further immune injury."} {"id": "PMID:159540", "title": "Teratogenetic periods for the principal malformations of the central nervous system.", "content": "The teratogenetic periods of the most important CNS malformations are defined and briefly discussed. The results are presented in a synoptic figure. The present study is based on the analysis of normal CNS development and on morphogenetic interpretations of the pertinent anomalies. The data compiled from the literature concerning normal development are presented in an analytical table and are also summarized in a synoptic figure.", "contents": "Teratogenetic periods for the principal malformations of the central nervous system. The teratogenetic periods of the most important CNS malformations are defined and briefly discussed. The results are presented in a synoptic figure. The present study is based on the analysis of normal CNS development and on morphogenetic interpretations of the pertinent anomalies. The data compiled from the literature concerning normal development are presented in an analytical table and are also summarized in a synoptic figure."} {"id": "PMID:159542", "title": "Effects of plasma and serum on arterial endothelium.", "content": "Electron microscopic study of the femoral artery of rats following a single brief intra-arterial infusion of two different types of rat plasma and of rat serum led to the following findings and conclusions: 1. Plasma from heparinised blood caused no endothelial injury whatsoever whereas plasma from citrated blood damaged the arterial endothelium. Since the intra-arterial infusion of citrate alone produced an endothelial injury that was similar to that induced by plasma from citrated blood, it is very likely that the endothelium-injuring effect of the latter was due to its citrate content. 2. Serum obtained from clotted blood injured both the endothelium and some myocytes of the arteries into which it was infused. This injury was possibly due to the proteolytic or other actions of activated clotting factors, which are known to be present in serum but absent from plasma. The implications of these findings for certain areas of experimental and human pathology are discussed.", "contents": "Effects of plasma and serum on arterial endothelium. Electron microscopic study of the femoral artery of rats following a single brief intra-arterial infusion of two different types of rat plasma and of rat serum led to the following findings and conclusions: 1. Plasma from heparinised blood caused no endothelial injury whatsoever whereas plasma from citrated blood damaged the arterial endothelium. Since the intra-arterial infusion of citrate alone produced an endothelial injury that was similar to that induced by plasma from citrated blood, it is very likely that the endothelium-injuring effect of the latter was due to its citrate content. 2. Serum obtained from clotted blood injured both the endothelium and some myocytes of the arteries into which it was infused. This injury was possibly due to the proteolytic or other actions of activated clotting factors, which are known to be present in serum but absent from plasma. The implications of these findings for certain areas of experimental and human pathology are discussed."} {"id": "PMID:159543", "title": "Light and electron microscopic findings in five cases of cryoglobulinemic glomerulonephritis.", "content": "Renal tissue from five patients with cryoglobulinemia was studied by light and electron microscopy and immunofluorescence. None of the histologic features observed at the light microscopic level seems to be specific for cryoglobulinemia. Electron microscopic investigations have shown very large electron dense deposits in almost every examined lobule in all cases. The deposits displayed two main patterns; a homogeneous texture in two cases and tubular or annular structures in three cases. The patients with typically structured deposits had IgG-IgM cryoglobulinemia (2 cases) or monoclonal IgM cryoglobulinemia (1 case). The presence of IgM in cryoglobulinemia may be the cause of the peculiar structure of the deposits.", "contents": "Light and electron microscopic findings in five cases of cryoglobulinemic glomerulonephritis. Renal tissue from five patients with cryoglobulinemia was studied by light and electron microscopy and immunofluorescence. None of the histologic features observed at the light microscopic level seems to be specific for cryoglobulinemia. Electron microscopic investigations have shown very large electron dense deposits in almost every examined lobule in all cases. The deposits displayed two main patterns; a homogeneous texture in two cases and tubular or annular structures in three cases. The patients with typically structured deposits had IgG-IgM cryoglobulinemia (2 cases) or monoclonal IgM cryoglobulinemia (1 case). The presence of IgM in cryoglobulinemia may be the cause of the peculiar structure of the deposits."} {"id": "PMID:159544", "title": "Effects of dimethyl sulfoxide and colchicine on the resorption of experimental amyloid.", "content": "The induction of amyloid in C3H mice by either casein solution or complete Freund's adjuvant emulsion with Mycobacterium butyricum was confirmed by partial splenectomy. The animals were autopsied after treatment with dimethyl sulfoxide (550 mg/kg, 50 times), colchicine (0.02 mg/kg, 15--37 times), or saline solution as a control. Detailed histological comparisons of biopsy and autopsy spleens provided evidence that dimethyl sulfoxide was significantly effective in the resorption of amyloid, while in the animals treated with colchicine amyloid deposition was increased. The effect of dimethyl sulfoxide was discussed with reference to the modification of amyloid fibrils.", "contents": "Effects of dimethyl sulfoxide and colchicine on the resorption of experimental amyloid. The induction of amyloid in C3H mice by either casein solution or complete Freund's adjuvant emulsion with Mycobacterium butyricum was confirmed by partial splenectomy. The animals were autopsied after treatment with dimethyl sulfoxide (550 mg/kg, 50 times), colchicine (0.02 mg/kg, 15--37 times), or saline solution as a control. Detailed histological comparisons of biopsy and autopsy spleens provided evidence that dimethyl sulfoxide was significantly effective in the resorption of amyloid, while in the animals treated with colchicine amyloid deposition was increased. The effect of dimethyl sulfoxide was discussed with reference to the modification of amyloid fibrils."} {"id": "PMID:159545", "title": "Intercellular junctional specializations in human basal cell carcinoma. A freeze-fracture study.", "content": "Intercellular junctions of various types were found on the membrane fracture faces of human nodular basal cell carcinoma (BCC) cells. The junctional types represented include desmosomes, tight junctions, and gap junctions. A semiquantitative comparison of undifferentiated and differentiated nodular BCC showed that gap and tight junctions were observed on all exposed membrane fracture interfaces of the differentiated tumors, while only fifty six per cent of the membrane interfaces of the undifferentiated tumor exhibited similar junctional specializations. These membrane specializations may be a partial reflection of differentiation among the different types of BCC and their contribution to the less invasive character of nodular BCC cannot be ruled out.", "contents": "Intercellular junctional specializations in human basal cell carcinoma. A freeze-fracture study. Intercellular junctions of various types were found on the membrane fracture faces of human nodular basal cell carcinoma (BCC) cells. The junctional types represented include desmosomes, tight junctions, and gap junctions. A semiquantitative comparison of undifferentiated and differentiated nodular BCC showed that gap and tight junctions were observed on all exposed membrane fracture interfaces of the differentiated tumors, while only fifty six per cent of the membrane interfaces of the undifferentiated tumor exhibited similar junctional specializations. These membrane specializations may be a partial reflection of differentiation among the different types of BCC and their contribution to the less invasive character of nodular BCC cannot be ruled out."} {"id": "PMID:159548", "title": "Adrenal adenomata causing primary aldosteronism. An ultrastructural study of twenty five cases.", "content": "Adenomata taken from 25 patients with primary aldosteronism were observed by electron microscopy. The cells in the adenoma had a well developed agranular endoplasmic reticulum but granular endoplasmic reticulum was not prominent. Most of the mitochondria resembled those in the cells of the zona glomerulosa, suggesting that the adenomata which caused primary aldosteronism are derived from this zone. Spironolactone bodies were found in the cells of the adenoma from a patient who received spironolactone. Their appearance was identical to that described in previous reports.", "contents": "Adrenal adenomata causing primary aldosteronism. An ultrastructural study of twenty five cases. Adenomata taken from 25 patients with primary aldosteronism were observed by electron microscopy. The cells in the adenoma had a well developed agranular endoplasmic reticulum but granular endoplasmic reticulum was not prominent. Most of the mitochondria resembled those in the cells of the zona glomerulosa, suggesting that the adenomata which caused primary aldosteronism are derived from this zone. Spironolactone bodies were found in the cells of the adenoma from a patient who received spironolactone. Their appearance was identical to that described in previous reports."} {"id": "PMID:159552", "title": "Myxoid liposarcoma. An electronmicroscopic study: biological and histogenetic considerations.", "content": "Ten myxoid liposarcomas (ML) were studied ultrastructurally in an attempt to determine the histogenesis of this neoplasm and structural associations which might contribute to their relatively benign clinical behavior. The findings were compared with normal and neoplastic adipose tissue. Three cell types were observed, i.e., \"primitive\" mesenchymal cells, intermediate cell types, and lipoblasts at various stages of development. The principle differences between the lipoblastic elements were the number and the size of intracytoplasmic fat vacuoles, the development of basement membrane-like material, micropinocytotic vesicles along the plasma membrane and the quantity and pleomorphism of mitochondria. The tumor vasculature was complex but consistently demonstrated a multilayered basal lamina. This finding has been described in neoplasms associated with a relatively good prognosis. This study demonstrates that the better differentiated lipoblasts in ML share some features with normal brown fetal fat and hibernoma. It is, thus, suggested that ML may be derived from brown adipose tissue.", "contents": "Myxoid liposarcoma. An electronmicroscopic study: biological and histogenetic considerations. Ten myxoid liposarcomas (ML) were studied ultrastructurally in an attempt to determine the histogenesis of this neoplasm and structural associations which might contribute to their relatively benign clinical behavior. The findings were compared with normal and neoplastic adipose tissue. Three cell types were observed, i.e., \"primitive\" mesenchymal cells, intermediate cell types, and lipoblasts at various stages of development. The principle differences between the lipoblastic elements were the number and the size of intracytoplasmic fat vacuoles, the development of basement membrane-like material, micropinocytotic vesicles along the plasma membrane and the quantity and pleomorphism of mitochondria. The tumor vasculature was complex but consistently demonstrated a multilayered basal lamina. This finding has been described in neoplasms associated with a relatively good prognosis. This study demonstrates that the better differentiated lipoblasts in ML share some features with normal brown fetal fat and hibernoma. It is, thus, suggested that ML may be derived from brown adipose tissue."} {"id": "PMID:159553", "title": "Cartilaginous metaplasia and overgrowth of neurocranium skull after X-irradiation in utero.", "content": "Prenatal X-irradiation of mice in the late organogenesis stage either with a fractionated or a single exposure dose (3 X 160 R or 200 R) leads to remarkable, previously undescribed malformations of the skull. These malformations range from mild hyperostotic nodule formation in about 90% of the offspring to excessive formation of desmal bony tissues, which extend deep into the forebrain and are thus only detectable in histological sections. Metaplastic and hyperplastic formation of cartilage in all the neurocranial regions is observed in about 10% of the offspring. The pathogenesis of these overgrowth phenomena is presumably related to a growth disturbance of both the mesenchymal skull primordium and the brain. While malformation of the latter leads to a decrease of intracranial pressure and consequently to altered growth activity of the skull sutures, the reparative and proliferative capacities of the mesenchyme are also stimulated, in a hyperplastic direction, by X-irradiation.", "contents": "Cartilaginous metaplasia and overgrowth of neurocranium skull after X-irradiation in utero. Prenatal X-irradiation of mice in the late organogenesis stage either with a fractionated or a single exposure dose (3 X 160 R or 200 R) leads to remarkable, previously undescribed malformations of the skull. These malformations range from mild hyperostotic nodule formation in about 90% of the offspring to excessive formation of desmal bony tissues, which extend deep into the forebrain and are thus only detectable in histological sections. Metaplastic and hyperplastic formation of cartilage in all the neurocranial regions is observed in about 10% of the offspring. The pathogenesis of these overgrowth phenomena is presumably related to a growth disturbance of both the mesenchymal skull primordium and the brain. While malformation of the latter leads to a decrease of intracranial pressure and consequently to altered growth activity of the skull sutures, the reparative and proliferative capacities of the mesenchyme are also stimulated, in a hyperplastic direction, by X-irradiation."} {"id": "PMID:159554", "title": "Ovarian sex cord tumor with annular tubules. Clinicopathologic report of two benign and one malignant cases with long follow-ups.", "content": "The clinicopathologic features of three new cases of ovarian sex cord tumors with annular tubules are presented, thereby increasing to 23 the number of the published cases in the world literature. These three observations, along with another one which was previously published, were found in the files of the Institute of Pathology of the University of Lausanne from 1939 to 1978. Forty-seven granulosa cell tumors and eight Sertoli and/or Leydig cell tumors of the ovary were found during the same 40-year period. The patients were 48, 64 and 71 years of age. No sign of the Peutz-Jeghers syndrome was noticed in the three patients. All three tumors caused metrorrhagias as a cardinal sign. They were bulky, unilateral and were formed by solid tissue with cystic spaces. Histologically, the most characteristic pattern consisted of simple and complex tubular structures as described by Scully in 1970. Two patients, in which the mitotic indexes of the tumors were lower than 5 mitoses per 10 HPF, died without evidence of a recurrence 36 and 37 years after surgical ablation of the tumor. The third patient, whose neoplasm featured fewer well differentiated tubular structures than the two previous ones and had a mitotic index of over 70 mitoses per 10 HPF, died from massive abdominal recurrence after 5 years and 5 months.", "contents": "Ovarian sex cord tumor with annular tubules. Clinicopathologic report of two benign and one malignant cases with long follow-ups. The clinicopathologic features of three new cases of ovarian sex cord tumors with annular tubules are presented, thereby increasing to 23 the number of the published cases in the world literature. These three observations, along with another one which was previously published, were found in the files of the Institute of Pathology of the University of Lausanne from 1939 to 1978. Forty-seven granulosa cell tumors and eight Sertoli and/or Leydig cell tumors of the ovary were found during the same 40-year period. The patients were 48, 64 and 71 years of age. No sign of the Peutz-Jeghers syndrome was noticed in the three patients. All three tumors caused metrorrhagias as a cardinal sign. They were bulky, unilateral and were formed by solid tissue with cystic spaces. Histologically, the most characteristic pattern consisted of simple and complex tubular structures as described by Scully in 1970. Two patients, in which the mitotic indexes of the tumors were lower than 5 mitoses per 10 HPF, died without evidence of a recurrence 36 and 37 years after surgical ablation of the tumor. The third patient, whose neoplasm featured fewer well differentiated tubular structures than the two previous ones and had a mitotic index of over 70 mitoses per 10 HPF, died from massive abdominal recurrence after 5 years and 5 months."} {"id": "PMID:159555", "title": "Morphological alterations of rabbit oviducts following ligature of the tubal isthmus.", "content": "An animal model of tubal sterilisation would be valuable in order to examine the problem of severe damage of the tubal wall and to study the criteria for optimal anastomosis. In a preliminary experimental group the Fallopian tubes of 30 rabbits were ligated at the isthmic segment. Specimens of the ligated portion and other tubal segments have been investigated by light microscopy and scanning and transmission electronmicroscopy one, four and twelve weeks following the ligature. Changes in the Fallopian tubes following the ligature were limited to the ligated portion. The morphological findings consisted of a flattening and decrease of differentiation of the mucous epithelium, and of a slight scarring in the tubal wall and in the subperitoneal tissue within the constricted segment. Tubal ligation at the isthmic segment provides good conditions for refertilisation, following resection of the altered portion and microsurgical anastomosis.", "contents": "Morphological alterations of rabbit oviducts following ligature of the tubal isthmus. An animal model of tubal sterilisation would be valuable in order to examine the problem of severe damage of the tubal wall and to study the criteria for optimal anastomosis. In a preliminary experimental group the Fallopian tubes of 30 rabbits were ligated at the isthmic segment. Specimens of the ligated portion and other tubal segments have been investigated by light microscopy and scanning and transmission electronmicroscopy one, four and twelve weeks following the ligature. Changes in the Fallopian tubes following the ligature were limited to the ligated portion. The morphological findings consisted of a flattening and decrease of differentiation of the mucous epithelium, and of a slight scarring in the tubal wall and in the subperitoneal tissue within the constricted segment. Tubal ligation at the isthmic segment provides good conditions for refertilisation, following resection of the altered portion and microsurgical anastomosis."} {"id": "PMID:159556", "title": "[On the development of the skin of the digital pulp in the early fetal period (author's transl)].", "content": "The skin of the digital pulp is of pathologic as well as of forensic interest. Investigations were made with the scanning electron microscope on the fingers of 27 fetuses to get a new insight into the development of this part of the skin. The formation of the peridermal cells is already striking in this region in the early fetal period. A certain grouping together of these peridermal cells appears to resemble the later developed epidermal ridge. The dermatoglyphics are fully developed by the end of the second trimenon. A more exact time sequence cannot be established due to fluxional transitions and, particularly, to marked individual veriations.", "contents": "[On the development of the skin of the digital pulp in the early fetal period (author's transl)]. The skin of the digital pulp is of pathologic as well as of forensic interest. Investigations were made with the scanning electron microscope on the fingers of 27 fetuses to get a new insight into the development of this part of the skin. The formation of the peridermal cells is already striking in this region in the early fetal period. A certain grouping together of these peridermal cells appears to resemble the later developed epidermal ridge. The dermatoglyphics are fully developed by the end of the second trimenon. A more exact time sequence cannot be established due to fluxional transitions and, particularly, to marked individual veriations."} {"id": "PMID:159565", "title": "[Kyzylagach virus (family Togaviridae, genus alphaviruses), a new arbovirus isolated from Culex modestus mosquitoes trapped in the Azerbaijani SSR].", "content": "A strain of LEIV 65A virus was isolated in 1969 from Culex modestus mosquitoes collected in the Kyzylagach preserve, the Azerbaijan SSR, in a colony of Ciconiiformes birds. Investigations of the antigenic properties of this virus by the complement fixation and neutralization tests as well as by electron microscopy showed it to belong to alphaviruses of the Togaviridae family. Kyzylagach virus had one-way relations with Sindbis virus. Some biological and biophysical-biochemical properties of the virus were studied.", "contents": "[Kyzylagach virus (family Togaviridae, genus alphaviruses), a new arbovirus isolated from Culex modestus mosquitoes trapped in the Azerbaijani SSR]. A strain of LEIV 65A virus was isolated in 1969 from Culex modestus mosquitoes collected in the Kyzylagach preserve, the Azerbaijan SSR, in a colony of Ciconiiformes birds. Investigations of the antigenic properties of this virus by the complement fixation and neutralization tests as well as by electron microscopy showed it to belong to alphaviruses of the Togaviridae family. Kyzylagach virus had one-way relations with Sindbis virus. Some biological and biophysical-biochemical properties of the virus were studied."} {"id": "PMID:159590", "title": "[Staphylococcus aureus in poultry--biochemical characteristics, antibiotic resistance and phage pattern (author's transl)].", "content": "In a poultry processing plant in northern Germany 1412 swabs were taken from poultry carcasses together with 608 swabs from the personnel. The broilers came from 22 different chicken farms. The swabs taken from the poultry and those taken from the personnel proved to be 35% and 48% Staph. aureus positive respectively. The swabs taken from the feathers and from the skin were staphylococcal positive at a higher level (47%) than the swabs taken from the cloaca (19%) and the throat (23%). Between 8% and 63% of the animals from the various chicken farms were Staph. aureus positive. The frequency of staphylococcal contamination increased during the course of slaughter. 57% of the swabs taken from the gloves and the hands and 42% from the aprons of the personnel were Staph. aureus positive. Some biochemical properties, the phage patterns, and the antibiotic resistance against oleandomycin, erythromycin, bacitracin, streptomycin, tetracyclin, penicillin, chloramphenicol, virginiamycin and flavomycin were determined from 445 poultry and 345 personnel Staph. aureus isolates. Only small differences could be established between both sources in this way. Only 20% of the personnel and 34% of the chicken strains were resistant to antibiotics. In the strains collected from personnel, penicillin-resistance predominated while the poultry isolates showed predominantly tetracyclin-resistance. Of all antibiotics applied nutritively in the chicken fattening, there was a higher resistance only against oleandomycin (11% of the poultry strains). Between the chicken farms there was a different frequency of resistance (0--68%). The source of the staphylococci could be determined for only some of the strains. Only 2.5% of the chicken isolates showed characteristics described in the literature to be \"poultry-specific\", whereas 37% of the personnel and 24% of the poultry isolates were shown to be \"human-specific\" strains. It seems that the vast majority of the staphylococci originated from the slaughterhouse personnel. The rest of the strains differed in varying combinations of their properties from the given species characteristics. Although Staph. aureus was brought into the slaughterhouse by the poultry, the contaminations of the final product seemed to originate mainly from human beings.", "contents": "[Staphylococcus aureus in poultry--biochemical characteristics, antibiotic resistance and phage pattern (author's transl)]. In a poultry processing plant in northern Germany 1412 swabs were taken from poultry carcasses together with 608 swabs from the personnel. The broilers came from 22 different chicken farms. The swabs taken from the poultry and those taken from the personnel proved to be 35% and 48% Staph. aureus positive respectively. The swabs taken from the feathers and from the skin were staphylococcal positive at a higher level (47%) than the swabs taken from the cloaca (19%) and the throat (23%). Between 8% and 63% of the animals from the various chicken farms were Staph. aureus positive. The frequency of staphylococcal contamination increased during the course of slaughter. 57% of the swabs taken from the gloves and the hands and 42% from the aprons of the personnel were Staph. aureus positive. Some biochemical properties, the phage patterns, and the antibiotic resistance against oleandomycin, erythromycin, bacitracin, streptomycin, tetracyclin, penicillin, chloramphenicol, virginiamycin and flavomycin were determined from 445 poultry and 345 personnel Staph. aureus isolates. Only small differences could be established between both sources in this way. Only 20% of the personnel and 34% of the chicken strains were resistant to antibiotics. In the strains collected from personnel, penicillin-resistance predominated while the poultry isolates showed predominantly tetracyclin-resistance. Of all antibiotics applied nutritively in the chicken fattening, there was a higher resistance only against oleandomycin (11% of the poultry strains). Between the chicken farms there was a different frequency of resistance (0--68%). The source of the staphylococci could be determined for only some of the strains. Only 2.5% of the chicken isolates showed characteristics described in the literature to be \"poultry-specific\", whereas 37% of the personnel and 24% of the poultry isolates were shown to be \"human-specific\" strains. It seems that the vast majority of the staphylococci originated from the slaughterhouse personnel. The rest of the strains differed in varying combinations of their properties from the given species characteristics. Although Staph. aureus was brought into the slaughterhouse by the poultry, the contaminations of the final product seemed to originate mainly from human beings."} {"id": "PMID:159595", "title": "[Immunological structure of the population vis-\u00e0-vis the meningococcus].", "content": "The immunological and epidemiological study of 3362 serum samples selectively taken from healthy persons in Yaroslavl showed the presence of highly pronounced inverse correlation between morbidity rate indices and level of antibodies, as well as direct correlation between the level of carriership and the level of antibodies, which indicated the specific character of this process. The analysis of serological data showed that all meningococcal antigenic fractions took part in the formation of the immunological structure of the population, but lipopolysaccharides and polysaccharides played the most active role in this process. The level of all immunoglobulin classes (especially IgA) in the sera of the persons selected for this study was also shown to depend on their age.", "contents": "[Immunological structure of the population vis-\u00e0-vis the meningococcus]. The immunological and epidemiological study of 3362 serum samples selectively taken from healthy persons in Yaroslavl showed the presence of highly pronounced inverse correlation between morbidity rate indices and level of antibodies, as well as direct correlation between the level of carriership and the level of antibodies, which indicated the specific character of this process. The analysis of serological data showed that all meningococcal antigenic fractions took part in the formation of the immunological structure of the population, but lipopolysaccharides and polysaccharides played the most active role in this process. The level of all immunoglobulin classes (especially IgA) in the sera of the persons selected for this study was also shown to depend on their age."} {"id": "PMID:159596", "title": "[Effectiveness of social hygiene and organized preventive measures in dysentery in preschool institutions].", "content": "The work presents the data on the development and realization of the complex of social and hygienic, as well as organizational and preventive measures for dysentery control at institutions for children of preschool age in one of the regions of our country. This complex comprises the improvement of \"epidemiological\" knowledge of the staff, preventive orientation in the work of the epidemiological section of the local Sanitary Epidemiological Station, the spread of sanitary and hygienic knowledge children and in their families, the improvement of material and technical equipment of children's institutions. The complex proved to be highly effective: at institutions for children of preschool age morbidity -ate in dysentery decrease 4--5 times, and its specific falue dropped from 40% to 5.4%, the frequency of positive results given by tests for the presence of intestinal microflora in washings from various objects decreased more than 25 times. Morbidity rate at institutions for children of preschool age decreased 4--5 times as compared with that among children not attending such institutions. The above data suggest the necessity of introducing this experience in other regions of our country.", "contents": "[Effectiveness of social hygiene and organized preventive measures in dysentery in preschool institutions]. The work presents the data on the development and realization of the complex of social and hygienic, as well as organizational and preventive measures for dysentery control at institutions for children of preschool age in one of the regions of our country. This complex comprises the improvement of \"epidemiological\" knowledge of the staff, preventive orientation in the work of the epidemiological section of the local Sanitary Epidemiological Station, the spread of sanitary and hygienic knowledge children and in their families, the improvement of material and technical equipment of children's institutions. The complex proved to be highly effective: at institutions for children of preschool age morbidity -ate in dysentery decrease 4--5 times, and its specific falue dropped from 40% to 5.4%, the frequency of positive results given by tests for the presence of intestinal microflora in washings from various objects decreased more than 25 times. Morbidity rate at institutions for children of preschool age decreased 4--5 times as compared with that among children not attending such institutions. The above data suggest the necessity of introducing this experience in other regions of our country."} {"id": "PMID:159593", "title": "[Evolution of mechanisms regulating the reaction between actin and myosin].", "content": "In the paper we consider some aspects of evolution of actin, myosin, and Ca2+-binding proteins regulating their interaction. On the basis of the data recently obtained, we propose the following theses: 1. All types of motility in the living world where actin and myosin are involved, are based on active sliding of actin filaments along myosin filaments (or less organized myosin aggregates). 2. Ca2+-sensitivity of actin-myosin interaction is as old as actin and myosin themselves. Therefore, Ca2+-independent actomyosin ATPase found in vitro does not correspond to physiological sutuation and in this sense relfects an experimental artefact. 3. All proteins which regulate Ca2+-sensitivity of actin and myosin interaction, contain EF-hand structure. 4. It is generally believed that non-muscle cells, including Protozoa and Myxomycetes, contain all regulatory mechanisms which were described for muscles. However, in our opinion, troponin complex similar to that found in striated muscles, if present does not operate there.", "contents": "[Evolution of mechanisms regulating the reaction between actin and myosin]. In the paper we consider some aspects of evolution of actin, myosin, and Ca2+-binding proteins regulating their interaction. On the basis of the data recently obtained, we propose the following theses: 1. All types of motility in the living world where actin and myosin are involved, are based on active sliding of actin filaments along myosin filaments (or less organized myosin aggregates). 2. Ca2+-sensitivity of actin-myosin interaction is as old as actin and myosin themselves. Therefore, Ca2+-independent actomyosin ATPase found in vitro does not correspond to physiological sutuation and in this sense relfects an experimental artefact. 3. All proteins which regulate Ca2+-sensitivity of actin and myosin interaction, contain EF-hand structure. 4. It is generally believed that non-muscle cells, including Protozoa and Myxomycetes, contain all regulatory mechanisms which were described for muscles. However, in our opinion, troponin complex similar to that found in striated muscles, if present does not operate there."} {"id": "PMID:159594", "title": "[Ultrastructural organization of the inner medullary zone of the kidney of the water vole Arvicola terrestris].", "content": "Papillary component ultrastructure and acid mucopolysaccharide distribution have been investigated in the kidney of the water vole A. terrestris. Structural differences between the descending and ascending parts of the Henle's loop are rather small, cell cytoplasm of these segments being poor in organells. Unusual ultrastructure of the collecting duct epithelium with high level of cytoplasmic organization (elongated thin mitochondria, fairly developed Golgi complex, numerous phagosomes and pinocytotic vesicles, long branching microvilli) was described. Apical membrane of the epithelium is covered by rich glycocalix layer. Heil-positive substrances are located intracellularly inside phagosomes and on vesicle membranes, as well as on the membranes of cisternae of endoplasmic reticulum. Interstitium is abundant, but no close contacts between papillary components were found. Acid mucopolysaccharide content of the interstitium is low, \"gel\" filter being not formed. The described peculiarities are discussed in relation to water and salt metabolism of the rodents investigated.", "contents": "[Ultrastructural organization of the inner medullary zone of the kidney of the water vole Arvicola terrestris]. Papillary component ultrastructure and acid mucopolysaccharide distribution have been investigated in the kidney of the water vole A. terrestris. Structural differences between the descending and ascending parts of the Henle's loop are rather small, cell cytoplasm of these segments being poor in organells. Unusual ultrastructure of the collecting duct epithelium with high level of cytoplasmic organization (elongated thin mitochondria, fairly developed Golgi complex, numerous phagosomes and pinocytotic vesicles, long branching microvilli) was described. Apical membrane of the epithelium is covered by rich glycocalix layer. Heil-positive substrances are located intracellularly inside phagosomes and on vesicle membranes, as well as on the membranes of cisternae of endoplasmic reticulum. Interstitium is abundant, but no close contacts between papillary components were found. Acid mucopolysaccharide content of the interstitium is low, \"gel\" filter being not formed. The described peculiarities are discussed in relation to water and salt metabolism of the rodents investigated."} {"id": "PMID:159598", "title": "Temperature compensation of sodium transport and ATPase activity in frog skin.", "content": "Na+ transport across frog skin, measured as short-circuit current (SCC) shows perfect temperature compensation in frogs acclimated to 6 degrees, 12 degrees, and 23 degrees C as SCC values observed at the acclimation temperatures are equal (about 13 muA/cm2). Reacclimation experiments show that this is not a starvation effect. While very little temperature compensation is seen in the activity of Na+, K+-ATPase in epidermal homogenates from frog skins, the activity of Mg2+-ATPase shows inverse compensation at assay temperatures from 4 degrees to 48 degrees C. This ATPase is apparently activated either by Mg2+ or by Ca2+ and it probably controls the passive permeability of epidermal cells. It is suggested that the inverse temperature compensation in the activity of this enzyme is the main mechanism by which the observed perfect temperature compensation of Na+ transport across frog skin occurs.", "contents": "Temperature compensation of sodium transport and ATPase activity in frog skin. Na+ transport across frog skin, measured as short-circuit current (SCC) shows perfect temperature compensation in frogs acclimated to 6 degrees, 12 degrees, and 23 degrees C as SCC values observed at the acclimation temperatures are equal (about 13 muA/cm2). Reacclimation experiments show that this is not a starvation effect. While very little temperature compensation is seen in the activity of Na+, K+-ATPase in epidermal homogenates from frog skins, the activity of Mg2+-ATPase shows inverse compensation at assay temperatures from 4 degrees to 48 degrees C. This ATPase is apparently activated either by Mg2+ or by Ca2+ and it probably controls the passive permeability of epidermal cells. It is suggested that the inverse temperature compensation in the activity of this enzyme is the main mechanism by which the observed perfect temperature compensation of Na+ transport across frog skin occurs."} {"id": "PMID:159599", "title": "The effect of surgical sympathectomy and of neonatal treatment with 6-hydroxydopamine and guanethidine on particle-bound noradrenaline and 35S-sulphomucopolysaccharides.", "content": "Five to six weeks after bilateral stellate ganglionectomy, noradrenaline (NA) levels in cats' atria were reduced to approximately 20% of controls. In vivo uptake of 3H-NA and of 35S-sulphate into gradient fractions containing noradrenergic vesicles from the atria decreased to approximately 30% and approximately 40%, respectively. The uptakes of 3H-NA and 35S-sulphate were significantly correlated in both control and ganglionectomized cats, and the distributions of 3H and 35S on the gradients were parallel. The findings suggest that sulphomucopolysaccharides (SMPSs) may be localized in noradrenergic vesicles, possibly participating in the storage of Na. in 10-week-old rats treated neonatally with either 6-hydroxydopamine (6-OH-DA) or guanethidine, levels of NA in the heart, spleen and salivary glands were decreased to less than 10% and to 10-20%, respectively; in the seminal ducts to 33% and 45%, respectively. 3H-NA uptake into noradrenergic-vesicle-enriched subcellular fractions from the heart, spleen and salivary glands of 6-OH-DA treated rats decreased almost to the extent of NA depletion but in the seminal ducts the decrease was less marked. Guanethidine treatment left the uptake unaffected, except for the spleen. The discrepancy between storage and uptake suggests that surviving neurons display during their outgrowth into tissues a high uptake capacity but lack full NA synthesis. 35S-sulphate incorporation into non-lipid compounds, presumably SMPSs, in the noradrenergic-vesicle-enriched fractions appeared unaffected or increased over corresponding control levels, possibly due to high synthetic activity in the growing neurons.", "contents": "The effect of surgical sympathectomy and of neonatal treatment with 6-hydroxydopamine and guanethidine on particle-bound noradrenaline and 35S-sulphomucopolysaccharides. Five to six weeks after bilateral stellate ganglionectomy, noradrenaline (NA) levels in cats' atria were reduced to approximately 20% of controls. In vivo uptake of 3H-NA and of 35S-sulphate into gradient fractions containing noradrenergic vesicles from the atria decreased to approximately 30% and approximately 40%, respectively. The uptakes of 3H-NA and 35S-sulphate were significantly correlated in both control and ganglionectomized cats, and the distributions of 3H and 35S on the gradients were parallel. The findings suggest that sulphomucopolysaccharides (SMPSs) may be localized in noradrenergic vesicles, possibly participating in the storage of Na. in 10-week-old rats treated neonatally with either 6-hydroxydopamine (6-OH-DA) or guanethidine, levels of NA in the heart, spleen and salivary glands were decreased to less than 10% and to 10-20%, respectively; in the seminal ducts to 33% and 45%, respectively. 3H-NA uptake into noradrenergic-vesicle-enriched subcellular fractions from the heart, spleen and salivary glands of 6-OH-DA treated rats decreased almost to the extent of NA depletion but in the seminal ducts the decrease was less marked. Guanethidine treatment left the uptake unaffected, except for the spleen. The discrepancy between storage and uptake suggests that surviving neurons display during their outgrowth into tissues a high uptake capacity but lack full NA synthesis. 35S-sulphate incorporation into non-lipid compounds, presumably SMPSs, in the noradrenergic-vesicle-enriched fractions appeared unaffected or increased over corresponding control levels, possibly due to high synthetic activity in the growing neurons."} {"id": "PMID:159600", "title": "Cardiovascular 'reactivity' to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats.", "content": "Cardiovascular 'reactivity' to graded splanchnic nerve stimulation was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/ri of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle.", "contents": "Cardiovascular 'reactivity' to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats. Cardiovascular 'reactivity' to graded splanchnic nerve stimulation was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/ri of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle."} {"id": "PMID:159601", "title": "Prognosis in hypertrophic obstructive cardiomyopathy.", "content": "Thirty-eight non-operated patients with hypertrophic obstructive cardiomyopathy (HOCM) were followed for 1--18 years (mean 8). Twelve patients died, nine of them instantaneously without any other apparent cause of death. The symptoms on the first admission did not discriminate between those who died and those who survived during the observation period, nor did the findings at heart catheterization at rest or left ventricular angiocardiography. However, cardiac enlargement on the first chest X-ray was significantly more common in the decreased group, 75% against 27%, as was the complete absence of a q-wave in lead III on the first ECG, 83% against 42%. The combination of complete lack of q in lead III and cardiac enlargement on chest X-ray at the initial examination was present in 9 of the 12 deceased (75%) and in only 3 of 24 survivors (13%). This can be used to select patients for long-term prophylaxis against ventricular fibrillation which, according to the literature, is the main mechanism of instantaneous death in HOCM.", "contents": "Prognosis in hypertrophic obstructive cardiomyopathy. Thirty-eight non-operated patients with hypertrophic obstructive cardiomyopathy (HOCM) were followed for 1--18 years (mean 8). Twelve patients died, nine of them instantaneously without any other apparent cause of death. The symptoms on the first admission did not discriminate between those who died and those who survived during the observation period, nor did the findings at heart catheterization at rest or left ventricular angiocardiography. However, cardiac enlargement on the first chest X-ray was significantly more common in the decreased group, 75% against 27%, as was the complete absence of a q-wave in lead III on the first ECG, 83% against 42%. The combination of complete lack of q in lead III and cardiac enlargement on chest X-ray at the initial examination was present in 9 of the 12 deceased (75%) and in only 3 of 24 survivors (13%). This can be used to select patients for long-term prophylaxis against ventricular fibrillation which, according to the literature, is the main mechanism of instantaneous death in HOCM."} {"id": "PMID:159605", "title": "[Development tendencies of the contact allergy].", "content": "The development tendencies of the contact allergy in the given catch-area in the years 1948-1977 are studied here by the help of a systematic examination of the dynamics concerning the hypersensitivity of the population. By means of patch tests applied to 15685 patients/6864 men and 8821 women/reactors are checked up towards 15 contact allergens/hexavalent and trivalent chromium, nickel, cobalt, procaine, paraphenylenediamine, neomycine, mercury bichloride, resorcinol, camomile, paraben mixture, formaldehyde, balsam of Peru, turpentine oil, rubber chemicals, and the connections between the percentage of the reactors and the alterations in the technology of the production as well as of the degree and effektiveness of the preventive measures and of the introduction of new remedies, cosmetics and necessaries for daily use are being determined. At the same time this study and the results achieved by analysis are the basis for preventive measures to be taken according to the characteristics of the contact allergens and in proportion to the possibility of taking such measures.", "contents": "[Development tendencies of the contact allergy]. The development tendencies of the contact allergy in the given catch-area in the years 1948-1977 are studied here by the help of a systematic examination of the dynamics concerning the hypersensitivity of the population. By means of patch tests applied to 15685 patients/6864 men and 8821 women/reactors are checked up towards 15 contact allergens/hexavalent and trivalent chromium, nickel, cobalt, procaine, paraphenylenediamine, neomycine, mercury bichloride, resorcinol, camomile, paraben mixture, formaldehyde, balsam of Peru, turpentine oil, rubber chemicals, and the connections between the percentage of the reactors and the alterations in the technology of the production as well as of the degree and effektiveness of the preventive measures and of the introduction of new remedies, cosmetics and necessaries for daily use are being determined. At the same time this study and the results achieved by analysis are the basis for preventive measures to be taken according to the characteristics of the contact allergens and in proportion to the possibility of taking such measures."} {"id": "PMID:159606", "title": "[The Langerhans cell--its macrophages-analogous function in the triggering of the allergic contact eczema (author's transl)].", "content": "1. Langerhans cells represent specific granula-containing dendritic cells which do not have desmosomes, tonofilaments and (pre)melanosomes and which therefore appear as clear cells in the epithelial tissue. 2. They occur in the squamous epithelium, and also in the corium, lymph node and thymus. They account for 1-1,7% of the whole volumen of the epidermis. 3. They do not represent effete melanocytes, but they originate from the mesenchym. Their migration from the dermis into the epidermis, their identity with histiocytosis X cells, their surface receptors as well as function underline the mesenchymal origin. 4. Probably the Langerhans cells regulate the mitosis and differentiation of the keratinocytes. 5. The antigen-presenting and lymphocyte stimulating functions of Langerhans cells as effector cells in allergic contact eczema are proved. They are able to phagocytize antigens (haptens), to apposite lymphozytes, to proliferate after the challenge by antigens as well as to migrate through the lymph vessels into the regional lymph nodes. 6. At their surface they bear receptors for Fc-IgG and C3 as well as Ia-antigens as immune response genes of the major histocompatibility complex (MHC). 7. With regard to point 5 and 6 they have the same properties as the macrophages. 8. Langerhans cells are damaged and destroyed, respectively, by immune complexes after activation of the complement pathway as well as by killer T-lymphocytes. Thus they are regulated as target cells by humoral and cellular mechanisms. 9. The allergic inflammatory reaction is triggered by mediator substances (of lysosomal origin?) which are liberated by the destruction of the Langerhans cells as well as by lymphokines. The preferently suprabasal occurrence of the Langerhans cells explains the early beginning of the edema and spongiosis as well as their localization in the lower layers of the epidermis. 10. The macrophages-analogous and antigen-presenting functions, which are genetically regulated are essential for the sensitization in allergic contact eczema. The ability to stimulate allogenic T-Lymphocytes in the mixed lymphocyte reaction might be of particular importance for the skin transplantation.", "contents": "[The Langerhans cell--its macrophages-analogous function in the triggering of the allergic contact eczema (author's transl)]. 1. Langerhans cells represent specific granula-containing dendritic cells which do not have desmosomes, tonofilaments and (pre)melanosomes and which therefore appear as clear cells in the epithelial tissue. 2. They occur in the squamous epithelium, and also in the corium, lymph node and thymus. They account for 1-1,7% of the whole volumen of the epidermis. 3. They do not represent effete melanocytes, but they originate from the mesenchym. Their migration from the dermis into the epidermis, their identity with histiocytosis X cells, their surface receptors as well as function underline the mesenchymal origin. 4. Probably the Langerhans cells regulate the mitosis and differentiation of the keratinocytes. 5. The antigen-presenting and lymphocyte stimulating functions of Langerhans cells as effector cells in allergic contact eczema are proved. They are able to phagocytize antigens (haptens), to apposite lymphozytes, to proliferate after the challenge by antigens as well as to migrate through the lymph vessels into the regional lymph nodes. 6. At their surface they bear receptors for Fc-IgG and C3 as well as Ia-antigens as immune response genes of the major histocompatibility complex (MHC). 7. With regard to point 5 and 6 they have the same properties as the macrophages. 8. Langerhans cells are damaged and destroyed, respectively, by immune complexes after activation of the complement pathway as well as by killer T-lymphocytes. Thus they are regulated as target cells by humoral and cellular mechanisms. 9. The allergic inflammatory reaction is triggered by mediator substances (of lysosomal origin?) which are liberated by the destruction of the Langerhans cells as well as by lymphokines. The preferently suprabasal occurrence of the Langerhans cells explains the early beginning of the edema and spongiosis as well as their localization in the lower layers of the epidermis. 10. The macrophages-analogous and antigen-presenting functions, which are genetically regulated are essential for the sensitization in allergic contact eczema. The ability to stimulate allogenic T-Lymphocytes in the mixed lymphocyte reaction might be of particular importance for the skin transplantation."} {"id": "PMID:159607", "title": "Antigammaglobulin antibodies in experimental adjuvant arthritis.", "content": "Several-fold administration of complete Freund's adjuvant in rat provoked acute arthritis accompanied by production of antigammaglobulin antibodies in a high percentage from the animals studied; their sera precipitate homologous and heterologous aggregated IgG and demonstrate hemagglutination titers up to 1 : 1792. To confirm the Ig type of the studied antibodies, rat sera were fractionated by gel filtration on Sephadex G200 by pH = 4.0 and by preparative ultra-centrifugation by pH = 3.6. It was established that the antibodies are of IgM type. - The presence of autoantibodies in an autoimmune disease, such as experimental adjuvant arthritis similar to the rheumatoid factors in human rheumatoid arthritis gives support to the statement that autoimmune processes are involved in the etiology of rheumatoid arthritis in men.", "contents": "Antigammaglobulin antibodies in experimental adjuvant arthritis. Several-fold administration of complete Freund's adjuvant in rat provoked acute arthritis accompanied by production of antigammaglobulin antibodies in a high percentage from the animals studied; their sera precipitate homologous and heterologous aggregated IgG and demonstrate hemagglutination titers up to 1 : 1792. To confirm the Ig type of the studied antibodies, rat sera were fractionated by gel filtration on Sephadex G200 by pH = 4.0 and by preparative ultra-centrifugation by pH = 3.6. It was established that the antibodies are of IgM type. - The presence of autoantibodies in an autoimmune disease, such as experimental adjuvant arthritis similar to the rheumatoid factors in human rheumatoid arthritis gives support to the statement that autoimmune processes are involved in the etiology of rheumatoid arthritis in men."} {"id": "PMID:159608", "title": "[Experiences with the provocative inhalation test in occupationally induced allergic diseases of the respiratory tract (author's transl)].", "content": "Using simple technique we performed 1460 inhalation tests with occupational inhalation allergens. Before inhalation provocation testing all patients had been skin tested. In the case of organic allergens the inhalative test was positive in 20%, in the case of anorganic in 10%. The parameters should be measured in those cases causing immediate reaction until 30 minutes after inhalation and in those cases causing delayed reaction until 8 hours after the provocation test. A control test with the solvent is not necessary. The results of the inhalation test depend on the quality of allergen extracts.", "contents": "[Experiences with the provocative inhalation test in occupationally induced allergic diseases of the respiratory tract (author's transl)]. Using simple technique we performed 1460 inhalation tests with occupational inhalation allergens. Before inhalation provocation testing all patients had been skin tested. In the case of organic allergens the inhalative test was positive in 20%, in the case of anorganic in 10%. The parameters should be measured in those cases causing immediate reaction until 30 minutes after inhalation and in those cases causing delayed reaction until 8 hours after the provocation test. A control test with the solvent is not necessary. The results of the inhalation test depend on the quality of allergen extracts."} {"id": "PMID:159618", "title": "Left ventricular function at rest and during exercise after aortic valve replacement in patients with aortic regurgitation.", "content": "To determine the effect of aortic valve replacement on reversing abnormalities of left ventricular function in patients with aortic regurgitation, radionuclide cineangiography was used to study 16 sympatomatic patients with aortic regurgitation before and 6 months after aortic valve replacement. Before operation, left ventricular ejection fraction was 46 +/- 3 percent at rest (normal mean +/- standard error of the mean 57 +/- 1 percent; P less than 0.001), and decreased to 37 +/- 4 percent during exercise (normal 71 +/- 2 percent; P less than 0.001). after operation, ejection fraction rose to 58 +/- 4 percent at rest, indistinguishable from the normal value, and during exercise was 53 +/- 4 percent, increased (P less than 0.001) from before operation but significantly (P less than 0.001) subnormal. Thus, aortic valve replacement can improve but usually does not normalize left ventricular function during exercise in symptomatic patients with aortic regurgitation.", "contents": "Left ventricular function at rest and during exercise after aortic valve replacement in patients with aortic regurgitation. To determine the effect of aortic valve replacement on reversing abnormalities of left ventricular function in patients with aortic regurgitation, radionuclide cineangiography was used to study 16 sympatomatic patients with aortic regurgitation before and 6 months after aortic valve replacement. Before operation, left ventricular ejection fraction was 46 +/- 3 percent at rest (normal mean +/- standard error of the mean 57 +/- 1 percent; P less than 0.001), and decreased to 37 +/- 4 percent during exercise (normal 71 +/- 2 percent; P less than 0.001). after operation, ejection fraction rose to 58 +/- 4 percent at rest, indistinguishable from the normal value, and during exercise was 53 +/- 4 percent, increased (P less than 0.001) from before operation but significantly (P less than 0.001) subnormal. Thus, aortic valve replacement can improve but usually does not normalize left ventricular function during exercise in symptomatic patients with aortic regurgitation."} {"id": "PMID:159619", "title": "Myocardial contractile function in aortic stenosis as determined from the rate of stress development during isovolumic systole.", "content": "To assess myocardial contractile function in the chronically hypertrophied human left ventricle, the rate of stress development (dsigma/dt) as a function of developed stress (sigmaD) during isovolumic systole was examined. Results for eight patients with aortic stenosis were compared with those for seven subjects with normal left ventricular function and with those for five patients with idiopathic congestive cardiomyopathy. The rate of stress development (dsigma/dt) was nearly identical in patients with aortic stenosis and in normal subjects over a wide range of values of sigmaD but was significantly lower in patients with cardiomyopathy (P less than 0.01 versus control subjects and patients with aortic stenosis). Normal values for dsigma/dt held not only for patients with compensated pressure overload, but also for those patients with aortic stenosis with depressed left ventricular ejection fraction and overt congestive failure. Similar findings were obtained when the first derivative of left ventricular pressure (dP/dt) was examined as a function of developed left ventricular pressure in normal subjects and patients with aortic stenosis or cardiomyopathy. These results indicate that contractile function as characterized by the isovolumic rate of stress development is not necessarily impaired in chronic pressure overload hypertrophy.", "contents": "Myocardial contractile function in aortic stenosis as determined from the rate of stress development during isovolumic systole. To assess myocardial contractile function in the chronically hypertrophied human left ventricle, the rate of stress development (dsigma/dt) as a function of developed stress (sigmaD) during isovolumic systole was examined. Results for eight patients with aortic stenosis were compared with those for seven subjects with normal left ventricular function and with those for five patients with idiopathic congestive cardiomyopathy. The rate of stress development (dsigma/dt) was nearly identical in patients with aortic stenosis and in normal subjects over a wide range of values of sigmaD but was significantly lower in patients with cardiomyopathy (P less than 0.01 versus control subjects and patients with aortic stenosis). Normal values for dsigma/dt held not only for patients with compensated pressure overload, but also for those patients with aortic stenosis with depressed left ventricular ejection fraction and overt congestive failure. Similar findings were obtained when the first derivative of left ventricular pressure (dP/dt) was examined as a function of developed left ventricular pressure in normal subjects and patients with aortic stenosis or cardiomyopathy. These results indicate that contractile function as characterized by the isovolumic rate of stress development is not necessarily impaired in chronic pressure overload hypertrophy."} {"id": "PMID:159620", "title": "Avicenna's view on cancer from his Canon.", "content": "Avicenna's views on cancer are presented from his Medical Canon. A literal translation from Arabic has been undertaken by the author. The clinical diagnosis, the prognosis as well as the therapeutic measures according to Avicenna are interesting to know and compare with our views one thousand years later.", "contents": "Avicenna's view on cancer from his Canon. Avicenna's views on cancer are presented from his Medical Canon. A literal translation from Arabic has been undertaken by the author. The clinical diagnosis, the prognosis as well as the therapeutic measures according to Avicenna are interesting to know and compare with our views one thousand years later."} {"id": "PMID:159621", "title": "Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions.", "content": "Calcium stimulates, and zinc inhibits, a wide variety of cell types. In the erythrocyte, we have found calcium and zinc to have antagonist actions in a variety of systems. An important mechanism for calcium effects on cells is activation of calmodulin. Calmodulin is a small ubiquitous protein which, when activated by calcium, has a large array of cellular regulatory functions. We now report that calmodulin function is inhibited by low concentrations of zinc. Zinc inhibition of calmodulin provides a rational molecular mechanism for the diverse cellular inhibitory effects of zinc, as well as for zinc's antagonism of calcium effects.", "contents": "Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions. Calcium stimulates, and zinc inhibits, a wide variety of cell types. In the erythrocyte, we have found calcium and zinc to have antagonist actions in a variety of systems. An important mechanism for calcium effects on cells is activation of calmodulin. Calmodulin is a small ubiquitous protein which, when activated by calcium, has a large array of cellular regulatory functions. We now report that calmodulin function is inhibited by low concentrations of zinc. Zinc inhibition of calmodulin provides a rational molecular mechanism for the diverse cellular inhibitory effects of zinc, as well as for zinc's antagonism of calcium effects."} {"id": "PMID:159622", "title": "Protecting the rights of the developmentally disabled: alternatives to the existing statutory and regulatory scheme.", "content": "The Developmentally Disabled Assistance and Bill of Rights Act of 1975 and related HEW regulations require each state to establish a system for the protection and advocacy of the rights of developmentally disabled persons as a condition to receiving specified federal funds. This Note contends that, under the present statutory and regulatory scheme, states and governors have broad powers to interfere with the proper functioning of protection and advocacy systems. The Note examines the principal legal remedies, contractual and constitutional, presently available to parties interested in reducing or eliminating such interference, and concludes that such remedies are ineffectual. Instead, the author proposes, the HEW regulations should be revised to strengthen the autonomy of protection and advocacy systems or, alternatively, Congress should amend the 1975 Act to provide for federal administration of such systems.", "contents": "Protecting the rights of the developmentally disabled: alternatives to the existing statutory and regulatory scheme. The Developmentally Disabled Assistance and Bill of Rights Act of 1975 and related HEW regulations require each state to establish a system for the protection and advocacy of the rights of developmentally disabled persons as a condition to receiving specified federal funds. This Note contends that, under the present statutory and regulatory scheme, states and governors have broad powers to interfere with the proper functioning of protection and advocacy systems. The Note examines the principal legal remedies, contractual and constitutional, presently available to parties interested in reducing or eliminating such interference, and concludes that such remedies are ineffectual. Instead, the author proposes, the HEW regulations should be revised to strengthen the autonomy of protection and advocacy systems or, alternatively, Congress should amend the 1975 Act to provide for federal administration of such systems."} {"id": "PMID:159625", "title": "Differentiation and regulation of peripheral androgen metabolism in rats and rhesus monkeys.", "content": "The sex-unique metabolic network for steroids is induced neonatally in male rats. The metabolic clearance rates (MCR) of dehydroepiandrosterone and testosterone are similar for both sexes of rats despite quantitatively significant sex differences in individual enzyme activities of adults; neonatally androgenized females had a 2-to 3-fold increase in MCR but cyproterone had no effect. The MCRT and MCRDHA of castrated adult male rhesus monkeys are the same as those of normal males; the MCRDHA is 4-fold greater. Testosterone treatment suppressed the MCRDHA of the castrated groups but estradiol treatment did not. The sex-steroid binding protein (SBP) levels were lower in males than females, and these values were reduced by testosterone. Estrogen suppressed the higher SBP values of females. The sex-steroid milieu of adult rhesus monkeys regulates SBP binding capacity and the enzyme activities of skin measured in vitro. Prenatal testosterone does not exert a crucial role in presetting the peripheral metabolic network in rhesus monkeys.", "contents": "Differentiation and regulation of peripheral androgen metabolism in rats and rhesus monkeys. The sex-unique metabolic network for steroids is induced neonatally in male rats. The metabolic clearance rates (MCR) of dehydroepiandrosterone and testosterone are similar for both sexes of rats despite quantitatively significant sex differences in individual enzyme activities of adults; neonatally androgenized females had a 2-to 3-fold increase in MCR but cyproterone had no effect. The MCRT and MCRDHA of castrated adult male rhesus monkeys are the same as those of normal males; the MCRDHA is 4-fold greater. Testosterone treatment suppressed the MCRDHA of the castrated groups but estradiol treatment did not. The sex-steroid binding protein (SBP) levels were lower in males than females, and these values were reduced by testosterone. Estrogen suppressed the higher SBP values of females. The sex-steroid milieu of adult rhesus monkeys regulates SBP binding capacity and the enzyme activities of skin measured in vitro. Prenatal testosterone does not exert a crucial role in presetting the peripheral metabolic network in rhesus monkeys."} {"id": "PMID:159626", "title": "Ischemic myocardial injury after exercise stress in the pressure-overloaded heart.", "content": "Systemic hemodynamics and regional myocardial blood flows were determined in 18 miniswine during the development of pressure-overload hypertrophy induced by supravalvular aortic constriction. Nine miniswine served as control animals. Regional myocardial blood flows were measured at rest and during exercise stress with radioactive microspheres after 2 days and 1 month of aortic constriction. Exercise stress, causing the heart rate to increase to 85% of its maximum, was imposed twice weekly for 5 minutes on 13 pressure-overloaded animals to elicit differences between the control and experimental groups that might not occur at rest. At rest, regional myocardial blood flows of pressure-overloaded animals were similar to those of control animals. When exercise stress was imposed after 2 days and 1 month of pressure overload, endocardial blood flows decreased 45% below control exercise levels, although epicardial blood flows were unchanged. During the first 2 weeks of pressure overload epicardial and endocardial electrocardiograms showed S-T segment elevation with exercise stress but not at rest. Postmortem examinations after 1 month of pressure overload showed significant histologic evidence of myocardial injury, namely, fibrosis, which was subendocardially located. These findings indicate that the pressure-overloaded heart is at risk for ischemic injury, particularly during the early, uncompensated stage.", "contents": "Ischemic myocardial injury after exercise stress in the pressure-overloaded heart. Systemic hemodynamics and regional myocardial blood flows were determined in 18 miniswine during the development of pressure-overload hypertrophy induced by supravalvular aortic constriction. Nine miniswine served as control animals. Regional myocardial blood flows were measured at rest and during exercise stress with radioactive microspheres after 2 days and 1 month of aortic constriction. Exercise stress, causing the heart rate to increase to 85% of its maximum, was imposed twice weekly for 5 minutes on 13 pressure-overloaded animals to elicit differences between the control and experimental groups that might not occur at rest. At rest, regional myocardial blood flows of pressure-overloaded animals were similar to those of control animals. When exercise stress was imposed after 2 days and 1 month of pressure overload, endocardial blood flows decreased 45% below control exercise levels, although epicardial blood flows were unchanged. During the first 2 weeks of pressure overload epicardial and endocardial electrocardiograms showed S-T segment elevation with exercise stress but not at rest. Postmortem examinations after 1 month of pressure overload showed significant histologic evidence of myocardial injury, namely, fibrosis, which was subendocardially located. These findings indicate that the pressure-overloaded heart is at risk for ischemic injury, particularly during the early, uncompensated stage."} {"id": "PMID:159630", "title": "Congenital duodenal obstruction. A review of 65 cases.", "content": "We report our experience with 65 patients with congenital duodenal obstruction, 36 with intrinsic and 29 with extrinsic lesions. Seventeen patients had trisomy 21 syndrome. Eight pregnancies were complicated by polyhydramnios. The diagnostic features encountered, the operative procedures used, and the postoperative management regimes used are presented. Thirty-two of the 36 patients with intrinsic lesions and 28 of the 29 patients with extrinsic lesions survived. The data on the five patients who died emphasize the effect of multiple congenital anomalies and prematurity on survival. This review suggests that the surgical procedures available for treating patients with congenital duodenal obstruction are well established and yield predictably good results.", "contents": "Congenital duodenal obstruction. A review of 65 cases. We report our experience with 65 patients with congenital duodenal obstruction, 36 with intrinsic and 29 with extrinsic lesions. Seventeen patients had trisomy 21 syndrome. Eight pregnancies were complicated by polyhydramnios. The diagnostic features encountered, the operative procedures used, and the postoperative management regimes used are presented. Thirty-two of the 36 patients with intrinsic lesions and 28 of the 29 patients with extrinsic lesions survived. The data on the five patients who died emphasize the effect of multiple congenital anomalies and prematurity on survival. This review suggests that the surgical procedures available for treating patients with congenital duodenal obstruction are well established and yield predictably good results."} {"id": "PMID:159631", "title": "Use of Doppler ultrasound in intestinal surgery.", "content": "Doppler ultrasonography was used intraoperatively in 117 patients undergoing intestinal anastomosis or enterostomy to determine the adequacy of blood supply at the margins of resection. Doppler findings were compared with clinical assessment of intestinal blood flow by the operating surgeon. In 92 per cent of cases, Doppler signals and clinical observation coincided. However, in five of six cases in which Doppler signals were absent at one margin, the surgeon resected additional intestine, selecting margins within 1 cm of the nearest arterial Doppler signal. All five patients had uneventful healing. In the one case in which the surgeon chose to rely onthe appearance of the bowel despite the absence of Doppler arterial signals, ischemic necrosis of the proximal segment and anastomotic disruption occurred. The technique of Doppler ultrasonography is readily learned, and the instrument is available in most hospitals. Intraoperative use of Doppler ultrasonography can help identify intestine lacking a blood supply adequate to assure viability before changes in the appearance of the bowel alert the surgeon to the problem.", "contents": "Use of Doppler ultrasound in intestinal surgery. Doppler ultrasonography was used intraoperatively in 117 patients undergoing intestinal anastomosis or enterostomy to determine the adequacy of blood supply at the margins of resection. Doppler findings were compared with clinical assessment of intestinal blood flow by the operating surgeon. In 92 per cent of cases, Doppler signals and clinical observation coincided. However, in five of six cases in which Doppler signals were absent at one margin, the surgeon resected additional intestine, selecting margins within 1 cm of the nearest arterial Doppler signal. All five patients had uneventful healing. In the one case in which the surgeon chose to rely onthe appearance of the bowel despite the absence of Doppler arterial signals, ischemic necrosis of the proximal segment and anastomotic disruption occurred. The technique of Doppler ultrasonography is readily learned, and the instrument is available in most hospitals. Intraoperative use of Doppler ultrasonography can help identify intestine lacking a blood supply adequate to assure viability before changes in the appearance of the bowel alert the surgeon to the problem."} {"id": "PMID:159648", "title": "A study of the effect of pregnancy on muscle fibers of the rectus abdominis muscle of the rat.", "content": "Samples of the rectus abdominis muscle were taken from Sprague-Dawley rats at 0, 3, 6, 6, 12, 15, 18, and 21 days of pregnancy, and at 1, 3, 6, 9, 12, and 15 days of postpartum. Sections were incubated for actomyosin adenosine triphosphatase activity following preincubation at a basic pH. Muscle fibers within a unit area of each sample were identified as to fiber type according to their enzyme activity, and the population of each type counted. The proportion of each fiber type was calculated and the diameter of 24 fibers of each type measured. No changes were noted in the muscle fiber proportions through the course of the experiment. Differential changes in muscle fiber diameters were noted in each of the three muscle fiber types. Slow oxidative fibers underwent an increase in diameter through the last half of pregnancy. The diameter was further increased as stretch of the muscle was released after birth, and did not decrease in the postpartum period. Fast glycolytic fibers decreased in diameter during the last half of pregnancy, but returned to the prepregnancy diameter in the first postpartum day. The diameter of the fast oxidative glycolytic fibers remained unchanged through the course of pregnacy and in the postpartum period.", "contents": "A study of the effect of pregnancy on muscle fibers of the rectus abdominis muscle of the rat. Samples of the rectus abdominis muscle were taken from Sprague-Dawley rats at 0, 3, 6, 6, 12, 15, 18, and 21 days of pregnancy, and at 1, 3, 6, 9, 12, and 15 days of postpartum. Sections were incubated for actomyosin adenosine triphosphatase activity following preincubation at a basic pH. Muscle fibers within a unit area of each sample were identified as to fiber type according to their enzyme activity, and the population of each type counted. The proportion of each fiber type was calculated and the diameter of 24 fibers of each type measured. No changes were noted in the muscle fiber proportions through the course of the experiment. Differential changes in muscle fiber diameters were noted in each of the three muscle fiber types. Slow oxidative fibers underwent an increase in diameter through the last half of pregnancy. The diameter was further increased as stretch of the muscle was released after birth, and did not decrease in the postpartum period. Fast glycolytic fibers decreased in diameter during the last half of pregnancy, but returned to the prepregnancy diameter in the first postpartum day. The diameter of the fast oxidative glycolytic fibers remained unchanged through the course of pregnacy and in the postpartum period."} {"id": "PMID:159649", "title": "Pulmonary hypertension complicating portal hypertension.", "content": "We report 9 patients with pulmonary hypertension complicating portal hypertension. The cause of portal hypertension was cirrhosis in 7 patients, nodular regenerative hyperplasia of the liver in 1, and portal vein obstruction in 1. Six patients had been treated by portal-systemic shunting before the clinical onset of pulmonary hypertension. The interval between the first manifestation of portal hypertension and the recognition of pulmonary hypertension ranged from 2 to 15 years. Histologic examination in 1 of these patients revealed medial hypertrophy, concentric intimal proliferation, and plexiform lesions affecting the small pulmonary arteries. Pulmonary hypertension might result from the effect of a vasoconstrictive agent on the small pulmonary arteries or of a substance toxic to the walls of these vessels that is produced in the splanchnic territory, destroyed by the liver in normal subjects, and reaches the pulmonary arteries through portal-systemic shunts in these patients.", "contents": "Pulmonary hypertension complicating portal hypertension. We report 9 patients with pulmonary hypertension complicating portal hypertension. The cause of portal hypertension was cirrhosis in 7 patients, nodular regenerative hyperplasia of the liver in 1, and portal vein obstruction in 1. Six patients had been treated by portal-systemic shunting before the clinical onset of pulmonary hypertension. The interval between the first manifestation of portal hypertension and the recognition of pulmonary hypertension ranged from 2 to 15 years. Histologic examination in 1 of these patients revealed medial hypertrophy, concentric intimal proliferation, and plexiform lesions affecting the small pulmonary arteries. Pulmonary hypertension might result from the effect of a vasoconstrictive agent on the small pulmonary arteries or of a substance toxic to the walls of these vessels that is produced in the splanchnic territory, destroyed by the liver in normal subjects, and reaches the pulmonary arteries through portal-systemic shunts in these patients."} {"id": "PMID:159650", "title": "Alterations in the ultrastructure of nonciliated bronchiolar epithelial (Clara) cells by streptozotocin-induced diabetes in rats.", "content": "Recent studies showed marked alterations in type II pneumocyte ultrastructure by streptozotocin-induced diabetes. To see whether other pulmonary epithelium is affected, we examined terminal bronchioles by transmission electron microscopy. Ten adult male rats received one intrajugular injection of streptozotocin (75 mg/kg of body weight) and were killed 14 days later. As control subjects, 5 additional rats received only saline, and 5 rats given streptozotocin injections received protamine zinc insulin (1 unit/rat/day). As compared to lungs of control animals, the bronchiolar epithelial cell type most altered in diabetic rat lungs was the Clara cell. The numbers of ovoid secretory granules decreased significantly (29 of 57 cells were without granules versus 0 of 78 in control animals), and the number of rod-shaped granules increased. Administration of exogenous insulin alleviated the changes. These findings show that the changes in pulmonary metabolic function associated with diabetes mellitus result from alterations not only in granular pneumocytes, but also in nonciliated, bronchiolar secretory epithelial (Clara) cells.", "contents": "Alterations in the ultrastructure of nonciliated bronchiolar epithelial (Clara) cells by streptozotocin-induced diabetes in rats. Recent studies showed marked alterations in type II pneumocyte ultrastructure by streptozotocin-induced diabetes. To see whether other pulmonary epithelium is affected, we examined terminal bronchioles by transmission electron microscopy. Ten adult male rats received one intrajugular injection of streptozotocin (75 mg/kg of body weight) and were killed 14 days later. As control subjects, 5 additional rats received only saline, and 5 rats given streptozotocin injections received protamine zinc insulin (1 unit/rat/day). As compared to lungs of control animals, the bronchiolar epithelial cell type most altered in diabetic rat lungs was the Clara cell. The numbers of ovoid secretory granules decreased significantly (29 of 57 cells were without granules versus 0 of 78 in control animals), and the number of rod-shaped granules increased. Administration of exogenous insulin alleviated the changes. These findings show that the changes in pulmonary metabolic function associated with diabetes mellitus result from alterations not only in granular pneumocytes, but also in nonciliated, bronchiolar secretory epithelial (Clara) cells."} {"id": "PMID:159651", "title": "The anatomic rationale for abdominal lipectomy.", "content": "Changes occur in the vascular and lymphatic flow and in the sensory pattern of the superficial abdominal wall during abdominal lipectomy. The development of these systems, their anatomic descriptions in the abdominal wall, and the changes created by the surgery are documented to explain tissue survival following the procedure.", "contents": "The anatomic rationale for abdominal lipectomy. Changes occur in the vascular and lymphatic flow and in the sensory pattern of the superficial abdominal wall during abdominal lipectomy. The development of these systems, their anatomic descriptions in the abdominal wall, and the changes created by the surgery are documented to explain tissue survival following the procedure."} {"id": "PMID:159652", "title": "[Pulmonary atresia with intact ventricular septum (author's transl)].", "content": "Ten cases of pulmonary atresia with intact ventricular septum are presented. The groups in which these patients are classified are described, thinking that the mentioned classification is a simplification of the problem. After discussion of the dates apported by clinic, thorax X-Rays and electrocardiogram, authors come to the conclusion that they are not specific of this cardiopathy. Contribution of hemodinamic and angiocardiographic characteristics, paying special attention to the blood flow to lung vascular tree and in existance of intramyocardium sinusoid are shown. Description of the general tendencies of the most accepted surgical techniques in bibliography for resolution of both groups of patients is made.", "contents": "[Pulmonary atresia with intact ventricular septum (author's transl)]. Ten cases of pulmonary atresia with intact ventricular septum are presented. The groups in which these patients are classified are described, thinking that the mentioned classification is a simplification of the problem. After discussion of the dates apported by clinic, thorax X-Rays and electrocardiogram, authors come to the conclusion that they are not specific of this cardiopathy. Contribution of hemodinamic and angiocardiographic characteristics, paying special attention to the blood flow to lung vascular tree and in existance of intramyocardium sinusoid are shown. Description of the general tendencies of the most accepted surgical techniques in bibliography for resolution of both groups of patients is made."} {"id": "PMID:159654", "title": "Susceptibility-resistance pattern of Neisseria meningitidis isolated in the province of Ontario, Canada.", "content": "A total of 522 N. meningitidis cultures isolated from different sources (cerebrospinal fluid, sputum, blood, naso-pharyngeal, uro-genital area, eye and rectal samples) between the years 1976-1977 in Ontario, were tested for their susceptibility pattern to 8 antibacterial drugs. Among the 522 cultures, 24.8% showed resistance to sulfadiazine (10-100 micrograns/ml) and all N. meningitidis cultures (100%) were resistant to spectinomycin (15 micrograms/ml); this feature could be used as one of the confirmation tests for N. meningitidis, especially with the strains which cause difficulty in identification and/or confirmation. Among the N. meningitidis cultures, 3.2% yielded maltose negative results in CTA sugars (cystine trypticase agar) and were also susceptible to sulfadiazine (10 micrograms/ml).", "contents": "Susceptibility-resistance pattern of Neisseria meningitidis isolated in the province of Ontario, Canada. A total of 522 N. meningitidis cultures isolated from different sources (cerebrospinal fluid, sputum, blood, naso-pharyngeal, uro-genital area, eye and rectal samples) between the years 1976-1977 in Ontario, were tested for their susceptibility pattern to 8 antibacterial drugs. Among the 522 cultures, 24.8% showed resistance to sulfadiazine (10-100 micrograns/ml) and all N. meningitidis cultures (100%) were resistant to spectinomycin (15 micrograms/ml); this feature could be used as one of the confirmation tests for N. meningitidis, especially with the strains which cause difficulty in identification and/or confirmation. Among the N. meningitidis cultures, 3.2% yielded maltose negative results in CTA sugars (cystine trypticase agar) and were also susceptible to sulfadiazine (10 micrograms/ml)."} {"id": "PMID:159655", "title": "[Norwegian scabies: etiological grounds (author's transl)].", "content": "Norwegian scabies is a rare clinical variant of human infestation with Sarcoptes scabiei var. hominis. It is characterized by hyperkeratotic lesions of the palmar and plantar surfaces, scalp and ears which contain myriad mites. The authors have observed three cases: the first occurred in a old delibited woman with a Recklinghausen's disease, the second in a boy with Down's syndrome, the last in a child treated with immunosuppressors. Review of the literature and study of etiological grounds. The pathogenesis is yet unclear but the altered host factors appear to be the principal determinant: primary or secondary specific immunologic deficit and inability to eliminate the mites because of the absence of scratching, hereditary predisposition to keratotic reaction of the skin.", "contents": "[Norwegian scabies: etiological grounds (author's transl)]. Norwegian scabies is a rare clinical variant of human infestation with Sarcoptes scabiei var. hominis. It is characterized by hyperkeratotic lesions of the palmar and plantar surfaces, scalp and ears which contain myriad mites. The authors have observed three cases: the first occurred in a old delibited woman with a Recklinghausen's disease, the second in a boy with Down's syndrome, the last in a child treated with immunosuppressors. Review of the literature and study of etiological grounds. The pathogenesis is yet unclear but the altered host factors appear to be the principal determinant: primary or secondary specific immunologic deficit and inability to eliminate the mites because of the absence of scratching, hereditary predisposition to keratotic reaction of the skin."} {"id": "PMID:159666", "title": "Pseudomonas aeruginosa gram-negative folliculitis.", "content": "Three patients with sudden, unmanageable exacerbation of acne vulgaris were shown to have Gram-negative folliculitis due to Pseudomonas aeruginosa. In each patient, the source of the Pseudomonas proved to be an otitis externa infection. In contrast to previous cases of Gram-negative folliculitis due to Proteus, Escherichia coli, or Klebsiella, the anterior nares were not colonized. Treatment of the otitis externa and the Gram-negative folliculitis with acetic acid compresses and topical antibiotics led to prompt resolution without recurrence.", "contents": "Pseudomonas aeruginosa gram-negative folliculitis. Three patients with sudden, unmanageable exacerbation of acne vulgaris were shown to have Gram-negative folliculitis due to Pseudomonas aeruginosa. In each patient, the source of the Pseudomonas proved to be an otitis externa infection. In contrast to previous cases of Gram-negative folliculitis due to Proteus, Escherichia coli, or Klebsiella, the anterior nares were not colonized. Treatment of the otitis externa and the Gram-negative folliculitis with acetic acid compresses and topical antibiotics led to prompt resolution without recurrence."} {"id": "PMID:159667", "title": "Contact urticaria to parabens.", "content": "Contact urticaria developed in a patient after topical application of paraben-containing compounds. Positive open patch test results and a positive passive transfer (Prausnitz-K\u00fcstner reaction) test demonstrated an immunologic mechanism for the patient's skin reaction. The importance of parabens to contact urticaria is described.", "contents": "Contact urticaria to parabens. Contact urticaria developed in a patient after topical application of paraben-containing compounds. Positive open patch test results and a positive passive transfer (Prausnitz-K\u00fcstner reaction) test demonstrated an immunologic mechanism for the patient's skin reaction. The importance of parabens to contact urticaria is described."} {"id": "PMID:159670", "title": "Persistent photosensitivity following occupational exposure to epoxy resin.", "content": "Persistent photosensitivity developed in eight men following occupational exposure to hot epoxy resin fumes. The condition was limited to sites the resin contacted. Small doses of ultraviolet-A light (2 to 5 joules/sq cm) evoked abnormal reactions consisting of erythema, edema, and papules in the clinically involved skin. Positive photopatch tests to epoxy resin were observed in four subjects, and to 4, 4'-isopropylidenediphenol (Bisphenol A) in all. The photosensitivity is most probably due to photocontact allergy to 4,4'-isopropylidenediphenol or to a closely related chemical.", "contents": "Persistent photosensitivity following occupational exposure to epoxy resin. Persistent photosensitivity developed in eight men following occupational exposure to hot epoxy resin fumes. The condition was limited to sites the resin contacted. Small doses of ultraviolet-A light (2 to 5 joules/sq cm) evoked abnormal reactions consisting of erythema, edema, and papules in the clinically involved skin. Positive photopatch tests to epoxy resin were observed in four subjects, and to 4, 4'-isopropylidenediphenol (Bisphenol A) in all. The photosensitivity is most probably due to photocontact allergy to 4,4'-isopropylidenediphenol or to a closely related chemical."} {"id": "PMID:159671", "title": "Idiopathic pigmentation of the hands. Professional exogenous ochronosis? A new entity?", "content": "A case of ochronosis-like pigmentation of the hands is described. The following criteria were fulfilled: (1) presence of blue to black spots confined to the hands: (2) pitch-black macroscopic appearance of the biopsy specimen; (3) abundance of granular material in the whole connective structures on microscopic examination of an unstained specimen just mounted on a slide; (4) numerous pigmented granules in the elastic and collagen fibers: (5) no family history, abnormal coloration of the urine, taking of drugs, or rheumatism; (6) onset in a manual worker exposed to benzenic substances. This seems to be a new entity, probably a variant of exogenous ochronosis produced by professional contacts with some agents and perhaps a professional benzenic ochronosis.", "contents": "Idiopathic pigmentation of the hands. Professional exogenous ochronosis? A new entity? A case of ochronosis-like pigmentation of the hands is described. The following criteria were fulfilled: (1) presence of blue to black spots confined to the hands: (2) pitch-black macroscopic appearance of the biopsy specimen; (3) abundance of granular material in the whole connective structures on microscopic examination of an unstained specimen just mounted on a slide; (4) numerous pigmented granules in the elastic and collagen fibers: (5) no family history, abnormal coloration of the urine, taking of drugs, or rheumatism; (6) onset in a manual worker exposed to benzenic substances. This seems to be a new entity, probably a variant of exogenous ochronosis produced by professional contacts with some agents and perhaps a professional benzenic ochronosis."} {"id": "PMID:159673", "title": "Effect of 5-hydroxytryptophan on muricide response induced by thiamine deficiency.", "content": "Male Wistar rats maintained on a thiamine deficient diet showed the mouse-killing response (muricide). On the 30th day of experimental feeding, the incidence of the muricide response was 78% in the thiamine deficient group. Intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) suppressed the muricide response in a dose-dependent manner. The suppressive effect of 5-HTP on the muricide response was potentiated by pretreatment with Ro4-4602. On the 20th day of experimental feeding, the incidence of the muricide response was 42.9% in the thiamine deficient group, 14.3% in the pair-fed group and 0% in the control group, respectively. The incidence increased to 92.5% in the thiamine deficient rats 24 hr after the i.p. injection of 100 mg/kg parachlorophenylalanine. The results of the present sutdy indicate that the injection of 5-HTP was effective in suppressing the muricide response induced by thiamine deficiency.", "contents": "Effect of 5-hydroxytryptophan on muricide response induced by thiamine deficiency. Male Wistar rats maintained on a thiamine deficient diet showed the mouse-killing response (muricide). On the 30th day of experimental feeding, the incidence of the muricide response was 78% in the thiamine deficient group. Intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) suppressed the muricide response in a dose-dependent manner. The suppressive effect of 5-HTP on the muricide response was potentiated by pretreatment with Ro4-4602. On the 20th day of experimental feeding, the incidence of the muricide response was 42.9% in the thiamine deficient group, 14.3% in the pair-fed group and 0% in the control group, respectively. The incidence increased to 92.5% in the thiamine deficient rats 24 hr after the i.p. injection of 100 mg/kg parachlorophenylalanine. The results of the present sutdy indicate that the injection of 5-HTP was effective in suppressing the muricide response induced by thiamine deficiency."} {"id": "PMID:159674", "title": "Immune-complex deposition in the eye in systemic lupus erythematosus.", "content": "A patient with systemic lupus erythematosus (SLE) and lupus retinopathy showed resolution of subretinal edema documented with fluorescein angiography. Subsequently at autopsy, immunofluorescence studies disclosed ocular deposition of immunoglobulins in the vascular layer of choroid capillaries and basement membranes of ciliary processes and bulbar conjunctivas. To our knowledge, these findings represent the first reported documentation of probable immune-complex ocular vasculitis in lupus retinopathy using immunofluorescent techniques, and they support the hypothesis that lupus retinopathy is caused by immune complex deposition as are other manifestations of SLE.", "contents": "Immune-complex deposition in the eye in systemic lupus erythematosus. A patient with systemic lupus erythematosus (SLE) and lupus retinopathy showed resolution of subretinal edema documented with fluorescein angiography. Subsequently at autopsy, immunofluorescence studies disclosed ocular deposition of immunoglobulins in the vascular layer of choroid capillaries and basement membranes of ciliary processes and bulbar conjunctivas. To our knowledge, these findings represent the first reported documentation of probable immune-complex ocular vasculitis in lupus retinopathy using immunofluorescent techniques, and they support the hypothesis that lupus retinopathy is caused by immune complex deposition as are other manifestations of SLE."} {"id": "PMID:159675", "title": "[How essential are essential fatty acids?].", "content": "The present article analyzes the symptoms of essential fatty acid deficiency, both in human beings and in animals. The first part of the article describes the interrelationships between linoleic, linolenic and arachidonic acids, and how these acids affect the physiological response in experimental animals. Likewise, it discusses the effect of gradual levels of linoleic acid intake, and its use to establish quantitative requirements for essential fatty acids on the basis of biochemical parameters. It provides information also on the effect of dietary non-essential fatty acids on essential fatty acid metabolism. The second part of the article deals with the significance of essential fatty acids in human nutrition. In spite of the available information in this regard, it is suggested that further and more thorough studies be conducted. Data on human blood serum fatty acid composition are presented, which could be used as a basis for comparison when essential fatty acid deficiency is suspected. The author further indicates that there are several dietary factors that could induce essential fatty acid deficiency, or that could result in marginal states of deficiency in these nutrients.", "contents": "[How essential are essential fatty acids?]. The present article analyzes the symptoms of essential fatty acid deficiency, both in human beings and in animals. The first part of the article describes the interrelationships between linoleic, linolenic and arachidonic acids, and how these acids affect the physiological response in experimental animals. Likewise, it discusses the effect of gradual levels of linoleic acid intake, and its use to establish quantitative requirements for essential fatty acids on the basis of biochemical parameters. It provides information also on the effect of dietary non-essential fatty acids on essential fatty acid metabolism. The second part of the article deals with the significance of essential fatty acids in human nutrition. In spite of the available information in this regard, it is suggested that further and more thorough studies be conducted. Data on human blood serum fatty acid composition are presented, which could be used as a basis for comparison when essential fatty acid deficiency is suspected. The author further indicates that there are several dietary factors that could induce essential fatty acid deficiency, or that could result in marginal states of deficiency in these nutrients."} {"id": "PMID:159676", "title": "[Operated aortic stenosis. Evaluation of the long-term prognosis using clinical and hemodynamic parameters in a series of 249 cases].", "content": "The long-term results and the prognostic factors in aortic valve replacement for aortic stenosis were assessed from a series of 249 operated cases (comprising 199 pure or dominant stenosis and 50 mixed aortic lesions) followed up for a maximal period of 9 years. The postoperative survival rate, 71% at 5 years, 62,6% at 8 years, including the operative mortality, is better than in a comparable series of pure chronic aortic incompetence (58% at 5 years) despite a higher average age. In the same age group the difference is significant at the 6th year. However, no difference was observed between mixed aortic disease and aortic stenosis. Irreversible myocardial dysfunction is relatively rare (6,6% of survivors at 1 month, 24% of poor results or late deaths) and much less common than in aortic incompetence of which it represents the main cause of failure. Even in these cases, prolonged symptomatic improvement may be observed. 3 prognostic factors affect the operative and late mortality. They act to variable degrees and independantly of each other. They are : age, cardiomegaly and heart failure. The actuarial 5 year survival is: 81,77% and 53% for under 50, 50 to 65 and over 65 years age group respectively; 88%, 78% and 48% for cardiothoracic ratios of less than 0,50, between 0,50 and 0,58 and greater than 0,58 respectively; 83%, 65% and 47% for patients without signs of heart failure, with a history of pulmonary oedema, and with a history of congestive cardiac failure respectively. These results encourage a liberal attitude towards surgery, even in old patients with severe valvular lesions.", "contents": "[Operated aortic stenosis. Evaluation of the long-term prognosis using clinical and hemodynamic parameters in a series of 249 cases]. The long-term results and the prognostic factors in aortic valve replacement for aortic stenosis were assessed from a series of 249 operated cases (comprising 199 pure or dominant stenosis and 50 mixed aortic lesions) followed up for a maximal period of 9 years. The postoperative survival rate, 71% at 5 years, 62,6% at 8 years, including the operative mortality, is better than in a comparable series of pure chronic aortic incompetence (58% at 5 years) despite a higher average age. In the same age group the difference is significant at the 6th year. However, no difference was observed between mixed aortic disease and aortic stenosis. Irreversible myocardial dysfunction is relatively rare (6,6% of survivors at 1 month, 24% of poor results or late deaths) and much less common than in aortic incompetence of which it represents the main cause of failure. Even in these cases, prolonged symptomatic improvement may be observed. 3 prognostic factors affect the operative and late mortality. They act to variable degrees and independantly of each other. They are : age, cardiomegaly and heart failure. The actuarial 5 year survival is: 81,77% and 53% for under 50, 50 to 65 and over 65 years age group respectively; 88%, 78% and 48% for cardiothoracic ratios of less than 0,50, between 0,50 and 0,58 and greater than 0,58 respectively; 83%, 65% and 47% for patients without signs of heart failure, with a history of pulmonary oedema, and with a history of congestive cardiac failure respectively. These results encourage a liberal attitude towards surgery, even in old patients with severe valvular lesions."} {"id": "PMID:159677", "title": "Input modes: their importance in the clinical application of electronic aids for disabled persons.", "content": "In this study of techniques for the operation of environmental control aids for disabled persons, 12 programmed input modes were investigated in a uniform typing task. A microprocessor-based electronic aid (MECON) developed for this project was operated in 1 mode at a time by the disabled subject using a joystick and/or switch. Fourteen severely handicapped subjects with a wide variety of disabling conditions participated in the investigation. In the results, various input modes were ranked in order of speed. The fit and stability of the transducer were found to be important to the subjects' performance, and there were a number of indications that the availability of multiple input modes for an aid is highly desirable.", "contents": "Input modes: their importance in the clinical application of electronic aids for disabled persons. In this study of techniques for the operation of environmental control aids for disabled persons, 12 programmed input modes were investigated in a uniform typing task. A microprocessor-based electronic aid (MECON) developed for this project was operated in 1 mode at a time by the disabled subject using a joystick and/or switch. Fourteen severely handicapped subjects with a wide variety of disabling conditions participated in the investigation. In the results, various input modes were ranked in order of speed. The fit and stability of the transducer were found to be important to the subjects' performance, and there were a number of indications that the availability of multiple input modes for an aid is highly desirable."} {"id": "PMID:159678", "title": "[Lymphatic bed of layers of the abdominal wall in the human inguinal area].", "content": "Lymphatic bed in the layers of the inguinal area was studied in connection with age in 70 human corpses. Polychromic injection of arteries, veins and lymphatic bed, staining of preparations after van Gieson, Weigert, with hematoxylin-eosin and morphometry were the methods applied. It was stated that lymphatic capillaries penetrate through all the layers forming the abdominal wall of the human inguinal area; they arrange interconnected networks in dermis, in external and internal oblique and transversal muscles and in their aponeuroses, as well as in fasciae and in the peritoneum. The lymphatic bed in question changes during ontogenesis. Age transformations of the lymphatic capillaries are in connection with functional loading on the anterior abdominal wall. Intraorganic connections existing between the lymphatic vessels of the anterior abdominal wall and the organs of the small pelvis (urinary bladder, uterus, rectum, etc.) are revealed, they are of a rather great interest for physicians.", "contents": "[Lymphatic bed of layers of the abdominal wall in the human inguinal area]. Lymphatic bed in the layers of the inguinal area was studied in connection with age in 70 human corpses. Polychromic injection of arteries, veins and lymphatic bed, staining of preparations after van Gieson, Weigert, with hematoxylin-eosin and morphometry were the methods applied. It was stated that lymphatic capillaries penetrate through all the layers forming the abdominal wall of the human inguinal area; they arrange interconnected networks in dermis, in external and internal oblique and transversal muscles and in their aponeuroses, as well as in fasciae and in the peritoneum. The lymphatic bed in question changes during ontogenesis. Age transformations of the lymphatic capillaries are in connection with functional loading on the anterior abdominal wall. Intraorganic connections existing between the lymphatic vessels of the anterior abdominal wall and the organs of the small pelvis (urinary bladder, uterus, rectum, etc.) are revealed, they are of a rather great interest for physicians."} {"id": "PMID:159681", "title": "Microvasculature of rabbit muscle spindles.", "content": "The microvasculature of the muscle spindle and its relationship to the microcirculation of teniussimus extrafusal muscle is described. Muscle spindles lie in close proximity and parallel to the central artery, vein, and nerve. The arterioles to spindle capillaries are third to fourth order branches of the central artery, whereas most arterioles to extrafusal capillaries are sixth to eighth order. Two or three capillaries enter each spindle. At least one entry consistently was encountered in the equatorial area near the sensory endings. Branches of intrafusal capillaries run longitudinally, anastomose with each other, and cradle the sensory zone in a longitudinal capillary loop. Capillaries in muscle spindles are larger than those in extrafusal muscle. These characteristic features are presumed to enhance the capability of these capillaries to provide sufficient circulation to the spindle, particularly to the region of the sensory endings.", "contents": "Microvasculature of rabbit muscle spindles. The microvasculature of the muscle spindle and its relationship to the microcirculation of teniussimus extrafusal muscle is described. Muscle spindles lie in close proximity and parallel to the central artery, vein, and nerve. The arterioles to spindle capillaries are third to fourth order branches of the central artery, whereas most arterioles to extrafusal capillaries are sixth to eighth order. Two or three capillaries enter each spindle. At least one entry consistently was encountered in the equatorial area near the sensory endings. Branches of intrafusal capillaries run longitudinally, anastomose with each other, and cradle the sensory zone in a longitudinal capillary loop. Capillaries in muscle spindles are larger than those in extrafusal muscle. These characteristic features are presumed to enhance the capability of these capillaries to provide sufficient circulation to the spindle, particularly to the region of the sensory endings."} {"id": "PMID:159683", "title": "The use of thymoxamine in eyelid retraction.", "content": "We observed substantial narrowing in 75% of fissures in patients with various types of lid retraction after topical application of aqueous 0.5% thymoxamine (moxisylyte). Even contralateral normal-appearing fissures in thyroid patients responded in this manner. The nonresponders in the lid retraction group included a patient with an orbital pseudotumor and patients with long-standing and stable euthyroid eye disease. No normal subjects' fissures responded greatly to thymoxamine. A substantial reduction in palpebral fissures was seen in all patients with thick extraocular muscles and in 14 of 18 (78%) of all fissures of thyroid patients; the average response was 2.3 mm. This effect may last for five hours after thymoxamine administration. Thymoxamine may be of use as a diagnostic test for thyroid eye disease, and if it can be modified to cause less ocular irritation, it may be beneficial in the medical treatment of eyelid retraction.", "contents": "The use of thymoxamine in eyelid retraction. We observed substantial narrowing in 75% of fissures in patients with various types of lid retraction after topical application of aqueous 0.5% thymoxamine (moxisylyte). Even contralateral normal-appearing fissures in thyroid patients responded in this manner. The nonresponders in the lid retraction group included a patient with an orbital pseudotumor and patients with long-standing and stable euthyroid eye disease. No normal subjects' fissures responded greatly to thymoxamine. A substantial reduction in palpebral fissures was seen in all patients with thick extraocular muscles and in 14 of 18 (78%) of all fissures of thyroid patients; the average response was 2.3 mm. This effect may last for five hours after thymoxamine administration. Thymoxamine may be of use as a diagnostic test for thyroid eye disease, and if it can be modified to cause less ocular irritation, it may be beneficial in the medical treatment of eyelid retraction."} {"id": "PMID:159686", "title": "Therapeutic evaluation of Elase as adjunctive therapy in the treatment of monilial vaginitis.", "content": "The effectiveness of a lytic enzyme preparation (Elase--Parke-Davis) plus natamycin (Pimafucin--Gist-Brocades) was compared to natamycin therapy alone in a controlled clinical trial involving 120 patients suffering from monilial vulvo-vaginitis. The results indicate that addition of Elase to a natamycin treatment regimen increases the effectiveness of therapy both with respect to alleviation of symptoms and to eradication of the organism as determined by vaginal culture in patients with acute infection and in those in whom infection is complicated by pregnancy or diabetes.", "contents": "Therapeutic evaluation of Elase as adjunctive therapy in the treatment of monilial vaginitis. The effectiveness of a lytic enzyme preparation (Elase--Parke-Davis) plus natamycin (Pimafucin--Gist-Brocades) was compared to natamycin therapy alone in a controlled clinical trial involving 120 patients suffering from monilial vulvo-vaginitis. The results indicate that addition of Elase to a natamycin treatment regimen increases the effectiveness of therapy both with respect to alleviation of symptoms and to eradication of the organism as determined by vaginal culture in patients with acute infection and in those in whom infection is complicated by pregnancy or diabetes."} {"id": "PMID:159698", "title": "An active-site-directed adenosine triphosphate analogue binds to the beta-subunits of factor F1 mitochondrial adenosine triphosphatase with its triphosphate moiety.", "content": "The reaction of the mixed anhydride of [3H]ATP and mesitylenecarboxylic acid and soluble mitochondrial adenosine triphosphatase is accompanied by the covalent binding of one molecule of the inhibitor to a molecule of the enzyme and results in the inhibition of adenosine triphosphatase activity by more than 90%. The electrophoresis of adenosine triphosphatase modified by reaction with the mixed anhydride of [3H]ATP and mesitylenecarboxylic acid in polyacrylamide gel in the presence of sodium dodecyl sulphate showed that the inhibitor is bound to the beta-subunit of the enzyme. The results suggest that ATP may also bind to the beta-subunit of the adenosine triphosphatase with its triphosphate moiety.", "contents": "An active-site-directed adenosine triphosphate analogue binds to the beta-subunits of factor F1 mitochondrial adenosine triphosphatase with its triphosphate moiety. The reaction of the mixed anhydride of [3H]ATP and mesitylenecarboxylic acid and soluble mitochondrial adenosine triphosphatase is accompanied by the covalent binding of one molecule of the inhibitor to a molecule of the enzyme and results in the inhibition of adenosine triphosphatase activity by more than 90%. The electrophoresis of adenosine triphosphatase modified by reaction with the mixed anhydride of [3H]ATP and mesitylenecarboxylic acid in polyacrylamide gel in the presence of sodium dodecyl sulphate showed that the inhibitor is bound to the beta-subunit of the enzyme. The results suggest that ATP may also bind to the beta-subunit of the adenosine triphosphatase with its triphosphate moiety."} {"id": "PMID:159696", "title": "Alterations in rat myocardial mechanics under Goldblatt hypertension and experimental aortic stenosis.", "content": "Left ventricular hypertrophy was induced in young male Wistar rats by unilateral renal artery constriction, either with (Goldblatt I [ = G I]) or without (Goldblatt II [ = G II]) simultaneous contralateral nephrectomy. An average increase in left ventricular weight of 55% and 18% respectively was reached within 4 weeks as compared with controls of the same age. Further increase in ventricular mass up to the 6-month stage was considerably dependent on the degree of inhibition of body growth of the experimental animals. Other rats underwent a stenosis of the Aorta ascendens (AO) with a reduction in diameter to 50%--60% of the original value, whereby a left ventricular hypertrophy of 10%--30% ensued. Isolated trabecular muscle strips of the left ventricle were examined 4, 8 and 24 weeks (G II), 4 and 8 weeks (G I), and 4 and 6 weeks (AO) after operation. Sham operations were performed for all models used.", "contents": "Alterations in rat myocardial mechanics under Goldblatt hypertension and experimental aortic stenosis. Left ventricular hypertrophy was induced in young male Wistar rats by unilateral renal artery constriction, either with (Goldblatt I [ = G I]) or without (Goldblatt II [ = G II]) simultaneous contralateral nephrectomy. An average increase in left ventricular weight of 55% and 18% respectively was reached within 4 weeks as compared with controls of the same age. Further increase in ventricular mass up to the 6-month stage was considerably dependent on the degree of inhibition of body growth of the experimental animals. Other rats underwent a stenosis of the Aorta ascendens (AO) with a reduction in diameter to 50%--60% of the original value, whereby a left ventricular hypertrophy of 10%--30% ensued. Isolated trabecular muscle strips of the left ventricle were examined 4, 8 and 24 weeks (G II), 4 and 8 weeks (G I), and 4 and 6 weeks (AO) after operation. Sham operations were performed for all models used."} {"id": "PMID:159697", "title": "Plasma renin activity and hypertrophy of the right ventricle in hypoxic rats.", "content": "A NaCl load in chronically hypoxic rats abolished the increase in plasma renin activity occurring in rats exposed to hypoxia of the same degree and duration but with normal NaCl intake. The parallel reduction in hypoxic hypertrophy of the right ventricle in NaCl-loaded rats could be considered as indirect evidence supporting the view that renin may be involved in the development of heart hypertrophy.", "contents": "Plasma renin activity and hypertrophy of the right ventricle in hypoxic rats. A NaCl load in chronically hypoxic rats abolished the increase in plasma renin activity occurring in rats exposed to hypoxia of the same degree and duration but with normal NaCl intake. The parallel reduction in hypoxic hypertrophy of the right ventricle in NaCl-loaded rats could be considered as indirect evidence supporting the view that renin may be involved in the development of heart hypertrophy."} {"id": "PMID:159703", "title": "Diamide inhibited (Ca++ + Mg++) and (Mg++) dependent ATPase in erythrocyte membranes: activity at different temperatures.", "content": "After inhibition of the monovalent cation dependent ATPase, a (Ca++ + Mg++) and a (Mg++) dependent ATPase activity can be detected. The inhibition due to diamide on the (Mg++) ATPase, assayed in the 12.5 degrees C - 30 degrees C temperature range, is almost complete. On the contrary the diamide induced inhibition of (Ca++ + Mg++) ATPase, in the same temperature range, is not complete and the residual activity increases with temperature. The reported data indicate that the ATPase activity induced by calcium is much less diamide-sensitive and -SH-dependent than that elicited by Mg++ alone.", "contents": "Diamide inhibited (Ca++ + Mg++) and (Mg++) dependent ATPase in erythrocyte membranes: activity at different temperatures. After inhibition of the monovalent cation dependent ATPase, a (Ca++ + Mg++) and a (Mg++) dependent ATPase activity can be detected. The inhibition due to diamide on the (Mg++) ATPase, assayed in the 12.5 degrees C - 30 degrees C temperature range, is almost complete. On the contrary the diamide induced inhibition of (Ca++ + Mg++) ATPase, in the same temperature range, is not complete and the residual activity increases with temperature. The reported data indicate that the ATPase activity induced by calcium is much less diamide-sensitive and -SH-dependent than that elicited by Mg++ alone."} {"id": "PMID:159706", "title": "Effect of different flow patterns on the Wright respirometer.", "content": "The problems of using the Wright respirometer for measurements at small rates of flow associated with small volumes are discussed. Accuracy is very dependent on the wave form of the flow passing through it.", "contents": "Effect of different flow patterns on the Wright respirometer. The problems of using the Wright respirometer for measurements at small rates of flow associated with small volumes are discussed. Accuracy is very dependent on the wave form of the flow passing through it."} {"id": "PMID:159709", "title": "Local responses in primary and secondary human lung cancers. I. Patterns of cellular (eosinophils and macrophages) and extracellular (acid mucopolysaccharide) reactions.", "content": "Local free cell (eosinophils and macrophages) and extracellular (acid mucopolysaccharides) reactions were studied by histochemical techniques in 72 primary lung cancers (Group A), 17 pulmonary metastases and 5 lung tumours of unknown origin (Group B). Strong cellular reactions were more frequent in Group A than in Group B, whereas extracellular reactions were more frequent in Group B than in Group A. In both groups the degrees of eosinophilic infiltration and accumulation of acid mucopolysaccharides tended to be negatively correlated. In contrast, macrophages and eosinophils showed a positive correlation in the primary cancers, but none in the other tumours. The extracellular material had physical and chemical properties (solubility, affinity to stains and degradability by enzymes) of the sulphated acid mucopolysaccharides. From its distribution it appeared to be derived from fibroblasts and/or tumour cells.", "contents": "Local responses in primary and secondary human lung cancers. I. Patterns of cellular (eosinophils and macrophages) and extracellular (acid mucopolysaccharide) reactions. Local free cell (eosinophils and macrophages) and extracellular (acid mucopolysaccharides) reactions were studied by histochemical techniques in 72 primary lung cancers (Group A), 17 pulmonary metastases and 5 lung tumours of unknown origin (Group B). Strong cellular reactions were more frequent in Group A than in Group B, whereas extracellular reactions were more frequent in Group B than in Group A. In both groups the degrees of eosinophilic infiltration and accumulation of acid mucopolysaccharides tended to be negatively correlated. In contrast, macrophages and eosinophils showed a positive correlation in the primary cancers, but none in the other tumours. The extracellular material had physical and chemical properties (solubility, affinity to stains and degradability by enzymes) of the sulphated acid mucopolysaccharides. From its distribution it appeared to be derived from fibroblasts and/or tumour cells."} {"id": "PMID:159710", "title": "Local responses in primary and secondary human lung cancers. II. Clinical correlations.", "content": "Local infiltrates of eosinophilic leucocytes and macrophages and the deposition of acid mucopolysaccharides (AMPS) in 72 operable primary lung cancers and 17 isolated pulmonary metastases of known origin were correlated to tumour stage (radically or non-radically operable) and clinical course, by following the patients for 2-3 1/2 years. Half of the primary lung cancers showed strong local eosinophilia which, in combination with either strong macrophage infiltration or absence of AMPS reaction, characterized a very good prognosis in radically operable patients. No eosinophils, together with a strong AMPS reaction, indicated a very poor prognosis, irrespective of tumour stage. 16/17 metastases (7 different histologies) had either no local eosinophilia (13), strong AMPS deposition (12) or both (9). This suggests that malignant clones with great metastatic potential in general are characterized by absence of local eosinophilia and/or a strong AMPS reaction. These observations taken together indicate that local eosinophilia expresses an immune reaction which is, houl metastatic clones. It if does, metastatic success may be due to an escape mechanism based on the elaboration of AMPS.", "contents": "Local responses in primary and secondary human lung cancers. II. Clinical correlations. Local infiltrates of eosinophilic leucocytes and macrophages and the deposition of acid mucopolysaccharides (AMPS) in 72 operable primary lung cancers and 17 isolated pulmonary metastases of known origin were correlated to tumour stage (radically or non-radically operable) and clinical course, by following the patients for 2-3 1/2 years. Half of the primary lung cancers showed strong local eosinophilia which, in combination with either strong macrophage infiltration or absence of AMPS reaction, characterized a very good prognosis in radically operable patients. No eosinophils, together with a strong AMPS reaction, indicated a very poor prognosis, irrespective of tumour stage. 16/17 metastases (7 different histologies) had either no local eosinophilia (13), strong AMPS deposition (12) or both (9). This suggests that malignant clones with great metastatic potential in general are characterized by absence of local eosinophilia and/or a strong AMPS reaction. These observations taken together indicate that local eosinophilia expresses an immune reaction which is, houl metastatic clones. It if does, metastatic success may be due to an escape mechanism based on the elaboration of AMPS."} {"id": "PMID:159711", "title": "Perioral dermatitis: a 12-year review.", "content": "A continuing study of perioral dermatitis over a period of 12 years is presented. A distinction is made between various patterns of circumoral and paranasal dermatitis and the clinical picture that we describe as \"perioral dermatitis\". No cases were seen before 1966 but the number of patients presenting to hospital clinics or in private practice rose dramatically until 1970-1972, after which there has been a progressive fall in numbers. In this period, 259 patients were diagnosed as having the condition and of these 203, resident in an area of some 275,000 population and seen by one or other of us on at least two occasions, form the basis of this study. There were 173 females, fifteen males and fifteen children under 12 years of age. In many cases it was possible to suggest the primary lesion for which patients sought treatment. In sixty-nine patients this consisted of a para-oral eruption on the side of the chin and, in forty-one a paranasal erythematous dermatitis. The characteristic appearance and spread of the eruption to the glabella and eyelids are described. A few patients, mostly male, showed lesions around the eyelids only, from treatment of seborrhoeic dermatitis. All but nine of the patients acknowledged the use of potent (not necessarily fluorinated) topical corticosteroids over long periods; in many cases these were self-administered. Some of the children had been treated with preparations intended for their mothers. The numerous aetiological agents that have been incriminated as causes of this eruption are examined. We believe that the prolonged use of topical potent corticosteroids is the only one tenable from our observations. The role of hormonal factors and of local irritant agetns is examined in this context. Tetracyclines are curative in the great majority of patients in 6 weeks if local corticosteroids are discarded. Relapses are rare. Perioral dermatitis is a most satisfying condition to treat but several questions remain unanswered. The current \"revolt\" against all forms of cortisone may enable us to answer some of these in the near future.", "contents": "Perioral dermatitis: a 12-year review. A continuing study of perioral dermatitis over a period of 12 years is presented. A distinction is made between various patterns of circumoral and paranasal dermatitis and the clinical picture that we describe as \"perioral dermatitis\". No cases were seen before 1966 but the number of patients presenting to hospital clinics or in private practice rose dramatically until 1970-1972, after which there has been a progressive fall in numbers. In this period, 259 patients were diagnosed as having the condition and of these 203, resident in an area of some 275,000 population and seen by one or other of us on at least two occasions, form the basis of this study. There were 173 females, fifteen males and fifteen children under 12 years of age. In many cases it was possible to suggest the primary lesion for which patients sought treatment. In sixty-nine patients this consisted of a para-oral eruption on the side of the chin and, in forty-one a paranasal erythematous dermatitis. The characteristic appearance and spread of the eruption to the glabella and eyelids are described. A few patients, mostly male, showed lesions around the eyelids only, from treatment of seborrhoeic dermatitis. All but nine of the patients acknowledged the use of potent (not necessarily fluorinated) topical corticosteroids over long periods; in many cases these were self-administered. Some of the children had been treated with preparations intended for their mothers. The numerous aetiological agents that have been incriminated as causes of this eruption are examined. We believe that the prolonged use of topical potent corticosteroids is the only one tenable from our observations. The role of hormonal factors and of local irritant agetns is examined in this context. Tetracyclines are curative in the great majority of patients in 6 weeks if local corticosteroids are discarded. Relapses are rare. Perioral dermatitis is a most satisfying condition to treat but several questions remain unanswered. The current \"revolt\" against all forms of cortisone may enable us to answer some of these in the near future."} {"id": "PMID:159712", "title": "Perioral dermatitis.", "content": "Forty-three patients with perioral dermatitis are described. In seven patients, this eruption was associated with the use of hydrocortisone butyrate (Locoid) alone, and this topical steroid can no longer be recommended unreservedly for use on the face. In fifteen other patients, medication was undertaken without medical advice. The time may have come to print on tubes of potent local steroids warnings about the hazards of long-term use on the face without medical advice. Drug companies and pharmacists could also help by asking patients to discard any partially-used tubes of ointment and an expiry date stamped prominently on the tubes rather than on the cardboard container may help. Continuing medical education is obviously still required to prevent a minority of family doctors prescribing wrongly for their patients.", "contents": "Perioral dermatitis. Forty-three patients with perioral dermatitis are described. In seven patients, this eruption was associated with the use of hydrocortisone butyrate (Locoid) alone, and this topical steroid can no longer be recommended unreservedly for use on the face. In fifteen other patients, medication was undertaken without medical advice. The time may have come to print on tubes of potent local steroids warnings about the hazards of long-term use on the face without medical advice. Drug companies and pharmacists could also help by asking patients to discard any partially-used tubes of ointment and an expiry date stamped prominently on the tubes rather than on the cardboard container may help. Continuing medical education is obviously still required to prevent a minority of family doctors prescribing wrongly for their patients."} {"id": "PMID:159713", "title": "Activation of complement-a mechanism for the inflammation in acne.", "content": "An immunofluorescence investigation of thirty-six non-inflamed and thirty-four inflamed acne lesions has been carried out. Fluorescence for C3, unaccompanied by fluorescence for immunoglobulins, was found in the walls of dermal blood vessels or at the basement membrane zone of the comedo or at both these sites in fifty-seven lesions. Fluorescence for C3 accompanied by fluorescence for immunoglobulins was found in nine lesions. In two papules and three nodules the comedo was surrounded or replaced by a mononuclear cell infiltrate. These findings have been taken to indicate that cellular immune mechanisms are a late event and activation of complement is an early event in the pathogenesis of inflammation in acne. The mechanism of complement activation remains uncertain.", "contents": "Activation of complement-a mechanism for the inflammation in acne. An immunofluorescence investigation of thirty-six non-inflamed and thirty-four inflamed acne lesions has been carried out. Fluorescence for C3, unaccompanied by fluorescence for immunoglobulins, was found in the walls of dermal blood vessels or at the basement membrane zone of the comedo or at both these sites in fifty-seven lesions. Fluorescence for C3 accompanied by fluorescence for immunoglobulins was found in nine lesions. In two papules and three nodules the comedo was surrounded or replaced by a mononuclear cell infiltrate. These findings have been taken to indicate that cellular immune mechanisms are a late event and activation of complement is an early event in the pathogenesis of inflammation in acne. The mechanism of complement activation remains uncertain."} {"id": "PMID:159714", "title": "A double-blind trial of a zinc sulphate/citrate complex and tetracycline in the treatment of acne vulgaris.", "content": "Forty-eight patients participated in a 3-month double-blind study to compare the effect of orally administered zinc sulphate/citrate complex and tetracycline hydrochloride in acne vulgaris. Tetracycline significantly reduced the overall grade, and the number of non-inflamed lesions, papules and pustules by the third month. It also reduced significantly the non-inflamed lesions and papules at the end of the second month. In contrast, zinc therapy only had a significant effect on the pustules at the third month. The results indicate that tetracycline is far superior to the zinc complex in patients with moderately severe acne.", "contents": "A double-blind trial of a zinc sulphate/citrate complex and tetracycline in the treatment of acne vulgaris. Forty-eight patients participated in a 3-month double-blind study to compare the effect of orally administered zinc sulphate/citrate complex and tetracycline hydrochloride in acne vulgaris. Tetracycline significantly reduced the overall grade, and the number of non-inflamed lesions, papules and pustules by the third month. It also reduced significantly the non-inflamed lesions and papules at the end of the second month. In contrast, zinc therapy only had a significant effect on the pustules at the third month. The results indicate that tetracycline is far superior to the zinc complex in patients with moderately severe acne."} {"id": "PMID:159717", "title": "Bowenoid transformation of seborrhoeic verrucae (keratoses).", "content": "Seborrhoeic verrucae (keratoses) are considered to be benign lesions. Occasional bowenoid transformation of these benign growths has not been widely recognized. Seven cases of seborrhoeic verrucae with bowenoid transformations are presented to alert the clinician and the pathologist to this occurrence.", "contents": "Bowenoid transformation of seborrhoeic verrucae (keratoses). Seborrhoeic verrucae (keratoses) are considered to be benign lesions. Occasional bowenoid transformation of these benign growths has not been widely recognized. Seven cases of seborrhoeic verrucae with bowenoid transformations are presented to alert the clinician and the pathologist to this occurrence."} {"id": "PMID:159718", "title": "The Pearson Report--compromise or step towards effective and just compensation for disability?", "content": "The setting up of the Royal Commission on Civil Liability and Compensation for Personal Injury, its terms of reference and report are discussed. The main recommendations are detailed with brief consideration of their possible impact. The proposals are assessed and the philosophy and principles behind the reform, explicit or implicit in the Report, are considered. Finally, the extent to which the proposals can be a blueprint for later reforms dealing with compensation for disability in general is discussed.", "contents": "The Pearson Report--compromise or step towards effective and just compensation for disability? The setting up of the Royal Commission on Civil Liability and Compensation for Personal Injury, its terms of reference and report are discussed. The main recommendations are detailed with brief consideration of their possible impact. The proposals are assessed and the philosophy and principles behind the reform, explicit or implicit in the Report, are considered. Finally, the extent to which the proposals can be a blueprint for later reforms dealing with compensation for disability in general is discussed."} {"id": "PMID:159720", "title": "Conformation and activity of chloroplast coupling factor exposed to low chemical potential of water in cells.", "content": "(1) Photophosphorylation, Ca2+-ATPase and Mg2+-ATPase activities of isolated chloroplasts were inhibited 55--65% when the chemical potential of water was decreased by dehydrating leaves to water potentials (psi w) of --25 bars before isolation of the plastids. The inhibition could be reversed in vivo by rehydrating the leaves. (2) These losses in activity were reflected in coupling factor (CF1) isolated from the leaves, since CF1 from leaves with low psi w had less Ca2+-ATPase activity than control CF1 and did not recouple phosphorylation in CF1-deficient chloroplasts. In contrast, CF1 from leaves having high psi w only partially recoupled phosphorylation by CF1-deficient chloroplasts from leaves havig low psi w. This indicated that low psi w affected chloroplast membranes as well as CF1 itself. (3) Coupling factor from leaves having low psi w had the same number of subunits, and the same electrophoretic mobility, and could be obtained with the same yields as CF1 from control leaves. However, direct measurements of fluorescence polarization, ultraviolet absorption, and circular dichroism showed that CF1 from leaves having low psi w differed from control CF1. The CF1 from leaves having low psi w also had decreased ability to bind fluorescent nucleotides (epsilon-ATP and epsilon-ADP). (4) Exposure of isolated CF1 to low psi w in vitro by preincubation in sucrose-containing media inhibited the Ca2+-ATPase activity of the protein in subsequent assays without sucrose. Inclusion of 5 or 10 mM Mg2+ in the preincubation medium markedly inhibited Ca2+-ATPase activity. (5) These results show that CF1 undergoes changes in cells which alter its phosphorylating ability. Since low cell psi w changed the spectroscopic properties but not other protein properties of CF1, the changes were most likely caused by altered confurn, photophosphorylation. The inhibition of ATPase activity in CF1 in vitro at low psi w and high ion concentration mimicked the change in activity seen in vivo.", "contents": "Conformation and activity of chloroplast coupling factor exposed to low chemical potential of water in cells. (1) Photophosphorylation, Ca2+-ATPase and Mg2+-ATPase activities of isolated chloroplasts were inhibited 55--65% when the chemical potential of water was decreased by dehydrating leaves to water potentials (psi w) of --25 bars before isolation of the plastids. The inhibition could be reversed in vivo by rehydrating the leaves. (2) These losses in activity were reflected in coupling factor (CF1) isolated from the leaves, since CF1 from leaves with low psi w had less Ca2+-ATPase activity than control CF1 and did not recouple phosphorylation in CF1-deficient chloroplasts. In contrast, CF1 from leaves having high psi w only partially recoupled phosphorylation by CF1-deficient chloroplasts from leaves havig low psi w. This indicated that low psi w affected chloroplast membranes as well as CF1 itself. (3) Coupling factor from leaves having low psi w had the same number of subunits, and the same electrophoretic mobility, and could be obtained with the same yields as CF1 from control leaves. However, direct measurements of fluorescence polarization, ultraviolet absorption, and circular dichroism showed that CF1 from leaves having low psi w differed from control CF1. The CF1 from leaves having low psi w also had decreased ability to bind fluorescent nucleotides (epsilon-ATP and epsilon-ADP). (4) Exposure of isolated CF1 to low psi w in vitro by preincubation in sucrose-containing media inhibited the Ca2+-ATPase activity of the protein in subsequent assays without sucrose. Inclusion of 5 or 10 mM Mg2+ in the preincubation medium markedly inhibited Ca2+-ATPase activity. (5) These results show that CF1 undergoes changes in cells which alter its phosphorylating ability. Since low cell psi w changed the spectroscopic properties but not other protein properties of CF1, the changes were most likely caused by altered confurn, photophosphorylation. The inhibition of ATPase activity in CF1 in vitro at low psi w and high ion concentration mimicked the change in activity seen in vivo."} {"id": "PMID:159721", "title": "Stimulatory and inhibitory effects of dimethylsulfoxide, propranolol and chlorpromazine on the partial reactions of ATPase of sarcoplasmic reticulum.", "content": "The effects of dimethylsulfoxide, propranolol and chlorpromazine on the partial reactions of the ATPase of sarcoplasmic reticulum were investigated. When analyzed according to a reaction scheme in which the ADP-sensitive (E1P) and ADP-insensitive (E2P) phosphoenzymes occur sequentially and P1 is derived from the latter, dimethylsulfoxide decreased the rate of E2P hydrolysis whereas it stimulated the rate of the E1P to E2P conversion. Propranolol increased the rate of E2P hydrolysis while it decreased the rate of the E1P to E2P conversion. Propranolol exerted an additional effect, presumably inhibition of the phosphoenzyme formation. These effects of dimethylsulfoxide and propranolol can account for both the stimulatory and inhibitory effects of these drugs on the overall rate of ATP hydrolysis observed in the presence and absence of added alkali metal salts. Chlorpromazine accelerated E2P hydrolysis whereas it appeared to inhibit the E1P to E2P conversion. These effects of chlorpromazine appear able to account for its stimulatory and inhibitory effects on the overall rate of ATP hydrolysis in the presence and absence of alkali metal salts. In the presence of chlorpromazine, however, the rate of Pi liberation during the steady state ATP hydrolysis was found to be greater than the hydrolysis rate of E2P. This finding suggests that under these conditions Pi is derived not only from E2P but also from source(s) other than E2P.", "contents": "Stimulatory and inhibitory effects of dimethylsulfoxide, propranolol and chlorpromazine on the partial reactions of ATPase of sarcoplasmic reticulum. The effects of dimethylsulfoxide, propranolol and chlorpromazine on the partial reactions of the ATPase of sarcoplasmic reticulum were investigated. When analyzed according to a reaction scheme in which the ADP-sensitive (E1P) and ADP-insensitive (E2P) phosphoenzymes occur sequentially and P1 is derived from the latter, dimethylsulfoxide decreased the rate of E2P hydrolysis whereas it stimulated the rate of the E1P to E2P conversion. Propranolol increased the rate of E2P hydrolysis while it decreased the rate of the E1P to E2P conversion. Propranolol exerted an additional effect, presumably inhibition of the phosphoenzyme formation. These effects of dimethylsulfoxide and propranolol can account for both the stimulatory and inhibitory effects of these drugs on the overall rate of ATP hydrolysis observed in the presence and absence of added alkali metal salts. Chlorpromazine accelerated E2P hydrolysis whereas it appeared to inhibit the E1P to E2P conversion. These effects of chlorpromazine appear able to account for its stimulatory and inhibitory effects on the overall rate of ATP hydrolysis in the presence and absence of alkali metal salts. In the presence of chlorpromazine, however, the rate of Pi liberation during the steady state ATP hydrolysis was found to be greater than the hydrolysis rate of E2P. This finding suggests that under these conditions Pi is derived not only from E2P but also from source(s) other than E2P."} {"id": "PMID:159722", "title": "A Ca2+-stimulated ATPase activity in rabbit neutrophil membranes.", "content": "An ATPase activity specifically stimulated by micromolar Ca2+ concentrations has been identified in association with rabbit neurophil membranes. These studies provide the basis of further characterization of the Ca2+-ATPase activity with regard to neutrophil function.", "contents": "A Ca2+-stimulated ATPase activity in rabbit neutrophil membranes. An ATPase activity specifically stimulated by micromolar Ca2+ concentrations has been identified in association with rabbit neurophil membranes. These studies provide the basis of further characterization of the Ca2+-ATPase activity with regard to neutrophil function."} {"id": "PMID:159723", "title": "Chitin synthase activity from the slime variant of Neurospora crassa.", "content": "Chitin synthase (UDP-2-acetamido-2-deoxy-D-glucose:chitin 4-beta-acetamidodeoxy-D-glucosyltransferase, EC 2.4.1.16) activity from the wall-less variant of Neurospora crassa (slime) was partially characterized. The slime enzyme activity was found to be similar to that reported for slime-like and wild-type chitin synthase activities with respect to the following: specific activity, particulate cell-fraction localization, activation by N-acetylglucosamine, apparent Km with respect to substrate, pH optimum and ion requirement. It appears that the phenotype of slime cannot be solely accounted for by the absence of chitin synthase enzyme activity.", "contents": "Chitin synthase activity from the slime variant of Neurospora crassa. Chitin synthase (UDP-2-acetamido-2-deoxy-D-glucose:chitin 4-beta-acetamidodeoxy-D-glucosyltransferase, EC 2.4.1.16) activity from the wall-less variant of Neurospora crassa (slime) was partially characterized. The slime enzyme activity was found to be similar to that reported for slime-like and wild-type chitin synthase activities with respect to the following: specific activity, particulate cell-fraction localization, activation by N-acetylglucosamine, apparent Km with respect to substrate, pH optimum and ion requirement. It appears that the phenotype of slime cannot be solely accounted for by the absence of chitin synthase enzyme activity."} {"id": "PMID:159724", "title": "Metabolism of [17-2H]pregnenolone into 5-[17 beta-2H, 17 alpha-18O]androstene-3 beta, 17 alpha-diol and other products by incubation with the microsomal fraction of boar testis under 18O2 atmosphere.", "content": "[17-2H]Pregnenolone was incubated with the microsomal fraction of boar testis under an 18O2 atmosphere. The metabolites were analyzed by gas chromatography-mass spectrometry, and the following six metabolites labeled with 2H or 18O (or both) were identified: 17 alpha-[17-18O]hydroxypregnenolone, [17-18O]dehydroepiandrosterone, 5-[17-18O]androstene-3 beta, 17 beta-diol, 16 alpha-[16-18O]hydroxy[17-2H]pregnenolone, 5-[17 beta-2H, 17-18O]androstene-3 beta,17 alpha-diol, and 5,16-[17-2H]androstadien-3 beta-ol. The time course of the formation of these metabolites from pregnenolone was also studied using 14C-labeled substrate. The results obtained from these experiments suggest that the first three metabolites were synthesized by a well-documented pathway--pregnenolone yields 17 alpha-hydroxypregnenolone yields dehydroepiandrosterone yields 5-androstene-3 beta,17 beta-diol--, and that 16 alpha-hydroxypregnenolone, 5-androstene-3 beta,17 alpha-diol and 5,16-androstadien-3 beta-ol were synthesized from [17-2H]pregnenolone with retention of 17-2H.", "contents": "Metabolism of [17-2H]pregnenolone into 5-[17 beta-2H, 17 alpha-18O]androstene-3 beta, 17 alpha-diol and other products by incubation with the microsomal fraction of boar testis under 18O2 atmosphere. [17-2H]Pregnenolone was incubated with the microsomal fraction of boar testis under an 18O2 atmosphere. The metabolites were analyzed by gas chromatography-mass spectrometry, and the following six metabolites labeled with 2H or 18O (or both) were identified: 17 alpha-[17-18O]hydroxypregnenolone, [17-18O]dehydroepiandrosterone, 5-[17-18O]androstene-3 beta, 17 beta-diol, 16 alpha-[16-18O]hydroxy[17-2H]pregnenolone, 5-[17 beta-2H, 17-18O]androstene-3 beta,17 alpha-diol, and 5,16-[17-2H]androstadien-3 beta-ol. The time course of the formation of these metabolites from pregnenolone was also studied using 14C-labeled substrate. The results obtained from these experiments suggest that the first three metabolites were synthesized by a well-documented pathway--pregnenolone yields 17 alpha-hydroxypregnenolone yields dehydroepiandrosterone yields 5-androstene-3 beta,17 beta-diol--, and that 16 alpha-hydroxypregnenolone, 5-androstene-3 beta,17 alpha-diol and 5,16-androstadien-3 beta-ol were synthesized from [17-2H]pregnenolone with retention of 17-2H."} {"id": "PMID:159728", "title": "[Uptake of (14C) leucine and protein synthesis in potato tuber buds and effect of abscisic acid on these processes].", "content": "The uptake of [14C] leucine and its incorporation into proteins of dormant and growing potato tuber buds were studied. It was found that the label uptake was increased at the beginning of the growth period, whereas the dynamics of this process were not changed in comparison with the dormant buds samples. The rate of [14C] leucine incorporation into proteins was increased in the growing buds; this increase was not, however, due to the increase in the uptake of the labelled precursor and was probably caused by activation of the protein synthesis. In contrast, the activation of protein synthesis was accompanied by changses is the dynamic incorporation of [14C] leucine into the protein at the end of dormancy. The effect of abscisic acid (10(-7) M) on the protein synthesis was not connected with its action of the uptake of labelled precursor and depended on the physiological state of buds and incubation time. A possible mechanism of regulatory effect of abscisic acid on protein synthesis in potato tuber buds is discussed.", "contents": "[Uptake of (14C) leucine and protein synthesis in potato tuber buds and effect of abscisic acid on these processes]. The uptake of [14C] leucine and its incorporation into proteins of dormant and growing potato tuber buds were studied. It was found that the label uptake was increased at the beginning of the growth period, whereas the dynamics of this process were not changed in comparison with the dormant buds samples. The rate of [14C] leucine incorporation into proteins was increased in the growing buds; this increase was not, however, due to the increase in the uptake of the labelled precursor and was probably caused by activation of the protein synthesis. In contrast, the activation of protein synthesis was accompanied by changses is the dynamic incorporation of [14C] leucine into the protein at the end of dormancy. The effect of abscisic acid (10(-7) M) on the protein synthesis was not connected with its action of the uptake of labelled precursor and depended on the physiological state of buds and incubation time. A possible mechanism of regulatory effect of abscisic acid on protein synthesis in potato tuber buds is discussed."} {"id": "PMID:159727", "title": "A possible partitioning of segmental muscle stretch reflex into incompletely de-coupled parallel loops.", "content": "Based on previous investigations on focused signal transmission through the muscle stretch reflex system, a model is presented suggesting that different muscle areas (especially in large complex muscles such as the triceps surae muscle) may be regulated rather independently with respect to certain internal state variables, particularly internal length. Since the parallel localized reflex loops necessary for such local control tasks are inevitably coupled peripherally through the muscle and connective tissues, compensatory de-coupling elements would be required to reestablish at least partial independence. Whether and how this can be achieved at the level of spinal neuronal circuitry is investigated in connection with a discussion of the advantages of partially de-coupled reflex loops.", "contents": "A possible partitioning of segmental muscle stretch reflex into incompletely de-coupled parallel loops. Based on previous investigations on focused signal transmission through the muscle stretch reflex system, a model is presented suggesting that different muscle areas (especially in large complex muscles such as the triceps surae muscle) may be regulated rather independently with respect to certain internal state variables, particularly internal length. Since the parallel localized reflex loops necessary for such local control tasks are inevitably coupled peripherally through the muscle and connective tissues, compensatory de-coupling elements would be required to reestablish at least partial independence. Whether and how this can be achieved at the level of spinal neuronal circuitry is investigated in connection with a discussion of the advantages of partially de-coupled reflex loops."} {"id": "PMID:159729", "title": "[Effect of thermostable protein kinase modulator on Mg, Ca-ATPase from nervous tissue].", "content": "Isoelectric focusing of a purified fraction of thermostable modulator of 3',5'-AMP-dependent protein kinase revealed five individual proteins, the main protein having an isoelectric point of 4,05. The molecular weight of this protein as determined by gel filtration is 8000--9000. The protein with a pI of 4,05 binds Ca2+ and in contrast to the original modulator inhibits the endogenous 3',5'-AMP-dependent phosphorylation of synaptic membranes. An addition of the original modulator fraction to the microsomes isolated from nervous tissue increases the Mg, Ca-ATPase activity and absorption of 45Ca. Neither the protein with a pI of 4,05 nor other individual proteins affect the activity of transport ATPase. The activating effect is partly restored after mixing of all the five subfractions. It is assumed that these proteins are aggregated by Ca2+ and change the activity of ATPase or membrane 3',5'-AMP-dependent protein kinase depending on the concentration of calcium ions.", "contents": "[Effect of thermostable protein kinase modulator on Mg, Ca-ATPase from nervous tissue]. Isoelectric focusing of a purified fraction of thermostable modulator of 3',5'-AMP-dependent protein kinase revealed five individual proteins, the main protein having an isoelectric point of 4,05. The molecular weight of this protein as determined by gel filtration is 8000--9000. The protein with a pI of 4,05 binds Ca2+ and in contrast to the original modulator inhibits the endogenous 3',5'-AMP-dependent phosphorylation of synaptic membranes. An addition of the original modulator fraction to the microsomes isolated from nervous tissue increases the Mg, Ca-ATPase activity and absorption of 45Ca. Neither the protein with a pI of 4,05 nor other individual proteins affect the activity of transport ATPase. The activating effect is partly restored after mixing of all the five subfractions. It is assumed that these proteins are aggregated by Ca2+ and change the activity of ATPase or membrane 3',5'-AMP-dependent protein kinase depending on the concentration of calcium ions."} {"id": "PMID:159725", "title": "[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration].", "content": "The boundaries of the cell vitality domain in the enzyme activity space are calculated on the basis of a mathematical model of erythrocyte glycolysis. The boundaries are determined by key metabolite concentrations. The results obtained are compared with experimental data related to erythrocytic enzymopathies. It is shown that theoretical boundary enzyme activities coincide with the activities of hexokinase and in some cases phosphofruktokinase in enzyme deficient erythrocytes.", "contents": "[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration]. The boundaries of the cell vitality domain in the enzyme activity space are calculated on the basis of a mathematical model of erythrocyte glycolysis. The boundaries are determined by key metabolite concentrations. The results obtained are compared with experimental data related to erythrocytic enzymopathies. It is shown that theoretical boundary enzyme activities coincide with the activities of hexokinase and in some cases phosphofruktokinase in enzyme deficient erythrocytes."} {"id": "PMID:159730", "title": "[Two forms of Ca2+-dependent ATPase from sarcoplasmic reticulum].", "content": "Two highly purified sarcoplasmic reticulum membrane fractiones differing in their sensitivities to the uncoupling action of caffeine were isolated from white skeletal muscles of the rabbit. The main protein component of both fractions is a catalytical polypeptide of Ca2+-dependent ATPase. Treatment of the caffeine-sensitive reticular fraction by trypsin or DTNB completely removes the effect of caffeine. It was found that similar effects on the caffeine-sensitive reticular fraction are exerted by bemegride, camphor, ethymizole and cordiamine. Isolation of Ca2+-dependent ATPase from both reticular fractions and reconstruction of Ca2+-transporting vesicles were carried out. Ca2+ transport by the vesicles enriched by ATPase from the caffeine-sensitive reticular fraction is uncoupled under the effect of caffeine; however, caffeine has no effect on the vesicles enriched by caffeine-insensitive reticular ATPase. The molecular weight of caffeine-sensitive and caffeine-insensitive ATPases determined in the presence of sedium dodecyl sulfate are found to be identical. Electrophoresis in the presence of digitonin revealed different electrophoretic behaviour of the two forms of ATPase.", "contents": "[Two forms of Ca2+-dependent ATPase from sarcoplasmic reticulum]. Two highly purified sarcoplasmic reticulum membrane fractiones differing in their sensitivities to the uncoupling action of caffeine were isolated from white skeletal muscles of the rabbit. The main protein component of both fractions is a catalytical polypeptide of Ca2+-dependent ATPase. Treatment of the caffeine-sensitive reticular fraction by trypsin or DTNB completely removes the effect of caffeine. It was found that similar effects on the caffeine-sensitive reticular fraction are exerted by bemegride, camphor, ethymizole and cordiamine. Isolation of Ca2+-dependent ATPase from both reticular fractions and reconstruction of Ca2+-transporting vesicles were carried out. Ca2+ transport by the vesicles enriched by ATPase from the caffeine-sensitive reticular fraction is uncoupled under the effect of caffeine; however, caffeine has no effect on the vesicles enriched by caffeine-insensitive reticular ATPase. The molecular weight of caffeine-sensitive and caffeine-insensitive ATPases determined in the presence of sedium dodecyl sulfate are found to be identical. Electrophoresis in the presence of digitonin revealed different electrophoretic behaviour of the two forms of ATPase."} {"id": "PMID:159731", "title": "[Interaction of platinum and palladium 5-sulfo-8-mercaptoquinoline complexes with sarcoplasmic reticulum Ca2+-dependent ATPase].", "content": "5-Sulfo-8-mercaptoquinoline complexes of platinum and palladium (complexes I and II) effectively inhibit Ca2+-dependent ATPase from sarcoplasmic reticulum. However, in contrast to K2PtCl4, K2PdCl4 and other previously investigated platinum and palladium complexes, they do not interact with the thiol groups of the enzyme. The inhibiting effects of complexes I and II are reversible and competitive with respect to ATP. In aqueous solutions complexes I and II decrease the fluorescence of tryptophane with a simultaneous shift in fluorescence towards the long-wave region. The same effect is exerted by the complexes on the fluorescence of tryptophane residues in Ca2+-dependent ATPase preparations. An addition of tryptophane to the enzyme preparations preincubated with complexes I and II partly restores the enzyme activity. It is assumed that the inhibiting effect of complexes I and II is due to their non-covalent interactions with the trytophane residues vicinal to the ATPase center.", "contents": "[Interaction of platinum and palladium 5-sulfo-8-mercaptoquinoline complexes with sarcoplasmic reticulum Ca2+-dependent ATPase]. 5-Sulfo-8-mercaptoquinoline complexes of platinum and palladium (complexes I and II) effectively inhibit Ca2+-dependent ATPase from sarcoplasmic reticulum. However, in contrast to K2PtCl4, K2PdCl4 and other previously investigated platinum and palladium complexes, they do not interact with the thiol groups of the enzyme. The inhibiting effects of complexes I and II are reversible and competitive with respect to ATP. In aqueous solutions complexes I and II decrease the fluorescence of tryptophane with a simultaneous shift in fluorescence towards the long-wave region. The same effect is exerted by the complexes on the fluorescence of tryptophane residues in Ca2+-dependent ATPase preparations. An addition of tryptophane to the enzyme preparations preincubated with complexes I and II partly restores the enzyme activity. It is assumed that the inhibiting effect of complexes I and II is due to their non-covalent interactions with the trytophane residues vicinal to the ATPase center."} {"id": "PMID:159733", "title": "Effects of rate of repetitive stimulus presentation on the visual evoked brain potentials of young adults with Down's syndrome.", "content": "Visual evoked brain potentials (VEP) to repeated stimuli of several interstimulus intervals (ISI) were recorded from young adults with Down's syndrome (DS). The following results were obtained: (i) An ISI effect previously observed in normals: VEP amplitudes increased with increase in ISI; some ISI effect on latency was also observed; (ii) VEP amplitudes of DS subjects were larger than VEP amplitudes of normals; (iii) VEP peak latencies of DS subjects were longer than VEP peak latencies obtained from normals; (iv) ISI had a more pronounced effect on VEP amplitudes of DS than normal subjects. These results are discussed with respect to CNS differences and issues of attention and information processing.", "contents": "Effects of rate of repetitive stimulus presentation on the visual evoked brain potentials of young adults with Down's syndrome. Visual evoked brain potentials (VEP) to repeated stimuli of several interstimulus intervals (ISI) were recorded from young adults with Down's syndrome (DS). The following results were obtained: (i) An ISI effect previously observed in normals: VEP amplitudes increased with increase in ISI; some ISI effect on latency was also observed; (ii) VEP amplitudes of DS subjects were larger than VEP amplitudes of normals; (iii) VEP peak latencies of DS subjects were longer than VEP peak latencies obtained from normals; (iv) ISI had a more pronounced effect on VEP amplitudes of DS than normal subjects. These results are discussed with respect to CNS differences and issues of attention and information processing."} {"id": "PMID:159737", "title": "Totally implantable directional Doppler flowmeters.", "content": "Two totally implantable Doppler blood flowmeters have been developed for the chronic measurement of deep-body flows; made possibly by two custom-integrated circuits. The CW and pulsed Doppler instruments are small (less than 2.5 cm3), use little power (less than 30 mW), and have excellent baseline stability. The pulsed Doppler flowmeter is applied principally when velocity-profile information or a nonencircling transducer assembly is required but where minimal restraint of the animal for inductive telemetry is permissible. Using a circumferential cuff, the CW Doppler flowmeter monitors Doppler data over a at least a 3-meter range by means of RF telemetry and produces a single velocity estimate. These instruments compliment each other and other telemetry systems by proving the researcher with alternatives for the long-term measurement of deep-body flow without percutaneous leads.", "contents": "Totally implantable directional Doppler flowmeters. Two totally implantable Doppler blood flowmeters have been developed for the chronic measurement of deep-body flows; made possibly by two custom-integrated circuits. The CW and pulsed Doppler instruments are small (less than 2.5 cm3), use little power (less than 30 mW), and have excellent baseline stability. The pulsed Doppler flowmeter is applied principally when velocity-profile information or a nonencircling transducer assembly is required but where minimal restraint of the animal for inductive telemetry is permissible. Using a circumferential cuff, the CW Doppler flowmeter monitors Doppler data over a at least a 3-meter range by means of RF telemetry and produces a single velocity estimate. These instruments compliment each other and other telemetry systems by proving the researcher with alternatives for the long-term measurement of deep-body flow without percutaneous leads."} {"id": "PMID:159738", "title": "Totally implantable dimension telemetry.", "content": "A totally implantable dimension telemetry system has been developed to instrument animals for chronic physiological research. Implantable signal processing electronics allow free-roaming animals with no percutaneous leads while retaining the long-term redproducibility of fixed implanted transducers. Two low-powered, custom-integrated circuits have been developed and assembled into an implantable package capable of measuring one dimension channel. The system has been operated in the amplitude modes of through-transmission and reflection as well as in a new Doppler-power configuration and aimed at determining interfaces between blood and surrounding structures. In a addition to single channel systems, these ICs are key elements in multimode, multidimensional implants capable of more accurate characterization of deep body structures.", "contents": "Totally implantable dimension telemetry. A totally implantable dimension telemetry system has been developed to instrument animals for chronic physiological research. Implantable signal processing electronics allow free-roaming animals with no percutaneous leads while retaining the long-term redproducibility of fixed implanted transducers. Two low-powered, custom-integrated circuits have been developed and assembled into an implantable package capable of measuring one dimension channel. The system has been operated in the amplitude modes of through-transmission and reflection as well as in a new Doppler-power configuration and aimed at determining interfaces between blood and surrounding structures. In a addition to single channel systems, these ICs are key elements in multimode, multidimensional implants capable of more accurate characterization of deep body structures."} {"id": "PMID:159739", "title": "An integrated circuit approach to totally implantable telemetry systems.", "content": "A series of totally implantable telemetry systems has been developed to determine such key physiological parameters as blood flow, pressure, dimensions, temperature, and bioelectrical activity in chronic research animals. Custom integrated circuits provide the signal-processing complexity and performance required to sufficiently instrument the animals for an accurate prediction of human responses. Additional implant and transducer technologies are necessary to complete the instrument package. Although the costs of these technologies are high, they are more than offset by the unique information obtained and overall reduction in the expenses of medical research because fewer animals can be studied over longer periods. A number of the IC-based implants are in use in several physiology and experimental drug studies where adequate reliability and performance could not be achieved by alternate approaches.", "contents": "An integrated circuit approach to totally implantable telemetry systems. A series of totally implantable telemetry systems has been developed to determine such key physiological parameters as blood flow, pressure, dimensions, temperature, and bioelectrical activity in chronic research animals. Custom integrated circuits provide the signal-processing complexity and performance required to sufficiently instrument the animals for an accurate prediction of human responses. Additional implant and transducer technologies are necessary to complete the instrument package. Although the costs of these technologies are high, they are more than offset by the unique information obtained and overall reduction in the expenses of medical research because fewer animals can be studied over longer periods. A number of the IC-based implants are in use in several physiology and experimental drug studies where adequate reliability and performance could not be achieved by alternate approaches."} {"id": "PMID:159742", "title": "The exceptional responsiveness of certain human myeloid leukemia cells to colony-stimulating activity.", "content": "We have studied the marrow cells from a patient with acute myeloid leukemia (AML) for their responsiveness to colony-stimulating activity (CSA) in vitro. The AML cells were stimulated by CSA to rapid and extended growth in liquid culture. In the absence of CSA, the majority of cells died. CSA also stimulated the clonal growth of AML cells, and the minimum requirement for CSA was one-tenth to one-fiftieth that required to stimulate the growth of normal marrow CFU-C. CSA for AML cells was eluted from Sephacryl S-200 columns in fractions that represented an apparent molecular weight of 45,000 daltons. This fraction also produced optimal stimulation of normal human marrow. During remission, the patient's marrow cells did not grow in liquid culture and produced normal numbers of granulocytic and erythroid colonies in response to CSA and erythropoietin. Extended culture of the AML cells resulted in cell differentiation evidenced by decreasing proliferative capacity and by morphological and histochemical changes. These studies indicate that certain AML cells are extraordinarily responsive to CSA, an in vitro mediator of normal granulopoiesis.", "contents": "The exceptional responsiveness of certain human myeloid leukemia cells to colony-stimulating activity. We have studied the marrow cells from a patient with acute myeloid leukemia (AML) for their responsiveness to colony-stimulating activity (CSA) in vitro. The AML cells were stimulated by CSA to rapid and extended growth in liquid culture. In the absence of CSA, the majority of cells died. CSA also stimulated the clonal growth of AML cells, and the minimum requirement for CSA was one-tenth to one-fiftieth that required to stimulate the growth of normal marrow CFU-C. CSA for AML cells was eluted from Sephacryl S-200 columns in fractions that represented an apparent molecular weight of 45,000 daltons. This fraction also produced optimal stimulation of normal human marrow. During remission, the patient's marrow cells did not grow in liquid culture and produced normal numbers of granulocytic and erythroid colonies in response to CSA and erythropoietin. Extended culture of the AML cells resulted in cell differentiation evidenced by decreasing proliferative capacity and by morphological and histochemical changes. These studies indicate that certain AML cells are extraordinarily responsive to CSA, an in vitro mediator of normal granulopoiesis."} {"id": "PMID:159746", "title": "Sensitivity of Neisseria gonorrhoeae to antibiotics in London (1976-78).", "content": "Three surveys of the sensitivity of pretreatment isolates of gonococci to penicillin, ampicillin, tetracycline, spectinomycin, streptomycin, and co-trimoxazole were carried out during the period 1976-78. Compared with the results of previous surveys in the London area the decline in the proportion of strains of gonococci which are insensitive to penicillin appears to have halted. No changes were found in the levels of resistance to ampicillin, tetracycline, or spectinomycin during the period surveyed, although there was a slight increase in the proportion of strains requiring concentrations of 20 microgram spectinomycin per ml for inhibition. Streptomycin resistance has decreased considerably and 91% of strains are now sensitive to 10 microgram streptomycin per ml.", "contents": "Sensitivity of Neisseria gonorrhoeae to antibiotics in London (1976-78). Three surveys of the sensitivity of pretreatment isolates of gonococci to penicillin, ampicillin, tetracycline, spectinomycin, streptomycin, and co-trimoxazole were carried out during the period 1976-78. Compared with the results of previous surveys in the London area the decline in the proportion of strains of gonococci which are insensitive to penicillin appears to have halted. No changes were found in the levels of resistance to ampicillin, tetracycline, or spectinomycin during the period surveyed, although there was a slight increase in the proportion of strains requiring concentrations of 20 microgram spectinomycin per ml for inhibition. Streptomycin resistance has decreased considerably and 91% of strains are now sensitive to 10 microgram streptomycin per ml."} {"id": "PMID:159743", "title": "[Left ventricular function in chronic obstructive lung disease (author's transl)].", "content": "Left ventricular function was studied at rest and during post-extrasystolic potentiation in 18 patients with chronic obstructive lung disease. The contractility indices used were obtained from pressures recorded in the isovolumetric period (left ventricular end-diastolic pressure, Vmax., VECmax., dP/dtmax.) and from volume variations during ejection (end-diastolic volume, ejection fraction, VCF). Left ventricular diastolic compliance was also evaluated. All patients were hypoxic (PaO2 = 58 +/- 7 torr); six of them had cor pulmonale (group B); the remaining 12 patients constituted group A. Left ventricular function of groups A and B was similar; we conclude that right cardiac failure, in cor pulmonale, is not secondary to left ventricular failure. However, left ventricular dysfunction exists; the left ventricle is hypertrophied (probably resulting from chronic hypoxia). Pump function is altered (abnormal ventricular function points are found), but left ventricular kinetics is normal or exaggerated (ejection fraction and VCF are increased). Isovolumetric phase contractility indices are diminished; however, they may increase normally during post-extrasystolic potentiation. Left ventricular compliance is abnormal due to left and right ventricular hypertrophy and to paradoxical movement of the interventricular septum which impedes diastolic expansion of the left ventricle. These changes are responsible for decreased left ventricular output. There seems to exist an impairment of left ventricular function related to both intrinsic (secondary to hypoxia, hypercapnia, left ventricular hypertrophy) and extrinsic factors (right ventricula hypertrophy deviating interventricular septum, lowering of left ventricular preload).", "contents": "[Left ventricular function in chronic obstructive lung disease (author's transl)]. Left ventricular function was studied at rest and during post-extrasystolic potentiation in 18 patients with chronic obstructive lung disease. The contractility indices used were obtained from pressures recorded in the isovolumetric period (left ventricular end-diastolic pressure, Vmax., VECmax., dP/dtmax.) and from volume variations during ejection (end-diastolic volume, ejection fraction, VCF). Left ventricular diastolic compliance was also evaluated. All patients were hypoxic (PaO2 = 58 +/- 7 torr); six of them had cor pulmonale (group B); the remaining 12 patients constituted group A. Left ventricular function of groups A and B was similar; we conclude that right cardiac failure, in cor pulmonale, is not secondary to left ventricular failure. However, left ventricular dysfunction exists; the left ventricle is hypertrophied (probably resulting from chronic hypoxia). Pump function is altered (abnormal ventricular function points are found), but left ventricular kinetics is normal or exaggerated (ejection fraction and VCF are increased). Isovolumetric phase contractility indices are diminished; however, they may increase normally during post-extrasystolic potentiation. Left ventricular compliance is abnormal due to left and right ventricular hypertrophy and to paradoxical movement of the interventricular septum which impedes diastolic expansion of the left ventricle. These changes are responsible for decreased left ventricular output. There seems to exist an impairment of left ventricular function related to both intrinsic (secondary to hypoxia, hypercapnia, left ventricular hypertrophy) and extrinsic factors (right ventricula hypertrophy deviating interventricular septum, lowering of left ventricular preload)."} {"id": "PMID:159749", "title": "[Increase of non-specific resistance to infection by synthetic adjuvants].", "content": "MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status.", "contents": "[Increase of non-specific resistance to infection by synthetic adjuvants]. MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status."} {"id": "PMID:159750", "title": "[Mechanism of action of T cell factors regulating antibody formation].", "content": "While the induction of antibody synthesis depends on antigen specific T cell factors, its magnitude is under control of non antigen specific T cell factors. In this respect, TRF (\"T cell Replacing Factor\") amplifies antibody responses while IBF (\"Immunoglobulin Binding Factor\") acts as a suppressor factor. Using cultures of spleen cells from nude mice, we show that both factors act sequentially, influencing the final differenciation of B cells to antibody producing cells. We have no evidence of direct interaction between TRF and IBF.", "contents": "[Mechanism of action of T cell factors regulating antibody formation]. While the induction of antibody synthesis depends on antigen specific T cell factors, its magnitude is under control of non antigen specific T cell factors. In this respect, TRF (\"T cell Replacing Factor\") amplifies antibody responses while IBF (\"Immunoglobulin Binding Factor\") acts as a suppressor factor. Using cultures of spleen cells from nude mice, we show that both factors act sequentially, influencing the final differenciation of B cells to antibody producing cells. We have no evidence of direct interaction between TRF and IBF."} {"id": "PMID:159751", "title": "[Macrophage receptors].", "content": "Macrophages are involved in many immunological functions such as phagocytosis, cytotoxicity, antigen binding and cooperation with lymphocytes. The triggering of those functions involves membrane receptors. Several receptors species are well characterized, but some phenomena can be accounted for only if macrophages are endowed with nonspecific adhesive structures. A study of the effect of various physical or chemical factors on the binding of several particle species by rat peritoneal macrophages allowed us to classify nonspecific receptors and discuss the mechanisms involved in some types of cellular interaction.", "contents": "[Macrophage receptors]. Macrophages are involved in many immunological functions such as phagocytosis, cytotoxicity, antigen binding and cooperation with lymphocytes. The triggering of those functions involves membrane receptors. Several receptors species are well characterized, but some phenomena can be accounted for only if macrophages are endowed with nonspecific adhesive structures. A study of the effect of various physical or chemical factors on the binding of several particle species by rat peritoneal macrophages allowed us to classify nonspecific receptors and discuss the mechanisms involved in some types of cellular interaction."} {"id": "PMID:159752", "title": "[Pharmacologic study of inflammatory processes. Modification of polynuclear neutrophil chemotaxis].", "content": "A study of rat polymorphonuclear chemotaxis has been made by a direct microscopic method and the effect of inflammatory reactions induced by carrageenan, calcium pyrophosphate and complete Freund's adjuvant has been studied. In addition the action of various drugs such as cholera toxin, colchicine, prostaglandins and certain immunomodulators, was investigated. The results have been analysed with special regard to the role of chemotaxis in inflammatory responses.", "contents": "[Pharmacologic study of inflammatory processes. Modification of polynuclear neutrophil chemotaxis]. A study of rat polymorphonuclear chemotaxis has been made by a direct microscopic method and the effect of inflammatory reactions induced by carrageenan, calcium pyrophosphate and complete Freund's adjuvant has been studied. In addition the action of various drugs such as cholera toxin, colchicine, prostaglandins and certain immunomodulators, was investigated. The results have been analysed with special regard to the role of chemotaxis in inflammatory responses."} {"id": "PMID:159753", "title": "[Cell mediated cytolysis: identification, enumeration and characterization of killer cells].", "content": "Killer cells responsible of the cell mediated cytolysis are identified by a microtechnique: effector cells are individually associated to target cells and incubated at 37 degrees C; killers are identified by their associated target lysis. Thus killer cells are enumerated in the effector cell suspensions. Furthermore, isolated killer can be characterized and their lethal action studied.", "contents": "[Cell mediated cytolysis: identification, enumeration and characterization of killer cells]. Killer cells responsible of the cell mediated cytolysis are identified by a microtechnique: effector cells are individually associated to target cells and incubated at 37 degrees C; killers are identified by their associated target lysis. Thus killer cells are enumerated in the effector cell suspensions. Furthermore, isolated killer can be characterized and their lethal action studied."} {"id": "PMID:159754", "title": "[Contribution of two-dimensional immunoelectrophoresis technics to the study of the structure and the morphogenesis of human adenovirus].", "content": "The two-dimensional immunoelectrophoresis has been applied to human adenovirus type-2 structural analysis. This method is both qualitative and quantitative and was used in the following studies. 1) Detection of major and minor capsid antigens. 2) Identification of viral antigenic components in the infected cell material. 3) Quantification of antigens and serological characterization of ts mutants. 4) Identification of polymeric forms of structural proteins. 5) Assembly analysis of capsid subunits. 6) Stoichiometric analysis of proteins within the virion. 7) Obtaining of monospecific sera.", "contents": "[Contribution of two-dimensional immunoelectrophoresis technics to the study of the structure and the morphogenesis of human adenovirus]. The two-dimensional immunoelectrophoresis has been applied to human adenovirus type-2 structural analysis. This method is both qualitative and quantitative and was used in the following studies. 1) Detection of major and minor capsid antigens. 2) Identification of viral antigenic components in the infected cell material. 3) Quantification of antigens and serological characterization of ts mutants. 4) Identification of polymeric forms of structural proteins. 5) Assembly analysis of capsid subunits. 6) Stoichiometric analysis of proteins within the virion. 7) Obtaining of monospecific sera."} {"id": "PMID:159755", "title": "[Sickle cell anemia and the affinity of the blood for oxygen].", "content": "Blood affinity for oxygen is reduced in patients with homozygous HbS disease. The mechanisms were related to polymerisation and sickling process. In the HbS blood, P50 values were related to the percentage of sickling, the effect of prior deoxygenation on P50 measurement was established. This work underlines the influences of experimental conditions on the determination of sickle cell blood affinity and the difficulties inherent in the evaluation of in vivo oxygen transport in sickle cell disease.", "contents": "[Sickle cell anemia and the affinity of the blood for oxygen]. Blood affinity for oxygen is reduced in patients with homozygous HbS disease. The mechanisms were related to polymerisation and sickling process. In the HbS blood, P50 values were related to the percentage of sickling, the effect of prior deoxygenation on P50 measurement was established. This work underlines the influences of experimental conditions on the determination of sickle cell blood affinity and the difficulties inherent in the evaluation of in vivo oxygen transport in sickle cell disease."} {"id": "PMID:159756", "title": "[Localization of binding sites in the hemoglobin-haptoglobin complex].", "content": "The binding and specific elution of Hb peptides from Hp was studied. Our results were confirmed by the study of inhibition of binding of alpha chains to Hp. In conclusion, a model of contact areas of Hp-Hb complex is proposed.", "contents": "[Localization of binding sites in the hemoglobin-haptoglobin complex]. The binding and specific elution of Hb peptides from Hp was studied. Our results were confirmed by the study of inhibition of binding of alpha chains to Hp. In conclusion, a model of contact areas of Hp-Hb complex is proposed."} {"id": "PMID:159757", "title": "[Non-enzymatic hemoglobin glycosylation in the normal and diabetic patient].", "content": "The criteria to be satisfied for a valid quantitation and the physiopathological significance of results: nature, site-specificity and kinetics of glycosylation, finally theoretical consideration of glycosylation of other proteins are the problems discussed.", "contents": "[Non-enzymatic hemoglobin glycosylation in the normal and diabetic patient]. The criteria to be satisfied for a valid quantitation and the physiopathological significance of results: nature, site-specificity and kinetics of glycosylation, finally theoretical consideration of glycosylation of other proteins are the problems discussed."} {"id": "PMID:159758", "title": "[Methods of tissue characterization with ultrasonic spectroscopy, analysis of the results obtained, prospects for clinical application in a short time].", "content": "So far, to account for ultrasonic attenuation in soft tissues molecular scale relaxation theory is retained. In addition to these mechanisms, the authors have obtained experimental evidence proving the role also plaid by cellular scale resonance mechanisms. Moreover, in addition to incoherent diffusion, it has been found that some tissues exhibit some coherent diffusion. All these experimental findings allows us to establish the feasability of non invasive ultrasonic biopsies.", "contents": "[Methods of tissue characterization with ultrasonic spectroscopy, analysis of the results obtained, prospects for clinical application in a short time]. So far, to account for ultrasonic attenuation in soft tissues molecular scale relaxation theory is retained. In addition to these mechanisms, the authors have obtained experimental evidence proving the role also plaid by cellular scale resonance mechanisms. Moreover, in addition to incoherent diffusion, it has been found that some tissues exhibit some coherent diffusion. All these experimental findings allows us to establish the feasability of non invasive ultrasonic biopsies."} {"id": "PMID:159760", "title": "[Clinical and biological forms of cytochrome b5 reductase deficiency].", "content": "Twenty-four personal cases of recessive congenital methemoglobinemia (RCM) due to cytochrome b5 reductase deficiency are analysed. They can be divided into two categories: 1) RCM type I, in which cyanosis is the single clinical symptom; 2) RCM type II in which cyanosis is associated with severe mental retardation and bilateral athetosis. The enzyme deficiency is restricted to the red cell soluble cytochrome b5 reductase in RCM type I, whereas in the type II form the enzyme defect is generalized to all tissues, involving both the soluble and the microsomal forms of cytochrome b5 reductase. Different mutations occurring at the same locus might account for this heterogeneity. However the mechanism of brain damage in case of generalized deficiency of cytochrome b5 reductase is still unknown.", "contents": "[Clinical and biological forms of cytochrome b5 reductase deficiency]. Twenty-four personal cases of recessive congenital methemoglobinemia (RCM) due to cytochrome b5 reductase deficiency are analysed. They can be divided into two categories: 1) RCM type I, in which cyanosis is the single clinical symptom; 2) RCM type II in which cyanosis is associated with severe mental retardation and bilateral athetosis. The enzyme deficiency is restricted to the red cell soluble cytochrome b5 reductase in RCM type I, whereas in the type II form the enzyme defect is generalized to all tissues, involving both the soluble and the microsomal forms of cytochrome b5 reductase. Different mutations occurring at the same locus might account for this heterogeneity. However the mechanism of brain damage in case of generalized deficiency of cytochrome b5 reductase is still unknown."} {"id": "PMID:159761", "title": "[Medical aspects of superoxide dismutases].", "content": "The role of superoxide radicals and of superoxide dismutases in inflammation is described. Encapsulation of the enzyme in liposomes leads to an increased organ specificity on injection into animals. Preliminary results of medical application are presented.", "contents": "[Medical aspects of superoxide dismutases]. The role of superoxide radicals and of superoxide dismutases in inflammation is described. Encapsulation of the enzyme in liposomes leads to an increased organ specificity on injection into animals. Preliminary results of medical application are presented."} {"id": "PMID:159762", "title": "[Ultrastructural study of cardiotoxicity and skin alterations in the golden hamster after treatment with 8 different anthracyclines].", "content": "Golden hamsters were submitted to i.p. administration during 4 weeks of 8 anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), adriamycin hydrochloride (ADMh), rubidazon (RBZ), aclacinomycin (ACM) and AD32, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. The comparative study of the mortality, the electron microscopic (EM) alterations of the myocardium, and the light microscopic (EM) alterations of the myocardium, and the light microscopic (LM) lesions of the skin, show that ACM and AD32 are the least toxic drugs. EM detected almost no early lesions of myocardium in ACM treated animals, but, after 4 week's treatment, severe cardiac alterations appeared which, like those after AD32 treatment, are non lethal and reversible. Similarly. LM revealed no histologic changes in the skin following ACM and AD32 administrations, but pathologic alterations, atrophy and alopecia, were observed in animals receiving all other drugs.", "contents": "[Ultrastructural study of cardiotoxicity and skin alterations in the golden hamster after treatment with 8 different anthracyclines]. Golden hamsters were submitted to i.p. administration during 4 weeks of 8 anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), adriamycin hydrochloride (ADMh), rubidazon (RBZ), aclacinomycin (ACM) and AD32, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. The comparative study of the mortality, the electron microscopic (EM) alterations of the myocardium, and the light microscopic (EM) alterations of the myocardium, and the light microscopic (LM) lesions of the skin, show that ACM and AD32 are the least toxic drugs. EM detected almost no early lesions of myocardium in ACM treated animals, but, after 4 week's treatment, severe cardiac alterations appeared which, like those after AD32 treatment, are non lethal and reversible. Similarly. LM revealed no histologic changes in the skin following ACM and AD32 administrations, but pathologic alterations, atrophy and alopecia, were observed in animals receiving all other drugs."} {"id": "PMID:159763", "title": "[Recent results in the field of vinblastine group antitumour alkaloids. Biochemical studies].", "content": "Studies on the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configuration at C14' and C16', as well as the presence of the methoxycarbonyl group on C16' seem to play an essential role in the determination of biological activity. A new analogue, detected by its specific behaviour with tubulin, was found, in vivo, to be as active and less toxic than vinblastine.", "contents": "[Recent results in the field of vinblastine group antitumour alkaloids. Biochemical studies]. Studies on the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configuration at C14' and C16', as well as the presence of the methoxycarbonyl group on C16' seem to play an essential role in the determination of biological activity. A new analogue, detected by its specific behaviour with tubulin, was found, in vivo, to be as active and less toxic than vinblastine."} {"id": "PMID:159764", "title": "[Recent data on the kidney tubule behavior of phosphorus, calcium and magnesium ions].", "content": "Information recently obtained about tubular renal handling of phosphorus calcium and magnesium ions deals with: 1. Localization of transport processes along the nephron; 2. Effects of several hormones on those transports, particularly parathyroid hormone and calcitonin, and localization of their receptor sites along the nephron; 3. Adaptation of phosphate tubular handling to its content in the diet; 4. Mechanisms of cellular transports.", "contents": "[Recent data on the kidney tubule behavior of phosphorus, calcium and magnesium ions]. Information recently obtained about tubular renal handling of phosphorus calcium and magnesium ions deals with: 1. Localization of transport processes along the nephron; 2. Effects of several hormones on those transports, particularly parathyroid hormone and calcitonin, and localization of their receptor sites along the nephron; 3. Adaptation of phosphate tubular handling to its content in the diet; 4. Mechanisms of cellular transports."} {"id": "PMID:159765", "title": "[Regulation of calcium metabolism ; its rhythmic variations].", "content": "In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy, were restored by feeding rats a high-calcium diet. A suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism.", "contents": "[Regulation of calcium metabolism ; its rhythmic variations]. In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy, were restored by feeding rats a high-calcium diet. A suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism."} {"id": "PMID:159766", "title": "[Experimental study of left ventricular assistance].", "content": "An experimental study, on normal dog and a model of cardiogenic shock, using an extracorporeal circuit including 2 cannulae and a centrifugal pump, has shown the superiority of the ventriculo-aortic bypass on the atrio-aortic bypass, for a complete left ventricular mechanical assistance.", "contents": "[Experimental study of left ventricular assistance]. An experimental study, on normal dog and a model of cardiogenic shock, using an extracorporeal circuit including 2 cannulae and a centrifugal pump, has shown the superiority of the ventriculo-aortic bypass on the atrio-aortic bypass, for a complete left ventricular mechanical assistance."} {"id": "PMID:159767", "title": "[Reactive metabolites of xenobiotics : their role in the hepatotoxicity of drugs].", "content": "Certain drugs are transformed into reactive metabolites by cytochrome P-450, a hepatic microsomal enzyme. The reactive metabolites covalently bind to hepatocyte macromolecules, thus determining liver lesions. Induction of microsomial enzymes increases the formation of reactive metabolites and exaggerates hepatotoxicity of these drugs.", "contents": "[Reactive metabolites of xenobiotics : their role in the hepatotoxicity of drugs]. Certain drugs are transformed into reactive metabolites by cytochrome P-450, a hepatic microsomal enzyme. The reactive metabolites covalently bind to hepatocyte macromolecules, thus determining liver lesions. Induction of microsomial enzymes increases the formation of reactive metabolites and exaggerates hepatotoxicity of these drugs."} {"id": "PMID:159768", "title": "[Hepatic tissue enzymes: study in cultures of rat liver epithelial cells. Control and analysis of cells by cytogenetic and mass spectrometric methods. Pharmacological applications].", "content": "Extensive studies of parameters conditioning selection and high plating efficiency of epithelial liver cells at primary seeding allowed us to set up a technique for the routine culture of liver cells from rats of various ages (18 day-old pc to 7 month-old) in Ham F10 medium supplemented with 10 p. cent fetal calf serum and 10 p. cent human serum. Cultures, after several passages, or sometimes at primary seeding were free of fibroblasts. The quality of water for culture medium preparation was found to be a very important parameter. G-banding caryotype showed that cells in culture were diploid until 15-20 passages. Various metabolic pathways have been studied in primary culture and in cell lines: enzymes of the anaerobic metabolism of hexoses and metabolism of steroid hormones and xenobiotics. Activity of glucose-6-phosphatase was nearly lost in all cultures. Activity of glucose-6-phosphatase was nearly lost in all cultures. Aldolase showed a specific liver activity with a cleavage ratio of phosphofructoses (F-1,6-diP/F-1-P) equal to 1 or about 1 in several primary cultures and cell lines. Many metabolites arising from incubation of cell lines with 14C-labelled corticosterone, corticosterone-21-sulfate, testosterone and progesterone have been isolated and quantitated by gas liquid chromatography (GC) and mass fragmentography coupled to GC, using 14C/12C isotope ratio measurements. These metabolites indicate the presence in cultured cells of 3 alpha/beta-steroid-reductases, 4-ene steroid reductases and hydroxylases at various positions: 2 alpha, 2 beta, 6 alpha, 6 beta, 7 alpha, 17 beta and 16 alpha. These cell lines were able to activate carcinogens through the epoxide-diol pathway and are suitable for drug metabolism study.", "contents": "[Hepatic tissue enzymes: study in cultures of rat liver epithelial cells. Control and analysis of cells by cytogenetic and mass spectrometric methods. Pharmacological applications]. Extensive studies of parameters conditioning selection and high plating efficiency of epithelial liver cells at primary seeding allowed us to set up a technique for the routine culture of liver cells from rats of various ages (18 day-old pc to 7 month-old) in Ham F10 medium supplemented with 10 p. cent fetal calf serum and 10 p. cent human serum. Cultures, after several passages, or sometimes at primary seeding were free of fibroblasts. The quality of water for culture medium preparation was found to be a very important parameter. G-banding caryotype showed that cells in culture were diploid until 15-20 passages. Various metabolic pathways have been studied in primary culture and in cell lines: enzymes of the anaerobic metabolism of hexoses and metabolism of steroid hormones and xenobiotics. Activity of glucose-6-phosphatase was nearly lost in all cultures. Activity of glucose-6-phosphatase was nearly lost in all cultures. Aldolase showed a specific liver activity with a cleavage ratio of phosphofructoses (F-1,6-diP/F-1-P) equal to 1 or about 1 in several primary cultures and cell lines. Many metabolites arising from incubation of cell lines with 14C-labelled corticosterone, corticosterone-21-sulfate, testosterone and progesterone have been isolated and quantitated by gas liquid chromatography (GC) and mass fragmentography coupled to GC, using 14C/12C isotope ratio measurements. These metabolites indicate the presence in cultured cells of 3 alpha/beta-steroid-reductases, 4-ene steroid reductases and hydroxylases at various positions: 2 alpha, 2 beta, 6 alpha, 6 beta, 7 alpha, 17 beta and 16 alpha. These cell lines were able to activate carcinogens through the epoxide-diol pathway and are suitable for drug metabolism study."} {"id": "PMID:159769", "title": "[Hypothalamic control of TSH secretion. Current methods of exploration and perspectives for the future].", "content": "The progress about the control by the pituitary gland of TSH secretion involves the clinical use of TRH test. However some TSH deficiencies are due to an hypothalamic disorder. A better knowledge about the aminergic regulation of the TRH secretion is necessary to design a new test exploring the hypothalamic structures which control TSH secretion.", "contents": "[Hypothalamic control of TSH secretion. Current methods of exploration and perspectives for the future]. The progress about the control by the pituitary gland of TSH secretion involves the clinical use of TRH test. However some TSH deficiencies are due to an hypothalamic disorder. A better knowledge about the aminergic regulation of the TRH secretion is necessary to design a new test exploring the hypothalamic structures which control TSH secretion."} {"id": "PMID:159770", "title": "[Value of 17-hydroxyprogesterone determination in exploration of adrenal cortex enzyme deficiencies].", "content": "17-hydroxyprogesterone (17-OH-P) was measured in various populations by radioimmunoassay, using a highly specific antibody produce in the rabbit. Dynamic tests were performed with ACTH, dexamethasone and estroprogestative drugs and the role played by the adrenals and the ovaries in 17-OH-P production could be assessed. 17-OH-P determination is of interest in that, it allows the diagnosis of 21-hydroxylase deficiency, where values above 10 ng/ml are often found. Associated with the measure of testosterone and delta 4-androstenedione, it is also useful in the management of the disease. In the mild form of congenital adrenal hyperplasia with late revelation of the symptoms, determination of 17-OH-P following ACTH stimulation allows of relative diagnosis.", "contents": "[Value of 17-hydroxyprogesterone determination in exploration of adrenal cortex enzyme deficiencies]. 17-hydroxyprogesterone (17-OH-P) was measured in various populations by radioimmunoassay, using a highly specific antibody produce in the rabbit. Dynamic tests were performed with ACTH, dexamethasone and estroprogestative drugs and the role played by the adrenals and the ovaries in 17-OH-P production could be assessed. 17-OH-P determination is of interest in that, it allows the diagnosis of 21-hydroxylase deficiency, where values above 10 ng/ml are often found. Associated with the measure of testosterone and delta 4-androstenedione, it is also useful in the management of the disease. In the mild form of congenital adrenal hyperplasia with late revelation of the symptoms, determination of 17-OH-P following ACTH stimulation allows of relative diagnosis."} {"id": "PMID:159771", "title": "Chronic pain syndromes and their treatment. III. The piriformis syndrome.", "content": "The piriformis is a deep-seated muscle, most of its muscular portion being part of the dorsal wall of the pelvis. The lateral portion and its insertion is extra-pelvic and lies deep to the glutei. Like more superficially located and therefore more easily accessible skeletal muscles, the piriformis too can be the seat of trigger points, giving rise to symptoms indistinguishable from those of other causes of low backache, unless a deliberate search is made for the signs specific to the piriformis syndrome. Having made a presumptive diagnosis, confirmation is gained by palpating the muscle itself via rectum or vagina and reproducing the pain by digital pressure. If this test also is positive, the muscle is injected, the approach being either through the sciatic notch, from the perineum, or through the vagina. Immediate relief of pain is experienced after the solution of local anaesthetic and steroid has been deposited deep within the fleshy portion of the muscle.", "contents": "Chronic pain syndromes and their treatment. III. The piriformis syndrome. The piriformis is a deep-seated muscle, most of its muscular portion being part of the dorsal wall of the pelvis. The lateral portion and its insertion is extra-pelvic and lies deep to the glutei. Like more superficially located and therefore more easily accessible skeletal muscles, the piriformis too can be the seat of trigger points, giving rise to symptoms indistinguishable from those of other causes of low backache, unless a deliberate search is made for the signs specific to the piriformis syndrome. Having made a presumptive diagnosis, confirmation is gained by palpating the muscle itself via rectum or vagina and reproducing the pain by digital pressure. If this test also is positive, the muscle is injected, the approach being either through the sciatic notch, from the perineum, or through the vagina. Immediate relief of pain is experienced after the solution of local anaesthetic and steroid has been deposited deep within the fleshy portion of the muscle."} {"id": "PMID:159772", "title": "Effect of a vegetarian diet and dexamethasone on plasma prolactin, testosterone and dehydroepiandrosterone in men and women.", "content": "This study reports the effect of a vegetarian diet and dexamethasone administration on the hormone status of healthy Caucasian men and premenopausal women. A lower nocturnal release of prolactin and testosterone occurred in men fed a vegetarian diet, while in women, dexamethasone administration decreased the nocturnal release of prolactin and caused a greater decrease of plasma dehydroepiandrosterone (DHEA). These results show that diet modification can induce hormonal changes, If similar changes occur in patients with breast and/or prostatic cancer, diet modification may be of benefit in these patients with tumors known to be hormonally dependent.", "contents": "Effect of a vegetarian diet and dexamethasone on plasma prolactin, testosterone and dehydroepiandrosterone in men and women. This study reports the effect of a vegetarian diet and dexamethasone administration on the hormone status of healthy Caucasian men and premenopausal women. A lower nocturnal release of prolactin and testosterone occurred in men fed a vegetarian diet, while in women, dexamethasone administration decreased the nocturnal release of prolactin and caused a greater decrease of plasma dehydroepiandrosterone (DHEA). These results show that diet modification can induce hormonal changes, If similar changes occur in patients with breast and/or prostatic cancer, diet modification may be of benefit in these patients with tumors known to be hormonally dependent."} {"id": "PMID:159773", "title": "Cell proliferation kinetics of epidermis and sebaceous glands in relation to chalone action.", "content": "Median S-phase lengths of pinna epidermis and sebaceous glands, and of epithelia from the oesophagus and under surface of the tongue of Albino Swiss S mice were estimated by the percentage labelled mitoses method (PLM). The 18.4 and 18,8 hr for the median length of S-phase for pinna epidermis and sebaceous glands respectively made it possible for these two tissues to be used experimentally for testing tissue specificity in chalone assay experiments. The 10.0 and 11.5 hr for oesophagus ang tongue epithelium respectively made experimental design for chalone assay difficult when pinna epidermis was the target tissue. The results of the Labelling Index measured each hour throughout a 24-hr period showed no distinct single peaked diurnal rhythm for pinna epidermis and sebaceous glands. Instead a circadian rhythm with several small peaks occurred which would be expected if an S-phase of approximately 18 hr was imposed on the diurnal rhythm. This indicates that there may be very little change in the rate of DNA synthesis. The results are given for the assay in vivo of purified epidermal G1 and G2 chalones, and the 72--81% ethanol precipitate of pig skin from which they could be isolated. These experiments were performed over a time period which took into account the diurnal rhythm of activity of the mice as well as the S-phase lengths. Extrapolating the results with time of action of the chalone shows that the G1 chalone acts at the point of entry into DNA synthesis and that the S-phase length was approximately 17 hr for both the pinna epidermis and sebaceous glands. This may be a more correct value since the PLM method overestimates the median S-phase length as it is known that in pinna skin the [3H]TdR is available to the tissues for 2 hr and true flash labelling does not take place. The previous reports that epidermal G1 chalone acts some hours prior to entry into S-phase resulted from experiments on back skin where the S-phase is shorter and there is a pronounced diurnal rhythm which could mask the chalone effect. The epidermal G2 chalone had no effect on DNA synthesis even at different times in the circadian rhythm. Thus the circadian rhythms and S-phase lengths of the test tissues need to be considered when experiments are performed with chalones. Ideally, the target tissues selected for cell line specificity tests should have the same cell kinetics for the easier and more accurate assessment and interpretation of results. When the tissues have markedly different cell kinetics, experimental procedures and results need to be evaluated accordingly. The point of action of G1 chalone can only be assessed if the effect is measured over the peak of incorporation of [3H]TdR into DNA. The results of the effects of skin extracts are analysed in relation to changes in the availability of [3H]TdR for the incorporation into DNA and to the possibility of there being two distinct populations of proliferating cells.", "contents": "Cell proliferation kinetics of epidermis and sebaceous glands in relation to chalone action. Median S-phase lengths of pinna epidermis and sebaceous glands, and of epithelia from the oesophagus and under surface of the tongue of Albino Swiss S mice were estimated by the percentage labelled mitoses method (PLM). The 18.4 and 18,8 hr for the median length of S-phase for pinna epidermis and sebaceous glands respectively made it possible for these two tissues to be used experimentally for testing tissue specificity in chalone assay experiments. The 10.0 and 11.5 hr for oesophagus ang tongue epithelium respectively made experimental design for chalone assay difficult when pinna epidermis was the target tissue. The results of the Labelling Index measured each hour throughout a 24-hr period showed no distinct single peaked diurnal rhythm for pinna epidermis and sebaceous glands. Instead a circadian rhythm with several small peaks occurred which would be expected if an S-phase of approximately 18 hr was imposed on the diurnal rhythm. This indicates that there may be very little change in the rate of DNA synthesis. The results are given for the assay in vivo of purified epidermal G1 and G2 chalones, and the 72--81% ethanol precipitate of pig skin from which they could be isolated. These experiments were performed over a time period which took into account the diurnal rhythm of activity of the mice as well as the S-phase lengths. Extrapolating the results with time of action of the chalone shows that the G1 chalone acts at the point of entry into DNA synthesis and that the S-phase length was approximately 17 hr for both the pinna epidermis and sebaceous glands. This may be a more correct value since the PLM method overestimates the median S-phase length as it is known that in pinna skin the [3H]TdR is available to the tissues for 2 hr and true flash labelling does not take place. The previous reports that epidermal G1 chalone acts some hours prior to entry into S-phase resulted from experiments on back skin where the S-phase is shorter and there is a pronounced diurnal rhythm which could mask the chalone effect. The epidermal G2 chalone had no effect on DNA synthesis even at different times in the circadian rhythm. Thus the circadian rhythms and S-phase lengths of the test tissues need to be considered when experiments are performed with chalones. Ideally, the target tissues selected for cell line specificity tests should have the same cell kinetics for the easier and more accurate assessment and interpretation of results. When the tissues have markedly different cell kinetics, experimental procedures and results need to be evaluated accordingly. The point of action of G1 chalone can only be assessed if the effect is measured over the peak of incorporation of [3H]TdR into DNA. The results of the effects of skin extracts are analysed in relation to changes in the availability of [3H]TdR for the incorporation into DNA and to the possibility of there being two distinct populations of proliferating cells."} {"id": "PMID:159774", "title": "Ultrastructural and biochemical study of extracellular matrix vesicles in normal alveolar bone of rats.", "content": "The occurrence of vesicles in the extracellular matrix of alveolar bone of normal young rats was demonstrated by both ultrastructural and enzymatic studies. Transmission electron microscopy revealed abundant vesicles in the matrix. The presence of hydroxyapatite crystals, both within the vesicles and in the matrix, was affiliated with rupture of the vesicular membrane. Calcifying nodules were scarce. High levels of both specific and total activities of alkaline- and pyrophosphatases were found in the fraction of isolated vesicles. This fraction also showed activities of different ATPases and acid phosphatase.", "contents": "Ultrastructural and biochemical study of extracellular matrix vesicles in normal alveolar bone of rats. The occurrence of vesicles in the extracellular matrix of alveolar bone of normal young rats was demonstrated by both ultrastructural and enzymatic studies. Transmission electron microscopy revealed abundant vesicles in the matrix. The presence of hydroxyapatite crystals, both within the vesicles and in the matrix, was affiliated with rupture of the vesicular membrane. Calcifying nodules were scarce. High levels of both specific and total activities of alkaline- and pyrophosphatases were found in the fraction of isolated vesicles. This fraction also showed activities of different ATPases and acid phosphatase."} {"id": "PMID:159775", "title": "The abdominal muscle receptor organ in Astacus leptodactylus (Crustacea).", "content": "The structure of both the slow- and the fast-adapting abdominal muscle receptor organ of Astacus leptodactylus is described with particular reference to differences between the two systems. The receptors are composed of a thin muscle that extends from the front edge of one segment to the front edge of the following and a sensory cell connected with this muscle. In the zone where the sensory cells enter their respective muscle, muscle fibers are reduced (zone of relative muscle exclusion = ZRME) and partly replaced by connective tissue. The occurrence of dendritic processes of both the slow and the fast neurons is confined to this zone. The following differences between the two receptor types are established: (1) The fast receptor muscle reveals a smaller sarcomere length than the slow receptor muscle and a higher myosin/actin filament ratio. (2) Muscle fibers that pass the ZRME are always found at its periphery in the fast system, separated from dendritic processes by layers of connective tissue, while in the slow system muscle fibers frequently are intermingled with the sensory elements. (3) The ZRME of the slow receptor is 20-30% longer than that of the fast receptor. (4) The dendritic varicosities of the slow neuron, on an average, contain many more mitochondria than those of the fast neuron. (5) Dendritic processes (fine twigs as well as varicosities) are juxtaposed to the sarcolemma of the muscle fibers only in the slow system; in the fast system dendrites and muscle are spatially separated by connective tissue. It is assumed that these differences between the two receptor types are at least in part responsible for the different thresholds observed in physiological experiments.", "contents": "The abdominal muscle receptor organ in Astacus leptodactylus (Crustacea). The structure of both the slow- and the fast-adapting abdominal muscle receptor organ of Astacus leptodactylus is described with particular reference to differences between the two systems. The receptors are composed of a thin muscle that extends from the front edge of one segment to the front edge of the following and a sensory cell connected with this muscle. In the zone where the sensory cells enter their respective muscle, muscle fibers are reduced (zone of relative muscle exclusion = ZRME) and partly replaced by connective tissue. The occurrence of dendritic processes of both the slow and the fast neurons is confined to this zone. The following differences between the two receptor types are established: (1) The fast receptor muscle reveals a smaller sarcomere length than the slow receptor muscle and a higher myosin/actin filament ratio. (2) Muscle fibers that pass the ZRME are always found at its periphery in the fast system, separated from dendritic processes by layers of connective tissue, while in the slow system muscle fibers frequently are intermingled with the sensory elements. (3) The ZRME of the slow receptor is 20-30% longer than that of the fast receptor. (4) The dendritic varicosities of the slow neuron, on an average, contain many more mitochondria than those of the fast neuron. (5) Dendritic processes (fine twigs as well as varicosities) are juxtaposed to the sarcolemma of the muscle fibers only in the slow system; in the fast system dendrites and muscle are spatially separated by connective tissue. It is assumed that these differences between the two receptor types are at least in part responsible for the different thresholds observed in physiological experiments."} {"id": "PMID:159776", "title": "Capillary distribution and metabolic histochemistry of the lateral propulsive musculature of pelagic teleost fish.", "content": "Metabolic and vascular adaptation of teleost lateral propulsive musculature to an active mode of life was investigated in four pelagic teleosts (mackerel, yellowtail scad, pilchard and Australian salmon). Histochemical profiles and capillarisation data of the red and white muscle were compared to those of less active demersal species. Pelagic white muscle stained positively for the aerobic enzymes succinate dehydrogenase and NADH diaphorase, and had both subsarcolemmal and intermyofibrillar mitochondria which corresponded to the loci of the histochemical stain. Subsarcolemmal mitochondria tended to be localised close to capillaries. In contrast, white muscle from demersal species was unstained for the same enzymes and was devoid of mitochondria. Red muscle of all species had abundant mitochondria and stained intensely for aerobic enzymes. Capillarisation was quantified by determining the percentage of fibres surrounded by a given number of peripheral capillaries, mean fibre diameter, mean number of peripheral capillaries, capillary: fibre ratio and sharing factor where appropriate. Red muscle of mackerel, Australian salmon, pilchard and scad are better vascularised than red muscle of the flathead having 153, 200, 242, 291 and 309 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. White muscle of mackerel, pilchard and scad are better vascularised than white muscle of the Australian salmon and flathead having 2040, 3367, 4992, 9893 and 10,469 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. Red muscle of Australian salmon had distinct regional variation. Deep red muscle was found to be more highly vascularised (4.2 peripheral capillaries per muscle fibre) than lateral red muscle (1.9 peripheral capillaries per muscle fibre). Red muscle of the other species was less heterogeneous. White muscle capillarisation was slightly variable in all species. It is concluded that the white muscle of the pelagic species studied is functionally and structurally adapted for sustained aerobic activity with relatively abundant mitochondria being preferentially situated close to the source of gas and metabolite exchange.", "contents": "Capillary distribution and metabolic histochemistry of the lateral propulsive musculature of pelagic teleost fish. Metabolic and vascular adaptation of teleost lateral propulsive musculature to an active mode of life was investigated in four pelagic teleosts (mackerel, yellowtail scad, pilchard and Australian salmon). Histochemical profiles and capillarisation data of the red and white muscle were compared to those of less active demersal species. Pelagic white muscle stained positively for the aerobic enzymes succinate dehydrogenase and NADH diaphorase, and had both subsarcolemmal and intermyofibrillar mitochondria which corresponded to the loci of the histochemical stain. Subsarcolemmal mitochondria tended to be localised close to capillaries. In contrast, white muscle from demersal species was unstained for the same enzymes and was devoid of mitochondria. Red muscle of all species had abundant mitochondria and stained intensely for aerobic enzymes. Capillarisation was quantified by determining the percentage of fibres surrounded by a given number of peripheral capillaries, mean fibre diameter, mean number of peripheral capillaries, capillary: fibre ratio and sharing factor where appropriate. Red muscle of mackerel, Australian salmon, pilchard and scad are better vascularised than red muscle of the flathead having 153, 200, 242, 291 and 309 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. White muscle of mackerel, pilchard and scad are better vascularised than white muscle of the Australian salmon and flathead having 2040, 3367, 4992, 9893 and 10,469 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. Red muscle of Australian salmon had distinct regional variation. Deep red muscle was found to be more highly vascularised (4.2 peripheral capillaries per muscle fibre) than lateral red muscle (1.9 peripheral capillaries per muscle fibre). Red muscle of the other species was less heterogeneous. White muscle capillarisation was slightly variable in all species. It is concluded that the white muscle of the pelagic species studied is functionally and structurally adapted for sustained aerobic activity with relatively abundant mitochondria being preferentially situated close to the source of gas and metabolite exchange."} {"id": "PMID:159787", "title": "The cytoplasmic origin of variability in the timing of S phase in mammalian cells.", "content": "The time at which S phase begins in mammalian cells is highly variable with respect to cell age. Evidence is presented that this variability does not arise because the initiation of DNA synthesis depends on the stochastic interaction of an initiator substance with a rare initiation site. Instead, the signal responsible for starting S phase must appear at random in the cytoplasm and may be transient.", "contents": "The cytoplasmic origin of variability in the timing of S phase in mammalian cells. The time at which S phase begins in mammalian cells is highly variable with respect to cell age. Evidence is presented that this variability does not arise because the initiation of DNA synthesis depends on the stochastic interaction of an initiator substance with a rare initiation site. Instead, the signal responsible for starting S phase must appear at random in the cytoplasm and may be transient."} {"id": "PMID:159793", "title": "Immune depression in trypanosome-infected mice. IV. Kinetics of suppression and alleviation by the trypanocidal drug Berenil.", "content": "Mice infected with T. congolense were monitored for numbers of parasites in peripheral blood, changes in spleen cell populations, immune depression and suppressor cell activity. Depression of B and T lymphocyte responses and the appearance of suppressor cell activity in spleens of infected mice paralleled the appearance of parasites in the peripheral blood. The immune depression was manifest before any visible changes in spleen cell populations occurred. Treatment of infected mice with the trypanocidal drug Berenil resulted in a rapid clearance of parasites from the peripheral blood, a parallel loss of immune depression and suppressor cell activity and a gradual return towards normal spleen cell composition. The splenic white pulp showed severe depletion following longstanding infection with T. congolense. However, following treatment with Berenil there was rapid repopulation of the white pulp and widespread active germinal centre formation.", "contents": "Immune depression in trypanosome-infected mice. IV. Kinetics of suppression and alleviation by the trypanocidal drug Berenil. Mice infected with T. congolense were monitored for numbers of parasites in peripheral blood, changes in spleen cell populations, immune depression and suppressor cell activity. Depression of B and T lymphocyte responses and the appearance of suppressor cell activity in spleens of infected mice paralleled the appearance of parasites in the peripheral blood. The immune depression was manifest before any visible changes in spleen cell populations occurred. Treatment of infected mice with the trypanocidal drug Berenil resulted in a rapid clearance of parasites from the peripheral blood, a parallel loss of immune depression and suppressor cell activity and a gradual return towards normal spleen cell composition. The splenic white pulp showed severe depletion following longstanding infection with T. congolense. However, following treatment with Berenil there was rapid repopulation of the white pulp and widespread active germinal centre formation."} {"id": "PMID:159795", "title": "The clinical spectrum of Reiter's syndrome and similar postenteric arthropathies.", "content": "Certain infections of the genitourinary and gastrointestinal tracts, such as nongonococcal urethritis, dysentery and yersiniosis, precipitate characteristic arthritic syndromes in genetically susceptible individuals. Eye and skin lesions in the form of conjunctivitis, iritis, keratodermia blenorrhagica and erythema nodosum occurring in association with particular distributions of arthritis make recognizable clinical entities. Reiter's syndrome may be diagnosed with certainty from the presence of tender heels, low back pain, a predominance of knee and foot arthritis and pyuria, when the more obvious clinical markers of the syndrome are absent; a flagrant case represents one of the easiest clinical diagnoses in medicine. Diagnosis is important for a good prognosis, optimal treatment and sometimes prophylactic measures. Sacroiliitis often progressing to spinal ankylosis is a prominant feature in the B27-positive patient. Erythema nodosum occurs in B27-negative subjects as a response to yersiniosis and ulcerative colitis.", "contents": "The clinical spectrum of Reiter's syndrome and similar postenteric arthropathies. Certain infections of the genitourinary and gastrointestinal tracts, such as nongonococcal urethritis, dysentery and yersiniosis, precipitate characteristic arthritic syndromes in genetically susceptible individuals. Eye and skin lesions in the form of conjunctivitis, iritis, keratodermia blenorrhagica and erythema nodosum occurring in association with particular distributions of arthritis make recognizable clinical entities. Reiter's syndrome may be diagnosed with certainty from the presence of tender heels, low back pain, a predominance of knee and foot arthritis and pyuria, when the more obvious clinical markers of the syndrome are absent; a flagrant case represents one of the easiest clinical diagnoses in medicine. Diagnosis is important for a good prognosis, optimal treatment and sometimes prophylactic measures. Sacroiliitis often progressing to spinal ankylosis is a prominant feature in the B27-positive patient. Erythema nodosum occurs in B27-negative subjects as a response to yersiniosis and ulcerative colitis."} {"id": "PMID:159799", "title": "Penetration of protective gloves by epoxy resin.", "content": "A gas jointer developed dermatitis from epoxy resin of Bisphenol A type. This substance penetrates plastic and rubber gloves. The man was compelled to change his job. There is a need for new types of gloves which are impermeable. The wearing of the existing types of glove by those not sensitised may be worthwhile because it probably lessens the dose of allergen absorbed and hence lessens the incidence of sensitisation.", "contents": "Penetration of protective gloves by epoxy resin. A gas jointer developed dermatitis from epoxy resin of Bisphenol A type. This substance penetrates plastic and rubber gloves. The man was compelled to change his job. There is a need for new types of gloves which are impermeable. The wearing of the existing types of glove by those not sensitised may be worthwhile because it probably lessens the dose of allergen absorbed and hence lessens the incidence of sensitisation."} {"id": "PMID:159800", "title": "Captafol dermatitis in the timber industry.", "content": "Captafol is a common cause of dermatitis amongst workers in the timber industry. In a survey of 14 timber treatment plants 23% of 133 workers exposed to captafol gave a history suggestive of occupationally induced dermatitis. Although allergic dermatitis can occur, irritant dermatitis is far more common. Attention to plant and personal hygiene will reduce the prevalence of captafol dermatitis significantly. Recommendations on how to achieve this are made. \"The ultimate end...is not knowledge, but action. To be half right on time may be more important than to obtain the whole truth too late.\"", "contents": "Captafol dermatitis in the timber industry. Captafol is a common cause of dermatitis amongst workers in the timber industry. In a survey of 14 timber treatment plants 23% of 133 workers exposed to captafol gave a history suggestive of occupationally induced dermatitis. Although allergic dermatitis can occur, irritant dermatitis is far more common. Attention to plant and personal hygiene will reduce the prevalence of captafol dermatitis significantly. Recommendations on how to achieve this are made. \"The ultimate end...is not knowledge, but action. To be half right on time may be more important than to obtain the whole truth too late.\""} {"id": "PMID:159801", "title": "Oil of turpentine--a disappearing allergen.", "content": "Oil of turpentine has become an infrequent allergen because of its replacement by the petroleum product white spirit, its deliberate exclusion from industrial products, and because the balsam oils used nowadays do not contain the sensitiser delta 3-carene. On the basis of the generally low incidence of sensitisation being currently recorded, the International Contact Dermatitis Group recommend that oil of turpentine be removed from standard patch test series.", "contents": "Oil of turpentine--a disappearing allergen. Oil of turpentine has become an infrequent allergen because of its replacement by the petroleum product white spirit, its deliberate exclusion from industrial products, and because the balsam oils used nowadays do not contain the sensitiser delta 3-carene. On the basis of the generally low incidence of sensitisation being currently recorded, the International Contact Dermatitis Group recommend that oil of turpentine be removed from standard patch test series."} {"id": "PMID:159808", "title": "Acne vulgaris associated with antigonadotropic (Danazol) therapy.", "content": "A case of a young woman in whom nodulocystic acne developed while being treated for endometriosis with danazol, an antigonadotropic drug, is described herein. Although this agent, a derivative of 17 alpha-ethinyl testosterone, has been noted to possess weak androgenic properties, it has not been widely appreciated that danazol's androgenic side effects, particularly acne and seborrhea, occur frequently and may require prompt treatment.", "contents": "Acne vulgaris associated with antigonadotropic (Danazol) therapy. A case of a young woman in whom nodulocystic acne developed while being treated for endometriosis with danazol, an antigonadotropic drug, is described herein. Although this agent, a derivative of 17 alpha-ethinyl testosterone, has been noted to possess weak androgenic properties, it has not been widely appreciated that danazol's androgenic side effects, particularly acne and seborrhea, occur frequently and may require prompt treatment."} {"id": "PMID:159810", "title": "Hypertrophic obstructive cardiomyopathy and coronary artery spasm.", "content": "Three patients had hypertrophic obstructive cardiomyopathy and coronary artery spasm. The clinical diagnosis of hypertrophic obstructive cardiomyopathy, in all patients, was confirmed by echocardiography and angiography. Significant spasm of the right coronary artery was demonstrated in each patient by selective coronary arteriography. One patient had atherosclerotic obstructive three vessel disease, while the other two showed no evidence of any fixed organic narrowing of the coronary arteries. ST segment elevation in the inferior ECG leads was documented in two of the patients in association with coronary spasm.", "contents": "Hypertrophic obstructive cardiomyopathy and coronary artery spasm. Three patients had hypertrophic obstructive cardiomyopathy and coronary artery spasm. The clinical diagnosis of hypertrophic obstructive cardiomyopathy, in all patients, was confirmed by echocardiography and angiography. Significant spasm of the right coronary artery was demonstrated in each patient by selective coronary arteriography. One patient had atherosclerotic obstructive three vessel disease, while the other two showed no evidence of any fixed organic narrowing of the coronary arteries. ST segment elevation in the inferior ECG leads was documented in two of the patients in association with coronary spasm."} {"id": "PMID:159812", "title": "Formation and properties of reactive aldehydes.", "content": "4-Hydroxyalkenals react easily with SH groups in enzymes and structural proteins to give stable adducts in which the aldehyde is bound through a thioether linkage to the protein. This reaction represents the mechanism by which these compounds block certain metabolic processes (DNA, RNA and protein synthesis, respiration, glycolysis) and exert their antitumour activity. A highly significant inverse correlation exists between the number of hydroxypentenal-sensitive SH groups in the soluble proteins and the doubling time of 12 transplantable animal tumours. Hydroxyalkenals applied peritumourally completely prevent or significantly delay growth of the solid forms of four animal tumours. The almost non-toxic adducts of 4-hydroxypentenal-cysteine 1:1 and crotonal-cysteine 1:2 applied intraperitoneally prevent or inhibit growth of Ehrlich ascites tumour in mice. The possible formation of unsaturated aldehydes in vivo from lipids, carbohydrates and diamines is discussed.", "contents": "Formation and properties of reactive aldehydes. 4-Hydroxyalkenals react easily with SH groups in enzymes and structural proteins to give stable adducts in which the aldehyde is bound through a thioether linkage to the protein. This reaction represents the mechanism by which these compounds block certain metabolic processes (DNA, RNA and protein synthesis, respiration, glycolysis) and exert their antitumour activity. A highly significant inverse correlation exists between the number of hydroxypentenal-sensitive SH groups in the soluble proteins and the doubling time of 12 transplantable animal tumours. Hydroxyalkenals applied peritumourally completely prevent or significantly delay growth of the solid forms of four animal tumours. The almost non-toxic adducts of 4-hydroxypentenal-cysteine 1:1 and crotonal-cysteine 1:2 applied intraperitoneally prevent or inhibit growth of Ehrlich ascites tumour in mice. The possible formation of unsaturated aldehydes in vivo from lipids, carbohydrates and diamines is discussed."} {"id": "PMID:159813", "title": "Carcinostatic activity of methylglyoxal and related substances in tumour-bearing mice.", "content": "Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, in contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. Methylglyoxal and hpe are potent carcinostatic agents in vitro but relatively ineffective in vivo. Both aldehydes have a short half-life in vivo which may explain their poor carcinostatic properties when administered other than peritumorally. Several possibilities of increasing the effective half-life were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration of an inhibitor of glyoxalase I, (iii) administration of aldehyde-cysteine adducts, and (iv continuous intravenous infusion. Methylglyoxal (36 mg/kg i.p., twice daily) was slightly less effective in inhibiting the growth of the solid form of Ehrlich carcinoma than a dose of 72 mg/kg (inj. 1); 36 mg/kg (inj. 2) 46.2% compared to 51%. The aldehyde was more effective aginst the ascitic form of the tumour, with 99.76% inhibition of growth after giving 72 mg/kg twice daily for five days followed by 36 mg/kg for five days. The glyoxalase I inhibitor S-(p-bromobenzyl)-glutathione didnot significantly enhance the activity of methylglyoxal against the solid form of the tumour. Nicotinamide (1% w/v in the drink) was similarily inactive. Methylglyoxal in combination with nicotinamide was significantly more effect (P less than 0.05) than methylglyoxal alone (36 mg/kg, twice daily) in inhibiting the growth of the ascitic tumour. Methylglyoxal-N-acetyl-L-cysteine was four times less toxic than methylglyoxalalone but was marginally less effective against the ascitic form of the tumour. Doses of these adducts equivalent to 144 mg/kg per day of methylglyoxal were more effective P less than 0.05) than the optimal regime of methylglyoxal in inhibiting the solid tumour (67.5% inhibition compared to 51%). Treatment of mice bearing the ascitic form of Sarcoma 180 with five daily doses (i.p.) of an HPE-cysteine adduct equivalent to a dose of HPE alone of 32-256 mg/kg per day significantly increased survival time by comparison with controls. The adduct was 2-3 times more effective, dose-for-dose, than HPE alone in inhibiting tumour growth. Purified buffered methylglyoxal has an LD50 on continuous infusion into the right lateral tail vein in mice of more than 3.0 mg/g per day (seven days at 2.8 ml/day). Local oedema followed by tail necrosis occurs at doses in excess of 0.25-0.5 mg/g per day in mice bearing the solid forms of the syngeneic tumours: squamous carcinoma D; lymphosarcoma 1 (WH/Ht mice); and spontaneous mammary D5056 (CBA/CA mice). A maximum tumour volume growth delay of 3.4 days at Day 17 (P less than 0.001) after transplantation was observed after infusion of 0.5 mg/g per day methylglyoxal on Days 11-17 in the CBA/CA D40 syngeneic mammary tumour. Tumour regrowth after termination of therapy eliminated the significant difference between control and methylglyoxal-treated tumours by Day 27. Methylglyoxal infusion (0...", "contents": "Carcinostatic activity of methylglyoxal and related substances in tumour-bearing mice. Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, in contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. Methylglyoxal and hpe are potent carcinostatic agents in vitro but relatively ineffective in vivo. Both aldehydes have a short half-life in vivo which may explain their poor carcinostatic properties when administered other than peritumorally. Several possibilities of increasing the effective half-life were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration of an inhibitor of glyoxalase I, (iii) administration of aldehyde-cysteine adducts, and (iv continuous intravenous infusion. Methylglyoxal (36 mg/kg i.p., twice daily) was slightly less effective in inhibiting the growth of the solid form of Ehrlich carcinoma than a dose of 72 mg/kg (inj. 1); 36 mg/kg (inj. 2) 46.2% compared to 51%. The aldehyde was more effective aginst the ascitic form of the tumour, with 99.76% inhibition of growth after giving 72 mg/kg twice daily for five days followed by 36 mg/kg for five days. The glyoxalase I inhibitor S-(p-bromobenzyl)-glutathione didnot significantly enhance the activity of methylglyoxal against the solid form of the tumour. Nicotinamide (1% w/v in the drink) was similarily inactive. Methylglyoxal in combination with nicotinamide was significantly more effect (P less than 0.05) than methylglyoxal alone (36 mg/kg, twice daily) in inhibiting the growth of the ascitic tumour. Methylglyoxal-N-acetyl-L-cysteine was four times less toxic than methylglyoxalalone but was marginally less effective against the ascitic form of the tumour. Doses of these adducts equivalent to 144 mg/kg per day of methylglyoxal were more effective P less than 0.05) than the optimal regime of methylglyoxal in inhibiting the solid tumour (67.5% inhibition compared to 51%). Treatment of mice bearing the ascitic form of Sarcoma 180 with five daily doses (i.p.) of an HPE-cysteine adduct equivalent to a dose of HPE alone of 32-256 mg/kg per day significantly increased survival time by comparison with controls. The adduct was 2-3 times more effective, dose-for-dose, than HPE alone in inhibiting tumour growth. Purified buffered methylglyoxal has an LD50 on continuous infusion into the right lateral tail vein in mice of more than 3.0 mg/g per day (seven days at 2.8 ml/day). Local oedema followed by tail necrosis occurs at doses in excess of 0.25-0.5 mg/g per day in mice bearing the solid forms of the syngeneic tumours: squamous carcinoma D; lymphosarcoma 1 (WH/Ht mice); and spontaneous mammary D5056 (CBA/CA mice). A maximum tumour volume growth delay of 3.4 days at Day 17 (P less than 0.001) after transplantation was observed after infusion of 0.5 mg/g per day methylglyoxal on Days 11-17 in the CBA/CA D40 syngeneic mammary tumour. Tumour regrowth after termination of therapy eliminated the significant difference between control and methylglyoxal-treated tumours by Day 27. Methylglyoxal infusion (0..."} {"id": "PMID:159815", "title": "Regulation of mitotic activity in rat vaginal epithelium: relationships between the level of its inhibitor (G2-chalone) and estrogens.", "content": "The level of a tissue-specific inhibitor of mitotic activity (G2-chalone) and mitotic activity in the vaginal mucosa of cycling rats of varying age and castrated rats were studied. A direct correlation between the level of the inhibitor and mitotic index is found in cycling animals. Both parameters are maximal during estrus and minimal in proestrus, when estrogen level in blood circulation is the highest. The undulating variations in G2 inhibitor level during estrous cycle are less pronounced and the concentrations of the inhibitor in relevant phases are significantly lower in aged females than in adult rats. Administration of estradiol benzoate (1 microgram/100 g) to castrated female rats was followed by a significant decrease in mitotic inhibitor level in vaginal mucosa within 12 hrs. This, in turn, was followed by a rise in mitotic activity 18 hr after estrogen administration. Therefore, the estrogen exerts its effect on mitotic activity in target tissue after it has induced a decrease in the level of the antimitotic factor (G2-chalone).", "contents": "Regulation of mitotic activity in rat vaginal epithelium: relationships between the level of its inhibitor (G2-chalone) and estrogens. The level of a tissue-specific inhibitor of mitotic activity (G2-chalone) and mitotic activity in the vaginal mucosa of cycling rats of varying age and castrated rats were studied. A direct correlation between the level of the inhibitor and mitotic index is found in cycling animals. Both parameters are maximal during estrus and minimal in proestrus, when estrogen level in blood circulation is the highest. The undulating variations in G2 inhibitor level during estrous cycle are less pronounced and the concentrations of the inhibitor in relevant phases are significantly lower in aged females than in adult rats. Administration of estradiol benzoate (1 microgram/100 g) to castrated female rats was followed by a significant decrease in mitotic inhibitor level in vaginal mucosa within 12 hrs. This, in turn, was followed by a rise in mitotic activity 18 hr after estrogen administration. Therefore, the estrogen exerts its effect on mitotic activity in target tissue after it has induced a decrease in the level of the antimitotic factor (G2-chalone)."} {"id": "PMID:159818", "title": "Active transport of calcium in membrane vesicles from Mycobacterium phlei.", "content": "Active transport of calcium ions has been demonstrated in inside-out membrane vesicles from Mycobacterium phlei mediated by respiratory linked substrates as well as by ATP hydrolysis. The uptake of calcium exhibited an apparent Km of 80 microM and V of 16.6 nmol calcium uptake x min-1 x mg protein-1. A fortyfold concentration gradient for calcium ions was calculated for both the ATP-induced and the respiration-induced transport of calcium. Removal of coupling-factor-latent ATPase resulted in the complete loss of ATP-driven Ca2+ transport whereas the respiration-driven uptake was reduced by 40-50%. The uptake of calcium was inhibited by the proton conducting ionophores carbonylcyanide m-chlorophenylhydrazone and Gramicidin-D. The accumulated calcium was freely exchangeable with external calcium and was rapidly released by the addition of inhibitors of energy transduction, proton-translocating uncouplers or the ionophore A23187. The uptake of the weak base, methylamine, upon the oxidation of respiratory-linked substrates or the hydrolysis of ATP showed the generation of a protein gradient (inside acidic) which was partially collapsed on the addition of calcium ions. These results suggest that a Ca2+/H+ antiport mechanism may be responsible for the transport of calcium.", "contents": "Active transport of calcium in membrane vesicles from Mycobacterium phlei. Active transport of calcium ions has been demonstrated in inside-out membrane vesicles from Mycobacterium phlei mediated by respiratory linked substrates as well as by ATP hydrolysis. The uptake of calcium exhibited an apparent Km of 80 microM and V of 16.6 nmol calcium uptake x min-1 x mg protein-1. A fortyfold concentration gradient for calcium ions was calculated for both the ATP-induced and the respiration-induced transport of calcium. Removal of coupling-factor-latent ATPase resulted in the complete loss of ATP-driven Ca2+ transport whereas the respiration-driven uptake was reduced by 40-50%. The uptake of calcium was inhibited by the proton conducting ionophores carbonylcyanide m-chlorophenylhydrazone and Gramicidin-D. The accumulated calcium was freely exchangeable with external calcium and was rapidly released by the addition of inhibitors of energy transduction, proton-translocating uncouplers or the ionophore A23187. The uptake of the weak base, methylamine, upon the oxidation of respiratory-linked substrates or the hydrolysis of ATP showed the generation of a protein gradient (inside acidic) which was partially collapsed on the addition of calcium ions. These results suggest that a Ca2+/H+ antiport mechanism may be responsible for the transport of calcium."} {"id": "PMID:159821", "title": "Urinary acid mucopolysaccharides in multiple sulfatase deficiency (mucosulfatidosis).", "content": "Urinary acid mucopolysaccharides (AMPS) excretion was investigated in a Japanese case with Multiple Sulfatase Deficiency (MSD) (Mucosulfatidosis). The patient excreted AMPS 4 to 5 times more (as carbazoluronic acid) than controls. The cellulose acetate gel electrophoresis clearly indicated two major AMPS which co-migrated with heparan sulfate and chondroitin sulfate A/C. Enzymic digestion with chondroitinase AC and ABC, and by testicular hyaluronidase plus amino sugar analysis also confirmed that our case excreted heparan sulfate and chondroitin sulfate A/C. These findings suggest that there are heterogeneities of urinary AMPS excretion among cases with MSD.", "contents": "Urinary acid mucopolysaccharides in multiple sulfatase deficiency (mucosulfatidosis). Urinary acid mucopolysaccharides (AMPS) excretion was investigated in a Japanese case with Multiple Sulfatase Deficiency (MSD) (Mucosulfatidosis). The patient excreted AMPS 4 to 5 times more (as carbazoluronic acid) than controls. The cellulose acetate gel electrophoresis clearly indicated two major AMPS which co-migrated with heparan sulfate and chondroitin sulfate A/C. Enzymic digestion with chondroitinase AC and ABC, and by testicular hyaluronidase plus amino sugar analysis also confirmed that our case excreted heparan sulfate and chondroitin sulfate A/C. These findings suggest that there are heterogeneities of urinary AMPS excretion among cases with MSD."} {"id": "PMID:159822", "title": "Changes in antiplasmin and plasmin activities during extreme hemodilution and open heart surgery in dogs.", "content": "The effects of extreme hemodilution and open heart surgery on antiplasmin and plasmin activities were investigated in dogs. Assays for plasmin and antiplasmin activities were performed with a chromogenic peptide substrate for plasmin. After hemodilution and during cardiopulmonary bypass (CPB), plasmin activity on the substrate was observed and levels of both \"fast-reacting\" and \"total\" antiplasmins fell. The plasmin activity was shown to be due to the formation of alpha2-macroglobulin-plasmin complex which exhibited amidolytic activity on the chromogenic substrate. The falls in antiplasmin activity together with the appearance of the alpha2-macroglobulin-plasmin complex revealed that activation of the fibrinolytic system had occurred. After the operation and following reinfusion of autologous blood, decreased plasmin and increased antiplasmin activities were observed. On the first and sixth days following the operation plasmin activities were still slightly higher than pre-operation values, whilst antiplasmin activities were normal.", "contents": "Changes in antiplasmin and plasmin activities during extreme hemodilution and open heart surgery in dogs. The effects of extreme hemodilution and open heart surgery on antiplasmin and plasmin activities were investigated in dogs. Assays for plasmin and antiplasmin activities were performed with a chromogenic peptide substrate for plasmin. After hemodilution and during cardiopulmonary bypass (CPB), plasmin activity on the substrate was observed and levels of both \"fast-reacting\" and \"total\" antiplasmins fell. The plasmin activity was shown to be due to the formation of alpha2-macroglobulin-plasmin complex which exhibited amidolytic activity on the chromogenic substrate. The falls in antiplasmin activity together with the appearance of the alpha2-macroglobulin-plasmin complex revealed that activation of the fibrinolytic system had occurred. After the operation and following reinfusion of autologous blood, decreased plasmin and increased antiplasmin activities were observed. On the first and sixth days following the operation plasmin activities were still slightly higher than pre-operation values, whilst antiplasmin activities were normal."} {"id": "PMID:159827", "title": "The in vitro cellular response of human lymphocytes to trinitrophenylated autologous cells: HLA-D restriction of proliferation but apparent absence of HLA restriction of cytolysis.", "content": "Primary as well as secondary proliferative and cytotoxic responses to 2,4,6-trinitrophenyl (TNP)-modified autologous human cells have been studied. Proliferative responses have been obtained both by primary (peak on day 6) and secondary (peak on day 2--3) stimulation. Both responders and nonresponders were found among the panel of unrelated individuals tested. All responders in a secondary reaction also gave significant primary responses. Intrafamilial studies showed that the ability to restimulate a proliferative response followed the major histocompatibility complex haplotype of the responder; in some cases, the two haplotypes differed in their ability to restimulate. Using unrelated individuals typed for HLA-A, B and C, as well as HLA-D and DR, proliferation was shown to occur only when the unrelated stimulator shared HLA-D region products with the responder. In contrast, no HLA restriction was found in cell-mediated lympholysis (CML) (neither in primary nor in secondary responses) in most cases. The data suggest that the observed killing is independent of sensitization. Both responders and nonresponders in proliferation yielded high levels of lysis; no increase of lysis was found in kinetic studies; most allogeneic CML combinations were highly lytic for the TNP-modified responder cells at a time when the lysis of the specific allogeneic target is negligible. These preliminary data suggest that the killing observed might be different from classical T cell-mediated lympholysis.", "contents": "The in vitro cellular response of human lymphocytes to trinitrophenylated autologous cells: HLA-D restriction of proliferation but apparent absence of HLA restriction of cytolysis. Primary as well as secondary proliferative and cytotoxic responses to 2,4,6-trinitrophenyl (TNP)-modified autologous human cells have been studied. Proliferative responses have been obtained both by primary (peak on day 6) and secondary (peak on day 2--3) stimulation. Both responders and nonresponders were found among the panel of unrelated individuals tested. All responders in a secondary reaction also gave significant primary responses. Intrafamilial studies showed that the ability to restimulate a proliferative response followed the major histocompatibility complex haplotype of the responder; in some cases, the two haplotypes differed in their ability to restimulate. Using unrelated individuals typed for HLA-A, B and C, as well as HLA-D and DR, proliferation was shown to occur only when the unrelated stimulator shared HLA-D region products with the responder. In contrast, no HLA restriction was found in cell-mediated lympholysis (CML) (neither in primary nor in secondary responses) in most cases. The data suggest that the observed killing is independent of sensitization. Both responders and nonresponders in proliferation yielded high levels of lysis; no increase of lysis was found in kinetic studies; most allogeneic CML combinations were highly lytic for the TNP-modified responder cells at a time when the lysis of the specific allogeneic target is negligible. These preliminary data suggest that the killing observed might be different from classical T cell-mediated lympholysis."} {"id": "PMID:159832", "title": "PPD-induced blastogenesis is auto-regulated by suppressor cells generated in vitro.", "content": "Suppressor cell induction can be demonstrated during antigen specific blastogenesis by using the same methods which have shown induction of suppressor cells by Con A. Since suppressor cells are rapidly generated during antigen specific blastogenesis, they must regulate the final level of blastogenesis induced during the seven day in vitro incubation.", "contents": "PPD-induced blastogenesis is auto-regulated by suppressor cells generated in vitro. Suppressor cell induction can be demonstrated during antigen specific blastogenesis by using the same methods which have shown induction of suppressor cells by Con A. Since suppressor cells are rapidly generated during antigen specific blastogenesis, they must regulate the final level of blastogenesis induced during the seven day in vitro incubation."} {"id": "PMID:159836", "title": "A rationale for the therapeutic action of aprotinin.", "content": "Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested.", "contents": "A rationale for the therapeutic action of aprotinin. Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested."} {"id": "PMID:159840", "title": "Effects of levamisole in S\u00e9zary syndrome. Apparent acceleration of disease.", "content": "2 patients with S\u00e9zary syndrome were treated with levamisole. Both patients had clinical and hematological evidence of acceleration of their disease and ultimately died, although 1 patient had improvement in skin test reactivity. We suggest that levamisole be used with caution, if at all, in patients with T-lymphocyte malignancies.", "contents": "Effects of levamisole in S\u00e9zary syndrome. Apparent acceleration of disease. 2 patients with S\u00e9zary syndrome were treated with levamisole. Both patients had clinical and hematological evidence of acceleration of their disease and ultimately died, although 1 patient had improvement in skin test reactivity. We suggest that levamisole be used with caution, if at all, in patients with T-lymphocyte malignancies."} {"id": "PMID:159841", "title": "The retinoic acid derivative Ro 11-1430 (Tasmaderm) in patients with acne vulgaris not tolerating retinoic acid. A controlled multicenter trial against placebo.", "content": "In a double-blind randomized comparative multicenter trial, consisting of 29 patients with acne vulgaris who were unable to tolerate daily applications of retinoic acid, the retinoic acid derivative Ro 11--1430 (0.1% vanishing cream) was compared in a 6--8 weeks topical treatment with vanishing cream alone (placebo). Regarding efficacy, for most criteria measured the response was always better with Ro 11--1430 than with placebo, although the differences were not always statistically significant for several reasons, one probably being the small number of patients in the trial. Regarding tolerance, both treatments were satisfactory. Ro 11---1430 and placebo did not differ significantly regarding frequency and severity of erythema, desquamation and burning. These results suggest that treatment with Ro 11--1430 should be considered in acne patients who are unable to use retinoic acid due to severe local reactions.", "contents": "The retinoic acid derivative Ro 11-1430 (Tasmaderm) in patients with acne vulgaris not tolerating retinoic acid. A controlled multicenter trial against placebo. In a double-blind randomized comparative multicenter trial, consisting of 29 patients with acne vulgaris who were unable to tolerate daily applications of retinoic acid, the retinoic acid derivative Ro 11--1430 (0.1% vanishing cream) was compared in a 6--8 weeks topical treatment with vanishing cream alone (placebo). Regarding efficacy, for most criteria measured the response was always better with Ro 11--1430 than with placebo, although the differences were not always statistically significant for several reasons, one probably being the small number of patients in the trial. Regarding tolerance, both treatments were satisfactory. Ro 11---1430 and placebo did not differ significantly regarding frequency and severity of erythema, desquamation and burning. These results suggest that treatment with Ro 11--1430 should be considered in acne patients who are unable to use retinoic acid due to severe local reactions."} {"id": "PMID:159847", "title": "Gamma-aminobutyric acid in peripheral tissue, with emphasis on the endocrine pancreas: presence in two species and reduction by streptozotocin.", "content": "A screen of selected periphral organs of the rat found that gamma-aminobutyric acid (GABA) is generally present outside the central nervous system, and, of those organs examined, GABA was present at the highest concentration in the pancreas (approximately 40 pmol/mg wet wt). Furthermore, this putative inhibitory neurotransmitter was found to be present at even higher levels in islets of Langerhans tissue isolated from rat pancreas (190 pmol/mg). Administration of streptozotocin, a selective beta-cell toxin, decreased pancreatic GABA levels significantly, but had no or only small effects on the GABA content of other organs. Normal teleost (catfish) Brockmann body contains about the same level of GABA as normal rat islet tissue.", "contents": "Gamma-aminobutyric acid in peripheral tissue, with emphasis on the endocrine pancreas: presence in two species and reduction by streptozotocin. A screen of selected periphral organs of the rat found that gamma-aminobutyric acid (GABA) is generally present outside the central nervous system, and, of those organs examined, GABA was present at the highest concentration in the pancreas (approximately 40 pmol/mg wet wt). Furthermore, this putative inhibitory neurotransmitter was found to be present at even higher levels in islets of Langerhans tissue isolated from rat pancreas (190 pmol/mg). Administration of streptozotocin, a selective beta-cell toxin, decreased pancreatic GABA levels significantly, but had no or only small effects on the GABA content of other organs. Normal teleost (catfish) Brockmann body contains about the same level of GABA as normal rat islet tissue."} {"id": "PMID:159848", "title": "A longitudinal study of very low-birthweight infants. II: Results of controlled trial of intensive care and incidence of handicaps.", "content": "Between 1966 and 1970, infants with birthweights between 1000 and 1500g entered a randomized controlled trial to determine the short-term and long-term results of neonatal intensive care. Of 158 long-term survivors, five were lost to follow-up, but the multidisciplinary research team prospectively followed 143 children up to the age of eight years. Useful data were available for the other 10 children. Of the long-term survivors 74 had received routine, and 84 had received intensive nursery care. At eight years of age there were no statistically significant differences in the frequencies of a variety of individual abnormalities; fewer of the intensively managed children had cerebral palsy, but sensorineural deafness and ocular abnormalities occurred more frequently. Individual children were graded into four carefully defined groups: (a) profound handicap (4.4 per cent of entire study group); (b) severe handicap (10.1 per cent); (c) significant handicap (37.3 per cent); and (d) trivial or no handicap (41.8 per cent). Inadequate data were available for 6.3 per cent of the children. It was apparent that the improved survival attributed to intensive neonatal care was achieved at the expense of additional severely handicapped children, and this feature is discussed.", "contents": "A longitudinal study of very low-birthweight infants. II: Results of controlled trial of intensive care and incidence of handicaps. Between 1966 and 1970, infants with birthweights between 1000 and 1500g entered a randomized controlled trial to determine the short-term and long-term results of neonatal intensive care. Of 158 long-term survivors, five were lost to follow-up, but the multidisciplinary research team prospectively followed 143 children up to the age of eight years. Useful data were available for the other 10 children. Of the long-term survivors 74 had received routine, and 84 had received intensive nursery care. At eight years of age there were no statistically significant differences in the frequencies of a variety of individual abnormalities; fewer of the intensively managed children had cerebral palsy, but sensorineural deafness and ocular abnormalities occurred more frequently. Individual children were graded into four carefully defined groups: (a) profound handicap (4.4 per cent of entire study group); (b) severe handicap (10.1 per cent); (c) significant handicap (37.3 per cent); and (d) trivial or no handicap (41.8 per cent). Inadequate data were available for 6.3 per cent of the children. It was apparent that the improved survival attributed to intensive neonatal care was achieved at the expense of additional severely handicapped children, and this feature is discussed."} {"id": "PMID:159849", "title": "Effect of neocarzinostatin on microtubules.", "content": "Effect of Neocarzinostatin (NCS) on microtubules was examined both in vitro and in vivo. Although NCS had no effect on microtubule assembly in vitro nor dissociated cytoplasmic microtubular network in vivo, microtubular network appeared to be changed to coarse form in NCS-treated 3T3 and HeLa cells. Effect of NCS on microtubules was discussed in comparison with colchicine.", "contents": "Effect of neocarzinostatin on microtubules. Effect of Neocarzinostatin (NCS) on microtubules was examined both in vitro and in vivo. Although NCS had no effect on microtubule assembly in vitro nor dissociated cytoplasmic microtubular network in vivo, microtubular network appeared to be changed to coarse form in NCS-treated 3T3 and HeLa cells. Effect of NCS on microtubules was discussed in comparison with colchicine."} {"id": "PMID:159850", "title": "[Proline-dependent wild strains and proline-dependent mutants of the plague microbe].", "content": "It is found that the growth of Yersinia pestis wild strains, isolated from Citellus musicus Menetri\u00e9 in the Central Caucasus, depends on the presence of proline in the medium. Proline can not be substituted by glutamic acid, other amino acids or vitamins. 28 proline-requiring mutants were selected from Y. pestis marmot strain 20b. Three groups of proline-requiring Y. pestis mutants are established, similar to those of Escherichia coli. The requirement of proline does not affect the virulency, pigment formation and calcium dependence.", "contents": "[Proline-dependent wild strains and proline-dependent mutants of the plague microbe]. It is found that the growth of Yersinia pestis wild strains, isolated from Citellus musicus Menetri\u00e9 in the Central Caucasus, depends on the presence of proline in the medium. Proline can not be substituted by glutamic acid, other amino acids or vitamins. 28 proline-requiring mutants were selected from Y. pestis marmot strain 20b. Three groups of proline-requiring Y. pestis mutants are established, similar to those of Escherichia coli. The requirement of proline does not affect the virulency, pigment formation and calcium dependence."} {"id": "PMID:159851", "title": "Construction and properties of hybrid plasmids carrying the E. coli gal operon.", "content": "A family of hybrid plasmids carrying the entire gal operon of E. coli and designated pgal was constructed in vitro. In the case of pgal 1 (mol. wt. 16.4 Md), a fragment cut by Bam HI endonuclease from lambda gal phage DNA (lambda D-J-gal-att-int) was joined to pMB9 and cloned in the gal-strain of E. coli, which was grown on selective media with galactose as a sole source of carbon. Plasmid pgal2 was derived from pgal 1 by elimination of the 1.1 Md fragment located between the two EcoRI sites and carrying the lambda att-int region and part of pMB9. To obtain pgal3, the 10.7 Md fragment of lambda DNA located between the two SmaI sites (lambda D-J and part of pMB9) in pgal2 was cut out and the resulting flush-end fragments were sealed by the T4DNA ligase. The mol. wt. of pgal3 containing one SmaI site amounted to 4.6 Md, while several pgal3 variants that had lost their SmaI site were still smaller. Plasmid pgal1 inhibited the growth of the gal- host cells, which effect could be overcome by the accompanying helper pMB9. The presence of pgal2 and pgal3 supported the growth and multiplication of gal- cells on selective media even without the helper plasmid. The total amount of pgal plasmid DNA per cell was constant and equalled 60--70 Md (4 copies of pgal1 or 15--16 copies of pgal3, ColE1 or pMB9). This might explain why the co-presence of pMB9 helper does alleviate the \"harmful\" effects of the plasmid pgal1 (which carries att-int genes), by reducing the copy number of the latter from four to one.", "contents": "Construction and properties of hybrid plasmids carrying the E. coli gal operon. A family of hybrid plasmids carrying the entire gal operon of E. coli and designated pgal was constructed in vitro. In the case of pgal 1 (mol. wt. 16.4 Md), a fragment cut by Bam HI endonuclease from lambda gal phage DNA (lambda D-J-gal-att-int) was joined to pMB9 and cloned in the gal-strain of E. coli, which was grown on selective media with galactose as a sole source of carbon. Plasmid pgal2 was derived from pgal 1 by elimination of the 1.1 Md fragment located between the two EcoRI sites and carrying the lambda att-int region and part of pMB9. To obtain pgal3, the 10.7 Md fragment of lambda DNA located between the two SmaI sites (lambda D-J and part of pMB9) in pgal2 was cut out and the resulting flush-end fragments were sealed by the T4DNA ligase. The mol. wt. of pgal3 containing one SmaI site amounted to 4.6 Md, while several pgal3 variants that had lost their SmaI site were still smaller. Plasmid pgal1 inhibited the growth of the gal- host cells, which effect could be overcome by the accompanying helper pMB9. The presence of pgal2 and pgal3 supported the growth and multiplication of gal- cells on selective media even without the helper plasmid. The total amount of pgal plasmid DNA per cell was constant and equalled 60--70 Md (4 copies of pgal1 or 15--16 copies of pgal3, ColE1 or pMB9). This might explain why the co-presence of pMB9 helper does alleviate the \"harmful\" effects of the plasmid pgal1 (which carries att-int genes), by reducing the copy number of the latter from four to one."} {"id": "PMID:159852", "title": "Characterization of mouse ribosomal gene fragments purified by molecular cloning.", "content": "Four mouse ribosomal gene fragments cloned in lambda gtWES were studied by restriction enzyme mapping and Southern transfer experiments. These fragments were found to contain 18S DNA and transcribed as well as non-transcribed spacer DNA. Variation in the structure of these mouse DNA inserts was limited to one region of spacer DNA. This variation may reflect real structural differences found in mouse ribosomal genes or possibly deletion events which occurred during cloning. The transcribed regions of the inserts appear identical to one antoher and restriction enzyme fragments from this region correspond to fragments observed in digests of total mouse DNA. These clones will be useful in studying the structure of transcribed spacer DNA including the ribosomal gene promoter.", "contents": "Characterization of mouse ribosomal gene fragments purified by molecular cloning. Four mouse ribosomal gene fragments cloned in lambda gtWES were studied by restriction enzyme mapping and Southern transfer experiments. These fragments were found to contain 18S DNA and transcribed as well as non-transcribed spacer DNA. Variation in the structure of these mouse DNA inserts was limited to one region of spacer DNA. This variation may reflect real structural differences found in mouse ribosomal genes or possibly deletion events which occurred during cloning. The transcribed regions of the inserts appear identical to one antoher and restriction enzyme fragments from this region correspond to fragments observed in digests of total mouse DNA. These clones will be useful in studying the structure of transcribed spacer DNA including the ribosomal gene promoter."} {"id": "PMID:159853", "title": "A study of the relationship between ex vivo and in vivo effects of sulphinpyrazone in the guinea pig.", "content": "In guinea pigs, sodium arachidonate-induced platelet aggregation ex vivo proved a more sensitive method for detecting drug-related effects after the administration of sulphinpyrazone than collagen-induced platelet aggregation. It was possible to detect inhibition of platelet aggregation after giving sulphinpyrazone orally in a single dose of 3 mg/kg. Excellent correlation was achieved between ex vivo and in vivo inhabition of platelet function with sulphinpyrozone using the Arthus reaction. The results are consistent with the formation, in the guinea pig of metabolites more potent than the parent molecule.", "contents": "A study of the relationship between ex vivo and in vivo effects of sulphinpyrazone in the guinea pig. In guinea pigs, sodium arachidonate-induced platelet aggregation ex vivo proved a more sensitive method for detecting drug-related effects after the administration of sulphinpyrazone than collagen-induced platelet aggregation. It was possible to detect inhibition of platelet aggregation after giving sulphinpyrazone orally in a single dose of 3 mg/kg. Excellent correlation was achieved between ex vivo and in vivo inhabition of platelet function with sulphinpyrozone using the Arthus reaction. The results are consistent with the formation, in the guinea pig of metabolites more potent than the parent molecule."} {"id": "PMID:159855", "title": "[The prognosis for high-risk newborns].", "content": "By good perinatal care the perinatal mortality rate can be brought down to 10 promille. A great number of high risk newborns will survive. The developmental prognosis of these at risk babies has strikingly improved. Among these babies the rate of neuromotor defects has been reduced by about 50%. Babies with birth weights of less than 1501 g will develop spastic diplegia in less than 5% and more than 80% of the babies with birth weights of less than 1001 g and the babies after artificial ventilation will develop normally.", "contents": "[The prognosis for high-risk newborns]. By good perinatal care the perinatal mortality rate can be brought down to 10 promille. A great number of high risk newborns will survive. The developmental prognosis of these at risk babies has strikingly improved. Among these babies the rate of neuromotor defects has been reduced by about 50%. Babies with birth weights of less than 1501 g will develop spastic diplegia in less than 5% and more than 80% of the babies with birth weights of less than 1001 g and the babies after artificial ventilation will develop normally."} {"id": "PMID:159857", "title": "[The concept of social pediatric assistance in the development of handicapped children. Possibilities, problems and future measures].", "content": "Principles and possibilities of the social pediatric concept (Hellbr\u00fcgge) in treatment and aids for handicapped children are demonstrated. Beside positive experiences there are still some unsolved problems: control of therapeutic efficiency, increasing amount of psychic and social handicaps, lack of psychotherapeutic possibilities, problems of the organization and the public r\u00f4le of social pediatric work.", "contents": "[The concept of social pediatric assistance in the development of handicapped children. Possibilities, problems and future measures]. Principles and possibilities of the social pediatric concept (Hellbr\u00fcgge) in treatment and aids for handicapped children are demonstrated. Beside positive experiences there are still some unsolved problems: control of therapeutic efficiency, increasing amount of psychic and social handicaps, lack of psychotherapeutic possibilities, problems of the organization and the public r\u00f4le of social pediatric work."} {"id": "PMID:159858", "title": "Down's syndrome in brother and sister without evident trisomy 21.", "content": "In the present report two siblings with the typical Down's phenotype but without evident full or partial 21 trisomy are described. The finding of a regular 21 trisomy in a minority of the cells in the elder patient favors the hypothesis that both present a hardly demonstrable normal/trisomy 21 mosaicism and may be examples of a constitutional familial tendency to nondisjunction in man.", "contents": "Down's syndrome in brother and sister without evident trisomy 21. In the present report two siblings with the typical Down's phenotype but without evident full or partial 21 trisomy are described. The finding of a regular 21 trisomy in a minority of the cells in the elder patient favors the hypothesis that both present a hardly demonstrable normal/trisomy 21 mosaicism and may be examples of a constitutional familial tendency to nondisjunction in man."} {"id": "PMID:159860", "title": "Pseudocholinesterase activity and E1 phenotypes in Down's syndrome and mental retardation.", "content": "Pseudocholinesterase activity and the phenotypes controlled by the E1 locus have been determined in a sample of 307 Down's syndrome patients and 206 patients suffering from nonspecific mental retardation and compared to those in the healthy population. Both groups of patients have an elevated frequency of phenotypes possessing the rate E1f allele. The mentally retarded patients have a higher mean pseudocholinesterase activity than those with Down's syndrome who, in turn, have activity than the healthy controls.", "contents": "Pseudocholinesterase activity and E1 phenotypes in Down's syndrome and mental retardation. Pseudocholinesterase activity and the phenotypes controlled by the E1 locus have been determined in a sample of 307 Down's syndrome patients and 206 patients suffering from nonspecific mental retardation and compared to those in the healthy population. Both groups of patients have an elevated frequency of phenotypes possessing the rate E1f allele. The mentally retarded patients have a higher mean pseudocholinesterase activity than those with Down's syndrome who, in turn, have activity than the healthy controls."} {"id": "PMID:159861", "title": "The cellular control of delayed hypersensitivity to Staphylococcus aureus in mice.", "content": "The cells which suppressed delayed hypersensitivity (DH) to Staphylococcus aureus in the mice were non-phagocytic, adhered to nylon wool and possessed surface immunoglobulin but no detectable Thy 1. antigen. They were probably B lymphocytes and the suppression which they mediated appeared to be specific. The mature suppressor cells were radiosensitive. Their precursors were sensitive to large doses of cyclophosphamide. Suppressor-cell activity in the spleen reached a peak after two subcutaneous S. aureus infections and declined thereafter. This decline might be related to the appearance of DH to S. aureus in mice after four or more staphylococcal infections.", "contents": "The cellular control of delayed hypersensitivity to Staphylococcus aureus in mice. The cells which suppressed delayed hypersensitivity (DH) to Staphylococcus aureus in the mice were non-phagocytic, adhered to nylon wool and possessed surface immunoglobulin but no detectable Thy 1. antigen. They were probably B lymphocytes and the suppression which they mediated appeared to be specific. The mature suppressor cells were radiosensitive. Their precursors were sensitive to large doses of cyclophosphamide. Suppressor-cell activity in the spleen reached a peak after two subcutaneous S. aureus infections and declined thereafter. This decline might be related to the appearance of DH to S. aureus in mice after four or more staphylococcal infections."} {"id": "PMID:159862", "title": "Human myeloma cells and their strong stimulating capacity in 'one-way' mixed lymphocyte reaction: a comparative study with leukaemic B lymphoid cells.", "content": "Cultured human myeloma cells (ARH-77, RPMI-8226 and U-266), like leukaemic B lymphoid cells, consistently exerted a strong stimulating capacity on allogeneic lymphocytes in the 'one-way' mixed lymphocyte reaction. An optimal stimulation was seen when a 1:1 ratio or 1:2 ratio of responding cell:stimulating cells of each cell line was utilized. The stimulating capacity of ARH-77 or RPMI-8226 cells was significantly diminished when a 1:4 ratio of responding cells:stimulating cells was utilized. Fresh bone marrow cells containing more than 80% plasma cells from a patient with multiple myeloma, on the other hand, failed to exert the stimulating capacity on two occasions. The striking difference between cultured myeloma cells and fresh plasma cells is that the Ia-like antigen is present on cultured myeloma cells, and this antigen is absent on fresh plasma cells. The relationship between the Ia-like antigen and the stimulating capacity in 'one-way' mixed lymphocyte reaction is discussed.", "contents": "Human myeloma cells and their strong stimulating capacity in 'one-way' mixed lymphocyte reaction: a comparative study with leukaemic B lymphoid cells. Cultured human myeloma cells (ARH-77, RPMI-8226 and U-266), like leukaemic B lymphoid cells, consistently exerted a strong stimulating capacity on allogeneic lymphocytes in the 'one-way' mixed lymphocyte reaction. An optimal stimulation was seen when a 1:1 ratio or 1:2 ratio of responding cell:stimulating cells of each cell line was utilized. The stimulating capacity of ARH-77 or RPMI-8226 cells was significantly diminished when a 1:4 ratio of responding cells:stimulating cells was utilized. Fresh bone marrow cells containing more than 80% plasma cells from a patient with multiple myeloma, on the other hand, failed to exert the stimulating capacity on two occasions. The striking difference between cultured myeloma cells and fresh plasma cells is that the Ia-like antigen is present on cultured myeloma cells, and this antigen is absent on fresh plasma cells. The relationship between the Ia-like antigen and the stimulating capacity in 'one-way' mixed lymphocyte reaction is discussed."} {"id": "PMID:159863", "title": "Restoration of impaired immune functions of aged animals by chronic bestatin treatment.", "content": "An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin.", "contents": "Restoration of impaired immune functions of aged animals by chronic bestatin treatment. An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin."} {"id": "PMID:159864", "title": "Rabbit anti-EL4 serum. A reagent with specificity for a population of murine suppressor cells.", "content": "Antisera against the C57B1 (H-2b) mouse lymphoma, EL4 were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressor function of Con A-stimulated splenic lymphocytes, but was unreactive against Con A-stimulated and allogeneically primed cytotoxic cells, or helper T cells. Consequently, heteroantiserum against EL4 may provide a useful reagent for the differentiation of cytotoxic from suppressor T-cell subsets.", "contents": "Rabbit anti-EL4 serum. A reagent with specificity for a population of murine suppressor cells. Antisera against the C57B1 (H-2b) mouse lymphoma, EL4 were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressor function of Con A-stimulated splenic lymphocytes, but was unreactive against Con A-stimulated and allogeneically primed cytotoxic cells, or helper T cells. Consequently, heteroantiserum against EL4 may provide a useful reagent for the differentiation of cytotoxic from suppressor T-cell subsets."} {"id": "PMID:159877", "title": "[Paralytic abdominal hernia in zoster].", "content": "In a 56 year old patient with zoster in the thoracic segments 10 and 11 an abdominal hernia developed. The hernia was caused by peripheral motorial paresis.", "contents": "[Paralytic abdominal hernia in zoster]. In a 56 year old patient with zoster in the thoracic segments 10 and 11 an abdominal hernia developed. The hernia was caused by peripheral motorial paresis."} {"id": "PMID:159878", "title": "[Acne fulminans].", "content": "Acne fulminans is a rare disorder of male teenage patients. The disease is characterized by the sudden appearance of highly inflammatory, tender, ulcerative and crusted lesions on back, chest and face. At the onset of the disease all patients show febrile temperature, leucocytosis, increased sedimentation rate and frequently polyarthralgia. The reported case showed typical lesions and distribution, fever, leucocytosis, elevated sedimentation rate, anemia, a decrease in albumin and an increase in alpha 2-globulin. Intradermal skin tests (delayed reactivity) showed marked decrease responses. Systemic treatment with antibiotics (ampicilline, tetracycline) with concomitant topical therapy was effective.", "contents": "[Acne fulminans]. Acne fulminans is a rare disorder of male teenage patients. The disease is characterized by the sudden appearance of highly inflammatory, tender, ulcerative and crusted lesions on back, chest and face. At the onset of the disease all patients show febrile temperature, leucocytosis, increased sedimentation rate and frequently polyarthralgia. The reported case showed typical lesions and distribution, fever, leucocytosis, elevated sedimentation rate, anemia, a decrease in albumin and an increase in alpha 2-globulin. Intradermal skin tests (delayed reactivity) showed marked decrease responses. Systemic treatment with antibiotics (ampicilline, tetracycline) with concomitant topical therapy was effective."} {"id": "PMID:159880", "title": "On the heterogeneity of capillaries of pigeon pectoralis muscle: a histoenzymatic and ultrastructural study.", "content": "Earlier studies had failed to show the presence of capillaries between the white fibres of pigeon pectoralis muscle. In this paper, data are reported for the first time documenting that these capillaries occur in both intra- and inter-fasicular areas of the muscle. Fresh frozen sections of pigeon pectoralis major muscle were incubated for alkaline ATPase reaction following pretreatment with different EDTA solutions (4.3 mM, pH 4.3). The results showed the existence of an inherent heterogeneity of capillaries. The capillaries of white fibres stained intensely for K+/Mg2+-EDTA or Mg2+-EDTA pre-incubated ATPase; the capillaries of red fibres stained poorly. Both white fibre and red fibre capillaries were examined ultrastructurally in the non-perfused pigeon pectoralis muscle. It is suggested that a possible correlation exists between the distinctive metabolic and mechanical characteristics of the Type II white, glycolytic, fast-twitch fast-fatigue muscle fibres and the high ATPase activity of their capillaries.", "contents": "On the heterogeneity of capillaries of pigeon pectoralis muscle: a histoenzymatic and ultrastructural study. Earlier studies had failed to show the presence of capillaries between the white fibres of pigeon pectoralis muscle. In this paper, data are reported for the first time documenting that these capillaries occur in both intra- and inter-fasicular areas of the muscle. Fresh frozen sections of pigeon pectoralis major muscle were incubated for alkaline ATPase reaction following pretreatment with different EDTA solutions (4.3 mM, pH 4.3). The results showed the existence of an inherent heterogeneity of capillaries. The capillaries of white fibres stained intensely for K+/Mg2+-EDTA or Mg2+-EDTA pre-incubated ATPase; the capillaries of red fibres stained poorly. Both white fibre and red fibre capillaries were examined ultrastructurally in the non-perfused pigeon pectoralis muscle. It is suggested that a possible correlation exists between the distinctive metabolic and mechanical characteristics of the Type II white, glycolytic, fast-twitch fast-fatigue muscle fibres and the high ATPase activity of their capillaries."} {"id": "PMID:159881", "title": "The ultrastructural localization of membrane ATPase in rat thin limbs of the loop of Henle.", "content": "The cytochemical distribution of nonspecific membrane ATPase activity in the epithelial membranes of the thin limbs of the loops of Henle of rat nephrons was studied at the ultrastructural level. Membrane ATPase activity was localized in the luminal, lateral, and (to a lesser extent) basal membranes of only the outer medullary segment of the thin descending limbs of long nephrons (Type II epithelium). The reaction product was lacking in the thin limb of short nephrons (Type I epithelium) as well as in the inner medullary descending (Type III epithelium) and ascending (Type IV epithelium) segments of the thin limbs of long nephrons. These data reinforce the concept of thin limb heterogeneity and may indicate a specialized role for the outer medullary segment of thin descending limbs of long nephrons in the concentrating mechanism.", "contents": "The ultrastructural localization of membrane ATPase in rat thin limbs of the loop of Henle. The cytochemical distribution of nonspecific membrane ATPase activity in the epithelial membranes of the thin limbs of the loops of Henle of rat nephrons was studied at the ultrastructural level. Membrane ATPase activity was localized in the luminal, lateral, and (to a lesser extent) basal membranes of only the outer medullary segment of the thin descending limbs of long nephrons (Type II epithelium). The reaction product was lacking in the thin limb of short nephrons (Type I epithelium) as well as in the inner medullary descending (Type III epithelium) and ascending (Type IV epithelium) segments of the thin limbs of long nephrons. These data reinforce the concept of thin limb heterogeneity and may indicate a specialized role for the outer medullary segment of thin descending limbs of long nephrons in the concentrating mechanism."} {"id": "PMID:159882", "title": "Histochemical characteristics of a tonic smooth muscle.", "content": "It is suggested that ABRM, smooth muscle of Mytilus edulis L. and Mytilus galloprovincialis Lmk. (Mollusca Pelecypoda), is composed of one histochemical fibre type. The fibres are characterized by a low myofibrillar ATPase activity. Succinic and nicotinamide adenine dinucleotide oxidoreductase activities are distributed in a reverse pattern than that of the ATPase activity. Glycogen phosphorylase is richly represented in ABRM fibres and this detection is in opposition with the negative detection of alkaline phosphatase activity. These preliminary histochemical observations are similar to those found in some vertebrate smooth muscles. Mitochondrial glycerol-3-phosphate, 6-phosphogluconate, lactate and octopine dehydrogenases are not detected in muscle fibres whereas glio-interstitial tissues show weak but distinct reactivity. These last results especially characterize Mytilus catch fibres and are briefly discussed in relationship with previous physiological, biochemical and morphological observations.", "contents": "Histochemical characteristics of a tonic smooth muscle. It is suggested that ABRM, smooth muscle of Mytilus edulis L. and Mytilus galloprovincialis Lmk. (Mollusca Pelecypoda), is composed of one histochemical fibre type. The fibres are characterized by a low myofibrillar ATPase activity. Succinic and nicotinamide adenine dinucleotide oxidoreductase activities are distributed in a reverse pattern than that of the ATPase activity. Glycogen phosphorylase is richly represented in ABRM fibres and this detection is in opposition with the negative detection of alkaline phosphatase activity. These preliminary histochemical observations are similar to those found in some vertebrate smooth muscles. Mitochondrial glycerol-3-phosphate, 6-phosphogluconate, lactate and octopine dehydrogenases are not detected in muscle fibres whereas glio-interstitial tissues show weak but distinct reactivity. These last results especially characterize Mytilus catch fibres and are briefly discussed in relationship with previous physiological, biochemical and morphological observations."} {"id": "PMID:159885", "title": "Volume-displacement body plethysmograph using a large flowmeter without pressure compensation.", "content": "A modification of the conventional volume-displacement whole-body plethysmograph was done using a low-resistance flow element and integrating the plethysmographic pressure signal. A flow element with a resistance of 0.036 cmH2O/(l/s), linear to 75 l/s was fitted to a 440-liter plethysmograph, resulting in an instrument with a volume-amplitude-frequency response flat to 15 Hz and in phase with mouth flow and esophageal catheter-balloon to at least 15 Hz without pressure compensation.", "contents": "Volume-displacement body plethysmograph using a large flowmeter without pressure compensation. A modification of the conventional volume-displacement whole-body plethysmograph was done using a low-resistance flow element and integrating the plethysmographic pressure signal. A flow element with a resistance of 0.036 cmH2O/(l/s), linear to 75 l/s was fitted to a 440-liter plethysmograph, resulting in an instrument with a volume-amplitude-frequency response flat to 15 Hz and in phase with mouth flow and esophageal catheter-balloon to at least 15 Hz without pressure compensation."} {"id": "PMID:159886", "title": "Evaluation of a hot-wire respiratory flowmeter for clinical applicability.", "content": "A hot-wire flowmeter was evaluated for clinical applicability. 1) Calibration with a syringe could be done if emptying duration was 1-15 s. 2) Outputs linearly decreased with decreasing concentration of N2 in O2. Outputs with CO2 in O2 and N2O in O2 represented nonlinear convex relationships with varying concentrations of CO2 and N2O. Correction for each gas mixture to be measured is required. 3) Outputs linearly decreased with decreasing barometric pressure. 4) Stability assessed with a piston respirator was excellent (within +/- 2% of syringe volume) after 15 min warmup time. However, daily calibrations are recommended in clinical situations. 5) Nebulization, if not excessive, was acceptable if the expired gas was measured at the mouth. 6) Hot-wire burning, which occurred when it was partially in contact with materials whose specific heat differed with air, was successfully protected with a simple shutoff circuit. 7) The possibility of producing nitrogen oxides by the catalytic action of the platinum hot-wire was denied by colorimetric determination. Interchangeability and sterilizability of transducers and improved mechanical strength with platinum-rhodium alloy are also discussed.", "contents": "Evaluation of a hot-wire respiratory flowmeter for clinical applicability. A hot-wire flowmeter was evaluated for clinical applicability. 1) Calibration with a syringe could be done if emptying duration was 1-15 s. 2) Outputs linearly decreased with decreasing concentration of N2 in O2. Outputs with CO2 in O2 and N2O in O2 represented nonlinear convex relationships with varying concentrations of CO2 and N2O. Correction for each gas mixture to be measured is required. 3) Outputs linearly decreased with decreasing barometric pressure. 4) Stability assessed with a piston respirator was excellent (within +/- 2% of syringe volume) after 15 min warmup time. However, daily calibrations are recommended in clinical situations. 5) Nebulization, if not excessive, was acceptable if the expired gas was measured at the mouth. 6) Hot-wire burning, which occurred when it was partially in contact with materials whose specific heat differed with air, was successfully protected with a simple shutoff circuit. 7) The possibility of producing nitrogen oxides by the catalytic action of the platinum hot-wire was denied by colorimetric determination. Interchangeability and sterilizability of transducers and improved mechanical strength with platinum-rhodium alloy are also discussed."} {"id": "PMID:159887", "title": "Effect of Sindbis birus infection on survival of mice in the cold.", "content": "Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold.", "contents": "Effect of Sindbis birus infection on survival of mice in the cold. Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold."} {"id": "PMID:159903", "title": "Myosin from striated adductor muscle of Chlamys nipponensis akazara.", "content": "Myosin was isolated from striated adductor muscle of Akazara shell-fish, and purified on DEAE-Sephadex A50. The sedimentation constant (s 20,2 0 W) and the intrinsic viscosity, [eta] of Akazara myosin thus purified were estimated to be 6.6 S and 2.10 dl/g, respectively. In many respects, Akazara myosin was similar to scallop myosin. (1) Only one size of light-chain component (17,000 daltons) was detectable in SDS-gel electrophoresis of Akazara myosin, but two types of light-chain component were seen in urea-gel electrophoresis; these were equivalent to EDTA-light chain and SH-light chain of scallop myosin. The molar ratio of heavy chain (206,000 daltons), EDTA-light chain, and SH-light chain in Akazara myosin was estimated, from the staining densities of gel-electrophoretic bands, to be approximately 1 : 1 : 1. (2) EDTA-washing procedure removed EDTA-light chain only, causing desensitization of Akazara myosin. EDTA-light chain isolated from Akazara myofibrils was able to resensitize EDTA-washed Akazara myosin. Akazara myosin, however, was found to be different from scallop myosin in two important properties: (1) complete removal of EDTA-light chains was required to achieve a complete loss of calcium sensitivity, and full resensitization was attained on recombination of EDTA-light chains with desensitized myosin prepared essentially free from EDTA-light chains. (2) EDTA-light chains isolated from Akazara myofibrils show a calcium-induced UV absorption difference spectrum.", "contents": "Myosin from striated adductor muscle of Chlamys nipponensis akazara. Myosin was isolated from striated adductor muscle of Akazara shell-fish, and purified on DEAE-Sephadex A50. The sedimentation constant (s 20,2 0 W) and the intrinsic viscosity, [eta] of Akazara myosin thus purified were estimated to be 6.6 S and 2.10 dl/g, respectively. In many respects, Akazara myosin was similar to scallop myosin. (1) Only one size of light-chain component (17,000 daltons) was detectable in SDS-gel electrophoresis of Akazara myosin, but two types of light-chain component were seen in urea-gel electrophoresis; these were equivalent to EDTA-light chain and SH-light chain of scallop myosin. The molar ratio of heavy chain (206,000 daltons), EDTA-light chain, and SH-light chain in Akazara myosin was estimated, from the staining densities of gel-electrophoretic bands, to be approximately 1 : 1 : 1. (2) EDTA-washing procedure removed EDTA-light chain only, causing desensitization of Akazara myosin. EDTA-light chain isolated from Akazara myofibrils was able to resensitize EDTA-washed Akazara myosin. Akazara myosin, however, was found to be different from scallop myosin in two important properties: (1) complete removal of EDTA-light chains was required to achieve a complete loss of calcium sensitivity, and full resensitization was attained on recombination of EDTA-light chains with desensitized myosin prepared essentially free from EDTA-light chains. (2) EDTA-light chains isolated from Akazara myofibrils show a calcium-induced UV absorption difference spectrum."} {"id": "PMID:159904", "title": "Reversible effects of fatty acids on respiration, oxidative phosphorylation, and heat production of rat liver mitochondria.", "content": "1. Oleic acid at low concentrations (0--70 nmol/mg protein) stimulated mitochondrial state 4 respiration 4-fold, increased the apparent enthalpy change of the respiration per gram atom of oxygen consumed from -112 to -208 kJ/O and completely inhibited ATP synthesis without significant effect on the Mg-ATPase activity of mitochondria. 2. Similar effects on mitochondrial respiratory activities were observed with other fatty acids. 3. Bovine serum albumin (BSA) protected mitochondria from the effects of oleic acid irrespective of the order of addition of oleic acid and BSA to mitochondria. The capacity of BSA to bind oleic acid was calculated to be 3.6--7.1 (mean, 4.9) mol of oleic acid/mol of BSA. 4. The response time of mitochondrial respiration to added oleic acid or BSA was 20--25 s.", "contents": "Reversible effects of fatty acids on respiration, oxidative phosphorylation, and heat production of rat liver mitochondria. 1. Oleic acid at low concentrations (0--70 nmol/mg protein) stimulated mitochondrial state 4 respiration 4-fold, increased the apparent enthalpy change of the respiration per gram atom of oxygen consumed from -112 to -208 kJ/O and completely inhibited ATP synthesis without significant effect on the Mg-ATPase activity of mitochondria. 2. Similar effects on mitochondrial respiratory activities were observed with other fatty acids. 3. Bovine serum albumin (BSA) protected mitochondria from the effects of oleic acid irrespective of the order of addition of oleic acid and BSA to mitochondria. The capacity of BSA to bind oleic acid was calculated to be 3.6--7.1 (mean, 4.9) mol of oleic acid/mol of BSA. 4. The response time of mitochondrial respiration to added oleic acid or BSA was 20--25 s."} {"id": "PMID:159905", "title": "Modification of cardiac and smooth muscle myosins with 2,4,6-trinitrobenzenesulfonate. Evidence for differences in structure around the active sites of cardiac, smooth, and skeletal muscle myosin ATPase.", "content": "Myosins purified from cardiac (porcine heart) and smooth (chicken gizzard) muscles were modified with 2,4,6-trinitrobenzenesulfonate (TNBS) and the effects on the kinetic properties of myosin ATPase [EC 3.6.1.3] were studied. The following results were obtained. 1. About 0.5 mol of TNBS per mol of myosin head was incorporated rapidly, irrespective of the presence of PP1 (2mM), into both types of myosin studied. 2. The size of the initial burst of P1 liberation for both myosins was found to be 0.5--0.6 mol/mol head. 3. The rapid incorporation of TNBS into cardiac muscle myosin was accompanied by a rapid decrease in the size of the initial P1 burst, and it was completely lost after modification for 20 min. However, smooth muscle myosin retained its P1 burst. 4. The EDTA (K+)-ATPase activity of both myosins modified in the presence or absence of PP1 decreased sharply with incorporation of TNBS. 5. Superprecipitation and ATPase activity of reconstituted actomyosin from cardiac myosin and skeletal F-actin decreased only after 10 min of modification with TNBS in the absence of PP1. 6. The spectra of TNP bound to myosins from cardiac and smooth muscles were unchanged by the addition of PP1. The above findings are compared with those previously obtained for skeletal muscle myosin [Miyanishi, T., Inoue, A., & Tonomura, Y. (1979) J. Biochem. 85, 747--753], and the structural and functional differences among the myosins derived from skeletal, cardiac, and smooth muscles are discussed.", "contents": "Modification of cardiac and smooth muscle myosins with 2,4,6-trinitrobenzenesulfonate. Evidence for differences in structure around the active sites of cardiac, smooth, and skeletal muscle myosin ATPase. Myosins purified from cardiac (porcine heart) and smooth (chicken gizzard) muscles were modified with 2,4,6-trinitrobenzenesulfonate (TNBS) and the effects on the kinetic properties of myosin ATPase [EC 3.6.1.3] were studied. The following results were obtained. 1. About 0.5 mol of TNBS per mol of myosin head was incorporated rapidly, irrespective of the presence of PP1 (2mM), into both types of myosin studied. 2. The size of the initial burst of P1 liberation for both myosins was found to be 0.5--0.6 mol/mol head. 3. The rapid incorporation of TNBS into cardiac muscle myosin was accompanied by a rapid decrease in the size of the initial P1 burst, and it was completely lost after modification for 20 min. However, smooth muscle myosin retained its P1 burst. 4. The EDTA (K+)-ATPase activity of both myosins modified in the presence or absence of PP1 decreased sharply with incorporation of TNBS. 5. Superprecipitation and ATPase activity of reconstituted actomyosin from cardiac myosin and skeletal F-actin decreased only after 10 min of modification with TNBS in the absence of PP1. 6. The spectra of TNP bound to myosins from cardiac and smooth muscles were unchanged by the addition of PP1. The above findings are compared with those previously obtained for skeletal muscle myosin [Miyanishi, T., Inoue, A., & Tonomura, Y. (1979) J. Biochem. 85, 747--753], and the structural and functional differences among the myosins derived from skeletal, cardiac, and smooth muscles are discussed."} {"id": "PMID:159906", "title": "In vitro and in vivo evaluations of dacron velour and knit prostheses.", "content": "Dacron velour and knit prostheses were compared with respect to long-term patency when used as canine aortic implants. These grafts were rated, according to the average numerical value of six equally weighted criteria, in decreasing order of performance: velour I, velour II, circular knit III, velour IV, circular knit V, warp-knit VI, warp-knit VII and VIII, warp-knit IX and warp-knit X. In general, compacting and crimping methods using halogenated hydrocarbons produced the least successful grafts. Grafts of identical brand but compacted and crimped by different methods exhibited different patencies. No true healing of the grafts was observed. Layered deposits of inner fibrous capsule were formed at rates and thicknesses characteristic for each type of graft employed. A functioning Dacron femoral-popliteal bypass removed from a human after 9 months exhibited inner and outer fibrous capsules similar to those from canine implants.", "contents": "In vitro and in vivo evaluations of dacron velour and knit prostheses. Dacron velour and knit prostheses were compared with respect to long-term patency when used as canine aortic implants. These grafts were rated, according to the average numerical value of six equally weighted criteria, in decreasing order of performance: velour I, velour II, circular knit III, velour IV, circular knit V, warp-knit VI, warp-knit VII and VIII, warp-knit IX and warp-knit X. In general, compacting and crimping methods using halogenated hydrocarbons produced the least successful grafts. Grafts of identical brand but compacted and crimped by different methods exhibited different patencies. No true healing of the grafts was observed. Layered deposits of inner fibrous capsule were formed at rates and thicknesses characteristic for each type of graft employed. A functioning Dacron femoral-popliteal bypass removed from a human after 9 months exhibited inner and outer fibrous capsules similar to those from canine implants."} {"id": "PMID:159907", "title": "Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.", "content": "The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation.", "contents": "Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border. The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation."} {"id": "PMID:159908", "title": "alpha-Amanitin and 5-fluorouridine inhibition of serum-stimulated DNA synthesis in quiescent AKR-2B mouse embryo cells.", "content": "AKR-2B mouse embryo cells undergoing the serum-stimulated transition from a quiescent to a proliferating state exhibit an increase in the rate of hnRNA synthesis which appears to be mediated through an increase in the actual number of RNA polymerase II molecules. alpha-Amanitin, administered early in the prereplication interval following stimulation, effectively inhibits hnRNA synthesis, polysomal mRNA accumulation, polyribosome formation, and subsequent DNA synthesis, and cell division. Unexpectedly, alpha-amanitin treatment also produces almost complete inhibition of the synthesis of 45S rRNA precursor and the increase in accumulation of cytoplasmic rRNA following serum stimulation. In order to determine whether the inhibition of new ribosomal synthesis might in itself be sufficient to prevent serum-stimulated DNA synthesis, the effects of 5-fluorouridine (5-FU), a specific inhibitor of 45S rRNA processing, were investigated. If added within eight hours following serum stimulation, 5-FU was found to completely inhibit subsequent DNA synthesis. These results suggest that quiescent AKR-2B cells do not contain a sufficient excess of ribosomes to support the synthesis of proteins which are required for DNA synthesis in response to serum growth factors. Furthermore, an early polymerase II mediated synthesis of mRNA(s) coding for some factor(s) necessary for ribosomal gene transcription may be an essential step in the serum-stimulated synthesis of new ribosomes.", "contents": "alpha-Amanitin and 5-fluorouridine inhibition of serum-stimulated DNA synthesis in quiescent AKR-2B mouse embryo cells. AKR-2B mouse embryo cells undergoing the serum-stimulated transition from a quiescent to a proliferating state exhibit an increase in the rate of hnRNA synthesis which appears to be mediated through an increase in the actual number of RNA polymerase II molecules. alpha-Amanitin, administered early in the prereplication interval following stimulation, effectively inhibits hnRNA synthesis, polysomal mRNA accumulation, polyribosome formation, and subsequent DNA synthesis, and cell division. Unexpectedly, alpha-amanitin treatment also produces almost complete inhibition of the synthesis of 45S rRNA precursor and the increase in accumulation of cytoplasmic rRNA following serum stimulation. In order to determine whether the inhibition of new ribosomal synthesis might in itself be sufficient to prevent serum-stimulated DNA synthesis, the effects of 5-fluorouridine (5-FU), a specific inhibitor of 45S rRNA processing, were investigated. If added within eight hours following serum stimulation, 5-FU was found to completely inhibit subsequent DNA synthesis. These results suggest that quiescent AKR-2B cells do not contain a sufficient excess of ribosomes to support the synthesis of proteins which are required for DNA synthesis in response to serum growth factors. Furthermore, an early polymerase II mediated synthesis of mRNA(s) coding for some factor(s) necessary for ribosomal gene transcription may be an essential step in the serum-stimulated synthesis of new ribosomes."} {"id": "PMID:159910", "title": "Predicting pain treatment results by personality variables in organic and functional patients.", "content": "Recent literature has suggested that the traditional dichotomy of organic vs. functional classification for pain patients is unimportant in determining the role of personality variables in predicting treatment outcome. The present study examined the role of MMPI variables in predicting treatment outcome in pain patients with definitive physical disorders (N = 58) (organic) and in patients without definitive physical findings (N = 46) (functional). In the organic group, the presence of high Hs was associated with poor outcome, while in the functional group K scores were associated with poor outcome. Results suggested that although personality variables played an equal role in both groups, the nature of that contribution may vary in the functional and organic groups.", "contents": "Predicting pain treatment results by personality variables in organic and functional patients. Recent literature has suggested that the traditional dichotomy of organic vs. functional classification for pain patients is unimportant in determining the role of personality variables in predicting treatment outcome. The present study examined the role of MMPI variables in predicting treatment outcome in pain patients with definitive physical disorders (N = 58) (organic) and in patients without definitive physical findings (N = 46) (functional). In the organic group, the presence of high Hs was associated with poor outcome, while in the functional group K scores were associated with poor outcome. Results suggested that although personality variables played an equal role in both groups, the nature of that contribution may vary in the functional and organic groups."} {"id": "PMID:159911", "title": "Circulating and deposited immune complexes in renal disease and their clinical correlation.", "content": "In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies of circulating immune complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients.", "contents": "Circulating and deposited immune complexes in renal disease and their clinical correlation. In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies of circulating immune complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients."} {"id": "PMID:159913", "title": "The allopurinol hypersensitivity syndrome.", "content": "Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Of thirty-eight patients reviewed herein (including seven from our hospital and thirty-one from a review of the literature), ten deaths (26%) were related to complications of allopurinol hypersensitivity. Preexisting renal disease was present in 97% of patients, and, in the majority of these, the dosage of allopurinol was not reduced despite instructions contained in the package insert for this drug. At least 78% of patients were taking a thiazide diuretic prior to starting allopurinol therapy. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. Other involvement such as gastrointestinal bleeding is common. The mechanism of the hypersensitivity reaction is not clear, but it may represent an immune complex disease prolonged by the persistence of a currently undefined antigen. Treatment with systemic corticosteroids, often for several months, is usually necessary for the gradual resolution of this potentially fatal syndrome.", "contents": "The allopurinol hypersensitivity syndrome. Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Of thirty-eight patients reviewed herein (including seven from our hospital and thirty-one from a review of the literature), ten deaths (26%) were related to complications of allopurinol hypersensitivity. Preexisting renal disease was present in 97% of patients, and, in the majority of these, the dosage of allopurinol was not reduced despite instructions contained in the package insert for this drug. At least 78% of patients were taking a thiazide diuretic prior to starting allopurinol therapy. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. Other involvement such as gastrointestinal bleeding is common. The mechanism of the hypersensitivity reaction is not clear, but it may represent an immune complex disease prolonged by the persistence of a currently undefined antigen. Treatment with systemic corticosteroids, often for several months, is usually necessary for the gradual resolution of this potentially fatal syndrome."} {"id": "PMID:159915", "title": "Statistical relationship of morsal to bucco-lingual, approximal and sulcal caries in rats.", "content": "The correlation of morsal with sulcal, bucco-lingual and approximal caries scores of rats was compared. The morsal with bucco-lingual plus approximal correlation was significantly better than the morsal with sulcal correlation. When reporting rat caries, sulcal scores should be reported alone; morsal scores should be grouped with bucco-lingual and approximal to demonstrate total smooth surface lesions.", "contents": "Statistical relationship of morsal to bucco-lingual, approximal and sulcal caries in rats. The correlation of morsal with sulcal, bucco-lingual and approximal caries scores of rats was compared. The morsal with bucco-lingual plus approximal correlation was significantly better than the morsal with sulcal correlation. When reporting rat caries, sulcal scores should be reported alone; morsal scores should be grouped with bucco-lingual and approximal to demonstrate total smooth surface lesions."} {"id": "PMID:159916", "title": "Undergraduate clinical pedodontic education: an overview of two teaching systems.", "content": "This paper compares and contrasts two clinical teaching systems in undergraduate pedodontics: the block system and the total patient care system (TPC). Descriptions and rationales are given for specific block and TPC systems at two universities. Theoretical advantages and disadvantages are reviewed. Clinical data are presented that represent experiences of the graduating classes of 1978 at The University of Iowa (block) and the University of North Carolina (TPC). From this limited sample there appears to be little quantitative evidence that one system is better than the other when examining clinical experiences in the two schools studied.", "contents": "Undergraduate clinical pedodontic education: an overview of two teaching systems. This paper compares and contrasts two clinical teaching systems in undergraduate pedodontics: the block system and the total patient care system (TPC). Descriptions and rationales are given for specific block and TPC systems at two universities. Theoretical advantages and disadvantages are reviewed. Clinical data are presented that represent experiences of the graduating classes of 1978 at The University of Iowa (block) and the University of North Carolina (TPC). From this limited sample there appears to be little quantitative evidence that one system is better than the other when examining clinical experiences in the two schools studied."} {"id": "PMID:159917", "title": "Encoding voice fundamental frequency into vibrotactile frequency.", "content": "Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency.", "contents": "Encoding voice fundamental frequency into vibrotactile frequency. Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency."} {"id": "PMID:159920", "title": "Nonspecific suppressor cell function in atopic subjects.", "content": "The status of concanavalin A (Con A)--nonspecific suppressor cell function and histamine-receptor--carrying mononuclear cells in 19 allergic and 27 nonallergic individuals was investigated. No differences were detected between the two groups with respect to suppression by Con A--activated suppressor cells of polyvalent Ig biosynthesis, IgG secretion, or mitogen-induced proliferative responses. Histamine-receptor--carrying cells of the allergic subjects were numerically equal to those of the nonallergic subjects. Mononuclear cells from the allergic group, however, required a higher dose of histamine than did those for the nonallergic group to induce suppression in vitro (p less than 0.02 for 10(-4) M histamine and p less than 0.05 for 10(-3) M histamine). Plasma from the allergic group contained higher levels of histamine activity (p less than 0.05). Plasma from either allergic or normal groups did not affect histamine activity in vitro. There are no apparent functional abnormalities of antigen-nonspecific mononuclear cells in the allergic patients with respect to non--IgE-mediated in vitro parameters. The demonstrated dysfunction of histamine-receptor--carrying cells could be attributed to high levels of circulating histamine that could result in receptor modulation in vivo. More work is needed to clarify the status of antigen-nonspecific and antigen-specific suppressor cells that regulate IgE biosynthesis in allergic states.", "contents": "Nonspecific suppressor cell function in atopic subjects. The status of concanavalin A (Con A)--nonspecific suppressor cell function and histamine-receptor--carrying mononuclear cells in 19 allergic and 27 nonallergic individuals was investigated. No differences were detected between the two groups with respect to suppression by Con A--activated suppressor cells of polyvalent Ig biosynthesis, IgG secretion, or mitogen-induced proliferative responses. Histamine-receptor--carrying cells of the allergic subjects were numerically equal to those of the nonallergic subjects. Mononuclear cells from the allergic group, however, required a higher dose of histamine than did those for the nonallergic group to induce suppression in vitro (p less than 0.02 for 10(-4) M histamine and p less than 0.05 for 10(-3) M histamine). Plasma from the allergic group contained higher levels of histamine activity (p less than 0.05). Plasma from either allergic or normal groups did not affect histamine activity in vitro. There are no apparent functional abnormalities of antigen-nonspecific mononuclear cells in the allergic patients with respect to non--IgE-mediated in vitro parameters. The demonstrated dysfunction of histamine-receptor--carrying cells could be attributed to high levels of circulating histamine that could result in receptor modulation in vivo. More work is needed to clarify the status of antigen-nonspecific and antigen-specific suppressor cells that regulate IgE biosynthesis in allergic states."} {"id": "PMID:159921", "title": "Topical fluorouracil therapy for precancers and cancers of the skin.", "content": "Topical fluorouracil (FU) is an extremely effective agent for treating multiple actinic keratoses. It is also of value in the treatment of Bowen's disease, actinic cheilitis, arsenical keratoses, radiodermatitis, X-ray-induced keratoses, leukoplakia, and the erythroplasia of Queyrat. Topical FU may be successful in the treatment of superficial basal-cell carcinomas, but should not be used for nodular carcinomas of the face or neck except under unusual circumstances and with mandatory histologic follow-up evaluation. The usual method of treatment is twice daily application of a 1 percent FU solution in propylene glycol. Several modifications of various types of commonly employed preparations and the manner in which each is used are described, along with the respective indications. The considerable discomfort associated with the use of topical FU can be lessened by the stepwise approach outlined--a method extraordinarily valuable for older patients. Occasional complications are primary irritant dermatitis and allergic contact dermatitis; these must be recognized promptly and treated, as must other less frequent side effects. Topical FU appears to be of great value in the destruction of existing precancerous skin lesions. When used repeatedly, it may postpone indefinitely the development of significant precancerous and cancerous skin lesions.", "contents": "Topical fluorouracil therapy for precancers and cancers of the skin. Topical fluorouracil (FU) is an extremely effective agent for treating multiple actinic keratoses. It is also of value in the treatment of Bowen's disease, actinic cheilitis, arsenical keratoses, radiodermatitis, X-ray-induced keratoses, leukoplakia, and the erythroplasia of Queyrat. Topical FU may be successful in the treatment of superficial basal-cell carcinomas, but should not be used for nodular carcinomas of the face or neck except under unusual circumstances and with mandatory histologic follow-up evaluation. The usual method of treatment is twice daily application of a 1 percent FU solution in propylene glycol. Several modifications of various types of commonly employed preparations and the manner in which each is used are described, along with the respective indications. The considerable discomfort associated with the use of topical FU can be lessened by the stepwise approach outlined--a method extraordinarily valuable for older patients. Occasional complications are primary irritant dermatitis and allergic contact dermatitis; these must be recognized promptly and treated, as must other less frequent side effects. Topical FU appears to be of great value in the destruction of existing precancerous skin lesions. When used repeatedly, it may postpone indefinitely the development of significant precancerous and cancerous skin lesions."} {"id": "PMID:159922", "title": "The effects of estrogen treatment of carcinoma of the prostate on regional adipocyte size.", "content": "Fat cell size was determined in the gluteal, femoral and hypogastric regions of subcutaneous adipose tissue in men with carcinoma of the prostate before and after 5--6 months of estrogen treatment. Body weight and several metabolic variables did not change. Gluteal fat cell size increased. It was suggested that increase of the gluteal fat cell size is a characteristic effect of estrogens on adipose tissue because a similar increase has been previously found in young women in comparison with young men.", "contents": "The effects of estrogen treatment of carcinoma of the prostate on regional adipocyte size. Fat cell size was determined in the gluteal, femoral and hypogastric regions of subcutaneous adipose tissue in men with carcinoma of the prostate before and after 5--6 months of estrogen treatment. Body weight and several metabolic variables did not change. Gluteal fat cell size increased. It was suggested that increase of the gluteal fat cell size is a characteristic effect of estrogens on adipose tissue because a similar increase has been previously found in young women in comparison with young men."} {"id": "PMID:159923", "title": "Biomechanical evaluation of metacarpophalangeal joint prosthesis designs.", "content": "A laboratory biomechanical analysis of metacarpophalangeal joint prosthesis designs was done with fresh cadaver finger rays. The center of rotation, range of motion, tendon excursion, and fingertip force were determined on the specimens before and after implanting Swanson, Niebauer, Steffee II, St. Georg-Buchholz, Schultz, and modified Strickland prostheses. Their biomechanical behavior varied considerably and none duplicated the normal metacarpophalangeal (MP) joint. Each has design characteristics that may be clinically advantageous as well as disadvantageous. Irrespective of the design, the studies done cannot be divorced from the following factors: (1) implant material properties--silicone rubber implants buckled with tendon loading; this deformity created a significant flexor mechanical advantage and an extensor mechanical disadvantage; (2) implant fixation--freely movable implant stems dampened part of the applied load; braided suture provided inadequate immediate fixation; (3) implantation technique--the articulated prostheses can be technically unforgiving; errors in technique resulted in alteration of their biomechanical behavior.", "contents": "Biomechanical evaluation of metacarpophalangeal joint prosthesis designs. A laboratory biomechanical analysis of metacarpophalangeal joint prosthesis designs was done with fresh cadaver finger rays. The center of rotation, range of motion, tendon excursion, and fingertip force were determined on the specimens before and after implanting Swanson, Niebauer, Steffee II, St. Georg-Buchholz, Schultz, and modified Strickland prostheses. Their biomechanical behavior varied considerably and none duplicated the normal metacarpophalangeal (MP) joint. Each has design characteristics that may be clinically advantageous as well as disadvantageous. Irrespective of the design, the studies done cannot be divorced from the following factors: (1) implant material properties--silicone rubber implants buckled with tendon loading; this deformity created a significant flexor mechanical advantage and an extensor mechanical disadvantage; (2) implant fixation--freely movable implant stems dampened part of the applied load; braided suture provided inadequate immediate fixation; (3) implantation technique--the articulated prostheses can be technically unforgiving; errors in technique resulted in alteration of their biomechanical behavior."} {"id": "PMID:159924", "title": "Staphylococcal sepsis in a burns unit.", "content": "An outbreak of staphylococcal sepsis in a burns unit occurred between January 1976 and May 1978. Many patients and members of staff had boils, and a number of patients also developed septicaemia. Most of the boils in the early period of the trial and a large proportion of boils in patients during the later period yielded Staphylococcus aureus resistant to penicillin, tetracycline and erythromycin only (PTE), and were shown to be of phage type 95 in the early period while strains were phage typed. From blood cultures, most strains in the early period were of resistance pattern PTE and phage type 95, but in the later period other resistance patterns were predominant. Strains from burns were usually multiresistant (PTEKNML) and of the phage pattern 29/77, which had been endemic in the Unit, but during the early period of the outbreak there was an increased proportion of strains in burns with the resistance pattern PTE and of phage type 95. Staphylococcal sepsis has for many years been very infrequent in the burns unit. This outbreak seems to have been initiated by a strain of phage type 95 and resistance pattern PTE, but during the course of the outbreak the endemic strain of type 29/77 and some other staphylococci seem to have developed enhanced ability to cause clinical infections, conceivably by transduction from the epidemic strain of phage type 95.", "contents": "Staphylococcal sepsis in a burns unit. An outbreak of staphylococcal sepsis in a burns unit occurred between January 1976 and May 1978. Many patients and members of staff had boils, and a number of patients also developed septicaemia. Most of the boils in the early period of the trial and a large proportion of boils in patients during the later period yielded Staphylococcus aureus resistant to penicillin, tetracycline and erythromycin only (PTE), and were shown to be of phage type 95 in the early period while strains were phage typed. From blood cultures, most strains in the early period were of resistance pattern PTE and phage type 95, but in the later period other resistance patterns were predominant. Strains from burns were usually multiresistant (PTEKNML) and of the phage pattern 29/77, which had been endemic in the Unit, but during the early period of the outbreak there was an increased proportion of strains in burns with the resistance pattern PTE and of phage type 95. Staphylococcal sepsis has for many years been very infrequent in the burns unit. This outbreak seems to have been initiated by a strain of phage type 95 and resistance pattern PTE, but during the course of the outbreak the endemic strain of type 29/77 and some other staphylococci seem to have developed enhanced ability to cause clinical infections, conceivably by transduction from the epidemic strain of phage type 95."} {"id": "PMID:159925", "title": "Comparison of Staphylococcus aureus carriage and skin infection rates in hospital and office employees.", "content": "The incidence of Staphylococcus aureus in the nose, throat and superficial wound infections of 99 office staff, 129 psychiatry staff and 115 surgical staff was studied over a 4-week period with the purpose of assessing the potential risk to hospital personnel of staphylococcal infection. Incidence rates, both average and cumulative, were essentially similar in the three groups but certain differences in the ecology of the staphylococcal phage groups were observed. Surgical staff appeared to have a more labile pattern of carriage. As in other Scandinavian studies throat carriage rates were high. Staphylococcal carriage seems largely to depend on individual characteristics rather than environmental factors.", "contents": "Comparison of Staphylococcus aureus carriage and skin infection rates in hospital and office employees. The incidence of Staphylococcus aureus in the nose, throat and superficial wound infections of 99 office staff, 129 psychiatry staff and 115 surgical staff was studied over a 4-week period with the purpose of assessing the potential risk to hospital personnel of staphylococcal infection. Incidence rates, both average and cumulative, were essentially similar in the three groups but certain differences in the ecology of the staphylococcal phage groups were observed. Surgical staff appeared to have a more labile pattern of carriage. As in other Scandinavian studies throat carriage rates were high. Staphylococcal carriage seems largely to depend on individual characteristics rather than environmental factors."} {"id": "PMID:159926", "title": "A microculture technique for rat lymphocyte transformation.", "content": "We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.", "contents": "A microculture technique for rat lymphocyte transformation. We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described."} {"id": "PMID:159927", "title": "A newly designed whole microplate automatic harvester for lymphocyte stimulation assays.", "content": "A unique automated sampling manifold designed to recover cells grown in standard 96 well microplates from their culture medium is described. Cells are recovered and washed on fiber glass filter discs. Incorporation of radioisotopes into cells, can then be measured by appropriate counting of the filter discs. Typical applications include termination of mixed lymphocyte cultures, assays of mitogen stimulation of lymphocytes and antigen-specific lymphocyte transformation and assays of interferon activity. The harvester can also be used in other biological systems where collection and washing of precipitates is desired.", "contents": "A newly designed whole microplate automatic harvester for lymphocyte stimulation assays. A unique automated sampling manifold designed to recover cells grown in standard 96 well microplates from their culture medium is described. Cells are recovered and washed on fiber glass filter discs. Incorporation of radioisotopes into cells, can then be measured by appropriate counting of the filter discs. Typical applications include termination of mixed lymphocyte cultures, assays of mitogen stimulation of lymphocytes and antigen-specific lymphocyte transformation and assays of interferon activity. The harvester can also be used in other biological systems where collection and washing of precipitates is desired."} {"id": "PMID:159928", "title": "Mitogen-induced suppressor T cell activity in the in vitro cellular immune response.", "content": "A 24 h preincubation of human peripheral lymphocytes (PBL) in the presence of phytohemagglutinin (PHA) or concanavalin A (Con. A) renders them suppressive for the response of untreated cells to PHA, Con. A, candidin and allogeneic cells. However, cells stimulated with lipopolysaccharide (LPS) show no suppression.", "contents": "Mitogen-induced suppressor T cell activity in the in vitro cellular immune response. A 24 h preincubation of human peripheral lymphocytes (PBL) in the presence of phytohemagglutinin (PHA) or concanavalin A (Con. A) renders them suppressive for the response of untreated cells to PHA, Con. A, candidin and allogeneic cells. However, cells stimulated with lipopolysaccharide (LPS) show no suppression."} {"id": "PMID:159935", "title": "Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response.", "content": "The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium.", "contents": "Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response. The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium."} {"id": "PMID:159934", "title": "Manual materials handling: the cause of over-exertion injury and illness in industry.", "content": "It is reported from various sources that overexertion due to lifting, pushing, pulling, and carrying objects accounts for about 27 percent of all compensable industrial injury and illness in the United States. Resulting strain/sprain injuries account for over 50 percent of workmen's compensation clams in many industries. Almont two-thirds of these involve back pain, with reported compensation and medical payments totaling well over one billion dollars annually in the U.S. An estimated 300,000 plus workers will be affected each year, 5 to 10 percent of whom will have a permanent disability and often will be unemployable. This paper attempts to describe four basic approaches used to study this occupational health problem. In so doing, a concerted effort is made to identifiy the gaps in knowledge which need to be more fully researched. The approaches utilized to understand and control the hazards of manual materials handling are: 1) epidemiological studies of job and worker attributes to identify those that individually and in combination cause musculoskeletal incidents, 2) psychophysical studies to ascertain the volitional tolerance of workers to the stress mitigated by manual materials-handling activities, 3) biomechanical studies of the musculoskeletal system during common exertions required in manual materials-handling activities, and 4) physiological studies of the strain imposed on the cardiovascular system during repeated load-handling activities. The state of knowledge from each of these approaches is summarized briefly, and a case is made that much research is still needed to substantiate the necessary controls to lessen the economic burden and human suffering associated with manual materials-handling acts in industry.", "contents": "Manual materials handling: the cause of over-exertion injury and illness in industry. It is reported from various sources that overexertion due to lifting, pushing, pulling, and carrying objects accounts for about 27 percent of all compensable industrial injury and illness in the United States. Resulting strain/sprain injuries account for over 50 percent of workmen's compensation clams in many industries. Almont two-thirds of these involve back pain, with reported compensation and medical payments totaling well over one billion dollars annually in the U.S. An estimated 300,000 plus workers will be affected each year, 5 to 10 percent of whom will have a permanent disability and often will be unemployable. This paper attempts to describe four basic approaches used to study this occupational health problem. In so doing, a concerted effort is made to identifiy the gaps in knowledge which need to be more fully researched. The approaches utilized to understand and control the hazards of manual materials handling are: 1) epidemiological studies of job and worker attributes to identify those that individually and in combination cause musculoskeletal incidents, 2) psychophysical studies to ascertain the volitional tolerance of workers to the stress mitigated by manual materials-handling activities, 3) biomechanical studies of the musculoskeletal system during common exertions required in manual materials-handling activities, and 4) physiological studies of the strain imposed on the cardiovascular system during repeated load-handling activities. The state of knowledge from each of these approaches is summarized briefly, and a case is made that much research is still needed to substantiate the necessary controls to lessen the economic burden and human suffering associated with manual materials-handling acts in industry."} {"id": "PMID:159936", "title": "Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes.", "content": "Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen.", "contents": "Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes. Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen."} {"id": "PMID:159937", "title": "B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse.", "content": "The B6.C-H-2bm12 mutant is described and evidence is presented for the mutational site occurring in the IA subregion. The mutant is of the gain and loss type as bm12 in equilibrium or formed from C57BL/6 grafts are rejected in 14-16 d. Mapping studies by the gene-complementation method using H-2 recombinant strains place the mutation in the K or IA regions of the H-2 complex and furthermore, the use of this test and the use of other H-2 mutants indicate that H-2Kb is not the site of the mutation, making the IA region the most likely site. Serological analysis with a battery of H-2b, Iab, and other Ia sera, both by cytotoxicity, rosetting, and also by absorption analysis, indicated no alteration in H-2 specificities, particularly in H-2.K33. By contrast, all of the Iab specificities coded for by the IA subregion (Ia.3, 8, 9, 15, and possibly 20) are extensively altered and are either absent or greatly reduced in amount indicating an extensive alteration in the Ia-bearing molecule. The bm12 mutant strongly stimulates the parental C57BL/6 strain in an mixed lymphocyte reaction (MLR), and the reciprocal also occurs, the degree of stimulation being similar to that obtained with K + IA differences originating in another H-2 haplotype and points to the mutation effecting the Lad-1 locus. The presence of an extensive histocompatibility change, a marked alteration in the serologically detected Ia specificities, and a strong MLR, all produced by the one mutation, provides strong evidence for the identity of the Ia-1, Lad-1, and H-2(IA) loci in the IA subregion. The bm12 mutant should be of value in determining the relationship of Ia specificities, Ir genes, and other phenomena effected by the I region.", "contents": "B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse. The B6.C-H-2bm12 mutant is described and evidence is presented for the mutational site occurring in the IA subregion. The mutant is of the gain and loss type as bm12 in equilibrium or formed from C57BL/6 grafts are rejected in 14-16 d. Mapping studies by the gene-complementation method using H-2 recombinant strains place the mutation in the K or IA regions of the H-2 complex and furthermore, the use of this test and the use of other H-2 mutants indicate that H-2Kb is not the site of the mutation, making the IA region the most likely site. Serological analysis with a battery of H-2b, Iab, and other Ia sera, both by cytotoxicity, rosetting, and also by absorption analysis, indicated no alteration in H-2 specificities, particularly in H-2.K33. By contrast, all of the Iab specificities coded for by the IA subregion (Ia.3, 8, 9, 15, and possibly 20) are extensively altered and are either absent or greatly reduced in amount indicating an extensive alteration in the Ia-bearing molecule. The bm12 mutant strongly stimulates the parental C57BL/6 strain in an mixed lymphocyte reaction (MLR), and the reciprocal also occurs, the degree of stimulation being similar to that obtained with K + IA differences originating in another H-2 haplotype and points to the mutation effecting the Lad-1 locus. The presence of an extensive histocompatibility change, a marked alteration in the serologically detected Ia specificities, and a strong MLR, all produced by the one mutation, provides strong evidence for the identity of the Ia-1, Lad-1, and H-2(IA) loci in the IA subregion. The bm12 mutant should be of value in determining the relationship of Ia specificities, Ir genes, and other phenomena effected by the I region."} {"id": "PMID:159938", "title": "Ontogeny of culture-generated suppressor cells.", "content": "Culture of murine lymphoid cells without added antigen results in the generation of cells which suppress a variety of in vitro immune responses, such as the mixed lymphocyte response (MLR) and the generation of alloreactive cytotoxic T cells (CTL). The ontogeny of this phenomenon was studied. Cells which suppressed the MLR after preculture were isolated from spleens and hematopoietic livers of fetal and young (less than 1 wk old) mice. On the other hand, the generation of alloreactive CTL could be suppressed only by precultured spleen cells taken from 1-w-old or older mice. The parallel between the development of the suppressor functions and the maturation of the responses they regulate, suggests a possible biological significance of the effect.", "contents": "Ontogeny of culture-generated suppressor cells. Culture of murine lymphoid cells without added antigen results in the generation of cells which suppress a variety of in vitro immune responses, such as the mixed lymphocyte response (MLR) and the generation of alloreactive cytotoxic T cells (CTL). The ontogeny of this phenomenon was studied. Cells which suppressed the MLR after preculture were isolated from spleens and hematopoietic livers of fetal and young (less than 1 wk old) mice. On the other hand, the generation of alloreactive CTL could be suppressed only by precultured spleen cells taken from 1-w-old or older mice. The parallel between the development of the suppressor functions and the maturation of the responses they regulate, suggests a possible biological significance of the effect."} {"id": "PMID:159939", "title": "The receptor specificity of alloreactive T cells. Distinction between stimulator K, I, and D region products and degeneracy of third-party H-2 recognition by low-affinity T cells.", "content": "The specificity of binding of stimulator-derived H-2 antigens by mixed lymphocyte culture (MLC)-activated T blasts was investigated under conditions of antigen excess. We have shown that the detectable proportion of alloantigen-binding blasts from primary MLC is a function of antigen concentration, and can represent up to more than 90 percent of total blasts, when the antigen is presented in the appropriate form (on mitomycin-treated viable stimulator cells, or membrane vesicles prepared from lipopolysaccharide blasts), and at nonlimiting concentration. Thus stimulator alloantigen-binding directly parallels the proliferative response and is not restricted to a subpopulation of T blasts. However, the marked dependence of the binding on antigen concentration indicates that cells with a wide range of receptor affinities for the stimulating determinants are involved. In view of this possibility, the specificity of binding by these cells was studied. We have demonstrated that stimulator K, I, and D region products are bound by nonoverlapping subpopulations of blasts, the sum of which may represent 93 percent of total blasts. Thus, specific distinction by these cells between different H-2 region products is not affected by the putative heterogeneity in terms of receptor affinities. However, specificity with respect to unrelated H-2 haplotypes is strictly dependent on antigen concentration. A preferential binding of stimulator membrane vesicles occurs at limiting concentrations; whereas the majority of blasts bind stimulator and third- party vesicles equally well at high vesicle concentrations. The binding of both vesicle types is specific in that it can be inhibited with the relevant anti-H-2 sera. Furthermore, stimulator and third-party vesicles seem to compete for binding sites on the same cells, as shown by cold antigen inhibition. From these results, we propose that there is an imperfect distinction between stimulator and third-party H-2 antigens by the majority of primary MLC blasts. In contrast, highly selected long-term MLC blasts do not bind third-party H-2 antigens at any concentration, and seem to have high affinity for the stimulating antigens. We conclude that large numbers of clones with low-affinity (cross- reactive) receptors are generated in primary MLC, most of which become eliminated during long-term selection. This implies that the frequency of cells strictly specific for nonshared stimulating determinants must be minute.", "contents": "The receptor specificity of alloreactive T cells. Distinction between stimulator K, I, and D region products and degeneracy of third-party H-2 recognition by low-affinity T cells. The specificity of binding of stimulator-derived H-2 antigens by mixed lymphocyte culture (MLC)-activated T blasts was investigated under conditions of antigen excess. We have shown that the detectable proportion of alloantigen-binding blasts from primary MLC is a function of antigen concentration, and can represent up to more than 90 percent of total blasts, when the antigen is presented in the appropriate form (on mitomycin-treated viable stimulator cells, or membrane vesicles prepared from lipopolysaccharide blasts), and at nonlimiting concentration. Thus stimulator alloantigen-binding directly parallels the proliferative response and is not restricted to a subpopulation of T blasts. However, the marked dependence of the binding on antigen concentration indicates that cells with a wide range of receptor affinities for the stimulating determinants are involved. In view of this possibility, the specificity of binding by these cells was studied. We have demonstrated that stimulator K, I, and D region products are bound by nonoverlapping subpopulations of blasts, the sum of which may represent 93 percent of total blasts. Thus, specific distinction by these cells between different H-2 region products is not affected by the putative heterogeneity in terms of receptor affinities. However, specificity with respect to unrelated H-2 haplotypes is strictly dependent on antigen concentration. A preferential binding of stimulator membrane vesicles occurs at limiting concentrations; whereas the majority of blasts bind stimulator and third- party vesicles equally well at high vesicle concentrations. The binding of both vesicle types is specific in that it can be inhibited with the relevant anti-H-2 sera. Furthermore, stimulator and third-party vesicles seem to compete for binding sites on the same cells, as shown by cold antigen inhibition. From these results, we propose that there is an imperfect distinction between stimulator and third-party H-2 antigens by the majority of primary MLC blasts. In contrast, highly selected long-term MLC blasts do not bind third-party H-2 antigens at any concentration, and seem to have high affinity for the stimulating antigens. We conclude that large numbers of clones with low-affinity (cross- reactive) receptors are generated in primary MLC, most of which become eliminated during long-term selection. This implies that the frequency of cells strictly specific for nonshared stimulating determinants must be minute."} {"id": "PMID:159940", "title": "T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide.", "content": "As measured by [(3)H]thymidine uptake, spleen cells of mice injected 7 d previously with a single dose of cyclophosphamide (Cy) (125 mg x kg (-1)) gave an enhanced response to dextran sulfate (DS), a diminished response to lipopolysaccharide (LPS), and a normal response to concanavalin A. Addition of syngeneic thymocytes to spleen cells inhibited the enhanced response of the cells to DS and slightly enhanced their response to LPS. Pretreatment of thymocytes by 4-hydroxyperoxycyclophosphamide (4HP-Cy) in vitro (an in vitro active derivative of Cy) abrogated the effect of thymocytes on the DS response but not on the LPS response. Pretreatment of spleen cells by small doses of 4HP-Cy (0.1-1.0 mug. ml(-1)) in vitro enhanced the capacity of the cells to respond to DS but either did not affect, or even diminished their capacity to respond to LPS. The enhancement of the DS response by 4HP-Cy treatment could not be detected using spleen cells depleted of T cells or lacking functioning T cells. 4HP-Cy doses more than 3 mug ml(-1) diminished or abolished the capacity of the spleen cells to respond to LPS as well as their capacity to respond to DS. The results show (a) that in contrast to the LPS-reactive B-lymphocyte subset, the proliferative capacity of DS-reactive subset is negatively controlled by a Cy- and 4HP-Cy-sensitive T-cell subset and (b) that these T- suppressor cells are more sensitive to Cy and 4HP-Cy (to their respective active alkylating metabolites) than B lymphocytes and T cells carrying other immunological functions.", "contents": "T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide. As measured by [(3)H]thymidine uptake, spleen cells of mice injected 7 d previously with a single dose of cyclophosphamide (Cy) (125 mg x kg (-1)) gave an enhanced response to dextran sulfate (DS), a diminished response to lipopolysaccharide (LPS), and a normal response to concanavalin A. Addition of syngeneic thymocytes to spleen cells inhibited the enhanced response of the cells to DS and slightly enhanced their response to LPS. Pretreatment of thymocytes by 4-hydroxyperoxycyclophosphamide (4HP-Cy) in vitro (an in vitro active derivative of Cy) abrogated the effect of thymocytes on the DS response but not on the LPS response. Pretreatment of spleen cells by small doses of 4HP-Cy (0.1-1.0 mug. ml(-1)) in vitro enhanced the capacity of the cells to respond to DS but either did not affect, or even diminished their capacity to respond to LPS. The enhancement of the DS response by 4HP-Cy treatment could not be detected using spleen cells depleted of T cells or lacking functioning T cells. 4HP-Cy doses more than 3 mug ml(-1) diminished or abolished the capacity of the spleen cells to respond to LPS as well as their capacity to respond to DS. The results show (a) that in contrast to the LPS-reactive B-lymphocyte subset, the proliferative capacity of DS-reactive subset is negatively controlled by a Cy- and 4HP-Cy-sensitive T-cell subset and (b) that these T- suppressor cells are more sensitive to Cy and 4HP-Cy (to their respective active alkylating metabolites) than B lymphocytes and T cells carrying other immunological functions."} {"id": "PMID:159941", "title": "DNA-mediated genetic changes in Neurospora crassa.", "content": "Evidence for genetic transformation in Neurospora crassa is based on the observations that allo-DNA has a specific effect in producing transformants which is abolished by DNAase treatment and that iso-DNA is not effective in transformation. Here, unambiguous evidence for genetic transformation is provided by transfer of a temperature-sensitive inositol requirement from a donor to a recipient strain. Data provided also suggest the role of growth conditions and the involvement of a nuclease gene in the DNA uptake and transformation of N. crassa.", "contents": "DNA-mediated genetic changes in Neurospora crassa. Evidence for genetic transformation in Neurospora crassa is based on the observations that allo-DNA has a specific effect in producing transformants which is abolished by DNAase treatment and that iso-DNA is not effective in transformation. Here, unambiguous evidence for genetic transformation is provided by transfer of a temperature-sensitive inositol requirement from a donor to a recipient strain. Data provided also suggest the role of growth conditions and the involvement of a nuclease gene in the DNA uptake and transformation of N. crassa."} {"id": "PMID:159942", "title": "Demonstration of intracellular growth of gonococci in human phagocytes using spectinomycin to kill extracellular organisms.", "content": "The use of spectinomycin to kill extracellular bacterial in phagocytosis tests with gonococci and human polymorphonuclear phagocytes allowed the demonstration of a greater degree of intracellular survival and growth than in previous tests using penicillin.", "contents": "Demonstration of intracellular growth of gonococci in human phagocytes using spectinomycin to kill extracellular organisms. The use of spectinomycin to kill extracellular bacterial in phagocytosis tests with gonococci and human polymorphonuclear phagocytes allowed the demonstration of a greater degree of intracellular survival and growth than in previous tests using penicillin."} {"id": "PMID:159944", "title": "Prognostic factors in omphalocele and gastroschisis.", "content": "Size of the abdominal wall defect, viscera exposed or herniated, birth weight, associated medical conditions and congenital anomalies, mode and complications of treatment, and the use of total parenteral alimentation was reviewed in 79 cases of omphalocele and 44 cases of gastroschisis treated in the past 10 yr. Sixty-seven percent of infants with omphalocele and 73% of those with gastroschisis survived. In omphalocele, the most important factors affecting mortality were the presence of other associated abnormalities and low birth weight. The size of the abdominal wall defect, the viscera herniated, and the mode of treatment did not appear to affect mortality. In gastroschisis, the size of the abdominal defect, birth weight, viscera exposed or herniated, and associated anomalies were not significant factors affecting mortality. Mortality was usually secondary to intestinal or wound complications. Statistical analysis could not prove that primary repair resulted in greater survival than the use of a silon pouch, but analysis of complications clearly indicates that the former method is preferable and that silon pouch should be reserved for cases in which primary repair is not possible.", "contents": "Prognostic factors in omphalocele and gastroschisis. Size of the abdominal wall defect, viscera exposed or herniated, birth weight, associated medical conditions and congenital anomalies, mode and complications of treatment, and the use of total parenteral alimentation was reviewed in 79 cases of omphalocele and 44 cases of gastroschisis treated in the past 10 yr. Sixty-seven percent of infants with omphalocele and 73% of those with gastroschisis survived. In omphalocele, the most important factors affecting mortality were the presence of other associated abnormalities and low birth weight. The size of the abdominal wall defect, the viscera herniated, and the mode of treatment did not appear to affect mortality. In gastroschisis, the size of the abdominal defect, birth weight, viscera exposed or herniated, and associated anomalies were not significant factors affecting mortality. Mortality was usually secondary to intestinal or wound complications. Statistical analysis could not prove that primary repair resulted in greater survival than the use of a silon pouch, but analysis of complications clearly indicates that the former method is preferable and that silon pouch should be reserved for cases in which primary repair is not possible."} {"id": "PMID:159945", "title": "Effects of endurance training on muscle fibre ATP-ase activity, capillary supply and mitochondrial content in man.", "content": "Seven young females were subjected to 24 weeks of intensive endurance training. Adaptive changes in myofibrillary ATP-ase activity, capillary supply and mitochondrial content were investigated with light- and electron microscopy in needle biopsies from the quadriceps femoris. 1. The average value for the maximal oxygen uptake increased from 45.7 to 57.2 (ml . kg-1 min-1) (25.2%, P less than 0.005). 2. The average number of capillaries per muscle fibre increased from 1.39 to 1.79 (28.8%, P less than 0.005). Since no significant change in fibre area was found, this suggests that a considerable number of new capillaries have been formed during the training period. 3. An increased capillary supply of all fibre types was found, being greatest for type I and smallest for type IIB. 4. The relative amount of type I fibres before and after the training period was 57.9 and 56.5% respectively (n.s.), for type IIA fibres 26.4 and 31.5% (P less than 0.005), for type IIB fibres 9.2 and 3.4% (P less than 0.005) and for type IIC fibres 0.4 and 2.2% (P less than 0.005). Thus, in the type II group, significant changes in subtypes take place during the endurance training. The data suggest that type IIAB may represent a transitional state between type IIA and IIB. 5. Correlation of capillary supply, myofibrillar ATP-ase activity and mitochondrial content (determined semiquantitatively of individual muscle fibres indicators that the capillary supply to a given fibre is more closely related to its mitochondrial content than to the fibre type as determined on the basis of myofibrillar ATP-ase activity.", "contents": "Effects of endurance training on muscle fibre ATP-ase activity, capillary supply and mitochondrial content in man. Seven young females were subjected to 24 weeks of intensive endurance training. Adaptive changes in myofibrillary ATP-ase activity, capillary supply and mitochondrial content were investigated with light- and electron microscopy in needle biopsies from the quadriceps femoris. 1. The average value for the maximal oxygen uptake increased from 45.7 to 57.2 (ml . kg-1 min-1) (25.2%, P less than 0.005). 2. The average number of capillaries per muscle fibre increased from 1.39 to 1.79 (28.8%, P less than 0.005). Since no significant change in fibre area was found, this suggests that a considerable number of new capillaries have been formed during the training period. 3. An increased capillary supply of all fibre types was found, being greatest for type I and smallest for type IIB. 4. The relative amount of type I fibres before and after the training period was 57.9 and 56.5% respectively (n.s.), for type IIA fibres 26.4 and 31.5% (P less than 0.005), for type IIB fibres 9.2 and 3.4% (P less than 0.005) and for type IIC fibres 0.4 and 2.2% (P less than 0.005). Thus, in the type II group, significant changes in subtypes take place during the endurance training. The data suggest that type IIAB may represent a transitional state between type IIA and IIB. 5. Correlation of capillary supply, myofibrillar ATP-ase activity and mitochondrial content (determined semiquantitatively of individual muscle fibres indicators that the capillary supply to a given fibre is more closely related to its mitochondrial content than to the fibre type as determined on the basis of myofibrillar ATP-ase activity."} {"id": "PMID:159946", "title": "The responses of primary spindle afferents to fusimotor stimulation at constant and abruptly changing rates.", "content": "1. Single fusimotor fibres to de-efferented soleus of the cat were stimulated to investigate the size and time course of the responses elicited in single primary spindle afferents. The muscle was kept at constant length close to the physiological maximum. Constant and alternating rates of fusimotor stimulation were used: (a) repetitive stimulation at constant rate (maintained stimulation); (b) modulated stimulation with the rate of activation alternating between two constant levels at repeat frequencies between 0.09 and 2 Hz (rectangular stimulation). The responses were averaged and displayed as post-stimulus time (pst) histograms (a) or as cycle histograms (b). 2. During static fusimotor stimulation the pst histograms could be clearly modulated over a range of rates of stimulation. However, histogram modulation was not a prerequisite of static action since with different fibres the degree of modulation could range from deeply modulated to completely non-modulated to completely non-modulated. 3. Dynamic fusimotor stimulation was almost always accompanied by non-modulated pst histograms. 4. Primary spindle afferents responded to rectangular stimulation of either kind of fusimotor fibre with an approximately rectangular modulation of the rate of discharge. At the repeat frequencies studied the size of the responses was appreciably larger with static than with dynamic activation. It was assessed as 'fusimotor rate-sensitivity during alternating stimulation' by the response/stimulus ratio which is defined as change in firing/change in alternating rate of stimulation, in impulses/stimuli. The mean values of rate-sensitivity were 1.35 impulses/stimuli (statics) and 0.29 (dynamics), with a static/dynamic ratio of 4.7. 5. The afferents' 'fusimotor rate-sensitivity during steady stimulation' (change in firing/change in maintained rate of stimulation( was also determined. The mean values were 0.78 (static) and 0.37 (dynamics), with a static/dynamic ratio of 2.1. 6. The time course of the responses to rectangular stimulation was of the same order of magnitude for static and dynamic fibres. It was assessed by fitting a single exponential to the rising and falling phase of cycle histograms. The mean values of the time constants for static fibres were 58 msec (rising phase) and 59 msec (falling phase), and for dynamic fibres 34 msec (rising phase) and 49 msec (falling phase). The differences were statistically non-significant. 7. The significance of the modulation in pst histograms and the mechanisms and functional implications of the differences in rate-sensitivity are discussed. It is concluded that at constant muscle length static and dynamic fusimotor fibres differ significantly by the size rather than the speed of their action on primary spindle afferents.", "contents": "The responses of primary spindle afferents to fusimotor stimulation at constant and abruptly changing rates. 1. Single fusimotor fibres to de-efferented soleus of the cat were stimulated to investigate the size and time course of the responses elicited in single primary spindle afferents. The muscle was kept at constant length close to the physiological maximum. Constant and alternating rates of fusimotor stimulation were used: (a) repetitive stimulation at constant rate (maintained stimulation); (b) modulated stimulation with the rate of activation alternating between two constant levels at repeat frequencies between 0.09 and 2 Hz (rectangular stimulation). The responses were averaged and displayed as post-stimulus time (pst) histograms (a) or as cycle histograms (b). 2. During static fusimotor stimulation the pst histograms could be clearly modulated over a range of rates of stimulation. However, histogram modulation was not a prerequisite of static action since with different fibres the degree of modulation could range from deeply modulated to completely non-modulated to completely non-modulated. 3. Dynamic fusimotor stimulation was almost always accompanied by non-modulated pst histograms. 4. Primary spindle afferents responded to rectangular stimulation of either kind of fusimotor fibre with an approximately rectangular modulation of the rate of discharge. At the repeat frequencies studied the size of the responses was appreciably larger with static than with dynamic activation. It was assessed as 'fusimotor rate-sensitivity during alternating stimulation' by the response/stimulus ratio which is defined as change in firing/change in alternating rate of stimulation, in impulses/stimuli. The mean values of rate-sensitivity were 1.35 impulses/stimuli (statics) and 0.29 (dynamics), with a static/dynamic ratio of 4.7. 5. The afferents' 'fusimotor rate-sensitivity during steady stimulation' (change in firing/change in maintained rate of stimulation( was also determined. The mean values were 0.78 (static) and 0.37 (dynamics), with a static/dynamic ratio of 2.1. 6. The time course of the responses to rectangular stimulation was of the same order of magnitude for static and dynamic fibres. It was assessed by fitting a single exponential to the rising and falling phase of cycle histograms. The mean values of the time constants for static fibres were 58 msec (rising phase) and 59 msec (falling phase), and for dynamic fibres 34 msec (rising phase) and 49 msec (falling phase). The differences were statistically non-significant. 7. The significance of the modulation in pst histograms and the mechanisms and functional implications of the differences in rate-sensitivity are discussed. It is concluded that at constant muscle length static and dynamic fusimotor fibres differ significantly by the size rather than the speed of their action on primary spindle afferents."} {"id": "PMID:159947", "title": "On the regional histology and histochemistry of the epididymis of the camel (Camelus dromedarius).", "content": "Distinct morphological regions, initial, middle and terminal segments, were distinguishable histologically; the middle segment was further subdivided into proximal, intermediated and distal parts. PAS-positive, diastase-resistant reaction was detected in the blood vessels, subepithelial tissue and stereocilia of all segments. Acid phosphatase was demonstrated in the epithelial cells with the highest activity being in the proximal part of the middle segment. Non-specific esterase gave a similar reaction but the strongest activity was in the terminal segment. Alkaline phosphatase, adenosine triphosphatase and adenosine monophosphatase were of similar activity in the subepithelial tissue, blood vessels, stereocilia and luminal contents; the strongest reaction occurred in the middle segment. Lactate, succinate, glutamate and glucose-6-phosphate dehydrogenases were examined; LDH was more active than the others particularly in the terminal segment. Some reaction was found in the epithelial cells, subepithelial tissue and luminal contents.", "contents": "On the regional histology and histochemistry of the epididymis of the camel (Camelus dromedarius). Distinct morphological regions, initial, middle and terminal segments, were distinguishable histologically; the middle segment was further subdivided into proximal, intermediated and distal parts. PAS-positive, diastase-resistant reaction was detected in the blood vessels, subepithelial tissue and stereocilia of all segments. Acid phosphatase was demonstrated in the epithelial cells with the highest activity being in the proximal part of the middle segment. Non-specific esterase gave a similar reaction but the strongest activity was in the terminal segment. Alkaline phosphatase, adenosine triphosphatase and adenosine monophosphatase were of similar activity in the subepithelial tissue, blood vessels, stereocilia and luminal contents; the strongest reaction occurred in the middle segment. Lactate, succinate, glutamate and glucose-6-phosphate dehydrogenases were examined; LDH was more active than the others particularly in the terminal segment. Some reaction was found in the epithelial cells, subepithelial tissue and luminal contents."} {"id": "PMID:159948", "title": "The ultrasonic demonstration of fetal abnormalities in utero.", "content": "The demonstration of fetal diseases and anomalies in utero can now be performed with a high degree of accuracy with modern ultrasonic equipment. This paper describes the more common and important fetal anomalies which can be demonstrated by ultrasound and indicates the importance of meticulous attention to technique and the significance of the acquistion of skill in real-time sonography by the physician-sonologist. The thoroughness of all obstetric sonographic examinations is emphasized to enable detection of unsuspected fetal anomalies. Specific methods to demonstrate these anomalies in the high-risk patient are also described. Several pitfalls in the diagnosis of fetal disease in utero are included which show the nonspecificity of some of the ultrasonic signs.", "contents": "The ultrasonic demonstration of fetal abnormalities in utero. The demonstration of fetal diseases and anomalies in utero can now be performed with a high degree of accuracy with modern ultrasonic equipment. This paper describes the more common and important fetal anomalies which can be demonstrated by ultrasound and indicates the importance of meticulous attention to technique and the significance of the acquistion of skill in real-time sonography by the physician-sonologist. The thoroughness of all obstetric sonographic examinations is emphasized to enable detection of unsuspected fetal anomalies. Specific methods to demonstrate these anomalies in the high-risk patient are also described. Several pitfalls in the diagnosis of fetal disease in utero are included which show the nonspecificity of some of the ultrasonic signs."} {"id": "PMID:159951", "title": "Years of life lost through Down's syndrome.", "content": "A congenital genetic condition does not act either as a cause of death or at the time of death only. Hence, years of life lost through such a conditon cannot be calculated in the same way as for a conventional cause of death. The main difference is that a cause of death acting at age x cuts off as many years of life as the dead person might otherwise have expected to live (life expectancy at age x), whereas a congenital genetic condition exposes an affected person to a different schedule of life-threatening risks from birth onwards. In the latter case, years of life lost is calculated as the difference in life expectancy at birth for affected and non-affected persons. This reasoning is worked out in algebraic form and then applied to Down's syndrome. The data base is provided by two large and recent studies, one in Massachusetts and the other in Denmark, of mortality rates among all cases of Down's syndrome, whether in an institution or not, born during a given period of years or living at a given point in time in a fixed geographical area. So calculated, years of life lost through Down's syndrome relative to the United States general population in 1970 was 53.6 years per 1000 livebirths. Prenatal mortality is also discussed.", "contents": "Years of life lost through Down's syndrome. A congenital genetic condition does not act either as a cause of death or at the time of death only. Hence, years of life lost through such a conditon cannot be calculated in the same way as for a conventional cause of death. The main difference is that a cause of death acting at age x cuts off as many years of life as the dead person might otherwise have expected to live (life expectancy at age x), whereas a congenital genetic condition exposes an affected person to a different schedule of life-threatening risks from birth onwards. In the latter case, years of life lost is calculated as the difference in life expectancy at birth for affected and non-affected persons. This reasoning is worked out in algebraic form and then applied to Down's syndrome. The data base is provided by two large and recent studies, one in Massachusetts and the other in Denmark, of mortality rates among all cases of Down's syndrome, whether in an institution or not, born during a given period of years or living at a given point in time in a fixed geographical area. So calculated, years of life lost through Down's syndrome relative to the United States general population in 1970 was 53.6 years per 1000 livebirths. Prenatal mortality is also discussed."} {"id": "PMID:159953", "title": "Children with supernumerary X-chromosome. A ten-year follow-up study of schoolchildren in special classes.", "content": "Pupils from special school classes affected by supernumerary X-chromosomes (eight girls and eighteen boys) were subjected to a follow-up study over a period of ten years. The risks of social behaviour disturbances, criminality and alcohol abuse were studied, together with that of mental disorder. In the case of the girls no statistically significant differences were found. For the boys, the only difference of statistical significance was that the Klinefelter boys showed a lower frequency of social behaviour disturbances that their controls.", "contents": "Children with supernumerary X-chromosome. A ten-year follow-up study of schoolchildren in special classes. Pupils from special school classes affected by supernumerary X-chromosomes (eight girls and eighteen boys) were subjected to a follow-up study over a period of ten years. The risks of social behaviour disturbances, criminality and alcohol abuse were studied, together with that of mental disorder. In the case of the girls no statistically significant differences were found. For the boys, the only difference of statistical significance was that the Klinefelter boys showed a lower frequency of social behaviour disturbances that their controls."} {"id": "PMID:159954", "title": "Erythrocyte copper levels in children with trisomy 21.", "content": "Erythrocyte superoxide dismutase is a cuproprotein displaying increased activity in cases of trisomy 21. In this study, the three erythrocyte copper fractions were compared at constant serum copper levels in children with and without trisomy 21. The labile erythrocyte copper level was found to be identical in both groups of children. Total erythrocyte copper, especially the stable fraction, was increased in cases of trisomy 21. The approximately fifty per cent ob served increase correlates with the augmented superoxide dismutase activity related to the presence of an extra chromosome 21. Measurement of the stable erythrocyte copper fraction could constitute an indirect method for evaluating superoxide dismutase activity.", "contents": "Erythrocyte copper levels in children with trisomy 21. Erythrocyte superoxide dismutase is a cuproprotein displaying increased activity in cases of trisomy 21. In this study, the three erythrocyte copper fractions were compared at constant serum copper levels in children with and without trisomy 21. The labile erythrocyte copper level was found to be identical in both groups of children. Total erythrocyte copper, especially the stable fraction, was increased in cases of trisomy 21. The approximately fifty per cent ob served increase correlates with the augmented superoxide dismutase activity related to the presence of an extra chromosome 21. Measurement of the stable erythrocyte copper fraction could constitute an indirect method for evaluating superoxide dismutase activity."} {"id": "PMID:159960", "title": "An economic evaluation of present and proposed methods of compensating hearing loss.", "content": "The basis for compensation of industrial hearing loss in the Province of Ontario is described, and contrasted with schemes utilized in other parts of Canada, United Kingdom, Australia, and the United States. Changes are suggested for the method used to derive the percentage of permanent disability related to hearing loss. A randomly selected population of claimants for industrial hearing loss have been used to model the economic effect of such changes, which are discussed.", "contents": "An economic evaluation of present and proposed methods of compensating hearing loss. The basis for compensation of industrial hearing loss in the Province of Ontario is described, and contrasted with schemes utilized in other parts of Canada, United Kingdom, Australia, and the United States. Changes are suggested for the method used to derive the percentage of permanent disability related to hearing loss. A randomly selected population of claimants for industrial hearing loss have been used to model the economic effect of such changes, which are discussed."} {"id": "PMID:159962", "title": "In vivo methylation of bacteriophage phi X174 DNA.", "content": "A mutant (designated mec(-)) has been isolated from Escherichia coli C which has lost DNA-cytosine methylase activity and the ability to protect phage lambda against in vivo restriction by the RII endonuclease. This situation is analogous to that observed with an E. coli K-12 mec(-) mutant; thus, the E. coli C methylase appears to have overlapping sequence specificity with the K-12 and RII enzymes; (the latter methylases have been shown previously to recognize the same sequence). Covalently closed, supertwisted double-standed DNA (RFI) was isolated from C mec(+) and C mec(-) cells infected with bacteriophage phiX174. phiX. mec(-) RFI is sensitive to in vitro cleavage by R.EcoRII and is cut twice to produce two fragments of almost equal size. In contrast, phiX.mec(+) RFI is relatively resistant to in vitro cleavage by R.EcoRII. R.BstI, which cleaves mec(+)/RII sites independent of the presence or absence of 5-methylcytosine, cleaves both forms of the RFI and produces two fragments similar in size to those observed with R. EcoRII. These results demonstrate that phiX.mec(+) RFI is methylated in vivo by the host mec(+) enzyme and that this methylation protects the DNA against cleavage by R.EcoRII. This is consistent with the known location of two mec(+)/ RII sequences (viz., [Formula: see text]) on the phiX174 map. Mature singlestranded virion DNA was isolated from phiX174 propagated in C mec(+) or C mec(-) in the presence of l-[methyl-(3)H]methionine. Paper chromatographic analyses of acid hydrolysates revealed that phiX.mec(+) DNA had a 10-fold-higher ratio of [(3)H]5-methylcytosine to [(3)H]cytosine compared to phiX.mec(-). Since phiX.mec(+) contains, on the average, approximately 1 5-methylcytosine residue per viral DNA, we conclude that methylation of phiX174 is mediated by the host mec(+) enzyme only. These results are not consistent with the conclusions of previous reports that phiX174 methylation is mediated by a phage-induced enzyme and that methylation is essential for normal phage development.", "contents": "In vivo methylation of bacteriophage phi X174 DNA. A mutant (designated mec(-)) has been isolated from Escherichia coli C which has lost DNA-cytosine methylase activity and the ability to protect phage lambda against in vivo restriction by the RII endonuclease. This situation is analogous to that observed with an E. coli K-12 mec(-) mutant; thus, the E. coli C methylase appears to have overlapping sequence specificity with the K-12 and RII enzymes; (the latter methylases have been shown previously to recognize the same sequence). Covalently closed, supertwisted double-standed DNA (RFI) was isolated from C mec(+) and C mec(-) cells infected with bacteriophage phiX174. phiX. mec(-) RFI is sensitive to in vitro cleavage by R.EcoRII and is cut twice to produce two fragments of almost equal size. In contrast, phiX.mec(+) RFI is relatively resistant to in vitro cleavage by R.EcoRII. R.BstI, which cleaves mec(+)/RII sites independent of the presence or absence of 5-methylcytosine, cleaves both forms of the RFI and produces two fragments similar in size to those observed with R. EcoRII. These results demonstrate that phiX.mec(+) RFI is methylated in vivo by the host mec(+) enzyme and that this methylation protects the DNA against cleavage by R.EcoRII. This is consistent with the known location of two mec(+)/ RII sequences (viz., [Formula: see text]) on the phiX174 map. Mature singlestranded virion DNA was isolated from phiX174 propagated in C mec(+) or C mec(-) in the presence of l-[methyl-(3)H]methionine. Paper chromatographic analyses of acid hydrolysates revealed that phiX.mec(+) DNA had a 10-fold-higher ratio of [(3)H]5-methylcytosine to [(3)H]cytosine compared to phiX.mec(-). Since phiX.mec(+) contains, on the average, approximately 1 5-methylcytosine residue per viral DNA, we conclude that methylation of phiX174 is mediated by the host mec(+) enzyme only. These results are not consistent with the conclusions of previous reports that phiX174 methylation is mediated by a phage-induced enzyme and that methylation is essential for normal phage development."} {"id": "PMID:159969", "title": "[Classification of acquired aortic stenosis (based on electrocardiographic study data)].", "content": "The article is based on the case records of 192 patients with acquired aortic stenosis and interpretation of the ECG of 187 patients. In this group, 143 patients underwent operation and 8 died in the period of their examination. The purpose of the examination consisted in determining whether or not the ECG could characterize the stage of the cardiac disease. Four types of electrocardiographic changes of the ventricular complex characteristic of left-ventricular hypertrophy were distinguished. On comparing clinical and electrocardiographic findings, no clear dependence was revealed between the clinical manifestations of the stenosis and the severity of the hypertrophic process in the muscle of the left ventricle according to the ECG data. The information gained by means of ECG is confirmed by the results of pathomorphological examination. The authors suggest a clinical classification of acquired aortic stenosis based on the function changes in the left-ventricular myocardium as determined from the ECG.", "contents": "[Classification of acquired aortic stenosis (based on electrocardiographic study data)]. The article is based on the case records of 192 patients with acquired aortic stenosis and interpretation of the ECG of 187 patients. In this group, 143 patients underwent operation and 8 died in the period of their examination. The purpose of the examination consisted in determining whether or not the ECG could characterize the stage of the cardiac disease. Four types of electrocardiographic changes of the ventricular complex characteristic of left-ventricular hypertrophy were distinguished. On comparing clinical and electrocardiographic findings, no clear dependence was revealed between the clinical manifestations of the stenosis and the severity of the hypertrophic process in the muscle of the left ventricle according to the ECG data. The information gained by means of ECG is confirmed by the results of pathomorphological examination. The authors suggest a clinical classification of acquired aortic stenosis based on the function changes in the left-ventricular myocardium as determined from the ECG."} {"id": "PMID:159970", "title": "[Characteristics of the effect and the effectiveness of the terrain cure in patients 6-12 months after a myocardial infarct].", "content": "The effect of terrain cure, the dose of which was determined by the level of physical tolerance, was studied in 121 patients treated according to a rehabilitation program on the South coast of the Crimea 6 to 12 months after myocardial infarction. According to the peculiarities of the clinical electrocardiographic and hemodynamic reactions recorded by examination during terrain cure, groups of patients differing in the degree of adaptation to the load of the cure were distinguished. This made it possible to differentiate the treatment and appraise its results objectively. The clinical efficacy was more marked in patients with relatively complete adaptation to the load experienced during terrain cure. The terrain cure lods, the doses of which are determined by the level of physical tolerance and increased step by step with due account for the peculiarities of the patients' reactions, are an effective physical and psycho-emotional factor in the complex of measures applied for rehabilitation after myocardial infarction.", "contents": "[Characteristics of the effect and the effectiveness of the terrain cure in patients 6-12 months after a myocardial infarct]. The effect of terrain cure, the dose of which was determined by the level of physical tolerance, was studied in 121 patients treated according to a rehabilitation program on the South coast of the Crimea 6 to 12 months after myocardial infarction. According to the peculiarities of the clinical electrocardiographic and hemodynamic reactions recorded by examination during terrain cure, groups of patients differing in the degree of adaptation to the load of the cure were distinguished. This made it possible to differentiate the treatment and appraise its results objectively. The clinical efficacy was more marked in patients with relatively complete adaptation to the load experienced during terrain cure. The terrain cure lods, the doses of which are determined by the level of physical tolerance and increased step by step with due account for the peculiarities of the patients' reactions, are an effective physical and psycho-emotional factor in the complex of measures applied for rehabilitation after myocardial infarction."} {"id": "PMID:159972", "title": "[Diastolic relaxation disturbance and the compensatory role of the left atrium in hypertension].", "content": "The processes of contraction and relaxation of the myocardium, the compensatory role of the left auricle were studied by echocardiography in patients suffering from essential hypertension with varied intensity of myocardial hypertrophy of the left ventricle. 44 patients with essential hypertension and 10 healthy individuals were examined. The patients suffering from essential hypertension not attended by myocardial hypertrophy of the left ventricle show an increase in inotropism and in the extent of diastolic relaxation as compared to controls. A significant rise of the myocardial weight of the left ventricle entails a reduction in myocardial contractility and in the extent of diastolic relaxation. As hypertrophy of the left ventricle increases, the compensatory role of the left auricle rises, thus ensuring increased diastolic filling and maintenance of the left ventricular contractility.", "contents": "[Diastolic relaxation disturbance and the compensatory role of the left atrium in hypertension]. The processes of contraction and relaxation of the myocardium, the compensatory role of the left auricle were studied by echocardiography in patients suffering from essential hypertension with varied intensity of myocardial hypertrophy of the left ventricle. 44 patients with essential hypertension and 10 healthy individuals were examined. The patients suffering from essential hypertension not attended by myocardial hypertrophy of the left ventricle show an increase in inotropism and in the extent of diastolic relaxation as compared to controls. A significant rise of the myocardial weight of the left ventricle entails a reduction in myocardial contractility and in the extent of diastolic relaxation. As hypertrophy of the left ventricle increases, the compensatory role of the left auricle rises, thus ensuring increased diastolic filling and maintenance of the left ventricular contractility."} {"id": "PMID:159973", "title": "[Hemodynamic characteristics of spontaneous (hereditarily determined) hypertension in rats. 1].", "content": "The hemodynamics and contractility function of the myocardium were studied in rats of 2 age groups with normal or increased arterial pressure under conditions of an acute experiment with the use of electromagnetic flowmetry. In the early hypertensive stage, the rise in arterial pressure is mainly caused by an increase in the cardiac output due to intensified work of the heart in normal peripheral resistance to the blood flow. With the gradual stabilization of the hypertension it is observed, on the whole, that the hyperkinetic type of circulation encountered in the early stage changes to eu- and hypokinetic types in the stage of stable hypertension when the high arterial pressure is maintained by the increased peripheral resistance to the blood flow while the contractility function of the myocardium is diminished.", "contents": "[Hemodynamic characteristics of spontaneous (hereditarily determined) hypertension in rats. 1]. The hemodynamics and contractility function of the myocardium were studied in rats of 2 age groups with normal or increased arterial pressure under conditions of an acute experiment with the use of electromagnetic flowmetry. In the early hypertensive stage, the rise in arterial pressure is mainly caused by an increase in the cardiac output due to intensified work of the heart in normal peripheral resistance to the blood flow. With the gradual stabilization of the hypertension it is observed, on the whole, that the hyperkinetic type of circulation encountered in the early stage changes to eu- and hypokinetic types in the stage of stable hypertension when the high arterial pressure is maintained by the increased peripheral resistance to the blood flow while the contractility function of the myocardium is diminished."} {"id": "PMID:159974", "title": "[X-ray angiocardiographic characteristics of the heart in arterial hypertension].", "content": "Correlation-statistical analysis of the roentgenocardiometric indices and the findings of left ventriculography in 30 patients with arterial hypertension was conducted. A significant inter-relationship of the roentgenometrical criteria of enlargement of the heart (cardiothoracic index, the extent of convexity of the arch of the pulmonary artery and, to a lesser measure, the cardiac volume) with the mass of the myocardium and the thickness of the left ventricular wall was revealed. The roentgenological criteria may complement the existing methods of the assessment of the degree of myocardial hypertrophy in arterial hypertension.", "contents": "[X-ray angiocardiographic characteristics of the heart in arterial hypertension]. Correlation-statistical analysis of the roentgenocardiometric indices and the findings of left ventriculography in 30 patients with arterial hypertension was conducted. A significant inter-relationship of the roentgenometrical criteria of enlargement of the heart (cardiothoracic index, the extent of convexity of the arch of the pulmonary artery and, to a lesser measure, the cardiac volume) with the mass of the myocardium and the thickness of the left ventricular wall was revealed. The roentgenological criteria may complement the existing methods of the assessment of the degree of myocardial hypertrophy in arterial hypertension."} {"id": "PMID:159975", "title": "Reticuloendothelial and mesangial function in murine immune complex glomerulonephritis.", "content": "The function of the mesangial and reticuloendothelial system was evaluated in normal mice and in mice with nephritis induced by lymphocytic choriomeningitis (LCM) virus infection. Heat-aggregated human immunoglobulin (AlgG) and colloidal carbon served as traceable materials which could be detected in animals' blood and tissues. LCM virus-infected proteinuric (LCM-P) mice, as compared to normal mice or LCM-infected nonproteinuric (LCM) mice, had greater accumulation of AIgG in their glomeruli at all times of examination following i.p. injection of AIgG. The removal rate of AIgG from the kidney, however, was the same in normal and LCM-P mice, indicating an unimpaired mesangial clearing system. This suggested that other mechanisms were responsible for the increased glomerular accumulation of AIgG in LCM-P mice. Reticuloendothelial function was examined directly by i.v. injection of AIgG or colloidal carbon. The data demonstrate that in this model of immune complex glomerulonephritis, colloidal material tested was removed from the blood at a slower rate than it was in normal mice. Deficient clearance of endogenous blood-borne immune complex-like material may be one of the factors playing a role in the accumulation of immune complex-like material in the glomeruli of these nephritic animals.", "contents": "Reticuloendothelial and mesangial function in murine immune complex glomerulonephritis. The function of the mesangial and reticuloendothelial system was evaluated in normal mice and in mice with nephritis induced by lymphocytic choriomeningitis (LCM) virus infection. Heat-aggregated human immunoglobulin (AlgG) and colloidal carbon served as traceable materials which could be detected in animals' blood and tissues. LCM virus-infected proteinuric (LCM-P) mice, as compared to normal mice or LCM-infected nonproteinuric (LCM) mice, had greater accumulation of AIgG in their glomeruli at all times of examination following i.p. injection of AIgG. The removal rate of AIgG from the kidney, however, was the same in normal and LCM-P mice, indicating an unimpaired mesangial clearing system. This suggested that other mechanisms were responsible for the increased glomerular accumulation of AIgG in LCM-P mice. Reticuloendothelial function was examined directly by i.v. injection of AIgG or colloidal carbon. The data demonstrate that in this model of immune complex glomerulonephritis, colloidal material tested was removed from the blood at a slower rate than it was in normal mice. Deficient clearance of endogenous blood-borne immune complex-like material may be one of the factors playing a role in the accumulation of immune complex-like material in the glomeruli of these nephritic animals."} {"id": "PMID:159978", "title": "Effect of prostaglandin E on immune complex nephritis in NZB/W mice.", "content": "Pharmacologic quantities of prostaglandin alter the immune complex nephritis of NZB/W mice. To study the mechanism of this change, NZB/W mice received 200 micrograms. of prostaglandin E1 or E2 twice daily starting at 2, 4, or 6 months of age. Mice were sacrificed at bimonthy intervals, renal function and serologic parameters were evaluated, and renal tissue was examined by light, fluorescence, and electron microscopy. Therapy decreased the incidence of proteinuria, lessened renal pathology, and prolonged survival. Maximal beneficial effects occurred when treatment began at 2 months of age. The most striking change was a decrease in the rate of immune complexes depositing in the mesangium and their absence from peripheral loops. Accompanying this change was a reduction in glomerular hypercellularity and a decrease in renal perivascular and interstitial mononuclear infiltrates. By contrast, treatment did not alter serum levels of immunoglobulins, antinuclear antibodies, and antisingle or double-stranded DNA. These results indicate that prostaglandin E is capable of prolonging survival in NZB/W mice by decreasing the rate of immune complexes depositing in glomeruli.", "contents": "Effect of prostaglandin E on immune complex nephritis in NZB/W mice. Pharmacologic quantities of prostaglandin alter the immune complex nephritis of NZB/W mice. To study the mechanism of this change, NZB/W mice received 200 micrograms. of prostaglandin E1 or E2 twice daily starting at 2, 4, or 6 months of age. Mice were sacrificed at bimonthy intervals, renal function and serologic parameters were evaluated, and renal tissue was examined by light, fluorescence, and electron microscopy. Therapy decreased the incidence of proteinuria, lessened renal pathology, and prolonged survival. Maximal beneficial effects occurred when treatment began at 2 months of age. The most striking change was a decrease in the rate of immune complexes depositing in the mesangium and their absence from peripheral loops. Accompanying this change was a reduction in glomerular hypercellularity and a decrease in renal perivascular and interstitial mononuclear infiltrates. By contrast, treatment did not alter serum levels of immunoglobulins, antinuclear antibodies, and antisingle or double-stranded DNA. These results indicate that prostaglandin E is capable of prolonging survival in NZB/W mice by decreasing the rate of immune complexes depositing in glomeruli."} {"id": "PMID:159979", "title": "A study of causes of unemployment among agricultural labourers afflicted by leprosy.", "content": "116 patients consisting of 54 males and 62 females, all engaged in agriculture were interviewed to find out the cause of their unemployment. Deformity seemed to be the major factor responsible for the loss of job among them, which was prevalent among advanced age group (Males--50, Females--53.5). Since the measures to rehabilitate them are rather difficult, it is essential to educate them on the methods of prevention of deformities and their importance. If not, they invariably loose their job at an age when they cannot train themselves for a suitable alternative job to earn their livelihood.", "contents": "A study of causes of unemployment among agricultural labourers afflicted by leprosy. 116 patients consisting of 54 males and 62 females, all engaged in agriculture were interviewed to find out the cause of their unemployment. Deformity seemed to be the major factor responsible for the loss of job among them, which was prevalent among advanced age group (Males--50, Females--53.5). Since the measures to rehabilitate them are rather difficult, it is essential to educate them on the methods of prevention of deformities and their importance. If not, they invariably loose their job at an age when they cannot train themselves for a suitable alternative job to earn their livelihood."} {"id": "PMID:159982", "title": "Phosphorprotein intermediate in the Ca2+-dependent ATPase reaction of macrophage plasma membrane.", "content": "ATPase activity and phosphorylation by [gamma-32P] ATP of isolated plasma membrane of alveolar macorphages are stimulated in a parallel fashion by physiologic concentrations of Ca2+, with half-maximal activating effect of this ion at (3--7) X 10(-7) M. For various membrane preparations, a direct proportionality exists between Ca2+-dependent ATPase activity and amount of 32P incorporated. Labeling of membrane attains the steady-state level by 10 sec at 0 degrees C, and is rapidly reversed by adenosine diphosphate (ADP), K+ decreases the amount of membrane-bound 32P, mainly by enhancing the rate of dephosphorylation of the 32P-intermediate. Hydroxylamine causes a release of about 90% of 32P bound to the membrane, thus indicating that the 32P-intermediate contains an acyl-phosphate bond. When the labeled plasma membrane is solubilized and electrophoresed on acrylamide gels in the presence of sodium dodecyl sulphate, the radioactivity appears to be largely associated with a single protein fraction of 132,000 +/- 2,000 aarent molecular weight. These features of the macrophage Ca2+-ATPase suggest that the enzyme activity might be part of a surface-localized Ca1+-extrusion system, participating in the regulation of Ca2+-dependent activities of the macrophage.", "contents": "Phosphorprotein intermediate in the Ca2+-dependent ATPase reaction of macrophage plasma membrane. ATPase activity and phosphorylation by [gamma-32P] ATP of isolated plasma membrane of alveolar macorphages are stimulated in a parallel fashion by physiologic concentrations of Ca2+, with half-maximal activating effect of this ion at (3--7) X 10(-7) M. For various membrane preparations, a direct proportionality exists between Ca2+-dependent ATPase activity and amount of 32P incorporated. Labeling of membrane attains the steady-state level by 10 sec at 0 degrees C, and is rapidly reversed by adenosine diphosphate (ADP), K+ decreases the amount of membrane-bound 32P, mainly by enhancing the rate of dephosphorylation of the 32P-intermediate. Hydroxylamine causes a release of about 90% of 32P bound to the membrane, thus indicating that the 32P-intermediate contains an acyl-phosphate bond. When the labeled plasma membrane is solubilized and electrophoresed on acrylamide gels in the presence of sodium dodecyl sulphate, the radioactivity appears to be largely associated with a single protein fraction of 132,000 +/- 2,000 aarent molecular weight. These features of the macrophage Ca2+-ATPase suggest that the enzyme activity might be part of a surface-localized Ca1+-extrusion system, participating in the regulation of Ca2+-dependent activities of the macrophage."} {"id": "PMID:159984", "title": "Electrocardiographic voltage changes during hyperthyroidism.", "content": "Electrocardiograms of 67 thyrotoxic patients were studied. Subsequent electrocardiograms during euthyroidism in 16 patients permitted an analysis of voltage changes. Decreases in voltages after radioiodine therapy were significant (P less than 0.01) for the P wave in lead, V1, R wave in leads II, AVF, V4, V5, and V6, maximal RS wave, and maximal R wave and were present in all but one patient. Criteria for left ventricular hypertrophy (sum of S wave in V1 plus R wave in V5 or V6 greater than 35 mm), present in 21% of patients, regressed in all five patients who had later electrocardiograms during euthyroidism. Left ventricular hypertrophy or high-voltage R waves in the absence of usual causes may suggest the presence of hyperthyroidism. The concept that cardiac voltage is determined in part by thyroid hormone is reviewed; this relationship may be the basis for increased voltage in hyperthyroidism as well as decreased voltage in hypothyroidism.", "contents": "Electrocardiographic voltage changes during hyperthyroidism. Electrocardiograms of 67 thyrotoxic patients were studied. Subsequent electrocardiograms during euthyroidism in 16 patients permitted an analysis of voltage changes. Decreases in voltages after radioiodine therapy were significant (P less than 0.01) for the P wave in lead, V1, R wave in leads II, AVF, V4, V5, and V6, maximal RS wave, and maximal R wave and were present in all but one patient. Criteria for left ventricular hypertrophy (sum of S wave in V1 plus R wave in V5 or V6 greater than 35 mm), present in 21% of patients, regressed in all five patients who had later electrocardiograms during euthyroidism. Left ventricular hypertrophy or high-voltage R waves in the absence of usual causes may suggest the presence of hyperthyroidism. The concept that cardiac voltage is determined in part by thyroid hormone is reviewed; this relationship may be the basis for increased voltage in hyperthyroidism as well as decreased voltage in hypothyroidism."} {"id": "PMID:159985", "title": "On the enzymatic response to injury and its mediators.", "content": "The enzymatic response to injury appears as an increase in enzymatic activity in the periphery of burns and other injuries. The following processes constitute the enzymatic response: 1) release, 2) activation and 3) synthesis of enzymes. Processes 2) and 3) are dependent upon the fibroblast, which is an activated fibrocyte. Among the fibrocyte activators, and thus among the mediators of the enzymatic response, are histamine, serotonin, kinins, prostaglandins etc. The effects of non-steroidal anti-inflammatory drugs on the enzymatic response to burn injury were studied. Indomethacin, mefenamic acid or aspirin, suspended in carboxymethylcellulose, were given to rats by stomach tube. Controls received carboxymethylcellulose only. Circular burns were inflicted on anaesthetized animals which were killed 30 min, 2 h or 4 h after burning. The burns were studied histologically and enzyme histochemically by using the methods for prostaglandin synthetase, esterases, and adenosine triphosphatase. Aspirin had no effect on the enzymatic response. Mefenamic acid and indomethacin caused a less severe enzymatic response in the 4-h groups as compared to control rats.", "contents": "On the enzymatic response to injury and its mediators. The enzymatic response to injury appears as an increase in enzymatic activity in the periphery of burns and other injuries. The following processes constitute the enzymatic response: 1) release, 2) activation and 3) synthesis of enzymes. Processes 2) and 3) are dependent upon the fibroblast, which is an activated fibrocyte. Among the fibrocyte activators, and thus among the mediators of the enzymatic response, are histamine, serotonin, kinins, prostaglandins etc. The effects of non-steroidal anti-inflammatory drugs on the enzymatic response to burn injury were studied. Indomethacin, mefenamic acid or aspirin, suspended in carboxymethylcellulose, were given to rats by stomach tube. Controls received carboxymethylcellulose only. Circular burns were inflicted on anaesthetized animals which were killed 30 min, 2 h or 4 h after burning. The burns were studied histologically and enzyme histochemically by using the methods for prostaglandin synthetase, esterases, and adenosine triphosphatase. Aspirin had no effect on the enzymatic response. Mefenamic acid and indomethacin caused a less severe enzymatic response in the 4-h groups as compared to control rats."} {"id": "PMID:159997", "title": "Partial purification and characterization of the phosphate transporter from bovine heart mitochondria.", "content": "A highly active phosphate transporter was extracted with octylglucoside from bovine heart submitochondrial particles that were first partially depleted of other membrane components. It was then partially purified by ammonium sulfate fractionation. After reconstitution of the transporter into liposomes prepared with a crude mixture of soybean phospholipids, the Pi/OH exchange, but not the Pi/Pi exchange, was stimulated three- to fourfold by valinomycin and nigericin in the presence of K+. Both Pi/OH and Pi/Pi exchange activities were sensitive to mercurials and other SH reagents. The rutamycin-sensitive ATPase complex from mitochondria was reconstituted together with the phosphate transporter and adenine nucleotide transporter into liposomes. After inhibition of externally located ATPase, the hydrolysis of ATP was sensitive to atractyloside and mersalyl.", "contents": "Partial purification and characterization of the phosphate transporter from bovine heart mitochondria. A highly active phosphate transporter was extracted with octylglucoside from bovine heart submitochondrial particles that were first partially depleted of other membrane components. It was then partially purified by ammonium sulfate fractionation. After reconstitution of the transporter into liposomes prepared with a crude mixture of soybean phospholipids, the Pi/OH exchange, but not the Pi/Pi exchange, was stimulated three- to fourfold by valinomycin and nigericin in the presence of K+. Both Pi/OH and Pi/Pi exchange activities were sensitive to mercurials and other SH reagents. The rutamycin-sensitive ATPase complex from mitochondria was reconstituted together with the phosphate transporter and adenine nucleotide transporter into liposomes. After inhibition of externally located ATPase, the hydrolysis of ATP was sensitive to atractyloside and mersalyl."} {"id": "PMID:159998", "title": "A new method of preparing Ca2+-ATPase from sarcoplasmic reticulum: extraction with octylglucoside.", "content": "A fast method for preparing Ca2+-ATPase from rabbit muscle sarcoplasmic reticulum was devised. The method involves extracting extrinsic membrane proteins with the non-ionic detergent octylglucoside at high salt concentration. A Ca2+-ATPase of consistently high specific activity (about 25 mumoles/mg.min) is found in the insoluble residue. The method was optimized with respect to the concentrations of detergent and salt, pH, and other extraction conditions. By the criteria of the protein pattern in SDS-polyacrylamide gel electrophoresis, dependence of the hydrolytic activity on the presence of Ca2+, and the phosphoprotein formation, the preparation is identical with the Ca2+-ATPase isolated previously by MacLennan [10] and other authors. The main advantages of the new method are its rapidity, its reliability, and the high specific activity of the purified enzyme.", "contents": "A new method of preparing Ca2+-ATPase from sarcoplasmic reticulum: extraction with octylglucoside. A fast method for preparing Ca2+-ATPase from rabbit muscle sarcoplasmic reticulum was devised. The method involves extracting extrinsic membrane proteins with the non-ionic detergent octylglucoside at high salt concentration. A Ca2+-ATPase of consistently high specific activity (about 25 mumoles/mg.min) is found in the insoluble residue. The method was optimized with respect to the concentrations of detergent and salt, pH, and other extraction conditions. By the criteria of the protein pattern in SDS-polyacrylamide gel electrophoresis, dependence of the hydrolytic activity on the presence of Ca2+, and the phosphoprotein formation, the preparation is identical with the Ca2+-ATPase isolated previously by MacLennan [10] and other authors. The main advantages of the new method are its rapidity, its reliability, and the high specific activity of the purified enzyme."} {"id": "PMID:159999", "title": "Characterization of lambdapolA transducing phages; effective expression of the E. coli polA gene.", "content": "lambdapolA phages carrying the polA gene in either orientation were isolated and characterised by genetic tests and by assay of the polA gene product after infection of E. coli or induction of lysogens. Lytic infection gave consistently better amplification of DNA polymerase I than that obtained by induction of a lysogen. Optimal amplification of DNA polymerase I was not achieved from the PL promoter of cro-phages, but some advantages accrued when the polA gene was oriented for transcription from the PL promoter of a cro+ phage. lambdapolA phages in which the polA allele was from E. coli strain C600 provided better amplification than phages with the polA allele from E. coli ED8659. Induction of a lambdapolA1 cI857 Qam Sam prophage gave levels of DNA polymerase I approaching 100 times that found in the non-lysogenic Pol+ host. Genetics studies with the lambdapolA phages confirmed the previously postulated orientation of the polA gene within the E. coli genome.", "contents": "Characterization of lambdapolA transducing phages; effective expression of the E. coli polA gene. lambdapolA phages carrying the polA gene in either orientation were isolated and characterised by genetic tests and by assay of the polA gene product after infection of E. coli or induction of lysogens. Lytic infection gave consistently better amplification of DNA polymerase I than that obtained by induction of a lysogen. Optimal amplification of DNA polymerase I was not achieved from the PL promoter of cro-phages, but some advantages accrued when the polA gene was oriented for transcription from the PL promoter of a cro+ phage. lambdapolA phages in which the polA allele was from E. coli strain C600 provided better amplification than phages with the polA allele from E. coli ED8659. Induction of a lambdapolA1 cI857 Qam Sam prophage gave levels of DNA polymerase I approaching 100 times that found in the non-lysogenic Pol+ host. Genetics studies with the lambdapolA phages confirmed the previously postulated orientation of the polA gene within the E. coli genome."} {"id": "PMID:160000", "title": "Characterization of the dnaA, gyrB and other genes in the dnaA region of the Escherichia coli chromosome on specialized transducing phages lambda tna.", "content": "Specialized transducing phages lambda tna (tryptophanase) harboring chromosomal DNA and genetic markers from the dnaA region of the Escherichia coli chromosome were isolated. Transductional analysis showed that some of these tnaA transducing phages carry two genes important in DNA replication, namely the dnaA gene (initiation of chromosome replication) and the gyrB gene (subunit B of DNA gyrase), formerly designated couR. The following clockwise order of genetic markers was found: uhp, gyrB, dnaA, rimA, tnaA, bglB. The gene-protein relationship was established by the determination of the gene products encoded on the chromosomal DNA of the different lambda tna. A 54 kD and a 91 kD polypeptide appear to be coded for by the dnaA and gyrB genes, respectively; the 91 kD protein is encoded on a region in which coumermycin sensitivity maps and is with respect to electrophoretic behavior identical to subunit B of DNA gyrase. The 54 kD protein is encoded on the region in which different independently isolated dnaA(Ts) mutations (dnaA5, dnaA46, dnaA167, dnaA203, dnaA204, dnaA205, dnaA211, dnaA508) are located. Additional genes which code for polypeptides with hitherto unknown functions were identified and mapped. The acriflavin sensitivity mutation acrB1 was found to be an allele of the gyrB gene (see \"Note Added in Proof\").", "contents": "Characterization of the dnaA, gyrB and other genes in the dnaA region of the Escherichia coli chromosome on specialized transducing phages lambda tna. Specialized transducing phages lambda tna (tryptophanase) harboring chromosomal DNA and genetic markers from the dnaA region of the Escherichia coli chromosome were isolated. Transductional analysis showed that some of these tnaA transducing phages carry two genes important in DNA replication, namely the dnaA gene (initiation of chromosome replication) and the gyrB gene (subunit B of DNA gyrase), formerly designated couR. The following clockwise order of genetic markers was found: uhp, gyrB, dnaA, rimA, tnaA, bglB. The gene-protein relationship was established by the determination of the gene products encoded on the chromosomal DNA of the different lambda tna. A 54 kD and a 91 kD polypeptide appear to be coded for by the dnaA and gyrB genes, respectively; the 91 kD protein is encoded on a region in which coumermycin sensitivity maps and is with respect to electrophoretic behavior identical to subunit B of DNA gyrase. The 54 kD protein is encoded on the region in which different independently isolated dnaA(Ts) mutations (dnaA5, dnaA46, dnaA167, dnaA203, dnaA204, dnaA205, dnaA211, dnaA508) are located. Additional genes which code for polypeptides with hitherto unknown functions were identified and mapped. The acriflavin sensitivity mutation acrB1 was found to be an allele of the gyrB gene (see \"Note Added in Proof\")."} {"id": "PMID:160001", "title": "Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. II. Further evidence for a novel function in error-prone repair.", "content": "Uvm mutants of Escherichia coli K12 selected for defective UV reversion induction have previously been reported to differ considerably from the UV-reversion-less recA and lexA mutants with regard to survival or mutagenic response to UV, X-rays and alkylating agents. In the present study, the phenotypic characterization of uvm mutants was extended to investigate several cellular processes which also may be related to or involved in UV mutagenesis. Like recA and lexA mutations, the uvm mutations exhibit highly reduced Weigle reactivation and normal host cell reactivation of UV irradiated phage lambda. But unlike recA and lexA, the uvm mutations do not impair genetic recombination, UV induction of prophage lambda or R plasmid-mediated UV resistance and mutagenesis. These phenotypical characteristics and preliminary results of genetic mapping lend further support to the assumption that the uvm site may be a novel locus affecting, apart from the recA and lexA loci, the error-prone repair pathway in E. coli.", "contents": "Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. II. Further evidence for a novel function in error-prone repair. Uvm mutants of Escherichia coli K12 selected for defective UV reversion induction have previously been reported to differ considerably from the UV-reversion-less recA and lexA mutants with regard to survival or mutagenic response to UV, X-rays and alkylating agents. In the present study, the phenotypic characterization of uvm mutants was extended to investigate several cellular processes which also may be related to or involved in UV mutagenesis. Like recA and lexA mutations, the uvm mutations exhibit highly reduced Weigle reactivation and normal host cell reactivation of UV irradiated phage lambda. But unlike recA and lexA, the uvm mutations do not impair genetic recombination, UV induction of prophage lambda or R plasmid-mediated UV resistance and mutagenesis. These phenotypical characteristics and preliminary results of genetic mapping lend further support to the assumption that the uvm site may be a novel locus affecting, apart from the recA and lexA loci, the error-prone repair pathway in E. coli."} {"id": "PMID:160002", "title": "The surface layer of Candida albicans.", "content": "The surface of Candida albicans is covered by a mucus layer secreted by the cell. Excess mucus secretion accumulates between the cells, and contains protein, polysaccharides and secreted enzymes. In mature cultures dead cells are trapped in the mucus, and the accumulated mucus and cell debris facilitate the formation of plaque, and the penetration of C. albicans into infected host tissues.", "contents": "The surface layer of Candida albicans. The surface of Candida albicans is covered by a mucus layer secreted by the cell. Excess mucus secretion accumulates between the cells, and contains protein, polysaccharides and secreted enzymes. In mature cultures dead cells are trapped in the mucus, and the accumulated mucus and cell debris facilitate the formation of plaque, and the penetration of C. albicans into infected host tissues."} {"id": "PMID:160003", "title": "The influences of a lambda prophage on the growth rate of Escherichia coli.", "content": "A lambda prophage increases the competitive ability of E. coli K12 in a glucose-limited chemostat. This phenomenon does not involve the lambdarex gene. Expression of the lambdarex gene conditionally decreases fitness in two ways: (1) it causes malT- but not malT+ lysogens to be at a selective disadvantage in competition with non-lysogens. (2) During adaptation to slow, glucose-limited chemostat growth from rapid, glucose-excess flask growth, expression of the lambdarex gene transiently decreases the growth rate when compared to the non-lysogen.", "contents": "The influences of a lambda prophage on the growth rate of Escherichia coli. A lambda prophage increases the competitive ability of E. coli K12 in a glucose-limited chemostat. This phenomenon does not involve the lambdarex gene. Expression of the lambdarex gene conditionally decreases fitness in two ways: (1) it causes malT- but not malT+ lysogens to be at a selective disadvantage in competition with non-lysogens. (2) During adaptation to slow, glucose-limited chemostat growth from rapid, glucose-excess flask growth, expression of the lambdarex gene transiently decreases the growth rate when compared to the non-lysogen."} {"id": "PMID:160005", "title": "Plasma exchange: a selective form of blood-letting.", "content": "The technique of, and indications for, plasma exchange are presented. This selective form of plasma removal has re-established \"blood-letting\" in medical therapeutics on a scientific basis. It is the most appropriate therapy when hyperviscosity or haemostatic failure complicate immunoproliferative disease. Plasma exchange is also a significant advance in the management of fulminant forms of autoimmune disease, but in many other conditions it must be regarded as experimental.", "contents": "Plasma exchange: a selective form of blood-letting. The technique of, and indications for, plasma exchange are presented. This selective form of plasma removal has re-established \"blood-letting\" in medical therapeutics on a scientific basis. It is the most appropriate therapy when hyperviscosity or haemostatic failure complicate immunoproliferative disease. Plasma exchange is also a significant advance in the management of fulminant forms of autoimmune disease, but in many other conditions it must be regarded as experimental."} {"id": "PMID:160012", "title": "Regular steps in bending cilia during the effective stroke.", "content": "A ciliary beat cycle consists of an effective stroke in which the extended cilium makes an oar-like movement towards one side, and a recovery stroke in which the cilium moves back by propagating a bend from base to tip (Fig. 1A). In the sliding microtubule model of ciliary and flagellar movement, which is now supported by substantial evidence1-3, the sliding displacement of microtubules in any region of the cilium is related linearly to the angular change in the direction of that region (Fig. 1B). Thus, during the effective stroke, microtubule sliding is not confined to the region near the base of the cilium but involves the whole length of the extended organelle, and the relative speed of sliding can be measured as the angular velocity of the ciliary motion. I report here that in molluscan cilia the effective stroke consists of regularly alternating rapid and slow phases of angular movement. This suggests that the microtubules slide in quantal steps.", "contents": "Regular steps in bending cilia during the effective stroke. A ciliary beat cycle consists of an effective stroke in which the extended cilium makes an oar-like movement towards one side, and a recovery stroke in which the cilium moves back by propagating a bend from base to tip (Fig. 1A). In the sliding microtubule model of ciliary and flagellar movement, which is now supported by substantial evidence1-3, the sliding displacement of microtubules in any region of the cilium is related linearly to the angular change in the direction of that region (Fig. 1B). Thus, during the effective stroke, microtubule sliding is not confined to the region near the base of the cilium but involves the whole length of the extended organelle, and the relative speed of sliding can be measured as the angular velocity of the ciliary motion. I report here that in molluscan cilia the effective stroke consists of regularly alternating rapid and slow phases of angular movement. This suggests that the microtubules slide in quantal steps."} {"id": "PMID:160010", "title": "Motor neuron firing range, axonal conduction velocity, and muscle fiber histochemistry in neuromuscular diseases.", "content": "The voluntary discharge properties and axonal conduction velocity of single motor units were studied in patients with neuromuscular diseases with retained differentiation of the muscle fibers into type 1 and type 2, and in patients with late-onset hereditary distal myopathy in which muscle fibers have only intermediate histochemical properties. In the patients with muscle fiber differentiation, the findings were similar to those in normal subjects; that is, there was a continuum between motor units which fired tonically at low rates and had a low axonal conduction velocity, and motor units which fired phasically at high rates and had a high axonal conduction velocity. In the patients without muscle fiber differentiation, all motor units had intermediate firing properties and a low axonal conduction velocity. It is suggested that in chronic pathologic states, the differentiation of the muscle fiber histochemistry remains only as long as the differentiation of the motor neurons remains.", "contents": "Motor neuron firing range, axonal conduction velocity, and muscle fiber histochemistry in neuromuscular diseases. The voluntary discharge properties and axonal conduction velocity of single motor units were studied in patients with neuromuscular diseases with retained differentiation of the muscle fibers into type 1 and type 2, and in patients with late-onset hereditary distal myopathy in which muscle fibers have only intermediate histochemical properties. In the patients with muscle fiber differentiation, the findings were similar to those in normal subjects; that is, there was a continuum between motor units which fired tonically at low rates and had a low axonal conduction velocity, and motor units which fired phasically at high rates and had a high axonal conduction velocity. In the patients without muscle fiber differentiation, all motor units had intermediate firing properties and a low axonal conduction velocity. It is suggested that in chronic pathologic states, the differentiation of the muscle fiber histochemistry remains only as long as the differentiation of the motor neurons remains."} {"id": "PMID:160011", "title": "Types of human intrafusal muscle fibers.", "content": "The histochemical and fine structural profiles of human intrafusal muscle fibers were studied. Spindles were located in freshly frozen specimens taken from biopsied normal external intercostal muscles, and periodic 10- and 50-mum-thick cross sections were processed alternately for enzyme histochemical and electron microscopic examination. Nuclear bag fibers were of two types, bag1 and bag2, histochemically, and they displayed two distinct types of ultrastructure. Nuclear chain fibers were histochemically and ultrastructurally homogeneous. Regional differences in enzymatic staining and ultrastructure occurred along individual intrafusal fibers. Human bag1 and bag2 fibers appear to be analogous to the two types of nuclear bag fiber identified in animal spindles and are considered to have different roles in spindle function. The presence of three types of intrafusal fibers should be taken into account when studying spindle abnormalities in human neuromuscular disorders.", "contents": "Types of human intrafusal muscle fibers. The histochemical and fine structural profiles of human intrafusal muscle fibers were studied. Spindles were located in freshly frozen specimens taken from biopsied normal external intercostal muscles, and periodic 10- and 50-mum-thick cross sections were processed alternately for enzyme histochemical and electron microscopic examination. Nuclear bag fibers were of two types, bag1 and bag2, histochemically, and they displayed two distinct types of ultrastructure. Nuclear chain fibers were histochemically and ultrastructurally homogeneous. Regional differences in enzymatic staining and ultrastructure occurred along individual intrafusal fibers. Human bag1 and bag2 fibers appear to be analogous to the two types of nuclear bag fiber identified in animal spindles and are considered to have different roles in spindle function. The presence of three types of intrafusal fibers should be taken into account when studying spindle abnormalities in human neuromuscular disorders."} {"id": "PMID:160013", "title": "Inhibition of mixed lymphocyte response by monoclonal antibody specific for a rat T lymphocyte subset.", "content": "Cell-surface differentiation antigens which are associated with particular lymphocyte subsets are likely to be molecules which mediate specific functions of the cells which display them. One way to investigate this hypothesis is to see whether antibodies directed against such antigens will inhibit functional systems. This approach can be attempted with confidence if monoclonal antibodies are used, as these react with one antigenic determinant only and can be used in purified form. In this report we show that a monoclonal antibody which is specific for a subset of rat tT lymphocytes inhibits the mixed lymphocyte response (MLR). The antibody acts on the responder cells without killing them.", "contents": "Inhibition of mixed lymphocyte response by monoclonal antibody specific for a rat T lymphocyte subset. Cell-surface differentiation antigens which are associated with particular lymphocyte subsets are likely to be molecules which mediate specific functions of the cells which display them. One way to investigate this hypothesis is to see whether antibodies directed against such antigens will inhibit functional systems. This approach can be attempted with confidence if monoclonal antibodies are used, as these react with one antigenic determinant only and can be used in purified form. In this report we show that a monoclonal antibody which is specific for a subset of rat tT lymphocytes inhibits the mixed lymphocyte response (MLR). The antibody acts on the responder cells without killing them."} {"id": "PMID:160016", "title": "Alterations of mitochondrial properties in folate nephropathy.", "content": "Folate nephropathy was selected as a model to study renal mitochondrial response after tubular injury. 20 h after injection, 14C-leucine incorporation was suppressed to 20--30% of control, 14C-mannose incorporation was 63--78% greater than control while the activities of succinic dehydrogenase and monoamine oxidase were unaltered. By 40 h, 14C-leucine incorporation had been restored to control values. Also, at 20 h, ATPase activity sensitive to oligomycin inhibition had increased by 45--73%, whereas K+-stimulated ATPase activity was reduced in the experimental mitochondrial fractions. The results are discussed along with other studies of mitochondria in experimental renal disease.", "contents": "Alterations of mitochondrial properties in folate nephropathy. Folate nephropathy was selected as a model to study renal mitochondrial response after tubular injury. 20 h after injection, 14C-leucine incorporation was suppressed to 20--30% of control, 14C-mannose incorporation was 63--78% greater than control while the activities of succinic dehydrogenase and monoamine oxidase were unaltered. By 40 h, 14C-leucine incorporation had been restored to control values. Also, at 20 h, ATPase activity sensitive to oligomycin inhibition had increased by 45--73%, whereas K+-stimulated ATPase activity was reduced in the experimental mitochondrial fractions. The results are discussed along with other studies of mitochondria in experimental renal disease."} {"id": "PMID:160021", "title": "A controlled trial of manipulation in a selected group of patients with low back pain favouring one side.", "content": "Ten patients with low back pain favouring mainly one side are treated by manipulation, using a specified technique. Tension measurements in both legs are taken at five degree increments as the legs are passively raised, with the knees extended, both before and after manipulation. The resultant tension gradients are compared with a control group of subjects with no back pain who are also manipulated. There is a statistically significant alteration in the tension measurements after manipulation of the painful side as compared with the change after manipulation of the controls.", "contents": "A controlled trial of manipulation in a selected group of patients with low back pain favouring one side. Ten patients with low back pain favouring mainly one side are treated by manipulation, using a specified technique. Tension measurements in both legs are taken at five degree increments as the legs are passively raised, with the knees extended, both before and after manipulation. The resultant tension gradients are compared with a control group of subjects with no back pain who are also manipulated. There is a statistically significant alteration in the tension measurements after manipulation of the painful side as compared with the change after manipulation of the controls."} {"id": "PMID:160022", "title": "Achievement by the genetically disabled: a history of social and medical aid to a patient with partial Down's syndrome.", "content": "A trisomy 21/normal mosaic is described, together with her educational and social development. Amniocentesis was used to monitor her two pregnancies and both fetuses were found to be normal. Social and medical aid have encouraged the patient to lead a normal life.", "contents": "Achievement by the genetically disabled: a history of social and medical aid to a patient with partial Down's syndrome. A trisomy 21/normal mosaic is described, together with her educational and social development. Amniocentesis was used to monitor her two pregnancies and both fetuses were found to be normal. Social and medical aid have encouraged the patient to lead a normal life."} {"id": "PMID:160025", "title": "Needle tract endometriosis: an unusual complication of amniocentesis.", "content": "A case is presented of abdominal wall endometriosis following amniocentesis. A discussion of this unusual phenomenon is included.", "contents": "Needle tract endometriosis: an unusual complication of amniocentesis. A case is presented of abdominal wall endometriosis following amniocentesis. A discussion of this unusual phenomenon is included."} {"id": "PMID:160030", "title": "Pathology of dementia.", "content": "A group of diseases of the brain characterized by dementia have been discussed. The pathologic features of each were described and illustrated. It seems that, in summary, several points merit emphasis. First of all, as more people survive to the seventh, eighth, and ninth decades, the most common dementia, senile Alzheimer's disease, will become a more significant public health problem. Second, while at the present time there is no successful therapy available, there are some glimmerings of hope on the horizon. The discovery of the agent of Creutzfeldt-Jakob disease seems to have placed us on the fringe of a whole new series of advances. A novel type of disease agent awaits characterization and definition, and there are hints that similar agents could be responsible for the development of the degenerative diseases, perhaps in conjunction with environmental toxins and in the medium of a permissive genetic background. In the case of Huntington's chorea, it seems reasonable that a pharmacologic agent could be found to control the symptoms such as L-dopa therapy has done for patients with Parkinson's disease. It may develop, however, that such an agent will control the choreiform movements but will not influence the dementing condition.", "contents": "Pathology of dementia. A group of diseases of the brain characterized by dementia have been discussed. The pathologic features of each were described and illustrated. It seems that, in summary, several points merit emphasis. First of all, as more people survive to the seventh, eighth, and ninth decades, the most common dementia, senile Alzheimer's disease, will become a more significant public health problem. Second, while at the present time there is no successful therapy available, there are some glimmerings of hope on the horizon. The discovery of the agent of Creutzfeldt-Jakob disease seems to have placed us on the fringe of a whole new series of advances. A novel type of disease agent awaits characterization and definition, and there are hints that similar agents could be responsible for the development of the degenerative diseases, perhaps in conjunction with environmental toxins and in the medium of a permissive genetic background. In the case of Huntington's chorea, it seems reasonable that a pharmacologic agent could be found to control the symptoms such as L-dopa therapy has done for patients with Parkinson's disease. It may develop, however, that such an agent will control the choreiform movements but will not influence the dementing condition."} {"id": "PMID:160026", "title": "Assessing skin problems of occupational origin.", "content": "Severity of occupational cutaneous hazards depends on the agent's harmfulness, kind of exposure, the affected subject's responsiveness, and the controls in effect.", "contents": "Assessing skin problems of occupational origin. Severity of occupational cutaneous hazards depends on the agent's harmfulness, kind of exposure, the affected subject's responsiveness, and the controls in effect."} {"id": "PMID:160031", "title": "Fetal properties in red blood cells of newborn infants.", "content": "In order to identify the fetal features in neonatal erythrocytes, cord blood was separated into seven fractions of varying specific density. Cell age in the single fractions was ascertained by means of reticulocyte count, glutamic-oxalacetic transaminase activity, and hemoglobin F concentration. The same procedures were used with blood of adults. With the exception of the fraction of neonatal blood with the highest specific density, the blood from neonates and adults correlated well for cell age and specific density. The highest specific density fraction of neonatal blood was found to contain a higher proportion of younger cells. The comparison of enzyme activities in the single fractions between neonates and adults showed that a high activity of glucose-6-phosphatedehydrogenase and enolase and a low activity of phosphofructokinase are typical fetal signs of neonatal cells.", "contents": "Fetal properties in red blood cells of newborn infants. In order to identify the fetal features in neonatal erythrocytes, cord blood was separated into seven fractions of varying specific density. Cell age in the single fractions was ascertained by means of reticulocyte count, glutamic-oxalacetic transaminase activity, and hemoglobin F concentration. The same procedures were used with blood of adults. With the exception of the fraction of neonatal blood with the highest specific density, the blood from neonates and adults correlated well for cell age and specific density. The highest specific density fraction of neonatal blood was found to contain a higher proportion of younger cells. The comparison of enzyme activities in the single fractions between neonates and adults showed that a high activity of glucose-6-phosphatedehydrogenase and enolase and a low activity of phosphofructokinase are typical fetal signs of neonatal cells."} {"id": "PMID:160033", "title": "Nucleotide sequence of a secondary attachment site for bacteriophage lambda on the Escherichia coli chromosome.", "content": "The nucleotide sequence of a secondary attachment site for bacteriophage lambda was determined in a region near the rrnB gene at 88 min on the E. coli chromosome. The sequence has a 8 base pair interrupted homology GCT TTTTA to the common core of the primary attachment site (attB) and the corresponding phage sequence (attP). The site of crossover during integration lies probably between nucleotides -3 and +1. The flanking regions have no obvious homology to the arms of either attP or attB.", "contents": "Nucleotide sequence of a secondary attachment site for bacteriophage lambda on the Escherichia coli chromosome. The nucleotide sequence of a secondary attachment site for bacteriophage lambda was determined in a region near the rrnB gene at 88 min on the E. coli chromosome. The sequence has a 8 base pair interrupted homology GCT TTTTA to the common core of the primary attachment site (attB) and the corresponding phage sequence (attP). The site of crossover during integration lies probably between nucleotides -3 and +1. The flanking regions have no obvious homology to the arms of either attP or attB."} {"id": "PMID:160028", "title": "[Flea fauna and ecology of jerboas in the southern Balkhash region (Aphaniptera)].", "content": "22 species of fleas have been found on five species of jerboa in southern Pribalkhashje. Of them 8 species are parasites of jerboa, 13 -- of gerbils and one -- of birds. Most abundant are three species of fleas of jerboa: M. lenis, M. eucta and O. volgensis. Of gerbils' fleas representatives of the genus Xenopsylla were dominant on jerboa. The greatest indices of abundance have been reported for A. severtzovi, A. elator, A. acontion. The gerbils' fleas are more abundant on D. sagitta than on the other species.", "contents": "[Flea fauna and ecology of jerboas in the southern Balkhash region (Aphaniptera)]. 22 species of fleas have been found on five species of jerboa in southern Pribalkhashje. Of them 8 species are parasites of jerboa, 13 -- of gerbils and one -- of birds. Most abundant are three species of fleas of jerboa: M. lenis, M. eucta and O. volgensis. Of gerbils' fleas representatives of the genus Xenopsylla were dominant on jerboa. The greatest indices of abundance have been reported for A. severtzovi, A. elator, A. acontion. The gerbils' fleas are more abundant on D. sagitta than on the other species."} {"id": "PMID:160047", "title": "Prenatal exposure to testosterone and its precursors influences morphology and later behavioral responsiveness to testosterone of female mice.", "content": "Prenatal exposure to testosterone (T), dehydroepiandrosterone or progesterone significantly increased ano-genital distance of female mice. In addition, prenatal exposure to T or pregnenolone significantly reduced the duration of T exposure during adult life required to induce intraspecific fighting behavior. However, the most masculinized females, those exposed to T prenatally, still had significantly shorter ano-genital distances and required a longer exposure period to T in order to establish fighting than did prenatally oil-exposed male mice. Additional experiments revealed that pregnenolone augments later responsiveness to the aggression-promoting property of T only if it is administered during the prenatal period of development.", "contents": "Prenatal exposure to testosterone and its precursors influences morphology and later behavioral responsiveness to testosterone of female mice. Prenatal exposure to testosterone (T), dehydroepiandrosterone or progesterone significantly increased ano-genital distance of female mice. In addition, prenatal exposure to T or pregnenolone significantly reduced the duration of T exposure during adult life required to induce intraspecific fighting behavior. However, the most masculinized females, those exposed to T prenatally, still had significantly shorter ano-genital distances and required a longer exposure period to T in order to establish fighting than did prenatally oil-exposed male mice. Additional experiments revealed that pregnenolone augments later responsiveness to the aggression-promoting property of T only if it is administered during the prenatal period of development."} {"id": "PMID:160048", "title": "Cataractogenic and lethal effect of selenite in rats during postnatal ontogenesis.", "content": "Male rats aged 5, 10, 15, 20, 30, 40, 50 and 60 days were injected with a single dose of sodium selenite (20 or 40 mumol/kg b.w.). For two months after the injection, all the rats were observed daily for mortality (acute up to 24 h after the injection, subacute 2--7 days after) and the incidence of permanent and intermittent cataract. With the higher dose, both forms of lethal effect were found to shift to earlier phases of ontogenetic development, subacute mortality appearing sooner than acute mortality. The cataractogenic effect produced by the administration of both 20 and 40 mumol/kg b.w. dependent on the age of the experimental animals. It appeared only in the early phases of ontogenetic development (up to the age of 15 days); cataract was not observed during later development.", "contents": "Cataractogenic and lethal effect of selenite in rats during postnatal ontogenesis. Male rats aged 5, 10, 15, 20, 30, 40, 50 and 60 days were injected with a single dose of sodium selenite (20 or 40 mumol/kg b.w.). For two months after the injection, all the rats were observed daily for mortality (acute up to 24 h after the injection, subacute 2--7 days after) and the incidence of permanent and intermittent cataract. With the higher dose, both forms of lethal effect were found to shift to earlier phases of ontogenetic development, subacute mortality appearing sooner than acute mortality. The cataractogenic effect produced by the administration of both 20 and 40 mumol/kg b.w. dependent on the age of the experimental animals. It appeared only in the early phases of ontogenetic development (up to the age of 15 days); cataract was not observed during later development."} {"id": "PMID:160049", "title": "Radioimmunoassay of arginine vasopressin in the plasma and urine.", "content": "We introduced the radioimmunoassay (RIA) of arginine vasopressin (AVP) with standard AVP and antiserum to AVP (both Calibiochem). The sensitivity of the system was increased from the declared 4pg to 1 pg per tube by preparing AVP-125I of high specific activity (about 1,500 mCi/mg) and by modifying the reaction conditions. The sensitivity of the method was adequate for measuring AVP in urine and in concentrated plasma extracts, even under physiological conditions. Reliability of the results depended upon maintenance of approximately the same osmolarity in all the RIA samples. The mean plasma AVP level, uncorrected for AVP extraction losses, was 1.52 +/- 0.20 pg/ml for an ad libitum fluid intake; in fluid deprivation it rose in proportion to the osmolarity of the plasma to 5.83 +/- 0.42 pg/ml at 12 hours and to 19.09 +/- 4.51 pg/ml at 36 hours. Extraction recovery of added AVP was about 63%. The urinary AVP concentration varied according to the patients' state of hydratation from undetectable values at UOsm less than 200 mOsm/1 to a mean 16.5 +/- 7.9 pg/ml in the presence of an ad libitum fluid intake and to 29.1 +/- 7.5 pg/ml after 12 hours' and 117.2 +/- 13.7 pg/ml after 36 hours' deprivation of fluids.", "contents": "Radioimmunoassay of arginine vasopressin in the plasma and urine. We introduced the radioimmunoassay (RIA) of arginine vasopressin (AVP) with standard AVP and antiserum to AVP (both Calibiochem). The sensitivity of the system was increased from the declared 4pg to 1 pg per tube by preparing AVP-125I of high specific activity (about 1,500 mCi/mg) and by modifying the reaction conditions. The sensitivity of the method was adequate for measuring AVP in urine and in concentrated plasma extracts, even under physiological conditions. Reliability of the results depended upon maintenance of approximately the same osmolarity in all the RIA samples. The mean plasma AVP level, uncorrected for AVP extraction losses, was 1.52 +/- 0.20 pg/ml for an ad libitum fluid intake; in fluid deprivation it rose in proportion to the osmolarity of the plasma to 5.83 +/- 0.42 pg/ml at 12 hours and to 19.09 +/- 4.51 pg/ml at 36 hours. Extraction recovery of added AVP was about 63%. The urinary AVP concentration varied according to the patients' state of hydratation from undetectable values at UOsm less than 200 mOsm/1 to a mean 16.5 +/- 7.9 pg/ml in the presence of an ad libitum fluid intake and to 29.1 +/- 7.5 pg/ml after 12 hours' and 117.2 +/- 13.7 pg/ml after 36 hours' deprivation of fluids."} {"id": "PMID:160059", "title": "[A study of the tensile strength of cruciate ligaments with regard to the possibilities of prosthetic replacement (author's transl)].", "content": "Recent clinical and experimental results in the prosthetic replacement of the anterior cruciate ligament are minimal and this fact has incited us to search for additional fundamental characteristics of natural and synthetic ligaments. The dissection of over 30 human knees (5 fresh and 27 embalmed specimens), of 50 dog knees and of 20 cat knees showed that the posterior cruciate ligament was longer and of bigger size than the anterior cruciate ligament. In dogs, the anatomo-radiological study showed a lenghtening of 14,4 p. 100 for the anterior cruciate and of 10,5 p. 1u0 for the posterior cruciate ligament in the various goniometric positions. Traction with the Instron apparatus using whole knee with preserved bony attachments revealed an elastic resistance (yield point) of the ligament of about 50 kg, 60 kg and 30 kg (for human, dog and cat respectively) with elastic elongation (at the yield stress) of 25 p. 100, 35 p. 100 and 45 p. 100 (respectively). Trials on the polyethylene prosthetic ligament used at the present time for replacement of cruciate ligaments in humans showed an elastic resistance of only 16 kg with an elasticity of only 1,4 p. 100. The major differences between the physical properties of the artificial and natural ligaments that we have studied in experimental conditions incite our serious doubt as to the value for the practical use of such a prosthesis and provoque strongly the necessity of search for alternative synthetic or other material more suitable for the task in question.", "contents": "[A study of the tensile strength of cruciate ligaments with regard to the possibilities of prosthetic replacement (author's transl)]. Recent clinical and experimental results in the prosthetic replacement of the anterior cruciate ligament are minimal and this fact has incited us to search for additional fundamental characteristics of natural and synthetic ligaments. The dissection of over 30 human knees (5 fresh and 27 embalmed specimens), of 50 dog knees and of 20 cat knees showed that the posterior cruciate ligament was longer and of bigger size than the anterior cruciate ligament. In dogs, the anatomo-radiological study showed a lenghtening of 14,4 p. 100 for the anterior cruciate and of 10,5 p. 1u0 for the posterior cruciate ligament in the various goniometric positions. Traction with the Instron apparatus using whole knee with preserved bony attachments revealed an elastic resistance (yield point) of the ligament of about 50 kg, 60 kg and 30 kg (for human, dog and cat respectively) with elastic elongation (at the yield stress) of 25 p. 100, 35 p. 100 and 45 p. 100 (respectively). Trials on the polyethylene prosthetic ligament used at the present time for replacement of cruciate ligaments in humans showed an elastic resistance of only 16 kg with an elasticity of only 1,4 p. 100. The major differences between the physical properties of the artificial and natural ligaments that we have studied in experimental conditions incite our serious doubt as to the value for the practical use of such a prosthesis and provoque strongly the necessity of search for alternative synthetic or other material more suitable for the task in question."} {"id": "PMID:160060", "title": "[Upper tibial osteotomy for degenerative arthritis of the knee with varus deformity.-A review of 250 cases. (author's transl)].", "content": "The authors have reviewed 250 cases of upper tibial osteotomy for varus deformity of the knee with degenerative arthritis of the medial compartment. Most of the osteotomies (136) were closing osteotomies, the remainder being opening osteotomies using a bone graft. Closing osteotomy is recommended together with an arthrolysis of the upper tibio-fibular joint instead of a fibular osteotomy. Hyper-correction appeared to be beneficial in cases with lateral ligament laxity. The authors do not recommend intra-articular cartilage shaving or meniscectomy. They advocate surgical release of the patella by division of the lateral patellar retinacula or by anterior displacement of the tibial tuberosity.", "contents": "[Upper tibial osteotomy for degenerative arthritis of the knee with varus deformity.-A review of 250 cases. (author's transl)]. The authors have reviewed 250 cases of upper tibial osteotomy for varus deformity of the knee with degenerative arthritis of the medial compartment. Most of the osteotomies (136) were closing osteotomies, the remainder being opening osteotomies using a bone graft. Closing osteotomy is recommended together with an arthrolysis of the upper tibio-fibular joint instead of a fibular osteotomy. Hyper-correction appeared to be beneficial in cases with lateral ligament laxity. The authors do not recommend intra-articular cartilage shaving or meniscectomy. They advocate surgical release of the patella by division of the lateral patellar retinacula or by anterior displacement of the tibial tuberosity."} {"id": "PMID:160061", "title": "[Compartment syndrome of the leg (author's transl)].", "content": "The authors have observed ten compartment syndromes of the leg. Nine occurred after tibial fractures, one after a contusive trauma. Early signs those of muscular and neural ischemia, with an acute pain when the toes are passively mobilised. The cast must be promptly removed. In 6 cases the two compartments were involved. In all cases the pulses were palpable. Arteriographs could occasionaly verify the integrity of the main arterial trunks. The treatment is based on early fasciotomies. It was realised in 5 cases, with good results when the fasciotomy was realised more than twelve hours after the trauma, the muscles were more or less necrotic. In one case all the muscles of the leg had to be excised.", "contents": "[Compartment syndrome of the leg (author's transl)]. The authors have observed ten compartment syndromes of the leg. Nine occurred after tibial fractures, one after a contusive trauma. Early signs those of muscular and neural ischemia, with an acute pain when the toes are passively mobilised. The cast must be promptly removed. In 6 cases the two compartments were involved. In all cases the pulses were palpable. Arteriographs could occasionaly verify the integrity of the main arterial trunks. The treatment is based on early fasciotomies. It was realised in 5 cases, with good results when the fasciotomy was realised more than twelve hours after the trauma, the muscles were more or less necrotic. In one case all the muscles of the leg had to be excised."} {"id": "PMID:160062", "title": "[A technique of patellectomy preserving the extensor apparatus (author's transl)].", "content": "The Authors describe a technique of patellectomy preserving the extensor apparatus. The lateral and medial patellar ligaments are divided longitudinally, folded forward and sutured to each other anteriorly, the lateral incision being left open. The authors have used this procedure in 11 knees with satisfactory results. It can be combined with plasties of the femoral condylar groove.", "contents": "[A technique of patellectomy preserving the extensor apparatus (author's transl)]. The Authors describe a technique of patellectomy preserving the extensor apparatus. The lateral and medial patellar ligaments are divided longitudinally, folded forward and sutured to each other anteriorly, the lateral incision being left open. The authors have used this procedure in 11 knees with satisfactory results. It can be combined with plasties of the femoral condylar groove."} {"id": "PMID:160063", "title": "[Expanding intramedullary rods in the treatment of osteogenesis imperfecta (author's transl)].", "content": "Eleven cases of osteogenesis imperfecta were treated by corrective osteotomies and fixation with expanding intramedullary rods. The authors have used the Bailey-Dubow nail. Despite a short follow-up (average one year) they think that the device will avoid future repeated changes of rods during the growing period. Several technical pitfalls are described. It is thought that the same technique could be applied to congenital pseudarthrosis of the tibia.", "contents": "[Expanding intramedullary rods in the treatment of osteogenesis imperfecta (author's transl)]. Eleven cases of osteogenesis imperfecta were treated by corrective osteotomies and fixation with expanding intramedullary rods. The authors have used the Bailey-Dubow nail. Despite a short follow-up (average one year) they think that the device will avoid future repeated changes of rods during the growing period. Several technical pitfalls are described. It is thought that the same technique could be applied to congenital pseudarthrosis of the tibia."} {"id": "PMID:160064", "title": "[Massive osteolysis (author's transl)].", "content": "One case involving the scapula and the clavicle is reported. After a 25 years follow-up, the disease was spontaneously non-evolutive.", "contents": "[Massive osteolysis (author's transl)]. One case involving the scapula and the clavicle is reported. After a 25 years follow-up, the disease was spontaneously non-evolutive."} {"id": "PMID:160065", "title": "[Spherical osteotomy (author's transl)].", "content": "The authors have devised a new type of saw which makes it possible to cut bone spherically. This type of osteotomy is useful when correction is required in more than one plane and provides good bone contact between bone ends. The technique is described. It has been used at the upper end of the tibia or femur and in the calcaneus and forefoot.", "contents": "[Spherical osteotomy (author's transl)]. The authors have devised a new type of saw which makes it possible to cut bone spherically. This type of osteotomy is useful when correction is required in more than one plane and provides good bone contact between bone ends. The technique is described. It has been used at the upper end of the tibia or femur and in the calcaneus and forefoot."} {"id": "PMID:160066", "title": "[The use of an original brace in the treatment of kyphosis (author's transl)].", "content": "The authors have designed an original brace which can be used in the treatment of severe and evolutive hyphosis, when kinesitherapy alone is not sufficient. The brace can be removed during the night and for the practice of sports. It is based on the increase of corrective reflexes. A review of 100 cases showed satisfactory results.", "contents": "[The use of an original brace in the treatment of kyphosis (author's transl)]. The authors have designed an original brace which can be used in the treatment of severe and evolutive hyphosis, when kinesitherapy alone is not sufficient. The brace can be removed during the night and for the practice of sports. It is based on the increase of corrective reflexes. A review of 100 cases showed satisfactory results."} {"id": "PMID:160068", "title": "Effect of ipratropium bromide and fenoterol on airway obstruction in chronic pulmonary tuberculosis.", "content": "Single-blind, cross-over comparison of standard doses of ipratropium bromide (2 puffs of 0.02 mg each) and fenoterol (2 puffs of 0.2 mg each) in 36 pairs of experiments in 6 patients with partially reversible airway obstruction, presumably secondary to chronic widespread pulmonary tuberculosis, revealed no difference between the drugs in bronchodilating effect, evaluated by peak-flow measurements and spirometry. The inhalation of isoprenaline at the end of the experiment induced no further improvement in the lung function variables measured. The results suggest that a vagal reflex mechanism plays a major role in bronchoconstriction connected with severe chronic pulmonary tuberculosis.", "contents": "Effect of ipratropium bromide and fenoterol on airway obstruction in chronic pulmonary tuberculosis. Single-blind, cross-over comparison of standard doses of ipratropium bromide (2 puffs of 0.02 mg each) and fenoterol (2 puffs of 0.2 mg each) in 36 pairs of experiments in 6 patients with partially reversible airway obstruction, presumably secondary to chronic widespread pulmonary tuberculosis, revealed no difference between the drugs in bronchodilating effect, evaluated by peak-flow measurements and spirometry. The inhalation of isoprenaline at the end of the experiment induced no further improvement in the lung function variables measured. The results suggest that a vagal reflex mechanism plays a major role in bronchoconstriction connected with severe chronic pulmonary tuberculosis."} {"id": "PMID:160072", "title": "The value of exercises in the treatment of low back pain.", "content": "The results of treatment with short-wave diathermy were compared with those achieved by short-wave diathermy combined with back extension or lumbar isometric flexion exercises in 43 patients with back pain. Subjects were relatively young and normally engaged in sporting activities. Marginally more patients improved amongst those receiving extension exercises. Significant reduction of pain and increase of spinal flexion occurred with each treatment and the periods taken to resume work or sport were similar in each group. Neither exercise regime appeared to have a major influence on recovery. Isometric flexion exercises did not seem to be more beneficial for those with a prominent lumbar lordosis.", "contents": "The value of exercises in the treatment of low back pain. The results of treatment with short-wave diathermy were compared with those achieved by short-wave diathermy combined with back extension or lumbar isometric flexion exercises in 43 patients with back pain. Subjects were relatively young and normally engaged in sporting activities. Marginally more patients improved amongst those receiving extension exercises. Significant reduction of pain and increase of spinal flexion occurred with each treatment and the periods taken to resume work or sport were similar in each group. Neither exercise regime appeared to have a major influence on recovery. Isometric flexion exercises did not seem to be more beneficial for those with a prominent lumbar lordosis."} {"id": "PMID:160073", "title": "Out-patient physiotherapy: patterns of provision.", "content": "A total of 1014 physiotherapy out-patients and their therapists were interviewed at 10 hospitals in Oxfordshire and Devonshire, including a District General Hospital, a Geriatric, and a sample of associated Community Hospitals in each of the two regions. Over 70% of these patients were suffering from long-term disabilities. The proportion of this type of patient varied between the hospital types, and this variation was similar in the two regions. The overall frequencies with which the different physiotherapy treatments were employed were, for the most part, similar in all departments regardless of hospital type or regions involved. Exercises and heat were the predominant treatments everywhere. The standard frequency of attendance was twice or three times a week. One third of the patients used hospital transport; most patients attended a hospital reasonably close to their homes.", "contents": "Out-patient physiotherapy: patterns of provision. A total of 1014 physiotherapy out-patients and their therapists were interviewed at 10 hospitals in Oxfordshire and Devonshire, including a District General Hospital, a Geriatric, and a sample of associated Community Hospitals in each of the two regions. Over 70% of these patients were suffering from long-term disabilities. The proportion of this type of patient varied between the hospital types, and this variation was similar in the two regions. The overall frequencies with which the different physiotherapy treatments were employed were, for the most part, similar in all departments regardless of hospital type or regions involved. Exercises and heat were the predominant treatments everywhere. The standard frequency of attendance was twice or three times a week. One third of the patients used hospital transport; most patients attended a hospital reasonably close to their homes."} {"id": "PMID:160077", "title": "Muscle biopsy in hypotonic schizophrenic children: a preliminary report.", "content": "Two hypotonic boys, aged 7 years, 3 months and 7 yers, 7 months, who possessed sufficient speech to demonstrate a severe thought disorder and who differed markedly in their activity levels, were subjected to a biopsy of the quadriceps muscle. The biopsies revealed atrophy of type 2 muscle fibers, as well as variability in the size of these fibers. The findings could be compatible with a denervation phenomenon.", "contents": "Muscle biopsy in hypotonic schizophrenic children: a preliminary report. Two hypotonic boys, aged 7 years, 3 months and 7 yers, 7 months, who possessed sufficient speech to demonstrate a severe thought disorder and who differed markedly in their activity levels, were subjected to a biopsy of the quadriceps muscle. The biopsies revealed atrophy of type 2 muscle fibers, as well as variability in the size of these fibers. The findings could be compatible with a denervation phenomenon."} {"id": "PMID:160078", "title": "Mini-laparotomy for bilateral tubal ligation in lithotomy position.", "content": "Two hundred consecutive cases of mini-laparotomy for nonpuerperal bilateral tubal ligation done by a single gynecologist with the patient in lithotomy position are presented here. Technical aspects of the procedure, some innovative and some old, are presented in an effort to demonstrate a simple, low-risk alternative to laparoscopic sterilization.", "contents": "Mini-laparotomy for bilateral tubal ligation in lithotomy position. Two hundred consecutive cases of mini-laparotomy for nonpuerperal bilateral tubal ligation done by a single gynecologist with the patient in lithotomy position are presented here. Technical aspects of the procedure, some innovative and some old, are presented in an effort to demonstrate a simple, low-risk alternative to laparoscopic sterilization."} {"id": "PMID:160083", "title": "Adult scoliosis and back pain.", "content": "From available long-term follow-up studies of untreated scoliosis, there seems to be minimal risk of disabling back pain in adult patients who have lumbar curves. A review of all Swedish patients who in 1971 received disability pension because of scoliosis showed very few who had lumbar curves, significantly fewer and with curves of lesser degrees than patients who had thoracolumbar and thoracic curves. Those exhibiting lumbar curves were mostly 60 years of age or older and had curves around 25 degrees only, of the type that can arise as a result of osteoporosis and disc degeneration. Whether severe low-back pain occurs more often in adults who have lumbar curves than in those whose spines are straight is open to question, since calculations presented show approximately the same incidence of surgery performed for back pain in scoliotic patients and in those whose spines are straight. Because scoliosis surgery in the adult carries a high risk and long-term efficacy is unproved, all types of conservative measures must be tried before discussing an operation. Prophylactic surgery to prevent future back pain in young patients who have lumbar curves is not justified.", "contents": "Adult scoliosis and back pain. From available long-term follow-up studies of untreated scoliosis, there seems to be minimal risk of disabling back pain in adult patients who have lumbar curves. A review of all Swedish patients who in 1971 received disability pension because of scoliosis showed very few who had lumbar curves, significantly fewer and with curves of lesser degrees than patients who had thoracolumbar and thoracic curves. Those exhibiting lumbar curves were mostly 60 years of age or older and had curves around 25 degrees only, of the type that can arise as a result of osteoporosis and disc degeneration. Whether severe low-back pain occurs more often in adults who have lumbar curves than in those whose spines are straight is open to question, since calculations presented show approximately the same incidence of surgery performed for back pain in scoliotic patients and in those whose spines are straight. Because scoliosis surgery in the adult carries a high risk and long-term efficacy is unproved, all types of conservative measures must be tried before discussing an operation. Prophylactic surgery to prevent future back pain in young patients who have lumbar curves is not justified."} {"id": "PMID:160088", "title": "Huntington's chorea in a black family: a report of 2 cases.", "content": "Two cases of Huntington's chorea occurring in a Black family are presented. One patient had, in addition, an arteriovenous anomaly of the cerebral circulation. The genealogy of the family is described and the probability of mixed descent is noted. The impression gained from the literature that Huntington's chorea rarely occurs in Blacks is strengthened.", "contents": "Huntington's chorea in a black family: a report of 2 cases. Two cases of Huntington's chorea occurring in a Black family are presented. One patient had, in addition, an arteriovenous anomaly of the cerebral circulation. The genealogy of the family is described and the probability of mixed descent is noted. The impression gained from the literature that Huntington's chorea rarely occurs in Blacks is strengthened."} {"id": "PMID:160084", "title": "Decision making in adult scoliosis.", "content": "This report analyzes a series of 350 adult patients whose spinal deformity was treated surgically. Indications included pain, curve progression, cosmesis, structural disabilities, neurologic complications, cardiorespiratory problems, and failed previous surgery. Discography was helpful in assessing complex pain problems, and its use led to improved results of surgery because of more comprehensive preoperative definition of the problem. Pain relief occurred in 70% of patients. Traction, either the halo-femoral or the halo-pelvic type, was used in 62 patients. Complex surgery, including anterior and posterior approaches, is required in curves of large magnitude, especially when curves are rigid. Overall curve correction in this series was 40%.", "contents": "Decision making in adult scoliosis. This report analyzes a series of 350 adult patients whose spinal deformity was treated surgically. Indications included pain, curve progression, cosmesis, structural disabilities, neurologic complications, cardiorespiratory problems, and failed previous surgery. Discography was helpful in assessing complex pain problems, and its use led to improved results of surgery because of more comprehensive preoperative definition of the problem. Pain relief occurred in 70% of patients. Traction, either the halo-femoral or the halo-pelvic type, was used in 62 patients. Complex surgery, including anterior and posterior approaches, is required in curves of large magnitude, especially when curves are rigid. Overall curve correction in this series was 40%."} {"id": "PMID:160085", "title": "Adult lumbar scoliosis.", "content": "This report details the expierience with adult lumbar scoliosis among patients at a scoliosis center. Some curves are shown to progress in the adult, while others appear de novo. Pain arising in adult scoliosis may reflect root compression or segmental degeneration. Once pain arises in an adult lumbar curve, it is likely to be progressive and often requires surgical treatment.", "contents": "Adult lumbar scoliosis. This report details the expierience with adult lumbar scoliosis among patients at a scoliosis center. Some curves are shown to progress in the adult, while others appear de novo. Pain arising in adult scoliosis may reflect root compression or segmental degeneration. Once pain arises in an adult lumbar curve, it is likely to be progressive and often requires surgical treatment."} {"id": "PMID:160086", "title": "The management of nerve root entrapment syndromes associated with the collapsing scoliosis of idiopathic lumbar and thoracolumbar curves.", "content": "From 1969 through 1978, 30 adults presented with painful idiopathic scoliosis and associated radicular symptoms. Fifteen had major thoracolumbar curves and 15 had major lumbar curves. Ten (33%) had physical findings of the nerve root entrapment, 4 having two roots entrapped. Root entrapments in the sciatic distribution were most common and arose on the side opposite the major curve, coming from the concavity of compensatory lumbosacral curves (7 of 9 patients). Root entrapment in a femoral nerve distribution came from the concavity of the major curve (1 patient). Whether in a major or compensatory curve, entrapments usually arise in the concavity (8 of 10 patients). Mechanisms of root entrapment vary, but foraminal compression and pedicular kinking were most common. When major deforming curves are corrected fairly completely, most nerve root entrapments are relieved; sciatic entrapments are decompressed by spontaneous straightening of the lumbosacral curve. Dwyer instrumentation and fusion has been the most effective method of surgical management in carefully selected cases.", "contents": "The management of nerve root entrapment syndromes associated with the collapsing scoliosis of idiopathic lumbar and thoracolumbar curves. From 1969 through 1978, 30 adults presented with painful idiopathic scoliosis and associated radicular symptoms. Fifteen had major thoracolumbar curves and 15 had major lumbar curves. Ten (33%) had physical findings of the nerve root entrapment, 4 having two roots entrapped. Root entrapments in the sciatic distribution were most common and arose on the side opposite the major curve, coming from the concavity of compensatory lumbosacral curves (7 of 9 patients). Root entrapment in a femoral nerve distribution came from the concavity of the major curve (1 patient). Whether in a major or compensatory curve, entrapments usually arise in the concavity (8 of 10 patients). Mechanisms of root entrapment vary, but foraminal compression and pedicular kinking were most common. When major deforming curves are corrected fairly completely, most nerve root entrapments are relieved; sciatic entrapments are decompressed by spontaneous straightening of the lumbosacral curve. Dwyer instrumentation and fusion has been the most effective method of surgical management in carefully selected cases."} {"id": "PMID:160090", "title": "Pulsed Doppler angiography in lower limb arterial ischemia.", "content": "A 30-channel pulsed Doppler vessel imaging system (MAVIS, GEC Medical, Middlesex, England), was used to obtain images and maximal Doppler velocity time waveforms in the diagnosis of stenosis of the origin of the profunda femoris artery (PFA) and in the detection of structural changes within Dacron arterial grafts. In PFA scans of 33 limbs in 22 patients (mean age, 52 years), PFA stenosis of more than 50% at operation was invariably associated with a damping factor of the maximal Doppler velocity-time waveform of greater than 1.5 (eight limbs). In 12 limbs with a normal PFA at operation, the damping factor was always less than 1.4, and in 13 limbs of normal patients without arterial disease, the damping factor was always less than 1.34. In studies of 10 mm arterial grafts, the internal diameter of 14 iliopopliteal grafts scanned just above the popliteal anastomosis was strikingly reduced as compared with the femoral anastomosis of 14 aortoiliofemoral grafts and seven axillobifemoral grafts. These preliminary results suggest that MAVIS studies can be used noninvasively to detect PFA stenosis and to identify luminal narrowing of iliopopliteal grafts.", "contents": "Pulsed Doppler angiography in lower limb arterial ischemia. A 30-channel pulsed Doppler vessel imaging system (MAVIS, GEC Medical, Middlesex, England), was used to obtain images and maximal Doppler velocity time waveforms in the diagnosis of stenosis of the origin of the profunda femoris artery (PFA) and in the detection of structural changes within Dacron arterial grafts. In PFA scans of 33 limbs in 22 patients (mean age, 52 years), PFA stenosis of more than 50% at operation was invariably associated with a damping factor of the maximal Doppler velocity-time waveform of greater than 1.5 (eight limbs). In 12 limbs with a normal PFA at operation, the damping factor was always less than 1.4, and in 13 limbs of normal patients without arterial disease, the damping factor was always less than 1.34. In studies of 10 mm arterial grafts, the internal diameter of 14 iliopopliteal grafts scanned just above the popliteal anastomosis was strikingly reduced as compared with the femoral anastomosis of 14 aortoiliofemoral grafts and seven axillobifemoral grafts. These preliminary results suggest that MAVIS studies can be used noninvasively to detect PFA stenosis and to identify luminal narrowing of iliopopliteal grafts."} {"id": "PMID:160092", "title": "Rapidly fatal pulmonary fibrosis: the accelerated variant of interstitial pneumonitis.", "content": "We sought to explore immunological factors in patients who died with rapidly fatal fibrosing lung diseases (Hamman-Rich syndrome). A retrospective review of cases of interstitial lung disease showed 12 recent deaths from Hamman-Rich syndrome. The mean age was 62, men outnumbering women 3 : 1. Five patients had proved collagen vascular disease (rheumatoid arthritis three, lupus two). Four others had a history of allergic disorders, syphilis, chronic eosinophilia, or hypersensitivity reactions. One patient showed disappearance of immunofluorescence as fibrosis advanced, which has not previously been reported. The study suggests a possible aetiological link between disorders of immunity and Hamman-Rich syndrome. The evidence also supports the notion that Hamman-Rich syndrome is an accelerated variant of the more indolent interstitial pneumonias.", "contents": "Rapidly fatal pulmonary fibrosis: the accelerated variant of interstitial pneumonitis. We sought to explore immunological factors in patients who died with rapidly fatal fibrosing lung diseases (Hamman-Rich syndrome). A retrospective review of cases of interstitial lung disease showed 12 recent deaths from Hamman-Rich syndrome. The mean age was 62, men outnumbering women 3 : 1. Five patients had proved collagen vascular disease (rheumatoid arthritis three, lupus two). Four others had a history of allergic disorders, syphilis, chronic eosinophilia, or hypersensitivity reactions. One patient showed disappearance of immunofluorescence as fibrosis advanced, which has not previously been reported. The study suggests a possible aetiological link between disorders of immunity and Hamman-Rich syndrome. The evidence also supports the notion that Hamman-Rich syndrome is an accelerated variant of the more indolent interstitial pneumonias."} {"id": "PMID:160100", "title": "Laparoscopy combined with peritoneal cytology in staging and restaging ovarian carcinoma.", "content": "The merits of laparoscopy, with inspection of the diaphragmatic leaves, and of peritoneal cytology (free fluid or washing) in staging and restaging were studied in 153 patients with ovarian carcinoma. Of 153 patients examined, 83 were new cases, 34 were restaging in patients without clinical and/or radiological signs of disease, and 36 in patients with evident disease. The conversion rate for diaphragmatic metastases alone was 6%. Information about the spread of disease (diaphragmatic metastases) was obtained in 33 new cases (39.7%). In pretreated patients, laparoscopy was positive in 4 of 34 NED restaging and in 24 of 36 ED restaging. The conversion rate for peritoneal cytology was 6.6%, but information about the cellular intraperitoneal spread of the disease was obtained in 31 new cases (37.8%). In pretreated patients, peritoneal cytology was positive in 4 of 34 NED restaging and in 13 of 36 ED restaging.", "contents": "Laparoscopy combined with peritoneal cytology in staging and restaging ovarian carcinoma. The merits of laparoscopy, with inspection of the diaphragmatic leaves, and of peritoneal cytology (free fluid or washing) in staging and restaging were studied in 153 patients with ovarian carcinoma. Of 153 patients examined, 83 were new cases, 34 were restaging in patients without clinical and/or radiological signs of disease, and 36 in patients with evident disease. The conversion rate for diaphragmatic metastases alone was 6%. Information about the spread of disease (diaphragmatic metastases) was obtained in 33 new cases (39.7%). In pretreated patients, laparoscopy was positive in 4 of 34 NED restaging and in 24 of 36 ED restaging. The conversion rate for peritoneal cytology was 6.6%, but information about the cellular intraperitoneal spread of the disease was obtained in 31 new cases (37.8%). In pretreated patients, peritoneal cytology was positive in 4 of 34 NED restaging and in 13 of 36 ED restaging."} {"id": "PMID:160102", "title": "[Changes in properties of actomyosin in the process of ontogenesis].", "content": "The paper deals with some data on nonidentical heat-resistance of actomyosin of the skeletal muscles and myocardium of the calf foetus and adult animals. It is shown that in the process of uterine development the ATPase activity increases and at alkaline pH the Ca2+-activated ATPase of natural actomyosin of the cattle skeletal muscles and myocardium is activated. Heat-resistance of ATPase of the skeletal muscles and myocardium decreases with age, the myocardium actimyosin ATPase being more stable to heating. These denatured changes are found to be of a reversible character.", "contents": "[Changes in properties of actomyosin in the process of ontogenesis]. The paper deals with some data on nonidentical heat-resistance of actomyosin of the skeletal muscles and myocardium of the calf foetus and adult animals. It is shown that in the process of uterine development the ATPase activity increases and at alkaline pH the Ca2+-activated ATPase of natural actomyosin of the cattle skeletal muscles and myocardium is activated. Heat-resistance of ATPase of the skeletal muscles and myocardium decreases with age, the myocardium actimyosin ATPase being more stable to heating. These denatured changes are found to be of a reversible character."} {"id": "PMID:160117", "title": "Detection of HBsAg containing cells in liver biopsies by different stains and classification of positively reacting ground-glass hepatocytes.", "content": "The diagnostic significance of orcein, aldehydthionine, and chromotrope anilinblue stains for the demonstration of HBsAg containing hepatocytes was investigated in 602 unselected liver biopsies. Five types of specifically stained ground-glass hepatocytes (GGH) were distinguished: Type I showed a positive staining reaction of the cytoplasmic periphery (marginal GGH), type II a diffuse staining of the total cytoplasm (diffuse GGH). Type III contained round or oval globular positive cytoplasmic masses (globular GGH). Type IV showed only very small round, drop-like or sickle-shaped positive structures (spotty GGH). The GGH with fatty changes were designated as type V. In all carriers and patients with minimal hepatitis GGH, mostly type I and II, appeared in extensive clusters within the lobules. In chronic persistent hepatitis, there were moderately numerous, partly grouped, partly disseminated ground-glass hepatocytes of type II and III. In chronic active hepatitis there were only a few GGH of type IV. In acute viral hepatitis, there were no typical GGH, however, positively stained phagocytes were seen. The intracellular antigen localization and the intralobular distribution of GGH are considered to be the result of an immune reaction. Single so-called 'metabolic' GGH sometimes showed similar pictures. However, they could usually be distinguished from virus containing GGH because of their granular cytoplasmic structure and a lower staining intensity in the applied stains. Among the three stains the orcein stain yielded the best results. In some cases with HBsAg-positive chronic active hepatitis virus infection could not be proved by means of staining.", "contents": "Detection of HBsAg containing cells in liver biopsies by different stains and classification of positively reacting ground-glass hepatocytes. The diagnostic significance of orcein, aldehydthionine, and chromotrope anilinblue stains for the demonstration of HBsAg containing hepatocytes was investigated in 602 unselected liver biopsies. Five types of specifically stained ground-glass hepatocytes (GGH) were distinguished: Type I showed a positive staining reaction of the cytoplasmic periphery (marginal GGH), type II a diffuse staining of the total cytoplasm (diffuse GGH). Type III contained round or oval globular positive cytoplasmic masses (globular GGH). Type IV showed only very small round, drop-like or sickle-shaped positive structures (spotty GGH). The GGH with fatty changes were designated as type V. In all carriers and patients with minimal hepatitis GGH, mostly type I and II, appeared in extensive clusters within the lobules. In chronic persistent hepatitis, there were moderately numerous, partly grouped, partly disseminated ground-glass hepatocytes of type II and III. In chronic active hepatitis there were only a few GGH of type IV. In acute viral hepatitis, there were no typical GGH, however, positively stained phagocytes were seen. The intracellular antigen localization and the intralobular distribution of GGH are considered to be the result of an immune reaction. Single so-called 'metabolic' GGH sometimes showed similar pictures. However, they could usually be distinguished from virus containing GGH because of their granular cytoplasmic structure and a lower staining intensity in the applied stains. Among the three stains the orcein stain yielded the best results. In some cases with HBsAg-positive chronic active hepatitis virus infection could not be proved by means of staining."} {"id": "PMID:160118", "title": "Carcinogenicity of 1,2-dimethylhydrazine dihydrochloride in BALB/c mice. Influence of the route of administration and dosage.", "content": "The carcinogenicity of 1,2-dimethylhydrazine dihydrochloride (DMH) by oral, intragastric and subcutaneous administration was examined in 339 BALB/c mice. Subcutaneous injection of DMH induced intestinal tumors in the lower colon of all mice. After oral administration it induced a high incidence of vascular tumors in the liver and soft tissues, but colon tumors were found in only 2 mice when given at a high dosage. On intragastric administration, it induced a fairly high incidence both of colon and vascular tumors. The sites and incidences of vascular tumors and squamous cell carcinomas of the perianal glands were also described.", "contents": "Carcinogenicity of 1,2-dimethylhydrazine dihydrochloride in BALB/c mice. Influence of the route of administration and dosage. The carcinogenicity of 1,2-dimethylhydrazine dihydrochloride (DMH) by oral, intragastric and subcutaneous administration was examined in 339 BALB/c mice. Subcutaneous injection of DMH induced intestinal tumors in the lower colon of all mice. After oral administration it induced a high incidence of vascular tumors in the liver and soft tissues, but colon tumors were found in only 2 mice when given at a high dosage. On intragastric administration, it induced a fairly high incidence both of colon and vascular tumors. The sites and incidences of vascular tumors and squamous cell carcinomas of the perianal glands were also described."} {"id": "PMID:160120", "title": "Possible evidence for secondary degeneration of central nervous system in the pathogenesis of anencephaly and brain dysraphia. A study in young human fetuses.", "content": "In an attempt to help elucidate pathogenetically those human cases exemplifying secondary degeneration of the neural tube causing brain dysraphia, macroscopic and histologic observations of two young human fetuses are described. A nine-week-old anencephalic fetus exhibited an absence of spinal cord (amyelia) with retention of neural crest derivatives (dorsal root ganglion cells and thusir processes, and sympathetic ganglia) implying the presence of a neural tube in early gestation. The second, ten-week-old exencephalic case exhibited restricted brain hemorrhage and necrosis of the telencephalon and brain stem amongst otherwise normal brain and spinal cord tissue. These two young fetal cases may represent examples of a previously normal neural tube which has undergone degeneration at a stage where neural crest has already undergone differentiation, and thus distinguishes them from cases of complete dysraphism which probably results from primary degeneration during neurulation.", "contents": "Possible evidence for secondary degeneration of central nervous system in the pathogenesis of anencephaly and brain dysraphia. A study in young human fetuses. In an attempt to help elucidate pathogenetically those human cases exemplifying secondary degeneration of the neural tube causing brain dysraphia, macroscopic and histologic observations of two young human fetuses are described. A nine-week-old anencephalic fetus exhibited an absence of spinal cord (amyelia) with retention of neural crest derivatives (dorsal root ganglion cells and thusir processes, and sympathetic ganglia) implying the presence of a neural tube in early gestation. The second, ten-week-old exencephalic case exhibited restricted brain hemorrhage and necrosis of the telencephalon and brain stem amongst otherwise normal brain and spinal cord tissue. These two young fetal cases may represent examples of a previously normal neural tube which has undergone degeneration at a stage where neural crest has already undergone differentiation, and thus distinguishes them from cases of complete dysraphism which probably results from primary degeneration during neurulation."} {"id": "PMID:160121", "title": "Changes in the small biliary passages in the hepatic localization of Hodgkin's disease.", "content": "The authors have investigated the behaviour of the small biliary passages in the liver biopsies of six patients suffering from untreated Hodgkin's disease with hepatic localization. No obstruction of the major bile ducts was demonstrated in any patient. Three of the patients were anicteric, while the three others presented with jaundice. In the first three cases typical Hodgkin's granulation tissue appears to be limited to portal tracts and collagen reaction is virtually absent. The three cases with cholestasis showed granulomatous tissue associated with heavy connective tissue rearrangement invading and dissociating the lobular structure. They also show a conspicuous bile-duct proliferation, which is not observed in the three anicteric patients. In these latter cases, however, the small bile ducts running within or near the granulomatous tissue present various morphologic changes, including basal membrane thickening, dilation or constriction of the lumen and alterations of the biliary epithelial lining. Complete disappearance of the bile duct may occur.", "contents": "Changes in the small biliary passages in the hepatic localization of Hodgkin's disease. The authors have investigated the behaviour of the small biliary passages in the liver biopsies of six patients suffering from untreated Hodgkin's disease with hepatic localization. No obstruction of the major bile ducts was demonstrated in any patient. Three of the patients were anicteric, while the three others presented with jaundice. In the first three cases typical Hodgkin's granulation tissue appears to be limited to portal tracts and collagen reaction is virtually absent. The three cases with cholestasis showed granulomatous tissue associated with heavy connective tissue rearrangement invading and dissociating the lobular structure. They also show a conspicuous bile-duct proliferation, which is not observed in the three anicteric patients. In these latter cases, however, the small bile ducts running within or near the granulomatous tissue present various morphologic changes, including basal membrane thickening, dilation or constriction of the lumen and alterations of the biliary epithelial lining. Complete disappearance of the bile duct may occur."} {"id": "PMID:160123", "title": "Dissecting aneurysm of cerebral arteries in childhood and adolescence. Case report and literature review of 20 cases.", "content": "A nine year old girl died with a massive infarct of the right cerebral hemisphere causing transtentorial and foramen magnum herniation. The infarction was secondary to an idiopathic dissecting aneurysm. The case is unusual in that the supraclinoid segment of the right internal carotid artery, the anterior cerebral artery, and the middle cerebral artery and its three branches were embedded and sectioned longitudinally. The dissection commenced in the supraclinoid segment of the right internal carotid artery, extended into the middle and anterior cerebral arteries, and was accompanied by thrombosis of the false lumen. A literature review of 20 pediatric cases indicates the malignant natural course of the disease (76% mortality in the first two months), and emphasizes the characteristic angiographic \"string sign\". The diagnosis of cerebral arterial dissection during life depends on angiography and a high index of suspicion.", "contents": "Dissecting aneurysm of cerebral arteries in childhood and adolescence. Case report and literature review of 20 cases. A nine year old girl died with a massive infarct of the right cerebral hemisphere causing transtentorial and foramen magnum herniation. The infarction was secondary to an idiopathic dissecting aneurysm. The case is unusual in that the supraclinoid segment of the right internal carotid artery, the anterior cerebral artery, and the middle cerebral artery and its three branches were embedded and sectioned longitudinally. The dissection commenced in the supraclinoid segment of the right internal carotid artery, extended into the middle and anterior cerebral arteries, and was accompanied by thrombosis of the false lumen. A literature review of 20 pediatric cases indicates the malignant natural course of the disease (76% mortality in the first two months), and emphasizes the characteristic angiographic \"string sign\". The diagnosis of cerebral arterial dissection during life depends on angiography and a high index of suspicion."} {"id": "PMID:160124", "title": "Fine structural evidence of increased endothelial permeability in chronic lathyrism.", "content": "The endothelium of the thoracic aorta of Wistar rats intoxicated with Beta-Aminopropionitrile (BAPN) for 9 weeks was studied. The animals were sacrificed at intervals, from the first to the 9th week of the treatment and 1, 2 and 3 months after the end of the treatment. Changes in the endothelial cells were studied by electron microscopy after staining with uranyl acetate and lead citrate, after impregnation with lanthanum. BAPN increased endothelial permeability, pinocytosis was more active in treated rats than controls, the intercellular junctions widened and cytoplasmic lesions with cell necrosis occurred. These intimal changes were comparable to those observed in man during ageing and in arteriosclerosis.", "contents": "Fine structural evidence of increased endothelial permeability in chronic lathyrism. The endothelium of the thoracic aorta of Wistar rats intoxicated with Beta-Aminopropionitrile (BAPN) for 9 weeks was studied. The animals were sacrificed at intervals, from the first to the 9th week of the treatment and 1, 2 and 3 months after the end of the treatment. Changes in the endothelial cells were studied by electron microscopy after staining with uranyl acetate and lead citrate, after impregnation with lanthanum. BAPN increased endothelial permeability, pinocytosis was more active in treated rats than controls, the intercellular junctions widened and cytoplasmic lesions with cell necrosis occurred. These intimal changes were comparable to those observed in man during ageing and in arteriosclerosis."} {"id": "PMID:160125", "title": "The trabecular meshwork of a non-glaucomatous eye with the exfoliation syndrome. Electronmicroscopic study.", "content": "The trabecular meshwork of a non-glaucomatous eye with the exfoliation syndrome was investigated. The exfoliation material was found mainly in massive deposits in the subendothelial region of the outer and inner wall of Schlemm's canal, in the cribriform area and the uveal meshwork. The other alterations of the trabeculum corneosclerale corresponded to the age of the patient. The concept that the accumulation of exfoliation material is an important pathogenetic factor in the development of glaucoma was not confirmed by this study.", "contents": "The trabecular meshwork of a non-glaucomatous eye with the exfoliation syndrome. Electronmicroscopic study. The trabecular meshwork of a non-glaucomatous eye with the exfoliation syndrome was investigated. The exfoliation material was found mainly in massive deposits in the subendothelial region of the outer and inner wall of Schlemm's canal, in the cribriform area and the uveal meshwork. The other alterations of the trabeculum corneosclerale corresponded to the age of the patient. The concept that the accumulation of exfoliation material is an important pathogenetic factor in the development of glaucoma was not confirmed by this study."} {"id": "PMID:160126", "title": "Large basophilic cells in the bone marrow in iron deficiency anemia.", "content": "Many large cells with a strongly basophilic cytoplasm and large nuclei with a delicate chromatin pattern and large nucleoli were studied in 1 mu sections of core biopsies in 8 patients with iron deficiency anemia and in 5 patients with pernicious anemia. In 2 normal controls these cells were rare. Possible features of granulocytic differentiation were assessed with the Giemsa stain and with the naphtol-ASD-chloroacetate esterase reaction which is indicative of early granule formation: the large cells were constantly negative. In thin sections the morphological appearances of the large basophilic cells are rather similar in such different haematological disorders as pernicious anemia or iron deficiency anemia. A clear difference can be demonstrated by karyometry, which shows that the large basophilic cells in pernicious anemia are significantly larger than those in iron deficiency anemia or in the normal control.", "contents": "Large basophilic cells in the bone marrow in iron deficiency anemia. Many large cells with a strongly basophilic cytoplasm and large nuclei with a delicate chromatin pattern and large nucleoli were studied in 1 mu sections of core biopsies in 8 patients with iron deficiency anemia and in 5 patients with pernicious anemia. In 2 normal controls these cells were rare. Possible features of granulocytic differentiation were assessed with the Giemsa stain and with the naphtol-ASD-chloroacetate esterase reaction which is indicative of early granule formation: the large cells were constantly negative. In thin sections the morphological appearances of the large basophilic cells are rather similar in such different haematological disorders as pernicious anemia or iron deficiency anemia. A clear difference can be demonstrated by karyometry, which shows that the large basophilic cells in pernicious anemia are significantly larger than those in iron deficiency anemia or in the normal control."} {"id": "PMID:160131", "title": "[Posthypoxic changes in the metabolism of the developing brain].", "content": "Effect of intranatal hypoxia on content of adenylic nucleotides, glycogen, lactic acid as well as on activity of ATP-ases and concentration of free amino acids was studied in rat brain tissue at various periods of postnatal development (I day-5 months). Acute hypoxia was accompanied by a decrease in content of adenylic nucleotides and glycogen, by an increase in concentration of lactic acid and by a decrease in activity of ATP-ases. During the subsequent periods, in brain tissue of animals, subjected to hypoxia, posthypoxic activation of energy metabolism was found, which depended apparently on the decreased intensity of plastic processes during the phase of active growth and of neurone differentiation. Content of the essential amino acids, actively participating in protein synthesis, was increased but concentration of nonessential amino acids was decreased at this step. The subsequent decrease in content of macroergic compounds, increase in concentration of lactic acid and inorganic phosphate as well as the decrease in activity of ATP-ases were observed in 1.5-2 months old experimental animals. The biochemical and mophological data suggest that intranatal hypoxia is responsible for irreversible impairments in developing brain.", "contents": "[Posthypoxic changes in the metabolism of the developing brain]. Effect of intranatal hypoxia on content of adenylic nucleotides, glycogen, lactic acid as well as on activity of ATP-ases and concentration of free amino acids was studied in rat brain tissue at various periods of postnatal development (I day-5 months). Acute hypoxia was accompanied by a decrease in content of adenylic nucleotides and glycogen, by an increase in concentration of lactic acid and by a decrease in activity of ATP-ases. During the subsequent periods, in brain tissue of animals, subjected to hypoxia, posthypoxic activation of energy metabolism was found, which depended apparently on the decreased intensity of plastic processes during the phase of active growth and of neurone differentiation. Content of the essential amino acids, actively participating in protein synthesis, was increased but concentration of nonessential amino acids was decreased at this step. The subsequent decrease in content of macroergic compounds, increase in concentration of lactic acid and inorganic phosphate as well as the decrease in activity of ATP-ases were observed in 1.5-2 months old experimental animals. The biochemical and mophological data suggest that intranatal hypoxia is responsible for irreversible impairments in developing brain."} {"id": "PMID:160132", "title": "[Participation of Mg2+ and Ca2+ ions and the corresponding ATPases in the mechanism of the presynaptic action of amisyl and arecoline].", "content": "Amisyle and arecoline were found to be antagonistic drugs in the effect on content of Mg2+ and Ca2+ and on activity of corresponding ATPases in synaptosomes isolated from rat brain. Amisyle promoted the incorporation of 45Ca into synaptosomes but arecoline inhibited the reaction. The appear to be responsible for liberation and maintaining of neurotransmitters in presinaptic stores.", "contents": "[Participation of Mg2+ and Ca2+ ions and the corresponding ATPases in the mechanism of the presynaptic action of amisyl and arecoline]. Amisyle and arecoline were found to be antagonistic drugs in the effect on content of Mg2+ and Ca2+ and on activity of corresponding ATPases in synaptosomes isolated from rat brain. Amisyle promoted the incorporation of 45Ca into synaptosomes but arecoline inhibited the reaction. The appear to be responsible for liberation and maintaining of neurotransmitters in presinaptic stores."} {"id": "PMID:160139", "title": "Conservatorship: an involuntary legal status for 'gravely disabled' mentally disordered persons.", "content": "Since 1969 in California, conservatorship has been the only form of civil, longterm involuntary psychiatric legal process. It does not require hospital-based treatment. This paper reports a preliminary study of this process through a retrospective analysis of conservatorship records in Sacramento County, California, from 1969 through 1976. There is a steady overall increase in the incidence of conservatorships each year. A dramatic decrease in state hospital admissions preceded this increase. Referrals were predominantly (69 percent) from the private sector. Once the first legal step was taken 87 percent of the patients completed the process and were placed on full conservatorship. Median age was 50; 52 percent were male and 90 percent were white. The relative proportion of single persons was high (45 percent). Diagnoses of schizophrenia and organic brain syndrome accounted for 86 percent of conservatees. About half (52 percent) terminate conservatorship after one year. No data were found which could be related to the character of treatment of conservatees. Future research in this area is urgently needed.", "contents": "Conservatorship: an involuntary legal status for 'gravely disabled' mentally disordered persons. Since 1969 in California, conservatorship has been the only form of civil, longterm involuntary psychiatric legal process. It does not require hospital-based treatment. This paper reports a preliminary study of this process through a retrospective analysis of conservatorship records in Sacramento County, California, from 1969 through 1976. There is a steady overall increase in the incidence of conservatorships each year. A dramatic decrease in state hospital admissions preceded this increase. Referrals were predominantly (69 percent) from the private sector. Once the first legal step was taken 87 percent of the patients completed the process and were placed on full conservatorship. Median age was 50; 52 percent were male and 90 percent were white. The relative proportion of single persons was high (45 percent). Diagnoses of schizophrenia and organic brain syndrome accounted for 86 percent of conservatees. About half (52 percent) terminate conservatorship after one year. No data were found which could be related to the character of treatment of conservatees. Future research in this area is urgently needed."} {"id": "PMID:160141", "title": "[Ocular signs in cases of down's syndrome (author's transl)].", "content": "420 mongoloid children aged between one month and 14 years were examined in a special ophthalmology department for disabled children employing biomicroscopy, retinoscopy under atropine and, if possible, visual acuity testing. Epicanthal folds were present in 46%, mongoloid slanting of the lids in 72% of cases. A decrease in binocular vision was present in 40% of the children. Brushfield's spots were encountered in 86% of the patients in a circular arrangement, whilst in 7% only the temporal half of the iris was involved. Lens changes of a variable degree were present in altogether 55% of cases and an increase in the number of retinal vessels, as well as their radial arrangement, as described by Williams, were documented in 46% of the cases. A comparison of the incidence and degree of refractive anomalies in mongoloid and normal children was undertaken. The present findings are discussed and compared with the results of other investigators.", "contents": "[Ocular signs in cases of down's syndrome (author's transl)]. 420 mongoloid children aged between one month and 14 years were examined in a special ophthalmology department for disabled children employing biomicroscopy, retinoscopy under atropine and, if possible, visual acuity testing. Epicanthal folds were present in 46%, mongoloid slanting of the lids in 72% of cases. A decrease in binocular vision was present in 40% of the children. Brushfield's spots were encountered in 86% of the patients in a circular arrangement, whilst in 7% only the temporal half of the iris was involved. Lens changes of a variable degree were present in altogether 55% of cases and an increase in the number of retinal vessels, as well as their radial arrangement, as described by Williams, were documented in 46% of the cases. A comparison of the incidence and degree of refractive anomalies in mongoloid and normal children was undertaken. The present findings are discussed and compared with the results of other investigators."} {"id": "PMID:160142", "title": "[Clinical experience with levamisole treatment of patients with systemic lupus erythematosus (author's transl)].", "content": "Levamisole treatment was started in 8 patients with inactive SLE. Four patients, who have now been followed up for over 12 months, have not shown clinical deterioration. Three of these patients received concomitant maintenance corticosteroid therapy, the dosage of which could be reduced in each case. A decrease in anti-DNA antibodies was observed in all 4 patients. Levamisole had to be withdrawn in the other 4 patients. One patient developed an exacerbation of her LE skin manifestations after two months, whilst in another patient fever and skin rash (probably drug-induced) were observed after one month. The cooperation of the 2 other patients was not satisfactory and the drug had, thus, to be withdrawn. In conclusion, 4 out of 8 patients with SLE showed a beneficial response to levamisole therapy.", "contents": "[Clinical experience with levamisole treatment of patients with systemic lupus erythematosus (author's transl)]. Levamisole treatment was started in 8 patients with inactive SLE. Four patients, who have now been followed up for over 12 months, have not shown clinical deterioration. Three of these patients received concomitant maintenance corticosteroid therapy, the dosage of which could be reduced in each case. A decrease in anti-DNA antibodies was observed in all 4 patients. Levamisole had to be withdrawn in the other 4 patients. One patient developed an exacerbation of her LE skin manifestations after two months, whilst in another patient fever and skin rash (probably drug-induced) were observed after one month. The cooperation of the 2 other patients was not satisfactory and the drug had, thus, to be withdrawn. In conclusion, 4 out of 8 patients with SLE showed a beneficial response to levamisole therapy."} {"id": "PMID:160145", "title": "[Computer-Cardiotomography (author's transl)].", "content": "Based on our first 200 investigations computed tomography of the heart is demonstrated as a new non-invasive roentgenography on typical examples and compared with the findings of the conventional roentgenogram. With the present technology the following indications for computed tomography of the heart seem to be reasonable: Calculation of size and volume of the cavities of the heart; intracavitary space occupying lesions (tumor, thrombus): demonstration of the thickness of the ventricular wall and ventricular septum and their changes caused by hypertrophy, myocardial infarction or septal defect; demonstration of aortic and ventricular aneurysm; demonstration of pericardial effusion, pericardial tumor, pericardial cyst of lipoma.", "contents": "[Computer-Cardiotomography (author's transl)]. Based on our first 200 investigations computed tomography of the heart is demonstrated as a new non-invasive roentgenography on typical examples and compared with the findings of the conventional roentgenogram. With the present technology the following indications for computed tomography of the heart seem to be reasonable: Calculation of size and volume of the cavities of the heart; intracavitary space occupying lesions (tumor, thrombus): demonstration of the thickness of the ventricular wall and ventricular septum and their changes caused by hypertrophy, myocardial infarction or septal defect; demonstration of aortic and ventricular aneurysm; demonstration of pericardial effusion, pericardial tumor, pericardial cyst of lipoma."} {"id": "PMID:160146", "title": "[Long-term treatment of bradycardia by means of an atropine ester (SCH 1000). Electrophysiological and clinical results].", "content": "Electrophysiological effects of the atropin ester Ipatropiumbromide (SCH 1000) were investigated in 15 patients by His electrocardiography and high frequency atrial stimulation. Heart rate increased by 50% of base line heart rate, PA- and AH-intervals and sinus node recovery time decreased, the HF-interval remained unchanged. Physiological av-block by atrial stimulation occurred at significant higher stimulation frequencies with SCH 1000 than without medication. Additional 15 patients were treated for a longer follow-up period. Increase of resting heart rate averaged 15%. Equivocal effects on heart rate were found with exercise after SCH 1000. Non-cardiac side effects were found in 5 patients.", "contents": "[Long-term treatment of bradycardia by means of an atropine ester (SCH 1000). Electrophysiological and clinical results]. Electrophysiological effects of the atropin ester Ipatropiumbromide (SCH 1000) were investigated in 15 patients by His electrocardiography and high frequency atrial stimulation. Heart rate increased by 50% of base line heart rate, PA- and AH-intervals and sinus node recovery time decreased, the HF-interval remained unchanged. Physiological av-block by atrial stimulation occurred at significant higher stimulation frequencies with SCH 1000 than without medication. Additional 15 patients were treated for a longer follow-up period. Increase of resting heart rate averaged 15%. Equivocal effects on heart rate were found with exercise after SCH 1000. Non-cardiac side effects were found in 5 patients."} {"id": "PMID:160147", "title": "A histochemical study of the neuro-muscular spindles in the tongue of some rodents.", "content": "An investigation was undertaken to study the Neuro-muscular spindles in the tongue (Rattus rattus rufescens and Suncus murinus) by cholinesterase technique, under maintained pH of 5.2, incubation period 20 h., and temperature 38 degrees C (Rattus) and 39 degrees C (Suncus). Neuro-muscular spindles were observed frequently distributed from anterior to posterior of the tongue and took a little darker stain than the ordinary muscle fibres (negatively stained) while the nerve fibres and ganglia took still darker stain. Nerve fibres (myelinated, non-myelinated and tortuous) were seen penetrating and embracing the muscle spindles and most of them ran parallel to the spindles. Ganglia of various shapes (oval, irregular, elongated and rounded) and sizes (large, Rattus and medium and small, Suncus) were AChE-positive. Ganglia small and medium in size, rounded and elongated in shape were arranged in chain-like fashion on the muscle spindles in Suncus (Fig. 9, 10). The blood vessels (artery, vein, and capillary) were recorded either in close association with the muscle spindles or lying parallel to it. In all cases they were closely related and deeply associate either with the nerve fibres of the plexus of the muscle spindles or with the nerve fibres of the neural network of vessel. Perivascular and perimuscular ganglia with pre- and postganglionic nerve fibres were closely related to each other. Nerve endings, dot-like (Rattus) and bulb-like (Suncus) were occasionally recorded. AChE activity was found randomly in the muscle spindles (Fig. 2, 5.) and in the form of dark brown patches in the ordinary muscle fibres.", "contents": "A histochemical study of the neuro-muscular spindles in the tongue of some rodents. An investigation was undertaken to study the Neuro-muscular spindles in the tongue (Rattus rattus rufescens and Suncus murinus) by cholinesterase technique, under maintained pH of 5.2, incubation period 20 h., and temperature 38 degrees C (Rattus) and 39 degrees C (Suncus). Neuro-muscular spindles were observed frequently distributed from anterior to posterior of the tongue and took a little darker stain than the ordinary muscle fibres (negatively stained) while the nerve fibres and ganglia took still darker stain. Nerve fibres (myelinated, non-myelinated and tortuous) were seen penetrating and embracing the muscle spindles and most of them ran parallel to the spindles. Ganglia of various shapes (oval, irregular, elongated and rounded) and sizes (large, Rattus and medium and small, Suncus) were AChE-positive. Ganglia small and medium in size, rounded and elongated in shape were arranged in chain-like fashion on the muscle spindles in Suncus (Fig. 9, 10). The blood vessels (artery, vein, and capillary) were recorded either in close association with the muscle spindles or lying parallel to it. In all cases they were closely related and deeply associate either with the nerve fibres of the plexus of the muscle spindles or with the nerve fibres of the neural network of vessel. Perivascular and perimuscular ganglia with pre- and postganglionic nerve fibres were closely related to each other. Nerve endings, dot-like (Rattus) and bulb-like (Suncus) were occasionally recorded. AChE activity was found randomly in the muscle spindles (Fig. 2, 5.) and in the form of dark brown patches in the ordinary muscle fibres."} {"id": "PMID:160151", "title": "[Experimental studies on the use of direct bonding in dental orthopedics (author's transl)].", "content": "Plastic filling materials of the Noracryl 100 and Evicrol type were used on twenty extracted teeth as adhesives for direct bonding. The two plastic materials did not differ in fatigue and tear-off test results.--The values of tensile strength were many times those of therapeutically effective orthodontic forces. Using replicas and scanning electron micrographs of the enamel surface, it was possible to show that, after bracket removal and polishing, residues of Noracryl are more easily removable than those of Evicrol.--Initial clinical tests allowed these results to be verified.", "contents": "[Experimental studies on the use of direct bonding in dental orthopedics (author's transl)]. Plastic filling materials of the Noracryl 100 and Evicrol type were used on twenty extracted teeth as adhesives for direct bonding. The two plastic materials did not differ in fatigue and tear-off test results.--The values of tensile strength were many times those of therapeutically effective orthodontic forces. Using replicas and scanning electron micrographs of the enamel surface, it was possible to show that, after bracket removal and polishing, residues of Noracryl are more easily removable than those of Evicrol.--Initial clinical tests allowed these results to be verified."} {"id": "PMID:160152", "title": "[First results of experimental animal studies on pervascular effects of indwelling intravasal catheters upon free tissue grafts. First communication (author's transl)].", "content": "This is the first in a series of two papers reporting first results of studies made to set up a basic model of intraarterial perfusions in free tissue grafts. Epidermal tissue grafts were obtained from thirty-two domestic pigs prior to slaughtering and pervascularly perfused for twelve to ninety-six hours. Histological examinations showed that it is possible for tissue necrosis to be arrested as a prerequisite of subsequent in vivo experiments performed with the object of pervascularly supporting the healing-in of tissue grafts.", "contents": "[First results of experimental animal studies on pervascular effects of indwelling intravasal catheters upon free tissue grafts. First communication (author's transl)]. This is the first in a series of two papers reporting first results of studies made to set up a basic model of intraarterial perfusions in free tissue grafts. Epidermal tissue grafts were obtained from thirty-two domestic pigs prior to slaughtering and pervascularly perfused for twelve to ninety-six hours. Histological examinations showed that it is possible for tissue necrosis to be arrested as a prerequisite of subsequent in vivo experiments performed with the object of pervascularly supporting the healing-in of tissue grafts."} {"id": "PMID:160153", "title": "[Submicroscopic localization of endogenous peroxidase activity in the oral mucosal epithelium of man (author's transl)].", "content": "Using electron microscopy, the authors localized endogenous peroxidase activity in the buccal mucosal and alveolar process epithelium. A positive reaction could be demonstrated in all epithelial layers. The number of positive structures was greatest in the spinous layer. The reaction product is of a granular nature and is localized in the microperoxysomes. The reaction of lipofuscin granules, lysosomes, and telolysosomes in the upper epithelial layers is considered to be of none enzymatic origin. The importance of endogenous peroxidase to tissue is discussed in detail.", "contents": "[Submicroscopic localization of endogenous peroxidase activity in the oral mucosal epithelium of man (author's transl)]. Using electron microscopy, the authors localized endogenous peroxidase activity in the buccal mucosal and alveolar process epithelium. A positive reaction could be demonstrated in all epithelial layers. The number of positive structures was greatest in the spinous layer. The reaction product is of a granular nature and is localized in the microperoxysomes. The reaction of lipofuscin granules, lysosomes, and telolysosomes in the upper epithelial layers is considered to be of none enzymatic origin. The importance of endogenous peroxidase to tissue is discussed in detail."} {"id": "PMID:160154", "title": "[Injuries to the facial portion of the skull and their late effects in children and juveniles - a 10-year analysis (author's transl)].", "content": "A 10-year analysis comprising a total of 534 patients was used to study the histories of 192 puerile and juvenile patients with maxillofacial injuries. The proportion of children up to ten and fifteen years of age was 11.4 percent and 16.1 percent, respectively. Clinical and roentgenological reexaminations could be made of 139 patients. Typical fracture localizations and the frequency of late effects observed in the facial skeleton and dental system are discussed. It was possible for late damage to former tooth germs in the cleft of fracture to be observed in every second patient. Disturbances of growth after fractures of the body of mandible and the mid-facial skeleton were not noted. Among 33 patients with temporomandibular fractures, there were observed 5 cases showing different degrees of disturbed growth. The therapeutic approach chosen according to age and localization of fracture is described in detail.", "contents": "[Injuries to the facial portion of the skull and their late effects in children and juveniles - a 10-year analysis (author's transl)]. A 10-year analysis comprising a total of 534 patients was used to study the histories of 192 puerile and juvenile patients with maxillofacial injuries. The proportion of children up to ten and fifteen years of age was 11.4 percent and 16.1 percent, respectively. Clinical and roentgenological reexaminations could be made of 139 patients. Typical fracture localizations and the frequency of late effects observed in the facial skeleton and dental system are discussed. It was possible for late damage to former tooth germs in the cleft of fracture to be observed in every second patient. Disturbances of growth after fractures of the body of mandible and the mid-facial skeleton were not noted. Among 33 patients with temporomandibular fractures, there were observed 5 cases showing different degrees of disturbed growth. The therapeutic approach chosen according to age and localization of fracture is described in detail."} {"id": "PMID:160155", "title": "[Interdisciplinary cooperation of internists and maxillomandibular surgeons in the treatment of hemophiliacs (author's transl)].", "content": "The treatment of hemophiliacs at the Jena Center of Hemophilia is described from a stomatological point of view, the emphasis being on the advantage involved in treatment on an outpatient basis by close cooperation between stomatologists and internists. The clinical results obtained show quite clearly that this particular method of treatment has proved useful. Finally, the method of using GRF type adhesives is discussed critically, and substitution therapy, which is prerequisite to surgical operations performed on hemophiliacs, is recommended to be continued to be used.", "contents": "[Interdisciplinary cooperation of internists and maxillomandibular surgeons in the treatment of hemophiliacs (author's transl)]. The treatment of hemophiliacs at the Jena Center of Hemophilia is described from a stomatological point of view, the emphasis being on the advantage involved in treatment on an outpatient basis by close cooperation between stomatologists and internists. The clinical results obtained show quite clearly that this particular method of treatment has proved useful. Finally, the method of using GRF type adhesives is discussed critically, and substitution therapy, which is prerequisite to surgical operations performed on hemophiliacs, is recommended to be continued to be used."} {"id": "PMID:160156", "title": "[Studies on primary hyperparathyroidism with particular reference to osteal manifestations in the maxillofacial region (author's transl)].", "content": "After a brief review of the pathophysiological relationships determined for primary hyperparathyroidism, osteal manifestations of this condition are discussed. The importance of a histological demonstration of pathognomonic dissecting fibro-osteoclasia in iliac crest biopsy and in the marginal region of so-called brown tumors is pointed out in connection with results obtained by diagnosis in general and differential diagnosis in particular. The occurrence in the maxillofacial region of Recklinghausen's generalized fibrous osteodystrophy is described with reference to a particular case history, and the diagnostic value of clinical and roentgenological, laboratory-diagnosis and histological criteria is determined.", "contents": "[Studies on primary hyperparathyroidism with particular reference to osteal manifestations in the maxillofacial region (author's transl)]. After a brief review of the pathophysiological relationships determined for primary hyperparathyroidism, osteal manifestations of this condition are discussed. The importance of a histological demonstration of pathognomonic dissecting fibro-osteoclasia in iliac crest biopsy and in the marginal region of so-called brown tumors is pointed out in connection with results obtained by diagnosis in general and differential diagnosis in particular. The occurrence in the maxillofacial region of Recklinghausen's generalized fibrous osteodystrophy is described with reference to a particular case history, and the diagnostic value of clinical and roentgenological, laboratory-diagnosis and histological criteria is determined."} {"id": "PMID:160157", "title": "[Comparson of occlusal conditions in juveniles from residential areas with different drinking water fluoride contents (author's transl)].", "content": "The investigations reported in this paper were conducted in Karl-Marx-Stadt after 16 years from the introduction of drinking water fluoridation (1.0 ppm F), with a total of 792 randomly selected juveniles (whose average age was 14.9 years) being examined. Serving as a control group were 780 juveniles of the same age (15.4 years). The control persons were from Leipzig (0.2 ppm F). Included in the comparison with metric occlusal traits, use being made in this connection of the method for measuring occlusal traits, which was recommended in 1973 by an F.D.I. commission (COCSTOC-MOT). Despite the considerable reduction of caries in the deciduous dentition and the change in the eruptive behavior of permanent teeth, which is of great importance of the development, of dentition, no systematic differences could be observed between the two groups of subjects. An improvement in the occlusal conditions could not, after consumption of drinking water with an optimum fluoride content, be convincingly demonstrated by means of the epidemiological method used in these investigations.", "contents": "[Comparson of occlusal conditions in juveniles from residential areas with different drinking water fluoride contents (author's transl)]. The investigations reported in this paper were conducted in Karl-Marx-Stadt after 16 years from the introduction of drinking water fluoridation (1.0 ppm F), with a total of 792 randomly selected juveniles (whose average age was 14.9 years) being examined. Serving as a control group were 780 juveniles of the same age (15.4 years). The control persons were from Leipzig (0.2 ppm F). Included in the comparison with metric occlusal traits, use being made in this connection of the method for measuring occlusal traits, which was recommended in 1973 by an F.D.I. commission (COCSTOC-MOT). Despite the considerable reduction of caries in the deciduous dentition and the change in the eruptive behavior of permanent teeth, which is of great importance of the development, of dentition, no systematic differences could be observed between the two groups of subjects. An improvement in the occlusal conditions could not, after consumption of drinking water with an optimum fluoride content, be convincingly demonstrated by means of the epidemiological method used in these investigations."} {"id": "PMID:160158", "title": "[Thrombelastographic studies made to objectify the effects of Grisaldon upon the process of coagulation (author's transl)].", "content": "Thrombelastographic studies of the mode of action of Grisaldon showed that this preparation, unlike the pure substance of acetylsalicylic acid, has no appreciable coagulation-accelerating and fibrin-stabilizing effects. In addition, it was possible to show that an antifibrinolytic effect of the p-oxybenzoic acid propyl ester (Grisaldon component), which has been described in the literature, is not produced.", "contents": "[Thrombelastographic studies made to objectify the effects of Grisaldon upon the process of coagulation (author's transl)]. Thrombelastographic studies of the mode of action of Grisaldon showed that this preparation, unlike the pure substance of acetylsalicylic acid, has no appreciable coagulation-accelerating and fibrin-stabilizing effects. In addition, it was possible to show that an antifibrinolytic effect of the p-oxybenzoic acid propyl ester (Grisaldon component), which has been described in the literature, is not produced."} {"id": "PMID:160159", "title": "[Determining the overall density of permanent human teeth and its relation to the carrier's age (author's transl)].", "content": "(1) The pyknometer method was used to determine the specific gravity of the roots, central portions (necks), and crowns of 130 human teeth (incisors, canines, premolars, molars) obtained during autopsies. The overall density or specific gravity was calculated as the mean of the values obtained for these portions of permanent teeth. To test the relation between the total specific gravity and the carrier's individual age, a simple linear regression was calculated. It was not possible for a definite relation to be found between the specific gravities of teeth and the age of their carriers. (2) Limits to determining the individual age from the specific gravity of teeth are set especially by the factors discussed in this paper, by pathological influences, and by variations of specific gravity within isolated hard dental tissue. In human teeth, age-dependent physiosclerosis of bradytrophic tissue obviously is in the form of re- or transmineralization without major changes in the degree of mineralization and is usually overlapped by other phenomena. In addition, preparative and technical faults may result in false specific gravities being obtained. (3) Specific gravities of portions of teeth and total specific gravities determined therefrom cannot be used to find the carrier's age and, therefore, should be dismissed as means of identifying age by methods of forensic stomatology.", "contents": "[Determining the overall density of permanent human teeth and its relation to the carrier's age (author's transl)]. (1) The pyknometer method was used to determine the specific gravity of the roots, central portions (necks), and crowns of 130 human teeth (incisors, canines, premolars, molars) obtained during autopsies. The overall density or specific gravity was calculated as the mean of the values obtained for these portions of permanent teeth. To test the relation between the total specific gravity and the carrier's individual age, a simple linear regression was calculated. It was not possible for a definite relation to be found between the specific gravities of teeth and the age of their carriers. (2) Limits to determining the individual age from the specific gravity of teeth are set especially by the factors discussed in this paper, by pathological influences, and by variations of specific gravity within isolated hard dental tissue. In human teeth, age-dependent physiosclerosis of bradytrophic tissue obviously is in the form of re- or transmineralization without major changes in the degree of mineralization and is usually overlapped by other phenomena. In addition, preparative and technical faults may result in false specific gravities being obtained. (3) Specific gravities of portions of teeth and total specific gravities determined therefrom cannot be used to find the carrier's age and, therefore, should be dismissed as means of identifying age by methods of forensic stomatology."} {"id": "PMID:160160", "title": "[Experience in the treatment of pain-dysfunction syndromes by myogymnastic exercises with particular reference to 96 reexamined patients (author's transl)].", "content": "In 1975, a total of 165 patients with myoarthropathies were treated by myotherapy. Through the use of a program of step-by-step therapy, which included myogymnastic selftreatment in addition to psychotherpay and repair of teeth, 77.6 percent of 96 reexamined patients were made free from complaints. Fuller utilization of the possibilities of causal therapy would certainly have allowed a higher rate of success to be achieved using the simplified program of exercises described in this paper. Experimental evidence could be presented in support of the assumption that parodontal damage may be caused to uncorrected sites of abnormal occlusion in the course of myogymnastic therapy.", "contents": "[Experience in the treatment of pain-dysfunction syndromes by myogymnastic exercises with particular reference to 96 reexamined patients (author's transl)]. In 1975, a total of 165 patients with myoarthropathies were treated by myotherapy. Through the use of a program of step-by-step therapy, which included myogymnastic selftreatment in addition to psychotherpay and repair of teeth, 77.6 percent of 96 reexamined patients were made free from complaints. Fuller utilization of the possibilities of causal therapy would certainly have allowed a higher rate of success to be achieved using the simplified program of exercises described in this paper. Experimental evidence could be presented in support of the assumption that parodontal damage may be caused to uncorrected sites of abnormal occlusion in the course of myogymnastic therapy."} {"id": "PMID:160161", "title": "[Autoradiographic determinations of carbon-14-labeled monomers and residual monomers in the tissues of Wistar rats after implantation of cold-polymerizing polymethyl methacrylate (bone cement) (author's transl)].", "content": "Self-setting acrylics, named bone cement, are taken for the reconstruction of bone defects, for the fixation of endothesis and fractures. A disadvantage of these rapid-cure acrylic compounds is the toxicity of its monomer. Infraredspectrographic measurements showed an absolute content of 12,3 per cent monomer in an acrylic-resin-compound-implant. In order to perseive the incorporation of the diffused monomer after implantation of bone cement in rats, the monomer were marked with 14C (radioactive carbon). The autoradiographic examination revealed the excretion of the marked monomer in the urine and an accumulation in kidney, liver and lungs. The results were demonstrated.", "contents": "[Autoradiographic determinations of carbon-14-labeled monomers and residual monomers in the tissues of Wistar rats after implantation of cold-polymerizing polymethyl methacrylate (bone cement) (author's transl)]. Self-setting acrylics, named bone cement, are taken for the reconstruction of bone defects, for the fixation of endothesis and fractures. A disadvantage of these rapid-cure acrylic compounds is the toxicity of its monomer. Infraredspectrographic measurements showed an absolute content of 12,3 per cent monomer in an acrylic-resin-compound-implant. In order to perseive the incorporation of the diffused monomer after implantation of bone cement in rats, the monomer were marked with 14C (radioactive carbon). The autoradiographic examination revealed the excretion of the marked monomer in the urine and an accumulation in kidney, liver and lungs. The results were demonstrated."} {"id": "PMID:160170", "title": "[Phage typing and lysogen typing of Staphylococcus aureus].", "content": "A comparison was made between the results of phage and lysogenic typing of S. aureus strains isolated during several outbreaks of staphylococcal infection and S. aureus cultures isolated from the same carriers at different periods. The study of the groups of strains having the same origin showed that the differences in the number of reactions were more pronounced in lysogenic typing than in phage typing. For this reason lysogenic typing can be recommended only for the identification of those strains which cannot be identified with the use of the phages of the International Basic Set. The results of the experiments with induced phages proliferating in a restriction-defective strain indicated that restriction and modification were mainly responsible for the specificity of lytic reactions.", "contents": "[Phage typing and lysogen typing of Staphylococcus aureus]. A comparison was made between the results of phage and lysogenic typing of S. aureus strains isolated during several outbreaks of staphylococcal infection and S. aureus cultures isolated from the same carriers at different periods. The study of the groups of strains having the same origin showed that the differences in the number of reactions were more pronounced in lysogenic typing than in phage typing. For this reason lysogenic typing can be recommended only for the identification of those strains which cannot be identified with the use of the phages of the International Basic Set. The results of the experiments with induced phages proliferating in a restriction-defective strain indicated that restriction and modification were mainly responsible for the specificity of lytic reactions."} {"id": "PMID:160171", "title": "[Determination of sero- and biovariants of foreign and Soviet strains of Yersinia enterocolitica].", "content": "The results of the typing of the biochemical and serological variants of Yersinia enterocolitica strains from the USSR (10 strains) and other countries (32 strains) are presented. Most of these strains, belonging to biovars 1 and 5, could be determined with the use of the antigenic scheme which was proposed by Knapp only for biovars 2, 3 and 4. The strains isolated in Leningrad and in the Far East were found to belong to serovars 6,30; 7,8; 12,25 and 5B according to the scheme proposed by Wauters; of these, the last one corresponds to serovar IV in Knapp's scheme.", "contents": "[Determination of sero- and biovariants of foreign and Soviet strains of Yersinia enterocolitica]. The results of the typing of the biochemical and serological variants of Yersinia enterocolitica strains from the USSR (10 strains) and other countries (32 strains) are presented. Most of these strains, belonging to biovars 1 and 5, could be determined with the use of the antigenic scheme which was proposed by Knapp only for biovars 2, 3 and 4. The strains isolated in Leningrad and in the Far East were found to belong to serovars 6,30; 7,8; 12,25 and 5B according to the scheme proposed by Wauters; of these, the last one corresponds to serovar IV in Knapp's scheme."} {"id": "PMID:160172", "title": "[Immunomorphologic study of experimental enteric anc combined vaccination against cholera].", "content": "As a result of the enteral and combined subcutaneous-enteral immunization of adult rabbits with cholerogen toxoid and the specific fraction of chemical cholera vaccine in tablets immunological transformation occurred in the organism and a \"protective\" barrier consisting of antibody-containing cells was formed in the intestine on days 3-5. The combined method of immunization with cholera vaccine proved to be essentially as effective as enteral immunization in 2 administrations.", "contents": "[Immunomorphologic study of experimental enteric anc combined vaccination against cholera]. As a result of the enteral and combined subcutaneous-enteral immunization of adult rabbits with cholerogen toxoid and the specific fraction of chemical cholera vaccine in tablets immunological transformation occurred in the organism and a \"protective\" barrier consisting of antibody-containing cells was formed in the intestine on days 3-5. The combined method of immunization with cholera vaccine proved to be essentially as effective as enteral immunization in 2 administrations."} {"id": "PMID:160173", "title": "[Suppressing action of splenic cells on macrophage phagocytic activity].", "content": "The culture media withdrawn from 18-hour cultures of live spleen cells suppressed the phagocytic activity of peritoneal macrophages in mice. The level of suppression, as estimated for an equal number of spleen cells, varied in individual animals, which seemed to be connected with the level of normal infection in the animals. In the process of development of Ehrlich's carcinoma in mice suppressors were produced in the spleen in an increased amount, but only in connection with the total increase in the number of spleen cells, and not due to the selective accumulation of suppressor cells.", "contents": "[Suppressing action of splenic cells on macrophage phagocytic activity]. The culture media withdrawn from 18-hour cultures of live spleen cells suppressed the phagocytic activity of peritoneal macrophages in mice. The level of suppression, as estimated for an equal number of spleen cells, varied in individual animals, which seemed to be connected with the level of normal infection in the animals. In the process of development of Ehrlich's carcinoma in mice suppressors were produced in the spleen in an increased amount, but only in connection with the total increase in the number of spleen cells, and not due to the selective accumulation of suppressor cells."} {"id": "PMID:160177", "title": "[Scintigraphy in cardiomyopathy].", "content": "The function of the right ventricle (RV) and left ventricle (LV) was evaluated in 32 patients with congestive cardiomyopathies (COCM), 10 patients with hypertrophic cardiomyopathy (HOCM) and 21 normal subjects (N). In all these patients myocardial perfusion was analysed using quantitative 201 Tl myocardial perfusion imaging. In COCM parameters of RV and LV performance were significantly reduced (p less than 0.01); regional wall motion analysis revealed a reduced radial shortening ability. Regional Tl-distribution was not different in COCM and N; however, relative Tl-uptake was significantly reduced (p less than 0.05). 80% of all patients with COCM showed the RV free wall on Tl-perfusion scintigrams. These scintigraphic aspects allow a noninvasive differentiation of a disturbed LV function and the classification of coronary and primary myocardial etiology. In patients with COCM the scintigraphically determined thickness of septum and free wall of LV was increased as compared to N (p less than 0.05). The ratio septum/lateral wall of LV averaged 1.3 +/- 0.20. Quantitative analysis of regional Tl-uptake revealed increased segmental relative Tl-uptake. In the majority of patients there was a disproportionate septal hypertrophy on the gated blood pool scan in LAO. These radionuclide techniques allow a dynamic two-dimensional evaluation of the interventricular septum and the LV.", "contents": "[Scintigraphy in cardiomyopathy]. The function of the right ventricle (RV) and left ventricle (LV) was evaluated in 32 patients with congestive cardiomyopathies (COCM), 10 patients with hypertrophic cardiomyopathy (HOCM) and 21 normal subjects (N). In all these patients myocardial perfusion was analysed using quantitative 201 Tl myocardial perfusion imaging. In COCM parameters of RV and LV performance were significantly reduced (p less than 0.01); regional wall motion analysis revealed a reduced radial shortening ability. Regional Tl-distribution was not different in COCM and N; however, relative Tl-uptake was significantly reduced (p less than 0.05). 80% of all patients with COCM showed the RV free wall on Tl-perfusion scintigrams. These scintigraphic aspects allow a noninvasive differentiation of a disturbed LV function and the classification of coronary and primary myocardial etiology. In patients with COCM the scintigraphically determined thickness of septum and free wall of LV was increased as compared to N (p less than 0.05). The ratio septum/lateral wall of LV averaged 1.3 +/- 0.20. Quantitative analysis of regional Tl-uptake revealed increased segmental relative Tl-uptake. In the majority of patients there was a disproportionate septal hypertrophy on the gated blood pool scan in LAO. These radionuclide techniques allow a dynamic two-dimensional evaluation of the interventricular septum and the LV."} {"id": "PMID:160178", "title": "[Vagus mediated elevation of respiratory resistance in patients with acute myocardial infarction].", "content": "Changes in pulmonary function have been reported in patients after uncomplicated myocardial infarction, with reduction in lung volumes and flow rates. The significant increase in oscillatory resistance and impedance of the lung, was seen on the first day after myocardial infarction. The application of ipratropiumbromid, an anticholinergic broncholytic agent, significantly decreased oscillatory resistance and impedance, on the first day, but not to the same extent, after the fourth day. The reduction of oscillatory resistance and impedance could be attributed to blockade of a vagal mediated bronchoconstriction, which predominantly affects the small airways. The observed changes in pulmonary function, could therefore not only be due to congestion with increase in extravascular pulmonary fluid, but in the acute phase of myocardial infarction, also due to a reflex mechanism in which vagal mediated bronchoconstriction is demonstrated.", "contents": "[Vagus mediated elevation of respiratory resistance in patients with acute myocardial infarction]. Changes in pulmonary function have been reported in patients after uncomplicated myocardial infarction, with reduction in lung volumes and flow rates. The significant increase in oscillatory resistance and impedance of the lung, was seen on the first day after myocardial infarction. The application of ipratropiumbromid, an anticholinergic broncholytic agent, significantly decreased oscillatory resistance and impedance, on the first day, but not to the same extent, after the fourth day. The reduction of oscillatory resistance and impedance could be attributed to blockade of a vagal mediated bronchoconstriction, which predominantly affects the small airways. The observed changes in pulmonary function, could therefore not only be due to congestion with increase in extravascular pulmonary fluid, but in the acute phase of myocardial infarction, also due to a reflex mechanism in which vagal mediated bronchoconstriction is demonstrated."} {"id": "PMID:160179", "title": "Thymus actin: preparation and characterization.", "content": "A combination of the C-gamma alumina adsorption technique of Lindberg, U. Skoog, L. 1970. Eur. J. Biochem. 13 326-335 with the traditional actin purification procedure (polymerization-depolymerization) yielded a simple method for the preparation of actin from fresh or acetone-dried thymus tissue. Actin obtained by this procedure from thymus was homogeneous and comigrated with skeletal actin in SDS gel electrophoresis. In isoelectric focusing it was shown to contain beta and gamma actin. Thymus actin polymerized poorly or not at all. It was native, however, as judged from its DN-ase I inhibiting activity which equalled that of skeletal actin. It also activated skeletal myosin ATP-ase but to a lesser extent than skeletal actin. On addition of HMM to thymus G actin, decorated filaments formed abundantly.", "contents": "Thymus actin: preparation and characterization. A combination of the C-gamma alumina adsorption technique of Lindberg, U. Skoog, L. 1970. Eur. J. Biochem. 13 326-335 with the traditional actin purification procedure (polymerization-depolymerization) yielded a simple method for the preparation of actin from fresh or acetone-dried thymus tissue. Actin obtained by this procedure from thymus was homogeneous and comigrated with skeletal actin in SDS gel electrophoresis. In isoelectric focusing it was shown to contain beta and gamma actin. Thymus actin polymerized poorly or not at all. It was native, however, as judged from its DN-ase I inhibiting activity which equalled that of skeletal actin. It also activated skeletal myosin ATP-ase but to a lesser extent than skeletal actin. On addition of HMM to thymus G actin, decorated filaments formed abundantly."} {"id": "PMID:160182", "title": "The mechanism of release of hepatic enzymes in various liver diseases. II. Altered activity ratios of GOT to GPT in serum and liver of patients with liver diseases.", "content": "The activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase (GLD) were determined in liver biopsy specimens and sera of patients with various liver diseases. Mitochondrial and cytosol isozymes of GOT were also separated for their assay. The activity ratio of GOT/GPT in serum was found to reflect the ratio in liver cytosol. The increased ratio in advanced or severe liver diseases, such as liver cirrhosis, was due to the greater decrease in liver cytosol GPT activity, this being pronounced in primary hepatoma. The activity of GLD decreased similarly but less markedly. The relatively greater decrease in GPT compared with GOT in advanced liver diseases was not mainly due to leakage of the enzyme from the liver, but to a specific mechanism associated with hepatic injury or its progression. Other pathological conditions of the liver such as those in obstructive jaundice and alcoholic liver injury also appeared to result in reduced liver GPT activity, which was reflected in the serum as an increased GOT/GPT ratio.", "contents": "The mechanism of release of hepatic enzymes in various liver diseases. II. Altered activity ratios of GOT to GPT in serum and liver of patients with liver diseases. The activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase (GLD) were determined in liver biopsy specimens and sera of patients with various liver diseases. Mitochondrial and cytosol isozymes of GOT were also separated for their assay. The activity ratio of GOT/GPT in serum was found to reflect the ratio in liver cytosol. The increased ratio in advanced or severe liver diseases, such as liver cirrhosis, was due to the greater decrease in liver cytosol GPT activity, this being pronounced in primary hepatoma. The activity of GLD decreased similarly but less markedly. The relatively greater decrease in GPT compared with GOT in advanced liver diseases was not mainly due to leakage of the enzyme from the liver, but to a specific mechanism associated with hepatic injury or its progression. Other pathological conditions of the liver such as those in obstructive jaundice and alcoholic liver injury also appeared to result in reduced liver GPT activity, which was reflected in the serum as an increased GOT/GPT ratio."} {"id": "PMID:160183", "title": "The tumor-forming type of multiple myeloma. I. Biological behavior.", "content": "A total of 45 cases of multiple myeloma has been followed up clinically during the period from 7 to 80 months. Out of these, six patients (13.3%) were diagnosed to be the tumor-forming type; they developed discrete tumor formation at the disease onset or during clinical observation. Biological behavior of these cases is briefly outlined. Histologically, five cases presented with well or moderately well differentiated plasma cells according to the grading made by Pasmantier and Azar. The remaining one case was poorly differentiated in cell maturity, and with electron and immunofluorescence microscopies, proved to be of plasmacytic nature.", "contents": "The tumor-forming type of multiple myeloma. I. Biological behavior. A total of 45 cases of multiple myeloma has been followed up clinically during the period from 7 to 80 months. Out of these, six patients (13.3%) were diagnosed to be the tumor-forming type; they developed discrete tumor formation at the disease onset or during clinical observation. Biological behavior of these cases is briefly outlined. Histologically, five cases presented with well or moderately well differentiated plasma cells according to the grading made by Pasmantier and Azar. The remaining one case was poorly differentiated in cell maturity, and with electron and immunofluorescence microscopies, proved to be of plasmacytic nature."} {"id": "PMID:160184", "title": "Effects of vagotomy on feeding and defecation in guinea pigs.", "content": "The effect of subdiaphragmatic vagotomy on food intake and defecation was studied in guinea pigs. Weights of food and feces were measured for at least three weeks after vagotomy. The weight of daily food intake and feces evacuated increased about 15 and 30% after vagotomy compared with controls whereas it did not change in sham operated animals. The weight of scybalum decreased after vagotomy although the number increased markedly. It was considered that an increase in food intake after vagotomy may result from blocking of satiety signals mediated by the vagus; moreover, that the increase in feces may depend on the enhancement of scybalum formation in the proximal colon resulting from increasing food intake and transportation of the larger amount of the contents after vagotomy.", "contents": "Effects of vagotomy on feeding and defecation in guinea pigs. The effect of subdiaphragmatic vagotomy on food intake and defecation was studied in guinea pigs. Weights of food and feces were measured for at least three weeks after vagotomy. The weight of daily food intake and feces evacuated increased about 15 and 30% after vagotomy compared with controls whereas it did not change in sham operated animals. The weight of scybalum decreased after vagotomy although the number increased markedly. It was considered that an increase in food intake after vagotomy may result from blocking of satiety signals mediated by the vagus; moreover, that the increase in feces may depend on the enhancement of scybalum formation in the proximal colon resulting from increasing food intake and transportation of the larger amount of the contents after vagotomy."} {"id": "PMID:160185", "title": "Effect of glucose and oxygen on the structure of the plasma membrane of Staphylococcus aureus.", "content": "The effects of glucose and oxygen on the formation of the plasma membrane of Staphylococcus aureus were studied. Phospholipids were consistent components of the membrane and were not affected by glucose or oxygen. Phospholipid fatty acids in cells grown in glucose containing media were rich in Ceven (C18, C20) fatty acid chains, whereas cells grown in glucose deficient media (normal broth) had anteiso Codd (C15,C17) fatty acid chains in place of Ceven chains. This may indicate increased membrane rigidity of the cells grown in glucose containing media. Cytochromes and ATPase were present in the membrane from cells grown in normal broth, but were deficient in the cells grown in glucose containing media. Polypeptide analysis of the membrane proteins showed a deficiency of the bands corresponding to these enzymes. They were not induced by the additionof oxygen to cells grown in glucose containing media. It was concluded that glucose was the dominant factor inhibiting the formation of these membrane enzymes.", "contents": "Effect of glucose and oxygen on the structure of the plasma membrane of Staphylococcus aureus. The effects of glucose and oxygen on the formation of the plasma membrane of Staphylococcus aureus were studied. Phospholipids were consistent components of the membrane and were not affected by glucose or oxygen. Phospholipid fatty acids in cells grown in glucose containing media were rich in Ceven (C18, C20) fatty acid chains, whereas cells grown in glucose deficient media (normal broth) had anteiso Codd (C15,C17) fatty acid chains in place of Ceven chains. This may indicate increased membrane rigidity of the cells grown in glucose containing media. Cytochromes and ATPase were present in the membrane from cells grown in normal broth, but were deficient in the cells grown in glucose containing media. Polypeptide analysis of the membrane proteins showed a deficiency of the bands corresponding to these enzymes. They were not induced by the additionof oxygen to cells grown in glucose containing media. It was concluded that glucose was the dominant factor inhibiting the formation of these membrane enzymes."} {"id": "PMID:160186", "title": "Vectorcardiogram of complete right bundle branch block with left axis deviation by the Frank and Kimura systems.", "content": "Vectorcardiogram (VCG) recorded by both the Frank and Kimura systems were examined in 45 patients with complete right bundle branch block (RBBB) and left axis deviation (LAD) to investigate the relationship seen on electrocardiogram (ECG) between RBBB with LAD and bilateral bundle. The sample included: 13 cases of type SI, SII, SIII, SaVF; 21 cases of type SI, SII, SIII, aVF; and 11 cases of types SI, SII, SIII. VCG recorded by the Frank system were classified into seven types according to the QRS loop pattern on the frontal plane and into three types according to the horizontal plane. The main findings were: (a) In the Frank system the QRS loop in the frontal plane showed a variety of patterns in RBBB with LAD. (b) On VCG of complete RBBB judged complicated by a left anterior hemiblock by the Frank system, the main portion of the QRS loop extended to the left superior or merely to the left in the frontal plane. The direction of rotation and position on the horizontal plane were not consistent. (c) The results of this study suggest the usefulness of the Kimura system as an auxiliary diagnostic technique.", "contents": "Vectorcardiogram of complete right bundle branch block with left axis deviation by the Frank and Kimura systems. Vectorcardiogram (VCG) recorded by both the Frank and Kimura systems were examined in 45 patients with complete right bundle branch block (RBBB) and left axis deviation (LAD) to investigate the relationship seen on electrocardiogram (ECG) between RBBB with LAD and bilateral bundle. The sample included: 13 cases of type SI, SII, SIII, SaVF; 21 cases of type SI, SII, SIII, aVF; and 11 cases of types SI, SII, SIII. VCG recorded by the Frank system were classified into seven types according to the QRS loop pattern on the frontal plane and into three types according to the horizontal plane. The main findings were: (a) In the Frank system the QRS loop in the frontal plane showed a variety of patterns in RBBB with LAD. (b) On VCG of complete RBBB judged complicated by a left anterior hemiblock by the Frank system, the main portion of the QRS loop extended to the left superior or merely to the left in the frontal plane. The direction of rotation and position on the horizontal plane were not consistent. (c) The results of this study suggest the usefulness of the Kimura system as an auxiliary diagnostic technique."} {"id": "PMID:160187", "title": "Tumor induction in Swiss mice by filtrable agent and Salmonella typhimurium.", "content": "Combined inoculation of a cell-free extract of leukotic tissue of D103 mice and Salmonella typhimurium into adult Swiss mice induced leukosis and solid tumors. The induced solid tumors were histologically multifarious, and were transplantable in Swiss mice, but not in other strains of mice.", "contents": "Tumor induction in Swiss mice by filtrable agent and Salmonella typhimurium. Combined inoculation of a cell-free extract of leukotic tissue of D103 mice and Salmonella typhimurium into adult Swiss mice induced leukosis and solid tumors. The induced solid tumors were histologically multifarious, and were transplantable in Swiss mice, but not in other strains of mice."} {"id": "PMID:160188", "title": "Preparation of anti-rat albumin antiserum and its application to radioimmunoassay.", "content": "Albumin was highly purified from a commercially available rat albumin preparation (Fraction V) using disc electrophoresis. The purified albumin had the same antigenicity as Fraction V. A monospecific anti-rat albumin rabbit serum was obtained. The antiserum was used in a double antibody quantitative method for determining rat albumin.", "contents": "Preparation of anti-rat albumin antiserum and its application to radioimmunoassay. Albumin was highly purified from a commercially available rat albumin preparation (Fraction V) using disc electrophoresis. The purified albumin had the same antigenicity as Fraction V. A monospecific anti-rat albumin rabbit serum was obtained. The antiserum was used in a double antibody quantitative method for determining rat albumin."} {"id": "PMID:160191", "title": "Changes of prekallikrein in the cases with disseminated intravascular coagulation syndrome.", "content": "Changes of prekallikrein in the cases with DIC were investigated, i.e., DIC cases including disseminated metastasis of gastric cancer, acute promyelocytic leukemia and endotoxin shock. Therefore, the trigger substances for this paper were the pathologic cells of the leukemia, the cultured well differentiated adenocarcinoma cells and endotoxin. (1) The lysates of the pathologic cells of the leukemia and the cultured cells showed prekallikrein activation. Endotoxin showed prekallikrein activation via factor XII. (2) Serine proteases (factor Xa, thrombin, plasmin and trypsin) activated prekallikrein in the plasma and the purified prekallikrein. (3) Antithrombin III, aprotinin and FOY inhibited prekallikrein activation. Antithrombin III was promoted by heparin in its inhibitory effect.", "contents": "Changes of prekallikrein in the cases with disseminated intravascular coagulation syndrome. Changes of prekallikrein in the cases with DIC were investigated, i.e., DIC cases including disseminated metastasis of gastric cancer, acute promyelocytic leukemia and endotoxin shock. Therefore, the trigger substances for this paper were the pathologic cells of the leukemia, the cultured well differentiated adenocarcinoma cells and endotoxin. (1) The lysates of the pathologic cells of the leukemia and the cultured cells showed prekallikrein activation. Endotoxin showed prekallikrein activation via factor XII. (2) Serine proteases (factor Xa, thrombin, plasmin and trypsin) activated prekallikrein in the plasma and the purified prekallikrein. (3) Antithrombin III, aprotinin and FOY inhibited prekallikrein activation. Antithrombin III was promoted by heparin in its inhibitory effect."} {"id": "PMID:160192", "title": "Sodium-independent, high-affinity binding of [3H]gamma-aminobutyric acid in human neurological disorders.", "content": "With respect to [3H]GABA-binding in material prepared from human post-mortem brain, the following observations have been made: (1) The [3H]GABA binding site in the cerebellum has the pharmacological characteristics of the physiological GABA-receptor observed in other species. Together with the post-mortem stability exhibited for [3H]GABA-binding, this provides an approach for determining the functional state of the GABA-receptor in various disease states; (2) In Parkinson's disease [3H]GABA-binding in the substantia nigra is significantly decreased whereas that in the putamen and caudate nucleus is unaltered. The former finding likely indicates that GABA binding sites (receptors) occur on nigral dopaminergic cell bodies and/or dendrites. The latter finding may signify that relatively few of the striatal [3H]GABA binding sites occur on dopaminergic nerve terminals in the human caudate or putamen; (3) In Huntington's disease [3H]GABA binding was decreased in the caudate nucleus and putamen, in parallel wih the massive cell loss and gliosis observed in this condition. Membranes prepared from cerebellar tissue of these patients possessed an increased affinity for [3H]GABA-binding; (4) Pre-treatment of cerebellar membranes from control brains with Triton-X-100 (0.02%) or phospholipase-C (0.001 units) results in kinetic changes very similar to those observed in Huntington's brains. In contrast, such treatment was virtually without effect on the IC50 or KD for [3H]GABA on cerebellar membranes prepared from Huntington's brains; (5) These results imply that a phospholipid, possibly related to phosphoglycerolethanolamine, is altered in the membrranes of Huntington's patients and that this phospholipid normally has a role in controlling accessibility to the GABA-receptor.", "contents": "Sodium-independent, high-affinity binding of [3H]gamma-aminobutyric acid in human neurological disorders. With respect to [3H]GABA-binding in material prepared from human post-mortem brain, the following observations have been made: (1) The [3H]GABA binding site in the cerebellum has the pharmacological characteristics of the physiological GABA-receptor observed in other species. Together with the post-mortem stability exhibited for [3H]GABA-binding, this provides an approach for determining the functional state of the GABA-receptor in various disease states; (2) In Parkinson's disease [3H]GABA-binding in the substantia nigra is significantly decreased whereas that in the putamen and caudate nucleus is unaltered. The former finding likely indicates that GABA binding sites (receptors) occur on nigral dopaminergic cell bodies and/or dendrites. The latter finding may signify that relatively few of the striatal [3H]GABA binding sites occur on dopaminergic nerve terminals in the human caudate or putamen; (3) In Huntington's disease [3H]GABA binding was decreased in the caudate nucleus and putamen, in parallel wih the massive cell loss and gliosis observed in this condition. Membranes prepared from cerebellar tissue of these patients possessed an increased affinity for [3H]GABA-binding; (4) Pre-treatment of cerebellar membranes from control brains with Triton-X-100 (0.02%) or phospholipase-C (0.001 units) results in kinetic changes very similar to those observed in Huntington's brains. In contrast, such treatment was virtually without effect on the IC50 or KD for [3H]GABA on cerebellar membranes prepared from Huntington's brains; (5) These results imply that a phospholipid, possibly related to phosphoglycerolethanolamine, is altered in the membrranes of Huntington's patients and that this phospholipid normally has a role in controlling accessibility to the GABA-receptor."} {"id": "PMID:160194", "title": "Expectations of teachers for physically handicapped and normal first grade students.", "content": "A descriptive study was conducted to determine whether teachers held different student role expectations for physically handicapped first grade students than they did for physically normal students. Contrary to predictions, results demonstrated that the teachers held statistically significantly higher expectations for the physically handicapped students. Such differences might be due to social desirability (responding in what appears to be a socially acceptable manner), or to a \"haloing\" of expectations for physically handicapped students. The teachers' inflated expectations could result in negative reactions toward handicapped students who do not demonstrate anticipated behaviors or live up to inflated expectations.", "contents": "Expectations of teachers for physically handicapped and normal first grade students. A descriptive study was conducted to determine whether teachers held different student role expectations for physically handicapped first grade students than they did for physically normal students. Contrary to predictions, results demonstrated that the teachers held statistically significantly higher expectations for the physically handicapped students. Such differences might be due to social desirability (responding in what appears to be a socially acceptable manner), or to a \"haloing\" of expectations for physically handicapped students. The teachers' inflated expectations could result in negative reactions toward handicapped students who do not demonstrate anticipated behaviors or live up to inflated expectations."} {"id": "PMID:160197", "title": "A new grouping of intrafusal muscle fibers based on developmental studies of muscle spindles in the cat.", "content": "The development of muscle spindles was studied using the tenuissimus muscle of the cat. Observations show that the intrafusal muscle fibers develop as two separate groups: one group represented by a single nuclear bag fiber while the second group comprises the second nuclear bag fiber in association with all the nuclear chain fibers. This grouping is most pronounced in the fetus and is clearly seen in neonatal kittens (i.e., up to 2 weeks of age). As the intrafusal fibers begin to separate from each other, the groupings become less noticeable, although this basic pattern is often retained in the adult. The pattern of intrafusal fiber grouping is most noticeable in the equatorial regions of the spindle and least noticeable in the polar regions. This is not the grouping of fibers which would have been expected from a consideration of existing reports on muscle spindles. The implications for spindle form and function are considered.", "contents": "A new grouping of intrafusal muscle fibers based on developmental studies of muscle spindles in the cat. The development of muscle spindles was studied using the tenuissimus muscle of the cat. Observations show that the intrafusal muscle fibers develop as two separate groups: one group represented by a single nuclear bag fiber while the second group comprises the second nuclear bag fiber in association with all the nuclear chain fibers. This grouping is most pronounced in the fetus and is clearly seen in neonatal kittens (i.e., up to 2 weeks of age). As the intrafusal fibers begin to separate from each other, the groupings become less noticeable, although this basic pattern is often retained in the adult. The pattern of intrafusal fiber grouping is most noticeable in the equatorial regions of the spindle and least noticeable in the polar regions. This is not the grouping of fibers which would have been expected from a consideration of existing reports on muscle spindles. The implications for spindle form and function are considered."} {"id": "PMID:160199", "title": "Years of life lost due to Huntington disease.", "content": "Many genetic diseases shorten the lives of people who have them. Hence, it makes sense to speak of years of life lost due to cystic fibrosis or sickle-cell anemia or numerous other genetic disorders. In conventional practice, years of life lost is calculated for causes of death only, but a genetic disease is better understood as a risk-altering state or condition: it acts not at the time of death only but from birth onwards. Therefore, we must reformulate the concept of years of life lost before applying it to genetic conditions. This has already been done for congenital genetic diseases. This paper extends the reformulation to diseases with delayed onset. Huntington disease (HD) is used as an example.", "contents": "Years of life lost due to Huntington disease. Many genetic diseases shorten the lives of people who have them. Hence, it makes sense to speak of years of life lost due to cystic fibrosis or sickle-cell anemia or numerous other genetic disorders. In conventional practice, years of life lost is calculated for causes of death only, but a genetic disease is better understood as a risk-altering state or condition: it acts not at the time of death only but from birth onwards. Therefore, we must reformulate the concept of years of life lost before applying it to genetic conditions. This has already been done for congenital genetic diseases. This paper extends the reformulation to diseases with delayed onset. Huntington disease (HD) is used as an example."} {"id": "PMID:160202", "title": "The questionnaire to parents of children with the Down syndrome: how to inform the parents and psychological responses to counseling.", "content": "This study determined the experience of 137 sets of parents when they were informed that their child had Down syndrome and how they would have preferred this matter to have been handled. The survey revealed that the majority of parents would have preferred being told as soon as possible, with both of them present, and that they had suspected something wrong at the birth of the child. This information prompted us to analyze critically the parental experiences and to formulate a positive approach, with sensitive, supportive, and progressive counseling.", "contents": "The questionnaire to parents of children with the Down syndrome: how to inform the parents and psychological responses to counseling. This study determined the experience of 137 sets of parents when they were informed that their child had Down syndrome and how they would have preferred this matter to have been handled. The survey revealed that the majority of parents would have preferred being told as soon as possible, with both of them present, and that they had suspected something wrong at the birth of the child. This information prompted us to analyze critically the parental experiences and to formulate a positive approach, with sensitive, supportive, and progressive counseling."} {"id": "PMID:160204", "title": "Laparoscopic sterilization with the spring clip: instrumentation development and current clinical experience.", "content": "Since the original spring clip sterilization studies were reported, a number of clinically important modifications to the spring clip and applicator have been developed. The spring-loaded clip, manufactured by Richard Wolf Medical Instruments Corporation of Chicago, Illinois, and Rocket of London, Inc., London, England, and New York, New York can be applied with either a one- or two-incision applicator and the clips and applicators currently available incorporate improvements to the original prototypes in design, manufacture, and quality control. The two-incision applicator is associated with significantly fewer misapplications and the high pregnancy rates reported with the original clip and applicator have not occurred with the current designs. Comparative studies between the clip and band have revealed less operative bleeding and pain associated with the clip. The method is appropriate to all women requesting sterilization but especially to those in the younger age group who may subsequently request reversal because of divorce and remarriage.", "contents": "Laparoscopic sterilization with the spring clip: instrumentation development and current clinical experience. Since the original spring clip sterilization studies were reported, a number of clinically important modifications to the spring clip and applicator have been developed. The spring-loaded clip, manufactured by Richard Wolf Medical Instruments Corporation of Chicago, Illinois, and Rocket of London, Inc., London, England, and New York, New York can be applied with either a one- or two-incision applicator and the clips and applicators currently available incorporate improvements to the original prototypes in design, manufacture, and quality control. The two-incision applicator is associated with significantly fewer misapplications and the high pregnancy rates reported with the original clip and applicator have not occurred with the current designs. Comparative studies between the clip and band have revealed less operative bleeding and pain associated with the clip. The method is appropriate to all women requesting sterilization but especially to those in the younger age group who may subsequently request reversal because of divorce and remarriage."} {"id": "PMID:160205", "title": "Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy.", "content": "Paired-pulse stimulation induced larger aftercontractions in papillary muscles from spontaneously hypertensive rats (SHR) than from normotensive Wistar-Kyoto rats (WKY). To determine whether aftercontraction exaggeration is a general characteristic of hypertrophied cardiac muscle, three models were examined: SHRs, deoxycorticosterone acetate (DOCA)-treated rats, and aorta-constricted rats. Responses of pipillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to pipillary muscles from WKY or sham-treated controls, respectively. Field-stimulated papillary muscles mounted in an oxygenated temperature-controlled physiologic salt solution were exposed to calcium concentrations of 2.5 and 5.0 mM, and temperatures of 27 degrees C and 17 degrees C. Although testing conditions influenced the contractile responses to single stimuli, there was no difference in active tension, time to peak tension, or one-half relaxation time between the three experimental groups and their respective controls. Paired-pulse stimulation induced aftercontractions that were enhanced in high-calcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls.", "contents": "Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy. Paired-pulse stimulation induced larger aftercontractions in papillary muscles from spontaneously hypertensive rats (SHR) than from normotensive Wistar-Kyoto rats (WKY). To determine whether aftercontraction exaggeration is a general characteristic of hypertrophied cardiac muscle, three models were examined: SHRs, deoxycorticosterone acetate (DOCA)-treated rats, and aorta-constricted rats. Responses of pipillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to pipillary muscles from WKY or sham-treated controls, respectively. Field-stimulated papillary muscles mounted in an oxygenated temperature-controlled physiologic salt solution were exposed to calcium concentrations of 2.5 and 5.0 mM, and temperatures of 27 degrees C and 17 degrees C. Although testing conditions influenced the contractile responses to single stimuli, there was no difference in active tension, time to peak tension, or one-half relaxation time between the three experimental groups and their respective controls. Paired-pulse stimulation induced aftercontractions that were enhanced in high-calcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls."} {"id": "PMID:160200", "title": "Shunt nephritis: demonstration of diphtheroid antigen in glomeruli.", "content": "A 23-year-old girl with a ventriculo-atrial shunt presented with hematuria, proteinuria and severe oedema. Diphtheroid organisms were cultured from blood, cerebrospinal fluid and the shung valve. Immunoglobulin, complement components and diphtheroid antigenic material were demonstrated in the glomeruli by immunofluorescence microscopy. Treatment of her shunt infection by shunt replacement and antibiotic therapy resulted in slow resolution of her nephritis. The slow resolution of her nephritis suggests that prompt resolution of immune complex disease due to prolonged bacterial injection cannot always be anticipated, even after successful eradication of infection.", "contents": "Shunt nephritis: demonstration of diphtheroid antigen in glomeruli. A 23-year-old girl with a ventriculo-atrial shunt presented with hematuria, proteinuria and severe oedema. Diphtheroid organisms were cultured from blood, cerebrospinal fluid and the shung valve. Immunoglobulin, complement components and diphtheroid antigenic material were demonstrated in the glomeruli by immunofluorescence microscopy. Treatment of her shunt infection by shunt replacement and antibiotic therapy resulted in slow resolution of her nephritis. The slow resolution of her nephritis suggests that prompt resolution of immune complex disease due to prolonged bacterial injection cannot always be anticipated, even after successful eradication of infection."} {"id": "PMID:160206", "title": "Increased passive stiffness of short-term pressure-overload hypertrophied myocardium in cat.", "content": "The passive stress-strain relationship of right ventricular papillary muscles from 10 normal and 9 experimental cats with short-term pressure-overload right ventricular hypertrophy-failure was examined by plotting the logarithm of instantaneous stress (ln sigma) against the natural strain calculated as ln(l/l0) where l = instantaneous length and l0 = length at zero force. Such a stress-strain relationship was well approximated by a linear relationship. The slope K obtained from this linear relationship was higher in the hypertrophy-failure muscles (normal, 15.01 +/- 0.87 (SEM); hypertrophy-failure, 31.79 +/- 4.09; P less than 0.005). The value of the intercept, ln C was similar in the two groups (normal, -4.33 +/- 0.20; hypertrophy-failure, -4.71 +/- 0.10). This analysis indicates the the ln sigma-natural strain relationship is linear in the papillary muscle and the slope of this relationship, an index of stiffness, is increased in hypertrophy-failure muscles. Using a three-element muscle model, it is shown that increased diastolic stiffness may contribute to the decreased systolic performance.", "contents": "Increased passive stiffness of short-term pressure-overload hypertrophied myocardium in cat. The passive stress-strain relationship of right ventricular papillary muscles from 10 normal and 9 experimental cats with short-term pressure-overload right ventricular hypertrophy-failure was examined by plotting the logarithm of instantaneous stress (ln sigma) against the natural strain calculated as ln(l/l0) where l = instantaneous length and l0 = length at zero force. Such a stress-strain relationship was well approximated by a linear relationship. The slope K obtained from this linear relationship was higher in the hypertrophy-failure muscles (normal, 15.01 +/- 0.87 (SEM); hypertrophy-failure, 31.79 +/- 4.09; P less than 0.005). The value of the intercept, ln C was similar in the two groups (normal, -4.33 +/- 0.20; hypertrophy-failure, -4.71 +/- 0.10). This analysis indicates the the ln sigma-natural strain relationship is linear in the papillary muscle and the slope of this relationship, an index of stiffness, is increased in hypertrophy-failure muscles. Using a three-element muscle model, it is shown that increased diastolic stiffness may contribute to the decreased systolic performance."} {"id": "PMID:160211", "title": "Abnormal keratan sulphate excretion.", "content": "Simple methods for the detection of keratan sulphate in urine have been applied to over 300 urine samples collected from children and adults with bone and cartilage dysplasias with or without mental retardation. Abnormal keratan sulphate excretion, which is a feature of type IV mucopolysaccharidosis (Morquio syndrome), is found in patients with that condition only during childhood. Abnormal excretion is also a feature of Kniest dysplasia and GM1 gangliosidosis and may be present in a number of other bone and cartilage dysplasias of unknown aetiology.", "contents": "Abnormal keratan sulphate excretion. Simple methods for the detection of keratan sulphate in urine have been applied to over 300 urine samples collected from children and adults with bone and cartilage dysplasias with or without mental retardation. Abnormal keratan sulphate excretion, which is a feature of type IV mucopolysaccharidosis (Morquio syndrome), is found in patients with that condition only during childhood. Abnormal excretion is also a feature of Kniest dysplasia and GM1 gangliosidosis and may be present in a number of other bone and cartilage dysplasias of unknown aetiology."} {"id": "PMID:160207", "title": "Correlation studies of morphological and biochemical parameters in human ejaculate in various andrological diagnoses. 3rd report. Correlations between morphological and biochemical parameters.", "content": "The result of a study of correlations between morphological and biochemical parameters in human ejaculate is presented in conclusion of an extensive study of these parameters. Basing on these results, for which a statistical significance of p less than 0.05 was calculated, it can be stated that higher fructose concentrations are associated with lower sperm density; at the same time, the higher fructose concentrations correlate with a higher percentage of non-motile and of pathologically changed spermatozoa. Similar associations can be established for certain substrates which result from fructolysis. The possibility of diffusion of enzymes from the cellular components must be considered as regards the increased activities of PGK, PGI and ATPase in seminal plasma in the presence of greater sperm density. Reliable conclusions about associations between morphological characteristics and enzyme activities can be expected in the future from appropriate measurements in the cellular elements (spermatozoa, round cells) of the ejaculate. The study results provide a further insight into the biochemistry of seminal plasma and into the associations between morphological and biochemical parameters in the ejaculate.", "contents": "Correlation studies of morphological and biochemical parameters in human ejaculate in various andrological diagnoses. 3rd report. Correlations between morphological and biochemical parameters. The result of a study of correlations between morphological and biochemical parameters in human ejaculate is presented in conclusion of an extensive study of these parameters. Basing on these results, for which a statistical significance of p less than 0.05 was calculated, it can be stated that higher fructose concentrations are associated with lower sperm density; at the same time, the higher fructose concentrations correlate with a higher percentage of non-motile and of pathologically changed spermatozoa. Similar associations can be established for certain substrates which result from fructolysis. The possibility of diffusion of enzymes from the cellular components must be considered as regards the increased activities of PGK, PGI and ATPase in seminal plasma in the presence of greater sperm density. Reliable conclusions about associations between morphological characteristics and enzyme activities can be expected in the future from appropriate measurements in the cellular elements (spermatozoa, round cells) of the ejaculate. The study results provide a further insight into the biochemistry of seminal plasma and into the associations between morphological and biochemical parameters in the ejaculate."} {"id": "PMID:160212", "title": "Huntington's disease: abnormality of lymphocyte capping.", "content": "Concanavalin A-induced lymphocyte capping was studied in 30 patients with Huntington's disease (HD) and 39 controls. A significant decrease in lymphocyte capping was seen in the 24 patients with HD less than 60 years of age compared to 25 age-matched controls (p less than 0.01); above age 60, differences between patients with HD and controls were not significant. These findings lend support to previous observations that generalized membrane abnormalities are present in patients with HD. Studies of HD lymphocyte capping may permit a detailed analysis of membrane function in cells that are readily obtained from living patients.", "contents": "Huntington's disease: abnormality of lymphocyte capping. Concanavalin A-induced lymphocyte capping was studied in 30 patients with Huntington's disease (HD) and 39 controls. A significant decrease in lymphocyte capping was seen in the 24 patients with HD less than 60 years of age compared to 25 age-matched controls (p less than 0.01); above age 60, differences between patients with HD and controls were not significant. These findings lend support to previous observations that generalized membrane abnormalities are present in patients with HD. Studies of HD lymphocyte capping may permit a detailed analysis of membrane function in cells that are readily obtained from living patients."} {"id": "PMID:160216", "title": "[Heart valve prostheses in children with reference to 95 cases].", "content": "Over a 10 year period, 95 children aged 15 years and less underwent replacement of one or several of their heart valves, usually by a Starr-Edwards ball prosthesis. The predominant pathology was rheumatic heart disease and the most commonly affected valve was the mitral. Severe symptomatology, heart failure, cardiomegaly and high wedged-capillary and pulmonary arterial pressures were practically constant findings. Operative mortality was low (3.2%) and the long-term mortality was 10 patients. With an average follow-up of 40 months, results were excellent in the great majority of patients, with complete regression of symptoms, cardiomegaly and high capillary and pulmonary arterial pressures. Anticoagulant therapy was not systematic and only half the series were so treated. Thromboembolic complications were rare, 5.5% patients, but only affected those without anticoagulant therapy. The problems of evolving rheumatic disease and, above all, of tricuspid incompetence, the persistence of which after surgery on the mitral valve seems to be a sign of advanced myocardial damage, are discussed.", "contents": "[Heart valve prostheses in children with reference to 95 cases]. Over a 10 year period, 95 children aged 15 years and less underwent replacement of one or several of their heart valves, usually by a Starr-Edwards ball prosthesis. The predominant pathology was rheumatic heart disease and the most commonly affected valve was the mitral. Severe symptomatology, heart failure, cardiomegaly and high wedged-capillary and pulmonary arterial pressures were practically constant findings. Operative mortality was low (3.2%) and the long-term mortality was 10 patients. With an average follow-up of 40 months, results were excellent in the great majority of patients, with complete regression of symptoms, cardiomegaly and high capillary and pulmonary arterial pressures. Anticoagulant therapy was not systematic and only half the series were so treated. Thromboembolic complications were rare, 5.5% patients, but only affected those without anticoagulant therapy. The problems of evolving rheumatic disease and, above all, of tricuspid incompetence, the persistence of which after surgery on the mitral valve seems to be a sign of advanced myocardial damage, are discussed."} {"id": "PMID:160221", "title": "[New data on the ambiguous nature of the effects of exogamy on human growth processes].", "content": "Growth peculiarities were followed in children of pre-school and school age (Ukrainians from Dnepropetrovsk Region, Kumyks, and Avartses from Dagestan, Tadjiks, Usbeks and Kirghizes from Middle Asia) with a special reference to exogamy estimated both by the presence or absence of relationship between their parents and by the distance between their birthplaces denoted as 0, I and II degrees of exogamy (DE). In every ethnic groups investigated with transition from 0 to DE to 1 DE increase in growth activity was noted. Transition from 1 DE to 11 DE in Ukrainians, Kirghizes and Usbeks was accompanied by some decrease in growth activity, while in Kumyks and Avartses it remains at the same level. The differences noted could be explained by various demographic conditions in population of the regions studied. As the studies demonstrated in Ukrainian children, activation in growth processes in the population with 1 DE is followed by the appearance of some peculiarities in dermatoglyphics and odontoglyphics which were absent in children with 0 DE and 11 DE. The data obtained demonstrate a certain role of genetic factors in developmental acceleration displaying at a moderate degree of exogamy.", "contents": "[New data on the ambiguous nature of the effects of exogamy on human growth processes]. Growth peculiarities were followed in children of pre-school and school age (Ukrainians from Dnepropetrovsk Region, Kumyks, and Avartses from Dagestan, Tadjiks, Usbeks and Kirghizes from Middle Asia) with a special reference to exogamy estimated both by the presence or absence of relationship between their parents and by the distance between their birthplaces denoted as 0, I and II degrees of exogamy (DE). In every ethnic groups investigated with transition from 0 to DE to 1 DE increase in growth activity was noted. Transition from 1 DE to 11 DE in Ukrainians, Kirghizes and Usbeks was accompanied by some decrease in growth activity, while in Kumyks and Avartses it remains at the same level. The differences noted could be explained by various demographic conditions in population of the regions studied. As the studies demonstrated in Ukrainian children, activation in growth processes in the population with 1 DE is followed by the appearance of some peculiarities in dermatoglyphics and odontoglyphics which were absent in children with 0 DE and 11 DE. The data obtained demonstrate a certain role of genetic factors in developmental acceleration displaying at a moderate degree of exogamy."} {"id": "PMID:160218", "title": "[Radiology in the diagnosis of Goodpasture's syndrome].", "content": "Radiology has an important part to play in Goodpasture's syndrome. The radio-sympatomatological value of lung changes are clarified and subdivided into primary, secondary and mixed, and mention made of the possible significance of cardiomegaly, where present. Special attention is paid to the importance of radiological exploration of the kidneys for the recognition of changes whose concomitance with lung changes may suggest diagnosis of Goodpasture's syndrome.", "contents": "[Radiology in the diagnosis of Goodpasture's syndrome]. Radiology has an important part to play in Goodpasture's syndrome. The radio-sympatomatological value of lung changes are clarified and subdivided into primary, secondary and mixed, and mention made of the possible significance of cardiomegaly, where present. Special attention is paid to the importance of radiological exploration of the kidneys for the recognition of changes whose concomitance with lung changes may suggest diagnosis of Goodpasture's syndrome."} {"id": "PMID:160222", "title": "Calcium ion-dependent adenosine triphosphatase activity and plasma-membrane phosphorylation in the human neutrophil.", "content": "A plasma-membrane fraction was isolated from a post-nuclear extract of human neutrophils by centrifugation through a linear sucrose density gradient. This fraction exhibited a Ca2+-dependent adenosine triphosphatase (ATPase) activity that could be differentiated from mitochondrial or myosin ATPase and from plasma-membrane Mg2+-dependent ATPase. When assayed in the presence of [gamma-32P]ATP, the Ca2+-dependent ATPase reaction resulted in the formation of an acid-resistant hydroxylamine-sensitive bond between the gamma-[32P] phosphate group and a membrane protein subunit with an apparent mol.wt. of 135000. Half-maximal activating effect of Ca2+ was found at 82nM and 0.18 microM for the ATPase and the formation of the 32P-membrane complex respectively. Generation of the phosphorylated product attained the steady state at 0 degrees C by about 30s, and was rapidly reversed by ADP. These results suggest that the Ca2+-activated ATPase reaction occurs through the formation of a phosphoprotein intermediate, similar to that described for some Ca2+-dependent ATPase enzymes associated with Ca2+ transport. The possibility thus exists that the neutrophil Ca2+-dependent ATPase catalyses a process of Ca2+ extrusion from the cell, thereby participating in the regulation of several Ca2+-dependent neutrophil functions.", "contents": "Calcium ion-dependent adenosine triphosphatase activity and plasma-membrane phosphorylation in the human neutrophil. A plasma-membrane fraction was isolated from a post-nuclear extract of human neutrophils by centrifugation through a linear sucrose density gradient. This fraction exhibited a Ca2+-dependent adenosine triphosphatase (ATPase) activity that could be differentiated from mitochondrial or myosin ATPase and from plasma-membrane Mg2+-dependent ATPase. When assayed in the presence of [gamma-32P]ATP, the Ca2+-dependent ATPase reaction resulted in the formation of an acid-resistant hydroxylamine-sensitive bond between the gamma-[32P] phosphate group and a membrane protein subunit with an apparent mol.wt. of 135000. Half-maximal activating effect of Ca2+ was found at 82nM and 0.18 microM for the ATPase and the formation of the 32P-membrane complex respectively. Generation of the phosphorylated product attained the steady state at 0 degrees C by about 30s, and was rapidly reversed by ADP. These results suggest that the Ca2+-activated ATPase reaction occurs through the formation of a phosphoprotein intermediate, similar to that described for some Ca2+-dependent ATPase enzymes associated with Ca2+ transport. The possibility thus exists that the neutrophil Ca2+-dependent ATPase catalyses a process of Ca2+ extrusion from the cell, thereby participating in the regulation of several Ca2+-dependent neutrophil functions."} {"id": "PMID:160223", "title": "Glycogen synthesis by hepatocytes from diabetic rats.", "content": "Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals.", "contents": "Glycogen synthesis by hepatocytes from diabetic rats. Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals."} {"id": "PMID:160231", "title": "Analysis of vasodilatory action of a new nitroester agent, 2-nicotinamidoethyl nitrate (SG-75).", "content": "Effects of 2-nicotinamidoethyl nitrate (SG-75) on cardiovascular system were investigated using whole animals and isolated vascular smooth muscles of dogs and rabbits. In dogs in vivo SG-75 i.v. produced dose-dependent falls in systemic blood pressure (SBP) concomitant with increases in heart rate (HR). Hypotension by SG-75 was not affected by propranolol and atropine but slightly inhibited by diphenhydramine. Norepinephrine (NE) dose-dependently increased SBP, and SG-75 could not affect these effects of NE. In dog coronary arterial strips contracted with potassium, SG-75 produced a dose-dependent relaxation of these strips. These effects of SG-75 were not affected by propranolol and atropine, but slightly inhibited by diphenhydramine. NE dose-dependently increased the tension of helical strips prepared from rabbit femoral artery, rabbit aorta and dog coronary artery. But SG-75 could not alter these effects of NE. The results suggest that SG-75 may have not an adrenergic beta-receptor stimulating action, a muscarinic action and an adrenergic alpha-receptor blocking action, but an inconsiderable histamine-like action. Probably, a main action of SG-75 may be a nitroglycerin-like action.", "contents": "Analysis of vasodilatory action of a new nitroester agent, 2-nicotinamidoethyl nitrate (SG-75). Effects of 2-nicotinamidoethyl nitrate (SG-75) on cardiovascular system were investigated using whole animals and isolated vascular smooth muscles of dogs and rabbits. In dogs in vivo SG-75 i.v. produced dose-dependent falls in systemic blood pressure (SBP) concomitant with increases in heart rate (HR). Hypotension by SG-75 was not affected by propranolol and atropine but slightly inhibited by diphenhydramine. Norepinephrine (NE) dose-dependently increased SBP, and SG-75 could not affect these effects of NE. In dog coronary arterial strips contracted with potassium, SG-75 produced a dose-dependent relaxation of these strips. These effects of SG-75 were not affected by propranolol and atropine, but slightly inhibited by diphenhydramine. NE dose-dependently increased the tension of helical strips prepared from rabbit femoral artery, rabbit aorta and dog coronary artery. But SG-75 could not alter these effects of NE. The results suggest that SG-75 may have not an adrenergic beta-receptor stimulating action, a muscarinic action and an adrenergic alpha-receptor blocking action, but an inconsiderable histamine-like action. Probably, a main action of SG-75 may be a nitroglycerin-like action."} {"id": "PMID:160237", "title": "Effect of Diazepam at the neuromuscular junction. A clinical study.", "content": "In patients undergoing surgery under general anaesthesia diazepam 0.16 mg kg-1 had no effect on mechanical twitch height of the adductor pollicis muscle of the thumb when the ulnar nerve was stimulated at the wrist. The muscle responses were evoked by single, repeated supramaximal stimuli at 0.2 Hz and \"train-of-four\" stimulation at 2 Hz for 2 s. Diazepam 0.16 mg kg-1 had no effect on the depth or recovery of neuromuscular blockade produced by suxamethonium, tubocurarine, pancuronium, fazadinium or alcuronium.", "contents": "Effect of Diazepam at the neuromuscular junction. A clinical study. In patients undergoing surgery under general anaesthesia diazepam 0.16 mg kg-1 had no effect on mechanical twitch height of the adductor pollicis muscle of the thumb when the ulnar nerve was stimulated at the wrist. The muscle responses were evoked by single, repeated supramaximal stimuli at 0.2 Hz and \"train-of-four\" stimulation at 2 Hz for 2 s. Diazepam 0.16 mg kg-1 had no effect on the depth or recovery of neuromuscular blockade produced by suxamethonium, tubocurarine, pancuronium, fazadinium or alcuronium."} {"id": "PMID:160238", "title": "Regurgitation during pelvic laparoscopy.", "content": "In two of 93 fasting patients undergoing gynaecological laparoscopic procedures, there was evidence of gastric regurgitation to the pharynx. It is suggested that prophylactic measures should be taken in such patients to avoid the acid aspiration syndrome.", "contents": "Regurgitation during pelvic laparoscopy. In two of 93 fasting patients undergoing gynaecological laparoscopic procedures, there was evidence of gastric regurgitation to the pharynx. It is suggested that prophylactic measures should be taken in such patients to avoid the acid aspiration syndrome."} {"id": "PMID:160239", "title": "Impaired regulation of erythrocyte autoantibody production after splenectomy.", "content": "C3H mice were given 4 i.p. injections, eac of 2 X 10(8) WAG rat RBC, at weekly intervals. The production of erythrocyte autoantibodies elicited by the cross-reacting rat RBC was assessed using the average direct Coombs' test (DCT) score. Autoantibody production reached higher levels and persisted significantly longer in mice splenectomized 15 days before the first injection of rat RBC. This increased production of autoantibodies was not prevented by injecting each splenectomized mouse i.v. with 5 X 10(7) syngeneic spleen cells immediately after splenectomy. Similarly, splenectomy of mice already DCT+ significantly prolonged autoantibody production which was not prevented by injections of 10(8) cells prepared from the spleens removed at splenectomy. Transfer of spleen cells from mice already DCT+ to mice before the injections of rat RBC were started in the recipients caused a significant reduction in the amount of RBC autoantibodies produced. This suppression of autoantibody production was greater in unsplenectomized mice than in splenectomized mice. The results show that the spleen is involved in the regulation of these erythrocyte autoantibody responses. It is hypothesized that, in addition to the cellular component of the spleen, the splenic architecture and/or environment contributes to the regulation of autoantibody responses.", "contents": "Impaired regulation of erythrocyte autoantibody production after splenectomy. C3H mice were given 4 i.p. injections, eac of 2 X 10(8) WAG rat RBC, at weekly intervals. The production of erythrocyte autoantibodies elicited by the cross-reacting rat RBC was assessed using the average direct Coombs' test (DCT) score. Autoantibody production reached higher levels and persisted significantly longer in mice splenectomized 15 days before the first injection of rat RBC. This increased production of autoantibodies was not prevented by injecting each splenectomized mouse i.v. with 5 X 10(7) syngeneic spleen cells immediately after splenectomy. Similarly, splenectomy of mice already DCT+ significantly prolonged autoantibody production which was not prevented by injections of 10(8) cells prepared from the spleens removed at splenectomy. Transfer of spleen cells from mice already DCT+ to mice before the injections of rat RBC were started in the recipients caused a significant reduction in the amount of RBC autoantibodies produced. This suppression of autoantibody production was greater in unsplenectomized mice than in splenectomized mice. The results show that the spleen is involved in the regulation of these erythrocyte autoantibody responses. It is hypothesized that, in addition to the cellular component of the spleen, the splenic architecture and/or environment contributes to the regulation of autoantibody responses."} {"id": "PMID:160240", "title": "Thiamphenicol and lupus nephritis. II. The effects of giving the drug from weaning to NZBxOUW F1 hybrid female mice.", "content": "Thiamphenicol at the rate of 50 mg/kg/day given to female NZBxOUW F1 hybrid mice from weaning and continuing throughout life resulted in a considerable extension of lifespan, although this was less than in mice given the same drug dosage from first antinuclear antibody (ANA) positivity (Simpson, Aarons and Howie, 1979). Assessment of the changes in renal dysfunction and renal histology shows that thiamphenicol treatment did not prevent the development of immune complex glomerulonephritis although the rate of progression of the disease was slower than in untreated controls. Thiamphenicol failed to influence greatly the progressive anaemia which develops in these mice or to alter the pattern of ANA production. Although azotaemia developed in treated mice it was a terminal event. It was concluded that the action of thiamphenicol was to depress but not prevent immune complex formation possibly by impairing immunoglobulin formation although why immunofluorescent ANA formation remained unaffected is not understood.", "contents": "Thiamphenicol and lupus nephritis. II. The effects of giving the drug from weaning to NZBxOUW F1 hybrid female mice. Thiamphenicol at the rate of 50 mg/kg/day given to female NZBxOUW F1 hybrid mice from weaning and continuing throughout life resulted in a considerable extension of lifespan, although this was less than in mice given the same drug dosage from first antinuclear antibody (ANA) positivity (Simpson, Aarons and Howie, 1979). Assessment of the changes in renal dysfunction and renal histology shows that thiamphenicol treatment did not prevent the development of immune complex glomerulonephritis although the rate of progression of the disease was slower than in untreated controls. Thiamphenicol failed to influence greatly the progressive anaemia which develops in these mice or to alter the pattern of ANA production. Although azotaemia developed in treated mice it was a terminal event. It was concluded that the action of thiamphenicol was to depress but not prevent immune complex formation possibly by impairing immunoglobulin formation although why immunofluorescent ANA formation remained unaffected is not understood."} {"id": "PMID:160241", "title": "Evaluation of carcinogenic effect of mineral oil used in the processing of jute fibres.", "content": "To evaluate the carcinogenic activity of jute-batching oil (JBO), this substance was painted on the skin of ITRC mice up to 300 days. Initially hyper- and parakeratosis of the stratum corneum, acanthosis and spongiosis of the stratum Malpighii, hyperactivity of fibroblasts, and laying down of collagen fibres in the dermis were encountered at 100 days. This was followed by poor hair growth, acne formation and ulceration. As time passed, these animals partially adapted themselves to the oil-painting so that by 200 days hyperkeratosis and parakeratosis of the stratum corneum, as well as acanthosis and spongiosis of the stratum Malpighii, had almost disappeared. The ulcers healed and no more acne was visible; however, the baldness and loss of hair appendages persisted to 300 days. No carcinogenic changes in the skin or in the viscera of these mice were observed. On UV and IR spectroscopy no traces of any polycyclic aromatic hydrocarbons were found in the JBO sample. Mice, on the other hand, when painted with the known carcinogen 3,4 benzpyrene (BP), developed skin tumours, showing that the mice used in this study were not cancer-resistant. Also, when JBO was applied with BP, the time taken for tumour development in mice was shortened by about 4 weeks as compared to another group painted with the same dose of BP alone. This suggests a cancer-promoting activity which needs to be investigated further.", "contents": "Evaluation of carcinogenic effect of mineral oil used in the processing of jute fibres. To evaluate the carcinogenic activity of jute-batching oil (JBO), this substance was painted on the skin of ITRC mice up to 300 days. Initially hyper- and parakeratosis of the stratum corneum, acanthosis and spongiosis of the stratum Malpighii, hyperactivity of fibroblasts, and laying down of collagen fibres in the dermis were encountered at 100 days. This was followed by poor hair growth, acne formation and ulceration. As time passed, these animals partially adapted themselves to the oil-painting so that by 200 days hyperkeratosis and parakeratosis of the stratum corneum, as well as acanthosis and spongiosis of the stratum Malpighii, had almost disappeared. The ulcers healed and no more acne was visible; however, the baldness and loss of hair appendages persisted to 300 days. No carcinogenic changes in the skin or in the viscera of these mice were observed. On UV and IR spectroscopy no traces of any polycyclic aromatic hydrocarbons were found in the JBO sample. Mice, on the other hand, when painted with the known carcinogen 3,4 benzpyrene (BP), developed skin tumours, showing that the mice used in this study were not cancer-resistant. Also, when JBO was applied with BP, the time taken for tumour development in mice was shortened by about 4 weeks as compared to another group painted with the same dose of BP alone. This suggests a cancer-promoting activity which needs to be investigated further."} {"id": "PMID:160242", "title": "Bacterial flora of comedones.", "content": "Open comedones from thirty-eight patients with acne vulgaris on the face or back were compared for microbial flora. A total of eighty-three comedones from the face and sixty-three from the upper back were individually processed for quantitative bacterial analysis. The greatest difference between the flora of comedones at these two sites was that 44.6% of comedones from the back (compared to 9.6% from the face) harboured no aerobic cocci. The decreased prevalence of staphylococci in the lesions from the back reflects the relative absence of these organisms in isolated follicles from normal uninvolved skin of the back. The geometric mean count of anaerobes in comedones from the back was in the same range as the count found in isolated follicles in normal uninvolved skin in a previous study. This work supports the concept that the bacterial flora of comedones is an extension of the follicular flora and may be unrelated to the event of comedogenesis.", "contents": "Bacterial flora of comedones. Open comedones from thirty-eight patients with acne vulgaris on the face or back were compared for microbial flora. A total of eighty-three comedones from the face and sixty-three from the upper back were individually processed for quantitative bacterial analysis. The greatest difference between the flora of comedones at these two sites was that 44.6% of comedones from the back (compared to 9.6% from the face) harboured no aerobic cocci. The decreased prevalence of staphylococci in the lesions from the back reflects the relative absence of these organisms in isolated follicles from normal uninvolved skin of the back. The geometric mean count of anaerobes in comedones from the back was in the same range as the count found in isolated follicles in normal uninvolved skin in a previous study. This work supports the concept that the bacterial flora of comedones is an extension of the follicular flora and may be unrelated to the event of comedogenesis."} {"id": "PMID:160243", "title": "Pretibial myxoedema: stimulation of mucopolysaccharide production of fibroblasts by serum.", "content": "We have shown that sera from normal individuals and from patients with pretibial myxoedema contain a factor which simulates mucopolysaccharide biosynthesis in normal human skin fibroblasts cultured in vitro. This factor was present in larger amounts in sera of patients with pretibial myxoedema. The role of growth stimulating factors in serum is reviewed and a hypothesis is put forward that the fibroblast stimulating factor is somatomedin and that its presence in increased amounts in thyroid disease may lead to pretibial myxoedema.", "contents": "Pretibial myxoedema: stimulation of mucopolysaccharide production of fibroblasts by serum. We have shown that sera from normal individuals and from patients with pretibial myxoedema contain a factor which simulates mucopolysaccharide biosynthesis in normal human skin fibroblasts cultured in vitro. This factor was present in larger amounts in sera of patients with pretibial myxoedema. The role of growth stimulating factors in serum is reviewed and a hypothesis is put forward that the fibroblast stimulating factor is somatomedin and that its presence in increased amounts in thyroid disease may lead to pretibial myxoedema."} {"id": "PMID:160244", "title": "Warfarin skin necrosis. The role of factor VII.", "content": "Necrosis of cutaneous and subcutaneous tissue is a rare complication of therapy of with oral anticoagulants, and is related to the use of loading-dose regimes. Three cases are reported, and demonstrate that the principal histopathological feature is thrombosis within the subcutaneous vasculature. The effect of large doses of anticoagulant on the levels of the vitamin K dependent clotting factors provides a satisfactory model for the temporal sequence of events in this syndrome. The occurrence of intravascular thrombosis with low or absent levels of Factor VII indicates that the intrinsic clotting system is of primary importance in venous thrombosis. This complication of anticoagulant therapy is not seen if loading-dose regimes are avoided.", "contents": "Warfarin skin necrosis. The role of factor VII. Necrosis of cutaneous and subcutaneous tissue is a rare complication of therapy of with oral anticoagulants, and is related to the use of loading-dose regimes. Three cases are reported, and demonstrate that the principal histopathological feature is thrombosis within the subcutaneous vasculature. The effect of large doses of anticoagulant on the levels of the vitamin K dependent clotting factors provides a satisfactory model for the temporal sequence of events in this syndrome. The occurrence of intravascular thrombosis with low or absent levels of Factor VII indicates that the intrinsic clotting system is of primary importance in venous thrombosis. This complication of anticoagulant therapy is not seen if loading-dose regimes are avoided."} {"id": "PMID:160245", "title": "Regulatory properties of single-headed fragments of scallop myosin.", "content": "Calcium control was studied in single-headed myosin and subfragment-1 (S1) preparations obtained by papain digestion of scallop myosin. Single-headed myosin, containing light chains in stoichiometric amounts, was calcium regulated; in contrast, the actin-activated Mg-ATPase of all S1 species lacked calcium sensitivity. Both regulatory and essential light chains were retained by S1 and single-headed myosin preparations provided divalent cations were present during papain digestion, although a peptide amounting to 10% of the mass was removed from regulatory light chains. The modified regulatory light chain retained its ability to confer calcium binding and restore calcium sensitivity to the ATPase of desensitized myofibrils. Regulatory light chains protected the essential light chains from fragmentation by papain. S1 bound regulatory light chains with a uniformly high affinity and appeared to consist of a single species. The results demonstrate that head to head interactions are not obligatory for calcium control, although they may occur in the intact myosin molecule, and suggest a role for the subfragment-2 region in calcium regulation of myosin.", "contents": "Regulatory properties of single-headed fragments of scallop myosin. Calcium control was studied in single-headed myosin and subfragment-1 (S1) preparations obtained by papain digestion of scallop myosin. Single-headed myosin, containing light chains in stoichiometric amounts, was calcium regulated; in contrast, the actin-activated Mg-ATPase of all S1 species lacked calcium sensitivity. Both regulatory and essential light chains were retained by S1 and single-headed myosin preparations provided divalent cations were present during papain digestion, although a peptide amounting to 10% of the mass was removed from regulatory light chains. The modified regulatory light chain retained its ability to confer calcium binding and restore calcium sensitivity to the ATPase of desensitized myofibrils. Regulatory light chains protected the essential light chains from fragmentation by papain. S1 bound regulatory light chains with a uniformly high affinity and appeared to consist of a single species. The results demonstrate that head to head interactions are not obligatory for calcium control, although they may occur in the intact myosin molecule, and suggest a role for the subfragment-2 region in calcium regulation of myosin."} {"id": "PMID:160247", "title": "Protein-lipid interactions. A nuclear magnetic resonance study of sarcoplasmic reticulum Ca2,Mg2+-ATPase, lipophilin, and proteolipid apoprotein-lecithin systems and a comparison with the effects of cholesterol.", "content": "Deuterium Fourier transform nuclear magnetic resonance (NMR) spectra at 34 MHz (corresponding to a magnetic field strength of 5.2 T) have been obtained of a variety of protein-lipid systems containing specifically deuterated phospholipids. The following systems were investigated as a function of temperature: sarcoplasmic reticulum ATPase (ATP phosphohydrolase, EC 3.6.1.3) complexed with 1-myristoyl-2-(14,14,14-trideuteriomyristoyl)-sn-glycero-3-phosphocholine (DMPC-d3) or 1,2-bis(16,16,16-trideuteriopalmitoyl)-sn-glycero-3-phosphocholine (DPPC-k6); human brain lipophilin complexed with DPPC-d6 or 1,2-bis(6,6-dideuteriopalmitoyl)-sn-glycero-3-phosphocholine (DPPC-6,6-d4); beef brain myelin proteolipid apoprotein (PLA) reconstituted with DMPC labeled as CD2 (or CD3) at one or more of positions 3, 4, 6, 8, 10, 12, or 14 of the sn-2 chain. For purposes of comparison, spectra were also obtained for bilayers containing cholesterol (CHOL). The results show that proteins either disorder or have little effect on hydrocarbon chain order in membranes above the gel to liquid-crystal phase transition temperature (Tc) of the pure lipids. Cholesterol, however, causes a very large ordering of the hydrocarbon chains above Tc, but both cholesterol and protein prevent chain crystallization (by effectively disordering chain packing) immediately below Tc. No evidence for any ordered \"boundary lipid\" in association with protein was found above Tc, perhaps due to the rough nature of protein surfaces. Above Tc, exchange between free bilayer and protein associated lipid is fast on the time scale of the deuterium NMR experiment (greater than or similar to 10(3) s-1). We have also obtained proton-decoupled phosphorus-31 nuclear magnetic resonance spectra at 60.7 MHz (corresponding to a magnetic field strength of 3.5 T) of DMPC, DMPC-AT-Pase, and DMPC-CHOL complexes. The results indicate that ATPase and CHOL CAUSE SMALL DECREASES IN 31P chemical shielding anisotropies but that in addition ATPase causes a four- to fivefold increase in 31P spin-lattice and Carr-Purcell spin-spin relaxation rates, suggesting the possibility of polar group protein-lipid interaction leading to increased correlation times in the region of the lipid phosphate head group.", "contents": "Protein-lipid interactions. A nuclear magnetic resonance study of sarcoplasmic reticulum Ca2,Mg2+-ATPase, lipophilin, and proteolipid apoprotein-lecithin systems and a comparison with the effects of cholesterol. Deuterium Fourier transform nuclear magnetic resonance (NMR) spectra at 34 MHz (corresponding to a magnetic field strength of 5.2 T) have been obtained of a variety of protein-lipid systems containing specifically deuterated phospholipids. The following systems were investigated as a function of temperature: sarcoplasmic reticulum ATPase (ATP phosphohydrolase, EC 3.6.1.3) complexed with 1-myristoyl-2-(14,14,14-trideuteriomyristoyl)-sn-glycero-3-phosphocholine (DMPC-d3) or 1,2-bis(16,16,16-trideuteriopalmitoyl)-sn-glycero-3-phosphocholine (DPPC-k6); human brain lipophilin complexed with DPPC-d6 or 1,2-bis(6,6-dideuteriopalmitoyl)-sn-glycero-3-phosphocholine (DPPC-6,6-d4); beef brain myelin proteolipid apoprotein (PLA) reconstituted with DMPC labeled as CD2 (or CD3) at one or more of positions 3, 4, 6, 8, 10, 12, or 14 of the sn-2 chain. For purposes of comparison, spectra were also obtained for bilayers containing cholesterol (CHOL). The results show that proteins either disorder or have little effect on hydrocarbon chain order in membranes above the gel to liquid-crystal phase transition temperature (Tc) of the pure lipids. Cholesterol, however, causes a very large ordering of the hydrocarbon chains above Tc, but both cholesterol and protein prevent chain crystallization (by effectively disordering chain packing) immediately below Tc. No evidence for any ordered \"boundary lipid\" in association with protein was found above Tc, perhaps due to the rough nature of protein surfaces. Above Tc, exchange between free bilayer and protein associated lipid is fast on the time scale of the deuterium NMR experiment (greater than or similar to 10(3) s-1). We have also obtained proton-decoupled phosphorus-31 nuclear magnetic resonance spectra at 60.7 MHz (corresponding to a magnetic field strength of 3.5 T) of DMPC, DMPC-AT-Pase, and DMPC-CHOL complexes. The results indicate that ATPase and CHOL CAUSE SMALL DECREASES IN 31P chemical shielding anisotropies but that in addition ATPase causes a four- to fivefold increase in 31P spin-lattice and Carr-Purcell spin-spin relaxation rates, suggesting the possibility of polar group protein-lipid interaction leading to increased correlation times in the region of the lipid phosphate head group."} {"id": "PMID:160248", "title": "Comparative analysis of chicken atrial and ventricular myosins.", "content": "1. Structural and enzymic properties of myosins from atrial and ventricular cardiac muscle of the chicken were investigated and compared with myosins from the fast skeletal pectoralis and the slow skeletal anterior latissimus dorsi muscle. 2. The Ca2+-ATPase activity, both in function of pH and [K+], of atrial myosin closely resembled that of the fast pectoralis myosin, whereas the enzymic properties of ventricular myosin were similar to those of slow skeletal myosin. 3. By sodium dodecyl sulphate polyacrylamide gel electrophoresis on gradient gel and two-dimensional electrophoresis, involving isoelectric focusing in the first dimension and SDS gel electrophoresis in the second dimension, no difference could be demonstrated in the light-chain pattern of atrial and ventricular myosin. Complete identity was also found between anterior latissimus dorsi and cardiac light chains. 4. Electrophoretic analysis of soluble peptides released by tryptic digestion of myosin and electron microscopic study of light meromyosin paracrystals showed significant differences between the heavy chains of atrial and ventricular myosins, as well as between the heavy chains of cardiac and skeletal myosins. 5. The results confirm previous immunochemical findings and provide direct biochemical evidence for the existence of a new, unique type of myosin in the chicken atrial tissue.", "contents": "Comparative analysis of chicken atrial and ventricular myosins. 1. Structural and enzymic properties of myosins from atrial and ventricular cardiac muscle of the chicken were investigated and compared with myosins from the fast skeletal pectoralis and the slow skeletal anterior latissimus dorsi muscle. 2. The Ca2+-ATPase activity, both in function of pH and [K+], of atrial myosin closely resembled that of the fast pectoralis myosin, whereas the enzymic properties of ventricular myosin were similar to those of slow skeletal myosin. 3. By sodium dodecyl sulphate polyacrylamide gel electrophoresis on gradient gel and two-dimensional electrophoresis, involving isoelectric focusing in the first dimension and SDS gel electrophoresis in the second dimension, no difference could be demonstrated in the light-chain pattern of atrial and ventricular myosin. Complete identity was also found between anterior latissimus dorsi and cardiac light chains. 4. Electrophoretic analysis of soluble peptides released by tryptic digestion of myosin and electron microscopic study of light meromyosin paracrystals showed significant differences between the heavy chains of atrial and ventricular myosins, as well as between the heavy chains of cardiac and skeletal myosins. 5. The results confirm previous immunochemical findings and provide direct biochemical evidence for the existence of a new, unique type of myosin in the chicken atrial tissue."} {"id": "PMID:160249", "title": "Effect of cardiac and skeletal tropomyosin on Mg2+-actomyosin ATPase.", "content": "Tropomyosin, one of the proteins regulating the sarcomere, was prepared from pig heart and rabbit skeletal muscles. The effect of these two different tropomyosins was studied between 0.5 and 10 mM of Mg2+ at a constant ATP concentration (1 mM) on reconstituted actomyosin prepared from pig heart myosin and rabbit skeletal actin. Cardiac and skeletal tropomyosin both activated the ATPase at low Mg2+ concentrations and inhibited it above 3 mM. The pig heart and rabbit skeletal tropomyosins which contain two isomers, alpha alpha and alpha beta, respectively has very similar effects on actomyosin ATPase.", "contents": "Effect of cardiac and skeletal tropomyosin on Mg2+-actomyosin ATPase. Tropomyosin, one of the proteins regulating the sarcomere, was prepared from pig heart and rabbit skeletal muscles. The effect of these two different tropomyosins was studied between 0.5 and 10 mM of Mg2+ at a constant ATP concentration (1 mM) on reconstituted actomyosin prepared from pig heart myosin and rabbit skeletal actin. Cardiac and skeletal tropomyosin both activated the ATPase at low Mg2+ concentrations and inhibited it above 3 mM. The pig heart and rabbit skeletal tropomyosins which contain two isomers, alpha alpha and alpha beta, respectively has very similar effects on actomyosin ATPase."} {"id": "PMID:160253", "title": "[Suppression of delayed hypersensitivity in mice receiving a massive dose of xenogeneic erythrocytes].", "content": "The injection of 6x109 sheep red blood cells to mice suppresses delayed-type hypersensitivity (DTH) in situ and activates spleen cells which prevent sensitization of recipients. Preliminary thymectomy of donors and the treatment of cell suspensions with anti-T-globulin abolish suppression of DTH. Pretreatment of mice with low doses of cyclophosphamide (CY) enhances antibody formation and DTH. Higher doses of CY increase the DTH reaction but inhibit antibody formation. The data obtained allow to conclude that suppression of DTH is due to the activity of short-living, intensively proliferating cells of thymic origin and possibly to B cells.", "contents": "[Suppression of delayed hypersensitivity in mice receiving a massive dose of xenogeneic erythrocytes]. The injection of 6x109 sheep red blood cells to mice suppresses delayed-type hypersensitivity (DTH) in situ and activates spleen cells which prevent sensitization of recipients. Preliminary thymectomy of donors and the treatment of cell suspensions with anti-T-globulin abolish suppression of DTH. Pretreatment of mice with low doses of cyclophosphamide (CY) enhances antibody formation and DTH. Higher doses of CY increase the DTH reaction but inhibit antibody formation. The data obtained allow to conclude that suppression of DTH is due to the activity of short-living, intensively proliferating cells of thymic origin and possibly to B cells."} {"id": "PMID:160254", "title": "[Functional morphology of the submandibular salivary glands of white rats during aging involution].", "content": "Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.", "contents": "[Functional morphology of the submandibular salivary glands of white rats during aging involution]. Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function."} {"id": "PMID:160255", "title": "[Interaction between actin like protein of the brain and isolated synaptic vesicles].", "content": "It was shown that Mg-ATP increased light diffusion in the suspension of synaptic vesicles (SV) of the rat brain in the presence of actinolike protein (ALP) of the bovine brain (the superprecipitation test). ALP enhanced the activity of the SV Mg-ATPase and increased endogenic moradrenaline release from the bovine hypothalamus SV, eliminated by cutochalazine B. Glycolipids (gengliosides and cerebrosides) inhibited the superprecipitation test. The results are considered from the standpoint of a contractile hypothesis on the mediator secretion.", "contents": "[Interaction between actin like protein of the brain and isolated synaptic vesicles]. It was shown that Mg-ATP increased light diffusion in the suspension of synaptic vesicles (SV) of the rat brain in the presence of actinolike protein (ALP) of the bovine brain (the superprecipitation test). ALP enhanced the activity of the SV Mg-ATPase and increased endogenic moradrenaline release from the bovine hypothalamus SV, eliminated by cutochalazine B. Glycolipids (gengliosides and cerebrosides) inhibited the superprecipitation test. The results are considered from the standpoint of a contractile hypothesis on the mediator secretion."} {"id": "PMID:160256", "title": "[Superficial origin of erythrocytic chalone in polycythemia in vitro].", "content": "It was shown in the culture of rat bone marrow cells in experimental polycythemia that the chalone activity of erythrocytic chalone considerably drops in the presence of phytohemagglutinin (PHA). The chalone inhibits the agglutinating activity of PHA with respect to bone marrow cells. Absorption of the chalone on the immobilized PHA leads to disappearance from it and of PAS-positive bands recorded electrophoretically and to a strong decrease in PAS-negative band intensity. Experiments with preliminary incubation of rat red cells before preparation of the chalone suggest that in the course of its preparation two polypeptides one of which is PAS-positive are released into the medium. It is suggested that the chalone includes superficial membrane proteins of red cells, possibly, in the form of a combination of PAS-positive and PAS-negative bands. Potential mechanisms of chalone release from the surface of cells and features of their action on the cells are discussed.", "contents": "[Superficial origin of erythrocytic chalone in polycythemia in vitro]. It was shown in the culture of rat bone marrow cells in experimental polycythemia that the chalone activity of erythrocytic chalone considerably drops in the presence of phytohemagglutinin (PHA). The chalone inhibits the agglutinating activity of PHA with respect to bone marrow cells. Absorption of the chalone on the immobilized PHA leads to disappearance from it and of PAS-positive bands recorded electrophoretically and to a strong decrease in PAS-negative band intensity. Experiments with preliminary incubation of rat red cells before preparation of the chalone suggest that in the course of its preparation two polypeptides one of which is PAS-positive are released into the medium. It is suggested that the chalone includes superficial membrane proteins of red cells, possibly, in the form of a combination of PAS-positive and PAS-negative bands. Potential mechanisms of chalone release from the surface of cells and features of their action on the cells are discussed."} {"id": "PMID:160257", "title": "[Increased ATP-hydrolase activity of the brain mitochondria under the effect of aminazine (electron cytochemical study)].", "content": "The localization of Mg-stimulated ATPase activity was determined in the sensomotor cortex mitochondria of Wag rats after aminazin administration (15 mg/kg). Apart from normal mitochondria containing no reaction product, a number of altered mitochondria with different localization in them of the ATPase reaction product were recorded. The intact animals showed no sediment in the mitochondria. It is suggested that aminazin-induced increase in ATP-hydrolase activity is caused by two factors: neuroleptic-induced decrease in glycolytic and oxidative cell activity and increased permeability of mitochondrial membranes.", "contents": "[Increased ATP-hydrolase activity of the brain mitochondria under the effect of aminazine (electron cytochemical study)]. The localization of Mg-stimulated ATPase activity was determined in the sensomotor cortex mitochondria of Wag rats after aminazin administration (15 mg/kg). Apart from normal mitochondria containing no reaction product, a number of altered mitochondria with different localization in them of the ATPase reaction product were recorded. The intact animals showed no sediment in the mitochondria. It is suggested that aminazin-induced increase in ATP-hydrolase activity is caused by two factors: neuroleptic-induced decrease in glycolytic and oxidative cell activity and increased permeability of mitochondrial membranes."} {"id": "PMID:160264", "title": "The early diagnosis of ectopic pregnancy.", "content": "In a survey of 235 consecutive cases of ectopic pregnancy it was found that over 50 per cent were incorrectly diagnosed by the general practitioner and 36 per cent by a hospital doctor. Ten per cent of patients were sent home before the diagnosis was made. Over 30 per cent of patients were sent to general surgical wards and these patients had different characteristics from those sent to gynaecological wards. High risk patients can be identified from their past history. The increasing use of the laparoscope has been associated with earlier detection of ectopic pregnancy before the stage of rupture.", "contents": "The early diagnosis of ectopic pregnancy. In a survey of 235 consecutive cases of ectopic pregnancy it was found that over 50 per cent were incorrectly diagnosed by the general practitioner and 36 per cent by a hospital doctor. Ten per cent of patients were sent home before the diagnosis was made. Over 30 per cent of patients were sent to general surgical wards and these patients had different characteristics from those sent to gynaecological wards. High risk patients can be identified from their past history. The increasing use of the laparoscope has been associated with earlier detection of ectopic pregnancy before the stage of rupture."} {"id": "PMID:160265", "title": "The effect of uraemia upon wound healing: an experimental study.", "content": "Acute uraemia was induced in rats by performing a 70 per cent nephrectomy. Uraemia was shown to delay the healing of intestinal anastomoses and abdominal wounds in rats as judged by bursting strength tests. Cellular proliferation was depressed at wound edges but there was no reduction in the total amount of hydroxyproline present in the wounds. Fibroblast growth in tissue culture was affected by the addition both of uraemic plasma and of urea solution to the culture medium. The possible causes of these effects are discussed.", "contents": "The effect of uraemia upon wound healing: an experimental study. Acute uraemia was induced in rats by performing a 70 per cent nephrectomy. Uraemia was shown to delay the healing of intestinal anastomoses and abdominal wounds in rats as judged by bursting strength tests. Cellular proliferation was depressed at wound edges but there was no reduction in the total amount of hydroxyproline present in the wounds. Fibroblast growth in tissue culture was affected by the addition both of uraemic plasma and of urea solution to the culture medium. The possible causes of these effects are discussed."} {"id": "PMID:160266", "title": "Controlled trial of mobilisation and manipulation for low back pain: hospital patients.", "content": "Ninety-four patients with non-specific lumbar pain referred to hospital rheumatology and orthopaedic clinics participated in a double-blind controlled trial comparing mobilisation and manipulation with placebo physiotherapy. Results were assessed immediately after the tratment course, two months later, and at one year. Many patients showed improvement, but in contrast to a study on general-practitioner patients with nonspecific back pain no definite advantage could be associated with mobilisation and manipulation. The benefits of mobilisation and manipulation for low back pain are probably restricted to hastening recovery in patients likely rapidly to improve spontaneously. Hence patients whose severity and duration of symptoms warrant specialist referral are less likely to benefit from the technique.", "contents": "Controlled trial of mobilisation and manipulation for low back pain: hospital patients. Ninety-four patients with non-specific lumbar pain referred to hospital rheumatology and orthopaedic clinics participated in a double-blind controlled trial comparing mobilisation and manipulation with placebo physiotherapy. Results were assessed immediately after the tratment course, two months later, and at one year. Many patients showed improvement, but in contrast to a study on general-practitioner patients with nonspecific back pain no definite advantage could be associated with mobilisation and manipulation. The benefits of mobilisation and manipulation for low back pain are probably restricted to hastening recovery in patients likely rapidly to improve spontaneously. Hence patients whose severity and duration of symptoms warrant specialist referral are less likely to benefit from the technique."} {"id": "PMID:160269", "title": "[Demonstration by immunofluorescence of somatostatin cells in the islets of Langerhans in 3 species of monkeys].", "content": "Indirect immunofluorescence technique with anti-somatostatin serum has allowed us to detect somatostatin containing cells in the Langerhans' islets of three species of monkeys (Macacus irus, Papio hamadryas, Cercopithecus aethiops). These cells are in close relationship with another cells, but occupy a more central position in the islets. Thus, the distribution of somatostatin-containing cells in the monkey's endocrine pancreas has not a similar pattern as in rodent's pancreas; they have a comparable topography as in the human islets but these cells are always more elongated than in the human islets. Only slight morphological differences are observed in the three species of monkeys.", "contents": "[Demonstration by immunofluorescence of somatostatin cells in the islets of Langerhans in 3 species of monkeys]. Indirect immunofluorescence technique with anti-somatostatin serum has allowed us to detect somatostatin containing cells in the Langerhans' islets of three species of monkeys (Macacus irus, Papio hamadryas, Cercopithecus aethiops). These cells are in close relationship with another cells, but occupy a more central position in the islets. Thus, the distribution of somatostatin-containing cells in the monkey's endocrine pancreas has not a similar pattern as in rodent's pancreas; they have a comparable topography as in the human islets but these cells are always more elongated than in the human islets. Only slight morphological differences are observed in the three species of monkeys."} {"id": "PMID:160270", "title": "[In vitro anti-yeast activity of 1- and 2-propanols. Effect of the addition of polyethylene glycol 400].", "content": "The in vitro development of Candida albicans is inhibited in presence of 1-propanol and 2-propanol at minimum doses determined in the present work. For these inhibiting doses, associations with 400 polyethylene glycol which generally enhances yeast filamentation proved that this polyol is no longer able to maintain cellular development.", "contents": "[In vitro anti-yeast activity of 1- and 2-propanols. Effect of the addition of polyethylene glycol 400]. The in vitro development of Candida albicans is inhibited in presence of 1-propanol and 2-propanol at minimum doses determined in the present work. For these inhibiting doses, associations with 400 polyethylene glycol which generally enhances yeast filamentation proved that this polyol is no longer able to maintain cellular development."} {"id": "PMID:160271", "title": "[Determination of the thermodynamic efficiency of isolated perfused tench heart (Tinca tinca L. Teleosteen)].", "content": "Mechanical power of tench isolated heart is obtained from values of stroke volume at constant hydrodynamic pressure. The total production of energy is measured by use of a calorimetric method and heart efficiency is calculated. The mean value of efficiency is 6.7% +/- 0.65 SEM in our experimental conditions.", "contents": "[Determination of the thermodynamic efficiency of isolated perfused tench heart (Tinca tinca L. Teleosteen)]. Mechanical power of tench isolated heart is obtained from values of stroke volume at constant hydrodynamic pressure. The total production of energy is measured by use of a calorimetric method and heart efficiency is calculated. The mean value of efficiency is 6.7% +/- 0.65 SEM in our experimental conditions."} {"id": "PMID:160272", "title": "[Effect of a tryptophan lead on the swine adrenal cortex reactivity and behavioral response to stress].", "content": "Behaviour and plasma corticosteroid levels were investigated in pigs preloaded with 50 to 200 mg/kg 1-tryptophan. The treatment did not influence reactions to frustation and had no effect on continuous avoidance responding. However the adrenal response to the stress of new environment concomitant with delivery of unavoidable shocks was decreased (fig. 1), as well as the behavioural response to a fear signal superimposed on a continuous avoidance paradigm (fig. 2). These results point out relatively specific psychotropic effects of a tryptophan load in pigs.", "contents": "[Effect of a tryptophan lead on the swine adrenal cortex reactivity and behavioral response to stress]. Behaviour and plasma corticosteroid levels were investigated in pigs preloaded with 50 to 200 mg/kg 1-tryptophan. The treatment did not influence reactions to frustation and had no effect on continuous avoidance responding. However the adrenal response to the stress of new environment concomitant with delivery of unavoidable shocks was decreased (fig. 1), as well as the behavioural response to a fear signal superimposed on a continuous avoidance paradigm (fig. 2). These results point out relatively specific psychotropic effects of a tryptophan load in pigs."} {"id": "PMID:160273", "title": "[Changes in cephalic and peripheral use of glucose and glutamine under the influence of hyperammonemia in rats].", "content": "Arterio-venous differences of glucose and glutamine were determined across the brain and across the hind limb in normal and ammonium salt infused rats, before and during an insulin tolerance test, in an attempt to study the effect of hyperammonemia on cephalic and muscular metabolism. The results demonstrate that 1) hyperammonemia reduces the hind limb uptake of glucose without affect the cephalic uptake of glucose which is lowered during hypoglycemia, 2) the reduction of the cephalic and muscular glutamine output induced by the hypoglycemia is masked in presence of an hyperammonemia. In conclusion, it may be assume that, at the concentration obtained in this study, hyperammonemia does not act directly in the pathogenesis of hepatic coma in which a decrease in cerebral glucose uptake described; on the other hand, ammonium plays an important role in the muscle metabolism.", "contents": "[Changes in cephalic and peripheral use of glucose and glutamine under the influence of hyperammonemia in rats]. Arterio-venous differences of glucose and glutamine were determined across the brain and across the hind limb in normal and ammonium salt infused rats, before and during an insulin tolerance test, in an attempt to study the effect of hyperammonemia on cephalic and muscular metabolism. The results demonstrate that 1) hyperammonemia reduces the hind limb uptake of glucose without affect the cephalic uptake of glucose which is lowered during hypoglycemia, 2) the reduction of the cephalic and muscular glutamine output induced by the hypoglycemia is masked in presence of an hyperammonemia. In conclusion, it may be assume that, at the concentration obtained in this study, hyperammonemia does not act directly in the pathogenesis of hepatic coma in which a decrease in cerebral glucose uptake described; on the other hand, ammonium plays an important role in the muscle metabolism."} {"id": "PMID:160274", "title": "[Behavioral alterations induced by post-natal exposure of the rat to lead].", "content": "The behaviour of rats exposed to various levels of lead acetate (0.5 ; 1 ; 2 and 4% in dam's diet) before weaning was recorded between 2 and 6 months of age. Higher locomotor and exploratory activities as well as better scores in active avoidance conditioning were observed in the 4% lead-treated rats. For lower doses, no behavioural alterations were recorded despite both detarded growth and increased mortality.", "contents": "[Behavioral alterations induced by post-natal exposure of the rat to lead]. The behaviour of rats exposed to various levels of lead acetate (0.5 ; 1 ; 2 and 4% in dam's diet) before weaning was recorded between 2 and 6 months of age. Higher locomotor and exploratory activities as well as better scores in active avoidance conditioning were observed in the 4% lead-treated rats. For lower doses, no behavioural alterations were recorded despite both detarded growth and increased mortality."} {"id": "PMID:160275", "title": "[Attempt at modification of the pharmacological and toxic effects of cocaine].", "content": "The increase in locomotor activity induced by cocaine (15 mg/kg, i.p.) in the mouse was antagonized by pretreatment with compounds which inhibited monoanimergic receptors such as phenoxybenzamine, chlorpromazine or methysergide. On the contrary, the lethal dose of cocaine in rats and mice was not reduced by these substances. These data suggest that monoamines are involved in mediating the motor activity of cocaine but not implicated in the toxic effect of the drug.", "contents": "[Attempt at modification of the pharmacological and toxic effects of cocaine]. The increase in locomotor activity induced by cocaine (15 mg/kg, i.p.) in the mouse was antagonized by pretreatment with compounds which inhibited monoanimergic receptors such as phenoxybenzamine, chlorpromazine or methysergide. On the contrary, the lethal dose of cocaine in rats and mice was not reduced by these substances. These data suggest that monoamines are involved in mediating the motor activity of cocaine but not implicated in the toxic effect of the drug."} {"id": "PMID:160276", "title": "[Changes in the vitro membrane potential of cancer cells induced by contact with cytotoxic lymphoid cells].", "content": "Plasma membrane potentials have been measured in a cancer cell line at different stages of growth. A chamber has been especially built for pH control of the culture medium during several hours. Individual values spread widely from 14 to 44 mV but low measurements are less frequent after 3 days of culture when the growth rate is at a peak. The same cancer line is grafted serially in syngeneic C 57 bl mice were it induces an immunological sensitization of the lymphnode cells. The effect of such cytotoxic lymphocytes on the membrane potentials of the target tumour cell has been studied after a contact (15 to 90 minutes) too short for any morphological changes to be detectable. There is a decrease in the mean values and a very significant rise in percentage of measurements below 20 mV. No such changes are observed in control experiments where na\u00efve lymphocytes are used. These results are discussed in relation to the hypothesis of an increased permeability of the plasma membrane to ions as an early event in cell mediated cytotoxicity.", "contents": "[Changes in the vitro membrane potential of cancer cells induced by contact with cytotoxic lymphoid cells]. Plasma membrane potentials have been measured in a cancer cell line at different stages of growth. A chamber has been especially built for pH control of the culture medium during several hours. Individual values spread widely from 14 to 44 mV but low measurements are less frequent after 3 days of culture when the growth rate is at a peak. The same cancer line is grafted serially in syngeneic C 57 bl mice were it induces an immunological sensitization of the lymphnode cells. The effect of such cytotoxic lymphocytes on the membrane potentials of the target tumour cell has been studied after a contact (15 to 90 minutes) too short for any morphological changes to be detectable. There is a decrease in the mean values and a very significant rise in percentage of measurements below 20 mV. No such changes are observed in control experiments where na\u00efve lymphocytes are used. These results are discussed in relation to the hypothesis of an increased permeability of the plasma membrane to ions as an early event in cell mediated cytotoxicity."} {"id": "PMID:160278", "title": "[Inhibition of carrageenan edema by carrageenan itself].", "content": "The influence of two kinin forming agents: iota carrageenan and ellagic acid, on the paw oedema induced by 48/80, an amino-liberator, or by carrageenan iota, has been studied, in the Rat. Ellagic acid and carrageenan, by intraperitoneal injection, reduce the paw oedema induced respectively by 48/80 and carrageenan itself. This inhibition depends on a non-specific \"counter-irritation\" and not on kininogen stores depletion. Ellagic acid, by intravenous injection, diminishes the oedema induced by carrageenan; swelling due to 48/80, is not affected. So kininogen activation plays some role in the inflammatory processes induced by iota carrageenan. Carrageenan by intravenous injection, suppresses his own inflammatory action but does not influence at all the similar action of 48/80. The anti-inflammatory effect of carrageenan does not exclusively depend on kininogen stores depletion.", "contents": "[Inhibition of carrageenan edema by carrageenan itself]. The influence of two kinin forming agents: iota carrageenan and ellagic acid, on the paw oedema induced by 48/80, an amino-liberator, or by carrageenan iota, has been studied, in the Rat. Ellagic acid and carrageenan, by intraperitoneal injection, reduce the paw oedema induced respectively by 48/80 and carrageenan itself. This inhibition depends on a non-specific \"counter-irritation\" and not on kininogen stores depletion. Ellagic acid, by intravenous injection, diminishes the oedema induced by carrageenan; swelling due to 48/80, is not affected. So kininogen activation plays some role in the inflammatory processes induced by iota carrageenan. Carrageenan by intravenous injection, suppresses his own inflammatory action but does not influence at all the similar action of 48/80. The anti-inflammatory effect of carrageenan does not exclusively depend on kininogen stores depletion."} {"id": "PMID:160279", "title": "[Development of estradiol, progesterone, and prostaglandins E and F2 alpha levels during pregnancy in mice].", "content": "17 beta estradiol, progesterone, prostaglandin E and prostaglandin F2 alpha were determined in the plasma of mice at different times of pregnancy. Estradiol displays a preimplantation peak on day 4. Other peaks are visible at the end of the implantation period (day 6) and on day 10. Progesterone increases when implantation begins (day 5). Prostaglandins increase at the beginning of pregnancy and decrease temporarily before implantation. Other peaks are also apparent for prostaglandin E on days 5.5 and 11.", "contents": "[Development of estradiol, progesterone, and prostaglandins E and F2 alpha levels during pregnancy in mice]. 17 beta estradiol, progesterone, prostaglandin E and prostaglandin F2 alpha were determined in the plasma of mice at different times of pregnancy. Estradiol displays a preimplantation peak on day 4. Other peaks are visible at the end of the implantation period (day 6) and on day 10. Progesterone increases when implantation begins (day 5). Prostaglandins increase at the beginning of pregnancy and decrease temporarily before implantation. Other peaks are also apparent for prostaglandin E on days 5.5 and 11."} {"id": "PMID:160280", "title": "[Kinetics of division of human and rabbit lymphocytes stimulated by phytohemagglutinin, studied by means of the bromodeoxyuridine (BUDR) technic].", "content": "The BUDR-Giemsa technique has been used to distinguish the first from later divisions for man and rabbit lymphocytes stimulated by treatment with phytohemagglutinin. At 48 hours, 99% of human lymphocytes exposed to 200 rads of X-rays are in first division whereas 45% of the rabbit lymphocytes are already in second division and 28% in third division.", "contents": "[Kinetics of division of human and rabbit lymphocytes stimulated by phytohemagglutinin, studied by means of the bromodeoxyuridine (BUDR) technic]. The BUDR-Giemsa technique has been used to distinguish the first from later divisions for man and rabbit lymphocytes stimulated by treatment with phytohemagglutinin. At 48 hours, 99% of human lymphocytes exposed to 200 rads of X-rays are in first division whereas 45% of the rabbit lymphocytes are already in second division and 28% in third division."} {"id": "PMID:160281", "title": "[Incorporation of tritiated thymidine into testicular deoxyribonucleic acid of the rat. Effect of inhibin].", "content": "tritiated thymidine is incorporated into DNA of spermatogonia type B as proved by autohistoradiography when injected in vivo three hours before the sacrifice. Maximum binding and specific activity (labelled thymidine expressed in DPM per mg DNA) are obtained in pubertal rats aged 42 days and weighting 150 g. Inhibin preparation extracted from rete testis fluid (RTF3) specifically inhibits tritiated thymidine into testicular DNA. Thus, no modification of incorporation into hepatic DNA is observed and the preparation loses its inhibitory effect when denatured by heating and trypsin digestion. Tritiated thymidine incorporation into testicular DNA is poor in normal adult rats and in pubertal hypophysectomized animals, RTF3 does not modify the thymidine incorporation in both conditions. The reasons for this lack of effect are discussed. An experimental condition of spermatogonial regeneration is obtained by testicular irradiation. Inhibin preparation inhibits the regenerative DNA synthesis.", "contents": "[Incorporation of tritiated thymidine into testicular deoxyribonucleic acid of the rat. Effect of inhibin]. tritiated thymidine is incorporated into DNA of spermatogonia type B as proved by autohistoradiography when injected in vivo three hours before the sacrifice. Maximum binding and specific activity (labelled thymidine expressed in DPM per mg DNA) are obtained in pubertal rats aged 42 days and weighting 150 g. Inhibin preparation extracted from rete testis fluid (RTF3) specifically inhibits tritiated thymidine into testicular DNA. Thus, no modification of incorporation into hepatic DNA is observed and the preparation loses its inhibitory effect when denatured by heating and trypsin digestion. Tritiated thymidine incorporation into testicular DNA is poor in normal adult rats and in pubertal hypophysectomized animals, RTF3 does not modify the thymidine incorporation in both conditions. The reasons for this lack of effect are discussed. An experimental condition of spermatogonial regeneration is obtained by testicular irradiation. Inhibin preparation inhibits the regenerative DNA synthesis."} {"id": "PMID:160282", "title": "[Effect of horizontal immersion into water at 38 degrees C on the urinary elimination of catecholamines].", "content": "The urinary excretion of noradrenaline, adrenaline and creatinine has been studied in normal young individuals during a water bath at 38 degrees C for 40 minutes. The noradrenalinuria and the ratio noradrenalinuria/creatininuria are decreased, indicating an inhibition of the vasomotor activity of the orthosympathetic system. This inhibition is related to the consequence of the external hydrostatic pressure of the water filling the intrathoracic venous reservoirs and increasing the systemic blood pressure at the sino-baroreceptor level, hyperthermia playing a very limited role.", "contents": "[Effect of horizontal immersion into water at 38 degrees C on the urinary elimination of catecholamines]. The urinary excretion of noradrenaline, adrenaline and creatinine has been studied in normal young individuals during a water bath at 38 degrees C for 40 minutes. The noradrenalinuria and the ratio noradrenalinuria/creatininuria are decreased, indicating an inhibition of the vasomotor activity of the orthosympathetic system. This inhibition is related to the consequence of the external hydrostatic pressure of the water filling the intrathoracic venous reservoirs and increasing the systemic blood pressure at the sino-baroreceptor level, hyperthermia playing a very limited role."} {"id": "PMID:160283", "title": "[Late effects of irradiation on the cerebral cortex ultrastructure of the rat].", "content": "The glial population balance is significantly disturbed by low dose X-rays even after a very short time following irradiation. The effects are able to persist for a large period of time and may possibly be involved in the onset of late radionecrosis phenomena, often noted as consequences of therapeutic irradiation in brain.", "contents": "[Late effects of irradiation on the cerebral cortex ultrastructure of the rat]. The glial population balance is significantly disturbed by low dose X-rays even after a very short time following irradiation. The effects are able to persist for a large period of time and may possibly be involved in the onset of late radionecrosis phenomena, often noted as consequences of therapeutic irradiation in brain."} {"id": "PMID:160285", "title": "Effects of reserpine and p-chlorophenylalanine on the circadian rhythm of granulated vesicles in the pinealocytes of mice.", "content": "The number of granulated vesicles in mouse pinealocytes exhibit a distinct circadian rhythm which is abolished by superior cervical ganglionectomy. Since melatonin treatment markedly effects the number of pinealocytic granulated vesicles, it was suggested that a relationship may exist between norepinephrine, melatonin, and the synthesis and/or secretion of pinealocyte granulated vesicles. The present study was undertaken in an attempt to clarify this relationship. Mice were housed in an environmental chamber under controlled lighting (12L/12D), and were treated with either reserpine, a drug which depletes serotonin and norepinephrine, or p-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis. They were sacrificed at various times over a twenty-four hour period, and granulated vesicles present in the pinealocytes were quantitated in thin cross sections through pericapillary areas. Reserpine treatment resulted in a marked increase in the number of granulated vesicles during the dark, but led to a slight decrease during the photoperiod. Treatment with p-CPA produced no significant effect. The results of this study do not support our previous theory that melatonin plays an important role in the regulation of the pinealocyte secretory process, but instead points more directly to the significant role that norepinephrine has in controlling pinealocyte secretion.", "contents": "Effects of reserpine and p-chlorophenylalanine on the circadian rhythm of granulated vesicles in the pinealocytes of mice. The number of granulated vesicles in mouse pinealocytes exhibit a distinct circadian rhythm which is abolished by superior cervical ganglionectomy. Since melatonin treatment markedly effects the number of pinealocytic granulated vesicles, it was suggested that a relationship may exist between norepinephrine, melatonin, and the synthesis and/or secretion of pinealocyte granulated vesicles. The present study was undertaken in an attempt to clarify this relationship. Mice were housed in an environmental chamber under controlled lighting (12L/12D), and were treated with either reserpine, a drug which depletes serotonin and norepinephrine, or p-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis. They were sacrificed at various times over a twenty-four hour period, and granulated vesicles present in the pinealocytes were quantitated in thin cross sections through pericapillary areas. Reserpine treatment resulted in a marked increase in the number of granulated vesicles during the dark, but led to a slight decrease during the photoperiod. Treatment with p-CPA produced no significant effect. The results of this study do not support our previous theory that melatonin plays an important role in the regulation of the pinealocyte secretory process, but instead points more directly to the significant role that norepinephrine has in controlling pinealocyte secretion."} {"id": "PMID:160286", "title": "Specificity of the bacteriophage lambda N gene product (pN): nut sequences are necessary and sufficient for antitermination by pN.", "content": "We have cloned the nutR site together with the tR1 site of bacteriophage lambda in the E. coli galactose operon to examine whether the lambda promoter sequences PR and PL are involved in the recognition specificity of the lambda N gene product (pN). We first constructed a derivative of plasmid pBR322 in which the expression of the tetracycline genes (tet) is controlled by the gal promoter (Pgal). This new plasmid contains a unique Hind III site between Pgal and tet into which the nutR and tR1 sites were introduced. The order of the relevant genetic markers in this second plasmid is Pgal-nutR-tR1-tet. Cells transformed with this plasmid express tet only if pN is provided and if the plasmid contains an intact gal promoter. Our data suggest that transcription which originates at Pgal is modified by pN at nutR, enabling it to pass through tR1 into tet. We conclude that promoters do not play a specific role in pN recognition and that nut sequences are both necessary and sufficient for pN action.", "contents": "Specificity of the bacteriophage lambda N gene product (pN): nut sequences are necessary and sufficient for antitermination by pN. We have cloned the nutR site together with the tR1 site of bacteriophage lambda in the E. coli galactose operon to examine whether the lambda promoter sequences PR and PL are involved in the recognition specificity of the lambda N gene product (pN). We first constructed a derivative of plasmid pBR322 in which the expression of the tetracycline genes (tet) is controlled by the gal promoter (Pgal). This new plasmid contains a unique Hind III site between Pgal and tet into which the nutR and tR1 sites were introduced. The order of the relevant genetic markers in this second plasmid is Pgal-nutR-tR1-tet. Cells transformed with this plasmid express tet only if pN is provided and if the plasmid contains an intact gal promoter. Our data suggest that transcription which originates at Pgal is modified by pN at nutR, enabling it to pass through tR1 into tet. We conclude that promoters do not play a specific role in pN recognition and that nut sequences are both necessary and sufficient for pN action."} {"id": "PMID:160287", "title": "Characterization of variant Neurospora crassa mitochondrial DNAs which contain tandem reiterations.", "content": "Two variant mtDNA types ((types IIa and HI-10) have been identified in individual subcultures of the extra-nuclear [poky] mutant of Neurospora crassa. Eco RI digests of type IIa mtDNA are characterized by an extra band, alpha, Mr = 1.4 Mdal, which arises from tandemly inserted reiterations of a 1.4 Mdal sequence. Restriction enzyme analysis and Southern hybridization experiments show: that the 1.4 Mdal repeats are located at the junction of Eco RI-4 and -6, that the repeats contain sequences ordinarily present in Eco RI-4 and -6, that the repeats are oriented head-to-tail and that the number of repeats per molecule (n) varies from n = 0 to n = 8, with about half of the molecules containing no repeats. The 1.4 Mdal repeats appear to be actively mained in type IIa mtDNA populations as a result of a specific alteration in mtDNA. Data are presented which suggest that this alteration may be located near small deletions and/or sequence changes in Eco RI-3 and -10, fragments almost exactly opposite the site of the repeats on the genome. The second variant, HI-10 mtDNA, arose in a heteroplasmic strain in which type IIa mtDNA was one component. The most striking feature of HI-10 mtDNA is the up to 5-fold amplification of an 18 Mdal segment extending from Eco RI-4 (the site of the 1.4 Mdal repeats) through the rRNA genes. Eco RI digests show that HI-10 possesses characteristic features of type IIa mtDNA, including the 1.4 Mdal repeats and the alteration in Eco RI-10. HI-10 mtDNA also shows a novel Eco RI fragment, beta, Mr = 2.9 Mdal. The variant Neurospora mtDNAs may be generated by mechanisms analogous to those which give rise to defective mtDNAs of yeast petite mutants. The possible consequences of defective mtDNAs in obligately aerobic organisms are discussed.", "contents": "Characterization of variant Neurospora crassa mitochondrial DNAs which contain tandem reiterations. Two variant mtDNA types ((types IIa and HI-10) have been identified in individual subcultures of the extra-nuclear [poky] mutant of Neurospora crassa. Eco RI digests of type IIa mtDNA are characterized by an extra band, alpha, Mr = 1.4 Mdal, which arises from tandemly inserted reiterations of a 1.4 Mdal sequence. Restriction enzyme analysis and Southern hybridization experiments show: that the 1.4 Mdal repeats are located at the junction of Eco RI-4 and -6, that the repeats contain sequences ordinarily present in Eco RI-4 and -6, that the repeats are oriented head-to-tail and that the number of repeats per molecule (n) varies from n = 0 to n = 8, with about half of the molecules containing no repeats. The 1.4 Mdal repeats appear to be actively mained in type IIa mtDNA populations as a result of a specific alteration in mtDNA. Data are presented which suggest that this alteration may be located near small deletions and/or sequence changes in Eco RI-3 and -10, fragments almost exactly opposite the site of the repeats on the genome. The second variant, HI-10 mtDNA, arose in a heteroplasmic strain in which type IIa mtDNA was one component. The most striking feature of HI-10 mtDNA is the up to 5-fold amplification of an 18 Mdal segment extending from Eco RI-4 (the site of the 1.4 Mdal repeats) through the rRNA genes. Eco RI digests show that HI-10 possesses characteristic features of type IIa mtDNA, including the 1.4 Mdal repeats and the alteration in Eco RI-10. HI-10 mtDNA also shows a novel Eco RI fragment, beta, Mr = 2.9 Mdal. The variant Neurospora mtDNAs may be generated by mechanisms analogous to those which give rise to defective mtDNAs of yeast petite mutants. The possible consequences of defective mtDNAs in obligately aerobic organisms are discussed."} {"id": "PMID:160292", "title": "[In vitro calcium binding by isolated brush border vesicles of rat jejunum and ileum].", "content": "A new procedure for isolation of the Rat jejunum and ileum brush border vesicles is described. Several calcium transport conditions have been established. A previous incubation with ATP induces an increased calcium binding. The role of a magnesium ATPase is discussed.", "contents": "[In vitro calcium binding by isolated brush border vesicles of rat jejunum and ileum]. A new procedure for isolation of the Rat jejunum and ileum brush border vesicles is described. Several calcium transport conditions have been established. A previous incubation with ATP induces an increased calcium binding. The role of a magnesium ATPase is discussed."} {"id": "PMID:160293", "title": "Bronchial asthma and dermatitis due to spiramycin in a chick breeder.", "content": "A case of bronchial asthma and dermatitis due to spiramycin is described in a non-atopic woman who worked as a chick breeder and handling poultry feed containing antibiotic or chemoterapic drugs including spiramycin, chlortetracycline and sulfadimethoxine. Patch tests showed a vigorous delayed reaction to spiramycin. Inhalation challenge test with the chick feed containing spiramycin reproduced symptoms of late asthmatic response (FEV1 fell by 14% and FEF25-75 by 25% within the 4th and 6th hour) with leucocytosis. No significant modification of FEV1 and FEF25-75 was observed within 24 hours after challenge with chick feeds containing other antibiotic or chemotherapeutic agents but not spiramycin. On leaving her job, the patient had no further skin reactions or bronchial asthma episodes. This case suggests that allergic reactions to a chemical product may involve both type III and IV hypersensitivity.", "contents": "Bronchial asthma and dermatitis due to spiramycin in a chick breeder. A case of bronchial asthma and dermatitis due to spiramycin is described in a non-atopic woman who worked as a chick breeder and handling poultry feed containing antibiotic or chemoterapic drugs including spiramycin, chlortetracycline and sulfadimethoxine. Patch tests showed a vigorous delayed reaction to spiramycin. Inhalation challenge test with the chick feed containing spiramycin reproduced symptoms of late asthmatic response (FEV1 fell by 14% and FEF25-75 by 25% within the 4th and 6th hour) with leucocytosis. No significant modification of FEV1 and FEF25-75 was observed within 24 hours after challenge with chick feeds containing other antibiotic or chemotherapeutic agents but not spiramycin. On leaving her job, the patient had no further skin reactions or bronchial asthma episodes. This case suggests that allergic reactions to a chemical product may involve both type III and IV hypersensitivity."} {"id": "PMID:160294", "title": "Testicular function in post pubertal male pseudohermaphroditism.", "content": "Testicular endocrine function was studied in twelve post pubertal patients with male pseudohermaphroditism and 46 XY chromosomal constitution. Patients were divided into three groups, four subjects who became feminized during puberty, five who became masculinized during puberty and three who were castrated before puberty. Serum dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstendione, testosterone, dihydrotestosterone, LH and FSH were determined by radioimmunoassay. Patients of the first group had the clinical characteristics of testicular feminization secondary to absence of the androgen receptor. One of the five patients of the second group had deficient testosterone secretion but no enzymatic defect could be demonstrated. One of the subjects castrated before puberty had a deficiency in 17,20-desmolase. Therefore, evidence of a failure of the fetal testes could be found in only two of the twelve patients studied.", "contents": "Testicular function in post pubertal male pseudohermaphroditism. Testicular endocrine function was studied in twelve post pubertal patients with male pseudohermaphroditism and 46 XY chromosomal constitution. Patients were divided into three groups, four subjects who became feminized during puberty, five who became masculinized during puberty and three who were castrated before puberty. Serum dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstendione, testosterone, dihydrotestosterone, LH and FSH were determined by radioimmunoassay. Patients of the first group had the clinical characteristics of testicular feminization secondary to absence of the androgen receptor. One of the five patients of the second group had deficient testosterone secretion but no enzymatic defect could be demonstrated. One of the subjects castrated before puberty had a deficiency in 17,20-desmolase. Therefore, evidence of a failure of the fetal testes could be found in only two of the twelve patients studied."} {"id": "PMID:160300", "title": "Distribution and variation of thromboplastic and fibrinolytic activity of dacron aortic grafts.", "content": "The distribution and variation of thromboplastic and fibrinolytic activity were studied in various layers of polyester grafts in the dog aorta. One, four and 36 months after implantation, these grafts were removed together with segments of normal arteries and veins and dissected into three layers. The thromboplastic and plasminogen activator activities in these layers were then determined. It was found that in the early post-operative period, the thromboplastic activity in the Dacron graft neointima is very high, whereas that of the plasminogen activator is relatively low. With the passage of time the thromboplastic activity decreases and plasminogen activator activity increases. Similarly the thromboplastic activity in the neomedial and neoadventitial layers of the graft falls as time elapses after the implantation and the fibrinolytic activity gradually increases. These changes in thromboplastic and fibrinolytic activity increase the danger of graft thrombosis in the early post-operative period whereas in the later period they are favourable to maintenance of graft patency.", "contents": "Distribution and variation of thromboplastic and fibrinolytic activity of dacron aortic grafts. The distribution and variation of thromboplastic and fibrinolytic activity were studied in various layers of polyester grafts in the dog aorta. One, four and 36 months after implantation, these grafts were removed together with segments of normal arteries and veins and dissected into three layers. The thromboplastic and plasminogen activator activities in these layers were then determined. It was found that in the early post-operative period, the thromboplastic activity in the Dacron graft neointima is very high, whereas that of the plasminogen activator is relatively low. With the passage of time the thromboplastic activity decreases and plasminogen activator activity increases. Similarly the thromboplastic activity in the neomedial and neoadventitial layers of the graft falls as time elapses after the implantation and the fibrinolytic activity gradually increases. These changes in thromboplastic and fibrinolytic activity increase the danger of graft thrombosis in the early post-operative period whereas in the later period they are favourable to maintenance of graft patency."} {"id": "PMID:160303", "title": "Facial dermatitis following friction treatment of acne.", "content": "A case report is presented herein of a twenty year old woman in whom an acute dermatitis of the face developed, which may have been caused by the use of a skin machine, possibly in combination with the use of a topical medication.", "contents": "Facial dermatitis following friction treatment of acne. A case report is presented herein of a twenty year old woman in whom an acute dermatitis of the face developed, which may have been caused by the use of a skin machine, possibly in combination with the use of a topical medication."} {"id": "PMID:160304", "title": "The sensitivity of Staphylococcus aureus 79 and 80, and Escherichia coli 95 to sodium salicylate, nicotinaldehyde singly, and in combination with nicotinic acid or nicotinamide.", "content": "Minimum bactericidal concentrations of salicylate, nicotinaldehyde singly, and in combination with nicotinic acid, or nicotinamide were determined for Staphylococcus aureus 79 and 80, and Escherichia coli 95, at inocula of 10(7)--10(2). The bactericidal dose of salicylate was affected markedly by the inoculum size. The bactericidal dose of nicotinic acid, or nicotinamide was affected only slightly by the size of the inoculum. Escherichia coli 95 was least affected by the inoculum size. Nicotinaldehyde is a far more bactericidal agent than is nicotinic acid, or nicotinamide; its bactericidal dose was approximately a tenth that of nicotinic acid, or nicotinamide. S. aureus 79 and 80 were affected synergistically by the combinations of nicotinic acid, or nicotinamide with salicylate. Nicotinaldehyde reduced the effectiveness of nicotinic acid, at all inoculum sizes, of S. aureus 79, while the reduction of effectiveness of nicotinamide was only found with inocula of 10(7)--10(5). At low inocula, 10(4)--10(2), an additive effect was demonstrated. S. aureus 80 was antagonistically affected, at all inoculum sizes, by the combination of nicotinaldehyde with nicotinamide, while with nicotinic acid a slight synergy was noted. In contrast, Escherichia coli 95 was antagonistically affected, at all inoculum sizes, by combinations of nicotinic acid, nicotinamide with salicylate, or nicotinaldehyde.", "contents": "The sensitivity of Staphylococcus aureus 79 and 80, and Escherichia coli 95 to sodium salicylate, nicotinaldehyde singly, and in combination with nicotinic acid or nicotinamide. Minimum bactericidal concentrations of salicylate, nicotinaldehyde singly, and in combination with nicotinic acid, or nicotinamide were determined for Staphylococcus aureus 79 and 80, and Escherichia coli 95, at inocula of 10(7)--10(2). The bactericidal dose of salicylate was affected markedly by the inoculum size. The bactericidal dose of nicotinic acid, or nicotinamide was affected only slightly by the size of the inoculum. Escherichia coli 95 was least affected by the inoculum size. Nicotinaldehyde is a far more bactericidal agent than is nicotinic acid, or nicotinamide; its bactericidal dose was approximately a tenth that of nicotinic acid, or nicotinamide. S. aureus 79 and 80 were affected synergistically by the combinations of nicotinic acid, or nicotinamide with salicylate. Nicotinaldehyde reduced the effectiveness of nicotinic acid, at all inoculum sizes, of S. aureus 79, while the reduction of effectiveness of nicotinamide was only found with inocula of 10(7)--10(5). At low inocula, 10(4)--10(2), an additive effect was demonstrated. S. aureus 80 was antagonistically affected, at all inoculum sizes, by the combination of nicotinaldehyde with nicotinamide, while with nicotinic acid a slight synergy was noted. In contrast, Escherichia coli 95 was antagonistically affected, at all inoculum sizes, by combinations of nicotinic acid, nicotinamide with salicylate, or nicotinaldehyde."} {"id": "PMID:160307", "title": "Factors contributing to impairment of the mixed lymphocyte reaction in leprosy.", "content": "Whereas the mixed lymphocyte reaction was essentially normal in inactive lepromatous leprosy and tuberculoid leprosy, it was severely impaired in active lepromatous leprosy. The impairment was found to be contributed by certain unknown factors in their plasma and subnormal reactivity of their T lymphocytes. The plasma derived from active lepromatous leprosy patients depressed the reaction of normal cells and normal plasma enhanced the reaction of active lepromatous lymphocytes. The cellular factor was studied by using a one-way reaction in which one of the two lymphocyte preparations was inactivated with mitomycin C. The impairment of blastogenesis of active lepromatous lymphocytes was partially reversed by substituting inactivated normal cells for similarly treated leprous cells, and conversely the response of normal allogeneic lymphocytes was depressed by substituting inactivated leprous lymphocytes as the stimulator cells.", "contents": "Factors contributing to impairment of the mixed lymphocyte reaction in leprosy. Whereas the mixed lymphocyte reaction was essentially normal in inactive lepromatous leprosy and tuberculoid leprosy, it was severely impaired in active lepromatous leprosy. The impairment was found to be contributed by certain unknown factors in their plasma and subnormal reactivity of their T lymphocytes. The plasma derived from active lepromatous leprosy patients depressed the reaction of normal cells and normal plasma enhanced the reaction of active lepromatous lymphocytes. The cellular factor was studied by using a one-way reaction in which one of the two lymphocyte preparations was inactivated with mitomycin C. The impairment of blastogenesis of active lepromatous lymphocytes was partially reversed by substituting inactivated normal cells for similarly treated leprous cells, and conversely the response of normal allogeneic lymphocytes was depressed by substituting inactivated leprous lymphocytes as the stimulator cells."} {"id": "PMID:160308", "title": "Initiation of DNA replication in chromosomes of Chinese hamster ovary cells.", "content": "The initiation of DNA replication and the subsequent chain elongation were studied using Chinese hamster ovary cells synchronized at the beginning of S phase. The cells were synchronized by a combination of mitotic selection and treatment with 5-fluorodeoxyuridine (FdU). The use of this drug at a concentration of 10(-5) M was found to effectively prevent the leakage of cells into S phase. Reversal of the FdU block by supplying thymidine resulted in the synchronous onset of initiation at multiple sites in each cell. The length of the nascent chains, as determined by autoradiography and velocity sedimentation in alkaline gradients, increased linearly with time during the first twenty minutes of S phase after release. We applied these procedures to study the effects of the length of an FdU block on the number of functional origins per cell, the rate of chain growth, and the rate of DNA synthesis per cell following reversal of the block. Although no change was noted in the rate of DNA synthesis in cells held at the beginning of S phase from 10.5 to 24 h after division, the rate of chain growth decreased from 0.94 to 0.28 microns per min. This decrease indicated that the number of functional origins increased markedly with length of FdU block. The calculated number of utilized origins per cell increased from 1,900 to 5,700. We also presented arguments that 1,900 origins per cell represents the approximate number of origins utilized by any cell held at the beginning of S phase for less than 10.5 h after division.", "contents": "Initiation of DNA replication in chromosomes of Chinese hamster ovary cells. The initiation of DNA replication and the subsequent chain elongation were studied using Chinese hamster ovary cells synchronized at the beginning of S phase. The cells were synchronized by a combination of mitotic selection and treatment with 5-fluorodeoxyuridine (FdU). The use of this drug at a concentration of 10(-5) M was found to effectively prevent the leakage of cells into S phase. Reversal of the FdU block by supplying thymidine resulted in the synchronous onset of initiation at multiple sites in each cell. The length of the nascent chains, as determined by autoradiography and velocity sedimentation in alkaline gradients, increased linearly with time during the first twenty minutes of S phase after release. We applied these procedures to study the effects of the length of an FdU block on the number of functional origins per cell, the rate of chain growth, and the rate of DNA synthesis per cell following reversal of the block. Although no change was noted in the rate of DNA synthesis in cells held at the beginning of S phase from 10.5 to 24 h after division, the rate of chain growth decreased from 0.94 to 0.28 microns per min. This decrease indicated that the number of functional origins increased markedly with length of FdU block. The calculated number of utilized origins per cell increased from 1,900 to 5,700. We also presented arguments that 1,900 origins per cell represents the approximate number of origins utilized by any cell held at the beginning of S phase for less than 10.5 h after division."} {"id": "PMID:160312", "title": "[Effect of pharmacological agents and coagulation of the n. raphe dorsalis on morphine effects].", "content": "The authors carried out studies on 96 female rats of Wistar strain and examined the influence of various pharmacological means and the coagulation of n. raphe dorsalis on cataleptic state, hyperthermia, and analgethic effect, induced by single administration of morphine. She found that LSD and preliminary treatment with parachlorphenylalanine caused enhancement of hyperthermic reaction to morphine. Acetyl-salicyliaccid had no effect on the hyperthermic reaction: dimenthydrinate and propranolol did alter it significantly, but cyproheptadine inhibited it. In respect to the cataleptic state, induced by morphine, she found that pharmacological means with various mechanism of action (parachlorphenylalatine, dimenhydrinate, cyproheptadine, propranolol and LSD) inhibited this states, but haloperidol enhanced it. She suggests that the hyperthermic reaction of morphine is due to, its action on serotoninergic neurones, regulating thermoregulation. She makes a guess that cataleptic state, induced by morphine, depends on the change in mediator interrelations (acethycholine, serotonine, dopamine). The lack of changes on the analhethic affect of morphine after coagulation of n. Raphe dorsalis, from which a part of accending serotoninergic pathways, supports the existing data in literature that both descending and accending serotoninergic pathways are of significance for analgethic action of morphine.", "contents": "[Effect of pharmacological agents and coagulation of the n. raphe dorsalis on morphine effects]. The authors carried out studies on 96 female rats of Wistar strain and examined the influence of various pharmacological means and the coagulation of n. raphe dorsalis on cataleptic state, hyperthermia, and analgethic effect, induced by single administration of morphine. She found that LSD and preliminary treatment with parachlorphenylalanine caused enhancement of hyperthermic reaction to morphine. Acetyl-salicyliaccid had no effect on the hyperthermic reaction: dimenthydrinate and propranolol did alter it significantly, but cyproheptadine inhibited it. In respect to the cataleptic state, induced by morphine, she found that pharmacological means with various mechanism of action (parachlorphenylalatine, dimenhydrinate, cyproheptadine, propranolol and LSD) inhibited this states, but haloperidol enhanced it. She suggests that the hyperthermic reaction of morphine is due to, its action on serotoninergic neurones, regulating thermoregulation. She makes a guess that cataleptic state, induced by morphine, depends on the change in mediator interrelations (acethycholine, serotonine, dopamine). The lack of changes on the analhethic affect of morphine after coagulation of n. Raphe dorsalis, from which a part of accending serotoninergic pathways, supports the existing data in literature that both descending and accending serotoninergic pathways are of significance for analgethic action of morphine."} {"id": "PMID:160313", "title": "Inhibitory role of brain stem serotoninergic neuron system on thyroid function in rat.", "content": "Thyroid function was investigated in adult male rats following the use experimental procedures which inhibit the activity of serotoninergic neuron system. Pharmacological blockade of the biosynthesis of sertonin by repeated administration of para-chlorophenylalanine (pCPA), or interruption (by Hal\u00e1sz knife) of the serotoninergic pathways of the brain stem which terminate on hypothalamic nuclei equally resulted in an augmentation of the following parameters of hypothalamo-hypophysial-thyroid activity: T/S ratio, pituitary and blood TSH levels and blood thyroxine concentration as well as TRH content of the hypothalamus. The results suggest that the central nervous serotoninergic neuron system plays an inhibitory role in the regulation of TSH secretion, presumably acting upon the hypothalamus, thereby inhibiting hypothalamic TRH secretion.", "contents": "Inhibitory role of brain stem serotoninergic neuron system on thyroid function in rat. Thyroid function was investigated in adult male rats following the use experimental procedures which inhibit the activity of serotoninergic neuron system. Pharmacological blockade of the biosynthesis of sertonin by repeated administration of para-chlorophenylalanine (pCPA), or interruption (by Hal\u00e1sz knife) of the serotoninergic pathways of the brain stem which terminate on hypothalamic nuclei equally resulted in an augmentation of the following parameters of hypothalamo-hypophysial-thyroid activity: T/S ratio, pituitary and blood TSH levels and blood thyroxine concentration as well as TRH content of the hypothalamus. The results suggest that the central nervous serotoninergic neuron system plays an inhibitory role in the regulation of TSH secretion, presumably acting upon the hypothalamus, thereby inhibiting hypothalamic TRH secretion."} {"id": "PMID:160314", "title": "Activation of Mg-ATPase (spectrin-dependent ATPase) by Ca2+.", "content": "The dependence of saponin-stimulated Mg-ATPase activity in the erythrocyte membrane on Ca2+ concentration was studied. In the membrane of freshly sampled human erythrocytes we found for this enzyme and Ca2+ an apparent dissociation constant of 0.611 mumol/l (SE +/- 0.106 mumol/l) and Hill coefficient of 0.93 (SE +/- 0.05). The enzyme is in most probability identical with Ca,Mg-ATPase of high affinity to Ca2+ described also as spectrin-dependent Ca,Mg-ATPase.", "contents": "Activation of Mg-ATPase (spectrin-dependent ATPase) by Ca2+. The dependence of saponin-stimulated Mg-ATPase activity in the erythrocyte membrane on Ca2+ concentration was studied. In the membrane of freshly sampled human erythrocytes we found for this enzyme and Ca2+ an apparent dissociation constant of 0.611 mumol/l (SE +/- 0.106 mumol/l) and Hill coefficient of 0.93 (SE +/- 0.05). The enzyme is in most probability identical with Ca,Mg-ATPase of high affinity to Ca2+ described also as spectrin-dependent Ca,Mg-ATPase."} {"id": "PMID:160316", "title": "Comparison between ATP-supported and GTP-supported phosphate turnover of the calcium-transporting sarcoplasmic reticulum membranes.", "content": "The study deals with the interrelationship of the phosphate-transferring activities of the calcium-transporting sarcoplasmic reticulum membrane vesicles: the phosphate exchange between nucleoside triphosphate (NTP) and nucleoside diphosphate (NDP) (NTP-NDP exchange), the calcium-dependent NTase, and the phosphorylation of NDP by inorganic phosphate in the presence of NTP (NTP-Pi exchange). Different nucleotides were used as phosphate donors and acceptors. It is demonstrated for the phosphate transfer from ITP to GDP that the NTP-NDP exchange exhibits ping-pong kinetics with Mg-ITP and unliganded GDP as substrates. The apparent affinities of the enzyme for the nucleoside diphosphate and triphosphate species are deduced according to this mechanism. The enzyme's affinity for the nucleoside triphosphates and diphosphates depends on its functional state being considerably lower under conditions of NTP-NDP exchange than during NTP splitting or NTP synthesis. ATP and GTP are split with the same low rates when calcium-activated NTPase is inhibited by high internal calcium concentrations after calcium transport has reached steady state. The rates of the NTP-NDP exchange reactions, however, differ by a factor of about 10 being approximately equal to 3 mumol . mg-1 . min-1 for ATP-ADP and only approximately equal to 0.3 mumol . mg-1 . min-1 (22 degrees C) for GTP-GDP. When the sarcoplasmic reticulum vesicles are made calcium-permeable, the calcium transport ATPase is turned on and the rates of GTP and ATP splitting increase about tenfold. Yet, while the rate of ATP-ADP exchange is little reduced, the rate of GTP-GDP exchange drops by approximately 50%. The persisting exchange activity of calcium-permeable vesicles demonstrates that high internal calcium concentrations are not required for the transfer of the protein-bound phosphoryl group to NDP during NTP-NDP exchange.", "contents": "Comparison between ATP-supported and GTP-supported phosphate turnover of the calcium-transporting sarcoplasmic reticulum membranes. The study deals with the interrelationship of the phosphate-transferring activities of the calcium-transporting sarcoplasmic reticulum membrane vesicles: the phosphate exchange between nucleoside triphosphate (NTP) and nucleoside diphosphate (NDP) (NTP-NDP exchange), the calcium-dependent NTase, and the phosphorylation of NDP by inorganic phosphate in the presence of NTP (NTP-Pi exchange). Different nucleotides were used as phosphate donors and acceptors. It is demonstrated for the phosphate transfer from ITP to GDP that the NTP-NDP exchange exhibits ping-pong kinetics with Mg-ITP and unliganded GDP as substrates. The apparent affinities of the enzyme for the nucleoside diphosphate and triphosphate species are deduced according to this mechanism. The enzyme's affinity for the nucleoside triphosphates and diphosphates depends on its functional state being considerably lower under conditions of NTP-NDP exchange than during NTP splitting or NTP synthesis. ATP and GTP are split with the same low rates when calcium-activated NTPase is inhibited by high internal calcium concentrations after calcium transport has reached steady state. The rates of the NTP-NDP exchange reactions, however, differ by a factor of about 10 being approximately equal to 3 mumol . mg-1 . min-1 for ATP-ADP and only approximately equal to 0.3 mumol . mg-1 . min-1 (22 degrees C) for GTP-GDP. When the sarcoplasmic reticulum vesicles are made calcium-permeable, the calcium transport ATPase is turned on and the rates of GTP and ATP splitting increase about tenfold. Yet, while the rate of ATP-ADP exchange is little reduced, the rate of GTP-GDP exchange drops by approximately 50%. The persisting exchange activity of calcium-permeable vesicles demonstrates that high internal calcium concentrations are not required for the transfer of the protein-bound phosphoryl group to NDP during NTP-NDP exchange."} {"id": "PMID:160317", "title": "Subcellular calcium localization and AT0-dependent Ca2+-uptake by smooth endoplasmic reticulum in an invertebrate photoreceptor cell. An ultrastrucutral, cytochemical and X-ray microanalytical study.", "content": "In Hirudo medicinalis an extensive and highly elaborate three dimensional network of smooth endoplasmic reticulum cisternae is found in very close structural relationship to the receptive (microvillar) membrane, as reported for many other invertebrates. A variant of the potassium pyroantimonate technique showed that these submicrovillar endoplasmic reticulum cisternae (SMC) and mitochondria are major intracellular calcium stores. Furthermore, using saponine-skinned photoreceptors for an in situ accumulation experiment, calcium oxalate precipitates in SMC demonstrate that this organelle is able to accumulate Ca2+ from a concentration of 2 x 10(-5) M, when ATP, Mg2+, and oxalate ions are present in the accumulation medium. This result provides direct evidence for the hypothesis that SMC may play a particularly important role in the regulation of intracellular ionized calcium in invertebrate photoreceptor cells. Morphological evidence supports this view.", "contents": "Subcellular calcium localization and AT0-dependent Ca2+-uptake by smooth endoplasmic reticulum in an invertebrate photoreceptor cell. An ultrastrucutral, cytochemical and X-ray microanalytical study. In Hirudo medicinalis an extensive and highly elaborate three dimensional network of smooth endoplasmic reticulum cisternae is found in very close structural relationship to the receptive (microvillar) membrane, as reported for many other invertebrates. A variant of the potassium pyroantimonate technique showed that these submicrovillar endoplasmic reticulum cisternae (SMC) and mitochondria are major intracellular calcium stores. Furthermore, using saponine-skinned photoreceptors for an in situ accumulation experiment, calcium oxalate precipitates in SMC demonstrate that this organelle is able to accumulate Ca2+ from a concentration of 2 x 10(-5) M, when ATP, Mg2+, and oxalate ions are present in the accumulation medium. This result provides direct evidence for the hypothesis that SMC may play a particularly important role in the regulation of intracellular ionized calcium in invertebrate photoreceptor cells. Morphological evidence supports this view."} {"id": "PMID:160322", "title": "Variations in serum androgens, estrogens, progestins, gonadotropins and prolactin levels in male rats from prepubertal to advanced age.", "content": "The concentrations of blood serum steroids from 12 to 450 days old male rats were determined by radioimmunoassay. Testosterone (T) was low (270 pg to less than 1 ng/ml) until day 42; adult levels (3--4 ng/ml) were attained by day 62 and declined tradually with advanced age. 5 alpha-dihydrotestosterone (5 alpha-DHT) did not change markedly (90--160 pg/ml) from prepubertal to advanced age. Except for a small peak on day 22, androstenedione (delta 4 A) levels ranged between 400-500 pg/ml in the adult but declined in older males. Progesterone (delta 4 P) rose steadily to a mean of 5.46 ng/ml at 52 days of age and dropped thereafter. High levels of estrone (268 +/- 38 pg/ml) and estradiol-17 beta (2.76 +/- 0.28 ng/ml) in 12 days old males are in contrast to the low estrogens (20-35 pg/ml) in adult animals. Both T/5 alpha-DHT and total T/estrogen ratios were low before puberty, increased in adults and decreased towards old age. The interplay between gonadotropin and prolactin, which exhibited reciprocal changes in the regulation of steroid production by the gonads with age, are discussed.", "contents": "Variations in serum androgens, estrogens, progestins, gonadotropins and prolactin levels in male rats from prepubertal to advanced age. The concentrations of blood serum steroids from 12 to 450 days old male rats were determined by radioimmunoassay. Testosterone (T) was low (270 pg to less than 1 ng/ml) until day 42; adult levels (3--4 ng/ml) were attained by day 62 and declined tradually with advanced age. 5 alpha-dihydrotestosterone (5 alpha-DHT) did not change markedly (90--160 pg/ml) from prepubertal to advanced age. Except for a small peak on day 22, androstenedione (delta 4 A) levels ranged between 400-500 pg/ml in the adult but declined in older males. Progesterone (delta 4 P) rose steadily to a mean of 5.46 ng/ml at 52 days of age and dropped thereafter. High levels of estrone (268 +/- 38 pg/ml) and estradiol-17 beta (2.76 +/- 0.28 ng/ml) in 12 days old males are in contrast to the low estrogens (20-35 pg/ml) in adult animals. Both T/5 alpha-DHT and total T/estrogen ratios were low before puberty, increased in adults and decreased towards old age. The interplay between gonadotropin and prolactin, which exhibited reciprocal changes in the regulation of steroid production by the gonads with age, are discussed."} {"id": "PMID:160324", "title": "Production of interferon in the murine mixed lymphocyte culture. II. Interferon production is a T cell-dependent function, independent of proliferation.", "content": "Interferon production occurs after two days of culture in murine mixed lymphocyte cultures (MLC). This was demonstrated in various combinations of mouse spleen cells differing at the major histocompatibility (H-2) locus. Interferon production could be demonstrated in one-way MLC when F1/parent combinations were used and in reactions in which one partner was treated by puromycin. After treatment of both cell populations with mitomycin C, interferon production occurred in the absence of lymphoproliferation. Interferon production in response to alloantigen did not occur in spleen cell cultures of nude mice and in cultures treated by anti-theta antiserum plus complement indicating that interferon production is a T cell-dependent function.", "contents": "Production of interferon in the murine mixed lymphocyte culture. II. Interferon production is a T cell-dependent function, independent of proliferation. Interferon production occurs after two days of culture in murine mixed lymphocyte cultures (MLC). This was demonstrated in various combinations of mouse spleen cells differing at the major histocompatibility (H-2) locus. Interferon production could be demonstrated in one-way MLC when F1/parent combinations were used and in reactions in which one partner was treated by puromycin. After treatment of both cell populations with mitomycin C, interferon production occurred in the absence of lymphoproliferation. Interferon production in response to alloantigen did not occur in spleen cell cultures of nude mice and in cultures treated by anti-theta antiserum plus complement indicating that interferon production is a T cell-dependent function."} {"id": "PMID:160325", "title": "Inhibition of E coli ATPase activity by a troponin component, TN-I, and by mitochondrial ATPase inhibitor.", "content": "The enzymic activity of Mg2+- or Ca2+-stimulated ATPase from Escherichia coli was inhibited by one of the troponin components, TN-I, and by mitochondrial ATPase inhibitor (F1-inhibitor). The inhibitory ability of component TN-I against Mg2+-stimulated AtPase activity was lost after digestion of component TN-I with trypsin. The Mg2+-stimulated ATPase activity inhibited by component TN-I was completely restored by the addition of another troponin component TN-C.", "contents": "Inhibition of E coli ATPase activity by a troponin component, TN-I, and by mitochondrial ATPase inhibitor. The enzymic activity of Mg2+- or Ca2+-stimulated ATPase from Escherichia coli was inhibited by one of the troponin components, TN-I, and by mitochondrial ATPase inhibitor (F1-inhibitor). The inhibitory ability of component TN-I against Mg2+-stimulated AtPase activity was lost after digestion of component TN-I with trypsin. The Mg2+-stimulated ATPase activity inhibited by component TN-I was completely restored by the addition of another troponin component TN-C."} {"id": "PMID:160326", "title": "The induction of diabetes in rats by intramuscular administration of streptozotocin.", "content": "Streptozotocin administered i.m. was as effective a diabetogenic agent as when administered i.v. This is useful, particularly for the induction of diabetes in small animals.", "contents": "The induction of diabetes in rats by intramuscular administration of streptozotocin. Streptozotocin administered i.m. was as effective a diabetogenic agent as when administered i.v. This is useful, particularly for the induction of diabetes in small animals."} {"id": "PMID:160348", "title": "A controlled clinical study comparing sulindac with ibuprofen and aspirin in the treatment of musculo-skeletal diseases.", "content": "Forty-six patients (seventeen male, twenty-nine female) with musculo-skeletal disease were put on a controlled clinical study comparing sulindac with ibuprofen and soluble aspirin. Twenty patients were treated with sulindac 200 mg twice daily, twelve received sulindac 100 mg twice daily, eight had ibuprofen 400 mg thrice daily and six treated with soluble aspirin 600 mg thrice daily. All patients did well on these drugs, but the ones on sulindac 200 mg twice daily showed better response than sulindac 100 mg twice daily. It proved to have the same efficiency as ibuprofen and soluble aspirin; but had less side-effects and also patients required to take the drug only twice daily to get relief because of its prolonged duration of action.", "contents": "A controlled clinical study comparing sulindac with ibuprofen and aspirin in the treatment of musculo-skeletal diseases. Forty-six patients (seventeen male, twenty-nine female) with musculo-skeletal disease were put on a controlled clinical study comparing sulindac with ibuprofen and soluble aspirin. Twenty patients were treated with sulindac 200 mg twice daily, twelve received sulindac 100 mg twice daily, eight had ibuprofen 400 mg thrice daily and six treated with soluble aspirin 600 mg thrice daily. All patients did well on these drugs, but the ones on sulindac 200 mg twice daily showed better response than sulindac 100 mg twice daily. It proved to have the same efficiency as ibuprofen and soluble aspirin; but had less side-effects and also patients required to take the drug only twice daily to get relief because of its prolonged duration of action."} {"id": "PMID:160349", "title": "Studies on untoward reactions to diphtheria and tetanus toxoids.", "content": "Adverse reactions to diphtheria and tetanus toxoids have frequently been reported. The cause of these reactions has been attributed to different factors, including sensitization by prior vaccination. However, this explanation does not hold for primary vaccination. In this case, undesirable reactions to diphtheria toxoid are most likely due to bacterial cellular fractions present in the vaccines. In fact, we were able to demonstrate that fortuitous contact with atoxigenic diphtheria strains can induce sensitization. Consequently, vaccination should be carried out with highly purified toxoids, so as to prevent untoward reactions due to the presence of impurities. It is also preferable to detoxify purified toxins, rather than to purify crude toxoids.", "contents": "Studies on untoward reactions to diphtheria and tetanus toxoids. Adverse reactions to diphtheria and tetanus toxoids have frequently been reported. The cause of these reactions has been attributed to different factors, including sensitization by prior vaccination. However, this explanation does not hold for primary vaccination. In this case, undesirable reactions to diphtheria toxoid are most likely due to bacterial cellular fractions present in the vaccines. In fact, we were able to demonstrate that fortuitous contact with atoxigenic diphtheria strains can induce sensitization. Consequently, vaccination should be carried out with highly purified toxoids, so as to prevent untoward reactions due to the presence of impurities. It is also preferable to detoxify purified toxins, rather than to purify crude toxoids."} {"id": "PMID:160351", "title": "Classical conditioning of profoundly retarded, multiply handicapped children.", "content": "A classical conditioning procedure was used with five profoundly retarded children with multiple handicaps in order to investigate basic learning processes in such children. Their chronological ages ranged from 48 to 108 months and their mental ages from 0 to 5.5 months. The procedure used a sound as the conditioned stimulus, a puff of air to the cornea as the unconditioned stimulus, and eye-blink as the conditioned response. Conditioning was established for the two most developmentally advanced children, and the intermediate pair showed different patterns of orienting response to the conditioned stimulus but no evidence of conditioning. The fifth and most developmentally delayed child did not respond to the stimuli. The extent to which these results can be generalised to the conditioning of profoundly retarded, multiply handicapped children is discussed.", "contents": "Classical conditioning of profoundly retarded, multiply handicapped children. A classical conditioning procedure was used with five profoundly retarded children with multiple handicaps in order to investigate basic learning processes in such children. Their chronological ages ranged from 48 to 108 months and their mental ages from 0 to 5.5 months. The procedure used a sound as the conditioned stimulus, a puff of air to the cornea as the unconditioned stimulus, and eye-blink as the conditioned response. Conditioning was established for the two most developmentally advanced children, and the intermediate pair showed different patterns of orienting response to the conditioned stimulus but no evidence of conditioning. The fifth and most developmentally delayed child did not respond to the stimuli. The extent to which these results can be generalised to the conditioning of profoundly retarded, multiply handicapped children is discussed."} {"id": "PMID:160352", "title": "[Congestive heart failure in genetic hypertrophic cardiomyopathies (ASH) (author's transl)].", "content": "Of a total sixtytwo patients covering all the spectrum of genetic ASH, who were studied by heart catheterization, M-mode echocardiography and phonomechano cardiography, five patients (four with the obstructive variety of the disease) showed clinical evidence of chronic congestive heart failure with ankle edema and hepatomegaly (group I). Their data were compared with those of fifteen \"obstructed\" patients who were not in heart decompensation (group II). No statistically significant differences were found between groups I and II in terms of L.V. internal transverse dimensions and in terms of L.V. systolic function. Conversely a statistically significant difference was found between the two groups in terms of left atrial and right ventricular dimensions (P less than 0,001), which were markedly increased in groups I. These findings strongly suggest that in patients with ASH and congestive heart failure there is a reduction in L.V. compliance (or distensibility), whereas L.V. systolic function is essentially preserved. The persistence of severe L.V. outflow obstruction in four patients of I group gives further confirmation to these observations. The use of beta-blockers (in association or not with cardiac glycosides) seems therefore to preserve its validity in the treatment of patients with ASH and heart failure, particulary when severe L.V. outflow obstruction is present. Cardiac glycosides are indicated in the forms with little or no obstruction to L.V. ejection.", "contents": "[Congestive heart failure in genetic hypertrophic cardiomyopathies (ASH) (author's transl)]. Of a total sixtytwo patients covering all the spectrum of genetic ASH, who were studied by heart catheterization, M-mode echocardiography and phonomechano cardiography, five patients (four with the obstructive variety of the disease) showed clinical evidence of chronic congestive heart failure with ankle edema and hepatomegaly (group I). Their data were compared with those of fifteen \"obstructed\" patients who were not in heart decompensation (group II). No statistically significant differences were found between groups I and II in terms of L.V. internal transverse dimensions and in terms of L.V. systolic function. Conversely a statistically significant difference was found between the two groups in terms of left atrial and right ventricular dimensions (P less than 0,001), which were markedly increased in groups I. These findings strongly suggest that in patients with ASH and congestive heart failure there is a reduction in L.V. compliance (or distensibility), whereas L.V. systolic function is essentially preserved. The persistence of severe L.V. outflow obstruction in four patients of I group gives further confirmation to these observations. The use of beta-blockers (in association or not with cardiac glycosides) seems therefore to preserve its validity in the treatment of patients with ASH and heart failure, particulary when severe L.V. outflow obstruction is present. Cardiac glycosides are indicated in the forms with little or no obstruction to L.V. ejection."} {"id": "PMID:160353", "title": "Antimetastatic and antitumor activity of a derivative of neocarzinostatin: an organic solvent- and water-soluble polymer-conjugated protein.", "content": "A highly lymphotropic derivative of a proteinaceous antitumor agent, Neocarzinostatin, was prepared by chemical conjugation of a water-soluble synthetic poly(maleic acid)-styrene oligomer. The derivative of 2.5 X 10(4) dalton exhibited a strong antitumor activity against AH109A and DBLA-6 as well as antimetastatic activity against metastatic AH109A with which experimental lymphatic metastasis was produced in rats. An increased lipophilicity and molecular weight of the derivative appear to be responsible for its improvement as lymphotropic antimetastatic agent.", "contents": "Antimetastatic and antitumor activity of a derivative of neocarzinostatin: an organic solvent- and water-soluble polymer-conjugated protein. A highly lymphotropic derivative of a proteinaceous antitumor agent, Neocarzinostatin, was prepared by chemical conjugation of a water-soluble synthetic poly(maleic acid)-styrene oligomer. The derivative of 2.5 X 10(4) dalton exhibited a strong antitumor activity against AH109A and DBLA-6 as well as antimetastatic activity against metastatic AH109A with which experimental lymphatic metastasis was produced in rats. An increased lipophilicity and molecular weight of the derivative appear to be responsible for its improvement as lymphotropic antimetastatic agent."} {"id": "PMID:160355", "title": "[Effect of the dose of ptsI- and ptsH-genes on carbohydrate transport and regulation of lac-operon activity in Escherichia coli K-12].", "content": "Phage Mu-1 cts61 was used for transposition of pts1 and ptsH genes. The received F'-factors AUF2 and AUF3 carry short fragments of the bacterial chromosome. Merodiploid strains with double pts genes were selected in sexduction crosses with the appropriate recA recipients. Effect of the gene dose was not registered in pts+/pts+ strains in the case of accumulation of the substrates of the phosphoenolpyruvate-dependent phosphotransferase system (PTS) and in the case of bacterial growth in the presence of these carbohydrates. This indicates that the enzyme (enzymes) II of the PTS is the limiting step in the transpost process. Induction of beta-galactosidase and the growth on carbohydrates not transported via the PTS (maltose, lactose) were greatly reduced in pts mutant. Introduction of the pts+ allele with episome lead to the restoration of the two above processes. These data show that the phospho approximately HPr generating system of the PTS is directly (or in indirect manner) involved in the regulation of catabolite-sensitive operons. Glucose repression was markedly increased in pts+/pts+ merodiploids as compared with pts+/pts- ones and with pts+ bacteria. Possible mechanisms of this effect are discussed.", "contents": "[Effect of the dose of ptsI- and ptsH-genes on carbohydrate transport and regulation of lac-operon activity in Escherichia coli K-12]. Phage Mu-1 cts61 was used for transposition of pts1 and ptsH genes. The received F'-factors AUF2 and AUF3 carry short fragments of the bacterial chromosome. Merodiploid strains with double pts genes were selected in sexduction crosses with the appropriate recA recipients. Effect of the gene dose was not registered in pts+/pts+ strains in the case of accumulation of the substrates of the phosphoenolpyruvate-dependent phosphotransferase system (PTS) and in the case of bacterial growth in the presence of these carbohydrates. This indicates that the enzyme (enzymes) II of the PTS is the limiting step in the transpost process. Induction of beta-galactosidase and the growth on carbohydrates not transported via the PTS (maltose, lactose) were greatly reduced in pts mutant. Introduction of the pts+ allele with episome lead to the restoration of the two above processes. These data show that the phospho approximately HPr generating system of the PTS is directly (or in indirect manner) involved in the regulation of catabolite-sensitive operons. Glucose repression was markedly increased in pts+/pts+ merodiploids as compared with pts+/pts- ones and with pts+ bacteria. Possible mechanisms of this effect are discussed."} {"id": "PMID:160356", "title": "[Population analysis of minor hemoglobin fractions. I. Hemoglobin A2].", "content": "The inhabitants of 7 isolated villages (of different nationalities) and of 5 panmictic populations were studied. Populational and segregation analyses of Hb A2 in 3036 normal and 150 heterozygous individuals for beta- and delta beta-thalassemia were carried out. The Hb A2 levels in some populations are established to deviate from the normal distribution. Bimodal dependency of the levels of Hb A2 distribution is demonstrated, which suggests the existance of heterogenous subpopulations by the Hb A2 level. The segregation analysis has revealed distinct genetic determination of Hb A2 levels. There was a good correlation between Hb A2 and Hb F values (r=-0.82).", "contents": "[Population analysis of minor hemoglobin fractions. I. Hemoglobin A2]. The inhabitants of 7 isolated villages (of different nationalities) and of 5 panmictic populations were studied. Populational and segregation analyses of Hb A2 in 3036 normal and 150 heterozygous individuals for beta- and delta beta-thalassemia were carried out. The Hb A2 levels in some populations are established to deviate from the normal distribution. Bimodal dependency of the levels of Hb A2 distribution is demonstrated, which suggests the existance of heterogenous subpopulations by the Hb A2 level. The segregation analysis has revealed distinct genetic determination of Hb A2 levels. There was a good correlation between Hb A2 and Hb F values (r=-0.82)."} {"id": "PMID:160357", "title": "[Medico-genetic study of the population of Uzbekistan. VI. Hereditary pathology among the populations of 4 regions of the Kashkadarinskaia area].", "content": "The screening for families burdened with multiple cases of non-infectious diseases, the diagnostic of those diseases and the investigation of relations between the population structure and the distribution of hereditary diseases in 4 districts of the Kashkadarja province were carried out. On the basis of the data obtained the load of excessive hereditary diseases was calculated and nosological spectrum was described; it included more than 30 different diseases. The study of spatial distribution of recessive diseases has shown that the load of hereditary diseases may be accounted for the positive assortative matings. The high level of interpopulation migration prevents from the local accumulation of a certain hereditary disease.", "contents": "[Medico-genetic study of the population of Uzbekistan. VI. Hereditary pathology among the populations of 4 regions of the Kashkadarinskaia area]. The screening for families burdened with multiple cases of non-infectious diseases, the diagnostic of those diseases and the investigation of relations between the population structure and the distribution of hereditary diseases in 4 districts of the Kashkadarja province were carried out. On the basis of the data obtained the load of excessive hereditary diseases was calculated and nosological spectrum was described; it included more than 30 different diseases. The study of spatial distribution of recessive diseases has shown that the load of hereditary diseases may be accounted for the positive assortative matings. The high level of interpopulation migration prevents from the local accumulation of a certain hereditary disease."} {"id": "PMID:160358", "title": "[Frequency of chromosome variants in human populations].", "content": "Chromosome variants were analyzed in the course of the population chromosome investigation of 6000 newborns and clinical cytogenetic studies of 403 married couples with recurrent spontaneous abortions, stillbirths or offsprings having congenital malformations or Down's syndrome. The following variants were determined: 1) Igh+, 9gh+, 16gh+ - the enlargement of the secondary constrictions of the size, more than 1/4 of the long arm of the chromosome; 2) Dp+ or Gp+ - the enlargement of the short arms of acrocentrics, their size being more than the short arm of the chromosome 18; 3) Ds+ or Gs - large satellites of the acrocentrics which are equal or more than the thickness of the chromatids of the long arms; 4) Es+ - satellites on the short arms of the chromosomes 17 or 18; 5) Dss of Gss - double satellites; 6) Yq+ - the enlargement of the long arm of Y chromosome, the size of which being more than G chromosome; 7) Yq- - deletion of the long arm of Y chromosome, the size of the long arm being less than chromosomes 21--22. The total frequency of variants in newborns was 12.8/1000 births. The incidence of different types of variants per 1000 births was as follows: Igh+ - 0.33; 9gh+ - 0.17; 16gh+ - 0.50; Ds+ - 2.33; Dp+ - 1.50; Dp- - 0.17; Gs+ - 0.83; Gp+ - 2.17; Yq+ - 6.91/1000 males; Yg- - 0.99/1000 males; double variants - 0.33; other variants - 0.33. 4.0% of married couples with recurrent spontaneous abortions had major chromosome aberrations, 14.6% - extreme variants of chromosomes. Among 113 couples with the history of congenital malformations in their offsprings major chromosome abnormalities were found in 4.4%, chromosome variants - 13.3%. The frequency of chromosome variants among 139 patients with Down's syndrome was 7.2%. In one case Robertsonian translocation t(DqGa) was determined. The most frequent types of variant chromosomes were Ds+, Dp+, Es+, Yq+.", "contents": "[Frequency of chromosome variants in human populations]. Chromosome variants were analyzed in the course of the population chromosome investigation of 6000 newborns and clinical cytogenetic studies of 403 married couples with recurrent spontaneous abortions, stillbirths or offsprings having congenital malformations or Down's syndrome. The following variants were determined: 1) Igh+, 9gh+, 16gh+ - the enlargement of the secondary constrictions of the size, more than 1/4 of the long arm of the chromosome; 2) Dp+ or Gp+ - the enlargement of the short arms of acrocentrics, their size being more than the short arm of the chromosome 18; 3) Ds+ or Gs - large satellites of the acrocentrics which are equal or more than the thickness of the chromatids of the long arms; 4) Es+ - satellites on the short arms of the chromosomes 17 or 18; 5) Dss of Gss - double satellites; 6) Yq+ - the enlargement of the long arm of Y chromosome, the size of which being more than G chromosome; 7) Yq- - deletion of the long arm of Y chromosome, the size of the long arm being less than chromosomes 21--22. The total frequency of variants in newborns was 12.8/1000 births. The incidence of different types of variants per 1000 births was as follows: Igh+ - 0.33; 9gh+ - 0.17; 16gh+ - 0.50; Ds+ - 2.33; Dp+ - 1.50; Dp- - 0.17; Gs+ - 0.83; Gp+ - 2.17; Yq+ - 6.91/1000 males; Yg- - 0.99/1000 males; double variants - 0.33; other variants - 0.33. 4.0% of married couples with recurrent spontaneous abortions had major chromosome aberrations, 14.6% - extreme variants of chromosomes. Among 113 couples with the history of congenital malformations in their offsprings major chromosome abnormalities were found in 4.4%, chromosome variants - 13.3%. The frequency of chromosome variants among 139 patients with Down's syndrome was 7.2%. In one case Robertsonian translocation t(DqGa) was determined. The most frequent types of variant chromosomes were Ds+, Dp+, Es+, Yq+."} {"id": "PMID:160359", "title": "A rightward promoter to the left of the att site of lambda phage DNA: possible participant in site-specific recombination.", "content": "The binding has been studied of Escherichia coli RNA-polymerase to the fragments of lambda DNA obtained by digestion with restriction endonucleases BsuI, HindIII, BamHI, EcoRI and HindII + III. There are at least six sites of RNA-polymerase binding in the b2-region. In vitro transcription of those BsuI-fragments of the b2-region which contain six binding sites is rightward. Therefore, the fragments contain promoters rather than mere RNA-polymerase binding sites. One of the promoters of the b2 region named patt was calculated to be about 50 bp to the left of the att site. We postulate that this promoter might correspond to the hef-target which was described as important for the site-specific recombination.", "contents": "A rightward promoter to the left of the att site of lambda phage DNA: possible participant in site-specific recombination. The binding has been studied of Escherichia coli RNA-polymerase to the fragments of lambda DNA obtained by digestion with restriction endonucleases BsuI, HindIII, BamHI, EcoRI and HindII + III. There are at least six sites of RNA-polymerase binding in the b2-region. In vitro transcription of those BsuI-fragments of the b2-region which contain six binding sites is rightward. Therefore, the fragments contain promoters rather than mere RNA-polymerase binding sites. One of the promoters of the b2 region named patt was calculated to be about 50 bp to the left of the att site. We postulate that this promoter might correspond to the hef-target which was described as important for the site-specific recombination."} {"id": "PMID:160360", "title": "A comprehensive molecular map of bacteriophage lambda.", "content": "Physical and genetic mapping of deletion mutations has been correlated with the available molecular sizes of the lambda gene products and the DNA base sequence to construct a comprehensive molecular map of the phage lambda genome. The physical length of the DNA making up the left arm from the cos site through gene J is not sufficient to account in a nonoverlapping manner for all the proteins of the sizes reported to be coded, especially in the Nu1--C region. In the right arm all the coding capacity has not been accounted for, and it appears to be oversaturated only in the gam-ral region. The positions of several IS and Tn elements, and of restriction endonuclease cleavage sites are specified.", "contents": "A comprehensive molecular map of bacteriophage lambda. Physical and genetic mapping of deletion mutations has been correlated with the available molecular sizes of the lambda gene products and the DNA base sequence to construct a comprehensive molecular map of the phage lambda genome. The physical length of the DNA making up the left arm from the cos site through gene J is not sufficient to account in a nonoverlapping manner for all the proteins of the sizes reported to be coded, especially in the Nu1--C region. In the right arm all the coding capacity has not been accounted for, and it appears to be oversaturated only in the gam-ral region. The positions of several IS and Tn elements, and of restriction endonuclease cleavage sites are specified."} {"id": "PMID:160361", "title": "The organization of a nuclear DNA sequence from a higher plant: molecular cloning and characterization of soybean ribosomal DNA.", "content": "The recombinant DNA vector, lambda Charon 4A, was used to construct a library of DNA sequences from the genomic DNA of soybean (Glycine max). To define the organization of ribosomal DNA (rDNA) in the soybean genome, clones containing sequences complementary to both 17S and 25S rRNA have been isolated from this library and used in conjunction with Southern blot hybridization. The rRNA genes are tandemly reiterated with a relatively small unit repeat length of 7.8 kb. There is no heterogeneity in the length of the rDNA repeat units although they display limited differences in either base sequence or pattern of methylation. The cloned rDNA sequences are shown to comprise the entire repeat unit and have been used to obtain a detailed restriction map as well as an approximate transcription map of soybean rRNA genes. The cloning of rDNA from soybean suggests that recombinant DNA techniques can be successfully applied to the genomic DNA of higher plants despite the high degree of methylation exhibited by plant DNA.", "contents": "The organization of a nuclear DNA sequence from a higher plant: molecular cloning and characterization of soybean ribosomal DNA. The recombinant DNA vector, lambda Charon 4A, was used to construct a library of DNA sequences from the genomic DNA of soybean (Glycine max). To define the organization of ribosomal DNA (rDNA) in the soybean genome, clones containing sequences complementary to both 17S and 25S rRNA have been isolated from this library and used in conjunction with Southern blot hybridization. The rRNA genes are tandemly reiterated with a relatively small unit repeat length of 7.8 kb. There is no heterogeneity in the length of the rDNA repeat units although they display limited differences in either base sequence or pattern of methylation. The cloned rDNA sequences are shown to comprise the entire repeat unit and have been used to obtain a detailed restriction map as well as an approximate transcription map of soybean rRNA genes. The cloning of rDNA from soybean suggests that recombinant DNA techniques can be successfully applied to the genomic DNA of higher plants despite the high degree of methylation exhibited by plant DNA."} {"id": "PMID:160369", "title": "[The nutritional effects of the \"classical\" steal syndrome. (Steal syndrome--effect or phenomenon?) (author's transl)].", "content": "Since the steal syndrome was first described, many symptoms have, rightly or wrongly, been ascribed to this. The classical steal syndrome, as described by Revich et al for the subclavian artery, produces special nutritional effects, but these are also found in other vascular territories, particularly when the unpaired branches of the abdominal aorta are involved. The abnormal haemodynamics in a circumscribed arterial territory can be demonstrated radiologically before the full syndrome has developed. It would therefore be more precise to speak of a steal phenomenon or steal effect depending on whether there are objective or subjective changes.", "contents": "[The nutritional effects of the \"classical\" steal syndrome. (Steal syndrome--effect or phenomenon?) (author's transl)]. Since the steal syndrome was first described, many symptoms have, rightly or wrongly, been ascribed to this. The classical steal syndrome, as described by Revich et al for the subclavian artery, produces special nutritional effects, but these are also found in other vascular territories, particularly when the unpaired branches of the abdominal aorta are involved. The abnormal haemodynamics in a circumscribed arterial territory can be demonstrated radiologically before the full syndrome has developed. It would therefore be more precise to speak of a steal phenomenon or steal effect depending on whether there are objective or subjective changes."} {"id": "PMID:160370", "title": "[Active and passive vascular involvement in tumours and tumour-like processes in the extremities (author's transl)].", "content": "Angiography for tumours of the extremities may demonstrate active or passive involvement of vessels by the tumour. This technique has been used for a considerable time for the diagnosis and differentiation of bone tumours. Angiography is particularly suitable for distinguishing between benign and malignant tumours of soft tissues. Non-neoplastic space-occupying lesions which can be elucidated by angiography include aneurysms, haematomas, inflammatory processes and abscesses.", "contents": "[Active and passive vascular involvement in tumours and tumour-like processes in the extremities (author's transl)]. Angiography for tumours of the extremities may demonstrate active or passive involvement of vessels by the tumour. This technique has been used for a considerable time for the diagnosis and differentiation of bone tumours. Angiography is particularly suitable for distinguishing between benign and malignant tumours of soft tissues. Non-neoplastic space-occupying lesions which can be elucidated by angiography include aneurysms, haematomas, inflammatory processes and abscesses."} {"id": "PMID:160371", "title": "[Classification and course of cerebral infarcts on computer tomography (author's transl)].", "content": "The typical computer tomographic signs of ischaemic cerebral infarct are discussed on the basis of 631 cases. Infarcts have three typical stages. Stage I, one week, fresh infarct with signs of oedema (space-occupying lesion with an unsharp margin, slightly reduced density, lack of contrast uptake). Stage II, second to fourth week, reduction in the oedema. Frequently very marked contrast enhancement of the cortex and basal nuclei. Stage III, later than four weeks. Development of malacic cysts, with further reduction in density and size. Development of homolateral atrophy. The computer tomographic diagnosis of cerebral infarcts during Stage I is often very difficult. Distinction from infiltrating tumour is often possible only after further observation. The diagnosis of cerebral infarcts in stages II and III is possible in most cases. Haemorrhagic cerebral infarcts do not follow a temporal pattern as accurately as anaemic infarcts. They show circular increase in contrast of slowly diminishing size. The increased contrast persists considerably longer and is clearly distinguished from that in an anaemic cerebral infarct.", "contents": "[Classification and course of cerebral infarcts on computer tomography (author's transl)]. The typical computer tomographic signs of ischaemic cerebral infarct are discussed on the basis of 631 cases. Infarcts have three typical stages. Stage I, one week, fresh infarct with signs of oedema (space-occupying lesion with an unsharp margin, slightly reduced density, lack of contrast uptake). Stage II, second to fourth week, reduction in the oedema. Frequently very marked contrast enhancement of the cortex and basal nuclei. Stage III, later than four weeks. Development of malacic cysts, with further reduction in density and size. Development of homolateral atrophy. The computer tomographic diagnosis of cerebral infarcts during Stage I is often very difficult. Distinction from infiltrating tumour is often possible only after further observation. The diagnosis of cerebral infarcts in stages II and III is possible in most cases. Haemorrhagic cerebral infarcts do not follow a temporal pattern as accurately as anaemic infarcts. They show circular increase in contrast of slowly diminishing size. The increased contrast persists considerably longer and is clearly distinguished from that in an anaemic cerebral infarct."} {"id": "PMID:160372", "title": "[CT of the pelvis and abdomen during childhood (author's transl)].", "content": "The use of CT in the abdomen and pelvis in 25 children is described. Certain problems which reduce the value of the technique are discussed; these include the lack of intra- and retro-peritoneal fat, movement artefacts, the importance of exact indications and the problems of radiation dosage.", "contents": "[CT of the pelvis and abdomen during childhood (author's transl)]. The use of CT in the abdomen and pelvis in 25 children is described. Certain problems which reduce the value of the technique are discussed; these include the lack of intra- and retro-peritoneal fat, movement artefacts, the importance of exact indications and the problems of radiation dosage."} {"id": "PMID:160373", "title": "[A comparison of computer tomography and ultrasound for the demonstration of vessels in the abdomen and retroperitoneal space (author's transl)].", "content": "The value of computer tomography and ultrasound for demonstrating vessels in the abdomen and retroperitoneal space was compared. The methods were equal in their ability to demonstrate the major vessels situated centrally, but computer tomography proved better at differentiating arteries and veins situated peripherally. On the other hand, sonography proved a simple means of differentiating intrahepatic vascular structures.", "contents": "[A comparison of computer tomography and ultrasound for the demonstration of vessels in the abdomen and retroperitoneal space (author's transl)]. The value of computer tomography and ultrasound for demonstrating vessels in the abdomen and retroperitoneal space was compared. The methods were equal in their ability to demonstrate the major vessels situated centrally, but computer tomography proved better at differentiating arteries and veins situated peripherally. On the other hand, sonography proved a simple means of differentiating intrahepatic vascular structures."} {"id": "PMID:160374", "title": "[Computer tomography following blunt abdominal trauma (author's transl)].", "content": "The computer tomographic appearances of lesions of parenchymatous organs following blunt abdominal trauma are described in 13 patients (five liver, four renal, two splenic and two pancreatic injuries). The value of abdominal computer tomography is discussed in relation to the interval between injury and time of abdominal examination and compared with the diagnostic value of abdominal angiography.", "contents": "[Computer tomography following blunt abdominal trauma (author's transl)]. The computer tomographic appearances of lesions of parenchymatous organs following blunt abdominal trauma are described in 13 patients (five liver, four renal, two splenic and two pancreatic injuries). The value of abdominal computer tomography is discussed in relation to the interval between injury and time of abdominal examination and compared with the diagnostic value of abdominal angiography."} {"id": "PMID:160375", "title": "[Computer tomographic demonstration of haematomas in the pelvis and abdomen (author's transl)].", "content": "Retro- and intra-peritoneal haematomas have been demonstrated in 19 patients by computer tomography. Absorption values varied from 0 to 65 Hounsfield units. Absorption values are high shortly after the trauma, but fall during the following days and weeks because of absorption and enzymatic chances of the haemaglobin and protein. A diagnosis can only be made with a knowledge of the clinical background. Tumours, abscesses and cysts must be considered in the differential diagnosis. Unlike conventional radiography, haematomas can be directly demonstrated by computer tomography. Angiography may demonstrate the point of bleeding when there is no haematoma, or if an haematoma fails to develop because bleeding is taking place into a hollow organ or a duct.", "contents": "[Computer tomographic demonstration of haematomas in the pelvis and abdomen (author's transl)]. Retro- and intra-peritoneal haematomas have been demonstrated in 19 patients by computer tomography. Absorption values varied from 0 to 65 Hounsfield units. Absorption values are high shortly after the trauma, but fall during the following days and weeks because of absorption and enzymatic chances of the haemaglobin and protein. A diagnosis can only be made with a knowledge of the clinical background. Tumours, abscesses and cysts must be considered in the differential diagnosis. Unlike conventional radiography, haematomas can be directly demonstrated by computer tomography. Angiography may demonstrate the point of bleeding when there is no haematoma, or if an haematoma fails to develop because bleeding is taking place into a hollow organ or a duct."} {"id": "PMID:160376", "title": "[Computer tomography in the diagnosis of local recurrences after resection for carcinoma of the rectum (author's transl)].", "content": "Presacral or pelvic floor tumour recurrence after abdomino-perineal resection for rectal or anal carcinomas has not been amenable to early radiological diagnosis. Computer tomography is a procedure which can demonstrate recurrences of two to three cm. Within the pelvis with certainty. The reliability of the method has been demonstrated in 27 patients suspected of having recurrences. The effect of demonstrating or excluding a recurrence on subsequent treatment is discussed. The value of computer tomographic examination of the pelvis for demonstrating the position and extent of a recurrence, the displacement of neighbouring organs, destruction of the pelvis and involvement of iliac lymph nodes is shown.", "contents": "[Computer tomography in the diagnosis of local recurrences after resection for carcinoma of the rectum (author's transl)]. Presacral or pelvic floor tumour recurrence after abdomino-perineal resection for rectal or anal carcinomas has not been amenable to early radiological diagnosis. Computer tomography is a procedure which can demonstrate recurrences of two to three cm. Within the pelvis with certainty. The reliability of the method has been demonstrated in 27 patients suspected of having recurrences. The effect of demonstrating or excluding a recurrence on subsequent treatment is discussed. The value of computer tomographic examination of the pelvis for demonstrating the position and extent of a recurrence, the displacement of neighbouring organs, destruction of the pelvis and involvement of iliac lymph nodes is shown."} {"id": "PMID:160377", "title": "[Computer tomography and retroperitoneal fibrosis (Ormond's disease) (author's transl)].", "content": "Four patients with retroperitoneal fibrosis (Ormond's disease) were examined by computer tomography; the appearances are described and the differential diagnosis discussed. Computer tomography clearly defines the proliferative-inflammatory process and together with conventional radiology, angiography and lymphangiography it permits a presumptive diagnosis of retroperitoneal fibrosis. The non-invasive nature of computer tomography makes it the method of choice for follow-up of this disease.", "contents": "[Computer tomography and retroperitoneal fibrosis (Ormond's disease) (author's transl)]. Four patients with retroperitoneal fibrosis (Ormond's disease) were examined by computer tomography; the appearances are described and the differential diagnosis discussed. Computer tomography clearly defines the proliferative-inflammatory process and together with conventional radiology, angiography and lymphangiography it permits a presumptive diagnosis of retroperitoneal fibrosis. The non-invasive nature of computer tomography makes it the method of choice for follow-up of this disease."} {"id": "PMID:160378", "title": "[Computer tomography for rare soft tissue tumours of the extremities (author's transl)].", "content": "Five patients with undiagnosed soft tissue masses in the extremities were examined and in two a pathological diagnosis could be made. One was an extensive, invasive fibroma (desmoid) 22 cm long which could be followed from the thigh almost into the pelvis. It was sharply demarkated form the surrounding muscles and of higher density. The second case was a 12 cm long cavernous haemangioma in the semi-membranosus muscle. This was originally hypo-dense, but showed marked increase in its density after the administration of contrast.", "contents": "[Computer tomography for rare soft tissue tumours of the extremities (author's transl)]. Five patients with undiagnosed soft tissue masses in the extremities were examined and in two a pathological diagnosis could be made. One was an extensive, invasive fibroma (desmoid) 22 cm long which could be followed from the thigh almost into the pelvis. It was sharply demarkated form the surrounding muscles and of higher density. The second case was a 12 cm long cavernous haemangioma in the semi-membranosus muscle. This was originally hypo-dense, but showed marked increase in its density after the administration of contrast."} {"id": "PMID:160379", "title": "[Therapeutic embolisation of visceral arteries. Animal experiments, early clinical experience, introduction of a new embolising material (author's transl)].", "content": "Silicone elastomer was found to be suitable embolsing material in animal experiments and has been used in 16 patients. It produces permanent vascular occlusion, is easy to use, well tolerated and can be steam sterilised. The disadvantage of the method is the time taken to prepare it in the laboratory. Embolisation of tumours was successful in all cases; angiography nine months later showed that the vessels had remained occluded and that the tumours had ceased to grow or become smaller. The development of collateral vessels shows that this is only a palliative procedure and that surgery remains the main form of treatment. In ten of the 16 patients, the course of the disease was influenced beneficially.", "contents": "[Therapeutic embolisation of visceral arteries. Animal experiments, early clinical experience, introduction of a new embolising material (author's transl)]. Silicone elastomer was found to be suitable embolsing material in animal experiments and has been used in 16 patients. It produces permanent vascular occlusion, is easy to use, well tolerated and can be steam sterilised. The disadvantage of the method is the time taken to prepare it in the laboratory. Embolisation of tumours was successful in all cases; angiography nine months later showed that the vessels had remained occluded and that the tumours had ceased to grow or become smaller. The development of collateral vessels shows that this is only a palliative procedure and that surgery remains the main form of treatment. In ten of the 16 patients, the course of the disease was influenced beneficially."} {"id": "PMID:160380", "title": "[Indications and value of treatment by catheter occlusion (author's transl)].", "content": "The value of the catheter occlusion therapy is analyzed in 92 cases retrospectively, and the indication, and complication risk of these procedures are considered. In the following vessel areas occlusion with different methods have been performed with decreasing frequency; kidneys, pelvis, legs, gastrointestinal tract, external carotid and internal carotid artery. Serious complications have been observed in therapeutic investigations at the head, especially in occlusions of the external carotid artery. In this group embolisation therapy should be performed with strict indication only.", "contents": "[Indications and value of treatment by catheter occlusion (author's transl)]. The value of the catheter occlusion therapy is analyzed in 92 cases retrospectively, and the indication, and complication risk of these procedures are considered. In the following vessel areas occlusion with different methods have been performed with decreasing frequency; kidneys, pelvis, legs, gastrointestinal tract, external carotid and internal carotid artery. Serious complications have been observed in therapeutic investigations at the head, especially in occlusions of the external carotid artery. In this group embolisation therapy should be performed with strict indication only."} {"id": "PMID:160381", "title": "[Percutaneous nephropyelostomy: indications and technique (author's transl)].", "content": "Percutaneous nephropyelostomy has been performed on 24 patients. The method is simple, has few complications and can be performed rapidly; it can be recommended for both temporary and permanent supravesical urinary drainage. It represents an improvement in urologic techniques.", "contents": "[Percutaneous nephropyelostomy: indications and technique (author's transl)]. Percutaneous nephropyelostomy has been performed on 24 patients. The method is simple, has few complications and can be performed rapidly; it can be recommended for both temporary and permanent supravesical urinary drainage. It represents an improvement in urologic techniques."} {"id": "PMID:160382", "title": "[Ultrasonography of the adrenals--limits of a real time scanner (author's transl)].", "content": "Sonography is an efficient, non invasive diagnostic tool in evaluating pathological enlargement of the adrenals. In 11 out of 27 patients, who had adrenal sonography, a tumor diagnosis was established. In 7 patients the sonographic findings and diagnosis were proved by scintigraphy, surgery and histology. With conventional ultrasound technique one cannot see the normal and nodular hyperplastic adrenal. At the same time we believe, tumors smaller than 2.5 cm cannot be diagnosed accurately in general. Some problems of adrenal sonography could be eliminated with most recent ultrasound technology. (Grayscale processing, scan converter system, electronically focused transducers with higher frequencies). In future patients with pathologies in the adrenals can be evaluated non-invasive and definitely by ultrasound and computerized tomography.", "contents": "[Ultrasonography of the adrenals--limits of a real time scanner (author's transl)]. Sonography is an efficient, non invasive diagnostic tool in evaluating pathological enlargement of the adrenals. In 11 out of 27 patients, who had adrenal sonography, a tumor diagnosis was established. In 7 patients the sonographic findings and diagnosis were proved by scintigraphy, surgery and histology. With conventional ultrasound technique one cannot see the normal and nodular hyperplastic adrenal. At the same time we believe, tumors smaller than 2.5 cm cannot be diagnosed accurately in general. Some problems of adrenal sonography could be eliminated with most recent ultrasound technology. (Grayscale processing, scan converter system, electronically focused transducers with higher frequencies). In future patients with pathologies in the adrenals can be evaluated non-invasive and definitely by ultrasound and computerized tomography."} {"id": "PMID:160383", "title": "[Studies on the reliability of the 99mTc-uptake as a measure of thyroidal stimulation (author's transl)].", "content": "In 44 patients with stimulated goitre the trapping kinetics of 131I-iodide and 99mTc-pertechnetate are analyzed having corrected for different size of the thyroid and different physical properties of the tracers under use. Unidirectional iodide clearance (UDCL) is chosen as reliable estimator of thyroidal stimulation. UDCL shows strong correlation to iodide uptake tests and the correlation to pertechnetate uptake tests is sufficiently strong for semiquantitative evaluation of thyroidal stimulation. Under the conditions of clinical routine work the reproducibility of pertechnetate uptake tests exceeds that of iodide, thus, pertechnetate uptakes are more suitable for evaluation of regulation tests, i.e. suppression test and stimulation test with TSH. 99mTc-thyroid-uptake (TcTU) 20 min after injection is a useful parameter of thyroidal stimulation for clinical routine work as it combines excellent reproducibility with strong correlation to unidirectional iodide clearance as the relevant parameter of thyroidal stimulation.", "contents": "[Studies on the reliability of the 99mTc-uptake as a measure of thyroidal stimulation (author's transl)]. In 44 patients with stimulated goitre the trapping kinetics of 131I-iodide and 99mTc-pertechnetate are analyzed having corrected for different size of the thyroid and different physical properties of the tracers under use. Unidirectional iodide clearance (UDCL) is chosen as reliable estimator of thyroidal stimulation. UDCL shows strong correlation to iodide uptake tests and the correlation to pertechnetate uptake tests is sufficiently strong for semiquantitative evaluation of thyroidal stimulation. Under the conditions of clinical routine work the reproducibility of pertechnetate uptake tests exceeds that of iodide, thus, pertechnetate uptakes are more suitable for evaluation of regulation tests, i.e. suppression test and stimulation test with TSH. 99mTc-thyroid-uptake (TcTU) 20 min after injection is a useful parameter of thyroidal stimulation for clinical routine work as it combines excellent reproducibility with strong correlation to unidirectional iodide clearance as the relevant parameter of thyroidal stimulation."} {"id": "PMID:160384", "title": "[\"Cold lesions\" in bone scintigraphy (author's transl)].", "content": "Frequency and location of \"cold lesions\" has been analysed in 1000 consecutive bone scans. Among the 554 abnormal cases there were 18 (1,8% of the total) with localized diminished activity due to metastatic lesions and 5 (0,5%) secondary to radiation osteitis. 10 of the 18 patients with metastatic disease had pure defects while 8 showed a reactive margin. It is pointed out that the quality of the examination is crucial for the demonstration of such defects and that single scans of the different regions of the skeleton are superior to a whole body scan. The survey of the literature shows that \"cold lesions\" are predominant in malignant bone diseases, however no relation exists to a definite histology.", "contents": "[\"Cold lesions\" in bone scintigraphy (author's transl)]. Frequency and location of \"cold lesions\" has been analysed in 1000 consecutive bone scans. Among the 554 abnormal cases there were 18 (1,8% of the total) with localized diminished activity due to metastatic lesions and 5 (0,5%) secondary to radiation osteitis. 10 of the 18 patients with metastatic disease had pure defects while 8 showed a reactive margin. It is pointed out that the quality of the examination is crucial for the demonstration of such defects and that single scans of the different regions of the skeleton are superior to a whole body scan. The survey of the literature shows that \"cold lesions\" are predominant in malignant bone diseases, however no relation exists to a definite histology."} {"id": "PMID:160385", "title": "[Estimation of 131I hippuran clearance during pregnancy (author's transl)].", "content": "Changes in 131I hippuran clearance were estimated by a non-catheter method, as well as total clearance and clearance of each kidney, in 43 women at various stages of pregnancy and in 13 non-pregnant women who were not using hormonal contraceptives. The results are demonstrated in graph form. The methods used are described in detail. The procedure for determining clearance in separate kidneys is indicated. It was found that clearance values increased up to the 35th and 36th weeks of pregnancy. The difference between the sides that were found corresponds with the previously known difference in the function of the right and left kidneys and ureters.", "contents": "[Estimation of 131I hippuran clearance during pregnancy (author's transl)]. Changes in 131I hippuran clearance were estimated by a non-catheter method, as well as total clearance and clearance of each kidney, in 43 women at various stages of pregnancy and in 13 non-pregnant women who were not using hormonal contraceptives. The results are demonstrated in graph form. The methods used are described in detail. The procedure for determining clearance in separate kidneys is indicated. It was found that clearance values increased up to the 35th and 36th weeks of pregnancy. The difference between the sides that were found corresponds with the previously known difference in the function of the right and left kidneys and ureters."} {"id": "PMID:160393", "title": "Influence of age on the sensitivity of the rat to streptozotocin.", "content": "The relationship between age and sensitivity to the diabetogenic effect of streptozotocin was investigated. Changes in the serum levels of several parameters (glucose, immunoreactive insulin, lipids), as well as changes of the pancreatic insulin content were monitored at 2, 4, 8, 24 and 48 h after the intravenous administration of different doses of streptozotocin in rats of various weights. Different concentrations of blood glucose and lipid and different amounts of pancreatic immunoreactive insulin could be found in rats of different ages 24 and 48 h after injection of the same dose of the drug (in mg/kg body weight). Also, age-dependent changes of serum immunoreactive insulin could be observed as early as 4 h after streptozotocin administration. All these changes indicate that the sensitivity of the rat to the diabetogenic effect of streptozotocin is inversely related to the age of the animals. Most likely, age-dependent pancreatic factors have an important role. In fact, the changes of the minimum dose of streptozotocin required to cause diabetes in rats of different weights closely parallel the age-related changes of the total immunoreactive insulin content of the pancreas of the intact rats. The role of other age-related factors which may influence the effectiveness of streptozotocin action is briefly discussed.", "contents": "Influence of age on the sensitivity of the rat to streptozotocin. The relationship between age and sensitivity to the diabetogenic effect of streptozotocin was investigated. Changes in the serum levels of several parameters (glucose, immunoreactive insulin, lipids), as well as changes of the pancreatic insulin content were monitored at 2, 4, 8, 24 and 48 h after the intravenous administration of different doses of streptozotocin in rats of various weights. Different concentrations of blood glucose and lipid and different amounts of pancreatic immunoreactive insulin could be found in rats of different ages 24 and 48 h after injection of the same dose of the drug (in mg/kg body weight). Also, age-dependent changes of serum immunoreactive insulin could be observed as early as 4 h after streptozotocin administration. All these changes indicate that the sensitivity of the rat to the diabetogenic effect of streptozotocin is inversely related to the age of the animals. Most likely, age-dependent pancreatic factors have an important role. In fact, the changes of the minimum dose of streptozotocin required to cause diabetes in rats of different weights closely parallel the age-related changes of the total immunoreactive insulin content of the pancreas of the intact rats. The role of other age-related factors which may influence the effectiveness of streptozotocin action is briefly discussed."} {"id": "PMID:160395", "title": "Peritoneal exudate T lymphocytes with specificity to sheep red blood cells. III. High dose of antigen induces suppressor T cells which influence the appearance in exudates of effector T cells for delayed-type hypersensitivity and helper T cells for humoral immune responses.", "content": "Antisera produced in rabbits against adherent cells of rat alveolar or peritoneal lavage fluid (anti-rat alveolar macrophage sera, ARAMS, or anti-rat peritoneal macrophage sera, ARPMS) were used to detect antigenic differences between alveolar (AM) and peritoneal (PM) macrophages in an indirect membrane immunofluorescence (IMF) test. Of all sera tested, the IMF titres were higher with cells of that population which was used for immunization. These differences were found before and after exhaustive absorptions with insolubilized rat plasma, rat erythrocytes, and non-adherant rat kidney, spleen, thymus and bone marrow cells. The differences were not due to antigens specific for one of the macrophage populations, as demonstrated by cross-adsorption studies with macrophages of different localization. It is assumed that two or more macrophage specific antigenic determinants are present in different density in the two macrophage populations.", "contents": "Peritoneal exudate T lymphocytes with specificity to sheep red blood cells. III. High dose of antigen induces suppressor T cells which influence the appearance in exudates of effector T cells for delayed-type hypersensitivity and helper T cells for humoral immune responses. Antisera produced in rabbits against adherent cells of rat alveolar or peritoneal lavage fluid (anti-rat alveolar macrophage sera, ARAMS, or anti-rat peritoneal macrophage sera, ARPMS) were used to detect antigenic differences between alveolar (AM) and peritoneal (PM) macrophages in an indirect membrane immunofluorescence (IMF) test. Of all sera tested, the IMF titres were higher with cells of that population which was used for immunization. These differences were found before and after exhaustive absorptions with insolubilized rat plasma, rat erythrocytes, and non-adherant rat kidney, spleen, thymus and bone marrow cells. The differences were not due to antigens specific for one of the macrophage populations, as demonstrated by cross-adsorption studies with macrophages of different localization. It is assumed that two or more macrophage specific antigenic determinants are present in different density in the two macrophage populations."} {"id": "PMID:160396", "title": "Dengue virus-induced thymus-derived suppressor cells in the spleen of mice.", "content": "Adoptive transfer of spleen cells obtained from mice given three weekly i.p. doses of dengue type 2 virus (DV) suppressed DV antigen-specific antibody secretion as detected by the Jerne plaque technique. This suppression was produced by non-glass-adherent cells but not by glass-adherent cells. Immune spleen cells depleted of macrophages by carbonyl iron treatment had higher suppressor activity. Immune spleen cell homogenate could transfer the activity equally well. The immune spleen cells were separated into T and B lymphocytes by a nylon wool column. B lymphocytes had no suppressor activity; almost all the suppressor activity was present in T lymphocytes. Thus, macrophages and B lymphocytes had no suppressor activity; it was mediated by T lymphocytes through soluble factors.", "contents": "Dengue virus-induced thymus-derived suppressor cells in the spleen of mice. Adoptive transfer of spleen cells obtained from mice given three weekly i.p. doses of dengue type 2 virus (DV) suppressed DV antigen-specific antibody secretion as detected by the Jerne plaque technique. This suppression was produced by non-glass-adherent cells but not by glass-adherent cells. Immune spleen cells depleted of macrophages by carbonyl iron treatment had higher suppressor activity. Immune spleen cell homogenate could transfer the activity equally well. The immune spleen cells were separated into T and B lymphocytes by a nylon wool column. B lymphocytes had no suppressor activity; almost all the suppressor activity was present in T lymphocytes. Thus, macrophages and B lymphocytes had no suppressor activity; it was mediated by T lymphocytes through soluble factors."} {"id": "PMID:160402", "title": "Staphylococcal lung abscess and acute glomerulonephritis.", "content": "A patient with a staphylococcal lung abscess developed acute glomerulonephritis with clinical and pathological features typical of postinfectious glomerulonephritis. There was no evidence of streptococcal infection and the nephritis resolved following treatment of the abscess.", "contents": "Staphylococcal lung abscess and acute glomerulonephritis. A patient with a staphylococcal lung abscess developed acute glomerulonephritis with clinical and pathological features typical of postinfectious glomerulonephritis. There was no evidence of streptococcal infection and the nephritis resolved following treatment of the abscess."} {"id": "PMID:160403", "title": "[Contact urticaria].", "content": "Report of a 42 year old woman who had given up her profession as a hairdresser because of urticarial skin eruptions following contact with substances used during working. An open patch test showed after 30 min positive urticarial reactions against permanent wave solution, fixation solution, p-aminodiphenylamin, lanolin-alcohol and clioquinol.", "contents": "[Contact urticaria]. Report of a 42 year old woman who had given up her profession as a hairdresser because of urticarial skin eruptions following contact with substances used during working. An open patch test showed after 30 min positive urticarial reactions against permanent wave solution, fixation solution, p-aminodiphenylamin, lanolin-alcohol and clioquinol."} {"id": "PMID:160404", "title": "[Lupus miliaris disseminatus faciei].", "content": "Three typical cases of lupus miliaris disseminatus faciei are presented with emphasis on clinical and histological data. Pathogenesis, differential diagnosis and therapy are shortly discussed.", "contents": "[Lupus miliaris disseminatus faciei]. Three typical cases of lupus miliaris disseminatus faciei are presented with emphasis on clinical and histological data. Pathogenesis, differential diagnosis and therapy are shortly discussed."} {"id": "PMID:160407", "title": "Purification and chemical characterization of the rodlet layer of Neurospora crassa conidia.", "content": "The rodlet layer of Neurospora crassa macroconidia has been purified and chemically characterized. Sheets of rodlets were released from the conidial surface by vigorously shaking conidia in water. Conidia were removed by filtration and low-speed centrifugation, and the rodlets were recovered from the supernatant by high-speed centrifugation. The rodlet pellet comprised 1.9% of the initial dry weight. Chemical analysis was hampered by the insolubility of the rodlets. They were not solubilized by heating in various protein-denaturing buffers and were only partially dissolved by heating in 1 M NaOH at 100 degrees C for 5 min. Nevertheless, they were found to be largely composed of protein (91%, based on total nitrogen). The major amino acids in acid hydrolysates were aspartic acid, glycine, serine, alanine, half-cystine, and valine. Glucosamine was not detected in acid hydrolysates. The sulfur content was 2.5%, and this could be accounted for in half-cystine and methionine. Carbohydrate comprised just over 2%. The phosphorus content was 0.21%, of which less than one-third was accounted for in phospholipid. The total fatty acid content was 1.0%, most of which could be accounted for by the fatty acids of the phospholipids.", "contents": "Purification and chemical characterization of the rodlet layer of Neurospora crassa conidia. The rodlet layer of Neurospora crassa macroconidia has been purified and chemically characterized. Sheets of rodlets were released from the conidial surface by vigorously shaking conidia in water. Conidia were removed by filtration and low-speed centrifugation, and the rodlets were recovered from the supernatant by high-speed centrifugation. The rodlet pellet comprised 1.9% of the initial dry weight. Chemical analysis was hampered by the insolubility of the rodlets. They were not solubilized by heating in various protein-denaturing buffers and were only partially dissolved by heating in 1 M NaOH at 100 degrees C for 5 min. Nevertheless, they were found to be largely composed of protein (91%, based on total nitrogen). The major amino acids in acid hydrolysates were aspartic acid, glycine, serine, alanine, half-cystine, and valine. Glucosamine was not detected in acid hydrolysates. The sulfur content was 2.5%, and this could be accounted for in half-cystine and methionine. Carbohydrate comprised just over 2%. The phosphorus content was 0.21%, of which less than one-third was accounted for in phospholipid. The total fatty acid content was 1.0%, most of which could be accounted for by the fatty acids of the phospholipids."} {"id": "PMID:160405", "title": "In vitro tests of cellular immunity in man.", "content": "There has been a recent rapid increase in the number of assays for cellular immunity in man and in information related to the mechanisms underlying the observed reactions. These tests have been applied clinically for three main purposes: (a) Evaluation of cell-mediated immune competence of patients with primary immune deficiencies and of possible immunological depression associated with cancer or other diseases. (b) Determination of major differences in histocompatibility antigens which might be important in rejection of organ transplants. Some cellular immune assays have become part of the routine battery of assays used for immunological evaluation of potential donors and recipients. (c) Measurement of specific immune reactivity against antigens associated with a variety of diseases, including infectious diseases, autoimmune diseases and cancer.", "contents": "In vitro tests of cellular immunity in man. There has been a recent rapid increase in the number of assays for cellular immunity in man and in information related to the mechanisms underlying the observed reactions. These tests have been applied clinically for three main purposes: (a) Evaluation of cell-mediated immune competence of patients with primary immune deficiencies and of possible immunological depression associated with cancer or other diseases. (b) Determination of major differences in histocompatibility antigens which might be important in rejection of organ transplants. Some cellular immune assays have become part of the routine battery of assays used for immunological evaluation of potential donors and recipients. (c) Measurement of specific immune reactivity against antigens associated with a variety of diseases, including infectious diseases, autoimmune diseases and cancer."} {"id": "PMID:160408", "title": "Chemiosmotic coupling in Methanobacterium thermoautotrophicum: hydrogen-dependent adenosine 5'-triphosphate synthesis by subcellular particles.", "content": "Hydrogenase and the adenosine 5'-triphosphate (ATP) synthetase complex, two enzymes essential in ATP generation in Methanobacterium thermoautotrophicum, were localized in internal membrane systems as shown by cytochemical techniques. Membrane vesicles from this organism possessed hydrogenase and adenosine triphosphatase (ATPase) activity and synthesized ATP driven by hydrogen oxidation or a potassium gradient. ATP synthesis depended on anaerobic conditions and could be inhibited in membrane vesicles by uncouplers, nigericin, or the ATPase inhibitor N,N'-dicyclohexylcarbodiimide. The presence of an adenosine 5'-diphosphate-ATP translocase was postulated. With fluorescent dyes, a membrane potential and pH gradient were demonstrated.", "contents": "Chemiosmotic coupling in Methanobacterium thermoautotrophicum: hydrogen-dependent adenosine 5'-triphosphate synthesis by subcellular particles. Hydrogenase and the adenosine 5'-triphosphate (ATP) synthetase complex, two enzymes essential in ATP generation in Methanobacterium thermoautotrophicum, were localized in internal membrane systems as shown by cytochemical techniques. Membrane vesicles from this organism possessed hydrogenase and adenosine triphosphatase (ATPase) activity and synthesized ATP driven by hydrogen oxidation or a potassium gradient. ATP synthesis depended on anaerobic conditions and could be inhibited in membrane vesicles by uncouplers, nigericin, or the ATPase inhibitor N,N'-dicyclohexylcarbodiimide. The presence of an adenosine 5'-diphosphate-ATP translocase was postulated. With fluorescent dyes, a membrane potential and pH gradient were demonstrated."} {"id": "PMID:160409", "title": "Siderophore synthesis in Klebsiella pneumoniae and Shigella sonnei during iron deficiency.", "content": "Klebsiella pneumoniae 298/53 and Shigella sonnei 43-GG9 exhibited restricted growth and enterochelin synthesis only under iron-deficient conditions. S. sonnei also produced an unidentified secondary hydroxamate siderophore.", "contents": "Siderophore synthesis in Klebsiella pneumoniae and Shigella sonnei during iron deficiency. Klebsiella pneumoniae 298/53 and Shigella sonnei 43-GG9 exhibited restricted growth and enterochelin synthesis only under iron-deficient conditions. S. sonnei also produced an unidentified secondary hydroxamate siderophore."} {"id": "PMID:160410", "title": "Isolation of Neurospora crassa bradytrophs.", "content": "A method was developed for the isolation of Neurospora bradytrophs. The bradytrophs (representing lesions in a number of pathways) were resistant to DL-p-fluorophenylalanine when growing in a leaky fashion but were sensitive when grown in the presence of their stimulating supplement.", "contents": "Isolation of Neurospora crassa bradytrophs. A method was developed for the isolation of Neurospora bradytrophs. The bradytrophs (representing lesions in a number of pathways) were resistant to DL-p-fluorophenylalanine when growing in a leaky fashion but were sensitive when grown in the presence of their stimulating supplement."} {"id": "PMID:160411", "title": "Response to a metal ion-citrate complex in bacterial sensing.", "content": "Salmonella typhimurium responds chemotactically to gradients of divalent cations in the presence of citrate ions. The actual chemoeffector is the citrate-metal ion complex, which acts as an attractant. Citrate (which is also a chemoeffector for Salmonella) and the citrate-metal ion complex are recognized by different receptors. The response of Salmonells, which can transport citrate through its membrane, is quite different than that of Escherichia coli, which cannot.", "contents": "Response to a metal ion-citrate complex in bacterial sensing. Salmonella typhimurium responds chemotactically to gradients of divalent cations in the presence of citrate ions. The actual chemoeffector is the citrate-metal ion complex, which acts as an attractant. Citrate (which is also a chemoeffector for Salmonella) and the citrate-metal ion complex are recognized by different receptors. The response of Salmonells, which can transport citrate through its membrane, is quite different than that of Escherichia coli, which cannot."} {"id": "PMID:160412", "title": "Cloning and physical mapping of the dnaA region of the Escherichia coli chromosome.", "content": "The dnaA gene of Escherichia coli K-12, supposedly present in the deoxyribonucleic acid (DNA) of specialized transducing phase lambda i21 dnaA-2, was cloned onto plasmid pBR322. The new plasmid was named pMCR501. Physical analyses of DNAs of lambda i21 dnaA-2 and pMCR501 revealed the following. The lambda i21 dnaA-2 DNA retained the delta sr I lambda 1-2 and ninR5 deletions and imm21 substitution which were originally present in the parental phage. The size reduction was compensated for by the insertion-substitution segment (tna-dnaA region) in lambda i21 dnaA-2 DNA. The fractional size of this segment was approximately 7 megadaltons (Md), or 10 kilobases, which was found to be the sum of the tna insertion subsegment of ca. 3.5 Md and the dnaA substitution subsegment of ca. 3.5 Md. Phage P1-mediated transductional mapping between the dnaA46 and tna mutations gave a cotransduction frequency of 84%, corresponding to approximately 5 kilobases. Thus, it is strongly suggested that the dnaA gene resides in the lambda i21 dnaA-2 DNA. Cleavage mapping with the restriction endonuclease of pMCR501 DNA confirmed that it was constructed by excising a BamHI fragment of 4.29 Md, containing the 3.5-Md dnaA substitution segment, from the lambda i21 dnaA-2 DNA, inserting it into the sole BamHI cleavage site on pBR322.", "contents": "Cloning and physical mapping of the dnaA region of the Escherichia coli chromosome. The dnaA gene of Escherichia coli K-12, supposedly present in the deoxyribonucleic acid (DNA) of specialized transducing phase lambda i21 dnaA-2, was cloned onto plasmid pBR322. The new plasmid was named pMCR501. Physical analyses of DNAs of lambda i21 dnaA-2 and pMCR501 revealed the following. The lambda i21 dnaA-2 DNA retained the delta sr I lambda 1-2 and ninR5 deletions and imm21 substitution which were originally present in the parental phage. The size reduction was compensated for by the insertion-substitution segment (tna-dnaA region) in lambda i21 dnaA-2 DNA. The fractional size of this segment was approximately 7 megadaltons (Md), or 10 kilobases, which was found to be the sum of the tna insertion subsegment of ca. 3.5 Md and the dnaA substitution subsegment of ca. 3.5 Md. Phage P1-mediated transductional mapping between the dnaA46 and tna mutations gave a cotransduction frequency of 84%, corresponding to approximately 5 kilobases. Thus, it is strongly suggested that the dnaA gene resides in the lambda i21 dnaA-2 DNA. Cleavage mapping with the restriction endonuclease of pMCR501 DNA confirmed that it was constructed by excising a BamHI fragment of 4.29 Md, containing the 3.5-Md dnaA substitution segment, from the lambda i21 dnaA-2 DNA, inserting it into the sole BamHI cleavage site on pBR322."} {"id": "PMID:160413", "title": "Conditionally lethal amber mutations in the dnaA region of the Escherichia coli chromosome that affect chromosome replication.", "content": "Three amber mutations, dna-801, dna-803, and dna-806, were isolated by localized mutagenesis of the dnaA-oriC region of the chromosome from an Escherichia coli strain carrying temperature-sensitive amber suppressors. When the mutations were not suppressed at 42 degrees C, the cells did not grow and DNA synthesis was arrested. They were very closely linked to each other and to the dnaA46 mutation. The mutant phenotype of each strain was converted to the wild type by infecting the mutants with specialized transducing phase lambda i21 dnaA-2 but not with lambda i21 tna. Derivatives of lambda i21 dnaA-2, each of which carried the amber mutation dna-801 dna-803, or dna-806, converted the dnaA mutant phenotype to Dna+ but did not convert rhe amber mutants to the wild-type phenotype. E. coli uvrB cells were irradiated with ultraviolet light and infected with each of these phage strains. An analysis of proteins synthesized in the cells revealed that two proteins with molecular weights of 50,000 and 43,000 were specified by lambda i21 dnaA-2 but not by lambda i21 tna. When the ultraviolet-irradiated cells did not carry an amber suppressor, the derivative phage with the amber mutation invariably failed to produce the 43,000-dalton protein, but when the host cell carried supF (tyrT), the protein was produced. The 50,000-dalton protein was unaffected.", "contents": "Conditionally lethal amber mutations in the dnaA region of the Escherichia coli chromosome that affect chromosome replication. Three amber mutations, dna-801, dna-803, and dna-806, were isolated by localized mutagenesis of the dnaA-oriC region of the chromosome from an Escherichia coli strain carrying temperature-sensitive amber suppressors. When the mutations were not suppressed at 42 degrees C, the cells did not grow and DNA synthesis was arrested. They were very closely linked to each other and to the dnaA46 mutation. The mutant phenotype of each strain was converted to the wild type by infecting the mutants with specialized transducing phase lambda i21 dnaA-2 but not with lambda i21 tna. Derivatives of lambda i21 dnaA-2, each of which carried the amber mutation dna-801 dna-803, or dna-806, converted the dnaA mutant phenotype to Dna+ but did not convert rhe amber mutants to the wild-type phenotype. E. coli uvrB cells were irradiated with ultraviolet light and infected with each of these phage strains. An analysis of proteins synthesized in the cells revealed that two proteins with molecular weights of 50,000 and 43,000 were specified by lambda i21 dnaA-2 but not by lambda i21 tna. When the ultraviolet-irradiated cells did not carry an amber suppressor, the derivative phage with the amber mutation invariably failed to produce the 43,000-dalton protein, but when the host cell carried supF (tyrT), the protein was produced. The 50,000-dalton protein was unaffected."} {"id": "PMID:160414", "title": "Inactivation of prophage in ultraviolet-irradiated Escherichia coli: dependence on recA gene activity.", "content": "The fate of the prophage part of the lysogenic chromosome was followed in the course of post-ultraviolet incubation. For this purpose, lambda cI857 ind prophage, which can be induced by heat but not by ultraviolet light, was used. The prophage, intially more resistant than its repair-proficient host cell, was rapidly inactivated. This inactivation was not caused by the impaired capacity of irradiated cells to support growth of the phage. Over the entire dose range tested, little, if any, sensitivity difference between the host and the prophage was found at the end of cell division delay. Rapid inactivation of the prophage was also observed in uvr cells after small doses of ultraviolet light. The same small doses did not cause inactivation in lysogens carrying a mutation in the gene recA. This suggests that the functional gene recA is required for inactivation of the prophage part of the lysogenic chromosome.", "contents": "Inactivation of prophage in ultraviolet-irradiated Escherichia coli: dependence on recA gene activity. The fate of the prophage part of the lysogenic chromosome was followed in the course of post-ultraviolet incubation. For this purpose, lambda cI857 ind prophage, which can be induced by heat but not by ultraviolet light, was used. The prophage, intially more resistant than its repair-proficient host cell, was rapidly inactivated. This inactivation was not caused by the impaired capacity of irradiated cells to support growth of the phage. Over the entire dose range tested, little, if any, sensitivity difference between the host and the prophage was found at the end of cell division delay. Rapid inactivation of the prophage was also observed in uvr cells after small doses of ultraviolet light. The same small doses did not cause inactivation in lysogens carrying a mutation in the gene recA. This suggests that the functional gene recA is required for inactivation of the prophage part of the lysogenic chromosome."} {"id": "PMID:160415", "title": "Immunochemical analysis of triton X-100-insoluble residues from Micrococcus lysodeikticus membranes.", "content": "Triton X-100-insoluble residues from Micrococcus lysodeikticus membranes were analyzed by crossed immunoelectrophoresis after dispersal of the residues in sodium dodecyl sulfate (SDS). Conditions which produce no obvious distortion of the immunoprecipitate profile and which allow qualitative and quantitative analyses of the antigens present in the extracts are described. Two main antigens were detected; these were identified as succinate dehydrogenase (EC 1.3.99.1) and adenosine triphosphatase (EC 3.6.1.3). As determined by peak area estimations, the maximal release of succinate dehydrogenase and of adenosine triphosphatase from Triton X-100-insoluble membrane residues occurred at protein/SDS ratios of about 4.3:1 (0.2% SDS) and 6.8:1 (0.13% SDS), respectively. A comparison of enzyme activities of SDS extracts with those of untreated, control Triton X-100-insoluble membrane residues indicated that both the succinate dehydrogenase and the adenosine triphosphatase antigens were released with a full (or enhanced) catalytic potential at or below concentrations of SDS required to effect maximal solubilization of the enzyme in question. Evidence is also presented to suggest that the more acidic of the two components detected by crossed immunoelectrophoresis for the heterogeneous adenosine triphosphatase antigen is more sensitive to SDS than is the other. Both succinate dehydrogenase and adenosine triphosphatase lost catalytic activity and were denatured at protein/SDS ratios lower than 3.4:1.", "contents": "Immunochemical analysis of triton X-100-insoluble residues from Micrococcus lysodeikticus membranes. Triton X-100-insoluble residues from Micrococcus lysodeikticus membranes were analyzed by crossed immunoelectrophoresis after dispersal of the residues in sodium dodecyl sulfate (SDS). Conditions which produce no obvious distortion of the immunoprecipitate profile and which allow qualitative and quantitative analyses of the antigens present in the extracts are described. Two main antigens were detected; these were identified as succinate dehydrogenase (EC 1.3.99.1) and adenosine triphosphatase (EC 3.6.1.3). As determined by peak area estimations, the maximal release of succinate dehydrogenase and of adenosine triphosphatase from Triton X-100-insoluble membrane residues occurred at protein/SDS ratios of about 4.3:1 (0.2% SDS) and 6.8:1 (0.13% SDS), respectively. A comparison of enzyme activities of SDS extracts with those of untreated, control Triton X-100-insoluble membrane residues indicated that both the succinate dehydrogenase and the adenosine triphosphatase antigens were released with a full (or enhanced) catalytic potential at or below concentrations of SDS required to effect maximal solubilization of the enzyme in question. Evidence is also presented to suggest that the more acidic of the two components detected by crossed immunoelectrophoresis for the heterogeneous adenosine triphosphatase antigen is more sensitive to SDS than is the other. Both succinate dehydrogenase and adenosine triphosphatase lost catalytic activity and were denatured at protein/SDS ratios lower than 3.4:1."} {"id": "PMID:160416", "title": "Analysis of the allosteric properties of rabbit muscle phosphofructokinase by means of affinity labeling with a reactive ATP analog.", "content": "A reactive ATP analog, N6-(6-bromoacetamidohexyl)-AMP-PCP, reacted specifically with the ATP inhibitory site of rabbit skeletal muscle phosphofructokinase without affecting the active site. Modification resulted in the incorporation of 1.01 mol of the reagent per mol of enzyme subunit. The modified enzyme was insensitive to allosteric inhibition by ATP and to activation by AMP at pH 7.2, where the native enzyme exhibits allosteric kinetic behavior. These observations demonstrate that we had succeeded in obtaining PFK fixed in the T state. Using the kinetic parameters of this modified enzyme, the kinetic properties of native enzyme can be quantitatively accounted for by the allosteric model of Monod-Wyman-Changeux. Further, the reagent was shown to have reacted with a specific cysteine residue near or at the ATP inhibitory site, and the sequence around the cysteine was determined as Cys-Lys-Asp-Phe-Arg.", "contents": "Analysis of the allosteric properties of rabbit muscle phosphofructokinase by means of affinity labeling with a reactive ATP analog. A reactive ATP analog, N6-(6-bromoacetamidohexyl)-AMP-PCP, reacted specifically with the ATP inhibitory site of rabbit skeletal muscle phosphofructokinase without affecting the active site. Modification resulted in the incorporation of 1.01 mol of the reagent per mol of enzyme subunit. The modified enzyme was insensitive to allosteric inhibition by ATP and to activation by AMP at pH 7.2, where the native enzyme exhibits allosteric kinetic behavior. These observations demonstrate that we had succeeded in obtaining PFK fixed in the T state. Using the kinetic parameters of this modified enzyme, the kinetic properties of native enzyme can be quantitatively accounted for by the allosteric model of Monod-Wyman-Changeux. Further, the reagent was shown to have reacted with a specific cysteine residue near or at the ATP inhibitory site, and the sequence around the cysteine was determined as Cys-Lys-Asp-Phe-Arg."} {"id": "PMID:160418", "title": "The effect of sarcomere length and stretching on the rate of ATP splitting in glycerinated rabbit psoas muscle fibers.", "content": "The effect of sarcomere length and stretching on the tension and the rate of ATP splitting was studied using small fiber bundles from glycerinated rabbit psoas muscle. The rate of ATP slitting was determined by measuring ADP production, while the tension development in response to a contracting solution (at pCa 5.3) was recorded in the same preparation. The isometric tension developed by the preparation decreased when the sarcomere length was increased. The decrease of tension development was accompanied by a decrease in the rate of ATP splitting. If a preparation exerting steady isometric tension was stretched by 5--10% at a velocity of 0.1 mm/s, the rate of ATP splitting was increased after stretching, while the steady isometric tension attained after stretching was also higher than the initial value. The extent of the excess ATP splitting caused by stretching decreased with increasing sarcomere length. These results suggest that the rate of the interaction cycle between actin and myosin molecules may increase as a result of stretching.", "contents": "The effect of sarcomere length and stretching on the rate of ATP splitting in glycerinated rabbit psoas muscle fibers. The effect of sarcomere length and stretching on the tension and the rate of ATP splitting was studied using small fiber bundles from glycerinated rabbit psoas muscle. The rate of ATP slitting was determined by measuring ADP production, while the tension development in response to a contracting solution (at pCa 5.3) was recorded in the same preparation. The isometric tension developed by the preparation decreased when the sarcomere length was increased. The decrease of tension development was accompanied by a decrease in the rate of ATP splitting. If a preparation exerting steady isometric tension was stretched by 5--10% at a velocity of 0.1 mm/s, the rate of ATP splitting was increased after stretching, while the steady isometric tension attained after stretching was also higher than the initial value. The extent of the excess ATP splitting caused by stretching decreased with increasing sarcomere length. These results suggest that the rate of the interaction cycle between actin and myosin molecules may increase as a result of stretching."} {"id": "PMID:160423", "title": "X-linked ichthyosis: a metabolic disease.", "content": "Sex-linked ichthyosis, a rather common genodermatosis, has recently been linked with deficiency of the enzyme steroid sulfatase. Data supporting this association and suggesting that alterations in lipid metabolism may cause abnormal keratinization are herein reviewed.", "contents": "X-linked ichthyosis: a metabolic disease. Sex-linked ichthyosis, a rather common genodermatosis, has recently been linked with deficiency of the enzyme steroid sulfatase. Data supporting this association and suggesting that alterations in lipid metabolism may cause abnormal keratinization are herein reviewed."} {"id": "PMID:160424", "title": "Rat strain differences in copulatory behavior after para-chlorophenylalanine and hormone treatment.", "content": "The potentiation of masculine copulatory behavior in castrated male rats following systemic para-chlorophenylalanine (PCPA) treatment was found to be dependent upon the strain of rat and the recency of castration. Wistar (W) and Sprague-Dawley (SD) males displayed a decline in behavioral responsiveness to PCPA treatment following castration, the W males retaining their behavioral responsiveness longer than SD males. Castrated W males were also behaviorally more responsive to androgen replacement than were SD males. Ovariectomized W and SD females receiving estrogen replacement displayed a strain difference in hormonal sensitivity. In tests for feminine copulatory behavior, ovariectomized W females were behaviorally more sensitive to estrogen treatment than SD females. Ovariectomized and estrogen-primed females of both strains displayed potentiated lordotic behavior following chronic PCPA treatment. Concomitant treatment with dexamethasone to reduce adrenal steroid output abolished the potentiation of lordotic behavior found with PCPA treatment.", "contents": "Rat strain differences in copulatory behavior after para-chlorophenylalanine and hormone treatment. The potentiation of masculine copulatory behavior in castrated male rats following systemic para-chlorophenylalanine (PCPA) treatment was found to be dependent upon the strain of rat and the recency of castration. Wistar (W) and Sprague-Dawley (SD) males displayed a decline in behavioral responsiveness to PCPA treatment following castration, the W males retaining their behavioral responsiveness longer than SD males. Castrated W males were also behaviorally more responsive to androgen replacement than were SD males. Ovariectomized W and SD females receiving estrogen replacement displayed a strain difference in hormonal sensitivity. In tests for feminine copulatory behavior, ovariectomized W females were behaviorally more sensitive to estrogen treatment than SD females. Ovariectomized and estrogen-primed females of both strains displayed potentiated lordotic behavior following chronic PCPA treatment. Concomitant treatment with dexamethasone to reduce adrenal steroid output abolished the potentiation of lordotic behavior found with PCPA treatment."} {"id": "PMID:160425", "title": "Seborrheic keratoses and trichostasis spinulosa.", "content": "In 54 of 325 seborrheic keratoses, trichostasis spinulosa was found within the keratinous cysts and between papillomatous surface keratin, in addition to being present in contiguous hair follicles. Trichostasis in seborrheic keratoses and trichostasis spinulosa are both more frequent in older age groups. Trichostasis spinulosa represents a marker of vellus hair follicles and indicates that some seborrheic keratoses incorporate and may be partially derived from the cells of the infundibular portion of the follicle.", "contents": "Seborrheic keratoses and trichostasis spinulosa. In 54 of 325 seborrheic keratoses, trichostasis spinulosa was found within the keratinous cysts and between papillomatous surface keratin, in addition to being present in contiguous hair follicles. Trichostasis in seborrheic keratoses and trichostasis spinulosa are both more frequent in older age groups. Trichostasis spinulosa represents a marker of vellus hair follicles and indicates that some seborrheic keratoses incorporate and may be partially derived from the cells of the infundibular portion of the follicle."} {"id": "PMID:160435", "title": "Ultrastructural cytochemical studies of plasma membrane phosphatase activities during the HeLa S3 cell cycle.", "content": "Alkaline phosphatase (AP), 5'-nucleotidase (5'N), Mg2+-activated ATPase (Mg-ATPase) and Ca2+-activated ATPase (Ca-ATPase) were studied in sychronized HeLa S3 cells with cytochemical methods and electron microscopy. It was found that AP activity, as determined by the deposition of lead phosphate reaction product (r.p.) was most active in mitotic (M), early and middle G1 cells, less active in late G1 and almost undetectable in S phase cells. Most AP enzyme activity was found to be associated with undulations (mainly microvilli) of the plasma membrane. Fluctuations and the redistribution of 5'N were also observed; the reaction for 5'N was positive in all phases of the cell cycle studied, it was strongest in M cells and in the majority of middle G1 cells. Mg-ATPase activity was present in the plasma membranes of cells throughout the cell cycle, but did not show noticeable fluctuations in activity and distribution. Ca-ATPase activity appeared in plasma membranes and in limited areas of cell nuclei but was evident only in S phase cells. The results of the present study confirm and extend previous biochemical observations and indicate that changes in membrane phosphate activities are associated with enzyme activity redistributions within the plasma membrane during the HeLa S3 cell cycle.", "contents": "Ultrastructural cytochemical studies of plasma membrane phosphatase activities during the HeLa S3 cell cycle. Alkaline phosphatase (AP), 5'-nucleotidase (5'N), Mg2+-activated ATPase (Mg-ATPase) and Ca2+-activated ATPase (Ca-ATPase) were studied in sychronized HeLa S3 cells with cytochemical methods and electron microscopy. It was found that AP activity, as determined by the deposition of lead phosphate reaction product (r.p.) was most active in mitotic (M), early and middle G1 cells, less active in late G1 and almost undetectable in S phase cells. Most AP enzyme activity was found to be associated with undulations (mainly microvilli) of the plasma membrane. Fluctuations and the redistribution of 5'N were also observed; the reaction for 5'N was positive in all phases of the cell cycle studied, it was strongest in M cells and in the majority of middle G1 cells. Mg-ATPase activity was present in the plasma membranes of cells throughout the cell cycle, but did not show noticeable fluctuations in activity and distribution. Ca-ATPase activity appeared in plasma membranes and in limited areas of cell nuclei but was evident only in S phase cells. The results of the present study confirm and extend previous biochemical observations and indicate that changes in membrane phosphate activities are associated with enzyme activity redistributions within the plasma membrane during the HeLa S3 cell cycle."} {"id": "PMID:160436", "title": "Inhibition of MLC stimulator function by antibodies directed to non-HLA antigens.", "content": "The properties of five human alloantisera which inhibit the stimulating capacity of cells in an MLC reactions are described. All of the sera showed patterns of inhibition in families which did not correlate with HLA haplotypes. In a large proportion of the families investigated the sera did not react with parental cells but inhibited the cells from one or more of the children. Absorptions were performed with one of these sera using such non-reactive parental cells. Paternal cells absorbed out the inhibiting activity while maternal cells did not. This indicates that expression of the antigen with which the inhibiting antiserum reacts is insufficient for inhibition and other factors, either environmental or inherited from the mother, influence the capacity of the antiserum to cause inhibition. This antigen was most likely a non-HLA antigen.", "contents": "Inhibition of MLC stimulator function by antibodies directed to non-HLA antigens. The properties of five human alloantisera which inhibit the stimulating capacity of cells in an MLC reactions are described. All of the sera showed patterns of inhibition in families which did not correlate with HLA haplotypes. In a large proportion of the families investigated the sera did not react with parental cells but inhibited the cells from one or more of the children. Absorptions were performed with one of these sera using such non-reactive parental cells. Paternal cells absorbed out the inhibiting activity while maternal cells did not. This indicates that expression of the antigen with which the inhibiting antiserum reacts is insufficient for inhibition and other factors, either environmental or inherited from the mother, influence the capacity of the antiserum to cause inhibition. This antigen was most likely a non-HLA antigen."} {"id": "PMID:160442", "title": "The effect of 5-bromodeoxyuridine on interferon production in human cells.", "content": "5-Bromodeoxyuridine (BrdUrd) increased interferon production by the Namalwa line of human lymphoblastoid cells treated with Sendai virus, but inhibited their growth. Thymidine, which also inhibited cell growth had no effect on interferon production, so that growth inhibition per se was not the cause of the stimulation. BrdUrd was incorporated into cellular DNA; 5-chlorodeoxyuridine and 5-iododeoxyuridine (which are also incorporated) increased the interferon yield, but 5-fluorodeoxyuridine (which is not incorporated) did not. Thymidine reduced both the incorporation of BrdUrd and its stimulatory effect on interferon production. Deoxycytidine (which prevents the cytotoxic effects of BrdUrd) had no effect on the stimulation. BrdUrd also stimulated interferon production in response to poly(rI) . poly(rC) in growing human diploid fibroblasts but not in SV40 virus-transformed human cells. Since BrdUrd was incorporated into the DNA of all these cells, we concluded that incorporation is necessary, but not sufficient for the stimulation of interferon formation.", "contents": "The effect of 5-bromodeoxyuridine on interferon production in human cells. 5-Bromodeoxyuridine (BrdUrd) increased interferon production by the Namalwa line of human lymphoblastoid cells treated with Sendai virus, but inhibited their growth. Thymidine, which also inhibited cell growth had no effect on interferon production, so that growth inhibition per se was not the cause of the stimulation. BrdUrd was incorporated into cellular DNA; 5-chlorodeoxyuridine and 5-iododeoxyuridine (which are also incorporated) increased the interferon yield, but 5-fluorodeoxyuridine (which is not incorporated) did not. Thymidine reduced both the incorporation of BrdUrd and its stimulatory effect on interferon production. Deoxycytidine (which prevents the cytotoxic effects of BrdUrd) had no effect on the stimulation. BrdUrd also stimulated interferon production in response to poly(rI) . poly(rC) in growing human diploid fibroblasts but not in SV40 virus-transformed human cells. Since BrdUrd was incorporated into the DNA of all these cells, we concluded that incorporation is necessary, but not sufficient for the stimulation of interferon formation."} {"id": "PMID:160443", "title": "Transient global amnesia after clioquinol: five personal observations from outside Japan.", "content": "Five personal observations of an acute amnestic episode in younger individuals after intake of clioquinol are described together with three observations from the medical literature. In five of these cases the episode began after an unusually large dose, in three after a therapeutic one with a latency of about 24 hours. The clinical aspect closely resembled classical transient global amnesia but the episode after clioquinol lasted longer (24 hours to three days) and a more or less extensive retrograde amnesia persisted permanently. In one patient after three tablets of Mexase a clioquinol concentration of 12 microgram/ml in plasma was found 24 hours after the specified dose, which is an unexpectedly high concentration compared to those reported as late as 24 hours after a single equal dose of Mexase or any other clioquinol-containing preparation. Another patient had a brief relapse two years after the first episode, after a single therapeutic dose of another clioquinol preparation.", "contents": "Transient global amnesia after clioquinol: five personal observations from outside Japan. Five personal observations of an acute amnestic episode in younger individuals after intake of clioquinol are described together with three observations from the medical literature. In five of these cases the episode began after an unusually large dose, in three after a therapeutic one with a latency of about 24 hours. The clinical aspect closely resembled classical transient global amnesia but the episode after clioquinol lasted longer (24 hours to three days) and a more or less extensive retrograde amnesia persisted permanently. In one patient after three tablets of Mexase a clioquinol concentration of 12 microgram/ml in plasma was found 24 hours after the specified dose, which is an unexpectedly high concentration compared to those reported as late as 24 hours after a single equal dose of Mexase or any other clioquinol-containing preparation. Another patient had a brief relapse two years after the first episode, after a single therapeutic dose of another clioquinol preparation."} {"id": "PMID:160444", "title": "Primary writing tremor.", "content": "We describe a patient who complained of jerking of the right forearm on writing. Active pronation of his arm produced several beats of pronation/supination tremor. A burst of tremor also could be elicited by tendon taps to the volar surface of the wrist, to the finger extensors, and to pectoralis major, and by forcible supination of the wrist delivered by a torque motor. The subject's writing difficulty and tremor were temporarily abolished by partial motor point anaesthesia of pronator teres. We conclude that the tremor was caused by an abnormal response to muscle spindle input from pronator teres.", "contents": "Primary writing tremor. We describe a patient who complained of jerking of the right forearm on writing. Active pronation of his arm produced several beats of pronation/supination tremor. A burst of tremor also could be elicited by tendon taps to the volar surface of the wrist, to the finger extensors, and to pectoralis major, and by forcible supination of the wrist delivered by a torque motor. The subject's writing difficulty and tremor were temporarily abolished by partial motor point anaesthesia of pronator teres. We conclude that the tremor was caused by an abnormal response to muscle spindle input from pronator teres."} {"id": "PMID:160445", "title": "Interactions between central monoaminergic systems: dopamine-serotonin.", "content": "Concentration of dopamine and serotonin metabolites (HVA and 5-HIAA) in the CSF was evaluated before and after pharmacological treatment in 19 patients with different neuropsychiatric diseases. In every case a reciprocal modification of the two metabolites occurred after treatment. The result supports the hypothesis of a functional balance between the monoaminergic systems in the central nervous system.", "contents": "Interactions between central monoaminergic systems: dopamine-serotonin. Concentration of dopamine and serotonin metabolites (HVA and 5-HIAA) in the CSF was evaluated before and after pharmacological treatment in 19 patients with different neuropsychiatric diseases. In every case a reciprocal modification of the two metabolites occurred after treatment. The result supports the hypothesis of a functional balance between the monoaminergic systems in the central nervous system."} {"id": "PMID:160446", "title": "An evaluation of some carrier detection techniques in Duchenne muscular dystrophy.", "content": "Some recently described abnormalities in the serum and red cell membranes in Duchenne dystrophy have been examined as methods of carrier detection in a single-blind controlled study. Twelve carriers (4 definite, 3 probable and 5 possible carriers previously found to have raised creatine kinase levels) and 12 normal female controls of the same age, were examined on 3 separate occasions at approximately two-weekly intervals. Analysis of age-dependent red cell shape changes, serum haemopexin levels, red cell K+ efflux rate, sensitivity of red cell ghost membrane ATPase to ouabain, membrane protein phosphorylation studies and lactate dehydrogenase isoenzyme profiles on agarose gel electrohoresis all failed to distinquish carriers from controls. The carriers suffered muscle cramps more frequently than the controls and all but one carrier and two control subjects were correctly identified by manual muscle strength testing, certain proximal muscles in paricular being consistently weaker in carriers than in the control group subjects. Scalar electrocardiography revealed higher values for the R/S ratio in Leads V1 and V2 and the sum (R-S) in V2.", "contents": "An evaluation of some carrier detection techniques in Duchenne muscular dystrophy. Some recently described abnormalities in the serum and red cell membranes in Duchenne dystrophy have been examined as methods of carrier detection in a single-blind controlled study. Twelve carriers (4 definite, 3 probable and 5 possible carriers previously found to have raised creatine kinase levels) and 12 normal female controls of the same age, were examined on 3 separate occasions at approximately two-weekly intervals. Analysis of age-dependent red cell shape changes, serum haemopexin levels, red cell K+ efflux rate, sensitivity of red cell ghost membrane ATPase to ouabain, membrane protein phosphorylation studies and lactate dehydrogenase isoenzyme profiles on agarose gel electrohoresis all failed to distinquish carriers from controls. The carriers suffered muscle cramps more frequently than the controls and all but one carrier and two control subjects were correctly identified by manual muscle strength testing, certain proximal muscles in paricular being consistently weaker in carriers than in the control group subjects. Scalar electrocardiography revealed higher values for the R/S ratio in Leads V1 and V2 and the sum (R-S) in V2."} {"id": "PMID:160447", "title": "Association of myocardial cell necrosis with experimental cardiac hypertrophy.", "content": "Cardiac hypertrophy was induced in rabbits by injecting thyroxine or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.", "contents": "Association of myocardial cell necrosis with experimental cardiac hypertrophy. Cardiac hypertrophy was induced in rabbits by injecting thyroxine or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart."} {"id": "PMID:160450", "title": "[Pericardial effusions (85 cases): radiological aspects (author's transl)].", "content": "A radiological study of 85 patients with acute pericarditis and effusion included a group of 35 cases observed before the introduction of ultrasonography and a second group of 50 patients in whom the presence of pericarditis had been confirmed by this investigation. The most important conclusions established were the following: --Absence of radiological signs in 55% of cases (group 1 : 46%, group 2 : 60%); normal heart size in 54% (group 1) and 78% (group 2), and increased size in 34% (group 1) and 20% (group 2). --Hilar manifestations (overlapping and obscuring of the left hilar region) in 26% of cases with a clear predominence of the left forms (14 out of 22). The cardiomegaly was not significant in 28% (group 1) and 14% (group 2). --The high frequency of pericarditis with a normal heart size has to be emphasized. The diagnostic value of hilar manifestations is also mentioned; the sign of left hilar overlapping is described in greater detail. --An overall comparison between the two groups shows, more particularly, the equal importance of left hilar manifestations for the radiological diagnosis of pericarditis. In a general way, it would appear that these hilar signs are the only elements which enable objective diagnosis of pericardial effusions on standard films.", "contents": "[Pericardial effusions (85 cases): radiological aspects (author's transl)]. A radiological study of 85 patients with acute pericarditis and effusion included a group of 35 cases observed before the introduction of ultrasonography and a second group of 50 patients in whom the presence of pericarditis had been confirmed by this investigation. The most important conclusions established were the following: --Absence of radiological signs in 55% of cases (group 1 : 46%, group 2 : 60%); normal heart size in 54% (group 1) and 78% (group 2), and increased size in 34% (group 1) and 20% (group 2). --Hilar manifestations (overlapping and obscuring of the left hilar region) in 26% of cases with a clear predominence of the left forms (14 out of 22). The cardiomegaly was not significant in 28% (group 1) and 14% (group 2). --The high frequency of pericarditis with a normal heart size has to be emphasized. The diagnostic value of hilar manifestations is also mentioned; the sign of left hilar overlapping is described in greater detail. --An overall comparison between the two groups shows, more particularly, the equal importance of left hilar manifestations for the radiological diagnosis of pericarditis. In a general way, it would appear that these hilar signs are the only elements which enable objective diagnosis of pericardial effusions on standard films."} {"id": "PMID:160451", "title": "Historical predictability of abnormal laparoscopic findings in the infertile woman.", "content": "The conventional approach to laparoscopy in an infertility workup has been to perform the procedure in the latter stages. Alternative ways have been suggested. Our investigation attempted to assess the suitabilities of an alternative approach. The laparoscopic findings in a group of 231 patients examined as part of an infertility workup have been analyzed. The predictability of abnormal findings has been demonstrated with accuracy in those patients with certain symptomatic or historical associations. The ability to predict abnormalities would suggest that laparoscopy should be performed early in the workup in this group. This holds true regardless of the discovery of any other abnormality which might be thought to be related to the patient's infertility.", "contents": "Historical predictability of abnormal laparoscopic findings in the infertile woman. The conventional approach to laparoscopy in an infertility workup has been to perform the procedure in the latter stages. Alternative ways have been suggested. Our investigation attempted to assess the suitabilities of an alternative approach. The laparoscopic findings in a group of 231 patients examined as part of an infertility workup have been analyzed. The predictability of abnormal findings has been demonstrated with accuracy in those patients with certain symptomatic or historical associations. The ability to predict abnormalities would suggest that laparoscopy should be performed early in the workup in this group. This holds true regardless of the discovery of any other abnormality which might be thought to be related to the patient's infertility."} {"id": "PMID:160452", "title": "Ketamine--HCl--diazepam anesthesia for laparoscopy.", "content": "Laparoscopy was performed on 150 patients under ketamine-HCl-diazepam anesthesia via intravenous drip infusion. No psychomotor disturbances were noted during the emergence phase. No complications occurred during the procedures, neither from the surgical nor from the anesthesiologic point of view. No alarming stimulation of the cardiovascular system was noted. The patients became responsive within a short time, but a state of strong sleepiness remained for several hours. Therefore, ketamine-HCl-diazepam anesthesia does not appear suitable for outpatient laparoscopies but is a valuable alternative to other methods of anesthesia for laparoscopy.", "contents": "Ketamine--HCl--diazepam anesthesia for laparoscopy. Laparoscopy was performed on 150 patients under ketamine-HCl-diazepam anesthesia via intravenous drip infusion. No psychomotor disturbances were noted during the emergence phase. No complications occurred during the procedures, neither from the surgical nor from the anesthesiologic point of view. No alarming stimulation of the cardiovascular system was noted. The patients became responsive within a short time, but a state of strong sleepiness remained for several hours. Therefore, ketamine-HCl-diazepam anesthesia does not appear suitable for outpatient laparoscopies but is a valuable alternative to other methods of anesthesia for laparoscopy."} {"id": "PMID:160455", "title": "HLA B27 in patients with seronegative spondarthritides.", "content": "We investigated the pattern of genetic susceptibility to rheumatic diseases in Indians by means of HLA analysis. HLA B27 was present in more than 90% of cases included under the broad category or seronegative spondarthritides. In this respect our data resembled results reported for Caucasian populations. In our population, however, the phenotypic frequency of HLA B27 was low as reported from Japan.", "contents": "HLA B27 in patients with seronegative spondarthritides. We investigated the pattern of genetic susceptibility to rheumatic diseases in Indians by means of HLA analysis. HLA B27 was present in more than 90% of cases included under the broad category or seronegative spondarthritides. In this respect our data resembled results reported for Caucasian populations. In our population, however, the phenotypic frequency of HLA B27 was low as reported from Japan."} {"id": "PMID:160456", "title": "Tomographic examinations of sacroiliac joints in adult patients with rheumatoid arthritis.", "content": "Tomography of the sacroiliac joints (SIJ) was performed in 72 patients with rheumatoid arthritis (RA) and in 50 controls. Twenty-seven rheumatoid patients (38%) showed typical sacroilitis with predominantly severe intraarticular ankylosis and subchondral erosions. Fourteen patients (19%) had a probable sacroilitis with mild erosions and intraarticular ankylosis and concomitant degenerative changes. Fifteen patients (21%) showed predominantly degenerative changes and 16 RA patients (22%) had no radiological manifestation of the SIJ. There was no relation between typical sacroilitis and age of patients, duration of disease, rheumatoid factor, Steinbrocker's stage and frequency of HLA B27.", "contents": "Tomographic examinations of sacroiliac joints in adult patients with rheumatoid arthritis. Tomography of the sacroiliac joints (SIJ) was performed in 72 patients with rheumatoid arthritis (RA) and in 50 controls. Twenty-seven rheumatoid patients (38%) showed typical sacroilitis with predominantly severe intraarticular ankylosis and subchondral erosions. Fourteen patients (19%) had a probable sacroilitis with mild erosions and intraarticular ankylosis and concomitant degenerative changes. Fifteen patients (21%) showed predominantly degenerative changes and 16 RA patients (22%) had no radiological manifestation of the SIJ. There was no relation between typical sacroilitis and age of patients, duration of disease, rheumatoid factor, Steinbrocker's stage and frequency of HLA B27."} {"id": "PMID:160461", "title": "Usnic acid derivatives as potential antineoplastic agents.", "content": "Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system. In an effort to produce new agents of potential use in the treatment of lung cancer, derivatives of the natural product were synthesized and evaluated with a cytotoxicity assay. Structure--activity analysis of the cytotoxicity data indicated the importance of the lipophilicity and the beta-triketone moiety of usnic acid on cytotoxicity. No significant increases in survival of test animals over controls were shown by any of the synthetic compounds in the P388 leukemia or the Lewis lung carcinoma test systems.", "contents": "Usnic acid derivatives as potential antineoplastic agents. Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system. In an effort to produce new agents of potential use in the treatment of lung cancer, derivatives of the natural product were synthesized and evaluated with a cytotoxicity assay. Structure--activity analysis of the cytotoxicity data indicated the importance of the lipophilicity and the beta-triketone moiety of usnic acid on cytotoxicity. No significant increases in survival of test animals over controls were shown by any of the synthetic compounds in the P388 leukemia or the Lewis lung carcinoma test systems."} {"id": "PMID:160458", "title": "Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by corticosteroids: further evidence for the presence and pathogenetic role of two populations of splenic suppressor cells.", "content": "This study confirms observations that active adjuvant-induced disease is accompanied by diminished spleen cell responses to phytohemagglutinin and concanavalin A; and that these diminished responses are due to suppressor cells, some adherent only to glass, and others adherent to plastic or glass. Corticosteroid inhibition of adjuvant disease is accompanied by a diminution or absence of these splenic suppressor cells. Some of these suppressor cells are inhibited in vitro by corticosteroids, in preference to the mitogen-responsive cells. This suggests that suppressor cells may play a role in the pathogenesis of AID.", "contents": "Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by corticosteroids: further evidence for the presence and pathogenetic role of two populations of splenic suppressor cells. This study confirms observations that active adjuvant-induced disease is accompanied by diminished spleen cell responses to phytohemagglutinin and concanavalin A; and that these diminished responses are due to suppressor cells, some adherent only to glass, and others adherent to plastic or glass. Corticosteroid inhibition of adjuvant disease is accompanied by a diminution or absence of these splenic suppressor cells. Some of these suppressor cells are inhibited in vitro by corticosteroids, in preference to the mitogen-responsive cells. This suggests that suppressor cells may play a role in the pathogenesis of AID."} {"id": "PMID:160462", "title": "Synthesis and antitumor properties of 7-deoxy-7-[(cis- and trans-3-aminocyclohexane)thio]carminomycinone.", "content": "The synthesis of analogues of carminomycin in which the daunosamine group has been replaced by (cis- and trans-3-aminocyclohexane)thio moieties is described. The new compounds were found to exhibit none of the antitumor or antibiotic activity associated with carminomycin.", "contents": "Synthesis and antitumor properties of 7-deoxy-7-[(cis- and trans-3-aminocyclohexane)thio]carminomycinone. The synthesis of analogues of carminomycin in which the daunosamine group has been replaced by (cis- and trans-3-aminocyclohexane)thio moieties is described. The new compounds were found to exhibit none of the antitumor or antibiotic activity associated with carminomycin."} {"id": "PMID:160459", "title": "Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by virazole: possible pathogenetic role of a virus and suppressor cells.", "content": "Adjuvant arthritis is inhibited by the interferon-inducing anti-viral agents statolon, pyran copolymer and tilorone, and by the passive transfer of interferon. The present experiments demonstrate that Virazole, a non-interferon-inducing, anti-viral agent also inhibits adjuvant arthritis. The responses of splenic lymphocytes to phytohemagglutinin and concanavalin A are diminished in active adjuvant disease, due to suppressor cells. Suppressor cells are absent during spontaneous, methodrexate or corticosteroid-induced remissions. Suppressor cells are also absent during Virazole-induced inhibition of adjuvant disease. Methotrexate and corticosteroids inhibit suppressor cells in preference to mitogen-responsive cells in vitro. The preferential inhibition with Virazole is superior to that noted with methotrexate or corticosteroids.", "contents": "Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by virazole: possible pathogenetic role of a virus and suppressor cells. Adjuvant arthritis is inhibited by the interferon-inducing anti-viral agents statolon, pyran copolymer and tilorone, and by the passive transfer of interferon. The present experiments demonstrate that Virazole, a non-interferon-inducing, anti-viral agent also inhibits adjuvant arthritis. The responses of splenic lymphocytes to phytohemagglutinin and concanavalin A are diminished in active adjuvant disease, due to suppressor cells. Suppressor cells are absent during spontaneous, methodrexate or corticosteroid-induced remissions. Suppressor cells are also absent during Virazole-induced inhibition of adjuvant disease. Methotrexate and corticosteroids inhibit suppressor cells in preference to mitogen-responsive cells in vitro. The preferential inhibition with Virazole is superior to that noted with methotrexate or corticosteroids."} {"id": "PMID:160468", "title": "Noninvasive Doppler ultrasound evaluation of aortocoronary bypass.", "content": "Using ultrasound method, aortocoronary bypass patency was determined by means of bidirectional Doppler's flowmeter. In 8 (3%) of 302 subjects without aortocoronary bypass was recorded diastolic signal which might distort the results of postoperative evaluation of graft patency. Two-hundred and ninety-seven patients with 330 aortocoronary bypasses were studied at the mean time of 8 months after operation. The graft patency was 84.5%. Comparison of 89 ultrasound findings with angiographic results established considerable specificity (90%) and sufficient sensitivity (77%). Reproducibility of this method was also good. The method is inexpensive and not time consuming. The advantages are also its safety and convenience for the patient. In the present level of development it can be used mainly as screening test at long-term follow-up of aortocoronary graft patency.", "contents": "Noninvasive Doppler ultrasound evaluation of aortocoronary bypass. Using ultrasound method, aortocoronary bypass patency was determined by means of bidirectional Doppler's flowmeter. In 8 (3%) of 302 subjects without aortocoronary bypass was recorded diastolic signal which might distort the results of postoperative evaluation of graft patency. Two-hundred and ninety-seven patients with 330 aortocoronary bypasses were studied at the mean time of 8 months after operation. The graft patency was 84.5%. Comparison of 89 ultrasound findings with angiographic results established considerable specificity (90%) and sufficient sensitivity (77%). Reproducibility of this method was also good. The method is inexpensive and not time consuming. The advantages are also its safety and convenience for the patient. In the present level of development it can be used mainly as screening test at long-term follow-up of aortocoronary graft patency."} {"id": "PMID:160469", "title": "Effects of 2-nicotinamidoethyl nitrate on the cardiovascular system.", "content": "Using the dog as experimental animal, effects on the cardiovascular system of a new vasodilator, 2-nicotinamidoethyl nitrate (SG-75), were studied. In the heart-lung preparation, the compound produced a dose-dependent increase in the coronary blood flow, which was associated with only a minimal increase in the myocardial oxygen consumption. There was essentially no change in the myocardial function. The myocardial redox potential was shifted to more positive values. In the isolated perfused heart preparation (Langendorff's preparation), SG-75 produced a dilatation of only the small resistive arterioles. However, it produced a dilatation of the large conductive artery in underperfused myocardium. SG-75 produced a significant increase in the cerebral venous outflow, associated with an increase in the cerebro-spinal fluid pressure. It produced a reducation of the venous return, which was especially prominent in the lower half of the body. In the isolated smooth muscle preparation of the coronary artery, high-doses of SG-75 induced calcium antagonistic effects and produced a relaxation of the lanthanum contracture.", "contents": "Effects of 2-nicotinamidoethyl nitrate on the cardiovascular system. Using the dog as experimental animal, effects on the cardiovascular system of a new vasodilator, 2-nicotinamidoethyl nitrate (SG-75), were studied. In the heart-lung preparation, the compound produced a dose-dependent increase in the coronary blood flow, which was associated with only a minimal increase in the myocardial oxygen consumption. There was essentially no change in the myocardial function. The myocardial redox potential was shifted to more positive values. In the isolated perfused heart preparation (Langendorff's preparation), SG-75 produced a dilatation of only the small resistive arterioles. However, it produced a dilatation of the large conductive artery in underperfused myocardium. SG-75 produced a significant increase in the cerebral venous outflow, associated with an increase in the cerebro-spinal fluid pressure. It produced a reducation of the venous return, which was especially prominent in the lower half of the body. In the isolated smooth muscle preparation of the coronary artery, high-doses of SG-75 induced calcium antagonistic effects and produced a relaxation of the lanthanum contracture."} {"id": "PMID:160471", "title": "[Some experiments on the allergic reaction among workers in a pharmaceutical factory (author's transl)].", "content": "A survey was made on workers handling powdered drugs in a pharmaceutical factory. In this factory, two kinds of anti-inflammatory enzyme (bromelain and trypsin), one anti-inflammatory agent (flufenamic acid), one antispasmodic (flopropion) and two kinds of antibiotics (ampicillin and cephalexin) are mainly produced. Twenty four workers were examined by interviews and checked by Cornell Medical Index, and 18 of them complained of respiratory symptoms. These 18 workers were physically examined by skin scratch tests, pulmonary function tests and serum immunological tests. Among 24 workers, 9 handled powdered drugs (A group), 5 handled the same in the past and had already been transferred to other sections for their symptoms (B group), 3 engaged in the process of capsul-filling (C group) and 7 handled several times occasionally during one year (D group). Their average months spent in handling powdered drugs were, in the case of anti-inflammatory enzyme, A group 53.2, B group 66.2, and in the case of antibiotics, 5 workers in A group 24.0, 2 workers in B group 7.0, 3 workers in C group 25.7. Twenty workers complained of symptoms which were mainly irritation of mucosa including the respiratory system and itching of the skin while they were working, and accelerated nasal discharge, urticaria and asthma after working. Group A and group B were higher than group D in the rate of respiratory complaints in C.M.I. (p less than 0.001). Fourteen workers pointed out anti-inflammatory enzyme as a cause of main symptoms, 7 workers flufenamic acid, 3 workers flopropion, 4 workers antibiotics. Three workers who had past history of asthma or articular rheumatism had been transferred to other sections. Of 18 workers who were physically examined, 11 workers showed positive reactions to skin scratch tests with handling drugs. On 8 workers of them, some kinds of drugs which were pointed out as drugs causing main symptoms reacted positively. Numbers of workers with increased immunoglobin values were, IgE 3, IgM 2, IgA 4, IgM 2. Two workers showed decreased FVC and FEV (1.0 sec.) values in pulmonary function tests. The causes of the occupational allergic reaction in this factory are guessed as follows: 1) control of powdered materials was incomplete in the process of production, 2) various kinds of sensitizing drugs were handled by the same workers.", "contents": "[Some experiments on the allergic reaction among workers in a pharmaceutical factory (author's transl)]. A survey was made on workers handling powdered drugs in a pharmaceutical factory. In this factory, two kinds of anti-inflammatory enzyme (bromelain and trypsin), one anti-inflammatory agent (flufenamic acid), one antispasmodic (flopropion) and two kinds of antibiotics (ampicillin and cephalexin) are mainly produced. Twenty four workers were examined by interviews and checked by Cornell Medical Index, and 18 of them complained of respiratory symptoms. These 18 workers were physically examined by skin scratch tests, pulmonary function tests and serum immunological tests. Among 24 workers, 9 handled powdered drugs (A group), 5 handled the same in the past and had already been transferred to other sections for their symptoms (B group), 3 engaged in the process of capsul-filling (C group) and 7 handled several times occasionally during one year (D group). Their average months spent in handling powdered drugs were, in the case of anti-inflammatory enzyme, A group 53.2, B group 66.2, and in the case of antibiotics, 5 workers in A group 24.0, 2 workers in B group 7.0, 3 workers in C group 25.7. Twenty workers complained of symptoms which were mainly irritation of mucosa including the respiratory system and itching of the skin while they were working, and accelerated nasal discharge, urticaria and asthma after working. Group A and group B were higher than group D in the rate of respiratory complaints in C.M.I. (p less than 0.001). Fourteen workers pointed out anti-inflammatory enzyme as a cause of main symptoms, 7 workers flufenamic acid, 3 workers flopropion, 4 workers antibiotics. Three workers who had past history of asthma or articular rheumatism had been transferred to other sections. Of 18 workers who were physically examined, 11 workers showed positive reactions to skin scratch tests with handling drugs. On 8 workers of them, some kinds of drugs which were pointed out as drugs causing main symptoms reacted positively. Numbers of workers with increased immunoglobin values were, IgE 3, IgM 2, IgA 4, IgM 2. Two workers showed decreased FVC and FEV (1.0 sec.) values in pulmonary function tests. The causes of the occupational allergic reaction in this factory are guessed as follows: 1) control of powdered materials was incomplete in the process of production, 2) various kinds of sensitizing drugs were handled by the same workers."} {"id": "PMID:160480", "title": "[Peritoneoscopy in infancy and childhood, indications, technique and diagnostic value (author's transl)].", "content": "Indications, technique and diagnostic value of peritoneoscopy in infancy and childhood are reviewed from the literature; own results are discussed as well. Peritoneoscopy is an important procedure in the diagnosis of chronic inflammatory liver disease and gonadal dysgenesis in this age group. If other diseases are suspected, non-invasive examination techniques may give sufficient diagnostic information.", "contents": "[Peritoneoscopy in infancy and childhood, indications, technique and diagnostic value (author's transl)]. Indications, technique and diagnostic value of peritoneoscopy in infancy and childhood are reviewed from the literature; own results are discussed as well. Peritoneoscopy is an important procedure in the diagnosis of chronic inflammatory liver disease and gonadal dysgenesis in this age group. If other diseases are suspected, non-invasive examination techniques may give sufficient diagnostic information."} {"id": "PMID:160481", "title": "[Alpha 1-antitrypsin deficiency, liver cirrhosis and pulmonary emphysema (author's transl)].", "content": "It is well known that incidence of chronic obstructive lung disease in adult patients with alpha 1-antitrypsin deficiency (ATD) is high. Adult carriers of this genetic trait with cirrhosis of the liver, and also with fibrosis of the liver and hepatoma, have been reported. A causal relationship between ATD and liver lesions has been suspected. In most cases liver disease has been recognized at post morten, - in a few cases, however, intra vitam, when severe symptoms of the liver disease had become apparent. The case of a 59 year-old patient is reported with PIZZ-homozygous ATD, moderate pulmonary emphysema and with marked portal fibrosis and focal transition in cirrhosis of the liver without any sequelae. The clinical course has been rather benign so far.", "contents": "[Alpha 1-antitrypsin deficiency, liver cirrhosis and pulmonary emphysema (author's transl)]. It is well known that incidence of chronic obstructive lung disease in adult patients with alpha 1-antitrypsin deficiency (ATD) is high. Adult carriers of this genetic trait with cirrhosis of the liver, and also with fibrosis of the liver and hepatoma, have been reported. A causal relationship between ATD and liver lesions has been suspected. In most cases liver disease has been recognized at post morten, - in a few cases, however, intra vitam, when severe symptoms of the liver disease had become apparent. The case of a 59 year-old patient is reported with PIZZ-homozygous ATD, moderate pulmonary emphysema and with marked portal fibrosis and focal transition in cirrhosis of the liver without any sequelae. The clinical course has been rather benign so far."} {"id": "PMID:160487", "title": "Effect of endurance training on myocardial myosin adenosine triphosphatase activity of the dog.", "content": "Endurance exercise training has been found to enhance the functional capacity of the myocardium in several animal models. The sub-cellular phenomena accompanying the augmented function are yet to be explained. The present study sought to determine if the myosin ATPase activity of cardiac muscle increased as a result of endurance conditioning. Five beagles trained by running on a motor driven treadmill (T) and five control (NT) animals were studied. Follwoing 10 weeks of training the T group had a significantly (P less than .05) lower heart rate than the NT while performing the same submaximal exercise and the gastrocnemius cytochrome oxidase activity was significantly greater (P less than .005) in the T than in the NT. These two measurements established that the exercised animals were physically trained. Myosin was isolated from the left ventricular myocardium and activated in a medium containing K-EDTA. No significant (P less than .05) difference in maximum myosin ATPase activity was observed between the NT and T groups in cardiac muscle. It was concluded that cardiac muscle myosin ATPase activity was not affected by 10 weeks of endurance conditioning induced by treadmill running in dogs.", "contents": "Effect of endurance training on myocardial myosin adenosine triphosphatase activity of the dog. Endurance exercise training has been found to enhance the functional capacity of the myocardium in several animal models. The sub-cellular phenomena accompanying the augmented function are yet to be explained. The present study sought to determine if the myosin ATPase activity of cardiac muscle increased as a result of endurance conditioning. Five beagles trained by running on a motor driven treadmill (T) and five control (NT) animals were studied. Follwoing 10 weeks of training the T group had a significantly (P less than .05) lower heart rate than the NT while performing the same submaximal exercise and the gastrocnemius cytochrome oxidase activity was significantly greater (P less than .005) in the T than in the NT. These two measurements established that the exercised animals were physically trained. Myosin was isolated from the left ventricular myocardium and activated in a medium containing K-EDTA. No significant (P less than .05) difference in maximum myosin ATPase activity was observed between the NT and T groups in cardiac muscle. It was concluded that cardiac muscle myosin ATPase activity was not affected by 10 weeks of endurance conditioning induced by treadmill running in dogs."} {"id": "PMID:160489", "title": "Loss of rac locus DNA in merozygotes of Escherichia coli K12.", "content": "DNA-DNA hybridization was used to demonstrate that the substituted DNA in the bacteriophage lambda recE (formerly called lambda reverse) is homologous to DNA at the rac locus in Escherichia coli. Strains that are rac- do not contain appreciable amounts of this DNA, and it is lost from a rac+ episome (F' 123) after transmission to a rac- recipient. This is consistent with the proposal that the rac locus contains a cryptic prophage (Low, 1973).", "contents": "Loss of rac locus DNA in merozygotes of Escherichia coli K12. DNA-DNA hybridization was used to demonstrate that the substituted DNA in the bacteriophage lambda recE (formerly called lambda reverse) is homologous to DNA at the rac locus in Escherichia coli. Strains that are rac- do not contain appreciable amounts of this DNA, and it is lost from a rac+ episome (F' 123) after transmission to a rac- recipient. This is consistent with the proposal that the rac locus contains a cryptic prophage (Low, 1973)."} {"id": "PMID:160490", "title": "Lambda transducing phages derived from a FinO- R100::lambda cointegrate plasmid: proteins encoded by the R100 replication/incompatibility region and the antibiotic resistance determinant.", "content": "Three lambda transducing phages have been isolated from pEDR20, an R100::lambda cointegrate plasmid in which the lambda insertion inactivated the R100 finO gene. Physical analysis of the three phages showed that the lambda is inserted at kilobase coordinate 81.3 of R100. All three phages carry different amounts of R100 DNA in the left arm of lambda. Each pahge contains ISlb, the mer genes and the region between coordinate 81.3 and 88.6; thus, all contain the genes necessary for R100 replication. One phage, VA lambda 73, contains the entire r-determination of R100 in addition to the above DNA. Five proteins coded by the region between 81.3 and 88.6 were detected. These had subunit molecular weights of 10,400; 12,200; 16,200; 19,600; and 38,300. The first was made constitutively and the other four only from a lambda promoter. Other constitutive proteins were one from the cml fus region with a molecular weight of 22,400 (cml) and two from the str sul region with molecular weights of 31,500 (str?) and 30,100 (sul?). Mercuric ion induced synthesis of at least 10 proteins. Six of these were known from earlier work. The total size of the proteins which appear to derive from the mer genes exceeds by a factor of 1.5, the coding capacity of this region without overlapping genes. Some, or all of these extra proteins may be chromosomal in origin, possibly derepressed in response to mercury gene products.", "contents": "Lambda transducing phages derived from a FinO- R100::lambda cointegrate plasmid: proteins encoded by the R100 replication/incompatibility region and the antibiotic resistance determinant. Three lambda transducing phages have been isolated from pEDR20, an R100::lambda cointegrate plasmid in which the lambda insertion inactivated the R100 finO gene. Physical analysis of the three phages showed that the lambda is inserted at kilobase coordinate 81.3 of R100. All three phages carry different amounts of R100 DNA in the left arm of lambda. Each pahge contains ISlb, the mer genes and the region between coordinate 81.3 and 88.6; thus, all contain the genes necessary for R100 replication. One phage, VA lambda 73, contains the entire r-determination of R100 in addition to the above DNA. Five proteins coded by the region between 81.3 and 88.6 were detected. These had subunit molecular weights of 10,400; 12,200; 16,200; 19,600; and 38,300. The first was made constitutively and the other four only from a lambda promoter. Other constitutive proteins were one from the cml fus region with a molecular weight of 22,400 (cml) and two from the str sul region with molecular weights of 31,500 (str?) and 30,100 (sul?). Mercuric ion induced synthesis of at least 10 proteins. Six of these were known from earlier work. The total size of the proteins which appear to derive from the mer genes exceeds by a factor of 1.5, the coding capacity of this region without overlapping genes. Some, or all of these extra proteins may be chromosomal in origin, possibly derepressed in response to mercury gene products."} {"id": "PMID:160491", "title": "Cloning the trpR gene.", "content": "In Escherichia coli, the structural gene for purine nucleoside phosphorylase, deoD, is subject to insertional inactivation by prophage lambda. From one such secondary site lambda lysogen, strain SP265, one may isolate deletions that remove all or part of the trpR gene and other genes in the deo-thr sector of the E. coli chromosome. Specialized transducing phages harboring serB+ and trpR+ were liberated following induction of SP265. All such phages were N-defective, bio-type pseudolysogens whose DNA persisted in the form of plasmids. A collection of transducing phages, differing in their complement of bacterial DNA, was used to locate cleavage sites for BamHI, SalI, and PvuI within the deoD-trpR region of the E. coli genome. The trpR gene lies within a specific 950 base pair BamHI-PvuI segment. A 1250 base pair BamHI fragment carrying a functional trpR gene was cloned into the amplifiable plasmid pBR322. A single SalI site in this fragment was shown to lie within the TrpR gene. In two situations where increased gene dosage might generate elevated amounts of Trp repressor (N-defective trpR+ pseudolysogens and strains harboring pBR322 trpR+ plasmids) neither tryptophan auxotrophy, enhanced sensitivity to DL-5-methyl-tryptophan, nor super repression of the tryptophan biosynthetic enzymes was observed.", "contents": "Cloning the trpR gene. In Escherichia coli, the structural gene for purine nucleoside phosphorylase, deoD, is subject to insertional inactivation by prophage lambda. From one such secondary site lambda lysogen, strain SP265, one may isolate deletions that remove all or part of the trpR gene and other genes in the deo-thr sector of the E. coli chromosome. Specialized transducing phages harboring serB+ and trpR+ were liberated following induction of SP265. All such phages were N-defective, bio-type pseudolysogens whose DNA persisted in the form of plasmids. A collection of transducing phages, differing in their complement of bacterial DNA, was used to locate cleavage sites for BamHI, SalI, and PvuI within the deoD-trpR region of the E. coli genome. The trpR gene lies within a specific 950 base pair BamHI-PvuI segment. A 1250 base pair BamHI fragment carrying a functional trpR gene was cloned into the amplifiable plasmid pBR322. A single SalI site in this fragment was shown to lie within the TrpR gene. In two situations where increased gene dosage might generate elevated amounts of Trp repressor (N-defective trpR+ pseudolysogens and strains harboring pBR322 trpR+ plasmids) neither tryptophan auxotrophy, enhanced sensitivity to DL-5-methyl-tryptophan, nor super repression of the tryptophan biosynthetic enzymes was observed."} {"id": "PMID:160492", "title": "Transcription and membrane attachment of bacteriophage lambda DNA in the absence of N function in the E. coli suA 1 mutant.", "content": "In the polarity suppressor strain psuA 1, we observe a partial N independence of both transcription and DNA-membrane attachment for a lambda NN mutant. These results, in agreement with the genetical data reported by Dambly et al. (1976), suggest that the N product and rho factor are involved in the same process but may not interact directly.", "contents": "Transcription and membrane attachment of bacteriophage lambda DNA in the absence of N function in the E. coli suA 1 mutant. In the polarity suppressor strain psuA 1, we observe a partial N independence of both transcription and DNA-membrane attachment for a lambda NN mutant. These results, in agreement with the genetical data reported by Dambly et al. (1976), suggest that the N product and rho factor are involved in the same process but may not interact directly."} {"id": "PMID:160496", "title": "[Endomyocardiopathy and eosinophilia (author's transl)].", "content": "Clinical, laboratory, and necropsy findings in a male patient with marked eosinophilia and fatal cardiac failure are reported. Necropsy revealed an obliteration of the left ventricle caused by endomyocardial fibrosis, left ventricle hypertrophy, and white thrombus. There was also found endomyocardial fibrosis and hypertrophy of the right ventricle. Pathogenesis and treatment of endomyocardiopathies are discussed.", "contents": "[Endomyocardiopathy and eosinophilia (author's transl)]. Clinical, laboratory, and necropsy findings in a male patient with marked eosinophilia and fatal cardiac failure are reported. Necropsy revealed an obliteration of the left ventricle caused by endomyocardial fibrosis, left ventricle hypertrophy, and white thrombus. There was also found endomyocardial fibrosis and hypertrophy of the right ventricle. Pathogenesis and treatment of endomyocardiopathies are discussed."} {"id": "PMID:160505", "title": "The implantable infusion pump: a new concept in drug delivery.", "content": "Several of our most useful drugs cannot be administered orally. This paper is a summary of our work with a new drug delivery system: a totally implantable, continuous infusion pump, with a self-contained inexhaustible power source. Currently, after bench tests and animal experimentation, we have initiated clinical series utilizing this device to treat individuals with refractory thromboembolic conditions by intravenous heparin, and patients with localized solid tumors by intra-arterial chemotherapy. The use of this device for the infusion of insulin in the management of diabetes mellitus is yet in the laboratory stage of development. In addition to improving dy-today diabetic control and obviating the need for daily insulin injections, this pump offers an ideal opportunity to test whether optimal blood glucose control can significantly prevent or delay the onset of the crippling vascular complications of diabetes. The potential uses of this device, in many fields, are myriad.", "contents": "The implantable infusion pump: a new concept in drug delivery. Several of our most useful drugs cannot be administered orally. This paper is a summary of our work with a new drug delivery system: a totally implantable, continuous infusion pump, with a self-contained inexhaustible power source. Currently, after bench tests and animal experimentation, we have initiated clinical series utilizing this device to treat individuals with refractory thromboembolic conditions by intravenous heparin, and patients with localized solid tumors by intra-arterial chemotherapy. The use of this device for the infusion of insulin in the management of diabetes mellitus is yet in the laboratory stage of development. In addition to improving dy-today diabetic control and obviating the need for daily insulin injections, this pump offers an ideal opportunity to test whether optimal blood glucose control can significantly prevent or delay the onset of the crippling vascular complications of diabetes. The potential uses of this device, in many fields, are myriad."} {"id": "PMID:160508", "title": "Partial characterization of a phosphoryl group transferring enzyme in the membrane of catecholamine storage vesicles.", "content": "Phosphoryl group transfer from ATP to ADP occurred in the isolated membrane of catecholamine storage vesicles. The reaction was accelerated by extraction of the membranes with 50% (v/v) acetone and by treatment with 1% (v/v) Triton X-100. The phosphoryl group transfer reaction was activated by Mg2+ and by Mn2+. The activation profile differed from that obtained for the ATPase activity. The Michaelis-Menten kinetics of the phosphoryl transfer reaction were not entirely linear. From the linear parts of the double reciprocal plots KmATP approximately equal to 1 mM and KmADP approximately equal to 0.4 mM was obtained. All lines of the double reciprocal plots intersected indicating a sequential reaction mechanism. The reaction exhibited a narrow specificity for nucleoside diphospate and a broader one for nucleoside triphosphate indicating that ADP was the true substrate. The transfer reaction was slightly inhibited by AMP, orthophosphate and P1, P5-di(adenosine-5')pentaphosphate. The thiol reagents, N-ethylmaleimide and para-chloromercuribenzoate (PCMB), affected the ATPase activity and the phosphoryl transfer activity differently: with the blockade of 2.4 essential thiol equivalents by N-ethylmaleimide the ATPase was inhibited 50% and net uptake of catecholamine ceased, while the phosphoryl transfer remained unimpaired. PCMB affected both, the ATPase activity and phosphoryl transfer reaction. Treatment of the membranes with dithioerythritol prevented the PCMB-induced inhibition of the phosphoryl transfer, but was ineffective in protecting the ATPase activity, indicating that different thiol groups must be involved in the both enzymatic activities.", "contents": "Partial characterization of a phosphoryl group transferring enzyme in the membrane of catecholamine storage vesicles. Phosphoryl group transfer from ATP to ADP occurred in the isolated membrane of catecholamine storage vesicles. The reaction was accelerated by extraction of the membranes with 50% (v/v) acetone and by treatment with 1% (v/v) Triton X-100. The phosphoryl group transfer reaction was activated by Mg2+ and by Mn2+. The activation profile differed from that obtained for the ATPase activity. The Michaelis-Menten kinetics of the phosphoryl transfer reaction were not entirely linear. From the linear parts of the double reciprocal plots KmATP approximately equal to 1 mM and KmADP approximately equal to 0.4 mM was obtained. All lines of the double reciprocal plots intersected indicating a sequential reaction mechanism. The reaction exhibited a narrow specificity for nucleoside diphospate and a broader one for nucleoside triphosphate indicating that ADP was the true substrate. The transfer reaction was slightly inhibited by AMP, orthophosphate and P1, P5-di(adenosine-5')pentaphosphate. The thiol reagents, N-ethylmaleimide and para-chloromercuribenzoate (PCMB), affected the ATPase activity and the phosphoryl transfer activity differently: with the blockade of 2.4 essential thiol equivalents by N-ethylmaleimide the ATPase was inhibited 50% and net uptake of catecholamine ceased, while the phosphoryl transfer remained unimpaired. PCMB affected both, the ATPase activity and phosphoryl transfer reaction. Treatment of the membranes with dithioerythritol prevented the PCMB-induced inhibition of the phosphoryl transfer, but was ineffective in protecting the ATPase activity, indicating that different thiol groups must be involved in the both enzymatic activities."} {"id": "PMID:160509", "title": "Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit.", "content": "In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS.", "contents": "Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit. In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS."} {"id": "PMID:160510", "title": "Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor lymph node cells from mice bearing methylcholanthrene-induced sarcomas.", "content": "Suppression of cell-mediated cytotoxicity directed against tumor-associated membrane antigens of methylcholanthrene (MC)-induced sarcomas by lymph node cells (LNC) from tumor-bearing mice was examined by inhibition of the 3H-thymidine incorporation assay. Normal LNC from B10 mice had been sensitized in vitro by 6-day cultivation on layers of irradiated syngeneic sarcoma cells and the effect of the generated cytotoxic lymphocytes was then inhibited by the admixture of suppressor cells present in lymph nodes of tumor-bearing mice. Suppressor cells were detected in lymph nodes from 7 of 16 (44 per cent) individually examined tumor bearers when LNC were added to cytotoxic lymphocytes which had been presensitized in vitro. When the experimental schedule was reverted and the tumor bearers' LNC were admixed to the normal LNC prior to the in vitro sensitization so that they were present in the population of the effector cells throughout the period of sensitization, the suppressor effect was detected in only 1 of 9 (11 per cent) tumor-bearers. The suppressive effect of tumor bearers' LNC was found to be nonspecific, being elicited not only by LNC derived from bearers of the sensitizing tumor, but also by LNC from bearers of an unrelated, immunologically noncross-reacting MC-induced sarcoma.", "contents": "Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor lymph node cells from mice bearing methylcholanthrene-induced sarcomas. Suppression of cell-mediated cytotoxicity directed against tumor-associated membrane antigens of methylcholanthrene (MC)-induced sarcomas by lymph node cells (LNC) from tumor-bearing mice was examined by inhibition of the 3H-thymidine incorporation assay. Normal LNC from B10 mice had been sensitized in vitro by 6-day cultivation on layers of irradiated syngeneic sarcoma cells and the effect of the generated cytotoxic lymphocytes was then inhibited by the admixture of suppressor cells present in lymph nodes of tumor-bearing mice. Suppressor cells were detected in lymph nodes from 7 of 16 (44 per cent) individually examined tumor bearers when LNC were added to cytotoxic lymphocytes which had been presensitized in vitro. When the experimental schedule was reverted and the tumor bearers' LNC were admixed to the normal LNC prior to the in vitro sensitization so that they were present in the population of the effector cells throughout the period of sensitization, the suppressor effect was detected in only 1 of 9 (11 per cent) tumor-bearers. The suppressive effect of tumor bearers' LNC was found to be nonspecific, being elicited not only by LNC derived from bearers of the sensitizing tumor, but also by LNC from bearers of an unrelated, immunologically noncross-reacting MC-induced sarcoma."} {"id": "PMID:160511", "title": "Extrusion of peritoneal catheter through abdominal incision: report of a rare complication of ventriculoperitoneal shunt.", "content": "A rare complication of a ventriculoperitoneal shunt is reported. The peritoneal catheter extruded through the well-healed abdominal incision. This is the first report of such an occurrence in an adult patient.", "contents": "Extrusion of peritoneal catheter through abdominal incision: report of a rare complication of ventriculoperitoneal shunt. A rare complication of a ventriculoperitoneal shunt is reported. The peritoneal catheter extruded through the well-healed abdominal incision. This is the first report of such an occurrence in an adult patient."} {"id": "PMID:160513", "title": "Evaluation of electrode array material for neural prostheses.", "content": "Matrix support materials for brain surface electrodes used in neuroprosthetic applications were evaluated after chronic subdural implantation over the parietal cortex of the cat. Four types of array fabricated with Silastic, Dacron mesh, or platinum wire annuli were implanted for periods ranging from 5 weeks to 1 year. We evaluated the arrays by access resistance measurements and gross and histological observations of the tissue beneath both nonstimulated and stimulated electrodes. A porous type matrix constructed of Dacron mesh proved to be the superior design because of its minimal compression of the cortical surface, facility of handling during implantation and autopsy, and satisfactory electrical characteristics provided by a good electrode-brain interface. (Neurosurgery, 5: 681--686, 1979).", "contents": "Evaluation of electrode array material for neural prostheses. Matrix support materials for brain surface electrodes used in neuroprosthetic applications were evaluated after chronic subdural implantation over the parietal cortex of the cat. Four types of array fabricated with Silastic, Dacron mesh, or platinum wire annuli were implanted for periods ranging from 5 weeks to 1 year. We evaluated the arrays by access resistance measurements and gross and histological observations of the tissue beneath both nonstimulated and stimulated electrodes. A porous type matrix constructed of Dacron mesh proved to be the superior design because of its minimal compression of the cortical surface, facility of handling during implantation and autopsy, and satisfactory electrical characteristics provided by a good electrode-brain interface. (Neurosurgery, 5: 681--686, 1979)."} {"id": "PMID:160516", "title": "Oesophageal ulceration due to slow-release potassium in the presence of left atrial enlargement.", "content": "Ulceration of the oesophagus was suspected clinically and confirmed radiologically in a patient with an enlarged left atrium while on treatment with slow release potassium chloride. Its discontinuation resulted in resolution of symptoms. This potentially serious complication of treatment should be considered in patients with enlargement of the left atrium who develop dysphagia. It is avoided by using soluble forms of potassium chloride replacement.", "contents": "Oesophageal ulceration due to slow-release potassium in the presence of left atrial enlargement. Ulceration of the oesophagus was suspected clinically and confirmed radiologically in a patient with an enlarged left atrium while on treatment with slow release potassium chloride. Its discontinuation resulted in resolution of symptoms. This potentially serious complication of treatment should be considered in patients with enlargement of the left atrium who develop dysphagia. It is avoided by using soluble forms of potassium chloride replacement."} {"id": "PMID:160518", "title": "Ocular findings in cytogenetic syndromes.", "content": "Several cytogenetic syndromes are reviewed, and the salient ocular and facial abnormalities that might lead to a diagnosis are pointed out. Examples are given of mongoloid slant to the palpebral fissures, not only in Down's syndrome, but also in monosomy 9p, where, in addition, the triangular skull is almost diagnostic. Antimongoloid slant is found in trisomy 9p, where the eyes also have enophthalmos of monosomy 9p. Hypertelorism is another common finding in these syndromes; in monosomy 5p it is almost always present, although it occurs in other conditions as well, including trisomy 12p. The ring 22 syndrome has a distinguishing finding called \"doe's eyes\" because of the shape of the palpebral fissures. Trisomy 13 has numerous ocular findings as well as skull and facial involvements.", "contents": "Ocular findings in cytogenetic syndromes. Several cytogenetic syndromes are reviewed, and the salient ocular and facial abnormalities that might lead to a diagnosis are pointed out. Examples are given of mongoloid slant to the palpebral fissures, not only in Down's syndrome, but also in monosomy 9p, where, in addition, the triangular skull is almost diagnostic. Antimongoloid slant is found in trisomy 9p, where the eyes also have enophthalmos of monosomy 9p. Hypertelorism is another common finding in these syndromes; in monosomy 5p it is almost always present, although it occurs in other conditions as well, including trisomy 12p. The ring 22 syndrome has a distinguishing finding called \"doe's eyes\" because of the shape of the palpebral fissures. Trisomy 13 has numerous ocular findings as well as skull and facial involvements."} {"id": "PMID:160521", "title": "Psychological disturbance and pain report differences in both organic and non-organic low back pain patients.", "content": "Patients with undiagnosable low back pain have been observed to differ from patients with proven low back pain in their clinical description of pain and in their psychological status. More variable and diffuse pain qualities are emphasized in their clinical reports and more psychological disturbance characterizes them as a group, suggesting an association between pain expression and psychological disturbance. One hundred and two patients with low back pain were administered a standardized pain questionnaire to determine more systematically the association between pain expression and psychological disturbance in patients with and without demonstrable organic disease. Patients with psychological disturbance differed significantly from patients without psychological disturbance in the following ways. They used more words in their description of pain, distributed these words over more pain factors, and endorsed significantly more pain of the affective and skin pressure variety. The results underscore previous clinical impressions and suggest that patients without either organic or psychological findings may be cases of undiagnosed organic disease.", "contents": "Psychological disturbance and pain report differences in both organic and non-organic low back pain patients. Patients with undiagnosable low back pain have been observed to differ from patients with proven low back pain in their clinical description of pain and in their psychological status. More variable and diffuse pain qualities are emphasized in their clinical reports and more psychological disturbance characterizes them as a group, suggesting an association between pain expression and psychological disturbance. One hundred and two patients with low back pain were administered a standardized pain questionnaire to determine more systematically the association between pain expression and psychological disturbance in patients with and without demonstrable organic disease. Patients with psychological disturbance differed significantly from patients without psychological disturbance in the following ways. They used more words in their description of pain, distributed these words over more pain factors, and endorsed significantly more pain of the affective and skin pressure variety. The results underscore previous clinical impressions and suggest that patients without either organic or psychological findings may be cases of undiagnosed organic disease."} {"id": "PMID:160522", "title": "Skeletal muscle analysis of wheelchair athletes.", "content": "The present study reports the results of using the biopsy technique with members of the Canadian Wheelchair Internation Team. The results demonstrate that these athletes possess muscles with large fibre areas than seen in Olympic athletes.", "contents": "Skeletal muscle analysis of wheelchair athletes. The present study reports the results of using the biopsy technique with members of the Canadian Wheelchair Internation Team. The results demonstrate that these athletes possess muscles with large fibre areas than seen in Olympic athletes."} {"id": "PMID:160537", "title": "Instantaneous measurement of glomerular filtration rate in the isolated perfused rat kidney.", "content": "In perfusion studies on the isolated cellfree perfused rat kidney, the glomerular filtration rate (GFR) can be controlled if the GFR can be measured instantaneously. This paper reports on a GFR meter which opens this possibility. Vitamin B12 is used as a marker for the GFR. A bubble flow meter determines urine flow rates ranging from 10 up to 200 microliter-min-1. A fiberoptic colorimeter measures vitamin B12 concentrations in the urine up to 400 mg-l-1. The flow meter and the colorimeter are described in detail. The reliability of vitamin B12 as a marker for the GFR is demonstrated and, moreover, the identity of GFR values obtained with the GFR meter and those from B12 spectrophotometry is demonstrated.", "contents": "Instantaneous measurement of glomerular filtration rate in the isolated perfused rat kidney. In perfusion studies on the isolated cellfree perfused rat kidney, the glomerular filtration rate (GFR) can be controlled if the GFR can be measured instantaneously. This paper reports on a GFR meter which opens this possibility. Vitamin B12 is used as a marker for the GFR. A bubble flow meter determines urine flow rates ranging from 10 up to 200 microliter-min-1. A fiberoptic colorimeter measures vitamin B12 concentrations in the urine up to 400 mg-l-1. The flow meter and the colorimeter are described in detail. The reliability of vitamin B12 as a marker for the GFR is demonstrated and, moreover, the identity of GFR values obtained with the GFR meter and those from B12 spectrophotometry is demonstrated."} {"id": "PMID:160538", "title": "[Dictyocaulus viviparus in Denmark. A survey of 15 years' diagnostic examination of faeces samples (author's transl)].", "content": "On the basis of routine diagnostic examinations of 12424 bovine faeces samples for larvae of Dictyocaulus viviparus, performed during the period 1963 through 1977, some calculations and reflections have been made on the incidence and epidemiology of lungworm infection in cattle in Denmark. It seems justified to conclude that dictyocaulosis is an important disease in heifers and cows as well as in calves. A distinct seasonal variation in the incidence of lungworm infection is apparent, in that more than 85% of the faeces samples were submitted within the period July through October. Lungworm larvae could be demonstrated in faeces samples from cattle during the winter and spring- This is considered to be of great importance with a view to re-establishment of the infection in the following grazing season. Overwintering of larvae on pastures seems possible. too, since patent infections among calves were demonstrated already in May and June. A comparison of meteorological data with totals of samples submitted and with relative numbers of positive samples seems to confirm, that both the level and the spread of lungworm infections are influenced by the amount of rainfall during the period June through August.", "contents": "[Dictyocaulus viviparus in Denmark. A survey of 15 years' diagnostic examination of faeces samples (author's transl)]. On the basis of routine diagnostic examinations of 12424 bovine faeces samples for larvae of Dictyocaulus viviparus, performed during the period 1963 through 1977, some calculations and reflections have been made on the incidence and epidemiology of lungworm infection in cattle in Denmark. It seems justified to conclude that dictyocaulosis is an important disease in heifers and cows as well as in calves. A distinct seasonal variation in the incidence of lungworm infection is apparent, in that more than 85% of the faeces samples were submitted within the period July through October. Lungworm larvae could be demonstrated in faeces samples from cattle during the winter and spring- This is considered to be of great importance with a view to re-establishment of the infection in the following grazing season. Overwintering of larvae on pastures seems possible. too, since patent infections among calves were demonstrated already in May and June. A comparison of meteorological data with totals of samples submitted and with relative numbers of positive samples seems to confirm, that both the level and the spread of lungworm infections are influenced by the amount of rainfall during the period June through August."} {"id": "PMID:160542", "title": "[The repair of inguinal hernia by insertion of prosthetic material with tunnelisation of the spermatic cord (author's transl)].", "content": "A mersilene plate, cut according to the technique of Zagdoun, usually fixed to the conjoint tendon (in front of the latter) and to the inguinal ligament, is turned in front of the spermatic cord in the form of a cuff attached to itself and the aponeurosis of the obliquus externus. Thus strengthens the deficient deep and superfical anatomical layers in cases of large or recurrent inguinal hernia.", "contents": "[The repair of inguinal hernia by insertion of prosthetic material with tunnelisation of the spermatic cord (author's transl)]. A mersilene plate, cut according to the technique of Zagdoun, usually fixed to the conjoint tendon (in front of the latter) and to the inguinal ligament, is turned in front of the spermatic cord in the form of a cuff attached to itself and the aponeurosis of the obliquus externus. Thus strengthens the deficient deep and superfical anatomical layers in cases of large or recurrent inguinal hernia."} {"id": "PMID:160543", "title": "[Controlled therapeutic \"evisceration\" in so-called \"terminal\" peritonitis (author's transl)].", "content": "Absence of closure of the abdominal wound following reoperation for severe peritonitis is an additional therapeutic technique in dealing with peritoneal infection. However, this technique poses the problem of covering the loops of the small intestine in order to avoid fistulisation in the exposed viscera. The loops are initially protected by a \"wound protector\" or covered with a plate of polyurethane foam. Secondarily, when the peritoneal cavity is clean, the open wound is converted to an incisional hernia by a thin dermo-epidermal graft in strips, applied to the granulation tissue. This technique is effective and would seem to be simpler than detachments, plasties and relieving incisions.", "contents": "[Controlled therapeutic \"evisceration\" in so-called \"terminal\" peritonitis (author's transl)]. Absence of closure of the abdominal wound following reoperation for severe peritonitis is an additional therapeutic technique in dealing with peritoneal infection. However, this technique poses the problem of covering the loops of the small intestine in order to avoid fistulisation in the exposed viscera. The loops are initially protected by a \"wound protector\" or covered with a plate of polyurethane foam. Secondarily, when the peritoneal cavity is clean, the open wound is converted to an incisional hernia by a thin dermo-epidermal graft in strips, applied to the granulation tissue. This technique is effective and would seem to be simpler than detachments, plasties and relieving incisions."} {"id": "PMID:160544", "title": "Cleavage of single-stranded DNA by the A and A* proteins of bacteriophage phi X174.", "content": "The purified A protein and A* protein of bacteriophage phi X174 have been tested for endonuclease activity on single stranded viral phi X174 DNA. The A protein (55.000 daltons) nicks single-stranded DNA in the same way and at the same place as it does superhelical RFI DNA, at the origin of DNA replication. The A* protein (37.000 daltons) can cleave the single-stranded viral DNA at many different sites. It has however a strong preference for the origin of replication. Both proteins generate 3'OH ends and blocked 5' termini at the nick site.", "contents": "Cleavage of single-stranded DNA by the A and A* proteins of bacteriophage phi X174. The purified A protein and A* protein of bacteriophage phi X174 have been tested for endonuclease activity on single stranded viral phi X174 DNA. The A protein (55.000 daltons) nicks single-stranded DNA in the same way and at the same place as it does superhelical RFI DNA, at the origin of DNA replication. The A* protein (37.000 daltons) can cleave the single-stranded viral DNA at many different sites. It has however a strong preference for the origin of replication. Both proteins generate 3'OH ends and blocked 5' termini at the nick site."} {"id": "PMID:160545", "title": "Studies on the binding of lambda Int protein to attachment site DNA: identification of a tight-binding site in the P' region.", "content": "We have used three approaches to studying the interaction of lambda Int protein with bacteriophage attachment site DNA, POP': location of binding sites by retention of DNA fragments in a filter binding assay, reconstruction of a binding site by DNA synthesis and protection of a binding site from an exonuclease. Retention of restriction fragments on nitrocellulose filters in the presence of Int protein was used to locate binding sites. A high affinity binding site lies in P' between base pairs -6 and +173 from the center of the common core sequence, and low affinity sites are found in the 200 base pair region left of position -6. Reconstruction of the high affinity binding site region from the right using primed DNA synthesis and testing for filter binding in the presence of Int protein shows that sequences sufficient for tight binding of Int protein lie to the right of position +66. When attachment site DNA is protected by bound Int protein against digestion by exonuclease III, four Int dependent protection bands are seen in positions +58, +68, +79 and +88. This can be interpreted either as showing that four Int protein monomers bind to the high affinity region in series, or as evidence for wrapping of the DNA around Int protein, leading to structural changes resembling those occurring to DNA in nucleosomes.", "contents": "Studies on the binding of lambda Int protein to attachment site DNA: identification of a tight-binding site in the P' region. We have used three approaches to studying the interaction of lambda Int protein with bacteriophage attachment site DNA, POP': location of binding sites by retention of DNA fragments in a filter binding assay, reconstruction of a binding site by DNA synthesis and protection of a binding site from an exonuclease. Retention of restriction fragments on nitrocellulose filters in the presence of Int protein was used to locate binding sites. A high affinity binding site lies in P' between base pairs -6 and +173 from the center of the common core sequence, and low affinity sites are found in the 200 base pair region left of position -6. Reconstruction of the high affinity binding site region from the right using primed DNA synthesis and testing for filter binding in the presence of Int protein shows that sequences sufficient for tight binding of Int protein lie to the right of position +66. When attachment site DNA is protected by bound Int protein against digestion by exonuclease III, four Int dependent protection bands are seen in positions +58, +68, +79 and +88. This can be interpreted either as showing that four Int protein monomers bind to the high affinity region in series, or as evidence for wrapping of the DNA around Int protein, leading to structural changes resembling those occurring to DNA in nucleosomes."} {"id": "PMID:160546", "title": "Size fractionation of DNA fragments by liquid-liquid chromatography.", "content": "A method for the fractionation of double-stranded DNA fragments from 150 to 22000 b.p. in size by liquid-liquid chromatography is described. The procedure makes use of the fact that the partitioning of DNA in a polyethylene glycol-dextran system is size dependent and can be altered by alkali metal cations. Cellulose or celite are used as supports for the stationary, dextran-rich phase. Examples show the fractionation of digests of T7 DNA produced by Dpn II and Hind II restriction endonulceases as well as lambda DNA digests produced by Hind III and Eco RI restriction endonucleases.", "contents": "Size fractionation of DNA fragments by liquid-liquid chromatography. A method for the fractionation of double-stranded DNA fragments from 150 to 22000 b.p. in size by liquid-liquid chromatography is described. The procedure makes use of the fact that the partitioning of DNA in a polyethylene glycol-dextran system is size dependent and can be altered by alkali metal cations. Cellulose or celite are used as supports for the stationary, dextran-rich phase. Examples show the fractionation of digests of T7 DNA produced by Dpn II and Hind II restriction endonulceases as well as lambda DNA digests produced by Hind III and Eco RI restriction endonucleases."} {"id": "PMID:160548", "title": "Possible role of the serotonergic system in the behavioral effect of massed electroconvulsive shock in rat.", "content": "Massed electroconvulsive shock (ECS) inhibited escape in a one-way avoidance system and tolerance to this effect developed in rats shocked for 4 consecutive days (1, 4, 5 and 10 ECS respectively). Chronic treatment with p-bromo-N-methylamphetamine (V-III) as well as pretreatment with pCPA antagonized the behavioral disturbing effect of massed ECS strongly supporting the idea that 5-HT plays an important role in observed behavioral effects.", "contents": "Possible role of the serotonergic system in the behavioral effect of massed electroconvulsive shock in rat. Massed electroconvulsive shock (ECS) inhibited escape in a one-way avoidance system and tolerance to this effect developed in rats shocked for 4 consecutive days (1, 4, 5 and 10 ECS respectively). Chronic treatment with p-bromo-N-methylamphetamine (V-III) as well as pretreatment with pCPA antagonized the behavioral disturbing effect of massed ECS strongly supporting the idea that 5-HT plays an important role in observed behavioral effects."} {"id": "PMID:160554", "title": "Molecular cloning of human epsilon-globin gene.", "content": "Human beta-like globin genes were investigated by use of rabbit beta-globin cDNA plasmid as a cross-species hybridization probe. Normal and beta 0/delta beta 0 thalassemic DNA were compared by filter hybridization procedures. It proved possible to demonstrate that the rabbit probe detected G gamma, A gamma, delta, beta, beta 0, and delta beta 0 human globin genes as well as an additional unidentified beta-like globin gene. By use of an agarose gel elution procedure, fractions of HindIII-digested DNA enriched for beta-like globin genes were purified. One of these fractions, 8.0 kilobases in size, was clonedinto lambda 788, and EK2 lambda HindIII vector. A positive clone was obtained and characterized by restriction mapping and sequence analysis. The sequence data obtained predicted an amino acid sequence that exactly matches a part of human epsilon-globin. The human non-alpha-globin locus is now nearly complete. delta, beta, and gamma human globin genes have already been cloned and analyzed. We describe here the cloning of the remaining non-alpha-globin gene, epsilon.", "contents": "Molecular cloning of human epsilon-globin gene. Human beta-like globin genes were investigated by use of rabbit beta-globin cDNA plasmid as a cross-species hybridization probe. Normal and beta 0/delta beta 0 thalassemic DNA were compared by filter hybridization procedures. It proved possible to demonstrate that the rabbit probe detected G gamma, A gamma, delta, beta, beta 0, and delta beta 0 human globin genes as well as an additional unidentified beta-like globin gene. By use of an agarose gel elution procedure, fractions of HindIII-digested DNA enriched for beta-like globin genes were purified. One of these fractions, 8.0 kilobases in size, was clonedinto lambda 788, and EK2 lambda HindIII vector. A positive clone was obtained and characterized by restriction mapping and sequence analysis. The sequence data obtained predicted an amino acid sequence that exactly matches a part of human epsilon-globin. The human non-alpha-globin locus is now nearly complete. delta, beta, and gamma human globin genes have already been cloned and analyzed. We describe here the cloning of the remaining non-alpha-globin gene, epsilon."} {"id": "PMID:160555", "title": "Dynein binds to and crossbridges cytoplasmic microtubules.", "content": "Dynein isolated from Chlamydomonas flagellar axonemes binds to microtubules assembled in vitro from 6S brain tubulin dimers. The dynein arms bind periodically along the length of the microtubules with a center-to-center spacing of 24 nm, equal to the periodicity of dynein arms on intact axonemes. The arms project from the in vitro assembled microtubules at an angle of approximately 55 degrees, thereby defining microtubule polarity. Dynein cosediments with microtubules through a sucrose gradient, as demonstrated by electron microscopy, gel electrophoresis, and ATPase analysis. In addition, dynein induces crossbridging between adjacent microtubules. Darkfield microscopy reveals that microtubules containing dynein are aggregated into large bundles; electron microscopy indicates that microtubules of the same polarity are crossbridged by a regular array of arms. Viewed by darkfield microscopy, addition of ATP to crossbridged microtubules causes their disaggregation; electron microscopy shows that the majority of these microtubules are no longer crossbridged. These observations are applicable to the determination of microtubule polarity and directionality of microtubule assembly in situ and suggest a role for dynein in cytoplasmic microtubule-based cellular movements.", "contents": "Dynein binds to and crossbridges cytoplasmic microtubules. Dynein isolated from Chlamydomonas flagellar axonemes binds to microtubules assembled in vitro from 6S brain tubulin dimers. The dynein arms bind periodically along the length of the microtubules with a center-to-center spacing of 24 nm, equal to the periodicity of dynein arms on intact axonemes. The arms project from the in vitro assembled microtubules at an angle of approximately 55 degrees, thereby defining microtubule polarity. Dynein cosediments with microtubules through a sucrose gradient, as demonstrated by electron microscopy, gel electrophoresis, and ATPase analysis. In addition, dynein induces crossbridging between adjacent microtubules. Darkfield microscopy reveals that microtubules containing dynein are aggregated into large bundles; electron microscopy indicates that microtubules of the same polarity are crossbridged by a regular array of arms. Viewed by darkfield microscopy, addition of ATP to crossbridged microtubules causes their disaggregation; electron microscopy shows that the majority of these microtubules are no longer crossbridged. These observations are applicable to the determination of microtubule polarity and directionality of microtubule assembly in situ and suggest a role for dynein in cytoplasmic microtubule-based cellular movements."} {"id": "PMID:160556", "title": "Increased expression of a eukaryotic gene in Escherichia coli through stabilization of its messenger RNA.", "content": "The expression of a cloned eukaryotic gene [catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) (qa-2+) from Neurospora crassa] is dramatically increased (as much as 100-fold) in Escherichia coli strains deficient in polynucleotide phosphorylase (pnp) (polynucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8) and RNase I (rna). The increased expression is controlled primarily by the absence of polynucleotide phosphorylase and appears to be specific for the eukaryotic gene. No increase in the specific activity of either chromosomal or plasmid-borne prokaryotic genes has been observed. In polynucleotide phosphorylase-deficient strains of E. coli the half-life of plasmid (pVK88, ampr qa-2+)-encoded mRNAs increases from 1.0 to 2.8 min. This increase must be due primarily to stabilization of the aq-2 mRNA because no increase in the half-lives of pBR322 vehicle mRNAs was observed in polynucleotide phosphorylase-deficient strains. These results suggest that there are inherent structural differences between prokaryotic and eukaryotic mRNAs.", "contents": "Increased expression of a eukaryotic gene in Escherichia coli through stabilization of its messenger RNA. The expression of a cloned eukaryotic gene [catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) (qa-2+) from Neurospora crassa] is dramatically increased (as much as 100-fold) in Escherichia coli strains deficient in polynucleotide phosphorylase (pnp) (polynucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8) and RNase I (rna). The increased expression is controlled primarily by the absence of polynucleotide phosphorylase and appears to be specific for the eukaryotic gene. No increase in the specific activity of either chromosomal or plasmid-borne prokaryotic genes has been observed. In polynucleotide phosphorylase-deficient strains of E. coli the half-life of plasmid (pVK88, ampr qa-2+)-encoded mRNAs increases from 1.0 to 2.8 min. This increase must be due primarily to stabilization of the aq-2 mRNA because no increase in the half-lives of pBR322 vehicle mRNAs was observed in polynucleotide phosphorylase-deficient strains. These results suggest that there are inherent structural differences between prokaryotic and eukaryotic mRNAs."} {"id": "PMID:160557", "title": "Gene expression of an Escherichia coli ribosomal RNA promoter fused to structural genes of the galactose operon.", "content": "The promoter region of the rrnB ribosomal RNA gene of Escherichia coli has been ligated within the epimerase gene (galE) of the galactose operon in a lambda phage vector. The recombinant lambda phage has been characterized by restriction mapping and assays of both galK (galactokinase) gene activity and galactose messenger RNA hybridization. In such lyosgens, expression of the fused galactose operon occurs as a function of growth rate in a manner characteristic of ribosomal RNA gene expression and is subject to stringent control by amino acid availability for protein synthesis. Galactose messenger RNA arising from the ribosomal promoter is not as metabolically stable as ribosomal RNA.", "contents": "Gene expression of an Escherichia coli ribosomal RNA promoter fused to structural genes of the galactose operon. The promoter region of the rrnB ribosomal RNA gene of Escherichia coli has been ligated within the epimerase gene (galE) of the galactose operon in a lambda phage vector. The recombinant lambda phage has been characterized by restriction mapping and assays of both galK (galactokinase) gene activity and galactose messenger RNA hybridization. In such lyosgens, expression of the fused galactose operon occurs as a function of growth rate in a manner characteristic of ribosomal RNA gene expression and is subject to stringent control by amino acid availability for protein synthesis. Galactose messenger RNA arising from the ribosomal promoter is not as metabolically stable as ribosomal RNA."} {"id": "PMID:160558", "title": "Role of thymidylate synthetase activity in development of methotrexate cytotoxicity.", "content": "Methotrexate (MTX) inhibition of the growth of mouse or human leukemia cells in culture was partially prevented by either thymidine (dThd) or hypoxanthine. 5-Fluoro-2'-deoxyuridine (FdUrd) also decreased the growth-inhibitory potency of MTX in the presence of small concentrations of 5-formyltetrahydrofolate (citrovorum factor) and sufficient exogenous dThd to support the synthesis of thymidylate nucleotides by salvage mechanisms. In addition, citrovorum factor-induced reversal of MTX was several orders of magnitude more efficient in the presence of both FdUrd and dThd than in the presence of dThd alone or in the absence of both nucleosides. Likewise, the presence of FdUrd (3 microM) and dThd (5.6 microM) completely prevented the lethality of 0.3 mM MTX to L1210 cells in culture medium supplemented with micromolar concentrations of citrovorum factor. We propose that this protection against the cytotoxic effects of MTX by dThd, hypoxanthine, and FdUrd have a common biochemical mechanism--namely, inhibition of the de novo synthesis of thymidylate by either a direct [FdUrd; inhibition of thymidylate synthetase (thymidylate synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyl-transferase, EC 2.1.1.45)] or indirect (dThd and hypoxanthine; feedback inhibition by anabolites on ribonucleotide reductase and deoxycytidylate deaminase) effect. The resultant decreased rate of loss of reduced folates due to de novo thymidylate synthesis would allow a higher degree of inhibition of dihydrofolate reductase to be endured without damage to the cell.", "contents": "Role of thymidylate synthetase activity in development of methotrexate cytotoxicity. Methotrexate (MTX) inhibition of the growth of mouse or human leukemia cells in culture was partially prevented by either thymidine (dThd) or hypoxanthine. 5-Fluoro-2'-deoxyuridine (FdUrd) also decreased the growth-inhibitory potency of MTX in the presence of small concentrations of 5-formyltetrahydrofolate (citrovorum factor) and sufficient exogenous dThd to support the synthesis of thymidylate nucleotides by salvage mechanisms. In addition, citrovorum factor-induced reversal of MTX was several orders of magnitude more efficient in the presence of both FdUrd and dThd than in the presence of dThd alone or in the absence of both nucleosides. Likewise, the presence of FdUrd (3 microM) and dThd (5.6 microM) completely prevented the lethality of 0.3 mM MTX to L1210 cells in culture medium supplemented with micromolar concentrations of citrovorum factor. We propose that this protection against the cytotoxic effects of MTX by dThd, hypoxanthine, and FdUrd have a common biochemical mechanism--namely, inhibition of the de novo synthesis of thymidylate by either a direct [FdUrd; inhibition of thymidylate synthetase (thymidylate synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyl-transferase, EC 2.1.1.45)] or indirect (dThd and hypoxanthine; feedback inhibition by anabolites on ribonucleotide reductase and deoxycytidylate deaminase) effect. The resultant decreased rate of loss of reduced folates due to de novo thymidylate synthesis would allow a higher degree of inhibition of dihydrofolate reductase to be endured without damage to the cell."} {"id": "PMID:160559", "title": "Migration of Schwann cells and wrapping of neurites in vitro: a function of protease activity (plasmin) in the growth medium.", "content": "In vitro conditions were defined under which Schwann cells, from a population of dissociated embryonic chicken spinal cord cells, migrate along the growing neuronal fibers and wrap bundles as well as individual axons, in a pattern similar to that found in a developing peripheral nervous system in vivo. The migration of Schwann cells and their wrapping of nerve fibers was found to be a function of plasmin activity in the growth medium. It was determined that at least one cell type among the spinal cord cells is producing plasminogen activator, the enzyme that activates the plasminogen that is a constituent of any serum. It is concluded that, to achieve wrapping of neurons by Schwann cells in culture, it is essential to have an active plasmin-generating system in the medium. It is hypothesized that the Schwann cell produces plasminogen activator. The possible role of both the Schwann cell and the plasminogen possible role of both the Schwann cell and the plasminogen activator in the formation of the neuromuscular junction is discussed.", "contents": "Migration of Schwann cells and wrapping of neurites in vitro: a function of protease activity (plasmin) in the growth medium. In vitro conditions were defined under which Schwann cells, from a population of dissociated embryonic chicken spinal cord cells, migrate along the growing neuronal fibers and wrap bundles as well as individual axons, in a pattern similar to that found in a developing peripheral nervous system in vivo. The migration of Schwann cells and their wrapping of nerve fibers was found to be a function of plasmin activity in the growth medium. It was determined that at least one cell type among the spinal cord cells is producing plasminogen activator, the enzyme that activates the plasminogen that is a constituent of any serum. It is concluded that, to achieve wrapping of neurons by Schwann cells in culture, it is essential to have an active plasmin-generating system in the medium. It is hypothesized that the Schwann cell produces plasminogen activator. The possible role of both the Schwann cell and the plasminogen possible role of both the Schwann cell and the plasminogen activator in the formation of the neuromuscular junction is discussed."} {"id": "PMID:160560", "title": "DNA from recombinogenic lambda bacteriophages generated by arl mutant of Escherichia coli is cleaved by single-strand-specific endonuclease S1.", "content": "When propagated on arl strains (a subclass of Escherichia coli hyper-rec mutants), lambda \"Red-\" duplication phages accumulated an enhanced potential for recombination. The physical properties of the recombinogenic phages thus obtained (\"Arl-\" phages) were similar to those of phages grown on arl+ bacteria. However, Arl- phage DNA was cleaved by endonuclease S1 under conditions such that the nuclease is specific for single-stranded DNA;DNA from control phages was S1-resistant. The number of S1 sites (defined by the apparent decrease in single-strand molecular weight) reached a maximum (seven to nine sites per strand of lambda DNA) after five or six rounds of growth on arl bacteria. Similarly, the recombinogenicity of Arl- phages reached a limiting value (recombination frequency, 15%) that was 5 times that of Arl+ phages. Recombinogenicity and S1 susceptibility were accumulated concomitantly during growth on arl+ bacteria. If all increased recombination occurred at the S1 sites, then these regions (about 40 bases each) were about 300 times as recombinogenic as normal DNA regions of the same size, and 1.5 times as recombinogenic as UV-induced lesions. Chromosomal DNA and plasmid DNA (pBR322) from arl cells were more susceptible to nuclease S1 than was DNA from arl+ bacteria. Analysis of the cleavage products suggests that the S1 sites on Arl- lambda phage DNA are located randomly.", "contents": "DNA from recombinogenic lambda bacteriophages generated by arl mutant of Escherichia coli is cleaved by single-strand-specific endonuclease S1. When propagated on arl strains (a subclass of Escherichia coli hyper-rec mutants), lambda \"Red-\" duplication phages accumulated an enhanced potential for recombination. The physical properties of the recombinogenic phages thus obtained (\"Arl-\" phages) were similar to those of phages grown on arl+ bacteria. However, Arl- phage DNA was cleaved by endonuclease S1 under conditions such that the nuclease is specific for single-stranded DNA;DNA from control phages was S1-resistant. The number of S1 sites (defined by the apparent decrease in single-strand molecular weight) reached a maximum (seven to nine sites per strand of lambda DNA) after five or six rounds of growth on arl bacteria. Similarly, the recombinogenicity of Arl- phages reached a limiting value (recombination frequency, 15%) that was 5 times that of Arl+ phages. Recombinogenicity and S1 susceptibility were accumulated concomitantly during growth on arl+ bacteria. If all increased recombination occurred at the S1 sites, then these regions (about 40 bases each) were about 300 times as recombinogenic as normal DNA regions of the same size, and 1.5 times as recombinogenic as UV-induced lesions. Chromosomal DNA and plasmid DNA (pBR322) from arl cells were more susceptible to nuclease S1 than was DNA from arl+ bacteria. Analysis of the cleavage products suggests that the S1 sites on Arl- lambda phage DNA are located randomly."} {"id": "PMID:160561", "title": "DNA-directed in vitro synthesis of proteins involved in bacterial transcription and translation.", "content": "The in vitro synthesis of elongation factor (EF)-Tu (tufB), the beta beta' subunits of RNA polymerase, ribosomal proteins L10 and L12 directed by DNA from the transducing phage lambda rifd 18, EF-Tu (tufA), EF-G, and the alpha subunit of RNA polymerase directed by DNA from the transducing phage lambda fus3 has been investigated in a crude and a partially defined protein-synthesizing system. Proteins L10 and L12 are synthesized in the partially defined system almost as well as in the crude system. However, the synthesis of EF-Tu, EF-G, and the alpha and beta beta' subunits of RNA polymerase is far less efficient in the partially defined system. An active fraction that stimulates the synthesis of these latter proteins has been obtained by fractionation of a high-speed supernatant on DEAE-cellulose. Because previous studies showed that this fraction (1 M DEAE salt eluate) contains a protein, called L factor, that stimulates beta-galactosidase synthesis in vitro, L factor was tested for activity. Although L factor stimulates the synthesis of the beta beta' subunits, it has little or no effect on the in vitro synthesis of the other products studied. In the present experiments, the ratio of L12/L10 and of EF-Tu (tufA)/EF-G formed is 4-6. These values are consistent with in vivo results.", "contents": "DNA-directed in vitro synthesis of proteins involved in bacterial transcription and translation. The in vitro synthesis of elongation factor (EF)-Tu (tufB), the beta beta' subunits of RNA polymerase, ribosomal proteins L10 and L12 directed by DNA from the transducing phage lambda rifd 18, EF-Tu (tufA), EF-G, and the alpha subunit of RNA polymerase directed by DNA from the transducing phage lambda fus3 has been investigated in a crude and a partially defined protein-synthesizing system. Proteins L10 and L12 are synthesized in the partially defined system almost as well as in the crude system. However, the synthesis of EF-Tu, EF-G, and the alpha and beta beta' subunits of RNA polymerase is far less efficient in the partially defined system. An active fraction that stimulates the synthesis of these latter proteins has been obtained by fractionation of a high-speed supernatant on DEAE-cellulose. Because previous studies showed that this fraction (1 M DEAE salt eluate) contains a protein, called L factor, that stimulates beta-galactosidase synthesis in vitro, L factor was tested for activity. Although L factor stimulates the synthesis of the beta beta' subunits, it has little or no effect on the in vitro synthesis of the other products studied. In the present experiments, the ratio of L12/L10 and of EF-Tu (tufA)/EF-G formed is 4-6. These values are consistent with in vivo results."} {"id": "PMID:160562", "title": "Identification of the lexA gene product of Escherichia coli K-12.", "content": "The Escherichia coli lexA gene encodes a product important in induction of the recA gene and the expression of various cellular functions, including mutagenesis and prophage induction. As a start in a biochemical analysis of the lexA function, a family of lambda transducing phages carrying lexA+, lexA3, lexA3 spr-54, and lexA3 spr-55 alleles of the lexA gene was isolated and characterized. Polypeptides synthesized by these phages were examined. lambdalexA+ made a distinctive protein 24 kilodaltons (kd) in size. Lambda lexA3, which encodes an active mutant form of the protein dominant to wild-type function, made a slightly larger protein 25 kd in size. The latter protein was shown to be the mutant lexA3 gene product by the fact that lambda lexA3 spr-55, which carries an amber mutation in lexA3, made the 25-kd protein in hosts with an amber suppressor but not in a suppressor-free host. In hosts carrying a multicopy lexA3 plasmid, neither the 25-kd nor the 24-kd protein was made. This result suggests that lexA is autoregulated and that expression of the 24-kd protein made by lambda lexA+ is subject to the same controls. This and other evidence argues that the 24-kd protein is the product of the wild-type lexA+ gene.", "contents": "Identification of the lexA gene product of Escherichia coli K-12. The Escherichia coli lexA gene encodes a product important in induction of the recA gene and the expression of various cellular functions, including mutagenesis and prophage induction. As a start in a biochemical analysis of the lexA function, a family of lambda transducing phages carrying lexA+, lexA3, lexA3 spr-54, and lexA3 spr-55 alleles of the lexA gene was isolated and characterized. Polypeptides synthesized by these phages were examined. lambdalexA+ made a distinctive protein 24 kilodaltons (kd) in size. Lambda lexA3, which encodes an active mutant form of the protein dominant to wild-type function, made a slightly larger protein 25 kd in size. The latter protein was shown to be the mutant lexA3 gene product by the fact that lambda lexA3 spr-55, which carries an amber mutation in lexA3, made the 25-kd protein in hosts with an amber suppressor but not in a suppressor-free host. In hosts carrying a multicopy lexA3 plasmid, neither the 25-kd nor the 24-kd protein was made. This result suggests that lexA is autoregulated and that expression of the 24-kd protein made by lambda lexA+ is subject to the same controls. This and other evidence argues that the 24-kd protein is the product of the wild-type lexA+ gene."} {"id": "PMID:160563", "title": "The delta subunit of Escherichia coli DNA polymerase III holoenzyme is the dnaX gene product.", "content": "The delta subunit of DNA polymerase III holoenzyme has been purified extensively with an assay for phi X174 DNA synthesis using core (pol III) and beta and gamma subunits. Either the purified delta subunit or the purified DNA polymerase III holoenzyme can complement a defective enzyme fraction from the conditional replication mutant SG133 described by Sevastopoulos et al. [Sevastopoulas, C.G., Wehr, C.T. & Glaser, D. A. (1977) Proc. Natl. Acad. Sci. USA 74, 3485-3489]. It has been established by Henson et al. [Henson, J.M., Chu, H., Irwin, C.A. & Walker, J.R. (1979) Genetics 92, 1,41-1059] that SG133 has two temperature-sensitive mutations, called dnaX and dnaY. The crude enzyme source from dnaX can be complemented by the delta subunit and by DNA polymerase III holoenzyme. By contrast, the core DNA polymerase III and the beta and gamma subunits are unable to complement this defective enzyme fraction. Thus, the delta subunit of DNA polymerase III holoenzyme appears to be the dnaX gene product of Escherichia coli.", "contents": "The delta subunit of Escherichia coli DNA polymerase III holoenzyme is the dnaX gene product. The delta subunit of DNA polymerase III holoenzyme has been purified extensively with an assay for phi X174 DNA synthesis using core (pol III) and beta and gamma subunits. Either the purified delta subunit or the purified DNA polymerase III holoenzyme can complement a defective enzyme fraction from the conditional replication mutant SG133 described by Sevastopoulos et al. [Sevastopoulas, C.G., Wehr, C.T. & Glaser, D. A. (1977) Proc. Natl. Acad. Sci. USA 74, 3485-3489]. It has been established by Henson et al. [Henson, J.M., Chu, H., Irwin, C.A. & Walker, J.R. (1979) Genetics 92, 1,41-1059] that SG133 has two temperature-sensitive mutations, called dnaX and dnaY. The crude enzyme source from dnaX can be complemented by the delta subunit and by DNA polymerase III holoenzyme. By contrast, the core DNA polymerase III and the beta and gamma subunits are unable to complement this defective enzyme fraction. Thus, the delta subunit of DNA polymerase III holoenzyme appears to be the dnaX gene product of Escherichia coli."} {"id": "PMID:160564", "title": "Fluctuations in polarized fluorescence: evidence that muscle cross bridges rotate repetitively during contraction.", "content": "Particular thiols of the myosin subfragment 1 moieties of single glycerinated muscle fibers are covalently labeled with rhodamine. By using appropriate solutions such fibers can be relaxed, be in rigor, or develop active isometric tension. The rhodamine is excited by polarized 514.5-nm laser light; the greater than 580-nm fluorescence is resolved into orthogonal components and the intensity of each is measured by a computer-interfaced photon counting system. Fluctuations over-and-above noise appear in steady-state activity but not in relaxation or rigor and not when the fluorophore is actin-attached instead of myosin-attached. Fluctuations also appear in ratios of polarized intensities--quantities sensitive to fluorophore attitude but not to fluorophore number. The fluctuations are dominated by low (approximately 2 Hz) frequencies similar to separately measured ATPase frequencies. The fluctuations are ascribed to repetitive motion of the cross bridges to which the rhodamine is attached.", "contents": "Fluctuations in polarized fluorescence: evidence that muscle cross bridges rotate repetitively during contraction. Particular thiols of the myosin subfragment 1 moieties of single glycerinated muscle fibers are covalently labeled with rhodamine. By using appropriate solutions such fibers can be relaxed, be in rigor, or develop active isometric tension. The rhodamine is excited by polarized 514.5-nm laser light; the greater than 580-nm fluorescence is resolved into orthogonal components and the intensity of each is measured by a computer-interfaced photon counting system. Fluctuations over-and-above noise appear in steady-state activity but not in relaxation or rigor and not when the fluorophore is actin-attached instead of myosin-attached. Fluctuations also appear in ratios of polarized intensities--quantities sensitive to fluorophore attitude but not to fluorophore number. The fluctuations are dominated by low (approximately 2 Hz) frequencies similar to separately measured ATPase frequencies. The fluctuations are ascribed to repetitive motion of the cross bridges to which the rhodamine is attached."} {"id": "PMID:160565", "title": "Presence of calmodulin in Tetrahymena.", "content": "Ca-dependent affinity chromatography on phenothiazine-Sepharose 4B has been used to isolate a pure protein from the ciliate Tetrahymena pyriformis. This protein has been identified as calmodulin by demonstrating three of the Ca-dependent activities attributed to calmodulins. Tetrahymena calmodulin also has physicochemical properties similar to those of the previously characterized mammalian, coelenterate, and plant proteins, except for a lower molecular weight (15,000) and slightly different CNBr fragments compared to bovine brain calmodulin. Calmodulin is a constituent of demembranated Tetrahymena cilia from which it can be extracted with the crude dynein fraction. Sucrose density gradient fractionation indicated its presence in fractions containing the 14S dynein ATPase. It is concluded that the essential properties of calmodulin have been highly conserved during much of eukaryotic evolution, and it is suggested that calmodulin plays a role in the control of ciliary motility in Tetrahymena.", "contents": "Presence of calmodulin in Tetrahymena. Ca-dependent affinity chromatography on phenothiazine-Sepharose 4B has been used to isolate a pure protein from the ciliate Tetrahymena pyriformis. This protein has been identified as calmodulin by demonstrating three of the Ca-dependent activities attributed to calmodulins. Tetrahymena calmodulin also has physicochemical properties similar to those of the previously characterized mammalian, coelenterate, and plant proteins, except for a lower molecular weight (15,000) and slightly different CNBr fragments compared to bovine brain calmodulin. Calmodulin is a constituent of demembranated Tetrahymena cilia from which it can be extracted with the crude dynein fraction. Sucrose density gradient fractionation indicated its presence in fractions containing the 14S dynein ATPase. It is concluded that the essential properties of calmodulin have been highly conserved during much of eukaryotic evolution, and it is suggested that calmodulin plays a role in the control of ciliary motility in Tetrahymena."} {"id": "PMID:160566", "title": "Gene for the RNA polymerase sigma subunit mapped in Salmonella typhimurium and Escherichia coli by cloning and deletion.", "content": "The genes for the RNA polymerase sigma subunit (rpoD) and DNA primase (dnaG) of Salmonella typhimurium have been cloned into lambda vectors. Combined restriction, deletion and functional analysis of the cloned fragment allows us to map the genes precisely on the fragment, establishes the direction in which rpoD is transcribed, and reveals the existence of at least one new gene in the vicinity. A closely homologous, smaller fragment of Escherichia coli DNA, also cloned into lambda, contains rpoD and at least part of dnaG.", "contents": "Gene for the RNA polymerase sigma subunit mapped in Salmonella typhimurium and Escherichia coli by cloning and deletion. The genes for the RNA polymerase sigma subunit (rpoD) and DNA primase (dnaG) of Salmonella typhimurium have been cloned into lambda vectors. Combined restriction, deletion and functional analysis of the cloned fragment allows us to map the genes precisely on the fragment, establishes the direction in which rpoD is transcribed, and reveals the existence of at least one new gene in the vicinity. A closely homologous, smaller fragment of Escherichia coli DNA, also cloned into lambda, contains rpoD and at least part of dnaG."} {"id": "PMID:160567", "title": "Operon-specific regulation of ribosomal protein synthesis in Escherichia coli.", "content": "We have cloned a DNA fragment harboring the genes for ribosomal proteins L2, L4, and L23 on a plasmid vector that contains a lac operator and promoter. The cloned ribosomal protein genes are now under the control of lacOP. Addition of a lac inducer to these cells results in a specific 5- to 10-fold increase in the synthesis of the proteins corresponding to the cloned genes. Within 10 min of this induction, the synthesis of ribosomal proteins S3, S19, L3, L16, L22, and L29 stops almost completely. The genes for all these proteins reside in the same chromosomal operon as L2, L4, and L23. We have seen no dramatic effect on the synthesis of any other ribosomal proteins. Thus, the induction of L2, L4, and L23 results in a specific and rapid decrease in the expression of all (or almost all) genes in their own transcription unit.", "contents": "Operon-specific regulation of ribosomal protein synthesis in Escherichia coli. We have cloned a DNA fragment harboring the genes for ribosomal proteins L2, L4, and L23 on a plasmid vector that contains a lac operator and promoter. The cloned ribosomal protein genes are now under the control of lacOP. Addition of a lac inducer to these cells results in a specific 5- to 10-fold increase in the synthesis of the proteins corresponding to the cloned genes. Within 10 min of this induction, the synthesis of ribosomal proteins S3, S19, L3, L16, L22, and L29 stops almost completely. The genes for all these proteins reside in the same chromosomal operon as L2, L4, and L23. We have seen no dramatic effect on the synthesis of any other ribosomal proteins. Thus, the induction of L2, L4, and L23 results in a specific and rapid decrease in the expression of all (or almost all) genes in their own transcription unit."} {"id": "PMID:160568", "title": "Impairment of antigen-presenting cell function by ultraviolet radiation.", "content": "UV light irradiation of BALB/c mice was found to result in impairment of antigen-presenting cell function. Adherent trinitrophenyl-derivatized cells from the peritoneal exudate cell population or the spleen of UV-treated donors could not induce hapten-specific delayed hypersensitivity responses in UV-irradiated syngeneic mice, whereas adherent trinitrophenyl-derivatized cells from normal mice were able to do so. The failure to induce immunity in UV-treated mice by utilizing UV-treated adherent antigen-presenting cells was associated with the development of antigen-specific suppressor T cells. The implication of these results for UV-induced carcinogenesis is discussed.", "contents": "Impairment of antigen-presenting cell function by ultraviolet radiation. UV light irradiation of BALB/c mice was found to result in impairment of antigen-presenting cell function. Adherent trinitrophenyl-derivatized cells from the peritoneal exudate cell population or the spleen of UV-treated donors could not induce hapten-specific delayed hypersensitivity responses in UV-irradiated syngeneic mice, whereas adherent trinitrophenyl-derivatized cells from normal mice were able to do so. The failure to induce immunity in UV-treated mice by utilizing UV-treated adherent antigen-presenting cells was associated with the development of antigen-specific suppressor T cells. The implication of these results for UV-induced carcinogenesis is discussed."} {"id": "PMID:160569", "title": "Influence of PCPA, shock level, and home-cage conditions on shock-induced aggression.", "content": "In a series of experiments, the effect of parachlorophenylalanine (PCPA) on shock-induced fighting was assessed rats raised and maintained under either a 12-hr alternating light-dark cycle (LD) or constant light conditions (LL). PCPA increased shock-induced aggression only in LL groups when testing was accomplished using a 2 mA shock; PCPA resulted in increased aggression in groups from the LD condition only when testing was done at 1 mA. A procedure that used castrated and intact cagemates to manipulate home-cage social experience provided evidence for a role for social experience in determining differences between LL and LD reared rats in shock-induced aggression. However, these data also suggested that home-cage social experience was not a factor in the lighting condition influence on the effect of PCPA on shock-induced aggression. Finally, a separate experiment demonstrated that diurnal rhythms in shock-induced aggression were disrupted by handling and vehicle injection in the control procedures, so the possible role of serotonin in diurnal rhythms of aggression behavior could not be assessed.", "contents": "Influence of PCPA, shock level, and home-cage conditions on shock-induced aggression. In a series of experiments, the effect of parachlorophenylalanine (PCPA) on shock-induced fighting was assessed rats raised and maintained under either a 12-hr alternating light-dark cycle (LD) or constant light conditions (LL). PCPA increased shock-induced aggression only in LL groups when testing was accomplished using a 2 mA shock; PCPA resulted in increased aggression in groups from the LD condition only when testing was done at 1 mA. A procedure that used castrated and intact cagemates to manipulate home-cage social experience provided evidence for a role for social experience in determining differences between LL and LD reared rats in shock-induced aggression. However, these data also suggested that home-cage social experience was not a factor in the lighting condition influence on the effect of PCPA on shock-induced aggression. Finally, a separate experiment demonstrated that diurnal rhythms in shock-induced aggression were disrupted by handling and vehicle injection in the control procedures, so the possible role of serotonin in diurnal rhythms of aggression behavior could not be assessed."} {"id": "PMID:160570", "title": "Effect of isatin (2,3-dioxoindoline) on audiogenic seizures in rats and its relationship to electrographic and behavioural phenomena.", "content": "In doses of 160 and 80 mg/kg, isatin (2,3-dioxoindoline) significantly reduced the total incidence of audiogenic epileptic seizures in rats highly sensitive to an acoustic epileptogenic stimulus. The number of severest forms of seizure (running, clonic convulsions) was higher than in the control tests, however. The acoustic epileptogenic stimuls was applied one hour after the i.p. injection of isatin. At that time some postural reflexes were still inhibited after 160 mg isatin/kg, while after smaller doses they were already normal again. One hour after administering isatin there were marked changes in the electroencephalogram, the chief ones being an increase in rhythmic episodic activity against a desynchronization background and a decrease in slow wave sleep activity.", "contents": "Effect of isatin (2,3-dioxoindoline) on audiogenic seizures in rats and its relationship to electrographic and behavioural phenomena. In doses of 160 and 80 mg/kg, isatin (2,3-dioxoindoline) significantly reduced the total incidence of audiogenic epileptic seizures in rats highly sensitive to an acoustic epileptogenic stimulus. The number of severest forms of seizure (running, clonic convulsions) was higher than in the control tests, however. The acoustic epileptogenic stimuls was applied one hour after the i.p. injection of isatin. At that time some postural reflexes were still inhibited after 160 mg isatin/kg, while after smaller doses they were already normal again. One hour after administering isatin there were marked changes in the electroencephalogram, the chief ones being an increase in rhythmic episodic activity against a desynchronization background and a decrease in slow wave sleep activity."} {"id": "PMID:160571", "title": "A study of intestinal dipeptidases of rats: effect of in vivo mucosal exposure to vinblastine.", "content": "The mucosal population of small intestine of rats was exposed in vivo to various concentrations of vinblastine sulfate for 30 and 60 min and the activities of glycyl-L-valine and glycyl-L-leucine hydrolase were measured in the treated mucosa of the upper jejunal segment. A significant depression in the activity of these dipeptidases was observed which was further found to be dose dependent.", "contents": "A study of intestinal dipeptidases of rats: effect of in vivo mucosal exposure to vinblastine. The mucosal population of small intestine of rats was exposed in vivo to various concentrations of vinblastine sulfate for 30 and 60 min and the activities of glycyl-L-valine and glycyl-L-leucine hydrolase were measured in the treated mucosa of the upper jejunal segment. A significant depression in the activity of these dipeptidases was observed which was further found to be dose dependent."} {"id": "PMID:160573", "title": "Effect of flavonoids on vitamin C activity of D-isoascorbic acid.", "content": "Large peroral doses of D-isoascorbic acid, a vitamin C stereoisomer (50 mg per animal per day), were retained in the guinea-pig organism to a smaller extent than the same doses of L-ascorbic acid (vitamin C). Simultaneous administration of the flavonoids rutin and epicatechin increased the amount of D-isoascorbic acid retained in the liver, brain and wall of the small intestine by up to 100%, but four weeks after its extraction from the food the amount of L-ascorbic acid left in the guinea-pig organism still exceeded D-isoascorbic acid reserves. This difference, which was found in all the organs studied, was the largest in the groups simultaneously given flavonoids. In guinea-pigs which, like man, are dependent on an exogenous vitamin C supply, D-isoascorbic acid was metabolized at a manifestly higher rate than L-ascorbic acid, irrespective of whether flavonoids were administered or not. In liver, brain and small intestine wall homogenates, the oxidized forms of both stereoisomers were reduced in the presence of reduced glutathione, but the reduction rate of D-isodehydroascorbic acid was higher and it was stimulated by the two flavonoids more strongly than the reduction of L-dehydroascorbic acid. The stuterospecific.", "contents": "Effect of flavonoids on vitamin C activity of D-isoascorbic acid. Large peroral doses of D-isoascorbic acid, a vitamin C stereoisomer (50 mg per animal per day), were retained in the guinea-pig organism to a smaller extent than the same doses of L-ascorbic acid (vitamin C). Simultaneous administration of the flavonoids rutin and epicatechin increased the amount of D-isoascorbic acid retained in the liver, brain and wall of the small intestine by up to 100%, but four weeks after its extraction from the food the amount of L-ascorbic acid left in the guinea-pig organism still exceeded D-isoascorbic acid reserves. This difference, which was found in all the organs studied, was the largest in the groups simultaneously given flavonoids. In guinea-pigs which, like man, are dependent on an exogenous vitamin C supply, D-isoascorbic acid was metabolized at a manifestly higher rate than L-ascorbic acid, irrespective of whether flavonoids were administered or not. In liver, brain and small intestine wall homogenates, the oxidized forms of both stereoisomers were reduced in the presence of reduced glutathione, but the reduction rate of D-isodehydroascorbic acid was higher and it was stimulated by the two flavonoids more strongly than the reduction of L-dehydroascorbic acid. The stuterospecific."} {"id": "PMID:160574", "title": "Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.", "content": "Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.", "contents": "Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions. Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible."} {"id": "PMID:160575", "title": "Electrophysiological analysis of retrieval of conditioned taste aversion. Physiological techniques and data processing.", "content": "New techniques suitable for electrophysiological investigation of retrieval of conditioned taste aversion (CTA) were developed. The gustatory discrimination apparatus consisted of two parallel drinking spouts (20 mm apart) equipped with photoelectric lick sensors. The spouts contained water or the aversive fluid (0.15 M LiCl), respectively, and their position could be rapidly (50 ms) interchanged with a reversive electromotor. Licking at either spout and the position of the fluids were recorded on one channel of a tape recorder. Unit activity was picked up with tungsten microelectrodes (40 micrometers) inserted into the brain of a freely moving rat with a head-mounted microdrive system (weight 2 g), fixed to an implanted guiding cannula. The electrode was connected through a head-carried FET signal follower to a wide band integrated circuit amplifier and the unit activity was recorded in the other channel of the tape recorder. The records were evaluated using an off-line computer program (LINC 8) consisting of a spike detection subroutine followed by amplitude histogram analysis. The mean (M) and SD values were computed for uni- or bimodal amplitude distributions of the principal spike components. Spike falling within the M+/-2 SD range of the selected parameter were identified as single units and used for construction of post stimulus histograms triggered by licking or by spout switching.", "contents": "Electrophysiological analysis of retrieval of conditioned taste aversion. Physiological techniques and data processing. New techniques suitable for electrophysiological investigation of retrieval of conditioned taste aversion (CTA) were developed. The gustatory discrimination apparatus consisted of two parallel drinking spouts (20 mm apart) equipped with photoelectric lick sensors. The spouts contained water or the aversive fluid (0.15 M LiCl), respectively, and their position could be rapidly (50 ms) interchanged with a reversive electromotor. Licking at either spout and the position of the fluids were recorded on one channel of a tape recorder. Unit activity was picked up with tungsten microelectrodes (40 micrometers) inserted into the brain of a freely moving rat with a head-mounted microdrive system (weight 2 g), fixed to an implanted guiding cannula. The electrode was connected through a head-carried FET signal follower to a wide band integrated circuit amplifier and the unit activity was recorded in the other channel of the tape recorder. The records were evaluated using an off-line computer program (LINC 8) consisting of a spike detection subroutine followed by amplitude histogram analysis. The mean (M) and SD values were computed for uni- or bimodal amplitude distributions of the principal spike components. Spike falling within the M+/-2 SD range of the selected parameter were identified as single units and used for construction of post stimulus histograms triggered by licking or by spout switching."} {"id": "PMID:160576", "title": "Urease activity in the contents and tissues of the sheep, pig and chicken gastrointestinal apparatus.", "content": "Urease activity, expressed as mg N-NH3/g dry weight per 30 min at 25 degrees C, was determined in the various parts of the sheep, chicken and pig digestive apparatus. The results were as follows. Sheep: contents--rumen 1.25\"/-0.09, reticulum 0.78+/-0.02, omasum 0.44+/-0.02, abomasum 0.002+/-0.001, duodenum 0.003+/-0.001, jejunum 0.18+/-0.03, ileum 0.42+/-0.03, caecum 1.34+/-0.11, colon 0.76+/-0.08, walls-rumen 0.88+/-0.16, reticulum 0.38+/-0.04, omasum 0.11+/-0.02, abomasum 0.01+/-0.002, ileum 0.092+/-0.01, caecum 0.14+/-0.03, colon 0.16+/-0.02. Chicken: contents--jejunum 0.028+/-0.009, ileum 0.043+/-0.013, caecum 0.17+/-0.03, colon and cloaca 0.04+/-0.013. Pigs: contents--jejunum 0.02+/-0.01, ileum 0.14+/-0.08, caecum 0.62+-0.12, colon 0.43+/-0.06. No urease activity was found in the walls of the digestive apparatus or the contents of the duodenum in chickens, or in the walls of the stomach and intestine and the contents of the duodenum in pigs. The results show that urease activity in the digestive apparatus of pigs and poultry is lower than in sheep. Inadequate urease activity in the digestive apparatus explains why chickens and pigs are significantly less capable than ruminants of utilizing urea nitrogen as a substitute for some of the protein in the diet.", "contents": "Urease activity in the contents and tissues of the sheep, pig and chicken gastrointestinal apparatus. Urease activity, expressed as mg N-NH3/g dry weight per 30 min at 25 degrees C, was determined in the various parts of the sheep, chicken and pig digestive apparatus. The results were as follows. Sheep: contents--rumen 1.25\"/-0.09, reticulum 0.78+/-0.02, omasum 0.44+/-0.02, abomasum 0.002+/-0.001, duodenum 0.003+/-0.001, jejunum 0.18+/-0.03, ileum 0.42+/-0.03, caecum 1.34+/-0.11, colon 0.76+/-0.08, walls-rumen 0.88+/-0.16, reticulum 0.38+/-0.04, omasum 0.11+/-0.02, abomasum 0.01+/-0.002, ileum 0.092+/-0.01, caecum 0.14+/-0.03, colon 0.16+/-0.02. Chicken: contents--jejunum 0.028+/-0.009, ileum 0.043+/-0.013, caecum 0.17+/-0.03, colon and cloaca 0.04+/-0.013. Pigs: contents--jejunum 0.02+/-0.01, ileum 0.14+/-0.08, caecum 0.62+-0.12, colon 0.43+/-0.06. No urease activity was found in the walls of the digestive apparatus or the contents of the duodenum in chickens, or in the walls of the stomach and intestine and the contents of the duodenum in pigs. The results show that urease activity in the digestive apparatus of pigs and poultry is lower than in sheep. Inadequate urease activity in the digestive apparatus explains why chickens and pigs are significantly less capable than ruminants of utilizing urea nitrogen as a substitute for some of the protein in the diet."} {"id": "PMID:160577", "title": "Endogenous urea secretion into the sheep gastrointestinal tract.", "content": "Urea turnover and the proportion of endogenous urea secreted and excreted in the saliva, the bile, the pancreatic juice and the urine and directly across the wall of the digestive tract was studied in 6 experiments, after a single i.v. dose of labelled 15N, in two adult sheep weighing 49 and 50 kg, with permanent biliary and pancreatic fistulus and with an exteriorized right parotid duct. It was found that, of the total amount of endogenous urea secreted into the animals' digestive tract (0.2694+/-0.0138 mg/min/kg b.w.), 10.27+/-0.94% reached the contents in the saliva, 2.12+/-0.28% in the bile and 0.66+/-0.08% in the pancreatic juice, and that 86.95+/-2.1% was secreted into the gastrointestinal tract, across its wall, from the blood capillaries. Exogenous turnover amounted to 0.3228+/-0.192 mg/min/kg. Of the total amount of 476.6 mg i.v. injected 15N urea, 274.1+/-8.86 mg was excreted in the urine 5.1+/-0.9 mg in the bile, 3.19+/-0.06 mg in the pancreatic juice, 4.96+/-0.76 mg via the right parotid gland and 9.34+/-1.09 mg in the faeces. The results show that the quantitatively most important part of the recirculation of endogenous urea is its passage from the blood across the wall of the gastrointestinal tract into its contents.", "contents": "Endogenous urea secretion into the sheep gastrointestinal tract. Urea turnover and the proportion of endogenous urea secreted and excreted in the saliva, the bile, the pancreatic juice and the urine and directly across the wall of the digestive tract was studied in 6 experiments, after a single i.v. dose of labelled 15N, in two adult sheep weighing 49 and 50 kg, with permanent biliary and pancreatic fistulus and with an exteriorized right parotid duct. It was found that, of the total amount of endogenous urea secreted into the animals' digestive tract (0.2694+/-0.0138 mg/min/kg b.w.), 10.27+/-0.94% reached the contents in the saliva, 2.12+/-0.28% in the bile and 0.66+/-0.08% in the pancreatic juice, and that 86.95+/-2.1% was secreted into the gastrointestinal tract, across its wall, from the blood capillaries. Exogenous turnover amounted to 0.3228+/-0.192 mg/min/kg. Of the total amount of 476.6 mg i.v. injected 15N urea, 274.1+/-8.86 mg was excreted in the urine 5.1+/-0.9 mg in the bile, 3.19+/-0.06 mg in the pancreatic juice, 4.96+/-0.76 mg via the right parotid gland and 9.34+/-1.09 mg in the faeces. The results show that the quantitatively most important part of the recirculation of endogenous urea is its passage from the blood across the wall of the gastrointestinal tract into its contents."} {"id": "PMID:160578", "title": "Postnatal development of postganglionic parasympathetic neurones in the heart of the albino rat.", "content": "Electrical stimulation of the sinoatrial node region of isolated atria in medium containing physostigmine (0.1 micrograms/ml) produces a negative chronotropic effect whose intensity and duration depend mainly on the amount of acetylcholine released from postganglionic parasympathetic fibres endings. This technique was used to study functional maturation of the given neurones during postnatal development of albino rats. Preparations from animals of different ages were stimulated with 2-second bursts of rectangular pulses (frequency 50 Hz, pulse duration 0.02 ms, voltage 22.5--27.5 V) and frequency changes of the preparation were registered by recording extracellular action potentials. At 10 days the negative chronotropic effect is very weak and at 15 days it is only slightly stronger, but at 18 days it is almost the same as in adult animals. At 24 and 34 days the reaction is somewhat stronger than in adulthood. It can be concluded from these observations that functional maturation of the postganglionic parasympathetic neurones innervating the sinoatrial node in albino rats occurs between the 10th and 20th day of postnatal life.", "contents": "Postnatal development of postganglionic parasympathetic neurones in the heart of the albino rat. Electrical stimulation of the sinoatrial node region of isolated atria in medium containing physostigmine (0.1 micrograms/ml) produces a negative chronotropic effect whose intensity and duration depend mainly on the amount of acetylcholine released from postganglionic parasympathetic fibres endings. This technique was used to study functional maturation of the given neurones during postnatal development of albino rats. Preparations from animals of different ages were stimulated with 2-second bursts of rectangular pulses (frequency 50 Hz, pulse duration 0.02 ms, voltage 22.5--27.5 V) and frequency changes of the preparation were registered by recording extracellular action potentials. At 10 days the negative chronotropic effect is very weak and at 15 days it is only slightly stronger, but at 18 days it is almost the same as in adult animals. At 24 and 34 days the reaction is somewhat stronger than in adulthood. It can be concluded from these observations that functional maturation of the postganglionic parasympathetic neurones innervating the sinoatrial node in albino rats occurs between the 10th and 20th day of postnatal life."} {"id": "PMID:160579", "title": "Postnatal changes in the amount of acetylcholine in the atrial tissue of the albino rat heart.", "content": "Changes in the acetylcholine (ACh) content and concentration in the atrial tissue of albino rats between the third day of postnatal life and adulthood were studied. The ACh content (ng in whole atria) rose during the whole of the period in question, from 5.6 ng at 3--4 days to 307.5 ng in adult rats. The ACh concentration (micrograms/g fresh tissue) rose up to the 53rd day after birth, when it attained adult values. The fastest increase in both the ACh content and concentration was observed between the 10th and the 17th postnatal day, when it amounted to over 46% of the total concentration increase between the third day of life and adulthood.", "contents": "Postnatal changes in the amount of acetylcholine in the atrial tissue of the albino rat heart. Changes in the acetylcholine (ACh) content and concentration in the atrial tissue of albino rats between the third day of postnatal life and adulthood were studied. The ACh content (ng in whole atria) rose during the whole of the period in question, from 5.6 ng at 3--4 days to 307.5 ng in adult rats. The ACh concentration (micrograms/g fresh tissue) rose up to the 53rd day after birth, when it attained adult values. The fastest increase in both the ACh content and concentration was observed between the 10th and the 17th postnatal day, when it amounted to over 46% of the total concentration increase between the third day of life and adulthood."} {"id": "PMID:160584", "title": "Postoperative causes of death of neonatal intestinal obstruction excluding mucoviscidosis and Hirschsprung's disease.", "content": "In contrast to the remarkable improvement in the results of operations for oesophageal atresia at the University Children's Hospital, Zurich, the death rate secondary to operations for neonatal intestinal obstruction has remained constantly high between the years 1960 and 1976. The results are distressing especially when it is realised that many of them occurred in infants with good general conditions. The causes of death are analysed and classified according the following criteria: 1. Deaths associated with trisomy 21. 2. Deaths due to the short gut syndrome. 3. Deaths due to severe associated malformations or other conditions. 4. Deaths probably due to surgical mistakes. 5. Deaths due to mistakes in management. The latter group can be subdivided further in deaths due to wrong decision at the primary operation, overlooked medical complications, overlooked surgical complications and mistakes made at subsequent laparotomies.", "contents": "Postoperative causes of death of neonatal intestinal obstruction excluding mucoviscidosis and Hirschsprung's disease. In contrast to the remarkable improvement in the results of operations for oesophageal atresia at the University Children's Hospital, Zurich, the death rate secondary to operations for neonatal intestinal obstruction has remained constantly high between the years 1960 and 1976. The results are distressing especially when it is realised that many of them occurred in infants with good general conditions. The causes of death are analysed and classified according the following criteria: 1. Deaths associated with trisomy 21. 2. Deaths due to the short gut syndrome. 3. Deaths due to severe associated malformations or other conditions. 4. Deaths probably due to surgical mistakes. 5. Deaths due to mistakes in management. The latter group can be subdivided further in deaths due to wrong decision at the primary operation, overlooked medical complications, overlooked surgical complications and mistakes made at subsequent laparotomies."} {"id": "PMID:160585", "title": "Gastroschisis and omphalocele.", "content": "A series of 100 patients with gastroschisis and omphalocele is presented. It is emphasized that gastroschisis generally has a strikingly homogeneous clinical presentation, while the omphalocele has a more heterogeneous clinical presentation, varying from the smallest to the largest, nearly incorrectable type. The main problem in the two groups is the problem of the closure of the defect. In gastroschisis there are, in addition, two problems related to the length of the intestinal tract and the tendency to peritonitis and septicaemia. In omphalocele, however, the major problem is the associated anomalies. The experience from the present material indicates that greater efforts must be used in the future in trying to avoid hypothermia, both during transportation and during operation. Furthermore, greater efforts must be made in closing the abdominal wall defect primarily in both groups of patients. More liberal use of respirator and total parenteral nutrition, mainly by peripheral veins, has obviously contributed to the improvement in our results from 1 60% mortality rate in the first nine-year period to a 37% mortality rate in the last nine-year period in the omphalocele group. Our best results have been obtained during the last 3 years with 2 deaths in the last 12 patients who all were treated by primary closure. In the gastroschisis group a survival rate of 69% in the whole series and of 74% in those who were primarily completely closed must be looked upon as progress in the light of earlier reports of survival rates of 36% to 43%.", "contents": "Gastroschisis and omphalocele. A series of 100 patients with gastroschisis and omphalocele is presented. It is emphasized that gastroschisis generally has a strikingly homogeneous clinical presentation, while the omphalocele has a more heterogeneous clinical presentation, varying from the smallest to the largest, nearly incorrectable type. The main problem in the two groups is the problem of the closure of the defect. In gastroschisis there are, in addition, two problems related to the length of the intestinal tract and the tendency to peritonitis and septicaemia. In omphalocele, however, the major problem is the associated anomalies. The experience from the present material indicates that greater efforts must be used in the future in trying to avoid hypothermia, both during transportation and during operation. Furthermore, greater efforts must be made in closing the abdominal wall defect primarily in both groups of patients. More liberal use of respirator and total parenteral nutrition, mainly by peripheral veins, has obviously contributed to the improvement in our results from 1 60% mortality rate in the first nine-year period to a 37% mortality rate in the last nine-year period in the omphalocele group. Our best results have been obtained during the last 3 years with 2 deaths in the last 12 patients who all were treated by primary closure. In the gastroschisis group a survival rate of 69% in the whole series and of 74% in those who were primarily completely closed must be looked upon as progress in the light of earlier reports of survival rates of 36% to 43%."} {"id": "PMID:160586", "title": "Causes of postoperative deaths in gastroschisis and omphalocele.", "content": "Improvement in treatment should reduce the mortality of infants with gastroschisis and omphalocele which is still high and is mainly due to septic complications. The mortality in infants who have additional severe malformations may be difficult to improve, and one should hesitate to treat such additional anomalies which are incompatible with life and which even when treated may cause permanent severe defects.", "contents": "Causes of postoperative deaths in gastroschisis and omphalocele. Improvement in treatment should reduce the mortality of infants with gastroschisis and omphalocele which is still high and is mainly due to septic complications. The mortality in infants who have additional severe malformations may be difficult to improve, and one should hesitate to treat such additional anomalies which are incompatible with life and which even when treated may cause permanent severe defects."} {"id": "PMID:160589", "title": "Effects of PGI2 on the inactivation of thrombin, factor Xa, and plasmin by antithrombin-III and heparin.", "content": "The influence of PGI2 on the activity and on the inactivation of enzymes participating in blood coagulation (thrombin and Factor Xa) and fibrinolysis (plasmin) were investigated. According to the results PGI2 has no effect on the activity of Factor Xa and plasmin nor on the inactivation of these enzymes by antithrombin-III in the absence and presence of heparin at a concentration of PGI2 up to 400 micrograms/ml. An acceleration of the inactivation of thrombin by antithormbin-III was found in the presence of PGI2 within a concentration of 100-400 micrograms/ml without any effect on the heparin-accelerated inactivation of thrombin by antithrombin. We got similar results using clotting tests for the assay and the application of synthetic substrate for thrombin. This inactivation-accelerating effect of PGI2 on thrombin was only demonstratable at a concentration five magnitudes higher than that of the anti-aggregation effect on platelets.", "contents": "Effects of PGI2 on the inactivation of thrombin, factor Xa, and plasmin by antithrombin-III and heparin. The influence of PGI2 on the activity and on the inactivation of enzymes participating in blood coagulation (thrombin and Factor Xa) and fibrinolysis (plasmin) were investigated. According to the results PGI2 has no effect on the activity of Factor Xa and plasmin nor on the inactivation of these enzymes by antithrombin-III in the absence and presence of heparin at a concentration of PGI2 up to 400 micrograms/ml. An acceleration of the inactivation of thrombin by antithormbin-III was found in the presence of PGI2 within a concentration of 100-400 micrograms/ml without any effect on the heparin-accelerated inactivation of thrombin by antithrombin. We got similar results using clotting tests for the assay and the application of synthetic substrate for thrombin. This inactivation-accelerating effect of PGI2 on thrombin was only demonstratable at a concentration five magnitudes higher than that of the anti-aggregation effect on platelets."} {"id": "PMID:160609", "title": "Evaluation of the microsphere-method for determination of cardiac output.", "content": "Cardiac output was determined by means of radioactive microspheres, 15 +/- 5 microns in diameter. Blood flow in the ascending aorta was measured by an electromagnetic flowmeter. In eight cats thirty-eight simultaneous measurements were made of cardiac output and aortic flow. The observations correlated well (r = 0.89), with a mean difference of 5.2%, probably corresponding to coronary blood flow. Continuous flow recordings showed no alterations in aortic flow during the injections of microspheres; arterial blood pressure and heart rate remained unchanged even after six injections, each consisting of about 2 x 10(5) spheres per kg body weight. Tests for shunting of microspheres were performed and revealed shunt fractions in the systemic circulation of about 8%, with no significant shunting through the lungs. The microsphere method for determining cardiac output is thought to be an accurate method, suitable for small and medium sized animals.", "contents": "Evaluation of the microsphere-method for determination of cardiac output. Cardiac output was determined by means of radioactive microspheres, 15 +/- 5 microns in diameter. Blood flow in the ascending aorta was measured by an electromagnetic flowmeter. In eight cats thirty-eight simultaneous measurements were made of cardiac output and aortic flow. The observations correlated well (r = 0.89), with a mean difference of 5.2%, probably corresponding to coronary blood flow. Continuous flow recordings showed no alterations in aortic flow during the injections of microspheres; arterial blood pressure and heart rate remained unchanged even after six injections, each consisting of about 2 x 10(5) spheres per kg body weight. Tests for shunting of microspheres were performed and revealed shunt fractions in the systemic circulation of about 8%, with no significant shunting through the lungs. The microsphere method for determining cardiac output is thought to be an accurate method, suitable for small and medium sized animals."} {"id": "PMID:160610", "title": "Plasma lipids and lipoproteins in Down's syndrome.", "content": "Since mongoloids have been reported to differ from other patients with mental retardation by being virtually free of atheromatosis, we analysed plasma lipids and lipoproteins in twenty mongoloid and in twenty age-matched non-mongoloid mentally retarded patients living in the same institution. Plasma total cholesterol in the mongoloids did not differ significantly from that of the control group, but it was low in both groups in comparison with the Finnish population in general. Plasma total triglyceride concentration was higher (P less than 0.01) in the mongoloids than in the controls. This was reflected in higher VLDL-triglyceride and-cholesterol concentrations in the mongoloids. Plasma apolipoprotein B levels were higher (P less than 0.05) and the ratio of apolipoprotein A-1 to apolipoprotein B was lower (less than 0.05) in the mongoloids. The plasma lipid concentrations were in accordance with the significantly higher relative body weights in the mongoloid group. Blood pressure was slightly but significantly lower and cigarette smoking was less common in patients with Down's syndrome. Our results did not explain the reported lower frequency of atheromatosis in Down's syndrome.", "contents": "Plasma lipids and lipoproteins in Down's syndrome. Since mongoloids have been reported to differ from other patients with mental retardation by being virtually free of atheromatosis, we analysed plasma lipids and lipoproteins in twenty mongoloid and in twenty age-matched non-mongoloid mentally retarded patients living in the same institution. Plasma total cholesterol in the mongoloids did not differ significantly from that of the control group, but it was low in both groups in comparison with the Finnish population in general. Plasma total triglyceride concentration was higher (P less than 0.01) in the mongoloids than in the controls. This was reflected in higher VLDL-triglyceride and-cholesterol concentrations in the mongoloids. Plasma apolipoprotein B levels were higher (P less than 0.05) and the ratio of apolipoprotein A-1 to apolipoprotein B was lower (less than 0.05) in the mongoloids. The plasma lipid concentrations were in accordance with the significantly higher relative body weights in the mongoloid group. Blood pressure was slightly but significantly lower and cigarette smoking was less common in patients with Down's syndrome. Our results did not explain the reported lower frequency of atheromatosis in Down's syndrome."} {"id": "PMID:160612", "title": "Studies of anti-lymphocyte antibody of patients with active SLE. I. Cause of loss of suppressor T-lymphocyte function.", "content": "Effect of anti-lymphocyte antibody of active systemic lupus erythematosus (SLE) on lymphocyte function was examined. Lymphocytes from normal individuals treated with anti-lymphocyte antibody and complement exhibited marked inhibition of response to concanavalin A (Con A), while the response of lymphocytes to phytohaemagglutinin M (PHA-M) and pokeweed mitogen (PWM) was slightly affected. In mixed lymphocyte culture response, both stimulator and responder cells were insensitive to anti-lymphocyte antibody. Treatment of sensitized lymphocytes with anti-lymphocyte antibody and complement caused a dose-dependent suppression of blastogenic response to purified protein derivatives (PPD). No effect, however, was noted on migration-inhibitory factor (MIF)-producing cells. In PWM-driven Ig synthesis, T lymphocytes lacking the anti-lymphocyte antibody-reactive T-cell subset enhanced PWM-driven Ig synthesis of autologous B lymphocytes. Con-A-induced suppressor function of lymphocytes was abolished by the treatment with anti-lymphocyte antibody and complement. The present study demonstrated that lymphocytes from normal individuals after treatment with anti-lymphocyte antibody and complement showed similar immunological reactivities with lymphocytes from active SLE, indicating that those anti-lymphocyte antibodies could play an important role in defective suppressor cell function.", "contents": "Studies of anti-lymphocyte antibody of patients with active SLE. I. Cause of loss of suppressor T-lymphocyte function. Effect of anti-lymphocyte antibody of active systemic lupus erythematosus (SLE) on lymphocyte function was examined. Lymphocytes from normal individuals treated with anti-lymphocyte antibody and complement exhibited marked inhibition of response to concanavalin A (Con A), while the response of lymphocytes to phytohaemagglutinin M (PHA-M) and pokeweed mitogen (PWM) was slightly affected. In mixed lymphocyte culture response, both stimulator and responder cells were insensitive to anti-lymphocyte antibody. Treatment of sensitized lymphocytes with anti-lymphocyte antibody and complement caused a dose-dependent suppression of blastogenic response to purified protein derivatives (PPD). No effect, however, was noted on migration-inhibitory factor (MIF)-producing cells. In PWM-driven Ig synthesis, T lymphocytes lacking the anti-lymphocyte antibody-reactive T-cell subset enhanced PWM-driven Ig synthesis of autologous B lymphocytes. Con-A-induced suppressor function of lymphocytes was abolished by the treatment with anti-lymphocyte antibody and complement. The present study demonstrated that lymphocytes from normal individuals after treatment with anti-lymphocyte antibody and complement showed similar immunological reactivities with lymphocytes from active SLE, indicating that those anti-lymphocyte antibodies could play an important role in defective suppressor cell function."} {"id": "PMID:160613", "title": "Human T-lymphocyte subpopulations: alterations in systemic lupus erythematosus.", "content": "Sharply reduced proportions of T cells with Fc receptors for IgG (TG cells) were observed in blood samples from patients with systemic lupus erythematosus (SLE), mainly with active disease. This T-cell subset has previously been shown to be a suppressor in the pokeweed mitogen (PWM)-dependent B-cell differentiation. In contrast, the percentages of T cells with Fc receptors for IgM (TM cells), which have been shown to help immunoglobulin production, were not different from those of normals. TG cells present in the circulation of SLE patients were analysed for their functional capacities in antibody-dependent cell-mediated cytotoxicity and in the suppression of a PWM-induced B-cell differentiation. In both these assays TG cells from SLE patients had normal effector cell activity. This suggests that thr than a qualitative type.", "contents": "Human T-lymphocyte subpopulations: alterations in systemic lupus erythematosus. Sharply reduced proportions of T cells with Fc receptors for IgG (TG cells) were observed in blood samples from patients with systemic lupus erythematosus (SLE), mainly with active disease. This T-cell subset has previously been shown to be a suppressor in the pokeweed mitogen (PWM)-dependent B-cell differentiation. In contrast, the percentages of T cells with Fc receptors for IgM (TM cells), which have been shown to help immunoglobulin production, were not different from those of normals. TG cells present in the circulation of SLE patients were analysed for their functional capacities in antibody-dependent cell-mediated cytotoxicity and in the suppression of a PWM-induced B-cell differentiation. In both these assays TG cells from SLE patients had normal effector cell activity. This suggests that thr than a qualitative type."} {"id": "PMID:160614", "title": "Lymphocyte subpopulations in man: B-cell stimulation induced by pokeweed mitogen and irradiated T cells.", "content": "The enhanced stimulation of human B lymphocytes by pokeweed mitogen in the presence of irradiated T helper lymphocytes has been studied, revealing that the proliferative responses measured by incorporation of thymidine in cultures of B lymphocytes and irradiated T lymphocytes in a 1:2 or 1:4 ratio is mostly a function of the B cells. Only a minimal number, if any, of the T cells contaminating the B cell suspensions is stimulated to proliferation. This is in contrast to stimulation of the B-cell suspensions without addition of irradiated T cells, where both B cells and T cells proliferate. The irradiated T helper cells have no FcR for antigen-bound IgG, and as well allogeneic as autologous T cells exhibit helper capacity of equal strength. The test system described makes it possible selectively to test one B-cell function and the corresponding T helper capacity.", "contents": "Lymphocyte subpopulations in man: B-cell stimulation induced by pokeweed mitogen and irradiated T cells. The enhanced stimulation of human B lymphocytes by pokeweed mitogen in the presence of irradiated T helper lymphocytes has been studied, revealing that the proliferative responses measured by incorporation of thymidine in cultures of B lymphocytes and irradiated T lymphocytes in a 1:2 or 1:4 ratio is mostly a function of the B cells. Only a minimal number, if any, of the T cells contaminating the B cell suspensions is stimulated to proliferation. This is in contrast to stimulation of the B-cell suspensions without addition of irradiated T cells, where both B cells and T cells proliferate. The irradiated T helper cells have no FcR for antigen-bound IgG, and as well allogeneic as autologous T cells exhibit helper capacity of equal strength. The test system described makes it possible selectively to test one B-cell function and the corresponding T helper capacity."} {"id": "PMID:160615", "title": "Lymphocyte subpopulations in man: suppression of PWM-induced B-cell proliferation by infectious mononucleosis T cells.", "content": "The in vitro polyclonal pokeweed mitogen (PWM)-induced activation of human B lymphocytes is enhanced by addition of autologous or allogeneic irradiated T cells. This model for B/T-cell cooperation may be used to define and describe the balance between T helper and T suppressor phenomena. The present study investigates the helper and suppressor capacities of mononuclear cells isolated from peripheral blood of infectious mononucleosis patients during the acute disease and the reconvalescence period. During the acute disease we found a functional lack of T helper capacity; furthermore, the T cells were able to suppress the PWM and T-cell-dependent B-cell proliferation of healthy donor cells. The suppression was non-cytotoxic; i.e. not due to destruction of the responder cells. This phenomenon of non-cytotoxic suppression was found for all seven patients studied and disappeared during the reconvalescence period, indicating that the T lymphocytosis seen in infectious mononucleosis includes an expansion of T suppressor cells.", "contents": "Lymphocyte subpopulations in man: suppression of PWM-induced B-cell proliferation by infectious mononucleosis T cells. The in vitro polyclonal pokeweed mitogen (PWM)-induced activation of human B lymphocytes is enhanced by addition of autologous or allogeneic irradiated T cells. This model for B/T-cell cooperation may be used to define and describe the balance between T helper and T suppressor phenomena. The present study investigates the helper and suppressor capacities of mononuclear cells isolated from peripheral blood of infectious mononucleosis patients during the acute disease and the reconvalescence period. During the acute disease we found a functional lack of T helper capacity; furthermore, the T cells were able to suppress the PWM and T-cell-dependent B-cell proliferation of healthy donor cells. The suppression was non-cytotoxic; i.e. not due to destruction of the responder cells. This phenomenon of non-cytotoxic suppression was found for all seven patients studied and disappeared during the reconvalescence period, indicating that the T lymphocytosis seen in infectious mononucleosis includes an expansion of T suppressor cells."} {"id": "PMID:160616", "title": "Anaerobic, non-clostridial fasciitis and myonecrosis of the abdominal wall. Pure anaerobic infection originating from neglected inflammation of an urachal remnant.", "content": "A pure anaerobic infection of the abdominal wall of a 40-year-old man is described. The infection originated from an urachal remnant. Seven different bacterial strains were isolated. Even though no clostridia were involved, the infection caused extensive necrosis of the abdominal wall including both fascia and muscles.", "contents": "Anaerobic, non-clostridial fasciitis and myonecrosis of the abdominal wall. Pure anaerobic infection originating from neglected inflammation of an urachal remnant. A pure anaerobic infection of the abdominal wall of a 40-year-old man is described. The infection originated from an urachal remnant. Seven different bacterial strains were isolated. Even though no clostridia were involved, the infection caused extensive necrosis of the abdominal wall including both fascia and muscles."} {"id": "PMID:160624", "title": "A study of maternal participation in preschool programs for handicapped children and their families.", "content": "This study investigates the effects on maternal attitudes toward child-rearing of preschool programs for handicapped children and their families. Two types of programs were studied: programs emphasizing maternal participation and those minimizing maternal involvement. It was hypothesized that programs which stress mothers' involvement would result in more positive attitude changes than programs de-emphasizing maternal participation. The findings indicate that maternal involvement and program support are critical variables in promoting positive attitudes toward child-rearing. The authors recommend that a multi-regional study be undertaken to determine the applicability of this study's findings. Such information would be useful in future program development and in the training of program personnel.", "contents": "A study of maternal participation in preschool programs for handicapped children and their families. This study investigates the effects on maternal attitudes toward child-rearing of preschool programs for handicapped children and their families. Two types of programs were studied: programs emphasizing maternal participation and those minimizing maternal involvement. It was hypothesized that programs which stress mothers' involvement would result in more positive attitude changes than programs de-emphasizing maternal participation. The findings indicate that maternal involvement and program support are critical variables in promoting positive attitudes toward child-rearing. The authors recommend that a multi-regional study be undertaken to determine the applicability of this study's findings. Such information would be useful in future program development and in the training of program personnel."} {"id": "PMID:160625", "title": "Differences in maternal age-specific rates of Down syndrome between Jews of European origin and of North African or Asian origin.", "content": "Rates of Down syndrome in livebirths in West Jerusalem in 1964-1975 were studied in relation to the mother's continent of birth or, if she was born in Israel, to the maternal grandfather's continent of birth. In women of European origin the crude livebirth rate of Down syndrome was 1.3 per 1,000 livebirths. This crude rate and the maternal age-specific rates in this group were very close to those observed in a Swedish study and two studies of white livebirths in the United States. For West Jerusalem women of North African or Asian origin the crude rate was about 2.4 per 1,000 livebirths, and at all maternal ages except the youngest their rates were higher than for women of European origin. The summary adjusted relative risk for a Down syndrome livebirth for all those of North African or Asian origin, compared to those for women of European origin, was about 1.56. If attention is restricted to mothers born outside of Israel, the adjusted relative risk for mothers born in Europe, the Americas or English speaking countries of the British commonwealth compared to those born in North Africa or Asia was 1.97, consistent with a two-fold difference in the likelihood of a Down syndrome livebirth between thes two groups. To our knowledge this is the first report of ethnic differences in maternal age specific rates of Down syndrome that cannot be plausibly explained by differences in ascertainment.", "contents": "Differences in maternal age-specific rates of Down syndrome between Jews of European origin and of North African or Asian origin. Rates of Down syndrome in livebirths in West Jerusalem in 1964-1975 were studied in relation to the mother's continent of birth or, if she was born in Israel, to the maternal grandfather's continent of birth. In women of European origin the crude livebirth rate of Down syndrome was 1.3 per 1,000 livebirths. This crude rate and the maternal age-specific rates in this group were very close to those observed in a Swedish study and two studies of white livebirths in the United States. For West Jerusalem women of North African or Asian origin the crude rate was about 2.4 per 1,000 livebirths, and at all maternal ages except the youngest their rates were higher than for women of European origin. The summary adjusted relative risk for a Down syndrome livebirth for all those of North African or Asian origin, compared to those for women of European origin, was about 1.56. If attention is restricted to mothers born outside of Israel, the adjusted relative risk for mothers born in Europe, the Americas or English speaking countries of the British commonwealth compared to those born in North Africa or Asia was 1.97, consistent with a two-fold difference in the likelihood of a Down syndrome livebirth between thes two groups. To our knowledge this is the first report of ethnic differences in maternal age specific rates of Down syndrome that cannot be plausibly explained by differences in ascertainment."} {"id": "PMID:160630", "title": "HLA-D typing with lymphoblastoid cell lines. VII. A computer program for data analysis.", "content": "When lymphoblastoid cell lines (LCL) are substituted for peripheral blood lymphocytes from human typing cell donors in HLA-D typing experiments, a data analysis program must be designed to distinguish the effect of allo-reactivity from those peculiar to LCL, mainly the \"autologous-stimulation\" effect. The computer program described in this report was created specifically for such an analysis. The rationale for the design of this program is presented in the preceding report (see this issue).", "contents": "HLA-D typing with lymphoblastoid cell lines. VII. A computer program for data analysis. When lymphoblastoid cell lines (LCL) are substituted for peripheral blood lymphocytes from human typing cell donors in HLA-D typing experiments, a data analysis program must be designed to distinguish the effect of allo-reactivity from those peculiar to LCL, mainly the \"autologous-stimulation\" effect. The computer program described in this report was created specifically for such an analysis. The rationale for the design of this program is presented in the preceding report (see this issue)."} {"id": "PMID:160631", "title": "A micromethod for prospectively testing lymphocyte-mediated cytotoxicity (LMC) using fresh or frozen cells labelled with a fluorescent dye.", "content": "A direct, specific and rapid method has been developed to prospectively evaluate lymphocyte mediated cytotoxicity (LMC) for kidney transplant recipients. Donor lymphocytes, labeled with fluorescein diacetate, were incubated in a microtest plate for 2 h with recipients' effector cells. The percentage of fluorescent cells in each well was estimated relative to controls using an inverted phase fluorescence microscope. Lymphocytes obtained from seven of 12 recipients post-transplantation exhibited positive reactions, fluorescence of labeled donor cells was reduced to 30-65% of that observed in controls, and these reactive patients required nephrectomies. The responses of the remaining five patients were negative. Tests with their donor cells showed 80-95% control fluorescence, with favorable transplant results. Six of 21 recipients evaluated prospectively required nephrectomies within 34 days post-transplantation. Three of these subjects showed 15-65% control fluorescence, a positive LMC response; the other three yielded negative LMC responses but required nephrectomies possibly due to renal ischemia prior to transplantation. The remaining 15 patients demonstrated 85-90% control fluorescence with graft function continuing for 17 to 270 days. The results from direct LMC tests with a fluorescent label indicate that the system is of value in predicting early rejection of renal allotransplants.", "contents": "A micromethod for prospectively testing lymphocyte-mediated cytotoxicity (LMC) using fresh or frozen cells labelled with a fluorescent dye. A direct, specific and rapid method has been developed to prospectively evaluate lymphocyte mediated cytotoxicity (LMC) for kidney transplant recipients. Donor lymphocytes, labeled with fluorescein diacetate, were incubated in a microtest plate for 2 h with recipients' effector cells. The percentage of fluorescent cells in each well was estimated relative to controls using an inverted phase fluorescence microscope. Lymphocytes obtained from seven of 12 recipients post-transplantation exhibited positive reactions, fluorescence of labeled donor cells was reduced to 30-65% of that observed in controls, and these reactive patients required nephrectomies. The responses of the remaining five patients were negative. Tests with their donor cells showed 80-95% control fluorescence, with favorable transplant results. Six of 21 recipients evaluated prospectively required nephrectomies within 34 days post-transplantation. Three of these subjects showed 15-65% control fluorescence, a positive LMC response; the other three yielded negative LMC responses but required nephrectomies possibly due to renal ischemia prior to transplantation. The remaining 15 patients demonstrated 85-90% control fluorescence with graft function continuing for 17 to 270 days. The results from direct LMC tests with a fluorescent label indicate that the system is of value in predicting early rejection of renal allotransplants."} {"id": "PMID:160632", "title": "Effect of chronic administration of aldosterone on bile secretion, on liver cytochrome P-450, and on red blood cell sodium content.", "content": "Male adult albino rabbits received, during a period of two weeks, a daily subcutaneous injection of aldosterone, 150 micrograms/kg body weight. Twenty-four hr after the last injection, bile was collected during two hr under anaestheia, then the liver was removed and submitted to cytochrome P-450 measurements and microscopic analyses. Red blood cell sodium content was measured before and after aldosterone treatment. In animals treated with aldosterone, compared with controls, we found: (1) a significant diminution (p less than 0.01) of bile flow rate, of sodium biliary excretion and of biliary bile acid output; (2) a significant increase (p less than 0.001) of liver cytochrome P-450; (3) hyaline modifications of hepatocytes without necrosis or steatosis; (4) a proliferation of liver smooth endoplasmic reticulum; (5) an increase (p less than 0.001) of red blood cell sodium content.", "contents": "Effect of chronic administration of aldosterone on bile secretion, on liver cytochrome P-450, and on red blood cell sodium content. Male adult albino rabbits received, during a period of two weeks, a daily subcutaneous injection of aldosterone, 150 micrograms/kg body weight. Twenty-four hr after the last injection, bile was collected during two hr under anaestheia, then the liver was removed and submitted to cytochrome P-450 measurements and microscopic analyses. Red blood cell sodium content was measured before and after aldosterone treatment. In animals treated with aldosterone, compared with controls, we found: (1) a significant diminution (p less than 0.01) of bile flow rate, of sodium biliary excretion and of biliary bile acid output; (2) a significant increase (p less than 0.001) of liver cytochrome P-450; (3) hyaline modifications of hepatocytes without necrosis or steatosis; (4) a proliferation of liver smooth endoplasmic reticulum; (5) an increase (p less than 0.001) of red blood cell sodium content."} {"id": "PMID:160633", "title": "Carbohydrate metabolism in Down's syndrome.", "content": "Carbohydrate metabolism was studied in eight patients with Down's syndrome, aged 8 to 18 years. Diabetic glucose tolerance was observed in only one patient with obesity. This impaired glucose tolerance was improved with the weight reduction due to diet restriction. The flat glucose tolerance curves with low peak values were also observed in the other two patients. In the remaining five patients, normal glucose tolerance was obtained. Insulin response and free fatty acid levels during oral glucose load were not characteristic except for the diabetic patient with obesity. The sera of Down's syndrome showed normal binding capacity for insulin. These results suggest that obesity might partly participate in the impaired glucose tolerance in Down's syndrome.", "contents": "Carbohydrate metabolism in Down's syndrome. Carbohydrate metabolism was studied in eight patients with Down's syndrome, aged 8 to 18 years. Diabetic glucose tolerance was observed in only one patient with obesity. This impaired glucose tolerance was improved with the weight reduction due to diet restriction. The flat glucose tolerance curves with low peak values were also observed in the other two patients. In the remaining five patients, normal glucose tolerance was obtained. Insulin response and free fatty acid levels during oral glucose load were not characteristic except for the diabetic patient with obesity. The sera of Down's syndrome showed normal binding capacity for insulin. These results suggest that obesity might partly participate in the impaired glucose tolerance in Down's syndrome."} {"id": "PMID:160634", "title": "Adsorption of suppressor cell activity on mouse macrophage monolayers.", "content": "Suppressor cell activity is high in the spleen of C57BL/6 mice sensitized to the allogeneic P-815 mastocytoma. The suppressor cells inhibit proliferation of normal mouse spleen cells in mixed lymphocyte cultures. Preincubation of tumor-allosensitized spleen cells on monolayers of syngeneic or allogeneic macrophages reduces suppressor activity. Preincubation on monolayers of spleen cells does not affect suppressor activity. Suppressor cells can be retrieved from the macrophage monolayers used for adsorption. Heat-killed macrophages fail to adsorb out suppressor cell activity. Incubation of tumor-allosensitized spleen cells on syngeneic macrophage monolayers does not reduce cytotoxic cell activity. Removal of suppressor cell activity by macrophage adsorption restores helper activity of tumor-allosensitized spleen cells. These results demonstrate that suppressor cell activity can be reduced by contact with macrophages and point to an additional role for the macrophage in regulating the immune response to tumors.", "contents": "Adsorption of suppressor cell activity on mouse macrophage monolayers. Suppressor cell activity is high in the spleen of C57BL/6 mice sensitized to the allogeneic P-815 mastocytoma. The suppressor cells inhibit proliferation of normal mouse spleen cells in mixed lymphocyte cultures. Preincubation of tumor-allosensitized spleen cells on monolayers of syngeneic or allogeneic macrophages reduces suppressor activity. Preincubation on monolayers of spleen cells does not affect suppressor activity. Suppressor cells can be retrieved from the macrophage monolayers used for adsorption. Heat-killed macrophages fail to adsorb out suppressor cell activity. Incubation of tumor-allosensitized spleen cells on syngeneic macrophage monolayers does not reduce cytotoxic cell activity. Removal of suppressor cell activity by macrophage adsorption restores helper activity of tumor-allosensitized spleen cells. These results demonstrate that suppressor cell activity can be reduced by contact with macrophages and point to an additional role for the macrophage in regulating the immune response to tumors."} {"id": "PMID:160636", "title": "Suppressor cells in specific unresponsiveness to skin allografts in thymectomized, ALS-treated, marrow-injected mice.", "content": "Spleen cells from thymectomized antilymphocyte serum (ALS)-treated B6AF1 mice bearing enhanced C3H/He grafts after the infection of C3H/He marrow were assayed for their ability to suppress the response to C3H/He grafts after transfer to syngeneic B6AF1 recipients. Cells were transferred from thymectomized ALS-treated B6AF1 mice that had received either a C3H/He graft alone, C3H/He marrow alone, or both a graft and marrow. Cells were removed from donors and transferred at either day +13, +42, +62, +100, or +150. Spleen cells from thymectomized mice were unable to transfer unresponsiveness regardless of donor treatment or time of transfer.", "contents": "Suppressor cells in specific unresponsiveness to skin allografts in thymectomized, ALS-treated, marrow-injected mice. Spleen cells from thymectomized antilymphocyte serum (ALS)-treated B6AF1 mice bearing enhanced C3H/He grafts after the infection of C3H/He marrow were assayed for their ability to suppress the response to C3H/He grafts after transfer to syngeneic B6AF1 recipients. Cells were transferred from thymectomized ALS-treated B6AF1 mice that had received either a C3H/He graft alone, C3H/He marrow alone, or both a graft and marrow. Cells were removed from donors and transferred at either day +13, +42, +62, +100, or +150. Spleen cells from thymectomized mice were unable to transfer unresponsiveness regardless of donor treatment or time of transfer."} {"id": "PMID:160638", "title": "Association of interstitial pneumonia and diminished in vitro lymphocyte blastogenesis in human marrow graft recipients.", "content": "The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP.", "contents": "Association of interstitial pneumonia and diminished in vitro lymphocyte blastogenesis in human marrow graft recipients. The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP."} {"id": "PMID:160645", "title": "Thrombogenic potential of dacron grafts after prior exposure to whole blood, plasma, or albumin.", "content": "On hundred forty six (146) vascular graft insertions have been examined to determine the best exposure media, the mode of exposure, and the time of exposure required to change the TP of knitted dacron fabric. Whole blood, plasma, albumin, and Ringer's lactate (as control) were the media used. The mode of exposure was by either simple soaking or physiological perfusion with the appropriate media. The time of exposure was from one hour to 7 days. Simple soaking in species-specific albumin was found to be highly effective in lowering the TP of knitted dacron and we advocate this as the initial step in preclotting dacron grafts. This step is equally critical in the smaller vascular replacements and should lead to improved patency of these dacron vascular grafts.", "contents": "Thrombogenic potential of dacron grafts after prior exposure to whole blood, plasma, or albumin. On hundred forty six (146) vascular graft insertions have been examined to determine the best exposure media, the mode of exposure, and the time of exposure required to change the TP of knitted dacron fabric. Whole blood, plasma, albumin, and Ringer's lactate (as control) were the media used. The mode of exposure was by either simple soaking or physiological perfusion with the appropriate media. The time of exposure was from one hour to 7 days. Simple soaking in species-specific albumin was found to be highly effective in lowering the TP of knitted dacron and we advocate this as the initial step in preclotting dacron grafts. This step is equally critical in the smaller vascular replacements and should lead to improved patency of these dacron vascular grafts."} {"id": "PMID:160647", "title": "Ureteral replacement with a new prosthesis.", "content": "A new flexible silicone ureteral prosthesis has been developed and implanted by a new technique in 20 miniature pigs. The improved implantation technique and the results are described. All prostheses remained firmly attached in their position and drained the upper urine collecting system adequately during an observation period up to 12 mos. Leakage, incrustation, dislocation or rejection did not occur. The promising results encouraged us to continue our investigations to get long term experience for clinical trial in human patients for whom nephrostomy is the alternative.", "contents": "Ureteral replacement with a new prosthesis. A new flexible silicone ureteral prosthesis has been developed and implanted by a new technique in 20 miniature pigs. The improved implantation technique and the results are described. All prostheses remained firmly attached in their position and drained the upper urine collecting system adequately during an observation period up to 12 mos. Leakage, incrustation, dislocation or rejection did not occur. The promising results encouraged us to continue our investigations to get long term experience for clinical trial in human patients for whom nephrostomy is the alternative."} {"id": "PMID:160648", "title": "[Pathogenesis of acute osteomyelitis].", "content": "Pathogenesis of acute osteomyelitis is analyzed from the standpoint of disorders in the bone microcirculation. It is stated that in acute osteomyelitis there occur some disorders in microcirculation due to extravascular compression and intravascular occlusion of the bone vessels. The analysis of pathogenesis of acute osteomyelitis from the standpoint of disorders in the microcirculation of the osseous tissue is believed to be expedient for the correct understanding of pathological processes occurring in the bone, and for purposeful pathogenetic therapy.", "contents": "[Pathogenesis of acute osteomyelitis]. Pathogenesis of acute osteomyelitis is analyzed from the standpoint of disorders in the bone microcirculation. It is stated that in acute osteomyelitis there occur some disorders in microcirculation due to extravascular compression and intravascular occlusion of the bone vessels. The analysis of pathogenesis of acute osteomyelitis from the standpoint of disorders in the microcirculation of the osseous tissue is believed to be expedient for the correct understanding of pathological processes occurring in the bone, and for purposeful pathogenetic therapy."} {"id": "PMID:160649", "title": "[Recurrent right-ventricular hypertrophy in patients with congenital isolated stenosis of the pulmonary artery and outlet tract of the right ventricle in the immediate and late periods after surgery].", "content": "The degree of hypertrophy of the right ventricle is proportionate to the size of the systolic pressure gradient between the right ventricle and pulmonary artery prior to operation. The involution of hypertrophy is dependent on the type of stenosis, age of the patient and the term of surgery.", "contents": "[Recurrent right-ventricular hypertrophy in patients with congenital isolated stenosis of the pulmonary artery and outlet tract of the right ventricle in the immediate and late periods after surgery]. The degree of hypertrophy of the right ventricle is proportionate to the size of the systolic pressure gradient between the right ventricle and pulmonary artery prior to operation. The involution of hypertrophy is dependent on the type of stenosis, age of the patient and the term of surgery."} {"id": "PMID:160650", "title": "[4-stage system of treatment of patients with injuries of the musculo-skeletal apparatus].", "content": "The four-step system for the treatment of traumatological patients contributes to earlier rehabilitation and shortens the time fo staying in hospitals. It also decreases the invalidism percentage.", "contents": "[4-stage system of treatment of patients with injuries of the musculo-skeletal apparatus]. The four-step system for the treatment of traumatological patients contributes to earlier rehabilitation and shortens the time fo staying in hospitals. It also decreases the invalidism percentage."} {"id": "PMID:160651", "title": "[Diagnosis and treatment of primary malignant thyroid tumors in an endemic focus].", "content": "In authors' opinion an inadequate knowledge of the clinical course and disparagement of the role of puncture and operation biopsies constitute the causes of hypodiagnosis of primary malignant tumors. An exceptional use of repeated operations in case of \"histologic discoveries\" of the tumors together with underestimation of radialogic and hormonal treatment should be considered as therapeutic errors.", "contents": "[Diagnosis and treatment of primary malignant thyroid tumors in an endemic focus]. In authors' opinion an inadequate knowledge of the clinical course and disparagement of the role of puncture and operation biopsies constitute the causes of hypodiagnosis of primary malignant tumors. An exceptional use of repeated operations in case of \"histologic discoveries\" of the tumors together with underestimation of radialogic and hormonal treatment should be considered as therapeutic errors."} {"id": "PMID:160658", "title": "Erythrophagocytosis by the sinus endothelial cell of the spleen in haemolytic anaemias.", "content": "An ultrastructural study of spleens from patients with a heterogeneous group of haemolytic anaemias was undertaken in order to determine whether sinus endothelial cells have erythrophagocytic ability. In most cases, sinus endothelial cells contained erythrocytes and various stages of intracellular degradation of engulfed erythrocytes were noted. Though the frequency of erythrophagocytosis varied from case to case, phagocytosis of erythrocytes by the endothelial cell was more frequent in cases in which cordal macrophages showed active erythrophagocytosis. These results suggest that the sinus endothelial cells have erythropagocytic ability in certain pathological states, especially when the demands for the removal of defective erythrocytes are increased. However, the bulk of erythrophagocytosis is carried out by cordal macrophages, and endothelial phagocytosis has a minor significance in the developemnt of haemolytic anaemia. Two possible processes by which erythrocytes come into contact with sinus endothelial cells are suggested.", "contents": "Erythrophagocytosis by the sinus endothelial cell of the spleen in haemolytic anaemias. An ultrastructural study of spleens from patients with a heterogeneous group of haemolytic anaemias was undertaken in order to determine whether sinus endothelial cells have erythrophagocytic ability. In most cases, sinus endothelial cells contained erythrocytes and various stages of intracellular degradation of engulfed erythrocytes were noted. Though the frequency of erythrophagocytosis varied from case to case, phagocytosis of erythrocytes by the endothelial cell was more frequent in cases in which cordal macrophages showed active erythrophagocytosis. These results suggest that the sinus endothelial cells have erythropagocytic ability in certain pathological states, especially when the demands for the removal of defective erythrocytes are increased. However, the bulk of erythrophagocytosis is carried out by cordal macrophages, and endothelial phagocytosis has a minor significance in the developemnt of haemolytic anaemia. Two possible processes by which erythrocytes come into contact with sinus endothelial cells are suggested."} {"id": "PMID:160657", "title": "Early (stage A) prostatic cancer. IV. Methodological criteria for histopathological diagnosis.", "content": "This study was performed in order to elucidate some of the problems of incidence, morphology and natural history concerned with Stage A prostatic cancer or prostatic microcarcinoma (PMC). The prostates of 100 patients, treated by subtotal prostatectomy for benign prostatic hyperplasia (BPH), were studied by comparing both routine and step-section techniques. The incidence of PMC was 41% by the former and 86% by the latter technique. Assessment of the size of PMC, as measured by the sum of the two main diameters, resulted in three groups: A1, A2, A3. The last of these may represent a frankly malignant condition, judged by size and the histological appearance. Radical prostatectomy is strongly suggested as appropriate therapy for this group.", "contents": "Early (stage A) prostatic cancer. IV. Methodological criteria for histopathological diagnosis. This study was performed in order to elucidate some of the problems of incidence, morphology and natural history concerned with Stage A prostatic cancer or prostatic microcarcinoma (PMC). The prostates of 100 patients, treated by subtotal prostatectomy for benign prostatic hyperplasia (BPH), were studied by comparing both routine and step-section techniques. The incidence of PMC was 41% by the former and 86% by the latter technique. Assessment of the size of PMC, as measured by the sum of the two main diameters, resulted in three groups: A1, A2, A3. The last of these may represent a frankly malignant condition, judged by size and the histological appearance. Radical prostatectomy is strongly suggested as appropriate therapy for this group."} {"id": "PMID:160659", "title": "Correlation of vertebral malformations with the synthesis and content of mucopolysaccharides during chondrogenesis.", "content": "Treating mice of strain C57BL/6Ffm on day 9 of gestation with 10 mg/kg of 5-fluoro-2'-deoxycytidine (FCdR) resulted in malformations of the thoracic vertebral column (ThVC) in 98% of near-term fetuses (Degenhardt et al., 1968). The spectrum of malformations was broad: fusion, dysplasia, cleft, aplasia and hypoplasia were all produced. Fusions of two or more segments represented more than half of all malformations (Bosse, 1978). The alterations in embryonic precartilage and cartilage after FCdR-treatment were followed from day 11 to day 15 in a biochemical and histological study. Biochemically, the 35S-uptake into embryonic mucopolysaccharides (MPS) and the content of total MPS and seven fractions of MPS in embryos or isolated ThVCs were analyzed. The histological variables studied were the types and incidence of malformations of the ThVC, 35S-autoradiography of the ThVC, and the amount of alcian blue-stained cartilaginous matrix. The results showed that on day 11 the synthesis of embryonic MPS was not affected, on day 12 the synthesis of MPS was greatly reduced, on day 13 the synthesis of MPS was slightly reduced while the MPS-content was not affected. On day 13 aplasias were seen in the same percentage as at term, but no fusions were detected. By day 14 the MPS-content was greatly reduced; hyaluronate, condroitin 4-sulfate, and chondroitin 6-sulfate being principally involved; the first fusions were seen. On day 15 the MPS-content was slightly reduced (chondroitin 6-sulfate and heparan sulfate were involved), fusions were complete. The results are discussed in terms of disturbance of structure and function of the notochord and intervertebral discs with the production of fusions, the main type of vertebral malformation in these experiments.", "contents": "Correlation of vertebral malformations with the synthesis and content of mucopolysaccharides during chondrogenesis. Treating mice of strain C57BL/6Ffm on day 9 of gestation with 10 mg/kg of 5-fluoro-2'-deoxycytidine (FCdR) resulted in malformations of the thoracic vertebral column (ThVC) in 98% of near-term fetuses (Degenhardt et al., 1968). The spectrum of malformations was broad: fusion, dysplasia, cleft, aplasia and hypoplasia were all produced. Fusions of two or more segments represented more than half of all malformations (Bosse, 1978). The alterations in embryonic precartilage and cartilage after FCdR-treatment were followed from day 11 to day 15 in a biochemical and histological study. Biochemically, the 35S-uptake into embryonic mucopolysaccharides (MPS) and the content of total MPS and seven fractions of MPS in embryos or isolated ThVCs were analyzed. The histological variables studied were the types and incidence of malformations of the ThVC, 35S-autoradiography of the ThVC, and the amount of alcian blue-stained cartilaginous matrix. The results showed that on day 11 the synthesis of embryonic MPS was not affected, on day 12 the synthesis of MPS was greatly reduced, on day 13 the synthesis of MPS was slightly reduced while the MPS-content was not affected. On day 13 aplasias were seen in the same percentage as at term, but no fusions were detected. By day 14 the MPS-content was greatly reduced; hyaluronate, condroitin 4-sulfate, and chondroitin 6-sulfate being principally involved; the first fusions were seen. On day 15 the MPS-content was slightly reduced (chondroitin 6-sulfate and heparan sulfate were involved), fusions were complete. The results are discussed in terms of disturbance of structure and function of the notochord and intervertebral discs with the production of fusions, the main type of vertebral malformation in these experiments."} {"id": "PMID:160660", "title": "Emiocytotic granule release without intraluminal stimulus in human colonic endocrine cells of fetuses, children and adults.", "content": "In endocrine cells of the colon of adults, children and fetuses, exocytotic granule release without any specific stimulation is reported. Omega-invaginations are observed on both the lateral and basal surfaces of all types of colonic endocrine cells. Several explanations for the phenomenon are suggested: 1) emiocytosis is probably more frequent in the colon than in the proximal gut, this allows its observation without requiring an exogenous stimulus, 2) since most of the exocytotic figures are from anaesthetized subjects it is also assumed that contraction of the muscular layer induced by anaesthetics and the resulting increase in intraluminal pressure were the possible causes of granule release, 3) in non-anaesthetized subjects release may have taken place in response to a normal endogenous physiological stimulus, or to the dilation of colon during colonoscopy. Certain figures on lateral surfaces between endocrine and adjacent cells i.e., bulges of parallel plasma membranes surrounding a secretory granule, were observed. Their significance is unknown.", "contents": "Emiocytotic granule release without intraluminal stimulus in human colonic endocrine cells of fetuses, children and adults. In endocrine cells of the colon of adults, children and fetuses, exocytotic granule release without any specific stimulation is reported. Omega-invaginations are observed on both the lateral and basal surfaces of all types of colonic endocrine cells. Several explanations for the phenomenon are suggested: 1) emiocytosis is probably more frequent in the colon than in the proximal gut, this allows its observation without requiring an exogenous stimulus, 2) since most of the exocytotic figures are from anaesthetized subjects it is also assumed that contraction of the muscular layer induced by anaesthetics and the resulting increase in intraluminal pressure were the possible causes of granule release, 3) in non-anaesthetized subjects release may have taken place in response to a normal endogenous physiological stimulus, or to the dilation of colon during colonoscopy. Certain figures on lateral surfaces between endocrine and adjacent cells i.e., bulges of parallel plasma membranes surrounding a secretory granule, were observed. Their significance is unknown."} {"id": "PMID:160661", "title": "Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus.", "content": "Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.", "contents": "Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus. Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus."} {"id": "PMID:160662", "title": "Lymphoepitheloid cell malignant lymphoma (Lennert).", "content": "Typical epitheloid cell formations were found in 175 of 500 cases of various types of Hodgkin's disease. No distinctive behaviour was found in cases with epitheloid structures. Close attention has been devoted to a further series of 23 lymphoepitheloid cell malignant lymphomata marked by focal nuclear atypicality in their epitheloid cell granulomas, which destroyed the basic neoplastic structure of the lymph node in many cases, necessitating further biopsy. In this series not only Hodgkin's disease (7 cases) but also some malignant lymphomas of non Hodgkin's types (3 x immunoblastoma, 3 x immunocytoma and 2 x T-lymphoblastoma) were found. In 6 cases only a tentative diagnosis of lymphoepitheloid cell malignant lymphoma could be made. The epitheloid granulomatous reaction tended to disappear gradually in all cases by repeated check-ups, and was apparently a secondary phenomenon. The cause of the epitheloid cell atypia was not evident although it proved to be an important diagnostic feature identifying an independent form of lymphoepitheloid malignant lymphoma. The subsequent development of this lesion suggested a mildly pleiomorphic highly malignant lymphoma, which might be of B cell origin, but sometimes demonstrably of the T cell series.", "contents": "Lymphoepitheloid cell malignant lymphoma (Lennert). Typical epitheloid cell formations were found in 175 of 500 cases of various types of Hodgkin's disease. No distinctive behaviour was found in cases with epitheloid structures. Close attention has been devoted to a further series of 23 lymphoepitheloid cell malignant lymphomata marked by focal nuclear atypicality in their epitheloid cell granulomas, which destroyed the basic neoplastic structure of the lymph node in many cases, necessitating further biopsy. In this series not only Hodgkin's disease (7 cases) but also some malignant lymphomas of non Hodgkin's types (3 x immunoblastoma, 3 x immunocytoma and 2 x T-lymphoblastoma) were found. In 6 cases only a tentative diagnosis of lymphoepitheloid cell malignant lymphoma could be made. The epitheloid granulomatous reaction tended to disappear gradually in all cases by repeated check-ups, and was apparently a secondary phenomenon. The cause of the epitheloid cell atypia was not evident although it proved to be an important diagnostic feature identifying an independent form of lymphoepitheloid malignant lymphoma. The subsequent development of this lesion suggested a mildly pleiomorphic highly malignant lymphoma, which might be of B cell origin, but sometimes demonstrably of the T cell series."} {"id": "PMID:160663", "title": "Alveolitis due to hair-spray. Ultrastructural observations in two patients and the results of experimental investigations.", "content": "Observation of two patients with hair-spray induced lung disease have prompted us to study the ultrastructure of the lung lesion. We have compared the results with experimental lesions in animals injected with hair-spray extracts and with human monocyte cell cultures exposed to hair-spray. The lungs show a chronic alveolitis with a striking granulomatous reaction including macrophages and multinucleated giant cells of the foreign body type. The intraalveolar and interstitial macrophages and the giant cells all contain PAS-positive material. Ultrastructurally distinct lamellar inclusions are found in the secondary lysosomes of the macrophages and giant cells. Identical structures can be produced in animals injected with hair-spray extracts and with polyvinyl-pyrrolidone and -acetate (PVP/PVA), which are regular ingredients of hair-sprays. Large, presumeably polymeric particles (PVP/PVA) are ingested by giant cells. This \"gigantophagocytosis\" is associated with the fusion of mononuclear phagocytes and leads to the genesis of giant cells. In cell cultures of human blood monocytes hair-spray extracts and PVP/PVA induce maturation and aggregation of these cells, with PAS-positive cytoplasmatic inclusions. The development of multinuclear giant cells in these monocyte cell cultures is also seen. These observations suggest that hair-spray induced lung disease is caused by the prolonged and extensive body response of the local mononuclear phagocyte system (MPS). Overstimulation of the MPS leads to a quantitative and qualitative change which is followed by a partial blockade of this system. The alveolitis is a consequence of the foreign body response to inhaled hair-spray substances.", "contents": "Alveolitis due to hair-spray. Ultrastructural observations in two patients and the results of experimental investigations. Observation of two patients with hair-spray induced lung disease have prompted us to study the ultrastructure of the lung lesion. We have compared the results with experimental lesions in animals injected with hair-spray extracts and with human monocyte cell cultures exposed to hair-spray. The lungs show a chronic alveolitis with a striking granulomatous reaction including macrophages and multinucleated giant cells of the foreign body type. The intraalveolar and interstitial macrophages and the giant cells all contain PAS-positive material. Ultrastructurally distinct lamellar inclusions are found in the secondary lysosomes of the macrophages and giant cells. Identical structures can be produced in animals injected with hair-spray extracts and with polyvinyl-pyrrolidone and -acetate (PVP/PVA), which are regular ingredients of hair-sprays. Large, presumeably polymeric particles (PVP/PVA) are ingested by giant cells. This \"gigantophagocytosis\" is associated with the fusion of mononuclear phagocytes and leads to the genesis of giant cells. In cell cultures of human blood monocytes hair-spray extracts and PVP/PVA induce maturation and aggregation of these cells, with PAS-positive cytoplasmatic inclusions. The development of multinuclear giant cells in these monocyte cell cultures is also seen. These observations suggest that hair-spray induced lung disease is caused by the prolonged and extensive body response of the local mononuclear phagocyte system (MPS). Overstimulation of the MPS leads to a quantitative and qualitative change which is followed by a partial blockade of this system. The alveolitis is a consequence of the foreign body response to inhaled hair-spray substances."} {"id": "PMID:160664", "title": "Liquid paraffin pneumonia--with chemical analysis and electronmicroscopy.", "content": "Liquid paraffin pneumonia was diagnosed after open lung biopsy in a woman age 73 with a hiatus hernia and rheumatoid arthritis who had been taking liquid paraffin nightly for fifty two years. Histological examination showed a lipid type pneumonia with involvement of alveoli, interstitial tissues and brochioles. Chemical analysis of the lung showed total lipids of 17.7% (w/w), 86% was liquid paraffin which was positively identified by infrared spectroscopy. Transmission electronmicroscopy showed macrophages in the alveoli filled by phagosomes. The alveoli were mainly lined by alveolar type II cells. Scanning electronmicroscopy showed alveoli filled by a mass of vacuoled material.", "contents": "Liquid paraffin pneumonia--with chemical analysis and electronmicroscopy. Liquid paraffin pneumonia was diagnosed after open lung biopsy in a woman age 73 with a hiatus hernia and rheumatoid arthritis who had been taking liquid paraffin nightly for fifty two years. Histological examination showed a lipid type pneumonia with involvement of alveoli, interstitial tissues and brochioles. Chemical analysis of the lung showed total lipids of 17.7% (w/w), 86% was liquid paraffin which was positively identified by infrared spectroscopy. Transmission electronmicroscopy showed macrophages in the alveoli filled by phagosomes. The alveoli were mainly lined by alveolar type II cells. Scanning electronmicroscopy showed alveoli filled by a mass of vacuoled material."} {"id": "PMID:160665", "title": "Fatal eosinophilic gastroenterocolitis in a two-year-old child.", "content": "We report a case of eosinophilic gastroenterocolitis in a 2-year-old child with extensive fibrosis, atrophy of the muscularis propria and involvement of stomach, small bowel and colon. Following an attack of acute gastroenteritis at the age of 15 months the symptoms of ileus persisted. A biopsy of small bowel at the age of 18 months showed numerous eosinophilic granulocytes in the mucosa. At the age of 28 months the child died with paralytic ileus. This is the first case known to us of an eosinophilic gastroenteritis in early childhood with a fatal outcome.", "contents": "Fatal eosinophilic gastroenterocolitis in a two-year-old child. We report a case of eosinophilic gastroenterocolitis in a 2-year-old child with extensive fibrosis, atrophy of the muscularis propria and involvement of stomach, small bowel and colon. Following an attack of acute gastroenteritis at the age of 15 months the symptoms of ileus persisted. A biopsy of small bowel at the age of 18 months showed numerous eosinophilic granulocytes in the mucosa. At the age of 28 months the child died with paralytic ileus. This is the first case known to us of an eosinophilic gastroenteritis in early childhood with a fatal outcome."} {"id": "PMID:160666", "title": "Colorectal polyposis with mixed juvenile and adenomatous patterns.", "content": "An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up.", "contents": "Colorectal polyposis with mixed juvenile and adenomatous patterns. An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up."} {"id": "PMID:160680", "title": "[Laparoscopic picture and a working laparoscopic classification of chronic perihepatitis].", "content": "The author established chronic perihepatitis, via laparoscopy, in 61.6 percent of the investigated 350 patients in the course of 12 years. Describing the most characteristic mascoscopic varieties of chronic perihepatitis, the author groups them in seven separate form: I. Perihepatitis diffusa, corresponding to Zuckergussleber of Curschmann. II. Perihepatitis adhesiva and III. Perihepatitis circumscripta. The latter, on its part is subdivided to 5 separate forms of chronic perihepatitis: 1. Perihepatitis arachnoidealis, 2. Perihepatitis marginalis, 3. Perihepatitis areata et striata, 4. Perihepatitis miliaris disseminata, 5. Perihepatitis paravesicalis. That working laparoscopic classification contributes to the precise diagnostics and to the clinical interpretation of the separate forms of chronic perihepatitis. With the aid of lapraoscope the author performed a partial decapsulation of diffuse perihepatitis in 12 patients, without complications observed. Diffuse perihepatitis is, for the first time, described in patients with chronic hepatitis, in a patient with multiple liver abscesses and in one female-patient with peritoneal carcinosis and hemorrhagic ascites.", "contents": "[Laparoscopic picture and a working laparoscopic classification of chronic perihepatitis]. The author established chronic perihepatitis, via laparoscopy, in 61.6 percent of the investigated 350 patients in the course of 12 years. Describing the most characteristic mascoscopic varieties of chronic perihepatitis, the author groups them in seven separate form: I. Perihepatitis diffusa, corresponding to Zuckergussleber of Curschmann. II. Perihepatitis adhesiva and III. Perihepatitis circumscripta. The latter, on its part is subdivided to 5 separate forms of chronic perihepatitis: 1. Perihepatitis arachnoidealis, 2. Perihepatitis marginalis, 3. Perihepatitis areata et striata, 4. Perihepatitis miliaris disseminata, 5. Perihepatitis paravesicalis. That working laparoscopic classification contributes to the precise diagnostics and to the clinical interpretation of the separate forms of chronic perihepatitis. With the aid of lapraoscope the author performed a partial decapsulation of diffuse perihepatitis in 12 patients, without complications observed. Diffuse perihepatitis is, for the first time, described in patients with chronic hepatitis, in a patient with multiple liver abscesses and in one female-patient with peritoneal carcinosis and hemorrhagic ascites."} {"id": "PMID:160679", "title": "[Isolation of the causative agent of ornithosis from gamasid mites].", "content": "A microorganism was isolated from Gamasoid mites (Ornithonyssus sylviarum) collected in nests of blue rock pigeons by means of blind passages in white mice and chick embryos. The studies of its morphological, cultural, and antigenic properties and pathogenicity for laboratory animals permitted to identify it as the causative agent of ornithosis. It is suggested that the possibility of infection of ectoparasites is determined to a considerable extent by the degree of activity of the infectious process in the hosts. Ornithonyssus sylviarum may be assumed to be one of additional reservoirs of the causative agent of ornithosis in nature.", "contents": "[Isolation of the causative agent of ornithosis from gamasid mites]. A microorganism was isolated from Gamasoid mites (Ornithonyssus sylviarum) collected in nests of blue rock pigeons by means of blind passages in white mice and chick embryos. The studies of its morphological, cultural, and antigenic properties and pathogenicity for laboratory animals permitted to identify it as the causative agent of ornithosis. It is suggested that the possibility of infection of ectoparasites is determined to a considerable extent by the degree of activity of the infectious process in the hosts. Ornithonyssus sylviarum may be assumed to be one of additional reservoirs of the causative agent of ornithosis in nature."} {"id": "PMID:160686", "title": "[What is fluoroacetate diabetes?].", "content": "The opinion is incorrect that the monofluor carbon-induced hyperglucosaemia which in literature is cited under the term fluor acetate diabetes is caused by insulin deficiency due to lesion of the pancreatic beta-cells. The cause of the fluor acetate diabetes is a disturbance of the glucose degradation by inhibition of the enzyme phosphofructokinase. Insulin applications have no causal influence on the monofluor carbon intoxications and no symptomatic influence on the fluor acetate diabetes.", "contents": "[What is fluoroacetate diabetes?]. The opinion is incorrect that the monofluor carbon-induced hyperglucosaemia which in literature is cited under the term fluor acetate diabetes is caused by insulin deficiency due to lesion of the pancreatic beta-cells. The cause of the fluor acetate diabetes is a disturbance of the glucose degradation by inhibition of the enzyme phosphofructokinase. Insulin applications have no causal influence on the monofluor carbon intoxications and no symptomatic influence on the fluor acetate diabetes."} {"id": "PMID:160690", "title": "Further evidence for a S-syn correlation in the purine(beta)ribosides: the solution conformation of two tricyclic analogs of adenosine and guanosine.", "content": "From the analysis of the HRNMR spectra of two tricyclic analogues of adenosine and guanosine, 4,5-diamino-9-(beta-D-ribofuranosyl) pyrimido [5,4-f]pyrrolo[2,3-d]pyrimidine (adenosine-adenosine, AA) and 4,7-diamino-9-(beta-D-ribofuranosyl)pyrimido[5,4-f]pyrrolo-[2,3-d]pyrimidin-5-one (adenosine-guanosine, AG), dissolved in liquid ND3 the preferred conformations of the ribose moiety are derived in the temperature range between + 40 and -60 degrees C. The analysis is based on the two state N in equilibrium or formed from S model of the furanoside ring proposed by Altona and Sundaralingam. Both compounds show a pronounced stabilization of the S-conformer of the sugar ring ([S] approximately 0.8). The van't Hoff enthalpy for the S in equilibrium or formed from N equilibrium is -3 kJ mol-1. The syn in equilibrium or formed from anti equilibrium is even at -60 degrees C fast compared to the HRNMR time scale.", "contents": "Further evidence for a S-syn correlation in the purine(beta)ribosides: the solution conformation of two tricyclic analogs of adenosine and guanosine. From the analysis of the HRNMR spectra of two tricyclic analogues of adenosine and guanosine, 4,5-diamino-9-(beta-D-ribofuranosyl) pyrimido [5,4-f]pyrrolo[2,3-d]pyrimidine (adenosine-adenosine, AA) and 4,7-diamino-9-(beta-D-ribofuranosyl)pyrimido[5,4-f]pyrrolo-[2,3-d]pyrimidin-5-one (adenosine-guanosine, AG), dissolved in liquid ND3 the preferred conformations of the ribose moiety are derived in the temperature range between + 40 and -60 degrees C. The analysis is based on the two state N in equilibrium or formed from S model of the furanoside ring proposed by Altona and Sundaralingam. Both compounds show a pronounced stabilization of the S-conformer of the sugar ring ([S] approximately 0.8). The van't Hoff enthalpy for the S in equilibrium or formed from N equilibrium is -3 kJ mol-1. The syn in equilibrium or formed from anti equilibrium is even at -60 degrees C fast compared to the HRNMR time scale."} {"id": "PMID:160692", "title": "Potential anticancer agents, XI. X-ray structure determination of acantholide.", "content": "The X-ray structure of acantholide, a melampolide sesquiterpene lactone from Acanthospermum glabratum (DC.) Willd. was determined by the aid of direct methods. The compound was cytotoxic but displayed no antitumor activity. Evaluation of the X-ray and NMR data indicated that the same conformation exists in the solid state as in solution.", "contents": "Potential anticancer agents, XI. X-ray structure determination of acantholide. The X-ray structure of acantholide, a melampolide sesquiterpene lactone from Acanthospermum glabratum (DC.) Willd. was determined by the aid of direct methods. The compound was cytotoxic but displayed no antitumor activity. Evaluation of the X-ray and NMR data indicated that the same conformation exists in the solid state as in solution."} {"id": "PMID:160693", "title": "A model mechanism for the enzymatic synthesis of lupin alkaloids.", "content": "A crude enzyme preparation obtained from cell suspension cultures of Lupinus polyphyllus catalyzes the pyruvate dependent conversion of cadaverine into the tetracyclic lupin alkaloids. As the first reaction product 17-oxosparteine could be identified by gas-liquid chromatography and mass spectroscopy. In some experiments sparteine was found additionally. A participation of diamine oxidase could be ruled out. The cadaverine-pyruvate transaminating enzyme system (17-oxosparteine synthase) catalyzes the formation of 17-oxosparteine from three cadaverine units without releasing free intermediates. These results are inconsistent with the hypothetical mechanism thus far formulated for the lupin alkaloid biosynthesis. A new enzymatic model mechanism is proposed regarding both the results of the enzymatic experiments and those of the in vivo tracer studies.", "contents": "A model mechanism for the enzymatic synthesis of lupin alkaloids. A crude enzyme preparation obtained from cell suspension cultures of Lupinus polyphyllus catalyzes the pyruvate dependent conversion of cadaverine into the tetracyclic lupin alkaloids. As the first reaction product 17-oxosparteine could be identified by gas-liquid chromatography and mass spectroscopy. In some experiments sparteine was found additionally. A participation of diamine oxidase could be ruled out. The cadaverine-pyruvate transaminating enzyme system (17-oxosparteine synthase) catalyzes the formation of 17-oxosparteine from three cadaverine units without releasing free intermediates. These results are inconsistent with the hypothetical mechanism thus far formulated for the lupin alkaloid biosynthesis. A new enzymatic model mechanism is proposed regarding both the results of the enzymatic experiments and those of the in vivo tracer studies."} {"id": "PMID:160691", "title": "A theoretical study of H3PO4, nor-N-mustard, and cyclophosphamide.", "content": "Some physical and chemical properties of the cancerostat cyclophosphamide (generic name: ENDOXAN) and its basic constituents H3PO4 and nor-N-mustard have been calculated with the help of a modified CNDO/S-method. The spectroscopic data of the H3PO4, which is the starting-point for a corresponding calculation of cyclophosphamide, has been studied by taking account of the 3 d electron of the phosphorus. Nor-N-mustard is a very reactive compound, characterized by the ability to split off chloride ions and to act as an alkylating agent. The binding of the nor-N-mustard to the cyclic phosphate ester (cyclophosphamide) modifies the chemical reactivity of the mustard group in an essential way, and the 3 d electron of the phosphorus plays an important role with respect to the excitability of the C--Cl bonds. Cyclophosphamide must be metabolized in a suitable way to develop the same alkylating activity as the nor-N-mustard. The computation of the excited states of cyclophosphamide revealed a similar term scheme as it was found by Clar in the case of the carcinogenic polycyclic hydrocarbons.", "contents": "A theoretical study of H3PO4, nor-N-mustard, and cyclophosphamide. Some physical and chemical properties of the cancerostat cyclophosphamide (generic name: ENDOXAN) and its basic constituents H3PO4 and nor-N-mustard have been calculated with the help of a modified CNDO/S-method. The spectroscopic data of the H3PO4, which is the starting-point for a corresponding calculation of cyclophosphamide, has been studied by taking account of the 3 d electron of the phosphorus. Nor-N-mustard is a very reactive compound, characterized by the ability to split off chloride ions and to act as an alkylating agent. The binding of the nor-N-mustard to the cyclic phosphate ester (cyclophosphamide) modifies the chemical reactivity of the mustard group in an essential way, and the 3 d electron of the phosphorus plays an important role with respect to the excitability of the C--Cl bonds. Cyclophosphamide must be metabolized in a suitable way to develop the same alkylating activity as the nor-N-mustard. The computation of the excited states of cyclophosphamide revealed a similar term scheme as it was found by Clar in the case of the carcinogenic polycyclic hydrocarbons."} {"id": "PMID:160695", "title": "[Acetylcholinesterase from bovine erythrocytes. Purification and properties of the enzyme solubilized in the presence and the absence of Triton X-100 (author's transl)].", "content": "Acetylcholinesterase was released from bovine erythrocytes by Triton X-100 treatment and purified by twwfold affinity chromatography. The detergentfree enzyme was obtained with a specific activity of 4130 U/mg (303 000-fold purification) and a 25% yield. Alternatively, the commercial available crude enzyme was purified. The latter preparation has an uniform molecular weight (Mr 175 000). The Triton-solubilized enzyme, however, can be resolved after removal of the detergent in eight multiple forms (Mr 175 000 and multiple values), in the presence of Triton there exists only one form (Mr 338 000). The amino acid composition of the two enzyme preparations differs significantly. No differences were observed with respect to other properties: SDS gel electrophoresis revealed two protein bands (Mr 166 000 and 86 000) with both preparations. The enzyme is a glycoprotein with a pI value of 4.3 and contains strongly bound phosphatidylethanolamine. The N-terminal amino acid has been found to be Glu (or Gln).", "contents": "[Acetylcholinesterase from bovine erythrocytes. Purification and properties of the enzyme solubilized in the presence and the absence of Triton X-100 (author's transl)]. Acetylcholinesterase was released from bovine erythrocytes by Triton X-100 treatment and purified by twwfold affinity chromatography. The detergentfree enzyme was obtained with a specific activity of 4130 U/mg (303 000-fold purification) and a 25% yield. Alternatively, the commercial available crude enzyme was purified. The latter preparation has an uniform molecular weight (Mr 175 000). The Triton-solubilized enzyme, however, can be resolved after removal of the detergent in eight multiple forms (Mr 175 000 and multiple values), in the presence of Triton there exists only one form (Mr 338 000). The amino acid composition of the two enzyme preparations differs significantly. No differences were observed with respect to other properties: SDS gel electrophoresis revealed two protein bands (Mr 166 000 and 86 000) with both preparations. The enzyme is a glycoprotein with a pI value of 4.3 and contains strongly bound phosphatidylethanolamine. The N-terminal amino acid has been found to be Glu (or Gln)."} {"id": "PMID:160694", "title": "Purification and properties of a catechol methyltransferase of the yeast Candida tropicalis.", "content": "In an effort to investigate catechol methyltransferase activity in sources other than mammalian tissues and cells, a high level of enzyme activity was found in the yeast fungus Candida tropicalis CBS 94. Partial purification of the enzyme (approx. 550 fold with a recovery of 7%) could be achieved by using ion-exchange and gel filtration techniques. The molecular weight was estimated at 32,000 +/- 2,000 by gel filtration on Sephadex G-100. In isoelectric focusing experiments on Sephadex G-75 the enzyme exhibited a pI-value of 5.0 +/- 0.1. In contrast to catechol methyltransferase from various mammalian tissues the enzyme activity was prepared from the pH 5-sediment. The substrate specifity is comparable to other catechol methyltransferases.", "contents": "Purification and properties of a catechol methyltransferase of the yeast Candida tropicalis. In an effort to investigate catechol methyltransferase activity in sources other than mammalian tissues and cells, a high level of enzyme activity was found in the yeast fungus Candida tropicalis CBS 94. Partial purification of the enzyme (approx. 550 fold with a recovery of 7%) could be achieved by using ion-exchange and gel filtration techniques. The molecular weight was estimated at 32,000 +/- 2,000 by gel filtration on Sephadex G-100. In isoelectric focusing experiments on Sephadex G-75 the enzyme exhibited a pI-value of 5.0 +/- 0.1. In contrast to catechol methyltransferase from various mammalian tissues the enzyme activity was prepared from the pH 5-sediment. The substrate specifity is comparable to other catechol methyltransferases."} {"id": "PMID:160696", "title": "Purification and properties of the soluble 17 beta-hydroxysteroid dehydrogenase of rabbit uterus.", "content": "17 beta-Hydroxysteroid dehydrogenase activity towards estradiol-17 beta has been demonstrated in the 105,000 x g supernatant of rabbit uterus. Hydroxylapatite chromatography of the enzyme activity isolated by ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography yielded a single 17 beta-hydroxysteroid dehydrogenase activity. Further purification of the enzyme preparation by isoelectric focusing resulted in multiple peaks of activity. The molecular weight of the enzyme, caculated from mobility data on Sephadex gel, is approximately 64,000. Some properties of partially purified 17 beta-hydroxysteroid dehydrogenase activity have been studied. Estradiol-17 beta reacts at a faster rate than testosterone. The Km for estradiol is 4.16 x 10(-5) mol/l for the NAD-linked enzyme activity and 4.37 x 10(-5) mol/l when NADP as cofactor was used. The ratio of the maximal velocity for NADP to that for NAD was 1.42. The pH-optimum for estradiol appears between 9.5 and 10.5 and for estrone between 5.5 and 6.5. The enzyme appears to be of the sulfhydryl type.", "contents": "Purification and properties of the soluble 17 beta-hydroxysteroid dehydrogenase of rabbit uterus. 17 beta-Hydroxysteroid dehydrogenase activity towards estradiol-17 beta has been demonstrated in the 105,000 x g supernatant of rabbit uterus. Hydroxylapatite chromatography of the enzyme activity isolated by ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography yielded a single 17 beta-hydroxysteroid dehydrogenase activity. Further purification of the enzyme preparation by isoelectric focusing resulted in multiple peaks of activity. The molecular weight of the enzyme, caculated from mobility data on Sephadex gel, is approximately 64,000. Some properties of partially purified 17 beta-hydroxysteroid dehydrogenase activity have been studied. Estradiol-17 beta reacts at a faster rate than testosterone. The Km for estradiol is 4.16 x 10(-5) mol/l for the NAD-linked enzyme activity and 4.37 x 10(-5) mol/l when NADP as cofactor was used. The ratio of the maximal velocity for NADP to that for NAD was 1.42. The pH-optimum for estradiol appears between 9.5 and 10.5 and for estrone between 5.5 and 6.5. The enzyme appears to be of the sulfhydryl type."} {"id": "PMID:160697", "title": "UDP-glucose: glucosyltransferase activity involved in the biosynthesis of flavonol triglucosides in Pisum sativum L. seedlings.", "content": "From young, light-grown seedlings of Pisum sativum L. an enzyme activity catalyzing the glucosylation of kaempferol and quercetin in the 3-position to form the 3-0-triglucoside derivative has been demonstrated. The reaction proceeds from the aglycone via the mono- and diglucoside intermediates. The triglucoside can be produced from any of the less substituted derivatives with uridine diphosphate-D-glucose (UDPG) as the glucosyl donor. Young leaf tissues had much higher levels of glucosyltransferase activity than the petioles and internodes. This is the first report of the synthesis of flavonol-3-0-triglucosides in vitro.", "contents": "UDP-glucose: glucosyltransferase activity involved in the biosynthesis of flavonol triglucosides in Pisum sativum L. seedlings. From young, light-grown seedlings of Pisum sativum L. an enzyme activity catalyzing the glucosylation of kaempferol and quercetin in the 3-position to form the 3-0-triglucoside derivative has been demonstrated. The reaction proceeds from the aglycone via the mono- and diglucoside intermediates. The triglucoside can be produced from any of the less substituted derivatives with uridine diphosphate-D-glucose (UDPG) as the glucosyl donor. Young leaf tissues had much higher levels of glucosyltransferase activity than the petioles and internodes. This is the first report of the synthesis of flavonol-3-0-triglucosides in vitro."} {"id": "PMID:160698", "title": "Inhibition of E. coli L-Asparaginase by reaction with 2,3-butanedione. Chemical modification of arginine and histidine residues.", "content": "The inactivation of E. coli asparaginase by 2,3-butanedione studied with L-asparagine and diazooxonorvaline as substrates obeys pseudo first order kinetics. Activity losses are linear with respect to arginine and histidine modification, with complete inactivation being correlated with alteration of one arginine and one histidine per subunit. The rate of inactivation of the enzyme was reduced in the presence of competitive inhibitors like L-2-amino-2-carboxyethane-sulfonamide. Under comparable conditions 1,2-cyclo hexanedione does not affect the activity of L-asparaginase.", "contents": "Inhibition of E. coli L-Asparaginase by reaction with 2,3-butanedione. Chemical modification of arginine and histidine residues. The inactivation of E. coli asparaginase by 2,3-butanedione studied with L-asparagine and diazooxonorvaline as substrates obeys pseudo first order kinetics. Activity losses are linear with respect to arginine and histidine modification, with complete inactivation being correlated with alteration of one arginine and one histidine per subunit. The rate of inactivation of the enzyme was reduced in the presence of competitive inhibitors like L-2-amino-2-carboxyethane-sulfonamide. Under comparable conditions 1,2-cyclo hexanedione does not affect the activity of L-asparaginase."} {"id": "PMID:160699", "title": "[Influence of twovalent foreign cations on the uptake of zinc by Chlorella (author's transl)].", "content": "The influence of 10(-4) divalent cations on the uptake of labelled Zn in the concentration range 10(-5) to 5 x 10(-5) M into the interior of Chlorella fusca at 30 degrees C was measured during 75 min. The Zn absorbed on the surface or contained in the free space was removed by washing with EDTA. Corrections were applied for the loss in concentration due to surface adsorption, etc. The results were consistent with competitive inhibition of Zn uptake by the foreign ions. No allosteric inhibition was found. From the Lineweaver-Burk diagram, for uninhibited Zn, KM was found as 7 x 10(-6) M and Vmax as 8.3 x 10(-9) mol.min-1.g-1 algae. The inhibitor constants were: Mg 1.3 x 10(-5), Ca 4.3 x 10(-5), Co 4.3 x 10(-5), Ni 4.3 x 10(-5), Cd 1.3 x 10(-5) and Pb 9.4 x 10(-7) M. The values given for Km and the inhibitor constant refer to the velocities of uptake after 45 min.", "contents": "[Influence of twovalent foreign cations on the uptake of zinc by Chlorella (author's transl)]. The influence of 10(-4) divalent cations on the uptake of labelled Zn in the concentration range 10(-5) to 5 x 10(-5) M into the interior of Chlorella fusca at 30 degrees C was measured during 75 min. The Zn absorbed on the surface or contained in the free space was removed by washing with EDTA. Corrections were applied for the loss in concentration due to surface adsorption, etc. The results were consistent with competitive inhibition of Zn uptake by the foreign ions. No allosteric inhibition was found. From the Lineweaver-Burk diagram, for uninhibited Zn, KM was found as 7 x 10(-6) M and Vmax as 8.3 x 10(-9) mol.min-1.g-1 algae. The inhibitor constants were: Mg 1.3 x 10(-5), Ca 4.3 x 10(-5), Co 4.3 x 10(-5), Ni 4.3 x 10(-5), Cd 1.3 x 10(-5) and Pb 9.4 x 10(-7) M. The values given for Km and the inhibitor constant refer to the velocities of uptake after 45 min."} {"id": "PMID:160701", "title": "Effects of alpha-aminooxy-beta-phenylpropionic acid on phenylalanine metabolism in p-fluorophenylalanine sensitive and resistant tobacco cells.", "content": "A p-fluorophenylalanine (PFP) resistant cell line with high phenylalanine ammonia lyase (PAL) activity and wild type cells with low PAL activity were compared in their responses to PAL inhibition by alpha-aminooxy-beta-phenylpropionic acid (AOP). Inhibition of PAL reduced the levels of the main phenolic compounds to 30% of the controls. Free phenylalanine pools increased 17 fold in the resistant line and 6 fold in the sensitive line, respectively. The accumulation of phenylalanine did not reduce the flow of labeled shikimic acid into the aromatic amino acids tyrosine and phenylalanine. The results are discussed with respect to the feedback inhibition of chorismate mutase activity by phenylalanine and tyrosine in both cell lines.", "contents": "Effects of alpha-aminooxy-beta-phenylpropionic acid on phenylalanine metabolism in p-fluorophenylalanine sensitive and resistant tobacco cells. A p-fluorophenylalanine (PFP) resistant cell line with high phenylalanine ammonia lyase (PAL) activity and wild type cells with low PAL activity were compared in their responses to PAL inhibition by alpha-aminooxy-beta-phenylpropionic acid (AOP). Inhibition of PAL reduced the levels of the main phenolic compounds to 30% of the controls. Free phenylalanine pools increased 17 fold in the resistant line and 6 fold in the sensitive line, respectively. The accumulation of phenylalanine did not reduce the flow of labeled shikimic acid into the aromatic amino acids tyrosine and phenylalanine. The results are discussed with respect to the feedback inhibition of chorismate mutase activity by phenylalanine and tyrosine in both cell lines."} {"id": "PMID:160702", "title": "Chemical modification of biliprotein chromophores.", "content": "The reaction of biliproteins with sodium dithionite has been studied. The reagent is selective towards the chromophores. In denatured phycocyanin from Spirulina platensis, all three chromophores react to form yellow \"phycorubin\", whereas only 1/3 of the chromophores react in native phycocyanin in a non-statistical manner. From reversion experiments, it can be shown, that the thermodynamic stability of the chromophores towards reaction with dithionite is increased in the native pigment. Similarly, native phytochrome in its Pr form reacts only partially to a pigment absorbing at both 420 and 660 nm. The same product is formed from native Pfr, indicating both a reversion to Pr and a partial reduction.", "contents": "Chemical modification of biliprotein chromophores. The reaction of biliproteins with sodium dithionite has been studied. The reagent is selective towards the chromophores. In denatured phycocyanin from Spirulina platensis, all three chromophores react to form yellow \"phycorubin\", whereas only 1/3 of the chromophores react in native phycocyanin in a non-statistical manner. From reversion experiments, it can be shown, that the thermodynamic stability of the chromophores towards reaction with dithionite is increased in the native pigment. Similarly, native phytochrome in its Pr form reacts only partially to a pigment absorbing at both 420 and 660 nm. The same product is formed from native Pfr, indicating both a reversion to Pr and a partial reduction."} {"id": "PMID:160700", "title": "On the analysis of competitive binding of various ligands to cooperative and independent binding sites of macromolecules.", "content": "The paper deals with the practical evaluation of multiple binding equilibria of macromolecules and different ligands competing for the same binding sites. The necessary formalism is reviewed and set up for the equilibria involving a macromolecule with various classes of independent binding sites and/or a class of cooperative sites and up to three different ligands in competition for them. In particular, it was necessary to extend the Hill approximation to treat simultaneous competition for cooperative as well as independent binding sites, while earlier attempts are shown to be inadequate. Criteria are developed for a qualitative analysis of complex binding patterns using the Scatchard-plot of the experimental data in order to obtain a model of the binding structure and an adequate set of input parameters for the numerical analysis. Numerical examples refer to the binding of calcium and magnesium to the sarcoplasmic reticulum as studied by competitive replacement of manganese ions [3].", "contents": "On the analysis of competitive binding of various ligands to cooperative and independent binding sites of macromolecules. The paper deals with the practical evaluation of multiple binding equilibria of macromolecules and different ligands competing for the same binding sites. The necessary formalism is reviewed and set up for the equilibria involving a macromolecule with various classes of independent binding sites and/or a class of cooperative sites and up to three different ligands in competition for them. In particular, it was necessary to extend the Hill approximation to treat simultaneous competition for cooperative as well as independent binding sites, while earlier attempts are shown to be inadequate. Criteria are developed for a qualitative analysis of complex binding patterns using the Scatchard-plot of the experimental data in order to obtain a model of the binding structure and an adequate set of input parameters for the numerical analysis. Numerical examples refer to the binding of calcium and magnesium to the sarcoplasmic reticulum as studied by competitive replacement of manganese ions [3]."} {"id": "PMID:160704", "title": "Proliferation and metabolic activities of Ehrlich ascites tumor cells in chemically defined albumin media.", "content": "Cell proliferation, viability, DNA-, RNA-, protein synthesis, amino acid transport, repiration and lactate/glucose quotient of Ehrlich ascites tumor cells grown in suspension culture in serum free medium supplemented with albumin charges of different origin were studied. Optimal cell growth was obtained in nutrient medium supplemented with 1% bovine serum albumin (Cohn-fraction V, Serva). Cell proliferation under these culture conditions was delayed to 50% as compared to controls in normal medium; the rate of synthesis of macromolecules was reduced; energy metabolism was not significantly imparied. The trend of the cells in albumin medium to attach to glass was independent from the pH of the cultures between 7.2 and 8.0; it was enhanced by fatty acid deprivation of the albumin.", "contents": "Proliferation and metabolic activities of Ehrlich ascites tumor cells in chemically defined albumin media. Cell proliferation, viability, DNA-, RNA-, protein synthesis, amino acid transport, repiration and lactate/glucose quotient of Ehrlich ascites tumor cells grown in suspension culture in serum free medium supplemented with albumin charges of different origin were studied. Optimal cell growth was obtained in nutrient medium supplemented with 1% bovine serum albumin (Cohn-fraction V, Serva). Cell proliferation under these culture conditions was delayed to 50% as compared to controls in normal medium; the rate of synthesis of macromolecules was reduced; energy metabolism was not significantly imparied. The trend of the cells in albumin medium to attach to glass was independent from the pH of the cultures between 7.2 and 8.0; it was enhanced by fatty acid deprivation of the albumin."} {"id": "PMID:160705", "title": "T2 phage sensitization by linear and angular furocoumarins.", "content": "T2 bacteriophage sensitization has been studied using two furocoumarins capable of linking covalently to DNA to the same extent but producing different damages, psoralen and 4,5'-dimethylangelicin. Psoralen is a well-known linear furocoumarin capable of inducing in DNA both monoadducts and cross-links; 4,5'-dimethylangelicin is a new angular compound known as a pure monofunctional reagent. In the sensitization of T2 mature virions both drugs proved very active, yielding survival curves practically superimposable; on the contrary, in the experiments with the T2 vegetative form, i. e. its DNA inside the host, 4,5'-dimethylangelicin resulted much less effective, resembling the picture observed in the inactivation of the host bacteria. This result did not appear related to an enhancement of DNA repair by a Weigle effect. The different killing activity of 4,5'-dimethylangelicin can be explained supposing that this drug is capable of inducing cross-links in T2 DNA inside the virus core, in which it exists in a very folded form, but not in the same DNA after injection into the host bacteria.", "contents": "T2 phage sensitization by linear and angular furocoumarins. T2 bacteriophage sensitization has been studied using two furocoumarins capable of linking covalently to DNA to the same extent but producing different damages, psoralen and 4,5'-dimethylangelicin. Psoralen is a well-known linear furocoumarin capable of inducing in DNA both monoadducts and cross-links; 4,5'-dimethylangelicin is a new angular compound known as a pure monofunctional reagent. In the sensitization of T2 mature virions both drugs proved very active, yielding survival curves practically superimposable; on the contrary, in the experiments with the T2 vegetative form, i. e. its DNA inside the host, 4,5'-dimethylangelicin resulted much less effective, resembling the picture observed in the inactivation of the host bacteria. This result did not appear related to an enhancement of DNA repair by a Weigle effect. The different killing activity of 4,5'-dimethylangelicin can be explained supposing that this drug is capable of inducing cross-links in T2 DNA inside the virus core, in which it exists in a very folded form, but not in the same DNA after injection into the host bacteria."} {"id": "PMID:160703", "title": "[Quantitative comparison of ribosome binding sites of twelve nucleotide sequences from Escherichia coli (RNA- and DNA phages) based on triplet patterns (author's transl)].", "content": "The molecular structure of ribosome binding sites of ten phage genes and two messengers of Escherichia coli were compared concerning the signation parts which are presumably used by ribosomes for recognition and binding. With a simple calculation based on triplet patterns sofar unknown agreements between all of these sequences were found. In several cases it was shown that agreements between old sequences are easier recognizable if the purine- and pyrimidine bases are put into the triplets instead of the four A, G, C, and U (T) bases. In such cases \"homologous\" parts of sequences were recognized with more distinctness. This is true in our case for the double triplet (hexaplet) py-pu-pu-pu-pu-(pu) and the binding site triplet py-pu-pu, which are preceding the initiator. These triplets are in specific positions in all twelve sequences which were compared. The different course of the quaternary and the binary conformity curves (diagram 1) may show for the investigated area that the RNA phage gene-part is organized according to the well known quaternary triplet code. On the contrary the phage phi-gene-part seems to be organized according to a more simple, binary triplet sequence of purine and pyrimidine bases. The binary sequence seems to be the more original, the quaternary the derived one.", "contents": "[Quantitative comparison of ribosome binding sites of twelve nucleotide sequences from Escherichia coli (RNA- and DNA phages) based on triplet patterns (author's transl)]. The molecular structure of ribosome binding sites of ten phage genes and two messengers of Escherichia coli were compared concerning the signation parts which are presumably used by ribosomes for recognition and binding. With a simple calculation based on triplet patterns sofar unknown agreements between all of these sequences were found. In several cases it was shown that agreements between old sequences are easier recognizable if the purine- and pyrimidine bases are put into the triplets instead of the four A, G, C, and U (T) bases. In such cases \"homologous\" parts of sequences were recognized with more distinctness. This is true in our case for the double triplet (hexaplet) py-pu-pu-pu-pu-(pu) and the binding site triplet py-pu-pu, which are preceding the initiator. These triplets are in specific positions in all twelve sequences which were compared. The different course of the quaternary and the binary conformity curves (diagram 1) may show for the investigated area that the RNA phage gene-part is organized according to the well known quaternary triplet code. On the contrary the phage phi-gene-part seems to be organized according to a more simple, binary triplet sequence of purine and pyrimidine bases. The binary sequence seems to be the more original, the quaternary the derived one."} {"id": "PMID:160709", "title": "[The sequence of a dimeric hemoglobin (erythrocruorin), component IX, from Chironomus thummi thummi (Insecta Diptera) (author's transl)].", "content": "The primary structure of the dimeric hemoglobin (erythrocruorin) CTT-IX from the insect larva Chironomus thummi thummi (Insecta Diptera) is given. The sequence was determined automatically. The primary structure is compared with human alpha-chains.", "contents": "[The sequence of a dimeric hemoglobin (erythrocruorin), component IX, from Chironomus thummi thummi (Insecta Diptera) (author's transl)]. The primary structure of the dimeric hemoglobin (erythrocruorin) CTT-IX from the insect larva Chironomus thummi thummi (Insecta Diptera) is given. The sequence was determined automatically. The primary structure is compared with human alpha-chains."} {"id": "PMID:160711", "title": "Radiation induced loss of anti-Ig binding ability of lymphocytes.", "content": "The effect of irradiation on the anti Ig binding ability of lymphocytes after irradiation was studied. Normal control and irradiated lymphoid cells were treated with rabbit anti mouse IgG fluorescein conjugated serum and the fluorescein positive cells compared. A reduction in the proportion of stained cells in the irradiated lymphocytes was found. It depends on the dose and on the incubation time at 37 degrees C after irradiation. The maximum effect was detected after 10 minutes of incubation, longer incubation is associated with a partial recovery of the stainability of the IgG receptors.", "contents": "Radiation induced loss of anti-Ig binding ability of lymphocytes. The effect of irradiation on the anti Ig binding ability of lymphocytes after irradiation was studied. Normal control and irradiated lymphoid cells were treated with rabbit anti mouse IgG fluorescein conjugated serum and the fluorescein positive cells compared. A reduction in the proportion of stained cells in the irradiated lymphocytes was found. It depends on the dose and on the incubation time at 37 degrees C after irradiation. The maximum effect was detected after 10 minutes of incubation, longer incubation is associated with a partial recovery of the stainability of the IgG receptors."} {"id": "PMID:160707", "title": "Fine structure and organization of the sarcoplasmic reticulum in the sino-auricular fibres of frog heart.", "content": "The ultrastructure of the sarcoplasmic reticulum (SR) of the sino-auricular fibres of frog heart has been investigated especially in order to evaluate its possible relationship with several cellular organelles. The SR appears as a complex unit which can be divided into three regions:--peripheral SR, localized beneath the sarcolemma. It is composed of junctional SR, which forms specialized complexes (couplings) with the sarcolemma, and peripheral SR s. str. which frequently extends its anastomotic tubules around the caveolae.--juxtafibrillar SR, in relation with myofibrils, at the level of Z lines and I bands.--intermediary SR which is the most abundant. It contains dense granules, able to bind strontium (and calcium) and, from place to place, is formed into flattened saccules bearing fenestrations where microfilaments frequently pass through. It allows peripheral SR and juxtafibrillar SR to communicate, giving unity to the reticular system and, on the other hand, shows close topographical relations with mitochondria. The great extension of the SR, its heterogeneity and its relationships with several cellular organelles, especially mitochondria, are interpreted from the functional point of view.", "contents": "Fine structure and organization of the sarcoplasmic reticulum in the sino-auricular fibres of frog heart. The ultrastructure of the sarcoplasmic reticulum (SR) of the sino-auricular fibres of frog heart has been investigated especially in order to evaluate its possible relationship with several cellular organelles. The SR appears as a complex unit which can be divided into three regions:--peripheral SR, localized beneath the sarcolemma. It is composed of junctional SR, which forms specialized complexes (couplings) with the sarcolemma, and peripheral SR s. str. which frequently extends its anastomotic tubules around the caveolae.--juxtafibrillar SR, in relation with myofibrils, at the level of Z lines and I bands.--intermediary SR which is the most abundant. It contains dense granules, able to bind strontium (and calcium) and, from place to place, is formed into flattened saccules bearing fenestrations where microfilaments frequently pass through. It allows peripheral SR and juxtafibrillar SR to communicate, giving unity to the reticular system and, on the other hand, shows close topographical relations with mitochondria. The great extension of the SR, its heterogeneity and its relationships with several cellular organelles, especially mitochondria, are interpreted from the functional point of view."} {"id": "PMID:160708", "title": "The primary structure of the beta-lactoglobulin of the waterbuffalo (Bubalus arnee).", "content": "The complete amino acid sequence of the beta-lactoglobuline of the waterbuffalo (Bubalus arnee) was established. The sequence of peptides obtained by cleavage with BNPS-Skatole, CNBr and trypsin were determined automatically by the help of the sequenator. Only two differences were found in the beta lactoglobulin of the waterbuffalo compared with the bovine beta-lactoglobulin B.", "contents": "The primary structure of the beta-lactoglobulin of the waterbuffalo (Bubalus arnee). The complete amino acid sequence of the beta-lactoglobuline of the waterbuffalo (Bubalus arnee) was established. The sequence of peptides obtained by cleavage with BNPS-Skatole, CNBr and trypsin were determined automatically by the help of the sequenator. Only two differences were found in the beta lactoglobulin of the waterbuffalo compared with the bovine beta-lactoglobulin B."} {"id": "PMID:160710", "title": "Radioactive labelling of lipids in rat neurosarcoma by intravenous injection of [1-14C]-octadecenol.", "content": "Radioactivity from cis-9-[1-14C]octadecenol, injected intravenously into rats bearing neurosarcoma, is incorporated to a significantly greater extent into tumor than into muscle. In the lipids of both tissues, radioactivity is incorporated predominantly into the acyl moieties, rather than into the alkyl or alk-1-enyl moieties, of diradylglycerophosphocholines, diradylglycerophosphoethanolamines, and triradylglycerols.", "contents": "Radioactive labelling of lipids in rat neurosarcoma by intravenous injection of [1-14C]-octadecenol. Radioactivity from cis-9-[1-14C]octadecenol, injected intravenously into rats bearing neurosarcoma, is incorporated to a significantly greater extent into tumor than into muscle. In the lipids of both tissues, radioactivity is incorporated predominantly into the acyl moieties, rather than into the alkyl or alk-1-enyl moieties, of diradylglycerophosphocholines, diradylglycerophosphoethanolamines, and triradylglycerols."} {"id": "PMID:160712", "title": "Color vision in salamander larvae.", "content": "In behavioral experiments using monochromatic prey-patterns, larval salamanders (Salamandra salamandra) are able to discriminate colored from white light. In the retina only blue-yellow opponent-color ganglion cells were recorded. Thus the color vision in these animals is dichromatic.", "contents": "Color vision in salamander larvae. In behavioral experiments using monochromatic prey-patterns, larval salamanders (Salamandra salamandra) are able to discriminate colored from white light. In the retina only blue-yellow opponent-color ganglion cells were recorded. Thus the color vision in these animals is dichromatic."} {"id": "PMID:160725", "title": "[Iatrogeni vascular injuries (author's transl)].", "content": "We report on 34 intraogenic vascular injuries. In nine cases vascular trauma occured secondary to diagnostic procedures. The other 25 cases were due to therapeutic measures. Vascular reconstruction was successfull in all cases, except 2, which required above-knee amputation because of ischaemic damage. The causes of death in 4 cases were malignant diseases or multiple traumatic injuries.", "contents": "[Iatrogeni vascular injuries (author's transl)]. We report on 34 intraogenic vascular injuries. In nine cases vascular trauma occured secondary to diagnostic procedures. The other 25 cases were due to therapeutic measures. Vascular reconstruction was successfull in all cases, except 2, which required above-knee amputation because of ischaemic damage. The causes of death in 4 cases were malignant diseases or multiple traumatic injuries."} {"id": "PMID:160724", "title": "[Significance of malformations and variations in the lumbosacral spine for the pathogenesis of intervertebral disk diseases].", "content": "Clinical data and x-ray findings of 1000 patients with back pain have been analysed. The authors found evidence that malformations and particularly development variations of the lumbosacral vertebral column may play a role in the pathogenesis of intervertebral disk degenerations. The discopathies become clinically manifest as a consequence of development faults at a younger age und in a larger number than in those with normal development of the spine. The clinical importance of the transitional vertebra is discussed.", "contents": "[Significance of malformations and variations in the lumbosacral spine for the pathogenesis of intervertebral disk diseases]. Clinical data and x-ray findings of 1000 patients with back pain have been analysed. The authors found evidence that malformations and particularly development variations of the lumbosacral vertebral column may play a role in the pathogenesis of intervertebral disk degenerations. The discopathies become clinically manifest as a consequence of development faults at a younger age und in a larger number than in those with normal development of the spine. The clinical importance of the transitional vertebra is discussed."} {"id": "PMID:160729", "title": "Four bakers showing positive patch-tests to a number of fragrance materials, which can also be used as flavors.", "content": "Contact sensitization to fragrance materials may be caused by occupational exposure to flavor compositions in the food trade and needs not to be due to cosmetic exposure exclusively. To illustrate this, investigative results in four bakers are discussed.", "contents": "Four bakers showing positive patch-tests to a number of fragrance materials, which can also be used as flavors. Contact sensitization to fragrance materials may be caused by occupational exposure to flavor compositions in the food trade and needs not to be due to cosmetic exposure exclusively. To illustrate this, investigative results in four bakers are discussed."} {"id": "PMID:160730", "title": "Acne aestivalis. A histopathological study.", "content": "Twelve histological sections with the diagnosis acne aestivalis (Mallorca acne) were revised and compared with the clinical diagnosis. Two histological diagnosis were wrong, one being folliculitis necroticans the other an uncharacteristic follicular disease. Non the less this patient had clinical acne aestivalis. In five patients accordance was found between histopathology and the clinical picture. Among the last five patients with histological acne aestivalis one had clinical rosacea, one yersinosis and dermatitis herpetiformis, one acne vulgaris, one miliaria or transcient acantholytic dermatosis, and the last one folliculitis perforans. The two last mentioned patients had the same histological picture which could be consistent with folliculitis perforans. The similarity in histopathology in this disease and acne aestivalis is emphasized. The histopathology in acne aestivalis could indicate, that the disease starts as a damage in corium and that the changes in the pilosebaceous apparatus are secondary.", "contents": "Acne aestivalis. A histopathological study. Twelve histological sections with the diagnosis acne aestivalis (Mallorca acne) were revised and compared with the clinical diagnosis. Two histological diagnosis were wrong, one being folliculitis necroticans the other an uncharacteristic follicular disease. Non the less this patient had clinical acne aestivalis. In five patients accordance was found between histopathology and the clinical picture. Among the last five patients with histological acne aestivalis one had clinical rosacea, one yersinosis and dermatitis herpetiformis, one acne vulgaris, one miliaria or transcient acantholytic dermatosis, and the last one folliculitis perforans. The two last mentioned patients had the same histological picture which could be consistent with folliculitis perforans. The similarity in histopathology in this disease and acne aestivalis is emphasized. The histopathology in acne aestivalis could indicate, that the disease starts as a damage in corium and that the changes in the pilosebaceous apparatus are secondary."} {"id": "PMID:160731", "title": "Comparison of patch test results in two adjacent areas of England-I. (Industrial allergens).", "content": "A 3-year study of patch test reactions to the Standard European Battery has been carried out in two adjacent areas of S. E. England with the same climatic and cultural background. The source of materials and method of testing were identical; both observers had worked together in the same Contact Dermatitis department and the interpretation of reactions can therefore be considered to be consistent. The main differences between the two areas lay in the pattern of employment and of local medicament prescribing. The first only is examined here. One area was dominated by the automobile industry, the other by the furniture industry, with important subsidiary rubber, foam and electronics factories. The pattern that emerges shows that patch test reactions to the Standard European Battery were more likely to be related to environmental allergens and medicament usage than to industrial hazards. Chrome dermatitis was less common than elsewhere in Europe but nickel sensitivity showed the same pattern. Rubber chemical sensitivity reflected industrial, as well as domestic usage. Colophony and formaldehyde appeared to have less industrial significance than we expected. Special additional industrial allergens are not considered here but were of particular importance in the furniture industry. Although the numbers analysed were relatively small, we believe that they reflect the pattern to be expected in areas of relatively low industrial risk in Great Britain at the present time.", "contents": "Comparison of patch test results in two adjacent areas of England-I. (Industrial allergens). A 3-year study of patch test reactions to the Standard European Battery has been carried out in two adjacent areas of S. E. England with the same climatic and cultural background. The source of materials and method of testing were identical; both observers had worked together in the same Contact Dermatitis department and the interpretation of reactions can therefore be considered to be consistent. The main differences between the two areas lay in the pattern of employment and of local medicament prescribing. The first only is examined here. One area was dominated by the automobile industry, the other by the furniture industry, with important subsidiary rubber, foam and electronics factories. The pattern that emerges shows that patch test reactions to the Standard European Battery were more likely to be related to environmental allergens and medicament usage than to industrial hazards. Chrome dermatitis was less common than elsewhere in Europe but nickel sensitivity showed the same pattern. Rubber chemical sensitivity reflected industrial, as well as domestic usage. Colophony and formaldehyde appeared to have less industrial significance than we expected. Special additional industrial allergens are not considered here but were of particular importance in the furniture industry. Although the numbers analysed were relatively small, we believe that they reflect the pattern to be expected in areas of relatively low industrial risk in Great Britain at the present time."} {"id": "PMID:160732", "title": "Rare allergens - hidden sources of allergens.", "content": "Acceleration of technical development results in growing difficulties to trace allergens. In this respect rare allergens as well as hidden sources of well-known allergens not infrequently cause persistence of allergic dermatitis. Examples are presented for di-ethyl-ester of maleic acid, hydroxylammoniumhydrochloride, N-methyl-p-aminophenol, 2-hydroxy-3-naphtoic acid o-aniside and N-acetoacetyl-benzylamide.", "contents": "Rare allergens - hidden sources of allergens. Acceleration of technical development results in growing difficulties to trace allergens. In this respect rare allergens as well as hidden sources of well-known allergens not infrequently cause persistence of allergic dermatitis. Examples are presented for di-ethyl-ester of maleic acid, hydroxylammoniumhydrochloride, N-methyl-p-aminophenol, 2-hydroxy-3-naphtoic acid o-aniside and N-acetoacetyl-benzylamide."} {"id": "PMID:160733", "title": "Carbon and carbonless copy paper.", "content": "Proven allergic contact dermatitis from carbon paper is an exceptional rarity; the reported causes are dyes and plasticisers. But carbon paper is gradually being replaced by pressure-sensitive or carbonless copy paper, particularly for business forms. The method depends on mechanical pressure or chemical transfer. For the latter, colour formers are held in microcapsules, which rupture under pressure, and released when they produce the colour. Some office workers have claimed that the handling of used carbonless papers are responsible for symptoms affecting the skin, eyes, and upper respiratory tract, as well as systemic symptoms including headaches, drowsiness and fatigue. Patch tests are negative. If the symptoms are attributable to carbonless paper it is suggested that the colour former solvents are most likely to be responsible.", "contents": "Carbon and carbonless copy paper. Proven allergic contact dermatitis from carbon paper is an exceptional rarity; the reported causes are dyes and plasticisers. But carbon paper is gradually being replaced by pressure-sensitive or carbonless copy paper, particularly for business forms. The method depends on mechanical pressure or chemical transfer. For the latter, colour formers are held in microcapsules, which rupture under pressure, and released when they produce the colour. Some office workers have claimed that the handling of used carbonless papers are responsible for symptoms affecting the skin, eyes, and upper respiratory tract, as well as systemic symptoms including headaches, drowsiness and fatigue. Patch tests are negative. If the symptoms are attributable to carbonless paper it is suggested that the colour former solvents are most likely to be responsible."} {"id": "PMID:160734", "title": "First epidemiological study of contact dermatitis in Spain - 1977. Spanish Contact Dermatitis Research Group.", "content": "The present work is the first epidemiological study carried out by the Spanish Contact Dermatitis Research Group during 1977. During this year 2806 patients were studied with patch test among 30873 dermatological patients. The 60-62% of the totality had reactivity to one or more patches. Four major groups of allergens were able to consider, following the incidence in their power of sensitize. First group with strong incidence include: Nickel, Chromate, Cobalt, T.M.T.D.,P.P.D.A., Mercapto mix., and Wood tars. Second and third groups with medium incidence contain: Caines, Carbonates, Neomycin, Balsam of Peru, Mercury, Lanolin, Naphtyl mix., Formaldehyde, Benzalkonium chloride, P. P. D. A. mix, and Turpentine. Four group show very low incidence substances, as: Epoxi, Sulfonamides, Etilendiamine, Parabens, Chinoform, Colophony and Cinnamon oil. Few comments about age and occupations are included.", "contents": "First epidemiological study of contact dermatitis in Spain - 1977. Spanish Contact Dermatitis Research Group. The present work is the first epidemiological study carried out by the Spanish Contact Dermatitis Research Group during 1977. During this year 2806 patients were studied with patch test among 30873 dermatological patients. The 60-62% of the totality had reactivity to one or more patches. Four major groups of allergens were able to consider, following the incidence in their power of sensitize. First group with strong incidence include: Nickel, Chromate, Cobalt, T.M.T.D.,P.P.D.A., Mercapto mix., and Wood tars. Second and third groups with medium incidence contain: Caines, Carbonates, Neomycin, Balsam of Peru, Mercury, Lanolin, Naphtyl mix., Formaldehyde, Benzalkonium chloride, P. P. D. A. mix, and Turpentine. Four group show very low incidence substances, as: Epoxi, Sulfonamides, Etilendiamine, Parabens, Chinoform, Colophony and Cinnamon oil. Few comments about age and occupations are included."} {"id": "PMID:160735", "title": "Hand dermatitis in haridressers.", "content": "Most junior hairdressers, while shampooing, develop a dry irritant dermatitis over the metacarpophalangeal joints. It responds to simple treatment and disappears when the shampooing stage is passed. A few hairdressers develop eczema of the fingers: the response to treatment is less predictable and the prognosis is worse. In those who give up hairdressing the eczema generally improves or heals, in those who continue hairdressing the eczema is likely to persist, especially in atopics.", "contents": "Hand dermatitis in haridressers. Most junior hairdressers, while shampooing, develop a dry irritant dermatitis over the metacarpophalangeal joints. It responds to simple treatment and disappears when the shampooing stage is passed. A few hairdressers develop eczema of the fingers: the response to treatment is less predictable and the prognosis is worse. In those who give up hairdressing the eczema generally improves or heals, in those who continue hairdressing the eczema is likely to persist, especially in atopics."} {"id": "PMID:160736", "title": "Batch-consciousness in dermatologic management.", "content": "The chemical ingredients can vary between batches of industrial products. That means that the sensitizing capacity is also variable. This should be considered in taking histories, performing patch testing and analyzing chemicals.", "contents": "Batch-consciousness in dermatologic management. The chemical ingredients can vary between batches of industrial products. That means that the sensitizing capacity is also variable. This should be considered in taking histories, performing patch testing and analyzing chemicals."} {"id": "PMID:160737", "title": "Cross-sensitivity within the neomycin group of antibiotics.", "content": "Neomycin sensitive patients were tested for hypersensitivity to kanamycin, gentamycin, tobramycin, spectinomycin and to the new, not yet registered sisomycin and netilmicin. Cross-sensitivity occured in a considerable part of the patients, except for spectinomycin, the structure of which is basically different from that of the other aminoglycosides tested. The common occurence of cross-sensitivity between neomycin and other aminoglycoside antibiotics shows that it is possible to predict cross-sensitivity between a new drug and an old sensitizing one before clinical reactions from the new drug have occured. Such an investigation should be performed before adopting new antibiotics.", "contents": "Cross-sensitivity within the neomycin group of antibiotics. Neomycin sensitive patients were tested for hypersensitivity to kanamycin, gentamycin, tobramycin, spectinomycin and to the new, not yet registered sisomycin and netilmicin. Cross-sensitivity occured in a considerable part of the patients, except for spectinomycin, the structure of which is basically different from that of the other aminoglycosides tested. The common occurence of cross-sensitivity between neomycin and other aminoglycoside antibiotics shows that it is possible to predict cross-sensitivity between a new drug and an old sensitizing one before clinical reactions from the new drug have occured. Such an investigation should be performed before adopting new antibiotics."} {"id": "PMID:160738", "title": "Factors affecting the histochemical composition of reinnervated soleus muscle of rat.", "content": "The myofibrillar ATPase reaction was utilized to determine the relative proportion of type II fibres in reinnervated soleus muscle 6 months after transection and reunion of the nerve at various distances from the muscle. In self-reinnervated soleus muscle, a highly significant decrease in the percentage of type II fibres from 10.5 +/- 1.6% in normal muscle to 0.7 +/- 0.4% was noted. In randomly reinnervated soleus muscle the percentage of type II fibres gradually increased with the distance of the site of nerve transection from the muscle. After transection and reunion of the muscular branch of the tibial nerve, the type II fibres constituted 34.0 +/- 1.5% and that of the reinnervated soleus muscle after transection and reunion of the sciatic nerve stump was 73.7 +/- 1.7% of the total fibre population. Different factors which might be responsible for the observed differences in the degree of cytochemical transformation of muscle fibre types in the process of reinnervation are discussed.", "contents": "Factors affecting the histochemical composition of reinnervated soleus muscle of rat. The myofibrillar ATPase reaction was utilized to determine the relative proportion of type II fibres in reinnervated soleus muscle 6 months after transection and reunion of the nerve at various distances from the muscle. In self-reinnervated soleus muscle, a highly significant decrease in the percentage of type II fibres from 10.5 +/- 1.6% in normal muscle to 0.7 +/- 0.4% was noted. In randomly reinnervated soleus muscle the percentage of type II fibres gradually increased with the distance of the site of nerve transection from the muscle. After transection and reunion of the muscular branch of the tibial nerve, the type II fibres constituted 34.0 +/- 1.5% and that of the reinnervated soleus muscle after transection and reunion of the sciatic nerve stump was 73.7 +/- 1.7% of the total fibre population. Different factors which might be responsible for the observed differences in the degree of cytochemical transformation of muscle fibre types in the process of reinnervation are discussed."} {"id": "PMID:160739", "title": "Nerve elements of the heart in aorto-coronary by-pass conditions.", "content": "Experiments were conducted on 100 dogs with creation of autovenous aortocoronary shunts in the coronary artery. The hearts were examined 1 year following surgery by routine histological, neurohistological, histochemical and electron-microscopic techniques. No severe destructive changes were revealed in the shunting system. The main process develop in the heart very early following surgery and consist in reactive changes in the intramural nerve elements, elevation of the phosphatase activity in the walls of the microcirculatory bed, redistribution of acid and neutral mucopolysaccharides and changes of permeability of the haematohistiocytic barriers; they are an adaptation response of the myocardium to operative stress and new conditions of influx of blood to the cardiac muscle.", "contents": "Nerve elements of the heart in aorto-coronary by-pass conditions. Experiments were conducted on 100 dogs with creation of autovenous aortocoronary shunts in the coronary artery. The hearts were examined 1 year following surgery by routine histological, neurohistological, histochemical and electron-microscopic techniques. No severe destructive changes were revealed in the shunting system. The main process develop in the heart very early following surgery and consist in reactive changes in the intramural nerve elements, elevation of the phosphatase activity in the walls of the microcirculatory bed, redistribution of acid and neutral mucopolysaccharides and changes of permeability of the haematohistiocytic barriers; they are an adaptation response of the myocardium to operative stress and new conditions of influx of blood to the cardiac muscle."} {"id": "PMID:160740", "title": "Clinical features of multiple sclerosis in north-east Scotland.", "content": "The clinical features of multiple sclerosis (MS) in north-east Scotland have been examined along with an epidemiological study to determine the prevalence of the disease on 1st December, 1970. Patient information was collected from all available diagnostic indices, both retrospectively and prospectively from 1965. Every family doctor in the region contributed. The age and sex specific prevalence rates for MS in north-east Scotland on 1st December, 1970, are the highest ever recorded. Among the 80,000 women aged 40 to 69, one in every 340 had the disease. The mean incidence rate for a 12-year period was 5.0/100,000. A significantly better prognosis with regard to disability was found for onset with sensory symptoms, a relapsing/remitting type of course, men with long disease duration, and an initial remission period of 4 or more years. The occurrence of various abnormal neurological signs and symptoms has rarely been recorded in a large epidemiological study. The findings in this study, however, are similar to previous non-epidemiological studies.", "contents": "Clinical features of multiple sclerosis in north-east Scotland. The clinical features of multiple sclerosis (MS) in north-east Scotland have been examined along with an epidemiological study to determine the prevalence of the disease on 1st December, 1970. Patient information was collected from all available diagnostic indices, both retrospectively and prospectively from 1965. Every family doctor in the region contributed. The age and sex specific prevalence rates for MS in north-east Scotland on 1st December, 1970, are the highest ever recorded. Among the 80,000 women aged 40 to 69, one in every 340 had the disease. The mean incidence rate for a 12-year period was 5.0/100,000. A significantly better prognosis with regard to disability was found for onset with sensory symptoms, a relapsing/remitting type of course, men with long disease duration, and an initial remission period of 4 or more years. The occurrence of various abnormal neurological signs and symptoms has rarely been recorded in a large epidemiological study. The findings in this study, however, are similar to previous non-epidemiological studies."} {"id": "PMID:160741", "title": "The development and evaluation of an ovulation inhibitor (DIAne) containing an antiandrogen.", "content": "The combination of 2 mg cyproterone acetate, a pronounced antiandrogenic substance, in combination with 0.05 mg ethinyl estradiol has undergone intensive multiphasic clinical evaluation. The preparation with the trade name Diane has proven to be not only a reliable contraceptive, but also a very potent drug for the treatment of both acne and seborrhea, and of milder cases of hirsutism. The effect of Diane on markedly increased hair growth was not so pronounced. In addition to the presentation of the most pertinent steps of the clinical investigation of Diane, the possible mode of actions of antiandrogens alone and in combination with an estrogen is discussed.", "contents": "The development and evaluation of an ovulation inhibitor (DIAne) containing an antiandrogen. The combination of 2 mg cyproterone acetate, a pronounced antiandrogenic substance, in combination with 0.05 mg ethinyl estradiol has undergone intensive multiphasic clinical evaluation. The preparation with the trade name Diane has proven to be not only a reliable contraceptive, but also a very potent drug for the treatment of both acne and seborrhea, and of milder cases of hirsutism. The effect of Diane on markedly increased hair growth was not so pronounced. In addition to the presentation of the most pertinent steps of the clinical investigation of Diane, the possible mode of actions of antiandrogens alone and in combination with an estrogen is discussed."} {"id": "PMID:160742", "title": "Serum testosterone, FSH/LH and urinary excretion of estrogens and corticoids during treatment with an injectable, longacting estrogen-DHEA preparation.", "content": "Ten weeks after total hysterectomy and bilateral salpingo-oophorectomy, nine women were treated with injections of Gynodian, composed of 4 mg estradiol valerate and 200 mg dehydroepiandrosterone enanthate, followed by injections of Primodian, composed of 4 mg estradiol valerate and 90.27 mg testosterone enanthate. Before commencement of treatment estimation of serum FSH, LH and testosterone, and analyses for total estrogen, 17-ketogenic steroids and fractionated 17-ketosteroids in 24-hour urine samples were carried out in all patients. The same serum and urine analyses were made 2 weeks after the first Gynodian injection and the first Primodian injection respectively. Serum testosterone concentrations did not change during treatment with Gynodian, whereas they rose markedly after administration of Primodian. Two weeks after the first injection of Gynodian and also of Primodian, the total estrogen excretion was only slightly increased in comparison with the value measured before start of treatment, and the serum FSH/LH ratio was only slightly depressed. The daily urinary excretion of 17-ketogenic steroids and of fractionated 17-ketosteroids were unchanged during treatment.", "contents": "Serum testosterone, FSH/LH and urinary excretion of estrogens and corticoids during treatment with an injectable, longacting estrogen-DHEA preparation. Ten weeks after total hysterectomy and bilateral salpingo-oophorectomy, nine women were treated with injections of Gynodian, composed of 4 mg estradiol valerate and 200 mg dehydroepiandrosterone enanthate, followed by injections of Primodian, composed of 4 mg estradiol valerate and 90.27 mg testosterone enanthate. Before commencement of treatment estimation of serum FSH, LH and testosterone, and analyses for total estrogen, 17-ketogenic steroids and fractionated 17-ketosteroids in 24-hour urine samples were carried out in all patients. The same serum and urine analyses were made 2 weeks after the first Gynodian injection and the first Primodian injection respectively. Serum testosterone concentrations did not change during treatment with Gynodian, whereas they rose markedly after administration of Primodian. Two weeks after the first injection of Gynodian and also of Primodian, the total estrogen excretion was only slightly increased in comparison with the value measured before start of treatment, and the serum FSH/LH ratio was only slightly depressed. The daily urinary excretion of 17-ketogenic steroids and of fractionated 17-ketosteroids were unchanged during treatment."} {"id": "PMID:160743", "title": "Morphological, histochemical and X-ray microanalytical examination of deposits on soft contact lenses in extended wearing.", "content": "The deposits on 29 contact lenses of various water content from 20 wearers were analysed by the methods given in the title. Six lenses were used as bandage lenses, the remaining for optical correction. The age of the patients varied from 7 to 56 years, two-thirds being under 45 years. Wearing time had been from 1 week to 1 year, with an average of 13 weeks. The results obtained by the methods applied showed that calcium was present in just over two-thirds of the cases (20/29), other elements being infrequent. Mucopolysaccharides were found in just under two-thirds (18/29). Chlorine was present in one-fifth of the cases. No significant amounts of lipid were detected. Fungi were found in three cases (3/29). Bacteria were also found in these cases, but never without fungi. Evaluation of the methods applied showed that the methods of choice were macroscopical examination and scanning microscopy in combination with X-ray microanalysis, in a few cases combined with histochemistry. None of the methods applied is sufficient for protein analysis.", "contents": "Morphological, histochemical and X-ray microanalytical examination of deposits on soft contact lenses in extended wearing. The deposits on 29 contact lenses of various water content from 20 wearers were analysed by the methods given in the title. Six lenses were used as bandage lenses, the remaining for optical correction. The age of the patients varied from 7 to 56 years, two-thirds being under 45 years. Wearing time had been from 1 week to 1 year, with an average of 13 weeks. The results obtained by the methods applied showed that calcium was present in just over two-thirds of the cases (20/29), other elements being infrequent. Mucopolysaccharides were found in just under two-thirds (18/29). Chlorine was present in one-fifth of the cases. No significant amounts of lipid were detected. Fungi were found in three cases (3/29). Bacteria were also found in these cases, but never without fungi. Evaluation of the methods applied showed that the methods of choice were macroscopical examination and scanning microscopy in combination with X-ray microanalysis, in a few cases combined with histochemistry. None of the methods applied is sufficient for protein analysis."} {"id": "PMID:160744", "title": "Performance of the hypertrophied left ventricle in spontaneously hypertensive rat. Effects of changes in preload and afterload.", "content": "Isolated hearts from adult spontaneously hypertensive rats (SHR; Okamoto 1969), with established hypertension, were investigated in an antegrade perfusion apparatus where preload and afterload could be varied independently. Frank-Starling curves were constructed at constant afterloads ranging from 50 mmHg to 150 mmHg. As earlier reported, the SHR hearts exhibited a rightward shift of their Frank-Startling relationships compared to those from the normotensive control hearts, though visible only at afterloads up to about 100 mmHg. At higher afterloads the SHR hearts performed significantly better then the NCR ones as their maximal stroke volume was significantly greater compared to that of controls. Thus, left ventricular hypertrophy obviously increases the work capacity of the heart, though at the cost of an altered Frank-Startling relation dependent on the reduced diastolic compliance. For such reasons the myocardial hypertrophy in established SHR hypertension must be considered a physiologic adaptation and not a degenerative phenomenon, though naturally degenerative processes may later become superimposed.", "contents": "Performance of the hypertrophied left ventricle in spontaneously hypertensive rat. Effects of changes in preload and afterload. Isolated hearts from adult spontaneously hypertensive rats (SHR; Okamoto 1969), with established hypertension, were investigated in an antegrade perfusion apparatus where preload and afterload could be varied independently. Frank-Starling curves were constructed at constant afterloads ranging from 50 mmHg to 150 mmHg. As earlier reported, the SHR hearts exhibited a rightward shift of their Frank-Startling relationships compared to those from the normotensive control hearts, though visible only at afterloads up to about 100 mmHg. At higher afterloads the SHR hearts performed significantly better then the NCR ones as their maximal stroke volume was significantly greater compared to that of controls. Thus, left ventricular hypertrophy obviously increases the work capacity of the heart, though at the cost of an altered Frank-Startling relation dependent on the reduced diastolic compliance. For such reasons the myocardial hypertrophy in established SHR hypertension must be considered a physiologic adaptation and not a degenerative phenomenon, though naturally degenerative processes may later become superimposed."} {"id": "PMID:160745", "title": "Human plantar flexion strength and structure.", "content": "Plantar flexion strengths were studied in 30 right-handed males. Static and dynamic maximum plantar flexion torques were recorded, knees fully extended (0 degrees) and in 90 degrees flexion. In five of the subjects the soleus and gastrocnemius muscle structure were studied by light microscopy and enzyme histochemistry. Specimens were obtained by needle biopsy, usually bilaterally. Intraindividual declines of force were found to be a function of angular motion velocity. Static and dynamic torques correlated significantly. Peak torques were significantly greater (mean 15%) at the 0 degrees than at the 90 degrees knee angle and left maximum plantar flexion torques at 0 degrees were greater (mean 10%) than right. Mean morphometric data on the m. soleus suggested right-left symmetry, which could not be demonstrated for the m. gastrocnemius. Fibres with low stainability for myofibrillar ATPase (Type 1 fibres) had smaller diameters, but constituted the major part of the cross-sectional areas. In these five non-athletes no significant correlation between data on plantar flexion strength and morphometric data on triceps surae structure could be demonstrated. On the other hand, strength covariated with calf circumference.", "contents": "Human plantar flexion strength and structure. Plantar flexion strengths were studied in 30 right-handed males. Static and dynamic maximum plantar flexion torques were recorded, knees fully extended (0 degrees) and in 90 degrees flexion. In five of the subjects the soleus and gastrocnemius muscle structure were studied by light microscopy and enzyme histochemistry. Specimens were obtained by needle biopsy, usually bilaterally. Intraindividual declines of force were found to be a function of angular motion velocity. Static and dynamic torques correlated significantly. Peak torques were significantly greater (mean 15%) at the 0 degrees than at the 90 degrees knee angle and left maximum plantar flexion torques at 0 degrees were greater (mean 10%) than right. Mean morphometric data on the m. soleus suggested right-left symmetry, which could not be demonstrated for the m. gastrocnemius. Fibres with low stainability for myofibrillar ATPase (Type 1 fibres) had smaller diameters, but constituted the major part of the cross-sectional areas. In these five non-athletes no significant correlation between data on plantar flexion strength and morphometric data on triceps surae structure could be demonstrated. On the other hand, strength covariated with calf circumference."} {"id": "PMID:160746", "title": "Left atrial pressure in normotensive and spontaneously hypertensive rats.", "content": "The left atrial pressure in adult spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control rat (NCR) was measured via chronically implanted catheters. In SHR left atrial pressure in end-expiration was more than twice as high (10.3 +/- 0.4 mmHg) as in NCR (4.6 +/- 0.3 mmHg). There was no difference in the intrapleural pressure between the two groups of rats, therefore the enhanced left atrial pressure in SHR represents a real rise in the diastolic filling pressure of its left ventricle. This is considered to be the most important compensation for the earlier reported rightward shift of the Frank-Starling curve in SHR (Hallb\u00e4ck, Isaksson & Noresson 1975, Noresson et al. 1979a). Without this compensation the stroke volume would have been drastically reduced for the hypertrophied heart.", "contents": "Left atrial pressure in normotensive and spontaneously hypertensive rats. The left atrial pressure in adult spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control rat (NCR) was measured via chronically implanted catheters. In SHR left atrial pressure in end-expiration was more than twice as high (10.3 +/- 0.4 mmHg) as in NCR (4.6 +/- 0.3 mmHg). There was no difference in the intrapleural pressure between the two groups of rats, therefore the enhanced left atrial pressure in SHR represents a real rise in the diastolic filling pressure of its left ventricle. This is considered to be the most important compensation for the earlier reported rightward shift of the Frank-Starling curve in SHR (Hallb\u00e4ck, Isaksson & Noresson 1975, Noresson et al. 1979a). Without this compensation the stroke volume would have been drastically reduced for the hypertrophied heart."} {"id": "PMID:160747", "title": "Determination of blood flow through arteriovenous fistulae and shunts.", "content": "A videodensitometric method for estimating relative flow was employed in a patient with a bovine arteriovenous fistula. Analogous arteriovenous communications of different sizes were created in two dogs for comparison. Local and general hemodynamic parameters were measured. The videodensitometric method proved to be highly accurate compared to electromagnetic flow readings and is the method of choice in estimating shunt flow in connection with routine angiography.", "contents": "Determination of blood flow through arteriovenous fistulae and shunts. A videodensitometric method for estimating relative flow was employed in a patient with a bovine arteriovenous fistula. Analogous arteriovenous communications of different sizes were created in two dogs for comparison. Local and general hemodynamic parameters were measured. The videodensitometric method proved to be highly accurate compared to electromagnetic flow readings and is the method of choice in estimating shunt flow in connection with routine angiography."} {"id": "PMID:160748", "title": "Rheumatoid arthritis, immune complex disease, and hypereosinophilic syndrome. Report on a case.", "content": "A patient with typical rheumatoid arthritis is presented. After a short period of the disease a hyperosinophilic syndrome (HES) developed with vasculitis, pulmonary fibrosis, and thrombosis, and the disease took a malignant course. The patient died within a year after the diagnosis of HES. High titres of rheumatoid factor were manifested and total complement (CH50) was very low, indicating an active immune disease. As HES has been suggested to have an autoimmune aetiology, these findings are interesting, as positive rheumatoid serology has very rarely been reported in patients with this syndrome.", "contents": "Rheumatoid arthritis, immune complex disease, and hypereosinophilic syndrome. Report on a case. A patient with typical rheumatoid arthritis is presented. After a short period of the disease a hyperosinophilic syndrome (HES) developed with vasculitis, pulmonary fibrosis, and thrombosis, and the disease took a malignant course. The patient died within a year after the diagnosis of HES. High titres of rheumatoid factor were manifested and total complement (CH50) was very low, indicating an active immune disease. As HES has been suggested to have an autoimmune aetiology, these findings are interesting, as positive rheumatoid serology has very rarely been reported in patients with this syndrome."} {"id": "PMID:160753", "title": "Differences in regional capillary distribution and myocyte sizes in normal and hypertrophic rat hearts.", "content": "Data are reported which show significant regional capillary differences in left ventricular endocardium and epicardium of normal rats and of rats with hyperthyroid-induced cardiac hypertrophy. The epicardial region of control rats has 38% more capillaries than the endocardial region. Control endocardial myocytes are 62% larger in cross-sectional area than epicardial myocytes. Hypertrophic hearts exhibit regional differences in capillary density similar to those in the normal hearts, but there is an overall reduction of 12 and 17.5% in capillary density in both regions. The average cross-sectional area of myocytes increases 34.5% in the epicardium and 22.5% in the endocardium.", "contents": "Differences in regional capillary distribution and myocyte sizes in normal and hypertrophic rat hearts. Data are reported which show significant regional capillary differences in left ventricular endocardium and epicardium of normal rats and of rats with hyperthyroid-induced cardiac hypertrophy. The epicardial region of control rats has 38% more capillaries than the endocardial region. Control endocardial myocytes are 62% larger in cross-sectional area than epicardial myocytes. Hypertrophic hearts exhibit regional differences in capillary density similar to those in the normal hearts, but there is an overall reduction of 12 and 17.5% in capillary density in both regions. The average cross-sectional area of myocytes increases 34.5% in the epicardium and 22.5% in the endocardium."} {"id": "PMID:160754", "title": "Lymphocyte surface markers and serum immunoglobulins in persons with Down's syndrome.", "content": "Distributions of the serum immunoglobulins, of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. Noninstitutionalized Down's syndrome children, who were 2 to 6 years of age, had lower serum IgM levels, lower total white blood cell counts, lower total lymphocytes, lower B lymphocytes, and lower IgM- and IgA-producing lymphocytes than did retarded controls. Institutionalized Down's syndrome adults, 17 to 51 years of age, had significantly higher serum IgG and IgA levels than did retarded controls. Their total lymphocytes, B lymphocytes, and IgM-producing lymphocytes were in the same direction as in the Down's syndrome children but were of borderline statistical significance (between p = .09 and .11). T lymphocytes were not significantly lower for any of the Down's syndrome-retarded groups than those for controls, but the trend was in that direction.", "contents": "Lymphocyte surface markers and serum immunoglobulins in persons with Down's syndrome. Distributions of the serum immunoglobulins, of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. Noninstitutionalized Down's syndrome children, who were 2 to 6 years of age, had lower serum IgM levels, lower total white blood cell counts, lower total lymphocytes, lower B lymphocytes, and lower IgM- and IgA-producing lymphocytes than did retarded controls. Institutionalized Down's syndrome adults, 17 to 51 years of age, had significantly higher serum IgG and IgA levels than did retarded controls. Their total lymphocytes, B lymphocytes, and IgM-producing lymphocytes were in the same direction as in the Down's syndrome children but were of borderline statistical significance (between p = .09 and .11). T lymphocytes were not significantly lower for any of the Down's syndrome-retarded groups than those for controls, but the trend was in that direction."} {"id": "PMID:160755", "title": "Communicative and sensorimotor development of Down's syndrome children.", "content": "Imperative and declarative performative behavior was examined in nonretarded and Down's syndrome children operating at two stages of sensorimotor intelligence. In both groups, more advanced types of performative behavior generally associated with a higher sensorimotor stage. Relative to the nonretarded children of the same sensorimotor stages, the Down's syndrome children relied more heavily on gestures in their imperative and declarative usage. Evidence was also obtained suggesting that the correspondence between sensorimotor stage and performative behavior is closer at younger ages than at older ages.", "contents": "Communicative and sensorimotor development of Down's syndrome children. Imperative and declarative performative behavior was examined in nonretarded and Down's syndrome children operating at two stages of sensorimotor intelligence. In both groups, more advanced types of performative behavior generally associated with a higher sensorimotor stage. Relative to the nonretarded children of the same sensorimotor stages, the Down's syndrome children relied more heavily on gestures in their imperative and declarative usage. Evidence was also obtained suggesting that the correspondence between sensorimotor stage and performative behavior is closer at younger ages than at older ages."} {"id": "PMID:160756", "title": "Mg2+-dependent adenosine triphosphatase as an enzyme histochemical marker for the lymphomas of B-cell origin.", "content": "Twenty-nine cases of malignant lymphoma were studied by the enzyme histochemical method and membrane surface markers. Strong adenosine triphosphatase (ATPase) activity was demonstrated in 15 cases of 20 B lymphomas and in one case of null-cell lymphoma (1/1) by a light- and electron-microscopic enzyme histochemical method according to Wachstein et al. Neoplastic cells in nodules of 2 nodular lymphomas (0/2) and in 8 cases of T lymphomas (0/8) did not show any ATPase activity enzyme-histochemically. The ATPase activity of B lymphomas was electron-microscopically demonstrated on the plasma membrane of lymphoma cells but not in the cytoplasmic organelles. The specificity of ATPase activity in B lymphomas was also examined enzyme-histochemically with reference to normal lymphoid tissues. Such specificity was similar to that of non-neoplastic B lymphocytes of primary follicles and the mantle zone of secondary follicles in lymphoid tissues. Therefore, ATPase is one of the useful enzyme histochemical markers in differentiating T and B subclasses of malignant lymphomas.", "contents": "Mg2+-dependent adenosine triphosphatase as an enzyme histochemical marker for the lymphomas of B-cell origin. Twenty-nine cases of malignant lymphoma were studied by the enzyme histochemical method and membrane surface markers. Strong adenosine triphosphatase (ATPase) activity was demonstrated in 15 cases of 20 B lymphomas and in one case of null-cell lymphoma (1/1) by a light- and electron-microscopic enzyme histochemical method according to Wachstein et al. Neoplastic cells in nodules of 2 nodular lymphomas (0/2) and in 8 cases of T lymphomas (0/8) did not show any ATPase activity enzyme-histochemically. The ATPase activity of B lymphomas was electron-microscopically demonstrated on the plasma membrane of lymphoma cells but not in the cytoplasmic organelles. The specificity of ATPase activity in B lymphomas was also examined enzyme-histochemically with reference to normal lymphoid tissues. Such specificity was similar to that of non-neoplastic B lymphocytes of primary follicles and the mantle zone of secondary follicles in lymphoid tissues. Therefore, ATPase is one of the useful enzyme histochemical markers in differentiating T and B subclasses of malignant lymphomas."} {"id": "PMID:160757", "title": "The treatment of chronic back pain. A preliminary survey of the effect of radiofrequency denervation of the posterior vertebral joints.", "content": "Structures innervated by the dorsal primary ramus play a significant part in the genesis of chronic backache and associated leg pain. The features of this syndrome are described and compared with those in the more familiar clinical picture following intervertebral disc degeneration. However these clinical entities are seldom entirely separate and the diagnosis is often also complicated by psychosomatic factors and the consequences of previous back surgery. A technique of percutaneous facet denervation with a radiofrequency probe, although by no means successful in every case, is entirely safe and a very wothwhile procedure. It has helped many patients, who would otherwise have been disabled by pain and restricted in their activities.", "contents": "The treatment of chronic back pain. A preliminary survey of the effect of radiofrequency denervation of the posterior vertebral joints. Structures innervated by the dorsal primary ramus play a significant part in the genesis of chronic backache and associated leg pain. The features of this syndrome are described and compared with those in the more familiar clinical picture following intervertebral disc degeneration. However these clinical entities are seldom entirely separate and the diagnosis is often also complicated by psychosomatic factors and the consequences of previous back surgery. A technique of percutaneous facet denervation with a radiofrequency probe, although by no means successful in every case, is entirely safe and a very wothwhile procedure. It has helped many patients, who would otherwise have been disabled by pain and restricted in their activities."} {"id": "PMID:160758", "title": "Burma revisited.", "content": "The author, who had spent a year with a mobile field hospital in Burma in 1944 during World War II, was able to visit Rangoon for 5 days in 1977 with the assistance of a grant from the Association of Anaesthetists of Great Britain and Ireland. Some impressions of life in Burma today are given, especially in relation to the problem of providing an anaesthetic service for the main hospitals in Rangoon and the work of Professor Win Maung, FFARCS and his University department. The author also describes some of the aid which it has been possible to organise since his return to the United Kingdom and outlines requirements for the future.", "contents": "Burma revisited. The author, who had spent a year with a mobile field hospital in Burma in 1944 during World War II, was able to visit Rangoon for 5 days in 1977 with the assistance of a grant from the Association of Anaesthetists of Great Britain and Ireland. Some impressions of life in Burma today are given, especially in relation to the problem of providing an anaesthetic service for the main hospitals in Rangoon and the work of Professor Win Maung, FFARCS and his University department. The author also describes some of the aid which it has been possible to organise since his return to the United Kingdom and outlines requirements for the future."} {"id": "PMID:160761", "title": "Muscle spindle supply to the masticatory muscles in the Japane ermine (Carnivora).", "content": "Histological examination of the jaw muscles of the Japanese ermine showed that 4 jaw-closing muscles have 13 muscle spindles on one side of the face. The temporal muscle has 99 muscle spindles, 68 being in the anterior vertical and 31 in the posterior horizontal belly. The masseter muscle has 33 muscle spindles, 23 being in the profound and 10 in the superficial belly. The medial pterygoid muscle has 7 muscle spindles and the zygomaticomandibular muscle contains 4 muscle spindles. The lateral pterygoid and the jaw-opening muscles have no spindles.", "contents": "Muscle spindle supply to the masticatory muscles in the Japane ermine (Carnivora). Histological examination of the jaw muscles of the Japanese ermine showed that 4 jaw-closing muscles have 13 muscle spindles on one side of the face. The temporal muscle has 99 muscle spindles, 68 being in the anterior vertical and 31 in the posterior horizontal belly. The masseter muscle has 33 muscle spindles, 23 being in the profound and 10 in the superficial belly. The medial pterygoid muscle has 7 muscle spindles and the zygomaticomandibular muscle contains 4 muscle spindles. The lateral pterygoid and the jaw-opening muscles have no spindles."} {"id": "PMID:160762", "title": "Effects of tenotomy on the muscle of the turtle: a histochemical study.", "content": "Tenotomized turtle muscles exhibited some changes similar to those found in mammalian tenotomized muscles. These changes included presence of small rounded and angulated fibres with high oxidative reaction, acute necrosis of fibres with degenerative changes, perivascular cellular reaction, phagocytosis and the atrophy of all 3 types of fibres. In contrast to mammalian tenotomized muscles, no decrease in PAS positive material and phosphorylase activity was noticeable. Also, the central core fibres and nemaline rods were absent in tenotomized turtle muscles.", "contents": "Effects of tenotomy on the muscle of the turtle: a histochemical study. Tenotomized turtle muscles exhibited some changes similar to those found in mammalian tenotomized muscles. These changes included presence of small rounded and angulated fibres with high oxidative reaction, acute necrosis of fibres with degenerative changes, perivascular cellular reaction, phagocytosis and the atrophy of all 3 types of fibres. In contrast to mammalian tenotomized muscles, no decrease in PAS positive material and phosphorylase activity was noticeable. Also, the central core fibres and nemaline rods were absent in tenotomized turtle muscles."} {"id": "PMID:160763", "title": "Effect of pyrantel tartrate and carbadox on acquisition of the swine kidneyworm (Stephanurus dentatus) and other parasites by pigs on contaminated lots.", "content": "A combination of pyrantel tartrate (106 mg/kg of body weight) and carbadox (55 mg/kg of body weight) in ground feed was fed to 20 weaned pigs (av wt, 14.4 kg) for 42 days. Another group of 20 pigs included nontreated controls. The pigs were farrowed and suckled in a slat-floored farrowing house and had minimal exposure to the small intestinal threadworm (Stronglyoides ransomi) until they were placed on severely contaminated dirt lots at the start of the experiment. Five pigs from each of the two groups were necropsied on day 42. Carbadox was withheld from the feed for the 15 remaining treated pigs. All other pigs were necropsied when they attained market weight, 72 to 83 days layer. Treated pigs killed at market weight had 44% fewer (P less than 0.10) kidneyworms (Stephanurus dentatus) than did control pigs. A 17% increase (P less than 0.01) in the weights of livers of control pigs when compared with treated market-weight pigs was associated with an increase of fibrotic hepatic tissue of control pigs. Worm infections were reduced in the treated market-weight pigs: by 96% (P less than 0.05) for the large roundworm (Ascaris suum), 77% (P less than 0.01) for nodular worms (Oesophagostomum spp), and 64% (P less than 0.01) for the intestinal threadworm. There was some evidence for prophylaxis in market-weight pigs (P less than 0.10) against lungworms (Metastrongylus spp), but none against the whipworm (Trichuris suis) or thick stomach worms (Ascarops strongylina and Physocephalus sexalatus). Pigs given the pyrantel tartrate in feed until attaining market weight maintained a feed-to-gain ratio superior (7.1%) to that of nontreated pigs.", "contents": "Effect of pyrantel tartrate and carbadox on acquisition of the swine kidneyworm (Stephanurus dentatus) and other parasites by pigs on contaminated lots. A combination of pyrantel tartrate (106 mg/kg of body weight) and carbadox (55 mg/kg of body weight) in ground feed was fed to 20 weaned pigs (av wt, 14.4 kg) for 42 days. Another group of 20 pigs included nontreated controls. The pigs were farrowed and suckled in a slat-floored farrowing house and had minimal exposure to the small intestinal threadworm (Stronglyoides ransomi) until they were placed on severely contaminated dirt lots at the start of the experiment. Five pigs from each of the two groups were necropsied on day 42. Carbadox was withheld from the feed for the 15 remaining treated pigs. All other pigs were necropsied when they attained market weight, 72 to 83 days layer. Treated pigs killed at market weight had 44% fewer (P less than 0.10) kidneyworms (Stephanurus dentatus) than did control pigs. A 17% increase (P less than 0.01) in the weights of livers of control pigs when compared with treated market-weight pigs was associated with an increase of fibrotic hepatic tissue of control pigs. Worm infections were reduced in the treated market-weight pigs: by 96% (P less than 0.05) for the large roundworm (Ascaris suum), 77% (P less than 0.01) for nodular worms (Oesophagostomum spp), and 64% (P less than 0.01) for the intestinal threadworm. There was some evidence for prophylaxis in market-weight pigs (P less than 0.10) against lungworms (Metastrongylus spp), but none against the whipworm (Trichuris suis) or thick stomach worms (Ascarops strongylina and Physocephalus sexalatus). Pigs given the pyrantel tartrate in feed until attaining market weight maintained a feed-to-gain ratio superior (7.1%) to that of nontreated pigs."} {"id": "PMID:160764", "title": "Effects of hormonal therapy on the microbiology of seborrheic dogs.", "content": "Quantitative and qualitative bacterial assays were performed on the skin of three dogs with endocrine-related primary metabolic seborrhea. After the dogs were treated (thyroid supplementation or castration, bacterial analyses were again performed on the same sites. Before therapy, the dogs had a cutaneous flora composed mainly of Staphylococcus aureus coagulase-positive organisms. After therapy, there was a significantly lower bacterial count, and two of the dogs had floras consisting mainly of coagulase-negative cocci. During the study, the two dogs that reverted bacteriologically to a normal cutaneous microenvironment became normal dermatologically. The third dog improved, but continued to have minor signs of seborrhea.", "contents": "Effects of hormonal therapy on the microbiology of seborrheic dogs. Quantitative and qualitative bacterial assays were performed on the skin of three dogs with endocrine-related primary metabolic seborrhea. After the dogs were treated (thyroid supplementation or castration, bacterial analyses were again performed on the same sites. Before therapy, the dogs had a cutaneous flora composed mainly of Staphylococcus aureus coagulase-positive organisms. After therapy, there was a significantly lower bacterial count, and two of the dogs had floras consisting mainly of coagulase-negative cocci. During the study, the two dogs that reverted bacteriologically to a normal cutaneous microenvironment became normal dermatologically. The third dog improved, but continued to have minor signs of seborrhea."} {"id": "PMID:160765", "title": "Identification and distribution of swine serum immunoglobins that react with Trichinella spiralis antigens and may interfere with the enzyme-labeled antibody test for trichinosis.", "content": "Sera from Trichinella spiralis digestion-negative swine contained variable amounts of two immunoglobins that reacted with T spiralis antigen in the indirect enzyme-labeled antibody test for trichinosis. One of these immunoglobins, detected by heavy chain-specific anti-swine immunoglobulin G (IgG) conjugate, was removed by absorption with T spiralis larvae. A second immunoglobin, detected by heavy chain-specific anti-swine IgM, was not removed by absorption with T spiralis larvae and increased in amount with the age of the animal. These two immunoglobins varied independently in individual animals and showed some specificity for the antigen; ie, they did not merely reflect changes in total serum IgG or IgM. In contrast to IgG anti-T spiralis antibody from experimentally infected animals, neither of these immunoglobins could be detected in double-diffusion tests against the antigen or by counter immunoelectrophoresis. Either of these immunoglobins could interfere with the indirect test for T spiralis antibodies, depending upon whether anti-swine IgG or IgM conjugate is used. The factors which initiate synthesis and control serum concentrations of these immunoglobins are not known.", "contents": "Identification and distribution of swine serum immunoglobins that react with Trichinella spiralis antigens and may interfere with the enzyme-labeled antibody test for trichinosis. Sera from Trichinella spiralis digestion-negative swine contained variable amounts of two immunoglobins that reacted with T spiralis antigen in the indirect enzyme-labeled antibody test for trichinosis. One of these immunoglobins, detected by heavy chain-specific anti-swine immunoglobulin G (IgG) conjugate, was removed by absorption with T spiralis larvae. A second immunoglobin, detected by heavy chain-specific anti-swine IgM, was not removed by absorption with T spiralis larvae and increased in amount with the age of the animal. These two immunoglobins varied independently in individual animals and showed some specificity for the antigen; ie, they did not merely reflect changes in total serum IgG or IgM. In contrast to IgG anti-T spiralis antibody from experimentally infected animals, neither of these immunoglobins could be detected in double-diffusion tests against the antigen or by counter immunoelectrophoresis. Either of these immunoglobins could interfere with the indirect test for T spiralis antibodies, depending upon whether anti-swine IgG or IgM conjugate is used. The factors which initiate synthesis and control serum concentrations of these immunoglobins are not known."} {"id": "PMID:160766", "title": "Calibration and use of electromagnetic flow transducers.", "content": "Electromagnetic flowmeters frequently are used to measure volumetric blood flow in vessels. An in vitro method of calibration, using a constant supply-pressure system, was studied. Potential problems encountered in acute and chronic applications are discussed. Using this calibration system, manufacturers' recommended calibration factors were not in agreement with actual flow calibration factors, and zero, as determined electrically, was not the same as that determined mechanically. Transducer sensitivity decreased with increasing concentrations of red blood cells but was not affected by fluid viscosity. Application problems of vessel constriction by the transducer, transducer orientation about the vessel, and chronic instrumentation are discussed.", "contents": "Calibration and use of electromagnetic flow transducers. Electromagnetic flowmeters frequently are used to measure volumetric blood flow in vessels. An in vitro method of calibration, using a constant supply-pressure system, was studied. Potential problems encountered in acute and chronic applications are discussed. Using this calibration system, manufacturers' recommended calibration factors were not in agreement with actual flow calibration factors, and zero, as determined electrically, was not the same as that determined mechanically. Transducer sensitivity decreased with increasing concentrations of red blood cells but was not affected by fluid viscosity. Application problems of vessel constriction by the transducer, transducer orientation about the vessel, and chronic instrumentation are discussed."} {"id": "PMID:160775", "title": "Abnormal fibrous protein isolated from the stratum corneum of a patient with bullous congenital ichthyosiform erythroderma (BCIE).", "content": "The fibrous protein of stratum corneum was isolated from a patient with bullous congenital ichthyosiform erythroderma (BCIE), and its properties characterized using electron microscopy, amino acid analysis and SDS gel electrophoresis. Results were compared with the characteristics of the fibrous protein isolated from stratum corneum of normal controls. From 900 mg (dry weight) of stratum corneum, 68 mg of fibrous protein was obtained from the patient, while 178 mg was obtained from the normal control. Structural differences were observed with electron microscopy and chemical differences, were shown in the ratio of several amino acids. On SDS electrophoresis, the 55,000 dalton constituent of normal fibrous protein could not be identified in the fibrous protein from this patient. These results suggest that an alteration of the polypeptide composition of fibrous protein from this patient with BCIE occurred, and this alteration induced the morphological and clinical features of this dominant genetic keratinization disorder.", "contents": "Abnormal fibrous protein isolated from the stratum corneum of a patient with bullous congenital ichthyosiform erythroderma (BCIE). The fibrous protein of stratum corneum was isolated from a patient with bullous congenital ichthyosiform erythroderma (BCIE), and its properties characterized using electron microscopy, amino acid analysis and SDS gel electrophoresis. Results were compared with the characteristics of the fibrous protein isolated from stratum corneum of normal controls. From 900 mg (dry weight) of stratum corneum, 68 mg of fibrous protein was obtained from the patient, while 178 mg was obtained from the normal control. Structural differences were observed with electron microscopy and chemical differences, were shown in the ratio of several amino acids. On SDS electrophoresis, the 55,000 dalton constituent of normal fibrous protein could not be identified in the fibrous protein from this patient. These results suggest that an alteration of the polypeptide composition of fibrous protein from this patient with BCIE occurred, and this alteration induced the morphological and clinical features of this dominant genetic keratinization disorder."} {"id": "PMID:160772", "title": "The effect of immunosuppressive therapy on the course of development of Dictyocaulus viviparus in guinea-pigs.", "content": "Three chemical immunosuppressive agents, viz. dexamethasone, methotrexate and cyclophosphamide, were administered to guinea-pigs two days prior to their infection with Dictyocaulus viviparus infective larvae and onward. The cell mediated immunity of these guinea-pigs was subdued under the influence of these immunosuppressive agents as evidenced by macrophage migration inhibition test but this could not prevent or postpone the rejection of majority of the worm population of guinea-pigs on day 15 post-infection. Methotrexate exerted, besides its cell mediated immunosuppressive action on the host, some inhibitory influence on the general biotic potentialities of the developing worms so that, on day eight post-infection, a reduced number of stunted worms was recovered.", "contents": "The effect of immunosuppressive therapy on the course of development of Dictyocaulus viviparus in guinea-pigs. Three chemical immunosuppressive agents, viz. dexamethasone, methotrexate and cyclophosphamide, were administered to guinea-pigs two days prior to their infection with Dictyocaulus viviparus infective larvae and onward. The cell mediated immunity of these guinea-pigs was subdued under the influence of these immunosuppressive agents as evidenced by macrophage migration inhibition test but this could not prevent or postpone the rejection of majority of the worm population of guinea-pigs on day 15 post-infection. Methotrexate exerted, besides its cell mediated immunosuppressive action on the host, some inhibitory influence on the general biotic potentialities of the developing worms so that, on day eight post-infection, a reduced number of stunted worms was recovered."} {"id": "PMID:160776", "title": "[Radioimmunoassay of dehydroepiandrosterone and 5-androstene-3-beta, 17-beta-diol in the plasma of psoriatics and controls].", "content": "In the plasma of psoriatics and controls the steroids dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol were determined by radioimmunoassay. Corresponding earlier findings obtained by photometric methods in psoriatics the plasma level of dehydroepiandrosterone is increased and that of androstenediol is decreased.", "contents": "[Radioimmunoassay of dehydroepiandrosterone and 5-androstene-3-beta, 17-beta-diol in the plasma of psoriatics and controls]. In the plasma of psoriatics and controls the steroids dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol were determined by radioimmunoassay. Corresponding earlier findings obtained by photometric methods in psoriatics the plasma level of dehydroepiandrosterone is increased and that of androstenediol is decreased."} {"id": "PMID:160777", "title": "Boundary layer separation in models of side-to-end arterial anastomoses.", "content": "We performed an investigation of boundary layer separation in models of side-to-end anastomoses, used clinically in axillofemoral and femorofemoral grafting. Boundary layer separation occurs when momentum causes a fluid to flow against a local pressure gradient. Models of side-to-end anastomoses were constructed from Dacron grafting material and from clear plastic blocks and tubing. Fluid energy loss across the anastomosis was small and physiologically insignificant. Local adverse pressure gradients were demonstrated near the anastomosis. Flow visualization studies demonstrated characteristic areas of boundary layer separation in the region of the adverse pressure gradients. The separation region involved both the main limb and the side arm. The separation forms a shell or ring of slow-moving fluid around the mainstream. Preliminary studies with pulsatile flow and with blood demonstrate that boundary layer separation occurs under clinical flow conditions. Boundary layer separation may play a role in the development of anastomotic hyperplasia and atherosclerotic deposits in the vicinity of surgical anastomoses.", "contents": "Boundary layer separation in models of side-to-end arterial anastomoses. We performed an investigation of boundary layer separation in models of side-to-end anastomoses, used clinically in axillofemoral and femorofemoral grafting. Boundary layer separation occurs when momentum causes a fluid to flow against a local pressure gradient. Models of side-to-end anastomoses were constructed from Dacron grafting material and from clear plastic blocks and tubing. Fluid energy loss across the anastomosis was small and physiologically insignificant. Local adverse pressure gradients were demonstrated near the anastomosis. Flow visualization studies demonstrated characteristic areas of boundary layer separation in the region of the adverse pressure gradients. The separation region involved both the main limb and the side arm. The separation forms a shell or ring of slow-moving fluid around the mainstream. Preliminary studies with pulsatile flow and with blood demonstrate that boundary layer separation occurs under clinical flow conditions. Boundary layer separation may play a role in the development of anastomotic hyperplasia and atherosclerotic deposits in the vicinity of surgical anastomoses."} {"id": "PMID:160774", "title": "A mechanism for the depression of contact sensitivity with B-cell mitogens.", "content": "LPS or DxS impair contact sensitivity to oxazolone in mice, evaluated as ear thickness and DNA synthesis of regional lymph node cells in vitro. Lymphoid cells from LPS- or DxS-injected and sensitized mice were able to transfer specifically the suppression when injected into animals sensitized immediately before cell transfer. This cell suppressor activity was eliminated by nylon wool filtration. These results suggest that B-cell mitogens may enhance suppressor cell activity of regulatory cells which arise during conventional immunization.", "contents": "A mechanism for the depression of contact sensitivity with B-cell mitogens. LPS or DxS impair contact sensitivity to oxazolone in mice, evaluated as ear thickness and DNA synthesis of regional lymph node cells in vitro. Lymphoid cells from LPS- or DxS-injected and sensitized mice were able to transfer specifically the suppression when injected into animals sensitized immediately before cell transfer. This cell suppressor activity was eliminated by nylon wool filtration. These results suggest that B-cell mitogens may enhance suppressor cell activity of regulatory cells which arise during conventional immunization."} {"id": "PMID:160778", "title": "Graft infection or graft reaction?", "content": "A perigraft reaction has been described that has been found to be free of infection, with a microscopic picture compatible to an immunologic-like reaction. Varied time intervals between onset of reaction and removal of tissue have allowed for a histopathologic staging. Note is made that four of the five grafts involved were external velour Dacron, with a question remaining as to whether the double velour stimulates an intensified hyperimmune response. Graft replacement by way of new uninvolved plains of tissue has not been necessary. Replacement with polytetrafluoroethylene through the same pathway resulted in prompt healing of wounds with no evidence of recurrent reaction.", "contents": "Graft infection or graft reaction? A perigraft reaction has been described that has been found to be free of infection, with a microscopic picture compatible to an immunologic-like reaction. Varied time intervals between onset of reaction and removal of tissue have allowed for a histopathologic staging. Note is made that four of the five grafts involved were external velour Dacron, with a question remaining as to whether the double velour stimulates an intensified hyperimmune response. Graft replacement by way of new uninvolved plains of tissue has not been necessary. Replacement with polytetrafluoroethylene through the same pathway resulted in prompt healing of wounds with no evidence of recurrent reaction."} {"id": "PMID:160784", "title": "The Princess Margaret Hospital Dental Unit.", "content": "This article describes the development of the Dental Department at Princess Margaret Hospital, Perth, Western Australia from its beginnings with the appointment of the first Honorary dentist in 1910. It details its state today as a comprehensive unit in which all dental specialities are represented and capable of handling any clinical or teaching duties which may present. Princess Margaret Hospital is a large general teaching children's hospital of three hundred beds which handles one third of child admissions in the State. In addition, virtually all congenital abnormalities and conditions requiring specialized unit treatment are admitted. Into this hospital the Dental Department has become fully integrated over the past thirteen years.", "contents": "The Princess Margaret Hospital Dental Unit. This article describes the development of the Dental Department at Princess Margaret Hospital, Perth, Western Australia from its beginnings with the appointment of the first Honorary dentist in 1910. It details its state today as a comprehensive unit in which all dental specialities are represented and capable of handling any clinical or teaching duties which may present. Princess Margaret Hospital is a large general teaching children's hospital of three hundred beds which handles one third of child admissions in the State. In addition, virtually all congenital abnormalities and conditions requiring specialized unit treatment are admitted. Into this hospital the Dental Department has become fully integrated over the past thirteen years."} {"id": "PMID:160785", "title": "Some reflections on the work of the Committee for the Dental Care of Handicapped Children (N.S.W. Branch).", "content": "The history of the committee for the Dental Care of Handicapped Children (N.S.W. Branch) is presented. There is some discussion on the difficulties of establishing just how many children there are, the concern of members of the profession and many people involved with their every-day care for their dental health, the results and some conclusions arrived at from questionnaires forwarded to voluntary organizations and dentists, the need for the involvement of dental educators, the difficulties encountered in the actual implementation of the concept, the task of the Dental Services Division and the Government Anaesthetic Service of the Health Commission of New South Wales in allocating manpower resources, and, finally, some inferences to be drawn as a result of being involved in the scheme.", "contents": "Some reflections on the work of the Committee for the Dental Care of Handicapped Children (N.S.W. Branch). The history of the committee for the Dental Care of Handicapped Children (N.S.W. Branch) is presented. There is some discussion on the difficulties of establishing just how many children there are, the concern of members of the profession and many people involved with their every-day care for their dental health, the results and some conclusions arrived at from questionnaires forwarded to voluntary organizations and dentists, the need for the involvement of dental educators, the difficulties encountered in the actual implementation of the concept, the task of the Dental Services Division and the Government Anaesthetic Service of the Health Commission of New South Wales in allocating manpower resources, and, finally, some inferences to be drawn as a result of being involved in the scheme."} {"id": "PMID:160786", "title": "Dental management of the chronically ill child.", "content": "Recent advances in the medical management of chronically ill children are of interest to the general dental practitioner in those areas which relate to groups of child patients frequently treated in practice. There is now a greater understanding of the effects on the child with a chronic illness or handicap of multiple visits to hospital or medical consultants, and of hospitalization for extended periods with separation from parents and family. The bearing this has on our dental management of such children is considered, as also are the recent advances in the care of children with congenital cardiac defects, haematological disorders, and neurological disturbances.", "contents": "Dental management of the chronically ill child. Recent advances in the medical management of chronically ill children are of interest to the general dental practitioner in those areas which relate to groups of child patients frequently treated in practice. There is now a greater understanding of the effects on the child with a chronic illness or handicap of multiple visits to hospital or medical consultants, and of hospitalization for extended periods with separation from parents and family. The bearing this has on our dental management of such children is considered, as also are the recent advances in the care of children with congenital cardiac defects, haematological disorders, and neurological disturbances."} {"id": "PMID:160788", "title": "Dermatophytoses: a clinical and management review.", "content": "The diagnosis and management of dermatophytic fungal infections depends upon a knowledge of the causative organism fungi, the morphological patterns which can be produced and the type, extent and duration of treatment necessary to effect cure.", "contents": "Dermatophytoses: a clinical and management review. The diagnosis and management of dermatophytic fungal infections depends upon a knowledge of the causative organism fungi, the morphological patterns which can be produced and the type, extent and duration of treatment necessary to effect cure."} {"id": "PMID:160791", "title": "The kinetics of effector binding to phosphofructokinase. The allosteric conformational transition induced by 1,N6-ethenoadenosine triphosphate.", "content": "1. The fluorescent ATP analogue 1,N6-etheno-ATP is a good substrate and an efficient allosteric inhibitor of rabbit skeletal-muscle phosphofructokinase. 2. Fluorescence energy transfer occurs between bound 1,N6-etheno-ATP and phosphofructokinase. 1,N6-Etheno-ATP fluorescence is enhanced, intrinsic protein fluorescence is quenched, and the excitation spectrum of 1,N6-etheno-ATP fluorescence is characteristic of protein absorption. 3. The binding reaction of 1,N6-etheno-ATP observed by stopped-flow fluorimetry is biphasic. The fast phase results from binding to the catalytic site alone. The slow phase results from the allosteric transition of the R conformation into the T conformation induced by the binding of 1,N6-etheno-ATP to the regulatory site. 4. The fluorescence signal that allows the transition of the R conformation into the T conformation to be observed does not arise from 1,N6-etheno-ATP bound to the regulatory site. It arises instead from 1,N6-etheno-ATP bound to the catalytic site as a consequence of changes at the catalytic site caused by the transition of the R conformation into the T conformation. 5. In the presence of excess of Mg2+, the affinity of 1,N6-etheno-ATP for the regulatory site is very much greater in the T state than in the R state.", "contents": "The kinetics of effector binding to phosphofructokinase. The allosteric conformational transition induced by 1,N6-ethenoadenosine triphosphate. 1. The fluorescent ATP analogue 1,N6-etheno-ATP is a good substrate and an efficient allosteric inhibitor of rabbit skeletal-muscle phosphofructokinase. 2. Fluorescence energy transfer occurs between bound 1,N6-etheno-ATP and phosphofructokinase. 1,N6-Etheno-ATP fluorescence is enhanced, intrinsic protein fluorescence is quenched, and the excitation spectrum of 1,N6-etheno-ATP fluorescence is characteristic of protein absorption. 3. The binding reaction of 1,N6-etheno-ATP observed by stopped-flow fluorimetry is biphasic. The fast phase results from binding to the catalytic site alone. The slow phase results from the allosteric transition of the R conformation into the T conformation induced by the binding of 1,N6-etheno-ATP to the regulatory site. 4. The fluorescence signal that allows the transition of the R conformation into the T conformation to be observed does not arise from 1,N6-etheno-ATP bound to the regulatory site. It arises instead from 1,N6-etheno-ATP bound to the catalytic site as a consequence of changes at the catalytic site caused by the transition of the R conformation into the T conformation. 5. In the presence of excess of Mg2+, the affinity of 1,N6-etheno-ATP for the regulatory site is very much greater in the T state than in the R state."} {"id": "PMID:160792", "title": "The rate-limiting step of the protamine-induced adenosine triphosphatase activity of adenosine triphosphate-G-actin.", "content": "The release of Pi from the Pi-G-actin-ADP complex is the rate-limiting step in the ATPase activity that is shown by ATP-G-actin in the presence of protamine.", "contents": "The rate-limiting step of the protamine-induced adenosine triphosphatase activity of adenosine triphosphate-G-actin. The release of Pi from the Pi-G-actin-ADP complex is the rate-limiting step in the ATPase activity that is shown by ATP-G-actin in the presence of protamine."} {"id": "PMID:160793", "title": "Effects of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on rabbit articular chondrocytes in culture.", "content": "Investigations were carried out to assess the effects of disodium 1-hydroxyethane-1,1-diphosphonate and disodium dichloromethanediphosphonate (compounds containing a P-C-P bond) on isolated rabbit articular chondrocytes in culture. Studies on growth behaviour showed that both diphosphonates displayed inhibitory actions, dichloromethanediphosphonate producing the larger effect. Both compounds inhibited the uptake of 2-deoxy-d-glucose, dichloromethanediphosphonate once more being the more potent of the two. The uptake of alpha-aminoisobutyrate was considerably increased by chondrocytes treated with dichloromethanediphosphonate, whereas 1-hydroxyethane-1,1-diphosphonate showed no effects. The biosynthesis of sulphated extracellular macromolecules secreted by the cells into the pericellular space as well as into the growth medium was greatly increased by dichloromethanediphosphonate but not by 1-hydroxyethane-1,1-diphosphonate. The stimulatory effect was dose-dependent. Short-term exposure of already confluent cells to dichloromethanediphosphonate as opposed to growing the cells to confluence in the presence of the diphosphonate revealed that the stimulatory effects were already evident after 24h, indicating that cell division is not necessarily required to produce the observed effects. The increment in proteoglycan synthesis was still evident with cells that were exposed continuously to the diphosphonate in primary as well as secondary culture. Pulse-chase experiments together with studies on the enzyme arylsulphatase revealed that the appearance of increased amounts of proteoglycans was the result of a stimulation in synthesis and not due to an inhibition in turnover.", "contents": "Effects of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on rabbit articular chondrocytes in culture. Investigations were carried out to assess the effects of disodium 1-hydroxyethane-1,1-diphosphonate and disodium dichloromethanediphosphonate (compounds containing a P-C-P bond) on isolated rabbit articular chondrocytes in culture. Studies on growth behaviour showed that both diphosphonates displayed inhibitory actions, dichloromethanediphosphonate producing the larger effect. Both compounds inhibited the uptake of 2-deoxy-d-glucose, dichloromethanediphosphonate once more being the more potent of the two. The uptake of alpha-aminoisobutyrate was considerably increased by chondrocytes treated with dichloromethanediphosphonate, whereas 1-hydroxyethane-1,1-diphosphonate showed no effects. The biosynthesis of sulphated extracellular macromolecules secreted by the cells into the pericellular space as well as into the growth medium was greatly increased by dichloromethanediphosphonate but not by 1-hydroxyethane-1,1-diphosphonate. The stimulatory effect was dose-dependent. Short-term exposure of already confluent cells to dichloromethanediphosphonate as opposed to growing the cells to confluence in the presence of the diphosphonate revealed that the stimulatory effects were already evident after 24h, indicating that cell division is not necessarily required to produce the observed effects. The increment in proteoglycan synthesis was still evident with cells that were exposed continuously to the diphosphonate in primary as well as secondary culture. Pulse-chase experiments together with studies on the enzyme arylsulphatase revealed that the appearance of increased amounts of proteoglycans was the result of a stimulation in synthesis and not due to an inhibition in turnover."} {"id": "PMID:160789", "title": "Efficacy of Linco-Spectin medication on mycoplasma meleagridis airsacculitis in turkey poults.", "content": "The efficacy of Linco-Spectin (LS) water medication was determined against Mycoplasma meleagridis (MM) airsacculitis in turkey poults under controlled conditions. The poults were obtained from commercial flocks naturally infected with MM. Water medication was given for the first five days of life. In Georgia and Ohio, LS was given at 0, 1, 2, and 4 g per gallon of drinking water. In California and Minnesota, LS was administered at 0 and 2 g per gallon of drinking water. At three weeks old, the birds were weighed individually and examined serologically, culturally, and grossly for MM airsacculitis. LS at 2 g activity per gallon of drinking water was beneficial in controlling MM airsacculitis in all four trials.", "contents": "Efficacy of Linco-Spectin medication on mycoplasma meleagridis airsacculitis in turkey poults. The efficacy of Linco-Spectin (LS) water medication was determined against Mycoplasma meleagridis (MM) airsacculitis in turkey poults under controlled conditions. The poults were obtained from commercial flocks naturally infected with MM. Water medication was given for the first five days of life. In Georgia and Ohio, LS was given at 0, 1, 2, and 4 g per gallon of drinking water. In California and Minnesota, LS was administered at 0 and 2 g per gallon of drinking water. At three weeks old, the birds were weighed individually and examined serologically, culturally, and grossly for MM airsacculitis. LS at 2 g activity per gallon of drinking water was beneficial in controlling MM airsacculitis in all four trials."} {"id": "PMID:160801", "title": "Idiopathic neutropenia with normocellular bone marrow: an immune-complex disease.", "content": "The presence of circulating immune-complexes (IC) and their in vivo interaction with polymorphonuclear neutrophils (PMN) have been detected in two cases of idiopathic neutropenia with normocellular bone marrow. The injection of patients' sera into New Zealand White rabbits caused a striking neutropenia due to sequestration of PMN in the vascular bed of kidneys and lungs. The kinetics of PMN disappearance from peripheral blood and the pattern of sequestration overlapped that induced by the injection of pre-formed soluble IC. Treatment with plasmapheresis caused an early and lasting increase of PMN; rabbit PMN were almost unaffected by the injection of patient serum after the course of plasmapheresis. These data are consistent with the possibility that idiopathic neutropenia with normocellular bone marrow may be caused by persistent in vivo interaction between IC and circulating PMN.", "contents": "Idiopathic neutropenia with normocellular bone marrow: an immune-complex disease. The presence of circulating immune-complexes (IC) and their in vivo interaction with polymorphonuclear neutrophils (PMN) have been detected in two cases of idiopathic neutropenia with normocellular bone marrow. The injection of patients' sera into New Zealand White rabbits caused a striking neutropenia due to sequestration of PMN in the vascular bed of kidneys and lungs. The kinetics of PMN disappearance from peripheral blood and the pattern of sequestration overlapped that induced by the injection of pre-formed soluble IC. Treatment with plasmapheresis caused an early and lasting increase of PMN; rabbit PMN were almost unaffected by the injection of patient serum after the course of plasmapheresis. These data are consistent with the possibility that idiopathic neutropenia with normocellular bone marrow may be caused by persistent in vivo interaction between IC and circulating PMN."} {"id": "PMID:160802", "title": "The use of EMG feedback and progressive relaxation in the treatment of a woman with chronic back pain.", "content": "In this systematic single-case study, a 71-year-old white female with chronic back pain and paravertebral muscle spasm was treated with 17 sessions of electromyographic (EMG) feedback, with recording site just below the right inferior scapular angle. Progressive relaxation practice was also employed. EMG level was monitored during baseline, treatment, and follow-up phases. Backaches were recorded by the subject on a daily basis. There was a marked decrease in both EMG level and frequency of backaches, as well as an increase in activities at home. Improvement was maintained 12 weeks after the last treatment session.", "contents": "The use of EMG feedback and progressive relaxation in the treatment of a woman with chronic back pain. In this systematic single-case study, a 71-year-old white female with chronic back pain and paravertebral muscle spasm was treated with 17 sessions of electromyographic (EMG) feedback, with recording site just below the right inferior scapular angle. Progressive relaxation practice was also employed. EMG level was monitored during baseline, treatment, and follow-up phases. Backaches were recorded by the subject on a daily basis. There was a marked decrease in both EMG level and frequency of backaches, as well as an increase in activities at home. Improvement was maintained 12 weeks after the last treatment session."} {"id": "PMID:160803", "title": "Granulocytic chalone is not a polyamine complex.", "content": "Recent studies have indicated that tissue extracts may contain sufficient amounts of free polyamines to account for the inhibitory effect of the extracts and hence mask any authentic chalone action. It has also been reported that bound polyamine may be the active moiety of some chalones. We show here that in our granulocytic and lymphocytic chalones polyamines, either free or bound, are not responsible for the inhibitory effects of the preparation.", "contents": "Granulocytic chalone is not a polyamine complex. Recent studies have indicated that tissue extracts may contain sufficient amounts of free polyamines to account for the inhibitory effect of the extracts and hence mask any authentic chalone action. It has also been reported that bound polyamine may be the active moiety of some chalones. We show here that in our granulocytic and lymphocytic chalones polyamines, either free or bound, are not responsible for the inhibitory effects of the preparation."} {"id": "PMID:160811", "title": "[Use of the concanavalin-peroxidase-DAB system for identification of human chromosomes].", "content": "The effect of concanavalin A on the prometaphase chromosomes was investigated, using a staining reaction based on the peroxydase-diaminobenzidin-H2O2 system. After incubation with concanavalina A, the chromosomes telomeres as well as the centromeres and satellites of the acrocentric chromosomes were strongly stained. Sometimes the chromatids appeared to be coiled. In other respect, it must be noted that peroxydase alone can stain the chromatids, which probably means that this compounds is able to unite with the chromosomes, without the aid of concanavalin A.", "contents": "[Use of the concanavalin-peroxidase-DAB system for identification of human chromosomes]. The effect of concanavalin A on the prometaphase chromosomes was investigated, using a staining reaction based on the peroxydase-diaminobenzidin-H2O2 system. After incubation with concanavalina A, the chromosomes telomeres as well as the centromeres and satellites of the acrocentric chromosomes were strongly stained. Sometimes the chromatids appeared to be coiled. In other respect, it must be noted that peroxydase alone can stain the chromatids, which probably means that this compounds is able to unite with the chromosomes, without the aid of concanavalin A."} {"id": "PMID:160812", "title": "[Excito-motor action of succinyldicholine and inhibitory action of acetylcholine on slow muscle, the frog hypoglossus].", "content": "We have registered contraction of the frog's hyoglossus which is essentially slow. By injecting succinyldicholin in the heart ventricle, we have elicited contractions which prove definitively the motor effect of this cholin ester on the slow muscular fibers. Acetylcholin, injected in the lymph vessels to avoid its effect on the heart, does not contract the hyoglossus. On the contrary, by exciting electrically the hypoglossus nerve, which commands the hyoglossus, we have observed that this mono-ester abolishes the neuro-muscular transmission, as in the curare intoxication. We have found the same phenomenon on the rat's semi-tendinosus which is a slow muscle too. The twitches produced by the ischiaticus are diminished significantly after the injection of acetylcholin in the jugular vein.", "contents": "[Excito-motor action of succinyldicholine and inhibitory action of acetylcholine on slow muscle, the frog hypoglossus]. We have registered contraction of the frog's hyoglossus which is essentially slow. By injecting succinyldicholin in the heart ventricle, we have elicited contractions which prove definitively the motor effect of this cholin ester on the slow muscular fibers. Acetylcholin, injected in the lymph vessels to avoid its effect on the heart, does not contract the hyoglossus. On the contrary, by exciting electrically the hypoglossus nerve, which commands the hyoglossus, we have observed that this mono-ester abolishes the neuro-muscular transmission, as in the curare intoxication. We have found the same phenomenon on the rat's semi-tendinosus which is a slow muscle too. The twitches produced by the ischiaticus are diminished significantly after the injection of acetylcholin in the jugular vein."} {"id": "PMID:160813", "title": "[Spinal cord potentials evoked by stimulation of cutaneous afferents in the cat spine (evidence of an N3 wave)].", "content": "Negative intermediary cord potentials evoked by low threshold cutaneous afferents were recorded from the surface of the lumbosacral spinal cord. In addition to the N1, N2 waves classically described, it is possible to distinguish a third one names here N3 wave. The characteristics and longitudinal distribution of this wave are different from those of N1 or N2.", "contents": "[Spinal cord potentials evoked by stimulation of cutaneous afferents in the cat spine (evidence of an N3 wave)]. Negative intermediary cord potentials evoked by low threshold cutaneous afferents were recorded from the surface of the lumbosacral spinal cord. In addition to the N1, N2 waves classically described, it is possible to distinguish a third one names here N3 wave. The characteristics and longitudinal distribution of this wave are different from those of N1 or N2."} {"id": "PMID:160809", "title": "Hill tribe opium addicts: a retrospective study of 1,382 patients.", "content": "This paper presents the results of a retrospective study of 1,382 patients admitted to the Narcotics Treatment Centre for Hill Tribes in Thailand, which was operated by the WHO/UN/Thai Programme for Drug Abuse Control. The study revealed widespread opium addiction among the hill tribes. Of these, the Karen were the largest group. Mean age on admission for treatment was 35 years. The male:female ratio was 7:1. Sixty-six per cent were heads of households. About one-third came from households with more than one addict. The mean duration of daily opium use before admission was 7.9 years. Over 90% of them were addicted to opium; there were eight heroin users. The mean amount of opium used daily was 3.9 g for males and 3.2 g for females. About three-quarters of them used salicylate analgesics with opium. Illness, in particular abdominal pain, was the most frequent cause of their addiction.", "contents": "Hill tribe opium addicts: a retrospective study of 1,382 patients. This paper presents the results of a retrospective study of 1,382 patients admitted to the Narcotics Treatment Centre for Hill Tribes in Thailand, which was operated by the WHO/UN/Thai Programme for Drug Abuse Control. The study revealed widespread opium addiction among the hill tribes. Of these, the Karen were the largest group. Mean age on admission for treatment was 35 years. The male:female ratio was 7:1. Sixty-six per cent were heads of households. About one-third came from households with more than one addict. The mean duration of daily opium use before admission was 7.9 years. Over 90% of them were addicted to opium; there were eight heroin users. The mean amount of opium used daily was 3.9 g for males and 3.2 g for females. About three-quarters of them used salicylate analgesics with opium. Illness, in particular abdominal pain, was the most frequent cause of their addiction."} {"id": "PMID:160814", "title": "[Measurement of homovanillic acid in urine of newborns and in older children].", "content": "In this study, the urinary H.V.A. of new borns and of older children was measured. The urinary H.V.A. titer of the new borns was found to be significantly greater than in older children. Moreover the increase is more pronounced when those infants are born prematurely. Former studies have shown that the metabolism of central nervous system catecholamine reflected by the urinary titers of H.V.A. is as accurate as titers measured in the CSF. Recently several authors have found increased titers of urinary H.V.A. in autistic children. It is therefore possible that the elevated urinary H.V.A. titers in the new born are due to an immaturity of the dopaminergic structures. Blocking these structures provokes an accelerated catecholamine turnover, thereby increasing the levels of catecholamines metabolites (most notably H.V.A.).", "contents": "[Measurement of homovanillic acid in urine of newborns and in older children]. In this study, the urinary H.V.A. of new borns and of older children was measured. The urinary H.V.A. titer of the new borns was found to be significantly greater than in older children. Moreover the increase is more pronounced when those infants are born prematurely. Former studies have shown that the metabolism of central nervous system catecholamine reflected by the urinary titers of H.V.A. is as accurate as titers measured in the CSF. Recently several authors have found increased titers of urinary H.V.A. in autistic children. It is therefore possible that the elevated urinary H.V.A. titers in the new born are due to an immaturity of the dopaminergic structures. Blocking these structures provokes an accelerated catecholamine turnover, thereby increasing the levels of catecholamines metabolites (most notably H.V.A.)."} {"id": "PMID:160815", "title": "[Histologic aspects of some organs in the alloxan induced diabetic mouse].", "content": "In order to study the modifications in the activity on some CNS drugs by the experimental diabetes, the authors are proposing a model of alloxanic diabetes in the mouse. Diabetes is induced by administering pure alloxan to a well selected brand of mice. Biochemical and histological observations obtained on different vital organs are comparable with those obtained with spontaneously diabetic mice (stable and steady glycemia). This model is consequently a good way of assessing pharmacological comparison.", "contents": "[Histologic aspects of some organs in the alloxan induced diabetic mouse]. In order to study the modifications in the activity on some CNS drugs by the experimental diabetes, the authors are proposing a model of alloxanic diabetes in the mouse. Diabetes is induced by administering pure alloxan to a well selected brand of mice. Biochemical and histological observations obtained on different vital organs are comparable with those obtained with spontaneously diabetic mice (stable and steady glycemia). This model is consequently a good way of assessing pharmacological comparison."} {"id": "PMID:160816", "title": "[Modification of the deep pineal after ablation of the superficial epiphysis in the golden hamster].", "content": "In various species (among Rodents: Mesocricetus auratus, Cricetus cricetus, Mus musculus, Meriones libycus, M. shawi et M. crassus; among Cheiroptera: Artibeus jamaicensis etc), the pineal complex is formed by two different portions one superficial situated under the cerebral dura and one deep portion situated between the habenular and posterior commissures. Superficial and deep portions are separated by a tractus of fibers and some pineal cells. Superficial epiphysectomy in the Mesocricetus auratus determines an increase in volume of the deep pineal. The nuclear diameter is also enlarged in this case. The functions of both superficial and deep pineal seem to be closely related. Superficial epiphysectomy is not followed by involution or hypoactivity of the deep pineal. Superficial epiphysectomy also determines changes in the subcommissural and subfornical organs.", "contents": "[Modification of the deep pineal after ablation of the superficial epiphysis in the golden hamster]. In various species (among Rodents: Mesocricetus auratus, Cricetus cricetus, Mus musculus, Meriones libycus, M. shawi et M. crassus; among Cheiroptera: Artibeus jamaicensis etc), the pineal complex is formed by two different portions one superficial situated under the cerebral dura and one deep portion situated between the habenular and posterior commissures. Superficial and deep portions are separated by a tractus of fibers and some pineal cells. Superficial epiphysectomy in the Mesocricetus auratus determines an increase in volume of the deep pineal. The nuclear diameter is also enlarged in this case. The functions of both superficial and deep pineal seem to be closely related. Superficial epiphysectomy is not followed by involution or hypoactivity of the deep pineal. Superficial epiphysectomy also determines changes in the subcommissural and subfornical organs."} {"id": "PMID:160817", "title": "[Role of dental pulp in the histogenesis of the enamel organ].", "content": "The histological study of in vitro cultured associations between dental pulps and outer dental epithelium showed that the predontoblasts initiated the histogenesis of the enamel organ and particularly the differentiation of the inner dental epithelium.", "contents": "[Role of dental pulp in the histogenesis of the enamel organ]. The histological study of in vitro cultured associations between dental pulps and outer dental epithelium showed that the predontoblasts initiated the histogenesis of the enamel organ and particularly the differentiation of the inner dental epithelium."} {"id": "PMID:160818", "title": "[Partial left ovariectomy in the hen: response of the gonadic residue].", "content": "The removal of the left ovary determines a modification of the hormonal environment in the hen, as indicated by the structure of the regenerat frequency observed. Indeed, comparated to the left ovary of the normal females, they present more big follicle and more active steroid cells of the internal theca. This gives evidence of a high stimulation.", "contents": "[Partial left ovariectomy in the hen: response of the gonadic residue]. The removal of the left ovary determines a modification of the hormonal environment in the hen, as indicated by the structure of the regenerat frequency observed. Indeed, comparated to the left ovary of the normal females, they present more big follicle and more active steroid cells of the internal theca. This gives evidence of a high stimulation."} {"id": "PMID:160819", "title": "[Cutaneous and subcutaneous blood flow measurement in rabbit's ear by epicutaneous diffusion of xenon 133. Influence of the arteriovenous anastomosis].", "content": "The cutaneous and subcutaneous blood flow measurement by a diffusible inert gas concerns theorically capillary nutritional flow. In clinical routine, where pathological openning of arteriovenous anastomosis is suspected, the blood flows measured by Xenon technic are often increased. The function of the shunts are displayed on the epuration curve obtained on a region where there are numerous: rabbit's ear.", "contents": "[Cutaneous and subcutaneous blood flow measurement in rabbit's ear by epicutaneous diffusion of xenon 133. Influence of the arteriovenous anastomosis]. The cutaneous and subcutaneous blood flow measurement by a diffusible inert gas concerns theorically capillary nutritional flow. In clinical routine, where pathological openning of arteriovenous anastomosis is suspected, the blood flows measured by Xenon technic are often increased. The function of the shunts are displayed on the epuration curve obtained on a region where there are numerous: rabbit's ear."} {"id": "PMID:160820", "title": "[Scintigraphic analysis, with the help of functional images].", "content": "Functional images are a new technique for analysis and visualization biological values. Each point of the organ is substitute by a functional value, representative of local uptake. This type of processing is interesting as the dynamic information gained is stored in a concentrated form, which can be easily reproduced and filed.", "contents": "[Scintigraphic analysis, with the help of functional images]. Functional images are a new technique for analysis and visualization biological values. Each point of the organ is substitute by a functional value, representative of local uptake. This type of processing is interesting as the dynamic information gained is stored in a concentrated form, which can be easily reproduced and filed."} {"id": "PMID:160821", "title": "[Activation, by various aldoses, of dichlorophenol-indophenol reduction by endogenous constituents of a preparation of glucose dehydrogenase from Pseudomonas fluorescens].", "content": "Dichlorophenol-indophenol is reduced neither by D-glucose nor by the endogenous components of a particulate purified glucose-dehydrogenase from Pseudomonas fluorescens, when these two classes of compounds acts individually. In contrast, the dye is quickly reduced by the endogenous components when the reaction occurs in the presence of glucose, without a direct participation of glucose in the reduction. In this effect D-glucose can be replaced by D-mannose, D-galactose or D-xylose, but not by D-fructose.", "contents": "[Activation, by various aldoses, of dichlorophenol-indophenol reduction by endogenous constituents of a preparation of glucose dehydrogenase from Pseudomonas fluorescens]. Dichlorophenol-indophenol is reduced neither by D-glucose nor by the endogenous components of a particulate purified glucose-dehydrogenase from Pseudomonas fluorescens, when these two classes of compounds acts individually. In contrast, the dye is quickly reduced by the endogenous components when the reaction occurs in the presence of glucose, without a direct participation of glucose in the reduction. In this effect D-glucose can be replaced by D-mannose, D-galactose or D-xylose, but not by D-fructose."} {"id": "PMID:160822", "title": "[Effect of carbaryl on cultured embryonic chicken gonads in vitro].", "content": "Ovaries and testes from 9 day-old chick embryos have been explanted on media containing various levels of carbaryl. The pesticide action depends on the use doses. Histocytopathological effects were essentially observed upon gonocytes which degenerated.", "contents": "[Effect of carbaryl on cultured embryonic chicken gonads in vitro]. Ovaries and testes from 9 day-old chick embryos have been explanted on media containing various levels of carbaryl. The pesticide action depends on the use doses. Histocytopathological effects were essentially observed upon gonocytes which degenerated."} {"id": "PMID:160823", "title": "[Prolongation of the effective refractory period on isolated guinea pig atria by some anti-arrhythmia agents: relevance in a comparison of their potentialities].", "content": "The effects of bepridil, nifedipine, verapamil, lignoca\u00efne and amiodarone on the atrial effective refractory period were investigated in the guinea-pig. The observed results permitted elucidation of a remarkable activity by both nifedipine and verapamil, and by bepridil and lignoca\u00efne. In contrast, in the experimental conditions, no activity was detected with amiodarone up to concentrations of 10(-4) M. The efficacity rating of the test compounds is not reflected by their anti-arrhythmic efficacity as demonstrated in vivo in the animal, nor by their therapeutic anti-arrhythmic efficacity as reported in the clinical literature. However, this efficacity rating may be related to the interaction of the compounds with the transmembrane sodium or calcium movements.", "contents": "[Prolongation of the effective refractory period on isolated guinea pig atria by some anti-arrhythmia agents: relevance in a comparison of their potentialities]. The effects of bepridil, nifedipine, verapamil, lignoca\u00efne and amiodarone on the atrial effective refractory period were investigated in the guinea-pig. The observed results permitted elucidation of a remarkable activity by both nifedipine and verapamil, and by bepridil and lignoca\u00efne. In contrast, in the experimental conditions, no activity was detected with amiodarone up to concentrations of 10(-4) M. The efficacity rating of the test compounds is not reflected by their anti-arrhythmic efficacity as demonstrated in vivo in the animal, nor by their therapeutic anti-arrhythmic efficacity as reported in the clinical literature. However, this efficacity rating may be related to the interaction of the compounds with the transmembrane sodium or calcium movements."} {"id": "PMID:160824", "title": "[Determination of the adrenergic response by measurement of catecholamines and activity of dopamine-beta-hydroxylase (D-beta-B) in arterial capillary blood].", "content": "Plasma dopamine-beta-hydroxylase activity and catecholamines (adrenaline and noradrenaline) level in venous blood taken from the cubital vein and in arterialized capillary blood taken from the ear lobe were measured before and after a maximal exercise on a treadmill in 14 healthy untrained volunteers. The authors have shown a good correlation between these parameters in venous blood and those in capillary blood. It is concluded that the determination of plasma dopamine-beta-hydroxylase activity and catecholamines level in arterialized capillary blood could be a valid measure of the sympathetic activity.", "contents": "[Determination of the adrenergic response by measurement of catecholamines and activity of dopamine-beta-hydroxylase (D-beta-B) in arterial capillary blood]. Plasma dopamine-beta-hydroxylase activity and catecholamines (adrenaline and noradrenaline) level in venous blood taken from the cubital vein and in arterialized capillary blood taken from the ear lobe were measured before and after a maximal exercise on a treadmill in 14 healthy untrained volunteers. The authors have shown a good correlation between these parameters in venous blood and those in capillary blood. It is concluded that the determination of plasma dopamine-beta-hydroxylase activity and catecholamines level in arterialized capillary blood could be a valid measure of the sympathetic activity."} {"id": "PMID:160825", "title": "[Occurrence of giant nucleolar fibrillar centers in neurons of rat superior cervical ganglia during dark period: sterological analysis].", "content": "In the rat, fibrillar centers (nucleolar organizers) of neurons in superior cervical ganglia are small during light period whereas quite giant ones are observed during dark period. Stereological analysis demonstrates that mean volume of fibrillar centers which is 11.9 x 10(-2) micron 3 in light period increases up to 159 x 10(-2) micron 3 in dark period. So, the more or less development of fibrillar centers in these interphasic nuclei is a circadian phenomenon.", "contents": "[Occurrence of giant nucleolar fibrillar centers in neurons of rat superior cervical ganglia during dark period: sterological analysis]. In the rat, fibrillar centers (nucleolar organizers) of neurons in superior cervical ganglia are small during light period whereas quite giant ones are observed during dark period. Stereological analysis demonstrates that mean volume of fibrillar centers which is 11.9 x 10(-2) micron 3 in light period increases up to 159 x 10(-2) micron 3 in dark period. So, the more or less development of fibrillar centers in these interphasic nuclei is a circadian phenomenon."} {"id": "PMID:160826", "title": "[Tumor angiogenic activity (introductory note)].", "content": "Some classical experiments proving the existence of a Tumoral Angiogenic Factor are reproduced. They show the presence of T.A.F. in a solid tumor (Walker 256) and its apparent absence in a leukemia (L 1210). We point out that the biological activity oversteps the barrier of zoological class.", "contents": "[Tumor angiogenic activity (introductory note)]. Some classical experiments proving the existence of a Tumoral Angiogenic Factor are reproduced. They show the presence of T.A.F. in a solid tumor (Walker 256) and its apparent absence in a leukemia (L 1210). We point out that the biological activity oversteps the barrier of zoological class."} {"id": "PMID:160827", "title": "[Effect of the MgATP2- complex on liver phosphoglycerate kinase activity in the rat].", "content": "Effect of Mg ATP2- has been studied on purified rat liver phosphoglycerate kinase in the direction of glycolysis. Lineweaver-Burk analysis indicated that Mg ATP2- inhibition was noncompetitive with Mg ADP1- and 1, 3-diphosphoglycerate; the intersection point is above the 1/[S]-axis and two sites can be suspected for this inhibitor.", "contents": "[Effect of the MgATP2- complex on liver phosphoglycerate kinase activity in the rat]. Effect of Mg ATP2- has been studied on purified rat liver phosphoglycerate kinase in the direction of glycolysis. Lineweaver-Burk analysis indicated that Mg ATP2- inhibition was noncompetitive with Mg ADP1- and 1, 3-diphosphoglycerate; the intersection point is above the 1/[S]-axis and two sites can be suspected for this inhibitor."} {"id": "PMID:160828", "title": "[Evaluation of cell regeneration of bone marrow after fractional irradiation of the mouse in toto].", "content": "We have studied the recovery for mice bone marrow cells after fractionated irradiation of the whole body. The additional dose (Dr) to obtain a given biological effect if the irradiation is split in two equal subfractions (2 Di) separated by a short interval of time (i) is 40 rad per day when the interval of time between the two irradiations is lengthened of one day.", "contents": "[Evaluation of cell regeneration of bone marrow after fractional irradiation of the mouse in toto]. We have studied the recovery for mice bone marrow cells after fractionated irradiation of the whole body. The additional dose (Dr) to obtain a given biological effect if the irradiation is split in two equal subfractions (2 Di) separated by a short interval of time (i) is 40 rad per day when the interval of time between the two irradiations is lengthened of one day."} {"id": "PMID:160829", "title": "[Selective fixation of methylselenobenzoic acid by the pineal gland].", "content": "Investigation of the localization in the central nervous system of the rat of an epileptogenic agent, methylseleno-2-benzoic acid, did not lead to its selective distribution in the cerebral cortex or in the brainstem in relation with its biological activity. But a systematic study of the distribution of this compound labelled with 75Se at a high specific activity has revealed a rate of fixation by the pineal gland 4 to 5 times higher than that of other tissues of the central nervous system. After a survival time of 4 hours, the radioactivity of the pineal gland exceeds that of the blood. A parallel study of the distribution of the 75SeO3- ion on the one hand of the 35S homolog of the 75Se compound on the other hand has demonstrated that the fixation by the pineal gland is bound to the molecular structure of the selenium compound.", "contents": "[Selective fixation of methylselenobenzoic acid by the pineal gland]. Investigation of the localization in the central nervous system of the rat of an epileptogenic agent, methylseleno-2-benzoic acid, did not lead to its selective distribution in the cerebral cortex or in the brainstem in relation with its biological activity. But a systematic study of the distribution of this compound labelled with 75Se at a high specific activity has revealed a rate of fixation by the pineal gland 4 to 5 times higher than that of other tissues of the central nervous system. After a survival time of 4 hours, the radioactivity of the pineal gland exceeds that of the blood. A parallel study of the distribution of the 75SeO3- ion on the one hand of the 35S homolog of the 75Se compound on the other hand has demonstrated that the fixation by the pineal gland is bound to the molecular structure of the selenium compound."} {"id": "PMID:160830", "title": "[Role of platelets in arterial hypotension induced by arachidonic acid and in carrageenan induced edema in the rat].", "content": "When rat platelets are incubated in vitro in the presence of aspirin, the formation of malonaldehyde from arachidonic acid is inhibited. The production of malonaldehyde reflects the synthesis of prostaglandins and associated compounds. The same inhibition is found when the platelets originate from rats pretreated with aspirin. Small doses of aspirin are active in vitro and 10-20 mg/kg in vivo. This dosage of aspirin does not affect the hypotensive activity of arachidonic acid nor the oedematous properties of carrageenan in the rat. These two effects are thus independent from the prostaglandins formed in the platelets.", "contents": "[Role of platelets in arterial hypotension induced by arachidonic acid and in carrageenan induced edema in the rat]. When rat platelets are incubated in vitro in the presence of aspirin, the formation of malonaldehyde from arachidonic acid is inhibited. The production of malonaldehyde reflects the synthesis of prostaglandins and associated compounds. The same inhibition is found when the platelets originate from rats pretreated with aspirin. Small doses of aspirin are active in vitro and 10-20 mg/kg in vivo. This dosage of aspirin does not affect the hypotensive activity of arachidonic acid nor the oedematous properties of carrageenan in the rat. These two effects are thus independent from the prostaglandins formed in the platelets."} {"id": "PMID:160831", "title": "[Effect of oxamethacin and sulindac on prostaglandin synthesis].", "content": "1. Indomethacin and oxamethacin reduce the formation of malonaldehyde from arachidonic acid by rat platelets in vitro. Sulindac has no influence on this formation. 2. Indomethacin, oxamethacin and sulindac inhibit the action of arachidonic acid on the rat stomach strips in vitro. 3. These three anti-inflammatory drugs suppress the hypotensive activity of arachidonic acid in the rat in vivo. 4. The comparison of the inhibitory activities of these drugs in vivo and in vitro shows that sulindac is converted to a potent anti-prostaglandin-synthetase metabolite and that a part of the action of oxamethacin depends on its conversion to indomethacin in the rat.", "contents": "[Effect of oxamethacin and sulindac on prostaglandin synthesis]. 1. Indomethacin and oxamethacin reduce the formation of malonaldehyde from arachidonic acid by rat platelets in vitro. Sulindac has no influence on this formation. 2. Indomethacin, oxamethacin and sulindac inhibit the action of arachidonic acid on the rat stomach strips in vitro. 3. These three anti-inflammatory drugs suppress the hypotensive activity of arachidonic acid in the rat in vivo. 4. The comparison of the inhibitory activities of these drugs in vivo and in vitro shows that sulindac is converted to a potent anti-prostaglandin-synthetase metabolite and that a part of the action of oxamethacin depends on its conversion to indomethacin in the rat."} {"id": "PMID:160832", "title": "[Allergic reaction to topical drugs].", "content": "It is important to differentiate worsening of a cutaneous eruption following topical therapy from lack of response to the medication. A study to determine the origin of contact dermatitis secondary to topical therapy was conducted among 87 patients with this kind of contact dermatitis. Sixteen patch tests with chemical compounds known to be allergenic were done. The following eight chemical compounds were responsible for 86.5% of the positive reactions observed: neomycin, ethylenediamine, mercury, benzocaine, iodochlorhydroxyquin, peruvian balsam, nitrofurazone and cinchocaine. More than half of the reactions were to neomycin, ethylenediamine and mercury. It is easier to diagnose this condition if one knows the composition of the topical medications one prescribes and the allergenic potency of their ingredients.", "contents": "[Allergic reaction to topical drugs]. It is important to differentiate worsening of a cutaneous eruption following topical therapy from lack of response to the medication. A study to determine the origin of contact dermatitis secondary to topical therapy was conducted among 87 patients with this kind of contact dermatitis. Sixteen patch tests with chemical compounds known to be allergenic were done. The following eight chemical compounds were responsible for 86.5% of the positive reactions observed: neomycin, ethylenediamine, mercury, benzocaine, iodochlorhydroxyquin, peruvian balsam, nitrofurazone and cinchocaine. More than half of the reactions were to neomycin, ethylenediamine and mercury. It is easier to diagnose this condition if one knows the composition of the topical medications one prescribes and the allergenic potency of their ingredients."} {"id": "PMID:160835", "title": "Treatment of acute nonlymphocytic leukemia with neocarzinostatin.", "content": "Neocarzinostatin (NCS) is a polypeptide antibiotic which has been shown to have antileukemic activity in Japanese trials. Twenty-two patients, who were in relapse with acute nonlymphocytic leukemia refractory to other agents, were studied with two dose schedules of NCS. Schedule 1, 2000-8000 units/m2/day by continuous infusion for 5-10 days, was given to 12 patients and schedule 2, 2000-6000 units/m2/day by iv bolus every 8 hours, was given to ten patients. Clearing of peripheral blast cell was seen in nine of 12 patients treated with schedule 1 and in four of ten patients treated with schedule 2. Bone marrow effect was variable and appeared to be dose-related. No unequivocal complete remissions were seen with either schedule. NCS perturbations of cycling bone marrow cells were studied in two patients receiving the drug by continuous infusion. Both of these patients showed G2 accumulation of marrow cells following treatment. Immunochemically detectable levels of drug were seen in three patients treated with continuous infusion. In summary, NCS has antileukemic effect in patients with acute nonlymphocytic leukemia refractory to other agents. However, its role in the therapy for acute leukemia required further evaluation.", "contents": "Treatment of acute nonlymphocytic leukemia with neocarzinostatin. Neocarzinostatin (NCS) is a polypeptide antibiotic which has been shown to have antileukemic activity in Japanese trials. Twenty-two patients, who were in relapse with acute nonlymphocytic leukemia refractory to other agents, were studied with two dose schedules of NCS. Schedule 1, 2000-8000 units/m2/day by continuous infusion for 5-10 days, was given to 12 patients and schedule 2, 2000-6000 units/m2/day by iv bolus every 8 hours, was given to ten patients. Clearing of peripheral blast cell was seen in nine of 12 patients treated with schedule 1 and in four of ten patients treated with schedule 2. Bone marrow effect was variable and appeared to be dose-related. No unequivocal complete remissions were seen with either schedule. NCS perturbations of cycling bone marrow cells were studied in two patients receiving the drug by continuous infusion. Both of these patients showed G2 accumulation of marrow cells following treatment. Immunochemically detectable levels of drug were seen in three patients treated with continuous infusion. In summary, NCS has antileukemic effect in patients with acute nonlymphocytic leukemia refractory to other agents. However, its role in the therapy for acute leukemia required further evaluation."} {"id": "PMID:160836", "title": "Continuous streptozotocin infusion: a phase I study.", "content": "Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise.", "contents": "Continuous streptozotocin infusion: a phase I study. Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise."} {"id": "PMID:160837", "title": "\"Adriamycin flare\": a skin reaction resembling extravasation.", "content": "One hundred consecutive patients were prospectively observed for the development of a local skin reaction to Adriamycin. A frequency of 3% was noted. \"Adriamycin flare\" is possibly an allergic reaction and could be confused with Adriamycin extravasation.", "contents": "\"Adriamycin flare\": a skin reaction resembling extravasation. One hundred consecutive patients were prospectively observed for the development of a local skin reaction to Adriamycin. A frequency of 3% was noted. \"Adriamycin flare\" is possibly an allergic reaction and could be confused with Adriamycin extravasation."} {"id": "PMID:160846", "title": "Intranasal ipratropium: a new treatment for perennial rhinitis.", "content": "Eighty micrograms of the topically active parasympatholytic ipratropium were applied intranasally 4 times a day to 20 adult patients with perennial rhinitis and severe watery rhinorrhoea in a double-blind placebo controlled cross-over trial. There was a significant reduction in nasal hypersecretion during ipratropium treatment. Fourteen patients preferred the ipratropium period, 3 the placebo period and 3 had no preference. There were no adverse systemic or local effects. Ipratropium was effective also in patients resistant to glucocorticoids, sodium cromoglycate and antihistaminics. As the drug works immediately it can also be used before exposure to known provocating factors. It is concluded that continuous use of this new medication is of value in the management of severe rhinorrhoea in patients with perennial rhinitis, and that the occasional use is helpful in subjects with infrequent attacks of nasal hypersecretion.", "contents": "Intranasal ipratropium: a new treatment for perennial rhinitis. Eighty micrograms of the topically active parasympatholytic ipratropium were applied intranasally 4 times a day to 20 adult patients with perennial rhinitis and severe watery rhinorrhoea in a double-blind placebo controlled cross-over trial. There was a significant reduction in nasal hypersecretion during ipratropium treatment. Fourteen patients preferred the ipratropium period, 3 the placebo period and 3 had no preference. There were no adverse systemic or local effects. Ipratropium was effective also in patients resistant to glucocorticoids, sodium cromoglycate and antihistaminics. As the drug works immediately it can also be used before exposure to known provocating factors. It is concluded that continuous use of this new medication is of value in the management of severe rhinorrhoea in patients with perennial rhinitis, and that the occasional use is helpful in subjects with infrequent attacks of nasal hypersecretion."} {"id": "PMID:160847", "title": "Mucopolysaccharides in osteochondrodysplasias.", "content": "Mucopolysaccharide (MPS) metabolism in cultured skin fibroblasts was studied in one case of each of the following osteochondrodysplasias: chondrodysplasia punctata of the rhizomelic type, thanatophoric dysplasia, campomelic dysplasia, and osteogenesis imperfecta congenita. Accumulation of both sulfated and non-sulfated MPS, as well as secretion of total MPS, was normal in chondrodysplasia punctata of the rhizomelic type and in thanatophoric dysplasia. Accumulation of both sulfated and non-sulfated MPS was normal in campomelic dysplasia. Lastly, accumulation of sulfated MPS was normal in osteogenesis imperfecta congenita.", "contents": "Mucopolysaccharides in osteochondrodysplasias. Mucopolysaccharide (MPS) metabolism in cultured skin fibroblasts was studied in one case of each of the following osteochondrodysplasias: chondrodysplasia punctata of the rhizomelic type, thanatophoric dysplasia, campomelic dysplasia, and osteogenesis imperfecta congenita. Accumulation of both sulfated and non-sulfated MPS, as well as secretion of total MPS, was normal in chondrodysplasia punctata of the rhizomelic type and in thanatophoric dysplasia. Accumulation of both sulfated and non-sulfated MPS was normal in campomelic dysplasia. Lastly, accumulation of sulfated MPS was normal in osteogenesis imperfecta congenita."} {"id": "PMID:160848", "title": "Down syndrome due to 21;21 translocation in a male twin.", "content": "A spontaneous 21;21 translocation resulting in features consistent with Down syndrome is reported in the first born of male fraternal twins. No history of twinning or chromosomal abnormalities in the family was noted. Any association between dizygous twinning and Down syndrome due to de novo translocation remains speculative until a sufficient pool of published data is available from study of such families.", "contents": "Down syndrome due to 21;21 translocation in a male twin. A spontaneous 21;21 translocation resulting in features consistent with Down syndrome is reported in the first born of male fraternal twins. No history of twinning or chromosomal abnormalities in the family was noted. Any association between dizygous twinning and Down syndrome due to de novo translocation remains speculative until a sufficient pool of published data is available from study of such families."} {"id": "PMID:160844", "title": "[Epidemiologic study of dracunculosis in the Podokwos of the Mandara mountains (northern Cameroon)].", "content": "The purpose of the present work is the study of the epidemiological aspects of dracontiasis in an endemic area in Cameroon. The study was undertaken in the central Podokwo settlement in Mora subdivision. It is a mountainous area with a climate characterized by a long dry season, from October to mid-May, and a short rainy season. Two seasonal, streams run across the settlement. The water supply of the community is ensured throughout the year by two well built wells. During the rainy season, shallow unprotected wells are the water sources of about 80% of the inhabitants. Among the 944 subjects studied in our sample, 251 had the disease, corresponding to a prevalence of 26 6%. There is no significant difference between both sexes in the prevalence of the disease in our study. The age group 13-26 years is most affected. The worm load varies from 1 to 5, averagely 1.5. As to the localization of the worms in the body, in 92.7% of cases the worms is located in the lower limbs, the feet alone representing up to 46.8%. Less common sites of localization are the head, the breast, the external genitalia. The maximum rate of infestation is observed between August and September. Desinfection of wells with chemicals would be recommended during this period of time.", "contents": "[Epidemiologic study of dracunculosis in the Podokwos of the Mandara mountains (northern Cameroon)]. The purpose of the present work is the study of the epidemiological aspects of dracontiasis in an endemic area in Cameroon. The study was undertaken in the central Podokwo settlement in Mora subdivision. It is a mountainous area with a climate characterized by a long dry season, from October to mid-May, and a short rainy season. Two seasonal, streams run across the settlement. The water supply of the community is ensured throughout the year by two well built wells. During the rainy season, shallow unprotected wells are the water sources of about 80% of the inhabitants. Among the 944 subjects studied in our sample, 251 had the disease, corresponding to a prevalence of 26 6%. There is no significant difference between both sexes in the prevalence of the disease in our study. The age group 13-26 years is most affected. The worm load varies from 1 to 5, averagely 1.5. As to the localization of the worms in the body, in 92.7% of cases the worms is located in the lower limbs, the feet alone representing up to 46.8%. Less common sites of localization are the head, the breast, the external genitalia. The maximum rate of infestation is observed between August and September. Desinfection of wells with chemicals would be recommended during this period of time."} {"id": "PMID:160849", "title": "Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females.", "content": "An attempt was made to investigate the possible existence of differences in the composition of peripheral blood lymphocytes between males and females. Using affinity chromatography of human peripheral mononuclear cells on insolubilized histamine together with staining by fluoresceinated histamine-rabbit serum albumin (HRSA) we revealed that males possess a significantly higher proportion of mononuclear cells which bind to HRSA. These results are also reflected in sex-related differences in proliferative responses of the HRSA-non-adherent mononuclear cell population to T cell-dependent mitogens antigens and allogeneic mononuclear cells.", "contents": "Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females. An attempt was made to investigate the possible existence of differences in the composition of peripheral blood lymphocytes between males and females. Using affinity chromatography of human peripheral mononuclear cells on insolubilized histamine together with staining by fluoresceinated histamine-rabbit serum albumin (HRSA) we revealed that males possess a significantly higher proportion of mononuclear cells which bind to HRSA. These results are also reflected in sex-related differences in proliferative responses of the HRSA-non-adherent mononuclear cell population to T cell-dependent mitogens antigens and allogeneic mononuclear cells."} {"id": "PMID:160850", "title": "Functional studies on T cells in adult human bone marrow.", "content": "Bone marrow (BM) lymphocytes were obtained by sucrose density gradient centrifugation of the nucleated cells from adult human BM. BM was obtained from rib sections removed routinely during thoracotomy from thirteen patients with a localized lung tumour and from two other patients without tumour (mean age 47 years). The percentage of T cells in BM was high (mean +/- s.d. 27% +/- 17) and increased with age. In eight cases, the function of isolated BM T cells was studied and compared to that of peripheral blood (PB) T cells. BM t cells showed poor helper activity for pokeweed mitogen (PWM) induced Ig production by PB non-T cells, which did not appear to be due to excessive suppressor cell activity. Phytohaemagglutinin (PHA) induced thymidine incorporation was only slightly decreased but peak values were only reached after 6 years, in contrast to 4 days for PB T cells. This delay did not seem to be due to a lack of monocytes. PHA, however, failed to induce cytotoxic activity in BM T cells. PWM-induced thymidine incorporation and responder capacity in the mixed lymphocyte reaction were also very poor. These results are interpreted as suggesting that many of the T cells in adult human marrow are immature.", "contents": "Functional studies on T cells in adult human bone marrow. Bone marrow (BM) lymphocytes were obtained by sucrose density gradient centrifugation of the nucleated cells from adult human BM. BM was obtained from rib sections removed routinely during thoracotomy from thirteen patients with a localized lung tumour and from two other patients without tumour (mean age 47 years). The percentage of T cells in BM was high (mean +/- s.d. 27% +/- 17) and increased with age. In eight cases, the function of isolated BM T cells was studied and compared to that of peripheral blood (PB) T cells. BM t cells showed poor helper activity for pokeweed mitogen (PWM) induced Ig production by PB non-T cells, which did not appear to be due to excessive suppressor cell activity. Phytohaemagglutinin (PHA) induced thymidine incorporation was only slightly decreased but peak values were only reached after 6 years, in contrast to 4 days for PB T cells. This delay did not seem to be due to a lack of monocytes. PHA, however, failed to induce cytotoxic activity in BM T cells. PWM-induced thymidine incorporation and responder capacity in the mixed lymphocyte reaction were also very poor. These results are interpreted as suggesting that many of the T cells in adult human marrow are immature."} {"id": "PMID:160845", "title": "Sound and the visually handicapped baby.", "content": "The part played by vision in learning to interpret both speech and environmental sounds and to localize the latter is discussed in the light of observations of the development of sighted and of blind babies. Subsequently, some suggestions of guidance strategies based on these observations, are put forward to help visually handicapped babies acquire localization skills. Preliminary experience using these techniques has been promising and they are being further developed and researched at The Wolfson Centre in London.", "contents": "Sound and the visually handicapped baby. The part played by vision in learning to interpret both speech and environmental sounds and to localize the latter is discussed in the light of observations of the development of sighted and of blind babies. Subsequently, some suggestions of guidance strategies based on these observations, are put forward to help visually handicapped babies acquire localization skills. Preliminary experience using these techniques has been promising and they are being further developed and researched at The Wolfson Centre in London."} {"id": "PMID:160851", "title": "Activation of human lymphocytes by supernatants from human thymic epithelium.", "content": "Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS.", "contents": "Activation of human lymphocytes by supernatants from human thymic epithelium. Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS."} {"id": "PMID:160852", "title": "Role of dialysis in the treatment of severe hypercalcemia: report of two cases successfully treated with hemodialysis and review of the literature.", "content": "The role of dialysis in the treatment of patients with severe hypercalcemia is uncertain. The fourteen previously reported cases of hypercalcemia treated with either peritoneal or hemodialysis have been reviewed. Two additional patients treated with hemodialysis are described in this report. Because the use of large volumes of intravenous fluids was contraindicated, each of the patients received a low calcium bath (0-1 mEq calcium per liter) hemodialysis for three and a half hours. After dialysis, the serum calcium fell to normal in both and remained normal thereafter with treatment of the underlying disease (multiple myeloma in one and vitamin D intoxication in the other). Hemodialysis can clear up to 682 mg of calcium per hour as compared to 124 mg per hour for peritoneal dialysis and 82 mg per hour with forced saline diuresis. Low calcium bath hemodialysis is indicated when the presence of renal and/or cardiac failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients.", "contents": "Role of dialysis in the treatment of severe hypercalcemia: report of two cases successfully treated with hemodialysis and review of the literature. The role of dialysis in the treatment of patients with severe hypercalcemia is uncertain. The fourteen previously reported cases of hypercalcemia treated with either peritoneal or hemodialysis have been reviewed. Two additional patients treated with hemodialysis are described in this report. Because the use of large volumes of intravenous fluids was contraindicated, each of the patients received a low calcium bath (0-1 mEq calcium per liter) hemodialysis for three and a half hours. After dialysis, the serum calcium fell to normal in both and remained normal thereafter with treatment of the underlying disease (multiple myeloma in one and vitamin D intoxication in the other). Hemodialysis can clear up to 682 mg of calcium per hour as compared to 124 mg per hour for peritoneal dialysis and 82 mg per hour with forced saline diuresis. Low calcium bath hemodialysis is indicated when the presence of renal and/or cardiac failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients."} {"id": "PMID:160854", "title": "Contact allergy to hydrocortisone 17-butyrate.", "content": "Two female patients with stasis dermatitis developed allergic contact dermatitis to hydrocortisone 17-butyrate cream. Patch tests with hydrocortisone 17-butyrate were positive, but not with the vehicle. One patient was also allergic to two other commerical corticosteroids, but patch tests revealed positive reactions only to ingredients of the vehicles. Attention is drawn to the frequency of contact allergy to corticosteroids in patients with stasis dermatitis.", "contents": "Contact allergy to hydrocortisone 17-butyrate. Two female patients with stasis dermatitis developed allergic contact dermatitis to hydrocortisone 17-butyrate cream. Patch tests with hydrocortisone 17-butyrate were positive, but not with the vehicle. One patient was also allergic to two other commerical corticosteroids, but patch tests revealed positive reactions only to ingredients of the vehicles. Attention is drawn to the frequency of contact allergy to corticosteroids in patients with stasis dermatitis."} {"id": "PMID:160855", "title": "Dimethylthiourea, an unexpected hazard for textile workers.", "content": "Our patient was a 24-year-old female textile cutter who had a conjunctivitis and an erythematous itching dermatitis of the eyelids, nasal mucous membranes, and the corners of the mouth. The patch tests with the standard series and a pharmaceutical test battery were negative. Further epicutaneous testing revealed a strong positive reaction to the textile cutting patterns she handled, which were duplicated by diazo processing. Specifically, the contact dermatitis reaction was caused by dimethylthiourea, an additive in diazo-sensitized paper.", "contents": "Dimethylthiourea, an unexpected hazard for textile workers. Our patient was a 24-year-old female textile cutter who had a conjunctivitis and an erythematous itching dermatitis of the eyelids, nasal mucous membranes, and the corners of the mouth. The patch tests with the standard series and a pharmaceutical test battery were negative. Further epicutaneous testing revealed a strong positive reaction to the textile cutting patterns she handled, which were duplicated by diazo processing. Specifically, the contact dermatitis reaction was caused by dimethylthiourea, an additive in diazo-sensitized paper."} {"id": "PMID:160856", "title": "Nickel, cobalt and chromium sensitivity in patients with pompholyx (dyshidrotic eczema).", "content": "Sixteen patients with negative routine patch tests were challenged orally in a controlled trial with 2.5 mg nickel, 1 mg cobalt, and 2.5 mg chromium given as salts of the respective metals. All of the patients had symmetrical, vesicular hand dermatitis and in some cases also foot involvement. The dermatitis of two patients flared after challenge with cobalt; in two patients flare occurred following chromate ingestion. Prior to the oral challenge all the patients were patch tested with nickel sulphate, cobalt chloride and potassium dichromate after adhesive tape stripping. Solutions of the same metal salts were used for intradermal testing. The intradermal test sites were read after 20 minutes and 48 hours, the patch tests after 48 h. Skin test reactivity correlated poorly to the results of the oral challenge, possibly due to nonspecific skin test reactivity. It is concluded that oral challenge is a valuable adjunctive diagnostic procedure in patients with pompholyx who have negative routine patch tests.", "contents": "Nickel, cobalt and chromium sensitivity in patients with pompholyx (dyshidrotic eczema). Sixteen patients with negative routine patch tests were challenged orally in a controlled trial with 2.5 mg nickel, 1 mg cobalt, and 2.5 mg chromium given as salts of the respective metals. All of the patients had symmetrical, vesicular hand dermatitis and in some cases also foot involvement. The dermatitis of two patients flared after challenge with cobalt; in two patients flare occurred following chromate ingestion. Prior to the oral challenge all the patients were patch tested with nickel sulphate, cobalt chloride and potassium dichromate after adhesive tape stripping. Solutions of the same metal salts were used for intradermal testing. The intradermal test sites were read after 20 minutes and 48 hours, the patch tests after 48 h. Skin test reactivity correlated poorly to the results of the oral challenge, possibly due to nonspecific skin test reactivity. It is concluded that oral challenge is a valuable adjunctive diagnostic procedure in patients with pompholyx who have negative routine patch tests."} {"id": "PMID:160861", "title": "Macroscopic and microscopic studies of fallopian tube after laparoscopic sterilization.", "content": "Histological study was carried out on human fallopian tubes one hour and one month after various methods of laparoscopic sterilization. Ciliated cells were counted and histological lesions were observed. Deciliation is proved at a distance from the site of sterilization. Taking into account these two data, it has been possible to display the substance loss provoked by each of the usual sterilization methods (unipolar electro-coagulation, bipolar electrocoagulation, silicone ring and Hulka-Clements clip) which have to be taken into consideration in case of surgical re-anastomosis.", "contents": "Macroscopic and microscopic studies of fallopian tube after laparoscopic sterilization. Histological study was carried out on human fallopian tubes one hour and one month after various methods of laparoscopic sterilization. Ciliated cells were counted and histological lesions were observed. Deciliation is proved at a distance from the site of sterilization. Taking into account these two data, it has been possible to display the substance loss provoked by each of the usual sterilization methods (unipolar electro-coagulation, bipolar electrocoagulation, silicone ring and Hulka-Clements clip) which have to be taken into consideration in case of surgical re-anastomosis."} {"id": "PMID:160860", "title": "The probability of side effects with ovral, norinyl 1/50 and norlestrin.", "content": "This report provides specific information on the prevalence rates of the most common side effects during the first 3 cycles of use of 3 combination oral contraceptives (OCs) containing 50 mcg estrogen. The probabilities of a symptom occurring for the first time, or persisting once present, during the initial cycles of OC use are given for each of the 3 combined OCs.", "contents": "The probability of side effects with ovral, norinyl 1/50 and norlestrin. This report provides specific information on the prevalence rates of the most common side effects during the first 3 cycles of use of 3 combination oral contraceptives (OCs) containing 50 mcg estrogen. The probabilities of a symptom occurring for the first time, or persisting once present, during the initial cycles of OC use are given for each of the 3 combined OCs."} {"id": "PMID:160868", "title": "Down syndrome: prevalence at birth, mortality and survival. A 17-year study.", "content": "Analysis of comprehensive records over a period of 15 yr permits calculation of the total prevalence of Down Syndrome in an industrial city. The prevalence at birth is shown to have fallen from 1.70 per 1000 births in the period 1961--65 to 0.84 per 1000 births in 1971--75. The fall in prevalence can be shown to be largely due to a change in distribution of maternal age. An earlier increase in the number of Down Syndrome children is shown to reflect a greatly improved survival in the first 5 yr of life to a continuing level of 81%. The number of Down Syndrome children is unlikely to increase much even with increase of birth rate unless older mothers have further pregnancies. For these reasons the policies of amniocentesis of older women and termination of affected pregnancies will have progressively less effect on the number of affected children if this demographic trend continues. A further effect is that special schools will have a proportionately greater burden as the younger children being admitted have less prospect of development and may be more demanding of staff than Down Syndrome children.", "contents": "Down syndrome: prevalence at birth, mortality and survival. A 17-year study. Analysis of comprehensive records over a period of 15 yr permits calculation of the total prevalence of Down Syndrome in an industrial city. The prevalence at birth is shown to have fallen from 1.70 per 1000 births in the period 1961--65 to 0.84 per 1000 births in 1971--75. The fall in prevalence can be shown to be largely due to a change in distribution of maternal age. An earlier increase in the number of Down Syndrome children is shown to reflect a greatly improved survival in the first 5 yr of life to a continuing level of 81%. The number of Down Syndrome children is unlikely to increase much even with increase of birth rate unless older mothers have further pregnancies. For these reasons the policies of amniocentesis of older women and termination of affected pregnancies will have progressively less effect on the number of affected children if this demographic trend continues. A further effect is that special schools will have a proportionately greater burden as the younger children being admitted have less prospect of development and may be more demanding of staff than Down Syndrome children."} {"id": "PMID:160869", "title": "The epidemiology of severe mental handicap.", "content": "Prevalence studies of severe mental handicap in an industrial area in the North West area of the United Kingdom have shown a marked increase between 1961 and 1977, with the hint of a reduction in the most recent years. Further analysis of causes of severe mental handicap shows that the prevalence of Down Syndrome is decreasing, certain causes remain constant in prevalence, and perinatal metabolic causes are shown to be increasing through a period of 15 yr ending in 1975. While improved survival of children influences the total prevalence, high mortality in some conditions makes the analysis of prevalence at birth more significant in considering changes in the pattern of aetiology. These studies are fundamental to the formulation of policies of prevention of severe mental handicap, whether these be social or dependent solely on health care services.", "contents": "The epidemiology of severe mental handicap. Prevalence studies of severe mental handicap in an industrial area in the North West area of the United Kingdom have shown a marked increase between 1961 and 1977, with the hint of a reduction in the most recent years. Further analysis of causes of severe mental handicap shows that the prevalence of Down Syndrome is decreasing, certain causes remain constant in prevalence, and perinatal metabolic causes are shown to be increasing through a period of 15 yr ending in 1975. While improved survival of children influences the total prevalence, high mortality in some conditions makes the analysis of prevalence at birth more significant in considering changes in the pattern of aetiology. These studies are fundamental to the formulation of policies of prevention of severe mental handicap, whether these be social or dependent solely on health care services."} {"id": "PMID:160870", "title": "Effect of calcitonin on Ca-ATPase activity of plasma membrane in liver of rats.", "content": "The effect of calcitonin (CT) on Ca-ATPase activity in the plasma membrane fraction of rat liver was investigated. CT (80 MRC mU/100 g BW) administered subcutaneously to rats, caused a significant decrease in serum calcium, while increasing liver calcium. The administration of CT produced a rapid decrease of Ca-ATPase activity in the plasma membrane fraction of liver, whereas CT did not cause a significant alteration of p-nitrophenyl phosphatase activity. The maximal response of CT was obtained with 80 MRC mU/100 g BW. Meanwhile, the administration of imidazole (30 mg/100 g BW) which has a hypocalcemic effect, like CT, produced a significant increase in liver calcium and a corresponding fall in Ca-ATPase activity of the plasma membrane fraction. The reduction of Ca-ATPase activity produced by imidazole was significantly potentiated by the simultaneous administration of CT, and the rise in liver calcium was enhanced slightly. The present results suggest that the action of CT on liver calcium involves the decrease of Ca-ATPase activity in the plasma membrane of rat liver.", "contents": "Effect of calcitonin on Ca-ATPase activity of plasma membrane in liver of rats. The effect of calcitonin (CT) on Ca-ATPase activity in the plasma membrane fraction of rat liver was investigated. CT (80 MRC mU/100 g BW) administered subcutaneously to rats, caused a significant decrease in serum calcium, while increasing liver calcium. The administration of CT produced a rapid decrease of Ca-ATPase activity in the plasma membrane fraction of liver, whereas CT did not cause a significant alteration of p-nitrophenyl phosphatase activity. The maximal response of CT was obtained with 80 MRC mU/100 g BW. Meanwhile, the administration of imidazole (30 mg/100 g BW) which has a hypocalcemic effect, like CT, produced a significant increase in liver calcium and a corresponding fall in Ca-ATPase activity of the plasma membrane fraction. The reduction of Ca-ATPase activity produced by imidazole was significantly potentiated by the simultaneous administration of CT, and the rise in liver calcium was enhanced slightly. The present results suggest that the action of CT on liver calcium involves the decrease of Ca-ATPase activity in the plasma membrane of rat liver."} {"id": "PMID:160866", "title": "Role of serotonin in tolerance to ethanol and barbiturates: evidence for a specific vs. non-specific concept of tolerance.", "content": "The results of our recent investigations have suggested that tolerance and cross-tolerance development to motor-impairing and hypothermic effects of ethanol was slowed when brain serotonin (5-HT) was extensively depleted by treatment with p-chlorophenylalanine (p-CPA). These findings have been extended by the observation that p-PCA also slowed the development of tolerance to motor-impairing effects of barbital whether tolerance was tested repeatedly in the same animal or in separate subgroups being tested only once. Additional support was provided by the demonstration that intracerebral injection of 5,7-dihydroxytryptamine (-DHT), which is known to deplete 5-HT markedly, also slowed the development of tolerance to motor-impairing and hypothermic effects of ethanol. In addition, when brain 5-HT level was elevated by administration of L-tryptophan, the rate of tolerance development to ethanol, as measured by motor impairment and hypothermia, was accelerated. In contrast to 5,7-DHT, intracerebral injection of 5,6-DHT was surprisingly found to accelerate the development of tolerance to ethanol. Upon further investigation, however, it was determined that the 5,6-DHT treatment depleted brain 5-HT levels by only 20% and, in addition, resulted in the development of supersensitivity. These results further confirm and extend the generality of our observations that 5-HT may be involved in the development of tolerance and cross-tolerance to sedatives. The possibility of a non-specific vs. specific effect of the serotoninergic system (as well as other aminergic systems) in tolerance and neuroplasticity deserves further investigation. The possible significance of these findings and the role of 5-HT (and noradrenaline) in the mechanism of tolerance are discussed in terms of analogy to enzyme or receptor mechanism.", "contents": "Role of serotonin in tolerance to ethanol and barbiturates: evidence for a specific vs. non-specific concept of tolerance. The results of our recent investigations have suggested that tolerance and cross-tolerance development to motor-impairing and hypothermic effects of ethanol was slowed when brain serotonin (5-HT) was extensively depleted by treatment with p-chlorophenylalanine (p-CPA). These findings have been extended by the observation that p-PCA also slowed the development of tolerance to motor-impairing effects of barbital whether tolerance was tested repeatedly in the same animal or in separate subgroups being tested only once. Additional support was provided by the demonstration that intracerebral injection of 5,7-dihydroxytryptamine (-DHT), which is known to deplete 5-HT markedly, also slowed the development of tolerance to motor-impairing and hypothermic effects of ethanol. In addition, when brain 5-HT level was elevated by administration of L-tryptophan, the rate of tolerance development to ethanol, as measured by motor impairment and hypothermia, was accelerated. In contrast to 5,7-DHT, intracerebral injection of 5,6-DHT was surprisingly found to accelerate the development of tolerance to ethanol. Upon further investigation, however, it was determined that the 5,6-DHT treatment depleted brain 5-HT levels by only 20% and, in addition, resulted in the development of supersensitivity. These results further confirm and extend the generality of our observations that 5-HT may be involved in the development of tolerance and cross-tolerance to sedatives. The possibility of a non-specific vs. specific effect of the serotoninergic system (as well as other aminergic systems) in tolerance and neuroplasticity deserves further investigation. The possible significance of these findings and the role of 5-HT (and noradrenaline) in the mechanism of tolerance are discussed in terms of analogy to enzyme or receptor mechanism."} {"id": "PMID:160872", "title": "[Establishment of a colony of Japanese white rabbits free from coccidia and their breeding performance (author's transl)].", "content": "A colony of rabbits free from coccidia was established in 1974 by weaning young at 25 days of age from dams infected with coccidia. Until now Bordetella, Pasteurella and Psoroptes cuniculi have not been detected either, and neither diarrhea nor death has occurred in weanlings of the colony. However, the mortality of sucklings was significantly high owing to cannibalism and tread by their dams. The weaning rate was effectively improved by use of a large nursing cage (3,100 cm2) and sterilized hay on a stainless steel mesh floor of the nursing cage.", "contents": "[Establishment of a colony of Japanese white rabbits free from coccidia and their breeding performance (author's transl)]. A colony of rabbits free from coccidia was established in 1974 by weaning young at 25 days of age from dams infected with coccidia. Until now Bordetella, Pasteurella and Psoroptes cuniculi have not been detected either, and neither diarrhea nor death has occurred in weanlings of the colony. However, the mortality of sucklings was significantly high owing to cannibalism and tread by their dams. The weaning rate was effectively improved by use of a large nursing cage (3,100 cm2) and sterilized hay on a stainless steel mesh floor of the nursing cage."} {"id": "PMID:160886", "title": "[Induction of tolerance by the intrathymic injection of antigen in mice (author's transl)].", "content": "Immunological tolerance can be easily introduced in mice by a direct injection of antigen into the thymus. Comparing the efficiency of tolerance induction by intrathymic injection of antigen with that by intravenous one, the former has proved to be far more superior than the latter, and the state of tolerance brought about by the former was more complete than that by the latter. One of the reasons why the intrathymic injection of antigen is an useful means for tolerance induction is considered to be ascribable to the appearance of large amount of suppressor T cells stimulated by the direct contact of antigen and thymocytes, the evidence of which being shown in the present study.", "contents": "[Induction of tolerance by the intrathymic injection of antigen in mice (author's transl)]. Immunological tolerance can be easily introduced in mice by a direct injection of antigen into the thymus. Comparing the efficiency of tolerance induction by intrathymic injection of antigen with that by intravenous one, the former has proved to be far more superior than the latter, and the state of tolerance brought about by the former was more complete than that by the latter. One of the reasons why the intrathymic injection of antigen is an useful means for tolerance induction is considered to be ascribable to the appearance of large amount of suppressor T cells stimulated by the direct contact of antigen and thymocytes, the evidence of which being shown in the present study."} {"id": "PMID:160887", "title": "Herpetic keratitis in athymic (nude) mice.", "content": "The inflammatory response to herpes simplex virus infection of the cornea was studied in athymic nude (nu/nu) and heterozygote (nu/+) BALB/c mice. Although athymic mice were highly susceptible to HSV infection and died 13 to 17 days after corneal inoculation, they failed to develop necrotizing keratitis of the cornea. Heterozygote mice survived the initial virual infection, but many of these mice developed necrotizing keratitis and permanent corneal scarring. Light and electron microscopy showed numerous inflammatory cells (polymorphonuclear leukocytes and lymphocytes) in the corneas of heterozygote mice, but not in the athymic mice. These studies suggest that the immune system plays a dual role in herpes simplex virus infection of the cornea: protection against dissemination of the virus and immunopathogenesis of necrotizing keratitis in the cornea.", "contents": "Herpetic keratitis in athymic (nude) mice. The inflammatory response to herpes simplex virus infection of the cornea was studied in athymic nude (nu/nu) and heterozygote (nu/+) BALB/c mice. Although athymic mice were highly susceptible to HSV infection and died 13 to 17 days after corneal inoculation, they failed to develop necrotizing keratitis of the cornea. Heterozygote mice survived the initial virual infection, but many of these mice developed necrotizing keratitis and permanent corneal scarring. Light and electron microscopy showed numerous inflammatory cells (polymorphonuclear leukocytes and lymphocytes) in the corneas of heterozygote mice, but not in the athymic mice. These studies suggest that the immune system plays a dual role in herpes simplex virus infection of the cornea: protection against dissemination of the virus and immunopathogenesis of necrotizing keratitis in the cornea."} {"id": "PMID:160888", "title": "Susceptibility to adjuvant-induced arthritis among germfree, specific-pathogen-free, and conventional rats.", "content": "Germfree F344 rats developed severe arthritis with 100% incidence after a single intradermal inection of either squalane containing 0.5 mg of heat-killed Mycobacterium bovis BCG or a water-in-oil emulsion containing 0.2 mg of peptidoglycan derived from Staphylococcus epidermidis. Conventional F344 rats developed less-severe arthritis with 20% incidence for heat-killed BCG and 0% incidence for peptidoglycan. Specific-pathogen-free rats showed an intermediate susceptibility between germfree and conventional rats. Interestingly, both unimmunized specific-pathogen-free and conventional rats. but not unimmunized germfree rats, showed weak delayed-type hypersensitivity reactions to peptidoglycans derived from either S. epidermidis or Lactobacillus plantarum, suggesting that a bacterial flora may furnish a stimulus for induction of cell-mediated immunity to ubiquitous bacterial peptidoglycans. It is thus possible that although a bacterial flora is not necessary for development of adjuvant arthritis, it may have some suppressive effect on the development of the disease in specific-pathogen-free and conventional F344 rats, possibly through modulation of the immune response.", "contents": "Susceptibility to adjuvant-induced arthritis among germfree, specific-pathogen-free, and conventional rats. Germfree F344 rats developed severe arthritis with 100% incidence after a single intradermal inection of either squalane containing 0.5 mg of heat-killed Mycobacterium bovis BCG or a water-in-oil emulsion containing 0.2 mg of peptidoglycan derived from Staphylococcus epidermidis. Conventional F344 rats developed less-severe arthritis with 20% incidence for heat-killed BCG and 0% incidence for peptidoglycan. Specific-pathogen-free rats showed an intermediate susceptibility between germfree and conventional rats. Interestingly, both unimmunized specific-pathogen-free and conventional rats. but not unimmunized germfree rats, showed weak delayed-type hypersensitivity reactions to peptidoglycans derived from either S. epidermidis or Lactobacillus plantarum, suggesting that a bacterial flora may furnish a stimulus for induction of cell-mediated immunity to ubiquitous bacterial peptidoglycans. It is thus possible that although a bacterial flora is not necessary for development of adjuvant arthritis, it may have some suppressive effect on the development of the disease in specific-pathogen-free and conventional F344 rats, possibly through modulation of the immune response."} {"id": "PMID:160889", "title": "Comparison of natural killer cells induced by Kunjin virus and Corynebacterium parvum with those occurring naturally in nude mice.", "content": "Natural killer (NK) cells are rapidly elicited in the spleen and peritoneal cavity of mice inoculated intravenously or intraperitoneally with live Kunjin virus, and more slowly in the peritoneal cavity of mice inoculated intraperitoneally with Formalin-inactivated Corynebacterium parvum. NK cells induced by either agent display cytotoxicity for a similar spectrum of syngeneic, allogeneic, and xenogeneic cultured cell lines. By contrast, the cells occurring naturally in the spleen of congenitally athymic (nude) mice show substantially lower NK activity and are cytotoxic for a more restricted range of target cell lines. The distinction suggests that there may be more than one type of NK cell or that activation enhances the cytotoxicity and perhaps broadens the range of target specificity of endogenous NK cells.", "contents": "Comparison of natural killer cells induced by Kunjin virus and Corynebacterium parvum with those occurring naturally in nude mice. Natural killer (NK) cells are rapidly elicited in the spleen and peritoneal cavity of mice inoculated intravenously or intraperitoneally with live Kunjin virus, and more slowly in the peritoneal cavity of mice inoculated intraperitoneally with Formalin-inactivated Corynebacterium parvum. NK cells induced by either agent display cytotoxicity for a similar spectrum of syngeneic, allogeneic, and xenogeneic cultured cell lines. By contrast, the cells occurring naturally in the spleen of congenitally athymic (nude) mice show substantially lower NK activity and are cytotoxic for a more restricted range of target cell lines. The distinction suggests that there may be more than one type of NK cell or that activation enhances the cytotoxicity and perhaps broadens the range of target specificity of endogenous NK cells."} {"id": "PMID:160890", "title": "Chemical analysis of changes in membrane composition during growth of Streptococcus pyogenes.", "content": "Changes in the structural components of the Streptococcus pyogenes membrane between exponential and early stationary phases of growth are reported. The overall protein composition ranged from 70 to 73% of the dry weight of the membranes, irrespective of the phase of growth from which they were isolated. Amino acid analyses of membranes isolated from streptococci in either the exponential or stationary phase of growth demonstrated that two amino acids, cysteine and tryptophan, were absent. Further analysis of the membrane proteins by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis demonstrated that there were proteins unique to a particular phase of growth as well as differences in the amount of specific proteins from the various growth phases. In addition, membranes isolated from exponential-phase cultures contained a higher percentage of peripheral protein than did stationary-phase membranes. There also appeared to be an increase in the amount of outer surface proteins during this growth phase. The phosphorus content of the membranes increased during the stationary phase of growth, whereas the sugar composition remained constant. The only sugar found under various conditions of growth in any of the strains was glucose. Total fatty acid content and the mole percent composition of various fatty acids did not change in the different phases of growth. However, the mole percent composition of fatty acids in the membranes of various group A streptococci did differ between strains. Therefore, these results provide evidence that the composition of membranes of S. pyogenes does not remain constant throughout the growth phases of the culture.", "contents": "Chemical analysis of changes in membrane composition during growth of Streptococcus pyogenes. Changes in the structural components of the Streptococcus pyogenes membrane between exponential and early stationary phases of growth are reported. The overall protein composition ranged from 70 to 73% of the dry weight of the membranes, irrespective of the phase of growth from which they were isolated. Amino acid analyses of membranes isolated from streptococci in either the exponential or stationary phase of growth demonstrated that two amino acids, cysteine and tryptophan, were absent. Further analysis of the membrane proteins by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis demonstrated that there were proteins unique to a particular phase of growth as well as differences in the amount of specific proteins from the various growth phases. In addition, membranes isolated from exponential-phase cultures contained a higher percentage of peripheral protein than did stationary-phase membranes. There also appeared to be an increase in the amount of outer surface proteins during this growth phase. The phosphorus content of the membranes increased during the stationary phase of growth, whereas the sugar composition remained constant. The only sugar found under various conditions of growth in any of the strains was glucose. Total fatty acid content and the mole percent composition of various fatty acids did not change in the different phases of growth. However, the mole percent composition of fatty acids in the membranes of various group A streptococci did differ between strains. Therefore, these results provide evidence that the composition of membranes of S. pyogenes does not remain constant throughout the growth phases of the culture."} {"id": "PMID:160891", "title": "Quantitative immunoelectrophoretic analysis of Streptococcus pyogenes membrane.", "content": "The antigenic composition and molecular structure of the plasma membrane of Streptococcus pyogenes (group A; M type 6) were studied by crossed immunoelectrophoresis (XIE) and other related quantitative immunoelectrophoretic techniques. After establishment of a reference pattern of 29 immunoprecipitates, the relative differences in amounts of individual antigens contained in membranes isolated from cells that were harvested during the exponential or stationary phase of growth were examined. Relative increases and decreases in amounts of individual antigens were estimated from the areas subtended by immunoprecipitates after XIE of Triton X-100 extracts. The asymmetric distribution of antigens on the inner and outer surfaces of the membrane was established in absorption experiments with intact, stable protoplasts. Of the 29 immunoprecipitates, 8 appeared to contain antigens exposed on the outer surface of the membrane, whereas 11 appeared to contain antigens either located on the inner surface or unexposed. Six antigens appeared to have limited exposure on the outer surface, and four others remain to be assigned. Certain immunoprecipitates were characterized with respect to enzymatic activity or interaction with the lectin concanavalin A. Reduced nicotinamide adenine dinucleotide dehydrogenase (EC 1.6.99.3), adenosine triphosphatase (EC 3.6.1.3), and polynucleotide phosphorylase (EC 2.3.7.8) were demonstrated by zymogram techniques. The latter two activities were present within the same immunoprecipitate, suggesting the occurrence of a multienzyme complex. In addition, the areas under the immunoprecipitates containing the three enzymatic activities were not affected by absorption of antimembrane immunoglobulin with intact protoplasts and thus appeared to be located on the inner surface of the membrane. The results from absorption experiments also suggested that the exposure of outer protoplast surface antigens was greater on protoplasts from exponential-phase cells than on those from stationary-phase cells, even when found in increased amounts in the latter.", "contents": "Quantitative immunoelectrophoretic analysis of Streptococcus pyogenes membrane. The antigenic composition and molecular structure of the plasma membrane of Streptococcus pyogenes (group A; M type 6) were studied by crossed immunoelectrophoresis (XIE) and other related quantitative immunoelectrophoretic techniques. After establishment of a reference pattern of 29 immunoprecipitates, the relative differences in amounts of individual antigens contained in membranes isolated from cells that were harvested during the exponential or stationary phase of growth were examined. Relative increases and decreases in amounts of individual antigens were estimated from the areas subtended by immunoprecipitates after XIE of Triton X-100 extracts. The asymmetric distribution of antigens on the inner and outer surfaces of the membrane was established in absorption experiments with intact, stable protoplasts. Of the 29 immunoprecipitates, 8 appeared to contain antigens exposed on the outer surface of the membrane, whereas 11 appeared to contain antigens either located on the inner surface or unexposed. Six antigens appeared to have limited exposure on the outer surface, and four others remain to be assigned. Certain immunoprecipitates were characterized with respect to enzymatic activity or interaction with the lectin concanavalin A. Reduced nicotinamide adenine dinucleotide dehydrogenase (EC 1.6.99.3), adenosine triphosphatase (EC 3.6.1.3), and polynucleotide phosphorylase (EC 2.3.7.8) were demonstrated by zymogram techniques. The latter two activities were present within the same immunoprecipitate, suggesting the occurrence of a multienzyme complex. In addition, the areas under the immunoprecipitates containing the three enzymatic activities were not affected by absorption of antimembrane immunoglobulin with intact protoplasts and thus appeared to be located on the inner surface of the membrane. The results from absorption experiments also suggested that the exposure of outer protoplast surface antigens was greater on protoplasts from exponential-phase cells than on those from stationary-phase cells, even when found in increased amounts in the latter."} {"id": "PMID:160892", "title": "Novel iron uptake system specified by ColV plasmids: an important component in the virulence of invasive strains of Escherichia coli.", "content": "The enhanced virulence of invasive strains of Escherichia coli carrying ColV plasmids was shown to be due to a novel plasmid-mediated iron uptake system. Possession of a ColV plasmid conferred strong selective advantage on the host bacterial strain in experimental infections unless excess iron was administered in the inoculum. Moreover, supplementation of defined minimal medium with transferrin to complex available iron caused marked limitation of the growth of plasmid-free strains but had no effect on strains carrying a ColV plasmid. The activity of an efficient iron uptake process was clearly shown by experiments with a mutant of E. coli deficient in enterochelin biosynthesis. Although the mutant was dependent on the presence of citrate in the growth medium to facilitate iron transport, colicinogenic derivatives did not require added citrate for growth. Radioactive iron was shown to be taken up rapidly by nongrowing cells of the plasmid-carrying strain. Furthermore, it was observed that repression of the synthesis of specific outer membrane proteins normally induced by conditions of iron deficit was maintained after a shift of the colicinogenic strains from a rich medium to a medium low in iron. The ColV plasmid-mediated iron uptake system was independent of the active iron transport mechanisms known in E. coli, but like them it required tonB activity as a source of energy.", "contents": "Novel iron uptake system specified by ColV plasmids: an important component in the virulence of invasive strains of Escherichia coli. The enhanced virulence of invasive strains of Escherichia coli carrying ColV plasmids was shown to be due to a novel plasmid-mediated iron uptake system. Possession of a ColV plasmid conferred strong selective advantage on the host bacterial strain in experimental infections unless excess iron was administered in the inoculum. Moreover, supplementation of defined minimal medium with transferrin to complex available iron caused marked limitation of the growth of plasmid-free strains but had no effect on strains carrying a ColV plasmid. The activity of an efficient iron uptake process was clearly shown by experiments with a mutant of E. coli deficient in enterochelin biosynthesis. Although the mutant was dependent on the presence of citrate in the growth medium to facilitate iron transport, colicinogenic derivatives did not require added citrate for growth. Radioactive iron was shown to be taken up rapidly by nongrowing cells of the plasmid-carrying strain. Furthermore, it was observed that repression of the synthesis of specific outer membrane proteins normally induced by conditions of iron deficit was maintained after a shift of the colicinogenic strains from a rich medium to a medium low in iron. The ColV plasmid-mediated iron uptake system was independent of the active iron transport mechanisms known in E. coli, but like them it required tonB activity as a source of energy."} {"id": "PMID:160893", "title": "Models for study of the specificity by which indigenous lactobacilli adhere to murine gastric epithelia.", "content": "A Lactobacillus strain isolated from a mouse (indigenous) and another strain isolated from swine feces (nonindigenous) were compared in two model systems for their ability to adhere in vitro and in vivo to keratinizing squamous and columnar epithelia of mouse stomachs. In one model, stomachs dissected from specific-pathogen-free or germfree mice were injected with suspensions of lactobacilli labeled with [(3)H]thymidine and incubated at 37 degrees C. Thereafter, the non-secreting and secreting tissues were separated and washed vigorously. The radioactivity remaining with each tissue was counted by liquid scintillation spectrometry. When the radioactivity remaining with these tissues ranged between 500 and 100,000 cpm, the calculated radioactivity (disintegrations per minute) was related linearly to the number of lactobacilli adhering to the tissue. The estimate of the number of bacteria adherent to the tissue was not influenced significantly by artifacts in the techniques used. In this model, both Lactobacillus strains adhered in equally high numbers to both types of epithelial surfaces from stomachs from germfree mice. In contrast, in the second model, in which germfree mice were monoassociated with one or the other of the Lactobacillus strains, only the strain indigenous to the mouse formed dense layers on the epithelia of the nonsecreting portions of the stomachs, although both strains maintained high population levels throughout the gastrointestinal tracts of the animals. The capacity to adhere to the mucosal surface is undoubtedly necessary for lactobacilli to colonize gastric epithelia in mice. Our findings suggest, however, that nutritional or environmental conditions dictate whether particular Lactobacillus strains can colonize particular surfaces in the stomachs of living animals.", "contents": "Models for study of the specificity by which indigenous lactobacilli adhere to murine gastric epithelia. A Lactobacillus strain isolated from a mouse (indigenous) and another strain isolated from swine feces (nonindigenous) were compared in two model systems for their ability to adhere in vitro and in vivo to keratinizing squamous and columnar epithelia of mouse stomachs. In one model, stomachs dissected from specific-pathogen-free or germfree mice were injected with suspensions of lactobacilli labeled with [(3)H]thymidine and incubated at 37 degrees C. Thereafter, the non-secreting and secreting tissues were separated and washed vigorously. The radioactivity remaining with each tissue was counted by liquid scintillation spectrometry. When the radioactivity remaining with these tissues ranged between 500 and 100,000 cpm, the calculated radioactivity (disintegrations per minute) was related linearly to the number of lactobacilli adhering to the tissue. The estimate of the number of bacteria adherent to the tissue was not influenced significantly by artifacts in the techniques used. In this model, both Lactobacillus strains adhered in equally high numbers to both types of epithelial surfaces from stomachs from germfree mice. In contrast, in the second model, in which germfree mice were monoassociated with one or the other of the Lactobacillus strains, only the strain indigenous to the mouse formed dense layers on the epithelia of the nonsecreting portions of the stomachs, although both strains maintained high population levels throughout the gastrointestinal tracts of the animals. The capacity to adhere to the mucosal surface is undoubtedly necessary for lactobacilli to colonize gastric epithelia in mice. Our findings suggest, however, that nutritional or environmental conditions dictate whether particular Lactobacillus strains can colonize particular surfaces in the stomachs of living animals."} {"id": "PMID:160894", "title": "Establishment and characterization of human B-lymphocytic lymphoma cell lines (BALM-3, -4 and -5); intraclonal variation in the B-cell differentiation stage.", "content": "This study describes the establishment of three non-Burkitt B-lymphoma cell lines (BALM-3, BALM-4 and BALM-5) originating from the pleural effusion of a patient with a poorly differentiated diffuse lymphocytic lymphoma. The cells of BALM-3, -4 and -5 exhibited a number of properties which distinguish them from the usual B-cell type lymphoblastoid cell lines. Thus, they lacked the Epstein-Barr virus genome and had abnormal chromosome constitutions including a 14q+ marker. The presence of the identical surface immunoglobulin isotypes (gamma and chi chain determinants), and Ia-like B-cell-associated antigen in the cultured cells and in the \"fresh\" lymphoma cells in vivo was demonstrated. These findings strongly suggested that these cell lines have B-cell characteristics and were derived from the original tumor cell population. BALM-5 cells, however, showed somewhat different growth, cell surface marker profile and functional characteristics compared to those of BALM-3, and -4 cells. These variations suggest that the BALM-5 cells were probably at different stages of B-cell maturation than those of BALM-3 and -4, even though all three cell lines (established in three separate flasks) originated from the cells of the same pleural effusion of a lymphoma with monoclonal B-cell characteristics.", "contents": "Establishment and characterization of human B-lymphocytic lymphoma cell lines (BALM-3, -4 and -5); intraclonal variation in the B-cell differentiation stage. This study describes the establishment of three non-Burkitt B-lymphoma cell lines (BALM-3, BALM-4 and BALM-5) originating from the pleural effusion of a patient with a poorly differentiated diffuse lymphocytic lymphoma. The cells of BALM-3, -4 and -5 exhibited a number of properties which distinguish them from the usual B-cell type lymphoblastoid cell lines. Thus, they lacked the Epstein-Barr virus genome and had abnormal chromosome constitutions including a 14q+ marker. The presence of the identical surface immunoglobulin isotypes (gamma and chi chain determinants), and Ia-like B-cell-associated antigen in the cultured cells and in the \"fresh\" lymphoma cells in vivo was demonstrated. These findings strongly suggested that these cell lines have B-cell characteristics and were derived from the original tumor cell population. BALM-5 cells, however, showed somewhat different growth, cell surface marker profile and functional characteristics compared to those of BALM-3, and -4 cells. These variations suggest that the BALM-5 cells were probably at different stages of B-cell maturation than those of BALM-3 and -4, even though all three cell lines (established in three separate flasks) originated from the cells of the same pleural effusion of a lymphoma with monoclonal B-cell characteristics."} {"id": "PMID:160896", "title": "Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.", "content": "In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.", "contents": "Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors. In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts."} {"id": "PMID:160897", "title": "Fixed drug eruption: a lesson in drug usage.", "content": "Fixed drug eruption, a common finding in Lagos, was observed among patients being treated with two heavily promoted drugs: a pyrazolone analgesic and a benzodiazepine. Offending drugs should be considered in general classes rather than as individual compounds.", "contents": "Fixed drug eruption: a lesson in drug usage. Fixed drug eruption, a common finding in Lagos, was observed among patients being treated with two heavily promoted drugs: a pyrazolone analgesic and a benzodiazepine. Offending drugs should be considered in general classes rather than as individual compounds."} {"id": "PMID:160898", "title": "New videodensitometric method for measuring renal artery blood flow at routine arteriography: validation in the canine model.", "content": "A contrast medium was injected in the aortic arch and selectively in a renal artery to estimate the renal blood flow as a percentage of the cardiac output by the videodensitometric (VD) method. Twenty-six paired VD measurements in four mongrel dogs were obtained and the results compared to electromagnetic (EM) flow readings from the aortic arch and a renal artery. The relative renal blood flow estimated by the VD method averaged 9.1% and correlated with the EM flow average of 9.6% with r = 0.96. Previous in vitro investigations of relative flow in a model have now been validated in vivo. These results suggest that videodensitometry could be a clinical tool for measuring renal blood flow in conjunction with routine arteriography.", "contents": "New videodensitometric method for measuring renal artery blood flow at routine arteriography: validation in the canine model. A contrast medium was injected in the aortic arch and selectively in a renal artery to estimate the renal blood flow as a percentage of the cardiac output by the videodensitometric (VD) method. Twenty-six paired VD measurements in four mongrel dogs were obtained and the results compared to electromagnetic (EM) flow readings from the aortic arch and a renal artery. The relative renal blood flow estimated by the VD method averaged 9.1% and correlated with the EM flow average of 9.6% with r = 0.96. Previous in vitro investigations of relative flow in a model have now been validated in vivo. These results suggest that videodensitometry could be a clinical tool for measuring renal blood flow in conjunction with routine arteriography."} {"id": "PMID:160908", "title": "Semiautomated method for niacin and niacinamide in food products: collaborative study.", "content": "A collaborative study was conducted comparing a semiautomated colorimetric niacin method with a manual colorimetric and a microbiological method for 10 food products. Seven laboratories used the microbiological method, 7 laboratories used the manual colorimetric method, and 6 laboratories used the semiautomated method. The semiautomated method was more repeatable within a laboratory and more reproducible between laboratories than was either of the other methods. The semiautomated method results compared favorably with both the microbiological and manual colorimetric method results.", "contents": "Semiautomated method for niacin and niacinamide in food products: collaborative study. A collaborative study was conducted comparing a semiautomated colorimetric niacin method with a manual colorimetric and a microbiological method for 10 food products. Seven laboratories used the microbiological method, 7 laboratories used the manual colorimetric method, and 6 laboratories used the semiautomated method. The semiautomated method was more repeatable within a laboratory and more reproducible between laboratories than was either of the other methods. The semiautomated method results compared favorably with both the microbiological and manual colorimetric method results."} {"id": "PMID:160909", "title": "High pressure liquid chromatographic determination of ochratoxin A and zearalenone in cereals.", "content": "A high pressure liquid chromatographic (HPLC) method has been developed for determining ochratoxin A and zearalenone in cereals. The sample is extracted with phosphoric acid and chloroform. The extract is cleaned by washing on a silica gel column with cyclohexane-ethylene dichloride-ethyl ether. After eluting zearalenone with chloroform, ochratoxin A is eluted with chloroform-formic acid. Zearalenone is extracted into alkaline solution, washed with chloroform, the pH is adjusted, and the zearalenone is extracted back into chloroform. Ochratoxin A is purified by chromatography on aqueous sodium biarbonate-Celite. The mycotoxins are determined by using a liquid chromatograph with 2 columns in series packed with Spherisorb ODS 10 micrometer and 5 micrometers, respectively. Ochratoxin A is detected with a speftrophotofluorometer, coupled in series with an ultra-violet detector for estimation of zearalenone. Detection limits are 1-5 micrograms/kg for ochratoxin A and 2 micrograms/kg for zearalenone.", "contents": "High pressure liquid chromatographic determination of ochratoxin A and zearalenone in cereals. A high pressure liquid chromatographic (HPLC) method has been developed for determining ochratoxin A and zearalenone in cereals. The sample is extracted with phosphoric acid and chloroform. The extract is cleaned by washing on a silica gel column with cyclohexane-ethylene dichloride-ethyl ether. After eluting zearalenone with chloroform, ochratoxin A is eluted with chloroform-formic acid. Zearalenone is extracted into alkaline solution, washed with chloroform, the pH is adjusted, and the zearalenone is extracted back into chloroform. Ochratoxin A is purified by chromatography on aqueous sodium biarbonate-Celite. The mycotoxins are determined by using a liquid chromatograph with 2 columns in series packed with Spherisorb ODS 10 micrometer and 5 micrometers, respectively. Ochratoxin A is detected with a speftrophotofluorometer, coupled in series with an ultra-violet detector for estimation of zearalenone. Detection limits are 1-5 micrograms/kg for ochratoxin A and 2 micrograms/kg for zearalenone."} {"id": "PMID:160910", "title": "Heavy meromyosin from skipjack tuna, Euthynus pelamis. Preparation and enzymic properties.", "content": "A method was developed to obtain heavy meromyosin (HMM) from the tryptic digest of skipjack tuna dorsal myosin. The tuna HMM thus obtained was shown to be homogeneous on gel filtration-gel electrophoresis, and on ultracentrifugation. The sedimentation constant (S20,w) was estimated to be 6.1S for tuna HMM. The ATPase activity of tuna dorsal HMM was found to be very similar to that of rabbit skeletal HMM in many respects: KCl concentration dependence, pH dependence, effect of pCMB, kinetic parameters (Vmax and Ka) in actin activation, and Arrhenius activation energy. The only difference found between tuna HMM and rabbit HMM was in heat denaturation behavior: the ATPase activities of tuna HMM were approximately four times as sensitive to heat inactivation as those of rabbit HMM. Thus, tuna HMM should represent a good experimental material for investigations of the molecular basis of susceptibility to denaturation, and of the characteristics of fish myosins in general. A new type of heat denaturation of myosin was observed. It occurred in a very early stage of heat treatment of either tuna dorsal myosin or rabbit skeletal myosin; however, it did not occur upon heat treatment of HMM of either tuna or rabbit, and it was detectable in terms of the Mg-ATPase activity only when the activity was measured in the presence of untreated actin.", "contents": "Heavy meromyosin from skipjack tuna, Euthynus pelamis. Preparation and enzymic properties. A method was developed to obtain heavy meromyosin (HMM) from the tryptic digest of skipjack tuna dorsal myosin. The tuna HMM thus obtained was shown to be homogeneous on gel filtration-gel electrophoresis, and on ultracentrifugation. The sedimentation constant (S20,w) was estimated to be 6.1S for tuna HMM. The ATPase activity of tuna dorsal HMM was found to be very similar to that of rabbit skeletal HMM in many respects: KCl concentration dependence, pH dependence, effect of pCMB, kinetic parameters (Vmax and Ka) in actin activation, and Arrhenius activation energy. The only difference found between tuna HMM and rabbit HMM was in heat denaturation behavior: the ATPase activities of tuna HMM were approximately four times as sensitive to heat inactivation as those of rabbit HMM. Thus, tuna HMM should represent a good experimental material for investigations of the molecular basis of susceptibility to denaturation, and of the characteristics of fish myosins in general. A new type of heat denaturation of myosin was observed. It occurred in a very early stage of heat treatment of either tuna dorsal myosin or rabbit skeletal myosin; however, it did not occur upon heat treatment of HMM of either tuna or rabbit, and it was detectable in terms of the Mg-ATPase activity only when the activity was measured in the presence of untreated actin."} {"id": "PMID:160911", "title": "Myosin-linked calcium regulation in squid mantle muscle. Light-chain components of squid myosin.", "content": "As reported by Kendrick-Jones et al. (1976), myosin from squid mantle muscle contains two types of light-chain components, different in size but similar in net charge. We were able to separate the two types of light chains by a five-step procedure, yielding LC-1 (17,000 daltons) and LC-2 (15,000 daltons). It was found that squid mantle LC-1 and LC-2 function exactly like SH-light chains and EDTA-light chains of scallop adductor myosin, respectively. In functional tests, we used \"desensitized\" myosin of scallop adductor muscle, simply because \"EDTA washing\" removed neither LC-1 nor LC-2 from squid mantle myosin. The removal and recombination of light chains were examined by gel electrophoresis, and Ca or Sr sensitivity was determined by measuring the Mg-ATPase activity of skeletal acto-scallop or squid myosin. It was found that EDTA washing readily released the EDTA-light chains of scallop myosin completely, and that the EDTA-washed scallop myosin was capable of regaining its full content of EDTA-LC as well as its full sensitivity to calcium. We also found that as regards combining with, and conferring calcium sensitivity on the EDTA-washed myosin of scallop adductor, squid mantle LC-2 could effectively replace scallop adductor EDTA-LC. In addition, calcium or strontium ions were found to induce changes in the UV absorption spectrum of scallop adductor EDTA-LC, although the apparent binding constants estimated from the difference spectrum were too low to account for the Ca or Sr sensitivity of scallop actomyosin-ATPase. The divalent cations also induced changes in the UV absorption spectrum of squid LC-2, and the apparent binding constants estimated from the difference spectrum were sufficiently high (1.5 X 10(5) M-1 for Ca binding, and 1.6 X 10(3) M-1 for Sr binding) to account for the Ca and Sr sensitivities of squid mantle myosin B-ATPase. The findings with scallop adductor myosin are in conflict with those reported by Kendrick-Jones et al., and must be accounted for in formulating the molecular mechanism of myosin-linked calcium regulation in molluscan muscles.", "contents": "Myosin-linked calcium regulation in squid mantle muscle. Light-chain components of squid myosin. As reported by Kendrick-Jones et al. (1976), myosin from squid mantle muscle contains two types of light-chain components, different in size but similar in net charge. We were able to separate the two types of light chains by a five-step procedure, yielding LC-1 (17,000 daltons) and LC-2 (15,000 daltons). It was found that squid mantle LC-1 and LC-2 function exactly like SH-light chains and EDTA-light chains of scallop adductor myosin, respectively. In functional tests, we used \"desensitized\" myosin of scallop adductor muscle, simply because \"EDTA washing\" removed neither LC-1 nor LC-2 from squid mantle myosin. The removal and recombination of light chains were examined by gel electrophoresis, and Ca or Sr sensitivity was determined by measuring the Mg-ATPase activity of skeletal acto-scallop or squid myosin. It was found that EDTA washing readily released the EDTA-light chains of scallop myosin completely, and that the EDTA-washed scallop myosin was capable of regaining its full content of EDTA-LC as well as its full sensitivity to calcium. We also found that as regards combining with, and conferring calcium sensitivity on the EDTA-washed myosin of scallop adductor, squid mantle LC-2 could effectively replace scallop adductor EDTA-LC. In addition, calcium or strontium ions were found to induce changes in the UV absorption spectrum of scallop adductor EDTA-LC, although the apparent binding constants estimated from the difference spectrum were too low to account for the Ca or Sr sensitivity of scallop actomyosin-ATPase. The divalent cations also induced changes in the UV absorption spectrum of squid LC-2, and the apparent binding constants estimated from the difference spectrum were sufficiently high (1.5 X 10(5) M-1 for Ca binding, and 1.6 X 10(3) M-1 for Sr binding) to account for the Ca and Sr sensitivities of squid mantle myosin B-ATPase. The findings with scallop adductor myosin are in conflict with those reported by Kendrick-Jones et al., and must be accounted for in formulating the molecular mechanism of myosin-linked calcium regulation in molluscan muscles."} {"id": "PMID:160912", "title": "Nature of adenosine triphosphatase accelerating peptide from hydrolysate of fur seal muscle.", "content": "Ultrafiltered fur seal muscle hydrolysate was divided into eleven fractions by gel filtration on Sephadex G-15. One of the fractions (Fraction G9) accelerated the ATPase activity of carp myosin B to a rate about two-fold faster than that of the control. Fraction G9 showed a single ninhydrin spot in its silica gel thin layer chromatograph, and gave a positive test for tryptophan by the p-dimethylaminobenzaldehyde method, while tests for tyrosine, and for arginine were negative. The ion exchange amino acid analysis of its acid hydrolysate showed a predominant content of lysine, nearly equivalent to the amount of tryptophan determined from its UV absorbancy and the p-dimethylaminobenzaldehyde method. The N-terminal amino acid analysis gave di-DNP-Lys as the sole DNP-amino acid. The structure of the ATPase accelerating peptide fraction, Fraction G9, was deduced to be Lys-Trp.", "contents": "Nature of adenosine triphosphatase accelerating peptide from hydrolysate of fur seal muscle. Ultrafiltered fur seal muscle hydrolysate was divided into eleven fractions by gel filtration on Sephadex G-15. One of the fractions (Fraction G9) accelerated the ATPase activity of carp myosin B to a rate about two-fold faster than that of the control. Fraction G9 showed a single ninhydrin spot in its silica gel thin layer chromatograph, and gave a positive test for tryptophan by the p-dimethylaminobenzaldehyde method, while tests for tyrosine, and for arginine were negative. The ion exchange amino acid analysis of its acid hydrolysate showed a predominant content of lysine, nearly equivalent to the amount of tryptophan determined from its UV absorbancy and the p-dimethylaminobenzaldehyde method. The N-terminal amino acid analysis gave di-DNP-Lys as the sole DNP-amino acid. The structure of the ATPase accelerating peptide fraction, Fraction G9, was deduced to be Lys-Trp."} {"id": "PMID:160913", "title": "Interaction of myosin subfragment-1 with actin. III. Effect of cleavage of the subfragment-1 heavy chain on its interaction with actin.", "content": "To determine the reason why the Mg2+-ATPase activity of subfragment-1 prepared with chymotrypsin was activated more by actin than that of subfragment-1 prepared with trypsin was and the reason why the former could enhance the polymerization of actin and the latter could not, we digested subfragment-1, prepared with chymotrypsin, with trypsin and examined the actin activated Mg2+-ATPase activity and the ability to polymerize actin. It was found that cleavage of the heavy chain decreased the actin activated Mg2+-ATPase activity of subfragment-1 prepared with chymotrypsin but did not affect its ability to polymerize actin. Trypsin attacked the subfragment-1 heavy chain at two sites and produced 26 K, 50 K, and 21 K fragments. From the comparison of the time course of tryptic digestion with that of the decrease in actin activation, it was deduced that cleavage of the 50 K-21 K junction was mainly responsible for the decrease in actin activation. We also measured the length and the amount of F-actin polymerized by the addition of different amounts of subfragment-1. It was found that the amount of F-actin increased with the increase in the amount of subfragment-1 added and that the length of F-actin also increased though slightly. We concluded from the results that subfragment-1 enhanced the polymerization not only by facilitating the nucleus formation but also by strengthening the bond between actin monomers in forming F-actin.", "contents": "Interaction of myosin subfragment-1 with actin. III. Effect of cleavage of the subfragment-1 heavy chain on its interaction with actin. To determine the reason why the Mg2+-ATPase activity of subfragment-1 prepared with chymotrypsin was activated more by actin than that of subfragment-1 prepared with trypsin was and the reason why the former could enhance the polymerization of actin and the latter could not, we digested subfragment-1, prepared with chymotrypsin, with trypsin and examined the actin activated Mg2+-ATPase activity and the ability to polymerize actin. It was found that cleavage of the heavy chain decreased the actin activated Mg2+-ATPase activity of subfragment-1 prepared with chymotrypsin but did not affect its ability to polymerize actin. Trypsin attacked the subfragment-1 heavy chain at two sites and produced 26 K, 50 K, and 21 K fragments. From the comparison of the time course of tryptic digestion with that of the decrease in actin activation, it was deduced that cleavage of the 50 K-21 K junction was mainly responsible for the decrease in actin activation. We also measured the length and the amount of F-actin polymerized by the addition of different amounts of subfragment-1. It was found that the amount of F-actin increased with the increase in the amount of subfragment-1 added and that the length of F-actin also increased though slightly. We concluded from the results that subfragment-1 enhanced the polymerization not only by facilitating the nucleus formation but also by strengthening the bond between actin monomers in forming F-actin."} {"id": "PMID:160914", "title": "Induction of enzyme-altered islands in rat liver by tryptophan pyrolysis products.", "content": "Two new gamma-carboline derivatives, 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H pyrido[4,3-b]indole (Trp-P-2), isolated from the pyrolysis products of tryptophan, were found to be potent mutagens. When weanling rats were injected with Trp-P-1 and then given diet containing phenobarbital, they developed enzyme-altered islands in the liver. Since these islands are considered to be formed by immediate progeny of \"initiated cells\" and cell precursors in hepatocarcinogenesis, Trp-P-1 may well be carcinogenic in rat liver.", "contents": "Induction of enzyme-altered islands in rat liver by tryptophan pyrolysis products. Two new gamma-carboline derivatives, 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H pyrido[4,3-b]indole (Trp-P-2), isolated from the pyrolysis products of tryptophan, were found to be potent mutagens. When weanling rats were injected with Trp-P-1 and then given diet containing phenobarbital, they developed enzyme-altered islands in the liver. Since these islands are considered to be formed by immediate progeny of \"initiated cells\" and cell precursors in hepatocarcinogenesis, Trp-P-1 may well be carcinogenic in rat liver."} {"id": "PMID:160915", "title": "Activities of four glycolytic enzymes (HK, PFK, PK, and LDH) and isozymic pattern of LDH in mouse lung tumor induced by urethan.", "content": "In the lungs of CFLP mice the activities of glycolytic key enzymes (HK, PFK, PK) and LDH as well as LDH isozymic pattern change in the course of life. The activities of these glycolytic enzymes in the lung tumors induced by urethan in CFLP mice are significantly higher than those in the normal adult lung and they are similar to those in the normal fetal lung. The isozymic pattern of LDH of pulmonary adenomas resembles that of the normal fetal lung, too.", "contents": "Activities of four glycolytic enzymes (HK, PFK, PK, and LDH) and isozymic pattern of LDH in mouse lung tumor induced by urethan. In the lungs of CFLP mice the activities of glycolytic key enzymes (HK, PFK, PK) and LDH as well as LDH isozymic pattern change in the course of life. The activities of these glycolytic enzymes in the lung tumors induced by urethan in CFLP mice are significantly higher than those in the normal adult lung and they are similar to those in the normal fetal lung. The isozymic pattern of LDH of pulmonary adenomas resembles that of the normal fetal lung, too."} {"id": "PMID:160916", "title": "An improved and easy technique for polyamine determination in biological samples. Application to cell-free system from hypertrophied rat heart.", "content": "An accurate, improved cation-exchange chromatographic method using o-phthalaldehyde and ultraviolet detection at 280 nm for the determination of free polyamines (putrescine, spermidine, spermine) has been developed. Different samples, such as the 105,000 g supernatant of reticulocyte or heart muscle, and KCl ribosomal wash containing initiation factors, can be analysed. The minor modification of reagents results in a good precision and sensitivity, which is demonstrated by a relative standard deviation of 5--9% and recoveries of 98%. This technique is of particular interest because it allows polyamine determination in biological samples with high concentrations of salt.", "contents": "An improved and easy technique for polyamine determination in biological samples. Application to cell-free system from hypertrophied rat heart. An accurate, improved cation-exchange chromatographic method using o-phthalaldehyde and ultraviolet detection at 280 nm for the determination of free polyamines (putrescine, spermidine, spermine) has been developed. Different samples, such as the 105,000 g supernatant of reticulocyte or heart muscle, and KCl ribosomal wash containing initiation factors, can be analysed. The minor modification of reagents results in a good precision and sensitivity, which is demonstrated by a relative standard deviation of 5--9% and recoveries of 98%. This technique is of particular interest because it allows polyamine determination in biological samples with high concentrations of salt."} {"id": "PMID:160918", "title": "Colonization and infection of newborn infants caused by bacteriophage-group II Staphylococcus aureus strains.", "content": "A staphylococcal strain which exhibited weak lytic reaction with group II phages was isolated from a newborn infant with a skin infection. Subsequent investigations established that this weakly reacting strain was responsible for an endemic level of infection and colonization within the hospital nursery. The use of consistently appearing weak lytic reactions in the evaluation of this episode is described.", "contents": "Colonization and infection of newborn infants caused by bacteriophage-group II Staphylococcus aureus strains. A staphylococcal strain which exhibited weak lytic reaction with group II phages was isolated from a newborn infant with a skin infection. Subsequent investigations established that this weakly reacting strain was responsible for an endemic level of infection and colonization within the hospital nursery. The use of consistently appearing weak lytic reactions in the evaluation of this episode is described."} {"id": "PMID:160919", "title": "The edema of fiddler's neck.", "content": "Fiddler's neck is a dermatosis of violinists and violists. It characteristically presents as focal lichenification and pigmentation on the left side of the neck. Edema may also occur in the same area and lead to cosmetic concern or fear of malignancy. The edema apparently results from pressure on the patient's neck by the base of the violin or viola and is worsened by holding the instrument in a drooping position.", "contents": "The edema of fiddler's neck. Fiddler's neck is a dermatosis of violinists and violists. It characteristically presents as focal lichenification and pigmentation on the left side of the neck. Edema may also occur in the same area and lead to cosmetic concern or fear of malignancy. The edema apparently results from pressure on the patient's neck by the base of the violin or viola and is worsened by holding the instrument in a drooping position."} {"id": "PMID:160920", "title": "Effect of experimental magnetic storm on the production of lambda phage.", "content": "1. Sharp fluctuation of the intensity of the vertical component of the MF amounting to +/- 0.1 Oe changing the sign over each 3 min causes variability of both lysogenic and indicator strains of E. coli. This testifies to an extremely low threshold of their magnetic susceptibility and to biological importance of fluctuations of natural parameters of the geomagnetic field as an ecological factor of the environment. 2. A change in the intensity of the vertical component of the MF, not any higher than +/-0.1 Oe, inhibits phage production in the lysogenic system of E. coli K = 12 lambda and is also reflected in the morphological peculiarities of negative phage colonies as well as in the phage-susceptibility of the E. coli indicator strain.", "contents": "Effect of experimental magnetic storm on the production of lambda phage. 1. Sharp fluctuation of the intensity of the vertical component of the MF amounting to +/- 0.1 Oe changing the sign over each 3 min causes variability of both lysogenic and indicator strains of E. coli. This testifies to an extremely low threshold of their magnetic susceptibility and to biological importance of fluctuations of natural parameters of the geomagnetic field as an ecological factor of the environment. 2. A change in the intensity of the vertical component of the MF, not any higher than +/-0.1 Oe, inhibits phage production in the lysogenic system of E. coli K = 12 lambda and is also reflected in the morphological peculiarities of negative phage colonies as well as in the phage-susceptibility of the E. coli indicator strain."} {"id": "PMID:160924", "title": "Avoidance of the handicapped: an attributional ambiguity analysis.", "content": "We demonstrated a general strategy for detecting motives that people wish to conceal. The strategy consists of having people choose between two alternatives, one of which happens to satisfy the motive. By counterbalancing which one does so, it is possible to distill the motive by examining the pattern of choices that people make. The motive used in the demonstration is the desire we believe most people have to avoid the physically handicapped. Because they do not wish to reveal this desire, we predicted that they would be more likely to act on it if they could appear to choose on some other basis. In two studies we found that people avoided the handicapped more often if the decision to do so was also a decision between two movies and avoidance of the handicapped could masquerade as a movie preference.", "contents": "Avoidance of the handicapped: an attributional ambiguity analysis. We demonstrated a general strategy for detecting motives that people wish to conceal. The strategy consists of having people choose between two alternatives, one of which happens to satisfy the motive. By counterbalancing which one does so, it is possible to distill the motive by examining the pattern of choices that people make. The motive used in the demonstration is the desire we believe most people have to avoid the physically handicapped. Because they do not wish to reveal this desire, we predicted that they would be more likely to act on it if they could appear to choose on some other basis. In two studies we found that people avoided the handicapped more often if the decision to do so was also a decision between two movies and avoidance of the handicapped could masquerade as a movie preference."} {"id": "PMID:160923", "title": "L-Thyroxine effects upon ATPase activities of several subcellular fractions of liver of the rat and the guinea pig.", "content": "The effect of thyroxine administration upon ATPase activity of several subcellular fractions of livers from rats and guinea pigs has been studied. To determine a patho-physiological dose of levo thyroxine [T4] for guinea pigs, a dose-response curve was examined of T4 effect upon oxidative phosphorylatin of guinea pig liver mitochondria. Maximum stimulation of mitochondrial respiration without uncoupling of oxidative phosphorylation was found with 15 microgram of T4 per 100 g body weight per day. This dose of T4 stimulated Mg++ activated ATPase of plasma membranes of guinea pigs and slightly stimulated Mg++ activated ATPase of guinea pig liver nuclear membranes. Rat liver nuclear membrane ATPase was not responsive to thyroxine at doses from 5 to 150 microgram per 100 g body weight. T4 significantly stimulated Ca++ or Mg++ ATPase of mitochondria and microsomes from both rat and guinea pig liver. Microsomes from both species were maximally activated by Mg++ and no significant additional stimulation with Ca++ was found. Mitochondrial ATPase from both species showed significantly greater Ca++ plus Mg++ ATPase activity than did Mg++ alone. Ca++ activated ATPase was approximately equal to dinitrophenol stimulated mitochondrial ATPase. Maximum activation of microsomal ATPase in both species was found with 1 mM calcium. We conclude that at physiological-intracellular concentrations of Ca++ and Mg++, thyroxine probably stimulates Mg++ activated microsomal ATPase and Ca++ activated mitochondrial ATPase. A potential role of Ca++ as a moderator of thyroxine stimulated activity in mitochondria and the relation of calcium to other metabolic reactions that are thyroxine sensitive is discussed.", "contents": "L-Thyroxine effects upon ATPase activities of several subcellular fractions of liver of the rat and the guinea pig. The effect of thyroxine administration upon ATPase activity of several subcellular fractions of livers from rats and guinea pigs has been studied. To determine a patho-physiological dose of levo thyroxine [T4] for guinea pigs, a dose-response curve was examined of T4 effect upon oxidative phosphorylatin of guinea pig liver mitochondria. Maximum stimulation of mitochondrial respiration without uncoupling of oxidative phosphorylation was found with 15 microgram of T4 per 100 g body weight per day. This dose of T4 stimulated Mg++ activated ATPase of plasma membranes of guinea pigs and slightly stimulated Mg++ activated ATPase of guinea pig liver nuclear membranes. Rat liver nuclear membrane ATPase was not responsive to thyroxine at doses from 5 to 150 microgram per 100 g body weight. T4 significantly stimulated Ca++ or Mg++ ATPase of mitochondria and microsomes from both rat and guinea pig liver. Microsomes from both species were maximally activated by Mg++ and no significant additional stimulation with Ca++ was found. Mitochondrial ATPase from both species showed significantly greater Ca++ plus Mg++ ATPase activity than did Mg++ alone. Ca++ activated ATPase was approximately equal to dinitrophenol stimulated mitochondrial ATPase. Maximum activation of microsomal ATPase in both species was found with 1 mM calcium. We conclude that at physiological-intracellular concentrations of Ca++ and Mg++, thyroxine probably stimulates Mg++ activated microsomal ATPase and Ca++ activated mitochondrial ATPase. A potential role of Ca++ as a moderator of thyroxine stimulated activity in mitochondria and the relation of calcium to other metabolic reactions that are thyroxine sensitive is discussed."} {"id": "PMID:160929", "title": "Changes in rodent muscle fibre types during post-natal growth, undernutrition and exercise.", "content": "1. Using histochemical staining methods for myosin ATPase oxidative and glycolytic enzymes, three major types of muscle fibre could be identified in the skeletal muscle of hamsters and mice. 2. Muscle fibre counts showed that the proportions of the different fibres were not entirely stable with age. In the hamster biceps brachii which is predominantly composed of ATPase-high fibres there was a decrease in the number of ATPase-low fibres. In the soleus muscle which is predominantly composed of ATPase-low fibres there was a decrease in ATPase-high fibres with age. 3. Although there was a change in the proportions of fibre types there was no change in the total number of fibres within the muscles with age. It is suggested that some reinnervation may take place during growth and that this is why the less dedominant fibre type decreases. 4. The response of the different fibre types to partial starvation was studied. The ATPase-high fibres showed the greatest decrease in size. Of these, the ATPase-high glycolytic type responded more than the ATPase-high oxidative type. The effects of the under-nutrition on the different fibre types were found to be completely reversible. Starvation did not affect the total number of fibres or the numbers of any fibre type. 5. The response of the different types to high intensity exercise (weight lifting) was studied. This type of exercise resulted in hypertrophy of all three major fibre types. However, the extent of the response varied according to the fibre type and the exact nature of the exercise. In most cases the ATPase-high fibres underwent hypertrophy more readily than the ATPase-low fibres. Where distinction was made between the two types of ATPase-high fibres, the ATPase-high glycolytic were found to hypertrophy more than the ATPase-high oxidative fibres. The effects of post exercise recovery (return to relative inactivity) were also studied and the changes in size of the fibres were found to be completely reversible.", "contents": "Changes in rodent muscle fibre types during post-natal growth, undernutrition and exercise. 1. Using histochemical staining methods for myosin ATPase oxidative and glycolytic enzymes, three major types of muscle fibre could be identified in the skeletal muscle of hamsters and mice. 2. Muscle fibre counts showed that the proportions of the different fibres were not entirely stable with age. In the hamster biceps brachii which is predominantly composed of ATPase-high fibres there was a decrease in the number of ATPase-low fibres. In the soleus muscle which is predominantly composed of ATPase-low fibres there was a decrease in ATPase-high fibres with age. 3. Although there was a change in the proportions of fibre types there was no change in the total number of fibres within the muscles with age. It is suggested that some reinnervation may take place during growth and that this is why the less dedominant fibre type decreases. 4. The response of the different fibre types to partial starvation was studied. The ATPase-high fibres showed the greatest decrease in size. Of these, the ATPase-high glycolytic type responded more than the ATPase-high oxidative type. The effects of the under-nutrition on the different fibre types were found to be completely reversible. Starvation did not affect the total number of fibres or the numbers of any fibre type. 5. The response of the different types to high intensity exercise (weight lifting) was studied. This type of exercise resulted in hypertrophy of all three major fibre types. However, the extent of the response varied according to the fibre type and the exact nature of the exercise. In most cases the ATPase-high fibres underwent hypertrophy more readily than the ATPase-low fibres. Where distinction was made between the two types of ATPase-high fibres, the ATPase-high glycolytic were found to hypertrophy more than the ATPase-high oxidative fibres. The effects of post exercise recovery (return to relative inactivity) were also studied and the changes in size of the fibres were found to be completely reversible."} {"id": "PMID:160938", "title": "[Mediastinal bronchogenic cysts in adults. Cardiovascular symptomatology (author's transl)].", "content": "The authors describe seven patients operated upon for mediastinal bronchogenic cysts and emphasize the problems of differential diagnosis from cardiac and vascular affections: enlarged left auricle and aneurysm of the thoracic aorta. They review the published literature on atypical bronchogenic cysts with cardiac or vascular symptoms, and the diagnostic problems they raise in adults.", "contents": "[Mediastinal bronchogenic cysts in adults. Cardiovascular symptomatology (author's transl)]. The authors describe seven patients operated upon for mediastinal bronchogenic cysts and emphasize the problems of differential diagnosis from cardiac and vascular affections: enlarged left auricle and aneurysm of the thoracic aorta. They review the published literature on atypical bronchogenic cysts with cardiac or vascular symptoms, and the diagnostic problems they raise in adults."} {"id": "PMID:160956", "title": "[Clinical experience of cefoxitin in the field of obstetrics and gynecology (author's transl)].", "content": "Cefoxitin was given to the 7 patients of infections in the field of obstetrics and gynecology, and the following results were obtained: 1) The clinical response was excellent in 2 patients, good in 4 and poor in 1 patient with the efficacy rate of 85.7%. Out of the 4 patients resistant to the previous therapy with other antibiotics, 3 patients responded to cefoxitin, and all the 3 patients of anaerobic infections responded satisfactorily to cefoxitin. 2) Microorganisms isolated were 2 strains each of E. coli and Staphylococcus aureus, 3 strains of Peptococcus and 1 strain of Eubacterium lentum. All the 8 strains isolated were sensitive to cefoxitin. As to bacteriological response, all the strains isolated were eradicated except 1 strain of Staphylococcus aureus which recurred on the 9th day after completion of the therapy with the eradication rate of 87.5%. 3) No subjective nor objective side effects were noted. Especially, the elevated GOT and GPT observed on a patient complicated with hepatitis prior to the initiation of cefoxitin treatment were found to be normal upon completion of the treatment.", "contents": "[Clinical experience of cefoxitin in the field of obstetrics and gynecology (author's transl)]. Cefoxitin was given to the 7 patients of infections in the field of obstetrics and gynecology, and the following results were obtained: 1) The clinical response was excellent in 2 patients, good in 4 and poor in 1 patient with the efficacy rate of 85.7%. Out of the 4 patients resistant to the previous therapy with other antibiotics, 3 patients responded to cefoxitin, and all the 3 patients of anaerobic infections responded satisfactorily to cefoxitin. 2) Microorganisms isolated were 2 strains each of E. coli and Staphylococcus aureus, 3 strains of Peptococcus and 1 strain of Eubacterium lentum. All the 8 strains isolated were sensitive to cefoxitin. As to bacteriological response, all the strains isolated were eradicated except 1 strain of Staphylococcus aureus which recurred on the 9th day after completion of the therapy with the eradication rate of 87.5%. 3) No subjective nor objective side effects were noted. Especially, the elevated GOT and GPT observed on a patient complicated with hepatitis prior to the initiation of cefoxitin treatment were found to be normal upon completion of the treatment."} {"id": "PMID:160963", "title": "Immunologic aspects of renal lesions associated with malaria.", "content": "Studies on experimental models of infections and observations in man indicate that immune complexes (IC) play an important role in the pathogenesis of nephropathies associated with malaria. All present evidence suggests that IC preformed in circulation localize in the glomeruli and initiate the lesions. In acute lesions, typical of falciparum infections in man, the depositions of IC are found quite soon after infection; glomerular injury is reversible, and these cases respond well to antimalarial therapy. Chronic lesions, typical for quartan malaria, are more progressive and do not respond to antimalarials. Deposits of IC in glomeruli have shown the presence of malarial antigens at the beginning, but the perpetuation of the lesions does not seem to be due to constant supply of malarial antigens. The possibility that malarial IC in these chronic lesions trigger a pathogenic sequence in which other mechanisms (perhaps autoimmune?) are later involved is discussed.", "contents": "Immunologic aspects of renal lesions associated with malaria. Studies on experimental models of infections and observations in man indicate that immune complexes (IC) play an important role in the pathogenesis of nephropathies associated with malaria. All present evidence suggests that IC preformed in circulation localize in the glomeruli and initiate the lesions. In acute lesions, typical of falciparum infections in man, the depositions of IC are found quite soon after infection; glomerular injury is reversible, and these cases respond well to antimalarial therapy. Chronic lesions, typical for quartan malaria, are more progressive and do not respond to antimalarials. Deposits of IC in glomeruli have shown the presence of malarial antigens at the beginning, but the perpetuation of the lesions does not seem to be due to constant supply of malarial antigens. The possibility that malarial IC in these chronic lesions trigger a pathogenic sequence in which other mechanisms (perhaps autoimmune?) are later involved is discussed."} {"id": "PMID:160972", "title": "Influence of SOS repair on the specificity of radiation mutagenesis in bacteriophage phiX174.", "content": "The ochre mutant oc9 of bacteriophage phiX174 was irradiated with gamma-rays and the revertants were assayed on unirradiated and UV-irradiated host bacteria carrying an amber suppressor. The yield of revertants (amber + wild type) was higher on UV-irradiated than on unirradiated bacteria, showing that gamma-irradiated phiX174 was subjected to W-mutagenesis. For oc9 gamma-irradiated in the presence of oxygen the fraction of amber mutants among the revertants was lower when mutants were scored on UV-irradiated bacteria than when assayed on unirradiated indicator cells. The same fraction of ambers was obtained when mutants were assayed on unirradiated and UV-irradiated samples of a recA indicator strain. UV-irradiated phiX174 showed a similar phenomenon. These results suggest that the specificity with regard to insertion of bases opposite radiation damage in phiX174 DNA is different for host cells in which SOS repair has been induced and cells in which SOS repair is not operative.", "contents": "Influence of SOS repair on the specificity of radiation mutagenesis in bacteriophage phiX174. The ochre mutant oc9 of bacteriophage phiX174 was irradiated with gamma-rays and the revertants were assayed on unirradiated and UV-irradiated host bacteria carrying an amber suppressor. The yield of revertants (amber + wild type) was higher on UV-irradiated than on unirradiated bacteria, showing that gamma-irradiated phiX174 was subjected to W-mutagenesis. For oc9 gamma-irradiated in the presence of oxygen the fraction of amber mutants among the revertants was lower when mutants were scored on UV-irradiated bacteria than when assayed on unirradiated indicator cells. The same fraction of ambers was obtained when mutants were assayed on unirradiated and UV-irradiated samples of a recA indicator strain. UV-irradiated phiX174 showed a similar phenomenon. These results suggest that the specificity with regard to insertion of bases opposite radiation damage in phiX174 DNA is different for host cells in which SOS repair has been induced and cells in which SOS repair is not operative."} {"id": "PMID:160973", "title": "Mini-muduction: a new mode of gene transfer mediated by mini-mu.", "content": "We compared the transducing properties of Mucts62 and Mucts62/mini-Mu lysates, using Mu immune and non immune Recqnd recA recipient strains. The Mu/mini-Mu lysates transduced all bacterial markers tested 10 times more efficiently than the Mucts62 lysates in Rec + recipients. Most of the transductants obtained after infection with the Mu/mini-Mu lysates result from the substitution of the mutated gene of the recipient by the wild type allele from the donor, most probably carried on the gigantic variable end linked to the mini-Mu genome. Moreover the Mu/mini-Mu lysates gave a new type of Rec-independent transduction that we called mini-muduction. Mini-muduction requires the activity of Mu gene A and provides transductants which carry the transduced marker surrounded by two mini-Mu genomes similarly oriented, and inserted at random location in the recipient chromosome. The mini-Mu/transduced DNA/mini-Mu structures are able to transpose spontaneously, for instance into a transmissible plasmid, in the presence of Mu gene A product.", "contents": "Mini-muduction: a new mode of gene transfer mediated by mini-mu. We compared the transducing properties of Mucts62 and Mucts62/mini-Mu lysates, using Mu immune and non immune Recqnd recA recipient strains. The Mu/mini-Mu lysates transduced all bacterial markers tested 10 times more efficiently than the Mucts62 lysates in Rec + recipients. Most of the transductants obtained after infection with the Mu/mini-Mu lysates result from the substitution of the mutated gene of the recipient by the wild type allele from the donor, most probably carried on the gigantic variable end linked to the mini-Mu genome. Moreover the Mu/mini-Mu lysates gave a new type of Rec-independent transduction that we called mini-muduction. Mini-muduction requires the activity of Mu gene A and provides transductants which carry the transduced marker surrounded by two mini-Mu genomes similarly oriented, and inserted at random location in the recipient chromosome. The mini-Mu/transduced DNA/mini-Mu structures are able to transpose spontaneously, for instance into a transmissible plasmid, in the presence of Mu gene A product."} {"id": "PMID:160970", "title": "[Distribution of dracunculiasis in Mali. A survey of the Cyclops habitat (author's transl)].", "content": "The authors report the distribution and the incidence of dracunculiasis in the seven administrative regions of Mali. They describe the various types of Cyclops habitat and the seasonal variations in transmission. They discuss the resulting effects of dryness and rural water development on this endemic parasitic disease.", "contents": "[Distribution of dracunculiasis in Mali. A survey of the Cyclops habitat (author's transl)]. The authors report the distribution and the incidence of dracunculiasis in the seven administrative regions of Mali. They describe the various types of Cyclops habitat and the seasonal variations in transmission. They discuss the resulting effects of dryness and rural water development on this endemic parasitic disease."} {"id": "PMID:160974", "title": "Genetics of oxidative phosphorylation: mitochondrial loci determining ossamycin-, venturicidin- and oligomycin-resistance in yeast.", "content": "With a view towards identifying new ATPase loci on the mitochondrial genome a large number of oligomycin-, ossamycin- and venturicidin-resistant mutants were isolated after MnCl2 mutagenesis. The mutants were subjected to mass-screens which divided them into different cross-resistance phenotype-classes and also distinguished the common OLI1 mutations from the mutations at all other loci. Allelism tests between examples of the different classes of phenotype indicated that the majority of mutations in the population mapped at the previously known loci OLI1, OLI2, OLI3, and OLI4. Mutations conferring specific ossamycin resistance defined two new loci, namely OSS1 and OSS2 which are linked to the OLI2 and OLI1 loci respectively. A few rare mutations comprise a new locus OLI5 which is linked to the OLI1 locus (12.6% total recombination). In conclusion we can now say that that there are two unlinked segments of the mitochondrial genome, each of which is composed of several distinct, genetically-linked loci. One segment contains the OLI1, OLI3, OLI5 and OSS2 loci and the other the OLI2, OLI4 and OSS1 loci. The phenotypically-distinguishable mutations described herein should facilitate fine-structure mapping of these two segments.", "contents": "Genetics of oxidative phosphorylation: mitochondrial loci determining ossamycin-, venturicidin- and oligomycin-resistance in yeast. With a view towards identifying new ATPase loci on the mitochondrial genome a large number of oligomycin-, ossamycin- and venturicidin-resistant mutants were isolated after MnCl2 mutagenesis. The mutants were subjected to mass-screens which divided them into different cross-resistance phenotype-classes and also distinguished the common OLI1 mutations from the mutations at all other loci. Allelism tests between examples of the different classes of phenotype indicated that the majority of mutations in the population mapped at the previously known loci OLI1, OLI2, OLI3, and OLI4. Mutations conferring specific ossamycin resistance defined two new loci, namely OSS1 and OSS2 which are linked to the OLI2 and OLI1 loci respectively. A few rare mutations comprise a new locus OLI5 which is linked to the OLI1 locus (12.6% total recombination). In conclusion we can now say that that there are two unlinked segments of the mitochondrial genome, each of which is composed of several distinct, genetically-linked loci. One segment contains the OLI1, OLI3, OLI5 and OSS2 loci and the other the OLI2, OLI4 and OSS1 loci. The phenotypically-distinguishable mutations described herein should facilitate fine-structure mapping of these two segments."} {"id": "PMID:160975", "title": "The origin of the DNA in transducing particles of bacteriophage Mu. Density gradient analyses of intact phages.", "content": "The origin of DNA in transducing particles of bacteriophage Mu was investigated by density labelling techniques. Unlabelled plaque-forming and leu+-transducing particles were of about the same density. Preinfection labelling of DNA with 5-bromodeoxyuridine increased the density of the transducing particles, but not that of the infective ones. Postinfection labelling increased the density of the infective particles twice as much as that of the transducing particles. We conclude that half of the transducing DNA is synthesized before infection and half is synthesized after infection, similar to the results obtained with P1kc transducing phages (Ikeda and Tomizawa, 1965).", "contents": "The origin of the DNA in transducing particles of bacteriophage Mu. Density gradient analyses of intact phages. The origin of DNA in transducing particles of bacteriophage Mu was investigated by density labelling techniques. Unlabelled plaque-forming and leu+-transducing particles were of about the same density. Preinfection labelling of DNA with 5-bromodeoxyuridine increased the density of the transducing particles, but not that of the infective ones. Postinfection labelling increased the density of the infective particles twice as much as that of the transducing particles. We conclude that half of the transducing DNA is synthesized before infection and half is synthesized after infection, similar to the results obtained with P1kc transducing phages (Ikeda and Tomizawa, 1965)."} {"id": "PMID:160979", "title": "Mixed-lymphocyte culture response in a related and an unrelated Australian population.", "content": "In 256 related combinations in an Australian Caucasian population, the relative responses in one-way mixed-lymphocyte cultures can be divided into four different groups: (i) HLA zero-haplotype different; (ii) HLA-D homozygous-versus-heterozygous; (iii) HLA one-haplotype different: and (iv) HLA two-haplotype different. The median relative responses of the groups were 0.78%, 20%, 64% and 86.5%, respectively; 17.7% of HLA-A, HLA-B identical siblings were found to stimulate significantly in mixed-lymphocyte culture, and 6.3% of HLA one-haplotype different combinations had weak responses. The median relative response of 225 unrelated random combinations was 100%. One mixed-lymphocyte culture combination in this group gave a relative response of 20%, which was found to be a HLA-D homozygous-versus-heterozygous response. A relative response of 20% in mixed-lymphocyte cultures may be taken to indicate relative HLA-D compatibility and would, therefore, predict a favourable outcome in kidney transplantation. The use of mixed-lymphocyte cultures as a routine in selecting suitable donors in living related transplants and, retrospectively, in monitoring the results of cadaveric transplants, is advocated.", "contents": "Mixed-lymphocyte culture response in a related and an unrelated Australian population. In 256 related combinations in an Australian Caucasian population, the relative responses in one-way mixed-lymphocyte cultures can be divided into four different groups: (i) HLA zero-haplotype different; (ii) HLA-D homozygous-versus-heterozygous; (iii) HLA one-haplotype different: and (iv) HLA two-haplotype different. The median relative responses of the groups were 0.78%, 20%, 64% and 86.5%, respectively; 17.7% of HLA-A, HLA-B identical siblings were found to stimulate significantly in mixed-lymphocyte culture, and 6.3% of HLA one-haplotype different combinations had weak responses. The median relative response of 225 unrelated random combinations was 100%. One mixed-lymphocyte culture combination in this group gave a relative response of 20%, which was found to be a HLA-D homozygous-versus-heterozygous response. A relative response of 20% in mixed-lymphocyte cultures may be taken to indicate relative HLA-D compatibility and would, therefore, predict a favourable outcome in kidney transplantation. The use of mixed-lymphocyte cultures as a routine in selecting suitable donors in living related transplants and, retrospectively, in monitoring the results of cadaveric transplants, is advocated."} {"id": "PMID:160983", "title": "Some peculiarities of osteomedullary interrelations at the level of the lateral wall of the maxillary sinus.", "content": "Several structural aspects in the lateral wall of the maxillary sinus are shown, revealing the existence of some peculiarities of the osteomedullary relationships at this level, as for instance: a) a great density of vascular canals, b) a marked collagen density and a high degree of polymerization of the ground substance pleading for a great stability of the osseous structure, and c) a relative cellular scarcity inside the marrow-like spaces as an expression of a reduced reactive ability of bone marrow. It is considered that these peculiarities are not merely determined by specific functional needs of the bone as a tissue, but mainly by subordination of the latter to the requirements of the higher-ordered structural and functional levels served by a certain osseous zone.", "contents": "Some peculiarities of osteomedullary interrelations at the level of the lateral wall of the maxillary sinus. Several structural aspects in the lateral wall of the maxillary sinus are shown, revealing the existence of some peculiarities of the osteomedullary relationships at this level, as for instance: a) a great density of vascular canals, b) a marked collagen density and a high degree of polymerization of the ground substance pleading for a great stability of the osseous structure, and c) a relative cellular scarcity inside the marrow-like spaces as an expression of a reduced reactive ability of bone marrow. It is considered that these peculiarities are not merely determined by specific functional needs of the bone as a tissue, but mainly by subordination of the latter to the requirements of the higher-ordered structural and functional levels served by a certain osseous zone."} {"id": "PMID:160985", "title": "[Dynamics of the action of cyclophosphamide. Studies in the chick embryo].", "content": "The dynamics of the Cyclophosphamide (CPA) effect was investigated in the chick embryo by a vital fluorochroming method worked out previously. In the 4-day-old embryo the morphological changes (at the level of light microscopy) in the limbs and in the mesencephalon induced by 100 microgram CPA appeared after a period of latency of about 10 hours. Successive blood control in the same embryo, treated with 50 microgram CPA, revealed three consecutive modifications of the blood cells: a great number of abnormal mitoses, the appearance of a great number of multinucleated, nonviable cells and the recovery of the lost cells. No difference could be detected between the effect of freshly prepared and stored CPA solutions. The fate of CPA (a bifunctionally alkylating agent) in contact with living tissues is discussed.", "contents": "[Dynamics of the action of cyclophosphamide. Studies in the chick embryo]. The dynamics of the Cyclophosphamide (CPA) effect was investigated in the chick embryo by a vital fluorochroming method worked out previously. In the 4-day-old embryo the morphological changes (at the level of light microscopy) in the limbs and in the mesencephalon induced by 100 microgram CPA appeared after a period of latency of about 10 hours. Successive blood control in the same embryo, treated with 50 microgram CPA, revealed three consecutive modifications of the blood cells: a great number of abnormal mitoses, the appearance of a great number of multinucleated, nonviable cells and the recovery of the lost cells. No difference could be detected between the effect of freshly prepared and stored CPA solutions. The fate of CPA (a bifunctionally alkylating agent) in contact with living tissues is discussed."} {"id": "PMID:160986", "title": "The concept of chronic pathological processes.", "content": "The chronic pattern of lesions and the behaviour of each process as a whole, the internal relationships between sequences, the dynamics of factor assemblies determining the sequences and development of lesional chains, the propelling and cohesional factors are analysed in the morphopathogenic modalities of chronic processes, the chronic transformation of acute lesions and the primary chronic processes. This structural analysis lends support to the consideration of chronic pathological processes as systems and their investigation by the methods of the systemic conception applied to pathology. Key words: chronic pathological processes, chronic pattern of lesions, chronic transformation of acute lesions, primary chronic processes, sequential development, assemblies of factors, propelling factors, cohensional factors, proliferative dominance, self-perpetuation and auto-aggression mechanisms, stereotyping of chronic processes, systemic conception.", "contents": "The concept of chronic pathological processes. The chronic pattern of lesions and the behaviour of each process as a whole, the internal relationships between sequences, the dynamics of factor assemblies determining the sequences and development of lesional chains, the propelling and cohesional factors are analysed in the morphopathogenic modalities of chronic processes, the chronic transformation of acute lesions and the primary chronic processes. This structural analysis lends support to the consideration of chronic pathological processes as systems and their investigation by the methods of the systemic conception applied to pathology. Key words: chronic pathological processes, chronic pattern of lesions, chronic transformation of acute lesions, primary chronic processes, sequential development, assemblies of factors, propelling factors, cohensional factors, proliferative dominance, self-perpetuation and auto-aggression mechanisms, stereotyping of chronic processes, systemic conception."} {"id": "PMID:160984", "title": "The Kupffer cells. Ultrastructural and functional features.", "content": "The Kupffer cells, as fixed macrophages, belong to the mononuclear phagocyte system (MPS), the former reticulo-endothelial system (RES). Their ultrastructure has some characteristics, i.e. ergastroplasmic peroxidase activity and worm-like structures, which allow a very sharp identification. Some particular \"bridge-like\" arrangements of Kupffer cells in the capillary lumen seem to provide them with a special ability of \"trapping\" the passing white blood cells. The important endocytotic function is analysed from the viewpoint of ultrastructural features, and with particular reference to the phagocytosis of damaged red blood cells. Several drugs and particulate substances acting as Kupffer cells stimulants are presented. This stimulation reaction concerns woth increased number and enhanced endocytotic activity. The origin and kinetics of Kupffer cells are discussed, with reference to own results which substantiate the theory of local proliferation and blood supply, the bone marrow being however the main source of hepatic macrophages. A few ultrastructural data on Kupffer cells involved in pathological processes are presented.", "contents": "The Kupffer cells. Ultrastructural and functional features. The Kupffer cells, as fixed macrophages, belong to the mononuclear phagocyte system (MPS), the former reticulo-endothelial system (RES). Their ultrastructure has some characteristics, i.e. ergastroplasmic peroxidase activity and worm-like structures, which allow a very sharp identification. Some particular \"bridge-like\" arrangements of Kupffer cells in the capillary lumen seem to provide them with a special ability of \"trapping\" the passing white blood cells. The important endocytotic function is analysed from the viewpoint of ultrastructural features, and with particular reference to the phagocytosis of damaged red blood cells. Several drugs and particulate substances acting as Kupffer cells stimulants are presented. This stimulation reaction concerns woth increased number and enhanced endocytotic activity. The origin and kinetics of Kupffer cells are discussed, with reference to own results which substantiate the theory of local proliferation and blood supply, the bone marrow being however the main source of hepatic macrophages. A few ultrastructural data on Kupffer cells involved in pathological processes are presented."} {"id": "PMID:160987", "title": "On the mechanisms of ischaemic myocardial lesions.", "content": "The examination of the myocardium in 609 natural and violent death cases by using Lie's histochemical method revealed recent ischaemic lesions, extended or microfocal, in 511 cases. These lesions were prevailingly extended in sudden cardiac deaths, alcoholic intoxication and electrocution, while in the various kinds of shock, in asphyxia and pesticide poisoning cases they were of a predominantly microfocal nature. According to these morphological changes, the vascular and metabolic factors involved in producing ischaemic cardiomyopathy are discussed.", "contents": "On the mechanisms of ischaemic myocardial lesions. The examination of the myocardium in 609 natural and violent death cases by using Lie's histochemical method revealed recent ischaemic lesions, extended or microfocal, in 511 cases. These lesions were prevailingly extended in sudden cardiac deaths, alcoholic intoxication and electrocution, while in the various kinds of shock, in asphyxia and pesticide poisoning cases they were of a predominantly microfocal nature. According to these morphological changes, the vascular and metabolic factors involved in producing ischaemic cardiomyopathy are discussed."} {"id": "PMID:160989", "title": "Sarcoma of the urinary bladder in the adult. Pathomorphological considerations.", "content": "The author discusses problems of morphological diagnosis and pathogenesis with reference to a case of sarcoma of the urinary bladder presenting the following particularities: exulcerated pedunculate macroscopic aspect, histological leiomyo- and myxosarcomatous differentiation, angiomatous hyperplasia and a late favourable course after partial cystectomy.", "contents": "Sarcoma of the urinary bladder in the adult. Pathomorphological considerations. The author discusses problems of morphological diagnosis and pathogenesis with reference to a case of sarcoma of the urinary bladder presenting the following particularities: exulcerated pedunculate macroscopic aspect, histological leiomyo- and myxosarcomatous differentiation, angiomatous hyperplasia and a late favourable course after partial cystectomy."} {"id": "PMID:160992", "title": "The effect of low temperatures on the viability of Ehrlich ascites tumor cells.", "content": "By using rapid freezing-rapid thawing procedures on Ehrlich ascites tumor cells the authors succeeded in maintaining the viability of these cells, ascertained by two methods: a) trypan blue dye-exclusion test, and b) grafting in experimental animals of cells maintained for three days at -80 degrees C.", "contents": "The effect of low temperatures on the viability of Ehrlich ascites tumor cells. By using rapid freezing-rapid thawing procedures on Ehrlich ascites tumor cells the authors succeeded in maintaining the viability of these cells, ascertained by two methods: a) trypan blue dye-exclusion test, and b) grafting in experimental animals of cells maintained for three days at -80 degrees C."} {"id": "PMID:160988", "title": "Light microscopic observations on fibrous plaque histogenesis in the coronary arteries of children.", "content": "An attempt was made to reconstruct the succession of structural changes which lead to the onset of fibrous plaques in the coronary arteries of children. The results show that certain branch pads or cushions act as precursors of the first fibrous plaques. The conversion of branch pads into atherosclerotic lesions includes edema, histolysis (elastolysis, collagenolysis, ground substance depletion and degenerative cell changes) and in a final step nodular proliferation of smooth muscle cells and abundant neoformation of collagen fibers. This conversion is followed by both reorganization and homogenization of the preexisting heterogeneous microarchitecture. The intermediate steps of pad conversion into atherosclerotic lesions were revealed in 4% of children 1 - 5 years old, 14% of children 6 - 10 years old and 24% of children and juveniles 11 - 15 years old; small, non-raised fibrous plaques were already present in 2% of children 6 - 10 years old and in 4% of children and juveniles 11 - 15 years old.", "contents": "Light microscopic observations on fibrous plaque histogenesis in the coronary arteries of children. An attempt was made to reconstruct the succession of structural changes which lead to the onset of fibrous plaques in the coronary arteries of children. The results show that certain branch pads or cushions act as precursors of the first fibrous plaques. The conversion of branch pads into atherosclerotic lesions includes edema, histolysis (elastolysis, collagenolysis, ground substance depletion and degenerative cell changes) and in a final step nodular proliferation of smooth muscle cells and abundant neoformation of collagen fibers. This conversion is followed by both reorganization and homogenization of the preexisting heterogeneous microarchitecture. The intermediate steps of pad conversion into atherosclerotic lesions were revealed in 4% of children 1 - 5 years old, 14% of children 6 - 10 years old and 24% of children and juveniles 11 - 15 years old; small, non-raised fibrous plaques were already present in 2% of children 6 - 10 years old and in 4% of children and juveniles 11 - 15 years old."} {"id": "PMID:160991", "title": "Effects of the \"reverse\" administration of sexual hormones on the lymph node structure in irradiated Wistar rats.", "content": "The whole-body irradiation of adult Wistar rats with a single dose of 800 r X-rays intensifies the lymph node changes and the decrease of the colloidopexic capacity of hepatosplenic macrophages established by the \"reverse\" administration of sexual hormones. The modifications observed after estradiol administration to the male rat are more marked after a 6 months' interval than those caused in the same interval by testosterone in the female rat lymph nodes.", "contents": "Effects of the \"reverse\" administration of sexual hormones on the lymph node structure in irradiated Wistar rats. The whole-body irradiation of adult Wistar rats with a single dose of 800 r X-rays intensifies the lymph node changes and the decrease of the colloidopexic capacity of hepatosplenic macrophages established by the \"reverse\" administration of sexual hormones. The modifications observed after estradiol administration to the male rat are more marked after a 6 months' interval than those caused in the same interval by testosterone in the female rat lymph nodes."} {"id": "PMID:160993", "title": "Influence of deuterium on the spleen immune system.", "content": "Following administration of deuterium to white rats changes of dysimmunitary-immunitary depression occurred. At the beginning the changes involved the whole spleen parenchyma, with marked lymphocyte depopulation of the red pulp and a decrease of the lymphod follicles. After about 4 - 7 days important amorphous deposits were formed, located exclusively perifollicularly and only in the spleen. The authors suggest the dysimmunitary globulinic-paraamyloidic nature of these deposits which, in their opinion, are produced by deuterium through a chemical mechanism. The differential diagnosis was only made with Gamma-Gandy nodules, because no such changes are found in pathology. It is not known why this deposition takes place exclusively in the spleen and especially around the lymphoid follicles. The authors raise the question whether some methods could be found which might direct the immunitary blockade to certain organs.", "contents": "Influence of deuterium on the spleen immune system. Following administration of deuterium to white rats changes of dysimmunitary-immunitary depression occurred. At the beginning the changes involved the whole spleen parenchyma, with marked lymphocyte depopulation of the red pulp and a decrease of the lymphod follicles. After about 4 - 7 days important amorphous deposits were formed, located exclusively perifollicularly and only in the spleen. The authors suggest the dysimmunitary globulinic-paraamyloidic nature of these deposits which, in their opinion, are produced by deuterium through a chemical mechanism. The differential diagnosis was only made with Gamma-Gandy nodules, because no such changes are found in pathology. It is not known why this deposition takes place exclusively in the spleen and especially around the lymphoid follicles. The authors raise the question whether some methods could be found which might direct the immunitary blockade to certain organs."} {"id": "PMID:160999", "title": "[Circulating immunocomplexes in patients with various morbid conditions].", "content": "The polyethylenglycol (PEG) precipitation technique has been employed for the measurement of immune complexes in the circulation of 100 normal subjects and in 14 patients suffering from a variety of diseases (systemic lupus erythematodes, nephrosic syndrome, cryoglobulinaemia, Buckley's syndrome). Values higher than 0.80 UA on the absorption scale were considered pathological, namely 2 standard deviations above the mean (0.32 UA) in the subjects examined; in the patients, values between a minimum of 0.98 UA and a maximum of 2.38 UA were observed. Longitudinal study of these cases also pointed to the disappearance of immune complexes during therapy. The results suggest that the PEG precipitation technique can play an important part as a screening test in situations in which circulating IC pathology is suspected; it is also a sensitive means of monitoring treatment.", "contents": "[Circulating immunocomplexes in patients with various morbid conditions]. The polyethylenglycol (PEG) precipitation technique has been employed for the measurement of immune complexes in the circulation of 100 normal subjects and in 14 patients suffering from a variety of diseases (systemic lupus erythematodes, nephrosic syndrome, cryoglobulinaemia, Buckley's syndrome). Values higher than 0.80 UA on the absorption scale were considered pathological, namely 2 standard deviations above the mean (0.32 UA) in the subjects examined; in the patients, values between a minimum of 0.98 UA and a maximum of 2.38 UA were observed. Longitudinal study of these cases also pointed to the disappearance of immune complexes during therapy. The results suggest that the PEG precipitation technique can play an important part as a screening test in situations in which circulating IC pathology is suspected; it is also a sensitive means of monitoring treatment."} {"id": "PMID:161000", "title": "Kainic acid binding in human caudate nucleus: effect of Huntington's disease.", "content": "Kainic acid binding was measured in crude membrane fractions prepared from postmortem human caudate tissue of control persons and patients afflicted with Huntington's disease. A significant reduction in binding sites with no change in affinity was found in the Huntington's tissue, the apparent dissociation constants (Kd) and maximal binding (Bmax) values were: 6.4 nM/119 fmol/mg protein (control) and 5.9 nM/53 fmol/mg protein (Huntington). The kainic acid binding showed a remarkable specificity for L-glutamate.", "contents": "Kainic acid binding in human caudate nucleus: effect of Huntington's disease. Kainic acid binding was measured in crude membrane fractions prepared from postmortem human caudate tissue of control persons and patients afflicted with Huntington's disease. A significant reduction in binding sites with no change in affinity was found in the Huntington's tissue, the apparent dissociation constants (Kd) and maximal binding (Bmax) values were: 6.4 nM/119 fmol/mg protein (control) and 5.9 nM/53 fmol/mg protein (Huntington). The kainic acid binding showed a remarkable specificity for L-glutamate."} {"id": "PMID:160994", "title": "In vivo cytogenetic screening for determination of the mutagenic potential of cyclophosphamide.", "content": "Among the in vivo cytogenetic tests employed for chemically induced mutagenicity, a recent screening method was selected - the micronucleus test. The micronuclei were investigated, comparatively with chromosome breaks, on the bone marrow of Wistar rats after intraperitoneal administration of different doses of Cyclophosphamide (CY) applied in one or two injections at 24 hrs interval. The good relationship between these two tests was proved in evaluation of cytogenetic risk.", "contents": "In vivo cytogenetic screening for determination of the mutagenic potential of cyclophosphamide. Among the in vivo cytogenetic tests employed for chemically induced mutagenicity, a recent screening method was selected - the micronucleus test. The micronuclei were investigated, comparatively with chromosome breaks, on the bone marrow of Wistar rats after intraperitoneal administration of different doses of Cyclophosphamide (CY) applied in one or two injections at 24 hrs interval. The good relationship between these two tests was proved in evaluation of cytogenetic risk."} {"id": "PMID:161001", "title": "Barbiturates and calcium-activated adenosine triphosphatase.", "content": "Anaesthetic barbiturates potentiate and convulsant barbiturates inhibit the calcium-activated adenosine triphosphatase (Ca-ATPase) activity in rat brain synaptosomes. Such differential effects and consequent modification of transmitter release may be important in the contrasting actions of these classes of barbiturates in vivo.", "contents": "Barbiturates and calcium-activated adenosine triphosphatase. Anaesthetic barbiturates potentiate and convulsant barbiturates inhibit the calcium-activated adenosine triphosphatase (Ca-ATPase) activity in rat brain synaptosomes. Such differential effects and consequent modification of transmitter release may be important in the contrasting actions of these classes of barbiturates in vivo."} {"id": "PMID:161011", "title": "[Slowed saccades in various neurological disorders].", "content": "4 patients suffering from different neurological disorders are presented, exhibiting a striking slowing down of all saccades. According to their clinical features the problem of slow saccades of supranuclear origin is discussed, to elucidate the question whether these eye movements are saccadic at all. Electro-oculographic traces served to distinguish these particular eye movements, and a computer calculated duration, velocity and acceleration of these saccades, to identify their saccadic nature. 1 patient with Wernicke syndrome showed a remarkable improvement of saccadic velocity following thiamine administration. The findings are reconciled with known saccadic behavior, and a model of the pathophysiological mechanism is cast. The adaptability of the system nearly back to normal in the case of Wernicke syndrome is stressed.", "contents": "[Slowed saccades in various neurological disorders]. 4 patients suffering from different neurological disorders are presented, exhibiting a striking slowing down of all saccades. According to their clinical features the problem of slow saccades of supranuclear origin is discussed, to elucidate the question whether these eye movements are saccadic at all. Electro-oculographic traces served to distinguish these particular eye movements, and a computer calculated duration, velocity and acceleration of these saccades, to identify their saccadic nature. 1 patient with Wernicke syndrome showed a remarkable improvement of saccadic velocity following thiamine administration. The findings are reconciled with known saccadic behavior, and a model of the pathophysiological mechanism is cast. The adaptability of the system nearly back to normal in the case of Wernicke syndrome is stressed."} {"id": "PMID:161018", "title": "[Laboratory methods of examination of porous vascular prostheses].", "content": "The author discusses applied methods of investigation of porous vascular prostheses with special attention to physical methods and proposes some heretofore unused criteria for the evaluation of polyester prostheses such as: quantitative determination of oligomers catalist residues, inor ganic fillers and manufacturer's oil and identification of the degree of crystallization and molecular orientation. The evaluation of these parameters in conjunction with the results of physical, mechanical, hematological, toxicologic and preclinical testing may form the basis for further improvement of vascular prostheses.", "contents": "[Laboratory methods of examination of porous vascular prostheses]. The author discusses applied methods of investigation of porous vascular prostheses with special attention to physical methods and proposes some heretofore unused criteria for the evaluation of polyester prostheses such as: quantitative determination of oligomers catalist residues, inor ganic fillers and manufacturer's oil and identification of the degree of crystallization and molecular orientation. The evaluation of these parameters in conjunction with the results of physical, mechanical, hematological, toxicologic and preclinical testing may form the basis for further improvement of vascular prostheses."} {"id": "PMID:161025", "title": "The effects of dietary niacin and riboflavin on voluntary intake and metabolism of ethanol in rats.", "content": "The effects of dietary deficiency and excess of niacin and riboflavin on voluntary drinking of 10% (v/v) ethanol were studied in male rats. The effectiveness of dietary deficiency and excess of both niacin and riboflavin on tissue levels of these vitamins was demonstrated by measurements of urinary N1-methylnicotinamide and blood glutathione reductase (EC 1.6.4.2) activity. A high-niacin diet containing 75 mg niacin/kg food decreased ethanol intake by about 36% compared to the control diet containing 15 mgniacin/kg. Niacin or riboflavin deficiency and a high-riboflavin diet containing 40 mg rtary levels of niacin or riboflavin did not influence on ethanol elimination rate or levels of blood acetaldehyde during ethanol oxidation. Therefore, blood acetaldehyde was not responsible for the decreased ethanol intake of rats fed with a high-niacin diet. It was concluded that the increased ethanol intake caused by dietary deprivation of B-vitamin complex found in earlier studies is not a result of deficiency of niacin or riboflavin but niacin may be involved in the decrease in ethanol drinking, which follows dietary B-vitamin complex supplementation.", "contents": "The effects of dietary niacin and riboflavin on voluntary intake and metabolism of ethanol in rats. The effects of dietary deficiency and excess of niacin and riboflavin on voluntary drinking of 10% (v/v) ethanol were studied in male rats. The effectiveness of dietary deficiency and excess of both niacin and riboflavin on tissue levels of these vitamins was demonstrated by measurements of urinary N1-methylnicotinamide and blood glutathione reductase (EC 1.6.4.2) activity. A high-niacin diet containing 75 mg niacin/kg food decreased ethanol intake by about 36% compared to the control diet containing 15 mgniacin/kg. Niacin or riboflavin deficiency and a high-riboflavin diet containing 40 mg rtary levels of niacin or riboflavin did not influence on ethanol elimination rate or levels of blood acetaldehyde during ethanol oxidation. Therefore, blood acetaldehyde was not responsible for the decreased ethanol intake of rats fed with a high-niacin diet. It was concluded that the increased ethanol intake caused by dietary deprivation of B-vitamin complex found in earlier studies is not a result of deficiency of niacin or riboflavin but niacin may be involved in the decrease in ethanol drinking, which follows dietary B-vitamin complex supplementation."} {"id": "PMID:161026", "title": "The measurement of cerebrospinal fluid flow.", "content": "A technique for the measurement of cerebrospinal fluid (CSF) velocity-flow is described. It enables the flow of CSF in response to pressure pulses to be measured whilst allowing the simultaneous measurement of pressure through a lumber puncture needle. The physical principles which govern the operation of the flow probe are presented together with practical forms of the probe. The application of the technique is demonstrated by experiments on dog.", "contents": "The measurement of cerebrospinal fluid flow. A technique for the measurement of cerebrospinal fluid (CSF) velocity-flow is described. It enables the flow of CSF in response to pressure pulses to be measured whilst allowing the simultaneous measurement of pressure through a lumber puncture needle. The physical principles which govern the operation of the flow probe are presented together with practical forms of the probe. The application of the technique is demonstrated by experiments on dog."} {"id": "PMID:161027", "title": "Digestive structural modifications in rats submitted to 15 days of hypokinetical conditions.", "content": "Restraining rats for 14 days in special cages in order to determine a hypokinetical state decreased mucopolysaccharide secretion in submaxillary glands and gastric mucosa. In the small intestine and in the colon, concomitantly with an enzymatic (leucine-aminopeptidase and acid phosphatase) hypersecretion as results from specific histochemical reactions. These modifications show maximum intensity at the end of the interval. The corticosterone plasmatic level determined in the same interval also increased, suggesting this way to a causal relation. The histomorphological changes presented delayed reaction. This material is in accord with our previous investigations as well as with some literature data.", "contents": "Digestive structural modifications in rats submitted to 15 days of hypokinetical conditions. Restraining rats for 14 days in special cages in order to determine a hypokinetical state decreased mucopolysaccharide secretion in submaxillary glands and gastric mucosa. In the small intestine and in the colon, concomitantly with an enzymatic (leucine-aminopeptidase and acid phosphatase) hypersecretion as results from specific histochemical reactions. These modifications show maximum intensity at the end of the interval. The corticosterone plasmatic level determined in the same interval also increased, suggesting this way to a causal relation. The histomorphological changes presented delayed reaction. This material is in accord with our previous investigations as well as with some literature data."} {"id": "PMID:161040", "title": "[Postero-lateral bone grafting in the lumbar and lumbo-sacral spine (author's transl)].", "content": "78 arthrodeses of the lumbar and lumbo-sacral region were performed by a postero-lateral approach. The technique is described and the results. The patients were reviewed after an average follow-up of 4 years. Fusion was obtained in 83 p. 100 of cases. The operation was performed for low back pain, spondylolisthesis, or lumbar arthrosis. Indications are discussed in relation to the etiology.", "contents": "[Postero-lateral bone grafting in the lumbar and lumbo-sacral spine (author's transl)]. 78 arthrodeses of the lumbar and lumbo-sacral region were performed by a postero-lateral approach. The technique is described and the results. The patients were reviewed after an average follow-up of 4 years. Fusion was obtained in 83 p. 100 of cases. The operation was performed for low back pain, spondylolisthesis, or lumbar arthrosis. Indications are discussed in relation to the etiology."} {"id": "PMID:161041", "title": "[The prediction of growth in long bones in poliomyelitis (author's transl)].", "content": "The authors have studied 15 cases of unilateral poliomyelitis and have compared the growth of the intact lower limb with that of the paralysed limb. It is concluded that no accurate prediction can be made except by multiple measurements. In most of the cases, growth was steady, the rate of shortening increasing by regular degrees. However, in very young children the degree of shortening was more consistent and was similar to that in congenital abnormalities.", "contents": "[The prediction of growth in long bones in poliomyelitis (author's transl)]. The authors have studied 15 cases of unilateral poliomyelitis and have compared the growth of the intact lower limb with that of the paralysed limb. It is concluded that no accurate prediction can be made except by multiple measurements. In most of the cases, growth was steady, the rate of shortening increasing by regular degrees. However, in very young children the degree of shortening was more consistent and was similar to that in congenital abnormalities."} {"id": "PMID:161042", "title": "[Subtalar dislocations with medial or lateral displacement (author's transl)].", "content": "The authors have observed 20 cases of subtalar dislocation, 16 with medial displacement and 4 with lateral displacement. The treatment given and the results are described. An experimental study has also been made which confirms that in medial dislocations the talo-navicular joint dislocates first whilst in lateral dislocations the talo-navicular joint dislocates last. The severity of assoicated lesions is emphasised. It is concluded that in severe displacement with complete extrusion of the talus, tibio-calcaneal arthrodesis gave better results than excision of the talus.", "contents": "[Subtalar dislocations with medial or lateral displacement (author's transl)]. The authors have observed 20 cases of subtalar dislocation, 16 with medial displacement and 4 with lateral displacement. The treatment given and the results are described. An experimental study has also been made which confirms that in medial dislocations the talo-navicular joint dislocates first whilst in lateral dislocations the talo-navicular joint dislocates last. The severity of assoicated lesions is emphasised. It is concluded that in severe displacement with complete extrusion of the talus, tibio-calcaneal arthrodesis gave better results than excision of the talus."} {"id": "PMID:161043", "title": "[Odontoid process fractures associated with fractures of the pedicles of the axis (author's transl)].", "content": "The authors report their experience concerning eleven cases of that original and frequent association of fractures. The ligamentous lesions associated with those fractures are considered, justifying the necessary dynamic X rays. The eleven cases are reviewed and a classification supported by an iconography is given, according to the unstability of the odontoid or of the pedicles. The complications after orthopaedic or surgical treatment are analysed and the authors give their conclusions. The proposed treatment is conservative when the fractures are neither displaced nor unstable, and surgical when one of the two fractures is unstable. The best procedure is bi-pedicular screwing associated with C1/C2 wiring.", "contents": "[Odontoid process fractures associated with fractures of the pedicles of the axis (author's transl)]. The authors report their experience concerning eleven cases of that original and frequent association of fractures. The ligamentous lesions associated with those fractures are considered, justifying the necessary dynamic X rays. The eleven cases are reviewed and a classification supported by an iconography is given, according to the unstability of the odontoid or of the pedicles. The complications after orthopaedic or surgical treatment are analysed and the authors give their conclusions. The proposed treatment is conservative when the fractures are neither displaced nor unstable, and surgical when one of the two fractures is unstable. The best procedure is bi-pedicular screwing associated with C1/C2 wiring."} {"id": "PMID:161044", "title": "[Arthrodesis of the ankle. A study of the complications and long term results (author's transl)].", "content": "The authors have studied the complications and long term results of 91 cases of tibio-talar arthrodesis and 43 cases of tibio-talar arthrodesis associated with subtalar arthrodesis. Minor complications such as limited skin necrosis were noted in 13 p. 100 of the cases, and no-fusion occurred in 7 p. 100. The results were satisfactory in 75 p. 100 of the cases, fair in 13 p. 100, poor in 12 p. 100. Most of the poor results were related to painfull subtalar joints after isolated tibio-talar arthrodesis. This happened often following conditions : excessive equinus, protrusion of screws in the subtalar joint, preoperative lesions of the subtalar joint. In cases of associated tibio-tarsal and subtalar arthrodesis, the long term study revealed moderate and painless secondary arthrosis of the mid-tarsal joint. It is concluded that associated fusion of the subtalar joint should always be considered when tibio-talar arthrodesis is indicated.", "contents": "[Arthrodesis of the ankle. A study of the complications and long term results (author's transl)]. The authors have studied the complications and long term results of 91 cases of tibio-talar arthrodesis and 43 cases of tibio-talar arthrodesis associated with subtalar arthrodesis. Minor complications such as limited skin necrosis were noted in 13 p. 100 of the cases, and no-fusion occurred in 7 p. 100. The results were satisfactory in 75 p. 100 of the cases, fair in 13 p. 100, poor in 12 p. 100. Most of the poor results were related to painfull subtalar joints after isolated tibio-talar arthrodesis. This happened often following conditions : excessive equinus, protrusion of screws in the subtalar joint, preoperative lesions of the subtalar joint. In cases of associated tibio-tarsal and subtalar arthrodesis, the long term study revealed moderate and painless secondary arthrosis of the mid-tarsal joint. It is concluded that associated fusion of the subtalar joint should always be considered when tibio-talar arthrodesis is indicated."} {"id": "PMID:161045", "title": "[Fracture of the coracoid process (author's transl)].", "content": "The authors have treated 10 cases of fracture of the coracoid process of the scapula. The case histories have been reviewed. The mechanism was an indirect one in most cases. Associated lesions such as fractures of the clavicle were frequent. The diagnosis may be difficult and special X-ray techniques were needed. In most of the cases, conservative treatment was indicated. Only one case associated with an acromio-clavicular dislocation was treated operatively.", "contents": "[Fracture of the coracoid process (author's transl)]. The authors have treated 10 cases of fracture of the coracoid process of the scapula. The case histories have been reviewed. The mechanism was an indirect one in most cases. Associated lesions such as fractures of the clavicle were frequent. The diagnosis may be difficult and special X-ray techniques were needed. In most of the cases, conservative treatment was indicated. Only one case associated with an acromio-clavicular dislocation was treated operatively."} {"id": "PMID:161047", "title": "[Regeneration of a diaphyseal segment of the radius (author's transl)].", "content": "The osteogenesis potential and the subsequent skeleton reconstruction are well known in young children. Our case illustrate these two features. A six years old patient had lost the entire radial diaphysis during an open trauma of the forearm ; after the debridement of the wound, the limb was simply immobilized in a cast leaving off the radial diaphysis. Six months later an antomical reconstruction of the radius was obtained with a very good function.", "contents": "[Regeneration of a diaphyseal segment of the radius (author's transl)]. The osteogenesis potential and the subsequent skeleton reconstruction are well known in young children. Our case illustrate these two features. A six years old patient had lost the entire radial diaphysis during an open trauma of the forearm ; after the debridement of the wound, the limb was simply immobilized in a cast leaving off the radial diaphysis. Six months later an antomical reconstruction of the radius was obtained with a very good function."} {"id": "PMID:161046", "title": "[Tumour-like bone manifestations in Hodgkin's disease. A report of two cases (author's transl)].", "content": "Two cases are reported in which the diagnosis of Hodgkin's Disease was revealed after a bone biopsy of an apparently primary lesion. In fact, the disease was already generalised and the authors question the existence of purely osseous varieties of the disease. Of the two reported cases, one died rapidly and the other had a long-term remission.", "contents": "[Tumour-like bone manifestations in Hodgkin's disease. A report of two cases (author's transl)]. Two cases are reported in which the diagnosis of Hodgkin's Disease was revealed after a bone biopsy of an apparently primary lesion. In fact, the disease was already generalised and the authors question the existence of purely osseous varieties of the disease. Of the two reported cases, one died rapidly and the other had a long-term remission."} {"id": "PMID:161056", "title": "[Treatment of Paget's disease paraplegia with diphosphonates : preliminary results (author's transl)].", "content": "The authors describe the results of treatment of four cases of spasmodic paraplegia from Paget's disease of the vertebrae with diphosphonates (EHDP and CL2 MDP). The quality and long duration of the functional results obtained by this new treatment of Paget's disease indicate that medical treatment is essential for the medullary complications of this affection.", "contents": "[Treatment of Paget's disease paraplegia with diphosphonates : preliminary results (author's transl)]. The authors describe the results of treatment of four cases of spasmodic paraplegia from Paget's disease of the vertebrae with diphosphonates (EHDP and CL2 MDP). The quality and long duration of the functional results obtained by this new treatment of Paget's disease indicate that medical treatment is essential for the medullary complications of this affection."} {"id": "PMID:161057", "title": "[Aneurysmal vertebra cyst (observation on two cases with neurological findings) (author's transl)].", "content": "The authors report 2 cases of aneurysmal cysts of the spinal cord with neurological manifestations. The first case was a young girl of 16 years of age with a lesion at the D6 level and spasmodic paraparesis. The second case was a boy aged 5 years with a lesions at the L3 level and lumbar pains. The characteristic \"one-eyed vertebra\" appearance was present in the radiological images in both cases, and was confirmed histologically on operation, which produced good results.", "contents": "[Aneurysmal vertebra cyst (observation on two cases with neurological findings) (author's transl)]. The authors report 2 cases of aneurysmal cysts of the spinal cord with neurological manifestations. The first case was a young girl of 16 years of age with a lesion at the D6 level and spasmodic paraparesis. The second case was a boy aged 5 years with a lesions at the L3 level and lumbar pains. The characteristic \"one-eyed vertebra\" appearance was present in the radiological images in both cases, and was confirmed histologically on operation, which produced good results."} {"id": "PMID:161058", "title": "A review of spontaneously reported adverse drug reactions with diclofenac sodium (Voltarol).", "content": "The author reviews the worldwide picture of adverse reactions reported with diclofenac during the four-year period ending in December 1977, at which point he estimates that some ten million patients had received treatment with the drug. A total of 447 unwanted effects were reported in 194 patients, the most frequently reported side-effects being gastrointestinal in nature, followed by dermatological and central nervous system effects. Thirteen cases of liver function abnormality were reported, although there was reason to believe that 11 of these were not ascribable to diclofenac. Twenty haematological effects were reported, including two cases of agranulocytosis and two cases of fatal aplastic anaemia; one patient in each of these groups was taking concomitant pyrazolone compounds. Evaluation of adverse reactions reported with diclofenac suggest a profile in which gastrointestinal side-effects predominate; however, the risk of serious side-effects of this nature is slight, and the impression of good tolerability which emerges from this review is confirmed by the findings of comparative clinical trials.", "contents": "A review of spontaneously reported adverse drug reactions with diclofenac sodium (Voltarol). The author reviews the worldwide picture of adverse reactions reported with diclofenac during the four-year period ending in December 1977, at which point he estimates that some ten million patients had received treatment with the drug. A total of 447 unwanted effects were reported in 194 patients, the most frequently reported side-effects being gastrointestinal in nature, followed by dermatological and central nervous system effects. Thirteen cases of liver function abnormality were reported, although there was reason to believe that 11 of these were not ascribable to diclofenac. Twenty haematological effects were reported, including two cases of agranulocytosis and two cases of fatal aplastic anaemia; one patient in each of these groups was taking concomitant pyrazolone compounds. Evaluation of adverse reactions reported with diclofenac suggest a profile in which gastrointestinal side-effects predominate; however, the risk of serious side-effects of this nature is slight, and the impression of good tolerability which emerges from this review is confirmed by the findings of comparative clinical trials."} {"id": "PMID:161062", "title": "[Therapeutic approach in the rehabilitation of chronic lower back pain. Comparative study of 3 techniques of lumbar reeducation].", "content": "The short-term therapeutic effect of 3 techniques of rehabilitation of the lumbar spine (cyphosis gymnastics, kinebalneotherapy and differenciated rehabilitation) was studied out of 87 chronic lumbalgias selected at random and using one of the three techniques administered by 3 physical therapists. A comparison of these 9 couples (technique, technician) was based on criteria evaluated on a blind basis using the traditional unidimensional analysis and also multidimensional analysis. The cyphosis gymnastic reeducation gives less satisfactory results using 26 criteria out of 27. There is an underlying physical therapy factor. A certain number of prognostic factors with implications for any rehabilitation method and for all of the techniques, were disclosed. The comparative testing methods used in the study of drugs are applicable to rehabilitation techniques. However, it was not possible to carry out a comparative study of a reeducation method with a reeducation placebo.", "contents": "[Therapeutic approach in the rehabilitation of chronic lower back pain. Comparative study of 3 techniques of lumbar reeducation]. The short-term therapeutic effect of 3 techniques of rehabilitation of the lumbar spine (cyphosis gymnastics, kinebalneotherapy and differenciated rehabilitation) was studied out of 87 chronic lumbalgias selected at random and using one of the three techniques administered by 3 physical therapists. A comparison of these 9 couples (technique, technician) was based on criteria evaluated on a blind basis using the traditional unidimensional analysis and also multidimensional analysis. The cyphosis gymnastic reeducation gives less satisfactory results using 26 criteria out of 27. There is an underlying physical therapy factor. A certain number of prognostic factors with implications for any rehabilitation method and for all of the techniques, were disclosed. The comparative testing methods used in the study of drugs are applicable to rehabilitation techniques. However, it was not possible to carry out a comparative study of a reeducation method with a reeducation placebo."} {"id": "PMID:161063", "title": "[In vitro study of the primary antibody response of circulating lymphocytes in patients with chronic inflammatory rheumatism].", "content": "We have studied the in vitro antibody response to a hapten of peripheral blood lymphocytes from 26 patients with rheumatoid arthritis and 7 ankylosing spondylitis. These patients had never received immunosuppressor drugs before or corticosteroids during the month before the test. They had failed to receive aspirin or non-steroid anti-inflammatory drugs for 72 hours before blood sampling. The control groups included respectively 38 healthy subjects and 24 patients hospitalized for non inflammatory disease. The antibody response of ankylosing spondylitis patients is comparable to that of controls ; on the opposite the response of patients with rhumatoid arthritis is significantly depressed in comparison with the three other groups. The weak response of lymphocytes in arthritis is not due to increased cell death in culture or to modified kinetics of the antibody response or to the appearance of a IgG secondary type response or a in vivo pre-activation. The lymphocytes of arthritis patients do not inhibit the response of normal lymphocytes when they are co-cultured. The observed response is identical to that obtained when control patient lymphocytes are co-cultured with normal lymphocytes. The function of suppressor T cells induced by Con A seems normal in spondylitis and arthritis.", "contents": "[In vitro study of the primary antibody response of circulating lymphocytes in patients with chronic inflammatory rheumatism]. We have studied the in vitro antibody response to a hapten of peripheral blood lymphocytes from 26 patients with rheumatoid arthritis and 7 ankylosing spondylitis. These patients had never received immunosuppressor drugs before or corticosteroids during the month before the test. They had failed to receive aspirin or non-steroid anti-inflammatory drugs for 72 hours before blood sampling. The control groups included respectively 38 healthy subjects and 24 patients hospitalized for non inflammatory disease. The antibody response of ankylosing spondylitis patients is comparable to that of controls ; on the opposite the response of patients with rhumatoid arthritis is significantly depressed in comparison with the three other groups. The weak response of lymphocytes in arthritis is not due to increased cell death in culture or to modified kinetics of the antibody response or to the appearance of a IgG secondary type response or a in vivo pre-activation. The lymphocytes of arthritis patients do not inhibit the response of normal lymphocytes when they are co-cultured. The observed response is identical to that obtained when control patient lymphocytes are co-cultured with normal lymphocytes. The function of suppressor T cells induced by Con A seems normal in spondylitis and arthritis."} {"id": "PMID:161064", "title": "LEg venous oxygen saturation in the evaluation of intra-operative blood flow during arterial reconstructive surgery.", "content": "In twenty-four patients, undergoing a femoro-popliteal saphenous vein bypass graft for symptomatic atherosclerotic occlusion of the superficial femoral artery, oxygen saturation values for the femoral and popliteal veins were compared to the directly measured blood flows in the common femoral artery and in the bypass graft, respectively. Blood flow and venous oxygen saturation increased significantly after transfusion of 900 ml of blood. Pharmacological vasodilation caused a significant increase in blood flow both before and after transfusion, whereas the changes in venous oxygen saturation were significant only before blood transfusion. A close statistical relationship was found between initial femoral venous oxygen saturation and initial blood flow in the common femoral artery as well as between initial popliteal venous oxygen saturation and initial byapss blood flow. However, especially at low saturation values, the evaluation of blood flow was very uncertain. Whole leg and lower leg oxygen uptakes were not altered by intraoperative changes in blood volume. It is concluded that blood flow in the common femoral artery and the bypass graft can be roughly estimated from analysis of oxygen saturation in the femoral and popliteal veins, respectively. Furthermore, by determining leg venous oxygen saturation both before and after flow augmentation, induced by pharmacological vasodilation, a conception of the load on the vascular system may be obtained.", "contents": "LEg venous oxygen saturation in the evaluation of intra-operative blood flow during arterial reconstructive surgery. In twenty-four patients, undergoing a femoro-popliteal saphenous vein bypass graft for symptomatic atherosclerotic occlusion of the superficial femoral artery, oxygen saturation values for the femoral and popliteal veins were compared to the directly measured blood flows in the common femoral artery and in the bypass graft, respectively. Blood flow and venous oxygen saturation increased significantly after transfusion of 900 ml of blood. Pharmacological vasodilation caused a significant increase in blood flow both before and after transfusion, whereas the changes in venous oxygen saturation were significant only before blood transfusion. A close statistical relationship was found between initial femoral venous oxygen saturation and initial blood flow in the common femoral artery as well as between initial popliteal venous oxygen saturation and initial byapss blood flow. However, especially at low saturation values, the evaluation of blood flow was very uncertain. Whole leg and lower leg oxygen uptakes were not altered by intraoperative changes in blood volume. It is concluded that blood flow in the common femoral artery and the bypass graft can be roughly estimated from analysis of oxygen saturation in the femoral and popliteal veins, respectively. Furthermore, by determining leg venous oxygen saturation both before and after flow augmentation, induced by pharmacological vasodilation, a conception of the load on the vascular system may be obtained."} {"id": "PMID:161065", "title": "Lack of suppressor cell activity in rheumatoid synovial lymphocytes.", "content": "Lymphocytes were eluted from the synovial tissue of seventeen patients with rheumatoid arthritis (RA) and one with ankylosing spondylitis. In eight of these patients immunoglobulin production by synovial lymphocytes in the presence and absence of pokeweed mitogen was studied. In nine patients T lymphocytes were isolated from the eluted cells, and the T helper and suppressor cell functions were evaluated in an allogeneic co-culture system. Peripheral blood lymphocytes (PBL) from twenty-eight normal donors were also studied for comparison. Immunoglobulin produced by synovial lymphocytes was higher than in PBL of normal donors. However, the stimulation index of synovial tissue lymphocytes was lower. Most of the normal donors had suppressor cell activity in their peripheral blood, whereas in synovial tissue lymphocytes a statistically significant number of patients did not have any suppressor cell activity. In contrast, the synovial tissue lymphocytes showed helper activity not differing significantly from that of the T lymphocytes from peripheral blood of normal individuals.", "contents": "Lack of suppressor cell activity in rheumatoid synovial lymphocytes. Lymphocytes were eluted from the synovial tissue of seventeen patients with rheumatoid arthritis (RA) and one with ankylosing spondylitis. In eight of these patients immunoglobulin production by synovial lymphocytes in the presence and absence of pokeweed mitogen was studied. In nine patients T lymphocytes were isolated from the eluted cells, and the T helper and suppressor cell functions were evaluated in an allogeneic co-culture system. Peripheral blood lymphocytes (PBL) from twenty-eight normal donors were also studied for comparison. Immunoglobulin produced by synovial lymphocytes was higher than in PBL of normal donors. However, the stimulation index of synovial tissue lymphocytes was lower. Most of the normal donors had suppressor cell activity in their peripheral blood, whereas in synovial tissue lymphocytes a statistically significant number of patients did not have any suppressor cell activity. In contrast, the synovial tissue lymphocytes showed helper activity not differing significantly from that of the T lymphocytes from peripheral blood of normal individuals."} {"id": "PMID:161070", "title": "Evaluation of manipulation and other manual therapy. Criteria for measuring the effect of treatment.", "content": "In order to evaluate manipulation and other methods of manual therapy, the literature was reviewed. It was found that the number of publications based on scientific criteria is rather limited. However, with certain reservations it can be concluded that manipulation of the lumbar spine might have an immediate, short-time effect on low back pain in a limited number of patients. The criteria for selection, however, cannot be defined on the basis of the available material. Manipulation has no superior long-term effect as compared to other methods of treatment. The effect of specific, non-manipulative mobilization of the cervical and lumbar spine needs further elucidation. Manual therapy in decreased mobility of the extremity joints has received support from control studies.", "contents": "Evaluation of manipulation and other manual therapy. Criteria for measuring the effect of treatment. In order to evaluate manipulation and other methods of manual therapy, the literature was reviewed. It was found that the number of publications based on scientific criteria is rather limited. However, with certain reservations it can be concluded that manipulation of the lumbar spine might have an immediate, short-time effect on low back pain in a limited number of patients. The criteria for selection, however, cannot be defined on the basis of the available material. Manipulation has no superior long-term effect as compared to other methods of treatment. The effect of specific, non-manipulative mobilization of the cervical and lumbar spine needs further elucidation. Manual therapy in decreased mobility of the extremity joints has received support from control studies."} {"id": "PMID:161072", "title": "[Immunohistologic findings in patients with myocardial hypertrophy].", "content": "Heart reactive antibodies have been found with direct and indirect immunofluorescence in patients with congestive cardiomyopathy. The authors therefore investigated by direct immunofluorescence 25 patients with aortic valve disease and 11 patients with congestive cardiomyopathy who underwent diagnostic heart catheterization and left ventricular endomyocardial biopsy. The left ventricular biopsies were fixed by bouin, formaline and freeze-drying. A first analysis was performed to determine auto- or formaline-induced fluorescence. A second analysis was performed to identify myocardial structures with positive fluorescence using 5 different anti-sera or patient's serum. The results showed positive fluorescence with anti-IgG-antibodies in patients with aortic valve disease (23%) and with congestive cardiomyopathy (73%). The immunoglobulin deposits were located mainly in the subendocardial connective tissue. These deposits showed also slight fluorescence with anti-IgM, anti-C1q and anti-C4 antibodies. However, a correlation between the hemodynamic and immunologic findings was not demonstrated. It is concluded that the myocardial immune complexes appear to be reactive and do not play an essential role in the pathogenesis of congestive cardiomyopathy.", "contents": "[Immunohistologic findings in patients with myocardial hypertrophy]. Heart reactive antibodies have been found with direct and indirect immunofluorescence in patients with congestive cardiomyopathy. The authors therefore investigated by direct immunofluorescence 25 patients with aortic valve disease and 11 patients with congestive cardiomyopathy who underwent diagnostic heart catheterization and left ventricular endomyocardial biopsy. The left ventricular biopsies were fixed by bouin, formaline and freeze-drying. A first analysis was performed to determine auto- or formaline-induced fluorescence. A second analysis was performed to identify myocardial structures with positive fluorescence using 5 different anti-sera or patient's serum. The results showed positive fluorescence with anti-IgG-antibodies in patients with aortic valve disease (23%) and with congestive cardiomyopathy (73%). The immunoglobulin deposits were located mainly in the subendocardial connective tissue. These deposits showed also slight fluorescence with anti-IgM, anti-C1q and anti-C4 antibodies. However, a correlation between the hemodynamic and immunologic findings was not demonstrated. It is concluded that the myocardial immune complexes appear to be reactive and do not play an essential role in the pathogenesis of congestive cardiomyopathy."} {"id": "PMID:161073", "title": "[Effect of 2 phosphonates on the osteolysis induced by tumor extracts].", "content": "An in-vitro model is proposed to test the potential effect of diphosphonates in treatment or preventing bone metastases. This model involves culturing of neonatal mice calvaria in sterile conditions in an appropriate medium and measuring 45Ca release from bone to medium, the mice being injected with 45Ca on the day of birth. Tumour extracts added to the medium usually increase the bone lysis; this effect is significantly decreased when the mice have been treated with either ethane-hydroxy-diphosphonate (EHDP) or dichloromethylene-diphosphonate (Cl2MDP). These experiments represent a first step in a group of experiments with a view to clinical trials in cases of bone metastases.", "contents": "[Effect of 2 phosphonates on the osteolysis induced by tumor extracts]. An in-vitro model is proposed to test the potential effect of diphosphonates in treatment or preventing bone metastases. This model involves culturing of neonatal mice calvaria in sterile conditions in an appropriate medium and measuring 45Ca release from bone to medium, the mice being injected with 45Ca on the day of birth. Tumour extracts added to the medium usually increase the bone lysis; this effect is significantly decreased when the mice have been treated with either ethane-hydroxy-diphosphonate (EHDP) or dichloromethylene-diphosphonate (Cl2MDP). These experiments represent a first step in a group of experiments with a view to clinical trials in cases of bone metastases."} {"id": "PMID:161074", "title": "Induced pain referral from posterior lumbar elements in normal subjects.", "content": "Patterns of pain referral, induced from the posterior elements, have been studied in normal volunteer subjects. A series of intracapsular and pericapsular injections were performed at the L1-2 and L4-5 levels. The areas of pain referral indicate overlap between the upper and lower lumbar spine. It is also shown that the pericapsular and intrafacetal pain referral areas are similar and that the upper lumbar spine is more sensitive than the lower.", "contents": "Induced pain referral from posterior lumbar elements in normal subjects. Patterns of pain referral, induced from the posterior elements, have been studied in normal volunteer subjects. A series of intracapsular and pericapsular injections were performed at the L1-2 and L4-5 levels. The areas of pain referral indicate overlap between the upper and lower lumbar spine. It is also shown that the pericapsular and intrafacetal pain referral areas are similar and that the upper lumbar spine is more sensitive than the lower."} {"id": "PMID:161075", "title": "The pharmacologic approach in differential diagnosis of chronic pain.", "content": "Chronic pain of unknown cause below waist level was evaluated in 100 patients by using the Differential Spinal Block (DSB) in a multidisciplinary pain clinic setting. The classic DSB approach, refined for better control of psychologic variables, was found to be a safe and effective means of differentiating various pain mechanisms. We found that, of all patients tested, 55% had pain of central or psychogenic origin and 30% had sympathetically mediated pain, as compared with 15% who had somatic pain. A long-term follow-up of these patients confirmed this impression. These results substantiated the importance of psychologic variables, in dicating the necessity for use of behavioral-based therapies in conjunction with the routine use of the refined diagnostic DSB procedure in patients with chronic pain.", "contents": "The pharmacologic approach in differential diagnosis of chronic pain. Chronic pain of unknown cause below waist level was evaluated in 100 patients by using the Differential Spinal Block (DSB) in a multidisciplinary pain clinic setting. The classic DSB approach, refined for better control of psychologic variables, was found to be a safe and effective means of differentiating various pain mechanisms. We found that, of all patients tested, 55% had pain of central or psychogenic origin and 30% had sympathetically mediated pain, as compared with 15% who had somatic pain. A long-term follow-up of these patients confirmed this impression. These results substantiated the importance of psychologic variables, in dicating the necessity for use of behavioral-based therapies in conjunction with the routine use of the refined diagnostic DSB procedure in patients with chronic pain."} {"id": "PMID:161080", "title": "Plastic reconstruction after bypass surgery and massive weight loss.", "content": "In summary, the surgical techniques described can provide substantial benefit to selected patients who have sustained massive weight loss. As in all cosmetic surgery, patient selection must be meticulous. The expectations of the patient must be realistic, and the very real risks of the operative procedures must be understood. Patients who have sustained massive weight loss should be informed of the possibilities of reconstructive plastic surgery.", "contents": "Plastic reconstruction after bypass surgery and massive weight loss. In summary, the surgical techniques described can provide substantial benefit to selected patients who have sustained massive weight loss. As in all cosmetic surgery, patient selection must be meticulous. The expectations of the patient must be realistic, and the very real risks of the operative procedures must be understood. Patients who have sustained massive weight loss should be informed of the possibilities of reconstructive plastic surgery."} {"id": "PMID:161076", "title": "An analysis of differential epidural spinal anesthesia and pentothal pain study in the differential diagnosis of back pain. Aids in avoiding unnecessary back surgery.", "content": "The selection of the proper patient for back surgery is of prime importance and is the topic of this report. An analysis of patients evaluated with differential epidural spinal anesthesia and the Pentothal pain study show these tests to be helpful in separating those patients with primarily organic pain who could benefit from surgery from those patients with primarily functional pain who should not be operated upon. These tests will help one determine whether a disability is related to the severity of pain, to the patient's emotional response to pain, or to a somatic manifestation of a gross emotional breakdown.", "contents": "An analysis of differential epidural spinal anesthesia and pentothal pain study in the differential diagnosis of back pain. Aids in avoiding unnecessary back surgery. The selection of the proper patient for back surgery is of prime importance and is the topic of this report. An analysis of patients evaluated with differential epidural spinal anesthesia and the Pentothal pain study show these tests to be helpful in separating those patients with primarily organic pain who could benefit from surgery from those patients with primarily functional pain who should not be operated upon. These tests will help one determine whether a disability is related to the severity of pain, to the patient's emotional response to pain, or to a somatic manifestation of a gross emotional breakdown."} {"id": "PMID:161079", "title": "Pharyngeal infection with Neisseria gonorrhoeae.", "content": "During 1978, 156 patients were treated for pharyngeal infection with Neisseria gonorrhoeae; 115 (74%) returned for a posttreatment culture. Aqueous procaine penicillin G (4.8 X 10(6) units) given im with (19 patients) or without (64 patients) orally administered ampicillin for four days was successful therapy in 86% of instances. All seven patients who received tetracycline hydrochloride orally for five days had negative posttreatment cultures, as did nine of 12 patients who received 2.0 g (four patients) or 4.0 g (eight patients) of spectinomycin hydrochloride, im. Concurrent anogenital infection with N. gonorrhoeae was documented for about 60% of the patients, and, with one exception, was eradicated by these treatment schedules.", "contents": "Pharyngeal infection with Neisseria gonorrhoeae. During 1978, 156 patients were treated for pharyngeal infection with Neisseria gonorrhoeae; 115 (74%) returned for a posttreatment culture. Aqueous procaine penicillin G (4.8 X 10(6) units) given im with (19 patients) or without (64 patients) orally administered ampicillin for four days was successful therapy in 86% of instances. All seven patients who received tetracycline hydrochloride orally for five days had negative posttreatment cultures, as did nine of 12 patients who received 2.0 g (four patients) or 4.0 g (eight patients) of spectinomycin hydrochloride, im. Concurrent anogenital infection with N. gonorrhoeae was documented for about 60% of the patients, and, with one exception, was eradicated by these treatment schedules."} {"id": "PMID:161085", "title": "Effects of hexachlorobutadiene (HCBD) on renal function and renal organic ion transport in the rat.", "content": "1,3-Hexachorobutadiene (HCBD) has been suggested to cause nephrotoxicity. In addition, it is eliminated to a large extent in the urine. This study was designed to examine the effects of HCBD on overall renal function and specific renal transport systems in the rat. A single i.p. dose of 100 mg HCBD/kg caused a reduction in urine osmolality and body weight. Urine flow rate increased slightly and marked increases in urinary protein, glucose and ketones were observed. Renal slices after the same dose showed a reduced PAH accumulation. The transport of other organic compounds was affected only slightly. After daily administration on 4 successive days with various doses a graded response was observed on both transport and overall renal function. Glutathione administered in a 2.5-fold molar excess did not obtund the effects of HCBD on renal function or transport", "contents": "Effects of hexachlorobutadiene (HCBD) on renal function and renal organic ion transport in the rat. 1,3-Hexachorobutadiene (HCBD) has been suggested to cause nephrotoxicity. In addition, it is eliminated to a large extent in the urine. This study was designed to examine the effects of HCBD on overall renal function and specific renal transport systems in the rat. A single i.p. dose of 100 mg HCBD/kg caused a reduction in urine osmolality and body weight. Urine flow rate increased slightly and marked increases in urinary protein, glucose and ketones were observed. Renal slices after the same dose showed a reduced PAH accumulation. The transport of other organic compounds was affected only slightly. After daily administration on 4 successive days with various doses a graded response was observed on both transport and overall renal function. Glutathione administered in a 2.5-fold molar excess did not obtund the effects of HCBD on renal function or transport"} {"id": "PMID:161110", "title": "Occupational exposures to pesticides containing organoarsenicals in California.", "content": "The only organic arsenicals used in agriculture are methanearsonic acid (MSMA) and its sodium and ammonium salts and dimethylarsinic acid (cacodylic acid) and its sodium salt. They have an oral LD50 in the rat of 700-1,000 mg/kg and are classified as toxicity category 3 pesticides. During the three-year period 1975, 1976 and 1977 in California there were 34 reports by physicians of injury due to exposure to pesticides containing organic arsenicals of which nine resulted in systemic symptoms and the remainder being eye and skin irritations. There appeared to be prompt recovery from these exposures. They were caused primarily by use of faulty equipment, not using due care in its operation, poor work practices and improper use of protective equipment. There is no evidence that this group of chemicals is carcinogenic in animals or man.", "contents": "Occupational exposures to pesticides containing organoarsenicals in California. The only organic arsenicals used in agriculture are methanearsonic acid (MSMA) and its sodium and ammonium salts and dimethylarsinic acid (cacodylic acid) and its sodium salt. They have an oral LD50 in the rat of 700-1,000 mg/kg and are classified as toxicity category 3 pesticides. During the three-year period 1975, 1976 and 1977 in California there were 34 reports by physicians of injury due to exposure to pesticides containing organic arsenicals of which nine resulted in systemic symptoms and the remainder being eye and skin irritations. There appeared to be prompt recovery from these exposures. They were caused primarily by use of faulty equipment, not using due care in its operation, poor work practices and improper use of protective equipment. There is no evidence that this group of chemicals is carcinogenic in animals or man."} {"id": "PMID:161116", "title": "[Our experiences with uroflowmetry].", "content": "The uroflowmetry is an essential part of the complex urodynamic examinations. One of its advantages is the non-invasive behaviour; the patient does not suffer any inconveniences. It is suitable for the evaluation of the success in surgical interventions due to obstructions in the lower urinary tracts, for control of results of the medicamentous therapy or after operative procedures, which have as their purpose the improvement of the function of the detrusor and for the general differentiation of diseases which are accompanied by dysuric symptoms. The technique renders possible the registration, the preservation of date and means an unlimited repeatable methody.", "contents": "[Our experiences with uroflowmetry]. The uroflowmetry is an essential part of the complex urodynamic examinations. One of its advantages is the non-invasive behaviour; the patient does not suffer any inconveniences. It is suitable for the evaluation of the success in surgical interventions due to obstructions in the lower urinary tracts, for control of results of the medicamentous therapy or after operative procedures, which have as their purpose the improvement of the function of the detrusor and for the general differentiation of diseases which are accompanied by dysuric symptoms. The technique renders possible the registration, the preservation of date and means an unlimited repeatable methody."} {"id": "PMID:161128", "title": "[Spastic lock of fallopian tube in laparoscopic representation (author's transl)].", "content": "Spastic tubal occlusion was established by laparoscopy, a condition recorded on tubal function tests primarily from patients with genital hypoplasia. These accounted for eight per cent of all patients examined for sterility. Hints are given on the detection of tubal spasm, differential diagnosis for delimitation from organically caused tubal occlusion, and remedial action.", "contents": "[Spastic lock of fallopian tube in laparoscopic representation (author's transl)]. Spastic tubal occlusion was established by laparoscopy, a condition recorded on tubal function tests primarily from patients with genital hypoplasia. These accounted for eight per cent of all patients examined for sterility. Hints are given on the detection of tubal spasm, differential diagnosis for delimitation from organically caused tubal occlusion, and remedial action."} {"id": "PMID:161129", "title": "[Histophysiological characterisation of chorion. Histological, histochemical, and electron-microscopic investigations (author's transl)].", "content": "Histological, histochemical, and electron-microscopic techniques were used to investigate the chorion in 15 women over the first four to eight weeks of normal pregnancy. Evidence was produced to maximum enzyme activity and lipoid accumulation between the sixth and eighth weeks. These findings were confirmed by ultrastructural observation. Data were collected on active exchange in x-cells. That exchange together with manifest delta 5-3-beta hydroxysteroid-dehydrogenase were found to cause not only oxidative processes, but, with some reasonable probability, synthesis of steroid hormones in the chorion, as well.", "contents": "[Histophysiological characterisation of chorion. Histological, histochemical, and electron-microscopic investigations (author's transl)]. Histological, histochemical, and electron-microscopic techniques were used to investigate the chorion in 15 women over the first four to eight weeks of normal pregnancy. Evidence was produced to maximum enzyme activity and lipoid accumulation between the sixth and eighth weeks. These findings were confirmed by ultrastructural observation. Data were collected on active exchange in x-cells. That exchange together with manifest delta 5-3-beta hydroxysteroid-dehydrogenase were found to cause not only oxidative processes, but, with some reasonable probability, synthesis of steroid hormones in the chorion, as well."} {"id": "PMID:161130", "title": "A comparative study of DNA-induced transformants and spontaneous revertants of inositolless Neurospora crassa.", "content": "Inositolless (inl-) Neurospora crassa strains were treated with DNA (allo-DNA) of wild type N. Crassa. Hyphal fragments of a mycelial suspension of the N. Crassa ragged inl- strain used as recipient in our transformation experiments were found to consist of units containing 100--1000 nuclei. In this strain the inositol-independent (inl+) nuclei appearing after DNA treatment or by spontaneous reversion are present in the cytoplasm together with a large number of inl- nuclei. Thus, both transformation and reversion initially must result in heterokaryosis. Under appropriate conditions the inl- nuclei can be detected in the transformed and spontaneous inl+ phenotype revertant strains. Spontaneous revertants are usually characterized by the loss of their inl+ nuclei after transfers on inositol-supplemented medium. On minimal medium, the growth rate of transformed strains is significantly lower than that of spontaneous revertants. The inl+ gene appearing after DNA treatment or by spontaneous reversion is inherited as a trait bound to chromosomes. In crosses with the transformed strains, there is a significant increase in the number of non-Mendelian (6:2 and 5:3) tetrads in the inl locus.", "contents": "A comparative study of DNA-induced transformants and spontaneous revertants of inositolless Neurospora crassa. Inositolless (inl-) Neurospora crassa strains were treated with DNA (allo-DNA) of wild type N. Crassa. Hyphal fragments of a mycelial suspension of the N. Crassa ragged inl- strain used as recipient in our transformation experiments were found to consist of units containing 100--1000 nuclei. In this strain the inositol-independent (inl+) nuclei appearing after DNA treatment or by spontaneous reversion are present in the cytoplasm together with a large number of inl- nuclei. Thus, both transformation and reversion initially must result in heterokaryosis. Under appropriate conditions the inl- nuclei can be detected in the transformed and spontaneous inl+ phenotype revertant strains. Spontaneous revertants are usually characterized by the loss of their inl+ nuclei after transfers on inositol-supplemented medium. On minimal medium, the growth rate of transformed strains is significantly lower than that of spontaneous revertants. The inl+ gene appearing after DNA treatment or by spontaneous reversion is inherited as a trait bound to chromosomes. In crosses with the transformed strains, there is a significant increase in the number of non-Mendelian (6:2 and 5:3) tetrads in the inl locus."} {"id": "PMID:161131", "title": "Kinetic modelling of yeast phosphofructokinase.", "content": "Phosphofructokinase from baker's yeast (Saccharomyces cerevisiae) is an octameric enzyme which exhibits complex allosteric behaviour. In contrast to mammalian phosphofructokinase, the enzyme does not show association-dissociation behaviour. A systematic kinetic investigation at pH 7.2 in dependence on the substrates, fructose 6-phosphate and ATP as well as on the effectors AMP and ADP is presented. The results are interpreted in terms of a structure oriented theoretical model. Because the two state model of Monod, Wyman and Changeux proved to be insufficient for interpretation of the experimental data, it was extended to a four state model in which the basic conformations R and T of the enzyme are split into subconformations R1 and R2 as well as T1 and T2, respectively. It is assumed that fructose 6-phosphate and the adenine nucleotides influence different allosteric equilibria. The model permits a precise quantitative description of the experimental data.", "contents": "Kinetic modelling of yeast phosphofructokinase. Phosphofructokinase from baker's yeast (Saccharomyces cerevisiae) is an octameric enzyme which exhibits complex allosteric behaviour. In contrast to mammalian phosphofructokinase, the enzyme does not show association-dissociation behaviour. A systematic kinetic investigation at pH 7.2 in dependence on the substrates, fructose 6-phosphate and ATP as well as on the effectors AMP and ADP is presented. The results are interpreted in terms of a structure oriented theoretical model. Because the two state model of Monod, Wyman and Changeux proved to be insufficient for interpretation of the experimental data, it was extended to a four state model in which the basic conformations R and T of the enzyme are split into subconformations R1 and R2 as well as T1 and T2, respectively. It is assumed that fructose 6-phosphate and the adenine nucleotides influence different allosteric equilibria. The model permits a precise quantitative description of the experimental data."} {"id": "PMID:161134", "title": "Significance of HLA antigens and the mixed lymphocyte reaction in psoriasis.", "content": "Human Major Histocompatibility (HLA) complex antigens B13, BW16, BW17, CW6 and D-MA are increased in frequency in patients with psoriasis. Of these, the strongest association is with HLA-CW6 and D-MA, with a relative risk of 10.4. Since no strong association with any HLA-A locus antigen is seen, it seems likely that the disease susceptibility gene for psoriasis lies close to the HLA-D locus, which is defined by the use of the mixed lymphocyte reaction (MLR). In the mouse, the Immune response (Ir) genes are found in the MLR region and it is thought that Ia antigens lie at a corresponding location in man. Recently, we have demonstrated that human epidermal cells cause stimulation in the mixed lymphocyte reaction. Lymphocyte antigens which stimulate in this reaction are known to be products of HLA genes and anti-HLA-D sera block stimulation by epidermal cells. It is possible that these antigens may be involved in the regulation of cell--cell communication. Psoriasis is a disease characterized by epidermal hyperproliferation. It is possible, therefore, that an HLA-linked deficiency of recognition between epidermal cells exists in patients with psoriasis and that this defect allows abnormal cellular proliferation to occur.", "contents": "Significance of HLA antigens and the mixed lymphocyte reaction in psoriasis. Human Major Histocompatibility (HLA) complex antigens B13, BW16, BW17, CW6 and D-MA are increased in frequency in patients with psoriasis. Of these, the strongest association is with HLA-CW6 and D-MA, with a relative risk of 10.4. Since no strong association with any HLA-A locus antigen is seen, it seems likely that the disease susceptibility gene for psoriasis lies close to the HLA-D locus, which is defined by the use of the mixed lymphocyte reaction (MLR). In the mouse, the Immune response (Ir) genes are found in the MLR region and it is thought that Ia antigens lie at a corresponding location in man. Recently, we have demonstrated that human epidermal cells cause stimulation in the mixed lymphocyte reaction. Lymphocyte antigens which stimulate in this reaction are known to be products of HLA genes and anti-HLA-D sera block stimulation by epidermal cells. It is possible that these antigens may be involved in the regulation of cell--cell communication. Psoriasis is a disease characterized by epidermal hyperproliferation. It is possible, therefore, that an HLA-linked deficiency of recognition between epidermal cells exists in patients with psoriasis and that this defect allows abnormal cellular proliferation to occur."} {"id": "PMID:161135", "title": "Psoriasis: odd varieties in the adult.", "content": "Occasionally we observe particular varieties of psoriasis and in rare cases transitional features with other diseases, which pose problems concerning the differential diagnosis and the nosological classification. This communication deals with the following clinical and histological aspects of psoriasis: 1) Sebopsoriasis. Relationship of psoriasis to pityriasis rubra pilaris. 2) Erythema annulare centrifugum type of psoriasis. 3) Is subcorneal pustular dermatosis an expression of pustular psoriasis? 4) Salient histopathological criteria for the diagnosis of the different atypical forms of psoriasis. 5) Presentation of an unusal case with striated and retiform verrucous psoriasis-like eruptions, which show a relationship to parakeratosis variegata.", "contents": "Psoriasis: odd varieties in the adult. Occasionally we observe particular varieties of psoriasis and in rare cases transitional features with other diseases, which pose problems concerning the differential diagnosis and the nosological classification. This communication deals with the following clinical and histological aspects of psoriasis: 1) Sebopsoriasis. Relationship of psoriasis to pityriasis rubra pilaris. 2) Erythema annulare centrifugum type of psoriasis. 3) Is subcorneal pustular dermatosis an expression of pustular psoriasis? 4) Salient histopathological criteria for the diagnosis of the different atypical forms of psoriasis. 5) Presentation of an unusal case with striated and retiform verrucous psoriasis-like eruptions, which show a relationship to parakeratosis variegata."} {"id": "PMID:161136", "title": "Particular clinical features of psoriasis in infants and chidren.", "content": "The onset of psoriasis is observed before the age of 10 years in 15% of all patients. The clinical pattern often takes on a peculiar form. Psoriasis guttata--or less frequently nummular psoriasis--is the initial phase during childhood. It is very difficult to establish a diagnosis on the basis of incipient features when childhood psoriasis is located on the head, palms, soles, or on the fingers, toes and nails. Intertriginous or flexural psoriasis, psoriasis spinulosa and oral psoriasis is also described. The onset of napkin psoriasis starts at the age of 3 months. Occasionally, Leiner's disease may develop into a typical, chronic psoriasis. We have concentrated our studies on the less common features of childhood psoriasis: the generalized pustular infantile form, congenital psoriatic erythroderma, acquired psoriatic erythroderma, and infantile arthropathic psoriasis.", "contents": "Particular clinical features of psoriasis in infants and chidren. The onset of psoriasis is observed before the age of 10 years in 15% of all patients. The clinical pattern often takes on a peculiar form. Psoriasis guttata--or less frequently nummular psoriasis--is the initial phase during childhood. It is very difficult to establish a diagnosis on the basis of incipient features when childhood psoriasis is located on the head, palms, soles, or on the fingers, toes and nails. Intertriginous or flexural psoriasis, psoriasis spinulosa and oral psoriasis is also described. The onset of napkin psoriasis starts at the age of 3 months. Occasionally, Leiner's disease may develop into a typical, chronic psoriasis. We have concentrated our studies on the less common features of childhood psoriasis: the generalized pustular infantile form, congenital psoriatic erythroderma, acquired psoriatic erythroderma, and infantile arthropathic psoriasis."} {"id": "PMID:161133", "title": "Surface features and behavior of the connective tissue cell.", "content": "The surface features and behavior of the connective tissue cell in normal areas and in healing incisions of the aponeuroses of the abdominal wall of the albino rat were studied with the scanning electron microscope (SEM). The normal cell is smooth, oval or triangular in outline and has a generally rounded surface and very short or no cell processes. The behavior of the fibroblasts and the condition of the fibers in and around the wounds were visualized. Shortly after the incision, the fibroblasts accumulated around the wound, possibly by increased cell division. At the site of the incision the cells responded by a self-protective mechanism in which they withdrew their processes and acquired a spheroid form. During the maximum period of a fibrillogenesis the fibroblasts enlarged, acquired a fusiform outline and long processes, exhibited a roughened surface and were surrounded with small rounded cell particles polymerizing into fine fibrils. The process of collagen secretion and three stages of collagen maturation were visualized. Some abnormal cells were seen; they could be evidence of merocrine or holocrine mode of secretion or possibly signs of cell senility.", "contents": "Surface features and behavior of the connective tissue cell. The surface features and behavior of the connective tissue cell in normal areas and in healing incisions of the aponeuroses of the abdominal wall of the albino rat were studied with the scanning electron microscope (SEM). The normal cell is smooth, oval or triangular in outline and has a generally rounded surface and very short or no cell processes. The behavior of the fibroblasts and the condition of the fibers in and around the wounds were visualized. Shortly after the incision, the fibroblasts accumulated around the wound, possibly by increased cell division. At the site of the incision the cells responded by a self-protective mechanism in which they withdrew their processes and acquired a spheroid form. During the maximum period of a fibrillogenesis the fibroblasts enlarged, acquired a fusiform outline and long processes, exhibited a roughened surface and were surrounded with small rounded cell particles polymerizing into fine fibrils. The process of collagen secretion and three stages of collagen maturation were visualized. Some abnormal cells were seen; they could be evidence of merocrine or holocrine mode of secretion or possibly signs of cell senility."} {"id": "PMID:161138", "title": "Anticataleptic action of psychostimulating drugs and serotonin in brain.", "content": "The effects of drugs changing serotonin activity in rats were studied observing changes in the anticataleptic action of amphetamine and ephedrine. It was observed that: 1) parachlorophenylalanine prolonged the anticataleptic action of ephedrine and, in part also, that of amphetamine, 2) methysergide alone exerted an anticataleptic effect and enhanced somewhat the same effect of both psychostimulating drugs used, 3) d, 1-tryptophan increased the intensity of catalepsy and reduced very significantly or abolished completely the anticataleptic action of ephedrine and amphetamine. These results support the view that the serotonin system exerts a suppressing effect on the central effects resulting from stimulation of catecholamine dependent functions.", "contents": "Anticataleptic action of psychostimulating drugs and serotonin in brain. The effects of drugs changing serotonin activity in rats were studied observing changes in the anticataleptic action of amphetamine and ephedrine. It was observed that: 1) parachlorophenylalanine prolonged the anticataleptic action of ephedrine and, in part also, that of amphetamine, 2) methysergide alone exerted an anticataleptic effect and enhanced somewhat the same effect of both psychostimulating drugs used, 3) d, 1-tryptophan increased the intensity of catalepsy and reduced very significantly or abolished completely the anticataleptic action of ephedrine and amphetamine. These results support the view that the serotonin system exerts a suppressing effect on the central effects resulting from stimulation of catecholamine dependent functions."} {"id": "PMID:161143", "title": "Hypercapnia and hyperkalaemia.", "content": "Studies in patients undergoing peritoneal laparoscopy, in which carbon dioxide was used as insufflating gas, showed that artificial hyperventilation was an effective means of preventing serious hypercapnia. The hypercapnia caused a rapid hyperkalaemia and there was a linear relationship between the two. Reversal of the hypercapnia caused the serum potassium to fall towards normal but the speed of this fall did not match the speed of reduction in Paco2. It is suggested that the changes in serum potassium following changes in Paco2 may have some clinical relevance in potassium-depicted patients.", "contents": "Hypercapnia and hyperkalaemia. Studies in patients undergoing peritoneal laparoscopy, in which carbon dioxide was used as insufflating gas, showed that artificial hyperventilation was an effective means of preventing serious hypercapnia. The hypercapnia caused a rapid hyperkalaemia and there was a linear relationship between the two. Reversal of the hypercapnia caused the serum potassium to fall towards normal but the speed of this fall did not match the speed of reduction in Paco2. It is suggested that the changes in serum potassium following changes in Paco2 may have some clinical relevance in potassium-depicted patients."} {"id": "PMID:161145", "title": "\"9 + 0\" immotile spermatozoa in an infertile man.", "content": "In this paper the peculiar case of an infertile man, possessing only normally shaped, but stiff and immotile spermatozoa is described. All the sperm are conventionally structured, with the constant characteristic of the absence of central tubules and projections forming the so-called central sheath. Electrophoretic analysis of the high molecular weight polypeptide chains attributed to dyneins shows the constant absence of one chain. The importance of the central structure, usually belonging to the \"9 + 2\" model spermatozoa, and the possible localization of a dynein chain in this region are discussed.", "contents": "\"9 + 0\" immotile spermatozoa in an infertile man. In this paper the peculiar case of an infertile man, possessing only normally shaped, but stiff and immotile spermatozoa is described. All the sperm are conventionally structured, with the constant characteristic of the absence of central tubules and projections forming the so-called central sheath. Electrophoretic analysis of the high molecular weight polypeptide chains attributed to dyneins shows the constant absence of one chain. The importance of the central structure, usually belonging to the \"9 + 2\" model spermatozoa, and the possible localization of a dynein chain in this region are discussed."} {"id": "PMID:161146", "title": "[Neuromuscular block control during and after anaesthesia (author's transl)].", "content": "During many years the clinician's requirements for neuromuscular blocking drugs are satisfied by clinical investigations. Electromyographic recordings which are a satisfactory method are not useful in current practice. The use of nerve stimulators as Churchill Davidson apparatus modified for train of four impulses must reach the continental theatres, the response to neuromuscular blocking agents varying over a wide range. Five ways of stimulation can be used giving different informations, not only during anaesthesia, but so after particularly to specify the origin of some complications.", "contents": "[Neuromuscular block control during and after anaesthesia (author's transl)]. During many years the clinician's requirements for neuromuscular blocking drugs are satisfied by clinical investigations. Electromyographic recordings which are a satisfactory method are not useful in current practice. The use of nerve stimulators as Churchill Davidson apparatus modified for train of four impulses must reach the continental theatres, the response to neuromuscular blocking agents varying over a wide range. Five ways of stimulation can be used giving different informations, not only during anaesthesia, but so after particularly to specify the origin of some complications."} {"id": "PMID:161147", "title": "[Acute rheumatic carditis. Follow-up (author's transl)].", "content": "Thirteen cases with a first attack of acute theumatic carditis are presented, analyzing the clinical picture and long-term follow-up. Although the clinical acute attack was quite benign, incidence and importance of residual heart disease has not changed.", "contents": "[Acute rheumatic carditis. Follow-up (author's transl)]. Thirteen cases with a first attack of acute theumatic carditis are presented, analyzing the clinical picture and long-term follow-up. Although the clinical acute attack was quite benign, incidence and importance of residual heart disease has not changed."} {"id": "PMID:161152", "title": "Comparison of the plaque-stimulating and thymocyte-stimulating activities derived from human monocytes.", "content": "Human monocytes have been reported to release factors that can elicit distinct responses from a number of different target cells. In this report, it is shown that most of the thymocyte-stimulating activity in supernatants of endotoxin-stimulated monocytes can be separated from the plaque-stimulating factor (BAF) by gel filtration and isoelectric focusing; however, since these activities could not be entirely resolved, the question was addressed whether the plaque-stimulating activity of BAF depends upon the stimulation of T-cells. Several critical experiments are reported which fail to support this hypothesis. On the other hand, these experiments led to the observation that the response to BAF depends on both an IgM-positive B-cell and a G10-adherent, plastic nonadherent, IgM-negative, irradiation-insensitive cell found in nude splenocytes. Finally, the possibility is discussed that this factor may be responsible for many of the physiological sequelae of infection.", "contents": "Comparison of the plaque-stimulating and thymocyte-stimulating activities derived from human monocytes. Human monocytes have been reported to release factors that can elicit distinct responses from a number of different target cells. In this report, it is shown that most of the thymocyte-stimulating activity in supernatants of endotoxin-stimulated monocytes can be separated from the plaque-stimulating factor (BAF) by gel filtration and isoelectric focusing; however, since these activities could not be entirely resolved, the question was addressed whether the plaque-stimulating activity of BAF depends upon the stimulation of T-cells. Several critical experiments are reported which fail to support this hypothesis. On the other hand, these experiments led to the observation that the response to BAF depends on both an IgM-positive B-cell and a G10-adherent, plastic nonadherent, IgM-negative, irradiation-insensitive cell found in nude splenocytes. Finally, the possibility is discussed that this factor may be responsible for many of the physiological sequelae of infection."} {"id": "PMID:161154", "title": "Thymosin modulation of suppressor function in mice and man.", "content": "The effect of thymosin on suppressor-cell function was evaluated in vivo in a murine tumor system and in vitro on human lymphocytes. In mice, the Lewis tumor system was used. We showed that splenocytes from tumor-bearing animals were able to enhance tumor growth in a syngeneic system. This enhancement was similar when thymocytes from tumor-bearing animals were used and disappeared after anti-Thy 1-2 antiserum treatment, suggesting a T-dependence. Treatment of the tumor-growth-enhancing lymphocytes with corticosteroids or irradiation caused this effect to disappear completely suggesting that the tumor-growth-enhancing T-lymphocytes were suppressor T-cells. Furthermore thymosin (fraction 5)-treated, tumor-growth-enhancing T-lymphocytes were not able to enhance tumor growth and even significantly decreased it. In the human system we showed that Con A-stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM, and Con A, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.", "contents": "Thymosin modulation of suppressor function in mice and man. The effect of thymosin on suppressor-cell function was evaluated in vivo in a murine tumor system and in vitro on human lymphocytes. In mice, the Lewis tumor system was used. We showed that splenocytes from tumor-bearing animals were able to enhance tumor growth in a syngeneic system. This enhancement was similar when thymocytes from tumor-bearing animals were used and disappeared after anti-Thy 1-2 antiserum treatment, suggesting a T-dependence. Treatment of the tumor-growth-enhancing lymphocytes with corticosteroids or irradiation caused this effect to disappear completely suggesting that the tumor-growth-enhancing T-lymphocytes were suppressor T-cells. Furthermore thymosin (fraction 5)-treated, tumor-growth-enhancing T-lymphocytes were not able to enhance tumor growth and even significantly decreased it. In the human system we showed that Con A-stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM, and Con A, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5."} {"id": "PMID:161156", "title": "Phosphorylation of streptozotocin during uptake via the phosphoenolpyruvate: sugar phosphotransferase system in Escherichia coli.", "content": "Mutants of Escherichia coli K-12, Staphylococcus aureus, and Bacillus subtilis defective in the general components (enzyme I, or HPr, or both) of the phosphoenolpyruvate:sugar phosphotransferase system are shown to be resistant to the antibiotic streptozotocin. It is shown here, employing 32P-labeled phosphoenolpyruvate, that wild-type cells of E. coli phosphorylate streptozotocin, whereas with a phosphotransferase system-defective mutant of E. coli the drug is recovered in an unaltered, free form. The internal accumulation of streptozotocin at the steady-state level was about 70 times that of the concentration in the external medium. The antibacterial action of streptozotocin, as well as the uptake of the drug, was inhibited by N-acetyl-D-glucosamine. The uptake of the antibiotic was extremely sensitive to p-chloromercuribenzoate. It is concluded that streptozotocin is taken up by E. coli via the phosphoenolpyruvate:sugar phosphotransferase system and consequently accumulates in the cell at first as streptozotocin-phosphate.", "contents": "Phosphorylation of streptozotocin during uptake via the phosphoenolpyruvate: sugar phosphotransferase system in Escherichia coli. Mutants of Escherichia coli K-12, Staphylococcus aureus, and Bacillus subtilis defective in the general components (enzyme I, or HPr, or both) of the phosphoenolpyruvate:sugar phosphotransferase system are shown to be resistant to the antibiotic streptozotocin. It is shown here, employing 32P-labeled phosphoenolpyruvate, that wild-type cells of E. coli phosphorylate streptozotocin, whereas with a phosphotransferase system-defective mutant of E. coli the drug is recovered in an unaltered, free form. The internal accumulation of streptozotocin at the steady-state level was about 70 times that of the concentration in the external medium. The antibacterial action of streptozotocin, as well as the uptake of the drug, was inhibited by N-acetyl-D-glucosamine. The uptake of the antibiotic was extremely sensitive to p-chloromercuribenzoate. It is concluded that streptozotocin is taken up by E. coli via the phosphoenolpyruvate:sugar phosphotransferase system and consequently accumulates in the cell at first as streptozotocin-phosphate."} {"id": "PMID:161157", "title": "Zearalenone, deoxynivalenol, and T-2 toxin associated with stalk rot in corn.", "content": "The mycotoxins zearalenone (2.8 micrograms/g), deoxynivalenol (1.5 microgram/g), and T-2 toxin (110 ng/g) have been found in the pith of corn stalks standing in the field. Such contaminated stalks may contribute to mycotoxicoses of farm animals.", "contents": "Zearalenone, deoxynivalenol, and T-2 toxin associated with stalk rot in corn. The mycotoxins zearalenone (2.8 micrograms/g), deoxynivalenol (1.5 microgram/g), and T-2 toxin (110 ng/g) have been found in the pith of corn stalks standing in the field. Such contaminated stalks may contribute to mycotoxicoses of farm animals."} {"id": "PMID:161159", "title": "Mouse epidermal and skin extracts tested for cytostatic activity (\"chalones\"). Effects on organ and cell cultures.", "content": "Crude and fractionated epidermal extracts have been shown to decrease the growth and viability of epidermal cells (mouse ear organ cultures) as well as of murine mastocytoma cells, fibroblasts (L cells) and kidney cells (primary cultures). This cytotoxicity has been demonstrated to be due to the extracts and not to parasitic toxins. Furthermore, extracts prepared from dermis, mammary glands, and liver were likewise cytotoxic. These results do not confirm the presence of tissue-specific growth inhibitors (chalones) which have been claimed by others to be present in epidermal extracts.", "contents": "Mouse epidermal and skin extracts tested for cytostatic activity (\"chalones\"). Effects on organ and cell cultures. Crude and fractionated epidermal extracts have been shown to decrease the growth and viability of epidermal cells (mouse ear organ cultures) as well as of murine mastocytoma cells, fibroblasts (L cells) and kidney cells (primary cultures). This cytotoxicity has been demonstrated to be due to the extracts and not to parasitic toxins. Furthermore, extracts prepared from dermis, mammary glands, and liver were likewise cytotoxic. These results do not confirm the presence of tissue-specific growth inhibitors (chalones) which have been claimed by others to be present in epidermal extracts."} {"id": "PMID:161160", "title": "Gonococcal urethritis--diagnosis and treatment.", "content": "For men with urethral discharge, a simple gram stained smear is 98% sensitive and over 99% specific in detecting gonococcal infection when compared to a single Thayer-Martin culture. The smear is less than 50% sensitive in asymptomatic urethritis. Neither Fluorescent antibody nor various serologic tests offer any diagnostic advantages over smears and/or cultures and they are not cost-effective. Treatment of gonococcal urethritis may be successfully accomplished with a variety of antibiotic regimens. Tetracycline hydrochloride (500 mg four times a day for 5 days) is highly effective, inexpensive, and is active against Chlamydia trachomatis; post gonococcal urethritis (PGU) is therefore uncommon. Aqueous Procaine Penicillin G (4.8 million units IM with 1 g of probenecid) has become the standard in the United States but suffers from higher cost, the need for refrigeration, occasional alarming toxic procaine reactions, and a high incidence of PGU. Spectinomycin 2 g IM remains expensive but is the regimen of choice for treatment failures and for Neisseria gonorrhoeae that produce penicillinase (PPNG). Other antibiotics active against PPNG are cotrimoxozole, cefoxitin, and cefuroxime. PNNG have now been reported from 27 countries throughout the world, but have attained significant prevalence in only a few areas of East Asia and West Africa. Because gonococcal patterns of antibiotic resistance are constantly changing, each region of the world needs to monitor treatment results and maintain some surveillance over sensitivity to antibiotics.", "contents": "Gonococcal urethritis--diagnosis and treatment. For men with urethral discharge, a simple gram stained smear is 98% sensitive and over 99% specific in detecting gonococcal infection when compared to a single Thayer-Martin culture. The smear is less than 50% sensitive in asymptomatic urethritis. Neither Fluorescent antibody nor various serologic tests offer any diagnostic advantages over smears and/or cultures and they are not cost-effective. Treatment of gonococcal urethritis may be successfully accomplished with a variety of antibiotic regimens. Tetracycline hydrochloride (500 mg four times a day for 5 days) is highly effective, inexpensive, and is active against Chlamydia trachomatis; post gonococcal urethritis (PGU) is therefore uncommon. Aqueous Procaine Penicillin G (4.8 million units IM with 1 g of probenecid) has become the standard in the United States but suffers from higher cost, the need for refrigeration, occasional alarming toxic procaine reactions, and a high incidence of PGU. Spectinomycin 2 g IM remains expensive but is the regimen of choice for treatment failures and for Neisseria gonorrhoeae that produce penicillinase (PPNG). Other antibiotics active against PPNG are cotrimoxozole, cefoxitin, and cefuroxime. PNNG have now been reported from 27 countries throughout the world, but have attained significant prevalence in only a few areas of East Asia and West Africa. Because gonococcal patterns of antibiotic resistance are constantly changing, each region of the world needs to monitor treatment results and maintain some surveillance over sensitivity to antibiotics."} {"id": "PMID:161162", "title": "[Mucolipidosis type II. Report of 2 suggestive cases].", "content": "The clinical and laboratorial study of two brothers with gargoylism is reported. The examination of the urine showed normal findings of mucopolysaccharides. The authors made differential diagnoses with others mucolipidoses and concluded that mucolipidose type II should be considered in any patient with gargoylism.", "contents": "[Mucolipidosis type II. Report of 2 suggestive cases]. The clinical and laboratorial study of two brothers with gargoylism is reported. The examination of the urine showed normal findings of mucopolysaccharides. The authors made differential diagnoses with others mucolipidoses and concluded that mucolipidose type II should be considered in any patient with gargoylism."} {"id": "PMID:161163", "title": "[Anatomo-pathological study of the brain in idiopathic cardiomegaly].", "content": "The pathological findings in the brain of patients who died with idiopathic cardiomegaly are reported. The major findings in the 38 studied cases were cerebral infarcts (10,5%) and cerebral atrophy (7,9%) besides the nonspecific histological changes represented by neuronal ischemic alteration, satellitosis of nerve cells and swollen and hyperplasia of endothelial cells in capilaries of the cerebral cortex. These findings were considered a consequence of the venous stasis of the congestive heart failure. These data were compared to those seen in the brain of patients with heart failure in the course of chronic Chagas disease. The morphological findings were similar. The frequence of infarcts and atrophy was higher in the cases of Chagas disease and the cerebral atrophy was seen in an younger group of patients compared to the cases of idiopathic cardiomegaly. It seems that there is another factor also responsible for the occurrence of cerebral atrophy in Chagas disease, since from the clinical and hemodynamic point of view both cardiopathies have many similarities.", "contents": "[Anatomo-pathological study of the brain in idiopathic cardiomegaly]. The pathological findings in the brain of patients who died with idiopathic cardiomegaly are reported. The major findings in the 38 studied cases were cerebral infarcts (10,5%) and cerebral atrophy (7,9%) besides the nonspecific histological changes represented by neuronal ischemic alteration, satellitosis of nerve cells and swollen and hyperplasia of endothelial cells in capilaries of the cerebral cortex. These findings were considered a consequence of the venous stasis of the congestive heart failure. These data were compared to those seen in the brain of patients with heart failure in the course of chronic Chagas disease. The morphological findings were similar. The frequence of infarcts and atrophy was higher in the cases of Chagas disease and the cerebral atrophy was seen in an younger group of patients compared to the cases of idiopathic cardiomegaly. It seems that there is another factor also responsible for the occurrence of cerebral atrophy in Chagas disease, since from the clinical and hemodynamic point of view both cardiopathies have many similarities."} {"id": "PMID:161164", "title": "The current status of home total parenteral nutrition.", "content": "The history and current status of home total parenteral nutrition are reviewed. Patients without a functional intestinal tract are able to lead a relatively normal life, infusing their essential nutrients through a Silastic central venous catheter while they sleep at night. The average catheter life is nine months. Suspected sepsis and obstruction of the catheter were the leading causes for catheter removal.", "contents": "The current status of home total parenteral nutrition. The history and current status of home total parenteral nutrition are reviewed. Patients without a functional intestinal tract are able to lead a relatively normal life, infusing their essential nutrients through a Silastic central venous catheter while they sleep at night. The average catheter life is nine months. Suspected sepsis and obstruction of the catheter were the leading causes for catheter removal."} {"id": "PMID:161166", "title": "Preparation of parietal peritoneum for measurements of in vitro permeability.", "content": "An experimental method for in vitro studies of permeability of parietal peritoneal membrane was developed in rats. Sodium and potassium fluxes across the peritoneum lining two different regions (the diaphragm and the anterior abdominal wall) were estimated and electrical resistance of the isolated membranes were determined. A significant reciprocal correlation was observed between the two indices. Quantitative differences between the two types of membranes were found, the diaphragmatic region being more permeable than the other. It is suggested that a monolayer of mesothelial cells covering the membranes is partially responsible for these differences. The parietal peritoneum was found to be less permeable than visceral peritoneum (mesentery) studied under identical conditions.", "contents": "Preparation of parietal peritoneum for measurements of in vitro permeability. An experimental method for in vitro studies of permeability of parietal peritoneal membrane was developed in rats. Sodium and potassium fluxes across the peritoneum lining two different regions (the diaphragm and the anterior abdominal wall) were estimated and electrical resistance of the isolated membranes were determined. A significant reciprocal correlation was observed between the two indices. Quantitative differences between the two types of membranes were found, the diaphragmatic region being more permeable than the other. It is suggested that a monolayer of mesothelial cells covering the membranes is partially responsible for these differences. The parietal peritoneum was found to be less permeable than visceral peritoneum (mesentery) studied under identical conditions."} {"id": "PMID:161161", "title": "[Congenital adrenal hyperplasia due to blockade of 3-beta-hydroxysteroid dehydrogenase].", "content": "Five cases of congenital 3 beta-hydroxysteroid deshydrogenase deficiency in children are reported: four boys with perineal posterior hypospadias and one girl with clitoromegaly. The salt losing syndrome was clinically overt in only three patients. The main biological character was the very high level of plasma dehydroepiandrosterone (DHA) with an elevated DHA/delta 4 androstenedione ratio. The 17 alpha-OH progesterone, though in normal biosynthesis of glucocorticoids being produced beyond the enzymatic block, was raised, but this apparently paradoxical observation may assist making the diagnosis. Deficient production of testosterone was demonstrated in the prepubertal boys by absence of postnatal rise in plasma testosterone or a decreased reponse of plasma testosterone to chorionic gonadotrophin. It is concluded that deficiency of 3 beta-hydroxysteroid deshydrogenase, now easily recognizable with the use of plasma steroids radioimmunoassay, is probably less rare than was apparent with the use of urinary steroid estimations.", "contents": "[Congenital adrenal hyperplasia due to blockade of 3-beta-hydroxysteroid dehydrogenase]. Five cases of congenital 3 beta-hydroxysteroid deshydrogenase deficiency in children are reported: four boys with perineal posterior hypospadias and one girl with clitoromegaly. The salt losing syndrome was clinically overt in only three patients. The main biological character was the very high level of plasma dehydroepiandrosterone (DHA) with an elevated DHA/delta 4 androstenedione ratio. The 17 alpha-OH progesterone, though in normal biosynthesis of glucocorticoids being produced beyond the enzymatic block, was raised, but this apparently paradoxical observation may assist making the diagnosis. Deficient production of testosterone was demonstrated in the prepubertal boys by absence of postnatal rise in plasma testosterone or a decreased reponse of plasma testosterone to chorionic gonadotrophin. It is concluded that deficiency of 3 beta-hydroxysteroid deshydrogenase, now easily recognizable with the use of plasma steroids radioimmunoassay, is probably less rare than was apparent with the use of urinary steroid estimations."} {"id": "PMID:161167", "title": "Determination of cardiac output of the artificial heart from the drive air flow.", "content": "An indication chamber, inserted between the right heart drive and the pump proper, was designed to provide continual measurement of the quantity of blood pumped by the pneumatic artificial heart. The flow is evaluated from the motion of a piston provided with a photoelectric transducer. The effect of compressibility of the drive gas on measurement accuracy is eliminated. The indication chamber provides for automatic replenishment of gas that escapes by diffusion and through minor leakage. During testing in an artificial circulation within the range of physiological conditions, measurement in accuracies did not exceed 5%.", "contents": "Determination of cardiac output of the artificial heart from the drive air flow. An indication chamber, inserted between the right heart drive and the pump proper, was designed to provide continual measurement of the quantity of blood pumped by the pneumatic artificial heart. The flow is evaluated from the motion of a piston provided with a photoelectric transducer. The effect of compressibility of the drive gas on measurement accuracy is eliminated. The indication chamber provides for automatic replenishment of gas that escapes by diffusion and through minor leakage. During testing in an artificial circulation within the range of physiological conditions, measurement in accuracies did not exceed 5%."} {"id": "PMID:161168", "title": "Genetic counselling for neurological disorders.", "content": "When parents have a child with any problem, they usually become concerned about the chances of this problem recurring if they have further children, or of appearing in their grandchildren. Similarly, persons with any congenital disorder themselves or family history of such disorder, often worry about their future children. Genetic counselling can in most cases provide reassurance that there is little need for concern. In those instances where the risks are real, they can be put into perspective and often effectively circumvented by procedures such as prenatal diagnosis. Pregnant women of advanced age run increased risks of having children with chromosome disorders; it is of benefit to individual couples and to the community to refer such women for amniocentesis.", "contents": "Genetic counselling for neurological disorders. When parents have a child with any problem, they usually become concerned about the chances of this problem recurring if they have further children, or of appearing in their grandchildren. Similarly, persons with any congenital disorder themselves or family history of such disorder, often worry about their future children. Genetic counselling can in most cases provide reassurance that there is little need for concern. In those instances where the risks are real, they can be put into perspective and often effectively circumvented by procedures such as prenatal diagnosis. Pregnant women of advanced age run increased risks of having children with chromosome disorders; it is of benefit to individual couples and to the community to refer such women for amniocentesis."} {"id": "PMID:161169", "title": "'Oscopy' in obstetrics and gynaecology.", "content": "Endoscopy has enhanced the science and practice of obstetrics and gynaecology immeasurably over the last decade. There is an established place for most of these procedures, especially in the case of laparoscopy. The hazard of laparoscopy should be able to be further reduced. In the case of laparoscopic sterilization, probably the most conservative method should be used, especially in those at risk of seeking reversal. Hysteroscopy has a small but significant place, mainly in diagnosis. Although promising, foetoscopy is still very much in the development phase.", "contents": "'Oscopy' in obstetrics and gynaecology. Endoscopy has enhanced the science and practice of obstetrics and gynaecology immeasurably over the last decade. There is an established place for most of these procedures, especially in the case of laparoscopy. The hazard of laparoscopy should be able to be further reduced. In the case of laparoscopic sterilization, probably the most conservative method should be used, especially in those at risk of seeking reversal. Hysteroscopy has a small but significant place, mainly in diagnosis. Although promising, foetoscopy is still very much in the development phase."} {"id": "PMID:161170", "title": "Combined cholinergic antagonist and beta 2-adrenoceptor agonist bronchodilator therapy by inhalation.", "content": "The bronchodilator effects of 40 microgram ipratropium bromide (I) and 400 microgram fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double-blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side-effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma.", "contents": "Combined cholinergic antagonist and beta 2-adrenoceptor agonist bronchodilator therapy by inhalation. The bronchodilator effects of 40 microgram ipratropium bromide (I) and 400 microgram fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double-blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side-effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma."} {"id": "PMID:161173", "title": "Studies on poison ivy. In vitro lymphocyte transformation by urushiol-protein conjugates.", "content": "The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy.", "contents": "Studies on poison ivy. In vitro lymphocyte transformation by urushiol-protein conjugates. The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy."} {"id": "PMID:161174", "title": "Complement C3 and immunoglobulin in inflammatory acne vulgaris.", "content": "In patients with moderate to severe inflammatory acne, complement (C3) was detected by immunofluorescence in sixteen early inflammatory acne lesions but in only one of thirteen biopsies of non-inflamed skin from acne sites. C3 deposition occurred particularly in the walls of small dermal blood vessels and at the dermo-epidermal junction. IgM was identified in vessel walls in four of sixteen early lesions. In eight late inflammatory lesions C3 deposition was much less prominent and was present in vessel walls in only two. None of the late lesions showed vascular deposition of IgM. The observations indicate that complement activation occurs in inflammatory acne and it is suggested that this may play a pathogenic role in the inflammation.", "contents": "Complement C3 and immunoglobulin in inflammatory acne vulgaris. In patients with moderate to severe inflammatory acne, complement (C3) was detected by immunofluorescence in sixteen early inflammatory acne lesions but in only one of thirteen biopsies of non-inflamed skin from acne sites. C3 deposition occurred particularly in the walls of small dermal blood vessels and at the dermo-epidermal junction. IgM was identified in vessel walls in four of sixteen early lesions. In eight late inflammatory lesions C3 deposition was much less prominent and was present in vessel walls in only two. None of the late lesions showed vascular deposition of IgM. The observations indicate that complement activation occurs in inflammatory acne and it is suggested that this may play a pathogenic role in the inflammation."} {"id": "PMID:161175", "title": "The fate of phage lambda DNA in lambda-infected minicells.", "content": "The fate of phage lambda DNA in lambda-infected Escherichia coli minicells harboring the plasmid ColE1, and in plasmid-free minicells, were studied. Binding of lambda DNA to the minicell membrane, and formation of the supercoiled covalently-closed circular structure has been demonstrated. Phage infection abolishes plasmid DNA synthesis. Only a very slight, non-replicative lambda DNA synthesis occurs, soon after infection. This synthesis is associated with fragments of lambda DNA arising during, or soon after its penetration.", "contents": "The fate of phage lambda DNA in lambda-infected minicells. The fate of phage lambda DNA in lambda-infected Escherichia coli minicells harboring the plasmid ColE1, and in plasmid-free minicells, were studied. Binding of lambda DNA to the minicell membrane, and formation of the supercoiled covalently-closed circular structure has been demonstrated. Phage infection abolishes plasmid DNA synthesis. Only a very slight, non-replicative lambda DNA synthesis occurs, soon after infection. This synthesis is associated with fragments of lambda DNA arising during, or soon after its penetration."} {"id": "PMID:161176", "title": "Effect of crosslinking by glutaraldehyde on interaction of F-actin with heavy meromyosin.", "content": "Crosslinking of F-actin by a bifunctional reagent glutaraldehyde resulted in a marked decrease of viscosity and length of F-actin filaments. The extent and rate of superprecipitation of actomyosin reconstituted from the modified actin were lower than those of unmodified actin-myosin complex, but activation of heavy meromyosin ATPase by the crosslinked actin was higher than by unmodified one. Heavy meromyosin ATPase activated by the crosslinked actin was distinctly less dependent on KCl concentration than that activated by unmodified actin. Turbidity of the modified acto-heavy meromyosin in the presence of ATP exceeded the sum of turbidities of actin and heavy meromyosin, whereas in the case of unmodified acto-heavy meromyosin the turbidity was comparable to that for noninteracting system. The difference in activation of heavy meromyosin. ATPase by the cross-linked and unmodified actin, clearly seen at room temperature, significantly diminished when temperature was lowered to 0 degrees C.", "contents": "Effect of crosslinking by glutaraldehyde on interaction of F-actin with heavy meromyosin. Crosslinking of F-actin by a bifunctional reagent glutaraldehyde resulted in a marked decrease of viscosity and length of F-actin filaments. The extent and rate of superprecipitation of actomyosin reconstituted from the modified actin were lower than those of unmodified actin-myosin complex, but activation of heavy meromyosin ATPase by the crosslinked actin was higher than by unmodified one. Heavy meromyosin ATPase activated by the crosslinked actin was distinctly less dependent on KCl concentration than that activated by unmodified actin. Turbidity of the modified acto-heavy meromyosin in the presence of ATP exceeded the sum of turbidities of actin and heavy meromyosin, whereas in the case of unmodified acto-heavy meromyosin the turbidity was comparable to that for noninteracting system. The difference in activation of heavy meromyosin. ATPase by the cross-linked and unmodified actin, clearly seen at room temperature, significantly diminished when temperature was lowered to 0 degrees C."} {"id": "PMID:161178", "title": "General mechanisms of inflammation in rheumatoid arthritis.", "content": "Rheumatoid synovitis is characterized by the simultaneous occurrence of two major types of immunologically-induced inflammation. These usually occur concurrently in the same joint. A cellular immune response is present in the sublining layer of the synovial membrane and an immune complex-induced acute inflammatory reaction is present in the synovial effusion phase of the disease. The two reactions are closely related and mutually interdependent. The cellular immune response is reduced in rheumatoid arthritis, but the chronic inflammatory cells of the synovium are active in the synthesis of IgG and probably considerable amounts of IgG rheumatoid factor. Rheumatoid factor complexes, particularly IgG-RF complexes, appear to be responsible for the exudative, immune complex-induced inflammatory phase of the disease.", "contents": "General mechanisms of inflammation in rheumatoid arthritis. Rheumatoid synovitis is characterized by the simultaneous occurrence of two major types of immunologically-induced inflammation. These usually occur concurrently in the same joint. A cellular immune response is present in the sublining layer of the synovial membrane and an immune complex-induced acute inflammatory reaction is present in the synovial effusion phase of the disease. The two reactions are closely related and mutually interdependent. The cellular immune response is reduced in rheumatoid arthritis, but the chronic inflammatory cells of the synovium are active in the synthesis of IgG and probably considerable amounts of IgG rheumatoid factor. Rheumatoid factor complexes, particularly IgG-RF complexes, appear to be responsible for the exudative, immune complex-induced inflammatory phase of the disease."} {"id": "PMID:161179", "title": "[Bactericidal effects of macrophages of mice treated with interferon].", "content": "The preparations of interferon or virus-inhibiting factor produced in L cell (L-IF) and mouse brain (MB-IF) enhanced the killing of Staphylococcus aureus (S.a.) by the mouse peritoneal macrophage. The L-IF, heat-inactivated at 80 degrees or 60 degrees for 30 min., and mock L-IF could not enhance the killing of S.a. The heterologous human and rabbit interferon preparations didn't enhance the bactericidal activity of macrophage. The L-IF didn't have any effect on the release of lysozyme from the macrophages.", "contents": "[Bactericidal effects of macrophages of mice treated with interferon]. The preparations of interferon or virus-inhibiting factor produced in L cell (L-IF) and mouse brain (MB-IF) enhanced the killing of Staphylococcus aureus (S.a.) by the mouse peritoneal macrophage. The L-IF, heat-inactivated at 80 degrees or 60 degrees for 30 min., and mock L-IF could not enhance the killing of S.a. The heterologous human and rabbit interferon preparations didn't enhance the bactericidal activity of macrophage. The L-IF didn't have any effect on the release of lysozyme from the macrophages."} {"id": "PMID:161180", "title": "[Effect of interferon on the increased reduction of nitroblue tetrazolium (NBT)].", "content": "Human leukocyte interferon (HL-IF) enhanced the NBT reduction of human peripheral neutrophil in vitro. Dose relation between IF activity and the NBT reduction was recognized. Heat-inactivated HL-IF, HL-IF neutralized by anti-IF serum or heterologous IF could not increase the NBT reduction.", "contents": "[Effect of interferon on the increased reduction of nitroblue tetrazolium (NBT)]. Human leukocyte interferon (HL-IF) enhanced the NBT reduction of human peripheral neutrophil in vitro. Dose relation between IF activity and the NBT reduction was recognized. Heat-inactivated HL-IF, HL-IF neutralized by anti-IF serum or heterologous IF could not increase the NBT reduction."} {"id": "PMID:161181", "title": "[Intrahepatic pancrease in Sparus datnia (Ham. Buch.), a Sparidae of the Persian Gulf].", "content": "A fish, Sparus datnia (Ham. Buch.), Sparidae, protandric, is one of the species, which has a diffusing intrahepatic pancreas. The gland is compound of two parts : the exocrine part (follow the branches of the portal vein), and the endocrine part (langerhans islets, more or less abundent in the external side of the endocrine part). Three kinds of granular cells are recognized in the endocrine islets.", "contents": "[Intrahepatic pancrease in Sparus datnia (Ham. Buch.), a Sparidae of the Persian Gulf]. A fish, Sparus datnia (Ham. Buch.), Sparidae, protandric, is one of the species, which has a diffusing intrahepatic pancreas. The gland is compound of two parts : the exocrine part (follow the branches of the portal vein), and the endocrine part (langerhans islets, more or less abundent in the external side of the endocrine part). Three kinds of granular cells are recognized in the endocrine islets."} {"id": "PMID:161182", "title": "[Effects of water intake on variations of plasma renin activity (PRA) and blood aldosterone during physical exercise in man].", "content": "In man, increase of renin and aldosterone levels in sera resulting from a brief and heavy muscular exercise on bicyle ergometer is notably reduced but not abolished by massive hydration.", "contents": "[Effects of water intake on variations of plasma renin activity (PRA) and blood aldosterone during physical exercise in man]. In man, increase of renin and aldosterone levels in sera resulting from a brief and heavy muscular exercise on bicyle ergometer is notably reduced but not abolished by massive hydration."} {"id": "PMID:161183", "title": "[Transfer of monovalent cations across the isolated human amniotic membrane].", "content": "When the conductance and the bi-ionic potential are measured in vitro, monovalent cations are transferred according to a simple diffusion mechanism across the amnion (from the inside to the outside of the amniotic cavity or in the reverse direction) in channels with neutral or negative fixed sites. For equal concentration, the permeability to K+ is superior to that of Na+.", "contents": "[Transfer of monovalent cations across the isolated human amniotic membrane]. When the conductance and the bi-ionic potential are measured in vitro, monovalent cations are transferred according to a simple diffusion mechanism across the amnion (from the inside to the outside of the amniotic cavity or in the reverse direction) in channels with neutral or negative fixed sites. For equal concentration, the permeability to K+ is superior to that of Na+."} {"id": "PMID:161184", "title": "[C-cell hyperplasia in the thyroid of the normal rat].", "content": "During life of normal rat, it appears an hyperplasia of thyro\u00efdeal C cells, eventually till tumors, a progressive hypertrophy of parathyro\u00efd glands and a fall of calcemia. Chronological study of these phenomena shows that C cells hyperplasia precedes parathyro\u00efd hypertrophy. This last so appears as a reaction against hypocalcemia provoked by hyperplasia of parafollicular cells.", "contents": "[C-cell hyperplasia in the thyroid of the normal rat]. During life of normal rat, it appears an hyperplasia of thyro\u00efdeal C cells, eventually till tumors, a progressive hypertrophy of parathyro\u00efd glands and a fall of calcemia. Chronological study of these phenomena shows that C cells hyperplasia precedes parathyro\u00efd hypertrophy. This last so appears as a reaction against hypocalcemia provoked by hyperplasia of parafollicular cells."} {"id": "PMID:161185", "title": "[Effect of the time of theophylline administration on the intensity of diuresis and natriuresis in the rat].", "content": "The present study originates in two experimental data: circadian variations evidence of water, electrolytes and solutes urinary excretion and theophylline diuretic and salidiuretic effects knowledge; we purpose to evidence theophylline-induced water and sodium renal excretion in rats as modified by the time of drug administration. Theophylline single dose is injected in 100 animals (20 lots of 5 rats) at 8 h, 14 h, 20 h or 2 h and urines are collected during a consecutive to injection hours long period: 8 h-14 h (I), 14 h-20 h (II), 20 h-2 h (III) or 2 h-8 h (IV). Diuresis increases in + 40,4 p. cent (I), in + 123,7 p. cent (II), in + 123,3 p. cent (III) in + 65,4 p. cent (IV). So, natriuresis increases in 39,6 p. cent (I), in 223,2 p. cent (II), in 114,3 p cent (III) and in 109,6 p. cent (IV). These results evidence that theophylline diuretic and natriuretic effects change strongly with injection time, being largest if it is injected at 14 h and slightest if injected at 8 h. Such observations prompt to study if the other pharmacological properties of theophylline, especially at pulmonary level, response also with a time-dependant intensity.", "contents": "[Effect of the time of theophylline administration on the intensity of diuresis and natriuresis in the rat]. The present study originates in two experimental data: circadian variations evidence of water, electrolytes and solutes urinary excretion and theophylline diuretic and salidiuretic effects knowledge; we purpose to evidence theophylline-induced water and sodium renal excretion in rats as modified by the time of drug administration. Theophylline single dose is injected in 100 animals (20 lots of 5 rats) at 8 h, 14 h, 20 h or 2 h and urines are collected during a consecutive to injection hours long period: 8 h-14 h (I), 14 h-20 h (II), 20 h-2 h (III) or 2 h-8 h (IV). Diuresis increases in + 40,4 p. cent (I), in + 123,7 p. cent (II), in + 123,3 p. cent (III) in + 65,4 p. cent (IV). So, natriuresis increases in 39,6 p. cent (I), in 223,2 p. cent (II), in 114,3 p cent (III) and in 109,6 p. cent (IV). These results evidence that theophylline diuretic and natriuretic effects change strongly with injection time, being largest if it is injected at 14 h and slightest if injected at 8 h. Such observations prompt to study if the other pharmacological properties of theophylline, especially at pulmonary level, response also with a time-dependant intensity."} {"id": "PMID:161186", "title": "[Demonstration of the myotoxic effect of theophylline on the isolated kidney glomerulus of the rat].", "content": "After confirmation of the intense and very fast myorelaxant effect of theophylline on isolated glomeruli, xanthic reagent myotoxic effects are shown during more or less long contacts with these glomerular suspensions. We studied isolated glomeruli diameter evolution according to reagent dose (0,25 to 10 mg/ml) and its contact length (1, 5, 10 minutes). If the diameter remains practically constant during all the period for the lowest doses, it begins to decrease after the 5th minute for higher (1 and 2,5 mg/ml) and cracks up in the first minutes for the biggest ones (5 and 10 mg/ml). Pharmacologic and toxic actions are discussed ; hypothesis of a toxic effect at smooth muscular cells level is proposed.", "contents": "[Demonstration of the myotoxic effect of theophylline on the isolated kidney glomerulus of the rat]. After confirmation of the intense and very fast myorelaxant effect of theophylline on isolated glomeruli, xanthic reagent myotoxic effects are shown during more or less long contacts with these glomerular suspensions. We studied isolated glomeruli diameter evolution according to reagent dose (0,25 to 10 mg/ml) and its contact length (1, 5, 10 minutes). If the diameter remains practically constant during all the period for the lowest doses, it begins to decrease after the 5th minute for higher (1 and 2,5 mg/ml) and cracks up in the first minutes for the biggest ones (5 and 10 mg/ml). Pharmacologic and toxic actions are discussed ; hypothesis of a toxic effect at smooth muscular cells level is proposed."} {"id": "PMID:161187", "title": "[Immunofluorescence demonstration of somatostatin-containing cells in the digestive tract of the monkeys irus, Macaca Papio hamadryas and Cercopithecus aethiops].", "content": "Indirect immunofluorescence technique with antisomatostatin serum has allowed us to detect somatostatin containing cells in the gastro-intestinal tract of three species of monkeys : Macacus irus, Papio hamadryas and Cercopithecus aethiops. These cells are localized only in the stomach, in the duodenum, and in the jejunum-ileum. No somatostatin cells were encountered in the esophagus and in the colon. The maximum of somatostatin positive cells is localized in the duodenum, as well in the Lieberk\u00fchn's glands as in the Brunner's glands. These cells are always separated from each other ; they were found only in glandular epithelium ; no immunopositive cells were observed in the surface epithelium. No morphological or numerical differences were noted between the three species of monkeys.", "contents": "[Immunofluorescence demonstration of somatostatin-containing cells in the digestive tract of the monkeys irus, Macaca Papio hamadryas and Cercopithecus aethiops]. Indirect immunofluorescence technique with antisomatostatin serum has allowed us to detect somatostatin containing cells in the gastro-intestinal tract of three species of monkeys : Macacus irus, Papio hamadryas and Cercopithecus aethiops. These cells are localized only in the stomach, in the duodenum, and in the jejunum-ileum. No somatostatin cells were encountered in the esophagus and in the colon. The maximum of somatostatin positive cells is localized in the duodenum, as well in the Lieberk\u00fchn's glands as in the Brunner's glands. These cells are always separated from each other ; they were found only in glandular epithelium ; no immunopositive cells were observed in the surface epithelium. No morphological or numerical differences were noted between the three species of monkeys."} {"id": "PMID:161188", "title": "[SAMBA : a cytophotometer coupled to a computer for the purpose of the automatic study of cell kinetics and the recognition of cell types].", "content": "The system SAMBA has been designed for automatic analysis of biological images, at the cellular or subcellular level. The examination is performed at the maximum resolution power of the microscope. It enables to discriminate by means of a pool of morphological and densitometrical parameters, between cells in the different phases of the cell cycle, or between cells belonging to various types in heterogeneous populations. Other recognition programs are at present beeing in progress, in order to promote the use of SAMBA in other fields of fundamental research and clinical application. Owing to the minicomputer now in use, SAMBA is an autonomous system, capable of beeing routinely used in diagnostic centers.", "contents": "[SAMBA : a cytophotometer coupled to a computer for the purpose of the automatic study of cell kinetics and the recognition of cell types]. The system SAMBA has been designed for automatic analysis of biological images, at the cellular or subcellular level. The examination is performed at the maximum resolution power of the microscope. It enables to discriminate by means of a pool of morphological and densitometrical parameters, between cells in the different phases of the cell cycle, or between cells belonging to various types in heterogeneous populations. Other recognition programs are at present beeing in progress, in order to promote the use of SAMBA in other fields of fundamental research and clinical application. Owing to the minicomputer now in use, SAMBA is an autonomous system, capable of beeing routinely used in diagnostic centers."} {"id": "PMID:161189", "title": "[Effects of microwaves on the cellular immune response of Swiss mice].", "content": "Biological effects of microwaves (2450 MHz) were studied on cellular immune response of Swiss mouse. The obtained results show an increase of MIF, PFC and Phagocytosis values after microwaves irradiation.", "contents": "[Effects of microwaves on the cellular immune response of Swiss mice]. Biological effects of microwaves (2450 MHz) were studied on cellular immune response of Swiss mouse. The obtained results show an increase of MIF, PFC and Phagocytosis values after microwaves irradiation."} {"id": "PMID:161190", "title": "[Diminution of blood and hepatic cholesterol induced by an apple-supplemented diet in the hamster. Trials in man].", "content": "The effects of an apple-supplemented diet on plasma and liver cholesterol were investigated in two strains of Hamster, a normal one and another which exhibits a spontaneous accumulation of cholesteryl esters in the liver (FEC animals). Adding of apples to the standard diet promoted a 20 % decrease of cholesterolemia in normal animals and normalized the high level of plasma cholesterol in the FEC animals. Similarly, the cholesterol content of the liver was diminished. The levels of cholesteryl esters were strongly lowered, threefold and tenfold respectively in normal and in FEC animals. Incorporation of labelled mevalonate into cholesterol was increased, but esterification of the neosynthesized sterol was markedly reduced in the liver from FEC animals. In human daily ingestion of apples caused a significative reduction (16 %) of cholesterolemia.", "contents": "[Diminution of blood and hepatic cholesterol induced by an apple-supplemented diet in the hamster. Trials in man]. The effects of an apple-supplemented diet on plasma and liver cholesterol were investigated in two strains of Hamster, a normal one and another which exhibits a spontaneous accumulation of cholesteryl esters in the liver (FEC animals). Adding of apples to the standard diet promoted a 20 % decrease of cholesterolemia in normal animals and normalized the high level of plasma cholesterol in the FEC animals. Similarly, the cholesterol content of the liver was diminished. The levels of cholesteryl esters were strongly lowered, threefold and tenfold respectively in normal and in FEC animals. Incorporation of labelled mevalonate into cholesterol was increased, but esterification of the neosynthesized sterol was markedly reduced in the liver from FEC animals. In human daily ingestion of apples caused a significative reduction (16 %) of cholesterolemia."} {"id": "PMID:161191", "title": "[A postsynaptic type nodal axon].", "content": "A node of Ranvier in which the nodal axon is post-synaptic to a terminal axon was found in the cerebral cortex of the rat near by an epileptic focus. This type of synapse is in itself a rare observation but is also worthwile considering because of its vicinity with this focus.", "contents": "[A postsynaptic type nodal axon]. A node of Ranvier in which the nodal axon is post-synaptic to a terminal axon was found in the cerebral cortex of the rat near by an epileptic focus. This type of synapse is in itself a rare observation but is also worthwile considering because of its vicinity with this focus."} {"id": "PMID:161192", "title": "[Effect of vinblastine on the blast population of the thymus subcapsular zone in the mouse].", "content": "It is well admitted that blast cells of the thymic subcapsular zone play an important role in murine leukemogenesis. Previous ultrastructural investigations have revealed the morphological heterogeneity of this population which is formed by lymphoblasts, X cells and ring shaped nucleolus cells. These aspects could correspond to different positions in the cell cycle of an unique cell type. After administration of vinblastine, a drug blocking mitosis in metaphasis, the percentage of lymphoblasts decreases whereas the percentage of X cells increases. There is no modification of the number of ring-shaped nucleolus cells. This suggests that at least a part of lymphoblasts gives rise to x cells.", "contents": "[Effect of vinblastine on the blast population of the thymus subcapsular zone in the mouse]. It is well admitted that blast cells of the thymic subcapsular zone play an important role in murine leukemogenesis. Previous ultrastructural investigations have revealed the morphological heterogeneity of this population which is formed by lymphoblasts, X cells and ring shaped nucleolus cells. These aspects could correspond to different positions in the cell cycle of an unique cell type. After administration of vinblastine, a drug blocking mitosis in metaphasis, the percentage of lymphoblasts decreases whereas the percentage of X cells increases. There is no modification of the number of ring-shaped nucleolus cells. This suggests that at least a part of lymphoblasts gives rise to x cells."} {"id": "PMID:161193", "title": "[Orthosympathetic reaction during paroxysmal asphyxia in the rat].", "content": "Acute hypercapnic hypoxia provoked by the ligature of the trachea kills the rat in 3 to 5 minutes. Catecholaminemia is immediately increased by adrenaline release from the adrenal medulla for the largest part. Catecholamine contents of the suprarenal glands is not decreased at the time of death.", "contents": "[Orthosympathetic reaction during paroxysmal asphyxia in the rat]. Acute hypercapnic hypoxia provoked by the ligature of the trachea kills the rat in 3 to 5 minutes. Catecholaminemia is immediately increased by adrenaline release from the adrenal medulla for the largest part. Catecholamine contents of the suprarenal glands is not decreased at the time of death."} {"id": "PMID:161194", "title": "[Role of host cells in suppression of the in vivo multiplication of Ehrlich's ascitic cancer cells by the virus-inhibiting factor or interferon].", "content": "Neither activation nor depression of murine peritoneal macrophages or lymphoid cells modified the suppressive effect of the virus-inhibiting factor or interferon on the multiplication of Ehrlich's ascitic cancer cells in mice.", "contents": "[Role of host cells in suppression of the in vivo multiplication of Ehrlich's ascitic cancer cells by the virus-inhibiting factor or interferon]. Neither activation nor depression of murine peritoneal macrophages or lymphoid cells modified the suppressive effect of the virus-inhibiting factor or interferon on the multiplication of Ehrlich's ascitic cancer cells in mice."} {"id": "PMID:161195", "title": "[Effect of the virus-inhibiting factor or interferon on the division and differentiation of murine leukemic cells].", "content": "Myeloblasts of a clone originating from a spontaneous myeloid leukemia in mice were induced to form macrophages by the virus-inhibiting factor or interferon or its inducers such as Newcastle disease virus and double-stranded RNA.", "contents": "[Effect of the virus-inhibiting factor or interferon on the division and differentiation of murine leukemic cells]. Myeloblasts of a clone originating from a spontaneous myeloid leukemia in mice were induced to form macrophages by the virus-inhibiting factor or interferon or its inducers such as Newcastle disease virus and double-stranded RNA."} {"id": "PMID:161196", "title": "[Purification and comparison of quail and chicken pepsinogens].", "content": "Pepsinogens of quail and chick, specific to adult proventriculus, were purified and their properties were compared. These two pepsinogens are similar in regard to enzymological characters, amino acid compositions, and immunological characters.", "contents": "[Purification and comparison of quail and chicken pepsinogens]. Pepsinogens of quail and chick, specific to adult proventriculus, were purified and their properties were compared. These two pepsinogens are similar in regard to enzymological characters, amino acid compositions, and immunological characters."} {"id": "PMID:161197", "title": "[Effects of 2 water-soluble contrast media, meglumine iothalamate (Conray) and meglumine iocarmate (Dimer-X), on the electric activity of identifiable giant neurons of the African giant snail (Achatina fulica Ferussac)].", "content": "The influences of two water soluble contrast media, meglumine iothalamate and meglumine iocarmate, on the neuronal excitability and on the neuronal sensitivity to putative transmitters were examined in comparison with those of sucrose using two identifiable giant neurones of Achatina fulica F\u00e9russac (the TAN and the PON). A relatively low increase of osmotic pressure of the extracellular fluid, produced by the application of contrast media, reversed the Cl- dependent inhibition caused by a putative transmitter. The same increase of this osmotic pressure, however, did not influence the Cl- independent inhibition and the excitation of the neurone examined. The hyperpolarization of neuromembrane was caused by an increase of osmotic pressure of the extracellular fluid. Its relatively high increase was necessary to make spontaneous spike discharges disappear totally. All effects of the two contrast media, observed in this study, were due to the increase of osmotic pressure of the extracellular fluid ; no specific effect of the contrast media containing the iodine on the indicators used was observed.", "contents": "[Effects of 2 water-soluble contrast media, meglumine iothalamate (Conray) and meglumine iocarmate (Dimer-X), on the electric activity of identifiable giant neurons of the African giant snail (Achatina fulica Ferussac)]. The influences of two water soluble contrast media, meglumine iothalamate and meglumine iocarmate, on the neuronal excitability and on the neuronal sensitivity to putative transmitters were examined in comparison with those of sucrose using two identifiable giant neurones of Achatina fulica F\u00e9russac (the TAN and the PON). A relatively low increase of osmotic pressure of the extracellular fluid, produced by the application of contrast media, reversed the Cl- dependent inhibition caused by a putative transmitter. The same increase of this osmotic pressure, however, did not influence the Cl- independent inhibition and the excitation of the neurone examined. The hyperpolarization of neuromembrane was caused by an increase of osmotic pressure of the extracellular fluid. Its relatively high increase was necessary to make spontaneous spike discharges disappear totally. All effects of the two contrast media, observed in this study, were due to the increase of osmotic pressure of the extracellular fluid ; no specific effect of the contrast media containing the iodine on the indicators used was observed."} {"id": "PMID:161198", "title": "[Effect of oligopeptides containing L-Phe, L-Tyr, L-Trp, L-His or L-Met on the excitability of the 2 giant neurons of the African giant snail (Achatina fulica Ferussac)].", "content": "Effects of about ninety oligopeptides, containing L-Phe, L-Tyr, L-Trp, L-His and L-Met, on the excitability of two identifiable giant neurones (the PON, periodically oscillating neurone ; and the TAN, tonically autoactive neurone) of Achatine fulica F\u00e9russac were examined. Three oligopeptides, L-Lys-L-Phe-L-Tyr, L-Phe-L-Tyr and L-Phe-L-Trp, showed an inhibitory effect on the PON. However, this effect on the PON was weaker than that of the same three peptides on the TAN. [The latter has been reported in previous papers (1 to 3)]. Besides the three oligopeptides mentioned, four peptides, L-Phe-L-Phe, L-Phe-L-Phe-L-Phe, L-Tyr-L-Tyr and L-Tyr-L-Tyr-LTyr, still showed a weak inhibitory effect on the TAN in a high concentration.", "contents": "[Effect of oligopeptides containing L-Phe, L-Tyr, L-Trp, L-His or L-Met on the excitability of the 2 giant neurons of the African giant snail (Achatina fulica Ferussac)]. Effects of about ninety oligopeptides, containing L-Phe, L-Tyr, L-Trp, L-His and L-Met, on the excitability of two identifiable giant neurones (the PON, periodically oscillating neurone ; and the TAN, tonically autoactive neurone) of Achatine fulica F\u00e9russac were examined. Three oligopeptides, L-Lys-L-Phe-L-Tyr, L-Phe-L-Tyr and L-Phe-L-Trp, showed an inhibitory effect on the PON. However, this effect on the PON was weaker than that of the same three peptides on the TAN. [The latter has been reported in previous papers (1 to 3)]. Besides the three oligopeptides mentioned, four peptides, L-Phe-L-Phe, L-Phe-L-Phe-L-Phe, L-Tyr-L-Tyr and L-Tyr-L-Tyr-LTyr, still showed a weak inhibitory effect on the TAN in a high concentration."} {"id": "PMID:161213", "title": "Chronic immune complex disease in mice: the role of antibody affinity.", "content": "Two lines of mice selectively bred for producing high and low affinity antibody to protein antigens were repeatedly injected with human serum albumin and the severity and pattern of immune complex disease induced in this way was studied in the two lines. In low affinity mice, there was a greater intensity of deposits in the glomeruli shown by immunofluorescence, and more antibody was eluted from kidney homogenates compared to high affinity line mice. In the low affinity mice, complexes were mainly on the basement membrane whereas in high affinity mice, the localization of immune complexes was predominantly mesangial. However, no significant difference in glomerular filtration rates between the two lines was obtained. The immunopathological significance of antibody affinity is discussed in the light of these results.", "contents": "Chronic immune complex disease in mice: the role of antibody affinity. Two lines of mice selectively bred for producing high and low affinity antibody to protein antigens were repeatedly injected with human serum albumin and the severity and pattern of immune complex disease induced in this way was studied in the two lines. In low affinity mice, there was a greater intensity of deposits in the glomeruli shown by immunofluorescence, and more antibody was eluted from kidney homogenates compared to high affinity line mice. In the low affinity mice, complexes were mainly on the basement membrane whereas in high affinity mice, the localization of immune complexes was predominantly mesangial. However, no significant difference in glomerular filtration rates between the two lines was obtained. The immunopathological significance of antibody affinity is discussed in the light of these results."} {"id": "PMID:161214", "title": "Behaviour of human immunoregulatory cells in culture. I. Variables requiring consideration for clinical studies.", "content": "The suppressor function of lymphocytes stimulated with concanavalin A (Con A) provides a potential method for examining disorders of immunoregulation. Clinical application, however, requires definition of the culture conditions that influence the expression of normal suppressor cell activity. In the present studies culture conditions were modified until a sensitive assay for non-specific suppressor cell function was reproducible utilizing the response to varying doses of phytohaemagglutinin (PHA) as an indicator system. Practical conclusions included (1) that sensitivity was not lost if the suppressor cells and responder cells were allogenic; (2) that fresh responder cells were as sensitive as precultured responder cells; (3) that a wide range of Con A concentrations could induce suppressor activity; and (4) that the sensitivity of the assay was much enhanced by using suboptimal mitogen doses of PHA. Twelve percent of normal subjects gave false negative results but these could be avoided by studying cells at more than one time point after stimulation with Con A. Cells resting in culture for 7 days could be induced to suppress after stimulation with Con A and these suppressor cells were very sensitive to pharmacological doses of dexamethasone. Studies utilizing different times of cell pre-incubation before Con A stimulation and different periods of exposure to Con A revealed fluctuation in the induction of suppression that may represent alternating periods of suppression and amplifying activity among stimulated cells in vitro. Such variations will need to be taken into account in the application of this type of assay to clinical studies seeking disordered immunoregulation.", "contents": "Behaviour of human immunoregulatory cells in culture. I. Variables requiring consideration for clinical studies. The suppressor function of lymphocytes stimulated with concanavalin A (Con A) provides a potential method for examining disorders of immunoregulation. Clinical application, however, requires definition of the culture conditions that influence the expression of normal suppressor cell activity. In the present studies culture conditions were modified until a sensitive assay for non-specific suppressor cell function was reproducible utilizing the response to varying doses of phytohaemagglutinin (PHA) as an indicator system. Practical conclusions included (1) that sensitivity was not lost if the suppressor cells and responder cells were allogenic; (2) that fresh responder cells were as sensitive as precultured responder cells; (3) that a wide range of Con A concentrations could induce suppressor activity; and (4) that the sensitivity of the assay was much enhanced by using suboptimal mitogen doses of PHA. Twelve percent of normal subjects gave false negative results but these could be avoided by studying cells at more than one time point after stimulation with Con A. Cells resting in culture for 7 days could be induced to suppress after stimulation with Con A and these suppressor cells were very sensitive to pharmacological doses of dexamethasone. Studies utilizing different times of cell pre-incubation before Con A stimulation and different periods of exposure to Con A revealed fluctuation in the induction of suppression that may represent alternating periods of suppression and amplifying activity among stimulated cells in vitro. Such variations will need to be taken into account in the application of this type of assay to clinical studies seeking disordered immunoregulation."} {"id": "PMID:161220", "title": "[The diagnostic value of various stiffness indices in the evaluation of the diastolic properties of the left ventricle].", "content": "The results are presented of simulated calculations obtained with the aid of a continuum model of the left ventricle in a passive state on the basis of a nonlinear elasticity theory. Various empirical indexes of left ventricular rigidity are calculated from modelled diastolic pressure/volume curves, and are compared with myocardial elasticity indicators. With respect to sensitivity and specificity, as the best there were found the volume-standardized Diamond index (d[lnP]/dV)V0 and the Laird index d(lnP)/d/lnV). The indexes are calculated from two parts of enddiastolic pressure/volume values. An analysis of clinically measured values confirmed the model predictions.", "contents": "[The diagnostic value of various stiffness indices in the evaluation of the diastolic properties of the left ventricle]. The results are presented of simulated calculations obtained with the aid of a continuum model of the left ventricle in a passive state on the basis of a nonlinear elasticity theory. Various empirical indexes of left ventricular rigidity are calculated from modelled diastolic pressure/volume curves, and are compared with myocardial elasticity indicators. With respect to sensitivity and specificity, as the best there were found the volume-standardized Diamond index (d[lnP]/dV)V0 and the Laird index d(lnP)/d/lnV). The indexes are calculated from two parts of enddiastolic pressure/volume values. An analysis of clinically measured values confirmed the model predictions."} {"id": "PMID:161221", "title": "Amino acid analogues: uptake, pool formation and incorporation of phenylalanine and two halogenated derivatives in cultured mammalian cells.", "content": "HeLa cells take up Phe and two of its ring halogenated derivatives (pFPhe and pClPhe) with rpaidity, concentrating them against the external medium both at 4 and 37 degrees C. The majority of amino acid (greater than 90%) is accumulated without energy expenditures at 4 degrees C, and can be quickly discharged by normal cell washing procedures in saline. At 37 degrees C the freely-diffusible (FDP) pool is accompanied by another which develops more slowly and cannot diffuse out freely during washings with saline but is extractable with trichloracetic acid (the slowly-diffusible pool, SDP, or more conventionally, the acid-soluble pool). Both of the analogues produced larger pools of the latter type than Phe itself from external concentrations ranging from 10(-5) to 10(-3) M. The incorporation of pFPhe into proteins over these same concentrations ranged from 30 to 90--95% of Phe incorporation, whereas pClPhe showed negligible incorporation. From these and similar analyses it can be concluded that amino acid pools form largely independently of protein synthesis, but bear a close relationship with the external amino acid concentration. The fraction of total uptake into cellular pools entering the SDP was relatively constant over a wide range of external concentrations. pFPhe incorporation into cellular proteins produced the same labelling distribution of Phe. It appears to ener all proteins, the vast majority of which have similar half-lives and turnover rates to Phe proteins. In competition, little or no interference was experienced between the analogue and Phe in uptake and pool formation until excessive amounts of one or the other were present (50--100x). By contrast, incorporation of pFPhe into protein was markedly reduced by the presence of Phe. However, the development of normal or large pools of pFPhe or Phe in cells prior to 3H-Phe incorporation did not affect the linear incorporation pattern of the radioisotope into protein. The relationship of pools to protein synthesis is discussed, and it is concluded that, although the SDP could contain potential precursor molecules for protein synthesis, it does not usually act as the direct supplier of amino acid for protein synthesis. Alternative explanations for precursor supply are discussed.", "contents": "Amino acid analogues: uptake, pool formation and incorporation of phenylalanine and two halogenated derivatives in cultured mammalian cells. HeLa cells take up Phe and two of its ring halogenated derivatives (pFPhe and pClPhe) with rpaidity, concentrating them against the external medium both at 4 and 37 degrees C. The majority of amino acid (greater than 90%) is accumulated without energy expenditures at 4 degrees C, and can be quickly discharged by normal cell washing procedures in saline. At 37 degrees C the freely-diffusible (FDP) pool is accompanied by another which develops more slowly and cannot diffuse out freely during washings with saline but is extractable with trichloracetic acid (the slowly-diffusible pool, SDP, or more conventionally, the acid-soluble pool). Both of the analogues produced larger pools of the latter type than Phe itself from external concentrations ranging from 10(-5) to 10(-3) M. The incorporation of pFPhe into proteins over these same concentrations ranged from 30 to 90--95% of Phe incorporation, whereas pClPhe showed negligible incorporation. From these and similar analyses it can be concluded that amino acid pools form largely independently of protein synthesis, but bear a close relationship with the external amino acid concentration. The fraction of total uptake into cellular pools entering the SDP was relatively constant over a wide range of external concentrations. pFPhe incorporation into cellular proteins produced the same labelling distribution of Phe. It appears to ener all proteins, the vast majority of which have similar half-lives and turnover rates to Phe proteins. In competition, little or no interference was experienced between the analogue and Phe in uptake and pool formation until excessive amounts of one or the other were present (50--100x). By contrast, incorporation of pFPhe into protein was markedly reduced by the presence of Phe. However, the development of normal or large pools of pFPhe or Phe in cells prior to 3H-Phe incorporation did not affect the linear incorporation pattern of the radioisotope into protein. The relationship of pools to protein synthesis is discussed, and it is concluded that, although the SDP could contain potential precursor molecules for protein synthesis, it does not usually act as the direct supplier of amino acid for protein synthesis. Alternative explanations for precursor supply are discussed."} {"id": "PMID:161216", "title": "The predictive utility of the orthopedic examination in identifying the low back pain patient with hysterical personality features.", "content": "Physical examination of the patient with low back pain routinely includes a number of tests which are useful clinically to the orthopedist as suggestive of the presence of hysteria or malingering. These include tests of light touch differences medially and laterally in the same foot or leg, vibratory sensation in the lower extremities, forward flexion, straight-leg raising differences between the supine and sitting positions, and the Burns' bench test. The present study examined the specific predictive utility of these tests individually and as a composite battery in identifying low back pain patients with hysterical personality features. Twenty-five postoperative lumbar laminectomy and diskectomy patients were administered the MMPI and evaluated by physical examination. Silight to moderate correlations were found for each of the subtests with a Composite Hysteria Index derived from the MMPI. The predictability was improved by the use of a weighted combination of the individual tests obtained by multiple regression analysis. The results lend empirical support to: the predictive value of these clinical tests in definitively identifying 60% of those low back pain patients with hysterical personality features; decision rules for use in clinical practice were also developed.", "contents": "The predictive utility of the orthopedic examination in identifying the low back pain patient with hysterical personality features. Physical examination of the patient with low back pain routinely includes a number of tests which are useful clinically to the orthopedist as suggestive of the presence of hysteria or malingering. These include tests of light touch differences medially and laterally in the same foot or leg, vibratory sensation in the lower extremities, forward flexion, straight-leg raising differences between the supine and sitting positions, and the Burns' bench test. The present study examined the specific predictive utility of these tests individually and as a composite battery in identifying low back pain patients with hysterical personality features. Twenty-five postoperative lumbar laminectomy and diskectomy patients were administered the MMPI and evaluated by physical examination. Silight to moderate correlations were found for each of the subtests with a Composite Hysteria Index derived from the MMPI. The predictability was improved by the use of a weighted combination of the individual tests obtained by multiple regression analysis. The results lend empirical support to: the predictive value of these clinical tests in definitively identifying 60% of those low back pain patients with hysterical personality features; decision rules for use in clinical practice were also developed."} {"id": "PMID:161217", "title": "Sit-up exercises: an electromyographic study.", "content": "The effect of 5 different sit-up regimens on the abdominal muscle activity were investigated by electromyography as well as the degree of lumbar flexion required with each type of sit-up. In the long-lying position the rectus abdominus muscles were only active an average of 34% of the sit-up cycle. The greatest duration of activity (90%) was found in the shoulder lift hook-lying (knees flexed) sit-up in which the subject elevates the trunk to the point where the scapula is lifted from the mat. In addition, this sit-up requires minimal flexion of the lumbar spine (3 degrees versus 38 degrees) and is less likely to result in increased forces across the lumbar disk. The evidence is that this sit-up is the most effective in terms of abdominal muscle activity and the safest in terms of causing lumbar spinal flexion.", "contents": "Sit-up exercises: an electromyographic study. The effect of 5 different sit-up regimens on the abdominal muscle activity were investigated by electromyography as well as the degree of lumbar flexion required with each type of sit-up. In the long-lying position the rectus abdominus muscles were only active an average of 34% of the sit-up cycle. The greatest duration of activity (90%) was found in the shoulder lift hook-lying (knees flexed) sit-up in which the subject elevates the trunk to the point where the scapula is lifted from the mat. In addition, this sit-up requires minimal flexion of the lumbar spine (3 degrees versus 38 degrees) and is less likely to result in increased forces across the lumbar disk. The evidence is that this sit-up is the most effective in terms of abdominal muscle activity and the safest in terms of causing lumbar spinal flexion."} {"id": "PMID:161225", "title": "The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymes.", "content": "One-leg exercise of 5 weeks duration in 10 healthy middleaged women resulted in a significant increment of muscle force in the exercising leg and in a less, but at some angular velocities also significant, increase in the nonexercising leg. The thickness of subcutaneous tissue measured by ultrasound and skinfold caliper decreased, while muscle thickness increased in the exercising leg only. The increased thickness of muscle tissue was associated with an increase in the relative number and relative fiber area of type II fibers in the exercising leg. The mean fiber area of type IIB fibers increased significantly as well as the activity of lactate dehydrogenase and myokinase. The decrease of thickness of subcutaneous adipose tissue was not associated with a significant decrease in fat cell size and was probably due to geometrical factors secondary to hypertrophy of the underlying muscle. It is concluded that the relationship between lean and fat components of the human thigh is significantly influenced by changes in the activity of the thigh skeletal muscles, but a local dynamic strength training program can hardly be used for local emptying of the fat depot over the exercising muscles.", "contents": "The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymes. One-leg exercise of 5 weeks duration in 10 healthy middleaged women resulted in a significant increment of muscle force in the exercising leg and in a less, but at some angular velocities also significant, increase in the nonexercising leg. The thickness of subcutaneous tissue measured by ultrasound and skinfold caliper decreased, while muscle thickness increased in the exercising leg only. The increased thickness of muscle tissue was associated with an increase in the relative number and relative fiber area of type II fibers in the exercising leg. The mean fiber area of type IIB fibers increased significantly as well as the activity of lactate dehydrogenase and myokinase. The decrease of thickness of subcutaneous adipose tissue was not associated with a significant decrease in fat cell size and was probably due to geometrical factors secondary to hypertrophy of the underlying muscle. It is concluded that the relationship between lean and fat components of the human thigh is significantly influenced by changes in the activity of the thigh skeletal muscles, but a local dynamic strength training program can hardly be used for local emptying of the fat depot over the exercising muscles."} {"id": "PMID:161240", "title": "Lymphocyte response to autochthonous human solid tumor cells: relationship to histological types and tumor load.", "content": "Mixed lymphocyte--tumor cell cultures were made with materials from patients with various histological types of cancer. In 25 out of 89 patients, positive lymphocyte response to tumor cells was observed. There appeared to be an inverse relationship between the frequency of positive responses and extent of the disease. Patients with neuroblastoma, however, showed more frequent positive responses in cases of widespread disease. The data obtained may have valuable clinical implications, supporting the possibility of immunotherapy of cancer patients.", "contents": "Lymphocyte response to autochthonous human solid tumor cells: relationship to histological types and tumor load. Mixed lymphocyte--tumor cell cultures were made with materials from patients with various histological types of cancer. In 25 out of 89 patients, positive lymphocyte response to tumor cells was observed. There appeared to be an inverse relationship between the frequency of positive responses and extent of the disease. Patients with neuroblastoma, however, showed more frequent positive responses in cases of widespread disease. The data obtained may have valuable clinical implications, supporting the possibility of immunotherapy of cancer patients."} {"id": "PMID:161241", "title": "Frequency-dependent selection at the PGM-1 locus of Drosophila pseudoobscura.", "content": "Frequency-dependent fitness was studied at the Pgm-1 locus of Drosophila pseudoobscura with respect to two fitness components: rate of development and larva-to-adult survival. The Pgm-1 locus is very polymorphic with only two alleles, Pgm-1(100) and Pgm-1(104), occurring at high frequencies. For each of these two alleles, 20 homozygous strains were obtained from a sample of 1,140 wild-inseminated females. First-instar larvae of the two genotypes were combined in a set of eight different frequencies: 0.0, 0.10, 0.25, 0.40, 0.60, 0.75, 0.90, and 1.0. Frequency-dependent fitness effects were observed for the two survival-related fitness components examined: larvae of the less common genotype develop faster and have a higher probability of survival than larvae of the more common genotype. The rate of survival at intermediate genotypic frequencies is similar to that in pure cultures. If selection acted solely as frequency-dependent effects on survival-related components of fitness, the equilibrium frequency of the Pgm-1(100) allele would be 0.615 for a two-genotype system, which fits an observed frequency range for this allele in nature between 0.55 and 0.71. Experimentally created linkage disequilibrium was excluded from the experiment by using a large number of independent strains. It is nevertheless possible that the frequency-dependent selection may not affect the Pgm-1 locus per se, but may reflect a linkage disequilibrium present in the natural population. Even if this were the case, the frequency-dependent selection could affect the frequency of the Pgm-1 alleles in nature.", "contents": "Frequency-dependent selection at the PGM-1 locus of Drosophila pseudoobscura. Frequency-dependent fitness was studied at the Pgm-1 locus of Drosophila pseudoobscura with respect to two fitness components: rate of development and larva-to-adult survival. The Pgm-1 locus is very polymorphic with only two alleles, Pgm-1(100) and Pgm-1(104), occurring at high frequencies. For each of these two alleles, 20 homozygous strains were obtained from a sample of 1,140 wild-inseminated females. First-instar larvae of the two genotypes were combined in a set of eight different frequencies: 0.0, 0.10, 0.25, 0.40, 0.60, 0.75, 0.90, and 1.0. Frequency-dependent fitness effects were observed for the two survival-related fitness components examined: larvae of the less common genotype develop faster and have a higher probability of survival than larvae of the more common genotype. The rate of survival at intermediate genotypic frequencies is similar to that in pure cultures. If selection acted solely as frequency-dependent effects on survival-related components of fitness, the equilibrium frequency of the Pgm-1(100) allele would be 0.615 for a two-genotype system, which fits an observed frequency range for this allele in nature between 0.55 and 0.71. Experimentally created linkage disequilibrium was excluded from the experiment by using a large number of independent strains. It is nevertheless possible that the frequency-dependent selection may not affect the Pgm-1 locus per se, but may reflect a linkage disequilibrium present in the natural population. Even if this were the case, the frequency-dependent selection could affect the frequency of the Pgm-1 alleles in nature."} {"id": "PMID:161242", "title": "Some properties of site-specific and general recombination inferred from int-initiated exchanges by bacteriophage lambda.", "content": "The site-specific recombination at the attachment site for prophage integration might proceed by two general mechanisms: (1) a concerted reaction without a free intermediate; (2) a sequential mechanism differing from typical general recombination only by an inability of the cross-strand intermediate structure to migrate into the region of nonhomology adjacent to the attachment site. The blocked-migration model predicts frequent genetic exchange in the int xis region near the attachment site if Int-mediated recombination occurs between lambda phage with homologous attachment sites. We find such additional int xis exchanges, but only at very low frequency (1% of the Int-mediated recombination). We conclude that the resolution point only rarely moves away from the initial crossover point specified by Int and, therefore, that the Int reaction is mainly concerted. We interpret the rare additional int xis recombinants as indicative of occasional branch migration from an initial Int-mediated crossover. The frequency of the rare int xis recombinants is not simply related to distance from the attachment site to an int- or xis- mutation, suggesting that the heteroduplex distance is often at least a gene in length. The frequency of these additional exchanges is also not a strong function of distance between two mutations; from this we conclude that the resolution to the observed recombinant structure in the sequential cases occurs often by mismatch repair. We have found no marked effect of mutations in the bacterial recA, recB, recC, recF, or recL genes on the frequency of the int xis recombinants; this may indicate that none of these genes specifies a product uniquely required for resolution of a cross-strand intermediate.", "contents": "Some properties of site-specific and general recombination inferred from int-initiated exchanges by bacteriophage lambda. The site-specific recombination at the attachment site for prophage integration might proceed by two general mechanisms: (1) a concerted reaction without a free intermediate; (2) a sequential mechanism differing from typical general recombination only by an inability of the cross-strand intermediate structure to migrate into the region of nonhomology adjacent to the attachment site. The blocked-migration model predicts frequent genetic exchange in the int xis region near the attachment site if Int-mediated recombination occurs between lambda phage with homologous attachment sites. We find such additional int xis exchanges, but only at very low frequency (1% of the Int-mediated recombination). We conclude that the resolution point only rarely moves away from the initial crossover point specified by Int and, therefore, that the Int reaction is mainly concerted. We interpret the rare additional int xis recombinants as indicative of occasional branch migration from an initial Int-mediated crossover. The frequency of the rare int xis recombinants is not simply related to distance from the attachment site to an int- or xis- mutation, suggesting that the heteroduplex distance is often at least a gene in length. The frequency of these additional exchanges is also not a strong function of distance between two mutations; from this we conclude that the resolution to the observed recombinant structure in the sequential cases occurs often by mismatch repair. We have found no marked effect of mutations in the bacterial recA, recB, recC, recF, or recL genes on the frequency of the int xis recombinants; this may indicate that none of these genes specifies a product uniquely required for resolution of a cross-strand intermediate."} {"id": "PMID:161244", "title": "A simple technique for the isolation of deletion mutants of phage lambda.", "content": "We describe a simple technique for isolating deletion mutants of phage lambda and use it to dissect a cloned fragment of foreign DNA. The technique is based on our previous finding that the normally essential product of lambda head gene D is dispensible for phage growth if the DNA content of the phage is less than 82% that of lambda wild-type (Sternberg and Weisberg, 1977). A significant fraction of the few phage that form plaques when a D amber mutant is plated on a nonsuppressing host contains deletions that reduce the phage chromosome size to less than 82% that of wild-type. It is possible to isolate deletions ranging in size from less than 1.5 kb to 14 kb (3 to 27% of wild-type lambda), and the size range can be restricted by an appropriate choice of the DNA content of the starting phage. This method, unlike the older EDTA or heat resistance methods, permits the scoring of deletions because of the absence of phenotypic variants. We investigated the effect of several host and phage mutations on deletion frequency and type and have determined that a host polA mutation increases the frequency of deletions about 30-50-fold without changing the type of deletions. A host mutD mutation or thymine deprivation increases deletion frequency about 10-fold. In contrast, a host ligts mutation has no effect on the frequency of deletions. We have also determined that the size of the smallest lambda chromosome packageable in a plaque-forming phage particle is 72-73% that of lambda wild-type.", "contents": "A simple technique for the isolation of deletion mutants of phage lambda. We describe a simple technique for isolating deletion mutants of phage lambda and use it to dissect a cloned fragment of foreign DNA. The technique is based on our previous finding that the normally essential product of lambda head gene D is dispensible for phage growth if the DNA content of the phage is less than 82% that of lambda wild-type (Sternberg and Weisberg, 1977). A significant fraction of the few phage that form plaques when a D amber mutant is plated on a nonsuppressing host contains deletions that reduce the phage chromosome size to less than 82% that of wild-type. It is possible to isolate deletions ranging in size from less than 1.5 kb to 14 kb (3 to 27% of wild-type lambda), and the size range can be restricted by an appropriate choice of the DNA content of the starting phage. This method, unlike the older EDTA or heat resistance methods, permits the scoring of deletions because of the absence of phenotypic variants. We investigated the effect of several host and phage mutations on deletion frequency and type and have determined that a host polA mutation increases the frequency of deletions about 30-50-fold without changing the type of deletions. A host mutD mutation or thymine deprivation increases deletion frequency about 10-fold. In contrast, a host ligts mutation has no effect on the frequency of deletions. We have also determined that the size of the smallest lambda chromosome packageable in a plaque-forming phage particle is 72-73% that of lambda wild-type."} {"id": "PMID:161245", "title": "Site-specific mutagenesis using synthetic oligodeoxyribonucleotide primers: I. Optimum conditions and minimum ologodeoxyribonucleotide length.", "content": "A synthetic oligodeoxyribonucleotide mismatched at a single nucleotide to a specific complementary site on wild-type circular phi X174 DNA can be used to produce a defined point mutation after in vitro incorporation into closed circular duplex DNA by elongation with DNA polymerase and ligation followed by transfection of Escherichia coli (Hutchison et al., 1978; Gillam et al., 1979). The present study is an investigation of the optimum conditions required for the oligodeoxyribonucleotide-primed reaction for production of transition and transversion mutations in phi X174 DNA, using the large (Klenow) fragment of E. coli DNA polymerase I. Under optimum conditions up to 39% of the progeny of transfection are the desired mutant and significant mutation is observed using a heptadeoxyribonucleotide.", "contents": "Site-specific mutagenesis using synthetic oligodeoxyribonucleotide primers: I. Optimum conditions and minimum ologodeoxyribonucleotide length. A synthetic oligodeoxyribonucleotide mismatched at a single nucleotide to a specific complementary site on wild-type circular phi X174 DNA can be used to produce a defined point mutation after in vitro incorporation into closed circular duplex DNA by elongation with DNA polymerase and ligation followed by transfection of Escherichia coli (Hutchison et al., 1978; Gillam et al., 1979). The present study is an investigation of the optimum conditions required for the oligodeoxyribonucleotide-primed reaction for production of transition and transversion mutations in phi X174 DNA, using the large (Klenow) fragment of E. coli DNA polymerase I. Under optimum conditions up to 39% of the progeny of transfection are the desired mutant and significant mutation is observed using a heptadeoxyribonucleotide."} {"id": "PMID:161246", "title": "Site-specific mutagenesis using synthetic oligodeoxyribonucleotide primers: II. In vitro selection of mutant DNA.", "content": "A method for the in vitro selection of mutant DNA has been devised as an adjunct to the recently developed method for the use of short enzymatically-synthesized oligodeoxyribonucleotides of defined sequence as site-specific mutagens for circular DNA. The selection method uses the mutating oligodeoxyribonucleotide as a primer for Escherichia coli DNA polymerase I (large fragment) under conditions where there is preferential interaction with mutant DNA template. After ligation using T4 DNA ligase, endonuclease S1 is used to degrade single-stranded non-mutant DNA leaving the desired mutant as closed circular duplex DNA. This paper describes the development of the method using mutants in phi X174 DNA as the model system. Studiies on the changes A leads to G and G leads to A at position 587 of phi X174 viral DNA (am3 to wild-type and its reversal) show that one or two cycles of selection can lead to a population of phage consisting of close to 100% mutants.", "contents": "Site-specific mutagenesis using synthetic oligodeoxyribonucleotide primers: II. In vitro selection of mutant DNA. A method for the in vitro selection of mutant DNA has been devised as an adjunct to the recently developed method for the use of short enzymatically-synthesized oligodeoxyribonucleotides of defined sequence as site-specific mutagens for circular DNA. The selection method uses the mutating oligodeoxyribonucleotide as a primer for Escherichia coli DNA polymerase I (large fragment) under conditions where there is preferential interaction with mutant DNA template. After ligation using T4 DNA ligase, endonuclease S1 is used to degrade single-stranded non-mutant DNA leaving the desired mutant as closed circular duplex DNA. This paper describes the development of the method using mutants in phi X174 DNA as the model system. Studiies on the changes A leads to G and G leads to A at position 587 of phi X174 viral DNA (am3 to wild-type and its reversal) show that one or two cycles of selection can lead to a population of phage consisting of close to 100% mutants."} {"id": "PMID:161255", "title": "[Reliability of double-contrast arthrography in detection of cartilage lesions of the knee joint (author's transl)].", "content": "The present work evaluates the method of double-contrast arthrography. To this end, cartilage damage on femoral condyles and tibial joint surfaces was studied in 1566 retrospectively evaluated double-contrast arthrographies. Operation reports and histological results served as control. The results of our own experiments demonstrate that even isolated cartilage lesions as small as 1 mm in diameter can be visualized.", "contents": "[Reliability of double-contrast arthrography in detection of cartilage lesions of the knee joint (author's transl)]. The present work evaluates the method of double-contrast arthrography. To this end, cartilage damage on femoral condyles and tibial joint surfaces was studied in 1566 retrospectively evaluated double-contrast arthrographies. Operation reports and histological results served as control. The results of our own experiments demonstrate that even isolated cartilage lesions as small as 1 mm in diameter can be visualized."} {"id": "PMID:161256", "title": "[Sonographic determination of liver volume. Problems, methods and practical significance of liver volume measurements (author's transl)].", "content": "A sonographic procedure is described which permits accurate determination of liver volume by simple means. Comparison between the sonographic measurements and volume determinations at autopsy carried out by water displacement of the isolated organ showed a statistical error of +/- 1.58% and for average liver volumes of 1,800 ml and 95% limits of confidence of -84 to +20 ml. Quantitation of liver size may be an important clinical measurement, e.g. in assessing the possibility of shunts in the lieno-portal system in portal hypertension with recurrent bleeding from oesophageal varices due to cirrhosis of the liver, for evaluating liver atrophy after shunts affecting the liver, for demonstrating liver size in right heart insufficiency and congestive states or for the control of the effectiveness of cytostatic drugs in lymphatic or haematological disease.", "contents": "[Sonographic determination of liver volume. Problems, methods and practical significance of liver volume measurements (author's transl)]. A sonographic procedure is described which permits accurate determination of liver volume by simple means. Comparison between the sonographic measurements and volume determinations at autopsy carried out by water displacement of the isolated organ showed a statistical error of +/- 1.58% and for average liver volumes of 1,800 ml and 95% limits of confidence of -84 to +20 ml. Quantitation of liver size may be an important clinical measurement, e.g. in assessing the possibility of shunts in the lieno-portal system in portal hypertension with recurrent bleeding from oesophageal varices due to cirrhosis of the liver, for evaluating liver atrophy after shunts affecting the liver, for demonstrating liver size in right heart insufficiency and congestive states or for the control of the effectiveness of cytostatic drugs in lymphatic or haematological disease."} {"id": "PMID:161257", "title": "[Computer tomography of the facial skeleton and pharyngeal space (author's transl)].", "content": "Seventy-five patients with histologically confirmed abnormalities of the facial skeleton and pharynx, including the mouth and base of the tongue, were examined by computer tomography. The advantages of simultaneous demonstration of the soft tissues and bones in localised space-occupying lesions are pointed out. Accurate comparison between pre-operative descriptions and findings at operation in 30 cases showed high diagnostic accuracy. Conventional, multi-dimensional film tomography is being increasingly replaced by computer tomography.", "contents": "[Computer tomography of the facial skeleton and pharyngeal space (author's transl)]. Seventy-five patients with histologically confirmed abnormalities of the facial skeleton and pharynx, including the mouth and base of the tongue, were examined by computer tomography. The advantages of simultaneous demonstration of the soft tissues and bones in localised space-occupying lesions are pointed out. Accurate comparison between pre-operative descriptions and findings at operation in 30 cases showed high diagnostic accuracy. Conventional, multi-dimensional film tomography is being increasingly replaced by computer tomography."} {"id": "PMID:161258", "title": "[Computer tomographic diagnosis of a mega-dolicho basilar artery (author's transl)].", "content": "Four mega-dolicho basilar arteries are described, which were found by computer tomography and confirmed by angiography. Two patients showed additional abnormalities or anomalies of other vessels. The computer tomographic features are described. The elongated vessels can produce so-called normal pressure hydrocephalus by impressing the floor of the third ventricle, although the hydrocephalus cannot be confirmed by computer tomographic cisternography.", "contents": "[Computer tomographic diagnosis of a mega-dolicho basilar artery (author's transl)]. Four mega-dolicho basilar arteries are described, which were found by computer tomography and confirmed by angiography. Two patients showed additional abnormalities or anomalies of other vessels. The computer tomographic features are described. The elongated vessels can produce so-called normal pressure hydrocephalus by impressing the floor of the third ventricle, although the hydrocephalus cannot be confirmed by computer tomographic cisternography."} {"id": "PMID:161259", "title": "[Roentgenological characteristic of pulmonary metastases in thyroid cancer in respect of its biological behaviour (author's transl)].", "content": "In metastases of the lung which must be considered as typical in cancer of the thyroid, it is possible to differentiate roentgenologically between fine and coarse nodules, the limit being approximately 10 mm. Metastases consisting of fine nodules are by no means to be considered as representing a fatal generalisation, whereas metastases with coarse nodules are frequently accompanied by other metastases distant from the primary tumour.", "contents": "[Roentgenological characteristic of pulmonary metastases in thyroid cancer in respect of its biological behaviour (author's transl)]. In metastases of the lung which must be considered as typical in cancer of the thyroid, it is possible to differentiate roentgenologically between fine and coarse nodules, the limit being approximately 10 mm. Metastases consisting of fine nodules are by no means to be considered as representing a fatal generalisation, whereas metastases with coarse nodules are frequently accompanied by other metastases distant from the primary tumour."} {"id": "PMID:161260", "title": "Doming of the pulmonary valve after valvotomy.", "content": "Doming of the pulmonary valve is considered an important angiographic sign for valvar stenosis. But, this sign cannot be used with similar specificity following valvotomy because at the time of surgery a bicuspid valve is created. Pre- and postoperative hemodynamic data and right ventriculograms are reviewed in 22 patients with simple pulmonary valvar stenosis. There was no correlation between the transvalvar gradient and appearance of the pulmonary valve after surgery.", "contents": "Doming of the pulmonary valve after valvotomy. Doming of the pulmonary valve is considered an important angiographic sign for valvar stenosis. But, this sign cannot be used with similar specificity following valvotomy because at the time of surgery a bicuspid valve is created. Pre- and postoperative hemodynamic data and right ventriculograms are reviewed in 22 patients with simple pulmonary valvar stenosis. There was no correlation between the transvalvar gradient and appearance of the pulmonary valve after surgery."} {"id": "PMID:161261", "title": "[Significance of the contralateral kidney for a successful decrease of blood pressure following renovascular surgery in patients with unilateral renal artery stenosis. Angiographic and pharmacodynamic studies in renovascular and essential hypertension (author's transl)].", "content": "This study was carried out to improve the diagnostic procedure and preoperative prognosis in patients with unilateral renovascular hypertension. The vascular sensitivity of the non-stenosed kidney was tested by the influence on renal hemodynamics (133xenon washout technique) of dihydralazine applicated intrarenally and was correlated with selective renal arteriograms. Comparative studies were done in patients with essential hypertension including those with and without nephrosclerotic lesions. The results demonstrate that the pharmacodynamic effect of the vasodilator used in this study is obtained only in kidneys without arteriosclerotic lesions of the small vessels. A postoperative normalization of blood pressure in patients with unilateral renal artery stenosis depends on a patent renal bypass and a normal vascular response of the contralateral kidney.", "contents": "[Significance of the contralateral kidney for a successful decrease of blood pressure following renovascular surgery in patients with unilateral renal artery stenosis. Angiographic and pharmacodynamic studies in renovascular and essential hypertension (author's transl)]. This study was carried out to improve the diagnostic procedure and preoperative prognosis in patients with unilateral renovascular hypertension. The vascular sensitivity of the non-stenosed kidney was tested by the influence on renal hemodynamics (133xenon washout technique) of dihydralazine applicated intrarenally and was correlated with selective renal arteriograms. Comparative studies were done in patients with essential hypertension including those with and without nephrosclerotic lesions. The results demonstrate that the pharmacodynamic effect of the vasodilator used in this study is obtained only in kidneys without arteriosclerotic lesions of the small vessels. A postoperative normalization of blood pressure in patients with unilateral renal artery stenosis depends on a patent renal bypass and a normal vascular response of the contralateral kidney."} {"id": "PMID:161262", "title": "[Renal blood flow, diuresis and isotope nephrogram in experimental stenosis of the renal artery (author's transl)].", "content": "After experimental stenosis of the renal artery of the dog, the isotope nephrogram shows a prolongation of the transit-time, when the renal blood flow is reduced to 40--70%. This finding was most significant in low diuresis (0,05--0,2 ml/min), sporadic in moderate diuresis (0,2--2,0 ml/min), no longer demonstrable in forced diuresis (greater than 2,0 ml/min). The diuretic effect of X-ray contrast medium (70% Na-Meglumin-Jotalamat, 0,5 ml/kg i.v.) normalizes a pathologic ING in low diuresis.", "contents": "[Renal blood flow, diuresis and isotope nephrogram in experimental stenosis of the renal artery (author's transl)]. After experimental stenosis of the renal artery of the dog, the isotope nephrogram shows a prolongation of the transit-time, when the renal blood flow is reduced to 40--70%. This finding was most significant in low diuresis (0,05--0,2 ml/min), sporadic in moderate diuresis (0,2--2,0 ml/min), no longer demonstrable in forced diuresis (greater than 2,0 ml/min). The diuretic effect of X-ray contrast medium (70% Na-Meglumin-Jotalamat, 0,5 ml/kg i.v.) normalizes a pathologic ING in low diuresis."} {"id": "PMID:161263", "title": "[Pseudo tumours of the adrenals--errors in interpretation and their avoidance (author's transl)].", "content": "In 13 patients an adrenal tumor was suggested by non-invasive roentgenologic studies (scout films of the abdomen, intravenous urograms, tomograms). The lesions turned out to be misdiagnosed after patients had undergone arteriography. Variations of the spleen, superimpositions of the tail of the pancreas and fluid filled hollow viscus were found to be the reason for this adrenal 'pseudo-tumors'. The possibilities of diagnosing those 'lesions' without doing invasive studies are discussed.", "contents": "[Pseudo tumours of the adrenals--errors in interpretation and their avoidance (author's transl)]. In 13 patients an adrenal tumor was suggested by non-invasive roentgenologic studies (scout films of the abdomen, intravenous urograms, tomograms). The lesions turned out to be misdiagnosed after patients had undergone arteriography. Variations of the spleen, superimpositions of the tail of the pancreas and fluid filled hollow viscus were found to be the reason for this adrenal 'pseudo-tumors'. The possibilities of diagnosing those 'lesions' without doing invasive studies are discussed."} {"id": "PMID:161264", "title": "[The lateral projection with an inclined beam for the demonstration of aneurysms of the anterior communicating artery and of the middle cerebral artery (author's transl)].", "content": "In addition to the a.p. and lateral projections for the diagnosis of aneurysms of the anterior communicating artery, the literature also recommends oblique views by turning the head to right or left with an a.p. beam. Lateral views, turning the head 20 degrees to the side of injection often provide better demonstration of the origin of the aneurysm and its relationship to surrounding vessels.", "contents": "[The lateral projection with an inclined beam for the demonstration of aneurysms of the anterior communicating artery and of the middle cerebral artery (author's transl)]. In addition to the a.p. and lateral projections for the diagnosis of aneurysms of the anterior communicating artery, the literature also recommends oblique views by turning the head to right or left with an a.p. beam. Lateral views, turning the head 20 degrees to the side of injection often provide better demonstration of the origin of the aneurysm and its relationship to surrounding vessels."} {"id": "PMID:161265", "title": "[The neuro-radiological anatomy of the normal and abnormal rat brain. I. Radiological techniques for normal anatomy (author's transl)].", "content": "In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment.", "contents": "[The neuro-radiological anatomy of the normal and abnormal rat brain. I. Radiological techniques for normal anatomy (author's transl)]. In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment."} {"id": "PMID:161266", "title": "[Isotope methods in the diagnosis of venous disease. I. Methods of radionuclide venography (author's transl)].", "content": "The method of radionuclide venography is best determined by the localisation and type of suspected venous abnormality. The authors describe four methods using 99mTc microspheres and 99mTc-pertechnetate. Correlation of the isotope and angiographic findings in 150 patients indicated an accuracy of 90% for the isotope methods. The risks of radionuclide venography are discussed. Isotope venography is recommended as a simple, non-invasive technique.", "contents": "[Isotope methods in the diagnosis of venous disease. I. Methods of radionuclide venography (author's transl)]. The method of radionuclide venography is best determined by the localisation and type of suspected venous abnormality. The authors describe four methods using 99mTc microspheres and 99mTc-pertechnetate. Correlation of the isotope and angiographic findings in 150 patients indicated an accuracy of 90% for the isotope methods. The risks of radionuclide venography are discussed. Isotope venography is recommended as a simple, non-invasive technique."} {"id": "PMID:161267", "title": "[Isotope methods in the diagnosis of venous disease. II. Results of radionuclide venography (author's transl)].", "content": "The frequency of scintigraphic findings in the presence of thromboses, post-thrombotic changes and in normal veins, was determined in 150 patients. The results of radionuclide venography and contrast venography in these patients have been compared. Abnormalities in veins can be detected by radionuclide venography with a high degree of accuracy. Differentiation between acute and chronic thrombosis and post-thrombotic changes can only be made by invasive contrast venography.", "contents": "[Isotope methods in the diagnosis of venous disease. II. Results of radionuclide venography (author's transl)]. The frequency of scintigraphic findings in the presence of thromboses, post-thrombotic changes and in normal veins, was determined in 150 patients. The results of radionuclide venography and contrast venography in these patients have been compared. Abnormalities in veins can be detected by radionuclide venography with a high degree of accuracy. Differentiation between acute and chronic thrombosis and post-thrombotic changes can only be made by invasive contrast venography."} {"id": "PMID:161268", "title": "Comparison of monomer, dimer and non-ionized medium at urography with simulated compression; an experimental study in the rabbit [author's transl].", "content": "Density, estimated through renal pelvic volume as calculated according to previous experiments (Owman 1978) and urinary iodine concentration, is suggested to be more accurate than, and complementary to, mere determination of urine iodine concentration and diuresis when evaluating and comparing urographic contrast media experimentally. More reliable dose optima are probably found when calculating density rather than determining urine concentrations. Of the examined media in this investigation, metrizamide and P 268 are by far superior, giving higher density, higher urinary concentrations, and metrizamide also less diuresis.", "contents": "Comparison of monomer, dimer and non-ionized medium at urography with simulated compression; an experimental study in the rabbit [author's transl]. Density, estimated through renal pelvic volume as calculated according to previous experiments (Owman 1978) and urinary iodine concentration, is suggested to be more accurate than, and complementary to, mere determination of urine iodine concentration and diuresis when evaluating and comparing urographic contrast media experimentally. More reliable dose optima are probably found when calculating density rather than determining urine concentrations. Of the examined media in this investigation, metrizamide and P 268 are by far superior, giving higher density, higher urinary concentrations, and metrizamide also less diuresis."} {"id": "PMID:161269", "title": "[A new contrast medium emulsion for lymphography (author's transl)].", "content": "A new contrast medium for lymphography has been developed. It is suitable for direct, such as bi-pedal, lymphangiography, and has certain advantages compared with the commercially available contrast medium Ethiodol, such as absence of a lipogranulomatous reaction and less extensive oil emboli in the lungs. It is also possible to use the substance for indirect, retrosternal lymphography. The substance is indirect, retrosternal lymphography. The substance is an emulsion of triglycerides of iodinated poppy seed oil. The method of preparation of the emulsion is described.", "contents": "[A new contrast medium emulsion for lymphography (author's transl)]. A new contrast medium for lymphography has been developed. It is suitable for direct, such as bi-pedal, lymphangiography, and has certain advantages compared with the commercially available contrast medium Ethiodol, such as absence of a lipogranulomatous reaction and less extensive oil emboli in the lungs. It is also possible to use the substance for indirect, retrosternal lymphography. The substance is indirect, retrosternal lymphography. The substance is an emulsion of triglycerides of iodinated poppy seed oil. The method of preparation of the emulsion is described."} {"id": "PMID:161281", "title": "[The technic of \"open pelviscopy\". A new method for increased safety in laparoscopy].", "content": "The method of \"open pelviscopy\" is described and compared with the common performance of gynecological pelviscopy. The \"open pelviscopy\" combines the advantages of laparotomy--preparation of anatomical layers under view of the operator--with those of pelviscopy--minimal traumatization and optimal view at the intraabdominal organs. This method avoids blind puncture of the abdominal cavity, which otherwise is necessary to perform the pneumoperitoneum and to use the optic instruments. Apart from the well established indications for diagnostic and therapeutic gynecological pelviscopy we prefer this method especially in obese patients and in those who formerly had several laparotomies.", "contents": "[The technic of \"open pelviscopy\". A new method for increased safety in laparoscopy]. The method of \"open pelviscopy\" is described and compared with the common performance of gynecological pelviscopy. The \"open pelviscopy\" combines the advantages of laparotomy--preparation of anatomical layers under view of the operator--with those of pelviscopy--minimal traumatization and optimal view at the intraabdominal organs. This method avoids blind puncture of the abdominal cavity, which otherwise is necessary to perform the pneumoperitoneum and to use the optic instruments. Apart from the well established indications for diagnostic and therapeutic gynecological pelviscopy we prefer this method especially in obese patients and in those who formerly had several laparotomies."} {"id": "PMID:161282", "title": "[The value of laparoscopy in gynecology].", "content": "There is a definite place for laparoscopy in gynaecology as a diagnostic tool and for limited operative procedures. Nevertheless, the indication for laparoscopy should be subjected to the same strict criteria as any other operative procedure. The use of laparoscopy and its various indications are discussed. So-called major operative laparoscopy or pelviscopy is rejected. Greatest restraint should be employed to use laparoscopy for obtaining biopsy material from ovarian tumours for diagnostic purposes.", "contents": "[The value of laparoscopy in gynecology]. There is a definite place for laparoscopy in gynaecology as a diagnostic tool and for limited operative procedures. Nevertheless, the indication for laparoscopy should be subjected to the same strict criteria as any other operative procedure. The use of laparoscopy and its various indications are discussed. So-called major operative laparoscopy or pelviscopy is rejected. Greatest restraint should be employed to use laparoscopy for obtaining biopsy material from ovarian tumours for diagnostic purposes."} {"id": "PMID:161283", "title": "[Necessity of training and safety in gynecological laparoscopy--a contradiction?].", "content": "At the Gynaecological University Hospital G\u00f6ttingen 1659 laparoscopies were performed 1961-1978 by 67 gynaecologists with an average of 24,8 laparoscopies per gynaecologist. Most of the doctors were still in their training period, assistance was always given by a specialist gynaecologist. Only in 5 cases (0,3 per cent) laparotomy was necessary due to complications following laparoscopy or laparoscopicsterilization. Injuries of the transverse colon, the greater omentum and a mesenteric artery-caused by the trocar-were seen, also diffuse bleeding from the parietal peritoneum and from the ramus of the Fallopian tube. No deaths due to laparoscopic complications occurred. The incidence of severe complications can be kept within tolerable limits in a training hospital where the majority of the operations are performed by doctors in training, when the following conditions are strictly adhered to: Careful consideration of the risks involved in laparoscopy/laparoscopic sterilization and other less invasive diagnostic and contraceptive methods, strict attention to the contraindications of laparoscopy and performance of a standardized laparoscopic technique under the supervision of an experienced operateur.", "contents": "[Necessity of training and safety in gynecological laparoscopy--a contradiction?]. At the Gynaecological University Hospital G\u00f6ttingen 1659 laparoscopies were performed 1961-1978 by 67 gynaecologists with an average of 24,8 laparoscopies per gynaecologist. Most of the doctors were still in their training period, assistance was always given by a specialist gynaecologist. Only in 5 cases (0,3 per cent) laparotomy was necessary due to complications following laparoscopy or laparoscopicsterilization. Injuries of the transverse colon, the greater omentum and a mesenteric artery-caused by the trocar-were seen, also diffuse bleeding from the parietal peritoneum and from the ramus of the Fallopian tube. No deaths due to laparoscopic complications occurred. The incidence of severe complications can be kept within tolerable limits in a training hospital where the majority of the operations are performed by doctors in training, when the following conditions are strictly adhered to: Careful consideration of the risks involved in laparoscopy/laparoscopic sterilization and other less invasive diagnostic and contraceptive methods, strict attention to the contraindications of laparoscopy and performance of a standardized laparoscopic technique under the supervision of an experienced operateur."} {"id": "PMID:161285", "title": "Variation in S phase in synchronous human cell lines.", "content": "Growth parameters of diploid and trisomic human fibroblasts were determined. The rate of growth of both classes of cells was examined in asynchronous cultures, and diploid and trisomic cells had similar growth rates. Synchronous cultures were developed using simple mitotic selection. The patterns and length of the DNA synthetic period (S phase) were found to be altered in trisomy 21 cells when compared to diploid human or to heteroploid HeLa cells. Early S-phase synthesis was absent or reduced and the overall length of the S phase was extended. However, the trisomic cells have apparently normal rates of DNA chain elongation and normal replicon sizes.", "contents": "Variation in S phase in synchronous human cell lines. Growth parameters of diploid and trisomic human fibroblasts were determined. The rate of growth of both classes of cells was examined in asynchronous cultures, and diploid and trisomic cells had similar growth rates. Synchronous cultures were developed using simple mitotic selection. The patterns and length of the DNA synthetic period (S phase) were found to be altered in trisomy 21 cells when compared to diploid human or to heteroploid HeLa cells. Early S-phase synthesis was absent or reduced and the overall length of the S phase was extended. However, the trisomic cells have apparently normal rates of DNA chain elongation and normal replicon sizes."} {"id": "PMID:161301", "title": "[Histological differential diagnosis of psoriasis vulgaris and seborrheic eczema of the scalp].", "content": "The clinical differential diagnosis between seborrheic dermatitis and psoriasis vulgaris of the scalp can be difficult. We, therefore, tried to elaborate histopathological criteria for a differentiation of the two dermatoses. Forty excisional biopsies were analysed without knowing the clinical diagnosis. The histopathological substrate within the epidermis is characterized in psoriasis by dermatitis-like and in seborrheic dermatitis by psoriasis-like alterations. Therefore, in some cases a definite histopathological diagnosis could not be made. Strong criteria favouring psoriasis are: moderate condensed hyperkeratosis with alternating parakeratosis, PAS-reactive serum inclusions and Munro abscesses within the horny layer, spongiform pustles and neutrophilic leukocytes within the epidermis. Strong criteria for seborrheic dermatitis are: irregular acanthosis with relatively thin condensed orthoor parakeratotic horny layer, spongiosis and spongiotic vesicles, exocytosis of lymphocytes and the lack of any hard criterias for psoriasis. The results may suggest that seborrheic dermatitis of the scalp may transform into psoriasis in patients with a genetical disposition (\"psoriatic diathesis\", \"latent psoriasis\") via a K\u00f6bner reaction. The existence of the seborrheic dermatitis (Morbus Unna) is not doubted by these investigations.", "contents": "[Histological differential diagnosis of psoriasis vulgaris and seborrheic eczema of the scalp]. The clinical differential diagnosis between seborrheic dermatitis and psoriasis vulgaris of the scalp can be difficult. We, therefore, tried to elaborate histopathological criteria for a differentiation of the two dermatoses. Forty excisional biopsies were analysed without knowing the clinical diagnosis. The histopathological substrate within the epidermis is characterized in psoriasis by dermatitis-like and in seborrheic dermatitis by psoriasis-like alterations. Therefore, in some cases a definite histopathological diagnosis could not be made. Strong criteria favouring psoriasis are: moderate condensed hyperkeratosis with alternating parakeratosis, PAS-reactive serum inclusions and Munro abscesses within the horny layer, spongiform pustles and neutrophilic leukocytes within the epidermis. Strong criteria for seborrheic dermatitis are: irregular acanthosis with relatively thin condensed orthoor parakeratotic horny layer, spongiosis and spongiotic vesicles, exocytosis of lymphocytes and the lack of any hard criterias for psoriasis. The results may suggest that seborrheic dermatitis of the scalp may transform into psoriasis in patients with a genetical disposition (\"psoriatic diathesis\", \"latent psoriasis\") via a K\u00f6bner reaction. The existence of the seborrheic dermatitis (Morbus Unna) is not doubted by these investigations."} {"id": "PMID:161299", "title": "Hemolysis due to aortic insufficiency following closure of ventricular septal defect.", "content": "A two-year-old girl with ventricular septal defect (VSD) developed a severe degree of intravascular hemolysis following VSD closure. The cause of hemolysis was considered to be due to the aortic insufficiency (AI) jet against the VSD patch. The patient was reoperated on the seventh post-operative day. There was a small hole on the right coronary cusp, which was closed by five interrupted sutures. However, a third operation was performed on the following day because of the reappearance of AI. The use of pericardial flap to cover the whole right coronary cusp resulted in disappearance of hemolysis. The patient was discharged in a satisfactory condition.", "contents": "Hemolysis due to aortic insufficiency following closure of ventricular septal defect. A two-year-old girl with ventricular septal defect (VSD) developed a severe degree of intravascular hemolysis following VSD closure. The cause of hemolysis was considered to be due to the aortic insufficiency (AI) jet against the VSD patch. The patient was reoperated on the seventh post-operative day. There was a small hole on the right coronary cusp, which was closed by five interrupted sutures. However, a third operation was performed on the following day because of the reappearance of AI. The use of pericardial flap to cover the whole right coronary cusp resulted in disappearance of hemolysis. The patient was discharged in a satisfactory condition."} {"id": "PMID:161321", "title": "In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication.", "content": "Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates.", "contents": "In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication. Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates."} {"id": "PMID:161322", "title": "Concanavalin A induced suppressor activity in human leprosy.", "content": "Peripheral blood lymphocytes from nine normal subjects and 40 patients with leprosy were pretreated in vitro with Concanavalin A (Con A). Cells from normal subjects pretreated for 24 hours showed consistent and effective generation of suppressive activity which inhibited mitogen induced transformation of autologous lymphocytes. Prolongation of Con A pretreatment to 40 hours resulted in maximal suppressive activity. Tuberculoid leprosy patients had lymphocytes in their blood which on 24 hour pretreatment with Con A exerted suppressive effects markedly greater than the maximal suppression noted with 40 hour pretreated normal lymphocytes. In contrast, untreated patients with polar lepromatous leprosy showed a decrease in suppressive activity which could not be altered by prolongation of Con A pretreatment: the loss of suppressive activity noted in this form of leprosy was restored during erythema nodosum leprosum.", "contents": "Concanavalin A induced suppressor activity in human leprosy. Peripheral blood lymphocytes from nine normal subjects and 40 patients with leprosy were pretreated in vitro with Concanavalin A (Con A). Cells from normal subjects pretreated for 24 hours showed consistent and effective generation of suppressive activity which inhibited mitogen induced transformation of autologous lymphocytes. Prolongation of Con A pretreatment to 40 hours resulted in maximal suppressive activity. Tuberculoid leprosy patients had lymphocytes in their blood which on 24 hour pretreatment with Con A exerted suppressive effects markedly greater than the maximal suppression noted with 40 hour pretreated normal lymphocytes. In contrast, untreated patients with polar lepromatous leprosy showed a decrease in suppressive activity which could not be altered by prolongation of Con A pretreatment: the loss of suppressive activity noted in this form of leprosy was restored during erythema nodosum leprosum."} {"id": "PMID:161324", "title": "Attraction to \"good form\" in Down's syndrome.", "content": "Seventy-five children were examined in tasks involving matching figures in order to establish whether there exists a specific attraction to symmetrical or Gestalt type \"good form\" displays in mentally handicapped children and particularly in Down's Syndrome or if the tendency was towards image reversal. Twenty-five children with Down's Syndrome were matched on M.A. with twenty-five non-Down's Syndrome subnormals and twenty-five normal children. Symmetrical and asymmetrical displays were presented to the groups for reproduction and reproduction from memory. The results supported the hypothesis that mentally handicapped children have a significant attraction to symmetrical arrangements and that Down's Syndrome children are more significantly attracted than other handicapped children. Evidence is presented to show that what often is mistaken for a tendency to image reversal is in fact an attraction to \"monotonicity\" and is more related to \"good form\" than to reversal.", "contents": "Attraction to \"good form\" in Down's syndrome. Seventy-five children were examined in tasks involving matching figures in order to establish whether there exists a specific attraction to symmetrical or Gestalt type \"good form\" displays in mentally handicapped children and particularly in Down's Syndrome or if the tendency was towards image reversal. Twenty-five children with Down's Syndrome were matched on M.A. with twenty-five non-Down's Syndrome subnormals and twenty-five normal children. Symmetrical and asymmetrical displays were presented to the groups for reproduction and reproduction from memory. The results supported the hypothesis that mentally handicapped children have a significant attraction to symmetrical arrangements and that Down's Syndrome children are more significantly attracted than other handicapped children. Evidence is presented to show that what often is mistaken for a tendency to image reversal is in fact an attraction to \"monotonicity\" and is more related to \"good form\" than to reversal."} {"id": "PMID:161325", "title": "Dermatoglyphic distances and position of 21 trisomy mosaics.", "content": "The position of 21 trisomy mosaics with an average proportion of trisomic cells approximating 0.5 in relation to normal subjects and those with complete 21 trisomy has been evaluated by means of dermatoglyphic distances, using samples of 142 mosaics, 302 normal controls and 225 complete 21 trisomics for males and females separately and combined. Distances were calculated by means of the simplified D2k method. Penrose's \"size and shape\" analysis of variance has been applied for comparison to obtain distance coefficients, C2H, based on pattern intensities. Results indicate that mosaics are not intermediate but much closer to 21 trisomics in spite of the fact that the average proportion of trisomic cells in blood approximates 0.5; secondly, that the degree of deviation from the intermediate position of the mosaic sample is roughly proportional to the degree of cytological mosaicism. The position of mosaics is appreciably more intermediate in respect of finger-tip patterns than in respect of palmar and sole loops and triradii. The results obtained here have thus given evidence for the usefulness of dermatoglyphic distances, which enable all the differences in frequencies or means of the respective characters to be conveniently represented by a single number, in studies of the abnormal development of phenotypic characteristics in cases of incomplete trisomy.", "contents": "Dermatoglyphic distances and position of 21 trisomy mosaics. The position of 21 trisomy mosaics with an average proportion of trisomic cells approximating 0.5 in relation to normal subjects and those with complete 21 trisomy has been evaluated by means of dermatoglyphic distances, using samples of 142 mosaics, 302 normal controls and 225 complete 21 trisomics for males and females separately and combined. Distances were calculated by means of the simplified D2k method. Penrose's \"size and shape\" analysis of variance has been applied for comparison to obtain distance coefficients, C2H, based on pattern intensities. Results indicate that mosaics are not intermediate but much closer to 21 trisomics in spite of the fact that the average proportion of trisomic cells in blood approximates 0.5; secondly, that the degree of deviation from the intermediate position of the mosaic sample is roughly proportional to the degree of cytological mosaicism. The position of mosaics is appreciably more intermediate in respect of finger-tip patterns than in respect of palmar and sole loops and triradii. The results obtained here have thus given evidence for the usefulness of dermatoglyphic distances, which enable all the differences in frequencies or means of the respective characters to be conveniently represented by a single number, in studies of the abnormal development of phenotypic characteristics in cases of incomplete trisomy."} {"id": "PMID:161326", "title": "Some characteristics of a population of mentally retarded young adults in a British city. A basis for estimating some service needs.", "content": "A population of young people who are mentally retarded is described in terms of the frequency of various kinds and degrees of impairment--intellectual, physical and behavioural. The population consisted of all those born in 1951--1955 who were resident in a city in 1962 and who at any time during the school years had been placed in any mental retardation service. The prevalence of the mentally retarded as defined is sixteen per 1000. Age specific prevalence rates for the same population rise from age five, reach a plateau of fourteen per 1000 from ages ten to fifteen and then drop sharply for the post-school period to a rate of five to six per 1000. Classifications of physical impairment, seizure histories and behaviour disturbances are described. Percentages are given separately for those with each impairment and in combination for each individual. For the survivors at age twenty-two, 44 per cent had physical impairments, 26 per cent had a history of seizures and 46 per cent had experienced behaviour disturbances. Results are discussed in relation to service needs.", "contents": "Some characteristics of a population of mentally retarded young adults in a British city. A basis for estimating some service needs. A population of young people who are mentally retarded is described in terms of the frequency of various kinds and degrees of impairment--intellectual, physical and behavioural. The population consisted of all those born in 1951--1955 who were resident in a city in 1962 and who at any time during the school years had been placed in any mental retardation service. The prevalence of the mentally retarded as defined is sixteen per 1000. Age specific prevalence rates for the same population rise from age five, reach a plateau of fourteen per 1000 from ages ten to fifteen and then drop sharply for the post-school period to a rate of five to six per 1000. Classifications of physical impairment, seizure histories and behaviour disturbances are described. Percentages are given separately for those with each impairment and in combination for each individual. For the survivors at age twenty-two, 44 per cent had physical impairments, 26 per cent had a history of seizures and 46 per cent had experienced behaviour disturbances. Results are discussed in relation to service needs."} {"id": "PMID:161327", "title": "Kinaesthetic movement after-effects in children with Down's syndrome.", "content": "In order to assess the liability of proprioceptive information, an experiment on kinaesthetic after-effects was carried out. Matched groups of severely subnormal and Down's syndrome subjects were compared with normal children of either the same chronological or the same mental age. No difference was found between the normal and the severely subnormal children, but the magnitude of the after-effect measures in Down's syndrome children suggests that asymmetrical pointing produced kinaesthetic after-effects which disrupted these subjects' total frame of spatial reference.", "contents": "Kinaesthetic movement after-effects in children with Down's syndrome. In order to assess the liability of proprioceptive information, an experiment on kinaesthetic after-effects was carried out. Matched groups of severely subnormal and Down's syndrome subjects were compared with normal children of either the same chronological or the same mental age. No difference was found between the normal and the severely subnormal children, but the magnitude of the after-effect measures in Down's syndrome children suggests that asymmetrical pointing produced kinaesthetic after-effects which disrupted these subjects' total frame of spatial reference."} {"id": "PMID:161333", "title": "[Health effects of trichloroethylene in human subjects (author's transl)].", "content": "Trichloroethylene has been widely used for the removal of grease in dry cleaning, plate and painting industries, in which approximately 280 thousand workers contact trichloroethylene, for example, in the United States, resulting in acute and chronic poisonings. Based on 203 papers mainly on trichloroethylene toxicity on human beings, the present review covers acute toxicity, chronic toxicity, carcinogenicity, factors modifying toxicity, metabolism, dose-response relationships and maximum allowable concentration of this chemical. 1 figure and 12 tables.", "contents": "[Health effects of trichloroethylene in human subjects (author's transl)]. Trichloroethylene has been widely used for the removal of grease in dry cleaning, plate and painting industries, in which approximately 280 thousand workers contact trichloroethylene, for example, in the United States, resulting in acute and chronic poisonings. Based on 203 papers mainly on trichloroethylene toxicity on human beings, the present review covers acute toxicity, chronic toxicity, carcinogenicity, factors modifying toxicity, metabolism, dose-response relationships and maximum allowable concentration of this chemical. 1 figure and 12 tables."} {"id": "PMID:161335", "title": "Role of brain amines in the fetal hyperpyrexia caused by tranylcypromine in LiCl-pretreated rats.", "content": "Tranylcypromine (TCP), a monoamine oxidase inhibitor, caused a fatal hyperpyrexia in rats pretreated with LiCl once a day for 4 days. Pretreatment with LiCl alone did not alter the level of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) in the brain. In fatal hyperpyrexia caused by LiCl plus TCP, the brain 5-HT and DA levels were increased, whereas the brain NE level was decreased. Reserpine and alpha-methyl-p-tyrosine completely prevented the hyperpyrexia, but FLA-63 did not show any effect. The hyperpyrexia was completely prevented by p-chlorophenylalanine (PCPA) given 72 hours before TCP but not by PCPA given 24 hours before TCP. Haloperidol and chlorpromazine, DA receptor blockers, inhibited the fatal hyperpyrexia, while cyproheptadine and methysergide, 5-HT receptor blockers, did not. These results suggest that DA plays an essential role in the hyperpyrexia induced by the combination of TCP and LiCl in rats, but the involvement of 5-HT is inconclusive.", "contents": "Role of brain amines in the fetal hyperpyrexia caused by tranylcypromine in LiCl-pretreated rats. Tranylcypromine (TCP), a monoamine oxidase inhibitor, caused a fatal hyperpyrexia in rats pretreated with LiCl once a day for 4 days. Pretreatment with LiCl alone did not alter the level of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) in the brain. In fatal hyperpyrexia caused by LiCl plus TCP, the brain 5-HT and DA levels were increased, whereas the brain NE level was decreased. Reserpine and alpha-methyl-p-tyrosine completely prevented the hyperpyrexia, but FLA-63 did not show any effect. The hyperpyrexia was completely prevented by p-chlorophenylalanine (PCPA) given 72 hours before TCP but not by PCPA given 24 hours before TCP. Haloperidol and chlorpromazine, DA receptor blockers, inhibited the fatal hyperpyrexia, while cyproheptadine and methysergide, 5-HT receptor blockers, did not. These results suggest that DA plays an essential role in the hyperpyrexia induced by the combination of TCP and LiCl in rats, but the involvement of 5-HT is inconclusive."} {"id": "PMID:161336", "title": "Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidoethyl nitrate (SG-75).", "content": "The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.", "contents": "Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidoethyl nitrate (SG-75). The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors."} {"id": "PMID:161337", "title": "Transport of dextran sulfates to rat livers.", "content": "Liver subcellular distributions of three different dextran sulfates (DSs) with average molecular weight (AMW) of 3000, 20,000, and 200,000, and sulfur content of 18%, anticoagulants and antilipemic agents, were examined in rats after intravenous administration of 50 mg/kg. About 20% of the injected radioactivity was taken up by liver 15 min-3 hr after 35S-DS administration, but the uptake of 35S-DS with AMW of 200,000 was slower than that of the other DSs. About half of the radioactivity distributed in livers was found in the cytosol fraction. The cytosol fraction/liver ratio of the radioactivity gradually decreased with the increase in the nuclear fraction/liver ratio. The specific radioactivity of the lysosomal fraction was 5--20 times as large as that of the other fractions. Unchanged forms of 35S-DSs with AMW of 3000 and 20,000 were found in the lysosomal and the cytosol fractions. Administration of DSs with AMW of 20,000 and 200,000 significantly enhanced the Na+-K+-dependent ATPase activity of lysosomal fraction which has been considered to be an index of endocytosis. These findings suggest that DSs are probably transferred into liver cells by transmembrane and endocytotic transports.", "contents": "Transport of dextran sulfates to rat livers. Liver subcellular distributions of three different dextran sulfates (DSs) with average molecular weight (AMW) of 3000, 20,000, and 200,000, and sulfur content of 18%, anticoagulants and antilipemic agents, were examined in rats after intravenous administration of 50 mg/kg. About 20% of the injected radioactivity was taken up by liver 15 min-3 hr after 35S-DS administration, but the uptake of 35S-DS with AMW of 200,000 was slower than that of the other DSs. About half of the radioactivity distributed in livers was found in the cytosol fraction. The cytosol fraction/liver ratio of the radioactivity gradually decreased with the increase in the nuclear fraction/liver ratio. The specific radioactivity of the lysosomal fraction was 5--20 times as large as that of the other fractions. Unchanged forms of 35S-DSs with AMW of 3000 and 20,000 were found in the lysosomal and the cytosol fractions. Administration of DSs with AMW of 20,000 and 200,000 significantly enhanced the Na+-K+-dependent ATPase activity of lysosomal fraction which has been considered to be an index of endocytosis. These findings suggest that DSs are probably transferred into liver cells by transmembrane and endocytotic transports."} {"id": "PMID:161338", "title": "Effect of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the immediate and delayed hypersensitivity reactions.", "content": "Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complete-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.", "contents": "Effect of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the immediate and delayed hypersensitivity reactions. Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complete-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction."} {"id": "PMID:161341", "title": "Use of a gait abnormality index for locomotion efficiency evaluation.", "content": "A number of gait curves obtained from 16 healthy, able-bodied adult males were selected as \"normal\" gait curves and thereafter analysed with a view to defining a \"Gait Abnormality Index\", which may be used as quantitative measure of human performance in locomotion. Similar studies on five groups of handicapped subjects, each group having 8 to 10 subjects with a particular type of handicap, indicate the suitability of this index for application in locomotion efficiency evaluation.", "contents": "Use of a gait abnormality index for locomotion efficiency evaluation. A number of gait curves obtained from 16 healthy, able-bodied adult males were selected as \"normal\" gait curves and thereafter analysed with a view to defining a \"Gait Abnormality Index\", which may be used as quantitative measure of human performance in locomotion. Similar studies on five groups of handicapped subjects, each group having 8 to 10 subjects with a particular type of handicap, indicate the suitability of this index for application in locomotion efficiency evaluation."} {"id": "PMID:161343", "title": "W reactivation is inefficient in repair of the bacterial chromosome.", "content": "UV-inducible \"SOS\" processes associated with W reactivation of phage lambda were studied for their effect on repair of lambda prophage integrated in the bacterial chromosome. For this purpose, lambda c1857 ind red-lysogens were used. These lysogens, although non-inducible by UV light, can be induced by raising the temperature from 30 degrees to 42 degrees. If the W reactivation processes are involved in repair of the bacterial DNA, when the lysogens are incubated at 30 degrees after UV exposure W reactivation should be fully expressed and should also exert an effect on the bacterial chromosome and the prophage inside it. When heat-induction is delayed until the time at which W reactivation reaches its maximum, a considerable increase in phage survival might then be expected. The results presented in this report show, however, that the delayed induction had only a small effect on the survival of prophage in the wild-type strain (possibly attributable to excision repair) and no detectable effect on prophage in a uvrA strain. From these results we conclude that W reactivation is largely irrelevant to the repair of UV-damaged bacterial DNA.", "contents": "W reactivation is inefficient in repair of the bacterial chromosome. UV-inducible \"SOS\" processes associated with W reactivation of phage lambda were studied for their effect on repair of lambda prophage integrated in the bacterial chromosome. For this purpose, lambda c1857 ind red-lysogens were used. These lysogens, although non-inducible by UV light, can be induced by raising the temperature from 30 degrees to 42 degrees. If the W reactivation processes are involved in repair of the bacterial DNA, when the lysogens are incubated at 30 degrees after UV exposure W reactivation should be fully expressed and should also exert an effect on the bacterial chromosome and the prophage inside it. When heat-induction is delayed until the time at which W reactivation reaches its maximum, a considerable increase in phage survival might then be expected. The results presented in this report show, however, that the delayed induction had only a small effect on the survival of prophage in the wild-type strain (possibly attributable to excision repair) and no detectable effect on prophage in a uvrA strain. From these results we conclude that W reactivation is largely irrelevant to the repair of UV-damaged bacterial DNA."} {"id": "PMID:161345", "title": "Diets deficient in copper and zinc?", "content": "Hospital diets, and, perhaps, diets in general may be low in copper and zinc, with the diets being lower in copper than zinc in comparison to requirements. Several human diseases or pathologic conditions of unknown etiology have similarities to findings in deficient animals. Thus nutritional status and metabolism of copper may be important in anemia, ischemic heart disease, rheumatoid arthritis, osteoporosis, multiple sclerosis and seborrheic dermatitis. Zinc may be involved in growth failure, acne, difficulties of labor, congenital abnormalities and wound healing. Whether or not dietary amounts of copper and zinc are involved in the etiology or the pathogenesis of these conditions can be determined by clinical investigation.", "contents": "Diets deficient in copper and zinc? Hospital diets, and, perhaps, diets in general may be low in copper and zinc, with the diets being lower in copper than zinc in comparison to requirements. Several human diseases or pathologic conditions of unknown etiology have similarities to findings in deficient animals. Thus nutritional status and metabolism of copper may be important in anemia, ischemic heart disease, rheumatoid arthritis, osteoporosis, multiple sclerosis and seborrheic dermatitis. Zinc may be involved in growth failure, acne, difficulties of labor, congenital abnormalities and wound healing. Whether or not dietary amounts of copper and zinc are involved in the etiology or the pathogenesis of these conditions can be determined by clinical investigation."} {"id": "PMID:161346", "title": "Occipitofrontal-biparietal diameter ratio. An ultrasonic parameter for the antenatal evaluation of Down's syndrome.", "content": "The cephalic index of the fetal head was determined by the ultrasonic measurement of the occipitofrontal-biparietal diameter (OF-BPD) ratio in a pilot study of 53 patients at risk of Down's syndrome. The mean value of the OF-BPD ratio was 1.24, and a linear correlation between the occipitofrontal diameter (OFD) and the biparietal diameter (BPD) was observed. There was one case of Down's syndrome in this series. The fetal head was markedly brachycephalic with an OF-BPD ratio of 1.073. The results of this study suggest that when fetal brachycephaly is present, the probability of Down's syndrome is increased. Further evaluation of this parameter is warranted, as it is possible that this technique may provide a safe, and non-invasive method of screening the entire pregnant population for Down's syndrome.", "contents": "Occipitofrontal-biparietal diameter ratio. An ultrasonic parameter for the antenatal evaluation of Down's syndrome. The cephalic index of the fetal head was determined by the ultrasonic measurement of the occipitofrontal-biparietal diameter (OF-BPD) ratio in a pilot study of 53 patients at risk of Down's syndrome. The mean value of the OF-BPD ratio was 1.24, and a linear correlation between the occipitofrontal diameter (OFD) and the biparietal diameter (BPD) was observed. There was one case of Down's syndrome in this series. The fetal head was markedly brachycephalic with an OF-BPD ratio of 1.073. The results of this study suggest that when fetal brachycephaly is present, the probability of Down's syndrome is increased. Further evaluation of this parameter is warranted, as it is possible that this technique may provide a safe, and non-invasive method of screening the entire pregnant population for Down's syndrome."} {"id": "PMID:161348", "title": "[Treatment of obstructive disease with fenoterol-ipratropiumbromid dosage aerosol (IK 6). Short and long-terms results (author's transl)].", "content": "Fenoterol-Ipratropiumbromid dosage aerosol (IK 6) showed in acute experiments on patients with chronic obstructive disease optimal bronchodilatation. In this mixture of Fenoterol and Ipratropiumbromid only 50% of the optimal dosage of the beta 2-stimulator is present. This minimizes the side-effects and increases the therapeutic range. Still the bronchodilatation is optimal. 92 patients were treated with this mixture for between 1 and 160 months. No side-effects were seen. The optimal bronchodilatatoric effect was always present.", "contents": "[Treatment of obstructive disease with fenoterol-ipratropiumbromid dosage aerosol (IK 6). Short and long-terms results (author's transl)]. Fenoterol-Ipratropiumbromid dosage aerosol (IK 6) showed in acute experiments on patients with chronic obstructive disease optimal bronchodilatation. In this mixture of Fenoterol and Ipratropiumbromid only 50% of the optimal dosage of the beta 2-stimulator is present. This minimizes the side-effects and increases the therapeutic range. Still the bronchodilatation is optimal. 92 patients were treated with this mixture for between 1 and 160 months. No side-effects were seen. The optimal bronchodilatatoric effect was always present."} {"id": "PMID:161399", "title": "Isolation of a genomal clone containing chicken histone genes.", "content": "We have used enriched chicken histone cDNA to select genomal clones from a chicken library. Because the cDNA probe also contained other sequences, a further screening of positive plagues with negative probes eliminated most non-histone gene clones. One 'positively-selected' genomal clone, lambda CH-01, hybridised with cloned sea-urchin histone genes and also detected histone genes in EcoRI-digested genomal sea-urchin DNA. Limited DNA sequencing of HaeIII fragments identified two sequences within the coding region of chicken histone H2A. A third fragment predicted an amino acid sequence with strong homology to an H1 histone sequence.", "contents": "Isolation of a genomal clone containing chicken histone genes. We have used enriched chicken histone cDNA to select genomal clones from a chicken library. Because the cDNA probe also contained other sequences, a further screening of positive plagues with negative probes eliminated most non-histone gene clones. One 'positively-selected' genomal clone, lambda CH-01, hybridised with cloned sea-urchin histone genes and also detected histone genes in EcoRI-digested genomal sea-urchin DNA. Limited DNA sequencing of HaeIII fragments identified two sequences within the coding region of chicken histone H2A. A third fragment predicted an amino acid sequence with strong homology to an H1 histone sequence."} {"id": "PMID:161401", "title": "PCPA potentiates the effects of specific copulatory experience on the sexual behavior of the pudendectomized male rat.", "content": "The interactional effects of bilateral pudendectomy and sexual experience were studied on the sexual behavior of male rats. In Experiment 1, limited sexual experience in terms of mounts, intromissions or ejaculations was provided prior to the operation. The sexual behavior was then tested before and after treatment with PCPA, a drug known to increase the sexual activity of male rats. In Experiment 2, massive sexual experience was provided the animals prior to pudendectomy, and the sexual behavior was tested with or without PCPA treatment. No variety of limited sexual experience differentiated the effects of pudendectomy. After PCPA treatment, however, the intromittive and ejaculatory capacity of all experienced animals improved significantly. In animals with massive sexual experience the behavioral dysfunctions after pudendectomy were even more dramatically counteracted by PCPA treatment.", "contents": "PCPA potentiates the effects of specific copulatory experience on the sexual behavior of the pudendectomized male rat. The interactional effects of bilateral pudendectomy and sexual experience were studied on the sexual behavior of male rats. In Experiment 1, limited sexual experience in terms of mounts, intromissions or ejaculations was provided prior to the operation. The sexual behavior was then tested before and after treatment with PCPA, a drug known to increase the sexual activity of male rats. In Experiment 2, massive sexual experience was provided the animals prior to pudendectomy, and the sexual behavior was tested with or without PCPA treatment. No variety of limited sexual experience differentiated the effects of pudendectomy. After PCPA treatment, however, the intromittive and ejaculatory capacity of all experienced animals improved significantly. In animals with massive sexual experience the behavioral dysfunctions after pudendectomy were even more dramatically counteracted by PCPA treatment."} {"id": "PMID:161402", "title": "Interaction of actin with myosin A and heavy meromyosin.", "content": "Ca2+ \"free\" actomyosin suspensions as well as actin heavy meromyosin (HMM) solutions in the presence of Ca2+ showed no contractile response (superprecipitation) and had low steady-state Mg2+-ATPase activity. Under the same experimental conditions both the enzymatic activity increased and contractile response was restored if the solubility of the proteins was depressed by the addition of polyethylene glycol 4000 (PEG-4000). The stability of the enzymatically active actomyosin or actin HMM complexes was 10 times lower in cleared solutions than in the insoluble actomyosin or actin HMM suspensions. It was concluded that soluble actomyosin or actin HMM solutions are inadequate test tube models for studying muscular contraction.", "contents": "Interaction of actin with myosin A and heavy meromyosin. Ca2+ \"free\" actomyosin suspensions as well as actin heavy meromyosin (HMM) solutions in the presence of Ca2+ showed no contractile response (superprecipitation) and had low steady-state Mg2+-ATPase activity. Under the same experimental conditions both the enzymatic activity increased and contractile response was restored if the solubility of the proteins was depressed by the addition of polyethylene glycol 4000 (PEG-4000). The stability of the enzymatically active actomyosin or actin HMM complexes was 10 times lower in cleared solutions than in the insoluble actomyosin or actin HMM suspensions. It was concluded that soluble actomyosin or actin HMM solutions are inadequate test tube models for studying muscular contraction."} {"id": "PMID:161403", "title": "[Serious side effects with D-penicillamine therapy for Wilson's disease].", "content": "Immunocomplex nephritis as one of the serious side-effects is dealt with on the basis of 41 patients with Wilson's Disease who have been treated for many years and were stabilised on D-penicillinamine. In one quarter of the patients, proteinuria was found 1 to 5 years after the beginning of the therapy. Until now, an immunocomplex nephritis with diffuse granular, mainly epimembranous IgG and C3 deposits on the glomerular basement membran was found in four patients. No circulating antibodies against cell nuclei were found. The finding of immunocomplex nephritis calls for the discontinuation of the therapy for an at present unknown period of time.", "contents": "[Serious side effects with D-penicillamine therapy for Wilson's disease]. Immunocomplex nephritis as one of the serious side-effects is dealt with on the basis of 41 patients with Wilson's Disease who have been treated for many years and were stabilised on D-penicillinamine. In one quarter of the patients, proteinuria was found 1 to 5 years after the beginning of the therapy. Until now, an immunocomplex nephritis with diffuse granular, mainly epimembranous IgG and C3 deposits on the glomerular basement membran was found in four patients. No circulating antibodies against cell nuclei were found. The finding of immunocomplex nephritis calls for the discontinuation of the therapy for an at present unknown period of time."} {"id": "PMID:161404", "title": "Demographic and affective covariates of pain.", "content": "Relationships of four demographic variables and five affective variables to eight attributes of low back pain were investigated in 251 patients by stepwise, multivariate analysis. The demographic variables are age, sex, race, and education. The affective variables are state anxiety, trait anxiety anxiety, hostility, and depression. Seven of the pain variables are from the factorially derived Low Back Pain Questionnaire. The eighth pain variable is a self-estimate of intensity. Relationships among demographic and pain variables are small and unsystematic. Hostility has a small, systematically inverse relation to pain variables, supporting theories relating low back pain to inhibition of anger. Anxiety has a small positive relationship, and depression has no relationship to pain variables. In general, the small relationships indicate that the Low Back Pain Questionnaire provides descriptions of pain that are not confounded by social characteristics or current emotional states of patients.", "contents": "Demographic and affective covariates of pain. Relationships of four demographic variables and five affective variables to eight attributes of low back pain were investigated in 251 patients by stepwise, multivariate analysis. The demographic variables are age, sex, race, and education. The affective variables are state anxiety, trait anxiety anxiety, hostility, and depression. Seven of the pain variables are from the factorially derived Low Back Pain Questionnaire. The eighth pain variable is a self-estimate of intensity. Relationships among demographic and pain variables are small and unsystematic. Hostility has a small, systematically inverse relation to pain variables, supporting theories relating low back pain to inhibition of anger. Anxiety has a small positive relationship, and depression has no relationship to pain variables. In general, the small relationships indicate that the Low Back Pain Questionnaire provides descriptions of pain that are not confounded by social characteristics or current emotional states of patients."} {"id": "PMID:161408", "title": "[Subjective causal explanation models in the process of coping with a physical impairment (author's transl)].", "content": "The article points out to what extent subjective cognitions and, in particular, na\u00efve explanation models can influence the process of adjustment to the functional limitations of person afflicted with a permanent or long-lasting impairment of his physical integrity. Examples of persons with fairly different types of impairments indicate that in such cases, individual explanation models must always be assumed. This is all the more important because these models can considerably hamper rehabilitation and preventive procedures as a result of their influence on personal experience and behaviour. On the basis of these statements the article points out the necessity of taking the psychological situation of the individual still more into account within the overall treatment.", "contents": "[Subjective causal explanation models in the process of coping with a physical impairment (author's transl)]. The article points out to what extent subjective cognitions and, in particular, na\u00efve explanation models can influence the process of adjustment to the functional limitations of person afflicted with a permanent or long-lasting impairment of his physical integrity. Examples of persons with fairly different types of impairments indicate that in such cases, individual explanation models must always be assumed. This is all the more important because these models can considerably hamper rehabilitation and preventive procedures as a result of their influence on personal experience and behaviour. On the basis of these statements the article points out the necessity of taking the psychological situation of the individual still more into account within the overall treatment."} {"id": "PMID:161409", "title": "[The severely disabled: a new way of driving a car (author's transl)].", "content": "In many cases, the provision of an automobile equipped with a special control system is a necessary part of the rehabilitation of the severely disabled. The car is so important to the disabled as it enables him to overcome daily the distance between home and place of work, hence increasing his mobility and life quality. The presented care control system was developed to meet the individual needs of a particular disability. It is, however, possible to use this system for, or adapt it to, similar types of disabilities. This problem complex has been overcome by following innovations: 1. The electronically controlled accelerator which can be operated with minimal finger pressure. 2. The LIDA shoulder device for tetraplegics, a connecting piece between the shoulder and the manually operated brake lever. 3. The removable armrest on the right hand side of the driver's seat to improve the sitting stability. The car can be easily be converted for \"normal driving\". The author received financial assistance.", "contents": "[The severely disabled: a new way of driving a car (author's transl)]. In many cases, the provision of an automobile equipped with a special control system is a necessary part of the rehabilitation of the severely disabled. The car is so important to the disabled as it enables him to overcome daily the distance between home and place of work, hence increasing his mobility and life quality. The presented care control system was developed to meet the individual needs of a particular disability. It is, however, possible to use this system for, or adapt it to, similar types of disabilities. This problem complex has been overcome by following innovations: 1. The electronically controlled accelerator which can be operated with minimal finger pressure. 2. The LIDA shoulder device for tetraplegics, a connecting piece between the shoulder and the manually operated brake lever. 3. The removable armrest on the right hand side of the driver's seat to improve the sitting stability. The car can be easily be converted for \"normal driving\". The author received financial assistance."} {"id": "PMID:161410", "title": "Immunological release of histamine from human lung. II. Studies on acetylcholine and the anticholinergic agent ipratropium bromide.", "content": "The experiments reported in this work have been performed to measure the effects of acetylcholine and the anticholinergic agent ipratropium bromide on the antigen-induced release of histamine from sensitized human lung in vitro. Primarily, ipratropium bromide did not have any effect, even at higher concentrations. Acetylcholine at a concentration of 1 x 10(-7)M increased the antigen-induced release of histamine by approximately 41%. When the lung tissue was treated with ipratropium bromide before acetylcholine, the competitive inhibition of the cholinergic receptor almost completely abolished this acetylcholine-induced increase of histamine release. Therefore, in our opinion, anticholinergic agents are primarily useful in vagus-controlled chronic obstructive ventilatory disorders; they are of secondary importance in allergic bronchial asthma.", "contents": "Immunological release of histamine from human lung. II. Studies on acetylcholine and the anticholinergic agent ipratropium bromide. The experiments reported in this work have been performed to measure the effects of acetylcholine and the anticholinergic agent ipratropium bromide on the antigen-induced release of histamine from sensitized human lung in vitro. Primarily, ipratropium bromide did not have any effect, even at higher concentrations. Acetylcholine at a concentration of 1 x 10(-7)M increased the antigen-induced release of histamine by approximately 41%. When the lung tissue was treated with ipratropium bromide before acetylcholine, the competitive inhibition of the cholinergic receptor almost completely abolished this acetylcholine-induced increase of histamine release. Therefore, in our opinion, anticholinergic agents are primarily useful in vagus-controlled chronic obstructive ventilatory disorders; they are of secondary importance in allergic bronchial asthma."} {"id": "PMID:161406", "title": "[Plant extracts with cytostatic properties growing in Cuba. II].", "content": "The study of the cytostatic activity of aqueous, alcoholic and ketonic extracts from 18 parts of 9 species of superior plants of the families Araceae, Borraginacease, Burseraceae, Cesalpinaceae, Meliaceae, Compositae, Rebiaceae, Cruciferaceae and Verbenaceae using the microbiologic method of described by Kubas in 1972 is pursued. The best results were obtained from Hamelia patens. Lippia alba, Lepidium virginicum, Cassia ligustrina, Bursera simaruba and Heliotropium campechianum extracts.", "contents": "[Plant extracts with cytostatic properties growing in Cuba. II]. The study of the cytostatic activity of aqueous, alcoholic and ketonic extracts from 18 parts of 9 species of superior plants of the families Araceae, Borraginacease, Burseraceae, Cesalpinaceae, Meliaceae, Compositae, Rebiaceae, Cruciferaceae and Verbenaceae using the microbiologic method of described by Kubas in 1972 is pursued. The best results were obtained from Hamelia patens. Lippia alba, Lepidium virginicum, Cassia ligustrina, Bursera simaruba and Heliotropium campechianum extracts."} {"id": "PMID:161407", "title": "[Plant extracts with cytostatic properties growing in Cuba. I].", "content": "The cytostatic activity of aqueous, alcoholic and ketonic extracts of 9 species of superior plants of the families Fitolacaceae, Compositae, Moraceae, Zingiberaceae, Martiniaceae, Mirtaceae, Verbenaceae and Annonaceae was assessed. The Kubas microbiologic method and the fungus Ascomiceto Neurospora crassa were used in the assessment. The fungus growth was measured in millimeters. Inhibition percentages for every case regarding control are reported. The best results were obtained from Annona muricata, Costus spiralis, Cecropia peltata, Xanthium chinense and Pluchea adorata extracts.", "contents": "[Plant extracts with cytostatic properties growing in Cuba. I]. The cytostatic activity of aqueous, alcoholic and ketonic extracts of 9 species of superior plants of the families Fitolacaceae, Compositae, Moraceae, Zingiberaceae, Martiniaceae, Mirtaceae, Verbenaceae and Annonaceae was assessed. The Kubas microbiologic method and the fungus Ascomiceto Neurospora crassa were used in the assessment. The fungus growth was measured in millimeters. Inhibition percentages for every case regarding control are reported. The best results were obtained from Annona muricata, Costus spiralis, Cecropia peltata, Xanthium chinense and Pluchea adorata extracts."} {"id": "PMID:161414", "title": "[Side effects of oral retinoid Ro 10-9359 on the unaffected skin of psoriatic patients: retinoid dermatitis].", "content": "Dermatitis occurring as a side effect in psoriatic patients during oral administration of the retinoid acid derivative Ro 10-9359 is described. This so-called retinoid dermatitis exhibits a characteristic disseminated pattern. Sites of predilection are the face, the exterior surface of the upper and the interior surface of the lower arms, the superior thoracic aperture, the back of the hands and the flanks. The lesions present as follicular papules and/or vesicles. The histological picture is that of acute non-specific dermatitis. This retinoid dermatitis was observed in 9 our of 23 patients (39%) treated with Ro 10-9359. Other side effect such as erythema, desquamation, itching and, rarely, a burning sensation showed the same distribution. The characteristic dermatitis, as well as the other side effects mentioned, occur dose-dependently within the normal therapeutic range of Ro 10-9359 for psoriasis (0.5--1 mg/kg bodyweight daily).", "contents": "[Side effects of oral retinoid Ro 10-9359 on the unaffected skin of psoriatic patients: retinoid dermatitis]. Dermatitis occurring as a side effect in psoriatic patients during oral administration of the retinoid acid derivative Ro 10-9359 is described. This so-called retinoid dermatitis exhibits a characteristic disseminated pattern. Sites of predilection are the face, the exterior surface of the upper and the interior surface of the lower arms, the superior thoracic aperture, the back of the hands and the flanks. The lesions present as follicular papules and/or vesicles. The histological picture is that of acute non-specific dermatitis. This retinoid dermatitis was observed in 9 our of 23 patients (39%) treated with Ro 10-9359. Other side effect such as erythema, desquamation, itching and, rarely, a burning sensation showed the same distribution. The characteristic dermatitis, as well as the other side effects mentioned, occur dose-dependently within the normal therapeutic range of Ro 10-9359 for psoriasis (0.5--1 mg/kg bodyweight daily)."} {"id": "PMID:161416", "title": "The host/parasite relationships of Xenopsylla astia and X. cheopis on Bandicota bengalensis in Rangoon, Burma.", "content": "In Rangoon, Burma, over half the commensal B. bengalensis taken in live traps were found to be infested with Xenopsylla species fleas. X. astia infestations were twice as common as those of the classic plague vector X. cheopis. In terms of absolute numbers X. astia outnumbered X. cheopis by 10 to 1. X. astia was more commonly found as a monospecific infestation, and X. cheopis was more commonly found mixed with X. astia. The flea indicies were high, with a specific index of 2.4 for X. cheopis and 10.2 for X. astia. The flea indicies and flea sex ratios remained stable across the host population and could not be correlated to changes in the head and body length of the host and were not different on male or female hosts. The evidence of this and other surveys is that X. cheopis is not as well adapted for parasitism on free ranging B. bengalensis as is X. astia.", "contents": "The host/parasite relationships of Xenopsylla astia and X. cheopis on Bandicota bengalensis in Rangoon, Burma. In Rangoon, Burma, over half the commensal B. bengalensis taken in live traps were found to be infested with Xenopsylla species fleas. X. astia infestations were twice as common as those of the classic plague vector X. cheopis. In terms of absolute numbers X. astia outnumbered X. cheopis by 10 to 1. X. astia was more commonly found as a monospecific infestation, and X. cheopis was more commonly found mixed with X. astia. The flea indicies were high, with a specific index of 2.4 for X. cheopis and 10.2 for X. astia. The flea indicies and flea sex ratios remained stable across the host population and could not be correlated to changes in the head and body length of the host and were not different on male or female hosts. The evidence of this and other surveys is that X. cheopis is not as well adapted for parasitism on free ranging B. bengalensis as is X. astia."} {"id": "PMID:161417", "title": "Retinoic acid cream (Airol cream) and benzoyl-peroxide in the treatment of acne vulgaris.", "content": "A clinical trial using Airol cream (retinoic acid cream 0.05%), Panoxyl-5 and Panoxyl-10 (benzoyl-peroxide alcoholic gel 5% & 10%) in combination and alone as topical applications for 10 weeks was carried out on 150 ambulatory patients with acne vulgaris. The results based on efficacy, drug tolerance and treatment duration show that the combined use of Panoxyl and Airol is superior to the use of either drug alone and that the combination of Airol cream (0.05%) in the morning and Panoxyl gel (5%) before retiring was the most satisfactory.", "contents": "Retinoic acid cream (Airol cream) and benzoyl-peroxide in the treatment of acne vulgaris. A clinical trial using Airol cream (retinoic acid cream 0.05%), Panoxyl-5 and Panoxyl-10 (benzoyl-peroxide alcoholic gel 5% & 10%) in combination and alone as topical applications for 10 weeks was carried out on 150 ambulatory patients with acne vulgaris. The results based on efficacy, drug tolerance and treatment duration show that the combined use of Panoxyl and Airol is superior to the use of either drug alone and that the combination of Airol cream (0.05%) in the morning and Panoxyl gel (5%) before retiring was the most satisfactory."} {"id": "PMID:161433", "title": "Isolation of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol from ester fractions of nutritionally deprived Neurospora crassa.", "content": "A method of isolating pure fractions of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-38-ol for sterol intermediate studies is described. Starvation cultures of Neurospora crassa readily incorporate exogenous mevalonic acid into the sterol ester fraction. Isolation involves a simple solvent extraction and two chromatograms. Only the ester fraction yielded the required purity. Radioactive 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol is readily produced from DL-[2-14C] mevalonic acid.", "contents": "Isolation of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol from ester fractions of nutritionally deprived Neurospora crassa. A method of isolating pure fractions of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-38-ol for sterol intermediate studies is described. Starvation cultures of Neurospora crassa readily incorporate exogenous mevalonic acid into the sterol ester fraction. Isolation involves a simple solvent extraction and two chromatograms. Only the ester fraction yielded the required purity. Radioactive 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol is readily produced from DL-[2-14C] mevalonic acid."} {"id": "PMID:161434", "title": "Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase.", "content": "The metabolism of 7-(3)H-pregnenolone was studied in vitro using 16 human breast carcinomas. All mammary tumors transformed pregnenolone to progesterone. All estrogen receptor poor tumors and 4 out of 8 estrogen receptor rich tumors converted pregnenolone to 17-hydroxypregnenolone. Five estrogen receptor poor tumors showed the presence of 17,20-lyase as evidenced by formation of dehydroepiandrosterone and androstenedione. In two estrogen receptor poor tumors, conversions of pregnenolone to progesterone, 17-hydroxy pregnenolone, dehydroepiandrosterone, androstenedione and finally to estradiol was documented, providing a hypothetical pathway for steroid metabolism in human breast cancer. The conversion of pregnenolone to 17-hydroxypregnenolone was significantly less in receptor rich tumors and was totally absent in 4 receptor rich tumors with estrogen receptors of over 45 fmol/mg protein.", "contents": "Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase. The metabolism of 7-(3)H-pregnenolone was studied in vitro using 16 human breast carcinomas. All mammary tumors transformed pregnenolone to progesterone. All estrogen receptor poor tumors and 4 out of 8 estrogen receptor rich tumors converted pregnenolone to 17-hydroxypregnenolone. Five estrogen receptor poor tumors showed the presence of 17,20-lyase as evidenced by formation of dehydroepiandrosterone and androstenedione. In two estrogen receptor poor tumors, conversions of pregnenolone to progesterone, 17-hydroxy pregnenolone, dehydroepiandrosterone, androstenedione and finally to estradiol was documented, providing a hypothetical pathway for steroid metabolism in human breast cancer. The conversion of pregnenolone to 17-hydroxypregnenolone was significantly less in receptor rich tumors and was totally absent in 4 receptor rich tumors with estrogen receptors of over 45 fmol/mg protein."} {"id": "PMID:161435", "title": "The in vivo metabolism of 7 beta, 17-dimethyltestosterone-6,7-3H.", "content": "7 beta, 17-Dimethyltestosterone (17 beta-hydroxy-7 beta, 17-dimethyl-4-androsten-3-one) (I) was given to three subjects in oral doses of 400 mg per day for ten days. The initial dose contained the steroid tritiated in the 6 and 7 positions. Plasma levels and urinary excretion patterns were followed in all three subjects. Isolations were done on the urine, plasma, and stools of one patient. From the urine 7 beta, 17-dimethyl- 5 alpha-androstane-3 beta,17 beta-diol (VI) was isolated from the nonhydrolyzed fractions. Unchanged (I), 7 beta,17-dimethyl-5 beta-androstane-3 alpha,17 beta-diol (III) and 7 beta, 17-dimethyl-5 beta-androstane-3 beta,17 beta-diol (IV) were isolated from the nonhydrolyzed and enzyme-hydrolyzed fractions. 7 beta,17-dimethyl-5 alpha-androstane-3 alpha,17 beta-diol (V) was isolated from the enzymatic fractions. From the stools were isolated unchanged (I), (III), (IV), (V), and (VI). Unchanged (I) and its 5 alpha-dihydro derivative (17 beta-hydroxy-7 beta,17-dimethyl-5 alpha-androstan-3-one) (II) were identified in the plasma. The total recovery of radioactivity in the one patient on whom the isolations were done was 57%; 40% from the urine and 17% from the stools.", "contents": "The in vivo metabolism of 7 beta, 17-dimethyltestosterone-6,7-3H. 7 beta, 17-Dimethyltestosterone (17 beta-hydroxy-7 beta, 17-dimethyl-4-androsten-3-one) (I) was given to three subjects in oral doses of 400 mg per day for ten days. The initial dose contained the steroid tritiated in the 6 and 7 positions. Plasma levels and urinary excretion patterns were followed in all three subjects. Isolations were done on the urine, plasma, and stools of one patient. From the urine 7 beta, 17-dimethyl- 5 alpha-androstane-3 beta,17 beta-diol (VI) was isolated from the nonhydrolyzed fractions. Unchanged (I), 7 beta,17-dimethyl-5 beta-androstane-3 alpha,17 beta-diol (III) and 7 beta, 17-dimethyl-5 beta-androstane-3 beta,17 beta-diol (IV) were isolated from the nonhydrolyzed and enzyme-hydrolyzed fractions. 7 beta,17-dimethyl-5 alpha-androstane-3 alpha,17 beta-diol (V) was isolated from the enzymatic fractions. From the stools were isolated unchanged (I), (III), (IV), (V), and (VI). Unchanged (I) and its 5 alpha-dihydro derivative (17 beta-hydroxy-7 beta,17-dimethyl-5 alpha-androstan-3-one) (II) were identified in the plasma. The total recovery of radioactivity in the one patient on whom the isolations were done was 57%; 40% from the urine and 17% from the stools."} {"id": "PMID:161436", "title": "Enzyme analyses of Bulinus africanus group snails (Mollusca: Planorbidae) from Tanzania.", "content": "38 population samples of snails of the Bulinus africanus group, collected from three separate areas of Tanzania, have been examined. Enzymes in crude digestive gland extracts of individual snails have been analysed by isoelectric focusing in polyacrylamide gels. The enzymes studied were: malate dehydrogenase (MDH); phosphoglucomutase (PGM); glucosephosphate isomerase (GPI); acid phosphatase (AcP) and hydroxybutyrate dehydrogenase (HBDH). Samples of B. nasutus were clearly differentiated from other species and enzyme differences were apparent between samples from the lake and coastal areas. Similarly, although clear distinctions could not always be made, samples of B. africanus, B. globosus and B. ugandae were characterized by their enzyme types. Individual variation was detected within populations and the significance of enzyme polymorphisms in relation to identification has been considered. No correlation was found between snail enzyme type and susceptibility to Schistosoma haematobium or S. bovis.", "contents": "Enzyme analyses of Bulinus africanus group snails (Mollusca: Planorbidae) from Tanzania. 38 population samples of snails of the Bulinus africanus group, collected from three separate areas of Tanzania, have been examined. Enzymes in crude digestive gland extracts of individual snails have been analysed by isoelectric focusing in polyacrylamide gels. The enzymes studied were: malate dehydrogenase (MDH); phosphoglucomutase (PGM); glucosephosphate isomerase (GPI); acid phosphatase (AcP) and hydroxybutyrate dehydrogenase (HBDH). Samples of B. nasutus were clearly differentiated from other species and enzyme differences were apparent between samples from the lake and coastal areas. Similarly, although clear distinctions could not always be made, samples of B. africanus, B. globosus and B. ugandae were characterized by their enzyme types. Individual variation was detected within populations and the significance of enzyme polymorphisms in relation to identification has been considered. No correlation was found between snail enzyme type and susceptibility to Schistosoma haematobium or S. bovis."} {"id": "PMID:161441", "title": "[The value of laparoscopy within the framework of standardization of the diagnosis of stomach neoplasms].", "content": "Today the operative treatment of the carcinoma of the stomach is methodically mature. The prognosis is determined from the moment of the extension of the tumour. The establishment of the operability and of the tactical operative approach presumes an exact preoperative determination of the stage of the tumour using all possible diagnostic methods. While X-ray examination of the stomach and gastroscopy seize only the extension of the area of the tumour, the laparoscopy gives the possibility of an evidence of the deep growth of the tumour and metastasizing of the tumour and saves a test laparotomy for inoperable patients. A continuous interdisciplinary cooperation renders possible an immediate admission of the patient to a surgical clinic.", "contents": "[The value of laparoscopy within the framework of standardization of the diagnosis of stomach neoplasms]. Today the operative treatment of the carcinoma of the stomach is methodically mature. The prognosis is determined from the moment of the extension of the tumour. The establishment of the operability and of the tactical operative approach presumes an exact preoperative determination of the stage of the tumour using all possible diagnostic methods. While X-ray examination of the stomach and gastroscopy seize only the extension of the area of the tumour, the laparoscopy gives the possibility of an evidence of the deep growth of the tumour and metastasizing of the tumour and saves a test laparotomy for inoperable patients. A continuous interdisciplinary cooperation renders possible an immediate admission of the patient to a surgical clinic."} {"id": "PMID:161442", "title": "[Sudden cardiac death due to myocardial sarcoidosis].", "content": "The participation of the myocardium in sarcoidosis is a severe complication which in very rare cases may lead to the acute cardiac death. Morphological problems result from all accessory cardiac changes.", "contents": "[Sudden cardiac death due to myocardial sarcoidosis]. The participation of the myocardium in sarcoidosis is a severe complication which in very rare cases may lead to the acute cardiac death. Morphological problems result from all accessory cardiac changes."} {"id": "PMID:161443", "title": "[Excretion of acid mucopolysaccharides in the urine and sweat in hereditary bullous epidermolysis].", "content": "Urine samples of five patients with epidermolysis bullosa hereditaria were examined for the presence of acid glycosaminoglycans (GAG) and compared to 10 healthy subjects. A significant increase (p less than 0.0005) could be detected in patients with epidermolysis (t = 6.66, means: 49.7 mg/day, standard deviation: +/- 18.3). Additionally, acid glycosaminoglycan concentration in sweat of patients and healthy controls was determined but statistical calculations showed no significant difference (p less than 0.15). On grounds of the increased mucopolysaccharide excretion and the previous studies of collagen-glycosaminoglycan interactions, we strongly suggest that acid GAG are involved in the pathogenesis of that disease with the molecular defect of disturbed fibril formation due to the altered skin collagen-glycosaminoglycan equilibrium.", "contents": "[Excretion of acid mucopolysaccharides in the urine and sweat in hereditary bullous epidermolysis]. Urine samples of five patients with epidermolysis bullosa hereditaria were examined for the presence of acid glycosaminoglycans (GAG) and compared to 10 healthy subjects. A significant increase (p less than 0.0005) could be detected in patients with epidermolysis (t = 6.66, means: 49.7 mg/day, standard deviation: +/- 18.3). Additionally, acid glycosaminoglycan concentration in sweat of patients and healthy controls was determined but statistical calculations showed no significant difference (p less than 0.15). On grounds of the increased mucopolysaccharide excretion and the previous studies of collagen-glycosaminoglycan interactions, we strongly suggest that acid GAG are involved in the pathogenesis of that disease with the molecular defect of disturbed fibril formation due to the altered skin collagen-glycosaminoglycan equilibrium."} {"id": "PMID:161444", "title": "Mechanism of paraquat action: inhibition of the herbicidal effect by a copper chelate with superoxide dismutating activity.", "content": "The treatment of flax cotyledons (Linium usitatissimum) with paraquat was shown to decrease the levels of chlorophyll and carotenoid pigments. The fatty acid content of chloroplast fragments isolated from treated tissue was determined and shown to be greatly decreased by paraquat treatment. The superoxide radical was demonstrated to play an important role in the phytotoxic action of paraquat by the use of a copper chelate of D-penicillamine, which has a high superoxide is discussed with reference to the generation of more toxic species, such as singlet oxygen.", "contents": "Mechanism of paraquat action: inhibition of the herbicidal effect by a copper chelate with superoxide dismutating activity. The treatment of flax cotyledons (Linium usitatissimum) with paraquat was shown to decrease the levels of chlorophyll and carotenoid pigments. The fatty acid content of chloroplast fragments isolated from treated tissue was determined and shown to be greatly decreased by paraquat treatment. The superoxide radical was demonstrated to play an important role in the phytotoxic action of paraquat by the use of a copper chelate of D-penicillamine, which has a high superoxide is discussed with reference to the generation of more toxic species, such as singlet oxygen."} {"id": "PMID:161449", "title": "[Experimental assessment of the effectiveness of general and local caries preventives by the use of complex factor analyses (author's transl)].", "content": "Using the method of complex factor analysis, it was possible to characterize the results of experiments conducted with a view to determining the anticariogenic effects upon 104 Wistar rats of fluoridated water, fluoride-containing gel, and remineralizing solutions. The anticariogenic effects were highest for fluoridated drinking water, less satisfactory for fluoride-containing gels, and minimal for remineralizing solutions. Simultaneous application of these anticarious agents was seen to exert an increased inhibitory action upon the progress of dental caries. A typical example is used to show that the use of complex factor analysis yields additional results showing the interaction of the factors being studied and substantially reduces the number of test animals and the time required for experimentation.", "contents": "[Experimental assessment of the effectiveness of general and local caries preventives by the use of complex factor analyses (author's transl)]. Using the method of complex factor analysis, it was possible to characterize the results of experiments conducted with a view to determining the anticariogenic effects upon 104 Wistar rats of fluoridated water, fluoride-containing gel, and remineralizing solutions. The anticariogenic effects were highest for fluoridated drinking water, less satisfactory for fluoride-containing gels, and minimal for remineralizing solutions. Simultaneous application of these anticarious agents was seen to exert an increased inhibitory action upon the progress of dental caries. A typical example is used to show that the use of complex factor analysis yields additional results showing the interaction of the factors being studied and substantially reduces the number of test animals and the time required for experimentation."} {"id": "PMID:161450", "title": "[Testing a method of using fluoride in the treatment of periodontal diseases (author's transl)].", "content": "Factorial planning of the program of testing provided significant evidence that, under the influence of a periodontally pathogenetic diet administered to animals, the enteral supply of fluoride tends to normalize the incorporation of Ca45 and P32 into the mineral fraction and further disturb the incorporation of P32 and lysine-1 C14 into the protein fraction of the bone tissue of the femur and jaw, respectively. Calcium electrophoresis provides for the normalization of the corresponding value of protein metabolism (incorporation of P32 and lysine-1 C14 into the organic fraction) in calcified tissues. Combined use of two therapeutic factors produces most favorable effects upon both the mineral and protein metabolism. This also reduces the negative effect exerted by the use of fluorine alone.", "contents": "[Testing a method of using fluoride in the treatment of periodontal diseases (author's transl)]. Factorial planning of the program of testing provided significant evidence that, under the influence of a periodontally pathogenetic diet administered to animals, the enteral supply of fluoride tends to normalize the incorporation of Ca45 and P32 into the mineral fraction and further disturb the incorporation of P32 and lysine-1 C14 into the protein fraction of the bone tissue of the femur and jaw, respectively. Calcium electrophoresis provides for the normalization of the corresponding value of protein metabolism (incorporation of P32 and lysine-1 C14 into the organic fraction) in calcified tissues. Combined use of two therapeutic factors produces most favorable effects upon both the mineral and protein metabolism. This also reduces the negative effect exerted by the use of fluorine alone."} {"id": "PMID:161451", "title": "[Changes in microhardness of hard dental tissues of rabbits after internal medication of antibiotics (author's transl)].", "content": "Comparative Vickers hardness measurements on hard dental tissues mineralized under normal conditions and under the influence of antibiotic substances showed substance-and dose-dependent variations in quality of superficial enamel and dentine. They were found to correlate with other physicochemical properties (acid solubility) and must be considered as belonging to what is generally referred to as structural anomalies. - Consequently, the administration of antibiotics to babies and young children should be reexamined because of possible late effects.", "contents": "[Changes in microhardness of hard dental tissues of rabbits after internal medication of antibiotics (author's transl)]. Comparative Vickers hardness measurements on hard dental tissues mineralized under normal conditions and under the influence of antibiotic substances showed substance-and dose-dependent variations in quality of superficial enamel and dentine. They were found to correlate with other physicochemical properties (acid solubility) and must be considered as belonging to what is generally referred to as structural anomalies. - Consequently, the administration of antibiotics to babies and young children should be reexamined because of possible late effects."} {"id": "PMID:161452", "title": "[Phantom head used to acquire skill in local anesthesia in the mandibular and maxillary regions (author's transl)].", "content": "This paper describes a phantom head used to acquire skill in local anesthesia in the mandibular and maxillary regions, thus helping students in putting theoretical knowledge into practice. An electric display device enables the student's proficiency level to be determined objectively. Five years' clinical testing of the phantom in the practical training of students shows the advantages of simulatory methods of training. Although this form of instruction cannot of course be regarded as an alternative to practical anesthetizing exercises on patients, yet it has proved a valuable addition to the various possible ways of putting theoretical knowledge into clinical practice.", "contents": "[Phantom head used to acquire skill in local anesthesia in the mandibular and maxillary regions (author's transl)]. This paper describes a phantom head used to acquire skill in local anesthesia in the mandibular and maxillary regions, thus helping students in putting theoretical knowledge into practice. An electric display device enables the student's proficiency level to be determined objectively. Five years' clinical testing of the phantom in the practical training of students shows the advantages of simulatory methods of training. Although this form of instruction cannot of course be regarded as an alternative to practical anesthetizing exercises on patients, yet it has proved a valuable addition to the various possible ways of putting theoretical knowledge into clinical practice."} {"id": "PMID:161453", "title": "[On the significance of severely keratinizing squamous cell carcinomata in the oral cavity (author's transl)]].", "content": "Severely keratinizing squamous cell carcinomata are very infrequently observed oral cavity tumors with a relatively nonmalignant character. Problems of clinical diagnosis and the significance of such carcinomata are discussed with reference to the case history of a 38-year-old male patient.", "contents": "[On the significance of severely keratinizing squamous cell carcinomata in the oral cavity (author's transl)]]. Severely keratinizing squamous cell carcinomata are very infrequently observed oral cavity tumors with a relatively nonmalignant character. Problems of clinical diagnosis and the significance of such carcinomata are discussed with reference to the case history of a 38-year-old male patient."} {"id": "PMID:161454", "title": "[Comparative studies of the influence of osteoplasty upon maxillary growth (author's transl)].", "content": "Model series of patients with cheiloschisis, gnathoschisis, and palatoschisis, who at the age of 4 to 6 had been undergoing surgical operations with simultaneous osteoplasty, were examined, at the age of 9 to 16, for the maxillary growth in length and width. Serving as a reference group were models of patients of a morphologically similar group where the operation for cleft palate had been performed by the same technique, but without additional osteoplasty. It was not possible to obtain statistical evidence for a negative influence of osteoplasty upon maxillary growth.", "contents": "[Comparative studies of the influence of osteoplasty upon maxillary growth (author's transl)]. Model series of patients with cheiloschisis, gnathoschisis, and palatoschisis, who at the age of 4 to 6 had been undergoing surgical operations with simultaneous osteoplasty, were examined, at the age of 9 to 16, for the maxillary growth in length and width. Serving as a reference group were models of patients of a morphologically similar group where the operation for cleft palate had been performed by the same technique, but without additional osteoplasty. It was not possible to obtain statistical evidence for a negative influence of osteoplasty upon maxillary growth."} {"id": "PMID:161455", "title": "[Clinical-morphological report for adenomatoid odontogenic tumor (author's transl)].", "content": "The adenomatoid odontogenic tumor is a benign lesion mostly detected as a random finding. Often the lesion is thought to be an odontogenic cyst owing to its clinical and radiographical appearance. Only histological investigation enables correct diagnosis. The case of adenomatoid odontogenic tumor of a 20-year-old woman is reported. The tumor was taken for a globulo-maxillary cyst. - The typical histological picture prevents confusion with other odontogenic tumors. Simple exstirpation is sufficient.", "contents": "[Clinical-morphological report for adenomatoid odontogenic tumor (author's transl)]. The adenomatoid odontogenic tumor is a benign lesion mostly detected as a random finding. Often the lesion is thought to be an odontogenic cyst owing to its clinical and radiographical appearance. Only histological investigation enables correct diagnosis. The case of adenomatoid odontogenic tumor of a 20-year-old woman is reported. The tumor was taken for a globulo-maxillary cyst. - The typical histological picture prevents confusion with other odontogenic tumors. Simple exstirpation is sufficient."} {"id": "PMID:161458", "title": "Circulatory effects of somatostatin in anesthetized man.", "content": "The effect of intravenous somatostatin (1 microgram.kg-1 over 1 min) on arterial pressure and on the blood flow to various splanchnic organs, skeletal muscle and brain tissue was studied by means of electromagnetic blood flow measurements in patients undergoing abdominal surgery or reconstructive surgery of the internal carotid artery. Somatostatin infusion reduced the blood flow in the common hepatic artery by 56%, in the splenic artery by 26%, in the ileocolic artery by 34% and in the left colic artery by 36%. External iliac artery blood flow was increased by 43% while internal carotid artery blood flow was unchanged. Mean arterial pressure was increased by 20%. It is suggested that these circulatory effects of somatostatin are due to a direct effect of somatostatin on vascular smooth muscle.", "contents": "Circulatory effects of somatostatin in anesthetized man. The effect of intravenous somatostatin (1 microgram.kg-1 over 1 min) on arterial pressure and on the blood flow to various splanchnic organs, skeletal muscle and brain tissue was studied by means of electromagnetic blood flow measurements in patients undergoing abdominal surgery or reconstructive surgery of the internal carotid artery. Somatostatin infusion reduced the blood flow in the common hepatic artery by 56%, in the splenic artery by 26%, in the ileocolic artery by 34% and in the left colic artery by 36%. External iliac artery blood flow was increased by 43% while internal carotid artery blood flow was unchanged. Mean arterial pressure was increased by 20%. It is suggested that these circulatory effects of somatostatin are due to a direct effect of somatostatin on vascular smooth muscle."} {"id": "PMID:161459", "title": "Acute perihepatitis.", "content": "Fourteen young females with acute pains in the right hypochondrium were admitted to the Surgical Department. The history and clinical findings were typical of acute perihepatitis (Fitz-Hugh-Curtis syndrome), and the diagnosis was confirmed by laparoscopy. The gynecological symptoms and signs were negligible, and Neisseria gonorrhoeae were cultured from the endocervix in two of the patients. Pathogenes in the suprahepatic space were not demonstrated. Eight patients used intrauterine contraceptive device (IUD) of the Copper-T-type. Acute perihepatitis is an important differential diagnosis in young females presenting with acute pains in the right hypochondrium.", "contents": "Acute perihepatitis. Fourteen young females with acute pains in the right hypochondrium were admitted to the Surgical Department. The history and clinical findings were typical of acute perihepatitis (Fitz-Hugh-Curtis syndrome), and the diagnosis was confirmed by laparoscopy. The gynecological symptoms and signs were negligible, and Neisseria gonorrhoeae were cultured from the endocervix in two of the patients. Pathogenes in the suprahepatic space were not demonstrated. Eight patients used intrauterine contraceptive device (IUD) of the Copper-T-type. Acute perihepatitis is an important differential diagnosis in young females presenting with acute pains in the right hypochondrium."} {"id": "PMID:161460", "title": "[Characteristics of the erythrocyte movement in the vicinity of the flow chamber wall].", "content": "In perfusion experiments it was demonstrated that in close vicinity to the lower wall of a microscopic flow chamber a fraction of red blood cells do not exhibit the typical rotational motion, but flow in a steady position with the flat surface to the wall. The velocity of these cells is significantly smaller than that of the fluid in the same region of the channel. It is suggested that the phenomenon is caused by the action of adhesion-type forces operating between the flowing cells and the channel wall.", "contents": "[Characteristics of the erythrocyte movement in the vicinity of the flow chamber wall]. In perfusion experiments it was demonstrated that in close vicinity to the lower wall of a microscopic flow chamber a fraction of red blood cells do not exhibit the typical rotational motion, but flow in a steady position with the flat surface to the wall. The velocity of these cells is significantly smaller than that of the fluid in the same region of the channel. It is suggested that the phenomenon is caused by the action of adhesion-type forces operating between the flowing cells and the channel wall."} {"id": "PMID:161461", "title": "[Pulmonary function tests with the bronchodilator Terbutaline].", "content": "The acute bronchodilator effect of the beta 2-adrenoceptor agonist terbutaline was tested single-blind cross-over in out-patients with chronic obstructive airways disease (intrinsic asthma). In 7 series comparisons were made with other marketed bronchodilators. Airways resistance was measured by whole body plethysmography. In another 3 series the effect on heart rate of terbutaline and other adrenocepter agonists was tested in healthy volunteers. Terbutaline and the adrenoceptor agonists clenbuterol, epinephrine, fenoterol, hexoprenaline, isoprenaline, metaproterenol, reproterol and salbutamol, the vagolytics atropine, ipratropium bromide and AA 22-263, the xanthinederivative theophylline ethylenediamine and one combined substance drug were used.", "contents": "[Pulmonary function tests with the bronchodilator Terbutaline]. The acute bronchodilator effect of the beta 2-adrenoceptor agonist terbutaline was tested single-blind cross-over in out-patients with chronic obstructive airways disease (intrinsic asthma). In 7 series comparisons were made with other marketed bronchodilators. Airways resistance was measured by whole body plethysmography. In another 3 series the effect on heart rate of terbutaline and other adrenocepter agonists was tested in healthy volunteers. Terbutaline and the adrenoceptor agonists clenbuterol, epinephrine, fenoterol, hexoprenaline, isoprenaline, metaproterenol, reproterol and salbutamol, the vagolytics atropine, ipratropium bromide and AA 22-263, the xanthinederivative theophylline ethylenediamine and one combined substance drug were used."} {"id": "PMID:161466", "title": "Hemihypertrophy with unilateral folliculitis and acne.", "content": "A case of congenital hemihypertrophy, right-sided folliculitis and acne in a 16-year-old boy is described. Except for hemihypertrophy and skin changes on the right side, no other abnormalities were found. A similar combination could not be found in the literature.", "contents": "Hemihypertrophy with unilateral folliculitis and acne. A case of congenital hemihypertrophy, right-sided folliculitis and acne in a 16-year-old boy is described. Except for hemihypertrophy and skin changes on the right side, no other abnormalities were found. A similar combination could not be found in the literature."} {"id": "PMID:161467", "title": "Differences in urinary trichloroethylene metabolites of animals.", "content": "Differences in urinary excretion of trichloroethylene were studied in rabbits, rats and mice. Trichloretylene (1 m mole/kg) was injected intra-peritoneally, then urinary trichloroacetic acid and trichloroethanol glucuronide were measured. The results were: 1. The ratio of total excretion of trichloroethylene metabolites to the administered trichloroethylene decreased in the order of mice, rats and rabbits. 2. The ratio of total trichloroethanol to trichloroacetic acid in urine decreased in the order of rabbits (69.2), mice (12.8) and rats (2.3). The high ratio in rabbits was due to the extremely small amount of trichloroacetic acid in the urine. 3. Differences in these two urinary metabolites in the three kinds of animals and in human subjects were discussed.", "contents": "Differences in urinary trichloroethylene metabolites of animals. Differences in urinary excretion of trichloroethylene were studied in rabbits, rats and mice. Trichloretylene (1 m mole/kg) was injected intra-peritoneally, then urinary trichloroacetic acid and trichloroethanol glucuronide were measured. The results were: 1. The ratio of total excretion of trichloroethylene metabolites to the administered trichloroethylene decreased in the order of mice, rats and rabbits. 2. The ratio of total trichloroethanol to trichloroacetic acid in urine decreased in the order of rabbits (69.2), mice (12.8) and rats (2.3). The high ratio in rabbits was due to the extremely small amount of trichloroacetic acid in the urine. 3. Differences in these two urinary metabolites in the three kinds of animals and in human subjects were discussed."} {"id": "PMID:161468", "title": "Scanning electron microscopy of interaction of peripheral blood lymphocytes from colonic cancer patients with human colonic cancer-derived cells; P-4788.", "content": "Peripheral blood lymphocytes and the various lymphocyte fractions from patients with cancer of the colon were cultivated with target cells (P-4788) derived from the colon cancer. Changes in the surface ultrastructure during tumor cell destruction were studied by scanning electron microscopy (SEM). P-4788 cells adhering to the coverslip showed various surface activity. The surfaces of some cells were relatively flat; others were smooth or had fine granules. Still other cells were villous, round or had marked blebs. When host lymphocytes were added to the target cells, adhesion of the two cell groups began by many fine projections. After incubation for 6 h, some lymphocytes had adhered to the target cells. Many lymphocytes had adhered to the target tumor cells by 24--48 h incubation. Ultimately the tumor cells became swollen and disrupted. Most lymphocytes adherent to the target cells had few microvilli. Lymphocytes after elimination of phagocytes by carbonyl iron treatment also adhered readily. Some target cells showed adhesion with lymphocytes passed through nylon-wool columns, although the number of lymphocytes adhering was fewer than in the case of lymphocytes not passed through nylon-wool columns. T cells were collected from lymphocytes that form rosettes with SRBC by isolation with NH4Cl. They had markedly elongated microvilli which in places were sparsely scattered and tended to be localized on the side, a finding which suggests loss of cell activity by the time of SEM. Only a few T cells adhered to target cells and they seemed to be T cells without activity. It was thought that there are cytotoxic cells among T cells and that the co-existence of T cells, non-T cells and monocytes caused target cell destruction.", "contents": "Scanning electron microscopy of interaction of peripheral blood lymphocytes from colonic cancer patients with human colonic cancer-derived cells; P-4788. Peripheral blood lymphocytes and the various lymphocyte fractions from patients with cancer of the colon were cultivated with target cells (P-4788) derived from the colon cancer. Changes in the surface ultrastructure during tumor cell destruction were studied by scanning electron microscopy (SEM). P-4788 cells adhering to the coverslip showed various surface activity. The surfaces of some cells were relatively flat; others were smooth or had fine granules. Still other cells were villous, round or had marked blebs. When host lymphocytes were added to the target cells, adhesion of the two cell groups began by many fine projections. After incubation for 6 h, some lymphocytes had adhered to the target cells. Many lymphocytes had adhered to the target tumor cells by 24--48 h incubation. Ultimately the tumor cells became swollen and disrupted. Most lymphocytes adherent to the target cells had few microvilli. Lymphocytes after elimination of phagocytes by carbonyl iron treatment also adhered readily. Some target cells showed adhesion with lymphocytes passed through nylon-wool columns, although the number of lymphocytes adhering was fewer than in the case of lymphocytes not passed through nylon-wool columns. T cells were collected from lymphocytes that form rosettes with SRBC by isolation with NH4Cl. They had markedly elongated microvilli which in places were sparsely scattered and tended to be localized on the side, a finding which suggests loss of cell activity by the time of SEM. Only a few T cells adhered to target cells and they seemed to be T cells without activity. It was thought that there are cytotoxic cells among T cells and that the co-existence of T cells, non-T cells and monocytes caused target cell destruction."} {"id": "PMID:161469", "title": "An animal model of fulminant hepatic failure in the rat.", "content": "A reproducible animal model of fulminant hepatic failure was developed by intraperitoneal administration of D-galactosamine hydrochloride to Sprague-Dawley rats. Biochemical and morphological hepatic injury and brain edema resembled human fulminant hepatic failure. This model would facilitate further studies of the pathogenesis of brain dysfunction and evaluation of treatment in fulminant hepatic failure.", "contents": "An animal model of fulminant hepatic failure in the rat. A reproducible animal model of fulminant hepatic failure was developed by intraperitoneal administration of D-galactosamine hydrochloride to Sprague-Dawley rats. Biochemical and morphological hepatic injury and brain edema resembled human fulminant hepatic failure. This model would facilitate further studies of the pathogenesis of brain dysfunction and evaluation of treatment in fulminant hepatic failure."} {"id": "PMID:161470", "title": "The tumor-forming type of multiple myeloma. II. Clinical profile and therapeutic effect.", "content": "In the six cases of tumor-forming type as described in the part I of this series, the estimated ages at disease onset ranged from 55 to 82 years old. Tumor-forming sites consisted of three cases each in skull and ribs, and one each in pelvis and palate. Bone x-rays revealed usually larger punched-out lesions adjacent to smaller punched-out lesions with tumor formation corresponding to the larger lesion. Plasma cells averaged 5.8% in myelogram, and monoclonal immunoglobulin consisted all of IgG. Clinical stages were in IA in four patients vs. IIA in two, and single or combined chemotherapy worked well on all the patients. A comparative study on decrease of monoclonal immunoglobulin value against chemotherapy between tumor-forming and non-tumor-forming types was made. The uniqueness of the tumor-forming type was emphasized to arouse attention to appropriate therapeutic measures for these patients.", "contents": "The tumor-forming type of multiple myeloma. II. Clinical profile and therapeutic effect. In the six cases of tumor-forming type as described in the part I of this series, the estimated ages at disease onset ranged from 55 to 82 years old. Tumor-forming sites consisted of three cases each in skull and ribs, and one each in pelvis and palate. Bone x-rays revealed usually larger punched-out lesions adjacent to smaller punched-out lesions with tumor formation corresponding to the larger lesion. Plasma cells averaged 5.8% in myelogram, and monoclonal immunoglobulin consisted all of IgG. Clinical stages were in IA in four patients vs. IIA in two, and single or combined chemotherapy worked well on all the patients. A comparative study on decrease of monoclonal immunoglobulin value against chemotherapy between tumor-forming and non-tumor-forming types was made. The uniqueness of the tumor-forming type was emphasized to arouse attention to appropriate therapeutic measures for these patients."} {"id": "PMID:161471", "title": "Malacoplakia of probable retroperitoneal origin.", "content": "A case of extravesical malacoplakia, the first case in Japan, is described in detail. The patient was a 61-year-old woman with a right flank mass. Radiologically, the mass was thought to be of the renal origin. Surgically, however, the tumor was found attached not only to the cortical surface but extended to the retroperitoneum and psoas muscle. Pathological examination confirmed the lesion to be malacoplakia characterized by the presence of von Hansemann cells and Michaelis-Gutmann bodies.", "contents": "Malacoplakia of probable retroperitoneal origin. A case of extravesical malacoplakia, the first case in Japan, is described in detail. The patient was a 61-year-old woman with a right flank mass. Radiologically, the mass was thought to be of the renal origin. Surgically, however, the tumor was found attached not only to the cortical surface but extended to the retroperitoneum and psoas muscle. Pathological examination confirmed the lesion to be malacoplakia characterized by the presence of von Hansemann cells and Michaelis-Gutmann bodies."} {"id": "PMID:161472", "title": "Pseudomyxoma peritonei of ovarian origin--an autopsy case.", "content": "The autopsy case of an 80-year-old female with pseudomyxoma peritonei arising in the left ovary is reported. The patient was admitted with complaints of anorexia, sense of fullness and abdominal distension of two months' duration, and died of intestinal obstruction four months later. The autopsy revealed extensive tumor dissemination over the entire peritoneal cavity without any visceral invasion or distant metastasis. A part of the sigmoid colon showed marked stenosis and perforation with abscess formation. Histologically, the tumor was composed of various sized multiple cysts which were completely or incompletely lined by a layer of mucin-producing columnar epithelial cells with moderate nuclear hyperchromatism, and of a papillary pattern in some parts, indicating low grade malignancy.", "contents": "Pseudomyxoma peritonei of ovarian origin--an autopsy case. The autopsy case of an 80-year-old female with pseudomyxoma peritonei arising in the left ovary is reported. The patient was admitted with complaints of anorexia, sense of fullness and abdominal distension of two months' duration, and died of intestinal obstruction four months later. The autopsy revealed extensive tumor dissemination over the entire peritoneal cavity without any visceral invasion or distant metastasis. A part of the sigmoid colon showed marked stenosis and perforation with abscess formation. Histologically, the tumor was composed of various sized multiple cysts which were completely or incompletely lined by a layer of mucin-producing columnar epithelial cells with moderate nuclear hyperchromatism, and of a papillary pattern in some parts, indicating low grade malignancy."} {"id": "PMID:161473", "title": "Quantitative determination of urinary trichloroacetic acid as an index of trichloroethylene exposure by high performance liquid chromatography.", "content": "A high performance lipuid chromatographic method for the determination of urinary trichloroacetic acid, a metabolite of trichloroethylene, is described. A stainless steel column packed with Hitachi gel 2618 (H form) was used and the mobile phase was one per cent aqueous phosphoric acid. Urine can be analyzed directly without any solvent extraction or pretreatment. The minimal detection limit was 0.5 micrograms per analysis. The present method is simple and specific, and can be performed within 10 min.", "contents": "Quantitative determination of urinary trichloroacetic acid as an index of trichloroethylene exposure by high performance liquid chromatography. A high performance lipuid chromatographic method for the determination of urinary trichloroacetic acid, a metabolite of trichloroethylene, is described. A stainless steel column packed with Hitachi gel 2618 (H form) was used and the mobile phase was one per cent aqueous phosphoric acid. Urine can be analyzed directly without any solvent extraction or pretreatment. The minimal detection limit was 0.5 micrograms per analysis. The present method is simple and specific, and can be performed within 10 min."} {"id": "PMID:161477", "title": "Discriminatory aspects of pre-employment screening: low-back X-ray examinations in the railroad industry.", "content": "In screening the majority of job applicants, most of this nation's railroads administer a low-back X-ray examination in an attempt to ascertain the likelihood that the applicant will sustain future work-related low-back pain or injury. Many applicants are rejected for employment on the basis of the X-ray findings. The railroads apparently perceive this screening program as a cost-effective means (1) of decreasing the incidence of compensation claims for work-related injuries, brought against the railroads under the Federal Employers' Liability Act (FELA), (2) of reducing the number of lost workdays resulting from low-back pain or injury, and (3) of protecting particularly susceptible workers from job-related hazards. The authors of this Article submit that low-back X-ray examinations are poor predictors of future low-back pain or injury. They assert that the railroads' use of such examinations misclassifies a substantial number of job applicants as being at increased risk for such pain or injury, and, in consequence, unfairly denies them employment. Furthermore, the authors claim, the screening program has other negative consequences. For example, applicants rejected for railroad employment on the basis of X-ray findings may as a result have difficulty finding jobs in other industries. In addition, they state, there is a potential radiation hazard to examinees. Moreover, both the railroads and those applicants accepted for employment may inappropriately be reassured by normal findings. On balance, the authors conclude, the screening program has a negative social value. The authors suggest that the program, in effect, erraneously labels many applicants as handicapped, and then denies them employment. Such persons might have legal recourse under federal and state statutes prohibiting employment discrimination against the handicapped.", "contents": "Discriminatory aspects of pre-employment screening: low-back X-ray examinations in the railroad industry. In screening the majority of job applicants, most of this nation's railroads administer a low-back X-ray examination in an attempt to ascertain the likelihood that the applicant will sustain future work-related low-back pain or injury. Many applicants are rejected for employment on the basis of the X-ray findings. The railroads apparently perceive this screening program as a cost-effective means (1) of decreasing the incidence of compensation claims for work-related injuries, brought against the railroads under the Federal Employers' Liability Act (FELA), (2) of reducing the number of lost workdays resulting from low-back pain or injury, and (3) of protecting particularly susceptible workers from job-related hazards. The authors of this Article submit that low-back X-ray examinations are poor predictors of future low-back pain or injury. They assert that the railroads' use of such examinations misclassifies a substantial number of job applicants as being at increased risk for such pain or injury, and, in consequence, unfairly denies them employment. Furthermore, the authors claim, the screening program has other negative consequences. For example, applicants rejected for railroad employment on the basis of X-ray findings may as a result have difficulty finding jobs in other industries. In addition, they state, there is a potential radiation hazard to examinees. Moreover, both the railroads and those applicants accepted for employment may inappropriately be reassured by normal findings. On balance, the authors conclude, the screening program has a negative social value. The authors suggest that the program, in effect, erraneously labels many applicants as handicapped, and then denies them employment. Such persons might have legal recourse under federal and state statutes prohibiting employment discrimination against the handicapped."} {"id": "PMID:161479", "title": "[Device for measurements of blood flow in the great retinal vessels of man (author's transl)].", "content": "A combined measuring unit for the Retinophot is described which can be used to determine the blood flow through the great retinal vessels. This method is possible by combination of the two-point photometry with length measurements by means of rocking-plate micrometry. The first measuring results are presented.", "contents": "[Device for measurements of blood flow in the great retinal vessels of man (author's transl)]. A combined measuring unit for the Retinophot is described which can be used to determine the blood flow through the great retinal vessels. This method is possible by combination of the two-point photometry with length measurements by means of rocking-plate micrometry. The first measuring results are presented."} {"id": "PMID:161478", "title": "Echocardiographic evaluation of the effect of hemodialysis on cardiac size and function in patients with end-stage renal disease.", "content": "Twelve stable patients with end-stage renal failure maintained on hemodialysis were studied by echocardiography before and after dialysis. The left ventricular (LV) end-diastolic wall thickness, interventricular septal thickness and LV mass were increaed suggesting concentric LV hypertrophy. The LV end-diastolic and end-systolic volumes, and cardiac output were increased before dialysis. Aortic root dimensions, aortic valve opening, left atrium, LV wall and septal excursions and per cent LV internal diameter shortening were normal before dialysis. Some pericardial effusion was found in 50% of the patients without any symptoms or signs. With dialysis the systolic and diastolic volumes and dimensions of the left ventricle and atrium decreased significantly as did the stroke volume. These changes were associated with a significant reduction of body weight, and thereby blood volume, induced by dialysis. The cardiac output remained unchanged despite significant reduction in the stroke volume due to an increase in heart rate.", "contents": "Echocardiographic evaluation of the effect of hemodialysis on cardiac size and function in patients with end-stage renal disease. Twelve stable patients with end-stage renal failure maintained on hemodialysis were studied by echocardiography before and after dialysis. The left ventricular (LV) end-diastolic wall thickness, interventricular septal thickness and LV mass were increaed suggesting concentric LV hypertrophy. The LV end-diastolic and end-systolic volumes, and cardiac output were increased before dialysis. Aortic root dimensions, aortic valve opening, left atrium, LV wall and septal excursions and per cent LV internal diameter shortening were normal before dialysis. Some pericardial effusion was found in 50% of the patients without any symptoms or signs. With dialysis the systolic and diastolic volumes and dimensions of the left ventricle and atrium decreased significantly as did the stroke volume. These changes were associated with a significant reduction of body weight, and thereby blood volume, induced by dialysis. The cardiac output remained unchanged despite significant reduction in the stroke volume due to an increase in heart rate."} {"id": "PMID:161490", "title": "The effects of suturing technique and vessel size on patency after microarterial repair.", "content": "According to most of the literature, sutures for microarterial repair must include the intima to prevent an \"intimal flap\" and occlusion of the anastomosis. Some authors have said that vessel diameter affects patency rate. This study was designed to evaluate these two statements. The femoral arteries (about 1.0 mm in diameter), the epigastric arteries (about 0.5 mm), and the central ear arteries (about 0.5 mm) of rabbits were studied. Alternate arteries were repaired using conventional suturing techniques or sutures which included the adventitia and media but excluded the intima. The patency rate in the 1 mm or 0.5 mm vessels was not affected by inclusion or exclusion of the intima from the microarterial repair. The patency rate for conventionally repaired arteries 1 mm in diameter was significantly higher than that for 0.5 mm arteries.", "contents": "The effects of suturing technique and vessel size on patency after microarterial repair. According to most of the literature, sutures for microarterial repair must include the intima to prevent an \"intimal flap\" and occlusion of the anastomosis. Some authors have said that vessel diameter affects patency rate. This study was designed to evaluate these two statements. The femoral arteries (about 1.0 mm in diameter), the epigastric arteries (about 0.5 mm), and the central ear arteries (about 0.5 mm) of rabbits were studied. Alternate arteries were repaired using conventional suturing techniques or sutures which included the adventitia and media but excluded the intima. The patency rate in the 1 mm or 0.5 mm vessels was not affected by inclusion or exclusion of the intima from the microarterial repair. The patency rate for conventionally repaired arteries 1 mm in diameter was significantly higher than that for 0.5 mm arteries."} {"id": "PMID:161491", "title": "Dictyocaulus viviparus in calves: quantitation of antibody activities in sera and respiratory secretions by immuno-enzymatic analysis.", "content": "An enzyme-linked immunosorbent assay (Elisa) which is in detail described here has been adapted to trace antibody production in different fluids from infected calves. Seven calves were infected both with Dictyocaulus viviparus, and with several intestinal nematodes. Antibodies against an antigen prepared from Dictyocaulus viviparus adult worms were first detected during the 5th week post-infection, both in serum and nasal secretions, and were also observed in bronchial washings of the same calves slaughtered 53 days post-infection. IgA antibodies were never evident in the serum but were found in limited quantities in nasal secretions. In bronchial washings at slaughtering, a significant part of antibody activity is accounted for by the local IgA production.", "contents": "Dictyocaulus viviparus in calves: quantitation of antibody activities in sera and respiratory secretions by immuno-enzymatic analysis. An enzyme-linked immunosorbent assay (Elisa) which is in detail described here has been adapted to trace antibody production in different fluids from infected calves. Seven calves were infected both with Dictyocaulus viviparus, and with several intestinal nematodes. Antibodies against an antigen prepared from Dictyocaulus viviparus adult worms were first detected during the 5th week post-infection, both in serum and nasal secretions, and were also observed in bronchial washings of the same calves slaughtered 53 days post-infection. IgA antibodies were never evident in the serum but were found in limited quantities in nasal secretions. In bronchial washings at slaughtering, a significant part of antibody activity is accounted for by the local IgA production."} {"id": "PMID:161492", "title": "Incidence of zearalenol (Fusarium mycotoxin) in animal feed.", "content": "Zearalenol, the reduction product of zearalenone produced by Fusarium roseum growing in cereals, was found for the first time naturally occurring in oats and corn. This metabolite is three to four times more active estrogenically than zearalenone.", "contents": "Incidence of zearalenol (Fusarium mycotoxin) in animal feed. Zearalenol, the reduction product of zearalenone produced by Fusarium roseum growing in cereals, was found for the first time naturally occurring in oats and corn. This metabolite is three to four times more active estrogenically than zearalenone."} {"id": "PMID:161493", "title": "[On the plurifactorial determinism of the organophosphorous-induced teratogenesis on bird embryos; trials of protection by various compounds: oximes, hydroxamic acids and nicotinamide analogs (author's transl)].", "content": "Simple methods were applied to study the teratogenesis in Quail embryos induced by two important organophosphorous compounds: parathion and dicrotophos. Parathion led only to vertebral malformations, as other natural and synthetic cholinomimetics: nicotine, carbamylcholine, decamethonium, neostigmine... Dicrotophos induced not only vertebral malformations (specific to neuromuscular junction poisons) but also beak, legs and feather abnormalities (peripheric malformations which are also produced by insuline and sulfanilamide). Oximes and hydroxamic acids, some of these being analogs of nicotinamide, were tested as antiteratogens. The 3-(CO-NH2), or -(CO-NHOH), substituted pyridinic compounds (nicotinamide, nicotinohydroxamic acid) prevent perfectly dicrotophos-induced beak and legs malformations, in tertiary amine form, but very little in quaternary amine form (methyliodide). The 4-substituted pyridinic compound (isonicotinohydroxamic acid) and aliphatic oxo-oximes were quite ineffecient against these malformations. The vertebral malformations, as a rule, were not lessened by the compounds tested, except for isonicotinoyl-formaldoxime methyl iodide and in some degree for nicotinohydroxamic acid. From these observations, it results that teratogenesis induced by compounds as dicrotophos is rule by a plurificatorial determinism. The beak and legs malformations are prevented by analogs of nicotinamide. In the contrary, the vertebral malformations induced by parathion or dicrotophos are nicotinamide unsensitive and are only prevented by powerful cholinesterase reactivators as pralidoxime or TMB4 (MEINIEL, 1976 b) but are reduced little or not at all by less potent cholinesterase reactivators (HEATH).", "contents": "[On the plurifactorial determinism of the organophosphorous-induced teratogenesis on bird embryos; trials of protection by various compounds: oximes, hydroxamic acids and nicotinamide analogs (author's transl)]. Simple methods were applied to study the teratogenesis in Quail embryos induced by two important organophosphorous compounds: parathion and dicrotophos. Parathion led only to vertebral malformations, as other natural and synthetic cholinomimetics: nicotine, carbamylcholine, decamethonium, neostigmine... Dicrotophos induced not only vertebral malformations (specific to neuromuscular junction poisons) but also beak, legs and feather abnormalities (peripheric malformations which are also produced by insuline and sulfanilamide). Oximes and hydroxamic acids, some of these being analogs of nicotinamide, were tested as antiteratogens. The 3-(CO-NH2), or -(CO-NHOH), substituted pyridinic compounds (nicotinamide, nicotinohydroxamic acid) prevent perfectly dicrotophos-induced beak and legs malformations, in tertiary amine form, but very little in quaternary amine form (methyliodide). The 4-substituted pyridinic compound (isonicotinohydroxamic acid) and aliphatic oxo-oximes were quite ineffecient against these malformations. The vertebral malformations, as a rule, were not lessened by the compounds tested, except for isonicotinoyl-formaldoxime methyl iodide and in some degree for nicotinohydroxamic acid. From these observations, it results that teratogenesis induced by compounds as dicrotophos is rule by a plurificatorial determinism. The beak and legs malformations are prevented by analogs of nicotinamide. In the contrary, the vertebral malformations induced by parathion or dicrotophos are nicotinamide unsensitive and are only prevented by powerful cholinesterase reactivators as pralidoxime or TMB4 (MEINIEL, 1976 b) but are reduced little or not at all by less potent cholinesterase reactivators (HEATH)."} {"id": "PMID:161494", "title": "Surface fixation method applied for the detection of antigen-antibody reactions in mixtures of sera of mothers and children with Down's syndrome.", "content": "An attempt has been made to use the rapid surface fixation method for the investigation of immunological reactions in mixtures of sera from mothers and their mongoloid children. This preliminary report has been encouraging since all positive reactions were properly controlled with the serum of patients suffering from various clinical conditions but free of Down's syndrome. A water soluble substance was isolated from the urine of patients which produced positive reactions like those performed with the serum of mongoloid children.", "contents": "Surface fixation method applied for the detection of antigen-antibody reactions in mixtures of sera of mothers and children with Down's syndrome. An attempt has been made to use the rapid surface fixation method for the investigation of immunological reactions in mixtures of sera from mothers and their mongoloid children. This preliminary report has been encouraging since all positive reactions were properly controlled with the serum of patients suffering from various clinical conditions but free of Down's syndrome. A water soluble substance was isolated from the urine of patients which produced positive reactions like those performed with the serum of mongoloid children."} {"id": "PMID:161495", "title": "[Papillon-Lef\u00e8vre syndrome and recurrent infections].", "content": "Seven cases of Papillon-Lefevre syndrome are described, 4 children and their mother with two other relatives on the mother's side. An immune defect was suspected because six of the seven had a history of severe pyogenic infections, but the results of the tests were not the same in the three individuals tested. In one patient no immune defect was detected but in the other two the response of lymphocytes to candida and to streptokinase and streptodornase was reduced.", "contents": "[Papillon-Lef\u00e8vre syndrome and recurrent infections]. Seven cases of Papillon-Lefevre syndrome are described, 4 children and their mother with two other relatives on the mother's side. An immune defect was suspected because six of the seven had a history of severe pyogenic infections, but the results of the tests were not the same in the three individuals tested. In one patient no immune defect was detected but in the other two the response of lymphocytes to candida and to streptokinase and streptodornase was reduced."} {"id": "PMID:161505", "title": "Linkage, chromosomal association, and expression of Adh-1 and Pgm-2 in tomato.", "content": "The linkage relationship and chromosomal association of two genes in tomato coding for the respiratory enzymes alcohol dehydrogenase and phosphoglucomutase are reported. Also included is a description of where in the life cycle of the plant these genes are expressed. The finding that in pollen and germinating seeds most if not all of the detected activity of these two enzymes apparently arises from these genes suggests that the two isozymes might function in the same respiratory pathway.", "contents": "Linkage, chromosomal association, and expression of Adh-1 and Pgm-2 in tomato. The linkage relationship and chromosomal association of two genes in tomato coding for the respiratory enzymes alcohol dehydrogenase and phosphoglucomutase are reported. Also included is a description of where in the life cycle of the plant these genes are expressed. The finding that in pollen and germinating seeds most if not all of the detected activity of these two enzymes apparently arises from these genes suggests that the two isozymes might function in the same respiratory pathway."} {"id": "PMID:161506", "title": "Genetic and cytogenetic studies of four glycolytic enzymes in Drosophila melanogaster: aldolase, triosephosphate isomerase, 3-phosphoglycerate kinase, and phosphoglucomutase.", "content": "Four glycolytic enzymes in Drosophila melanogaster have been genetically and/or cytogenetically mapped. The structural gene for aldolase (Ald) has been genetically mapped to 3-91.5 and cytogenetically localized to 97A-B. Tpi, the structural gene for triosephosphate isomerase, has been genetically mapped to 3-101.3 and cytogenetically localized to 99B-E. Utilizing closer-flanking markers than the previous mapping, Pgk, the structural gene for 3-phosphoglycerate kinase, has been mapped to 2-5.9; cytogenetically it was found to lie in the interval between 22D and 23E3. The cytogenetic locataion of Pgm, the structural gene for phosphoglucomutase which has been located genetically at 3-43.4, was determined to be in 72D1-5.", "contents": "Genetic and cytogenetic studies of four glycolytic enzymes in Drosophila melanogaster: aldolase, triosephosphate isomerase, 3-phosphoglycerate kinase, and phosphoglucomutase. Four glycolytic enzymes in Drosophila melanogaster have been genetically and/or cytogenetically mapped. The structural gene for aldolase (Ald) has been genetically mapped to 3-91.5 and cytogenetically localized to 97A-B. Tpi, the structural gene for triosephosphate isomerase, has been genetically mapped to 3-101.3 and cytogenetically localized to 99B-E. Utilizing closer-flanking markers than the previous mapping, Pgk, the structural gene for 3-phosphoglycerate kinase, has been mapped to 2-5.9; cytogenetically it was found to lie in the interval between 22D and 23E3. The cytogenetic locataion of Pgm, the structural gene for phosphoglucomutase which has been located genetically at 3-43.4, was determined to be in 72D1-5."} {"id": "PMID:161507", "title": "A new fluorogenic substrate for plasmin.", "content": "A new fluorogenic peptide substrate for plasmin, 7-(N-succinoylalanylphenylalanyl-lysylamido)-4-methylcoumarin trifluoroacetate salt, was prepared that can be used in a simple and direct assay. The results obtained by the assay method are linear over a wide range of enzyme concentrations and sensitive enough to detect as little as 10(-5) CTA units of plasmin. By making use of the inhibitor Trasylol and the differences in kinetic constants, plasmin can be specifically assayed even in the presence of the plasminogen activator thrombin, as well as in culture fluids from HeLa cells.", "contents": "A new fluorogenic substrate for plasmin. A new fluorogenic peptide substrate for plasmin, 7-(N-succinoylalanylphenylalanyl-lysylamido)-4-methylcoumarin trifluoroacetate salt, was prepared that can be used in a simple and direct assay. The results obtained by the assay method are linear over a wide range of enzyme concentrations and sensitive enough to detect as little as 10(-5) CTA units of plasmin. By making use of the inhibitor Trasylol and the differences in kinetic constants, plasmin can be specifically assayed even in the presence of the plasminogen activator thrombin, as well as in culture fluids from HeLa cells."} {"id": "PMID:161508", "title": "Structure of heparan sulphate oligosaccharides and their degradation by exo-enzymes.", "content": "Oligosaccharides obtained from heparan sulphate by nitrous acid degradation were shown to be degraded sequentially by beta-D-glucuronidase or alpha-L-iduronidase followed by alpha D-N-acetylglucosaminidase. Structural analysis of the tetrasaccharide fraction showed the following. (1) N-Acetylglucosamine is preceded by a non-sulphated uronic acid residue that can be either D-glucuronic of L-iduronic acid, but followed by a glucuronic acid residue. (2) The N-acetylglucosamine in the major fraction is sulphated. (3) Very few if any of the uronic acid residues are sulphated (4). The results indicate that the area of the heparan sulphate chain where disaccharides containing N-acetylglucosamine and N-sulphated glucosamine residues alternate is higher in sulphate content than expected and that the sulphate groups are mainly located on the hexosamine units.", "contents": "Structure of heparan sulphate oligosaccharides and their degradation by exo-enzymes. Oligosaccharides obtained from heparan sulphate by nitrous acid degradation were shown to be degraded sequentially by beta-D-glucuronidase or alpha-L-iduronidase followed by alpha D-N-acetylglucosaminidase. Structural analysis of the tetrasaccharide fraction showed the following. (1) N-Acetylglucosamine is preceded by a non-sulphated uronic acid residue that can be either D-glucuronic of L-iduronic acid, but followed by a glucuronic acid residue. (2) The N-acetylglucosamine in the major fraction is sulphated. (3) Very few if any of the uronic acid residues are sulphated (4). The results indicate that the area of the heparan sulphate chain where disaccharides containing N-acetylglucosamine and N-sulphated glucosamine residues alternate is higher in sulphate content than expected and that the sulphate groups are mainly located on the hexosamine units."} {"id": "PMID:161509", "title": "Dissociation and reassociation of rabbit skeletal muscle myosin.", "content": "Whereas dissociation of rabbit skeletal muscle myosin light chains occurs at an increased temperature (25 degrees) and in the absence of divalent cations, reassociation of the myosin oligomer requires a low temperature (4 degrees C) and the presence of divalent cations, thus resulting in the original light to heavy chain stoichiometry. With a 5-10 per cent release of alkali light chains, LC1 and LC3, and a 50 per cent dissociation of the Ca2+ binding light chain, LC2, there is no significant decrease in myosin ATPase activity irrespective of the cation activator, however, there is an approximate 15-20 per cent decrease in actomyosin ATPase activity. With reassociation of the myosin oligomer, actomyosin ATPase activity is partially restored as well as the original number of Ca2+ binding sites.", "contents": "Dissociation and reassociation of rabbit skeletal muscle myosin. Whereas dissociation of rabbit skeletal muscle myosin light chains occurs at an increased temperature (25 degrees) and in the absence of divalent cations, reassociation of the myosin oligomer requires a low temperature (4 degrees C) and the presence of divalent cations, thus resulting in the original light to heavy chain stoichiometry. With a 5-10 per cent release of alkali light chains, LC1 and LC3, and a 50 per cent dissociation of the Ca2+ binding light chain, LC2, there is no significant decrease in myosin ATPase activity irrespective of the cation activator, however, there is an approximate 15-20 per cent decrease in actomyosin ATPase activity. With reassociation of the myosin oligomer, actomyosin ATPase activity is partially restored as well as the original number of Ca2+ binding sites."} {"id": "PMID:161510", "title": "Differential toxicities of mercury to bacteria and bacteriophages in sea and in lake water.", "content": "Mixtures of anionic HgCl3-/HgCl4(2)-complexes were less toxic to terrestrial bacteria (Erwinia herbicola, Agrobacterium tumefaciens), to marine bacteria (Acinetobacter sp., Aeromonas sp.), and to bacteriophages (phi 11 M 15 of Staphylococcus aureus and P1 of Escherichia coli) than were equivalent concentrations of Hg as cationic Hg2+. The toxicity of 1 ppm Hg to A. tumefaciens. Aeromonas sp., and phi 11 M 15 was less in seawater than in lake water. Inasmuch as the Hg-Cl species are formed in environments of high chloride concentration, it was postulated that the lower toxicity of Hg in seawater was a result of the formation of HgCl3-/HgCl4(2)-complexes.", "contents": "Differential toxicities of mercury to bacteria and bacteriophages in sea and in lake water. Mixtures of anionic HgCl3-/HgCl4(2)-complexes were less toxic to terrestrial bacteria (Erwinia herbicola, Agrobacterium tumefaciens), to marine bacteria (Acinetobacter sp., Aeromonas sp.), and to bacteriophages (phi 11 M 15 of Staphylococcus aureus and P1 of Escherichia coli) than were equivalent concentrations of Hg as cationic Hg2+. The toxicity of 1 ppm Hg to A. tumefaciens. Aeromonas sp., and phi 11 M 15 was less in seawater than in lake water. Inasmuch as the Hg-Cl species are formed in environments of high chloride concentration, it was postulated that the lower toxicity of Hg in seawater was a result of the formation of HgCl3-/HgCl4(2)-complexes."} {"id": "PMID:161522", "title": "Guinea worm disease: epidemiology, control, and treatment.", "content": "Guinea worm infection is one of the most easily prevented parasitic diseases, but it is nevertheless a common cause of disability in rural areas of Africa, south-west Asia, and India. Infection occurs when drinking water is infested with infected Cyclops, a microcrustacean. Worms up to 70-80 cm in length develop in the subcutaneous tissues of the feet or legs and larvae are liberated to renew the cycle when an infected individual steps into a well or pond from which others draw drinking water. Infection is markedly seasonal because of (a) the influence of the climate on the types of water source used and (b) the developmental cycle of the parasite. The disability may be economically very important if the period of infection coincides with busy periods in the agricultural year. Sieving water through a cloth is sufficient to remove the Cyclops, but on a public health scale improved water supplies are required for control. Once the cycle of reinfection can be broken in any district the disease disappears. Chemical treatment of water bodies with temephos is also an effective and safe way of controlling transmission. Treatment consists of rolling out each emerging worm onto a small stick, a few centimetres each day, and certain drugs reduce the pain and pruritus and enable the worm to be removed more quickly.", "contents": "Guinea worm disease: epidemiology, control, and treatment. Guinea worm infection is one of the most easily prevented parasitic diseases, but it is nevertheless a common cause of disability in rural areas of Africa, south-west Asia, and India. Infection occurs when drinking water is infested with infected Cyclops, a microcrustacean. Worms up to 70-80 cm in length develop in the subcutaneous tissues of the feet or legs and larvae are liberated to renew the cycle when an infected individual steps into a well or pond from which others draw drinking water. Infection is markedly seasonal because of (a) the influence of the climate on the types of water source used and (b) the developmental cycle of the parasite. The disability may be economically very important if the period of infection coincides with busy periods in the agricultural year. Sieving water through a cloth is sufficient to remove the Cyclops, but on a public health scale improved water supplies are required for control. Once the cycle of reinfection can be broken in any district the disease disappears. Chemical treatment of water bodies with temephos is also an effective and safe way of controlling transmission. Treatment consists of rolling out each emerging worm onto a small stick, a few centimetres each day, and certain drugs reduce the pain and pruritus and enable the worm to be removed more quickly."} {"id": "PMID:161529", "title": "Dermatological aspects of so called vinyl chloride monomer disease.", "content": "The pathological findings revealed in 30 subjects with so called vinyl chloride disease has been presented. The most often observed symptoms were: changes in histopathological picture of the skin, history of the symptoms of Raynaud's phenomenon, positive results of functional proofs (pletysmography, vibration perception test, cooling test), and scleroderma like skin lesions. Acroosteolysis was found only in 3 cases, thrombocytopenia only in one. The constellation of singns may be related to the high level of exposure of examined persons. The authors point to the significance of dermatological methods of investigation for detection of morbid changes induced by VCM action.", "contents": "Dermatological aspects of so called vinyl chloride monomer disease. The pathological findings revealed in 30 subjects with so called vinyl chloride disease has been presented. The most often observed symptoms were: changes in histopathological picture of the skin, history of the symptoms of Raynaud's phenomenon, positive results of functional proofs (pletysmography, vibration perception test, cooling test), and scleroderma like skin lesions. Acroosteolysis was found only in 3 cases, thrombocytopenia only in one. The constellation of singns may be related to the high level of exposure of examined persons. The authors point to the significance of dermatological methods of investigation for detection of morbid changes induced by VCM action."} {"id": "PMID:161530", "title": "Occupational dermatitis among health service workers.", "content": "Health service workers in the number of 152 suffering of dermatitis were examined. They included 43 physicians, 25 stomatologists, 59 nurses, 14 hospital-wards and 12 other persons working in hospitals, clinics and pharmacies. In physicians occupational contact dermatitis occured in ten patients, exclusively among those performing operations, most frequently surgeons and ginecologists. Rubber gloves (5 patients) disinfectants and chromic catgut were the sensitizing objects. Moreover, a woman gynecologist positive to nickel observed that also the use of a speculum exacerbated her lesions. A laryngologist with seborrhoic dermatitis, strongly positive to formaldehyde, had exacerbations when using--during surgery--a microscope disinfected with formalin solution. Allergic occupational contact dermatitis was diagnosed in 12 stomatologists; they were positive to eugenol, mercury, novocaine or formaldehyde. Among 24 nurses with allergic occupational contact dermatitis, those positive to antibiotics (specially to semisynthetic penicillins) or to disinfectants (most of them to formaldehyde) were most numerous. Some nurses were sensitive to such drugs as Propranolol, Aminophyllinum or chlorpromazine hydrochloride. To the latter drug also a ward attendant was positive.", "contents": "Occupational dermatitis among health service workers. Health service workers in the number of 152 suffering of dermatitis were examined. They included 43 physicians, 25 stomatologists, 59 nurses, 14 hospital-wards and 12 other persons working in hospitals, clinics and pharmacies. In physicians occupational contact dermatitis occured in ten patients, exclusively among those performing operations, most frequently surgeons and ginecologists. Rubber gloves (5 patients) disinfectants and chromic catgut were the sensitizing objects. Moreover, a woman gynecologist positive to nickel observed that also the use of a speculum exacerbated her lesions. A laryngologist with seborrhoic dermatitis, strongly positive to formaldehyde, had exacerbations when using--during surgery--a microscope disinfected with formalin solution. Allergic occupational contact dermatitis was diagnosed in 12 stomatologists; they were positive to eugenol, mercury, novocaine or formaldehyde. Among 24 nurses with allergic occupational contact dermatitis, those positive to antibiotics (specially to semisynthetic penicillins) or to disinfectants (most of them to formaldehyde) were most numerous. Some nurses were sensitive to such drugs as Propranolol, Aminophyllinum or chlorpromazine hydrochloride. To the latter drug also a ward attendant was positive."} {"id": "PMID:161531", "title": "[Vitiligo from p-tert. butylphenol; a contribution to the problem of the internal manifestations of this occupational disease].", "content": "10 worker suffering from occupational vitiligo due to p-tert. butyl phenol have been observed in an Austrian resin factory. The dust concentration and its content of p-tert. butyl phenol in the working area were measured. On the basis of these results preventive measures were taken to reduce the exposure of the workers to p-test butyl phenol. In the presented cases an involvement of internal organs--as described by Rodermund et al. (1975)--could not be observed.", "contents": "[Vitiligo from p-tert. butylphenol; a contribution to the problem of the internal manifestations of this occupational disease]. 10 worker suffering from occupational vitiligo due to p-tert. butyl phenol have been observed in an Austrian resin factory. The dust concentration and its content of p-tert. butyl phenol in the working area were measured. On the basis of these results preventive measures were taken to reduce the exposure of the workers to p-test butyl phenol. In the presented cases an involvement of internal organs--as described by Rodermund et al. (1975)--could not be observed."} {"id": "PMID:161534", "title": "[The left ventricle in chronic renal failure patients. Ecocardiographic and poligraphic study before and after hemodialysis (author's transl)].", "content": "Echocardiographic and systolic time intervals changes found after hemodyalisis in 16 patients with chronic renal failure are analysed and discussed. Echocardiogram shows: significant (p less than 0.05), no change statistically significant of end-systolic diameter, fractional shortening, mean velocity of circumferential shortening (VcF), and amplitude of septal motion. Systolic time intervals show: significant reduction (p less than 0.001) of total electromechanical systole (SEM), mechanical systole (SM) and left ventricular ejection time (LVET), and increase (p less than 0.05) of pre-ejection period (PEP) and the ratio PEP/LVET (p less than 0.005). The reason of these changes is the post-dialytic fluid's loss (2140 +/- 760 g) followed by left ventricular end-diastolic diameter and volume reduction which decreases stoke volume and LVET (according to Frank-Starling's law). It has not been possible to draw concordant and definitive conclusions on the post-dialytic left ventricular function. PEP lengthening would give evident for myocardial involvement (but pre-load and after-load changes modifies it), while the other data are slightly affected (VcF, fractional shortening, and amplitude of septal motion) or improved (amplitude and peak velocity of posterior wall motion).", "contents": "[The left ventricle in chronic renal failure patients. Ecocardiographic and poligraphic study before and after hemodialysis (author's transl)]. Echocardiographic and systolic time intervals changes found after hemodyalisis in 16 patients with chronic renal failure are analysed and discussed. Echocardiogram shows: significant (p less than 0.05), no change statistically significant of end-systolic diameter, fractional shortening, mean velocity of circumferential shortening (VcF), and amplitude of septal motion. Systolic time intervals show: significant reduction (p less than 0.001) of total electromechanical systole (SEM), mechanical systole (SM) and left ventricular ejection time (LVET), and increase (p less than 0.05) of pre-ejection period (PEP) and the ratio PEP/LVET (p less than 0.005). The reason of these changes is the post-dialytic fluid's loss (2140 +/- 760 g) followed by left ventricular end-diastolic diameter and volume reduction which decreases stoke volume and LVET (according to Frank-Starling's law). It has not been possible to draw concordant and definitive conclusions on the post-dialytic left ventricular function. PEP lengthening would give evident for myocardial involvement (but pre-load and after-load changes modifies it), while the other data are slightly affected (VcF, fractional shortening, and amplitude of septal motion) or improved (amplitude and peak velocity of posterior wall motion)."} {"id": "PMID:161544", "title": "Histochemistry of gland cells of Eurytrema pancreaticum cercariae.", "content": "The cercariae of Eurytrema pancreaticum (Janson, 1889) possess four types of gland cells - proper cystogenic, penetration, ventral and dorsal gland cells. The secretion of ventral and dorsal gland cells is released into the tegument. The proper cystogenic gland cells are the largest and their contents serve for the formation of the cyst wall of metacercariae in the second intermediate host. The secretion of proper cystogenic gland cells contains besides neutral mucosubstances also acid mucosubstances with both carboxyl- and sulphogroups digestible with beta-glucuronidase. The secretion of penetration gland cells contains neutral mucosubstances and proteins with tyrosine, tryptophan and SS groups. The ventral gland cells contain mostly acid mucosubstances with sulphogroups, which are digested with beta-glucuronidase, and proteins with tyrosine, tryptophan and SH groups. The rudimentary dorsal gland cells contain a small amount of acid mucosubstances. The whole tegument of cercariae and the two main collecting canals of the excretory system exhibit a high alkaline phosphatase activity. The nerve ring and the main nerve truncs contain proteins with SH groups and hydrophilic lipids and exhibit a cholinesterase activity. The suckers contain a larger amount of glycogen.", "contents": "Histochemistry of gland cells of Eurytrema pancreaticum cercariae. The cercariae of Eurytrema pancreaticum (Janson, 1889) possess four types of gland cells - proper cystogenic, penetration, ventral and dorsal gland cells. The secretion of ventral and dorsal gland cells is released into the tegument. The proper cystogenic gland cells are the largest and their contents serve for the formation of the cyst wall of metacercariae in the second intermediate host. The secretion of proper cystogenic gland cells contains besides neutral mucosubstances also acid mucosubstances with both carboxyl- and sulphogroups digestible with beta-glucuronidase. The secretion of penetration gland cells contains neutral mucosubstances and proteins with tyrosine, tryptophan and SS groups. The ventral gland cells contain mostly acid mucosubstances with sulphogroups, which are digested with beta-glucuronidase, and proteins with tyrosine, tryptophan and SH groups. The rudimentary dorsal gland cells contain a small amount of acid mucosubstances. The whole tegument of cercariae and the two main collecting canals of the excretory system exhibit a high alkaline phosphatase activity. The nerve ring and the main nerve truncs contain proteins with SH groups and hydrophilic lipids and exhibit a cholinesterase activity. The suckers contain a larger amount of glycogen."} {"id": "PMID:161545", "title": "[Pharmacological studies on experimental nephritic rats (6). Antinephritic effects of sodium chondroitin sulfate and other drugs on modified type of Masugi's nephritis].", "content": "Using the modified model of Masugi's nephritis in rats, the antinephritic effects of sodium chondroitin sulfate (CS) and other drugs were evaluated by determining the biochemical parameters in urine, serum and renal cortex as well as light microscopic observation in kidneys by preventive and curative tests. In the preventive test where drug treatment was initiated at the same time as the injection of anti-kidney serum, CS (200 mg/kg p.o.) was effective in reducing serum triglyceride level, but was ineffective against other parameters. In the curative test where drug treatment was given from the 10th day after the induction of nephritis, CS (200 mg/kg p.o.) resulted in reductions of urinary excretions of protein and enzymes such as alkaline phosphatase and N-acetyl-beta-glucosaminidase, the inhibition of urinary fibrinolytic activity and reduction in levels of serum cholesterol and triglyceride. Moreover, histological examination indicated a significant reduction of the index of glomerular lesions by the treatment of this drug. Of other drugs, dexamethasone (0.1 mg/kg p.o.) was effective in both tests, while warfarin potassium (0.05 or 0.1 mg/kg p.o.) exerted a beneficial effect only in the preventive test. From these results, the effectiveness of CS in the curative test is probably due to promotion of healing of damaged tissue in the kidneys.", "contents": "[Pharmacological studies on experimental nephritic rats (6). Antinephritic effects of sodium chondroitin sulfate and other drugs on modified type of Masugi's nephritis]. Using the modified model of Masugi's nephritis in rats, the antinephritic effects of sodium chondroitin sulfate (CS) and other drugs were evaluated by determining the biochemical parameters in urine, serum and renal cortex as well as light microscopic observation in kidneys by preventive and curative tests. In the preventive test where drug treatment was initiated at the same time as the injection of anti-kidney serum, CS (200 mg/kg p.o.) was effective in reducing serum triglyceride level, but was ineffective against other parameters. In the curative test where drug treatment was given from the 10th day after the induction of nephritis, CS (200 mg/kg p.o.) resulted in reductions of urinary excretions of protein and enzymes such as alkaline phosphatase and N-acetyl-beta-glucosaminidase, the inhibition of urinary fibrinolytic activity and reduction in levels of serum cholesterol and triglyceride. Moreover, histological examination indicated a significant reduction of the index of glomerular lesions by the treatment of this drug. Of other drugs, dexamethasone (0.1 mg/kg p.o.) was effective in both tests, while warfarin potassium (0.05 or 0.1 mg/kg p.o.) exerted a beneficial effect only in the preventive test. From these results, the effectiveness of CS in the curative test is probably due to promotion of healing of damaged tissue in the kidneys."} {"id": "PMID:161546", "title": "[Immunopharmacological study of buckwheat hypersensitivity III. Effect of dialysate-conjugated T cell mitogen on IgE formation (author's transl)].", "content": "It has already been reported that dialysate (BWD) separated from the aqueous extract of buckwheat is a haptenic substance capable of neutralizing specific IgE antibody both on mast cells and on B cells in some species. The present work represents a study carried out to determine the effect of BWD conjugated with T cell mitogen such as phyothemagglutinin-P (PHA) and concanavalin A (Con A) on IgE formation in mice. Anti-buckwheat IgE formation was little affected by the pretreatment of these conjugates given i.v. 3 days before the immunization, but was effectively suppressed by the pretreatment of BWD-PHA or BWD-Con A given i.p. together with incomplete Freund's adjuvant 2 weeks before the immunization. BWD-PHA induced a more potent suppression of IgE formation as compared with BWD-Con A, Con A or PHA. The transfer of T cells obtained from spleen cells primed with BWD-PHA, which responded with buckwheat and exerted a slight helper function for adoptive anti-DNP IgE formation to DNP-buckwheat, suppressed anti-buckwheat IgE formation in recipients with no effect on the anti-KLH IgE response. Our findings suggest that suppressor T cells specific to buckwheat are induced in spleen cells of mice treated with BWD-PHA.", "contents": "[Immunopharmacological study of buckwheat hypersensitivity III. Effect of dialysate-conjugated T cell mitogen on IgE formation (author's transl)]. It has already been reported that dialysate (BWD) separated from the aqueous extract of buckwheat is a haptenic substance capable of neutralizing specific IgE antibody both on mast cells and on B cells in some species. The present work represents a study carried out to determine the effect of BWD conjugated with T cell mitogen such as phyothemagglutinin-P (PHA) and concanavalin A (Con A) on IgE formation in mice. Anti-buckwheat IgE formation was little affected by the pretreatment of these conjugates given i.v. 3 days before the immunization, but was effectively suppressed by the pretreatment of BWD-PHA or BWD-Con A given i.p. together with incomplete Freund's adjuvant 2 weeks before the immunization. BWD-PHA induced a more potent suppression of IgE formation as compared with BWD-Con A, Con A or PHA. The transfer of T cells obtained from spleen cells primed with BWD-PHA, which responded with buckwheat and exerted a slight helper function for adoptive anti-DNP IgE formation to DNP-buckwheat, suppressed anti-buckwheat IgE formation in recipients with no effect on the anti-KLH IgE response. Our findings suggest that suppressor T cells specific to buckwheat are induced in spleen cells of mice treated with BWD-PHA."} {"id": "PMID:161557", "title": "Ecological aspects concerning the rehabilitation of handicapped persons.", "content": "When drawing up demand-oriented plans and establishing a network of rehabilitation facilities covering all areas, it is advisable to make an ecological analysis of the area to be served. Such an analysis should take into account the natural physical and socio-geographical conditions as well as basic data relating to the population living in a particular area and its movement. A further step is the topographical determination of available data on chronic diseases and handicaps in the individual discernable areas; besides the various statistical data, one should investigate also the degree of severity and the care required by the individual forms of diseases or handicaps. These factors largely influence the needs in the fields of medical, educational, vocational and social rehabilitation for in-patient or out-patient facilities and the personnel requirements in the form of specialist staff. When performing such calculations, it is often necessary to find a compromise between the various alternatives in accordance with the corresponding, existing socio-political and national health system. On the basis of such data, it is possible to formulate a concrete single plan together with already functioning institutions; such a plan could take its lead from a model concept. Of assistance, in this case, would be an epidemiological assessment which , in a longitudinal section of time, can transform itself into interventionist research and improvement of the deficiencies thereby ascertained. Consideration should also be paid to allowing future actions to be accompanied by scientific measures.", "contents": "Ecological aspects concerning the rehabilitation of handicapped persons. When drawing up demand-oriented plans and establishing a network of rehabilitation facilities covering all areas, it is advisable to make an ecological analysis of the area to be served. Such an analysis should take into account the natural physical and socio-geographical conditions as well as basic data relating to the population living in a particular area and its movement. A further step is the topographical determination of available data on chronic diseases and handicaps in the individual discernable areas; besides the various statistical data, one should investigate also the degree of severity and the care required by the individual forms of diseases or handicaps. These factors largely influence the needs in the fields of medical, educational, vocational and social rehabilitation for in-patient or out-patient facilities and the personnel requirements in the form of specialist staff. When performing such calculations, it is often necessary to find a compromise between the various alternatives in accordance with the corresponding, existing socio-political and national health system. On the basis of such data, it is possible to formulate a concrete single plan together with already functioning institutions; such a plan could take its lead from a model concept. Of assistance, in this case, would be an epidemiological assessment which , in a longitudinal section of time, can transform itself into interventionist research and improvement of the deficiencies thereby ascertained. Consideration should also be paid to allowing future actions to be accompanied by scientific measures."} {"id": "PMID:161558", "title": "Healing of the operative fascial defect after repair of huge midline hernias with the reverse sheath method.", "content": "An experiment was carried out to ascertain the fate of the bared muscle following the repair of huge midline hernias with the \"reverse sheath\" method. Thirty-five patients have undergone operation by this method over the past five years, with excellent results. Experimental stripping of abdominal fascia was done on 35 rats. The bare rectus muscle was examined 1, 3, 5, 8 and 11 months after the operation. No regeneration of fascia was seen. The missing fascia was replaced by scar tissue. The results are important with regard to the support of the abdominal wall after repair of midline abdominal hernia by the above-mentioned method.", "contents": "Healing of the operative fascial defect after repair of huge midline hernias with the reverse sheath method. An experiment was carried out to ascertain the fate of the bared muscle following the repair of huge midline hernias with the \"reverse sheath\" method. Thirty-five patients have undergone operation by this method over the past five years, with excellent results. Experimental stripping of abdominal fascia was done on 35 rats. The bare rectus muscle was examined 1, 3, 5, 8 and 11 months after the operation. No regeneration of fascia was seen. The missing fascia was replaced by scar tissue. The results are important with regard to the support of the abdominal wall after repair of midline abdominal hernia by the above-mentioned method."} {"id": "PMID:161552", "title": "Regional myocyte size in normotensive and spontaneously hypertensive rats.", "content": "Regional differences in cell size in the hearts of rats with and without cardiac hypertrophy were studied using isolated muscle cells. Isolated cardiac myocytes were prepared from left ventricular free wall inner and outer halves and the right ventricle of six male 12-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Fischer-344 rats. In SHR, blood pressure was increased to 188 +/- 4 (SEM) mm Hg versus 143 +/- 2 and 133 +/- 10 for WKY and Fischer rats, respectively (p less than 0.001). Total heart weight was increased to 1103 +/- 29 mg in SHR compared to 824 +/- 21 in WKY and 951 +/- 23 in Fischer rats (p less than 0.001. Isolated cardiac myocytes were prepared by perfusion of isolated hearts with Ca++ free Hanks' solution containing EGTA followed by collagenase-containing media. Mean length, width and volume of 150 cells stained with hematoxylin and eosin from each site were measured with a sonic digitizer. Two nuclei were present in 85 to 87% of isolated cells from all strains and regions. There was no difference among strains in right ventricular cell length, width, or volume, nor between left ventricular inner and outer halves within each strain. Left ventricular cells were larger than right ventricular cells (p less than 0.05) in all strains. Left ventricular cells of SHR were larger than left ventricular cells of WKY of Fischer rats in proportion to the increase in total heart weight, indicating that cardiac enlargement in SHR is due to increased cell size rather than increased cell number.", "contents": "Regional myocyte size in normotensive and spontaneously hypertensive rats. Regional differences in cell size in the hearts of rats with and without cardiac hypertrophy were studied using isolated muscle cells. Isolated cardiac myocytes were prepared from left ventricular free wall inner and outer halves and the right ventricle of six male 12-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Fischer-344 rats. In SHR, blood pressure was increased to 188 +/- 4 (SEM) mm Hg versus 143 +/- 2 and 133 +/- 10 for WKY and Fischer rats, respectively (p less than 0.001). Total heart weight was increased to 1103 +/- 29 mg in SHR compared to 824 +/- 21 in WKY and 951 +/- 23 in Fischer rats (p less than 0.001. Isolated cardiac myocytes were prepared by perfusion of isolated hearts with Ca++ free Hanks' solution containing EGTA followed by collagenase-containing media. Mean length, width and volume of 150 cells stained with hematoxylin and eosin from each site were measured with a sonic digitizer. Two nuclei were present in 85 to 87% of isolated cells from all strains and regions. There was no difference among strains in right ventricular cell length, width, or volume, nor between left ventricular inner and outer halves within each strain. Left ventricular cells were larger than right ventricular cells (p less than 0.05) in all strains. Left ventricular cells of SHR were larger than left ventricular cells of WKY of Fischer rats in proportion to the increase in total heart weight, indicating that cardiac enlargement in SHR is due to increased cell size rather than increased cell number."} {"id": "PMID:161554", "title": "Association of blood groups with essential and secondary hypertension. A possible association of the MNS system.", "content": "Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobin, phosphoglucomutase-1 (PGM-1), and acid phosphatase (AcP). The study population was composed of 164 normotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic renovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phenotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with normotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X2 = 12.21, p less than 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X 2 = 4.34, p less than 0.05) and Ss (X2 = 4.21, p less than 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types.", "contents": "Association of blood groups with essential and secondary hypertension. A possible association of the MNS system. Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobin, phosphoglucomutase-1 (PGM-1), and acid phosphatase (AcP). The study population was composed of 164 normotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic renovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phenotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with normotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X2 = 12.21, p less than 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X 2 = 4.34, p less than 0.05) and Ss (X2 = 4.21, p less than 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types."} {"id": "PMID:161560", "title": "[Neonatal thrombocyte values in children with Down's syndrome and other autosome trisomies].", "content": "Platelet counts were determined in 70 neonates with trisomy-21, 10 neonates with trisomy-18 and 6 neonates with trisomy-13 during the first days of life. 60% of all infants with trisomy-aberrations were found to have thrombocytopenia. Platelet counts in Down's syndrome averaged 104600 (SD 53000; median 90500; 10- and 90-percentile at 45000 and 175000) per microliter. A correlation with other hematological features of trisomy-21 was examined. There was no significant correlation between platelet counts and hemoglobin concentration. Similarly the difference in platelet counts between trisomy-neonates with and without polycythemia was statistically not significant. In contrast, 27 normal neonates with polycythemia showed significantly higher platelet counts (mean = 13400) than their trisomy-counterparts (mean = 98900; P = 0.01). In addition, there was no correlation, in trisomy infants, between either erythroblastosis or low birth weight and platelet count. These findings point to defective hematopoiesis as a primary cause of thrombocytopenia in trisomy-infants.", "contents": "[Neonatal thrombocyte values in children with Down's syndrome and other autosome trisomies]. Platelet counts were determined in 70 neonates with trisomy-21, 10 neonates with trisomy-18 and 6 neonates with trisomy-13 during the first days of life. 60% of all infants with trisomy-aberrations were found to have thrombocytopenia. Platelet counts in Down's syndrome averaged 104600 (SD 53000; median 90500; 10- and 90-percentile at 45000 and 175000) per microliter. A correlation with other hematological features of trisomy-21 was examined. There was no significant correlation between platelet counts and hemoglobin concentration. Similarly the difference in platelet counts between trisomy-neonates with and without polycythemia was statistically not significant. In contrast, 27 normal neonates with polycythemia showed significantly higher platelet counts (mean = 13400) than their trisomy-counterparts (mean = 98900; P = 0.01). In addition, there was no correlation, in trisomy infants, between either erythroblastosis or low birth weight and platelet count. These findings point to defective hematopoiesis as a primary cause of thrombocytopenia in trisomy-infants."} {"id": "PMID:161561", "title": "Allometric radial growth in muscle, comparing fibres with strong and with weak adenosine triphosphatase activity.", "content": "A large flock of male and female white turkeys (Meleagris gallopavo) was reared for 22 weeks after hatching. At two weeks intervals small groups of birds were removed from the flock and killed. Samples of sartorius muscles were taken from the bird nearest the mean weight for its group. Transverse frozen sections were tested for ATPase activity by calcium method at pH 9.4. Fibres were separated into two categories (strong-ATPase and weak-ATPase) and their mean minimum diameters were measured with a micrometer scale in the microscope eyepiece. Mean minimum diameters of different fibre types were compared using the logarithmic form of Huxley's allometric growth equation. Weak-ATPase fibres grew at a relatively faster rate than strong-ATPase fibres in both males and females (k = 1.12, P less than 0.01 and k = 1.14, P less than 0.01 respectively). Transition of muscle fibres from one histochemical type to another was not detected, so that differences in the rate of increase of mean diameters of different fibre types were attributed to allometric radial growth. The possibility that transitional fibres might make some contribution cannot, however, be totally ignored.", "contents": "Allometric radial growth in muscle, comparing fibres with strong and with weak adenosine triphosphatase activity. A large flock of male and female white turkeys (Meleagris gallopavo) was reared for 22 weeks after hatching. At two weeks intervals small groups of birds were removed from the flock and killed. Samples of sartorius muscles were taken from the bird nearest the mean weight for its group. Transverse frozen sections were tested for ATPase activity by calcium method at pH 9.4. Fibres were separated into two categories (strong-ATPase and weak-ATPase) and their mean minimum diameters were measured with a micrometer scale in the microscope eyepiece. Mean minimum diameters of different fibre types were compared using the logarithmic form of Huxley's allometric growth equation. Weak-ATPase fibres grew at a relatively faster rate than strong-ATPase fibres in both males and females (k = 1.12, P less than 0.01 and k = 1.14, P less than 0.01 respectively). Transition of muscle fibres from one histochemical type to another was not detected, so that differences in the rate of increase of mean diameters of different fibre types were attributed to allometric radial growth. The possibility that transitional fibres might make some contribution cannot, however, be totally ignored."} {"id": "PMID:161563", "title": "[Laparoscopic treatment of stenoses and phimosis of the ampulla of the tube. A critical study of the results (author's transl)].", "content": "By analysing a series that initially started with 160 cases it is possible to compare the results of trying to cure infundibular stenoses, which means agglutinations and phimosis of the ampulla using the laparoscope or open laparotomy. It would appear that these lesions should be strictly classified and this classification should be based on careful laparoscopic investigation of the infundibulum and on hydrotubation testing. It is then found that these are not good cases for endoscopic surgical treatment. The results are poor whether looked at from the level of fertility that is finally achieved as well as the morphological improvement in the conditions and they are far worse than those following conventional surgery. Therefore it is necessary to conclude that laparotomy is always preferable for a cure of these cases. The only indication for laparoscopic surgery is infundibular stenosis which occurs afterterminal tubal plastic surgery which is by itself not a rare happening.", "contents": "[Laparoscopic treatment of stenoses and phimosis of the ampulla of the tube. A critical study of the results (author's transl)]. By analysing a series that initially started with 160 cases it is possible to compare the results of trying to cure infundibular stenoses, which means agglutinations and phimosis of the ampulla using the laparoscope or open laparotomy. It would appear that these lesions should be strictly classified and this classification should be based on careful laparoscopic investigation of the infundibulum and on hydrotubation testing. It is then found that these are not good cases for endoscopic surgical treatment. The results are poor whether looked at from the level of fertility that is finally achieved as well as the morphological improvement in the conditions and they are far worse than those following conventional surgery. Therefore it is necessary to conclude that laparotomy is always preferable for a cure of these cases. The only indication for laparoscopic surgery is infundibular stenosis which occurs afterterminal tubal plastic surgery which is by itself not a rare happening."} {"id": "PMID:161564", "title": "[Prevention of recurring adhesions after tuboplasties. I--Interest of early laparoscopy, 8 days after surgery (author's transl)].", "content": "Laparoscopy was performed 8 days after tuboplasty in 80 cases. In 32 cases, new fresh adhesions were swept out with a rod on the 8th day. These adhesions were important in 13 cases (16,2 p. 100). This treatment seems to be efficient.", "contents": "[Prevention of recurring adhesions after tuboplasties. I--Interest of early laparoscopy, 8 days after surgery (author's transl)]. Laparoscopy was performed 8 days after tuboplasty in 80 cases. In 32 cases, new fresh adhesions were swept out with a rod on the 8th day. These adhesions were important in 13 cases (16,2 p. 100). This treatment seems to be efficient."} {"id": "PMID:161570", "title": "An improved means of enzyme typing of hair roots using isoelectric focusing.", "content": "An improved method of grouping hair, based on the alleles of PGM observed by isoelectric focusing, has been described. The increased discriminating power of this system (0.77) compared to that obtained by the starch gel technique (0.55) provides a new and more sensitive means of typing hair.", "contents": "An improved means of enzyme typing of hair roots using isoelectric focusing. An improved method of grouping hair, based on the alleles of PGM observed by isoelectric focusing, has been described. The increased discriminating power of this system (0.77) compared to that obtained by the starch gel technique (0.55) provides a new and more sensitive means of typing hair."} {"id": "PMID:161572", "title": "Complementation analysis of eleven tryptophanase mutations in Escherichia coli.", "content": "Nine independent mutants deficient in tryptophanase activity were isolated. Each mutation was transferred to a specialized transducing phage that carries the tryptophanase region of the Escherichia coli chromosome. The nine phages thus produced, and a tenth carrying a previously characterized tryptophanase mutation, were used to lysogenize a bacterial strain harbouring a mutation in the tryptophanase structural gene and also a suppressor of polarity. In no case was complementation observed; we conclude that there is no closely linked positive regulatory gene for tryptophanase.", "contents": "Complementation analysis of eleven tryptophanase mutations in Escherichia coli. Nine independent mutants deficient in tryptophanase activity were isolated. Each mutation was transferred to a specialized transducing phage that carries the tryptophanase region of the Escherichia coli chromosome. The nine phages thus produced, and a tenth carrying a previously characterized tryptophanase mutation, were used to lysogenize a bacterial strain harbouring a mutation in the tryptophanase structural gene and also a suppressor of polarity. In no case was complementation observed; we conclude that there is no closely linked positive regulatory gene for tryptophanase."} {"id": "PMID:161573", "title": "[Pericentric inversions: studies in 47 cases].", "content": "The authors report 47 cases of pericentric inversion. Eleven of them involve the chromosomes No. 2, 11 and 9. It appears that the risk of malformations and/or encephalopathy is obviously increased either by \"position effect\", aneusomie de recombinaison\" or \"interchromosomal effect\". Prenatal diagnosis is therefore indicated. Thirty six cases involve the secondary constriction of chromosome No. 9. In such cases the risk is not enough increased to justify the prenatal diagnosis.", "contents": "[Pericentric inversions: studies in 47 cases]. The authors report 47 cases of pericentric inversion. Eleven of them involve the chromosomes No. 2, 11 and 9. It appears that the risk of malformations and/or encephalopathy is obviously increased either by \"position effect\", aneusomie de recombinaison\" or \"interchromosomal effect\". Prenatal diagnosis is therefore indicated. Thirty six cases involve the secondary constriction of chromosome No. 9. In such cases the risk is not enough increased to justify the prenatal diagnosis."} {"id": "PMID:161593", "title": "Heat-sensitive lambda repressors retain partial activity during bacteriophage induction.", "content": "At 43 degrees C, lambda cIts prophages are \"induced\" and enter the lytic cycle. Lac- lysogens containing heat-inducible lambda N- prophages were superinfected with a lambda trp/lac N+cI- phage containing a lacZ+ gene whose expression is controlled by the lambda cI product (repressor). Lysogens were then heated, and the synthesis of beta-galactosidase and release of progeny phage were measured. In lambda N- cIts2 or lambda N-cIts16 lysogens superinfected with lambda trp/lac N+, beta-galactosidase appeared earlier and was synthesized more rapidly than in superinfected lysogens containing lambda N- cIts857 prophage. Even at 45 degrees C, the cI857 repressor retained some activity. Lysogens containing other N-cIts mutant prophages producing renaturable repressors were also only partially derepressed at 43 degrees C. Partial derepression of lambda \"early\" transcription is sufficient for induction of lambda N+ prophages.", "contents": "Heat-sensitive lambda repressors retain partial activity during bacteriophage induction. At 43 degrees C, lambda cIts prophages are \"induced\" and enter the lytic cycle. Lac- lysogens containing heat-inducible lambda N- prophages were superinfected with a lambda trp/lac N+cI- phage containing a lacZ+ gene whose expression is controlled by the lambda cI product (repressor). Lysogens were then heated, and the synthesis of beta-galactosidase and release of progeny phage were measured. In lambda N- cIts2 or lambda N-cIts16 lysogens superinfected with lambda trp/lac N+, beta-galactosidase appeared earlier and was synthesized more rapidly than in superinfected lysogens containing lambda N- cIts857 prophage. Even at 45 degrees C, the cI857 repressor retained some activity. Lysogens containing other N-cIts mutant prophages producing renaturable repressors were also only partially derepressed at 43 degrees C. Partial derepression of lambda \"early\" transcription is sufficient for induction of lambda N+ prophages."} {"id": "PMID:161594", "title": "Accelerated immune complex nephritis due to mesangial overloading in spontaneous hypertensive (SHR) rats.", "content": "Immune complex nephritis induced by bovine serum albumin (BSA) and horseradish peroxidase (HRP) was superimposed upon spontaneous hypertensive rats (SHR rats) which were pretreated with polyvinyl alcohol (PVA). PVA accumulated predominantly in the mesangium, and the superimposed nephritis developed more accelerated glomerular damage with marked capillary deposition of immune complexes than control animals which were not pretreated with PVA.", "contents": "Accelerated immune complex nephritis due to mesangial overloading in spontaneous hypertensive (SHR) rats. Immune complex nephritis induced by bovine serum albumin (BSA) and horseradish peroxidase (HRP) was superimposed upon spontaneous hypertensive rats (SHR rats) which were pretreated with polyvinyl alcohol (PVA). PVA accumulated predominantly in the mesangium, and the superimposed nephritis developed more accelerated glomerular damage with marked capillary deposition of immune complexes than control animals which were not pretreated with PVA."} {"id": "PMID:161595", "title": "Changes in connective tissue components in ulcer tissue during the healing process of acetic acid ulcer in rats.", "content": "In order to elucidate the role of connective tissue components on the repair of ulcerated regions, quantitative changes in chemical components in ulcer tissue during the healing process were investigated in acetic acid-induced ulcer in rats. The ulcer index showed a peak on the 5th day after the operation, declined rapidly and maintained a slight level the 15th to the 60th days, without a complete recovery. In ulcer tissue, sialic acid and hexosamine remarkably increased in the early stages of healing, showing a peak on the 5th day. The patterns of time course of changes in both components ran almost parallel with those in the ulcer index. Uronic acid maintained slightly higher levels than normal levels the 5th to the 60th days. Hydroxyproline continued to increase with the time course from the 25th day. When acid mucopolysaccharides in ulcer tissue were isolated into various fractions, there were increases in hyaluronic acid on the 5th day, in chondroitin sulfate A and chondroitin sulfate C on the 30th day and chondroitin sulfate B on the 60th day, respectively. Significance of changes in these components in the healing process is discussed.", "contents": "Changes in connective tissue components in ulcer tissue during the healing process of acetic acid ulcer in rats. In order to elucidate the role of connective tissue components on the repair of ulcerated regions, quantitative changes in chemical components in ulcer tissue during the healing process were investigated in acetic acid-induced ulcer in rats. The ulcer index showed a peak on the 5th day after the operation, declined rapidly and maintained a slight level the 15th to the 60th days, without a complete recovery. In ulcer tissue, sialic acid and hexosamine remarkably increased in the early stages of healing, showing a peak on the 5th day. The patterns of time course of changes in both components ran almost parallel with those in the ulcer index. Uronic acid maintained slightly higher levels than normal levels the 5th to the 60th days. Hydroxyproline continued to increase with the time course from the 25th day. When acid mucopolysaccharides in ulcer tissue were isolated into various fractions, there were increases in hyaluronic acid on the 5th day, in chondroitin sulfate A and chondroitin sulfate C on the 30th day and chondroitin sulfate B on the 60th day, respectively. Significance of changes in these components in the healing process is discussed."} {"id": "PMID:161596", "title": "Studies on the mechanism of action of cetraxate [4'-(2-carboxyethyl)phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride], a new anti-ulcer agent.", "content": "To elucidate mechanisms involved in the anti-ulcer action of cetraxate, the effects of this agent on the ulcer index (UI), fibrinolytic activity (FA) and contents of several connective tissue components in ulcer tissue were examined using aspirin- and acetic acid ulcers in rats. In aspirin ulcer, cetraxate (100 and 300 mg/kg p.o.), like tranexamic acid (500 mg/kg p.o.), epsilon-aminocaproic acid (500 mg/kg p.o.) and gefarnate (200 mg/kg p.o.), inhibited both the UI and FA. However, aluminum sucrose sulfate (1000 mg/kg p.o.) was effective only against the UI and L-glutamine (500 mg/kg p.o.) failed to inhibit both parameters. In acetic acid ulcer, following oral, daily X either 5 or 8 administrations, cetraxate (200 and 300 mg/kg), gefarnate (200 mg/kg), aluminum sucrose sulfate (1000 mg/kg) and L-glutamine (500 mg/kg) were effective on both the UI and FA. Tranexamic acid (500 mg/kg) and epsilon-aminocaproic acid (500 mg/kg) were ineffective on the UI, although both agents inhibited FA. In acetic acid ulcer, cetraxate induced increases in hexosamine and uronic acid, that is, acid mucopolysaccharides (AMPS), especially chondroitin sulfate A and -C, whereas L-glutamine and aluminum sucrose sulfate resulted in increases in hexosamine and sialic acid, that is, glycoproteins. From these results, cetraxate may mainly accelerate the ulcer healing by increasing AMPS in ulcer tissue. Moreover, the local anti-FA property of this agent may be also beneficial in treating bleeding ulcers.", "contents": "Studies on the mechanism of action of cetraxate [4'-(2-carboxyethyl)phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride], a new anti-ulcer agent. To elucidate mechanisms involved in the anti-ulcer action of cetraxate, the effects of this agent on the ulcer index (UI), fibrinolytic activity (FA) and contents of several connective tissue components in ulcer tissue were examined using aspirin- and acetic acid ulcers in rats. In aspirin ulcer, cetraxate (100 and 300 mg/kg p.o.), like tranexamic acid (500 mg/kg p.o.), epsilon-aminocaproic acid (500 mg/kg p.o.) and gefarnate (200 mg/kg p.o.), inhibited both the UI and FA. However, aluminum sucrose sulfate (1000 mg/kg p.o.) was effective only against the UI and L-glutamine (500 mg/kg p.o.) failed to inhibit both parameters. In acetic acid ulcer, following oral, daily X either 5 or 8 administrations, cetraxate (200 and 300 mg/kg), gefarnate (200 mg/kg), aluminum sucrose sulfate (1000 mg/kg) and L-glutamine (500 mg/kg) were effective on both the UI and FA. Tranexamic acid (500 mg/kg) and epsilon-aminocaproic acid (500 mg/kg) were ineffective on the UI, although both agents inhibited FA. In acetic acid ulcer, cetraxate induced increases in hexosamine and uronic acid, that is, acid mucopolysaccharides (AMPS), especially chondroitin sulfate A and -C, whereas L-glutamine and aluminum sucrose sulfate resulted in increases in hexosamine and sialic acid, that is, glycoproteins. From these results, cetraxate may mainly accelerate the ulcer healing by increasing AMPS in ulcer tissue. Moreover, the local anti-FA property of this agent may be also beneficial in treating bleeding ulcers."} {"id": "PMID:161621", "title": "[Hansch analysis of the inhibitory action of 3- and 4-substituted benzamidines on thrombin, plasmin and trypsin (author's transl)].", "content": "Using Hansch formalism, the suthors studied quantitatively the relationship between the structure and the inhibitory action of 3- and 4-substituted amidinophenyl derivatives on thrombin, plasmin and trypsin. It was found that the inhibitory action on all three enzymes depends in the same way from the hydrophobic and electronic properties of the substituents and from an additional term in case of substituents with X-CO-Y structure. The predictive value of the equations is satisfactory.", "contents": "[Hansch analysis of the inhibitory action of 3- and 4-substituted benzamidines on thrombin, plasmin and trypsin (author's transl)]. Using Hansch formalism, the suthors studied quantitatively the relationship between the structure and the inhibitory action of 3- and 4-substituted amidinophenyl derivatives on thrombin, plasmin and trypsin. It was found that the inhibitory action on all three enzymes depends in the same way from the hydrophobic and electronic properties of the substituents and from an additional term in case of substituents with X-CO-Y structure. The predictive value of the equations is satisfactory."} {"id": "PMID:161622", "title": "[Free-Wilson analysis of the inhibitory effect of 4-substituted benzamidines on thrombin, plasmin and trypsin (author's transl)].", "content": "Using the Fujita-Ban model, the authors studied the quantitative structure-inhibitory activity relationships of a series of 4-amidinophenyl compounds with regard to thrombin, plasmin and trypsin. A satisfactory specification of the inhibitory activities was obtained from activity increments of molecular segments.", "contents": "[Free-Wilson analysis of the inhibitory effect of 4-substituted benzamidines on thrombin, plasmin and trypsin (author's transl)]. Using the Fujita-Ban model, the authors studied the quantitative structure-inhibitory activity relationships of a series of 4-amidinophenyl compounds with regard to thrombin, plasmin and trypsin. A satisfactory specification of the inhibitory activities was obtained from activity increments of molecular segments."} {"id": "PMID:161623", "title": "The mechanism of inhibition on the endogenous respiration of Ehrlich ascites tumor cells by the cyanine dye diS-C3-(5).", "content": "The cyanine dye 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide [diS-C3(5)] was found to be a potent inhibitor of endogenous respiration of Ehrlich ascites tumor cells. This effect is believed to involve both rotenone and uncoupler type actions of the dye on the electron transport system of the mitochondria.", "contents": "The mechanism of inhibition on the endogenous respiration of Ehrlich ascites tumor cells by the cyanine dye diS-C3-(5). The cyanine dye 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide [diS-C3(5)] was found to be a potent inhibitor of endogenous respiration of Ehrlich ascites tumor cells. This effect is believed to involve both rotenone and uncoupler type actions of the dye on the electron transport system of the mitochondria."} {"id": "PMID:161634", "title": "[The possibility of walking in the paralysed of the lower limbs (author's transl)].", "content": "The authors have studied the possibility of walking after rehabilitation and bracing in the paralysed of the lower limbs, it is variable with aetiological factors and age of patients. In children, walking after bracing is almost always indicated-it should be discussed case after case in adults. The authors analyse the role of different types of braces such as pneumatic braces and orthoptic systems using electrical stimulation. Some views on the future are exposed.", "contents": "[The possibility of walking in the paralysed of the lower limbs (author's transl)]. The authors have studied the possibility of walking after rehabilitation and bracing in the paralysed of the lower limbs, it is variable with aetiological factors and age of patients. In children, walking after bracing is almost always indicated-it should be discussed case after case in adults. The authors analyse the role of different types of braces such as pneumatic braces and orthoptic systems using electrical stimulation. Some views on the future are exposed."} {"id": "PMID:161635", "title": "[The influence of direct electric current on bone formation (author's transl)].", "content": "The authors have studied the effects of a 20 microampere current applied to bone in rabbits and dogs. The results have been analysed according to the age of animal, whether mature or immature, and the nature of the electrode (whether steel or platinum). They found no different in the osteogenesis produced in the medullary canal which was constant. The authors further studied the effects of currents on osteotomies of the radius in dogs which generally led to non-union in the absence of electrical currents. They failed to demonstrate any stimulation of bone repair by the current. They conclude that bone formation in the medullary canal of intact bones and the repair of fractures are two different processes.", "contents": "[The influence of direct electric current on bone formation (author's transl)]. The authors have studied the effects of a 20 microampere current applied to bone in rabbits and dogs. The results have been analysed according to the age of animal, whether mature or immature, and the nature of the electrode (whether steel or platinum). They found no different in the osteogenesis produced in the medullary canal which was constant. The authors further studied the effects of currents on osteotomies of the radius in dogs which generally led to non-union in the absence of electrical currents. They failed to demonstrate any stimulation of bone repair by the current. They conclude that bone formation in the medullary canal of intact bones and the repair of fractures are two different processes."} {"id": "PMID:161636", "title": "[A study of the potential corrosion of the madreporic prostheses compared with plane surface prostheses (author's transl)].", "content": "The authors have studied several methods of obtaining self-locking of hip prostheses without cement. They have selected a particular type of prosthesis with a \"madreporic\" surface and have studied the potential danger or corrosion in such types of prosthesis as compared with prostheses with a plane surface. They have demonstrated that, in madreporic types, the surface of the prosthesis is multiplied less than four times and that this is not dangerous provided that the metal alloy is of good quality. The methods of calculation of the surface area are described as well as experiments for testing for corrosion. These methods can be applied to other types of prosthesis.", "contents": "[A study of the potential corrosion of the madreporic prostheses compared with plane surface prostheses (author's transl)]. The authors have studied several methods of obtaining self-locking of hip prostheses without cement. They have selected a particular type of prosthesis with a \"madreporic\" surface and have studied the potential danger or corrosion in such types of prosthesis as compared with prostheses with a plane surface. They have demonstrated that, in madreporic types, the surface of the prosthesis is multiplied less than four times and that this is not dangerous provided that the metal alloy is of good quality. The methods of calculation of the surface area are described as well as experiments for testing for corrosion. These methods can be applied to other types of prosthesis."} {"id": "PMID:161637", "title": "[Is treatment of C.D.H. by progressive reduction by traction still advisable? (author's transl)].", "content": "The authors analyse the results that they have obtained in the treatment of C.D.H. either by conservative or surgical methods. The prevention of osteochondritis remains the main worry. However traction leads to long-lasting immobilization and sometimes it is not sufficient. The authors think that osteochondritis may be related to hyper-pressure on the femoral head or to lesions of the vascular pedicle and that in some cases shortening of the femur or tenotomies may allow a decrease of the plaster cast period. The indications on capculotomy, rotation osteotomy, salter osteotomy are discussed. It is concluded that the periods of traction and plaster cast immobilization should be lessened as much as possible.", "contents": "[Is treatment of C.D.H. by progressive reduction by traction still advisable? (author's transl)]. The authors analyse the results that they have obtained in the treatment of C.D.H. either by conservative or surgical methods. The prevention of osteochondritis remains the main worry. However traction leads to long-lasting immobilization and sometimes it is not sufficient. The authors think that osteochondritis may be related to hyper-pressure on the femoral head or to lesions of the vascular pedicle and that in some cases shortening of the femur or tenotomies may allow a decrease of the plaster cast period. The indications on capculotomy, rotation osteotomy, salter osteotomy are discussed. It is concluded that the periods of traction and plaster cast immobilization should be lessened as much as possible."} {"id": "PMID:161638", "title": "[Treatment of fractures of the femoral neck by primary femoral prosthesis (author's transl)].", "content": "The authors have reviewed 230 case of fractures of the femoral neck treated by primary femoral prosthesis. The mortality was 12,6 p. 100 during the first three post operative months, and 16,5 p. 100 after three additional months. The infection rate was 13,9 p. 100, 4,7 p. 100 of the cases being severely infected. The postero lateral approach was more favourable than the antero-lateral approach. Late results were studied on 142 cases. The average follow-up was 4 years. The clinical results were closely dependent on the radiological appearance. When the prosthesis progressively penetrated into the femoral medullary canal incapacitating pain was always present. It is concluded that the use of cement may improve the results in a number of cases.", "contents": "[Treatment of fractures of the femoral neck by primary femoral prosthesis (author's transl)]. The authors have reviewed 230 case of fractures of the femoral neck treated by primary femoral prosthesis. The mortality was 12,6 p. 100 during the first three post operative months, and 16,5 p. 100 after three additional months. The infection rate was 13,9 p. 100, 4,7 p. 100 of the cases being severely infected. The postero lateral approach was more favourable than the antero-lateral approach. Late results were studied on 142 cases. The average follow-up was 4 years. The clinical results were closely dependent on the radiological appearance. When the prosthesis progressively penetrated into the femoral medullary canal incapacitating pain was always present. It is concluded that the use of cement may improve the results in a number of cases."} {"id": "PMID:161640", "title": "[Bone metastasis simulating a chondrosarcoma (author's transl)].", "content": "The authors report three cases of bone tumours, two in the scapula and one in the pelvis, which simulated chondrosarcoma on radiological examination. After biopsy it was concluded that they were metastases secondary to carcinoma of the bladder in one case and of unknown origin in the other two.", "contents": "[Bone metastasis simulating a chondrosarcoma (author's transl)]. The authors report three cases of bone tumours, two in the scapula and one in the pelvis, which simulated chondrosarcoma on radiological examination. After biopsy it was concluded that they were metastases secondary to carcinoma of the bladder in one case and of unknown origin in the other two."} {"id": "PMID:161644", "title": "Injuries produced by shattering annealed glass.", "content": "Attention is drawn to the significant number of accidents related to plate (annealed) glass, and the relative paucity of information available on the subject. Four cases of life-threatening injuries secondary to accidents involving annealed glass are described and illustrated. It is suggested that the use of one of the types of safety glass already available should be made mandatory universally, but particularly in those locations defined as 'risk areas' by the British Standards Code of Practice (CP 152) on glazing in the construction industry.", "contents": "Injuries produced by shattering annealed glass. Attention is drawn to the significant number of accidents related to plate (annealed) glass, and the relative paucity of information available on the subject. Four cases of life-threatening injuries secondary to accidents involving annealed glass are described and illustrated. It is suggested that the use of one of the types of safety glass already available should be made mandatory universally, but particularly in those locations defined as 'risk areas' by the British Standards Code of Practice (CP 152) on glazing in the construction industry."} {"id": "PMID:161648", "title": "Interaction of acid glycosaminoglycans (mucopolysaccharides) with hydroxyapatite.", "content": "Selected acidic glycosaminoglycans (GAG) have been used as a model series to study some binding properties of hydroxyapatite. The order of binding was heparin, heparin sulfate, dermatan sulfage/chondroitin-4-sulfate/chondroitin-6-sulfate (all similar) and hyaluronic acid, indicating that the negative charge on the molecules is a major determinant in the binding process. Both calcium and saliva pretreatment led to an increase in uptake of selected GAG whereas fluoride even at 1 and 3 parts/106 levels led to a graded reduction in uptake. The clinical significance of these findings may be related to the presence of certain GAG in the dental integuments and to the interaction of a chemically defined group of compounds at a specific solid surface. Such findings may also have an application in studies on endogenous mineralization. The results are in accord with the generally held view that polyanions may interact electrostatically with calcium sites present in the crystal lattice of the hydroxyapatite.", "contents": "Interaction of acid glycosaminoglycans (mucopolysaccharides) with hydroxyapatite. Selected acidic glycosaminoglycans (GAG) have been used as a model series to study some binding properties of hydroxyapatite. The order of binding was heparin, heparin sulfate, dermatan sulfage/chondroitin-4-sulfate/chondroitin-6-sulfate (all similar) and hyaluronic acid, indicating that the negative charge on the molecules is a major determinant in the binding process. Both calcium and saliva pretreatment led to an increase in uptake of selected GAG whereas fluoride even at 1 and 3 parts/106 levels led to a graded reduction in uptake. The clinical significance of these findings may be related to the presence of certain GAG in the dental integuments and to the interaction of a chemically defined group of compounds at a specific solid surface. Such findings may also have an application in studies on endogenous mineralization. The results are in accord with the generally held view that polyanions may interact electrostatically with calcium sites present in the crystal lattice of the hydroxyapatite."} {"id": "PMID:161649", "title": "The effect of zolimidine, imidazopyridine-derivate, on the duodenal ulcer healing.", "content": "Zolimidine, a derivate of imidazopyridine, has a gastroprotective effect. Encouraged by the good results with zolimidine therapy in the literature we initiated a clinical study of zolimidine in duodenal ulcer healing.", "contents": "The effect of zolimidine, imidazopyridine-derivate, on the duodenal ulcer healing. Zolimidine, a derivate of imidazopyridine, has a gastroprotective effect. Encouraged by the good results with zolimidine therapy in the literature we initiated a clinical study of zolimidine in duodenal ulcer healing."} {"id": "PMID:161650", "title": "Dissociation of the humoral and cell-mediated responses to alloantigens in mice by sublethal whole-body irradiation.", "content": "Spleen cells from mice exposed to 500 rad sublethal whole-body irradiation before immunization with 100 x 10(6) allogeneic spleen cells exhibited an enhanced cytolytic T-lymphocyte (CTL) activity. In contrast, this treatment completely abrogated the humoral alloantibody response, as measured by complement-mediated lysis. In addition to the observed dissociation between primary humoral and cell-mediated responses, the character of the in vitro secondary CTL response of spleen cells obtained from mice sublethally irradiated before alloimmunization was also modified. Although these spleen cells were perfectly capable of mounting a secondary response upon restimulation in vitro with intact allogeneic spleen cells, they were no longer capable of responding to subcellular alloantigen preparations. These results suggest that the cellular requirements for the induction of secondary CTL responses in vitro depend upon the nature of the antigen used for restimulation.", "contents": "Dissociation of the humoral and cell-mediated responses to alloantigens in mice by sublethal whole-body irradiation. Spleen cells from mice exposed to 500 rad sublethal whole-body irradiation before immunization with 100 x 10(6) allogeneic spleen cells exhibited an enhanced cytolytic T-lymphocyte (CTL) activity. In contrast, this treatment completely abrogated the humoral alloantibody response, as measured by complement-mediated lysis. In addition to the observed dissociation between primary humoral and cell-mediated responses, the character of the in vitro secondary CTL response of spleen cells obtained from mice sublethally irradiated before alloimmunization was also modified. Although these spleen cells were perfectly capable of mounting a secondary response upon restimulation in vitro with intact allogeneic spleen cells, they were no longer capable of responding to subcellular alloantigen preparations. These results suggest that the cellular requirements for the induction of secondary CTL responses in vitro depend upon the nature of the antigen used for restimulation."} {"id": "PMID:161651", "title": "Induction of suppressor activity on B-cell differentiation in human T-cell subset without fc(IgG) receptors by levamisole administration.", "content": "A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor-bearing T cells (T gamma cells) increased for 5 days after levamisole intake, but total E rosette-forming cells showed no significant alterations. The generation of immunoglobulin-producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)-stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T-cell activity on B-cell differentiation, which was induced by levamisole intake, was evaluated by co-culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose-dependent suppression on B-cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T-cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in T gamma cells.", "contents": "Induction of suppressor activity on B-cell differentiation in human T-cell subset without fc(IgG) receptors by levamisole administration. A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor-bearing T cells (T gamma cells) increased for 5 days after levamisole intake, but total E rosette-forming cells showed no significant alterations. The generation of immunoglobulin-producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)-stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T-cell activity on B-cell differentiation, which was induced by levamisole intake, was evaluated by co-culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose-dependent suppression on B-cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T-cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in T gamma cells."} {"id": "PMID:161652", "title": "Aortic valve replacement. A randomized study comparing the Bj\u00f6rk-Shiley and Lillehei-Kaster disc valves. Late haemodynamics related to clinical results.", "content": "In this study, 78 randomized patients with either Bj\u00f6rk-Shiley (B-S) or Lillehei-Kaster (L-K) aortic disc valve prostheses were re-admitted for clinical and haemodynamic evaluation. The patients were selected that those with narrow aortic roots were over-represented. Cine-aortography was carried out in 75 patients and left ventricular catheterisation via the transseptal approach was performed in 42. The clinical improvement was striking, although the number of patients still incapacitated was relatively large in patients with the small L-K valves (Nos. 14 & 16). Peak-to-peak and mean systolic pressure differences across the valves were significantly lower in the B-S than in the L-K valves, particularly when the small valve sizes were compared. Left ventricular end-diastolic pressure (LVEDP), which was elevated in most patients before operation, decreased significantly to normal levels in the B-S group. In the L-K group, LVEDP did not decrease significantly and was on the average still above the normal level after operation, probably due to the relatively large pressure gradients. The study indicates that the L-K valves Nos. 14 & 16 in particular represents a resistance to flow that is too large to be acceptable in clinical practice.", "contents": "Aortic valve replacement. A randomized study comparing the Bj\u00f6rk-Shiley and Lillehei-Kaster disc valves. Late haemodynamics related to clinical results. In this study, 78 randomized patients with either Bj\u00f6rk-Shiley (B-S) or Lillehei-Kaster (L-K) aortic disc valve prostheses were re-admitted for clinical and haemodynamic evaluation. The patients were selected that those with narrow aortic roots were over-represented. Cine-aortography was carried out in 75 patients and left ventricular catheterisation via the transseptal approach was performed in 42. The clinical improvement was striking, although the number of patients still incapacitated was relatively large in patients with the small L-K valves (Nos. 14 & 16). Peak-to-peak and mean systolic pressure differences across the valves were significantly lower in the B-S than in the L-K valves, particularly when the small valve sizes were compared. Left ventricular end-diastolic pressure (LVEDP), which was elevated in most patients before operation, decreased significantly to normal levels in the B-S group. In the L-K group, LVEDP did not decrease significantly and was on the average still above the normal level after operation, probably due to the relatively large pressure gradients. The study indicates that the L-K valves Nos. 14 & 16 in particular represents a resistance to flow that is too large to be acceptable in clinical practice."} {"id": "PMID:161667", "title": "Comparison of the new miniature Wright peak flow meter with the standard Wright peak flow meter.", "content": "Preproduction and current models of the miniature Wright peak flow meter have been compared with the standard Wright peak flow meter on normal and abnormal subjects. Early problems in production appear to have been overcome, and the current model agrees to within 3% with the standard peak flow meter, which is as close as the agreement between two standard instruments. The new mini-meter may be enclosed in a case, making direct comparisons with other instruments possible.", "contents": "Comparison of the new miniature Wright peak flow meter with the standard Wright peak flow meter. Preproduction and current models of the miniature Wright peak flow meter have been compared with the standard Wright peak flow meter on normal and abnormal subjects. Early problems in production appear to have been overcome, and the current model agrees to within 3% with the standard peak flow meter, which is as close as the agreement between two standard instruments. The new mini-meter may be enclosed in a case, making direct comparisons with other instruments possible."} {"id": "PMID:161668", "title": "Fibrin suspension as a substrate fop plasmin: determination and kinetics.", "content": "Fibrin polymers formed from fibrinogen with thrombin in the presence of EDTA were suspended in a medium containing glucose, arabic gum and imidazole-HCl buffer and were sonicated at 20 kHz for 20 min to make a suspension containing fibrin particles of small size. The fibrin suspension was used as a substrate of plasmin for determining the enzymic activity of plasmin and plasminogen activated with urokinase. The kinetic study on the reaction of the fibrin particles with plasmin in the presence and the absence of fibrinogen revealed that Km value of fibrin for plasmin is 4.2 x 10(-7) M and the Ki value of fibrinogen is 1.2 x 10(-5) M.", "contents": "Fibrin suspension as a substrate fop plasmin: determination and kinetics. Fibrin polymers formed from fibrinogen with thrombin in the presence of EDTA were suspended in a medium containing glucose, arabic gum and imidazole-HCl buffer and were sonicated at 20 kHz for 20 min to make a suspension containing fibrin particles of small size. The fibrin suspension was used as a substrate of plasmin for determining the enzymic activity of plasmin and plasminogen activated with urokinase. The kinetic study on the reaction of the fibrin particles with plasmin in the presence and the absence of fibrinogen revealed that Km value of fibrin for plasmin is 4.2 x 10(-7) M and the Ki value of fibrinogen is 1.2 x 10(-5) M."} {"id": "PMID:161669", "title": "The interaction between heparin and plasmin on amidolysis.", "content": "The effect of the interaction between heparin and plasmin not only on fibrinolytic, caseinolytic and esterolytic activities but also on amidolytic activity, since plasmin has amidolytic or amidase activity, was investigated. Following were the results obtained from these investigations: 1. Heparin enhanced amidolytic activity of a fixed level of plasmin which was prepared by activating plasminogen with urokinase within the range from 2 to 64 units/ml of the final concentration of heparin. 2. Heparin also enhanced amidolytic activity of a fixed level of plasmin which was prepared by converting plasminogen with insolubilized urokinase. 3. Heparin did not enhance or inhibit fibrinolytic, caseinolytic and esterolytic activities of a fixed level of plasmin which was prepared by activating plasminogen with urokinase, in the fibrinolytic activity within the range from 0.032 to 125 units/ml, in the caseinolytic activity within the range from 0.0125 to 100 units/ml, and in the esterolytic activity within the range from 0.016 to 128 units/ml, of the final concentration of heparin respectively.", "contents": "The interaction between heparin and plasmin on amidolysis. The effect of the interaction between heparin and plasmin not only on fibrinolytic, caseinolytic and esterolytic activities but also on amidolytic activity, since plasmin has amidolytic or amidase activity, was investigated. Following were the results obtained from these investigations: 1. Heparin enhanced amidolytic activity of a fixed level of plasmin which was prepared by activating plasminogen with urokinase within the range from 2 to 64 units/ml of the final concentration of heparin. 2. Heparin also enhanced amidolytic activity of a fixed level of plasmin which was prepared by converting plasminogen with insolubilized urokinase. 3. Heparin did not enhance or inhibit fibrinolytic, caseinolytic and esterolytic activities of a fixed level of plasmin which was prepared by activating plasminogen with urokinase, in the fibrinolytic activity within the range from 0.032 to 125 units/ml, in the caseinolytic activity within the range from 0.0125 to 100 units/ml, and in the esterolytic activity within the range from 0.016 to 128 units/ml, of the final concentration of heparin respectively."} {"id": "PMID:161670", "title": "Lipomatous hypertrophy of interatrial septum presenting as recurring pericardial effusion and mistaken for constrictive pericarditis.", "content": "A case of interatrial septal lipoma, presenting as recurrent pericardial effusion with signs of constrictive pericarditis, was described. The tumor was removed successfully. The case demonstrated that the difficulties in the differential diagnosis between right atrial tumor and any other cardiac disease still exist. Because of its extreme rarity, the interatrial septal lipoma is rarely considered in the differential diagnosis.", "contents": "Lipomatous hypertrophy of interatrial septum presenting as recurring pericardial effusion and mistaken for constrictive pericarditis. A case of interatrial septal lipoma, presenting as recurrent pericardial effusion with signs of constrictive pericarditis, was described. The tumor was removed successfully. The case demonstrated that the difficulties in the differential diagnosis between right atrial tumor and any other cardiac disease still exist. Because of its extreme rarity, the interatrial septal lipoma is rarely considered in the differential diagnosis."} {"id": "PMID:161677", "title": "Linkage relationship of C2 deficiency, HLA and glyoxalase I loci.", "content": "Immunogenetic analysis of a homozygous C2-deficient individual and family members demonstrated linkage of HLA-A25, B18 and C2o. HLA-D typing showed that 5 members typed with homozygous Dw2 typing cells from an individual with C2 deficiency but not with Dw2 typing cells from 2 individuals with normal C2. The homozygous C2-deficient propositus and brother were HLA-A and B homozygous but heterozygous at the HLA-D and glyoxalase I loci. Therefore, in this family, the C2o gene is linked with two distinct haplotypes: HLA-A25, B18, Dw2, GLO1 and HLA-A25, B18, D unknown, GL02. These results could be explained by an ancestral recombinant event, which occurred between the C2o locus and HLA-D locus in which C2o segregated with HLA-B. This would suggest that the locus for the C2o gene maps between HLA-B and HLA-D on the sixth chromosome.", "contents": "Linkage relationship of C2 deficiency, HLA and glyoxalase I loci. Immunogenetic analysis of a homozygous C2-deficient individual and family members demonstrated linkage of HLA-A25, B18 and C2o. HLA-D typing showed that 5 members typed with homozygous Dw2 typing cells from an individual with C2 deficiency but not with Dw2 typing cells from 2 individuals with normal C2. The homozygous C2-deficient propositus and brother were HLA-A and B homozygous but heterozygous at the HLA-D and glyoxalase I loci. Therefore, in this family, the C2o gene is linked with two distinct haplotypes: HLA-A25, B18, Dw2, GLO1 and HLA-A25, B18, D unknown, GL02. These results could be explained by an ancestral recombinant event, which occurred between the C2o locus and HLA-D locus in which C2o segregated with HLA-B. This would suggest that the locus for the C2o gene maps between HLA-B and HLA-D on the sixth chromosome."} {"id": "PMID:161679", "title": "[Effect of the detergent Metaupon on replication of various phages].", "content": "As several other surfactants do, the detergent Metaupon acts on the multiplication of bacteriophages. We investigated the influence of Metaupon on the phages phi and lambda, the cyanophage LPP-1, and the RNA-phages f 2, M 12, and Q beta by means of the agar diffusion test, pour plate test, adsorption test, and one-step growth test. The action of Metaupon on the free phages was also tested. Metaupon inhibits the formation of plaques by the phages with exception of lambda. With the phages f 2 and M 12 the substance increases the amount of plaques depending on concentration. The main mode of action of Metaupon was found to be the inhibition of the adsorption of the phages to the host cells. Only in the case of phi 105 free phages were inactivated.", "contents": "[Effect of the detergent Metaupon on replication of various phages]. As several other surfactants do, the detergent Metaupon acts on the multiplication of bacteriophages. We investigated the influence of Metaupon on the phages phi and lambda, the cyanophage LPP-1, and the RNA-phages f 2, M 12, and Q beta by means of the agar diffusion test, pour plate test, adsorption test, and one-step growth test. The action of Metaupon on the free phages was also tested. Metaupon inhibits the formation of plaques by the phages with exception of lambda. With the phages f 2 and M 12 the substance increases the amount of plaques depending on concentration. The main mode of action of Metaupon was found to be the inhibition of the adsorption of the phages to the host cells. Only in the case of phi 105 free phages were inactivated."} {"id": "PMID:161681", "title": "[Laparoscopy in chronic gallbladder diseases].", "content": "The laparoscopy is the only riskless possibility of directly inspecting the gall-bladder, to ascertain the diagnosis of a chronic cholecystitis, further to consider the indications to internal or surgical measures. For the judgment the form of the gall-bladder, the behaviour of its wall with different colouring, oedema and furthermore its behaviour to neighbouring organs are of decisive evidence. In a disease of the bile-ducts the laparoscopy allows to prove or to exclude a participation of the liver. For the judgment of the activity of a disease of the gall-bladder should, however, always be used clinical and radiological findings, the microbiological investigation of the A-, B-, and C-bile and the testing of the reflex of the gall-bladder. This is necessary with regard to the therapy.", "contents": "[Laparoscopy in chronic gallbladder diseases]. The laparoscopy is the only riskless possibility of directly inspecting the gall-bladder, to ascertain the diagnosis of a chronic cholecystitis, further to consider the indications to internal or surgical measures. For the judgment the form of the gall-bladder, the behaviour of its wall with different colouring, oedema and furthermore its behaviour to neighbouring organs are of decisive evidence. In a disease of the bile-ducts the laparoscopy allows to prove or to exclude a participation of the liver. For the judgment of the activity of a disease of the gall-bladder should, however, always be used clinical and radiological findings, the microbiological investigation of the A-, B-, and C-bile and the testing of the reflex of the gall-bladder. This is necessary with regard to the therapy."} {"id": "PMID:161683", "title": "[Partial atrial standstill with sick-sinus-syndrome accompanying a case of cardiomyopathy (author's transl)].", "content": "In a patient with cardiomyopathy of unknown etiology and clinical manifestation of SSS (sick-sinus syndrome) the electro-physiological examination and the registration of pressure curves indicated a mechanical and electrical partial standstill of both atria. Some electro-physiologically interesting phenomena found during the His-catheterization are described.", "contents": "[Partial atrial standstill with sick-sinus-syndrome accompanying a case of cardiomyopathy (author's transl)]. In a patient with cardiomyopathy of unknown etiology and clinical manifestation of SSS (sick-sinus syndrome) the electro-physiological examination and the registration of pressure curves indicated a mechanical and electrical partial standstill of both atria. Some electro-physiologically interesting phenomena found during the His-catheterization are described."} {"id": "PMID:161684", "title": "[Coronary vessel anomaly: fistula between the right coronary artery and the left ventricle clinically presenting as aortic valve insufficiency (author's transl)].", "content": "Under more than 200 cases of coronary vessel anomalies only 33 are fistulas from the right or left coronary artery into the left ventricle. The case presented here of a fistula from the right coronary artery into the left ventricle featured the clinical picture of an aortic valve insufficiency. The histologic findings support the theory that these fistulas are embryological anomalies: transient communications between the ventricular trabeculas and the coronary vessels may be lined with endothelium and become then persisting as fistulas.", "contents": "[Coronary vessel anomaly: fistula between the right coronary artery and the left ventricle clinically presenting as aortic valve insufficiency (author's transl)]. Under more than 200 cases of coronary vessel anomalies only 33 are fistulas from the right or left coronary artery into the left ventricle. The case presented here of a fistula from the right coronary artery into the left ventricle featured the clinical picture of an aortic valve insufficiency. The histologic findings support the theory that these fistulas are embryological anomalies: transient communications between the ventricular trabeculas and the coronary vessels may be lined with endothelium and become then persisting as fistulas."} {"id": "PMID:161686", "title": "Relation of occupational stress to the age at onset of Huntington's disease.", "content": "Two hypotheses were tested to determine whether occupational stress was related to the age at onset of Huntington's disease. Using case material drawn from four kindreds in southern Norway, occupations of affected persons were graded into three categories according to their degree of physical stress. Adjusting for the effects of related factors, grade of stress was found to be a significant contributor to the variation in onset age. Minor and severe stress were associated with earlier onset ages than moderate stress; the difference between minor and moderate grades was 9 years. The results are interpreted as conforming to the psychosocial concept of Levi, whereby both under- and overstimulation of sensory functions are more stressful and more potent precipitants of illness than intermediate levels of stimulation.", "contents": "Relation of occupational stress to the age at onset of Huntington's disease. Two hypotheses were tested to determine whether occupational stress was related to the age at onset of Huntington's disease. Using case material drawn from four kindreds in southern Norway, occupations of affected persons were graded into three categories according to their degree of physical stress. Adjusting for the effects of related factors, grade of stress was found to be a significant contributor to the variation in onset age. Minor and severe stress were associated with earlier onset ages than moderate stress; the difference between minor and moderate grades was 9 years. The results are interpreted as conforming to the psychosocial concept of Levi, whereby both under- and overstimulation of sensory functions are more stressful and more potent precipitants of illness than intermediate levels of stimulation."} {"id": "PMID:161687", "title": "Changes in the contractile material of human skeletal muscle following tendinous injury.", "content": "The most marked changes in the human muscle following tendinous injury can be observed in the contractile components. There is a widening of the Z-membrane, dispersion of the sarcomers, a break in their continuity, and detached bundles of myofibrils are found in the sarcoplasm. A change occurs also in the proportion of different fibre types of the muscles, in the muscle with tendinous injury a predominance of type II fibre becoming apparent. Among the proteins of myofibrils a product of disintegration of a molecular weight of 31 000 can be consequently demonstrated, and in some muscles products of disintegration with a molecular weight between 90 000 and 58,000 arise.", "contents": "Changes in the contractile material of human skeletal muscle following tendinous injury. The most marked changes in the human muscle following tendinous injury can be observed in the contractile components. There is a widening of the Z-membrane, dispersion of the sarcomers, a break in their continuity, and detached bundles of myofibrils are found in the sarcoplasm. A change occurs also in the proportion of different fibre types of the muscles, in the muscle with tendinous injury a predominance of type II fibre becoming apparent. Among the proteins of myofibrils a product of disintegration of a molecular weight of 31 000 can be consequently demonstrated, and in some muscles products of disintegration with a molecular weight between 90 000 and 58,000 arise."} {"id": "PMID:161688", "title": "Fibre types in human abdominal muscles.", "content": "Histochemical muscle fibre composition was studied in biopsied from the four different muscles of the abdominal wall (rectus abdominis, RA, obliquus externus, OE, obliquus internus, OI, and transversus abdominis, Tr) in 13 normal human subjects (9 females and 4 males, age 24-55 years) undergoing gall-bladder surgery. Muscle fibres were classified as Type I, IIA, IIB or IIC on the basis of their myofibrillar ATPases' pH lability. There were large inter-individual variations in fibre composition, whereas, in general, the differences between the different muscles were minor or non-existent. Mean fibre distribution ranges were 55-58% I, 15-23% 22A, 21-28% IIB, and 0-1% II C fibres. The least fibre diameters were similar for all types and muscles (range of means 50-54 micrometer) except for Tr in which the Type II fibres were smaller (mean 45 micrometer). There was a high correlation in the size of Type I vs. II fibres and Type IIA vs. IIB fibres in all layers. The oxidative potential (NADH-diaphorase staining intensity) appeared high in Type I fibres and low in Type II fibres, irrespective of subgroups. Thus, based on histochemical fibre composition, the different abdominal muscles appear to have a similar functional capacity. However, functional differences between individuals were indicated by the large inter-individual variation in muscle fibre distribution.", "contents": "Fibre types in human abdominal muscles. Histochemical muscle fibre composition was studied in biopsied from the four different muscles of the abdominal wall (rectus abdominis, RA, obliquus externus, OE, obliquus internus, OI, and transversus abdominis, Tr) in 13 normal human subjects (9 females and 4 males, age 24-55 years) undergoing gall-bladder surgery. Muscle fibres were classified as Type I, IIA, IIB or IIC on the basis of their myofibrillar ATPases' pH lability. There were large inter-individual variations in fibre composition, whereas, in general, the differences between the different muscles were minor or non-existent. Mean fibre distribution ranges were 55-58% I, 15-23% 22A, 21-28% IIB, and 0-1% II C fibres. The least fibre diameters were similar for all types and muscles (range of means 50-54 micrometer) except for Tr in which the Type II fibres were smaller (mean 45 micrometer). There was a high correlation in the size of Type I vs. II fibres and Type IIA vs. IIB fibres in all layers. The oxidative potential (NADH-diaphorase staining intensity) appeared high in Type I fibres and low in Type II fibres, irrespective of subgroups. Thus, based on histochemical fibre composition, the different abdominal muscles appear to have a similar functional capacity. However, functional differences between individuals were indicated by the large inter-individual variation in muscle fibre distribution."} {"id": "PMID:161689", "title": "Functional implications of the two-headed structure of myosin.", "content": "This review summarizes the results obtained by biochemical and physiological studies on the functional implications of the two-headed structure of the myosin molecule. Our nonidentical two-head hypothesis of myosin is supported by biochemical studies on myosin ATPase. The reaction mechanism of the Mg2+-ATPase reaction catalyzed by one head of the myosin molecule is shown to be different from that catalyzed by the other head, and the reaction intermediate, MPADP, is produced in head B but not in head A. Evidence for differences in the chemical structures of the two heads of myosin is also presented. The myosin preparation is shown to be a mixture of homodimers with respect to its g-chain composition, but every homodimer has the non-identical two heads, B and A. Furthermore, the molecular mechanism for acceleration of the Mg2+-ATPase reaction by F-actin and that for its control by Ca2+ ions and Mg2+-ATP are discussed, based on the nonidentical two-head hypothesis of the myosin molecule. It was shown that the formation and decomposition of the key intermediate, A(B)MPADP are required for tension development and shortening. One cycle of ATP hydrolysis by crossbridges synchronously initiated by a rapid stretch or a sudden release of a slow stretch, indicating that the probability of dissociation of a crossbridge by its interaction with ATP depends on its angular position. It is also demonstrated that rotation of the base of nucleoside triphosphate about the glycosyl bond is essential for formation of MPXDP from M2XTP, as well as for muscle contraction. Based on these biochemical and physiological studies on the movement of the myosin head in muscle contraction, a molecular mechanism for muscle contraction is proposed.", "contents": "Functional implications of the two-headed structure of myosin. This review summarizes the results obtained by biochemical and physiological studies on the functional implications of the two-headed structure of the myosin molecule. Our nonidentical two-head hypothesis of myosin is supported by biochemical studies on myosin ATPase. The reaction mechanism of the Mg2+-ATPase reaction catalyzed by one head of the myosin molecule is shown to be different from that catalyzed by the other head, and the reaction intermediate, MPADP, is produced in head B but not in head A. Evidence for differences in the chemical structures of the two heads of myosin is also presented. The myosin preparation is shown to be a mixture of homodimers with respect to its g-chain composition, but every homodimer has the non-identical two heads, B and A. Furthermore, the molecular mechanism for acceleration of the Mg2+-ATPase reaction by F-actin and that for its control by Ca2+ ions and Mg2+-ATP are discussed, based on the nonidentical two-head hypothesis of the myosin molecule. It was shown that the formation and decomposition of the key intermediate, A(B)MPADP are required for tension development and shortening. One cycle of ATP hydrolysis by crossbridges synchronously initiated by a rapid stretch or a sudden release of a slow stretch, indicating that the probability of dissociation of a crossbridge by its interaction with ATP depends on its angular position. It is also demonstrated that rotation of the base of nucleoside triphosphate about the glycosyl bond is essential for formation of MPXDP from M2XTP, as well as for muscle contraction. Based on these biochemical and physiological studies on the movement of the myosin head in muscle contraction, a molecular mechanism for muscle contraction is proposed."} {"id": "PMID:161690", "title": "Dynamic cooperativity of molecular processes in active streaming, muscle contraction, and subcellular dynamics: the molecular mechanism of self-organization at the subcellular level.", "content": "Life phenomena are a kind of ordered dynamics appearing in macroscopic systems, living systems. Schr\u00f6dinger has proposed a molecular mechanism for the organization of life phenomena, i.e., 'order-from-order' mechanism where ordered dynamics are composed of molecular dynamics having order as the ordered dynamics of a watch is caused by orderly movements of its mechanical elements. However, neither evidence supporting the 'order-from-order' mechanism has been found in living systems nor the reason why molecular dynamics acquire order instead of disorder has been elucidated for more than 30 years. The latter is quite anomalous from the point of views of thermodynamics, which is based on disordered behaviors of molecules. In this paper, we verify from studies of a streaming system reconstituted from rabbit skeletal F-actin and HMM that one life phenomenon, active streaming, is caused by the 'order-from-order' mechanism. This is also the case for muscle contraction. Moreover, it is probable that this mechanism generally works at the subcellular level, not only in biological motilities but also in life phenomena at biomembranes. We also clarify that dynamic cooperativity among molecule gives rise to order in molecular dynamics. Hence, dynamic cooperativity is the key mechanism for life phenomena caused by the 'order-from-order' principle at the subcellular level. To produce dynamic cooperativity it is necessary for component molecules or elements to have three states, i.e., inactive (stable) state 0, energized or energy storing (quasi-stable) state 1, and active (unstable) state 2. Each molecule performs elementary cycle 0 yields 1 yields 2 yields 0 repeatedly by using free energy at the molecular level. In a state far from thermodynamic equilibrium dynamic cooperativity is yielded in 2 yields 0 due to a kind of triggering action of neighboring elements and breaks thermodynamic detailed balance. In addition, dynamic cooperativity gives component molecules long-range interactions which depend on the structure of organelles or molecular assemblies. Dynamic cooperativity is able to decrease entropy production and will give a high efficiency in chemo-mechanical conversions. Great progress would be achieved in the understanding of the molecular mechanisms and thermodynamic principles of energy transformations in biological systems, if molecular dynamics during transformation could be directly observed. This is not only because physical changes accompanied by specific movements of macromolecules are essentially involved but also because such molecular movements play a substantial role in energy transformation. Entirely new ideas will be needed for this purpose although high voltage electron microscopy or X-ray diffraction, for instance, is now expected as to be one of the possible tools in the future. Fortunately even at present it is possible to obtain important information on molecular dynamics from biochemical and physiological data, if analyses are properly performed...", "contents": "Dynamic cooperativity of molecular processes in active streaming, muscle contraction, and subcellular dynamics: the molecular mechanism of self-organization at the subcellular level. Life phenomena are a kind of ordered dynamics appearing in macroscopic systems, living systems. Schr\u00f6dinger has proposed a molecular mechanism for the organization of life phenomena, i.e., 'order-from-order' mechanism where ordered dynamics are composed of molecular dynamics having order as the ordered dynamics of a watch is caused by orderly movements of its mechanical elements. However, neither evidence supporting the 'order-from-order' mechanism has been found in living systems nor the reason why molecular dynamics acquire order instead of disorder has been elucidated for more than 30 years. The latter is quite anomalous from the point of views of thermodynamics, which is based on disordered behaviors of molecules. In this paper, we verify from studies of a streaming system reconstituted from rabbit skeletal F-actin and HMM that one life phenomenon, active streaming, is caused by the 'order-from-order' mechanism. This is also the case for muscle contraction. Moreover, it is probable that this mechanism generally works at the subcellular level, not only in biological motilities but also in life phenomena at biomembranes. We also clarify that dynamic cooperativity among molecule gives rise to order in molecular dynamics. Hence, dynamic cooperativity is the key mechanism for life phenomena caused by the 'order-from-order' principle at the subcellular level. To produce dynamic cooperativity it is necessary for component molecules or elements to have three states, i.e., inactive (stable) state 0, energized or energy storing (quasi-stable) state 1, and active (unstable) state 2. Each molecule performs elementary cycle 0 yields 1 yields 2 yields 0 repeatedly by using free energy at the molecular level. In a state far from thermodynamic equilibrium dynamic cooperativity is yielded in 2 yields 0 due to a kind of triggering action of neighboring elements and breaks thermodynamic detailed balance. In addition, dynamic cooperativity gives component molecules long-range interactions which depend on the structure of organelles or molecular assemblies. Dynamic cooperativity is able to decrease entropy production and will give a high efficiency in chemo-mechanical conversions. Great progress would be achieved in the understanding of the molecular mechanisms and thermodynamic principles of energy transformations in biological systems, if molecular dynamics during transformation could be directly observed. This is not only because physical changes accompanied by specific movements of macromolecules are essentially involved but also because such molecular movements play a substantial role in energy transformation. Entirely new ideas will be needed for this purpose although high voltage electron microscopy or X-ray diffraction, for instance, is now expected as to be one of the possible tools in the future. Fortunately even at present it is possible to obtain important information on molecular dynamics from biochemical and physiological data, if analyses are properly performed..."} {"id": "PMID:161691", "title": "Treatment of low back pain with acupuncture.", "content": "Twenty patients with low back pain were selected for treatment with acupuncture. Four standard acupuncture loci and a standard regime were used. The results were analyzed after a follow-up of 12 months. Initially, 16 patients responded favorably to the treatment while 4 did not respond at all. The degree of cure was not uniform. Instead they varied from complete cure in 4 to varying degrees of alleviation of pain in the rest. Recurrence or acute exacerbation of symptoms occurred in 13 of the 20 patients. Acupuncture was given to 11 of these patients and the results of treatment similated the initial course of acupuncture.", "contents": "Treatment of low back pain with acupuncture. Twenty patients with low back pain were selected for treatment with acupuncture. Four standard acupuncture loci and a standard regime were used. The results were analyzed after a follow-up of 12 months. Initially, 16 patients responded favorably to the treatment while 4 did not respond at all. The degree of cure was not uniform. Instead they varied from complete cure in 4 to varying degrees of alleviation of pain in the rest. Recurrence or acute exacerbation of symptoms occurred in 13 of the 20 patients. Acupuncture was given to 11 of these patients and the results of treatment similated the initial course of acupuncture."} {"id": "PMID:161692", "title": "Disc vascularity in Down's syndrome.", "content": "Ocular fundus photographs of 100 eyes were obtained from an institutionalized population of patients with Down's Syndrome (66 males, 34 females). The vascularity of the optic nerve head was assessed in each photograph by counting the number of arterioles, venules, and fine vessels crossing the disc margin. The results of this analysis were compared to similar data obtained from 100 ocular fundus photographs of normal patients and show that there are more large vessels crossing the disc margin in those with Down's Syndrome.", "contents": "Disc vascularity in Down's syndrome. Ocular fundus photographs of 100 eyes were obtained from an institutionalized population of patients with Down's Syndrome (66 males, 34 females). The vascularity of the optic nerve head was assessed in each photograph by counting the number of arterioles, venules, and fine vessels crossing the disc margin. The results of this analysis were compared to similar data obtained from 100 ocular fundus photographs of normal patients and show that there are more large vessels crossing the disc margin in those with Down's Syndrome."} {"id": "PMID:161694", "title": "The fibrinolysin system and its relationship to disease in the newborn.", "content": "The fibrinolysin system is incomplete in newborn infants. Lack of serum plasminogen in premature newborn has an important role in the pathophysiology of the respiratory distress syndrome since alveolar fibrin deposits cannot be eliminated. Urokinase activated human plasmin has increased the survival rate of infants with respiratory distress syndrome. Plasminogen given I.V. at birth has reduced the incidence and the severity of respiratory distress syndrome, in a randomized double-blind study of 500 premature infants. Death in the plasminogen recipient group occurred only among infants born to mothers with bleeding complications of pregnancy. Plasmin inhibitors measured with a functional assay were the highest in this group of infants, serum plasminogen was the lowest; when activator and purified human plasminogen were added to the serum, fibrinolytic activity was elicited in excess of the plasminogen added. It is suggested that plasminogen and/or plasmin inhibitors may be abnormal fetal variants in infants born to mothers with bleeding complications.", "contents": "The fibrinolysin system and its relationship to disease in the newborn. The fibrinolysin system is incomplete in newborn infants. Lack of serum plasminogen in premature newborn has an important role in the pathophysiology of the respiratory distress syndrome since alveolar fibrin deposits cannot be eliminated. Urokinase activated human plasmin has increased the survival rate of infants with respiratory distress syndrome. Plasminogen given I.V. at birth has reduced the incidence and the severity of respiratory distress syndrome, in a randomized double-blind study of 500 premature infants. Death in the plasminogen recipient group occurred only among infants born to mothers with bleeding complications of pregnancy. Plasmin inhibitors measured with a functional assay were the highest in this group of infants, serum plasminogen was the lowest; when activator and purified human plasminogen were added to the serum, fibrinolytic activity was elicited in excess of the plasminogen added. It is suggested that plasminogen and/or plasmin inhibitors may be abnormal fetal variants in infants born to mothers with bleeding complications."} {"id": "PMID:161700", "title": "Comparison of the effects of a non-steroidal anti-inflammatory agent, an immunosuppressive, a corticosteroid and an immunomodulator on various immunological and non-immunological inflammatory experimental models.", "content": "The effects of a non-steroidal anti-inflammatory agent, phenylbutazone, a corticosteroid, desonide, an immunosuppressive, cyclophosphamide and an immunomodulator, levamisole on a number of experimental inflammatory models were compared. Compounds were first tested in carrageenin-induced pleurisy as a non-immune acute inflammation, then in passive skin anaphylaxis and reversed passive Arthus oedema in the rat as models of humoral immunity. Finally the compounds were investigated in various delayed hypersensitivity tests: reaction to sheep red cells and to oxazolone in the mouse, skin reaction to purified protein derivative (P.P.D.) in the rat and guinea-pig, P.P.D. induced pleurisy in the guinea-pig.", "contents": "Comparison of the effects of a non-steroidal anti-inflammatory agent, an immunosuppressive, a corticosteroid and an immunomodulator on various immunological and non-immunological inflammatory experimental models. The effects of a non-steroidal anti-inflammatory agent, phenylbutazone, a corticosteroid, desonide, an immunosuppressive, cyclophosphamide and an immunomodulator, levamisole on a number of experimental inflammatory models were compared. Compounds were first tested in carrageenin-induced pleurisy as a non-immune acute inflammation, then in passive skin anaphylaxis and reversed passive Arthus oedema in the rat as models of humoral immunity. Finally the compounds were investigated in various delayed hypersensitivity tests: reaction to sheep red cells and to oxazolone in the mouse, skin reaction to purified protein derivative (P.P.D.) in the rat and guinea-pig, P.P.D. induced pleurisy in the guinea-pig."} {"id": "PMID:161703", "title": "Sterilization: a comparative review.", "content": "Publications relating to surgical procedures for sterilization have been reviewed, and the incidences of complications and subsequent pregnancies compared. Laparoscopic sterilization has the lowest incidence of complication, the morbidity rate being lower than that of laparotomy sterilization or hysterectomy, and the mortality rate lower than that of a single pregnancy or taking oral contraceptives for 1 year.", "contents": "Sterilization: a comparative review. Publications relating to surgical procedures for sterilization have been reviewed, and the incidences of complications and subsequent pregnancies compared. Laparoscopic sterilization has the lowest incidence of complication, the morbidity rate being lower than that of laparotomy sterilization or hysterectomy, and the mortality rate lower than that of a single pregnancy or taking oral contraceptives for 1 year."} {"id": "PMID:161704", "title": "Prenatal diagnosis of placental sulphatase deficiency.", "content": "A gas chromatographic procedure for the quantitation of neutral steroid sulphates in maternal urine and its application to a suspected case of placental sulphatase deficiency is described. Low levels of oestriol coincident with elevated 16-hydroxylated metabolites of dehydroepiandrosterone in the maternal urine are shown to occur in this particular condition, and thus provide a convenient differentiation from fetal adrenal hypoplasia before birth.", "contents": "Prenatal diagnosis of placental sulphatase deficiency. A gas chromatographic procedure for the quantitation of neutral steroid sulphates in maternal urine and its application to a suspected case of placental sulphatase deficiency is described. Low levels of oestriol coincident with elevated 16-hydroxylated metabolites of dehydroepiandrosterone in the maternal urine are shown to occur in this particular condition, and thus provide a convenient differentiation from fetal adrenal hypoplasia before birth."} {"id": "PMID:161705", "title": "A case of cornual pregnancy.", "content": "A case of cornual pregnancy was uncertain at laparoscopy, made by ultrasound, and confirmed at laparotomy.", "contents": "A case of cornual pregnancy. A case of cornual pregnancy was uncertain at laparoscopy, made by ultrasound, and confirmed at laparotomy."} {"id": "PMID:161729", "title": "[Production of urea during mixed leukocyte culture (MLC). Effect of presensitization by a skin allograft].", "content": "An increased production of urea has been demonstrated during mixed cultures between allograft donor and recipient leukocytes. This phenomenon may also be observed during primary MLC (i.e, without previous allograft) but to a lesser degree. This increased production of urea during MLC results from an increase of arginase activity in spleen cell population(s) resulting in an increased arginine transformation into urea and ornithine, as demonstrated by the release of an amount of ornithine equivalent to that of urea in the culture supernatant.", "contents": "[Production of urea during mixed leukocyte culture (MLC). Effect of presensitization by a skin allograft]. An increased production of urea has been demonstrated during mixed cultures between allograft donor and recipient leukocytes. This phenomenon may also be observed during primary MLC (i.e, without previous allograft) but to a lesser degree. This increased production of urea during MLC results from an increase of arginase activity in spleen cell population(s) resulting in an increased arginine transformation into urea and ornithine, as demonstrated by the release of an amount of ornithine equivalent to that of urea in the culture supernatant."} {"id": "PMID:161746", "title": "Report of a working group for the European Pharmacopoeia. Collaborative assay on human albumin of different origin.", "content": "A collaborative assay was conducted by 9 laboratories on 31 samples of human albumin which were in clinical use. It was the object of the study to establish test systems which would differentiate between albumins of venous or placental origin. The properties examined for this purpose were: appearance, total protein, haem, polymers, alkaline phosphatase and blood group substances. Additional tests such as for beta-thromboglobulin and citrate were included; pyrogenicity, however, was excluded because this was under study for all plasma proteins at that time. Results obtained were in satisfactory agreement both between laboratories and between samples. They, therefore, enabled the verification of a number of correlations in the test systems. The evaluation did not allow, however, the differentiation of the samples in relation to their origin. The results were, therefore, regarded as a tool to define the upper limits of acceptance for human albumins corresponding to the quality prescribed by the European Pharmacopoeia.", "contents": "Report of a working group for the European Pharmacopoeia. Collaborative assay on human albumin of different origin. A collaborative assay was conducted by 9 laboratories on 31 samples of human albumin which were in clinical use. It was the object of the study to establish test systems which would differentiate between albumins of venous or placental origin. The properties examined for this purpose were: appearance, total protein, haem, polymers, alkaline phosphatase and blood group substances. Additional tests such as for beta-thromboglobulin and citrate were included; pyrogenicity, however, was excluded because this was under study for all plasma proteins at that time. Results obtained were in satisfactory agreement both between laboratories and between samples. They, therefore, enabled the verification of a number of correlations in the test systems. The evaluation did not allow, however, the differentiation of the samples in relation to their origin. The results were, therefore, regarded as a tool to define the upper limits of acceptance for human albumins corresponding to the quality prescribed by the European Pharmacopoeia."} {"id": "PMID:161749", "title": "Isolation and characterization of temperature-sensitive respiratory mutants of Neurospora crassa.", "content": "Filtration-enrichment and inositol-less death methods of mutant isolation, coupled with a screen for cyanide-insensitive respiration, proved to be highly efficient methods for isolating temperature-sensitive (ts) nuclear Neurospora mutants having defective respiration. Eighteen different ts respiratory mutants have been isolated. Most of them are pleiotropic and defective in one or more of the following phenotypes: cytochrome aa3, b, and c (individual or multiple defects); oligomycin inhibition of ATPase activity; respiration and its inhibition by KCN and salicyl hydroxamic acid; and growth rates in liquid and solid media at 25 degrees and 38 degrees. Among these mutants are the first cytochrome c mutant of Neurospora and an extranuclear ts ATPase mutant. An added bonus was the fact that over half of the mutants were affected either in ribosome assembly or in protein synthesis in the mitochondrion. We have yet to find any mutants completely lacking activities associated with the respiratory chain. However, the wide spectrum of mutants isolated here, along with those currently available, constitutes a considerable resource for investigating respiration in obligate aerobes.", "contents": "Isolation and characterization of temperature-sensitive respiratory mutants of Neurospora crassa. Filtration-enrichment and inositol-less death methods of mutant isolation, coupled with a screen for cyanide-insensitive respiration, proved to be highly efficient methods for isolating temperature-sensitive (ts) nuclear Neurospora mutants having defective respiration. Eighteen different ts respiratory mutants have been isolated. Most of them are pleiotropic and defective in one or more of the following phenotypes: cytochrome aa3, b, and c (individual or multiple defects); oligomycin inhibition of ATPase activity; respiration and its inhibition by KCN and salicyl hydroxamic acid; and growth rates in liquid and solid media at 25 degrees and 38 degrees. Among these mutants are the first cytochrome c mutant of Neurospora and an extranuclear ts ATPase mutant. An added bonus was the fact that over half of the mutants were affected either in ribosome assembly or in protein synthesis in the mitochondrion. We have yet to find any mutants completely lacking activities associated with the respiratory chain. However, the wide spectrum of mutants isolated here, along with those currently available, constitutes a considerable resource for investigating respiration in obligate aerobes."} {"id": "PMID:161750", "title": "Genetics of arginine biosynthesis in Neurospora crassa.", "content": "A large number of arginine-requiring mutants of Neurospora was isolated, using a strain already partially impaired in an enzyme of the pathway. Among the mutants, all previously described loci, except one, were represented, and several new loci were defined and mapped. Four groups of mutants were of particular interest. First, the large group of arg-6 mutants, when tested for intragenic complementation, suggested a bifunctional gene, possibly controlling two steps in ornithine synthesis. This is consistent with the limited enzymic information about this locus. Second, the arg-13 locus was represented by 14 new mutants. All five tested were quite leaky, suggesting that the function controlled by this gene can be carried out to a limited extent spontaneously or by another gene product. Third, a new locus, arg-14, was defined. It controls a step in ornithine syntheses. It lies in a 1 to 2 map-unit interval between arg-2 and pyr-3 on LG IVR, as shown by mapping in relation to translocation breakpoints. Fourth, a second new locus whose mutants render the partial mutation in starting material auxotrophic was defined and mapped near the centromere of LG VIL. These new mutants are unable to derepress enzymes of the pathway and may qualify as regulatory mutants.", "contents": "Genetics of arginine biosynthesis in Neurospora crassa. A large number of arginine-requiring mutants of Neurospora was isolated, using a strain already partially impaired in an enzyme of the pathway. Among the mutants, all previously described loci, except one, were represented, and several new loci were defined and mapped. Four groups of mutants were of particular interest. First, the large group of arg-6 mutants, when tested for intragenic complementation, suggested a bifunctional gene, possibly controlling two steps in ornithine synthesis. This is consistent with the limited enzymic information about this locus. Second, the arg-13 locus was represented by 14 new mutants. All five tested were quite leaky, suggesting that the function controlled by this gene can be carried out to a limited extent spontaneously or by another gene product. Third, a new locus, arg-14, was defined. It controls a step in ornithine syntheses. It lies in a 1 to 2 map-unit interval between arg-2 and pyr-3 on LG IVR, as shown by mapping in relation to translocation breakpoints. Fourth, a second new locus whose mutants render the partial mutation in starting material auxotrophic was defined and mapped near the centromere of LG VIL. These new mutants are unable to derepress enzymes of the pathway and may qualify as regulatory mutants."} {"id": "PMID:161751", "title": "Genetic control of phosphorus assimilation in Neurospora crassa: dose-dependent dominance and recessiveness in constitutive mutants.", "content": "Mutants called nuc-1c, constitutive for alkaline phosphatase synthesis, were isolated and mapped very close to nuc-1 mutants in which this enzyme is not expressed. nuc-1 is epistatic to nuc-1c. nuc-1c acts only if it is cis to normal nuc-1 function. The preparation of partial diploids heterozygous for various nuc-1 alleles is described; nuc-1c is dominant to nuc-1+, which in turn is dominant to nuc-1. In heterocaryons with nuc-1+, nuc-1c is dominant when it is present in high proportion, but essentially recessive if it is present in low proportions. In heterocaryons with nuc-1, nuc-1c is again dominant when present in high proportions, but in low proportions it \"complements\" to give essentially normal repressibility. A model of regulation consistent with these findings is presented.", "contents": "Genetic control of phosphorus assimilation in Neurospora crassa: dose-dependent dominance and recessiveness in constitutive mutants. Mutants called nuc-1c, constitutive for alkaline phosphatase synthesis, were isolated and mapped very close to nuc-1 mutants in which this enzyme is not expressed. nuc-1 is epistatic to nuc-1c. nuc-1c acts only if it is cis to normal nuc-1 function. The preparation of partial diploids heterozygous for various nuc-1 alleles is described; nuc-1c is dominant to nuc-1+, which in turn is dominant to nuc-1. In heterocaryons with nuc-1+, nuc-1c is dominant when it is present in high proportion, but essentially recessive if it is present in low proportions. In heterocaryons with nuc-1, nuc-1c is again dominant when present in high proportions, but in low proportions it \"complements\" to give essentially normal repressibility. A model of regulation consistent with these findings is presented."} {"id": "PMID:161756", "title": "Elicitation of anti-leukemia cytotoxic responses.", "content": "We have presented the rationale for the in vitro approaches that we have taken for generating cytotoxic lymphocytes capable of lysing autologous leukemia cells or leukemia cells from HLA identical siblings. Two different approaches have been used, both of which are based on earlier findings concerning the antigenic and cellular interactions involved in the generation of strong cytotoxic responses to alloantigens in mixed leukocyte culture.", "contents": "Elicitation of anti-leukemia cytotoxic responses. We have presented the rationale for the in vitro approaches that we have taken for generating cytotoxic lymphocytes capable of lysing autologous leukemia cells or leukemia cells from HLA identical siblings. Two different approaches have been used, both of which are based on earlier findings concerning the antigenic and cellular interactions involved in the generation of strong cytotoxic responses to alloantigens in mixed leukocyte culture."} {"id": "PMID:161758", "title": "Impact of specific immunotherapy in acute myelocytic leukemia.", "content": "Our studies clearly show that significantly longer remission duration was attained in groups of AML patients immunized with neuraminidase treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase treated myeloblasts plus MER. IT is clear that MER, albeit apparently active alone in certain other clinical studies impairs the immunotherapeutic value of neuraminidase treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunological tests results reflect the host's immunological status in each arm of the protocol and correlate well with the duration of remission achieved with specific vs. combination of specific plus adjuvant immunotherapy.", "contents": "Impact of specific immunotherapy in acute myelocytic leukemia. Our studies clearly show that significantly longer remission duration was attained in groups of AML patients immunized with neuraminidase treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase treated myeloblasts plus MER. IT is clear that MER, albeit apparently active alone in certain other clinical studies impairs the immunotherapeutic value of neuraminidase treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunological tests results reflect the host's immunological status in each arm of the protocol and correlate well with the duration of remission achieved with specific vs. combination of specific plus adjuvant immunotherapy."} {"id": "PMID:161761", "title": "[Study on mucopolysaccharides in human lung carcinoma tissue--characteristics in histological types (author's transl)].", "content": "The mucopolysaccharides were prepared from human lung carcinomas of three histologically different types and the control tissue by exhaustive proteolytic digestion, quaternary ammonium chloride fractionation and column chromatography on Dowex 1 (Cl-). They were identified by chemical, enzymic and electrophoretic methods, as hyaluronic acid (HA), chondroitin sulfate (ChS), dermatan sulfate (DS), heparan sulfate (HS) and over-sulfated ChS and/or DS. Qualitatively they were not differed in tumor and normal tissues. However, the amounts of whole mucopolysaccharide were much increased in carcinomas than those of normal control in order of squamous cell carcinoma greater than small cell undifferentiated carcinoma greater than or equal to adenocarcinoma. The increment of mucopolysaccharide contents in carcinoma are largely due to increased amounts of HA and ChS. Carcinoma-type characteristic pattern was also demonstrated in terms of relative amounts of non-sulfated (HA) and sulfated (ChS, DS, HS) mucopolysaccharides: In squamous cell carcinoma and adenocarcinoma sulfated mucopolysaccharides were predominant (73 to 78% of total mucopolysaccharides), whereas in small cell undifferentiated carcinoma sulfated ones were diminished (25% of total mucopolysaccharides). In normal lung tissue sulfated mucopolysaccharide comprised 64% of total mucopolysaccharides. The presence of over-sulfated ChS and/or DS, which have not until now been found in lung tissue, was higher in carcinoma tissue as compared to the normal control. Total glycopeptides which were derived from tissue glycoproteins and not in detail characterized in this study were decreased in carcinomas of any histological types as compared to those of normal lung tissue, when expressed by hexosamine content. Biological and clinical significance of mucopolysaccharides in carcinoma state was discussed.", "contents": "[Study on mucopolysaccharides in human lung carcinoma tissue--characteristics in histological types (author's transl)]. The mucopolysaccharides were prepared from human lung carcinomas of three histologically different types and the control tissue by exhaustive proteolytic digestion, quaternary ammonium chloride fractionation and column chromatography on Dowex 1 (Cl-). They were identified by chemical, enzymic and electrophoretic methods, as hyaluronic acid (HA), chondroitin sulfate (ChS), dermatan sulfate (DS), heparan sulfate (HS) and over-sulfated ChS and/or DS. Qualitatively they were not differed in tumor and normal tissues. However, the amounts of whole mucopolysaccharide were much increased in carcinomas than those of normal control in order of squamous cell carcinoma greater than small cell undifferentiated carcinoma greater than or equal to adenocarcinoma. The increment of mucopolysaccharide contents in carcinoma are largely due to increased amounts of HA and ChS. Carcinoma-type characteristic pattern was also demonstrated in terms of relative amounts of non-sulfated (HA) and sulfated (ChS, DS, HS) mucopolysaccharides: In squamous cell carcinoma and adenocarcinoma sulfated mucopolysaccharides were predominant (73 to 78% of total mucopolysaccharides), whereas in small cell undifferentiated carcinoma sulfated ones were diminished (25% of total mucopolysaccharides). In normal lung tissue sulfated mucopolysaccharide comprised 64% of total mucopolysaccharides. The presence of over-sulfated ChS and/or DS, which have not until now been found in lung tissue, was higher in carcinoma tissue as compared to the normal control. Total glycopeptides which were derived from tissue glycoproteins and not in detail characterized in this study were decreased in carcinomas of any histological types as compared to those of normal lung tissue, when expressed by hexosamine content. Biological and clinical significance of mucopolysaccharides in carcinoma state was discussed."} {"id": "PMID:161764", "title": "Quantitation of zearalenone by gas-liquid chromatography on capillary glass columns.", "content": "A procedure is described for the quantitation of zearalenone from corn by gas-liquid chromatography. An internal standard, zearalanone, is first mixed with the finely ground corn, followed by extraction with ethyl acetate, purification by thin-layer chromatography and formation of trimethyl silyl ether (TMS) and methyl oxime (MOX) derivatives. Positive identification of zearalenone is based upon the retention times of the TMS and MOX-TMS derivatives being identical with those of the standards, comparison of chromatograms from both derivatives and characteristic twin peaks of zearalenone MOX-TMS. The detection limit of 100 parts per 10(9) zearalenone in corn could only be improved by modification of the described procedure.", "contents": "Quantitation of zearalenone by gas-liquid chromatography on capillary glass columns. A procedure is described for the quantitation of zearalenone from corn by gas-liquid chromatography. An internal standard, zearalanone, is first mixed with the finely ground corn, followed by extraction with ethyl acetate, purification by thin-layer chromatography and formation of trimethyl silyl ether (TMS) and methyl oxime (MOX) derivatives. Positive identification of zearalenone is based upon the retention times of the TMS and MOX-TMS derivatives being identical with those of the standards, comparison of chromatograms from both derivatives and characteristic twin peaks of zearalenone MOX-TMS. The detection limit of 100 parts per 10(9) zearalenone in corn could only be improved by modification of the described procedure."} {"id": "PMID:161766", "title": "[The evolution of the indications for laparoscopy between 1973 and 1977. 1,758 cases (author's transl)].", "content": "In order to avoid the misuse of laparoscopy by an unnecessary increase in the indications for the procedure the authors have reviewed the evolution of these indications in the five years between 1973 and 1977. Certain indications have stayed stable, such as chronic pain in the pelvis, masses found in the pelvis, symptoms suggestive of upper genital tract infection or of ectopic pregnancy and tubal or unexplained sterility. Stability in these indications is correct because laparoscopy and laparoscopy alone can give a precise diagnosis of the lesion and complete the clinical findings and the other methods of investigation. There are two indications which have become less frequent and these are: ovarian sterility and amenorrhoea. This is logical since more reliance has come to be placed on biological methods. Laparoscopy should be reserved in these conditions for cases where are contradictions between biological findings or where there are therapeutic failures. An increase in the indications which is very justified is in those laparoscopies which are carried out as a control of the results of tubal surgery, because there a prognosis can be given and therapy can be carried out (such as division of adhesions) and in cases of malignant tumours of the ovary which, although the procedure will give less precise information than laparotomy, has the advantage that it can be repeated from time to time.", "contents": "[The evolution of the indications for laparoscopy between 1973 and 1977. 1,758 cases (author's transl)]. In order to avoid the misuse of laparoscopy by an unnecessary increase in the indications for the procedure the authors have reviewed the evolution of these indications in the five years between 1973 and 1977. Certain indications have stayed stable, such as chronic pain in the pelvis, masses found in the pelvis, symptoms suggestive of upper genital tract infection or of ectopic pregnancy and tubal or unexplained sterility. Stability in these indications is correct because laparoscopy and laparoscopy alone can give a precise diagnosis of the lesion and complete the clinical findings and the other methods of investigation. There are two indications which have become less frequent and these are: ovarian sterility and amenorrhoea. This is logical since more reliance has come to be placed on biological methods. Laparoscopy should be reserved in these conditions for cases where are contradictions between biological findings or where there are therapeutic failures. An increase in the indications which is very justified is in those laparoscopies which are carried out as a control of the results of tubal surgery, because there a prognosis can be given and therapy can be carried out (such as division of adhesions) and in cases of malignant tumours of the ovary which, although the procedure will give less precise information than laparotomy, has the advantage that it can be repeated from time to time."} {"id": "PMID:161788", "title": "Five trypanosomatid species of insects distinguished by isoenzymes.", "content": "Blastocrithidia culicis, Crithidia deanei, Crithidia fasciculata, Herpetomonas samuelpessoai, Leptomonas seymouri and Leishmania tarentolae grown in cultures were compared by electrophoretic mobility for isoenzymes in 6 enzymes. All species were found distinct in these characteristics. Endosymbiotic C. deanei, which was identical to the aposymbiotic C. deanei in 5 enzymes, had an extra band in aspartate aminotransferase. No differences in isoenzymes were found between members of one species maintained in 2 different culture media.", "contents": "Five trypanosomatid species of insects distinguished by isoenzymes. Blastocrithidia culicis, Crithidia deanei, Crithidia fasciculata, Herpetomonas samuelpessoai, Leptomonas seymouri and Leishmania tarentolae grown in cultures were compared by electrophoretic mobility for isoenzymes in 6 enzymes. All species were found distinct in these characteristics. Endosymbiotic C. deanei, which was identical to the aposymbiotic C. deanei in 5 enzymes, had an extra band in aspartate aminotransferase. No differences in isoenzymes were found between members of one species maintained in 2 different culture media."} {"id": "PMID:161791", "title": "Polypeptide subunits of dynein 1 from sea urchin sperm flagella.", "content": "A high-resolution sodium dodecyl sulfate polyacrylamide gel electrophoresis system has been used to show the presence, in both whole sperm and isolated flagellar axonemes, of eight polypeptides migrating in the 300,000--350,000 molecular weight range characteristic of the heavy chains of dynein ATPase. Previously, only five such chains have been discernible. Extraction of isolated axonemes for 10 min at 4 degrees C with a solution containing 0.6 M NaCl, ph 7, releases a mixture of particles that separate, in sucrose density gradient centrifugation, into a major peak, dynein 1 ATPase, sedimenting at 21S and a minor peak at 12--14S. The polypeptide compositions of these two peaks are different. The dynein 1 peak, which contains most of the protein on the gradient, contains approximately equal quantities of two closely migrating heavy chains, with a small amount of a third, more slowly migrating chain; no other heavy chains appear in this peak. Two groups of smaller polypeptides (three intermediate chains, within the apparent molecular weight range 76,000--122,000 and four newly discovered light chains, within the apparent molecular weight range 14,000--24,000) cosediment with the 21S peak. The heavy chain composition of the 12--14S peak is more complex, all eight heavy chains occurring approximately the same ratios as occur in intact axonemes.", "contents": "Polypeptide subunits of dynein 1 from sea urchin sperm flagella. A high-resolution sodium dodecyl sulfate polyacrylamide gel electrophoresis system has been used to show the presence, in both whole sperm and isolated flagellar axonemes, of eight polypeptides migrating in the 300,000--350,000 molecular weight range characteristic of the heavy chains of dynein ATPase. Previously, only five such chains have been discernible. Extraction of isolated axonemes for 10 min at 4 degrees C with a solution containing 0.6 M NaCl, ph 7, releases a mixture of particles that separate, in sucrose density gradient centrifugation, into a major peak, dynein 1 ATPase, sedimenting at 21S and a minor peak at 12--14S. The polypeptide compositions of these two peaks are different. The dynein 1 peak, which contains most of the protein on the gradient, contains approximately equal quantities of two closely migrating heavy chains, with a small amount of a third, more slowly migrating chain; no other heavy chains appear in this peak. Two groups of smaller polypeptides (three intermediate chains, within the apparent molecular weight range 76,000--122,000 and four newly discovered light chains, within the apparent molecular weight range 14,000--24,000) cosediment with the 21S peak. The heavy chain composition of the 12--14S peak is more complex, all eight heavy chains occurring approximately the same ratios as occur in intact axonemes."} {"id": "PMID:161792", "title": "Effect of thiourea and substituted thioureas on dynein ATPase and on the turbidity response of Tetrahymena cilia.", "content": "The effects of thiourea and of several substituted thioureas -- phenylthiourea, alpha-naphtylthiourea, metiamide, and burimamide -- on dynein ATPase have been studied. The substituted thioureas are over 30 times more potent than thiourea in causing enhancement of 30S dynein ATPase activity and inhibition of 14S dynein ATPase activity. The effects of thiourea and phenylthiourea can be prevented by very low concentrations of beta-mercaptoethanol or dithiothreitol. Axonemal ATPase is also enhanced by the thioureas, but the reaction proceeds more slowly than for solubilized 30S dynein. Enhancement of 30S dynein ATPase by metiamide is prevented by low (approximately 1 microM) concentrations of ATP and, less effectively, by AMP-PNP, but not by AMP-PCP even though the latter is a stronger inhibitor of 30S dynein ATPase than is AMP-PNP. The thioureas inhibit the ATP-induced decrease in turbidity (measured as delta A350) of axonemal suspensions. Inhibition of the turbidity response is also prevented by low concentrations of beta-mercaptoethanol, but, in contrast to the irreversible enhancement of ATPase activity, inhibition of the turbidity response is largely reversible. The ability of 30S dynein to rebind onto twice-extracted axonemes is not changed by treatment with phenylthiourea or metiamide. These observations indicate that the thioureas react with at least two sets of SH or S--S groups on axonemes. Reaction with the group(s) on the 30S dynein causes an apparently irreversible enhancement of ATPase activity. Reaction with another group(s) causes a reversible inhibition of the turbidity response.", "contents": "Effect of thiourea and substituted thioureas on dynein ATPase and on the turbidity response of Tetrahymena cilia. The effects of thiourea and of several substituted thioureas -- phenylthiourea, alpha-naphtylthiourea, metiamide, and burimamide -- on dynein ATPase have been studied. The substituted thioureas are over 30 times more potent than thiourea in causing enhancement of 30S dynein ATPase activity and inhibition of 14S dynein ATPase activity. The effects of thiourea and phenylthiourea can be prevented by very low concentrations of beta-mercaptoethanol or dithiothreitol. Axonemal ATPase is also enhanced by the thioureas, but the reaction proceeds more slowly than for solubilized 30S dynein. Enhancement of 30S dynein ATPase by metiamide is prevented by low (approximately 1 microM) concentrations of ATP and, less effectively, by AMP-PNP, but not by AMP-PCP even though the latter is a stronger inhibitor of 30S dynein ATPase than is AMP-PNP. The thioureas inhibit the ATP-induced decrease in turbidity (measured as delta A350) of axonemal suspensions. Inhibition of the turbidity response is also prevented by low concentrations of beta-mercaptoethanol, but, in contrast to the irreversible enhancement of ATPase activity, inhibition of the turbidity response is largely reversible. The ability of 30S dynein to rebind onto twice-extracted axonemes is not changed by treatment with phenylthiourea or metiamide. These observations indicate that the thioureas react with at least two sets of SH or S--S groups on axonemes. Reaction with the group(s) on the 30S dynein causes an apparently irreversible enhancement of ATPase activity. Reaction with another group(s) causes a reversible inhibition of the turbidity response."} {"id": "PMID:161796", "title": "[Usefulness of questionnaires in detection of early symptoms of sciatica and related pain syndromes of the lumbosacral region and determination of their incidence among workers of textile industry].", "content": "The study was aimed at the determination of sciatica case rate among cotton industry workers based on inquiry. Two questionnaires for detecting complaints typical of sciatica were developed. 2463 weavers and 3083 spinners were examined. A comparative group involved 978 shop attendants and 593 office workers. It was found out that pains characteristic of sciatica were experienced by 45% weavers, 43% shop attendants, 29.2% spinners, and 16% office workers. Results of physical examinations in randomly selected cases corresponded in 97% with the questionnaire data. In most cases pains resulted from overloading of the lower section of the vertebral column.", "contents": "[Usefulness of questionnaires in detection of early symptoms of sciatica and related pain syndromes of the lumbosacral region and determination of their incidence among workers of textile industry]. The study was aimed at the determination of sciatica case rate among cotton industry workers based on inquiry. Two questionnaires for detecting complaints typical of sciatica were developed. 2463 weavers and 3083 spinners were examined. A comparative group involved 978 shop attendants and 593 office workers. It was found out that pains characteristic of sciatica were experienced by 45% weavers, 43% shop attendants, 29.2% spinners, and 16% office workers. Results of physical examinations in randomly selected cases corresponded in 97% with the questionnaire data. In most cases pains resulted from overloading of the lower section of the vertebral column."} {"id": "PMID:161797", "title": "Membrane changes during germination of Bacillus megaterium KM spores.", "content": "Bacillus megaterium KM dormant spore inner membrane ATPase exhibits a ten-fold increase in specific activity during the first 10 min of germination in the absence of protein synthesis. During this time period both in the presence and absence of chloramphenicol extensive proteolysis of spore inner membrane takes place, which results in degradation of approximately half of the membrane protein. Polyacrylamide gel electrophoresis reveals the extent and selectivity of this degradation of inner membrane protein.", "contents": "Membrane changes during germination of Bacillus megaterium KM spores. Bacillus megaterium KM dormant spore inner membrane ATPase exhibits a ten-fold increase in specific activity during the first 10 min of germination in the absence of protein synthesis. During this time period both in the presence and absence of chloramphenicol extensive proteolysis of spore inner membrane takes place, which results in degradation of approximately half of the membrane protein. Polyacrylamide gel electrophoresis reveals the extent and selectivity of this degradation of inner membrane protein."} {"id": "PMID:161798", "title": "Permeability of muscle spindle capillaries and capsule.", "content": "The permeability of capillaries in rabbit muscle spindles, intramuscular nerves, and extrafusal muscle to intraaortically infused horseradish peroxidase (HRP) was studied. The permeability of the capsule cells of the muscle spindles was also examined. Immediately following the infusion of HRP, most extrafusal capillaries contained a dense accumulation of HRP reaction product, which began to escape into the surrounding extracellular space within 2-3 min. In contrast, the concentration of HRP in the intrafusal and endoneurial capillaries was much lower than that in extrafusal capillaries, and HRP was never found outside the former vessels. In addition, HRP never completely penetrated through the spindle capsule from the extracellular into the periaxial space, although it was regularly found between the outer two or three layers of capsule cells. The results indicate that the permeability characteristics of the muscle spindle capillaries and capsule to the tracer protein HRP are very similar to those of capillaries in peripheral nerve.", "contents": "Permeability of muscle spindle capillaries and capsule. The permeability of capillaries in rabbit muscle spindles, intramuscular nerves, and extrafusal muscle to intraaortically infused horseradish peroxidase (HRP) was studied. The permeability of the capsule cells of the muscle spindles was also examined. Immediately following the infusion of HRP, most extrafusal capillaries contained a dense accumulation of HRP reaction product, which began to escape into the surrounding extracellular space within 2-3 min. In contrast, the concentration of HRP in the intrafusal and endoneurial capillaries was much lower than that in extrafusal capillaries, and HRP was never found outside the former vessels. In addition, HRP never completely penetrated through the spindle capsule from the extracellular into the periaxial space, although it was regularly found between the outer two or three layers of capsule cells. The results indicate that the permeability characteristics of the muscle spindle capillaries and capsule to the tracer protein HRP are very similar to those of capillaries in peripheral nerve."} {"id": "PMID:161799", "title": "Type III glycogenosis with multicore structures.", "content": "A case of an infantile type III glycogenosis (Forbes disease), confirmed by morphologic and biochemical studies, had light-microscopic, histochemical, and electron-microscopic evidence of multicore structures and type 1 fiber predominance with hypotrophy. This association is discussed with relation to the unusual clinical findings. The authors conclude that two distinct disease entities--Forbes disease and multicore myopathy--may coexist.", "contents": "Type III glycogenosis with multicore structures. A case of an infantile type III glycogenosis (Forbes disease), confirmed by morphologic and biochemical studies, had light-microscopic, histochemical, and electron-microscopic evidence of multicore structures and type 1 fiber predominance with hypotrophy. This association is discussed with relation to the unusual clinical findings. The authors conclude that two distinct disease entities--Forbes disease and multicore myopathy--may coexist."} {"id": "PMID:161804", "title": "Blepharoconjunctivitis: a side effect of 13-cis-retinoic acid therapy for dermatologic diseases.", "content": "Blepharoconjunctivitis developed as a side-effect of treatment of patients with basal cell carcinomas, keratinizing dermatoses, and cystic acne with oral 13-cis-retinoic acid. Forty-two of the 97 dermatologic patients had signs and symptoms of blepharoconjunctivitis that were dose related and abated one week after discontinuation of the medication. About half of the patients had a history of similar symptoms prior to treatment. Staphylococcus aureus was present in eye cultures of 73% to 79% of the patients, whether symptomatic or not. Patients whose clinical appearance was that of staphylococcal blepharoconjunctivitis and whose cultures grew S aureus were successfully treated with topical erythromycin ointment to the lids even while being treated with the 13-cis-retinoic acid.", "contents": "Blepharoconjunctivitis: a side effect of 13-cis-retinoic acid therapy for dermatologic diseases. Blepharoconjunctivitis developed as a side-effect of treatment of patients with basal cell carcinomas, keratinizing dermatoses, and cystic acne with oral 13-cis-retinoic acid. Forty-two of the 97 dermatologic patients had signs and symptoms of blepharoconjunctivitis that were dose related and abated one week after discontinuation of the medication. About half of the patients had a history of similar symptoms prior to treatment. Staphylococcus aureus was present in eye cultures of 73% to 79% of the patients, whether symptomatic or not. Patients whose clinical appearance was that of staphylococcal blepharoconjunctivitis and whose cultures grew S aureus were successfully treated with topical erythromycin ointment to the lids even while being treated with the 13-cis-retinoic acid."} {"id": "PMID:161807", "title": "[Synthetic inhibitors of serine proteinases. Part 21: Studies on the structure-activity relationships in bisamidines (author's transl)].", "content": "The antitrypsin, antiplasmin and antithrombin activities of bis(amidinobenzylidene)- and bis(amidinobenzyl)cycloalkanones are not markedly affected if the amidino group is substituted by an uncharged residue (H, OCH3, Cl, Br, NO2). In contrast, mono(amidinobenzylidene)cycloalkanones exhibit considerably lower inhibitory activities than the compounds of the abovementioned classes of substances. From the results obtained it is concluded that the second aromatic residue and not the second basic amidino group is decisive of the potent inhibitory action of the bisamidino derivatives.", "contents": "[Synthetic inhibitors of serine proteinases. Part 21: Studies on the structure-activity relationships in bisamidines (author's transl)]. The antitrypsin, antiplasmin and antithrombin activities of bis(amidinobenzylidene)- and bis(amidinobenzyl)cycloalkanones are not markedly affected if the amidino group is substituted by an uncharged residue (H, OCH3, Cl, Br, NO2). In contrast, mono(amidinobenzylidene)cycloalkanones exhibit considerably lower inhibitory activities than the compounds of the abovementioned classes of substances. From the results obtained it is concluded that the second aromatic residue and not the second basic amidino group is decisive of the potent inhibitory action of the bisamidino derivatives."} {"id": "PMID:161816", "title": "Rat mixed lymphocyte culture: optimization of culture conditions.", "content": "We have systematically analysed the various parameters of rat mixed lymphocyte culture (MLC), aiming at defining optimal conditions in analytical (micro) MLC and at the production of maximal numbers of blast cells in preparative (maxi) MLC. Treatment of both responder and stimulator cells, or at least the responder cells, with N-acyl-neuraminidase allowed a good and reproducible analytical MLC response. Responses with a maximal resolution between the stimulated versus nonstimulated control cultures were obtained in the presence of rat sera, BN serum being superior to Lewis and AO serum in supporting the response. Rat sera derived from DA and HO strains, fetal calf serum, and human serum were not good. Spleen cells, lymph node cells, and density-separated blood leucocytes were good responders, and spleen cells were good stimulators, provided the spleen cells were prepurified from most of the phagocytic cells with iron powder plus magnet. Similar culture conditions were applicable also for the maxi-MLC assay. The number of blast cells generated from a single spleen could, however, be increased by a factor of 10, if the responder cell donor was primed intravenously with 10 x 10(6) stimulator-strain spleen cells 72 h before being killed. The responses both in the non-primed and in the primed cultures were specific, since the background stimulation was negligible and the cytotoxic effect by the primed cells in the cell-mediated lysis assay was immunologically specific.", "contents": "Rat mixed lymphocyte culture: optimization of culture conditions. We have systematically analysed the various parameters of rat mixed lymphocyte culture (MLC), aiming at defining optimal conditions in analytical (micro) MLC and at the production of maximal numbers of blast cells in preparative (maxi) MLC. Treatment of both responder and stimulator cells, or at least the responder cells, with N-acyl-neuraminidase allowed a good and reproducible analytical MLC response. Responses with a maximal resolution between the stimulated versus nonstimulated control cultures were obtained in the presence of rat sera, BN serum being superior to Lewis and AO serum in supporting the response. Rat sera derived from DA and HO strains, fetal calf serum, and human serum were not good. Spleen cells, lymph node cells, and density-separated blood leucocytes were good responders, and spleen cells were good stimulators, provided the spleen cells were prepurified from most of the phagocytic cells with iron powder plus magnet. Similar culture conditions were applicable also for the maxi-MLC assay. The number of blast cells generated from a single spleen could, however, be increased by a factor of 10, if the responder cell donor was primed intravenously with 10 x 10(6) stimulator-strain spleen cells 72 h before being killed. The responses both in the non-primed and in the primed cultures were specific, since the background stimulation was negligible and the cytotoxic effect by the primed cells in the cell-mediated lysis assay was immunologically specific."} {"id": "PMID:161817", "title": "Rheumatoid synovial lymphocytes lack concanavalin-A-activated suppressor cell activity.", "content": "Synovial lymphocytes eluted by enzyme treatment from eleven patients with rheumatoid arthritis (RA) were investigated for the presence of concanavalin A (Con A)-activated suppressor cell activity as compared with that of peripheral blood lymphocytes of twenty normal donors. In addition, two patients with psoriatic arthritis and juvenile rheumatoid arthritis (JRA) were also investigated. Synovial lymphocytes from the eleven RA patients showed a mean augmentation of 28 +/- 13.30, and thus clearly lacked suppressor activity, whereas the mean suppression in the lymphocytes from the twenty normal donors was 13 +/- 14.40. Synovial lymphocytes from one patient with JRA and one with psoriatic arthritis showed a normal suppressor activity.", "contents": "Rheumatoid synovial lymphocytes lack concanavalin-A-activated suppressor cell activity. Synovial lymphocytes eluted by enzyme treatment from eleven patients with rheumatoid arthritis (RA) were investigated for the presence of concanavalin A (Con A)-activated suppressor cell activity as compared with that of peripheral blood lymphocytes of twenty normal donors. In addition, two patients with psoriatic arthritis and juvenile rheumatoid arthritis (JRA) were also investigated. Synovial lymphocytes from the eleven RA patients showed a mean augmentation of 28 +/- 13.30, and thus clearly lacked suppressor activity, whereas the mean suppression in the lymphocytes from the twenty normal donors was 13 +/- 14.40. Synovial lymphocytes from one patient with JRA and one with psoriatic arthritis showed a normal suppressor activity."} {"id": "PMID:161818", "title": "Polyclonal antibody secretion induced in human mixed lymphocyte cultures.", "content": "In mixed leucocyte culture (MLC), using human spleen cells or thoracic duct lymphocytes, antibody secretion was induced, measured as plaque-forming cells (PFC) in a haemolysis-in-gel assay with fluorescein isothiocyanate (FITC)-coupled sheep erythrocytes (SRBC) as targets. Peak antibody secretion was seen on day 5. Using protein-A-coupled SRBC as targets and developing antisera, antibody secretion in MLC was found to be of IgM, IgG and IgA type. There was no correlation between the number of PFC against FITC-SRBC in MLC and DNA synthesis. Supernatants from MLC failed to induce antibody secretion.", "contents": "Polyclonal antibody secretion induced in human mixed lymphocyte cultures. In mixed leucocyte culture (MLC), using human spleen cells or thoracic duct lymphocytes, antibody secretion was induced, measured as plaque-forming cells (PFC) in a haemolysis-in-gel assay with fluorescein isothiocyanate (FITC)-coupled sheep erythrocytes (SRBC) as targets. Peak antibody secretion was seen on day 5. Using protein-A-coupled SRBC as targets and developing antisera, antibody secretion in MLC was found to be of IgM, IgG and IgA type. There was no correlation between the number of PFC against FITC-SRBC in MLC and DNA synthesis. Supernatants from MLC failed to induce antibody secretion."} {"id": "PMID:161820", "title": "Oligomycin-resistant mitochondrial ATPase from mouse fibroblasts.", "content": "Fourteen oligomycin-resistant LM(TK-) clones were isolated following the mutagenesis of minicells. In the absence of oligomycin, the mutants grew with population doubling times similar to that of the wild type (1 day). In 3 or 5 microgram oligomycin/ml the doubling times of the mutants were 1.2-2.5 days. Both stable and unstable classes were represented among the oligomycin-resistant mutants. Mitochondrial ATPase activities of the mutants were 1.3-1130 times more resistant to oligomycin than the wild type. The mitochondrial ATPase of OLI 14 was found to be bound firmly to the mitochondrial membrane, showed no alteration in the pH optimum compared to wild-type, and exhibited increased resistance to DCCD and venturicidin. These results are consistent with the conclusion that oligomycin resistance in these mutants results from altered mitochondrial ATPase.", "contents": "Oligomycin-resistant mitochondrial ATPase from mouse fibroblasts. Fourteen oligomycin-resistant LM(TK-) clones were isolated following the mutagenesis of minicells. In the absence of oligomycin, the mutants grew with population doubling times similar to that of the wild type (1 day). In 3 or 5 microgram oligomycin/ml the doubling times of the mutants were 1.2-2.5 days. Both stable and unstable classes were represented among the oligomycin-resistant mutants. Mitochondrial ATPase activities of the mutants were 1.3-1130 times more resistant to oligomycin than the wild type. The mitochondrial ATPase of OLI 14 was found to be bound firmly to the mitochondrial membrane, showed no alteration in the pH optimum compared to wild-type, and exhibited increased resistance to DCCD and venturicidin. These results are consistent with the conclusion that oligomycin resistance in these mutants results from altered mitochondrial ATPase."} {"id": "PMID:161815", "title": "Progress in fibrinolysis.", "content": "This review deals with aspects of fibrinolysis in which significant developments have taken place in the last few years. The structural changes of plasminogen during its activation are now identified precisely; the recent description of a thrombotic tendency in a kindred characterized by a defect of this protein emphasizes its important role in the homeostatic balance. Several activators of plasminogen are now identified; some of them, such as tissue and vascular activators, appear to have an important role in physiology and pathology. The recent characterizations of the alpha 2-antiplasmin and of antiactivators have widened our understanding of the inhibitors of fibrinolysis: a defect of the plasmin inhibitor seems to be associated with an haemorrhagic tendency, whereas high antiactivator levels were encountered in thrombotic conditions. The clinical use of fibrinolytic agents appears to be promising in conditions such as recurrent deep vein thrombosis and in the post-phlebitic syndrome. Thrombolytic therapy with urokinase or streptokinase appears to have elective indications in patients with acute deep vein thrombosis and massive life-threatening pulmonary embolism.", "contents": "Progress in fibrinolysis. This review deals with aspects of fibrinolysis in which significant developments have taken place in the last few years. The structural changes of plasminogen during its activation are now identified precisely; the recent description of a thrombotic tendency in a kindred characterized by a defect of this protein emphasizes its important role in the homeostatic balance. Several activators of plasminogen are now identified; some of them, such as tissue and vascular activators, appear to have an important role in physiology and pathology. The recent characterizations of the alpha 2-antiplasmin and of antiactivators have widened our understanding of the inhibitors of fibrinolysis: a defect of the plasmin inhibitor seems to be associated with an haemorrhagic tendency, whereas high antiactivator levels were encountered in thrombotic conditions. The clinical use of fibrinolytic agents appears to be promising in conditions such as recurrent deep vein thrombosis and in the post-phlebitic syndrome. Thrombolytic therapy with urokinase or streptokinase appears to have elective indications in patients with acute deep vein thrombosis and massive life-threatening pulmonary embolism."} {"id": "PMID:161827", "title": "Effects of urinary organic macromolecules on crystallization of calcium oxalate: enhancement of nucleation.", "content": "The urine of normal persons, as well as that of stone formers, contains inhibitors to crystallization of calcium oxalate. To ascertain differences, if any, between these 2 groups we measured nucleation rate, growth rate and total mass produced in an analytic system with 5% urine added to 95% synthetic urine that did not contain large organic molecules. We also observed the effects of addition of uromucoid to the synthetic solution. Normal urine and stone-forming urine contained significant inhibitors to total mass of calcium oxalate dihydrate crystals precipitated but total crystal mass was not significantly different between the 2 groups. Growth rate was significantly less in experiments with the urine of stone formers. The other major difference found in stone-forming urine was significant enhancement of nucleation rate when compared to normal urine. Since addition of uromucoid produced these same growth inhibition and nucleation enhancement effects but did not affect total crystal mass, we hypothesize that uromucoid has an important part in producing the differences noted between normal and stone-forming urine.", "contents": "Effects of urinary organic macromolecules on crystallization of calcium oxalate: enhancement of nucleation. The urine of normal persons, as well as that of stone formers, contains inhibitors to crystallization of calcium oxalate. To ascertain differences, if any, between these 2 groups we measured nucleation rate, growth rate and total mass produced in an analytic system with 5% urine added to 95% synthetic urine that did not contain large organic molecules. We also observed the effects of addition of uromucoid to the synthetic solution. Normal urine and stone-forming urine contained significant inhibitors to total mass of calcium oxalate dihydrate crystals precipitated but total crystal mass was not significantly different between the 2 groups. Growth rate was significantly less in experiments with the urine of stone formers. The other major difference found in stone-forming urine was significant enhancement of nucleation rate when compared to normal urine. Since addition of uromucoid produced these same growth inhibition and nucleation enhancement effects but did not affect total crystal mass, we hypothesize that uromucoid has an important part in producing the differences noted between normal and stone-forming urine."} {"id": "PMID:161828", "title": "[Total serum protein and the protein spectrum of sheep and lambs after experimental percutaneous invasion by Bunostomum trigonosephalum].", "content": "Serum proteins and their fractions in sheep and lambs following experimental B. trigonocephalum percutaneous invasion were investigated. It was established that total serum protein and albumen reduction as well as beta- and gamma-globulin enhancement occur following the invasion. These changes were observed on the 50th day post invasion, but they were most pronounced after clinical symptoms of Bunostomosis appeared. The albumen-globulin coefficient was considerably reduced post invasion. All changes described were more pronounced in lambs as compared to sheep.", "contents": "[Total serum protein and the protein spectrum of sheep and lambs after experimental percutaneous invasion by Bunostomum trigonosephalum]. Serum proteins and their fractions in sheep and lambs following experimental B. trigonocephalum percutaneous invasion were investigated. It was established that total serum protein and albumen reduction as well as beta- and gamma-globulin enhancement occur following the invasion. These changes were observed on the 50th day post invasion, but they were most pronounced after clinical symptoms of Bunostomosis appeared. The albumen-globulin coefficient was considerably reduced post invasion. All changes described were more pronounced in lambs as compared to sheep."} {"id": "PMID:161830", "title": "Acne.", "content": "The cause of acne is still obscure, but genetic predisposition, sebaceous overactivity, overgrowth of bacterial flora and exposure to comedogenic substances are all significant factors. Acne lesions occur mainly in sebaceous follicles, which are characterized by deep follicular canals and large sebaceous glands. The associated seborrhea is not due to a circulatory excess of androgens but may be caused by a local amplification of androgenic activity. This, in turn, may be due to large numbers of androgen receptors and a high concentration of enzymes such as 17beta-hydroxysteroid dehydrogenase, within the sebaceous gland itself. Hyperkeratosis of the retention type in the pilary infrainfundibulum obstructs the outflow of sebum and keratin flakes. This favors the proliferation of Propionibacterium acnes which may initiate inflammation in microcomedos and lead to formation of pustules, papules or nodules. Topical therapy with tretinoin, benzoyl peroxide and antibiotics such as clindamycin is widely used today. Oral tetracyclines and other chemotherapeutic agents remain necessary in severe cases.", "contents": "Acne. The cause of acne is still obscure, but genetic predisposition, sebaceous overactivity, overgrowth of bacterial flora and exposure to comedogenic substances are all significant factors. Acne lesions occur mainly in sebaceous follicles, which are characterized by deep follicular canals and large sebaceous glands. The associated seborrhea is not due to a circulatory excess of androgens but may be caused by a local amplification of androgenic activity. This, in turn, may be due to large numbers of androgen receptors and a high concentration of enzymes such as 17beta-hydroxysteroid dehydrogenase, within the sebaceous gland itself. Hyperkeratosis of the retention type in the pilary infrainfundibulum obstructs the outflow of sebum and keratin flakes. This favors the proliferation of Propionibacterium acnes which may initiate inflammation in microcomedos and lead to formation of pustules, papules or nodules. Topical therapy with tretinoin, benzoyl peroxide and antibiotics such as clindamycin is widely used today. Oral tetracyclines and other chemotherapeutic agents remain necessary in severe cases."} {"id": "PMID:161832", "title": "Microbiological production of radioisotopically labelled 16 alpha-hydroxylated steroids in trace quantities.", "content": "[14-14C]16 alpha-Hydroxy-C-18- and C-19-steroid hormones were obtained in good yields by microbiological hydroxylation of correspondingly labelled steroids by Streptomyces roseochromogenes NRRL B-1233. Trace quantities of the labelled substrates were incubated on a rotary shaker (220 rpm) at 27 degrees C. The radioactive products were chromatographically separated, identified and the radiochemical purity was established by isotopic dilution analysis. The specific activities of 16 alpha-hydroxy-steroids obtained were assumed to be the same as those of the substrates, namely, 57.5 mCi/mmole for 16 alpha-hydroxy-4-androstene-3,17-dione, 57.5 mCi/mmole for 5-androstene-3 beta,16 alpha,17 beta-triol, 57.5 mCi/mmole for 16 alpha-hydroxy-dehydroepiandrosterone, 55.7 mCi/mmole for 16 alpha-hydroxy-estrone, and 57.5 mCi/mmole for 16 alpha-hydroxy-testosterone.", "contents": "Microbiological production of radioisotopically labelled 16 alpha-hydroxylated steroids in trace quantities. [14-14C]16 alpha-Hydroxy-C-18- and C-19-steroid hormones were obtained in good yields by microbiological hydroxylation of correspondingly labelled steroids by Streptomyces roseochromogenes NRRL B-1233. Trace quantities of the labelled substrates were incubated on a rotary shaker (220 rpm) at 27 degrees C. The radioactive products were chromatographically separated, identified and the radiochemical purity was established by isotopic dilution analysis. The specific activities of 16 alpha-hydroxy-steroids obtained were assumed to be the same as those of the substrates, namely, 57.5 mCi/mmole for 16 alpha-hydroxy-4-androstene-3,17-dione, 57.5 mCi/mmole for 5-androstene-3 beta,16 alpha,17 beta-triol, 57.5 mCi/mmole for 16 alpha-hydroxy-dehydroepiandrosterone, 55.7 mCi/mmole for 16 alpha-hydroxy-estrone, and 57.5 mCi/mmole for 16 alpha-hydroxy-testosterone."} {"id": "PMID:161833", "title": "Microbial introduction of a 16 alpha-hydroxyl function into the steroid nucleus.", "content": "The introduction of a 16 alpha-hydroxyl function into the steroid nucleus was studied in resting cells of Streptomyces roseochromogenes NRRL B-1233. The oxidation product of dehydroepiandrosterone (DHEA) was identified as 16 alpha-hydroxy DHEA by using thin-layer and gas-liquid chromatography. A linear relation between cell concentration and 16 alpha-OH-DHEA formation was observed. 16 alpha-Hydroxylase showed good activity at pH 8.0 for 16 alpha-OH-DHEA formation. The enzyme showed good activity at 3.1 x 10(-4) M DHEA. The oxidation products of pregnenolone, 4-androstene-3,17-dione, estrone, and 5-androstene-3 beta,17 beta-diol as well as of other substrates were identified as the 16 alpha-hydroxy steroid, respectively. The rates of microbial 16 alpha-hydroxylation were as follows: 76.9% for DHEA, 50.4% for pregnenolone, 43.9% for 4-androstene-3,17-dione, 34.3% for estrone, and 19.6% for 5-androstene-3 beta,17 beta-diol. The organism tested catalyzes 16 alpha-hydroxylation of a wide variety of steroids.", "contents": "Microbial introduction of a 16 alpha-hydroxyl function into the steroid nucleus. The introduction of a 16 alpha-hydroxyl function into the steroid nucleus was studied in resting cells of Streptomyces roseochromogenes NRRL B-1233. The oxidation product of dehydroepiandrosterone (DHEA) was identified as 16 alpha-hydroxy DHEA by using thin-layer and gas-liquid chromatography. A linear relation between cell concentration and 16 alpha-OH-DHEA formation was observed. 16 alpha-Hydroxylase showed good activity at pH 8.0 for 16 alpha-OH-DHEA formation. The enzyme showed good activity at 3.1 x 10(-4) M DHEA. The oxidation products of pregnenolone, 4-androstene-3,17-dione, estrone, and 5-androstene-3 beta,17 beta-diol as well as of other substrates were identified as the 16 alpha-hydroxy steroid, respectively. The rates of microbial 16 alpha-hydroxylation were as follows: 76.9% for DHEA, 50.4% for pregnenolone, 43.9% for 4-androstene-3,17-dione, 34.3% for estrone, and 19.6% for 5-androstene-3 beta,17 beta-diol. The organism tested catalyzes 16 alpha-hydroxylation of a wide variety of steroids."} {"id": "PMID:161835", "title": "Structure of cerebrosides. II. Small angle X-ray diffraction study of cerasine.", "content": "Cerasine having a molecular weight of 800 differs chemically from phrenosine only in the hydroxyl group attached to the fatty acid tail which is replaced by a hydrogen atom. Nevertheless, remarkable differences between both cerebrosides are detected in the lamellae periodicities. In the range of 23--66 degrees C just one single (instead of two) structure with a similar subcell to the triclinic one component of phrenosine detected. Between 66 and 87 degrees C three new components (instead of one in phrenosine) appear. Two of the structures are similar to the two phrenosine-components at low temperature and the tilt angles of their chains with respect to the basal planes can explain the stabilizing capacity of the 201 and 301 netplanes of the paraffin-like subcells respectively. These lattice planes are parallely aligned to the surfaces of the lamellae. The long period of 58 A of component II cannot be explained in such a way. This period persists up to 105 degrees C and coexists from 87 degrees C with a new component showing a 40 A-periodicity, which cannot either be explained in the above manner. Paracrystalline distortions of the arrangement of the bilayers can be justified by orientational disorder of the galactose heads.", "contents": "Structure of cerebrosides. II. Small angle X-ray diffraction study of cerasine. Cerasine having a molecular weight of 800 differs chemically from phrenosine only in the hydroxyl group attached to the fatty acid tail which is replaced by a hydrogen atom. Nevertheless, remarkable differences between both cerebrosides are detected in the lamellae periodicities. In the range of 23--66 degrees C just one single (instead of two) structure with a similar subcell to the triclinic one component of phrenosine detected. Between 66 and 87 degrees C three new components (instead of one in phrenosine) appear. Two of the structures are similar to the two phrenosine-components at low temperature and the tilt angles of their chains with respect to the basal planes can explain the stabilizing capacity of the 201 and 301 netplanes of the paraffin-like subcells respectively. These lattice planes are parallely aligned to the surfaces of the lamellae. The long period of 58 A of component II cannot be explained in such a way. This period persists up to 105 degrees C and coexists from 87 degrees C with a new component showing a 40 A-periodicity, which cannot either be explained in the above manner. Paracrystalline distortions of the arrangement of the bilayers can be justified by orientational disorder of the galactose heads."} {"id": "PMID:161836", "title": "Determination of alpha-, beta-, and gamma-amanitin by high performance thin-layer chromatography in Amanita phalloides (Vaill. ex Fr.) secr. from various origin.", "content": "A fast, sensitive high performance thin-layer chromatographic method for the determination of alpha-, beta-, and gamma-amanitin in crude, methanolic extracts of Amanita phalloides is described. The limit of detection is 50 ng of each amanitin. With this method amanitin was determined in 24 pooled samples of Amanita phalloides, collected between 1970 and 1977 in Germany and Switzerland. The total amanitin content varied between 2010 and 7300 mg/kg dry weight and the average value was 4430 mg/kg of which 43% was alpha-amanitin, 49% beta-amanitin and 8% gamma-amanitin. The origin of the fungi hardly influenced their amanitin content: in samples collected during the same year at different sites it fluctuated within a factor of 1.7. The amanitin content of samples from the same site, but collected in different years, maximally varied within a factor of 3.7. The partial decomposition of amanitins during prolonged storage of the lyophilized samples undoubtedly contributed to this variation. Phalloidin, which was determined by conventional thin-layer-chromatography, could not be detected in a sample from 1970, whereas its concentration in material collected during 1977 amounted to 2400 mg/kg dry weight. The toxicity of the samples (LD50 of lyophilized defatted methanolic extracts intravenously for mice) varied within a factor of 2.5.", "contents": "Determination of alpha-, beta-, and gamma-amanitin by high performance thin-layer chromatography in Amanita phalloides (Vaill. ex Fr.) secr. from various origin. A fast, sensitive high performance thin-layer chromatographic method for the determination of alpha-, beta-, and gamma-amanitin in crude, methanolic extracts of Amanita phalloides is described. The limit of detection is 50 ng of each amanitin. With this method amanitin was determined in 24 pooled samples of Amanita phalloides, collected between 1970 and 1977 in Germany and Switzerland. The total amanitin content varied between 2010 and 7300 mg/kg dry weight and the average value was 4430 mg/kg of which 43% was alpha-amanitin, 49% beta-amanitin and 8% gamma-amanitin. The origin of the fungi hardly influenced their amanitin content: in samples collected during the same year at different sites it fluctuated within a factor of 1.7. The amanitin content of samples from the same site, but collected in different years, maximally varied within a factor of 3.7. The partial decomposition of amanitins during prolonged storage of the lyophilized samples undoubtedly contributed to this variation. Phalloidin, which was determined by conventional thin-layer-chromatography, could not be detected in a sample from 1970, whereas its concentration in material collected during 1977 amounted to 2400 mg/kg dry weight. The toxicity of the samples (LD50 of lyophilized defatted methanolic extracts intravenously for mice) varied within a factor of 2.5."} {"id": "PMID:161837", "title": "Radiation aggregates of insulin.", "content": "During the irradiation of aqueous solution of insulin (pH 1.8) the decrease of original insulin molecules and the formation of radiation aggregates of insulin was studied in dependence on the concentration of irradiation solution, on the doses and conditions of irradiation (oxygenated and oxygen-free atmosphere, the presence of t-butanol, addition of [14C]amino acids). From the results obtained and results published earlier it may be assumed that in irradiated solution on insulin new covalent bonds between insulin molecules are formed at tyrosyl, phenylalanyl and cystyl radicals; these radicals are formed by the action of both direct and indirect effect (at present pH 1.8 mainly of H atoms).", "contents": "Radiation aggregates of insulin. During the irradiation of aqueous solution of insulin (pH 1.8) the decrease of original insulin molecules and the formation of radiation aggregates of insulin was studied in dependence on the concentration of irradiation solution, on the doses and conditions of irradiation (oxygenated and oxygen-free atmosphere, the presence of t-butanol, addition of [14C]amino acids). From the results obtained and results published earlier it may be assumed that in irradiated solution on insulin new covalent bonds between insulin molecules are formed at tyrosyl, phenylalanyl and cystyl radicals; these radicals are formed by the action of both direct and indirect effect (at present pH 1.8 mainly of H atoms)."} {"id": "PMID:161838", "title": "Protamine and polyarginine bacteriolysis. Similarities in its mechanism with chromatin DNA picnosis.", "content": "Protamine and polyarginine had bacteriolytic effects indicating their primary sites of action as being wall components and showing bacterial diversity genetically determined. Shake-incubation was required in producing cell-lysis. Studies on Bacillus subtilis revealed a high polycation multiplicity per cell in lytic event displaying multihit lysing kinetics; bacteriolysis was inhibited by trypsin, pronase, purified polyanionic wall polysaccharide, and by dissociative actions of salt hypermolarities used in isolation of nucleic acids. The inactivation of polycation lytic abilities during bacteriolysis was accompanied by modifications in electrophoretic running of protamine and polyarginine. It is suggested as mechanism of cell-lysis, the multiple zonal surface condensations of polyanionic wall components by basic polypeptides, likely similar with chromatin DNA picnosis. This analogy is discussed.", "contents": "Protamine and polyarginine bacteriolysis. Similarities in its mechanism with chromatin DNA picnosis. Protamine and polyarginine had bacteriolytic effects indicating their primary sites of action as being wall components and showing bacterial diversity genetically determined. Shake-incubation was required in producing cell-lysis. Studies on Bacillus subtilis revealed a high polycation multiplicity per cell in lytic event displaying multihit lysing kinetics; bacteriolysis was inhibited by trypsin, pronase, purified polyanionic wall polysaccharide, and by dissociative actions of salt hypermolarities used in isolation of nucleic acids. The inactivation of polycation lytic abilities during bacteriolysis was accompanied by modifications in electrophoretic running of protamine and polyarginine. It is suggested as mechanism of cell-lysis, the multiple zonal surface condensations of polyanionic wall components by basic polypeptides, likely similar with chromatin DNA picnosis. This analogy is discussed."} {"id": "PMID:161839", "title": "Interference of L-alpha-aminooxy-beta-phenylpropionic acid with phenylalanine metabolism in buckwheat.", "content": "L-alpha-Aminooxy-beta-phenylpropionic acid (AOPP), a potent competitive inhibitor of phenylalanine ammonia-lyase (PAL), blocked light-induced phenylpropanoid synthesis in excised buckwheat hypocotyls and produced an up to 40-fold increase in the endogenous phenylalanine concentration, while the level of all other amino acids was hardly affected. After a 24 h incubation in the light in the presence of 0.3 or 1 mM AOPP phenylalanine alone constituted about 25% of the total soluble amino acids, compared to appr. 1% in the controls. In the presence of AOPP illuminated hypocotyls accumulated nearly 3 times more phenylalanine than hypocotyls kept in the dark, indicating an enhancing effect of light on the flow of carbon through the shikimate pathway. Exogenously added [14C]phenylalanine was extensively metabolized by control tissue, but accumulated in AOPP treated tissue. In the presence of AOPP radioactivity from [14C]shikimate accumulated predominantly in phenylalanine, and the flow of shikimate into tyrosine and phenylalanine was not affected by the inhibitor. Therefore, under these conditions no feedback control of phenylalanine and tyrosine synthesis from shikimate is apparent in buckwheat hypocotyls.", "contents": "Interference of L-alpha-aminooxy-beta-phenylpropionic acid with phenylalanine metabolism in buckwheat. L-alpha-Aminooxy-beta-phenylpropionic acid (AOPP), a potent competitive inhibitor of phenylalanine ammonia-lyase (PAL), blocked light-induced phenylpropanoid synthesis in excised buckwheat hypocotyls and produced an up to 40-fold increase in the endogenous phenylalanine concentration, while the level of all other amino acids was hardly affected. After a 24 h incubation in the light in the presence of 0.3 or 1 mM AOPP phenylalanine alone constituted about 25% of the total soluble amino acids, compared to appr. 1% in the controls. In the presence of AOPP illuminated hypocotyls accumulated nearly 3 times more phenylalanine than hypocotyls kept in the dark, indicating an enhancing effect of light on the flow of carbon through the shikimate pathway. Exogenously added [14C]phenylalanine was extensively metabolized by control tissue, but accumulated in AOPP treated tissue. In the presence of AOPP radioactivity from [14C]shikimate accumulated predominantly in phenylalanine, and the flow of shikimate into tyrosine and phenylalanine was not affected by the inhibitor. Therefore, under these conditions no feedback control of phenylalanine and tyrosine synthesis from shikimate is apparent in buckwheat hypocotyls."} {"id": "PMID:161840", "title": "[Molybdocene dichloride as an antitumor agent (author's transl)].", "content": "The antitumor activity of molybdocene dichloride is tested against Ehrlich ascites tumor in CF1 mice. The application of 75 of 100 mg/kg 24 h after transplantation achieves 100% tumor inhibition until day 30. Following the d0 and d1 metallocene dichlorides of titanium and vanadium, molybdocene dichloride is the first analogous d2 system revealing similar antineoplastic properties.", "contents": "[Molybdocene dichloride as an antitumor agent (author's transl)]. The antitumor activity of molybdocene dichloride is tested against Ehrlich ascites tumor in CF1 mice. The application of 75 of 100 mg/kg 24 h after transplantation achieves 100% tumor inhibition until day 30. Following the d0 and d1 metallocene dichlorides of titanium and vanadium, molybdocene dichloride is the first analogous d2 system revealing similar antineoplastic properties."} {"id": "PMID:161841", "title": "Inhibition of protein synthesis in chloroplasts from plant cells by virginiamycin.", "content": "The light-driven incorporation of amino acids by isolated spinach chloroplasts is inhibited by the M component (VM) and not by the S component (VS) of virginiamycin. This inhibitory effect is partially reversible. In chloroplast extracts, poly(U)-directed polyphenylalanine formation is strongly inhibited by VM and not by VS. The in vivo synergistic effect of VM and VS observed in bacteria and algae, does not occur in isolated chloroplasts and chloroplast extracts.", "contents": "Inhibition of protein synthesis in chloroplasts from plant cells by virginiamycin. The light-driven incorporation of amino acids by isolated spinach chloroplasts is inhibited by the M component (VM) and not by the S component (VS) of virginiamycin. This inhibitory effect is partially reversible. In chloroplast extracts, poly(U)-directed polyphenylalanine formation is strongly inhibited by VM and not by VS. The in vivo synergistic effect of VM and VS observed in bacteria and algae, does not occur in isolated chloroplasts and chloroplast extracts."} {"id": "PMID:161843", "title": "Serine transport and membrane depolarization in the liverwort Riccia fluitans.", "content": "The plasmalemma of thallus cells of the aquatic liverwort, Riccia fluitans, is reversibly depolarized by L- and D-serine. At 0.1 mM K+ in the medium, the depolarization saturates at 50 mV; half-maximal depolarization occurs at 13 microM L-serine and 30 microM D-serine, respectively. Uptake of 14C-labelled L-serine depends upon the K+ concentration and is sensitive to the membrane potential as indicated by its reduction through 1 mM sodium cyanide. We propose that serine binds to and is transported by an electrogenic carrier. However, an interaction of serine with K+ channels of the membrane seems also possible.", "contents": "Serine transport and membrane depolarization in the liverwort Riccia fluitans. The plasmalemma of thallus cells of the aquatic liverwort, Riccia fluitans, is reversibly depolarized by L- and D-serine. At 0.1 mM K+ in the medium, the depolarization saturates at 50 mV; half-maximal depolarization occurs at 13 microM L-serine and 30 microM D-serine, respectively. Uptake of 14C-labelled L-serine depends upon the K+ concentration and is sensitive to the membrane potential as indicated by its reduction through 1 mM sodium cyanide. We propose that serine binds to and is transported by an electrogenic carrier. However, an interaction of serine with K+ channels of the membrane seems also possible."} {"id": "PMID:161844", "title": "Rates of de novo synthesis of malate synthase and albumins during the very early phase of germination.", "content": "Malate synthase is synthesized de novo in the very phase of germination. Its molecular and immunological properties do not differ from those of malate synthase from fully developed cotyledons. Radioactive leucine was administered to dry seeds of cucumber, and its incorporation into proteins of cotyledons was examined after 2 days of germination. The specific radioactivity of malate synthase, purified by immunoprecipitation and electrophoresis on polyacrylamide gel, was only 1/20 the average value of the total albumin fraction. The minimal incorporation documented by the comparatively low specific activity of isolated malate synthase is discussed in relation to the large pool of malate synthase already present in dry seeds.", "contents": "Rates of de novo synthesis of malate synthase and albumins during the very early phase of germination. Malate synthase is synthesized de novo in the very phase of germination. Its molecular and immunological properties do not differ from those of malate synthase from fully developed cotyledons. Radioactive leucine was administered to dry seeds of cucumber, and its incorporation into proteins of cotyledons was examined after 2 days of germination. The specific radioactivity of malate synthase, purified by immunoprecipitation and electrophoresis on polyacrylamide gel, was only 1/20 the average value of the total albumin fraction. The minimal incorporation documented by the comparatively low specific activity of isolated malate synthase is discussed in relation to the large pool of malate synthase already present in dry seeds."} {"id": "PMID:161845", "title": "Distribution of thioredoxins in Cyanobacteria.", "content": "The presence of thioredoxin was demonstrated in 20 strains of cyanobacteria as well as in one phototrophic bacterium Rhodopseudomonas sulfidophila and in Thiobacillus denitrificans. Thioredoxin activity was not found in Cyanophora paradoxa and in Porphyridium cruentum using the thioredoxin-dependent PAPS-sulfotransferase activity from Synechococcus 6301 as assay system.", "contents": "Distribution of thioredoxins in Cyanobacteria. The presence of thioredoxin was demonstrated in 20 strains of cyanobacteria as well as in one phototrophic bacterium Rhodopseudomonas sulfidophila and in Thiobacillus denitrificans. Thioredoxin activity was not found in Cyanophora paradoxa and in Porphyridium cruentum using the thioredoxin-dependent PAPS-sulfotransferase activity from Synechococcus 6301 as assay system."} {"id": "PMID:161847", "title": "Down syndrome with XO/XX mosaicism.", "content": "A 2-month-old girl with Down syndrome was found to have 47, XX, +21/46, X, +21 mosaicism. No symptoms indicative of infantile Turner syndrome were observed.", "contents": "Down syndrome with XO/XX mosaicism. A 2-month-old girl with Down syndrome was found to have 47, XX, +21/46, X, +21 mosaicism. No symptoms indicative of infantile Turner syndrome were observed."} {"id": "PMID:161846", "title": "Estradiol and estetrol plasma levels before and after intravenous administration of dehydroepiandrosterone sulfate in normal and pathologic pregnancies.", "content": "Intravenous injections of 50 mg dehydroepiandrosterone sulfate (DHEAS) were given to 7 women with normal pregnancies and 5 with pathologic pregnancies and the serum levels of 17 beta-estradiol and estetrol were assayed before and at 15 or 30-minute intervals for three hours after the injection. All tests were carried out during the 25th to 36th week of amenorrhea. Serum estradiol rose rapidly in normal subjects and remained high to the end of the test. In patients with gestational pathology the estradiol pattern was not significantly different from that of the controls. Esterol plasma levels showed a biphasic pattern with an initial rise at 30 min. and a second rise at 90 min. in normal pregnancies, whereas in pathologic pregnancies this response was either lacking completely or was markedly reduced compared to the controls.", "contents": "Estradiol and estetrol plasma levels before and after intravenous administration of dehydroepiandrosterone sulfate in normal and pathologic pregnancies. Intravenous injections of 50 mg dehydroepiandrosterone sulfate (DHEAS) were given to 7 women with normal pregnancies and 5 with pathologic pregnancies and the serum levels of 17 beta-estradiol and estetrol were assayed before and at 15 or 30-minute intervals for three hours after the injection. All tests were carried out during the 25th to 36th week of amenorrhea. Serum estradiol rose rapidly in normal subjects and remained high to the end of the test. In patients with gestational pathology the estradiol pattern was not significantly different from that of the controls. Esterol plasma levels showed a biphasic pattern with an initial rise at 30 min. and a second rise at 90 min. in normal pregnancies, whereas in pathologic pregnancies this response was either lacking completely or was markedly reduced compared to the controls."} {"id": "PMID:161848", "title": "The effect of xenoantisera on T-lymphocyte functions in the absence of complement.", "content": "An attempt was made to determine whether xenoantisera can detect functional receptors on mouse T lymphocytes. Antisera were raised by immunizing rabbits with BALB/c thymus cells, boiled thymus homogenate, brain homogenate or bone marrow cells. Following heat inactivation these antisera were absorbed with mouse kidney and liver homogenates, and studied for their effect, in the absence of C', on the activity of murine T lymphocytes. Rabbit anti-bone marrow serum (RAB) had no effect on the mixed lymphocyte reaction (MLR) nor on cell-mediated lysis (CML). In contrast, rabbit anti-thymus serum (RAT) and anti-boiled thymus serum (RABT) inhibited strikingly, the MLR, CML, and the response to concanavalin A and phytohemagglutinin. Rabbit anti-brain serum (RABR) caused a marked increase of the proliferation of lymphocytes both in the presence or absence of various stimuli and had no effect on the CML. Absorption experiments indicated that a number of antigens are involved in the inhibitory activity of RAT. Antibodies to a T cell specific antigen interfere with the response of T lymphocytes to mitogenic stimuli, while the activity of cytotoxic T cells is inhibited by antibodies to a determinant shared by B and T lymphocytes.", "contents": "The effect of xenoantisera on T-lymphocyte functions in the absence of complement. An attempt was made to determine whether xenoantisera can detect functional receptors on mouse T lymphocytes. Antisera were raised by immunizing rabbits with BALB/c thymus cells, boiled thymus homogenate, brain homogenate or bone marrow cells. Following heat inactivation these antisera were absorbed with mouse kidney and liver homogenates, and studied for their effect, in the absence of C', on the activity of murine T lymphocytes. Rabbit anti-bone marrow serum (RAB) had no effect on the mixed lymphocyte reaction (MLR) nor on cell-mediated lysis (CML). In contrast, rabbit anti-thymus serum (RAT) and anti-boiled thymus serum (RABT) inhibited strikingly, the MLR, CML, and the response to concanavalin A and phytohemagglutinin. Rabbit anti-brain serum (RABR) caused a marked increase of the proliferation of lymphocytes both in the presence or absence of various stimuli and had no effect on the CML. Absorption experiments indicated that a number of antigens are involved in the inhibitory activity of RAT. Antibodies to a T cell specific antigen interfere with the response of T lymphocytes to mitogenic stimuli, while the activity of cytotoxic T cells is inhibited by antibodies to a determinant shared by B and T lymphocytes."} {"id": "PMID:161850", "title": "Suppressor monocytes in human disease: a review.", "content": "Suppressor monocytes have been found in a number of human diseases most of which are associated with lymphopenia and deficiences in cell mediated immunity. In our studies both quantitative and qualitative differences in monocytes were detected in certain patients with advanced Hodgkin's disease or tuberculosis. In certain patients lymphocyte activating factor production by monocytes was severely depressed in part secondary to decreased activation by suppressed T cells, although at times primary impairment of macrophage function was also probably contributory. Mononuclear cell cultures from patients with advanced Hodgkin's disease also manifested excessive prostaglandin secretion; however, the association of this with monocyte suppression and deficient LAF production was inconstant. Furthermore, reversibility of monocyte suppression could not regularly be achieved by inhibition of prostaglandin synthetase with indomethacin suggesting that excessive production of prostaglandins is unlikely to be the sole mechanism of monocyte inhibition of lymphoproliferation. It also remains to be established whether the inhibition of lymphoproliferation in vitro is important to in vivo delayed hypersensitivity or whether the mechanism is related to other macrophage effects such as tumor cytostasis and cytolysis.", "contents": "Suppressor monocytes in human disease: a review. Suppressor monocytes have been found in a number of human diseases most of which are associated with lymphopenia and deficiences in cell mediated immunity. In our studies both quantitative and qualitative differences in monocytes were detected in certain patients with advanced Hodgkin's disease or tuberculosis. In certain patients lymphocyte activating factor production by monocytes was severely depressed in part secondary to decreased activation by suppressed T cells, although at times primary impairment of macrophage function was also probably contributory. Mononuclear cell cultures from patients with advanced Hodgkin's disease also manifested excessive prostaglandin secretion; however, the association of this with monocyte suppression and deficient LAF production was inconstant. Furthermore, reversibility of monocyte suppression could not regularly be achieved by inhibition of prostaglandin synthetase with indomethacin suggesting that excessive production of prostaglandins is unlikely to be the sole mechanism of monocyte inhibition of lymphoproliferation. It also remains to be established whether the inhibition of lymphoproliferation in vitro is important to in vivo delayed hypersensitivity or whether the mechanism is related to other macrophage effects such as tumor cytostasis and cytolysis."} {"id": "PMID:161853", "title": "Inhibition of histamine methylation in vivo by the dimaprit analog, SKF Compound 91488.", "content": "The Dimaprit analog, S-[4-(N,N-dimethylamino)-butyl]isothiurea (SKF Compound 91488), which is a noncompetitive inhibitor (Ki, 0.9 microM) of histamine-N-methyltransferase in vitro, inhibited the methylation of labeled histamine in mice. When administered in combination with the diamine oxidase inhibitor, aminoguanidine, an almost complete block of histamine metabolism was observed. The inhibition was dependent on dose of drug and was apparent with doses of 50 mg/kg and greater. Since Compound 91488 is reported to have no agonist activity of its own, the drug may help to identify the actions of histamine released from endogenous stores in response to physiological and pathological stimuli.", "contents": "Inhibition of histamine methylation in vivo by the dimaprit analog, SKF Compound 91488. The Dimaprit analog, S-[4-(N,N-dimethylamino)-butyl]isothiurea (SKF Compound 91488), which is a noncompetitive inhibitor (Ki, 0.9 microM) of histamine-N-methyltransferase in vitro, inhibited the methylation of labeled histamine in mice. When administered in combination with the diamine oxidase inhibitor, aminoguanidine, an almost complete block of histamine metabolism was observed. The inhibition was dependent on dose of drug and was apparent with doses of 50 mg/kg and greater. Since Compound 91488 is reported to have no agonist activity of its own, the drug may help to identify the actions of histamine released from endogenous stores in response to physiological and pathological stimuli."} {"id": "PMID:161854", "title": "A comparative study with impromidine (SKF 92676), a potent agonist for histamine H2-receptors.", "content": "Histamine, dimaprit and impromidine caused a relaxation on the isolated cat tracheal muscle contracted by acetylcholine or serotonin. Mepyramine partially inhibited the relaxing effect of histamine without altering that of impromidine and dimaprit. Both impromidine and dimaprit produced a dose-dependent fall in perfusion pressure of the isolated perfused guinea-pig lung while histamine has a pressor effect in this preparation which reversed into a depressor one in the presence of mepyramine. Both dimaprit and impromidine also produced a fall in perfusion pressure and urine flow of the isolated perfused rabbit kidney. A rapid tachyphylaxis developed to the effect of impromidine in the kidney but not to dimaprit. A cross-tachyphylaxis was also observed between impromidine and dimaprit. The agonistic potency of impromidine was found to be very much higher than histamine and dimaprit. Metiamide has a competitive inhibitory effect against impromidine and dimaprit on the isolated perfused lung, kidney and tracheal muscle. It was concluded that impromidine is a very potent pure histamine H2-receptor agonist when compared with histamine and dimaprit on the investigated tissues.", "contents": "A comparative study with impromidine (SKF 92676), a potent agonist for histamine H2-receptors. Histamine, dimaprit and impromidine caused a relaxation on the isolated cat tracheal muscle contracted by acetylcholine or serotonin. Mepyramine partially inhibited the relaxing effect of histamine without altering that of impromidine and dimaprit. Both impromidine and dimaprit produced a dose-dependent fall in perfusion pressure of the isolated perfused guinea-pig lung while histamine has a pressor effect in this preparation which reversed into a depressor one in the presence of mepyramine. Both dimaprit and impromidine also produced a fall in perfusion pressure and urine flow of the isolated perfused rabbit kidney. A rapid tachyphylaxis developed to the effect of impromidine in the kidney but not to dimaprit. A cross-tachyphylaxis was also observed between impromidine and dimaprit. The agonistic potency of impromidine was found to be very much higher than histamine and dimaprit. Metiamide has a competitive inhibitory effect against impromidine and dimaprit on the isolated perfused lung, kidney and tracheal muscle. It was concluded that impromidine is a very potent pure histamine H2-receptor agonist when compared with histamine and dimaprit on the investigated tissues."} {"id": "PMID:161855", "title": "Therapeutic effect of beta-[1-phenyl-5-bis(beta-chloroethyl)-amino-benzimidazolyl-(2)-DL-alanin (ZIMET 3164) on immune complex nephritis of NZB hybrid mice.", "content": "Beta-[1-Phenyl-5-bis(beta-chloroethyl)-amino-benzimidazolyl-(2)]-DL-alanin (ZIMET 3164), a highly immunosuppressive but moderately cytostatic agent, was found to be able to prevent the progression of spontaneous murine immune complex nephritis in a dose-dependent fashion. For experiments, BCG-stimulated conventional female (NMRI X NZB)F1 mice suffering from rapidly progressive nephritis, BCG-stimulated and unilaterally nephrectomized (NMRI X NZB)F1 females, and (AB/Jena X NZB)F1 females characterized by a prolonged course of the disease were used. The beneficial effect was quantified by fluorescence photometry and histometry, and semiquantitatively detected by estimation of the extent of damage of individual glomerular structures when histometric methods were unsuited. Treatment of young adult animals characterized by slight to moderate glomerular lesions was more effective than of older ones with advanced nephritis. At equi-immunosuppressive dose levels ZIMET 3164 was about twice as effective as the reference substance cyclophosphamide.", "contents": "Therapeutic effect of beta-[1-phenyl-5-bis(beta-chloroethyl)-amino-benzimidazolyl-(2)-DL-alanin (ZIMET 3164) on immune complex nephritis of NZB hybrid mice. Beta-[1-Phenyl-5-bis(beta-chloroethyl)-amino-benzimidazolyl-(2)]-DL-alanin (ZIMET 3164), a highly immunosuppressive but moderately cytostatic agent, was found to be able to prevent the progression of spontaneous murine immune complex nephritis in a dose-dependent fashion. For experiments, BCG-stimulated conventional female (NMRI X NZB)F1 mice suffering from rapidly progressive nephritis, BCG-stimulated and unilaterally nephrectomized (NMRI X NZB)F1 females, and (AB/Jena X NZB)F1 females characterized by a prolonged course of the disease were used. The beneficial effect was quantified by fluorescence photometry and histometry, and semiquantitatively detected by estimation of the extent of damage of individual glomerular structures when histometric methods were unsuited. Treatment of young adult animals characterized by slight to moderate glomerular lesions was more effective than of older ones with advanced nephritis. At equi-immunosuppressive dose levels ZIMET 3164 was about twice as effective as the reference substance cyclophosphamide."} {"id": "PMID:161856", "title": "(Ca2++Mg2+)-ATPase activity of sickle cell membranes: decreased activation by red blood cell cytoplasmic activator.", "content": "Human red blood cells (RBCs) contain a cytoplasmic protein that activates membrane-bound (Ca2+ + Mg2+)-ATPase and the transport of Ca2+. The (Ca2+ + Mg2+)-ATPase of sickle cells showed a less than normal response to this activator. This was true whether the activator was obtained from normal or sickle cells. Activator present in sickle cell hemolysates fully activated the (Ca2+ + Mg2+)-ATPase of normal RBC membranes. These results demonstrate that membranes of sickle cells are defective in their response to the activator. Neither the apparent affinity for calcium nor the apparent affinity for activator was different comparing the (Ca2+ + Mg2+)-ATPase of sickle and normal membranes. Young, mature, and irreversibly sickled cells were separated by density gradient centrifugation, and membranes were prepared from each of these cell populations. No significant differences in ATPase activities were found based on cell age (density). The (Ca2+ + Mg2+)-ATPase of all populations of sickle cells showed a decreased response to the activator. Thus, it appears unlikely that the decreased response of the (Ca2+ + Mg2+)-ATPase of sickle cells is due to membrane damage caused by repeated sickling during the life-span of the cell. Reduced activation of (Ca2+ + Mg2+)-ATPase by the cytoplasmic activator may account for calcium accumulation in sickle cells.", "contents": "(Ca2++Mg2+)-ATPase activity of sickle cell membranes: decreased activation by red blood cell cytoplasmic activator. Human red blood cells (RBCs) contain a cytoplasmic protein that activates membrane-bound (Ca2+ + Mg2+)-ATPase and the transport of Ca2+. The (Ca2+ + Mg2+)-ATPase of sickle cells showed a less than normal response to this activator. This was true whether the activator was obtained from normal or sickle cells. Activator present in sickle cell hemolysates fully activated the (Ca2+ + Mg2+)-ATPase of normal RBC membranes. These results demonstrate that membranes of sickle cells are defective in their response to the activator. Neither the apparent affinity for calcium nor the apparent affinity for activator was different comparing the (Ca2+ + Mg2+)-ATPase of sickle and normal membranes. Young, mature, and irreversibly sickled cells were separated by density gradient centrifugation, and membranes were prepared from each of these cell populations. No significant differences in ATPase activities were found based on cell age (density). The (Ca2+ + Mg2+)-ATPase of all populations of sickle cells showed a decreased response to the activator. Thus, it appears unlikely that the decreased response of the (Ca2+ + Mg2+)-ATPase of sickle cells is due to membrane damage caused by repeated sickling during the life-span of the cell. Reduced activation of (Ca2+ + Mg2+)-ATPase by the cytoplasmic activator may account for calcium accumulation in sickle cells."} {"id": "PMID:161858", "title": "Effect of oral contraceptive containing a new progestin (ORG 2969) on plasma renin activity, growth hormone and immunoreactive insulin.", "content": "Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle.", "contents": "Effect of oral contraceptive containing a new progestin (ORG 2969) on plasma renin activity, growth hormone and immunoreactive insulin. Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle."} {"id": "PMID:161861", "title": "The spontaneous rate of tumours in the laboratory rat: strain Chbb: THOM (SPF).", "content": "The aim of this investigation was to examine the time relationship of the rate of development of spontaneous tumours in the rat, strain CHBB: THOM (SPF). The rats were divided into 6 groups, each of which consisted of 100 male and 100 female animals. The first group was killed at the age of 15 months, and the last group when aged 2 1/2 years. Thus the time interval between sacrificing the individual groups was 3 months. Spontaneous tumours seldom appear in animals up to 15 months of age except in the testes, pituitary and mammary glands. Apart from these organs tumours develop mainly in the lung, lymph nodes, thymus, adrenal cortex, thyroid, ovary, uterus, skin and in the brain. Benign tumours predominate. Malignant tumours with metastases are rare. The incidence of tumour formation increases after the age 21 months. Statistically significant increases can only be shown in a few organs.", "contents": "The spontaneous rate of tumours in the laboratory rat: strain Chbb: THOM (SPF). The aim of this investigation was to examine the time relationship of the rate of development of spontaneous tumours in the rat, strain CHBB: THOM (SPF). The rats were divided into 6 groups, each of which consisted of 100 male and 100 female animals. The first group was killed at the age of 15 months, and the last group when aged 2 1/2 years. Thus the time interval between sacrificing the individual groups was 3 months. Spontaneous tumours seldom appear in animals up to 15 months of age except in the testes, pituitary and mammary glands. Apart from these organs tumours develop mainly in the lung, lymph nodes, thymus, adrenal cortex, thyroid, ovary, uterus, skin and in the brain. Benign tumours predominate. Malignant tumours with metastases are rare. The incidence of tumour formation increases after the age 21 months. Statistically significant increases can only be shown in a few organs."} {"id": "PMID:161862", "title": "[Interaction of phosphatidyl serine with fibrin monomer].", "content": "Phosphatidyl serine induces a concentration-dependent inhibition of polymerization of fibrin monomer and forms a complex with it, which is stable to gel-filtration and chloroform treatment. During plasmin proteolysis phosphatidyl serine remains tightly bound to the fragments of the fibrin monomer molecule formed. A correlation between the amount of amino acids responsible for phospholipid binding and that of phosphatidyl serine bound to the fragment of the fibrin monomer molecule was observed. The introduction of phosphatidyl serine into the blood flow causes a decrease of the thrombin-precipitated fibrinogen and fibrin monomer obtained from animal plasma. At the same time phosphatidyl serine is present in fibrinogen and in high amounts in the fibrin monomer. It is assumed that phosphatidyl serine which controls thrombinogenesis and enzymatic and non-enzymatic steps of fibrin production can thus be regarded as a natural stabilizer of the blood.", "contents": "[Interaction of phosphatidyl serine with fibrin monomer]. Phosphatidyl serine induces a concentration-dependent inhibition of polymerization of fibrin monomer and forms a complex with it, which is stable to gel-filtration and chloroform treatment. During plasmin proteolysis phosphatidyl serine remains tightly bound to the fragments of the fibrin monomer molecule formed. A correlation between the amount of amino acids responsible for phospholipid binding and that of phosphatidyl serine bound to the fragment of the fibrin monomer molecule was observed. The introduction of phosphatidyl serine into the blood flow causes a decrease of the thrombin-precipitated fibrinogen and fibrin monomer obtained from animal plasma. At the same time phosphatidyl serine is present in fibrinogen and in high amounts in the fibrin monomer. It is assumed that phosphatidyl serine which controls thrombinogenesis and enzymatic and non-enzymatic steps of fibrin production can thus be regarded as a natural stabilizer of the blood."} {"id": "PMID:161874", "title": "[Nil nocere: perforation of the gastric wall on occasion of peritoneoscopy (author's transl)].", "content": "On occasion of peritoneoscopy of a 76-years old man with gastrectasia by cancer of the pylorus, the gastric wall became perforated. He was cured by followed urgent surgical intervention. Causes and conclusions to prevent this complication are discussed.", "contents": "[Nil nocere: perforation of the gastric wall on occasion of peritoneoscopy (author's transl)]. On occasion of peritoneoscopy of a 76-years old man with gastrectasia by cancer of the pylorus, the gastric wall became perforated. He was cured by followed urgent surgical intervention. Causes and conclusions to prevent this complication are discussed."} {"id": "PMID:161875", "title": "The influence of experimental diabetes on the serum and urinary glycopeptide compounds in rats.", "content": "In alloxan-diabetic rats the protein level in the secomucoid and the levels of neutral sugars and peptides in the serum and urinary non-diffusible sugar-peptide (serum and urinary NSP) fractions increased. The proportion of neutral sugars in seromucoid and serum NSP fraction decreased, while in the urinary NSP fraction this ratio increased. In streptozotocin-diabetic rats the ratio of neutral sugars to the peptides did not change in either fraction, while the ratio of these sugars to the total nitrogen in the serum and urinary NSP fractions increased. The total level of seromucoid as well as the levels of neutral sugars in the serum and urinary NSP fraction were raised in these rats. The comparison of the results with those obtained previously by Sarnecka-Keller et al. (1968, 1972, 1972 a) in natural diabetes showed that the alloxan-diabetic model is more suitable for the study of glycopeptide compound metabolism in this disease.", "contents": "The influence of experimental diabetes on the serum and urinary glycopeptide compounds in rats. In alloxan-diabetic rats the protein level in the secomucoid and the levels of neutral sugars and peptides in the serum and urinary non-diffusible sugar-peptide (serum and urinary NSP) fractions increased. The proportion of neutral sugars in seromucoid and serum NSP fraction decreased, while in the urinary NSP fraction this ratio increased. In streptozotocin-diabetic rats the ratio of neutral sugars to the peptides did not change in either fraction, while the ratio of these sugars to the total nitrogen in the serum and urinary NSP fractions increased. The total level of seromucoid as well as the levels of neutral sugars in the serum and urinary NSP fraction were raised in these rats. The comparison of the results with those obtained previously by Sarnecka-Keller et al. (1968, 1972, 1972 a) in natural diabetes showed that the alloxan-diabetic model is more suitable for the study of glycopeptide compound metabolism in this disease."} {"id": "PMID:161876", "title": "[Autoradiographic studies on protein metabolism and histochemical demonstration of the brain zinc content in diabetes mellitus. 1. Comparison in experimental streptozotocin-induced diabetes].", "content": "By application of streptozotocin diabetes mellitus is induced in rats: 40 mg/kg body weight streptozotocin produce a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin cause a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals receive 8.33 mCi/animal 3H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3H-leucine in different areas of the rat brain are measured. The values of the control animals are compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3H-leucine values of the diabetic animals are considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3H-leucine values of diabetic animals decrease according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. Within the Ammon's horn and dentate fascia also the zinc contents change very specifically in different areas with the degree of severity of diabetes mellitus. The zinc is identified on H2S-alcohol fixed brains by means of a photographic development. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions is discussed.", "contents": "[Autoradiographic studies on protein metabolism and histochemical demonstration of the brain zinc content in diabetes mellitus. 1. Comparison in experimental streptozotocin-induced diabetes]. By application of streptozotocin diabetes mellitus is induced in rats: 40 mg/kg body weight streptozotocin produce a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin cause a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals receive 8.33 mCi/animal 3H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3H-leucine in different areas of the rat brain are measured. The values of the control animals are compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3H-leucine values of the diabetic animals are considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3H-leucine values of diabetic animals decrease according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. Within the Ammon's horn and dentate fascia also the zinc contents change very specifically in different areas with the degree of severity of diabetes mellitus. The zinc is identified on H2S-alcohol fixed brains by means of a photographic development. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions is discussed."} {"id": "PMID:161878", "title": "Medical geography of Moldavia: historical contribution.", "content": "The role of Hungarian surgeons and physicians in the medical care of Moldavia was discussed in its historical development. Two medico-geographical works about Moldavia in the first half of the 19th century were discussed: Andreas Wolff and the Moldavian Constantin Vernav wrote the related books.", "contents": "Medical geography of Moldavia: historical contribution. The role of Hungarian surgeons and physicians in the medical care of Moldavia was discussed in its historical development. Two medico-geographical works about Moldavia in the first half of the 19th century were discussed: Andreas Wolff and the Moldavian Constantin Vernav wrote the related books."} {"id": "PMID:161881", "title": "[Transluminal angioplasty of renal artery stenosis for the treatment of renal hypertension (author's transl)].", "content": "Three patients with hypertension due to renal artery stenoses were treated by percutaneous transluminal angioplasty with the coaxial-balloon-catheter system as it is used for the dilatation of coronary arteries. The pressure gradients before and after dilatation are recorded. Pressure of the three patients came directly after treatment down significantly. Reduction of antihypertensive drug therapy was possible in two patients, one patient is without therapy 4 weeks after the procedure.", "contents": "[Transluminal angioplasty of renal artery stenosis for the treatment of renal hypertension (author's transl)]. Three patients with hypertension due to renal artery stenoses were treated by percutaneous transluminal angioplasty with the coaxial-balloon-catheter system as it is used for the dilatation of coronary arteries. The pressure gradients before and after dilatation are recorded. Pressure of the three patients came directly after treatment down significantly. Reduction of antihypertensive drug therapy was possible in two patients, one patient is without therapy 4 weeks after the procedure."} {"id": "PMID:161882", "title": "[Delayed healing of colonic anastomoses after tumour resection (author's transl)].", "content": "Local tumour recurrences at colonic anastomoses in an early, curable stage are rarely missed by double contrast enema. On the other hand, the variable appearances caused by inflammatory lesions, which delay healing of the anastomosis, are often misinterpreted as recurrences. Early post-operative investigation with a water-soluble contrast medium is therefore important. Small and transient leaks at the suture line may cause intramural inflammatory lesions with a variety of symptoms and may be confused with local recurrences. They are due to delayed healing at the anastomosis and will only be interpreted correctly if there is regular radiological follow-up.", "contents": "[Delayed healing of colonic anastomoses after tumour resection (author's transl)]. Local tumour recurrences at colonic anastomoses in an early, curable stage are rarely missed by double contrast enema. On the other hand, the variable appearances caused by inflammatory lesions, which delay healing of the anastomosis, are often misinterpreted as recurrences. Early post-operative investigation with a water-soluble contrast medium is therefore important. Small and transient leaks at the suture line may cause intramural inflammatory lesions with a variety of symptoms and may be confused with local recurrences. They are due to delayed healing at the anastomosis and will only be interpreted correctly if there is regular radiological follow-up."} {"id": "PMID:161883", "title": "[Method and value of the opacified intestine in the computed tomography of abdomen (author's transl)].", "content": "In the examination of the intestine CT can deliver further information about diseases transgressing the intestinal wall or bordering on it. Sometimes, however, bowel loops filled with liquid can scarcely be distinguished from abdominal abnormalities. In these cases contrast material given orally or as an enema can facilitate the distinction and the identification of pathological patterns. The method of opacifying bowel loops is presented and demonstrated by several examples. Its value as well as its limits are discussed.", "contents": "[Method and value of the opacified intestine in the computed tomography of abdomen (author's transl)]. In the examination of the intestine CT can deliver further information about diseases transgressing the intestinal wall or bordering on it. Sometimes, however, bowel loops filled with liquid can scarcely be distinguished from abdominal abnormalities. In these cases contrast material given orally or as an enema can facilitate the distinction and the identification of pathological patterns. The method of opacifying bowel loops is presented and demonstrated by several examples. Its value as well as its limits are discussed."} {"id": "PMID:161884", "title": "[Critical considerations on the \"innominate grooves\" of the colon (author's transl)].", "content": "The authors discuss the meaning of the \"innominate grooves\" of the colon after having determined their anatomic substratum with a microradiographic study. In the iconographic and methodological critical evaluation of the double contrast technique the \"innominate grooves\" must be considered as an important sign of today's radiologic semeiotics and as elementary mucous structures which are first affected by pathologic situations.", "contents": "[Critical considerations on the \"innominate grooves\" of the colon (author's transl)]. The authors discuss the meaning of the \"innominate grooves\" of the colon after having determined their anatomic substratum with a microradiographic study. In the iconographic and methodological critical evaluation of the double contrast technique the \"innominate grooves\" must be considered as an important sign of today's radiologic semeiotics and as elementary mucous structures which are first affected by pathologic situations."} {"id": "PMID:161885", "title": "[99mTc marking of gel foam for catheter embolisation (author's transl)].", "content": "A simple method is described for marking gel foam particles with 99mTc after reduction of the pertechnetate. This is carried out in the Luer lock syringe to be used for the injection. After embolisation and control angiography, the patient is placed under a scintillation camera. The position of the embolising material can then be demonstrated scintigraphically. In six patients marked emboli were found to be correctly placed. In another patient undergoing a second embolisation for a renal tumour, particles were found in the peripheral circulation.", "contents": "[99mTc marking of gel foam for catheter embolisation (author's transl)]. A simple method is described for marking gel foam particles with 99mTc after reduction of the pertechnetate. This is carried out in the Luer lock syringe to be used for the injection. After embolisation and control angiography, the patient is placed under a scintillation camera. The position of the embolising material can then be demonstrated scintigraphically. In six patients marked emboli were found to be correctly placed. In another patient undergoing a second embolisation for a renal tumour, particles were found in the peripheral circulation."} {"id": "PMID:161886", "title": "[The value of renal phlebography in the differential diagnosis of arteriographically hypo- or avascular lesions in the kidney (author's transl)].", "content": "The present paper is an investigation into the diagnostic value of renal phlebography for differentiating between arteriographically hypo- and avascular malignant lesions in the kidney and benign renal masses. In three examinations carried out on eight patients with renal masses, phlebography was of crucial diagnostic importance. In ten renal cysts a presumptive diagnosis made by arteriography was confirmed by phlebography. In another eight renal cysts, a case of haemorrhagic pyelitis and in two cases of unilateral pseudotumerous pyelonephritis, phlebography was of no value.", "contents": "[The value of renal phlebography in the differential diagnosis of arteriographically hypo- or avascular lesions in the kidney (author's transl)]. The present paper is an investigation into the diagnostic value of renal phlebography for differentiating between arteriographically hypo- and avascular malignant lesions in the kidney and benign renal masses. In three examinations carried out on eight patients with renal masses, phlebography was of crucial diagnostic importance. In ten renal cysts a presumptive diagnosis made by arteriography was confirmed by phlebography. In another eight renal cysts, a case of haemorrhagic pyelitis and in two cases of unilateral pseudotumerous pyelonephritis, phlebography was of no value."} {"id": "PMID:161887", "title": "[Transhepatic biliary drainage for obstructive jaundice (author's transl)].", "content": "Sixty-five patients with obstructive jaundice out of a total of 71 patients, were treated successfully by PTCD. The markedly elevated total bilirubin and alkaline phosphatase in the serum were reduced significantly and the general condition of the patient improved rapidly. On the other hand, severe obstructive jaundice which had persisted for several weeks was not amenable to treatment in this way. Occlusion of the extrahepatic bile ducts by tumour was treated by internal PTCD; this provided satisfactory flow of bile into the duodenum for at least six months. PTCD is simpler for the patient than surgery and is therefore the method of choice in obstructive jaundice. Finally, PTCD can be used for the introduction of antibiotics for the treatment of suppurative cholangitis or liver abscesses. This rapidly leads to reduction in fever and absorption of the abscesses.", "contents": "[Transhepatic biliary drainage for obstructive jaundice (author's transl)]. Sixty-five patients with obstructive jaundice out of a total of 71 patients, were treated successfully by PTCD. The markedly elevated total bilirubin and alkaline phosphatase in the serum were reduced significantly and the general condition of the patient improved rapidly. On the other hand, severe obstructive jaundice which had persisted for several weeks was not amenable to treatment in this way. Occlusion of the extrahepatic bile ducts by tumour was treated by internal PTCD; this provided satisfactory flow of bile into the duodenum for at least six months. PTCD is simpler for the patient than surgery and is therefore the method of choice in obstructive jaundice. Finally, PTCD can be used for the introduction of antibiotics for the treatment of suppurative cholangitis or liver abscesses. This rapidly leads to reduction in fever and absorption of the abscesses."} {"id": "PMID:161888", "title": "[The Mirizzi syndrome as a cause of obstructive jaundice--its demonstration by sonography and PTC (author's transl)].", "content": "Two patients with the Mirizzi syndrome are described and the findings on sonography and PTC care discussed. The difficulties of differentiating this from biliary obstruction due to tumour are stressed and treatment and prognosis are set out.", "contents": "[The Mirizzi syndrome as a cause of obstructive jaundice--its demonstration by sonography and PTC (author's transl)]. Two patients with the Mirizzi syndrome are described and the findings on sonography and PTC care discussed. The difficulties of differentiating this from biliary obstruction due to tumour are stressed and treatment and prognosis are set out."} {"id": "PMID:161889", "title": "[Suggestibility as a factor in diagnostic decision-making, illustrated by lymphographic diagnosis (author's transl)].", "content": "Sixteen diagnosticians were repeatedly shown a series of lymphograms. On repeated viewing, the participants were informed of their diagnostic decisions at the first reading (accuracy, sensitivity, specificity). The results show that it was possible to influence the participants in their judgement and attitude. Changes in individual attitudes are demonstrated diagnostically and the individual diagnostic parameters were subjected to a quantitative analysis. The accuracy of the results are related to the method and to the diagnostician with reference to the composition of the clinical material.", "contents": "[Suggestibility as a factor in diagnostic decision-making, illustrated by lymphographic diagnosis (author's transl)]. Sixteen diagnosticians were repeatedly shown a series of lymphograms. On repeated viewing, the participants were informed of their diagnostic decisions at the first reading (accuracy, sensitivity, specificity). The results show that it was possible to influence the participants in their judgement and attitude. Changes in individual attitudes are demonstrated diagnostically and the individual diagnostic parameters were subjected to a quantitative analysis. The accuracy of the results are related to the method and to the diagnostician with reference to the composition of the clinical material."} {"id": "PMID:161890", "title": "[Long-term follow-up of stress injuries to the metaphyses and apophyses of the spinous processes of juvenile thoracic spines (Schmitt's disease) (author's transl)].", "content": "Unlike the clay-shoveller's fracture in adults, stress injuries in juveniles trend to be localised at the tip of the spinous process, i.e. in the metaphysis, the apophyseal line and the apophysis. Characteristic changes are found only between 14 1/2 and 16 1/2 years, at, or immediately before, ossification of the tip of the apophysis. These fractures share with the corresponding fractures in adults similar occupational history, a similar clinical picture with a benign course of the disease. Healing is by the formation of a pseudo-arthrosis which may, however, consolidate after several months or years. Synonyms which have been used for the stress injury to the spinous process in the growing skeleton are: clay-shoveller's fractures in juveniles, apophysitis of the spinous process, aseptic necrosis of the spinous process, gross disturbance of the spinous process after chronic trauma or Schmitt's disease.", "contents": "[Long-term follow-up of stress injuries to the metaphyses and apophyses of the spinous processes of juvenile thoracic spines (Schmitt's disease) (author's transl)]. Unlike the clay-shoveller's fracture in adults, stress injuries in juveniles trend to be localised at the tip of the spinous process, i.e. in the metaphysis, the apophyseal line and the apophysis. Characteristic changes are found only between 14 1/2 and 16 1/2 years, at, or immediately before, ossification of the tip of the apophysis. These fractures share with the corresponding fractures in adults similar occupational history, a similar clinical picture with a benign course of the disease. Healing is by the formation of a pseudo-arthrosis which may, however, consolidate after several months or years. Synonyms which have been used for the stress injury to the spinous process in the growing skeleton are: clay-shoveller's fractures in juveniles, apophysitis of the spinous process, aseptic necrosis of the spinous process, gross disturbance of the spinous process after chronic trauma or Schmitt's disease."} {"id": "PMID:161891", "title": "[Marginal osteophytes as a radiological and clinical indicator of patellofemoral arthrosis (author's transl)].", "content": "Radiological and pathological comparisons carried out on patellae at autopsy have shown a statistical relationship between the size of marginal patellar osteophytes and radiologically invisible ulceration of the joint cartilage. Patellar osteophytes greater than 2 mm. show a 100% association with cartilage ulcers. The detritus originating from the ulcerated cartilage is a potent irritant of the synovial membrane. The radiological demonstration of marginal patellar osteophytes therefore provides evidence concerning the severity of the arthrosis; the larger the patellar marginal osteophytes, the greater is the need for treatment of the painful arthrosis. The lateral and upper margins of the patella are the sites of predelection for the osteophytes. The medial patellar facet is the site of predelection for the cartilagenous ulcers.", "contents": "[Marginal osteophytes as a radiological and clinical indicator of patellofemoral arthrosis (author's transl)]. Radiological and pathological comparisons carried out on patellae at autopsy have shown a statistical relationship between the size of marginal patellar osteophytes and radiologically invisible ulceration of the joint cartilage. Patellar osteophytes greater than 2 mm. show a 100% association with cartilage ulcers. The detritus originating from the ulcerated cartilage is a potent irritant of the synovial membrane. The radiological demonstration of marginal patellar osteophytes therefore provides evidence concerning the severity of the arthrosis; the larger the patellar marginal osteophytes, the greater is the need for treatment of the painful arthrosis. The lateral and upper margins of the patella are the sites of predelection for the osteophytes. The medial patellar facet is the site of predelection for the cartilagenous ulcers."} {"id": "PMID:161892", "title": "[The appearances of chondropathia patellae on plain films (author's transl)].", "content": "The ability to diagnose chondropathia patellae on plain radiographs was studied in 64 patients in whom the disease had been confirmed either by operation or arthroscopy. All cases of stage III chondropathia were diagnosable by radiological examination; in stage I, 67%, and in stage II, 73% could be diagnosed. The diagnosis depends on the co-existence of marginal irregularities, irregularities of the subchondral bone lamellae, spotty diffuse demineralisation, marginal osteophytes, irregularities at the insertion of the quadriceps tendon and soft tissue changes such as joint effusions. These changes are best identified on the so-called \"defil\u00e9e\" view. Disalignment of the axis of the patella and post-traumatic defects are of particular importance for the development of chondropathia, but in the present clinical material, the existence of dysplasia of the patella or of the femoral condyle was not associated with a demonstrable increase of chondromalacia.", "contents": "[The appearances of chondropathia patellae on plain films (author's transl)]. The ability to diagnose chondropathia patellae on plain radiographs was studied in 64 patients in whom the disease had been confirmed either by operation or arthroscopy. All cases of stage III chondropathia were diagnosable by radiological examination; in stage I, 67%, and in stage II, 73% could be diagnosed. The diagnosis depends on the co-existence of marginal irregularities, irregularities of the subchondral bone lamellae, spotty diffuse demineralisation, marginal osteophytes, irregularities at the insertion of the quadriceps tendon and soft tissue changes such as joint effusions. These changes are best identified on the so-called \"defil\u00e9e\" view. Disalignment of the axis of the patella and post-traumatic defects are of particular importance for the development of chondropathia, but in the present clinical material, the existence of dysplasia of the patella or of the femoral condyle was not associated with a demonstrable increase of chondromalacia."} {"id": "PMID:161893", "title": "[Simplified multiscreen millimeter-layer ear-tomography-makeshift solution or more? (author's transl)].", "content": "The experiences of a simplified multiscreen millimeterlayer ear-tomography technique are reported. The number of patients examined 1969-1978 was 2000 and of these 730 were subjected to microsurgery. The accuracy of the tomographic method was evaluated by a correlation between the preoperative radiographic diagnoses and the peroperative findings. The diagnostic accuracy of multiscreen tomography was much better than expected. The advantages of the method are discussed. It is concluded that multiscreen millimeterlayer eartomography may profitably be used not only in larger departments but also in smaller units.", "contents": "[Simplified multiscreen millimeter-layer ear-tomography-makeshift solution or more? (author's transl)]. The experiences of a simplified multiscreen millimeterlayer ear-tomography technique are reported. The number of patients examined 1969-1978 was 2000 and of these 730 were subjected to microsurgery. The accuracy of the tomographic method was evaluated by a correlation between the preoperative radiographic diagnoses and the peroperative findings. The diagnostic accuracy of multiscreen tomography was much better than expected. The advantages of the method are discussed. It is concluded that multiscreen millimeterlayer eartomography may profitably be used not only in larger departments but also in smaller units."} {"id": "PMID:161894", "title": "[CT findings in brain abscesses (author's transl)].", "content": "Seventeen patients with brain abscesses are reported, some with multiple lesions. The computer tomographic criteria for the diagnosis with and without enhancement are described. The advantages of computer tomography compared with other neuroradiological methods for the diagnosis and follow-up of abscesses is stressed. Good therapeutic results have been obtained from simple puncture of the lesion.", "contents": "[CT findings in brain abscesses (author's transl)]. Seventeen patients with brain abscesses are reported, some with multiple lesions. The computer tomographic criteria for the diagnosis with and without enhancement are described. The advantages of computer tomography compared with other neuroradiological methods for the diagnosis and follow-up of abscesses is stressed. Good therapeutic results have been obtained from simple puncture of the lesion."} {"id": "PMID:161895", "title": "[Radiological documentation of the occurrence of occlusion of an internal carotid artery branch in a patient with hyperlipoproteinaemia (author's transl)].", "content": "The clinical and angiographic findings in a 23-year-old patient with hyperlipoproteinaemia type IV are described. The patient had suffered repeated, transitory attacks of focal cerebral ischaemia. During angiography, occlusion of a branch of the left middle cerebral artery occurred. This was followed by severe neurological deficit, which, however, recovered completely after three days. The pathogenesis of the angiographic findings and of this complication are discussed.", "contents": "[Radiological documentation of the occurrence of occlusion of an internal carotid artery branch in a patient with hyperlipoproteinaemia (author's transl)]. The clinical and angiographic findings in a 23-year-old patient with hyperlipoproteinaemia type IV are described. The patient had suffered repeated, transitory attacks of focal cerebral ischaemia. During angiography, occlusion of a branch of the left middle cerebral artery occurred. This was followed by severe neurological deficit, which, however, recovered completely after three days. The pathogenesis of the angiographic findings and of this complication are discussed."} {"id": "PMID:161896", "title": "[The effect of changes in the bones of the skull due to Mediterranean anaemia on the shape of the skull and the formation of the cranial cavity (author's transl)].", "content": "The head and skull in patients with Mediterraneen anaemia show often a marked change of the external shape due mainly to the considerable enlargement of the cranial bones. From the abnormal external appearance the suspicion may arise that the form and space of the internal cranial cavity are likewise affected and even the basic structure of the skull is altered. However, a detailed investigation of the principal angles, distances and characteristic structures of the skull made on lateral roentgenograms of these patients, a comparison of the results between cases with different intensity of the osseous changes and a confrontation with the findings in normal individuals proved that there were no major discrepancies. The essential features of the human skull were always preserved. Only in some cases with severe alterations of the cranial bones a few small deviations from the normal values could be noticed and in a little number of them signs of a slight narrowing of the cranial cavity werde to be observed. This way was probably caused by a very early, rapid and extreme enlargement of the cranial bones resulting in a kind of \"premature panzer-skull.\"", "contents": "[The effect of changes in the bones of the skull due to Mediterranean anaemia on the shape of the skull and the formation of the cranial cavity (author's transl)]. The head and skull in patients with Mediterraneen anaemia show often a marked change of the external shape due mainly to the considerable enlargement of the cranial bones. From the abnormal external appearance the suspicion may arise that the form and space of the internal cranial cavity are likewise affected and even the basic structure of the skull is altered. However, a detailed investigation of the principal angles, distances and characteristic structures of the skull made on lateral roentgenograms of these patients, a comparison of the results between cases with different intensity of the osseous changes and a confrontation with the findings in normal individuals proved that there were no major discrepancies. The essential features of the human skull were always preserved. Only in some cases with severe alterations of the cranial bones a few small deviations from the normal values could be noticed and in a little number of them signs of a slight narrowing of the cranial cavity werde to be observed. This way was probably caused by a very early, rapid and extreme enlargement of the cranial bones resulting in a kind of \"premature panzer-skull.\""} {"id": "PMID:161897", "title": "[The effect of selective autoperfusion through an extracorporeal circulation on the formation of arterial collaterals. Animal experimental results (author's transl)].", "content": "In 11 mongrel dogs (10-15 kg) with ligated superficial femoral arteries the formation of collaterals induced by increased arterial pressure with an extracorporal circulation was studied. In general anesthesia a teflon tube was inserted into one deep femoral artery. The other end of this tube war introduced through the right carotid artery into the thoracic aorta and arterial blood was drawn by a peristaltic tube pump from the aorta to the femoral artery. Different arterial pressures created by the pump were used to perfuse this hind limb. After 40 minutes perfusion time with 200 mmHG pressure, there was marked increase of collateralization by the deep femoral artery. At the contralateral non treated side, only minimal development of collaterals was visualized. These angiograms demonstrate that collaterals are opened by increased pressure within a short time interval The experimental model might have clinical implisations and accelerate collateral formation in non-surgical treatment of arterial occlusive disease.", "contents": "[The effect of selective autoperfusion through an extracorporeal circulation on the formation of arterial collaterals. Animal experimental results (author's transl)]. In 11 mongrel dogs (10-15 kg) with ligated superficial femoral arteries the formation of collaterals induced by increased arterial pressure with an extracorporal circulation was studied. In general anesthesia a teflon tube was inserted into one deep femoral artery. The other end of this tube war introduced through the right carotid artery into the thoracic aorta and arterial blood was drawn by a peristaltic tube pump from the aorta to the femoral artery. Different arterial pressures created by the pump were used to perfuse this hind limb. After 40 minutes perfusion time with 200 mmHG pressure, there was marked increase of collateralization by the deep femoral artery. At the contralateral non treated side, only minimal development of collaterals was visualized. These angiograms demonstrate that collaterals are opened by increased pressure within a short time interval The experimental model might have clinical implisations and accelerate collateral formation in non-surgical treatment of arterial occlusive disease."} {"id": "PMID:161910", "title": "Reinterpretation of the Dick test: role of group A streptococcal pyrogenic exotoxin.", "content": "Because of the association of the group A streptococcal pyrogenic exotoxins (SPEs) with erythrogenic toxin used in the classical Dick test, the involvement of the SPEs in production of erythematous skin reactions was assessed. Unless they had been presensitized, young adult rabbits failed to show skin reactions after intracutaneous challenged with SPEs. Rabbits presensitized to purified protein derivative exhibited enhanced skin reactivity when given purified protein derivative plus SPE C; the enhancement was neutralized by antiserum to SPE C. Rabbits sensitized to bovine serum albumin showed extensive red rash development resembling scarlet fever rashes when given bovine serum albumin containing SPE C. Desquamation occurred 5 to 10 days after injection. Animals sensitized to one SPE type showed enhanced skin reactivity to challenge with homologous or heterologous SPE types, indicating the presence of a cross-reactive determinant within the SPE molecules. Repeated challenge of SPE-sensitized animals with homologous toxin resulted in concomitant antitoxin production with reduction of the enhanced skin reactivities, until typical delayed-hypersensitivity skin reactions remained. The data indicate that, in addition to the toxic reaction previously described, SPEs enhance Arthus and delayed-hypersensitivity skin reactions. It follows that erythrogenic toxin represents the enhancement of acquired skin reactivity to streptococcal antigens by one or more SPE types. Therefore, the Dick test measures SPE-enhanced hypersensitivity to streptococcal products.", "contents": "Reinterpretation of the Dick test: role of group A streptococcal pyrogenic exotoxin. Because of the association of the group A streptococcal pyrogenic exotoxins (SPEs) with erythrogenic toxin used in the classical Dick test, the involvement of the SPEs in production of erythematous skin reactions was assessed. Unless they had been presensitized, young adult rabbits failed to show skin reactions after intracutaneous challenged with SPEs. Rabbits presensitized to purified protein derivative exhibited enhanced skin reactivity when given purified protein derivative plus SPE C; the enhancement was neutralized by antiserum to SPE C. Rabbits sensitized to bovine serum albumin showed extensive red rash development resembling scarlet fever rashes when given bovine serum albumin containing SPE C. Desquamation occurred 5 to 10 days after injection. Animals sensitized to one SPE type showed enhanced skin reactivity to challenge with homologous or heterologous SPE types, indicating the presence of a cross-reactive determinant within the SPE molecules. Repeated challenge of SPE-sensitized animals with homologous toxin resulted in concomitant antitoxin production with reduction of the enhanced skin reactivities, until typical delayed-hypersensitivity skin reactions remained. The data indicate that, in addition to the toxic reaction previously described, SPEs enhance Arthus and delayed-hypersensitivity skin reactions. It follows that erythrogenic toxin represents the enhancement of acquired skin reactivity to streptococcal antigens by one or more SPE types. Therefore, the Dick test measures SPE-enhanced hypersensitivity to streptococcal products."} {"id": "PMID:161911", "title": "Biological activity of the slime and endotoxin of the periodontopathic organism Eikenella corrodens.", "content": "A partially purified water-soluble slime extract was obtained from two strains of the oral pathogen Eikenella corrodens, designated CS10 A and CS10 B. Endotoxin was also isolated from this organism by the phenol-water extraction procedure. Assays including the local Shwartzman skin reactivity, chicken embryo lethality, Limulus lysate clotting, spleen cell mitogenicity, and immune adjuvancy were used to test the biological properties of these two bacterial extracts. In each of these assay systems the endotoxins of the Eikenella corrodens strains demonstrated the classical endotoxic responses. In contrast, the effect of slime extract in the corresponding assays was either extremely low or absent with the exception of a very strong immunosuppressive effect. Mice treated with slime extract showed a severely reduced immune response to sheep erythrocytes as measured by the hemolytic plaque-forming cell assay.", "contents": "Biological activity of the slime and endotoxin of the periodontopathic organism Eikenella corrodens. A partially purified water-soluble slime extract was obtained from two strains of the oral pathogen Eikenella corrodens, designated CS10 A and CS10 B. Endotoxin was also isolated from this organism by the phenol-water extraction procedure. Assays including the local Shwartzman skin reactivity, chicken embryo lethality, Limulus lysate clotting, spleen cell mitogenicity, and immune adjuvancy were used to test the biological properties of these two bacterial extracts. In each of these assay systems the endotoxins of the Eikenella corrodens strains demonstrated the classical endotoxic responses. In contrast, the effect of slime extract in the corresponding assays was either extremely low or absent with the exception of a very strong immunosuppressive effect. Mice treated with slime extract showed a severely reduced immune response to sheep erythrocytes as measured by the hemolytic plaque-forming cell assay."} {"id": "PMID:161920", "title": "[Plastic replacement of the abdominal wall by uncoated carbon cloth. An animal experiment on the rabbit (author's transl)].", "content": "Carbon cloth is a new biomaterial which is suitable for the replacement of ligaments and connective tissues, because of its biological and physical properties. In 30 rabbits a defect was cut into the abdominal wall. In 20 the defect was covered by an implanted carbon cloth. The other 10 animals were used as controls. After implantation wound healing was excellent. No herniation could be observed in the group with the implants. After 3 months histological examinations revealed the ingrowth of collagen fibres into the carbon cloth. It had become a strong and resilient abdominal wall replacement. A physical-strength test showed stability of the newly formed abdominal wall with good anchorage to normal tissue.", "contents": "[Plastic replacement of the abdominal wall by uncoated carbon cloth. An animal experiment on the rabbit (author's transl)]. Carbon cloth is a new biomaterial which is suitable for the replacement of ligaments and connective tissues, because of its biological and physical properties. In 30 rabbits a defect was cut into the abdominal wall. In 20 the defect was covered by an implanted carbon cloth. The other 10 animals were used as controls. After implantation wound healing was excellent. No herniation could be observed in the group with the implants. After 3 months histological examinations revealed the ingrowth of collagen fibres into the carbon cloth. It had become a strong and resilient abdominal wall replacement. A physical-strength test showed stability of the newly formed abdominal wall with good anchorage to normal tissue."} {"id": "PMID:161922", "title": "[Evidence for receptors of the specific T-suppressor cells immune to the H-2 antigens, and enrichment of these cells by fractionation on target cell monolayer].", "content": "Specific T-suppressor cells induced by an intravenous injection of mice with a large number of gamma-irradiated allogeneic spleen cells are shown to inhibit the DNA synthesis activation and the killer generation in mixed lymphocyte culture (MLC). These suppressors can be removed from the population as a result of their adherence to the macrophage monolayer of the corresponding donor strain, whereas only a small part of specific suppresors gets adherent to the syngeneic macrophage monolayer. Subsequent elution of the lymphocytes adherent to the specific monolayer gives rise to the enrichment of the cell population in specific T-suppressors by a factor of 30 and 2.6, judging by the reduction of lymphocyte number required for 50% inhibition of the DNA synthesis and the killer generation, respectively. The gain in suppressor activity appears to be specific, as it is not observed when either the elution is performed from the syngeneic monolayer, or the third-party stimulator cells are used in the test-MLC. The faint non-specific suppression of the reactions to thirdparty stimulator cells in the test-MCL which intact immune lymphocytes are responsible for, does not decrease after their absorption but almost disappears after their elution from the specific monolayer. The findings are indicative of the existence of antigen-binding receptors on T-suppressors which allow to remove and concentrate specific T-suppressor cells.", "contents": "[Evidence for receptors of the specific T-suppressor cells immune to the H-2 antigens, and enrichment of these cells by fractionation on target cell monolayer]. Specific T-suppressor cells induced by an intravenous injection of mice with a large number of gamma-irradiated allogeneic spleen cells are shown to inhibit the DNA synthesis activation and the killer generation in mixed lymphocyte culture (MLC). These suppressors can be removed from the population as a result of their adherence to the macrophage monolayer of the corresponding donor strain, whereas only a small part of specific suppresors gets adherent to the syngeneic macrophage monolayer. Subsequent elution of the lymphocytes adherent to the specific monolayer gives rise to the enrichment of the cell population in specific T-suppressors by a factor of 30 and 2.6, judging by the reduction of lymphocyte number required for 50% inhibition of the DNA synthesis and the killer generation, respectively. The gain in suppressor activity appears to be specific, as it is not observed when either the elution is performed from the syngeneic monolayer, or the third-party stimulator cells are used in the test-MLC. The faint non-specific suppression of the reactions to thirdparty stimulator cells in the test-MCL which intact immune lymphocytes are responsible for, does not decrease after their absorption but almost disappears after their elution from the specific monolayer. The findings are indicative of the existence of antigen-binding receptors on T-suppressors which allow to remove and concentrate specific T-suppressor cells."} {"id": "PMID:161933", "title": "Sex-related differences in the response of fast and slow muscle fibres to early undernutrition.", "content": "Early undernutrition of male and female rats was effected by limiting the mothers' food supply by 40% during pregnancy and lactation. The rats were killed at the age of 20 weeks and physiologically fast and slow skeletal muscles were prepared for histochemical demonstration of muscle fibre types. In the fast extensor digitorum longus (EDL) and the slow soleus (SOL) significant decreases in muscle weight were seen only in male experimental animals. Decreases in muscle fibre type cross-sectional area were found in the EDL in both males and females. In SOL, both fibre types showed evidence of fibre hypertrophy, and this was statistically significant in male animals. No changes were seen in the proportions present of the fibre types in either of the muscles.", "contents": "Sex-related differences in the response of fast and slow muscle fibres to early undernutrition. Early undernutrition of male and female rats was effected by limiting the mothers' food supply by 40% during pregnancy and lactation. The rats were killed at the age of 20 weeks and physiologically fast and slow skeletal muscles were prepared for histochemical demonstration of muscle fibre types. In the fast extensor digitorum longus (EDL) and the slow soleus (SOL) significant decreases in muscle weight were seen only in male experimental animals. Decreases in muscle fibre type cross-sectional area were found in the EDL in both males and females. In SOL, both fibre types showed evidence of fibre hypertrophy, and this was statistically significant in male animals. No changes were seen in the proportions present of the fibre types in either of the muscles."} {"id": "PMID:161935", "title": "Toxicity of oxythioquinox in relation to the fat content of the diet: study of the metabolic activity of rat intestinal epithelium.", "content": "The relationship between the level of lipid calories in the diet and the effects of oxythioquinox, administered for 30 days at 200 mg/kg fresh food, was studied on the metabolism of enterocytes. The results show that the QO2, the QG and the QL of the enterocytes drop both, with the level of lipid intake and with the presence of oxythioquinox. The (Na+ + K+) ATPase, Mg+ +ATPase and arylamidase activities of a homogenate of enterocytes all increase both with the level of alimentary lipids and with the presence of oxythioquinox, the effect of oxythioquinox being potentialized by the lipids. Alkaline phosphatase was found to be the only enzyme to be inhibited in the treated animals and the lipid-oxythioquinox interaction moves in the direction of a decrease in this inhibition. For most of the investigated parameters, because of the interaction, as the level of lipid calories increases, the toxicity of oxythioquinox becomes noticeably modified.", "contents": "Toxicity of oxythioquinox in relation to the fat content of the diet: study of the metabolic activity of rat intestinal epithelium. The relationship between the level of lipid calories in the diet and the effects of oxythioquinox, administered for 30 days at 200 mg/kg fresh food, was studied on the metabolism of enterocytes. The results show that the QO2, the QG and the QL of the enterocytes drop both, with the level of lipid intake and with the presence of oxythioquinox. The (Na+ + K+) ATPase, Mg+ +ATPase and arylamidase activities of a homogenate of enterocytes all increase both with the level of alimentary lipids and with the presence of oxythioquinox, the effect of oxythioquinox being potentialized by the lipids. Alkaline phosphatase was found to be the only enzyme to be inhibited in the treated animals and the lipid-oxythioquinox interaction moves in the direction of a decrease in this inhibition. For most of the investigated parameters, because of the interaction, as the level of lipid calories increases, the toxicity of oxythioquinox becomes noticeably modified."} {"id": "PMID:161942", "title": "[Prenatal diagnosis by ultrasound of a very large heart (author's transl)].", "content": "Ultrasound diagnosis enabled identification of a congenitally very large heart. Due to this finding, no obstetric intervention was performed despite a foetal emergency situation. Hence, unnecessary surgery was avoided. The principal signs enabling clarification of the case by ultrasound were a vena umbilicalis of 2 cm thickness and the highly dilated heart which occupied 75% of the cross-sectional area of the thorax, besides the clinical clues, hydramnion and hydrops fetus.", "contents": "[Prenatal diagnosis by ultrasound of a very large heart (author's transl)]. Ultrasound diagnosis enabled identification of a congenitally very large heart. Due to this finding, no obstetric intervention was performed despite a foetal emergency situation. Hence, unnecessary surgery was avoided. The principal signs enabling clarification of the case by ultrasound were a vena umbilicalis of 2 cm thickness and the highly dilated heart which occupied 75% of the cross-sectional area of the thorax, besides the clinical clues, hydramnion and hydrops fetus."} {"id": "PMID:161946", "title": "[Hemodynamic guidelines in the treatment of acute myocardial infarction by means of vasodilators].", "content": "Two types of vasodilators are used for treatment of acute myocardial infarction: Nitrates on the one hand with predominant venodilation and agents like Phentolamie and Nitroprusside on the other hand with venodilation as well as arteriolar vasodilation. Different opinions exist with respect to indication of these vasodilators. They are used for reduction of arterial blood pressure, for reduction of left ventricular filling pressure and for increase of cardiac output. A marked decrease in ejection fraction is the hemodynamic basis of application of vasodilators in the latter indication. By reduction of peripheral vascular resistance emptying of the left ventricle in these patients is enhanced.) As a working hypothesis in clinical situation elevated filling pressure indicates a decreased ejection fraction. The first part of this investigation deals with relation of left ventricular and diastolic pressure to ejection fraction. A good correlation between these two parameters was found in 717 patients with coronary artery disease. However variability was so wide that regression from enddiastolic pressure to ejection fraction in the individual seemed impossible. In 26.6% of patients with ejection fraction over 0.6%, filling pressure was 20 mm Hg or more. On the other hand, in 34.7% of patients with ejection fraction below 0.3% filling pressure was 20 mm Hg or less. As a consequence of practical value, reduced ejection fraction has to be assumed, if a patient presents elevated filling pressure and reduced cardiac output. In the second part, the hemodynamic effects of Phentolamine in 12 patients with acute myocardial infarction and elevated filling pressure (PCV resp. PADP greater than 18 mm Hg) are described. Maximal effects on hemodynamic variables were: reduction of peripheral vascular resistance by 31.4%, of left ventricular filling pressure by 16.2%, and of mean arterial pressure by 17.0%. Cardiac output increased by 25.8% and heart rate rose by 14.8%. At optimal efficacy, stroke volume increased by 23.7%. Further increase of infusion rate with concomitant fall of peripheral vascular resistance resulted in decrease of stroke volume and tachycardia. Most serious side effects consisted in sudden fall of blood pressure. Therefore intraarterial monitoring of blood pressure is demanded. The third part deals with hemodynamic effects of nitrates (Isosorbiddinitrate 10 mg p.o.) in patients with acute myocardial infarction and elevated filling pressure. One hour after application peripheral vascular resistance decrease by 16.5%, filling pressure by 20.8%, and mean arterial pressure by 9.0%. Cardiac output stroke volume and heart rate did not change significantly. No side effects were observed with Isosorbiddinitrate although two cases of nitrate syncope occurred with Nitroglycerin, resulting in bradycardia and hypotension. Indications for vasodilator therapy therefore has to be handled as follows: Nitrates should be given to patients with elevated filling pressure and normal cardiac output...", "contents": "[Hemodynamic guidelines in the treatment of acute myocardial infarction by means of vasodilators]. Two types of vasodilators are used for treatment of acute myocardial infarction: Nitrates on the one hand with predominant venodilation and agents like Phentolamie and Nitroprusside on the other hand with venodilation as well as arteriolar vasodilation. Different opinions exist with respect to indication of these vasodilators. They are used for reduction of arterial blood pressure, for reduction of left ventricular filling pressure and for increase of cardiac output. A marked decrease in ejection fraction is the hemodynamic basis of application of vasodilators in the latter indication. By reduction of peripheral vascular resistance emptying of the left ventricle in these patients is enhanced.) As a working hypothesis in clinical situation elevated filling pressure indicates a decreased ejection fraction. The first part of this investigation deals with relation of left ventricular and diastolic pressure to ejection fraction. A good correlation between these two parameters was found in 717 patients with coronary artery disease. However variability was so wide that regression from enddiastolic pressure to ejection fraction in the individual seemed impossible. In 26.6% of patients with ejection fraction over 0.6%, filling pressure was 20 mm Hg or more. On the other hand, in 34.7% of patients with ejection fraction below 0.3% filling pressure was 20 mm Hg or less. As a consequence of practical value, reduced ejection fraction has to be assumed, if a patient presents elevated filling pressure and reduced cardiac output. In the second part, the hemodynamic effects of Phentolamine in 12 patients with acute myocardial infarction and elevated filling pressure (PCV resp. PADP greater than 18 mm Hg) are described. Maximal effects on hemodynamic variables were: reduction of peripheral vascular resistance by 31.4%, of left ventricular filling pressure by 16.2%, and of mean arterial pressure by 17.0%. Cardiac output increased by 25.8% and heart rate rose by 14.8%. At optimal efficacy, stroke volume increased by 23.7%. Further increase of infusion rate with concomitant fall of peripheral vascular resistance resulted in decrease of stroke volume and tachycardia. Most serious side effects consisted in sudden fall of blood pressure. Therefore intraarterial monitoring of blood pressure is demanded. The third part deals with hemodynamic effects of nitrates (Isosorbiddinitrate 10 mg p.o.) in patients with acute myocardial infarction and elevated filling pressure. One hour after application peripheral vascular resistance decrease by 16.5%, filling pressure by 20.8%, and mean arterial pressure by 9.0%. Cardiac output stroke volume and heart rate did not change significantly. No side effects were observed with Isosorbiddinitrate although two cases of nitrate syncope occurred with Nitroglycerin, resulting in bradycardia and hypotension. Indications for vasodilator therapy therefore has to be handled as follows: Nitrates should be given to patients with elevated filling pressure and normal cardiac output..."} {"id": "PMID:161947", "title": "Suppressor cell induction and reticuloendothelial cells activation produced in the mouse by beta 1-3 glucan.", "content": "We made a sequential study of the proliferative and functional changes occurring in RE cells after beta 1-3 glucan administration in BDF1, and C57BL mouse. beta 1-3 glucan was administered by single i.v. 50 mg/kg or i.p. 15 mg/kg injection. This successively induced changes in RE cells as follows: on day 3 a rise of acid phosphatase activity in peritoneal macrophages; on day 6 an increase of 3H-TdR incorporation in spleen and peritoneal lymphocytes together with an intense suppression of PHA and LPS responses by spleen cells; on day 10 a 5-fold increase of the percentage of peroxidase rich monocytes in the peritoneum. Thereafter all the values went back to or below control. Our results indicate that beta 1-3 glucan is an in vivo mitogen and a macrophage activator.", "contents": "Suppressor cell induction and reticuloendothelial cells activation produced in the mouse by beta 1-3 glucan. We made a sequential study of the proliferative and functional changes occurring in RE cells after beta 1-3 glucan administration in BDF1, and C57BL mouse. beta 1-3 glucan was administered by single i.v. 50 mg/kg or i.p. 15 mg/kg injection. This successively induced changes in RE cells as follows: on day 3 a rise of acid phosphatase activity in peritoneal macrophages; on day 6 an increase of 3H-TdR incorporation in spleen and peritoneal lymphocytes together with an intense suppression of PHA and LPS responses by spleen cells; on day 10 a 5-fold increase of the percentage of peroxidase rich monocytes in the peritoneum. Thereafter all the values went back to or below control. Our results indicate that beta 1-3 glucan is an in vivo mitogen and a macrophage activator."} {"id": "PMID:161948", "title": "[Investigation of house-dust allergy in children (author's transl)].", "content": "Authors were studying the relationship between the history data, the diagnostic difficulties, the skin tests and ventilatory functions after provocative inhalation and specific IgE positivity in connection with 40 cases of bronchial asthma. The most important feature of the treatment is the specific hyposensibilisation, which was performed by a depot house-dust preparation, manufactured by the Vaccine Producing Institute \"Human\", Budapest. Full success was given in 61,1% of the treated asthmatics.", "contents": "[Investigation of house-dust allergy in children (author's transl)]. Authors were studying the relationship between the history data, the diagnostic difficulties, the skin tests and ventilatory functions after provocative inhalation and specific IgE positivity in connection with 40 cases of bronchial asthma. The most important feature of the treatment is the specific hyposensibilisation, which was performed by a depot house-dust preparation, manufactured by the Vaccine Producing Institute \"Human\", Budapest. Full success was given in 61,1% of the treated asthmatics."} {"id": "PMID:161949", "title": "[Intracutaneous tests with phytohemagglutinin for detection of cell-mediated immunity (author's transl)].", "content": "Patients with various forms of dermatosis and healthy control subjects were simultaneously tested intracutaneously with specific antigens (candidin, trichophytin, kabikinase, tuberculin and the mumps skin test antigen) and the non-specificmitogen PHA-P. A positive delayed reaction was observed in 98% of the healthy subjects and 76,6% of the dermatosis patients following intracutaneous application of 2 microgram PHA-P.--The results of these studies suggest that the PHA-P intracutaneous test might be suitable as a screening method for diagnozing cellular immun-defects.", "contents": "[Intracutaneous tests with phytohemagglutinin for detection of cell-mediated immunity (author's transl)]. Patients with various forms of dermatosis and healthy control subjects were simultaneously tested intracutaneously with specific antigens (candidin, trichophytin, kabikinase, tuberculin and the mumps skin test antigen) and the non-specificmitogen PHA-P. A positive delayed reaction was observed in 98% of the healthy subjects and 76,6% of the dermatosis patients following intracutaneous application of 2 microgram PHA-P.--The results of these studies suggest that the PHA-P intracutaneous test might be suitable as a screening method for diagnozing cellular immun-defects."} {"id": "PMID:161950", "title": "[On the suitability of migration inhibition techniques in the in-vitro-diagnostics of chromium allergy (author's transl)].", "content": "1. Under the conditions of cell culture potassium dichromate is reduced to trivalent chromium (diphenylcarbacid/fotometry). Trivalent chromium reacts with proteins more strongly than the hexavalent chromium (gelchromatography/atom absorption spectrophotometry) and presumably represents the actual hapten. 2. Because of this in-vitro-conjugation chromium salts are suitable in their unconjugated form for applying in migration inhibition tests (capillary/Clausen technique). 3. In migration inhibition tests potassium dichromate showed a better antigenicity than chromium chloride. The capillary method was more sensitive than the Clausen technique when using the same test concentration. 4. Correlations between the degree of the patch test and the value of the migration inhibition did not exist.", "contents": "[On the suitability of migration inhibition techniques in the in-vitro-diagnostics of chromium allergy (author's transl)]. 1. Under the conditions of cell culture potassium dichromate is reduced to trivalent chromium (diphenylcarbacid/fotometry). Trivalent chromium reacts with proteins more strongly than the hexavalent chromium (gelchromatography/atom absorption spectrophotometry) and presumably represents the actual hapten. 2. Because of this in-vitro-conjugation chromium salts are suitable in their unconjugated form for applying in migration inhibition tests (capillary/Clausen technique). 3. In migration inhibition tests potassium dichromate showed a better antigenicity than chromium chloride. The capillary method was more sensitive than the Clausen technique when using the same test concentration. 4. Correlations between the degree of the patch test and the value of the migration inhibition did not exist."} {"id": "PMID:161951", "title": "[Acute keratoconus in mongolism (author s transl)].", "content": "Ten cases of mongolism are reported in which acute keratoconus developed. The results according to age and sex distribution, onset of the disease, status of the fellow eye, and histology of the cornea are compared with former reports. Our theory of the etiopathogenesis of acute keratoconus in patients with trisomy 21 and other diseases with generalized weakness of the connective tissue is presented and discussed.", "contents": "[Acute keratoconus in mongolism (author s transl)]. Ten cases of mongolism are reported in which acute keratoconus developed. The results according to age and sex distribution, onset of the disease, status of the fellow eye, and histology of the cornea are compared with former reports. Our theory of the etiopathogenesis of acute keratoconus in patients with trisomy 21 and other diseases with generalized weakness of the connective tissue is presented and discussed."} {"id": "PMID:161952", "title": "An investigation of seven enzymes as possible genetic markers in horse leucocytes.", "content": "In this paper we describe seven enzymes, NP, GOTM, PGM2, alpha FUC, PEP A, ADA and MPI which are found in the white cells of horses, including 39 British crossbred ponies and 16 crossbred horses, 30 Mongolian ponies and 10 Icelandic ponies. Two of these enzymes--alpha FUC and MPI--were polymorphic in all the populations of horses studied and could prove useful as additional markers in the paternity testing of horses. PEP A and GOTM were also polymorphic in two of the populations studied and could be used as further markers in these populations.", "contents": "An investigation of seven enzymes as possible genetic markers in horse leucocytes. In this paper we describe seven enzymes, NP, GOTM, PGM2, alpha FUC, PEP A, ADA and MPI which are found in the white cells of horses, including 39 British crossbred ponies and 16 crossbred horses, 30 Mongolian ponies and 10 Icelandic ponies. Two of these enzymes--alpha FUC and MPI--were polymorphic in all the populations of horses studied and could prove useful as additional markers in the paternity testing of horses. PEP A and GOTM were also polymorphic in two of the populations studied and could be used as further markers in these populations."} {"id": "PMID:161953", "title": "Geographical variation of lactate dehydrogenase and phosphoglucomutase in the loach Misgurnus anguillicaudatus.", "content": "One of the two loci controlling muscle lactate dehydrogenase (LDH) was shown to be polymorphic in the loach Misgurnus anguillicaudatus. The result of the survey on four populations suggests that the differences in the LDH gene frequencies are correlated with the geographical distribution of the loach. A fourth phosphoglucomutase allele (PGMD) was found in one of the loach populations examined.", "contents": "Geographical variation of lactate dehydrogenase and phosphoglucomutase in the loach Misgurnus anguillicaudatus. One of the two loci controlling muscle lactate dehydrogenase (LDH) was shown to be polymorphic in the loach Misgurnus anguillicaudatus. The result of the survey on four populations suggests that the differences in the LDH gene frequencies are correlated with the geographical distribution of the loach. A fourth phosphoglucomutase allele (PGMD) was found in one of the loach populations examined."} {"id": "PMID:161955", "title": "[Pachydermatoglyphy. A sign of malignancy for acanthosis nigricans (author's transl)].", "content": "The pachydermatoglyphy corresponds from the clinical point of view to a diffuse palmo-plantar keratodermia, of a yellowish color, characterised by a rough thickening of the finger prints. The presence of the pachydermatoglyphy has been pointed out in six cases of malignant acanthosis nigricans. This was already found in previous descriptions. Pachydermatoglyphy is specially found in malignant acanthosis nigricans, but we have also observed such cases in erythrokeratodermia with pilar keratosis and deafness.", "contents": "[Pachydermatoglyphy. A sign of malignancy for acanthosis nigricans (author's transl)]. The pachydermatoglyphy corresponds from the clinical point of view to a diffuse palmo-plantar keratodermia, of a yellowish color, characterised by a rough thickening of the finger prints. The presence of the pachydermatoglyphy has been pointed out in six cases of malignant acanthosis nigricans. This was already found in previous descriptions. Pachydermatoglyphy is specially found in malignant acanthosis nigricans, but we have also observed such cases in erythrokeratodermia with pilar keratosis and deafness."} {"id": "PMID:161956", "title": "[Fusarium graminearum in silages. Zearalenone production (author's transl)].", "content": "Zearalenone natural contamination of transverse sections of recently opened silages has been observed. In our in vitro experiments, there is no zearalenone production on corn by Fusarium graminearum in anaerobic jar during 3 months. However, on confined atmosphere, zearalenone production is 1.5 to 3 ppm. Contamination of silage is not possible if there are anaerobic conditions in silages.", "contents": "[Fusarium graminearum in silages. Zearalenone production (author's transl)]. Zearalenone natural contamination of transverse sections of recently opened silages has been observed. In our in vitro experiments, there is no zearalenone production on corn by Fusarium graminearum in anaerobic jar during 3 months. However, on confined atmosphere, zearalenone production is 1.5 to 3 ppm. Contamination of silage is not possible if there are anaerobic conditions in silages."} {"id": "PMID:161958", "title": "[In vitro studies of testicular biosynthesis in 4 cases of male pseudohermaphrodism (MPH) due to testicular 17 ketoreductase defect (author's transl)].", "content": "In 3 cases of MPH due to 17-ketosteroid reductase defect, the pattern of testicular biosynthesis studied after incubating homogenates of testicular tissue with 14C-Progesterone and 3H-Pregnenolone was very similar. The most striking finding was the excessive production of delta 4-Androstenedione contrasting with the small amount of testosterone formed. Conversion of DHA to delta 5-Androstenediol was also limited. In addition, 3 pairs of substrates, namely 14C-testosterone and 3H-delta 4-androstenedione; 14C-estradiol and 3H-estrone; 14C-delta 5-androstenediol and 3H-DHA, were incubated for various length of time. Homogenates of testicular tissue from 2 cases presenting with the biosynthetic defect were studied as to compare to testicular tissues from 2 subjects with normal testicular biosynthesis. Different degrees in the impairment of the reduction or the oxydation were observed for the different pairs of substrates in pathological as well as in normal tissues. This suggests that the extent of the enzyme defect would differ for the 3 pairs of substrates.", "contents": "[In vitro studies of testicular biosynthesis in 4 cases of male pseudohermaphrodism (MPH) due to testicular 17 ketoreductase defect (author's transl)]. In 3 cases of MPH due to 17-ketosteroid reductase defect, the pattern of testicular biosynthesis studied after incubating homogenates of testicular tissue with 14C-Progesterone and 3H-Pregnenolone was very similar. The most striking finding was the excessive production of delta 4-Androstenedione contrasting with the small amount of testosterone formed. Conversion of DHA to delta 5-Androstenediol was also limited. In addition, 3 pairs of substrates, namely 14C-testosterone and 3H-delta 4-androstenedione; 14C-estradiol and 3H-estrone; 14C-delta 5-androstenediol and 3H-DHA, were incubated for various length of time. Homogenates of testicular tissue from 2 cases presenting with the biosynthetic defect were studied as to compare to testicular tissues from 2 subjects with normal testicular biosynthesis. Different degrees in the impairment of the reduction or the oxydation were observed for the different pairs of substrates in pathological as well as in normal tissues. This suggests that the extent of the enzyme defect would differ for the 3 pairs of substrates."} {"id": "PMID:161967", "title": "Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro.", "content": "In vitro lymphoproliferative responses to foreign histocompatibility antigens are phylogenetically restricted. Responses occur most readily to allogeneic or closely related xenogeneic leucocytes, but not to unrelated xenogeneic cells. Specific cytotoxic T cell responses to foreign histocompatibility antigens show the same phylogenetic restriction. This lack of xenoreactivity is not due to a lack of precursor cells for the xenoantigens; guinea-pig lymphocytes, although normally unresponsive to mouse antigens, have a similar precursor frequency for these antigens as do lymphocytes of allogeneic mouse strains. Specific cytotoxic responses of guinea-pig lymphocytes to mouse antigens can be generated if a factor released from con A stimulated guinea-pig spleen cells is added to the culture medium. The factor produced by con A-activated spleen cells (CS) is also phylogenetically restricted in its action; CS must be obtained from animals homologous with the donor of the responding lymphocytes.", "contents": "Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro. In vitro lymphoproliferative responses to foreign histocompatibility antigens are phylogenetically restricted. Responses occur most readily to allogeneic or closely related xenogeneic leucocytes, but not to unrelated xenogeneic cells. Specific cytotoxic T cell responses to foreign histocompatibility antigens show the same phylogenetic restriction. This lack of xenoreactivity is not due to a lack of precursor cells for the xenoantigens; guinea-pig lymphocytes, although normally unresponsive to mouse antigens, have a similar precursor frequency for these antigens as do lymphocytes of allogeneic mouse strains. Specific cytotoxic responses of guinea-pig lymphocytes to mouse antigens can be generated if a factor released from con A stimulated guinea-pig spleen cells is added to the culture medium. The factor produced by con A-activated spleen cells (CS) is also phylogenetically restricted in its action; CS must be obtained from animals homologous with the donor of the responding lymphocytes."} {"id": "PMID:161974", "title": "[DNA sequence encoding the signal peptide of the lambda receptor in E. coli K 12].", "content": "A 181 base pairs DNA fragment from E. coli K 12 has been sequenced. This allows determination of the sequence of the signal peptide of the precursor for the lambda receptor, an outer membrane protein.", "contents": "[DNA sequence encoding the signal peptide of the lambda receptor in E. coli K 12]. A 181 base pairs DNA fragment from E. coli K 12 has been sequenced. This allows determination of the sequence of the signal peptide of the precursor for the lambda receptor, an outer membrane protein."} {"id": "PMID:161976", "title": "[Reconstruction of abdominal wall defects using corium. Surgical procedure, clinical results and manometric examination of postoperative abdominal wall function].", "content": "Extensive resection of the abdominal wall was performed on six patients to reconstruct defects caused by tumors or necroses. Autologous dermis covered by a flap plasty produced good clinical and functional results, documented by the measurement of intraabdominal pressures in response to coughing, pressing, and lifting of the legs. The autologous dermis graft represents a valuable tool for the closure of large defects of the abdominal wall.", "contents": "[Reconstruction of abdominal wall defects using corium. Surgical procedure, clinical results and manometric examination of postoperative abdominal wall function]. Extensive resection of the abdominal wall was performed on six patients to reconstruct defects caused by tumors or necroses. Autologous dermis covered by a flap plasty produced good clinical and functional results, documented by the measurement of intraabdominal pressures in response to coughing, pressing, and lifting of the legs. The autologous dermis graft represents a valuable tool for the closure of large defects of the abdominal wall."} {"id": "PMID:161979", "title": "Nonelectrophoretic genetic variability in mosquitoes: polymorphism for temperature-resistant and temperature-sensitive phosphoglucomutase alleles in Culex pipiens.", "content": "Homogenates of single individuals of two natural populations and five laboratory populations of Culex pipiens were examined by combining electrophoresis and heat denaturation studies on phosphoglucomutase (PGM). All populations showed a high degree of polymorphism for isoelectrophoretic temperature-resistant (tr) and temperature-sensitive (ts) alleles. Formal genetic data on the heat stability differences of the PGM are given. If both electrophoretic and isoelectrophoretic alleles are taken into account, the mean increase in the degree of heterozygosity is quite remarkable, i.e., about 65%.--The data are considered in relation to the biological significance that this new type of variability of structural genes could have in natural populations.", "contents": "Nonelectrophoretic genetic variability in mosquitoes: polymorphism for temperature-resistant and temperature-sensitive phosphoglucomutase alleles in Culex pipiens. Homogenates of single individuals of two natural populations and five laboratory populations of Culex pipiens were examined by combining electrophoresis and heat denaturation studies on phosphoglucomutase (PGM). All populations showed a high degree of polymorphism for isoelectrophoretic temperature-resistant (tr) and temperature-sensitive (ts) alleles. Formal genetic data on the heat stability differences of the PGM are given. If both electrophoretic and isoelectrophoretic alleles are taken into account, the mean increase in the degree of heterozygosity is quite remarkable, i.e., about 65%.--The data are considered in relation to the biological significance that this new type of variability of structural genes could have in natural populations."} {"id": "PMID:161983", "title": "[The indications for laparoscopy in malignant tumours of the ovary (author's transl)].", "content": "The diagnosis of a malignant ovarian tumour can be made laparoscopically. It is particularly indicated in cases of ascites occurring by itself due to a neoplasm or of undiagnosed origin, and in cases of infiltration of the pelvic nodes or when a small abdominal mass, whether it is isolated or associated with ascites, is found. This particularly of value when a cytological examination of the ascitic fluid does not indicate the diagnosis. Laparoscopy is a means by which the degree of spread of abdomino-pelvic lesions can be discerned in cases where the malignant nature of the ovary is known, but where the prognoses for its removal, either immediately or after several cures with chemotherapy, are doubtful and where the degree of spread has not been correctly and precisely determined at the first surgical intervention. Therefore laparoscopy can complete the information obtained from pelvic examinations and avoid the need for carrying out an exploratory laparotomy, but is gives less information than this latter does about the degree of spread in the pelvis and in the abdomen. So, laparoscopy is a means by which repeated control of the results of therapy which is more thorough than clinical examination can be assured, particularly because it acts as a check on peritoneal cytology. Although its interpretation can be very difficult and its reliability is a relative one, the latter is a good criterion of follow-up.", "contents": "[The indications for laparoscopy in malignant tumours of the ovary (author's transl)]. The diagnosis of a malignant ovarian tumour can be made laparoscopically. It is particularly indicated in cases of ascites occurring by itself due to a neoplasm or of undiagnosed origin, and in cases of infiltration of the pelvic nodes or when a small abdominal mass, whether it is isolated or associated with ascites, is found. This particularly of value when a cytological examination of the ascitic fluid does not indicate the diagnosis. Laparoscopy is a means by which the degree of spread of abdomino-pelvic lesions can be discerned in cases where the malignant nature of the ovary is known, but where the prognoses for its removal, either immediately or after several cures with chemotherapy, are doubtful and where the degree of spread has not been correctly and precisely determined at the first surgical intervention. Therefore laparoscopy can complete the information obtained from pelvic examinations and avoid the need for carrying out an exploratory laparotomy, but is gives less information than this latter does about the degree of spread in the pelvis and in the abdomen. So, laparoscopy is a means by which repeated control of the results of therapy which is more thorough than clinical examination can be assured, particularly because it acts as a check on peritoneal cytology. Although its interpretation can be very difficult and its reliability is a relative one, the latter is a good criterion of follow-up."} {"id": "PMID:161984", "title": "[Prevention of recurring adhesions after tuboplasty. II. Importance of grafts with free pezitoneum (author's transl)].", "content": "We have greatly improved in prevention of adhesions after tuboplasty, using peritoneal grafts on crude surfaces (28 cases off 92 tuboplasties). First results seem to confirm the interest of this method.", "contents": "[Prevention of recurring adhesions after tuboplasty. II. Importance of grafts with free pezitoneum (author's transl)]. We have greatly improved in prevention of adhesions after tuboplasty, using peritoneal grafts on crude surfaces (28 cases off 92 tuboplasties). First results seem to confirm the interest of this method."} {"id": "PMID:161991", "title": "A review of work on artificial tendons.", "content": "Work done to date on artificial tendons by many authors is described in chronological order. A brief description of the techniques and materials is given in each case, with a summary of the results. The overall implications of the work are discussed in terms of prosthesis durability, the attachment to bone and tendon, mechanical properties and the volume of scar tissue generated. It is concluded that construction of a permanent artificial tendon is a realistic and worthwhile aim; further experimental work ought to include long term in vivo testing with means provided for monitoring any drift of the attachment points.", "contents": "A review of work on artificial tendons. Work done to date on artificial tendons by many authors is described in chronological order. A brief description of the techniques and materials is given in each case, with a summary of the results. The overall implications of the work are discussed in terms of prosthesis durability, the attachment to bone and tendon, mechanical properties and the volume of scar tissue generated. It is concluded that construction of a permanent artificial tendon is a realistic and worthwhile aim; further experimental work ought to include long term in vivo testing with means provided for monitoring any drift of the attachment points."} {"id": "PMID:161992", "title": "A comparison of palantype and stenograph for use in a speech transcription aid for the deaf.", "content": "In spite of considerable reasearch over many years in the field of automatic speech recognition (Underwood, 1977), practical devices capable of recognising unrestricted speech remain as science fiction rather than fact. Simultaneous display of speech as an aid for the deaf has however, been accomplished using manual data input devices (Newell and King, 1977; Newell, 1978; Downton and Newell; Fox et al, 1975; Hayward, 1978). In this application shorthand typing machines have been used, because only they can keep pace with speech (Seibel, 1964). Two possible machines are currently available for English Transcriptions; the Palantype (a British device) and the Stenograph (an American device). They are both based on the same fundamental principles, but differ mechanically and in the typing conventions they use. These differences suggest that one machine may be superior to the other as an input device for an aid for the deaf. This paper compares the two shorthand systems with a view to their potential use in a system providing a simultaneous transcript of speech for the deaf.", "contents": "A comparison of palantype and stenograph for use in a speech transcription aid for the deaf. In spite of considerable reasearch over many years in the field of automatic speech recognition (Underwood, 1977), practical devices capable of recognising unrestricted speech remain as science fiction rather than fact. Simultaneous display of speech as an aid for the deaf has however, been accomplished using manual data input devices (Newell and King, 1977; Newell, 1978; Downton and Newell; Fox et al, 1975; Hayward, 1978). In this application shorthand typing machines have been used, because only they can keep pace with speech (Seibel, 1964). Two possible machines are currently available for English Transcriptions; the Palantype (a British device) and the Stenograph (an American device). They are both based on the same fundamental principles, but differ mechanically and in the typing conventions they use. These differences suggest that one machine may be superior to the other as an input device for an aid for the deaf. This paper compares the two shorthand systems with a view to their potential use in a system providing a simultaneous transcript of speech for the deaf."} {"id": "PMID:161993", "title": "A high-affinity ATP-binding site on 30S dynein.", "content": "The enhancing effect of low concentrations (eg, 8 microM) of bis(4-fluoro-3-nitrophenyl)sulfone (FNS) on 30S dynein ATPase activity is increased when 1 mM dithiothreitol (DTT) is present. The effect of FNS + DTT is optimal at pH 7.5. Activation of the latent ATPase activity of 30S dynein by FNS + DTT is partially prevented by 1--3 microM ATP. Adenylylimidodiphosphate (AMP-PNP) is less effective than ATP, while beta, gamma-methylene-adenosine triphosphase (AMP-PCP), though a much stronger inhibitor of ATPase activity than AMP-PNP, does not protect against enhancement. These results demonstrate the presence of high-affinity ATP-binding site on 30S dynein.", "contents": "A high-affinity ATP-binding site on 30S dynein. The enhancing effect of low concentrations (eg, 8 microM) of bis(4-fluoro-3-nitrophenyl)sulfone (FNS) on 30S dynein ATPase activity is increased when 1 mM dithiothreitol (DTT) is present. The effect of FNS + DTT is optimal at pH 7.5. Activation of the latent ATPase activity of 30S dynein by FNS + DTT is partially prevented by 1--3 microM ATP. Adenylylimidodiphosphate (AMP-PNP) is less effective than ATP, while beta, gamma-methylene-adenosine triphosphase (AMP-PCP), though a much stronger inhibitor of ATPase activity than AMP-PNP, does not protect against enhancement. These results demonstrate the presence of high-affinity ATP-binding site on 30S dynein."} {"id": "PMID:161997", "title": "[2 cases of substitution of the portal vein with a dacron prosthesis during pancreatectomy for carcinoma of the head of the pancreas].", "content": "The Authors report their experience concerning two cases of pancreatic carcinoma in which growth involvement of retropancreatic venous peduncle required the removal of a tract 6 and 8 cm long of the mesenteric-portal axis and its replacement with knitted dacron graft. The first patient died 8 months later due to massive pulmonar and hepatic metastases. The second patient died in the early post-operative course due to septic shock and dacron graft did not show any evidence of lumen obstruction at post-mortem examination. In spite of the lack of controlled clinical trials which provide a well defined method of staging for carcinoma of the pancreas, the authors' experience shows the possibility of extending radical resections also to cases which usually are considered unresectable and in absence of politetrafluoroethylene graft also with the use of interposed knitted dacron graft good results can be achieved.", "contents": "[2 cases of substitution of the portal vein with a dacron prosthesis during pancreatectomy for carcinoma of the head of the pancreas]. The Authors report their experience concerning two cases of pancreatic carcinoma in which growth involvement of retropancreatic venous peduncle required the removal of a tract 6 and 8 cm long of the mesenteric-portal axis and its replacement with knitted dacron graft. The first patient died 8 months later due to massive pulmonar and hepatic metastases. The second patient died in the early post-operative course due to septic shock and dacron graft did not show any evidence of lumen obstruction at post-mortem examination. In spite of the lack of controlled clinical trials which provide a well defined method of staging for carcinoma of the pancreas, the authors' experience shows the possibility of extending radical resections also to cases which usually are considered unresectable and in absence of politetrafluoroethylene graft also with the use of interposed knitted dacron graft good results can be achieved."} {"id": "PMID:162002", "title": "Angiocardiographic and haemodynamic studies in chronic haemodialysis patients with cardiomegaly.", "content": "Twenty-one chronic haemodialysis patients with cardiomegaly and repeated episodes of heart failure were selected for left ventricular cineangiography and haemodynamic studies. Left ventricular end-diastolic (LVED) volume was augmented in eleven, LVED pressure increased in fourteen, and ejection fraction decreased in nine patients. A decrease of maximum velocity of myocardial fibre shortening was observed in fifteen, and of normalised ventricular rigidity index in eleven. Many patients had diminished cardiac performance in the absence of demonstrable coronary heart disease, hypertension, or chronic volume overload. The diagnosis of congestive cardiomyopathy of unknown aetiology, possibly related to uraemia, was reached in ten patients.", "contents": "Angiocardiographic and haemodynamic studies in chronic haemodialysis patients with cardiomegaly. Twenty-one chronic haemodialysis patients with cardiomegaly and repeated episodes of heart failure were selected for left ventricular cineangiography and haemodynamic studies. Left ventricular end-diastolic (LVED) volume was augmented in eleven, LVED pressure increased in fourteen, and ejection fraction decreased in nine patients. A decrease of maximum velocity of myocardial fibre shortening was observed in fifteen, and of normalised ventricular rigidity index in eleven. Many patients had diminished cardiac performance in the absence of demonstrable coronary heart disease, hypertension, or chronic volume overload. The diagnosis of congestive cardiomyopathy of unknown aetiology, possibly related to uraemia, was reached in ten patients."} {"id": "PMID:162003", "title": "Detection of memory cells by chemical modification of the lymphocyte cell surface.", "content": "Stringent alloantigen requirements, necessary for the differentiation of human memory cells into specific secondary cytolytic T cells (2 degrees CTL), can be bypassed by chemical modification of memory cells with the mitogenic oxidising agent, galactose oxidase. Treatment of memory cells generated in a long-term primary mixed lymphocyte culture with neuraminidase and galactose oxidase (NAGO) results in the differentiation of memory cells into 2 degrees CTL. In contrast, treatment of unprimed cells with NAGO does not result in CTL production despite the proliferation resulting from such treatment.", "contents": "Detection of memory cells by chemical modification of the lymphocyte cell surface. Stringent alloantigen requirements, necessary for the differentiation of human memory cells into specific secondary cytolytic T cells (2 degrees CTL), can be bypassed by chemical modification of memory cells with the mitogenic oxidising agent, galactose oxidase. Treatment of memory cells generated in a long-term primary mixed lymphocyte culture with neuraminidase and galactose oxidase (NAGO) results in the differentiation of memory cells into 2 degrees CTL. In contrast, treatment of unprimed cells with NAGO does not result in CTL production despite the proliferation resulting from such treatment."} {"id": "PMID:162004", "title": "Donor specific suppressor cells in association with rejection of a renal allograft.", "content": "Details are presented of three aspects of immunological monitoring in a single instance of severe irreversible rejection of a renal allograft. Rejection is associated with strong evidence of lymphocyte mediated cytotoxicity (LMC). During this period reduced responsiveness of recipient cells to stimulation in vitro by donor cells is observed; this is more reduced than is responsiveness to random cells. Donor-specific suppressor cells also develop, as detected in two systems. It is postulated that the data are evidence that competition exists between different agressive and suppressive subpopulation of recipient lymphocytes.", "contents": "Donor specific suppressor cells in association with rejection of a renal allograft. Details are presented of three aspects of immunological monitoring in a single instance of severe irreversible rejection of a renal allograft. Rejection is associated with strong evidence of lymphocyte mediated cytotoxicity (LMC). During this period reduced responsiveness of recipient cells to stimulation in vitro by donor cells is observed; this is more reduced than is responsiveness to random cells. Donor-specific suppressor cells also develop, as detected in two systems. It is postulated that the data are evidence that competition exists between different agressive and suppressive subpopulation of recipient lymphocytes."} {"id": "PMID:162005", "title": "Plasma exchange in immune complex disease.", "content": "The effect of plasma exchange on CIC, anti-dsDNA and complement levels and clinical activity was studied in eight patients with SLE, one with idiopathic anaphylactoid purpura and one with mixed cryoglobulinaemia. No association existed between different tests for immune complex detection. Plasma exchange as sole therapy was effective in patients with idiopathic anaphylactoid purpura and mixed cryoglobulinaemia, but not in one SLE patient with CIC. Five SLE patients with CIC treated with corticosteroids showed improvement on plasma exchange but in two patients with and two with CIC plasma exchange was not effective.", "contents": "Plasma exchange in immune complex disease. The effect of plasma exchange on CIC, anti-dsDNA and complement levels and clinical activity was studied in eight patients with SLE, one with idiopathic anaphylactoid purpura and one with mixed cryoglobulinaemia. No association existed between different tests for immune complex detection. Plasma exchange as sole therapy was effective in patients with idiopathic anaphylactoid purpura and mixed cryoglobulinaemia, but not in one SLE patient with CIC. Five SLE patients with CIC treated with corticosteroids showed improvement on plasma exchange but in two patients with and two with CIC plasma exchange was not effective."} {"id": "PMID:162006", "title": "Pathogenetic role of mesangial immune deposits.", "content": "This investigation was designed to clarify the pathogenetic role of immune complexes within the mesangium. We administered a ferritin-protein antigen to rats which localised and persisted within the mesangium. Subsequently administration of anti-ferritin antibody resulted in binding of antibody to the mesangially located antigen. The effect of this immune complex formed in situ was studied in long-term experiments and no evidence of glomerular impairment was seen. These results lend support to the view that an immunological process, confined to the mesangium, may not necessarily compromise renal function.", "contents": "Pathogenetic role of mesangial immune deposits. This investigation was designed to clarify the pathogenetic role of immune complexes within the mesangium. We administered a ferritin-protein antigen to rats which localised and persisted within the mesangium. Subsequently administration of anti-ferritin antibody resulted in binding of antibody to the mesangially located antigen. The effect of this immune complex formed in situ was studied in long-term experiments and no evidence of glomerular impairment was seen. These results lend support to the view that an immunological process, confined to the mesangium, may not necessarily compromise renal function."} {"id": "PMID:162016", "title": "[Pathomorphological changes in the estrogenic syndrome of swine].", "content": "Epizootic, clinical and pathomorphological investigations were carried out on spontaneously arising oestrogen syndrome in swine following feeding with fodder mixture containing 35-63% maize in which the oestrogen substance z-2 (zearalenon) was found. Clinical symptoms and pathomorphological changes observed in the course of the disease are described. Varying in extent edematous processes were present in the regions around the anus, vulva, prepucium and the mammal complex. Uteruses were twice or thrice enlarged. Varying in size (pea grain to pigeon egg) cystose formations, sclerotic and atrophic changes were found in the ovaries of swine, which had suffered from vulvo-edema and were slaughtered after three months because they could not come in heat. Degenerative changes of the parenchymal organs, blood vessel disturbances in the uterine wall and various degenerative, atrophic and cystose changes in the ovarian folicules were histologically observed.", "contents": "[Pathomorphological changes in the estrogenic syndrome of swine]. Epizootic, clinical and pathomorphological investigations were carried out on spontaneously arising oestrogen syndrome in swine following feeding with fodder mixture containing 35-63% maize in which the oestrogen substance z-2 (zearalenon) was found. Clinical symptoms and pathomorphological changes observed in the course of the disease are described. Varying in extent edematous processes were present in the regions around the anus, vulva, prepucium and the mammal complex. Uteruses were twice or thrice enlarged. Varying in size (pea grain to pigeon egg) cystose formations, sclerotic and atrophic changes were found in the ovaries of swine, which had suffered from vulvo-edema and were slaughtered after three months because they could not come in heat. Degenerative changes of the parenchymal organs, blood vessel disturbances in the uterine wall and various degenerative, atrophic and cystose changes in the ovarian folicules were histologically observed."} {"id": "PMID:162017", "title": "[The determination, secretion and plasma concentration of androgens].", "content": "The present state of modern methods for the determination and some data for secretion and plasma levels of the principal circulating androgens (testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, androstenedione and dehydroepiandrosterone) in men and women under normal and pathological conditions are described.", "contents": "[The determination, secretion and plasma concentration of androgens]. The present state of modern methods for the determination and some data for secretion and plasma levels of the principal circulating androgens (testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, androstenedione and dehydroepiandrosterone) in men and women under normal and pathological conditions are described."} {"id": "PMID:162018", "title": "[Determination of flow capacity in valves for ventriculo-auricular drainage].", "content": "In model experiments both of the customary valves for ventriculo-auricular draining (Spitz-Holter valve and Pudenz-Heyer valve) are tried. Aperient pressures as well as flow amounts in relation to given pressure values are determined and plotted. In long-term examination for 1 year both kinds of valves exhibit irregular flow capacities, that have no significant tendency in the Spitz-Holter valve, whereas the flow through the Pudenz-Heyer valve is more and more diminished during the course of time.", "contents": "[Determination of flow capacity in valves for ventriculo-auricular drainage]. In model experiments both of the customary valves for ventriculo-auricular draining (Spitz-Holter valve and Pudenz-Heyer valve) are tried. Aperient pressures as well as flow amounts in relation to given pressure values are determined and plotted. In long-term examination for 1 year both kinds of valves exhibit irregular flow capacities, that have no significant tendency in the Spitz-Holter valve, whereas the flow through the Pudenz-Heyer valve is more and more diminished during the course of time."} {"id": "PMID:162020", "title": "Histoenzymatic changes in the dog kidney in an experimentally induced crushing injury of the thorax.", "content": "The experiments were carried out on dogs. Experimental animals were subjected to the trauma of the thorax during operation. The localization and activity of succinic dehydrogenase, NADH2-tetrazole reductase, adenosine triphosphatase, alkaline and acid phosphates in the kidneys were examined. An increase of the activity of all the investigated enzymes takes place under the influence of the stress. On the basis of the investigations it can be supposed that the processes of oxygen phosphorylation and active transport are intensified. An increase of the activity of acid phosphates gives evidence of the intensity of phagocytosis and pinocytosis processes in the kidney.", "contents": "Histoenzymatic changes in the dog kidney in an experimentally induced crushing injury of the thorax. The experiments were carried out on dogs. Experimental animals were subjected to the trauma of the thorax during operation. The localization and activity of succinic dehydrogenase, NADH2-tetrazole reductase, adenosine triphosphatase, alkaline and acid phosphates in the kidneys were examined. An increase of the activity of all the investigated enzymes takes place under the influence of the stress. On the basis of the investigations it can be supposed that the processes of oxygen phosphorylation and active transport are intensified. An increase of the activity of acid phosphates gives evidence of the intensity of phagocytosis and pinocytosis processes in the kidney."} {"id": "PMID:162011", "title": "[Bronchiectasis and definitive assisted ventilation (author's transl)].", "content": "A 39 year old female with severe respiratory insufficiency by bronchiectasis is treated by assisted ventilation at home. Indication is discussed.", "contents": "[Bronchiectasis and definitive assisted ventilation (author's transl)]. A 39 year old female with severe respiratory insufficiency by bronchiectasis is treated by assisted ventilation at home. Indication is discussed."} {"id": "PMID:162021", "title": "[Late results of patients with amputation of the thigh (author's transl)].", "content": "111 patients with amputation of the thigh of the last world war were examined. Besides the complaints in their thigh they suffered mostly from low back pain and osteoarthritis in the knee of the other leg. For a medical report it is important to decide whether the low back pain comes from lumbar disc disease or from secondary scoliosis of the lumbar spine which is caused by the amputation. Secondary changes in the spine and in the other leg can also be expected when a lower limb is heavily injured.", "contents": "[Late results of patients with amputation of the thigh (author's transl)]. 111 patients with amputation of the thigh of the last world war were examined. Besides the complaints in their thigh they suffered mostly from low back pain and osteoarthritis in the knee of the other leg. For a medical report it is important to decide whether the low back pain comes from lumbar disc disease or from secondary scoliosis of the lumbar spine which is caused by the amputation. Secondary changes in the spine and in the other leg can also be expected when a lower limb is heavily injured."} {"id": "PMID:162024", "title": "Effect of in vivo and in vitro application of glucagon, insulin and epinephrine on Ca++-transport properties of liver mitochondria.", "content": "In vivo administration of glucagon, insulin or epinephrine, respectively, gives rise to an increase of Ca++-retention time as well as of the Ca++-uptake rate in subsequently isolated rat liver mitochondria. Whereas the changes of Ca++-transport properties after pretreatment with glucagon or epinephrine occur already 6--15 min after their administration, the effect of insulin is observed not earlier than 30 min after its application. Under diabetic and starving conditions the Ca++-retention time of isolated liver mitochondria is prolonged, whereas no alteration of the uptake rate occurs. Since alloxan as well as streptozotocin induced qualitatively similar changes, a specific action of alloxan on liver mitochondria can be ruled out. Application of insulin 60--90 min prior to decapitation normalizes the changes of mitochondrial Ca++-transport observed under chronic alloxan diabetic conditions. Cycloheximide abolishes the prolongation of Ca++-retention in mitochondria from alloxan diabetic rats, but has no influence on the changes induced by glucagon pretreatment.", "contents": "Effect of in vivo and in vitro application of glucagon, insulin and epinephrine on Ca++-transport properties of liver mitochondria. In vivo administration of glucagon, insulin or epinephrine, respectively, gives rise to an increase of Ca++-retention time as well as of the Ca++-uptake rate in subsequently isolated rat liver mitochondria. Whereas the changes of Ca++-transport properties after pretreatment with glucagon or epinephrine occur already 6--15 min after their administration, the effect of insulin is observed not earlier than 30 min after its application. Under diabetic and starving conditions the Ca++-retention time of isolated liver mitochondria is prolonged, whereas no alteration of the uptake rate occurs. Since alloxan as well as streptozotocin induced qualitatively similar changes, a specific action of alloxan on liver mitochondria can be ruled out. Application of insulin 60--90 min prior to decapitation normalizes the changes of mitochondrial Ca++-transport observed under chronic alloxan diabetic conditions. Cycloheximide abolishes the prolongation of Ca++-retention in mitochondria from alloxan diabetic rats, but has no influence on the changes induced by glucagon pretreatment."} {"id": "PMID:162025", "title": "Competition between extramitochondrial and intramitochondrial ATP-consuming processes.", "content": "The relationship between intra- and extramitochondrial ATP utilization was investigated in liver mitochondria isolated from normally fed, starved and high-protein fed rats. ATP export was provoked by adding a hexokinase-glucose-trap and intramitochondrial ATP consumption by adding ammonia, bicarbonate and ornithine in order to stimulate citrulline synthesis. Both processes compete for ATP produced via oxidative phosphorylation; the rate of citrulline formation declines as the extramitochondrial [ATP]/[ADP] ratio decreases. It is concluded that ATP for adenine nucleotide translocation and that for carbamoyl phosphate synthesis are delivered from a common intramitochondrial pool of adenine nucleotides. In mitochondria from rats with a high-protein diet, citrulline synthesis greatly stimulates the rate of oxidative phosphorylation (about two thirds of state 3 respiration). Under these conditions the intramitochondrial [ATP]/[ADP] ratio is significantly reduced. The intramitochondrial [ATP]/[ADP] ratio is not in thermodynamic equilibrium with the extramitochondrial one.", "contents": "Competition between extramitochondrial and intramitochondrial ATP-consuming processes. The relationship between intra- and extramitochondrial ATP utilization was investigated in liver mitochondria isolated from normally fed, starved and high-protein fed rats. ATP export was provoked by adding a hexokinase-glucose-trap and intramitochondrial ATP consumption by adding ammonia, bicarbonate and ornithine in order to stimulate citrulline synthesis. Both processes compete for ATP produced via oxidative phosphorylation; the rate of citrulline formation declines as the extramitochondrial [ATP]/[ADP] ratio decreases. It is concluded that ATP for adenine nucleotide translocation and that for carbamoyl phosphate synthesis are delivered from a common intramitochondrial pool of adenine nucleotides. In mitochondria from rats with a high-protein diet, citrulline synthesis greatly stimulates the rate of oxidative phosphorylation (about two thirds of state 3 respiration). Under these conditions the intramitochondrial [ATP]/[ADP] ratio is significantly reduced. The intramitochondrial [ATP]/[ADP] ratio is not in thermodynamic equilibrium with the extramitochondrial one."} {"id": "PMID:162026", "title": "Muscle spindles in the human anterior digastric muscle.", "content": "The occurrence of muscle spindles in the anterior digastric muscle in man was investigated and the fibre calibre spectrum of the corresponding nerve was determined. After removal at autopsy from five individuals of both sexes (aged 23--73), the muscles were stained with Weigert's iron hematoxylin-van Gieson stain and the nerves according to the Alzheimer - Mann - H\u00e4ggqvist method. Altogether 12 spindles were found in five out of ten muscles. Only muscles from one individual were devoid of spindles. This sparsity or absence was supported by analyses of fibre calibre spectra. The small number of spindles and the fact that they do not occur in all muscles or in all individuals, suggest that they are not an essential source of sensory information.", "contents": "Muscle spindles in the human anterior digastric muscle. The occurrence of muscle spindles in the anterior digastric muscle in man was investigated and the fibre calibre spectrum of the corresponding nerve was determined. After removal at autopsy from five individuals of both sexes (aged 23--73), the muscles were stained with Weigert's iron hematoxylin-van Gieson stain and the nerves according to the Alzheimer - Mann - H\u00e4ggqvist method. Altogether 12 spindles were found in five out of ten muscles. Only muscles from one individual were devoid of spindles. This sparsity or absence was supported by analyses of fibre calibre spectra. The small number of spindles and the fact that they do not occur in all muscles or in all individuals, suggest that they are not an essential source of sensory information."} {"id": "PMID:162027", "title": "[The influence of climatic treatment on the levels of complement and some lysosomal enzymes in serum of patients with asthma bronchiale (author's transl)].", "content": "It was found that the levels of CH50, C3, complement component. lysozyme, beta-D-glucuronidase, and acid phosphatase were increased in blood serum of patients with asthma bronchiale during a climatic treatment in the highmountain condition of Strbsk\u00e9 Pleso (altitude 1,350 m). The increase of CH50 was monophasic, while the changes of other factors were biphasic--increasing at the beginning and falling down to the starting values at the end of the treatment. The changes observed are a part of the adaptation of organism to the high-mountain condition.", "contents": "[The influence of climatic treatment on the levels of complement and some lysosomal enzymes in serum of patients with asthma bronchiale (author's transl)]. It was found that the levels of CH50, C3, complement component. lysozyme, beta-D-glucuronidase, and acid phosphatase were increased in blood serum of patients with asthma bronchiale during a climatic treatment in the highmountain condition of Strbsk\u00e9 Pleso (altitude 1,350 m). The increase of CH50 was monophasic, while the changes of other factors were biphasic--increasing at the beginning and falling down to the starting values at the end of the treatment. The changes observed are a part of the adaptation of organism to the high-mountain condition."} {"id": "PMID:162028", "title": "[Cross reaction of specific IgE antibodies directed against cow's milk and bovine hair (author's transl)].", "content": "Sera of 25 children living in town were examined by means of RAST on the presence of IgE antibody against milk and cow's hair antigens. 18 cases had IgE antibodies reacting with milk and 9 with cow's hair. There was correlation between the levels of these antibodies with the exception of two cases. The results give evidence that half of the asthmatic children allergic to milk will react with bronchospasm in the cases if they ar exposed to inhalation of cow's hair.", "contents": "[Cross reaction of specific IgE antibodies directed against cow's milk and bovine hair (author's transl)]. Sera of 25 children living in town were examined by means of RAST on the presence of IgE antibody against milk and cow's hair antigens. 18 cases had IgE antibodies reacting with milk and 9 with cow's hair. There was correlation between the levels of these antibodies with the exception of two cases. The results give evidence that half of the asthmatic children allergic to milk will react with bronchospasm in the cases if they ar exposed to inhalation of cow's hair."} {"id": "PMID:162029", "title": "[E-rosette formation after liver transplantation (author's transl)].", "content": "In 1 patient with orthotopic liver transplantation E-rosette formation was investigated during a period of 16 months. The patient showed an average rate of rosette formation comparable to this of controls. Increased or decreased rates were connected to crises--cholangitis and rejection--in clinical currency.", "contents": "[E-rosette formation after liver transplantation (author's transl)]. In 1 patient with orthotopic liver transplantation E-rosette formation was investigated during a period of 16 months. The patient showed an average rate of rosette formation comparable to this of controls. Increased or decreased rates were connected to crises--cholangitis and rejection--in clinical currency."} {"id": "PMID:162030", "title": "[Examination of lymphokines in patients with hemodialysis (author's transl)].", "content": "The activity of LIF after Con A stimulation was examined in patients with hemodialysis and chronic uremia. It was found that LIF activity is reduced in uremia compared with healthy controls. The absolute number of T lymphocytes was reduced as well as the number of active E rosettes. An inhibitory effect was found in vitro by isolated middle molecules from uremic serum and ultrafiltrate. The LIF production of normal lymphocytes and the number of active rosettes are significantly reduced by substances isolated from serum and ultrafiltrate with molecular weight of 1 000 to 1 500 Dalton. The authors think that these uremic middle molecules are responsible for the already known reducing of immune response by uremia. The uremic substances are dialysable.", "contents": "[Examination of lymphokines in patients with hemodialysis (author's transl)]. The activity of LIF after Con A stimulation was examined in patients with hemodialysis and chronic uremia. It was found that LIF activity is reduced in uremia compared with healthy controls. The absolute number of T lymphocytes was reduced as well as the number of active E rosettes. An inhibitory effect was found in vitro by isolated middle molecules from uremic serum and ultrafiltrate. The LIF production of normal lymphocytes and the number of active rosettes are significantly reduced by substances isolated from serum and ultrafiltrate with molecular weight of 1 000 to 1 500 Dalton. The authors think that these uremic middle molecules are responsible for the already known reducing of immune response by uremia. The uremic substances are dialysable."} {"id": "PMID:162031", "title": "[Evaluation of lymphocyte transformation test: relationship between nucleus and cell sizes of PHA-stimulated lymphocyes (author's transl)].", "content": "A methodological comparision of evaluation of lymphocyte transformation test is described. Three experts examined smear-slides of cells from five lymphocyte cultures and the corresponding controls in a blind study. In the morphological differentiation of 100 cells per slide in comparison to 1 000 cells per slide it was found a good intraindividually but a unsatisfactory interindividually correlation. 1 000 cells from stimulated and non-stimulated cultures shows the greatest difference for the parameter \"total cell size\" and the lowest difference for the \"nucleus plasma relation\" by the planimetrically imeasurement.", "contents": "[Evaluation of lymphocyte transformation test: relationship between nucleus and cell sizes of PHA-stimulated lymphocyes (author's transl)]. A methodological comparision of evaluation of lymphocyte transformation test is described. Three experts examined smear-slides of cells from five lymphocyte cultures and the corresponding controls in a blind study. In the morphological differentiation of 100 cells per slide in comparison to 1 000 cells per slide it was found a good intraindividually but a unsatisfactory interindividually correlation. 1 000 cells from stimulated and non-stimulated cultures shows the greatest difference for the parameter \"total cell size\" and the lowest difference for the \"nucleus plasma relation\" by the planimetrically imeasurement."} {"id": "PMID:162034", "title": "ATP-ase activity and lipid content of erythrocytes in treatment of acute lymphoblastic leukemia in children.", "content": "In erythrocytes of children with the acute lymphoblastic leukemia the rise in total phospholipid content, confined predominantly to lecithin, the decrease of cholesterol/phospholipid ratio and the increase of the Mg++-activated ATP-ase activity was found prior to treatment. The abnormalities of the lipid composition were in general persistent also in remission. The activity of erythrocytes ATP-ase decreased to normal values after achievement of the reversion of clinical and hematological symptoms of the disease. The increase of the enzyme activity may be induced by the in vitro incubation of normal erythrocyte with the blood plasma of patients in the acute stage of lymphoblastic leukemia but not in remission.", "contents": "ATP-ase activity and lipid content of erythrocytes in treatment of acute lymphoblastic leukemia in children. In erythrocytes of children with the acute lymphoblastic leukemia the rise in total phospholipid content, confined predominantly to lecithin, the decrease of cholesterol/phospholipid ratio and the increase of the Mg++-activated ATP-ase activity was found prior to treatment. The abnormalities of the lipid composition were in general persistent also in remission. The activity of erythrocytes ATP-ase decreased to normal values after achievement of the reversion of clinical and hematological symptoms of the disease. The increase of the enzyme activity may be induced by the in vitro incubation of normal erythrocyte with the blood plasma of patients in the acute stage of lymphoblastic leukemia but not in remission."} {"id": "PMID:162036", "title": "Effects of thymidine analogues on murine and human cells.", "content": "Three mouse tumour cell lines grew continuously in 3 micro M 5-bromodeoxyuridine (BUdR). One line (MC-2) produced a retrovirus and altered in morphology in the presence of BUdR or 5-iododeoxyuridine (IUdR). These effects, which could be reversed by growth in normal medium were similar to those reported for the B-16 mouse melanoma line. The B-16 line used in this study, however, as well as a variety of human cells (six melanoma lines and three fibroblast strains), were much more sensitive to BUdR, 0.03-0.1 micro M being the maximum tolerated levels for continuous growth. No virus production or changes in morphology were induced in these cells by BUdR, deoxyuridine (UdR), 5-fluorodeoxyuridine (FUdR) or thymidine (TdR). The results of cell labelling and growth studies showed a correlation of incorporation of BUdR into DNA with toxicity. Compared on a competitive basis with 1 micro M TdR, the order of incorporation of 1 micro M nucleosides by two human cell lines was TdR = BUdR = IUdR greater than UdR greater than FUdR. In contrast to previous reports that FUdR is incorporated into RNA but not into DNA, half of the FUdR label was found in alkalistable, DNase-sensitive material. Over 90% of the other compounds was incorporated into DNA. All of the UdR and 60% of the IUdR label was incorporated as thymidine; this conversion could be inhibited by labelling in the presence of FUdR.", "contents": "Effects of thymidine analogues on murine and human cells. Three mouse tumour cell lines grew continuously in 3 micro M 5-bromodeoxyuridine (BUdR). One line (MC-2) produced a retrovirus and altered in morphology in the presence of BUdR or 5-iododeoxyuridine (IUdR). These effects, which could be reversed by growth in normal medium were similar to those reported for the B-16 mouse melanoma line. The B-16 line used in this study, however, as well as a variety of human cells (six melanoma lines and three fibroblast strains), were much more sensitive to BUdR, 0.03-0.1 micro M being the maximum tolerated levels for continuous growth. No virus production or changes in morphology were induced in these cells by BUdR, deoxyuridine (UdR), 5-fluorodeoxyuridine (FUdR) or thymidine (TdR). The results of cell labelling and growth studies showed a correlation of incorporation of BUdR into DNA with toxicity. Compared on a competitive basis with 1 micro M TdR, the order of incorporation of 1 micro M nucleosides by two human cell lines was TdR = BUdR = IUdR greater than UdR greater than FUdR. In contrast to previous reports that FUdR is incorporated into RNA but not into DNA, half of the FUdR label was found in alkalistable, DNase-sensitive material. Over 90% of the other compounds was incorporated into DNA. All of the UdR and 60% of the IUdR label was incorporated as thymidine; this conversion could be inhibited by labelling in the presence of FUdR."} {"id": "PMID:162038", "title": "Mg2+ and ATP effects on K+ activation of the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum.", "content": "ATP and the divalent cations Mg2+ and Ca2+ regulated K+ stimulation of the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum vesicles. Millimolar concentrations of total ATP increased the K+-stimulated ATPase activity of the Ca2+ pump by two mechanisms. First, ATP chelated free Mg2+ and, at low ionized Mg2+ concentrations, K+ was shown to be a potent activator of ATP hydrolysis. In the absence of K+ ionized Mg2+ activated the enzyme half-maximally at approximately 1 mM, whereas in the presence of K+ the concentration of ionized Mg2+ required for half-maximal activation was reduced at least 20-fold. Second MgATP apparently interacted directly with the enzyme at a low affinity nucleotide site to facilitate K+-stimulation. With a saturating concentration of ionized Mg2+, stimulation by K+ was 2-fold, but only when the MgATP concentration was greater than 2 mM. Hill plots showed that K+ increased the concentration of MgATP required for half-maximal enzymic activation approx. 3-fold. Activation of K+-stimulated ATPase activity by Ca2+ was maximal at an ionized Ca2+ concentration of approx. 1 microM. At very high concentrations of either Ca2+ or Mg2+, basal Ca2+-dependent ATPase activity persisted, but the enzymic response to K+ was completely inhibited. The results provide further evidence that the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum has distinct sites for monovalent cations, which in turn interact allosterically with other regulatory sites on the enzyme.", "contents": "Mg2+ and ATP effects on K+ activation of the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum. ATP and the divalent cations Mg2+ and Ca2+ regulated K+ stimulation of the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum vesicles. Millimolar concentrations of total ATP increased the K+-stimulated ATPase activity of the Ca2+ pump by two mechanisms. First, ATP chelated free Mg2+ and, at low ionized Mg2+ concentrations, K+ was shown to be a potent activator of ATP hydrolysis. In the absence of K+ ionized Mg2+ activated the enzyme half-maximally at approximately 1 mM, whereas in the presence of K+ the concentration of ionized Mg2+ required for half-maximal activation was reduced at least 20-fold. Second MgATP apparently interacted directly with the enzyme at a low affinity nucleotide site to facilitate K+-stimulation. With a saturating concentration of ionized Mg2+, stimulation by K+ was 2-fold, but only when the MgATP concentration was greater than 2 mM. Hill plots showed that K+ increased the concentration of MgATP required for half-maximal enzymic activation approx. 3-fold. Activation of K+-stimulated ATPase activity by Ca2+ was maximal at an ionized Ca2+ concentration of approx. 1 microM. At very high concentrations of either Ca2+ or Mg2+, basal Ca2+-dependent ATPase activity persisted, but the enzymic response to K+ was completely inhibited. The results provide further evidence that the Ca2+-transport ATPase of cardiac sarcoplasmic reticulum has distinct sites for monovalent cations, which in turn interact allosterically with other regulatory sites on the enzyme."} {"id": "PMID:162035", "title": "[Caudography with Dimer-X in the diagnosis of lumbar and sciatic pain syndromes of orthopedic interest. Report of 100 consecutive examinations].", "content": "It was found that the employment of Dimer-X (methylglucamine jocarmate) as contrast medium greatly reduced the frequency of secondary phenomena in 100 caudographies performed in subjects with lumbar and sciatic pain syndromes of orthopaedic interest. Comparison between the clinical, caudographic and surgical findings showed how contrastography offered highly accurate information in support of the clinical diagnosis of disk compression in case of sufficiently severe lumbar and sciatic pain.", "contents": "[Caudography with Dimer-X in the diagnosis of lumbar and sciatic pain syndromes of orthopedic interest. Report of 100 consecutive examinations]. It was found that the employment of Dimer-X (methylglucamine jocarmate) as contrast medium greatly reduced the frequency of secondary phenomena in 100 caudographies performed in subjects with lumbar and sciatic pain syndromes of orthopaedic interest. Comparison between the clinical, caudographic and surgical findings showed how contrastography offered highly accurate information in support of the clinical diagnosis of disk compression in case of sufficiently severe lumbar and sciatic pain."} {"id": "PMID:162039", "title": "Collection of Hordeum spontaneum C. Koch emend. Bacht. from Southwest Asia studied in the neighborhood of Moscow.", "content": "Wild barley Hordeum spontaneum C. emend. is of interest from several aspects (Bakhteev, 1974). It is not only a very near relative of cultivated barley H. sativum Jessen, but also a potentially very promising donor for use in hybridization. With these facts in mind and, in particular, recalling N. I. Vavilov's remarks [on the occasion of publication of R. E. Regel's article \"on the origin of cultivated barleys\" (1917)], appropriate investigations were started. In the present case 77 specimens of H. spontaneum, collected by S. Sakamoto (Japan) in the countries of South West Asia, were studied with reference to several morphological and biological features including winter hardiness.", "contents": "Collection of Hordeum spontaneum C. Koch emend. Bacht. from Southwest Asia studied in the neighborhood of Moscow. Wild barley Hordeum spontaneum C. emend. is of interest from several aspects (Bakhteev, 1974). It is not only a very near relative of cultivated barley H. sativum Jessen, but also a potentially very promising donor for use in hybridization. With these facts in mind and, in particular, recalling N. I. Vavilov's remarks [on the occasion of publication of R. E. Regel's article \"on the origin of cultivated barleys\" (1917)], appropriate investigations were started. In the present case 77 specimens of H. spontaneum, collected by S. Sakamoto (Japan) in the countries of South West Asia, were studied with reference to several morphological and biological features including winter hardiness."} {"id": "PMID:162045", "title": "The effects of methylnitrosourea on the immune system and hematopoietic system of adult specific pathogen free cats.", "content": "The effects of a single non-carcinogenic dose of 15 mg/kg methylnitrosourea (MNU) on the immune and hematopoietic systems of adult specific-pathogen-free (SPF) cats were determined. The cell-mediated-immune (CMI) system was markedly suppressed, as evidenced by: (i) Prolonged cutaneous allograft retention time (41-84 days); (ii) Decreased lymphocyte blast transformation response to mitogens (2% of pretreatment response to pokeweed mitogen or concanavalin A) and antigen (12% of untreated control cat response to keyhole limpet hemocyanin); (iii) Reduced number of absolute erythrocyte-rosetting T-cells in the peripheral blood. This immunosuppression lasted at least 3 months, the duration of the experiment. Suppression of the hematopoietic system was also noted as evidenced by: (i) Peripheral lymphopenia lasting 3 months and neutropenia lasting 3 weeks; (ii) Bone marrow hypocellularity lasting 3 weeks; (iii) Hypoplasia of neutrophilic precursors lasting 3 weeks and erythroid precursors lasting 4 days. It was concluded that a single non-carcinogenic dose of MNU induces a prolonged suppression of the CMI system and a brief suppression of hematopoiesis in adult SPF cats. The immunosuppression may in part be responsible for the previously observed increased susceptibility to feline leukemia virus infection and disease of adult SPF cats treated with MNU.", "contents": "The effects of methylnitrosourea on the immune system and hematopoietic system of adult specific pathogen free cats. The effects of a single non-carcinogenic dose of 15 mg/kg methylnitrosourea (MNU) on the immune and hematopoietic systems of adult specific-pathogen-free (SPF) cats were determined. The cell-mediated-immune (CMI) system was markedly suppressed, as evidenced by: (i) Prolonged cutaneous allograft retention time (41-84 days); (ii) Decreased lymphocyte blast transformation response to mitogens (2% of pretreatment response to pokeweed mitogen or concanavalin A) and antigen (12% of untreated control cat response to keyhole limpet hemocyanin); (iii) Reduced number of absolute erythrocyte-rosetting T-cells in the peripheral blood. This immunosuppression lasted at least 3 months, the duration of the experiment. Suppression of the hematopoietic system was also noted as evidenced by: (i) Peripheral lymphopenia lasting 3 months and neutropenia lasting 3 weeks; (ii) Bone marrow hypocellularity lasting 3 weeks; (iii) Hypoplasia of neutrophilic precursors lasting 3 weeks and erythroid precursors lasting 4 days. It was concluded that a single non-carcinogenic dose of MNU induces a prolonged suppression of the CMI system and a brief suppression of hematopoiesis in adult SPF cats. The immunosuppression may in part be responsible for the previously observed increased susceptibility to feline leukemia virus infection and disease of adult SPF cats treated with MNU."} {"id": "PMID:162047", "title": "Metallothionein: an exceptional metal thiolate protein.", "content": "Metallothioneins are unusual, low molecular weight proteins of extremely high sulphur and metabl content. They occur in substantial quantity and in multiple variant forms in parenchymatous tissues (liver, kidney, intestines) of vertebrates and certain microorganisms (Neurospora crassa, yeast). They are though to play a central role in the cellular metabolism of metals such as zinc, copper and cadmium. All mammalian forms studied are single chains with 20 cysteinyl residues among a total of 61 amino acid residues and highly characteristic amino acid sequences. Their most conspicuous common features are seven -Cys-X-Cys- sequences where X stands for an alphatic residue other than Cys. Together with additional cysteinyl residues located elsewhere in the chain and brought into juxtaposition by appropriate chain folding, these dithiol sequences are believed to form the basis of the trithiolate chelating structures typical of most of the six or seven metal-binding sites of the mammalian cadium- and/or zinc-containing metallothioneins. The positions of the cysteinyl residues are preserved in evolution: the copper-containing metallothionein from Neurospora crassa, containing only 25 amino acid residues, has a distribution of metal-binding cysteinyl residues identical to that of the N-terminal portion of the mammalian chains. The detailed physiological role of metallothionein remains to be clarified but its biosynthesis is known to be modulated by nutritional and endocrine factors. Recent evidence suggests that metallothionein is a critical determinant in the homeostasis of zinc.", "contents": "Metallothionein: an exceptional metal thiolate protein. Metallothioneins are unusual, low molecular weight proteins of extremely high sulphur and metabl content. They occur in substantial quantity and in multiple variant forms in parenchymatous tissues (liver, kidney, intestines) of vertebrates and certain microorganisms (Neurospora crassa, yeast). They are though to play a central role in the cellular metabolism of metals such as zinc, copper and cadmium. All mammalian forms studied are single chains with 20 cysteinyl residues among a total of 61 amino acid residues and highly characteristic amino acid sequences. Their most conspicuous common features are seven -Cys-X-Cys- sequences where X stands for an alphatic residue other than Cys. Together with additional cysteinyl residues located elsewhere in the chain and brought into juxtaposition by appropriate chain folding, these dithiol sequences are believed to form the basis of the trithiolate chelating structures typical of most of the six or seven metal-binding sites of the mammalian cadium- and/or zinc-containing metallothioneins. The positions of the cysteinyl residues are preserved in evolution: the copper-containing metallothionein from Neurospora crassa, containing only 25 amino acid residues, has a distribution of metal-binding cysteinyl residues identical to that of the N-terminal portion of the mammalian chains. The detailed physiological role of metallothionein remains to be clarified but its biosynthesis is known to be modulated by nutritional and endocrine factors. Recent evidence suggests that metallothionein is a critical determinant in the homeostasis of zinc."} {"id": "PMID:162067", "title": "Studies directed toward the total synthesis of antibiotics: (+)-spectinomycin.", "content": "The presence of a dioxaspiro or a fused bicyclic ring system resulting from a diastereoselective intramolecular acetalization of keto diol or keto alcohol units respectively, is a unique structural feature among a number of biologically important natural products. The particular bond arrangement around the ketal carbon atom is, in part, a reflection of the preference for anomeric stereoselection in nature, either at the site of acetalization or in its vicinity. This phenomenon manifests itself in the constitutional structures of several ionophores (polyether type), in the antibiotic spectinomycin as well as other natural products. Synthetic efforts in this area will be discussed, with particular emphasis on spectinomycin as a challenging target.", "contents": "Studies directed toward the total synthesis of antibiotics: (+)-spectinomycin. The presence of a dioxaspiro or a fused bicyclic ring system resulting from a diastereoselective intramolecular acetalization of keto diol or keto alcohol units respectively, is a unique structural feature among a number of biologically important natural products. The particular bond arrangement around the ketal carbon atom is, in part, a reflection of the preference for anomeric stereoselection in nature, either at the site of acetalization or in its vicinity. This phenomenon manifests itself in the constitutional structures of several ionophores (polyether type), in the antibiotic spectinomycin as well as other natural products. Synthetic efforts in this area will be discussed, with particular emphasis on spectinomycin as a challenging target."} {"id": "PMID:162070", "title": "[Ulcerative contact dermitis caused by premixed concrete (cement burns)].", "content": "Cement dermatitis manifests clinically as a chronic dermatitis of irritative character, due to its alkaline nature and as allergic contact dermatitis produced by sensitization to chromium and cobalt occurring as trace elements. the present report deals with a mason without previous dermatitis, presenting bullae, ulcers and necrosis in lower limbs, short time after incidental contact at work, with premixed concrete. The clinical manifestations, such as short evolution, clear limitation to sites in close contact with concrete, negativity to standard patch testing and good prognosis with early treatment, are mentioned. The acute irritant nature of the disease is clear, in opposition to the classical manifestations of cement dermatitis. The need of studies of the chemical properties of this material including pH, alkalinity and the possible roll of additives employed, is part of the strategy for prevention of occupational dermatitis in the building trade, which should include also, information of hazards and proper training in their trade.", "contents": "[Ulcerative contact dermitis caused by premixed concrete (cement burns)]. Cement dermatitis manifests clinically as a chronic dermatitis of irritative character, due to its alkaline nature and as allergic contact dermatitis produced by sensitization to chromium and cobalt occurring as trace elements. the present report deals with a mason without previous dermatitis, presenting bullae, ulcers and necrosis in lower limbs, short time after incidental contact at work, with premixed concrete. The clinical manifestations, such as short evolution, clear limitation to sites in close contact with concrete, negativity to standard patch testing and good prognosis with early treatment, are mentioned. The acute irritant nature of the disease is clear, in opposition to the classical manifestations of cement dermatitis. The need of studies of the chemical properties of this material including pH, alkalinity and the possible roll of additives employed, is part of the strategy for prevention of occupational dermatitis in the building trade, which should include also, information of hazards and proper training in their trade."} {"id": "PMID:162071", "title": "[Scleroatrophying and degenerative keratodermic genodermatosis of the extremities].", "content": "A case of a picture described by Huriez et al. under the title of scleatrophying and keratodermic genodermatosis of the limbs usually degenerative is presented. In the genealogic study it was observed that seven out of the sixteen members that belonged to this primary family group were affected or probably affected and it is stressed that one of them died from metastasis of spinocellular epithelioma.", "contents": "[Scleroatrophying and degenerative keratodermic genodermatosis of the extremities]. A case of a picture described by Huriez et al. under the title of scleatrophying and keratodermic genodermatosis of the limbs usually degenerative is presented. In the genealogic study it was observed that seven out of the sixteen members that belonged to this primary family group were affected or probably affected and it is stressed that one of them died from metastasis of spinocellular epithelioma."} {"id": "PMID:162072", "title": "Physiotherapy in certain aspects of psychosomatic medicine.", "content": "The author describes a combined approach, called psychomotoric treatment, for patients with emotionally conditioned, somatic symptoms, such as headache, backache, neck-shoulder-arm pains, postural disorders and inhibited respiration. Many of these patients have previously been treated in vain with tranquilizers and ordinary physiotherapy. The physiotherapeutic part of the treatment (psychomotoric physiotherapy) is based on a comprehensive view of the muscular apparatus and functioning as a whole with emphasis on correction of postural disorders and liberation of respiration. It should also include close cooperation with the doctor, who may be called upon when emotional inhibition impedes further progress of the physiotherapy. The main indication area for this treatment is the clientele of the general practitioner. Patients with clear psychiatric symptoms should be treated only if anchored in a secure psychotherapeutic situation.", "contents": "Physiotherapy in certain aspects of psychosomatic medicine. The author describes a combined approach, called psychomotoric treatment, for patients with emotionally conditioned, somatic symptoms, such as headache, backache, neck-shoulder-arm pains, postural disorders and inhibited respiration. Many of these patients have previously been treated in vain with tranquilizers and ordinary physiotherapy. The physiotherapeutic part of the treatment (psychomotoric physiotherapy) is based on a comprehensive view of the muscular apparatus and functioning as a whole with emphasis on correction of postural disorders and liberation of respiration. It should also include close cooperation with the doctor, who may be called upon when emotional inhibition impedes further progress of the physiotherapy. The main indication area for this treatment is the clientele of the general practitioner. Patients with clear psychiatric symptoms should be treated only if anchored in a secure psychotherapeutic situation."} {"id": "PMID:162075", "title": "Myocardial contractility: non-invasive assessment after cardiac surgery.", "content": "The shape of the carotid blood-flow signal in the assessment of myocardial contractility is important. The non-invasive electromagnetic method permits the measurement of the pulsatile carotid flow rate and thus to estimate the maximum blood flow acceleration (max. dF/dt), which is directly related to myocardial contractility. The electromagnetic flowmeter method, routinely used in the superficial arteries of arteriosclerotic patients, has been modified to record the blood flow rate in the carotid artery. Two ECG electrodes on both sides of the common carotid artery record the signal given by a small magnet located above the electrodes. Using this method, we have studied the effects of isoprenaline infusion in a normal subject. In patients after cardiac surgery we measured max. dF/dt in the region of the carotid artery and compared changes in it with parameters obtained by invasive methods such as the cardiac index, and the pulmonary and systemic pressures. The first results of blood flow recordings in the ascending aorta are presented here.", "contents": "Myocardial contractility: non-invasive assessment after cardiac surgery. The shape of the carotid blood-flow signal in the assessment of myocardial contractility is important. The non-invasive electromagnetic method permits the measurement of the pulsatile carotid flow rate and thus to estimate the maximum blood flow acceleration (max. dF/dt), which is directly related to myocardial contractility. The electromagnetic flowmeter method, routinely used in the superficial arteries of arteriosclerotic patients, has been modified to record the blood flow rate in the carotid artery. Two ECG electrodes on both sides of the common carotid artery record the signal given by a small magnet located above the electrodes. Using this method, we have studied the effects of isoprenaline infusion in a normal subject. In patients after cardiac surgery we measured max. dF/dt in the region of the carotid artery and compared changes in it with parameters obtained by invasive methods such as the cardiac index, and the pulmonary and systemic pressures. The first results of blood flow recordings in the ascending aorta are presented here."} {"id": "PMID:162080", "title": "Genetic markers and leprosy in South African negroes: Part II. Erythrocyte enzyme polymorphisms.", "content": "The phenotype frequencies of the erythrocyte enzyme polymorphisms acid phosphatase (aP), phosphoglucomutase loci 1 and 2 (PGM1 and PGM2), adenylate kinase (AK), adenosine desaminase (ADA), esterase D (EsD) and 6-phosphogluconate dehydrogenase (6-PGD) were determined on a sample of 234-248 South African Negroes with leprosy. These results were compared with data of 841--997 healthy Negro controls of similar geographical and ethnic origin, in order to determine whether or not any association exists between specific phenotypes and the manifestation of leprosy. A part of the data included in the present study were compared with the data of a similar comparative analysis on Mozambican Negroes. With regard to the polymorphisms aP, PGM1 and PGM2, the results derived from South Africa and Mozambique exhibit reverse patterns of deviations from the null hypothesis. From this it does not appear justified to postulate an association between these genetic markers and the occurrence of leprosy. For the enzyme polymorphisms ADA, AK and EsD (data are confined to South African Negroes only) the distribution of phenotypes between patients and controls was very similar. The differences were not statistically significant. However, observations on the 6-PGD polymorphism (data are confined to South African Negroes only) showed an excess of phenotype PGD A among leprosy patients as compared with controls. The difference was statistically highly significant. Further studies based on additional samples are required to substantiate whether or not the statistical outcome reflects a true association between this phenotype and leprosy.", "contents": "Genetic markers and leprosy in South African negroes: Part II. Erythrocyte enzyme polymorphisms. The phenotype frequencies of the erythrocyte enzyme polymorphisms acid phosphatase (aP), phosphoglucomutase loci 1 and 2 (PGM1 and PGM2), adenylate kinase (AK), adenosine desaminase (ADA), esterase D (EsD) and 6-phosphogluconate dehydrogenase (6-PGD) were determined on a sample of 234-248 South African Negroes with leprosy. These results were compared with data of 841--997 healthy Negro controls of similar geographical and ethnic origin, in order to determine whether or not any association exists between specific phenotypes and the manifestation of leprosy. A part of the data included in the present study were compared with the data of a similar comparative analysis on Mozambican Negroes. With regard to the polymorphisms aP, PGM1 and PGM2, the results derived from South Africa and Mozambique exhibit reverse patterns of deviations from the null hypothesis. From this it does not appear justified to postulate an association between these genetic markers and the occurrence of leprosy. For the enzyme polymorphisms ADA, AK and EsD (data are confined to South African Negroes only) the distribution of phenotypes between patients and controls was very similar. The differences were not statistically significant. However, observations on the 6-PGD polymorphism (data are confined to South African Negroes only) showed an excess of phenotype PGD A among leprosy patients as compared with controls. The difference was statistically highly significant. Further studies based on additional samples are required to substantiate whether or not the statistical outcome reflects a true association between this phenotype and leprosy."} {"id": "PMID:162078", "title": "[Electromyographic study of sciatica caused by lumbosacral disk hernia. Apropos of 40 cases with operative findings].", "content": "The Authors present the electromyographic study of 40 cases of low-back and sciatic pain due to lumbar herniation of the intervertebral disk after surgical checking. The E.M.G. parameters, which are thought to be more valid in order to make a diagnosis of the motor nerve-root pain and choose the test muscles to be examined, are shown here. Following the data of scientific publications, a special emphasis is put on the usefulness of the this check-up in order to supply important elements for the evaluation of the degree and position of the nerve-root damage.", "contents": "[Electromyographic study of sciatica caused by lumbosacral disk hernia. Apropos of 40 cases with operative findings]. The Authors present the electromyographic study of 40 cases of low-back and sciatic pain due to lumbar herniation of the intervertebral disk after surgical checking. The E.M.G. parameters, which are thought to be more valid in order to make a diagnosis of the motor nerve-root pain and choose the test muscles to be examined, are shown here. Following the data of scientific publications, a special emphasis is put on the usefulness of the this check-up in order to supply important elements for the evaluation of the degree and position of the nerve-root damage."} {"id": "PMID:162095", "title": "Xanthogranulomatous lymphadenitis.", "content": "A case of an unusual type of granulomatous lymphadenitis, initially suspected of being a malignant lymphoma, is reported. Histologically, this lesion shows a striking xanthomatous appearance, due to collections of foamy histiocytes interspersed with chronic inflammatory cells, and resulting in a storage-like aspect. Evidence indicates that this process merely represents the reabsorption and healing phases of an acute suppurative lymphadenitis, with histopathologic features comparable to those of xanthogranulomatous pyelonephritis. The term xanthogranulomatous lymphadenitis is suggested for this previously inadequately described lesion, and the likely non-specific degenerative character of the xanthomatous response is stressed.", "contents": "Xanthogranulomatous lymphadenitis. A case of an unusual type of granulomatous lymphadenitis, initially suspected of being a malignant lymphoma, is reported. Histologically, this lesion shows a striking xanthomatous appearance, due to collections of foamy histiocytes interspersed with chronic inflammatory cells, and resulting in a storage-like aspect. Evidence indicates that this process merely represents the reabsorption and healing phases of an acute suppurative lymphadenitis, with histopathologic features comparable to those of xanthogranulomatous pyelonephritis. The term xanthogranulomatous lymphadenitis is suggested for this previously inadequately described lesion, and the likely non-specific degenerative character of the xanthomatous response is stressed."} {"id": "PMID:162096", "title": "Shwachman's syndrome and leukaemia.", "content": "The clinical and morphological characteristics of Shwachman's syndrome (exocrine pancreatic insufficiency, pancytopenia, skeletal changes) were observed in a boy who, at the age of 8 years, developed a juvenile form of chronic myeloic leukemia which did not respond to cytostatic treatment. Autopsy revealed a striking lipomatous atrophy of the pancreas, defects in the ossification zones of the bones and marked dwarfism. In addition there was leukaemic infiltration of the pancreas, the spleen, the liver and the lymph nodes. The association of Shwachman's syndrome with leukaemia is a rare, but remarkable complication of this entity because of its relationship to the preceeding pancytopenia. Thorough follow-up of the haematological status of patients with Shwachman's syndrome is recommended.", "contents": "Shwachman's syndrome and leukaemia. The clinical and morphological characteristics of Shwachman's syndrome (exocrine pancreatic insufficiency, pancytopenia, skeletal changes) were observed in a boy who, at the age of 8 years, developed a juvenile form of chronic myeloic leukemia which did not respond to cytostatic treatment. Autopsy revealed a striking lipomatous atrophy of the pancreas, defects in the ossification zones of the bones and marked dwarfism. In addition there was leukaemic infiltration of the pancreas, the spleen, the liver and the lymph nodes. The association of Shwachman's syndrome with leukaemia is a rare, but remarkable complication of this entity because of its relationship to the preceeding pancytopenia. Thorough follow-up of the haematological status of patients with Shwachman's syndrome is recommended."} {"id": "PMID:162097", "title": "Liposarcoma of the breast. Case report and review of the literature.", "content": "A case of primary liposarcoma of the breast in a 65-years-old woman is described by light- and electron microscopy. The patient had previously had a cystosarcoma phyllodes removed from the same area. A review of the literature showed 34 previously published cases of liposarcoma of the breast, which regarding age distribution, histological type and pattern of metastasis corresponded to liposarcomas of the lower limbs.", "contents": "Liposarcoma of the breast. Case report and review of the literature. A case of primary liposarcoma of the breast in a 65-years-old woman is described by light- and electron microscopy. The patient had previously had a cystosarcoma phyllodes removed from the same area. A review of the literature showed 34 previously published cases of liposarcoma of the breast, which regarding age distribution, histological type and pattern of metastasis corresponded to liposarcomas of the lower limbs."} {"id": "PMID:162098", "title": "Light and electron microscopic studies on rat arterial lesions induced by experimental arterial contraction.", "content": "Experimental contraction was produced in the rat mesenteric arteries and the arterial segments were studied morphologically. When the rat mesenteric artery was exposed in physiological saline solution at 37 degrees C and 2-3 mg of methoxamine hydrochloride (10 mg/ml) was dripped onto it, intense contraction was observed for about 30 min but elevation in blood pressure was slight. During the contraction, numerous vacuoles were seen in the medial smooth muscle cells of the arterial segments, and these vacuoles were shown electron microscopically to have double unit membranes, indicating that they were formed by herniation of a part of the adjacent smooth muscle cell body. In the arteries 1-6 h after the end of the contraction, cellular, nuclear and vacuolar membranes and myofilaments of the medial muscle cells were partially lost. 12-24 h after the contraction the arteries exhibited necrosis and desquamation of endothelial cells and platelet adhesion. In the media, smooth muscle cells were completely deprived of cell membranes, myofilaments, nuclei, intracytoplasmic organelles other than mitochondria, and vacuolar membranes. The cytoplasm was filled with fine granular and granulo-vesicular material, and fibrin insudation was observed in these severely damaged cells. Arterial contraction may be an important factor in the induction of arterial lesions.", "contents": "Light and electron microscopic studies on rat arterial lesions induced by experimental arterial contraction. Experimental contraction was produced in the rat mesenteric arteries and the arterial segments were studied morphologically. When the rat mesenteric artery was exposed in physiological saline solution at 37 degrees C and 2-3 mg of methoxamine hydrochloride (10 mg/ml) was dripped onto it, intense contraction was observed for about 30 min but elevation in blood pressure was slight. During the contraction, numerous vacuoles were seen in the medial smooth muscle cells of the arterial segments, and these vacuoles were shown electron microscopically to have double unit membranes, indicating that they were formed by herniation of a part of the adjacent smooth muscle cell body. In the arteries 1-6 h after the end of the contraction, cellular, nuclear and vacuolar membranes and myofilaments of the medial muscle cells were partially lost. 12-24 h after the contraction the arteries exhibited necrosis and desquamation of endothelial cells and platelet adhesion. In the media, smooth muscle cells were completely deprived of cell membranes, myofilaments, nuclei, intracytoplasmic organelles other than mitochondria, and vacuolar membranes. The cytoplasm was filled with fine granular and granulo-vesicular material, and fibrin insudation was observed in these severely damaged cells. Arterial contraction may be an important factor in the induction of arterial lesions."} {"id": "PMID:162099", "title": "The role of myoepithelial cells in the morphogenesis of induced mammary tumours.", "content": "The localization and cytomorphology of myoepithelial (ME) cells and their role in the morphogenesis of the mammary gland tumours of Wistar rats induced by 7,12-Dimethylbenz-a-anthracene-DMBA- were studied. Cells which do not participate in secretion and contain cytoplasmic myofibrillar bundles in a typical arrangement are considered to be of ME origin. In the histogenesis of induced mammary gland tumours no difinite role can be attributed to mature ME cells or their precursors. Decreased differentiation is associated with reduced numbers of ME cells. No ME cells can be detected in the anaplastic, stromafree portions of the solid tumour. The sarcomatous component of the induced carcinosarcomas originates from connective tissue. ME cells may give rise to leiomyoma-like tumours comparable with the human benign mammary myoepithelioma. The atrophic areas of mammary gland tumours consisted mostly of preserved ME cells. The ME cells of induced mammary gland tumours were, in every respect, identical with the normal ME cells of control mammary glands.", "contents": "The role of myoepithelial cells in the morphogenesis of induced mammary tumours. The localization and cytomorphology of myoepithelial (ME) cells and their role in the morphogenesis of the mammary gland tumours of Wistar rats induced by 7,12-Dimethylbenz-a-anthracene-DMBA- were studied. Cells which do not participate in secretion and contain cytoplasmic myofibrillar bundles in a typical arrangement are considered to be of ME origin. In the histogenesis of induced mammary gland tumours no difinite role can be attributed to mature ME cells or their precursors. Decreased differentiation is associated with reduced numbers of ME cells. No ME cells can be detected in the anaplastic, stromafree portions of the solid tumour. The sarcomatous component of the induced carcinosarcomas originates from connective tissue. ME cells may give rise to leiomyoma-like tumours comparable with the human benign mammary myoepithelioma. The atrophic areas of mammary gland tumours consisted mostly of preserved ME cells. The ME cells of induced mammary gland tumours were, in every respect, identical with the normal ME cells of control mammary glands."} {"id": "PMID:162100", "title": "Primary malignant melanoma of the esophagus.", "content": "A case of primary malignant melanoma of the esophagus in a 74-year-old male is described. There was a diffuse pigmentation of the lower third of the esophagus macroscopically. Sections from this area revealed melanocytes in the basal layer of the epithelium. This melanosis was not caused by malignant melanoma cells, but obviously by preexisting ectopic and pigmented melanocytes a condition for which the term \"esophageal melanocytosis\" is proposed. It is suggested that esophageal melanocytosis as well as the presence of junctional changes may determine the primary nature of malignant melanoma of the esophagus. Furthermore, in order to outline the histologic criteria and the pathological features of primary esophageal melanomas, 64 cases have been reviewed.", "contents": "Primary malignant melanoma of the esophagus. A case of primary malignant melanoma of the esophagus in a 74-year-old male is described. There was a diffuse pigmentation of the lower third of the esophagus macroscopically. Sections from this area revealed melanocytes in the basal layer of the epithelium. This melanosis was not caused by malignant melanoma cells, but obviously by preexisting ectopic and pigmented melanocytes a condition for which the term \"esophageal melanocytosis\" is proposed. It is suggested that esophageal melanocytosis as well as the presence of junctional changes may determine the primary nature of malignant melanoma of the esophagus. Furthermore, in order to outline the histologic criteria and the pathological features of primary esophageal melanomas, 64 cases have been reviewed."} {"id": "PMID:162101", "title": "[Cytoenzymological, immunological and scanning electron microscopic studies on 49 cases (author's transl)].", "content": "Light cytology, enzymology, immunofluorescence and scanning electron microscopy have been performed on 49 bronchoalveolar fluids recovered by bronchoscopic lavage. The patients had the following lung diseases: infectious pneumonitis (19 cases), pulmonary fibrosis (13 cases) including 5 sarco\u00efdosis, 3 idiopathic pulmonary fibrosis and 5 silicosis, hypersensitivity pneumonitis (5 cases) and miscellaneous lung tumors (12 cases). Cytologic studies in comparison with clinical aspects show 4 groups: Group I (chronic bronchopneumopathy and inactive fibrosis) presents numerous cells but few lymphocytes (less than 5%); in Group II (evolutive fibrosis) have an increase percentage of lymphocytes (20%); in Group III (hypersensitivity pneumonitis) is observed a very high percentage of lymphocytes (45%); and in Group IV (cancerous lung diseases) values are not far from normal percentage except for lymphomas. Small macrophages (diameter: 10 microns) with a central monocyto\u00efde nucleus and few cytoplasma, are abundant in groups II and III where lymphocytosis is higher. Scanning electron microscopy shows irregular and rough surface, and numerous spontaneous adherences with erythrocytes, lymphocytes, or bacterias. Enzymatic activity (acid hydrolase, esterase, oxydase) increases in these cells. Lymphocytes have a smooth surface ovocative of T origin which is confirmed by granular acid phosphatase positivity and rosette forming test. Immunofluorescence shows positive granules with IgG, C1Q and C3 in macrophages only for Groups II and III while free immunoglobulins were present in the recovered lavage fluid.", "contents": "[Cytoenzymological, immunological and scanning electron microscopic studies on 49 cases (author's transl)]. Light cytology, enzymology, immunofluorescence and scanning electron microscopy have been performed on 49 bronchoalveolar fluids recovered by bronchoscopic lavage. The patients had the following lung diseases: infectious pneumonitis (19 cases), pulmonary fibrosis (13 cases) including 5 sarco\u00efdosis, 3 idiopathic pulmonary fibrosis and 5 silicosis, hypersensitivity pneumonitis (5 cases) and miscellaneous lung tumors (12 cases). Cytologic studies in comparison with clinical aspects show 4 groups: Group I (chronic bronchopneumopathy and inactive fibrosis) presents numerous cells but few lymphocytes (less than 5%); in Group II (evolutive fibrosis) have an increase percentage of lymphocytes (20%); in Group III (hypersensitivity pneumonitis) is observed a very high percentage of lymphocytes (45%); and in Group IV (cancerous lung diseases) values are not far from normal percentage except for lymphomas. Small macrophages (diameter: 10 microns) with a central monocyto\u00efde nucleus and few cytoplasma, are abundant in groups II and III where lymphocytosis is higher. Scanning electron microscopy shows irregular and rough surface, and numerous spontaneous adherences with erythrocytes, lymphocytes, or bacterias. Enzymatic activity (acid hydrolase, esterase, oxydase) increases in these cells. Lymphocytes have a smooth surface ovocative of T origin which is confirmed by granular acid phosphatase positivity and rosette forming test. Immunofluorescence shows positive granules with IgG, C1Q and C3 in macrophages only for Groups II and III while free immunoglobulins were present in the recovered lavage fluid."} {"id": "PMID:162102", "title": "Ultrastructure of clear cell carcinoma of the ovary. Case report and review of the literature.", "content": "The fine structure of an ovarian clear cell carcinoma in a 65 year old woman was analysed. The tumor cells were of both clear and \"hobnail\" types. Both were characterized by the presence of short microvilli, abundant glycogen granules, a well-developed granular endoplasmic reticulum and Golgi apparatus, scanty lysosomes and very few lipid bodies. The tubules and gland-like spaces were always separated from the stroma by a basement membrane. At ultrastructural level the tumor cells do not resemble at all those of cleaar cell renal carcinomas. On the other hand, their submicroscopic features are strongly similar to those of the clear cell tumors found elsewhere in the female genital tract, emphasizing therewith their very probable m\u00fcllerian origin. It is recommended to eliminate the term \"mesonephroma ovarii\" to designate the clear cell carcinomas of the ovary.", "contents": "Ultrastructure of clear cell carcinoma of the ovary. Case report and review of the literature. The fine structure of an ovarian clear cell carcinoma in a 65 year old woman was analysed. The tumor cells were of both clear and \"hobnail\" types. Both were characterized by the presence of short microvilli, abundant glycogen granules, a well-developed granular endoplasmic reticulum and Golgi apparatus, scanty lysosomes and very few lipid bodies. The tubules and gland-like spaces were always separated from the stroma by a basement membrane. At ultrastructural level the tumor cells do not resemble at all those of cleaar cell renal carcinomas. On the other hand, their submicroscopic features are strongly similar to those of the clear cell tumors found elsewhere in the female genital tract, emphasizing therewith their very probable m\u00fcllerian origin. It is recommended to eliminate the term \"mesonephroma ovarii\" to designate the clear cell carcinomas of the ovary."} {"id": "PMID:162104", "title": "[Efficiency of early therapy in mentally retarded children].", "content": "Although basic experimental results suggest how much the psychophysical organism can be influenced in particular during early childhood, the question of the effectiveness of early therapy in particular cases nevertheless comes up. First the problem of early therapeutic programs with regard to method and controllability is discussed. Then a concept for early therapy, the Munich \"Developmental Therapy\" is reported. Finally a report is given on a study of 151 Down's syndrome children, 0-3 years old, in whom the effectiveness of an early developmental therapy could be proved. A follow-up study of 15 children, 7-10 years old, in comparison with a parallel control group, confirmed these results.", "contents": "[Efficiency of early therapy in mentally retarded children]. Although basic experimental results suggest how much the psychophysical organism can be influenced in particular during early childhood, the question of the effectiveness of early therapy in particular cases nevertheless comes up. First the problem of early therapeutic programs with regard to method and controllability is discussed. Then a concept for early therapy, the Munich \"Developmental Therapy\" is reported. Finally a report is given on a study of 151 Down's syndrome children, 0-3 years old, in whom the effectiveness of an early developmental therapy could be proved. A follow-up study of 15 children, 7-10 years old, in comparison with a parallel control group, confirmed these results."} {"id": "PMID:162105", "title": "[Psychological problems of parents and therapists in the early education of physically handicapped children].", "content": "The traumatic experience of the child's handicap creates psychological problems not only for the parents, but also for the therapists involved in early stimulation. Since successful stimulation can be hindered by these difficulties, it is importnat that they are recognized as early as possible, and minimized by appropriate responses from the personnel involved. A prerequisite to overcoming these difficulties is therefore the training of professional staff in the areas of psychodynamics and self-experience.", "contents": "[Psychological problems of parents and therapists in the early education of physically handicapped children]. The traumatic experience of the child's handicap creates psychological problems not only for the parents, but also for the therapists involved in early stimulation. Since successful stimulation can be hindered by these difficulties, it is importnat that they are recognized as early as possible, and minimized by appropriate responses from the personnel involved. A prerequisite to overcoming these difficulties is therefore the training of professional staff in the areas of psychodynamics and self-experience."} {"id": "PMID:162106", "title": "[The Exeter program of home visits by \"developmental therapists\". Suggestions on the procedure to follow in the presence of severe handicap in a child of less than 3 years].", "content": "The principal idea expressed in this paper is that there is a period of time between the birth of a child with a severe handicap and the realization of the parents that the child may need their specific individual attention to his general development because of that handicap: that this coincides with the period of time usually taken by doctors for diagnosis of all the aspects contributing to the developmental delay; that these periods are both likely to be two to three years. Intervention by a competent developmental therapist working weekly in the home is of specific aid to the infant, to the parents and to the doctor during this period.", "contents": "[The Exeter program of home visits by \"developmental therapists\". Suggestions on the procedure to follow in the presence of severe handicap in a child of less than 3 years]. The principal idea expressed in this paper is that there is a period of time between the birth of a child with a severe handicap and the realization of the parents that the child may need their specific individual attention to his general development because of that handicap: that this coincides with the period of time usually taken by doctors for diagnosis of all the aspects contributing to the developmental delay; that these periods are both likely to be two to three years. Intervention by a competent developmental therapist working weekly in the home is of specific aid to the infant, to the parents and to the doctor during this period."} {"id": "PMID:162107", "title": "[Integration of handicapped children in normal schools in Bologna, Italy].", "content": "In Bologna and other cities of Northern Italy efforts are made to integrate all handicapped children in the normal classes of the public school. The arrangements necessary for a successful integration are described.", "contents": "[Integration of handicapped children in normal schools in Bologna, Italy]. In Bologna and other cities of Northern Italy efforts are made to integrate all handicapped children in the normal classes of the public school. The arrangements necessary for a successful integration are described."} {"id": "PMID:162108", "title": "[Integration of chronically ill and handicapped children in Sweden].", "content": "A differentiated system is applied in Sweden with individual integration for some children, special classes in normal schools for others and special schools for the rest.", "contents": "[Integration of chronically ill and handicapped children in Sweden]. A differentiated system is applied in Sweden with individual integration for some children, special classes in normal schools for others and special schools for the rest."} {"id": "PMID:162110", "title": "[The Honeylands Project, Exeter: care for mentally, physically and socially handicapped children and their families].", "content": "The Children's Hospital Honeylands is taking care of some 250 mentally, physically and socially handicapped 0 to 12 years old children and their families. It provides overnight hospital accommodation for thirty, and day care facilities for up to fifty children. Services provided are specific therapy, playgroups, education and regular home-visiting for the preschool children, and residential relief for the families. There are 6000 day and 6000 night attendances a year. The support service has evolved from the children's ward of a District Hospital, located in a city of 100,000 and serving a district of 300,000. Expressed parental needs have been the source of evolutionary change. A ten-year experience has shown that early and active involvement of the parents in the therapy and planning for their child keeps the demand for permanent residential placements of handicapped children very low. There are one quarter the number of mentally handicapped children in permanent residential care in the Exeter & East Devon Health District, compared to the national average. Whether Honeylands represents a model within the National Health Service for the family orientated care of handicapped children is at present under evaluation.", "contents": "[The Honeylands Project, Exeter: care for mentally, physically and socially handicapped children and their families]. The Children's Hospital Honeylands is taking care of some 250 mentally, physically and socially handicapped 0 to 12 years old children and their families. It provides overnight hospital accommodation for thirty, and day care facilities for up to fifty children. Services provided are specific therapy, playgroups, education and regular home-visiting for the preschool children, and residential relief for the families. There are 6000 day and 6000 night attendances a year. The support service has evolved from the children's ward of a District Hospital, located in a city of 100,000 and serving a district of 300,000. Expressed parental needs have been the source of evolutionary change. A ten-year experience has shown that early and active involvement of the parents in the therapy and planning for their child keeps the demand for permanent residential placements of handicapped children very low. There are one quarter the number of mentally handicapped children in permanent residential care in the Exeter & East Devon Health District, compared to the national average. Whether Honeylands represents a model within the National Health Service for the family orientated care of handicapped children is at present under evaluation."} {"id": "PMID:162112", "title": "[Experimental and theoretical aspects of the pathogenesis and prevention of caries (author's transl)].", "content": "This article discusses the uses and possible ways of increasing the effectiveness of caries preventives. The authors describe the mechanisms of homeostasis and resistance of dental enamel and the ways in which these processes proceed in the production of caries and underscore the characteristics of enamel as a cell-free form of tissue which because of the lack of elements serving to receive biological information is only indirectly connected with neurohumoral regulatory mechanisms. Also, reasons are given for the necessity of making fundamental theoretical studies into both local and general measures of prevention of caries.", "contents": "[Experimental and theoretical aspects of the pathogenesis and prevention of caries (author's transl)]. This article discusses the uses and possible ways of increasing the effectiveness of caries preventives. The authors describe the mechanisms of homeostasis and resistance of dental enamel and the ways in which these processes proceed in the production of caries and underscore the characteristics of enamel as a cell-free form of tissue which because of the lack of elements serving to receive biological information is only indirectly connected with neurohumoral regulatory mechanisms. Also, reasons are given for the necessity of making fundamental theoretical studies into both local and general measures of prevention of caries."} {"id": "PMID:162113", "title": "[Fluoride contents of rat molars following the administration of amine-fluoride-containing caries preventives (author's transl)].", "content": "Experiments on fifty Wistar rats were conducted with the object of studying the incorporation of fluoride into the enamel of molars subsequent to the administration of amine-fluoride-containing caries preventives. - Use of two toothpastes with low fluoride contents of 0.125% and 0.18% F, respectively, and two higher-fluoride (1% F) solutions resulted in a marked increase in the concentration of fluoride in the superficial layers of dental enamel.", "contents": "[Fluoride contents of rat molars following the administration of amine-fluoride-containing caries preventives (author's transl)]. Experiments on fifty Wistar rats were conducted with the object of studying the incorporation of fluoride into the enamel of molars subsequent to the administration of amine-fluoride-containing caries preventives. - Use of two toothpastes with low fluoride contents of 0.125% and 0.18% F, respectively, and two higher-fluoride (1% F) solutions resulted in a marked increase in the concentration of fluoride in the superficial layers of dental enamel."} {"id": "PMID:162115", "title": "[Abnormal courses of acute pyogenic soft-part infections in the maxillofacial and cervical regions (author's transl)].", "content": "The etiology and therapy of abnormal causes of pyogenic soft-part infections in the maxillofacial and cervical regions are discussed by reference to five case reports. Such clinical pictures usually result from a misinterpretation by the initially attending physician and consequent errors in treatment, from the indolence of patients, and from complicating conditions which are due especially to the particular disease agents involved, with one factor generally affecting the other. Today, even most serious disease pictures can be seen ruled to surgical and antibiotic treatment. In cases of doubt, tracheotomy should be performed before surgical cuts into abscesses are made especially where extensive suppuration involves the floor of the mouth, the parapharyngeal space, and the cervicovascular space.", "contents": "[Abnormal courses of acute pyogenic soft-part infections in the maxillofacial and cervical regions (author's transl)]. The etiology and therapy of abnormal causes of pyogenic soft-part infections in the maxillofacial and cervical regions are discussed by reference to five case reports. Such clinical pictures usually result from a misinterpretation by the initially attending physician and consequent errors in treatment, from the indolence of patients, and from complicating conditions which are due especially to the particular disease agents involved, with one factor generally affecting the other. Today, even most serious disease pictures can be seen ruled to surgical and antibiotic treatment. In cases of doubt, tracheotomy should be performed before surgical cuts into abscesses are made especially where extensive suppuration involves the floor of the mouth, the parapharyngeal space, and the cervicovascular space."} {"id": "PMID:162116", "title": "[Kasabach-Merritt syndrome as viewed from a surgical and stomatological standpoint (author's transl)].", "content": "The Kasaach-Merritt syndrome involves the very infrequent symptom complex of \"giant hemangioma--thrombocytopenia--coagulation disorder\". Hemorrhagic diathesis is here based on consumption coagulopathy. This paper reports upon secondary bleeding after extraction of a tooth in a 25-year-old male affected with this syndrome. Continuation or initiation of anticoagulant therapy is recommended for surgical stomatological treatment on an inpatient basis, and measures to be taken in connection with wound treatment are described.", "contents": "[Kasabach-Merritt syndrome as viewed from a surgical and stomatological standpoint (author's transl)]. The Kasaach-Merritt syndrome involves the very infrequent symptom complex of \"giant hemangioma--thrombocytopenia--coagulation disorder\". Hemorrhagic diathesis is here based on consumption coagulopathy. This paper reports upon secondary bleeding after extraction of a tooth in a 25-year-old male affected with this syndrome. Continuation or initiation of anticoagulant therapy is recommended for surgical stomatological treatment on an inpatient basis, and measures to be taken in connection with wound treatment are described."} {"id": "PMID:162117", "title": "[Angiomatous diseases in the maxillofacial region and their treatment in adults].", "content": "\"Angioma\"-situations in the newborn are common, but even in adults one may find more or less common situations, more or less difficult to manage. - In any way, like in the early childhood, the differentiation between inborn teleangiectatic or angiokeratotic nevi and the capillary angioma or angiomatous nevi is very important concerning the prognostic and therapeutic consequences. The real newborn capillary angiomas are selfhealing. Nearly they are not found in adults and otherwise surgically treated in the same simple matter as little teleangiectasias and the eruptive \"granuloma\" teleangiectaticum. On the other hand late tuberous alterations of non selfhealing naevus flammeus, naevus angiokeratoticus and the teleangiectatic \"angioma\" racemosum of the orofacial region give a slot of surgical problems and no sufficient effect to different kinds of radiotherapy. - These situations are presented, discussed and documented, moreover some rare uncommon situations, e.g. blue rubber-bleb nevus-syndroma, and angiokeratotic nevus together with different well checked therapeutic methods and results.", "contents": "[Angiomatous diseases in the maxillofacial region and their treatment in adults]. \"Angioma\"-situations in the newborn are common, but even in adults one may find more or less common situations, more or less difficult to manage. - In any way, like in the early childhood, the differentiation between inborn teleangiectatic or angiokeratotic nevi and the capillary angioma or angiomatous nevi is very important concerning the prognostic and therapeutic consequences. The real newborn capillary angiomas are selfhealing. Nearly they are not found in adults and otherwise surgically treated in the same simple matter as little teleangiectasias and the eruptive \"granuloma\" teleangiectaticum. On the other hand late tuberous alterations of non selfhealing naevus flammeus, naevus angiokeratoticus and the teleangiectatic \"angioma\" racemosum of the orofacial region give a slot of surgical problems and no sufficient effect to different kinds of radiotherapy. - These situations are presented, discussed and documented, moreover some rare uncommon situations, e.g. blue rubber-bleb nevus-syndroma, and angiokeratotic nevus together with different well checked therapeutic methods and results."} {"id": "PMID:162120", "title": "Demonstration of myo-inositol-1-phosphate synthase and its assumed defective variant in various Neurospora crassa strains by immunological methods.", "content": "Immunological experiments were performed to demonstrate myo-inositol-1-phosphate synthase (EC 5.5.1.4) and its assumed defective variant in various Neurospora crassa stains. An enzymatically inactive protein fraction was isolated from the inl-mutant by the same procedure as that of the enzyme. It consisted of several components by gel electrophoresis, and produced a positive immune reaction demonstrated by immunodiffusion using immune sera produced against the enzyme. Using immunodisc gel electrophoresis it produced an immunoprecipitate of slightly lower mobility than the enzyme itself. Similarly, positive immune reactions were obtained with the enzyme using immune sera produced against the protein fraction isolated from the inl- mutant. Enzyme activity was demonstrated both in a strain transformed by wild-type DNA and in a spontaneous revertant. The enzymes were subsequently isolated from both strains, and some properties were compared with those of the wild-type enzyme. The specific activities were lower but the Michaelis constants were nearly the same. The immunodisc gel electrophoretic patterns of these enzymes were similar to that of the protein fraction from the inositol requiring mutant.", "contents": "Demonstration of myo-inositol-1-phosphate synthase and its assumed defective variant in various Neurospora crassa strains by immunological methods. Immunological experiments were performed to demonstrate myo-inositol-1-phosphate synthase (EC 5.5.1.4) and its assumed defective variant in various Neurospora crassa stains. An enzymatically inactive protein fraction was isolated from the inl-mutant by the same procedure as that of the enzyme. It consisted of several components by gel electrophoresis, and produced a positive immune reaction demonstrated by immunodiffusion using immune sera produced against the enzyme. Using immunodisc gel electrophoresis it produced an immunoprecipitate of slightly lower mobility than the enzyme itself. Similarly, positive immune reactions were obtained with the enzyme using immune sera produced against the protein fraction isolated from the inl- mutant. Enzyme activity was demonstrated both in a strain transformed by wild-type DNA and in a spontaneous revertant. The enzymes were subsequently isolated from both strains, and some properties were compared with those of the wild-type enzyme. The specific activities were lower but the Michaelis constants were nearly the same. The immunodisc gel electrophoretic patterns of these enzymes were similar to that of the protein fraction from the inositol requiring mutant."} {"id": "PMID:162121", "title": "Functional investigations of isolated mitochondria under steady-state conditions by means of a perfusion technique.", "content": "It was observed that borosilicate glass prefilters have a high absorptive capacity for isolated rat-liver mitochondria and that this binding does not need any kind of chemical procedure. This observation has led to the development of a perifusion technique for isolated rat-liver mitochondria. During perifusion the mitochondria are immobilized on a prefilter. Their morphological and functional intactness is conserved. During the course of the perifusion no loss of marker enzymes (adenylate kinase and malate dehydrogenase) can be detected. The respiration rates in the controlled and the active state are similar to those observed in a conventional closed polarographic vessel. The respiratory control is maintained for more than 30 min. With the perifusion technique it is possible to adjust respiration rates to stationary steady states between the controlled and the active state. It was shown that the control of respiration by the extramitochondrial ATP/ADP ratio is independent of the succinate concentration in the range of 1 to 10 mM.", "contents": "Functional investigations of isolated mitochondria under steady-state conditions by means of a perfusion technique. It was observed that borosilicate glass prefilters have a high absorptive capacity for isolated rat-liver mitochondria and that this binding does not need any kind of chemical procedure. This observation has led to the development of a perifusion technique for isolated rat-liver mitochondria. During perifusion the mitochondria are immobilized on a prefilter. Their morphological and functional intactness is conserved. During the course of the perifusion no loss of marker enzymes (adenylate kinase and malate dehydrogenase) can be detected. The respiration rates in the controlled and the active state are similar to those observed in a conventional closed polarographic vessel. The respiratory control is maintained for more than 30 min. With the perifusion technique it is possible to adjust respiration rates to stationary steady states between the controlled and the active state. It was shown that the control of respiration by the extramitochondrial ATP/ADP ratio is independent of the succinate concentration in the range of 1 to 10 mM."} {"id": "PMID:162123", "title": "[Technical characteristics of an electromagnetic transducer of aortic flow, with reduced structure].", "content": "Sometimes a common probe of an electromagnetic flowmeter cannot be chronically placed around the aorta in the dog because its weight and shape can induce vascular injuries. Moreover it may occur that the record is disturbed by the movements of the probe around the vessel. The authors describe a new type probe that is capable to produce a reliable signal of the aortic blood flow, in spite of a reduced structure of its components. Obviously, such a signal, which is greater that the one produced by a coronary blood flow probe, must be properly amplified.", "contents": "[Technical characteristics of an electromagnetic transducer of aortic flow, with reduced structure]. Sometimes a common probe of an electromagnetic flowmeter cannot be chronically placed around the aorta in the dog because its weight and shape can induce vascular injuries. Moreover it may occur that the record is disturbed by the movements of the probe around the vessel. The authors describe a new type probe that is capable to produce a reliable signal of the aortic blood flow, in spite of a reduced structure of its components. Obviously, such a signal, which is greater that the one produced by a coronary blood flow probe, must be properly amplified."} {"id": "PMID:162124", "title": "Diamide effect on the ouabain-insensitive APTase activity of red cell membrane.", "content": "Membranes from human erythrocytes exhibit a marked decrease of the ouabain-insensitive ATPase activity and of the total membrane thiol content after treatment with diazenedicarboxylic acid bis(N,N-dimethylamide) (diamide). These effects increase with diamide concentrations up to 2-2.5 mM and are persistent after removal of the reagent. Treatment with 2,3-dihydroxy-1,4-dithiolbutane (dithioerythritol or DTE) reduced glutathione or 2-mercaptoethanol partially but significantly restores at about the same extent the ouabain-insensitive ATPase activity. These results indicate that the perturbation of the ATPase microenvironment caused by membrane thiol oxidation is at good extent responsible for alterations of the divalent cation-dependent ATPase activity.", "contents": "Diamide effect on the ouabain-insensitive APTase activity of red cell membrane. Membranes from human erythrocytes exhibit a marked decrease of the ouabain-insensitive ATPase activity and of the total membrane thiol content after treatment with diazenedicarboxylic acid bis(N,N-dimethylamide) (diamide). These effects increase with diamide concentrations up to 2-2.5 mM and are persistent after removal of the reagent. Treatment with 2,3-dihydroxy-1,4-dithiolbutane (dithioerythritol or DTE) reduced glutathione or 2-mercaptoethanol partially but significantly restores at about the same extent the ouabain-insensitive ATPase activity. These results indicate that the perturbation of the ATPase microenvironment caused by membrane thiol oxidation is at good extent responsible for alterations of the divalent cation-dependent ATPase activity."} {"id": "PMID:162125", "title": "Biological effect of a hypogeomagnetic environment on an organism.", "content": "In an age of a scientific and technical revolution, when many operators work in structures shielding the geomagnetic field (GMF) by a factor of 100 or more, the urgency of this problem is shown. To study the effect of a hypogeomagnetic environment on warm-blooded organisms, series of experiments were conducted on rabbits that passed through entire embryogenesis and grew to an age of one month in a shielded chamber where the GMF was reduced by a factor of 600. The results obtained confirm that the effect of the GMF is needed for normal development of the organism. Degenerative disturbances in the liver, myocardium, and gastrointestinal tract were noted in animals reared in a reduced GMF. Structural and energy metabolism are disturbed, and the marked inhibition of activity of the investigated enzymatic systems, except the glycolytic, is shown. Changes in the motor activity of the experimental animals and insufficiency of the neuromuscular apparatus were revealed. The mortality rate among the experimental animals was statistically higher than for the controls. The authors raise the question of the need for further comprehensive investigations of the established effects of the hypogeomagnetic environment.", "contents": "Biological effect of a hypogeomagnetic environment on an organism. In an age of a scientific and technical revolution, when many operators work in structures shielding the geomagnetic field (GMF) by a factor of 100 or more, the urgency of this problem is shown. To study the effect of a hypogeomagnetic environment on warm-blooded organisms, series of experiments were conducted on rabbits that passed through entire embryogenesis and grew to an age of one month in a shielded chamber where the GMF was reduced by a factor of 600. The results obtained confirm that the effect of the GMF is needed for normal development of the organism. Degenerative disturbances in the liver, myocardium, and gastrointestinal tract were noted in animals reared in a reduced GMF. Structural and energy metabolism are disturbed, and the marked inhibition of activity of the investigated enzymatic systems, except the glycolytic, is shown. Changes in the motor activity of the experimental animals and insufficiency of the neuromuscular apparatus were revealed. The mortality rate among the experimental animals was statistically higher than for the controls. The authors raise the question of the need for further comprehensive investigations of the established effects of the hypogeomagnetic environment."} {"id": "PMID:162140", "title": "Occupational dermatitis artefacta.", "content": "Nine cases of disease malingering with skin lesions attributed by the patients to occupational factors are reported. History and morphology of the lesions provided sufficient grounds for the diagnosis of occupational dermatitis arterfacta. Four out of nine patients admitted to having produced these artefacts.", "contents": "Occupational dermatitis artefacta. Nine cases of disease malingering with skin lesions attributed by the patients to occupational factors are reported. History and morphology of the lesions provided sufficient grounds for the diagnosis of occupational dermatitis arterfacta. Four out of nine patients admitted to having produced these artefacts."} {"id": "PMID:162141", "title": "Dermatoses of the neck affecting violin and viola players (\"fiddler's neck\", and contact dermatitis).", "content": "Skin lesions occurring on the neck of violin or viola players are described, in the light of two personal observations. The lesions can be divided into two types: 1. Lesions described as \"fiddler's neck\", i.e. an area of erythematous, sometimes pigmented or scaly lichenification on the left side of the neck, just below the angle of the jaw, where the chin rest of the instrument is in contact with the skin. Histopathologic features of the lesions are described. 2. Allergic contact dermatitis to wooden or metallic parts of the violin. The recent literature is reviewed.", "contents": "Dermatoses of the neck affecting violin and viola players (\"fiddler's neck\", and contact dermatitis). Skin lesions occurring on the neck of violin or viola players are described, in the light of two personal observations. The lesions can be divided into two types: 1. Lesions described as \"fiddler's neck\", i.e. an area of erythematous, sometimes pigmented or scaly lichenification on the left side of the neck, just below the angle of the jaw, where the chin rest of the instrument is in contact with the skin. Histopathologic features of the lesions are described. 2. Allergic contact dermatitis to wooden or metallic parts of the violin. The recent literature is reviewed."} {"id": "PMID:162142", "title": "[Occupational allergy to diazo-paper used in the textile industry (author's transl)].", "content": "A worker of the textile industry showed an allergic contact eczema caused by diazodiethylaniline contained in diazopaper used in the manufacture of patterns.", "contents": "[Occupational allergy to diazo-paper used in the textile industry (author's transl)]. A worker of the textile industry showed an allergic contact eczema caused by diazodiethylaniline contained in diazopaper used in the manufacture of patterns."} {"id": "PMID:162143", "title": "[Positive side-effects of antibiotic and antimicrobial drugs in therapy (author's transl)].", "content": "Since about 1950 especially, dermatologists world-wide have been utilizing the positive side-effects, discovered by chance, of all groups of antibiotic and antimicrobial drugs. These drugs are used to treat certain non-microbially induced dermatoses, without any knowledge of the mechanisms involved. A short history is given and the most important drugs and the indications for their use are described. The following drugs are undoubtedly effective and sometimes even the therapy of choice: tetracyclines in acne vulgaris and rosacea (including rosacea keratitis); penicillin G in acrodermatitis atrophicans and cold urticaria; dapsone in dermatitis herpetiformis and - as a powerful adjuvant - in acne vulgaris and rosacea. Before the discovery of the socalled immunodepressive drugs, tetracycline was the only alternative to - or at least a highly effective adjuvant of - cortisone in dermatomyositis and chloroquine in localised and systemic lupus erythematosus. Finally, clioquinole was life-saving in acrodermatitis continua in children until this condition was recently identified as a zinc-deficiency syndrome. Therapeutical mechanisms have been found only in the case of acne, rosacea and dermatitis herpetiformis. In most other diseases the nature of the therapeutical effectiveness of antibiotic and antimicrobial drugs still remains a mystery.", "contents": "[Positive side-effects of antibiotic and antimicrobial drugs in therapy (author's transl)]. Since about 1950 especially, dermatologists world-wide have been utilizing the positive side-effects, discovered by chance, of all groups of antibiotic and antimicrobial drugs. These drugs are used to treat certain non-microbially induced dermatoses, without any knowledge of the mechanisms involved. A short history is given and the most important drugs and the indications for their use are described. The following drugs are undoubtedly effective and sometimes even the therapy of choice: tetracyclines in acne vulgaris and rosacea (including rosacea keratitis); penicillin G in acrodermatitis atrophicans and cold urticaria; dapsone in dermatitis herpetiformis and - as a powerful adjuvant - in acne vulgaris and rosacea. Before the discovery of the socalled immunodepressive drugs, tetracycline was the only alternative to - or at least a highly effective adjuvant of - cortisone in dermatomyositis and chloroquine in localised and systemic lupus erythematosus. Finally, clioquinole was life-saving in acrodermatitis continua in children until this condition was recently identified as a zinc-deficiency syndrome. Therapeutical mechanisms have been found only in the case of acne, rosacea and dermatitis herpetiformis. In most other diseases the nature of the therapeutical effectiveness of antibiotic and antimicrobial drugs still remains a mystery."} {"id": "PMID:162146", "title": "New insights into the old problem of chronic pelvic pain.", "content": "Between July, 1974 and February, 1979, 109 adolescent girls, ranging in age from 10 1/2 to 19 yr. with unexplained chronic pelvic pain, underwent diagnostic laparoscopy. Endometriosis was the most common finding occurring in 49 patients (45%), followed by postoperative adhesions in 17 patients (16%) and congenital abnormalities of the uterus in 10 patients (9%). Other important causes were chronic pelvic inflammatory disease with peritubal and periovarian adhesions in 9%, chronic hemoperitoneum in 5%, functional ovarian cysts in 5%, and uterine serositis in 2%. No pathology could be seen in 10 patients (9%). Analysis of the presenting symptoms and physical findings revealed in most instances that the presence of significant pelvic pathology as a cause of the chronic pelvic pain was predictable and had been previously misdiagnosed. Intraoperative and postoperative management of the major problems encountered stress the importance of conservative surgery and the need for long-term follow-up.", "contents": "New insights into the old problem of chronic pelvic pain. Between July, 1974 and February, 1979, 109 adolescent girls, ranging in age from 10 1/2 to 19 yr. with unexplained chronic pelvic pain, underwent diagnostic laparoscopy. Endometriosis was the most common finding occurring in 49 patients (45%), followed by postoperative adhesions in 17 patients (16%) and congenital abnormalities of the uterus in 10 patients (9%). Other important causes were chronic pelvic inflammatory disease with peritubal and periovarian adhesions in 9%, chronic hemoperitoneum in 5%, functional ovarian cysts in 5%, and uterine serositis in 2%. No pathology could be seen in 10 patients (9%). Analysis of the presenting symptoms and physical findings revealed in most instances that the presence of significant pelvic pathology as a cause of the chronic pelvic pain was predictable and had been previously misdiagnosed. Intraoperative and postoperative management of the major problems encountered stress the importance of conservative surgery and the need for long-term follow-up."} {"id": "PMID:162147", "title": "The efficacy of fenbendazole at a dosage rate of 7,5 mg/kg against nematode infestations in cattle.", "content": "Fenbedazole, dosed to artificially infested cattle at 7,5 mg/kg live mass, was more than 80% effective in more than 80% of the treated animals against immature and adult Haemonchus placei, Ostertagia ostertagi; Cooperia spp., Bunostomum phlebotum and Oesophagostomum radiatum.", "contents": "The efficacy of fenbendazole at a dosage rate of 7,5 mg/kg against nematode infestations in cattle. Fenbedazole, dosed to artificially infested cattle at 7,5 mg/kg live mass, was more than 80% effective in more than 80% of the treated animals against immature and adult Haemonchus placei, Ostertagia ostertagi; Cooperia spp., Bunostomum phlebotum and Oesophagostomum radiatum."} {"id": "PMID:162148", "title": "Uptake of iron by Gomphosphaeria aponina, a possible control organism for the Florida red tide Pytochodiscus brevis.", "content": "The assimilation of iron, a growth-limiting metal ion of the cytotoxic marine cyanobacterium, Gomphosphaeria aponina, has been examined in both static and steady-state cultures using 59Fe (III). Uptake of iron by cells followed first-order kinetics, and biphasic (absorption and uptake) behavior was observed as suggested by noted differences between cultures incubated in the light and in the dark. Iron removal in illuminated cultures was rapid, occurring at rates comparable to exponential growth rates. Although uptake was mediated by a chelating agent (EDTA), synthesis and iron assisted transport by hydroxamate-type siderophores was not involved in the uptake of iron by cells, as determined by standard chemical and biological assays of iron deficient cultures. The ecological implications of this research is considered with respect to the cytotoxic antagonism between the cyanobacterium and Florida's red tide organism, Pytochodiscus brevis (Gymnodinium breve).", "contents": "Uptake of iron by Gomphosphaeria aponina, a possible control organism for the Florida red tide Pytochodiscus brevis. The assimilation of iron, a growth-limiting metal ion of the cytotoxic marine cyanobacterium, Gomphosphaeria aponina, has been examined in both static and steady-state cultures using 59Fe (III). Uptake of iron by cells followed first-order kinetics, and biphasic (absorption and uptake) behavior was observed as suggested by noted differences between cultures incubated in the light and in the dark. Iron removal in illuminated cultures was rapid, occurring at rates comparable to exponential growth rates. Although uptake was mediated by a chelating agent (EDTA), synthesis and iron assisted transport by hydroxamate-type siderophores was not involved in the uptake of iron by cells, as determined by standard chemical and biological assays of iron deficient cultures. The ecological implications of this research is considered with respect to the cytotoxic antagonism between the cyanobacterium and Florida's red tide organism, Pytochodiscus brevis (Gymnodinium breve)."} {"id": "PMID:162151", "title": "Cell-mediated immunity to Theileria-transformed cell lines.", "content": "In East and Central Africa the protozoan parasite Theileria parva causes a disease of cattle called East Coast fever (ECF). In Kenya alone between 60,000 and 85,000 cattle die from ECF every year. Infected animals can recover from ECF either naturally or after treatment with tetracyclines or menoctone and are subsequently able to resist challenge with the homologous strain of parasite. That this acquired resistance is due to cell-mediated rather than humoral immunity has been suspected but never decisively shown. A major difficulty in studying immunity to ECF has been the lack of inbred animals for studying Theileria-specific immunity in the absence of allogeneic histocompatibility barriers. We have avoided this problem by measuring cell-mediated immune responses in a syngeneic system in vitro. Unidirectional mixed lymphocyte cultures (MLC) were set up using bovine peripheral blood lymphocytes (PBL) as responder cells and autologous cell lines transformed in vitro by T. parva as stimulator cells. In these cultures, DNA synthesis was induced in PBL from both normal and Theileria-immune animals. However, cytotoxic lymphocytes were induced only in cultures containing responder lymphocytes from Theileria-immune cattle. The results show that Theileria-transformed cells express antigens which are recognized by effector cells and provide evidence that cell-mediated cytotoxic mechanisms function in immunity to ECF.", "contents": "Cell-mediated immunity to Theileria-transformed cell lines. In East and Central Africa the protozoan parasite Theileria parva causes a disease of cattle called East Coast fever (ECF). In Kenya alone between 60,000 and 85,000 cattle die from ECF every year. Infected animals can recover from ECF either naturally or after treatment with tetracyclines or menoctone and are subsequently able to resist challenge with the homologous strain of parasite. That this acquired resistance is due to cell-mediated rather than humoral immunity has been suspected but never decisively shown. A major difficulty in studying immunity to ECF has been the lack of inbred animals for studying Theileria-specific immunity in the absence of allogeneic histocompatibility barriers. We have avoided this problem by measuring cell-mediated immune responses in a syngeneic system in vitro. Unidirectional mixed lymphocyte cultures (MLC) were set up using bovine peripheral blood lymphocytes (PBL) as responder cells and autologous cell lines transformed in vitro by T. parva as stimulator cells. In these cultures, DNA synthesis was induced in PBL from both normal and Theileria-immune animals. However, cytotoxic lymphocytes were induced only in cultures containing responder lymphocytes from Theileria-immune cattle. The results show that Theileria-transformed cells express antigens which are recognized by effector cells and provide evidence that cell-mediated cytotoxic mechanisms function in immunity to ECF."} {"id": "PMID:162173", "title": "Study of the effects of a long acting injectable-progesterone on the ovarian and uterine histomorphology of the androgenised female rats of Long-Evans strain.", "content": "The study was aimed at determining the possible role of long acting progesterone-DMPA in effecting reversal of the effect of TP on neonatally treated female Long-Evans rats. Five day-old female litters injected with 1.25 mg. TP went into persistent estrous on attaining maturity. DMPA when given in proper dosage and time reverted the condition.", "contents": "Study of the effects of a long acting injectable-progesterone on the ovarian and uterine histomorphology of the androgenised female rats of Long-Evans strain. The study was aimed at determining the possible role of long acting progesterone-DMPA in effecting reversal of the effect of TP on neonatally treated female Long-Evans rats. Five day-old female litters injected with 1.25 mg. TP went into persistent estrous on attaining maturity. DMPA when given in proper dosage and time reverted the condition."} {"id": "PMID:162174", "title": "[Effect of calusterone on the stem cell compartment after suppression with busulfan in mice].", "content": "These studies were undertaken to evaluate the effect of Calusterone (a weakly androgenic steroid) on hemopoiesis in mice. Cellular proliferation was suppressed by a single (IP) injection of busulfan (BU) (40 mg/Kg). Calusterone (CA) was administered s.c. SC daily (10 mg/Kg); controls received an equivalent injection of oil vehicle. Hemopoiesis was characterized by measurement of peripheral blood neutrophils, bone marrow cellularity, differentials and stem cell content. This included pluripotent (CFU-S), granulocytic (CFU-C) and erythroid (CFU-E) progenitor cells. Only a minimal decrease in narrow cellularity was observed after busulfan; similar values were obtained in calusterone recipients. Neutrophils fell by day 4, showed an abortive rise on day 8 and subsequently fell to 32% of control values. Calusterone recipients showed a 2 fold higher value (62%) on day 12. CFU-S, CFU-C, and CFU-E were depressed to 20-40% of control values by day 2 after busulfan. Although CFU-S and CFU-C remained depressed through the 14th day, CFU-E recovered by day 8 CA stimulated an overshoot in these cells to 288% of control values. These findings correlated with an increase in marrow erythroid cells to 182% on day 10. CFU-S remained low (20%) by day 14 and gradually increased to 50% of control by day 24. A delayed 10 day course of CA more than doubled the CFU-S recovery. These findings show that BU markedly suppress hemopoietic stem cells: a differential recovery is noted between CFU-E and the other progenitor cells. CA increase the recovery of all 3 hemopoietic stem cell compartments when given either immediately or in a delayed schedule. This suggests that this compound may be of use in the therapy of bone marrow hypoplasia.", "contents": "[Effect of calusterone on the stem cell compartment after suppression with busulfan in mice]. These studies were undertaken to evaluate the effect of Calusterone (a weakly androgenic steroid) on hemopoiesis in mice. Cellular proliferation was suppressed by a single (IP) injection of busulfan (BU) (40 mg/Kg). Calusterone (CA) was administered s.c. SC daily (10 mg/Kg); controls received an equivalent injection of oil vehicle. Hemopoiesis was characterized by measurement of peripheral blood neutrophils, bone marrow cellularity, differentials and stem cell content. This included pluripotent (CFU-S), granulocytic (CFU-C) and erythroid (CFU-E) progenitor cells. Only a minimal decrease in narrow cellularity was observed after busulfan; similar values were obtained in calusterone recipients. Neutrophils fell by day 4, showed an abortive rise on day 8 and subsequently fell to 32% of control values. Calusterone recipients showed a 2 fold higher value (62%) on day 12. CFU-S, CFU-C, and CFU-E were depressed to 20-40% of control values by day 2 after busulfan. Although CFU-S and CFU-C remained depressed through the 14th day, CFU-E recovered by day 8 CA stimulated an overshoot in these cells to 288% of control values. These findings correlated with an increase in marrow erythroid cells to 182% on day 10. CFU-S remained low (20%) by day 14 and gradually increased to 50% of control by day 24. A delayed 10 day course of CA more than doubled the CFU-S recovery. These findings show that BU markedly suppress hemopoietic stem cells: a differential recovery is noted between CFU-E and the other progenitor cells. CA increase the recovery of all 3 hemopoietic stem cell compartments when given either immediately or in a delayed schedule. This suggests that this compound may be of use in the therapy of bone marrow hypoplasia."} {"id": "PMID:162175", "title": "[Catamnestic study of 92 cases of burned patients: medico-legal considerations].", "content": "The authors have examined 1478 burned or scalded patients of the Plastic Surgery Institute of the University of Parma from 1967 to 1976; they have considered particularly 92 cases who showed more than 20% of burned skin. For these patients they have considered many data of medico-legal interest in order to facilitate the estimate of the personal damage in penal and civil law.", "contents": "[Catamnestic study of 92 cases of burned patients: medico-legal considerations]. The authors have examined 1478 burned or scalded patients of the Plastic Surgery Institute of the University of Parma from 1967 to 1976; they have considered particularly 92 cases who showed more than 20% of burned skin. For these patients they have considered many data of medico-legal interest in order to facilitate the estimate of the personal damage in penal and civil law."} {"id": "PMID:162176", "title": "Qualitative estimation of blood velocity changes in human umbilical arteries after delivery.", "content": "Qualitative doppler shift ultrasound estimations of blood velocity were made from umbilical arteries of 17 neonates for 90 sec after delivery using a 10 MHz doppler instrument. The mean maximum doppler shift frequency at 10 sec was 1.5 kHz +/- 0.3 (SE) reducing to 0.5 +/- 0.1 kHz at 60 sec after delivery. This indicates that flow velocity cannot be quantified. The initial mean pulsatility index was 10.6 suggesting that either constrictions were occurring in the arteries by 10 sec after delivery or that the placenta has a high impedance or both.", "contents": "Qualitative estimation of blood velocity changes in human umbilical arteries after delivery. Qualitative doppler shift ultrasound estimations of blood velocity were made from umbilical arteries of 17 neonates for 90 sec after delivery using a 10 MHz doppler instrument. The mean maximum doppler shift frequency at 10 sec was 1.5 kHz +/- 0.3 (SE) reducing to 0.5 +/- 0.1 kHz at 60 sec after delivery. This indicates that flow velocity cannot be quantified. The initial mean pulsatility index was 10.6 suggesting that either constrictions were occurring in the arteries by 10 sec after delivery or that the placenta has a high impedance or both."} {"id": "PMID:162179", "title": "Some neuroendocrine parameters in bipolar and unipolar depression.", "content": "There is mounting evidence showing that some pituitary and hypothalamic hormones play an important role in the affective disorders and may directly affect brain function and behavior. This report briefly reviews some recent endocrinological studies in affective illness with special reference to bipolar and unipolar form of illness. Data on prolactin and growth hormone response to levodopa in bipolar and unipolar illness presented. Preliminary data on plasma dopamine beta hydroxylase activity measured over a 24-h period are illustrated in patients suffering from bipolar and unipolar illnesses as compared to controls. The significance of these results is discussed in relation to biogenic amine dysfunction in the major affective disorders.", "contents": "Some neuroendocrine parameters in bipolar and unipolar depression. There is mounting evidence showing that some pituitary and hypothalamic hormones play an important role in the affective disorders and may directly affect brain function and behavior. This report briefly reviews some recent endocrinological studies in affective illness with special reference to bipolar and unipolar form of illness. Data on prolactin and growth hormone response to levodopa in bipolar and unipolar illness presented. Preliminary data on plasma dopamine beta hydroxylase activity measured over a 24-h period are illustrated in patients suffering from bipolar and unipolar illnesses as compared to controls. The significance of these results is discussed in relation to biogenic amine dysfunction in the major affective disorders."} {"id": "PMID:162180", "title": "Should 'non-Feighner schizophrenia' be classified with affective disorder?", "content": "Narrow definitions of schizophrenia increase homogeneity at the expense of leaving unclassified many patients with shizophrenic symptoms. Family history and follow-up studies indicate that many such patients ought to be classified with those having affective disorders. This study determines morbid risks for affective disorder and schizophrenia in first degree relatives of patients with chart but not research diagnoses of schizophrenia. Comparisons with morbid risk figures for relatives of individuals satisfying research criteria for depression, mania or schizophrenia indicate that the 'non-Feighner schizophrenia' group is probably too heterogenous to be classified entirely as affective disorder or as schizophrenia.", "contents": "Should 'non-Feighner schizophrenia' be classified with affective disorder? Narrow definitions of schizophrenia increase homogeneity at the expense of leaving unclassified many patients with shizophrenic symptoms. Family history and follow-up studies indicate that many such patients ought to be classified with those having affective disorders. This study determines morbid risks for affective disorder and schizophrenia in first degree relatives of patients with chart but not research diagnoses of schizophrenia. Comparisons with morbid risk figures for relatives of individuals satisfying research criteria for depression, mania or schizophrenia indicate that the 'non-Feighner schizophrenia' group is probably too heterogenous to be classified entirely as affective disorder or as schizophrenia."} {"id": "PMID:162181", "title": "Appropriateness of drugs prescribed by primary care physicians for depressed outpatients.", "content": "In a sample of middle class individuals seeking martial and sexual counseling, 30% had diagnosable psychiatric illness, including 14% who had depressions at the time of interview. Those with psychiatric syndromes were significantly more likely to have prescribed psychoactive than those without these syndromes. Those with depression were more likely to have received diazepam and similar drugs than antidepressants. The same was true for those with other syndromes but in many of these cases, diazepam or other antianxiety agents seemed more appropriate. Thus, affective disorder might well be the psychiatric syndrome for which these drugs are most often inappropriately prescribed. Inappropriate treatment is a matter of concern in an illness which is potentially fatal.", "contents": "Appropriateness of drugs prescribed by primary care physicians for depressed outpatients. In a sample of middle class individuals seeking martial and sexual counseling, 30% had diagnosable psychiatric illness, including 14% who had depressions at the time of interview. Those with psychiatric syndromes were significantly more likely to have prescribed psychoactive than those without these syndromes. Those with depression were more likely to have received diazepam and similar drugs than antidepressants. The same was true for those with other syndromes but in many of these cases, diazepam or other antianxiety agents seemed more appropriate. Thus, affective disorder might well be the psychiatric syndrome for which these drugs are most often inappropriately prescribed. Inappropriate treatment is a matter of concern in an illness which is potentially fatal."} {"id": "PMID:162182", "title": "Unipolar mania revisited.", "content": "In a more sophisticated replication of an earlier study (Abrams and Taylor 1974), we examined 77 manic patients, of whom 29 had never suffered a depressive illness, and had two or more manic attacks. These unipolar manics were similar to the 48 bipolar manics for a wide variety of clinical, phenomenological, historical, laboratory and demographic variables, generally supporting our earlier findings. However, the present sample showed a striking excess of males among the unipolar manics, as well as an increased morbid risk for unipolar depression in first-degree relatives. Although not readily explainable, these differences suggest that it is premature to equate unipolar mania with classical bipolar illness. Further studies of unipolar mania are in progress.", "contents": "Unipolar mania revisited. In a more sophisticated replication of an earlier study (Abrams and Taylor 1974), we examined 77 manic patients, of whom 29 had never suffered a depressive illness, and had two or more manic attacks. These unipolar manics were similar to the 48 bipolar manics for a wide variety of clinical, phenomenological, historical, laboratory and demographic variables, generally supporting our earlier findings. However, the present sample showed a striking excess of males among the unipolar manics, as well as an increased morbid risk for unipolar depression in first-degree relatives. Although not readily explainable, these differences suggest that it is premature to equate unipolar mania with classical bipolar illness. Further studies of unipolar mania are in progress."} {"id": "PMID:162183", "title": "Free and total plasma tryptophan in endogenous depression.", "content": "The free and total plasma tryptophan concentrations were measured in 41 female depressive. Fifteen patients were subsequently treated with L-tryptophan. The free and total tryptophan were normal in the drug-free depressives and in the depressives on lithium. No significant in free and total plasma tryptophan were found between unipolar and bipolar depressed subjects, or between patients who recovered from depression following L-tryptophan therapy and patients who were resistant. The results suggest that the basal free tryptophan concentration in the plasma of depressed subjects is normal. They furthermore indicate that neither free nor total plasma tryptophan concentrations are valid predictors for the course of a treatment of depressed subjects with L-tryptophan.", "contents": "Free and total plasma tryptophan in endogenous depression. The free and total plasma tryptophan concentrations were measured in 41 female depressive. Fifteen patients were subsequently treated with L-tryptophan. The free and total tryptophan were normal in the drug-free depressives and in the depressives on lithium. No significant in free and total plasma tryptophan were found between unipolar and bipolar depressed subjects, or between patients who recovered from depression following L-tryptophan therapy and patients who were resistant. The results suggest that the basal free tryptophan concentration in the plasma of depressed subjects is normal. They furthermore indicate that neither free nor total plasma tryptophan concentrations are valid predictors for the course of a treatment of depressed subjects with L-tryptophan."} {"id": "PMID:162184", "title": "The Hopkins Symptom Checklist (HSCL)--factors derived from the HSCL-90.", "content": "A factor analysis of the 90-item version of the Hopkins Symptom Checklist, performed on the pretreatment self-ratings of nonpsychotic outpatients with symptoms of depression and anxiety, revealed the presence of 8 clinically meaningful factors. These eight orthogonal factors each contained at least 5 items with loadings above 0.40 and explained 4.5% or more of the matrix variance. They were labeled Somatization, Phobic-Anxiety, Retarded Depression, Agitated Depression, Obsessive-Compulsive, Interpersonal Sensitivity, Anger-Hostility and Psychoticism.", "contents": "The Hopkins Symptom Checklist (HSCL)--factors derived from the HSCL-90. A factor analysis of the 90-item version of the Hopkins Symptom Checklist, performed on the pretreatment self-ratings of nonpsychotic outpatients with symptoms of depression and anxiety, revealed the presence of 8 clinically meaningful factors. These eight orthogonal factors each contained at least 5 items with loadings above 0.40 and explained 4.5% or more of the matrix variance. They were labeled Somatization, Phobic-Anxiety, Retarded Depression, Agitated Depression, Obsessive-Compulsive, Interpersonal Sensitivity, Anger-Hostility and Psychoticism."} {"id": "PMID:162186", "title": "A Doppler ultrasound technique for measuring human milk flow.", "content": "The authors describe the development of a Doppler ultrasound flow transducer used in conjunction with a zero-crossing demodulator for breast milk flow measurement. The results of the preliminary evaluation in vitro are presented in the paper. The design is at present being minaturised in order to use the transducer for in vivo measurement.", "contents": "A Doppler ultrasound technique for measuring human milk flow. The authors describe the development of a Doppler ultrasound flow transducer used in conjunction with a zero-crossing demodulator for breast milk flow measurement. The results of the preliminary evaluation in vitro are presented in the paper. The design is at present being minaturised in order to use the transducer for in vivo measurement."} {"id": "PMID:162187", "title": "A maximum frequency detector for Doppler blood velocimeters.", "content": "The clinical information available from ultrasonic Doppler blood velocimeters may be analysed in several ways, spectral analysis probably being the best. This is, however, a relatively expensive technique when compared with the cost of commerically available Doppler velocimeters. A large part of the diagnostic information present can be obtained from the maximum blood velocity in the vessel at any one time. A relatively inexpensive analogue method of extracting this information from the Doppler signal is described, and the preliminary results obtained on signals derived from peripheral arteries are discussed.", "contents": "A maximum frequency detector for Doppler blood velocimeters. The clinical information available from ultrasonic Doppler blood velocimeters may be analysed in several ways, spectral analysis probably being the best. This is, however, a relatively expensive technique when compared with the cost of commerically available Doppler velocimeters. A large part of the diagnostic information present can be obtained from the maximum blood velocity in the vessel at any one time. A relatively inexpensive analogue method of extracting this information from the Doppler signal is described, and the preliminary results obtained on signals derived from peripheral arteries are discussed."} {"id": "PMID:162190", "title": "In vitro inhibition of human lymphocyte transformation by natural or synthetic prostaglandins.", "content": "We have examined the role of 45 natural or synthetic prostaglandins (PGs) in the in vitro responsiveness of human lymphocytes toward two different varieties of mitogenic stimuli: the mixed lymphocyte culture (MLC) and the tuberculinic test (LTT). Addition of PGs to culture of lymphocytes decreases the uptake of 3H thymidin.", "contents": "In vitro inhibition of human lymphocyte transformation by natural or synthetic prostaglandins. We have examined the role of 45 natural or synthetic prostaglandins (PGs) in the in vitro responsiveness of human lymphocytes toward two different varieties of mitogenic stimuli: the mixed lymphocyte culture (MLC) and the tuberculinic test (LTT). Addition of PGs to culture of lymphocytes decreases the uptake of 3H thymidin."} {"id": "PMID:162185", "title": "Suppression of murine allogeneic cell interactions by sex hormones.", "content": "Investigations have been carried out on the action of several steroid hormones on lymphocyte functions in inbred strains of mice. The recognitive, proliferative and effector phases of allogeneic cell interactions in vitro were assessed using a mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML). In MLR containing Balb/c (responder) and C57bl/6 (stimulator) splenocytes DNA synthesis was markedly reduced in the presence of progesterone, cortisol or estradiol. In CML, progesterone and estradiol (1-5 microgram/ml) blocked in vitro generation of cytotoxic lymphocytes, while cultures with cortisol were partially inhibited. None of these hormones suppressed the cytotoxic activity of previously sensitized effector cells generated in vitro. Cultures containing testosterone expressed both normal DNA synthesis in MLR and cytotoxic activity in the CML test. These findings suggest a selective pattern of immunosuppression by sex hormones which may be important in preventing graft rejection or graft-versus-host interactions which may arise as a consequence of fetal engraftment during pregnancy.", "contents": "Suppression of murine allogeneic cell interactions by sex hormones. Investigations have been carried out on the action of several steroid hormones on lymphocyte functions in inbred strains of mice. The recognitive, proliferative and effector phases of allogeneic cell interactions in vitro were assessed using a mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML). In MLR containing Balb/c (responder) and C57bl/6 (stimulator) splenocytes DNA synthesis was markedly reduced in the presence of progesterone, cortisol or estradiol. In CML, progesterone and estradiol (1-5 microgram/ml) blocked in vitro generation of cytotoxic lymphocytes, while cultures with cortisol were partially inhibited. None of these hormones suppressed the cytotoxic activity of previously sensitized effector cells generated in vitro. Cultures containing testosterone expressed both normal DNA synthesis in MLR and cytotoxic activity in the CML test. These findings suggest a selective pattern of immunosuppression by sex hormones which may be important in preventing graft rejection or graft-versus-host interactions which may arise as a consequence of fetal engraftment during pregnancy."} {"id": "PMID:162192", "title": "[Function studies of an atropine derivative--ipratropium bromide in an aerosol device--in patients with chronic obstructive bronchopneumopathies].", "content": "Ipratropium exerted marked bronchodilating effects in 22 patients with chronic obstructive lung diseases. The tolerance of the drug was excellent. In long-term treatment the patients do not get accustomed to the drug.", "contents": "[Function studies of an atropine derivative--ipratropium bromide in an aerosol device--in patients with chronic obstructive bronchopneumopathies]. Ipratropium exerted marked bronchodilating effects in 22 patients with chronic obstructive lung diseases. The tolerance of the drug was excellent. In long-term treatment the patients do not get accustomed to the drug."} {"id": "PMID:162194", "title": "Immune responsiveness of patients with autoimmune diseases and immunodeficiency.", "content": "Assessment of immune reactivity of patients with disorders of immunopathological origin requires a well-equipped clinical laboratory. The complex mechanism of immune reactions cannot be studied by simple techniques, although the most sophisticated methods do not often prove more reliable than simpler ones. While humoral immune reactivity can be measured by determining serum immunoglobulin levels, the assessment of cellular reactivity requires more complex methods; for this purpose lymphocyte marker studies, mitogen induced blast transformation, LIF production, and skin reactivity proved to be the methods of choice.", "contents": "Immune responsiveness of patients with autoimmune diseases and immunodeficiency. Assessment of immune reactivity of patients with disorders of immunopathological origin requires a well-equipped clinical laboratory. The complex mechanism of immune reactions cannot be studied by simple techniques, although the most sophisticated methods do not often prove more reliable than simpler ones. While humoral immune reactivity can be measured by determining serum immunoglobulin levels, the assessment of cellular reactivity requires more complex methods; for this purpose lymphocyte marker studies, mitogen induced blast transformation, LIF production, and skin reactivity proved to be the methods of choice."} {"id": "PMID:162195", "title": "Histamine-binding receptors and Fc receptors of T lymphocytes in SLE.", "content": "The participation of TG cells forming the suppressor T cell population and of histamine-binding cells was determined in the peripheral blood of patients with SLE. Former was considerably diminished in the active phase of the disease, latter was found diminished in both the active and the inactive phase. The results published in this paper support the functional disorder of suppressor T cells in SLE, an assumption based only on sporadic data before.", "contents": "Histamine-binding receptors and Fc receptors of T lymphocytes in SLE. The participation of TG cells forming the suppressor T cell population and of histamine-binding cells was determined in the peripheral blood of patients with SLE. Former was considerably diminished in the active phase of the disease, latter was found diminished in both the active and the inactive phase. The results published in this paper support the functional disorder of suppressor T cells in SLE, an assumption based only on sporadic data before."} {"id": "PMID:162221", "title": "[Histological localization of hydrolases in the epididymis of the dog].", "content": "Localization and activity of five hydrolases (alkaline phosphatase, adenosine triphosphatase, acid phosphatase, nonspecific esterase and leucylamino-peptidase) were evaluated histochemically in the epididymides of mature dogs. In the ductuli efferentes, cilia and apical parts of the epithelial cells displayed high activity of alkaline phosphatase and adenosine triphosphatase. Strong activity of acid phosphatase, nonspecific esterase and leucylamino-peptidase was present in the basal and supranuclear zones of the epithelium of the ductuli efferentes. Stereocilia of all three segments of the ductus epididymidis showed a high activity of alkaline phosphatase. Positive adenosine triphosphatase reaction was confined to the stereocilia of the initial segment. A complex pattern of acid phosphatase activity was observed in the middle segment. The subdivision of the middle segment in four subsegments was therefore suggested. In the epithelium of the initial segment only a few nonspecific esterase-positive cells were seen. The infranuclear and basal areas of the epithelium in the middle segment and the supranuclear zone of the terminal segment displayed distinct nonspecific esterase activity. The possible contribution of the hydrolases to the function of the epididymis is discussed.", "contents": "[Histological localization of hydrolases in the epididymis of the dog]. Localization and activity of five hydrolases (alkaline phosphatase, adenosine triphosphatase, acid phosphatase, nonspecific esterase and leucylamino-peptidase) were evaluated histochemically in the epididymides of mature dogs. In the ductuli efferentes, cilia and apical parts of the epithelial cells displayed high activity of alkaline phosphatase and adenosine triphosphatase. Strong activity of acid phosphatase, nonspecific esterase and leucylamino-peptidase was present in the basal and supranuclear zones of the epithelium of the ductuli efferentes. Stereocilia of all three segments of the ductus epididymidis showed a high activity of alkaline phosphatase. Positive adenosine triphosphatase reaction was confined to the stereocilia of the initial segment. A complex pattern of acid phosphatase activity was observed in the middle segment. The subdivision of the middle segment in four subsegments was therefore suggested. In the epithelium of the initial segment only a few nonspecific esterase-positive cells were seen. The infranuclear and basal areas of the epithelium in the middle segment and the supranuclear zone of the terminal segment displayed distinct nonspecific esterase activity. The possible contribution of the hydrolases to the function of the epididymis is discussed."} {"id": "PMID:162222", "title": "Auto-reaction phenomenon detected by enzyme electrosyneresis in the serum of patients with viral hepatitis and other diseases with immune complexes.", "content": "The use of modified electrosyneresis by making 760 sera of healthy persons or persons suffering from various diseases with immune complexes to react with their own pronase-treated serum has shown the following results: - One of 220 sera of healthy persons, 11 were positive in ESE (5%); - Out of 123 sera of HBsAg carriers, 23 were positive (18.6%); - Out of 135 sera of patients with acute viral type B hepatitis, 132 were positive (97.7%); - Out of 168 sera of patients with acute HBsAg negative hepatitis, 127 were positive (75.5%); - 4 cases of fulminant hepatitis were all strongly positive; - 54 cases of patients with rheumatoid arthritis were 100% positive; - 2 cases of patients with systemic lupus erythematosus were positive; - Out of 6 patients with glomerulonephritis 3 were positive; - Out of 34 patients with carcinoma of various organs, 19 were positive (55.88%). The Authors believe, on the basis of the research work set forth partly in the present report, that this interaction is connected with the presence of immune complexes. The method used has been called Enzyme Electrosyneresis (ESE) and the detected antigen \"Auto antigen exposed by protease and by electrosyneresis\" (AEPE).", "contents": "Auto-reaction phenomenon detected by enzyme electrosyneresis in the serum of patients with viral hepatitis and other diseases with immune complexes. The use of modified electrosyneresis by making 760 sera of healthy persons or persons suffering from various diseases with immune complexes to react with their own pronase-treated serum has shown the following results: - One of 220 sera of healthy persons, 11 were positive in ESE (5%); - Out of 123 sera of HBsAg carriers, 23 were positive (18.6%); - Out of 135 sera of patients with acute viral type B hepatitis, 132 were positive (97.7%); - Out of 168 sera of patients with acute HBsAg negative hepatitis, 127 were positive (75.5%); - 4 cases of fulminant hepatitis were all strongly positive; - 54 cases of patients with rheumatoid arthritis were 100% positive; - 2 cases of patients with systemic lupus erythematosus were positive; - Out of 6 patients with glomerulonephritis 3 were positive; - Out of 34 patients with carcinoma of various organs, 19 were positive (55.88%). The Authors believe, on the basis of the research work set forth partly in the present report, that this interaction is connected with the presence of immune complexes. The method used has been called Enzyme Electrosyneresis (ESE) and the detected antigen \"Auto antigen exposed by protease and by electrosyneresis\" (AEPE)."} {"id": "PMID:162223", "title": "Increase in the percentage of sIgD-bearing lymphocytes during human mixed lymphocyte reaction.", "content": "In human one-way mixed lymphocyte reactions we have observed an increase in the percentage of sIgD bearing lymphocytes, detected by direct membrane immunofluorescent staining. This increase does not seem to be attributable either to the synthesis of sIgD receptor molecules by previously negative T or null cells or to a non specific stimulation of B cells by a factor released in the course of the MLR.", "contents": "Increase in the percentage of sIgD-bearing lymphocytes during human mixed lymphocyte reaction. In human one-way mixed lymphocyte reactions we have observed an increase in the percentage of sIgD bearing lymphocytes, detected by direct membrane immunofluorescent staining. This increase does not seem to be attributable either to the synthesis of sIgD receptor molecules by previously negative T or null cells or to a non specific stimulation of B cells by a factor released in the course of the MLR."} {"id": "PMID:162226", "title": "Effects of the bioreductive alkylating agent 2,3-bis(chloromethyl)-1,4-naphthoquinone on coupled mitochondria isolated from sarcoma 180 ascites cells.", "content": "The effect of CMNQ was studied on mitochondria isolated from S-180 ascites tumor cells. It was found that the primary metabolic event upon addition of CMNQ to S-180 mitochondria was a stimulation of oxygen uptake. The oxygen utilization rate was maximized at about 50 nmoles CMNQ/mg protein; at doses higher than this, inhibition of respiration was observed relative to the stimulation of respiration produced by CCCP. It was also up to 50 nmoles CMNQ/mg protein. S-180 ATPase activity is stimulated maximally by 125 nmoles CMNQ/mg protein; at doses higher than this, slight inhibition of the ATPase activity relative to the stimulation produced by CCCP is seen. In vivo treatment of CMNQ to tumor bearing animals leads to a significant reduction of in vitro S-180 cellular respiration rates. The data presented in this work coupled with previously published reports involving CMNQ support the proposal for a mitochondrial level of action for this bioreductive alkylating antineoplastic agent.", "contents": "Effects of the bioreductive alkylating agent 2,3-bis(chloromethyl)-1,4-naphthoquinone on coupled mitochondria isolated from sarcoma 180 ascites cells. The effect of CMNQ was studied on mitochondria isolated from S-180 ascites tumor cells. It was found that the primary metabolic event upon addition of CMNQ to S-180 mitochondria was a stimulation of oxygen uptake. The oxygen utilization rate was maximized at about 50 nmoles CMNQ/mg protein; at doses higher than this, inhibition of respiration was observed relative to the stimulation of respiration produced by CCCP. It was also up to 50 nmoles CMNQ/mg protein. S-180 ATPase activity is stimulated maximally by 125 nmoles CMNQ/mg protein; at doses higher than this, slight inhibition of the ATPase activity relative to the stimulation produced by CCCP is seen. In vivo treatment of CMNQ to tumor bearing animals leads to a significant reduction of in vitro S-180 cellular respiration rates. The data presented in this work coupled with previously published reports involving CMNQ support the proposal for a mitochondrial level of action for this bioreductive alkylating antineoplastic agent."} {"id": "PMID:162236", "title": "Suppressive effects of chlorphenesin on lymphocyte function in mice and humans.", "content": "The immunosuppressive action of chlorphenesin was investigated in a wide variety of in vitro assays for cellular immunity in humans and mice. Chlorphenesin, at doses of 20-50 micrograms/ml, inhibited mitogenic responses of both mouse and human B and T cells. These doses did not kill cells exposed to the drug for 72 hr. Mixed lymphocyte reactions in inbred strains of mice and in unrelated humans were also inhibited at concentrations of about 50 micrograms/ml. However, the generation of cytotoxic T cells in cell-mediated lympholysis assays was not inhibited to the same degree as proliferation in mixed lymphocyte reaction and the cytotoxic potential of presensitized mouse T cells for allogeneic targets was totally unaffected. These studies suggest that chlorphenesin may have a broad spectrum of suppressive effects both on T and B cells and that the predominant inhibition of proliferative responses in these cells may reduce the expansion of clones of immunocompetent cells in vivo.", "contents": "Suppressive effects of chlorphenesin on lymphocyte function in mice and humans. The immunosuppressive action of chlorphenesin was investigated in a wide variety of in vitro assays for cellular immunity in humans and mice. Chlorphenesin, at doses of 20-50 micrograms/ml, inhibited mitogenic responses of both mouse and human B and T cells. These doses did not kill cells exposed to the drug for 72 hr. Mixed lymphocyte reactions in inbred strains of mice and in unrelated humans were also inhibited at concentrations of about 50 micrograms/ml. However, the generation of cytotoxic T cells in cell-mediated lympholysis assays was not inhibited to the same degree as proliferation in mixed lymphocyte reaction and the cytotoxic potential of presensitized mouse T cells for allogeneic targets was totally unaffected. These studies suggest that chlorphenesin may have a broad spectrum of suppressive effects both on T and B cells and that the predominant inhibition of proliferative responses in these cells may reduce the expansion of clones of immunocompetent cells in vivo."} {"id": "PMID:162237", "title": "Postnatal development of bronchus-associated lymphoid tissue (BALT) in the rat, Rattus norvegicus.", "content": "The pattern of development of bronchus-associated lymphoid tissue (BALT) in specified-pathogen-free and conventional (non-barrier maintained) rats over the initial 4 weeks of life appeared to be similar. BALT first appeared around the 2nd week of life and increased in amount over the following 2 weeks. Overlying large nodules of BALT the bronchial epithelium becomes infiltrated by lymphocytes to form a lymphoepithelium. This transformation occurs earlier in conventional rats, possibly because of the differing antigen levels to which they are exposed.", "contents": "Postnatal development of bronchus-associated lymphoid tissue (BALT) in the rat, Rattus norvegicus. The pattern of development of bronchus-associated lymphoid tissue (BALT) in specified-pathogen-free and conventional (non-barrier maintained) rats over the initial 4 weeks of life appeared to be similar. BALT first appeared around the 2nd week of life and increased in amount over the following 2 weeks. Overlying large nodules of BALT the bronchial epithelium becomes infiltrated by lymphocytes to form a lymphoepithelium. This transformation occurs earlier in conventional rats, possibly because of the differing antigen levels to which they are exposed."} {"id": "PMID:162238", "title": "Bronchus-associated lymphoid tissue (BALT) in the laboratory-bred and wild rat, Rattus norvegicus.", "content": "In juvenile wild rats, bronchus-associated lymphoid tissue (BALT) development was similar to that seen in adult specified-pathogen-free rats. In adult wild rats the BALT was widespread. In one animal infected with a mycoplasma-like organism, a region of bronchoepithelium overlying a large BALT nodule was seen, through which lymphocytes appeared able to pass to make direct contact with the bronchial lumen: the significance of this observation is discussed. There was no evidence of infection in lungs from any of the specified-pathogen-free animals, where small foci of BALT were seen.", "contents": "Bronchus-associated lymphoid tissue (BALT) in the laboratory-bred and wild rat, Rattus norvegicus. In juvenile wild rats, bronchus-associated lymphoid tissue (BALT) development was similar to that seen in adult specified-pathogen-free rats. In adult wild rats the BALT was widespread. In one animal infected with a mycoplasma-like organism, a region of bronchoepithelium overlying a large BALT nodule was seen, through which lymphocytes appeared able to pass to make direct contact with the bronchial lumen: the significance of this observation is discussed. There was no evidence of infection in lungs from any of the specified-pathogen-free animals, where small foci of BALT were seen."} {"id": "PMID:162239", "title": "Epidemiological investigation of an animal house based upon phage-typing and biotyping of Staphylococcus epidermidis.", "content": "The value of biotyping and phage-typing coagulase-negative staphylococci in the epidemiological investigation of a laboratory animal house was clearly demonstrated. In the animal rooms in which conventional bacteriological methods revealed equal bacterial contamination between a conventional unit and one housing specified-pathogen-free rodents, biotyping identified Staphylococcus cohnii as the only species in the latter, compared to S. warneri, S. hominis, S. saprophyticus. S. xylosus abd S. epidermidis as well as S. cohnii in the conventional unit. Similarly, phagetyping revealed 2 phage types in the specified-pathogen-free compared to 7 in the conventional unit. Thus biotyping and phage-typing provided evidence for the existence of a barrier between these units that had presented similar gross bacteriological findings.", "contents": "Epidemiological investigation of an animal house based upon phage-typing and biotyping of Staphylococcus epidermidis. The value of biotyping and phage-typing coagulase-negative staphylococci in the epidemiological investigation of a laboratory animal house was clearly demonstrated. In the animal rooms in which conventional bacteriological methods revealed equal bacterial contamination between a conventional unit and one housing specified-pathogen-free rodents, biotyping identified Staphylococcus cohnii as the only species in the latter, compared to S. warneri, S. hominis, S. saprophyticus. S. xylosus abd S. epidermidis as well as S. cohnii in the conventional unit. Similarly, phagetyping revealed 2 phage types in the specified-pathogen-free compared to 7 in the conventional unit. Thus biotyping and phage-typing provided evidence for the existence of a barrier between these units that had presented similar gross bacteriological findings."} {"id": "PMID:162241", "title": "[Morphological, biological and biochemical study of a new species of Bulinus (Gastropoda: Planorbidae)].", "content": "A description is given of Bulinus yemenensis, a new species from Yemen belonging to the truncatus group. B. yemenensis is morphologically and biologically differenciated from B. truncatus truncatus, from which it is also electrophoretically distinguishable on the basis of the following enzyme loci: Est-2, Est-3, Pgm-2 and 6-Pgdh among the 26 analysed.", "contents": "[Morphological, biological and biochemical study of a new species of Bulinus (Gastropoda: Planorbidae)]. A description is given of Bulinus yemenensis, a new species from Yemen belonging to the truncatus group. B. yemenensis is morphologically and biologically differenciated from B. truncatus truncatus, from which it is also electrophoretically distinguishable on the basis of the following enzyme loci: Est-2, Est-3, Pgm-2 and 6-Pgdh among the 26 analysed."} {"id": "PMID:162242", "title": "[Vascular endothelium (author's transl)].", "content": "Studies during recent years have shown the importance of the vascular endothelium in several physiological and pathological circumstances. The culture of endothelial cells has permitted the direct study of endothelial functions. The endothelium is a selective barrier between blood and tissues: the molecules cross it, according to their size, either through the intercellular junctions or through the cells by pinocytotic vesicles. The permeability is modulated by vasomotor agents and modified during endothelial regeneration, especially for the lipids. The endothelium plays a prominent part in the maintenance of the blood flow through its nonthrombogenic properties. It metabolizes circulating thrombogenic substances (arachidonic acid, adenosine diphosphate) and produces potent antiaggregating agents (prostacyclin and adenosine). It may also release a plasminogen activator promoting thrombolysis. The endothelial cells contribute to the formation of the basement membrane by synthesizing collagen and fibronectin, which are involved in platelet adhesion and aggregation to exposed subendothelium. On the other hand, the endothelium has a modulating influence on the local blood flow by producing vasoconstrictors (angiotensin II and III) and vasodilating agents (adenosine and prostacyclin). It is not necessary to elucidate the coordination of these functions and their relationship to the endothelial disorders in vascular diseases.", "contents": "[Vascular endothelium (author's transl)]. Studies during recent years have shown the importance of the vascular endothelium in several physiological and pathological circumstances. The culture of endothelial cells has permitted the direct study of endothelial functions. The endothelium is a selective barrier between blood and tissues: the molecules cross it, according to their size, either through the intercellular junctions or through the cells by pinocytotic vesicles. The permeability is modulated by vasomotor agents and modified during endothelial regeneration, especially for the lipids. The endothelium plays a prominent part in the maintenance of the blood flow through its nonthrombogenic properties. It metabolizes circulating thrombogenic substances (arachidonic acid, adenosine diphosphate) and produces potent antiaggregating agents (prostacyclin and adenosine). It may also release a plasminogen activator promoting thrombolysis. The endothelial cells contribute to the formation of the basement membrane by synthesizing collagen and fibronectin, which are involved in platelet adhesion and aggregation to exposed subendothelium. On the other hand, the endothelium has a modulating influence on the local blood flow by producing vasoconstrictors (angiotensin II and III) and vasodilating agents (adenosine and prostacyclin). It is not necessary to elucidate the coordination of these functions and their relationship to the endothelial disorders in vascular diseases."} {"id": "PMID:162243", "title": "Quantitative ultrastructural aspects of cardiac hypertrophy.", "content": "Following a transient increase in relative mitochondrial volume which lasts but a few days, cardiac hypertrophy in response to pressure- or volume-overload is characterized by a preferential growth of contractile elements resulting in a decreased mitochondria/myofibrils volume ratio. At least under some conditions, the number of mitochondria/unit area increases as does the organelles surface/volume ratio. If the functional overload persists for a long period of time, e.g. 12-15 months, relative mitochondrial volume is decreased further. Unlike the imbalance in growth of mitochondria and myofibrils, the total surface area (sarcolemma plus T-System) enlarges in proportion to the increase in cell volume. While most of the components which are altered during hypertrophy become normalized as cardiac hypertrophy regresses, the process is slower than the imbalance associated with cellular enlargement. Most models of cardiac hypertrophy differ from normal growth in that the latter is characterized by proportional growth of all cellular components. In contrast, hypertrophy associated with exercise results in proportional growth in cellular components. The idea that growth of various cellular organelles is regulated by separate mechanisms is gaining support. Both sympathectomy and noreprinephrine depletion normalize the growth of mitochondria and myofibrils, while thyroxine treatment stimulates a preferential growth of mitochondria. Current evidence, therefore, suggests that myocardial cell growth probably involves complex processes which may vary with different conditions associated with the stimulus invoking enhanced cellular enlargement.", "contents": "Quantitative ultrastructural aspects of cardiac hypertrophy. Following a transient increase in relative mitochondrial volume which lasts but a few days, cardiac hypertrophy in response to pressure- or volume-overload is characterized by a preferential growth of contractile elements resulting in a decreased mitochondria/myofibrils volume ratio. At least under some conditions, the number of mitochondria/unit area increases as does the organelles surface/volume ratio. If the functional overload persists for a long period of time, e.g. 12-15 months, relative mitochondrial volume is decreased further. Unlike the imbalance in growth of mitochondria and myofibrils, the total surface area (sarcolemma plus T-System) enlarges in proportion to the increase in cell volume. While most of the components which are altered during hypertrophy become normalized as cardiac hypertrophy regresses, the process is slower than the imbalance associated with cellular enlargement. Most models of cardiac hypertrophy differ from normal growth in that the latter is characterized by proportional growth of all cellular components. In contrast, hypertrophy associated with exercise results in proportional growth in cellular components. The idea that growth of various cellular organelles is regulated by separate mechanisms is gaining support. Both sympathectomy and noreprinephrine depletion normalize the growth of mitochondria and myofibrils, while thyroxine treatment stimulates a preferential growth of mitochondria. Current evidence, therefore, suggests that myocardial cell growth probably involves complex processes which may vary with different conditions associated with the stimulus invoking enhanced cellular enlargement."} {"id": "PMID:162244", "title": "Cellular growth of cardiac muscle after birth.", "content": "Present concepts concerning DNA synthesis in the heart have been reviewed, and a speculative theory presented involving control of DNA synthesis in the developing heart. Research describing DNA synthesis in myocytes of the weanling rat heart undergoing hypertrophy has been presented. Its possible use for testing the control theory is suggested.", "contents": "Cellular growth of cardiac muscle after birth. Present concepts concerning DNA synthesis in the heart have been reviewed, and a speculative theory presented involving control of DNA synthesis in the developing heart. Research describing DNA synthesis in myocytes of the weanling rat heart undergoing hypertrophy has been presented. Its possible use for testing the control theory is suggested."} {"id": "PMID:162246", "title": "Calcium handling by cardiac sarcoplasmic reticulum.", "content": "Over the past ten years knowledge of the biochemistry of cardiac sarcoplasmic reticulum vesicles has been considerably extended. In almost all respects the Ca2+ pump of cardiac sarcoplasmic reticulum shows striking similarities to the Ca2+ pump of skeletal muscle sarcoplasmic reticulum. On the other hand, Ca2+ release mechanisms seem to be more complex in cardiac than in skeletal sarcoplasmic reticulum. Future research undoubtedly will involve characterizing the function of the many additional proteins present in cardiac sarcoplasmic reticulum, and determining possible roles for these proteins in regulating Ca2+ uptake and Ca2+ release by these membranes.", "contents": "Calcium handling by cardiac sarcoplasmic reticulum. Over the past ten years knowledge of the biochemistry of cardiac sarcoplasmic reticulum vesicles has been considerably extended. In almost all respects the Ca2+ pump of cardiac sarcoplasmic reticulum shows striking similarities to the Ca2+ pump of skeletal muscle sarcoplasmic reticulum. On the other hand, Ca2+ release mechanisms seem to be more complex in cardiac than in skeletal sarcoplasmic reticulum. Future research undoubtedly will involve characterizing the function of the many additional proteins present in cardiac sarcoplasmic reticulum, and determining possible roles for these proteins in regulating Ca2+ uptake and Ca2+ release by these membranes."} {"id": "PMID:162248", "title": "Phosphorylation and its effects on ATPase activity of cardiac and skeletal myosins.", "content": "Myosin isolated under phosphorylation conditions, showed an additional band of phosphorylated light chain. In the case of cardiac myosin, LC2 is the phosphorylated light chain whereas in skeletal myosin, it is the 18,000 dalton component known as DTNB light chain. There are no differences in K+-EDTA and Ca2+ activated myosin ATPase of cardiac and skeletal of control and phosphorylated myosins. Our experiments showed that the rat heart and skeletal muscle myosins isolated under phosphorylating conditions exhibited high phosphate content which is associated with higher actin activated Mg2+ ATPase activity of myosin as compared to control. Control myosin phosphorylated using myosin light chain kinase and Ca2+ also showed high actin activated myosin ATPase activity. Beef heart myosin isolated in the presence of phosphate buffer, also exhibited a higher level of phosphate followed by an increase in actin activation as compared to myosin isolated in the absence of phosphate buffer. All these experimental data suggest that there is a direct relationship between actin activation and the amount of phosphate incorporated as a result of phosphorylation.", "contents": "Phosphorylation and its effects on ATPase activity of cardiac and skeletal myosins. Myosin isolated under phosphorylation conditions, showed an additional band of phosphorylated light chain. In the case of cardiac myosin, LC2 is the phosphorylated light chain whereas in skeletal myosin, it is the 18,000 dalton component known as DTNB light chain. There are no differences in K+-EDTA and Ca2+ activated myosin ATPase of cardiac and skeletal of control and phosphorylated myosins. Our experiments showed that the rat heart and skeletal muscle myosins isolated under phosphorylating conditions exhibited high phosphate content which is associated with higher actin activated Mg2+ ATPase activity of myosin as compared to control. Control myosin phosphorylated using myosin light chain kinase and Ca2+ also showed high actin activated myosin ATPase activity. Beef heart myosin isolated in the presence of phosphate buffer, also exhibited a higher level of phosphate followed by an increase in actin activation as compared to myosin isolated in the absence of phosphate buffer. All these experimental data suggest that there is a direct relationship between actin activation and the amount of phosphate incorporated as a result of phosphorylation."} {"id": "PMID:162250", "title": "Changes in transcriptional activity during myocardial hypertrophy.", "content": "We have demonstrated alterations in the composition of certain groups of nuclear no-histone proteins which could account for the changes in template activity. Further identification of the individual proteins essential for this regulation will aid us in our understanding of the mechanism of myocardial cell growth during hypertrophy. We also have demonstrated the existence of several different RNA polymerase enzymes and have characterized them. The question of de novo synthesis or activation of preexisting enzyme remains unanswered. The delay in changes in activity which we found is also of great interest and may provide information as to the mechanism of increased RNA polymerase activity. The regulation of transcription can occur by changes either in the activity of the chromatin template or in the activities of the various RNA polymerase. Our studies thus far strongly suggest that during the development of hypertrophy both regulatory mechanisms are operative. Furthermore, this appears to be a bimodal function; initially there are changes only in the template and only later do changes in enzyme activity occur. To our knowledge this is the first demonstration of this form of regulation of RNA synthesis in myocardial tissue.", "contents": "Changes in transcriptional activity during myocardial hypertrophy. We have demonstrated alterations in the composition of certain groups of nuclear no-histone proteins which could account for the changes in template activity. Further identification of the individual proteins essential for this regulation will aid us in our understanding of the mechanism of myocardial cell growth during hypertrophy. We also have demonstrated the existence of several different RNA polymerase enzymes and have characterized them. The question of de novo synthesis or activation of preexisting enzyme remains unanswered. The delay in changes in activity which we found is also of great interest and may provide information as to the mechanism of increased RNA polymerase activity. The regulation of transcription can occur by changes either in the activity of the chromatin template or in the activities of the various RNA polymerase. Our studies thus far strongly suggest that during the development of hypertrophy both regulatory mechanisms are operative. Furthermore, this appears to be a bimodal function; initially there are changes only in the template and only later do changes in enzyme activity occur. To our knowledge this is the first demonstration of this form of regulation of RNA synthesis in myocardial tissue."} {"id": "PMID:162251", "title": "Limiting dilution analysis of alloantigen-reactive T lymphocytes. II. Effect of cortisone and cyclophosphamide on cytolytic T lymphocyte precursor frequencies in the thymus.", "content": "A minimal estimate of the frequency of cytolytic T lymphocyte precursors (CTL-P) in the thymus was determined by application of Poisson statistics to limiting dilution analysis. A mean CTL-P frequency of 1/1467 was obtained for C57BL/6 (H-2b) thymus cells activated by DBA/2 (H-2d) irradiated spleen cells and assayed against P-815 mastocytoma (H-2d) target cells. CTL-P frequencies were also obtained for spleen, nylon wool column purified spleen, peripheral blood, and lymph node cell populations. The effect of in vivo drug treatments on CTL-P frequencies was then examined. Cortisone at 100 mg/kg dramatically increased the CTL-P frequency in thymus by more than 20-fold despite a drastic reduction in the number of total thymus cells. The same cortisone treatment did not affect the CTL-P frequency in spleen. In contrast, cyclophosphamide at 300 mg/kg decreased the CTL-P frequency in spleen by more than 10-fold without affecting that in thymus. Cyclophosphamide at 100 mg/kg did not produce any significant change. A detailed explanation of the calculation of CTL-P frequencies is provided and their validity is discussed.", "contents": "Limiting dilution analysis of alloantigen-reactive T lymphocytes. II. Effect of cortisone and cyclophosphamide on cytolytic T lymphocyte precursor frequencies in the thymus. A minimal estimate of the frequency of cytolytic T lymphocyte precursors (CTL-P) in the thymus was determined by application of Poisson statistics to limiting dilution analysis. A mean CTL-P frequency of 1/1467 was obtained for C57BL/6 (H-2b) thymus cells activated by DBA/2 (H-2d) irradiated spleen cells and assayed against P-815 mastocytoma (H-2d) target cells. CTL-P frequencies were also obtained for spleen, nylon wool column purified spleen, peripheral blood, and lymph node cell populations. The effect of in vivo drug treatments on CTL-P frequencies was then examined. Cortisone at 100 mg/kg dramatically increased the CTL-P frequency in thymus by more than 20-fold despite a drastic reduction in the number of total thymus cells. The same cortisone treatment did not affect the CTL-P frequency in spleen. In contrast, cyclophosphamide at 300 mg/kg decreased the CTL-P frequency in spleen by more than 10-fold without affecting that in thymus. Cyclophosphamide at 100 mg/kg did not produce any significant change. A detailed explanation of the calculation of CTL-P frequencies is provided and their validity is discussed."} {"id": "PMID:162260", "title": "Localization of deoxyribonucleic acid-stimulated adenosine triphosphatases in human lymphocytes.", "content": "Two enzymes hydrolyzing ATP (ATPase A and ATPase B) were purified from freshly isolated lymphocytes of human tonsils. Both enzymes are stimulated by single-stranded DNA and seem to be localized in the chromatin. ATPase A and ATPase B appear to be distinct enzymes as judged from their elution profiles obtained after DEAE-cellulose and ATP-Sepharose column chromatography, from their behavior towards actinomycin D, a DNA intercalating agent, and from their sensitivity to monovalent salt concentration.", "contents": "Localization of deoxyribonucleic acid-stimulated adenosine triphosphatases in human lymphocytes. Two enzymes hydrolyzing ATP (ATPase A and ATPase B) were purified from freshly isolated lymphocytes of human tonsils. Both enzymes are stimulated by single-stranded DNA and seem to be localized in the chromatin. ATPase A and ATPase B appear to be distinct enzymes as judged from their elution profiles obtained after DEAE-cellulose and ATP-Sepharose column chromatography, from their behavior towards actinomycin D, a DNA intercalating agent, and from their sensitivity to monovalent salt concentration."} {"id": "PMID:162261", "title": "Kinetic study of the inhibition of myosin ATPase activity by ADP.", "content": "The kinetic parameters of the inhibition of monovalent cation activated myosin ATPase by ADP were investigated. The inhibitor constant (KI) was 1.65 X 10(-4) M and the maximal velocity (V) was 1.28 mumol Pi/mg myosin/min in the presence of 0.3M Kcl at 20 degrees C. The dependence of 1/VO on inhibitor concentration and the pH dependence of KI and Km (i.e. pKi approximately equal to pKm) show that the inhibition has a pure competitive character. The results are supported by energetic parameters, too. The enthalpy of the formation of (EI) complex was calculated. Similar results were obtained also in the presence of Rb+ activated myosin ATPase and subfragment-I K+ ATPase.", "contents": "Kinetic study of the inhibition of myosin ATPase activity by ADP. The kinetic parameters of the inhibition of monovalent cation activated myosin ATPase by ADP were investigated. The inhibitor constant (KI) was 1.65 X 10(-4) M and the maximal velocity (V) was 1.28 mumol Pi/mg myosin/min in the presence of 0.3M Kcl at 20 degrees C. The dependence of 1/VO on inhibitor concentration and the pH dependence of KI and Km (i.e. pKi approximately equal to pKm) show that the inhibition has a pure competitive character. The results are supported by energetic parameters, too. The enthalpy of the formation of (EI) complex was calculated. Similar results were obtained also in the presence of Rb+ activated myosin ATPase and subfragment-I K+ ATPase."} {"id": "PMID:162266", "title": "Modifications of liver lysosomes in diabetic rats.", "content": "Recently investigators reported ultrastructural modifications of rat liver lysosomes which probably correlate with an increased level of blood plasma glucagon in streptozotocin-diabetes. We are investigating whether biochemical changes occur in this condition. Lysosome fragility is increased in the hepatocytes of streptozotocin-diabetic rats. Moreover the plasma activity of two glycosidases, B-N-acetylglucosaminidase and B-galactosidase, is markedly increased in streptozotocin-treated rats. Both these changes are largely prevented by insulin treatment. These findings support the idea that the morphologic and biochemical modifications of the hepatocytes, which are observed in experimental diabetes, involve the lysosomes showing an increased autophagic activity which is probably connected with enhanced liver protein catabolism.", "contents": "Modifications of liver lysosomes in diabetic rats. Recently investigators reported ultrastructural modifications of rat liver lysosomes which probably correlate with an increased level of blood plasma glucagon in streptozotocin-diabetes. We are investigating whether biochemical changes occur in this condition. Lysosome fragility is increased in the hepatocytes of streptozotocin-diabetic rats. Moreover the plasma activity of two glycosidases, B-N-acetylglucosaminidase and B-galactosidase, is markedly increased in streptozotocin-treated rats. Both these changes are largely prevented by insulin treatment. These findings support the idea that the morphologic and biochemical modifications of the hepatocytes, which are observed in experimental diabetes, involve the lysosomes showing an increased autophagic activity which is probably connected with enhanced liver protein catabolism."} {"id": "PMID:162267", "title": "[Mixed aorta-popliteal by-pass: a new proposal for the treatment of extensive ilio-femoral obstruction].", "content": "The nosological polymorphism of peripheral arterial obstruction (A.O.P.) continuously requires new surgical techniques of vascular repair. This led the AA. to develop a new composed aorto-popliteal by-pass. It consists of a proximal (aorto-femoral) synthetic segment (Dacron D.V.) which is distally anastomozed to a biological (Meadox-Dardik Biograft) femoral-popliteal segment. Indications for aorto-popliteal by-pass, technical problems, patient selection and results are here discussed.", "contents": "[Mixed aorta-popliteal by-pass: a new proposal for the treatment of extensive ilio-femoral obstruction]. The nosological polymorphism of peripheral arterial obstruction (A.O.P.) continuously requires new surgical techniques of vascular repair. This led the AA. to develop a new composed aorto-popliteal by-pass. It consists of a proximal (aorto-femoral) synthetic segment (Dacron D.V.) which is distally anastomozed to a biological (Meadox-Dardik Biograft) femoral-popliteal segment. Indications for aorto-popliteal by-pass, technical problems, patient selection and results are here discussed."} {"id": "PMID:162271", "title": "[Enzymatic study of muscle fibers of the antero-lateral wall of the abdomen in man: functional interpretation].", "content": "After a recall of muscular histo-enzymology, the authors expose the results of an analysis of the antero-lateral muscles of the abdomen. They establish a predominance of the muscular fibers, type I, that are tonic as compared with the muscular fibers, type II, that are phasic. Thus the role of support and of maintenance of the intra-peritoneal pressure by these muscles is confirmed. The tonic characteristic is also important for the functional reeducation and the electrotherapy of the abdominal wall.", "contents": "[Enzymatic study of muscle fibers of the antero-lateral wall of the abdomen in man: functional interpretation]. After a recall of muscular histo-enzymology, the authors expose the results of an analysis of the antero-lateral muscles of the abdomen. They establish a predominance of the muscular fibers, type I, that are tonic as compared with the muscular fibers, type II, that are phasic. Thus the role of support and of maintenance of the intra-peritoneal pressure by these muscles is confirmed. The tonic characteristic is also important for the functional reeducation and the electrotherapy of the abdominal wall."} {"id": "PMID:162272", "title": "[Our experience in laparoscopic diagnosis in general and emergency surgery (author's transl)].", "content": "After a brief review of the history of laparoscopy starting from the first endoscope, the authors remark on the great usefulness, ease, and essential harmlessness of the procedure. They list all the possible uses of laparoscopy in general and emergency surgery, exemplifying their claims with the illustration of personal cases and recommending widespread use of the method in surgery.", "contents": "[Our experience in laparoscopic diagnosis in general and emergency surgery (author's transl)]. After a brief review of the history of laparoscopy starting from the first endoscope, the authors remark on the great usefulness, ease, and essential harmlessness of the procedure. They list all the possible uses of laparoscopy in general and emergency surgery, exemplifying their claims with the illustration of personal cases and recommending widespread use of the method in surgery."} {"id": "PMID:162273", "title": "[The indications for laparoscopy in the diagnosis of hemoperitoneum (author's transl)].", "content": "In consideration of the well-known difficulties associated with the precise diagnosis of hemoperitoneum, the authors offer their personal experience in support of laparoscopy as a diagnostic aid in such dramatic events. They review 23 cases of emergency laparoscopy performed in the First Institute of Clinical Surgery of the University of Catania between January 1978 and January 1979. Recalling that the procedure was applied to patients as young as 3 and as old as 80, they confirm the opinion expressed from other quarters, namely that laparoscopy is an essentially harmless and rapid procedure conducive to very accurate diagnosis in view of appropriate planning of therapeutic treatment.", "contents": "[The indications for laparoscopy in the diagnosis of hemoperitoneum (author's transl)]. In consideration of the well-known difficulties associated with the precise diagnosis of hemoperitoneum, the authors offer their personal experience in support of laparoscopy as a diagnostic aid in such dramatic events. They review 23 cases of emergency laparoscopy performed in the First Institute of Clinical Surgery of the University of Catania between January 1978 and January 1979. Recalling that the procedure was applied to patients as young as 3 and as old as 80, they confirm the opinion expressed from other quarters, namely that laparoscopy is an essentially harmless and rapid procedure conducive to very accurate diagnosis in view of appropriate planning of therapeutic treatment."} {"id": "PMID:162274", "title": "[Aimed liver biopsy in the course of laparoscopy (author's transl)].", "content": "Following a discussion of the various methods that have been devised for liver biopsy, and an explanation of the advantages accruing from aimed liver biopsy in the course of laparoscopy, the authors express their preference for this method on account of its unquestionable diagnostic value, ease of execution, and freedom from complications. Accordingly, and in good agreements with other experts such as Kalk, Beck, and Dagnini, they advocate more widespread use of the procedure in liver pathology.", "contents": "[Aimed liver biopsy in the course of laparoscopy (author's transl)]. Following a discussion of the various methods that have been devised for liver biopsy, and an explanation of the advantages accruing from aimed liver biopsy in the course of laparoscopy, the authors express their preference for this method on account of its unquestionable diagnostic value, ease of execution, and freedom from complications. Accordingly, and in good agreements with other experts such as Kalk, Beck, and Dagnini, they advocate more widespread use of the procedure in liver pathology."} {"id": "PMID:162275", "title": "[Lumbago and arthrosis of posterior vertebral articulations (author's transl)].", "content": "Such Authors value the importance of the arthrosis of the posterior vertebral articulations in the genesis of back pain with or without sciatica. A particular attention must be put on the correct differential diagnosis of the various back pains. They furthermore present their casuistry. The made results through endoarticular injection of steroid and local anesthetic are good. 78% of the subjects has gone back to work; even though this treatment must be considered only one mean to permit a better physical and natural activity.", "contents": "[Lumbago and arthrosis of posterior vertebral articulations (author's transl)]. Such Authors value the importance of the arthrosis of the posterior vertebral articulations in the genesis of back pain with or without sciatica. A particular attention must be put on the correct differential diagnosis of the various back pains. They furthermore present their casuistry. The made results through endoarticular injection of steroid and local anesthetic are good. 78% of the subjects has gone back to work; even though this treatment must be considered only one mean to permit a better physical and natural activity."} {"id": "PMID:162276", "title": "[Treatment of chronic lumbosacral pain by transcutaneous electrical stimulation in laminectomized patients: preliminary results (author's transl)].", "content": "The authors have tried transcutaneous electrical stimulation for the treatment of chronic lumbosacral pain in 27 patients already treated by laminectomy without benefit. Six patients experienced a 55% mean reduction of pain; another six had a 35% reduction; and the remaining 15 a 16% reduction of pain severity. From these results and a review of published data the authors conclude that the method is of limited value in alleviating chronic lumbosacral pain in laminectomized patients.", "contents": "[Treatment of chronic lumbosacral pain by transcutaneous electrical stimulation in laminectomized patients: preliminary results (author's transl)]. The authors have tried transcutaneous electrical stimulation for the treatment of chronic lumbosacral pain in 27 patients already treated by laminectomy without benefit. Six patients experienced a 55% mean reduction of pain; another six had a 35% reduction; and the remaining 15 a 16% reduction of pain severity. From these results and a review of published data the authors conclude that the method is of limited value in alleviating chronic lumbosacral pain in laminectomized patients."} {"id": "PMID:162278", "title": "[Volumetric valuation of dural sac by standard measurement on radiographs and saccoradiculographs (author's transl)].", "content": "The Authors have planned to connect unexplained osphyalgias with dural pouch disease, through roentgenographic research. The Authors suggest a standard measurement primer to single out narrow pouches, in order to settle surgical operation.", "contents": "[Volumetric valuation of dural sac by standard measurement on radiographs and saccoradiculographs (author's transl)]. The Authors have planned to connect unexplained osphyalgias with dural pouch disease, through roentgenographic research. The Authors suggest a standard measurement primer to single out narrow pouches, in order to settle surgical operation."} {"id": "PMID:162283", "title": "TEM-induced gene mutations at enzyme loci in the mouse.", "content": "Strain DBA/2J male mice were treated with triethylenemelamine (TEM) and subsequently mated to strain C57BL/6J females. Tissues from F1 progeny produced in these crosses were then examined using starch gel electrophoresis for the presence of presumed induced mutations at a series of 11 specific enzyme loci. In the course of this study, four heritable mutations were identified at the following loci: Es-1, Ldh-1, Pgm-1, and Gpi-1. Of these four, the first two were apparently segregating in parental males and were not TEM-induced. Both of these are viable and fertile in the heterozygous and homozygous condition, and neither confers any readily apparent deleterious effect to the animal. The latter mutations (Pgm-1 and Gpi-1) are presumably induced. Although viable and fertile in the heterozygous state, we have not recovered any offsping homozygous for either of these two mutations.", "contents": "TEM-induced gene mutations at enzyme loci in the mouse. Strain DBA/2J male mice were treated with triethylenemelamine (TEM) and subsequently mated to strain C57BL/6J females. Tissues from F1 progeny produced in these crosses were then examined using starch gel electrophoresis for the presence of presumed induced mutations at a series of 11 specific enzyme loci. In the course of this study, four heritable mutations were identified at the following loci: Es-1, Ldh-1, Pgm-1, and Gpi-1. Of these four, the first two were apparently segregating in parental males and were not TEM-induced. Both of these are viable and fertile in the heterozygous and homozygous condition, and neither confers any readily apparent deleterious effect to the animal. The latter mutations (Pgm-1 and Gpi-1) are presumably induced. Although viable and fertile in the heterozygous state, we have not recovered any offsping homozygous for either of these two mutations."} {"id": "PMID:162284", "title": "Genetic effects of PR toxin in eukaryotic microorganisms.", "content": "The genetic activity of PR toxin, a mycotoxin from Penicillium roqueforti, was studied in Saccharomyces cerevisiae and Neurospora crassa. The results show that PR toxin, without enzymic activation, causes gene conversion in S. cerevisiae strains D4 and D7, reverse mutation in S. cerevisiae strain D7 and N. crassa strain N24, and mitotic crossing-over in S. cerevisiae strain D7, In the log phase cells of S. cerevisiae the effects are more pronounced at alkaline than at acid pH. The active site responsible for the genetic activity and toxicity is known. The carbonyl groups appear to play an important role in the biologic activity of this molecule.", "contents": "Genetic effects of PR toxin in eukaryotic microorganisms. The genetic activity of PR toxin, a mycotoxin from Penicillium roqueforti, was studied in Saccharomyces cerevisiae and Neurospora crassa. The results show that PR toxin, without enzymic activation, causes gene conversion in S. cerevisiae strains D4 and D7, reverse mutation in S. cerevisiae strain D7 and N. crassa strain N24, and mitotic crossing-over in S. cerevisiae strain D7, In the log phase cells of S. cerevisiae the effects are more pronounced at alkaline than at acid pH. The active site responsible for the genetic activity and toxicity is known. The carbonyl groups appear to play an important role in the biologic activity of this molecule."} {"id": "PMID:162285", "title": "A colorimetric assay of lysogenic induction designed for screening potential carcinogenic and carcinostatic agents.", "content": "Simple, rapid colorimetric tests for lysogenic induction (the derepression of a latent bacterial virus) are described. A quantitative test and a more rapid semiquantitative test are based on the assay of the beta-galactosidase synthesized from lacZ gene fused to an operon under lambda repressor control. These biochemical \"inductests\" are suitable for screening programs designed to detect agents that damage DNA and that are of potential interest in carcinogenesis and cancer chemotherapy.", "contents": "A colorimetric assay of lysogenic induction designed for screening potential carcinogenic and carcinostatic agents. Simple, rapid colorimetric tests for lysogenic induction (the derepression of a latent bacterial virus) are described. A quantitative test and a more rapid semiquantitative test are based on the assay of the beta-galactosidase synthesized from lacZ gene fused to an operon under lambda repressor control. These biochemical \"inductests\" are suitable for screening programs designed to detect agents that damage DNA and that are of potential interest in carcinogenesis and cancer chemotherapy."} {"id": "PMID:162286", "title": "7-Substituted theophyllines. Part I. Nicotinamide derivatives.", "content": "Some nicotinamides derived from 7-substituted theophyllines were prepared and pharmacologically screened. They showed a very low coronarodilatory activity, a remarkable antispastic activity and a low toxicity.", "contents": "7-Substituted theophyllines. Part I. Nicotinamide derivatives. Some nicotinamides derived from 7-substituted theophyllines were prepared and pharmacologically screened. They showed a very low coronarodilatory activity, a remarkable antispastic activity and a low toxicity."} {"id": "PMID:162288", "title": "Larsen's syndrome. Case report and discussion.", "content": "The writers present the case of a small girl affected by Larsen's syndrome. Her brother had the same syndrome. Surgical reduction of the dislocated knees was performed at the age of two months, followed by immobilisation in a spica plaster. At operation it was found that both patellae, which are cartilaginous at that age, were absent. On the basis of recent literature and the heterogeneous manifestations of the syndrome, the authors discuss the pathogenetic theories, the differential diagnosis, and the current therapeutic possibilities.", "contents": "Larsen's syndrome. Case report and discussion. The writers present the case of a small girl affected by Larsen's syndrome. Her brother had the same syndrome. Surgical reduction of the dislocated knees was performed at the age of two months, followed by immobilisation in a spica plaster. At operation it was found that both patellae, which are cartilaginous at that age, were absent. On the basis of recent literature and the heterogeneous manifestations of the syndrome, the authors discuss the pathogenetic theories, the differential diagnosis, and the current therapeutic possibilities."} {"id": "PMID:162291", "title": "[The advantages and disadvantages of ultrasound scanning in the diagnosis of ectopic pregnancies (author's transl)].", "content": "There is no need any more to demonstrate the value of echotomography in the diagnosis of extra-uterine pregnancies. All the same, the authors want to point out in the light of two cases they have had the rare, but real risk of errors made because of deficiencies in echography, which because they have excluded extra-uterine pregnancy lead to a delay which can be considerable in diagnosis. The first section deals with the features of diagnosis to be considered in extra-uterine pregnancy (an empty uterine cavity or, on the other hand, the presence of a pregnancy sac in the uterus; rarely the picture of an ovum in an ectopic position, but more often the picture of a haematosalpinx or a haematocoele). The risks of making mistakes because of insufficient information are described. These mistakes can be of serious consequence because they delay using the laparoscope (particularly likely to occur if there is the presence of a pseudo-sac of pregnancy due to separation of the decidua). Finally, the risks of making mistakes by having too much information are spelt out. These are less serious because they do lead to the use of the laparoscope. (They are wrongly diagnosed ovarian cyst, hydrosalpinx and double uterus.) In the last section the statistics given by various authors are reviewed.", "contents": "[The advantages and disadvantages of ultrasound scanning in the diagnosis of ectopic pregnancies (author's transl)]. There is no need any more to demonstrate the value of echotomography in the diagnosis of extra-uterine pregnancies. All the same, the authors want to point out in the light of two cases they have had the rare, but real risk of errors made because of deficiencies in echography, which because they have excluded extra-uterine pregnancy lead to a delay which can be considerable in diagnosis. The first section deals with the features of diagnosis to be considered in extra-uterine pregnancy (an empty uterine cavity or, on the other hand, the presence of a pregnancy sac in the uterus; rarely the picture of an ovum in an ectopic position, but more often the picture of a haematosalpinx or a haematocoele). The risks of making mistakes because of insufficient information are described. These mistakes can be of serious consequence because they delay using the laparoscope (particularly likely to occur if there is the presence of a pseudo-sac of pregnancy due to separation of the decidua). Finally, the risks of making mistakes by having too much information are spelt out. These are less serious because they do lead to the use of the laparoscope. (They are wrongly diagnosed ovarian cyst, hydrosalpinx and double uterus.) In the last section the statistics given by various authors are reviewed."} {"id": "PMID:162292", "title": "[Severe acute genital infections (Based on 100 cases). A clinical study and the contribution of laparoscopy (author's transl)].", "content": "A continuous prospective series of 100 cases of severe acute genital infections which were collected over a period of 16 months at the Gynaecological and Obstetrical Clinic of the Saint Antoine Hospital has been studies using the same protocol. Analysing the history given by these patients before the onset of the illness shows how young they were and how frequently they were nulliparous, as well as the role of intra-uterine contraceptive devices. The correlation between the clinical features and those found on laparoscopy which was carried out almost routinely shows the great advantages of this examination. The authors in their discussion have tried, by analysing groups of symptoms, to show that to make an early correct diagnosis laparoscopy has to be used in a majority of cases. It allows treatment to be instituted quickly and unhesitatingly. Furthermore, it is justified because: It is necessary to find out all lesions that are present and which are unpredictable clinically. It renders it possible to carry out therapeutic manoeuvres (such as cutting adhesions and giving antibiotics locally) and to take swabs for bacteriological examination (this will be discussed in the second part of this article).", "contents": "[Severe acute genital infections (Based on 100 cases). A clinical study and the contribution of laparoscopy (author's transl)]. A continuous prospective series of 100 cases of severe acute genital infections which were collected over a period of 16 months at the Gynaecological and Obstetrical Clinic of the Saint Antoine Hospital has been studies using the same protocol. Analysing the history given by these patients before the onset of the illness shows how young they were and how frequently they were nulliparous, as well as the role of intra-uterine contraceptive devices. The correlation between the clinical features and those found on laparoscopy which was carried out almost routinely shows the great advantages of this examination. The authors in their discussion have tried, by analysing groups of symptoms, to show that to make an early correct diagnosis laparoscopy has to be used in a majority of cases. It allows treatment to be instituted quickly and unhesitatingly. Furthermore, it is justified because: It is necessary to find out all lesions that are present and which are unpredictable clinically. It renders it possible to carry out therapeutic manoeuvres (such as cutting adhesions and giving antibiotics locally) and to take swabs for bacteriological examination (this will be discussed in the second part of this article)."} {"id": "PMID:162293", "title": "[Retardation of intra-uterine growth and its connexion with chromosome abnormalities (author's transl)].", "content": "17 chromosome abnormalities were found out of 571 small-for-dates newborn babies. 7 of these were trisomy 18, 5 trisomy 21, and 2 trisomy 13. The obstetric and paediatric implications of the fact that 3 percent of small-for-dates babies are carriers of a chromosome abnormality are discussed.", "contents": "[Retardation of intra-uterine growth and its connexion with chromosome abnormalities (author's transl)]. 17 chromosome abnormalities were found out of 571 small-for-dates newborn babies. 7 of these were trisomy 18, 5 trisomy 21, and 2 trisomy 13. The obstetric and paediatric implications of the fact that 3 percent of small-for-dates babies are carriers of a chromosome abnormality are discussed."} {"id": "PMID:162299", "title": "[Perforating injuries of the colon: primary surgery in their management (author's transl)].", "content": "Thirty four penetrating wounds of the colon in 23 patients were treated by primary surgery. Location of the injuries on the colon, associated injuries and the nature of the missile had not affected the good quality of the results. These are encouraging an attitude towards primary surgery in the management of the colon injuries. Colostomies are still indicated for patients seen lately with severe peritoneal contamination or important lesions of the posterior abdominal wall.", "contents": "[Perforating injuries of the colon: primary surgery in their management (author's transl)]. Thirty four penetrating wounds of the colon in 23 patients were treated by primary surgery. Location of the injuries on the colon, associated injuries and the nature of the missile had not affected the good quality of the results. These are encouraging an attitude towards primary surgery in the management of the colon injuries. Colostomies are still indicated for patients seen lately with severe peritoneal contamination or important lesions of the posterior abdominal wall."} {"id": "PMID:162300", "title": "[Refractory sideroblastic anaemia of primary and acquired appearance (author's transl)].", "content": "This anaemia begun at the age of 40 years. The patient died 17 years later. There was no leukaemic transformation. The authors describe the enzyme abnormalities found in the red cells (increased urosynthetase) and/for of raised serum iron levels in relatives, such that the truly acquired and apparently primary nature of this blood disease must be brought into question.", "contents": "[Refractory sideroblastic anaemia of primary and acquired appearance (author's transl)]. This anaemia begun at the age of 40 years. The patient died 17 years later. There was no leukaemic transformation. The authors describe the enzyme abnormalities found in the red cells (increased urosynthetase) and/for of raised serum iron levels in relatives, such that the truly acquired and apparently primary nature of this blood disease must be brought into question."} {"id": "PMID:162303", "title": "[Prognosis of infantile scoliosis (author's transl)].", "content": "35 cases of infantile scoliosis were studied most of whom were followed for more than 10 years. In 11 instances, the scoliosis was present in the new born. The results are compared with those obtained by other authors. The authors consider that the signs found at the first examination as described by Mehta are not reliable enough and that the subsequent evolution of the curve is important. They have observed totally regressive and partially regressive cases. They are also found that right thoraco-lumbar curves in girls were common. Criteria for a more reliable prognosis are put forward.", "contents": "[Prognosis of infantile scoliosis (author's transl)]. 35 cases of infantile scoliosis were studied most of whom were followed for more than 10 years. In 11 instances, the scoliosis was present in the new born. The results are compared with those obtained by other authors. The authors consider that the signs found at the first examination as described by Mehta are not reliable enough and that the subsequent evolution of the curve is important. They have observed totally regressive and partially regressive cases. They are also found that right thoraco-lumbar curves in girls were common. Criteria for a more reliable prognosis are put forward."} {"id": "PMID:162304", "title": "[The treatment of chronic haematogenous osteomyelitis (author's transl)].", "content": "The authors have operated on 106 cases of chronic haematogenous osteomyelitis. On 83 occasions the surgical procedure was on the bone itself and in 23 only on the soft tissues. After a one-stage bone drilling with sequestrectomy and saucerisation the results wee satisfactory in 60 p. 100 of cases. Healing was achieved in 93 p. 100 of cases after a second, third or fourth surgical procedure. An analysis of the results has led to the following conclusion; the prognosis is better in girls, in the humerus, when the onset of the disease was subacute or when it had been present for less than 1 year.", "contents": "[The treatment of chronic haematogenous osteomyelitis (author's transl)]. The authors have operated on 106 cases of chronic haematogenous osteomyelitis. On 83 occasions the surgical procedure was on the bone itself and in 23 only on the soft tissues. After a one-stage bone drilling with sequestrectomy and saucerisation the results wee satisfactory in 60 p. 100 of cases. Healing was achieved in 93 p. 100 of cases after a second, third or fourth surgical procedure. An analysis of the results has led to the following conclusion; the prognosis is better in girls, in the humerus, when the onset of the disease was subacute or when it had been present for less than 1 year."} {"id": "PMID:162305", "title": "[Lumbar venography in the diagnosis of disc herniation (author's transl)].", "content": "The authors have performed lumbar venography on 120 occasions in patients with low back pain. In 58 patients in whom the herniated disc was confirmed, the result of venography was positive and the localisation was precise in 67 cases. It is concluded that the method is safe, reliable and allows precision in diagnosis to allow better selection for surgical treatment. The examination is particularly useful in recurrent sciatica, fractures of the lumbar spine, recent or old, and in spinal stenosis. It may be associated with discography when the result is not clear cut.", "contents": "[Lumbar venography in the diagnosis of disc herniation (author's transl)]. The authors have performed lumbar venography on 120 occasions in patients with low back pain. In 58 patients in whom the herniated disc was confirmed, the result of venography was positive and the localisation was precise in 67 cases. It is concluded that the method is safe, reliable and allows precision in diagnosis to allow better selection for surgical treatment. The examination is particularly useful in recurrent sciatica, fractures of the lumbar spine, recent or old, and in spinal stenosis. It may be associated with discography when the result is not clear cut."} {"id": "PMID:162306", "title": "[Recurrent posterior dislocation of the elbow following malunion of supracondylar fracture of the humerus. Report of a case (author's transl)].", "content": "One case of recurrent posterior dislocation of the elbow after malunion of a supracondylar fracture is reported. The malunion was a posterior angulation of the epiphysis of about 30 degrees. A good result was obtained after osteotomy to correct the malunion.", "contents": "[Recurrent posterior dislocation of the elbow following malunion of supracondylar fracture of the humerus. Report of a case (author's transl)]. One case of recurrent posterior dislocation of the elbow after malunion of a supracondylar fracture is reported. The malunion was a posterior angulation of the epiphysis of about 30 degrees. A good result was obtained after osteotomy to correct the malunion."} {"id": "PMID:162307", "title": "[Infected total knee prostheses treated by Papineau's technique and arthrodesis (author's transl)].", "content": "The technique of arthrodesis of the knee after removal of an infected total prostheses is described. It was used in four cases. In the first stage, the prostheses and cement were removed, the wound was left open and knee immobilized by Hoffman external fixation. Details of the fixation are given. The second stage of filling of the wound by cancellous chips was performed two weeks later. On average, the fixation was removed after seven months. Some mechanical experiments were made to establish the best type of fixation device.", "contents": "[Infected total knee prostheses treated by Papineau's technique and arthrodesis (author's transl)]. The technique of arthrodesis of the knee after removal of an infected total prostheses is described. It was used in four cases. In the first stage, the prostheses and cement were removed, the wound was left open and knee immobilized by Hoffman external fixation. Details of the fixation are given. The second stage of filling of the wound by cancellous chips was performed two weeks later. On average, the fixation was removed after seven months. Some mechanical experiments were made to establish the best type of fixation device."} {"id": "PMID:162308", "title": "[Angulation--lengthening by cylindrical osteotomy (author's transl)].", "content": "The theory and technique of cylindrical osteotomy are described. It allows correction of angulation with some lengthening of the bone. It does not allow the correction of rotational deformities. 18 cases were operated on, 4 in the tibia and 14 in the femur.", "contents": "[Angulation--lengthening by cylindrical osteotomy (author's transl)]. The theory and technique of cylindrical osteotomy are described. It allows correction of angulation with some lengthening of the bone. It does not allow the correction of rotational deformities. 18 cases were operated on, 4 in the tibia and 14 in the femur."} {"id": "PMID:162309", "title": "[Simultaneous bilateral traumatic dislocation of the hip. Report of a case (author's transl)].", "content": "A case of simultaneous bilateral traumatic dislocation of the hip is reported. A review of the literature shows that this lesion is rare and impressive but that its treatment is not particularly difficult.", "contents": "[Simultaneous bilateral traumatic dislocation of the hip. Report of a case (author's transl)]. A case of simultaneous bilateral traumatic dislocation of the hip is reported. A review of the literature shows that this lesion is rare and impressive but that its treatment is not particularly difficult."} {"id": "PMID:162315", "title": "Endotoxin fever in the newborn kitten. The role of prostaglandins and monoamines.", "content": "In 5--10 day-old kittens at thermoneutral environmental temperature cerebroventricular injections of 10 microgram serotonin or noradrenaline caused hyperthermia and hypothermia, respectively. Central injections of 20 and 200 ng prostaglandin E1 induced hyperthermia. Monophasic fever followed the cerebroventricular injections of 0.2 or 0.002 microgram E. coli endotoxin, both in thermoneutral and moderately cool environments. In kittens pretreated with para-chlorophenylalanine (PCPA) the endotoxin induced rise in body temperature was attenuated within 60 to 90 min after the endotoxin. Indomethacin pretreatment prevented the first part of the febrile response and only a slight temperature rise occurred after a long latency. Central injections of phentolamine did not modify the fever response, while centrally applied propranolol modified the fever course so that it resembled that seen in PCPA treated kittens. The central mediation of endotoxin fever in the kitten is complex, despite that the pattern of the temperature change is simple (monophasic). Arachidonic acid metabolites and serotonin of the central nervous system may be involved in the reaction, while the activation of central noradrenergic mechanisms does not seem to be indispensable for the response. The changes in mediators are similar to those in newborn guinea pigs, although the fever course is different in the two species.", "contents": "Endotoxin fever in the newborn kitten. The role of prostaglandins and monoamines. In 5--10 day-old kittens at thermoneutral environmental temperature cerebroventricular injections of 10 microgram serotonin or noradrenaline caused hyperthermia and hypothermia, respectively. Central injections of 20 and 200 ng prostaglandin E1 induced hyperthermia. Monophasic fever followed the cerebroventricular injections of 0.2 or 0.002 microgram E. coli endotoxin, both in thermoneutral and moderately cool environments. In kittens pretreated with para-chlorophenylalanine (PCPA) the endotoxin induced rise in body temperature was attenuated within 60 to 90 min after the endotoxin. Indomethacin pretreatment prevented the first part of the febrile response and only a slight temperature rise occurred after a long latency. Central injections of phentolamine did not modify the fever response, while centrally applied propranolol modified the fever course so that it resembled that seen in PCPA treated kittens. The central mediation of endotoxin fever in the kitten is complex, despite that the pattern of the temperature change is simple (monophasic). Arachidonic acid metabolites and serotonin of the central nervous system may be involved in the reaction, while the activation of central noradrenergic mechanisms does not seem to be indispensable for the response. The changes in mediators are similar to those in newborn guinea pigs, although the fever course is different in the two species."} {"id": "PMID:162312", "title": "Visualization of collateral venous circulation during intravenous urography secondary to superior vena cava syndrome.", "content": "Transient visualization of superficial collateral abdominal veins can occur in intravenous urography in some patients with the superior vena cava syndrome. The findings are characteristic enough to lead the radiologist to the correct diagnosis. A presentation and explanation of this finding is made.", "contents": "Visualization of collateral venous circulation during intravenous urography secondary to superior vena cava syndrome. Transient visualization of superficial collateral abdominal veins can occur in intravenous urography in some patients with the superior vena cava syndrome. The findings are characteristic enough to lead the radiologist to the correct diagnosis. A presentation and explanation of this finding is made."} {"id": "PMID:162311", "title": "Prune belly syndrome in young females.", "content": "The cases of three females with deficiency of the abdominal muscles are reported. In one, severe urinary tract changes, typical of the prune belly syndrome in males was found. Twenty-three cases of prune belly syndrome in young females are reviewed. In over half, urinary tract changes were present. Intravenous urography and micturating cystourethrography are indicated in all young females with reduced abdominal musculature.", "contents": "Prune belly syndrome in young females. The cases of three females with deficiency of the abdominal muscles are reported. In one, severe urinary tract changes, typical of the prune belly syndrome in males was found. Twenty-three cases of prune belly syndrome in young females are reviewed. In over half, urinary tract changes were present. Intravenous urography and micturating cystourethrography are indicated in all young females with reduced abdominal musculature."} {"id": "PMID:162318", "title": "[Down syndrome: cardiotocographic alterations (author's transl)].", "content": "The Authors describe the results of a study on the cardiotocographic tracings during labour of pregnant women, whose fetuses were affected by Down syndrome. The high incidence of cardiotocographic alterations in these fetuses does not seem to be in relation with congenital cardiac disease.", "contents": "[Down syndrome: cardiotocographic alterations (author's transl)]. The Authors describe the results of a study on the cardiotocographic tracings during labour of pregnant women, whose fetuses were affected by Down syndrome. The high incidence of cardiotocographic alterations in these fetuses does not seem to be in relation with congenital cardiac disease."} {"id": "PMID:162319", "title": "Effect of ubiquinone-homologs on the sensitivity of mitochondrial ATPase to energy transfer inhibitors.", "content": "Short-chain ubiquinone (UQ-3) abolishes oligomycin sensitivity of ATPase in submitochondrial particles and the effect is reversed by long-chain ubiquinone (UQ-7). Ubiquinone-3 also abolishes DCCD sensitivity of ATPase in submitochondrial particles but the effect is not reversed by long-chain ubiquinones. These data suggest that ubiquinone interferes with energy transfer process by interaction with mitochondrial ATPase.", "contents": "Effect of ubiquinone-homologs on the sensitivity of mitochondrial ATPase to energy transfer inhibitors. Short-chain ubiquinone (UQ-3) abolishes oligomycin sensitivity of ATPase in submitochondrial particles and the effect is reversed by long-chain ubiquinone (UQ-7). Ubiquinone-3 also abolishes DCCD sensitivity of ATPase in submitochondrial particles but the effect is not reversed by long-chain ubiquinones. These data suggest that ubiquinone interferes with energy transfer process by interaction with mitochondrial ATPase."} {"id": "PMID:162316", "title": "The clinical significance of an elevated excretion of xanthurenic acid in psychiatric patients.", "content": "This study investigations whether the synthesis of nicotinamide out of L-tryptophan is disordered in depression or in anxiety. To this end the excretion of xanthurenic acid (XA) in 24 hours urine was measured after administration of an oral loading dose of 5 grams L-tryptophan. The subjects were depressive, anxious, and alcoholic patients, while other psychiatric patients, served as control group. Anxiety and not depression is the clinical correlate of an elevated excretion of XA. Liver disorder and vitamin B-6 deficiency have to be excluded. A psychiatric control group is necessary.", "contents": "The clinical significance of an elevated excretion of xanthurenic acid in psychiatric patients. This study investigations whether the synthesis of nicotinamide out of L-tryptophan is disordered in depression or in anxiety. To this end the excretion of xanthurenic acid (XA) in 24 hours urine was measured after administration of an oral loading dose of 5 grams L-tryptophan. The subjects were depressive, anxious, and alcoholic patients, while other psychiatric patients, served as control group. Anxiety and not depression is the clinical correlate of an elevated excretion of XA. Liver disorder and vitamin B-6 deficiency have to be excluded. A psychiatric control group is necessary."} {"id": "PMID:162328", "title": "The effect of glycosaminoglycans (GAG) on the intramolecular bindings of collagen.", "content": "The subfractions of collagen (alpha, beta and gamma components) precipitated from neutral collagen solution by gelation corresponded to those of collagen precipitated in the same conditions (ion environments) and in the presence of chondroitin-4-sulphate. Collagen fibrils precipitated delayed in the presence of heparin poor in beta chains and rich in alpha chains. The delaying effect of oversulphated GAG on the in vitro fibril formation can be explained by the release or prevention of ion-type intramolecular bonds of collagen. The possible in vivo significance of the above bonds is discussed.", "contents": "The effect of glycosaminoglycans (GAG) on the intramolecular bindings of collagen. The subfractions of collagen (alpha, beta and gamma components) precipitated from neutral collagen solution by gelation corresponded to those of collagen precipitated in the same conditions (ion environments) and in the presence of chondroitin-4-sulphate. Collagen fibrils precipitated delayed in the presence of heparin poor in beta chains and rich in alpha chains. The delaying effect of oversulphated GAG on the in vitro fibril formation can be explained by the release or prevention of ion-type intramolecular bonds of collagen. The possible in vivo significance of the above bonds is discussed."} {"id": "PMID:162329", "title": "Effect of the fungal toxin (zearalenone) on the reproductive system and fertility of male and female rats.", "content": "The fertility-inhibiting effects of long-term (8 weeks) consumption of maize infected with a fungus producing F2 toxin (zearalenone) was studied in adult male and female albino rats. The fertility rate was further decreased by 25-30% if the animals were kept on contaminated diet up to 14 weeks. The gonadal weight was decreased, follicular maturation and spermatogenesis were disturbed. The toxic diet consumed by mothers during pregnancy and lactation induced permanent changes in reproductive organs, disorders in vaginal cyclicity and disturbed fertility in the offspring. Neonatal administration of purified F2 toxin provoked similar changes. It is suggested that this fungal toxin may cause sterility syndrome in the offspring, similar to that produced by androgen or estrogen administration.", "contents": "Effect of the fungal toxin (zearalenone) on the reproductive system and fertility of male and female rats. The fertility-inhibiting effects of long-term (8 weeks) consumption of maize infected with a fungus producing F2 toxin (zearalenone) was studied in adult male and female albino rats. The fertility rate was further decreased by 25-30% if the animals were kept on contaminated diet up to 14 weeks. The gonadal weight was decreased, follicular maturation and spermatogenesis were disturbed. The toxic diet consumed by mothers during pregnancy and lactation induced permanent changes in reproductive organs, disorders in vaginal cyclicity and disturbed fertility in the offspring. Neonatal administration of purified F2 toxin provoked similar changes. It is suggested that this fungal toxin may cause sterility syndrome in the offspring, similar to that produced by androgen or estrogen administration."} {"id": "PMID:162330", "title": "ATPase activity of sulfhydryl-modified cardiac myosin from normal and isoproterenol-treated rats.", "content": "The possible role of sulfhydryl groups in the adaptation of cardiac myosin to work overload has been examined. The functional integrity of sulfhydryl groups was evaluated by measurement of Ca2+- and K+-(EDTA)-ATPase activities of myosins following sulfhydryl modification. No activation of Ca2+-ATPase of normal rat cardiac myosin was observed after pMB or NEM pretreatment. The decrease in Ca2+-ATPase of myosin from hypertrophied hearts was eliminated following sulfhydryl modification: moreover, slight stimulation of Ca2+-ATPase was observed. An increase in KCl concentration did not stimulate the Ca2+-ATPase of NEM-modified myosins obtained from either control or hypertrophied hearts. The sulfhydryl content of rat cardiac myosin expressed as moles of SH per 10(5) g of myosin was 6.99 +/- 0.30 and in IPR-induced hypertrophy did not change it significantly. In the authors' opinion an alteration in the integrity of the sulfhydryl groups may be responsible for the functional partition (decreased Ca2+-ATpase with unchanged K+-[EDTA]-ATPase activity) of myosin from hypertrophied hearts.", "contents": "ATPase activity of sulfhydryl-modified cardiac myosin from normal and isoproterenol-treated rats. The possible role of sulfhydryl groups in the adaptation of cardiac myosin to work overload has been examined. The functional integrity of sulfhydryl groups was evaluated by measurement of Ca2+- and K+-(EDTA)-ATPase activities of myosins following sulfhydryl modification. No activation of Ca2+-ATPase of normal rat cardiac myosin was observed after pMB or NEM pretreatment. The decrease in Ca2+-ATPase of myosin from hypertrophied hearts was eliminated following sulfhydryl modification: moreover, slight stimulation of Ca2+-ATPase was observed. An increase in KCl concentration did not stimulate the Ca2+-ATPase of NEM-modified myosins obtained from either control or hypertrophied hearts. The sulfhydryl content of rat cardiac myosin expressed as moles of SH per 10(5) g of myosin was 6.99 +/- 0.30 and in IPR-induced hypertrophy did not change it significantly. In the authors' opinion an alteration in the integrity of the sulfhydryl groups may be responsible for the functional partition (decreased Ca2+-ATpase with unchanged K+-[EDTA]-ATPase activity) of myosin from hypertrophied hearts."} {"id": "PMID:162331", "title": "Hybridization of DNA's from Neurospora crassa strains may indicate base sequence alterations as a consequence of genetic transformation.", "content": "Deoxyribonucleic acids of Neurospora crassa strains involved in genetic transformation experiments were studied by means of DNA-DNA hybridization. No significant difference was detected in the extent of hybridization reassociating 32P-DNA of an inositol-requiring recipient strain with an excess amount of unlabelled homologous DNA and that of the transformed, spontaneous revertant and wild-type strains. Studies on the thermal stability of hybrids revealed 1.2-1.7% heterology between the recipient and transformant DNA's. The spontaneous revertant and wild-type strains proved to be homologous with the recipient strain. We suppose that the heterology we measured is the result of the alteration of the nucleotide sequences caused by the multilocal integration of transforming DNA into the recipient genome.", "contents": "Hybridization of DNA's from Neurospora crassa strains may indicate base sequence alterations as a consequence of genetic transformation. Deoxyribonucleic acids of Neurospora crassa strains involved in genetic transformation experiments were studied by means of DNA-DNA hybridization. No significant difference was detected in the extent of hybridization reassociating 32P-DNA of an inositol-requiring recipient strain with an excess amount of unlabelled homologous DNA and that of the transformed, spontaneous revertant and wild-type strains. Studies on the thermal stability of hybrids revealed 1.2-1.7% heterology between the recipient and transformant DNA's. The spontaneous revertant and wild-type strains proved to be homologous with the recipient strain. We suppose that the heterology we measured is the result of the alteration of the nucleotide sequences caused by the multilocal integration of transforming DNA into the recipient genome."} {"id": "PMID:162332", "title": "[Immunomechanisms in drug-induced hemolytic anemias].", "content": "Among the acquired hemolytic anemias, drug-induced immune hemolytic anemias (IHA) play a significant role. Many different drugs are capable of causing IHA, alphamethyldopa and penicillins have been responsible for the greatest number of cases. For the majority of the other drugs single cases of IHA are reported. Drug-induced immune hemolysis may be mediated by different immune mechanisms including the immune cytotoxicity type (penicillins and cephalosporins) with predominantly extravascular hemolysis. Immune hemolysis of most other drugs is due to immune complexes formed by the drug and specific antibodies leading to intravascular hemolysis in the presence of complement activation. So far, the autoimmune type of IHA caused by alphamethyldopa is unexplained, serologically this form cannot be distinguished from warm antibody auto-IHA. The clinical importance of drug-induced IHA depends on the severity of anemia and the problem of diagnosis leading to adequate therapeutic measures. Only a small number of cases showing a positive direct antiglobulin (Coombs') test caused by drugs will develop IHA. Therefore this finding does not require absolutely withdrawal of the drug, but careful observation of the patient. The diagnosis of drug-induced IHA is necessary for its distinction from auto-IHA and other secondary IHA. The study of such IHA has great importance for the understanding of other drug-induced cytopenias and may give explanations of the pathogenetic mechanisms of yet unexplained autoimmune phenomena.", "contents": "[Immunomechanisms in drug-induced hemolytic anemias]. Among the acquired hemolytic anemias, drug-induced immune hemolytic anemias (IHA) play a significant role. Many different drugs are capable of causing IHA, alphamethyldopa and penicillins have been responsible for the greatest number of cases. For the majority of the other drugs single cases of IHA are reported. Drug-induced immune hemolysis may be mediated by different immune mechanisms including the immune cytotoxicity type (penicillins and cephalosporins) with predominantly extravascular hemolysis. Immune hemolysis of most other drugs is due to immune complexes formed by the drug and specific antibodies leading to intravascular hemolysis in the presence of complement activation. So far, the autoimmune type of IHA caused by alphamethyldopa is unexplained, serologically this form cannot be distinguished from warm antibody auto-IHA. The clinical importance of drug-induced IHA depends on the severity of anemia and the problem of diagnosis leading to adequate therapeutic measures. Only a small number of cases showing a positive direct antiglobulin (Coombs') test caused by drugs will develop IHA. Therefore this finding does not require absolutely withdrawal of the drug, but careful observation of the patient. The diagnosis of drug-induced IHA is necessary for its distinction from auto-IHA and other secondary IHA. The study of such IHA has great importance for the understanding of other drug-induced cytopenias and may give explanations of the pathogenetic mechanisms of yet unexplained autoimmune phenomena."} {"id": "PMID:162333", "title": "[The hemolytic syndrome in subacute bacterial endocarditis].", "content": "Long lasting subacute bacterial endocarditis often presents with marked anemia. Infective mechanisms and hemolysis are considered as most important pathophysiological mechanisms. Pronounced hemolytic anemia, thrombocytopenia and edema observed in two cases are possible misleading symptoms in the diagnosis of subacute bacterial endocarditis.", "contents": "[The hemolytic syndrome in subacute bacterial endocarditis]. Long lasting subacute bacterial endocarditis often presents with marked anemia. Infective mechanisms and hemolysis are considered as most important pathophysiological mechanisms. Pronounced hemolytic anemia, thrombocytopenia and edema observed in two cases are possible misleading symptoms in the diagnosis of subacute bacterial endocarditis."} {"id": "PMID:162334", "title": "[Clinical relevance of circulating immune complexes in patients with systemic lupus erythematosus and chronic polyarthritis].", "content": "Using a solid phase C1q assay, circulating immune complexes (IC) were detected in 15 of 55 patients with rheumatoid arthritis (RA) and 6 of 14 patients with systemic lupus erythematosus (SLE). In contrast to RA, presence of IC correlated to clinical disease activity in SLE patients. Preliminary short term follow up studies revealed additional differences between RA and SLE: whereas persistence of IC was noted in the patients with SLE, rapid changes of IC levels were observed in RA.", "contents": "[Clinical relevance of circulating immune complexes in patients with systemic lupus erythematosus and chronic polyarthritis]. Using a solid phase C1q assay, circulating immune complexes (IC) were detected in 15 of 55 patients with rheumatoid arthritis (RA) and 6 of 14 patients with systemic lupus erythematosus (SLE). In contrast to RA, presence of IC correlated to clinical disease activity in SLE patients. Preliminary short term follow up studies revealed additional differences between RA and SLE: whereas persistence of IC was noted in the patients with SLE, rapid changes of IC levels were observed in RA."} {"id": "PMID:162335", "title": "[Essential cryoglobulinemia with accompanying angioneurotic edema].", "content": "A case report of a patient with essential cryoglobulinemia and episodes of angioedema caused by an acquired C1 inhibitor deficiency is presented. The patient had high levels of circulating immune complexes. In the course of complement activation C1 inhibitor may be consumed and the resulting C1 inhibitor deficiency led to the occurrence of angioedema.", "contents": "[Essential cryoglobulinemia with accompanying angioneurotic edema]. A case report of a patient with essential cryoglobulinemia and episodes of angioedema caused by an acquired C1 inhibitor deficiency is presented. The patient had high levels of circulating immune complexes. In the course of complement activation C1 inhibitor may be consumed and the resulting C1 inhibitor deficiency led to the occurrence of angioedema."} {"id": "PMID:162336", "title": "[A method for the detection of suppressor lymphocytes and its clinical use].", "content": "Suppressor cells play a major role in immune regulation and supervision. Unspecific suppressor cells can be stimulated by Concanavalin A (ConA) in a concentration of 1-50 micrograms/ml. Absorbed pooled human AB serum is the optimal serum source. Monocytes are necessary to induce suppressor cells. Preincubation of lymphocytes abolishes the suppressor cell inducibility. Different ConA incubation periods show two suppressor peaks, the first on day 0-1, the second on day 4-6. It is concluded, therefore, that we deal with two populations of suppressor cells. The first of these seems to resemble the spontaneous in vivo suppressor level, needs not to be activated by ConA but is rapidly inactivated without permanent antigeneic stimulus. The second peak consists of suppressor cells which are activated by a ConA stimulation of at least 3-4 days. Another conclusion can be drawn from these data: The conventional control system for the ConA induction of suppressor cells is not the optimal one, because the spontaneous suppressor cells are not included within this system, although they perhaps give a better insight into the actual immune status.", "contents": "[A method for the detection of suppressor lymphocytes and its clinical use]. Suppressor cells play a major role in immune regulation and supervision. Unspecific suppressor cells can be stimulated by Concanavalin A (ConA) in a concentration of 1-50 micrograms/ml. Absorbed pooled human AB serum is the optimal serum source. Monocytes are necessary to induce suppressor cells. Preincubation of lymphocytes abolishes the suppressor cell inducibility. Different ConA incubation periods show two suppressor peaks, the first on day 0-1, the second on day 4-6. It is concluded, therefore, that we deal with two populations of suppressor cells. The first of these seems to resemble the spontaneous in vivo suppressor level, needs not to be activated by ConA but is rapidly inactivated without permanent antigeneic stimulus. The second peak consists of suppressor cells which are activated by a ConA stimulation of at least 3-4 days. Another conclusion can be drawn from these data: The conventional control system for the ConA induction of suppressor cells is not the optimal one, because the spontaneous suppressor cells are not included within this system, although they perhaps give a better insight into the actual immune status."} {"id": "PMID:162338", "title": "[Effect of motor stimulation and stretching on afferent activity of the neuromuscular spindle isolated from the frog].", "content": "The arrangement of muscle spindles in m. ext. long. dig. IV has been examined by microdissection. It is confirmed that spindle systems generally appear to consist of individual receptors. Stimulation effects of fast motor fibres (conduction velocities greater than 12 m/sec) on the spindles of the same muscle were studied. Receptors were isolated with their nerves and the appropriate spinal roots, the latter ones were used for stimulating efferent fibres and recording sensory discharges. Single shocks to the ventral root filaments caused afferent responses ranging from a single action potential to a train of impulses. During repetitive stimulation (train of stimuli at frequency of 10 to 150/sec) a marked increase in afferent activity was found. Afferent activity could be driven by the frequency of stimuli (\"driving\") and the stimulus/action potentials ratio varied from 1:1 to 1:3 or more. The rate of sensory discharge depended on the frequency of stimuli: the maximum effect, was attained at 30 to 50 stimuli/sec and, in the most responsive receptors, up to 80 stimuli/sec. Slight increases of the initial lengths of the receptors caused facilitation of sensory responses to motor stimulation. Moreover, impairing effects, which appear during sustained or high-frequency stimulation, possibly related to fatigue in intrafusal neuromuscular transmission, could be relieved by increasing the initial length. The repetitive stimulation of fast fusimotor fibres increased both dynamic and static responses and also raised the afferent activity after a period of stretching, when usually a depression occurs; these effects varied according to the preparation, its initial tension and the frequency of stimulation. The main feature of the examined motor fibres, when stimulated, is the constant excitatory action on muscle spindle static response. Results are discussed. It is suggested that the different characteristics of intrafusal muscle fibres, the receptor initial tension and the frequency of motor units discharges, may together affect muscle spindles static or dynamic performance.", "contents": "[Effect of motor stimulation and stretching on afferent activity of the neuromuscular spindle isolated from the frog]. The arrangement of muscle spindles in m. ext. long. dig. IV has been examined by microdissection. It is confirmed that spindle systems generally appear to consist of individual receptors. Stimulation effects of fast motor fibres (conduction velocities greater than 12 m/sec) on the spindles of the same muscle were studied. Receptors were isolated with their nerves and the appropriate spinal roots, the latter ones were used for stimulating efferent fibres and recording sensory discharges. Single shocks to the ventral root filaments caused afferent responses ranging from a single action potential to a train of impulses. During repetitive stimulation (train of stimuli at frequency of 10 to 150/sec) a marked increase in afferent activity was found. Afferent activity could be driven by the frequency of stimuli (\"driving\") and the stimulus/action potentials ratio varied from 1:1 to 1:3 or more. The rate of sensory discharge depended on the frequency of stimuli: the maximum effect, was attained at 30 to 50 stimuli/sec and, in the most responsive receptors, up to 80 stimuli/sec. Slight increases of the initial lengths of the receptors caused facilitation of sensory responses to motor stimulation. Moreover, impairing effects, which appear during sustained or high-frequency stimulation, possibly related to fatigue in intrafusal neuromuscular transmission, could be relieved by increasing the initial length. The repetitive stimulation of fast fusimotor fibres increased both dynamic and static responses and also raised the afferent activity after a period of stretching, when usually a depression occurs; these effects varied according to the preparation, its initial tension and the frequency of stimulation. The main feature of the examined motor fibres, when stimulated, is the constant excitatory action on muscle spindle static response. Results are discussed. It is suggested that the different characteristics of intrafusal muscle fibres, the receptor initial tension and the frequency of motor units discharges, may together affect muscle spindles static or dynamic performance."} {"id": "PMID:162339", "title": "[Effects of acetylcholine and succinylcholine on isolated frog neuromuscular spindle].", "content": "The mode of action of acetylcholine (ACh) and succinylcholine (SCh) on the isolated frog's muscle spindle has been studied. Receptor afferent nervous supply was maintained; the appropriate spinal roots were dissected for stimulating motor axons and recording from sensory fibres. Excitatory effects on the afferent activity, when the receptor was held still and during stretching, were found with ACh or SCh concentrations of 10(-8) to 10(-3); 10(-6) g/ml being usually effective. These effects are similar to those obtained by stimulating fusimotor nerve fibres. The contractile activity of intrafusal muscle fibres which occurred during these effects was observed. Seldom, and only for high concentrations of ACh and SCh, a decrease in afferent activity following the excitatory effects was found. Tubocurarine chloride (10(-5)-10(04) g/ml) in the bath prevented both motor fibres and drugs effects. Sometimes slight transient excitation occurred at very high concentrations of the two tested substances; however, this effect was prevented by stronger curarization. The observed blocking effects were always reversed by removing tubocurarine from the bath. No more excitatory effects by motor fibres stimulation and by ACh and SCh action could be found after destruction of intrafusal muscle fibres, by pinching them as close as possible to the ends of the spindle. It is suggested that ACh and SCh act indirectly by causing mechanical changes in intrafusal muscle fibres, and that a direct action on sensory nerve endings, if any, cannot, by itself, increase the afferent activity of the receptor.", "contents": "[Effects of acetylcholine and succinylcholine on isolated frog neuromuscular spindle]. The mode of action of acetylcholine (ACh) and succinylcholine (SCh) on the isolated frog's muscle spindle has been studied. Receptor afferent nervous supply was maintained; the appropriate spinal roots were dissected for stimulating motor axons and recording from sensory fibres. Excitatory effects on the afferent activity, when the receptor was held still and during stretching, were found with ACh or SCh concentrations of 10(-8) to 10(-3); 10(-6) g/ml being usually effective. These effects are similar to those obtained by stimulating fusimotor nerve fibres. The contractile activity of intrafusal muscle fibres which occurred during these effects was observed. Seldom, and only for high concentrations of ACh and SCh, a decrease in afferent activity following the excitatory effects was found. Tubocurarine chloride (10(-5)-10(04) g/ml) in the bath prevented both motor fibres and drugs effects. Sometimes slight transient excitation occurred at very high concentrations of the two tested substances; however, this effect was prevented by stronger curarization. The observed blocking effects were always reversed by removing tubocurarine from the bath. No more excitatory effects by motor fibres stimulation and by ACh and SCh action could be found after destruction of intrafusal muscle fibres, by pinching them as close as possible to the ends of the spindle. It is suggested that ACh and SCh act indirectly by causing mechanical changes in intrafusal muscle fibres, and that a direct action on sensory nerve endings, if any, cannot, by itself, increase the afferent activity of the receptor."} {"id": "PMID:162341", "title": "Circadian periodicity of plasma prolactin in some neurological diseases.", "content": "The circadian rhythmicity of plasma PRL has been studied in some neurological diseases in which hypothalamic involvement or abnormalities of brain neurotransmitters has been postulated. 11 patients with Steinert's myotonic dystrophy, 7 with cluster headache and 10 with Huntington's chorea have been studied. By the mean cosinor procedure, a significant circadian rhythm of plasma PRL has been observed both in Steinert's disease and in cluster headache, whereas a circadian periodicity is not detectable in Huntington's chorea, a degenerative disorder affecting the basal ganglia, the hypothalamus and many other areas of the CNS.", "contents": "Circadian periodicity of plasma prolactin in some neurological diseases. The circadian rhythmicity of plasma PRL has been studied in some neurological diseases in which hypothalamic involvement or abnormalities of brain neurotransmitters has been postulated. 11 patients with Steinert's myotonic dystrophy, 7 with cluster headache and 10 with Huntington's chorea have been studied. By the mean cosinor procedure, a significant circadian rhythm of plasma PRL has been observed both in Steinert's disease and in cluster headache, whereas a circadian periodicity is not detectable in Huntington's chorea, a degenerative disorder affecting the basal ganglia, the hypothalamus and many other areas of the CNS."} {"id": "PMID:162342", "title": "The stimulation of photophosphorylation and ATPase by artificial redox mediators in chromatophores of Rhodopseudomonas capsulata at different redox potentials.", "content": "(1) Inhibition of cyclic phosphorylation in chromatophores of Rhodopseudomonas capsulata by antimycin A can be fully reversed by artificial redox mediators, provided the ambient redox potential is maintained around 200 mV. The redox mediator need not be a hydrogen carrier in its reduced form, N-methyl-phenazonium methosulfate and N,N,N',N'-tetramethyl-p-phenylenediamine being equally effective. However, the mediator needs to be lipophilic. Endogenous cyclic phosphorylation is fastest around 130 mV. A shift to 200 mV can also be observed if high concentrations of artificial redox mediator are present in the absence of antimycin. (2) ATPase activity of Rhodopseudomonas capsulata, in the light as well as in the dark, activated or not activated by inorganic phosphate, can also be stimulated by N-methylphenazonium methosulfate. This stimulation is highest at redox potentials between 60 to 80 mV and is sensitive to antimycin A. In this case N,N,N',N-tetramethyl-p-phenylenediamine is much less effective.", "contents": "The stimulation of photophosphorylation and ATPase by artificial redox mediators in chromatophores of Rhodopseudomonas capsulata at different redox potentials. (1) Inhibition of cyclic phosphorylation in chromatophores of Rhodopseudomonas capsulata by antimycin A can be fully reversed by artificial redox mediators, provided the ambient redox potential is maintained around 200 mV. The redox mediator need not be a hydrogen carrier in its reduced form, N-methyl-phenazonium methosulfate and N,N,N',N'-tetramethyl-p-phenylenediamine being equally effective. However, the mediator needs to be lipophilic. Endogenous cyclic phosphorylation is fastest around 130 mV. A shift to 200 mV can also be observed if high concentrations of artificial redox mediator are present in the absence of antimycin. (2) ATPase activity of Rhodopseudomonas capsulata, in the light as well as in the dark, activated or not activated by inorganic phosphate, can also be stimulated by N-methylphenazonium methosulfate. This stimulation is highest at redox potentials between 60 to 80 mV and is sensitive to antimycin A. In this case N,N,N',N-tetramethyl-p-phenylenediamine is much less effective."} {"id": "PMID:162343", "title": "Low-back pain among electric power supply workers and their attitude toward its prevention and the treatment.", "content": "Low-back pain among electric power supply workers and their opinions about the ways to prevent and relieve the disorder were investigated. A questionnaire study revealed that 38.7% of 6,272 electric power supply workers were suffering from low-back pain, including severe pain resulting in frequent absenteeism or requiring occasional rest from work. Chronological analysis of the occurrence of the disorder revealed that the incidence of gradually developing pain has increased and that improper working posture and overwork have become more important as etiological factors. Rest from work was found to be the most effective way of relieving pain, while any medical treatment which did not include rest was useless. Low-back pain among these workers is believed to have resulted from rapid and intensified work as required by increasing demand and mechanization, greater mental stress and improper working posture. As preventive measures, it is necessary to improve working hours and to lighten the rate of work. In order to relieve pain, the employers should permit the workers to absent themselves from work quickly following an attack. Discrepancy between workers' opinions and both actual causation of low-back pain and actual effectiveness of medical treatment is discussed.", "contents": "Low-back pain among electric power supply workers and their attitude toward its prevention and the treatment. Low-back pain among electric power supply workers and their opinions about the ways to prevent and relieve the disorder were investigated. A questionnaire study revealed that 38.7% of 6,272 electric power supply workers were suffering from low-back pain, including severe pain resulting in frequent absenteeism or requiring occasional rest from work. Chronological analysis of the occurrence of the disorder revealed that the incidence of gradually developing pain has increased and that improper working posture and overwork have become more important as etiological factors. Rest from work was found to be the most effective way of relieving pain, while any medical treatment which did not include rest was useless. Low-back pain among these workers is believed to have resulted from rapid and intensified work as required by increasing demand and mechanization, greater mental stress and improper working posture. As preventive measures, it is necessary to improve working hours and to lighten the rate of work. In order to relieve pain, the employers should permit the workers to absent themselves from work quickly following an attack. Discrepancy between workers' opinions and both actual causation of low-back pain and actual effectiveness of medical treatment is discussed."} {"id": "PMID:162340", "title": "[Behavior of certain acid hydrolases in the central nervous systems of various mammals].", "content": "The activity of several acid hydrolases in different sections of the C.N.S. of various mammalian has been evaluated. The enzymes which have been studied are: beta-glucosidase, beta-galactosidase, beta-N-acetylglucosaminidase, beta-N-acetylgalactosaminidase, beta-glucuronidase, alpha-mannosidase. The enzymes show a higher activity in the gray matter than in the white matter. The results are interpreted on the assumption that glyco-lipoprotein turnover is higher in the gray matter than in the white matter, since myelin, which is the major component of the white matter, is a relatively stable structures.", "contents": "[Behavior of certain acid hydrolases in the central nervous systems of various mammals]. The activity of several acid hydrolases in different sections of the C.N.S. of various mammalian has been evaluated. The enzymes which have been studied are: beta-glucosidase, beta-galactosidase, beta-N-acetylglucosaminidase, beta-N-acetylgalactosaminidase, beta-glucuronidase, alpha-mannosidase. The enzymes show a higher activity in the gray matter than in the white matter. The results are interpreted on the assumption that glyco-lipoprotein turnover is higher in the gray matter than in the white matter, since myelin, which is the major component of the white matter, is a relatively stable structures."} {"id": "PMID:162358", "title": "[A case of relapsing mesenchymatous tumour of the abdominal wall with metastases (author's transl)].", "content": "It is classical to consider desmoid tumours as an entity with only a local prognosis, conditioned by the frequency of relapses. In this respect, they are different from other mesenchymatous tumours, fibrosarcomas in particular which have a poorer prognosis. The authors report the case of a 23 years old man with a tumour of the abdominal wall, which in the early stages resembled a desmoid tumour, but the development of metastases suggested a sarcoma. This observation seems to make doubtful the distinction between desmoid tumour and fibrosarcoma, and thus the prognosis of tumours with a desmoid appearance. Under these conditions, this term should only be used for descriptive purposes and has no prognostic value.", "contents": "[A case of relapsing mesenchymatous tumour of the abdominal wall with metastases (author's transl)]. It is classical to consider desmoid tumours as an entity with only a local prognosis, conditioned by the frequency of relapses. In this respect, they are different from other mesenchymatous tumours, fibrosarcomas in particular which have a poorer prognosis. The authors report the case of a 23 years old man with a tumour of the abdominal wall, which in the early stages resembled a desmoid tumour, but the development of metastases suggested a sarcoma. This observation seems to make doubtful the distinction between desmoid tumour and fibrosarcoma, and thus the prognosis of tumours with a desmoid appearance. Under these conditions, this term should only be used for descriptive purposes and has no prognostic value."} {"id": "PMID:162354", "title": "[Epidemiological aspects of Huntington chorea in the Genoa region from 1930 to 1977 (author's transl)].", "content": "As a preliminary approach to an epidemiological investigation of Huntington's disease, the authors report the incidence of admissions of these patients to both Neurological and Psychiatric Departments in Genoa and surrounding region from 1930 to 1977. The number of patients (84 cases) and their family history (225 cases of Chorea in the ancestors) suggest a prevalence of Huntington's disease remarkably higher (about 28 cases out of 100,000 inhabitants) than it is usually estimated. Further studies are however required to assess the distribution of the disease in the whole population of the region.", "contents": "[Epidemiological aspects of Huntington chorea in the Genoa region from 1930 to 1977 (author's transl)]. As a preliminary approach to an epidemiological investigation of Huntington's disease, the authors report the incidence of admissions of these patients to both Neurological and Psychiatric Departments in Genoa and surrounding region from 1930 to 1977. The number of patients (84 cases) and their family history (225 cases of Chorea in the ancestors) suggest a prevalence of Huntington's disease remarkably higher (about 28 cases out of 100,000 inhabitants) than it is usually estimated. Further studies are however required to assess the distribution of the disease in the whole population of the region."} {"id": "PMID:162359", "title": "[Early control laparoscopy after tubal microsurgery (author's transl)].", "content": "It is essential to carry out laparoscopic control to determine the result of plastic tubal surgery. This is classically done 12 to 18 months after the operation, yet it has been suggested that this control should be carried out earlier between the 4th and the 8th weeks or even on the 8th day following the operation. The authors have carried out 63 early control laparoscopies after microsurgical operations on the tube at different dates: 33 times between 4 and 8 weeks after the operation, 5 times between the 10th and the 13th day, and 25 times on the 8th day. They are in favour of early laparoscopic control with the reserve that it will require much more experience to tell whether the procedure is harmless.", "contents": "[Early control laparoscopy after tubal microsurgery (author's transl)]. It is essential to carry out laparoscopic control to determine the result of plastic tubal surgery. This is classically done 12 to 18 months after the operation, yet it has been suggested that this control should be carried out earlier between the 4th and the 8th weeks or even on the 8th day following the operation. The authors have carried out 63 early control laparoscopies after microsurgical operations on the tube at different dates: 33 times between 4 and 8 weeks after the operation, 5 times between the 10th and the 13th day, and 25 times on the 8th day. They are in favour of early laparoscopic control with the reserve that it will require much more experience to tell whether the procedure is harmless."} {"id": "PMID:162355", "title": "R.H.I.S.A. -- cysternography study in sporadic choreo-athetotic syndrome accompanied with dementia (sporadic Huntington disease).", "content": "Seven patients who suffered from choreo-athetotic movements, accompanied by slowly progressive mental and affective decline over several years, without hereditary background, were admitted for clinical and psychodiagnostic tests. Laboratory examinations and anamnestic data were negative, and therefore a presumed diagnosis of sporadic Huntington disease was made. In order to verify the diagnosis, we had done P.E.G. -- Contrast study, and R.H.I.S.A. -- Cysternography. The P.E.G. -- Contrast demonstrated an enlargement of the sub-arachnoidal space and a symmetrical enlargement of the ventricular System, that may represent cortical and sub-cortical atrophy. The R.H.I.S.A. -- Cysternography Study showed in our patients the characteristics of the Mixed type Pattern: combined ventricular penetration with delayed para-sagittal absorption. Considering the results of the R.H.I.S.A. Studies, that correspond to the P.E.G. -- Contrast Studies, and its invulnerability towards patients, we presume that R.H.I.S.A. may be preferred as a diagnostic tool in Sporadic Huntington Disease.", "contents": "R.H.I.S.A. -- cysternography study in sporadic choreo-athetotic syndrome accompanied with dementia (sporadic Huntington disease). Seven patients who suffered from choreo-athetotic movements, accompanied by slowly progressive mental and affective decline over several years, without hereditary background, were admitted for clinical and psychodiagnostic tests. Laboratory examinations and anamnestic data were negative, and therefore a presumed diagnosis of sporadic Huntington disease was made. In order to verify the diagnosis, we had done P.E.G. -- Contrast study, and R.H.I.S.A. -- Cysternography. The P.E.G. -- Contrast demonstrated an enlargement of the sub-arachnoidal space and a symmetrical enlargement of the ventricular System, that may represent cortical and sub-cortical atrophy. The R.H.I.S.A. -- Cysternography Study showed in our patients the characteristics of the Mixed type Pattern: combined ventricular penetration with delayed para-sagittal absorption. Considering the results of the R.H.I.S.A. Studies, that correspond to the P.E.G. -- Contrast Studies, and its invulnerability towards patients, we presume that R.H.I.S.A. may be preferred as a diagnostic tool in Sporadic Huntington Disease."} {"id": "PMID:162366", "title": "Carcinogenic activity in Sprague-Dawley rats of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-gluco-pyranose (chlorozotocin).", "content": "Sprague--Dawley rats of both sexes received 2 mg/kg body wt (group 1) or 0.4 mg/kg body wt (group 2) of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) intraperitoneally in weekly injections for life. A dose-dependent carcinogenic effect of chlorozotocin was found (animals with malignant tumors in group 1: males 88%, females 89%, in group 2: males 83%, females 63%, in controls: males 10%, females 24%). Chlorozotocin reduced the life expectancy of treated animals significantly, compared to solvent controls. Histologically, the chlorozotocin-induced tumors were shown to be mesotheliomas or sarcomas of the peritoneal cavity (undifferentiated type, fibrosarcomas, myosarcomas).", "contents": "Carcinogenic activity in Sprague-Dawley rats of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-gluco-pyranose (chlorozotocin). Sprague--Dawley rats of both sexes received 2 mg/kg body wt (group 1) or 0.4 mg/kg body wt (group 2) of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) intraperitoneally in weekly injections for life. A dose-dependent carcinogenic effect of chlorozotocin was found (animals with malignant tumors in group 1: males 88%, females 89%, in group 2: males 83%, females 63%, in controls: males 10%, females 24%). Chlorozotocin reduced the life expectancy of treated animals significantly, compared to solvent controls. Histologically, the chlorozotocin-induced tumors were shown to be mesotheliomas or sarcomas of the peritoneal cavity (undifferentiated type, fibrosarcomas, myosarcomas)."} {"id": "PMID:162367", "title": "The fate of [14C]streptozotocin in nicotinamide-pretreated mice: observations on pancreatic islet radioactivity and urinary N1-methyl-14C]nicotinamide-excretion.", "content": "A high labelling of the pancreatic islets was found 3 and 24 h after a diabetogenic dose of [14C]streptozotocin to mice in which the acids islet injury had been prevented by nicotinamide-pretreatment. In non-pretreated [14C]streptozotocin-injected mice, a much lower radioactivity was observed in the pancreatic islets; at 3 h and at 24 h, there was no detectable radioactivity in the islets. No evidence was found to indicate that nicotinamide-pretreatment had any marked effect on the uptake or retention of radioactivity in other tissues. N1-[methyl-14C]nicotinamide was not found in the urine of non-pretreated [14C]streptozotocin-injected mice. When the animals were pretreated with nicotinamide, N1-[methyl-14C]nicotinamide was detected in the urine, but this represented only a small fraction of the injected radioactivity and of the excreted N1-methylnicotinamide. This result does not support the hypothesis that the disturbance of the NAD-metabolism, which streptozotocin causes, is due to a methylation of nicotinamide.", "contents": "The fate of [14C]streptozotocin in nicotinamide-pretreated mice: observations on pancreatic islet radioactivity and urinary N1-methyl-14C]nicotinamide-excretion. A high labelling of the pancreatic islets was found 3 and 24 h after a diabetogenic dose of [14C]streptozotocin to mice in which the acids islet injury had been prevented by nicotinamide-pretreatment. In non-pretreated [14C]streptozotocin-injected mice, a much lower radioactivity was observed in the pancreatic islets; at 3 h and at 24 h, there was no detectable radioactivity in the islets. No evidence was found to indicate that nicotinamide-pretreatment had any marked effect on the uptake or retention of radioactivity in other tissues. N1-[methyl-14C]nicotinamide was not found in the urine of non-pretreated [14C]streptozotocin-injected mice. When the animals were pretreated with nicotinamide, N1-[methyl-14C]nicotinamide was detected in the urine, but this represented only a small fraction of the injected radioactivity and of the excreted N1-methylnicotinamide. This result does not support the hypothesis that the disturbance of the NAD-metabolism, which streptozotocin causes, is due to a methylation of nicotinamide."} {"id": "PMID:162423", "title": "[Circulating immune complexes in patients with malignant diseases].", "content": "Circulating immune complexes were determined by a solid phase C1q assay in patients with divers malignancies. In Hodgkin's disease (n = 20), immune complexes were detected only in two patients during chemotherapy. Both patients succumbed shortly thereafter. In patients with testicular malignancies (n = 18), immune complexes were detected especially in patients without evidence of metastatic disease. Sequential investigations did not reveal prognostic insights. Summing up these data and the data obtained in additional patients with malignancies, it is interesting to note, that patients with carcinomas have a significant higher incidence of circulating immune complexes with malignancies of the lymphatic system. Our data, however, do not exclude presence of other than C1q binding immune complexes.", "contents": "[Circulating immune complexes in patients with malignant diseases]. Circulating immune complexes were determined by a solid phase C1q assay in patients with divers malignancies. In Hodgkin's disease (n = 20), immune complexes were detected only in two patients during chemotherapy. Both patients succumbed shortly thereafter. In patients with testicular malignancies (n = 18), immune complexes were detected especially in patients without evidence of metastatic disease. Sequential investigations did not reveal prognostic insights. Summing up these data and the data obtained in additional patients with malignancies, it is interesting to note, that patients with carcinomas have a significant higher incidence of circulating immune complexes with malignancies of the lymphatic system. Our data, however, do not exclude presence of other than C1q binding immune complexes."} {"id": "PMID:162424", "title": "[A new insulin radioimmunotest and its use in the determination of anti-insulin antibodies].", "content": "Acetylation of insulin with 3H-acetic anhydride resulted in the predominant 3H-labeling at the aminoterminal position of the B-chain (B1). The labeled insulin was unchanged in its immunologic reactivity as compared to native insulin. It was used in a second antibody radioimmunoassay for the detection of antiinsulin-antibodies in insulin-dependent patients with Diabetes mellitus.", "contents": "[A new insulin radioimmunotest and its use in the determination of anti-insulin antibodies]. Acetylation of insulin with 3H-acetic anhydride resulted in the predominant 3H-labeling at the aminoterminal position of the B-chain (B1). The labeled insulin was unchanged in its immunologic reactivity as compared to native insulin. It was used in a second antibody radioimmunoassay for the detection of antiinsulin-antibodies in insulin-dependent patients with Diabetes mellitus."} {"id": "PMID:162432", "title": "[P wave analysis for the electrocardiographic diagnosis of left ventricular hypertrophy. A study of a population with arterial hypertension (author's transl)].", "content": "The electrocardiogram of 100 normal subjects and 216 patients with arterial hypertension in different stages have been analysed. P wave especially has been taken into consideration: it is often abnormal in the presence of left ventricular hypertrophy (LVI). The point-score system elaborated by Romhilt and Estes allows, if only QRS-T is considered, to diagnose LVI in 32 of the hypertensive patients (15%) and in 41 cases (19%) if the increase of P wave terminal forces is emphasized. Nevertheless this P wave characteristic does not appear more useful than others (axis less than or equal to 40 degrees; duration greater than or equal to 0.12 sec; presence of notch). The best results are achieved by considering the coexistence of two or more abnormalities of the P wave. Thus LVI is diagnosed in 52 (24%) of our cases, without false positive.", "contents": "[P wave analysis for the electrocardiographic diagnosis of left ventricular hypertrophy. A study of a population with arterial hypertension (author's transl)]. The electrocardiogram of 100 normal subjects and 216 patients with arterial hypertension in different stages have been analysed. P wave especially has been taken into consideration: it is often abnormal in the presence of left ventricular hypertrophy (LVI). The point-score system elaborated by Romhilt and Estes allows, if only QRS-T is considered, to diagnose LVI in 32 of the hypertensive patients (15%) and in 41 cases (19%) if the increase of P wave terminal forces is emphasized. Nevertheless this P wave characteristic does not appear more useful than others (axis less than or equal to 40 degrees; duration greater than or equal to 0.12 sec; presence of notch). The best results are achieved by considering the coexistence of two or more abnormalities of the P wave. Thus LVI is diagnosed in 52 (24%) of our cases, without false positive."} {"id": "PMID:162434", "title": "Correlated effects of cigarette smoke components on alveolar macrophage adenosine triphosphatase activity and phagocytosis.", "content": "An initial examination was made of the hypothesis that one action of cigarette smoke components on pulmonary alveolar macrophage function involves the inhibition of contractile protein adenosine triphosphatase activity. Pulmonary alveolar macrophage calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, sodium-potassium-dependent adenosine triphosphatase activity, phagocytosis, and cell adhesiveness were measured in the presence of cigarette smoke, acrolein, ouabain, and ethacrynic acid. Calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, phagocytosis, and adhesiveness were inhibited by smoke and ethacrynic acid, but not by ouabain. Acrolein, a component of smoke, inhibited phagocytosis, adhesiveness, and calcium-dependent adenosine triphosphatase activity, indicating that another component of smoke must be effective at inhibiting magnesium-dependent adenosine triphosphatase activity. Sodium-potassium-dependent adenosine triphosphatase activity was inhibited by ouabain and ethacrynic acid, but not by smoke or acrolein. Finally, sulfhydryl reagents at least partially protected the macrophages against the inhibitory actions of each of the agents. The results are in accord with recently obtained experimental evidence that calcium-dependent adenosine triphosphatase and, perhaps, magnesium-dependent adenosine triphosphatase play a role in phagocytosis. The data also suggest that smoke components affect a number of macrophage activities, including adhesion and phagocytosis, by altering the cell's contractile apparatus.", "contents": "Correlated effects of cigarette smoke components on alveolar macrophage adenosine triphosphatase activity and phagocytosis. An initial examination was made of the hypothesis that one action of cigarette smoke components on pulmonary alveolar macrophage function involves the inhibition of contractile protein adenosine triphosphatase activity. Pulmonary alveolar macrophage calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, sodium-potassium-dependent adenosine triphosphatase activity, phagocytosis, and cell adhesiveness were measured in the presence of cigarette smoke, acrolein, ouabain, and ethacrynic acid. Calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, phagocytosis, and adhesiveness were inhibited by smoke and ethacrynic acid, but not by ouabain. Acrolein, a component of smoke, inhibited phagocytosis, adhesiveness, and calcium-dependent adenosine triphosphatase activity, indicating that another component of smoke must be effective at inhibiting magnesium-dependent adenosine triphosphatase activity. Sodium-potassium-dependent adenosine triphosphatase activity was inhibited by ouabain and ethacrynic acid, but not by smoke or acrolein. Finally, sulfhydryl reagents at least partially protected the macrophages against the inhibitory actions of each of the agents. The results are in accord with recently obtained experimental evidence that calcium-dependent adenosine triphosphatase and, perhaps, magnesium-dependent adenosine triphosphatase play a role in phagocytosis. The data also suggest that smoke components affect a number of macrophage activities, including adhesion and phagocytosis, by altering the cell's contractile apparatus."} {"id": "PMID:162438", "title": "Erythrocyte enzyme deficiencies assessed with a miniature centrifugal analyzer.", "content": "Methods for assaying 16 erythrocyte enzymes have been adapted to the miniature centrifugal analyzer. Less than 15 micro L of whole blood is required for all 16 assays. Variation attributable to temporal effects, rotor effects, and random residual error is minor. Initial population studies of blood from adults and cord-blood samples suggest a CV of less than 12% for 12 of the 16 enzymes; thus it should be possible to identify the heterozygous deficient individual. Preliminary data suggest that three such individuals, with enzyme activity (adenylate kinase, pyruvate kinase, phosphoglycerate kinase) about half the expected, have been identified, as well as two individuals deficient in glucose-6-phosphate dehydrogenase.", "contents": "Erythrocyte enzyme deficiencies assessed with a miniature centrifugal analyzer. Methods for assaying 16 erythrocyte enzymes have been adapted to the miniature centrifugal analyzer. Less than 15 micro L of whole blood is required for all 16 assays. Variation attributable to temporal effects, rotor effects, and random residual error is minor. Initial population studies of blood from adults and cord-blood samples suggest a CV of less than 12% for 12 of the 16 enzymes; thus it should be possible to identify the heterozygous deficient individual. Preliminary data suggest that three such individuals, with enzyme activity (adenylate kinase, pyruvate kinase, phosphoglycerate kinase) about half the expected, have been identified, as well as two individuals deficient in glucose-6-phosphate dehydrogenase."} {"id": "PMID:162440", "title": "Psychiatric liaison nurse for neurosurgery: an innovative approach to management of chronic pain.", "content": "A fundamental aim of the Neurosurgical Unit at Georgia Baptist Medical Center is to enable each individual to return to normal and meaningful functioning. The problem of chronic pain almost always results in a steady decrease in those activities, interests, and concerns which are essential to the normal process of living. When the process is disrupted, the result is usually a feeling of despair and uselessness. These problems will almost inevitably complicate the pain experience. In addition, the ever present stress that accompanies severe and chronic problems of any sort tends to result in related psychological difficulties such as depression, anxiety, feelings of inadequacy and a multitude of other family and personal problems. These difficulties often become major features of an individual's pain problem. A holistic approach to patient care is based on the concept that each individual needs to be considered physically, psychologically and spiritually. The active participation of the psychiatric liaison nurse as a member of the neurosurgical team helps integrate the forces that enable such an approach. By focusing on a thorough patient assessment, improved staff morale and improved well being of patients, the psychiatric liaison nurse assists the team in focusing its energy on total comprehensive patient care. The combination of clinical neurosurgical treatment and psychological care has proven effective in helping our neurosurgical team achieve the fundamental goal toward which we all work.", "contents": "Psychiatric liaison nurse for neurosurgery: an innovative approach to management of chronic pain. A fundamental aim of the Neurosurgical Unit at Georgia Baptist Medical Center is to enable each individual to return to normal and meaningful functioning. The problem of chronic pain almost always results in a steady decrease in those activities, interests, and concerns which are essential to the normal process of living. When the process is disrupted, the result is usually a feeling of despair and uselessness. These problems will almost inevitably complicate the pain experience. In addition, the ever present stress that accompanies severe and chronic problems of any sort tends to result in related psychological difficulties such as depression, anxiety, feelings of inadequacy and a multitude of other family and personal problems. These difficulties often become major features of an individual's pain problem. A holistic approach to patient care is based on the concept that each individual needs to be considered physically, psychologically and spiritually. The active participation of the psychiatric liaison nurse as a member of the neurosurgical team helps integrate the forces that enable such an approach. By focusing on a thorough patient assessment, improved staff morale and improved well being of patients, the psychiatric liaison nurse assists the team in focusing its energy on total comprehensive patient care. The combination of clinical neurosurgical treatment and psychological care has proven effective in helping our neurosurgical team achieve the fundamental goal toward which we all work."} {"id": "PMID:162444", "title": "[Acute neurogenic pulmonary edema].", "content": "A case of acute pulmonary edema after subarachnoid hemorrhage is presented. A supra and infratentorial arteriovenous malformation was revealed by serial cerebral angiography. Sequential chest films documented regression of both, pulmonary edema and cardiac enlargment. The literature is reviewed and a possible physiopathology is discussed.", "contents": "[Acute neurogenic pulmonary edema]. A case of acute pulmonary edema after subarachnoid hemorrhage is presented. A supra and infratentorial arteriovenous malformation was revealed by serial cerebral angiography. Sequential chest films documented regression of both, pulmonary edema and cardiac enlargment. The literature is reviewed and a possible physiopathology is discussed."} {"id": "PMID:162442", "title": "[Vectorcardiographic findings in atrial enlargement].", "content": "Rational interpretation of changes of the P loop, due to atrial enlargements, must be based on the magnitude and spatial orientation of the main resulting vectors of the atrial activation phenomenon. Under normal conditions, these ones give origin to a mean vector oriented to the left, downward and slightly forward. Right atrial enlargement can be recognized by P loops of more than 100 mcv. The main axis of the elongated PF is comprised between + 60 degrees and + 90 degrees; that of the open PH between + 70 degrees and + 80 degrees and that of PS is located around + 135 degrees. Left atrial enlargement can be diagnosed by a characteristic box glove configuration of the PF loop as well as by an eight-shaped PH. In some cases, the PS loop also becomes eight-shaped. Biatrial enlargement gives rise to slurrings and notchings of the distal portion of the PF loop, a diphasic aspect and frequently an eight-shaped configuration of the PH loop and a triangular morphology of PS, whose base lasts 30 msec. or more.", "contents": "[Vectorcardiographic findings in atrial enlargement]. Rational interpretation of changes of the P loop, due to atrial enlargements, must be based on the magnitude and spatial orientation of the main resulting vectors of the atrial activation phenomenon. Under normal conditions, these ones give origin to a mean vector oriented to the left, downward and slightly forward. Right atrial enlargement can be recognized by P loops of more than 100 mcv. The main axis of the elongated PF is comprised between + 60 degrees and + 90 degrees; that of the open PH between + 70 degrees and + 80 degrees and that of PS is located around + 135 degrees. Left atrial enlargement can be diagnosed by a characteristic box glove configuration of the PF loop as well as by an eight-shaped PH. In some cases, the PS loop also becomes eight-shaped. Biatrial enlargement gives rise to slurrings and notchings of the distal portion of the PF loop, a diphasic aspect and frequently an eight-shaped configuration of the PH loop and a triangular morphology of PS, whose base lasts 30 msec. or more."} {"id": "PMID:162447", "title": "Bend propagation in flagella. II. Incorporation of dynein cross-bridge kinetics into the equations of motion.", "content": "The cross-bridge formalism of T. Hill has been incorporated into the nonlinear differential equations describing planar flagellar motion in an external viscous medium. A stable numerical procedure for solution of these equations is presented. A self-consistent two-state diagram with curvature-dependent rate functions is sufficient to generate stable propagating waves with frequencies and amplitudes typical of sperm flagella. For a particular choice of attachment and detachment rate functions, reasonable variation of frequency and wave speed with increasing viscosity is also obtained. The method can easily be extended to study more realistic state diagrams.", "contents": "Bend propagation in flagella. II. Incorporation of dynein cross-bridge kinetics into the equations of motion. The cross-bridge formalism of T. Hill has been incorporated into the nonlinear differential equations describing planar flagellar motion in an external viscous medium. A stable numerical procedure for solution of these equations is presented. A self-consistent two-state diagram with curvature-dependent rate functions is sufficient to generate stable propagating waves with frequencies and amplitudes typical of sperm flagella. For a particular choice of attachment and detachment rate functions, reasonable variation of frequency and wave speed with increasing viscosity is also obtained. The method can easily be extended to study more realistic state diagrams."} {"id": "PMID:162448", "title": "Zeaxanthin ([3R,3'R]-beta, beta-carotene-3-3'diol) as a resonance Raman and visible absorption probe of membrane structure.", "content": "When zeaxanthin ([3R,3R']-beta, beta-carotene-3,3'diol) is inserted into phospholipid dispersions and the latter heated through their gel-liquid crystal phase transitions, large changes are noted in the resonance Raman and absorption spectra of the carotenoid molecule. By analogy with the data of Carey and co-workers (J. Raman Spectrosc. 6:282) who studied the aggregation of zeaxanthin in acetone-water solutions, it is suggested that the carotenoid aggregates in the phospholipid gel state while forming a monomer in liquid crystal phases. The alterations in both the visible absorption and resonance Raman data have been used to monitor phospholipid phase behavior in dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine, (DSPC) one-component systems and binary mixtures. The phase diagram obtained for the binary system, as constructed from visible absorption and resonance Raman data, is compared with that of Shimshick and McConnell (Biochemistry. 12:2351) obtained from electron spin resonance (ESR) studies. Although the agreement between absorption and ESR data is generally satisfactory, onset temperatures for phase separation at low DSPC mole fractions deduced from resonance Raman measurements are several degrees lower than those from the other methods. Nevertheless, the use of zeaxanthin as a resonance Raman and visible absorption probe behavior will be useful in some situations where ordinary Raman spectroscopic data cannot be obtained easily. The advantage of the resonance Raman approach is illustrated in a study of the phase behavior of a phospholipid extract of a cel- mutant of Neurospora crassa. A phase separation region is observed with onset and completion temperatures of -19 and -6 degrees C, respectively.", "contents": "Zeaxanthin ([3R,3'R]-beta, beta-carotene-3-3'diol) as a resonance Raman and visible absorption probe of membrane structure. When zeaxanthin ([3R,3R']-beta, beta-carotene-3,3'diol) is inserted into phospholipid dispersions and the latter heated through their gel-liquid crystal phase transitions, large changes are noted in the resonance Raman and absorption spectra of the carotenoid molecule. By analogy with the data of Carey and co-workers (J. Raman Spectrosc. 6:282) who studied the aggregation of zeaxanthin in acetone-water solutions, it is suggested that the carotenoid aggregates in the phospholipid gel state while forming a monomer in liquid crystal phases. The alterations in both the visible absorption and resonance Raman data have been used to monitor phospholipid phase behavior in dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine, (DSPC) one-component systems and binary mixtures. The phase diagram obtained for the binary system, as constructed from visible absorption and resonance Raman data, is compared with that of Shimshick and McConnell (Biochemistry. 12:2351) obtained from electron spin resonance (ESR) studies. Although the agreement between absorption and ESR data is generally satisfactory, onset temperatures for phase separation at low DSPC mole fractions deduced from resonance Raman measurements are several degrees lower than those from the other methods. Nevertheless, the use of zeaxanthin as a resonance Raman and visible absorption probe behavior will be useful in some situations where ordinary Raman spectroscopic data cannot be obtained easily. The advantage of the resonance Raman approach is illustrated in a study of the phase behavior of a phospholipid extract of a cel- mutant of Neurospora crassa. A phase separation region is observed with onset and completion temperatures of -19 and -6 degrees C, respectively."} {"id": "PMID:162449", "title": "Inhibition of the humoral response by spleen cells from cyclophosphamide-treated mice.", "content": "Spleen cells obtained from mice injected with cyclophosphamide (200 mg/kg body weight) suppressed the secondary IgG antibody response of memory cells to a T-dependent antigen, DNP-HGG, in Millipore diffusion chambers. Significant suppression (greater than 50%) was found from 5 to 14 days following cyclophosphamide treatment, with peak suppression (86%) on day 7. The primary IgM antibody response to DNP-Ficoll, a T-independent antigen, was not suppressed by these cells. In contrast, suppression was observed in the primary IgM response to sheep red blood cells, a T-dependent antigen. In addition, treatment of the suppressor cell population with anti-Thy-1 serum and complement did not inhibit suppressor activity. We concluded that the suppressor activity was not attributable to a typical T cell, and that the target of suppression was not a B cell. Preliminary evidence suggests that the suppressor activity is regulated, directly or indirectly, by a T cell.", "contents": "Inhibition of the humoral response by spleen cells from cyclophosphamide-treated mice. Spleen cells obtained from mice injected with cyclophosphamide (200 mg/kg body weight) suppressed the secondary IgG antibody response of memory cells to a T-dependent antigen, DNP-HGG, in Millipore diffusion chambers. Significant suppression (greater than 50%) was found from 5 to 14 days following cyclophosphamide treatment, with peak suppression (86%) on day 7. The primary IgM antibody response to DNP-Ficoll, a T-independent antigen, was not suppressed by these cells. In contrast, suppression was observed in the primary IgM response to sheep red blood cells, a T-dependent antigen. In addition, treatment of the suppressor cell population with anti-Thy-1 serum and complement did not inhibit suppressor activity. We concluded that the suppressor activity was not attributable to a typical T cell, and that the target of suppression was not a B cell. Preliminary evidence suggests that the suppressor activity is regulated, directly or indirectly, by a T cell."} {"id": "PMID:162452", "title": "Initial experience with transluminal recanalization of the recently occluded infarct-related coronary artery in acute myocardial infarction -- comparison with conventionally treated patients.", "content": "In 7 patients, the recently occluded infarct-related vessel was recanalized by transluminal catheter techniques during acute myocardial infarction (Group A). 4 patients had single-vessel disease, 2 patients two-vessels disease and one, involvement of three vessels. Control angiography was performed in 6 patients, 8 days to 7 months later. Changes of coronary artery anatomy and left ventricular function were compared with a group of 9 conventionally treated patients, who were found to have occlusion of the infarct-related vessel in the acute stage (Group B). Five Group B patients had one-vessel disease, 3 patients two-vessel disease and 1 patient, involvement of all three vessels. In the chronic stage, all transluminally recanalized vessels were found to be patent in Group A. There was spontaneous recanalization of the infarct vessel in 4 of 9 Group B patients. In Group A, the length of the akinetic segment (AKS) decreased significantly (p less than 0.05) from 145.4 +/- 48.5 mm to 73.2 +/- 73.4 mm (mean +/- SD). Volume parameters did not change significantly. In Group B, length of the AKS did not change significantly, EDVI increased significantly from 81.1 +/- 19.8 to 106.8 +/- 4.6 ml/m2 (p less than 0.05); ESVI increased significantly from 41.7 +/- 13.7; ml/m2 to 66.8 +/- 37.9 ml/m2 (p less than 0.01). In the acute stage, length of the AKS and volume parameters did not differ significantly between the two groups. In the chronic stage, AKS was significantly shorter (A: 73.2 +/- 63.4 mm; 144.9 +/- 59 mm (p less than 0.0025) and EF was significantly higher (A: 54.6 +/- 11.6%; B: 40.9 +/- 14.5% (p less than 0.05) in Group A. Peak CPK was lower in Group A (A: 1009 +/- 827 U/l; B: 1324 +/- 655 U/l), but this difference did not achieve statistical significance. Results of this pilot study suggest that transluminal recanalization in the early phases of acute myocardial infarction might result in limitation of myocardial injury. However, further research will be needed to improve the technique and to test its results.", "contents": "Initial experience with transluminal recanalization of the recently occluded infarct-related coronary artery in acute myocardial infarction -- comparison with conventionally treated patients. In 7 patients, the recently occluded infarct-related vessel was recanalized by transluminal catheter techniques during acute myocardial infarction (Group A). 4 patients had single-vessel disease, 2 patients two-vessels disease and one, involvement of three vessels. Control angiography was performed in 6 patients, 8 days to 7 months later. Changes of coronary artery anatomy and left ventricular function were compared with a group of 9 conventionally treated patients, who were found to have occlusion of the infarct-related vessel in the acute stage (Group B). Five Group B patients had one-vessel disease, 3 patients two-vessel disease and 1 patient, involvement of all three vessels. In the chronic stage, all transluminally recanalized vessels were found to be patent in Group A. There was spontaneous recanalization of the infarct vessel in 4 of 9 Group B patients. In Group A, the length of the akinetic segment (AKS) decreased significantly (p less than 0.05) from 145.4 +/- 48.5 mm to 73.2 +/- 73.4 mm (mean +/- SD). Volume parameters did not change significantly. In Group B, length of the AKS did not change significantly, EDVI increased significantly from 81.1 +/- 19.8 to 106.8 +/- 4.6 ml/m2 (p less than 0.05); ESVI increased significantly from 41.7 +/- 13.7; ml/m2 to 66.8 +/- 37.9 ml/m2 (p less than 0.01). In the acute stage, length of the AKS and volume parameters did not differ significantly between the two groups. In the chronic stage, AKS was significantly shorter (A: 73.2 +/- 63.4 mm; 144.9 +/- 59 mm (p less than 0.0025) and EF was significantly higher (A: 54.6 +/- 11.6%; B: 40.9 +/- 14.5% (p less than 0.05) in Group A. Peak CPK was lower in Group A (A: 1009 +/- 827 U/l; B: 1324 +/- 655 U/l), but this difference did not achieve statistical significance. Results of this pilot study suggest that transluminal recanalization in the early phases of acute myocardial infarction might result in limitation of myocardial injury. However, further research will be needed to improve the technique and to test its results."} {"id": "PMID:162472", "title": "Role of hCG in regulation of the fetal zone of the human fetal adrenal gland.", "content": "It has been suggested that hCG is a trophic hormone for the fetal zone of the human fetal adrenal gland. To test this hypothesis, the isolated fetal zones of adrenals from eight fetuses (12-17-week gestation age) were superfused in the presence or absence of hCG. Dehydroepiandrosterone sulfate (DHAS) was measured in the superfusion effluent. A significant increase in DHAS production was observed in the presence of hCG. DHAS secretion decreased during the first 60 min in the control and experimental superfusions from 83 +/- 10.0 (mean +/- SE) to 71 +/- 8.0, and from 90 +/- 9.0 to 70 +/- 6.0 ng/100 mg/ml, respectively. In the presence of hCG (250 ng/ml), DHAS secretion increased significantly (P less than 0.01) over the controls to 116 +/- 12.0 at 120 min, and remained above the controls thereafter. These results support the hypothesis that hCG is one of the regulators of DHAS production by the human fetal adrenal gland early in gestation. As we found that ACTh stimulated DHAS secretion in a previous study and as there is indirect evidence for a role of ACTH in DHAS regulation late in pregnancy, these observations suggest dual regulation by hCG and ACTH early in pregnancy, and a possible transition to ACTH regulation of the fetal zone of the human fetal adrenal after midgestation.", "contents": "Role of hCG in regulation of the fetal zone of the human fetal adrenal gland. It has been suggested that hCG is a trophic hormone for the fetal zone of the human fetal adrenal gland. To test this hypothesis, the isolated fetal zones of adrenals from eight fetuses (12-17-week gestation age) were superfused in the presence or absence of hCG. Dehydroepiandrosterone sulfate (DHAS) was measured in the superfusion effluent. A significant increase in DHAS production was observed in the presence of hCG. DHAS secretion decreased during the first 60 min in the control and experimental superfusions from 83 +/- 10.0 (mean +/- SE) to 71 +/- 8.0, and from 90 +/- 9.0 to 70 +/- 6.0 ng/100 mg/ml, respectively. In the presence of hCG (250 ng/ml), DHAS secretion increased significantly (P less than 0.01) over the controls to 116 +/- 12.0 at 120 min, and remained above the controls thereafter. These results support the hypothesis that hCG is one of the regulators of DHAS production by the human fetal adrenal gland early in gestation. As we found that ACTh stimulated DHAS secretion in a previous study and as there is indirect evidence for a role of ACTH in DHAS regulation late in pregnancy, these observations suggest dual regulation by hCG and ACTH early in pregnancy, and a possible transition to ACTH regulation of the fetal zone of the human fetal adrenal after midgestation."} {"id": "PMID:162473", "title": "Direct animal and indirect human evidence of altered platelet function in diabetics.", "content": "All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant.", "contents": "Direct animal and indirect human evidence of altered platelet function in diabetics. All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant."} {"id": "PMID:162474", "title": "Augmented venous return: protection of the ischemic myocardium during endotoxemia.", "content": "The effects of gram-negative endotoxin (Escherichia coli 4 mg/kg) induced myocardial failure in the pentobarbital-anesthesized dog were examined by monitoring its influence on coronary and systemic hemodynamics and correlating these results with myofibrillar ATPase activity. An identical series of studies was performed incorporating a femoral-femoral arterial-venous shunt to augment venous return. Over a five-hour period, gram-negative endotoxemia was associated with a progressive fall in arterial pressure, stroke volume, cardiac output, coronary flow, and a rise in total peripheral resistance and diastolic coronary vascular resistance. Augmenting venous return by 313 +/- 71 ml/min significantly increased cardiac output, stroke volume, and coronary flow and substantially reduced total peripheral resistance and coronary vascular resistance. Myofibrillar ATPase activity from both endocardium and epicardium was significantly depressed in the endotoxin-shocked preparations. However, with the augmentation of venous return with the A-V shunt in the endotoxin-treated animal, myofibrillar ATPase activity is normal. It appears that endotoxin causes a decrease both in venous return and in cardiac contractility by increasing total peripheral resistance, coronary vascular resistance, and impedance to left ventricular ejection. Augmenting venous return by optimizing preload and reducing afterload prevents any significant increase in total peripheral resistance, coronary vascular resistance, or impedance to left ventricular ejection. This is manifested by a rise in cardiac output, stroke volume, and coronary flow and the preservation of myocardial function. This is the first successful application of left ventricular afterload reduction in noncardiogenic shock.", "contents": "Augmented venous return: protection of the ischemic myocardium during endotoxemia. The effects of gram-negative endotoxin (Escherichia coli 4 mg/kg) induced myocardial failure in the pentobarbital-anesthesized dog were examined by monitoring its influence on coronary and systemic hemodynamics and correlating these results with myofibrillar ATPase activity. An identical series of studies was performed incorporating a femoral-femoral arterial-venous shunt to augment venous return. Over a five-hour period, gram-negative endotoxemia was associated with a progressive fall in arterial pressure, stroke volume, cardiac output, coronary flow, and a rise in total peripheral resistance and diastolic coronary vascular resistance. Augmenting venous return by 313 +/- 71 ml/min significantly increased cardiac output, stroke volume, and coronary flow and substantially reduced total peripheral resistance and coronary vascular resistance. Myofibrillar ATPase activity from both endocardium and epicardium was significantly depressed in the endotoxin-shocked preparations. However, with the augmentation of venous return with the A-V shunt in the endotoxin-treated animal, myofibrillar ATPase activity is normal. It appears that endotoxin causes a decrease both in venous return and in cardiac contractility by increasing total peripheral resistance, coronary vascular resistance, and impedance to left ventricular ejection. Augmenting venous return by optimizing preload and reducing afterload prevents any significant increase in total peripheral resistance, coronary vascular resistance, or impedance to left ventricular ejection. This is manifested by a rise in cardiac output, stroke volume, and coronary flow and the preservation of myocardial function. This is the first successful application of left ventricular afterload reduction in noncardiogenic shock."} {"id": "PMID:162477", "title": "[Vectorcardiographic manifestations of right ventricular enlargement].", "content": "The basic criteria for the vectorcardiographic diagnosis of right ventricular enlargement are discussed, in context with the course of myocardial activation. Right ventricular dilatation, secondary to isolated diastolic overloading (atrial septal defect) shows basically different degrees of dextrorotation. The ventricular curve starts to the left on the frontal and horizontal planes, and forward on the last one. Cases with right ventricular hypertrophy, produced by sustained systolic overload, are also evaluated. When the hypertrophy is generalized (pulmonary valvular stenosis), there is an increase in the manifestation of all the resulting vectors of activation of this ventricle: IIs, IIr, and IIIr. As a resultant of these changes, the ventricular curve presents a clockwise rotation in the three planes, and is oriented to the right and forward, with its terminal portions generally located above the E point. When the right ventricular hypertrophy is of the segmentary type, there is an increase of the manifestation of only some of the resulting vectors of the activation of this ventricle. For example, the vector IIr will be increased in cases of tetralogy of Fallot, while the IIIr will be increased in some cases of obstructive chronic pulmonary hypertensive cardiopathy. The T loop, of secondary type, generally opposes the vector IIr on the horizontal plane, and the IIIr on the frontal plane. When an important right ventricular dilatation is associated to a right bundle branch block of intermediate degree, owing to their proximity, the manifestation of the electromotive parietal forces is increased at the expense of the septal ones. This phenomenon produces a characteristic appearance of the SH loop, narrow and with a clockwise rotation.", "contents": "[Vectorcardiographic manifestations of right ventricular enlargement]. The basic criteria for the vectorcardiographic diagnosis of right ventricular enlargement are discussed, in context with the course of myocardial activation. Right ventricular dilatation, secondary to isolated diastolic overloading (atrial septal defect) shows basically different degrees of dextrorotation. The ventricular curve starts to the left on the frontal and horizontal planes, and forward on the last one. Cases with right ventricular hypertrophy, produced by sustained systolic overload, are also evaluated. When the hypertrophy is generalized (pulmonary valvular stenosis), there is an increase in the manifestation of all the resulting vectors of activation of this ventricle: IIs, IIr, and IIIr. As a resultant of these changes, the ventricular curve presents a clockwise rotation in the three planes, and is oriented to the right and forward, with its terminal portions generally located above the E point. When the right ventricular hypertrophy is of the segmentary type, there is an increase of the manifestation of only some of the resulting vectors of the activation of this ventricle. For example, the vector IIr will be increased in cases of tetralogy of Fallot, while the IIIr will be increased in some cases of obstructive chronic pulmonary hypertensive cardiopathy. The T loop, of secondary type, generally opposes the vector IIr on the horizontal plane, and the IIIr on the frontal plane. When an important right ventricular dilatation is associated to a right bundle branch block of intermediate degree, owing to their proximity, the manifestation of the electromotive parietal forces is increased at the expense of the septal ones. This phenomenon produces a characteristic appearance of the SH loop, narrow and with a clockwise rotation."} {"id": "PMID:162478", "title": "[Vectorcardiographic manifestations of left ventricular and biventricular enlargement].", "content": "The basic criteria for the vectorcardiographic diagnosis of left ventricular and biventricular enlargements are discussed on the basis of the myocardial activation sequence. Left ventricular dilatation, secondary to isolated diastolic overloading, increases the manifestation of all the vectors resulting of the activation of this ventricle. These changes reflect the proximity of the left ventricular walls to the exploring electrodes. The vectors above mentioned project themselves as wide ventricular curves with counterclockwise rotation on the three planes. The T loop, of secondary type, is concordant in its orientation with the R loop. Cases with left ventricular hypertrophy, produced by a sustained systolic overloading, are also described. In the presence of global left ventricular hypertrophy without LBBB, the manifestation of all the vectors resulting from the depolarization of this ventricle (I, IIl, IIIl), is increased. This is due to a prolonged duration of the corresponding activation fronts. These vectors are projected on the different segments of the ventricular curves and they show a counterclockwise rotation on the three planes. When LBBB is also present, the first septal vector is not evident. The T loop, of secondary type, opposes the R loop on the frontal and horizontal planes. The presence of left ventricular hypertrophy of the segmentary type, generally increases the manifestation of the vector I, and sometimes, also that of the vector IIIl. When both ventricles are hypertrophied, the electromotive forces of the chamber more severely affected predominate in the vectorcardiographic records.", "contents": "[Vectorcardiographic manifestations of left ventricular and biventricular enlargement]. The basic criteria for the vectorcardiographic diagnosis of left ventricular and biventricular enlargements are discussed on the basis of the myocardial activation sequence. Left ventricular dilatation, secondary to isolated diastolic overloading, increases the manifestation of all the vectors resulting of the activation of this ventricle. These changes reflect the proximity of the left ventricular walls to the exploring electrodes. The vectors above mentioned project themselves as wide ventricular curves with counterclockwise rotation on the three planes. The T loop, of secondary type, is concordant in its orientation with the R loop. Cases with left ventricular hypertrophy, produced by a sustained systolic overloading, are also described. In the presence of global left ventricular hypertrophy without LBBB, the manifestation of all the vectors resulting from the depolarization of this ventricle (I, IIl, IIIl), is increased. This is due to a prolonged duration of the corresponding activation fronts. These vectors are projected on the different segments of the ventricular curves and they show a counterclockwise rotation on the three planes. When LBBB is also present, the first septal vector is not evident. The T loop, of secondary type, opposes the R loop on the frontal and horizontal planes. The presence of left ventricular hypertrophy of the segmentary type, generally increases the manifestation of the vector I, and sometimes, also that of the vector IIIl. When both ventricles are hypertrophied, the electromotive forces of the chamber more severely affected predominate in the vectorcardiographic records."} {"id": "PMID:162479", "title": "Isoenzyme characterization of Leishmania spp from Algeria.", "content": "Five Algerian stocks of Leishmania were compared with two stocks from USSR and one from Sudan by means of isoenzyme electrophoresis of two enzymes: glucose-phosphate isomerase (GPI) and phosphoglucomutase (PGM). Three stocks isolated from patients suffering from cutaneous leishmaniasis appeared to be L. tropica major. This correlated well the epidemiological features of the endemic area from where the stocks originated. Two stocks isolated from patients suffering from visceral leishmaniasis appeared to be different from the Sudanese stock of L. donovani.", "contents": "Isoenzyme characterization of Leishmania spp from Algeria. Five Algerian stocks of Leishmania were compared with two stocks from USSR and one from Sudan by means of isoenzyme electrophoresis of two enzymes: glucose-phosphate isomerase (GPI) and phosphoglucomutase (PGM). Three stocks isolated from patients suffering from cutaneous leishmaniasis appeared to be L. tropica major. This correlated well the epidemiological features of the endemic area from where the stocks originated. Two stocks isolated from patients suffering from visceral leishmaniasis appeared to be different from the Sudanese stock of L. donovani."} {"id": "PMID:162485", "title": "Psychosis as a predictor of response to lithium maintenance treatment in bipolar affective disorder.", "content": "Sixty-six bipolar I lithium clinic patients were studied for a history of psychotic symptoms at some time during the course of their illness. Agreement between different sources of information was calculated, and the patient population was divided into psychotic and non-psychotic subgroups. Probability of remaining well on lithium for the different subgroups was analyzed by the life table method. Psychosis during mania appeared to be associated with especially good early lithium prophylaxis.", "contents": "Psychosis as a predictor of response to lithium maintenance treatment in bipolar affective disorder. Sixty-six bipolar I lithium clinic patients were studied for a history of psychotic symptoms at some time during the course of their illness. Agreement between different sources of information was calculated, and the patient population was divided into psychotic and non-psychotic subgroups. Probability of remaining well on lithium for the different subgroups was analyzed by the life table method. Psychosis during mania appeared to be associated with especially good early lithium prophylaxis."} {"id": "PMID:162486", "title": "Assortative mating and affective disorders.", "content": "Seventy-two spouses of subjects with recurrent primary affective disorders (PAD), were investigated for the presence of psychiatric disorders in their lives and in those of their first degree relatives, and compared with 71 spouses of non-psychiatrically ill control subjects. No difference was found in the risk for PAD; on the other hand spouses of affective patients manifested a greater occurrence of psychiatric disorders belonging to the affective spectrum, as did their respective first-degree relatives.", "contents": "Assortative mating and affective disorders. Seventy-two spouses of subjects with recurrent primary affective disorders (PAD), were investigated for the presence of psychiatric disorders in their lives and in those of their first degree relatives, and compared with 71 spouses of non-psychiatrically ill control subjects. No difference was found in the risk for PAD; on the other hand spouses of affective patients manifested a greater occurrence of psychiatric disorders belonging to the affective spectrum, as did their respective first-degree relatives."} {"id": "PMID:162487", "title": "Detecting depressive disorders in drug abusers: a comparison of screening instruments.", "content": "Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression.", "contents": "Detecting depressive disorders in drug abusers: a comparison of screening instruments. Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression."} {"id": "PMID:162488", "title": "Depressive symptoms in rape victims.", "content": "Thirty-four recent rape victims were assessed for depressive symptomatology using a well-validated self-report instrument in combination with formal psychiatric evaluation. Fifteen subjects were found to be moderately or severely depressed when measured on the self-report questionnaire. A closer examination of these 15 subjects revealed that 8 were suffering from a major depressive disorder. The authors emphasize that all clinicians working with rape victims should be alert to the emergence of depression in this population.", "contents": "Depressive symptoms in rape victims. Thirty-four recent rape victims were assessed for depressive symptomatology using a well-validated self-report instrument in combination with formal psychiatric evaluation. Fifteen subjects were found to be moderately or severely depressed when measured on the self-report questionnaire. A closer examination of these 15 subjects revealed that 8 were suffering from a major depressive disorder. The authors emphasize that all clinicians working with rape victims should be alert to the emergence of depression in this population."} {"id": "PMID:162489", "title": "The familial prevalence in second-degree relatives of patients with anxiety neurosis (panic disorder).", "content": "A family history study of second-degree relatives of 19 patients with anxiety neurosis (panic disorder) and 19 controls showed a morbidity risk of 9.5% among the former compared with 1.4% among the latter. These risks were approximately half those found among first-degree relatives. Female relatives were at higher risk for anxiety neurosis. The risk for other psychiatric illnesses did not differ between the relatives of anxiety neurosis and controls.", "contents": "The familial prevalence in second-degree relatives of patients with anxiety neurosis (panic disorder). A family history study of second-degree relatives of 19 patients with anxiety neurosis (panic disorder) and 19 controls showed a morbidity risk of 9.5% among the former compared with 1.4% among the latter. These risks were approximately half those found among first-degree relatives. Female relatives were at higher risk for anxiety neurosis. The risk for other psychiatric illnesses did not differ between the relatives of anxiety neurosis and controls."} {"id": "PMID:162490", "title": "Distribution of ancestral secondary cases in anxiety neurosis (panic disorder).", "content": "The Slater computational model for use in distinguishing between polygenic inheritance and the effects of a single dominant gene with incomplete penetrance was applied to 15 kindreds of anxiety neurosis (panic disorder). The number of observed unilateral pairs (two ancestral cases from one side of the kindred) was significantly greater than the number expected. Therefore, these results suggest a dominant mode of transmission for anxiety neurosis.", "contents": "Distribution of ancestral secondary cases in anxiety neurosis (panic disorder). The Slater computational model for use in distinguishing between polygenic inheritance and the effects of a single dominant gene with incomplete penetrance was applied to 15 kindreds of anxiety neurosis (panic disorder). The number of observed unilateral pairs (two ancestral cases from one side of the kindred) was significantly greater than the number expected. Therefore, these results suggest a dominant mode of transmission for anxiety neurosis."} {"id": "PMID:162493", "title": "The relationship of family history of alcoholism to primary affective disorder.", "content": "One hundred sixty-eight patients with primary affective disorder were studied regarding history of alcohol-related problems. Alcohol-related problems were identified in 19 patients. We found that the morbid risk for alcoholism was significantly increased among relatives of male patients with drinking problems as compared to relatives of male patients without drinking problems. Our data suggest that psychiatric illness in relatives of probands with severe bipolar illness tends to be affective disorder tends to include alcoholism plus affective disorder.", "contents": "The relationship of family history of alcoholism to primary affective disorder. One hundred sixty-eight patients with primary affective disorder were studied regarding history of alcohol-related problems. Alcohol-related problems were identified in 19 patients. We found that the morbid risk for alcoholism was significantly increased among relatives of male patients with drinking problems as compared to relatives of male patients without drinking problems. Our data suggest that psychiatric illness in relatives of probands with severe bipolar illness tends to be affective disorder tends to include alcoholism plus affective disorder."} {"id": "PMID:162494", "title": "Treatment of unipolar depression following electroconvulsive therapy. Relapse rate comparisons between lithium and tricyclics therapies following ECT.", "content": "A restrospective chart study and follow-up telephone interviews were used to compare the relapse rates of unipolar depressives who had received either lithium or tricyclics following ECT. The results showed no difference between the two treatment groups. The literature on ECT was reviewed in the light of the results from the present study. We concluded that ECT followed by either lithium or a tricyclic antidepressant is a more effective treatment for unipolar depression than ECT alone.", "contents": "Treatment of unipolar depression following electroconvulsive therapy. Relapse rate comparisons between lithium and tricyclics therapies following ECT. A restrospective chart study and follow-up telephone interviews were used to compare the relapse rates of unipolar depressives who had received either lithium or tricyclics following ECT. The results showed no difference between the two treatment groups. The literature on ECT was reviewed in the light of the results from the present study. We concluded that ECT followed by either lithium or a tricyclic antidepressant is a more effective treatment for unipolar depression than ECT alone."} {"id": "PMID:162495", "title": "Schizoaffective disorders. Results of a genetic investigation, I.", "content": "1004 first degree relatives fo 150 schizoaffective patients (41 males, 109 females) were studied and a total morbidity risk of 29.6% of schizoaffective spectrum disorders were found. The relatives show an increased morbidity risk for schizophrenia (5.26%) and affective disorder (6.55%) with a high incidence of catatonia and unipolar depression; schizoaffective secondary cases were only found in 3%. There is no significant difference in morbidity between parents, siblings and children. The morbidity risk of neuroses is 5.3%, for personality disorders 7.2% and for suicides without spectrum diagnosis 1.8%. Off-spring of affected parents show a morbidity risk twice as high as that of off-spring of non-affected parents. The findings do not support the present concept of the ICD (International Classification of Disorders) of WHO, which subsumes schizoaffective disorders under the major rubric of schizophrenia. From a genetic viewpoint schizoaffective disorder takes an intermediate position between schizophrenia and affective disorders. None of the present hypotheses of the mode of inheritance is supported by the findings.", "contents": "Schizoaffective disorders. Results of a genetic investigation, I. 1004 first degree relatives fo 150 schizoaffective patients (41 males, 109 females) were studied and a total morbidity risk of 29.6% of schizoaffective spectrum disorders were found. The relatives show an increased morbidity risk for schizophrenia (5.26%) and affective disorder (6.55%) with a high incidence of catatonia and unipolar depression; schizoaffective secondary cases were only found in 3%. There is no significant difference in morbidity between parents, siblings and children. The morbidity risk of neuroses is 5.3%, for personality disorders 7.2% and for suicides without spectrum diagnosis 1.8%. Off-spring of affected parents show a morbidity risk twice as high as that of off-spring of non-affected parents. The findings do not support the present concept of the ICD (International Classification of Disorders) of WHO, which subsumes schizoaffective disorders under the major rubric of schizophrenia. From a genetic viewpoint schizoaffective disorder takes an intermediate position between schizophrenia and affective disorders. None of the present hypotheses of the mode of inheritance is supported by the findings."} {"id": "PMID:162496", "title": "Are schizoaffective psychoses heterogeneous? Results of a genetic investigation, II.", "content": "150 schizoaffective probands and their 1029 first-degree relatives were examined in search of the heterogeneity of the disorder. The sample of probands was split by several criteria. Among the various subgroups the morbidity risk of relatives was analysed as an external criterion for heterogeneity. Female relatives show a higher risk for affective disorders that male relatives. This is true for relatives of male and female index patients. Schizophrenia is equally frequent in male and female relatives. Schizoaffective psychoses take an intermediate position. The further analysis included the following characteristics of the probands: age at first episode, number of episodes, psychopathological subtypes (affective, schizophrenic, undifferentiated: manic, non-manic). None of these criteria proved to distinguish subgroups significantly, therefore, the search for heterogeneity was negative, although some results show a trend to the expected direction.", "contents": "Are schizoaffective psychoses heterogeneous? Results of a genetic investigation, II. 150 schizoaffective probands and their 1029 first-degree relatives were examined in search of the heterogeneity of the disorder. The sample of probands was split by several criteria. Among the various subgroups the morbidity risk of relatives was analysed as an external criterion for heterogeneity. Female relatives show a higher risk for affective disorders that male relatives. This is true for relatives of male and female index patients. Schizophrenia is equally frequent in male and female relatives. Schizoaffective psychoses take an intermediate position. The further analysis included the following characteristics of the probands: age at first episode, number of episodes, psychopathological subtypes (affective, schizophrenic, undifferentiated: manic, non-manic). None of these criteria proved to distinguish subgroups significantly, therefore, the search for heterogeneity was negative, although some results show a trend to the expected direction."} {"id": "PMID:162497", "title": "Affect and the menstrual cycle.", "content": "Evidence from both retrospective and prospective studies suggests that many women do show cyclical changes in affect. Negative changes such as irritability, headache, tension, anxiety, sleep disturbance and depression are more frequent in the premenstrual and menstrual phases. Positive changes, pleasantness, increased vigour and elation are reported more often in the follicular or mid-cycle phases. Various theories have been suggested to explain these changes. These include psychodynamic, sociological and biological explanations. Although there is some evidence to support each theory no definite conclusions can be reached about the aetiological basis of most affective changes. Interpretation of studies attempting to link hormonal and affective fluctuations in limited by the many methodological problems outlined. Only one study appeared able to conclusively demonstrate a hormonal basis for a cyclical symptom. Suggestions are made for further research in this area.", "contents": "Affect and the menstrual cycle. Evidence from both retrospective and prospective studies suggests that many women do show cyclical changes in affect. Negative changes such as irritability, headache, tension, anxiety, sleep disturbance and depression are more frequent in the premenstrual and menstrual phases. Positive changes, pleasantness, increased vigour and elation are reported more often in the follicular or mid-cycle phases. Various theories have been suggested to explain these changes. These include psychodynamic, sociological and biological explanations. Although there is some evidence to support each theory no definite conclusions can be reached about the aetiological basis of most affective changes. Interpretation of studies attempting to link hormonal and affective fluctuations in limited by the many methodological problems outlined. Only one study appeared able to conclusively demonstrate a hormonal basis for a cyclical symptom. Suggestions are made for further research in this area."} {"id": "PMID:162498", "title": "Relationship between mood changes and adrenal cortical activity in a patient with 48-hour unipolar-depressive cycles.", "content": "A 66-year-old patient with 48-hour unipolar-depressive cycles was studied in the hospital for one month and in an isolation unit for two weeks. At 3-hour intervals during the day and once at night the mood state was assessed by two self-rating scales and urine was collected for the determination of urinary free cortisol (UFC). In the hospital there was a regular alternation between 'good' and 'bad' days. Without exception the switch from normal to depressive mood occurred between 22:00 and 2:30, when the patient was sleeping. The switch from depressive to good mood was variable and occurred in the late morning or in the afternoon. On a 24-hour basis a highly significant correlation was seen between the mood state and the UFC excretion: r = 0.73, P less than 0.001 (hospital); r = 0.82, P less than 0.01 (isolation unit). The shape of the 24-hour profile for the UFC excretion was similar on good and bad days, with a maximum between 2:30 and 7:00 and a minimum between 19:00 and 2:30. However, on bad days UFC was elevated at all clock times. A decrease in adrenal cortical activity preceded or was parallel to substantial improvement in the mood state. Internal desynchronization occurred in the isolation unit but not in the hospital, with a rest-activity period of 18.6 h and a period close to 24 h for UFC excretion. Changes in mood were associated with both cycles, and a very close link between the switch from normal to depressive mood and the sleep state could be demonstrated.", "contents": "Relationship between mood changes and adrenal cortical activity in a patient with 48-hour unipolar-depressive cycles. A 66-year-old patient with 48-hour unipolar-depressive cycles was studied in the hospital for one month and in an isolation unit for two weeks. At 3-hour intervals during the day and once at night the mood state was assessed by two self-rating scales and urine was collected for the determination of urinary free cortisol (UFC). In the hospital there was a regular alternation between 'good' and 'bad' days. Without exception the switch from normal to depressive mood occurred between 22:00 and 2:30, when the patient was sleeping. The switch from depressive to good mood was variable and occurred in the late morning or in the afternoon. On a 24-hour basis a highly significant correlation was seen between the mood state and the UFC excretion: r = 0.73, P less than 0.001 (hospital); r = 0.82, P less than 0.01 (isolation unit). The shape of the 24-hour profile for the UFC excretion was similar on good and bad days, with a maximum between 2:30 and 7:00 and a minimum between 19:00 and 2:30. However, on bad days UFC was elevated at all clock times. A decrease in adrenal cortical activity preceded or was parallel to substantial improvement in the mood state. Internal desynchronization occurred in the isolation unit but not in the hospital, with a rest-activity period of 18.6 h and a period close to 24 h for UFC excretion. Changes in mood were associated with both cycles, and a very close link between the switch from normal to depressive mood and the sleep state could be demonstrated."} {"id": "PMID:162501", "title": "Further validation of a questionnaire method for classifying depressive illness.", "content": "A total of 367 patients admitted to a psychiatric facility completed the LPD questionnaire. By application a decision rule to their responses, they were classified as 'non-endogenous depression', 'endogenous depression' and 'non-depressive syndrome'. This classification was found to be associated significantly with their categorization on the basis of clinical diagnosis. The findings suggest that this method of classification on the basis of responses to the LPD may have a useful research and clinical role.", "contents": "Further validation of a questionnaire method for classifying depressive illness. A total of 367 patients admitted to a psychiatric facility completed the LPD questionnaire. By application a decision rule to their responses, they were classified as 'non-endogenous depression', 'endogenous depression' and 'non-depressive syndrome'. This classification was found to be associated significantly with their categorization on the basis of clinical diagnosis. The findings suggest that this method of classification on the basis of responses to the LPD may have a useful research and clinical role."} {"id": "PMID:162502", "title": "Factor patterns in depression. A replication study.", "content": "A principal component analysis was carried out on symptom ratings and selected history items from 79 depressed patients. Three interpretable factors were obtained. The first was a general factor reflecting severity. The second a bipolar factor contrasting endogenous and neurotic depression, the third a bipolar contrasting anxiety and depressive symptoms. These replicate similar factors found previously in a different sample. The stability and predictive value are emphasized of other factors as well as the endogenous-neurotic dimension.", "contents": "Factor patterns in depression. A replication study. A principal component analysis was carried out on symptom ratings and selected history items from 79 depressed patients. Three interpretable factors were obtained. The first was a general factor reflecting severity. The second a bipolar factor contrasting endogenous and neurotic depression, the third a bipolar contrasting anxiety and depressive symptoms. These replicate similar factors found previously in a different sample. The stability and predictive value are emphasized of other factors as well as the endogenous-neurotic dimension."} {"id": "PMID:162503", "title": "Psychotic and neurotic depression. Part 3. Aetiological and background factors.", "content": "Patients receiving diagnoses of 'psychotic' and 'neurotic' depression do not differ significantly in their pre-morbid experience of life events and difficulties of aetiological significance. Some aetiological differences emerge when the two groups are subdivided into their more and less extreme halves along a distribution of discriminant function scores, but these differences are not substantial. Reallocation of the extreme 20% of each diagnostic group (who are likely misclassifications) into the other group tends to enlarge these 'aetiological' differences but they are still slight. Comparison of 'endogenous' patients (those without severe life events or major difficulties) with 'reactive' patients reveals a slight tendency for the 'endogenous' group to have a higher frequency of psychotic-type symptoms. Apart from age and experience of 'past loss', no further significant differences were found in the background characteristics of depressed patients diagnosed as 'psychotic' and those diagnosed 'neurotic'.", "contents": "Psychotic and neurotic depression. Part 3. Aetiological and background factors. Patients receiving diagnoses of 'psychotic' and 'neurotic' depression do not differ significantly in their pre-morbid experience of life events and difficulties of aetiological significance. Some aetiological differences emerge when the two groups are subdivided into their more and less extreme halves along a distribution of discriminant function scores, but these differences are not substantial. Reallocation of the extreme 20% of each diagnostic group (who are likely misclassifications) into the other group tends to enlarge these 'aetiological' differences but they are still slight. Comparison of 'endogenous' patients (those without severe life events or major difficulties) with 'reactive' patients reveals a slight tendency for the 'endogenous' group to have a higher frequency of psychotic-type symptoms. Apart from age and experience of 'past loss', no further significant differences were found in the background characteristics of depressed patients diagnosed as 'psychotic' and those diagnosed 'neurotic'."} {"id": "PMID:162504", "title": "The diagnosis of depression in children.", "content": "Operational criteria for depression in children were derived from diagnostic criteria designed for adults. These criteria were applied to a series of outpatients and inpatients on a Child Psychiatry Service. Thirteen per cent of girls and 5% of boys admitted to the clinic met the criteria for depression. (For this calculation autistic, brain-damaged and seriously retarded were excluded from the clinic population.) The frequencies of criterion symptoms and some related symptoms are reported. Generally the data suggest that the significant depression does occur as an independent syndrome in children, it is relatively common in a clinic population and it does not differ obviously from depression in adults.", "contents": "The diagnosis of depression in children. Operational criteria for depression in children were derived from diagnostic criteria designed for adults. These criteria were applied to a series of outpatients and inpatients on a Child Psychiatry Service. Thirteen per cent of girls and 5% of boys admitted to the clinic met the criteria for depression. (For this calculation autistic, brain-damaged and seriously retarded were excluded from the clinic population.) The frequencies of criterion symptoms and some related symptoms are reported. Generally the data suggest that the significant depression does occur as an independent syndrome in children, it is relatively common in a clinic population and it does not differ obviously from depression in adults."} {"id": "PMID:162506", "title": "An analysis of lumbar intervertebral disc prolapse.", "content": "Clinical findings and operative results of 212 operated cases of disc protrusion are analyzed in this paper. The maximum age incidence is between 21 and 40 years. In our series disc prolapse was most common between the L4-L5 disc space, mostly on the left side, whereas the L5-S1 is more common in white people. Anthropologic differences may account for the discrepancy. A careful search should be made for disc protrusion by flexing the spine and also exploring the intervertebral foramen during surgery.", "contents": "An analysis of lumbar intervertebral disc prolapse. Clinical findings and operative results of 212 operated cases of disc protrusion are analyzed in this paper. The maximum age incidence is between 21 and 40 years. In our series disc prolapse was most common between the L4-L5 disc space, mostly on the left side, whereas the L5-S1 is more common in white people. Anthropologic differences may account for the discrepancy. A careful search should be made for disc protrusion by flexing the spine and also exploring the intervertebral foramen during surgery."} {"id": "PMID:162509", "title": "General effects of beryllium sulfate on isolated rat heart muscle mitochondrial fraction.", "content": "The effects caused by Be2+ on the properties of isolated rat heart muscle mitochondria were investigated. It has been shown that Be2+ enhances oxygen uptake by the mitochondrial fraction in the presence of oxidizable substrates. This is due to the uncoupling effect caused by Be2+ on the mitochondria, which also undergoes a swelling effect by this divalent ion that can be accounted by the retention of Be2+ by the mitochondria. The saturation of the organellae binding sites occurs when the concentration of the ion reaches a maximum of 6.2 mumoles/mg protein.", "contents": "General effects of beryllium sulfate on isolated rat heart muscle mitochondrial fraction. The effects caused by Be2+ on the properties of isolated rat heart muscle mitochondria were investigated. It has been shown that Be2+ enhances oxygen uptake by the mitochondrial fraction in the presence of oxidizable substrates. This is due to the uncoupling effect caused by Be2+ on the mitochondria, which also undergoes a swelling effect by this divalent ion that can be accounted by the retention of Be2+ by the mitochondria. The saturation of the organellae binding sites occurs when the concentration of the ion reaches a maximum of 6.2 mumoles/mg protein."} {"id": "PMID:162507", "title": "Anomaly of the gallbladder lying extraperitoneally in the internal oblique muscle: report of an unusual case.", "content": "A gallbladder occupying internal oblique muscle rather low down in the right lower abdomen, is reported. The preoperative diagnosis was an abdominal wall tumor. The operation showed that we were dealing with a gallbladder which contained stones, and which had a relatively long cystic duct. The gallbladder was very loosely attached to the liver-bed with a long mesentery. Such a variation in the gallbladder position has only once been described in the previous literature.", "contents": "Anomaly of the gallbladder lying extraperitoneally in the internal oblique muscle: report of an unusual case. A gallbladder occupying internal oblique muscle rather low down in the right lower abdomen, is reported. The preoperative diagnosis was an abdominal wall tumor. The operation showed that we were dealing with a gallbladder which contained stones, and which had a relatively long cystic duct. The gallbladder was very loosely attached to the liver-bed with a long mesentery. Such a variation in the gallbladder position has only once been described in the previous literature."} {"id": "PMID:162508", "title": "Radiation therapy of the oral cavity: sequelae and management, part 2.", "content": "This is the concluding portion of a two-part series dealing with the effects and manifestations in the oral cavity of radiation therapy of head and neck tumors. Preradiation and postradiation extractions in dentulous patients, as well as dental maintenance of such patients (including fluoride treatments follow-up, and restorative care), are discussed. Guidelines for the dental management of edentulous patients are also presented at length (this section covers risk of bone necrosis, soft liners, timing of denture placement, dentures and preexisting bone necrosis, soft-tissue necrosis and dentures, morbidity, and prosthodontic procedures). The article concludes with a brief discussion of osteoradionecrosis and soft-tissue necrosis.", "contents": "Radiation therapy of the oral cavity: sequelae and management, part 2. This is the concluding portion of a two-part series dealing with the effects and manifestations in the oral cavity of radiation therapy of head and neck tumors. Preradiation and postradiation extractions in dentulous patients, as well as dental maintenance of such patients (including fluoride treatments follow-up, and restorative care), are discussed. Guidelines for the dental management of edentulous patients are also presented at length (this section covers risk of bone necrosis, soft liners, timing of denture placement, dentures and preexisting bone necrosis, soft-tissue necrosis and dentures, morbidity, and prosthodontic procedures). The article concludes with a brief discussion of osteoradionecrosis and soft-tissue necrosis."} {"id": "PMID:162514", "title": "11 beta-Hydroxydehydroepiandrosterone in a case of virilizing adrenal adenoma: isolation from urine and mitochondrial conversion from dehydroepiandrosterone.", "content": "11 beta-Hydroxydehydroepiandrosterone has been isolated from the urine of a 14-yr-old girl with a virilizing adrenal adenoma. Its excretion was estimated to be 0.4 mg/24 h by gas chromatography and the compound was further identified by mass spectrometry. When [7-3H]dehydroepiandrosterone was incubated with mitochondria prepared from the adenoma, approximately 10% was converted to 11 beta-hydroxydehydroepiandrosterone. The identity of the radioactive 11 beta-hydroxydehydroepiandrosterone was verified by reversed isotopic dilution, its conversion to 11 beta-hydroxyandrostenedione, and its mobility in several chromatographic systems. This is the first demonstration of an 11 beta-hydroxylase from a human source having an affinity for dehydroepiandrosterone.", "contents": "11 beta-Hydroxydehydroepiandrosterone in a case of virilizing adrenal adenoma: isolation from urine and mitochondrial conversion from dehydroepiandrosterone. 11 beta-Hydroxydehydroepiandrosterone has been isolated from the urine of a 14-yr-old girl with a virilizing adrenal adenoma. Its excretion was estimated to be 0.4 mg/24 h by gas chromatography and the compound was further identified by mass spectrometry. When [7-3H]dehydroepiandrosterone was incubated with mitochondria prepared from the adenoma, approximately 10% was converted to 11 beta-hydroxydehydroepiandrosterone. The identity of the radioactive 11 beta-hydroxydehydroepiandrosterone was verified by reversed isotopic dilution, its conversion to 11 beta-hydroxyandrostenedione, and its mobility in several chromatographic systems. This is the first demonstration of an 11 beta-hydroxylase from a human source having an affinity for dehydroepiandrosterone."} {"id": "PMID:162511", "title": "Biological characters and bacteriophage typing of Staphylococcus aureus isolated from chicken staphylococcosis and commercial balanced chicken food in Argentine.", "content": "During 1976-78, 33 S. aureus strains were isolated from chickens suffering from dermatitis and septicemia, omphalitis, pneumonia, arthritis and tenosynovitis; and from a commercial balanced chicken food. All the strains were classified into the biotype B of H\u00e1jek and Mars\u00e1lek. Twenty-nine (87.8%) strains could be classified into Sato et al biological type 4 although they differed from it in its ability to grow at 45 degrees C. The remaining 4 strains differed from the others because they failed in producing hemolysis in bovine and ovine blood agar, egg yolk reaction and splitting of Tween 80. Thirty (90.9%) strains were lysed by avian phages: 28 strains at 1 x RTD and 2 at 100 x RTD. Twenty seven (93.1% strains of the Sato et al biotype 4 were sensitive to the phages CH42/CH43/CH63/CH37 of avian group II, and 2 strains to the phage CHA1 at 100 x RTD. Only one of the 4 unclassified strains could be typed by phage CH4 of avian group I at 1 x RTD. Twenty seven (81,8%) strains were typable at 100 x RTD by the basic set of human phages: 26 strains belonged to group III (53 and 53/77) and 1 to a mixed group I/III (79/53/77). The typable strains belonged only to Sato et al biotype 4. None of 33 strains were sensitive to any of the bovine phages. The biological characters and bacteriophage typing of the S. aureus showed that almost all the strains belong to chicken types. The strains isolated from food belong to the same chicken biotype and phagetype as the strains isolated from dermatitis, septicemia, omphalitis and pneumonia. The strains isolated from arthritis and tenosynovitis were different from the ones isolated from other pathologies.", "contents": "Biological characters and bacteriophage typing of Staphylococcus aureus isolated from chicken staphylococcosis and commercial balanced chicken food in Argentine. During 1976-78, 33 S. aureus strains were isolated from chickens suffering from dermatitis and septicemia, omphalitis, pneumonia, arthritis and tenosynovitis; and from a commercial balanced chicken food. All the strains were classified into the biotype B of H\u00e1jek and Mars\u00e1lek. Twenty-nine (87.8%) strains could be classified into Sato et al biological type 4 although they differed from it in its ability to grow at 45 degrees C. The remaining 4 strains differed from the others because they failed in producing hemolysis in bovine and ovine blood agar, egg yolk reaction and splitting of Tween 80. Thirty (90.9%) strains were lysed by avian phages: 28 strains at 1 x RTD and 2 at 100 x RTD. Twenty seven (93.1% strains of the Sato et al biotype 4 were sensitive to the phages CH42/CH43/CH63/CH37 of avian group II, and 2 strains to the phage CHA1 at 100 x RTD. Only one of the 4 unclassified strains could be typed by phage CH4 of avian group I at 1 x RTD. Twenty seven (81,8%) strains were typable at 100 x RTD by the basic set of human phages: 26 strains belonged to group III (53 and 53/77) and 1 to a mixed group I/III (79/53/77). The typable strains belonged only to Sato et al biotype 4. None of 33 strains were sensitive to any of the bovine phages. The biological characters and bacteriophage typing of the S. aureus showed that almost all the strains belong to chicken types. The strains isolated from food belong to the same chicken biotype and phagetype as the strains isolated from dermatitis, septicemia, omphalitis and pneumonia. The strains isolated from arthritis and tenosynovitis were different from the ones isolated from other pathologies."} {"id": "PMID:162515", "title": "Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production.", "content": "Plasma levels of dehydroepiandrosterone sulfate (DHAS) were measured in 513 normal full term newborns, infants, children, adolescents, and adults and the results were expressed in micrograms per dl. In infancy and childhood, DHAS levels were similar in both sexes. In 74 neonates, mixed cord blood mean values /+- SD were 134.6 +/- 64. During the first day of life, plasma DHAS levels were 140 +/- 125 in 33 neonates. During the first month of life, DHAS decreased drastically, then more progressively until the 6th month of life. Between 1-6 months of age, mean levels were 5.9 +/- 4.7 in 40 children. DHAS was very low between 1-6 yr of life (2.3 +/- 1.6) and rose abruptly at the 7th year of life. Thereafter, DHAS continued to increase correlatively with age and pubertal stages in both sexes, a further increase after age 16 or pubertal stage P5 was noted only in male subjects. In adults, DHAS was significantly higher in male (224 +/- 93) than in female (138.3 +/- 51) subjects. DHAS levels were compared to those of dehydroepiandrosterone; at two periods of life, early infancy and adulthood, their patterns differed. After long term hCG stimulation, DHAS increased significantly in 45 normal prepubertal boys and in 2 boys with adrenal insufficiency. These data would suggest a direct testicular production of DHAS.", "contents": "Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production. Plasma levels of dehydroepiandrosterone sulfate (DHAS) were measured in 513 normal full term newborns, infants, children, adolescents, and adults and the results were expressed in micrograms per dl. In infancy and childhood, DHAS levels were similar in both sexes. In 74 neonates, mixed cord blood mean values /+- SD were 134.6 +/- 64. During the first day of life, plasma DHAS levels were 140 +/- 125 in 33 neonates. During the first month of life, DHAS decreased drastically, then more progressively until the 6th month of life. Between 1-6 months of age, mean levels were 5.9 +/- 4.7 in 40 children. DHAS was very low between 1-6 yr of life (2.3 +/- 1.6) and rose abruptly at the 7th year of life. Thereafter, DHAS continued to increase correlatively with age and pubertal stages in both sexes, a further increase after age 16 or pubertal stage P5 was noted only in male subjects. In adults, DHAS was significantly higher in male (224 +/- 93) than in female (138.3 +/- 51) subjects. DHAS levels were compared to those of dehydroepiandrosterone; at two periods of life, early infancy and adulthood, their patterns differed. After long term hCG stimulation, DHAS increased significantly in 45 normal prepubertal boys and in 2 boys with adrenal insufficiency. These data would suggest a direct testicular production of DHAS."} {"id": "PMID:162516", "title": "Decline of adrenal androgen production as measured by radioimmunoassay of urinary unconjugated dehyroepiandrosterone.", "content": "Dehydroepiandrosterone (DHA), in large part a measure of adrenal androgen secretion, previously has been measured in urine after hydrolysis or solvolysis of the glucuronide and sulfate conjugates. These procedures are time consuming; they often require several days and variable recoveries are a source of error. A method is presented here for determination of unconjugated DHA in 24-h urine specimens which requires less time, labor, and sample volume than necessary for the assay of DHA derived from conjugates. In 76 men and women, age 20-96 yr, total 24-h urinary unconjugated DHA showed no sex differences. However, the mean unconjugated DHA excretion decreased, which may indicate decreased zona reticularis function with respect to relatively constant zona fasiculata function in advancing age.", "contents": "Decline of adrenal androgen production as measured by radioimmunoassay of urinary unconjugated dehyroepiandrosterone. Dehydroepiandrosterone (DHA), in large part a measure of adrenal androgen secretion, previously has been measured in urine after hydrolysis or solvolysis of the glucuronide and sulfate conjugates. These procedures are time consuming; they often require several days and variable recoveries are a source of error. A method is presented here for determination of unconjugated DHA in 24-h urine specimens which requires less time, labor, and sample volume than necessary for the assay of DHA derived from conjugates. In 76 men and women, age 20-96 yr, total 24-h urinary unconjugated DHA showed no sex differences. However, the mean unconjugated DHA excretion decreased, which may indicate decreased zona reticularis function with respect to relatively constant zona fasiculata function in advancing age."} {"id": "PMID:162517", "title": "Adrenal suppression with aminoglutethimide. III. Comparison of plasma delta 4- and delta 5-steroids in postmenopausal women treated for breast carcinoma.", "content": "A regimen or aminoglutethimide in combination with replacement glucocorticoid has been used to suppress adrenal steroidogenesis in postmenopausal women with metastatic breast carcinoma. During acute and chronic treatment with aminoglutethimide, the levels of the delta 4-steroids [progesterone (P), 17 alpha-hydroxyprogesterone (17-delta 4-P), and androstenedione (delta 4-A)] and the delta 5-steroids [dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and 17 alpha-hydroxypregnenolone (17-delta 5-P)] were determine. In the total group of women, the plasma levels of P and delta 4-A increased 2- to 3-fold (P less than 0.05) while 17-delta 4-P rose 10-fold (P less than 0.01) from basal concentrations of 0.65 +/- 0.07 to 6.48 +/- 1.46 ng/ml during the initial 2 weeks of therapy with aminoglutethimide (AG) and dexamethasone. These three steroids then fell to basal levels during chronic treatment (P and 17-delta 4-P) or were suppressed (delta 4-A; P less than 0.001). In contrast, the levels of delta 5-steroids (17-delta 5-P, DHEA, and DHEA-S) were reduced 3- to 5-fold during the initial 2 weeks of therapy and remained suppressed throughout. The relative levels of certain delta 5- and delta 4-steroids pairs were then examined. The ratio of 17-delta 5-P to 17-delta 4-P decreased from baseline values of 2.15 +/- 0.35 to 0.38 +/- 0.21 ng/ml (P less .02) with the initiation of therapy and remained low thereafter. A similar pattern for the ratios between DHEA and delta 4-A, and DHEA-S and delta 4-A was observed. This may indicate that the regimen of AG treatment utilized may facilitate the activity of the 3 beta-ol-dehydrogenase, delta 5- to delta 4-isomerase, and accelerate the conversion of delta 5- to delta 4-steroids. The patterns of suppression of the plasma delta 4- and delta 5-steroids in oophorectomized and spontaneously postmenopausal patients with intact ovaries were analyzed separately. The plasma levels of progesterone were higher during the first 2 weeks of therapy in surgically castrate women than in spontaneously postmenopausal women (0.72 +/- 0.25 vs. 0.47 +/- 0.20 ng/ml). A similar pattern was observed for 17-delta 4-P, DHEA, and DHEA-S indicating that the adrenals might contribute to this increase. In contrast, during chronic treatment the levels of all steroids were lower in surgically castrate women than in those with intact ovaries. This suggested residual ovarian steroid during AG administration.", "contents": "Adrenal suppression with aminoglutethimide. III. Comparison of plasma delta 4- and delta 5-steroids in postmenopausal women treated for breast carcinoma. A regimen or aminoglutethimide in combination with replacement glucocorticoid has been used to suppress adrenal steroidogenesis in postmenopausal women with metastatic breast carcinoma. During acute and chronic treatment with aminoglutethimide, the levels of the delta 4-steroids [progesterone (P), 17 alpha-hydroxyprogesterone (17-delta 4-P), and androstenedione (delta 4-A)] and the delta 5-steroids [dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and 17 alpha-hydroxypregnenolone (17-delta 5-P)] were determine. In the total group of women, the plasma levels of P and delta 4-A increased 2- to 3-fold (P less than 0.05) while 17-delta 4-P rose 10-fold (P less than 0.01) from basal concentrations of 0.65 +/- 0.07 to 6.48 +/- 1.46 ng/ml during the initial 2 weeks of therapy with aminoglutethimide (AG) and dexamethasone. These three steroids then fell to basal levels during chronic treatment (P and 17-delta 4-P) or were suppressed (delta 4-A; P less than 0.001). In contrast, the levels of delta 5-steroids (17-delta 5-P, DHEA, and DHEA-S) were reduced 3- to 5-fold during the initial 2 weeks of therapy and remained suppressed throughout. The relative levels of certain delta 5- and delta 4-steroids pairs were then examined. The ratio of 17-delta 5-P to 17-delta 4-P decreased from baseline values of 2.15 +/- 0.35 to 0.38 +/- 0.21 ng/ml (P less .02) with the initiation of therapy and remained low thereafter. A similar pattern for the ratios between DHEA and delta 4-A, and DHEA-S and delta 4-A was observed. This may indicate that the regimen of AG treatment utilized may facilitate the activity of the 3 beta-ol-dehydrogenase, delta 5- to delta 4-isomerase, and accelerate the conversion of delta 5- to delta 4-steroids. The patterns of suppression of the plasma delta 4- and delta 5-steroids in oophorectomized and spontaneously postmenopausal patients with intact ovaries were analyzed separately. The plasma levels of progesterone were higher during the first 2 weeks of therapy in surgically castrate women than in spontaneously postmenopausal women (0.72 +/- 0.25 vs. 0.47 +/- 0.20 ng/ml). A similar pattern was observed for 17-delta 4-P, DHEA, and DHEA-S indicating that the adrenals might contribute to this increase. In contrast, during chronic treatment the levels of all steroids were lower in surgically castrate women than in those with intact ovaries. This suggested residual ovarian steroid during AG administration."} {"id": "PMID:162518", "title": "Dehydroepiandrosterone: kinetics of metabolism in normal men and women.", "content": "The single injection and constant infusion techniques were utilized to study the kinetics of dehydroepiandrosterone (DHEA) metabolism and its peripheral conversion to several other C19-steroids including C19-steroid sulfates. The MCRs (mean +/- SEM) for normal men and normal women were 1866 +/- 144 and 1901 +/- 87 liters/24 h, respectively. The single injection technique yielded values for rate constants (units) and volumes of distribution (1) as follows: K1, 42.6 +/- 7.7 for men and 37.1 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; V1, 38.5 +/- 6.0 for men and 33.7 +/- 2.5 for women; V2, 30.4 +/- 7.3 for men and 27.5 +/- 9.9 for women. The constant infusion technique yielded values for the conversion ratios for the transformation of DHEA to several products: delta 5-androstene-3 beta, 17 beta-diol to DHEA of 0.10 +/- 0.01 for men and 0.16 +/- 0.03 for women, delta 4-androstenedione to DHEA of 0.04 +/- 0.01 for men and 0.07 +/- 0.02 for women, DHEA sulfate (DHEAS) to DHEA of 6.36 +/- 0.81 for men and 10.09 +/- 0.87 for women, delta 5-androstene-3 beta, 17 beta-diol sulfate to DHEA of 0.42 +/- 0.06 for men and 0.50 +/- 0.04 for women, and androsterone sulfate to DHEA of 1.11 +/- 0.13 for men and 2.06 +/- 0.18 for women. The ratios for the conversion to DHEA sulfate and androsterone sulfate were significantly higher for women than men. The plasma concentrations of DHEA were 8.50 +/- 0.95 and 8.75 +/- 1.01 ng/ml for men and women, respectively. The calculated production rates for DHEA were 16.34 +/- 2.66 and 16.19 +/- 1.78 mg/24 h for men and women, respectively. There was no sex difference in the binding of DHEA to plasma proteins and this is reflected in the lack of sex difference in the MCRs. Calculations indicate that DHEA is a major precursor of circulating delta 5-diol.", "contents": "Dehydroepiandrosterone: kinetics of metabolism in normal men and women. The single injection and constant infusion techniques were utilized to study the kinetics of dehydroepiandrosterone (DHEA) metabolism and its peripheral conversion to several other C19-steroids including C19-steroid sulfates. The MCRs (mean +/- SEM) for normal men and normal women were 1866 +/- 144 and 1901 +/- 87 liters/24 h, respectively. The single injection technique yielded values for rate constants (units) and volumes of distribution (1) as follows: K1, 42.6 +/- 7.7 for men and 37.1 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; V1, 38.5 +/- 6.0 for men and 33.7 +/- 2.5 for women; V2, 30.4 +/- 7.3 for men and 27.5 +/- 9.9 for women. The constant infusion technique yielded values for the conversion ratios for the transformation of DHEA to several products: delta 5-androstene-3 beta, 17 beta-diol to DHEA of 0.10 +/- 0.01 for men and 0.16 +/- 0.03 for women, delta 4-androstenedione to DHEA of 0.04 +/- 0.01 for men and 0.07 +/- 0.02 for women, DHEA sulfate (DHEAS) to DHEA of 6.36 +/- 0.81 for men and 10.09 +/- 0.87 for women, delta 5-androstene-3 beta, 17 beta-diol sulfate to DHEA of 0.42 +/- 0.06 for men and 0.50 +/- 0.04 for women, and androsterone sulfate to DHEA of 1.11 +/- 0.13 for men and 2.06 +/- 0.18 for women. The ratios for the conversion to DHEA sulfate and androsterone sulfate were significantly higher for women than men. The plasma concentrations of DHEA were 8.50 +/- 0.95 and 8.75 +/- 1.01 ng/ml for men and women, respectively. The calculated production rates for DHEA were 16.34 +/- 2.66 and 16.19 +/- 1.78 mg/24 h for men and women, respectively. There was no sex difference in the binding of DHEA to plasma proteins and this is reflected in the lack of sex difference in the MCRs. Calculations indicate that DHEA is a major precursor of circulating delta 5-diol."} {"id": "PMID:162519", "title": "Plasma levels of gonadotropins, prolactin, thyroxine, and adrenal and gonadal steroids in obese prepubertal girls.", "content": "Plasma levels of gonadotropins, PRL, T4, and adrenal and gonadal steroids were measured in two groups of 7- to 9-yr-old and 10- to 11-yr-old obese prepubertal girls, and were compared to those found in groups of nonobese girls of the same age. The data found in normal weight subjects confirm the data reported in the literature, showing a significant rise between the 7- to 9- and 10- to 11-yr groups, of FSH, pregnenolone, dehydroepiandrosterone, testosterone, and estradiol plasma levels, while LH, PRL, T4, cortisol, progesterone, 17-hydroxyprogesterone (17P), and androstenedione remained constant. In the obese subjects, pregnenolone and dehydroepiandrosterone levels are notably higher than in the normal girls, in the same range as those found in adult women; furthermore, they show no rise between the two age groups. The obese prepubertal groups had significantly higher progesterone, androstenedione, and PRL levels in comparison with those observed in girls of normal weight, but 17-hydroxyprogesterone, cortisol, testosterone, LH, and T4 were similar in both groups. Estradiol levels were markedly depressed in the obese girls; FSH levels were higher in the younger girls than in normal subjects. These data indicate that in prepubertal obesity, maturation of adrenal gland function (chiefly the delta 5 pathway), is notably enhanced, whereas gonadal secretion of estradiol is impaired in the presence of high levels of FSH and PRL.", "contents": "Plasma levels of gonadotropins, prolactin, thyroxine, and adrenal and gonadal steroids in obese prepubertal girls. Plasma levels of gonadotropins, PRL, T4, and adrenal and gonadal steroids were measured in two groups of 7- to 9-yr-old and 10- to 11-yr-old obese prepubertal girls, and were compared to those found in groups of nonobese girls of the same age. The data found in normal weight subjects confirm the data reported in the literature, showing a significant rise between the 7- to 9- and 10- to 11-yr groups, of FSH, pregnenolone, dehydroepiandrosterone, testosterone, and estradiol plasma levels, while LH, PRL, T4, cortisol, progesterone, 17-hydroxyprogesterone (17P), and androstenedione remained constant. In the obese subjects, pregnenolone and dehydroepiandrosterone levels are notably higher than in the normal girls, in the same range as those found in adult women; furthermore, they show no rise between the two age groups. The obese prepubertal groups had significantly higher progesterone, androstenedione, and PRL levels in comparison with those observed in girls of normal weight, but 17-hydroxyprogesterone, cortisol, testosterone, LH, and T4 were similar in both groups. Estradiol levels were markedly depressed in the obese girls; FSH levels were higher in the younger girls than in normal subjects. These data indicate that in prepubertal obesity, maturation of adrenal gland function (chiefly the delta 5 pathway), is notably enhanced, whereas gonadal secretion of estradiol is impaired in the presence of high levels of FSH and PRL."} {"id": "PMID:162520", "title": "Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist.", "content": "The alteration in circulating levels of PRL, GH, TSH, and cortisol was studied after the oral administration of muscimol (3-hydroxy-5-aminomethylisoxazole) to human subjects with Huntington's disease (n = 4) and chronic schizophrenia (n = 5). PRL levels rose significantly in a dose-dependent fashion within a 120-min time interval. GH rose significantly but modestly over the same time interval, whereas TSH and cortisol levels remained unchanged. Since muscimol is thought to be a potent and specific gamma-aminobutyric acid agonist, these data indicate that gamma-aminobutyric acid-mediated neural transmission may function to stimulate the release of plasma PRL and GH in human subjects.", "contents": "Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist. The alteration in circulating levels of PRL, GH, TSH, and cortisol was studied after the oral administration of muscimol (3-hydroxy-5-aminomethylisoxazole) to human subjects with Huntington's disease (n = 4) and chronic schizophrenia (n = 5). PRL levels rose significantly in a dose-dependent fashion within a 120-min time interval. GH rose significantly but modestly over the same time interval, whereas TSH and cortisol levels remained unchanged. Since muscimol is thought to be a potent and specific gamma-aminobutyric acid agonist, these data indicate that gamma-aminobutyric acid-mediated neural transmission may function to stimulate the release of plasma PRL and GH in human subjects."} {"id": "PMID:162521", "title": "Studies on human sexual development. VI. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol in amniotic fluid throughout gestation.", "content": "Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol were measured in samples of amniotic fluid from uneventful pregnancies of 9-40 weeks conceptual age. There was no apparent influence of fetal sex upon the levels of these steroids. Dehydroepiandrosterone concentrations rose slightly from 9-20 weeks, and then showed little further change. Estradiol concentrations declined slightly from 9-20 weeks; after 32 weeks gestation, there was a 2-fold rise to term. Estriol levels rose in almost exponential fashion throughout gestation.", "contents": "Studies on human sexual development. VI. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol in amniotic fluid throughout gestation. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol were measured in samples of amniotic fluid from uneventful pregnancies of 9-40 weeks conceptual age. There was no apparent influence of fetal sex upon the levels of these steroids. Dehydroepiandrosterone concentrations rose slightly from 9-20 weeks, and then showed little further change. Estradiol concentrations declined slightly from 9-20 weeks; after 32 weeks gestation, there was a 2-fold rise to term. Estriol levels rose in almost exponential fashion throughout gestation."} {"id": "PMID:162522", "title": "The ventricular A wave: a new echocardiographic index of late diastolic filling of the left ventricle.", "content": "Echocardiography was used to evaluate the late diastolic filling period of the left ventricle in 30 normal individuals, 25 patients with left ventricular hypertrophy, normal sinus rhythm, and either a normal or delayed mitral valve closure, and 15 patients with atrial fibrillation. The echocardiographic ventricular A wave (VAW) was defined as the difference between the end-diastolic and an earlier late-diastolic internal left ventricular dimension, and it was felt to primarily reflect the atrial contribution to late diastolic filling of the left ventricle. It disappeared during ventricular pacing and was significantly smaller than normal in patients with atrial fibrillation. The VAW was significantly larger in patients with left ventricular hypertrophy and normal mitral valve closure reflecting the greater contribution by atrial contraction to late diastolic filling in these patients. In patients with left ventricular hypertrophy and delayed mitral valve closure, the VAW was normal reflecting lesser ventricular enlargement with atrial contraction than in the other patients with left ventricular hypertrophy. This suggested a greater impairment to left ventricular filling in these patients. Therefore, the VAW appears to be an indicator of abnormalities of late diastolic filling caused by left ventricular hypertrophy.", "contents": "The ventricular A wave: a new echocardiographic index of late diastolic filling of the left ventricle. Echocardiography was used to evaluate the late diastolic filling period of the left ventricle in 30 normal individuals, 25 patients with left ventricular hypertrophy, normal sinus rhythm, and either a normal or delayed mitral valve closure, and 15 patients with atrial fibrillation. The echocardiographic ventricular A wave (VAW) was defined as the difference between the end-diastolic and an earlier late-diastolic internal left ventricular dimension, and it was felt to primarily reflect the atrial contribution to late diastolic filling of the left ventricle. It disappeared during ventricular pacing and was significantly smaller than normal in patients with atrial fibrillation. The VAW was significantly larger in patients with left ventricular hypertrophy and normal mitral valve closure reflecting the greater contribution by atrial contraction to late diastolic filling in these patients. In patients with left ventricular hypertrophy and delayed mitral valve closure, the VAW was normal reflecting lesser ventricular enlargement with atrial contraction than in the other patients with left ventricular hypertrophy. This suggested a greater impairment to left ventricular filling in these patients. Therefore, the VAW appears to be an indicator of abnormalities of late diastolic filling caused by left ventricular hypertrophy."} {"id": "PMID:162523", "title": "Left ventricular function in beta-thalassemia and the effect of multiple transfusions.", "content": "Left ventricular performance was studied in 23 young patients with severe chronic anemia due to beta-thalassemia major and intermedia. The patients were divided into three groups according to the number of blood transfusions they had received. The left ventricle (LV) was enlarged in patients who had not received blood and larger still in patients who had received multiple transfusions. Echocardiography and systolic time interval measurements showed that systolic function of the LV was good in all the patients and that there was no statistical difference in systolic function in patients who had and those who had not received multiple transfusions. Heart rate was increased in the latter group. Stroke index and cardiac index were high, especially in patients in Group 3. The diastolic closure rate (EF slope) of the anterior mitral leaflet and its amplitude of movement were increased, but less so in Group 3; this may reflect an alteration in diastolic LV distensibility. The results indicate that despite the presence of cardiomegaly and severe clinical congestive heart failure, LV performance is well preserved in patients with beta-thalassemia, even in those who have received repeated blood transfusions. Clinical cardiac failure is the consequence of volume overload and abnormal chamber compliance. There was no evidence in this of a congestive cardiomyopathy.", "contents": "Left ventricular function in beta-thalassemia and the effect of multiple transfusions. Left ventricular performance was studied in 23 young patients with severe chronic anemia due to beta-thalassemia major and intermedia. The patients were divided into three groups according to the number of blood transfusions they had received. The left ventricle (LV) was enlarged in patients who had not received blood and larger still in patients who had received multiple transfusions. Echocardiography and systolic time interval measurements showed that systolic function of the LV was good in all the patients and that there was no statistical difference in systolic function in patients who had and those who had not received multiple transfusions. Heart rate was increased in the latter group. Stroke index and cardiac index were high, especially in patients in Group 3. The diastolic closure rate (EF slope) of the anterior mitral leaflet and its amplitude of movement were increased, but less so in Group 3; this may reflect an alteration in diastolic LV distensibility. The results indicate that despite the presence of cardiomegaly and severe clinical congestive heart failure, LV performance is well preserved in patients with beta-thalassemia, even in those who have received repeated blood transfusions. Clinical cardiac failure is the consequence of volume overload and abnormal chamber compliance. There was no evidence in this of a congestive cardiomyopathy."} {"id": "PMID:162524", "title": "Congenital tricuspid incompetence simulating pulmonary atresia with intact ventricular septum: a report of two cases.", "content": "Two infants with isolated congenital tricuspid incompetence appeared to have associated right ventricular outflow tract obstruction at diagnostic evaluation, including catheterization and cineangiography. One infant died during surgery; the other improved rapidly and survived with medical therapy. We discuss the problem of establishing the presence of patency of the right ventricular outflow tract in infants with massive tricuspid incompetence and outline an approach to the management of infants whose diagnosis remains unclear even after careful evaluation.", "contents": "Congenital tricuspid incompetence simulating pulmonary atresia with intact ventricular septum: a report of two cases. Two infants with isolated congenital tricuspid incompetence appeared to have associated right ventricular outflow tract obstruction at diagnostic evaluation, including catheterization and cineangiography. One infant died during surgery; the other improved rapidly and survived with medical therapy. We discuss the problem of establishing the presence of patency of the right ventricular outflow tract in infants with massive tricuspid incompetence and outline an approach to the management of infants whose diagnosis remains unclear even after careful evaluation."} {"id": "PMID:162525", "title": "A genetic analysis of the Papillon-Lef\u00e8vre syndrome in a Jewish family from Cochin.", "content": "The Papillon-Lef\u00e8vre syndrome (PLS) is segregating in a large kindred of a Jewish isolate originating from Cochin, India. The frequency of the gene responsible for PLS among the Cochin Jews, 0.1, was estimated from the number of unrelated carriers in the isolate who married into the kindred. The obvious discrepancy between this apparently high gene frequency and the total absence of PLS in other kindreds of the isolate suggests that the syndrome may not behave as a simple autosomal recessive trait.", "contents": "A genetic analysis of the Papillon-Lef\u00e8vre syndrome in a Jewish family from Cochin. The Papillon-Lef\u00e8vre syndrome (PLS) is segregating in a large kindred of a Jewish isolate originating from Cochin, India. The frequency of the gene responsible for PLS among the Cochin Jews, 0.1, was estimated from the number of unrelated carriers in the isolate who married into the kindred. The obvious discrepancy between this apparently high gene frequency and the total absence of PLS in other kindreds of the isolate suggests that the syndrome may not behave as a simple autosomal recessive trait."} {"id": "PMID:162526", "title": "A detailed description of mothers' knowledge before genetic counseling for Down syndrome: Part I.", "content": "This study focuses on counselees' knowledge of the Down syndrome before receiving genetic counseling. Data were collected from 47 mothers of children with the Down syndrome using a structured interview of 13 open-ended questions. This instrument was found to be both internally reliable and consistent. Results of this study document the enormous variation of counselees' knowledge of the Down syndrome before genetic counseling and show that this is positively associated with their educational background. Counselees with more than a high school education knew about 60% of the genetic information pertaining to the diagnosis before genetic counseling, while those with less than a high school education knew only 23% of this information before counseling. These results indicate that the better educated counselees are less apt to need to learn basic genetic information and may seek out genetic counseling services for other reasons. Possible motives are seeking knowledge confirmation, emotional support, and personalization of the information.", "contents": "A detailed description of mothers' knowledge before genetic counseling for Down syndrome: Part I. This study focuses on counselees' knowledge of the Down syndrome before receiving genetic counseling. Data were collected from 47 mothers of children with the Down syndrome using a structured interview of 13 open-ended questions. This instrument was found to be both internally reliable and consistent. Results of this study document the enormous variation of counselees' knowledge of the Down syndrome before genetic counseling and show that this is positively associated with their educational background. Counselees with more than a high school education knew about 60% of the genetic information pertaining to the diagnosis before genetic counseling, while those with less than a high school education knew only 23% of this information before counseling. These results indicate that the better educated counselees are less apt to need to learn basic genetic information and may seek out genetic counseling services for other reasons. Possible motives are seeking knowledge confirmation, emotional support, and personalization of the information."} {"id": "PMID:162527", "title": "Prenatal cytogenetic diagnosis: first 1,000 successful cases.", "content": "From February 1969 to August 1976, we studied 1,048 amniotic fluids. Of these, 958 (91.4%) were primarily for prenatal cytogenetic diagnosis. Cytogenetic studies were attempted in 1,021 cases; the diagnosis was successful in 1,000 of these. The failure rate of obtaining a diagnosis from the amniotic fluid cell culture of the first amniocentesis was 5% (50 cases); 29 cases had a repeat tap and successful diagnosis was achieved in all. In 21 cases, a repeat tap was refused. Thus, the overall failure rate of obtaining a final cytogenetic diagnosis was 2.06% (21/1,021). There were 32 fetal losses after amniocentesis including 16 spontaneous second trimester abortions, 7 fetal deaths in utero and 9 stillbirths. In two additional cases, fetal death had occurred before amniocentesis. This number of fetal losses does not exceed the number that would be expected in the same maternal age group without amniocentesis. In our series, the frequencies of trisomy in maternal age groups 40 years and over, 37-39 years, 35-36 years, and under 35 years were 4.5, 3.14, 0 and 0% respectively. These frequencies are comparable to those reported from other prospective prenatal studies and higher than those of retrospective live born studies. Various problems and pitfalls in prenatal cytogenetic diagnosis are discussed.", "contents": "Prenatal cytogenetic diagnosis: first 1,000 successful cases. From February 1969 to August 1976, we studied 1,048 amniotic fluids. Of these, 958 (91.4%) were primarily for prenatal cytogenetic diagnosis. Cytogenetic studies were attempted in 1,021 cases; the diagnosis was successful in 1,000 of these. The failure rate of obtaining a diagnosis from the amniotic fluid cell culture of the first amniocentesis was 5% (50 cases); 29 cases had a repeat tap and successful diagnosis was achieved in all. In 21 cases, a repeat tap was refused. Thus, the overall failure rate of obtaining a final cytogenetic diagnosis was 2.06% (21/1,021). There were 32 fetal losses after amniocentesis including 16 spontaneous second trimester abortions, 7 fetal deaths in utero and 9 stillbirths. In two additional cases, fetal death had occurred before amniocentesis. This number of fetal losses does not exceed the number that would be expected in the same maternal age group without amniocentesis. In our series, the frequencies of trisomy in maternal age groups 40 years and over, 37-39 years, 35-36 years, and under 35 years were 4.5, 3.14, 0 and 0% respectively. These frequencies are comparable to those reported from other prospective prenatal studies and higher than those of retrospective live born studies. Various problems and pitfalls in prenatal cytogenetic diagnosis are discussed."} {"id": "PMID:162529", "title": "[Incorporation of H3-uridine in vitro into normal lymphocytes and those in cases of aberration of acrocentric chromosomes].", "content": "Literature data indicate that the formation of ribosomes is a basic function of the nucleolus. The formation of the nucleolus depends upon the function of the nucleolus organizing region (NOR). It was shown that in man the NOR locus is situated in secondary constrictions and adjacent segments of the short arms of acrocentric chromosomes of the D and G group. The presence of DNA sequences coding for 18 S and 28 S RNA i.e. ribosomal RNA (r-RNA), was demonstrated in the secondary constriction of acrocentric chromosomes using the RNA-DNA hybridization in situ method. The genes coding for 5 S RNA which is also a component of ribosomes, are located on other chromosomes. Therefore ribosome production should be considered a polygenic process, the genes situated in the NOR locus playing a basic role in its initiation. In cases of acrocentric chromosome aberration NOR \"dosage\" changes; in cases of regular trisomy there are 11 NOR \"doses\" instead of the normal 10, occurring in 5 pairs of group D and G chromosomes, in cases of translocation trisomy there are 9 such \"doses\" and in cases of balanced translocation carriers there are 8 \"doses\". Hence the following question: do changes in the NOR \"dose\" cause changes in ribosome production? Eventual changes should influence the intensity and/or the time course of r-RNA synthesis in cells stimulated to growth and differentiation . An approximate index for the study of this phenomenon is the 3H-uridine incorporation in an adequate experimental system. It seems that the most convenient model to study this phenomenon is the blastic transformation of lymphocytes induced by phytohaemagglutinin. This process has already been investigated in depth and is well known, the material being easily accessible. Venous blood was taken from 10 patients with 21 regular trisomy, 2 cases of 21 translocation trisomy and from 21 carriers of balanced translocations. Lymphocytes from 12 healthy persons with a normal karyotype served as controls. Lymphocytes in plasma were separated from whole blood and a routine macroculture was set up adding phaseoline of standardized mitogenic activity in the quantity 0.02 ml/ml of medium. The cells were incubated for 3, 6, 12, 24 and 48 hours. One hour before termination of the incubation period 1 microCi/ml 3H-uridine was added to the medium.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "[Incorporation of H3-uridine in vitro into normal lymphocytes and those in cases of aberration of acrocentric chromosomes]. Literature data indicate that the formation of ribosomes is a basic function of the nucleolus. The formation of the nucleolus depends upon the function of the nucleolus organizing region (NOR). It was shown that in man the NOR locus is situated in secondary constrictions and adjacent segments of the short arms of acrocentric chromosomes of the D and G group. The presence of DNA sequences coding for 18 S and 28 S RNA i.e. ribosomal RNA (r-RNA), was demonstrated in the secondary constriction of acrocentric chromosomes using the RNA-DNA hybridization in situ method. The genes coding for 5 S RNA which is also a component of ribosomes, are located on other chromosomes. Therefore ribosome production should be considered a polygenic process, the genes situated in the NOR locus playing a basic role in its initiation. In cases of acrocentric chromosome aberration NOR \"dosage\" changes; in cases of regular trisomy there are 11 NOR \"doses\" instead of the normal 10, occurring in 5 pairs of group D and G chromosomes, in cases of translocation trisomy there are 9 such \"doses\" and in cases of balanced translocation carriers there are 8 \"doses\". Hence the following question: do changes in the NOR \"dose\" cause changes in ribosome production? Eventual changes should influence the intensity and/or the time course of r-RNA synthesis in cells stimulated to growth and differentiation . An approximate index for the study of this phenomenon is the 3H-uridine incorporation in an adequate experimental system. It seems that the most convenient model to study this phenomenon is the blastic transformation of lymphocytes induced by phytohaemagglutinin. This process has already been investigated in depth and is well known, the material being easily accessible. Venous blood was taken from 10 patients with 21 regular trisomy, 2 cases of 21 translocation trisomy and from 21 carriers of balanced translocations. Lymphocytes from 12 healthy persons with a normal karyotype served as controls. Lymphocytes in plasma were separated from whole blood and a routine macroculture was set up adding phaseoline of standardized mitogenic activity in the quantity 0.02 ml/ml of medium. The cells were incubated for 3, 6, 12, 24 and 48 hours. One hour before termination of the incubation period 1 microCi/ml 3H-uridine was added to the medium.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:162530", "title": "[Incorporation of C-14-glycine in vitro into normal human lymphocytes and those in cases of aberration of chromosome 21].", "content": "Since Caspersson 's and Brachet 's investigations it has been very well known that the nucleolus is a cellular center of protein synthesis regulation. Later it has been shown that the nucleolus is the site of ribosome production, that means that it produces one of the basic elements of the cytoplasmatic apparatus of protein synthesis. Morphologic observations demonstrated that the nucleolus in man is formed in close connection with secondary constrictions of acrocentric chromosomes of the D and G groups. These regions contain the nucleolus organizing region (locus NOR). By means of DNA-RNA hybridization in situ it has been established that the secondary constrictions of acrocentric chromosomes contain sequences coding ribosomal RNA synthesis. RNA synthetized on r-DNA matrix contained in NOR is transported to the nucleolus where ribonucleoprotein complexes are formed. Ribosome formation is the result of a complex process. Ribosomes are transported to the cytoplasm where they aggregate into polyribosomes on the rough ergastoplasmic reticulum. In this way the cytoplasmatic aparatus of protein synthesis is formed. Its activity depends on ribosome formation. In view of the above the question arises: will the presence of an additional chromosome coding r-RNA synthesis as in Down's syndrome, i.e. 21 trisomy, influence the course of protein synthesis? Blastic transformation of lymphocytes in vitro induced by phytohaemagglutinin is a convenient model for the study of protein synthesis in cells stimulated to growth and differentiation. This phenomenon has been very well investigated. It is well known that blastic transformation is accompanied by intensification of RNA synthesis, ribosome formation and intensification of protein synthesis. The existing literature data allow to choose adequate methods and time points for the examination of the course of protein synthesis in this model. Venous blood was obtained from 17 healthy humans with normal karyotype and from 15 cases of trisomy 21. After separation of plasma with lymphocytes routine cultures with addition of phaseoline were set up and were incubated 6, 12, 24, 48 and 72 hours. 14C-glycine was added one hour before the termination of the incubation period. Following this the number and differential count of lymphocytes were determined.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "[Incorporation of C-14-glycine in vitro into normal human lymphocytes and those in cases of aberration of chromosome 21]. Since Caspersson 's and Brachet 's investigations it has been very well known that the nucleolus is a cellular center of protein synthesis regulation. Later it has been shown that the nucleolus is the site of ribosome production, that means that it produces one of the basic elements of the cytoplasmatic apparatus of protein synthesis. Morphologic observations demonstrated that the nucleolus in man is formed in close connection with secondary constrictions of acrocentric chromosomes of the D and G groups. These regions contain the nucleolus organizing region (locus NOR). By means of DNA-RNA hybridization in situ it has been established that the secondary constrictions of acrocentric chromosomes contain sequences coding ribosomal RNA synthesis. RNA synthetized on r-DNA matrix contained in NOR is transported to the nucleolus where ribonucleoprotein complexes are formed. Ribosome formation is the result of a complex process. Ribosomes are transported to the cytoplasm where they aggregate into polyribosomes on the rough ergastoplasmic reticulum. In this way the cytoplasmatic aparatus of protein synthesis is formed. Its activity depends on ribosome formation. In view of the above the question arises: will the presence of an additional chromosome coding r-RNA synthesis as in Down's syndrome, i.e. 21 trisomy, influence the course of protein synthesis? Blastic transformation of lymphocytes in vitro induced by phytohaemagglutinin is a convenient model for the study of protein synthesis in cells stimulated to growth and differentiation. This phenomenon has been very well investigated. It is well known that blastic transformation is accompanied by intensification of RNA synthesis, ribosome formation and intensification of protein synthesis. The existing literature data allow to choose adequate methods and time points for the examination of the course of protein synthesis in this model. Venous blood was obtained from 17 healthy humans with normal karyotype and from 15 cases of trisomy 21. After separation of plasma with lymphocytes routine cultures with addition of phaseoline were set up and were incubated 6, 12, 24, 48 and 72 hours. 14C-glycine was added one hour before the termination of the incubation period. Following this the number and differential count of lymphocytes were determined.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:162531", "title": "[A report on studies on the child's adaptation to school and family environment after neoplastic disease].", "content": "The objective of this study was to learn the course of child's adaptation process to school and family environment following the neoplastic disease. The study also aimed select the environment and personality factors influencing adaptation effect. The study pertains to the child's personality and how it works at home and at school. It also tries to get to know the child's environment. 65 children of different social environment were studied. Motor functions of these children were limited as the result of tumour disease. Special scale of adaptation was prepared when the research was over. By means of this sale two groups of children were distinguished: those who were well adapted to the environment and those who were not. Statistical analysis was used to compare the groups on account of the following factors: health factors including: a kind of tumour, duration of the disease, prevalence of pain, manipulation and locomotive abilities, visibility of handicap; sociological factors including: age and sex of studied persons, the place of residence and education of parent's, living standard of the family, a degree of family participation in cultural life of the society, mother's attitude towards the insane child. These factors allow to formulate the following dependences: The more a level of the child's locomotive functions, following neoplastic disease approaches to the standard, the more favourable course takes the process of child's adaptation to the family and peers. If a neoplastic disease leaves permanent and always visible handicap then child's adaptation effect to the environment is not favourable. An active participation of the family in socially life is beneficial for regular adaptation of a child. Personality development as the result of participation in cultural life allows socially accepted defence mechanism to work in stress situations connected with the disease. Parent's rational attitude towards an insane child correlates with a beneficial child's adaptation to an environment. Other factors did not differentiate the two groups statistically. During clinicalontgenetic analysis concerning particular studied cases, 3 models of nonfunctional adaptation were distinguished: maladjustment of aggressive type prevailing among the children with permanent physical handicap coming of families characteristic for socially nonaccepted standard of behaviour; maladjustment of neurotic type prevailing among the children coming of compliant families whose adult members manifest neurotic vegetative reactions in difficult situations.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "[A report on studies on the child's adaptation to school and family environment after neoplastic disease]. The objective of this study was to learn the course of child's adaptation process to school and family environment following the neoplastic disease. The study also aimed select the environment and personality factors influencing adaptation effect. The study pertains to the child's personality and how it works at home and at school. It also tries to get to know the child's environment. 65 children of different social environment were studied. Motor functions of these children were limited as the result of tumour disease. Special scale of adaptation was prepared when the research was over. By means of this sale two groups of children were distinguished: those who were well adapted to the environment and those who were not. Statistical analysis was used to compare the groups on account of the following factors: health factors including: a kind of tumour, duration of the disease, prevalence of pain, manipulation and locomotive abilities, visibility of handicap; sociological factors including: age and sex of studied persons, the place of residence and education of parent's, living standard of the family, a degree of family participation in cultural life of the society, mother's attitude towards the insane child. These factors allow to formulate the following dependences: The more a level of the child's locomotive functions, following neoplastic disease approaches to the standard, the more favourable course takes the process of child's adaptation to the family and peers. If a neoplastic disease leaves permanent and always visible handicap then child's adaptation effect to the environment is not favourable. An active participation of the family in socially life is beneficial for regular adaptation of a child. Personality development as the result of participation in cultural life allows socially accepted defence mechanism to work in stress situations connected with the disease. Parent's rational attitude towards an insane child correlates with a beneficial child's adaptation to an environment. Other factors did not differentiate the two groups statistically. During clinicalontgenetic analysis concerning particular studied cases, 3 models of nonfunctional adaptation were distinguished: maladjustment of aggressive type prevailing among the children with permanent physical handicap coming of families characteristic for socially nonaccepted standard of behaviour; maladjustment of neurotic type prevailing among the children coming of compliant families whose adult members manifest neurotic vegetative reactions in difficult situations.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:162533", "title": "Maternal age and Down syndrome: age-specific incidence rates by single-year intervals.", "content": "Maternal age-specific risks of giving birth to a child with the Down syndrome (DS) are given by single-year age intervals. Such data are of value for more precise genetic counseling and in cost-benefit analyses of prenatal diagnosis programs. The data were obtained by linking records of children with DS at the British Columbia Health Surveillance Registry ( BCHSR ) to the appropriate birth registrations to derive maternal ages. The data related to 519 affected children out of a total of 354,880 live births in British Columbia between 1961 and 1970. The results, which are based on a high level of ascertainment, are compared to those reported in the only other published study relating to risks by single-year maternal age groupings, where completeness of ascertainment was estimated to be only 38%.", "contents": "Maternal age and Down syndrome: age-specific incidence rates by single-year intervals. Maternal age-specific risks of giving birth to a child with the Down syndrome (DS) are given by single-year age intervals. Such data are of value for more precise genetic counseling and in cost-benefit analyses of prenatal diagnosis programs. The data were obtained by linking records of children with DS at the British Columbia Health Surveillance Registry ( BCHSR ) to the appropriate birth registrations to derive maternal ages. The data related to 519 affected children out of a total of 354,880 live births in British Columbia between 1961 and 1970. The results, which are based on a high level of ascertainment, are compared to those reported in the only other published study relating to risks by single-year maternal age groupings, where completeness of ascertainment was estimated to be only 38%."} {"id": "PMID:162535", "title": "Influence of seminal additives and packaging systems on fertility of frozen bovine spermatozoa.", "content": "The following recommendations and conclusions are based upon results of fertility and laboratory studies, and general trends from field investigations. Fertility results due to the addition of enzymes have been variable and contradictory. Flushing of ampules with dry, gaseous nitrogen prior to filling has become a routine practice in processing semen to be frozen. For control of Vibrio fetus and Leptospira pomona, 2,000 micrograms of streptomycin and 1,000 u polymyxin B sulfate should be added per milliliter of raw semen immediately after collection. The extender for initial dilution should contain the same concentration of antibiotics used for raw semen plus 500 u penicillin. The glycerol portion of the extender should contain 500 u penicillin per milliliter. The effect of addition of sugars on fertility has been highly variable. The primary beneficial effect is probably due to their cryoprotective properties. A myriad of concoctions have been added to bovine semen and the results have been highly variable with respect to both motility and fertility. Results of subsequent experiments have rarely proven that addition of exotic compounds or mixtures has been of value. Higher mean fertility was obtained with semen in straws in 14 of 21 comparisons with ampules. The differences in favor of straws ranged from 1.1 to 18.9; while the range in favor of ampules was .1 to 4.4 percentage points. Fertility obtained with pellets has ranged from minus 12.8 to plus 11.9 percentage points in nonreturn rate (NR), compared to the corresponding NR with semen in ampules. Fertility of semen in ampules was higher in five of eight studies. Fertility of pelleted semen has ranged from minus 9.5 to plus 6.0 percentage points compared with straws. Fertility was higher for semen in pellets in only one of five investigations. Pellets should not be used until the potential for pathogenic contamination and exchange of spermatozoa among pellets is eliminated. There is a potential for higher fertility with semen in straws as compared to other packaging systems, but the issue of liquid nitrogen (LN) entry and possible contamination of semen should be further investigated. In general, fertility obtained with semen frozen in the .25 ml straw has been equal to or higher than semen in larger packages. However, they cannot be unequivocally recommended due to other considerations. From laboratory studies, it appears that greater spermatozoan survival is obtained when semen frozen in straws is thawed in water at 35 C or above.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Influence of seminal additives and packaging systems on fertility of frozen bovine spermatozoa. The following recommendations and conclusions are based upon results of fertility and laboratory studies, and general trends from field investigations. Fertility results due to the addition of enzymes have been variable and contradictory. Flushing of ampules with dry, gaseous nitrogen prior to filling has become a routine practice in processing semen to be frozen. For control of Vibrio fetus and Leptospira pomona, 2,000 micrograms of streptomycin and 1,000 u polymyxin B sulfate should be added per milliliter of raw semen immediately after collection. The extender for initial dilution should contain the same concentration of antibiotics used for raw semen plus 500 u penicillin. The glycerol portion of the extender should contain 500 u penicillin per milliliter. The effect of addition of sugars on fertility has been highly variable. The primary beneficial effect is probably due to their cryoprotective properties. A myriad of concoctions have been added to bovine semen and the results have been highly variable with respect to both motility and fertility. Results of subsequent experiments have rarely proven that addition of exotic compounds or mixtures has been of value. Higher mean fertility was obtained with semen in straws in 14 of 21 comparisons with ampules. The differences in favor of straws ranged from 1.1 to 18.9; while the range in favor of ampules was .1 to 4.4 percentage points. Fertility obtained with pellets has ranged from minus 12.8 to plus 11.9 percentage points in nonreturn rate (NR), compared to the corresponding NR with semen in ampules. Fertility of semen in ampules was higher in five of eight studies. Fertility of pelleted semen has ranged from minus 9.5 to plus 6.0 percentage points compared with straws. Fertility was higher for semen in pellets in only one of five investigations. Pellets should not be used until the potential for pathogenic contamination and exchange of spermatozoa among pellets is eliminated. There is a potential for higher fertility with semen in straws as compared to other packaging systems, but the issue of liquid nitrogen (LN) entry and possible contamination of semen should be further investigated. In general, fertility obtained with semen frozen in the .25 ml straw has been equal to or higher than semen in larger packages. However, they cannot be unequivocally recommended due to other considerations. From laboratory studies, it appears that greater spermatozoan survival is obtained when semen frozen in straws is thawed in water at 35 C or above.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:162536", "title": "Isolation and characterization of nuclei from Neurospora crassa.", "content": "A procedure was developed for isolating nuclei from either the conidial or germinated conidial growth phase of Neurospora crassa. A frozen conidial suspension was lysed by passage through a French pressure cell, and the nuclei were freed from the broken cells by repeated homogenization in an Omni-Mixer. Pure nuclei were obtained from the crude nuclear fraction by density banding in a Ludox gradient. The final nuclear yield was 20 to 30%. The nuclei had a deoxyribonucleic acid (DNA):ribonucleic acid (RNA):protein ratio of 1:3.5:7 and were active in RNA synthesis. The nuclei, stained with the DNA stain 4,6-diamidino-2-phenylindole, appeared under fluorescence microscopy as bright blue spheres, 1 micron in diameter, essentially free from cytoplasmic attachments. Chromatin extracted from the nuclei in a 70 to 75% yield by dissociation with 2 M sodium chloride and 5 M urea had a DNA:RNA:protein ratio of 1:1.05:1.7. Chromatin reconstituted from this preparation exhibited a level of RNA polymerase template activity lower than that of pure Neurospora DNA, but the maximum level of reconstitution obtained was only 10%. Fractionation of Neurospora chromatin on hydroxylapatite separated the histones from the chromatin acidic proteins. The normal complement of histone proteins was present in both the reconstituted and dissociated chromatin preparations. The acidic protein fraction exhibited a variety of bands on sodium dodecyl sulfate gel electrophoresis ranging in molecular weight from 15,000 to 70,000. The gel pattern was much more complex for total dissociated chromatin than for reconstituted chromatin.", "contents": "Isolation and characterization of nuclei from Neurospora crassa. A procedure was developed for isolating nuclei from either the conidial or germinated conidial growth phase of Neurospora crassa. A frozen conidial suspension was lysed by passage through a French pressure cell, and the nuclei were freed from the broken cells by repeated homogenization in an Omni-Mixer. Pure nuclei were obtained from the crude nuclear fraction by density banding in a Ludox gradient. The final nuclear yield was 20 to 30%. The nuclei had a deoxyribonucleic acid (DNA):ribonucleic acid (RNA):protein ratio of 1:3.5:7 and were active in RNA synthesis. The nuclei, stained with the DNA stain 4,6-diamidino-2-phenylindole, appeared under fluorescence microscopy as bright blue spheres, 1 micron in diameter, essentially free from cytoplasmic attachments. Chromatin extracted from the nuclei in a 70 to 75% yield by dissociation with 2 M sodium chloride and 5 M urea had a DNA:RNA:protein ratio of 1:1.05:1.7. Chromatin reconstituted from this preparation exhibited a level of RNA polymerase template activity lower than that of pure Neurospora DNA, but the maximum level of reconstitution obtained was only 10%. Fractionation of Neurospora chromatin on hydroxylapatite separated the histones from the chromatin acidic proteins. The normal complement of histone proteins was present in both the reconstituted and dissociated chromatin preparations. The acidic protein fraction exhibited a variety of bands on sodium dodecyl sulfate gel electrophoresis ranging in molecular weight from 15,000 to 70,000. The gel pattern was much more complex for total dissociated chromatin than for reconstituted chromatin."} {"id": "PMID:162537", "title": "Isolation and characterization of nondefective transducing lambda bacteriophages carrying fla genes of Escherichia coli K-12.", "content": "In Escherichia coli K-12, 11 fla genes and a hag gene are located between his and uvrC, making two clusters at map positions 42.5 and 43.0 min. Nondefective transducing lambda phages for these genes were isolated. Low-frequency-transducing donors were constructed starting from lysogens of lambda cI857 in which the prophage is integrated at a secondary attachment site at 44 min on the E. coli map. Two strategies were used to delete the region between the prophage and the fla genes. Deletion mutants of the supD locus between fla and the prophage were isolated by selecting for loss of Su1+, an allele of supD. A strain with a deletion starting within the prophage and ending at a position close to the fla genes was isolated from heat-resistant derivatives of the lysogen. A lysogen of lambda b2 was then constructed in which the prophage had integrated at the site of the defective prophage by means of recombination with residual lambda deoxyribonucleic acid. From low-frequency-transducing lysate of the donor strains thus constructed, either directly or in combination with a procedure that extends the loci transduced, various lambda pfla's were isolated. lambda pflaL1 carries all nine fla genes at 43 min, and lambda pflaH14 carries hag and two fla genes at 42.5 min.", "contents": "Isolation and characterization of nondefective transducing lambda bacteriophages carrying fla genes of Escherichia coli K-12. In Escherichia coli K-12, 11 fla genes and a hag gene are located between his and uvrC, making two clusters at map positions 42.5 and 43.0 min. Nondefective transducing lambda phages for these genes were isolated. Low-frequency-transducing donors were constructed starting from lysogens of lambda cI857 in which the prophage is integrated at a secondary attachment site at 44 min on the E. coli map. Two strategies were used to delete the region between the prophage and the fla genes. Deletion mutants of the supD locus between fla and the prophage were isolated by selecting for loss of Su1+, an allele of supD. A strain with a deletion starting within the prophage and ending at a position close to the fla genes was isolated from heat-resistant derivatives of the lysogen. A lysogen of lambda b2 was then constructed in which the prophage had integrated at the site of the defective prophage by means of recombination with residual lambda deoxyribonucleic acid. From low-frequency-transducing lysate of the donor strains thus constructed, either directly or in combination with a procedure that extends the loci transduced, various lambda pfla's were isolated. lambda pflaL1 carries all nine fla genes at 43 min, and lambda pflaH14 carries hag and two fla genes at 42.5 min."} {"id": "PMID:162540", "title": "Aorticopulmonary window associated with tetralogy of Fallot. Report of one case and review of the literature.", "content": "A case of aorticopulmonary window associated with tetralogy of Fallot is reported with its clinical, hemodynamic, angiocardiographic, surgical, and necropsy findings. The difficulty in diagnosing a tetralogy of Fallot in the presence of a large aorticopulmonary shunt is emphasized. It is also noted that the only means of discovering the infundibular stenosis of the right ventricle is by angiocardiographic study of the right ventricular outflow tract. The difficulty in distinguishing truncus arteriosus from an aorticopulmonary window coexisting with a ventricular septal defect is discussed, and it is pointed out that the only means of differentiating these two anomalies is the angiocardiographic finding of two sigmoid valves. An embryological hypothesis concerning the pathogenesis of this association is also discussed.", "contents": "Aorticopulmonary window associated with tetralogy of Fallot. Report of one case and review of the literature. A case of aorticopulmonary window associated with tetralogy of Fallot is reported with its clinical, hemodynamic, angiocardiographic, surgical, and necropsy findings. The difficulty in diagnosing a tetralogy of Fallot in the presence of a large aorticopulmonary shunt is emphasized. It is also noted that the only means of discovering the infundibular stenosis of the right ventricle is by angiocardiographic study of the right ventricular outflow tract. The difficulty in distinguishing truncus arteriosus from an aorticopulmonary window coexisting with a ventricular septal defect is discussed, and it is pointed out that the only means of differentiating these two anomalies is the angiocardiographic finding of two sigmoid valves. An embryological hypothesis concerning the pathogenesis of this association is also discussed."} {"id": "PMID:162541", "title": "In vitro assays of the efficacy of antimicrobial agents in controlling Chlamydia trachomatis propagation.", "content": "The antimicrobial susceptibility of a low-laboratory-passage, slow-growing, genital Chlamydia trachomatis strain was studied by five different procedures with the use of McCoy cells pretreated with 5-iodo-2-deoxyuridine. The effects of antimicrobial agents when added to cultures on day 0 or day 2 after inoculation with C. trachomatis and the effects of washing and reincubating treated cultures in antimicrobial-free media were investigated. Tetracycline and erythromycin inhibited C. trachomatis growth at concentrations attainable in human serum, although their actions were reversible and significantly higher concentrations were needed to \"cure\" 48-h infected cultures. On a weight basis, spectinomycin was relatively ineffective in inhibiting C. trachomatis growth. The minimal inhibitory concentration of penicillin measured by our assay procedures was higher than that reported by other investigators. The five assay procedures used in this study were reproducible, and our results indicate that we can obtain more pertinent information about the efficacy of an antimicrobial agent in controlling C. trachomatis growth by using a combination of these assays than by simple minimal inhibitory concentration determinations, as had been previously described by other investigators. In addition, we failed to demonstrate changes in tetracycline susceptibility of C. trachomatis isolates from two patients who had received tetracycline therapy.", "contents": "In vitro assays of the efficacy of antimicrobial agents in controlling Chlamydia trachomatis propagation. The antimicrobial susceptibility of a low-laboratory-passage, slow-growing, genital Chlamydia trachomatis strain was studied by five different procedures with the use of McCoy cells pretreated with 5-iodo-2-deoxyuridine. The effects of antimicrobial agents when added to cultures on day 0 or day 2 after inoculation with C. trachomatis and the effects of washing and reincubating treated cultures in antimicrobial-free media were investigated. Tetracycline and erythromycin inhibited C. trachomatis growth at concentrations attainable in human serum, although their actions were reversible and significantly higher concentrations were needed to \"cure\" 48-h infected cultures. On a weight basis, spectinomycin was relatively ineffective in inhibiting C. trachomatis growth. The minimal inhibitory concentration of penicillin measured by our assay procedures was higher than that reported by other investigators. The five assay procedures used in this study were reproducible, and our results indicate that we can obtain more pertinent information about the efficacy of an antimicrobial agent in controlling C. trachomatis growth by using a combination of these assays than by simple minimal inhibitory concentration determinations, as had been previously described by other investigators. In addition, we failed to demonstrate changes in tetracycline susceptibility of C. trachomatis isolates from two patients who had received tetracycline therapy."} {"id": "PMID:162542", "title": "Thymocyte-macrophage roles in autoimmune diseases.", "content": "Thymocytes and macrophages can be involved in the generation and perpetuation of autoimmune disorders in many ways. Evidence continues to mount for their active role. Although a significant association seems likely, one should remember that B cells and complement-directed granulocyte destruction may be equally if not more important. Furthermore, a combination of processes is not precluded by any fundamental biological law. Appropriate and effective therapy requires acceptance of this concept and further studies should attempt to define the interrelationships of these processes and focus upon methodology to determine their relative roles in a given situation.", "contents": "Thymocyte-macrophage roles in autoimmune diseases. Thymocytes and macrophages can be involved in the generation and perpetuation of autoimmune disorders in many ways. Evidence continues to mount for their active role. Although a significant association seems likely, one should remember that B cells and complement-directed granulocyte destruction may be equally if not more important. Furthermore, a combination of processes is not precluded by any fundamental biological law. Appropriate and effective therapy requires acceptance of this concept and further studies should attempt to define the interrelationships of these processes and focus upon methodology to determine their relative roles in a given situation."} {"id": "PMID:162543", "title": "Low back pain in the primary care setting.", "content": "A study of the natural presentation, course, and treatment of low back pain in the primary care setting was undertaken. One hundred and forty-four charts listing low back pain as a problem were reviewed at a family practice center for a period of one year. A profile of the patient evaluated by the primary care physician emerged, revealing a high incidence of associated weight problems (70 percent), psychologic problems (33 percent), and hypertension (19 percent). The rate of actual or suspected disc disease (1.4 percent) was much lower than that reported in series from referral centers. This study of low back pain in the primary care setting illustrates the usefulness of outpatient study in defining a problem category, recognizing disease as a symptom complex, suggesting modalities of treatment, and designing a curriculum for the primary care physician.", "contents": "Low back pain in the primary care setting. A study of the natural presentation, course, and treatment of low back pain in the primary care setting was undertaken. One hundred and forty-four charts listing low back pain as a problem were reviewed at a family practice center for a period of one year. A profile of the patient evaluated by the primary care physician emerged, revealing a high incidence of associated weight problems (70 percent), psychologic problems (33 percent), and hypertension (19 percent). The rate of actual or suspected disc disease (1.4 percent) was much lower than that reported in series from referral centers. This study of low back pain in the primary care setting illustrates the usefulness of outpatient study in defining a problem category, recognizing disease as a symptom complex, suggesting modalities of treatment, and designing a curriculum for the primary care physician."} {"id": "PMID:162544", "title": "Experimental evaluation of anterior chamber lenses fixated with Dacron.", "content": "Four new designs for anterior chamber intraocular lenses using Dacron fibers to achieve fixation were studied. After implantation in rabbit eyes, no lens dislocation occurred. Postmortem examination found firm Dacron adherence to iris tissue in all eyes. Clinically, no difference was noted in the amount of inflammation in eyes receiving a lens with or without Dacron. One new lens design was found to have substantial advantages over the other three models. However, a high incidence of corneal edema was found following insertion of all four experimental lenses.", "contents": "Experimental evaluation of anterior chamber lenses fixated with Dacron. Four new designs for anterior chamber intraocular lenses using Dacron fibers to achieve fixation were studied. After implantation in rabbit eyes, no lens dislocation occurred. Postmortem examination found firm Dacron adherence to iris tissue in all eyes. Clinically, no difference was noted in the amount of inflammation in eyes receiving a lens with or without Dacron. One new lens design was found to have substantial advantages over the other three models. However, a high incidence of corneal edema was found following insertion of all four experimental lenses."} {"id": "PMID:162545", "title": "The skin in Parkinson's disease.", "content": "The characteristic oily skin in individuals with parkinsonism has long been observed by clinicians. The oiliness seems to be associated with periods when the disease is most active. This seborrhea has been observed particularly in post-encephalitic parkinsonism, as well as in idiopathic paralysis agitans. It also occurs in phenothiazine-induced parkinsonism.", "contents": "The skin in Parkinson's disease. The characteristic oily skin in individuals with parkinsonism has long been observed by clinicians. The oiliness seems to be associated with periods when the disease is most active. This seborrhea has been observed particularly in post-encephalitic parkinsonism, as well as in idiopathic paralysis agitans. It also occurs in phenothiazine-induced parkinsonism."} {"id": "PMID:162547", "title": "Lumbar discography. Its value in diagnosis and treatment of lumbar disc lesions.", "content": "Lumbar discography has been performed in over 1500 patients at St. Luke's Episcopal Hospital, and a report concerning 683 cases has been previously published. The authors review an additional 199 cases, finding that decision making was influenced by discography in 155 cases (78%). A positive discogram was surgically confirmed in 111 patients (56%). In 14(7%) the disc was found to be normal at surgery. One hundred six patients (53%) had positive discograms with negative or equivocal myelogram. In 36 patients with a positive myelogram, the discogram was corroborative, although most patients with positive myelograms did not have discography. Sixty-nine patients (35%) did not have surgery.", "contents": "Lumbar discography. Its value in diagnosis and treatment of lumbar disc lesions. Lumbar discography has been performed in over 1500 patients at St. Luke's Episcopal Hospital, and a report concerning 683 cases has been previously published. The authors review an additional 199 cases, finding that decision making was influenced by discography in 155 cases (78%). A positive discogram was surgically confirmed in 111 patients (56%). In 14(7%) the disc was found to be normal at surgery. One hundred six patients (53%) had positive discograms with negative or equivocal myelogram. In 36 patients with a positive myelogram, the discogram was corroborative, although most patients with positive myelograms did not have discography. Sixty-nine patients (35%) did not have surgery."} {"id": "PMID:162546", "title": "A more precise diagnosis for low-back pain.", "content": "Five common syndromes productive of low-back and leg pain are presented as the basis for clinical investigation to arrive at an early and definite diagnosis in low-back pain problems. The five are posterior facet syndromes, sacroiliac-piriformis syndrome, herniated nucleus pulposus, central spinal stenosis, and nerve entrapment in the lateral recess. All may present with a common symptom complex of low-back, buttock, trochanteric, and posterior thigh pain. Specific details from history, physical, and radiographic examination may allow separation of these entities, but proof of diagnosis requires data from response to treatment, facet and nerve injection, myelography, discography, and computerized tomography (CT) scan.", "contents": "A more precise diagnosis for low-back pain. Five common syndromes productive of low-back and leg pain are presented as the basis for clinical investigation to arrive at an early and definite diagnosis in low-back pain problems. The five are posterior facet syndromes, sacroiliac-piriformis syndrome, herniated nucleus pulposus, central spinal stenosis, and nerve entrapment in the lateral recess. All may present with a common symptom complex of low-back, buttock, trochanteric, and posterior thigh pain. Specific details from history, physical, and radiographic examination may allow separation of these entities, but proof of diagnosis requires data from response to treatment, facet and nerve injection, myelography, discography, and computerized tomography (CT) scan."} {"id": "PMID:162548", "title": "Biomechanical testing as an aid to decision making in low-back pain patients.", "content": "Frequently, the diagnosis of disease of the low back is a difficult matter due to the multitude of factors affecting the patient's symptoms. In this report an attempt is made to use biomechanical testing to objectify certain aspects of the diagnostic process. Our philosophy is that a biomechanical assessment is one of the disciplines that should be brought to bear on the low-back pain patient. A group of biomechanical tests has been developed by adding quantitative measurement techniques to certain standard clinical maneuvers: muscle testing, range of motion testing, and straight leg raising testing. Moire fringe topography is employed for studying posture. Results of application of these techniques to 117 patients and 10 controls indicate potential utility in the method for epidemiologic and clinical research.", "contents": "Biomechanical testing as an aid to decision making in low-back pain patients. Frequently, the diagnosis of disease of the low back is a difficult matter due to the multitude of factors affecting the patient's symptoms. In this report an attempt is made to use biomechanical testing to objectify certain aspects of the diagnostic process. Our philosophy is that a biomechanical assessment is one of the disciplines that should be brought to bear on the low-back pain patient. A group of biomechanical tests has been developed by adding quantitative measurement techniques to certain standard clinical maneuvers: muscle testing, range of motion testing, and straight leg raising testing. Moire fringe topography is employed for studying posture. Results of application of these techniques to 117 patients and 10 controls indicate potential utility in the method for epidemiologic and clinical research."} {"id": "PMID:162549", "title": "A lumbar disc surgery predictive score card. A retrospective evaluation.", "content": "This report assessed the relationship between patient selection and the outcome of lumbar disc surgery. Patient selecting is assessed by means of a predictive scoring technique previously reported. Because of the dynamic and ever-changing status of the lumbar spine with the passage of time, patient selectivity seems to be less critical after 5 years. For the first 5 years, however, the outcome of lumbar disc surgery seems to be directly related to patient selectivity.", "contents": "A lumbar disc surgery predictive score card. A retrospective evaluation. This report assessed the relationship between patient selection and the outcome of lumbar disc surgery. Patient selecting is assessed by means of a predictive scoring technique previously reported. Because of the dynamic and ever-changing status of the lumbar spine with the passage of time, patient selectivity seems to be less critical after 5 years. For the first 5 years, however, the outcome of lumbar disc surgery seems to be directly related to patient selectivity."} {"id": "PMID:162550", "title": "The role of laminectomy, facet rhizotomy, and epidural steroids.", "content": "A retrospective review of the treatment of chronic back and extremity pain is presented. Laminectomy is most effective for pain secondary to direct compression of the neural elements. Treatment of pseudoradicular pain requires identification of the source of pain input. Facet rhizotomy is specific for pain arising from the posterior primary rami. Pain input from the recurrent sinuvertebral nerve requires epidural injection.", "contents": "The role of laminectomy, facet rhizotomy, and epidural steroids. A retrospective review of the treatment of chronic back and extremity pain is presented. Laminectomy is most effective for pain secondary to direct compression of the neural elements. Treatment of pseudoradicular pain requires identification of the source of pain input. Facet rhizotomy is specific for pain arising from the posterior primary rami. Pain input from the recurrent sinuvertebral nerve requires epidural injection."} {"id": "PMID:162551", "title": "Epidemiologic and clinical studies of long-term prognosis of low-back pain and sciatica.", "content": "In order to justify the selection of therapeutic measures for low-back pain and sciatica, epidemiologic and clinical studies were performed of the natural histories or the long-term prognosis of those symptoms. The main conclusions drawn in relation to decision making are as follows: low-back pain is more frequent than sciatica or intermittent claudication, but the latter is more disabling; acute attacks are generally more disabling than chronic pain, and the frequency may be more closely related to poor prognosis than the duration; radiologic findings are of little value in differentiating the incidence and degree of the symptoms during life; myelographic or peridurographic abnormalities do not always suggest poor prognosis.", "contents": "Epidemiologic and clinical studies of long-term prognosis of low-back pain and sciatica. In order to justify the selection of therapeutic measures for low-back pain and sciatica, epidemiologic and clinical studies were performed of the natural histories or the long-term prognosis of those symptoms. The main conclusions drawn in relation to decision making are as follows: low-back pain is more frequent than sciatica or intermittent claudication, but the latter is more disabling; acute attacks are generally more disabling than chronic pain, and the frequency may be more closely related to poor prognosis than the duration; radiologic findings are of little value in differentiating the incidence and degree of the symptoms during life; myelographic or peridurographic abnormalities do not always suggest poor prognosis."} {"id": "PMID:162552", "title": "Reliability and reproducibility of clinical findings in low-back pain.", "content": "The data obtained from the history and examination of patients with low-back pain and sciatica have been subjected to an observer variation analysis. Redesign of the proformata resulted in a reduction of the observer error from 33% to 18% for the history, but no improvement in the finding of a 30% observer error in the examination. The clinician has a simple choice: if he wishes to obtain a large amount of detailed information he must realize that much of it will be unreliable; if he is prepared to limit the information then he will increase its reliability.", "contents": "Reliability and reproducibility of clinical findings in low-back pain. The data obtained from the history and examination of patients with low-back pain and sciatica have been subjected to an observer variation analysis. Redesign of the proformata resulted in a reduction of the observer error from 33% to 18% for the history, but no improvement in the finding of a 30% observer error in the examination. The clinician has a simple choice: if he wishes to obtain a large amount of detailed information he must realize that much of it will be unreliable; if he is prepared to limit the information then he will increase its reliability."} {"id": "PMID:162556", "title": "Mitochondrial ATPase.", "content": "Considerable progress has been made in recent years in our understanding of the phosphorylating apparatus in mitochondria, chloroplasts, and bacteria. It has become clear that the structure and the function of the ATP synthesizing apparatus in these widely divergent organisms is similar if not virtually identical. The subunit composition of F1, its molecular architecture, the location and function of substrate binding sites, as well as putative control sites, understanding of the component parts of the oligomycin-sensitive ATPase complex, and the role of these components in the function of the complex all are under active investigation in many laboratories. The developing information and the new insights provided have begun to permit experimental approaches, at the molecular level, to the mode of action of the ATPase in electron-transport-coupled ATP synthesis.", "contents": "Mitochondrial ATPase. Considerable progress has been made in recent years in our understanding of the phosphorylating apparatus in mitochondria, chloroplasts, and bacteria. It has become clear that the structure and the function of the ATP synthesizing apparatus in these widely divergent organisms is similar if not virtually identical. The subunit composition of F1, its molecular architecture, the location and function of substrate binding sites, as well as putative control sites, understanding of the component parts of the oligomycin-sensitive ATPase complex, and the role of these components in the function of the complex all are under active investigation in many laboratories. The developing information and the new insights provided have begun to permit experimental approaches, at the molecular level, to the mode of action of the ATPase in electron-transport-coupled ATP synthesis."} {"id": "PMID:162557", "title": "Four cases of pregnancy with low estrogen production due to placental enzymatic deficiency.", "content": "4 cases of normal pregnancies associated with low estriol excretion and resulting in healthy infants are described, in which by in vitro studies on the placentas a steroid 3-sulfatase deficiency was found in 3 cases and a lack of activity of the aromatizing system was found in the 4th case. A reduced activity of the aromatizing system was also shown in one of the cases affected by steroid 3-sulfatase defect. The placental 3 beta-hydroxysteroid dehydrogenase, delta 4,5-isomerase system was measured in 3 cases and results were normal. The repetition of the specific lack of steroid 3-sulfatase was observed in 2 successive pregnancies of the same patient (case T.C.). It is interesting to note that, at variance with other reports, this patient delivered 2 fetuses, both female.", "contents": "Four cases of pregnancy with low estrogen production due to placental enzymatic deficiency. 4 cases of normal pregnancies associated with low estriol excretion and resulting in healthy infants are described, in which by in vitro studies on the placentas a steroid 3-sulfatase deficiency was found in 3 cases and a lack of activity of the aromatizing system was found in the 4th case. A reduced activity of the aromatizing system was also shown in one of the cases affected by steroid 3-sulfatase defect. The placental 3 beta-hydroxysteroid dehydrogenase, delta 4,5-isomerase system was measured in 3 cases and results were normal. The repetition of the specific lack of steroid 3-sulfatase was observed in 2 successive pregnancies of the same patient (case T.C.). It is interesting to note that, at variance with other reports, this patient delivered 2 fetuses, both female."} {"id": "PMID:162558", "title": "Rectus hematoma: a clinical diagnosis confirmed by ultrasound.", "content": "In 2 women the diagnosis of rectus hematoma could be established by ultrasound and the further clinical course. Echoscopy is stressed as a technique which is helpful to the patient and the clinician in avoiding unnecessary operations.", "contents": "Rectus hematoma: a clinical diagnosis confirmed by ultrasound. In 2 women the diagnosis of rectus hematoma could be established by ultrasound and the further clinical course. Echoscopy is stressed as a technique which is helpful to the patient and the clinician in avoiding unnecessary operations."} {"id": "PMID:162559", "title": "Enlarged left atrium causing possible false positive echocardiographic diagnosis of pericardial effusion.", "content": "Echocardiographic examination in a patient with IHSS, mitral insufficiency, and cardiomegaly suggested the possibility of a pericardial effusion. Echocardiographic M-mode scanning documented the continuity of the space posterior to the pericardium with an enlarged left atrium. Subsequent cineangiographic studies confirmed an enlarged left atrium and the absence of pericardial effusion. Left atrial enlargement may cause a false positive echocardiographic diagnosis of pericardial effusion.", "contents": "Enlarged left atrium causing possible false positive echocardiographic diagnosis of pericardial effusion. Echocardiographic examination in a patient with IHSS, mitral insufficiency, and cardiomegaly suggested the possibility of a pericardial effusion. Echocardiographic M-mode scanning documented the continuity of the space posterior to the pericardium with an enlarged left atrium. Subsequent cineangiographic studies confirmed an enlarged left atrium and the absence of pericardial effusion. Left atrial enlargement may cause a false positive echocardiographic diagnosis of pericardial effusion."} {"id": "PMID:162560", "title": "Oxalate, calcium uptake and ATPase activity of sarcoplasmic reticulum vesicles.", "content": "Ca++-uptake and Mg++-Ca++-dependent ATPase activity of skeletal muscle sarcoplasmic reticulum vesicles were reciprocally affected by increasing the oxalate concentration from 0 to 4 mM. At 0-0.1 mM oxalate approximately 17% of the calcium was removed by the vesicles from the medium while the ATPase activity was maximal (approximately 0.66 mumoles Pi mg-1 protein min-1). Between 0.1 to 0.2 mM oxalate the ATPase activity was reduced to one-fifth but the uptake rose sharply and 100% of the 45Ca++ was removed from the medium. The uptake was maintained at this level at oxalate concentrations greater than 0.4 mM but the ATPase activity remained inhibited. The kinetics of Ca++-uptake and ATPase activity were also differentially affected by oxalate. In the presence of oxalate, ruthenium red had only a very slight inhibitory effect on the calcium uptake. Addition of 0.1 mM EGTA removed 80% of the Ca++ from preloaded vesicles within 10 min. The formation of insoluble Ca-oxalate salt on the surface of the vesicle is suggested by these results. Calculations based on the Ksp of the calcium oxalate salt are presented to show its formation and the possible speciation of a Ca-oxalate complex which may affect the Ca++-uptake and ATPase activity.", "contents": "Oxalate, calcium uptake and ATPase activity of sarcoplasmic reticulum vesicles. Ca++-uptake and Mg++-Ca++-dependent ATPase activity of skeletal muscle sarcoplasmic reticulum vesicles were reciprocally affected by increasing the oxalate concentration from 0 to 4 mM. At 0-0.1 mM oxalate approximately 17% of the calcium was removed by the vesicles from the medium while the ATPase activity was maximal (approximately 0.66 mumoles Pi mg-1 protein min-1). Between 0.1 to 0.2 mM oxalate the ATPase activity was reduced to one-fifth but the uptake rose sharply and 100% of the 45Ca++ was removed from the medium. The uptake was maintained at this level at oxalate concentrations greater than 0.4 mM but the ATPase activity remained inhibited. The kinetics of Ca++-uptake and ATPase activity were also differentially affected by oxalate. In the presence of oxalate, ruthenium red had only a very slight inhibitory effect on the calcium uptake. Addition of 0.1 mM EGTA removed 80% of the Ca++ from preloaded vesicles within 10 min. The formation of insoluble Ca-oxalate salt on the surface of the vesicle is suggested by these results. Calculations based on the Ksp of the calcium oxalate salt are presented to show its formation and the possible speciation of a Ca-oxalate complex which may affect the Ca++-uptake and ATPase activity."} {"id": "PMID:162568", "title": "The clinical use and value of non-invasive diagnostic techniques in peripheral arterial occlusive disease.", "content": "The clinician confronted with the need for the objective evaluation of peripheral vascular problem has a variety of simple noninvasive techniques available which can prove highly useful in the early detection of occlusive disease, its functional assessment and in the selection of those problems which requires further definitive evaluation by angiographic methods. The non-invasive techniques offer the additional advantage of applicability to the serial evaluation of patients before and after surgical or medical therapy.", "contents": "The clinical use and value of non-invasive diagnostic techniques in peripheral arterial occlusive disease. The clinician confronted with the need for the objective evaluation of peripheral vascular problem has a variety of simple noninvasive techniques available which can prove highly useful in the early detection of occlusive disease, its functional assessment and in the selection of those problems which requires further definitive evaluation by angiographic methods. The non-invasive techniques offer the additional advantage of applicability to the serial evaluation of patients before and after surgical or medical therapy."} {"id": "PMID:162570", "title": "Platelet lysis and aggregation in shear fields.", "content": "A rotational viscometer was used to study the effects of shear stress on platelets in human platelet-rich plasma (PRP). For 5-min exposure times, shear stresses above 160 dynes/cm2 induced platelet lysis (as determined by release of platelet lactic dehydrogenase). For 30-s exposure times, shear stresses greater than 600 dynes/cm2 were required to induce platelet lysis. The platelet counts of sheared PRP were decreased to as low as one-fifth the original count due largely to shear-induced aggregation. The count is a minimum at intermediate stress levels (200-400 dynes/cm2). Higher stresses induce disaggregation as well as lysis. The diminution in the counts was partially reversed in 2 h incubation after cessation of shearing. Experiments were carried out with three different viscometer configurations so that the shear stress and the solid surface area access could be varied independently. Surface access was not a significant variable in the conditions of the experiments. Thus aggregation and lysis may be induced by stress effects alone as well as by solid surface effects. The results also show that the response of platelets to shear stress is strongly dependent on exposure time. Platelets are much less resistant to shear stress than red cells for relatively long exposure times. However, the converse is true for very short exposure times.", "contents": "Platelet lysis and aggregation in shear fields. A rotational viscometer was used to study the effects of shear stress on platelets in human platelet-rich plasma (PRP). For 5-min exposure times, shear stresses above 160 dynes/cm2 induced platelet lysis (as determined by release of platelet lactic dehydrogenase). For 30-s exposure times, shear stresses greater than 600 dynes/cm2 were required to induce platelet lysis. The platelet counts of sheared PRP were decreased to as low as one-fifth the original count due largely to shear-induced aggregation. The count is a minimum at intermediate stress levels (200-400 dynes/cm2). Higher stresses induce disaggregation as well as lysis. The diminution in the counts was partially reversed in 2 h incubation after cessation of shearing. Experiments were carried out with three different viscometer configurations so that the shear stress and the solid surface area access could be varied independently. Surface access was not a significant variable in the conditions of the experiments. Thus aggregation and lysis may be induced by stress effects alone as well as by solid surface effects. The results also show that the response of platelets to shear stress is strongly dependent on exposure time. Platelets are much less resistant to shear stress than red cells for relatively long exposure times. However, the converse is true for very short exposure times."} {"id": "PMID:162572", "title": "Clinical studies on peripheral hemodynamics in arterial hypertension.", "content": "Digital blood pressure and flow were measured in both normal subjects and patients with essential hypertension by means of the apparatus which have been recently devised, and peripheral vascular resistance was calculated according to Poiseuille's law in order to compare them. 1. Digital blood pressure is higher, the digital blood flow is less and the peripheral vascular resistance is stronger in patients with essential hypertension than in normotensives. 2. Hypertensive patients with ischemic heart disease, calcification of the aortic arch, left ventricular hypertrophy and heart size greater than 53% of the cardio-thoracic ratio were higher in the digital pressure, less in the digital flow, and stronger in the peripheral vascular resistance than those without these findings of the heart and the aortic arch. 3. The curve of relationship obtained from many cases of both normotensives and hypertensives between the digital blood flow and the peripheral vascular resistance forms a hyperbola. 4. Peripheral vascular resistance in both normotensives and hypertensives increased gradually with age up to 50-60 years, and decreased slightly thereafter. The resistance was stronger in patients with essential hypertension than in normotensives through all ages.", "contents": "Clinical studies on peripheral hemodynamics in arterial hypertension. Digital blood pressure and flow were measured in both normal subjects and patients with essential hypertension by means of the apparatus which have been recently devised, and peripheral vascular resistance was calculated according to Poiseuille's law in order to compare them. 1. Digital blood pressure is higher, the digital blood flow is less and the peripheral vascular resistance is stronger in patients with essential hypertension than in normotensives. 2. Hypertensive patients with ischemic heart disease, calcification of the aortic arch, left ventricular hypertrophy and heart size greater than 53% of the cardio-thoracic ratio were higher in the digital pressure, less in the digital flow, and stronger in the peripheral vascular resistance than those without these findings of the heart and the aortic arch. 3. The curve of relationship obtained from many cases of both normotensives and hypertensives between the digital blood flow and the peripheral vascular resistance forms a hyperbola. 4. Peripheral vascular resistance in both normotensives and hypertensives increased gradually with age up to 50-60 years, and decreased slightly thereafter. The resistance was stronger in patients with essential hypertension than in normotensives through all ages."} {"id": "PMID:162577", "title": "Muscle structure and function in the goose, quail, pheasant, guinea hen, and chicken.", "content": "1. Metabolic functions, fiber composition and, in some cases, mitochondrial morphology have been investigated in the pectoralis major and sartorius of the goose, quail, pheasant, guinea-hen, broiler chicken and laying hen. 2. In the pectoralis only two types of fibers, red and white twitch fibers, are found in all birds studied except in the quail, where a third twitch fiber also occurs. Red fibers form the main part in the quail and goose, white fibers in the rest. In the sartorius at least three types of fibers, two twitch and one tonus are found in all birds except in the guinea-hen where only two fibers can be found. 3. The metabolic pattern of the muscles, based on determination of specific activities of metabolic key enzymes, varies greatly among the birds. Three groups can be discerned from the ratio between aerobic and anaerobic activities or between fatty acid oxidation and carbohydrate metabolism. The metabolic patterns are reflected in the fiber combinations of the muscles. 4. The size and number of the mitochondria vary among different animals and different fiber types. The metabolism of red and white fibers is discussed.", "contents": "Muscle structure and function in the goose, quail, pheasant, guinea hen, and chicken. 1. Metabolic functions, fiber composition and, in some cases, mitochondrial morphology have been investigated in the pectoralis major and sartorius of the goose, quail, pheasant, guinea-hen, broiler chicken and laying hen. 2. In the pectoralis only two types of fibers, red and white twitch fibers, are found in all birds studied except in the quail, where a third twitch fiber also occurs. Red fibers form the main part in the quail and goose, white fibers in the rest. In the sartorius at least three types of fibers, two twitch and one tonus are found in all birds except in the guinea-hen where only two fibers can be found. 3. The metabolic pattern of the muscles, based on determination of specific activities of metabolic key enzymes, varies greatly among the birds. Three groups can be discerned from the ratio between aerobic and anaerobic activities or between fatty acid oxidation and carbohydrate metabolism. The metabolic patterns are reflected in the fiber combinations of the muscles. 4. The size and number of the mitochondria vary among different animals and different fiber types. The metabolism of red and white fibers is discussed."} {"id": "PMID:162578", "title": "A comparative study of brain Ca2+-ATPases.", "content": "1. Particulate brain ATPases from various vertebrates were optimally activated by Ca2+, Mg2+ or Mn2+. 2. Specific enzyme activity with AT32P as substrate was low in lower vertebrates and increased on the evolutionary scale. 3. The properties of the brain ATPases suggested that most of the activity was associated with plasma membrane ecto-ATPase.", "contents": "A comparative study of brain Ca2+-ATPases. 1. Particulate brain ATPases from various vertebrates were optimally activated by Ca2+, Mg2+ or Mn2+. 2. Specific enzyme activity with AT32P as substrate was low in lower vertebrates and increased on the evolutionary scale. 3. The properties of the brain ATPases suggested that most of the activity was associated with plasma membrane ecto-ATPase."} {"id": "PMID:162579", "title": "Changes in the specific activity of N-acetyl-beta-D-hexosaminidase in the rat epididymis with age.", "content": "The specific activity of the lysosomal enzyme N-acetyl-beta-D-hexosaminidase was determined in the caput and cauda of the epididymis of rats as a function of age. The activity peaks at six weeks of age in both parts of the epididymis but is higher in the cauda. The results indicate a relationship between changes occurring in sperm in the epididymis and the lysosomal enzymes.", "contents": "Changes in the specific activity of N-acetyl-beta-D-hexosaminidase in the rat epididymis with age. The specific activity of the lysosomal enzyme N-acetyl-beta-D-hexosaminidase was determined in the caput and cauda of the epididymis of rats as a function of age. The activity peaks at six weeks of age in both parts of the epididymis but is higher in the cauda. The results indicate a relationship between changes occurring in sperm in the epididymis and the lysosomal enzymes."} {"id": "PMID:162580", "title": "Effects of high hydrostatic pressures on the activity of the membrane ATPases of some organs implicated in hydromineral regulation.", "content": "1. The effects of high hydrostatic pressures have been studied on the ATPases extracted from tissues implicated in iono- and osmoregulation of a frog and various teleostean fishes. Pressure affects enzyme activity in the same qualitative way, whatever the tissue and the species considered. 2. The Mg2+ ATPase activity is maximally enhanced at 250 kg/cm2. A slight inhibition is observed at higher pressures up to 1000 kg/cm2. 3. The (Na+ + K+)ATPase is little affected by low pressures but strongly inhibited at 500 kg/cm2 and more. 4. The results are discussed in terms of pressure effects on the recently described protein-lipid interaction linked to ATPase activity.", "contents": "Effects of high hydrostatic pressures on the activity of the membrane ATPases of some organs implicated in hydromineral regulation. 1. The effects of high hydrostatic pressures have been studied on the ATPases extracted from tissues implicated in iono- and osmoregulation of a frog and various teleostean fishes. Pressure affects enzyme activity in the same qualitative way, whatever the tissue and the species considered. 2. The Mg2+ ATPase activity is maximally enhanced at 250 kg/cm2. A slight inhibition is observed at higher pressures up to 1000 kg/cm2. 3. The (Na+ + K+)ATPase is little affected by low pressures but strongly inhibited at 500 kg/cm2 and more. 4. The results are discussed in terms of pressure effects on the recently described protein-lipid interaction linked to ATPase activity."} {"id": "PMID:162581", "title": "Control of ciliary activity in paramecium--IV. Ca2+ modification of Mg2+ dependent dynein ATPase activity.", "content": "1. Dynein proteins were solubilized from demembranated cilia of Paramecium by extraction at high ionic strength. 2. Mg2+-dependent ATPase (EC 3.6.1.3) activity of crude dynein extracts was inhibited by micromolar concentrations of Ca2+ ions. 3. Sepharose 4B chromatography of the crude extracts yields three dynein fractions. The major fraction contains a single protein and is insensitive to Ca2+ ions. Two other fractions, both heterogeneous in composition, show opposing Ca2+ ion sensitivity expressed as a Ca2+ dependent alteration in MgATP2- dependent ATPase activity. The Ca2+ ion sensitive forms show altered electrophoretic mobility on native polyacrylamide gels in the presence and absence of Ca2+ ions. 4. The data provides evidence for a Ca2+ ion dependent concomitant alteration in both molecular form and hydrolytic activity of the dyneins. The results are discussed in terms of a possible molecular mechanism for Ca ion regulation of ciliary activity in terms of the sliding microtubule model.", "contents": "Control of ciliary activity in paramecium--IV. Ca2+ modification of Mg2+ dependent dynein ATPase activity. 1. Dynein proteins were solubilized from demembranated cilia of Paramecium by extraction at high ionic strength. 2. Mg2+-dependent ATPase (EC 3.6.1.3) activity of crude dynein extracts was inhibited by micromolar concentrations of Ca2+ ions. 3. Sepharose 4B chromatography of the crude extracts yields three dynein fractions. The major fraction contains a single protein and is insensitive to Ca2+ ions. Two other fractions, both heterogeneous in composition, show opposing Ca2+ ion sensitivity expressed as a Ca2+ dependent alteration in MgATP2- dependent ATPase activity. The Ca2+ ion sensitive forms show altered electrophoretic mobility on native polyacrylamide gels in the presence and absence of Ca2+ ions. 4. The data provides evidence for a Ca2+ ion dependent concomitant alteration in both molecular form and hydrolytic activity of the dyneins. The results are discussed in terms of a possible molecular mechanism for Ca ion regulation of ciliary activity in terms of the sliding microtubule model."} {"id": "PMID:162576", "title": "Study of cortical spindles during sleep in the rat.", "content": "A systematic analysis of the dorsally accessible cortical areas has been undertaken so as to study the space-time distribution, the intrinsic characteristics and the physiological appearance modalities of cortical spindles in the rat. After falling asleep, the animal presents anterior spindles of which the number, duration and amplitude increase as sleep with slow waves deepens. These spindles are fully developed during intermediate state which precedes and follows paradoxical sleep, where they are associated with a theta rhythm in the hippocampus and the visual cortex. These spindles, at their maximum in anterior regions, lose intensity as one approaches the cerebellum. Uniquely during slow wave phase of sleep, the rat presents posterior spindles which are predominant in the occipital region, are less marked in parietal and cerebellar regions and disappear in the frontal cortex. Less frequent than anterior spindles, they are significantly distinguished by their lower amplitude, higher frequency and shorter duration.", "contents": "Study of cortical spindles during sleep in the rat. A systematic analysis of the dorsally accessible cortical areas has been undertaken so as to study the space-time distribution, the intrinsic characteristics and the physiological appearance modalities of cortical spindles in the rat. After falling asleep, the animal presents anterior spindles of which the number, duration and amplitude increase as sleep with slow waves deepens. These spindles are fully developed during intermediate state which precedes and follows paradoxical sleep, where they are associated with a theta rhythm in the hippocampus and the visual cortex. These spindles, at their maximum in anterior regions, lose intensity as one approaches the cerebellum. Uniquely during slow wave phase of sleep, the rat presents posterior spindles which are predominant in the occipital region, are less marked in parietal and cerebellar regions and disappear in the frontal cortex. Less frequent than anterior spindles, they are significantly distinguished by their lower amplitude, higher frequency and shorter duration."} {"id": "PMID:162583", "title": "Adenosine triphosphatase activities in Trypanosoma cruzi.", "content": "1. Subcellular fractions obtained from epimastigotes of Trypanosoma cruzi, disrupted by three different procedures, contained in addition to the already known Mg2+-activated adenosine triphosphatase (ATPase; E.C.3.6.1.4), a Ca2+-ATPase activity. 2. The Ca2+-ATPase (a) was activated by low concentrations of CaCl2 (apparent Ka, 80 microM); (b) had a Km for ATP of 0.6 mM (at 1 mM CaCl2, pH 8.0); (c) presented a broad pH curve (optimum 7.1-8.6); and (d) was insensitive to oligomycin concentrations which inhibited the Mg2+-ATPase present in the same preparations. 3. All attempts to find a (Na+-K+)-activated, ouabain-inhibited, ATPase have been unsuccessful, in spite of the fact that living epimastigoes of T. cruzi are able to concentrate K+ and exclude Na+ from the medium.", "contents": "Adenosine triphosphatase activities in Trypanosoma cruzi. 1. Subcellular fractions obtained from epimastigotes of Trypanosoma cruzi, disrupted by three different procedures, contained in addition to the already known Mg2+-activated adenosine triphosphatase (ATPase; E.C.3.6.1.4), a Ca2+-ATPase activity. 2. The Ca2+-ATPase (a) was activated by low concentrations of CaCl2 (apparent Ka, 80 microM); (b) had a Km for ATP of 0.6 mM (at 1 mM CaCl2, pH 8.0); (c) presented a broad pH curve (optimum 7.1-8.6); and (d) was insensitive to oligomycin concentrations which inhibited the Mg2+-ATPase present in the same preparations. 3. All attempts to find a (Na+-K+)-activated, ouabain-inhibited, ATPase have been unsuccessful, in spite of the fact that living epimastigoes of T. cruzi are able to concentrate K+ and exclude Na+ from the medium."} {"id": "PMID:162584", "title": "Solubilization and some properties of the Mg2+-activated adenosine triphosphatase from Trypanosoma cruzi.", "content": "1. Grinding of epimastigotes of Trypanosoma cruzi with glass powder in a mortar yielded a Mg2+-activated adenosine triphosphatase (ATPase) preparation which was highly sensitive to oligomycin. 2. Chloroform treatment of the particles resulted in the solubilization of an ATPase which was (a) activated by MgCl2; (b) slightly inhibited by CaCl2; (c) activated by sulphite and bisulphite; (d) had an optimum pH of 7.6; and (e) had a Km for ATP of 2.1 mM (in the presence of 4 mM MgCl2). 3. The solubilized enzyme was insensitive to oligomycin and leucinostatin, which inhibited the membrane-bound ATPase, though inhibited by efrapeptin and quercetin. 4. The results indicate that the chloroform-extracted enzyme is a soluble F1-ATPase similar to those isolated from mammalian mitochondria.", "contents": "Solubilization and some properties of the Mg2+-activated adenosine triphosphatase from Trypanosoma cruzi. 1. Grinding of epimastigotes of Trypanosoma cruzi with glass powder in a mortar yielded a Mg2+-activated adenosine triphosphatase (ATPase) preparation which was highly sensitive to oligomycin. 2. Chloroform treatment of the particles resulted in the solubilization of an ATPase which was (a) activated by MgCl2; (b) slightly inhibited by CaCl2; (c) activated by sulphite and bisulphite; (d) had an optimum pH of 7.6; and (e) had a Km for ATP of 2.1 mM (in the presence of 4 mM MgCl2). 3. The solubilized enzyme was insensitive to oligomycin and leucinostatin, which inhibited the membrane-bound ATPase, though inhibited by efrapeptin and quercetin. 4. The results indicate that the chloroform-extracted enzyme is a soluble F1-ATPase similar to those isolated from mammalian mitochondria."} {"id": "PMID:162585", "title": "Purification and properties of two isoenzymes of beta-N-acetylhexosaminidase from Turbo cornutus.", "content": "1. beta-N-acetylhexosaminidase isoenzymes from the gastropod, T. cornutus, were purified and their properties studied. 2. The two isoenzymes, designated A and B were separated by DEAE-Sephadex column chromatography and further purified by CM-cellulose, Concanavalin-A-Sepharose-4B and Sephadex G-200 column chromatography. 3. beta-N-Acetylhexosaminidase A and B were purified 416 and 208 fold, with yields of 10.6 and 5.1%, respectively. 4. The two isoenzymes appear homogeneous on polyacrylamide gel electrophoresis, with the A form migrating faster towards the anode than the B form. 5. The purified isoenzymes are virtually free of all other common glycosidase contaminations. 6. The apparent molecular weight of both beta-N-acetylhexosaminidase A and B is about 100,000 when estimated with gel filtration column chromatography and the pH optimum for both is 4.0. 7. Both beta-N-acetylhexosaminidase isoenzyme activities are stimulated by Cl-, Br-, F-, I- and NO3-, and inhibited by Hg+, Ag+, Fe3+, N-acetylglucosamine and N-acetylgalactosamine. 8. The Km values of beta-N-acetylhexosaminidase A and B for the substrate p-nitrophenyl-beta-2-acetamide-2-deoxy-D-glucopyranoside were 2.9 and 3.2 mM, respectively.", "contents": "Purification and properties of two isoenzymes of beta-N-acetylhexosaminidase from Turbo cornutus. 1. beta-N-acetylhexosaminidase isoenzymes from the gastropod, T. cornutus, were purified and their properties studied. 2. The two isoenzymes, designated A and B were separated by DEAE-Sephadex column chromatography and further purified by CM-cellulose, Concanavalin-A-Sepharose-4B and Sephadex G-200 column chromatography. 3. beta-N-Acetylhexosaminidase A and B were purified 416 and 208 fold, with yields of 10.6 and 5.1%, respectively. 4. The two isoenzymes appear homogeneous on polyacrylamide gel electrophoresis, with the A form migrating faster towards the anode than the B form. 5. The purified isoenzymes are virtually free of all other common glycosidase contaminations. 6. The apparent molecular weight of both beta-N-acetylhexosaminidase A and B is about 100,000 when estimated with gel filtration column chromatography and the pH optimum for both is 4.0. 7. Both beta-N-acetylhexosaminidase isoenzyme activities are stimulated by Cl-, Br-, F-, I- and NO3-, and inhibited by Hg+, Ag+, Fe3+, N-acetylglucosamine and N-acetylgalactosamine. 8. The Km values of beta-N-acetylhexosaminidase A and B for the substrate p-nitrophenyl-beta-2-acetamide-2-deoxy-D-glucopyranoside were 2.9 and 3.2 mM, respectively."} {"id": "PMID:162586", "title": "Structural comparison of hexosaminidases in primates.", "content": "1. beta-Hexosaminidase (hex) structure was compared in various primates, using thin-layer isoelectric focusing on polyacrylamide gels and quantitative microcomplement fixation. 2. Isoelectric focusing revealed no intraspecies differences and similar interspecies patterns. 3. Hex A and B are evolving at a moderate, but equal, rate and in a manner consistent with accepted phylogenetic patterns. 4. Quantitative microcomplement fixation revealed a closer homology between human hex A and chimpanzee A or human hex B and chimpanzee hex B than between human hex A and human hex B.", "contents": "Structural comparison of hexosaminidases in primates. 1. beta-Hexosaminidase (hex) structure was compared in various primates, using thin-layer isoelectric focusing on polyacrylamide gels and quantitative microcomplement fixation. 2. Isoelectric focusing revealed no intraspecies differences and similar interspecies patterns. 3. Hex A and B are evolving at a moderate, but equal, rate and in a manner consistent with accepted phylogenetic patterns. 4. Quantitative microcomplement fixation revealed a closer homology between human hex A and chimpanzee A or human hex B and chimpanzee hex B than between human hex A and human hex B."} {"id": "PMID:162582", "title": "[Chagas myocardiopathy. Presentation of a case].", "content": "1. The first case of Chagasic Miocardiopathy with complete immunologic confirmation is described. 2. The clinical, radiological, and electrocardiographic basis of the case were analyzed. 3. The specificity and the sensibility to the different seroimmunologic reactions in the Chagasic Disease was discussed. 4. An emphasis is placed on the fact that Chagas illness is not a rare entity in the Mexican Republic. 5. We recommend that a campaign of serologic investigation is begin to discover the true frequency of this illness.", "contents": "[Chagas myocardiopathy. Presentation of a case]. 1. The first case of Chagasic Miocardiopathy with complete immunologic confirmation is described. 2. The clinical, radiological, and electrocardiographic basis of the case were analyzed. 3. The specificity and the sensibility to the different seroimmunologic reactions in the Chagasic Disease was discussed. 4. An emphasis is placed on the fact that Chagas illness is not a rare entity in the Mexican Republic. 5. We recommend that a campaign of serologic investigation is begin to discover the true frequency of this illness."} {"id": "PMID:162587", "title": "Effects of acute starvation on carbohydrate metabolism in rat salivary glands.", "content": "1. Effects of acute starvation on enzymes of carbohydrate metabolism were determined in rat submandibular and parotid glands. 2. Activities of glycolytic enzymes were high in submandibular gland, but those of pentose phosphate pathway and glycogen metabolism were high in parotid gland. 3. Enzyme activities were lowered by acute starvation. Refeeding the rats with solid diet restored the enzyme activities, but with liquid diet, only partial recoveries were found in submandibular gland.", "contents": "Effects of acute starvation on carbohydrate metabolism in rat salivary glands. 1. Effects of acute starvation on enzymes of carbohydrate metabolism were determined in rat submandibular and parotid glands. 2. Activities of glycolytic enzymes were high in submandibular gland, but those of pentose phosphate pathway and glycogen metabolism were high in parotid gland. 3. Enzyme activities were lowered by acute starvation. Refeeding the rats with solid diet restored the enzyme activities, but with liquid diet, only partial recoveries were found in submandibular gland."} {"id": "PMID:162588", "title": "Ca2+-activated adenosinetriphosphatase activity in the gills of freshwater-and seawater-adapted eels (Anguilla rostrata).", "content": "1. Ca2+ -activated ATPase activity was higher in the gills of freshwater acclimated eels than in the gills of seawater acclimated eels. 2. The properties of the enzyme and the amount of protein extracted were identical in freshwater and seawater acclimated eels.", "contents": "Ca2+-activated adenosinetriphosphatase activity in the gills of freshwater-and seawater-adapted eels (Anguilla rostrata). 1. Ca2+ -activated ATPase activity was higher in the gills of freshwater acclimated eels than in the gills of seawater acclimated eels. 2. The properties of the enzyme and the amount of protein extracted were identical in freshwater and seawater acclimated eels."} {"id": "PMID:162589", "title": "Isoenzyme patterns of cultured Trypanosoma cruzi: changes after prolonged subculture.", "content": "1. The isoenzyme patterns of four soluble enzymes in seven stocks of T. cruzi were determined by electrophoresis. According to their patterns they could be classified into four sets. 2. The isoenzyme patterns of two stocks were influenced by the number of subcultures. 3. Five stocks from man are distinct from those derived from a silvatic reservoir. 4. Since the isoenzyme patterns of a stock isolated from a patient with acute disease were similar to those of a silvatic reservoir, its recent introduction into the domiciliary cycle is postulated.", "contents": "Isoenzyme patterns of cultured Trypanosoma cruzi: changes after prolonged subculture. 1. The isoenzyme patterns of four soluble enzymes in seven stocks of T. cruzi were determined by electrophoresis. According to their patterns they could be classified into four sets. 2. The isoenzyme patterns of two stocks were influenced by the number of subcultures. 3. Five stocks from man are distinct from those derived from a silvatic reservoir. 4. Since the isoenzyme patterns of a stock isolated from a patient with acute disease were similar to those of a silvatic reservoir, its recent introduction into the domiciliary cycle is postulated."} {"id": "PMID:162590", "title": "ATPase stimulated by Na+ or K+ in gills of the freshwater mussel Anodonta.", "content": "1. Microsomal preparations from the gills of the freshwater mussel anodonta cygnea cellensis show Mg2+ -dependent Na+ - or K+ -stimulated ATPase activity, which is not inhibited by ouabain. 2. Na+ - or Ka+ -ATPase activity is decreased by Ca2+, acetylcholine, choline, and tetramethylammonium, but slightly increased by ethyl alcohol. 3. It is tentatively suggested that Na+ - or K+ -ATPase is involved in the mechanism of active monovalent cation uptake through the gills of freshwater mussels.", "contents": "ATPase stimulated by Na+ or K+ in gills of the freshwater mussel Anodonta. 1. Microsomal preparations from the gills of the freshwater mussel anodonta cygnea cellensis show Mg2+ -dependent Na+ - or K+ -stimulated ATPase activity, which is not inhibited by ouabain. 2. Na+ - or Ka+ -ATPase activity is decreased by Ca2+, acetylcholine, choline, and tetramethylammonium, but slightly increased by ethyl alcohol. 3. It is tentatively suggested that Na+ - or K+ -ATPase is involved in the mechanism of active monovalent cation uptake through the gills of freshwater mussels."} {"id": "PMID:162600", "title": "Pyrolytic carbon-coated Dacron grafts.", "content": "A new pyrolytic carbon surface (ULTI) was tested on a loosely knitted dacron substrate in dogs. Patency was 97.5% as compared with a control of 33%. Physical properties of the dacron were not altered by the ULTI carbon deposition process. This modified pyrolytic carbon on a dacron substrate is a very promising vascular biomaterial for small vessel replacement.", "contents": "Pyrolytic carbon-coated Dacron grafts. A new pyrolytic carbon surface (ULTI) was tested on a loosely knitted dacron substrate in dogs. Patency was 97.5% as compared with a control of 33%. Physical properties of the dacron were not altered by the ULTI carbon deposition process. This modified pyrolytic carbon on a dacron substrate is a very promising vascular biomaterial for small vessel replacement."} {"id": "PMID:162614", "title": "Long-stay patients in the London Borough of Tower Hamlets.", "content": "In September 1974 a study was made of all residents of the East London Borough of Tower Hamlets, aged 65 or more, who were known to have been receiving continuous medical and nursing care in hospital for more than a year. There were 91 geriatric and approximately 100 psychiatric patients, representing just under 1 per cent of the population over 65. Eighty geriatric and 15 psychiatric patients were studied in detail. Physical and mental incapacity were assessed on the basis of performance of practical tasks and simple tests of ability, and social incapacity from a study of social circumstances. Both geriatric and psychiatric patients showed extreme disability. Geriatric patients showed physical and intellectual incapacity, psychiatric patients intellectual incapacity. The commonest diagnosis among geriatric patients was dementia (70 per cent). Social factors, while unfavourable, did not in themselves account for prolonged hospital stay. The finding of only a very small number of long-stay patients handicapped by physical disability alone suggests that the majority of such patients are at home.", "contents": "Long-stay patients in the London Borough of Tower Hamlets. In September 1974 a study was made of all residents of the East London Borough of Tower Hamlets, aged 65 or more, who were known to have been receiving continuous medical and nursing care in hospital for more than a year. There were 91 geriatric and approximately 100 psychiatric patients, representing just under 1 per cent of the population over 65. Eighty geriatric and 15 psychiatric patients were studied in detail. Physical and mental incapacity were assessed on the basis of performance of practical tasks and simple tests of ability, and social incapacity from a study of social circumstances. Both geriatric and psychiatric patients showed extreme disability. Geriatric patients showed physical and intellectual incapacity, psychiatric patients intellectual incapacity. The commonest diagnosis among geriatric patients was dementia (70 per cent). Social factors, while unfavourable, did not in themselves account for prolonged hospital stay. The finding of only a very small number of long-stay patients handicapped by physical disability alone suggests that the majority of such patients are at home."} {"id": "PMID:162616", "title": "Enzyme typing of human hair roots.", "content": "Sufficient phosphoglucomutase activity was found to be present in plucked hair noses bearing either fragmentary or complete outer root sheaths to enable typing of individual roots by starch-gel electrophoresis. Hair roots collected by brushing were found to contain very little PGM activity. Other isoenzyme systems were detected in hair roots but in insufficient quantities to make typing feasible.", "contents": "Enzyme typing of human hair roots. Sufficient phosphoglucomutase activity was found to be present in plucked hair noses bearing either fragmentary or complete outer root sheaths to enable typing of individual roots by starch-gel electrophoresis. Hair roots collected by brushing were found to contain very little PGM activity. Other isoenzyme systems were detected in hair roots but in insufficient quantities to make typing feasible."} {"id": "PMID:162619", "title": "[Report of a cased of carcinoma of the hypopharynx successfully treated by immediate pharyngogastrostomy (author's transl)].", "content": "The treatment of carcinoma of the lower part of the pharynx and upper oesophagus presents many difficulties. One of the outstanding problems being that of repair of the defect after excision of the pharyngo-oesophageal portion of the alimentary tract. This paper describes an operation in which the mobilized stomach is transposed after blunt dissection of the oesophagus via a posterior mediastinal tunnel without thoracotomy to a position high in the neck, with anastomosis of the fundus to the pharynx at the level of vallecula. This type of oesophagectomy was first tried bei Turner 1936 for carcinoma of the thoracic oesophagus. The main advantage of this form of repair is that it can restore normal swallowing within a few days in this difficult clinical situation.", "contents": "[Report of a cased of carcinoma of the hypopharynx successfully treated by immediate pharyngogastrostomy (author's transl)]. The treatment of carcinoma of the lower part of the pharynx and upper oesophagus presents many difficulties. One of the outstanding problems being that of repair of the defect after excision of the pharyngo-oesophageal portion of the alimentary tract. This paper describes an operation in which the mobilized stomach is transposed after blunt dissection of the oesophagus via a posterior mediastinal tunnel without thoracotomy to a position high in the neck, with anastomosis of the fundus to the pharynx at the level of vallecula. This type of oesophagectomy was first tried bei Turner 1936 for carcinoma of the thoracic oesophagus. The main advantage of this form of repair is that it can restore normal swallowing within a few days in this difficult clinical situation."} {"id": "PMID:162620", "title": "[The immunglobulin-content of human parotid saliva (author's transl)].", "content": "By means of radial immundiffusion, the content of IgA, IgG, IgM and IgE in 22 healthy persons was measured. The parotid saliva has been collected under standardized stimulation-conditions in 10 minutes-fractions during a time of 30 minutes. While IgM and IgE could not be found with this method, IgA and IgG were present in a concentration easy to be measured. For the two immunglobulins, a different and characteristical change in their concentration was found during stimulation. This difference can be explained by the different origin of the substances.", "contents": "[The immunglobulin-content of human parotid saliva (author's transl)]. By means of radial immundiffusion, the content of IgA, IgG, IgM and IgE in 22 healthy persons was measured. The parotid saliva has been collected under standardized stimulation-conditions in 10 minutes-fractions during a time of 30 minutes. While IgM and IgE could not be found with this method, IgA and IgG were present in a concentration easy to be measured. For the two immunglobulins, a different and characteristical change in their concentration was found during stimulation. This difference can be explained by the different origin of the substances."} {"id": "PMID:162621", "title": "Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of \"compensatory\" muscle hypertrophy in the rat.", "content": "1. Maximum compensatory hypertrophy of the soleus and plantaris muscle in male rats is attained seven days after tenotomy of the gastrocnemius muscle (39% and 9% respectively). When tenotomy of the gastrocnemius was performed seven days ater hypophysectomy, hypertrophy in these two muscles was aproximately half that found in control animals. 2. After 81-day castration of young male rats the weight of the saleus and plantaris was reduced and hypertrophy following tenotomy of the gastrocneumius muscle did not develop. 3. Chronically castrated rats received testosterone two weeks prior to tenotomy of the gastrocnemius and a week during the muscle hypertrophy phase. Hypertrophy of the soleus in castrated rats which had received testosterone seven days after tenotomy of the gastrocnemius was 25% as compared with muscles of castrated animals. The corresponding value in the plantaris muscle was 10%. 4. These results indicate that even calf muscles of the rat, namely the soleus and plantaris muscles, are significantly affected by testosterone under these conditions, although it is not, as yet, clear whether its action is direct or indirect.", "contents": "Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of \"compensatory\" muscle hypertrophy in the rat. 1. Maximum compensatory hypertrophy of the soleus and plantaris muscle in male rats is attained seven days after tenotomy of the gastrocnemius muscle (39% and 9% respectively). When tenotomy of the gastrocnemius was performed seven days ater hypophysectomy, hypertrophy in these two muscles was aproximately half that found in control animals. 2. After 81-day castration of young male rats the weight of the saleus and plantaris was reduced and hypertrophy following tenotomy of the gastrocneumius muscle did not develop. 3. Chronically castrated rats received testosterone two weeks prior to tenotomy of the gastrocnemius and a week during the muscle hypertrophy phase. Hypertrophy of the soleus in castrated rats which had received testosterone seven days after tenotomy of the gastrocnemius was 25% as compared with muscles of castrated animals. The corresponding value in the plantaris muscle was 10%. 4. These results indicate that even calf muscles of the rat, namely the soleus and plantaris muscles, are significantly affected by testosterone under these conditions, although it is not, as yet, clear whether its action is direct or indirect."} {"id": "PMID:162622", "title": "The effect of splenectomy on bone marrow haematopoiesis in mice.", "content": "Splenectomy was performed in strain H mice. Erythrocyte macrocytosis and an increase in the reticulocyte, leucocyte and thrombocyte count were found in the peripheral blood of splenectomized animals; only the erythrocyte count fell in the first 3 weeks after splenectomy. Changes in the myelogram during the first weeks after splenectomy were characterized by an increase in the proportion of cells of the erythrocytic and lymphocytic series. The stem cell count in the bone marrow (determined after Till and McCulloch) was slightly elevated on the 8th day after splenectomy, but in subsequent weeks was rather lower than the control group values. Whatever the post-splenectomy interval at which bone marrow was taken from splenectomized mice, there was no significant difference in the transplantation effect of bone marrow cells on white and thrombocyte haematopoiesis. Bone marrow transplantation was found have a stimulant effect only on the reticulocyte count and the sooner bone marrow was collected after splenectomy, the more pronounced the effect. Changes in the myelogram and splenogram of irradiated mice to which the bone marrow cells of splenectomized mice had been transplanted were relatively small.", "contents": "The effect of splenectomy on bone marrow haematopoiesis in mice. Splenectomy was performed in strain H mice. Erythrocyte macrocytosis and an increase in the reticulocyte, leucocyte and thrombocyte count were found in the peripheral blood of splenectomized animals; only the erythrocyte count fell in the first 3 weeks after splenectomy. Changes in the myelogram during the first weeks after splenectomy were characterized by an increase in the proportion of cells of the erythrocytic and lymphocytic series. The stem cell count in the bone marrow (determined after Till and McCulloch) was slightly elevated on the 8th day after splenectomy, but in subsequent weeks was rather lower than the control group values. Whatever the post-splenectomy interval at which bone marrow was taken from splenectomized mice, there was no significant difference in the transplantation effect of bone marrow cells on white and thrombocyte haematopoiesis. Bone marrow transplantation was found have a stimulant effect only on the reticulocyte count and the sooner bone marrow was collected after splenectomy, the more pronounced the effect. Changes in the myelogram and splenogram of irradiated mice to which the bone marrow cells of splenectomized mice had been transplanted were relatively small."} {"id": "PMID:162624", "title": "[Biochemical findings in proteincomposition of secretions of human malignant parotid tumours, chronic parotitis and sialadenoses (author's transl)].", "content": "In comparison to former investigations in pleomorphic adenoms and Wharthin tumours in the present paper secretion of IgA, lysozyme in correlation to flowrate and total secretion in glands with malignant tumours, inflammations and Sialadenosis were estimated. Thereby 12 patients with malignomas of the parotid gland, 11 patients with chronic parotitis and 12 with sialadenoses were examined. The following results were found: 1. The concentration of protein, IgA and Lysozym is significantly higher than in normal glands and in glands with pleomorphic adenomas and Wharthin tumours. 2. Differentialdiagnosis of Sialadenitis and Sialadenosis of parotid glands is possible by estimating the examined parameters. Thereby in glands with sialadenosis flowrate is higher than in normal glands, and significant lower in glands with sialadenitis. Moreover concentrations of IgA and Lysozyme and protein in glands with sialadenitis are evaluated.", "contents": "[Biochemical findings in proteincomposition of secretions of human malignant parotid tumours, chronic parotitis and sialadenoses (author's transl)]. In comparison to former investigations in pleomorphic adenoms and Wharthin tumours in the present paper secretion of IgA, lysozyme in correlation to flowrate and total secretion in glands with malignant tumours, inflammations and Sialadenosis were estimated. Thereby 12 patients with malignomas of the parotid gland, 11 patients with chronic parotitis and 12 with sialadenoses were examined. The following results were found: 1. The concentration of protein, IgA and Lysozym is significantly higher than in normal glands and in glands with pleomorphic adenomas and Wharthin tumours. 2. Differentialdiagnosis of Sialadenitis and Sialadenosis of parotid glands is possible by estimating the examined parameters. Thereby in glands with sialadenosis flowrate is higher than in normal glands, and significant lower in glands with sialadenitis. Moreover concentrations of IgA and Lysozyme and protein in glands with sialadenitis are evaluated."} {"id": "PMID:162627", "title": "Effect of hydratation on renal water and sodium excretion in patients with renal arterial stenosis (S) and essential hypertension (EH).", "content": "Water and electrolyte excretion after a large water load and a small Na load was studied in a group of healthy volunteers (C) and in patients with renal arterial stenosis (S) and essential hypertension (EH). It was found that both groups of hypertensive patients reacted to this stimulus by higher Na, Cl, Ca and Mg excretion tan group C. In the two hypertension groups, cumulative Na excretion was comparable in size, but cumulative water excretion was significantly greater in group EH than in group S. The results indicate that these differences can be attributed to different localization of reduced Na reabsorption in the nephron. Signs of a decrease in Na resorption were found in the distal part of the nephron in both hypertension groups, but in the EH group they were also found in the proximal part.", "contents": "Effect of hydratation on renal water and sodium excretion in patients with renal arterial stenosis (S) and essential hypertension (EH). Water and electrolyte excretion after a large water load and a small Na load was studied in a group of healthy volunteers (C) and in patients with renal arterial stenosis (S) and essential hypertension (EH). It was found that both groups of hypertensive patients reacted to this stimulus by higher Na, Cl, Ca and Mg excretion tan group C. In the two hypertension groups, cumulative Na excretion was comparable in size, but cumulative water excretion was significantly greater in group EH than in group S. The results indicate that these differences can be attributed to different localization of reduced Na reabsorption in the nephron. Signs of a decrease in Na resorption were found in the distal part of the nephron in both hypertension groups, but in the EH group they were also found in the proximal part."} {"id": "PMID:162628", "title": "[Sudden deafness in connection with mumps (author's transl)].", "content": "The authors report three cases of sudden deafness due to mumps. On the first and second case (children) the deafness was severe perceptive and bilateral; in the first case the perceptive deafness occurred on the eight day while in the second case the forteenth day from the onset of mumps. On the third case (male adult) the deafness was unilateral, sudden with degeneration of vestibular, which occurred during virumia of mumps. The characteristic of this case is that the total deafness of right ear is associated with right parotitis and right orchitis. According to bibliography the pathogenesis, the time of deafness, appearance and the degree of hearing loss are discussed.", "contents": "[Sudden deafness in connection with mumps (author's transl)]. The authors report three cases of sudden deafness due to mumps. On the first and second case (children) the deafness was severe perceptive and bilateral; in the first case the perceptive deafness occurred on the eight day while in the second case the forteenth day from the onset of mumps. On the third case (male adult) the deafness was unilateral, sudden with degeneration of vestibular, which occurred during virumia of mumps. The characteristic of this case is that the total deafness of right ear is associated with right parotitis and right orchitis. According to bibliography the pathogenesis, the time of deafness, appearance and the degree of hearing loss are discussed."} {"id": "PMID:162629", "title": "[Laryngocele and Carcinoma (author's transl)].", "content": "A case of laryngocele and carcinoma is presented. A carcinoma of the right ventricular pouch has developed after a long period of chronic inflammation of the larynx. A big internal ipsilateral laryngocele was found in the larynx specimen. The incidence of laryngocele and carcinoma is demonstrated by available literature and by own investigations. Problems concerning the difficulty of diagnosis and pathogenesis are discussed.", "contents": "[Laryngocele and Carcinoma (author's transl)]. A case of laryngocele and carcinoma is presented. A carcinoma of the right ventricular pouch has developed after a long period of chronic inflammation of the larynx. A big internal ipsilateral laryngocele was found in the larynx specimen. The incidence of laryngocele and carcinoma is demonstrated by available literature and by own investigations. Problems concerning the difficulty of diagnosis and pathogenesis are discussed."} {"id": "PMID:162631", "title": "Utilization of 15N-urea administered into the sheep small intestine.", "content": "The retention and excretion of intrajejunally administered 15N-urea was studied in four experiments on two sheep with a permanently fistulated small intestine. In the first 7 days after the administration of 2 g 15N-urea, 18.26% was excreted in the faeces and 19% in the urine; 62.74% was retained in the organism. Urinary excretion took place mainly on the first day and from the 3rd to the 7th day no 15N was present in the urine. The rate of 15N excretion in the faeces was roughly the same for the first 4 days and then fell; on the 7th day there was no 15N in the faeces. The proportion of 15N-urea retained in the organism and excreted in the urine was 81% showing that urea in the ruminant gastrointestinal tract is largely linked up into metabolic circulation as part of the general exchange of nitrogenous compounds.", "contents": "Utilization of 15N-urea administered into the sheep small intestine. The retention and excretion of intrajejunally administered 15N-urea was studied in four experiments on two sheep with a permanently fistulated small intestine. In the first 7 days after the administration of 2 g 15N-urea, 18.26% was excreted in the faeces and 19% in the urine; 62.74% was retained in the organism. Urinary excretion took place mainly on the first day and from the 3rd to the 7th day no 15N was present in the urine. The rate of 15N excretion in the faeces was roughly the same for the first 4 days and then fell; on the 7th day there was no 15N in the faeces. The proportion of 15N-urea retained in the organism and excreted in the urine was 81% showing that urea in the ruminant gastrointestinal tract is largely linked up into metabolic circulation as part of the general exchange of nitrogenous compounds."} {"id": "PMID:162632", "title": "Age-related differences in the effect of glucagon on metabolism in rat liver.", "content": "The authors found differences in the metabolic response of 10- and 120-day-old rats to glucagon. In 10-day-old young, the administration of glucagon was followed in 5 min by an abrupt small increase in the blood sugar level, which continued to rise and attained the maximum 2 hours after the injection of glucagon. In adult rats there was an abrupt large increase in the blood sugar level in the first minutes after administering glucagon; after that the blood sugar level fell, but remained significantly higher than in the controls. In a series of experiments on the isolated perfused liver, no differences were found in glucose and protein release from the liver into the perfusion medium, but the protein concentration in the liver of the younger rats fell. The results show that the liver of young rats, after the injection of glucagon, draws on its own protein resources for the substrates needed for gluconeogenesis.", "contents": "Age-related differences in the effect of glucagon on metabolism in rat liver. The authors found differences in the metabolic response of 10- and 120-day-old rats to glucagon. In 10-day-old young, the administration of glucagon was followed in 5 min by an abrupt small increase in the blood sugar level, which continued to rise and attained the maximum 2 hours after the injection of glucagon. In adult rats there was an abrupt large increase in the blood sugar level in the first minutes after administering glucagon; after that the blood sugar level fell, but remained significantly higher than in the controls. In a series of experiments on the isolated perfused liver, no differences were found in glucose and protein release from the liver into the perfusion medium, but the protein concentration in the liver of the younger rats fell. The results show that the liver of young rats, after the injection of glucagon, draws on its own protein resources for the substrates needed for gluconeogenesis."} {"id": "PMID:162669", "title": "Diclofenac sodium (Voltaren): results of a multi-centre comparative trial in adult-onset rheumatoid arthritis.", "content": "A short-term trial has been performed under double-blind conditions in 50 adult patients with rheumatoid arthritis to compare diclofenac sodium (Voltaren) with both indomethacin and placebo for efficacy and tolerability. The duration of the trial was two weeks and was a between-patient comparison of 25 mg t.i.d. diclofenac sodium, 25 mg t.i.d. indomethacin or placebo using a double-dummy technique. Forty-eight patients completed the trial. In the majority of parameters examined, diclofenac sodium was superior to placebo and indomethacin in therapeutic effect. One patient was withdrawn from the trial because of intolerance to indomethacin and one other because of severe joint pain under indomethacin therapy. Neither active compound caused clinically significant changes in blood picture or urine analysis.", "contents": "Diclofenac sodium (Voltaren): results of a multi-centre comparative trial in adult-onset rheumatoid arthritis. A short-term trial has been performed under double-blind conditions in 50 adult patients with rheumatoid arthritis to compare diclofenac sodium (Voltaren) with both indomethacin and placebo for efficacy and tolerability. The duration of the trial was two weeks and was a between-patient comparison of 25 mg t.i.d. diclofenac sodium, 25 mg t.i.d. indomethacin or placebo using a double-dummy technique. Forty-eight patients completed the trial. In the majority of parameters examined, diclofenac sodium was superior to placebo and indomethacin in therapeutic effect. One patient was withdrawn from the trial because of intolerance to indomethacin and one other because of severe joint pain under indomethacin therapy. Neither active compound caused clinically significant changes in blood picture or urine analysis."} {"id": "PMID:162670", "title": "Long-term tolerability study of Voltaren.", "content": "Clinical and laboratory examinations were conducted in order to assess the long-term tolerability of Voltaren, a new anti-inflammatory and analgesic agent. Pre-treatment, repeated on-treatment and after-treatment investigations of haemoglobin, erythrocyte count, total and differential leucocyte count, platelet count, SGOT, SGPT, alkaline phosphatase, total serum proteins and urinary protein and sugar were conducted in 13 patients. The period of treatment with Voltaren was 110 to 559 days. In all these tests, there were no unwanted effects attributable to long-term treatment with Voltaren. Our study would indicate that Voltaren is a safe drug which has no effect on the organs of haemopoiesis, nor on hepatic or renal function, even in long-term therapy. Therefore, Voltaren can be used as an anti-inflammatory and analgesic agent not only in short-term therapy but also in the long-term treatment of chronic diseases.", "contents": "Long-term tolerability study of Voltaren. Clinical and laboratory examinations were conducted in order to assess the long-term tolerability of Voltaren, a new anti-inflammatory and analgesic agent. Pre-treatment, repeated on-treatment and after-treatment investigations of haemoglobin, erythrocyte count, total and differential leucocyte count, platelet count, SGOT, SGPT, alkaline phosphatase, total serum proteins and urinary protein and sugar were conducted in 13 patients. The period of treatment with Voltaren was 110 to 559 days. In all these tests, there were no unwanted effects attributable to long-term treatment with Voltaren. Our study would indicate that Voltaren is a safe drug which has no effect on the organs of haemopoiesis, nor on hepatic or renal function, even in long-term therapy. Therefore, Voltaren can be used as an anti-inflammatory and analgesic agent not only in short-term therapy but also in the long-term treatment of chronic diseases."} {"id": "PMID:162671", "title": "A double-blind clinical trial to determine if an interaction exists between diclofenac sodium and the oral anticoagulant acenocoumarol (nicoumalone).", "content": "A double-blind crossover trial between diclofenac sodium and placebo was carried out in 32 hospitalized patients who were thought to be stabilized on concurrent anticoagulant therapy with acenocoumarol. The object of the trial was to investigate any possible interaction between diclofenac and anticoagulant by monitoring prothrombin times daily through the four week period. No statistically significant difference between placebo and diclofenac could be shown and some problems of accurately monitoring prothrombin times are discussed.", "contents": "A double-blind clinical trial to determine if an interaction exists between diclofenac sodium and the oral anticoagulant acenocoumarol (nicoumalone). A double-blind crossover trial between diclofenac sodium and placebo was carried out in 32 hospitalized patients who were thought to be stabilized on concurrent anticoagulant therapy with acenocoumarol. The object of the trial was to investigate any possible interaction between diclofenac and anticoagulant by monitoring prothrombin times daily through the four week period. No statistically significant difference between placebo and diclofenac could be shown and some problems of accurately monitoring prothrombin times are discussed."} {"id": "PMID:162672", "title": "A long-term double-blind clinical trial of ibuprofen and indomethacin in rheumatoid arthritis.", "content": "Two-hundred and eighteen individuals with rheumatoid arthritis were randomly assigned to six months treatment with ibuprofen (900-1800 mg/day) or indomethacin (75-150 mg/day). The drugs were equally effective in the treatment of rheumatoid arthritis while the incidence of indomethacin side-effects was 1.5 times greater than the incidence of ibuprofen side-effects.", "contents": "A long-term double-blind clinical trial of ibuprofen and indomethacin in rheumatoid arthritis. Two-hundred and eighteen individuals with rheumatoid arthritis were randomly assigned to six months treatment with ibuprofen (900-1800 mg/day) or indomethacin (75-150 mg/day). The drugs were equally effective in the treatment of rheumatoid arthritis while the incidence of indomethacin side-effects was 1.5 times greater than the incidence of ibuprofen side-effects."} {"id": "PMID:162673", "title": "Studies on Ponstan (mefenamic acid): I. Gastro-intestinal blood loss; II. Absorbtion and excretion of a new formulation.", "content": "Using improved techniques in a study of faecal blood loss no significant change over control level occurred during administration of mefenamic acid 500 mg t.i.d. for six days. This lack of gastro-intestinal bleeding is at variance with earlier findings for this compound. Studies of two mefenamic acid formulations (250 mg capsule and 500 mg filmseal tablet) showed no significant difference in area under blood level curves or in urinary output data, indicating equivalent total absorption. The 500 mg film-coated tablet gave significantly higher serum levels at 0.5 hours, whereas the 250 mg capsule gave significantly higher serum levels at 6 and 8 hours.", "contents": "Studies on Ponstan (mefenamic acid): I. Gastro-intestinal blood loss; II. Absorbtion and excretion of a new formulation. Using improved techniques in a study of faecal blood loss no significant change over control level occurred during administration of mefenamic acid 500 mg t.i.d. for six days. This lack of gastro-intestinal bleeding is at variance with earlier findings for this compound. Studies of two mefenamic acid formulations (250 mg capsule and 500 mg filmseal tablet) showed no significant difference in area under blood level curves or in urinary output data, indicating equivalent total absorption. The 500 mg film-coated tablet gave significantly higher serum levels at 0.5 hours, whereas the 250 mg capsule gave significantly higher serum levels at 6 and 8 hours."} {"id": "PMID:162674", "title": "Clinical study on the efficacy of O-(beta-hydroxyethyl)rutoside (HR) in varicosis of pregnancy.", "content": "In a double-blind trial involving 69 patients, the effect of O-(beta-hydroxyethyl) rutoside (HR)* in the treatment of varicosis of pregnancy has been investigated. The number of patients subjectively improving in the active drug group was significantly greater than in the placebo group; patients receiving HR also showed a small but significant decrease in leg circumference. Throughout the eight-week period of the trial, there were only minimal side-effects and healthy babies were delivered with good Apgar-scores.", "contents": "Clinical study on the efficacy of O-(beta-hydroxyethyl)rutoside (HR) in varicosis of pregnancy. In a double-blind trial involving 69 patients, the effect of O-(beta-hydroxyethyl) rutoside (HR)* in the treatment of varicosis of pregnancy has been investigated. The number of patients subjectively improving in the active drug group was significantly greater than in the placebo group; patients receiving HR also showed a small but significant decrease in leg circumference. Throughout the eight-week period of the trial, there were only minimal side-effects and healthy babies were delivered with good Apgar-scores."} {"id": "PMID:162675", "title": "Isoxsuprine in primary dysmenorrhoea. Its effectiveness in premenstrual tension.", "content": "The drug combination including isoxsuprine 10 mg, acetaminophen 250 mg and caffeine 30 mg was administered to 80 patients divided into two groups, 40 with premenstrual tension and 40 with clinically diagnosed primary dysmenorrhoea. The study was carried out by the double-blind method and the patients were distributed at random. The results obtained show an excellent or very good response in 95% of cases of premenstrual tension and in 92.5% of cases of dysmenorrhoea. When the overall effectiveness of the compound in both conditions is considered, we find it to be 93.75%. A general discussion of the findings is presented in relation to age, civil status, time of appearance of dysmenorrhoea, nature of pain, accompanying symptoms, previous treatment, other non-drug therapies, results obtained, time within which symptoms were alleviated, total dose of the drug and side-effects. It is concluded that the orally-administered therapeutic combination is effective in both dysmenorrhoea and premenstrual tension.", "contents": "Isoxsuprine in primary dysmenorrhoea. Its effectiveness in premenstrual tension. The drug combination including isoxsuprine 10 mg, acetaminophen 250 mg and caffeine 30 mg was administered to 80 patients divided into two groups, 40 with premenstrual tension and 40 with clinically diagnosed primary dysmenorrhoea. The study was carried out by the double-blind method and the patients were distributed at random. The results obtained show an excellent or very good response in 95% of cases of premenstrual tension and in 92.5% of cases of dysmenorrhoea. When the overall effectiveness of the compound in both conditions is considered, we find it to be 93.75%. A general discussion of the findings is presented in relation to age, civil status, time of appearance of dysmenorrhoea, nature of pain, accompanying symptoms, previous treatment, other non-drug therapies, results obtained, time within which symptoms were alleviated, total dose of the drug and side-effects. It is concluded that the orally-administered therapeutic combination is effective in both dysmenorrhoea and premenstrual tension."} {"id": "PMID:162676", "title": "A comparison of mazindol (Teronac) with diethylpropion in the treatment of exogenous obesity.", "content": "Fifty obese patients were entered into a 12-week parallel group study of mazindol with diethylpropion in a general practice group. Both drugs produced weight loss, but patients on mazindol lost 19.9 lbs in 12 weeks, while those on diethylpropion lost 11.6 lbs, a statistically significant difference (p less than 0.01). At each visit during the trial, patients had lost more weight with mazindol, but this was only significant statistically in the period 8-12 weeks (p less than 0.01). Patients developed tolerance to the effect of diethylpropion in the last period (8-12 weeks) but this was not evident in those patients taking mazindol. The number of side-effects was less in the mazindol group and mainly of an adrenergic, peripheral type, while those in the diethylpropion group are mainly of the central stimulant type.", "contents": "A comparison of mazindol (Teronac) with diethylpropion in the treatment of exogenous obesity. Fifty obese patients were entered into a 12-week parallel group study of mazindol with diethylpropion in a general practice group. Both drugs produced weight loss, but patients on mazindol lost 19.9 lbs in 12 weeks, while those on diethylpropion lost 11.6 lbs, a statistically significant difference (p less than 0.01). At each visit during the trial, patients had lost more weight with mazindol, but this was only significant statistically in the period 8-12 weeks (p less than 0.01). Patients developed tolerance to the effect of diethylpropion in the last period (8-12 weeks) but this was not evident in those patients taking mazindol. The number of side-effects was less in the mazindol group and mainly of an adrenergic, peripheral type, while those in the diethylpropion group are mainly of the central stimulant type."} {"id": "PMID:162677", "title": "A placebo controlled trial of viloxazine with and without tranquillizers in depressive illness.", "content": "Two double-blind four-way crossover studies are reported, comparing the antidepressant effect of 14-day courses of: viloxazine, viloxazine with a tranquillizer either perphenazine or diazepam or tranquillizer alone, against a placebo. In one study the antidepressant effect of viloxazine at a dose of 150 mg daily was statistically greater than that of placebo, whilst in the second study viloxazine was statistically superior to diazepam (15 mg daily). In depressed patients with a clear anxiety component, viloxazine alone seemed preferable to a combination with a tranquillizer as such a combination did not produce an enhanced clinical effect and the incidence of side-effects was possibly increased. Viloxazine was generally well tolerated and side-effects, when they occurred, were generally a mild upper gastro-intestinal disturbance.", "contents": "A placebo controlled trial of viloxazine with and without tranquillizers in depressive illness. Two double-blind four-way crossover studies are reported, comparing the antidepressant effect of 14-day courses of: viloxazine, viloxazine with a tranquillizer either perphenazine or diazepam or tranquillizer alone, against a placebo. In one study the antidepressant effect of viloxazine at a dose of 150 mg daily was statistically greater than that of placebo, whilst in the second study viloxazine was statistically superior to diazepam (15 mg daily). In depressed patients with a clear anxiety component, viloxazine alone seemed preferable to a combination with a tranquillizer as such a combination did not produce an enhanced clinical effect and the incidence of side-effects was possibly increased. Viloxazine was generally well tolerated and side-effects, when they occurred, were generally a mild upper gastro-intestinal disturbance."} {"id": "PMID:162678", "title": "Clinical experience with Ro 5-3350 (bromazepam).", "content": "A pilot study using Ro 5-3350 was followed by a double-blind trial comparing Ro 5-3350 and chlordiazepoxide in a total of 25 patients who were either hospital in-patients or previous in-patients attending an out-patients follow-up clinic. The patients all had a long history of obsessive-compulsive or phobic symptoms. The visual analogue scale, the Taylor Manifest Anxiety Scale and clinical ratings were used to measure the response to treatment. In all three rating methods used, those patients who had received Ro 5-3350, chlordiazepoxide and then Ro 5-3350 in that order, consistently favoured Ro 5-3350. When the clinical ratings were examined by diagnostic groups, it was found that the phobic patients all gave favourable responses to Ro 5-3350. Two of the six patients with severe anxiety or agoraphobic states who had been treated with Ro 5-3350 over periods ranging from three to five years received the medication during the whole term of pregnancy and they were delivered of full-term normal babies. The results suggest that Ro 5-3350 (bromazepam) is a potent anxiolytic most likely to be effective in the relief of visceral manifestations of anxiety. The incidence of side-effects was low and there were no toxic effects reported.", "contents": "Clinical experience with Ro 5-3350 (bromazepam). A pilot study using Ro 5-3350 was followed by a double-blind trial comparing Ro 5-3350 and chlordiazepoxide in a total of 25 patients who were either hospital in-patients or previous in-patients attending an out-patients follow-up clinic. The patients all had a long history of obsessive-compulsive or phobic symptoms. The visual analogue scale, the Taylor Manifest Anxiety Scale and clinical ratings were used to measure the response to treatment. In all three rating methods used, those patients who had received Ro 5-3350, chlordiazepoxide and then Ro 5-3350 in that order, consistently favoured Ro 5-3350. When the clinical ratings were examined by diagnostic groups, it was found that the phobic patients all gave favourable responses to Ro 5-3350. Two of the six patients with severe anxiety or agoraphobic states who had been treated with Ro 5-3350 over periods ranging from three to five years received the medication during the whole term of pregnancy and they were delivered of full-term normal babies. The results suggest that Ro 5-3350 (bromazepam) is a potent anxiolytic most likely to be effective in the relief of visceral manifestations of anxiety. The incidence of side-effects was low and there were no toxic effects reported."} {"id": "PMID:162743", "title": "Methaqualone discrimination in gerbils: interactions with bemegride and imidazoline (DH-524).", "content": "Gerbils were trained in a T-maze to discriminate methaqualone (MTQ), either 16 mg/kg, 12 mg/kg, 8 mg/kg, or 4 mg/kg, from the no drug condition. Discrimination was proportional to dose, MTQ 16 mg/kg vs. no drug being the most rapidly discriminable condition. Challenge of MTQ discrimination with bemegride and imidazoline showed that bemegride, but not imidazoline reversed the MTQ discrimination. The median effective dose of bemegride was related to the amount of MTQ used (16-8 mg/kg).", "contents": "Methaqualone discrimination in gerbils: interactions with bemegride and imidazoline (DH-524). Gerbils were trained in a T-maze to discriminate methaqualone (MTQ), either 16 mg/kg, 12 mg/kg, 8 mg/kg, or 4 mg/kg, from the no drug condition. Discrimination was proportional to dose, MTQ 16 mg/kg vs. no drug being the most rapidly discriminable condition. Challenge of MTQ discrimination with bemegride and imidazoline showed that bemegride, but not imidazoline reversed the MTQ discrimination. The median effective dose of bemegride was related to the amount of MTQ used (16-8 mg/kg)."} {"id": "PMID:162748", "title": "[Participation of interoceptive afferent excitations in sensory integration processes of cat visual cortex neurons].", "content": "In experiments on cats immobilized with diplacine it is shown that stimulation of the vagal and splanchnic nerves exerts a substantial influence on the neuronal background activity of field 17 in the brain cortex. Neuronal responses as prolonged tonic changes in impulse frequency were seen more often. Complex phasic neuronal responses with steady inhibitory periods and periods of activation appeared more rarely. The development of phasic reactions could begin both with activation and initial inhibition of the activity. Predominantly excitatory responses resulted from the splanchnic nerve stimulation. They could be also seen during somatic stimulations. The degree of neuronal involvement into the responses and their intensity increased by trains of stimuli. Visceral and somatic influences on the visual cortical neurons are shown to be mediated by the lateral hypothalamus and midbrain reticular formation.", "contents": "[Participation of interoceptive afferent excitations in sensory integration processes of cat visual cortex neurons]. In experiments on cats immobilized with diplacine it is shown that stimulation of the vagal and splanchnic nerves exerts a substantial influence on the neuronal background activity of field 17 in the brain cortex. Neuronal responses as prolonged tonic changes in impulse frequency were seen more often. Complex phasic neuronal responses with steady inhibitory periods and periods of activation appeared more rarely. The development of phasic reactions could begin both with activation and initial inhibition of the activity. Predominantly excitatory responses resulted from the splanchnic nerve stimulation. They could be also seen during somatic stimulations. The degree of neuronal involvement into the responses and their intensity increased by trains of stimuli. Visceral and somatic influences on the visual cortical neurons are shown to be mediated by the lateral hypothalamus and midbrain reticular formation."} {"id": "PMID:162746", "title": "Algorithm for management of pulmonary complications in burn patients.", "content": "An algorithm for management of pulmonary complications in burn patients on the same basis as in patients with adult respiratory distress syndrome is outline. Pao2 of less than 60 torr (F(I)O2 0.21-0.4, PaCO2 over 40 torr, pH less than 7.35, respiratory rate over 40/min, and clinical evidence of compromised upper airway were the indications for initation of aggressive intensive respiratory care. This consisted of nasotracheal intubation, arterial cannulation, pulmonary artery catheterization, and establishment of mechanical ventilation. The algorithm further defines the subsequent management of these patients as far as need for continued mechanical ventilation, fluid and electrolyte balance, hemodynamic stability, and renal function.", "contents": "Algorithm for management of pulmonary complications in burn patients. An algorithm for management of pulmonary complications in burn patients on the same basis as in patients with adult respiratory distress syndrome is outline. Pao2 of less than 60 torr (F(I)O2 0.21-0.4, PaCO2 over 40 torr, pH less than 7.35, respiratory rate over 40/min, and clinical evidence of compromised upper airway were the indications for initation of aggressive intensive respiratory care. This consisted of nasotracheal intubation, arterial cannulation, pulmonary artery catheterization, and establishment of mechanical ventilation. The algorithm further defines the subsequent management of these patients as far as need for continued mechanical ventilation, fluid and electrolyte balance, hemodynamic stability, and renal function."} {"id": "PMID:162750", "title": "[Pathogenicity of atypical mycobacteria].", "content": "Human diseases caused by atypical mycobacteria are reviewed. Pulmonary illness and childrens' lymphadenitis are the commonest, but cutaneous, disseminated, bony, articular, renal and meningeal diseases are also produced by atypical mycobacteria. Disseminated infections are often manifested by fever, hepato-splenomegaly and hematologic changes. Most diagnosis are made by sputum and gastric-juice cultures, bonemarrow and liver biopsies. Disseminated diseases are often fatal but may be cured with medical treatment. In general, atypical mycobacterial diseases are quite similar to tuberculous diseases in different organs. A unique isolation of atypical mycobacteria is not diagnostic \"by it self\", and other conditions are required. Diagnostic criteria and treatment are discussed.", "contents": "[Pathogenicity of atypical mycobacteria]. Human diseases caused by atypical mycobacteria are reviewed. Pulmonary illness and childrens' lymphadenitis are the commonest, but cutaneous, disseminated, bony, articular, renal and meningeal diseases are also produced by atypical mycobacteria. Disseminated infections are often manifested by fever, hepato-splenomegaly and hematologic changes. Most diagnosis are made by sputum and gastric-juice cultures, bonemarrow and liver biopsies. Disseminated diseases are often fatal but may be cured with medical treatment. In general, atypical mycobacterial diseases are quite similar to tuberculous diseases in different organs. A unique isolation of atypical mycobacteria is not diagnostic \"by it self\", and other conditions are required. Diagnostic criteria and treatment are discussed."} {"id": "PMID:162751", "title": "[Stimulation of replanted extremity muscles and its effect on energy processes].", "content": "Medicamental stimulation has a definite positive effect on metabolism of macroergic compounds in the muscles of the replanted and contralateral extremeties. Application of medicamental stimulation reduced the time for the muscle reparation, increased considerably the level of creatine-phosphoric acid and ATP both in the replanted and intact extremeties as well as restored the succinate dehydrogenase activity. 4-Methyluracil applied in combination with vitamins proved to be the most effective preparation under conditions of the experiment.", "contents": "[Stimulation of replanted extremity muscles and its effect on energy processes]. Medicamental stimulation has a definite positive effect on metabolism of macroergic compounds in the muscles of the replanted and contralateral extremeties. Application of medicamental stimulation reduced the time for the muscle reparation, increased considerably the level of creatine-phosphoric acid and ATP both in the replanted and intact extremeties as well as restored the succinate dehydrogenase activity. 4-Methyluracil applied in combination with vitamins proved to be the most effective preparation under conditions of the experiment."} {"id": "PMID:162761", "title": "The aetiology of acute pancreatitis.", "content": "The most common aetiological factors of acute pancreatitis in an unselected group of 215 consecutive surgical patients were biliary tract disease (40.0%), alcoholism (20.0%) and gastroduodenal ulcer (4.2%). In women, biliary tract disease was by far the most common cause (61.3%), but in men considerably high frequencies of alcoholism (48.3%) and gastroduodenal ulcer (15.7%) were noted as at least one possible aetiological factor. This deserves a special notation when contemplating prophylactic measures to prevent recurrences of acute pancreatitis.", "contents": "The aetiology of acute pancreatitis. The most common aetiological factors of acute pancreatitis in an unselected group of 215 consecutive surgical patients were biliary tract disease (40.0%), alcoholism (20.0%) and gastroduodenal ulcer (4.2%). In women, biliary tract disease was by far the most common cause (61.3%), but in men considerably high frequencies of alcoholism (48.3%) and gastroduodenal ulcer (15.7%) were noted as at least one possible aetiological factor. This deserves a special notation when contemplating prophylactic measures to prevent recurrences of acute pancreatitis."} {"id": "PMID:162762", "title": "Amniotic fluid removal prior to saline abortion.", "content": "To evaluate whether removal of the amniotic fluid prior to the instillation of 200 ml of 20% hypertonic saline has any effect on the success, speed, and safety of the abortion process, 192 patients at 15-20 weeks' gestation were aborted according to one of the following procedures: 1) instillation of 200 ml saline without removal of the amniotic fluid (92 subjects), 2) removal of 100 ml of amniotic fluid prior to saline instillation (46 subjects), and 3) removal of 150 ml of amniotic fluid prior saline instillation (54 subjects). The study indicated that there are no apparent advantages to the removal of the amniotic fluid prior to the instillation of 200 ml of hypertonic saline. The median times from instillation to abortion and rates of incomplete abortion were similar for the three groups of patients. Rates of specific complications, except for fever, were similar for the three groups.", "contents": "Amniotic fluid removal prior to saline abortion. To evaluate whether removal of the amniotic fluid prior to the instillation of 200 ml of 20% hypertonic saline has any effect on the success, speed, and safety of the abortion process, 192 patients at 15-20 weeks' gestation were aborted according to one of the following procedures: 1) instillation of 200 ml saline without removal of the amniotic fluid (92 subjects), 2) removal of 100 ml of amniotic fluid prior to saline instillation (46 subjects), and 3) removal of 150 ml of amniotic fluid prior saline instillation (54 subjects). The study indicated that there are no apparent advantages to the removal of the amniotic fluid prior to the instillation of 200 ml of hypertonic saline. The median times from instillation to abortion and rates of incomplete abortion were similar for the three groups of patients. Rates of specific complications, except for fever, were similar for the three groups."} {"id": "PMID:162769", "title": "Medulloblastoma. Treatment results.", "content": "A series of 44 patients with medulloblastoma is presented. The treatment was primary operation followed by irradiation of the entire CNS. The 3-year and 5-year survival rates for children and adults together were 36 and 33 per cent, respectively, and for children alone 37 amd 33 per cent, respectively. No certain difference in the prognosis for boys and girls was found.", "contents": "Medulloblastoma. Treatment results. A series of 44 patients with medulloblastoma is presented. The treatment was primary operation followed by irradiation of the entire CNS. The 3-year and 5-year survival rates for children and adults together were 36 and 33 per cent, respectively, and for children alone 37 amd 33 per cent, respectively. No certain difference in the prognosis for boys and girls was found."} {"id": "PMID:162770", "title": "High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation.", "content": "In a phase II investigation of high dose medroxyprogesterone treatment of advanced and previously with other methods heavily treated patient with mammary carcinoma, 7 of 25 patients had a partial remission with a median duration of 5 + months. In a further 7 patients the disease became stationary. As measured by Karnofsky's scale, a median improvement of 20 points was obtained in these 14 patients. In 4 of 15 patients who had not responded to Tamoxifen treatment, a partial remission occurred following MAP therapy. The patients tolerated MAP well.", "contents": "High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation. In a phase II investigation of high dose medroxyprogesterone treatment of advanced and previously with other methods heavily treated patient with mammary carcinoma, 7 of 25 patients had a partial remission with a median duration of 5 + months. In a further 7 patients the disease became stationary. As measured by Karnofsky's scale, a median improvement of 20 points was obtained in these 14 patients. In 4 of 15 patients who had not responded to Tamoxifen treatment, a partial remission occurred following MAP therapy. The patients tolerated MAP well."} {"id": "PMID:162771", "title": "Skin reactions in mouse by fractionated neutron irradiations with the same NSDn.", "content": "The results of three fractionations of neutron irradiation with the same NSDn were examined for skin reactions in mice. No significant differences were observed between these fractionations given two times a week (15 Gy/12 fractionations/39 days, 14.6 Gy/10 fractionations/32 days and 14.08 Gy/8 fractionations/25 days). The result suggests the value of a high dose per fraction given two times a week.", "contents": "Skin reactions in mouse by fractionated neutron irradiations with the same NSDn. The results of three fractionations of neutron irradiation with the same NSDn were examined for skin reactions in mice. No significant differences were observed between these fractionations given two times a week (15 Gy/12 fractionations/39 days, 14.6 Gy/10 fractionations/32 days and 14.08 Gy/8 fractionations/25 days). The result suggests the value of a high dose per fraction given two times a week."} {"id": "PMID:162772", "title": "Demographic investigation of mammary carcinoma in Northern Sweden.", "content": "The age standardized incidence rates for female breast carcinoma were calculated for the 3 northernmost counties in Sweden and their municipalities for the period 1959 to 1971. Large variations were found that could not be explained by random distribution. Lower incidences were encountered in the less urbanized municipalities in the western and northern parts. The largest relative difference between low-incidence and high-incidence municipalities concerned the post-menopausal period.", "contents": "Demographic investigation of mammary carcinoma in Northern Sweden. The age standardized incidence rates for female breast carcinoma were calculated for the 3 northernmost counties in Sweden and their municipalities for the period 1959 to 1971. Large variations were found that could not be explained by random distribution. Lower incidences were encountered in the less urbanized municipalities in the western and northern parts. The largest relative difference between low-incidence and high-incidence municipalities concerned the post-menopausal period."} {"id": "PMID:162774", "title": "Hemofiltration during extracorporeal circulation (ECC).", "content": "In cardiac surgery hemofiltration can be used: 1. to balance fluids during ECC, especially in long-term perfusion; 2. to carry out open heart procedures in patients with terminal renal insufficiency; 3. to treat acute hyperkalemia. The model of the 12.5 by 4.5 cm DIAFILTER TM and the model of operation are described. The compounds of the ultrafiltrate (UF) are identical with that of plasma water. Particles with a molecular weight of less than 50,000 can pass freely across the filtration membrane. The filtration capacity is 100 cc/min UF (Q blood: 300 cc/min, pressure across the membrane 600 mm Hg and hematokrit (Hkt) 25%). The technical details of operation are explained. Its general use as well as its simplicity is demonstrated in 10 patients.", "contents": "Hemofiltration during extracorporeal circulation (ECC). In cardiac surgery hemofiltration can be used: 1. to balance fluids during ECC, especially in long-term perfusion; 2. to carry out open heart procedures in patients with terminal renal insufficiency; 3. to treat acute hyperkalemia. The model of the 12.5 by 4.5 cm DIAFILTER TM and the model of operation are described. The compounds of the ultrafiltrate (UF) are identical with that of plasma water. Particles with a molecular weight of less than 50,000 can pass freely across the filtration membrane. The filtration capacity is 100 cc/min UF (Q blood: 300 cc/min, pressure across the membrane 600 mm Hg and hematokrit (Hkt) 25%). The technical details of operation are explained. Its general use as well as its simplicity is demonstrated in 10 patients."} {"id": "PMID:162776", "title": "Management of ascending suture line sepsis by excision on the ascending aorta and insertion of a left ventricular apex to aorta conduit.", "content": "A new technique used in the management of infection of an aortic suture line following aortic valve replacement and subsequent episodes of severe hemorrhage resulting from suture line disruption is described. In a planned, staged procedure, a left-ventricular-apex-to-aorta conduit was inserted followed by excision of the supracoronary aortic root and ascending aorta, incorporating all infected tissue. This technique demonstrates that near total excision of the ascending aorta is possible and coronary artery flow can be maintained with only a minimal supravalvular aortic chamber.", "contents": "Management of ascending suture line sepsis by excision on the ascending aorta and insertion of a left ventricular apex to aorta conduit. A new technique used in the management of infection of an aortic suture line following aortic valve replacement and subsequent episodes of severe hemorrhage resulting from suture line disruption is described. In a planned, staged procedure, a left-ventricular-apex-to-aorta conduit was inserted followed by excision of the supracoronary aortic root and ascending aorta, incorporating all infected tissue. This technique demonstrates that near total excision of the ascending aorta is possible and coronary artery flow can be maintained with only a minimal supravalvular aortic chamber."} {"id": "PMID:162779", "title": "Program evaluation of Texas mental health and mental retardation centers.", "content": "The diversity of programs offered by the 24 mental health and mental retardation centers in Texas required that program evaluation take a management-by-objectives approach, with each center examined as a unique system with its own goals, techniques, and activities. The approach required the centers to develop statements of management objectives, which they did with varying degrees of success. The evaluations were carried out by site-visit teams. The authors describe the evaluation process, the difficulties encountered, and some of the beneficial effects.", "contents": "Program evaluation of Texas mental health and mental retardation centers. The diversity of programs offered by the 24 mental health and mental retardation centers in Texas required that program evaluation take a management-by-objectives approach, with each center examined as a unique system with its own goals, techniques, and activities. The approach required the centers to develop statements of management objectives, which they did with varying degrees of success. The evaluations were carried out by site-visit teams. The authors describe the evaluation process, the difficulties encountered, and some of the beneficial effects."} {"id": "PMID:162782", "title": "Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect.", "content": "Cholesterol-rich membranes are the hallmark of \"spur\" red cells. Spur cells accumulate cholesterol from cholesterol-rich serum lipoproteins. Previous studies suggested that this added cholesterol is responsible for both the altered morphology and the destruction of spur cells. To examine this process in the absence of other serum factors, cholesterol-lecithin dispersions with varying amounts of unesterified cholesterol (C) relative to phospholipid (P) were prepared, and their influence on normal human red cells was studied. Cholesterol-rich lipid dispersions (C/P mole ration greater 1.0) transferred cholesterol to both red cell membranes and serum lipoproteins, and cholesterol-poor dispersions (C/P mole ration less 1.0) depleted red cells of cholesterol. Changes in membrane cholesterol paralleled changes in membrane surface area, as calculated from osmotic fragility, with a 0.22 percent variation in surface area per 1.0 percent variation in cholesterol content. Cold-induced compression of membrane surface area was increased in cholesterol-poor red cells (C/P equals 0.4), whereas the surface area of cholesterol-rich membranes (C/P equals 1.80) underwent no compression. Although the Na and K permeability of red cells severely depleted of cholesterol was increased, lesser degrees of depletion had no effect, and the permeability of cholesterol-rich cells was normal. However, increasing membrane cholesterol caused a progressive decrease in red cell deformability, as measured by filtration. Cholesterol-poor red cells were spherocytic in appearance and cholesterol-rich cells were broad and flat, indicative of their surface areas. In addition, cholesterol-rich cells had an irregular contour due to folding of the periphery of the cell. This shape abnormality was identical to that of both spur cells after splenectomy and normal red cells incubated in spur serum. Normalization of the C/P of spur serum by added phospholipid prevented the increase in membrane cholesterol and surface area and the transformation of cell shape. These studies establish that the cholesterol content of red cells is dependent on the C/P of their milieu, either lipoproteins or cholesterol-lecithin dispersions. Moreover, the surface area, deformability, and contour of cholesterol-rich red cells are a direct function of their increased membrane C/P. Although cholesterol-rich spur cells are further modified in the circulation of patients with spleens, this abnormality of the membrane lipid bilayer, induced by cholesterol-rich cholesterol-lecithin dispersions, represents the primary spur cell defect.", "contents": "Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect. Cholesterol-rich membranes are the hallmark of \"spur\" red cells. Spur cells accumulate cholesterol from cholesterol-rich serum lipoproteins. Previous studies suggested that this added cholesterol is responsible for both the altered morphology and the destruction of spur cells. To examine this process in the absence of other serum factors, cholesterol-lecithin dispersions with varying amounts of unesterified cholesterol (C) relative to phospholipid (P) were prepared, and their influence on normal human red cells was studied. Cholesterol-rich lipid dispersions (C/P mole ration greater 1.0) transferred cholesterol to both red cell membranes and serum lipoproteins, and cholesterol-poor dispersions (C/P mole ration less 1.0) depleted red cells of cholesterol. Changes in membrane cholesterol paralleled changes in membrane surface area, as calculated from osmotic fragility, with a 0.22 percent variation in surface area per 1.0 percent variation in cholesterol content. Cold-induced compression of membrane surface area was increased in cholesterol-poor red cells (C/P equals 0.4), whereas the surface area of cholesterol-rich membranes (C/P equals 1.80) underwent no compression. Although the Na and K permeability of red cells severely depleted of cholesterol was increased, lesser degrees of depletion had no effect, and the permeability of cholesterol-rich cells was normal. However, increasing membrane cholesterol caused a progressive decrease in red cell deformability, as measured by filtration. Cholesterol-poor red cells were spherocytic in appearance and cholesterol-rich cells were broad and flat, indicative of their surface areas. In addition, cholesterol-rich cells had an irregular contour due to folding of the periphery of the cell. This shape abnormality was identical to that of both spur cells after splenectomy and normal red cells incubated in spur serum. Normalization of the C/P of spur serum by added phospholipid prevented the increase in membrane cholesterol and surface area and the transformation of cell shape. These studies establish that the cholesterol content of red cells is dependent on the C/P of their milieu, either lipoproteins or cholesterol-lecithin dispersions. Moreover, the surface area, deformability, and contour of cholesterol-rich red cells are a direct function of their increased membrane C/P. Although cholesterol-rich spur cells are further modified in the circulation of patients with spleens, this abnormality of the membrane lipid bilayer, induced by cholesterol-rich cholesterol-lecithin dispersions, represents the primary spur cell defect."} {"id": "PMID:162783", "title": "Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action.", "content": "The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis.", "contents": "Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action. The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis."} {"id": "PMID:162784", "title": "In vitro binding of L-triiodothyronine to receptors in rat liver nuclei. Kinectics of binding, extraction properties, and lack of requirement for cytosol proteins.", "content": "Isolated hepatic nuclei from euthyroid rats were incubated with tracer (125I)L-triiodothyronine (T3) and increasing doses of nonradioactive T3 for 30 min at 37degrees C. The T3 bound specifically to nuclear sites increased with increasing T3 doses to a plateau, which represented the nuclear binding capacity, M. Addition of 1 mM KCN, NaF, dinitrophenol, oriodoacetate did not affect nuclear binding, indicating that active metabolism was not required. Kinetic studies showed that the nuclear sites were equilibrated with T3 within 30 min of incubation (one-half maximal binding at 3 min) and that the rate of release of T3 in vitro (0.058 min-1) was the same for endogenous T3 or for T3 bound to nuclei in vitro. Nuclear T3 resisted extraction with 0.14 M NaC1 buffered at pH 7.5, but both endogenous hormone and T3 bound in vitro were readily extracted by 0.4 M KC1 at pH 8.0. The elution profiles of endogenous and in vitro-bound T3 from Sephadex G-100 columns showed a common protein peak with a molecular weight of 60-65,000, assuming a globular protein. Scatchard analysis of in vitro displacement studies showed a single class of binding sites. Mean M equals 0.23 times 10-9 M or 0.85 ng T3 for nuclei isolated from 1 g of liver. Mean M closely corresponded to that anticipated from reported in vivo studies. The apparent association constant Ka for the nuclear sites, 5.55 times 108 M-1, was lower than in studies in vivo, probably attributable to the different ionic milieu of nuclei in the incubation buffer and in the intact cell. Thus, the identity of the nuclear T3 binding sites studied in vitro to those reported for endogenous hormone is demonstrated by similar binding capacities, release rates, analogue binding affinities (previously reported), and localization to chromatin nonhistone proteins of comparable molecular weight. The role of cytosol protein in nuclear binding was assessed by comparing binding parameters for extensively washed nuclei and nuclei incubated either with contaminating or added cytosol. No difference in Ka or M was found. Moreover, it was unlikely that specific cytosol proteins were already present in nuclei and functioned during incubation as a shuttle for T3, since Ka and M for nuclei obtained from athyreotic rats were similar to Ka and M for nuclei from euthyroid animals. Thus, an initial interaction between T3 and specific cytosol proteins does not appear to be a prerequisite for translocation of T3 to nuclear sites.", "contents": "In vitro binding of L-triiodothyronine to receptors in rat liver nuclei. Kinectics of binding, extraction properties, and lack of requirement for cytosol proteins. Isolated hepatic nuclei from euthyroid rats were incubated with tracer (125I)L-triiodothyronine (T3) and increasing doses of nonradioactive T3 for 30 min at 37degrees C. The T3 bound specifically to nuclear sites increased with increasing T3 doses to a plateau, which represented the nuclear binding capacity, M. Addition of 1 mM KCN, NaF, dinitrophenol, oriodoacetate did not affect nuclear binding, indicating that active metabolism was not required. Kinetic studies showed that the nuclear sites were equilibrated with T3 within 30 min of incubation (one-half maximal binding at 3 min) and that the rate of release of T3 in vitro (0.058 min-1) was the same for endogenous T3 or for T3 bound to nuclei in vitro. Nuclear T3 resisted extraction with 0.14 M NaC1 buffered at pH 7.5, but both endogenous hormone and T3 bound in vitro were readily extracted by 0.4 M KC1 at pH 8.0. The elution profiles of endogenous and in vitro-bound T3 from Sephadex G-100 columns showed a common protein peak with a molecular weight of 60-65,000, assuming a globular protein. Scatchard analysis of in vitro displacement studies showed a single class of binding sites. Mean M equals 0.23 times 10-9 M or 0.85 ng T3 for nuclei isolated from 1 g of liver. Mean M closely corresponded to that anticipated from reported in vivo studies. The apparent association constant Ka for the nuclear sites, 5.55 times 108 M-1, was lower than in studies in vivo, probably attributable to the different ionic milieu of nuclei in the incubation buffer and in the intact cell. Thus, the identity of the nuclear T3 binding sites studied in vitro to those reported for endogenous hormone is demonstrated by similar binding capacities, release rates, analogue binding affinities (previously reported), and localization to chromatin nonhistone proteins of comparable molecular weight. The role of cytosol protein in nuclear binding was assessed by comparing binding parameters for extensively washed nuclei and nuclei incubated either with contaminating or added cytosol. No difference in Ka or M was found. Moreover, it was unlikely that specific cytosol proteins were already present in nuclei and functioned during incubation as a shuttle for T3, since Ka and M for nuclei obtained from athyreotic rats were similar to Ka and M for nuclei from euthyroid animals. Thus, an initial interaction between T3 and specific cytosol proteins does not appear to be a prerequisite for translocation of T3 to nuclear sites."} {"id": "PMID:162785", "title": "Primary fibrinolysis after oral surgery.", "content": "A case report of a patient with primary fibrinolysis resulting in hemorrhage after an oral surgical procedure has been presented. A comparison was made between DIC and primary fibrinolysis in patients with carcinoma of the prostate gland; etiology, clinical findings, diagnosis, and treatment were discussed.", "contents": "Primary fibrinolysis after oral surgery. A case report of a patient with primary fibrinolysis resulting in hemorrhage after an oral surgical procedure has been presented. A comparison was made between DIC and primary fibrinolysis in patients with carcinoma of the prostate gland; etiology, clinical findings, diagnosis, and treatment were discussed."} {"id": "PMID:162787", "title": "Computerized axial tomography in syringomyelia.", "content": "The ACTA-scanner, a device for computerized axial tomography, permits cross-sectional radiographic study of the entire human body, including the spine. In the ACTA-scan, the spinal cord appears as a roundish formation surrounded by the less dense subarachnoidal cerebrospinal fluid. The spines of 18 patients with verified (nine cases) or suspected (nine cases) syringomyelia were studied by ACTA-scanning. In seven of the verified and in four of the nonverified cases, some evidence of cord cavitation was shown. The cystic part of a cervical-cord ependymoma was also demonstrated. ACTA-scanning is an easily performed, noninvasive, innocuous procedure. This technic, which complements other radiographic methods of evaluating the spinal cord, is particularly suitable for screening and follow-up study of patients with syringomyelia. The easily accomplished recognition of a possible associated hydrocephalus is an added advantage of ACTA-scanning.", "contents": "Computerized axial tomography in syringomyelia. The ACTA-scanner, a device for computerized axial tomography, permits cross-sectional radiographic study of the entire human body, including the spine. In the ACTA-scan, the spinal cord appears as a roundish formation surrounded by the less dense subarachnoidal cerebrospinal fluid. The spines of 18 patients with verified (nine cases) or suspected (nine cases) syringomyelia were studied by ACTA-scanning. In seven of the verified and in four of the nonverified cases, some evidence of cord cavitation was shown. The cystic part of a cervical-cord ependymoma was also demonstrated. ACTA-scanning is an easily performed, noninvasive, innocuous procedure. This technic, which complements other radiographic methods of evaluating the spinal cord, is particularly suitable for screening and follow-up study of patients with syringomyelia. The easily accomplished recognition of a possible associated hydrocephalus is an added advantage of ACTA-scanning."} {"id": "PMID:162790", "title": "Secretion granules of the rabbit parotid gland. Isolation, subfractionation, and characterization of the membrane and content subfractions.", "content": "A fraction of secretion granules has been isolated from rabbit parotid by a procedure which was found to be especially effective in reducing contamination resulting from aggregation and/or cosedimentation of granules with other cell particulates. The fraction, representing 15 percent (on the average) of the total tissue amylase activity, was homogeneous as judged by electron microscopy and contaminated to exceedingly low levels by other cellular organelles as judged by marker enzymatic and chemical assays. Lysis of the granules was achieved by their gradual exposure to hypotonic NaHCO3, containing 0.5 mM EDTA. The content and the membranes separated by centrifugation of the granule lysate were characterized primarily by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis which indicated that the content was composed of a limited number of molecular weight classes of polypeptides of which three bands (having approximate mol wt 58,000, 33, 000, and 12,000) could be considered major components. The gel profile of the membrane subfraction was characterized by 20-30 Coomassie brilliant blue-staining bands of which a single species of mol wt 40,000 was the conspicuous major polypeptide. Two types of experiments employing gel electrophoretic analysis were carried out for identifying and assessing the extent of residual secretory protein adsorbed to purified granule membranes: (a) examination of staining and radioactivity profiles after mixing of radioactive secretion granule extract with nonradioactively labeled granule membranes and (b) comparison of gel profiles of secretion granule extract and granule membranes with those of unlysed secretion granules and secretory protein dischraged from lobules in vitro or collected by cannulation of parotid ducts, the last two samples being considered physiologic secretory standards. The results indicated that the membranes were contaminated to a substantial degree by residual, poorly extractable secretory protein even though assays of membrane fractions for a typical secretory enzyme activity (amylase) indicated quite through separation of membranes and content. Hence, detailed examination of membrane subfractions for residual content species by gel electrophoresis points to the general unity and sensitivity of this technique as a means for accurately detecting a defined set of polypeptides occurring as contaminants in cellular fractions or organelle subfractions.", "contents": "Secretion granules of the rabbit parotid gland. Isolation, subfractionation, and characterization of the membrane and content subfractions. A fraction of secretion granules has been isolated from rabbit parotid by a procedure which was found to be especially effective in reducing contamination resulting from aggregation and/or cosedimentation of granules with other cell particulates. The fraction, representing 15 percent (on the average) of the total tissue amylase activity, was homogeneous as judged by electron microscopy and contaminated to exceedingly low levels by other cellular organelles as judged by marker enzymatic and chemical assays. Lysis of the granules was achieved by their gradual exposure to hypotonic NaHCO3, containing 0.5 mM EDTA. The content and the membranes separated by centrifugation of the granule lysate were characterized primarily by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis which indicated that the content was composed of a limited number of molecular weight classes of polypeptides of which three bands (having approximate mol wt 58,000, 33, 000, and 12,000) could be considered major components. The gel profile of the membrane subfraction was characterized by 20-30 Coomassie brilliant blue-staining bands of which a single species of mol wt 40,000 was the conspicuous major polypeptide. Two types of experiments employing gel electrophoretic analysis were carried out for identifying and assessing the extent of residual secretory protein adsorbed to purified granule membranes: (a) examination of staining and radioactivity profiles after mixing of radioactive secretion granule extract with nonradioactively labeled granule membranes and (b) comparison of gel profiles of secretion granule extract and granule membranes with those of unlysed secretion granules and secretory protein dischraged from lobules in vitro or collected by cannulation of parotid ducts, the last two samples being considered physiologic secretory standards. The results indicated that the membranes were contaminated to a substantial degree by residual, poorly extractable secretory protein even though assays of membrane fractions for a typical secretory enzyme activity (amylase) indicated quite through separation of membranes and content. Hence, detailed examination of membrane subfractions for residual content species by gel electrophoresis points to the general unity and sensitivity of this technique as a means for accurately detecting a defined set of polypeptides occurring as contaminants in cellular fractions or organelle subfractions."} {"id": "PMID:162791", "title": "Cell cycle and growth stage-dependent changes in the transport of nucleosides, hypoxanthine, choline, and deoxyglucose in cultured Novikoff rat hepatoma cells.", "content": "Populations of Novikoff rat hepatoma cells (subline N1S1-67) were monitored for the rates of transport of various substrates and for their incorporation into acid-insoluble material as a function of the age of cultures of randomly growing cells in suspension as well as during traverse of the cells through the cell cycle. Populations of cells were synchronized by a double hydroxyurea block or by successive treatment with hydroxyurea and Colcemid. Kinetic analyses showed that changes in transport rates related to the age of cultures or the cell cycle stage reflecte alterations in the V max of the transport processes, whereas the Km remained constant, indicating that changes in transport rates reflect alterations in the number of functional transport sites. The transport sites for uridine and 2-deoxy-D-glucose increased continuously during traverse of the cells through the cell cycle, whereas those for choline and hypoxanthine were formed early in the cell cycle. Increases in thymidine transport sites were confined to the S phase. Synchronized cells deprived of serum failed to exhibit normal increases in transport sites, although the cells divided normally at the end of the cell cycle. Arrest of the cells in mitosis by treatment with Colcemid prevented any further increases in transport rates. The formation of functional transport sites was also dependent on de novo synthesis of RNA and protein. Inhibition of DNA synthesis in early S phase inhibited the increase in thymidine transport rates which normally occurs during the S phase, but had no effect on the formation of the other transport systems. Transport rates also fluctuated markedly with the age of the cultures of randomly growing cells, reaching maximum levels in the mid-exponential phase of growth. The transport systems for thymidine and uridine were rapidly lost upon inhibition of protein and RNA synthesis, and thus seem to be metabolically unstable, whereas the transport systems for choline and 2-deoxy-D-glucose were stable under the same conditions.", "contents": "Cell cycle and growth stage-dependent changes in the transport of nucleosides, hypoxanthine, choline, and deoxyglucose in cultured Novikoff rat hepatoma cells. Populations of Novikoff rat hepatoma cells (subline N1S1-67) were monitored for the rates of transport of various substrates and for their incorporation into acid-insoluble material as a function of the age of cultures of randomly growing cells in suspension as well as during traverse of the cells through the cell cycle. Populations of cells were synchronized by a double hydroxyurea block or by successive treatment with hydroxyurea and Colcemid. Kinetic analyses showed that changes in transport rates related to the age of cultures or the cell cycle stage reflecte alterations in the V max of the transport processes, whereas the Km remained constant, indicating that changes in transport rates reflect alterations in the number of functional transport sites. The transport sites for uridine and 2-deoxy-D-glucose increased continuously during traverse of the cells through the cell cycle, whereas those for choline and hypoxanthine were formed early in the cell cycle. Increases in thymidine transport sites were confined to the S phase. Synchronized cells deprived of serum failed to exhibit normal increases in transport sites, although the cells divided normally at the end of the cell cycle. Arrest of the cells in mitosis by treatment with Colcemid prevented any further increases in transport rates. The formation of functional transport sites was also dependent on de novo synthesis of RNA and protein. Inhibition of DNA synthesis in early S phase inhibited the increase in thymidine transport rates which normally occurs during the S phase, but had no effect on the formation of the other transport systems. Transport rates also fluctuated markedly with the age of the cultures of randomly growing cells, reaching maximum levels in the mid-exponential phase of growth. The transport systems for thymidine and uridine were rapidly lost upon inhibition of protein and RNA synthesis, and thus seem to be metabolically unstable, whereas the transport systems for choline and 2-deoxy-D-glucose were stable under the same conditions."} {"id": "PMID:162792", "title": "Direct biochemical measurements of microtubule assembly and disassembly in Chinese hamster ovary cells. The effect of intercellular contact, cold, D2O, and N6,O2'-dibutyryl cyclic adenosine monophosphate.", "content": "A study was undertaken to develop a means of quantitating the amount of tubulin present as a soluble pool and as intact microtubules in cultured Chinese hamster ovary cells. A procedure was developed in which these cells grown on monolayer culture in Petri dishes were placed in a \"microtubule stabilizing medium\" (MTM) consisting of 50% glycerol, 10% dimethylsulfoxide and sodium phosphate magnesium buffer, as described previously by Filner and Behnke. These cells then were homogenized and the homogenate was spun in the ultracentrifuge. Colchicine binding activity was then determined in the supernates and the pellets. The values, when compared with total colchicine binding activity present in replicate homogenates, were used to determine the percentage of tubulin present as intact microtubules. A statistical analysis of thin sections of cells treated with MTM revealed no statistically significant difference between MTM-treated cells and untreated controls. It was further discovered that the relative amount of colchicine binding activity recovered in the high speed pellet varied dramatically, depending upon the cell number of the culture being studied. Preconfluent cultures showed very low colchicine binding activity averaging less than 5%, while confluent and postconfluent cultures often possessed as high as 25% of their total colchicine binding activity in pelletable material. Although cold and D2O treatment had little or no effect on these values, N6,O2'-dibutyryl cyclic adenosine monophosphate increased them. It is hoped that this study will serve as the basis for a reliable quantitative procedure for measuring microtubule polymerization and depolymerization in vivo.", "contents": "Direct biochemical measurements of microtubule assembly and disassembly in Chinese hamster ovary cells. The effect of intercellular contact, cold, D2O, and N6,O2'-dibutyryl cyclic adenosine monophosphate. A study was undertaken to develop a means of quantitating the amount of tubulin present as a soluble pool and as intact microtubules in cultured Chinese hamster ovary cells. A procedure was developed in which these cells grown on monolayer culture in Petri dishes were placed in a \"microtubule stabilizing medium\" (MTM) consisting of 50% glycerol, 10% dimethylsulfoxide and sodium phosphate magnesium buffer, as described previously by Filner and Behnke. These cells then were homogenized and the homogenate was spun in the ultracentrifuge. Colchicine binding activity was then determined in the supernates and the pellets. The values, when compared with total colchicine binding activity present in replicate homogenates, were used to determine the percentage of tubulin present as intact microtubules. A statistical analysis of thin sections of cells treated with MTM revealed no statistically significant difference between MTM-treated cells and untreated controls. It was further discovered that the relative amount of colchicine binding activity recovered in the high speed pellet varied dramatically, depending upon the cell number of the culture being studied. Preconfluent cultures showed very low colchicine binding activity averaging less than 5%, while confluent and postconfluent cultures often possessed as high as 25% of their total colchicine binding activity in pelletable material. Although cold and D2O treatment had little or no effect on these values, N6,O2'-dibutyryl cyclic adenosine monophosphate increased them. It is hoped that this study will serve as the basis for a reliable quantitative procedure for measuring microtubule polymerization and depolymerization in vivo."} {"id": "PMID:162797", "title": "Unlimited division potential of precancerous mouse mammary cells after spontaneous or carcinogen-induced transformation.", "content": "Serial transplantation of normal mouse mammary gland in young, isogenic hosts results in progressive loss of division potential, and the transplant line is eventually lost. This is interpreted as an expression of senescence at the cell and tissue level, and it inevitably occurs even though experimental conditions for growth are judged to be optimal. An indefinite extension of mammary growth span can be accomplished by transformation of these normal cells into precancerous cell types, which grow as a benign tissue but which may, however, occasionally undergo a second transformation into a malignant carcinoma. All precancerous tissues tested displayed unlimited growth potential, regardless of whether they occurred spontaneously, or were induced by oncogenic viruses or by administration of chemical carcinogens. Precancerous tissues of both ductal and lobuloalveolar morphology grew continuously. These results indicate that release from cell aging, as measured by the acquisition of unlimited growth potential, is associated with the precancerous state per se, and occurs as an early event in the transition from normal to malignant mammary cells.", "contents": "Unlimited division potential of precancerous mouse mammary cells after spontaneous or carcinogen-induced transformation. Serial transplantation of normal mouse mammary gland in young, isogenic hosts results in progressive loss of division potential, and the transplant line is eventually lost. This is interpreted as an expression of senescence at the cell and tissue level, and it inevitably occurs even though experimental conditions for growth are judged to be optimal. An indefinite extension of mammary growth span can be accomplished by transformation of these normal cells into precancerous cell types, which grow as a benign tissue but which may, however, occasionally undergo a second transformation into a malignant carcinoma. All precancerous tissues tested displayed unlimited growth potential, regardless of whether they occurred spontaneously, or were induced by oncogenic viruses or by administration of chemical carcinogens. Precancerous tissues of both ductal and lobuloalveolar morphology grew continuously. These results indicate that release from cell aging, as measured by the acquisition of unlimited growth potential, is associated with the precancerous state per se, and occurs as an early event in the transition from normal to malignant mammary cells."} {"id": "PMID:162798", "title": "Contributions of cytoplasmic factors to in vitro cellular senescence.", "content": "Mass populations of normal human lung fibroblasts were enucleated by centrifugation at greater than or equal to 25,000 g in 4 mug/ml cytochalasin B. The 1 per cent of cells that did not enucleate where rendered nonviable by treatment with mitomycin C. Whole cells were poisoned with a 99 per cent lethal dose of the sulfhydryl reagent iodoacetate. The washed cells were then mixed with the anucleate cytoplasms, fused with inactivated Sendai virus, and planted in rotenone for 20 hours. Whereas normal cells are able to survive this rotenone treatment, the 1 per cent surviving iodoacetate-treated cells cannot withstand this additional stress. However, iodoacetate treated cells that fuse to untreated cytoplasms receive sufficient amounts of active enzymes to allow them to survive. Since this selective system does not rely on using enzymatic mutants, it should permit the selection of hybrids between anucleate cytoplasms and any type of whole cell. Cytoplasmic hybrids were cultured in order to determine their proliferative capacity. The life-spans of cytoplasmic hybrids between young and old cells were compared to those of young/young and old/old controls. Cytoplasmic factors do not appear to control in vitro cellular senescence.", "contents": "Contributions of cytoplasmic factors to in vitro cellular senescence. Mass populations of normal human lung fibroblasts were enucleated by centrifugation at greater than or equal to 25,000 g in 4 mug/ml cytochalasin B. The 1 per cent of cells that did not enucleate where rendered nonviable by treatment with mitomycin C. Whole cells were poisoned with a 99 per cent lethal dose of the sulfhydryl reagent iodoacetate. The washed cells were then mixed with the anucleate cytoplasms, fused with inactivated Sendai virus, and planted in rotenone for 20 hours. Whereas normal cells are able to survive this rotenone treatment, the 1 per cent surviving iodoacetate-treated cells cannot withstand this additional stress. However, iodoacetate treated cells that fuse to untreated cytoplasms receive sufficient amounts of active enzymes to allow them to survive. Since this selective system does not rely on using enzymatic mutants, it should permit the selection of hybrids between anucleate cytoplasms and any type of whole cell. Cytoplasmic hybrids were cultured in order to determine their proliferative capacity. The life-spans of cytoplasmic hybrids between young and old cells were compared to those of young/young and old/old controls. Cytoplasmic factors do not appear to control in vitro cellular senescence."} {"id": "PMID:162799", "title": "Neuronal--glial interactions during development and aging.", "content": "Integration of the central nervous system is an expression of cerebral homeostasis that is essential for the internal ability of the organism to adapt to its changing environment throughout life. It is generally accepted that neurons undergo no further division after differentiation, whereas glial cells continue to proliferate throughout life. The increase in glial cells with advanced age may reflect a compensatory process of the brain to overcome neuronal loss or neuronal functional changes that may occur with age. Therefore, these neuronal-glial interactions during development and aging may play a key role in the integrative capacity of the brain. One of the mechanisms contributing to brain stability is the blood-brain barrier, which regulates the neuronal-glial microenvironment in the mature organism. Neuronal intercommunication is mediated via neurotransmitter substances and a shift may occur from excitation to inhibition and vice versa in some CNS areas with aging. Studies of some aspects of cholinergic, monoaminergic and amino acid neurotransmission show that their maturational patterns are CNS-area specific and that some neurotransmitter processes decline with advanced age. Glial cells, besides participating in the regulation of extraneuronal environment, are also proposed to be involved in neurotransmission mechanisms in the adult and aging CNS and since they are the major CNS cellular compartment that changes with age they may thus contribute significantly to the maintenance of CNS integrative ability and adaptation with age.", "contents": "Neuronal--glial interactions during development and aging. Integration of the central nervous system is an expression of cerebral homeostasis that is essential for the internal ability of the organism to adapt to its changing environment throughout life. It is generally accepted that neurons undergo no further division after differentiation, whereas glial cells continue to proliferate throughout life. The increase in glial cells with advanced age may reflect a compensatory process of the brain to overcome neuronal loss or neuronal functional changes that may occur with age. Therefore, these neuronal-glial interactions during development and aging may play a key role in the integrative capacity of the brain. One of the mechanisms contributing to brain stability is the blood-brain barrier, which regulates the neuronal-glial microenvironment in the mature organism. Neuronal intercommunication is mediated via neurotransmitter substances and a shift may occur from excitation to inhibition and vice versa in some CNS areas with aging. Studies of some aspects of cholinergic, monoaminergic and amino acid neurotransmission show that their maturational patterns are CNS-area specific and that some neurotransmitter processes decline with advanced age. Glial cells, besides participating in the regulation of extraneuronal environment, are also proposed to be involved in neurotransmission mechanisms in the adult and aging CNS and since they are the major CNS cellular compartment that changes with age they may thus contribute significantly to the maintenance of CNS integrative ability and adaptation with age."} {"id": "PMID:162800", "title": "Bioenergetic functions of sleep and activity rhythms and their possible relevance to aging.", "content": "The hypothesis is proposed that sleep constitutes a period of dormancy in which energy is conserved to partially offset the increased energy demands of homeothermy. Phylogenetic data indicate that the complete psysiological and behavioral manifestations of sleep are unique to homeotherms; furthermore \"ontogeny recapitulates phylogeny\" in the parallel development of slow wave sleep and thermoregulation as exemplified in the opossum. Thus, sleep constitutes a state of reduced metabolism that may represent a variation on the theme of dormancy, functionally lying on a continuum of energy conservation processes, ranging from inactivity and estivation to torpor and hibernation. The high amounts of sleep in infancy may involve conservation of energy and its consequent availability for growth. Decreased amounts of stage 4 and total sleep with aging in humans may represent reduced energy demands reflected by parallel declines in basal metabolic rate and physical activity. Disruptions of circadian rhythms of sleep and wakefulness in humans produce impairments in mood and performance independent of total amounts of sleep obtained, and reduce the amplitude of physiological rhythms. It is suggested that aging processes might also be affected by such disruptions in activity rhythms.", "contents": "Bioenergetic functions of sleep and activity rhythms and their possible relevance to aging. The hypothesis is proposed that sleep constitutes a period of dormancy in which energy is conserved to partially offset the increased energy demands of homeothermy. Phylogenetic data indicate that the complete psysiological and behavioral manifestations of sleep are unique to homeotherms; furthermore \"ontogeny recapitulates phylogeny\" in the parallel development of slow wave sleep and thermoregulation as exemplified in the opossum. Thus, sleep constitutes a state of reduced metabolism that may represent a variation on the theme of dormancy, functionally lying on a continuum of energy conservation processes, ranging from inactivity and estivation to torpor and hibernation. The high amounts of sleep in infancy may involve conservation of energy and its consequent availability for growth. Decreased amounts of stage 4 and total sleep with aging in humans may represent reduced energy demands reflected by parallel declines in basal metabolic rate and physical activity. Disruptions of circadian rhythms of sleep and wakefulness in humans produce impairments in mood and performance independent of total amounts of sleep obtained, and reduce the amplitude of physiological rhythms. It is suggested that aging processes might also be affected by such disruptions in activity rhythms."} {"id": "PMID:162801", "title": "A multisomatic axon in the central nervous system of the leech.", "content": "There is one particularly large axon in the medial bundle of the nerve cord of the leech. It extends along the entire length of the cord and is connected to a single cell body in each ganglion. The cell bodies in adjacent ganglia are tightly electrically coupled, and dye injected into one cell body can diffuse along the axon and into the cell body of the next ganglion. If the nerve cord is cut between two ganglia, neither end of the axon degenerates. Repair of the axon appears to occur by end-to-end fusion.", "contents": "A multisomatic axon in the central nervous system of the leech. There is one particularly large axon in the medial bundle of the nerve cord of the leech. It extends along the entire length of the cord and is connected to a single cell body in each ganglion. The cell bodies in adjacent ganglia are tightly electrically coupled, and dye injected into one cell body can diffuse along the axon and into the cell body of the next ganglion. If the nerve cord is cut between two ganglia, neither end of the axon degenerates. Repair of the axon appears to occur by end-to-end fusion."} {"id": "PMID:162802", "title": "Collagenase in the treatment of dermal and decubitus ulcers.", "content": "The current management of decubitus ulcers, factors in wound healing and the role of enzymes in treatment are discussed. The therapeutic benefits of collagenase (Santyl) ointment in 21 patients are described, supplemented by serial color photographs. Statistical evidence is provided for the conclusion that collagenase ointment is an excellent adjunct to therapy.", "contents": "Collagenase in the treatment of dermal and decubitus ulcers. The current management of decubitus ulcers, factors in wound healing and the role of enzymes in treatment are discussed. The therapeutic benefits of collagenase (Santyl) ointment in 21 patients are described, supplemented by serial color photographs. Statistical evidence is provided for the conclusion that collagenase ointment is an excellent adjunct to therapy."} {"id": "PMID:162806", "title": "Parthenogenic origin of benign ovarian teratomas.", "content": "To determine the origin of benign cystic teratomas of the ovary, chromosome-banding studies were done on normal tissues and teratomas from five patients. The normal tissues were heterozygous (+/-) for 17 chromosome polymorphisms at or near the centromere, whereas the teratomas were uniformly homozygous (+/+ or -/-). These findings and those employing electrophoretic variants indicate that ovarian teratomas are parthenogenic tumors that arise from a single germ cell after the first meiotic division.", "contents": "Parthenogenic origin of benign ovarian teratomas. To determine the origin of benign cystic teratomas of the ovary, chromosome-banding studies were done on normal tissues and teratomas from five patients. The normal tissues were heterozygous (+/-) for 17 chromosome polymorphisms at or near the centromere, whereas the teratomas were uniformly homozygous (+/+ or -/-). These findings and those employing electrophoretic variants indicate that ovarian teratomas are parthenogenic tumors that arise from a single germ cell after the first meiotic division."} {"id": "PMID:162812", "title": "The neurological deficit associated with sudden occlusion of abdominal aorta due to blunt trauma.", "content": "A review of the literature revealed five well-documented cases of abdominal aortic injury due to blunt, nonpenetrating trauma. An additional case report is offered. In all cases the level of aortic injury was at or distal to the origin of the inferior mesenteric artery. In five of these reports, including the present case, sudden traumatic occlusion of the distal abdominal aorta occurred and led to associated neurological deficit. The authors submit, based on clinical manifestations, selective angiography of spinal cord vasculature, and the operative experience of others, that these neurological deficits resulted from acute peripheral nerve ischemia and not from spinal cord ischemia as had been assumed in the past. The final neurological deficit due to acute peripheral nerve ischemia may masquerade as that seen with a \"transverse\" spinal cord lesion. However, the prognosis for recovery of neurological function differs markedly between the two conditions. All surviving patients experienced rapid resolution of their neurological deficits in the immediate postoperative period. Infrarenal aortic occlusion will not produce spinal cord infarction.", "contents": "The neurological deficit associated with sudden occlusion of abdominal aorta due to blunt trauma. A review of the literature revealed five well-documented cases of abdominal aortic injury due to blunt, nonpenetrating trauma. An additional case report is offered. In all cases the level of aortic injury was at or distal to the origin of the inferior mesenteric artery. In five of these reports, including the present case, sudden traumatic occlusion of the distal abdominal aorta occurred and led to associated neurological deficit. The authors submit, based on clinical manifestations, selective angiography of spinal cord vasculature, and the operative experience of others, that these neurological deficits resulted from acute peripheral nerve ischemia and not from spinal cord ischemia as had been assumed in the past. The final neurological deficit due to acute peripheral nerve ischemia may masquerade as that seen with a \"transverse\" spinal cord lesion. However, the prognosis for recovery of neurological function differs markedly between the two conditions. All surviving patients experienced rapid resolution of their neurological deficits in the immediate postoperative period. Infrarenal aortic occlusion will not produce spinal cord infarction."} {"id": "PMID:162813", "title": "Hemoperitoneum from liver cell adenoma in a patient on oral contraceptives.", "content": "A case of hemoperitoneum from ruptured benign liver cell adenoma in a young woman with a long history of oral contraceptive use is presented. The importance of recognizing the cause of this intra-abdominal emergency is stressed, and comment is made about the entity occurring in women on contraceptive drugs.", "contents": "Hemoperitoneum from liver cell adenoma in a patient on oral contraceptives. A case of hemoperitoneum from ruptured benign liver cell adenoma in a young woman with a long history of oral contraceptive use is presented. The importance of recognizing the cause of this intra-abdominal emergency is stressed, and comment is made about the entity occurring in women on contraceptive drugs."} {"id": "PMID:162814", "title": "The significance of elongation and angulation of the carotid artery: a negative view.", "content": "Many authors have postulated that angulation of the carotid artery is a cause of stroke and recommend corrective operation. Symptoms attributed to such lesions are often nebulous and unrelieved by the operation, and proof is lacking that unselected patients who have this condition have a risk of stroke exceeding operative risk. A review of 282 cerebral angiograms showed an incidence of elongation and potential angulation of 43 percent in children and 20 percent in adults. Acutal angulation was not found in children, however, and no child was suspected of having cerebral ischemia. Of 47 adults with potential angulation, 17 were suspected of having cerebral ischemia, the remainder having a variety of other lesions, such as tumors, aneurysm, and intracranial hemorrhage. Of the 17 having suspected cerebral ischemia, all had alternative explanations for their symptoms (hypertension, intracranial atherosclerosis), except one whose symptoms were completely inappropriate to the carotid distribution. A single patient had a completed stroke, demonstrable angulation, and only mild hypertension. Elongation and potential angulation of the carotid artery is common but usually coexists with other lesions. If the finding is postulated as the cause for neurologic morbidity the surgeon must be assured that symptoms are clearly neurologic, that no other cause exists, that angulation reduces the carotid lumen significantly and reproduces symptoms, and that the risk of operation is less than the expected risk of stroke in untreated patients.", "contents": "The significance of elongation and angulation of the carotid artery: a negative view. Many authors have postulated that angulation of the carotid artery is a cause of stroke and recommend corrective operation. Symptoms attributed to such lesions are often nebulous and unrelieved by the operation, and proof is lacking that unselected patients who have this condition have a risk of stroke exceeding operative risk. A review of 282 cerebral angiograms showed an incidence of elongation and potential angulation of 43 percent in children and 20 percent in adults. Acutal angulation was not found in children, however, and no child was suspected of having cerebral ischemia. Of 47 adults with potential angulation, 17 were suspected of having cerebral ischemia, the remainder having a variety of other lesions, such as tumors, aneurysm, and intracranial hemorrhage. Of the 17 having suspected cerebral ischemia, all had alternative explanations for their symptoms (hypertension, intracranial atherosclerosis), except one whose symptoms were completely inappropriate to the carotid distribution. A single patient had a completed stroke, demonstrable angulation, and only mild hypertension. Elongation and potential angulation of the carotid artery is common but usually coexists with other lesions. If the finding is postulated as the cause for neurologic morbidity the surgeon must be assured that symptoms are clearly neurologic, that no other cause exists, that angulation reduces the carotid lumen significantly and reproduces symptoms, and that the risk of operation is less than the expected risk of stroke in untreated patients."} {"id": "PMID:162815", "title": "Experimental and clinical experience with hyperbaric oxygen in the treatment of clostridial myonecrosis.", "content": "At Duke University Medical Center, 49 patients with proved clostridial myonecrosis were treated with hyperbaric oxygen (HBO) during the past 10 years. Survival in patients with involvement confined to the extremities was 92.3 percent. Survival in patients with combined involvement of extremity and trunk was 53-3 percent, and with primary trunk involvement half of the patients survived. Survival for the entire series was 73.5 percent. Among the 28 patients receiving at least five HBO treatments, 24 survived. Extensive experimental studies were conducted during this same period including in vitro testing and in vivo experimental infections with C. perfringens. Data from the experimental models of gas gangrene indicate a therapeutic benefit with HBO by significantly decreasing both mortality and morbidity rates. The mechanism of action for this appears to be complex but probably includes a direct bactericidal action, bacteriostasis, inhibition of toxin production, and improvement in tissue oxygenation. In the absence of a controlled study, the therapeutic efficacy of HBO in the treatment of clostridial myonecrosis is not fully proved. Nevertheless HBO treatment can be recommended on the bases of sound experimental evidence and the results of favorable clinical experience. Mitigation of this severe but infrequent illness can best be accomplished through prevention, with strict adherence to the principles of wound care.", "contents": "Experimental and clinical experience with hyperbaric oxygen in the treatment of clostridial myonecrosis. At Duke University Medical Center, 49 patients with proved clostridial myonecrosis were treated with hyperbaric oxygen (HBO) during the past 10 years. Survival in patients with involvement confined to the extremities was 92.3 percent. Survival in patients with combined involvement of extremity and trunk was 53-3 percent, and with primary trunk involvement half of the patients survived. Survival for the entire series was 73.5 percent. Among the 28 patients receiving at least five HBO treatments, 24 survived. Extensive experimental studies were conducted during this same period including in vitro testing and in vivo experimental infections with C. perfringens. Data from the experimental models of gas gangrene indicate a therapeutic benefit with HBO by significantly decreasing both mortality and morbidity rates. The mechanism of action for this appears to be complex but probably includes a direct bactericidal action, bacteriostasis, inhibition of toxin production, and improvement in tissue oxygenation. In the absence of a controlled study, the therapeutic efficacy of HBO in the treatment of clostridial myonecrosis is not fully proved. Nevertheless HBO treatment can be recommended on the bases of sound experimental evidence and the results of favorable clinical experience. Mitigation of this severe but infrequent illness can best be accomplished through prevention, with strict adherence to the principles of wound care."} {"id": "PMID:162820", "title": "The pathology of Tangier disease. A light and electron microscopic study.", "content": "Tangier disease (deficiency of high density plasma lipoproteins) is characterized clinically by: low levels of plasma cholesterol; enlarged, orange-yellow to yellow-gray tonsils and, frequently, peripheral neuropathy. Histologic and ultrastructural studies were made of various tissues from 5 patients with Tangier disease, and comparisons were made of these findings with those in the 12 other patients thus far known to have this disease. Deposits of cholesteryl esters were found in: reticuloendothelial cells (foam cells) in tonsils, bone marrow, skin and jejunal submucosa; Schwann cells in peripheral nerves and myenteric plexus; and in nonvascular smooth muscle cells. These deposits appeared electron lucent and intensely birefringent, varied from spherical to crystalline in shape, often were extensively confluent throughout large areas of cytoplasm, and were not limited by membranes. Certain foam cells in bone marrow also contained membrane-limited clusters of lipid particles resembling chylomicrons. The foam cells in Tangier disease differ morphologically from those in numerous lysosomal enzyme deficiency states, particularly Wolman's disease and cholesteryl ester stroage disease, and in proliferative diseases of the reticuloendothelial system in which cholesteryl esters also accumulate in abnormal histiocytes. Morphologic and biochemical data suggest several hypotheses to explain the accumulation of cholesteryl esters in tissues of patients with Tangier disease. Among these hypotheses, the most likely are considered to be the presence in plasma of abnormal lipoprotein particles that are subject to phagocytic removal by reticuloendothelial cells, and the failure of a process that normally removes locally synthesized cholesterol from cells to plasma. (Am J Pathol 78:101-158, 1975)", "contents": "The pathology of Tangier disease. A light and electron microscopic study. Tangier disease (deficiency of high density plasma lipoproteins) is characterized clinically by: low levels of plasma cholesterol; enlarged, orange-yellow to yellow-gray tonsils and, frequently, peripheral neuropathy. Histologic and ultrastructural studies were made of various tissues from 5 patients with Tangier disease, and comparisons were made of these findings with those in the 12 other patients thus far known to have this disease. Deposits of cholesteryl esters were found in: reticuloendothelial cells (foam cells) in tonsils, bone marrow, skin and jejunal submucosa; Schwann cells in peripheral nerves and myenteric plexus; and in nonvascular smooth muscle cells. These deposits appeared electron lucent and intensely birefringent, varied from spherical to crystalline in shape, often were extensively confluent throughout large areas of cytoplasm, and were not limited by membranes. Certain foam cells in bone marrow also contained membrane-limited clusters of lipid particles resembling chylomicrons. The foam cells in Tangier disease differ morphologically from those in numerous lysosomal enzyme deficiency states, particularly Wolman's disease and cholesteryl ester stroage disease, and in proliferative diseases of the reticuloendothelial system in which cholesteryl esters also accumulate in abnormal histiocytes. Morphologic and biochemical data suggest several hypotheses to explain the accumulation of cholesteryl esters in tissues of patients with Tangier disease. Among these hypotheses, the most likely are considered to be the presence in plasma of abnormal lipoprotein particles that are subject to phagocytic removal by reticuloendothelial cells, and the failure of a process that normally removes locally synthesized cholesterol from cells to plasma. (Am J Pathol 78:101-158, 1975)"} {"id": "PMID:162821", "title": "Gastric organ culture. A model for reepithelialization.", "content": "The in vitro organ culture system is useful in the study of the mechanics of gastric reepithelialization, cell migration and exfoliation. Reepithelialization is apparently effected by actively motile cells of all levels of differentiation, and at the completion of the process a new zone of cell exfoliation is initiated at points of contact when cells meet after growing towards the center of the specimen from its opposite margins. Mitotic activity is suppressed during the period of migration. (Am J Pathol 78:23-32, 1975)", "contents": "Gastric organ culture. A model for reepithelialization. The in vitro organ culture system is useful in the study of the mechanics of gastric reepithelialization, cell migration and exfoliation. Reepithelialization is apparently effected by actively motile cells of all levels of differentiation, and at the completion of the process a new zone of cell exfoliation is initiated at points of contact when cells meet after growing towards the center of the specimen from its opposite margins. Mitotic activity is suppressed during the period of migration. (Am J Pathol 78:23-32, 1975)"} {"id": "PMID:162822", "title": "Leukemic mitochondria. III. Acute lymphoblastic leukemia.", "content": "Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic lymphoblasts in 6 patients with acute lymphoblastic leukemia. Similar studies were performed on lymphoblasts from lymph nodes obtained from 10 surgical patients without nodal diseases. Significant quantitative differences between normal and leukemic mitochondria were not observed except for a difference in mitochondrial area per cell (P less than 0.05). This was not significant lacking, qualitative diffecrences were observed. These abnormalities included rare giant mitochondria, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and nucleus during interphase. Fifty-three percent of the leukemic lymphoblasts contained polyribosomes, as compared to 25% of the normal lymphoblasts. The cells with the polyribosomes contained the giant mitochondria. The leukemic lymphoblasts had an appearance similar to transformed lymphocytes resulting from an immunologic stimulus. This suggests that acute lymphoblastic leukemia may be a disease which is associated with an immunologic response. From the available ultrastructural and biochemical data, it would seem that the leukemic lymphoblast is a product of an abnormal metabolism which affects its ability to differentiate. These ultrastructural findings seem to indicate the need for biochemical investigation of leukemic mitochondria. (Am J Pathol 78:49-58, 1975", "contents": "Leukemic mitochondria. III. Acute lymphoblastic leukemia. Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic lymphoblasts in 6 patients with acute lymphoblastic leukemia. Similar studies were performed on lymphoblasts from lymph nodes obtained from 10 surgical patients without nodal diseases. Significant quantitative differences between normal and leukemic mitochondria were not observed except for a difference in mitochondrial area per cell (P less than 0.05). This was not significant lacking, qualitative diffecrences were observed. These abnormalities included rare giant mitochondria, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and nucleus during interphase. Fifty-three percent of the leukemic lymphoblasts contained polyribosomes, as compared to 25% of the normal lymphoblasts. The cells with the polyribosomes contained the giant mitochondria. The leukemic lymphoblasts had an appearance similar to transformed lymphocytes resulting from an immunologic stimulus. This suggests that acute lymphoblastic leukemia may be a disease which is associated with an immunologic response. From the available ultrastructural and biochemical data, it would seem that the leukemic lymphoblast is a product of an abnormal metabolism which affects its ability to differentiate. These ultrastructural findings seem to indicate the need for biochemical investigation of leukemic mitochondria. (Am J Pathol 78:49-58, 1975"} {"id": "PMID:162823", "title": "Ultrastructural studies of parallel tubular arrays in human lymphocytes.", "content": "Parallel tubular inclusions were found in peripheral blood lymphocytes from 18 patients with various hematologic disorders, primarily lymphoproliferative processes, and 1 apparently healthy individual. The inclusions varied in size from 1000 to 6000 A and were usually membrane bounded. The microtubule-like structures comprising the inclusions ranged in size from 150 to 300 A and were packed in wall-to-wall contact with each other. Dense amorphous material and small dark crystalloids were frequently noted in the inclusions. There appeared to be a spatial and structural relationship of the inclusions with the centriole. The highest percent of lymphocytes with inclusionss (greater than 90%) were found in a patient with a lympho-proliferative disorder in whom 95% of the peripheral blood lymphocytes typed as T cells by spontaneous rosette formation with sheep red blood cells. (Am J Pathol 78:59-70, 1975)", "contents": "Ultrastructural studies of parallel tubular arrays in human lymphocytes. Parallel tubular inclusions were found in peripheral blood lymphocytes from 18 patients with various hematologic disorders, primarily lymphoproliferative processes, and 1 apparently healthy individual. The inclusions varied in size from 1000 to 6000 A and were usually membrane bounded. The microtubule-like structures comprising the inclusions ranged in size from 150 to 300 A and were packed in wall-to-wall contact with each other. Dense amorphous material and small dark crystalloids were frequently noted in the inclusions. There appeared to be a spatial and structural relationship of the inclusions with the centriole. The highest percent of lymphocytes with inclusionss (greater than 90%) were found in a patient with a lympho-proliferative disorder in whom 95% of the peripheral blood lymphocytes typed as T cells by spontaneous rosette formation with sheep red blood cells. (Am J Pathol 78:59-70, 1975)"} {"id": "PMID:162824", "title": "Comparison of the effects of histamine and tolazoline on adenylate cyclase activity from guinea pig heart.", "content": "Both histamine and tolazoline (2-benzyl-2-imidazoline) stimulated particulate fractions of adenylate cyclase from guinea pig myocardium. Tolazoline was one-tenth as potent, and about two-thirds as active at maximally effective levels, as was histamine. Enhancement of cyclase activity by tolazoline was additive with that by isoproterenol, and the histamine and tolazoline concentration-response curves were parallel, suggesting that tolazoline acted at the same site as histamine. At maximally effective concentrations, tolazoline did not affect ATPase or cyclic AMP phosphodiesterase activities associated with the cyclase preparations. The H1-receptor antagonist mepyramine, and the H2 antagonist, burimamide, blocked stimulation of cyclase by tolazoline at one-tenth the molarity of agonist. Both antagonists were less effective vs. histamine stimulation of heart cyclase in particulate fractions or whole homogenates, with mepyramine being generally more potent. It is suggested that the molecular basis of the stimulatory effect of tolazoline on cardiac tissue may be histaminergic stimulation of adenylate cyclase. Furthermore, the lack of potency of burimamide as a histamine antagonist and its lack of specificity compared to mepyramine, at the subcellular level, indicate that histamine-responsive adenylate cyclase from heart may not be a satisfactory molecular model for the H2 receptor pharmacology of histamine in cardiac tissue.", "contents": "Comparison of the effects of histamine and tolazoline on adenylate cyclase activity from guinea pig heart. Both histamine and tolazoline (2-benzyl-2-imidazoline) stimulated particulate fractions of adenylate cyclase from guinea pig myocardium. Tolazoline was one-tenth as potent, and about two-thirds as active at maximally effective levels, as was histamine. Enhancement of cyclase activity by tolazoline was additive with that by isoproterenol, and the histamine and tolazoline concentration-response curves were parallel, suggesting that tolazoline acted at the same site as histamine. At maximally effective concentrations, tolazoline did not affect ATPase or cyclic AMP phosphodiesterase activities associated with the cyclase preparations. The H1-receptor antagonist mepyramine, and the H2 antagonist, burimamide, blocked stimulation of cyclase by tolazoline at one-tenth the molarity of agonist. Both antagonists were less effective vs. histamine stimulation of heart cyclase in particulate fractions or whole homogenates, with mepyramine being generally more potent. It is suggested that the molecular basis of the stimulatory effect of tolazoline on cardiac tissue may be histaminergic stimulation of adenylate cyclase. Furthermore, the lack of potency of burimamide as a histamine antagonist and its lack of specificity compared to mepyramine, at the subcellular level, indicate that histamine-responsive adenylate cyclase from heart may not be a satisfactory molecular model for the H2 receptor pharmacology of histamine in cardiac tissue."} {"id": "PMID:162825", "title": "Interrelationships between synthesis and methylation of ribosomal RNA in isolated Novikoff Tumor nucleoli.", "content": "Nucleoli isolated from Novikoff hepatoma cells of the rat were previously shown to carry out synthesis of predominantly ribosomal precursor RNA and methylation of this RNA in vitro. In order to develop in vitro systems for further detailed study of these processes and their interrelationships, isolated nucleoli were incubated in a complete RNA-synthesizing medium using (5-3H)cytidine 5'-triphosphate or S-adenoxyl(methyl-3H)methionine to measure the activities of RNA synthesis and methylation, respectively, under the same reaction conditions. Methylation of the ribose of the nascent ribosomal precursor RNA predominated. It occurred in close coordination with the transcriptional step by RNA polymerase as shown by the kinetic data, the analysis of labeled RNA in sucrose gradients, the inhibition by increased ionic strength or actinomycin D, and the release of labeled nucleotides by a 3'-exonuclease, venom phosphodiesterase. Methylation of the RNA bases occurred more slowly, continued longer after transcription ceased, and appeared to follow later in the processing of the RNA. Certain divalent cations (Mg2+, Mn2+, and Ca2+ at higher concentrations, and Zn2+ and Cu2+) inhibited both RNA synthesis and methylation to similar extents. RNase inhibitors (bentonite and dextran sulfate) at low concentration inhibited methylation while stimulating RNA synthesis, and pyrophosphate greatly decreased RNA synthesis with relatively little effect on methylation. These results indicated that RNA polymerase and ribosomal RNA methylases can function independently despite their close relationship. An exogenous substrate for the nucleolar rRNA methylases was found: nuclear RNA prepared from Novikoff hepatoma cells, cultured in the absence of methionine, served as a good substrate for methylation of both ribose and bases. Other exogenous RNAs, including cytoplasmic ribosomal RNA from these methionine-starved cells, nucleolar RNA from normal cells, and wheat germ ribosomal RNA were almost devoid of methyl-acceptor activity. A description of these parameters helps establish isolated nucleoli as a suitable system for further study of interaction of RNA polymerase, methylases, and nucleases in control of synthesis of ribosomal RNA.", "contents": "Interrelationships between synthesis and methylation of ribosomal RNA in isolated Novikoff Tumor nucleoli. Nucleoli isolated from Novikoff hepatoma cells of the rat were previously shown to carry out synthesis of predominantly ribosomal precursor RNA and methylation of this RNA in vitro. In order to develop in vitro systems for further detailed study of these processes and their interrelationships, isolated nucleoli were incubated in a complete RNA-synthesizing medium using (5-3H)cytidine 5'-triphosphate or S-adenoxyl(methyl-3H)methionine to measure the activities of RNA synthesis and methylation, respectively, under the same reaction conditions. Methylation of the ribose of the nascent ribosomal precursor RNA predominated. It occurred in close coordination with the transcriptional step by RNA polymerase as shown by the kinetic data, the analysis of labeled RNA in sucrose gradients, the inhibition by increased ionic strength or actinomycin D, and the release of labeled nucleotides by a 3'-exonuclease, venom phosphodiesterase. Methylation of the RNA bases occurred more slowly, continued longer after transcription ceased, and appeared to follow later in the processing of the RNA. Certain divalent cations (Mg2+, Mn2+, and Ca2+ at higher concentrations, and Zn2+ and Cu2+) inhibited both RNA synthesis and methylation to similar extents. RNase inhibitors (bentonite and dextran sulfate) at low concentration inhibited methylation while stimulating RNA synthesis, and pyrophosphate greatly decreased RNA synthesis with relatively little effect on methylation. These results indicated that RNA polymerase and ribosomal RNA methylases can function independently despite their close relationship. An exogenous substrate for the nucleolar rRNA methylases was found: nuclear RNA prepared from Novikoff hepatoma cells, cultured in the absence of methionine, served as a good substrate for methylation of both ribose and bases. Other exogenous RNAs, including cytoplasmic ribosomal RNA from these methionine-starved cells, nucleolar RNA from normal cells, and wheat germ ribosomal RNA were almost devoid of methyl-acceptor activity. A description of these parameters helps establish isolated nucleoli as a suitable system for further study of interaction of RNA polymerase, methylases, and nucleases in control of synthesis of ribosomal RNA."} {"id": "PMID:162826", "title": "Ligand binding and enzymic catalysis coupled through subunits in tyrosyl-tRNA synthetase.", "content": "The interaction of the tyrosyl-tRNA synthetase from Bacillus stearothermophilus with its substrates in the aminoacyl adenylation reaction has been studied by stopped-flow fluorescence. The observed changes have been assigned to their chemical and physical processes by comparison with equilibrium dialysis, pyrophosphate exchange kinetics and rapid quenching and sampling techniques to give the rate constants for ligand binding, the formation of tyrosyl adenylate, and the reverse reaction. The stoichiometry of tyrosine and ATP binding in the catalytic process has been determined directly by equilibrium dialysis and equilibrium gel filtration under pyrophosphate exchange conditions, i.e., where a steady state has been set up in which the equilibrium position favors starting materials. It is shown that the rate-determining step in the formation of tyrosyl adenylate involves 1 mole each of tyrosine and ATP. A second mole of tyrosine and ATP bind to the aminoacyl adenylate complex stabilizing the high-energy intermediate. The enzyme tyrosyl adenylate complex that is isolated by gel filtration is in a different conformational state from that in the presence of tyrosine and ATP.", "contents": "Ligand binding and enzymic catalysis coupled through subunits in tyrosyl-tRNA synthetase. The interaction of the tyrosyl-tRNA synthetase from Bacillus stearothermophilus with its substrates in the aminoacyl adenylation reaction has been studied by stopped-flow fluorescence. The observed changes have been assigned to their chemical and physical processes by comparison with equilibrium dialysis, pyrophosphate exchange kinetics and rapid quenching and sampling techniques to give the rate constants for ligand binding, the formation of tyrosyl adenylate, and the reverse reaction. The stoichiometry of tyrosine and ATP binding in the catalytic process has been determined directly by equilibrium dialysis and equilibrium gel filtration under pyrophosphate exchange conditions, i.e., where a steady state has been set up in which the equilibrium position favors starting materials. It is shown that the rate-determining step in the formation of tyrosyl adenylate involves 1 mole each of tyrosine and ATP. A second mole of tyrosine and ATP bind to the aminoacyl adenylate complex stabilizing the high-energy intermediate. The enzyme tyrosyl adenylate complex that is isolated by gel filtration is in a different conformational state from that in the presence of tyrosine and ATP."} {"id": "PMID:162827", "title": "Hydrodynamic diameters of RNA tumor viruses. Studies by laser beat frequency light scattering spectroscopy of avian myeloblastosis and Rauscher murine leukemia viruses.", "content": "The diffusion constants of avian myeloblastosis virus (AMV) and murine leukemia virus (MuLV) (Rauscher) suspensions in buffer and in 30% sucrose were determined by laser beat frequency light scattering spectroscopy at a series of temperatures ranging rom 5 to 25 degrees. By the use of the Stokes-Einstein equation, the following hydrodynamic diameters are calculated at 20 degrees: MuLV, 154 plus or minus 3 nm in sucrose and 145 plus or minus 7 nm in buffer; AMV, 144 plus or minus 3 nm in sucrose and 138 plus or minus 4 nm in buffer. While the diameters measured in buffer were temperature independent, the diameters measured in sucrose decreased by about 20% as the temperature was raised from 5 to 25 degrees. The concentration of virus particles in the suspensions ranged from 10 7 to 10 9 particles/ml. The absolute particle concentrations are estimated within plus or minus 30% by determining the dilution needed to reach a concentration sufficiently low that the particle number fluctuation contribution was comparable to that of the interference scattering. Particle weights of 3.9 x 10 8 daltons for MuLV and 4.0 x 10 8 daltons for AMV were calculated from the diffusion constants and from our own experimentally determined sedimentation coefficients. From these particle weights and the hydrodynamic diameters of the viruses, we calculated the per cent of the hydrodynamic volume of the viruses which could be freely penetrated by water, viz., 57% for AMV and 69% for MuLV.", "contents": "Hydrodynamic diameters of RNA tumor viruses. Studies by laser beat frequency light scattering spectroscopy of avian myeloblastosis and Rauscher murine leukemia viruses. The diffusion constants of avian myeloblastosis virus (AMV) and murine leukemia virus (MuLV) (Rauscher) suspensions in buffer and in 30% sucrose were determined by laser beat frequency light scattering spectroscopy at a series of temperatures ranging rom 5 to 25 degrees. By the use of the Stokes-Einstein equation, the following hydrodynamic diameters are calculated at 20 degrees: MuLV, 154 plus or minus 3 nm in sucrose and 145 plus or minus 7 nm in buffer; AMV, 144 plus or minus 3 nm in sucrose and 138 plus or minus 4 nm in buffer. While the diameters measured in buffer were temperature independent, the diameters measured in sucrose decreased by about 20% as the temperature was raised from 5 to 25 degrees. The concentration of virus particles in the suspensions ranged from 10 7 to 10 9 particles/ml. The absolute particle concentrations are estimated within plus or minus 30% by determining the dilution needed to reach a concentration sufficiently low that the particle number fluctuation contribution was comparable to that of the interference scattering. Particle weights of 3.9 x 10 8 daltons for MuLV and 4.0 x 10 8 daltons for AMV were calculated from the diffusion constants and from our own experimentally determined sedimentation coefficients. From these particle weights and the hydrodynamic diameters of the viruses, we calculated the per cent of the hydrodynamic volume of the viruses which could be freely penetrated by water, viz., 57% for AMV and 69% for MuLV."} {"id": "PMID:162828", "title": "Qualitative and quantitative interactions of lectins with untreated and neuraminidase-treated normal, wild-type, and temperature-sensitive polyoma-transformed fibroblasts.", "content": "The lectin receptors of confluently grown hamster BHK, wild type polyoma virus transformed PyBHK, and temperature-sensitive polyoma transformed ts3-PyBHK fibroblasts were investigated using cell agglutination, quantitative (125I)lectin binding, and ferritin-lectin labeling. PyBHK and permissively grown ts3-PyBHK cells agglutinated more strongly with Ricinus communis I agglutinin (RCA-I)compared to BHK and nonpermissively grown ts3-PyBHK, although saturation binding of (125I)RCA-I to these cells at 4 degrees resulted in a twofold difference in lectin-binding sites on BHK and nonpermissively grown ts3-PyBHK cells (1.0-1.3 x 10 7 sites/cell) compared to PyBHK and permissively grown ts3-PyBHK (0.4-0.6 x 10 7 sites/cell). These cells bound equivalent amounts of (125I)concanavalin A (0.8-1 x 10 7 sites/cell) and (125I)wheat germ agglutinin (1-2.2 x 10 7 sites/cell). Under these binding conditions little endocytosis occurred, as judged by the subsequent release of greater than 90% cell-bound (125I)RCA-I by the RCA-I inhibitor lactose and localization of ferritin-RCA-I exclusively to the extracellular plasma membrane surface. However, if the binding is performed at 22 degrees, only 50% of the bound lectin can be removed by lactose, and ferritin-RCA-I is localized inside the cell within endocytotic vesicles. The relative mobility of RCA-I receptors was examined on ts3-PyBHK cells by the ability of ferritin-RCA-I to induce clustering of its receptors at 22 degrees. RCA-I receptors on permissively grown ts3-PyBHK cells appeared to be more mobile than on nonpermissively grown cells. BHK and PyBHK cells were treated with neuraminidase, and the resulting enzyme-treated cells were assayed for lectin agglutinability and quantitative binding of RCA-I, concanavalin A, and wheat germ agglutinin. Neuraminidase treatment resulted in decreased concanavalin A and wheat germ agglutinability and a slight increase in RCA-I agglutinability. The enzyme-treated BHK and PyBHK cells bound less (125I)wheat germ agglutinin (2.8 x 10 6 and 2.2 x 10 6 sites/cell, respectively) and 2.5 and 6.2 times more (125I)RCA-I (2.5-3 x 10 7) and 3.5-4 x 10 7 sites/per cell, respectively). There was no change in the number of concanavalin A binding sites after neuraminidase treatment. The increase in RCA-I binding sites approximated the decrease in wheat germ agglutinin binding sites indicating that the predominant penultimate oligosaccharide residue to sialic acid on these cells is D-Gal.", "contents": "Qualitative and quantitative interactions of lectins with untreated and neuraminidase-treated normal, wild-type, and temperature-sensitive polyoma-transformed fibroblasts. The lectin receptors of confluently grown hamster BHK, wild type polyoma virus transformed PyBHK, and temperature-sensitive polyoma transformed ts3-PyBHK fibroblasts were investigated using cell agglutination, quantitative (125I)lectin binding, and ferritin-lectin labeling. PyBHK and permissively grown ts3-PyBHK cells agglutinated more strongly with Ricinus communis I agglutinin (RCA-I)compared to BHK and nonpermissively grown ts3-PyBHK, although saturation binding of (125I)RCA-I to these cells at 4 degrees resulted in a twofold difference in lectin-binding sites on BHK and nonpermissively grown ts3-PyBHK cells (1.0-1.3 x 10 7 sites/cell) compared to PyBHK and permissively grown ts3-PyBHK (0.4-0.6 x 10 7 sites/cell). These cells bound equivalent amounts of (125I)concanavalin A (0.8-1 x 10 7 sites/cell) and (125I)wheat germ agglutinin (1-2.2 x 10 7 sites/cell). Under these binding conditions little endocytosis occurred, as judged by the subsequent release of greater than 90% cell-bound (125I)RCA-I by the RCA-I inhibitor lactose and localization of ferritin-RCA-I exclusively to the extracellular plasma membrane surface. However, if the binding is performed at 22 degrees, only 50% of the bound lectin can be removed by lactose, and ferritin-RCA-I is localized inside the cell within endocytotic vesicles. The relative mobility of RCA-I receptors was examined on ts3-PyBHK cells by the ability of ferritin-RCA-I to induce clustering of its receptors at 22 degrees. RCA-I receptors on permissively grown ts3-PyBHK cells appeared to be more mobile than on nonpermissively grown cells. BHK and PyBHK cells were treated with neuraminidase, and the resulting enzyme-treated cells were assayed for lectin agglutinability and quantitative binding of RCA-I, concanavalin A, and wheat germ agglutinin. Neuraminidase treatment resulted in decreased concanavalin A and wheat germ agglutinability and a slight increase in RCA-I agglutinability. The enzyme-treated BHK and PyBHK cells bound less (125I)wheat germ agglutinin (2.8 x 10 6 and 2.2 x 10 6 sites/cell, respectively) and 2.5 and 6.2 times more (125I)RCA-I (2.5-3 x 10 7) and 3.5-4 x 10 7 sites/per cell, respectively). There was no change in the number of concanavalin A binding sites after neuraminidase treatment. The increase in RCA-I binding sites approximated the decrease in wheat germ agglutinin binding sites indicating that the predominant penultimate oligosaccharide residue to sialic acid on these cells is D-Gal."} {"id": "PMID:162829", "title": "Rabbit skeletal muscle protein kinase. Conversion from cAMP dependent to independent form by chemical perturbations.", "content": "Protein kinase isolated from rabbit skeletal muscle can be reversibly converted from the cAMP dependent form to the indepent form by chaotropic salts and urea. A similar but irreversible conversion can also be induced by trypsin digestion of the holoenzyme. The dissociation of cAMP dependent protein kinase by low concentrations of thiocyanate raises the possibility of isolating both native regulatory and catalytic subunits. From various changes in enzymatic activity caused by urea and trypsin perturbation, it is proposed that the conversion of protein kinase from the cAMP dependent to the independent form is due primarily to preferential modification of the regulatory subunit of the holoenzyme.", "contents": "Rabbit skeletal muscle protein kinase. Conversion from cAMP dependent to independent form by chemical perturbations. Protein kinase isolated from rabbit skeletal muscle can be reversibly converted from the cAMP dependent form to the indepent form by chaotropic salts and urea. A similar but irreversible conversion can also be induced by trypsin digestion of the holoenzyme. The dissociation of cAMP dependent protein kinase by low concentrations of thiocyanate raises the possibility of isolating both native regulatory and catalytic subunits. From various changes in enzymatic activity caused by urea and trypsin perturbation, it is proposed that the conversion of protein kinase from the cAMP dependent to the independent form is due primarily to preferential modification of the regulatory subunit of the holoenzyme."} {"id": "PMID:162830", "title": "Subcellular distribution of glucocorticoid receptors in mouse fibroblasts.", "content": "Mouse fibroblasts contain a macromolecular binding component (receptor) which binds glucocorticoids specifically and with high affinity. This study shows that there are three different cellular forms of bound receptor and that it is experimentally possible to markedly alter the subcellular distribution of these three forms. Cells incubated with (3H)triamcinolone acetonide were broken after hypotonic shock and a 7000g hypotonic supernatant was obtained; the pellet was extracted with 0.3 M KCl, yielding a nuclear extract; the remaining pellet was resuspended in water, sonicated, and assayed for \"nuclear residual\" (i.e., nonextractable) radioactivity. If whole cells are incubated at 0 degrees in a growth medium, almost all of the bound steroid is located in the hypotonic supernatant fraction. Incubation at 37 degrees produces a shift of the steroid-bound macromolecule into the nuclear extractable form, while omission of glucose and addition of KCN at 37 degrees markedly increase the nuclear residual form at the expense of both the nuclear-extractable and supernatant forms. Since DNase treatment of chromatin liberates a soluble steroid-receptor complex, we believe that the nuclear residual form may be steroid-receptor complex tightly bound to chromatin. We propose a model suggesting that an energy-requiring process is required to generate free receptor from the chromatin complex to complete the normal cellular recycling system.", "contents": "Subcellular distribution of glucocorticoid receptors in mouse fibroblasts. Mouse fibroblasts contain a macromolecular binding component (receptor) which binds glucocorticoids specifically and with high affinity. This study shows that there are three different cellular forms of bound receptor and that it is experimentally possible to markedly alter the subcellular distribution of these three forms. Cells incubated with (3H)triamcinolone acetonide were broken after hypotonic shock and a 7000g hypotonic supernatant was obtained; the pellet was extracted with 0.3 M KCl, yielding a nuclear extract; the remaining pellet was resuspended in water, sonicated, and assayed for \"nuclear residual\" (i.e., nonextractable) radioactivity. If whole cells are incubated at 0 degrees in a growth medium, almost all of the bound steroid is located in the hypotonic supernatant fraction. Incubation at 37 degrees produces a shift of the steroid-bound macromolecule into the nuclear extractable form, while omission of glucose and addition of KCN at 37 degrees markedly increase the nuclear residual form at the expense of both the nuclear-extractable and supernatant forms. Since DNase treatment of chromatin liberates a soluble steroid-receptor complex, we believe that the nuclear residual form may be steroid-receptor complex tightly bound to chromatin. We propose a model suggesting that an energy-requiring process is required to generate free receptor from the chromatin complex to complete the normal cellular recycling system."} {"id": "PMID:162831", "title": "Electron paramagnetic resonance of copper ion and manganese ion complexes with the ionophore A23187.", "content": "The binding of Cu2+ and Mn2+ to the ionophore A23187 in chloroform, 90% ethanol, and sonicated phospholipid dispersions in aqueous mediums has been investigated with electron paramagnetic resonance (epr). The spectra indicated axial symmetry for the Cu2+ complexes and distorted octahedral for the Mn2+ complexes. The coordination between metal ion and its ligands is predominantly ionic in character. The stoichiometry, at the concentrations employed, was found to be 1:2 M2+/ionophore except in 90% ethanol where evidence existed for the 1:1 Cu-A23187 complex, as well. Through competition with Mn2+, the sequence of relative affinities in 90% ethanol was measured to be: Mn2+ greater than La3+ greater than Cu2+ greater than Ca2+ greater than Mg2+ greater than Sr2+. The K A of Mn-A23187 binding is greater than 10 10 M-2. In phospholipid dispersions the spectral characteristics of the Cu complex, particularly g, were observed to be a sensitive function of the hydrocarbon chain mobility. This allowed a calculation of the rotational correlation time of the complex to be made. In sonicated dipalmitoyllecithin was computed to be 10-9 sec, reflecting a local viscosity similar to that sensed by the nitroxide spin-label 2,2,6,6-tetramethylpiperidin-1-oxyl. In a (1:1) lecithin-cholesterol dispersion the complex was significantly more immobilized.", "contents": "Electron paramagnetic resonance of copper ion and manganese ion complexes with the ionophore A23187. The binding of Cu2+ and Mn2+ to the ionophore A23187 in chloroform, 90% ethanol, and sonicated phospholipid dispersions in aqueous mediums has been investigated with electron paramagnetic resonance (epr). The spectra indicated axial symmetry for the Cu2+ complexes and distorted octahedral for the Mn2+ complexes. The coordination between metal ion and its ligands is predominantly ionic in character. The stoichiometry, at the concentrations employed, was found to be 1:2 M2+/ionophore except in 90% ethanol where evidence existed for the 1:1 Cu-A23187 complex, as well. Through competition with Mn2+, the sequence of relative affinities in 90% ethanol was measured to be: Mn2+ greater than La3+ greater than Cu2+ greater than Ca2+ greater than Mg2+ greater than Sr2+. The K A of Mn-A23187 binding is greater than 10 10 M-2. In phospholipid dispersions the spectral characteristics of the Cu complex, particularly g, were observed to be a sensitive function of the hydrocarbon chain mobility. This allowed a calculation of the rotational correlation time of the complex to be made. In sonicated dipalmitoyllecithin was computed to be 10-9 sec, reflecting a local viscosity similar to that sensed by the nitroxide spin-label 2,2,6,6-tetramethylpiperidin-1-oxyl. In a (1:1) lecithin-cholesterol dispersion the complex was significantly more immobilized."} {"id": "PMID:162832", "title": "Thermodynamics of complex formation between nicotinamide adenine dinucleotide and pig skeletal muscle lactate dehydrogenase.", "content": "Formation of the binary complex between the reduced coenzyme nicotinamide adenine dinucleotide (NADH) and pig skeletal muscle lactate dehydrogenase (LDH, EC 1.1.1.27) has been investigated by calorimetric and equilibrium dialysis techniques in 0.2 M potassium phosphate buffer (pH 7.0) at various temperatures. Analysis of thermal titration curves at two temperatures (25 and 31.5 degrees) shows that the experimental enthalpy data can be rationalized assuming four independent and equivalent binding sites for the tetrameric enzyme. Binary complex formation is characterized by a negative temperature coefficient, delta cp, of the binding enthalpy, which amounts to -1300 plus or minus 53 cal/(deg mol of LDH) in the temperature range of 5-31.5 degrees. Despite the slightly smaller standard deviation resulting when polynomial regression analysis of the second degree is applied to the temperature dependence of the enthalpy values, binding enthalpies seem to be adequately represented in the temperature range studied by the equation delta H = -1.3T + 2.3, kcal/mol of LDH, T referring to the temperature in degrees C. By combination of the results obtained from equilibrium dialysis and calorimetric studies a set of apparent thermodynamic parameters for binding of NADH to LDH in 0.2 M potassium phosphate buffer at pH 7 has been established.", "contents": "Thermodynamics of complex formation between nicotinamide adenine dinucleotide and pig skeletal muscle lactate dehydrogenase. Formation of the binary complex between the reduced coenzyme nicotinamide adenine dinucleotide (NADH) and pig skeletal muscle lactate dehydrogenase (LDH, EC 1.1.1.27) has been investigated by calorimetric and equilibrium dialysis techniques in 0.2 M potassium phosphate buffer (pH 7.0) at various temperatures. Analysis of thermal titration curves at two temperatures (25 and 31.5 degrees) shows that the experimental enthalpy data can be rationalized assuming four independent and equivalent binding sites for the tetrameric enzyme. Binary complex formation is characterized by a negative temperature coefficient, delta cp, of the binding enthalpy, which amounts to -1300 plus or minus 53 cal/(deg mol of LDH) in the temperature range of 5-31.5 degrees. Despite the slightly smaller standard deviation resulting when polynomial regression analysis of the second degree is applied to the temperature dependence of the enthalpy values, binding enthalpies seem to be adequately represented in the temperature range studied by the equation delta H = -1.3T + 2.3, kcal/mol of LDH, T referring to the temperature in degrees C. By combination of the results obtained from equilibrium dialysis and calorimetric studies a set of apparent thermodynamic parameters for binding of NADH to LDH in 0.2 M potassium phosphate buffer at pH 7 has been established."} {"id": "PMID:162833", "title": "Multicentric and isolated multifocal glioblastoma multiforme simulating metastatic disease.", "content": "Single case reports of multicentric glioblastoma multiforme and multifocal glioblastoma multiforme tumours are presented. Multicentric glioblastoma multiforme tumours are those which have no macroscopic or microscopic connection. Multifocal gliomatous tumours, on the other hand, are those with either gross or microsopic continuity or evidence of cerebral spinal fluid spread and/or local metastases. The cerebral scintigram findings, cerebral angiogram studies and pathological description of these entities are presented. These lesions may be mistaken for metastases. In patients with multiple cerebral lesions multiple primary malignancies of brain should be considered when there is no clinical or radiographical evidence for extracranial primary neoplasms.", "contents": "Multicentric and isolated multifocal glioblastoma multiforme simulating metastatic disease. Single case reports of multicentric glioblastoma multiforme and multifocal glioblastoma multiforme tumours are presented. Multicentric glioblastoma multiforme tumours are those which have no macroscopic or microscopic connection. Multifocal gliomatous tumours, on the other hand, are those with either gross or microsopic continuity or evidence of cerebral spinal fluid spread and/or local metastases. The cerebral scintigram findings, cerebral angiogram studies and pathological description of these entities are presented. These lesions may be mistaken for metastases. In patients with multiple cerebral lesions multiple primary malignancies of brain should be considered when there is no clinical or radiographical evidence for extracranial primary neoplasms."} {"id": "PMID:162836", "title": "Resuscitation of the monkey brain after one hour's complete ischemia. II. Brain water and electrolytes.", "content": "Adult normothermic rhesus monkeys were submitted to one hour's complete cerebral ischemia, followed by periods of blood recirculation varying from 45 min to 24 h. The functional impact of ischemia and the subsequent recovery was monitored by electrophysiological recording and a distinction was made between animals with signs of functional recovery and animals without recovery. Prior to ischemia the water content of the gray matter was 81.1 plus or minus 0.3% (mean plus or minus S.D.) and of the white matter 68.9 plus or minus 0.8%. The sodium-potassium ratio in the gray matter was 0.43 plus or minus 0.02 and in the white matter 0.62 plus or minus 0.06. During one hour's ischemia brain water did not change significantly, but the differences in the sodium-potassium ratio in white and gray matter were reduced. Blood recirculation of the brain after ischemia caused a considerable increase in brain water content and a shift in the sodium-potassium ratio up to 1.0. Calculated brain swelling was maximal after 45 min when it reached 11.1% of the total brain volume in an animal with recovery and 12.2% in another one without recovery. In animals with signs of functional recovery brain swelling rapidly diminished, followed by a more gradual normalization of brain electrolytes within 24 h. In animals without functional recovery electrolyte shifts were irreversible or even progressed further. It is concluded that brain swelling and electrolyte derangements following one hour's cerebral ischemia are fully reversible when signs of functional recovery appear and brain metabolism returns.", "contents": "Resuscitation of the monkey brain after one hour's complete ischemia. II. Brain water and electrolytes. Adult normothermic rhesus monkeys were submitted to one hour's complete cerebral ischemia, followed by periods of blood recirculation varying from 45 min to 24 h. The functional impact of ischemia and the subsequent recovery was monitored by electrophysiological recording and a distinction was made between animals with signs of functional recovery and animals without recovery. Prior to ischemia the water content of the gray matter was 81.1 plus or minus 0.3% (mean plus or minus S.D.) and of the white matter 68.9 plus or minus 0.8%. The sodium-potassium ratio in the gray matter was 0.43 plus or minus 0.02 and in the white matter 0.62 plus or minus 0.06. During one hour's ischemia brain water did not change significantly, but the differences in the sodium-potassium ratio in white and gray matter were reduced. Blood recirculation of the brain after ischemia caused a considerable increase in brain water content and a shift in the sodium-potassium ratio up to 1.0. Calculated brain swelling was maximal after 45 min when it reached 11.1% of the total brain volume in an animal with recovery and 12.2% in another one without recovery. In animals with signs of functional recovery brain swelling rapidly diminished, followed by a more gradual normalization of brain electrolytes within 24 h. In animals without functional recovery electrolyte shifts were irreversible or even progressed further. It is concluded that brain swelling and electrolyte derangements following one hour's cerebral ischemia are fully reversible when signs of functional recovery appear and brain metabolism returns."} {"id": "PMID:162847", "title": "Wilms' tumour: treatment of 113 patients from 1960 to 1971.", "content": "The crude 5-year survival rate among children with Wilms' tumour increased from 54% for those diagnosed from 1960 to 1965 to 81% for the period 1966 to 1971. This resulted from an increased ability to cure metastatic disease and, to a lesser extent, to an increased ability to prevent relapse. It is proposed that, after resection and postoperative irradiation, maintained combination chemotherapy with actinomycin D and vincristine should be used electively to prevent relapse, but that this use should also be selective in order that overall morbidity be minimized. Of urgent priority, therefore, is improved delineation of present-day prognostic factors in children with Wilms' tumour.", "contents": "Wilms' tumour: treatment of 113 patients from 1960 to 1971. The crude 5-year survival rate among children with Wilms' tumour increased from 54% for those diagnosed from 1960 to 1965 to 81% for the period 1966 to 1971. This resulted from an increased ability to cure metastatic disease and, to a lesser extent, to an increased ability to prevent relapse. It is proposed that, after resection and postoperative irradiation, maintained combination chemotherapy with actinomycin D and vincristine should be used electively to prevent relapse, but that this use should also be selective in order that overall morbidity be minimized. Of urgent priority, therefore, is improved delineation of present-day prognostic factors in children with Wilms' tumour."} {"id": "PMID:162849", "title": "Combined modality therapy for intracranial tumors.", "content": "Three types of tumor (supratentorial astrocytoma, medulloblastoma, and craniopharyngioma), each requiring a fundamentally different therapeutic approach, will be used to illustrate the principles and practice of combined treatment in this field. The role of radiotherapy and ways of enhancing the effect of irradiation will be considered. Attention will be given to adjuvant chemotherapy and to multiple drug regimes. Reference will be made to an early effort at immunotherapy following the initial reduction of tumor cell load by surgery and irradiation.", "contents": "Combined modality therapy for intracranial tumors. Three types of tumor (supratentorial astrocytoma, medulloblastoma, and craniopharyngioma), each requiring a fundamentally different therapeutic approach, will be used to illustrate the principles and practice of combined treatment in this field. The role of radiotherapy and ways of enhancing the effect of irradiation will be considered. Attention will be given to adjuvant chemotherapy and to multiple drug regimes. Reference will be made to an early effort at immunotherapy following the initial reduction of tumor cell load by surgery and irradiation."} {"id": "PMID:162850", "title": "Prognostically favorable immunogens of human breast cancer tissue: antigenic similarity to murine mammary tumor virus.", "content": "A leukocyte migration procedure was utilized to test cellular hypersensitivity of breast cancer patients' leukocytes to autologous and homologous breast cancer tissues and to murine milk containing murine mammary tumor virus (MuMTV). The in vitro responsiveness of the leukocytes and the antigenicity of breast cancer tissues were compared with in vivo prognostically favorable lymphoreticuloendothelial (L-RE) responses seen microscopically at the time of mastectomy and with the results of skin window tests of cellular hypersensitivity. The data suggest that immunogens appear in the in situ phase of the disease and provoke prognostically favorable L-RE responses. These immunogens possess antigenic similarity to some component(s) of MuMTV. Progression of the disease is associated with or preceded by a loss of tissue immunogenicity and/or diminished specific cellular hypersensitivity. The findings are pertinent to investigations of human mammary carcinogenesis and immunoprophylaxis.", "contents": "Prognostically favorable immunogens of human breast cancer tissue: antigenic similarity to murine mammary tumor virus. A leukocyte migration procedure was utilized to test cellular hypersensitivity of breast cancer patients' leukocytes to autologous and homologous breast cancer tissues and to murine milk containing murine mammary tumor virus (MuMTV). The in vitro responsiveness of the leukocytes and the antigenicity of breast cancer tissues were compared with in vivo prognostically favorable lymphoreticuloendothelial (L-RE) responses seen microscopically at the time of mastectomy and with the results of skin window tests of cellular hypersensitivity. The data suggest that immunogens appear in the in situ phase of the disease and provoke prognostically favorable L-RE responses. These immunogens possess antigenic similarity to some component(s) of MuMTV. Progression of the disease is associated with or preceded by a loss of tissue immunogenicity and/or diminished specific cellular hypersensitivity. The findings are pertinent to investigations of human mammary carcinogenesis and immunoprophylaxis."} {"id": "PMID:162851", "title": "Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): general considerations and electron microscopic and tissue culture studies.", "content": "Correlated light and electron microscopic study of four fibrous histiocytomas of proven malignancy has confirmed the presence of histiocyte-like and fibroblast-like cells in this tumor. In addition, an undifferentiated cell type, giant cells, xanthomatous cells, and rare cells with morphological characteristics intermediate between those of histiocytes and fibroblasts were seen. \"Nuclear body\" type inclusions were commonly present in both principal cell types in all four cases, as were the somewhat less common cytoplasmic inclusion bodies. Electron microscopic study of a tissue culture of one of these tumors demonstrated only fibroblast-like, histiocyte-like, and xanthomatous cells. The possibility is suggested that both principal cell types in this tumor may derive from the same undifferentiated stem cell.", "contents": "Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): general considerations and electron microscopic and tissue culture studies. Correlated light and electron microscopic study of four fibrous histiocytomas of proven malignancy has confirmed the presence of histiocyte-like and fibroblast-like cells in this tumor. In addition, an undifferentiated cell type, giant cells, xanthomatous cells, and rare cells with morphological characteristics intermediate between those of histiocytes and fibroblasts were seen. \"Nuclear body\" type inclusions were commonly present in both principal cell types in all four cases, as were the somewhat less common cytoplasmic inclusion bodies. Electron microscopic study of a tissue culture of one of these tumors demonstrated only fibroblast-like, histiocyte-like, and xanthomatous cells. The possibility is suggested that both principal cell types in this tumor may derive from the same undifferentiated stem cell."} {"id": "PMID:162852", "title": "Chemodectoma of the vagus nerve. Report of a case with ultrastructural study.", "content": "Light and electron microscopic studies of a chemodectoma of the vagus nerve are presented. Forty-four cases of vagal chemodectoma have been reported to date, but no electronmicroscopic studies have been published. The ultramicroscopic studies showed the presence of clear and dark cells and membrane-bound neurosecretory granules, and the absence of sustentacular cells and nerve endings. Similar findings have been reported in cases of carotid body and glomus jugulare tumors.", "contents": "Chemodectoma of the vagus nerve. Report of a case with ultrastructural study. Light and electron microscopic studies of a chemodectoma of the vagus nerve are presented. Forty-four cases of vagal chemodectoma have been reported to date, but no electronmicroscopic studies have been published. The ultramicroscopic studies showed the presence of clear and dark cells and membrane-bound neurosecretory granules, and the absence of sustentacular cells and nerve endings. Similar findings have been reported in cases of carotid body and glomus jugulare tumors."} {"id": "PMID:162853", "title": "The success and failure of multimodal therapy for cancer in children.", "content": "Achievements, as well as limitation, in combination treatment of childhood malignancies are discussed. Tumor types are grouped according to response (definite, probable, unknown) to combined treatment. Improvements in survival rates have occurred following the addition of chemotherapy to surgery and radiation therapy in children with Wilmes' tumor, and Ewing's and soft tissue sarcoma, probably by suppression of microscopic metastases. So far, advances are not yet apparent following multimodal treatment of neuroblastoma, hepatoma, and ovarian tumors.", "contents": "The success and failure of multimodal therapy for cancer in children. Achievements, as well as limitation, in combination treatment of childhood malignancies are discussed. Tumor types are grouped according to response (definite, probable, unknown) to combined treatment. Improvements in survival rates have occurred following the addition of chemotherapy to surgery and radiation therapy in children with Wilmes' tumor, and Ewing's and soft tissue sarcoma, probably by suppression of microscopic metastases. So far, advances are not yet apparent following multimodal treatment of neuroblastoma, hepatoma, and ovarian tumors."} {"id": "PMID:162854", "title": "Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer.", "content": "In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.", "contents": "Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer. In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade."} {"id": "PMID:162855", "title": "Inhibition of rat liver DNA polymerase by nitrosoureas and isocyanates.", "content": "The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexl-1-nitrosourea, and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea on two nonmitochondrial DNA polymerases (I and II) purified from rat liver and hepatoma were examined. The activity of DNA polymerase I was not altered by treatment with any of the nitrosoureas or the corresponding isocyanates, 2-chloroethyl isocyanate and cyclohexyl isocyanate. Incubation of DNA polymerase II with the nitrosoureas (1 mM) inhibited its enzymatic activity 30 to 45%. DNA polymerase II was inhibited 75 and 90% by 1.mM 2-chloroethyl isocyanate and cyclohexyl isocyanate, respectively. The nitrosoureas appear to exert their inhabitory action on the enzyme (DNA polymerase II) rather than on the DNA template. Pretreatment of the enzyme increased the degree of inhibition by 1 mM nitrosourea (50 to 60% inhibition) or 2-chloroethul isocyanate (greater than 90% inhibition), whereas pretreatment of the DNA template did not enhance the inhibitory effect. The three nitrosoureas are equally effective as inhibitors of DNA polymerase II. 2-Chloroethyl isocyanate and cyclohexyl isocyanate are better inhibitors than are the nitrosoureas. Since further decomposition products of the isocyanates, 2-chloroethylamine and cyclohexylamine, do not inhibit DNA polymerase II, we conclude that the isocyanates, which are decomposition products of the nitrosoureas, are the active inhibitors of the enzyme.", "contents": "Inhibition of rat liver DNA polymerase by nitrosoureas and isocyanates. The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexl-1-nitrosourea, and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea on two nonmitochondrial DNA polymerases (I and II) purified from rat liver and hepatoma were examined. The activity of DNA polymerase I was not altered by treatment with any of the nitrosoureas or the corresponding isocyanates, 2-chloroethyl isocyanate and cyclohexyl isocyanate. Incubation of DNA polymerase II with the nitrosoureas (1 mM) inhibited its enzymatic activity 30 to 45%. DNA polymerase II was inhibited 75 and 90% by 1.mM 2-chloroethyl isocyanate and cyclohexyl isocyanate, respectively. The nitrosoureas appear to exert their inhabitory action on the enzyme (DNA polymerase II) rather than on the DNA template. Pretreatment of the enzyme increased the degree of inhibition by 1 mM nitrosourea (50 to 60% inhibition) or 2-chloroethul isocyanate (greater than 90% inhibition), whereas pretreatment of the DNA template did not enhance the inhibitory effect. The three nitrosoureas are equally effective as inhibitors of DNA polymerase II. 2-Chloroethyl isocyanate and cyclohexyl isocyanate are better inhibitors than are the nitrosoureas. Since further decomposition products of the isocyanates, 2-chloroethylamine and cyclohexylamine, do not inhibit DNA polymerase II, we conclude that the isocyanates, which are decomposition products of the nitrosoureas, are the active inhibitors of the enzyme."} {"id": "PMID:162856", "title": "Vitamin A (retinyl acetate) and benzo(alpha)pyrene-induced respiratory tract carcinogenesis in hamsters fed a commercial diet.", "content": "Male Syrian hamsters fed a commercial diet were given a series of 12 intratracheal instillations of 3 mg benzo (alpha) pyrene adherent to 3 mg Fe2O3 in 0.2 ml 0.15 M NaCl at weekly intervals. After the last instillation, the hamsters were randomly assigned to receive either 100, 1600, or 3300 (later reduced to 2400) mug retinyl acetate per week in divided intragastric doses. Hamsters in the 2400-mug retinyl acetate group had a significantly higher incidence of respiratory tract tumors than those in the group given 100 mug retinyl acetate per week. Liver vitamin A stores increased dramatically in the groups given 1600 and 2400 mug retinyl acetate and corresponded to the administration of retinyl acetate p.o. Serum vitamin A values were not consistently related to retinyl acetate administration or to hepatic stores of vitamin A.", "contents": "Vitamin A (retinyl acetate) and benzo(alpha)pyrene-induced respiratory tract carcinogenesis in hamsters fed a commercial diet. Male Syrian hamsters fed a commercial diet were given a series of 12 intratracheal instillations of 3 mg benzo (alpha) pyrene adherent to 3 mg Fe2O3 in 0.2 ml 0.15 M NaCl at weekly intervals. After the last instillation, the hamsters were randomly assigned to receive either 100, 1600, or 3300 (later reduced to 2400) mug retinyl acetate per week in divided intragastric doses. Hamsters in the 2400-mug retinyl acetate group had a significantly higher incidence of respiratory tract tumors than those in the group given 100 mug retinyl acetate per week. Liver vitamin A stores increased dramatically in the groups given 1600 and 2400 mug retinyl acetate and corresponded to the administration of retinyl acetate p.o. Serum vitamin A values were not consistently related to retinyl acetate administration or to hepatic stores of vitamin A."} {"id": "PMID:162857", "title": "Transplantation of hepatomas induced in the avian liver by MC29 leukosis virus.", "content": "A hepatomatous growth derived from primary liver tumors induced in chickens by i.v. inoculation with MC29 leukosis virus has been established and maintained in the avian host. Hepatoma tissue transplanted into the abdominal cavity in a total of 278 chicks in 35 experiments yielded tumors in 222 animals (80%). The i.m. implantation in 69 birds in 7 experiments resulted in growth in 67 chicks (97%). Tumor tissue introduced inadvertently into the s.c. tissue likewise grew very rapidly. Histological and cytological features of the transplants in all sites showed preservation of the morphological characteristics of the original primary liver tumors through repeated passages. The properties of this first transplantable hepatoma derived from virus-induced primary liver tumors are compared with those of other transplantable hepatomas.", "contents": "Transplantation of hepatomas induced in the avian liver by MC29 leukosis virus. A hepatomatous growth derived from primary liver tumors induced in chickens by i.v. inoculation with MC29 leukosis virus has been established and maintained in the avian host. Hepatoma tissue transplanted into the abdominal cavity in a total of 278 chicks in 35 experiments yielded tumors in 222 animals (80%). The i.m. implantation in 69 birds in 7 experiments resulted in growth in 67 chicks (97%). Tumor tissue introduced inadvertently into the s.c. tissue likewise grew very rapidly. Histological and cytological features of the transplants in all sites showed preservation of the morphological characteristics of the original primary liver tumors through repeated passages. The properties of this first transplantable hepatoma derived from virus-induced primary liver tumors are compared with those of other transplantable hepatomas."} {"id": "PMID:162858", "title": "Uptake, metabolism, and persistence of 3-methylcholanthrene in rat embryo cells infected with murine leukemia virus.", "content": "The uptake and persistence of 3-methylcholanthrene have been followed in both unifected rat embryo tissue culture cells and in cells infected with type C RNA virus. No significant differences in these parameters were observed as a function of viral infection or cell passage level. Moreover, neither binding of 3-methylcholanthrene to nucleic acids or proteins nor carcinogen metabolism were altered by the viral carrier state. Although transformation of rat cells by chemical carcinogens alone has been reported by us and other authors, the low-passage rat embryo cells used in this study will not transform unless cells are carrying exogenous type C RNA virus. We thus suggest that the virus must play a more direct role in the transformation process rather than affecting the ability of the cell to absorb, retain, or metabolize the chemical.", "contents": "Uptake, metabolism, and persistence of 3-methylcholanthrene in rat embryo cells infected with murine leukemia virus. The uptake and persistence of 3-methylcholanthrene have been followed in both unifected rat embryo tissue culture cells and in cells infected with type C RNA virus. No significant differences in these parameters were observed as a function of viral infection or cell passage level. Moreover, neither binding of 3-methylcholanthrene to nucleic acids or proteins nor carcinogen metabolism were altered by the viral carrier state. Although transformation of rat cells by chemical carcinogens alone has been reported by us and other authors, the low-passage rat embryo cells used in this study will not transform unless cells are carrying exogenous type C RNA virus. We thus suggest that the virus must play a more direct role in the transformation process rather than affecting the ability of the cell to absorb, retain, or metabolize the chemical."} {"id": "PMID:162859", "title": "Mechanism of cell entry and toxicity of an affinity- purified lectin from Ricinus communis and its differential effects on normal and virus-transformed fibroblasts.", "content": "An affinity-purified plant lectin from Ricinus communis (RCAII) was shown to exhibit differential toxicity toward SV40-transformed 3T3 fibroblasts grown in vitro. When macromolecular synthesis was examined in SV3T3 and 3T3 cells, RCAII suppressed cell protein synthesis in the transformed line at lower concentrations (1/50 to 1/100) compared to the 3T3 line, and these effects were blocked by the RCAII inhibitors D-galactose or lactose. RNA and DNA synthesis and L-leucine transport were relatively unaffected by RCAII concentrations (greater than 1 mug/ml) that completely suppressed protein synthesis in both cell lines. The RCAII-mediated inhibition of cell protein synthesis required incubation times longer than 60 min, but quantitative cell binding studies with 125-I-RCAII indicated that the lectin binds to maximal levels in approximately 5 to 10 min, even at 4 degrees. During 10-min labeling experiments with 125-I-RCAII (1 mug/ml), it was demonstrated that the cell-bound lectin could be almost quantitatively removed from cells up to an additional 15 min after labeling without subsequent inhibition of protein synthesis. However, longer incubation times (greater than 30 min) after RCAII cell labeling and washing resulted in incomplete removal of cell-bound lectin (less than 20 to 30% of cell-bound lectin could be removed after a 60-min incubation). The longer incubation times (greater than 60 min) also resulted in almost complete inhibition of protein synthesis. Ferritin-conjugated RCAII (ferritin-RCAII) was used to follow the fate of the cell-bound lectin. Ferritin-RCAII bound rapidly (less than 10 min) to SV3T3 cell surfaces and could be blocked from labeling with lactose. After a 10-min incubation at 4 degrees in ferritin-RCAII solutions, the ferritin label was exclusively located at the extracellular surface in a random distribution. After washing and incubation at 37 degrees, the ferritin-RCAII induced clustering of its receptors (15 to 30 min) and eventually induced endocytosis (30 to 60 min). Further incubation (greater than 60 min) resulted in a predominantly intracellular localization of ferritin-RCAII inside endocytotic vesicles and free in the cell cytoplasm. That RCAII acts directly on protein synthesis after cell entry was confirmed with rabbit reticulocyte and mouse Krebs II ascites S30 cell-free protein synthesis system in diameter wit", "contents": "Mechanism of cell entry and toxicity of an affinity- purified lectin from Ricinus communis and its differential effects on normal and virus-transformed fibroblasts. An affinity-purified plant lectin from Ricinus communis (RCAII) was shown to exhibit differential toxicity toward SV40-transformed 3T3 fibroblasts grown in vitro. When macromolecular synthesis was examined in SV3T3 and 3T3 cells, RCAII suppressed cell protein synthesis in the transformed line at lower concentrations (1/50 to 1/100) compared to the 3T3 line, and these effects were blocked by the RCAII inhibitors D-galactose or lactose. RNA and DNA synthesis and L-leucine transport were relatively unaffected by RCAII concentrations (greater than 1 mug/ml) that completely suppressed protein synthesis in both cell lines. The RCAII-mediated inhibition of cell protein synthesis required incubation times longer than 60 min, but quantitative cell binding studies with 125-I-RCAII indicated that the lectin binds to maximal levels in approximately 5 to 10 min, even at 4 degrees. During 10-min labeling experiments with 125-I-RCAII (1 mug/ml), it was demonstrated that the cell-bound lectin could be almost quantitatively removed from cells up to an additional 15 min after labeling without subsequent inhibition of protein synthesis. However, longer incubation times (greater than 30 min) after RCAII cell labeling and washing resulted in incomplete removal of cell-bound lectin (less than 20 to 30% of cell-bound lectin could be removed after a 60-min incubation). The longer incubation times (greater than 60 min) also resulted in almost complete inhibition of protein synthesis. Ferritin-conjugated RCAII (ferritin-RCAII) was used to follow the fate of the cell-bound lectin. Ferritin-RCAII bound rapidly (less than 10 min) to SV3T3 cell surfaces and could be blocked from labeling with lactose. After a 10-min incubation at 4 degrees in ferritin-RCAII solutions, the ferritin label was exclusively located at the extracellular surface in a random distribution. After washing and incubation at 37 degrees, the ferritin-RCAII induced clustering of its receptors (15 to 30 min) and eventually induced endocytosis (30 to 60 min). Further incubation (greater than 60 min) resulted in a predominantly intracellular localization of ferritin-RCAII inside endocytotic vesicles and free in the cell cytoplasm. That RCAII acts directly on protein synthesis after cell entry was confirmed with rabbit reticulocyte and mouse Krebs II ascites S30 cell-free protein synthesis system in diameter wit"} {"id": "PMID:162860", "title": "Carbamyl phosphate synthetases in rat liver neoplasms.", "content": "Isozymes of carbamyl phosphate synthetase (CPS), CPS I, a mitochondrial enzyme found exclusively in liver and involved in urea synthesis, and of CPS II, a soluble cytoplasmic enzyme widely distributed in animal tissues, were assayed in rat liver and in a series of rat liver neoplasms ranging widely in growth rate and degree of differentiation. CPS I was absent from fast-growing, poorly differentiated hepatomas, such as the Novikoff hepatoma and Morris hepatomas 3924A and 9098F, but was present in slow-growing, well- and highly differentiated Morris hepatomas. However, there was no close correlation between the growth rate or degree of differentiation and the CPS I activity. Activity was very high, at levels comparable with normal liver at about 9 UNITS/G, IN SLOW-GROWING, HEPATOMAS 21, 47C, and 28A but was very low in other slow-growing highly differentiated hepatomas 9618A, 66, and 16. CPS II activity was present in normal liver and all hepatomas examined, but with very low activity, of the order of 1% or less of that of CPS I activity, with maximal values at 5 to 70 milliunits/g. Again, there was no clear correlation with growth rate; the activity was lowest in fast-growing, poorly differentiated hepatomas. A striking observation was a marked lowering of CPS I activity in livers of rats bearing large, slow-growing tumors that have high CPS I activity. As the tumors grew larger and the liver CPS I decreased, a relatively constant total CPS I activity was maintained, suggesting the existence of a homeostatic mechanism. The effect was not observed in rats bearing either fast-growing hepatomas or slow-growing hepatomas with low CPS I activity and was not due to some specific nutritional effects of the tumor on the host.", "contents": "Carbamyl phosphate synthetases in rat liver neoplasms. Isozymes of carbamyl phosphate synthetase (CPS), CPS I, a mitochondrial enzyme found exclusively in liver and involved in urea synthesis, and of CPS II, a soluble cytoplasmic enzyme widely distributed in animal tissues, were assayed in rat liver and in a series of rat liver neoplasms ranging widely in growth rate and degree of differentiation. CPS I was absent from fast-growing, poorly differentiated hepatomas, such as the Novikoff hepatoma and Morris hepatomas 3924A and 9098F, but was present in slow-growing, well- and highly differentiated Morris hepatomas. However, there was no close correlation between the growth rate or degree of differentiation and the CPS I activity. Activity was very high, at levels comparable with normal liver at about 9 UNITS/G, IN SLOW-GROWING, HEPATOMAS 21, 47C, and 28A but was very low in other slow-growing highly differentiated hepatomas 9618A, 66, and 16. CPS II activity was present in normal liver and all hepatomas examined, but with very low activity, of the order of 1% or less of that of CPS I activity, with maximal values at 5 to 70 milliunits/g. Again, there was no clear correlation with growth rate; the activity was lowest in fast-growing, poorly differentiated hepatomas. A striking observation was a marked lowering of CPS I activity in livers of rats bearing large, slow-growing tumors that have high CPS I activity. As the tumors grew larger and the liver CPS I decreased, a relatively constant total CPS I activity was maintained, suggesting the existence of a homeostatic mechanism. The effect was not observed in rats bearing either fast-growing hepatomas or slow-growing hepatomas with low CPS I activity and was not due to some specific nutritional effects of the tumor on the host."} {"id": "PMID:162861", "title": "Specific increase in polyamine levels in chick embryo cells transformed by Rous sarcoma virus.", "content": "Chick embryo fibroblasts and chorioallantoic membranes of chick embryos infected with oncogenic or nononcogenic viruses were analyzed for polyamines. Nononcogenic viruses (influenze, Newcastle disease, or vaccinia virus) had no effect on the polyamine content of chorioallantoic membranes. Transformation of chorioallantoic membranes by a wild-type or temperature-sensitive mutant strain of Rous sarcoma virus under permissive conditions (37 degrees) caused a 2- to 4-fold increase in cellular spermidine and putrescine content. Only putrescine accumulated in chick embryo fibroblasts transformed by Rous sarcoma virus at 37 degrees. At the nonpermissive temperature (42 degrees), the temperature-sensitive mutant, unlike the wild-type strain, did not alter cellular morphology or polyamine content.", "contents": "Specific increase in polyamine levels in chick embryo cells transformed by Rous sarcoma virus. Chick embryo fibroblasts and chorioallantoic membranes of chick embryos infected with oncogenic or nononcogenic viruses were analyzed for polyamines. Nononcogenic viruses (influenze, Newcastle disease, or vaccinia virus) had no effect on the polyamine content of chorioallantoic membranes. Transformation of chorioallantoic membranes by a wild-type or temperature-sensitive mutant strain of Rous sarcoma virus under permissive conditions (37 degrees) caused a 2- to 4-fold increase in cellular spermidine and putrescine content. Only putrescine accumulated in chick embryo fibroblasts transformed by Rous sarcoma virus at 37 degrees. At the nonpermissive temperature (42 degrees), the temperature-sensitive mutant, unlike the wild-type strain, did not alter cellular morphology or polyamine content."} {"id": "PMID:162862", "title": "Alterations of enzymes associated with plasma membranes and cellular organelles during infection of CV-1 cells with Yaba tumor poxvirus.", "content": "The formation of cellular aggregates (foci) in CV-1 cells following infection with Yaba tumor poxvirus is dependent upon cell passage level, temperatue of incubation, and calcium concentration in the medium. Resistance of older cells can be reversed by maintaining calcium at 0.1 mM or by adding cortisone acetate (1 mug/ml), hydrocortisone, or estradiol-17beta to the cultures. In susceptible cells, foci formation was inhibited slightly by methyltestosterone and inhibited completely by dexamethasone, aldosterone and progesterone. Activities and patterns of enzymes associated with cytoplasmic membranes (alkaline phosphatase, mononucleotidase, and Na+-K+-adenosine triphosphatase) and lysosomes (beta-glucuronidase and acid phosphatase) of the younger susceptible and the older resistant CV-1 cells differed. These differences apparently occurred in concert with phenotypic changes in the membranes that reduced the mobility of older resistant cells. In susceptible culture, unifected cells migrated to the infected cell and participated in foci formation. Reduction of the calcium content to 0.1 mM apparently removed some of the constraints on mobility of the resistant cells. Although the hormones may have had a similar effect, the changes in enzyme patterns indicated basic alterations in protein synthesis. The development of resistance to foci formation occurred between the 45th and 50th passage level. Hormonal reversal of this resistance resulted in enzyme profiles that reflected the pattern of young susceptible cells.", "contents": "Alterations of enzymes associated with plasma membranes and cellular organelles during infection of CV-1 cells with Yaba tumor poxvirus. The formation of cellular aggregates (foci) in CV-1 cells following infection with Yaba tumor poxvirus is dependent upon cell passage level, temperatue of incubation, and calcium concentration in the medium. Resistance of older cells can be reversed by maintaining calcium at 0.1 mM or by adding cortisone acetate (1 mug/ml), hydrocortisone, or estradiol-17beta to the cultures. In susceptible cells, foci formation was inhibited slightly by methyltestosterone and inhibited completely by dexamethasone, aldosterone and progesterone. Activities and patterns of enzymes associated with cytoplasmic membranes (alkaline phosphatase, mononucleotidase, and Na+-K+-adenosine triphosphatase) and lysosomes (beta-glucuronidase and acid phosphatase) of the younger susceptible and the older resistant CV-1 cells differed. These differences apparently occurred in concert with phenotypic changes in the membranes that reduced the mobility of older resistant cells. In susceptible culture, unifected cells migrated to the infected cell and participated in foci formation. Reduction of the calcium content to 0.1 mM apparently removed some of the constraints on mobility of the resistant cells. Although the hormones may have had a similar effect, the changes in enzyme patterns indicated basic alterations in protein synthesis. The development of resistance to foci formation occurred between the 45th and 50th passage level. Hormonal reversal of this resistance resulted in enzyme profiles that reflected the pattern of young susceptible cells."} {"id": "PMID:162863", "title": "Development of concomitant immunity in mice bearing the weakly immunogenic line 1 lung carcinoma.", "content": "The interaction between line 1 carcinomas growing s.c. and their spontaneous (or artificial) metastases has been studied in syngeneic BALB/c mice. In contrast to typical murine tumor systems, concomitant immunity, or the ability of primary tumors to suppress the growth of metastases, develops very slowly in this system, such that the metastases that are shed within the first week of tumor growth survive and ultimately prove lethal to the host. The rate of development of concomitant immunity can be accelerated by increasing the hosts' tumor burden or decelerated by exposure of the hosts to X-rays prior to tumor transplant. This cancer system offers, therefore, an excellent model for the therapy of metastases that cannot be obtained with typical murine tumors.", "contents": "Development of concomitant immunity in mice bearing the weakly immunogenic line 1 lung carcinoma. The interaction between line 1 carcinomas growing s.c. and their spontaneous (or artificial) metastases has been studied in syngeneic BALB/c mice. In contrast to typical murine tumor systems, concomitant immunity, or the ability of primary tumors to suppress the growth of metastases, develops very slowly in this system, such that the metastases that are shed within the first week of tumor growth survive and ultimately prove lethal to the host. The rate of development of concomitant immunity can be accelerated by increasing the hosts' tumor burden or decelerated by exposure of the hosts to X-rays prior to tumor transplant. This cancer system offers, therefore, an excellent model for the therapy of metastases that cannot be obtained with typical murine tumors."} {"id": "PMID:162864", "title": "Growth and structural properties of epithelial cell cultures established from normal rat liver and chemically induced hepatomas.", "content": "Epithelial cultures established from adult rat liver and from rat hepatomas induced in vivo with aromatic amine carcinogens have been compared by light and electron microscopy and by growth properties in liquid medium and in agar. The morphology and growth patterns of all of these cultures indicate that they have characteristics of epithelial rather than fibroblast cells. The criteria generally used to score for transformation of fibroblasts were not satisfactory for distinguishing normal epithelial cells from hepatoma cells in culture. Growth in agar, however, provides a simple and objective method of scoring for transformed epithelial cells, because only the tumorigenic cells grow in agar. Since none of the normal cultures had hydrocortisone-inducible tryosine aminotransferase, we lack definitive evidence that they are derived from liver parenchymal cells. The outstanding feature in the ultrastructure of the hepatoma cells in culture was the presence of type A and C viral particles. Whereas five hepatoma cultures and a spontaneously transformed normal liver cell line were positive for these particles, five independently isolated cell cultures from normal adult rat liver were negative. Evidence is presented that the viral particles seen in hepatoma cultures are due to activation of latent viruses rather than to in vitro contamination. The possible significance of these particles in hepatocarcinogenesis is discussed.", "contents": "Growth and structural properties of epithelial cell cultures established from normal rat liver and chemically induced hepatomas. Epithelial cultures established from adult rat liver and from rat hepatomas induced in vivo with aromatic amine carcinogens have been compared by light and electron microscopy and by growth properties in liquid medium and in agar. The morphology and growth patterns of all of these cultures indicate that they have characteristics of epithelial rather than fibroblast cells. The criteria generally used to score for transformation of fibroblasts were not satisfactory for distinguishing normal epithelial cells from hepatoma cells in culture. Growth in agar, however, provides a simple and objective method of scoring for transformed epithelial cells, because only the tumorigenic cells grow in agar. Since none of the normal cultures had hydrocortisone-inducible tryosine aminotransferase, we lack definitive evidence that they are derived from liver parenchymal cells. The outstanding feature in the ultrastructure of the hepatoma cells in culture was the presence of type A and C viral particles. Whereas five hepatoma cultures and a spontaneously transformed normal liver cell line were positive for these particles, five independently isolated cell cultures from normal adult rat liver were negative. Evidence is presented that the viral particles seen in hepatoma cultures are due to activation of latent viruses rather than to in vitro contamination. The possible significance of these particles in hepatocarcinogenesis is discussed."} {"id": "PMID:162865", "title": "Junctional specialization in estrogen-induced renal adenocarcinomas of the golden hamster.", "content": "Estrogen-dependent renal adenocarcinoma and normal proximal tubules of the hamster kidney exhibit junctional differences. Although both cell types possess gap junctions, the neoplastic cells have in addition a cytoplasmic configuration of gap-junctional membrane (annular nexuses) not found in the kidneys of untreated or estrogenized hamsters or in the nontumorous kidney adjacent to the adenocarcinoma. The presence of these unique structures in the renal tumor and its abdominal metastases was demonstrated by electron microscopy with the use of lanthanum impregnation. A possible correlation between these structures and the estrogen sensitivity of the kidney neoplasm is made.", "contents": "Junctional specialization in estrogen-induced renal adenocarcinomas of the golden hamster. Estrogen-dependent renal adenocarcinoma and normal proximal tubules of the hamster kidney exhibit junctional differences. Although both cell types possess gap junctions, the neoplastic cells have in addition a cytoplasmic configuration of gap-junctional membrane (annular nexuses) not found in the kidneys of untreated or estrogenized hamsters or in the nontumorous kidney adjacent to the adenocarcinoma. The presence of these unique structures in the renal tumor and its abdominal metastases was demonstrated by electron microscopy with the use of lanthanum impregnation. A possible correlation between these structures and the estrogen sensitivity of the kidney neoplasm is made."} {"id": "PMID:162866", "title": "Autoradiographic localization of glycoprotein in human breast cancer cells maintained in organ culture after incubation with (3H)fucose or (3H)glucosamine.", "content": "Explants of nine infiltrating duct carcinomas of the human female breast, maintained in organ culture, were exposed to the glycoprotein precursors, L-[3H]furcose and [3H]glucosamine, in order to determine the cellular distribution of newly synthesized glycoprotein as revealed by autoradiography with the light and electron microscopes. Explants were incubated with a single isotope for 2 hr, at which time some of the labeled explants were removed for autoradiographic analysis while the rest were transferred to nonradioactive medium for an additional 24 hr. After exposure to label for 24 hr, autoradiography with each isotope was similar and showed strong reactions over most tumor cells. The reactions were due to clumps of silver grains over intracytoplasmic lumina within single tumor cells and silver grains over Golgi saccules, cytoplasmic vesicles, lysosome-like bodies, lateral and basal plasma membranes, and microvilli. Extracellular ductular structures were also heavily labeled. At the later sampling time, Golgi saccules often showed a reduced reaction while the reactions over other organelles and intracellular and extracellular ductular structures remained strong. The observations suggest that in our in vitro system the tumor cells are metabolically active and complete the synthesis of the carbohydrate side chains of glycoproteins within the Golgi apparatus. From there, some of the newly synthesized glycoprotein appears to migrate to plasma membranes and lysosome-like bodies. Furthermore, our data support the notion that many duct carcinomas of the breast exhibit secretory activity by showing that some newly synthesized glycoprotein also appears to become products that are secreted into intracellular and extracellular ductular structures.", "contents": "Autoradiographic localization of glycoprotein in human breast cancer cells maintained in organ culture after incubation with (3H)fucose or (3H)glucosamine. Explants of nine infiltrating duct carcinomas of the human female breast, maintained in organ culture, were exposed to the glycoprotein precursors, L-[3H]furcose and [3H]glucosamine, in order to determine the cellular distribution of newly synthesized glycoprotein as revealed by autoradiography with the light and electron microscopes. Explants were incubated with a single isotope for 2 hr, at which time some of the labeled explants were removed for autoradiographic analysis while the rest were transferred to nonradioactive medium for an additional 24 hr. After exposure to label for 24 hr, autoradiography with each isotope was similar and showed strong reactions over most tumor cells. The reactions were due to clumps of silver grains over intracytoplasmic lumina within single tumor cells and silver grains over Golgi saccules, cytoplasmic vesicles, lysosome-like bodies, lateral and basal plasma membranes, and microvilli. Extracellular ductular structures were also heavily labeled. At the later sampling time, Golgi saccules often showed a reduced reaction while the reactions over other organelles and intracellular and extracellular ductular structures remained strong. The observations suggest that in our in vitro system the tumor cells are metabolically active and complete the synthesis of the carbohydrate side chains of glycoproteins within the Golgi apparatus. From there, some of the newly synthesized glycoprotein appears to migrate to plasma membranes and lysosome-like bodies. Furthermore, our data support the notion that many duct carcinomas of the breast exhibit secretory activity by showing that some newly synthesized glycoprotein also appears to become products that are secreted into intracellular and extracellular ductular structures."} {"id": "PMID:162867", "title": "Effect of neurotransmitters, Guanosine triphosphate, and divalent ions on the regulation of adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells.", "content": "The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of \"\"differentiated\" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE1 and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3:5-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP protentiated the PGE1 effect in differentiated concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of Km and Vmax of neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE1 stimulated enzyme activity to GTP increase in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells.", "contents": "Effect of neurotransmitters, Guanosine triphosphate, and divalent ions on the regulation of adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells. The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of \"\"differentiated\" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE1 and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3:5-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP protentiated the PGE1 effect in differentiated concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of Km and Vmax of neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE1 stimulated enzyme activity to GTP increase in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells."} {"id": "PMID:162868", "title": "Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats.", "content": "The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of azoxymethane and a large dose of 1,2-dimethylhydrazine was studied using germ-free and conventional female Fischer rats. Injection s. c. of 1,2-dimethylhydrazine-induced tumors of the ear duct, kidney, and small intestine of conventional rats but none in germ-free animals. Only 20% germ-free rats showed 1,2-dimethylhydrazine-induced colonic tumors, whereas 93% of conventional rats developed multiple colonic tumors. Intrarectal instillation of azoxymethane appreciably increased the multiplicity of colonic tumors in germ-free rats and in gnotobiotic rats contaminated with Clostridium perfringens, as compared to conventional controls. None of the germ-free rats showed ear duct tumors. The incidence of kidney tumors was lower in germ-free rats than in other groups. It is concluded than the intestinal microbial populations alter the effect of carcinogens in the large intestine.", "contents": "Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of azoxymethane and a large dose of 1,2-dimethylhydrazine was studied using germ-free and conventional female Fischer rats. Injection s. c. of 1,2-dimethylhydrazine-induced tumors of the ear duct, kidney, and small intestine of conventional rats but none in germ-free animals. Only 20% germ-free rats showed 1,2-dimethylhydrazine-induced colonic tumors, whereas 93% of conventional rats developed multiple colonic tumors. Intrarectal instillation of azoxymethane appreciably increased the multiplicity of colonic tumors in germ-free rats and in gnotobiotic rats contaminated with Clostridium perfringens, as compared to conventional controls. None of the germ-free rats showed ear duct tumors. The incidence of kidney tumors was lower in germ-free rats than in other groups. It is concluded than the intestinal microbial populations alter the effect of carcinogens in the large intestine."} {"id": "PMID:162869", "title": "Glomerular immune complex deposits associated with mouse mammary tumor.", "content": "Adult Paris R-III mice with localized mamary tumors were found to have subendothelial glomerular immune complex deposits by electron microscopy and immunofluorescence. In addition to IgG adn B-1-C, the glomeruli contained antigenic material that reacted with an antiserum to mouse mamary tumor virus. These findings support the hypothesis that many animals with congenitally or neonatally induced virus-related tumors are not immunologically tolerant to the oncogenic virus.", "contents": "Glomerular immune complex deposits associated with mouse mammary tumor. Adult Paris R-III mice with localized mamary tumors were found to have subendothelial glomerular immune complex deposits by electron microscopy and immunofluorescence. In addition to IgG adn B-1-C, the glomeruli contained antigenic material that reacted with an antiserum to mouse mamary tumor virus. These findings support the hypothesis that many animals with congenitally or neonatally induced virus-related tumors are not immunologically tolerant to the oncogenic virus."} {"id": "PMID:162870", "title": "A carcinofetal antigen located on the membrane of cells from rat intestinal carcinoma in culture.", "content": "Heteroantisera were produced in rabbits by immunization with cultivated cells from rat intestinal carcinomas. The sera were made specific by in vivo absorption in syngeneic rats. On immunofluorescence, these sera recognized a membrane-associated antigen common to five different intestinal carcinomas and to fetal intestine. The antigen was not detected in noncancerous adult intestine, nonintestinal fetal tissues, or three nonintestinal tumor cell lines.", "contents": "A carcinofetal antigen located on the membrane of cells from rat intestinal carcinoma in culture. Heteroantisera were produced in rabbits by immunization with cultivated cells from rat intestinal carcinomas. The sera were made specific by in vivo absorption in syngeneic rats. On immunofluorescence, these sera recognized a membrane-associated antigen common to five different intestinal carcinomas and to fetal intestine. The antigen was not detected in noncancerous adult intestine, nonintestinal fetal tissues, or three nonintestinal tumor cell lines."} {"id": "PMID:162871", "title": "Characteristics of rat carcinoma in culture.", "content": "Rat chloroma cells have been propagated in permanent suspension cultures and are grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum and 2.5% horse serum. Several lines have been established; the one of longest duration, Mia C51, has been maintained for over 18 months and has undergone over 100 transfers. Mia C51 cells have a doubling time of 12 hr and maintain many of the properties of the parent tumor, including the characteristic greenish color with high myeloperoxidase activity, an an aneuploid chromosomal pattern, and intact tumorigenicity. They will uniformly produce greenish chloroma tumors when injected into newborn rats. Electron microscopic examination of chloroma tumors and the cultured cells derived from them reveal the presence of extracellular mature and immature type C virus particles morphologically typical of oncornaviruses. Chloroma cells obtained from tumors that lost their alkaline phosphatase activity after repeated transfer regain full activity in culture. Studies using the antigen-antibody crossed electrophoresis indicate that the loss of alkaline phosphatase activity represents a true decrease in alkaline phosphatase protein, which is restored under culture conditions. The availability of a permanent chloroma cell line in culture that maintains the biological properties of the parent tumor provides a useful model for the study of myeloid leukemia.", "contents": "Characteristics of rat carcinoma in culture. Rat chloroma cells have been propagated in permanent suspension cultures and are grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum and 2.5% horse serum. Several lines have been established; the one of longest duration, Mia C51, has been maintained for over 18 months and has undergone over 100 transfers. Mia C51 cells have a doubling time of 12 hr and maintain many of the properties of the parent tumor, including the characteristic greenish color with high myeloperoxidase activity, an an aneuploid chromosomal pattern, and intact tumorigenicity. They will uniformly produce greenish chloroma tumors when injected into newborn rats. Electron microscopic examination of chloroma tumors and the cultured cells derived from them reveal the presence of extracellular mature and immature type C virus particles morphologically typical of oncornaviruses. Chloroma cells obtained from tumors that lost their alkaline phosphatase activity after repeated transfer regain full activity in culture. Studies using the antigen-antibody crossed electrophoresis indicate that the loss of alkaline phosphatase activity represents a true decrease in alkaline phosphatase protein, which is restored under culture conditions. The availability of a permanent chloroma cell line in culture that maintains the biological properties of the parent tumor provides a useful model for the study of myeloid leukemia."} {"id": "PMID:162872", "title": "Induction of permanently proliferating human lymphoblastoid lines by N-methyl-N'-nitro-N-nitrosoguanidine.", "content": "N-Methyl-N'-nitro-N-nitrosoguanidine treatment of human peripheral blood mononuclear cells increases the frequency of lymphocyte transformation into permanently proliferating lines. The transformation is dependent on the dose of N-methyl-N-7-nitro-N-nitrosoguanidine and does not occur in the presence of autologous human serum. Thirty-eight of the forty-two established lines resulting fron N-methyl-N'-nitro-N-nitrosoguanidine treatment produced detectable Epstein-Barr virus antigens.", "contents": "Induction of permanently proliferating human lymphoblastoid lines by N-methyl-N'-nitro-N-nitrosoguanidine. N-Methyl-N'-nitro-N-nitrosoguanidine treatment of human peripheral blood mononuclear cells increases the frequency of lymphocyte transformation into permanently proliferating lines. The transformation is dependent on the dose of N-methyl-N-7-nitro-N-nitrosoguanidine and does not occur in the presence of autologous human serum. Thirty-eight of the forty-two established lines resulting fron N-methyl-N'-nitro-N-nitrosoguanidine treatment produced detectable Epstein-Barr virus antigens."} {"id": "PMID:162873", "title": "Characteristics of mammary tumor cultures from four mouse strains infected with mammary tumor virus.", "content": "The morphology and production of oncornaviruses in primary cell and explant mammary adenocarcinoma cultures derived from C3Hf, BALB/cNIV, BALB/cfC3H, and C3H mice were characterized. Cultures from the four mouse strains were morphologically similar; they were all epithelial and formed hemicysts and mounds. However, the numbers of cells containing mammary tumor virus (MTV) antigens and the production of cell-free MTV varied greatly among the established cultures. The percentages of MTV-positive cells in the cultures correlated with detection of cell-free MRV; immunodiffusion assays of virions from C3Hf and BALB/cNIV cultures were consistently negative for MTV antigens, whereas virions from BALB/cfC3H and C3H cultures were always positive. Synthesis of murine leukemia virus group-specific, soluble antigens was always observed in C3Hf, BALB/cNIV, and C3H cultures but only rarely observed in BALB/cfC3H cultures.", "contents": "Characteristics of mammary tumor cultures from four mouse strains infected with mammary tumor virus. The morphology and production of oncornaviruses in primary cell and explant mammary adenocarcinoma cultures derived from C3Hf, BALB/cNIV, BALB/cfC3H, and C3H mice were characterized. Cultures from the four mouse strains were morphologically similar; they were all epithelial and formed hemicysts and mounds. However, the numbers of cells containing mammary tumor virus (MTV) antigens and the production of cell-free MTV varied greatly among the established cultures. The percentages of MTV-positive cells in the cultures correlated with detection of cell-free MRV; immunodiffusion assays of virions from C3Hf and BALB/cNIV cultures were consistently negative for MTV antigens, whereas virions from BALB/cfC3H and C3H cultures were always positive. Synthesis of murine leukemia virus group-specific, soluble antigens was always observed in C3Hf, BALB/cNIV, and C3H cultures but only rarely observed in BALB/cfC3H cultures."} {"id": "PMID:162874", "title": "Mechanism of natural resistance to N6-(delta2-isopentenyl)adenosine in cultured cells.", "content": "Twenty-one cell lines (six human lines, and nine mouse lines) were compared with respect to inhibition of growth by N-6-(delta-2-isopentenyl)adenosine (IPAR). Six of these, mouse Sarcoma 180, Ehrilich ascites carcinoma, mammary adenocarconoma (TA3), leukemia L1210, mouse kidney, and canine kidney cells, differed by up to 16-fold with respect to their sensitivity and were chosen for further study. One factor contributing to the resistance was a slower formation of intracellular 5-monophosphate of IPAR (IPAMP) due to reduced adenosine kinase activity. Because of this slower formation of IPAMP in the resistant cells, a higher extracellular IPAR was required for the maintenance of equal intracellular IPAMP levels. Regardless of the degree of resistance, the rate of decay of intracellular IPAMP was similar and very rapid, with a half-life of 37 plus or minus 5 min. In the sensitive cells IPAMP was cleaved back to IPAR, while in the resistant cells IPAR was cleaved further to the free base, N-6-(delta-2-isopentenyl)adenine (IPA), which accumulated in the medium. The rate of formation of IPA constitutes an irreversible inactivation of IPAR, because IPA is not converted back to IPAMP and is not growth inhibitory. In one of the resistant cells (mouse kidney) the inactivation was so rapid that in 1 hr 25% of the extracellular (30 muM) IPAR was converted to IPA.", "contents": "Mechanism of natural resistance to N6-(delta2-isopentenyl)adenosine in cultured cells. Twenty-one cell lines (six human lines, and nine mouse lines) were compared with respect to inhibition of growth by N-6-(delta-2-isopentenyl)adenosine (IPAR). Six of these, mouse Sarcoma 180, Ehrilich ascites carcinoma, mammary adenocarconoma (TA3), leukemia L1210, mouse kidney, and canine kidney cells, differed by up to 16-fold with respect to their sensitivity and were chosen for further study. One factor contributing to the resistance was a slower formation of intracellular 5-monophosphate of IPAR (IPAMP) due to reduced adenosine kinase activity. Because of this slower formation of IPAMP in the resistant cells, a higher extracellular IPAR was required for the maintenance of equal intracellular IPAMP levels. Regardless of the degree of resistance, the rate of decay of intracellular IPAMP was similar and very rapid, with a half-life of 37 plus or minus 5 min. In the sensitive cells IPAMP was cleaved back to IPAR, while in the resistant cells IPAR was cleaved further to the free base, N-6-(delta-2-isopentenyl)adenine (IPA), which accumulated in the medium. The rate of formation of IPA constitutes an irreversible inactivation of IPAR, because IPA is not converted back to IPAMP and is not growth inhibitory. In one of the resistant cells (mouse kidney) the inactivation was so rapid that in 1 hr 25% of the extracellular (30 muM) IPAR was converted to IPA."} {"id": "PMID:162875", "title": "Subcellular distribution of the enzymes related to the cellular action of vasopressin in renal medulla.", "content": "Subcellular distribution of the enzymes related to the cellular action of antidiuretic hormone was studied in bovine renal medulla. The highest activity of vasopressin-stimulated adenylate cyclase was found in plasma membranes. The basal activity increased two times above homogenate while vasopressin-stimulated and NaF-stimulated activities both increased five times. Adenylate cyclase activity was present also in other particulate fractions, but it was not significantly stimulated by vasopressin. Cyclic AMP phosphodiesterase was predominantly located in the cytosol when assayed with 0.5 mM cyclic AMP or with 5 muM cyclic AMP. However, with the latter concentration of cyclic AMP more activity remained associated with the particulate fractions and was more inhibited by theophylline. The highest cyclic AMP-stimulated protein kinase activity occurred in the cytosol. Protein kinase activity present in other subcellular fractions was not markedly stimulated by cyclic AMP. Protein phosphatase activity was highest in cytosol when assayed using 32P-histones, 32P-plasma membrane proteins, and 32P-cytoslic proteins. The activity was unaffected by 10-6M to 10-4M cyclic AMP or cyclic GMP. The activity was completely inhibited by 10mM ZnSO4 and 10mM CuSO4; 10mM NaF inhibited the activity by approximately 14%. The enzymes related to the cellular action of vasopressin are predominatly localized in the cytosol except for the vasopressin-sensitive adenylate cyclase which is plasma membrane bound. To mediate the effect of antidiuretic hormone and act on the luminal plasma membrane these soluble enzymes and their substrates should be compartmentalized, possibly by a system of cytoplasmic microtubules.", "contents": "Subcellular distribution of the enzymes related to the cellular action of vasopressin in renal medulla. Subcellular distribution of the enzymes related to the cellular action of antidiuretic hormone was studied in bovine renal medulla. The highest activity of vasopressin-stimulated adenylate cyclase was found in plasma membranes. The basal activity increased two times above homogenate while vasopressin-stimulated and NaF-stimulated activities both increased five times. Adenylate cyclase activity was present also in other particulate fractions, but it was not significantly stimulated by vasopressin. Cyclic AMP phosphodiesterase was predominantly located in the cytosol when assayed with 0.5 mM cyclic AMP or with 5 muM cyclic AMP. However, with the latter concentration of cyclic AMP more activity remained associated with the particulate fractions and was more inhibited by theophylline. The highest cyclic AMP-stimulated protein kinase activity occurred in the cytosol. Protein kinase activity present in other subcellular fractions was not markedly stimulated by cyclic AMP. Protein phosphatase activity was highest in cytosol when assayed using 32P-histones, 32P-plasma membrane proteins, and 32P-cytoslic proteins. The activity was unaffected by 10-6M to 10-4M cyclic AMP or cyclic GMP. The activity was completely inhibited by 10mM ZnSO4 and 10mM CuSO4; 10mM NaF inhibited the activity by approximately 14%. The enzymes related to the cellular action of vasopressin are predominatly localized in the cytosol except for the vasopressin-sensitive adenylate cyclase which is plasma membrane bound. To mediate the effect of antidiuretic hormone and act on the luminal plasma membrane these soluble enzymes and their substrates should be compartmentalized, possibly by a system of cytoplasmic microtubules."} {"id": "PMID:162876", "title": "Estrogen-induced uterine responses and growth: relationship to receptor estrogen binding by uterine nuclei.", "content": "The relationship between estrogen receptor(R) binding by uterine nuclei and uterotrophic responses was examined. Immature rats received a single injection of estradiol (E2) or estriol (E3) and the following parameters were measured: accumulation and retention of the estrogen receptor by the nuceus of uterine cells; incorporation of 14C-glucose into CO2 lipid, protein and RNA; RNA polymerase activity; water imbibition and increased dry weight. E2 and E3 were of equal potency with regard to the rapid accumulation of R by the nucleus but differed with respect to long term retention of R. The concentrations of nuclear RE2 and RE3 complexes were equivalent between 1 and 3 hr after estrogen injection; however, by 6 hr RE2 remained significantly elevated while RE3 levels had fallen to control values. E2 and E3 were also of equal potency with respect to the stimulation of enhanced glucose utilization, water imbibition, the incorporation of 14C-glucose into lipid, protein and RNA 3 hours following an injection of the hormone. Likewise the activity of RNA polymerase was equally stimulated by E2 and E3 3 hr after injection. Thus all early uterotropic responses (0-3 hrs) that were measured were equally stimulated by E2 and E3. However, E3 failed to stimulate true uterine growth (increase dry weight 24 hr after injection), whereas E2 produced a significant stimulation of true uterine growth. These data suggest that the RE complex is capable of stimulating early uterotrohic events regardless of which estrogen is present; however, in order to produce true uterine growth the RE complex must be retained in the nucleus for long periods of time. This proposal was tested by the administration of repetitive injections of E3. This treatment resulted in an increase in dry weight that was equivalent to the growth that was produced by repetitive injections of E2. These results demonstrate that E2 and E3 elicit early uterotrophic responses with equal facility following a single injection but that only E2 causes true uterine growth. The ability of E2 to stimulate true uterine growth appears to be related to the time of residence of the RE complex in the nucleus.", "contents": "Estrogen-induced uterine responses and growth: relationship to receptor estrogen binding by uterine nuclei. The relationship between estrogen receptor(R) binding by uterine nuclei and uterotrophic responses was examined. Immature rats received a single injection of estradiol (E2) or estriol (E3) and the following parameters were measured: accumulation and retention of the estrogen receptor by the nuceus of uterine cells; incorporation of 14C-glucose into CO2 lipid, protein and RNA; RNA polymerase activity; water imbibition and increased dry weight. E2 and E3 were of equal potency with regard to the rapid accumulation of R by the nucleus but differed with respect to long term retention of R. The concentrations of nuclear RE2 and RE3 complexes were equivalent between 1 and 3 hr after estrogen injection; however, by 6 hr RE2 remained significantly elevated while RE3 levels had fallen to control values. E2 and E3 were also of equal potency with respect to the stimulation of enhanced glucose utilization, water imbibition, the incorporation of 14C-glucose into lipid, protein and RNA 3 hours following an injection of the hormone. Likewise the activity of RNA polymerase was equally stimulated by E2 and E3 3 hr after injection. Thus all early uterotropic responses (0-3 hrs) that were measured were equally stimulated by E2 and E3. However, E3 failed to stimulate true uterine growth (increase dry weight 24 hr after injection), whereas E2 produced a significant stimulation of true uterine growth. These data suggest that the RE complex is capable of stimulating early uterotrohic events regardless of which estrogen is present; however, in order to produce true uterine growth the RE complex must be retained in the nucleus for long periods of time. This proposal was tested by the administration of repetitive injections of E3. This treatment resulted in an increase in dry weight that was equivalent to the growth that was produced by repetitive injections of E2. These results demonstrate that E2 and E3 elicit early uterotrophic responses with equal facility following a single injection but that only E2 causes true uterine growth. The ability of E2 to stimulate true uterine growth appears to be related to the time of residence of the RE complex in the nucleus."} {"id": "PMID:162877", "title": "Interaction of amino acids and cyclic AMP on the release of insulin and glucagon by newborn rat pancreas.", "content": "Splenic lobes from the pancreas of newborn rats (48-64) hr. were used for the in vitro investigation of cyclic AMP, glucose and amino acid interaction in hormonal secretion. The slight discrepancy found in glucagon relaease with radioimmunoassay and binding assay to specific receptors in liver does not affect the ratio of stimulated to control values. The insulin release due to gheophylline dibutyrl cyclic AMP (dbcAMP) or to arginine is glucose-dependent as in adult rats and provides an index for the validity of the preparations. Glucose alone is efficient in stimulating insulin release but does not affect glucagon secretion; however simultaneous addition of 10 mM arginine, alanine, and lysine (A.A.) or of arginine alone resulted in a higher glucagon release at 1.6 mM than at 16.7 mM GLUCOSE. Theophylline (5 mM)and dbcAMP (2mM) induced a 2=fold increase in glucagon release at low or hight glucose concentrations . Incubation of theophylline (10 mM) and A.A. or arginine resulted in a considerable increase in glucagon release. Potentation of the 3 A.A.-induced glucagon reby dbcAMP was about 1800% no matter what the glucose concentration; similar observations were made for insulin with a 700% potentiation of the 3 A.A.effect glucagon was released more effectively by dbcAMP than was insulin,whereas the reverse was observed with theophylline. These findings suggest that knowledge of the cyclic AMP content is essential when assessing the influence of substrates on glucagon release. The combination of substrates with cyclic AMP clearly demonstrated that potentiation of glucagon release occurs mainly with amino acids, whereas for insulin occurs mainly with amino acids, whereas for insulin release it is mainly glucose which potentiates release.", "contents": "Interaction of amino acids and cyclic AMP on the release of insulin and glucagon by newborn rat pancreas. Splenic lobes from the pancreas of newborn rats (48-64) hr. were used for the in vitro investigation of cyclic AMP, glucose and amino acid interaction in hormonal secretion. The slight discrepancy found in glucagon relaease with radioimmunoassay and binding assay to specific receptors in liver does not affect the ratio of stimulated to control values. The insulin release due to gheophylline dibutyrl cyclic AMP (dbcAMP) or to arginine is glucose-dependent as in adult rats and provides an index for the validity of the preparations. Glucose alone is efficient in stimulating insulin release but does not affect glucagon secretion; however simultaneous addition of 10 mM arginine, alanine, and lysine (A.A.) or of arginine alone resulted in a higher glucagon release at 1.6 mM than at 16.7 mM GLUCOSE. Theophylline (5 mM)and dbcAMP (2mM) induced a 2=fold increase in glucagon release at low or hight glucose concentrations . Incubation of theophylline (10 mM) and A.A. or arginine resulted in a considerable increase in glucagon release. Potentation of the 3 A.A.-induced glucagon reby dbcAMP was about 1800% no matter what the glucose concentration; similar observations were made for insulin with a 700% potentiation of the 3 A.A.effect glucagon was released more effectively by dbcAMP than was insulin,whereas the reverse was observed with theophylline. These findings suggest that knowledge of the cyclic AMP content is essential when assessing the influence of substrates on glucagon release. The combination of substrates with cyclic AMP clearly demonstrated that potentiation of glucagon release occurs mainly with amino acids, whereas for insulin occurs mainly with amino acids, whereas for insulin release it is mainly glucose which potentiates release."} {"id": "PMID:162878", "title": "Estrogen receptors in the chick oviduct.", "content": "An estradiol binding component has been identified in the cytoplasmic fraction of the immature chick oviduct. The method used to resolve this receptor differed from the standard sucrose gradient centrifugation approach in that tritiated hormone was present throughout the sucrose gradient. This modification was necessary to preserve the hormone complex during centrifugation. Under these conditions, an similar to 8 S binding component was demonstrated which underwent dissociation to a similar to 5 S component in high ionic strength medium. Binding specificity determinations revealed that this receptor preferentially bound estrogens. Quantitative binding analysis showed that a limited class of binding sites was present with a dissociation constant (K-d) for estradiol of similar to 8.6 times 10-10M. These properties indicate that this binding component may function as a biologic receptor for estrogens in the oviduct.", "contents": "Estrogen receptors in the chick oviduct. An estradiol binding component has been identified in the cytoplasmic fraction of the immature chick oviduct. The method used to resolve this receptor differed from the standard sucrose gradient centrifugation approach in that tritiated hormone was present throughout the sucrose gradient. This modification was necessary to preserve the hormone complex during centrifugation. Under these conditions, an similar to 8 S binding component was demonstrated which underwent dissociation to a similar to 5 S component in high ionic strength medium. Binding specificity determinations revealed that this receptor preferentially bound estrogens. Quantitative binding analysis showed that a limited class of binding sites was present with a dissociation constant (K-d) for estradiol of similar to 8.6 times 10-10M. These properties indicate that this binding component may function as a biologic receptor for estrogens in the oviduct."} {"id": "PMID:162879", "title": "Content of nuclear estradiol receptor complex in rat corpora lutea during pregnancy: relationship to estrogen concentrations and cytosol receptor availability.", "content": "The content of estradiol receptor in cytosol and nuclear cell fractions of rat corpora lutea changed during pregnancy. The binding of (3-H)) estradiol to luteal cell cytosol was high early in pregnancy between days 3-11, decreased on days 12and15 and was low throughout of the remainder of pregnancy. In contrast, the binding of (3-H) estradiol to nuclear receptor, as measured by nuclear exchange assay, was low early in pregnancy, increased between days 10-15, remained high through day 18 and decreased on days 20 and 22. The administration in vivo of estradiol-17beta (40 mug) 1 hr prior to sacrifice stimulated an increase in nuclear receptor content early in pregnancy (days 3,6,8,10-12) but not later in pregnancy (15,18,20, and 22,). These results suggested that the estradiol binding component(s) present in rat luteal cell cytosol early in pregnancy represented available estradiol receptor capable of being translocated to the nucleus in the presence of sufficient estradiol. However, once available receptor has been saturated by endogenous hormone at midgestation, exogenous hormones hasno further effect on no nuclear receptor content. Importantly,loss of nuclear receptor content late in pregnancy appears to reflect decreased levels of total cellular receptor indicating that corpora lutea at the end of pregnancy have lost the primary mecchanism for responding to estrogens Thus, various stages of luteal cell differentiation are associated with changes in the intra-cellular distribution and total cellular content of estradiol receptor suggesting that luteal cell function may be regulated selectively and separately by hormone concentrations and hormone receptor availability.", "contents": "Content of nuclear estradiol receptor complex in rat corpora lutea during pregnancy: relationship to estrogen concentrations and cytosol receptor availability. The content of estradiol receptor in cytosol and nuclear cell fractions of rat corpora lutea changed during pregnancy. The binding of (3-H)) estradiol to luteal cell cytosol was high early in pregnancy between days 3-11, decreased on days 12and15 and was low throughout of the remainder of pregnancy. In contrast, the binding of (3-H) estradiol to nuclear receptor, as measured by nuclear exchange assay, was low early in pregnancy, increased between days 10-15, remained high through day 18 and decreased on days 20 and 22. The administration in vivo of estradiol-17beta (40 mug) 1 hr prior to sacrifice stimulated an increase in nuclear receptor content early in pregnancy (days 3,6,8,10-12) but not later in pregnancy (15,18,20, and 22,). These results suggested that the estradiol binding component(s) present in rat luteal cell cytosol early in pregnancy represented available estradiol receptor capable of being translocated to the nucleus in the presence of sufficient estradiol. However, once available receptor has been saturated by endogenous hormone at midgestation, exogenous hormones hasno further effect on no nuclear receptor content. Importantly,loss of nuclear receptor content late in pregnancy appears to reflect decreased levels of total cellular receptor indicating that corpora lutea at the end of pregnancy have lost the primary mecchanism for responding to estrogens Thus, various stages of luteal cell differentiation are associated with changes in the intra-cellular distribution and total cellular content of estradiol receptor suggesting that luteal cell function may be regulated selectively and separately by hormone concentrations and hormone receptor availability."} {"id": "PMID:162880", "title": "The clearance of ACTH from the plasma of adult and fetal sheep.", "content": "The disappearance of 125-I-ACTH from the circulation of 4 pregnant and fetal sheep has been followed after a single injection to the ewe or fetus. The mean metabolic clearance rate for the fetus and the ewe was 55 and 34 ml/min/kg respectively, giving a half-life in each case of about 1 min. The higher fetal than maternal arterial plasma ACTH concentration has been ascribed to a higher rate of secretion rather than a reduced rate of clearance compared with the ewe. There was no evidence of placental transfer of immunologically reactive ACTH.", "contents": "The clearance of ACTH from the plasma of adult and fetal sheep. The disappearance of 125-I-ACTH from the circulation of 4 pregnant and fetal sheep has been followed after a single injection to the ewe or fetus. The mean metabolic clearance rate for the fetus and the ewe was 55 and 34 ml/min/kg respectively, giving a half-life in each case of about 1 min. The higher fetal than maternal arterial plasma ACTH concentration has been ascribed to a higher rate of secretion rather than a reduced rate of clearance compared with the ewe. There was no evidence of placental transfer of immunologically reactive ACTH."} {"id": "PMID:162881", "title": "Selective proteolysis of the receptor for parathyroid hormone in renal cortex.", "content": "Studies were carried out to determine if the receptors for parathyroid hormone, calcitonin, and prostaglandin E1 could be differentiated in renal cortex. Slices of rabbit renal cortex were incubated in buffer containing theophylline for 1 hr and then in fresh buffer with and without hormone for an additional period of 15 to 30 min. Parathyroid hormone caused a marked increase in 3',5'-AMP in both the tissue and the reaction medium. The maximal increase in 3',5'-AMP in response to prostaglandin E1 was similar to that of parathyroid hormone in the tissue but significantly less in the medium. The maximal response to calcitonin was less in both the tissue and the medium. Addition of 200 mug/ml trypsin to the first incubation abolished the subsequent response to parathyroid hormone in both the tissue and the reaction medium but did not affect the basal concentration of 3',5'-AMP or the response to calcitonin or prostaglandin E1. Controls were carried out to show that the lack of response to parathyroid hormone could not be attributed to hydrolysis of the hormone by residual trypsin. Slices were also homogenized after preincubation with and without trypsin and assayed for adenylate cyclase activity. Incubation with trypsin markedly diminished the increase in enzyme activity in response to parathyroid hormone but did not alter the basal activity or the response to calcitonin or sodium fluoride. The response to prostaglandin E1 was significantly increased. Combinations of any two or the three hormones at maximal concentrations caused an additive increase in adenylate cyclase activity. The results indicate that the receptors for parathyroid hormone, calcitonin and prostaglandin E1 in renal cortex are separate and the receptor for parathyroid hormone can be selectively hydrolyzed by proteolytic digestion.", "contents": "Selective proteolysis of the receptor for parathyroid hormone in renal cortex. Studies were carried out to determine if the receptors for parathyroid hormone, calcitonin, and prostaglandin E1 could be differentiated in renal cortex. Slices of rabbit renal cortex were incubated in buffer containing theophylline for 1 hr and then in fresh buffer with and without hormone for an additional period of 15 to 30 min. Parathyroid hormone caused a marked increase in 3',5'-AMP in both the tissue and the reaction medium. The maximal increase in 3',5'-AMP in response to prostaglandin E1 was similar to that of parathyroid hormone in the tissue but significantly less in the medium. The maximal response to calcitonin was less in both the tissue and the medium. Addition of 200 mug/ml trypsin to the first incubation abolished the subsequent response to parathyroid hormone in both the tissue and the reaction medium but did not affect the basal concentration of 3',5'-AMP or the response to calcitonin or prostaglandin E1. Controls were carried out to show that the lack of response to parathyroid hormone could not be attributed to hydrolysis of the hormone by residual trypsin. Slices were also homogenized after preincubation with and without trypsin and assayed for adenylate cyclase activity. Incubation with trypsin markedly diminished the increase in enzyme activity in response to parathyroid hormone but did not alter the basal activity or the response to calcitonin or sodium fluoride. The response to prostaglandin E1 was significantly increased. Combinations of any two or the three hormones at maximal concentrations caused an additive increase in adenylate cyclase activity. The results indicate that the receptors for parathyroid hormone, calcitonin and prostaglandin E1 in renal cortex are separate and the receptor for parathyroid hormone can be selectively hydrolyzed by proteolytic digestion."} {"id": "PMID:162882", "title": "Identification and measurement of urinary estrone, estradiol-17 beta, estriol, pregnanediol and androsterone during the menstrual cycle of the orangutan.", "content": "Urinary estrone, estradiol-17beta, estriol, pregnanediol and androsterone were identified and measured during 3 menstrual cycles in 2 female orangutans. In 2 of the cycles, the animals excreted 1-8 mug/day estrone, 0.5-6 mug/day estradiol-17beta, 1-8 mug/day estriol, 20-206 mug/day pregnanediol and 120-522 mug/day androsterone during the first half of the menstrual cycle. In the second half of the cycle, corresponding values were 3-21 mug/day estrone, 2-10 mug/day estradiol-17beta, 1-9 mug/day estriol, 54-800 mug/day pregnanediol and 90-1158 mug/day androsterone. In 1 cycle, the estrogen values for the second half were considerably higher, possibly due to the animal becoming pregnant just before this study commenced. The values for estrone and estradiol-17beta are similar to those found in the human and chimpanzee menstrual cycle. The values for estriol were lower than in the human but higher than in the chimpanzee. Levels for urinary pregnanediol and androsterone were significantly lower than in the human. Variations during the menstrual cycle for estrone were characterized by a midcycle peak followed by a second peak in the luteal phase. No definite pattern was apparent for estradiol-17beta or estriol. Both urinary pregnanediol and androsterone levels were low during the first half of the cycle, started to rise just after midcycle, and showed a peak during the second half of the menstrual cycle.", "contents": "Identification and measurement of urinary estrone, estradiol-17 beta, estriol, pregnanediol and androsterone during the menstrual cycle of the orangutan. Urinary estrone, estradiol-17beta, estriol, pregnanediol and androsterone were identified and measured during 3 menstrual cycles in 2 female orangutans. In 2 of the cycles, the animals excreted 1-8 mug/day estrone, 0.5-6 mug/day estradiol-17beta, 1-8 mug/day estriol, 20-206 mug/day pregnanediol and 120-522 mug/day androsterone during the first half of the menstrual cycle. In the second half of the cycle, corresponding values were 3-21 mug/day estrone, 2-10 mug/day estradiol-17beta, 1-9 mug/day estriol, 54-800 mug/day pregnanediol and 90-1158 mug/day androsterone. In 1 cycle, the estrogen values for the second half were considerably higher, possibly due to the animal becoming pregnant just before this study commenced. The values for estrone and estradiol-17beta are similar to those found in the human and chimpanzee menstrual cycle. The values for estriol were lower than in the human but higher than in the chimpanzee. Levels for urinary pregnanediol and androsterone were significantly lower than in the human. Variations during the menstrual cycle for estrone were characterized by a midcycle peak followed by a second peak in the luteal phase. No definite pattern was apparent for estradiol-17beta or estriol. Both urinary pregnanediol and androsterone levels were low during the first half of the cycle, started to rise just after midcycle, and showed a peak during the second half of the menstrual cycle."} {"id": "PMID:162894", "title": "A spectrum of modalities for treating schizophrenia.", "content": "The author suggests there is a temporal sequence of therapies for schizophrenia, in a continuum of somatic, large-group, small-group, and individual modalities. The therapies arrange themselves in the same order when considered on the parameters of individualized care, treatment population, location, targets and goals, and techniques. By matching the four kinds of treatments, and their goals and areas of efficacy, with the schizophrenic's spectrum of changing needs, the clinician can determine what treatment is most appropriate for a patient at a particular time.", "contents": "A spectrum of modalities for treating schizophrenia. The author suggests there is a temporal sequence of therapies for schizophrenia, in a continuum of somatic, large-group, small-group, and individual modalities. The therapies arrange themselves in the same order when considered on the parameters of individualized care, treatment population, location, targets and goals, and techniques. By matching the four kinds of treatments, and their goals and areas of efficacy, with the schizophrenic's spectrum of changing needs, the clinician can determine what treatment is most appropriate for a patient at a particular time."} {"id": "PMID:162895", "title": "Community care for chronic mental patients: the need for a reassessment.", "content": "The release of chronic mental patients from the hospital to the community has been prompted more by political and economic considerations than by any planned treatment strategy. Large numbers of former patients have gone to live in privately operated boarding houses and nursing homes, where staff have had little experience with mental illness, and where conditions are not much different from the back wards of state hospitals of past decades. New models for caring for chronic, dependent patients should be developed; they should incorporate the precepts of an open social system and should be built around the needs of such patients as they themselves perceive them. To date, few state mental hospitals, have had the funding, staff, or support to adequately explore the possibilities of an optimal environment.", "contents": "Community care for chronic mental patients: the need for a reassessment. The release of chronic mental patients from the hospital to the community has been prompted more by political and economic considerations than by any planned treatment strategy. Large numbers of former patients have gone to live in privately operated boarding houses and nursing homes, where staff have had little experience with mental illness, and where conditions are not much different from the back wards of state hospitals of past decades. New models for caring for chronic, dependent patients should be developed; they should incorporate the precepts of an open social system and should be built around the needs of such patients as they themselves perceive them. To date, few state mental hospitals, have had the funding, staff, or support to adequately explore the possibilities of an optimal environment."} {"id": "PMID:162898", "title": "Adenosine 3',5'-monophosphate increases the outflow of aqueous humor from the rabbit eye.", "content": "Direct administration of cyclic-AMP into the anterior chamber increases the outflow facility of the eye for aqueous humor. This is consistent with the hypothesis that catecholamines lower the intraocular pressure of the rabbit eye, at least in part, by a cyclic-AMP-mediated mechanism. This mechanism is active in the outflow channels and increases the rate at which aqueous humor leaves the anterior chamber.", "contents": "Adenosine 3',5'-monophosphate increases the outflow of aqueous humor from the rabbit eye. Direct administration of cyclic-AMP into the anterior chamber increases the outflow facility of the eye for aqueous humor. This is consistent with the hypothesis that catecholamines lower the intraocular pressure of the rabbit eye, at least in part, by a cyclic-AMP-mediated mechanism. This mechanism is active in the outflow channels and increases the rate at which aqueous humor leaves the anterior chamber."} {"id": "PMID:162899", "title": "Keratomycosis in Wisconsin.", "content": "Candida albicans was the most common fungus responsible for mycotic keratitis in our series from a northern climate, as opposed to southern climates where other fungi were more common. Pimaricin was effective in our patients with Candida infections and in one patient with Aspergillus infection that had been unresponsive to previous amphotericin B.", "contents": "Keratomycosis in Wisconsin. Candida albicans was the most common fungus responsible for mycotic keratitis in our series from a northern climate, as opposed to southern climates where other fungi were more common. Pimaricin was effective in our patients with Candida infections and in one patient with Aspergillus infection that had been unresponsive to previous amphotericin B."} {"id": "PMID:162900", "title": "Combined therapeutic approach to malignant lacrimal gland tumors.", "content": "The medical records of 13 patients with primary malignant lesions of the lacrimal gland revealed adenoid cystic carcinoma as the most common malignant tumor. The histologic cell type, neural invasion, and bony destruction were correlated with localized control and ultimate survival. Surgical removal of the lacrimal gland was adequate treatment for low-grade mucoepidermoid carcinoma confined to the gland itself. Combining a radical surgical removal of the area in planned sequence with high voltage radiation therapy offered the only reasonable hope for localized control in the more aggressive cell types or in tumors with neural invasion or bony involvement. A 40%-localized control and survival rate was achieved in the adenoid cystic carcinoma group of patients. Radiation therapy administered for cancer that obviously recurs after surgical resection was generally unsuccessful.", "contents": "Combined therapeutic approach to malignant lacrimal gland tumors. The medical records of 13 patients with primary malignant lesions of the lacrimal gland revealed adenoid cystic carcinoma as the most common malignant tumor. The histologic cell type, neural invasion, and bony destruction were correlated with localized control and ultimate survival. Surgical removal of the lacrimal gland was adequate treatment for low-grade mucoepidermoid carcinoma confined to the gland itself. Combining a radical surgical removal of the area in planned sequence with high voltage radiation therapy offered the only reasonable hope for localized control in the more aggressive cell types or in tumors with neural invasion or bony involvement. A 40%-localized control and survival rate was achieved in the adenoid cystic carcinoma group of patients. Radiation therapy administered for cancer that obviously recurs after surgical resection was generally unsuccessful."} {"id": "PMID:162901", "title": "Hypogammaglobulinemia predisposing to infection in foals.", "content": "Measurement of serum immunoglobulins in 46 foals less than 2 weeks old revealed 9 foals with hypogammaglobulinemia. The hypogammaglobulinemia was attributed to failure in transfer of immunoglobulins from dam to foal via colostrum. Three of the affected foals did not nurse at all, or only slightly, and 2 of these died of infections within a few days after birth, whereas the 3rd foal did not grow as well as normal foals. Six of the affected foals nursed in an apparently normal manner, and 5 of these had nonfatal respiratory infections between 2 and 5 weeks of age. Analysis of serum samples from surviving foals demonstrated that immunoglobulins were eventually produced. One other foal examined had hypogammaglobulinemia at 57 days of age, an age when the foal should have produced large amounts of immunoglobulin independent of passive transfer. This foal had simultaneous infections and hypogammaglobulinemia, but eventually produced normal amounts of immunoglobulin. Cellmediated immunity was normal at 3 months of age. This condition was designated transient hypogammaglobulinemia and was thought to be due to a temporary inability to make immunoglobulins.", "contents": "Hypogammaglobulinemia predisposing to infection in foals. Measurement of serum immunoglobulins in 46 foals less than 2 weeks old revealed 9 foals with hypogammaglobulinemia. The hypogammaglobulinemia was attributed to failure in transfer of immunoglobulins from dam to foal via colostrum. Three of the affected foals did not nurse at all, or only slightly, and 2 of these died of infections within a few days after birth, whereas the 3rd foal did not grow as well as normal foals. Six of the affected foals nursed in an apparently normal manner, and 5 of these had nonfatal respiratory infections between 2 and 5 weeks of age. Analysis of serum samples from surviving foals demonstrated that immunoglobulins were eventually produced. One other foal examined had hypogammaglobulinemia at 57 days of age, an age when the foal should have produced large amounts of immunoglobulin independent of passive transfer. This foal had simultaneous infections and hypogammaglobulinemia, but eventually produced normal amounts of immunoglobulin. Cellmediated immunity was normal at 3 months of age. This condition was designated transient hypogammaglobulinemia and was thought to be due to a temporary inability to make immunoglobulins."} {"id": "PMID:162902", "title": "Viral respiratory infections of horses: structure and function of lungs in relation to viral infection.", "content": "Since the advent of cell culture techniques, numerous viruses have been shown to be related to respiratory diseases in horses. Although the viruses differ in many ways, they cause disease with some common characteristics. This report is a summary of some of the available material from written sources and from personal observations. It is intended to help explain some of the changes observed in viral-induced respiratory disease.", "contents": "Viral respiratory infections of horses: structure and function of lungs in relation to viral infection. Since the advent of cell culture techniques, numerous viruses have been shown to be related to respiratory diseases in horses. Although the viruses differ in many ways, they cause disease with some common characteristics. This report is a summary of some of the available material from written sources and from personal observations. It is intended to help explain some of the changes observed in viral-induced respiratory disease."} {"id": "PMID:162906", "title": "Cell properties after repeated transplantation of spontaneously and of SV40 virus transformed mouse cell lines. I. Growth in culture.", "content": "\"Spontaneously\" or SV40 virus transformed AL/N mouse cell lines were passed repeatedly through syngeneic mice. Cell lines were re-established in culture from minced pieces of tumors in the presence of concentrated fetal calf serum or from tumor cells dispersed by trypsin. The aim of this study was to compare the two cell lines in regard to the selection processes which operate during such procedures by characterization of the resulting cell lines. Measurements of growth in tissue culture on substratum showed no significant difference between any of the transformed cell lines. The SV40 transformed cells and its derivative cells had a low anchorage requirement for growth. The greatest anchorage requirement for growth was in the normal untransformed cells and in the derivative cells from the \"spontaneously\" transformed cells which were established from minced tumors. The spontaneously transformed cells and all derivative cells had high tumorigenicity (TD50 is less than 10-2). The SV40 transformed cells had no observable tumorigenicity (TD50 is greater than 10-8), except when injected into irradiated mice (TD50 = 1-5 X 10-5 in the immunocompetent mice, 5 X 10-4 in the irradiated mice). The SV40 transformed derivative cells maintained their SV40 specific T antigen and their susceptibility to lysis by specific antiserum.", "contents": "Cell properties after repeated transplantation of spontaneously and of SV40 virus transformed mouse cell lines. I. Growth in culture. \"Spontaneously\" or SV40 virus transformed AL/N mouse cell lines were passed repeatedly through syngeneic mice. Cell lines were re-established in culture from minced pieces of tumors in the presence of concentrated fetal calf serum or from tumor cells dispersed by trypsin. The aim of this study was to compare the two cell lines in regard to the selection processes which operate during such procedures by characterization of the resulting cell lines. Measurements of growth in tissue culture on substratum showed no significant difference between any of the transformed cell lines. The SV40 transformed cells and its derivative cells had a low anchorage requirement for growth. The greatest anchorage requirement for growth was in the normal untransformed cells and in the derivative cells from the \"spontaneously\" transformed cells which were established from minced tumors. The spontaneously transformed cells and all derivative cells had high tumorigenicity (TD50 is less than 10-2). The SV40 transformed cells had no observable tumorigenicity (TD50 is greater than 10-8), except when injected into irradiated mice (TD50 = 1-5 X 10-5 in the immunocompetent mice, 5 X 10-4 in the irradiated mice). The SV40 transformed derivative cells maintained their SV40 specific T antigen and their susceptibility to lysis by specific antiserum."} {"id": "PMID:162907", "title": "Growth control in primary fetal rat liver cells in culture.", "content": "Primary fetal rat liver cells cultured in medium deficient in, but not free of, arginine in the presence of dialyzed fetal calf serum grow until the final cell density is attained and cells become quiescent in the Go phase of the cell cycle. When growing cells are transferred into arginine free medium, cells become reversibly arrested in Go. Fetal rat liver cells can be induced to synthesize DNA by addition of high levels of arginine to serum free medium. Low arginine levels in the culture medium do not induce cell growth unless serum is present. Serum stimulates arginine uptake in fetal rat liver cells suggesting that serum growth factor(s) act by increasing intracellular arginine levels high enough to initiate the growth cycle. Fractionation of fetal calf serum by gel filtration on G-200 Sephadex yields a partially purified arginine uptake stimulating activity which is eluted from the column in the same fractions that contain fetal rat liver cell growth promoting activity. Insulin induces DNA synthesis in quiescent fetal rat liver cells. Glucagon reverses the stimulatory effects of insulin. N-6,O-2-Dibutyryl adenosine 3:5-cyclic monophosphoric acid (But2c-AMP) (10-minus4 M) and theophilline (10-minus3 M) inhibit arginine uptake and the initiation of DNA synthesis by serum. The role of arginine in the control of DNA synthesis in fetal rat liver cells and the mechanism of action of serum growth factors are discussed.", "contents": "Growth control in primary fetal rat liver cells in culture. Primary fetal rat liver cells cultured in medium deficient in, but not free of, arginine in the presence of dialyzed fetal calf serum grow until the final cell density is attained and cells become quiescent in the Go phase of the cell cycle. When growing cells are transferred into arginine free medium, cells become reversibly arrested in Go. Fetal rat liver cells can be induced to synthesize DNA by addition of high levels of arginine to serum free medium. Low arginine levels in the culture medium do not induce cell growth unless serum is present. Serum stimulates arginine uptake in fetal rat liver cells suggesting that serum growth factor(s) act by increasing intracellular arginine levels high enough to initiate the growth cycle. Fractionation of fetal calf serum by gel filtration on G-200 Sephadex yields a partially purified arginine uptake stimulating activity which is eluted from the column in the same fractions that contain fetal rat liver cell growth promoting activity. Insulin induces DNA synthesis in quiescent fetal rat liver cells. Glucagon reverses the stimulatory effects of insulin. N-6,O-2-Dibutyryl adenosine 3:5-cyclic monophosphoric acid (But2c-AMP) (10-minus4 M) and theophilline (10-minus3 M) inhibit arginine uptake and the initiation of DNA synthesis by serum. The role of arginine in the control of DNA synthesis in fetal rat liver cells and the mechanism of action of serum growth factors are discussed."} {"id": "PMID:162908", "title": "Phosphorylation but not transport of sugars is enhanced in virus-transformed mouse 3T3 cells.", "content": "The transport and phosphorylation of 2-deoxy-D-glucose are separate and sequential events in both normal and virus-transformed 3T3 cells. The apparent enhancement of 2-dOG uptake by 3T3 cells accompanying virus transformation is not due to an effect on the transport process but to enhanced phosphorylation by intracellular kinases. Phosphorylation of 3-O-methyl-D-glucose does not occur in these cells. Both the rate and extent of transport of this glucose analog is the same in normal cells, SV40 virus-transformed cells and sarcoma virus-transformed cells. The appropriateness of using 3-O-MeG for studies of the glucose transport system of animal cells is examined and discussed.", "contents": "Phosphorylation but not transport of sugars is enhanced in virus-transformed mouse 3T3 cells. The transport and phosphorylation of 2-deoxy-D-glucose are separate and sequential events in both normal and virus-transformed 3T3 cells. The apparent enhancement of 2-dOG uptake by 3T3 cells accompanying virus transformation is not due to an effect on the transport process but to enhanced phosphorylation by intracellular kinases. Phosphorylation of 3-O-methyl-D-glucose does not occur in these cells. Both the rate and extent of transport of this glucose analog is the same in normal cells, SV40 virus-transformed cells and sarcoma virus-transformed cells. The appropriateness of using 3-O-MeG for studies of the glucose transport system of animal cells is examined and discussed."} {"id": "PMID:162909", "title": "Isolation and characterization of revertant cell lines. VII. DNA synthesis and mitotic rate of serum-sensitive revertants in non-permissive growth conditions.", "content": "The ability to synthesize DNA and enter mitosis was studied in Balb/c and Swiss 3T3 cells, SV40 and MSV-transformed 3T3 cells and revertants of these transformed cells in cultures of different serum concentrations and cell densities. Three ways were found by which cells were able to maintain a constant cell number in non-permissive growth conditions: cessation of DNA synthesis, synthesis of DNA coupled with failure to enter mitosis, and the slow traverse of the cell cycle coupled with cell shedding. Growth control of the revertant of an MSV-transformed Balb/3T3 cell most closely resembled that of Balb or Swiss 3T3. This line did not grow in 1% serum and did not synthesize DNA in either non-permissive condition. Serum-sensitive revertants of SV40-transformed 3T3 cells are also unable to grow in 1% serum and also do not grow beyond confluence in 10% serum, but these cells differ from 3T3 in the manner in which this growth arrest is accomplished. In 1% serum, revertants synthesize DNA but do not enter mitosis. At confluence in 10% serum, they slowly traverse the cell cycle, with dividing cells replacing cells that are shed into the medium.", "contents": "Isolation and characterization of revertant cell lines. VII. DNA synthesis and mitotic rate of serum-sensitive revertants in non-permissive growth conditions. The ability to synthesize DNA and enter mitosis was studied in Balb/c and Swiss 3T3 cells, SV40 and MSV-transformed 3T3 cells and revertants of these transformed cells in cultures of different serum concentrations and cell densities. Three ways were found by which cells were able to maintain a constant cell number in non-permissive growth conditions: cessation of DNA synthesis, synthesis of DNA coupled with failure to enter mitosis, and the slow traverse of the cell cycle coupled with cell shedding. Growth control of the revertant of an MSV-transformed Balb/3T3 cell most closely resembled that of Balb or Swiss 3T3. This line did not grow in 1% serum and did not synthesize DNA in either non-permissive condition. Serum-sensitive revertants of SV40-transformed 3T3 cells are also unable to grow in 1% serum and also do not grow beyond confluence in 10% serum, but these cells differ from 3T3 in the manner in which this growth arrest is accomplished. In 1% serum, revertants synthesize DNA but do not enter mitosis. At confluence in 10% serum, they slowly traverse the cell cycle, with dividing cells replacing cells that are shed into the medium."} {"id": "PMID:162910", "title": "The origin of chicken hematopoietic colonies as assayed in semisolid agar.", "content": "This investigation was undertaken to determine whether primitive stem cells and/or fully differentiated macrophages were the source of in vitro colonies derived from hematopoietic tissues. The chicken colony-forming cell (CFC) present in uncultured yolk sac was a nonadherent, presumably undifferentiated cell. The efficiency of colony formation in this case was approximately 0.08%. In contrast to uncultured yolk sac, the CFC present in one-week old yolk sac cultures was evidently a macrophage. Yolk sac cultures, which consisted of greater than 99% macrophages, produced colonies with an efficiency of 1-5% while cultures derived from peritoneal macrophages produced colonies with an efficiency of 10%. Silica selectively destroyed macrophages and reduced the colony forming efficiency of cells derived from yolk sac cultures.", "contents": "The origin of chicken hematopoietic colonies as assayed in semisolid agar. This investigation was undertaken to determine whether primitive stem cells and/or fully differentiated macrophages were the source of in vitro colonies derived from hematopoietic tissues. The chicken colony-forming cell (CFC) present in uncultured yolk sac was a nonadherent, presumably undifferentiated cell. The efficiency of colony formation in this case was approximately 0.08%. In contrast to uncultured yolk sac, the CFC present in one-week old yolk sac cultures was evidently a macrophage. Yolk sac cultures, which consisted of greater than 99% macrophages, produced colonies with an efficiency of 1-5% while cultures derived from peritoneal macrophages produced colonies with an efficiency of 10%. Silica selectively destroyed macrophages and reduced the colony forming efficiency of cells derived from yolk sac cultures."} {"id": "PMID:162911", "title": "Mutants of chinese hamster cells resistant to adenosine.", "content": "Chinese hamster cells do not grow in medium containing high concentrations of adenosine because pyrimidine biosynthesis is inhibited. Adenosine metabolism was examined in two mutant cell lines isolated on the basis of resistance to adenosine. One line was deficient in adenosine kinase suggesting that high intracellular AMP concentrations may block pyrimidine synthesis indirectly in wild type cells by inhibiting PRPP synthetase. Although no enzymatic defect could be identified in the other cell line, these cells inefficiently utilize adenosine supplied in the medium.", "contents": "Mutants of chinese hamster cells resistant to adenosine. Chinese hamster cells do not grow in medium containing high concentrations of adenosine because pyrimidine biosynthesis is inhibited. Adenosine metabolism was examined in two mutant cell lines isolated on the basis of resistance to adenosine. One line was deficient in adenosine kinase suggesting that high intracellular AMP concentrations may block pyrimidine synthesis indirectly in wild type cells by inhibiting PRPP synthetase. Although no enzymatic defect could be identified in the other cell line, these cells inefficiently utilize adenosine supplied in the medium."} {"id": "PMID:162912", "title": "Allergens of mammalian origin. II. Characterization of allergens extracted from rat, mouse, guinea pig, and rabbit pelts.", "content": "Aqueous extracts prepared from lyophilized, defatted rat, mouse, guinea pig, and rabbit pelts elicited intense wheal-and-flare responses in the skin of a high proportion of patients who were clinically sensitive to these animals. The major allergens in each extract were nondialyzable. Skin test reactions to rat, mouse, and guinea pig serum were common in patients allergic to these animals. The fractions of rat, mouse, and rabbit pelt extract showing maximum allergenic activity contained proteins with the electrophoretic mobility of serum albumin. Fractions of guinea pig pelt extract with maximum allergenic activity were of prealbumin mobility and contained little stainable protein. On Sephadex G-100 gel filtration, most allergen from rat, mouse, and guinea pig pelt extracts was recovered in fractions containing proteins with a molecular weight range of 10,000 to 25,000 daltons. Allergen in rabbit pelt extract had a slightly higher molecular weight range of 18,000 to 38,000 daltons.", "contents": "Allergens of mammalian origin. II. Characterization of allergens extracted from rat, mouse, guinea pig, and rabbit pelts. Aqueous extracts prepared from lyophilized, defatted rat, mouse, guinea pig, and rabbit pelts elicited intense wheal-and-flare responses in the skin of a high proportion of patients who were clinically sensitive to these animals. The major allergens in each extract were nondialyzable. Skin test reactions to rat, mouse, and guinea pig serum were common in patients allergic to these animals. The fractions of rat, mouse, and rabbit pelt extract showing maximum allergenic activity contained proteins with the electrophoretic mobility of serum albumin. Fractions of guinea pig pelt extract with maximum allergenic activity were of prealbumin mobility and contained little stainable protein. On Sephadex G-100 gel filtration, most allergen from rat, mouse, and guinea pig pelt extracts was recovered in fractions containing proteins with a molecular weight range of 10,000 to 25,000 daltons. Allergen in rabbit pelt extract had a slightly higher molecular weight range of 18,000 to 38,000 daltons."} {"id": "PMID:162919", "title": "Epidermal chalone and cyclic AMP: an in vivo study.", "content": "Water extracts of skin contain two factors that inhibit epidermal cell proliferation: one substance inhibits epidermal cells in the G2 phase (the epidermal G2 inhibitor), and another inhibits the transit of cells from the G1 phase into the S phase (the epidermal G1 inhibitor). Pretreatment of mice with a beta-receptor antagonist (propranolol) abolished the activity of the G2 inhibitor but not that of the G1 inhibitor. After pretreatment with both propranolol and a phosphodiesterase inhibitor (caffine)the G2 inhibitor had full effect. Cafine alone had a moderately inhibitory effect on epidermal G2 cells and enhanced the depressing effect of the G1 inhibitor on epidermal DNA synthesis. AMP level in epidermis to be active. Cyclic AMP is probably also involved in the regulation of the rate of transit of epidermal G1 cells into the S phase but the epidermal cyclic AMP level seems not to be so critical for the efficacy of the epidermal G2 inhibitor in epidermal cell differentiation.", "contents": "Epidermal chalone and cyclic AMP: an in vivo study. Water extracts of skin contain two factors that inhibit epidermal cell proliferation: one substance inhibits epidermal cells in the G2 phase (the epidermal G2 inhibitor), and another inhibits the transit of cells from the G1 phase into the S phase (the epidermal G1 inhibitor). Pretreatment of mice with a beta-receptor antagonist (propranolol) abolished the activity of the G2 inhibitor but not that of the G1 inhibitor. After pretreatment with both propranolol and a phosphodiesterase inhibitor (caffine)the G2 inhibitor had full effect. Cafine alone had a moderately inhibitory effect on epidermal G2 cells and enhanced the depressing effect of the G1 inhibitor on epidermal DNA synthesis. AMP level in epidermis to be active. Cyclic AMP is probably also involved in the regulation of the rate of transit of epidermal G1 cells into the S phase but the epidermal cyclic AMP level seems not to be so critical for the efficacy of the epidermal G2 inhibitor in epidermal cell differentiation."} {"id": "PMID:162920", "title": "In vitro epidermal cell proliferation in rat skin plugs.", "content": "Full-thickness skin plugs from immature and adult rats have been shown to incorporate -3H-thymidine in vitro in a semisynchronous fashion for up to 54 hr. DNA synthesis is minimal at 16 hr post sacrifice but increases again at 24 and 48 hr, and cells in S phase at 48 hr have passed through at least one mitosis in vitro (between 32 and 39 hr). Advantage can be taken of this semisynchronous burst of DNA synthetic activity to test the effects of potential inhibitors of skin cell proliferation, and to determine at which phase of the cell cyclic these inhibitors act. High concentrations of epinephrine or isoproterenol (10--5 M) are required to cause inhibition but the effect is specific for the G2 phase of the cell cycle. Propranolol does not demonstrate beta-antagonism in this system, since it is a very potent inhibitor acting in G1 phase. Dibutyryl cycle AMP and theophylline have two effects: one is a specific inhibitory action on cells in the G2 phase and the second is a short-term action limiting thymidine uptake by cells in S phase without affecting the transition of cells from G1 to S.", "contents": "In vitro epidermal cell proliferation in rat skin plugs. Full-thickness skin plugs from immature and adult rats have been shown to incorporate -3H-thymidine in vitro in a semisynchronous fashion for up to 54 hr. DNA synthesis is minimal at 16 hr post sacrifice but increases again at 24 and 48 hr, and cells in S phase at 48 hr have passed through at least one mitosis in vitro (between 32 and 39 hr). Advantage can be taken of this semisynchronous burst of DNA synthetic activity to test the effects of potential inhibitors of skin cell proliferation, and to determine at which phase of the cell cyclic these inhibitors act. High concentrations of epinephrine or isoproterenol (10--5 M) are required to cause inhibition but the effect is specific for the G2 phase of the cell cycle. Propranolol does not demonstrate beta-antagonism in this system, since it is a very potent inhibitor acting in G1 phase. Dibutyryl cycle AMP and theophylline have two effects: one is a specific inhibitory action on cells in the G2 phase and the second is a short-term action limiting thymidine uptake by cells in S phase without affecting the transition of cells from G1 to S."} {"id": "PMID:162921", "title": "Clinically useful method for the isolation of respiratory syncytial virus.", "content": "A simple method for the isolation of respiratory syncytial virus (RSV) is reported; it is relatively rapid and results in a high frequency of recovery of virus. A nasal secretion specimen with high titers of virus is inoculated at the bedside onto susceptible cell lines to avoid loss of viral infectivity due to liability of the virus. During an outbreak of RSV, viral specimens were obtained by this method from all young children admitted to the hospital with lower respiratory tract disease. RSV or influenza A virus was recovered from 89% of these 45 children. RSV was isolated from 87% of those with pneumonia. RSV was recovered 60% less often from specimens obtained simultaneously by conventional nasopharyngeal swabs. Identification of RSV cytopathic effect was more rapid with use of the bedside nasal wash method and was accomplished in an average of four days. Hence, this information was available to the clinicician when it was still useful in the management of the patient's illness.", "contents": "Clinically useful method for the isolation of respiratory syncytial virus. A simple method for the isolation of respiratory syncytial virus (RSV) is reported; it is relatively rapid and results in a high frequency of recovery of virus. A nasal secretion specimen with high titers of virus is inoculated at the bedside onto susceptible cell lines to avoid loss of viral infectivity due to liability of the virus. During an outbreak of RSV, viral specimens were obtained by this method from all young children admitted to the hospital with lower respiratory tract disease. RSV or influenza A virus was recovered from 89% of these 45 children. RSV was isolated from 87% of those with pneumonia. RSV was recovered 60% less often from specimens obtained simultaneously by conventional nasopharyngeal swabs. Identification of RSV cytopathic effect was more rapid with use of the bedside nasal wash method and was accomplished in an average of four days. Hence, this information was available to the clinicician when it was still useful in the management of the patient's illness."} {"id": "PMID:162922", "title": "Evaluation of four antiviral agents in the treatment of herpes simplex encephalitis in a rat model.", "content": "Three hundred four animals were used for the systematic evaluation of the in vivo efficacy of 5-iodo-2'-deoxyuridine (IUDR), cytosire arabinoside, 9-beta-arabinofuranosyladenine, and isoprinosine in the therapy of herpes simplex encephalitis in an adult rat model. Type 1 herpes simplex virus was inoculated intracerabrally, and drug was administered by the intraperitoneal route. All experiments included tests for toxicity and viral controls, Eight sets of experiments were used for evaluation of ttherapy with IUDR; the inoculum ranged from 64 to 2,000 TCID50, dose of drug from 0.1 mg/g to 1.0 mg/g per day, and duration of therapy from one to five days. There was no significant improvement in the number of animals surviving or in the survival time when the viral controls were compared with mice in treated groups. A slight trend toward increased survival time and decreased titer of virus in the brains of animals treated with IUDR was noted in the group that received the largest dose. Three or four sets of experiments were used to evaluate each of the other three antiviral drugs. Results were similar to those reported for IUDR. These results indicate a need for further studies, including investigations of the pharmacology and toxicity of these antiviral agents, to establish more clearly the dosages of drug that are therapeutic, those that are toxic, and ratios of these dosages.", "contents": "Evaluation of four antiviral agents in the treatment of herpes simplex encephalitis in a rat model. Three hundred four animals were used for the systematic evaluation of the in vivo efficacy of 5-iodo-2'-deoxyuridine (IUDR), cytosire arabinoside, 9-beta-arabinofuranosyladenine, and isoprinosine in the therapy of herpes simplex encephalitis in an adult rat model. Type 1 herpes simplex virus was inoculated intracerabrally, and drug was administered by the intraperitoneal route. All experiments included tests for toxicity and viral controls, Eight sets of experiments were used for evaluation of ttherapy with IUDR; the inoculum ranged from 64 to 2,000 TCID50, dose of drug from 0.1 mg/g to 1.0 mg/g per day, and duration of therapy from one to five days. There was no significant improvement in the number of animals surviving or in the survival time when the viral controls were compared with mice in treated groups. A slight trend toward increased survival time and decreased titer of virus in the brains of animals treated with IUDR was noted in the group that received the largest dose. Three or four sets of experiments were used to evaluate each of the other three antiviral drugs. Results were similar to those reported for IUDR. These results indicate a need for further studies, including investigations of the pharmacology and toxicity of these antiviral agents, to establish more clearly the dosages of drug that are therapeutic, those that are toxic, and ratios of these dosages."} {"id": "PMID:162923", "title": "Treatment of variola major with adenine arabinoside.", "content": "A double-blind study of the efficacy of adenine arabinoside in the treatment of patients with variola major was conducted. Adenine arabinoside (20 mg/kg of body weight) was given to patients intravenously every 24 hr for seven days in a 8-hr infusion. Five of the nine patients receiving adinine arabinoside died, and four of 11 patients receiving placebo died. Mortality was related to the severity of illness for both groups of patients. No difference was found between the drug and control groups in number of febrile days after initiation of therapy or in the period during which it was possible to isolate virus from skin lisions, throat swabs, and sources of clotted blood. Formation of scabs on skin lesions was complete 8.3 days after the initiation of therapy for the drug group and after 11.3 days for the control group. The findings suggest that adenine arabinoside is not effective in the chemotherapy of smallpox.", "contents": "Treatment of variola major with adenine arabinoside. A double-blind study of the efficacy of adenine arabinoside in the treatment of patients with variola major was conducted. Adenine arabinoside (20 mg/kg of body weight) was given to patients intravenously every 24 hr for seven days in a 8-hr infusion. Five of the nine patients receiving adinine arabinoside died, and four of 11 patients receiving placebo died. Mortality was related to the severity of illness for both groups of patients. No difference was found between the drug and control groups in number of febrile days after initiation of therapy or in the period during which it was possible to isolate virus from skin lisions, throat swabs, and sources of clotted blood. Formation of scabs on skin lesions was complete 8.3 days after the initiation of therapy for the drug group and after 11.3 days for the control group. The findings suggest that adenine arabinoside is not effective in the chemotherapy of smallpox."} {"id": "PMID:162924", "title": "Treatment of variola major with cytosine arabinoside.", "content": "A controlled study of the efficacy of cytosine arabinoside in the treatment of patients with variola major was performed. Cytosine aravinoside was given intravenously at a dose approximating 3 mg/kg of body weight every 24 hr for up to seven days. All nine patients receiving cytosine arabinoside and four of the 11 patients receiving placebo died. In three of the patients receiving cytosine aravinoside, death occurred late in the illness at a time when the patient's lesions began to dry up, the patient's temperature became normal, and the patient's general condition appeared to improve. The virus could be isolated from the blood at day 7 from three of four patients treated with cytosine arabinoside as compared with zero of six control patients. Hematologic data showed a depression in the number of circulating granulocytes. It is possible that the drug lowered the resistance to infection either through direct suppression of granulocytes or through interference with other immune mechanisms. Cytosine arabinside administered in the doses used in this study is not effective in the treatment of variola major.", "contents": "Treatment of variola major with cytosine arabinoside. A controlled study of the efficacy of cytosine arabinoside in the treatment of patients with variola major was performed. Cytosine aravinoside was given intravenously at a dose approximating 3 mg/kg of body weight every 24 hr for up to seven days. All nine patients receiving cytosine arabinoside and four of the 11 patients receiving placebo died. In three of the patients receiving cytosine aravinoside, death occurred late in the illness at a time when the patient's lesions began to dry up, the patient's temperature became normal, and the patient's general condition appeared to improve. The virus could be isolated from the blood at day 7 from three of four patients treated with cytosine arabinoside as compared with zero of six control patients. Hematologic data showed a depression in the number of circulating granulocytes. It is possible that the drug lowered the resistance to infection either through direct suppression of granulocytes or through interference with other immune mechanisms. Cytosine arabinside administered in the doses used in this study is not effective in the treatment of variola major."} {"id": "PMID:162925", "title": "Invasion of the central nervous system by herpes simplex virus type 1 after subcutaneous inoculation of immunosuppressed mice.", "content": "Young adult mice given subcutaneous inoculations in the rear footpad with herpes simplex virus type 1 were found to be resistant to infection unless they were immunosuppressed with sublethal doses of irradiation or cyclophosphamide. In these mice, virus multiplied in the sciatic nerve three to four days after inoculation. This development was followed by multiplication of virus in the spinal cord and brain, which caused death of the mice in about eight days. No virus was detected in the blood or liver. Resection of the sciatic nerve significantly increased the number of immunosuppressed mice surviving footpad inoculation. Passive transfer of antibody had no effect on the course of infection. Sublethal doses of irradiation or cyclophosphamide can apparently increase the susceptibility of the central nervous system to invasion of Herpesvirus from extraneural sites of infection by spread along peripheral nerves.", "contents": "Invasion of the central nervous system by herpes simplex virus type 1 after subcutaneous inoculation of immunosuppressed mice. Young adult mice given subcutaneous inoculations in the rear footpad with herpes simplex virus type 1 were found to be resistant to infection unless they were immunosuppressed with sublethal doses of irradiation or cyclophosphamide. In these mice, virus multiplied in the sciatic nerve three to four days after inoculation. This development was followed by multiplication of virus in the spinal cord and brain, which caused death of the mice in about eight days. No virus was detected in the blood or liver. Resection of the sciatic nerve significantly increased the number of immunosuppressed mice surviving footpad inoculation. Passive transfer of antibody had no effect on the course of infection. Sublethal doses of irradiation or cyclophosphamide can apparently increase the susceptibility of the central nervous system to invasion of Herpesvirus from extraneural sites of infection by spread along peripheral nerves."} {"id": "PMID:162926", "title": "Classification of enterotoxins on the basis of activity in cell culture.", "content": "Two cell culture systems were used in a study of the biological properties of several bacterial enterotoxins in vitro. By means of one model, in which HeLa cell monolayers were used, cytotoxic effects, interms of detachment of cells from a glass surface due to cell death, were assayed. By means of the second model, activation of the adenyl cyclase-cyclic adenosine 3', 5'-monophosphate (AMP) system, in terms of increased steroidogenesis by Y-1 adrenal cells (an effect which we have termed cytotonic), was assayed. None of the four toxins manifested both properties. Rather there was a clear segregation into two cytotoxic enterotoxins (Shigella dysenteriae type 1 and Clostridium perfingens) and two cytotonic products (Vibrio cholerae and Escherichia coli). These data raise the possibility that some enterotoxins may not interact with the adenyl cyclase-cyclic AMP system; this possibility has also been suggested by studies of the toxin of S. dysenteriae type 1 in the rabbit small bowel. These cell culture systems may therefore serve as convenient models for the study of the mechanism of action of both classes of enterotoxin.", "contents": "Classification of enterotoxins on the basis of activity in cell culture. Two cell culture systems were used in a study of the biological properties of several bacterial enterotoxins in vitro. By means of one model, in which HeLa cell monolayers were used, cytotoxic effects, interms of detachment of cells from a glass surface due to cell death, were assayed. By means of the second model, activation of the adenyl cyclase-cyclic adenosine 3', 5'-monophosphate (AMP) system, in terms of increased steroidogenesis by Y-1 adrenal cells (an effect which we have termed cytotonic), was assayed. None of the four toxins manifested both properties. Rather there was a clear segregation into two cytotoxic enterotoxins (Shigella dysenteriae type 1 and Clostridium perfingens) and two cytotonic products (Vibrio cholerae and Escherichia coli). These data raise the possibility that some enterotoxins may not interact with the adenyl cyclase-cyclic AMP system; this possibility has also been suggested by studies of the toxin of S. dysenteriae type 1 in the rabbit small bowel. These cell culture systems may therefore serve as convenient models for the study of the mechanism of action of both classes of enterotoxin."} {"id": "PMID:162927", "title": "In vitro labeling of beta-apolipoprotein with 3H or 14C and preliminary application to turnover studies.", "content": "3-H- or 14-C-labeled methyl groups were introduced into apolipoproteins of human and pig low density lipoproteins (LDL). 98% of the label was recovered in the apoprotein of radiomethylated LDL. Such methylated lipoprotein was compared with the corresponding unlabeled LDL with respect to its electrophoretic and immunochemical properties, and its behavior in the analytical ultracentrifuge. The data demonstrated that neither the human nor pig LDL underwent gross changes as a result of methylation. The applicability of radiomethylated pig LDL as a tracer for studying the turnover of LDL in pigs was examined. The results showed that the behavior of unscreened and screened 3-H-labeled LDL was similar. The LDL disappeared with an initial t1/2 of 1.1 hr and a later t1/2 of 30 hr. These values agreed well with those reported for radioiodinated LDL. The technique of radiomethylation of lipoprotein may afford an advantage over radioiodination as it may label peptides that do not have tyrosine.", "contents": "In vitro labeling of beta-apolipoprotein with 3H or 14C and preliminary application to turnover studies. 3-H- or 14-C-labeled methyl groups were introduced into apolipoproteins of human and pig low density lipoproteins (LDL). 98% of the label was recovered in the apoprotein of radiomethylated LDL. Such methylated lipoprotein was compared with the corresponding unlabeled LDL with respect to its electrophoretic and immunochemical properties, and its behavior in the analytical ultracentrifuge. The data demonstrated that neither the human nor pig LDL underwent gross changes as a result of methylation. The applicability of radiomethylated pig LDL as a tracer for studying the turnover of LDL in pigs was examined. The results showed that the behavior of unscreened and screened 3-H-labeled LDL was similar. The LDL disappeared with an initial t1/2 of 1.1 hr and a later t1/2 of 30 hr. These values agreed well with those reported for radioiodinated LDL. The technique of radiomethylation of lipoprotein may afford an advantage over radioiodination as it may label peptides that do not have tyrosine."} {"id": "PMID:162928", "title": "Splanchnic and hepatic triglyceride secretion during hypercaloric intravenous glucose infusion in conscious swine.", "content": "We have validated a radiochemical technique for measuring the rate of secretion of plasma triglycerides from the liver and/or splanchnic region during the consumption of glucose under isotopic steady-state conditions. Values obtained with this technique correlated closely with those based on transhepatic or transsplanchnic chemical gradients (r = 0.95). Likewise, values for secretion of triglycerides obtained with the radiochemical technique correlated closely with those obtained for extrahepatic or extrasplanchnic triglyceride clearance. Values for mean net splanchnic and hepatic secretion of plasma triglyceride fatty acids, transported essentially in very low density lipoproteins, were 1.9 and 2.0 mumoles/min.kg body wt0.75, respectively, about one-half of the rate of transport of free fatty acids. However, the fraction of triglyceride fatty acids of plasma very low density lipoproteins that was derived from plasma free fatty acids averaged 9% and that derived from glucose, though increasing with time, reached only 2% after constant intravenous infusion of radioglucose for 5 hr. Porcine hepatic secretion of plasma triglycerides is large in the glucose-fed state, and the secreted triglyceride fatty acids evidently are derived from stored fat or glycon.", "contents": "Splanchnic and hepatic triglyceride secretion during hypercaloric intravenous glucose infusion in conscious swine. We have validated a radiochemical technique for measuring the rate of secretion of plasma triglycerides from the liver and/or splanchnic region during the consumption of glucose under isotopic steady-state conditions. Values obtained with this technique correlated closely with those based on transhepatic or transsplanchnic chemical gradients (r = 0.95). Likewise, values for secretion of triglycerides obtained with the radiochemical technique correlated closely with those obtained for extrahepatic or extrasplanchnic triglyceride clearance. Values for mean net splanchnic and hepatic secretion of plasma triglyceride fatty acids, transported essentially in very low density lipoproteins, were 1.9 and 2.0 mumoles/min.kg body wt0.75, respectively, about one-half of the rate of transport of free fatty acids. However, the fraction of triglyceride fatty acids of plasma very low density lipoproteins that was derived from plasma free fatty acids averaged 9% and that derived from glucose, though increasing with time, reached only 2% after constant intravenous infusion of radioglucose for 5 hr. Porcine hepatic secretion of plasma triglycerides is large in the glucose-fed state, and the secreted triglyceride fatty acids evidently are derived from stored fat or glycon."} {"id": "PMID:162929", "title": "Accumulation of oxygenated steryl esters in Wolman's disease.", "content": "7alpha- and 7beta-hydroxycholesteryl esters, 7-ketocholesteryl esters, and 5,6alpha- and 5,6beta-epoxycholesteryl esters have been identified in tissues of patients affected by Wolman's disease. Their structural identities were determined by mass spectroscopy and nuclear magnetic resonance spectroscopy and confirmed by chemical synthesis. It is postulated that cholesteryl ester hydrolase deficiency in Wolman's disease might lead to accumulation of oxygenated steryl esters in vivo and impairment of bile acid formation.", "contents": "Accumulation of oxygenated steryl esters in Wolman's disease. 7alpha- and 7beta-hydroxycholesteryl esters, 7-ketocholesteryl esters, and 5,6alpha- and 5,6beta-epoxycholesteryl esters have been identified in tissues of patients affected by Wolman's disease. Their structural identities were determined by mass spectroscopy and nuclear magnetic resonance spectroscopy and confirmed by chemical synthesis. It is postulated that cholesteryl ester hydrolase deficiency in Wolman's disease might lead to accumulation of oxygenated steryl esters in vivo and impairment of bile acid formation."} {"id": "PMID:162930", "title": "Comparison of exchange of alpha-tocopherol and free cholesterol between rat plasma lipoproteins and erythrocytes.", "content": "The simultaneous exchange of (3h)tocopherol and (14C)cholesterol between rat plasma, rat plasma lipoproteins, and RBC was studied in vitro to compare quantitavely (a) the fractional exchange rates and (b) the half-times for isotope equilibration. In all incubations of RBC with plasma or with plasma lipoprotein fractions, (14C)cholesterol approached equilibrium more rapidly than (3H)tocopherol. When the RBC contained the initial radioactivity, the half-times for equilibration with plasma of cholesterol and of tocopherol were 1.0 and 2.2 hr, respectively. However, the fractional exchange rates (KRBC leads to plasma) were 0.097/hr for cholesterol and 0.188/hr for tocopherol, indicating that the RBC tocopherol pool is turning over almost twice as rapidly as the RBC cholesterol pool. The rat plasma lipoproteins were separated into five fractions by successive ultracentrifugation. Only two fractions, the high density lipoproteins (d 1.063-1.21) and the very low density lipoproteins (d is less than 1.006), participated to a significant extent in the exchange of either tocopherol or cholesterol with RBC. Cholesterol exchange between individual rat plasma lipoproteins and RBC had the same half-times for isotope equilibrium for the very low and high density lipoproteins, and the RBC fractional exchange rates were proportional to the amount of cholesterol in the lipoproteins. In tocopherol exchange between individual rat plasma lipoproteins and RBC, the very low density lipoprotein tocopherol did not equilibrate completely with the RBC. However, the initial rate of tocopherol exchange appeared to be the same for very low and high density lipoproteins. The very low density lipoproteins were disrupted by repeated freezing and thawing or by dehydrating and rehydrating, and analysis of the resulting lipoproteins indicated that free cholesterol was associated more closely than tocopherol with the phospholipid-protein portion of the molecule, which is thought to be on the surface. This difference in distribution of tocopherol and free cholesterol within very low density lipoproteins could account for their different rates of exchange and for the nonequilibrium of tocopherol between RBC and very low density lipoproteins.", "contents": "Comparison of exchange of alpha-tocopherol and free cholesterol between rat plasma lipoproteins and erythrocytes. The simultaneous exchange of (3h)tocopherol and (14C)cholesterol between rat plasma, rat plasma lipoproteins, and RBC was studied in vitro to compare quantitavely (a) the fractional exchange rates and (b) the half-times for isotope equilibration. In all incubations of RBC with plasma or with plasma lipoprotein fractions, (14C)cholesterol approached equilibrium more rapidly than (3H)tocopherol. When the RBC contained the initial radioactivity, the half-times for equilibration with plasma of cholesterol and of tocopherol were 1.0 and 2.2 hr, respectively. However, the fractional exchange rates (KRBC leads to plasma) were 0.097/hr for cholesterol and 0.188/hr for tocopherol, indicating that the RBC tocopherol pool is turning over almost twice as rapidly as the RBC cholesterol pool. The rat plasma lipoproteins were separated into five fractions by successive ultracentrifugation. Only two fractions, the high density lipoproteins (d 1.063-1.21) and the very low density lipoproteins (d is less than 1.006), participated to a significant extent in the exchange of either tocopherol or cholesterol with RBC. Cholesterol exchange between individual rat plasma lipoproteins and RBC had the same half-times for isotope equilibrium for the very low and high density lipoproteins, and the RBC fractional exchange rates were proportional to the amount of cholesterol in the lipoproteins. In tocopherol exchange between individual rat plasma lipoproteins and RBC, the very low density lipoprotein tocopherol did not equilibrate completely with the RBC. However, the initial rate of tocopherol exchange appeared to be the same for very low and high density lipoproteins. The very low density lipoproteins were disrupted by repeated freezing and thawing or by dehydrating and rehydrating, and analysis of the resulting lipoproteins indicated that free cholesterol was associated more closely than tocopherol with the phospholipid-protein portion of the molecule, which is thought to be on the surface. This difference in distribution of tocopherol and free cholesterol within very low density lipoproteins could account for their different rates of exchange and for the nonequilibrium of tocopherol between RBC and very low density lipoproteins."} {"id": "PMID:162931", "title": "3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human hair roots.", "content": "The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (1.1.1.34) was measured in isolated human hair roots. In growing scalp hair roots, the amount of enzyme activity per cell was surprisingly high and was of the same order of magnitude as has been reported for human liver cells and for human fibroblasts cultured in the absence of low density lipoproteins. Hair root enzyme activity showed no diurnal variation, was unaffected by cholestyramine feeding, and was similar in 14 normal subjects, one patient with abetalipoproteinemia, and one homozygote and three heterozygotes with familial hypercholesterolemia. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hair roots appears to be unrelated to the level of low density lipoproteins in the plasma.", "contents": "3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human hair roots. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (1.1.1.34) was measured in isolated human hair roots. In growing scalp hair roots, the amount of enzyme activity per cell was surprisingly high and was of the same order of magnitude as has been reported for human liver cells and for human fibroblasts cultured in the absence of low density lipoproteins. Hair root enzyme activity showed no diurnal variation, was unaffected by cholestyramine feeding, and was similar in 14 normal subjects, one patient with abetalipoproteinemia, and one homozygote and three heterozygotes with familial hypercholesterolemia. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hair roots appears to be unrelated to the level of low density lipoproteins in the plasma."} {"id": "PMID:162932", "title": "In vitro analysis of gene depression in goldfish choroidal melanophores.", "content": "The common goldfish depigments its larval choroidal melanophores as well as the skin melanophores for about two to three months following hatching. Thereafter it begins to show a characteristic xanthic coloration. This depigmentation is under the control of depigmentation genes Dp1 and Dp2. The larval choroidal melanophores of the common goldfish were cultured in vitro for more than four months without showing any sign of depigmentation. During the same period the skin and choroidal melanophores in the ACTH to the culture medium had no effect on depigmentation. The mechanisms of depigmentation in the goldfish are discussed.", "contents": "In vitro analysis of gene depression in goldfish choroidal melanophores. The common goldfish depigments its larval choroidal melanophores as well as the skin melanophores for about two to three months following hatching. Thereafter it begins to show a characteristic xanthic coloration. This depigmentation is under the control of depigmentation genes Dp1 and Dp2. The larval choroidal melanophores of the common goldfish were cultured in vitro for more than four months without showing any sign of depigmentation. During the same period the skin and choroidal melanophores in the ACTH to the culture medium had no effect on depigmentation. The mechanisms of depigmentation in the goldfish are discussed."} {"id": "PMID:162933", "title": "An effect of accumulated matrix on sulfation among cells in a cartilage colony: an autoradiographic study.", "content": "In this report an autoradiographic approach is used to compare synthetic activities of cells within differentiated cartilage colonies. While amino acid incorporation is umiform throughout the colony, H-3-uridine is incorporated more actively by cells having little matrix, cells which are typically in the peripheral regions of a colony. On the other hand S-35-O4 is incorporated most actively by cells in the colony centers. This difference in sulfation appears to occur independently of the mitotic state of the cells, since it is apparent in both growing and near-stationary cultures. Instead, there is a correlation between the accumulation of extracellular matrix and more active levels of sulfation. In support of the idea that matrix creates a microenvironment more favorable to chondrogenesis is the observation that a brief treatment with hyaluronidase, which removes about 60% of the S-35-O4 from prelabeled cultures, depresses isolation of labeled glycosaminoglycans. The possible role of extracellular matrices in altering the expression of differentiated functions by creating a more favorable microenvironment is considered.", "contents": "An effect of accumulated matrix on sulfation among cells in a cartilage colony: an autoradiographic study. In this report an autoradiographic approach is used to compare synthetic activities of cells within differentiated cartilage colonies. While amino acid incorporation is umiform throughout the colony, H-3-uridine is incorporated more actively by cells having little matrix, cells which are typically in the peripheral regions of a colony. On the other hand S-35-O4 is incorporated most actively by cells in the colony centers. This difference in sulfation appears to occur independently of the mitotic state of the cells, since it is apparent in both growing and near-stationary cultures. Instead, there is a correlation between the accumulation of extracellular matrix and more active levels of sulfation. In support of the idea that matrix creates a microenvironment more favorable to chondrogenesis is the observation that a brief treatment with hyaluronidase, which removes about 60% of the S-35-O4 from prelabeled cultures, depresses isolation of labeled glycosaminoglycans. The possible role of extracellular matrices in altering the expression of differentiated functions by creating a more favorable microenvironment is considered."} {"id": "PMID:162939", "title": "Projections of extraocular, neck muscle, and retinal afferents to superior colliculus in the cat: their connections to cells of origin of tectospinal tract.", "content": "Unit recordings were made in the superior colliculus of cats anesthetized with chloralose and with Pentothal. Electrical stimulation of extraocular muscle afferents and neck muscle afferents excited more units in the superior colliculus than did a variety of moving and stationary visual stimuli. Units responding to neck muscle afferent stimulation fell into three populations; one population firing with a short latency and following stimulus presentation up to 1/s, a second population with a long latency and following stimulus presentation at frequencies lower than 15/min, and a third population exhibiting paired firing. The latencies and firing patterns of the third population combined the characteristics of each of the first two patterns. It is suggested that these characteristics of unit discharges stem from the existence of two pathways from neck muscle afferents to the superior colliculus. The projection is predominantly bilateral. Units responding to neck muscle afferent stimulation are distributed throughout the superior colliculus on the basis of their latencies. Long-latency responses predominate in the superficial layers of the superior colliculus and short-latency responses, while more common in the intermediate and deep layers, predominate in the tegmentum. Extraocular muscle afferent projections to the superior colliculus constitute the single richest projection found in these experiments. While the response patterns and latencies are similar to those of the neck muscle afferents, long-latency responses are the most common and dominate in all collicular regions. Few units in the tegmentum could be excited by extraocular muscle afferents. Both extraocular muscle and neck muscle afferents show considerable convergence with one another and with retinal afferents within the superior colliculus. Cells of origin of the tectospinal tract were identified within the superior colliculus and tegmentum by antidromic excitation from the upper cervical cord. These cells were distributed predominantly within the intermediate and deep layers of the superior colliculus, and sparsely in the superficial layers and tegmentum. Almost 50% of the cells of origin of the tectospinal tract receive a convergent input from extraocular muscle and neck muscle afferents and from the retina. About 30% of the cells were inexcitable to the stimuli employed in these experiments. The significance of these projections is discussed with respect to superior collicular function in the cat and i", "contents": "Projections of extraocular, neck muscle, and retinal afferents to superior colliculus in the cat: their connections to cells of origin of tectospinal tract. Unit recordings were made in the superior colliculus of cats anesthetized with chloralose and with Pentothal. Electrical stimulation of extraocular muscle afferents and neck muscle afferents excited more units in the superior colliculus than did a variety of moving and stationary visual stimuli. Units responding to neck muscle afferent stimulation fell into three populations; one population firing with a short latency and following stimulus presentation up to 1/s, a second population with a long latency and following stimulus presentation at frequencies lower than 15/min, and a third population exhibiting paired firing. The latencies and firing patterns of the third population combined the characteristics of each of the first two patterns. It is suggested that these characteristics of unit discharges stem from the existence of two pathways from neck muscle afferents to the superior colliculus. The projection is predominantly bilateral. Units responding to neck muscle afferent stimulation are distributed throughout the superior colliculus on the basis of their latencies. Long-latency responses predominate in the superficial layers of the superior colliculus and short-latency responses, while more common in the intermediate and deep layers, predominate in the tegmentum. Extraocular muscle afferent projections to the superior colliculus constitute the single richest projection found in these experiments. While the response patterns and latencies are similar to those of the neck muscle afferents, long-latency responses are the most common and dominate in all collicular regions. Few units in the tegmentum could be excited by extraocular muscle afferents. Both extraocular muscle and neck muscle afferents show considerable convergence with one another and with retinal afferents within the superior colliculus. Cells of origin of the tectospinal tract were identified within the superior colliculus and tegmentum by antidromic excitation from the upper cervical cord. These cells were distributed predominantly within the intermediate and deep layers of the superior colliculus, and sparsely in the superficial layers and tegmentum. Almost 50% of the cells of origin of the tectospinal tract receive a convergent input from extraocular muscle and neck muscle afferents and from the retina. About 30% of the cells were inexcitable to the stimuli employed in these experiments. The significance of these projections is discussed with respect to superior collicular function in the cat and i"} {"id": "PMID:162940", "title": "Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves.", "content": "The responses of spinothalamic tract neurons were studied by extra- and intracellular recordings from the lumbosacral spinal cord in anesthetized rhesus monkeys (Macaca mulatta). The neurons were identified by antidromic activation from the contralateral diencephalon. They were then classified by the mildest form of mechanical stimulation applied to the ipsilateral hindlimb. The effects of electrical stimulation of the nerve(s) supplying the receptive field were investigated. Graded electrical stimulation revealed that the threshold responses of spinothalamic tract neurons excited by weak mechanical stimuli occurred when the largest afferent fibers were activated. On the other hand, neurons that required intense mechanical stimulation for their excitation tended to have higher thresholds to electrical stimulation. Some spinothalamic tract cells were shown to receive monosynaptic excitatory connections from peripheral nerve fibers, although polysynaptic connections may generally be more important. An input from unmyelinated afferent fibers was demonstrated. It is concluded the primate spinothalamic tract neurons receive a rich convergent input from a variety of cutaneous receptors. The experiments provide some evidence for the most likely types of receptors.", "contents": "Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves. The responses of spinothalamic tract neurons were studied by extra- and intracellular recordings from the lumbosacral spinal cord in anesthetized rhesus monkeys (Macaca mulatta). The neurons were identified by antidromic activation from the contralateral diencephalon. They were then classified by the mildest form of mechanical stimulation applied to the ipsilateral hindlimb. The effects of electrical stimulation of the nerve(s) supplying the receptive field were investigated. Graded electrical stimulation revealed that the threshold responses of spinothalamic tract neurons excited by weak mechanical stimuli occurred when the largest afferent fibers were activated. On the other hand, neurons that required intense mechanical stimulation for their excitation tended to have higher thresholds to electrical stimulation. Some spinothalamic tract cells were shown to receive monosynaptic excitatory connections from peripheral nerve fibers, although polysynaptic connections may generally be more important. An input from unmyelinated afferent fibers was demonstrated. It is concluded the primate spinothalamic tract neurons receive a rich convergent input from a variety of cutaneous receptors. The experiments provide some evidence for the most likely types of receptors."} {"id": "PMID:162941", "title": "Role of monkey precentral cortex in control of voluntary jaw movements.", "content": "Monkeys were trained to produce a low, steady biting force for 0.5-2.5 s, and then a rapid forceful bite in response to a visual stimulus. After large bilateral lesions of the precentral face area, monkeys emitted repetitive forceful bites on the apparatus, but could not perform the force-holding task. They eventually relearned the task, but the force exerted was never as steady as it was prelesion, and often oscillated at about 2 and/or 5-6 Hz. After retraining, two animals with large bilateral lesions of the face area produced median RT responses equal to or only slightly longer than their prelesion performance, indicating that neural pathways not involving the precentral cortex can mediate quick visual RT responses. The variability of RTs was permanently increased, probably as a result of the persistent unsteadiness of the force-holding response. Incomplete bilateral lesions of the precentral face area, a complete unilateral lesion of that area, and bilateral lesions adjacent regions of cortex produced either mild, transient difficulties with the biting taks, or no problems at all. The results indicate that the precentral cortex has a role in the control of voluntary jaw movements. Lesions caused difficulty in controlling, but not producing, closing jaw movements, thereby suggesting that this role is predominantly to inhibit jaw-closing motoneurons or the systems that excite them. Electrical stimulation studies of the face area of the precentral cortex of the unanesthetized monkey point to the same conclusion.", "contents": "Role of monkey precentral cortex in control of voluntary jaw movements. Monkeys were trained to produce a low, steady biting force for 0.5-2.5 s, and then a rapid forceful bite in response to a visual stimulus. After large bilateral lesions of the precentral face area, monkeys emitted repetitive forceful bites on the apparatus, but could not perform the force-holding task. They eventually relearned the task, but the force exerted was never as steady as it was prelesion, and often oscillated at about 2 and/or 5-6 Hz. After retraining, two animals with large bilateral lesions of the face area produced median RT responses equal to or only slightly longer than their prelesion performance, indicating that neural pathways not involving the precentral cortex can mediate quick visual RT responses. The variability of RTs was permanently increased, probably as a result of the persistent unsteadiness of the force-holding response. Incomplete bilateral lesions of the precentral face area, a complete unilateral lesion of that area, and bilateral lesions adjacent regions of cortex produced either mild, transient difficulties with the biting taks, or no problems at all. The results indicate that the precentral cortex has a role in the control of voluntary jaw movements. Lesions caused difficulty in controlling, but not producing, closing jaw movements, thereby suggesting that this role is predominantly to inhibit jaw-closing motoneurons or the systems that excite them. Electrical stimulation studies of the face area of the precentral cortex of the unanesthetized monkey point to the same conclusion."} {"id": "PMID:162942", "title": "A neurophysiological analysis of commissural projections to dentate gyrus of the rat.", "content": "The electrophysiological properties of the commissural projections to the dentate gyrus of the rat were investigated using extracellular field-potential and unit-recording techniques. The following conclusions with respect to those investigations were obtained: 1) The CA3c/CA4 region of the contralateral hippocampus proved to be the most effective site for eliciting the commissural field potentials in the dentate gyrus dorsal and ventral leaves. 2) The location of the short-latency negative field potential in the molecular layer of the dentate gyrus was restricted to a region 50-100 mum distal to the granule cell layers corresponding to the inner one-third of the granule cell dendrites. 3) The negative field potential proved to satisfy a number of criteria for the extracellular representation of the summed EPSPs of synchronously activated granule cells. 4) The excitatory nature of the commissural projections to the dentate was confirmed by the short-latency driving of units recorded from the granule cell layers. 5) A comparison of both commissural and entorhinal cortical stimulation procedures showed the field potentials elicited by the different convergent anatomical systems to be localized within different regions of the dentate molecular layer. 6) The distribution of commissural potentials along the septotemporal axis of the dentate gyrus indicated that stimulation sites homotopic to the recording electrode in the contralateral CA3c/CA4 region were the most effective in eliciting these potentials. 7) These findings were discussed with reference to the mode of activation of the dentate granule cells by the commissural system with specific comparison to the larger and apparently more powerful projections from the entorhinal cortex.", "contents": "A neurophysiological analysis of commissural projections to dentate gyrus of the rat. The electrophysiological properties of the commissural projections to the dentate gyrus of the rat were investigated using extracellular field-potential and unit-recording techniques. The following conclusions with respect to those investigations were obtained: 1) The CA3c/CA4 region of the contralateral hippocampus proved to be the most effective site for eliciting the commissural field potentials in the dentate gyrus dorsal and ventral leaves. 2) The location of the short-latency negative field potential in the molecular layer of the dentate gyrus was restricted to a region 50-100 mum distal to the granule cell layers corresponding to the inner one-third of the granule cell dendrites. 3) The negative field potential proved to satisfy a number of criteria for the extracellular representation of the summed EPSPs of synchronously activated granule cells. 4) The excitatory nature of the commissural projections to the dentate was confirmed by the short-latency driving of units recorded from the granule cell layers. 5) A comparison of both commissural and entorhinal cortical stimulation procedures showed the field potentials elicited by the different convergent anatomical systems to be localized within different regions of the dentate molecular layer. 6) The distribution of commissural potentials along the septotemporal axis of the dentate gyrus indicated that stimulation sites homotopic to the recording electrode in the contralateral CA3c/CA4 region were the most effective in eliciting these potentials. 7) These findings were discussed with reference to the mode of activation of the dentate granule cells by the commissural system with specific comparison to the larger and apparently more powerful projections from the entorhinal cortex."} {"id": "PMID:162943", "title": "Parametric studies of dorsal horn neurons responding to tactile stimulation.", "content": "Dorsal horn neurons responding to tactile input were recorded in segments L3-S2 of unanesthetized, low-spinal cats. Single units were characterized with regard to receptive field (RF) location, RF size and shape, spontaneous discharge rate, central delay, and convergence of four tactile afferent types. 1. RF size increased from the toes to the calf region. 2. Length-width ratio increased from the toes to the calf and declined from the calf to the hip. 3. The relation between RF size and position on the limb was independent of segmental and laminar location of the neurons. 4. RF size was positively correlated with spontaneous discharge rate. 5. The relation between RF size and shape and RF position can be interpreted in terms of regional variations in the magnitude of the gradient of representation in the dorsal horn somatotopic map. 6. Central delay was negatively correlated with both RF size and rate of ongoing discharge. 7. There were no statistically significant differences among the laminae with respect to central delay, RF size or shape, ongoing discharge, or convergence combinations of the four tactile afferent systems. 8. Data presented were at variance with Wall's laminar cascading model for laminae IV-VI. Our results suggest that the model should be modified, at least to emphasize monosynaptic tactile input to all three of these laminae.", "contents": "Parametric studies of dorsal horn neurons responding to tactile stimulation. Dorsal horn neurons responding to tactile input were recorded in segments L3-S2 of unanesthetized, low-spinal cats. Single units were characterized with regard to receptive field (RF) location, RF size and shape, spontaneous discharge rate, central delay, and convergence of four tactile afferent types. 1. RF size increased from the toes to the calf region. 2. Length-width ratio increased from the toes to the calf and declined from the calf to the hip. 3. The relation between RF size and position on the limb was independent of segmental and laminar location of the neurons. 4. RF size was positively correlated with spontaneous discharge rate. 5. The relation between RF size and shape and RF position can be interpreted in terms of regional variations in the magnitude of the gradient of representation in the dorsal horn somatotopic map. 6. Central delay was negatively correlated with both RF size and rate of ongoing discharge. 7. There were no statistically significant differences among the laminae with respect to central delay, RF size or shape, ongoing discharge, or convergence combinations of the four tactile afferent systems. 8. Data presented were at variance with Wall's laminar cascading model for laminae IV-VI. Our results suggest that the model should be modified, at least to emphasize monosynaptic tactile input to all three of these laminae."} {"id": "PMID:162944", "title": "Progressive changes in kitten striate cortex during monocular vision.", "content": "Following initial rearing in either total darkness or normal illumination, kittens at different ages were subjected to right-eye closure and various periods of vision through the left eye. After the period of monocular vision, single units in striate cortex were tested for visual responsiveness through each eye. A severe reduction in the proportion of units responsive to the deprived eye occurred over the first few days of monocular vision. Functional abnormalities were variably present after 1 day, marked after 2.5 and 3.5 days, and complete after 10 days. Monocular vision produced very much the same effect on ocular dominance of striate units, provided age and duration of suture were identical, regardless of whether kittens had received prior dark- or light-rearing.", "contents": "Progressive changes in kitten striate cortex during monocular vision. Following initial rearing in either total darkness or normal illumination, kittens at different ages were subjected to right-eye closure and various periods of vision through the left eye. After the period of monocular vision, single units in striate cortex were tested for visual responsiveness through each eye. A severe reduction in the proportion of units responsive to the deprived eye occurred over the first few days of monocular vision. Functional abnormalities were variably present after 1 day, marked after 2.5 and 3.5 days, and complete after 10 days. Monocular vision produced very much the same effect on ocular dominance of striate units, provided age and duration of suture were identical, regardless of whether kittens had received prior dark- or light-rearing."} {"id": "PMID:162945", "title": "Nonspiking interneurons in walking system of the cockroach.", "content": "Intracellular recordings were made from the neurites of interneurons and motoneurons in the metathoracic ganglion of the cockroach, Periplaneta americana. Many neurons were penetrated which failed to produce action potentials on the application of large depolarizing currents. Nevertheless, some of them strongly excited and/or inhibited slow motoneurons innervating leg musculature, even with weak depolariziing musculature, even with weak depolarizing currents. Cobalt-sulfide-straining of these nonspiking neurons showed them to be interneurons with their neurites contained entirely within the metathoracic ganglion. Two further characteristics of these interneurons were rapid spontaneous fluctuations in membrane potential and a low resting membrane potential. One nonspiking neuron, interneuron I, when depolarized caused a strong excitation of the set of slow levator motoneurons which discharge in bursts during stepping movements of the metathoracic leg. During rhythmic leg movements the membrane potential of interneuron I oscillated with the depolarizing phases occurring at the same time as bursts of activity in the levator motorneurons. No spiking or any other nonspiking neuron was penetrated which could excite these levator motoneurons. From all these observations we conclude that oscillations in the membrane potential of interneuron I are entirely responsible for producing the levator bursts, and thus for producing stepping movements in a walking animal. During rhythmic leg movements, bursts of activity in levator and depressor motoneurons are initiated by slow graded depolarizations. The similarity of the synaptic activity in these two types of motoneurons suggests that burst activity in the depressor motoneurons is also produced by rhythmic activity in nonspiking interneurons. The fact that no spiking neuron was found to excite the depressor motoneurons supports this conclusion. Interneuron I is also an element of the rhythm-generating system, since short depolarizing pulses applied to it during rhythmic activity could reset the thythm. Long-duration current pulses applied to interneuron I in a quiescent animal did not produce rhythmic activity. This observation, together with the finding that during rhythmic activity the slow depolarizations in interneuron I are usually terminated by IPSPs, suggests that interneuron I alone does not generate the rhythm. No spiking interneurons have yet been enccountered which influence the activity in levator motoneurons. Thus, we conclude that the rhythm is generated in a network of nonspiking interneurons. The cellular mechanisms for generating the oscillations in this network are unknown. Continued.", "contents": "Nonspiking interneurons in walking system of the cockroach. Intracellular recordings were made from the neurites of interneurons and motoneurons in the metathoracic ganglion of the cockroach, Periplaneta americana. Many neurons were penetrated which failed to produce action potentials on the application of large depolarizing currents. Nevertheless, some of them strongly excited and/or inhibited slow motoneurons innervating leg musculature, even with weak depolariziing musculature, even with weak depolarizing currents. Cobalt-sulfide-straining of these nonspiking neurons showed them to be interneurons with their neurites contained entirely within the metathoracic ganglion. Two further characteristics of these interneurons were rapid spontaneous fluctuations in membrane potential and a low resting membrane potential. One nonspiking neuron, interneuron I, when depolarized caused a strong excitation of the set of slow levator motoneurons which discharge in bursts during stepping movements of the metathoracic leg. During rhythmic leg movements the membrane potential of interneuron I oscillated with the depolarizing phases occurring at the same time as bursts of activity in the levator motorneurons. No spiking or any other nonspiking neuron was penetrated which could excite these levator motoneurons. From all these observations we conclude that oscillations in the membrane potential of interneuron I are entirely responsible for producing the levator bursts, and thus for producing stepping movements in a walking animal. During rhythmic leg movements, bursts of activity in levator and depressor motoneurons are initiated by slow graded depolarizations. The similarity of the synaptic activity in these two types of motoneurons suggests that burst activity in the depressor motoneurons is also produced by rhythmic activity in nonspiking interneurons. The fact that no spiking neuron was found to excite the depressor motoneurons supports this conclusion. Interneuron I is also an element of the rhythm-generating system, since short depolarizing pulses applied to it during rhythmic activity could reset the thythm. Long-duration current pulses applied to interneuron I in a quiescent animal did not produce rhythmic activity. This observation, together with the finding that during rhythmic activity the slow depolarizations in interneuron I are usually terminated by IPSPs, suggests that interneuron I alone does not generate the rhythm. No spiking interneurons have yet been enccountered which influence the activity in levator motoneurons. Thus, we conclude that the rhythm is generated in a network of nonspiking interneurons. The cellular mechanisms for generating the oscillations in this network are unknown. Continued."} {"id": "PMID:162946", "title": "Technetium-99m-pyrophosphate kinetics and imaging in metabolic bone disease.", "content": "A study was undertaken to investigate the behavior of 99mTc-Sn-pyrophosphate complex in metabolic bone disease. Of clinical importance was the generalized increased periarticular bone accumulation of the radiopharmaceutical in osteomalacia and in combined osteomalacia and osteitis fibrosa as found in patients with chronic renal failure. The pattern in primary hyperparathyroidism was variable. There was no correlation between the initial rates of accumulation of the radiophosphate complex or its bone to soft-tissue uptake ratio at 5 hr when compared with the degree of osteomalacia and osteitis fibrosa. It is postulated that the 99mTc-Sn-pyrophosphate complex has greater affinity for immature collagen than the crystal surface.", "contents": "Technetium-99m-pyrophosphate kinetics and imaging in metabolic bone disease. A study was undertaken to investigate the behavior of 99mTc-Sn-pyrophosphate complex in metabolic bone disease. Of clinical importance was the generalized increased periarticular bone accumulation of the radiopharmaceutical in osteomalacia and in combined osteomalacia and osteitis fibrosa as found in patients with chronic renal failure. The pattern in primary hyperparathyroidism was variable. There was no correlation between the initial rates of accumulation of the radiophosphate complex or its bone to soft-tissue uptake ratio at 5 hr when compared with the degree of osteomalacia and osteitis fibrosa. It is postulated that the 99mTc-Sn-pyrophosphate complex has greater affinity for immature collagen than the crystal surface."} {"id": "PMID:162947", "title": "Technetium-99m-pyrophosphate: studies in vivo and in vitro.", "content": "In rats with induced rickets, the uptake of 99mTcO4 and 99mTc-pyrophosphate per gram of bone was increased as compared with weight-matched controls. However, the uptake of radioactive calcium and 32P-pyrophosphate was similar in both rachitic and control animals, suggesting that the 99mTc label conferred specificity and favored the rachitic lesions. Employing the rat tibia in an in vitro system, 99mTcO4 uptake was predominantly in the organic bone matrix; radioactive calcium, 32P-pyrophosphate, or 14C-diphosphonate uptake was mainly in the bone mineral; and 99mTc-pyrophosphate, 99mTc-diphosphonate, and 99mTc-polyphosphate were found in both mineral and organic phases. By removal of both mineral and polysaccharide and by using agents that altered the degree of collagen fibril cross-linking, evidence was obtained suggesting the 99mTcO4 and 99mTc-pyrophosphate are preferentially bound by immature collagen.", "contents": "Technetium-99m-pyrophosphate: studies in vivo and in vitro. In rats with induced rickets, the uptake of 99mTcO4 and 99mTc-pyrophosphate per gram of bone was increased as compared with weight-matched controls. However, the uptake of radioactive calcium and 32P-pyrophosphate was similar in both rachitic and control animals, suggesting that the 99mTc label conferred specificity and favored the rachitic lesions. Employing the rat tibia in an in vitro system, 99mTcO4 uptake was predominantly in the organic bone matrix; radioactive calcium, 32P-pyrophosphate, or 14C-diphosphonate uptake was mainly in the bone mineral; and 99mTc-pyrophosphate, 99mTc-diphosphonate, and 99mTc-polyphosphate were found in both mineral and organic phases. By removal of both mineral and polysaccharide and by using agents that altered the degree of collagen fibril cross-linking, evidence was obtained suggesting the 99mTcO4 and 99mTc-pyrophosphate are preferentially bound by immature collagen."} {"id": "PMID:162948", "title": "Distribution of 99mTc-Sn diphosphonate and free 99mTc-pertechnetate in selected soft and hard tissues.", "content": "Because increased uptake of 99mTc-diphosphonate (ethane-hydroxy-1, 1-diphosphonate) occasionally occurs in the anterior neck region, the possible increased affinity of the diphosphonate bone-scanning agent for cartilage was investigated. In vivo scintigraphic studies and organ analyses from rats and rabbits injected with this bone scintigraphic agent were performed. Trachea-to-muscle uptake ratios were a high 45:1 in adult Sprague-Dawley rats and approached the femur-to-muscle ratio of 93:1. Technetium-99m-diphosphonate uptake was also increased, but to a lesser extent, in xiphoid cartilage, tendon, and ear cartilage; this was proportional to the calcium content of the organ. The thyroid showed a high affinity for free pertechnetate but not 99mTc-diphosphonate, providing further evidence that the increased neck uptake of this 99mTc-diphosphonate is due to tracheal, not thyroid activity. In addition, premedication of three patients with 200 mg of potassium-perchlorate did not block this neck uptake. Interpretation of scintigraphs performed with 99mTc-diphosphonate that show lesions in the cervical spine should take into account the potential for false-positive readings caused by this increased tracheal uptake.", "contents": "Distribution of 99mTc-Sn diphosphonate and free 99mTc-pertechnetate in selected soft and hard tissues. Because increased uptake of 99mTc-diphosphonate (ethane-hydroxy-1, 1-diphosphonate) occasionally occurs in the anterior neck region, the possible increased affinity of the diphosphonate bone-scanning agent for cartilage was investigated. In vivo scintigraphic studies and organ analyses from rats and rabbits injected with this bone scintigraphic agent were performed. Trachea-to-muscle uptake ratios were a high 45:1 in adult Sprague-Dawley rats and approached the femur-to-muscle ratio of 93:1. Technetium-99m-diphosphonate uptake was also increased, but to a lesser extent, in xiphoid cartilage, tendon, and ear cartilage; this was proportional to the calcium content of the organ. The thyroid showed a high affinity for free pertechnetate but not 99mTc-diphosphonate, providing further evidence that the increased neck uptake of this 99mTc-diphosphonate is due to tracheal, not thyroid activity. In addition, premedication of three patients with 200 mg of potassium-perchlorate did not block this neck uptake. Interpretation of scintigraphs performed with 99mTc-diphosphonate that show lesions in the cervical spine should take into account the potential for false-positive readings caused by this increased tracheal uptake."} {"id": "PMID:162949", "title": "Kinetics of 99mTc-labeled pyrophosphate and polyphosphate in man.", "content": "Thekinetic of 99mTc-labeled pyrophosphate were compared with those of polyphosphate in ten patients in a combined study. Both agents cleared from the blood in a biexpoential fashion. The clearance half-time of Exponent I was the same for both and was shorter than the clearance half-time of Exponent ii. Urinary excretion of both agents was the same during the first hour but during the next 3 hr Tc-pyrophosphate cleared at a slightly more rapid rate, resulting in lower blood background radioactivity. Both agents were bound loosely to plasma proteins, mainly to globulin fractions. The sensitivity of lesion detection was similar for both. Excellent bone images were obtained with both agents. The images with Tc-pyrophosphatewere consistently superior owing to the low blood background and they took less time to accumulate an identical number of counts from identical regions. With the amount of 99mTc-complex used, no hyocalcemia or tetany was noted, nor was there any significant effect on 1-hr serum levels of inorganic phosphours and alkaline phosphatase. Four hours after injection, 9.5% of the dose of Tc-pyrophosphate was circulating in blood, 31.7% was excreted in urine, and the remaining 58.8% was taken up by bone and other tissues. The corresponding values with Tc-polyphosphate were 12.5% in blood, 29.0% in urine, and 58.5% in bone and other tissues. Among the soft tissues, the genitourinary system is most consistently visualized. It is concluded that both Tc-pyroposphate and Tc-polyphosphate are excellent skeletal-imaging agents and that Tc-pyrophosphate appears slightly superior to Tc-polyphosphate.", "contents": "Kinetics of 99mTc-labeled pyrophosphate and polyphosphate in man. Thekinetic of 99mTc-labeled pyrophosphate were compared with those of polyphosphate in ten patients in a combined study. Both agents cleared from the blood in a biexpoential fashion. The clearance half-time of Exponent I was the same for both and was shorter than the clearance half-time of Exponent ii. Urinary excretion of both agents was the same during the first hour but during the next 3 hr Tc-pyrophosphate cleared at a slightly more rapid rate, resulting in lower blood background radioactivity. Both agents were bound loosely to plasma proteins, mainly to globulin fractions. The sensitivity of lesion detection was similar for both. Excellent bone images were obtained with both agents. The images with Tc-pyrophosphatewere consistently superior owing to the low blood background and they took less time to accumulate an identical number of counts from identical regions. With the amount of 99mTc-complex used, no hyocalcemia or tetany was noted, nor was there any significant effect on 1-hr serum levels of inorganic phosphours and alkaline phosphatase. Four hours after injection, 9.5% of the dose of Tc-pyrophosphate was circulating in blood, 31.7% was excreted in urine, and the remaining 58.8% was taken up by bone and other tissues. The corresponding values with Tc-polyphosphate were 12.5% in blood, 29.0% in urine, and 58.5% in bone and other tissues. Among the soft tissues, the genitourinary system is most consistently visualized. It is concluded that both Tc-pyroposphate and Tc-polyphosphate are excellent skeletal-imaging agents and that Tc-pyrophosphate appears slightly superior to Tc-polyphosphate."} {"id": "PMID:162950", "title": "Radiocolloid scans in evaluating splenic response to external radiation.", "content": "By use of 99mTc-sulfur colloid, splenic size as well as liver/spleen ratio of ratioactivity was determined after external radiation of the abdomen. In six patients receiving about 2,000 R whole-abdominal radiation, there was no atrophy of the spleen or abnormal distribution in the liver/spleen ratio of radioactivity (that is, the spleen was still functional). Serial studies in a 7-year-old boy with acute lymphoblastic leukemia in remission showed that 1,450 R splenic radiation did not result in any appreciable change in the length of the organ. In a woman with lymphosarcoma, a change in spleen size did not occur until a dose of 1,800 R was delivered. Another patient had apparently normal uptake of radiocolloid 5 years after 3,600 R. Hence the normal spleen and the spleen affected by other diseases may be far more resistant to external radiation than the spleen diseased with chronic myelocytic leukemia. Spleen scans can be useful in documenting the response of the organ to radiation.", "contents": "Radiocolloid scans in evaluating splenic response to external radiation. By use of 99mTc-sulfur colloid, splenic size as well as liver/spleen ratio of ratioactivity was determined after external radiation of the abdomen. In six patients receiving about 2,000 R whole-abdominal radiation, there was no atrophy of the spleen or abnormal distribution in the liver/spleen ratio of radioactivity (that is, the spleen was still functional). Serial studies in a 7-year-old boy with acute lymphoblastic leukemia in remission showed that 1,450 R splenic radiation did not result in any appreciable change in the length of the organ. In a woman with lymphosarcoma, a change in spleen size did not occur until a dose of 1,800 R was delivered. Another patient had apparently normal uptake of radiocolloid 5 years after 3,600 R. Hence the normal spleen and the spleen affected by other diseases may be far more resistant to external radiation than the spleen diseased with chronic myelocytic leukemia. Spleen scans can be useful in documenting the response of the organ to radiation."} {"id": "PMID:162951", "title": "Distributions of several agents useful in imaging myocardial infarcts.", "content": "Myocardial cell death due to infarction is accompanied by an influx of calcium ion. The calcium ion seems to localize in crystalline structures that form within mitochondria and resemble hydroxyapatite. Based on this phenomenon 99mTc-stannous pyrophosphate has been successfully used to image myocardial infarcts within 24 hr of infarction and 1 hr following tracer administration both in dogs and patient volunteers. In this report, canine distribution studies of 99m-Tc-pyrophosphate are compared with similar studies with 99mTc-stannous polyphosphate, 99mTc-stannous 1, hydroxy-ethylidene-1, 1-disodium phosphonate diphosphonate), and 18F as sodium fluoride. Pyrophosphate polyphosphate, and diphosphonate are each potentially useful in myocardial infarct imaging but bone uptake of 18F occurs sufficiently early to prevent the use of this radionuclide in infarct scintigraphy.", "contents": "Distributions of several agents useful in imaging myocardial infarcts. Myocardial cell death due to infarction is accompanied by an influx of calcium ion. The calcium ion seems to localize in crystalline structures that form within mitochondria and resemble hydroxyapatite. Based on this phenomenon 99mTc-stannous pyrophosphate has been successfully used to image myocardial infarcts within 24 hr of infarction and 1 hr following tracer administration both in dogs and patient volunteers. In this report, canine distribution studies of 99m-Tc-pyrophosphate are compared with similar studies with 99mTc-stannous polyphosphate, 99mTc-stannous 1, hydroxy-ethylidene-1, 1-disodium phosphonate diphosphonate), and 18F as sodium fluoride. Pyrophosphate polyphosphate, and diphosphonate are each potentially useful in myocardial infarct imaging but bone uptake of 18F occurs sufficiently early to prevent the use of this radionuclide in infarct scintigraphy."} {"id": "PMID:162952", "title": "Significance of renewal asymmetry in bone scans: experience in 795 cases.", "content": "A retrospective study of 795 consecutive bone scans employing either 18F or 99mTc-pyrophosphate to evaluate the diagnostic value of renal asymmetry in such scans has been carried out. It is concluded that asymmetric renal images in bone scans convey relatively specific information regarding renal pathology, especially in the 99mTc-pyrophosphate studies.", "contents": "Significance of renewal asymmetry in bone scans: experience in 795 cases. A retrospective study of 795 consecutive bone scans employing either 18F or 99mTc-pyrophosphate to evaluate the diagnostic value of renal asymmetry in such scans has been carried out. It is concluded that asymmetric renal images in bone scans convey relatively specific information regarding renal pathology, especially in the 99mTc-pyrophosphate studies."} {"id": "PMID:162953", "title": "Studies in type I glycogenosis: the paradoxical effect of ethanol on lactate.", "content": "Paradoxically, ethanol, which raises lactate in normal individuals, lowers the elevated levels of lactate in patients with Type I glycogenosis. We found that, although lactate levels fell, pyruvate proportionately declined even more, resulting in an increased L/P ratio which indicates that, as in the normal, the oxidation of ethanol had generated NADH. In type I glycogenosis, the increased level of pyruvate-lactate derives from glycogenolysis. We found that, despite continued glycogenolysis, ethanol had caused less pyruvate-lactate to form. The effect of an increased NADH/NAD+ ratio on the flow of carbon through the Embden-Meyerhof pathway could account for the finding, presumably by its effect on the oxidation-reduction couples with diversion of carbon toward formation of triglyceride rather than pyruvate-lactate.", "contents": "Studies in type I glycogenosis: the paradoxical effect of ethanol on lactate. Paradoxically, ethanol, which raises lactate in normal individuals, lowers the elevated levels of lactate in patients with Type I glycogenosis. We found that, although lactate levels fell, pyruvate proportionately declined even more, resulting in an increased L/P ratio which indicates that, as in the normal, the oxidation of ethanol had generated NADH. In type I glycogenosis, the increased level of pyruvate-lactate derives from glycogenolysis. We found that, despite continued glycogenolysis, ethanol had caused less pyruvate-lactate to form. The effect of an increased NADH/NAD+ ratio on the flow of carbon through the Embden-Meyerhof pathway could account for the finding, presumably by its effect on the oxidation-reduction couples with diversion of carbon toward formation of triglyceride rather than pyruvate-lactate."} {"id": "PMID:162954", "title": "Glycerol intolerance in a child with intermittent hypoglycemia.", "content": "A 3-yr-old boy was investigated for numerous episodes of fatigue, irritability, pallor, and sweating, which began at 11 mo of age, when he had an episode of symptomatic hypoglycemia with ketonuria. He had euphoria, mental confusion, drowsiness, nausea, and vomiting 1-5 hr after oral administration of glycerol in doses of 0.5-1.0gm/kg. Orally administered MCT (1 gm/kg) had similar effects. On one occasion, oral glycerol also provoked hypoglycemia, as had a 16 1/2 hr fast. Intravenously administered glycerol (0.09 gm/kg) induced an immediate loss of consciousness from which he recovered spontaneously after 30 min; there were no changes in blood glucose values. Intravenously administered fructose (0.25 gm/kg) was tolerated normally. Leukocytes showed normal activities for FDPase, glycerol kinase, and glycerol phosphate dehydrogenase. The restriction of dietary intake of fat has been associated with a marked improvement in physical and mental activities. These observations suggest a unique, yet undifined intolerance to glycerol, which suggest caution in the diagnostic use of glycerol in the investigation of hypoglycemia as well as in the therapy of increased intracranial or intraocular pressure.", "contents": "Glycerol intolerance in a child with intermittent hypoglycemia. A 3-yr-old boy was investigated for numerous episodes of fatigue, irritability, pallor, and sweating, which began at 11 mo of age, when he had an episode of symptomatic hypoglycemia with ketonuria. He had euphoria, mental confusion, drowsiness, nausea, and vomiting 1-5 hr after oral administration of glycerol in doses of 0.5-1.0gm/kg. Orally administered MCT (1 gm/kg) had similar effects. On one occasion, oral glycerol also provoked hypoglycemia, as had a 16 1/2 hr fast. Intravenously administered glycerol (0.09 gm/kg) induced an immediate loss of consciousness from which he recovered spontaneously after 30 min; there were no changes in blood glucose values. Intravenously administered fructose (0.25 gm/kg) was tolerated normally. Leukocytes showed normal activities for FDPase, glycerol kinase, and glycerol phosphate dehydrogenase. The restriction of dietary intake of fat has been associated with a marked improvement in physical and mental activities. These observations suggest a unique, yet undifined intolerance to glycerol, which suggest caution in the diagnostic use of glycerol in the investigation of hypoglycemia as well as in the therapy of increased intracranial or intraocular pressure."} {"id": "PMID:162956", "title": "Multiple cerebral abscesses complicating hepatopulmonary amebiasis.", "content": "A 3-year-old boy with hepatopulmonary amebiasis treated with chloroquine phosphate for 20 days subsequently was found to have three brain abscesses and responded to prolonged combined therapy with metronidazole and chloroquine phosphate. Cerebral amebiasis should be considered in any patient with amebic dysentery, hepatic abscess, or pulmonary involvement in whom signs or symptoms of central nervous system involvement appear. A prolonged course of appropriate therapy with periodic brain scanning for evidence of improvement is suggested.", "contents": "Multiple cerebral abscesses complicating hepatopulmonary amebiasis. A 3-year-old boy with hepatopulmonary amebiasis treated with chloroquine phosphate for 20 days subsequently was found to have three brain abscesses and responded to prolonged combined therapy with metronidazole and chloroquine phosphate. Cerebral amebiasis should be considered in any patient with amebic dysentery, hepatic abscess, or pulmonary involvement in whom signs or symptoms of central nervous system involvement appear. A prolonged course of appropriate therapy with periodic brain scanning for evidence of improvement is suggested."} {"id": "PMID:162962", "title": "Endocrinological findings in sterile pink-eyed mice.", "content": "Mice homozygous for rho-25h, a mutation at the pink-eye locus, are small, nervous and male sterile, with abnormal sperm morphology: females have very low fecundity. Evidence is presented that in both sexes the pars nervosa of the rho-25h/rho-25h pituitary contains degenerating nerve axons, that the hypothalamus has a reduced binding capacity for oestradiol-17 beta and that thyroid iodine binding is reduced. No changes were observed in the anterior pituitary. In rho-25h/rho-25h females, the uterus is threas-like and unresponsive to oestradiol, and the ovaries are small with many abnormal follicles. Possible modes of action of the rho locus are duscussed with reference to this and pre-existing data on the rho phenotype.", "contents": "Endocrinological findings in sterile pink-eyed mice. Mice homozygous for rho-25h, a mutation at the pink-eye locus, are small, nervous and male sterile, with abnormal sperm morphology: females have very low fecundity. Evidence is presented that in both sexes the pars nervosa of the rho-25h/rho-25h pituitary contains degenerating nerve axons, that the hypothalamus has a reduced binding capacity for oestradiol-17 beta and that thyroid iodine binding is reduced. No changes were observed in the anterior pituitary. In rho-25h/rho-25h females, the uterus is threas-like and unresponsive to oestradiol, and the ovaries are small with many abnormal follicles. Possible modes of action of the rho locus are duscussed with reference to this and pre-existing data on the rho phenotype."} {"id": "PMID:162963", "title": "A review of tumor antigens in gynecologic malignancies.", "content": "Evidence for the presence of tumor-associated gynecologic tumor antigens from our laboratory and others is presented. Tumor-associated antigens have been described for invasive carcinoma of the cervix and mucinous carcinoma of the ovary with cross-reacting antigens in malignant vulvar tissue. The provocative finding of a cross-reacting antigen in malignant cervical, vulvar and ovarian tissue raises the possibility of a common etiologic agent. The hope of the clinician is to utilize the tumor antigens in diagnosis and therapy. However, it is necessary to caution against overzealous acceptance so the carcinoembryonic antigen story is not repeated.", "contents": "A review of tumor antigens in gynecologic malignancies. Evidence for the presence of tumor-associated gynecologic tumor antigens from our laboratory and others is presented. Tumor-associated antigens have been described for invasive carcinoma of the cervix and mucinous carcinoma of the ovary with cross-reacting antigens in malignant vulvar tissue. The provocative finding of a cross-reacting antigen in malignant cervical, vulvar and ovarian tissue raises the possibility of a common etiologic agent. The hope of the clinician is to utilize the tumor antigens in diagnosis and therapy. However, it is necessary to caution against overzealous acceptance so the carcinoembryonic antigen story is not repeated."} {"id": "PMID:162964", "title": "Minimal growth requirements for Clostridium perfringens and isolation of auxotrophic mutants.", "content": "The minimal growth requirements for two strains of Clostridium perfringens were defined, and both synthetic and semisynthetic plating media were developed. Plate counts of the wild-type strains on both of these minimal media were equivalent to those on complex media. A number of auxotrophic mutants of each strain were isolated, and their phenotypes were defined.", "contents": "Minimal growth requirements for Clostridium perfringens and isolation of auxotrophic mutants. The minimal growth requirements for two strains of Clostridium perfringens were defined, and both synthetic and semisynthetic plating media were developed. Plate counts of the wild-type strains on both of these minimal media were equivalent to those on complex media. A number of auxotrophic mutants of each strain were isolated, and their phenotypes were defined."} {"id": "PMID:162965", "title": "Recovery of murine leukemia virus from large volumes of freshly harvested culture fluids by using a single density gradient.", "content": "Concentration and purification of murine leukemia virus for use as complement fixation antigens was accomplished by using a single density gradient in the model RK ultracentrifuge.", "contents": "Recovery of murine leukemia virus from large volumes of freshly harvested culture fluids by using a single density gradient. Concentration and purification of murine leukemia virus for use as complement fixation antigens was accomplished by using a single density gradient in the model RK ultracentrifuge."} {"id": "PMID:162966", "title": "Septic and crystalline joint disease. A simultaneous occurrence.", "content": "Bacteria and crystals were simultaneously recovered from the synovial fluid of two patients with acutely inflamed joints. The bacteria were initially identified on Gram stain and subsequently grown on supplemented peptone broth, and the crystals were readily identified by polarizing microscopy. Although cause-and-effect relationship between these two types of arthritis cannot be established, the need for thorough examination of synovial fluid is evident.", "contents": "Septic and crystalline joint disease. A simultaneous occurrence. Bacteria and crystals were simultaneously recovered from the synovial fluid of two patients with acutely inflamed joints. The bacteria were initially identified on Gram stain and subsequently grown on supplemented peptone broth, and the crystals were readily identified by polarizing microscopy. Although cause-and-effect relationship between these two types of arthritis cannot be established, the need for thorough examination of synovial fluid is evident."} {"id": "PMID:162974", "title": "Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism.", "content": "Clinical and laboratory evaluations are reported on two patients with congenital goiter and hypothyroidism due to iodide organification defect. In one patient, a 31-year-old white male with severe mental retardation, administration of perchlorate caused discharge of 69% of the radioiodine accumulated in the thyroid gland. Thyroid tissue had negligible peroxidase activity in the tyrosine-iodinase, triliodide, and guaiacol assays. Preincubation of subcellular fractions with hematin restored activity. The restored enzyme was labile to high concentrations of H2O2 (5.6times 10-4 h2o2 produced inhibition in the triiodide assay). Heating of the enzyme for 5 min at 46 degrees C produced 50% inactivation, while higher temperatures were required to half-inactivate normal peroxidases. This case represents a second example of the \"peroxidase apoenzyme-prosthetic group defect\" causing congenital goiter. The second patient, an example of the \"deficient peroxidase defect,\" was a 10-yr-old girl with 35% discharge of thyroidal radioiodine by perchlorate. Peroxidase activity in the goiter tissue was quantitatively decreased (10%-20% of normal values) but kinetically normal with respect to apparent Km for H2O2. Hematin had little effect on the enzyme. Peroxidase activity had abnormal subcellular distribution, since pellets sedimenting between 39,000 and 105,000 g contained most of the activity. Normal thyroglobulin was observed in the thyroid gland of the patient. Two distinct defects of the peroxidase system can produce congenital goiter by limiting organification of iodide.", "contents": "Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism. Clinical and laboratory evaluations are reported on two patients with congenital goiter and hypothyroidism due to iodide organification defect. In one patient, a 31-year-old white male with severe mental retardation, administration of perchlorate caused discharge of 69% of the radioiodine accumulated in the thyroid gland. Thyroid tissue had negligible peroxidase activity in the tyrosine-iodinase, triliodide, and guaiacol assays. Preincubation of subcellular fractions with hematin restored activity. The restored enzyme was labile to high concentrations of H2O2 (5.6times 10-4 h2o2 produced inhibition in the triiodide assay). Heating of the enzyme for 5 min at 46 degrees C produced 50% inactivation, while higher temperatures were required to half-inactivate normal peroxidases. This case represents a second example of the \"peroxidase apoenzyme-prosthetic group defect\" causing congenital goiter. The second patient, an example of the \"deficient peroxidase defect,\" was a 10-yr-old girl with 35% discharge of thyroidal radioiodine by perchlorate. Peroxidase activity in the goiter tissue was quantitatively decreased (10%-20% of normal values) but kinetically normal with respect to apparent Km for H2O2. Hematin had little effect on the enzyme. Peroxidase activity had abnormal subcellular distribution, since pellets sedimenting between 39,000 and 105,000 g contained most of the activity. Normal thyroglobulin was observed in the thyroid gland of the patient. Two distinct defects of the peroxidase system can produce congenital goiter by limiting organification of iodide."} {"id": "PMID:163004", "title": "Primary Epstein-Barr-virus infections in acute neurologic diseases.", "content": "Infectious mononucleosis has been associated with Guillain--Barr\u00e9 syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.", "contents": "Primary Epstein-Barr-virus infections in acute neurologic diseases. Infectious mononucleosis has been associated with Guillain--Barr\u00e9 syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis."} {"id": "PMID:163015", "title": "Long-term steroid therapy in patients with adrenogenital syndrome.", "content": "Fifteen years' experience with the adrenogenital syndrome at Duke University Medical Center is reviewed. Twenty-six patients were diagnosed before age 2. Of these, 20 had the salt-losing syndrome. The complications encountered and the results obtained in terms of growth, developemnt, and fertility are discussed. Delay in diagnosis and inappropriate gender assignment continue to be a problem.", "contents": "Long-term steroid therapy in patients with adrenogenital syndrome. Fifteen years' experience with the adrenogenital syndrome at Duke University Medical Center is reviewed. Twenty-six patients were diagnosed before age 2. Of these, 20 had the salt-losing syndrome. The complications encountered and the results obtained in terms of growth, developemnt, and fertility are discussed. Delay in diagnosis and inappropriate gender assignment continue to be a problem."} {"id": "PMID:163016", "title": "Adrenal virilism due to 21-hydroxylase deficiency in the postmenarchial female.", "content": "Five new patients with postmenarchial onset of adrenal virilism related to 21-hydroxylase deficiency are presented. Diagnostic criteria are reviewed. Four pregnancies resulting in 3 term infants occurred after instigation of therapy. Eleven patients similar in clinical presentation are reviewed for comparison. Findings of value in distinguishing these two groups of patients are discussed.", "contents": "Adrenal virilism due to 21-hydroxylase deficiency in the postmenarchial female. Five new patients with postmenarchial onset of adrenal virilism related to 21-hydroxylase deficiency are presented. Diagnostic criteria are reviewed. Four pregnancies resulting in 3 term infants occurred after instigation of therapy. Eleven patients similar in clinical presentation are reviewed for comparison. Findings of value in distinguishing these two groups of patients are discussed."} {"id": "PMID:163017", "title": "Paget's disease of the vulva: a clinicopathologic study of eight cases.", "content": "Clinicopatholigic findings in 8 patients with Paget's disease of the vulva are presented with a discussion if its pathogenesis. In 7 cases the disease was intraepithelial, and in 1 it was accompanied by underlying adenocarcinoma. The treatment of choice is surgical. The importance of early diagnosis, adequate excision, and close followup is emphasized. In 2 cases, the disease was associated with carcinoma of the breast and in 1 case with carcinoma of the liver.", "contents": "Paget's disease of the vulva: a clinicopathologic study of eight cases. Clinicopatholigic findings in 8 patients with Paget's disease of the vulva are presented with a discussion if its pathogenesis. In 7 cases the disease was intraepithelial, and in 1 it was accompanied by underlying adenocarcinoma. The treatment of choice is surgical. The importance of early diagnosis, adequate excision, and close followup is emphasized. In 2 cases, the disease was associated with carcinoma of the breast and in 1 case with carcinoma of the liver."} {"id": "PMID:163024", "title": "Dynamic scintigraphy of primary and secondary malignant intracranial neoplasms.", "content": "Dynamic images and arteriograms were reviewed in patients with proved primary and secondary malignant intracranial neoplasms. In 44% of the patients with glioblastomas and 23% of those with metastatic lesions, radioactivity appeared early in the dynamic imaging sequence. This was related to the presence of arteriovenous shunting on arteriography rather than to a tumor stain. Neither characteristic dynamic imaging patterns nor rapid arteriovenous shunting was seen in patients with astrocytomas.", "contents": "Dynamic scintigraphy of primary and secondary malignant intracranial neoplasms. Dynamic images and arteriograms were reviewed in patients with proved primary and secondary malignant intracranial neoplasms. In 44% of the patients with glioblastomas and 23% of those with metastatic lesions, radioactivity appeared early in the dynamic imaging sequence. This was related to the presence of arteriovenous shunting on arteriography rather than to a tumor stain. Neither characteristic dynamic imaging patterns nor rapid arteriovenous shunting was seen in patients with astrocytomas."} {"id": "PMID:163025", "title": "Experience with 111-In-chloride scanning in patients with focal defects on 99-mTc-sulfur colloid liver scans.", "content": "Thirty-nine patients with focal defects on the technetium liver scan were rescanned using 111-In chloride. Of 20 patients with hepatic malignancy, 11 had positive indium scans. None of the 19 with focal cirrhotic fibrosis had a positive indium scan although 5 of these had primary tumor. Thus, a positive indium scan suggests that the defect is malignant. A negative indium scan is less helpful, failling to distinguish between neoplasm and focal cirrhosis. Positive uptake in an extrahepatic primary neoplasm and negative uptake in the liver suggest that the hepatic lesion is not neoplastic.", "contents": "Experience with 111-In-chloride scanning in patients with focal defects on 99-mTc-sulfur colloid liver scans. Thirty-nine patients with focal defects on the technetium liver scan were rescanned using 111-In chloride. Of 20 patients with hepatic malignancy, 11 had positive indium scans. None of the 19 with focal cirrhotic fibrosis had a positive indium scan although 5 of these had primary tumor. Thus, a positive indium scan suggests that the defect is malignant. A negative indium scan is less helpful, failling to distinguish between neoplasm and focal cirrhosis. Positive uptake in an extrahepatic primary neoplasm and negative uptake in the liver suggest that the hepatic lesion is not neoplastic."} {"id": "PMID:163026", "title": "Irradiated lung cancer. An autopsy analysis of spread pattern.", "content": "The spread pattern was studied in 48 autopsied cases of irradiated, apparently localized lung cancer. Disease was found in the upper abdomen in 52%, in the brain in 8.7%; in the bones in 20.8%; and confined to the thoracic cavity in 27%. Radical irradiation controlled 38% locally. The pattern of metastasis in these irradiated lung tumors did not seem to differ from that of unirradiated lung cancers reported elsewhere.", "contents": "Irradiated lung cancer. An autopsy analysis of spread pattern. The spread pattern was studied in 48 autopsied cases of irradiated, apparently localized lung cancer. Disease was found in the upper abdomen in 52%, in the brain in 8.7%; in the bones in 20.8%; and confined to the thoracic cavity in 27%. Radical irradiation controlled 38% locally. The pattern of metastasis in these irradiated lung tumors did not seem to differ from that of unirradiated lung cancers reported elsewhere."} {"id": "PMID:163027", "title": "Carcinoma associated with irradiation of the immature breast.", "content": "In two women who had undergone radiation therapy at ages one and eleven years, respectively, carcinoma in a hypoplastic breast developed. Each patient was treated by radical mastectomy. One patient is presently being followed without evidence of metastases; the other died of sarcoidosis following thoracotomy. A history of irradiation, hypoplasia and microscopic findings compatible with radiation changes suggests that these two cases of carcinoma may be radiation-induced.", "contents": "Carcinoma associated with irradiation of the immature breast. In two women who had undergone radiation therapy at ages one and eleven years, respectively, carcinoma in a hypoplastic breast developed. Each patient was treated by radical mastectomy. One patient is presently being followed without evidence of metastases; the other died of sarcoidosis following thoracotomy. A history of irradiation, hypoplasia and microscopic findings compatible with radiation changes suggests that these two cases of carcinoma may be radiation-induced."} {"id": "PMID:163035", "title": "The inheritance of mild Type II hyperlipoproteinaemia.", "content": "The distribution of plasma total and low density lipoprotein cholesterol concentration was investigated in 158 first degree relatives (105 progeny, 53 siblings) of 55 index patients with mild type II hyperlipoproteinaemia. No evidence of bimodality was found. Our findings support the view that mild type II hyperlipoproteinaemia is inherited in a polygenic manner.", "contents": "The inheritance of mild Type II hyperlipoproteinaemia. The distribution of plasma total and low density lipoprotein cholesterol concentration was investigated in 158 first degree relatives (105 progeny, 53 siblings) of 55 index patients with mild type II hyperlipoproteinaemia. No evidence of bimodality was found. Our findings support the view that mild type II hyperlipoproteinaemia is inherited in a polygenic manner."} {"id": "PMID:163036", "title": "Adenosine 3',5'-monophosphate analogs promote a circular morphology of cultured Schwannoma cells.", "content": "Dibutyryl adenosine 3',5'-monophosphate (dibutyrl cycle AMP) and 8-bromo cyclic AMP stimulated cells cultured from a rat Schwannoma to change their morphology from irregularly shaped to flattened circular and hollow circular forms within 30 minutes. The change in shape was specifically effected by analogs of cyclic AMP and cyclic AMP elevating agents, was reversible after removal of these additives, and was prevented by vinblastine and cytochalasin b, but was not affected by actinomycin D or cycloheximide.", "contents": "Adenosine 3',5'-monophosphate analogs promote a circular morphology of cultured Schwannoma cells. Dibutyryl adenosine 3',5'-monophosphate (dibutyrl cycle AMP) and 8-bromo cyclic AMP stimulated cells cultured from a rat Schwannoma to change their morphology from irregularly shaped to flattened circular and hollow circular forms within 30 minutes. The change in shape was specifically effected by analogs of cyclic AMP and cyclic AMP elevating agents, was reversible after removal of these additives, and was prevented by vinblastine and cytochalasin b, but was not affected by actinomycin D or cycloheximide."} {"id": "PMID:163037", "title": "Reduced incidence of spontaneous mammary tumors in C3H/He mice after treatment with polyadenylate-polyuridylate.", "content": "The effect of treatment with the double-stranded polynucleotide complex polydenylate with polyuridylate [poly(A) with poly(U)] on tumor development in C3H/He mice was evaluated. Poly(A) with poly(U) was injected in newborn females, and mice were observed for 380 days. During this experimental period 42 percent of treated mice developed tumors, while the incidence in the control group was 63 percent. This difference was statistically significant.", "contents": "Reduced incidence of spontaneous mammary tumors in C3H/He mice after treatment with polyadenylate-polyuridylate. The effect of treatment with the double-stranded polynucleotide complex polydenylate with polyuridylate [poly(A) with poly(U)] on tumor development in C3H/He mice was evaluated. Poly(A) with poly(U) was injected in newborn females, and mice were observed for 380 days. During this experimental period 42 percent of treated mice developed tumors, while the incidence in the control group was 63 percent. This difference was statistically significant."} {"id": "PMID:163038", "title": "Collagenase production by lymphokine-activated macrophages.", "content": "Macrophages incubated with products (lymphokines) secreted by stimulated spleen cells produced collagenase. Active lymphokines were obtained both from mitogen- and antigen-stimulated lymphocytes. These observations suggest that the degradation of collagen in chronic inflammatory lesions may be caused by macrophage collagenase.", "contents": "Collagenase production by lymphokine-activated macrophages. Macrophages incubated with products (lymphokines) secreted by stimulated spleen cells produced collagenase. Active lymphokines were obtained both from mitogen- and antigen-stimulated lymphocytes. These observations suggest that the degradation of collagen in chronic inflammatory lesions may be caused by macrophage collagenase."} {"id": "PMID:163039", "title": "Endogenous cyclic adenosine monophosphate in tissues of rabbits fed an atherogenic diet.", "content": "Rabbits fed a high cholesterol diet experienced a significant increase in plasma adenosine 3,5-monophosphate (cyclic AMP), which was simultaneous with the increase in plasma cholesterol. The content of cyclic AMP in atherosclerotic lesion areas of rabbit aortic intima-media was significantly higher (0.24 picomole per microgram of DNA) than that in adjacent nonlesion areas or in aortic intima-dedia from control animals (0.09 picomole per microgram of DNA). The cyclic AMP content of heart, liver, skeletal muscle, and diaphragm showed no significant elevation in animals fed cholesterol.", "contents": "Endogenous cyclic adenosine monophosphate in tissues of rabbits fed an atherogenic diet. Rabbits fed a high cholesterol diet experienced a significant increase in plasma adenosine 3,5-monophosphate (cyclic AMP), which was simultaneous with the increase in plasma cholesterol. The content of cyclic AMP in atherosclerotic lesion areas of rabbit aortic intima-media was significantly higher (0.24 picomole per microgram of DNA) than that in adjacent nonlesion areas or in aortic intima-dedia from control animals (0.09 picomole per microgram of DNA). The cyclic AMP content of heart, liver, skeletal muscle, and diaphragm showed no significant elevation in animals fed cholesterol."} {"id": "PMID:163042", "title": "Characterization of a nuclear receptor for testosterone in rat bone marrow.", "content": "In vitro testosterone binding was studied in a nuclear extract (0.15 M KC1) from rat bone marrow using the charcoal assay. The nuclear extract contains binding sites saturable at low concentration of testosterone (1 times 10-8M). From a Scatchard plot of the data obtained it is concluded that a single class of receptor sites is involved in the binding of testosterone. Studies indicated that the testosterone-nuclear complex has a dissociation constant (Kd) of 5.9 times 10-9 M binding 9 times 10-14 moles/mg nuclear protein. 5alpha- and 5beta-dihydrotestosterone compete poorly with testosterone for binding sites in the nuclear component while estradiol -17beta does not compete at all. The protein nature of the receptor was demonstrated and an isoelectric point (pI) of 4.9 was determined for the complex by the use of isoelectric focusing.", "contents": "Characterization of a nuclear receptor for testosterone in rat bone marrow. In vitro testosterone binding was studied in a nuclear extract (0.15 M KC1) from rat bone marrow using the charcoal assay. The nuclear extract contains binding sites saturable at low concentration of testosterone (1 times 10-8M). From a Scatchard plot of the data obtained it is concluded that a single class of receptor sites is involved in the binding of testosterone. Studies indicated that the testosterone-nuclear complex has a dissociation constant (Kd) of 5.9 times 10-9 M binding 9 times 10-14 moles/mg nuclear protein. 5alpha- and 5beta-dihydrotestosterone compete poorly with testosterone for binding sites in the nuclear component while estradiol -17beta does not compete at all. The protein nature of the receptor was demonstrated and an isoelectric point (pI) of 4.9 was determined for the complex by the use of isoelectric focusing."} {"id": "PMID:163043", "title": "A manganese catalyzed covalent binding of estradiol - 17 beta to cytosol proteins of rabbit uterus.", "content": "Studies of the temperature sensitivity of estradiol receptor binding in rabbit uterine cytosol have revealed the existence of an enzyme which catalyzes the covalent binding of estradiol to cytosol proteins. A fraction, prepared by chromatography on Biogel P-200 and incubated at 37 degrees C in the presence of Mn++, exhibited a time-dependent, temperature-sensitive, oxidative binding of estradiol not seen in the crude cytosol preparation. Although the activity of this enzyme was shown to be independent of estradiol binding by the high affinity estrogen receptor, its presence may complicate studies of estrogen receptor action which involve the use of elevated temperatures.", "contents": "A manganese catalyzed covalent binding of estradiol - 17 beta to cytosol proteins of rabbit uterus. Studies of the temperature sensitivity of estradiol receptor binding in rabbit uterine cytosol have revealed the existence of an enzyme which catalyzes the covalent binding of estradiol to cytosol proteins. A fraction, prepared by chromatography on Biogel P-200 and incubated at 37 degrees C in the presence of Mn++, exhibited a time-dependent, temperature-sensitive, oxidative binding of estradiol not seen in the crude cytosol preparation. Although the activity of this enzyme was shown to be independent of estradiol binding by the high affinity estrogen receptor, its presence may complicate studies of estrogen receptor action which involve the use of elevated temperatures."} {"id": "PMID:163056", "title": "Chemical action of influenza virus on the red blood cell membrane. II. Action on membrane lipids and amino acids.", "content": "Haemagglutination by influenza virus strains PR8 and Lee as well as treatment of red blood cells by periodate produced numerous and manifold changes in the lipids and the amino acid composition of the erythrocytes. The changes induced by the influenza strains differed from each other and from those induced by periodate. Alterations in the membrane lipids observed after haemagglutination by heat treated strain PR8 and by its native form were identical.", "contents": "Chemical action of influenza virus on the red blood cell membrane. II. Action on membrane lipids and amino acids. Haemagglutination by influenza virus strains PR8 and Lee as well as treatment of red blood cells by periodate produced numerous and manifold changes in the lipids and the amino acid composition of the erythrocytes. The changes induced by the influenza strains differed from each other and from those induced by periodate. Alterations in the membrane lipids observed after haemagglutination by heat treated strain PR8 and by its native form were identical."} {"id": "PMID:163057", "title": "The effect of supraoptimal temperature on the multiplication of different cytomegalovirus strains.", "content": "The virion synthesis by five human cytomegalovirus (CMV) strains in human embryonic fibroblast cultures was stopped by incubation of the infected cultures at 40 degrees C. At this temperature the antigens appeared diffusely filling the nucleus and the cytoplasm. The blocking effect of the elevated temperature was exerted in the same period of the reproduction cycle as the inhibitory effect of cytosine arabinoside (ara-C). In cell cultures infected with CMV and incubated first at 40 degrees C, then at 37 degrees C, the synthesis of infectious virus started again, thus the abortive cycle developed at 40 degrees C was reversible. The inhibition of virus multiplication cannot be attributed to the thermosensitive events in the normal function of the host cell.", "contents": "The effect of supraoptimal temperature on the multiplication of different cytomegalovirus strains. The virion synthesis by five human cytomegalovirus (CMV) strains in human embryonic fibroblast cultures was stopped by incubation of the infected cultures at 40 degrees C. At this temperature the antigens appeared diffusely filling the nucleus and the cytoplasm. The blocking effect of the elevated temperature was exerted in the same period of the reproduction cycle as the inhibitory effect of cytosine arabinoside (ara-C). In cell cultures infected with CMV and incubated first at 40 degrees C, then at 37 degrees C, the synthesis of infectious virus started again, thus the abortive cycle developed at 40 degrees C was reversible. The inhibition of virus multiplication cannot be attributed to the thermosensitive events in the normal function of the host cell."} {"id": "PMID:163058", "title": "Chemical action of influenza virus on the red blood cell membrane. I. Action on membrane neuraminic acids.", "content": "The chemical action of influenza virus strains PR8 and Lee and of periodate on the neuraminic acid containing lipids of human red blood cells has been investigated by thin layer chromatography. The results showed that haemagglutination by the two strains as well as periodate treatment induced manifold and profound chemical alterations in the neuraminic acid-containing lipids. The changes produced by strains PR8 and Lee differed from each other and from those caused by periodate. Alterations in the neuraminic acid-containing lipids induced by heated strain PR8 were identical with those obtained after haemagglutination by the native virus, indicating that virus neuraminidase is not inactivated by heat. Thus, differences in the haemagglutinating ability between native and heated virus are not due to enzyme inactivation.", "contents": "Chemical action of influenza virus on the red blood cell membrane. I. Action on membrane neuraminic acids. The chemical action of influenza virus strains PR8 and Lee and of periodate on the neuraminic acid containing lipids of human red blood cells has been investigated by thin layer chromatography. The results showed that haemagglutination by the two strains as well as periodate treatment induced manifold and profound chemical alterations in the neuraminic acid-containing lipids. The changes produced by strains PR8 and Lee differed from each other and from those caused by periodate. Alterations in the neuraminic acid-containing lipids induced by heated strain PR8 were identical with those obtained after haemagglutination by the native virus, indicating that virus neuraminidase is not inactivated by heat. Thus, differences in the haemagglutinating ability between native and heated virus are not due to enzyme inactivation."} {"id": "PMID:163059", "title": "X-ray diffraction from micrograms of quartz on filters using a rotating anode.", "content": "X-ray diffraction data from samples of 20, 60 and 100 mug quartz on poly-vinyl chloride membrane filters have been collected using a rotating anode x-ray source. These data suggest that 17 mug of quartz or possibly less could be measured directly on 35 mm diameter filters without any type of pretreatment.", "contents": "X-ray diffraction from micrograms of quartz on filters using a rotating anode. X-ray diffraction data from samples of 20, 60 and 100 mug quartz on poly-vinyl chloride membrane filters have been collected using a rotating anode x-ray source. These data suggest that 17 mug of quartz or possibly less could be measured directly on 35 mm diameter filters without any type of pretreatment."} {"id": "PMID:163060", "title": "Identification of nonfermentative gram-negative bacteria in the clinical laboratory.", "content": "A simplified, concise scheme was developed for the identification of nonfermentative, gram-negative bacteria which have most frequently been reported in the literature as definite or possible agents of human disease. These organisms included apyocyanogenic Pseudomonas aeruginosa, P. fluorescens, P. putida, P. stutzeri, P. maltophilia, P. putrefaciens, P. cepacia, P. alcaligenes, FLAVOBACTERIUM SPECIES, Bordetella bronchiseptica, Acinetobacter anitratum (Herellea vaginicola), A. Iwoffi (Mima polymorpha), Moraxella species, Alcaligenes odorans and Alcaligenes species. The tests used for identification included production of cytochrome oxidase, amylase, deoxyribonuclease, gelatinase, urease and Beta-galactosidase; motility; oxidation of one per cent glucose and ten per cent lactose; fluorescence; indole, hydrogen sulfide and nitrogen gas production; denitrification of nitrites; growth at 42C; penicillin sensitivity and production of an aromatic odor and greenish discoloration on blood agar. Using this scheme, 85 per cent of 243 isolates (unknowns and reference strains) were identified to genus and species. Of the 15 per cent remaining, 11 per cent were identified as alkaline organisms and four per cent were unidentifiable.", "contents": "Identification of nonfermentative gram-negative bacteria in the clinical laboratory. A simplified, concise scheme was developed for the identification of nonfermentative, gram-negative bacteria which have most frequently been reported in the literature as definite or possible agents of human disease. These organisms included apyocyanogenic Pseudomonas aeruginosa, P. fluorescens, P. putida, P. stutzeri, P. maltophilia, P. putrefaciens, P. cepacia, P. alcaligenes, FLAVOBACTERIUM SPECIES, Bordetella bronchiseptica, Acinetobacter anitratum (Herellea vaginicola), A. Iwoffi (Mima polymorpha), Moraxella species, Alcaligenes odorans and Alcaligenes species. The tests used for identification included production of cytochrome oxidase, amylase, deoxyribonuclease, gelatinase, urease and Beta-galactosidase; motility; oxidation of one per cent glucose and ten per cent lactose; fluorescence; indole, hydrogen sulfide and nitrogen gas production; denitrification of nitrites; growth at 42C; penicillin sensitivity and production of an aromatic odor and greenish discoloration on blood agar. Using this scheme, 85 per cent of 243 isolates (unknowns and reference strains) were identified to genus and species. Of the 15 per cent remaining, 11 per cent were identified as alkaline organisms and four per cent were unidentifiable."} {"id": "PMID:163061", "title": "Hyperkinetic children: the use of stimulant drugs evaluated.", "content": "Use of stimulant drugs in the treatment of hyperkinetic children is reviewed briefly. While drugs appear to be effective in \"normalizing\" behavior, too little attention has been paid to potential side effects. There is need for a broader program of clinical evaluation, assessing drug effects not only on behavior, but on appetite and the cardiovascular system, and taking into account the sociological impact of drug use by children.", "contents": "Hyperkinetic children: the use of stimulant drugs evaluated. Use of stimulant drugs in the treatment of hyperkinetic children is reviewed briefly. While drugs appear to be effective in \"normalizing\" behavior, too little attention has been paid to potential side effects. There is need for a broader program of clinical evaluation, assessing drug effects not only on behavior, but on appetite and the cardiovascular system, and taking into account the sociological impact of drug use by children."} {"id": "PMID:163062", "title": "Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. I. Penetration of the intestinal epithelium by trophozoites.", "content": "Germ-free guinea pigs were inoculated intracecally with Entamoeba histolytica and the enteric flora derived from a human patient with acute amebic colitis. Aanimals were killed at post-inoculation intervals of 7 to 12 days. The mode of penetration of cecal epithelium by the ameba was examined by light and electron microscopy. The following sequence was reconstructed from numerous individual observations. When the amebae were in moderately close proximity to the brush, border, the microvilli became shortened, irregular, and sometimes disappeared. Dense material was observed between the amebae and microvilli. When the ameba was very close to the epithelium the apical portion of epithelial cytoplasm projected into the lumen contacting the organism, thus becoming detached from adjoining cells. This produced spaces between epithelial cells through which amebae invaded interepithelial spaces. Initially the ameba penetrated the interglandular epithelium. Later, it penetrated equally the glandular and interglandular epithelium barrier. There were marked alterations of cytoplasmic components of epithelial cells. Polymorphonuclear leukocytes migrated into the epithelium filling these spaces; these often showed a variety of degenerative processes. Amebae, utilizing their pseudopodia, moved further through the intercellular spaces and reached the lamina propria.", "contents": "Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. I. Penetration of the intestinal epithelium by trophozoites. Germ-free guinea pigs were inoculated intracecally with Entamoeba histolytica and the enteric flora derived from a human patient with acute amebic colitis. Aanimals were killed at post-inoculation intervals of 7 to 12 days. The mode of penetration of cecal epithelium by the ameba was examined by light and electron microscopy. The following sequence was reconstructed from numerous individual observations. When the amebae were in moderately close proximity to the brush, border, the microvilli became shortened, irregular, and sometimes disappeared. Dense material was observed between the amebae and microvilli. When the ameba was very close to the epithelium the apical portion of epithelial cytoplasm projected into the lumen contacting the organism, thus becoming detached from adjoining cells. This produced spaces between epithelial cells through which amebae invaded interepithelial spaces. Initially the ameba penetrated the interglandular epithelium. Later, it penetrated equally the glandular and interglandular epithelium barrier. There were marked alterations of cytoplasmic components of epithelial cells. Polymorphonuclear leukocytes migrated into the epithelium filling these spaces; these often showed a variety of degenerative processes. Amebae, utilizing their pseudopodia, moved further through the intercellular spaces and reached the lamina propria."} {"id": "PMID:163063", "title": "Chemotherapy of experimental Echinococcus granulosus infection. Trials in CF1 mice and jirds (Meriones unguiculatus).", "content": "Mice and jirds with experimental secondary hydatidosis (Echinococus granulous) were treated at various post-infection periods with eight different drugs; iodinized oil of thymol, ethyl-N-dimethyl ether of thymol fumarate, chloroguanide, rifampin, pentamidine isethionate, amphotericin B, suramin, and methotrexate. In initial experiments with methotrexate, mice treated after 99 days of infection had significantly fewer infections at necropsy than did controls (33% and 100%, respecitively). However, in subsequent studies at three dose levels of methotrexate in mice 10 days after infection and in mice and jirds 240 days post infection, no significant differences were found in the percentage of animals infected, cyst size, or number between treated and control animals. The other drugs tested were similarly without effect under the experimental conditions used.", "contents": "Chemotherapy of experimental Echinococcus granulosus infection. Trials in CF1 mice and jirds (Meriones unguiculatus). Mice and jirds with experimental secondary hydatidosis (Echinococus granulous) were treated at various post-infection periods with eight different drugs; iodinized oil of thymol, ethyl-N-dimethyl ether of thymol fumarate, chloroguanide, rifampin, pentamidine isethionate, amphotericin B, suramin, and methotrexate. In initial experiments with methotrexate, mice treated after 99 days of infection had significantly fewer infections at necropsy than did controls (33% and 100%, respecitively). However, in subsequent studies at three dose levels of methotrexate in mice 10 days after infection and in mice and jirds 240 days post infection, no significant differences were found in the percentage of animals infected, cyst size, or number between treated and control animals. The other drugs tested were similarly without effect under the experimental conditions used."} {"id": "PMID:163064", "title": "Swine buffy coat culture: an aid to the laboratory diagnosis of hog cholera.", "content": "A 2-step technique for the isolation of hog cholera (HC) virus consisting of an initial culture on buffy coat (BC) cultures and subinoculation to a pig kidney cell line (PK-15) was described. By this technique, HC virus was confirmed in specimens from 65 herds in which the conventional cell culture isolation technique failed. The herds were located in 20 states and Puerto Rico. Specimens from 29 of the 65 herds were inoculated into specific-pathogen-free (SPF) pigs. Hog cholera virus was recovered from 27 of the test pigs. The 2 pigs from which virus was not recovered had signs of acute infection and, on necropsy, had gross lesions of HC infection.", "contents": "Swine buffy coat culture: an aid to the laboratory diagnosis of hog cholera. A 2-step technique for the isolation of hog cholera (HC) virus consisting of an initial culture on buffy coat (BC) cultures and subinoculation to a pig kidney cell line (PK-15) was described. By this technique, HC virus was confirmed in specimens from 65 herds in which the conventional cell culture isolation technique failed. The herds were located in 20 states and Puerto Rico. Specimens from 29 of the 65 herds were inoculated into specific-pathogen-free (SPF) pigs. Hog cholera virus was recovered from 27 of the test pigs. The 2 pigs from which virus was not recovered had signs of acute infection and, on necropsy, had gross lesions of HC infection."} {"id": "PMID:163065", "title": "The Tecumseh study of respiratory illness. VIII. Acute infection in chronic respiratory disease and comparison groups.", "content": "Individuals with chronic lung disease and their families were selected from the Tecumsch community along with similarly selected families as comparison groups and studied for 1-year periods. Occurence of acute respiratory illness was ascertained weekly by telephone and calculated as an annual rate. Persons with chronic bronchitis not only experienced more acute lower respiratory illness than healthy comparison subjects, but total illness rates were somewhat higher as well. Infection rates were determined from blood samples taken 3 times from each participant during the surveillance year. Antibody tests were performed for respiratory syncytial virus, para-influenza virus types 1, 2, and 3, influenza types A and B, coronavirus OC43, Mycoplasma pneumoniae, and Haemophilus influenzae. Differences in serologic infection rates among the subgroups of the population were similar to those seen in the clinical data, with more frequent infection among those with bronchitis than among the comparison subjects. This finding indicates that some degree of increased susceptibility to actual infection existed among those individuals with bronchitis. Influence of smoking on illness and infection rates was also examined. Infections were, in general, more frequent in smokers than in nonsmokers, but illness rates were reversed, suggesting that perception of disease differed in the 2 groups. Rates of illness and infection of other adults in the families of the index individuals with bronchitis were not influenced by the higher rates seen in the index individuals; however, it was of interest that children of persons with bronchitis did have somewhat higher rates of infection than children of comparison subjects.", "contents": "The Tecumseh study of respiratory illness. VIII. Acute infection in chronic respiratory disease and comparison groups. Individuals with chronic lung disease and their families were selected from the Tecumsch community along with similarly selected families as comparison groups and studied for 1-year periods. Occurence of acute respiratory illness was ascertained weekly by telephone and calculated as an annual rate. Persons with chronic bronchitis not only experienced more acute lower respiratory illness than healthy comparison subjects, but total illness rates were somewhat higher as well. Infection rates were determined from blood samples taken 3 times from each participant during the surveillance year. Antibody tests were performed for respiratory syncytial virus, para-influenza virus types 1, 2, and 3, influenza types A and B, coronavirus OC43, Mycoplasma pneumoniae, and Haemophilus influenzae. Differences in serologic infection rates among the subgroups of the population were similar to those seen in the clinical data, with more frequent infection among those with bronchitis than among the comparison subjects. This finding indicates that some degree of increased susceptibility to actual infection existed among those individuals with bronchitis. Influence of smoking on illness and infection rates was also examined. Infections were, in general, more frequent in smokers than in nonsmokers, but illness rates were reversed, suggesting that perception of disease differed in the 2 groups. Rates of illness and infection of other adults in the families of the index individuals with bronchitis were not influenced by the higher rates seen in the index individuals; however, it was of interest that children of persons with bronchitis did have somewhat higher rates of infection than children of comparison subjects."} {"id": "PMID:163066", "title": "Roentgenographically atypical Pneumocystis carinii pneumonia.", "content": "Two patients with renal transplants were admitted for evaluation of fever. During the course of hospitalization both had hectic fever and arthralgia. Pulmonary symptoms were absent or minimal. In one patient the admitting chest roentgenogram was entirely normal and in the other only a small focal abnormality was apparent. Hypoxemia occurred even in the presence of normal or nearly normal chest roentgenograms. The diagnosis of Pneumocystis carinii infection was made by bronchoscopic brush biopsy in both patients. Therapy with pentamidine isethionate was successful. It is suggested that in patients with renal transplants and in others with similar immonosuppression, even with a normal chest roentgenogram, Pneumocystis carinii infection be considered as the cause of a fever of unknown origin. This should be evaluated initially with blood gas studies; if these are abnormal, further studies, including biopsy, are justified.", "contents": "Roentgenographically atypical Pneumocystis carinii pneumonia. Two patients with renal transplants were admitted for evaluation of fever. During the course of hospitalization both had hectic fever and arthralgia. Pulmonary symptoms were absent or minimal. In one patient the admitting chest roentgenogram was entirely normal and in the other only a small focal abnormality was apparent. Hypoxemia occurred even in the presence of normal or nearly normal chest roentgenograms. The diagnosis of Pneumocystis carinii infection was made by bronchoscopic brush biopsy in both patients. Therapy with pentamidine isethionate was successful. It is suggested that in patients with renal transplants and in others with similar immonosuppression, even with a normal chest roentgenogram, Pneumocystis carinii infection be considered as the cause of a fever of unknown origin. This should be evaluated initially with blood gas studies; if these are abnormal, further studies, including biopsy, are justified."} {"id": "PMID:163067", "title": "The effects of proteolytic enzymes on the tensile strength of human lung.", "content": "Human lung tissues were exposed to proteolytic enzymes to determine the effects on tensile strength and to clarify the relationship between tensile strength and the amounts of collagen and elastin in the tissue. Elastase and papain depleted the tissue of elastin but failed to alter tensile strength. Trypsin had no effect on tensile strength, or on collagen and elastin content. collagenase lowered tensile strength and reduced the amount of collagen in the tissue. The findings with collagenase were in agreement with measurements in control tissues that showed a direct relationship between tensile strength and collagen content. These results confirm collagen as the principal determinant of the tensile strength of human lung.", "contents": "The effects of proteolytic enzymes on the tensile strength of human lung. Human lung tissues were exposed to proteolytic enzymes to determine the effects on tensile strength and to clarify the relationship between tensile strength and the amounts of collagen and elastin in the tissue. Elastase and papain depleted the tissue of elastin but failed to alter tensile strength. Trypsin had no effect on tensile strength, or on collagen and elastin content. collagenase lowered tensile strength and reduced the amount of collagen in the tissue. The findings with collagenase were in agreement with measurements in control tissues that showed a direct relationship between tensile strength and collagen content. These results confirm collagen as the principal determinant of the tensile strength of human lung."} {"id": "PMID:163068", "title": "Synthesis of factor VIII antigen by cultured human endothelial cells.", "content": "Endothelial cells have been isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical vein and grown in tissue culture. These cells have been identified by morphologic and immunologic criteria. It has been demonstrated that these cultured human endothelial cells synthesize and release factor VIII antigen but not factor VIII clot-promoting activity.", "contents": "Synthesis of factor VIII antigen by cultured human endothelial cells. Endothelial cells have been isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical vein and grown in tissue culture. These cells have been identified by morphologic and immunologic criteria. It has been demonstrated that these cultured human endothelial cells synthesize and release factor VIII antigen but not factor VIII clot-promoting activity."} {"id": "PMID:163069", "title": "Ultrastructural studies of regenerating spines of the sea urchin Strongylocentrotus purpuratus. II. Cell types with spherules.", "content": "The fine structure of spherulecytes, cell types with large, intracellular membrane-bound vacuoles termed spherules, was investigated in regenerating tips of spines of the sea urchin Strongylocentrotus purpuratus. Two categories of cell types were observed: red spherulecytes and colorless spherulecytes. Red spherulecytes were represented by a single cell type, the eleocyte, while colorless spherulecytes consisted of three morphologically distinct cell types termed morula cells, granulocytes, and vacuolecytes. Eleocytes and morula cells were distributed in both the epidermis and dermis, while granulocytes and vacuolecytes were present only in the dermis. After processing for light and electron microscopy, the spherules of eleocytes typically appeared empty, having lost their content of the red pigment, echinochrome. In contrast, the spherules of morula cell, granulocytes, and vacuolecytes enclosed a variety of granular and other material. The cell types reported in this paper resembled, to various degrees, spherulecytes in the coelomic fluid of echinoids described by other investigators.", "contents": "Ultrastructural studies of regenerating spines of the sea urchin Strongylocentrotus purpuratus. II. Cell types with spherules. The fine structure of spherulecytes, cell types with large, intracellular membrane-bound vacuoles termed spherules, was investigated in regenerating tips of spines of the sea urchin Strongylocentrotus purpuratus. Two categories of cell types were observed: red spherulecytes and colorless spherulecytes. Red spherulecytes were represented by a single cell type, the eleocyte, while colorless spherulecytes consisted of three morphologically distinct cell types termed morula cells, granulocytes, and vacuolecytes. Eleocytes and morula cells were distributed in both the epidermis and dermis, while granulocytes and vacuolecytes were present only in the dermis. After processing for light and electron microscopy, the spherules of eleocytes typically appeared empty, having lost their content of the red pigment, echinochrome. In contrast, the spherules of morula cell, granulocytes, and vacuolecytes enclosed a variety of granular and other material. The cell types reported in this paper resembled, to various degrees, spherulecytes in the coelomic fluid of echinoids described by other investigators."} {"id": "PMID:163073", "title": "Cellular structure and function in normal and neoplastic lymphoid cells.", "content": "In general, the ultrastructure of normal lymphocytes and plasma cells reflects their functional state. Similarly, in pathologic conditions, ultrastructural abnormalities may reflect specific functional derangements of the cells. The identification of some structural abnormalities may be clinically useful, even though their origin and biochemical composition is still obscure.", "contents": "Cellular structure and function in normal and neoplastic lymphoid cells. In general, the ultrastructure of normal lymphocytes and plasma cells reflects their functional state. Similarly, in pathologic conditions, ultrastructural abnormalities may reflect specific functional derangements of the cells. The identification of some structural abnormalities may be clinically useful, even though their origin and biochemical composition is still obscure."} {"id": "PMID:163070", "title": "Radionuclide angiography in juvenile angiofibroma of the nasopharynx.", "content": "Radionuclide angiography was performed by intravenous injection of 99mTc-pertechnetate and recorded by serial gamma camera scintiphotographs. Its usefulness as a prebiopsy or preoperative procedure is demonstrated by two case reports of angiofibroma of the nasopharynx and it was also found to be useful for radiation therapy follow-up assessment. Radionuclide angiography offers a convenient and safe method to assess the vascularity of a mass and by this technique the surgeon may be alerted to the possibility of severe postbiopsy hemorrhage and also the occasional dramatic complications of radiological carotid angiography can be avoided.", "contents": "Radionuclide angiography in juvenile angiofibroma of the nasopharynx. Radionuclide angiography was performed by intravenous injection of 99mTc-pertechnetate and recorded by serial gamma camera scintiphotographs. Its usefulness as a prebiopsy or preoperative procedure is demonstrated by two case reports of angiofibroma of the nasopharynx and it was also found to be useful for radiation therapy follow-up assessment. Radionuclide angiography offers a convenient and safe method to assess the vascularity of a mass and by this technique the surgeon may be alerted to the possibility of severe postbiopsy hemorrhage and also the occasional dramatic complications of radiological carotid angiography can be avoided."} {"id": "PMID:163074", "title": "Sleep disturbance in schizophrenia. A revisit.", "content": "Rapid eye movement (REM) sleep mechanisms may play a role in the pathophysiology of schizophrenia, but results have been inconclusive and studies of sleep in schizophrena have been deficient in identifying, comparing, and differentiating between subcategories of schizophrenia. Twenty-nine hospitalized, drug-free schizophrenics were divided into three subgroups\u0101cute, latent, and schizoaffective. The REM intensity measures and REM latency were found to differentiate significantly the schizoaffective group. Sleep-continuity indexes separated the latent and acute groups. Seven patients who later required treatment with tricyclic an tidepressants had base line REM latencies significantly lower and hospitalizations significantly more prolonged than the patients who did not require antidepressants. Sleep measurements may thus identify diagnostic subgroups of schizophrenia as well as predict which schizophrenic depressive syndrome or a concurrent affective syndrome.", "contents": "Sleep disturbance in schizophrenia. A revisit. Rapid eye movement (REM) sleep mechanisms may play a role in the pathophysiology of schizophrenia, but results have been inconclusive and studies of sleep in schizophrena have been deficient in identifying, comparing, and differentiating between subcategories of schizophrenia. Twenty-nine hospitalized, drug-free schizophrenics were divided into three subgroups\u0101cute, latent, and schizoaffective. The REM intensity measures and REM latency were found to differentiate significantly the schizoaffective group. Sleep-continuity indexes separated the latent and acute groups. Seven patients who later required treatment with tricyclic an tidepressants had base line REM latencies significantly lower and hospitalizations significantly more prolonged than the patients who did not require antidepressants. Sleep measurements may thus identify diagnostic subgroups of schizophrenia as well as predict which schizophrenic depressive syndrome or a concurrent affective syndrome."} {"id": "PMID:163071", "title": "Glomus tumors in the head and neck: III. Analysis of clinical manifestations.", "content": "Seventy-five patients with glomus tumors in the head and neck had a 37% incidence of cranial nerve paralysis and a 14.6% incidence of intracranial extension. Jugular foramen syndrome is associated with 50% and hypoglossal nerve involvement with 75% posterior fossa tumor invasion. Horner's syndrome is associated with 50% middle cranial fossa tumor invasion. The incidence of central nervous system (CNS) involvement with cranial NERVE PARALYSIS (NOT INCLUDING VII nerve) is 52%. Otologic findings and VII nerve paralysis did not correlate with tumor resectability, CNS extension, and prognosis.", "contents": "Glomus tumors in the head and neck: III. Analysis of clinical manifestations. Seventy-five patients with glomus tumors in the head and neck had a 37% incidence of cranial nerve paralysis and a 14.6% incidence of intracranial extension. Jugular foramen syndrome is associated with 50% and hypoglossal nerve involvement with 75% posterior fossa tumor invasion. Horner's syndrome is associated with 50% middle cranial fossa tumor invasion. The incidence of central nervous system (CNS) involvement with cranial NERVE PARALYSIS (NOT INCLUDING VII nerve) is 52%. Otologic findings and VII nerve paralysis did not correlate with tumor resectability, CNS extension, and prognosis."} {"id": "PMID:163075", "title": "Congenital herpetic keratitis.", "content": "An infant, the first-born of twins, delivered by cesarean seciton without prior rupture of the membranes, was noted to have an advanced epithellal and stromal keratitis at berth. Herpes simplex, type 1, was cultured form the cornea and from skin vesicles which developed subsequently. The advanced nature of the lesion indicates that it was acquired in utero. This appears to be the first reported case of congential herpetic keratitis.", "contents": "Congenital herpetic keratitis. An infant, the first-born of twins, delivered by cesarean seciton without prior rupture of the membranes, was noted to have an advanced epithellal and stromal keratitis at berth. Herpes simplex, type 1, was cultured form the cornea and from skin vesicles which developed subsequently. The advanced nature of the lesion indicates that it was acquired in utero. This appears to be the first reported case of congential herpetic keratitis."} {"id": "PMID:163072", "title": "Amyotrophic lateral sclerosis. Inclusion bodies in a case of the classic sporadic form.", "content": "Postmortem light and electron microscopic studies of a 52 year old black male who died 17 months after the onset of upper and lower motor neuron signs showed: (1) degeneration of cortico-spinal tracts, (2) loss of spinal neurons and gliosis and (3) cellular inclusions with neurotubules, neurofilaments and granular material. Although these cellular inclusions resemble Lafora bodies, they differ in that, to the authors' knowledge, the latter were not reported to have microtubules. Review of the literature revealed no previous report of these inclusions in cases of amyotrophic lateral sclerosis. Tissue cultures of cord, hindbrain and cerebrum did not show cytopathic effect during a three-week observation period.", "contents": "Amyotrophic lateral sclerosis. Inclusion bodies in a case of the classic sporadic form. Postmortem light and electron microscopic studies of a 52 year old black male who died 17 months after the onset of upper and lower motor neuron signs showed: (1) degeneration of cortico-spinal tracts, (2) loss of spinal neurons and gliosis and (3) cellular inclusions with neurotubules, neurofilaments and granular material. Although these cellular inclusions resemble Lafora bodies, they differ in that, to the authors' knowledge, the latter were not reported to have microtubules. Review of the literature revealed no previous report of these inclusions in cases of amyotrophic lateral sclerosis. Tissue cultures of cord, hindbrain and cerebrum did not show cytopathic effect during a three-week observation period."} {"id": "PMID:163076", "title": "Centronuclear myopathy: histochemistry and electron microscopy. Report of two cases.", "content": "In two new cases of centronuclear myopathy, histochemical findings included failure to differentiate fiber type with oxidative enzymes, the presence of core glycogenosis, and core acid phosphatase activity. Fluorescence microscopy demonstrated autofluorescent lipochrome in fiber centers and nonspecific fiber injury in some immunofluorescent preparations. Electron microscopical findings included the observation of unusually small myofibrils arrayed between central nuclei.", "contents": "Centronuclear myopathy: histochemistry and electron microscopy. Report of two cases. In two new cases of centronuclear myopathy, histochemical findings included failure to differentiate fiber type with oxidative enzymes, the presence of core glycogenosis, and core acid phosphatase activity. Fluorescence microscopy demonstrated autofluorescent lipochrome in fiber centers and nonspecific fiber injury in some immunofluorescent preparations. Electron microscopical findings included the observation of unusually small myofibrils arrayed between central nuclei."} {"id": "PMID:163095", "title": "Functional differences in protein synthesis between rat liver tRNA and tRNA from Novikoff hepatoma.", "content": "Synthesis of ovalbumin in fragmented oviduct magnum explants of immature, estrogen-stimulated chicks has been studied in the presence of exogenous tRNA. tRAN from Novikoff hepatoma specifically inhibited ovalbumin synthesis, determined by precipitation with antisera. In addition, the major protein(s) synthesized in the presence of hepatoma tRNA had higher electrophoretic mobility than ovalbumin, as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis. tRNAs from rat liver, rooster liver, and hen oviduct did not affect ovalbumin synthesis, although oviduct tRNA is stimulatory during the earlier stages of estrogen stimulation.", "contents": "Functional differences in protein synthesis between rat liver tRNA and tRNA from Novikoff hepatoma. Synthesis of ovalbumin in fragmented oviduct magnum explants of immature, estrogen-stimulated chicks has been studied in the presence of exogenous tRNA. tRAN from Novikoff hepatoma specifically inhibited ovalbumin synthesis, determined by precipitation with antisera. In addition, the major protein(s) synthesized in the presence of hepatoma tRNA had higher electrophoretic mobility than ovalbumin, as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis. tRNAs from rat liver, rooster liver, and hen oviduct did not affect ovalbumin synthesis, although oviduct tRNA is stimulatory during the earlier stages of estrogen stimulation."} {"id": "PMID:163096", "title": "Oligonucleotide sequences of pancreatic and T1 ribonuclease digests of 5S ribosomal RNA from mouse cells.", "content": "Oligonucleotides produced by complete pancreatic and T1 RNase digestion of 5S ribosomal RNA from a mouse hepatoma, MH 134, have been separated with two-dimensional electrophoresis and their nucleotide sequences determined. Except for the presence of a 5'-terminal diphosphate, these nucleotide sequences were identical with those of KB cells, confirming the identity of the primary structure of 5S RNA between these animals. Both oligonucleotide patterns produced with these enzymes from 5S RNA of the liver were also identical with those of the hepatoma. All these agree with the strong conservation of 5S RNA genes in animal species. However, when 5S ribosomal RNA was extracted from ribosomes which were prepared from microsomal pellet, pancreatic RNase digest contained two trinucleotides (A-G-Cp and G-A-Cp) that were not found in 5S RNA prepared with a one-step procedure. It was concluded that different isolation procedure might indeed cause artifactual fragments on enzymatic digestion due to internal nicks produced during isolation. The significance of 5'-terminal diphosphate in relation to the biosynthesis of 5S ribosomal RNA is also discussed.", "contents": "Oligonucleotide sequences of pancreatic and T1 ribonuclease digests of 5S ribosomal RNA from mouse cells. Oligonucleotides produced by complete pancreatic and T1 RNase digestion of 5S ribosomal RNA from a mouse hepatoma, MH 134, have been separated with two-dimensional electrophoresis and their nucleotide sequences determined. Except for the presence of a 5'-terminal diphosphate, these nucleotide sequences were identical with those of KB cells, confirming the identity of the primary structure of 5S RNA between these animals. Both oligonucleotide patterns produced with these enzymes from 5S RNA of the liver were also identical with those of the hepatoma. All these agree with the strong conservation of 5S RNA genes in animal species. However, when 5S ribosomal RNA was extracted from ribosomes which were prepared from microsomal pellet, pancreatic RNase digest contained two trinucleotides (A-G-Cp and G-A-Cp) that were not found in 5S RNA prepared with a one-step procedure. It was concluded that different isolation procedure might indeed cause artifactual fragments on enzymatic digestion due to internal nicks produced during isolation. The significance of 5'-terminal diphosphate in relation to the biosynthesis of 5S ribosomal RNA is also discussed."} {"id": "PMID:163097", "title": "Inhibition by cyclic AMP and dibutyryl cyclic AMP of transport of organic acids in kidney cortex.", "content": "1. Cyclic adenosine 3',5'-monophosphate and N-6-2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate decrease the initial entry rate and the steady-state uptake of p-aminohippurate and uric acid by rabbit kidney cortex slices. 2. N-6-2'-O-Dibutyryl adenosine 3'-5'-monophosphate inhibits the tubular transport of p-aminohippurate competitively. 3. Isoproterenol, known to increase cyclic nucleotide concentration of the cortical tubules by activation of adenyl cyclase, decreases p-aminohippurate transport. Antidiuretic hormone which is known to stimulate only medullary adenyl cyclase has no effect on p-amino-hippurate uptake by cortical slices. 4. Theophylline, which inhibits cyclic nucleotide phosphodiesterase and, therefore, enhances the cellular accumulation of endogenous cyclic nucleotide, depresses p-aminohippurate transport.", "contents": "Inhibition by cyclic AMP and dibutyryl cyclic AMP of transport of organic acids in kidney cortex. 1. Cyclic adenosine 3',5'-monophosphate and N-6-2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate decrease the initial entry rate and the steady-state uptake of p-aminohippurate and uric acid by rabbit kidney cortex slices. 2. N-6-2'-O-Dibutyryl adenosine 3'-5'-monophosphate inhibits the tubular transport of p-aminohippurate competitively. 3. Isoproterenol, known to increase cyclic nucleotide concentration of the cortical tubules by activation of adenyl cyclase, decreases p-aminohippurate transport. Antidiuretic hormone which is known to stimulate only medullary adenyl cyclase has no effect on p-amino-hippurate uptake by cortical slices. 4. Theophylline, which inhibits cyclic nucleotide phosphodiesterase and, therefore, enhances the cellular accumulation of endogenous cyclic nucleotide, depresses p-aminohippurate transport."} {"id": "PMID:163098", "title": "Effect of polymyxin B on liposomal membranes derived from Escherichia coli lipids.", "content": "The specificity of the action of polymyxin B was studied using liposomes as a model membrane system. Liposomes prepared from total lipids of Gram-negative bacteria Escherichia coli, a mixture of purified E. coli phosphatidylethanolamine and cardiolipin and a mixture of phosphatidylethanolamine and phosphatidylglycerol, were extemely sensitive to polymyxin while those prepared from lipids of Gram-positive bacteria Streptococcus sanguis, lipids of sheep erythrocyte membranes, mixtures of egg lecithin and negatively charged amphiphatic molecules, were less sensitive to the action of the antibiotic. Cholesterol was shown to suppress the polymyxin-induced response in liposomes.", "contents": "Effect of polymyxin B on liposomal membranes derived from Escherichia coli lipids. The specificity of the action of polymyxin B was studied using liposomes as a model membrane system. Liposomes prepared from total lipids of Gram-negative bacteria Escherichia coli, a mixture of purified E. coli phosphatidylethanolamine and cardiolipin and a mixture of phosphatidylethanolamine and phosphatidylglycerol, were extemely sensitive to polymyxin while those prepared from lipids of Gram-positive bacteria Streptococcus sanguis, lipids of sheep erythrocyte membranes, mixtures of egg lecithin and negatively charged amphiphatic molecules, were less sensitive to the action of the antibiotic. Cholesterol was shown to suppress the polymyxin-induced response in liposomes."} {"id": "PMID:163099", "title": "Magnetic resonance studies on the mitochondrial divalent cation carrier.", "content": "Measurements of water proton spin relaxation enhancements (epsilon) can be used to discriminate high-affinity binding of Mn-2+ or Gd-3+ to biological membranes, from low-affinity binding. In rat liver mitochondria, epsilon b values of approx. 11 are observed upon binding of Mn-2+ to the inner membrane, while internal or low-affinity binding remains invisible to this technique. Energy-driven Mn-2+ uptake by liver mitochondria results in the subsequent decay of epsilon. Comparison of epsilon with the initial velocity of Mn-2+ uptake in rat liver mitochondria reveals a linear correlation, which holds at all temperatures between 0 degrees C and 40 degrees C, regardless of the mitochondrial protein concentration. Consequently, enhancement appears to reflect the binding of Mn-2+ to the divalent cation pump. Binding of Mn-2+ to blowfly flight muscle also results in substantial epsilon, which is associated with the glycerol-1-phosphate dehydrogenase instead of divalent cation transport. Consequently, no decay in epsilon due to uptake occurs after Mn-2+ is bound. Lanthanide ions are also bound and transported by mitochondria. Addition of Gd-3+ to pigeon heart or rat liver mitochondria results in epsilon b approximately equal to 5-6, which decays with similar kinetics in both systems. The uptake velocity of Gd-3+ in rat liver mitochondria is about 1/6 the rate with which Mn-2+ is transported. Lanthanides also diminish epsilon due to the addition of Mn-2+, and greatly retard the Mn-2+ uptake kinetics. The presence of carbonylcyanide-p-trifluoromethoxyphenylhydrazone depresses epsilon upon addition of Mn-2+ or Gd-3+ and also uncouples energy-driven uptake. On the other hand, prolonged anaerobic incubation in the presence of antimycin and rotenone exhausts the mitochondria of their energy stores, blocks the uptake of Mn-2+, but does not affect epsilon significantly. Evidently, the uncoupler-induced disappearance of divalent cation binding sites is not the result of \"de-energization\". Measurements of epsilon at several NMR frequencies indicate a correlation time (tau b) for carrier-bound Mn-2+ in rat liver mitochondria between 20 ns and 4 ns as one varies the temperature between 10 degrees C and 30 degrees C. The 13 Kcal/mole activation energy for tau b suggests that the 11 ns time constant at room temperature represents the movement of the Mn-11-carrier comples. On the other hand, tau b is probably approx. 100 times too short to represent the rotational motion of a carrier protein. Apparently, Mn-2+ binds to a small arm of the carrier which moves independent", "contents": "Magnetic resonance studies on the mitochondrial divalent cation carrier. Measurements of water proton spin relaxation enhancements (epsilon) can be used to discriminate high-affinity binding of Mn-2+ or Gd-3+ to biological membranes, from low-affinity binding. In rat liver mitochondria, epsilon b values of approx. 11 are observed upon binding of Mn-2+ to the inner membrane, while internal or low-affinity binding remains invisible to this technique. Energy-driven Mn-2+ uptake by liver mitochondria results in the subsequent decay of epsilon. Comparison of epsilon with the initial velocity of Mn-2+ uptake in rat liver mitochondria reveals a linear correlation, which holds at all temperatures between 0 degrees C and 40 degrees C, regardless of the mitochondrial protein concentration. Consequently, enhancement appears to reflect the binding of Mn-2+ to the divalent cation pump. Binding of Mn-2+ to blowfly flight muscle also results in substantial epsilon, which is associated with the glycerol-1-phosphate dehydrogenase instead of divalent cation transport. Consequently, no decay in epsilon due to uptake occurs after Mn-2+ is bound. Lanthanide ions are also bound and transported by mitochondria. Addition of Gd-3+ to pigeon heart or rat liver mitochondria results in epsilon b approximately equal to 5-6, which decays with similar kinetics in both systems. The uptake velocity of Gd-3+ in rat liver mitochondria is about 1/6 the rate with which Mn-2+ is transported. Lanthanides also diminish epsilon due to the addition of Mn-2+, and greatly retard the Mn-2+ uptake kinetics. The presence of carbonylcyanide-p-trifluoromethoxyphenylhydrazone depresses epsilon upon addition of Mn-2+ or Gd-3+ and also uncouples energy-driven uptake. On the other hand, prolonged anaerobic incubation in the presence of antimycin and rotenone exhausts the mitochondria of their energy stores, blocks the uptake of Mn-2+, but does not affect epsilon significantly. Evidently, the uncoupler-induced disappearance of divalent cation binding sites is not the result of \"de-energization\". Measurements of epsilon at several NMR frequencies indicate a correlation time (tau b) for carrier-bound Mn-2+ in rat liver mitochondria between 20 ns and 4 ns as one varies the temperature between 10 degrees C and 30 degrees C. The 13 Kcal/mole activation energy for tau b suggests that the 11 ns time constant at room temperature represents the movement of the Mn-11-carrier comples. On the other hand, tau b is probably approx. 100 times too short to represent the rotational motion of a carrier protein. Apparently, Mn-2+ binds to a small arm of the carrier which moves independent"} {"id": "PMID:163100", "title": "Androgen receptors: relationship to growth response and to intracellular androgen transport in nine variant lines of the Shionogi mouse mammary carcinoma.", "content": "Aspects of the biological significance of androgen receptors have been studied in nine variant lines of the Shionogi carcinoma, two of which are androgen dependent and seven of which are autonomous. The dependent lines, and two of the seven autonomous lines, contain androgen receptors; this finding demonstrates that the presence of receptors is not an accurate marker of hormonal dependence in vivo. Since the ability to transport androgens into the nucleus, as judged from the relative maximal rates of transport, is virtually restricted to dependent and autonomous lines which possess cytoplasmic receptors, it is clear that such receptors may play a role in regulating the intranuclear concentration of androgens. The absence of cytoplasmic receptors and the comparative lack of perceptible transfer of androgens across the nuclear membrane are features peculiar to the autonomous condition.", "contents": "Androgen receptors: relationship to growth response and to intracellular androgen transport in nine variant lines of the Shionogi mouse mammary carcinoma. Aspects of the biological significance of androgen receptors have been studied in nine variant lines of the Shionogi carcinoma, two of which are androgen dependent and seven of which are autonomous. The dependent lines, and two of the seven autonomous lines, contain androgen receptors; this finding demonstrates that the presence of receptors is not an accurate marker of hormonal dependence in vivo. Since the ability to transport androgens into the nucleus, as judged from the relative maximal rates of transport, is virtually restricted to dependent and autonomous lines which possess cytoplasmic receptors, it is clear that such receptors may play a role in regulating the intranuclear concentration of androgens. The absence of cytoplasmic receptors and the comparative lack of perceptible transfer of androgens across the nuclear membrane are features peculiar to the autonomous condition."} {"id": "PMID:163101", "title": "Altered hormone control of cyclic AMP formation in isolated parenchymal liver cells from rats treated with 2-acetylaminofluorene.", "content": "The hormone control of cyclic AMP-formation in isolated parenchymal liver cells from rats fed the carcinogen 2-acetylaminofluorene (0.025% for 4-8 weeks) was studied. The cells from the carcinogen-treated animals responded much more strongly to adrenergic agents than cells from control animals, while no significant difference was found for the glucagon effect. Of the adrenergic substances studied, the order of potency was isoprenalin larger than or equal to adrenalin larger than phhenylephrine; stimulation was blocked by propranolol, but not by phentolamine. The effects of supramaximal concentrations of isoprenalin and glucagon were not additive.", "contents": "Altered hormone control of cyclic AMP formation in isolated parenchymal liver cells from rats treated with 2-acetylaminofluorene. The hormone control of cyclic AMP-formation in isolated parenchymal liver cells from rats fed the carcinogen 2-acetylaminofluorene (0.025% for 4-8 weeks) was studied. The cells from the carcinogen-treated animals responded much more strongly to adrenergic agents than cells from control animals, while no significant difference was found for the glucagon effect. Of the adrenergic substances studied, the order of potency was isoprenalin larger than or equal to adrenalin larger than phhenylephrine; stimulation was blocked by propranolol, but not by phentolamine. The effects of supramaximal concentrations of isoprenalin and glucagon were not additive."} {"id": "PMID:163102", "title": "Stimulation of cyclic adenosine 3':5'-monophosphate and corticosterone formation in isolated rat adrenal cells by cholera enterotoxin. Comparison with the effects of ACTH.", "content": "1. The production of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and corticosterone isolated ratadrenal cells was increased by cholera enterotoxin. Both responses were accompanied by a lag period which is characteristic of other known actions of enterotoxin. The duration of the lag period in the production of corticosterone depended on the concentration of enterotoxin; with the maximally stimulating amounts it was 30-45 min. 2. Maximum rates of cyclic AMP and corticosterone synthesis, after the lag period, were constant for at least 1 h. Although the maximum rate of corticosterone formation was the same as that obtained adrenocorticotropic hormone, the maximum rate of cyclic AMP formation was only 8-10% of that with adrenocorticotropic hormone. 3. Pretreatment of the cells with enterotoxin ahd no effect on their subsequent steroidogenic response to maximally stimulating amounts of adrenocorticotropic hormone. 4. Cycloheximide inhibited the effect of both enterotoxin and adrenocorticotropic hormone on corticosterone production. 5. Enterotoxin stimulation of both cyclic AMP and corticosterone formation was dependent on the presence of Ca2+ in the medium although the Ca2+ requirement was not same as that for adrenocorticotropic hormone. Thus, EGTA at concentrations which completely abolished the effect of adrenocorticotropic hormone caused only a partial reduction in the effects of enterotoxin. 6. Exogenously added choleragenoid and gangliosides abolished the effects of enterotoxin without having any significant effect on the response of the cells to adrenocorticotropic hormone. 7. After treatment with neuraminidase, the adrenal cells showed an increased response to enterotoxin in terms of both cyclic AMP and corticosterone formation which was due to a combination of two effects: (a) increased rate of synthesis of both compounds and (b) shortening of the characteristic lag period. This is in sharp contrast to the results obtained with adrenocorticotropic hormone where neuraminidase-treatment made the cells less sensitive to adrenocorticotropic hormone.", "contents": "Stimulation of cyclic adenosine 3':5'-monophosphate and corticosterone formation in isolated rat adrenal cells by cholera enterotoxin. Comparison with the effects of ACTH. 1. The production of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and corticosterone isolated ratadrenal cells was increased by cholera enterotoxin. Both responses were accompanied by a lag period which is characteristic of other known actions of enterotoxin. The duration of the lag period in the production of corticosterone depended on the concentration of enterotoxin; with the maximally stimulating amounts it was 30-45 min. 2. Maximum rates of cyclic AMP and corticosterone synthesis, after the lag period, were constant for at least 1 h. Although the maximum rate of corticosterone formation was the same as that obtained adrenocorticotropic hormone, the maximum rate of cyclic AMP formation was only 8-10% of that with adrenocorticotropic hormone. 3. Pretreatment of the cells with enterotoxin ahd no effect on their subsequent steroidogenic response to maximally stimulating amounts of adrenocorticotropic hormone. 4. Cycloheximide inhibited the effect of both enterotoxin and adrenocorticotropic hormone on corticosterone production. 5. Enterotoxin stimulation of both cyclic AMP and corticosterone formation was dependent on the presence of Ca2+ in the medium although the Ca2+ requirement was not same as that for adrenocorticotropic hormone. Thus, EGTA at concentrations which completely abolished the effect of adrenocorticotropic hormone caused only a partial reduction in the effects of enterotoxin. 6. Exogenously added choleragenoid and gangliosides abolished the effects of enterotoxin without having any significant effect on the response of the cells to adrenocorticotropic hormone. 7. After treatment with neuraminidase, the adrenal cells showed an increased response to enterotoxin in terms of both cyclic AMP and corticosterone formation which was due to a combination of two effects: (a) increased rate of synthesis of both compounds and (b) shortening of the characteristic lag period. This is in sharp contrast to the results obtained with adrenocorticotropic hormone where neuraminidase-treatment made the cells less sensitive to adrenocorticotropic hormone."} {"id": "PMID:163103", "title": "[3H] norepinephrine binding by rat glial cells in culture. Lack of correlation between binding and adenylate cyclase activation.", "content": "Subcellular fractions prepared from rat glial cells in culture (clonal line c6) were used in an attempt to characterize the adrenergic receptor involved in adenylate cyclase activation. Both [3H] norepinephrine binding and enzyme activation were measured under identical experimental conditions. Binding sites for norepinephrine could be detected; their main characteristics were: apparant Km: 4 - 10-6 M, macimal capacity: 20 pmol/mg protein. Their stereospecificity towards structually related drugs was found to be different from the stereospecificity of the receptor involved in adenylate cyclase activation. Thus, 3-methoxydopamine (a competitive inhibitor of norepinephrine for adenylate cyclase activation), phenylephrine (a partial adrennergic agonist) and the blocking agent propranolol were unable to compete with [3H] norepinephrine for binding. On the other hand, several molecules like dopa bearing a catechol group and which are unable to interact with the adenylate cyclase as agonists or competitive inhibitors strongly inhibited [3H] norepinephrine binding. As in several other systems so far studied, the presence on the glial cell's membrane of a large number of \"catechol-binding sites\" makes it difficult to characterize the beta-adrenergic receptor.", "contents": "[3H] norepinephrine binding by rat glial cells in culture. Lack of correlation between binding and adenylate cyclase activation. Subcellular fractions prepared from rat glial cells in culture (clonal line c6) were used in an attempt to characterize the adrenergic receptor involved in adenylate cyclase activation. Both [3H] norepinephrine binding and enzyme activation were measured under identical experimental conditions. Binding sites for norepinephrine could be detected; their main characteristics were: apparant Km: 4 - 10-6 M, macimal capacity: 20 pmol/mg protein. Their stereospecificity towards structually related drugs was found to be different from the stereospecificity of the receptor involved in adenylate cyclase activation. Thus, 3-methoxydopamine (a competitive inhibitor of norepinephrine for adenylate cyclase activation), phenylephrine (a partial adrennergic agonist) and the blocking agent propranolol were unable to compete with [3H] norepinephrine for binding. On the other hand, several molecules like dopa bearing a catechol group and which are unable to interact with the adenylate cyclase as agonists or competitive inhibitors strongly inhibited [3H] norepinephrine binding. As in several other systems so far studied, the presence on the glial cell's membrane of a large number of \"catechol-binding sites\" makes it difficult to characterize the beta-adrenergic receptor."} {"id": "PMID:163104", "title": "Transformation of the rat uterine estrogen receptor after partial purification.", "content": "Warming crude ratuterine cytosol after the addition of [3H] estradiol accelerates the association of the 4-S estrogen-binding protein with a second macromolecule, resulting in the formation of the 5-S estrogen-binding protein. To determine whether the 5-S estrogen-binding protein consists of two similar or dissimilar subunits, uterine cytosol was subjected to a number of fractionation procedures that separate macromolecules by solubility, molecular gel sieving, sedimentation rate, ionic charge, and heat lability. Following each of these methods, the fraction containing the 4-S estrogen-binding protein was incubated at 28 degrees C; each of the these 4-S estrogen-binding protein-containing fractions retained its capacity to completely transform to the 5-S estrogen-binding protein. In samples subjected to partial purification procedures, it was necessary that the buffer contain 40 mM Tris, 60 mM Tris, 60 mM KC1, 1-10 MM dithiothreitol, and 1 M urea at pH 7.4, in order to accomplish the 4-S to 5-S estrogen-binding protein transformation at 25 degrees C. Formation of the 5-S estrogen-binding protein requires association of the 4-Estrogen-binding protein with a molecule identical to or very similar to itself.", "contents": "Transformation of the rat uterine estrogen receptor after partial purification. Warming crude ratuterine cytosol after the addition of [3H] estradiol accelerates the association of the 4-S estrogen-binding protein with a second macromolecule, resulting in the formation of the 5-S estrogen-binding protein. To determine whether the 5-S estrogen-binding protein consists of two similar or dissimilar subunits, uterine cytosol was subjected to a number of fractionation procedures that separate macromolecules by solubility, molecular gel sieving, sedimentation rate, ionic charge, and heat lability. Following each of these methods, the fraction containing the 4-S estrogen-binding protein was incubated at 28 degrees C; each of the these 4-S estrogen-binding protein-containing fractions retained its capacity to completely transform to the 5-S estrogen-binding protein. In samples subjected to partial purification procedures, it was necessary that the buffer contain 40 mM Tris, 60 mM Tris, 60 mM KC1, 1-10 MM dithiothreitol, and 1 M urea at pH 7.4, in order to accomplish the 4-S to 5-S estrogen-binding protein transformation at 25 degrees C. Formation of the 5-S estrogen-binding protein requires association of the 4-Estrogen-binding protein with a molecule identical to or very similar to itself."} {"id": "PMID:163105", "title": "Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum. Mediation by adenosine 3':5'-monophosphate.", "content": "The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of alpha-amino [1-14C] isobutyrate or [1-14C] cycloleucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate amino-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r=0.977). Theophylline and prostaglandin E1, WHICH RAISE CARTILAGE CYCLIC AMP also increase amino-aminoisobutyrate transport. Exogenous cyclic AMP, N6-monobutyryl cyclic AMP and n6, 02'-dibutyryl cyclic AMP increase cartilage amino-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP.", "contents": "Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum. Mediation by adenosine 3':5'-monophosphate. The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of alpha-amino [1-14C] isobutyrate or [1-14C] cycloleucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate amino-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r=0.977). Theophylline and prostaglandin E1, WHICH RAISE CARTILAGE CYCLIC AMP also increase amino-aminoisobutyrate transport. Exogenous cyclic AMP, N6-monobutyryl cyclic AMP and n6, 02'-dibutyryl cyclic AMP increase cartilage amino-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP."} {"id": "PMID:163107", "title": "[The potential nuclease activity of the T antigen of SV-40 virus].", "content": "SV40 T-antigens were isolated from an extract of golden hamster tumours by precipitation with ammonium sulphate with subsequent fractionation on DEAE cellulose. The degree of purification of the preparation proved to be about 100-fold; it, however, contained an admixture of several cell proteins. Treatment of the DNA of the calf thymus with the T-antigen preparation in the presence of magnesium ions decreased the viscosity of the DNA solution during the first hour of incubation. T-antigen inactivated by heating, and also a fraction of normal hamster tissues analogous to it produced no such effect. In case of centrifugation in the saccharose gradient the constant of DNA sedimentation fell after the treatment with T-antigen from 285 to 165, this corresponding to about4--5-fold reduction of molecular weight of the DNA. The data obtained indicated that the partially purified T-antigen preparation possessed endonuclease activity.", "contents": "[The potential nuclease activity of the T antigen of SV-40 virus]. SV40 T-antigens were isolated from an extract of golden hamster tumours by precipitation with ammonium sulphate with subsequent fractionation on DEAE cellulose. The degree of purification of the preparation proved to be about 100-fold; it, however, contained an admixture of several cell proteins. Treatment of the DNA of the calf thymus with the T-antigen preparation in the presence of magnesium ions decreased the viscosity of the DNA solution during the first hour of incubation. T-antigen inactivated by heating, and also a fraction of normal hamster tissues analogous to it produced no such effect. In case of centrifugation in the saccharose gradient the constant of DNA sedimentation fell after the treatment with T-antigen from 285 to 165, this corresponding to about4--5-fold reduction of molecular weight of the DNA. The data obtained indicated that the partially purified T-antigen preparation possessed endonuclease activity."} {"id": "PMID:163108", "title": "Long survival after operation for cancer of the lung.", "content": "A survey is presented of 293 cases of lung cancer operated on by one surgeon over a period of 35 years. Lobectomy was done in 86 cases with a mortality of 3.5 per cent. Simple pneumonectomy was done in 89 cases with a mortality of 20 per cent, and radical pneumonectomy in 118 cases with a mortality of 15-25 per cent. The survival rate after 5 or more years for lobectomy was 41 per cent (34 patients). After simple pneumonectomy 21 patients (30 per cent) lived 5 years or more, and after radical pneumonectomy 39 patients (39 per cent) lived 5 years or more. The survival of the patients in whom the excised lymph nodes were involved by growth is presented. It is pointed out that at least 1 in 3 patients with cancer of the lung treated by operation was alive 5 years later. The very good long term results are presented including the 10-year and 20-year survival rate. Two patients are still alive after 30 and 34 years respectively. One patient is alive 29 years after a lobectomy and 13 years after a contralateral lobectomy for a new primary cancer. A second new cancer occurred in 9 patients. Continuance of smoking is shown to be harmful. The factors affecting the long term freedom from recurrence are discussed. The cell type of the cancer is shown to be important. Squamous-celled growths have the best results and oat-celled and small-celled the worst, although long term survival can follow operation for both these. The occurrence of a pleural infection after operation may be favourable to long term freedom from recurrence and this way probably so in 2 patients who lived 25 and 27 years respectively and 1 patient who is still alive after 34 years. On the whole the evidence is unconvincing that much benefit may follow radiotherapy combined with operation.", "contents": "Long survival after operation for cancer of the lung. A survey is presented of 293 cases of lung cancer operated on by one surgeon over a period of 35 years. Lobectomy was done in 86 cases with a mortality of 3.5 per cent. Simple pneumonectomy was done in 89 cases with a mortality of 20 per cent, and radical pneumonectomy in 118 cases with a mortality of 15-25 per cent. The survival rate after 5 or more years for lobectomy was 41 per cent (34 patients). After simple pneumonectomy 21 patients (30 per cent) lived 5 years or more, and after radical pneumonectomy 39 patients (39 per cent) lived 5 years or more. The survival of the patients in whom the excised lymph nodes were involved by growth is presented. It is pointed out that at least 1 in 3 patients with cancer of the lung treated by operation was alive 5 years later. The very good long term results are presented including the 10-year and 20-year survival rate. Two patients are still alive after 30 and 34 years respectively. One patient is alive 29 years after a lobectomy and 13 years after a contralateral lobectomy for a new primary cancer. A second new cancer occurred in 9 patients. Continuance of smoking is shown to be harmful. The factors affecting the long term freedom from recurrence are discussed. The cell type of the cancer is shown to be important. Squamous-celled growths have the best results and oat-celled and small-celled the worst, although long term survival can follow operation for both these. The occurrence of a pleural infection after operation may be favourable to long term freedom from recurrence and this way probably so in 2 patients who lived 25 and 27 years respectively and 1 patient who is still alive after 34 years. On the whole the evidence is unconvincing that much benefit may follow radiotherapy combined with operation."} {"id": "PMID:163106", "title": "[Temperature dependence of the epr spectra of a spin-labeled myosin and its complex with adp].", "content": "The effect of temperature on ESR spectra of spin-labelled myosin and myosin-ADP complex was studied. It was shown that mobility of the sptrongly immobilized spin label almost did not change with temperature (-2 degrees C-37 degrees C) whereas mobility of the slightly immobilized spin label changed in a complicated manner and not monotonously. The observed changes in mobility of the slightly immobilized spin label and characteristics of the ESP spectrum of the myosin-ADP complex suggest that temperature causes continuous changes of the structure in the local environment of the binding sites of the spin label, and on the average, one conformation of myosin and myosin-ADP complex molecules exists at any temperature.", "contents": "[Temperature dependence of the epr spectra of a spin-labeled myosin and its complex with adp]. The effect of temperature on ESR spectra of spin-labelled myosin and myosin-ADP complex was studied. It was shown that mobility of the sptrongly immobilized spin label almost did not change with temperature (-2 degrees C-37 degrees C) whereas mobility of the slightly immobilized spin label changed in a complicated manner and not monotonously. The observed changes in mobility of the slightly immobilized spin label and characteristics of the ESP spectrum of the myosin-ADP complex suggest that temperature causes continuous changes of the structure in the local environment of the binding sites of the spin label, and on the average, one conformation of myosin and myosin-ADP complex molecules exists at any temperature."} {"id": "PMID:163111", "title": "Oestrogen receptors in breast cancer: a changing concept.", "content": "Oestrogen receptors were found in 156 (73%) out of 214 primary breast cancers and in 98 (58%) out of 168 metastatic deposits. These proportions reached 82% and 70% respectively in the second half of the study. Receptors were not found in samples of normal breast tissue but small amounts were present in tissue from some hyperplastic lesions and in male gynaecomastia. Receptor concentrations in the malignant samples were evenly distributed over a wide range of values, suggesting that even \"negative\" tumours might contain trace amounts undetectable by the method used. Each tumour was characterized by a given level of receptor concentration. In most cases the amounts found in the invaded axillary nodes and their corresponding primary tumours were the same. We suggest that quantitative rather than qualitative assessment should provide an appropriate criterion for studies of biochemical and clinical correlations.", "contents": "Oestrogen receptors in breast cancer: a changing concept. Oestrogen receptors were found in 156 (73%) out of 214 primary breast cancers and in 98 (58%) out of 168 metastatic deposits. These proportions reached 82% and 70% respectively in the second half of the study. Receptors were not found in samples of normal breast tissue but small amounts were present in tissue from some hyperplastic lesions and in male gynaecomastia. Receptor concentrations in the malignant samples were evenly distributed over a wide range of values, suggesting that even \"negative\" tumours might contain trace amounts undetectable by the method used. Each tumour was characterized by a given level of receptor concentration. In most cases the amounts found in the invaded axillary nodes and their corresponding primary tumours were the same. We suggest that quantitative rather than qualitative assessment should provide an appropriate criterion for studies of biochemical and clinical correlations."} {"id": "PMID:163114", "title": "Role of respiratory viruses in childhood mortality.", "content": "Respiratory viruses have been identified at necropsy in the lungs of 13 out of 24 children who died with observed acute respiratory illness. The histological appearances of the lungs supported the association between virus and death in each of these 13 children and suggested an unidentified virus aetiology in a further five cases. Histological appearances compatible with bacterial infection were found in the lungs of only two of the 24 children. Similar virus and histological findings have been reported in about one-third of victims of the sudden infant death syndrome (cot deaths), indicating a rapid unobserved respiratory virus infection as the most likely mode of death in this group. Evidence that respiratory viruses may be involved in a larger proportion of sudden unexpected deaths, perhaps as antigens in a hypersensitivity reaction, is discussed. Respiratory viruses seem the major identifiable agents contributing to the maintenance of the postneonatal mortality rate since acute respiratory illness and the sudden infant death syndrome together account for about two-thirds of deaths at this age.", "contents": "Role of respiratory viruses in childhood mortality. Respiratory viruses have been identified at necropsy in the lungs of 13 out of 24 children who died with observed acute respiratory illness. The histological appearances of the lungs supported the association between virus and death in each of these 13 children and suggested an unidentified virus aetiology in a further five cases. Histological appearances compatible with bacterial infection were found in the lungs of only two of the 24 children. Similar virus and histological findings have been reported in about one-third of victims of the sudden infant death syndrome (cot deaths), indicating a rapid unobserved respiratory virus infection as the most likely mode of death in this group. Evidence that respiratory viruses may be involved in a larger proportion of sudden unexpected deaths, perhaps as antigens in a hypersensitivity reaction, is discussed. Respiratory viruses seem the major identifiable agents contributing to the maintenance of the postneonatal mortality rate since acute respiratory illness and the sudden infant death syndrome together account for about two-thirds of deaths at this age."} {"id": "PMID:163116", "title": "Cerebellar responses to teleceptive stimuli in alert monkeys.", "content": "Discharges of single Purkinje cells in the intermediate and lateral zones of the cerebellar cortex and of neurons in the interpositus and dentate nuclei were recorded in alert monkeys during the presentation of intense auditory and visual stimuli. Concomitant monitoring of the electromyogram (EMG) demonstrated that these stimuli evoked characteristic startle responses in most instances. Firing patterns of cerebellar nuclear cells to auditory stimuli could be categorized into four types, the most common of which consisted of a short-latency acceleration of discharge, followed by a decrease in activity, and in most cells by a later period of facilitation. Simple spike discharge patterns of Purkinje cells consisted largely of prolonged increases or decreases in firing rate, although more complex patterns were seen. In almost 50% of the Purkinje cells tested, complex spikes were evoked by the auditory stimuli. Comparison of simple spike responses of Purkinje cells and of the discharges of cerebellar nuclear cells to auditory and visual inputs revealed that, except for a longer latency, the discharge pattern evoked by flash stimuli was identical to that evoked by sound in all instances. By contrast, in about one-third of the Purkinje cells with related complex spike discharge, complex spikes were evoked by stimuli of only a single modality. Comparison of the times of changes in nuclear and Purkinje cell activity suggests that the initial change in nuclear cell discharge was due to an increase in mossy fiber activity, while the subsequent decrease resulted from Purkinje cell inhibition evoked by mossy and climbing fiber inputs. The absence of increases in nuclear cell discharge at the time of most decreases in Purkinje activity indicates that removal of Purkinje inhibition does not have a major effect on the discharge rates of individual nuclear cells. The data also suggest that excitation of nuclear cells via climbing fiber collaterals played only a minor role in influencing their discharge. Since most EMG changes occurred after or at about the same time as the initial changes in cerebellar discharge, it is unlikely that the initial changes in cerebellar activity were a result of feedback from contracting muscles. It is proposed that the similar discharge patterns of cerebellar neurons to auditory and visual input results from a convergence of these inputs on a structure which projects to the cerebellum as mossy fibers.", "contents": "Cerebellar responses to teleceptive stimuli in alert monkeys. Discharges of single Purkinje cells in the intermediate and lateral zones of the cerebellar cortex and of neurons in the interpositus and dentate nuclei were recorded in alert monkeys during the presentation of intense auditory and visual stimuli. Concomitant monitoring of the electromyogram (EMG) demonstrated that these stimuli evoked characteristic startle responses in most instances. Firing patterns of cerebellar nuclear cells to auditory stimuli could be categorized into four types, the most common of which consisted of a short-latency acceleration of discharge, followed by a decrease in activity, and in most cells by a later period of facilitation. Simple spike discharge patterns of Purkinje cells consisted largely of prolonged increases or decreases in firing rate, although more complex patterns were seen. In almost 50% of the Purkinje cells tested, complex spikes were evoked by the auditory stimuli. Comparison of simple spike responses of Purkinje cells and of the discharges of cerebellar nuclear cells to auditory and visual inputs revealed that, except for a longer latency, the discharge pattern evoked by flash stimuli was identical to that evoked by sound in all instances. By contrast, in about one-third of the Purkinje cells with related complex spike discharge, complex spikes were evoked by stimuli of only a single modality. Comparison of the times of changes in nuclear and Purkinje cell activity suggests that the initial change in nuclear cell discharge was due to an increase in mossy fiber activity, while the subsequent decrease resulted from Purkinje cell inhibition evoked by mossy and climbing fiber inputs. The absence of increases in nuclear cell discharge at the time of most decreases in Purkinje activity indicates that removal of Purkinje inhibition does not have a major effect on the discharge rates of individual nuclear cells. The data also suggest that excitation of nuclear cells via climbing fiber collaterals played only a minor role in influencing their discharge. Since most EMG changes occurred after or at about the same time as the initial changes in cerebellar discharge, it is unlikely that the initial changes in cerebellar activity were a result of feedback from contracting muscles. It is proposed that the similar discharge patterns of cerebellar neurons to auditory and visual input results from a convergence of these inputs on a structure which projects to the cerebellum as mossy fibers."} {"id": "PMID:163117", "title": "Quantitative aspects of the shift-effect in cat retinal ganglion cells.", "content": "A sudden displacement of a pattern, even when far away from the classical border of a concentrically organized receptive field, elicits a transient excitatory response in on- and off-center retinal ganglion cells (shift-effect). Peak response and latency of the shift-effect have been studied under various stimulus conditions in on- and off-center ganglion cells. Increasing the retinal distance between the site of stimulation and receptive field yields responses of increasing latency corresponding to an intraretinal conduction velocity of about 0.35 m/sec. Beyond a distance of 20 degrees response amplitudes decrease steadily in on- and off-center neurons. Shift amplitude and contrast of the shifting grating have almost no influence above a threshold of 30 min of arc and 10-20% modulation respectively (all-or-none behavior). Shifts of decreasing velocity (600-10 degrees/sec) increase the latency. The response magnitude decreases only at very slow movements. Other properties of the shift-effect are briefly reported. Possible functional significances in relation to eye movements and brightness perception and the retinal pathway of the shift-effect are discussed.", "contents": "Quantitative aspects of the shift-effect in cat retinal ganglion cells. A sudden displacement of a pattern, even when far away from the classical border of a concentrically organized receptive field, elicits a transient excitatory response in on- and off-center retinal ganglion cells (shift-effect). Peak response and latency of the shift-effect have been studied under various stimulus conditions in on- and off-center ganglion cells. Increasing the retinal distance between the site of stimulation and receptive field yields responses of increasing latency corresponding to an intraretinal conduction velocity of about 0.35 m/sec. Beyond a distance of 20 degrees response amplitudes decrease steadily in on- and off-center neurons. Shift amplitude and contrast of the shifting grating have almost no influence above a threshold of 30 min of arc and 10-20% modulation respectively (all-or-none behavior). Shifts of decreasing velocity (600-10 degrees/sec) increase the latency. The response magnitude decreases only at very slow movements. Other properties of the shift-effect are briefly reported. Possible functional significances in relation to eye movements and brightness perception and the retinal pathway of the shift-effect are discussed."} {"id": "PMID:163121", "title": "Generation of spike trains in CNS neurons.", "content": "The membrane potential waveforms to be expected from many asynchronous inputs to CNS neurons are described, along with modes for repetitive firing through which the input waveforms are converted into spike trains. Area beneath a postsynaptic potential (PSP), rather than PSP peak height, is shown to be an important parameter susceptible to modification. Occasional crossings of threshold produce occasional spikes, but a sustained depolarizing waveform which attempts to hold the membrane potential above threshold elicits rhythmic firing. Firing rate is graded with the amount by which the synaptic depolarizing currents exceed the minimum current for rhythmic firing (approximately rheobase). A systematic sequence of alterations in the membrane potential trajectory between spikes, quite different from those of receptors and invertebrate neurons, may control the firing rate and give rise to sudden changes in the \"gain\" of this conversion of depolarizing current into firing rate. The different implications of synaptic location during the occasional spike mode and the rhythmic firing mode are discussed, as is the role of the antidromic invasion of the soma-dendritic region during rhythmic firing. Less frequently an\"extra spike mode\" is seen where depolarizing afterpotentials following a spike themselves cross threshold to elicit an extra spike, which may similarly elicit another extra spike, etc., in a regenerative cycle. The character of the underlying depolarizing afterpotentials (or \"delayed depolarizations\") is reviewed, along with theories for their origin from the antidromic invasion of the dendritic tree. The stereotyped burst firing patterns characteristic of the extra spike mode can also be seen in deafferented neurons and neurons studied in chronic syndromes such as epilepsy and central pain. This raises the question as to whether some disease states may augment extra spike firing, thus multiplying many-fold the response to a normal input.", "contents": "Generation of spike trains in CNS neurons. The membrane potential waveforms to be expected from many asynchronous inputs to CNS neurons are described, along with modes for repetitive firing through which the input waveforms are converted into spike trains. Area beneath a postsynaptic potential (PSP), rather than PSP peak height, is shown to be an important parameter susceptible to modification. Occasional crossings of threshold produce occasional spikes, but a sustained depolarizing waveform which attempts to hold the membrane potential above threshold elicits rhythmic firing. Firing rate is graded with the amount by which the synaptic depolarizing currents exceed the minimum current for rhythmic firing (approximately rheobase). A systematic sequence of alterations in the membrane potential trajectory between spikes, quite different from those of receptors and invertebrate neurons, may control the firing rate and give rise to sudden changes in the \"gain\" of this conversion of depolarizing current into firing rate. The different implications of synaptic location during the occasional spike mode and the rhythmic firing mode are discussed, as is the role of the antidromic invasion of the soma-dendritic region during rhythmic firing. Less frequently an\"extra spike mode\" is seen where depolarizing afterpotentials following a spike themselves cross threshold to elicit an extra spike, which may similarly elicit another extra spike, etc., in a regenerative cycle. The character of the underlying depolarizing afterpotentials (or \"delayed depolarizations\") is reviewed, along with theories for their origin from the antidromic invasion of the dendritic tree. The stereotyped burst firing patterns characteristic of the extra spike mode can also be seen in deafferented neurons and neurons studied in chronic syndromes such as epilepsy and central pain. This raises the question as to whether some disease states may augment extra spike firing, thus multiplying many-fold the response to a normal input."} {"id": "PMID:163122", "title": "Modulation of cortical and pyramidal tract induced motor responses by electrical stimulation of the basal ganglia.", "content": "Two general mechanisms based on anatomical studies are possible for modulation of motor activity by the caudate nucleus and globus pallidus. These mechanisms are: (1) modulation of the output of cortical neurons that exert motor influences; and (2) modulation of subcortical neurons that exert motor influences. Differentiation between these two mechanisms was accomplished in the present study by two experimental approaches, both of which employed the conditioning-test paradigm. The first approach was an investigation of caudate nucleus or globus pallidus modulation (conditioning stimulus) of flexor responses of the anterior tibialis muscle elicited by electrical stimulation of the sensorimotor cortex (test stimulus) or pyramidal tract (test stimulus). These investigations were carried out in the intact and in decorticate cats. The second approach was an analysis of modulation or cortically induced pyramidal tract responses (direct and indirect, D-I potentials) by conditioning shock trains delivered to various loci within the caudate nucleus or globus pallidus. Both approaches were designed to determine whixh inhibitory and facilitatory motor influences of the basal ganglia occurred at a cortical or subcortical level. Simultaneous stimulation of a locus within the caudate nucleus and the sensorimotor cortex evoked either an enhancement, reduction or no alteration of the cortically induced increase in flexor responses (measured by Ia afferent activity, EMG, myogram). In contrast, no inhibitory influences occurred from caudate nucleus stimulation upon pyramidal tract induced flexor responses in either the intact or decorticate preparation. Inhibitory loci were distributed toward the rostral portion of the caudate nucleus, whereas facilitatory loci were distributed throughout; this distribution was statistically significant (chi2; P less than 0.01). Only enhancement or no influence upon cortical induced or pyramidal tract induced responses were obtained by conditioning stimuli to the globus pallidus. In the unanesthetized but immobilized cat, trains of shocks delivered to the caudate nucleus enhanced, reduced or had no influence upon the cortically evoked direct (D) and indirect (I) potentials recorded in the bulbar pyramidal tract. The distribution of facilitatory and inhibitory loci was organized in a similar fashion as in theanesthetized preparation. From these observations, a model was proposed in which the output of the caudate nucleus exerts both facilitatory or inhibitory modulation of the tonically active globus pallidus cells. The latter in turn predominantly or exclusively facilitate output of pyramidal tract neurons as well as the output of subcortical structures; both effects facilitate motor responses at the spinal level.", "contents": "Modulation of cortical and pyramidal tract induced motor responses by electrical stimulation of the basal ganglia. Two general mechanisms based on anatomical studies are possible for modulation of motor activity by the caudate nucleus and globus pallidus. These mechanisms are: (1) modulation of the output of cortical neurons that exert motor influences; and (2) modulation of subcortical neurons that exert motor influences. Differentiation between these two mechanisms was accomplished in the present study by two experimental approaches, both of which employed the conditioning-test paradigm. The first approach was an investigation of caudate nucleus or globus pallidus modulation (conditioning stimulus) of flexor responses of the anterior tibialis muscle elicited by electrical stimulation of the sensorimotor cortex (test stimulus) or pyramidal tract (test stimulus). These investigations were carried out in the intact and in decorticate cats. The second approach was an analysis of modulation or cortically induced pyramidal tract responses (direct and indirect, D-I potentials) by conditioning shock trains delivered to various loci within the caudate nucleus or globus pallidus. Both approaches were designed to determine whixh inhibitory and facilitatory motor influences of the basal ganglia occurred at a cortical or subcortical level. Simultaneous stimulation of a locus within the caudate nucleus and the sensorimotor cortex evoked either an enhancement, reduction or no alteration of the cortically induced increase in flexor responses (measured by Ia afferent activity, EMG, myogram). In contrast, no inhibitory influences occurred from caudate nucleus stimulation upon pyramidal tract induced flexor responses in either the intact or decorticate preparation. Inhibitory loci were distributed toward the rostral portion of the caudate nucleus, whereas facilitatory loci were distributed throughout; this distribution was statistically significant (chi2; P less than 0.01). Only enhancement or no influence upon cortical induced or pyramidal tract induced responses were obtained by conditioning stimuli to the globus pallidus. In the unanesthetized but immobilized cat, trains of shocks delivered to the caudate nucleus enhanced, reduced or had no influence upon the cortically evoked direct (D) and indirect (I) potentials recorded in the bulbar pyramidal tract. The distribution of facilitatory and inhibitory loci was organized in a similar fashion as in theanesthetized preparation. From these observations, a model was proposed in which the output of the caudate nucleus exerts both facilitatory or inhibitory modulation of the tonically active globus pallidus cells. The latter in turn predominantly or exclusively facilitate output of pyramidal tract neurons as well as the output of subcortical structures; both effects facilitate motor responses at the spinal level."} {"id": "PMID:163125", "title": "The use of frozen cells in the microtitre serum neutralization test for infectious bovine rhinotracheitis.", "content": "Some parameters of the microtitre serum neutralization test were examined when using bovine fetal kidney cells derived from stocks stored in liquid nitrogen. In replicate tests with one serum there was no significant difference (p greater than 0.05) between titres calculated on the basis of cytopathic effect when either two or four wells were used per serum dilution. Also, there was no significant difference between titres calculated on the basis of a cell staining method when either two or four wells were used per serum dilution. When titres obtained by the 2-well-cytopathic effect method were compared with those obtained by the 2-well-stain method differences were not significantly different and it was concluded that the latter method using frozen cells constituted a practical and reproducible test. No significant titre variation occurred in cells serially passaged after having been frozen, or in cells derived from five different fetuses. Titres of sera from 41 cattle conformed to a log normal distribution pattern.", "contents": "The use of frozen cells in the microtitre serum neutralization test for infectious bovine rhinotracheitis. Some parameters of the microtitre serum neutralization test were examined when using bovine fetal kidney cells derived from stocks stored in liquid nitrogen. In replicate tests with one serum there was no significant difference (p greater than 0.05) between titres calculated on the basis of cytopathic effect when either two or four wells were used per serum dilution. Also, there was no significant difference between titres calculated on the basis of a cell staining method when either two or four wells were used per serum dilution. When titres obtained by the 2-well-cytopathic effect method were compared with those obtained by the 2-well-stain method differences were not significantly different and it was concluded that the latter method using frozen cells constituted a practical and reproducible test. No significant titre variation occurred in cells serially passaged after having been frozen, or in cells derived from five different fetuses. Titres of sera from 41 cattle conformed to a log normal distribution pattern."} {"id": "PMID:163126", "title": "Infectious bovine keratoconjunctivitis I. Experimental production.", "content": "One or both eyes of 20 calves were inoculated one or more time with variou(s combinations of microorganism (live oor killed Moraxella bovis, infectious bovine rhinotracheitis virus, bovine adenovirus, bovine parainfluenza-3 virus and Mycoplasma bovoculi) by conjunctival instillation or direct inoculation of the conjunctivea or cornea. The eyes of all the calves received natural or artificial ultraviolet irradiation. Neither the adenovirus nor parainfluenza-3 virus became established in the eye or produced keratoconjunctivitis. Both M. bovis and infectious bovine rhinotracheitis virus became established in the bovine eye and produced disease. Subconjunctival or intracorneal inoculation of M. bovis caused a severe disease, simulating natural infectious bovine keratoconjunctivitis. Only the intracorneal inoculation of mycoplasma produced severe keratoconjunctivits. Eyes that on initial exposure to M. bovis became severly inflamed were more resistant to a second or third exposure to M. bovis, presumably by enhanced local defence mechanisms.", "contents": "Infectious bovine keratoconjunctivitis I. Experimental production. One or both eyes of 20 calves were inoculated one or more time with variou(s combinations of microorganism (live oor killed Moraxella bovis, infectious bovine rhinotracheitis virus, bovine adenovirus, bovine parainfluenza-3 virus and Mycoplasma bovoculi) by conjunctival instillation or direct inoculation of the conjunctivea or cornea. The eyes of all the calves received natural or artificial ultraviolet irradiation. Neither the adenovirus nor parainfluenza-3 virus became established in the eye or produced keratoconjunctivitis. Both M. bovis and infectious bovine rhinotracheitis virus became established in the bovine eye and produced disease. Subconjunctival or intracorneal inoculation of M. bovis caused a severe disease, simulating natural infectious bovine keratoconjunctivitis. Only the intracorneal inoculation of mycoplasma produced severe keratoconjunctivits. Eyes that on initial exposure to M. bovis became severly inflamed were more resistant to a second or third exposure to M. bovis, presumably by enhanced local defence mechanisms."} {"id": "PMID:163127", "title": "Further observations on the characteristics of a bovine parainfluenza-3 variant.", "content": "Calves were inoculated with a bovine para-influenza-3 variant to determine its pathogenicity and the stability of its cytopathic feature and its inability to agglutinate chicken erythrocytes. The inoculated calves and one contact animal developed an immune response without significant clinical illness. The clinical response in calves was similar to that induced by the parent virus strain. The variant was shown to retain its characteristic cytopathic effect for Madin Darby bovine kidney cells and its property of hemagglutination following one passage in the natural host.", "contents": "Further observations on the characteristics of a bovine parainfluenza-3 variant. Calves were inoculated with a bovine para-influenza-3 variant to determine its pathogenicity and the stability of its cytopathic feature and its inability to agglutinate chicken erythrocytes. The inoculated calves and one contact animal developed an immune response without significant clinical illness. The clinical response in calves was similar to that induced by the parent virus strain. The variant was shown to retain its characteristic cytopathic effect for Madin Darby bovine kidney cells and its property of hemagglutination following one passage in the natural host."} {"id": "PMID:163128", "title": "Utilization of triaryl phosphates by a mixed bacterial population.", "content": "A mixed bacterial population that has been isolated by enrichment culture is capable of growth on Fyrquel 220, a commercial triaryl phosphate lubricant, as sole carbon source. The mixture was dominated by a yellow, Gram-negative rod which made up greater than 60% of the mixture. However, all attempts to grow this organism in pure culture on triaryl phosphate were unsuccessful. The mixed population was also capable of growth on tri-o-cresyl phosphate, trixylenyl phosphate, and triphenyl phosphate as sole carbon sources. Viable cell numbers increased 20- to 30-fold, reaching a maximum after 72-96 h growth. Only a small portion of the triaryl phosphate was used for growth; the major part was emulsified and remained in the culture medium. No evidence of extracellular enzymes capable of triaryl phosphate degradation could be found in concentrates of the culture supernatant after growth, though traces of what may have been triaryl phosphate breakdown products were observed. Cell-free extracts of the mixed culture catalyzed the release of inorganic phosphate when incubated with Fyrquel 220, tri-o-cresyl phosphate, trixylenyl phosphate, or triphenyl phosphate, indicating the presence of a phosphotriesterase or of a phosphodiesterase of wide specificity.", "contents": "Utilization of triaryl phosphates by a mixed bacterial population. A mixed bacterial population that has been isolated by enrichment culture is capable of growth on Fyrquel 220, a commercial triaryl phosphate lubricant, as sole carbon source. The mixture was dominated by a yellow, Gram-negative rod which made up greater than 60% of the mixture. However, all attempts to grow this organism in pure culture on triaryl phosphate were unsuccessful. The mixed population was also capable of growth on tri-o-cresyl phosphate, trixylenyl phosphate, and triphenyl phosphate as sole carbon sources. Viable cell numbers increased 20- to 30-fold, reaching a maximum after 72-96 h growth. Only a small portion of the triaryl phosphate was used for growth; the major part was emulsified and remained in the culture medium. No evidence of extracellular enzymes capable of triaryl phosphate degradation could be found in concentrates of the culture supernatant after growth, though traces of what may have been triaryl phosphate breakdown products were observed. Cell-free extracts of the mixed culture catalyzed the release of inorganic phosphate when incubated with Fyrquel 220, tri-o-cresyl phosphate, trixylenyl phosphate, or triphenyl phosphate, indicating the presence of a phosphotriesterase or of a phosphodiesterase of wide specificity."} {"id": "PMID:163129", "title": "Composition of the capsular polysaccharides of Clostridium perfringens as a basis for their classification by chemotypes.", "content": "An analytical procedure, using gas-liquid chromatography, was developed for the identification of the per(trimethylsilyl) ethers of the constituent monosaccharides obtained from the capsular polysaccharides of Clostridium perfringens Hobbs 5, Hobbs 9, Hobbs 10, and NCTC 10578. Qualitative and quantitative differences between the major polysaccharide components enabled the differentiation of the four strains of C. perfringens investigated.", "contents": "Composition of the capsular polysaccharides of Clostridium perfringens as a basis for their classification by chemotypes. An analytical procedure, using gas-liquid chromatography, was developed for the identification of the per(trimethylsilyl) ethers of the constituent monosaccharides obtained from the capsular polysaccharides of Clostridium perfringens Hobbs 5, Hobbs 9, Hobbs 10, and NCTC 10578. Qualitative and quantitative differences between the major polysaccharide components enabled the differentiation of the four strains of C. perfringens investigated."} {"id": "PMID:163130", "title": "Conversion of spheroplast symbiotes in a leafhopper, Helochara communis Fitch (Cicadellidae: Homoptera).", "content": "In mycetomes of leafhoppers, Helochara communis, ultrastructural and histochemical studies revealed that spheroplast symbiotes (t-symbiotes) were converted to 'a-symbiotes' (so-called), with apparent loss of DNA--a phenomenon reminiscent of rhizobium-bacteroid conversion in certain legume nodules. Additional t-symbiotes were incorporated into the substance of these 'a-symbiotes'.", "contents": "Conversion of spheroplast symbiotes in a leafhopper, Helochara communis Fitch (Cicadellidae: Homoptera). In mycetomes of leafhoppers, Helochara communis, ultrastructural and histochemical studies revealed that spheroplast symbiotes (t-symbiotes) were converted to 'a-symbiotes' (so-called), with apparent loss of DNA--a phenomenon reminiscent of rhizobium-bacteroid conversion in certain legume nodules. Additional t-symbiotes were incorporated into the substance of these 'a-symbiotes'."} {"id": "PMID:163131", "title": "Progeny resulting from complementation between mutants of vesicular stomatitis virus.", "content": "The complementation properties of the virus progeny released from cells mixedly infected with mutants of vesicular stomatitis virus belonging to four different complementation groups have been examined. The group IV mutant, tsW16B, was tested in combinations with three group I mutants (tsW4, tsW28, and tsG11), one group II mutant (tsG22), and one group III mutant (tsW29). Virus stocks were grown from isolated plaques appearing on the cell monolayers used to assay the mixed infection yields and tested, in a second series of mixed infections, for their ability to complement each of the two parents. It was found that the virus harvested from each one of the first series of mixed infections contained mutants of both parental types.", "contents": "Progeny resulting from complementation between mutants of vesicular stomatitis virus. The complementation properties of the virus progeny released from cells mixedly infected with mutants of vesicular stomatitis virus belonging to four different complementation groups have been examined. The group IV mutant, tsW16B, was tested in combinations with three group I mutants (tsW4, tsW28, and tsG11), one group II mutant (tsG22), and one group III mutant (tsW29). Virus stocks were grown from isolated plaques appearing on the cell monolayers used to assay the mixed infection yields and tested, in a second series of mixed infections, for their ability to complement each of the two parents. It was found that the virus harvested from each one of the first series of mixed infections contained mutants of both parental types."} {"id": "PMID:163132", "title": "Cerebellar capillary hemangioblastoma: its histogenesis studied by organ culture and electron microscopy.", "content": "A capillary hemangioblastoma from the vermis of a 21-year-old man with von Hippel-Lindau's disease was successfully maintained in organ culture systems on Millipore filter platforms and gelatin sponge foam matrices up to 48 days. Three cell types--endothelial cells, pericytes, and stromal cells--identified by their fine structural features and their architectural relationships to vascular lumens and to the extracellular space were recognized in the original tumor. By light microscopy the explants showed, in the late stages, increased lipid droplets in the stromal cells and perivascular hyaline thickening. By electron microscopy, endothelial cells, pericytes, and stromal cells remained distinguishable as cell types. However, the stromal cells demonstrated, in addition to an increase of their normal complement of microfilaments and lipid droplets, features that were more characteristic of the two other cell types, i.e. micropinocytotic vesicles and the formation of zonula occludens junctions and hemidesmosomes. Basement membranes also became more apparent around the stromal cells. With increasing time in vitro, there was a striking increase in mature collagen fibers in the extracellular space. The roles of the different cell types in capillary hemangioblastoma and the histogenesis of the stromal cells are discussed in light of these observations. It is concluded that the capillary hemangioblastoma consists of multiple cell lines--endothelial cells, pericytes, stromal cells and, occasionally, hematopoietic cells--all of which are neoplastic and replicate in parallel with one another. Stromal cells may be regarded as an aberrant monopotential cell type which shares with the endothelial cell and pericyte a common mesenchymal, presumably angiogenic, ancestry, and may, on occasion, display morphological features, such as increased basement membrane formation and the formation of zonula occludens junctions, which recall its angiogenic lineage. However, interconvertibility between endothelial cells and stromal cells does not appear to occur in vivo or in vitro.", "contents": "Cerebellar capillary hemangioblastoma: its histogenesis studied by organ culture and electron microscopy. A capillary hemangioblastoma from the vermis of a 21-year-old man with von Hippel-Lindau's disease was successfully maintained in organ culture systems on Millipore filter platforms and gelatin sponge foam matrices up to 48 days. Three cell types--endothelial cells, pericytes, and stromal cells--identified by their fine structural features and their architectural relationships to vascular lumens and to the extracellular space were recognized in the original tumor. By light microscopy the explants showed, in the late stages, increased lipid droplets in the stromal cells and perivascular hyaline thickening. By electron microscopy, endothelial cells, pericytes, and stromal cells remained distinguishable as cell types. However, the stromal cells demonstrated, in addition to an increase of their normal complement of microfilaments and lipid droplets, features that were more characteristic of the two other cell types, i.e. micropinocytotic vesicles and the formation of zonula occludens junctions and hemidesmosomes. Basement membranes also became more apparent around the stromal cells. With increasing time in vitro, there was a striking increase in mature collagen fibers in the extracellular space. The roles of the different cell types in capillary hemangioblastoma and the histogenesis of the stromal cells are discussed in light of these observations. It is concluded that the capillary hemangioblastoma consists of multiple cell lines--endothelial cells, pericytes, stromal cells and, occasionally, hematopoietic cells--all of which are neoplastic and replicate in parallel with one another. Stromal cells may be regarded as an aberrant monopotential cell type which shares with the endothelial cell and pericyte a common mesenchymal, presumably angiogenic, ancestry, and may, on occasion, display morphological features, such as increased basement membrane formation and the formation of zonula occludens junctions, which recall its angiogenic lineage. However, interconvertibility between endothelial cells and stromal cells does not appear to occur in vivo or in vitro."} {"id": "PMID:163133", "title": "An assessment of the World Health Organization classification of the histologic typing of lung tumors applied to biopsy and resected material.", "content": "In a study of the World Health Organization classification of the histologic typing of lung tumors, sections from a total of 740 patients in the Medical Research Council Study of Cytotoxic Chemotherapy, 182 of whom also had positive preoperativebronchial biopsies and 231 involved lymph nodes in the resected specimens, and from 30 patients in the Medical Research Council Trial of Surgery and Radiotherapy in Small or Oat-celled Carcinoma of the Bronchus have been assessed. Of the 740 primary tumors from the Study of Cytotoxic Chemotherapy, 71% were placed in Type I, 12% in Type II, 9% in Type III, and 7% in Type IV. Only 2 primary tumors could not be typed. A blind comparison of the type of primary tumor and bronchial biopsy showed that the biopsy was a good indicator of the type of the primary tumor. A bind comparison of the primary tumor and involved lymph node also showed a close degree of agreement. However, when the type of the primary tumor was assessed in the presence of the involved node. Tumors were placed in Type IV far less frequently than when assessed blind. It is concluded that the World Health Organization classification is applicable to primary tumor, bronchial biopsy, and involved node, that the biopsy is a valuable indicator of the type of the primary tumor, and that the apparent type of the involved node should not be allowed to over-influence the pathologist in deciding on the type of the primary tumor when both are assessed together.", "contents": "An assessment of the World Health Organization classification of the histologic typing of lung tumors applied to biopsy and resected material. In a study of the World Health Organization classification of the histologic typing of lung tumors, sections from a total of 740 patients in the Medical Research Council Study of Cytotoxic Chemotherapy, 182 of whom also had positive preoperativebronchial biopsies and 231 involved lymph nodes in the resected specimens, and from 30 patients in the Medical Research Council Trial of Surgery and Radiotherapy in Small or Oat-celled Carcinoma of the Bronchus have been assessed. Of the 740 primary tumors from the Study of Cytotoxic Chemotherapy, 71% were placed in Type I, 12% in Type II, 9% in Type III, and 7% in Type IV. Only 2 primary tumors could not be typed. A blind comparison of the type of primary tumor and bronchial biopsy showed that the biopsy was a good indicator of the type of the primary tumor. A bind comparison of the primary tumor and involved lymph node also showed a close degree of agreement. However, when the type of the primary tumor was assessed in the presence of the involved node. Tumors were placed in Type IV far less frequently than when assessed blind. It is concluded that the World Health Organization classification is applicable to primary tumor, bronchial biopsy, and involved node, that the biopsy is a valuable indicator of the type of the primary tumor, and that the apparent type of the involved node should not be allowed to over-influence the pathologist in deciding on the type of the primary tumor when both are assessed together."} {"id": "PMID:163134", "title": "The glycolytic enzyme activity of the human cervix uteri.", "content": "The activity of the following enzymes was studied in normal, precancerous, and malignant biopsies from the human cervix uteri: hexokinase (HK), phosphofructokinase (PFK), pyruvate-kinase (PK), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G-6-PDH). In precancerous conditions, i.e., dysplasia and carcinoma in situ without any signs of invasive carcinoma, only PK showed moderate but significant activity increases. A rise in enzyme activity in biopsies histologically classified as carcinoma in situ was found to signal the presence of invasive carcinoma in other parts of the cervix. In invasive carcinomas of the cervix, all the enzymes studied showed a two- to four-fold increase (p less than 0.01) as compared to the normal cervix. The present study failed to reveal significant differences between enzyme activities in biopsies from patients in Stage I, II, and III; no correlation could be established between enzyme activity and prognosis.", "contents": "The glycolytic enzyme activity of the human cervix uteri. The activity of the following enzymes was studied in normal, precancerous, and malignant biopsies from the human cervix uteri: hexokinase (HK), phosphofructokinase (PFK), pyruvate-kinase (PK), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G-6-PDH). In precancerous conditions, i.e., dysplasia and carcinoma in situ without any signs of invasive carcinoma, only PK showed moderate but significant activity increases. A rise in enzyme activity in biopsies histologically classified as carcinoma in situ was found to signal the presence of invasive carcinoma in other parts of the cervix. In invasive carcinomas of the cervix, all the enzymes studied showed a two- to four-fold increase (p less than 0.01) as compared to the normal cervix. The present study failed to reveal significant differences between enzyme activities in biopsies from patients in Stage I, II, and III; no correlation could be established between enzyme activity and prognosis."} {"id": "PMID:163135", "title": "Cervical synovial sarcoma at the bifurcation of the carotid artery.", "content": "Cervical synovial sarcoma has been reported in only 15 cases; in none of these was there any association with a vascular structure. A patient with cervical synovial sarcoma encompassing the bifurcation of the left carotid artery underwent a left radical neck dissection, including excision of the left external carotid artery and the hypoglossal nerve. The tumor was dissected away from the common carotid and internal carotid arteries. Although the fibrous pseudocapsule of the tumor had not involved the fibrous adventitia of the carotid arteries. Radiation therapy with 6000 rads tumor dose was administered to a wide local field. There is no evidence of recurrence 1 year postoperatively. Histologic and ultrastructural findings were similar to those reported previously in a case of synovial sarcoma of an extremity.", "contents": "Cervical synovial sarcoma at the bifurcation of the carotid artery. Cervical synovial sarcoma has been reported in only 15 cases; in none of these was there any association with a vascular structure. A patient with cervical synovial sarcoma encompassing the bifurcation of the left carotid artery underwent a left radical neck dissection, including excision of the left external carotid artery and the hypoglossal nerve. The tumor was dissected away from the common carotid and internal carotid arteries. Although the fibrous pseudocapsule of the tumor had not involved the fibrous adventitia of the carotid arteries. Radiation therapy with 6000 rads tumor dose was administered to a wide local field. There is no evidence of recurrence 1 year postoperatively. Histologic and ultrastructural findings were similar to those reported previously in a case of synovial sarcoma of an extremity."} {"id": "PMID:163136", "title": "Salivary gland neoplasms following atomic radiation: additional cases and reanalysis of combined data in a fixed population, 1957-1970.", "content": "A reappraisal was made of the relationship between exposure to atomic radiation in 1945 and the occurrence of salivary gland tumors in heavily exposed survivors. This was made possible by the discovery of 8 additional patients; the total now reported consists of 30 cases. In those exposed to 300+ rads, the number of cases was significantly (p less than .01) greater than expected. This was found for the combined group and for malignant types, but not for histologically benign tumors. Our prior conclusion regarding the high-dose radiation effect upon salivary gland neoplasia remains unchanged in the reanalysis; however, our suggestion that younger persons were at significantly greater risk is weakened.", "contents": "Salivary gland neoplasms following atomic radiation: additional cases and reanalysis of combined data in a fixed population, 1957-1970. A reappraisal was made of the relationship between exposure to atomic radiation in 1945 and the occurrence of salivary gland tumors in heavily exposed survivors. This was made possible by the discovery of 8 additional patients; the total now reported consists of 30 cases. In those exposed to 300+ rads, the number of cases was significantly (p less than .01) greater than expected. This was found for the combined group and for malignant types, but not for histologically benign tumors. Our prior conclusion regarding the high-dose radiation effect upon salivary gland neoplasia remains unchanged in the reanalysis; however, our suggestion that younger persons were at significantly greater risk is weakened."} {"id": "PMID:163137", "title": "On the mechanism of hormone action in 7,12 dimethylbenz(a)anthracene-induced mammary tumor. I. Prolactin and progesterone effects on estrogen receptor in vitro.", "content": "The presence of ER in DMBA-tumors was demonstrated by the use of dextran-charcoal assay, sephadex chromatography, sucrose gradient sedimentation, and organ culture techniques. It was found that tumors have binding sites ranging from 10-13 to 10-15 moles/mg protein, and a dissociation constant of ER 10-9 to 10-10 M. In experiments with tumor explants, prolactin-insulin significantly stimulated ER binding capacity, as compared with control without prolactin. This stimulation was tissue-specific and inhibited by progesterone. Insulin had a synergistic effect on prolactin stimulation of ER. Our results presents a plausible explanation for tumor responses to these hormones in vivo. This interaction of prolactin, estrogen, and progesterone may be a common phenomenon for all estrogen-responsive tissues.", "contents": "On the mechanism of hormone action in 7,12 dimethylbenz(a)anthracene-induced mammary tumor. I. Prolactin and progesterone effects on estrogen receptor in vitro. The presence of ER in DMBA-tumors was demonstrated by the use of dextran-charcoal assay, sephadex chromatography, sucrose gradient sedimentation, and organ culture techniques. It was found that tumors have binding sites ranging from 10-13 to 10-15 moles/mg protein, and a dissociation constant of ER 10-9 to 10-10 M. In experiments with tumor explants, prolactin-insulin significantly stimulated ER binding capacity, as compared with control without prolactin. This stimulation was tissue-specific and inhibited by progesterone. Insulin had a synergistic effect on prolactin stimulation of ER. Our results presents a plausible explanation for tumor responses to these hormones in vivo. This interaction of prolactin, estrogen, and progesterone may be a common phenomenon for all estrogen-responsive tissues."} {"id": "PMID:163138", "title": "Thymus-dependent lymphocyte levels in bronchogenic carcinoma: correlations with histology, clinical stage, and clinical course after surgical treatment.", "content": "The in vitro spontaneous lymphocyte rosette (T cell) assay was used to determine cellular immunologic competence in 112 patients with bronchogenic carcinoma. Among preoperative patients with localized tumors. T cell levels were significantly lower than in 237 normal controls. With advanced stages of disease, T cell levels declined progressively among patients with squamous cell carcinoma, oat cell carcinoma, and undifferentiated carcinoma, but not among patients with adenocarcinoma. Squamous carcinoma patients considered cured had persisting low T cell levels, but cured adenocarcinoma patients had normal levels. Serial determinations that showed a fall in T cell levels preceded the development of clinically evident metastases by an average of 2.5 months. Postoperative patients with rising T cell levels have remained clinically free of disease. The data indicate that T cell levels correlate with extent of tumor and clinical course of patients with bronchogenic carcinoma. The assay may, therefore, provide a rational basis for the selection of patients who are at high risk for the development of recurrence after surgical resection and who may benefit from the early institution of adjunctive therapy.", "contents": "Thymus-dependent lymphocyte levels in bronchogenic carcinoma: correlations with histology, clinical stage, and clinical course after surgical treatment. The in vitro spontaneous lymphocyte rosette (T cell) assay was used to determine cellular immunologic competence in 112 patients with bronchogenic carcinoma. Among preoperative patients with localized tumors. T cell levels were significantly lower than in 237 normal controls. With advanced stages of disease, T cell levels declined progressively among patients with squamous cell carcinoma, oat cell carcinoma, and undifferentiated carcinoma, but not among patients with adenocarcinoma. Squamous carcinoma patients considered cured had persisting low T cell levels, but cured adenocarcinoma patients had normal levels. Serial determinations that showed a fall in T cell levels preceded the development of clinically evident metastases by an average of 2.5 months. Postoperative patients with rising T cell levels have remained clinically free of disease. The data indicate that T cell levels correlate with extent of tumor and clinical course of patients with bronchogenic carcinoma. The assay may, therefore, provide a rational basis for the selection of patients who are at high risk for the development of recurrence after surgical resection and who may benefit from the early institution of adjunctive therapy."} {"id": "PMID:163139", "title": "\"Residual\" mammary carcinoma following simulated partial mastectomy.", "content": "Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25-35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.", "contents": "\"Residual\" mammary carcinoma following simulated partial mastectomy. Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25-35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy."} {"id": "PMID:163140", "title": "The genetics of childhood cancer.", "content": "Retinoblastoma should not be considered as the exceptional childhood cancer that shows dominant inheritance, but rather as the typical childhood cancer that embraces a prezygotic and postzygotic subgroup. Postzygotic cases are conceived as involving mutation as a first step too, but with the mutation in somatic rather than germinal cells. In both prezygotic and postzygotic cases a second event, possibly mutational, occurs before the cancer is initiated. The embryonal cancers are all visualized as genetic disease, and their frequencies limited by gene mutability. This mutability can be increased by environmental agents. Prezygotic cases may develop other primary tumors in other tissues. They may also have affected family members, the probability of affected offspring approaching 50%. A diagnostic test to identify prezygotic cases among those with a single primary tumor and a negative family history is sorely needed.", "contents": "The genetics of childhood cancer. Retinoblastoma should not be considered as the exceptional childhood cancer that shows dominant inheritance, but rather as the typical childhood cancer that embraces a prezygotic and postzygotic subgroup. Postzygotic cases are conceived as involving mutation as a first step too, but with the mutation in somatic rather than germinal cells. In both prezygotic and postzygotic cases a second event, possibly mutational, occurs before the cancer is initiated. The embryonal cancers are all visualized as genetic disease, and their frequencies limited by gene mutability. This mutability can be increased by environmental agents. Prezygotic cases may develop other primary tumors in other tissues. They may also have affected family members, the probability of affected offspring approaching 50%. A diagnostic test to identify prezygotic cases among those with a single primary tumor and a negative family history is sorely needed."} {"id": "PMID:163141", "title": "The evaluation of abdominal masses in children with emphasis on noninvasive methods. A roentgenographic approach.", "content": "Intravenous urography with total body opacification, and tomography as required, often give the most information toward evaluating abdominal masses in children. Ultrasonography is a noninvasive procedure which defines normal structures and differentiates cystic and solid tumors. The combination of these studies gives sufficient information about renal tumors to plan for possible surgery. Arteriography is not necessary for the diagnosis of Wilms' tumor, nor its surgical or medical management. Pseudotumor of the kidney is due to focal cortical hyperplasia. It can be diagnosed by nephrotomography, renal arteriography or renal scanning. The latter method is most accurate and has the lowest morbidity. Aortography is advisable in the evaluation of a patient with pheochromocytoma in an attempt to locate multiple tumors. Determining the extent of abdominal neuroblastoma by angiography and lymphangiography does not appear to influence the mode of therapy, not the survival rate; therefore, invasive diagnostic procedures do not appear to be indicated in neuroblastoma. Angiography is necessary in the evaluation of liver cancer. If one lobe is determined to be free of disease, lobectomy is a possible cure. Splenic cysts and choledochal cysts can be diagnosed by noninvasive methods such as ultrasonography or radioisotope scanning. Arteriography and percutaneous opacification are not necessary to make these diagnoses.", "contents": "The evaluation of abdominal masses in children with emphasis on noninvasive methods. A roentgenographic approach. Intravenous urography with total body opacification, and tomography as required, often give the most information toward evaluating abdominal masses in children. Ultrasonography is a noninvasive procedure which defines normal structures and differentiates cystic and solid tumors. The combination of these studies gives sufficient information about renal tumors to plan for possible surgery. Arteriography is not necessary for the diagnosis of Wilms' tumor, nor its surgical or medical management. Pseudotumor of the kidney is due to focal cortical hyperplasia. It can be diagnosed by nephrotomography, renal arteriography or renal scanning. The latter method is most accurate and has the lowest morbidity. Aortography is advisable in the evaluation of a patient with pheochromocytoma in an attempt to locate multiple tumors. Determining the extent of abdominal neuroblastoma by angiography and lymphangiography does not appear to influence the mode of therapy, not the survival rate; therefore, invasive diagnostic procedures do not appear to be indicated in neuroblastoma. Angiography is necessary in the evaluation of liver cancer. If one lobe is determined to be free of disease, lobectomy is a possible cure. Splenic cysts and choledochal cysts can be diagnosed by noninvasive methods such as ultrasonography or radioisotope scanning. Arteriography and percutaneous opacification are not necessary to make these diagnoses."} {"id": "PMID:163142", "title": "Advances in the treatment of Wilms' tumor.", "content": "The addition of chemotherapy to older standard treatment with surgery and radiotherapy has increased survival to more than 80% in localized Wilms' tumor, and about 50% in metastatic disease. Actinomycin-D and vincristine have proved to be the two most active agents. Multiple-course maintenance treatment with actinomycin-D has allowed fewer relapses, but not a significantly different survival rate than a single course of this drug. Use of actinomycin-D and vincristine in combination has been under study; initial indications show that the combination is superior to either drug employed singly. The need for postoperative radiotherapy in totally resected tumors confined to the kidney is also under study. Adriamycin is at present the most encouraging new drug that has had clinical trial.", "contents": "Advances in the treatment of Wilms' tumor. The addition of chemotherapy to older standard treatment with surgery and radiotherapy has increased survival to more than 80% in localized Wilms' tumor, and about 50% in metastatic disease. Actinomycin-D and vincristine have proved to be the two most active agents. Multiple-course maintenance treatment with actinomycin-D has allowed fewer relapses, but not a significantly different survival rate than a single course of this drug. Use of actinomycin-D and vincristine in combination has been under study; initial indications show that the combination is superior to either drug employed singly. The need for postoperative radiotherapy in totally resected tumors confined to the kidney is also under study. Adriamycin is at present the most encouraging new drug that has had clinical trial."} {"id": "PMID:163143", "title": "Radiation therapy of tumors of the central nervous system in childhood.", "content": "The results of radiation therapy for CNS tumors of childhood are presented and discussed according to histologic type. In this material the 5-year recurrence-free survival rates were about 35% for medulloblastomas, 48% for the hypothalamic and brain stem tumors, 86% for lowgrade ependymomas, and 57% for germinomas. Complications or CNS injury from irradiation were rare and the quality of life in survivors was generally good. Current methods of radiation therapy may possibly improve these results. Tumors of the CNS in children do not necessarily carry a hopeless prognosis; aggressive therapy is indicated.", "contents": "Radiation therapy of tumors of the central nervous system in childhood. The results of radiation therapy for CNS tumors of childhood are presented and discussed according to histologic type. In this material the 5-year recurrence-free survival rates were about 35% for medulloblastomas, 48% for the hypothalamic and brain stem tumors, 86% for lowgrade ependymomas, and 57% for germinomas. Complications or CNS injury from irradiation were rare and the quality of life in survivors was generally good. Current methods of radiation therapy may possibly improve these results. Tumors of the CNS in children do not necessarily carry a hopeless prognosis; aggressive therapy is indicated."} {"id": "PMID:163151", "title": "Dissociations between changes in myocardial cyclic adenosine monophosphate and contractility.", "content": "The relationship between changes in the myocardial concentration of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and cardiac contractility was studied in guinea pig and rat myocardium. When isolated perfused guinea pig heart were perfused with 10-5-M papaverine, a potent inhibitor of cyclic AMP phosphodiesterase activity, myocardial cyclic AMP concentration increased significantly from 1.7 plus and minus 0.2 (SE) pmoles/mg protein (N equal 12) to 3.3 plus and minus 0.2 pmoles/mg protein (N equal 12), and the percent of phosphorylase aual 6) (P less than 0.01). However, perfusion with papaverine had no effect on contractility in the absence or the presence of exogenous epinephrine. In perfused rat hearts, 10-5 M glucagon increased myocardial cyclic AMP concentration from 1.5 plus and minus 0.1 pmoles/mg protein (N equal 12) to 2.6 plus and minus 0.1 pmoles/mg protein (N equal 12) (P less than 0.001). In contrast, cyclic AMP levels did not increase detectably in guinea pig heart perfused with glucagon. Glucagon increased adenylate cyclase activity more than twofold in rat myocardial broken cell preparations but failed to stimulate the enzyme in preparations from guinea pigs. Despite these differences, the positive inotropic effects of glucagon on rat and guinea pig hearts were very similar over a wide dose range. Thus, with both papaverine and glucagon, changes in cardiac contractility were dissociated from stimulation of adenylate cyclase activity, increases in myocardial cyclic AMP levels, and conversion of phosphorylase b to phosphorylase a in perfused hearts.", "contents": "Dissociations between changes in myocardial cyclic adenosine monophosphate and contractility. The relationship between changes in the myocardial concentration of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and cardiac contractility was studied in guinea pig and rat myocardium. When isolated perfused guinea pig heart were perfused with 10-5-M papaverine, a potent inhibitor of cyclic AMP phosphodiesterase activity, myocardial cyclic AMP concentration increased significantly from 1.7 plus and minus 0.2 (SE) pmoles/mg protein (N equal 12) to 3.3 plus and minus 0.2 pmoles/mg protein (N equal 12), and the percent of phosphorylase aual 6) (P less than 0.01). However, perfusion with papaverine had no effect on contractility in the absence or the presence of exogenous epinephrine. In perfused rat hearts, 10-5 M glucagon increased myocardial cyclic AMP concentration from 1.5 plus and minus 0.1 pmoles/mg protein (N equal 12) to 2.6 plus and minus 0.1 pmoles/mg protein (N equal 12) (P less than 0.001). In contrast, cyclic AMP levels did not increase detectably in guinea pig heart perfused with glucagon. Glucagon increased adenylate cyclase activity more than twofold in rat myocardial broken cell preparations but failed to stimulate the enzyme in preparations from guinea pigs. Despite these differences, the positive inotropic effects of glucagon on rat and guinea pig hearts were very similar over a wide dose range. Thus, with both papaverine and glucagon, changes in cardiac contractility were dissociated from stimulation of adenylate cyclase activity, increases in myocardial cyclic AMP levels, and conversion of phosphorylase b to phosphorylase a in perfused hearts."} {"id": "PMID:163152", "title": "Catecholamine-dependent cyclic adenosine monophosphate and renin in the dog kidney.", "content": "Lithium inhibits the catecholamine-dependent cyclic adenosine monophosphate (AMP) generation in the kidney but not the hemodynamic effects of beta-adrenergic stimulation. Therefore, the possible role of catecholamine-dependent cyclic AMP in the release of renin was investigated in lithium-treated dogs both in vivo and vitro. Lithium therapy had no measurable effect on the increase in plasma renin activity induced by an injection of isoproterenol (2.6 plus and minus 1.2 (SE) ng/hour in control dogs vs. 3.0 plus and minus 1.2 ng/hour in lithium-treated dogs, P greater than 0.05). However, lithium inhibited the isoproterenol-induced increase in urinary excretion of cyclic AMP in vivo (791 plus and minus 199 pmoles/min in control dogs vs. 123 plus and minus 129 pmoles/min in lithium-treated dogs, P less than 0.05) and the increase in cyclic AMP concentration in renal tissue in vitro (4.50 plus and minus 0.15 pmoles/ng wet tissue in control dogs vs. 0.34 plus and minus 0.26 pmoles/mg in lithium-treated dogs, P less than 0.01). The finding that, in the lithium-treated dogs, isoproternol increased plasma renin activity but not cyclic AMP generation in the kidney suggests that the increase in plasma renin activity observed after an injection of isoproterenol is probably not mediated through the beta-adrenergic stimulus-dependent cyclic AMP system in the kidney.", "contents": "Catecholamine-dependent cyclic adenosine monophosphate and renin in the dog kidney. Lithium inhibits the catecholamine-dependent cyclic adenosine monophosphate (AMP) generation in the kidney but not the hemodynamic effects of beta-adrenergic stimulation. Therefore, the possible role of catecholamine-dependent cyclic AMP in the release of renin was investigated in lithium-treated dogs both in vivo and vitro. Lithium therapy had no measurable effect on the increase in plasma renin activity induced by an injection of isoproterenol (2.6 plus and minus 1.2 (SE) ng/hour in control dogs vs. 3.0 plus and minus 1.2 ng/hour in lithium-treated dogs, P greater than 0.05). However, lithium inhibited the isoproterenol-induced increase in urinary excretion of cyclic AMP in vivo (791 plus and minus 199 pmoles/min in control dogs vs. 123 plus and minus 129 pmoles/min in lithium-treated dogs, P less than 0.05) and the increase in cyclic AMP concentration in renal tissue in vitro (4.50 plus and minus 0.15 pmoles/ng wet tissue in control dogs vs. 0.34 plus and minus 0.26 pmoles/mg in lithium-treated dogs, P less than 0.01). The finding that, in the lithium-treated dogs, isoproternol increased plasma renin activity but not cyclic AMP generation in the kidney suggests that the increase in plasma renin activity observed after an injection of isoproterenol is probably not mediated through the beta-adrenergic stimulus-dependent cyclic AMP system in the kidney."} {"id": "PMID:163153", "title": "Comparative uptake of rat and human serum low-density and high-density lipoproteins by rat aortic smooth muscle cells in culture.", "content": "Rat aortic smooth muscle cells in culture were exposed to rat and human serum (LDL) and high-density (HDL) lipoproteins labeled with 125-I. 125-I-lipid was taken up preferentially from all of the lipoproteins used. 125-I-protein uptake of both rat LDL and HDL was significantly higher than that of the corresponding human lipoproteins, and human LDL was preferred to human HDL. The uptake of delipidated high-density apolipoproteins of either rat or human origin was very low. About 3-4% of the interiorized rat LDL and HDL was catabolized during 48 hours of incubation. On electron microscopic autoradiography of cells incubated with rat 125-I-LDL, the concentration of label, representing mainly 125-I-protein, was associated with secondary lysosomes. These results suggest that, if the protein uptake represents particle uptake, the preferential uptake of human LDL compared with human HDL could account in part for the finding that LDL acts as a more potent feedback suppressor of 3-hydroxy-3-methylglutaryl CoA reductase than does HDL.", "contents": "Comparative uptake of rat and human serum low-density and high-density lipoproteins by rat aortic smooth muscle cells in culture. Rat aortic smooth muscle cells in culture were exposed to rat and human serum (LDL) and high-density (HDL) lipoproteins labeled with 125-I. 125-I-lipid was taken up preferentially from all of the lipoproteins used. 125-I-protein uptake of both rat LDL and HDL was significantly higher than that of the corresponding human lipoproteins, and human LDL was preferred to human HDL. The uptake of delipidated high-density apolipoproteins of either rat or human origin was very low. About 3-4% of the interiorized rat LDL and HDL was catabolized during 48 hours of incubation. On electron microscopic autoradiography of cells incubated with rat 125-I-LDL, the concentration of label, representing mainly 125-I-protein, was associated with secondary lysosomes. These results suggest that, if the protein uptake represents particle uptake, the preferential uptake of human LDL compared with human HDL could account in part for the finding that LDL acts as a more potent feedback suppressor of 3-hydroxy-3-methylglutaryl CoA reductase than does HDL."} {"id": "PMID:163155", "title": "Improved method for densitometry of electrophoretic lipoprotein fraction.", "content": "We evaluated a method for the densitometric quantitation of the electrophoretic lipoprotein fractions that sets the limit of integration at the beta-lipoprotein peak maximum. Results were compared with the more conventional method of placing the limit of integration in the valley between the beta- and pre-beta-lipoprotein peaks. The criterion of symmetrical beta-lipoprotein peaks imposed by the method was tested, and manual determination of the beta peak maximum was compared to automatic computer analysis. Computer-generated curves stimulating increasing overlap of constant shape beta and pre-beta peaks were analyzed by the two methods. The conventional method introduces an error that increases with increasing overlap, but with the present method results agreed with those for completely resolved peaks. The beta peak was best approximated by an isosceles triangle (at least for the electrophoresis technique used in these studies), indicating symmetry of the beta peak. Values for the area under the lipoprotein peaks obtained by manual and computer placement of the integration limits agreed well (gamma = .892 to .998; SE of estimate = .0264 to .0306). The \"beta peak maximum\" method of densitometric quantitation avoids the problems associated with partial resolution of the beta- and pre-beta-lipoproteins. It is equally adaptable to either visual placement of the limits of integration or computer analysis.", "contents": "Improved method for densitometry of electrophoretic lipoprotein fraction. We evaluated a method for the densitometric quantitation of the electrophoretic lipoprotein fractions that sets the limit of integration at the beta-lipoprotein peak maximum. Results were compared with the more conventional method of placing the limit of integration in the valley between the beta- and pre-beta-lipoprotein peaks. The criterion of symmetrical beta-lipoprotein peaks imposed by the method was tested, and manual determination of the beta peak maximum was compared to automatic computer analysis. Computer-generated curves stimulating increasing overlap of constant shape beta and pre-beta peaks were analyzed by the two methods. The conventional method introduces an error that increases with increasing overlap, but with the present method results agreed with those for completely resolved peaks. The beta peak was best approximated by an isosceles triangle (at least for the electrophoresis technique used in these studies), indicating symmetry of the beta peak. Values for the area under the lipoprotein peaks obtained by manual and computer placement of the integration limits agreed well (gamma = .892 to .998; SE of estimate = .0264 to .0306). The \"beta peak maximum\" method of densitometric quantitation avoids the problems associated with partial resolution of the beta- and pre-beta-lipoproteins. It is equally adaptable to either visual placement of the limits of integration or computer analysis."} {"id": "PMID:163156", "title": "Determination of diphenylhydantoin in human serum by spin immunoassay.", "content": "A spinn immunoassay for diphenylhydantoin is reported, which appears to give an accurate and precise estimate of serum diphenylhydantoin concentrations, as judged by the disappearance of [14C]diphenylhydantoin from the serum of a rabbit. The assay also appears to be a reliable technique for routine diphenylhydantoin determinations, as judged from our experience with 28 patients. Serum diphenylhydantoin concentrations in the range of 1.0-50.0 mg/liter are easily determined on a 50-mul sample. Except for primidone, no significant cross reactivity was observed with eight drugs that are commonly used in conjunction with diphenylhydantoin therapy. This fast, simple, and precise method therefore appears to be readily applicable to routine determination of diphenylhydantoin.", "contents": "Determination of diphenylhydantoin in human serum by spin immunoassay. A spinn immunoassay for diphenylhydantoin is reported, which appears to give an accurate and precise estimate of serum diphenylhydantoin concentrations, as judged by the disappearance of [14C]diphenylhydantoin from the serum of a rabbit. The assay also appears to be a reliable technique for routine diphenylhydantoin determinations, as judged from our experience with 28 patients. Serum diphenylhydantoin concentrations in the range of 1.0-50.0 mg/liter are easily determined on a 50-mul sample. Except for primidone, no significant cross reactivity was observed with eight drugs that are commonly used in conjunction with diphenylhydantoin therapy. This fast, simple, and precise method therefore appears to be readily applicable to routine determination of diphenylhydantoin."} {"id": "PMID:163157", "title": "Serum and erythocyte argininosuccinate lyase assay by NADH fluorescence generated from formed fumarate.", "content": "Measurement of argininosuccinase (I; EC 4.3.2.1) activity is useful in following the course of disease in hepatitis and in screening for the genetic defect, argininosuccinic aciduria. Methodology is proposed for a novel procedure for the determination of I in serum and erythrocytes. In the procedure, fumarate, generated in the reaction, is assayed by conversion to malate with fumarase, determining the malate enzymatically with malate dehydrogenase, and estimating the NADH formed spectrofluorometrically. By this procedure, the enzyme activity in serum from normal individuals is less than 11 mumol/liter of erthrocytes/per hour. The correlation coefficient between results by this method and by the colorimetric method, which measures the arginine generated in the reaction, is +0.97 for serum and +0.98 for erythrocytes. The proposed procedure has a relatively low initial blank, requires less serum, and is completed faster.", "contents": "Serum and erythocyte argininosuccinate lyase assay by NADH fluorescence generated from formed fumarate. Measurement of argininosuccinase (I; EC 4.3.2.1) activity is useful in following the course of disease in hepatitis and in screening for the genetic defect, argininosuccinic aciduria. Methodology is proposed for a novel procedure for the determination of I in serum and erythrocytes. In the procedure, fumarate, generated in the reaction, is assayed by conversion to malate with fumarase, determining the malate enzymatically with malate dehydrogenase, and estimating the NADH formed spectrofluorometrically. By this procedure, the enzyme activity in serum from normal individuals is less than 11 mumol/liter of erthrocytes/per hour. The correlation coefficient between results by this method and by the colorimetric method, which measures the arginine generated in the reaction, is +0.97 for serum and +0.98 for erythrocytes. The proposed procedure has a relatively low initial blank, requires less serum, and is completed faster."} {"id": "PMID:163159", "title": "Mechanized enzymatic determination of triglycerides in serum.", "content": "A procedure for enzymatic determination of serum triglycerides [Clin. Chem. 19, 476 (1973)] has been adapted for use in continuous-flow analysis (Technicon AutoAnalyzer). A very simple manifold is used; serum is incubated at 37 degrees C with the lipase and alpha-chymotrypsin in potassium phosphate buffer (0.1 mol/liter, pH 7, containing 1.50 g of bovine serum albumin per liter). The liberated glycerol is dialyzed against the complete glycerol reagent. The change in absorbance at 340 nm resulting from oxidation of NADH is proportional to the dialyzed glycerol. The same manifold can be used to determine preformed glycerol if the hydrolyzing enzymes are omitted. The hydrolysis is complete, as shown by the use of equivalent glycerol standards. No prior treatment of the samples is necessary. Assays are run at 60 per hour in the AutoAnalyzer l, 80 per hour in the AutoAnalyzer ll. Results with both instruments for 150 samples correlated well with those obtained by the same enzymatic manual method and by the AutoAnalyzer fluorometric procedure.", "contents": "Mechanized enzymatic determination of triglycerides in serum. A procedure for enzymatic determination of serum triglycerides [Clin. Chem. 19, 476 (1973)] has been adapted for use in continuous-flow analysis (Technicon AutoAnalyzer). A very simple manifold is used; serum is incubated at 37 degrees C with the lipase and alpha-chymotrypsin in potassium phosphate buffer (0.1 mol/liter, pH 7, containing 1.50 g of bovine serum albumin per liter). The liberated glycerol is dialyzed against the complete glycerol reagent. The change in absorbance at 340 nm resulting from oxidation of NADH is proportional to the dialyzed glycerol. The same manifold can be used to determine preformed glycerol if the hydrolyzing enzymes are omitted. The hydrolysis is complete, as shown by the use of equivalent glycerol standards. No prior treatment of the samples is necessary. Assays are run at 60 per hour in the AutoAnalyzer l, 80 per hour in the AutoAnalyzer ll. Results with both instruments for 150 samples correlated well with those obtained by the same enzymatic manual method and by the AutoAnalyzer fluorometric procedure."} {"id": "PMID:163161", "title": "Rapid radioimmunoassay of carcinoembryonic antigen (CEA) in ultrafiltered perchloric acid extracts: results of a clinical survey.", "content": "Perchloric acid treatment of the carcinoembryonic antigen (CEA) results in subunits of approximate mol. wt 40 000 to 50 000 with different electrophoretic mobilities and amtogenic deficiences as demonstrated by immunoelectrophoresis. An improved radioimmunoassay is described for the quantitation of CEA using rapid ultrafiltration of serum or plasma extracts. The assay was designed to take into account the changes CEA undergoes during perchloric acid extraction. Absorption of antibodies against a crossreacting non-specific antigen from CEA antiserum did not improve the specificity of the radioimmunoassay as was shown by clinical use of the test in almost 1800 patients.", "contents": "Rapid radioimmunoassay of carcinoembryonic antigen (CEA) in ultrafiltered perchloric acid extracts: results of a clinical survey. Perchloric acid treatment of the carcinoembryonic antigen (CEA) results in subunits of approximate mol. wt 40 000 to 50 000 with different electrophoretic mobilities and amtogenic deficiences as demonstrated by immunoelectrophoresis. An improved radioimmunoassay is described for the quantitation of CEA using rapid ultrafiltration of serum or plasma extracts. The assay was designed to take into account the changes CEA undergoes during perchloric acid extraction. Absorption of antibodies against a crossreacting non-specific antigen from CEA antiserum did not improve the specificity of the radioimmunoassay as was shown by clinical use of the test in almost 1800 patients."} {"id": "PMID:163165", "title": "Plasma adenosine 3':5'-cyclic monophosphate response to glucagon in thyroid disease.", "content": "1. The plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to intravenously administered glucagon has been studied in nine hyperthyroid, five hypothyroid and ten euthyroid patients. 2. Concentrations of the nucleotide rose to a peak at 15 min and declined to near basal values by 120 min, the response being greatest in hyperthyroid and least in hypothyroid subjects. The mean peak concentrations were 1028 nmol/1 in the hyperthyroid group, 252 nmol/1 in the hypothyroid group and 534 nmol/1 in the euthyroid group. 3. These results could not be accounted for by differences in serum insulin response. 4. It is suggested that the response of plasma cyclic AMP to glucagon may serve as an index of tissue thyroid status.", "contents": "Plasma adenosine 3':5'-cyclic monophosphate response to glucagon in thyroid disease. 1. The plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to intravenously administered glucagon has been studied in nine hyperthyroid, five hypothyroid and ten euthyroid patients. 2. Concentrations of the nucleotide rose to a peak at 15 min and declined to near basal values by 120 min, the response being greatest in hyperthyroid and least in hypothyroid subjects. The mean peak concentrations were 1028 nmol/1 in the hyperthyroid group, 252 nmol/1 in the hypothyroid group and 534 nmol/1 in the euthyroid group. 3. These results could not be accounted for by differences in serum insulin response. 4. It is suggested that the response of plasma cyclic AMP to glucagon may serve as an index of tissue thyroid status."} {"id": "PMID:163168", "title": "Metabolism, function and clinical aspects of vitamin D.", "content": "Briefly reviewed herein are some of the contemporary findings on the metabolism of vitamin D, and the biochemical and physiological effects of this steroid in the animal. Certainly the most accepted major action of vitamin D is to enhance the intestinal absorption of calcium. Historically, there is also considerable evidence that the vitamin D is required for the resorption of calcium from bone, thereby aiding in maintaining normal serum calcium levels. Increasing evidence is becoming available that vitamin D does have a direct effect at the kidney level, and that the absorption and metabolism of the phosphate ion is also significantly affected by this steroid. As a consequence of vitamin D administration to the rachitic animal, some molecular changes in the intestine have been identified and these include the induction of the vitamin D dependent calcium binding protein, an increase in intestinal levels of alkaline phosphatase and calcium ATPase, and a stimulation of the adenylate cyclase system. A hallmark of recent efforts is a further understanding of the metabolism of vitamin D and the formation of its most active form, 1,25-dihydroxycholecalciferol. All of this knowledge will prove valuable in the rational treatment of certain abnormalities of calcium and bone metabolism for which examples are already available.", "contents": "Metabolism, function and clinical aspects of vitamin D. Briefly reviewed herein are some of the contemporary findings on the metabolism of vitamin D, and the biochemical and physiological effects of this steroid in the animal. Certainly the most accepted major action of vitamin D is to enhance the intestinal absorption of calcium. Historically, there is also considerable evidence that the vitamin D is required for the resorption of calcium from bone, thereby aiding in maintaining normal serum calcium levels. Increasing evidence is becoming available that vitamin D does have a direct effect at the kidney level, and that the absorption and metabolism of the phosphate ion is also significantly affected by this steroid. As a consequence of vitamin D administration to the rachitic animal, some molecular changes in the intestine have been identified and these include the induction of the vitamin D dependent calcium binding protein, an increase in intestinal levels of alkaline phosphatase and calcium ATPase, and a stimulation of the adenylate cyclase system. A hallmark of recent efforts is a further understanding of the metabolism of vitamin D and the formation of its most active form, 1,25-dihydroxycholecalciferol. All of this knowledge will prove valuable in the rational treatment of certain abnormalities of calcium and bone metabolism for which examples are already available."} {"id": "PMID:163170", "title": "Phospholipid biosynthesis: the activity of phosphatidic acid phosphohydrolase in the developing lung and amnionic fluid.", "content": "The presented data suggest that PAPase may, indeed, be important in the biosynthesis of lung phospholipids. The observed increase in the specific activity of rabbit lung precedes the \"surge\" of phosphatidylcholine concentration and surfactant biosynthesis by at least 24 hours. In human amnionic fluid, PAPase specific activity was markedly increased in pregnancies of 35 weeks of gestation or more. The increase in the specific activity of PAPase preceded the \"surge\" of acetone precipitated phosphatidylcholine. The reported studies may provide an additional procedure to examine the problems associated with surfactant biosynthesis.", "contents": "Phospholipid biosynthesis: the activity of phosphatidic acid phosphohydrolase in the developing lung and amnionic fluid. The presented data suggest that PAPase may, indeed, be important in the biosynthesis of lung phospholipids. The observed increase in the specific activity of rabbit lung precedes the \"surge\" of phosphatidylcholine concentration and surfactant biosynthesis by at least 24 hours. In human amnionic fluid, PAPase specific activity was markedly increased in pregnancies of 35 weeks of gestation or more. The increase in the specific activity of PAPase preceded the \"surge\" of acetone precipitated phosphatidylcholine. The reported studies may provide an additional procedure to examine the problems associated with surfactant biosynthesis."} {"id": "PMID:163171", "title": "Functional evaluation of lung mitochondria.", "content": "Activity of lung mitochondria was studied with a preparation of isolated mitochondria. This was correlated with responses of the isolated perfused lung as determined from surface fluorescence measurements and tissue redox couples. Lung mitochondria demonstrated substrate oxidation, respiratory control, and Caplus plus activation of alpha-glycerophosphate dehydrogenase. In response to oxidative inhibitors, the isolated lung showed increased surface fluorescence and increased tissue ratios of redox couples indicating reduction of pyridine nucleotides. The results demonstrate functional activity of lung mitochondria in situ.", "contents": "Functional evaluation of lung mitochondria. Activity of lung mitochondria was studied with a preparation of isolated mitochondria. This was correlated with responses of the isolated perfused lung as determined from surface fluorescence measurements and tissue redox couples. Lung mitochondria demonstrated substrate oxidation, respiratory control, and Caplus plus activation of alpha-glycerophosphate dehydrogenase. In response to oxidative inhibitors, the isolated lung showed increased surface fluorescence and increased tissue ratios of redox couples indicating reduction of pyridine nucleotides. The results demonstrate functional activity of lung mitochondria in situ."} {"id": "PMID:163173", "title": "Pharmacologic regulation of alveolar surfactant in fetal and newborn rabbits: ACTH, heroin, isoxsuprine, and glucocorticoid.", "content": "The evidence that pharmacologic doses of glucocorticoids induce lung maturation and diminish risk of respiratory distress syndrome has been reviewed briefly. Studies with heroin corroborate that pharmacologic induction of lung maturation is possible in the human fetus. Endogenous fetal glucocorticoids may serve as a physiologic mechanism that prepares the immature lungs for birth. Catecholamines may induce release of stored surfactant from type 2 cells into alveolar spaces.", "contents": "Pharmacologic regulation of alveolar surfactant in fetal and newborn rabbits: ACTH, heroin, isoxsuprine, and glucocorticoid. The evidence that pharmacologic doses of glucocorticoids induce lung maturation and diminish risk of respiratory distress syndrome has been reviewed briefly. Studies with heroin corroborate that pharmacologic induction of lung maturation is possible in the human fetus. Endogenous fetal glucocorticoids may serve as a physiologic mechanism that prepares the immature lungs for birth. Catecholamines may induce release of stored surfactant from type 2 cells into alveolar spaces."} {"id": "PMID:163177", "title": "[Investigations on immunity against poliomyelitis (author's transl)].", "content": "Six virus laboratories from various parts of the German Federal Republic and West Berlin undertook investigations into polio-myelitis immunity in 1972. A total of 267 persons aged up to 20 years were investigated for neutralizing antibodies against the three types of polio virus. The study showed that from the fourth year of life approximately 70% of the persons investigated had antibodies against all three types of polio virus. In some younger children the equivalent values were considerably lower. After the fourth year of life there were only slight differences in the humoral immunity against the three polio virus types. There was no evidence that the immunity level had deteriorated up to the 20th year of life and thus there is no indication of the necessity for a repeat immunisation at a certain time. The investigation confirmed that three oral administrations of trivalent vaccine, as are now generally recommended as basic immunization in the German Federal Republic, result in a conversion rate of over 90% against each of the three virus types.", "contents": "[Investigations on immunity against poliomyelitis (author's transl)]. Six virus laboratories from various parts of the German Federal Republic and West Berlin undertook investigations into polio-myelitis immunity in 1972. A total of 267 persons aged up to 20 years were investigated for neutralizing antibodies against the three types of polio virus. The study showed that from the fourth year of life approximately 70% of the persons investigated had antibodies against all three types of polio virus. In some younger children the equivalent values were considerably lower. After the fourth year of life there were only slight differences in the humoral immunity against the three polio virus types. There was no evidence that the immunity level had deteriorated up to the 20th year of life and thus there is no indication of the necessity for a repeat immunisation at a certain time. The investigation confirmed that three oral administrations of trivalent vaccine, as are now generally recommended as basic immunization in the German Federal Republic, result in a conversion rate of over 90% against each of the three virus types."} {"id": "PMID:163179", "title": "[Endocrinological and histomorphological studies of testicular atrophy in myotonic dystrophy (author's transl)].", "content": "Testicular atrophy in myotonic dystrophy is caused by a primary and progressive atrophy of the seminiferous tubules. Endocrinological studies with synthetic LH(ICSH)-RH in two patients demonstrated the complete absence of FSH feed back mechanism. Glycogen content was markedly diminished or completely absent, as demonstrated histochemically, both in the morphologically intact and in damaged tubules. The endocrinological and morphological results both demonstrate that insufficiency of the Sertoli cells is the primary damage in the pathogenesis of testicular atrophy in myotonic dystrophy.", "contents": "[Endocrinological and histomorphological studies of testicular atrophy in myotonic dystrophy (author's transl)]. Testicular atrophy in myotonic dystrophy is caused by a primary and progressive atrophy of the seminiferous tubules. Endocrinological studies with synthetic LH(ICSH)-RH in two patients demonstrated the complete absence of FSH feed back mechanism. Glycogen content was markedly diminished or completely absent, as demonstrated histochemically, both in the morphologically intact and in damaged tubules. The endocrinological and morphological results both demonstrate that insufficiency of the Sertoli cells is the primary damage in the pathogenesis of testicular atrophy in myotonic dystrophy."} {"id": "PMID:163181", "title": "Synthesis and inducibility of the Uterine estrogen-induced protein, IP, during the rat estrous cycle: clues to uterine estrogen sensitivity.", "content": "Analysis of newly labeled soluble proteins in uteri of mature rats throughout the estrous cycle indicates that the relative rate of synthesis of the uterine estrogen-induced protein, IP, is high at proestrus, when endogenous estrogen secretion is maximal; it is not synthesized at detectable levels at estrus and metestrus; and some minimal synthesis is seen in diestrus uteri. Injection of exogenous estrogen results in some increase in the IP synthesis rate at proestrus; slight induction of IP synthesis at estrus; and maximal induction (as great as that induced in the mature, ovariectomized uterus by estrogen) at metestrus and diestrus. Studies in the immature (day 21-24) rat, aimed at determining the possible causes of the uterine recalcitrance to exogenous estrogen seen at estrus, indicate that one can reproduce in the immature uterus a period of feeble responsiveness to a second injection of estrogen after exposure to a first, high dose of estrogen. After a single injection of estrogen, there is a lag between the gradual return of full IP inducibility (requiring over 40 hours to reach the control level) and the return of nuclear-translocatable receptor (at control level by 24 hr). This suggests that in addition to the presence of nuclear-translocatable receptor, the response to a second injection of estrogen is dependent upon other factors whose replenishment and/or reactivation is slower than that of the receptor.", "contents": "Synthesis and inducibility of the Uterine estrogen-induced protein, IP, during the rat estrous cycle: clues to uterine estrogen sensitivity. Analysis of newly labeled soluble proteins in uteri of mature rats throughout the estrous cycle indicates that the relative rate of synthesis of the uterine estrogen-induced protein, IP, is high at proestrus, when endogenous estrogen secretion is maximal; it is not synthesized at detectable levels at estrus and metestrus; and some minimal synthesis is seen in diestrus uteri. Injection of exogenous estrogen results in some increase in the IP synthesis rate at proestrus; slight induction of IP synthesis at estrus; and maximal induction (as great as that induced in the mature, ovariectomized uterus by estrogen) at metestrus and diestrus. Studies in the immature (day 21-24) rat, aimed at determining the possible causes of the uterine recalcitrance to exogenous estrogen seen at estrus, indicate that one can reproduce in the immature uterus a period of feeble responsiveness to a second injection of estrogen after exposure to a first, high dose of estrogen. After a single injection of estrogen, there is a lag between the gradual return of full IP inducibility (requiring over 40 hours to reach the control level) and the return of nuclear-translocatable receptor (at control level by 24 hr). This suggests that in addition to the presence of nuclear-translocatable receptor, the response to a second injection of estrogen is dependent upon other factors whose replenishment and/or reactivation is slower than that of the receptor."} {"id": "PMID:163182", "title": "Hormonal influences on the level of testicular androgen binding activity: effect of FSH following hypophysectomy.", "content": "Concentrations of high affinity (Ka equals 5.5 plus or minus 0.83 times 10-8M-1) androgen binding activity in carbonextracted rat testicular supernatants have been determined by Scatchard plot analysis under a variety of hormonal situations: (a) 0-90 days following hypophysectomy; (b) 0-60 days of daily injection of NIH-FSH-P1 (150 mug) beginning 1 day after hypophysectomy; and (c) 0-60 days of daily FSH treatment beginning 30 days after hypophysectomy. The high affinity binding component declined from 0.32 pmoles/mg protein intact adults to 0.28, 0.17, and less than 0.08 (limit of detectability) pmoles/mg protein at 11, 16 and 31 days, respectively. FSH treatment beginning immediately after surgery slowed this decline, giving values of 0.30, 0.17, and 0.12 pmoles/mg protein after 11, 29, and 54 days of treatment, respectively. Expressed as pmoles per testis this represented 96, 61, and 40% of the intact control level. Similar effects on the level of androgen binding protein (Rf 0.54) were measured by steady-state polyacrylamide gel electrophoresis (PAGE). The concentration in both testis and epididymis declined gradually to nondetectable levels by 30 days after surgery. FSH treatment for 11, 29, and 54 days, respectively, resulted in 0.37, 0.38, and 0.03 pmoles of sites/mg protein in testis compared to 0.34 in intact controls and 5.7, 2.6, and 0.2 pmoles/mg protein in epididymis compared to 2.8 in intact controls. Doses of 80, 150, and 300 mug FSH/rat/day for 3 days beginning 30 days after hypophysectomy when postmeiotic elements of the germinal epithelium had degenerated caused graded increases in both testicular and epididymal levels of androgen binding protein. Prolonged FSH treatment (150 mug) under these conditions resulted in an increase in binding activity to a level of 0.12, 0.19, 0.17, and 0.20 pmoles/mg protein after 3, 11, 25, and 56 days of treatment. On a per testis basis this represented less than 20% of intact control levels. PAGE estimates were comparable except at the long treatment intervals. These results indicate that FSH treatment influences the level of androgen binding protein in adult testis and epididymis. This may reflect a direct influence on synthesis, degradation, and transport and/or indirect effects on general maintenance and responsiveness of the pertinent cell types.", "contents": "Hormonal influences on the level of testicular androgen binding activity: effect of FSH following hypophysectomy. Concentrations of high affinity (Ka equals 5.5 plus or minus 0.83 times 10-8M-1) androgen binding activity in carbonextracted rat testicular supernatants have been determined by Scatchard plot analysis under a variety of hormonal situations: (a) 0-90 days following hypophysectomy; (b) 0-60 days of daily injection of NIH-FSH-P1 (150 mug) beginning 1 day after hypophysectomy; and (c) 0-60 days of daily FSH treatment beginning 30 days after hypophysectomy. The high affinity binding component declined from 0.32 pmoles/mg protein intact adults to 0.28, 0.17, and less than 0.08 (limit of detectability) pmoles/mg protein at 11, 16 and 31 days, respectively. FSH treatment beginning immediately after surgery slowed this decline, giving values of 0.30, 0.17, and 0.12 pmoles/mg protein after 11, 29, and 54 days of treatment, respectively. Expressed as pmoles per testis this represented 96, 61, and 40% of the intact control level. Similar effects on the level of androgen binding protein (Rf 0.54) were measured by steady-state polyacrylamide gel electrophoresis (PAGE). The concentration in both testis and epididymis declined gradually to nondetectable levels by 30 days after surgery. FSH treatment for 11, 29, and 54 days, respectively, resulted in 0.37, 0.38, and 0.03 pmoles of sites/mg protein in testis compared to 0.34 in intact controls and 5.7, 2.6, and 0.2 pmoles/mg protein in epididymis compared to 2.8 in intact controls. Doses of 80, 150, and 300 mug FSH/rat/day for 3 days beginning 30 days after hypophysectomy when postmeiotic elements of the germinal epithelium had degenerated caused graded increases in both testicular and epididymal levels of androgen binding protein. Prolonged FSH treatment (150 mug) under these conditions resulted in an increase in binding activity to a level of 0.12, 0.19, 0.17, and 0.20 pmoles/mg protein after 3, 11, 25, and 56 days of treatment. On a per testis basis this represented less than 20% of intact control levels. PAGE estimates were comparable except at the long treatment intervals. These results indicate that FSH treatment influences the level of androgen binding protein in adult testis and epididymis. This may reflect a direct influence on synthesis, degradation, and transport and/or indirect effects on general maintenance and responsiveness of the pertinent cell types."} {"id": "PMID:163183", "title": "The role of prolactin in the luteotrophic process of lactating rats.", "content": "Treatment of pseudopregnant rats with ergocryptine mesylate (ECR) depressed serum prolactin levels but had no apparent effect on LH secretion. Ovarian progesterone secretion was significantly, reduced 24 hr after ECR treatment on day 6 or 9 of pseudopregnancy and the secretion rate of 20alpha-OH-P remained constant. When lactating rats nursing 6 pups were treated with ECR on day 6 or 9 postpartum, progesterone secretion was significantly decreased by 48 hr after treatment and 20 alpha-OH-P secretion was not altered. Furthermore, ECR inhibited litter weight gains of these lactating dams. After treatment of normal pregnant and pregnant lactating rats with ECR on day 6 of pregnancy, gestation was terminated in all animals. If ECR was given on day 9 to normal pregnant rats, to pregnant lactating animals whose pups were removed on day 9 postpartum, or to pregnant lactating rats treated with LH, gestation was not terminated. However, treatment with ECR of day 9 pregnant lactating rats whose pups continued to suckle terminated pregnancy in 13 of 21 animals. The results of these studies suggest the elevated pituitary prolactin secretion is necessary for maintenance of luteal function in pseudopregnant and lactating rats, and in pregnant lactating rats elevated pituitary prolactin secretion is a component of the luteotrophic complex for a longer period of time than in normal pregnant rats.", "contents": "The role of prolactin in the luteotrophic process of lactating rats. Treatment of pseudopregnant rats with ergocryptine mesylate (ECR) depressed serum prolactin levels but had no apparent effect on LH secretion. Ovarian progesterone secretion was significantly, reduced 24 hr after ECR treatment on day 6 or 9 of pseudopregnancy and the secretion rate of 20alpha-OH-P remained constant. When lactating rats nursing 6 pups were treated with ECR on day 6 or 9 postpartum, progesterone secretion was significantly decreased by 48 hr after treatment and 20 alpha-OH-P secretion was not altered. Furthermore, ECR inhibited litter weight gains of these lactating dams. After treatment of normal pregnant and pregnant lactating rats with ECR on day 6 of pregnancy, gestation was terminated in all animals. If ECR was given on day 9 to normal pregnant rats, to pregnant lactating animals whose pups were removed on day 9 postpartum, or to pregnant lactating rats treated with LH, gestation was not terminated. However, treatment with ECR of day 9 pregnant lactating rats whose pups continued to suckle terminated pregnancy in 13 of 21 animals. The results of these studies suggest the elevated pituitary prolactin secretion is necessary for maintenance of luteal function in pseudopregnant and lactating rats, and in pregnant lactating rats elevated pituitary prolactin secretion is a component of the luteotrophic complex for a longer period of time than in normal pregnant rats."} {"id": "PMID:163184", "title": "Triiodothyronine binding to isolated liver cell nuclei.", "content": "Nuclei of euthyroid rat liver have been prepared from homogenates by sedimentation through 2.3M sucrose with or without a 0.25% Triton wash. Triiodothyronine is accumulated by these nuclei during incubation in vitro in solutions containing 0.32M sucrose, 1mM MgCl2 and 0.02M Tris-Cl buffer at pH 7.4 or 7.85. Specific T3 binding sites occupied at 10-1,000 pM T3 are saturated by excess unlabeled T3 (0.15 muM). Specific T3 binding at 20 C is maximal at 203 hr nad is proportional to amount of nuclei. Calcium ion enhances nuclear integrity by reduces T3 accumulation. EDTA and phosphate ion cause nuclear damage but increase T3 accumulation. Binding is unaffected by inhibition of energy dependent reactions or of RNA synthesis. It is markedly increased under certain conditions by addition of dithiothreitol (DDT). Binding does not require mediation of a cytosol protein. T3 binding is not prevented by RNAse or DNAse, but is obliterated by pronase. Te binds to a nuclear iodothyronine binding protein (NTBP) to form an NTBP-T3 complex similar to that form-d after in vivo administration of the hormone. The complex can be extracted from the nuclei by 0.4M KC-. T3 present in the NTBP-T3 complex resists accumulation by anion exchange resin at 0-2C, but is bound by resin after 20 min at 37C or after addition of 0.1 mM p-hydroxymercuribenzoate. At pH 7.85 and with 5 mM DTT, the apparent Ka for isolated nuclei is 0.2 times 10-10M-1 and the capacity is 508 pg T3/g wet tissue or 53 times 10-15 moles T3/100 mug DNA. The data may not represent total capacity, but rather the amount of T3 dissociated during the period of incubation so that NTBP-T3 can be exchanged with labeled T3. Among analogues tested, triiodothyroacetic acid appears to bind with four times the affinity of L-TX, D-T3 binds with equal affinity, and L-T4 with one-fourth the affinity of T3.", "contents": "Triiodothyronine binding to isolated liver cell nuclei. Nuclei of euthyroid rat liver have been prepared from homogenates by sedimentation through 2.3M sucrose with or without a 0.25% Triton wash. Triiodothyronine is accumulated by these nuclei during incubation in vitro in solutions containing 0.32M sucrose, 1mM MgCl2 and 0.02M Tris-Cl buffer at pH 7.4 or 7.85. Specific T3 binding sites occupied at 10-1,000 pM T3 are saturated by excess unlabeled T3 (0.15 muM). Specific T3 binding at 20 C is maximal at 203 hr nad is proportional to amount of nuclei. Calcium ion enhances nuclear integrity by reduces T3 accumulation. EDTA and phosphate ion cause nuclear damage but increase T3 accumulation. Binding is unaffected by inhibition of energy dependent reactions or of RNA synthesis. It is markedly increased under certain conditions by addition of dithiothreitol (DDT). Binding does not require mediation of a cytosol protein. T3 binding is not prevented by RNAse or DNAse, but is obliterated by pronase. Te binds to a nuclear iodothyronine binding protein (NTBP) to form an NTBP-T3 complex similar to that form-d after in vivo administration of the hormone. The complex can be extracted from the nuclei by 0.4M KC-. T3 present in the NTBP-T3 complex resists accumulation by anion exchange resin at 0-2C, but is bound by resin after 20 min at 37C or after addition of 0.1 mM p-hydroxymercuribenzoate. At pH 7.85 and with 5 mM DTT, the apparent Ka for isolated nuclei is 0.2 times 10-10M-1 and the capacity is 508 pg T3/g wet tissue or 53 times 10-15 moles T3/100 mug DNA. The data may not represent total capacity, but rather the amount of T3 dissociated during the period of incubation so that NTBP-T3 can be exchanged with labeled T3. Among analogues tested, triiodothyroacetic acid appears to bind with four times the affinity of L-TX, D-T3 binds with equal affinity, and L-T4 with one-fourth the affinity of T3."} {"id": "PMID:163185", "title": "Progestational function of perifused rat corpora lutea.", "content": "Corpora lutea (CL) from synchronously ovulated, prepubertal rats remained viable in perifusing Eagle medium (Dulbecco modified) flowing at a rate of 1 ml/hr. As an index of viability, progesterone (P) and 20alpha-hydroxypreng-4-ene-3-one (20alpha-OH-P) were determined by radioimmunoa-say in effluent media. Corpora lutea removed on the 2nd day of diestrus (D-2) or the 2nd day of pseudopregnancy (PP-2) showed fatigue by a continuous decline in the concentrations of effluent progestins. P decreased from 2 to 0.2 ng/ml/CL during an interval of 5 hr, while 20alpha-OH-P decreased from 2.2 to about 0.7 ng/ml/CL. In contrast corpora lutea taken on PP-4 maintained higher progestin levels in the effluent media. P present initially at 2.2 ng/ml/CL decreased to 0.73 ng/ml/CL; 20alpha-OH-P, initial concentration 0.84 ng/ml/CL, decreased to 0.41 ng/ml/CL. The greater functionality of PP-4 CL indicated by the continued predominance of , suggested an in vivo imposition of a luteotropic stimulus occurring after PP-2. Addition of bovine LH (NIH-LH-B8, 20 mug/ml) to the perifusing medium stimulated steroidogenesis by PP-2 CL during which 20alpha-OH-P levels remained between 2.3 and 3.2 ng/ml/CL throughout perifusion, while P secretion decreased from 2.9 to 0.9 ng/ml/CL. Prolactin (NIH-P-B3, 20 mug/ml), did not significantly alter the original secretion pattern of PP-2 CL. During combined prolactin (20 mug/ml) and LH (2 to 10 mug/ml) perifusion, P secretion predominated, decreasing from 3.9 to 1.0 ng/ml/CL; 20alpha-OH-P decreased from 1.2 to 0.7 ng/ml/CL.", "contents": "Progestational function of perifused rat corpora lutea. Corpora lutea (CL) from synchronously ovulated, prepubertal rats remained viable in perifusing Eagle medium (Dulbecco modified) flowing at a rate of 1 ml/hr. As an index of viability, progesterone (P) and 20alpha-hydroxypreng-4-ene-3-one (20alpha-OH-P) were determined by radioimmunoa-say in effluent media. Corpora lutea removed on the 2nd day of diestrus (D-2) or the 2nd day of pseudopregnancy (PP-2) showed fatigue by a continuous decline in the concentrations of effluent progestins. P decreased from 2 to 0.2 ng/ml/CL during an interval of 5 hr, while 20alpha-OH-P decreased from 2.2 to about 0.7 ng/ml/CL. In contrast corpora lutea taken on PP-4 maintained higher progestin levels in the effluent media. P present initially at 2.2 ng/ml/CL decreased to 0.73 ng/ml/CL; 20alpha-OH-P, initial concentration 0.84 ng/ml/CL, decreased to 0.41 ng/ml/CL. The greater functionality of PP-4 CL indicated by the continued predominance of , suggested an in vivo imposition of a luteotropic stimulus occurring after PP-2. Addition of bovine LH (NIH-LH-B8, 20 mug/ml) to the perifusing medium stimulated steroidogenesis by PP-2 CL during which 20alpha-OH-P levels remained between 2.3 and 3.2 ng/ml/CL throughout perifusion, while P secretion decreased from 2.9 to 0.9 ng/ml/CL. Prolactin (NIH-P-B3, 20 mug/ml), did not significantly alter the original secretion pattern of PP-2 CL. During combined prolactin (20 mug/ml) and LH (2 to 10 mug/ml) perifusion, P secretion predominated, decreasing from 3.9 to 1.0 ng/ml/CL; 20alpha-OH-P decreased from 1.2 to 0.7 ng/ml/CL."} {"id": "PMID:163186", "title": "Effect of luteinizing hormone and cyclic adenosine 3',5'-monophosphate on steroidogenesis in the ovarian follicle of the rabbit.", "content": "Mature ovarian follicles have been isolated from estrus rabbits and the effects of gonadotropin and cyclic AMP on steroidogenesis in this tissue determined. Gonadotropins used include LH, FSH, and prolactin; follicular levels of progesterone, 17-hydroxyprogesterone, testosterone and 17beta-estradiol in all experiments were quantitated by radioimmunoassay. Incubation of follicles with LH in concentrations ranging from 0.05 to 50 mug/ml medium yielded increases in the total ng steroid/follicle. Five mug LH/ml gave a maximal response with no further increase in steroid concentration when the LH was raised to 50 mug/ml. Prolactin had no effect on follicular steroidogenesis while the stimulatory action of a FSH preparation could only be partially attributed to LH contamination. Cyclic AMP also proved to be a potent stimulatory agent in follicular steroidogenesis with maximal increases at 20 mumoles/ml and a decline in the ng steroid/follicle when cyclic AMP was raised to 30 and 40 mumoles/ml. The effects of LH and cyclic AMP proved to be nonadditive; incubation of follicles simultaneously with 5 mug LH/ml and 20 mumoles cyclic AMP/ml yielded steroid concentrations which were no different than levels following incubation with either agent alone. Taken together, these results demonstrate that both LH and cyclic AMP cause increases in radioimmunoassayable steroid in the rabbit follicle in vitro and that LH probably acts by way of a cyclic AMP intermediate.", "contents": "Effect of luteinizing hormone and cyclic adenosine 3',5'-monophosphate on steroidogenesis in the ovarian follicle of the rabbit. Mature ovarian follicles have been isolated from estrus rabbits and the effects of gonadotropin and cyclic AMP on steroidogenesis in this tissue determined. Gonadotropins used include LH, FSH, and prolactin; follicular levels of progesterone, 17-hydroxyprogesterone, testosterone and 17beta-estradiol in all experiments were quantitated by radioimmunoassay. Incubation of follicles with LH in concentrations ranging from 0.05 to 50 mug/ml medium yielded increases in the total ng steroid/follicle. Five mug LH/ml gave a maximal response with no further increase in steroid concentration when the LH was raised to 50 mug/ml. Prolactin had no effect on follicular steroidogenesis while the stimulatory action of a FSH preparation could only be partially attributed to LH contamination. Cyclic AMP also proved to be a potent stimulatory agent in follicular steroidogenesis with maximal increases at 20 mumoles/ml and a decline in the ng steroid/follicle when cyclic AMP was raised to 30 and 40 mumoles/ml. The effects of LH and cyclic AMP proved to be nonadditive; incubation of follicles simultaneously with 5 mug LH/ml and 20 mumoles cyclic AMP/ml yielded steroid concentrations which were no different than levels following incubation with either agent alone. Taken together, these results demonstrate that both LH and cyclic AMP cause increases in radioimmunoassayable steroid in the rabbit follicle in vitro and that LH probably acts by way of a cyclic AMP intermediate."} {"id": "PMID:163187", "title": "The morphological transformation and inhibition of growth of bovine luteal cells in tissue culture induced by luteinizing hormone and dibutyryl cyclic AMP.", "content": "The luteal cells obtained from bovine corpus luteum by enzymatic treatment have been maintained in tissue culture. When the cells were maintained in the absence of luteinizing hormone or dibutyryl cyclic AMP, they grew parallel to one another and were elongated, thus giving to the culture a fibroblastic appearance. No contact inhibition was observed and the progestin secretion rate was low (3 pg per cell per day). In contrast, when luteinizing hormone or dibutyryl cyclic AMP was present, the cells became polygonal, growing as a monolayer and taking the appearance of epithelial cells. In this case contact inhibition was observed. The rate of progestin secretion was 250 pg per cell per day. As soon as luteinizing hormone or dibutyryl cyclic AMP was removed from the media, the cells reverted to a fibroblastic appearance. Agents such as colcemid, vinblastin or cytochalasin B inhibited the morphological effect of luteinizing hormone or dibutyryl cyclic AMP. Since those agents are known to inhibit the assembly of microtubules, the data suggest that LH and dibutyryl cyclic AMP act by promoting the organization of microtubules from protein monomers. This microtubular system (cytoskeleton) is responsible for the morphological appearance of the cells. Concomitant with the morphological changes induced by luteinizing hormone and dibutyryl cyclic AMP an inhibition in the growth rate of luteal cells was observed. It suggests that by raising the intracellular level of cyclic AMP the luteinizing hormone inhibits the division of luteal cells and is not, for that reason, a mitogenic agent. A similar effect was obtained with other agents known to stimulate cyclic AMP production such asthe prostaglandins. Steroids such as glucocorticoids and testosterone but not progesterone also inhibited the growth rate. It is concluded that luteinizing hormone by controlling the level of cyclic AMP within the luteal cells is responsible for the expression of the phenotype of the cells and the maintenance of differentiation.", "contents": "The morphological transformation and inhibition of growth of bovine luteal cells in tissue culture induced by luteinizing hormone and dibutyryl cyclic AMP. The luteal cells obtained from bovine corpus luteum by enzymatic treatment have been maintained in tissue culture. When the cells were maintained in the absence of luteinizing hormone or dibutyryl cyclic AMP, they grew parallel to one another and were elongated, thus giving to the culture a fibroblastic appearance. No contact inhibition was observed and the progestin secretion rate was low (3 pg per cell per day). In contrast, when luteinizing hormone or dibutyryl cyclic AMP was present, the cells became polygonal, growing as a monolayer and taking the appearance of epithelial cells. In this case contact inhibition was observed. The rate of progestin secretion was 250 pg per cell per day. As soon as luteinizing hormone or dibutyryl cyclic AMP was removed from the media, the cells reverted to a fibroblastic appearance. Agents such as colcemid, vinblastin or cytochalasin B inhibited the morphological effect of luteinizing hormone or dibutyryl cyclic AMP. Since those agents are known to inhibit the assembly of microtubules, the data suggest that LH and dibutyryl cyclic AMP act by promoting the organization of microtubules from protein monomers. This microtubular system (cytoskeleton) is responsible for the morphological appearance of the cells. Concomitant with the morphological changes induced by luteinizing hormone and dibutyryl cyclic AMP an inhibition in the growth rate of luteal cells was observed. It suggests that by raising the intracellular level of cyclic AMP the luteinizing hormone inhibits the division of luteal cells and is not, for that reason, a mitogenic agent. A similar effect was obtained with other agents known to stimulate cyclic AMP production such asthe prostaglandins. Steroids such as glucocorticoids and testosterone but not progesterone also inhibited the growth rate. It is concluded that luteinizing hormone by controlling the level of cyclic AMP within the luteal cells is responsible for the expression of the phenotype of the cells and the maintenance of differentiation."} {"id": "PMID:163188", "title": "The intranuclear binding of 17 beta-hydroxy-5 alpha-androstan-3-one and testosterone by hamster sebaceous glands.", "content": "After the administration of 3-H-testosterone to castrated hamsters, extracts from crude nuclei were separated into bound and free fractions by gel filtration of Sephadex G-25, Subsequent analysis by thin-layer chromatography and recrystallization showed that dihydrotestosterone was the predominant radioactive steroid in the bound fraction and that it increased steadily with time until 1 hr after the injection. Further purification of the nuclear fraction showed an abundance of dihydrotestosterone in the nuclei. The binding was significantly decreased by pronase treatment, only slightly affected by deoxyribonuclease, and remained unaffected by ribonuclease. From the elution pattern on Sephadex G-200, the molecular weight of the binding macromolecule was estimated to be 3 times 10-4 daltons.", "contents": "The intranuclear binding of 17 beta-hydroxy-5 alpha-androstan-3-one and testosterone by hamster sebaceous glands. After the administration of 3-H-testosterone to castrated hamsters, extracts from crude nuclei were separated into bound and free fractions by gel filtration of Sephadex G-25, Subsequent analysis by thin-layer chromatography and recrystallization showed that dihydrotestosterone was the predominant radioactive steroid in the bound fraction and that it increased steadily with time until 1 hr after the injection. Further purification of the nuclear fraction showed an abundance of dihydrotestosterone in the nuclei. The binding was significantly decreased by pronase treatment, only slightly affected by deoxyribonuclease, and remained unaffected by ribonuclease. From the elution pattern on Sephadex G-200, the molecular weight of the binding macromolecule was estimated to be 3 times 10-4 daltons."} {"id": "PMID:163189", "title": "Diguanosinetetraphosphatase from rat liver: Acitivity on diadenosine tetraphosphate and inhibition by adenosine tetraphosphate.", "content": "The hydrolysis of diadenosine tetraphosphate, a compound previously described by others to occur in liver at concentrations of around 0.1 mu M, is carried out by a specific enzyme. This enzyme has been partially purified from rat liver extracts, and the following properties have been found. The Km value for diadenosine tetraphosphate is 2 mu M; the products of hydrolysis are ATP and AMP; the Km value for diguanosine tetraphosphate is 2 mu M; none of the following substances were substrates of the enzyme: diadenosine triphosphate, diguanosine di and triphosphates, adenosine tetraphosphate, ATP, ADP, NAD+, NADP+ and bis-p-nitrophenylphosphate. Cyclic AMP was not an inhibitor of the reaction. The enzyme requires Mg2+ ions, is maximally active at a pH value of approximately 8, and has a molecular weight of 22000 as estimated by filtration on Sephadex G-100. The activation energy of the reaction was of 10250 cal times mol-1 (42886 J times mol-1). Particularly striking is the inhibition by adenosine tetraphosphate (Ki equals 48 nM) and guanosine tetraphosphate (Ki equals 14 nM). Other nucleotides tested were also competitive inhibitors with Ki values in the 10--100 mu M range.", "contents": "Diguanosinetetraphosphatase from rat liver: Acitivity on diadenosine tetraphosphate and inhibition by adenosine tetraphosphate. The hydrolysis of diadenosine tetraphosphate, a compound previously described by others to occur in liver at concentrations of around 0.1 mu M, is carried out by a specific enzyme. This enzyme has been partially purified from rat liver extracts, and the following properties have been found. The Km value for diadenosine tetraphosphate is 2 mu M; the products of hydrolysis are ATP and AMP; the Km value for diguanosine tetraphosphate is 2 mu M; none of the following substances were substrates of the enzyme: diadenosine triphosphate, diguanosine di and triphosphates, adenosine tetraphosphate, ATP, ADP, NAD+, NADP+ and bis-p-nitrophenylphosphate. Cyclic AMP was not an inhibitor of the reaction. The enzyme requires Mg2+ ions, is maximally active at a pH value of approximately 8, and has a molecular weight of 22000 as estimated by filtration on Sephadex G-100. The activation energy of the reaction was of 10250 cal times mol-1 (42886 J times mol-1). Particularly striking is the inhibition by adenosine tetraphosphate (Ki equals 48 nM) and guanosine tetraphosphate (Ki equals 14 nM). Other nucleotides tested were also competitive inhibitors with Ki values in the 10--100 mu M range."} {"id": "PMID:163190", "title": "Purification of bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and phosphoglyceromutase from human erthrocytes. Three enzyme activities in one protein.", "content": "Bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and phosphoglyceromutase have been purified from human red cells. Three enzymes were co-purified throughout all purification steps. Three fractions (peaks I, II and III) which were chromatographically separable and had three activities in different ratios were obtained. Peak III which contained the main bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities was purified to homogeneity by electrophoretic and ultracentrifugal analyses. The homogeneous preparation had the phosphoglyceromutase activity. The three activities were lost at the same rate during thermal inactivation. Thus, bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities, which are responsible for 2,3-bisphosphoglycerate metabolism in red cells, are displayed by the same enzyme protein which has phosphoglyceromutase activity. Peaks I and II were rich in the phosphoglyceromutase activity. Both peaks showed bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities, although these two activities were much smaller than those of peak III. Some of the enzymic properties of peak III are described. Comparative studies on three peaks showed that the phosphoglyceromutase of peak III differed from that of peaks I and II in the kinetic property and thermostability.", "contents": "Purification of bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and phosphoglyceromutase from human erthrocytes. Three enzyme activities in one protein. Bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and phosphoglyceromutase have been purified from human red cells. Three enzymes were co-purified throughout all purification steps. Three fractions (peaks I, II and III) which were chromatographically separable and had three activities in different ratios were obtained. Peak III which contained the main bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities was purified to homogeneity by electrophoretic and ultracentrifugal analyses. The homogeneous preparation had the phosphoglyceromutase activity. The three activities were lost at the same rate during thermal inactivation. Thus, bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities, which are responsible for 2,3-bisphosphoglycerate metabolism in red cells, are displayed by the same enzyme protein which has phosphoglyceromutase activity. Peaks I and II were rich in the phosphoglyceromutase activity. Both peaks showed bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities, although these two activities were much smaller than those of peak III. Some of the enzymic properties of peak III are described. Comparative studies on three peaks showed that the phosphoglyceromutase of peak III differed from that of peaks I and II in the kinetic property and thermostability."} {"id": "PMID:163217", "title": "Effect of local infection and oral contraception on immunoglobulin levels in cervical mucus.", "content": "The concentrations of immunoglobulin A (IgA) and immunoglobulin G (IgG) were estimated in cervical mucus from 115 patients attending a clinic for sexually transmitted diseases. The patients were divided into two groups; those using combined estrogen/progestogen oral contraceptives, and those with presumed normal ovulatory cycles. Gonorrhea, trichomoniasis, candidosis, and herpes genitalis were diagnosed by conventional smear and culture techniques, and the two groups were subdivided according to these diagnoses. Gonorrhea, trichomoniasis, herpetic, and nonspecific cervicitis all caused marked increases in the mean concentrations when compared with a control group of uninfected patients with natural cycles (P = less than 0.01). Patients with candidosis and contacts of men with nonspecific urethritis showed a lesser rise. IgG/IgA ratios lower than that of serum suggested a considerable locally produced contribution of IgA. Oral contraception with the combined pill also caused a significant increase in mean IgA and IgG levels even in the absence of local infection (P = less than 0.01). an increase in the IgG/IgA ratio of this group may indicate that the hormonal effect was manifest through increased serum transudation. IgM was also detected more commonly in patients taking the pill. The marked effect of local disease on immunoglobulin levels in cervical mucus which occurs even in asymptomatic patients emphasizes the importance of screening for infection when studying these secretions.", "contents": "Effect of local infection and oral contraception on immunoglobulin levels in cervical mucus. The concentrations of immunoglobulin A (IgA) and immunoglobulin G (IgG) were estimated in cervical mucus from 115 patients attending a clinic for sexually transmitted diseases. The patients were divided into two groups; those using combined estrogen/progestogen oral contraceptives, and those with presumed normal ovulatory cycles. Gonorrhea, trichomoniasis, candidosis, and herpes genitalis were diagnosed by conventional smear and culture techniques, and the two groups were subdivided according to these diagnoses. Gonorrhea, trichomoniasis, herpetic, and nonspecific cervicitis all caused marked increases in the mean concentrations when compared with a control group of uninfected patients with natural cycles (P = less than 0.01). Patients with candidosis and contacts of men with nonspecific urethritis showed a lesser rise. IgG/IgA ratios lower than that of serum suggested a considerable locally produced contribution of IgA. Oral contraception with the combined pill also caused a significant increase in mean IgA and IgG levels even in the absence of local infection (P = less than 0.01). an increase in the IgG/IgA ratio of this group may indicate that the hormonal effect was manifest through increased serum transudation. IgM was also detected more commonly in patients taking the pill. The marked effect of local disease on immunoglobulin levels in cervical mucus which occurs even in asymptomatic patients emphasizes the importance of screening for infection when studying these secretions."} {"id": "PMID:163218", "title": "Antigenic response to topically applied proteins.", "content": "Six different proteins varying widely in molecular weight, ribonuclease, lysostaphin, ovalbumin, penicillinase, collagenase, and Varidase were tested for their ability to induce circulating antibody formation in rabbits after repeated topical application of the proteins in a water-soluble gel vehicle. After a 12-week exposure period, significant hemagglutinin titers were noted in rabbits treated with ovalbumin, lysostaphin, or ribonuclease; markedly elevated, passive cutaneous anaphylaxis-reacting sera were obtained only from collagenase- or lysostaphin-treated animals. Precipitin antibodies as evidenced by gel diffusion were also found in sera from collagenas- and lysostaphin-treated animals. Topical application of penicillinase was only marginally effective and Varidase was totally ineffective in elicting a positive circulating antibody response. In all cases, topical application of proteins for periods in excess of 3 weeks was required for induction of circulating antibody formation.", "contents": "Antigenic response to topically applied proteins. Six different proteins varying widely in molecular weight, ribonuclease, lysostaphin, ovalbumin, penicillinase, collagenase, and Varidase were tested for their ability to induce circulating antibody formation in rabbits after repeated topical application of the proteins in a water-soluble gel vehicle. After a 12-week exposure period, significant hemagglutinin titers were noted in rabbits treated with ovalbumin, lysostaphin, or ribonuclease; markedly elevated, passive cutaneous anaphylaxis-reacting sera were obtained only from collagenase- or lysostaphin-treated animals. Precipitin antibodies as evidenced by gel diffusion were also found in sera from collagenas- and lysostaphin-treated animals. Topical application of penicillinase was only marginally effective and Varidase was totally ineffective in elicting a positive circulating antibody response. In all cases, topical application of proteins for periods in excess of 3 weeks was required for induction of circulating antibody formation."} {"id": "PMID:163219", "title": "Adenosine 3',5'-cyclic monophosphate in Vibrio cholerae.", "content": "The extracellular concentration of cyclic adenosine 3',5'-monophosphate (AMP) of three different strains of Vibrio cholerae growing in syncase medium were measured. Cyclic AMP secreted by V. cholerae 569B varied widely, with different carbon sources. Mutant 13, which produced little or no toxin, released half the amount of cyclic AMP as the wild type. The release of less cyclic AMP into the medium by mutant 13 may be accounted for by the lower activity of adenylate cyclase observed. High glucose (3%) in the culture medium reduced the concentration of cyclic AMP both in wild type and mutant 13. Reduction of cyclic AMP levels at high concentrations of glucose (3%) occurred without change of adenylate cyclase activity. The release of enterotoxin to the medium varied with carbon sources but was independent of conditions which reduced the cyclic AMP both within the cell and the medium. Neither adenylate cyclase activity nor toxin production was reduced by an increase concentration of glucose in wild-type V. cholerae, whereas cyclic AMP levels were reduced by sixfold. A lower activity of the adenylate cyclase was observed in a mutant of V. cholerae which produced no detectable toxin. Thus, a correlation exists between toxin production and adenylate cyclase activity in V. cholerae.", "contents": "Adenosine 3',5'-cyclic monophosphate in Vibrio cholerae. The extracellular concentration of cyclic adenosine 3',5'-monophosphate (AMP) of three different strains of Vibrio cholerae growing in syncase medium were measured. Cyclic AMP secreted by V. cholerae 569B varied widely, with different carbon sources. Mutant 13, which produced little or no toxin, released half the amount of cyclic AMP as the wild type. The release of less cyclic AMP into the medium by mutant 13 may be accounted for by the lower activity of adenylate cyclase observed. High glucose (3%) in the culture medium reduced the concentration of cyclic AMP both in wild type and mutant 13. Reduction of cyclic AMP levels at high concentrations of glucose (3%) occurred without change of adenylate cyclase activity. The release of enterotoxin to the medium varied with carbon sources but was independent of conditions which reduced the cyclic AMP both within the cell and the medium. Neither adenylate cyclase activity nor toxin production was reduced by an increase concentration of glucose in wild-type V. cholerae, whereas cyclic AMP levels were reduced by sixfold. A lower activity of the adenylate cyclase was observed in a mutant of V. cholerae which produced no detectable toxin. Thus, a correlation exists between toxin production and adenylate cyclase activity in V. cholerae."} {"id": "PMID:163220", "title": "Cell-mediated immunity to Herpes simplex in humans: lymphocyte cytotoxicity measured by 51-Cr release from infected cells.", "content": "We assessed cell-mediated immunity to herpes simplex virus type 1 antigen in patients suffering from recurrent cold sores and in a series of healthy controls. Paradoxically, all those subject to recurrent herpetic infections had, without exception, evidence of cell-mediated immunity to herpes antigens. This was demonstrated by lymphocyte transformation and specific 51Cr release from infected human amnion cells after incubation with peripheal blood mononuclear cells. Where performed, skin tests with herpes antigen were also positive. In addition, serum from these patients specifically sensitized herpesvirus-infected cells to killing by nonimmune, control mononuclear cells. These tests were negative in the control patients except in a few cases, and it is suggested that these latter may be the asymptomatic herpesvirus carriers previously recognized or that they may have experienced a genital infection.", "contents": "Cell-mediated immunity to Herpes simplex in humans: lymphocyte cytotoxicity measured by 51-Cr release from infected cells. We assessed cell-mediated immunity to herpes simplex virus type 1 antigen in patients suffering from recurrent cold sores and in a series of healthy controls. Paradoxically, all those subject to recurrent herpetic infections had, without exception, evidence of cell-mediated immunity to herpes antigens. This was demonstrated by lymphocyte transformation and specific 51Cr release from infected human amnion cells after incubation with peripheal blood mononuclear cells. Where performed, skin tests with herpes antigen were also positive. In addition, serum from these patients specifically sensitized herpesvirus-infected cells to killing by nonimmune, control mononuclear cells. These tests were negative in the control patients except in a few cases, and it is suggested that these latter may be the asymptomatic herpesvirus carriers previously recognized or that they may have experienced a genital infection."} {"id": "PMID:163221", "title": "Characterization of a Wilms' tumor model.", "content": "Growth characteristics, survival time, sex differences and hormonal effects, and various biochemical parameters were evaluated in a transplantable Furth/Wistar rat Wilms' tumor model. Survival time was dependent on site of tumor transplant and ranged from a mean of 28 days for intrarenal implantation to 44 days intramusculary. Maximum tumor weight (130 g) was obtained via subcutaneous implant. Lung metastasis was evident in the majority of animals with the exception of those receiving the tumor implant intraperitoneally. The levels of erythropoietin and serum calcium and phosphatase were comparable to control values whereas hematocrit levels declined. Tumor tissue arginase or total protein remained unchanged during tumor growth. In these same tissues DNA, content and 5-alpha-reductase activity significantly and progressively increased with concomitant tumor growths. Measurements of lactic dehydrogenase, alkaline phosphatase, and their isoenzymes indicated patterns of liver involvement which were not macroscopically evident. After 31 days of subcutaneous tumor transplant, male and female rats had tumors of comparable weights. Orchiectomy or estradiol treatment significantly reduced tumor weight in males. In female rats testosterone treatment significantly increased tumor weights. DNA concentration in tumor tissue was unaffected by treatment. Similiarly, although 5-alpha-reductase activity was higher in tumors from males, and arginase higher in females, these enzymes were not affected by surgical or hormonal treatment.", "contents": "Characterization of a Wilms' tumor model. Growth characteristics, survival time, sex differences and hormonal effects, and various biochemical parameters were evaluated in a transplantable Furth/Wistar rat Wilms' tumor model. Survival time was dependent on site of tumor transplant and ranged from a mean of 28 days for intrarenal implantation to 44 days intramusculary. Maximum tumor weight (130 g) was obtained via subcutaneous implant. Lung metastasis was evident in the majority of animals with the exception of those receiving the tumor implant intraperitoneally. The levels of erythropoietin and serum calcium and phosphatase were comparable to control values whereas hematocrit levels declined. Tumor tissue arginase or total protein remained unchanged during tumor growth. In these same tissues DNA, content and 5-alpha-reductase activity significantly and progressively increased with concomitant tumor growths. Measurements of lactic dehydrogenase, alkaline phosphatase, and their isoenzymes indicated patterns of liver involvement which were not macroscopically evident. After 31 days of subcutaneous tumor transplant, male and female rats had tumors of comparable weights. Orchiectomy or estradiol treatment significantly reduced tumor weight in males. In female rats testosterone treatment significantly increased tumor weights. DNA concentration in tumor tissue was unaffected by treatment. Similiarly, although 5-alpha-reductase activity was higher in tumors from males, and arginase higher in females, these enzymes were not affected by surgical or hormonal treatment."} {"id": "PMID:163222", "title": "Enzyme histochemical investigation of an adenomatoid tumor.", "content": "Enzyme histochemical study of an adenomatoid tumor of the epididymis revealed an enzyme pattern identical to that of the rete testis. Histogenesis from the same primordium may be suggested.", "contents": "Enzyme histochemical investigation of an adenomatoid tumor. Enzyme histochemical study of an adenomatoid tumor of the epididymis revealed an enzyme pattern identical to that of the rete testis. Histogenesis from the same primordium may be suggested."} {"id": "PMID:163223", "title": "Association of feline leukemia virus with lymphosarcoma and other disorders in the cat.", "content": "Two hundred fifty Boston cats with disorders such as lymphosarcoma, myeloproliferative disease, anemia, glomerulonephritis, pregnancy abnormalities, feline infectious peritonitis, toxoplasmosis, and various bacterial infections were examined for feline leukemia virus (FeLV) by immunofluorescence. Antibody titers against feline oncornavirus-associated cell membrane antigen (FOCMA) were tested in 133 of these cats. The tests for FeLV and FOCMA antibody were also conducted among healthy cats not known to have been exposed to FeLV, as well as among healthy cats from households where FeLV was known to be present. Most of the cats with lymphosarcoma and the other aforementioned disorders were infected with FeLV and low FOCMA antibody titers. Healthy cats known to have been exposed to FeLV were often viremic, but those that remained healthy were able to develop high FOCMA antibody titers. Healthy cats without known prior exposure to FeLV were unlikely to be viremic but often had detectable FOCMA antibody titers, indicating that some exposure occurs under natural conditions in the Boston area. The association of FeLV with infections other than lymphosarcoma was assumed to be caused by the immunosuppresive effect of FeLV, thus allowing development of disease.", "contents": "Association of feline leukemia virus with lymphosarcoma and other disorders in the cat. Two hundred fifty Boston cats with disorders such as lymphosarcoma, myeloproliferative disease, anemia, glomerulonephritis, pregnancy abnormalities, feline infectious peritonitis, toxoplasmosis, and various bacterial infections were examined for feline leukemia virus (FeLV) by immunofluorescence. Antibody titers against feline oncornavirus-associated cell membrane antigen (FOCMA) were tested in 133 of these cats. The tests for FeLV and FOCMA antibody were also conducted among healthy cats not known to have been exposed to FeLV, as well as among healthy cats from households where FeLV was known to be present. Most of the cats with lymphosarcoma and the other aforementioned disorders were infected with FeLV and low FOCMA antibody titers. Healthy cats known to have been exposed to FeLV were often viremic, but those that remained healthy were able to develop high FOCMA antibody titers. Healthy cats without known prior exposure to FeLV were unlikely to be viremic but often had detectable FOCMA antibody titers, indicating that some exposure occurs under natural conditions in the Boston area. The association of FeLV with infections other than lymphosarcoma was assumed to be caused by the immunosuppresive effect of FeLV, thus allowing development of disease."} {"id": "PMID:163224", "title": "Novel pathway for degradation of protocatechuic acid in Bacillus species.", "content": "A species of Bacillus, tentatively identified as B. circulans, degrades protocatechuic acid by a novel reaction involving meta-fission between C2 and C3 of the benzene nucleus. 2-Hydroxymuconic semialdehyde is then degraded to pyruvate and acetaldehyde by enzymatic reactions described in previous work. Protocatechuate 2,3-oxygenase exhibits a rather narrow substrate specificity; the methyl and ethyl esters of protocatechuic acid are oxidized, but other substrates for ring-fission oxygenases, notably catechol, gallic acid, and homoprotocatechuic acid, are not attached.", "contents": "Novel pathway for degradation of protocatechuic acid in Bacillus species. A species of Bacillus, tentatively identified as B. circulans, degrades protocatechuic acid by a novel reaction involving meta-fission between C2 and C3 of the benzene nucleus. 2-Hydroxymuconic semialdehyde is then degraded to pyruvate and acetaldehyde by enzymatic reactions described in previous work. Protocatechuate 2,3-oxygenase exhibits a rather narrow substrate specificity; the methyl and ethyl esters of protocatechuic acid are oxidized, but other substrates for ring-fission oxygenases, notably catechol, gallic acid, and homoprotocatechuic acid, are not attached."} {"id": "PMID:163225", "title": "Circadian rhythms in Neurospora crassa: oscillation in the level of an adenine nucleotide.", "content": "In a mutant strain (bd) of Neurospora, the biological clock is visibly expressed at the growing front of a mycelial mat by sequential periods of conidiating (spore-forming) and non-conidiating growth. The edges (8 mm) of the mycelium at different ages were sampled during a 31 h period, and the adenine nucleotide levels were enzymatically assayed. In the edge region, the total adenosine 5'-monophosphate (AMP) level showed an oscillation, with a minimum of 0.5 mumol/g (residual dry weight) and a maximum of 6.0 mumol/g. The total adenosine 5'-triphosphate level and the total adenosine 5'-diphosphate level showed no obvious oscillation. The oscillation in AMP content had many of the properties of a circadian rhythm. Its period was about 22 h long, it was phase-shifted by light, and it was damped out by continuous illumination. The oscillation in AMP level led to an oscillation in the overall cellular energy charge from 0.65 to 0.93. However, the energy charge calculation does not take into account any possible compartmentalization of AMP, and therefore must be interpretated cautiously. It is suggested that the underlying cause of the oscillation in AMP level could be a rhythmic, partial uncoupling of mitochondrial oxidative phosphorylation.", "contents": "Circadian rhythms in Neurospora crassa: oscillation in the level of an adenine nucleotide. In a mutant strain (bd) of Neurospora, the biological clock is visibly expressed at the growing front of a mycelial mat by sequential periods of conidiating (spore-forming) and non-conidiating growth. The edges (8 mm) of the mycelium at different ages were sampled during a 31 h period, and the adenine nucleotide levels were enzymatically assayed. In the edge region, the total adenosine 5'-monophosphate (AMP) level showed an oscillation, with a minimum of 0.5 mumol/g (residual dry weight) and a maximum of 6.0 mumol/g. The total adenosine 5'-triphosphate level and the total adenosine 5'-diphosphate level showed no obvious oscillation. The oscillation in AMP content had many of the properties of a circadian rhythm. Its period was about 22 h long, it was phase-shifted by light, and it was damped out by continuous illumination. The oscillation in AMP level led to an oscillation in the overall cellular energy charge from 0.65 to 0.93. However, the energy charge calculation does not take into account any possible compartmentalization of AMP, and therefore must be interpretated cautiously. It is suggested that the underlying cause of the oscillation in AMP level could be a rhythmic, partial uncoupling of mitochondrial oxidative phosphorylation."} {"id": "PMID:163226", "title": "Erythritol catabolism by Brucella abortus.", "content": "Cell extracts of Brucella abortus (British 19) catabolized erythritol through a series of phosphorylated intermediates to dihydroxyacetonephosphate and CO-2. Cell extracts required adenosine 5'-triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Mg2+, inorganic orthophosphate, and reduced glutathione for activity. The first reaction in the pathway was the phosphorylation of mesoerythritol with an ATP-dependent kinase which formed d-erythritol 1-phosphate (d-erythro-tetritol 1-phosphate). d-Erythritol 1-phosphate was oxidized by an NAD-dependent dehydrogenase to d-erythrulose 1-phosphate (d-glycero-2-tetrulose 1-phosphate). B. abortus (US-19) was found to lack the succeeding enzyme in the pathway and was used to prepare substrate amounts of d-erythrulose 1-phosphate. d-Erythritol 1-phosphate dehydrogenase (d-erythro-tetritol 1-phosphage: NAD 2-oxidoreductase) is probably membrane bound. d-Erythrulose 1-phosphate was oxidized by an NAD-dependent dehydrogenase to 3-keto-l-erythrose 4-phosphate (l-glycero-3-tetrosulose 4-phosphate) which was further oxidized at C-1 by a membrane-bound dehydrogenase coupled to the electron transport system. Either oxygen or nitrate had to be present as a terminal electron acceptor for the oxidation of 3-keto-l-erythrose 4-phosphate to 3-keto-l-erythronate 4-phosphate (l-glycero-3-tetrulosonic acid 4-phosphate). The beta-keto acid was decarboxylated by a soluble decarboxylase to dihydroxyacetonephosphate and CO-2. Dihydroxyacetonephosphate was converted to pyruvic acid by the final enzymes of glycolysis. The apparent dependence on the electron transport system of erythritol catabolism appears to be unique in Brucella and may play an important role in coupling metabolism to active transport and generation of ATP.", "contents": "Erythritol catabolism by Brucella abortus. Cell extracts of Brucella abortus (British 19) catabolized erythritol through a series of phosphorylated intermediates to dihydroxyacetonephosphate and CO-2. Cell extracts required adenosine 5'-triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Mg2+, inorganic orthophosphate, and reduced glutathione for activity. The first reaction in the pathway was the phosphorylation of mesoerythritol with an ATP-dependent kinase which formed d-erythritol 1-phosphate (d-erythro-tetritol 1-phosphate). d-Erythritol 1-phosphate was oxidized by an NAD-dependent dehydrogenase to d-erythrulose 1-phosphate (d-glycero-2-tetrulose 1-phosphate). B. abortus (US-19) was found to lack the succeeding enzyme in the pathway and was used to prepare substrate amounts of d-erythrulose 1-phosphate. d-Erythritol 1-phosphate dehydrogenase (d-erythro-tetritol 1-phosphage: NAD 2-oxidoreductase) is probably membrane bound. d-Erythrulose 1-phosphate was oxidized by an NAD-dependent dehydrogenase to 3-keto-l-erythrose 4-phosphate (l-glycero-3-tetrosulose 4-phosphate) which was further oxidized at C-1 by a membrane-bound dehydrogenase coupled to the electron transport system. Either oxygen or nitrate had to be present as a terminal electron acceptor for the oxidation of 3-keto-l-erythrose 4-phosphate to 3-keto-l-erythronate 4-phosphate (l-glycero-3-tetrulosonic acid 4-phosphate). The beta-keto acid was decarboxylated by a soluble decarboxylase to dihydroxyacetonephosphate and CO-2. Dihydroxyacetonephosphate was converted to pyruvic acid by the final enzymes of glycolysis. The apparent dependence on the electron transport system of erythritol catabolism appears to be unique in Brucella and may play an important role in coupling metabolism to active transport and generation of ATP."} {"id": "PMID:163227", "title": "Enzymes of deoxythymidine triphosphate biosynthesis in Neurospora crassa mitochondria.", "content": "Intact mitochondria of Neurospora crassa incorporate deoxythymidine 5'-monophosphate (dTMP) into deoxyribonucleic acid but not the label from (methyl-3H) deoxythymidine. Mitochondrial homogenates contain deoxythymidylate kinase (EC 2.7.4.9), deoxycytidylate aminohydrolase (dCMP deaminase) (EC 3.5.4.12), and thymidylate synthetase (EC 2.1.1b), but not thymidine kinase (EC 2.7.1.21) activity. dTMP kinase is loosely bound to the mitochondrial membrane and is solubilized by 0.4 M KCl in mitochondrial homogenates, the dCMP aminohydrolase deaminase) is bound to the inner membrane and is not solubilized by 0.4 M KCl. dTMP synthetase activity is found in the 2,000 times g particulate fractions by homogenization of mitochondria in 0.4 M KCl. The dCMP deaminase activity found in the particulate fraction of the inner membrane is efficiently regulated by the products of the pathway: deoxycytidine 5'-triphosphate activates whereas deoxythymidine 5'-triphosphate inhibits, as found for the soluble enzyme from other sources. These data indicate that mitochondria of N. crassa contain specific enzymes for the biosynthesis of deoxythymidine triphosphate.", "contents": "Enzymes of deoxythymidine triphosphate biosynthesis in Neurospora crassa mitochondria. Intact mitochondria of Neurospora crassa incorporate deoxythymidine 5'-monophosphate (dTMP) into deoxyribonucleic acid but not the label from (methyl-3H) deoxythymidine. Mitochondrial homogenates contain deoxythymidylate kinase (EC 2.7.4.9), deoxycytidylate aminohydrolase (dCMP deaminase) (EC 3.5.4.12), and thymidylate synthetase (EC 2.1.1b), but not thymidine kinase (EC 2.7.1.21) activity. dTMP kinase is loosely bound to the mitochondrial membrane and is solubilized by 0.4 M KCl in mitochondrial homogenates, the dCMP aminohydrolase deaminase) is bound to the inner membrane and is not solubilized by 0.4 M KCl. dTMP synthetase activity is found in the 2,000 times g particulate fractions by homogenization of mitochondria in 0.4 M KCl. The dCMP deaminase activity found in the particulate fraction of the inner membrane is efficiently regulated by the products of the pathway: deoxycytidine 5'-triphosphate activates whereas deoxythymidine 5'-triphosphate inhibits, as found for the soluble enzyme from other sources. These data indicate that mitochondria of N. crassa contain specific enzymes for the biosynthesis of deoxythymidine triphosphate."} {"id": "PMID:163228", "title": "Deoxyribonucleic acid polymerase III of Escherichia coli. Characterization of associated exonuclease activities.", "content": "Purified DNA polymerase III has two distinct exonuclease activities: one initiates hydrolsis at the 3 termini, and the other at the 5 termini of single-stranded DNA. Both exonucleases have the same relative mobility on polyacrylamide gels as the polymerase activity. Molecular identity of the three activities is further indicated by their comparative rates of thermal inactivation and their sensitivity to ionic strength. The 3-5 exonuclease activity hydrolyzes only single-standed DNA. The rate of hydrolysis is twice the optimal rate of polymerization. The products are 5-mononucleotides, but the 3-5 activity is unable to cleave free dinucleotides or the 5-terminal dinucleotide of a polydeoxynucleotide chain. The 3-5 activity will not degrade 3-phosphoryl-terminated oligonucleotides such as d(pTpTpTp). The 5-3 activity catalyzes the hydrolysis of single-stranded DNA at 1/15 the rate of the 3-5 exonuclease. The 5-3 exonuclease requires the presence of a 5 single-stranded terminus in order to initiate hydrolysis, but will thereafter proceed into a double-stranded region. Although the limit products found during hydrolysis of substrates designed to assay specifically the 5-3 activity are predominantly mono- and dinucleotides, these products probably arise from the subsequent hydrolysis of oligonucleotides by the 3-5 hydrolytic activity. This interpretation is supported by (a) the relatively greater activity of the 3-5 exonuclease, (b) the inability of the enzyme to degrade d(pTpTpTp), and (c) the release of the 5 terminus of a single-stranded DNA molecule as an oligonucleotide. The 5-3 exonuclease attacks ultraviolet-irradiated duplex DNA which has first been incised by the Micrococcus luteus endonuclease specific for thymine dimers in DNA.", "contents": "Deoxyribonucleic acid polymerase III of Escherichia coli. Characterization of associated exonuclease activities. Purified DNA polymerase III has two distinct exonuclease activities: one initiates hydrolsis at the 3 termini, and the other at the 5 termini of single-stranded DNA. Both exonucleases have the same relative mobility on polyacrylamide gels as the polymerase activity. Molecular identity of the three activities is further indicated by their comparative rates of thermal inactivation and their sensitivity to ionic strength. The 3-5 exonuclease activity hydrolyzes only single-standed DNA. The rate of hydrolysis is twice the optimal rate of polymerization. The products are 5-mononucleotides, but the 3-5 activity is unable to cleave free dinucleotides or the 5-terminal dinucleotide of a polydeoxynucleotide chain. The 3-5 activity will not degrade 3-phosphoryl-terminated oligonucleotides such as d(pTpTpTp). The 5-3 activity catalyzes the hydrolysis of single-stranded DNA at 1/15 the rate of the 3-5 exonuclease. The 5-3 exonuclease requires the presence of a 5 single-stranded terminus in order to initiate hydrolysis, but will thereafter proceed into a double-stranded region. Although the limit products found during hydrolysis of substrates designed to assay specifically the 5-3 activity are predominantly mono- and dinucleotides, these products probably arise from the subsequent hydrolysis of oligonucleotides by the 3-5 hydrolytic activity. This interpretation is supported by (a) the relatively greater activity of the 3-5 exonuclease, (b) the inability of the enzyme to degrade d(pTpTpTp), and (c) the release of the 5 terminus of a single-stranded DNA molecule as an oligonucleotide. The 5-3 exonuclease attacks ultraviolet-irradiated duplex DNA which has first been incised by the Micrococcus luteus endonuclease specific for thymine dimers in DNA."} {"id": "PMID:163229", "title": "Membrane receptors as general markers for plasma membrane isolation procedures. The use of 125-I-labeled wheat germ agglutinin, insulin, and cholera toxin.", "content": "Specific cell surface membrane receptors, labeled by forming a complex with low concentrations (about 10--9 M to 10--10 M) of a highly radioactive (125-I, carrier-free) ligand, can serve as simple, reliable, sensitive, and quantitative markers for plasma membranes in fractionation procedures. 125-I-Labeled insulin, cholera toxin and the plant lictins, wheat germ agglutinin (WGA), and concanavalin A are the receptor ligands used for labeling plasma membranes. Plasma membranes are labeled before homogenization by incubating intact cells briefly at 24 degrees or 4 degrees, or by very brief in situ perfusion of the organ, with the 125-I-Labeled marker. After removing the free 125-I-labeled ligand from the medium by washing (at 4 degrees), the membrane-marker complex remains intact over prolonged (days) periods of time at 4 degrees. Labeling occurs nearly exclusively on the cell surface, the specificity of this plasma membrane reaction is maintained through homogenization and fractionation, and little dissociation of the complex, detectable exchange of label, or aggregation occur even upon prolonged incubation of the homogenates. When desired, the complex can be dissociated deliberately by manipulating experimental conditions such as temperature or by adding specific simple sugars. The most generally suitable marker appears to be WGA. At least in certain tissues (e. g. fat cells) labeling of the plasma membrane with 125-I-WGA and 125-I-isnulin can be performed equally well and selectively in homogenates as in the intact cell. 125-I-Cholera toxin cannot be used in homogenates because of significant binding to nuclei. The use of 125-I-labeled WGA as a specific plasma membrane marker is illustrated in following the course of fractionations, and in quantitating the yield and purity, of plasma membranes from fat cells, lymphocytes, and liver. The results are compared with simultaneous measurements of the plasma membrane enzyme \"markers,\" ATPase, 5-nucleotidase, and basal as well as hormone-stimulated adenylate cyclase activities. The fractionation of liver plasma membranes by aqueous dextran-polyethylene glycol two-phase polymer systems and by conventional differential centrifugation procedures arealso quantitated with the marker, 125I-WGA. Substantial quantities of plasma membrane material are no recovered in the interphase of the two-phase polymer system. Conventional liver fractionation procedures which retain, for further purification, only the readily sedimented pellet (2000 times g, 15 min) discard a very large (at least 70%) questenal hy", "contents": "Membrane receptors as general markers for plasma membrane isolation procedures. The use of 125-I-labeled wheat germ agglutinin, insulin, and cholera toxin. Specific cell surface membrane receptors, labeled by forming a complex with low concentrations (about 10--9 M to 10--10 M) of a highly radioactive (125-I, carrier-free) ligand, can serve as simple, reliable, sensitive, and quantitative markers for plasma membranes in fractionation procedures. 125-I-Labeled insulin, cholera toxin and the plant lictins, wheat germ agglutinin (WGA), and concanavalin A are the receptor ligands used for labeling plasma membranes. Plasma membranes are labeled before homogenization by incubating intact cells briefly at 24 degrees or 4 degrees, or by very brief in situ perfusion of the organ, with the 125-I-Labeled marker. After removing the free 125-I-labeled ligand from the medium by washing (at 4 degrees), the membrane-marker complex remains intact over prolonged (days) periods of time at 4 degrees. Labeling occurs nearly exclusively on the cell surface, the specificity of this plasma membrane reaction is maintained through homogenization and fractionation, and little dissociation of the complex, detectable exchange of label, or aggregation occur even upon prolonged incubation of the homogenates. When desired, the complex can be dissociated deliberately by manipulating experimental conditions such as temperature or by adding specific simple sugars. The most generally suitable marker appears to be WGA. At least in certain tissues (e. g. fat cells) labeling of the plasma membrane with 125-I-WGA and 125-I-isnulin can be performed equally well and selectively in homogenates as in the intact cell. 125-I-Cholera toxin cannot be used in homogenates because of significant binding to nuclei. The use of 125-I-labeled WGA as a specific plasma membrane marker is illustrated in following the course of fractionations, and in quantitating the yield and purity, of plasma membranes from fat cells, lymphocytes, and liver. The results are compared with simultaneous measurements of the plasma membrane enzyme \"markers,\" ATPase, 5-nucleotidase, and basal as well as hormone-stimulated adenylate cyclase activities. The fractionation of liver plasma membranes by aqueous dextran-polyethylene glycol two-phase polymer systems and by conventional differential centrifugation procedures arealso quantitated with the marker, 125I-WGA. Substantial quantities of plasma membrane material are no recovered in the interphase of the two-phase polymer system. Conventional liver fractionation procedures which retain, for further purification, only the readily sedimented pellet (2000 times g, 15 min) discard a very large (at least 70%) questenal hy"} {"id": "PMID:163230", "title": "The determination of density and molecular weight distributions of lipoproteins by sedimentation equilibrium.", "content": "A method is presented by which an experimental record of total concentration as a function of radial distance, obtained in a sedimentation equilibrium experiment conducted with a noninteracting mixture in the absence of a density gradient, may be analyzed to obtain the unimodal distributions of molecular weight and of partial molar volume when these vary concomitantly and continuously. Particular attention is given to the caracterization of classes of lipoproteins exhibiting Gaussian distributions of these quantities, although the analysis is applicable to other types of unimodal distribution. Equations are also formulated permitting the definition of the corresponding distributions of partial specific volume and of density. The analysis procedure is based on a method (employing Laplace transforms) developed previously, but differs from it in that it avoids the necessity of differentiating experimental results, which introduces error. The method offers certain advantages over other procedures used to characterize and compare lipoprotein samples (exhibiting unimodal distributions) with regard to the duration of the experiment, economy of the sample, and, particularly, the ability to define in principle all of the relevant distributions from one sedimentation equilibrium experiment and an external measurement of the weight average partial specific volume. These points and the steps in the analysis procedure are illustrated with experimental results obtained in the sedimentation equilibrium of a sample of human serum low density lipoprotein. The experimental parameters (such as solution density, column height, and angular velocity) used in the conduction of these experiments were selected on the basis of computer-simulated examples, which are also presented. These provide a guide for other workers interested in characterizing lipoproteins of this class.", "contents": "The determination of density and molecular weight distributions of lipoproteins by sedimentation equilibrium. A method is presented by which an experimental record of total concentration as a function of radial distance, obtained in a sedimentation equilibrium experiment conducted with a noninteracting mixture in the absence of a density gradient, may be analyzed to obtain the unimodal distributions of molecular weight and of partial molar volume when these vary concomitantly and continuously. Particular attention is given to the caracterization of classes of lipoproteins exhibiting Gaussian distributions of these quantities, although the analysis is applicable to other types of unimodal distribution. Equations are also formulated permitting the definition of the corresponding distributions of partial specific volume and of density. The analysis procedure is based on a method (employing Laplace transforms) developed previously, but differs from it in that it avoids the necessity of differentiating experimental results, which introduces error. The method offers certain advantages over other procedures used to characterize and compare lipoprotein samples (exhibiting unimodal distributions) with regard to the duration of the experiment, economy of the sample, and, particularly, the ability to define in principle all of the relevant distributions from one sedimentation equilibrium experiment and an external measurement of the weight average partial specific volume. These points and the steps in the analysis procedure are illustrated with experimental results obtained in the sedimentation equilibrium of a sample of human serum low density lipoprotein. The experimental parameters (such as solution density, column height, and angular velocity) used in the conduction of these experiments were selected on the basis of computer-simulated examples, which are also presented. These provide a guide for other workers interested in characterizing lipoproteins of this class."} {"id": "PMID:163231", "title": "Fluorescent and spin label probes of the environments of the sulfhydryl groups of porcine muscle adenylate kinase.", "content": "The environments of the two sulfhydryl groups of procine muscle adenylate kinase have been investigated by chemical modification reactions. The results indicate that the environments of the two-SH groups of procine muscle adenylate kinase are markedly different and that substrates induce conformational changes in the enzyme in the region of the sulfhydryl groups. The fluorogenic reagent 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-chloride) reacts specifically with the -SH groups of the enzyme at pH 7.9. One thiol group reacts with NBD-chloride approximately 40-fold faster than the other one, and the fast reacting group has been identified as Cys-25 in the amino acid sequence. The similarity of the rate of the more slowly reacting Cys-187 with NBD-chloride to that of glutathione with the same reagent is consistent with its location on the surface of the enzyme as determined by x-ray crystallography structure. The fast reacting Cys-25 in the interior of the structure can be approached by compounds such as NBD-chloride via a cleft. Reaction of Cys-25, presumably located close to the catalytic center, leads to complete inactivation of the enzyme. Substrates such as ATP, MgATP, and ADP which bind to the triphosphate subsite of the enzyme decrease the rate of reaction of Cys-25 by factors up to 3.5 but have only a small effect (approximately equal to 10%) on the reactivity of Cys-187. AMP, however, has a pronounced effect on the reactivity of Cys-187, the slowly reacting group. The multisubstrate analogue P-1, P-5-di-(adenosine-5)pentaphosphate (Ap-5A) decreases the rate of reaction of the fast reacting thiol group by a factor of 300. The behavior of Cys-25 toward NBD-chloride, i.e. super-reactivity in the absense of Ap-5A and slow reactivity in the presence of the multisubstrate inhibitor, was characteristic for both porcin and carp adenylate kinase. In the presence of Ap-5A adenylate kinase can be selectively modified at Cys-187; the introduction of the fluorescent NBD group at this position has no effect on enzymatic activity. A slow transfer of the NBD group occurs from the third groups to the epsilon-amino group of Lys-31. This transfer reaction is further evidence that the structure of adenylate kinase in dilute solution is similar to that of the crystalline enzyme since the x-ray data have shown that the sulfur of Cys-187 and the epsilon-nitrogen of Lys-31 are less than 4 A apart. The strongly fluorescent NBD-NH-enzyme possesses full activity and binds substrates as. cont'd", "contents": "Fluorescent and spin label probes of the environments of the sulfhydryl groups of porcine muscle adenylate kinase. The environments of the two sulfhydryl groups of procine muscle adenylate kinase have been investigated by chemical modification reactions. The results indicate that the environments of the two-SH groups of procine muscle adenylate kinase are markedly different and that substrates induce conformational changes in the enzyme in the region of the sulfhydryl groups. The fluorogenic reagent 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-chloride) reacts specifically with the -SH groups of the enzyme at pH 7.9. One thiol group reacts with NBD-chloride approximately 40-fold faster than the other one, and the fast reacting group has been identified as Cys-25 in the amino acid sequence. The similarity of the rate of the more slowly reacting Cys-187 with NBD-chloride to that of glutathione with the same reagent is consistent with its location on the surface of the enzyme as determined by x-ray crystallography structure. The fast reacting Cys-25 in the interior of the structure can be approached by compounds such as NBD-chloride via a cleft. Reaction of Cys-25, presumably located close to the catalytic center, leads to complete inactivation of the enzyme. Substrates such as ATP, MgATP, and ADP which bind to the triphosphate subsite of the enzyme decrease the rate of reaction of Cys-25 by factors up to 3.5 but have only a small effect (approximately equal to 10%) on the reactivity of Cys-187. AMP, however, has a pronounced effect on the reactivity of Cys-187, the slowly reacting group. The multisubstrate analogue P-1, P-5-di-(adenosine-5)pentaphosphate (Ap-5A) decreases the rate of reaction of the fast reacting thiol group by a factor of 300. The behavior of Cys-25 toward NBD-chloride, i.e. super-reactivity in the absense of Ap-5A and slow reactivity in the presence of the multisubstrate inhibitor, was characteristic for both porcin and carp adenylate kinase. In the presence of Ap-5A adenylate kinase can be selectively modified at Cys-187; the introduction of the fluorescent NBD group at this position has no effect on enzymatic activity. A slow transfer of the NBD group occurs from the third groups to the epsilon-amino group of Lys-31. This transfer reaction is further evidence that the structure of adenylate kinase in dilute solution is similar to that of the crystalline enzyme since the x-ray data have shown that the sulfur of Cys-187 and the epsilon-nitrogen of Lys-31 are less than 4 A apart. The strongly fluorescent NBD-NH-enzyme possesses full activity and binds substrates as. cont'd"} {"id": "PMID:163232", "title": "A guanosine 3':5'-monophosphate-sensitive nuclease from Bacillus brevis.", "content": "In toluene-treated cells of Bacillus brevis, newly synthesized RNA is rapidly degraded in a reaction that is inhibited by cyclic guanosine 3':5'-monophosphate (cGMP) and by 1,10-phenanthroline. This appears to be due to a ribonuclease found in cell-free extracts of B. brevis which is inhibited by cGMP and related compounds as well as by 1,10-phenanthroline. The cGMP-sensitive nuclease hydrolyzes synthetic polynucleotides, yielding nucleoside 5'-monophosphates as the sole products, even during the early stages of hydrolysis. Synthetic polynucleotides terminated by a 3'-phosphate are resistant to hydrolysis. While with 3'-hydrolysis of the polymer. The enzyme is therefore an exonuclease that degrades polynucleotides from the 3' end to product 5'-mononucleotides. It also acts on denatured but not on native DNA. Activity is greatest in the presence of Mn2+ and is not affected by the presence of monovalent cations. 1,10-Phenanthroline, but not 1,7-phenanthroline, inhibits the nuclease even when Mn2+ is present in excess. The inhibition of the enzyme by cGMP is noncompetitive, and cGMP itself is not hydrolyzed. The sensitivity of the nuclease to inhibition depends strikingly on the nature of the substrate and is lost when the enzyme is assayed at high pH. These observations suggest that cGMP inhibits the nuclease by combining with an allosteric site on the enzyme. Although cGMP was found to be the most effective inhibitor, other nucleoside 3':5'-monophosphates and derivatives of 5'-GMP can also inhibit the nuclease. Since measurements of cGMP in B. brevis have not revealed detectable amounts (less than 5 times 10-8 M), the substance that modulates the activity of the nuclease under physiological conditions remains to be identified.", "contents": "A guanosine 3':5'-monophosphate-sensitive nuclease from Bacillus brevis. In toluene-treated cells of Bacillus brevis, newly synthesized RNA is rapidly degraded in a reaction that is inhibited by cyclic guanosine 3':5'-monophosphate (cGMP) and by 1,10-phenanthroline. This appears to be due to a ribonuclease found in cell-free extracts of B. brevis which is inhibited by cGMP and related compounds as well as by 1,10-phenanthroline. The cGMP-sensitive nuclease hydrolyzes synthetic polynucleotides, yielding nucleoside 5'-monophosphates as the sole products, even during the early stages of hydrolysis. Synthetic polynucleotides terminated by a 3'-phosphate are resistant to hydrolysis. While with 3'-hydrolysis of the polymer. The enzyme is therefore an exonuclease that degrades polynucleotides from the 3' end to product 5'-mononucleotides. It also acts on denatured but not on native DNA. Activity is greatest in the presence of Mn2+ and is not affected by the presence of monovalent cations. 1,10-Phenanthroline, but not 1,7-phenanthroline, inhibits the nuclease even when Mn2+ is present in excess. The inhibition of the enzyme by cGMP is noncompetitive, and cGMP itself is not hydrolyzed. The sensitivity of the nuclease to inhibition depends strikingly on the nature of the substrate and is lost when the enzyme is assayed at high pH. These observations suggest that cGMP inhibits the nuclease by combining with an allosteric site on the enzyme. Although cGMP was found to be the most effective inhibitor, other nucleoside 3':5'-monophosphates and derivatives of 5'-GMP can also inhibit the nuclease. Since measurements of cGMP in B. brevis have not revealed detectable amounts (less than 5 times 10-8 M), the substance that modulates the activity of the nuclease under physiological conditions remains to be identified."} {"id": "PMID:163233", "title": "Cytochrome c oxidase from bakers' yeast. III. Physical characterization of isolated subunits and chemical evidence for two different classes of polypeptides.", "content": "Earlier studies have shown that cytochrome c oxidase from bakers' yeast is an oligomeric enzyme which contains three polypeptides (I to III) synthesized on mitochondrial ribosomes and four polypeptides (IV to VII) synthesized on cytoplasmic ribosomes. These polypeptide subunits have now been isolated by a simple protocol which utilizes differences in polypeptide charge, solubility, and size. Their molecular weights determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, gel filtration in the presence of guanidine hydrochloride, and amino acid analysis were: I, 40,000; II, 33,000; III, 22,000; IV, 14,500; V, 12,700; VI, 12,700; and VII, 4,600. All seven polypeptide subunits exhibited acidic isoelectric points; cytoplasmically made subunits were more acidic than mitochondrially made ones. The amino acid composition of two mitochondrially made subunits and two cytoplasmically made subunits was determined. The two mitochondrial translation products, I and II, contained only 34.7% and 42.1% polar amino acids, respectively, whereas the two cytoplasmic translation products, IV and VI, contained 48.3% and 49.3%, respectively. This agreed with the observation that Subunits I and II are very insoluble, requiring detergents for solubility, whereas Subunits IV and VI are water-soluble in the absence of any added detergent. These results indicate that the cytochrome c oxidase subunits synthesized on mitochondrial and cytoplasmic ribosomes are fundamentally different in size, isoelectric properties, and hydrophobicity. They also suggest the possibility that at least some of the mitochondrially made subunits are buried in the lipid phase of the mitochondrial inner membrane.", "contents": "Cytochrome c oxidase from bakers' yeast. III. Physical characterization of isolated subunits and chemical evidence for two different classes of polypeptides. Earlier studies have shown that cytochrome c oxidase from bakers' yeast is an oligomeric enzyme which contains three polypeptides (I to III) synthesized on mitochondrial ribosomes and four polypeptides (IV to VII) synthesized on cytoplasmic ribosomes. These polypeptide subunits have now been isolated by a simple protocol which utilizes differences in polypeptide charge, solubility, and size. Their molecular weights determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, gel filtration in the presence of guanidine hydrochloride, and amino acid analysis were: I, 40,000; II, 33,000; III, 22,000; IV, 14,500; V, 12,700; VI, 12,700; and VII, 4,600. All seven polypeptide subunits exhibited acidic isoelectric points; cytoplasmically made subunits were more acidic than mitochondrially made ones. The amino acid composition of two mitochondrially made subunits and two cytoplasmically made subunits was determined. The two mitochondrial translation products, I and II, contained only 34.7% and 42.1% polar amino acids, respectively, whereas the two cytoplasmic translation products, IV and VI, contained 48.3% and 49.3%, respectively. This agreed with the observation that Subunits I and II are very insoluble, requiring detergents for solubility, whereas Subunits IV and VI are water-soluble in the absence of any added detergent. These results indicate that the cytochrome c oxidase subunits synthesized on mitochondrial and cytoplasmic ribosomes are fundamentally different in size, isoelectric properties, and hydrophobicity. They also suggest the possibility that at least some of the mitochondrially made subunits are buried in the lipid phase of the mitochondrial inner membrane."} {"id": "PMID:163234", "title": "Cytochrome c oxidase from bakers' yeast. IV. Immunological evidence for the participation of a mitochondrially synthesized subunit in enzymatic activity.", "content": "In order to study the role of the individual subunits of yeast cytochrome c oxidase, rabbit antisera were prepared against Subunit II (a mitochondrially made polypeptide) and Subunit VI (a cytoplasmically made polypeptide). Antisera were also obtained against a mixture of the two mitochondrially made subunits (I PLUS II) and against mixtures of the following cytoplasmically made subunits: (IV PLUS VI); (V PLUS VII); and (IV PLUS V PLUS VI PLUS VII). Neither anti-II serum nor anti-VI serum cross-reacted with any of the other six subunits of cytochrome c oxidase as judged by a sensitive ring test or by double diffusion in agarose gels. Anti-II serum inhibited the oxidation of ferrocytochrome c by purified yeast cytochrome c oxidase or by freshly isolated as well as sonically fragmented yeast mitochondria. Anti-(V, VII) serum and anti-(IV, V, VI, VII) serum were also strongly inhibitory. Anti-VI serum and anti-(IV, VI) serum inhibited only weakly. If purified cytochrome c oxidase was inhibited with a saturating amount of anti-VI serum, anti-II serum elicited a further increment of inhibition, as would be expected if the inhibitory effects of these two antisera involved different antigenic sites on the holoenzyme. Each of the antisera precipitated all seven cytochrome c oxidase subunits from crude mitochondrial extracts. However, anti-VI and, particularly, anti-II were much less effective precipitants than antisera against Subunits IV to VII or antisera against the holoenzyme. These data suggest that the oxidation of ferrocytochrome c by cytochrome c oxidase required both mitochondrially as well as cytoplasmically made subunits.", "contents": "Cytochrome c oxidase from bakers' yeast. IV. Immunological evidence for the participation of a mitochondrially synthesized subunit in enzymatic activity. In order to study the role of the individual subunits of yeast cytochrome c oxidase, rabbit antisera were prepared against Subunit II (a mitochondrially made polypeptide) and Subunit VI (a cytoplasmically made polypeptide). Antisera were also obtained against a mixture of the two mitochondrially made subunits (I PLUS II) and against mixtures of the following cytoplasmically made subunits: (IV PLUS VI); (V PLUS VII); and (IV PLUS V PLUS VI PLUS VII). Neither anti-II serum nor anti-VI serum cross-reacted with any of the other six subunits of cytochrome c oxidase as judged by a sensitive ring test or by double diffusion in agarose gels. Anti-II serum inhibited the oxidation of ferrocytochrome c by purified yeast cytochrome c oxidase or by freshly isolated as well as sonically fragmented yeast mitochondria. Anti-(V, VII) serum and anti-(IV, V, VI, VII) serum were also strongly inhibitory. Anti-VI serum and anti-(IV, VI) serum inhibited only weakly. If purified cytochrome c oxidase was inhibited with a saturating amount of anti-VI serum, anti-II serum elicited a further increment of inhibition, as would be expected if the inhibitory effects of these two antisera involved different antigenic sites on the holoenzyme. Each of the antisera precipitated all seven cytochrome c oxidase subunits from crude mitochondrial extracts. However, anti-VI and, particularly, anti-II were much less effective precipitants than antisera against Subunits IV to VII or antisera against the holoenzyme. These data suggest that the oxidation of ferrocytochrome c by cytochrome c oxidase required both mitochondrially as well as cytoplasmically made subunits."} {"id": "PMID:163235", "title": "Cytochrome c oxidase from bakers' yeast. V. Arrangement of the subunits in the isolated and membrane-bound enzyme.", "content": "Cytochrome c oxidase from baker's yeast contains three mitochondrially made subunits (I to III) which are relatively hydrophobic and four cytoplasmically made subunits (IV to VII) which are relatively hydrophilic (Mason, T. L., Poyton, R. O., Wharton, D.C., and Schatz, G. (1973) J. Biol. Chem. 248, 1346-1354 and Poyton, R. O., and Schatz, G. (1975) J. Biol. Chem. 250, 752-761). In order to explore the arrangement of these subunits in the holoenzyme, the reactivity of each subunit with a variety of \"surface probes\" was tested with isolated cytochrome c oxidase, with cytochrome c oxidase incorporated into liposomes, and with mitochondrially bound cytochrome c oxidase. The surface probes included iodination with lactoperoxidase and coupling with p-diazonium benzenesulfonate. In addition, external subunits were identified by linking them to bovine serum albumin carrying a covalently bound isocyanate group. In the membrane-bound enzyme, Subunit I was almost completely inaccessible and Subunit II was partly inaccessible to all surface probes. All of the other subunits were accessible. Similar results were obtained with the solubilized enzyme, except that the differences in reactivity between the individual subunits were less clear-cut. The results obtained with liposome-bound cytochrome c oxidase resembled those obtained with the mitochondrially bound enzyme. These data suggest that the two largest mitochondrially made subunits are localized in the interior of the enzyme and that they are genuine components of cytochrome c oxidase.", "contents": "Cytochrome c oxidase from bakers' yeast. V. Arrangement of the subunits in the isolated and membrane-bound enzyme. Cytochrome c oxidase from baker's yeast contains three mitochondrially made subunits (I to III) which are relatively hydrophobic and four cytoplasmically made subunits (IV to VII) which are relatively hydrophilic (Mason, T. L., Poyton, R. O., Wharton, D.C., and Schatz, G. (1973) J. Biol. Chem. 248, 1346-1354 and Poyton, R. O., and Schatz, G. (1975) J. Biol. Chem. 250, 752-761). In order to explore the arrangement of these subunits in the holoenzyme, the reactivity of each subunit with a variety of \"surface probes\" was tested with isolated cytochrome c oxidase, with cytochrome c oxidase incorporated into liposomes, and with mitochondrially bound cytochrome c oxidase. The surface probes included iodination with lactoperoxidase and coupling with p-diazonium benzenesulfonate. In addition, external subunits were identified by linking them to bovine serum albumin carrying a covalently bound isocyanate group. In the membrane-bound enzyme, Subunit I was almost completely inaccessible and Subunit II was partly inaccessible to all surface probes. All of the other subunits were accessible. Similar results were obtained with the solubilized enzyme, except that the differences in reactivity between the individual subunits were less clear-cut. The results obtained with liposome-bound cytochrome c oxidase resembled those obtained with the mitochondrially bound enzyme. These data suggest that the two largest mitochondrially made subunits are localized in the interior of the enzyme and that they are genuine components of cytochrome c oxidase."} {"id": "PMID:163236", "title": "Mitochondrial assembly in respiration-deficient mutants of Saccharomyces cerevisiae. IV. Effects of nuclear amber suppressors on the accumulation of a mitochondrially made subunit of cytochrome c oxidase.", "content": "Earlier studies from this laboratory have shown that cytochrome c oxidase from bakers' yeast contains seven subunits, three of which are made in the mitochondrion (Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 1355). Moreover, a cytochrome c oxidase-less yeast mutant (pet 494-1) was isolated which lacked one of the mitochondrially made subunits (Ebner, E., Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 5369). Surprisingly, the mutated gene was localized in the nucleus. The results presented here demonstrate that this mutant phenotype can be suppressed by nuclear amber suppressors which affect translation on cytoplasmic ribosomes. This fact was established by two methods, (a) By constructing pet 494-1 strains possessing various amber and ochre markers, isolating respiring revertants from these strains, and demonstrating co-reversion of the amber (but not of the ochre) markers. (b) By coupling the pet 494-1 allele with the well characterized amber suppressor gene SUP 4-3. These data show that suppressor genes located on nuclear chromosomes may control the accumulation of a mitochondrially synthesized polypeptide. The present results also allow some tentative conclusions about the mechanism of the pet 494 mutation. Because it is highly unlikely that the cytoplasmic and the mitochondrial translation system share a common suppressor, the pet 494 locus probably does not code for the missing mitochondrially made subunit, but for a cytoplasmically made protein. This as yet unidentified protein seems to control the synthesis or the integration of the mitochondrially made subunit. Nuclear suppressor genes may thus be useful tools for studying the role of cytoplasmic protein synthesis in mitochondrial formation.", "contents": "Mitochondrial assembly in respiration-deficient mutants of Saccharomyces cerevisiae. IV. Effects of nuclear amber suppressors on the accumulation of a mitochondrially made subunit of cytochrome c oxidase. Earlier studies from this laboratory have shown that cytochrome c oxidase from bakers' yeast contains seven subunits, three of which are made in the mitochondrion (Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 1355). Moreover, a cytochrome c oxidase-less yeast mutant (pet 494-1) was isolated which lacked one of the mitochondrially made subunits (Ebner, E., Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 5369). Surprisingly, the mutated gene was localized in the nucleus. The results presented here demonstrate that this mutant phenotype can be suppressed by nuclear amber suppressors which affect translation on cytoplasmic ribosomes. This fact was established by two methods, (a) By constructing pet 494-1 strains possessing various amber and ochre markers, isolating respiring revertants from these strains, and demonstrating co-reversion of the amber (but not of the ochre) markers. (b) By coupling the pet 494-1 allele with the well characterized amber suppressor gene SUP 4-3. These data show that suppressor genes located on nuclear chromosomes may control the accumulation of a mitochondrially synthesized polypeptide. The present results also allow some tentative conclusions about the mechanism of the pet 494 mutation. Because it is highly unlikely that the cytoplasmic and the mitochondrial translation system share a common suppressor, the pet 494 locus probably does not code for the missing mitochondrially made subunit, but for a cytoplasmically made protein. This as yet unidentified protein seems to control the synthesis or the integration of the mitochondrially made subunit. Nuclear suppressor genes may thus be useful tools for studying the role of cytoplasmic protein synthesis in mitochondrial formation."} {"id": "PMID:163237", "title": "The interaction of histones with simian virus 40 supercoiled circular deoxyribonucleic acid in vitro.", "content": "The interaction of supercoiled, circular SV40 DNA with calf thymus histone fractions has been studied. Five- to ten-fold less f1 histone is required to complex a given amount of DNA compared to the other histones. When the supercoiled DNA is converted to either the relaxed circular form, or full length linear molecules, or gragmented linear or denatured stands, the efficiency of complex formation with f1 histone markedly decreases. We conclude that f1 histone has a special ability to interact with supercoiled DNA. This conclusion is supported by the fact that supercoiled circular Col E1 DNA interacts with f1 as efficiently as does SV40 DNA.", "contents": "The interaction of histones with simian virus 40 supercoiled circular deoxyribonucleic acid in vitro. The interaction of supercoiled, circular SV40 DNA with calf thymus histone fractions has been studied. Five- to ten-fold less f1 histone is required to complex a given amount of DNA compared to the other histones. When the supercoiled DNA is converted to either the relaxed circular form, or full length linear molecules, or gragmented linear or denatured stands, the efficiency of complex formation with f1 histone markedly decreases. We conclude that f1 histone has a special ability to interact with supercoiled DNA. This conclusion is supported by the fact that supercoiled circular Col E1 DNA interacts with f1 as efficiently as does SV40 DNA."} {"id": "PMID:163238", "title": "The \"activated\" hepatic glucocorticoid-receptor complex. Its generation and properties.", "content": "The glucocorticoid receptor-glucocorticoid complex of the hepatic cytosol need undergo an \"activation\" to enable its binding to nuclei, chromatin, or stripped DNA. The conditions of this activation have been studied using native calf thymus DNA absorbed to cellulose. At low ionic strength, activation is very slow at 0 degrees, but, takes place rapidly at 25 degrees, reaching completion at 1 hour. Addition of 10 mm CaCl2 or 150 mm NaCl increases the rate of activation of the receptor at 0 degrees. Neither magnesium nor manganese ions can replace calcium with respect to enabling activation of the steroid-receptor complex to occur at low temperatures. Isofocusing studies reveal that the major component of the unactivated steroid-receptor complex has an isoelectric point of 7.1. Incubation of the steroid-receptor complex at 25 degrees for 30 min leads to its conversion to a form with an isoelectric point of 6.1 concurrent with the development of its ability to bind to DNA-cellulose. Sucrose density gradient analysis reveals that no detectable alteration in the sedimentation coefficient of the steroid-receptor complex occurs during its activation. MnCl2 (20mm) effeciently precipitates the unactivated hormone-receptor complex and to a lesser degree, precipitates the activated hormone-receptor complex.", "contents": "The \"activated\" hepatic glucocorticoid-receptor complex. Its generation and properties. The glucocorticoid receptor-glucocorticoid complex of the hepatic cytosol need undergo an \"activation\" to enable its binding to nuclei, chromatin, or stripped DNA. The conditions of this activation have been studied using native calf thymus DNA absorbed to cellulose. At low ionic strength, activation is very slow at 0 degrees, but, takes place rapidly at 25 degrees, reaching completion at 1 hour. Addition of 10 mm CaCl2 or 150 mm NaCl increases the rate of activation of the receptor at 0 degrees. Neither magnesium nor manganese ions can replace calcium with respect to enabling activation of the steroid-receptor complex to occur at low temperatures. Isofocusing studies reveal that the major component of the unactivated steroid-receptor complex has an isoelectric point of 7.1. Incubation of the steroid-receptor complex at 25 degrees for 30 min leads to its conversion to a form with an isoelectric point of 6.1 concurrent with the development of its ability to bind to DNA-cellulose. Sucrose density gradient analysis reveals that no detectable alteration in the sedimentation coefficient of the steroid-receptor complex occurs during its activation. MnCl2 (20mm) effeciently precipitates the unactivated hormone-receptor complex and to a lesser degree, precipitates the activated hormone-receptor complex."} {"id": "PMID:163239", "title": "Progesterone-binding components of chick oviduct. VIII. Receptor activation and hormone-dependent binding to purified nuclei.", "content": "A cell-free system prepared from the estrogen-primed chick oviduct was developed and used to study the uptake of cytoplasmic progesterone-receptor complex by isolated nuclei. The receptor and purified nuclei were shown to be stable at 25 degrees, but not at 37 degrees. Thus, nuclear incubations were routinely performed at 25 degrees. Such incubations revealed greater nuclear uptake of the cytoplasmic hormone-receptor complex as compared to control incubations performed at 0 degrees. The uptake process showed a quantitative preference for oviduct nuclei. No net uptake occurred during 0 degrees incubations when the nuclei were preincubated in the absence of cytoplasmic components at 25 degrees. In contrast, the temperature requirement was partially removed by preincubation of the hormone-receptor complex at 25 degrees prior to incubation with nuclei at 0 degrees. Nuclear uptake was not accompanied by measurable alterations in the sedimentation properties of the progesterone receptor. The activation and nuclear uptake of receptor was clearly dependent upon prior binding of steroid hormone to the receptor indicating that the active nuclear form of the receptor could not be generated in the absence of the hormone. Receptor precipitation with ammonium sulfate also partially removed the temperature requirement for nuclear binding. In contrast to temperature activation, ammonium sulfate precipitation activated the receptor in the absence of hormone. It thus seemed likely that temperature and salt activation of receptor occurred via different mechanisms. Although we were able to destroy up to 60% of the nuclear DNA content by treatment with DNase prior to nuclear incubation, some 80 to 85% of the receptor-binding capacity was still present in the treated nuclei. Thus, chick progesterone receptors apparently bind to a relatively DNase-resistant portion of the oviduct genome. The properties of this system indicate its value for further investigation into the initial events of progesterone action in the chick oviduct.", "contents": "Progesterone-binding components of chick oviduct. VIII. Receptor activation and hormone-dependent binding to purified nuclei. A cell-free system prepared from the estrogen-primed chick oviduct was developed and used to study the uptake of cytoplasmic progesterone-receptor complex by isolated nuclei. The receptor and purified nuclei were shown to be stable at 25 degrees, but not at 37 degrees. Thus, nuclear incubations were routinely performed at 25 degrees. Such incubations revealed greater nuclear uptake of the cytoplasmic hormone-receptor complex as compared to control incubations performed at 0 degrees. The uptake process showed a quantitative preference for oviduct nuclei. No net uptake occurred during 0 degrees incubations when the nuclei were preincubated in the absence of cytoplasmic components at 25 degrees. In contrast, the temperature requirement was partially removed by preincubation of the hormone-receptor complex at 25 degrees prior to incubation with nuclei at 0 degrees. Nuclear uptake was not accompanied by measurable alterations in the sedimentation properties of the progesterone receptor. The activation and nuclear uptake of receptor was clearly dependent upon prior binding of steroid hormone to the receptor indicating that the active nuclear form of the receptor could not be generated in the absence of the hormone. Receptor precipitation with ammonium sulfate also partially removed the temperature requirement for nuclear binding. In contrast to temperature activation, ammonium sulfate precipitation activated the receptor in the absence of hormone. It thus seemed likely that temperature and salt activation of receptor occurred via different mechanisms. Although we were able to destroy up to 60% of the nuclear DNA content by treatment with DNase prior to nuclear incubation, some 80 to 85% of the receptor-binding capacity was still present in the treated nuclei. Thus, chick progesterone receptors apparently bind to a relatively DNase-resistant portion of the oviduct genome. The properties of this system indicate its value for further investigation into the initial events of progesterone action in the chick oviduct."} {"id": "PMID:163240", "title": "Progesterone-binding components of chick oviduct. IX. The kinetics of nuclear binding.", "content": "A cell-free system was used to study the kinetics of progesterone-receptor interaction with purified nuclei prepared from estrogen-primed chick oviducts. The binding process was a saturable phenomenon in both target and nontarget tissues. More nuclear acceptor sites were available to target tissue (similar to 9000 sites per oviduct nucleus) than in nontarget tissues (similar to 1000 to 3000 sites per nucleus), but the binding constant was essentially the same (Kd similar to 10-8 M). A second much smaller class of higher affinity sites (Kd similar to 10-11M) may exist. Its presence was detected by Scatchard plot nonlinearity at very low concentrations of added receptor-hormone complex (similar to 10-10 to 10-12M). The current study focused on the prevalent class of acceptor sites which was more readily detectable. Receptor binding to these sites was highly sensitive to salt. More sites were exposed at 25 degrees than at 0 degrees. Binding to these sites was inhibited in a nonselective fashion by the addition of protein. Although receptors may be activated by temperature or conditions of high ionic strength, these conditions could not capacitate more than 30 to 40% of the progesterone-receptor proteins for binding. Rate studies suggested that temperature plays a minimal role in nuclear uptake of activated receptors. Such a finding is consistent with a diffusion-limited uptake process.", "contents": "Progesterone-binding components of chick oviduct. IX. The kinetics of nuclear binding. A cell-free system was used to study the kinetics of progesterone-receptor interaction with purified nuclei prepared from estrogen-primed chick oviducts. The binding process was a saturable phenomenon in both target and nontarget tissues. More nuclear acceptor sites were available to target tissue (similar to 9000 sites per oviduct nucleus) than in nontarget tissues (similar to 1000 to 3000 sites per nucleus), but the binding constant was essentially the same (Kd similar to 10-8 M). A second much smaller class of higher affinity sites (Kd similar to 10-11M) may exist. Its presence was detected by Scatchard plot nonlinearity at very low concentrations of added receptor-hormone complex (similar to 10-10 to 10-12M). The current study focused on the prevalent class of acceptor sites which was more readily detectable. Receptor binding to these sites was highly sensitive to salt. More sites were exposed at 25 degrees than at 0 degrees. Binding to these sites was inhibited in a nonselective fashion by the addition of protein. Although receptors may be activated by temperature or conditions of high ionic strength, these conditions could not capacitate more than 30 to 40% of the progesterone-receptor proteins for binding. Rate studies suggested that temperature plays a minimal role in nuclear uptake of activated receptors. Such a finding is consistent with a diffusion-limited uptake process."} {"id": "PMID:163241", "title": "Role of metal ions in Escherichia coli alkaline phosphatase. A study of the metal-water interaction by nuclear relaxation rate measurements on water protons.", "content": "The binding of metal to alkaline phosphatase from Escherichia coli and the binding of water and orthophosphate to the Me-2+-enzyme binary complex have been examined by water proton relaxation rate (PRR) measurements. Titration of the three paramagnetic metals, Mn2+, Cu2+, and Co2+, into apoalkaline phosphatase and the titrations of apoenzyme into metal have been carried out. Analysis of the spin-lattice relaxation rates for these titrations and of Scatchard binding curves derived from these results, as well as EPR data, show four tight manganese sites, between two and three tight copper sites, or four cobalt sites per enzyme dimer of molecular weight 80,000. The multiple sites for each metal are indistinguishable by these magnetic resonance techniques. Both the spin-lattice- and spin-spin-relaxation rates exhibit a negative temperature coefficient, showing that these processes are not exchange-limited. From a frequency dependence study of T-1 and from the T-1:T-2 ratio measured at 220 MHz, correlation times from the water-enzyme complexes have been estimated. For H20-Mn-2+-alkaline phosphatase, gamma c equals 1.55 times 10-9 s; for H20-Cu-2+ -alkaline phosphatase, gamma c equals 1.82 times 10-s; and for the cobalt complex, gamma c equals 1.0 times 10-12 s at 4 degrees. Assuming 1 water molecule bound per metal site, these correlation times correspond to the following water-metal distances: gamma (A) is 4.0 A for Mn-2+-H20, 3.4 A for Cu-2+-H20, and 2.8 A for Co-2+-H20. Thus, water is shown to bind directly to the metal atoms of alkaline phosphatase. The correlation between the length of the water-metal bond and the relative activity of the various metalloenzymes support the importance of this binding in the monophosphoesterase reaction catalyzed by alkaline phosphatase. Addition of excess orthophosphate to any of the water-metalloenzyme complexes does not displace an exchangeable water molecule from the metal site. The Mn-PO-4 distance which we have reported earlier (Zukin, R.S., Hollis, D.P., and Gray, G.A. (1973) Biochem. Biophys. Res. Commun. 53, 238) to be 7.3 A is consistent with this finding and suggests a model in which Pi binds to Mn-2+-alkaline phosphatase through a water bridge.", "contents": "Role of metal ions in Escherichia coli alkaline phosphatase. A study of the metal-water interaction by nuclear relaxation rate measurements on water protons. The binding of metal to alkaline phosphatase from Escherichia coli and the binding of water and orthophosphate to the Me-2+-enzyme binary complex have been examined by water proton relaxation rate (PRR) measurements. Titration of the three paramagnetic metals, Mn2+, Cu2+, and Co2+, into apoalkaline phosphatase and the titrations of apoenzyme into metal have been carried out. Analysis of the spin-lattice relaxation rates for these titrations and of Scatchard binding curves derived from these results, as well as EPR data, show four tight manganese sites, between two and three tight copper sites, or four cobalt sites per enzyme dimer of molecular weight 80,000. The multiple sites for each metal are indistinguishable by these magnetic resonance techniques. Both the spin-lattice- and spin-spin-relaxation rates exhibit a negative temperature coefficient, showing that these processes are not exchange-limited. From a frequency dependence study of T-1 and from the T-1:T-2 ratio measured at 220 MHz, correlation times from the water-enzyme complexes have been estimated. For H20-Mn-2+-alkaline phosphatase, gamma c equals 1.55 times 10-9 s; for H20-Cu-2+ -alkaline phosphatase, gamma c equals 1.82 times 10-s; and for the cobalt complex, gamma c equals 1.0 times 10-12 s at 4 degrees. Assuming 1 water molecule bound per metal site, these correlation times correspond to the following water-metal distances: gamma (A) is 4.0 A for Mn-2+-H20, 3.4 A for Cu-2+-H20, and 2.8 A for Co-2+-H20. Thus, water is shown to bind directly to the metal atoms of alkaline phosphatase. The correlation between the length of the water-metal bond and the relative activity of the various metalloenzymes support the importance of this binding in the monophosphoesterase reaction catalyzed by alkaline phosphatase. Addition of excess orthophosphate to any of the water-metalloenzyme complexes does not displace an exchangeable water molecule from the metal site. The Mn-PO-4 distance which we have reported earlier (Zukin, R.S., Hollis, D.P., and Gray, G.A. (1973) Biochem. Biophys. Res. Commun. 53, 238) to be 7.3 A is consistent with this finding and suggests a model in which Pi binds to Mn-2+-alkaline phosphatase through a water bridge."} {"id": "PMID:163242", "title": "The interaction of inhibitors of proteolytic enzymes with 3-methylhistidine-57-chymotrypsin.", "content": "The inhibition of proteolytic enzymes by protein inhibitors is accompanied by the formation of unusually stable complexes. The recognition of a specific substrate-like amino acid on the inhibitor is believed to be the initial event of the inhibitory process. In addition to the interactions involved in the binding of a good substrate, a variety of other noncovalent interactions are known to stabilize the complex. The formation of stable complexes between several inactive derivatives of proteolytic enzymes and a variety of protein inhibitors suggests strongly that the formation of any species resembling catalytic intermediates is unnecessary for inhibition. We have examined the interaction between several avian ovomucoids and alpha-chymotrypsin in which histidine-57 has been converted to 3-methylhistidine-57. This derivative is easily prepared and can be isolated by affinity chromatography. Methylchymotrypsin retains unaltered its ability to bind specific substrates, but is essentially inactive. In spite of this loss of enzymatic activity, methylchymotrypsin forms strong complexes with several inhibitors. In addition, methylchymotrypsin which has been covalently linked to Sepharose is particularly useful for the isolation of protein inhibitors without the complications due to isolation of a mixture of partially cleaved forms of the inhibitor.", "contents": "The interaction of inhibitors of proteolytic enzymes with 3-methylhistidine-57-chymotrypsin. The inhibition of proteolytic enzymes by protein inhibitors is accompanied by the formation of unusually stable complexes. The recognition of a specific substrate-like amino acid on the inhibitor is believed to be the initial event of the inhibitory process. In addition to the interactions involved in the binding of a good substrate, a variety of other noncovalent interactions are known to stabilize the complex. The formation of stable complexes between several inactive derivatives of proteolytic enzymes and a variety of protein inhibitors suggests strongly that the formation of any species resembling catalytic intermediates is unnecessary for inhibition. We have examined the interaction between several avian ovomucoids and alpha-chymotrypsin in which histidine-57 has been converted to 3-methylhistidine-57. This derivative is easily prepared and can be isolated by affinity chromatography. Methylchymotrypsin retains unaltered its ability to bind specific substrates, but is essentially inactive. In spite of this loss of enzymatic activity, methylchymotrypsin forms strong complexes with several inhibitors. In addition, methylchymotrypsin which has been covalently linked to Sepharose is particularly useful for the isolation of protein inhibitors without the complications due to isolation of a mixture of partially cleaved forms of the inhibitor."} {"id": "PMID:163244", "title": "Interaction of flavins with electron-rich metals.", "content": "A complex of the electron-rich ion Cu(I) with the flavoquinone analogue 10-methylisoalloxazine has been synthesized and characterized by x-ray methods. The complex is unstable to oxygen. It is black-green in color, in contrast with the bright yellow, orange, or orange-brown crystalline complexes of 10-methylisoalloxazine or riboflavin with Cu(II), Ag(I), and Pb(II). These results are indicative of strong perturbation of the flavin electronic structure by the Cu(I) ion and suggest that this complex is a reasonable model for incipient transfer of an electron from a reduced metal to flavoquinone. the crystal structure is orthorhombic, Pna2-1, with unit cell constants a = 31.24(1) (figures in parentheses are estimated standard deviations), b = 12.862(4), c = 6.239(2) A, Pobs = 1.76 g per cm-3 and Pcalc = 1.77 g per cm-3 for Z = 4 and asymmetric formula CuClO4-2(C11H8N4O2). HCOOH. The final R factor based on 1250 counter-measured data is 8.8%. The 2 independent 10-methylisoalloxazine molecules, A and B, bind strongly to the cuprous ion throug N(5) of each flavin. The copper is approximately linearly coordinated with an N-Cu-N angle of 153(1) degrees, and Cu-N(5) distances of 1.94(2) A and 1.92(2) A. The next nearest atoms to Cu are the O(4) oxygens of each flavin, forming weak bonds with distances Cu-O(4) = 2.27(2) A and 2.21(2) A for molecules A and B. The dihedral angle between the 2 10-methylisoalloxazine molecules is 65.4 degrees.", "contents": "Interaction of flavins with electron-rich metals. A complex of the electron-rich ion Cu(I) with the flavoquinone analogue 10-methylisoalloxazine has been synthesized and characterized by x-ray methods. The complex is unstable to oxygen. It is black-green in color, in contrast with the bright yellow, orange, or orange-brown crystalline complexes of 10-methylisoalloxazine or riboflavin with Cu(II), Ag(I), and Pb(II). These results are indicative of strong perturbation of the flavin electronic structure by the Cu(I) ion and suggest that this complex is a reasonable model for incipient transfer of an electron from a reduced metal to flavoquinone. the crystal structure is orthorhombic, Pna2-1, with unit cell constants a = 31.24(1) (figures in parentheses are estimated standard deviations), b = 12.862(4), c = 6.239(2) A, Pobs = 1.76 g per cm-3 and Pcalc = 1.77 g per cm-3 for Z = 4 and asymmetric formula CuClO4-2(C11H8N4O2). HCOOH. The final R factor based on 1250 counter-measured data is 8.8%. The 2 independent 10-methylisoalloxazine molecules, A and B, bind strongly to the cuprous ion throug N(5) of each flavin. The copper is approximately linearly coordinated with an N-Cu-N angle of 153(1) degrees, and Cu-N(5) distances of 1.94(2) A and 1.92(2) A. The next nearest atoms to Cu are the O(4) oxygens of each flavin, forming weak bonds with distances Cu-O(4) = 2.27(2) A and 2.21(2) A for molecules A and B. The dihedral angle between the 2 10-methylisoalloxazine molecules is 65.4 degrees."} {"id": "PMID:163245", "title": "Structure of the active site of carbonic anhydrase as determined by electron spin resonance.", "content": "High resolution electron spin resonance spectra of the stepwise formation of CN- complexes of Co(II) and Cu(II) carbonic anhydrase show that both metal enzymes form successive 1:1 and 2:1 addition products with CN- at 112 K. The 1:1 complex with the Cu(II) enzyme has a rhombic ESR spectrum similar to the spectra of the 1:1 complexes of the Cu(II) enzyme with CH3COO-, OCN-, N3-, and SH-. The 1:1 complex with the CO(II) enzyme shows a broad resonance at 10 K indicating the presence of high spin Co(II). Previous optical, ESR, and magnetic susceptibility data suggest that the 1:1 complexes are 4-coordinate. At high concentrations of 13CN- the Cu(II) enzyme forms a 2:1 CN- complex with a shift to an axial ESR signal showing ligand nuclear superhyperfine structure from two magnetically equivalent equatorial nitrogen nuclei of the protein and two magnetically equivalent equatorial carbon ligands from two 13CN- anions. Under the same conditions a structurally analogous dicyanide complex of the co(II) enzyme forms with the appearance of and axial ESR signal typical of low spin Co(II). Ligand nuclear superhyperfine structure shows the presence of an axial protein nitrogen as ligand and two magnetically equivalent equatorial carbon ligands from two 13CN- anions. The dicyanide complexes of the Co(II) and Cu(II) enzymes form completely only in frozen solutions and analysis of the ESR spectra show them to have a 5-coordinate square pyrimidal geometry. Comparison of the ligand superhyperfine structure on the ESR signals of both dicyanide complexes shows that there are three nitrogen nuclei of the protein present as ligands at the metal binding site; one axial and two equatorial in the dicyanide complexes. A transient 5-coordinate intermediate might play a role in the mechanism of action of carbonic anhydrase by facilitating ligand exchange reactions within the inner coordination sphere of the Zn(II) ion at the active center.", "contents": "Structure of the active site of carbonic anhydrase as determined by electron spin resonance. High resolution electron spin resonance spectra of the stepwise formation of CN- complexes of Co(II) and Cu(II) carbonic anhydrase show that both metal enzymes form successive 1:1 and 2:1 addition products with CN- at 112 K. The 1:1 complex with the Cu(II) enzyme has a rhombic ESR spectrum similar to the spectra of the 1:1 complexes of the Cu(II) enzyme with CH3COO-, OCN-, N3-, and SH-. The 1:1 complex with the CO(II) enzyme shows a broad resonance at 10 K indicating the presence of high spin Co(II). Previous optical, ESR, and magnetic susceptibility data suggest that the 1:1 complexes are 4-coordinate. At high concentrations of 13CN- the Cu(II) enzyme forms a 2:1 CN- complex with a shift to an axial ESR signal showing ligand nuclear superhyperfine structure from two magnetically equivalent equatorial nitrogen nuclei of the protein and two magnetically equivalent equatorial carbon ligands from two 13CN- anions. Under the same conditions a structurally analogous dicyanide complex of the co(II) enzyme forms with the appearance of and axial ESR signal typical of low spin Co(II). Ligand nuclear superhyperfine structure shows the presence of an axial protein nitrogen as ligand and two magnetically equivalent equatorial carbon ligands from two 13CN- anions. The dicyanide complexes of the Co(II) and Cu(II) enzymes form completely only in frozen solutions and analysis of the ESR spectra show them to have a 5-coordinate square pyrimidal geometry. Comparison of the ligand superhyperfine structure on the ESR signals of both dicyanide complexes shows that there are three nitrogen nuclei of the protein present as ligands at the metal binding site; one axial and two equatorial in the dicyanide complexes. A transient 5-coordinate intermediate might play a role in the mechanism of action of carbonic anhydrase by facilitating ligand exchange reactions within the inner coordination sphere of the Zn(II) ion at the active center."} {"id": "PMID:163246", "title": "Refractoriness of cation transport in turkey erythrocytes to stimulation by cyclic adenosine 3':5'-monophosphate.", "content": "In turkey erythrocytes bidirectional fluxes of sodium and potassium develop a time-dependent refractoriness to stimulation by endogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP). The refractoriness of potassium influx and potassium outflux (both of which require extracellular sodium and potassium for stimulation by cyclic AMP) depends on the extracellular concentrations of sodium and potassium. In contrast, the refractoriness developed by sodium outflux (which does not require extracellular sodium or potassium for stimulation by cyclic AMP) does not depend on the extracellular concentrations of sodium or potassium. The refractoriness of these fluxes to cellular cyclic AMP reflects a decrease in the amount by which they can be maximally stimulated and appears to be proportional to the extent to which the transport system is utilized during the course of the incubation. Ouabain significantly reduces the rate at which cation transport in turkey erythrocytes becomes refractory to endogenous cyclic AMP. This effect of the glycoside is independent of the extracellular concentrations of sodium or potassium and does not correlate with how it alters the initial response of the transport systems to cyclic AMP.", "contents": "Refractoriness of cation transport in turkey erythrocytes to stimulation by cyclic adenosine 3':5'-monophosphate. In turkey erythrocytes bidirectional fluxes of sodium and potassium develop a time-dependent refractoriness to stimulation by endogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP). The refractoriness of potassium influx and potassium outflux (both of which require extracellular sodium and potassium for stimulation by cyclic AMP) depends on the extracellular concentrations of sodium and potassium. In contrast, the refractoriness developed by sodium outflux (which does not require extracellular sodium or potassium for stimulation by cyclic AMP) does not depend on the extracellular concentrations of sodium or potassium. The refractoriness of these fluxes to cellular cyclic AMP reflects a decrease in the amount by which they can be maximally stimulated and appears to be proportional to the extent to which the transport system is utilized during the course of the incubation. Ouabain significantly reduces the rate at which cation transport in turkey erythrocytes becomes refractory to endogenous cyclic AMP. This effect of the glycoside is independent of the extracellular concentrations of sodium or potassium and does not correlate with how it alters the initial response of the transport systems to cyclic AMP."} {"id": "PMID:163247", "title": "Adenylate cyclase system of bovine adrenal plasma membranes.", "content": "The adenylate cyclase system present in a preparation enriched in plasma membranes derived from bovine adrenal cortex was investigated in considerable detail. This system is stimulated by adrenocorticotropic hormone (ACTH), by biologically active analogs of this hormone, and by fluoride ion. The preparation contains sodium-potassium- and magnesium-dependent ATPases that are markedly inhibited by 50 mM sodium fluoride. Incorporation of a pyruvate phosphokinase ATP generating system into the adenylate cyclase assay medium provided constant substrate levels. In the presence of the ATP generating system, the rate of cyclic AMP formation (basal, fluoride, and ACTH-activated) was proportional to enzyme concentration and was linear with time. Proportionality with respect to enzyme concentration as concerned the hormone-activated adenylate cyclase was achieved only when the ratio of hormone to enzyme protein was kept constant. The temperature optimum of the adenylate cyclase, basal or activated, was approximately 30 degrees. Michaelis-Menten kinetics were observed when the ratio of Mg2+ to ATP was approximately 6:1. Both calcium and ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid completely inhibited the adenylate cyclase system at concentrations of 5 and 0.5 mM, respectively. GTP was inhibitory at concentrations of 10-2 M but had little effect at lower concentrations. Freezing in liquid nitrogen and storage at -60 degrees exerted little effect on the fluoride-stimulated enzyme but lowered hormone stimulated activity. Preincubation in the presence of ACTH afforded a high degree of stabilization of the enzyme system while preincubation with a biologically inactive analog afforded no protection.", "contents": "Adenylate cyclase system of bovine adrenal plasma membranes. The adenylate cyclase system present in a preparation enriched in plasma membranes derived from bovine adrenal cortex was investigated in considerable detail. This system is stimulated by adrenocorticotropic hormone (ACTH), by biologically active analogs of this hormone, and by fluoride ion. The preparation contains sodium-potassium- and magnesium-dependent ATPases that are markedly inhibited by 50 mM sodium fluoride. Incorporation of a pyruvate phosphokinase ATP generating system into the adenylate cyclase assay medium provided constant substrate levels. In the presence of the ATP generating system, the rate of cyclic AMP formation (basal, fluoride, and ACTH-activated) was proportional to enzyme concentration and was linear with time. Proportionality with respect to enzyme concentration as concerned the hormone-activated adenylate cyclase was achieved only when the ratio of hormone to enzyme protein was kept constant. The temperature optimum of the adenylate cyclase, basal or activated, was approximately 30 degrees. Michaelis-Menten kinetics were observed when the ratio of Mg2+ to ATP was approximately 6:1. Both calcium and ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid completely inhibited the adenylate cyclase system at concentrations of 5 and 0.5 mM, respectively. GTP was inhibitory at concentrations of 10-2 M but had little effect at lower concentrations. Freezing in liquid nitrogen and storage at -60 degrees exerted little effect on the fluoride-stimulated enzyme but lowered hormone stimulated activity. Preincubation in the presence of ACTH afforded a high degree of stabilization of the enzyme system while preincubation with a biologically inactive analog afforded no protection."} {"id": "PMID:163248", "title": "Cortisol binding in rat skeletal muscle.", "content": "Studies of the reversible binding of [3H]cortisol by rat gastrocnemius muscle cytoplasm in vitro reveal specific binding in the 27,000 times g supernatant fraction at 0 degrees. The [3H]cortisol-binding molecule had an apparant Kd value of 1.7 times 10-7 M and the number of binding sites was 0.99 pmol per mg of cytosol protein. Only a single class of [3H]cortisol-binding sites could be detected, whose protein nature was suggested by its susceptibility to nagarse. The [3H]cortisol-protein complex sedimented at similar to 4 S in a 5 to 20% sucrose gradient either in the presence or absence of 0.3 M KCl. Binding increased more than 2-fold in adrenalectomized rats and was markedly reduced in the muscle of rats pretreated with cortisol. In contrast to the binding of [3H]dexamethasone and [3H]triamcinolone acetonide to receptor proteins in muscle, no correlation was found between the ability of various steroids to complete wtth [3H]cortisol binding and their glucocorticoid potency: [3H]cortisol binding was inhibited by a 1000-fold higher concentration of unlabeled cortisol and progesterone but not by dexamethasone or triamcinolone acetonide. It is therefore suggested that the [3H]cortisol-binding reaction is not directly involved in the biological effects of all potent glucocorticoids in skeletal muscle. The [3H]cortisol-binding protein in muscle cytosol could not be unequivocally distinguished from rat plasma corticosteroid-binding globulin, because both had similar steroid specificity and temperature stability, were not markedly affected by--SH reagents, and displayed similar sedimentation properties.", "contents": "Cortisol binding in rat skeletal muscle. Studies of the reversible binding of [3H]cortisol by rat gastrocnemius muscle cytoplasm in vitro reveal specific binding in the 27,000 times g supernatant fraction at 0 degrees. The [3H]cortisol-binding molecule had an apparant Kd value of 1.7 times 10-7 M and the number of binding sites was 0.99 pmol per mg of cytosol protein. Only a single class of [3H]cortisol-binding sites could be detected, whose protein nature was suggested by its susceptibility to nagarse. The [3H]cortisol-protein complex sedimented at similar to 4 S in a 5 to 20% sucrose gradient either in the presence or absence of 0.3 M KCl. Binding increased more than 2-fold in adrenalectomized rats and was markedly reduced in the muscle of rats pretreated with cortisol. In contrast to the binding of [3H]dexamethasone and [3H]triamcinolone acetonide to receptor proteins in muscle, no correlation was found between the ability of various steroids to complete wtth [3H]cortisol binding and their glucocorticoid potency: [3H]cortisol binding was inhibited by a 1000-fold higher concentration of unlabeled cortisol and progesterone but not by dexamethasone or triamcinolone acetonide. It is therefore suggested that the [3H]cortisol-binding reaction is not directly involved in the biological effects of all potent glucocorticoids in skeletal muscle. The [3H]cortisol-binding protein in muscle cytosol could not be unequivocally distinguished from rat plasma corticosteroid-binding globulin, because both had similar steroid specificity and temperature stability, were not markedly affected by--SH reagents, and displayed similar sedimentation properties."} {"id": "PMID:163249", "title": "Purification and properties of stringent factor.", "content": "The stringent factor from Escherichia coli is the product of the relA locus. It is the enzyme that catalyzes the synthesis of pppGpp and ppGpp eliciting a pyrophosphate transfer from ATP to the 3'--OH of GTP (or GDP). This protein is responsible for the synthesis of pppGpp and ppGpp in stringent strains in response to an amino acid starvation. In vitro it catalyzes the synthesis of these guanosine compounds in either a ribosome-dependent reaction that requires a particular conformation of the ribosome i.e. the presence of an uncharged tRNA recognizing a codon in the acceptor (A) site of the ribosome or in a ribosome-independent reaction at temperatures under 30 degrees in the presence of only buffer, salts, and substrates. Here we report the purification of the stringent factor to near homogeneity. It is a monomeric protein with a molecular weight of 75,000. The properties of the ribosome-independent reaction are studied and it is shown that the presence of certain acidic proteins, such as the 50 S ribosomal proteins L7 and L12 or casein, or 20% methanol or both stimulates the reaction by creating an environment that together with the low temperature further stabilizes the stringent factor.", "contents": "Purification and properties of stringent factor. The stringent factor from Escherichia coli is the product of the relA locus. It is the enzyme that catalyzes the synthesis of pppGpp and ppGpp eliciting a pyrophosphate transfer from ATP to the 3'--OH of GTP (or GDP). This protein is responsible for the synthesis of pppGpp and ppGpp in stringent strains in response to an amino acid starvation. In vitro it catalyzes the synthesis of these guanosine compounds in either a ribosome-dependent reaction that requires a particular conformation of the ribosome i.e. the presence of an uncharged tRNA recognizing a codon in the acceptor (A) site of the ribosome or in a ribosome-independent reaction at temperatures under 30 degrees in the presence of only buffer, salts, and substrates. Here we report the purification of the stringent factor to near homogeneity. It is a monomeric protein with a molecular weight of 75,000. The properties of the ribosome-independent reaction are studied and it is shown that the presence of certain acidic proteins, such as the 50 S ribosomal proteins L7 and L12 or casein, or 20% methanol or both stimulates the reaction by creating an environment that together with the low temperature further stabilizes the stringent factor."} {"id": "PMID:163250", "title": "Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 (lambda). Activation by monovalent cations and an analysis of the effect of the adenosine triphosphate-magnesium ion complex on this activation process.", "content": "The dehydrogenase activity of the aspartokinase I-homoserine dehydrogenase I complex isolated from Escherichia coli K12 is subject to a cooperative activation by K+ or Rb+, which is characterized by a Hill coefficient of approximately 2. Ionic strength has little effect on the Hill coefficient for this activation process; however, high ionic strength appears to increase the enzyme's affinity for K+ and decrease its affinity for Rb+. The Vmax of the K+-activated dehydrogenase is greater than that of the Rb+-activated dehydrogenase. The results of a study of the competition between K+ and Rb+ in the activation process suggest the presence of an activated species containing both K+ and Rb+. The cooperative activation by K+ is antagonized by Na+ via a process that is noncooperative with respect to Na+. The MgATP-2- complex, a substrate for the kinase activity of aspartokinase I-homoserine dehydrogenase I, has a marked effect on the K+ activation of the dehydrogenase activity. Kinetic studies of this effect of MgATP-2- on the K+ requirement of the dehydrogenase at pH 8.9 indicate that: (a) activation by a monovalent cation is essential in the presence as well as in the absence of MgATP-2-; (b) the concentration of K+ required to activate fully the dehydrogenase is reduced in the presence of MgATP-2-; (c) activation of the dehydrogenase by K+ is noncooperative in the presence of MgATP-2-; and (d) the maximum velocity for the dehydrogenase catalyzed oxidation of homoserine is greater in the presence of MgATP-2- than in its absence. Based on these results, a simple model consistent with these data is proposed. Destruction of the kinase activity and the threonine sensitivity of the aspartokinase-homoserine dehydrogenase complex by treatment with 5,5'-dithiobis(2-nitrobenzoic acid) or by incubation at pH 9 also converts the K+ activation of the dehydrogenase from a cooperative to a noncooperative process. Marked protection of the enzyme against loss of threonine sensitivity at pH 9 is afforded by MgATP-2- plus K+ and homoserine. The apparent molecular radius of the enzyme complex as determined by gel filtration at pH 8.85 in the presence of threonine or MgATP-2- plus K+ and homoserine is dependent on the enzyme concentration. The observed apparent molecular radii of 70 A at high enzyme concentrations and 61 A at low enzyme concentrations are consistent with the enzyme's undergoing a concentration-dependent dissociation from a tetrameric to a dimeri", "contents": "Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 (lambda). Activation by monovalent cations and an analysis of the effect of the adenosine triphosphate-magnesium ion complex on this activation process. The dehydrogenase activity of the aspartokinase I-homoserine dehydrogenase I complex isolated from Escherichia coli K12 is subject to a cooperative activation by K+ or Rb+, which is characterized by a Hill coefficient of approximately 2. Ionic strength has little effect on the Hill coefficient for this activation process; however, high ionic strength appears to increase the enzyme's affinity for K+ and decrease its affinity for Rb+. The Vmax of the K+-activated dehydrogenase is greater than that of the Rb+-activated dehydrogenase. The results of a study of the competition between K+ and Rb+ in the activation process suggest the presence of an activated species containing both K+ and Rb+. The cooperative activation by K+ is antagonized by Na+ via a process that is noncooperative with respect to Na+. The MgATP-2- complex, a substrate for the kinase activity of aspartokinase I-homoserine dehydrogenase I, has a marked effect on the K+ activation of the dehydrogenase activity. Kinetic studies of this effect of MgATP-2- on the K+ requirement of the dehydrogenase at pH 8.9 indicate that: (a) activation by a monovalent cation is essential in the presence as well as in the absence of MgATP-2-; (b) the concentration of K+ required to activate fully the dehydrogenase is reduced in the presence of MgATP-2-; (c) activation of the dehydrogenase by K+ is noncooperative in the presence of MgATP-2-; and (d) the maximum velocity for the dehydrogenase catalyzed oxidation of homoserine is greater in the presence of MgATP-2- than in its absence. Based on these results, a simple model consistent with these data is proposed. Destruction of the kinase activity and the threonine sensitivity of the aspartokinase-homoserine dehydrogenase complex by treatment with 5,5'-dithiobis(2-nitrobenzoic acid) or by incubation at pH 9 also converts the K+ activation of the dehydrogenase from a cooperative to a noncooperative process. Marked protection of the enzyme against loss of threonine sensitivity at pH 9 is afforded by MgATP-2- plus K+ and homoserine. The apparent molecular radius of the enzyme complex as determined by gel filtration at pH 8.85 in the presence of threonine or MgATP-2- plus K+ and homoserine is dependent on the enzyme concentration. The observed apparent molecular radii of 70 A at high enzyme concentrations and 61 A at low enzyme concentrations are consistent with the enzyme's undergoing a concentration-dependent dissociation from a tetrameric to a dimeri"} {"id": "PMID:163251", "title": "Calcium-induced insulin release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187.", "content": "The role of Ca2+ on insulin release has been studied by the use of ionophore A23187. The ionophore complexes divalent cations and permits Ca2+ entry into cells by acting as a carrier in the plasma membranes. Cultured cells obtained by enzymatic digestion of pancreases from newborn rats were studied on the 3rd day of culture. With Ca2+ in the incubation medium the ionophore induced sustained insulin release even in the absence of glucose. Optimal effects of the ionophore were observed at 3 and 10 mug per ml in the presence of 0.3 to 1.0 mM Ca-2+. Under these conditions the insulin release was greater than that caused by 16.7 mM glucose. A graded response was observed to changes in Ca-2+ concentration from 0.1 to 1.0 mM Ca-2+. Higher Ca-2+ concentrations caused a large amount of insulin to be released promptly, but the release was not sustained. Mg-2+ and Sr-2+ were not found to substitute for Ca-2+. Ba-2+ at 0.3 mM stimulated insulin release even in the absence of ionophore. Cyclic adenosine 3':5'-monophosphate was able to increase ionophore-induced insulin release. The alpha-adrenergic effect of epinephrine to inhibit insulin release was not observed in the presence of Ca-2+ and the ionophore, and a stimulatory effect of epinephrine was seen. This unusual stimulatory effect of epinephrine was blocked by propranolol indicating a beta-adrenergic mechanism for epinephrine. It is concluded that Ca-2+, which plays an essential role in the stimulus-secretion coupling, can alone initiate and cause sustained insulin release.", "contents": "Calcium-induced insulin release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187. The role of Ca2+ on insulin release has been studied by the use of ionophore A23187. The ionophore complexes divalent cations and permits Ca2+ entry into cells by acting as a carrier in the plasma membranes. Cultured cells obtained by enzymatic digestion of pancreases from newborn rats were studied on the 3rd day of culture. With Ca2+ in the incubation medium the ionophore induced sustained insulin release even in the absence of glucose. Optimal effects of the ionophore were observed at 3 and 10 mug per ml in the presence of 0.3 to 1.0 mM Ca-2+. Under these conditions the insulin release was greater than that caused by 16.7 mM glucose. A graded response was observed to changes in Ca-2+ concentration from 0.1 to 1.0 mM Ca-2+. Higher Ca-2+ concentrations caused a large amount of insulin to be released promptly, but the release was not sustained. Mg-2+ and Sr-2+ were not found to substitute for Ca-2+. Ba-2+ at 0.3 mM stimulated insulin release even in the absence of ionophore. Cyclic adenosine 3':5'-monophosphate was able to increase ionophore-induced insulin release. The alpha-adrenergic effect of epinephrine to inhibit insulin release was not observed in the presence of Ca-2+ and the ionophore, and a stimulatory effect of epinephrine was seen. This unusual stimulatory effect of epinephrine was blocked by propranolol indicating a beta-adrenergic mechanism for epinephrine. It is concluded that Ca-2+, which plays an essential role in the stimulus-secretion coupling, can alone initiate and cause sustained insulin release."} {"id": "PMID:163252", "title": "Studies on cytochrome oxidase. Interactions of the cytochrome oxidase protein with phospholipids and cytochrome c.", "content": "1. By the application of the principle of the sequential fragmentation of the respiratory chain, a simple-method has been developed for the isolation of phospholipid-depleted and phospholipid-rich cytochrome oxidase preparations. 2. The phospholip-rich oxidase contains about 20% lipid, including mainly phosphatidylethanolamine, phosphatidylcholine, and cardiolipin. Its enzymic activity is not stimulated by an external lipid such as asolectin. 3. The phospholipid-depleted oxidase contains less than 0.1% lipid. It is enzymically inactive in catalyzing the oxidation of reduced cytochrome c by molecular oxygen. This activity can be fully restored by asolectin; and partially restored (approximately 75%) by purified phospholipids individually or in combination. The activity can be partially restored also by phospholipid mixtures isolated from mitochondria, from the oxidase itself, and from related preparations. Among the detergents tested only Emasol-1130 and Tween 80 show some stimulatory activity. 4. The phospholipid-depleted oxidase binds with cytochrome c evidently by \"protein-protein\" interactions as does the phospholipid-rich or the phospholipid-replenished oxidase to form a complex with the ratio of cytochrome c to heme a of unity. The complex prepared from phospholipid-depleted cytochrome oxidase exhibits a characteristic Soret absorption maximum at 415 nm in the difference spectrum of the carbon monoxide-reacted reduced form minus the reduced form. This 415-nm maximum is abolished by the replenishment of the complex with a phospholipid or by the dissociation of the complex in cholate or in a medium of high ionic strength. When ascorbate is used as an electron donor, the complex prepared from phospholipid-depleted cytochrome oxidase does not cause the reduction of cytochrome a3 which is in dramatic contrast to the complex from the phospholipid-rich or the phospholipid-replenished oxidase. However, dithionite reduces cytochrome a3 in all of the preparations of the cytochrome c-cytochrome oxidase complex. These facts suggest that the action of phospholipid on the electron transfer in cytochrome oxidase may be at the step between cytochromes a and a3. This conclusion is substantiated by preliminary kinetic results that the electron transfer from cytochrome a to a3 is much slower in the phospholipid-depleted than in phospholipid-rich or phospholipid-replenished oxidase. On the basis of the cytochrome c content, the enzymic activity has been found to be about 10 times higher in the system with the complex (in the presence of the replenishedhe external medium unless energy is provided, and that", "contents": "Studies on cytochrome oxidase. Interactions of the cytochrome oxidase protein with phospholipids and cytochrome c. 1. By the application of the principle of the sequential fragmentation of the respiratory chain, a simple-method has been developed for the isolation of phospholipid-depleted and phospholipid-rich cytochrome oxidase preparations. 2. The phospholip-rich oxidase contains about 20% lipid, including mainly phosphatidylethanolamine, phosphatidylcholine, and cardiolipin. Its enzymic activity is not stimulated by an external lipid such as asolectin. 3. The phospholipid-depleted oxidase contains less than 0.1% lipid. It is enzymically inactive in catalyzing the oxidation of reduced cytochrome c by molecular oxygen. This activity can be fully restored by asolectin; and partially restored (approximately 75%) by purified phospholipids individually or in combination. The activity can be partially restored also by phospholipid mixtures isolated from mitochondria, from the oxidase itself, and from related preparations. Among the detergents tested only Emasol-1130 and Tween 80 show some stimulatory activity. 4. The phospholipid-depleted oxidase binds with cytochrome c evidently by \"protein-protein\" interactions as does the phospholipid-rich or the phospholipid-replenished oxidase to form a complex with the ratio of cytochrome c to heme a of unity. The complex prepared from phospholipid-depleted cytochrome oxidase exhibits a characteristic Soret absorption maximum at 415 nm in the difference spectrum of the carbon monoxide-reacted reduced form minus the reduced form. This 415-nm maximum is abolished by the replenishment of the complex with a phospholipid or by the dissociation of the complex in cholate or in a medium of high ionic strength. When ascorbate is used as an electron donor, the complex prepared from phospholipid-depleted cytochrome oxidase does not cause the reduction of cytochrome a3 which is in dramatic contrast to the complex from the phospholipid-rich or the phospholipid-replenished oxidase. However, dithionite reduces cytochrome a3 in all of the preparations of the cytochrome c-cytochrome oxidase complex. These facts suggest that the action of phospholipid on the electron transfer in cytochrome oxidase may be at the step between cytochromes a and a3. This conclusion is substantiated by preliminary kinetic results that the electron transfer from cytochrome a to a3 is much slower in the phospholipid-depleted than in phospholipid-rich or phospholipid-replenished oxidase. On the basis of the cytochrome c content, the enzymic activity has been found to be about 10 times higher in the system with the complex (in the presence of the replenishedhe external medium unless energy is provided, and that"} {"id": "PMID:163253", "title": "Radiolabeling of proteins and viruses in vitro by acetylation with radioactive acetic anhydride.", "content": "We describe a convenient, rapid, and reproducible method for labeling proteins in vitro by acetylation with [3H] or [14-C]acetic anhydride dissolved in small amounts of anhydrous dioxane. The reaction is carried out at neutral pH and does not require the use of detergents, water-immiscible organic solvents, oxidizing, or reducing agents. Thus undesirable solvent-induced alterations in protein structure and biological activity are minimized. A method for calculating the specific activity of the protein and the efficiency of acetylation at known concentrations of protein and acetic anhydride is presented. Radioacetylated proteins were shown to be suitable for use as molecular weight calibration standards and as protein markers in polyacrylamide gel electrophoresis, gel filtration, and enzyme studies. Acetic anhydride was used to label intact oncornaviruses, which consist of a complex ribonucleo-protein core within a lipid envelope. Some of the viral lipid and all of the viral proteins, including the internal ones, were labeled without detectable alterations in viral morphology or buoyant density. This result suggests that acetic anhydride, evidently by virtue of its small size and neutral charge, penetrates freely throughout the viral membrane and core structures. The reactivity of RNA with acetic anhydride was less than 1% that of protein under similar reaction conditions.", "contents": "Radiolabeling of proteins and viruses in vitro by acetylation with radioactive acetic anhydride. We describe a convenient, rapid, and reproducible method for labeling proteins in vitro by acetylation with [3H] or [14-C]acetic anhydride dissolved in small amounts of anhydrous dioxane. The reaction is carried out at neutral pH and does not require the use of detergents, water-immiscible organic solvents, oxidizing, or reducing agents. Thus undesirable solvent-induced alterations in protein structure and biological activity are minimized. A method for calculating the specific activity of the protein and the efficiency of acetylation at known concentrations of protein and acetic anhydride is presented. Radioacetylated proteins were shown to be suitable for use as molecular weight calibration standards and as protein markers in polyacrylamide gel electrophoresis, gel filtration, and enzyme studies. Acetic anhydride was used to label intact oncornaviruses, which consist of a complex ribonucleo-protein core within a lipid envelope. Some of the viral lipid and all of the viral proteins, including the internal ones, were labeled without detectable alterations in viral morphology or buoyant density. This result suggests that acetic anhydride, evidently by virtue of its small size and neutral charge, penetrates freely throughout the viral membrane and core structures. The reactivity of RNA with acetic anhydride was less than 1% that of protein under similar reaction conditions."} {"id": "PMID:163254", "title": "Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine.", "content": "Specific binding of 1alpha,25-dihydroxycholecalciferol to macromolecular components of small intestinal mucosa nuclei is demonstrated in vitamin D-deficient chicks. The nuclear 1alpha,25-dihydroxycholecalciferol-macromolecule complex was isolated on sucrose density gradients and sediments at 3.7 S in the presence of 0.3 M KCl. Agarose gel filtration of the nuclear component indicated an apparent molecular weight of 47,000. The nuclear receptor complexes could not be distinguished from previously described cytoplasmic 1alpha,25-dihydroxycholecalciferol-binding components by the ultracentrifugation and chromatographic procedures employed. The association of the 3-H-sterol with the nuclear component is thermolabile and is destroyed by treatment with pronase, but not by nucleases; the receptor component is therefore presumed to be a protein. The macromolecular-1alpha,25-dihydroxycholecalciferol complex formed in vivo or in vitro at 25 degrees can be extracted from intestinal nuclei by 0.3 M KCl, but not by low salt buffers. Smaller amounts of the 3.7 S binding component can be detected in isolated purified chromatin or after incubation of 1alpha,25-dihydroxy[3-H]cholecalciferol with reconstituted cytosol-chromatin at 0 degrees. Following incubation of the labeled hormone with reconstituted cytosol-chromatin at 0 degrees, 1alpha,25-dihydroxy[3-H]cholecalciferol is primarily associated with the cytoplasmic receptor, After shifting the incubation temperature to 25 degrees, a progressive increase in the concentration of the nuclear receptor complex and a concomitant decrease in the concentration of the cytoplasmic binding component occur. Thus the 1alpha,25-dihydroxycholecalciferol binding molecules appear to exist primarily in the cytoplasm, where they presumably function to transport the hormone into the nucleus. Experiments employing incubation of 1alpha,25-dihydroxy[3-H]cholecalciferol with reconstituted cytosol-chromatin from nontarget tissues indicate a requirement for both intestinal cytosol and chromatin for maximal formation of the nuclear hormone-receptor complex. These results suggest that the nuclear-binding component arises from hormone-dependent transfer of the cytoplasmic 1alpha,25-dihydroxycholecalciferol receptor to intestinal chromatin acceptor sites.", "contents": "Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine. Specific binding of 1alpha,25-dihydroxycholecalciferol to macromolecular components of small intestinal mucosa nuclei is demonstrated in vitamin D-deficient chicks. The nuclear 1alpha,25-dihydroxycholecalciferol-macromolecule complex was isolated on sucrose density gradients and sediments at 3.7 S in the presence of 0.3 M KCl. Agarose gel filtration of the nuclear component indicated an apparent molecular weight of 47,000. The nuclear receptor complexes could not be distinguished from previously described cytoplasmic 1alpha,25-dihydroxycholecalciferol-binding components by the ultracentrifugation and chromatographic procedures employed. The association of the 3-H-sterol with the nuclear component is thermolabile and is destroyed by treatment with pronase, but not by nucleases; the receptor component is therefore presumed to be a protein. The macromolecular-1alpha,25-dihydroxycholecalciferol complex formed in vivo or in vitro at 25 degrees can be extracted from intestinal nuclei by 0.3 M KCl, but not by low salt buffers. Smaller amounts of the 3.7 S binding component can be detected in isolated purified chromatin or after incubation of 1alpha,25-dihydroxy[3-H]cholecalciferol with reconstituted cytosol-chromatin at 0 degrees. Following incubation of the labeled hormone with reconstituted cytosol-chromatin at 0 degrees, 1alpha,25-dihydroxy[3-H]cholecalciferol is primarily associated with the cytoplasmic receptor, After shifting the incubation temperature to 25 degrees, a progressive increase in the concentration of the nuclear receptor complex and a concomitant decrease in the concentration of the cytoplasmic binding component occur. Thus the 1alpha,25-dihydroxycholecalciferol binding molecules appear to exist primarily in the cytoplasm, where they presumably function to transport the hormone into the nucleus. Experiments employing incubation of 1alpha,25-dihydroxy[3-H]cholecalciferol with reconstituted cytosol-chromatin from nontarget tissues indicate a requirement for both intestinal cytosol and chromatin for maximal formation of the nuclear hormone-receptor complex. These results suggest that the nuclear-binding component arises from hormone-dependent transfer of the cytoplasmic 1alpha,25-dihydroxycholecalciferol receptor to intestinal chromatin acceptor sites."} {"id": "PMID:163255", "title": "Interactions of adrenocorticotropic hormone with its adrenal receptors. Degradation of ACTH-1-24 and ACTH-11-24.", "content": "Crude membranes (20,000 times g pellet) prepared from human, rat, and ovine adrenals bind 125-I-corticotropin-(1-24)-tetracosapeptide (125-I-ACTH-1-24) and degrade unbound hormone. The degradation is dependent on temperature and the concentration of membrane proteins. The degradation of 125-I-[9-tryptophan(o-nitrophenylsulfenyl)]-corticotropin-(1-24)-tetracosapeptide (125-I-NPS-ACTH-1-24) is similar to 125-I-ACTH-1-24, but that of 125-I-corticotropin-(11-24)-tetradecapeptide (125-I-ACTH-1-24 is inhibited by ACTH-1-24 and corticotropin-(1-10)-decapeptide (ACTH-1-10), but ACTH-11-24 at the same molar concentration has no effect. On the other hand, the degradation of 125-I-ACTH-11-24 is protected by ACTH-11-24 and ACTH-1-24, but not by ACTH-1-10. This suggests two systems of degradation, one will have the NH-2-terminal sequence of ACTH-1-24 as substrate, and the other the 11-24 COOH-terminal sequence. The main label product from the degradation of the 125-I-ACTH-1-24 and 125-I-ACTH-11-24 behaves as [125-I]monoiodotyrosine on Sephadex G-50 and paper chromatography. The independence of ACTH binding to its receptor and degradation is demonstrated by the following facts. (a) Calcium and pancreatic trypsin inhibitor completely inhibit the binding at concentrations when the degradation is not altered; (b) the sequences of peptides of ACTH which inhibit the binding and degradation of 125-I-ACTH-1-24 are different.", "contents": "Interactions of adrenocorticotropic hormone with its adrenal receptors. Degradation of ACTH-1-24 and ACTH-11-24. Crude membranes (20,000 times g pellet) prepared from human, rat, and ovine adrenals bind 125-I-corticotropin-(1-24)-tetracosapeptide (125-I-ACTH-1-24) and degrade unbound hormone. The degradation is dependent on temperature and the concentration of membrane proteins. The degradation of 125-I-[9-tryptophan(o-nitrophenylsulfenyl)]-corticotropin-(1-24)-tetracosapeptide (125-I-NPS-ACTH-1-24) is similar to 125-I-ACTH-1-24, but that of 125-I-corticotropin-(11-24)-tetradecapeptide (125-I-ACTH-1-24 is inhibited by ACTH-1-24 and corticotropin-(1-10)-decapeptide (ACTH-1-10), but ACTH-11-24 at the same molar concentration has no effect. On the other hand, the degradation of 125-I-ACTH-11-24 is protected by ACTH-11-24 and ACTH-1-24, but not by ACTH-1-10. This suggests two systems of degradation, one will have the NH-2-terminal sequence of ACTH-1-24 as substrate, and the other the 11-24 COOH-terminal sequence. The main label product from the degradation of the 125-I-ACTH-1-24 and 125-I-ACTH-11-24 behaves as [125-I]monoiodotyrosine on Sephadex G-50 and paper chromatography. The independence of ACTH binding to its receptor and degradation is demonstrated by the following facts. (a) Calcium and pancreatic trypsin inhibitor completely inhibit the binding at concentrations when the degradation is not altered; (b) the sequences of peptides of ACTH which inhibit the binding and degradation of 125-I-ACTH-1-24 are different."} {"id": "PMID:163256", "title": "Covalent binding of 3-pyridinealdehyde nicotinamide adenine dinucleotide and substrate to glyceraldehyde 3-phosphate dehydrogenase.", "content": "Glyceraldehyde 3-phosphate dehydrogenase (D-glyceraldehyde-3-phoshate:nicotinamide adenine dinucleotide oxidoreductase (phosphorylating), EC 1.2.1.12) forms a complex with 3-pyridinealdehyde-NAD which survives precipitation with 7% perchloric acid. The molar ratio bound 3-pyridinealdehyde-NAD to the enzyme is 2.5 to 2.9. Lactate, malate, and alcohol dehydrogenases do not form acid-precipitable complexes with 3-pyridinealdehyde-NAD. 3-Pyridinealdehyde-deamino-NAD or glyceraldehyde 3-phosphate also forms an acid-stable complex with glyceraldehyde 3-phosphate dehydrogenase; however, NAD, 3-acetylpyridine-NAD, or thionicotinamide-NAD does not produce an acid-stable complex. Incubation of the glyceraldehyde 3-phosphate dehydrogenase with glyceraldehyde 3-phosphate, acetyl phosphate, iodoacetic acid, or iodosobenzoate inhibits the formation of the acid-stable complex with 3-pyridinealdehyde-NAD. Glyceraldehyde 3-phosphate or 3-pyridinealdehyde-NAD also prevents carboxymethylation of the active site cysteine-149 by[14-C]iodoacetic acid. These studies indicate that the aldehyde group of 3-pyridinealdehyde-NAD forms a thiohemiacetal linkage with cysteine-149 which is the substrate binding site for the dehydrogenase reaction. These findings may account for the fact that 3-pyridinealdehyde-NAD strongly inhibits the dehydrogenase and esterase activities of 3-pyridinealdehyde-NAD forms a thiohemiacetal linkage with cysteine-149 which is the substrate binding site for the dehydrogenase reaction. These findings may account for the fact that 3-pyridinealdehyde-NAD strongly inhibits the dehydrogenase and esterase activities of glyceraldehyde 3-phosphate dehydrogenase which require reduced cysteine-149. However, the analogue does not inhibit the acetyl phosphates activity of the enzyme for which the active site sulfhydryl residues must be oxidized.", "contents": "Covalent binding of 3-pyridinealdehyde nicotinamide adenine dinucleotide and substrate to glyceraldehyde 3-phosphate dehydrogenase. Glyceraldehyde 3-phosphate dehydrogenase (D-glyceraldehyde-3-phoshate:nicotinamide adenine dinucleotide oxidoreductase (phosphorylating), EC 1.2.1.12) forms a complex with 3-pyridinealdehyde-NAD which survives precipitation with 7% perchloric acid. The molar ratio bound 3-pyridinealdehyde-NAD to the enzyme is 2.5 to 2.9. Lactate, malate, and alcohol dehydrogenases do not form acid-precipitable complexes with 3-pyridinealdehyde-NAD. 3-Pyridinealdehyde-deamino-NAD or glyceraldehyde 3-phosphate also forms an acid-stable complex with glyceraldehyde 3-phosphate dehydrogenase; however, NAD, 3-acetylpyridine-NAD, or thionicotinamide-NAD does not produce an acid-stable complex. Incubation of the glyceraldehyde 3-phosphate dehydrogenase with glyceraldehyde 3-phosphate, acetyl phosphate, iodoacetic acid, or iodosobenzoate inhibits the formation of the acid-stable complex with 3-pyridinealdehyde-NAD. Glyceraldehyde 3-phosphate or 3-pyridinealdehyde-NAD also prevents carboxymethylation of the active site cysteine-149 by[14-C]iodoacetic acid. These studies indicate that the aldehyde group of 3-pyridinealdehyde-NAD forms a thiohemiacetal linkage with cysteine-149 which is the substrate binding site for the dehydrogenase reaction. These findings may account for the fact that 3-pyridinealdehyde-NAD strongly inhibits the dehydrogenase and esterase activities of 3-pyridinealdehyde-NAD forms a thiohemiacetal linkage with cysteine-149 which is the substrate binding site for the dehydrogenase reaction. These findings may account for the fact that 3-pyridinealdehyde-NAD strongly inhibits the dehydrogenase and esterase activities of glyceraldehyde 3-phosphate dehydrogenase which require reduced cysteine-149. However, the analogue does not inhibit the acetyl phosphates activity of the enzyme for which the active site sulfhydryl residues must be oxidized."} {"id": "PMID:163257", "title": "4-Nitrocatechol as a colorimetric probe for non-heme iron dioxygenases.", "content": "4-Nitrocatechol is examined as an active site probe for non-heme iron dioxygenases and found to be of value, particularly with those containing iron in the Fe(II) oxidation state. 4-Nitrocatechol is astrong competitive inhibitor of substrate oxygenation by protocatechuate 3,4-dioxygenase, forming a reversible complex with this enzyme, and by pyrocatechase. The number of binding sites per enzyme molecule titrated spectrophotometrically with 4-nitrocatechol agrees with results from previous studies with either the principal substrate or other analogues, as expected of an effective probe. Despite these facts and the observation that both enzymes cleave the same substrates at the same carbon-carbon bond, the optical and electron paramagnetic resonance (EPR) spectra of their 4-nitrocatechol complexes are remarkably different. The 4-nitocatechol-protocatechuate 3,4-dioxygenase optical spectra resemble that of the 4-nitrocatecholate ion shifted 20 to 30 nm to longer wavelength. Concomitant with this change the EPR signal centered at g equal 4.28 shows increased rhombicity (g values at 4.74, 4.28, and 3.74). In contrast, the spectrum of the 4-nitrocatechol-pyrocatechase complex has a maximum at the same wavelength as that of a 1:1 solution of free Fe(II) and 4-nitrocatechol in the absence of enzyme after titration of the catecholic protons with base and the g equal 4.28 EPR signal is not resolved at liquid N-2 temperature. These changes are interpreted as resulting in part from a pronounced change in the ligand fields about the irons at the active sites which in the case of protocatechuate 3,4-dioxygenase leads to enzyme inactivation. The results also are the first indication that substrate analogues change their ionization form upon complexation with Fe (III) dioxygenases. The interaction of the probe with metapyrocatechase, an Fe(III) containing dioxygenase, and with several additional oxygenases and hydroperoxidases is also briefly examined. The probe is not specific for any particular class of non-heme iron dioxygenases.", "contents": "4-Nitrocatechol as a colorimetric probe for non-heme iron dioxygenases. 4-Nitrocatechol is examined as an active site probe for non-heme iron dioxygenases and found to be of value, particularly with those containing iron in the Fe(II) oxidation state. 4-Nitrocatechol is astrong competitive inhibitor of substrate oxygenation by protocatechuate 3,4-dioxygenase, forming a reversible complex with this enzyme, and by pyrocatechase. The number of binding sites per enzyme molecule titrated spectrophotometrically with 4-nitrocatechol agrees with results from previous studies with either the principal substrate or other analogues, as expected of an effective probe. Despite these facts and the observation that both enzymes cleave the same substrates at the same carbon-carbon bond, the optical and electron paramagnetic resonance (EPR) spectra of their 4-nitrocatechol complexes are remarkably different. The 4-nitocatechol-protocatechuate 3,4-dioxygenase optical spectra resemble that of the 4-nitrocatecholate ion shifted 20 to 30 nm to longer wavelength. Concomitant with this change the EPR signal centered at g equal 4.28 shows increased rhombicity (g values at 4.74, 4.28, and 3.74). In contrast, the spectrum of the 4-nitrocatechol-pyrocatechase complex has a maximum at the same wavelength as that of a 1:1 solution of free Fe(II) and 4-nitrocatechol in the absence of enzyme after titration of the catecholic protons with base and the g equal 4.28 EPR signal is not resolved at liquid N-2 temperature. These changes are interpreted as resulting in part from a pronounced change in the ligand fields about the irons at the active sites which in the case of protocatechuate 3,4-dioxygenase leads to enzyme inactivation. The results also are the first indication that substrate analogues change their ionization form upon complexation with Fe (III) dioxygenases. The interaction of the probe with metapyrocatechase, an Fe(III) containing dioxygenase, and with several additional oxygenases and hydroperoxidases is also briefly examined. The probe is not specific for any particular class of non-heme iron dioxygenases."} {"id": "PMID:163258", "title": "Electron microscopic studies of proteoglycan aggregates from bovine articular cartilage.", "content": "Proteoglycan aggregates from bovine articular cartilage have been visualized by electron microscopy of mixed proteoglycan-cytochrome c monolayers. The proteoglycan aggregates consist of proteoglycan subunits arising laterally at fairly regular intervals (20 to 30 nm) from the opposite sides of an elongated filamentous structure. The filamentous backbone in individual aggregates varies in length from 400 to 4000 nm. The individual proteoglycan subunits in the aggregate vary in length from 100 to 400 nm. However, there is no difference in the average size of the proteoglycan subunits associated with the largest or smallest aggregates. The sizes of the individual aggregates are determined mainly by the lengths of their filamentous backbones. The stoichiometry of binding of subunits to filament, calculated from the data reported here, is close to that for the binding of subunits to hyaluronic acid reported by others.", "contents": "Electron microscopic studies of proteoglycan aggregates from bovine articular cartilage. Proteoglycan aggregates from bovine articular cartilage have been visualized by electron microscopy of mixed proteoglycan-cytochrome c monolayers. The proteoglycan aggregates consist of proteoglycan subunits arising laterally at fairly regular intervals (20 to 30 nm) from the opposite sides of an elongated filamentous structure. The filamentous backbone in individual aggregates varies in length from 400 to 4000 nm. The individual proteoglycan subunits in the aggregate vary in length from 100 to 400 nm. However, there is no difference in the average size of the proteoglycan subunits associated with the largest or smallest aggregates. The sizes of the individual aggregates are determined mainly by the lengths of their filamentous backbones. The stoichiometry of binding of subunits to filament, calculated from the data reported here, is close to that for the binding of subunits to hyaluronic acid reported by others."} {"id": "PMID:163259", "title": "Structural determination of the sialic acid polysaccharide antigens of Neisseria meningitidis serogroups B and C with carbon 13 nuclear magnetic resonance.", "content": "The application of 13-C nuclear magnetic resonance to the analysis of some sialic acid-containing meningococcal polysaccharide antigens is described. Complete assignments of the spectra of both the native serogroup B and the de-O-acetylated serogroup C polysaccharides have been made. These assignments were based on the corresponding data for some related monomers (sialic acid and its alpha-and beta-methylglycosides) and on supportive chemical evidence. The data indicate that the serogroup B polysaccharide is a 2 yields 8-alpha-linked homopolymer of sialic acid, identical in structure with colominic acid from Escherichia coli, whereas the de-O-acetylated serogroup C polysaccharide is a 2 yield 9-alpha-linked homopolymer. The native serogroup C polysaccharide is O-acetylated (1.16 mol of O-acetyl per sialic acid residue), all the O-acetyl substituents being located only at C-7 and C-8 of the sialic acid residues, and in addition contains unacetylated residues (24%). The polysaccharide contains di-O-acetylated residues (O-acetyl on C-7 and C-8), and at least one of the possible monoacetylated residues at C-7 or C-8.", "contents": "Structural determination of the sialic acid polysaccharide antigens of Neisseria meningitidis serogroups B and C with carbon 13 nuclear magnetic resonance. The application of 13-C nuclear magnetic resonance to the analysis of some sialic acid-containing meningococcal polysaccharide antigens is described. Complete assignments of the spectra of both the native serogroup B and the de-O-acetylated serogroup C polysaccharides have been made. These assignments were based on the corresponding data for some related monomers (sialic acid and its alpha-and beta-methylglycosides) and on supportive chemical evidence. The data indicate that the serogroup B polysaccharide is a 2 yields 8-alpha-linked homopolymer of sialic acid, identical in structure with colominic acid from Escherichia coli, whereas the de-O-acetylated serogroup C polysaccharide is a 2 yield 9-alpha-linked homopolymer. The native serogroup C polysaccharide is O-acetylated (1.16 mol of O-acetyl per sialic acid residue), all the O-acetyl substituents being located only at C-7 and C-8 of the sialic acid residues, and in addition contains unacetylated residues (24%). The polysaccharide contains di-O-acetylated residues (O-acetyl on C-7 and C-8), and at least one of the possible monoacetylated residues at C-7 or C-8."} {"id": "PMID:163260", "title": "Labeling of soybean agglutinin by oxidation with sodium periodate followed by reduction with sodium [3-H]borohydride.", "content": "Periodate oxidation of soybean agglutinin, a glycoprotein lectin, resulted in destruction of up to 5 out of the 9 mannose residues present in each of its subunits (MW 30,000) without any loss of hemagglutinating activity. The oxidation did, however, abolish the interaction of soybean agglutinin with concanvalin A, as measured by quantitative precipitation. Reduction with sodium [3-H]borohydride of soybean agglutinin in which 4 out of 9 mannose residues per subunit were oxidized, afforded a radioactive product which retained full hemagglutinating activity and was indistinguishable from the native lectin by gel filtration, gel electrophoresis, and affinity chromatography. These results establish that the integrity of the carbohydrate side chain of soybean agglutinin is not essential for the biological activity of the lectin, and suggest a general method for the preparation of radioactive glycoprotein lectins.", "contents": "Labeling of soybean agglutinin by oxidation with sodium periodate followed by reduction with sodium [3-H]borohydride. Periodate oxidation of soybean agglutinin, a glycoprotein lectin, resulted in destruction of up to 5 out of the 9 mannose residues present in each of its subunits (MW 30,000) without any loss of hemagglutinating activity. The oxidation did, however, abolish the interaction of soybean agglutinin with concanvalin A, as measured by quantitative precipitation. Reduction with sodium [3-H]borohydride of soybean agglutinin in which 4 out of 9 mannose residues per subunit were oxidized, afforded a radioactive product which retained full hemagglutinating activity and was indistinguishable from the native lectin by gel filtration, gel electrophoresis, and affinity chromatography. These results establish that the integrity of the carbohydrate side chain of soybean agglutinin is not essential for the biological activity of the lectin, and suggest a general method for the preparation of radioactive glycoprotein lectins."} {"id": "PMID:163266", "title": "Lipid composition of bovine serum lipoproteins.", "content": "The four classes of lipoproteins (one of very low density, two of low density, and one of high density) were isolated from the serum of a lactating Friesian cow. The proportions of protein and of the different lipid classes were determined in each lipoprotein. Triglycerides predominated in the very low density lipoprotein, and cholesteryl esters and phospholipids in the others. The triglycerides of the very low density lipoprotein were richer in oleic acid than were those of the low density lipoproteins, but its cholesteryl esters were relatively poorer in linoleic and linolenic acid than were those of any of the others. Phytanic acid (3, 7, 11, 15-tetramethylhexadecan-1-oic acid) was in all lipoproteins except those of very low density; it was not in cholesteryl esters but was abundant in triglycerides, particularly in those of the low density lipoproteins. Hydrolysis of the triglycerides of very low density lipoprotein with pancreatic lipase showed that 82% of their stearic acid was esterified to the 1- and 3-positions of glycerol and that 64% of their palmitic acid was esterified to the 2-position.", "contents": "Lipid composition of bovine serum lipoproteins. The four classes of lipoproteins (one of very low density, two of low density, and one of high density) were isolated from the serum of a lactating Friesian cow. The proportions of protein and of the different lipid classes were determined in each lipoprotein. Triglycerides predominated in the very low density lipoprotein, and cholesteryl esters and phospholipids in the others. The triglycerides of the very low density lipoprotein were richer in oleic acid than were those of the low density lipoproteins, but its cholesteryl esters were relatively poorer in linoleic and linolenic acid than were those of any of the others. Phytanic acid (3, 7, 11, 15-tetramethylhexadecan-1-oic acid) was in all lipoproteins except those of very low density; it was not in cholesteryl esters but was abundant in triglycerides, particularly in those of the low density lipoproteins. Hydrolysis of the triglycerides of very low density lipoprotein with pancreatic lipase showed that 82% of their stearic acid was esterified to the 1- and 3-positions of glycerol and that 64% of their palmitic acid was esterified to the 2-position."} {"id": "PMID:163274", "title": "The use of the haemagglutination-inhibition test for detecting antibodies to type SAT 2 foot-and-mouth disease viruses in cattle sera.", "content": "Two strains of type SAT 2-foot-and-mouth disease virus which gave high titres of haemagglutinin activity reacted type-specifically in direct haemagglutination-inhibition tests with reference, bovine convalescent antisera. Comparisons of the haemagglutination-inhibition and the serum neutralization tests using cattle sera showed that both were equally specific and sensitive for detecting virus antibody.", "contents": "The use of the haemagglutination-inhibition test for detecting antibodies to type SAT 2 foot-and-mouth disease viruses in cattle sera. Two strains of type SAT 2-foot-and-mouth disease virus which gave high titres of haemagglutinin activity reacted type-specifically in direct haemagglutination-inhibition tests with reference, bovine convalescent antisera. Comparisons of the haemagglutination-inhibition and the serum neutralization tests using cattle sera showed that both were equally specific and sensitive for detecting virus antibody."} {"id": "PMID:163275", "title": "The effects of humoral, cellular and non-specific immunity on intracerebral Bordetella pertussis infections in mice.", "content": "When mice were injected intracerebrally with doses of Bordetella pertussis vaccine greater than 5 ImD 50 and challenged intracerebrally 14 days later with virulent B. pertussis there was an immediate reduction in the numbers of organisms. An analysis of this in vivo bactericidal effect has shown that large doses of an unrelated vaccine, Salmonella typhosa, equivalent in cell mass to about 50 ImD 50 of B. pertussis vaccine can achieve this effect, so for such doses the effect must be partly non-specific. This action is not maintained and so is not ultimately protective. Local immunoglobulin was also demonstrable 14 days after 300 ImD 50 of B. pertussis vaccine but following smaller doses of 10-20 ImD 50 it could not be found until after the mice had been infected and the blood-brain barrier impaired. A similar immediate reduction in the numbers of infecting organisms inoculated 1 day after vaccination has been shown to follow very small, non-protective doses of vaccines unrelated to B. pertussis and to be achieved with lipopolysaccharide and endotoxin isolated from B. pertussis. Brains were not sterilized and only in mice receiving protective B. pertussis vaccine was the lowering of infection maintained beyond 2 days and the brains eventually sterilized. The antibody passively protecting mice against intracerebral infection was found in the 19S and 11 S globulin fractions of the serum of once-vaccinated mice and in the 11 S and 7 S fractions of the serum of rabbits and ascitic fluid of mice receiving repeated doses of vaccine. The IgM probably eliminated infections by immediate sterilization but had to be present locally to do so since it was unable to pass from the circulation into the brain, and was therefore inactive when injected intraperitoneally. The IgA and IgG were not so restricted and both the 11 S and 7 S globulins were capable of exerting an immediate suppressive effect on infecting organisms. The 7 S globulin was also capable of a maintained or delayed suppressive effect. Lymphocytes from fully protected once-vaccinated mice, transferred 2-3 weeks after intraperitoneal vaccination, were able to confer some protection when injected intraperitoneally or intracerebrally into recipient mice infected 2 weeks after transfer. Homologous, non-concentrated antiserum from once-vaccinated mice, injected intraperitoneally 1 hr. before infection sometimes augmented the transferred immunity, whereas alone it was inactive.", "contents": "The effects of humoral, cellular and non-specific immunity on intracerebral Bordetella pertussis infections in mice. When mice were injected intracerebrally with doses of Bordetella pertussis vaccine greater than 5 ImD 50 and challenged intracerebrally 14 days later with virulent B. pertussis there was an immediate reduction in the numbers of organisms. An analysis of this in vivo bactericidal effect has shown that large doses of an unrelated vaccine, Salmonella typhosa, equivalent in cell mass to about 50 ImD 50 of B. pertussis vaccine can achieve this effect, so for such doses the effect must be partly non-specific. This action is not maintained and so is not ultimately protective. Local immunoglobulin was also demonstrable 14 days after 300 ImD 50 of B. pertussis vaccine but following smaller doses of 10-20 ImD 50 it could not be found until after the mice had been infected and the blood-brain barrier impaired. A similar immediate reduction in the numbers of infecting organisms inoculated 1 day after vaccination has been shown to follow very small, non-protective doses of vaccines unrelated to B. pertussis and to be achieved with lipopolysaccharide and endotoxin isolated from B. pertussis. Brains were not sterilized and only in mice receiving protective B. pertussis vaccine was the lowering of infection maintained beyond 2 days and the brains eventually sterilized. The antibody passively protecting mice against intracerebral infection was found in the 19S and 11 S globulin fractions of the serum of once-vaccinated mice and in the 11 S and 7 S fractions of the serum of rabbits and ascitic fluid of mice receiving repeated doses of vaccine. The IgM probably eliminated infections by immediate sterilization but had to be present locally to do so since it was unable to pass from the circulation into the brain, and was therefore inactive when injected intraperitoneally. The IgA and IgG were not so restricted and both the 11 S and 7 S globulins were capable of exerting an immediate suppressive effect on infecting organisms. The 7 S globulin was also capable of a maintained or delayed suppressive effect. Lymphocytes from fully protected once-vaccinated mice, transferred 2-3 weeks after intraperitoneal vaccination, were able to confer some protection when injected intraperitoneally or intracerebrally into recipient mice infected 2 weeks after transfer. Homologous, non-concentrated antiserum from once-vaccinated mice, injected intraperitoneally 1 hr. before infection sometimes augmented the transferred immunity, whereas alone it was inactive."} {"id": "PMID:163276", "title": "In vitro detection of immune responses to MTV-induced mammary tumors: qualitative differences in response detected by time studies.", "content": "Both BALB/cfC3H females neonatally infected with mammary tumor virus (MTV) and MTV-free BALB/c females possess spleen cells capable of significant activity against target-MTV-induced mammary tumor cells in in vitro microcytotoxicity tests. The responses of the BALB/cfC3H and BALB/c females are different, however, on the basis of time studies. Further, the reactivity characteristic of virgin BALB/cfC3H females is increased in parous females, and part of this reactivity is subsequently lost in multiparous females bearing large tumors. BALB/cfC3H females possess reactive spleen cells as early as 3 weeks of age, indicating that response to MTV antigens develops soon after birth in these neonatally infected mice.", "contents": "In vitro detection of immune responses to MTV-induced mammary tumors: qualitative differences in response detected by time studies. Both BALB/cfC3H females neonatally infected with mammary tumor virus (MTV) and MTV-free BALB/c females possess spleen cells capable of significant activity against target-MTV-induced mammary tumor cells in in vitro microcytotoxicity tests. The responses of the BALB/cfC3H and BALB/c females are different, however, on the basis of time studies. Further, the reactivity characteristic of virgin BALB/cfC3H females is increased in parous females, and part of this reactivity is subsequently lost in multiparous females bearing large tumors. BALB/cfC3H females possess reactive spleen cells as early as 3 weeks of age, indicating that response to MTV antigens develops soon after birth in these neonatally infected mice."} {"id": "PMID:163277", "title": "Immunopathology of mouse hepatitis virus type 3 infection. Role of humoral and cell-mediated immunity in resistance mechanisms.", "content": "Humoral and cell-mediated immune responses were studied in resistant and susceptible strains of mice infected with mouse hepatitis virus type III (MHV 3). Virus was maintained by regular passages in susceptible DBA/2 mice and assayed in DBA/2 mice by LD-50 determination. Normal resistant A strain mice were able to clear the virus from liver, brain, and serum within 7 days after infection. No neutralizing antibody was found. Transfer of serum from immunized A strain mice was not effective in protecting susceptible DBA/2 mice against challenge with virus. In A strain animals resistance to MHV-3 developed rapidly during the 3rd week of life. During the period of susceptibility, newborns were protected neither by transplacental passages of anti-MHV-3 antibodies nor by injection of \"educated\" thymus cells.", "contents": "Immunopathology of mouse hepatitis virus type 3 infection. Role of humoral and cell-mediated immunity in resistance mechanisms. Humoral and cell-mediated immune responses were studied in resistant and susceptible strains of mice infected with mouse hepatitis virus type III (MHV 3). Virus was maintained by regular passages in susceptible DBA/2 mice and assayed in DBA/2 mice by LD-50 determination. Normal resistant A strain mice were able to clear the virus from liver, brain, and serum within 7 days after infection. No neutralizing antibody was found. Transfer of serum from immunized A strain mice was not effective in protecting susceptible DBA/2 mice against challenge with virus. In A strain animals resistance to MHV-3 developed rapidly during the 3rd week of life. During the period of susceptibility, newborns were protected neither by transplacental passages of anti-MHV-3 antibodies nor by injection of \"educated\" thymus cells."} {"id": "PMID:163278", "title": "In vitro studies on the cellular immune response of tumor-bearing mice to SV40-transformed cells.", "content": "Specific cell-mediated immunity to SV 40 tumor-specific transplantation antigen (TSTA) in mice undergoing tumorigenesis by syngeneic SV 40-transformed BALB/C cells was investigated by the macrophage migration inhibition (MMI) and transplantation rejection tests. Specific cellular reactivity to SV40 TSTA could be demonstrated in BALB/c mice early after tumor cell inoculation. This activity was no longer detectable during the later stages of tumor growth but was again demonstrable 2 weeks after tumor excision. Addition of an equal number of non-reactive peritoneal exudate (PE) cells from tumor-bearing mice to PE cells from mice immune to SV40 TSTA specifically abrogated the reactivity of the latter cells to soluble SV40 TSTA. When lymphoid cells with blocking activity were cultured in vitro they not only lost their blocking capacity but also regained their reactivity to SV40 TSTA in the MMI test. These findings indicate that tumor-bearing hosts possess lymphocytes specifically sensitized to the TSTA of the tumor and that the specific reactivity of these cells can be regained after culture in vitro.", "contents": "In vitro studies on the cellular immune response of tumor-bearing mice to SV40-transformed cells. Specific cell-mediated immunity to SV 40 tumor-specific transplantation antigen (TSTA) in mice undergoing tumorigenesis by syngeneic SV 40-transformed BALB/C cells was investigated by the macrophage migration inhibition (MMI) and transplantation rejection tests. Specific cellular reactivity to SV40 TSTA could be demonstrated in BALB/c mice early after tumor cell inoculation. This activity was no longer detectable during the later stages of tumor growth but was again demonstrable 2 weeks after tumor excision. Addition of an equal number of non-reactive peritoneal exudate (PE) cells from tumor-bearing mice to PE cells from mice immune to SV40 TSTA specifically abrogated the reactivity of the latter cells to soluble SV40 TSTA. When lymphoid cells with blocking activity were cultured in vitro they not only lost their blocking capacity but also regained their reactivity to SV40 TSTA in the MMI test. These findings indicate that tumor-bearing hosts possess lymphocytes specifically sensitized to the TSTA of the tumor and that the specific reactivity of these cells can be regained after culture in vitro."} {"id": "PMID:163279", "title": "Modulation of in vivo antibody responses by cholera toxin.", "content": "Treatment of mice with an exotoxin (0.01 mug to 1.0 mug) purified from Vibrio cholerae culture filtrates markedly influenced the immune response to sheep erythrocytes (SRBC) and the Escherichia coli lipopolysaccharide (LPS). Simultaneous administration of the toxin (CT) with antigen resulted in a delayed appearance of antibody plaque-forming cells (PFC) during the first few days after immunization, followed by a marked enhancement of both IgM and IgG PFC. The secondary immune response to SRBC was also similarly affected when CT was given together with a second inoculation of SRBC; i.e., a delay in appearance of hemolytic PFC followed by a markedly enhanced IgM and IgG PFC response. Treatment of mice with cholera toxin 1 to 3 days before SRBC or LPS was immunosuppressive. The effect of CT on the level of splenic cyclic AMP appeared related to the effects on antibody formation.", "contents": "Modulation of in vivo antibody responses by cholera toxin. Treatment of mice with an exotoxin (0.01 mug to 1.0 mug) purified from Vibrio cholerae culture filtrates markedly influenced the immune response to sheep erythrocytes (SRBC) and the Escherichia coli lipopolysaccharide (LPS). Simultaneous administration of the toxin (CT) with antigen resulted in a delayed appearance of antibody plaque-forming cells (PFC) during the first few days after immunization, followed by a marked enhancement of both IgM and IgG PFC. The secondary immune response to SRBC was also similarly affected when CT was given together with a second inoculation of SRBC; i.e., a delay in appearance of hemolytic PFC followed by a markedly enhanced IgM and IgG PFC response. Treatment of mice with cholera toxin 1 to 3 days before SRBC or LPS was immunosuppressive. The effect of CT on the level of splenic cyclic AMP appeared related to the effects on antibody formation."} {"id": "PMID:163280", "title": "The modulation of spontaneous and anti-Ig-stimulated motility of lymphocytes by cyclic nucleotides and adrenergic and cholinergic agents.", "content": "Translational movement in B lymphocytes was stimulated by anti-Ig antibody. Drugs that are presumed to elevate cyclic AMP stopped this stimulated motility. Such was the case with dibutyryl cAMP and theophylline, cholera enterotoxin, and isoproterenol, a beta adrenergic agonist. Conversely, in the absence of anti-immunoglobulin antibody, cyclic GMP and the cholinergic drugs acetylcholine and carbamylcholine increased spontaneous motility of lymphocytes, with the B class of lymphocytes demonstrating greater responsiveness. The increase in motility brought about by cholinergic drugs was totally stopped by atropine, suggesting that the B lymphocyte surface contains a cholinergic receptor. The inhibition of anti-immunoglobulin-stimulated movement produced by cyclic AMP was not observed if the cells were first incubated with colchicine, the microtubular-disrupting drug. This suggests that the cyclic AMP-decreased motility was brought about by the increased stabilization of microtubules. Lymphocyte motility was dissociable from other early events subsequent to binding of anti-immunoglobulin antibodies: patching, capping, and endocytosis of complexes were unaffected by cyclic AMP, cyclic GMP, or drugs of the adrenergic or cholinergic systems.", "contents": "The modulation of spontaneous and anti-Ig-stimulated motility of lymphocytes by cyclic nucleotides and adrenergic and cholinergic agents. Translational movement in B lymphocytes was stimulated by anti-Ig antibody. Drugs that are presumed to elevate cyclic AMP stopped this stimulated motility. Such was the case with dibutyryl cAMP and theophylline, cholera enterotoxin, and isoproterenol, a beta adrenergic agonist. Conversely, in the absence of anti-immunoglobulin antibody, cyclic GMP and the cholinergic drugs acetylcholine and carbamylcholine increased spontaneous motility of lymphocytes, with the B class of lymphocytes demonstrating greater responsiveness. The increase in motility brought about by cholinergic drugs was totally stopped by atropine, suggesting that the B lymphocyte surface contains a cholinergic receptor. The inhibition of anti-immunoglobulin-stimulated movement produced by cyclic AMP was not observed if the cells were first incubated with colchicine, the microtubular-disrupting drug. This suggests that the cyclic AMP-decreased motility was brought about by the increased stabilization of microtubules. Lymphocyte motility was dissociable from other early events subsequent to binding of anti-immunoglobulin antibodies: patching, capping, and endocytosis of complexes were unaffected by cyclic AMP, cyclic GMP, or drugs of the adrenergic or cholinergic systems."} {"id": "PMID:163281", "title": "Induction of lymphocyte cytotoxicity by modification of the effector or target cells with periodate or with neuraminidase and galactose oxidase.", "content": "Treatment of mouse spleen cells with periodate (NaIO4) or with neuraminidase and galactose oxidase (NAGO) induces blastogenesis and renders the cells cytotoxic to mastocytoma (P815) target cells. Treatment of target cells (P815 cells and turkey erythrocytes) with NaIO4 or with NAGO renders them susceptible to cytolysis by untreated mouse spleen cells. The cytotoxicity induced by NaIO4 is reduced upon reacting the NaIO4-treated, effector or target cells with borohydride or hydroxylamine. Thus the formation of free surface aldehydes on either the effector or target cell induced a cytotoxic effect. It is postulated that cross-linkage via a Schiff base between effector and target cell initiates the cytotoxic effect. Cytotoxicity induced by NaIO4 or NAGO is immunologically nonspecific and is independent of major antigenic differences between effector and target cells. Phagocytic cells are not involved in NaIO4-or NAGO-induced cytotoxicity toward P815 target cells.", "contents": "Induction of lymphocyte cytotoxicity by modification of the effector or target cells with periodate or with neuraminidase and galactose oxidase. Treatment of mouse spleen cells with periodate (NaIO4) or with neuraminidase and galactose oxidase (NAGO) induces blastogenesis and renders the cells cytotoxic to mastocytoma (P815) target cells. Treatment of target cells (P815 cells and turkey erythrocytes) with NaIO4 or with NAGO renders them susceptible to cytolysis by untreated mouse spleen cells. The cytotoxicity induced by NaIO4 is reduced upon reacting the NaIO4-treated, effector or target cells with borohydride or hydroxylamine. Thus the formation of free surface aldehydes on either the effector or target cell induced a cytotoxic effect. It is postulated that cross-linkage via a Schiff base between effector and target cell initiates the cytotoxic effect. Cytotoxicity induced by NaIO4 or NAGO is immunologically nonspecific and is independent of major antigenic differences between effector and target cells. Phagocytic cells are not involved in NaIO4-or NAGO-induced cytotoxicity toward P815 target cells."} {"id": "PMID:163282", "title": "The initiation of mast cell degranulation: activation at the cell membrane.", "content": "The low molecular weight mast cell activator, polymyxin B, has been covalently bound to an insoluble matrix of Sepharose 4B. It has been demonstrated that mast cells in preparations of rat peritoneal cells bind to Sepharose 4B-polymyxin B beads but not to control beads. The bound cells are stimulated to degranulate by this interaction at the cell membrane with the resultant release of biogenic amines.", "contents": "The initiation of mast cell degranulation: activation at the cell membrane. The low molecular weight mast cell activator, polymyxin B, has been covalently bound to an insoluble matrix of Sepharose 4B. It has been demonstrated that mast cells in preparations of rat peritoneal cells bind to Sepharose 4B-polymyxin B beads but not to control beads. The bound cells are stimulated to degranulate by this interaction at the cell membrane with the resultant release of biogenic amines."} {"id": "PMID:163283", "title": "Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes.", "content": "The production of superoxide radicals (O2-) by human granulocytes after phagocytosis of latex particles has been studied as a function of cell, latex, and cytochrome c concentration. Under the chosen conditions, latex phagocytosis stimulated the reduction of cytochrome c by O2- sevenfold to 420 mumoles per 10-10 granulocytes per hour. At high cytochrome c concentrations, this value increased to 800 to 1,000 mumoles per 10-10 granulocytes per hour. These amounts suggest that O2- plays an important role in the formation of H2O2 during the phagocytic process. We propose that the extra oxygen consumed in the respiratory burst is first reduced to O2-, possibly by ascorbate, before being converted to H2O2. No stimulation of the superoxide radical formation was found in the phagocytizing granulocytes of two patients with chronic granulomatous disease, and intermediate values were found for the heterozygotes of this deficiency.", "contents": "Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes. The production of superoxide radicals (O2-) by human granulocytes after phagocytosis of latex particles has been studied as a function of cell, latex, and cytochrome c concentration. Under the chosen conditions, latex phagocytosis stimulated the reduction of cytochrome c by O2- sevenfold to 420 mumoles per 10-10 granulocytes per hour. At high cytochrome c concentrations, this value increased to 800 to 1,000 mumoles per 10-10 granulocytes per hour. These amounts suggest that O2- plays an important role in the formation of H2O2 during the phagocytic process. We propose that the extra oxygen consumed in the respiratory burst is first reduced to O2-, possibly by ascorbate, before being converted to H2O2. No stimulation of the superoxide radical formation was found in the phagocytizing granulocytes of two patients with chronic granulomatous disease, and intermediate values were found for the heterozygotes of this deficiency."} {"id": "PMID:163284", "title": "The transport of triglyceride in the high-density lipoproteins of human plasma.", "content": "The metabolism of the small pool of triglyceride in human high-density lipoproteins (HDL) has been studied. In 28 postabsorptive and unmedicated subjects the previously reported reciprocal relationships between the concentration of very low-density lipoprotein (VLDL) lipids and HDL cholesterol was confirmed. It was also found that the HDL triglyceride correlated positively and significantly with the concentration of VLDL triglyceride, and there was a significant negative correlation between the concentrations of triglyceride and cholesterol in HDL. Five normal and 3 hypertriglyceridemic subjects were given 5,000 units of heparin intravenously. Not only was there a pronounced reduction in VLDL triglyceride, but there was a 60 to 80 per cent reduction in HDL triglyceride; the low-density lipoprotein (LDL) triglyceride was unchanged. To test a possible precursor-product relationship between the triglyceride pools in VLDL and HDL, 5 subjects were given an intravenous pulse injection of (14-C)-palmitic acid. The specific activity-time curves of triglyceride in VLDL and HDL did not conform to a typical precursor-product relationship; rather the HDL curve reached its peak well before it crossed the VLDL curve, quite compatible with an origin of HDL triglyceride which was independent of VLDL. However, when the lipoproteins of density smaller than 1.006 (VLDL and chylomicrons) were labeled in the intestine after an oral tracer dose of (3-H)-palmitic acid in 2 subjects, the relationship of the triglyceride labeling in HDL to that in d smaller than 1.006 lipoproteins was very similar to the relationship observed after the intravenous dose. Although an independent intestinal origin of HDL triglyceride could not be excluded, this result did suggest that the labeling of triglyceride in d smaller than 1.006 lipoproteins and in HDL was related and was consistent with a transfer from the larger lipoproteins to the HDL. In three subjects given a constant intravenous infusion of (3-H)-palmitic acid, the specific activity of triglyceride in VLDL became constant after 3 to 4 hours; it also became constant in the HDL after about 4 hours but at a level of only 40 to 70 per cent of the VLDL level. It appeared that 30 to 60 per cent of the HDL triglyceride was either derived from an unlabeled source or else turned over too slowly to become labeled to any extent during the infusions. Whatever the explanation, the same phenomenon would be likely to influence the level of the peak specific activity of HDL triglyceride after the pulse intravenous injections of label. It is possible that the specific activity of the \"labeled\" fraction of HDL triglyceride may have reached its peak at the point at which it crossed the VLDL curve, which would be consistent with a precursor-product relationship between VLDL and one fraction of the HDL triglyceride. It has been concluded that HDL triglyceride is heterogeneous and includes at least one pool, possibly transferred from VLDL, which is relatively rapidly turning over.", "contents": "The transport of triglyceride in the high-density lipoproteins of human plasma. The metabolism of the small pool of triglyceride in human high-density lipoproteins (HDL) has been studied. In 28 postabsorptive and unmedicated subjects the previously reported reciprocal relationships between the concentration of very low-density lipoprotein (VLDL) lipids and HDL cholesterol was confirmed. It was also found that the HDL triglyceride correlated positively and significantly with the concentration of VLDL triglyceride, and there was a significant negative correlation between the concentrations of triglyceride and cholesterol in HDL. Five normal and 3 hypertriglyceridemic subjects were given 5,000 units of heparin intravenously. Not only was there a pronounced reduction in VLDL triglyceride, but there was a 60 to 80 per cent reduction in HDL triglyceride; the low-density lipoprotein (LDL) triglyceride was unchanged. To test a possible precursor-product relationship between the triglyceride pools in VLDL and HDL, 5 subjects were given an intravenous pulse injection of (14-C)-palmitic acid. The specific activity-time curves of triglyceride in VLDL and HDL did not conform to a typical precursor-product relationship; rather the HDL curve reached its peak well before it crossed the VLDL curve, quite compatible with an origin of HDL triglyceride which was independent of VLDL. However, when the lipoproteins of density smaller than 1.006 (VLDL and chylomicrons) were labeled in the intestine after an oral tracer dose of (3-H)-palmitic acid in 2 subjects, the relationship of the triglyceride labeling in HDL to that in d smaller than 1.006 lipoproteins was very similar to the relationship observed after the intravenous dose. Although an independent intestinal origin of HDL triglyceride could not be excluded, this result did suggest that the labeling of triglyceride in d smaller than 1.006 lipoproteins and in HDL was related and was consistent with a transfer from the larger lipoproteins to the HDL. In three subjects given a constant intravenous infusion of (3-H)-palmitic acid, the specific activity of triglyceride in VLDL became constant after 3 to 4 hours; it also became constant in the HDL after about 4 hours but at a level of only 40 to 70 per cent of the VLDL level. It appeared that 30 to 60 per cent of the HDL triglyceride was either derived from an unlabeled source or else turned over too slowly to become labeled to any extent during the infusions. Whatever the explanation, the same phenomenon would be likely to influence the level of the peak specific activity of HDL triglyceride after the pulse intravenous injections of label. It is possible that the specific activity of the \"labeled\" fraction of HDL triglyceride may have reached its peak at the point at which it crossed the VLDL curve, which would be consistent with a precursor-product relationship between VLDL and one fraction of the HDL triglyceride. It has been concluded that HDL triglyceride is heterogeneous and includes at least one pool, possibly transferred from VLDL, which is relatively rapidly turning over."} {"id": "PMID:163285", "title": "A radioisotopic assay for proline oxidase activity.", "content": "We developed a radioisotopic assay for proline oxidase in which product deltal-pyrroline-5-carboxylate-14-C is reacted with o-aminobenzaldehyde and the radioactivity trapped as the dihydroquinazolinium compound is recovered by ion-exchange chromatography. The sensitivity of this method allows the measurement of proline oxidase activity in small specimens (10 to 20 mg.) of liver.", "contents": "A radioisotopic assay for proline oxidase activity. We developed a radioisotopic assay for proline oxidase in which product deltal-pyrroline-5-carboxylate-14-C is reacted with o-aminobenzaldehyde and the radioactivity trapped as the dihydroquinazolinium compound is recovered by ion-exchange chromatography. The sensitivity of this method allows the measurement of proline oxidase activity in small specimens (10 to 20 mg.) of liver."} {"id": "PMID:163286", "title": "A case of oropharyngeal chordoma.", "content": "A case of cervical chordoma without vertebral involvement is presented. The diffculty in histological diagnosis is described. Treatment by radiotherapy and surgery is described and discussed.", "contents": "A case of oropharyngeal chordoma. A case of cervical chordoma without vertebral involvement is presented. The diffculty in histological diagnosis is described. Treatment by radiotherapy and surgery is described and discussed."} {"id": "PMID:163287", "title": "Deoxypyrimidine kinases of herpes simplex viruses types 1 and 2: comparison of serological and structural properties.", "content": "The kinetics of formation, the stability at 40 degrees C and the serological properties of thymidine kinase and deoxycytidine kinase activities induced by herpes simplex virus have been examined. The results are consistent with the hypothesis that both activities are carried on the same molecule-a deoxypyrimidine kinase. Mutants deficient in deoxypyrimidine kinase have been used to produce, by absorption of general antisera, deoxypyrimidine kinase-specific antisera. Using immunoprecipitation and SDS-polyacrylamide gel electrophoresis, only one size of polypeptide (mol. wt. 42400 plus or minus 200) has been found, constituting the type 2 enzyme. This is close to published values for the type i enzyme but co-electrophoresis demonstrated that the polypeptide of the type i enzyme was slightly bigger.", "contents": "Deoxypyrimidine kinases of herpes simplex viruses types 1 and 2: comparison of serological and structural properties. The kinetics of formation, the stability at 40 degrees C and the serological properties of thymidine kinase and deoxycytidine kinase activities induced by herpes simplex virus have been examined. The results are consistent with the hypothesis that both activities are carried on the same molecule-a deoxypyrimidine kinase. Mutants deficient in deoxypyrimidine kinase have been used to produce, by absorption of general antisera, deoxypyrimidine kinase-specific antisera. Using immunoprecipitation and SDS-polyacrylamide gel electrophoresis, only one size of polypeptide (mol. wt. 42400 plus or minus 200) has been found, constituting the type 2 enzyme. This is close to published values for the type i enzyme but co-electrophoresis demonstrated that the polypeptide of the type i enzyme was slightly bigger."} {"id": "PMID:163288", "title": "Electron microscopic studies on assembly of herpes simplex virus upon removal of hydroxyurea block.", "content": "The release of hydroxyurea-treated, herpes simplex virus-infected cells from the drug-induced block resulted in the prompt assembly of infectious virus. Electron microscope observations at sequential intervals following removal of the drug revealed considerable synchrony of replication. This synchrony permitted stages in the complex process of core assembly to be examined in detail. The data suggest that after partial or complete assembly the nucleoprotein enters the differentiated capsid to become enfolded.", "contents": "Electron microscopic studies on assembly of herpes simplex virus upon removal of hydroxyurea block. The release of hydroxyurea-treated, herpes simplex virus-infected cells from the drug-induced block resulted in the prompt assembly of infectious virus. Electron microscope observations at sequential intervals following removal of the drug revealed considerable synchrony of replication. This synchrony permitted stages in the complex process of core assembly to be examined in detail. The data suggest that after partial or complete assembly the nucleoprotein enters the differentiated capsid to become enfolded."} {"id": "PMID:163289", "title": "Virus development in enucleate cells: echovirus, poliovirus, pseudorabies virus, reovirus, respiratory syncytial virus and Semliki Forest virus.", "content": "A group of RNA viruses, echovirus, poliovirus, reovirus, respiratory syncytial virus and Semliki Forest virus have been examined for ability to grow in enucleate African green monkey kidney (BSCi) cells. Semliki Forest virus produced an almost normal yield of virus but poliovirus, echovirus, reovirus and respiratory syncytial virus, although showing clear evidence of virus replication when compared with a nuclear DNA virus (pseudorabies virus) gave much lower yields than those from nucleate cells. Analysis of enucleate cells infected with echovirus and reovirus showed no evidence of a specific block in the synthesis of any virus-specified polypeptide. Infection with vesicular stomatitis virus at intervals after enucleation demonstrated a diminishing ability to support virus growth with increasing time. It is suggested that the yield of virus obtained from an enucleate cell is related to the length of the growth cycle of the virus, the reduced yield obtained with some viruses reflecting the declining ability of the enucleate cell to support virus growth.", "contents": "Virus development in enucleate cells: echovirus, poliovirus, pseudorabies virus, reovirus, respiratory syncytial virus and Semliki Forest virus. A group of RNA viruses, echovirus, poliovirus, reovirus, respiratory syncytial virus and Semliki Forest virus have been examined for ability to grow in enucleate African green monkey kidney (BSCi) cells. Semliki Forest virus produced an almost normal yield of virus but poliovirus, echovirus, reovirus and respiratory syncytial virus, although showing clear evidence of virus replication when compared with a nuclear DNA virus (pseudorabies virus) gave much lower yields than those from nucleate cells. Analysis of enucleate cells infected with echovirus and reovirus showed no evidence of a specific block in the synthesis of any virus-specified polypeptide. Infection with vesicular stomatitis virus at intervals after enucleation demonstrated a diminishing ability to support virus growth with increasing time. It is suggested that the yield of virus obtained from an enucleate cell is related to the length of the growth cycle of the virus, the reduced yield obtained with some viruses reflecting the declining ability of the enucleate cell to support virus growth."} {"id": "PMID:163290", "title": "Effect of interferon on induction of S antigen by polyoma virus in BHK 21 cells.", "content": "A new surface antigen (S antigen) can be detected by immunofluorescence during the abortive transformation of hamster cells by polyoma virus. It was found that addition of interferon greatly reduces the percentage of cells positive for S antigen.", "contents": "Effect of interferon on induction of S antigen by polyoma virus in BHK 21 cells. A new surface antigen (S antigen) can be detected by immunofluorescence during the abortive transformation of hamster cells by polyoma virus. It was found that addition of interferon greatly reduces the percentage of cells positive for S antigen."} {"id": "PMID:163298", "title": "Nerve supply and experimental myotonia in rats.", "content": "20, 25-Diazacholesterol does not induce myotonia in denervated mammalian skeletal muscle, and cordotomy also renders the muscles resistant to the induction of myotonia. Denervation of muscle already rendered myotonic, has no effect on the intensity of the phenomenon. Finally, tenotomy and posterior rhizotomy leave the myotonic activity in the \"deafferentated\" muscles unchanged. These findings are discussed in relation to \"trophic\" influences of the motor pathways on the postsynaptic structures of skeletal muscle.", "contents": "Nerve supply and experimental myotonia in rats. 20, 25-Diazacholesterol does not induce myotonia in denervated mammalian skeletal muscle, and cordotomy also renders the muscles resistant to the induction of myotonia. Denervation of muscle already rendered myotonic, has no effect on the intensity of the phenomenon. Finally, tenotomy and posterior rhizotomy leave the myotonic activity in the \"deafferentated\" muscles unchanged. These findings are discussed in relation to \"trophic\" influences of the motor pathways on the postsynaptic structures of skeletal muscle."} {"id": "PMID:163299", "title": "Stages in fibre breakdown in Duchenne muscular dystrophy. An electron-microscopic study.", "content": "A scheme is presented which divides the process of fibre breakdown in Duchenne muscular dystrophy into 5 sequential stages. In Stage 1 the fibre appears superficially normal although there are subtle changes in the relative volumes of the fibre components. In Stage 2 localised overcontraction of the myofibrils results in excessive stretching of the sarcomeres in other regions of the fibre. This continuing process results in the formation of contraction clumps in which the contractile filaments form an increasingly homogeneous mass. By the final stage the normal structural features of the fibre have completely disappeared and it is invaded by macrophages. It is suggested that the central process of myofibril clumping results from a localised inability of the sarcomeres to relax which implies a defect in the mitochondria, Z-line or sarcoplasmic reticulum. This is discussed in relation to other workers' findings of a decrease in the calcium-accumulating capacity of the sarcoplasmic reticulum in Duchenne muscular dystrophy.", "contents": "Stages in fibre breakdown in Duchenne muscular dystrophy. An electron-microscopic study. A scheme is presented which divides the process of fibre breakdown in Duchenne muscular dystrophy into 5 sequential stages. In Stage 1 the fibre appears superficially normal although there are subtle changes in the relative volumes of the fibre components. In Stage 2 localised overcontraction of the myofibrils results in excessive stretching of the sarcomeres in other regions of the fibre. This continuing process results in the formation of contraction clumps in which the contractile filaments form an increasingly homogeneous mass. By the final stage the normal structural features of the fibre have completely disappeared and it is invaded by macrophages. It is suggested that the central process of myofibril clumping results from a localised inability of the sarcomeres to relax which implies a defect in the mitochondria, Z-line or sarcoplasmic reticulum. This is discussed in relation to other workers' findings of a decrease in the calcium-accumulating capacity of the sarcoplasmic reticulum in Duchenne muscular dystrophy."} {"id": "PMID:163300", "title": "Rebound phenomenon complicating cerebral dehydration with glycerol. Case report.", "content": "A patient with glioblastoma multiforme of the brain was treated with both intravenous and oral glycerol as well as intravenous mannitol in an attempt to reduce increased intracranial pressure. After an initial lowering of the cerebrospinal fluid (CSF) pressure to near normal values during continuous glycerol administration, a secondary rise in CSF pressure above the initial level occurred despite a persistent elevation of plasma osmolality (315 mOsm/kg) and glycerol level (30 mmole/l). Similarly, 4 hours after the administration of a single oral dose of glycerol, CSF pressure increased to levels higher (700 mm H2O) than the original baseline (400 mm H2O).", "contents": "Rebound phenomenon complicating cerebral dehydration with glycerol. Case report. A patient with glioblastoma multiforme of the brain was treated with both intravenous and oral glycerol as well as intravenous mannitol in an attempt to reduce increased intracranial pressure. After an initial lowering of the cerebrospinal fluid (CSF) pressure to near normal values during continuous glycerol administration, a secondary rise in CSF pressure above the initial level occurred despite a persistent elevation of plasma osmolality (315 mOsm/kg) and glycerol level (30 mmole/l). Similarly, 4 hours after the administration of a single oral dose of glycerol, CSF pressure increased to levels higher (700 mm H2O) than the original baseline (400 mm H2O)."} {"id": "PMID:163301", "title": "Uptake of 99mTc bone-scanning agent by lungs with metastatic calcification.", "content": "Uptake of 99mTc bone-scanning agent into lungs containing metastatic calcification was demonstrated in a patient with a carcinosarcoma of the bladder. This gives further support to the hypothesis that 99mTc bone agents are associated with hydroxyapatite.", "contents": "Uptake of 99mTc bone-scanning agent by lungs with metastatic calcification. Uptake of 99mTc bone-scanning agent into lungs containing metastatic calcification was demonstrated in a patient with a carcinosarcoma of the bladder. This gives further support to the hypothesis that 99mTc bone agents are associated with hydroxyapatite."} {"id": "PMID:163302", "title": "Effects of semistarvation on rat liver, kidney, and heart mitochondrial function.", "content": "Two groups of rats were provided simultaneously with a commercial stock diet for a period of 7 days. One group was fed ad libitum (control), and the other was restricted to one-fourth of the daily intake of control animals (semistarved). Body weight declined significantly in semistarved rats whereas body weight of controls increased over the 7-day period. The following were determined in vitro on mitochondria isolated from liver, kidney, and heart tissues of both groups: substrate-stimulated and DNP-uncoupled respiratory rates; specific acivities of the Krebs cycle dehydrogenases, and cytochrome c oxidase. Degradative effects of reduced food intake on mitochondrial function were observed. Uncoupled respiratory rates of liver and kidney mitochondria (using succinate as substrate) and heart mitochondria (using alpha-ketoglutarate and pyruvate) were lower. Also lower were activities of isocitrate dehydrogenase, NADP: isocitrate dehydrogenases, transhydrogenase, succinate dehydrogenase, and cytochrome c oxidase of heart mitochondria, transhdrogenase of liver mitochondria, and isocitrate dehydrogenase and transhydrogenase of kidney mitochondria. Such decreases in enzyme activities under conditions of dietary protein deficiency might have their basis in breakdown rates exceeding synthesis rates or result from partial inactivation of existing enzyme protein. Thus, there is evidence that responses to semistarvation of such parameters of mitochondrial function may differ among various tissues. In addition, liver and kidney citrate levels were lower and heart citrate level higher with semistarvation.", "contents": "Effects of semistarvation on rat liver, kidney, and heart mitochondrial function. Two groups of rats were provided simultaneously with a commercial stock diet for a period of 7 days. One group was fed ad libitum (control), and the other was restricted to one-fourth of the daily intake of control animals (semistarved). Body weight declined significantly in semistarved rats whereas body weight of controls increased over the 7-day period. The following were determined in vitro on mitochondria isolated from liver, kidney, and heart tissues of both groups: substrate-stimulated and DNP-uncoupled respiratory rates; specific acivities of the Krebs cycle dehydrogenases, and cytochrome c oxidase. Degradative effects of reduced food intake on mitochondrial function were observed. Uncoupled respiratory rates of liver and kidney mitochondria (using succinate as substrate) and heart mitochondria (using alpha-ketoglutarate and pyruvate) were lower. Also lower were activities of isocitrate dehydrogenase, NADP: isocitrate dehydrogenases, transhydrogenase, succinate dehydrogenase, and cytochrome c oxidase of heart mitochondria, transhdrogenase of liver mitochondria, and isocitrate dehydrogenase and transhydrogenase of kidney mitochondria. Such decreases in enzyme activities under conditions of dietary protein deficiency might have their basis in breakdown rates exceeding synthesis rates or result from partial inactivation of existing enzyme protein. Thus, there is evidence that responses to semistarvation of such parameters of mitochondrial function may differ among various tissues. In addition, liver and kidney citrate levels were lower and heart citrate level higher with semistarvation."} {"id": "PMID:163304", "title": "Case 11, Part 2. Angiokeratoma corporis diffusum (Fabry's disease).", "content": "A case of Fabry's disease is reported. The patient had multiple supernumerary, impacted, and unerupted teeth and other developmental abnormalities of the facial skeleton. The patient tolerated surgical removal of impacted and unerupted teeth without complications. However, this did not relieve the facial pain. The expected prognosis of this patient will be a continued vascular and renal degeneration with death probable before the age of 50 years if the disease is untreated. Currently, the patient is being considered as a possible candidate for renal transplantation.", "contents": "Case 11, Part 2. Angiokeratoma corporis diffusum (Fabry's disease). A case of Fabry's disease is reported. The patient had multiple supernumerary, impacted, and unerupted teeth and other developmental abnormalities of the facial skeleton. The patient tolerated surgical removal of impacted and unerupted teeth without complications. However, this did not relieve the facial pain. The expected prognosis of this patient will be a continued vascular and renal degeneration with death probable before the age of 50 years if the disease is untreated. Currently, the patient is being considered as a possible candidate for renal transplantation."} {"id": "PMID:163305", "title": "The role of adenoviruses in the pertussis syndrome.", "content": "To define the role of adenoviruses in the pertussis syndrome, a study was done of a group of 134 children with clinical pertussis and a healthy control population of similar age, race, sex, and socioeconomic status. Adenovirus infections occurred in 30 (22.4%) of 134 patients with the pertussis syndrome and 5 (4.9%) of 101 control subjects (p smaller than 0.001). B. pertussis was recovered from 46 (34.3%) patients, and from 18 (39.1%) of these patients adenoviruses were also isolated. Although adenovirus infections also occurred in patients with the pertussis syndrome with negative cultures for B. pertussis, the rate, 12 of 88 patients (13.6%), was significantly lower (p smaller than 0.001). The clinical course was similar irrespective of the results of bacterial or viral cultures. These data substantiate the frequent association of adenoviruses with the pertussis syndrome, It would appear that adenoviruses do not usually have an independent role in the pathogenesis of the pertussis syndrome since we found them so commonly to be one agent in a mixed infection.", "contents": "The role of adenoviruses in the pertussis syndrome. To define the role of adenoviruses in the pertussis syndrome, a study was done of a group of 134 children with clinical pertussis and a healthy control population of similar age, race, sex, and socioeconomic status. Adenovirus infections occurred in 30 (22.4%) of 134 patients with the pertussis syndrome and 5 (4.9%) of 101 control subjects (p smaller than 0.001). B. pertussis was recovered from 46 (34.3%) patients, and from 18 (39.1%) of these patients adenoviruses were also isolated. Although adenovirus infections also occurred in patients with the pertussis syndrome with negative cultures for B. pertussis, the rate, 12 of 88 patients (13.6%), was significantly lower (p smaller than 0.001). The clinical course was similar irrespective of the results of bacterial or viral cultures. These data substantiate the frequent association of adenoviruses with the pertussis syndrome, It would appear that adenoviruses do not usually have an independent role in the pathogenesis of the pertussis syndrome since we found them so commonly to be one agent in a mixed infection."} {"id": "PMID:163307", "title": "Plasma lipid values and lipoprotein patterns during adolescence in boys.", "content": "Lipid studies were performed on fasting plasma samples in 214 healthy adolescent boys, 11-19 years of age. Ranges of normal values for plasma cholesterol and triglyceride concentrations, and normal lipoprotein patterns were established for this age group. The boys were grouped according to puberty rating. A significant increase in triglyceride values was obtained with adolescent maturity. Plasma cholesterol values did not change with age or puberty rating. One boy had hypercholesterolemia and a lipoprotein pattern consistent with Type II hyperlipoproteinemia (Fredrickson). Seventeen boys, all of whom had reached adolescent maturity, had elevated triglyceride values and a marked increase in pre-beta-lipoprotein. It appears from this study that increased concentrations of triglyceride and Type IV hyperlipoproteinemia of Fredrickson may be detected as boys reach maturity at adolescence.", "contents": "Plasma lipid values and lipoprotein patterns during adolescence in boys. Lipid studies were performed on fasting plasma samples in 214 healthy adolescent boys, 11-19 years of age. Ranges of normal values for plasma cholesterol and triglyceride concentrations, and normal lipoprotein patterns were established for this age group. The boys were grouped according to puberty rating. A significant increase in triglyceride values was obtained with adolescent maturity. Plasma cholesterol values did not change with age or puberty rating. One boy had hypercholesterolemia and a lipoprotein pattern consistent with Type II hyperlipoproteinemia (Fredrickson). Seventeen boys, all of whom had reached adolescent maturity, had elevated triglyceride values and a marked increase in pre-beta-lipoprotein. It appears from this study that increased concentrations of triglyceride and Type IV hyperlipoproteinemia of Fredrickson may be detected as boys reach maturity at adolescence."} {"id": "PMID:163308", "title": "A laboratory procedure for copperplating rubber base impressions.", "content": "A method for producing electroformed copper dies from rubber base impressions has been described. Castings made by the use of such dies have met the standards set by several critical dentists.", "contents": "A laboratory procedure for copperplating rubber base impressions. A method for producing electroformed copper dies from rubber base impressions has been described. Castings made by the use of such dies have met the standards set by several critical dentists."} {"id": "PMID:163309", "title": "Luteoma of pregnancy: report of a case and review of the literature.", "content": "A case of a unilateral, non-virilizing pregnancy luteoma in a 28 year old Caucasian female resulted in good health more than six years after removal of the lesion. Theories on the histogenesis of the lesion are briefly recounted and the literature is reviewed. This case appears to be number 62 in the world literature.", "contents": "Luteoma of pregnancy: report of a case and review of the literature. A case of a unilateral, non-virilizing pregnancy luteoma in a 28 year old Caucasian female resulted in good health more than six years after removal of the lesion. Theories on the histogenesis of the lesion are briefly recounted and the literature is reviewed. This case appears to be number 62 in the world literature."} {"id": "PMID:163310", "title": "Modification of nuclear restriction in vitro by plasma from tumor-bearing animals.", "content": "Putative regulatory macromolecules, which may be useful in diagnosis or tumor detection, were identified in the peripheral blood plasma of tumor-bearing animals. We monitored the components by measuring their ability to stimulate messenger RNA (mRNA) release from isolated nuclei in a cell-free system of rat liver nuclei in fortified homologous cytosol. This in vitro test system exhibited near-normal in vivo nuclear RNA restriction. When added to the assay at a protein concentration of 3.0 mg/ml, dialyzed plasma from rats or mice with chemically induced transplantable or primary tumors stimulated mRNA release from 87% to more than 300% over control plasma from normal rats. Plasma from partially hepatectomized rats stimulated only 26% over control plasma. The test system derived from rat liver seemed to permit the monitoring of plasma from other species. Available evidence, particularly relating to tumor-host-interaction, suggests, but does not prove, that regulatory components are released from the tumor cells to the circulation.", "contents": "Modification of nuclear restriction in vitro by plasma from tumor-bearing animals. Putative regulatory macromolecules, which may be useful in diagnosis or tumor detection, were identified in the peripheral blood plasma of tumor-bearing animals. We monitored the components by measuring their ability to stimulate messenger RNA (mRNA) release from isolated nuclei in a cell-free system of rat liver nuclei in fortified homologous cytosol. This in vitro test system exhibited near-normal in vivo nuclear RNA restriction. When added to the assay at a protein concentration of 3.0 mg/ml, dialyzed plasma from rats or mice with chemically induced transplantable or primary tumors stimulated mRNA release from 87% to more than 300% over control plasma from normal rats. Plasma from partially hepatectomized rats stimulated only 26% over control plasma. The test system derived from rat liver seemed to permit the monitoring of plasma from other species. Available evidence, particularly relating to tumor-host-interaction, suggests, but does not prove, that regulatory components are released from the tumor cells to the circulation."} {"id": "PMID:163311", "title": "Effect of beta-oxidized nitrosamines on syrian hamsters. III. 2,2'-Dihydroxydi-n-propylnitrosamine.", "content": "2, 2-Dihydroxy-di-n-propylnitrosamine (DHPN), an assumed metabolite of di-n-propylnitrosamine (DPN), injected subcutaneously once weekly for life, was carcinogenic in Syrian hamsters. The main target organs were the respiratory tract, pancreas, liver, and kidneys. In the respiratory system the most affected segments were the nasal cavities and the lungs. Adenomas and adenocarcinomas, mostly of ductal origin, were induced in the pancreas. Liver neoplasms were hemangloendotheliomas, angiosarcomas, hepatocellular adenomas, cholangiomas, and cholangiocarcinomas. Kidney neoplasms were adenomas and adenocarcinomas. The morphology of the induced neoplasms was described, as well as the effects of DHPN, compared to those another possible metabolite of DPN, 2-hydroxypropyl-n-propylnitrosamine (2-HPPN), which is formed in vivo with only 1 aliphatic chain degraded via theta-oxidation.", "contents": "Effect of beta-oxidized nitrosamines on syrian hamsters. III. 2,2'-Dihydroxydi-n-propylnitrosamine. 2, 2-Dihydroxy-di-n-propylnitrosamine (DHPN), an assumed metabolite of di-n-propylnitrosamine (DPN), injected subcutaneously once weekly for life, was carcinogenic in Syrian hamsters. The main target organs were the respiratory tract, pancreas, liver, and kidneys. In the respiratory system the most affected segments were the nasal cavities and the lungs. Adenomas and adenocarcinomas, mostly of ductal origin, were induced in the pancreas. Liver neoplasms were hemangloendotheliomas, angiosarcomas, hepatocellular adenomas, cholangiomas, and cholangiocarcinomas. Kidney neoplasms were adenomas and adenocarcinomas. The morphology of the induced neoplasms was described, as well as the effects of DHPN, compared to those another possible metabolite of DPN, 2-hydroxypropyl-n-propylnitrosamine (2-HPPN), which is formed in vivo with only 1 aliphatic chain degraded via theta-oxidation."} {"id": "PMID:163312", "title": "Immunization of Rous sarcoma virus-inoculated marmosets with BCG and transformed allogeneic cells.", "content": "The effects of specific immunotherapy with allogeneic cells transformed by Schmidt-Ruppin Rous sarcoma virus (SR-RSV), of treatment with BCG, and of surgery on the growth of SR-RSV-induced sarcomas in white-lipped marmosets were studied. Tumor incidence, tumor progression, and survival did not differ between control and treated animals. Animals immunized with BCG developed lymphocyte reactivity to tuberculin, which remained until the animals died. BCG was isolated from the spleen of one tumor-bearing animal.", "contents": "Immunization of Rous sarcoma virus-inoculated marmosets with BCG and transformed allogeneic cells. The effects of specific immunotherapy with allogeneic cells transformed by Schmidt-Ruppin Rous sarcoma virus (SR-RSV), of treatment with BCG, and of surgery on the growth of SR-RSV-induced sarcomas in white-lipped marmosets were studied. Tumor incidence, tumor progression, and survival did not differ between control and treated animals. Animals immunized with BCG developed lymphocyte reactivity to tuberculin, which remained until the animals died. BCG was isolated from the spleen of one tumor-bearing animal."} {"id": "PMID:163313", "title": "Effect of a normal serum protein absent from hepatoma-bearing animals on cell cultures.", "content": "The effect of a serum factor purified from normal rat serum on growth and incorporation of 3-H-thymidine and 3-H-leucine was investigated with the use of 3T3 and L cells. The factor was not present in serum of hepatoma-bearing animals at a time when the weight of the hepatomas was equal to or greater than liver weight. The factor disappeared gradually from the serum of hepatoma-bearing animals, and the disappearance was proportional to the increase in the size of the hepatomas. Diminished amounts of the factor could be detected as early as 10 days after hepatoma transplant, and the factor was absent at 30 days after hepatoma transplant from the serum of rats bearing hepatoma 7777. Medium supplemented with 5% normal rat serum supported incorporation of lavel into 3T3 and L cells and growth of these cells, as did medium supplemented with 10% calf serum. Serum from hepatoma-bearing animals was only approximately equal to 50% as efficient as normal rat serum in supporting growth and label incorporation. The addition of purified factor to the serum from hepatoma-bearing animals restored the ability of the serum to support growth and label incorporation to between 70 and 90% of that found with normal rat serum as a medium supplement. The factor also enhanced incorporation of 3-H-thymidine following release of 3T3 cells from contact inhibition.", "contents": "Effect of a normal serum protein absent from hepatoma-bearing animals on cell cultures. The effect of a serum factor purified from normal rat serum on growth and incorporation of 3-H-thymidine and 3-H-leucine was investigated with the use of 3T3 and L cells. The factor was not present in serum of hepatoma-bearing animals at a time when the weight of the hepatomas was equal to or greater than liver weight. The factor disappeared gradually from the serum of hepatoma-bearing animals, and the disappearance was proportional to the increase in the size of the hepatomas. Diminished amounts of the factor could be detected as early as 10 days after hepatoma transplant, and the factor was absent at 30 days after hepatoma transplant from the serum of rats bearing hepatoma 7777. Medium supplemented with 5% normal rat serum supported incorporation of lavel into 3T3 and L cells and growth of these cells, as did medium supplemented with 10% calf serum. Serum from hepatoma-bearing animals was only approximately equal to 50% as efficient as normal rat serum in supporting growth and label incorporation. The addition of purified factor to the serum from hepatoma-bearing animals restored the ability of the serum to support growth and label incorporation to between 70 and 90% of that found with normal rat serum as a medium supplement. The factor also enhanced incorporation of 3-H-thymidine following release of 3T3 cells from contact inhibition."} {"id": "PMID:163314", "title": "Effect of pyridoxine availability on the activity of serine dehydratase of normal liver, host liver, and three Morris hepatomas.", "content": "The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas \"5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas \"5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j (\"5123A), 3.5 (\"7316B), and 2.1 (\"7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas \"5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence.", "contents": "Effect of pyridoxine availability on the activity of serine dehydratase of normal liver, host liver, and three Morris hepatomas. The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas \"5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas \"5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j (\"5123A), 3.5 (\"7316B), and 2.1 (\"7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas \"5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence."} {"id": "PMID:163315", "title": "Adenosine-3',5'-cyclic monophosphate levels and adenosine-3',5'-cyclic monophosphate phosphodiesterase activity in metastasizing and nonmetastasizing rat mammary carcinomas.", "content": "The adenosine-3, 5-cyclic monophosphate phosphodiesterase (cPDE) activity in the homogenates of 6 spontaneously metastasizing, nonimmunogenic, glycocalyx-shedding rat mammary carcinomas (MT) was assayed and compared with four histologically and growth rate-matched nonmetastasizing, immunogenic MT. The levels of this enzyme were 2.5 times higher in the nonmetastasizing tumors. To rule out the possibility of the presence of inhibitor(s) or stimulator(s) of cPDE, homogenates from a nonmetastasizing and from a widely metastasizing tumor were mixed. cPDE from both nonmetastasizing and metastasizing MT showed two apparent Km and two corresponding Vmax. The activity of the enzyme at concentrations of 1 muM (low Km) and 100 muM (high Km) adenosine-3, 5-cyclic monophosphate (cAMP) decreased in parallel with increasing metastasizing capacity. About 50% of the low and the high Km cPDE was in the cytosol in both groups, whereas the rest was particulate. The proportion of low and high Km activity was similar in all the fractions except in the plasma membrane of the metastasizing tumors where the percent of low Km enzyme was three times higher than that of the high Km. The steady-state levels of cAMP were 1.3-2.0 times higher in the metastasizing tumors, inversely proportional to their cPDE activities.", "contents": "Adenosine-3',5'-cyclic monophosphate levels and adenosine-3',5'-cyclic monophosphate phosphodiesterase activity in metastasizing and nonmetastasizing rat mammary carcinomas. The adenosine-3, 5-cyclic monophosphate phosphodiesterase (cPDE) activity in the homogenates of 6 spontaneously metastasizing, nonimmunogenic, glycocalyx-shedding rat mammary carcinomas (MT) was assayed and compared with four histologically and growth rate-matched nonmetastasizing, immunogenic MT. The levels of this enzyme were 2.5 times higher in the nonmetastasizing tumors. To rule out the possibility of the presence of inhibitor(s) or stimulator(s) of cPDE, homogenates from a nonmetastasizing and from a widely metastasizing tumor were mixed. cPDE from both nonmetastasizing and metastasizing MT showed two apparent Km and two corresponding Vmax. The activity of the enzyme at concentrations of 1 muM (low Km) and 100 muM (high Km) adenosine-3, 5-cyclic monophosphate (cAMP) decreased in parallel with increasing metastasizing capacity. About 50% of the low and the high Km cPDE was in the cytosol in both groups, whereas the rest was particulate. The proportion of low and high Km activity was similar in all the fractions except in the plasma membrane of the metastasizing tumors where the percent of low Km enzyme was three times higher than that of the high Km. The steady-state levels of cAMP were 1.3-2.0 times higher in the metastasizing tumors, inversely proportional to their cPDE activities."} {"id": "PMID:163316", "title": "A new common marker for premalignant and malignant hepatocytes induced in the rat by chemical carcinogens.", "content": "A new common antigen, preneoplastic (PN), was found in every early and late hyperplastic nodule and in every primary hepatoma induced by N-2-fluorenylacetamide, ethionine, 3-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, or diethylnitrosamine in three strains of rats (CFN, F344, and BUF). It so far has not been found in normal adult rat liver, liver surrounding nodules or cancer, fetal liver, amniotic fluid, adult rat serum, sera from rats with hyperplastic nodules or primary hepatomas, or various normal rat tissues. Immunofluorescent staining indicated the PN antigen was present in the cytoplasm of hepatocytes in hyperplastic nodules and in primary hepatomas.", "contents": "A new common marker for premalignant and malignant hepatocytes induced in the rat by chemical carcinogens. A new common antigen, preneoplastic (PN), was found in every early and late hyperplastic nodule and in every primary hepatoma induced by N-2-fluorenylacetamide, ethionine, 3-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, or diethylnitrosamine in three strains of rats (CFN, F344, and BUF). It so far has not been found in normal adult rat liver, liver surrounding nodules or cancer, fetal liver, amniotic fluid, adult rat serum, sera from rats with hyperplastic nodules or primary hepatomas, or various normal rat tissues. Immunofluorescent staining indicated the PN antigen was present in the cytoplasm of hepatocytes in hyperplastic nodules and in primary hepatomas."} {"id": "PMID:163317", "title": "Anemia associated with feline leukemia virus infection in cats.", "content": "The types of anemia associated with natural and experimental feline leukemia virus (FeLV) infection in cats were investigated. In one experiment, 10 kittens were inoculated neonatally with Jarrett FeLV-1, an isolate of subgroup A; 6 developed anemia a few weeks later. This anemia was characterized by macrocytosis, normoblastosis, increased erythropoiesis in the bone marrow, and extramedullary hematopoiesis in the spleen. Anemia was transient and nonfatal and occurred before the onset of lympoid malignancy. The same type of anemia was also seen in 9 of 24 kittens inoculated with Jarrett FeLV-9 of subgroups A and B. A different form of anemai occurred in another experiment in which 10 kittens were inoculated with FeLV-C of subgroup C only. All 10 kittens developed a profound aplastic or erythroblastopenic anemia in which the bone marrow became depleted of erythroid tissue; all kittens died within 16 weeks, most as a direct result of anemia. In an experiment in which kittens were inoculated with FeLV-B of subgroup B only, no kitten showed anemia. Cats with naturally acquired, nonleukemic lymphosarcoma were also studied. Of 33 lymphosarcomas in which myelophthisis was excluded as a cause, 54% of the affected cats had anemia, the features of which were consistent with hemolytic origin. When virus could be grown from these lymphosarcomas, it was of subgroup A alone or a combination of A and B. With one exception, anemic cats had low or negative titers to feline oncornavirus-associated cell membrane antigens. Until more isolates have been tested, it is not known if the various hematologic changes reflected differences in the pathogenic effects of the subgroups of the virus or of types of strains within them.", "contents": "Anemia associated with feline leukemia virus infection in cats. The types of anemia associated with natural and experimental feline leukemia virus (FeLV) infection in cats were investigated. In one experiment, 10 kittens were inoculated neonatally with Jarrett FeLV-1, an isolate of subgroup A; 6 developed anemia a few weeks later. This anemia was characterized by macrocytosis, normoblastosis, increased erythropoiesis in the bone marrow, and extramedullary hematopoiesis in the spleen. Anemia was transient and nonfatal and occurred before the onset of lympoid malignancy. The same type of anemia was also seen in 9 of 24 kittens inoculated with Jarrett FeLV-9 of subgroups A and B. A different form of anemai occurred in another experiment in which 10 kittens were inoculated with FeLV-C of subgroup C only. All 10 kittens developed a profound aplastic or erythroblastopenic anemia in which the bone marrow became depleted of erythroid tissue; all kittens died within 16 weeks, most as a direct result of anemia. In an experiment in which kittens were inoculated with FeLV-B of subgroup B only, no kitten showed anemia. Cats with naturally acquired, nonleukemic lymphosarcoma were also studied. Of 33 lymphosarcomas in which myelophthisis was excluded as a cause, 54% of the affected cats had anemia, the features of which were consistent with hemolytic origin. When virus could be grown from these lymphosarcomas, it was of subgroup A alone or a combination of A and B. With one exception, anemic cats had low or negative titers to feline oncornavirus-associated cell membrane antigens. Until more isolates have been tested, it is not known if the various hematologic changes reflected differences in the pathogenic effects of the subgroups of the virus or of types of strains within them."} {"id": "PMID:163318", "title": "Evaluation of dye exclusion and colony inhibition techniques for detection of polyoma-specific, cell-mediated immunity.", "content": "Cellular immunity directed against polyoma virus-induced antigen was observed with C3H/HeJ splenic lymphoid cells from mice sensitized by a short-term immunization schedule with syngeneic polyoma 4198 and 4198V tumor cells. Polyoma specificity of the response was shown by demonstration that splenic cells from DBA/2J animals with polyoma virus-induced tumors were cytotoxic for the C3H 4198 and 4198V cells, but not for the L-M cell, another cell line of C3H origin. The polyoma-specific response in the syngeneic system was detectable with the dye exclusion assay but not with the colony inhibition procedure. Colony inhibition with the L-M cell was observed with sensitized lymphoid cells in both allogeneic and syngeneic systems.", "contents": "Evaluation of dye exclusion and colony inhibition techniques for detection of polyoma-specific, cell-mediated immunity. Cellular immunity directed against polyoma virus-induced antigen was observed with C3H/HeJ splenic lymphoid cells from mice sensitized by a short-term immunization schedule with syngeneic polyoma 4198 and 4198V tumor cells. Polyoma specificity of the response was shown by demonstration that splenic cells from DBA/2J animals with polyoma virus-induced tumors were cytotoxic for the C3H 4198 and 4198V cells, but not for the L-M cell, another cell line of C3H origin. The polyoma-specific response in the syngeneic system was detectable with the dye exclusion assay but not with the colony inhibition procedure. Colony inhibition with the L-M cell was observed with sensitized lymphoid cells in both allogeneic and syngeneic systems."} {"id": "PMID:163319", "title": "Potentiation of an adenovirus-associated virus by herpes simplex virus type-2-transformed cells.", "content": "The herpes simplex virus type-2 (HSV-2)-transformed cell line 333-8-9 was inoculated with adeno-virus-associated virus type 3 (AAV-3) and examined by immunofluorescent (FA) techniques for evidence of AAV-3 antigen synthesis. Antisera prepared against the three sodium dodecyl sulfate-dissociated structural polypeptides (VP-1, VP-2, and VP-3) of AAV-3 and against the whole AAV-3 virion were used as probes to search for AAV-3 FA-stainable antigens synthesized by these cells. The 333-8-9 cells inoculated with AAV-3 ALONE PRODUCED FA-stainable antigens detected by VP-1, VP-3, and whole virion antisera, but not by the VP-2 antiserum. Coinfection of AAV-3-INOCULATED 333-8-9 CELLS WITH EITHER ADENOVIRUS TYPE-2 (Ad.2) or herpes simplex virus type-1 (HSV-1) helper permitted the formation of FA-stainable antigens detected by all antisera, including the VP-2 antiserum. In contrast to 333-8-9 cells, BHK-21 cells failed to produce AAV-3 FA-stainable antigens when inoculated with AAV-3 alone; addition of either Ad.2 or HSV-1 helper led to formation of antigens detected by all VP and whole virion antisera. These results suggest that 333-8-9 cells enhance the formation of two of the three AAV-3 structural polypeptides and that this incomplete potentiation may be related to HSV-2 genetic material possessed by these cells.", "contents": "Potentiation of an adenovirus-associated virus by herpes simplex virus type-2-transformed cells. The herpes simplex virus type-2 (HSV-2)-transformed cell line 333-8-9 was inoculated with adeno-virus-associated virus type 3 (AAV-3) and examined by immunofluorescent (FA) techniques for evidence of AAV-3 antigen synthesis. Antisera prepared against the three sodium dodecyl sulfate-dissociated structural polypeptides (VP-1, VP-2, and VP-3) of AAV-3 and against the whole AAV-3 virion were used as probes to search for AAV-3 FA-stainable antigens synthesized by these cells. The 333-8-9 cells inoculated with AAV-3 ALONE PRODUCED FA-stainable antigens detected by VP-1, VP-3, and whole virion antisera, but not by the VP-2 antiserum. Coinfection of AAV-3-INOCULATED 333-8-9 CELLS WITH EITHER ADENOVIRUS TYPE-2 (Ad.2) or herpes simplex virus type-1 (HSV-1) helper permitted the formation of FA-stainable antigens detected by all antisera, including the VP-2 antiserum. In contrast to 333-8-9 cells, BHK-21 cells failed to produce AAV-3 FA-stainable antigens when inoculated with AAV-3 alone; addition of either Ad.2 or HSV-1 helper led to formation of antigens detected by all VP and whole virion antisera. These results suggest that 333-8-9 cells enhance the formation of two of the three AAV-3 structural polypeptides and that this incomplete potentiation may be related to HSV-2 genetic material possessed by these cells."} {"id": "PMID:163320", "title": "Biochemical properties of simian virus 40-transformed 3T3 cell mitochondria.", "content": "Mitrochondria isolated from simian virus 40-transformed 3T3 and nontransformed 3T3 cells were compared by various biochemical criteria. Transformed and nontransformed cell mitochondria had identical densities in linear sucrose and discontinuous bovine serum albumin gradients. The activities of several mitochondria-specific enzymes including cytochrome oxidase, adenylate kinase, nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase, and NADH oxidase were similar in both cell types. However, the activity of the mitochondrial outer membrane enzyme, monoamine oxidase. In the virus-transformed cell mitochondria was reduced to 50% of that in nontransformed cell mitochondria.", "contents": "Biochemical properties of simian virus 40-transformed 3T3 cell mitochondria. Mitrochondria isolated from simian virus 40-transformed 3T3 and nontransformed 3T3 cells were compared by various biochemical criteria. Transformed and nontransformed cell mitochondria had identical densities in linear sucrose and discontinuous bovine serum albumin gradients. The activities of several mitochondria-specific enzymes including cytochrome oxidase, adenylate kinase, nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase, and NADH oxidase were similar in both cell types. However, the activity of the mitochondrial outer membrane enzyme, monoamine oxidase. In the virus-transformed cell mitochondria was reduced to 50% of that in nontransformed cell mitochondria."} {"id": "PMID:163321", "title": "Type-C virus particles in placenta of the cottontop marmoset (Saguinus oedipus).", "content": "Electron microscopy of near-term placentas of two cottontop marmosets (Saguinus oedipus) revealed, in one placenta, the presence of budding and mature C-type virus particles associated with the basal trophoblast. The particles were morphologically similar to those observed by other investigators in placentas of other primate species.", "contents": "Type-C virus particles in placenta of the cottontop marmoset (Saguinus oedipus). Electron microscopy of near-term placentas of two cottontop marmosets (Saguinus oedipus) revealed, in one placenta, the presence of budding and mature C-type virus particles associated with the basal trophoblast. The particles were morphologically similar to those observed by other investigators in placentas of other primate species."} {"id": "PMID:163322", "title": "B-cell origin of hamster lymphoid tumors induced by simian virus 40.", "content": "Two lymphoid neoplasms induced by simian virus 40 (SV40) in Syrian hamsters were analyzed for lymphocyte characteristics. The hymphocytes from both tumors contained membrane-bound Ig that was exclusively of 7Sgamma2 class. Furthermore, neither lymphoid tumor had a complement receptor. Thus both tumors oringinated from a particular B-cell population, which suggests that this B-cell type is associated with an SV40 receptor.", "contents": "B-cell origin of hamster lymphoid tumors induced by simian virus 40. Two lymphoid neoplasms induced by simian virus 40 (SV40) in Syrian hamsters were analyzed for lymphocyte characteristics. The hymphocytes from both tumors contained membrane-bound Ig that was exclusively of 7Sgamma2 class. Furthermore, neither lymphoid tumor had a complement receptor. Thus both tumors oringinated from a particular B-cell population, which suggests that this B-cell type is associated with an SV40 receptor."} {"id": "PMID:163324", "title": "Elevated immunofluorescence antibody titers to several herpesviruses in Burkitt's lymphoma patients: are high titers unique?", "content": "Antibody titers for viral capsid antigens of all four human herpesviruses were measured by immunofluorescence in the sera of 16 Burkitt's lymphoma (BL) PATIENTS, 16 AGE-, SEX-, AND LOCALITY-MATCHED CONTROLS, AND 136 FAMILY MEMBERS FROM THE West Nile District of Uganda. Among family members, titers greater than 1:4 were found in 98% for herpes simplex virus (HSV), 86% for varicella-zoster virus (VZV), 100% FOR CYTOMEGALOVIRUS (CMV), AND 94% FOR Epstein-Barr (EBV). Titers in patients averaged approximately equal to 2 logs (fourfold) higher than those in matched controls for EBV, VZV, and CMV (P EQUALS 0.001); titers for HSV were only slightly higher in cancer patients. The mothers of patients had someuhat higher EBV titers (0.05 smaller than or equal to P SMALLER THAN OR EQUAL TO 0.01) than the mothers of controls, but no other differences between patient and control families were found. By immunofluorescence, a method which apparently has not been used for all four human herpesviruses in BL patients, the patients had elevated antibody titers not only to EBV but also to CMV and VZV. The elevated titers to three of the four human herpesviruses were not due to serologic cross reactions.", "contents": "Elevated immunofluorescence antibody titers to several herpesviruses in Burkitt's lymphoma patients: are high titers unique? Antibody titers for viral capsid antigens of all four human herpesviruses were measured by immunofluorescence in the sera of 16 Burkitt's lymphoma (BL) PATIENTS, 16 AGE-, SEX-, AND LOCALITY-MATCHED CONTROLS, AND 136 FAMILY MEMBERS FROM THE West Nile District of Uganda. Among family members, titers greater than 1:4 were found in 98% for herpes simplex virus (HSV), 86% for varicella-zoster virus (VZV), 100% FOR CYTOMEGALOVIRUS (CMV), AND 94% FOR Epstein-Barr (EBV). Titers in patients averaged approximately equal to 2 logs (fourfold) higher than those in matched controls for EBV, VZV, and CMV (P EQUALS 0.001); titers for HSV were only slightly higher in cancer patients. The mothers of patients had someuhat higher EBV titers (0.05 smaller than or equal to P SMALLER THAN OR EQUAL TO 0.01) than the mothers of controls, but no other differences between patient and control families were found. By immunofluorescence, a method which apparently has not been used for all four human herpesviruses in BL patients, the patients had elevated antibody titers not only to EBV but also to CMV and VZV. The elevated titers to three of the four human herpesviruses were not due to serologic cross reactions."} {"id": "PMID:163325", "title": "Unexpected high incidence of primary liver cancer in Geneva, Switzerland.", "content": "The age-standardized incidence rate of primary liver cancer (PLC) in Geneva was 9.7 per 100,000 in males, a figure four or five times higher than incidence rates reported elsewhere in Europe . These PLC's were often associated with cirrhosis and alcoholism. This indicated that the toll of PLC related to alcoholism and to alcoholic cirrhosis may be greater than anticipated.", "contents": "Unexpected high incidence of primary liver cancer in Geneva, Switzerland. The age-standardized incidence rate of primary liver cancer (PLC) in Geneva was 9.7 per 100,000 in males, a figure four or five times higher than incidence rates reported elsewhere in Europe . These PLC's were often associated with cirrhosis and alcoholism. This indicated that the toll of PLC related to alcoholism and to alcoholic cirrhosis may be greater than anticipated."} {"id": "PMID:163326", "title": "Induction of Epstein-Barr virus-associated nuclear antigen during in vitro transformation of human lymphoid cells.", "content": "Human lymphoid cells isolated from the peripheral blood of adults, from cord blood, and from fetal liver, spleen, bone marrow, and thymus were cultivated with or without a cell-free preparation of Epstein-Barr virus (EBV) with demonstrated transforming activity. The cultures were examined for the EBV-associated nuclear antigen (EBNA) and for transfromation into permanent lymphoblastoid cell lines (LCL). EBNA, seen only in cultures that had received exogenous EBV, was detected between days 1 and 6 after addition of EBV, most frequently on day 3. EBNA-positive cells had a lymphoblastoid appearance. Transformation into established LCL became apparent between days 12 and 19. The addition of pokeweed mitogen to cultures containing EBV enhanced the development of EBNA, whereas phytohemagglutinin or concanavalin A had no such effect. Neither EBNA nor transfomration was observed in lymphoid cells from fetal thymus. In fetal spleen, bone marrow, and liver cells, EBV regularly induced EBNA and LCL transformation.", "contents": "Induction of Epstein-Barr virus-associated nuclear antigen during in vitro transformation of human lymphoid cells. Human lymphoid cells isolated from the peripheral blood of adults, from cord blood, and from fetal liver, spleen, bone marrow, and thymus were cultivated with or without a cell-free preparation of Epstein-Barr virus (EBV) with demonstrated transforming activity. The cultures were examined for the EBV-associated nuclear antigen (EBNA) and for transfromation into permanent lymphoblastoid cell lines (LCL). EBNA, seen only in cultures that had received exogenous EBV, was detected between days 1 and 6 after addition of EBV, most frequently on day 3. EBNA-positive cells had a lymphoblastoid appearance. Transformation into established LCL became apparent between days 12 and 19. The addition of pokeweed mitogen to cultures containing EBV enhanced the development of EBNA, whereas phytohemagglutinin or concanavalin A had no such effect. Neither EBNA nor transfomration was observed in lymphoid cells from fetal thymus. In fetal spleen, bone marrow, and liver cells, EBV regularly induced EBNA and LCL transformation."} {"id": "PMID:163327", "title": "Isolation of a B-tropic type-C virus from reticulum cell neoplasms induced in BALB/c mice by SJL/J type-C virus.", "content": "D1-murine leukemia virus (MuLV), an N-tropic type-C virus isolated from a spontaneous reticulum cell neoplasm, type B (RCN-B) of an SJL/J mouse was propagated in NIH Swiss mouse embryo cell cultures. When injected into BALB/c mice 1 day after neonatal thymectomy, 30% of the inoculated mice developed RCN-B in 5 months, whereas none of the uninoculated controls did. From the spleen and lymph node extracts of all RCN-B-bearing mice tested, B-tropic type-C viruses (designated E1-MuLV) were isolated in high titers (10-5 minus 10-6 XC plaque-forming units/ml). Only low titers (10-1 minus 10-2 XC plaque-forming units/ml) of N- or B-tropic viruses were isolated from those thymectomized mice, inoculated but nontumorous, whereas only N-tropic viruses were detected in the uninoculated thymectomized mice. No virus was isolated from the nonthymectomized, untreated controls. Antigenically, the viral envelope antigen (VEA) of E1-MuLV was distinct from those of DU-MuLV, xVEA, or Gross-VEA, but some cross reaction with AKR-MuLV-VEA was observed. The relationship of D1-MuLV to E1-MuVL with respect to oncogenesis and viral genome activation was discussed.", "contents": "Isolation of a B-tropic type-C virus from reticulum cell neoplasms induced in BALB/c mice by SJL/J type-C virus. D1-murine leukemia virus (MuLV), an N-tropic type-C virus isolated from a spontaneous reticulum cell neoplasm, type B (RCN-B) of an SJL/J mouse was propagated in NIH Swiss mouse embryo cell cultures. When injected into BALB/c mice 1 day after neonatal thymectomy, 30% of the inoculated mice developed RCN-B in 5 months, whereas none of the uninoculated controls did. From the spleen and lymph node extracts of all RCN-B-bearing mice tested, B-tropic type-C viruses (designated E1-MuLV) were isolated in high titers (10-5 minus 10-6 XC plaque-forming units/ml). Only low titers (10-1 minus 10-2 XC plaque-forming units/ml) of N- or B-tropic viruses were isolated from those thymectomized mice, inoculated but nontumorous, whereas only N-tropic viruses were detected in the uninoculated thymectomized mice. No virus was isolated from the nonthymectomized, untreated controls. Antigenically, the viral envelope antigen (VEA) of E1-MuLV was distinct from those of DU-MuLV, xVEA, or Gross-VEA, but some cross reaction with AKR-MuLV-VEA was observed. The relationship of D1-MuLV to E1-MuVL with respect to oncogenesis and viral genome activation was discussed."} {"id": "PMID:163328", "title": "Chromosome aberrations in Syrian hamster embryo cells transformed after exposure to ultraviolet-irradiated herpes simplex virus type 1 or 2.", "content": "Six Syrian hamster embryo cell lines (14-012-8-1, KOS-6-1, 333-8-9, 333-2-29, MS-4-1, FR-6-1), developed after exposure of primary cultures to different strains of UV-irradiated herpes simplex virus (HSV) type 1 or 2, were analyzed for chromosome aberrations. All the cell lines showed chromosome stability (number of chromosomes were maintained within a narrow range of variation in the diploid region) and a low incidence of polyploids, endoreduplications, and metaphases with pulveration or extensively fragmented chromosomes. The cell lines, passaged over long periods of time in vitro, developed marker chromosomes that suggested a clonal-type evolution of the cell populations. Two cell lines, 333-8-9 and 14-012-8-1, showed two different marker chromosomes with large heterochromatic regions. Chromosomes with abnormal heterochromatic regions, which often appeared like prominent secondary constrictions, were found in all the cell lines we examined. The level of chromosome breakage was low in all the cell lines except the highly tumorigenic cell line 333-2-29, which had a high incidence of cells with single or double chromatinic bodies. The abnormal heterochromatic regions that occurred on marker chromosomes and prominent secondary constrictions were interpreted as a possible chromosomal effect of the HSV. The karyotypic stability and low incidence of open breaks might have been the result of UV irradiation of the HSV.", "contents": "Chromosome aberrations in Syrian hamster embryo cells transformed after exposure to ultraviolet-irradiated herpes simplex virus type 1 or 2. Six Syrian hamster embryo cell lines (14-012-8-1, KOS-6-1, 333-8-9, 333-2-29, MS-4-1, FR-6-1), developed after exposure of primary cultures to different strains of UV-irradiated herpes simplex virus (HSV) type 1 or 2, were analyzed for chromosome aberrations. All the cell lines showed chromosome stability (number of chromosomes were maintained within a narrow range of variation in the diploid region) and a low incidence of polyploids, endoreduplications, and metaphases with pulveration or extensively fragmented chromosomes. The cell lines, passaged over long periods of time in vitro, developed marker chromosomes that suggested a clonal-type evolution of the cell populations. Two cell lines, 333-8-9 and 14-012-8-1, showed two different marker chromosomes with large heterochromatic regions. Chromosomes with abnormal heterochromatic regions, which often appeared like prominent secondary constrictions, were found in all the cell lines we examined. The level of chromosome breakage was low in all the cell lines except the highly tumorigenic cell line 333-2-29, which had a high incidence of cells with single or double chromatinic bodies. The abnormal heterochromatic regions that occurred on marker chromosomes and prominent secondary constrictions were interpreted as a possible chromosomal effect of the HSV. The karyotypic stability and low incidence of open breaks might have been the result of UV irradiation of the HSV."} {"id": "PMID:163330", "title": "Blood group MN antigens and precursors in normal and malignant human breast glandular tissue.", "content": "Blood group M and N active substances were demonstrated in human mammary gland tissue in both benign and malignant lesions. The precursor T (Thomsen-Friedenreich) antigen occurred only in cancerous tissue, where it was found regularly in the 15 gross cancers tested. The precursor Tn antigen also was found regularly in cancerous breast tissue; Both antigens were reactive in breasts with in situ carcinoma. The T antigen was not demonstrable in the 6 benign mammary glands studied; similarly, the Tn antigen was unmasked by sialidase treatment of healthy breast tissues. Anti-T antibody, present in all human sera, was severely depressed in many breast cancer patients compared to controls.", "contents": "Blood group MN antigens and precursors in normal and malignant human breast glandular tissue. Blood group M and N active substances were demonstrated in human mammary gland tissue in both benign and malignant lesions. The precursor T (Thomsen-Friedenreich) antigen occurred only in cancerous tissue, where it was found regularly in the 15 gross cancers tested. The precursor Tn antigen also was found regularly in cancerous breast tissue; Both antigens were reactive in breasts with in situ carcinoma. The T antigen was not demonstrable in the 6 benign mammary glands studied; similarly, the Tn antigen was unmasked by sialidase treatment of healthy breast tissues. Anti-T antibody, present in all human sera, was severely depressed in many breast cancer patients compared to controls."} {"id": "PMID:163331", "title": "A quantitative autoradiographic study of nucleolus-associated RNA and DNA synthesis during the eclipse phase in Rous sarcoma virus-infected chicken fibroblasts.", "content": "Functional and morphologic differences between the sensitivity of nucleoli of Rous sarcoma virus-transformed cells and that of newly infected cells to the action of actinomycin D (AD) have been demonstrated by quantitative light and electron microscope autoradiography and utilized to investigate the function of the nucleolus in the early stages of infection. After a pulse exposure to low doses of AD, increased RNA synthesis is induced within 80 minutes in the fibrillar portion of the nucleolus by infection. A concomitant increase in the retention of tritiated AD in the nucleolus and a quantitative redistribution of intranuclear and cytoplasmic DNA label are interpreted as evidence for a virus-induced amplification of the binding sites of AD in nucleolar chromatin.", "contents": "A quantitative autoradiographic study of nucleolus-associated RNA and DNA synthesis during the eclipse phase in Rous sarcoma virus-infected chicken fibroblasts. Functional and morphologic differences between the sensitivity of nucleoli of Rous sarcoma virus-transformed cells and that of newly infected cells to the action of actinomycin D (AD) have been demonstrated by quantitative light and electron microscope autoradiography and utilized to investigate the function of the nucleolus in the early stages of infection. After a pulse exposure to low doses of AD, increased RNA synthesis is induced within 80 minutes in the fibrillar portion of the nucleolus by infection. A concomitant increase in the retention of tritiated AD in the nucleolus and a quantitative redistribution of intranuclear and cytoplasmic DNA label are interpreted as evidence for a virus-induced amplification of the binding sites of AD in nucleolar chromatin."} {"id": "PMID:163332", "title": "Effect of simian virus 40 subcutaneous tumors on circulating lipids and lipoproteins in the Syrian hamster.", "content": "Circulating lipid levels and lipoprotein patterns in the Syrian hamster were determined at various times after subcutaneous inoculation with simian virus 40 (SV40) strain F, strain A-2895, or Fortner melanoma tumor cells. SV40 F tumors induced a rapid triphasic elevation of serum total lipids through inhibition of prebeta lipoprotein catabolism. Alpha lipoprotein levels declined in proportion to tumor mass. Liver wet weight and total lipid content increased significantly, but a normal rate of 3H-glycerol incorporation into polyanion precipitable (prebeta) serum lipoprotein was maintained. Determination of serum endogenous lipase, lecithin:cholesterol acyltransferase (LCAT), and cholinesterase activities indicated that these enzymes were not primarily responsible for the tumor-induced hyperlipidemia. Tumor-bearing animals also had selectively increased rates of protein and lipid excretion into the urine, with no evidence of gross hepatocellular or kidney damage. Growth of SV40 A-2895 tumors in hamsters resulted in a large increase in the rate of prebeta lipoprotein synthesis and degradation. Circulating prebeta lipoprotein levels were elevated much later in these animals, subsequent to a marked decrease in LCAT activity. Quite different results were obtained with Fortner melanoma, even large tumors having only a moderate effect on serum total lipid levels and lipoprotein patterns in the Syrian hamster.", "contents": "Effect of simian virus 40 subcutaneous tumors on circulating lipids and lipoproteins in the Syrian hamster. Circulating lipid levels and lipoprotein patterns in the Syrian hamster were determined at various times after subcutaneous inoculation with simian virus 40 (SV40) strain F, strain A-2895, or Fortner melanoma tumor cells. SV40 F tumors induced a rapid triphasic elevation of serum total lipids through inhibition of prebeta lipoprotein catabolism. Alpha lipoprotein levels declined in proportion to tumor mass. Liver wet weight and total lipid content increased significantly, but a normal rate of 3H-glycerol incorporation into polyanion precipitable (prebeta) serum lipoprotein was maintained. Determination of serum endogenous lipase, lecithin:cholesterol acyltransferase (LCAT), and cholinesterase activities indicated that these enzymes were not primarily responsible for the tumor-induced hyperlipidemia. Tumor-bearing animals also had selectively increased rates of protein and lipid excretion into the urine, with no evidence of gross hepatocellular or kidney damage. Growth of SV40 A-2895 tumors in hamsters resulted in a large increase in the rate of prebeta lipoprotein synthesis and degradation. Circulating prebeta lipoprotein levels were elevated much later in these animals, subsequent to a marked decrease in LCAT activity. Quite different results were obtained with Fortner melanoma, even large tumors having only a moderate effect on serum total lipid levels and lipoprotein patterns in the Syrian hamster."} {"id": "PMID:163333", "title": "Inhibition of the cellular immune response to simian virus 40 tumor cells in tumor-bearing and tumor-immune mice by concanavalin A.", "content": "The effects of in vivo-administered concanavalin A (Con A) on the kinetics of the primary and secondary cellular immune responses to simian virus 40-transformed tumor cells were investigated in BALB/c mice. Either a single initial dose of 400 mug Con A or daily doses of 50 mug depressed the cell-mediated immune response to tumor cells during the progressive growth of tumors, as determined by a radioisotopic foot-pad assay. The immune depression correlated with an increase in ultimate tumor weight. Similarly, Con A suppressed the antitumor cellular immune response in tumor-immune animals. Immune reactivity returned within 6 days after a single injection of 400 mug Con. Continuous administration 50 mug Con A resulted in a gradual decline in antitumor cellular immune responsiveness, which reached a plateau by the 5th day. Splenic lymphocytes from Con A-treated, immune mice failed to elicit a local adoptive transfer reaction; their immune responsiveness tended to return after incubation with alpha-methyl-D-pyranosyl sugars.", "contents": "Inhibition of the cellular immune response to simian virus 40 tumor cells in tumor-bearing and tumor-immune mice by concanavalin A. The effects of in vivo-administered concanavalin A (Con A) on the kinetics of the primary and secondary cellular immune responses to simian virus 40-transformed tumor cells were investigated in BALB/c mice. Either a single initial dose of 400 mug Con A or daily doses of 50 mug depressed the cell-mediated immune response to tumor cells during the progressive growth of tumors, as determined by a radioisotopic foot-pad assay. The immune depression correlated with an increase in ultimate tumor weight. Similarly, Con A suppressed the antitumor cellular immune response in tumor-immune animals. Immune reactivity returned within 6 days after a single injection of 400 mug Con. Continuous administration 50 mug Con A resulted in a gradual decline in antitumor cellular immune responsiveness, which reached a plateau by the 5th day. Splenic lymphocytes from Con A-treated, immune mice failed to elicit a local adoptive transfer reaction; their immune responsiveness tended to return after incubation with alpha-methyl-D-pyranosyl sugars."} {"id": "PMID:163334", "title": "Properties of a chicken lymphoblastoid cell line from Marek's disease tumor.", "content": "Properties of a chicken lymphoblastoid cell line (MSB-1) from a Marek's disease tumor were studied. The cell line grew well at 41 degrees C in medium RPMI-1640 supplemented with 10% bovine fetal serum and had a doubling time of 8-12 hours. Cells grown in stationary suspension culture did not attach to the vessel and had the morphology of typical lymphoblasts. At 37 degrees C, the cell line grew initially but ceased to divide after several subcultures. In the subcultures maintained for 48-72 hours, 1-2% of the cells produced Marek's disease virus (MDV)-specific intracellular and mambrane antigens and contained herpesvirus particles when examined by the electron microscope. Cocultivation of these cells with duck or chicken embryo fibroblast cultures resulted in transfer of infection and production of microplaques typical of MDV. Peripheral nerve lesions and lymphoid tumors characteristic of Marek's disease were caused by inoculation of susceptible chicks with MSB-1 cells or duck cells infected with strain BC-1 of MDV recovered from the MSB-1 cell line. No specific tumors were produced at the site of inoculation, and infection was readily transmitted to cagemates. Tumors were also produced in the skeletal muscles and seemed to be largely virus induced. MSB-1 cell line was free of C-type virus particles.", "contents": "Properties of a chicken lymphoblastoid cell line from Marek's disease tumor. Properties of a chicken lymphoblastoid cell line (MSB-1) from a Marek's disease tumor were studied. The cell line grew well at 41 degrees C in medium RPMI-1640 supplemented with 10% bovine fetal serum and had a doubling time of 8-12 hours. Cells grown in stationary suspension culture did not attach to the vessel and had the morphology of typical lymphoblasts. At 37 degrees C, the cell line grew initially but ceased to divide after several subcultures. In the subcultures maintained for 48-72 hours, 1-2% of the cells produced Marek's disease virus (MDV)-specific intracellular and mambrane antigens and contained herpesvirus particles when examined by the electron microscope. Cocultivation of these cells with duck or chicken embryo fibroblast cultures resulted in transfer of infection and production of microplaques typical of MDV. Peripheral nerve lesions and lymphoid tumors characteristic of Marek's disease were caused by inoculation of susceptible chicks with MSB-1 cells or duck cells infected with strain BC-1 of MDV recovered from the MSB-1 cell line. No specific tumors were produced at the site of inoculation, and infection was readily transmitted to cagemates. Tumors were also produced in the skeletal muscles and seemed to be largely virus induced. MSB-1 cell line was free of C-type virus particles."} {"id": "PMID:163335", "title": "Estrogen-dependent in vitro stimulation of RNA synthesis in hormone-dependent mammary tumors of the rat.", "content": "Incubation of estradiol in vitro at 25 degrees C with homogenates of carcinogen-induced mammary tumors of ovariectomized rats stimulated the magnesium-dependent RNA polymerase activity of nuclei of the hormone-dependent (HD) (regressing) tumors, but had no effect on this activity in nuclei of hormone-independent (HI) (growing) tumors. Furthermore, recombination of the nuclei and cytosol fractions of HD and HI tumors indicated that the in vitro effect of estradiol on subsequent tumor nuclear RNA synthesis required the estrogen receptor-containing cytosol but was specific to nuclei of the HD tumor. This constituted the first direct in vitro effect of estrogen on a specific biochemical process in an HD mammary tumor.", "contents": "Estrogen-dependent in vitro stimulation of RNA synthesis in hormone-dependent mammary tumors of the rat. Incubation of estradiol in vitro at 25 degrees C with homogenates of carcinogen-induced mammary tumors of ovariectomized rats stimulated the magnesium-dependent RNA polymerase activity of nuclei of the hormone-dependent (HD) (regressing) tumors, but had no effect on this activity in nuclei of hormone-independent (HI) (growing) tumors. Furthermore, recombination of the nuclei and cytosol fractions of HD and HI tumors indicated that the in vitro effect of estradiol on subsequent tumor nuclear RNA synthesis required the estrogen receptor-containing cytosol but was specific to nuclei of the HD tumor. This constituted the first direct in vitro effect of estrogen on a specific biochemical process in an HD mammary tumor."} {"id": "PMID:163336", "title": "Spontaneous lymphoma associated with Herpesvirus saimiri in owl monkeys.", "content": "Two cases of lymphoma and one case of lymphoproliferative disease were found in a group of 7 owl monkeys imported into our colony as a single group. Herpesvirus saimiri (HVS) was isolated from the tumor cells of 1 lymphoma by cocultivation and from kidney cell cultures from the monkey with lymphoproliferative disease. Antibody to HVS was found in serum samples from 2 monkeys positive for HVS but not in the sera from the 4 clinically normal monkeys. Antibody to Epstein-Barr virus-infected cells was also found in the serum from the animal with lymphoma.", "contents": "Spontaneous lymphoma associated with Herpesvirus saimiri in owl monkeys. Two cases of lymphoma and one case of lymphoproliferative disease were found in a group of 7 owl monkeys imported into our colony as a single group. Herpesvirus saimiri (HVS) was isolated from the tumor cells of 1 lymphoma by cocultivation and from kidney cell cultures from the monkey with lymphoproliferative disease. Antibody to HVS was found in serum samples from 2 monkeys positive for HVS but not in the sera from the 4 clinically normal monkeys. Antibody to Epstein-Barr virus-infected cells was also found in the serum from the animal with lymphoma."} {"id": "PMID:163337", "title": "Virus envelope markers in mammalian tropism of avian RNA tumor viruses.", "content": "Pseudotypes of vesicular stomatitis virus were prepared with avian sarcoma viruses and avian leukemia viruses representing five different subgroups. These pseudotypes display a host range restricted to that of the avian tumor virus when assayed on avian cells and are neutralized by subgroup-specific antisera. The efficiency of penetration of mammalian cells was assayed by using these vesicular stomatitis virus pseudotypes. Pseudotypes of avian tumor viruses belonging to subgroup D and of B77 virus were able to plate on mammalian cells with a high efficiency, whereas pseudotypes of other strains were not. The efficiency of penetration of the vesicular stomatitis virus pseudotypes was 10-2-to 10-3-fold higher than the efficiency of transformation of the corresponding avian tumor virus strain assayed on mammalian cells, suggesting that there are postpenetration blocks to the expression of transformation in these cells.", "contents": "Virus envelope markers in mammalian tropism of avian RNA tumor viruses. Pseudotypes of vesicular stomatitis virus were prepared with avian sarcoma viruses and avian leukemia viruses representing five different subgroups. These pseudotypes display a host range restricted to that of the avian tumor virus when assayed on avian cells and are neutralized by subgroup-specific antisera. The efficiency of penetration of mammalian cells was assayed by using these vesicular stomatitis virus pseudotypes. Pseudotypes of avian tumor viruses belonging to subgroup D and of B77 virus were able to plate on mammalian cells with a high efficiency, whereas pseudotypes of other strains were not. The efficiency of penetration of the vesicular stomatitis virus pseudotypes was 10-2-to 10-3-fold higher than the efficiency of transformation of the corresponding avian tumor virus strain assayed on mammalian cells, suggesting that there are postpenetration blocks to the expression of transformation in these cells."} {"id": "PMID:163338", "title": "Products of complementation between temperature-sensitive mutants of simian virus 40.", "content": "Temperature-sensitive mutants of the D complementation group of simian virus 40 exhibit delayed complementation. Analysis of the thermal stability, kinetic profiles in temperature shift experiments, and progeny of complementation have led to the hypothesis that delayed complementation is not true complementation, but the result of a very low level of leakiness, followed by phenotypic mixing of the progeny D mutants. This hypothesis is consistent with the proposal that D mutants are defective in uncoating. In the course of these experiments, it was observed that fresh medium suppresses the growth of D mutants at the restrictive temperature.", "contents": "Products of complementation between temperature-sensitive mutants of simian virus 40. Temperature-sensitive mutants of the D complementation group of simian virus 40 exhibit delayed complementation. Analysis of the thermal stability, kinetic profiles in temperature shift experiments, and progeny of complementation have led to the hypothesis that delayed complementation is not true complementation, but the result of a very low level of leakiness, followed by phenotypic mixing of the progeny D mutants. This hypothesis is consistent with the proposal that D mutants are defective in uncoating. In the course of these experiments, it was observed that fresh medium suppresses the growth of D mutants at the restrictive temperature."} {"id": "PMID:163339", "title": "DNA infectivity and the induction of host DNA synthesis with temperature-sensitive mutants of simian virus 40.", "content": "Host DNA synthesis is induced when CV-1 (monkey kidney) cell cultures are infected at 40 C with wild-type virions or with temperature-sensitive Simian virus 40 mutants of the \"early\" complementation group A. Host DNA synthesis is not induced when cultures are infected with mutants of the late complementation group D. The simplest explanation for these observations, that induction depends not upon the expression of some early gene function but rather on the presence of an active D protein in the infecting virion, has been examined. Indirect experiments suggest that this explanation is not correct. Moreover, the induction of host DNA synthesis is impaired when cultures are infected with mutants of the A group at 42.5 C rather than 40 C, suggesting that the A function may be responsible for host induction. The inability of D virions to induce host DNA synthesis may reflect their inability to \"uncoat\" at 40C.", "contents": "DNA infectivity and the induction of host DNA synthesis with temperature-sensitive mutants of simian virus 40. Host DNA synthesis is induced when CV-1 (monkey kidney) cell cultures are infected at 40 C with wild-type virions or with temperature-sensitive Simian virus 40 mutants of the \"early\" complementation group A. Host DNA synthesis is not induced when cultures are infected with mutants of the late complementation group D. The simplest explanation for these observations, that induction depends not upon the expression of some early gene function but rather on the presence of an active D protein in the infecting virion, has been examined. Indirect experiments suggest that this explanation is not correct. Moreover, the induction of host DNA synthesis is impaired when cultures are infected with mutants of the A group at 42.5 C rather than 40 C, suggesting that the A function may be responsible for host induction. The inability of D virions to induce host DNA synthesis may reflect their inability to \"uncoat\" at 40C."} {"id": "PMID:163340", "title": "Molecular weight of RNA subunits of Rous sarcoma virus determined by electron microscopy.", "content": "Secondary cultures of chicken embryo fibroblasts were infected with the Schmidt Ruppin strain of Rous sarcoma virus (RSV). Five days after infection, the medium was replaced at 2-h intervals with phosphate-free Eagle medium containing 50 muCi of [32P]orthophosphate per ml. Virus was collected by centrifugation, and the RNA was extracted and denatured with dimethyl sulfoxide, and the 33S subunit RNA was isolated by sucrose gradient centrifugation. The molecular weight of the RSV subunit RNA was determined by length measurement in the electron microscope, by using bacteriophage MS2 RNA as a length marker. Molecules of between 2.5 and 3.3 mum in length made up over 50% of the subunit RNA preparation. In this paper, we define RSV RNA subunits as that RNA released from the 70S RNA complex by dimethyl sulfoxide treatment, which sediments as a peak at 33S. Assuming the molecular weight of MS2 RNA to be 1.2 times 10-6, we calculate the molecular weight of RSV subunit RNA to be 3.12 times 10-6 plus or minus 0.25 times 10-6.", "contents": "Molecular weight of RNA subunits of Rous sarcoma virus determined by electron microscopy. Secondary cultures of chicken embryo fibroblasts were infected with the Schmidt Ruppin strain of Rous sarcoma virus (RSV). Five days after infection, the medium was replaced at 2-h intervals with phosphate-free Eagle medium containing 50 muCi of [32P]orthophosphate per ml. Virus was collected by centrifugation, and the RNA was extracted and denatured with dimethyl sulfoxide, and the 33S subunit RNA was isolated by sucrose gradient centrifugation. The molecular weight of the RSV subunit RNA was determined by length measurement in the electron microscope, by using bacteriophage MS2 RNA as a length marker. Molecules of between 2.5 and 3.3 mum in length made up over 50% of the subunit RNA preparation. In this paper, we define RSV RNA subunits as that RNA released from the 70S RNA complex by dimethyl sulfoxide treatment, which sediments as a peak at 33S. Assuming the molecular weight of MS2 RNA to be 1.2 times 10-6, we calculate the molecular weight of RSV subunit RNA to be 3.12 times 10-6 plus or minus 0.25 times 10-6."} {"id": "PMID:163341", "title": "Electron microscope localization of a protein bound near the origin of simian virus 40 DNA replication.", "content": "A salt-stable complex of protein and viral DNA obtained from Simian virus 40 (SV40)-infected monkey cells or mature SV40 virions has a novel structure. When viewed by high resolution electron microscopy, the circular SV40 DNA molecule has bound to it one to three globular protein \"knobs\". Using ecoRI and hpaII restriction endonucleases, each of which can cleave SV40 DNA once at a known location (10, 11, 12, 14), the bound protein can be localized at 0.7 plus or minis 0.05 on the SV40 DNA physical map (SV40 fractional length, clockwise from the ecoRI endonuclease-cleavage site).", "contents": "Electron microscope localization of a protein bound near the origin of simian virus 40 DNA replication. A salt-stable complex of protein and viral DNA obtained from Simian virus 40 (SV40)-infected monkey cells or mature SV40 virions has a novel structure. When viewed by high resolution electron microscopy, the circular SV40 DNA molecule has bound to it one to three globular protein \"knobs\". Using ecoRI and hpaII restriction endonucleases, each of which can cleave SV40 DNA once at a known location (10, 11, 12, 14), the bound protein can be localized at 0.7 plus or minis 0.05 on the SV40 DNA physical map (SV40 fractional length, clockwise from the ecoRI endonuclease-cleavage site)."} {"id": "PMID:163342", "title": "Characterization of human papovavirus BK DNA.", "content": "The DNA of the BK virus (BKV) human papovavirus was found to be heterogeneous, consisting of at least four discrete species of DNA. Only the largest of these four species, BKV DNA (i), which has a molecular weight calculated to be 96% that of simian virus 40 (SV40) DNA, was infectious. Homogeneous preparations of BKV DNA were obtained, however, from virions purified after low multiplicity infections of human embryonic kidney cells. BKV DNA (i) was shown to contain a single R-Eco RI and four R-Hind cleavage sites. The R-Eco RI site was localized in the largest R-Hind cleavage fragment. Radiolabeled BKV DNA reassociated slightly faster than SV40 DNA; 20 to 30% polynucleotide sequence homology was demonstrated between the genomes of BKV and SV40 when the reaction was monitored by chromatography on hydroxyapatite.", "contents": "Characterization of human papovavirus BK DNA. The DNA of the BK virus (BKV) human papovavirus was found to be heterogeneous, consisting of at least four discrete species of DNA. Only the largest of these four species, BKV DNA (i), which has a molecular weight calculated to be 96% that of simian virus 40 (SV40) DNA, was infectious. Homogeneous preparations of BKV DNA were obtained, however, from virions purified after low multiplicity infections of human embryonic kidney cells. BKV DNA (i) was shown to contain a single R-Eco RI and four R-Hind cleavage sites. The R-Eco RI site was localized in the largest R-Hind cleavage fragment. Radiolabeled BKV DNA reassociated slightly faster than SV40 DNA; 20 to 30% polynucleotide sequence homology was demonstrated between the genomes of BKV and SV40 when the reaction was monitored by chromatography on hydroxyapatite."} {"id": "PMID:163343", "title": "Studies of polyoma virus DNA: cleavage map of the polyoma virus genome.", "content": "A small-plaque polyoma virus, MPC-1, was isolated from a mouse plasmacytoma. The DNA of this polyoma virus was cleaved with a restriction enzyme from Haemophilus influenzae (Hin d), and the molecular weights of the limit products were analyzed by electrophoresis and electron microscopy. The fragments produced by this enzyme have been ordered by analysis of partial digest products. A physical map of the polyoma virus genome was then constructed.", "contents": "Studies of polyoma virus DNA: cleavage map of the polyoma virus genome. A small-plaque polyoma virus, MPC-1, was isolated from a mouse plasmacytoma. The DNA of this polyoma virus was cleaved with a restriction enzyme from Haemophilus influenzae (Hin d), and the molecular weights of the limit products were analyzed by electrophoresis and electron microscopy. The fragments produced by this enzyme have been ordered by analysis of partial digest products. A physical map of the polyoma virus genome was then constructed."} {"id": "PMID:163344", "title": "RNA synthesis in cells infected with herpes simplex virus. IX. Evidence for accumulation of abundant symmetric transcripts in nuclei.", "content": "RNA extracted from nuclei of 8-h infected cells drove approximately 50% of herpes virus DNA into DNA-RNA hybrid. The same RNA, preannealed under conditions which allowed base pairing to take place, drove only 35% of the DNA into DNA-RNA hybrid; further annealing of the RNA did not diminish the amount of RNA sequences remaining available for subsequent hybridization with DNA. Upon denaturation of the preannealed RNA, the RNA sequences sequestered during preannealing became available again for hybridization with DNA. The base pairing that occurred during preincubation of the RNA was inter-molecular, since it was RNA concentration dependent and was not affected by limited alkaline hydrolysis. The nuclear viral transcripts that remained available for hybridization, after preannealing of the RNA, were subset of the RNA sequences that accumulated in the cytoplasm of infected cells. In addition, a small amount (derived from 5% or less of the viral DNA) of complementary transcripts was detected in the cytoplasm.", "contents": "RNA synthesis in cells infected with herpes simplex virus. IX. Evidence for accumulation of abundant symmetric transcripts in nuclei. RNA extracted from nuclei of 8-h infected cells drove approximately 50% of herpes virus DNA into DNA-RNA hybrid. The same RNA, preannealed under conditions which allowed base pairing to take place, drove only 35% of the DNA into DNA-RNA hybrid; further annealing of the RNA did not diminish the amount of RNA sequences remaining available for subsequent hybridization with DNA. Upon denaturation of the preannealed RNA, the RNA sequences sequestered during preannealing became available again for hybridization with DNA. The base pairing that occurred during preincubation of the RNA was inter-molecular, since it was RNA concentration dependent and was not affected by limited alkaline hydrolysis. The nuclear viral transcripts that remained available for hybridization, after preannealing of the RNA, were subset of the RNA sequences that accumulated in the cytoplasm of infected cells. In addition, a small amount (derived from 5% or less of the viral DNA) of complementary transcripts was detected in the cytoplasm."} {"id": "PMID:163345", "title": "Screening procedure for complementation-dependent mutants of vesicular stomatitis virus.", "content": "To isolate new types of vesicular stomatitis virus (VSV) mutants, a four-stage screen was developed which identifies and characterizes mutants capable of complementing the defect in the VSV temperature-sensitive mutant tsG11. Two types of mutants of VSV, Indiana serotype, have been found by using the screen; they are new temperature-sensitive mutants which are, of necessity, not in complementation group I and mutants which do not produce plaques under conditions of single infection at 31 C (the normal permissive temperature) and are, therefore, called complementation-dependent mutants. The newly isolated, temperature-sensitive mutants fall into three complementation groups, two of which are congruent with known complementation groups; the newly identified group extends to six the number of complementation groups of VSV Indiana. The nature of the complementation-dependent mutants has not been established, but one was shown to not contain a significant deletion in its nucleic acid.", "contents": "Screening procedure for complementation-dependent mutants of vesicular stomatitis virus. To isolate new types of vesicular stomatitis virus (VSV) mutants, a four-stage screen was developed which identifies and characterizes mutants capable of complementing the defect in the VSV temperature-sensitive mutant tsG11. Two types of mutants of VSV, Indiana serotype, have been found by using the screen; they are new temperature-sensitive mutants which are, of necessity, not in complementation group I and mutants which do not produce plaques under conditions of single infection at 31 C (the normal permissive temperature) and are, therefore, called complementation-dependent mutants. The newly isolated, temperature-sensitive mutants fall into three complementation groups, two of which are congruent with known complementation groups; the newly identified group extends to six the number of complementation groups of VSV Indiana. The nature of the complementation-dependent mutants has not been established, but one was shown to not contain a significant deletion in its nucleic acid."} {"id": "PMID:163346", "title": "Temperature-sensitive virus derived from BHK cells persistently infected with HVJ (Sendai virus).", "content": "BHK-HVJ cells, a cell line of baby hamster kidney cells persistantly infected with HVJ (Sendai virus), started to produce infectious virus by shifting down the incubation temperature from 38 to 32 C. The virus derived from BHK-HVJ cells, designated as HJV-pB, was effectively neutralized with antibody against wild-type virus (HVJ-W) which was used for the establishment of BHK-HVJ cells. HVJ-pB replicated in eggs at 32 C, but not at 38 C, while HVJ-W grew equally well at both temperatures. When BHK cells infected with HVJ-PB were incubated at 38 C, production of infectious virus, hemagglutinin, and neuraminidase was markedly restrained, whereas a considerable amount of viral nucleocapisid and envelope antigens was detected in the cells by complement fixation tests. These viral activities became detectable immediately after temperature shift-down from 38 to 32 C even at the later stage of infection. HVJ-pB was indistinguishable from HJV-W with respect to particle size, density, and morphological characteristics, but appeared to possess a higher neuraminidase activity and was inactivated more rapidly at 50 C than HVJ-W. HVJ-pB was less cytocidal and could easily cause latent infection in BHK and mouse L cells.", "contents": "Temperature-sensitive virus derived from BHK cells persistently infected with HVJ (Sendai virus). BHK-HVJ cells, a cell line of baby hamster kidney cells persistantly infected with HVJ (Sendai virus), started to produce infectious virus by shifting down the incubation temperature from 38 to 32 C. The virus derived from BHK-HVJ cells, designated as HJV-pB, was effectively neutralized with antibody against wild-type virus (HVJ-W) which was used for the establishment of BHK-HVJ cells. HVJ-pB replicated in eggs at 32 C, but not at 38 C, while HVJ-W grew equally well at both temperatures. When BHK cells infected with HVJ-PB were incubated at 38 C, production of infectious virus, hemagglutinin, and neuraminidase was markedly restrained, whereas a considerable amount of viral nucleocapisid and envelope antigens was detected in the cells by complement fixation tests. These viral activities became detectable immediately after temperature shift-down from 38 to 32 C even at the later stage of infection. HVJ-pB was indistinguishable from HJV-W with respect to particle size, density, and morphological characteristics, but appeared to possess a higher neuraminidase activity and was inactivated more rapidly at 50 C than HVJ-W. HVJ-pB was less cytocidal and could easily cause latent infection in BHK and mouse L cells."} {"id": "PMID:163347", "title": "Cycloheximide induction of xenotropic type C virus from synchronized mouse cells: metabolic requirements for virus activation.", "content": "The information for type C RNA viruses is genetically transmitted within the cellular DNA of the normal mouse cell. These viruses can be induced after exposure of cells to two classes of chemicals, inhibitors of protein synthesis and halogenated pyrimidines. The metabolic requirements for activation of one endogenous virus of BALB/c mouse cells by representatives of each class of drugs were studies. Cycloheximide and iododeoxyuridine each induce virus efficiently from cultures in exponential growth but are inactive on cells in stationary phase. However, cells are maximally sensitive to the actions of each drug at different times within the cell cycle. Further, virus induction in response to each is differentially inhibited under conditions of simultaneous cell exposure to inhibitors of DNA or RNA synthesis. The results provide support for the concept that inhibitors of protein synthesis and halogenated pyrimidines act by different mechanisms to induce type C virus release.", "contents": "Cycloheximide induction of xenotropic type C virus from synchronized mouse cells: metabolic requirements for virus activation. The information for type C RNA viruses is genetically transmitted within the cellular DNA of the normal mouse cell. These viruses can be induced after exposure of cells to two classes of chemicals, inhibitors of protein synthesis and halogenated pyrimidines. The metabolic requirements for activation of one endogenous virus of BALB/c mouse cells by representatives of each class of drugs were studies. Cycloheximide and iododeoxyuridine each induce virus efficiently from cultures in exponential growth but are inactive on cells in stationary phase. However, cells are maximally sensitive to the actions of each drug at different times within the cell cycle. Further, virus induction in response to each is differentially inhibited under conditions of simultaneous cell exposure to inhibitors of DNA or RNA synthesis. The results provide support for the concept that inhibitors of protein synthesis and halogenated pyrimidines act by different mechanisms to induce type C virus release."} {"id": "PMID:163349", "title": "The 5' nucleotide sequence of vesicular stomatitis viral RNA.", "content": "The 5' nucleotide sequence of vesicular stomatitis viral RNA is pppApCpGp....", "contents": "The 5' nucleotide sequence of vesicular stomatitis viral RNA. The 5' nucleotide sequence of vesicular stomatitis viral RNA is pppApCpGp...."} {"id": "PMID:163348", "title": "Analysis of uridine incorporation in chicken embryo cells infected by vesicular stomatitis virus and its temperature-sensitive mutants: uridine transport.", "content": "The shut-off of RNA synthesis in chicken embryo cells, after infection with vesicular stomatitis virus, is partially due to a reduced capacity of the infected cells to transport uridine. Permeability to uridine decreases exponentially after infection. This loss of ability to transport uridine may be caused either by structural components of the input virions or may result from the expression of the viral gene products. In the latter case, only minor levels of viral transcription is sufficient to modify cellular permeability, since, even at low multiplicities, RNA minus temperature-sensitive (ts) mutants of vesicular stomatitis virus bring about a significant diminution of uridine incorporation in cells infected under nonpermissive conditions. Experiments with mutants of group III suggest that the M protein of the viral envelope may play a role in the sequence of events that modifies uridine transport. In addition to this cause of the diminution of incorporation of uridine by infected cells, another mechanism is noted which requires protein synthesis.", "contents": "Analysis of uridine incorporation in chicken embryo cells infected by vesicular stomatitis virus and its temperature-sensitive mutants: uridine transport. The shut-off of RNA synthesis in chicken embryo cells, after infection with vesicular stomatitis virus, is partially due to a reduced capacity of the infected cells to transport uridine. Permeability to uridine decreases exponentially after infection. This loss of ability to transport uridine may be caused either by structural components of the input virions or may result from the expression of the viral gene products. In the latter case, only minor levels of viral transcription is sufficient to modify cellular permeability, since, even at low multiplicities, RNA minus temperature-sensitive (ts) mutants of vesicular stomatitis virus bring about a significant diminution of uridine incorporation in cells infected under nonpermissive conditions. Experiments with mutants of group III suggest that the M protein of the viral envelope may play a role in the sequence of events that modifies uridine transport. In addition to this cause of the diminution of incorporation of uridine by infected cells, another mechanism is noted which requires protein synthesis."} {"id": "PMID:163350", "title": "In vitro polyoma DNA synthesis: requirement for cytoplasmic factors.", "content": "Purified nuclei from polyoma-infected mouse (3T3) cells were found to be greatly reduced in their ability to synthesize viral DNA in vitro when compared with a crude system consisting of an unfractionated hypotonic lysate of the infected cells. The synthetic capacity of the nuclei could be fully reconstituted when a high-speed cytoplasmic supernatant was added back to them. Cytosols from uninfected mouse, monkey, and hamster cells were equally as effective in stimulating purified nuclei as that of virus-infected mouse cells. Optimal complementation required high concentrations of the cytosol, and most of the complementing activity was destroyed by heating to 60 C. Dialysis had no effect on the activity. Analysis of the viral DNA synthesized in purified nuclei showed an accumulation of Okazaki-type short DNA chains, which could be chased into viral progeny DNA strands if cytosol was added back to the nuclei. Kinetic analysis of the pulse-labeling pattern of viral replicative DNA showed a strong dependence of the extension of viral progeny strands and of the processing of Okazaki-type fragments on the amount of cytosol present during the reaction. It is suggested that the cytoplasmic DNA polymerase might be one of the active components in the cytosol, but most likely not the only one.", "contents": "In vitro polyoma DNA synthesis: requirement for cytoplasmic factors. Purified nuclei from polyoma-infected mouse (3T3) cells were found to be greatly reduced in their ability to synthesize viral DNA in vitro when compared with a crude system consisting of an unfractionated hypotonic lysate of the infected cells. The synthetic capacity of the nuclei could be fully reconstituted when a high-speed cytoplasmic supernatant was added back to them. Cytosols from uninfected mouse, monkey, and hamster cells were equally as effective in stimulating purified nuclei as that of virus-infected mouse cells. Optimal complementation required high concentrations of the cytosol, and most of the complementing activity was destroyed by heating to 60 C. Dialysis had no effect on the activity. Analysis of the viral DNA synthesized in purified nuclei showed an accumulation of Okazaki-type short DNA chains, which could be chased into viral progeny DNA strands if cytosol was added back to the nuclei. Kinetic analysis of the pulse-labeling pattern of viral replicative DNA showed a strong dependence of the extension of viral progeny strands and of the processing of Okazaki-type fragments on the amount of cytosol present during the reaction. It is suggested that the cytoplasmic DNA polymerase might be one of the active components in the cytosol, but most likely not the only one."} {"id": "PMID:163351", "title": "Temporal appearance of bacteriophage T4-modified valyl tRNA synthetase in Escherichia coli.", "content": "Bacteriophage T4-induced modification of Escherichia coli vlayl-tRNA synthetase (EC 6.1.1.9) requires: synthesis of a phage-gene specified tau factor, addition of the factor to host valyl-tRNA synthetase to produce a urea-stable enzyme, and interaction of the modified enzyme with tRNA to produce a more rapidly sedimenting valyl-tRNA synthetase activity on sucrose density gradients. This report demonstrates that the coincident, chloramphenicol-sensitive appearance of urea-stable and rapidly sedimenting valyl-tRNA synthetase activity are immediate early phage functions. It implies that once the tau factor is synthesized, further interactions are stoichiometric rather than catalytic. The potential for valyl-tRNA synthetase modification accumylates when E. coli is infected with T4 PHAGE IN THE PRESENCE OF CHLORAMPHINICOL AND IS EXPRESSED DURING THE RESUMPTION OF PROTEIN SYNTHESIS WHEREAS FURTHER RNA synthesis is inhibited by rifampicin. The modification phenomenon occurs similarly in several strains of E. coli and represents a novel virus-host interaction.", "contents": "Temporal appearance of bacteriophage T4-modified valyl tRNA synthetase in Escherichia coli. Bacteriophage T4-induced modification of Escherichia coli vlayl-tRNA synthetase (EC 6.1.1.9) requires: synthesis of a phage-gene specified tau factor, addition of the factor to host valyl-tRNA synthetase to produce a urea-stable enzyme, and interaction of the modified enzyme with tRNA to produce a more rapidly sedimenting valyl-tRNA synthetase activity on sucrose density gradients. This report demonstrates that the coincident, chloramphenicol-sensitive appearance of urea-stable and rapidly sedimenting valyl-tRNA synthetase activity are immediate early phage functions. It implies that once the tau factor is synthesized, further interactions are stoichiometric rather than catalytic. The potential for valyl-tRNA synthetase modification accumylates when E. coli is infected with T4 PHAGE IN THE PRESENCE OF CHLORAMPHINICOL AND IS EXPRESSED DURING THE RESUMPTION OF PROTEIN SYNTHESIS WHEREAS FURTHER RNA synthesis is inhibited by rifampicin. The modification phenomenon occurs similarly in several strains of E. coli and represents a novel virus-host interaction."} {"id": "PMID:163352", "title": "Alteration of capsid proteins of coxsackievirus A13 by low ionic concentrations.", "content": "Several group A coxsackieviruses (A13, 15, 18, and 21), but not polioviruses or group B coxsackieviruses, are rapidly inactivated in low ionic strength solutions at neutral pH. The extent of inactivation is dependent upon temperature and molarity. Virions inactivated in this manner contain a normal complement of infectious RNA which remains in a state resistant to the action of ribonuclease. However, more than 95% of the virus particles are unable to attach to susceptible cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that coxsackievirus A13 virions contain five structural polypeptides (VP1, VP2a, VP2b, VP3, and VP4). Electrophoretic analysis indicates that inactivation of coxsackievirus A13 in low ionic strength solutions is due to the specific loss of the smallest polypeptide VP4 from the virus particle. These results suggest that adsorption of coxsackievirus A13 to receptors on susceptible cells is dependent upon the presence of the capsid protein VP4.", "contents": "Alteration of capsid proteins of coxsackievirus A13 by low ionic concentrations. Several group A coxsackieviruses (A13, 15, 18, and 21), but not polioviruses or group B coxsackieviruses, are rapidly inactivated in low ionic strength solutions at neutral pH. The extent of inactivation is dependent upon temperature and molarity. Virions inactivated in this manner contain a normal complement of infectious RNA which remains in a state resistant to the action of ribonuclease. However, more than 95% of the virus particles are unable to attach to susceptible cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that coxsackievirus A13 virions contain five structural polypeptides (VP1, VP2a, VP2b, VP3, and VP4). Electrophoretic analysis indicates that inactivation of coxsackievirus A13 in low ionic strength solutions is due to the specific loss of the smallest polypeptide VP4 from the virus particle. These results suggest that adsorption of coxsackievirus A13 to receptors on susceptible cells is dependent upon the presence of the capsid protein VP4."} {"id": "PMID:163353", "title": "Stimulation of adenovirus replication in simian cells in the absence of a helper virus by pretreatment of the cells with iododeoxyuridine.", "content": "Pretreatment of African green monkey kidney cells with 50 mu g of 5'-iododeoxyruidine (IUdR) per ml can modify their susceptibility to the replication of human adenovirus type 7 in the absence of simian virus 40 (SV40) although this enhancement of adenovirus replication is not as efficient as that of the helper SV40 virus. Since the number of infectious centers remains unchanged after IUdR pretreatment whereas the burst size of virus from each infected cell increases, the IUdR appears to allow each infected cell to produce more virus. Cell DNA synthesis appears to be stimulated in IUdR pretreated cells infected with adenovirus 7, but the host cell DNA synthesized is small enough to remain in the Hirt supernatant fluid. The modification of susceptibility to adenovirus replication and the changed pattern of cell DNA synthesis is stable for at least two additional cell passages of the pretreated cells.", "contents": "Stimulation of adenovirus replication in simian cells in the absence of a helper virus by pretreatment of the cells with iododeoxyuridine. Pretreatment of African green monkey kidney cells with 50 mu g of 5'-iododeoxyruidine (IUdR) per ml can modify their susceptibility to the replication of human adenovirus type 7 in the absence of simian virus 40 (SV40) although this enhancement of adenovirus replication is not as efficient as that of the helper SV40 virus. Since the number of infectious centers remains unchanged after IUdR pretreatment whereas the burst size of virus from each infected cell increases, the IUdR appears to allow each infected cell to produce more virus. Cell DNA synthesis appears to be stimulated in IUdR pretreated cells infected with adenovirus 7, but the host cell DNA synthesized is small enough to remain in the Hirt supernatant fluid. The modification of susceptibility to adenovirus replication and the changed pattern of cell DNA synthesis is stable for at least two additional cell passages of the pretreated cells."} {"id": "PMID:163354", "title": "Replication of polyoma DNA in isolated nuclei. V. Complementation of in vitro DNA replication.", "content": "Nuclei from polyoma-infected 3T6 fibroblasts elongate in vitro the progeny strands of the replicative intermediates of polyoma DNA. When high concentrations of such nuclei were incubated, short DNA fragments were formed and subsequently added onto growing progeny strands. When nuclei were repeatedly washed with buffer containing detergent and then incubated at low concentrations. DNA synthesis was decreased. In particular, the joining process was reduced, resulting in an accumulation of short DNA fragments. All aspects of the synthetic capacity of the nuclei were restored by addition of cytoplasmic extract. Additions of purified enzymes (polynucleotide ligase from calf thymus or Escherichia coli together with E. coli DNA polymerase I) increased the joining function of the nuclei. The system can be used for the identification of the enzymatic steps concerned with polyoma DNA replication.", "contents": "Replication of polyoma DNA in isolated nuclei. V. Complementation of in vitro DNA replication. Nuclei from polyoma-infected 3T6 fibroblasts elongate in vitro the progeny strands of the replicative intermediates of polyoma DNA. When high concentrations of such nuclei were incubated, short DNA fragments were formed and subsequently added onto growing progeny strands. When nuclei were repeatedly washed with buffer containing detergent and then incubated at low concentrations. DNA synthesis was decreased. In particular, the joining process was reduced, resulting in an accumulation of short DNA fragments. All aspects of the synthetic capacity of the nuclei were restored by addition of cytoplasmic extract. Additions of purified enzymes (polynucleotide ligase from calf thymus or Escherichia coli together with E. coli DNA polymerase I) increased the joining function of the nuclei. The system can be used for the identification of the enzymatic steps concerned with polyoma DNA replication."} {"id": "PMID:163355", "title": "Early events after infection of Escherichia coli by bacteriophage T5. Induction of a 5'-nucleotidase activity and excretion of free bases.", "content": "Thymine-containing compounds, produced degradation of Escherichia coli DNA after infection of the cells with bacteriophage T5, did not accumulate in the cell but were excreted into the medium as the DNA was degraded. The ultimate degradation product was extracellular thymine that was not reutilized when T5 DNA synthesis began. This excretion of thymine may have been due in part to the induction of 5'-nucleotidase activity within 3 min after T5 infection. The level of this activity reached a maximum between 4 to 6 min after infection and then rapidly declined to its preinfection level by 10 to 15 min after infection. Chloramphenicol added before or soon after infection prevented the appearance of the nucleotidase. The induced nucleotidase activity was active not only on dTMP but also on dAMP, dGMP, and dCMP.", "contents": "Early events after infection of Escherichia coli by bacteriophage T5. Induction of a 5'-nucleotidase activity and excretion of free bases. Thymine-containing compounds, produced degradation of Escherichia coli DNA after infection of the cells with bacteriophage T5, did not accumulate in the cell but were excreted into the medium as the DNA was degraded. The ultimate degradation product was extracellular thymine that was not reutilized when T5 DNA synthesis began. This excretion of thymine may have been due in part to the induction of 5'-nucleotidase activity within 3 min after T5 infection. The level of this activity reached a maximum between 4 to 6 min after infection and then rapidly declined to its preinfection level by 10 to 15 min after infection. Chloramphenicol added before or soon after infection prevented the appearance of the nucleotidase. The induced nucleotidase activity was active not only on dTMP but also on dAMP, dGMP, and dCMP."} {"id": "PMID:163356", "title": "Physiological characterization of temperature-sensitive mutants of mengovirus.", "content": "Twenty-four temperature-sensitive mutants of mengovirus were characterized physiologically with respect to phenotype. The mutants were separated into four classes on the basis of viral RNA synthesis. L-67-S cells infected with five of the mutants synthesized little viral RNA at 39.5 C. These mutants are designated RNA-. One mutant is designated RNA* since its RNA synthesis is altered at both 39.5 and 31.5 C. The other mutants were divided into two groups, RNA plus or minus (25 TO 49% of wild-type RNA synthesis) and RNA plus (50 to 100% of wild-type RNA synthesis). The time of expression of the mutation in the RNA- mutants was estimated from the results of reciprocal temperature-shift experiments. The mutatation in ts12 appears to be expressed at the time RNA synthesis normally begins. The defect in three of the mutants was expressed 1 to 2 h before RNA synthesis is normally detectable. Protein synthesis is required before RNA synthesis begins when the cells are shifted from 39.5 to 31.5 C. The RNA polymerase synthesized by cells infected with these RNA- mutants at 31.5 C was stable and fully active when assayed at 39.5 C in vitro. The sedimentation profiles of the viral RNA synthesized by cells infected with RNA plus and RNA plus or minus mutants are similar to wild-type profiles with the exception of ts148. Cells infected with this RNA plus or minus mutant synthesize RNA that sediments in a sucrose gradient like replicative-intermediate RNA, but little mature viral RNA is evident. The results of step-up experiments indicate that the temperature-sensitive period for the majority of the RNA plus and RNA plus and minus mutants extends through most of the replicative cycle. The temperature-sensitive defect of four of the mutants, however, was expressed in the first hour, suggesting that some undefined early function is required for the eventual maturation of mengovirus. The virions of three of the RNA- mutants were more thermolabile than wild-type virions. Five of the RNA plus and RNA plus or minus mutants were also thermolabile. Genetic complementation at a significant level was not detectable in mixed infections of the mutants described.", "contents": "Physiological characterization of temperature-sensitive mutants of mengovirus. Twenty-four temperature-sensitive mutants of mengovirus were characterized physiologically with respect to phenotype. The mutants were separated into four classes on the basis of viral RNA synthesis. L-67-S cells infected with five of the mutants synthesized little viral RNA at 39.5 C. These mutants are designated RNA-. One mutant is designated RNA* since its RNA synthesis is altered at both 39.5 and 31.5 C. The other mutants were divided into two groups, RNA plus or minus (25 TO 49% of wild-type RNA synthesis) and RNA plus (50 to 100% of wild-type RNA synthesis). The time of expression of the mutation in the RNA- mutants was estimated from the results of reciprocal temperature-shift experiments. The mutatation in ts12 appears to be expressed at the time RNA synthesis normally begins. The defect in three of the mutants was expressed 1 to 2 h before RNA synthesis is normally detectable. Protein synthesis is required before RNA synthesis begins when the cells are shifted from 39.5 to 31.5 C. The RNA polymerase synthesized by cells infected with these RNA- mutants at 31.5 C was stable and fully active when assayed at 39.5 C in vitro. The sedimentation profiles of the viral RNA synthesized by cells infected with RNA plus and RNA plus or minus mutants are similar to wild-type profiles with the exception of ts148. Cells infected with this RNA plus or minus mutant synthesize RNA that sediments in a sucrose gradient like replicative-intermediate RNA, but little mature viral RNA is evident. The results of step-up experiments indicate that the temperature-sensitive period for the majority of the RNA plus and RNA plus and minus mutants extends through most of the replicative cycle. The temperature-sensitive defect of four of the mutants, however, was expressed in the first hour, suggesting that some undefined early function is required for the eventual maturation of mengovirus. The virions of three of the RNA- mutants were more thermolabile than wild-type virions. Five of the RNA plus and RNA plus or minus mutants were also thermolabile. Genetic complementation at a significant level was not detectable in mixed infections of the mutants described."} {"id": "PMID:163357", "title": "Human cytomegalovirus stimulates host cell RNA synthesis.", "content": "Human cytomegalovirus infection of human fibroblast cells (WI-38) induced cellular RNA synthesis. The RNA synthesis in infected cultures preceded the synthesis of viral DNA and progeny virus by approximately 24 h. RNA species synthesized in infected cells included ribosomal 28S and 18S; and 4S transfer RNA; all were markedly increased in comparison to uninfected cells. This induction of host cell RNA synthesis was dependent upon a protein(s) that was synthesized during the early stages of infection.", "contents": "Human cytomegalovirus stimulates host cell RNA synthesis. Human cytomegalovirus infection of human fibroblast cells (WI-38) induced cellular RNA synthesis. The RNA synthesis in infected cultures preceded the synthesis of viral DNA and progeny virus by approximately 24 h. RNA species synthesized in infected cells included ribosomal 28S and 18S; and 4S transfer RNA; all were markedly increased in comparison to uninfected cells. This induction of host cell RNA synthesis was dependent upon a protein(s) that was synthesized during the early stages of infection."} {"id": "PMID:163358", "title": "In vitro synthesis of DNA in nuclei isolated from human lung cells infected with herpes simplex type II virus.", "content": "An isolated nuclei system prepared from herpes type II- and mock-infected human embryonic lung cells is able to synthesize cellular and viral DNA in the same proportion as in vivo at various times after infection. Incorporation of (3H)TTP in the in vitro reaction mixture requires Mg2 plus and ATP. Overall in vitro DNA synthesis in nuclei isolated from herpes-infected cells is semiconservative as demonstrated by bromodeoxyuridine-substituted DNA density-transfer experiments, but exhibits a significant fraction of repair-type replication. Relative rates of total DNA synthesis in vitro and in vivo are the same any time after infection. Isolated nuclei synthesize cell and viral DNA for a length of time and at a rate dependent upon the incubation temperature, but there are differences in the length of time of linear in vitro DNA synthesis between herpes- and mock-infected cells. The temperature optima for in vitro DNA synthesis differ significantly for herpes- and mock-infected cells, and are the same for cells abortively infected with herpes type II as for mock-infected cells.", "contents": "In vitro synthesis of DNA in nuclei isolated from human lung cells infected with herpes simplex type II virus. An isolated nuclei system prepared from herpes type II- and mock-infected human embryonic lung cells is able to synthesize cellular and viral DNA in the same proportion as in vivo at various times after infection. Incorporation of (3H)TTP in the in vitro reaction mixture requires Mg2 plus and ATP. Overall in vitro DNA synthesis in nuclei isolated from herpes-infected cells is semiconservative as demonstrated by bromodeoxyuridine-substituted DNA density-transfer experiments, but exhibits a significant fraction of repair-type replication. Relative rates of total DNA synthesis in vitro and in vivo are the same any time after infection. Isolated nuclei synthesize cell and viral DNA for a length of time and at a rate dependent upon the incubation temperature, but there are differences in the length of time of linear in vitro DNA synthesis between herpes- and mock-infected cells. The temperature optima for in vitro DNA synthesis differ significantly for herpes- and mock-infected cells, and are the same for cells abortively infected with herpes type II as for mock-infected cells."} {"id": "PMID:163359", "title": "Genetic transmission of endogenous N- and B-tropic murine leukemia viruses in low-leukemic strain C57BL/6.", "content": "Spontaneous expression of endogenous N- and B-tropic murine leukemia viruses was stu1bb), DDD (Fuv-1nn), DDD-Fvr (fv-1nn), (DDD or DDD-Fvr times C57BL/6)F1, and 16 partially inbredlines with either the Fv-1nn or Fv-1bb genotype, which had been established from hybrids between C57BL/6 and DDD-Fvr. When tested at middle age, virus-positive mice were found in C57BL/6, F1 hybrids, and 9 out of 16 partially inbred lines. N-tropic viruses were isolated from Fv-1nn, Fv-1bb mice, whereas B-tropic viruses, except for one isolate, were from Fv-1bb mice only. C57BL/6 mice were positive for both N- and B-tropic viruses, whereas DDD-Fvr mice were negative. With respect to the Fv-1 genotype and the presence of endogenous murine leukemia viruses, the partially inbred lines were grouped into five types: (i) Fv-1bb, both N- and B-tropic virus positive, like C57BL/6; (ii) Fv-1nn, virus negative, like DDD-Fvr; (iii) Fv-1bb, virus negative; (iv) Fv-1nn, only N-tropic virus positive; and (v) less convincingly, Fv-1bb, only B-tropic virus positive. These findings indicate that the transmission of N- and B-tropic viruses in C57BL/6 is genetically controlled and that the expression of B-tropic virus, but not of N-tropic virus, is closely associated with the Fv-1 genotype.", "contents": "Genetic transmission of endogenous N- and B-tropic murine leukemia viruses in low-leukemic strain C57BL/6. Spontaneous expression of endogenous N- and B-tropic murine leukemia viruses was stu1bb), DDD (Fuv-1nn), DDD-Fvr (fv-1nn), (DDD or DDD-Fvr times C57BL/6)F1, and 16 partially inbredlines with either the Fv-1nn or Fv-1bb genotype, which had been established from hybrids between C57BL/6 and DDD-Fvr. When tested at middle age, virus-positive mice were found in C57BL/6, F1 hybrids, and 9 out of 16 partially inbred lines. N-tropic viruses were isolated from Fv-1nn, Fv-1bb mice, whereas B-tropic viruses, except for one isolate, were from Fv-1bb mice only. C57BL/6 mice were positive for both N- and B-tropic viruses, whereas DDD-Fvr mice were negative. With respect to the Fv-1 genotype and the presence of endogenous murine leukemia viruses, the partially inbred lines were grouped into five types: (i) Fv-1bb, both N- and B-tropic virus positive, like C57BL/6; (ii) Fv-1nn, virus negative, like DDD-Fvr; (iii) Fv-1bb, virus negative; (iv) Fv-1nn, only N-tropic virus positive; and (v) less convincingly, Fv-1bb, only B-tropic virus positive. These findings indicate that the transmission of N- and B-tropic viruses in C57BL/6 is genetically controlled and that the expression of B-tropic virus, but not of N-tropic virus, is closely associated with the Fv-1 genotype."} {"id": "PMID:163360", "title": "Scanning electron microscopic studies of virus-infected cells. I. Cytopathic effects and maturation of vesicular stomatitis virus in L2 cells.", "content": "L2 cells infected with vesicular stomatitis virus under single-cycle conditions have been studied by scanning electron microscopy after preparation by the critical point drying technique. Three dimensional images of intact cells show bullet-shaped vesicular stomatitis virus virions budding singly and in radiating clusters both from the plasma membrane between cellular microvilli and from the sides of microvilli. Virus-induced cytopathic effects observed by scanning electron microscopy include intermeshing of microvilli, loss of filipodia which attach cells to the substrate, and rounding up and detachment of infected cells from the substrate.", "contents": "Scanning electron microscopic studies of virus-infected cells. I. Cytopathic effects and maturation of vesicular stomatitis virus in L2 cells. L2 cells infected with vesicular stomatitis virus under single-cycle conditions have been studied by scanning electron microscopy after preparation by the critical point drying technique. Three dimensional images of intact cells show bullet-shaped vesicular stomatitis virus virions budding singly and in radiating clusters both from the plasma membrane between cellular microvilli and from the sides of microvilli. Virus-induced cytopathic effects observed by scanning electron microscopy include intermeshing of microvilli, loss of filipodia which attach cells to the substrate, and rounding up and detachment of infected cells from the substrate."} {"id": "PMID:163361", "title": "Inhibition of bacteriophage PBS2 replication in Bacillus subtilis by phleomycin.", "content": "Phleomycin is an effective inhibitor of the replication of Bacillus subtilis bacteriophage PBS2, whose DNA contains uracil instead of thymine. Phleomycin does not affect the induction of the known phage enzymes involved in deoxyribonucleotide metabolism. But phage DNA synthesis is severely inhibited by phleomycin, and late virion protein synthesis is eliminated. These effects appear to result from a phleomycin-induced degradation of the parental phage DNA. Similar inhibitory and degradative effects on DNA are seen in phleomyinc-treated, uninfected cells. This system is unaffected by the related antibiotic, bleomycin.", "contents": "Inhibition of bacteriophage PBS2 replication in Bacillus subtilis by phleomycin. Phleomycin is an effective inhibitor of the replication of Bacillus subtilis bacteriophage PBS2, whose DNA contains uracil instead of thymine. Phleomycin does not affect the induction of the known phage enzymes involved in deoxyribonucleotide metabolism. But phage DNA synthesis is severely inhibited by phleomycin, and late virion protein synthesis is eliminated. These effects appear to result from a phleomycin-induced degradation of the parental phage DNA. Similar inhibitory and degradative effects on DNA are seen in phleomyinc-treated, uninfected cells. This system is unaffected by the related antibiotic, bleomycin."} {"id": "PMID:163362", "title": "Structural proteins of simian virus 40. I. Histone characteristics of low-molecular-weight polypeptides.", "content": "The DNA-associated polypeptides of simian virus 40 (SV40), VP4 (mol wt 14,000), VP5 (mol wt 12,000), and VP6 (mol wt 11,000), have several properties characteristic of cell histones. After extraction from purified SV40 with dilute acids, these three polypeptides co-electrophoresed on low pH polyacrylamide gels with monkey-kidney cell histones F3, F2b, and F2a1. No virus polypeptide co-electrophoresed with histone F1. Polypeptides VP4, 5, and 6 lacked tryptophan, and only VP4 contained cysteine, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis of virus labeled in vivo with (3H)lysine and either (14C)tryptophan or (35S)cystine. All of the capsid polypeptides VP1, 2, and 3 contained tryptophan whereas only VP1 and 2 contained cysteine. In addition, VP4, 5, and 6 are rich in arginine and lysine when compared with virus labeled with a mixture of amino acids. Analysis of virus grown in cells labeled prior to infection showed that VP4, 5 and 6 were labeled fivefold greater than the major capsid polypeptide, VP1, which indicates that they were partially derived from preexisting cell histones. Based on these data and on previously determined molecular weight estimates, we conclude that VP4, 5, and 6 are histones F3, F2b, and F2a1, respectively, although the possibility that SV40 contains a small amount of F2a2 could not be excluded.", "contents": "Structural proteins of simian virus 40. I. Histone characteristics of low-molecular-weight polypeptides. The DNA-associated polypeptides of simian virus 40 (SV40), VP4 (mol wt 14,000), VP5 (mol wt 12,000), and VP6 (mol wt 11,000), have several properties characteristic of cell histones. After extraction from purified SV40 with dilute acids, these three polypeptides co-electrophoresed on low pH polyacrylamide gels with monkey-kidney cell histones F3, F2b, and F2a1. No virus polypeptide co-electrophoresed with histone F1. Polypeptides VP4, 5, and 6 lacked tryptophan, and only VP4 contained cysteine, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis of virus labeled in vivo with (3H)lysine and either (14C)tryptophan or (35S)cystine. All of the capsid polypeptides VP1, 2, and 3 contained tryptophan whereas only VP1 and 2 contained cysteine. In addition, VP4, 5, and 6 are rich in arginine and lysine when compared with virus labeled with a mixture of amino acids. Analysis of virus grown in cells labeled prior to infection showed that VP4, 5 and 6 were labeled fivefold greater than the major capsid polypeptide, VP1, which indicates that they were partially derived from preexisting cell histones. Based on these data and on previously determined molecular weight estimates, we conclude that VP4, 5, and 6 are histones F3, F2b, and F2a1, respectively, although the possibility that SV40 contains a small amount of F2a2 could not be excluded."} {"id": "PMID:163363", "title": "Polyoma virus T antigen. I. Synthesis of modified heat-labile T angiten in cells transformed with the ts-a mutant.", "content": "In mouse cells transformed with the ts-a mutant of polyoma virus (ts-a-3T3), only low amounts of the virus-specific T antigen were synthesized at high temperature (39 C). After a shift-down to the permissive temperature (31 C), these cells exhibited the same level of T-antigen production as wild-type polyoma transformants. The T antigen produced by ts-a-transformed cells was inactivated at 39 C in vitro at a faster rate than that produced by wild-type-transformed cells. These observations indicate that T antigen is, or includes, a virus-coded peptide.", "contents": "Polyoma virus T antigen. I. Synthesis of modified heat-labile T angiten in cells transformed with the ts-a mutant. In mouse cells transformed with the ts-a mutant of polyoma virus (ts-a-3T3), only low amounts of the virus-specific T antigen were synthesized at high temperature (39 C). After a shift-down to the permissive temperature (31 C), these cells exhibited the same level of T-antigen production as wild-type polyoma transformants. The T antigen produced by ts-a-transformed cells was inactivated at 39 C in vitro at a faster rate than that produced by wild-type-transformed cells. These observations indicate that T antigen is, or includes, a virus-coded peptide."} {"id": "PMID:163364", "title": "Malignant transformation of hamster kidney cells by BK virus.", "content": "Primary hamster kidney cells were transformed by BK virus, a new human papovavirus. Transformed (HKBK) cell produced BK virus T antigen and induced tumors in hamsters that developed antibodies to BK virus T antigen. BK virus was rescued from HKBK cells by Sendai virus-assisted fusion with permissive cells. One out of six cell lines derived from HKBK cell-induced tumors showed the same characteristics as HKBK cells.", "contents": "Malignant transformation of hamster kidney cells by BK virus. Primary hamster kidney cells were transformed by BK virus, a new human papovavirus. Transformed (HKBK) cell produced BK virus T antigen and induced tumors in hamsters that developed antibodies to BK virus T antigen. BK virus was rescued from HKBK cells by Sendai virus-assisted fusion with permissive cells. One out of six cell lines derived from HKBK cell-induced tumors showed the same characteristics as HKBK cells."} {"id": "PMID:163365", "title": "Action of interferon in enucleated cells.", "content": "Interferon induces protection of enucleated BSC-1 cells against infectious vesicular stomatitis virus production if cells are treated before, but not after, enucleation.", "contents": "Action of interferon in enucleated cells. Interferon induces protection of enucleated BSC-1 cells against infectious vesicular stomatitis virus production if cells are treated before, but not after, enucleation."} {"id": "PMID:163366", "title": "Posttranscriptional selection of simian virus 40-specific RNA.", "content": "Analysis of the viral-specific RNA in simian virus 40(SV40)-infected monkey kidney cells indicated the extensive transcription of both DNA strands. These symmetrically transcribed sequences were localized in the nucleus of infected cells, whereas only the \"true\" early and late SV40 transcripts were found in the cytoplasm. These results suggest that selective posttranscriptional degradation and/or transport occurs after transcription of the viral DNA. On the basis of hybridization experiments with cytoplasmic RNA and the separated strands of the SV40 Hin fragments, the early SV40 region appears to include all of Hin fragments A, H, I, and B (48% of the genome), whereas the late region is represented in Hin fragments C, D, E, K, F, J, and G (52% of the genome).", "contents": "Posttranscriptional selection of simian virus 40-specific RNA. Analysis of the viral-specific RNA in simian virus 40(SV40)-infected monkey kidney cells indicated the extensive transcription of both DNA strands. These symmetrically transcribed sequences were localized in the nucleus of infected cells, whereas only the \"true\" early and late SV40 transcripts were found in the cytoplasm. These results suggest that selective posttranscriptional degradation and/or transport occurs after transcription of the viral DNA. On the basis of hybridization experiments with cytoplasmic RNA and the separated strands of the SV40 Hin fragments, the early SV40 region appears to include all of Hin fragments A, H, I, and B (48% of the genome), whereas the late region is represented in Hin fragments C, D, E, K, F, J, and G (52% of the genome)."} {"id": "PMID:163367", "title": "Proteins in intracellular simian virus 40 nucleoportein complexes: comparison with simian virus 40 core proteins.", "content": "Intracellular nucleoprotein complexes containing SV40 supercoiled DNA were purified from cell lysates by chromatography on hydroxyapatite columns followed by velocity sedimentation through sucrose gradients. The major protein components from purified complexes were identified as histone-like proteins. When analyzed by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels, complex proteins comigrated with viral core polypeptides VP4, VP5, VP6, and VP7. (3H) tryptophan was not detected in polypeptides from intracellular complexes or in the histone components from purified SV40 virus. However, a large amount of (3H) tryptophan was found in the viral polypeptide VP3 relative to that incorporated into the capsid polypeptides VP1 and VP2. Intracellular complexes contain 30 to 40% more protein than viral cores prepared by alkali dissociation of intact virus, but when complexes were exposed to the same alkaline conditions, protein also was removed from complexes and they subsequently co-sedimented with and had the same buoyant density as viral cores. The composition and physical similarities of nucleoprotein complex and viral cores indicate that complexes may have a role in the assembly of virions.", "contents": "Proteins in intracellular simian virus 40 nucleoportein complexes: comparison with simian virus 40 core proteins. Intracellular nucleoprotein complexes containing SV40 supercoiled DNA were purified from cell lysates by chromatography on hydroxyapatite columns followed by velocity sedimentation through sucrose gradients. The major protein components from purified complexes were identified as histone-like proteins. When analyzed by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels, complex proteins comigrated with viral core polypeptides VP4, VP5, VP6, and VP7. (3H) tryptophan was not detected in polypeptides from intracellular complexes or in the histone components from purified SV40 virus. However, a large amount of (3H) tryptophan was found in the viral polypeptide VP3 relative to that incorporated into the capsid polypeptides VP1 and VP2. Intracellular complexes contain 30 to 40% more protein than viral cores prepared by alkali dissociation of intact virus, but when complexes were exposed to the same alkaline conditions, protein also was removed from complexes and they subsequently co-sedimented with and had the same buoyant density as viral cores. The composition and physical similarities of nucleoprotein complex and viral cores indicate that complexes may have a role in the assembly of virions."} {"id": "PMID:163369", "title": "Quantitative assay for transformation of 3T3 cells by herpes simplex virus type 2.", "content": "The interaction of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) with Swiss/3T3 cells was investigated. Virus-induced cytopathic effects developed in the absence of production of infectious virus. HSV-2 inactivated with UV light (2, 4, 6, and 8 min) also induced cell death in the absence of virus replication. Cell death was not detectable after infection by HSV-2 that had been inactivated by UV irradiation for 10, 12, and 14 min. 3T3 cells infected with UV-inactivated virus (10 and 12 min) continued to replicate past the contact-inhibited monolayer normally associated with these cells. Infection of 3T3 cells with UV-irradiated USV-2 also induced the development of transformed foci. Transformed cells with an epithelioid of fibroblastoid morphology were identified and isolated. All HSV-2-transformed cell lines contained HSV-2-specific antigens detectable by immunofluorescence techniques. The maximum frequency of HSV-2-induced transformation was 3 times 105 PFU per transformed focus, and the observed transformation could be inhibited by pretreatment of the virus with specific antiserum. No type C particles were detected within five cell culture passages after transformation by HSV-2. Type C virus particles were detected after 10 cell culture passages of the HSV-2-transformed cell lines.", "contents": "Quantitative assay for transformation of 3T3 cells by herpes simplex virus type 2. The interaction of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) with Swiss/3T3 cells was investigated. Virus-induced cytopathic effects developed in the absence of production of infectious virus. HSV-2 inactivated with UV light (2, 4, 6, and 8 min) also induced cell death in the absence of virus replication. Cell death was not detectable after infection by HSV-2 that had been inactivated by UV irradiation for 10, 12, and 14 min. 3T3 cells infected with UV-inactivated virus (10 and 12 min) continued to replicate past the contact-inhibited monolayer normally associated with these cells. Infection of 3T3 cells with UV-irradiated USV-2 also induced the development of transformed foci. Transformed cells with an epithelioid of fibroblastoid morphology were identified and isolated. All HSV-2-transformed cell lines contained HSV-2-specific antigens detectable by immunofluorescence techniques. The maximum frequency of HSV-2-induced transformation was 3 times 105 PFU per transformed focus, and the observed transformation could be inhibited by pretreatment of the virus with specific antiserum. No type C particles were detected within five cell culture passages after transformation by HSV-2. Type C virus particles were detected after 10 cell culture passages of the HSV-2-transformed cell lines."} {"id": "PMID:163368", "title": "Stimulation of non-histone chromosomal protein synthesis in simian virus 40-infected simian cells.", "content": "The pattern of synthesis of non-histone chromosomal proteins in simian virus (SV) 40-infected African green monkey kidney cells was analyzed by polyacryl-amide gel electrophoresis to see whether the changes in chromosomal protein metabolism are involved in the viral-induced synthesis of cellular DNA and mRNA. During the prereplicative phase of infection, the rate of histone synthesis was decreased until 15 h postinfection, whereas that of non-histone protein synthesis was increased after 5 h postinfection and reached a maximum at 10 to 15 h postinfection when viral-induced synthesis of cellular DNA and mRNA began to be observed. Stimulation of non-histone protein synthesis was also observed in the infected cells treated with cytosine arabinoside and was dependent on the multiplicity of infection. Stimulation occurred in almost all species of non-histone proteins. These results suggest that the stimulation of non-histone protein synthesis is caused by an early SV40 function and occurs prior to the viral-induced synthesis of cellular DNA and mRNA. During the replicative phase of infection, a marked increase in the rate of synthesis was observed in the non-histone proteins with molecular weights of about 48,000, 35,000, and 23,000, which were subsequently found to be SV40 capsid proteins.", "contents": "Stimulation of non-histone chromosomal protein synthesis in simian virus 40-infected simian cells. The pattern of synthesis of non-histone chromosomal proteins in simian virus (SV) 40-infected African green monkey kidney cells was analyzed by polyacryl-amide gel electrophoresis to see whether the changes in chromosomal protein metabolism are involved in the viral-induced synthesis of cellular DNA and mRNA. During the prereplicative phase of infection, the rate of histone synthesis was decreased until 15 h postinfection, whereas that of non-histone protein synthesis was increased after 5 h postinfection and reached a maximum at 10 to 15 h postinfection when viral-induced synthesis of cellular DNA and mRNA began to be observed. Stimulation of non-histone protein synthesis was also observed in the infected cells treated with cytosine arabinoside and was dependent on the multiplicity of infection. Stimulation occurred in almost all species of non-histone proteins. These results suggest that the stimulation of non-histone protein synthesis is caused by an early SV40 function and occurs prior to the viral-induced synthesis of cellular DNA and mRNA. During the replicative phase of infection, a marked increase in the rate of synthesis was observed in the non-histone proteins with molecular weights of about 48,000, 35,000, and 23,000, which were subsequently found to be SV40 capsid proteins."} {"id": "PMID:163370", "title": "Induction of human cell DNA synthesis by herpes simplex virus type 2.", "content": "The effect of herpes simplex virus type 2 (HSV-2) infection on the synthesis of DNA in human embryonic fibroblast cells was determined at temperatures permissive (37 C) and nonpermissive (42 C) for virus multiplication. During incubation of HSV-2 infected cultures at 42 C for 2 to 4 days or after shift-down from 42 to 37 C, incorporation of (3H)TdR into total DNA was increased 2-to 30-fold as compared with mock-infected cultures. Analysis of the (3H)DNA suggested that host cell DNA synthesis was induced by HSV-2 infection. Induction of host cell DNA synthesis by HSV-2 also occurred in cells arrested in DNA replication by low serum concentration. The three strains of HSV-2 tested were capable of stimulating cellular DNA synthesis. Virus inactivated by UV irradiation, heat, or neutral red dye and light did not induce cellular DNA synthesis, suggesting that an active viral genome is necessary for induction.", "contents": "Induction of human cell DNA synthesis by herpes simplex virus type 2. The effect of herpes simplex virus type 2 (HSV-2) infection on the synthesis of DNA in human embryonic fibroblast cells was determined at temperatures permissive (37 C) and nonpermissive (42 C) for virus multiplication. During incubation of HSV-2 infected cultures at 42 C for 2 to 4 days or after shift-down from 42 to 37 C, incorporation of (3H)TdR into total DNA was increased 2-to 30-fold as compared with mock-infected cultures. Analysis of the (3H)DNA suggested that host cell DNA synthesis was induced by HSV-2 infection. Induction of host cell DNA synthesis by HSV-2 also occurred in cells arrested in DNA replication by low serum concentration. The three strains of HSV-2 tested were capable of stimulating cellular DNA synthesis. Virus inactivated by UV irradiation, heat, or neutral red dye and light did not induce cellular DNA synthesis, suggesting that an active viral genome is necessary for induction."} {"id": "PMID:163371", "title": "Phosphoproteins: structural components of oncornaviruses.", "content": "Oncornaviruses, which contain a virion-associated protein kinase, were found to possess phosphoproteins as virion structural components. One major phosphoprotein common to strains of laboratory and wild mouse oncornaviruses and a strain of feline leukemia virus was shown to be a polypeptide of about 12, 000 mol wt. In addition to this, the Kirsten strain of murine sarcoma virus contained a second major phosphoprotein of about 10, 000 mol wt, and mouse erythroblastosis virus contained a second major phosphoprotein that was either identical to or comigrated with the virion glycoprotein of about 74, 000 mol wt. The major phosphoprotein of RD-114 virus was found to be of about 16, 000 mol wt. The major phosphoamino acid of the 12, 000-mol wt polypeptide of the mouse erythroblastosis virus was identified as phosphoserine, and that of the 16, 000-mol wt polypeptide of the RD-114 virus was identified as phosphothreonine.", "contents": "Phosphoproteins: structural components of oncornaviruses. Oncornaviruses, which contain a virion-associated protein kinase, were found to possess phosphoproteins as virion structural components. One major phosphoprotein common to strains of laboratory and wild mouse oncornaviruses and a strain of feline leukemia virus was shown to be a polypeptide of about 12, 000 mol wt. In addition to this, the Kirsten strain of murine sarcoma virus contained a second major phosphoprotein of about 10, 000 mol wt, and mouse erythroblastosis virus contained a second major phosphoprotein that was either identical to or comigrated with the virion glycoprotein of about 74, 000 mol wt. The major phosphoprotein of RD-114 virus was found to be of about 16, 000 mol wt. The major phosphoamino acid of the 12, 000-mol wt polypeptide of the mouse erythroblastosis virus was identified as phosphoserine, and that of the 16, 000-mol wt polypeptide of the RD-114 virus was identified as phosphothreonine."} {"id": "PMID:163372", "title": "Interspersion of sequences in avian myeloblastosis virus rna that rapidly hybridize with leukemic chicken cell DNA.", "content": "Liquid hybridization of progressively smaller fragments (35S, 27S, 15.5S, 12.5S, and 8S) of poly(A)-selected avian myeloblastosis virus RNA with excess DNA from leukemic chicken myeloblasts revealed that all sizes of RNA contained sequences complementary to both slowly and rapidly hybridizing cellular DNA sequences. Apparently, the RNA sequences which hybridize rapidly with excesses of cellular DNA are not restricted to any one region of the avian myeloblastosis virus 35S RNA. Instead, they appear to be randomly distributed over the entire 35S avian myeloblastosis virus RNA molecule with some positioned within 200 nucleotides of the poly(A) tract at the 3' end of the RNA.", "contents": "Interspersion of sequences in avian myeloblastosis virus rna that rapidly hybridize with leukemic chicken cell DNA. Liquid hybridization of progressively smaller fragments (35S, 27S, 15.5S, 12.5S, and 8S) of poly(A)-selected avian myeloblastosis virus RNA with excess DNA from leukemic chicken myeloblasts revealed that all sizes of RNA contained sequences complementary to both slowly and rapidly hybridizing cellular DNA sequences. Apparently, the RNA sequences which hybridize rapidly with excesses of cellular DNA are not restricted to any one region of the avian myeloblastosis virus 35S RNA. Instead, they appear to be randomly distributed over the entire 35S avian myeloblastosis virus RNA molecule with some positioned within 200 nucleotides of the poly(A) tract at the 3' end of the RNA."} {"id": "PMID:163373", "title": "DNA of Epstein-Barr virus. I. Comparative studies of the DNA of Epstein-Barr virus from HR-1 and B95-8 cells: size, structure, and relatedness.", "content": "We have compared the properties of the DNA of Epstein-Barr virus (EBV) purified from HR-1 (EBV HR-1 DNA) and B95-8 (EBV B95-8 DNA) continuous lymphoblast cultures. Our data indicate that (i) the S suc of native EBV DNA relative to T4D DNA is 55S. Using the modified Burgi-Hershey relationship (5), we estimate the molecular weight of native EBV DNA is 101 (plus or minus the molecular weight of native FBV DNA by measurement of the length of 3) times 106. Estimation of the molecule relative to form II PM2 DNA yields a value of 105 (plus or minus 3) times 106. (ii) After alkali denaturation, less than 50% of EBV DNA sediments as a single band in alkaline sucrose gradients in the region expected for DNA of 50 times 406 daltons. (iii) Intact EBV HR-1 and EBV B 95-8 DNAs band at 1.718 g/cm3 and a smaller band (approximately 25% of the DNA) AT 1.720 G/CM3. (IV) EBV HR-1 DNA possesses greater than 97% of the sequences of EBV B95-8 DNA. Hybrid DNA molecules formed between (3H)EBV HR-1 DNA and EBV HR-1 DNA or EBV B95-8 DNA had identical thermal stability. EBV B95-8 DNA lacks approximately 15% of the DNA sequences of EBV HR-1 DNA. We interpret these data to mean that EBV B95-8 is derived from a parental EBV through loss of genetic complexity. This defect may be linked to the ability of EBV B95-8 to \"transform\" lymphocytes invitro.", "contents": "DNA of Epstein-Barr virus. I. Comparative studies of the DNA of Epstein-Barr virus from HR-1 and B95-8 cells: size, structure, and relatedness. We have compared the properties of the DNA of Epstein-Barr virus (EBV) purified from HR-1 (EBV HR-1 DNA) and B95-8 (EBV B95-8 DNA) continuous lymphoblast cultures. Our data indicate that (i) the S suc of native EBV DNA relative to T4D DNA is 55S. Using the modified Burgi-Hershey relationship (5), we estimate the molecular weight of native EBV DNA is 101 (plus or minus the molecular weight of native FBV DNA by measurement of the length of 3) times 106. Estimation of the molecule relative to form II PM2 DNA yields a value of 105 (plus or minus 3) times 106. (ii) After alkali denaturation, less than 50% of EBV DNA sediments as a single band in alkaline sucrose gradients in the region expected for DNA of 50 times 406 daltons. (iii) Intact EBV HR-1 and EBV B 95-8 DNAs band at 1.718 g/cm3 and a smaller band (approximately 25% of the DNA) AT 1.720 G/CM3. (IV) EBV HR-1 DNA possesses greater than 97% of the sequences of EBV B95-8 DNA. Hybrid DNA molecules formed between (3H)EBV HR-1 DNA and EBV HR-1 DNA or EBV B95-8 DNA had identical thermal stability. EBV B95-8 DNA lacks approximately 15% of the DNA sequences of EBV HR-1 DNA. We interpret these data to mean that EBV B95-8 is derived from a parental EBV through loss of genetic complexity. This defect may be linked to the ability of EBV B95-8 to \"transform\" lymphocytes invitro."} {"id": "PMID:163374", "title": "Simian virus 40 functions required for the establishment and maintenance of malignant transformation.", "content": "Members of the five classes of temperature-sensitive simian virus 40 mutants were tested for their ability to transform Chinese hamster lung cells. Two criteria for transformation were used: the ability to form clones in medium with low serum concentrations and the ability to overgrow a monolayer. Only A mutants failed to transform at the restrictive temperature when subconfluent Chinese hamster lung monolayers were used. However, both A and D mutants failed to transform at the restrictive temperature when confluent monolayers and depleted medium were used. When transformed clones were selected, purified by recloning, and examined at both temperatures, only cell lines induced by A mutants lost the transformed phenotype at the higher temperature. Thus, A function is required for maintenance of the transformed phenotype in Chinese hamster lung cells. A function is known to be required for the initiation of viral DNA synthesis in permissive cells. Therefore, transformation may be a consequence of the introduction into a cell of the capacity for aberrant initiation of DNA replication.", "contents": "Simian virus 40 functions required for the establishment and maintenance of malignant transformation. Members of the five classes of temperature-sensitive simian virus 40 mutants were tested for their ability to transform Chinese hamster lung cells. Two criteria for transformation were used: the ability to form clones in medium with low serum concentrations and the ability to overgrow a monolayer. Only A mutants failed to transform at the restrictive temperature when subconfluent Chinese hamster lung monolayers were used. However, both A and D mutants failed to transform at the restrictive temperature when confluent monolayers and depleted medium were used. When transformed clones were selected, purified by recloning, and examined at both temperatures, only cell lines induced by A mutants lost the transformed phenotype at the higher temperature. Thus, A function is required for maintenance of the transformed phenotype in Chinese hamster lung cells. A function is known to be required for the initiation of viral DNA synthesis in permissive cells. Therefore, transformation may be a consequence of the introduction into a cell of the capacity for aberrant initiation of DNA replication."} {"id": "PMID:163375", "title": "Function of simian virus 40 gene A in transforming infection.", "content": "In productive infection by simian virus 40, the A gene is known to regulate the initiation of viral DNA replication and to control the synthesis of late viral RNA. The function of the A gene in transforming infection was investigated by the infection of a variety of cell species with six independently isolated temperature-sensitive mutants belonging to the A complementation group. The A mutants failed to initiate the stable transformation of cells during continuous infection at the restrictive temperature. After the establishment of transformation at the permissive temperature and a subsequent shift to the restrictive temperature to block the A function, however, two distinct virus-cell interactions were identified. In one case, the increased colony-forming capacity of transformed cells remained stable after the temperature shift. In the other case, the temperature shift decreased the capacity of transformed cells to form colonies to the level of untransformed control cells. The outcome of the virus-cell interaction depended both on the nature of the A mutation in a given cell species and on the species of the cell transformed by a given mutant. These findings suggest that the transformation process may require two distinct events, each related to A gene expression.", "contents": "Function of simian virus 40 gene A in transforming infection. In productive infection by simian virus 40, the A gene is known to regulate the initiation of viral DNA replication and to control the synthesis of late viral RNA. The function of the A gene in transforming infection was investigated by the infection of a variety of cell species with six independently isolated temperature-sensitive mutants belonging to the A complementation group. The A mutants failed to initiate the stable transformation of cells during continuous infection at the restrictive temperature. After the establishment of transformation at the permissive temperature and a subsequent shift to the restrictive temperature to block the A function, however, two distinct virus-cell interactions were identified. In one case, the increased colony-forming capacity of transformed cells remained stable after the temperature shift. In the other case, the temperature shift decreased the capacity of transformed cells to form colonies to the level of untransformed control cells. The outcome of the virus-cell interaction depended both on the nature of the A mutation in a given cell species and on the species of the cell transformed by a given mutant. These findings suggest that the transformation process may require two distinct events, each related to A gene expression."} {"id": "PMID:163376", "title": "Role of simian virus 40 gene A function in maintenance of transformation.", "content": "Mouse, hamster, and human cells were transformed at the permissive temperature by mutants from simian virus 40 (SV40) complementation group A in order to ascertain the role of the gene A function in transformation. The following parameters of transformation were monitored with the transformed cells under permissive and nonpermissive conditions: morphology; saturation density; colony formation on plastic, on cell monolayers, and in soft agar; uptake of hexose; and the expression of SV40 tumor (T) and surface (S) antigens. Cells transformed by the temperature-sensitive (ts) mutants exhibited the phenotype of transformed cells at the nonrestrictive temperature for all of the parameters studied. However, when grown at the restrictive temperature, they were phenotypically similar to normal, untransformed cells. Growth curves showed that the (ts) A mutant-transformed cells exhibited the growth characteristics of wild-type virus-transformed cells at the permissive temperature and resembled normal cells when placed under restrictive conditions. There were 3-to 51-fold reductions in the levels of saturation density, colony formation, and uptake of hexose when the mutant-transformed cells were the elevated temperature as compared to when they were grown at the permissive temperature. Mutant-transformed cells from the nonpermissive temperature were able to produce transformed foci when shifted down to permissive conditions, indicating that the phenotypically reverted cells were still viable and that the reversion was a reversible event. SV40 T antigen was present in the cells at both temperatures, but S antigen was not detected in cells maintained at the nonpremissive temperature. All of the wild-type virus-transformed cells exhbited a transformed cells exhibited a transformed phenotype when grown under either restrictive or nonrestrictive conditions. Thers results indicate that the SV40 group A mutant-transformed cells are temperature sensitive for the maintenance of growth properties characteristics of transformation. Virus rescued from the mutant-transformed cells by the transfection method was ts, suggesting that the SV40 gene A function, rather than a cellular one, is responsible for the ts behavior of the cells.", "contents": "Role of simian virus 40 gene A function in maintenance of transformation. Mouse, hamster, and human cells were transformed at the permissive temperature by mutants from simian virus 40 (SV40) complementation group A in order to ascertain the role of the gene A function in transformation. The following parameters of transformation were monitored with the transformed cells under permissive and nonpermissive conditions: morphology; saturation density; colony formation on plastic, on cell monolayers, and in soft agar; uptake of hexose; and the expression of SV40 tumor (T) and surface (S) antigens. Cells transformed by the temperature-sensitive (ts) mutants exhibited the phenotype of transformed cells at the nonrestrictive temperature for all of the parameters studied. However, when grown at the restrictive temperature, they were phenotypically similar to normal, untransformed cells. Growth curves showed that the (ts) A mutant-transformed cells exhibited the growth characteristics of wild-type virus-transformed cells at the permissive temperature and resembled normal cells when placed under restrictive conditions. There were 3-to 51-fold reductions in the levels of saturation density, colony formation, and uptake of hexose when the mutant-transformed cells were the elevated temperature as compared to when they were grown at the permissive temperature. Mutant-transformed cells from the nonpermissive temperature were able to produce transformed foci when shifted down to permissive conditions, indicating that the phenotypically reverted cells were still viable and that the reversion was a reversible event. SV40 T antigen was present in the cells at both temperatures, but S antigen was not detected in cells maintained at the nonpremissive temperature. All of the wild-type virus-transformed cells exhbited a transformed cells exhibited a transformed phenotype when grown under either restrictive or nonrestrictive conditions. Thers results indicate that the SV40 group A mutant-transformed cells are temperature sensitive for the maintenance of growth properties characteristics of transformation. Virus rescued from the mutant-transformed cells by the transfection method was ts, suggesting that the SV40 gene A function, rather than a cellular one, is responsible for the ts behavior of the cells."} {"id": "PMID:163377", "title": "Simian virus 40 gene A function and maintenance of transformation.", "content": "Transformants have been isolated after infection of rat embryo cells at 33 C with either wild-type simian virus 40 or with the temperature-sensitive gene A mutants, tsA7 and tsA28. Examination of properties usually associated with transformation such as growth in 1% serum, growth rate, saturation density, and morphology show that these properties are temperature dependent in the tsA transformants characterized, but are not temperature dependent in the wild-type transformants that have been examined. In the most thoroughly characterized tsA transformants the expression of T antigen also appears to be temperature dependent. These data suggest that an active A function is required for the maintenance of transformation in these cells. In the lytic cycle, the A function is involved in the initiation of DNA synthesis. Thus transformation by simian virus 40 may be the direct consequence of the introduction of the simian virus 40 replicon and the presence of its DNA initiator function, which causes the cell to express a transformed phenotype.", "contents": "Simian virus 40 gene A function and maintenance of transformation. Transformants have been isolated after infection of rat embryo cells at 33 C with either wild-type simian virus 40 or with the temperature-sensitive gene A mutants, tsA7 and tsA28. Examination of properties usually associated with transformation such as growth in 1% serum, growth rate, saturation density, and morphology show that these properties are temperature dependent in the tsA transformants characterized, but are not temperature dependent in the wild-type transformants that have been examined. In the most thoroughly characterized tsA transformants the expression of T antigen also appears to be temperature dependent. These data suggest that an active A function is required for the maintenance of transformation in these cells. In the lytic cycle, the A function is involved in the initiation of DNA synthesis. Thus transformation by simian virus 40 may be the direct consequence of the introduction of the simian virus 40 replicon and the presence of its DNA initiator function, which causes the cell to express a transformed phenotype."} {"id": "PMID:163378", "title": "Formation of nucleoprotein complexes between polyoma empty capsides and DNA.", "content": "Purified polyoma empty capsids and polyoma type I DNA interact in a cell-free system to form nucleoprotein complexes. Complexes that consist of one, two, three, and four empty capsids per DNA molecule have been detected. Polyoma virions or capsomers do not react with added DNA to form such complexes.", "contents": "Formation of nucleoprotein complexes between polyoma empty capsides and DNA. Purified polyoma empty capsids and polyoma type I DNA interact in a cell-free system to form nucleoprotein complexes. Complexes that consist of one, two, three, and four empty capsids per DNA molecule have been detected. Polyoma virions or capsomers do not react with added DNA to form such complexes."} {"id": "PMID:163379", "title": "Detection of a virus-specific antigen on the surface of herpes simplex virus-transformed cells.", "content": "A virion-associated antigen, CP-1, was detected on the surface of hamster cells after transformation by inactivated herpes simplex virus type 1. Presence of the CP-1 antigen on the cells correlates with the synthesis of antibody by tumorbearing hamsters capable of neutralizing both herpes simplex virus types 1 and 2.", "contents": "Detection of a virus-specific antigen on the surface of herpes simplex virus-transformed cells. A virion-associated antigen, CP-1, was detected on the surface of hamster cells after transformation by inactivated herpes simplex virus type 1. Presence of the CP-1 antigen on the cells correlates with the synthesis of antibody by tumorbearing hamsters capable of neutralizing both herpes simplex virus types 1 and 2."} {"id": "PMID:163380", "title": "Ectopic production of erythropoietin in Wilms tumor patients in relation to clinical stage and disease activity.", "content": "Measurement of erythropoietin levels was achieved in urine, plasma and tumor extract specimens in 27 Wilms tumor patients. Good correlation of the stage of the disease, the clinical judgment of inactive or responding tumor foci and erythropoietin levels was noted. Erythropoietin levels are believed to reflect ectopic hormone production by the primary or secondary tumor. Since the erythropoietin hormone assayed in these and other Wilms tumor patients was not associated with polycythemia, it is believed that Wilms tumor-associated erythropoietin differs in some manner from the hormone produced normally in man and possible in other states associated with secondary polycythemia. Etythropoietin assay with further purification and technical development can be of additional widespread assistance in the clinical classification and subsequent management of the tumor state. Our study confirms this biological potential.", "contents": "Ectopic production of erythropoietin in Wilms tumor patients in relation to clinical stage and disease activity. Measurement of erythropoietin levels was achieved in urine, plasma and tumor extract specimens in 27 Wilms tumor patients. Good correlation of the stage of the disease, the clinical judgment of inactive or responding tumor foci and erythropoietin levels was noted. Erythropoietin levels are believed to reflect ectopic hormone production by the primary or secondary tumor. Since the erythropoietin hormone assayed in these and other Wilms tumor patients was not associated with polycythemia, it is believed that Wilms tumor-associated erythropoietin differs in some manner from the hormone produced normally in man and possible in other states associated with secondary polycythemia. Etythropoietin assay with further purification and technical development can be of additional widespread assistance in the clinical classification and subsequent management of the tumor state. Our study confirms this biological potential."} {"id": "PMID:163381", "title": "Testicular atrophy in Columbian black-tailed deer in California.", "content": "During an 18-year period, 4.1% (34/831) of male deer (Odocoileus hemionus columbianus) killed on a field station during the autumn hunting season had velvet-covered, often misshapen antlers, and at least two deer had testicular atrophy (gonads from most deer were not available for examination). Testes from six similarly affected deer and several normal deer were compared histologically. Lesions ranged from hypocellularity of the semeniferous tubules and relative hyperplasia or degeneration of interstitial cells to complete connective tissue replacement of the testicular parencyma. Chronic vascular changes were present in several testes. The etiology and pathogenesis of the lesions were not determined.", "contents": "Testicular atrophy in Columbian black-tailed deer in California. During an 18-year period, 4.1% (34/831) of male deer (Odocoileus hemionus columbianus) killed on a field station during the autumn hunting season had velvet-covered, often misshapen antlers, and at least two deer had testicular atrophy (gonads from most deer were not available for examination). Testes from six similarly affected deer and several normal deer were compared histologically. Lesions ranged from hypocellularity of the semeniferous tubules and relative hyperplasia or degeneration of interstitial cells to complete connective tissue replacement of the testicular parencyma. Chronic vascular changes were present in several testes. The etiology and pathogenesis of the lesions were not determined."} {"id": "PMID:163382", "title": "Avian pox in Florida sandhill cranes.", "content": "Cutaneous elevations were present on the feet, legs and heads of four Florida sandhill cranes, Grus canadensis pratensis, (one free-living, three penreared birds). As a result of examination of the elevations by light- and electron microscopy, it was determined that the lesions were caused by poxvirus. This is the first record of pox in cranes in North America.", "contents": "Avian pox in Florida sandhill cranes. Cutaneous elevations were present on the feet, legs and heads of four Florida sandhill cranes, Grus canadensis pratensis, (one free-living, three penreared birds). As a result of examination of the elevations by light- and electron microscopy, it was determined that the lesions were caused by poxvirus. This is the first record of pox in cranes in North America."} {"id": "PMID:163383", "title": "Inclusion body disease (herpesvirus infection) of falcons (IBDF).", "content": "Inclusion body disease of falcons (IBDF) is caused by a herpesvirus. The clinical course is short, 24 to 72 hours in duration, and is characterized by mild to severe depression and weakness often accompanied by anorexia. The disease is invariably fatal. The virus has a marked affinity for the reticuloendothelial system and hepatocytes,producing focal to diffuse necrosis of infected tissues accompanied by the formation of intranuclear inclusion bodies. The virus is pathogenic for American kestrels (Falco sparverius) and great horned owls (Bubo virginianus) in which typical lesions of IBDF are reproduced. The lesions of IBDF are similar to those produced by some herpesvirus infections in other avian species.", "contents": "Inclusion body disease (herpesvirus infection) of falcons (IBDF). Inclusion body disease of falcons (IBDF) is caused by a herpesvirus. The clinical course is short, 24 to 72 hours in duration, and is characterized by mild to severe depression and weakness often accompanied by anorexia. The disease is invariably fatal. The virus has a marked affinity for the reticuloendothelial system and hepatocytes,producing focal to diffuse necrosis of infected tissues accompanied by the formation of intranuclear inclusion bodies. The virus is pathogenic for American kestrels (Falco sparverius) and great horned owls (Bubo virginianus) in which typical lesions of IBDF are reproduced. The lesions of IBDF are similar to those produced by some herpesvirus infections in other avian species."} {"id": "PMID:163384", "title": "Inclusion body disease in a great horned owl.", "content": "The carcass of a great horned owl (Bubo virginianus), which had been found moribund in southern Ontario, was presented for necropsy. Throughout the liver and spleen were numerous white foci 1-2 mm in diameter; also noted were white plaques in the mucosae of the pharyngeal papillae and intestine. Results of light and electron microscopic studies and experimental transmission to two captive great horned owls suggested that this was a herpvirus disease similar and possibly indentical to the owl disease reported by other workers in Wiconsin and Australia.", "contents": "Inclusion body disease in a great horned owl. The carcass of a great horned owl (Bubo virginianus), which had been found moribund in southern Ontario, was presented for necropsy. Throughout the liver and spleen were numerous white foci 1-2 mm in diameter; also noted were white plaques in the mucosae of the pharyngeal papillae and intestine. Results of light and electron microscopic studies and experimental transmission to two captive great horned owls suggested that this was a herpvirus disease similar and possibly indentical to the owl disease reported by other workers in Wiconsin and Australia."} {"id": "PMID:163386", "title": "Ascorbic acid for the common cold. A prophylactic and therapeutic trial.", "content": "Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid. One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid. Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind.", "contents": "Ascorbic acid for the common cold. A prophylactic and therapeutic trial. Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid. One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid. Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind."} {"id": "PMID:163389", "title": "Renal action of cholera toxin: I. Effects on urinary excretion of electrolytes and cyclic AMP.", "content": "The infusion of cholera toxin (CT), 4 mug/min, into one renal artery of normal and thyroparathyroidectomized (T-PTX) dogs produced ipsilateral increments in the excretion of Na, K, Ca, Mg and Cl. Phosphate excretion increased from both kidneys, but more from the infused kidney in intact dogs. Unilateral phosphaturia occurred in T-PTX dogs studied five or more days after T-PTX. The changes in electrolyte excretion appeared 40 to 80 min after initiation of CT infusion and the maximal effects were noted after 100 to 140 min. The effects of CT on electrolyte excretion could not be accounted for by changes in glomerular filtration rate or renal plasma flow. Urinary cyclic adenosine monophosphate (AMP) increased from both kidneys but slightly more from the infused kidney. Adenylate cyclase activity of cortex and outer medulla of the infused kidney was 109 to 142% higher than that of the control kidney. The results indicate that CT decreases the net transport of various electrolytes by the renal tubule. This effect is probably mediated by the activation of renal adenylate cyclase(s) sensitive to the enterotoxin.", "contents": "Renal action of cholera toxin: I. Effects on urinary excretion of electrolytes and cyclic AMP. The infusion of cholera toxin (CT), 4 mug/min, into one renal artery of normal and thyroparathyroidectomized (T-PTX) dogs produced ipsilateral increments in the excretion of Na, K, Ca, Mg and Cl. Phosphate excretion increased from both kidneys, but more from the infused kidney in intact dogs. Unilateral phosphaturia occurred in T-PTX dogs studied five or more days after T-PTX. The changes in electrolyte excretion appeared 40 to 80 min after initiation of CT infusion and the maximal effects were noted after 100 to 140 min. The effects of CT on electrolyte excretion could not be accounted for by changes in glomerular filtration rate or renal plasma flow. Urinary cyclic adenosine monophosphate (AMP) increased from both kidneys but slightly more from the infused kidney. Adenylate cyclase activity of cortex and outer medulla of the infused kidney was 109 to 142% higher than that of the control kidney. The results indicate that CT decreases the net transport of various electrolytes by the renal tubule. This effect is probably mediated by the activation of renal adenylate cyclase(s) sensitive to the enterotoxin."} {"id": "PMID:163417", "title": "The granulovesicular bodies of the arterial wall.", "content": "Small, round, membrane-bound electron-dense bodies were observed in the smooth muscle cells and the intimal and medial intercellular spaces of arteries in the dog, rat, and pig under normal and various experimental conditions. These structures, referred to as granulovesicular bodies (GVB), measured from 0.2 to 0.5 mum. in diameter and contained an inner core of granular and vesicular subunits. The intercellular and extracellular forms of the GVB were structurally similar, and in the interstitial spaces they appeared to have a definite spatial relation to the elements of elastic tissue. The GVB were more numerous under experimental than under normal conditions. It is speculated that the GVB are secretory in nature, originating from the smooth muscle cells, and may play a role in the remodeling of arterial elastic fibers.", "contents": "The granulovesicular bodies of the arterial wall. Small, round, membrane-bound electron-dense bodies were observed in the smooth muscle cells and the intimal and medial intercellular spaces of arteries in the dog, rat, and pig under normal and various experimental conditions. These structures, referred to as granulovesicular bodies (GVB), measured from 0.2 to 0.5 mum. in diameter and contained an inner core of granular and vesicular subunits. The intercellular and extracellular forms of the GVB were structurally similar, and in the interstitial spaces they appeared to have a definite spatial relation to the elements of elastic tissue. The GVB were more numerous under experimental than under normal conditions. It is speculated that the GVB are secretory in nature, originating from the smooth muscle cells, and may play a role in the remodeling of arterial elastic fibers."} {"id": "PMID:163418", "title": "Cytoplasmic inclusions in pulmonary macrophages of cigarette smokers.", "content": "Alveolar and bronchiolar spaces in the lungs of cigarette smokers usually contain numerous macrophages with pigmented cytoplasmic granules. By electron microscopy the pigmentation appears to be due, at least in part, to increased numbers of lysosomes and phagolysosomes. Within these cytoplasmic organelles, structures are found which we designate \"smokers' inclusions\", since they are observed exclusively in the interstitial and alveolar macrophages of cigarette users. The inclusions have been referred to by other investigators as \"needle-shaped\" and \"fiber-like\". Since cross-sections of the structures are never seen in electron micrographs, a fiber or needle shape seems unlikely. On the other hand, thin sectioning techniques impart varying lengths to the inclusions, suggesting that they have a disc, or platelet, configuration. Surgically resected lung tissue from smokers and nonsmokers was digested in hot potassium hydroxide. Digestates contained varying numbers of hexagonal platelike particles which had features consistent with those of the aluminum silicate kaolinite, and energy-dispersive x-ray spectrometry confirmed the presence of these two elements. The origin of aluminum silicate inclusions in pulmonary macrophages has yet to be determined, although preliminary evidence strongly suggests that they are derived from inhaled tobacco smoke. The cytotoxicity of kaolinite in vitro and the possible role of aluminum silicate crystals in the pathogenesis of pulmonary fibrosis are discussed.", "contents": "Cytoplasmic inclusions in pulmonary macrophages of cigarette smokers. Alveolar and bronchiolar spaces in the lungs of cigarette smokers usually contain numerous macrophages with pigmented cytoplasmic granules. By electron microscopy the pigmentation appears to be due, at least in part, to increased numbers of lysosomes and phagolysosomes. Within these cytoplasmic organelles, structures are found which we designate \"smokers' inclusions\", since they are observed exclusively in the interstitial and alveolar macrophages of cigarette users. The inclusions have been referred to by other investigators as \"needle-shaped\" and \"fiber-like\". Since cross-sections of the structures are never seen in electron micrographs, a fiber or needle shape seems unlikely. On the other hand, thin sectioning techniques impart varying lengths to the inclusions, suggesting that they have a disc, or platelet, configuration. Surgically resected lung tissue from smokers and nonsmokers was digested in hot potassium hydroxide. Digestates contained varying numbers of hexagonal platelike particles which had features consistent with those of the aluminum silicate kaolinite, and energy-dispersive x-ray spectrometry confirmed the presence of these two elements. The origin of aluminum silicate inclusions in pulmonary macrophages has yet to be determined, although preliminary evidence strongly suggests that they are derived from inhaled tobacco smoke. The cytotoxicity of kaolinite in vitro and the possible role of aluminum silicate crystals in the pathogenesis of pulmonary fibrosis are discussed."} {"id": "PMID:163419", "title": "Lead-induced inclusion bodies: results of ethylenediaminetetraacetic acid treatment.", "content": "Earlier studies have shown that lead-induced nuclear inclusion bodies are composed of a lead-protein complex. Twenty-four hours after treatment of a lead-poisoned rat with a single dose of ethylenediaminetetraacetic acid (EDTA), urinary excretion of lead is maximally increased and the lead content of the kidneys is significantly decreased. Inclusion bodies in renal cell nuclei at this time are found in various stages of dissolution and migration out of the nucleus. The outer fibrillary margin becomes loosened, and slight disruption occurs at the periphery of the inclusion. Some inclusion bodies appear to be moving through the nuclear membrane. There is an invagination of both inner and outer nuclear membranes. Numerous cytoplasmic vacuoles occur which contain fibrillar material resembling portions of intact nuclear inclusions. Kidney nuclei of rats 24 hours after three daily injections of EDTA have no inclusion bodies. Whether the nuclear-cytoplasmic exchange occurs by dilation of a nuclear pore or by another mode of separation of nuclear membranes cannot be determined. This experiment demonstrates that nuclear inclusion bodies formed in lead poisoning are disrupted and removed from the nuclei by the administration of EDTA. This change corresponds with peak urinary excretion of lead. The sharp increase in urinary lead following EDTA therapy must reflect, at least in part, chelation and excretion of sequestered lead bound to nuclear protein.", "contents": "Lead-induced inclusion bodies: results of ethylenediaminetetraacetic acid treatment. Earlier studies have shown that lead-induced nuclear inclusion bodies are composed of a lead-protein complex. Twenty-four hours after treatment of a lead-poisoned rat with a single dose of ethylenediaminetetraacetic acid (EDTA), urinary excretion of lead is maximally increased and the lead content of the kidneys is significantly decreased. Inclusion bodies in renal cell nuclei at this time are found in various stages of dissolution and migration out of the nucleus. The outer fibrillary margin becomes loosened, and slight disruption occurs at the periphery of the inclusion. Some inclusion bodies appear to be moving through the nuclear membrane. There is an invagination of both inner and outer nuclear membranes. Numerous cytoplasmic vacuoles occur which contain fibrillar material resembling portions of intact nuclear inclusions. Kidney nuclei of rats 24 hours after three daily injections of EDTA have no inclusion bodies. Whether the nuclear-cytoplasmic exchange occurs by dilation of a nuclear pore or by another mode of separation of nuclear membranes cannot be determined. This experiment demonstrates that nuclear inclusion bodies formed in lead poisoning are disrupted and removed from the nuclei by the administration of EDTA. This change corresponds with peak urinary excretion of lead. The sharp increase in urinary lead following EDTA therapy must reflect, at least in part, chelation and excretion of sequestered lead bound to nuclear protein."} {"id": "PMID:163425", "title": "A plasma inhibitor of the renin-antirenin reaction and the in vitro generation of angiotensin I.", "content": "In the course of studies designed to develop a radioimmunoassay system for the detection of renin, we have identified in human plasma a potent inhibitor that interferes with the renin-antirenin reaction. Utilizing gel filtration, this renin-antirenin inhibitory activity was found to have the same molecular size as renin substrate. However, it could be separated from renin substrate by ion-exchange chromatography. When fractions containing this activity were tested in an in vitro system containing renin and renin substrate, they were found to inhibit the generation of angiotensin I.", "contents": "A plasma inhibitor of the renin-antirenin reaction and the in vitro generation of angiotensin I. In the course of studies designed to develop a radioimmunoassay system for the detection of renin, we have identified in human plasma a potent inhibitor that interferes with the renin-antirenin reaction. Utilizing gel filtration, this renin-antirenin inhibitory activity was found to have the same molecular size as renin substrate. However, it could be separated from renin substrate by ion-exchange chromatography. When fractions containing this activity were tested in an in vitro system containing renin and renin substrate, they were found to inhibit the generation of angiotensin I."} {"id": "PMID:163436", "title": "Transfusion-associated hepatitis not due to viral hepatitis type A or B.", "content": "Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.", "contents": "Transfusion-associated hepatitis not due to viral hepatitis type A or B. Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified."} {"id": "PMID:163448", "title": "Computerized axial tomography: clinicopathologic correlation.", "content": "Between August 1973 and April 1974 more than 750 patients had computerized axial tomography (CT) scans at the Massachusetts General Hospital. Ten brains from previously CT-scanned patients in this group were sectioned in the plane of the scan. Nearly exact correlation was found between the anatomic location and extent of intracranial lesions demonstrated by CT scan and the findings on gross and microscopic pathologic examination in cases of primary intracranial tumors, obstructive hydrocephalus, intracerebral hemorrhage, ischemic and hemorrhagic infarctions, pineal tumor, and thermal-burn encephalopathy. Determination of absorption values (mu) of 47 pathologically verified processes showed that high-absorption intracerebral hemorrhage and calcium-containing tumors are readily separable from other processes on the basis of mu values alone. However, the abnormal mu values of primary brain tumor, edema, and infarction are difficult to distinguish from those of normal spinal fluid and white matter.", "contents": "Computerized axial tomography: clinicopathologic correlation. Between August 1973 and April 1974 more than 750 patients had computerized axial tomography (CT) scans at the Massachusetts General Hospital. Ten brains from previously CT-scanned patients in this group were sectioned in the plane of the scan. Nearly exact correlation was found between the anatomic location and extent of intracranial lesions demonstrated by CT scan and the findings on gross and microscopic pathologic examination in cases of primary intracranial tumors, obstructive hydrocephalus, intracerebral hemorrhage, ischemic and hemorrhagic infarctions, pineal tumor, and thermal-burn encephalopathy. Determination of absorption values (mu) of 47 pathologically verified processes showed that high-absorption intracerebral hemorrhage and calcium-containing tumors are readily separable from other processes on the basis of mu values alone. However, the abnormal mu values of primary brain tumor, edema, and infarction are difficult to distinguish from those of normal spinal fluid and white matter."} {"id": "PMID:163449", "title": "Biochemical mapping of the noradrenergic projection from the locus coeruleus. A model for studies of brain neuronal pathways.", "content": "Mapping of the noradrenergic projection from neurons in the rat locus coeruleus has been examined by combining a sensitive radioisotopic assay for catecholamines with a microdissection technique to remove multiple separate brain nuclei. The effect of a unilateral locus coeruleus lesion on norepinephrine concentration in 19 brain regions ipsilateral and contralateral to the lesion was determined. Evidence for ipsilateral and bilateral innervation to specific regions is presented, and many regions appear to receive combined innervation from other noradrenergic loci, in addition to that from the locus coeruleus. Fluorescence rating was correlated with biochemical measurement of amine content with these techniques and proportionality was observed over a narrow range. With this proportionality taken into consideration, mapping results obtained by biochemical and fluorescence methods are compared.", "contents": "Biochemical mapping of the noradrenergic projection from the locus coeruleus. A model for studies of brain neuronal pathways. Mapping of the noradrenergic projection from neurons in the rat locus coeruleus has been examined by combining a sensitive radioisotopic assay for catecholamines with a microdissection technique to remove multiple separate brain nuclei. The effect of a unilateral locus coeruleus lesion on norepinephrine concentration in 19 brain regions ipsilateral and contralateral to the lesion was determined. Evidence for ipsilateral and bilateral innervation to specific regions is presented, and many regions appear to receive combined innervation from other noradrenergic loci, in addition to that from the locus coeruleus. Fluorescence rating was correlated with biochemical measurement of amine content with these techniques and proportionality was observed over a narrow range. With this proportionality taken into consideration, mapping results obtained by biochemical and fluorescence methods are compared."} {"id": "PMID:163450", "title": "Peripheral neuropathy in classic Niemann-Pick disease: ultrastructure of nerves and skeletal muscles.", "content": "A patient with classic (type A) Niemann-Pick disease had the usual clinical signs of failure to thrive, hepatosplenomegaly, and intellectual deterioration in the first year of life. In addition, there was striking hypotonia, areflexia, and abnormal nerve conduction velocities. Pathologically, the Schwann cells were filled with numerous cytoplasmic bodies. These bodies measured 1 mu in diameter and appeared to be dense, round masses with poorly defined internal structure but with occasional slightly curved parallel lines and small radiolucent areas. Peripheral nerve involvement may be a frequent finding in patients with classic Niemann-Pick disease.", "contents": "Peripheral neuropathy in classic Niemann-Pick disease: ultrastructure of nerves and skeletal muscles. A patient with classic (type A) Niemann-Pick disease had the usual clinical signs of failure to thrive, hepatosplenomegaly, and intellectual deterioration in the first year of life. In addition, there was striking hypotonia, areflexia, and abnormal nerve conduction velocities. Pathologically, the Schwann cells were filled with numerous cytoplasmic bodies. These bodies measured 1 mu in diameter and appeared to be dense, round masses with poorly defined internal structure but with occasional slightly curved parallel lines and small radiolucent areas. Peripheral nerve involvement may be a frequent finding in patients with classic Niemann-Pick disease."} {"id": "PMID:163451", "title": "Myopathy associated with linear scleroderma. A histochemical and electron microscopic study.", "content": "Pathologic findings in biopsied rectus femoris muscle underlying an area of linear scleroderma are described. The affected muscle was weak and atrophic. On electromyography it showed motor unit potentials of decreased amplitude and duration. Light microscopic changes were minimal. There was atrophy of some histochemical type I fibers. More prominent changes were found at the ultrastructural level, where many of the capillary basal laminae were thickened and reduplicated. Most striking was the presence of two types of electron-dense, rounded inclusions within the mitochondria, one ranging from 29 to 47nm in diameter and the other from 54 to 131 nm in diameter.", "contents": "Myopathy associated with linear scleroderma. A histochemical and electron microscopic study. Pathologic findings in biopsied rectus femoris muscle underlying an area of linear scleroderma are described. The affected muscle was weak and atrophic. On electromyography it showed motor unit potentials of decreased amplitude and duration. Light microscopic changes were minimal. There was atrophy of some histochemical type I fibers. More prominent changes were found at the ultrastructural level, where many of the capillary basal laminae were thickened and reduplicated. Most striking was the presence of two types of electron-dense, rounded inclusions within the mitochondria, one ranging from 29 to 47nm in diameter and the other from 54 to 131 nm in diameter."} {"id": "PMID:163452", "title": "Human muscle fiber fine structure: morphometric data on controls.", "content": "Muscle fiber fine structure was quantitatively analyzed in 70 longitudinally and 65 transversely sectioned fibers from 10 control subjects without weakness. The average mitochondrial fraction of the fiber volume is close to 4 percent and the mean size of a mitochondrion is about 0.1 mum2. The sarcotubular surface area per unit fiber volume is close to 1.5 mum2/mum3 in transverse sections and 0.65 times this value in longitudinal sections. Only one-third of all fibers contain lipid droplets in the sectioned plane, and for all fibers the droplets account for approximately 0.12 percent of the fiber volume. Variations with the age and sex of the subjects and with different muscles were analyzed and the feasibility of typing human muscle fibers at the ultrastructural level was evaluated.", "contents": "Human muscle fiber fine structure: morphometric data on controls. Muscle fiber fine structure was quantitatively analyzed in 70 longitudinally and 65 transversely sectioned fibers from 10 control subjects without weakness. The average mitochondrial fraction of the fiber volume is close to 4 percent and the mean size of a mitochondrion is about 0.1 mum2. The sarcotubular surface area per unit fiber volume is close to 1.5 mum2/mum3 in transverse sections and 0.65 times this value in longitudinal sections. Only one-third of all fibers contain lipid droplets in the sectioned plane, and for all fibers the droplets account for approximately 0.12 percent of the fiber volume. Variations with the age and sex of the subjects and with different muscles were analyzed and the feasibility of typing human muscle fibers at the ultrastructural level was evaluated."} {"id": "PMID:163453", "title": "Isolation of herpes simplex virus from the cerebrospinal fluid in viral meningitis.", "content": "Two cases of meningitis are reported in which the etiologic diagnosis was established by isolation of herpes simplex virus from the cerebrospinal fluid. Both patients were afebrile and had bradycardia when the cultures were obtained, and one patient had been thought to have leukemic meningitis. This experience added to that of others in the literature indicates the value of culture for herpes simplex virus in the cerebrospinal fluid.", "contents": "Isolation of herpes simplex virus from the cerebrospinal fluid in viral meningitis. Two cases of meningitis are reported in which the etiologic diagnosis was established by isolation of herpes simplex virus from the cerebrospinal fluid. Both patients were afebrile and had bradycardia when the cultures were obtained, and one patient had been thought to have leukemic meningitis. This experience added to that of others in the literature indicates the value of culture for herpes simplex virus in the cerebrospinal fluid."} {"id": "PMID:163455", "title": "[Study of the action of tolbutamide on the hypothalamo-hypophyseal-adrenocortical system in normal and obese subjects].", "content": "Changes in plasma cortisol during the tolbutamide test were evaluated in normal subjects and in obese patients with a normal (D = 60,1 plus or minus 8,3) or reduced (D = 23,2 plus or minus 9,5) blood sugar decrease coefficient. Increases were noted in normal subjects (from 14,0 plus or minus plus or minus 2,9 mug/100 ml to 25,5 plus or minus 11,5 mug/100 ml) or in obese patients with normal D (from 15,7 plus or minus 5,1 mug/100 ml to 25,9 plus or minus 9,2 mug/100 ml), while no significant variations were observed in patients with depressed D. Though a direct corticosteroidogenetic effect and/or interference with liver metabolisation of cortisol (and increased clearance) cannot be excluded, the data suggest that increased blood cortisol following tolbutamide is secondary to the lowering blood sugar action of the drug.", "contents": "[Study of the action of tolbutamide on the hypothalamo-hypophyseal-adrenocortical system in normal and obese subjects]. Changes in plasma cortisol during the tolbutamide test were evaluated in normal subjects and in obese patients with a normal (D = 60,1 plus or minus 8,3) or reduced (D = 23,2 plus or minus 9,5) blood sugar decrease coefficient. Increases were noted in normal subjects (from 14,0 plus or minus plus or minus 2,9 mug/100 ml to 25,5 plus or minus 11,5 mug/100 ml) or in obese patients with normal D (from 15,7 plus or minus 5,1 mug/100 ml to 25,9 plus or minus 9,2 mug/100 ml), while no significant variations were observed in patients with depressed D. Though a direct corticosteroidogenetic effect and/or interference with liver metabolisation of cortisol (and increased clearance) cannot be excluded, the data suggest that increased blood cortisol following tolbutamide is secondary to the lowering blood sugar action of the drug."} {"id": "PMID:163457", "title": "Effect of exogenous estrogen on serum pregnenolone, cortisol, and androgens in postmenopausal women.", "content": "Previous studies from this laboratory have included reports on the serum concentrations of the following steroids in premenopausal and postmenopausal women: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, cortisol, corticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, estone, and estradiol 17-beta. In general the steroid levels were lower in postmenopausal subjects, and this difference was significant at P smaller than 0.05 for 8 of the steroids. The significantly decreased peripheral level of steroids in the postmenopausal state can be explained by decreases either in ovarian secretion of steroids or in ovarian stimulation of the adrenal cortex. Since the contribution of the adrenal cortex to the peripheral levels of dehydroepiandrosterone sulfate (DHEA-S) is greater than 95% in premenopausal women, a plausible explanation for the marked drop observed in peripheral DHEA-S levels after menopause is that the ovary influences the steroidogenic activity of the adrenal cortex. In such cases a decrease in the stimulation of the adrenal cortex by some ovarian steroids would be expected. Estrogen therapy in 10 postmenopausal women resulted in significant increases in the serum levels of 3 of the steroids compared to those in untreated subjects, confirming the postulate that ovarian estrogens stimulate the secretion of adrenal androgens.", "contents": "Effect of exogenous estrogen on serum pregnenolone, cortisol, and androgens in postmenopausal women. Previous studies from this laboratory have included reports on the serum concentrations of the following steroids in premenopausal and postmenopausal women: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, cortisol, corticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, estone, and estradiol 17-beta. In general the steroid levels were lower in postmenopausal subjects, and this difference was significant at P smaller than 0.05 for 8 of the steroids. The significantly decreased peripheral level of steroids in the postmenopausal state can be explained by decreases either in ovarian secretion of steroids or in ovarian stimulation of the adrenal cortex. Since the contribution of the adrenal cortex to the peripheral levels of dehydroepiandrosterone sulfate (DHEA-S) is greater than 95% in premenopausal women, a plausible explanation for the marked drop observed in peripheral DHEA-S levels after menopause is that the ovary influences the steroidogenic activity of the adrenal cortex. In such cases a decrease in the stimulation of the adrenal cortex by some ovarian steroids would be expected. Estrogen therapy in 10 postmenopausal women resulted in significant increases in the serum levels of 3 of the steroids compared to those in untreated subjects, confirming the postulate that ovarian estrogens stimulate the secretion of adrenal androgens."} {"id": "PMID:163459", "title": "Bell's palsy associated with acute herpetic gingivostomatitis.", "content": "One of the most recent hypotheses relative to the cause of Bell's palsy is that involving the latent herpes simplex virus. A case is presented in which the primary infection of the facial nerve by the herpes simplex virus could have been a factor in the unilateral facial paralysis.", "contents": "Bell's palsy associated with acute herpetic gingivostomatitis. One of the most recent hypotheses relative to the cause of Bell's palsy is that involving the latent herpes simplex virus. A case is presented in which the primary infection of the facial nerve by the herpes simplex virus could have been a factor in the unilateral facial paralysis."} {"id": "PMID:163460", "title": "The odontogenic adenomatoid tumor. A comprehensive study of twenty new cases.", "content": "Twenty new cases of odontogenic adenomatoid tumor are added to the literature, bringing the total number of reported cases to 152. The clinical, radiographic, and microscopic findings in these cases support the previously reported data for this lesion. The odontogenic adenomatoid tumor is a benign lesion which arises from residual odontogenic epithelium. It should be treated conservatively, as there is no indication that this lesion will recur. The histogenesis of this lesion, as well as the origin of the esinophilic droplet material, is discussed.", "contents": "The odontogenic adenomatoid tumor. A comprehensive study of twenty new cases. Twenty new cases of odontogenic adenomatoid tumor are added to the literature, bringing the total number of reported cases to 152. The clinical, radiographic, and microscopic findings in these cases support the previously reported data for this lesion. The odontogenic adenomatoid tumor is a benign lesion which arises from residual odontogenic epithelium. It should be treated conservatively, as there is no indication that this lesion will recur. The histogenesis of this lesion, as well as the origin of the esinophilic droplet material, is discussed."} {"id": "PMID:163461", "title": "Metastatic malignancy in the submandibular gland.", "content": "Metastatic disease in the major salivary glands has been observed and reported in the literature. Often the site of origin of the primary tumor is the skin or mucosal lining of the head and neck structures, and the primary tumors most commonly are melanomas or squamous-cell carcinomas. The most frequently involved salivary gland is the parotid. The submandibular and sublingual glands are rarely involved by mestastatic disease. Secondary lesions arising from distant primary tumors may occasionally involve the parotid gland, but they are extremely rare in the other major salivary glands. The second reported case of metastatic carcinoma in the submandibular gland is presented here. Our case and the previously reported case are similar in that both primary tumors originated in the breast. The clinical and morphologic features are reviewed.", "contents": "Metastatic malignancy in the submandibular gland. Metastatic disease in the major salivary glands has been observed and reported in the literature. Often the site of origin of the primary tumor is the skin or mucosal lining of the head and neck structures, and the primary tumors most commonly are melanomas or squamous-cell carcinomas. The most frequently involved salivary gland is the parotid. The submandibular and sublingual glands are rarely involved by mestastatic disease. Secondary lesions arising from distant primary tumors may occasionally involve the parotid gland, but they are extremely rare in the other major salivary glands. The second reported case of metastatic carcinoma in the submandibular gland is presented here. Our case and the previously reported case are similar in that both primary tumors originated in the breast. The clinical and morphologic features are reviewed."} {"id": "PMID:163465", "title": "Multiple unit activity study of brain stem and limbic structures during environmental habituation and circadian rhythm.", "content": "Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness.", "contents": "Multiple unit activity study of brain stem and limbic structures during environmental habituation and circadian rhythm. Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness."} {"id": "PMID:163466", "title": "Antagonism between parathyroid hormone and norepinephrine on cyclic adenosine-3':5'-monophosphate (cAMP) levels in isolated tubules from rat kidney cortex.", "content": "Isolated rat kidney cortex tubules were used as a model system to study the hormonal regulation of cyclic adenosine-3':5'-monophosphate (cAMP) levels in vitro. When incubated over 15 min, parathyroid hormone increased cAMP levels 4-fold in the absence of inhibitors of cAMP phosphodiesterase. Norepinephrine in a concentration of 5-10-7 M which had itself no effect on cAMP levels under this condition, inhibited the effect of parathyroid hormone by 50%. This effect of the catecholamines could be completely abolished by the addition of an alpha-receptor blocking agent, phentolamine. The addition of an inhibitor of cAMP phosphodiesterase, in a concentration sufficient to prevent the breakdown of extratubular cAMP, potentiated hormone effects on cAMP levels. The antagonism between catecholamines and parathyroid hormone on cAMP levels was however not abolished by this treatment. This indicated that catecholamines probably inhibited parathyroid hormone stimulated cAMP formation. Since most of the cAMP was found to be intratubular, it can be assumed that norepinephrine and parathyroid hormone interact in the same cell. Proximal tubular sodium reabsorption and renal gluconeogenesis are discussed as possible events of this hormone interaction.", "contents": "Antagonism between parathyroid hormone and norepinephrine on cyclic adenosine-3':5'-monophosphate (cAMP) levels in isolated tubules from rat kidney cortex. Isolated rat kidney cortex tubules were used as a model system to study the hormonal regulation of cyclic adenosine-3':5'-monophosphate (cAMP) levels in vitro. When incubated over 15 min, parathyroid hormone increased cAMP levels 4-fold in the absence of inhibitors of cAMP phosphodiesterase. Norepinephrine in a concentration of 5-10-7 M which had itself no effect on cAMP levels under this condition, inhibited the effect of parathyroid hormone by 50%. This effect of the catecholamines could be completely abolished by the addition of an alpha-receptor blocking agent, phentolamine. The addition of an inhibitor of cAMP phosphodiesterase, in a concentration sufficient to prevent the breakdown of extratubular cAMP, potentiated hormone effects on cAMP levels. The antagonism between catecholamines and parathyroid hormone on cAMP levels was however not abolished by this treatment. This indicated that catecholamines probably inhibited parathyroid hormone stimulated cAMP formation. Since most of the cAMP was found to be intratubular, it can be assumed that norepinephrine and parathyroid hormone interact in the same cell. Proximal tubular sodium reabsorption and renal gluconeogenesis are discussed as possible events of this hormone interaction."} {"id": "PMID:163467", "title": "Adenylate cyclase activity along the rabbit nephron as measured in single isolated segments.", "content": "A method is described, which allows adenylate cyclase activity measurement in single pieces of various nephron segments. Tubular samples of 0.5 to 2 mm length were isolated by microdissection from collagenase treated slices of rabbit kidney. A photograph of each piece was taken in order to measure its length. After a permeabilisation treatment involving preincubation in a hypoosmotic medium and a freezing step, each sample was incubated for 30 mm at 30 degrees C in a medium containing high specific (alpha-32-P)-ATP 3-10-4 M, final volume 2.5 mu 1. The (32P)-cAMP formed was separated from the other labelled nucleotides by filtering the incubate on a dry aluminium oxide microcolumn, 3H cAMP was added as a tracer for measuring cAMP recovery. The sensitivity of the method was found to be a few fentomoles (10-15 M) cAMP. cAMP generation increased linearly as a function of the incubation time up to more than 30 min, and as a function of the length of the segment used. Control and fluoride (5 mM) stimulated adenvlate cyclase activities were measured in the following segments of the nephron: early proximal convoluted tubule (PCT), pars recta of the proximal tubule (PR), thin descending limb of the loop (TDL), cortical portion of the thick ascending limb (CAL), distal convoluted tubule (dct), first branched portion of the collecting tubule (BCT), further cortical (CCT) and medullary (MCT) portions of the collecting tubule. Mean control adenylate cyclase activity varied from 7 (PR) to 75 (BCT) fmoles/mm/30 min. Flouride addition resulted in a 10 (BCT) to 50 (PR) fold increase in enzyme activity. Series of replicates gave a scatter equal to plus or minus 20% (S.D. as a per cent of the mean). The method described appears to be suitable to determine which nephron segments contain hormone-dependent adenylate cyclase.", "contents": "Adenylate cyclase activity along the rabbit nephron as measured in single isolated segments. A method is described, which allows adenylate cyclase activity measurement in single pieces of various nephron segments. Tubular samples of 0.5 to 2 mm length were isolated by microdissection from collagenase treated slices of rabbit kidney. A photograph of each piece was taken in order to measure its length. After a permeabilisation treatment involving preincubation in a hypoosmotic medium and a freezing step, each sample was incubated for 30 mm at 30 degrees C in a medium containing high specific (alpha-32-P)-ATP 3-10-4 M, final volume 2.5 mu 1. The (32P)-cAMP formed was separated from the other labelled nucleotides by filtering the incubate on a dry aluminium oxide microcolumn, 3H cAMP was added as a tracer for measuring cAMP recovery. The sensitivity of the method was found to be a few fentomoles (10-15 M) cAMP. cAMP generation increased linearly as a function of the incubation time up to more than 30 min, and as a function of the length of the segment used. Control and fluoride (5 mM) stimulated adenvlate cyclase activities were measured in the following segments of the nephron: early proximal convoluted tubule (PCT), pars recta of the proximal tubule (PR), thin descending limb of the loop (TDL), cortical portion of the thick ascending limb (CAL), distal convoluted tubule (dct), first branched portion of the collecting tubule (BCT), further cortical (CCT) and medullary (MCT) portions of the collecting tubule. Mean control adenylate cyclase activity varied from 7 (PR) to 75 (BCT) fmoles/mm/30 min. Flouride addition resulted in a 10 (BCT) to 50 (PR) fold increase in enzyme activity. Series of replicates gave a scatter equal to plus or minus 20% (S.D. as a per cent of the mean). The method described appears to be suitable to determine which nephron segments contain hormone-dependent adenylate cyclase."} {"id": "PMID:163468", "title": "PTH sensitive adenyl cyclase activity in different segments of the rabbit nephron.", "content": "PTH sensitive adenylate cyclase activity was measured in 9 different segments of the nephron, isolated by microdissection from collagenase-treated rabbit kidney slices. The enzyme of the following segments was stimulated by PTH, 1 U/ml: PCT. (proximal convoluted tubule); PR (pars recta); CAL (cortical portion of the thick ascending limb); DCT (distal convoluted tubule); BCT (first, branched portion of the collecting tubule); the segments which did not respond to PTH were: TDL (thin descending limb): MAL (medullary portion of the thick ascending limb); CCT (cortical portion of the collecting tubule distally adjacent to BCT); MCT (collecting tubule from the outer medulla). PTH sensitive adenylate cyclase per mm tubule in PR was half that measured in PCT. Half maximal stimulation corresponded to 50-100mm U/ml PTH (1-2 times 10-8M) in both PCT and PR, and to about 350 mm U/ml in CAL. PTH (1 U/ml) stimulation factors ranged from 5 to 60 depending on the structures. It is concluded that in addition to PCT and PR, CAL and BCT might be target structures involved in the physiological actions of PTH on the kidney.", "contents": "PTH sensitive adenyl cyclase activity in different segments of the rabbit nephron. PTH sensitive adenylate cyclase activity was measured in 9 different segments of the nephron, isolated by microdissection from collagenase-treated rabbit kidney slices. The enzyme of the following segments was stimulated by PTH, 1 U/ml: PCT. (proximal convoluted tubule); PR (pars recta); CAL (cortical portion of the thick ascending limb); DCT (distal convoluted tubule); BCT (first, branched portion of the collecting tubule); the segments which did not respond to PTH were: TDL (thin descending limb): MAL (medullary portion of the thick ascending limb); CCT (cortical portion of the collecting tubule distally adjacent to BCT); MCT (collecting tubule from the outer medulla). PTH sensitive adenylate cyclase per mm tubule in PR was half that measured in PCT. Half maximal stimulation corresponded to 50-100mm U/ml PTH (1-2 times 10-8M) in both PCT and PR, and to about 350 mm U/ml in CAL. PTH (1 U/ml) stimulation factors ranged from 5 to 60 depending on the structures. It is concluded that in addition to PCT and PR, CAL and BCT might be target structures involved in the physiological actions of PTH on the kidney."} {"id": "PMID:163470", "title": "[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration].", "content": "The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use.", "contents": "[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration]. The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use."} {"id": "PMID:163471", "title": "The discharge crisis: the experience of families of psychiatric patients.", "content": "Families of 16 psychiatric patients were interviewed immediately prior to discharge regarding the impending discharge of their relative, events prior to admission, and the families' impression of the hospitalization. Despite wide variation sample families' descriptors and differences in exposure to the treatment settings, there was a marked uniformity in responses. The families were not prepared for the discharge of their relative. In spite of their experiences and exposure to treatment, families continued to demonstrate tremendous uncertainty and lack of direction about the future with the patient. Families did not view the patient as ready to be discharged. They had not experienced an opportunity to express their views or participate in decision making. They did not consider the staff as a resource for themselves.", "contents": "The discharge crisis: the experience of families of psychiatric patients. Families of 16 psychiatric patients were interviewed immediately prior to discharge regarding the impending discharge of their relative, events prior to admission, and the families' impression of the hospitalization. Despite wide variation sample families' descriptors and differences in exposure to the treatment settings, there was a marked uniformity in responses. The families were not prepared for the discharge of their relative. In spite of their experiences and exposure to treatment, families continued to demonstrate tremendous uncertainty and lack of direction about the future with the patient. Families did not view the patient as ready to be discharged. They had not experienced an opportunity to express their views or participate in decision making. They did not consider the staff as a resource for themselves."} {"id": "PMID:163479", "title": "Cadmium-its in vivo detection in man.", "content": "Neutron capture gamma-ray analysis has been applied to the in vivo detection of Cd in man. The technique was designed for the screening of industrial workers at risk. The limit of sensitivity in a liver-sized phantom is 0-5 ppm for a dose of 0-4 rad. Reproducibility and the effects of positional uncertainties have been investigated. A number of cadavers were studied to establish normal limits prior to commencement of a programme of clinical investigation. A patient with known Cd poisoning was estimated to contain 65-110 ppm of Cd in his liver. A liver dose of 0-05 rad was required.", "contents": "Cadmium-its in vivo detection in man. Neutron capture gamma-ray analysis has been applied to the in vivo detection of Cd in man. The technique was designed for the screening of industrial workers at risk. The limit of sensitivity in a liver-sized phantom is 0-5 ppm for a dose of 0-4 rad. Reproducibility and the effects of positional uncertainties have been investigated. A number of cadavers were studied to establish normal limits prior to commencement of a programme of clinical investigation. A patient with known Cd poisoning was estimated to contain 65-110 ppm of Cd in his liver. A liver dose of 0-05 rad was required."} {"id": "PMID:163483", "title": "Infectious diseases in primitive societies.", "content": "Incidence of various infectious diseases in several Amazon Indian tribes has been determined serologically. Diseases that infect only man fall into two distinct categories. Those which can persist in an individual for a prolonged period are highly endemic, but those which are infectious only in the acute phase die out quickly after introduction. The suggestion is made that the latter diseases could not perpetuate themselves before the advent of advanced cultures and did not exert selective pressures on the human genetic constitution until relatively recently.", "contents": "Infectious diseases in primitive societies. Incidence of various infectious diseases in several Amazon Indian tribes has been determined serologically. Diseases that infect only man fall into two distinct categories. Those which can persist in an individual for a prolonged period are highly endemic, but those which are infectious only in the acute phase die out quickly after introduction. The suggestion is made that the latter diseases could not perpetuate themselves before the advent of advanced cultures and did not exert selective pressures on the human genetic constitution until relatively recently."} {"id": "PMID:163480", "title": "A comparative study of agar overlay and standard tissue culture methods for isolation of enteroviruses.", "content": "A study was made of the isolation of enteroviruses from 62 cerebrospinal fluids and 141 autopsy specimens with standard fluid monolayer tissue culture methods and tissue cultures under agar overlay with and without added MgCl2 (0.025M). Sixteen virus isolations were made only by the overlay method, two only by the standard technique, and six by both procedures. Additional studies were carried out on 975 diagnostic specimens of various types with standard tissue culture methods and with primary rhesus kidney cells under agar overlay containing 0.025M MgCl2. Seventeen virus isolations were made only by the overlay procedure, 20 only by the standard tissue culture method, and 75 by both techniques. Since there were instances in which either the agar overlay or the standard method alone succeeded in isolating a virus, use of both types of procedures would be desirable to isolate as many enteroviruses as possible from clinical specimens.", "contents": "A comparative study of agar overlay and standard tissue culture methods for isolation of enteroviruses. A study was made of the isolation of enteroviruses from 62 cerebrospinal fluids and 141 autopsy specimens with standard fluid monolayer tissue culture methods and tissue cultures under agar overlay with and without added MgCl2 (0.025M). Sixteen virus isolations were made only by the overlay method, two only by the standard technique, and six by both procedures. Additional studies were carried out on 975 diagnostic specimens of various types with standard tissue culture methods and with primary rhesus kidney cells under agar overlay containing 0.025M MgCl2. Seventeen virus isolations were made only by the overlay procedure, 20 only by the standard tissue culture method, and 75 by both techniques. Since there were instances in which either the agar overlay or the standard method alone succeeded in isolating a virus, use of both types of procedures would be desirable to isolate as many enteroviruses as possible from clinical specimens."} {"id": "PMID:163484", "title": "Sleep and cardiac rhythm in the gray seal.", "content": "Telemetric studies of electroencephalograms, electrocardiograms, and electroculograms and concurrent observations of behavior revealed that seals can sleep underwater, on the surface, or while hauled out. Rapid eye movement preceded slow wave sleep and was accompanied by increased respiratory rate and rhythmic tachycardia. While slow wave sleep occurred under all sleep conditions, rapid eye movement occurred only when a seal was hanging at the water surface or hauled out, never underwater.", "contents": "Sleep and cardiac rhythm in the gray seal. Telemetric studies of electroencephalograms, electrocardiograms, and electroculograms and concurrent observations of behavior revealed that seals can sleep underwater, on the surface, or while hauled out. Rapid eye movement preceded slow wave sleep and was accompanied by increased respiratory rate and rhythmic tachycardia. While slow wave sleep occurred under all sleep conditions, rapid eye movement occurred only when a seal was hanging at the water surface or hauled out, never underwater."} {"id": "PMID:163486", "title": "Ornithine decarboxylase activity: control by cyclic nucleotides.", "content": "Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex. These increases are followed by dramatic increases in ornithine decarboxylase activity is due to new enzyme systhesis. The data suggest that the decarboxylase activity is regulated by an increase in cyclic AMP.", "contents": "Ornithine decarboxylase activity: control by cyclic nucleotides. Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex. These increases are followed by dramatic increases in ornithine decarboxylase activity is due to new enzyme systhesis. The data suggest that the decarboxylase activity is regulated by an increase in cyclic AMP."} {"id": "PMID:163487", "title": "Selection of a variant lymphoma cell deficient in adenylate cyclase.", "content": "Isoproterenol, a stimulator of adenylate cyclase, was used to select a stable variant clone of mouse lymphosarcoma cells deficient in the enzyme. The inability of four different stimulators to activate cyclic adenosine monophosphate synthesis in the variant, in contrast to its wild-type parent, implies that in normal cells one type of adenylate cyclase molecular can respond to different activators.", "contents": "Selection of a variant lymphoma cell deficient in adenylate cyclase. Isoproterenol, a stimulator of adenylate cyclase, was used to select a stable variant clone of mouse lymphosarcoma cells deficient in the enzyme. The inability of four different stimulators to activate cyclic adenosine monophosphate synthesis in the variant, in contrast to its wild-type parent, implies that in normal cells one type of adenylate cyclase molecular can respond to different activators."} {"id": "PMID:163488", "title": "Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex.", "content": "Electrophysiologically identified pyramidal tract neurons in the rat cerebral cortex were tested with norepinephrine, acetylcholine, adenosine 3',5'-monophosphate (cyclic AMP), and guanosine 3',5'-monophosphate (cyclic GMP) applied by microiontophoresis. The neurons were usually inhibited by norepinephrine and cyclic AMP, but excited by acetylcholine and cyclic GMP. These opposing responses of pyramidal tract neurons to cyclic AMP and cyclic GMP suggests that these two nucleotides could function as reciprocal intracellular second messengers for norepinephrine and acetylcholine, respectively.", "contents": "Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex. Electrophysiologically identified pyramidal tract neurons in the rat cerebral cortex were tested with norepinephrine, acetylcholine, adenosine 3',5'-monophosphate (cyclic AMP), and guanosine 3',5'-monophosphate (cyclic GMP) applied by microiontophoresis. The neurons were usually inhibited by norepinephrine and cyclic AMP, but excited by acetylcholine and cyclic GMP. These opposing responses of pyramidal tract neurons to cyclic AMP and cyclic GMP suggests that these two nucleotides could function as reciprocal intracellular second messengers for norepinephrine and acetylcholine, respectively."} {"id": "PMID:163489", "title": "Primate type C virus p30 antigen in cells from humans with acute leukemia.", "content": "Antigens related to the major structural protein (p30) of type C viruses isolated from a woolly monkey and a gibbon ape were found in peripheral white blood cells from five patients with acute leukemia.", "contents": "Primate type C virus p30 antigen in cells from humans with acute leukemia. Antigens related to the major structural protein (p30) of type C viruses isolated from a woolly monkey and a gibbon ape were found in peripheral white blood cells from five patients with acute leukemia."} {"id": "PMID:163491", "title": "Phosphorylation of lymphocyte nuclear acidic proteins: regulation by cyclic nucleotides.", "content": "Guanosine 3',5'-monophosphate (cyclic GMP) and cholinergic agents stimulate incorporation of phosphate into specific nuclear acidic proteins of horse peripheral blood lymphocytes. Agents that raise intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibit nuclear acidic protein phosphorylation. The opposing effects of cyclic GMP and cyclic AMP upon nuclear protein phosphorylation parallel the effects of the cyclic nucleotides upon induction of lymphocyte proliferation.", "contents": "Phosphorylation of lymphocyte nuclear acidic proteins: regulation by cyclic nucleotides. Guanosine 3',5'-monophosphate (cyclic GMP) and cholinergic agents stimulate incorporation of phosphate into specific nuclear acidic proteins of horse peripheral blood lymphocytes. Agents that raise intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibit nuclear acidic protein phosphorylation. The opposing effects of cyclic GMP and cyclic AMP upon nuclear protein phosphorylation parallel the effects of the cyclic nucleotides upon induction of lymphocyte proliferation."} {"id": "PMID:163492", "title": "Insulin-induced augmentation of lymphocyte-mediated cytotoxicity.", "content": "Physiologic concentrations of insulin enhance the ability of cytotoxic lymphocytes to injure target cells. The effect of insulin closely resembles the action of cholinomimetics and guanosine 3',5'-monophosphate upon this system. Since both insulin and cholinomimetics elevate intracellular concentrations of guanosine 3',5'-monophosphate, a common mode of action is suggested.", "contents": "Insulin-induced augmentation of lymphocyte-mediated cytotoxicity. Physiologic concentrations of insulin enhance the ability of cytotoxic lymphocytes to injure target cells. The effect of insulin closely resembles the action of cholinomimetics and guanosine 3',5'-monophosphate upon this system. Since both insulin and cholinomimetics elevate intracellular concentrations of guanosine 3',5'-monophosphate, a common mode of action is suggested."} {"id": "PMID:163493", "title": "Prolactin receptors in rat liver: possible induction by prolactin.", "content": "A prolactin receptor, present in adult female rat liver, can be induced in males by estrogen. Hypophysectomy diminished receptor levels in the female and rendered males unresponsive to estrogen. A renal pituitary implant blunted the decrease in hypophysectomized females and induced the receptor in hyophysectomized males. The increased receptor level in hypophysectomized males with a renal pituitary implant was preceded by a sustained elevation of circulating prolactin. Our observations suggest that prolactin induces its own receptor.", "contents": "Prolactin receptors in rat liver: possible induction by prolactin. A prolactin receptor, present in adult female rat liver, can be induced in males by estrogen. Hypophysectomy diminished receptor levels in the female and rendered males unresponsive to estrogen. A renal pituitary implant blunted the decrease in hypophysectomized females and induced the receptor in hyophysectomized males. The increased receptor level in hypophysectomized males with a renal pituitary implant was preceded by a sustained elevation of circulating prolactin. Our observations suggest that prolactin induces its own receptor."} {"id": "PMID:163494", "title": "Butylated hydroxytoluene inactivated lipid-containing viruses.", "content": "Butylated hydroxytoluene (BHT) is widely used as a food preservative for its antioxidizing property. This small, hydrophobic molecule has been found to be a potent inactivator of lipid-containing mammalian and bacterial viruses.", "contents": "Butylated hydroxytoluene inactivated lipid-containing viruses. Butylated hydroxytoluene (BHT) is widely used as a food preservative for its antioxidizing property. This small, hydrophobic molecule has been found to be a potent inactivator of lipid-containing mammalian and bacterial viruses."} {"id": "PMID:163495", "title": "Electron spin resonance for detecting polyadenylate tracts in RNA's.", "content": "Electron spin resonance is used to detect RNA's that contain polyadenylate tracts. The method depends on the ability of RNA's that contain polyadenylate sequences to associate with poly(2'-deoxy-2'-fluoro)uridylic acid, which has been spin-labeled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl. The formation of the hybridization product can be detected by monitoring the decrease in mobility of the spin probe.", "contents": "Electron spin resonance for detecting polyadenylate tracts in RNA's. Electron spin resonance is used to detect RNA's that contain polyadenylate tracts. The method depends on the ability of RNA's that contain polyadenylate sequences to associate with poly(2'-deoxy-2'-fluoro)uridylic acid, which has been spin-labeled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl. The formation of the hybridization product can be detected by monitoring the decrease in mobility of the spin probe."} {"id": "PMID:163496", "title": "Formation of the enzymatic apparatus of respiration in growing cells. Communication II. Reorganization of the respiratory cycle of mitochondria in the corn root tip.", "content": "The content of cytochromes a,b and c, the activity of marker enzymes of the matrix and inner membrane of the mitochondria: glutamate dehydrogenase and cytochrome oxidase, as well as the rate of absorption of O2 by root segments in the presence of respiratory substrates, oxygen, inhibitors of respiration, and dinitrophenol, were determined. The intensification of cell respiration in the phase of elongation is determined not so much by new formation of cytochrome components of the respiratory cycle (during this period there is an accumulation only of cytochrome c) as by reorganization of the respiratory cycle (primarily its portion NADH - cytochrome b) and synthesis of enzymes of the matrix.", "contents": "Formation of the enzymatic apparatus of respiration in growing cells. Communication II. Reorganization of the respiratory cycle of mitochondria in the corn root tip. The content of cytochromes a,b and c, the activity of marker enzymes of the matrix and inner membrane of the mitochondria: glutamate dehydrogenase and cytochrome oxidase, as well as the rate of absorption of O2 by root segments in the presence of respiratory substrates, oxygen, inhibitors of respiration, and dinitrophenol, were determined. The intensification of cell respiration in the phase of elongation is determined not so much by new formation of cytochrome components of the respiratory cycle (during this period there is an accumulation only of cytochrome c) as by reorganization of the respiratory cycle (primarily its portion NADH - cytochrome b) and synthesis of enzymes of the matrix."} {"id": "PMID:163497", "title": "Investigation of oogenesis in hydra. Communication I. Ultrastructure of interstitial cells at early stages of their transformation into oocytes.", "content": "We studied ultrastructure of the interstitial cells (i-cells) at successive stages of their transformation into oocytes. The i-cells that form the epidermal thickening in the genital zone of the animal start to proliferate in hydras approaching sexual reproduction. Undifferentiated i-cells are characterized by a high density of diffusely disposed ribosomes and almost total absence of membranous structures. Femal sex cells starting to undergo differentiation are characterized by the appearance of aggregations of finely filamentous material in the cytoplasm. This material is of nuclear origin and is often surrounded by mitochondria. Dimensions of the i-cells increase rapidly, and single elongated cisterns of the granular endoplasmic reticulum appear in them. These cisterns run parallel to the cell surface and give rise to minute smooth-surfaced vesicles, whose membranes fuse wtih the cytoplasmic membrane in such a way that their contents are emptied into the intercellular space. Different sectors of the cell are marked by the appearance of grouped cisterns of the granular endoplasmic reticulum. Such cisterns give rise to smooth-surfaced vesicles, which form numerous Golgi complexes. The number of mitochondria increases simultaneously; aggregations of lipid drops with glycogen granules among them start to appear; and escape of nuclear material into the cytplasm intensifies. Such cells at the stage of cytoplasmic growth and accumulation of organelles and yolk inclusions. In connection with this, it is suggested that the term \"oogonium\" (which is used to designate such cells in the literature) be retained only for proliferating i-cells containing finely filamentous nuclear material in the cytoplasm in the genital zone of the hydra.", "contents": "Investigation of oogenesis in hydra. Communication I. Ultrastructure of interstitial cells at early stages of their transformation into oocytes. We studied ultrastructure of the interstitial cells (i-cells) at successive stages of their transformation into oocytes. The i-cells that form the epidermal thickening in the genital zone of the animal start to proliferate in hydras approaching sexual reproduction. Undifferentiated i-cells are characterized by a high density of diffusely disposed ribosomes and almost total absence of membranous structures. Femal sex cells starting to undergo differentiation are characterized by the appearance of aggregations of finely filamentous material in the cytoplasm. This material is of nuclear origin and is often surrounded by mitochondria. Dimensions of the i-cells increase rapidly, and single elongated cisterns of the granular endoplasmic reticulum appear in them. These cisterns run parallel to the cell surface and give rise to minute smooth-surfaced vesicles, whose membranes fuse wtih the cytoplasmic membrane in such a way that their contents are emptied into the intercellular space. Different sectors of the cell are marked by the appearance of grouped cisterns of the granular endoplasmic reticulum. Such cisterns give rise to smooth-surfaced vesicles, which form numerous Golgi complexes. The number of mitochondria increases simultaneously; aggregations of lipid drops with glycogen granules among them start to appear; and escape of nuclear material into the cytplasm intensifies. Such cells at the stage of cytoplasmic growth and accumulation of organelles and yolk inclusions. In connection with this, it is suggested that the term \"oogonium\" (which is used to designate such cells in the literature) be retained only for proliferating i-cells containing finely filamentous nuclear material in the cytoplasm in the genital zone of the hydra."} {"id": "PMID:163501", "title": "Mesothelial reaction of asbestos and other irritants after intraperitoneal injection.", "content": "Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.", "contents": "Mesothelial reaction of asbestos and other irritants after intraperitoneal injection. Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium."} {"id": "PMID:163502", "title": "Technique and results of endoscopic retrograde pancreaticocholangiography. A preliminary report on 140 patients.", "content": "Endoscopic retrograde pancreaticocholangiography (ERPC) has been performed in 140 patients, mainly Blacks and Indians. The first 100 patients have been analysed. The greatest diagnostic yield in this series is in (suspected) obstructive jaundice, where 26 diagnoses were made in 35 patients. In 40 patients with pancreatitis, the widest ducts were seen in 12 patients with calcific pancreatitis, but the procedure was of less help than expected. This was because no patients with continual pain after cessation of alcohol intake were found with operable strictures of the main pancreatic duct. The pancreatic function test with secretin and cholecystokinin-pancreozymin correctly diagnosed 4 patients with non-calcific pancreatitis in whom the ERPC was normal. There was a useful diagnostic yield in patients with unexplained upper gastrointestinal symptoms (15 diagnoses were made in 23 patients).", "contents": "Technique and results of endoscopic retrograde pancreaticocholangiography. A preliminary report on 140 patients. Endoscopic retrograde pancreaticocholangiography (ERPC) has been performed in 140 patients, mainly Blacks and Indians. The first 100 patients have been analysed. The greatest diagnostic yield in this series is in (suspected) obstructive jaundice, where 26 diagnoses were made in 35 patients. In 40 patients with pancreatitis, the widest ducts were seen in 12 patients with calcific pancreatitis, but the procedure was of less help than expected. This was because no patients with continual pain after cessation of alcohol intake were found with operable strictures of the main pancreatic duct. The pancreatic function test with secretin and cholecystokinin-pancreozymin correctly diagnosed 4 patients with non-calcific pancreatitis in whom the ERPC was normal. There was a useful diagnostic yield in patients with unexplained upper gastrointestinal symptoms (15 diagnoses were made in 23 patients)."} {"id": "PMID:163503", "title": "The inhibition of c-AMP-phosphodiesterase by phenobarbitone.", "content": "The early effects of phenobarbitone, theophylline, thyroxine and of combinations of these drugs, on rat liver microsomal aniline hydroxylase activity, were studied, and the results were compared with the effect of phenobarbitone on purified c-AMP-phosphodiesterase in vitro. The stimulatory effect of phenobarbitone on hepatic microsomal aniline hydroxylase activity was found to be simulated by theophylline, and also by thyroxine. When phenobarbitone and thyroxine were used, the effect was approximately equal to the sum of the individual effects, but no summation was seen when phenobarbitone and theophylline were used. Phenobarbitone caused an inhibition of c-AMP-phosphodiesterase activity in vitro. The magnitude of this inhibitory effect was found to be dependent on the dose of phenobarbitone. The significance of c-AMP-phosphodiesterase inhibition by phenobarbitone is discussed.", "contents": "The inhibition of c-AMP-phosphodiesterase by phenobarbitone. The early effects of phenobarbitone, theophylline, thyroxine and of combinations of these drugs, on rat liver microsomal aniline hydroxylase activity, were studied, and the results were compared with the effect of phenobarbitone on purified c-AMP-phosphodiesterase in vitro. The stimulatory effect of phenobarbitone on hepatic microsomal aniline hydroxylase activity was found to be simulated by theophylline, and also by thyroxine. When phenobarbitone and thyroxine were used, the effect was approximately equal to the sum of the individual effects, but no summation was seen when phenobarbitone and theophylline were used. Phenobarbitone caused an inhibition of c-AMP-phosphodiesterase activity in vitro. The magnitude of this inhibitory effect was found to be dependent on the dose of phenobarbitone. The significance of c-AMP-phosphodiesterase inhibition by phenobarbitone is discussed."} {"id": "PMID:163509", "title": "Ultrasound in diagnosis of congenital hydronephrosis due to obstruction of pelviureteric junction.", "content": "The use of ultrasonography in the diagnosis of upper abdominal masses with nonfunctioning kidneys is described. Two cases of congential hydronephrosis due to obstruction of the pelviuretic junction are presented, both of which were diagnosed by B-scan ultrasound examination. Diagnostic ultrasound is a simple, noninvasive and reliable method of differentiating cystic from solid lesions and of assessing whether or not a mass is renal or extrarenal. It is recommended that all patients seen with an upper abdominal mass and/or nonfunctioning kidney be examined by ultrasound.", "contents": "Ultrasound in diagnosis of congenital hydronephrosis due to obstruction of pelviureteric junction. The use of ultrasonography in the diagnosis of upper abdominal masses with nonfunctioning kidneys is described. Two cases of congential hydronephrosis due to obstruction of the pelviuretic junction are presented, both of which were diagnosed by B-scan ultrasound examination. Diagnostic ultrasound is a simple, noninvasive and reliable method of differentiating cystic from solid lesions and of assessing whether or not a mass is renal or extrarenal. It is recommended that all patients seen with an upper abdominal mass and/or nonfunctioning kidney be examined by ultrasound."} {"id": "PMID:163515", "title": "Feline leukaemia virus and its clinical effects in cats.", "content": "Feline leukemia virus (FeLV) infection is common among cats where contact is high. The virus can be transmitted readily between cats. It causes a variety of haemopoietic and lymphoid neoplasms; the most common types are alimentary, multicentric and thymic lymphosarcoma and lymphatic leukaemia. The virus is involved in the aetiology of certain other diseases including anaemia, glomerulonephritis and an immunosuppressive syndrome which predisposes cats to intercurrent infections. Many infected cats mount an immune response and do not suffer from any of these. The immune status is shown by serum antibody levels to feline leukaemia virus associated cell membrane antigens. Cats with a titre of 32 or more are most unlikely to suffer any ill effects and may eliminate the virus infection. The outcome of infection in an individual cat depends on the immunological competence of the cat, the dose of virus received and its ability to induce immunosuppression. FeLV infection can be detected by examination of tissues by electron microscopy, and by culture of virus from plasma and other tissues. In the United States, a method is now in use for the detection of leukaemia virus antigen in peripheral blood leukocytes; this is carried out on ordinary blood films. Successful prototype vaccines have been developed against FeLV. This paper describes the natural history of the virus, the diseases in which it is implicated and discusses recently developed diagnostic methods.", "contents": "Feline leukaemia virus and its clinical effects in cats. Feline leukemia virus (FeLV) infection is common among cats where contact is high. The virus can be transmitted readily between cats. It causes a variety of haemopoietic and lymphoid neoplasms; the most common types are alimentary, multicentric and thymic lymphosarcoma and lymphatic leukaemia. The virus is involved in the aetiology of certain other diseases including anaemia, glomerulonephritis and an immunosuppressive syndrome which predisposes cats to intercurrent infections. Many infected cats mount an immune response and do not suffer from any of these. The immune status is shown by serum antibody levels to feline leukaemia virus associated cell membrane antigens. Cats with a titre of 32 or more are most unlikely to suffer any ill effects and may eliminate the virus infection. The outcome of infection in an individual cat depends on the immunological competence of the cat, the dose of virus received and its ability to induce immunosuppression. FeLV infection can be detected by examination of tissues by electron microscopy, and by culture of virus from plasma and other tissues. In the United States, a method is now in use for the detection of leukaemia virus antigen in peripheral blood leukocytes; this is carried out on ordinary blood films. Successful prototype vaccines have been developed against FeLV. This paper describes the natural history of the virus, the diseases in which it is implicated and discusses recently developed diagnostic methods."} {"id": "PMID:163516", "title": "Equine infectious respiratory disease.", "content": "During the past 20 years the equine population of Great Britain and Ireland has increased with the result that the practising veterinary surgeon is more frequently called upon to advise on equine problems. A significant portion of this advice is concerned with the examination of horses showing signs of this advice is concerned with the examination of horses showing signs of respiratory disease. Numerous pathogens, which include viruses, bacteria, parasites and moulds invade the respiratory tract causing similar signs of illness. It is therefore difficult to provide an aetiological diagnosis based on a clinical examination. Field studies supported by laboratory investigations have established that influenza and herpes viruses are frequently responsible for outbreaks of disease. Epidemiological studies suggest that other factors including the immune state of the equine population influence the distribution and severity of respiratory disease. The aetiology, diagnosis, treatment and control of equine infectious respiratory disease are discussed below.", "contents": "Equine infectious respiratory disease. During the past 20 years the equine population of Great Britain and Ireland has increased with the result that the practising veterinary surgeon is more frequently called upon to advise on equine problems. A significant portion of this advice is concerned with the examination of horses showing signs of this advice is concerned with the examination of horses showing signs of respiratory disease. Numerous pathogens, which include viruses, bacteria, parasites and moulds invade the respiratory tract causing similar signs of illness. It is therefore difficult to provide an aetiological diagnosis based on a clinical examination. Field studies supported by laboratory investigations have established that influenza and herpes viruses are frequently responsible for outbreaks of disease. Epidemiological studies suggest that other factors including the immune state of the equine population influence the distribution and severity of respiratory disease. The aetiology, diagnosis, treatment and control of equine infectious respiratory disease are discussed below."} {"id": "PMID:163517", "title": "Viral enteritis of calves.", "content": "Calf diarrhoea is an important cause of economic loss. The aetiology of the disease is considered with particular reference to the role of viruses. Although many microbial organisms have been associated with the disease, there is doubt concerning their true role as causative agents. Two viruses, neonatal calf diarrhoea reovirus-life agent and calf coronavirus, have been discovered recently which appear to play an important role in many cases of diarrhoea and the evidence for considering them to be primary causes of the disease is discussed.", "contents": "Viral enteritis of calves. Calf diarrhoea is an important cause of economic loss. The aetiology of the disease is considered with particular reference to the role of viruses. Although many microbial organisms have been associated with the disease, there is doubt concerning their true role as causative agents. Two viruses, neonatal calf diarrhoea reovirus-life agent and calf coronavirus, have been discovered recently which appear to play an important role in many cases of diarrhoea and the evidence for considering them to be primary causes of the disease is discussed."} {"id": "PMID:163518", "title": "Bedding materials for cubicles.", "content": "With the shortage of straw, its increasing cost, its handling and storage, farmers are seeking suitable alternative bedding materials for cubicles.", "contents": "Bedding materials for cubicles. With the shortage of straw, its increasing cost, its handling and storage, farmers are seeking suitable alternative bedding materials for cubicles."} {"id": "PMID:163523", "title": "Mixed M\u00fcllerian tumors of the uterus. Ultrastructural studies on the differentiation of rhabdomyoblasts.", "content": "In the present study the differentiation of rhabdomyoblasts of two carcinosarcomas of the uterus is analysed electronmicroscopically. During the development of rhabdomyoblasts three cell types can be distinguished: 1. the undifferentiated mesenchymal cell with abundant ribosomes but few other cell organelles. Usually these cells are already associated to each other in strands of 2-4 cells. Occasionally cytoplasmic areas with numerous nonspecific filaments can be observed. 2. the light rhabdomyoblast which is characterized by its conspicuous nonspecific cytoplasmic filaments and its reduction in ribosomes. Specific myofilaments can be visualized only occasionally in this cell type. 3. more differentiated rhabdomyoblasts. These cells can be identified clearly by the presence of large numbers of myofibrils and myofibrillar fragments. Higly organized myofibrils as seen in skeletal muscle are seldom found. Transitional forms between these cell types are also observed. The functions of Z-bodies and of the sarcotubular system in the process of myofibrillar differentiation are discussed.", "contents": "Mixed M\u00fcllerian tumors of the uterus. Ultrastructural studies on the differentiation of rhabdomyoblasts. In the present study the differentiation of rhabdomyoblasts of two carcinosarcomas of the uterus is analysed electronmicroscopically. During the development of rhabdomyoblasts three cell types can be distinguished: 1. the undifferentiated mesenchymal cell with abundant ribosomes but few other cell organelles. Usually these cells are already associated to each other in strands of 2-4 cells. Occasionally cytoplasmic areas with numerous nonspecific filaments can be observed. 2. the light rhabdomyoblast which is characterized by its conspicuous nonspecific cytoplasmic filaments and its reduction in ribosomes. Specific myofilaments can be visualized only occasionally in this cell type. 3. more differentiated rhabdomyoblasts. These cells can be identified clearly by the presence of large numbers of myofibrils and myofibrillar fragments. Higly organized myofibrils as seen in skeletal muscle are seldom found. Transitional forms between these cell types are also observed. The functions of Z-bodies and of the sarcotubular system in the process of myofibrillar differentiation are discussed."} {"id": "PMID:163558", "title": "The development of the primitive epithelium and true tegument in the cercaria of Schistosoma mansoni.", "content": "The formation of the final cercarial tegument of Schistosoma mansoni is preceded by that of a so-called primitive epithelium. The primitive epithelium is derived from the tegument of the daughter sporocyst. The final cercarial tegument is formed from peripherally located somatic cells of the cercarial embryo, which expand and coalesce beneath the primitive epithelium. The primitive epithelium degenerates and disappears. The ultrastructure of both epithelia in the course of the development of the cercaria is described in detail. Possible functions are discussed.", "contents": "The development of the primitive epithelium and true tegument in the cercaria of Schistosoma mansoni. The formation of the final cercarial tegument of Schistosoma mansoni is preceded by that of a so-called primitive epithelium. The primitive epithelium is derived from the tegument of the daughter sporocyst. The final cercarial tegument is formed from peripherally located somatic cells of the cercarial embryo, which expand and coalesce beneath the primitive epithelium. The primitive epithelium degenerates and disappears. The ultrastructure of both epithelia in the course of the development of the cercaria is described in detail. Possible functions are discussed."} {"id": "PMID:163560", "title": "Serum growth hormone and gonadotrophins and urinary steroids in adolescent girls.", "content": "In a series of 146 school girls and nurses in the serum levels of growth hormone (GH), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were determined in the afternoon after 4-5 hours' fast. Blood specimens of the menstruating girls were taken on the 7th to 10th day from the beginning of the preceding menstrual bleeding. From the 24-hour urines collected on the previous day the excretion of total oestrogens, 17-ketosteroids and 17-hydrocorticosteroids was determined. The series was grouped according to skeletal age which varied from 8.0 years to the adult stage. In the girls aged 11-13 years the GH curve showed a significant rise parallel with the mean height curve. The FSH values at the early age of 8-9 years corresponded to the follicular phase of adult women. The LH level increased syteeply up to the 15th year of bone age and mean values of adults were found to be about three times those of childhood. The excretion of total oestrogens and 17-ketosteroids increased steadily up to the full maturity of skeletal age. In the oldest group of girls the excretion was about four times that of the group aged 8-9 years. The hormonal maturation seems to continue until late puberty. The 17-OHCS, on the other hand, reached the adult level in the group with a bone age of 13 years. The excretion of 17-OHCS shows a steep rise from the age of 11 to 12 years and this acceleration of excretion perhaps exceeds the increase in surface area.", "contents": "Serum growth hormone and gonadotrophins and urinary steroids in adolescent girls. In a series of 146 school girls and nurses in the serum levels of growth hormone (GH), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were determined in the afternoon after 4-5 hours' fast. Blood specimens of the menstruating girls were taken on the 7th to 10th day from the beginning of the preceding menstrual bleeding. From the 24-hour urines collected on the previous day the excretion of total oestrogens, 17-ketosteroids and 17-hydrocorticosteroids was determined. The series was grouped according to skeletal age which varied from 8.0 years to the adult stage. In the girls aged 11-13 years the GH curve showed a significant rise parallel with the mean height curve. The FSH values at the early age of 8-9 years corresponded to the follicular phase of adult women. The LH level increased syteeply up to the 15th year of bone age and mean values of adults were found to be about three times those of childhood. The excretion of total oestrogens and 17-ketosteroids increased steadily up to the full maturity of skeletal age. In the oldest group of girls the excretion was about four times that of the group aged 8-9 years. The hormonal maturation seems to continue until late puberty. The 17-OHCS, on the other hand, reached the adult level in the group with a bone age of 13 years. The excretion of 17-OHCS shows a steep rise from the age of 11 to 12 years and this acceleration of excretion perhaps exceeds the increase in surface area."} {"id": "PMID:163561", "title": "Studies on isolated rat adrenal cells. I. Continuous flow and batch incubation.", "content": "A procedure for the continuous flow incubation of isolated adrenal cells is described. In this way the advantages of continuous flow incubations of adrenal tissue are combined with those of isolated adrenal cells. Suspensions of isolated adrenal cells were prepared by a modification of the collagenase method. A sigmoid dose-response curve was obtained when these cells were incubated with ACTH in batch incubations. Under these conditions (in the presence of 1 mU ACTH/ml) the corticosterone production rate remained constant during at least 240 min. This production rate was linearly related to the number of cells. Pre-incubation of the cells during 3 h resulted in an increased response to ACTH. In continuous flow incubations without ACTH the corticosterone production was negligible. With 100 mu U ACTH/ml corticosterone production increased sharply after a short lag period. A maximum was reached after 60-75 min followed by a slow decrease. Cells pre-incubated in the continuous flow apparatus had a slightly diminished ACTH response without loss of affinity to ACTH. The continuous flow incubation of isolated adrenal cells offers new possibilities for the dynamic study of steroid biosynthesis in vitro. The method may also be valuable to study processes in a wide variety of other tissues.", "contents": "Studies on isolated rat adrenal cells. I. Continuous flow and batch incubation. A procedure for the continuous flow incubation of isolated adrenal cells is described. In this way the advantages of continuous flow incubations of adrenal tissue are combined with those of isolated adrenal cells. Suspensions of isolated adrenal cells were prepared by a modification of the collagenase method. A sigmoid dose-response curve was obtained when these cells were incubated with ACTH in batch incubations. Under these conditions (in the presence of 1 mU ACTH/ml) the corticosterone production rate remained constant during at least 240 min. This production rate was linearly related to the number of cells. Pre-incubation of the cells during 3 h resulted in an increased response to ACTH. In continuous flow incubations without ACTH the corticosterone production was negligible. With 100 mu U ACTH/ml corticosterone production increased sharply after a short lag period. A maximum was reached after 60-75 min followed by a slow decrease. Cells pre-incubated in the continuous flow apparatus had a slightly diminished ACTH response without loss of affinity to ACTH. The continuous flow incubation of isolated adrenal cells offers new possibilities for the dynamic study of steroid biosynthesis in vitro. The method may also be valuable to study processes in a wide variety of other tissues."} {"id": "PMID:163562", "title": "Affinity and specificity of antisera against human FSH and TSH obtained by immunizing rabbits with highly purified hormone preparations.", "content": "Two groups of 4 rabbits were immunized according to the method described by Vaitukaitis et al. (1971). One group was given 55 mu g (900 IU) FSH/animal and the other 100 mu g (o.5 IU) TSH/animal. Two highly specific antisera against FSH and one specific antiserum against TSH were obtained. The FSH antisera showed affinities towards LH and TSH of 0.13 and 0.25% respectively as compared to that of FSH. The TSH antisera showed affinities towards LH and FSH of 2.2 and 1.7% respectively as compared to that of TSH. The specific antisera showed no or minor affinities towards the LH-alpha subunit and they were sufficient specific to be used in the radioimmunoassay of serum from pregnant women without pre-absorption with HCG. Scatchard plots showed the association constants of the FSH antisera to be 1.3 times 10-11 and 1.2 times 10-11 1/mol respectively, and the association constant of the TSH antiserum to be 6 times 10-10 1/mol. All 3 antisera showed high titers.", "contents": "Affinity and specificity of antisera against human FSH and TSH obtained by immunizing rabbits with highly purified hormone preparations. Two groups of 4 rabbits were immunized according to the method described by Vaitukaitis et al. (1971). One group was given 55 mu g (900 IU) FSH/animal and the other 100 mu g (o.5 IU) TSH/animal. Two highly specific antisera against FSH and one specific antiserum against TSH were obtained. The FSH antisera showed affinities towards LH and TSH of 0.13 and 0.25% respectively as compared to that of FSH. The TSH antisera showed affinities towards LH and FSH of 2.2 and 1.7% respectively as compared to that of TSH. The specific antisera showed no or minor affinities towards the LH-alpha subunit and they were sufficient specific to be used in the radioimmunoassay of serum from pregnant women without pre-absorption with HCG. Scatchard plots showed the association constants of the FSH antisera to be 1.3 times 10-11 and 1.2 times 10-11 1/mol respectively, and the association constant of the TSH antiserum to be 6 times 10-10 1/mol. All 3 antisera showed high titers."} {"id": "PMID:163559", "title": "The cytopathology of metastatic breast cancer.", "content": "A comparison was made between the histopathologic and cytopathologic appearances of 45 cases of metastatic breast cancer and the histopathologic appearance of their primary neoplasms. Metastatic infiltrating duct carcinoma in body cavity fluids presented with an admixture of single cells and tissue fragments in a ratio of 0.86 to 1. The most commonly occurring tissue fragments were well circumscribed round to oval masses of cells, true acini and cells in tandem arrangement. The cells of metastatic infiltrating duct carcinoma were very pleomorphic ranging from 11.5 to 22 micrometers in diameter. Metastatic infiltrating lobular carcinoma in body cavity fluids presented as a population of primarily single cells with a ratio of 13 single cells to each tissue fragment. The rare tissue fragment encountered was a group loosely cohesive cells without nuclear molding by the cytoplasm of adjacent cells. The individual cells had extremely high nuclear/cellular ratios and were uniform in size ranging in diameter from 10.5 to 14 micrometers. The presentation of metastatic infiltrating lobular carcinoma was very similar to that of lymphomas in body cavity fluids and cerebrospinal fluids and may pose a problem in differential diagnosis.", "contents": "The cytopathology of metastatic breast cancer. A comparison was made between the histopathologic and cytopathologic appearances of 45 cases of metastatic breast cancer and the histopathologic appearance of their primary neoplasms. Metastatic infiltrating duct carcinoma in body cavity fluids presented with an admixture of single cells and tissue fragments in a ratio of 0.86 to 1. The most commonly occurring tissue fragments were well circumscribed round to oval masses of cells, true acini and cells in tandem arrangement. The cells of metastatic infiltrating duct carcinoma were very pleomorphic ranging from 11.5 to 22 micrometers in diameter. Metastatic infiltrating lobular carcinoma in body cavity fluids presented as a population of primarily single cells with a ratio of 13 single cells to each tissue fragment. The rare tissue fragment encountered was a group loosely cohesive cells without nuclear molding by the cytoplasm of adjacent cells. The individual cells had extremely high nuclear/cellular ratios and were uniform in size ranging in diameter from 10.5 to 14 micrometers. The presentation of metastatic infiltrating lobular carcinoma was very similar to that of lymphomas in body cavity fluids and cerebrospinal fluids and may pose a problem in differential diagnosis."} {"id": "PMID:163563", "title": "Accumulation of cyclic AMP in hypothyroidism. Decreased sensitivity to norepinephrine in rat adipocytes.", "content": "The effect of hypothyroidism on the noradrenaline-induced accumulation of 3H-cyclic-AMP was measured in rat epididymal adipose tissue. Adipocytes from hypothyroid animals showed a decreased response to noradrenaline 0.02-0.2 times 10-5 m, while higher concentrations of the catecholamine seemed to elicit the same response in cells obtained from euthyroid or hypothyroid animals. The diminished sensitivity to noradrenaline was unaltered after the addition of phentolamine. It is suggested that thyroid hormones modulate the catecholamine-induced lipolytic response at least partly through the adenyl cyclase cyclic-AMP system.", "contents": "Accumulation of cyclic AMP in hypothyroidism. Decreased sensitivity to norepinephrine in rat adipocytes. The effect of hypothyroidism on the noradrenaline-induced accumulation of 3H-cyclic-AMP was measured in rat epididymal adipose tissue. Adipocytes from hypothyroid animals showed a decreased response to noradrenaline 0.02-0.2 times 10-5 m, while higher concentrations of the catecholamine seemed to elicit the same response in cells obtained from euthyroid or hypothyroid animals. The diminished sensitivity to noradrenaline was unaltered after the addition of phentolamine. It is suggested that thyroid hormones modulate the catecholamine-induced lipolytic response at least partly through the adenyl cyclase cyclic-AMP system."} {"id": "PMID:163564", "title": "Seasonal patterns of sleep stages and secretion of cortisol and growth hormone during 24 hour periods in northern Norway.", "content": "A group of 7 healthy male subjects was studied in regard to sleep stages and 24 h plasma cortisol and growth hormone patterns during the 4 seasons of the year in an Arctic environment (Troms\u00f8, Norway). No difference in total sleep or sleep stage per cents was found for any of the yearly seasons. A small but statistical significant increase in mean plasma cortisol concentration and amount secreted for 24 h was found for the autumn-winter seasons, as compared with the spring and summer. However, no difference in the circadian curve of cortisol hormonal pattern was found. All subjects secreted growth hormone shortly after sleep onset at night and no difference was found as a function of season of the year.", "contents": "Seasonal patterns of sleep stages and secretion of cortisol and growth hormone during 24 hour periods in northern Norway. A group of 7 healthy male subjects was studied in regard to sleep stages and 24 h plasma cortisol and growth hormone patterns during the 4 seasons of the year in an Arctic environment (Troms\u00f8, Norway). No difference in total sleep or sleep stage per cents was found for any of the yearly seasons. A small but statistical significant increase in mean plasma cortisol concentration and amount secreted for 24 h was found for the autumn-winter seasons, as compared with the spring and summer. However, no difference in the circadian curve of cortisol hormonal pattern was found. All subjects secreted growth hormone shortly after sleep onset at night and no difference was found as a function of season of the year."} {"id": "PMID:163565", "title": "Virilizing adrenocortical adenoma responsive to gonadotrophin.", "content": "A virilizing adrenocortical adenoma was demonstrated in a yound female. Urinary 17-ketosteroid excretion and subfractions, plasma testosterone level and urinary 17-ketogenic steroid excretion were markedly increased. Dehydroepiandrosterone was the main constituent of the androgen excess. Otherwise the adrenocortical function was found to be normal as evaluated from measurements of cortisol, corticosterone and their metabolites under basal conditions and during dynamic tests. The androgen excess showed an unexpected response to trophic hormones. Human chorionic gonadotrophin stimulation resulted in a pronounced increase in androgen production, whereas no gonadotrophin-dependency could be demonstrated by means of the oestrogen suppression test. Similarly, no corticotrophin-dependency could be demonstrated by corticotrophin stimulation and suppression tests. Removal of the tumour resulted in normalization of the androgen production and no abnormal response upon human chorionic gonadotrophin administration could now be found. The inappropriate response of tumours to trophic hormones is discussed. It is concluded that the reliability of stimulation and suppression tests in determining the site of excessive androgen production should be accepted with reservation.", "contents": "Virilizing adrenocortical adenoma responsive to gonadotrophin. A virilizing adrenocortical adenoma was demonstrated in a yound female. Urinary 17-ketosteroid excretion and subfractions, plasma testosterone level and urinary 17-ketogenic steroid excretion were markedly increased. Dehydroepiandrosterone was the main constituent of the androgen excess. Otherwise the adrenocortical function was found to be normal as evaluated from measurements of cortisol, corticosterone and their metabolites under basal conditions and during dynamic tests. The androgen excess showed an unexpected response to trophic hormones. Human chorionic gonadotrophin stimulation resulted in a pronounced increase in androgen production, whereas no gonadotrophin-dependency could be demonstrated by means of the oestrogen suppression test. Similarly, no corticotrophin-dependency could be demonstrated by corticotrophin stimulation and suppression tests. Removal of the tumour resulted in normalization of the androgen production and no abnormal response upon human chorionic gonadotrophin administration could now be found. The inappropriate response of tumours to trophic hormones is discussed. It is concluded that the reliability of stimulation and suppression tests in determining the site of excessive androgen production should be accepted with reservation."} {"id": "PMID:163566", "title": "Dissociation of in vivo and in vitro \"autonomy\" in human adrenocortical tumour.", "content": "The diagnosis of Cushing's syndrome due to \"autonomous adrenocortical tumour\" has been established in a patient by appropriate examinations (especially dexamethasone suppression test, ACTH stimulation test, ACTH measurement by radioimmunoassay). Isolated cells have been prepared from a piece of the tumour by a trypsin technique so that the action of ACTH on steriodogenesis in these cells could be studied in vitro. Basal production of corticosteroids by the isolated tumour cells was low (0.3 mu plus or minus 0.04/2 h/10-5 cells). Addition of ACTH induced a dose-dependent stimulation of corticosteroid production. The tumour cells appeared to be unable to produce corticosteroids in the absence of ACTH; maximal production was rather low (1.38 mu plus or minus 0.07/2 h/10-5 cells). A possible explanation for the discrepancies between endocrine function tests and the results of the in vitro studies is given.", "contents": "Dissociation of in vivo and in vitro \"autonomy\" in human adrenocortical tumour. The diagnosis of Cushing's syndrome due to \"autonomous adrenocortical tumour\" has been established in a patient by appropriate examinations (especially dexamethasone suppression test, ACTH stimulation test, ACTH measurement by radioimmunoassay). Isolated cells have been prepared from a piece of the tumour by a trypsin technique so that the action of ACTH on steriodogenesis in these cells could be studied in vitro. Basal production of corticosteroids by the isolated tumour cells was low (0.3 mu plus or minus 0.04/2 h/10-5 cells). Addition of ACTH induced a dose-dependent stimulation of corticosteroid production. The tumour cells appeared to be unable to produce corticosteroids in the absence of ACTH; maximal production was rather low (1.38 mu plus or minus 0.07/2 h/10-5 cells). A possible explanation for the discrepancies between endocrine function tests and the results of the in vitro studies is given."} {"id": "PMID:163567", "title": "Oestradiol-17 beta uptake in vitro into the nuclei of endometrium from different regions of the human uterus.", "content": "Specimens of endometrium from the vault, body and lower body regions of the same human uteri were incubated separately for 30 min in vitro in the presence of 1-6 times 10-9 M 3H-oestradiol. Uptake into the nuclei was variable but in general the vault region endometrium was least active in nuclear accumulation of the hormone, especially in secretory phase endometrium. This suggests that intra-uterine variations found in oestradiol uptake in vivo are due to regional differences in the state of the tissue itself.", "contents": "Oestradiol-17 beta uptake in vitro into the nuclei of endometrium from different regions of the human uterus. Specimens of endometrium from the vault, body and lower body regions of the same human uteri were incubated separately for 30 min in vitro in the presence of 1-6 times 10-9 M 3H-oestradiol. Uptake into the nuclei was variable but in general the vault region endometrium was least active in nuclear accumulation of the hormone, especially in secretory phase endometrium. This suggests that intra-uterine variations found in oestradiol uptake in vivo are due to regional differences in the state of the tissue itself."} {"id": "PMID:163570", "title": "The sick-sinus syndrome in Africans.", "content": "Fifteen cases of the sick-sinus syndrome in young Negroes are presented. The etiology was unknown in all cases; organic heart disease was absent. The very high default rate suggests that the prognosis may be grave. This disorder is by no means uncommon in young persons in tropical countries and the dangers of a mistaken diagnosis of epilepsy or a psychiatric illness have been emphasized. In the absence of an artificial pacemaker, it is suggested that sympathomimetic drugs, while not affecting the heart rate, may be useful in reducing the frequency of syncopal attacks.", "contents": "The sick-sinus syndrome in Africans. Fifteen cases of the sick-sinus syndrome in young Negroes are presented. The etiology was unknown in all cases; organic heart disease was absent. The very high default rate suggests that the prognosis may be grave. This disorder is by no means uncommon in young persons in tropical countries and the dangers of a mistaken diagnosis of epilepsy or a psychiatric illness have been emphasized. In the absence of an artificial pacemaker, it is suggested that sympathomimetic drugs, while not affecting the heart rate, may be useful in reducing the frequency of syncopal attacks."} {"id": "PMID:163571", "title": "Bronchiolo-alveolar carcinoma-cell of origin.", "content": "Bronchiolo-alveolar carcinoma is the least common of the primary pulmonary carcinomas, and there is controversy as to its cell of origin. In this light- and electron microscopic study of five bronchiolo-alveolar carcinomas, at least two cell types were found, both of bronchiolar origin. One cell type is a metaplastic bronchiolar mucous cell and the other a bronchiolar stem cell that has ultrastructural features of both the respiratory ciliated and the respiratory nonciliated (\"Clara\") cell. It would not be unusual if tumors of the bronchiolo-alveolar region differentiate into cells of either the bronchiole or the alveolus, for embryologically they have a common origin. However, as information about the ultrastructure of these tumors accumulates, it is becoming apparent that an alveolar-cell carcinoma must be a rare occurrence. Hyperplastic Type II aleveolar epithelial cells may be found about the margins of these tumors and can be mistaken for the neoplastic cells.", "contents": "Bronchiolo-alveolar carcinoma-cell of origin. Bronchiolo-alveolar carcinoma is the least common of the primary pulmonary carcinomas, and there is controversy as to its cell of origin. In this light- and electron microscopic study of five bronchiolo-alveolar carcinomas, at least two cell types were found, both of bronchiolar origin. One cell type is a metaplastic bronchiolar mucous cell and the other a bronchiolar stem cell that has ultrastructural features of both the respiratory ciliated and the respiratory nonciliated (\"Clara\") cell. It would not be unusual if tumors of the bronchiolo-alveolar region differentiate into cells of either the bronchiole or the alveolus, for embryologically they have a common origin. However, as information about the ultrastructure of these tumors accumulates, it is becoming apparent that an alveolar-cell carcinoma must be a rare occurrence. Hyperplastic Type II aleveolar epithelial cells may be found about the margins of these tumors and can be mistaken for the neoplastic cells."} {"id": "PMID:163572", "title": "Pyrophosphate arthropathy.", "content": "A scanning electron microscopic study of six cases of pyrophosphate arthropathy has been conducted. In the majority of cases the crystals were rectangular. In some cases giant crystals were present. In one case, the crystals were pyramidal. It is concluded that many geometrically different forms of calcium pyrophosphate crystal exist and that the scanning electron microscope is a useful tool in the differentiation of pyrophosphate arthropathy from other forms of crystal synovitis.", "contents": "Pyrophosphate arthropathy. A scanning electron microscopic study of six cases of pyrophosphate arthropathy has been conducted. In the majority of cases the crystals were rectangular. In some cases giant crystals were present. In one case, the crystals were pyramidal. It is concluded that many geometrically different forms of calcium pyrophosphate crystal exist and that the scanning electron microscope is a useful tool in the differentiation of pyrophosphate arthropathy from other forms of crystal synovitis."} {"id": "PMID:163574", "title": "An outbreak of severe pneumonia due to respiratory syncytial virus in isolated Arctic populations.", "content": "A rapidly developing outbreak of pneumonia in young infants was documented in two isolated Artic populations in May 1972. These were studied virologically, serologically and clinically. In addition to the two stricken communities, one apparently unaffected with serious clinical illness and a fourth, in which are located the major hospital and airport in the eastern Arctic, were also studied. One hundred and twenty-four patients were studied serologically and 81 respiratory and other specimens were obtained for virus isolation from 40 of these patients. Clinical records were kept of the outbreak in each area and a detailed questionnaire was filled out for 140 children and their families. Respiratory syncytial irus (RSV) was cultured from eight ill children. Electron microscopy provided the first evidence of RSV infection. A seroconversion rate of approximately 50% was seen in both affected communities as well as in the clinically unaffected one. The epidemic in the first two communities was characterized by severe pneumonia and frequent hospitalization but no cases of bronchiolitis were seen. No evidence for other causes of this outbreak could be obtained by testing for antibodies to influenza A and B, parainfluenza 1, 2 and 3, adenovirus and herpes simplex viruses. Unusual features of this epidemic of RSV infection include the high attack rate, severe morbidity, illness manifest almost exclusively as pneumonia rather than bronchiolitis and the difference between the expression of disease in different communities. Historical data and clinical observations were inadequate to explain these unusual features.", "contents": "An outbreak of severe pneumonia due to respiratory syncytial virus in isolated Arctic populations. A rapidly developing outbreak of pneumonia in young infants was documented in two isolated Artic populations in May 1972. These were studied virologically, serologically and clinically. In addition to the two stricken communities, one apparently unaffected with serious clinical illness and a fourth, in which are located the major hospital and airport in the eastern Arctic, were also studied. One hundred and twenty-four patients were studied serologically and 81 respiratory and other specimens were obtained for virus isolation from 40 of these patients. Clinical records were kept of the outbreak in each area and a detailed questionnaire was filled out for 140 children and their families. Respiratory syncytial irus (RSV) was cultured from eight ill children. Electron microscopy provided the first evidence of RSV infection. A seroconversion rate of approximately 50% was seen in both affected communities as well as in the clinically unaffected one. The epidemic in the first two communities was characterized by severe pneumonia and frequent hospitalization but no cases of bronchiolitis were seen. No evidence for other causes of this outbreak could be obtained by testing for antibodies to influenza A and B, parainfluenza 1, 2 and 3, adenovirus and herpes simplex viruses. Unusual features of this epidemic of RSV infection include the high attack rate, severe morbidity, illness manifest almost exclusively as pneumonia rather than bronchiolitis and the difference between the expression of disease in different communities. Historical data and clinical observations were inadequate to explain these unusual features."} {"id": "PMID:163575", "title": "Immunologic significance of the mumps virus skin test in infants, children and adults.", "content": "The biologic validity of cell-mediated immunity to mumps virus was evaluated in 395 children, adolescents and adults. The study protocol included the determination of cutaneous delayed hypersensitivity to viral and avian control antigens and in 79% of the subjects an essential double bleeding was performed before and after mumps virus skin test for assay of neutralizing antibody. Seven per cent of subjects expressed sufficient delayed hypersentitivity to the control antigen to erase an apparently positive mumps virus skin test. Anamnestic conversions from seronegativity to seropositivity, elicited by the mumps virus skin test, increased from 4% in children to 25% in adults, which suggests waning B-cell recognition of prior mumps virus infection in adults. Although pregnancy diminished the difference (p smaller than .001), adults showed greater cutaneous delayed hypersensitivity to mumps virus antigen than did children (p smaller than .001), suggesting that mumps virus reinfection or persistence induced the escalation of more sensitive T-cell recognition with increasing age. Humoral immunity, assessed by the double bleeding technique in the vast majority of individuals, rose form 16% (1-4 years), 45% (5-9 years) and 80% (10-14 years) to 94% in adolescents and adults. Ordinarily 75-95% in other age groups, the decline of correlation between mumps virus cellular and humoral immunity to 60% in school children may result from prior parainfluenza virus infection, inconsistent potency of the skin test antigen, concurrent immunosuppressive infection, and lagging induction of mumps virus cellular immunity in recently infected individuals. Immunologic study of a large colony of subhuman primates failed to establish an hierarchial antigenic interrelationship among mumps virus and two additional paramyxoviruses.", "contents": "Immunologic significance of the mumps virus skin test in infants, children and adults. The biologic validity of cell-mediated immunity to mumps virus was evaluated in 395 children, adolescents and adults. The study protocol included the determination of cutaneous delayed hypersensitivity to viral and avian control antigens and in 79% of the subjects an essential double bleeding was performed before and after mumps virus skin test for assay of neutralizing antibody. Seven per cent of subjects expressed sufficient delayed hypersentitivity to the control antigen to erase an apparently positive mumps virus skin test. Anamnestic conversions from seronegativity to seropositivity, elicited by the mumps virus skin test, increased from 4% in children to 25% in adults, which suggests waning B-cell recognition of prior mumps virus infection in adults. Although pregnancy diminished the difference (p smaller than .001), adults showed greater cutaneous delayed hypersensitivity to mumps virus antigen than did children (p smaller than .001), suggesting that mumps virus reinfection or persistence induced the escalation of more sensitive T-cell recognition with increasing age. Humoral immunity, assessed by the double bleeding technique in the vast majority of individuals, rose form 16% (1-4 years), 45% (5-9 years) and 80% (10-14 years) to 94% in adolescents and adults. Ordinarily 75-95% in other age groups, the decline of correlation between mumps virus cellular and humoral immunity to 60% in school children may result from prior parainfluenza virus infection, inconsistent potency of the skin test antigen, concurrent immunosuppressive infection, and lagging induction of mumps virus cellular immunity in recently infected individuals. Immunologic study of a large colony of subhuman primates failed to establish an hierarchial antigenic interrelationship among mumps virus and two additional paramyxoviruses."} {"id": "PMID:163577", "title": "The role of renal adenosine 3',5'-monophosphate in the control of erythropoietin production.", "content": "A regulatory role for adenosine 3',5'-monophosphate (cyclic AMP) in the production of the renal hormone rythropoietin following erythropoietic stimulation with cobaltous chloride hexahydrate is proposed. Studies in rates reveal a temporal relationship between renal cyclic AMP levels and plasma titers of erythropoietin. In addition, cobalt increases the activity of an erythropoietin-generating enzyme (renal erythropoietic factor) with maximal enzyme activity occurring after the rise in cyclic AMP levels but before the increase in erythropoietin titers. This increase in renal cyclic AMP is localized to the renal cortex. Cobalt stimulates renal cortical adenylate cyclase but has no effect on renal cyclic nucleotide phosphodiesterase. The addition of cyclic AMP (3 time 10-6 M) and a partially purified cyclic AMP-dependent protein kinase from rat kidney to an inactive preparation of renal erythropoietic factor increases the ability of renal erythropoietic factor to generate erythropoietin. Data from the polycythemic mouse assay, a bioassay used to quantitate erythropoietic activity of test substances, indicate that dibutyryl cyclic AMP is erythropoietically active with respect to its ability to increase radioactive-labelled iron (59Fe) incorporation into heme of newly formed red blood cells. Theophylline, which by itself is erythropoietically inactive, potentiated the erythropoietic effect of cobalt in polycythemic mice. These results suggest that cyclic AMP plays a significant role in the renal production of erythropoietin following cobalt administration. It is postulated that cobalt stimulates renal cortical adenyoate cyclase, thus increasing renal cyclic AMP levels. Cyclic AMP then activates a protein kinase which subsequently stimulates renal erythropoietic factor to generate erythropoietin. A similar cyclic AMP mechanism may be operative after erythropoietic stimulation by exposure to hypoxia or prostaglandin treatment.", "contents": "The role of renal adenosine 3',5'-monophosphate in the control of erythropoietin production. A regulatory role for adenosine 3',5'-monophosphate (cyclic AMP) in the production of the renal hormone rythropoietin following erythropoietic stimulation with cobaltous chloride hexahydrate is proposed. Studies in rates reveal a temporal relationship between renal cyclic AMP levels and plasma titers of erythropoietin. In addition, cobalt increases the activity of an erythropoietin-generating enzyme (renal erythropoietic factor) with maximal enzyme activity occurring after the rise in cyclic AMP levels but before the increase in erythropoietin titers. This increase in renal cyclic AMP is localized to the renal cortex. Cobalt stimulates renal cortical adenylate cyclase but has no effect on renal cyclic nucleotide phosphodiesterase. The addition of cyclic AMP (3 time 10-6 M) and a partially purified cyclic AMP-dependent protein kinase from rat kidney to an inactive preparation of renal erythropoietic factor increases the ability of renal erythropoietic factor to generate erythropoietin. Data from the polycythemic mouse assay, a bioassay used to quantitate erythropoietic activity of test substances, indicate that dibutyryl cyclic AMP is erythropoietically active with respect to its ability to increase radioactive-labelled iron (59Fe) incorporation into heme of newly formed red blood cells. Theophylline, which by itself is erythropoietically inactive, potentiated the erythropoietic effect of cobalt in polycythemic mice. These results suggest that cyclic AMP plays a significant role in the renal production of erythropoietin following cobalt administration. It is postulated that cobalt stimulates renal cortical adenyoate cyclase, thus increasing renal cyclic AMP levels. Cyclic AMP then activates a protein kinase which subsequently stimulates renal erythropoietic factor to generate erythropoietin. A similar cyclic AMP mechanism may be operative after erythropoietic stimulation by exposure to hypoxia or prostaglandin treatment."} {"id": "PMID:163578", "title": "The kidney as an endocrine organ involved in the function of vitamin D.", "content": "Vitamin D3 must be metabilically altered first in the liver to 25-hydroxyvitamin D3 (25 OH-D3) and subsequently in the kidney to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) before it can function. Because 1,25-(OH)2D3 is formed in the kidney and acts in intestine and bone to elevate serum calcium and phosphate concentrations, it can be considered a hormone. The production of 1,25-(OH)2D3 is feedback regulated either directly or indirectly by serum calcium and serum phosphate concentrations. The hypocalcemic regulation is mediated by the parathyroid glands. The hypophosphatemic stimulus, however, does not involve either the parathyroid or thyroid glands. Under conditions whereby the synthesis of 1,25-(OH)2D3 is repressed, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3 is formed. This metabolite can be converted further to 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3D3), which stimulate intestinal calcium transport but not bone calcium mobilization or phosphate transport reactions. A number of vitamin D-resistant bone diseases may be related to defective vitamin D metabolism. For example, bone disease related to choric renal failure likely results from defective formation of 1,25-(OH)2D3 in the kidney. Treatment of this disease with intravenously administered 1,25-(OH)2D3 is effective in correcting the bone lesions. 1Alpha-hydroxyvitamin D3 (1alpha-OH-D3), a new synthetic analog of 1,25-(OH)2D3 which is less expensive to produce than 1,25-(OH)2D3, is effective in anephric animals and may have several advantages over 1,25-(OH)2D3 in treating bone diseases.", "contents": "The kidney as an endocrine organ involved in the function of vitamin D. Vitamin D3 must be metabilically altered first in the liver to 25-hydroxyvitamin D3 (25 OH-D3) and subsequently in the kidney to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) before it can function. Because 1,25-(OH)2D3 is formed in the kidney and acts in intestine and bone to elevate serum calcium and phosphate concentrations, it can be considered a hormone. The production of 1,25-(OH)2D3 is feedback regulated either directly or indirectly by serum calcium and serum phosphate concentrations. The hypocalcemic regulation is mediated by the parathyroid glands. The hypophosphatemic stimulus, however, does not involve either the parathyroid or thyroid glands. Under conditions whereby the synthesis of 1,25-(OH)2D3 is repressed, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3 is formed. This metabolite can be converted further to 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3D3), which stimulate intestinal calcium transport but not bone calcium mobilization or phosphate transport reactions. A number of vitamin D-resistant bone diseases may be related to defective vitamin D metabolism. For example, bone disease related to choric renal failure likely results from defective formation of 1,25-(OH)2D3 in the kidney. Treatment of this disease with intravenously administered 1,25-(OH)2D3 is effective in correcting the bone lesions. 1Alpha-hydroxyvitamin D3 (1alpha-OH-D3), a new synthetic analog of 1,25-(OH)2D3 which is less expensive to produce than 1,25-(OH)2D3, is effective in anephric animals and may have several advantages over 1,25-(OH)2D3 in treating bone diseases."} {"id": "PMID:163580", "title": "The protean manifestations of Mycoplasma pneumoniae infection in adults.", "content": "Mycoplasma pneumoniae is a well recognized respiratory pathogen in children and young adults. In addition, M. pneumoniae infections may also involve other organ systems. Reviewed here are the various clinical syndromes in adults caused by this infectious agent, with emphasis on those which have recently been seen at The New York Hospital. Two previously unreported manifestations of M. pneumoniae infection, cranial nerve mononeuropathy and hepatitis, are described, and the laboratory methods for diagnosis are discussed.", "contents": "The protean manifestations of Mycoplasma pneumoniae infection in adults. Mycoplasma pneumoniae is a well recognized respiratory pathogen in children and young adults. In addition, M. pneumoniae infections may also involve other organ systems. Reviewed here are the various clinical syndromes in adults caused by this infectious agent, with emphasis on those which have recently been seen at The New York Hospital. Two previously unreported manifestations of M. pneumoniae infection, cranial nerve mononeuropathy and hepatitis, are described, and the laboratory methods for diagnosis are discussed."} {"id": "PMID:163581", "title": "American Burkitt's lymphoma: a clinicopathologic study of 30 cases. II. Pathologic correlations.", "content": "Thirty cases of malignant lymphoma, undifferentiated, Burkitt's type are reviewed. An older median age and a predominance of presentation in abdominal and pelvic sites rather than in the jaw distinguishes this series of American patients from those reported from endemic regions in Africa. Bone marrow involvement invariably consisted of massive infiltration recognizable in smear, clot and biopsy preparations. Involvement of the central nervous system or bone marrow was always associated with short survival. In all eight long-term survivors lymphoma was apparently confined to a single site at presentation. At autopsy, the most consistent finding was widespread multiorgan involvement without predilection for lymphoreticular structures. The histologic appearance of the tumor changed after chemotherapy, varying from diffuse necrosis within 48 hours of initial therapy to extreme pleomorphism of tumor cells after 9 months of therapy. In one patient, there was almost complete absence of lymphoma at autopsy in an organ site shown clinically to have been extensively involved by tumor prior to treatment. The diagnostic and therapeutic implications of these findings are discussed.", "contents": "American Burkitt's lymphoma: a clinicopathologic study of 30 cases. II. Pathologic correlations. Thirty cases of malignant lymphoma, undifferentiated, Burkitt's type are reviewed. An older median age and a predominance of presentation in abdominal and pelvic sites rather than in the jaw distinguishes this series of American patients from those reported from endemic regions in Africa. Bone marrow involvement invariably consisted of massive infiltration recognizable in smear, clot and biopsy preparations. Involvement of the central nervous system or bone marrow was always associated with short survival. In all eight long-term survivors lymphoma was apparently confined to a single site at presentation. At autopsy, the most consistent finding was widespread multiorgan involvement without predilection for lymphoreticular structures. The histologic appearance of the tumor changed after chemotherapy, varying from diffuse necrosis within 48 hours of initial therapy to extreme pleomorphism of tumor cells after 9 months of therapy. In one patient, there was almost complete absence of lymphoma at autopsy in an organ site shown clinically to have been extensively involved by tumor prior to treatment. The diagnostic and therapeutic implications of these findings are discussed."} {"id": "PMID:163582", "title": "Clinical evaluation of patients with infectious mononucleosis and development of antibodies to the R component of the Epstein-Barr virus-induced early antigen complex.", "content": "Previous reports have emphasized that the transitory antibody responses to Epstein-Barr virus (EBV)-induced early antigens (EA) in the course of infectious mononucleosis are usually directed against the D (diffuse) component of the EA complex. In this report clinical and serologic data have been presented on 14 patients with infectious mononucleosis who responded either solely with antibodies to the R (restricted) component of the EA complex or revealed anti-R after the initial anti-D responses had subsided weeks or months after onset of the disease. Anti-R persisted usually for many months , as many as 39, but in some patients it was no longer detectable in late follow-up serum spectimens. Although many patients had an unremarkable course of illness, others, mostly those with late anti-R responses, showed unusual or protracted clinical manifestations and several complained over periods of 4 to 28 months of recurrent symptoms resembling those experienced during the acute stage of disease. The presence of anti-R and the relatively high continuous titers of antibodies to EB viral capsid antigens (VCA) may reflect a more than usual, persistent EBV activity which, in turn, may account for the recurrent symptoms.", "contents": "Clinical evaluation of patients with infectious mononucleosis and development of antibodies to the R component of the Epstein-Barr virus-induced early antigen complex. Previous reports have emphasized that the transitory antibody responses to Epstein-Barr virus (EBV)-induced early antigens (EA) in the course of infectious mononucleosis are usually directed against the D (diffuse) component of the EA complex. In this report clinical and serologic data have been presented on 14 patients with infectious mononucleosis who responded either solely with antibodies to the R (restricted) component of the EA complex or revealed anti-R after the initial anti-D responses had subsided weeks or months after onset of the disease. Anti-R persisted usually for many months , as many as 39, but in some patients it was no longer detectable in late follow-up serum spectimens. Although many patients had an unremarkable course of illness, others, mostly those with late anti-R responses, showed unusual or protracted clinical manifestations and several complained over periods of 4 to 28 months of recurrent symptoms resembling those experienced during the acute stage of disease. The presence of anti-R and the relatively high continuous titers of antibodies to EB viral capsid antigens (VCA) may reflect a more than usual, persistent EBV activity which, in turn, may account for the recurrent symptoms."} {"id": "PMID:163583", "title": "Fanconi syndrome in adults. A manifestation of a latent form of myeloma.", "content": "From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.", "contents": "Fanconi syndrome in adults. A manifestation of a latent form of myeloma. From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded."} {"id": "PMID:163584", "title": "Aberrant hormone activity by tumors of gynecologic importance.", "content": "Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances.", "contents": "Aberrant hormone activity by tumors of gynecologic importance. Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances."} {"id": "PMID:163585", "title": "Carcinoembryonic antigen in patients with gynecologic malignancies.", "content": "The determination of carcinoembryonic antigen (CEA) in plasma has been of much interest currently concomitant with the search for an immunologic diagnosis test. Recent reports have shed some doubt on the specificity of carcinoembryonic antigens for gastrointestinal tract malignancies. This report details the plasma CEA values in 341 patients with varying gynecologic malignancies. These studies have demonstrated that plasma CEA is elevated in close to 50 per cent of patients with invasive gynecologic cancer. The incidence of positive values is appreciably higher in the advanced stages of disease. Of particular interest was that 84 per cent (21 of 25) of the patients with recurrent squamous-cell carcinoma of the cervix had a positive CEA value. Similar results were found in patients with cancer of the vulva, ovary, and endometrium.", "contents": "Carcinoembryonic antigen in patients with gynecologic malignancies. The determination of carcinoembryonic antigen (CEA) in plasma has been of much interest currently concomitant with the search for an immunologic diagnosis test. Recent reports have shed some doubt on the specificity of carcinoembryonic antigens for gastrointestinal tract malignancies. This report details the plasma CEA values in 341 patients with varying gynecologic malignancies. These studies have demonstrated that plasma CEA is elevated in close to 50 per cent of patients with invasive gynecologic cancer. The incidence of positive values is appreciably higher in the advanced stages of disease. Of particular interest was that 84 per cent (21 of 25) of the patients with recurrent squamous-cell carcinoma of the cervix had a positive CEA value. Similar results were found in patients with cancer of the vulva, ovary, and endometrium."} {"id": "PMID:163586", "title": "Effect of progesterone on estrogen receptors in the rabbit uterus.", "content": "The macromolecular binding of estradiol was investigated in the rabbit uterus under various hormonal states in a search for evidence of progesterone antagonism of the estrogen-receptor complex interaction. Progesterone did not alter the sucrose gradient sedimentation characteristics of the estrogen-receptor complex in estrus or castrate animals. Progesterone treatment of castrated animals did not alter the absolute number of EBS (estrogen-binding sites) per cell, but did result in decreased relative concentration of EBS by increasing the soluble protein content of the cells over that seen in untreated castrates. Castration did not alter the absolute number of EBS per cell but did increase the relative concentration of estrogen binding in the cytosol.", "contents": "Effect of progesterone on estrogen receptors in the rabbit uterus. The macromolecular binding of estradiol was investigated in the rabbit uterus under various hormonal states in a search for evidence of progesterone antagonism of the estrogen-receptor complex interaction. Progesterone did not alter the sucrose gradient sedimentation characteristics of the estrogen-receptor complex in estrus or castrate animals. Progesterone treatment of castrated animals did not alter the absolute number of EBS (estrogen-binding sites) per cell, but did result in decreased relative concentration of EBS by increasing the soluble protein content of the cells over that seen in untreated castrates. Castration did not alter the absolute number of EBS per cell but did increase the relative concentration of estrogen binding in the cytosol."} {"id": "PMID:163589", "title": "Hormones in human pregnancy. IV. Plasma progesterone.", "content": "The plasma concentration of progesterone (P) has been measured by radioimmunoassay in maternal peripheral vein (M.P.V.) at early pregnancy and in M.P.V. umbilical artery (U.A.) and umbilical vein (U.V.) at term pregnancy. In early preganacy marked hour-to-hour fluctuation of plasma progesterone was noted. At term pregnancy plasma P levels of U.V. were higher than those of U.A. and the umbilical venous arterial differences of plasma P did not differ between male and femal fetuses. Administration of hydrocortisone and ACTH to patients scheduled to undergo cesarean section had no effect on M.P.V., U.A., and U.V. plasma P concentration. On the basis of the differences between U.V. and U.A. plasma P concentrations and reported umbilical flow it was estimated that the secretion rate of P into the fetal circulation is approximately 23 mg. per 24 hr. and would amount to approximately 10 per cent of the reported total daily production rate of P at term pregnancy. The fraction of P which is unbound to the plasma proteins was estimeated by equilibrium dialysis at 37 degrees C. The per cent unbound P in M.P.V. plasma of pregnant patients at term was not different from that of nonpregnant patients but was 40 per cent lower than that in umbilical cord plasma (P LESS THAN 0.01), and the ratio between the concentrations of unbound P and estradiol in M.P.V. increased as pregnancy progressed. Plasma P in re-eclamptic patients who subsequently sustained intrauterine fetal death had no value in assessing placental function.", "contents": "Hormones in human pregnancy. IV. Plasma progesterone. The plasma concentration of progesterone (P) has been measured by radioimmunoassay in maternal peripheral vein (M.P.V.) at early pregnancy and in M.P.V. umbilical artery (U.A.) and umbilical vein (U.V.) at term pregnancy. In early preganacy marked hour-to-hour fluctuation of plasma progesterone was noted. At term pregnancy plasma P levels of U.V. were higher than those of U.A. and the umbilical venous arterial differences of plasma P did not differ between male and femal fetuses. Administration of hydrocortisone and ACTH to patients scheduled to undergo cesarean section had no effect on M.P.V., U.A., and U.V. plasma P concentration. On the basis of the differences between U.V. and U.A. plasma P concentrations and reported umbilical flow it was estimated that the secretion rate of P into the fetal circulation is approximately 23 mg. per 24 hr. and would amount to approximately 10 per cent of the reported total daily production rate of P at term pregnancy. The fraction of P which is unbound to the plasma proteins was estimeated by equilibrium dialysis at 37 degrees C. The per cent unbound P in M.P.V. plasma of pregnant patients at term was not different from that of nonpregnant patients but was 40 per cent lower than that in umbilical cord plasma (P LESS THAN 0.01), and the ratio between the concentrations of unbound P and estradiol in M.P.V. increased as pregnancy progressed. Plasma P in re-eclamptic patients who subsequently sustained intrauterine fetal death had no value in assessing placental function."} {"id": "PMID:163590", "title": "On the regulation of fetal and maternal 16 alpha- hydroxydehydroepiandrosterone and its sulfate by cortisol and ACTH in human pregnancy at term.", "content": "In studying the mechanisms which govern estriol production in human pregnancy at term, 16 alpha OH-DHEA, 16alpha-OH-DHEA sulfate, and unbound unconjugated cortisol were measured in peripheral venous plasma of 28 healthy women and in cord venous and arterial plasms of their newborn infants at the time of elective cesarean section prior to the onset of labor. In eight cases treated with 150 mg. of cortisol, maternal and cord plasma 16alpha-OH-DHEA and its sulfate were considerably lower than in 10 control cases. Approximately 4 to 8 1/2 hours after injection of 40 I.U. of Depot-ACTH, both of these estriol precursors were also significantly decreased. It is concluded from these experiments that cortisol causes a decrease of estriol mainly by suppressing fetal 16alpha-OH-DS.", "contents": "On the regulation of fetal and maternal 16 alpha- hydroxydehydroepiandrosterone and its sulfate by cortisol and ACTH in human pregnancy at term. In studying the mechanisms which govern estriol production in human pregnancy at term, 16 alpha OH-DHEA, 16alpha-OH-DHEA sulfate, and unbound unconjugated cortisol were measured in peripheral venous plasma of 28 healthy women and in cord venous and arterial plasms of their newborn infants at the time of elective cesarean section prior to the onset of labor. In eight cases treated with 150 mg. of cortisol, maternal and cord plasma 16alpha-OH-DHEA and its sulfate were considerably lower than in 10 control cases. Approximately 4 to 8 1/2 hours after injection of 40 I.U. of Depot-ACTH, both of these estriol precursors were also significantly decreased. It is concluded from these experiments that cortisol causes a decrease of estriol mainly by suppressing fetal 16alpha-OH-DS."} {"id": "PMID:163592", "title": "Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics.", "content": "Cells derived from human atherosclerotic plaques and from arterial media were compared with cells obtained from human leiomyomata and myometrium with respect to growth behavior in long-term cell culture. None of numerous variations in culture media, including alterations of serum concentration and source, improved the rate of cell multiplication or in vitro longevity. Both uterine cell types, but neither arterial cell type, multiplied after tissue dissociation with enzymes (elastase, collagenase, hyaluronidase). The replicative life-span of each of eight samples of arterial plaque cells was equal to or less than that of the corresponding medial cells. A similar relationship was observed for eight paired sets of leiomyoma and myometrial cells. The results indicate that, under the conditions of culture in vitro, cells of a bona fide smooth muscle tumor have a finite replicative life-span and smooth muscle cells of atherosclerotic plaques behave in a similar manner.", "contents": "Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics. Cells derived from human atherosclerotic plaques and from arterial media were compared with cells obtained from human leiomyomata and myometrium with respect to growth behavior in long-term cell culture. None of numerous variations in culture media, including alterations of serum concentration and source, improved the rate of cell multiplication or in vitro longevity. Both uterine cell types, but neither arterial cell type, multiplied after tissue dissociation with enzymes (elastase, collagenase, hyaluronidase). The replicative life-span of each of eight samples of arterial plaque cells was equal to or less than that of the corresponding medial cells. A similar relationship was observed for eight paired sets of leiomyoma and myometrial cells. The results indicate that, under the conditions of culture in vitro, cells of a bona fide smooth muscle tumor have a finite replicative life-span and smooth muscle cells of atherosclerotic plaques behave in a similar manner."} {"id": "PMID:163593", "title": "Immunohistochemical demonstration of serine dehydratase in rat liver.", "content": "Serine dehydratase (L-serine hydro-lyase, EC 4.2.1.13) WAS DEMONSTRATED IN LIVER TISSUE OF RATS BY AN INdirect immunofluorescent method. In the adult rat liver, serine dehydratase was localized to periportal hepatocytes, diffusely in their cytoplasm. The enzyme-specific fluorescence was absent or extremely low in the centrolobular hepatocytes. It was not demonstrated in nonparenchymal cells. Feeding a 90% protein diet for 5 days caused marked induction of this enzyme in the periportal and midzonal hepatocytes but no induction in the centrolobular hepatocytes. In the newborn rat liver, there was no apparent intralobular heterogeneity seen in the distribution of serine dehydratase, either before or after dietary induction. After 1 week of age, there was a gradual development of the intralobular hetero-geneity of the enzyme, which was emphasized by dietary stimulation. A comparative study of the induction pattern between the livers of intact and adrenalectomized rats suggested that there is no heterogeneity among serine-dehydratase-positive cells with respect to hormonal regulation of this enzyme by either glucagon or cortisone.", "contents": "Immunohistochemical demonstration of serine dehydratase in rat liver. Serine dehydratase (L-serine hydro-lyase, EC 4.2.1.13) WAS DEMONSTRATED IN LIVER TISSUE OF RATS BY AN INdirect immunofluorescent method. In the adult rat liver, serine dehydratase was localized to periportal hepatocytes, diffusely in their cytoplasm. The enzyme-specific fluorescence was absent or extremely low in the centrolobular hepatocytes. It was not demonstrated in nonparenchymal cells. Feeding a 90% protein diet for 5 days caused marked induction of this enzyme in the periportal and midzonal hepatocytes but no induction in the centrolobular hepatocytes. In the newborn rat liver, there was no apparent intralobular heterogeneity seen in the distribution of serine dehydratase, either before or after dietary induction. After 1 week of age, there was a gradual development of the intralobular hetero-geneity of the enzyme, which was emphasized by dietary stimulation. A comparative study of the induction pattern between the livers of intact and adrenalectomized rats suggested that there is no heterogeneity among serine-dehydratase-positive cells with respect to hormonal regulation of this enzyme by either glucagon or cortisone."} {"id": "PMID:163594", "title": "Nuclear bodies produced in astrocytes by tilorone.", "content": "Large, eosinophilic, nonglycogenic nuclear inclusions were produced in the central nervous system by the drug tilorone. At the light microscope level, the inclusions occurred predominantly in astrocytes. Ultrastructurally, they were identical to the nuclear bodies described in many cell types under many conditions. The bodies were produced by tilorone in small numbers in the median eminence, a part of the hypothalamus that lacks a blood-brain barrier. They were produced in only 2 or 3 days in large numbers adjacent to zones of thermal or traumatic necrosis or in areas of inflammation. These facts, and the distribution of affected astrocytes, indicated that permeability factors and cerebrospinal fluid flow were involved in the development of the nuclear bodies. The large size and large number of nuclear bodies produced by tilorone should facilitate studies of this poorly understood nuclear organelle.", "contents": "Nuclear bodies produced in astrocytes by tilorone. Large, eosinophilic, nonglycogenic nuclear inclusions were produced in the central nervous system by the drug tilorone. At the light microscope level, the inclusions occurred predominantly in astrocytes. Ultrastructurally, they were identical to the nuclear bodies described in many cell types under many conditions. The bodies were produced by tilorone in small numbers in the median eminence, a part of the hypothalamus that lacks a blood-brain barrier. They were produced in only 2 or 3 days in large numbers adjacent to zones of thermal or traumatic necrosis or in areas of inflammation. These facts, and the distribution of affected astrocytes, indicated that permeability factors and cerebrospinal fluid flow were involved in the development of the nuclear bodies. The large size and large number of nuclear bodies produced by tilorone should facilitate studies of this poorly understood nuclear organelle."} {"id": "PMID:163595", "title": "Effect of inhibition of peptidase activity on distribution of intrarenal blood flow.", "content": "Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion.", "contents": "Effect of inhibition of peptidase activity on distribution of intrarenal blood flow. Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion."} {"id": "PMID:163596", "title": "Release of cyclic AMP by toad urinary bladder.", "content": "Cyclic AMP accumulates in the Ringer solution bathing the toad urinary bladder in vitro. At least 4 times more cyclic AMP is released into the solution bathing the serosal surface than into the solution bathing the mucosal surface. Most of the cyclic AMP originates in the epithelial cells rather than the stroma. Vasopressin increased the content of cyclic AMP in the epithelial cells and increases the amount of cyclic AMP in the Ringer solution. Since there is not an increase in medium cyclic AMP when cell cyclic AMP levels are increased by theophylline, it is suggested that theophylline may reduce the permeability of the cell membrane to cyclic AMP. Finally, it is demonstrated that 10 mM NaF increase the amount of cyclic AMP in the epithelial cells and in the solution bathing the bladder, but block the effect of vasopressin on water permeability, presumably at a step subsequent to the formation of cyclic AMP.", "contents": "Release of cyclic AMP by toad urinary bladder. Cyclic AMP accumulates in the Ringer solution bathing the toad urinary bladder in vitro. At least 4 times more cyclic AMP is released into the solution bathing the serosal surface than into the solution bathing the mucosal surface. Most of the cyclic AMP originates in the epithelial cells rather than the stroma. Vasopressin increased the content of cyclic AMP in the epithelial cells and increases the amount of cyclic AMP in the Ringer solution. Since there is not an increase in medium cyclic AMP when cell cyclic AMP levels are increased by theophylline, it is suggested that theophylline may reduce the permeability of the cell membrane to cyclic AMP. Finally, it is demonstrated that 10 mM NaF increase the amount of cyclic AMP in the epithelial cells and in the solution bathing the bladder, but block the effect of vasopressin on water permeability, presumably at a step subsequent to the formation of cyclic AMP."} {"id": "PMID:163597", "title": "Roentgen problems in evaluating the atrophic stomach of the elderly.", "content": "Gastric atrophy in the elderly may cause problems in the interpretation of gastrointestinal studies. Seventeen such cases are reported: 8 patients showed limited distensibility and irregularity of the distal stomach simulating scirrhous carcinoma; 6 patients showed gastric retention of food; and 2 patients showed gastric retention of oral cholecystographic medium. Awareness of these phenomena may prevent serious errors in roentgen diagnosis.", "contents": "Roentgen problems in evaluating the atrophic stomach of the elderly. Gastric atrophy in the elderly may cause problems in the interpretation of gastrointestinal studies. Seventeen such cases are reported: 8 patients showed limited distensibility and irregularity of the distal stomach simulating scirrhous carcinoma; 6 patients showed gastric retention of food; and 2 patients showed gastric retention of oral cholecystographic medium. Awareness of these phenomena may prevent serious errors in roentgen diagnosis."} {"id": "PMID:163600", "title": "Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation.", "content": "Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)", "contents": "Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation. Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)"} {"id": "PMID:163602", "title": "Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis viral isolates from cattle with epididymitis and vaginitis.", "content": "Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis (IBR-IPV) viral isolates were obtained from cattle affected with epididymitis-vaginitis. Isolation of virus from the diseased animals indicated that the genital form of IBR-IPV virus infection exists in Kenya and that epididymitis-vaginitis may be associated with IBR-IPV virus. Serums prepared from cattle having the genital form of the disease did not always have detectable antibody titers.", "contents": "Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis viral isolates from cattle with epididymitis and vaginitis. Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis (IBR-IPV) viral isolates were obtained from cattle affected with epididymitis-vaginitis. Isolation of virus from the diseased animals indicated that the genital form of IBR-IPV virus infection exists in Kenya and that epididymitis-vaginitis may be associated with IBR-IPV virus. Serums prepared from cattle having the genital form of the disease did not always have detectable antibody titers."} {"id": "PMID:163603", "title": "Porcine parvovirus: frequency of naturally occurring transplacental infection and viral contamination of fetal porcine kidney cell cultures.", "content": "The frequency of naturally occurring transplacental infection of swine with porcine parvovirus (PPV) and one of the possible consequences of such infection--the presence of PPV in cell cultures prepared from fetal tissues--were investigated. Transplacental infection was indicated by the presence of high titers of hemagglutination inhibiting (HI) antibody for PPV in serums of 0-day-old, hysterectomy-derived, colostrum-deprived pigs of 3 of 82 litters. All letters were farm-raised dams. Moreover, cell cultures prepared from 3 of 49 lots of fetal porcine kidneys (FPK) collected from an abattoir during an interval of 14 months were found contaminated with PPV. Because each lot was usually comprised of kidneys from 2 litters, the latter finding suggests that 3 of approximately 98 litters were infected. Prior infection of FPK cell cultures with PPV resulted in only slight interference of replication of other selected viruses; i.e., porcine enterovirus (PEV), pseudorabies virus (PRV), vesicular stomatitis virus (VSV), and hemagglutinating encephalomyelitis virus (HEV). Moreover, PPV and HEV were propagated in the same cell cultures during 5 serial passages of the viruses. In contrast, when copropagation of PPV and VSV was attempted, PPV was not detected after the 2nd serial passage.", "contents": "Porcine parvovirus: frequency of naturally occurring transplacental infection and viral contamination of fetal porcine kidney cell cultures. The frequency of naturally occurring transplacental infection of swine with porcine parvovirus (PPV) and one of the possible consequences of such infection--the presence of PPV in cell cultures prepared from fetal tissues--were investigated. Transplacental infection was indicated by the presence of high titers of hemagglutination inhibiting (HI) antibody for PPV in serums of 0-day-old, hysterectomy-derived, colostrum-deprived pigs of 3 of 82 litters. All letters were farm-raised dams. Moreover, cell cultures prepared from 3 of 49 lots of fetal porcine kidneys (FPK) collected from an abattoir during an interval of 14 months were found contaminated with PPV. Because each lot was usually comprised of kidneys from 2 litters, the latter finding suggests that 3 of approximately 98 litters were infected. Prior infection of FPK cell cultures with PPV resulted in only slight interference of replication of other selected viruses; i.e., porcine enterovirus (PEV), pseudorabies virus (PRV), vesicular stomatitis virus (VSV), and hemagglutinating encephalomyelitis virus (HEV). Moreover, PPV and HEV were propagated in the same cell cultures during 5 serial passages of the viruses. In contrast, when copropagation of PPV and VSV was attempted, PPV was not detected after the 2nd serial passage."} {"id": "PMID:163604", "title": "Immunogenic and protective effects of the F-2 strain of feline viral rhinotracheitis virus.", "content": "The F-2 strain of feline viral rhinotracheitis (FVE) virus was administered by intramuscular (IM) injection to susceptible cats. The cats developed serum-neutralizing antibodies and were protected to a significant degree when given, by intranasal (IN) instillation challenge inoculum of a virulent strain of FVR virus.", "contents": "Immunogenic and protective effects of the F-2 strain of feline viral rhinotracheitis virus. The F-2 strain of feline viral rhinotracheitis (FVE) virus was administered by intramuscular (IM) injection to susceptible cats. The cats developed serum-neutralizing antibodies and were protected to a significant degree when given, by intranasal (IN) instillation challenge inoculum of a virulent strain of FVR virus."} {"id": "PMID:163606", "title": "Broad-beta disease (type III hyperlipoproteinemia) in a large kindred. Evidence for a monogenic mechanism.", "content": "The inheritance of broad-beta disease (as specified by a type III lipoprotein pattern) has remained an enigma. Previous reports have variously implicated a single gene (autosomal dominant mode), a double dose of a single gene (autosomal recessive), two separate genes (mixed heterozygosity), or multiple genes (polygenic inheritance). The present study of a single, large kindred of 108 members spanning 4 generations provides evidence for an autosomal dominant mode, since at least 1 member of the first generation pair was normal, at least 5 of their 9 children had type III patterns, and at least 2 of these (whose spouses were normal) transmitted this pattern to their offspring. The findings also suggest that in this kindred the common occurrence of hypertriglyceridemia (in a type IV pattern) may represent either a variable phenotypic expression of the gene for broad-beta disease or the coexistence of a second, independent genetic lipid disorder.", "contents": "Broad-beta disease (type III hyperlipoproteinemia) in a large kindred. Evidence for a monogenic mechanism. The inheritance of broad-beta disease (as specified by a type III lipoprotein pattern) has remained an enigma. Previous reports have variously implicated a single gene (autosomal dominant mode), a double dose of a single gene (autosomal recessive), two separate genes (mixed heterozygosity), or multiple genes (polygenic inheritance). The present study of a single, large kindred of 108 members spanning 4 generations provides evidence for an autosomal dominant mode, since at least 1 member of the first generation pair was normal, at least 5 of their 9 children had type III patterns, and at least 2 of these (whose spouses were normal) transmitted this pattern to their offspring. The findings also suggest that in this kindred the common occurrence of hypertriglyceridemia (in a type IV pattern) may represent either a variable phenotypic expression of the gene for broad-beta disease or the coexistence of a second, independent genetic lipid disorder."} {"id": "PMID:163607", "title": "Type III hyperlipoproteinemia: an analysis of two contemporary definitions.", "content": "Two current definitions of type III hyperlipoproteinemia, \"floating beta\" lipoproteins and an estimate of the relative content of cholesterol and triglyceride in lipoproteins of density less than 1,006 (very low-density [VLD] lipoproteins), have been compared. Over 3100 complete lipoprotein analyses of 182 adults with primary familial hyperglyceridemia, covering a wide range of plasma lipid concentrations, formed the data base for this retrospective analysis: The ratio of VLD lipoprotein cholesterol to the plasma triglyceride concentration (VLDL/TG=r) proved capable of segregating an apparently unique subpopulation with persistently abnormal very low-density lipoprotein composition. Although floating beta lipoproteins were present in nearly all patients with a high r value, they also appeared inconsistently in many other patients. It is concluded that the chemical index to VLD lipoprotein composition is the better, albeit, temporary definition for this disorder. When the plasma triglyceride concentration is between 150 and 1000 mg/100 ml, an r not less than 0.25 should be considered as suggestive and a value not less than 0.30 as diagnosttc of type III hyperlipoproteinemia.", "contents": "Type III hyperlipoproteinemia: an analysis of two contemporary definitions. Two current definitions of type III hyperlipoproteinemia, \"floating beta\" lipoproteins and an estimate of the relative content of cholesterol and triglyceride in lipoproteins of density less than 1,006 (very low-density [VLD] lipoproteins), have been compared. Over 3100 complete lipoprotein analyses of 182 adults with primary familial hyperglyceridemia, covering a wide range of plasma lipid concentrations, formed the data base for this retrospective analysis: The ratio of VLD lipoprotein cholesterol to the plasma triglyceride concentration (VLDL/TG=r) proved capable of segregating an apparently unique subpopulation with persistently abnormal very low-density lipoprotein composition. Although floating beta lipoproteins were present in nearly all patients with a high r value, they also appeared inconsistently in many other patients. It is concluded that the chemical index to VLD lipoprotein composition is the better, albeit, temporary definition for this disorder. When the plasma triglyceride concentration is between 150 and 1000 mg/100 ml, an r not less than 0.25 should be considered as suggestive and a value not less than 0.30 as diagnosttc of type III hyperlipoproteinemia."} {"id": "PMID:163608", "title": "The biochemical, clinical, and genetic features of type III hyperlipoproteinemia.", "content": "The clinical and biochemical features of type III hyperlipoproteinemia are described in 49 patients from 23 to 70 years of age. An increase in very low-density lipoproteins (VLDL) of abnormal chemical composition was the basis for diagnosis. The untreated patients all had hypercholesterolemia and hyperglyceridemia, and, on the average, decreased concentrations of both low- and high-density lipoproteins. Seventy-four percent had xanthomas, and classic \"xanthoma striata palmaris\" was found in more than half. Twenty-seven percent had ischemic heart disease, detected earlier in men than in women. Twenty-seven percent had peripheral vascular disease (compared to 4% of subjects with type II hyperlipoproteinemia). Twenty-five of 35 subjects achieved normal lipid levels with dietary therapy alone. Analysis of 29 kindred showed hyperlipidemia in half of adult blood relatives; half of these had type III, the remainder usually had sample endogenous hyperglyceridemia (type IV). Only 2 of 55 children less than 20 years of age were affected, both with type IV.", "contents": "The biochemical, clinical, and genetic features of type III hyperlipoproteinemia. The clinical and biochemical features of type III hyperlipoproteinemia are described in 49 patients from 23 to 70 years of age. An increase in very low-density lipoproteins (VLDL) of abnormal chemical composition was the basis for diagnosis. The untreated patients all had hypercholesterolemia and hyperglyceridemia, and, on the average, decreased concentrations of both low- and high-density lipoproteins. Seventy-four percent had xanthomas, and classic \"xanthoma striata palmaris\" was found in more than half. Twenty-seven percent had ischemic heart disease, detected earlier in men than in women. Twenty-seven percent had peripheral vascular disease (compared to 4% of subjects with type II hyperlipoproteinemia). Twenty-five of 35 subjects achieved normal lipid levels with dietary therapy alone. Analysis of 29 kindred showed hyperlipidemia in half of adult blood relatives; half of these had type III, the remainder usually had sample endogenous hyperglyceridemia (type IV). Only 2 of 55 children less than 20 years of age were affected, both with type IV."} {"id": "PMID:163609", "title": "The lipid storage diseases: new concepts and control.", "content": "The nature of the enzymatic defect is now well established in ten inherited disorders of lipid metabolism. This information has provided for the development of facile, sensitive tests using readily available materials such as washed leukocytes or cultured skin fibroblasts for the diagnosis of these disorders; the detection of heterozygous carriers of these traits; and the monitoring of pregnancies at risk for any of these conditions. Recent investigations of enzyme replacement therapy have shown great promise for the treatment of patients with Fabry's disease and those with the adult form of Gaucher's disease. Additional procedures must be developed for successful enzyme replacement in patients where the central nervous system is damaged by the accumulation of lipids.", "contents": "The lipid storage diseases: new concepts and control. The nature of the enzymatic defect is now well established in ten inherited disorders of lipid metabolism. This information has provided for the development of facile, sensitive tests using readily available materials such as washed leukocytes or cultured skin fibroblasts for the diagnosis of these disorders; the detection of heterozygous carriers of these traits; and the monitoring of pregnancies at risk for any of these conditions. Recent investigations of enzyme replacement therapy have shown great promise for the treatment of patients with Fabry's disease and those with the adult form of Gaucher's disease. Additional procedures must be developed for successful enzyme replacement in patients where the central nervous system is damaged by the accumulation of lipids."} {"id": "PMID:163611", "title": "Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements.", "content": "Hypoglycemia coexisting with very low plasma immunoreactive insulin concentrations was found in a 78-year-old woman with an insulinoma. However, the absolute proinsulin levels during hypoglycemia were elevated (0.9 to 1.4 ng/ml), accounting for 66.5% of the total circulating immunoreactive insulinlike material. The raised serum proinsulin concentrations together with an abnormal proinsulin:insulin ratio proved to be of critical importance in establishing the diagnosis of an islet-cell tumor in this patient.", "contents": "Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements. Hypoglycemia coexisting with very low plasma immunoreactive insulin concentrations was found in a 78-year-old woman with an insulinoma. However, the absolute proinsulin levels during hypoglycemia were elevated (0.9 to 1.4 ng/ml), accounting for 66.5% of the total circulating immunoreactive insulinlike material. The raised serum proinsulin concentrations together with an abnormal proinsulin:insulin ratio proved to be of critical importance in establishing the diagnosis of an islet-cell tumor in this patient."} {"id": "PMID:163614", "title": "Collagenolytic activity of some marine bacteria.", "content": "Reconstituted, acid-extracted collagen was used to prepare a medium to screen proteolytic marine bacteria for their ability to elaborate collagenolytic enzymes. The medium was resistant to solubilization by trypsin, hyaluronidase, chondroitinase ABC, and various marine proteinases, but was readily hydrolyzed by commercial Clostridium collagenases. Eighty-seven marine isolates collected in the vicinity of Bermuda, Oahu (Hawaii), and Stone Harbor and Cape May, N. J., were screened. Approximately 44 per cent of the isolates were capable of elaborating enzymes that hydrolyzed reconstituted collagen gels. Several cultures produced collagenolytic enzymes only when grown in the presence of collagen or degradation products of collagen, and with very few exceptions the presence of collagen in the medium greatly enhanced collagenolytic enzyme production. The enzymes from a collagenolytic Bermuda marine isolate were studied in more detail to illustrate that the enzymes capable of hydrolyzing reconstituted collagen were separable from nonspecific proteinases by zone electrophoresis and that these enzymes were true collagenases by virtue of their ability to hydrolyze native bovine Achilles'tendon obtained from three different sources.", "contents": "Collagenolytic activity of some marine bacteria. Reconstituted, acid-extracted collagen was used to prepare a medium to screen proteolytic marine bacteria for their ability to elaborate collagenolytic enzymes. The medium was resistant to solubilization by trypsin, hyaluronidase, chondroitinase ABC, and various marine proteinases, but was readily hydrolyzed by commercial Clostridium collagenases. Eighty-seven marine isolates collected in the vicinity of Bermuda, Oahu (Hawaii), and Stone Harbor and Cape May, N. J., were screened. Approximately 44 per cent of the isolates were capable of elaborating enzymes that hydrolyzed reconstituted collagen gels. Several cultures produced collagenolytic enzymes only when grown in the presence of collagen or degradation products of collagen, and with very few exceptions the presence of collagen in the medium greatly enhanced collagenolytic enzyme production. The enzymes from a collagenolytic Bermuda marine isolate were studied in more detail to illustrate that the enzymes capable of hydrolyzing reconstituted collagen were separable from nonspecific proteinases by zone electrophoresis and that these enzymes were true collagenases by virtue of their ability to hydrolyze native bovine Achilles'tendon obtained from three different sources."} {"id": "PMID:163615", "title": "Uptake and elimination of poliovirus by West Coast oysters.", "content": "Accumulation of poliovirus Lsc-2ab by West Coast oysters was determined by using a stationary seawater system, and depuration was determined by using both stationary and free-flow systems. Results indicate that these shellfish have the same pattern of accumulation and localization of viruses as do East Coast species. However, uptake appeared to occur more rapidly than described for East Coast shellfish. There appeared to be a gradual diffusion of virus from the digestive area into the body. Depuration was found to occur more rapidly and completely under free-flow conditions than in a stationary system.", "contents": "Uptake and elimination of poliovirus by West Coast oysters. Accumulation of poliovirus Lsc-2ab by West Coast oysters was determined by using a stationary seawater system, and depuration was determined by using both stationary and free-flow systems. Results indicate that these shellfish have the same pattern of accumulation and localization of viruses as do East Coast species. However, uptake appeared to occur more rapidly than described for East Coast shellfish. There appeared to be a gradual diffusion of virus from the digestive area into the body. Depuration was found to occur more rapidly and completely under free-flow conditions than in a stationary system."} {"id": "PMID:163616", "title": "Inactivation of viruses and bacteria by ozone, with and without sonication.", "content": "Selected organisms with public health significance were placed in a reaction chamber for treatment by ozonation, by ozonation and sonication, by sonication, or by sonication during oxygenation. Vesicular stomatitis virus, encephalomyocarditis virus, GDVII virus, Staphylococcus aureus, Pseudomonas fluorescens, Salmonella typhimurium, enteropathogenic Escherichia coli, Vibrio cholerae, and Shigella flexneri were inactivated by treatment with ozone. When microorganisms were suspended in phosphate-buffered saline, they were inactivated rapidly by treatment with ozone. However, microorganisms suspended in secondary effluent from a wastewater treatment plant required longer contact times with ozone for complete inactivation. Simultaneous treatments by ozonation and sonication reduced the contact time for complete inactivation of microorganisms in secondary effluent. Treatment by sonication alone or sonication and oxygenation did not inactivate microorganisms. Therefore, the simultaneous treatment of microorganisms in secondary effluent with ozone and sonication resulted in a synergistic effect.", "contents": "Inactivation of viruses and bacteria by ozone, with and without sonication. Selected organisms with public health significance were placed in a reaction chamber for treatment by ozonation, by ozonation and sonication, by sonication, or by sonication during oxygenation. Vesicular stomatitis virus, encephalomyocarditis virus, GDVII virus, Staphylococcus aureus, Pseudomonas fluorescens, Salmonella typhimurium, enteropathogenic Escherichia coli, Vibrio cholerae, and Shigella flexneri were inactivated by treatment with ozone. When microorganisms were suspended in phosphate-buffered saline, they were inactivated rapidly by treatment with ozone. However, microorganisms suspended in secondary effluent from a wastewater treatment plant required longer contact times with ozone for complete inactivation. Simultaneous treatments by ozonation and sonication reduced the contact time for complete inactivation of microorganisms in secondary effluent. Treatment by sonication alone or sonication and oxygenation did not inactivate microorganisms. Therefore, the simultaneous treatment of microorganisms in secondary effluent with ozone and sonication resulted in a synergistic effect."} {"id": "PMID:163617", "title": "Influence of carbohydrates on growth and sporulation of Clostridium perfringens type A.", "content": "Growth and sporulation of Clostridium perfringens type A in Duncan and Strong (DS) sporulation medium was investigated. A biphasic growth response was found to be dependent on starch concentration. Maximal levels of heat-resistant spores were formed at a starch concentration of 0.40%. Addition of glucose, maltose, or maltotriose to a sporulating culture resulted in an immediate turbidity increase, indicating that biphasic growth in DS medium may be due to such starch degradation products. Amylose and, to a lesser extent, amylopectin resulted in biphasic growth when each replaced starch in the sporulation medium. A levels of heat-resistant spores approximately equal to the control was produced with amylopectin but not amylose as the added carbohydrate. Addition of glucose or maltose to a DS medium without starch at stage II or III of sporulation did not alter the level of heat-resistant spores as compared with the level obtained in DS medium with starch. Omission of starch or glucose or maltose resulted in an approximately 100-fold decrease in the number of heat-resistant spores, although the percentage of sporulation (90%) was unaffected. The role of starch and amylopectin in the formation of heat-resistant spores probably involves the amyloytic production of utilizable short-chain glucose polymers that provide an energy source for the completion of sporulation.", "contents": "Influence of carbohydrates on growth and sporulation of Clostridium perfringens type A. Growth and sporulation of Clostridium perfringens type A in Duncan and Strong (DS) sporulation medium was investigated. A biphasic growth response was found to be dependent on starch concentration. Maximal levels of heat-resistant spores were formed at a starch concentration of 0.40%. Addition of glucose, maltose, or maltotriose to a sporulating culture resulted in an immediate turbidity increase, indicating that biphasic growth in DS medium may be due to such starch degradation products. Amylose and, to a lesser extent, amylopectin resulted in biphasic growth when each replaced starch in the sporulation medium. A levels of heat-resistant spores approximately equal to the control was produced with amylopectin but not amylose as the added carbohydrate. Addition of glucose or maltose to a DS medium without starch at stage II or III of sporulation did not alter the level of heat-resistant spores as compared with the level obtained in DS medium with starch. Omission of starch or glucose or maltose resulted in an approximately 100-fold decrease in the number of heat-resistant spores, although the percentage of sporulation (90%) was unaffected. The role of starch and amylopectin in the formation of heat-resistant spores probably involves the amyloytic production of utilizable short-chain glucose polymers that provide an energy source for the completion of sporulation."} {"id": "PMID:163618", "title": "Bacterial metabolism of arylsulfonates: role of meta cleavage in benzene sulfonate oxidation by Pseudomonas testosteroni.", "content": "Pseudomonas testosteroni H-8 oxidizes certain lower alkylbenzene sulfonates at rates inversely related to the length of the alkyl group. Appreciable Q(O)2 values were observed for benzene sulfonate (BS), toluene sulfonate (TS), and ethylbenzene sulfonate (EBS), but not for propylbenzene sulfonate (PS) and higher homologues. Catechol oxidation was catalyzed by a constitutive catechol-2,3-oxygenase (EC 1.99.2.a). Yellow meta cleavage products accumulated when BS-grown cells were exposed to catechol, 4-methylcatechol, 3-methylcatechol, EBS and PS, but not BS or TS. Traces of a yellow metabolite (probably 2-hydroxymuconic semialdehyde) were detectable during growth on BS. PS completely inhibited growth on BS, but not on L-leucine or nutrient broth. Also, PS antagonized respiration on BS and catechol, but not glutamate, the extent of inhibition being directly related to PS concentration. Formation of a meta cleavage product from PS, and inhibition of catechol oxidation by PS, suggested that the actual inhibitor may not be PS itself, but a metabolite.", "contents": "Bacterial metabolism of arylsulfonates: role of meta cleavage in benzene sulfonate oxidation by Pseudomonas testosteroni. Pseudomonas testosteroni H-8 oxidizes certain lower alkylbenzene sulfonates at rates inversely related to the length of the alkyl group. Appreciable Q(O)2 values were observed for benzene sulfonate (BS), toluene sulfonate (TS), and ethylbenzene sulfonate (EBS), but not for propylbenzene sulfonate (PS) and higher homologues. Catechol oxidation was catalyzed by a constitutive catechol-2,3-oxygenase (EC 1.99.2.a). Yellow meta cleavage products accumulated when BS-grown cells were exposed to catechol, 4-methylcatechol, 3-methylcatechol, EBS and PS, but not BS or TS. Traces of a yellow metabolite (probably 2-hydroxymuconic semialdehyde) were detectable during growth on BS. PS completely inhibited growth on BS, but not on L-leucine or nutrient broth. Also, PS antagonized respiration on BS and catechol, but not glutamate, the extent of inhibition being directly related to PS concentration. Formation of a meta cleavage product from PS, and inhibition of catechol oxidation by PS, suggested that the actual inhibitor may not be PS itself, but a metabolite."} {"id": "PMID:163619", "title": "Mummified cutaneous mixed tumor.", "content": "A 34-year-old man had an unusual mummified cutaneous mixed tumor that developed shortly after trauma. The apocrine type of tumor cells and pilar differentiation could explain the presence of mummification.", "contents": "Mummified cutaneous mixed tumor. A 34-year-old man had an unusual mummified cutaneous mixed tumor that developed shortly after trauma. The apocrine type of tumor cells and pilar differentiation could explain the presence of mummification."} {"id": "PMID:163621", "title": "Intracavitary cardiac extension of hepatoma.", "content": "Acute right atrial obstruction in a 62-year-old man was demonstrated angiographically to be due to a tumor, which was later proved to be metastatic hepatoma. Resection of the tumor resulted in total symptomatic relief.", "contents": "Intracavitary cardiac extension of hepatoma. Acute right atrial obstruction in a 62-year-old man was demonstrated angiographically to be due to a tumor, which was later proved to be metastatic hepatoma. Resection of the tumor resulted in total symptomatic relief."} {"id": "PMID:163622", "title": "Effects of diazepam on photosynthesis, respiration, rubidium uptake, and finestructure of Scenedesmus obliquus in synchronous cultures.", "content": "Effects of diazepam (Valium) on photosynthesis, chlorophyll/photosynthesis ratios, respiration, uptake of rubidium ions, and ultrastructure of Scenedesmus obliquus synchronized by a light-dark regimen of 14:10 hrs were determined. 80 and 160 muM diazepam, added to the nutrient medium at the start of the light-dark change (i.e., start of the cell cycle) gradually reduced rates of photosynthesis, below the initial rates from the beginning of the experiment. Contents of chlorophyll, however, remained nearly unaffected. Consequently, the diazepam-treated cells had a higher chlorophyll/photosynthesis ratio--also with regard to respiration in order to calculate the gross photosynthesis. The occurrence of photorespiration cannot be assumed. The net influx of rubidium was slightly reduced by 100 muM diazepam 0.5 and 2.0 hrs after the start of the cell cycle and was strongly inhibited after 5 to 14 hrs. 80 and 160 muM diazepam caused separation of thylakoids, formation of giant mitochondria and enlargement of vacuoles.", "contents": "Effects of diazepam on photosynthesis, respiration, rubidium uptake, and finestructure of Scenedesmus obliquus in synchronous cultures. Effects of diazepam (Valium) on photosynthesis, chlorophyll/photosynthesis ratios, respiration, uptake of rubidium ions, and ultrastructure of Scenedesmus obliquus synchronized by a light-dark regimen of 14:10 hrs were determined. 80 and 160 muM diazepam, added to the nutrient medium at the start of the light-dark change (i.e., start of the cell cycle) gradually reduced rates of photosynthesis, below the initial rates from the beginning of the experiment. Contents of chlorophyll, however, remained nearly unaffected. Consequently, the diazepam-treated cells had a higher chlorophyll/photosynthesis ratio--also with regard to respiration in order to calculate the gross photosynthesis. The occurrence of photorespiration cannot be assumed. The net influx of rubidium was slightly reduced by 100 muM diazepam 0.5 and 2.0 hrs after the start of the cell cycle and was strongly inhibited after 5 to 14 hrs. 80 and 160 muM diazepam caused separation of thylakoids, formation of giant mitochondria and enlargement of vacuoles."} {"id": "PMID:163623", "title": "Ultrastructural changes occurring during germination and outgrowth of spores of the thermophile Bacillus acidocaldarius.", "content": "Spores of the thermophilic, acidophilic, Bacillus acidocaldarius were covered by a thick outer coat and a laminated inner coat (5.5 nm periodicity). Small membranous vesicles were present in the spore core and they disappeared as germination proceeded. After depolymerization of the cortex, and a 30% increase in spore diameter a localized gap appeared in the laminated inner coat only. This inner coat gap was narrow and could be the whole length of the spore. The germ cell appeared to grow, or to be pushed towards the inner coat gap, at which stage the outer coat disappeared in the same localized area. As the vegetative cell grew out the spore coat fell away, with loose cortical material still attached to it. The young germ cell developed a large spherical electron dense inclusion body in the cytoplasm, at the same time as the ribosomal and nuclear areas became distinct.", "contents": "Ultrastructural changes occurring during germination and outgrowth of spores of the thermophile Bacillus acidocaldarius. Spores of the thermophilic, acidophilic, Bacillus acidocaldarius were covered by a thick outer coat and a laminated inner coat (5.5 nm periodicity). Small membranous vesicles were present in the spore core and they disappeared as germination proceeded. After depolymerization of the cortex, and a 30% increase in spore diameter a localized gap appeared in the laminated inner coat only. This inner coat gap was narrow and could be the whole length of the spore. The germ cell appeared to grow, or to be pushed towards the inner coat gap, at which stage the outer coat disappeared in the same localized area. As the vegetative cell grew out the spore coat fell away, with loose cortical material still attached to it. The young germ cell developed a large spherical electron dense inclusion body in the cytoplasm, at the same time as the ribosomal and nuclear areas became distinct."} {"id": "PMID:163624", "title": "Microbial assimilation of hydrocarbons. I. The fine-structure of a hydrocarbon oxidizing Acinetobacter sp.", "content": "1. The fine-structure analysis of the hydrocarbon oxidizing microorganism, Acinetobacter sp., demonstrated a cytoplasmic modification resulting from growth on paraffinic and olefinic hydrocarbons. 2. Intracytoplasmic hydrocarbon inclusions were documented by electron microscopy with chemical identifications obtained by gas chromatography and X-ray diffraction. 3. These results demonstrate the ability of a microorganism to accumulate hydrocarbon substrates intracellularly which, in turn, indicates the transport across the cell membrane.", "contents": "Microbial assimilation of hydrocarbons. I. The fine-structure of a hydrocarbon oxidizing Acinetobacter sp. 1. The fine-structure analysis of the hydrocarbon oxidizing microorganism, Acinetobacter sp., demonstrated a cytoplasmic modification resulting from growth on paraffinic and olefinic hydrocarbons. 2. Intracytoplasmic hydrocarbon inclusions were documented by electron microscopy with chemical identifications obtained by gas chromatography and X-ray diffraction. 3. These results demonstrate the ability of a microorganism to accumulate hydrocarbon substrates intracellularly which, in turn, indicates the transport across the cell membrane."} {"id": "PMID:163625", "title": "Duration of hospitalization for alcoholism.", "content": "On admission to an inpatient alcoholic treatment center, 58 alcoholic men were randomly assigned to two groups. One group was detoxified and after-care services were planned (mean length of stay nine days). The other group, in a-dition to the above, received intensive psychosocial inhospital treatment (mean length of stay 30 days). Posthospital adjustment was measured at five intervals over a 13 month period in the areas of social relationships, financial status, employment record, legal involvement, drinking behavior, use of measures were obtained on psychological change and counseling readiness. No significant difference was found between the two groups on any measure. These results indicate that the hospital has a limited role in the treatment of the alcholic person.", "contents": "Duration of hospitalization for alcoholism. On admission to an inpatient alcoholic treatment center, 58 alcoholic men were randomly assigned to two groups. One group was detoxified and after-care services were planned (mean length of stay nine days). The other group, in a-dition to the above, received intensive psychosocial inhospital treatment (mean length of stay 30 days). Posthospital adjustment was measured at five intervals over a 13 month period in the areas of social relationships, financial status, employment record, legal involvement, drinking behavior, use of measures were obtained on psychological change and counseling readiness. No significant difference was found between the two groups on any measure. These results indicate that the hospital has a limited role in the treatment of the alcholic person."} {"id": "PMID:163626", "title": "Reflex patters initiated by the secondary sensory fiber endings of muscle spindles: a proposal.", "content": "Muscle spindles have two kinds of sensory fibers, each with stretch-sensitive endings on the nuclear bag muscle fibers and the nuclear chain muscle fibers within the spindle. The stretch reflex responses initiated by the primary sensory fibers have been well defines. There are other stretch reflexes of poorly defined origin and distribution. Clinical studies on spastic patients indicate that these stretch reflexes show regional responses or regional synergies. Stretch of flexor muscles of proximal joints of an extremity causes slowly recruiting, prolonged, reflex flexion in that extremity, in the contralateral extremity and also in the ipsilateral extremity, producing the crossed extension-flexion reflex and long spinal reflex. Likewise, stretch of extensor muscles of the proximal joints initiates a similar extension reflex in the same distribution. Stretch of the distal flexors of an extremity reflexly spreads flexion through that extremity. Stretch of the distal extensors of an extremity spreads extension throughout that extremity. These reflexes can be abolished by intramuscular neurolysis with phenol. They have long internuncial pathways and involve both alpha and gamma motoneurons. The demonstration that these reflex patterns are initiated by stretch of the muscle and show characteristics similar to those shown in physiological studies by the secondary sensory spindle reflexes suggests that they are initiated by stretch of the endings of the secondary sensory fibers of muscle spindles.", "contents": "Reflex patters initiated by the secondary sensory fiber endings of muscle spindles: a proposal. Muscle spindles have two kinds of sensory fibers, each with stretch-sensitive endings on the nuclear bag muscle fibers and the nuclear chain muscle fibers within the spindle. The stretch reflex responses initiated by the primary sensory fibers have been well defines. There are other stretch reflexes of poorly defined origin and distribution. Clinical studies on spastic patients indicate that these stretch reflexes show regional responses or regional synergies. Stretch of flexor muscles of proximal joints of an extremity causes slowly recruiting, prolonged, reflex flexion in that extremity, in the contralateral extremity and also in the ipsilateral extremity, producing the crossed extension-flexion reflex and long spinal reflex. Likewise, stretch of extensor muscles of the proximal joints initiates a similar extension reflex in the same distribution. Stretch of the distal flexors of an extremity reflexly spreads flexion through that extremity. Stretch of the distal extensors of an extremity spreads extension throughout that extremity. These reflexes can be abolished by intramuscular neurolysis with phenol. They have long internuncial pathways and involve both alpha and gamma motoneurons. The demonstration that these reflex patterns are initiated by stretch of the muscle and show characteristics similar to those shown in physiological studies by the secondary sensory spindle reflexes suggests that they are initiated by stretch of the endings of the secondary sensory fibers of muscle spindles."} {"id": "PMID:163627", "title": "Pediatric cadaver kidneys. Their use in renal transplantation.", "content": "Of 350 consecutive cadaver kidney transplants, 32 kidneys from donors aged 1 day to 9 years were transplanted. Our results indicate that, with strict adherence to certain guidelines in kidney procurement and transplantion, pediatric kidneys are excellent donor graft material. In contrast to en bloc transplantation of both kidneys from pediatric donors, each donor can provide kidneys for two recipients. In addition, the transplantation of pediatric kidneys as single units is both simple and safe.", "contents": "Pediatric cadaver kidneys. Their use in renal transplantation. Of 350 consecutive cadaver kidney transplants, 32 kidneys from donors aged 1 day to 9 years were transplanted. Our results indicate that, with strict adherence to certain guidelines in kidney procurement and transplantion, pediatric kidneys are excellent donor graft material. In contrast to en bloc transplantation of both kidneys from pediatric donors, each donor can provide kidneys for two recipients. In addition, the transplantation of pediatric kidneys as single units is both simple and safe."} {"id": "PMID:163628", "title": "Histocompatibility antigens and solid malignant neoplasms.", "content": "To evaluate the relation between histocompatibility antigen phenotypes and solid malignant neoplasms, HL-A type was determined in 633 cancer patients and compared with those of 489 normal controls. HL-A8 was elevated in patients with squamous cancer, melanoma, and adenocarcinoma. The highest incidence occurred in patients with salivary gland adenocarcinoma (67% vs only 17% in normal controls). A threefold increase in HL-A5 was detected in patients with connective tissue sarcomas (28% incidence vs 9% in normal controls). Antigen frequencies did not vary when analyzed by time of diagnosis or interval after treatment. The finding that certain malignant neoplasms have associations with increased frequency of individual HL-A antigens may give clues to cause and genesis for these tumors.", "contents": "Histocompatibility antigens and solid malignant neoplasms. To evaluate the relation between histocompatibility antigen phenotypes and solid malignant neoplasms, HL-A type was determined in 633 cancer patients and compared with those of 489 normal controls. HL-A8 was elevated in patients with squamous cancer, melanoma, and adenocarcinoma. The highest incidence occurred in patients with salivary gland adenocarcinoma (67% vs only 17% in normal controls). A threefold increase in HL-A5 was detected in patients with connective tissue sarcomas (28% incidence vs 9% in normal controls). Antigen frequencies did not vary when analyzed by time of diagnosis or interval after treatment. The finding that certain malignant neoplasms have associations with increased frequency of individual HL-A antigens may give clues to cause and genesis for these tumors."} {"id": "PMID:163629", "title": "Cyclic AMP response to epinephrine and shock.", "content": "Hormonal regulation is fundamental to homeostasis, and the response in tissues is mediated by adenosine 3':5' equals cyclic phosphate (cyclic AMP). Since circulating levels of catecholamines are elevated during hemorrhagic shock, experiments were carried out to study the effects of epinephrine and of shock on cyclic AMP levels of plasma and of the intestine, a particularly vulnerable organ in canine hemorrhagic shock. Epinephrine was given to normotensive dogs as a constant infusion (group 1) or as a single pulse (group 2). Sequential blood samples showed a marked increase in circulating cyclic AMP, especially in portal and hepatic venous blood. Little change was noted in the tissues. Hemorrhagic shock (group 3) induced a marked increase in plasma cyclic AMP, with a depletion of mucosal cyclic AMP and adenosine triphosphate (ATP). Pretreatment before shock with alpha-blockade (group 4) abolished the decrease in mucosal cyclic AMP and ATP, and reduced the increase in plasma cyclic AMP.", "contents": "Cyclic AMP response to epinephrine and shock. Hormonal regulation is fundamental to homeostasis, and the response in tissues is mediated by adenosine 3':5' equals cyclic phosphate (cyclic AMP). Since circulating levels of catecholamines are elevated during hemorrhagic shock, experiments were carried out to study the effects of epinephrine and of shock on cyclic AMP levels of plasma and of the intestine, a particularly vulnerable organ in canine hemorrhagic shock. Epinephrine was given to normotensive dogs as a constant infusion (group 1) or as a single pulse (group 2). Sequential blood samples showed a marked increase in circulating cyclic AMP, especially in portal and hepatic venous blood. Little change was noted in the tissues. Hemorrhagic shock (group 3) induced a marked increase in plasma cyclic AMP, with a depletion of mucosal cyclic AMP and adenosine triphosphate (ATP). Pretreatment before shock with alpha-blockade (group 4) abolished the decrease in mucosal cyclic AMP and ATP, and reduced the increase in plasma cyclic AMP."} {"id": "PMID:163630", "title": "Mouse hepatitis virus-induced recurrent demyelination. A preliminary report.", "content": "Four-week-old BALB/c mice inoculated intracerebrally with the JHM strain of mouse hepatitis virus developed an acute demyelinating disease followed by apparent recovery with remyelination. When surviving mice were examined 16 months later, small areas of active demyelination were still present. This is the first reported example, to our knowledge, of an experimental viral infection in which acute demyelination with recovery is followed by persisting or recurring demyelination.", "contents": "Mouse hepatitis virus-induced recurrent demyelination. A preliminary report. Four-week-old BALB/c mice inoculated intracerebrally with the JHM strain of mouse hepatitis virus developed an acute demyelinating disease followed by apparent recovery with remyelination. When surviving mice were examined 16 months later, small areas of active demyelination were still present. This is the first reported example, to our knowledge, of an experimental viral infection in which acute demyelination with recovery is followed by persisting or recurring demyelination."} {"id": "PMID:163631", "title": "Hereditary hemorrhagic telangiectasia. A case with hepatocellular carcinoma and acquired hepatocerebral degeneration.", "content": "A patient with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), treated with ethinyl estradiol, multiple blood transfusions, and iron-dextran, developed hepatocellular carcinoma and acquired hepatocerebral degeneration. In addition to the carcinoma, the liver contained extensive arteriovenous maliformations, telangiectasis, and changes of Osler atypical cirrhosis. The carcinoma possibly had its genesis in the presence of an ocongenic serum hepatitis virus, or the cirrhosis, or both.", "contents": "Hereditary hemorrhagic telangiectasia. A case with hepatocellular carcinoma and acquired hepatocerebral degeneration. A patient with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), treated with ethinyl estradiol, multiple blood transfusions, and iron-dextran, developed hepatocellular carcinoma and acquired hepatocerebral degeneration. In addition to the carcinoma, the liver contained extensive arteriovenous maliformations, telangiectasis, and changes of Osler atypical cirrhosis. The carcinoma possibly had its genesis in the presence of an ocongenic serum hepatitis virus, or the cirrhosis, or both."} {"id": "PMID:163632", "title": "Lipoprotein receptors, cholesterol metabolism, and atherosclerosis.", "content": "Deposition of cholesterol esters in the arterial intima is a characteristic feature of human atherosclerosis. Very little is known about the mechanisms by which cells normally regulate their cholesterol ester content. Recent studies in cultured human cells demonstrate the existence of a cell surface receptor that binds plasma low density lipoproteins and regulates the sterol content of cells by modulating the rates of uptake, esterification, and synthesis of cholesterol. A possible role for this lipoprotein receptor in the pathogenesis of atherosclerosis is discussed.", "contents": "Lipoprotein receptors, cholesterol metabolism, and atherosclerosis. Deposition of cholesterol esters in the arterial intima is a characteristic feature of human atherosclerosis. Very little is known about the mechanisms by which cells normally regulate their cholesterol ester content. Recent studies in cultured human cells demonstrate the existence of a cell surface receptor that binds plasma low density lipoproteins and regulates the sterol content of cells by modulating the rates of uptake, esterification, and synthesis of cholesterol. A possible role for this lipoprotein receptor in the pathogenesis of atherosclerosis is discussed."} {"id": "PMID:163633", "title": "Islet cell carcinoma of the pancreas.", "content": "Thirty cases of islet cell carcinoma of the pancreas diagnosed at Memorial Hospital were studied. There were 17 male and 13 female patients. The average age was 44 years. Most of the tumors were located in the body or tail of pancreas; in 25 instances, the primary tumor was larger than 6 cm. Epigastric pain, hypoglycemia, and jaundice were frequent primary clinical presentations. No morphological differences were found between functioning and nonfunctioning tumors. Size of tumor, local tissue infiltration, and vascular invasion were helpful; but they were not absolute parameters aiding in the differentiation of benign and malignant tumors. Twenty-six patients had metastatic disease at time of diagnosis. Liver, regional lymph nodes, bones, and peritoneum were common sites of metastases. The average survival was 3.9 years. The cumulative five-year survival rate was 65%.", "contents": "Islet cell carcinoma of the pancreas. Thirty cases of islet cell carcinoma of the pancreas diagnosed at Memorial Hospital were studied. There were 17 male and 13 female patients. The average age was 44 years. Most of the tumors were located in the body or tail of pancreas; in 25 instances, the primary tumor was larger than 6 cm. Epigastric pain, hypoglycemia, and jaundice were frequent primary clinical presentations. No morphological differences were found between functioning and nonfunctioning tumors. Size of tumor, local tissue infiltration, and vascular invasion were helpful; but they were not absolute parameters aiding in the differentiation of benign and malignant tumors. Twenty-six patients had metastatic disease at time of diagnosis. Liver, regional lymph nodes, bones, and peritoneum were common sites of metastases. The average survival was 3.9 years. The cumulative five-year survival rate was 65%."} {"id": "PMID:163634", "title": "Adrenocortical activity and urinary cyclic AMP levels: effects of hypobaric hypoxia.", "content": "Six highly motivated and trained military test subjects were exposed to a simulated altitude of 4267 m (477 torr) for 48 hours, prededed and followed by sea level runs lasting 32 hours. During each scenario tests subjects were required to perform their respective military tasks on a continual basis with sporadic rest not exceeding several hours. Extremely high levels of plasma cortisol prior to the start of each session and persistently elevated concentrations of urinary 17-OH corticosteroids at sea level were consistently observed. (This observation probably explains the relatively minor changes in adrenocortical output noted during acute exposure to hypobaric hypoxia. Analogous results were obtained for urinary cyclic AMP, i.e. elevated baseline levels and minimal response to high altitude. The results indicate an attenuated response as well as an association between urinary measures of adrenocortical activity and cyclic AMP excretion.", "contents": "Adrenocortical activity and urinary cyclic AMP levels: effects of hypobaric hypoxia. Six highly motivated and trained military test subjects were exposed to a simulated altitude of 4267 m (477 torr) for 48 hours, prededed and followed by sea level runs lasting 32 hours. During each scenario tests subjects were required to perform their respective military tasks on a continual basis with sporadic rest not exceeding several hours. Extremely high levels of plasma cortisol prior to the start of each session and persistently elevated concentrations of urinary 17-OH corticosteroids at sea level were consistently observed. (This observation probably explains the relatively minor changes in adrenocortical output noted during acute exposure to hypobaric hypoxia. Analogous results were obtained for urinary cyclic AMP, i.e. elevated baseline levels and minimal response to high altitude. The results indicate an attenuated response as well as an association between urinary measures of adrenocortical activity and cyclic AMP excretion."} {"id": "PMID:163635", "title": "Absence of nyctohemeral variation in stress-induced ACTH secretion in the rat.", "content": "Changes in plasma ACTH concentrations were measured in the adult male rat following a stressor in order to ascertain if there is a nyctohemeral variation in ACTH secretion following stress. The immuno-reactive ACTH concentrations obtained following a 2.5-min hind-leg tourniquet at 0400 or 1600 hours in pentobarbital-anesthetized animals were compared to those obtained in anesthetized and unanesthetized, unstressed controls. Neither absolute nor increment change in plasma ACTH concentrations following morning or afternoon tourniquet stress were significantly different after either 20 or 40 min anesthesia. Moreover, plasma ACTH concentrations from unstressed, unanesthetized rats showed a slight but significant difference (p smaller than 0.05) at 0400 hours [118 plus or minus 18 pg/ml (mean plus or minus SE)] compared to 1600 hours (64 plus or minus 12 pg/ml) indicating a reversal of the expected ACTH rhythm. Plasma corticosterone concentrations in these same rats showed the predicted lower-morning and higher-afternoon corticosterone pattern suggesting a possible nyctohemeral difference in the adrenal sensitivity to circulating levels of ACTH.", "contents": "Absence of nyctohemeral variation in stress-induced ACTH secretion in the rat. Changes in plasma ACTH concentrations were measured in the adult male rat following a stressor in order to ascertain if there is a nyctohemeral variation in ACTH secretion following stress. The immuno-reactive ACTH concentrations obtained following a 2.5-min hind-leg tourniquet at 0400 or 1600 hours in pentobarbital-anesthetized animals were compared to those obtained in anesthetized and unanesthetized, unstressed controls. Neither absolute nor increment change in plasma ACTH concentrations following morning or afternoon tourniquet stress were significantly different after either 20 or 40 min anesthesia. Moreover, plasma ACTH concentrations from unstressed, unanesthetized rats showed a slight but significant difference (p smaller than 0.05) at 0400 hours [118 plus or minus 18 pg/ml (mean plus or minus SE)] compared to 1600 hours (64 plus or minus 12 pg/ml) indicating a reversal of the expected ACTH rhythm. Plasma corticosterone concentrations in these same rats showed the predicted lower-morning and higher-afternoon corticosterone pattern suggesting a possible nyctohemeral difference in the adrenal sensitivity to circulating levels of ACTH."} {"id": "PMID:163640", "title": "The use of three dye-binding procedures for the assessment of heat damage to food proteins.", "content": "1. A study has been made of pure proteins heated either alone or in contact with sugars, so as to cause a severe fall in their reactive lysine contents, and also of commercial protein concentrations. 2. For unheated materials, and for bovine plasma albumin and fat-extracted, dried chicken muscle severely heated in the absence of sugar, Acid Orange 12 binding values (mmol bound dye/kg crude protein (nitrogen times 6-25)) were close to the sum of total histidine, total arginine and reactive lysine contents (mmol/kg crude protein (N times 6-25)), which we have termed HARL values. The dye-binding values and the HARL values were reduced similarly by heat treatment. 3. For materials in which protein and glucose had reacted under mild conditions (37 degrees), the dye-binding capacity with Acid Orange 12 was unchanged even though the HARL value of these materials was considerably reduced. When protein and glucose or sucrose were heated more severely, the dye-binding capacity was slightly lowered but not to the same extent as the reduction in the basic amino acids. 4. Animal feeding-stuffs, whether unheated, industrially processed or diliberately heated, appeared to react with Acid Orange 12 in the same way as the model systems (selected to represent three types of heat damage: 'advanced' and 'early' Maillard and protein-protein damage). 5. Remazol blue binding values and fluorodinitrobenzene (RDNB)-reactive lysine values were similarly reduced in materials that had been severely heated, either with or without added sugars; however, when protein and glucose had reacted under mild conditions the fall in Remazol blue binding was less than that in FDNB-reactive lysine. 6. For the model materials, binding with cresol red was, in general, higher for heated samples but the results showed no correlation with FDNB-reactive lysine values. For meat and groundnut meals, changes in values after heat treatment were smaller than those that have been reported for soya-bean meals.", "contents": "The use of three dye-binding procedures for the assessment of heat damage to food proteins. 1. A study has been made of pure proteins heated either alone or in contact with sugars, so as to cause a severe fall in their reactive lysine contents, and also of commercial protein concentrations. 2. For unheated materials, and for bovine plasma albumin and fat-extracted, dried chicken muscle severely heated in the absence of sugar, Acid Orange 12 binding values (mmol bound dye/kg crude protein (nitrogen times 6-25)) were close to the sum of total histidine, total arginine and reactive lysine contents (mmol/kg crude protein (N times 6-25)), which we have termed HARL values. The dye-binding values and the HARL values were reduced similarly by heat treatment. 3. For materials in which protein and glucose had reacted under mild conditions (37 degrees), the dye-binding capacity with Acid Orange 12 was unchanged even though the HARL value of these materials was considerably reduced. When protein and glucose or sucrose were heated more severely, the dye-binding capacity was slightly lowered but not to the same extent as the reduction in the basic amino acids. 4. Animal feeding-stuffs, whether unheated, industrially processed or diliberately heated, appeared to react with Acid Orange 12 in the same way as the model systems (selected to represent three types of heat damage: 'advanced' and 'early' Maillard and protein-protein damage). 5. Remazol blue binding values and fluorodinitrobenzene (RDNB)-reactive lysine values were similarly reduced in materials that had been severely heated, either with or without added sugars; however, when protein and glucose had reacted under mild conditions the fall in Remazol blue binding was less than that in FDNB-reactive lysine. 6. For the model materials, binding with cresol red was, in general, higher for heated samples but the results showed no correlation with FDNB-reactive lysine values. For meat and groundnut meals, changes in values after heat treatment were smaller than those that have been reported for soya-bean meals."} {"id": "PMID:163641", "title": "Activation of 3',5'-cyclic adenosine monophosphate phosphodiesterase by calcium ion and a protein activator.", "content": "3',5'-CAMP phosphodiesterase was partially purified from bovine cerebral cortex. A heat-stable activating factor was separated from the enzyme by chromatography on DEAE-cellulose. The enzyme in crude ammonium sulfate fractions was stimulated by 5 mM CaCl2. This stimulation was reversed by the calcium chelator EGTA. The main phosphodiesterase peak obtained by DEAE-cellulose chromatography was not stimulated by Ca2+. Upon addition of column effluent containing a heat stable factor, Ca2+ activation was restored. Protein activator was inactive when endogenous contaminating Ca2+ was complexed with EGTA. It was concluded that activation of phosphodiesterase requires the presence of both activator and Ca1+. From an analysis of activation of cGMP hydrolysis a kinetic model for the interaction of Ca2+ and protein activator with the phosphodiesterase was developed. Heterotropic cooperativity between the binding of Ca2+ and protein activator to the phosphodiesterase was observed, i.e., Ca1+ decreased the apparent dissociation constant for protein activator and protein activator decreased the apparent dissociation constant for Ca2+.", "contents": "Activation of 3',5'-cyclic adenosine monophosphate phosphodiesterase by calcium ion and a protein activator. 3',5'-CAMP phosphodiesterase was partially purified from bovine cerebral cortex. A heat-stable activating factor was separated from the enzyme by chromatography on DEAE-cellulose. The enzyme in crude ammonium sulfate fractions was stimulated by 5 mM CaCl2. This stimulation was reversed by the calcium chelator EGTA. The main phosphodiesterase peak obtained by DEAE-cellulose chromatography was not stimulated by Ca2+. Upon addition of column effluent containing a heat stable factor, Ca2+ activation was restored. Protein activator was inactive when endogenous contaminating Ca2+ was complexed with EGTA. It was concluded that activation of phosphodiesterase requires the presence of both activator and Ca1+. From an analysis of activation of cGMP hydrolysis a kinetic model for the interaction of Ca2+ and protein activator with the phosphodiesterase was developed. Heterotropic cooperativity between the binding of Ca2+ and protein activator to the phosphodiesterase was observed, i.e., Ca1+ decreased the apparent dissociation constant for protein activator and protein activator decreased the apparent dissociation constant for Ca2+."} {"id": "PMID:163638", "title": "Pseudogout in ochronosis. Report of a case.", "content": "Calcium pyrophosphate dihydrate crystals were identified in synovial fluid white blood cells during an episode of acute arthritis in a patient with ochronosis and chondrocalcinosis. Review of the histories and radiographs of 5 other patients with ochronosis demonstrated two additional instances of chondrocalcinosis. Both of these patients had episodes of arthritis consistent with pseudogout. This suggests that pseudogout, which has been found in increased incidence in some metabolic diseases, may also be more common in ochronosis.", "contents": "Pseudogout in ochronosis. Report of a case. Calcium pyrophosphate dihydrate crystals were identified in synovial fluid white blood cells during an episode of acute arthritis in a patient with ochronosis and chondrocalcinosis. Review of the histories and radiographs of 5 other patients with ochronosis demonstrated two additional instances of chondrocalcinosis. Both of these patients had episodes of arthritis consistent with pseudogout. This suggests that pseudogout, which has been found in increased incidence in some metabolic diseases, may also be more common in ochronosis."} {"id": "PMID:163639", "title": "Immunoglobulin deposits in skin in systemic lupus erythematosus.", "content": "Immunoglobulin deposits in the dermal-epidermal junction of clinically normal skin from patients with SLE were eluted by acid buffer. The eluates contained antinuclear and antibasement membrane antibody activities. The anti-BM antibody reacted with skin and esophageal but not glomerular basement membrane. Enzymatic studies indicated that the antibody reacted with carbohydrate moeities in the basement membrane. The anti-BM antibody was not present in corresponding sera of SLE patients.", "contents": "Immunoglobulin deposits in skin in systemic lupus erythematosus. Immunoglobulin deposits in the dermal-epidermal junction of clinically normal skin from patients with SLE were eluted by acid buffer. The eluates contained antinuclear and antibasement membrane antibody activities. The anti-BM antibody reacted with skin and esophageal but not glomerular basement membrane. Enzymatic studies indicated that the antibody reacted with carbohydrate moeities in the basement membrane. The anti-BM antibody was not present in corresponding sera of SLE patients."} {"id": "PMID:163642", "title": "General aspects of hydrophobic chromatography. Adsorption and elution characteristics of some skeletal muscle enzymes.", "content": "If the degree of substitution of Sepharose 4 B with alpha-alkylamines is varied gels of different hydrophobicity are produced. Proteins can be adsorbed when a critical hydrophobicity (ca. 10-12 alkyl residues/Sepharose sphere) is reached. The enzymes phosphorylase kinase, phosphorylase phosphatase, 3',5'-cAMP dependent protein kinase, glycogen synthetase, and phosphorylase b are successively adsorbed as the hydrophobicity of the Sepharose is increased. The capacity of the gels for these enzymes and protein in general increases exponentially reaches plateau values as a function of the degree of substitution. There is no indication of a restriction of the hydrophobic centers for a given protein. The critical hydrophobicity needed to adsorb proteins can either be otained in the above manner or by elongation of the employed alkylamine at a constant degree of substitution. Additonally, as the hydrophobicity of a gel is increased higher binding forces result and desorption of proteins requires an augmentation of the salt concentration in the elution buffer. Elution of proteins from a hydrophobic matrix can be described in terms of salting-in phenomena since desorption is dependent on the type of salt employed and not on the ionic strength alone. This also rules out ionic interactions as a major factor in adsorption per se. By rationally controlling the hydrophobicity of a Sepharose gel the adsorption and elution of a protein may be thus establised that its purification or elimination can be optimally performed.", "contents": "General aspects of hydrophobic chromatography. Adsorption and elution characteristics of some skeletal muscle enzymes. If the degree of substitution of Sepharose 4 B with alpha-alkylamines is varied gels of different hydrophobicity are produced. Proteins can be adsorbed when a critical hydrophobicity (ca. 10-12 alkyl residues/Sepharose sphere) is reached. The enzymes phosphorylase kinase, phosphorylase phosphatase, 3',5'-cAMP dependent protein kinase, glycogen synthetase, and phosphorylase b are successively adsorbed as the hydrophobicity of the Sepharose is increased. The capacity of the gels for these enzymes and protein in general increases exponentially reaches plateau values as a function of the degree of substitution. There is no indication of a restriction of the hydrophobic centers for a given protein. The critical hydrophobicity needed to adsorb proteins can either be otained in the above manner or by elongation of the employed alkylamine at a constant degree of substitution. Additonally, as the hydrophobicity of a gel is increased higher binding forces result and desorption of proteins requires an augmentation of the salt concentration in the elution buffer. Elution of proteins from a hydrophobic matrix can be described in terms of salting-in phenomena since desorption is dependent on the type of salt employed and not on the ionic strength alone. This also rules out ionic interactions as a major factor in adsorption per se. By rationally controlling the hydrophobicity of a Sepharose gel the adsorption and elution of a protein may be thus establised that its purification or elimination can be optimally performed."} {"id": "PMID:163643", "title": "Simple alkanethiol groups for temporary blocking of sulfhydryl groups of enzymes.", "content": "New reagents for the temporary blocking of active or accessible sulfhydryl groups of enzymes have been developed. These reagents, which are either alkyl alkanethiolsulfonates or alkoxycarbonylalkyl disulfides, rapidly and quantitatively place various RS- groups on the sulfhydryls to generate mixed disulfides. In all cases native enzymes can be regenerated with either dithiothreitol or beta-mercaptoethanol. In general the temporary blocking groups also afford total protection against normally inhibitory thiol blocking agents. When RS- groups were attached to rabbit muscle creatine kinase (EC 2.7.3.2), a trend toward lower residual activities with increasing bulk was observed. Treatment of the native creatine kinase with 14CH3HgC1 led to incorporation of greater than 1 equiv of CH3Hg- group per subunit. This CH3Hg- blocked enzyme was fully active, and the blocking group afforded no protection against iodoacetamide. These results suggest that CH3Hg- and the RS- groups are modifying two different sulhydryl groups on the enzyme. When papain (EC 3.4.4.10) was treated with excess methyl methanethiolsulfonate. complete and rapid inhibition was observed, and 1 equiv of CH3S- was incorporated/mol of active enzyme. Complete protection against normally inhibitory 5,5'-dithiobis(2-nitrobenzoic acid) was afforded by the temporary blocking group. When rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) was titrated with methyl methanethiolsulfonate, two sulfhydryl groups per subunit were found to be modified, one much more rapidly than the other. If one extrapolates the initial slope of the titration curve, the inactivation of the enzyme would be complete after modification of a single cysteinyl residue per subunit.", "contents": "Simple alkanethiol groups for temporary blocking of sulfhydryl groups of enzymes. New reagents for the temporary blocking of active or accessible sulfhydryl groups of enzymes have been developed. These reagents, which are either alkyl alkanethiolsulfonates or alkoxycarbonylalkyl disulfides, rapidly and quantitatively place various RS- groups on the sulfhydryls to generate mixed disulfides. In all cases native enzymes can be regenerated with either dithiothreitol or beta-mercaptoethanol. In general the temporary blocking groups also afford total protection against normally inhibitory thiol blocking agents. When RS- groups were attached to rabbit muscle creatine kinase (EC 2.7.3.2), a trend toward lower residual activities with increasing bulk was observed. Treatment of the native creatine kinase with 14CH3HgC1 led to incorporation of greater than 1 equiv of CH3Hg- group per subunit. This CH3Hg- blocked enzyme was fully active, and the blocking group afforded no protection against iodoacetamide. These results suggest that CH3Hg- and the RS- groups are modifying two different sulhydryl groups on the enzyme. When papain (EC 3.4.4.10) was treated with excess methyl methanethiolsulfonate. complete and rapid inhibition was observed, and 1 equiv of CH3S- was incorporated/mol of active enzyme. Complete protection against normally inhibitory 5,5'-dithiobis(2-nitrobenzoic acid) was afforded by the temporary blocking group. When rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) was titrated with methyl methanethiolsulfonate, two sulfhydryl groups per subunit were found to be modified, one much more rapidly than the other. If one extrapolates the initial slope of the titration curve, the inactivation of the enzyme would be complete after modification of a single cysteinyl residue per subunit."} {"id": "PMID:163644", "title": "The specificity of different classes of ethylating agents toward various sites in RNA.", "content": "The alkyl products of neutral in vitro ethylation of TMV-RNA by [14C]diethyl sulfate, [14C]ethyl methanesulfonate, and [14C]ethylnitrosourea have been determined and found to differ significantly depending on the ethylating agent. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of TMV-RNA in the following order: 7-ethylguanine greater than 1-ethyladenine, 3-ethylcytidine greater than 7-ethyladenine, 3-ethyladenine, O6-ethylguanosine, 3-ethylguanine. Ethyl methanesulfonate was more specific for the 7 position of guanine, and other derivatives were found in lesser amounts than with diethyl sulfate. Neither reagent caused the formation of detectable amounts (smaller than 0.26 percent) of 1-ethylguanine, 1,7-diethylguanine, N2-ethylguanine, N6-ethyladenine, N4-ethylcytidine, or 3-ethyluridine. Identified ethyl bases account for over 85% of the total radioactivity of [14C]ethyl methanesulfonate and [14C]diethyl sulfate treated TMV-RNA. Phosphate alkylation accounts for about 13 and 1%, respectively, In contrast, [14C]ethylnitrosourea-treated TMV-RNA, while reacting to a similar extent (15-70 ethyl groups/6400 nucleotides), is found to cause considerably more phosphate alkylation. Upon either U4A RNase or acid hydrolysis up to 60% of the radioactivity is found as volatile ethyl groupw in the form of [14C]ethanol, and a further 15% appears to be primarily ethyl phosphate and nucleosides with ethylated phosphate. Of the remaining radioactivity, half is found as O6-ethylguanosine, the major identified ethyl nucleoside. Other ethyl bases found in ethylnitrosourea-treated TMV-RNA are 7-ethylguanine greater than 1-ethyladenine, 3-ethyladenine, 7-ethyladenine, 3-ethylcytidine, and 3-ethylguanine. It appears that ethylnitrosourea preferentially alkylates oxygens, and that formation of phosphotriesters is by far the predominant chemical event. Since the number of ethyl groups introduced into TMV-RNA by ethylnitrosourea is similar to the number of lethal events, one may conclude that phosphate alkylation leads to loss of infectivity. None of the three ethylating agents studied are strongly mutagenic on TMV-RNA or TMV. The role of phosphate alkylation in regard to in vivo mutagenesis and oncogenesis remains to be established. At present it appears possible that the extent of this reaction may correlate better with the oncogenic effectiveness of different ethylating agents, than the extent of any base reaction. Unfractionated HeLa cell RNA is ethylated primarily in acid labile manner even by diethyl sulfate and ethyl methanesulfonate, a fact that is attributed to its high content of low molecular weight trna rich in terminal phosphates which alkylate readily.", "contents": "The specificity of different classes of ethylating agents toward various sites in RNA. The alkyl products of neutral in vitro ethylation of TMV-RNA by [14C]diethyl sulfate, [14C]ethyl methanesulfonate, and [14C]ethylnitrosourea have been determined and found to differ significantly depending on the ethylating agent. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of TMV-RNA in the following order: 7-ethylguanine greater than 1-ethyladenine, 3-ethylcytidine greater than 7-ethyladenine, 3-ethyladenine, O6-ethylguanosine, 3-ethylguanine. Ethyl methanesulfonate was more specific for the 7 position of guanine, and other derivatives were found in lesser amounts than with diethyl sulfate. Neither reagent caused the formation of detectable amounts (smaller than 0.26 percent) of 1-ethylguanine, 1,7-diethylguanine, N2-ethylguanine, N6-ethyladenine, N4-ethylcytidine, or 3-ethyluridine. Identified ethyl bases account for over 85% of the total radioactivity of [14C]ethyl methanesulfonate and [14C]diethyl sulfate treated TMV-RNA. Phosphate alkylation accounts for about 13 and 1%, respectively, In contrast, [14C]ethylnitrosourea-treated TMV-RNA, while reacting to a similar extent (15-70 ethyl groups/6400 nucleotides), is found to cause considerably more phosphate alkylation. Upon either U4A RNase or acid hydrolysis up to 60% of the radioactivity is found as volatile ethyl groupw in the form of [14C]ethanol, and a further 15% appears to be primarily ethyl phosphate and nucleosides with ethylated phosphate. Of the remaining radioactivity, half is found as O6-ethylguanosine, the major identified ethyl nucleoside. Other ethyl bases found in ethylnitrosourea-treated TMV-RNA are 7-ethylguanine greater than 1-ethyladenine, 3-ethyladenine, 7-ethyladenine, 3-ethylcytidine, and 3-ethylguanine. It appears that ethylnitrosourea preferentially alkylates oxygens, and that formation of phosphotriesters is by far the predominant chemical event. Since the number of ethyl groups introduced into TMV-RNA by ethylnitrosourea is similar to the number of lethal events, one may conclude that phosphate alkylation leads to loss of infectivity. None of the three ethylating agents studied are strongly mutagenic on TMV-RNA or TMV. The role of phosphate alkylation in regard to in vivo mutagenesis and oncogenesis remains to be established. At present it appears possible that the extent of this reaction may correlate better with the oncogenic effectiveness of different ethylating agents, than the extent of any base reaction. Unfractionated HeLa cell RNA is ethylated primarily in acid labile manner even by diethyl sulfate and ethyl methanesulfonate, a fact that is attributed to its high content of low molecular weight trna rich in terminal phosphates which alkylate readily."} {"id": "PMID:163645", "title": "Structural studies on carcinoembryonic antigen. Periodate oxidation.", "content": "Periodate oxidation has been applied to examine the carbohydrate structure of carcinoembryonic antigen (CEA) and the possible role of the carbohydrate residues in its antigenic activity. Sialic acid (N-acetylneuraminic acid) and fucose were completely destroyed, and galactose and mannose were partially destroyed by a single periodate treatment. Serial periodate treatment (Smith degradation) destroyed additional amounts of galactose and mannose as well as significant amounts of N-acetylglucosamine. Prior removal of sialic acid by neuraminidase treatment led to increased destruction of galactose by periodate. Antigenic activity persisted indicating that the residues destroyed played little, if any, part in the antigenicity of CEA. These results yield an initial view of the structural arrangement of the carbohydrate residues in the CEA molecule.", "contents": "Structural studies on carcinoembryonic antigen. Periodate oxidation. Periodate oxidation has been applied to examine the carbohydrate structure of carcinoembryonic antigen (CEA) and the possible role of the carbohydrate residues in its antigenic activity. Sialic acid (N-acetylneuraminic acid) and fucose were completely destroyed, and galactose and mannose were partially destroyed by a single periodate treatment. Serial periodate treatment (Smith degradation) destroyed additional amounts of galactose and mannose as well as significant amounts of N-acetylglucosamine. Prior removal of sialic acid by neuraminidase treatment led to increased destruction of galactose by periodate. Antigenic activity persisted indicating that the residues destroyed played little, if any, part in the antigenicity of CEA. These results yield an initial view of the structural arrangement of the carbohydrate residues in the CEA molecule."} {"id": "PMID:163646", "title": "Phase separations in phospholipd membranes.", "content": "Phase diagrams representing lateral phase separations in the plane of lipid bilayer membranes have been determined for binary mixtures containing dielaidoylphosphatidylcholine together with dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, and dipalmitoylphosphatidylethanolamine. The phase diagrams were deduced from observations of the temperature dependence of the paramagnetic resonance spectra of low concentrations of spin-labels incorporated in these bilayer membranes. In one case, the binary mixture of dipalmitoylphosphatidylethamine and dielaidoylphosphatidylcholine, evidence has been obtained for fluid-fluid immiscibility, in specified temperature and compoistion ranges. This immiscibility could give a lateral phase separation into fluid domains in the plane of the membrane, and/or a transverse phase separation into an asymmetrical bilayer membrane, and/or possibly disco ntinuous bilayer membranes of different composition. An asymmetrical bilayer membrane can be expected on theoretical grounds to form a nonplanar membrane.", "contents": "Phase separations in phospholipd membranes. Phase diagrams representing lateral phase separations in the plane of lipid bilayer membranes have been determined for binary mixtures containing dielaidoylphosphatidylcholine together with dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, and dipalmitoylphosphatidylethanolamine. The phase diagrams were deduced from observations of the temperature dependence of the paramagnetic resonance spectra of low concentrations of spin-labels incorporated in these bilayer membranes. In one case, the binary mixture of dipalmitoylphosphatidylethamine and dielaidoylphosphatidylcholine, evidence has been obtained for fluid-fluid immiscibility, in specified temperature and compoistion ranges. This immiscibility could give a lateral phase separation into fluid domains in the plane of the membrane, and/or a transverse phase separation into an asymmetrical bilayer membrane, and/or possibly disco ntinuous bilayer membranes of different composition. An asymmetrical bilayer membrane can be expected on theoretical grounds to form a nonplanar membrane."} {"id": "PMID:163647", "title": "Beef-heart submitochondrial particles: a mixture of mitochondrial inner and outer membranes.", "content": "1. EPR spectra at 9 GHz and 83 degrees K of NADH-reduced anaerobic beef-heart submitochondrial particles, prepared from mitochondria by sonication and centrifugation, contain a signal (gz equals to 2.01, gy equals to 1.94, gx equals to 1.89) due to an iron-sulphur center of the mitochondrial outer membrane. 2. The ratio of inner and outer membranes in submitochondrial particles is not greatly different from that in beef-heart mitochondria. 3. Beef-heart submitochondrial particles free from outer-membrane contamination have been prepared by free-flow electrophoresis. EPR spectra at 83 degrees K of such particles are presented.", "contents": "Beef-heart submitochondrial particles: a mixture of mitochondrial inner and outer membranes. 1. EPR spectra at 9 GHz and 83 degrees K of NADH-reduced anaerobic beef-heart submitochondrial particles, prepared from mitochondria by sonication and centrifugation, contain a signal (gz equals to 2.01, gy equals to 1.94, gx equals to 1.89) due to an iron-sulphur center of the mitochondrial outer membrane. 2. The ratio of inner and outer membranes in submitochondrial particles is not greatly different from that in beef-heart mitochondria. 3. Beef-heart submitochondrial particles free from outer-membrane contamination have been prepared by free-flow electrophoresis. EPR spectra at 83 degrees K of such particles are presented."} {"id": "PMID:163648", "title": "Flash photolysis electron spin resonance studies of the electron acceptor species at low temperatures in photosystem I of spinach subchloroplast particles.", "content": "The light-induced electron spin resonance signals of Photosystem I spinach subchloroplast particles have been studied at approximately 6 degrees K. Using the technique of flash photolysis-electron spin resonance with actinic illumination at 647 nm, a kinetic analysis of the previously observed bound ferredoxin ESR signals was carried out. Signal I (P700+) exhibits a partial light-reversible behavior at 6 degrees K so it was expected that if the bound ferredoxin is the primary acceptor of Photosystem I, it should also exhibit a partial reversible behavior. However, none of the bound ferredoxin ESR signals showed any such light reversible behavior. A search to wider fields revealed two components which did exhibit the expected kinetic behavior. These components are very broad (about 80 G) and are centered at g equals to 1.75 and g equals to 2.07. These two components exhibit the expected characteristics of the primary electron acceptor. A model is presented to account for the reversible and irreversible photochemical changes in Photosystem I. The possible identity of the primary acceptor responsible for these two new components, is discussed in terms of the available information. The primary acceptor may be an iron-sulfur protein, but not of the type characteristic of the bound or water-soluble ferredoxins found so far in chloroplasts.", "contents": "Flash photolysis electron spin resonance studies of the electron acceptor species at low temperatures in photosystem I of spinach subchloroplast particles. The light-induced electron spin resonance signals of Photosystem I spinach subchloroplast particles have been studied at approximately 6 degrees K. Using the technique of flash photolysis-electron spin resonance with actinic illumination at 647 nm, a kinetic analysis of the previously observed bound ferredoxin ESR signals was carried out. Signal I (P700+) exhibits a partial light-reversible behavior at 6 degrees K so it was expected that if the bound ferredoxin is the primary acceptor of Photosystem I, it should also exhibit a partial reversible behavior. However, none of the bound ferredoxin ESR signals showed any such light reversible behavior. A search to wider fields revealed two components which did exhibit the expected kinetic behavior. These components are very broad (about 80 G) and are centered at g equals to 1.75 and g equals to 2.07. These two components exhibit the expected characteristics of the primary electron acceptor. A model is presented to account for the reversible and irreversible photochemical changes in Photosystem I. The possible identity of the primary acceptor responsible for these two new components, is discussed in terms of the available information. The primary acceptor may be an iron-sulfur protein, but not of the type characteristic of the bound or water-soluble ferredoxins found so far in chloroplasts."} {"id": "PMID:163649", "title": "A rapid, light-induced transient in electron paramagnetic resonance signal II activated upon inhibition of photosynthetic oxygen evolution.", "content": "A rapid, light-induced reversible component in Signal II is observed upon inhibition of oxygen evolution in broken spinach chloroplasts. The inhibitory treatments used include Tris washing, heat, treatment with chaotropic agents, and aging. This new Signal II component is in a 1 : 1 ratio with Signal I (P700). Its formation corresponds to a light-induced oxidation which occurs in less than 500 mus. The subsequent decay of the radical results from a reduction which occurs more rapidly as this free radical component is complete following a single 10-mus flash, and it occurs with a quantum efficiency similar to that observed for Signal I formation. Red light is more effective than far-red light in the generation of this species, and, in preilluminated chloroplasts, 3-(3,4-dichlorophenyl)-1,1-dimethylurea blocks its formation. Inhibition studies show that the decline in oxygen evolution parallels the activation of this Signal II component. These results are interpreted in terms of a model in which two pathways, one involving water, the other involving the rapid Signal II component, compete for oxidizing equivalents generated by Photosystem II. In broken chloroplasts this Signal II pathway is deactivated and water is the principal electron donor. However, upon inhibition of oxygen evolution, the Signal II pathway is activated.", "contents": "A rapid, light-induced transient in electron paramagnetic resonance signal II activated upon inhibition of photosynthetic oxygen evolution. A rapid, light-induced reversible component in Signal II is observed upon inhibition of oxygen evolution in broken spinach chloroplasts. The inhibitory treatments used include Tris washing, heat, treatment with chaotropic agents, and aging. This new Signal II component is in a 1 : 1 ratio with Signal I (P700). Its formation corresponds to a light-induced oxidation which occurs in less than 500 mus. The subsequent decay of the radical results from a reduction which occurs more rapidly as this free radical component is complete following a single 10-mus flash, and it occurs with a quantum efficiency similar to that observed for Signal I formation. Red light is more effective than far-red light in the generation of this species, and, in preilluminated chloroplasts, 3-(3,4-dichlorophenyl)-1,1-dimethylurea blocks its formation. Inhibition studies show that the decline in oxygen evolution parallels the activation of this Signal II component. These results are interpreted in terms of a model in which two pathways, one involving water, the other involving the rapid Signal II component, compete for oxidizing equivalents generated by Photosystem II. In broken chloroplasts this Signal II pathway is deactivated and water is the principal electron donor. However, upon inhibition of oxygen evolution, the Signal II pathway is activated."} {"id": "PMID:163650", "title": "The rapid component of electron paramagnetic resonance signal II: a candidate for the physiological donor to photosystem II in spinach chloroplasts.", "content": "Rapid light-induced transients in EPR Signal IIf (F-+) are observed in 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-treated, Tris-washed chloroplasts until the state F P680 Q minus is reached. In the absence of exogenous redox mediators several flashes are required to saturate this photoinactive state. However, the Signal IIf transient is observed on only the first flash following DCMU addition if an efficient donor to Signal IIf, phenylenediamine or hydroquinone, is present. Complementary polarographic measurements show that under these conditions oxidized phenylenediamine is produced only on the first flash of a series. The DCMU inhibition of Signal IIf can be completely relieved by oxidative titration of a one-electron reductant with E'Os.o equals to + 480 mV. At high reduction potentials the decay time of Signal IIf is constant at about 300 ms, whereas in the absence of DCMU the decay time is longer and increases with increasing reduction potential. A model is proposed in which Q minus, the reduced Photosystem II primary acceptor, and D, a one-electron 480 mV donor endogenous to the chloroplast suspension, compete in the reduction of Signal IIf (F-+). At high potentials D is oxidized in the dark, and the (Q-+F-+) back reaction regenerates the photoactive F P680 Q state. The electrochemical and kinetic evidence is consistent with the hypothesis that the Signal IIf species, F, is identical with Z, the physiological donor to P680.", "contents": "The rapid component of electron paramagnetic resonance signal II: a candidate for the physiological donor to photosystem II in spinach chloroplasts. Rapid light-induced transients in EPR Signal IIf (F-+) are observed in 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-treated, Tris-washed chloroplasts until the state F P680 Q minus is reached. In the absence of exogenous redox mediators several flashes are required to saturate this photoinactive state. However, the Signal IIf transient is observed on only the first flash following DCMU addition if an efficient donor to Signal IIf, phenylenediamine or hydroquinone, is present. Complementary polarographic measurements show that under these conditions oxidized phenylenediamine is produced only on the first flash of a series. The DCMU inhibition of Signal IIf can be completely relieved by oxidative titration of a one-electron reductant with E'Os.o equals to + 480 mV. At high reduction potentials the decay time of Signal IIf is constant at about 300 ms, whereas in the absence of DCMU the decay time is longer and increases with increasing reduction potential. A model is proposed in which Q minus, the reduced Photosystem II primary acceptor, and D, a one-electron 480 mV donor endogenous to the chloroplast suspension, compete in the reduction of Signal IIf (F-+). At high potentials D is oxidized in the dark, and the (Q-+F-+) back reaction regenerates the photoactive F P680 Q state. The electrochemical and kinetic evidence is consistent with the hypothesis that the Signal IIf species, F, is identical with Z, the physiological donor to P680."} {"id": "PMID:163652", "title": "DNA-binding proteins from Novikoff hepatoma cells.", "content": "In 0.05 M NaCl, 6-8% of the total soluble proteins from Novikoff hepatoma cells bind rapidly and reversibly to columns containing either heterologous or homologous DNA adsorbed to cellulose. These proteins can be eluted by buffer containing 2.0 M NaCl. 0.5-1% of the total protein exhibits a 7-17-fold preference for rat DNA over Escherichia coli DNA. 1-1.5% of the proteins bind DNA so strongly that elution cannot be effected by 4.0 M NaCl but can be accomplished by deoxyribonuclease I treatment of the columns. DNA-binding proteins eluted by 2.0 M NaCl were labeled with 125I or 131I and characterized by sodium dodecylsulfate-polyacrylamide gel electrophoresis and isoelectric focusing. These experiments indicate that DNA-binding proteins represent a discrete subset of the total soluble protein. Many similarities were noted between the major components of the homologous and heterologous DNA-binding fractions.", "contents": "DNA-binding proteins from Novikoff hepatoma cells. In 0.05 M NaCl, 6-8% of the total soluble proteins from Novikoff hepatoma cells bind rapidly and reversibly to columns containing either heterologous or homologous DNA adsorbed to cellulose. These proteins can be eluted by buffer containing 2.0 M NaCl. 0.5-1% of the total protein exhibits a 7-17-fold preference for rat DNA over Escherichia coli DNA. 1-1.5% of the proteins bind DNA so strongly that elution cannot be effected by 4.0 M NaCl but can be accomplished by deoxyribonuclease I treatment of the columns. DNA-binding proteins eluted by 2.0 M NaCl were labeled with 125I or 131I and characterized by sodium dodecylsulfate-polyacrylamide gel electrophoresis and isoelectric focusing. These experiments indicate that DNA-binding proteins represent a discrete subset of the total soluble protein. Many similarities were noted between the major components of the homologous and heterologous DNA-binding fractions."} {"id": "PMID:163653", "title": "Adsorption of small molecules to bovine serum albumin studied by the spin-probe method.", "content": "A spin-probe technique is used for quantitative EPR studies of adsorption of small molecules on globular proteins, of the rigidity of their binding to the protein and of the polarity of the environment. In the case of bovine serum albumin it is shown that nitroxyl radical (2, 2, 6, 6-tetramethyl-4-oxy-1-oxyl-piperidine)-stearate (I) has an adsorption behaviour similar to that of the fatty acids, nitroxyl radical (2, 2,4, 4-tetramethyl-1, 2, 3, 4-tetrahydro-5, 6-benzo-gamma-carboline-3-oxyl) (II) to that of the tryptophan molecule. Radical I rotates relative to the protein molecule, while Radical II is rigidly bound to the protein.", "contents": "Adsorption of small molecules to bovine serum albumin studied by the spin-probe method. A spin-probe technique is used for quantitative EPR studies of adsorption of small molecules on globular proteins, of the rigidity of their binding to the protein and of the polarity of the environment. In the case of bovine serum albumin it is shown that nitroxyl radical (2, 2, 6, 6-tetramethyl-4-oxy-1-oxyl-piperidine)-stearate (I) has an adsorption behaviour similar to that of the fatty acids, nitroxyl radical (2, 2,4, 4-tetramethyl-1, 2, 3, 4-tetrahydro-5, 6-benzo-gamma-carboline-3-oxyl) (II) to that of the tryptophan molecule. Radical I rotates relative to the protein molecule, while Radical II is rigidly bound to the protein."} {"id": "PMID:163654", "title": "Insoluble non-collagenous cartilage glycoproteins with aggregating sub-units.", "content": "Two insoluble non-collagenous glycoprotein fractions (A and G) have been separated from puppy rib cartilage, following extraction of most of the proteoglycan and digestion of the insoluble residue with purified collagenase. After reduction, alkylation and extraction with sodium dodecylsulfate most of each protein is solubilized. Gel electrophoresis of solubilized A or G shows the presence of either one or two bands and gel chromatography shows both high and low molecular weight peaks. The production of a low molecular weight electrophoresis band from the high molecular weight Sephadex fraction indicates that there is aggregation and disaggregation of sub-units in sodium dodecylsulfate. Both A and G are high in aspartate plus glutamate and have a low hydroxyproline content. The insoluble A and G both contain hexose, uronic acid, galactosamine, glucosamine and a small amount of sialic acid, but they differ in their contents of hexose and six amino acids. They both form single bands in CsCl gradients but they differ in density. Electron microscopy shows that both insoluble glycoprotein fractions stain with lead, ruthenium red, or alcian blue plus phosphotungstate and that G contains many fine filaments. Material with the same appearance and staining properties was found to occur on the surface of collagen fibres in the undigested cartilage residue.", "contents": "Insoluble non-collagenous cartilage glycoproteins with aggregating sub-units. Two insoluble non-collagenous glycoprotein fractions (A and G) have been separated from puppy rib cartilage, following extraction of most of the proteoglycan and digestion of the insoluble residue with purified collagenase. After reduction, alkylation and extraction with sodium dodecylsulfate most of each protein is solubilized. Gel electrophoresis of solubilized A or G shows the presence of either one or two bands and gel chromatography shows both high and low molecular weight peaks. The production of a low molecular weight electrophoresis band from the high molecular weight Sephadex fraction indicates that there is aggregation and disaggregation of sub-units in sodium dodecylsulfate. Both A and G are high in aspartate plus glutamate and have a low hydroxyproline content. The insoluble A and G both contain hexose, uronic acid, galactosamine, glucosamine and a small amount of sialic acid, but they differ in their contents of hexose and six amino acids. They both form single bands in CsCl gradients but they differ in density. Electron microscopy shows that both insoluble glycoprotein fractions stain with lead, ruthenium red, or alcian blue plus phosphotungstate and that G contains many fine filaments. Material with the same appearance and staining properties was found to occur on the surface of collagen fibres in the undigested cartilage residue."} {"id": "PMID:163655", "title": "A simple and inexpensive method for the preparation of (beta,gamma-32P) guanosine 5'-triphosphate.", "content": "A rapid and inexpensive method has been developed for the synthesis of 32P-labeled guanosine 5'-triphosphate (GTP). When yolk platelets isolated from brine shrimp cysts are incubated with 32PPi at pH 5.8 and in the presence of 10 mM MgCl2 and 5 mM dithiothreitol, the primary compound formed is [beta,gamma-32P]GTP. The synthetic reaction is catalyzed by the yolk platelet enzyme, GTP : GTP guanylyltransferase, which has been demonstrated to be important in the biosynthesis of diguanosine 5'-tetraphosphate (Gp4G), the major purine nucleotide in brine shrimp yolk platelets and encysted embryos.", "contents": "A simple and inexpensive method for the preparation of (beta,gamma-32P) guanosine 5'-triphosphate. A rapid and inexpensive method has been developed for the synthesis of 32P-labeled guanosine 5'-triphosphate (GTP). When yolk platelets isolated from brine shrimp cysts are incubated with 32PPi at pH 5.8 and in the presence of 10 mM MgCl2 and 5 mM dithiothreitol, the primary compound formed is [beta,gamma-32P]GTP. The synthetic reaction is catalyzed by the yolk platelet enzyme, GTP : GTP guanylyltransferase, which has been demonstrated to be important in the biosynthesis of diguanosine 5'-tetraphosphate (Gp4G), the major purine nucleotide in brine shrimp yolk platelets and encysted embryos."} {"id": "PMID:163656", "title": "Three DNA polymerases of rat ascites hepatoma cells: properties of the enzymes and effect of RNA synthesis on the reactions.", "content": "Three different DNA polymerases have been isolated from rat ascites hepatoma cells [1--3]. The molecular weight of a DNA polymerase (polymerase C) purified from the soluble fraction of the cells was estimated to be 142 000 by sedimentation on a sucrose gradient, while the molecular weights of two DNA polymerases (polymerase P-1 and P-2) purified from nuclear membrane-chromatin fraction were estimated to be 117 000 and 44 000, respectively, by the same method. Under certain conditions, the poly (dT) strand of poly[(dA)-(dT)] was copied well by the polymerases, especially by the nuclear polymerases. Poly (dC) was a good template for the high molecular weight DNA polymerases C and P-1, but poly(dT) and poly(dA) were not effective templates. By addition of complementary oligoribonucleotides, the single-stranded deoxypolymers were copied by the high molecular weight polymerases C and P-1. When single-stranded fd phage DNA was used as template, the polymerization reactions by the high molecular weight polymerases were stimulated by the concomitant synthesis of RNA. This indicates that the oligoribonucleotide acts as a primer in these reactions.", "contents": "Three DNA polymerases of rat ascites hepatoma cells: properties of the enzymes and effect of RNA synthesis on the reactions. Three different DNA polymerases have been isolated from rat ascites hepatoma cells [1--3]. The molecular weight of a DNA polymerase (polymerase C) purified from the soluble fraction of the cells was estimated to be 142 000 by sedimentation on a sucrose gradient, while the molecular weights of two DNA polymerases (polymerase P-1 and P-2) purified from nuclear membrane-chromatin fraction were estimated to be 117 000 and 44 000, respectively, by the same method. Under certain conditions, the poly (dT) strand of poly[(dA)-(dT)] was copied well by the polymerases, especially by the nuclear polymerases. Poly (dC) was a good template for the high molecular weight DNA polymerases C and P-1, but poly(dT) and poly(dA) were not effective templates. By addition of complementary oligoribonucleotides, the single-stranded deoxypolymers were copied by the high molecular weight polymerases C and P-1. When single-stranded fd phage DNA was used as template, the polymerization reactions by the high molecular weight polymerases were stimulated by the concomitant synthesis of RNA. This indicates that the oligoribonucleotide acts as a primer in these reactions."} {"id": "PMID:163657", "title": "Participation of manganese ions complexed with tRNA in the interaction with amino acids and dipeptides.", "content": "Carboxyl groups of glycine, beta-alanine, gamma-aminobutyric acid and diglycine interact with Mn2+ coordinated by tRNA, as revealed by 1H and 13C NMR studies. The amino groups of these compounds interact with tRNA phosphate groups. The distances between the coordinated Mn2+ and carboxyl groups and the alpha-protons of glycine were determined. The role of Mn2+ and Mg2+ complexed with nucleic acids in the formation of specific complexes between proteins and nucleic acids is discussed.", "contents": "Participation of manganese ions complexed with tRNA in the interaction with amino acids and dipeptides. Carboxyl groups of glycine, beta-alanine, gamma-aminobutyric acid and diglycine interact with Mn2+ coordinated by tRNA, as revealed by 1H and 13C NMR studies. The amino groups of these compounds interact with tRNA phosphate groups. The distances between the coordinated Mn2+ and carboxyl groups and the alpha-protons of glycine were determined. The role of Mn2+ and Mg2+ complexed with nucleic acids in the formation of specific complexes between proteins and nucleic acids is discussed."} {"id": "PMID:163658", "title": "Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.", "content": "A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.", "contents": "Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies."} {"id": "PMID:163659", "title": "Hemoglobin J-Chicago (beta76(E20) Ala yields Asp): a new hemoglobin variant resulting from substitution of an external residue.", "content": "An electrophoretically fast-moving hemoglobin variant was found in a 2-yr-old boy who was referred for evaluation with findings of iron deficiency anemia. The anemia was corrected, and no hematologic abnormality remained after treatment with iron. Oxygen affinity of the blood was normal, and no evidence was found of instability of the variant hemoglobin. Structural studies demonstrated a substitution of aspartic acid for alanine at beta76 (E20). This change did not appear to cause any functional disruption of the hemoglobin in this patient, as would be predicted by the position of the affected animo acid residue on the surface of the molecule.", "contents": "Hemoglobin J-Chicago (beta76(E20) Ala yields Asp): a new hemoglobin variant resulting from substitution of an external residue. An electrophoretically fast-moving hemoglobin variant was found in a 2-yr-old boy who was referred for evaluation with findings of iron deficiency anemia. The anemia was corrected, and no hematologic abnormality remained after treatment with iron. Oxygen affinity of the blood was normal, and no evidence was found of instability of the variant hemoglobin. Structural studies demonstrated a substitution of aspartic acid for alanine at beta76 (E20). This change did not appear to cause any functional disruption of the hemoglobin in this patient, as would be predicted by the position of the affected animo acid residue on the surface of the molecule."} {"id": "PMID:163660", "title": "Mechanism of the protective effect of succinic semialdehyde and its derivatives in hypoxia.", "content": "Preliminary injection of succinic semialdehyde into animals in experiments with hypoxia led to a lower concentration of free ammonia in their brain tissues than in control experiments in which the compound was not given. The enzyme system of the liver tissue catalyzes the oxidation of NAD-H-2 by succinic semialdeyde and its dervitives with a free adelhyde group.The conversion of succinic semialdeyde and its derivatives in the liver tissue leading to the formation of the oxidized form of NAD,which is deficient in hypoxia, and the prevention of accumulation of free ammonia in the brain tissue by preliminary administration of succinic semialdehyde are the possible mechanisms of the antihypoxic properties of succinic semialdehyde and its derivatives.", "contents": "Mechanism of the protective effect of succinic semialdehyde and its derivatives in hypoxia. Preliminary injection of succinic semialdehyde into animals in experiments with hypoxia led to a lower concentration of free ammonia in their brain tissues than in control experiments in which the compound was not given. The enzyme system of the liver tissue catalyzes the oxidation of NAD-H-2 by succinic semialdeyde and its dervitives with a free adelhyde group.The conversion of succinic semialdeyde and its derivatives in the liver tissue leading to the formation of the oxidized form of NAD,which is deficient in hypoxia, and the prevention of accumulation of free ammonia in the brain tissue by preliminary administration of succinic semialdehyde are the possible mechanisms of the antihypoxic properties of succinic semialdehyde and its derivatives."} {"id": "PMID:163662", "title": "Ultrasound monitoring of hepatic metastases during chemotherapy.", "content": "Grey-scale ultrasonography has been found to be the most sensitive method of detecting metastatic disease of the liver. In two cases the results of chemotherapy were monitored by ultrasound; the response to treatment could be distinguished from non-response and ultrasonography gave useful information when chemotherapy made radioisotope examination unreliable.", "contents": "Ultrasound monitoring of hepatic metastases during chemotherapy. Grey-scale ultrasonography has been found to be the most sensitive method of detecting metastatic disease of the liver. In two cases the results of chemotherapy were monitored by ultrasound; the response to treatment could be distinguished from non-response and ultrasonography gave useful information when chemotherapy made radioisotope examination unreliable."} {"id": "PMID:163667", "title": "Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus.", "content": "When the entorhinal cortex is electrically stimulated, a monosynaptic evoked potential is produced in the ipsilateral hippocampus. Twenty-four hours after a 120-pulse stimulation train, the response to a single test pulse was found to be increased. Stimulation trains presented at a rate of 1/day had a cumulative effect on both the population EPSP and spike components of the evoked potential, and the potentiation so produced lasted at least 12 days. In a few cases, retested 2 months after the last stimulation train, the population EPSP was found to be still highly potentiated while the population spike had declined to initial levels. The most reliable results and largest potentiation were obtained with diphasic stimulation trains of 10 Hz or greater, though some changes were observed even with very low frequencies (0.2 Hz). The results imply that the efficiency of synaptic transmission in the perforant path-granule cell synapse can be modified.", "contents": "Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. When the entorhinal cortex is electrically stimulated, a monosynaptic evoked potential is produced in the ipsilateral hippocampus. Twenty-four hours after a 120-pulse stimulation train, the response to a single test pulse was found to be increased. Stimulation trains presented at a rate of 1/day had a cumulative effect on both the population EPSP and spike components of the evoked potential, and the potentiation so produced lasted at least 12 days. In a few cases, retested 2 months after the last stimulation train, the population EPSP was found to be still highly potentiated while the population spike had declined to initial levels. The most reliable results and largest potentiation were obtained with diphasic stimulation trains of 10 Hz or greater, though some changes were observed even with very low frequencies (0.2 Hz). The results imply that the efficiency of synaptic transmission in the perforant path-granule cell synapse can be modified."} {"id": "PMID:163668", "title": "Cellulase location in Cellvibrio fulvus.", "content": "The location of cellulase in C. fulvus depends on the carbon source for growth and the age of the culture. When cells were grown on glucose or cellobiose all CMC-hydrolyzing enzyme was cell-bound but only part of the activity was located on the cell surface. Treatment of cells with EDTA, lysozyme, and detergents and subsequent fractionation experiments showed that cellulase was also located in the periplasm and bound to a membrane fraction. Growth on cellulose gave cell-free cellulase active against CMC. The enzyme was repressed by glucose but formed at a constant differential rate on cellobiose and amylose. This rate was 8-10 times lower than on cellulose and possible reasons for this are discussed.", "contents": "Cellulase location in Cellvibrio fulvus. The location of cellulase in C. fulvus depends on the carbon source for growth and the age of the culture. When cells were grown on glucose or cellobiose all CMC-hydrolyzing enzyme was cell-bound but only part of the activity was located on the cell surface. Treatment of cells with EDTA, lysozyme, and detergents and subsequent fractionation experiments showed that cellulase was also located in the periplasm and bound to a membrane fraction. Growth on cellulose gave cell-free cellulase active against CMC. The enzyme was repressed by glucose but formed at a constant differential rate on cellobiose and amylose. This rate was 8-10 times lower than on cellulose and possible reasons for this are discussed."} {"id": "PMID:163670", "title": "Simplified procedures for releasing and concentrating microorganisms from soil for transmission electron microscopy viewing as thin-sectioned and frozen-etched preparations.", "content": "A simplified procedure is presented for releasing and concentrating indigenous microbial cells from soil for viewing by transmission electron microscopy as thin sections or replicas of frozen-etched preparations. This procedure is compared with two others reported earlier, and their relative merits are discussed as concerns the choice of procedure for the cellular information desired from the soil. Freeze-etching showed that the cell types and size distributions for cells which have been released and concentrated from soil are in general agreement with those for cells in a crude soil slurry in which no attempt to release and concentrate cells was made. Microcolonies were present both in the crude slurry and in the discard soil debris centrifugation pellets from the cell release and concentration procedures. In contrast to the historic assumptions, these microcolonies, as well as some individual cells embedded in soil debris could not be broken up and (or) dislodged so that they would be washed from the soil. The relative numbers of these cells remaining with the soil debris, however, could not be quantitated in the present study.", "contents": "Simplified procedures for releasing and concentrating microorganisms from soil for transmission electron microscopy viewing as thin-sectioned and frozen-etched preparations. A simplified procedure is presented for releasing and concentrating indigenous microbial cells from soil for viewing by transmission electron microscopy as thin sections or replicas of frozen-etched preparations. This procedure is compared with two others reported earlier, and their relative merits are discussed as concerns the choice of procedure for the cellular information desired from the soil. Freeze-etching showed that the cell types and size distributions for cells which have been released and concentrated from soil are in general agreement with those for cells in a crude soil slurry in which no attempt to release and concentrate cells was made. Microcolonies were present both in the crude slurry and in the discard soil debris centrifugation pellets from the cell release and concentration procedures. In contrast to the historic assumptions, these microcolonies, as well as some individual cells embedded in soil debris could not be broken up and (or) dislodged so that they would be washed from the soil. The relative numbers of these cells remaining with the soil debris, however, could not be quantitated in the present study."} {"id": "PMID:163671", "title": "The ultrastructure of the cellulolytic bacterium Cellvibrio fulvus.", "content": "Thin sections of the cellulolytic bacterium Cellvibrio fulvus were investigated before and after treatment with polymyxin B and Triton X-100. The Gram-negative vibrio appeared to have no separate stained g2 layer between the L and C membranes. Cells lysed after treatment with polymyxin or swelled in the presence of 5% sucrose. Blebs were formed from the L membrane, and the inner structure of the cells changed. Triton X-100 lysed cells even in the presence of 20% sucrose. The flagellum disappeared before lysis; one of the membranes was dissolved; and no organized inner structure could be seen.", "contents": "The ultrastructure of the cellulolytic bacterium Cellvibrio fulvus. Thin sections of the cellulolytic bacterium Cellvibrio fulvus were investigated before and after treatment with polymyxin B and Triton X-100. The Gram-negative vibrio appeared to have no separate stained g2 layer between the L and C membranes. Cells lysed after treatment with polymyxin or swelled in the presence of 5% sucrose. Blebs were formed from the L membrane, and the inner structure of the cells changed. Triton X-100 lysed cells even in the presence of 20% sucrose. The flagellum disappeared before lysis; one of the membranes was dissolved; and no organized inner structure could be seen."} {"id": "PMID:163672", "title": "Virusemenia after cytomegalovirus mononucleosis.", "content": "Cytomegalovirus (CMV) was demonstrated for 15 months in semen from a male homosexual with a recent history of a mononucleosis-like illness. The male urogenital tract can harbor CMV for long periods, and sexual transmission of the virus is more likely in persons with multiple heterosexual or homosexual contacts.", "contents": "Virusemenia after cytomegalovirus mononucleosis. Cytomegalovirus (CMV) was demonstrated for 15 months in semen from a male homosexual with a recent history of a mononucleosis-like illness. The male urogenital tract can harbor CMV for long periods, and sexual transmission of the virus is more likely in persons with multiple heterosexual or homosexual contacts."} {"id": "PMID:163673", "title": "A multiple chemotherapeutic approach to the management of hepatoblastoma. A preliminary report.", "content": "In 1970, a staging based on surgical resectability of hepatic tumors was devised. Adjuvant chemotherapy with vincristine, 5-fluorouracil, and cyclophosphamide has been given to seven recent cases. Objectives of this study were to set up unified clinical staging and followup; to evaluate the effect of combination chemotherapy on survival in advanced disease; and to evaluate early adjunctive combination chemotherapy in surgically resectable lesions to, hopefully, prevent metastasis. Results to date in seven patients are: no change in the poor prognosis of the three female patients presenting with Stage III-IV hepatocellular carcinoma; the three males with Stage I-II hepatoblastoma have done well and survive the free of disease at 47 months, 44 months, and 28 months; one patient with hepatoblastoma had lung metastasis at diagnosis and died at 7 months with tumor. No toxicity was noted with the use of adjunctive combination chemotherapy following major hepatic resection.", "contents": "A multiple chemotherapeutic approach to the management of hepatoblastoma. A preliminary report. In 1970, a staging based on surgical resectability of hepatic tumors was devised. Adjuvant chemotherapy with vincristine, 5-fluorouracil, and cyclophosphamide has been given to seven recent cases. Objectives of this study were to set up unified clinical staging and followup; to evaluate the effect of combination chemotherapy on survival in advanced disease; and to evaluate early adjunctive combination chemotherapy in surgically resectable lesions to, hopefully, prevent metastasis. Results to date in seven patients are: no change in the poor prognosis of the three female patients presenting with Stage III-IV hepatocellular carcinoma; the three males with Stage I-II hepatoblastoma have done well and survive the free of disease at 47 months, 44 months, and 28 months; one patient with hepatoblastoma had lung metastasis at diagnosis and died at 7 months with tumor. No toxicity was noted with the use of adjunctive combination chemotherapy following major hepatic resection."} {"id": "PMID:163675", "title": "A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213.", "content": "A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.", "contents": "A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP."} {"id": "PMID:163676", "title": "Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study.", "content": "Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.", "contents": "Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study. Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg."} {"id": "PMID:163677", "title": "Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management.", "content": "The clinicopathologic features of radiation enteritis are reviewed in 44 children receiving whole abdominal radiation therapy between 1961-1972 at the Institut Gustave-Roussy. Five of 14 long-term survivors (36%) developed severe delayed radiation injury with small bowel obstruction, occurring within 2 months after completion of irradiation. All had previously had acute radiation reaction during therapy. Histologic appearance in the small bowel at the time of delayed radiation injury revealed severe villus blunting, lymphatic dilatation, and moderately dense inflammatory infiltrate. All patients with delayed radiation injury showed marked clinical improvement coincident with a fractionated low-residue, low-fat diet, free of gluten and free of milk and milk products. The abnormal small bowel roentgenographs and small bowel biopsies reverted to a normal appearance in association with the diet. No exacerbation of radiation enteritis has been seen following dietary therapy.", "contents": "Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management. The clinicopathologic features of radiation enteritis are reviewed in 44 children receiving whole abdominal radiation therapy between 1961-1972 at the Institut Gustave-Roussy. Five of 14 long-term survivors (36%) developed severe delayed radiation injury with small bowel obstruction, occurring within 2 months after completion of irradiation. All had previously had acute radiation reaction during therapy. Histologic appearance in the small bowel at the time of delayed radiation injury revealed severe villus blunting, lymphatic dilatation, and moderately dense inflammatory infiltrate. All patients with delayed radiation injury showed marked clinical improvement coincident with a fractionated low-residue, low-fat diet, free of gluten and free of milk and milk products. The abnormal small bowel roentgenographs and small bowel biopsies reverted to a normal appearance in association with the diet. No exacerbation of radiation enteritis has been seen following dietary therapy."} {"id": "PMID:163678", "title": "Wilms' tumor and renal cell carcinoma in retroperitoneal teratoma.", "content": "A patient with a malignant retroperitoneal teratoma that contained Wilms' tumor and renal cell carcinoma is described. The rarity of renal tissue in teratoma, and the possible mode of development of Wilms' tumor and renal cell carcinoma in such a tumor are discussed.", "contents": "Wilms' tumor and renal cell carcinoma in retroperitoneal teratoma. A patient with a malignant retroperitoneal teratoma that contained Wilms' tumor and renal cell carcinoma is described. The rarity of renal tissue in teratoma, and the possible mode of development of Wilms' tumor and renal cell carcinoma in such a tumor are discussed."} {"id": "PMID:163679", "title": "Syndrome of fetal gigantism, renal hamartomas, and nephroblastomatosis with Wilms' tumor.", "content": "A new case of the fetal gigantism-renal hamartomas-nephroblastomatosis syndrome is described, in which a Wilms' tumor occurred. It is considered that this observation provides strong evidence for the interrelationship between renal dysplasia and renal neoplasia.", "contents": "Syndrome of fetal gigantism, renal hamartomas, and nephroblastomatosis with Wilms' tumor. A new case of the fetal gigantism-renal hamartomas-nephroblastomatosis syndrome is described, in which a Wilms' tumor occurred. It is considered that this observation provides strong evidence for the interrelationship between renal dysplasia and renal neoplasia."} {"id": "PMID:163680", "title": "Synovial sarcoma of the neck: a followup study of 24 cases.", "content": "This article reviews the clinicopathologic features and the biological behavior of 24 cases of synovial sarcoma that took origin from the cervical prevertebral connective tissue space and manifested as a retropharyngeal tumor or as a palpable mass in the anterior or posterior cervical triangle. The age of the 24 patients ranged from 10 to 51 years, with a median of 19 years. Ten patients were women and 14 men. Hoarseness or difficulty in breathing or swallowing were the first symptoms in eight patients. The tumors were solitary and ranged from 2 to 10 cm in greatest dimension. Microscopically, all of the cases showed the characteristic biphasic cellular pattern of a synovial sarcoma, with epithelioid and fibrosarcoma-like areas in varying proportions. Synovioblastic origin of the neoplasm was confirmed by the results of histochemical staining procedures and, in 1 case, by the examination with the electron microscope. Of the 21 cases followup information, 12 had died (10 with pulmonary metastasis) and 9 were alive and free of symptoms. Prompt and complete surgical removal is required to prevent complications from recurrent tumor growth or metastasis.", "contents": "Synovial sarcoma of the neck: a followup study of 24 cases. This article reviews the clinicopathologic features and the biological behavior of 24 cases of synovial sarcoma that took origin from the cervical prevertebral connective tissue space and manifested as a retropharyngeal tumor or as a palpable mass in the anterior or posterior cervical triangle. The age of the 24 patients ranged from 10 to 51 years, with a median of 19 years. Ten patients were women and 14 men. Hoarseness or difficulty in breathing or swallowing were the first symptoms in eight patients. The tumors were solitary and ranged from 2 to 10 cm in greatest dimension. Microscopically, all of the cases showed the characteristic biphasic cellular pattern of a synovial sarcoma, with epithelioid and fibrosarcoma-like areas in varying proportions. Synovioblastic origin of the neoplasm was confirmed by the results of histochemical staining procedures and, in 1 case, by the examination with the electron microscope. Of the 21 cases followup information, 12 had died (10 with pulmonary metastasis) and 9 were alive and free of symptoms. Prompt and complete surgical removal is required to prevent complications from recurrent tumor growth or metastasis."} {"id": "PMID:163681", "title": "Specific estrogen binding in rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene.", "content": "Experiments were undertaken with 7,12-dimethylbenz(q)anthracene-induced mammary tumors of the rat to determine whether ovarian-dependent and ovarian-independent tumors could be distinguished on the basis of differences in the estrogen binding capacity of the tumors in vitro and in vivo. Our results confirm reports showing that ovarian-depentent tumors undergo interaction between ovarian-dependent tumors undergo interaction between 17beta-(3H)estradiol and specific estrogen binding components both in vivo and in vitro, as described for other estrogen target tissues. However, our results also demonstrated that certain 7,12-dimethylbenz(a)anthracene-induced tumors, which continue to grow after ovariectomy of the host, contained significant amounts of 17beta-(3H)estradiol bound to cytoplasmic as well as nuclear components. The sedimentation properties of these components were indistinguishable from those of either ovarian-dependent 7,12-dimethylbenz(a)anthracene-induced tumors or rat uterus. The cytoplasmic binding components of both classes of tumors exhibited similar specificities for estrogens. There did not appear to be an absolute correlation between estrogen-binding capacity of a tumor and its growth response to ovariectomy.", "contents": "Specific estrogen binding in rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. Experiments were undertaken with 7,12-dimethylbenz(q)anthracene-induced mammary tumors of the rat to determine whether ovarian-dependent and ovarian-independent tumors could be distinguished on the basis of differences in the estrogen binding capacity of the tumors in vitro and in vivo. Our results confirm reports showing that ovarian-depentent tumors undergo interaction between ovarian-dependent tumors undergo interaction between 17beta-(3H)estradiol and specific estrogen binding components both in vivo and in vitro, as described for other estrogen target tissues. However, our results also demonstrated that certain 7,12-dimethylbenz(a)anthracene-induced tumors, which continue to grow after ovariectomy of the host, contained significant amounts of 17beta-(3H)estradiol bound to cytoplasmic as well as nuclear components. The sedimentation properties of these components were indistinguishable from those of either ovarian-dependent 7,12-dimethylbenz(a)anthracene-induced tumors or rat uterus. The cytoplasmic binding components of both classes of tumors exhibited similar specificities for estrogens. There did not appear to be an absolute correlation between estrogen-binding capacity of a tumor and its growth response to ovariectomy."} {"id": "PMID:163682", "title": "Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer.", "content": "Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer.", "contents": "Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer. Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer."} {"id": "PMID:163683", "title": "The glycosaminoglycans in human hepatic cancer.", "content": "A method is proposed for the analysis of glycosaminoglycans that were isolated from human liver, combining cellulose acetate electrophoresis and enzymatic digestion with mucopolysaccharidases. The major constituent of glycossaminoglycans in the healthy liver is heparin sulfate and/or heparin (about 65%), with approximately equal quantities of dermatan sulfate and hyalauronic acid (about 13.5 and 13%, respectively) and a small amount of chondroitin sulfate. These components, especially chondroitin sulfate and hyaluronic acid, are markedly increased in hepatic carcinomas.", "contents": "The glycosaminoglycans in human hepatic cancer. A method is proposed for the analysis of glycosaminoglycans that were isolated from human liver, combining cellulose acetate electrophoresis and enzymatic digestion with mucopolysaccharidases. The major constituent of glycossaminoglycans in the healthy liver is heparin sulfate and/or heparin (about 65%), with approximately equal quantities of dermatan sulfate and hyalauronic acid (about 13.5 and 13%, respectively) and a small amount of chondroitin sulfate. These components, especially chondroitin sulfate and hyaluronic acid, are markedly increased in hepatic carcinomas."} {"id": "PMID:163684", "title": "Blastomogenic activity of p-hydroxyphenyllactic acid in mice.", "content": "Blastomogenic activity of p-hydroxyphenyllactic acid was established by prolonged s.c. administration into C57BL/6 and CC57BR mice. Phenyllactic acid was also tested and was not blastomogenic under the same conditions. The preparations in aqueous solutions were injected into the dorsal region twice weekly in 1.5-mg doses. The total dose per mouse was 42 mg p-hydroxyphenyllactic acid or 50 mg phenyllactic acid. The resorptive character and many forms of blastomogenic activity of p-hydroxphenyllactic acid were shown. It induced neoplasms of varied histogenesis (leukemias, adenomas, hepatomas, and tumors of the vascular tissue),including benign and malignant tumors and precancerous conditions of the urniary bladder.", "contents": "Blastomogenic activity of p-hydroxyphenyllactic acid in mice. Blastomogenic activity of p-hydroxyphenyllactic acid was established by prolonged s.c. administration into C57BL/6 and CC57BR mice. Phenyllactic acid was also tested and was not blastomogenic under the same conditions. The preparations in aqueous solutions were injected into the dorsal region twice weekly in 1.5-mg doses. The total dose per mouse was 42 mg p-hydroxyphenyllactic acid or 50 mg phenyllactic acid. The resorptive character and many forms of blastomogenic activity of p-hydroxphenyllactic acid were shown. It induced neoplasms of varied histogenesis (leukemias, adenomas, hepatomas, and tumors of the vascular tissue),including benign and malignant tumors and precancerous conditions of the urniary bladder."} {"id": "PMID:163685", "title": "Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h).", "content": "Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.", "contents": "Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h). Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations."} {"id": "PMID:163686", "title": "Increased activity of low-Km cyclic adenosine 3':5'-monophosphate phosphodiesterase in plasma membranes of Morris hepatoma 5123tc (h).", "content": "The total cyclic adenosine 3':5'-monophosphate (cAMP) phosphodiesterase activities as well as the activities of the low- and high-K-m enzyme forms were investigated in homogenates, 100,000 X g supernatants, and plasma membrane fractions of rat liver and Morris hepatoma 5123tc(h); the responsiveness of hepatoma and liver plasma membrane (low-K-m) phosphodiesterases to imidazole (40 mM) and theophylline (5mM) were also compared at cAMP concentrations of 1 and 7.5 muM. The total cAMP phosphodiesterase activities of tumor homogenates and 100,000 X g supernatant fractions were found to be less than one-half those of liver; kinetic studies of homogenates indicated that this finding was largely due to a substantial reduction (53%) in activity of the hepatoma high-K-m enzyme. In contrast, low-Km cAMP phosphodiesterase activities for tumor homogenate and plasma membrane fractions were significantly (50%) higher than liver; this was particularly evident when cAMP concentrations were between 0.5 and 2 muM. Since these concentrations are in the range of basal physiological levels of cAMP in hepatocytes, the present results suggest that the reduced levels of cAMP, previously observed in hepatoma 5123tc (h), are primarily due TO An increased rate of cAMP metabolism by low-Km cAMP phosphodiesterase in plasma membranes of the tumor. Imidazole increased the activity of the low-K-m cAMP phosphodiesterase of liver plasma membranes by 22 (1 muM cAMP) and 38% (7.5 muM camp); tumor activity was enhanced 35 and 50%, respectively, at 1 and 7.5 muM cAMP. Theophylline inhibited the plasma membrane phosphodiesterase activity of liver 79 and 53% at cAMP concentrations of 1 and 7.5 muM, respectively; hepatoma activity was inhibited 82 (1 muM cAMP) and 62% (7.5 muM cAMP).", "contents": "Increased activity of low-Km cyclic adenosine 3':5'-monophosphate phosphodiesterase in plasma membranes of Morris hepatoma 5123tc (h). The total cyclic adenosine 3':5'-monophosphate (cAMP) phosphodiesterase activities as well as the activities of the low- and high-K-m enzyme forms were investigated in homogenates, 100,000 X g supernatants, and plasma membrane fractions of rat liver and Morris hepatoma 5123tc(h); the responsiveness of hepatoma and liver plasma membrane (low-K-m) phosphodiesterases to imidazole (40 mM) and theophylline (5mM) were also compared at cAMP concentrations of 1 and 7.5 muM. The total cAMP phosphodiesterase activities of tumor homogenates and 100,000 X g supernatant fractions were found to be less than one-half those of liver; kinetic studies of homogenates indicated that this finding was largely due to a substantial reduction (53%) in activity of the hepatoma high-K-m enzyme. In contrast, low-Km cAMP phosphodiesterase activities for tumor homogenate and plasma membrane fractions were significantly (50%) higher than liver; this was particularly evident when cAMP concentrations were between 0.5 and 2 muM. Since these concentrations are in the range of basal physiological levels of cAMP in hepatocytes, the present results suggest that the reduced levels of cAMP, previously observed in hepatoma 5123tc (h), are primarily due TO An increased rate of cAMP metabolism by low-Km cAMP phosphodiesterase in plasma membranes of the tumor. Imidazole increased the activity of the low-K-m cAMP phosphodiesterase of liver plasma membranes by 22 (1 muM cAMP) and 38% (7.5 muM camp); tumor activity was enhanced 35 and 50%, respectively, at 1 and 7.5 muM cAMP. Theophylline inhibited the plasma membrane phosphodiesterase activity of liver 79 and 53% at cAMP concentrations of 1 and 7.5 muM, respectively; hepatoma activity was inhibited 82 (1 muM cAMP) and 62% (7.5 muM cAMP)."} {"id": "PMID:163687", "title": "Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthracene-induced tumors.", "content": "Hormonal influences on dimethylbenz(a)anthracene-induced tumor growth were investigated in detail by endocrine ablation and replacement of hormones. The majority of tumors regressed following ablation and most of them were reactivated by subsequent administrations of estrogen (0.1 to 5 mug) or prolactin (2 mg). Increasing numbers of tumors, however, were not stimulated by prolactin when administration was delayed, and a basal level of estradiol (0.01 mug) in addition to prolactin was required for reactivation of tumors. Nafoxidine hydrochloride, a competitor of estrogen at the receptor sites, arrested growth of a large portion of dimethylbenz(a)anthracene-induced tumors in intact animals but failed to retard growth of prolactin-stimulated tumors. On withdrawal of prolactin-nafoxidine, rapid regression of tumor occurred and readministration of prolactin failed to activate most of the tumors for as long as 28 days. Our results give good supporting evidence that estrogen plays a primary role in tumor growth. The interactions of prolactin and estrogen at tumor sites are necessary for regulatory events related to tumor growth.", "contents": "Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthracene-induced tumors. Hormonal influences on dimethylbenz(a)anthracene-induced tumor growth were investigated in detail by endocrine ablation and replacement of hormones. The majority of tumors regressed following ablation and most of them were reactivated by subsequent administrations of estrogen (0.1 to 5 mug) or prolactin (2 mg). Increasing numbers of tumors, however, were not stimulated by prolactin when administration was delayed, and a basal level of estradiol (0.01 mug) in addition to prolactin was required for reactivation of tumors. Nafoxidine hydrochloride, a competitor of estrogen at the receptor sites, arrested growth of a large portion of dimethylbenz(a)anthracene-induced tumors in intact animals but failed to retard growth of prolactin-stimulated tumors. On withdrawal of prolactin-nafoxidine, rapid regression of tumor occurred and readministration of prolactin failed to activate most of the tumors for as long as 28 days. Our results give good supporting evidence that estrogen plays a primary role in tumor growth. The interactions of prolactin and estrogen at tumor sites are necessary for regulatory events related to tumor growth."} {"id": "PMID:163688", "title": "Alteration of glycine N-methyltransferase activity in fetal, adult, and tumor tissues.", "content": "Glycine N-methyltransferase activity has been examined in a number of fetal and adult organs, as well as in several rodent hepatomas, using both enzymatic and immunological techniques. In fetal rabbit liver, the activity first appears at a low level at about 20 days postfertilization and rises to high levels after birth, reaching maximum in the adult liver. In fast-growing hepatomas, the activity could not be detected by either enzymatic or immunological assay. It could be detected in the slower-growing hepatomas, but in considerably diminished levels compared with that of normal adult rat liver. Immunoassays gave no evidence for inactive forms of the enzyme in the tissues that had no enzymatic activity. Transfer RNA methyltransferase assays carried out simultaneously showed an inverse relationship to the glycine N-methyltransferase activity. The levels of transfer RNA methyltransferase activity were high in fetal and tumor tissues and lower in normal adult tissues.", "contents": "Alteration of glycine N-methyltransferase activity in fetal, adult, and tumor tissues. Glycine N-methyltransferase activity has been examined in a number of fetal and adult organs, as well as in several rodent hepatomas, using both enzymatic and immunological techniques. In fetal rabbit liver, the activity first appears at a low level at about 20 days postfertilization and rises to high levels after birth, reaching maximum in the adult liver. In fast-growing hepatomas, the activity could not be detected by either enzymatic or immunological assay. It could be detected in the slower-growing hepatomas, but in considerably diminished levels compared with that of normal adult rat liver. Immunoassays gave no evidence for inactive forms of the enzyme in the tissues that had no enzymatic activity. Transfer RNA methyltransferase assays carried out simultaneously showed an inverse relationship to the glycine N-methyltransferase activity. The levels of transfer RNA methyltransferase activity were high in fetal and tumor tissues and lower in normal adult tissues."} {"id": "PMID:163689", "title": "Identification of the virions in the in vitro L1210(V) leukemia cell lines by morphological, virological, and immunological techniques.", "content": "In vitro L1210 (V) cell lines contained abundant intracytoplasmic A-particles, numerous C-type particles, a small number of B-type particles, and occasional intracisternal A-particles. The intracytoplasmic A-particles were incorporated into both spiked (B-type) and smooth-surfaced (C-type) particles formed at the budding site. Both B-and C-type particles also developed by gradual accululation of neucleooid material. The particles, particularly the C-type, exhibited a wide range of densities. The cells showed strong surface immunofluoresence for both murine mammary tumor virus and Gross murine leukemia virus antigens and variable degrees of cytoplasmic immunoflurescence for the protein antigens (p1 to p6) of Rauscher leukemia virus. The cells, the culture supernatant, and the purified virus each gave positive reactions with murine mammary tumor virus and murine leukemia virus antisera by immunodiffusion. The viral particles failed to infect C57BL, C57BL/6 X DBA/2F1 (hereafter called BD2F1), BALB/c, Af,and RIIIf mice. Howver, the cells were highly tumorigenic in BD1F-1 mice, moderately tumorigenic in BALB/c mice, but not tumorigenic in C57BL, Af, and RIIIf mice.", "contents": "Identification of the virions in the in vitro L1210(V) leukemia cell lines by morphological, virological, and immunological techniques. In vitro L1210 (V) cell lines contained abundant intracytoplasmic A-particles, numerous C-type particles, a small number of B-type particles, and occasional intracisternal A-particles. The intracytoplasmic A-particles were incorporated into both spiked (B-type) and smooth-surfaced (C-type) particles formed at the budding site. Both B-and C-type particles also developed by gradual accululation of neucleooid material. The particles, particularly the C-type, exhibited a wide range of densities. The cells showed strong surface immunofluoresence for both murine mammary tumor virus and Gross murine leukemia virus antigens and variable degrees of cytoplasmic immunoflurescence for the protein antigens (p1 to p6) of Rauscher leukemia virus. The cells, the culture supernatant, and the purified virus each gave positive reactions with murine mammary tumor virus and murine leukemia virus antisera by immunodiffusion. The viral particles failed to infect C57BL, C57BL/6 X DBA/2F1 (hereafter called BD2F1), BALB/c, Af,and RIIIf mice. Howver, the cells were highly tumorigenic in BD1F-1 mice, moderately tumorigenic in BALB/c mice, but not tumorigenic in C57BL, Af, and RIIIf mice."} {"id": "PMID:163690", "title": "A comparison of the effects of daunomycin and adriamycin on various DNA polymerases.", "content": "The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory effect against the viral polymerase than against cellular polymerase. The inhibition of murine sarcoma virus DNA polymerase by daunomycin was competitive with respect to DNA. For viral DNA polymerase it was concluded that the inhibition was predominatly caused by the interaction of duanomycin with the primer-template DNA. Also, an appreciable reversal of the daunomycin-induced inhibition of this polymerase by an increase in Mg-2+ concentration is consistent with the conclusion derived by competition experiments. In contrast, the inhibition of both rat liver and M. luteus DNA polymerases was essentially noncompetitive with DNA. Also, bacterial enzymes wer e less sensitive to inhibition by these drugs than the virion polymerase. The strong and preferential inhibiton of viral DNA polymerase is discussed in relation to a differential sensitivity of normal as compared to tumor cells observed in some cell lines.", "contents": "A comparison of the effects of daunomycin and adriamycin on various DNA polymerases. The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory effect against the viral polymerase than against cellular polymerase. The inhibition of murine sarcoma virus DNA polymerase by daunomycin was competitive with respect to DNA. For viral DNA polymerase it was concluded that the inhibition was predominatly caused by the interaction of duanomycin with the primer-template DNA. Also, an appreciable reversal of the daunomycin-induced inhibition of this polymerase by an increase in Mg-2+ concentration is consistent with the conclusion derived by competition experiments. In contrast, the inhibition of both rat liver and M. luteus DNA polymerases was essentially noncompetitive with DNA. Also, bacterial enzymes wer e less sensitive to inhibition by these drugs than the virion polymerase. The strong and preferential inhibiton of viral DNA polymerase is discussed in relation to a differential sensitivity of normal as compared to tumor cells observed in some cell lines."} {"id": "PMID:163691", "title": "Heritability of the phytohemagglutinin responsiveness of lymphocytes and its relationship to leukemogenesis.", "content": "Upon analyses of 59 inbred strains, F-1 hybrids, and congenic-resistant mouse strains, the strain distribution pattern of the stimulation of perippheral mouse lymphocytes by phytohemagglutinin was established using a micromethod. The family of DBA mice were the lowest responders of phytohemagglutinin, whereas the C57 family responded best. Strain PL/J exhibited the best response. The response of lymphocytes to the lectin is governed by more than two but less than five major genes of unknown linkage. No direct association to the H-2 histocompatibility complex was found, although an indirect influence of this locus could not be excluded. All high-leukemia strains are good responders to phytohemagglutinin. None of the low-responder-group strains exhibit spontaneous leukemia. No correlation of the response of lymphocytes to the expression of the type C RNA genome could be established. Cell suspensions from animals exhibiting clinical signs of leukemia responded only weakly or not all to the lectin.", "contents": "Heritability of the phytohemagglutinin responsiveness of lymphocytes and its relationship to leukemogenesis. Upon analyses of 59 inbred strains, F-1 hybrids, and congenic-resistant mouse strains, the strain distribution pattern of the stimulation of perippheral mouse lymphocytes by phytohemagglutinin was established using a micromethod. The family of DBA mice were the lowest responders of phytohemagglutinin, whereas the C57 family responded best. Strain PL/J exhibited the best response. The response of lymphocytes to the lectin is governed by more than two but less than five major genes of unknown linkage. No direct association to the H-2 histocompatibility complex was found, although an indirect influence of this locus could not be excluded. All high-leukemia strains are good responders to phytohemagglutinin. None of the low-responder-group strains exhibit spontaneous leukemia. No correlation of the response of lymphocytes to the expression of the type C RNA genome could be established. Cell suspensions from animals exhibiting clinical signs of leukemia responded only weakly or not all to the lectin."} {"id": "PMID:163692", "title": "Benzo(alpha)pyrene effects on mouse epithelial cells in culture.", "content": "The effect of benzo (a) pyrene on the growth in culture of 5 mouse epithelial cell strains was examined. These epithelial cells are highly sensitive to the cytotoxic action of benzo (a)-pyrene. In addition, the activity of the benzol (a) pyrene-metabolizing system, aryl hydrocarbon hydroxylase, is low but highly iducible by the carcinogen. As the sensitivity of a cell strain to the cytotoxic action of benjo (a) pyrene decreased, the inudcibility of the hydroxylase also decreased,. However, a strong correlation could not be found between cytotoxicity and the level of uninduced or induced hydroxylase when the values from different cell strains were compared. These experiments suggest that thehydroxylase is important in determining the sensitivity of epithelial cells to the cytotoxic action of benzo (a) pyrene, but other factors may also modulate this sensitivity.", "contents": "Benzo(alpha)pyrene effects on mouse epithelial cells in culture. The effect of benzo (a) pyrene on the growth in culture of 5 mouse epithelial cell strains was examined. These epithelial cells are highly sensitive to the cytotoxic action of benzo (a)-pyrene. In addition, the activity of the benzol (a) pyrene-metabolizing system, aryl hydrocarbon hydroxylase, is low but highly iducible by the carcinogen. As the sensitivity of a cell strain to the cytotoxic action of benjo (a) pyrene decreased, the inudcibility of the hydroxylase also decreased,. However, a strong correlation could not be found between cytotoxicity and the level of uninduced or induced hydroxylase when the values from different cell strains were compared. These experiments suggest that thehydroxylase is important in determining the sensitivity of epithelial cells to the cytotoxic action of benzo (a) pyrene, but other factors may also modulate this sensitivity."} {"id": "PMID:163693", "title": "Peptidyl proline hydroxylase in adult, developing, and neoplastic rat tissues.", "content": "A sensitive assay system, optimally supplemented with tritiated protocollagen substrate and cofactors, is described which is suitable for determining the peptidyl proline hydroxylase (PPH) content of a wide spectrum of rat tissues. In most tissues, less than 50 percent of the total activity was soluble; the particulate portion of the activity (concentrated in the mitochondrial and microsomal fractions) was doubled by pretreatment with Triton X-100. Among normal adult tissues, lung had the highest total PPH activity (2.4 times that of liver) and small intestine had the lowest (25 percent that of liver). In brain and lactating mammary gland, the activity was similar to that in skin (60 percent of that in liver). Fetal tissues contained 3 to 8 times more PPH than the corresponding adult tissues, and a much lower portion of the total activity was soluble. In four tissues studied in detail (lung, liver, kidney, and brain), the total PPH declined rapidly during the last few days of gestation; brain attained its low adult value before term, whereas the other three tissues continued to decrease in the course of postnatal development. An injection of cortisol to fetal rats enhanced the decline of PPH in lung, liver, and skull. These experiments suggest that during normal differentiation the decline in collagen synthesis is initiated by fetal glucocorticoid secretion which is maximal on the 19th gestational day. PPH activity appears to be a sensitive indicator of neoplastic growth. In renal, mammary, muscle, and hepatic tumors, the PPH activities were 4 to 10 times higher than in the cognate adult tissue. Even in well-differentiated, slowgrowing tumors, the activity was considerably higher than in any normal, mature, or immature tissue, with the exception of the skull and lung of the 19-day-old fetus.", "contents": "Peptidyl proline hydroxylase in adult, developing, and neoplastic rat tissues. A sensitive assay system, optimally supplemented with tritiated protocollagen substrate and cofactors, is described which is suitable for determining the peptidyl proline hydroxylase (PPH) content of a wide spectrum of rat tissues. In most tissues, less than 50 percent of the total activity was soluble; the particulate portion of the activity (concentrated in the mitochondrial and microsomal fractions) was doubled by pretreatment with Triton X-100. Among normal adult tissues, lung had the highest total PPH activity (2.4 times that of liver) and small intestine had the lowest (25 percent that of liver). In brain and lactating mammary gland, the activity was similar to that in skin (60 percent of that in liver). Fetal tissues contained 3 to 8 times more PPH than the corresponding adult tissues, and a much lower portion of the total activity was soluble. In four tissues studied in detail (lung, liver, kidney, and brain), the total PPH declined rapidly during the last few days of gestation; brain attained its low adult value before term, whereas the other three tissues continued to decrease in the course of postnatal development. An injection of cortisol to fetal rats enhanced the decline of PPH in lung, liver, and skull. These experiments suggest that during normal differentiation the decline in collagen synthesis is initiated by fetal glucocorticoid secretion which is maximal on the 19th gestational day. PPH activity appears to be a sensitive indicator of neoplastic growth. In renal, mammary, muscle, and hepatic tumors, the PPH activities were 4 to 10 times higher than in the cognate adult tissue. Even in well-differentiated, slowgrowing tumors, the activity was considerably higher than in any normal, mature, or immature tissue, with the exception of the skull and lung of the 19-day-old fetus."} {"id": "PMID:163694", "title": "Comparison of the immunogenicity of hamster cells transformed by adenovirus and Herpes simplex virus.", "content": "Hamsters vaccinated with adenovirus-transformed cells, modified by acetoacetylation or concanavalin A treatment, or with small numbers of living cells were partly or completely protected against challenge with 3 times 10-6 living cells. Treatment of vaccine cells with iodoacetate, Mitomycin C, neuraminidase plus Mitomycin C did not produce efficient vaccines. Herpes simplex virus-transformed cells treated by any of these procedures did not prevent, and frequently even enhanced, the growth of the homologous living cells; enhancement was often greater in female than in male hamsters. Protective and enhancing vaccines did not induce a different level of cell-mediated immunity, as detected by lymphocytotoxicity tests, which were positive for both homologous transformed cells and nontransformed hamster cells. In contrast, specific complement-dependent cytotoxic antibodies active only on adenovirus-transformed cells were induced by the protective acetoacetylated vaccine prepared from adenovirus-transformed cells; these antibodies were not present after nonprotective vaccinations. The appearance of herpes simplex virus tumors was delayed by treatment with the immunostimulant, Levamisole, or by preimmunization with Newcastle disease virus grown in SV40-transformed cells, but not by Newcastle disease virus grown in herpes simplex virus-transformed cells. Thus, only nonspecific treatments were able to impede herpes simplex virus tumor growth, while protection against adenovirus tumor was accompanied by specific cytotoxic antibodies.", "contents": "Comparison of the immunogenicity of hamster cells transformed by adenovirus and Herpes simplex virus. Hamsters vaccinated with adenovirus-transformed cells, modified by acetoacetylation or concanavalin A treatment, or with small numbers of living cells were partly or completely protected against challenge with 3 times 10-6 living cells. Treatment of vaccine cells with iodoacetate, Mitomycin C, neuraminidase plus Mitomycin C did not produce efficient vaccines. Herpes simplex virus-transformed cells treated by any of these procedures did not prevent, and frequently even enhanced, the growth of the homologous living cells; enhancement was often greater in female than in male hamsters. Protective and enhancing vaccines did not induce a different level of cell-mediated immunity, as detected by lymphocytotoxicity tests, which were positive for both homologous transformed cells and nontransformed hamster cells. In contrast, specific complement-dependent cytotoxic antibodies active only on adenovirus-transformed cells were induced by the protective acetoacetylated vaccine prepared from adenovirus-transformed cells; these antibodies were not present after nonprotective vaccinations. The appearance of herpes simplex virus tumors was delayed by treatment with the immunostimulant, Levamisole, or by preimmunization with Newcastle disease virus grown in SV40-transformed cells, but not by Newcastle disease virus grown in herpes simplex virus-transformed cells. Thus, only nonspecific treatments were able to impede herpes simplex virus tumor growth, while protection against adenovirus tumor was accompanied by specific cytotoxic antibodies."} {"id": "PMID:163695", "title": "Evaluation of irradiation-plus-urethan-induced murine leukemia virus \"release\" using a new method for quantitation of oncornaviruses in tissues.", "content": "The quantity of C-type RNA tumor viruses in homogenate-sonicates of thymus-bone marrow tissues of C57BL/6J and RFM/Un mice 10 days after irradiation (X-rays or gamma-rays)-plus-urethan treatments is no greater than that in thymus-bone marrow homogenates from nontreated control mice. These results indicate that the leukemogenic activity, shown to be present in such thymus-bone marrow homogenates at this time after irradiation-plus-urethan treatment, is not due to change in quantity of C-type viruses as has been proposed. Virus quantity in tissues was evaluated by a new procedure that includes use of a microchamber with the sides situated on rotor radii so as to produce a uniform virus-containing sediment of tissue homogenate-sonicate that is evaluated by electron microscopic examination of this sections cut perpendicular to the membrane surface. Samples containing as little as 105 to 106 viruses can be relatively easily counted. Semipurified or purified viruses can also be counted after mixing with a tissue homogenate-bovine serum albumin diluent.", "contents": "Evaluation of irradiation-plus-urethan-induced murine leukemia virus \"release\" using a new method for quantitation of oncornaviruses in tissues. The quantity of C-type RNA tumor viruses in homogenate-sonicates of thymus-bone marrow tissues of C57BL/6J and RFM/Un mice 10 days after irradiation (X-rays or gamma-rays)-plus-urethan treatments is no greater than that in thymus-bone marrow homogenates from nontreated control mice. These results indicate that the leukemogenic activity, shown to be present in such thymus-bone marrow homogenates at this time after irradiation-plus-urethan treatment, is not due to change in quantity of C-type viruses as has been proposed. Virus quantity in tissues was evaluated by a new procedure that includes use of a microchamber with the sides situated on rotor radii so as to produce a uniform virus-containing sediment of tissue homogenate-sonicate that is evaluated by electron microscopic examination of this sections cut perpendicular to the membrane surface. Samples containing as little as 105 to 106 viruses can be relatively easily counted. Semipurified or purified viruses can also be counted after mixing with a tissue homogenate-bovine serum albumin diluent."} {"id": "PMID:163696", "title": "A mixed-immunoglobulin rosette technique for detection of antibody to feline oncornavirus-associated cell membrane antigen.", "content": "A mixed-immunoglobulin rosette technique has been developed for the detection of antibodies to feline oncornavirus-associated cell membrane antigens. Lymphoblastoid cells infected with feline leukemia virus were incubated with test sera and then fixed in paraformaldehyde. They were then exposed to a rabbit anti-cat immunoglobulin G serum. Antigen-antibody reactions were detected by mixing the cells with sheep erythrocytes sensitized with cat anti-sheep red blood cell serum; the presence of cat antibody on the lymphoid cells was registered by the formation of sheep red blood cell rosettes around them. The method was shown to be at least 10 times more sensitive than indirect immunofluorescence. A high degree of correlation was shown between the mixed-immunoglobulin rosette and indirect immunofluorescence tests, using both feline leukemia virus-infected cat and dog cells as targets. The results indicate that the tests are likely to be measuring similar reactions. Using the indirect immunofluorescence test we found that 75% of cats with lymphoid neoplasia had no demonstrable antibodies. Twenty-four of such indirect immunofluorescence-negative sera were tested by the mixed-immunoglobulin rosette technique; antibody was shown in at least seven of these sera.", "contents": "A mixed-immunoglobulin rosette technique for detection of antibody to feline oncornavirus-associated cell membrane antigen. A mixed-immunoglobulin rosette technique has been developed for the detection of antibodies to feline oncornavirus-associated cell membrane antigens. Lymphoblastoid cells infected with feline leukemia virus were incubated with test sera and then fixed in paraformaldehyde. They were then exposed to a rabbit anti-cat immunoglobulin G serum. Antigen-antibody reactions were detected by mixing the cells with sheep erythrocytes sensitized with cat anti-sheep red blood cell serum; the presence of cat antibody on the lymphoid cells was registered by the formation of sheep red blood cell rosettes around them. The method was shown to be at least 10 times more sensitive than indirect immunofluorescence. A high degree of correlation was shown between the mixed-immunoglobulin rosette and indirect immunofluorescence tests, using both feline leukemia virus-infected cat and dog cells as targets. The results indicate that the tests are likely to be measuring similar reactions. Using the indirect immunofluorescence test we found that 75% of cats with lymphoid neoplasia had no demonstrable antibodies. Twenty-four of such indirect immunofluorescence-negative sera were tested by the mixed-immunoglobulin rosette technique; antibody was shown in at least seven of these sera."} {"id": "PMID:163697", "title": "The regulation of serine dehydratase and glucose-6-phosphatase in hyperplastic nodules of rat liver during diethylnitrosamine and N-2-fluorenylacetamide feeding.", "content": "Changes in the levels of serine dehydratase and glucose-6-phosphatase induced by dietary stimuli or starvation in hyperplastic nodules of rat liver during diethylnitrosamine or N-2-fluorenylacetamide feeding were studied by immuno- and enzyme histochemical methods. The study was performed during carcinogenesis through a combined method of enzyme histochemistry and radioautography. Serine dehydratase was observed diffusely in the cytoplasm of the original hepatocytes in the periportal zone and was induced markedly during diethynitrosamine feeding but only slightly during N-2-fluorenylacetamide feeding. The enzyme was deficient and not inducible in hyperplastic nodules during their developing phase. Later during the feeding period, however, there was an elevation of the level of serine dehydratase and its inducibility with time in the majority of the nodules. A good correlation was observed between serine dehydratase and glucose-6-phosphatase in their elevated levels and response to enviornmental stimuli. There was a minor group of hyperplastic nodules in which the deficiencies of these enzymes persisted and enzyme induction was not observed. A greater number of hyperplastic nodules with persistent enzyme deficiency was seen during diethylnitrosamine carcinogenesis. These results provide further information about the changing biological nature of hyperplastic nodules with respect to their metabolic adaptability and enzyme levels during hepatocarcinogenesis.", "contents": "The regulation of serine dehydratase and glucose-6-phosphatase in hyperplastic nodules of rat liver during diethylnitrosamine and N-2-fluorenylacetamide feeding. Changes in the levels of serine dehydratase and glucose-6-phosphatase induced by dietary stimuli or starvation in hyperplastic nodules of rat liver during diethylnitrosamine or N-2-fluorenylacetamide feeding were studied by immuno- and enzyme histochemical methods. The study was performed during carcinogenesis through a combined method of enzyme histochemistry and radioautography. Serine dehydratase was observed diffusely in the cytoplasm of the original hepatocytes in the periportal zone and was induced markedly during diethynitrosamine feeding but only slightly during N-2-fluorenylacetamide feeding. The enzyme was deficient and not inducible in hyperplastic nodules during their developing phase. Later during the feeding period, however, there was an elevation of the level of serine dehydratase and its inducibility with time in the majority of the nodules. A good correlation was observed between serine dehydratase and glucose-6-phosphatase in their elevated levels and response to enviornmental stimuli. There was a minor group of hyperplastic nodules in which the deficiencies of these enzymes persisted and enzyme induction was not observed. A greater number of hyperplastic nodules with persistent enzyme deficiency was seen during diethylnitrosamine carcinogenesis. These results provide further information about the changing biological nature of hyperplastic nodules with respect to their metabolic adaptability and enzyme levels during hepatocarcinogenesis."} {"id": "PMID:163698", "title": "Physicochemical characterization of Novikoff hepatoma mitochondrial DNA.", "content": "Mitochondrial DNA's (mtDNA) isolated from rat liver and the Novikoff hepatoma grown as both solid tumors and cells in monolayer culture were examined by a variety of physicochemical techniques. Buoyant densities in analytical CsCl equilibrium gradients and thermal denaturation profiles revealed no significant differences in base composition among the mtDNA's isolated from liver, tumor, and hepatoma cells. Sedimentation in neurtral and alkaline CsCl showed no differences in mtDNA size. However, tumor and hepatoma cell mtDNA's were slightly smaller and more heterogeneous in size than liver mtDNA when molecular contour lengths were measured in the electron microscope. Based on chemical determinations, neoplastic mitochondria contained four to five times more DNA per mitochondrion than liver. Also, electron microscopy showed the proportion of mtDNA in complex forms (catenated dimers and oligomers) to be much higher in tumor (18%) and hepatoma cells (15%) than liver (4%).", "contents": "Physicochemical characterization of Novikoff hepatoma mitochondrial DNA. Mitochondrial DNA's (mtDNA) isolated from rat liver and the Novikoff hepatoma grown as both solid tumors and cells in monolayer culture were examined by a variety of physicochemical techniques. Buoyant densities in analytical CsCl equilibrium gradients and thermal denaturation profiles revealed no significant differences in base composition among the mtDNA's isolated from liver, tumor, and hepatoma cells. Sedimentation in neurtral and alkaline CsCl showed no differences in mtDNA size. However, tumor and hepatoma cell mtDNA's were slightly smaller and more heterogeneous in size than liver mtDNA when molecular contour lengths were measured in the electron microscope. Based on chemical determinations, neoplastic mitochondria contained four to five times more DNA per mitochondrion than liver. Also, electron microscopy showed the proportion of mtDNA in complex forms (catenated dimers and oligomers) to be much higher in tumor (18%) and hepatoma cells (15%) than liver (4%)."} {"id": "PMID:163699", "title": "The presence of histone H1degree in human tissues.", "content": "Histone Hidegree was found to be present in a number of human tissues. It constituted 50% of the total 5% perchloric acid-soluble histone in human breast, 35%in thyroid, 12 to 18% in adrenal, and 7% in parathyroid tissues. The quantities of histone Hldegree in these human tissues were large compared with the amounts found in rat liver (8%), calf thymus (0%), and HeLa cells (0%). Although the quantity of histone Hldegree was found to vary from one type of tissue to another, it was essentially constant in normal, hyperplastic, and neoplastic human thyroid tissues.", "contents": "The presence of histone H1degree in human tissues. Histone Hidegree was found to be present in a number of human tissues. It constituted 50% of the total 5% perchloric acid-soluble histone in human breast, 35%in thyroid, 12 to 18% in adrenal, and 7% in parathyroid tissues. The quantities of histone Hldegree in these human tissues were large compared with the amounts found in rat liver (8%), calf thymus (0%), and HeLa cells (0%). Although the quantity of histone Hldegree was found to vary from one type of tissue to another, it was essentially constant in normal, hyperplastic, and neoplastic human thyroid tissues."} {"id": "PMID:163700", "title": "Prolactin and estrogen binding in transplantable hormone-dependent and autonomous rat mammary carcinoma.", "content": "A hormone-dependent subline of the transplantable rat mammary tumor MTW9 contains binding sites for both prolactin and estrogen. Prolactin binding is saturable (K-d similar to 2 times 10-9 M), hormone specific, and destroyed by proteases. By contrast, an autonomous subline derived from the same parent tumor has lost more than 75% of both prolactin- and estrogen-binding sites, although binding affinities for both hormones are unchanged. This reduction in binding sites for both prolactin and estrogen in the autonomous line may result in an incomplete recognition of the tumor cells as a target for the circulating hormones with a subsequent loss of hormone-dependent growth characteristics.", "contents": "Prolactin and estrogen binding in transplantable hormone-dependent and autonomous rat mammary carcinoma. A hormone-dependent subline of the transplantable rat mammary tumor MTW9 contains binding sites for both prolactin and estrogen. Prolactin binding is saturable (K-d similar to 2 times 10-9 M), hormone specific, and destroyed by proteases. By contrast, an autonomous subline derived from the same parent tumor has lost more than 75% of both prolactin- and estrogen-binding sites, although binding affinities for both hormones are unchanged. This reduction in binding sites for both prolactin and estrogen in the autonomous line may result in an incomplete recognition of the tumor cells as a target for the circulating hormones with a subsequent loss of hormone-dependent growth characteristics."} {"id": "PMID:163702", "title": "Messenger RNA species synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus.", "content": "The virion-associated RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV) synthesizes in vitro two size classes of RNA products similar to those observed in VSV-infected cells. One RNA product sediments at 31S with an approximate molecular weight of 2.1 X 106. The smaller products consist of at least three classes of RNA sedimenting at 17S, 14.5S, and 12S with molecular weights of 0.7 X 106, 0.52 X 106, and 0.37 X 106, respectively. Hybridization experiments show that both the 31S and 12-18S RNA products are complementary to the genome RNA, and that each class is transcribed from different nucleotide sequences. From the molecular weights of the RNA species and the hybridization experiments, it seems that almost the entire VSV genome RNA is transcribed in vitro.", "contents": "Messenger RNA species synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus. The virion-associated RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV) synthesizes in vitro two size classes of RNA products similar to those observed in VSV-infected cells. One RNA product sediments at 31S with an approximate molecular weight of 2.1 X 106. The smaller products consist of at least three classes of RNA sedimenting at 17S, 14.5S, and 12S with molecular weights of 0.7 X 106, 0.52 X 106, and 0.37 X 106, respectively. Hybridization experiments show that both the 31S and 12-18S RNA products are complementary to the genome RNA, and that each class is transcribed from different nucleotide sequences. From the molecular weights of the RNA species and the hybridization experiments, it seems that almost the entire VSV genome RNA is transcribed in vitro."} {"id": "PMID:163708", "title": "Anesthesia and the golgi apparatus: enzyme activity changes in a golgi-rich fraction of rat liver after a short ether anesthesia.", "content": "Activity changes of enzymes in isolated rat liver Golgi preparations at different times (1-48 h) after a short ether anesthesia are reported. Activity of galactosyl-transferase showed a slight gradual increase but thiamine pyrophosphatase decreased sharply, and after 24 h increased to above control level. Arylsulphatase-A remained largely unchanged, and B was significantly decreased. Acid phosphatase activity did remain at the control level, but alkali phosphatase showed a gradual and highly significant increase. Five other enzymes representing probable contaminations from other subcellular organelles, have also been assayed. Correlation is sought between the enzyme activity changes and some other metabolic effects of anesthesia.", "contents": "Anesthesia and the golgi apparatus: enzyme activity changes in a golgi-rich fraction of rat liver after a short ether anesthesia. Activity changes of enzymes in isolated rat liver Golgi preparations at different times (1-48 h) after a short ether anesthesia are reported. Activity of galactosyl-transferase showed a slight gradual increase but thiamine pyrophosphatase decreased sharply, and after 24 h increased to above control level. Arylsulphatase-A remained largely unchanged, and B was significantly decreased. Acid phosphatase activity did remain at the control level, but alkali phosphatase showed a gradual and highly significant increase. Five other enzymes representing probable contaminations from other subcellular organelles, have also been assayed. Correlation is sought between the enzyme activity changes and some other metabolic effects of anesthesia."} {"id": "PMID:163709", "title": "Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells.", "content": "Smooth muscle cells were grown from thoracic aortas of 1-year-old monkeys (Macaca nemistrina). The effect of insulin on the proliferation of these cells was studied by comparing the growth of cells in culture medium to which insulin had been added with that of cells in basal (1% monkey serum) medium and in growth-promoting 5% monkey serum. Insulin in concentrations of 10, 100, 1,000, and 10,000 muunits/ml resulted in successively greater stimulation of growth which was highly significant (P smaller than 0.001) by analysis of variance. There was a significant linear relationship between the logarithm of the insulin dose and cell growth. However, the highest concentration of insulin produced only 50% of the effect of 5% monkey serum. Serum from which insulin had been removed stimulated growth less well (P smaller than 0.05) than did untreated serum at the same concentration (5%) but had significant (P smaller than 0.05) stimulating properties compared with whole serum at a lower concentration. Cells that were older in culture life (eight or nine passages) did not show a growth response to insulin and had an attenuated response to 5% serum. The effect of insulin (100 muunits/ml) was inhibited by dibutyryl cyclic adenosine monophosphate (db-cAMP) (5 times 10-5 M), although there was a latent period of 3 days before inhibition occurred; db-cAMP had no effect on cell counts in the absence of insulin. The electron microscopic appearance of the cells was unaltered by insulin.", "contents": "Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. Smooth muscle cells were grown from thoracic aortas of 1-year-old monkeys (Macaca nemistrina). The effect of insulin on the proliferation of these cells was studied by comparing the growth of cells in culture medium to which insulin had been added with that of cells in basal (1% monkey serum) medium and in growth-promoting 5% monkey serum. Insulin in concentrations of 10, 100, 1,000, and 10,000 muunits/ml resulted in successively greater stimulation of growth which was highly significant (P smaller than 0.001) by analysis of variance. There was a significant linear relationship between the logarithm of the insulin dose and cell growth. However, the highest concentration of insulin produced only 50% of the effect of 5% monkey serum. Serum from which insulin had been removed stimulated growth less well (P smaller than 0.05) than did untreated serum at the same concentration (5%) but had significant (P smaller than 0.05) stimulating properties compared with whole serum at a lower concentration. Cells that were older in culture life (eight or nine passages) did not show a growth response to insulin and had an attenuated response to 5% serum. The effect of insulin (100 muunits/ml) was inhibited by dibutyryl cyclic adenosine monophosphate (db-cAMP) (5 times 10-5 M), although there was a latent period of 3 days before inhibition occurred; db-cAMP had no effect on cell counts in the absence of insulin. The electron microscopic appearance of the cells was unaltered by insulin."} {"id": "PMID:163710", "title": "In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.", "content": "Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis.", "contents": "In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts. Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis."} {"id": "PMID:163713", "title": "Vitiligo and dysgammaglobulinemia. A case report and family study.", "content": "This report concerns an 8 year old female with vitiligo and dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal IgM. The t-cell immune system was intact but other family members had low levels or absence of IgA. The possible relationship of dysgammaglobulinemia and vitiligo is discussed along with the classification and inheritance of the immune cell defects.", "contents": "Vitiligo and dysgammaglobulinemia. A case report and family study. This report concerns an 8 year old female with vitiligo and dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal IgM. The t-cell immune system was intact but other family members had low levels or absence of IgA. The possible relationship of dysgammaglobulinemia and vitiligo is discussed along with the classification and inheritance of the immune cell defects."} {"id": "PMID:163718", "title": "Control of phosphorylative activity in human liver mitochondria through changes in respiratory enzyme contents.", "content": "1. Oxidative phosphorylation and respiratory enzyme activities were measured in the mitochondria from the non-involved lobe of the liver in eighteen patients with massive tumour mainly localized to one lobe and from the regenerating livers of partially hepatectomized rats treated with chloramphenicol. 2. In patients, the concentrations of cytochrome a(t) varied from 40 to 170 pmol/mg of protein. In mitochondria with cytochrome a(t) concentrations more than 70 pmol/mg of protein, the phosphorylative activity per mg of mitochondrial protein was considerably higher than in controls. The mitochondrial oxidative and phosphorylative activities per unit of cytochrome a(t) were negatively correlated with the concentration of cytochrome a(t). These patients with mitochondrial cytochrome a(t) exceeding 70 pmol/mg of protein tolerated partial hepatectomy well. On the other hand, in patients with mitochondrial cytochrome a(t) less than 60 pmol/mg of protein, phosphorylative activity was very low and there was a high surgical mortality. 3. In the regenerating liver of rats treated with chloramphenicol, the oxidative and phosphorylative activities per unit of cytochrome a(t) were negatively correlated with the concentration of cytochrome a(t). 4. It is suggested that an increase in ATP-synthesizing activity per unit of respiratory assemblies is the most basic homeostatic mechanism maintaining energy production in response to an increased metabolic load upon hepatic cells.", "contents": "Control of phosphorylative activity in human liver mitochondria through changes in respiratory enzyme contents. 1. Oxidative phosphorylation and respiratory enzyme activities were measured in the mitochondria from the non-involved lobe of the liver in eighteen patients with massive tumour mainly localized to one lobe and from the regenerating livers of partially hepatectomized rats treated with chloramphenicol. 2. In patients, the concentrations of cytochrome a(t) varied from 40 to 170 pmol/mg of protein. In mitochondria with cytochrome a(t) concentrations more than 70 pmol/mg of protein, the phosphorylative activity per mg of mitochondrial protein was considerably higher than in controls. The mitochondrial oxidative and phosphorylative activities per unit of cytochrome a(t) were negatively correlated with the concentration of cytochrome a(t). These patients with mitochondrial cytochrome a(t) exceeding 70 pmol/mg of protein tolerated partial hepatectomy well. On the other hand, in patients with mitochondrial cytochrome a(t) less than 60 pmol/mg of protein, phosphorylative activity was very low and there was a high surgical mortality. 3. In the regenerating liver of rats treated with chloramphenicol, the oxidative and phosphorylative activities per unit of cytochrome a(t) were negatively correlated with the concentration of cytochrome a(t). 4. It is suggested that an increase in ATP-synthesizing activity per unit of respiratory assemblies is the most basic homeostatic mechanism maintaining energy production in response to an increased metabolic load upon hepatic cells."} {"id": "PMID:163719", "title": "The effect of 1,25-dihydroxycholecalciferol on renal tubular reabsorption of phosphate, intestinal absorption of calcium and bone histology in hypophosphataemic renal tubular rickets.", "content": "1. 1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) was given at a dose of 5-0 nmol (2-1 mug) daily by mouth for 4-12 days to three patients with hypophosphataemic (type I), vitamin D-resistant rickets. 2. 1,25-(OH)2-D3 increased intestinal absorption and urinary excretion of calcium without significant effect on the renal handling of phosphate or its plasma concentration. 3. It is concluded that in this type of vitamin D-resistant rickets the renal phosphate abnormality is unlikely to be due to diminished endogenous production of 1,25-(OH)2-D3. 4. The difference between this condition and other hypophosphataemic states is discussed.", "contents": "The effect of 1,25-dihydroxycholecalciferol on renal tubular reabsorption of phosphate, intestinal absorption of calcium and bone histology in hypophosphataemic renal tubular rickets. 1. 1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) was given at a dose of 5-0 nmol (2-1 mug) daily by mouth for 4-12 days to three patients with hypophosphataemic (type I), vitamin D-resistant rickets. 2. 1,25-(OH)2-D3 increased intestinal absorption and urinary excretion of calcium without significant effect on the renal handling of phosphate or its plasma concentration. 3. It is concluded that in this type of vitamin D-resistant rickets the renal phosphate abnormality is unlikely to be due to diminished endogenous production of 1,25-(OH)2-D3. 4. The difference between this condition and other hypophosphataemic states is discussed."} {"id": "PMID:163720", "title": "Feedback regulation of 25-hydroxycholecalciferol metabolism by vitamin D3.", "content": "1. In vitamin D-deficient chicks both vitamin D3 and 1alpha-hydroxycholecalciferol markedly decrease renal 1-hydroxylase activity and induce 24-hydroxylase activity. 2. Actinomycin D abolishes both effects. 3. These results are consistent with feedback regulation of vitamin D3 metabolism by a direct nuclear action of the vitamin or its metabolites on the kidney cells.", "contents": "Feedback regulation of 25-hydroxycholecalciferol metabolism by vitamin D3. 1. In vitamin D-deficient chicks both vitamin D3 and 1alpha-hydroxycholecalciferol markedly decrease renal 1-hydroxylase activity and induce 24-hydroxylase activity. 2. Actinomycin D abolishes both effects. 3. These results are consistent with feedback regulation of vitamin D3 metabolism by a direct nuclear action of the vitamin or its metabolites on the kidney cells."} {"id": "PMID:163721", "title": "Effect of long-acting thyroid stimulator on serum concentration of luteinizing hormone in the rat.", "content": "1. The effect of long-acting thyroid stimulator (LATS) on the serum luteinizing hormone (LH) levels of the rat in pro-oestrus has been studied. 2. The injection of three out of four LATS-containing immunoglobulin G fractions caused an increase in amounts of serum LH. 3. Adrenalectomy and dexamethason suppression did not alter this response. 4. Injection of large doses of adrenocorticotrophic hormone did not produce any increase in serum concentrations of LH. 5. It is postulated that LATS may have a direct effect on the release of LH from the pituitary gland.", "contents": "Effect of long-acting thyroid stimulator on serum concentration of luteinizing hormone in the rat. 1. The effect of long-acting thyroid stimulator (LATS) on the serum luteinizing hormone (LH) levels of the rat in pro-oestrus has been studied. 2. The injection of three out of four LATS-containing immunoglobulin G fractions caused an increase in amounts of serum LH. 3. Adrenalectomy and dexamethason suppression did not alter this response. 4. Injection of large doses of adrenocorticotrophic hormone did not produce any increase in serum concentrations of LH. 5. It is postulated that LATS may have a direct effect on the release of LH from the pituitary gland."} {"id": "PMID:163723", "title": "Disorders of movement: a mercifully short primer.", "content": "The best known biochemical pathway in the brain is probably the nigrostriatal system. Even so, its relationship to Parkinsonism is incompletely understood. Its relationship to Huntington's chorea and the dyskinetic responses is even less well understood. The significance of this system in other related disorders such as Heterogeneous system degeneration, progressive supranuclear palsy, and striatonigral degeneration is still more speculative. In an effort to elucidate underlying neuropharmacology, trials with levodopa, amantadine, haloperidol, and lithium have been undertaken. This increasing concentration in biochemical mediators reflects changing patterns in neurology where new emphasis on biochemical pathways is replacing in current interest the emphasis previously placed on more traditional neuro-anatomical pathways such as the classical ascending sensory and descending motor tracts.", "contents": "Disorders of movement: a mercifully short primer. The best known biochemical pathway in the brain is probably the nigrostriatal system. Even so, its relationship to Parkinsonism is incompletely understood. Its relationship to Huntington's chorea and the dyskinetic responses is even less well understood. The significance of this system in other related disorders such as Heterogeneous system degeneration, progressive supranuclear palsy, and striatonigral degeneration is still more speculative. In an effort to elucidate underlying neuropharmacology, trials with levodopa, amantadine, haloperidol, and lithium have been undertaken. This increasing concentration in biochemical mediators reflects changing patterns in neurology where new emphasis on biochemical pathways is replacing in current interest the emphasis previously placed on more traditional neuro-anatomical pathways such as the classical ascending sensory and descending motor tracts."} {"id": "PMID:163724", "title": "[Use of the macrophage-electrophoretic-mobility test in the diagnosis of tumours of the central nervous system (author's transl)].", "content": "The macrophage-electrophoretic-mobility (MEM) tests of Field and Caspary demonstrates the macrophage-slowing factor (MSF) produced by specifically sentised blood lymphocytes after incubation with the homologous antigen. Besides other diseases with a cellular immune reaction like multiple sclerosis malignant tumours show a reduction of the macrophage mobility in the cell electrophoresis. A significant inhibition in the MEM- test was found in 30 out of 33 tumours of the CNS. Glioblastomas, astrocytomas, spongioblastomas, ependymomas, neurinomas, meningiomas, and a myxofibroma showed a positive result (more than 10% inhibition). The results in ectodermal tumours (pituitary adenoma, craniopharyngioma) differed; secondary brain tumours showed the greatest inhibition.", "contents": "[Use of the macrophage-electrophoretic-mobility test in the diagnosis of tumours of the central nervous system (author's transl)]. The macrophage-electrophoretic-mobility (MEM) tests of Field and Caspary demonstrates the macrophage-slowing factor (MSF) produced by specifically sentised blood lymphocytes after incubation with the homologous antigen. Besides other diseases with a cellular immune reaction like multiple sclerosis malignant tumours show a reduction of the macrophage mobility in the cell electrophoresis. A significant inhibition in the MEM- test was found in 30 out of 33 tumours of the CNS. Glioblastomas, astrocytomas, spongioblastomas, ependymomas, neurinomas, meningiomas, and a myxofibroma showed a positive result (more than 10% inhibition). The results in ectodermal tumours (pituitary adenoma, craniopharyngioma) differed; secondary brain tumours showed the greatest inhibition."} {"id": "PMID:163727", "title": "[The vaso-active intestinal polypeptide in Verner-Morrison syndrome].", "content": "A 40-year-old man with the Verner-Morrison syndrome (refractory watery diarrhoea and hypokalaemia in islet-cell tumour of the pancreas) had an islet-cell carcinoma of the non-B-cell type with metastases to liver and mesenteric lymph nodes. High concentrations of a vasoactive intestinal polypeptide (VIP) were demonstrated in tumour tissue and plasma by radioimmunological tests. After surgical removal of the tumour the plasma VIP concentration fell to normal. Immunohistochemical tests of the tumour for gastrointestinal hormones demonstrated marked fluorescence only for vaso-active intestinal polypeptide. It is assumed that this polypeptide is largely responsible for the clinical signs. In the described case the severe watery diarrhoea ceased after glucocorticoid administration.", "contents": "[The vaso-active intestinal polypeptide in Verner-Morrison syndrome]. A 40-year-old man with the Verner-Morrison syndrome (refractory watery diarrhoea and hypokalaemia in islet-cell tumour of the pancreas) had an islet-cell carcinoma of the non-B-cell type with metastases to liver and mesenteric lymph nodes. High concentrations of a vasoactive intestinal polypeptide (VIP) were demonstrated in tumour tissue and plasma by radioimmunological tests. After surgical removal of the tumour the plasma VIP concentration fell to normal. Immunohistochemical tests of the tumour for gastrointestinal hormones demonstrated marked fluorescence only for vaso-active intestinal polypeptide. It is assumed that this polypeptide is largely responsible for the clinical signs. In the described case the severe watery diarrhoea ceased after glucocorticoid administration."} {"id": "PMID:163728", "title": "Differences in corticosterone and dexamethasone binding to rat brain and pituitary.", "content": "In an attempt to relate binding of 3H-corticosterone and 3H-dexamethasone to their respective potencies in blocking pituitary-adrenal activity, cytosol binding in vitro and cell nuclear binding both in vivo and in tissue slices in vitro were studied in hippocampus, hypothalamus, and anterior pituitary of adrenalectomized rats. It was found that the extremely potent glucocorticoid dexamethasone has a different pattern of binding than corticosterone in the brain and in the anterior pituitary. 1) In cytosol, differences in the estimated binding capacities in a particular tissue for 3H-corticosterone and 3H-dexamethasone and different rates of inactivation in the ability to bind the two steroids are observed. 2) For 3H-corticosterone, cytosol binding in hippocampus is higher than that in hypothalamus, and cell nuclear binding follows the same pattern. For 3H-dexamethasone, cytosol binding is again higher in the hippocampus than in hypothalamus but cell nuclear binding in the two structures is not significantly different. With respect to the anterior pituitary, binding to cell nuclei is higher for 3H-dexamethasone, while the binding to cytosol macromolecules is higher for 3H-corticosterone. 3) In vivo and in vitro cell nuclear binding for both steroids showed the same pattern among the three tissues, but in vivo data showed more distinctly the preference of 3H-dexamethasone for the anterior pituitary and the preference of 3H-corticosterone for the hippocampus. 4) When labeled in tissue slices, cell nuclear radioactivity appears to be bound to macromolecules. 5) Steroid metabolism does not occur in slices during 60 min in vitro at 25 C and cannot account for the observed tissue differences in binding. The existence of more than one population of corticosteroid-binding sites in brain and in anterior pituitary is suggested. The results are consistent with the view that the dexamethasone blockade of stress-induced ACTH release is mediated by the anterior pituitary, while the high specificity of cotricosterone binding in the hippocampus implies a specific but as yet undetermined effect of the hormone in this brain area, an effect which may not be directly related to regulation of ACTH secretion.", "contents": "Differences in corticosterone and dexamethasone binding to rat brain and pituitary. In an attempt to relate binding of 3H-corticosterone and 3H-dexamethasone to their respective potencies in blocking pituitary-adrenal activity, cytosol binding in vitro and cell nuclear binding both in vivo and in tissue slices in vitro were studied in hippocampus, hypothalamus, and anterior pituitary of adrenalectomized rats. It was found that the extremely potent glucocorticoid dexamethasone has a different pattern of binding than corticosterone in the brain and in the anterior pituitary. 1) In cytosol, differences in the estimated binding capacities in a particular tissue for 3H-corticosterone and 3H-dexamethasone and different rates of inactivation in the ability to bind the two steroids are observed. 2) For 3H-corticosterone, cytosol binding in hippocampus is higher than that in hypothalamus, and cell nuclear binding follows the same pattern. For 3H-dexamethasone, cytosol binding is again higher in the hippocampus than in hypothalamus but cell nuclear binding in the two structures is not significantly different. With respect to the anterior pituitary, binding to cell nuclei is higher for 3H-dexamethasone, while the binding to cytosol macromolecules is higher for 3H-corticosterone. 3) In vivo and in vitro cell nuclear binding for both steroids showed the same pattern among the three tissues, but in vivo data showed more distinctly the preference of 3H-dexamethasone for the anterior pituitary and the preference of 3H-corticosterone for the hippocampus. 4) When labeled in tissue slices, cell nuclear radioactivity appears to be bound to macromolecules. 5) Steroid metabolism does not occur in slices during 60 min in vitro at 25 C and cannot account for the observed tissue differences in binding. The existence of more than one population of corticosteroid-binding sites in brain and in anterior pituitary is suggested. The results are consistent with the view that the dexamethasone blockade of stress-induced ACTH release is mediated by the anterior pituitary, while the high specificity of cotricosterone binding in the hippocampus implies a specific but as yet undetermined effect of the hormone in this brain area, an effect which may not be directly related to regulation of ACTH secretion."} {"id": "PMID:163729", "title": "Rat sertoli cells: a rapid method for obtaining viable cells.", "content": "A method is described for obtaining populations of viable Sertoli cells from rat testes. Minced whole testes from rats of 15 to 29 days of age are sequentially treated with collagenase and pancreatin. The resulting suspension of cells is sedimented through a sucrose density gradient. Preparations are produced consisting of from 60% to 82% Sertoli cells, an enrichment of 2 to 5 times the proportion of Sertoli cells in whole testes of these ages. The preparations are free of interstitial cells, are essentially free of peritubular cells and contain reduced numbers of germinal cells; the main contaminating cell types are spermatogonia and spermatocytes. The Sertoli cells are considered to be 95% viable by their ability to exclude trypan blue and by subsequent culturing in vitro. The entire procedure requires 3 h. Maintenance of the Sertoli-enriched fraction in modified Eagle's minimal essential medium temporarily at 41 C allows preparations of Sertoli cell monolayer cultures consisting of 95%-98% Sertoli cells within 3 days.", "contents": "Rat sertoli cells: a rapid method for obtaining viable cells. A method is described for obtaining populations of viable Sertoli cells from rat testes. Minced whole testes from rats of 15 to 29 days of age are sequentially treated with collagenase and pancreatin. The resulting suspension of cells is sedimented through a sucrose density gradient. Preparations are produced consisting of from 60% to 82% Sertoli cells, an enrichment of 2 to 5 times the proportion of Sertoli cells in whole testes of these ages. The preparations are free of interstitial cells, are essentially free of peritubular cells and contain reduced numbers of germinal cells; the main contaminating cell types are spermatogonia and spermatocytes. The Sertoli cells are considered to be 95% viable by their ability to exclude trypan blue and by subsequent culturing in vitro. The entire procedure requires 3 h. Maintenance of the Sertoli-enriched fraction in modified Eagle's minimal essential medium temporarily at 41 C allows preparations of Sertoli cell monolayer cultures consisting of 95%-98% Sertoli cells within 3 days."} {"id": "PMID:163730", "title": "A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins.", "content": "A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed \"leukocytic endogenous mediator\" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model amino acids in the liver of normal rats. The LEM-stimulated uptake of amino acids by liver was observed in adrenalectomized, hypophysectomized, thyroidectomized, or diabetic rats and could not be duplicated by pharmacological doses of a large variety of hormones. In addition, LEM stimulated an increased uptake of alpha-aminoisobutyric acid by isolated livers during their perfusion in vitro. LEM also stimulated an increased incorporation of orotic acid into hepatic RNA of intact rats, especially into the bound ribosomal fraction. This increased synthesis of RNA preceded an enhanced hepatic production of a number of the acute-phase plasma globulins. LEM did not stimulate the adenylate cyclase-cAMP system in liver and was not found to utilize this system as a second messenger. Thus, the effects of LEM in stimulating hepatic amino acid transport appear to be direct, without mediation by other hormones, and to be independent of cAMP. On the other hand, the ability of LEM to stimulate RNA and acute phase globulin synthesis in liver may require the presence of physiological quantities of hormones such as adrenal corticoids.", "contents": "A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins. A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed \"leukocytic endogenous mediator\" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model amino acids in the liver of normal rats. The LEM-stimulated uptake of amino acids by liver was observed in adrenalectomized, hypophysectomized, thyroidectomized, or diabetic rats and could not be duplicated by pharmacological doses of a large variety of hormones. In addition, LEM stimulated an increased uptake of alpha-aminoisobutyric acid by isolated livers during their perfusion in vitro. LEM also stimulated an increased incorporation of orotic acid into hepatic RNA of intact rats, especially into the bound ribosomal fraction. This increased synthesis of RNA preceded an enhanced hepatic production of a number of the acute-phase plasma globulins. LEM did not stimulate the adenylate cyclase-cAMP system in liver and was not found to utilize this system as a second messenger. Thus, the effects of LEM in stimulating hepatic amino acid transport appear to be direct, without mediation by other hormones, and to be independent of cAMP. On the other hand, the ability of LEM to stimulate RNA and acute phase globulin synthesis in liver may require the presence of physiological quantities of hormones such as adrenal corticoids."} {"id": "PMID:163731", "title": "Adenine nucleotides in the secretory granule fraction of rat islets.", "content": "Concomitant with glucose-induced insulin release, there occurred an increase of ATP from 4.40 plus or minus 0.21 to 23.16 plus or minus 0.52 pmol/100 islets/min (P less than 0.001) in the effluent from perifused rat islets. There is a linear relationship between circulating ATP and insulin levels both in the stimulated and basal state (r = 0.689, P less than 0.01). Islets incubated with labeled adenine for a short period of time (37.5 min) showed no release of radioactivity upon subsequent glucose-induced insulin release. Islets incubated for a prolonged interval with labeled adenine (150 min) showed an increase in acid soluble radioactivity in the effluent during glucose-induced insulin release. Following incubation of the islets with labeled adenine for 150 min, approximately 5% of the homogenate radioactivity was found in the secretory granules. Using column chromatography to separate the adenine nucleotides, the distribution of radioactivity among the various nucleotides in the secretory granule fraction was found to be: AMP 54.42 plus or minus 4.96%, ADP 14.20 plus or minus 1.63%, ATP 15.39 plus or minus 3.84%, and cAMP 16.07 plus or minus 2.11%. The distribution of radioactivity in the effluent adenine nucleotides after glucose-induced insulin release was: AMP 32.83 plus or minus 4.62%, ADP 24.52 plus or minus 2.77%, ATP 28.13 plus or minus 5.45%, and cAMP 26.01 plus or minus 3.34%. The absolute levels of adenine nucleotides in the secretory granules were ATP 4.19 plus or minus 0.88, ATP madp 7.94 plus or minus 2.20 and cAMP 4.46 plus or minus 1.74 pmol/ug prot. The levels in the islet effluent were ATP, 15.30 plus or minus 2.70, ATP qDP, 29.43 plus or minus 3.49 and cAMP 7.66 plus or minus 1.93 pmol/100 islets/min for the first ten min of glucose-stimulated insulin release. Thereafter there was a rapid decline in effluent cAMP while ATP and ADP remained in essentially equivalent amounts. The distribution of radioactivity and absolute levels of the adenine nucleotides in the effluent reflects that found in the secretory granules, confirming previous observations that insulin release is occurring by exocytosis.", "contents": "Adenine nucleotides in the secretory granule fraction of rat islets. Concomitant with glucose-induced insulin release, there occurred an increase of ATP from 4.40 plus or minus 0.21 to 23.16 plus or minus 0.52 pmol/100 islets/min (P less than 0.001) in the effluent from perifused rat islets. There is a linear relationship between circulating ATP and insulin levels both in the stimulated and basal state (r = 0.689, P less than 0.01). Islets incubated with labeled adenine for a short period of time (37.5 min) showed no release of radioactivity upon subsequent glucose-induced insulin release. Islets incubated for a prolonged interval with labeled adenine (150 min) showed an increase in acid soluble radioactivity in the effluent during glucose-induced insulin release. Following incubation of the islets with labeled adenine for 150 min, approximately 5% of the homogenate radioactivity was found in the secretory granules. Using column chromatography to separate the adenine nucleotides, the distribution of radioactivity among the various nucleotides in the secretory granule fraction was found to be: AMP 54.42 plus or minus 4.96%, ADP 14.20 plus or minus 1.63%, ATP 15.39 plus or minus 3.84%, and cAMP 16.07 plus or minus 2.11%. The distribution of radioactivity in the effluent adenine nucleotides after glucose-induced insulin release was: AMP 32.83 plus or minus 4.62%, ADP 24.52 plus or minus 2.77%, ATP 28.13 plus or minus 5.45%, and cAMP 26.01 plus or minus 3.34%. The absolute levels of adenine nucleotides in the secretory granules were ATP 4.19 plus or minus 0.88, ATP madp 7.94 plus or minus 2.20 and cAMP 4.46 plus or minus 1.74 pmol/ug prot. The levels in the islet effluent were ATP, 15.30 plus or minus 2.70, ATP qDP, 29.43 plus or minus 3.49 and cAMP 7.66 plus or minus 1.93 pmol/100 islets/min for the first ten min of glucose-stimulated insulin release. Thereafter there was a rapid decline in effluent cAMP while ATP and ADP remained in essentially equivalent amounts. The distribution of radioactivity and absolute levels of the adenine nucleotides in the effluent reflects that found in the secretory granules, confirming previous observations that insulin release is occurring by exocytosis."} {"id": "PMID:163732", "title": "Genetic studies on the mechanism of action of aldosterone in mice.", "content": "Aldosterone reduced the urinary sodium:creatinine ratio and increased the potassium:creatinine ratio in a CBA strain of mice. In the Peru strain, under the same conditions, aldosterone had no detectable effect on the sodium:creatinine ratio but had an even more marked effect on the potassium:creatinine ratio. Thus, the effect of aldosterone on potassium excretion is separable from and is not simply a secondary consequence of the effect on sodium retention. Specific binding of 3H-aldosterone to kidney was reduced in Peru mice compared to CBA. However the correlation between 3H-aldosterone binding and physiological effect of the hormone on sodium excretion disappeared totally in a second generation cross between the strains. A possible explanation is that the nuclear binding of 3H-aldosterone as measured here was heterogeneous. In this same second generation cross, the ratio of bound nuclear 3H-aldosterone extracted by low-ionic strength Tris, to the residue of nuclear 3H-aldosterone resistant to extraction by 0.4M KCl, was strongly correlated to the ratio of the effect of aldosterone on potassium excretion to that on sodium excretion. Thus in these experiments the type of nuclear binding was correlated to the type of physiological effect. These results imply that the specific binding of aldosterone to renal tissue was, in some way at least, related to the mechanism of action of the hormone; and that the heterogeneity of this binding had functional significance in terms of the separable effects of aldosterone on renal sodium retention and potassium excretion in these two strains of mice.", "contents": "Genetic studies on the mechanism of action of aldosterone in mice. Aldosterone reduced the urinary sodium:creatinine ratio and increased the potassium:creatinine ratio in a CBA strain of mice. In the Peru strain, under the same conditions, aldosterone had no detectable effect on the sodium:creatinine ratio but had an even more marked effect on the potassium:creatinine ratio. Thus, the effect of aldosterone on potassium excretion is separable from and is not simply a secondary consequence of the effect on sodium retention. Specific binding of 3H-aldosterone to kidney was reduced in Peru mice compared to CBA. However the correlation between 3H-aldosterone binding and physiological effect of the hormone on sodium excretion disappeared totally in a second generation cross between the strains. A possible explanation is that the nuclear binding of 3H-aldosterone as measured here was heterogeneous. In this same second generation cross, the ratio of bound nuclear 3H-aldosterone extracted by low-ionic strength Tris, to the residue of nuclear 3H-aldosterone resistant to extraction by 0.4M KCl, was strongly correlated to the ratio of the effect of aldosterone on potassium excretion to that on sodium excretion. Thus in these experiments the type of nuclear binding was correlated to the type of physiological effect. These results imply that the specific binding of aldosterone to renal tissue was, in some way at least, related to the mechanism of action of the hormone; and that the heterogeneity of this binding had functional significance in terms of the separable effects of aldosterone on renal sodium retention and potassium excretion in these two strains of mice."} {"id": "PMID:163733", "title": "Evidence that the pars intermedia and pars nervosa of the pituitary do not secrete functionally significant quantities of ACTH.", "content": "We have compared the capacity to secrete ACTH in response to stress or adrenalectomy in control rats and in those with total hypophysectomy (H), adenohypophysectomy (AH) with preservation of the intermediate and the neural lobes, neurohypophysectomy (NH) with removal of the pars nervosa and all or part of the pars intermedia with preservation of the adenohypophysis, or incomplete adenohypophysectomy (IAH) in which a portion of the adenohypophysis and all of the pars intermedia and pars nervosa were left intact. Plasma ACTH measured with an N-terminal antibody that reacts on an equimolar basis with ACTH and alpha-MSH but not with other known pituitary hormones was elevated after ether or tourniquet stress in all except the H group. Three weeks after adrenalectomy there was an elevated basal plasma ACTH and an augmented ACTH response to stress in intact and IAH but not in AH rats. When a more specific alpha11-24 ACTH antibody was used there was a high plasma ACTH after ether stress in the IAH, NH, and intact groups but not in the AH or H groups. Adrenal weight and plasma corticosterone after tourniquet or ether stress were indistinguishable in the AH and H groups and were much higher and nearly identical in the intact, NH and IAH groups. We conclude that only the adenohypophysis secretes functionally significant amounts of ACTH. Plasma ACTH detected by the N-terminal antibody in the AH group is probably related to alpha-MSH or similar peptides and is incapable of maintaining adrenal weight or stimulating corticosterone secretion.", "contents": "Evidence that the pars intermedia and pars nervosa of the pituitary do not secrete functionally significant quantities of ACTH. We have compared the capacity to secrete ACTH in response to stress or adrenalectomy in control rats and in those with total hypophysectomy (H), adenohypophysectomy (AH) with preservation of the intermediate and the neural lobes, neurohypophysectomy (NH) with removal of the pars nervosa and all or part of the pars intermedia with preservation of the adenohypophysis, or incomplete adenohypophysectomy (IAH) in which a portion of the adenohypophysis and all of the pars intermedia and pars nervosa were left intact. Plasma ACTH measured with an N-terminal antibody that reacts on an equimolar basis with ACTH and alpha-MSH but not with other known pituitary hormones was elevated after ether or tourniquet stress in all except the H group. Three weeks after adrenalectomy there was an elevated basal plasma ACTH and an augmented ACTH response to stress in intact and IAH but not in AH rats. When a more specific alpha11-24 ACTH antibody was used there was a high plasma ACTH after ether stress in the IAH, NH, and intact groups but not in the AH or H groups. Adrenal weight and plasma corticosterone after tourniquet or ether stress were indistinguishable in the AH and H groups and were much higher and nearly identical in the intact, NH and IAH groups. We conclude that only the adenohypophysis secretes functionally significant amounts of ACTH. Plasma ACTH detected by the N-terminal antibody in the AH group is probably related to alpha-MSH or similar peptides and is incapable of maintaining adrenal weight or stimulating corticosterone secretion."} {"id": "PMID:163734", "title": "The hypercalcemic effect of parathyroid hormone and skeletal cyclic AMP.", "content": "The effects of parathyroid hormone (PTH) on bone mineral mobilization are thought to involve the second messenger cyclic AMP. Intravenous administration of 10 U PTH induced rapid and marked accumulation of cyclic AMP in calvaria and plasma of thyroparathyroidectomized rats. The changes in cyclic AMP concentrations were not sustained, but returned to near-baseline values before the rise in plasma calcium concentration was manifest. Changes in the plasma levels of calcium and cyclic AMP in response to PTH infusion were demonstrated in thyroparathyroidectomized rats who were nephrectomized as well. In a series of experiments to clarify the association of cyclic AMP accumulation and calcium mobilization, it was found that small doses of PTH induced significant elevation of plasma calcium without stimulating an accumulation of cyclic AMP in calvaria, or plasma. Furthermore, in intact rats plasma calcium levels were elevated by endogenous PTH, provoked by EGTA induced hypocalcemia, without any demonstrable change of cyclic AMP metabolism in the skeletal tissue. At a higher dose of PTH, the magnitude of the integrated change of cyclic AMP metabolism in the skeletal tissue was well correlated to the amount of calcium mobilized. These observations indicate a coupling between enhanced production of cyclic AMP and calcium mobilization in the action of PTH on bone. They also suggest that either a minute change in cyclic AMP accumulation, which can not be detected due to a high basal level of this nucleotide in the tissue, or a change in metabolism of cyclic AMP in some particular cell compartment is an early event in PTH-induced calcium mobilization.", "contents": "The hypercalcemic effect of parathyroid hormone and skeletal cyclic AMP. The effects of parathyroid hormone (PTH) on bone mineral mobilization are thought to involve the second messenger cyclic AMP. Intravenous administration of 10 U PTH induced rapid and marked accumulation of cyclic AMP in calvaria and plasma of thyroparathyroidectomized rats. The changes in cyclic AMP concentrations were not sustained, but returned to near-baseline values before the rise in plasma calcium concentration was manifest. Changes in the plasma levels of calcium and cyclic AMP in response to PTH infusion were demonstrated in thyroparathyroidectomized rats who were nephrectomized as well. In a series of experiments to clarify the association of cyclic AMP accumulation and calcium mobilization, it was found that small doses of PTH induced significant elevation of plasma calcium without stimulating an accumulation of cyclic AMP in calvaria, or plasma. Furthermore, in intact rats plasma calcium levels were elevated by endogenous PTH, provoked by EGTA induced hypocalcemia, without any demonstrable change of cyclic AMP metabolism in the skeletal tissue. At a higher dose of PTH, the magnitude of the integrated change of cyclic AMP metabolism in the skeletal tissue was well correlated to the amount of calcium mobilized. These observations indicate a coupling between enhanced production of cyclic AMP and calcium mobilization in the action of PTH on bone. They also suggest that either a minute change in cyclic AMP accumulation, which can not be detected due to a high basal level of this nucleotide in the tissue, or a change in metabolism of cyclic AMP in some particular cell compartment is an early event in PTH-induced calcium mobilization."} {"id": "PMID:163735", "title": "Changes of endocrine properties of a transplantable, multihormonal, pituitary tumor (MtT-F4) after hypophysectomy of host rats.", "content": "The transplantable rat pituitary tumor MtT-F4 failed to grow in rats hypophysectomized at the time of transplantation, but did grow in thyroxine-treated hypophysectomized rats. In the latter rats, the tumor did not stimulate the adrenals to the same extent as in control rats. When the tumor did not stimulate the adrenals to the same extent as in control rats. When the tumor cells were isolated and incubated in vitro, those from hypophysectomized thyroxine-treated rats released much less ACTH into the incubation medium than the tumor cells from control rats. They also released significantly less growth hormone than tumor cells from intact, intact thyroxine-treated, and thyroidectomized thyroxine-treated rats. Prolactin release by the isolated tumor cells in vitro was the same in all groups studied. The results suggest that the hypophysectomy and thyroxine treatment of the host rat might selectively influence the production of hormones by the MtT-F4 transplantable rat pituitary tumor.", "contents": "Changes of endocrine properties of a transplantable, multihormonal, pituitary tumor (MtT-F4) after hypophysectomy of host rats. The transplantable rat pituitary tumor MtT-F4 failed to grow in rats hypophysectomized at the time of transplantation, but did grow in thyroxine-treated hypophysectomized rats. In the latter rats, the tumor did not stimulate the adrenals to the same extent as in control rats. When the tumor did not stimulate the adrenals to the same extent as in control rats. When the tumor cells were isolated and incubated in vitro, those from hypophysectomized thyroxine-treated rats released much less ACTH into the incubation medium than the tumor cells from control rats. They also released significantly less growth hormone than tumor cells from intact, intact thyroxine-treated, and thyroidectomized thyroxine-treated rats. Prolactin release by the isolated tumor cells in vitro was the same in all groups studied. The results suggest that the hypophysectomy and thyroxine treatment of the host rat might selectively influence the production of hormones by the MtT-F4 transplantable rat pituitary tumor."} {"id": "PMID:163736", "title": "Effect of lithium on catecholamine-induced antidiuresis and cyclic AMP in dog kidneys.", "content": "Patients treated with lithium salt have an inability to concentrate urine, possible due to the inhibition of the antidiuretic effect of vasopressin. Since beta adrenergic stimulation also induces antidiuresis, a possible effect of lithium on the catecholamine-induced antidiuresis was investigated in dog kidneys. The urinary concentrating ability induced by the iv injection of isoproterenol 0.1 mug/kg was markedly inhibited in the lithium-treated animals (plasma lithium 1.13 plus or minus 0.10 mM). The increase of cyclic AMP concentration by 1 muM isoproterenol was also significantly less in the renal medullary slices obtained from the lithium-treated animals than in those obtained from the control animals. These findings suggest that the inability to concentrate urine in the patients treated with lithium salt is probably due to the inhibition of the antidiuretic effect of catecholamine as well as that of vasopressin; and the inhibitory mechanism of lithium on the catecholamine-induced antidiuresis is possibly through the inhibition of the catecholamine-dependent cycle AMP system in renal medulla.", "contents": "Effect of lithium on catecholamine-induced antidiuresis and cyclic AMP in dog kidneys. Patients treated with lithium salt have an inability to concentrate urine, possible due to the inhibition of the antidiuretic effect of vasopressin. Since beta adrenergic stimulation also induces antidiuresis, a possible effect of lithium on the catecholamine-induced antidiuresis was investigated in dog kidneys. The urinary concentrating ability induced by the iv injection of isoproterenol 0.1 mug/kg was markedly inhibited in the lithium-treated animals (plasma lithium 1.13 plus or minus 0.10 mM). The increase of cyclic AMP concentration by 1 muM isoproterenol was also significantly less in the renal medullary slices obtained from the lithium-treated animals than in those obtained from the control animals. These findings suggest that the inability to concentrate urine in the patients treated with lithium salt is probably due to the inhibition of the antidiuretic effect of catecholamine as well as that of vasopressin; and the inhibitory mechanism of lithium on the catecholamine-induced antidiuresis is possibly through the inhibition of the catecholamine-dependent cycle AMP system in renal medulla."} {"id": "PMID:163737", "title": "3H-estradiol distribution in female, androgenized female, and male rats at 100 and 200 days of age.", "content": "Tissue distribution of radioactivity was studied 48 h after gonadectomy and 1 h after iv injection of 3H-estradiol (1 mug/kg body wt) in 100- and 200-day-old normal female rats, female rats androgenized with 30, 100 or 1250 mug testosterone propionate (TP) at 5 days of age, and male rats. Receptor-mediated uptake of estradiol, as shown by diethylstilbestrol (DES) competition, was highest in preoptic area-anterior hypothalamus (POA-AH) and median eminence-basal hypothalamus (ME-BH), but also occurred in dorsal hypothalamus, pre-hypothalamic area, amygdala and septum in all groups. At 100 days of age there were no differences in brain radioactivity levels between females and androgenized females or males. At 200 days of age radioactivity levels in POA-AH and ME-BH tended to be lower in androgenized female and male rats than in normal females. Also, radioactivity levels in the amygdala were lower in the 1250 mug TP-treated females than in normal females. When expressed per unit fresh weight, uptake in the anterior pituitary tended to be lower in androgenized rats at 100 days of age and was higher in males at 200 days of age than in normal females, but did not differ among any of the groups when expressed as uptake per organ. Thus, the well-known differences among these groups in neural regulation of gonadotropin secretion and sex behavior were not correlated with consistent differences in specific estradiol binding by hypothalamic or other brain areas or pituitary. The uterus took up less estradiol in androgenized females than in control females at both ages. Estradiol receptor activity was demonstrated in kidney of all animals and in seminal vesicles. At both ages radioactivity levels in the toluene and ethanol extracts of lever and kidney were strikingly higher in males than in the female groups. Reviewing the data, it appears that despite some evidence of differences between groups, males, females and androgenized females all have relatively similar limited-capacity, estradiol-uptake systems in brain and pituitary, as measured under the conditions of the present study.", "contents": "3H-estradiol distribution in female, androgenized female, and male rats at 100 and 200 days of age. Tissue distribution of radioactivity was studied 48 h after gonadectomy and 1 h after iv injection of 3H-estradiol (1 mug/kg body wt) in 100- and 200-day-old normal female rats, female rats androgenized with 30, 100 or 1250 mug testosterone propionate (TP) at 5 days of age, and male rats. Receptor-mediated uptake of estradiol, as shown by diethylstilbestrol (DES) competition, was highest in preoptic area-anterior hypothalamus (POA-AH) and median eminence-basal hypothalamus (ME-BH), but also occurred in dorsal hypothalamus, pre-hypothalamic area, amygdala and septum in all groups. At 100 days of age there were no differences in brain radioactivity levels between females and androgenized females or males. At 200 days of age radioactivity levels in POA-AH and ME-BH tended to be lower in androgenized female and male rats than in normal females. Also, radioactivity levels in the amygdala were lower in the 1250 mug TP-treated females than in normal females. When expressed per unit fresh weight, uptake in the anterior pituitary tended to be lower in androgenized rats at 100 days of age and was higher in males at 200 days of age than in normal females, but did not differ among any of the groups when expressed as uptake per organ. Thus, the well-known differences among these groups in neural regulation of gonadotropin secretion and sex behavior were not correlated with consistent differences in specific estradiol binding by hypothalamic or other brain areas or pituitary. The uterus took up less estradiol in androgenized females than in control females at both ages. Estradiol receptor activity was demonstrated in kidney of all animals and in seminal vesicles. At both ages radioactivity levels in the toluene and ethanol extracts of lever and kidney were strikingly higher in males than in the female groups. Reviewing the data, it appears that despite some evidence of differences between groups, males, females and androgenized females all have relatively similar limited-capacity, estradiol-uptake systems in brain and pituitary, as measured under the conditions of the present study."} {"id": "PMID:163738", "title": "Inhibition by iodide of the activation of the thyroid cyclic 3',5'-AMP system.", "content": "The action of iodide on the cyclic AMP system of dog thyroid slices has been studied. Iodide inhibits the enhancement of cyclic AMP accumulation in the presence of TSH. Such an effect is also observed in horse, beef and sheep thyroid slices, but not in dog kidney slices stimulated by parathyroid hormone or in rat parotid slices stimulated by isoproterenol. The effect in dog thyroid slices is suppressed by 1mM NaClO4, 1mM methimazole and 1mM propylthiouracil. Similar data have been obtained for prostaglandin E1 stimulation. Effects of thyrotropin mediated by cyclic AMP, i.e., activation of iodothyronine secretion, 1-14C-glucose oxidation, and lactate formation, were also inhibited by iodide but not by iodide and methimazole. Similar activations when caused by dbcAMP were not inhibited by iodide. The data suggest a model in which an intracellular agent resulting from the oxidation of iodide acts on the thyroid cyclic AMP system.", "contents": "Inhibition by iodide of the activation of the thyroid cyclic 3',5'-AMP system. The action of iodide on the cyclic AMP system of dog thyroid slices has been studied. Iodide inhibits the enhancement of cyclic AMP accumulation in the presence of TSH. Such an effect is also observed in horse, beef and sheep thyroid slices, but not in dog kidney slices stimulated by parathyroid hormone or in rat parotid slices stimulated by isoproterenol. The effect in dog thyroid slices is suppressed by 1mM NaClO4, 1mM methimazole and 1mM propylthiouracil. Similar data have been obtained for prostaglandin E1 stimulation. Effects of thyrotropin mediated by cyclic AMP, i.e., activation of iodothyronine secretion, 1-14C-glucose oxidation, and lactate formation, were also inhibited by iodide but not by iodide and methimazole. Similar activations when caused by dbcAMP were not inhibited by iodide. The data suggest a model in which an intracellular agent resulting from the oxidation of iodide acts on the thyroid cyclic AMP system."} {"id": "PMID:163739", "title": "A short method for the isolation of somatotrophs from the rat pituitary gland.", "content": "Application of a density gradient centrifugation procedure for the isolation of somatotrophs from dispersed rat anterior pituitary cells is described. Two sequential discontinuous gradients of bovine serum albumin are used to enrich the somatotroph population from a frequency of 38% in the initial cell suspension to a final purity of 85%. The isolated somatotrophs retain both histochemical and ultrastructural integrity throughout the isolation procedure. The isolated somatotrophs also release immunoassayable growth hormone when incubated with 6 mM dibutyryl 3',5'-cyclic AMP. The method offers the advantages of being both simple and short.", "contents": "A short method for the isolation of somatotrophs from the rat pituitary gland. Application of a density gradient centrifugation procedure for the isolation of somatotrophs from dispersed rat anterior pituitary cells is described. Two sequential discontinuous gradients of bovine serum albumin are used to enrich the somatotroph population from a frequency of 38% in the initial cell suspension to a final purity of 85%. The isolated somatotrophs retain both histochemical and ultrastructural integrity throughout the isolation procedure. The isolated somatotrophs also release immunoassayable growth hormone when incubated with 6 mM dibutyryl 3',5'-cyclic AMP. The method offers the advantages of being both simple and short."} {"id": "PMID:163740", "title": "Stimulation of the uptake of alpha-aminoisobutyric acid in rat thymocytes by L-triiodothyronine: a comparison with insulin and dibutyryl cyclic AMP.", "content": "L-Triiodothyronine in vitro increased the uptake of the non-metabolizable amino acid, alpha-aminoisobutyrate, into isolated rat thymocytes. This effect was evident at extracellular free hormone concentrations of 10-7 to 5 times 10-8M and was due to a marked inhibition of amino acid efflux. In contrast, insulin and dibutyryl cyclic AMP, which also increased uptake in these cells, acted to stimulate amino acid influx. When L-triiodothyronine was added to maximally effective concentrations of either insulin or dibutyryl cyclic AMP, the resultant effect was the sum of the effect of each hormone added individually. These studies extended previous observations which indicate that thyroid hormones stimulate the cellular uptake of amino acids, and they provide a convenient system for the study of thyroid hormone action in vitro.", "contents": "Stimulation of the uptake of alpha-aminoisobutyric acid in rat thymocytes by L-triiodothyronine: a comparison with insulin and dibutyryl cyclic AMP. L-Triiodothyronine in vitro increased the uptake of the non-metabolizable amino acid, alpha-aminoisobutyrate, into isolated rat thymocytes. This effect was evident at extracellular free hormone concentrations of 10-7 to 5 times 10-8M and was due to a marked inhibition of amino acid efflux. In contrast, insulin and dibutyryl cyclic AMP, which also increased uptake in these cells, acted to stimulate amino acid influx. When L-triiodothyronine was added to maximally effective concentrations of either insulin or dibutyryl cyclic AMP, the resultant effect was the sum of the effect of each hormone added individually. These studies extended previous observations which indicate that thyroid hormones stimulate the cellular uptake of amino acids, and they provide a convenient system for the study of thyroid hormone action in vitro."} {"id": "PMID:163741", "title": "The conformation of adenosine diphosphoribose and 8-bromoadenosine diphosphoribose when bound to liver alcohol dehydrogenase.", "content": "8-Bromo-adenosine diphosphoribose (br8 ADP-Rib) and nicotinamide 8-bromoadenine dinucleotide (Nbr8AD+) which are analogues of the coenzyme NAD+, were prepared and their liver alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in hydrogen transport and br8ADP-Rib is a coenzyme competitive inhibitor for the enzymes liver alcohol dehydrogenase and yeast alcohol dehydrogenase. X-ray data were obtained for the complex between liver alcohol dehydrogenase and br8ADP-Rib to 0.45 nm resolution and for the liver alcohol dehydrogenase-adenosine diphosphoribose complex to 0.29-nm resolution. The conformations of these analogues were determined from the X-ray data. It was found that ADP-Rib had a conformation very similar to the corresponding part of NAD+, when NAD+ is bound to lactate and malate dehydrogenase. br8ADP-Rib had the same anti conformation of the adenine ring with respect to the ribose as ADP-Rib and NAD+, in contrast to the syn conformation found in 8-bromo-adenosine. The overcrowding at the 8-position is relieved in br8ADP-Rib by having the ribose in the 2' endo condormation instead of the usual 3' endo as in ADP-Rib and NAD+.", "contents": "The conformation of adenosine diphosphoribose and 8-bromoadenosine diphosphoribose when bound to liver alcohol dehydrogenase. 8-Bromo-adenosine diphosphoribose (br8 ADP-Rib) and nicotinamide 8-bromoadenine dinucleotide (Nbr8AD+) which are analogues of the coenzyme NAD+, were prepared and their liver alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in hydrogen transport and br8ADP-Rib is a coenzyme competitive inhibitor for the enzymes liver alcohol dehydrogenase and yeast alcohol dehydrogenase. X-ray data were obtained for the complex between liver alcohol dehydrogenase and br8ADP-Rib to 0.45 nm resolution and for the liver alcohol dehydrogenase-adenosine diphosphoribose complex to 0.29-nm resolution. The conformations of these analogues were determined from the X-ray data. It was found that ADP-Rib had a conformation very similar to the corresponding part of NAD+, when NAD+ is bound to lactate and malate dehydrogenase. br8ADP-Rib had the same anti conformation of the adenine ring with respect to the ribose as ADP-Rib and NAD+, in contrast to the syn conformation found in 8-bromo-adenosine. The overcrowding at the 8-position is relieved in br8ADP-Rib by having the ribose in the 2' endo condormation instead of the usual 3' endo as in ADP-Rib and NAD+."} {"id": "PMID:163742", "title": "Effects of fasting on the control of fatty-acid synthesis in hepatoma 7777 and host liver. Role of long-chain fatty acyl-CoA,, the mitochondrial citrate transporter and pyruvate dehydrogenase activity.", "content": "The effects of fasting on the rate of fatty acid synthesis, the properties of the mitochondrial citrate transporter and on pyruvate dehydrogenase activity were investigated in \"poorly-differentiated\" tmorris hepatoma 7777 and in host liver preparations. The properties of the citrate transporter from hepatoma mitochondria were similar to those of host liver mitochondria, with the exception that the Km for the liver mitochondrial citrate transporter was 248 plus or minus 20 mu M while that in hepatoma mitochondria was less than 75 mu M. The acid-insoluble CoA content was 180 plus or minus 20 pmol/mg protein in the hepatoma and remained essentially unchanged in the fasted state, while the acid-insoluble CoA levels in livers from fed rats was 720 plus or minus 80 pmol/mg protein and were increased to 1050 plus or minus 50 pmol/mg protein during fasting. After a 36-h fast, the rate of lipogenesis and the percentage of pyruvate dehydrogenase present in the active form were each decreased by approximately 80% in host liver preparations. In contrast, the rate of lipogenesis by hepatoma slices did not decrease during fasting, and essentially all pyruvate dehydrogenase present was in the active form of hepatomas obtained from either fed or fasted animals. Implications concerning the identification of possible regulatory sites in the control of lipogenesis were discussed in relation to the above observations.", "contents": "Effects of fasting on the control of fatty-acid synthesis in hepatoma 7777 and host liver. Role of long-chain fatty acyl-CoA,, the mitochondrial citrate transporter and pyruvate dehydrogenase activity. The effects of fasting on the rate of fatty acid synthesis, the properties of the mitochondrial citrate transporter and on pyruvate dehydrogenase activity were investigated in \"poorly-differentiated\" tmorris hepatoma 7777 and in host liver preparations. The properties of the citrate transporter from hepatoma mitochondria were similar to those of host liver mitochondria, with the exception that the Km for the liver mitochondrial citrate transporter was 248 plus or minus 20 mu M while that in hepatoma mitochondria was less than 75 mu M. The acid-insoluble CoA content was 180 plus or minus 20 pmol/mg protein in the hepatoma and remained essentially unchanged in the fasted state, while the acid-insoluble CoA levels in livers from fed rats was 720 plus or minus 80 pmol/mg protein and were increased to 1050 plus or minus 50 pmol/mg protein during fasting. After a 36-h fast, the rate of lipogenesis and the percentage of pyruvate dehydrogenase present in the active form were each decreased by approximately 80% in host liver preparations. In contrast, the rate of lipogenesis by hepatoma slices did not decrease during fasting, and essentially all pyruvate dehydrogenase present was in the active form of hepatomas obtained from either fed or fasted animals. Implications concerning the identification of possible regulatory sites in the control of lipogenesis were discussed in relation to the above observations."} {"id": "PMID:163743", "title": "Thalamo-cortical projections for recruiting responses and spindling-like responses in the parietal cortex.", "content": "1. The thalamic neurones sending their axons to the parietal association cortex (middle suprasylvian gyrus) and receiving monosynaptic excitation from the cerebellar (interpositus or lateral) nucleus were recorded with microelectrodes extracellularly and intracellularly around the anterior ventral (VA) nucleus of the thalamus in cats. Such thalamic neurones are known to carry exclusively the impulses responsible for superficial thalamo-cortical (T-C) responses in the parietal cortex, being called superficial T-C neurones (see Sasaki et al., 1972a, b). 2. Repetitive (6--9/sec) stimulation of the centrum medianum-parafascicular complex (CM) or the intralaminar nuclei (IL) of the thalamus elicited grouped spike discharges of the neurone in synchronization with the recruiting responses in the parietal cortex. The grouped discharges usually preceded the respective cortical responses by several milliseconds. Numbers of the spikes in the grouped discharges increased and decreased as the recruiting responses waxed and waned on the repetitive stimulation. 3. The superficial T-C neurones also showed similar grouped discharges in synchronization with spindling-like, surface-negative cortical responses which occurred spontaneously or were evoked by single thalamic stimulation. 4. It was concluded that the superficial T-C neurons can convey impulses for recruiting responses and spindling-like responses from the thalamus directly to the cerebral cortex. They are supposed to constitute the final T-C pathway of the neuronal circuits of the recruiting system, i.e., non-specific T-C projection system.", "contents": "Thalamo-cortical projections for recruiting responses and spindling-like responses in the parietal cortex. 1. The thalamic neurones sending their axons to the parietal association cortex (middle suprasylvian gyrus) and receiving monosynaptic excitation from the cerebellar (interpositus or lateral) nucleus were recorded with microelectrodes extracellularly and intracellularly around the anterior ventral (VA) nucleus of the thalamus in cats. Such thalamic neurones are known to carry exclusively the impulses responsible for superficial thalamo-cortical (T-C) responses in the parietal cortex, being called superficial T-C neurones (see Sasaki et al., 1972a, b). 2. Repetitive (6--9/sec) stimulation of the centrum medianum-parafascicular complex (CM) or the intralaminar nuclei (IL) of the thalamus elicited grouped spike discharges of the neurone in synchronization with the recruiting responses in the parietal cortex. The grouped discharges usually preceded the respective cortical responses by several milliseconds. Numbers of the spikes in the grouped discharges increased and decreased as the recruiting responses waxed and waned on the repetitive stimulation. 3. The superficial T-C neurones also showed similar grouped discharges in synchronization with spindling-like, surface-negative cortical responses which occurred spontaneously or were evoked by single thalamic stimulation. 4. It was concluded that the superficial T-C neurons can convey impulses for recruiting responses and spindling-like responses from the thalamus directly to the cerebral cortex. They are supposed to constitute the final T-C pathway of the neuronal circuits of the recruiting system, i.e., non-specific T-C projection system."} {"id": "PMID:163770", "title": "Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development.", "content": "Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of CAMP.", "contents": "Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development. Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of CAMP."} {"id": "PMID:163771", "title": "Impaired hormonal regulation of enzyme activity during aging.", "content": "A general feature of all aging populations is the progressively impaired ability to adapt to changes in the surrounding environment. Biochemical expressions of adaptive response include modifications in the rates of enzyme synthesis and degradation, as well as alterations in physiological activity. Therefore, the effects of aging on enzyme adaptation were surveyed in an attempt to explore fundamental biochemical mechanisms in the deterioration of responsiveness. The ability to stimulate adaptive increases in the activity of a large number of enzymes is impared during aging in a variety of tissues from several different species. The impaired capability for liver enzyme adaptation in a rigorously controlled colony of aging male Sprague-Dawley rats probably reflects alterations in hormonal control mechanisms. The present article reviews and evaluates our interest in understanding the effects of aging on regulation of liver enzyme activity by the hormones, insulin and corticosterone. Specific areas currently under investigation include: (1) the regulation of their concentrations in blood; (2) the integrity of their receptor systems in liver; and (3) effectiveness of the endogenous hormone pools fromthe viewpoints fothe availability of physiological antagonists and the potential for alterations in molecular structure.", "contents": "Impaired hormonal regulation of enzyme activity during aging. A general feature of all aging populations is the progressively impaired ability to adapt to changes in the surrounding environment. Biochemical expressions of adaptive response include modifications in the rates of enzyme synthesis and degradation, as well as alterations in physiological activity. Therefore, the effects of aging on enzyme adaptation were surveyed in an attempt to explore fundamental biochemical mechanisms in the deterioration of responsiveness. The ability to stimulate adaptive increases in the activity of a large number of enzymes is impared during aging in a variety of tissues from several different species. The impaired capability for liver enzyme adaptation in a rigorously controlled colony of aging male Sprague-Dawley rats probably reflects alterations in hormonal control mechanisms. The present article reviews and evaluates our interest in understanding the effects of aging on regulation of liver enzyme activity by the hormones, insulin and corticosterone. Specific areas currently under investigation include: (1) the regulation of their concentrations in blood; (2) the integrity of their receptor systems in liver; and (3) effectiveness of the endogenous hormone pools fromthe viewpoints fothe availability of physiological antagonists and the potential for alterations in molecular structure."} {"id": "PMID:163772", "title": "Age-related changes in glucocorticoid binding by rat splenic leukocytes: possible cause of altered adaptive responsiveness.", "content": "Splenic leukocytes of senescent rats (24-26 mo) exhibit a 60% reduction in cortisol-induced inhibition of 3-H-uridine uptake when compared to mature adult animals (12-14 mo). The degree of inhibition is directly proportional to cortisol dosage up to 2 X 10-6 M. Specific binding of physiological (nanomolar) concentrations of 3-H-cortisol by leukocytic cytosol macromolecules is reduced by over 40% in the older animals. Moreover, Scatchard analyses reveal 60% fewer specific glucocorticoid binding sites in the cytosols of cells from the senescent rats. Such analyses were performed in vitro at 0 C to eliminate metabolism of steroids. In addition, 3-H-dexamethasone was used instead of 3-H-cortisol to eliminate binding to plasma (or serum) transcortin. Inhibition of 3-H-uridine uptake requires specific glucocorticoid binding. The degree of inhibition at varying glucocorticoid dosages is proportional to the amount of specific binding to cytoplasmic macromolecules. Thus, age-related reduction in specific glucocorticoid binding sites may be at least partially responsible for altered responsiveness of splenic leukocytes to these hormones.", "contents": "Age-related changes in glucocorticoid binding by rat splenic leukocytes: possible cause of altered adaptive responsiveness. Splenic leukocytes of senescent rats (24-26 mo) exhibit a 60% reduction in cortisol-induced inhibition of 3-H-uridine uptake when compared to mature adult animals (12-14 mo). The degree of inhibition is directly proportional to cortisol dosage up to 2 X 10-6 M. Specific binding of physiological (nanomolar) concentrations of 3-H-cortisol by leukocytic cytosol macromolecules is reduced by over 40% in the older animals. Moreover, Scatchard analyses reveal 60% fewer specific glucocorticoid binding sites in the cytosols of cells from the senescent rats. Such analyses were performed in vitro at 0 C to eliminate metabolism of steroids. In addition, 3-H-dexamethasone was used instead of 3-H-cortisol to eliminate binding to plasma (or serum) transcortin. Inhibition of 3-H-uridine uptake requires specific glucocorticoid binding. The degree of inhibition at varying glucocorticoid dosages is proportional to the amount of specific binding to cytoplasmic macromolecules. Thus, age-related reduction in specific glucocorticoid binding sites may be at least partially responsible for altered responsiveness of splenic leukocytes to these hormones."} {"id": "PMID:163773", "title": "Impotence in patients with chronic renal failure on dialysis: its frequency and etiology.", "content": "Fourteen patients with chronic renal failure and on a hemodialysis program underwent neurologic, psychiatric, and endocrine studies to determine the frequency and etiology of impotence in uremics. The data suggest that impotence is more frequent in the chronic dialysis group than in the general population. All seven of the impotent men were found to have prolonged nerve conduct on velocity and absent bulbocavernosus reflexes. Several of the impotent men also had clinical depression and low plasma testosterone levels. Neuropathy may be a significant factor in the pathogenesis of impotence in the uremic, but the importance of both psychiatric and endocrine influences must be strongly considered.", "contents": "Impotence in patients with chronic renal failure on dialysis: its frequency and etiology. Fourteen patients with chronic renal failure and on a hemodialysis program underwent neurologic, psychiatric, and endocrine studies to determine the frequency and etiology of impotence in uremics. The data suggest that impotence is more frequent in the chronic dialysis group than in the general population. All seven of the impotent men were found to have prolonged nerve conduct on velocity and absent bulbocavernosus reflexes. Several of the impotent men also had clinical depression and low plasma testosterone levels. Neuropathy may be a significant factor in the pathogenesis of impotence in the uremic, but the importance of both psychiatric and endocrine influences must be strongly considered."} {"id": "PMID:163776", "title": "Cell membrane changes in chronically diabetic rats.", "content": "We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell \"ghosts\" showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged. To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals. In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover.", "contents": "Cell membrane changes in chronically diabetic rats. We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell \"ghosts\" showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged. To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals. In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover."} {"id": "PMID:163778", "title": "Intravenous pentagastrin as a partial agonist of gastric secretion in man: evidence in favor of the existence of hormonal inhibitory sites.", "content": "The gastric secretory response to prompt intravenous injection of pentagastrin was investigated in 3 normal subjects and 3 patients with duodenal ulcer. The highest responses to pentagastrin and histamine were correlated. Intravenous pentagastrin in a dose of 0,5 mug per kg could thus achieve the same extent of discrimination between individuals with a 10-fold economy in dosage over subcutaneous pentagastrin. Sensitivity to pentagastrin, expressed in the D50, was higher in patients with duodenal ulcer. Unexpectedly, the highest response to intravenous pentagastrin was only 40% of the peak response to subcutaneous histamine. Accordingly, intravenous pentagastrin acted as a partial agonist with an efficacy of about 0.4. The effect of prompt injection of pentagastrin contrasted with the effect of slow intravenous infusion of pentagastrin, as well as with the effects of gastrin-17 given by either prompt injection or slow infusion. A model is proposed to account for these and related findings in other species. The secretory receptor for gastrin and its analogues is viewed as consisting of two sites: a high affinity stimulatory site and a low affinity inhibitory site. Partial agonism after prompt intravenous injection would result from blood and tissue transients which are successively too high (partially inhibitory) and low (stimulatory). The disparate effects of analogues and the differences between species would be determined by the relative affinities of the two sites. The overflow of stimulant into inhibitory sites would account for the reversal of response at high doses observed in numerous studies.", "contents": "Intravenous pentagastrin as a partial agonist of gastric secretion in man: evidence in favor of the existence of hormonal inhibitory sites. The gastric secretory response to prompt intravenous injection of pentagastrin was investigated in 3 normal subjects and 3 patients with duodenal ulcer. The highest responses to pentagastrin and histamine were correlated. Intravenous pentagastrin in a dose of 0,5 mug per kg could thus achieve the same extent of discrimination between individuals with a 10-fold economy in dosage over subcutaneous pentagastrin. Sensitivity to pentagastrin, expressed in the D50, was higher in patients with duodenal ulcer. Unexpectedly, the highest response to intravenous pentagastrin was only 40% of the peak response to subcutaneous histamine. Accordingly, intravenous pentagastrin acted as a partial agonist with an efficacy of about 0.4. The effect of prompt injection of pentagastrin contrasted with the effect of slow intravenous infusion of pentagastrin, as well as with the effects of gastrin-17 given by either prompt injection or slow infusion. A model is proposed to account for these and related findings in other species. The secretory receptor for gastrin and its analogues is viewed as consisting of two sites: a high affinity stimulatory site and a low affinity inhibitory site. Partial agonism after prompt intravenous injection would result from blood and tissue transients which are successively too high (partially inhibitory) and low (stimulatory). The disparate effects of analogues and the differences between species would be determined by the relative affinities of the two sites. The overflow of stimulant into inhibitory sites would account for the reversal of response at high doses observed in numerous studies."} {"id": "PMID:163779", "title": "In vitro interactions of gastrointestinal hormones on cyclic adenosine 3':5'-monophosphate levels and amylase output in the rat pancreas.", "content": "Four-fold increases in cyclic AMP levels were observed 5 to 10 min after rat pancreatic fragments were incubated with 10-7 M secretin or 10-6 M vasoactive intestinal polypeptide (VIP), in addition to 10 mM theophylline. From dose-response curves it appears that, on a molar basis, the potency of secretin was 20 times higher than that of VIP. It is concluded that cyclic AMP is probably the intracellular messenger of both secretin and VIP in centroacinar cells. Pancreozymin, caerulein, and the C-terminal octapeptide of pancreozymin inhibited the production of cyclic AMP observed with secretin of VIP, suggesting that the first three peptides were acting at a binding site different from the agonists, but coupled with the same adenylate cyclase. In acinar cells, secretin was able to exert slight ecbolic effects, and was also able to potentiate the effect of maximal concentrations of pancreozymin, caerulein, or the C-terminal octapeptide of pancreozymin. There was no simple correlation between amylase output and cyclic AMP levels, and copious amylase secretion was elicited even at control levels of cyclic AMP. Glucagon was neither an agonist nor an antagonist of any of the other polypeptides tested.", "contents": "In vitro interactions of gastrointestinal hormones on cyclic adenosine 3':5'-monophosphate levels and amylase output in the rat pancreas. Four-fold increases in cyclic AMP levels were observed 5 to 10 min after rat pancreatic fragments were incubated with 10-7 M secretin or 10-6 M vasoactive intestinal polypeptide (VIP), in addition to 10 mM theophylline. From dose-response curves it appears that, on a molar basis, the potency of secretin was 20 times higher than that of VIP. It is concluded that cyclic AMP is probably the intracellular messenger of both secretin and VIP in centroacinar cells. Pancreozymin, caerulein, and the C-terminal octapeptide of pancreozymin inhibited the production of cyclic AMP observed with secretin of VIP, suggesting that the first three peptides were acting at a binding site different from the agonists, but coupled with the same adenylate cyclase. In acinar cells, secretin was able to exert slight ecbolic effects, and was also able to potentiate the effect of maximal concentrations of pancreozymin, caerulein, or the C-terminal octapeptide of pancreozymin. There was no simple correlation between amylase output and cyclic AMP levels, and copious amylase secretion was elicited even at control levels of cyclic AMP. Glucagon was neither an agonist nor an antagonist of any of the other polypeptides tested."} {"id": "PMID:163780", "title": "Relationship of serum alpha-fetoprotein to the severity and duration of illness in patients with viral hepatitis.", "content": "Using a radioimmunoassay which detect concentrations of alpha-fetoprotein as low as 5 ng per ml, 38% of 176 patients with viral hepatitis compared with health volunteers and patients with chronic diseases not affecting the liver. When separated into two groups based on histological classification of liver biopsy specimens, differences in the degree and frequency of increased serum alpha-fetoprotein were related to the severity of the hepatic lesion. Of 75 patients with the lesion of viral subacute hepatic necrosis, in which zones of necrosis bridge adjacent portal triads or central veins, 52% had increased values, and 12% had levels ranging from 500 to 3300 ng per ml. In contrast, only 28% of the 101 patients without bridging necrosis had increased values, and none had levels that exceeded 500 ng per ml. In the patients with subacute hepatic necrosis, comparison of alpha-fetoprotein concentrations with the duration of illness indicated that the protein rose to peak levels in serum as the SGOT was declining. This was confirmed by serial observations in 10 patients. Thus, the increase of alpha-fetoprotein in the sera of patients with severe hepatitis occurs as liver necrosis is subsiding. Due to other known features of alpha-fetoprotein, it is intriguing to speculate that the increase in serum levels of this protein in viral hepatitis reflects hepatic regeneration after parenchymal damage.", "contents": "Relationship of serum alpha-fetoprotein to the severity and duration of illness in patients with viral hepatitis. Using a radioimmunoassay which detect concentrations of alpha-fetoprotein as low as 5 ng per ml, 38% of 176 patients with viral hepatitis compared with health volunteers and patients with chronic diseases not affecting the liver. When separated into two groups based on histological classification of liver biopsy specimens, differences in the degree and frequency of increased serum alpha-fetoprotein were related to the severity of the hepatic lesion. Of 75 patients with the lesion of viral subacute hepatic necrosis, in which zones of necrosis bridge adjacent portal triads or central veins, 52% had increased values, and 12% had levels ranging from 500 to 3300 ng per ml. In contrast, only 28% of the 101 patients without bridging necrosis had increased values, and none had levels that exceeded 500 ng per ml. In the patients with subacute hepatic necrosis, comparison of alpha-fetoprotein concentrations with the duration of illness indicated that the protein rose to peak levels in serum as the SGOT was declining. This was confirmed by serial observations in 10 patients. Thus, the increase of alpha-fetoprotein in the sera of patients with severe hepatitis occurs as liver necrosis is subsiding. Due to other known features of alpha-fetoprotein, it is intriguing to speculate that the increase in serum levels of this protein in viral hepatitis reflects hepatic regeneration after parenchymal damage."} {"id": "PMID:163781", "title": "The hidden faces of alcoholism.", "content": "In view of the fact that 70 percent of Americans drink regularly, it is important to keep in mind that alcohol is a potent pharmacologic agent that can cause a variety of emotional and physical signs and symptoms. Physician awareness is the name of the game. Better health for patients is the reward.", "contents": "The hidden faces of alcoholism. In view of the fact that 70 percent of Americans drink regularly, it is important to keep in mind that alcohol is a potent pharmacologic agent that can cause a variety of emotional and physical signs and symptoms. Physician awareness is the name of the game. Better health for patients is the reward."} {"id": "PMID:163783", "title": "Induction of nutritional mutants of Micrococcus glutamicus and their amino acid accumulation.", "content": "Micrococcus glutamicus ATCC 13032, a glutamic acid-producing organism, was treated with 0.2M ethylmethane sulfonate, the auxotrophs isolated showing varied patterns of extracellular amino acids. Eighty auxotrophic strains were obtained, out of which 31 excreted 1.0-4.0 mg threonine per ml and all the auxotrophs required biotin for growth and production of the amino acid. Eleven auxotrophs produced 1.5 to 3.0 mg alanine per ml and these auxotrophs required amino acids for their growth. Other auxotrophs lost their excretion capacity in subsequent fermentation trials. Further mutation of the biotin-requiring auxotroph Micrococcus glutamicus EM with gamma rays resulted in the isolation of 89 auxotrophic strains, out of which 28 excreted threonine (up to 5.0 mg per ml) higher than the parent auxotroph. Exposure to X-rays yielded 97 auxotrophs, out of these 35 producing 1.0-3.0 mg methionine per ml and requiring biotin for growth and production of the amino acid. Other auxotrophs produced alanine (0.5 to 2.0 mg per ml) and threonine (2.0 to 3.3 mg per ml). Irradiation with gamma rays favoured the development of threonine producing auxotrophs while X-rays favoured methionine-producing auxotrophs.", "contents": "Induction of nutritional mutants of Micrococcus glutamicus and their amino acid accumulation. Micrococcus glutamicus ATCC 13032, a glutamic acid-producing organism, was treated with 0.2M ethylmethane sulfonate, the auxotrophs isolated showing varied patterns of extracellular amino acids. Eighty auxotrophic strains were obtained, out of which 31 excreted 1.0-4.0 mg threonine per ml and all the auxotrophs required biotin for growth and production of the amino acid. Eleven auxotrophs produced 1.5 to 3.0 mg alanine per ml and these auxotrophs required amino acids for their growth. Other auxotrophs lost their excretion capacity in subsequent fermentation trials. Further mutation of the biotin-requiring auxotroph Micrococcus glutamicus EM with gamma rays resulted in the isolation of 89 auxotrophic strains, out of which 28 excreted threonine (up to 5.0 mg per ml) higher than the parent auxotroph. Exposure to X-rays yielded 97 auxotrophs, out of these 35 producing 1.0-3.0 mg methionine per ml and requiring biotin for growth and production of the amino acid. Other auxotrophs produced alanine (0.5 to 2.0 mg per ml) and threonine (2.0 to 3.3 mg per ml). Irradiation with gamma rays favoured the development of threonine producing auxotrophs while X-rays favoured methionine-producing auxotrophs."} {"id": "PMID:163786", "title": "Effect of cyclic nucleotides on DNA synthesis in mouse lymphoid cells.", "content": "The effect of eight cyclic purine and cyclic pyrimidine nucleotides on DNA synthesis on mouse lymphoid cells was investigated. Two out of eight compounds tested, namely 2', 3'-cyclic guanosine monophosphate (2', 3'-cGMP) as well as 3', 5'-cyclic guanosine monophosphate (3', 5'-cGMP), stimulate thymidine incorporation in all types of lymphocytes tested. The stimulatory activity of the cyclic guanosine nucleotides as well as the effects of lectins could be antagonized by 3', 5'-cyclic adenosine monophosphate (3', 5'-cAMP). 2', 3'-cGMP seems to stimulate preferentially mature T-cells while 3', 5'-cGMP preferentially acts on B-cells.", "contents": "Effect of cyclic nucleotides on DNA synthesis in mouse lymphoid cells. The effect of eight cyclic purine and cyclic pyrimidine nucleotides on DNA synthesis on mouse lymphoid cells was investigated. Two out of eight compounds tested, namely 2', 3'-cyclic guanosine monophosphate (2', 3'-cGMP) as well as 3', 5'-cyclic guanosine monophosphate (3', 5'-cGMP), stimulate thymidine incorporation in all types of lymphocytes tested. The stimulatory activity of the cyclic guanosine nucleotides as well as the effects of lectins could be antagonized by 3', 5'-cyclic adenosine monophosphate (3', 5'-cAMP). 2', 3'-cGMP seems to stimulate preferentially mature T-cells while 3', 5'-cGMP preferentially acts on B-cells."} {"id": "PMID:163787", "title": "The antagonistic action of cyclic GMP and cyclic AMP on proliferation of B and T lymphocytes.", "content": "The effect of c-AMP, c-GMP and both substances together on (3H)-thymidine incorporation into nuclear DNA was investigated using spleen cells of normal and athymic nude mice. c-GMP induces DNA synthesis in both normal and nude spleen cell populations. c-AMP inhibited the stimulatory activity of c-GMP as well as the phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) response of spleen cells. The inhibitory activity of c-AMP on the PHA and LPS responses can be reversed by c-GMP. The possible role of cyclic nucleotides in the regulation of cell proliferation and of the immune response is discussed.", "contents": "The antagonistic action of cyclic GMP and cyclic AMP on proliferation of B and T lymphocytes. The effect of c-AMP, c-GMP and both substances together on (3H)-thymidine incorporation into nuclear DNA was investigated using spleen cells of normal and athymic nude mice. c-GMP induces DNA synthesis in both normal and nude spleen cell populations. c-AMP inhibited the stimulatory activity of c-GMP as well as the phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) response of spleen cells. The inhibitory activity of c-AMP on the PHA and LPS responses can be reversed by c-GMP. The possible role of cyclic nucleotides in the regulation of cell proliferation and of the immune response is discussed."} {"id": "PMID:163788", "title": "Stimulation of human lymphocytes by Herpes simplex virus antigens.", "content": "Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen.", "contents": "Stimulation of human lymphocytes by Herpes simplex virus antigens. Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen."} {"id": "PMID:163789", "title": "Characterization of an in vitro persistent-state measles virus infection: species characterization and interference in the BGM/MV cell line.", "content": "Serological methods of mixed agglutination and indirect immunofluorescence showed the BGM/MV cell line to possess monkey antigens. As a means of further characterizing the species constitution of the BGM/MV cell line, the species specificity of viral-induced interferon from these cells, as well as the response of these cells to exogenous interferons, was determined. Low titers of spontaneously elaborated interferon capable of protecting monkey but not mouse cells were detected in BGM/MV culture fluids. Interferon induced by Newcastle disease virus infection of BGM/MV cells was capable of conferring an antiviral state on monkey and, to a lesser extent, on mouse cells. Exogenous interferons of both homologous (BGM/MV) and heterologous sources failed to confer an antiviral state on BGM/MV cells. BGM/MV cells were found to be partially refractive to superinfection with measles virus but freely replicated mumps and vesicular stomatitis virus.", "contents": "Characterization of an in vitro persistent-state measles virus infection: species characterization and interference in the BGM/MV cell line. Serological methods of mixed agglutination and indirect immunofluorescence showed the BGM/MV cell line to possess monkey antigens. As a means of further characterizing the species constitution of the BGM/MV cell line, the species specificity of viral-induced interferon from these cells, as well as the response of these cells to exogenous interferons, was determined. Low titers of spontaneously elaborated interferon capable of protecting monkey but not mouse cells were detected in BGM/MV culture fluids. Interferon induced by Newcastle disease virus infection of BGM/MV cells was capable of conferring an antiviral state on monkey and, to a lesser extent, on mouse cells. Exogenous interferons of both homologous (BGM/MV) and heterologous sources failed to confer an antiviral state on BGM/MV cells. BGM/MV cells were found to be partially refractive to superinfection with measles virus but freely replicated mumps and vesicular stomatitis virus."} {"id": "PMID:163790", "title": "Antibody response to Epstein-Barr virus in infectious mononucleosis.", "content": "Altogether 171 serum specimens from 58 patients with heterophil antibody-positive infectious monomucleosis were studied for antibody response to Epstein-Barr virus (EBV). The sera were tested for fluorescent immunoglobulin G (IgG) and IgM gel-precipitating (GP) and complement-fixing (CF) antibodies to EBV. All 58 patients had IgG and IgM antibodies to EBV. Both IgG and IgM antibodies developed rapidly; the IgM antibodies disappeared within 8 to 10 weeks, whereas the IgG antibodies remained at an almost constant level. The development of IgG antibodies was so rapid that a fourfold or greater rise in titers was noted only in 22% of the patients. Both GP and CF antibodies to EBV (crude P3HR-1 Burkitt cell antigen) developed slowly; the mean titers kept rising for more than 12 weeks. The micro GP technique seemed to be more sensitive than the CF method, because 86% of the patients with infectious mononucleosis had GP antibodies compared with 72% having CF antibodies. In patients with infectious mononucleosis, a seroconversion or significant rise in GP antibodies was noted in 57%, whereas only 19% had a similar change in CF antibodies. The most promising of these antibody assays in the diagnosis of recent infections was the EBV-specific IgM antibody technique, which enables one to make the diagnosis on the basis of only one serum specimen. In cases where the acute-phase serum specimen is missing, the diagnosis can be made later by using the GP and CF techniques.", "contents": "Antibody response to Epstein-Barr virus in infectious mononucleosis. Altogether 171 serum specimens from 58 patients with heterophil antibody-positive infectious monomucleosis were studied for antibody response to Epstein-Barr virus (EBV). The sera were tested for fluorescent immunoglobulin G (IgG) and IgM gel-precipitating (GP) and complement-fixing (CF) antibodies to EBV. All 58 patients had IgG and IgM antibodies to EBV. Both IgG and IgM antibodies developed rapidly; the IgM antibodies disappeared within 8 to 10 weeks, whereas the IgG antibodies remained at an almost constant level. The development of IgG antibodies was so rapid that a fourfold or greater rise in titers was noted only in 22% of the patients. Both GP and CF antibodies to EBV (crude P3HR-1 Burkitt cell antigen) developed slowly; the mean titers kept rising for more than 12 weeks. The micro GP technique seemed to be more sensitive than the CF method, because 86% of the patients with infectious mononucleosis had GP antibodies compared with 72% having CF antibodies. In patients with infectious mononucleosis, a seroconversion or significant rise in GP antibodies was noted in 57%, whereas only 19% had a similar change in CF antibodies. The most promising of these antibody assays in the diagnosis of recent infections was the EBV-specific IgM antibody technique, which enables one to make the diagnosis on the basis of only one serum specimen. In cases where the acute-phase serum specimen is missing, the diagnosis can be made later by using the GP and CF techniques."} {"id": "PMID:163791", "title": "Virus susceptibility of mouse hemopoietic cells in vitro: inhibition of granulocyte-macrophage precursor cells by Newcastle disease virus.", "content": "Normal mouse bone marrow cells were exposed to encephalomyocarditis virus (EMC), reovirus type 3 (REO3), influenza virus (FLU), and Newcastle disease virus (NDV) then assayed for granulocyte-macrophage precursor cells by the technique of colony formation in agar. Exposure to EMC, REO3, and FLU caused a slight but variable loss of colony-forming potential, whereas exposure to NDV caused a very marked loss. NDV acted directly on the cells, not indirectly through release of colony-inhibiting factors or destruction of colony-stimulating factor. Experiments with NDV inactivated by heat, ether, or ultraviolet irradiation indicated that colony inhibition was associated with fully infective virus, even though some of the inactivated preparations had retained full hemagglutinin, neuraminidase, or hemolytic activity.", "contents": "Virus susceptibility of mouse hemopoietic cells in vitro: inhibition of granulocyte-macrophage precursor cells by Newcastle disease virus. Normal mouse bone marrow cells were exposed to encephalomyocarditis virus (EMC), reovirus type 3 (REO3), influenza virus (FLU), and Newcastle disease virus (NDV) then assayed for granulocyte-macrophage precursor cells by the technique of colony formation in agar. Exposure to EMC, REO3, and FLU caused a slight but variable loss of colony-forming potential, whereas exposure to NDV caused a very marked loss. NDV acted directly on the cells, not indirectly through release of colony-inhibiting factors or destruction of colony-stimulating factor. Experiments with NDV inactivated by heat, ether, or ultraviolet irradiation indicated that colony inhibition was associated with fully infective virus, even though some of the inactivated preparations had retained full hemagglutinin, neuraminidase, or hemolytic activity."} {"id": "PMID:163792", "title": "Escherichia coli enterotoxin: stimulation of adenylate cyclase in broken-cell preparations.", "content": "The enterotoxin from cell-free filtrates of the enteropathogenic Escherichia coli strain P-263 was found to stimulate adenylate cyclase activity in broken-cell preparations from myocardial tissue. Particulate and detergent-solubilized fractions from cat heart were incubated with enterotoxin and assayed for adenylate cyclase activity. Adenylate cyclase activity was stimulated by enterotoxin; the extent of stimulation was proportional to the concentration of enterotoxin. The data demonstrate that stimulation of enterotoxin-sensitive adenylate cyclase in this system provides a sensitive in vitro assay, either as an accurate measure of enterotoxin concentration or as an assay for antitoxic titers in sera. A parallel comparison showed that stimulation of fluid production in rabbit intestinal loops by enterotoxin was less sensitive.", "contents": "Escherichia coli enterotoxin: stimulation of adenylate cyclase in broken-cell preparations. The enterotoxin from cell-free filtrates of the enteropathogenic Escherichia coli strain P-263 was found to stimulate adenylate cyclase activity in broken-cell preparations from myocardial tissue. Particulate and detergent-solubilized fractions from cat heart were incubated with enterotoxin and assayed for adenylate cyclase activity. Adenylate cyclase activity was stimulated by enterotoxin; the extent of stimulation was proportional to the concentration of enterotoxin. The data demonstrate that stimulation of enterotoxin-sensitive adenylate cyclase in this system provides a sensitive in vitro assay, either as an accurate measure of enterotoxin concentration or as an assay for antitoxic titers in sera. A parallel comparison showed that stimulation of fluid production in rabbit intestinal loops by enterotoxin was less sensitive."} {"id": "PMID:163793", "title": "Naturally occurring persistent feline oncornavirus infections in the absence of disease.", "content": "Healthy feline leukemia virus (FeLV)-infected cats from leukemia cluster environments were followed for up to 23 months for development of disease and evidence of alteration in the hemogram. The incidence of disease development in FeLV-postive cats was more than fivefold higher than the incidence for FeLV-negative cats. Ten cases of leukemia developed in 69 infected cats, whereas one case of leukemia occurred in 59 uninfected cats. The incidence for development of diseases other than leukemia was 30.4 percent for FeLV-infected cats as opposed to 6.8 per cent for uninfected cats. This could be a result of the immunosuppressive effects of FeLV. Felv-infected cats had no evidence of subclinical anemia. Mean packed cell volumes and total leukocyte counts were about the same for infected and uninfected animals. The only variation seen in healthy FeLV-infected cats was a decreased mean lymphocyte count. The difference between mean lymphocyte count for FeLV-infected and uninfected animals was significant at the 0.999 level. These findings suggest that the incubation period for feline leukemia may be very prolonged under natural conditions and that an increased susceptibility to unrelated infectious diseases exists during this period. This increased susceptibility was apparently not associated with anemia or depressed total leukocyte counts.", "contents": "Naturally occurring persistent feline oncornavirus infections in the absence of disease. Healthy feline leukemia virus (FeLV)-infected cats from leukemia cluster environments were followed for up to 23 months for development of disease and evidence of alteration in the hemogram. The incidence of disease development in FeLV-postive cats was more than fivefold higher than the incidence for FeLV-negative cats. Ten cases of leukemia developed in 69 infected cats, whereas one case of leukemia occurred in 59 uninfected cats. The incidence for development of diseases other than leukemia was 30.4 percent for FeLV-infected cats as opposed to 6.8 per cent for uninfected cats. This could be a result of the immunosuppressive effects of FeLV. Felv-infected cats had no evidence of subclinical anemia. Mean packed cell volumes and total leukocyte counts were about the same for infected and uninfected animals. The only variation seen in healthy FeLV-infected cats was a decreased mean lymphocyte count. The difference between mean lymphocyte count for FeLV-infected and uninfected animals was significant at the 0.999 level. These findings suggest that the incubation period for feline leukemia may be very prolonged under natural conditions and that an increased susceptibility to unrelated infectious diseases exists during this period. This increased susceptibility was apparently not associated with anemia or depressed total leukocyte counts."} {"id": "PMID:163794", "title": "Genital herpesvirus hominis infection in mice. I. Development of an experimental model.", "content": "Pregnant female mice, after intravaginal inoculation with Herpesvirus hominis (HVH) type 2, developed vaginitis on days 5 to 7 after virus challenge, followed by hunching and hind limb paralysis on days 7 to 9 and death from encephalitis on days 9 to 11. After initial replication in the mucous membranes of the genital tract, virus spread to the spinal cord and ascended to involve the brain. Viremia or replication of H. hominis type 2 in the liver or spleen was not detected. Virus was cleared from vaginal secretions by days 8 to 10 after infection. Pregnant mice were more susceptible to the infection than nonpregnant mice. This experimental infection in female mice provides a model for genital herpesvirus infection and for herpesvirus infection and for herpesvirus encephalitis in which one can evaluate potentially promising antiviral chemotherapeutic agents.", "contents": "Genital herpesvirus hominis infection in mice. I. Development of an experimental model. Pregnant female mice, after intravaginal inoculation with Herpesvirus hominis (HVH) type 2, developed vaginitis on days 5 to 7 after virus challenge, followed by hunching and hind limb paralysis on days 7 to 9 and death from encephalitis on days 9 to 11. After initial replication in the mucous membranes of the genital tract, virus spread to the spinal cord and ascended to involve the brain. Viremia or replication of H. hominis type 2 in the liver or spleen was not detected. Virus was cleared from vaginal secretions by days 8 to 10 after infection. Pregnant mice were more susceptible to the infection than nonpregnant mice. This experimental infection in female mice provides a model for genital herpesvirus infection and for herpesvirus infection and for herpesvirus encephalitis in which one can evaluate potentially promising antiviral chemotherapeutic agents."} {"id": "PMID:163795", "title": "Response of irradiated mice to live-virus (TC-83) immunization.", "content": "Studies were conducted to determine the effects of sublethal, acute, total-body irradiation (600 R) on the immune response of mice to a replicating antigen. Irradiation was performed at varying times (0 to 21 days) prior to immunization with attenuated Venezuelan equine encephalomyelitis virus, TC-83. Development of protective immunity was studied by inoculating subgroups of irradiated mice with virulent Venezuelan equine encephalomyelitis virus on days 1 through 28 after immunization. Irradiation failed to affect the overt clinical response of mice inoculated with the attenuated strain, but antibody responses and the onset of protective immunity was delayed, particularly in mice irradiated 2 h to 3 days prior to vaccination. Immunity afforded by TC-83 developed more rapidly as the interval between irradiation and vaccination increased: when this interval was 14 or more days, the temporal course of immune response in irradiated mice was similar to that of nonirradiated vaccines. Persistence of TC-83 viremia was greatly prolonged in irradiated mice through the irradiation recovery period and probably provided the antigenic stimulus responsible for delayed development of effective immunity.", "contents": "Response of irradiated mice to live-virus (TC-83) immunization. Studies were conducted to determine the effects of sublethal, acute, total-body irradiation (600 R) on the immune response of mice to a replicating antigen. Irradiation was performed at varying times (0 to 21 days) prior to immunization with attenuated Venezuelan equine encephalomyelitis virus, TC-83. Development of protective immunity was studied by inoculating subgroups of irradiated mice with virulent Venezuelan equine encephalomyelitis virus on days 1 through 28 after immunization. Irradiation failed to affect the overt clinical response of mice inoculated with the attenuated strain, but antibody responses and the onset of protective immunity was delayed, particularly in mice irradiated 2 h to 3 days prior to vaccination. Immunity afforded by TC-83 developed more rapidly as the interval between irradiation and vaccination increased: when this interval was 14 or more days, the temporal course of immune response in irradiated mice was similar to that of nonirradiated vaccines. Persistence of TC-83 viremia was greatly prolonged in irradiated mice through the irradiation recovery period and probably provided the antigenic stimulus responsible for delayed development of effective immunity."} {"id": "PMID:163796", "title": "Defense mechanisms against infectious bovine rhinotracheitis virus: inhibition of virus infection by murine macrophages.", "content": "An in vitro method is described to measure the inhibitory activity of murine peritoneal exudate cells against viral plaque formation by a bovine herpes-virus-infectious bovin'e rhinotracheitis virus. Microtiter plates containing 96 bovine kidney cell monolayers were infected with a range of virus concentration and peritoneal exudate cells were subsequently added. When a sufficient number of cells was added, viral plaques were not detectable and free infectious virus did not occur in the culture fluids. The inhibitory cell type adhered to glass and was presumably a macrohage. Although inhibitory of viral plaques was presumably a macrophage. Although inhibition of viral plaques was complete and free virus could not be detected, virus was not eliminated from the monolayers since on removal of cells, the degree of virus cytopathology and yield of virus after a further 48 h of incubation was the same as in 48-h infected control monolayers. The significance of peritoneal exudate-cells-induced virus suppression as a model to understand herpesvirus latency is briefly discussed.?Author", "contents": "Defense mechanisms against infectious bovine rhinotracheitis virus: inhibition of virus infection by murine macrophages. An in vitro method is described to measure the inhibitory activity of murine peritoneal exudate cells against viral plaque formation by a bovine herpes-virus-infectious bovin'e rhinotracheitis virus. Microtiter plates containing 96 bovine kidney cell monolayers were infected with a range of virus concentration and peritoneal exudate cells were subsequently added. When a sufficient number of cells was added, viral plaques were not detectable and free infectious virus did not occur in the culture fluids. The inhibitory cell type adhered to glass and was presumably a macrohage. Although inhibitory of viral plaques was presumably a macrophage. Although inhibition of viral plaques was complete and free virus could not be detected, virus was not eliminated from the monolayers since on removal of cells, the degree of virus cytopathology and yield of virus after a further 48 h of incubation was the same as in 48-h infected control monolayers. The significance of peritoneal exudate-cells-induced virus suppression as a model to understand herpesvirus latency is briefly discussed.?Author"} {"id": "PMID:163797", "title": "Analysis of unidirectional fluxes of sodium during diarrhea induced by Clostridium perfringens enterotoxin in the rat terminal ileum.", "content": "Net intestinal transport of sodium in vivo, in control and enterotoxin (Clostridium perfringens)-treated rats, was resolved into two unidirectional fluxes, influx from and efflux into the lumen of the terminal ileum. In rats treated with the toxin, sodium influx remained similar to control values even during fluid and electrolyte loss to the lumen. Net loss of sodium was shown to be due to nearly a twofold increase in sodium efflux to the lumen in toxin-treated animals. There was only slight histopathological damage to the mucosa, especially noticeable at the tips of villi.", "contents": "Analysis of unidirectional fluxes of sodium during diarrhea induced by Clostridium perfringens enterotoxin in the rat terminal ileum. Net intestinal transport of sodium in vivo, in control and enterotoxin (Clostridium perfringens)-treated rats, was resolved into two unidirectional fluxes, influx from and efflux into the lumen of the terminal ileum. In rats treated with the toxin, sodium influx remained similar to control values even during fluid and electrolyte loss to the lumen. Net loss of sodium was shown to be due to nearly a twofold increase in sodium efflux to the lumen in toxin-treated animals. There was only slight histopathological damage to the mucosa, especially noticeable at the tips of villi."} {"id": "PMID:163798", "title": "Adenovirus-transformed cells restrict Herpes simplex virus replication.", "content": "A cell line that normally supports the replication of herpes simplex virus types 1 and 2 became resistant to these viruses after transformation by simian adenovirus 7. Kinetic studies of the mechanism of resistance demonstrated that both herpesviruses were able to attach to the transformed cells and express some early genomic functions, as demonstrated by the presence of low levels of viral thymidine kinase. However, isopycnic centrifugation studies of the abortive system failed to detect viral deoxyribonucleic acid synthesis, whereas indirect immunofluorescent studies of viral proteins revealed that less than 10 per cent of the cells contained these viral macromolecules at any given time. Collectively the data suggest that after transformation by simian adenovirus 7 these cells are altered so as to render them resistant or incapable of supporting the growth of herpes simplex virus types 1 and 2. The results further suggest that the block occurs after viral absorption and prior to viral deoxyribonucleic acid synthesis.", "contents": "Adenovirus-transformed cells restrict Herpes simplex virus replication. A cell line that normally supports the replication of herpes simplex virus types 1 and 2 became resistant to these viruses after transformation by simian adenovirus 7. Kinetic studies of the mechanism of resistance demonstrated that both herpesviruses were able to attach to the transformed cells and express some early genomic functions, as demonstrated by the presence of low levels of viral thymidine kinase. However, isopycnic centrifugation studies of the abortive system failed to detect viral deoxyribonucleic acid synthesis, whereas indirect immunofluorescent studies of viral proteins revealed that less than 10 per cent of the cells contained these viral macromolecules at any given time. Collectively the data suggest that after transformation by simian adenovirus 7 these cells are altered so as to render them resistant or incapable of supporting the growth of herpes simplex virus types 1 and 2. The results further suggest that the block occurs after viral absorption and prior to viral deoxyribonucleic acid synthesis."} {"id": "PMID:163799", "title": "Enterotoxin formation by different toxigenic types of Clostridium perfringens.", "content": "Sixty-nine strains of Clostridium perfringens of different toxigenic types were investigated for enterotoxin production. Enterotoxin was definitively detected only in strains of types A and C. This is the first report where enterotoxin production has been demonstrated in a toxigenic type other than type A. The exterotoxin-positive type C strains were isolated from cases of enteritis necroticans (\"pig bel+) in New Guinea. The major enterotoxin from type C showed a reaction of complete identity with enterotoxin from type A in immunodiffusion using anti-enterotoxin serum prepared against the latter; it induced erythema when injected intradermally into depilated guinea pigs and caused fluid accumulation in the rabbit ileal loop. The results indicate that the major enterotoxin from type C was serologically and biologically similar to enterotoxin from type A. In some C was serologically and biologically similar to enterotoxin from type A. In some type C strains, an enterotoxin was detected that showed a reaction of partial serological identity. Spore coat proteins were extracted from 14-strains by alkaline dithiothreitol, and the extracts were assayed for enterotoxin-like spore protein. Enterotoxin could be extracted from type A and type C spores, and all positive strains showed a reaction of complete identity in immunodiffusion with enterotoxin obtained from cell extracts of type A. Disc immunoelectrophoresis demonstrated that two distinct components that reacted serologically with anti-enterotoxin serum were present in both the cell extract and in extracted spore protein from one type C strain. These distinct components differed in molecular weight.", "contents": "Enterotoxin formation by different toxigenic types of Clostridium perfringens. Sixty-nine strains of Clostridium perfringens of different toxigenic types were investigated for enterotoxin production. Enterotoxin was definitively detected only in strains of types A and C. This is the first report where enterotoxin production has been demonstrated in a toxigenic type other than type A. The exterotoxin-positive type C strains were isolated from cases of enteritis necroticans (\"pig bel+) in New Guinea. The major enterotoxin from type C showed a reaction of complete identity with enterotoxin from type A in immunodiffusion using anti-enterotoxin serum prepared against the latter; it induced erythema when injected intradermally into depilated guinea pigs and caused fluid accumulation in the rabbit ileal loop. The results indicate that the major enterotoxin from type C was serologically and biologically similar to enterotoxin from type A. In some C was serologically and biologically similar to enterotoxin from type A. In some type C strains, an enterotoxin was detected that showed a reaction of partial serological identity. Spore coat proteins were extracted from 14-strains by alkaline dithiothreitol, and the extracts were assayed for enterotoxin-like spore protein. Enterotoxin could be extracted from type A and type C spores, and all positive strains showed a reaction of complete identity in immunodiffusion with enterotoxin obtained from cell extracts of type A. Disc immunoelectrophoresis demonstrated that two distinct components that reacted serologically with anti-enterotoxin serum were present in both the cell extract and in extracted spore protein from one type C strain. These distinct components differed in molecular weight."} {"id": "PMID:163800", "title": "Effect of immunosuppression on the genetic resistance of A2G mice to neurovirulent influenza virus.", "content": "A2G mice are genetically resistant to lethal infection with neurotropic and pneumotropic influenza viruses. A possible immunological explanation for this resistance was sought by assessing the effect of cyclophosphamide and X irradiation immunosuppression on the infection of A2G mice with lethal doses of neurovirulent virus. Immunosuppressed A2G mice survived lethal infection enen though rendered unable to produce specific antiviral antibody or to generate cell-mediated delayed-type hypersensitivity responses. Measurement of infectious virus replication and detailed observation of the infection by immunofluorescence microscopy show that immunosuppression does not potentiate or allow spread of the virus in A2G brains. Interferon levels were essentially the same in normal and immunosuppressed A2G brains but were 3 to 5 times lower than in the brains of susceptible mice dying of the infection. The results strongly suggest that the genetic resistance of A2G mice to the acute lethal effects of neurovirulent influenza virus infection does not depend on the induction of primary immune mechanisms as we currently understand them. Other possible explanations for this resistance are considered.", "contents": "Effect of immunosuppression on the genetic resistance of A2G mice to neurovirulent influenza virus. A2G mice are genetically resistant to lethal infection with neurotropic and pneumotropic influenza viruses. A possible immunological explanation for this resistance was sought by assessing the effect of cyclophosphamide and X irradiation immunosuppression on the infection of A2G mice with lethal doses of neurovirulent virus. Immunosuppressed A2G mice survived lethal infection enen though rendered unable to produce specific antiviral antibody or to generate cell-mediated delayed-type hypersensitivity responses. Measurement of infectious virus replication and detailed observation of the infection by immunofluorescence microscopy show that immunosuppression does not potentiate or allow spread of the virus in A2G brains. Interferon levels were essentially the same in normal and immunosuppressed A2G brains but were 3 to 5 times lower than in the brains of susceptible mice dying of the infection. The results strongly suggest that the genetic resistance of A2G mice to the acute lethal effects of neurovirulent influenza virus infection does not depend on the induction of primary immune mechanisms as we currently understand them. Other possible explanations for this resistance are considered."} {"id": "PMID:163801", "title": "Effect of Mycoplasma pneumoniae on poliovirus replication.", "content": "Results are presented which indicate that different species of mycoplasma may have varying effects on the replication of different viral types.", "contents": "Effect of Mycoplasma pneumoniae on poliovirus replication. Results are presented which indicate that different species of mycoplasma may have varying effects on the replication of different viral types."} {"id": "PMID:163802", "title": "Immunological comparison of various human pregnancy-associated plasma proteins.", "content": "Direct immunodiffusion comparison with specific antisera demonstrated that all of the four pregnancy-associated plasma proteins (PAPPs) described in our laboratory are distinct from the pregnancy zone protein (von Schoultz); alpha2-pregnoglobulin (Berne); pregnancy-associated alpha2-glycoprotein (SP3) (Bohn); new serum alpha2-macroglobulin (Stimson); PAG (Horne); pregnancy-associated alpha2-globulin (Kasukawa); Pal (McLaren), and Xh protein (Dunston). All the latter proved to be immunologically idnetical to each other, and apparently represent the same protein described under different names. It was confirmed that none of the PAPPs is immunochemically related to placental alkaline phosphatase. PAPP-A, PAPP-C, and the pregnancy zone protein, but not HPL (PAPP-D), showed a decreased anodic mobility when treated with neuraminidase; their reactivities with antibody were essentially unaffected by the ezyme, however. Certain detergents had no effect on the immunological reactivities of the PAPPs and the pregnancy zone protein in whole plasma, while butanol and desoxycholate partially, and urea, SDS and cetylpyridinium largely inactivated them.", "contents": "Immunological comparison of various human pregnancy-associated plasma proteins. Direct immunodiffusion comparison with specific antisera demonstrated that all of the four pregnancy-associated plasma proteins (PAPPs) described in our laboratory are distinct from the pregnancy zone protein (von Schoultz); alpha2-pregnoglobulin (Berne); pregnancy-associated alpha2-glycoprotein (SP3) (Bohn); new serum alpha2-macroglobulin (Stimson); PAG (Horne); pregnancy-associated alpha2-globulin (Kasukawa); Pal (McLaren), and Xh protein (Dunston). All the latter proved to be immunologically idnetical to each other, and apparently represent the same protein described under different names. It was confirmed that none of the PAPPs is immunochemically related to placental alkaline phosphatase. PAPP-A, PAPP-C, and the pregnancy zone protein, but not HPL (PAPP-D), showed a decreased anodic mobility when treated with neuraminidase; their reactivities with antibody were essentially unaffected by the ezyme, however. Certain detergents had no effect on the immunological reactivities of the PAPPs and the pregnancy zone protein in whole plasma, while butanol and desoxycholate partially, and urea, SDS and cetylpyridinium largely inactivated them."} {"id": "PMID:163803", "title": "Further studies on the inheritance of responsiveness to pertussis HSF in mice.", "content": "Inheritance of responsiveness to histamine-sensitizing factor of pertussis bacilli (HSF) was investigated in (C3H/HeJ times C57BL/6J)F1 hybrids, backcross progeny of this hybrid to C57BJ/6J parent (C3H/HeJ times DBA/2J)F1 hybrids, and in backcross progeny of this hybrid to DBA/2J parent. It was found that transmission is not by virtue of a single autosomal dominant gene, as has been postulated. Rather, inheritance of responsiveness to HSF is far more complex, probably involving polygenic transmission.", "contents": "Further studies on the inheritance of responsiveness to pertussis HSF in mice. Inheritance of responsiveness to histamine-sensitizing factor of pertussis bacilli (HSF) was investigated in (C3H/HeJ times C57BL/6J)F1 hybrids, backcross progeny of this hybrid to C57BJ/6J parent (C3H/HeJ times DBA/2J)F1 hybrids, and in backcross progeny of this hybrid to DBA/2J parent. It was found that transmission is not by virtue of a single autosomal dominant gene, as has been postulated. Rather, inheritance of responsiveness to HSF is far more complex, probably involving polygenic transmission."} {"id": "PMID:163806", "title": "The action of ionizing radiation on protein: radical formation in L-histidine crystals.", "content": "Radicals produced at temperatures between 77 K and 300 K by X-irradiation of L-histidine.2HC1 crystals have been analysed by electron spin resonance spectroscopy. The results are compared with previous findings with L-histidine and L-histidine.HC1.H2O crystals. In these three crystals we have identified three main species, which, depending on the molecular environment, are stabilized at different temperatures and produced in different concentrations. These findings are discussed in connection with the observations made on irradiated aqueous solutions of amino acids. It is concluded that our results corroborate the mechanism for the action of ionizing radiation on dry protein proposed by Platzman and Franck (1958),", "contents": "The action of ionizing radiation on protein: radical formation in L-histidine crystals. Radicals produced at temperatures between 77 K and 300 K by X-irradiation of L-histidine.2HC1 crystals have been analysed by electron spin resonance spectroscopy. The results are compared with previous findings with L-histidine and L-histidine.HC1.H2O crystals. In these three crystals we have identified three main species, which, depending on the molecular environment, are stabilized at different temperatures and produced in different concentrations. These findings are discussed in connection with the observations made on irradiated aqueous solutions of amino acids. It is concluded that our results corroborate the mechanism for the action of ionizing radiation on dry protein proposed by Platzman and Franck (1958),"} {"id": "PMID:163808", "title": "Sensitivity of glucose 6-phosphatase activity to glutaraldehyde.", "content": "The effect of glutaraldehyde fixation on glucose 6-phosphatase activity in mouse liver was investigated. After transparenchymal perfusion with 2% glutaraldehyde for 1.5 minutes, the activity of the recovered enzyme was higher than those reported for acid phosphatase and aryl sulfatase activities after fixation under similar condition, and an abundant deposition of reaction product was observed in hepatocytes. Subsequent immersion in the same fixative solution for 30 minutes after 4 degrees C resulted in only a slight decrease in the activity. However, the activity was almost completely destroyed after 3 hours of immersion fixation at 4 degrees C following the perfusion. Therefore, the enzyme can be said to be aldehyde-sensitive when a long fixation time is used, but not aldehyde-sensitive during a short fixation time.", "contents": "Sensitivity of glucose 6-phosphatase activity to glutaraldehyde. The effect of glutaraldehyde fixation on glucose 6-phosphatase activity in mouse liver was investigated. After transparenchymal perfusion with 2% glutaraldehyde for 1.5 minutes, the activity of the recovered enzyme was higher than those reported for acid phosphatase and aryl sulfatase activities after fixation under similar condition, and an abundant deposition of reaction product was observed in hepatocytes. Subsequent immersion in the same fixative solution for 30 minutes after 4 degrees C resulted in only a slight decrease in the activity. However, the activity was almost completely destroyed after 3 hours of immersion fixation at 4 degrees C following the perfusion. Therefore, the enzyme can be said to be aldehyde-sensitive when a long fixation time is used, but not aldehyde-sensitive during a short fixation time."} {"id": "PMID:163810", "title": "Isolation of a metabolite capable of differentially supporting the growth of nicotinamide adenine dinucleotide auxotrophs of Escherichia coli.", "content": "A compound, isolated from the culture fluid of a nadC auxotroph of Escherichia coli grown in a minimal medium, supports the growth of both a nadA and a nadB mutant. This metabolite exhibits an ultraviolet light absorption spectrum and a mass spectrum, different from quinolinic acid. This compound may be the precursor of quinolinic acid, an intermediate in the biosynthesis of nicotinamide adenosine dinucleotide.", "contents": "Isolation of a metabolite capable of differentially supporting the growth of nicotinamide adenine dinucleotide auxotrophs of Escherichia coli. A compound, isolated from the culture fluid of a nadC auxotroph of Escherichia coli grown in a minimal medium, supports the growth of both a nadA and a nadB mutant. This metabolite exhibits an ultraviolet light absorption spectrum and a mass spectrum, different from quinolinic acid. This compound may be the precursor of quinolinic acid, an intermediate in the biosynthesis of nicotinamide adenosine dinucleotide."} {"id": "PMID:163811", "title": "Isolation and characterization of catabolite-resistant mutants in the D-serine deaminase system of Escherichia coli K-12.", "content": "Two classes of D-serine deaminase (Dsdase)-specific secondary mutants of Escherichia coli K-12 were isolated from a Dsdase low constitutive nonhyperinducible mutant as types which could grow in the presence of both D-serine and glucose. These strains contain cis dominant, nonsuppressible mutations in the dsdO (operator-initiator) region. In the first class of mutants (e.g., FB4010), Dsdase synthesis is completely insensitive to catabolite repression, and synthesis occurs at a high constitutive rate in the absence of cyclic adenosine 5'-monophosphate. In the second class (e.g., FB4005), Dsdase synthesis is partially insensitive to catabolite repression, and catabolite repression is reversed by the addition of cyclic adenosine 5'-monophosphate. Dsdase synthesis in strain FB4005 is partially independent of the cyclic adenosine 5'-monophosphate binding protein, as constitutive synthesis is reduced only 65% (relative to the cap+ strain) in strains unable to synthesize the cyclic adenosine 5'-monophosphate binding protein. Surprisingly, the constitutive rate of Dsdase synthesis is fourfold higher in all mutants of both classes than in the parent, indicating a close interrelationship between the sites of response to induction and catabolite repression.", "contents": "Isolation and characterization of catabolite-resistant mutants in the D-serine deaminase system of Escherichia coli K-12. Two classes of D-serine deaminase (Dsdase)-specific secondary mutants of Escherichia coli K-12 were isolated from a Dsdase low constitutive nonhyperinducible mutant as types which could grow in the presence of both D-serine and glucose. These strains contain cis dominant, nonsuppressible mutations in the dsdO (operator-initiator) region. In the first class of mutants (e.g., FB4010), Dsdase synthesis is completely insensitive to catabolite repression, and synthesis occurs at a high constitutive rate in the absence of cyclic adenosine 5'-monophosphate. In the second class (e.g., FB4005), Dsdase synthesis is partially insensitive to catabolite repression, and catabolite repression is reversed by the addition of cyclic adenosine 5'-monophosphate. Dsdase synthesis in strain FB4005 is partially independent of the cyclic adenosine 5'-monophosphate binding protein, as constitutive synthesis is reduced only 65% (relative to the cap+ strain) in strains unable to synthesize the cyclic adenosine 5'-monophosphate binding protein. Surprisingly, the constitutive rate of Dsdase synthesis is fourfold higher in all mutants of both classes than in the parent, indicating a close interrelationship between the sites of response to induction and catabolite repression."} {"id": "PMID:163812", "title": "Effect of tsl mutations in decreasing radiation sensitivity of a recA- strain of Escherichia coli K-12.", "content": "It has been shown previously that the radiation sensitivity of lexA- strains of Escherichia coli K-12 can be suppressed by thermosensitive mutations (designated tsl) that are closely linked to the lexA locus and are thought to be intragenic suppressors of lexA mutations (Mount et al., 1973). When a recA mutation is crossed into a suppressed tsl- strain, the extreme radiation sensitivity usually conferred by a recA mutation is decreased, but there is no detectable change in genetic recombination deficiency. Increased resistance to UV in the tsl-reA-strains depends upon ability to synthesize active uvrA+ product.", "contents": "Effect of tsl mutations in decreasing radiation sensitivity of a recA- strain of Escherichia coli K-12. It has been shown previously that the radiation sensitivity of lexA- strains of Escherichia coli K-12 can be suppressed by thermosensitive mutations (designated tsl) that are closely linked to the lexA locus and are thought to be intragenic suppressors of lexA mutations (Mount et al., 1973). When a recA mutation is crossed into a suppressed tsl- strain, the extreme radiation sensitivity usually conferred by a recA mutation is decreased, but there is no detectable change in genetic recombination deficiency. Increased resistance to UV in the tsl-reA-strains depends upon ability to synthesize active uvrA+ product."} {"id": "PMID:163813", "title": "Isolation of a catabolite repression mutant of yeast as a revertant of a strain that is maltose negative in the respiratory-deficient state.", "content": "A character originating from Saccharomyces cerevisiae 1403-7A is described which interferes with maltose growth in the respiratory-deficient state. This character is inherited in an apparently non-Mendelian way, but at present no statement can be made concerning the localization of this character on a plasmid or the involvement of multiple genes. As a revertant of this character, a flaky mutant was isolated, showing a heavy flocculation during growth on liquid medium and resistance to catabolite repression for maltase, alpha-methyl-glucosidase, invertase, and succinate dehydrogenase. In wild-type cells, repression (caused by growth on 2% glucose) and derepression (caused by growth on 2% galactose) can be correlated with a lower and a higher level of cyclic 3',5'-adenosine monophosphate (cAMP), respectively. In cells of flaky mutant, growth on these carbon sources results in the same levels of cAMP as observed for the wild type. Consequently, in this mutant derepression in the presence of 2% glucose is not reflected in a higher level of cAMP.", "contents": "Isolation of a catabolite repression mutant of yeast as a revertant of a strain that is maltose negative in the respiratory-deficient state. A character originating from Saccharomyces cerevisiae 1403-7A is described which interferes with maltose growth in the respiratory-deficient state. This character is inherited in an apparently non-Mendelian way, but at present no statement can be made concerning the localization of this character on a plasmid or the involvement of multiple genes. As a revertant of this character, a flaky mutant was isolated, showing a heavy flocculation during growth on liquid medium and resistance to catabolite repression for maltase, alpha-methyl-glucosidase, invertase, and succinate dehydrogenase. In wild-type cells, repression (caused by growth on 2% glucose) and derepression (caused by growth on 2% galactose) can be correlated with a lower and a higher level of cyclic 3',5'-adenosine monophosphate (cAMP), respectively. In cells of flaky mutant, growth on these carbon sources results in the same levels of cAMP as observed for the wild type. Consequently, in this mutant derepression in the presence of 2% glucose is not reflected in a higher level of cAMP."} {"id": "PMID:163814", "title": "Control of expression of the pyr genes in Salmonella typhimurium: effects of variations in uridine and cytidine nucleotide pools.", "content": "The differential rate of synthesis of five of the pyrimidine biosynthetic enzymes coded for by pyrB-F, and the endogenous concentrations of the individual pyrimidine nucleotides were determined in specially constructed mutants of Salmonella typhimurium. In the mutants employed the different pyrimidine nucleotide pools may be manipulated individually during exponential growth. The results obtained indicate the following. (i) The expression of pyrB, pyrE, and pyrF is controlled by a uridine nucleotide in a noncoordinate manner. (ii) The expression of pyrC and pyrD is regulated predominantly by a cytidine nucleotide. Under all conditions investigated, their expression seems to be coordinated, even though the genes are not contiguous on the chromosome. (iii) The low-molecular-weight effectors involved in controlling the expression of the pyr genes are neither uridine 5'-monophosphate nor cytidine 5'-monophosphate, but rather the corresponding di- or triphosphates.", "contents": "Control of expression of the pyr genes in Salmonella typhimurium: effects of variations in uridine and cytidine nucleotide pools. The differential rate of synthesis of five of the pyrimidine biosynthetic enzymes coded for by pyrB-F, and the endogenous concentrations of the individual pyrimidine nucleotides were determined in specially constructed mutants of Salmonella typhimurium. In the mutants employed the different pyrimidine nucleotide pools may be manipulated individually during exponential growth. The results obtained indicate the following. (i) The expression of pyrB, pyrE, and pyrF is controlled by a uridine nucleotide in a noncoordinate manner. (ii) The expression of pyrC and pyrD is regulated predominantly by a cytidine nucleotide. Under all conditions investigated, their expression seems to be coordinated, even though the genes are not contiguous on the chromosome. (iii) The low-molecular-weight effectors involved in controlling the expression of the pyr genes are neither uridine 5'-monophosphate nor cytidine 5'-monophosphate, but rather the corresponding di- or triphosphates."} {"id": "PMID:163815", "title": "Regulatory factors affecting alpha-amylase production in bacillus licheniformis.", "content": "Possible factors regulating alpha-mylase synthesis in wild-type Bacillus licheniformis and in mutants producing elevated levels of the enzyme were studied in terms of catabolite repression, apparent temperature-sensitive repression, induction, and culture age. The synthesis of alpha-amylase in the parent strain occurred long after the culture reached the stationary phase of growth as a result of de novo protein synthesis, occurred only at high temperature around 50 C and not below 45 C, appeared to be induced in the presence of oligosaccharides with some linkage of alpha-1,4-, beta-1,4, beta-1,6-glucosyl glucose, or alpha-1,6-galactosyl glucose, and was repressed by the addition of exogenous glucose or low-molecular-weight metabolites. The addition of cyclic adenosine 3',5'-monophosphate stimulated alpha-amylase accumulation in growing cultures of the parent strain, but neither shortened the long lap period prior to the start of alpha-amylase synthesis nor mitigated the repressive effect of glucose. Mutant strains derived from the parent strain showed variation in the pattern of alpha-amylase synthesis, and some of them such as F-12s and F-14 produced alpha-amylase constitutively and without sensitivity to catabolite repression or transient repression from the moment of cell growth. These results are discussed in relation to possible regulatory mechanisms that might account for the observed characteristics of alpha-amylase synthesis in this facultative thermophilic microorganism.", "contents": "Regulatory factors affecting alpha-amylase production in bacillus licheniformis. Possible factors regulating alpha-mylase synthesis in wild-type Bacillus licheniformis and in mutants producing elevated levels of the enzyme were studied in terms of catabolite repression, apparent temperature-sensitive repression, induction, and culture age. The synthesis of alpha-amylase in the parent strain occurred long after the culture reached the stationary phase of growth as a result of de novo protein synthesis, occurred only at high temperature around 50 C and not below 45 C, appeared to be induced in the presence of oligosaccharides with some linkage of alpha-1,4-, beta-1,4, beta-1,6-glucosyl glucose, or alpha-1,6-galactosyl glucose, and was repressed by the addition of exogenous glucose or low-molecular-weight metabolites. The addition of cyclic adenosine 3',5'-monophosphate stimulated alpha-amylase accumulation in growing cultures of the parent strain, but neither shortened the long lap period prior to the start of alpha-amylase synthesis nor mitigated the repressive effect of glucose. Mutant strains derived from the parent strain showed variation in the pattern of alpha-amylase synthesis, and some of them such as F-12s and F-14 produced alpha-amylase constitutively and without sensitivity to catabolite repression or transient repression from the moment of cell growth. These results are discussed in relation to possible regulatory mechanisms that might account for the observed characteristics of alpha-amylase synthesis in this facultative thermophilic microorganism."} {"id": "PMID:163816", "title": "Kinectics of beta-galactosidase synthesis in Escherichia coli at 5 C.", "content": "The defect in protein synthesis that is observed in Escherichia coli after transfer to low temperature was studied. For the enzyme beta-galactosidase, the elongation reactions of transcription and translation can take place slowly but normally at 5 C. The time necessary to complete the coupled synthesis of the beta-galactosidase messenger ribonucleic acid and polypeptide chain was found to be about 80 min at 5 C. From this result and from the known length of the beta-galactosidase monomer, it is possible to calculate that at 5 C one amino acid is added to the growing polypeptide chain every 4 s. The initiation of transcription of the beta-galactosidase messenger is inhibited after transfer to 5 C. This fact alone, however, cannot account for all of the phenomena observed at 5 C, because a given amount of messenger yields less enzyme at 5 C than it does at 37 C. Furthermore, in cells induced for short periods at 37 C, the capacity to synthesize beta-galactosidase after transfer to 5 C was found to accumulate linearily with the square of the time of induction. Two alternative models could account for these data. If all ribosomes that initiate translation at 37 C yield complete beta-galactosidase polypeptide chains at 5 C, then an inhibition of translation initiation after transfer to 5 C must be invoked to explain the results. If, on the other hand, a substantial portion of the ribosomes that initiate translation at 37 C do not yield complete beta-galactosidase polypeptides at 5 C, then intracistronic polarity could account for the data, and there is no need to invoke an inhibition of translation initiation at 5 C.", "contents": "Kinectics of beta-galactosidase synthesis in Escherichia coli at 5 C. The defect in protein synthesis that is observed in Escherichia coli after transfer to low temperature was studied. For the enzyme beta-galactosidase, the elongation reactions of transcription and translation can take place slowly but normally at 5 C. The time necessary to complete the coupled synthesis of the beta-galactosidase messenger ribonucleic acid and polypeptide chain was found to be about 80 min at 5 C. From this result and from the known length of the beta-galactosidase monomer, it is possible to calculate that at 5 C one amino acid is added to the growing polypeptide chain every 4 s. The initiation of transcription of the beta-galactosidase messenger is inhibited after transfer to 5 C. This fact alone, however, cannot account for all of the phenomena observed at 5 C, because a given amount of messenger yields less enzyme at 5 C than it does at 37 C. Furthermore, in cells induced for short periods at 37 C, the capacity to synthesize beta-galactosidase after transfer to 5 C was found to accumulate linearily with the square of the time of induction. Two alternative models could account for these data. If all ribosomes that initiate translation at 37 C yield complete beta-galactosidase polypeptide chains at 5 C, then an inhibition of translation initiation after transfer to 5 C must be invoked to explain the results. If, on the other hand, a substantial portion of the ribosomes that initiate translation at 37 C do not yield complete beta-galactosidase polypeptides at 5 C, then intracistronic polarity could account for the data, and there is no need to invoke an inhibition of translation initiation at 5 C."} {"id": "PMID:163817", "title": "6-Phosphogluconate dehydratase deficiency in pleiotropic carbohydrate-negative mutant strains of Pseudomonas aeruginosa.", "content": "Mutants of Pseudomonas aeruginosa, strain PAO, have been isolated that are unable to grow on mannitol, glucose, gluconate, or 2-ketogluconate, cut that exhibit wild-type growth on pyruvate, lactate, citrate, succinate, or acetate. Although some of these mutants were also unable to grow on glycerol, the mutations formed a single linkage group by quantitative transductional analysis with phage F116 on glucose minimal agar medium. Cell extracts of all mutant strains were either lacking or severely deficient in 6-phosphogluconate dehydratase activity. Glu+ transductants derived from mutant strains that retained the wild-type ability for growth at the expense of glycerol also regained the ability to grow on all C-6 compounds. Although a role for the pentose phosphate pathway in the catabolism of C6 substrates was not found, a functional Entner-Doudoroff pathway appears to be essential for the catabolism of mannitol, glucose, gluconate, and 2-ketogluconate.", "contents": "6-Phosphogluconate dehydratase deficiency in pleiotropic carbohydrate-negative mutant strains of Pseudomonas aeruginosa. Mutants of Pseudomonas aeruginosa, strain PAO, have been isolated that are unable to grow on mannitol, glucose, gluconate, or 2-ketogluconate, cut that exhibit wild-type growth on pyruvate, lactate, citrate, succinate, or acetate. Although some of these mutants were also unable to grow on glycerol, the mutations formed a single linkage group by quantitative transductional analysis with phage F116 on glucose minimal agar medium. Cell extracts of all mutant strains were either lacking or severely deficient in 6-phosphogluconate dehydratase activity. Glu+ transductants derived from mutant strains that retained the wild-type ability for growth at the expense of glycerol also regained the ability to grow on all C-6 compounds. Although a role for the pentose phosphate pathway in the catabolism of C6 substrates was not found, a functional Entner-Doudoroff pathway appears to be essential for the catabolism of mannitol, glucose, gluconate, and 2-ketogluconate."} {"id": "PMID:163818", "title": "Biosynthesis of branched-chain amino acids in yeast: effect of carbon source on leucine biosynthetic enzymes.", "content": "The three enzymes in the leucine biosynthetic pathway of yeast do not exhibit coordinate repression and derepression in response to the carbon source available in the culture medium. Growth in an acetate medium results in derepression of the first enzyme in the pathway, alpha-isopropylmalate synthase, and repression of the second two enzymes, alpha-isopropylmalate isomerase and beta-isopropylmalate dehydrogenase, relative to the levels found in glucose-grown cells. The role of endogenous leucine pools as a mediator of these differences was investigated. The leucine pools did not differ significantly between acetate-grown and glucose-grown cells. However, an elevated endogenous leucine pool, caused by exogenous leucine in the growth medium, did decrease the rate of decay of alpha-isopropylmalate synthase activity observed when acetate-grown cells were shifted to glucose. Evidence is provided suggesting that an elevated endogenous leucine pool may increase the in vivo stability of alpha-isopropylmalate synthase under several different conditions. Studies on the kinetics of alpha-isopropylmalate synthase decay in vivo and sensitivity to leucine inhibition indicate that there are two classes of the enzyme in acetate-grown yeast cells.", "contents": "Biosynthesis of branched-chain amino acids in yeast: effect of carbon source on leucine biosynthetic enzymes. The three enzymes in the leucine biosynthetic pathway of yeast do not exhibit coordinate repression and derepression in response to the carbon source available in the culture medium. Growth in an acetate medium results in derepression of the first enzyme in the pathway, alpha-isopropylmalate synthase, and repression of the second two enzymes, alpha-isopropylmalate isomerase and beta-isopropylmalate dehydrogenase, relative to the levels found in glucose-grown cells. The role of endogenous leucine pools as a mediator of these differences was investigated. The leucine pools did not differ significantly between acetate-grown and glucose-grown cells. However, an elevated endogenous leucine pool, caused by exogenous leucine in the growth medium, did decrease the rate of decay of alpha-isopropylmalate synthase activity observed when acetate-grown cells were shifted to glucose. Evidence is provided suggesting that an elevated endogenous leucine pool may increase the in vivo stability of alpha-isopropylmalate synthase under several different conditions. Studies on the kinetics of alpha-isopropylmalate synthase decay in vivo and sensitivity to leucine inhibition indicate that there are two classes of the enzyme in acetate-grown yeast cells."} {"id": "PMID:163819", "title": "Regulation of dihydrodipicolinate synthase and aspartate kinase in Bacillus subtilis.", "content": "The regulation of dihydrodipicolinate synthase (EC 4.2.1.52) and aspartate kinase (EC 2.7.2.4) was studied in Bacillus subtilis 168. Starvation for lysine gave depression of one aspartate kinase isoenzyme but not of dihydrodipicolinate synthase. Strains resistant to growth inhibition by the lysine analogue thiosine exhibited constitutively derepressed synthesis of one aspartate kinase isoenzyme but had normal levels of dihydrodipicolinate synthase. The data provide strong evidence that lysine is not the signal for derepression of dihydrodipicolinate synthase. Nevertheless, dihydrodipicolinate synthase specific activity increased during sporulation, and it is suggested that this increase may result, in part, from resistance to proteolysis of that enzyme.", "contents": "Regulation of dihydrodipicolinate synthase and aspartate kinase in Bacillus subtilis. The regulation of dihydrodipicolinate synthase (EC 4.2.1.52) and aspartate kinase (EC 2.7.2.4) was studied in Bacillus subtilis 168. Starvation for lysine gave depression of one aspartate kinase isoenzyme but not of dihydrodipicolinate synthase. Strains resistant to growth inhibition by the lysine analogue thiosine exhibited constitutively derepressed synthesis of one aspartate kinase isoenzyme but had normal levels of dihydrodipicolinate synthase. The data provide strong evidence that lysine is not the signal for derepression of dihydrodipicolinate synthase. Nevertheless, dihydrodipicolinate synthase specific activity increased during sporulation, and it is suggested that this increase may result, in part, from resistance to proteolysis of that enzyme."} {"id": "PMID:163820", "title": "Coenzyme interaction with horse liver alcohol dehydrogenase. Evidence for allosteric coenzyme binding sites from thermodynamic equilibrium studies.", "content": "The techniques of fluorescence enhancement, fluorescence quenching, fluorescence polarization, and equilibrium dialysis are utilized to study the binding properties of coenzyme to horse liver alcohol dehydrogenase. Polarization of fluorescence and equilibrium dialysis show that NADH binds to alcohol dehydrogenase with a stoichiometry of 6 mol per mol of enzyme, in contrast to the value of 2 determined from fluorescence enhancement measurements. NAD+ also binds with a stoichiometry of six as was determined by equilibrium dialysis. The two NADH sites which bind coenzyme more tightly and which are revealed by fluorescence enhancement measurements are designated the catalytic sites. Binding of coenzyme to the four ancillary sites does not alter the quantum yield of NADH but results in a 20% contribution to quenching of enzyme's tryptophan fluorescence. From the emission anisotropy of bound NADH of 24.0% for the additional sites and 28.1% for the catalytic sites and their relative fluorescence lifetimes at the same wavelengths of excitation and emmision, we conclude that the nicotinamide ring of NADH bound to the additional sites exhibits a freedom of motion independent of the macromolecule, while that bound to the catalytic sites is more rigidly held. Polarization of fluorescence yields negative intrinsic free energies of 9.2 and 7.5 Cal M-1 for NADH interaction with the catalytic and additional sites, respectively. Although these values are 1.3 to 2.0 Cal higher than those determined by fluorescence quenching and equilibrium dialysis, the mean Hill coefficient of 1.76 plus or minus 0.06, the titration span of 2.4 logarithmic units and coupling free energies (in magnitude and sign) are the same for all these techniques. The above difference in the intrinsic free energies are attributed largely to the different modes of interaction of excited and unexcited NADH molecules with alcohol dehydrogenase.", "contents": "Coenzyme interaction with horse liver alcohol dehydrogenase. Evidence for allosteric coenzyme binding sites from thermodynamic equilibrium studies. The techniques of fluorescence enhancement, fluorescence quenching, fluorescence polarization, and equilibrium dialysis are utilized to study the binding properties of coenzyme to horse liver alcohol dehydrogenase. Polarization of fluorescence and equilibrium dialysis show that NADH binds to alcohol dehydrogenase with a stoichiometry of 6 mol per mol of enzyme, in contrast to the value of 2 determined from fluorescence enhancement measurements. NAD+ also binds with a stoichiometry of six as was determined by equilibrium dialysis. The two NADH sites which bind coenzyme more tightly and which are revealed by fluorescence enhancement measurements are designated the catalytic sites. Binding of coenzyme to the four ancillary sites does not alter the quantum yield of NADH but results in a 20% contribution to quenching of enzyme's tryptophan fluorescence. From the emission anisotropy of bound NADH of 24.0% for the additional sites and 28.1% for the catalytic sites and their relative fluorescence lifetimes at the same wavelengths of excitation and emmision, we conclude that the nicotinamide ring of NADH bound to the additional sites exhibits a freedom of motion independent of the macromolecule, while that bound to the catalytic sites is more rigidly held. Polarization of fluorescence yields negative intrinsic free energies of 9.2 and 7.5 Cal M-1 for NADH interaction with the catalytic and additional sites, respectively. Although these values are 1.3 to 2.0 Cal higher than those determined by fluorescence quenching and equilibrium dialysis, the mean Hill coefficient of 1.76 plus or minus 0.06, the titration span of 2.4 logarithmic units and coupling free energies (in magnitude and sign) are the same for all these techniques. The above difference in the intrinsic free energies are attributed largely to the different modes of interaction of excited and unexcited NADH molecules with alcohol dehydrogenase."} {"id": "PMID:163821", "title": "A study of the cytoplasmic receptors for glucocorticoids in intestine of pre- and postweanling rats.", "content": "Glucocorticoids cause both enzymic and morphologic changes in the rat intestine during the time of weaning. To obtain information regarding the mechanism of these actions, we examined the cytoplasmic fraction of intestines from 18-day-old rats for the presence of specific glucocorticoid-binding proteins which are characteristics of target tissues. Incubation of slices of intestine with [3H]dexamethasone in a physiological medium at 2 degrees showed the presence of a cytoplasmic binding macromolecule with high specificity for steroids having glucocorticoid activity. The binding reaction was saturable (concentration of binding sites equals 0.24 pmol per mg of protein) and of high affinity (dissociation constant equals 9.3 nM). Binding was reversible on addition of nonlabeled dexamethasone (t 1/2 equals 5.2 hours), indicating that the usual assay procedure measured both corticosterone-filled and unoccupied binding sites. Sucrose density gradient centrifugation showed that the receptor-dexamethasone complex from intestinal cytosol sedimented at the same rate as that from liver (8.2 S). The receptor-dexamethasone complex was stable at 2 degrees for at least 24 hours in intestinal slices, but in isolated cytosol fractions there was considerable loss of binding even in the presence of high concentrations of [3H]dexamethasone. Furthermore, mixing experiments showed that the presence of cytosol from intestinal mucosa (but not from the muscle layers) caused a dissociation of dexamethasone from receptors of liver cytosol. This suggested the presence of some interfering factor in isolated mucosal cytosol and meant that quantitative studies had to be confined to intact slices. Although the reasons for the instability of steroid-receptor complexes in the presence of isolated intestinal cytosol are not understood, the instability is believed to be associated with homogenization and, therefore, is believed to have no physiological significance. Finally, the ontogenesis of cytoplasmic glucocorticoid receptors in intestinal slices was examined and the pattern compared with that in liver and lung. Receptor activity was present in intestine from late fetal life through adulthood, but concentrations were significantly higher during the first two postnatal weeks than at all other times. By contrast, receptor activity detected in cytosol prepared from rat lung was high around the time of birth, while that in liver rose steadily during the first postnatal week and remained at high levels. Thus specific receptors for glucocorticoids are present in the rat intestine during periods of both responsiveness and unresponsiveness. This suggests that although corticosteroids exert their effects through the cytoplasmic receptors, this early event in glucocorticoid action may not be a controlling step for changes in responsiveness during development.", "contents": "A study of the cytoplasmic receptors for glucocorticoids in intestine of pre- and postweanling rats. Glucocorticoids cause both enzymic and morphologic changes in the rat intestine during the time of weaning. To obtain information regarding the mechanism of these actions, we examined the cytoplasmic fraction of intestines from 18-day-old rats for the presence of specific glucocorticoid-binding proteins which are characteristics of target tissues. Incubation of slices of intestine with [3H]dexamethasone in a physiological medium at 2 degrees showed the presence of a cytoplasmic binding macromolecule with high specificity for steroids having glucocorticoid activity. The binding reaction was saturable (concentration of binding sites equals 0.24 pmol per mg of protein) and of high affinity (dissociation constant equals 9.3 nM). Binding was reversible on addition of nonlabeled dexamethasone (t 1/2 equals 5.2 hours), indicating that the usual assay procedure measured both corticosterone-filled and unoccupied binding sites. Sucrose density gradient centrifugation showed that the receptor-dexamethasone complex from intestinal cytosol sedimented at the same rate as that from liver (8.2 S). The receptor-dexamethasone complex was stable at 2 degrees for at least 24 hours in intestinal slices, but in isolated cytosol fractions there was considerable loss of binding even in the presence of high concentrations of [3H]dexamethasone. Furthermore, mixing experiments showed that the presence of cytosol from intestinal mucosa (but not from the muscle layers) caused a dissociation of dexamethasone from receptors of liver cytosol. This suggested the presence of some interfering factor in isolated mucosal cytosol and meant that quantitative studies had to be confined to intact slices. Although the reasons for the instability of steroid-receptor complexes in the presence of isolated intestinal cytosol are not understood, the instability is believed to be associated with homogenization and, therefore, is believed to have no physiological significance. Finally, the ontogenesis of cytoplasmic glucocorticoid receptors in intestinal slices was examined and the pattern compared with that in liver and lung. Receptor activity was present in intestine from late fetal life through adulthood, but concentrations were significantly higher during the first two postnatal weeks than at all other times. By contrast, receptor activity detected in cytosol prepared from rat lung was high around the time of birth, while that in liver rose steadily during the first postnatal week and remained at high levels. Thus specific receptors for glucocorticoids are present in the rat intestine during periods of both responsiveness and unresponsiveness. This suggests that although corticosteroids exert their effects through the cytoplasmic receptors, this early event in glucocorticoid action may not be a controlling step for changes in responsiveness during development."} {"id": "PMID:163822", "title": "Activation of transcription by guanosine 5'-diphosphate,3'-diphosphate, transfer ribonucleic acid, and novel protein from Escherichia coli.", "content": "A protein factor TFms) that is required for ppGpp to stimulate RNA synthesis has been purified from an eluate of crude ribosomes. TFms also has the capacity to stimulate RNA synthesis without ppGpp present. Under standard conditions the action TFms and ppGpp requires uncharged tRNA. TFms and ppGpp act at inhibition to promote the formation of rifampicin-resistant or polytrI)-resistant preinitiation complexes. In the presence of rifampicin or poly(rI), tRNA is no longer required. With lambdah80dlacPs DNA as template, ppGpp together with TFms stimulated gal RNA synthesis to a much greater extent than total RNA synthesis. The stimulation of both lac and gel RNA synthesis was increased in the presence of cyclic AMP receptor and cyclic AMP.", "contents": "Activation of transcription by guanosine 5'-diphosphate,3'-diphosphate, transfer ribonucleic acid, and novel protein from Escherichia coli. A protein factor TFms) that is required for ppGpp to stimulate RNA synthesis has been purified from an eluate of crude ribosomes. TFms also has the capacity to stimulate RNA synthesis without ppGpp present. Under standard conditions the action TFms and ppGpp requires uncharged tRNA. TFms and ppGpp act at inhibition to promote the formation of rifampicin-resistant or polytrI)-resistant preinitiation complexes. In the presence of rifampicin or poly(rI), tRNA is no longer required. With lambdah80dlacPs DNA as template, ppGpp together with TFms stimulated gal RNA synthesis to a much greater extent than total RNA synthesis. The stimulation of both lac and gel RNA synthesis was increased in the presence of cyclic AMP receptor and cyclic AMP."} {"id": "PMID:163823", "title": "A persistent active state of the adenylate cyclase system produced by the combined actions of isoproterenol and guanylyl imidodiphosphate in frog erythrocyte membranes.", "content": "Isoproterenol plus guanylyl imidodiphosphate (Gpp(NH)p) activate frog erythrocyte adenylate cyclase to a level much higher than the sum of the activities produced by the catecholamine and the synthetic nucleotide tested separately. Propranolol, the beta-receptor blocking agent, failed to inhibit activity when added after the enzyme system had been preincubated with both isoproterenol and Gpp(NH)p. However, if propranolol was added after only one of the two components had been added, it inhibited the effect of isoproterenol. Production of the propranolol-resistant state by treatment with isoproterenol and Gpp(NH)p did not require the presence of the productive substrate (MgATP). The activated propranolol-resistant state persisted following various treatments of the enzyme preparation including extensive washings of the membranes; considerable activity was retained even after sonication or treatment with the detergent Lubrol-PX, treatments which caused inactivation of the native enzyme. Extensive dilution of the membranes following pretreatment with isoproterenol and Gpp(NH)p did not significantly reduce to the activity of the enzyme. Readdition of isoproterenol after dilution caused some inhibition of adenylate cyclase activity, indicating apparently that the beta-receptor has not become inaccessible. In contrast, preincubation with isoproterenol alone failed to render the enzyme system refractive to propranolol, and dilution readily reduced the activity to negligibly low values. Preincubation with Gpp(NH)p alone also produced a persistent active state but the activity was much lower than that obtained throught the combined action of isoproterenol and Gpp(NH)p. The findings suggest that the hormone may be required only to facilitate the initial interaction of the enzyme with Gpp(NH)p. The differences, in this respect, between Gpp(NH)p and the more labile natural nucleotide, GTP, are discussed.", "contents": "A persistent active state of the adenylate cyclase system produced by the combined actions of isoproterenol and guanylyl imidodiphosphate in frog erythrocyte membranes. Isoproterenol plus guanylyl imidodiphosphate (Gpp(NH)p) activate frog erythrocyte adenylate cyclase to a level much higher than the sum of the activities produced by the catecholamine and the synthetic nucleotide tested separately. Propranolol, the beta-receptor blocking agent, failed to inhibit activity when added after the enzyme system had been preincubated with both isoproterenol and Gpp(NH)p. However, if propranolol was added after only one of the two components had been added, it inhibited the effect of isoproterenol. Production of the propranolol-resistant state by treatment with isoproterenol and Gpp(NH)p did not require the presence of the productive substrate (MgATP). The activated propranolol-resistant state persisted following various treatments of the enzyme preparation including extensive washings of the membranes; considerable activity was retained even after sonication or treatment with the detergent Lubrol-PX, treatments which caused inactivation of the native enzyme. Extensive dilution of the membranes following pretreatment with isoproterenol and Gpp(NH)p did not significantly reduce to the activity of the enzyme. Readdition of isoproterenol after dilution caused some inhibition of adenylate cyclase activity, indicating apparently that the beta-receptor has not become inaccessible. In contrast, preincubation with isoproterenol alone failed to render the enzyme system refractive to propranolol, and dilution readily reduced the activity to negligibly low values. Preincubation with Gpp(NH)p alone also produced a persistent active state but the activity was much lower than that obtained throught the combined action of isoproterenol and Gpp(NH)p. The findings suggest that the hormone may be required only to facilitate the initial interaction of the enzyme with Gpp(NH)p. The differences, in this respect, between Gpp(NH)p and the more labile natural nucleotide, GTP, are discussed."} {"id": "PMID:163824", "title": "Pyridoxal phosphate-dependent conformational states of glycogen phosphorylase as probed by interconverting enzymes.", "content": "The interaction between pyridoxal 5'-phosphate and the convertible serine of glycogen phosphorylase has been investigated by using: specific interconverting enzymes, phosphorylase kinase and phosphorylase phosphatase; effectors, glucose and glucose 6-phosphate; and a protein kinase and trypsin. Both phosphorylase kinase and phosphorylase phosphatase utilized the native protein while having little influence on the apoprotein. Removal of a peptide containing the critical serine residue gave phosphorylase b' from which the pyridoxal 5'-phosphate in phosphorylase has an important effect on enzymic interconversion.", "contents": "Pyridoxal phosphate-dependent conformational states of glycogen phosphorylase as probed by interconverting enzymes. The interaction between pyridoxal 5'-phosphate and the convertible serine of glycogen phosphorylase has been investigated by using: specific interconverting enzymes, phosphorylase kinase and phosphorylase phosphatase; effectors, glucose and glucose 6-phosphate; and a protein kinase and trypsin. Both phosphorylase kinase and phosphorylase phosphatase utilized the native protein while having little influence on the apoprotein. Removal of a peptide containing the critical serine residue gave phosphorylase b' from which the pyridoxal 5'-phosphate in phosphorylase has an important effect on enzymic interconversion."} {"id": "PMID:163825", "title": "The plane of cleavage in human ferrihemoglobin. I. Ultraviolet difference spectroscopy.", "content": "X-ray diffraction studies have shown that hemoglobin has two predominant interfaces in the tetramer at which dissociation to dimers could occur. These interfaces have been designed as alpha1-beta1 and alpha1-beta2. There are 2 tyrosyl residues and 1 tryptophanyl residue in the alpha1-beta2- interface but only 1 tyrosyl residue in the alpha1-beta1 interface exposed to the solvent are perturbed. The ultraviolet difference spectrum between ferrihemoglobin dissociated in 1 M NaClO4 and undissociated hemoglobin revealed two negative peaks, one at 292.5 nm and another at 285 nm. This difference spectrum is due to tyrosyl and tryptophanyl residues which reside on the plane of cleavage and were exposed to 1 M NaClO4 upon dissociation. Hence, dissociation must have occurred along the alpha1-beta2 interface to yield alpha1 beta1 dimers. The deltaF degrees value extrapolated to zero salt concentration calculated on the basis of difference spectroscopy and sedimentation velocity experiments is 8.6 plus or minus 0.7 kcal per mol at pH 7.1 (K equals 4.5 times 10-7.", "contents": "The plane of cleavage in human ferrihemoglobin. I. Ultraviolet difference spectroscopy. X-ray diffraction studies have shown that hemoglobin has two predominant interfaces in the tetramer at which dissociation to dimers could occur. These interfaces have been designed as alpha1-beta1 and alpha1-beta2. There are 2 tyrosyl residues and 1 tryptophanyl residue in the alpha1-beta2- interface but only 1 tyrosyl residue in the alpha1-beta1 interface exposed to the solvent are perturbed. The ultraviolet difference spectrum between ferrihemoglobin dissociated in 1 M NaClO4 and undissociated hemoglobin revealed two negative peaks, one at 292.5 nm and another at 285 nm. This difference spectrum is due to tyrosyl and tryptophanyl residues which reside on the plane of cleavage and were exposed to 1 M NaClO4 upon dissociation. Hence, dissociation must have occurred along the alpha1-beta2 interface to yield alpha1 beta1 dimers. The deltaF degrees value extrapolated to zero salt concentration calculated on the basis of difference spectroscopy and sedimentation velocity experiments is 8.6 plus or minus 0.7 kcal per mol at pH 7.1 (K equals 4.5 times 10-7."} {"id": "PMID:163826", "title": "Stimulation of active uptake of nucleosides and amino acids by cyclic adenosine 3' :5'-monophosphate in the yeast Schizosaccharomyces pombe.", "content": "In conditions of glucose starvation, the maximum velocity of the mediated transport of nonmetabolized and metabolized amino acids, uridine, adenosine, and sucrose across the plasma membrane is stimulated by a factor of two by the addition of 1 mM adenosine 3':5'-monophosphate to Schizosaccharomyces pombe 972h- wild strain, to the glucose-super-repressed and derepressed mutants COB5 and COB6, and to Saccharomyces cerevisiae strain IL 216-IA. The mediated uptake of 2-D-deoxyglucose and the apparently nonmediated uptake of guanosine are not stimulated by the cyclic nucleotide. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate is also efficient, whereas theophylline, guanosine 3':5'-monophosphate, 5'-AMP, ATP, and adenosine are ineffective. The cellular ATP content of glycerol-grown S. pombe COB5 is about 10 nmol per mg of protein and is not decreased by further incubation in the starvation medium. The addition of 100 mM glucose markedly enhances transport without any increase of the cellular ATP content. The addition of antimycin A or Dio-9 decreases markedly both cellular ATP content and transport. The addition of 2.5 mM glucose to antimycin A-containing medium restores both transport is not necessarily of mitochondrial origin. The uptake of 2-D-deoxyglucose is unaffected by the respiratory inhibitors. Stimulation of uptake by cyclic adenosine 3':5'-monophosphate occurs only in glucose-deprived cells. The addition of 10 mM glucose elicits the disappearance of the stimulation and prevents the 30% decrease of the cellular adenosine 3':5'-monophosphate content produced by glucose starvation. Adenosine 3':5'-'monophosphate does not enhance the steady state ATP level but requires cellular ATP produced either by endogenous respiration or, in the absence of respiration blocked by antimycin A, by further addition of 2.5 mM glucose. Stimulation of active uptake by adenosine 3':5'-monophosphate does not require protein synthesis because the addition of cycloheximide or anisomycin does not prevent the stimulation of L-leucine uptake. In the absence of respiration, Dio-9, and ATPase inhibitor, suppresses instantaneously the cellular ejection of protons as well as the uptake of uridine and amino acids. It abolishes also the adenosine 3':5'-monophosphate-stimulated transport. In the presence of antimycin A, specific mitochondrial ATPase inhibitors such as venruricidin A do not inhibit metabolite uptakes and their stimulation by adenosine 3':5'-monophosphate. These results suggest that in these conditions, the target of Dio-9 is not the mitochondrial ATPase but a plasma membrane proton-translocating function generating an electrochemical gradient required for active transport. That adenosine 3':5'-monophosphate enhances the Dio-9-sensitive proton extrusion supports the view that the cyclic nucleotide might modulate the plasma membrane ATPase.", "contents": "Stimulation of active uptake of nucleosides and amino acids by cyclic adenosine 3' :5'-monophosphate in the yeast Schizosaccharomyces pombe. In conditions of glucose starvation, the maximum velocity of the mediated transport of nonmetabolized and metabolized amino acids, uridine, adenosine, and sucrose across the plasma membrane is stimulated by a factor of two by the addition of 1 mM adenosine 3':5'-monophosphate to Schizosaccharomyces pombe 972h- wild strain, to the glucose-super-repressed and derepressed mutants COB5 and COB6, and to Saccharomyces cerevisiae strain IL 216-IA. The mediated uptake of 2-D-deoxyglucose and the apparently nonmediated uptake of guanosine are not stimulated by the cyclic nucleotide. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate is also efficient, whereas theophylline, guanosine 3':5'-monophosphate, 5'-AMP, ATP, and adenosine are ineffective. The cellular ATP content of glycerol-grown S. pombe COB5 is about 10 nmol per mg of protein and is not decreased by further incubation in the starvation medium. The addition of 100 mM glucose markedly enhances transport without any increase of the cellular ATP content. The addition of antimycin A or Dio-9 decreases markedly both cellular ATP content and transport. The addition of 2.5 mM glucose to antimycin A-containing medium restores both transport is not necessarily of mitochondrial origin. The uptake of 2-D-deoxyglucose is unaffected by the respiratory inhibitors. Stimulation of uptake by cyclic adenosine 3':5'-monophosphate occurs only in glucose-deprived cells. The addition of 10 mM glucose elicits the disappearance of the stimulation and prevents the 30% decrease of the cellular adenosine 3':5'-monophosphate content produced by glucose starvation. Adenosine 3':5'-'monophosphate does not enhance the steady state ATP level but requires cellular ATP produced either by endogenous respiration or, in the absence of respiration blocked by antimycin A, by further addition of 2.5 mM glucose. Stimulation of active uptake by adenosine 3':5'-monophosphate does not require protein synthesis because the addition of cycloheximide or anisomycin does not prevent the stimulation of L-leucine uptake. In the absence of respiration, Dio-9, and ATPase inhibitor, suppresses instantaneously the cellular ejection of protons as well as the uptake of uridine and amino acids. It abolishes also the adenosine 3':5'-monophosphate-stimulated transport. In the presence of antimycin A, specific mitochondrial ATPase inhibitors such as venruricidin A do not inhibit metabolite uptakes and their stimulation by adenosine 3':5'-monophosphate. These results suggest that in these conditions, the target of Dio-9 is not the mitochondrial ATPase but a plasma membrane proton-translocating function generating an electrochemical gradient required for active transport. That adenosine 3':5'-monophosphate enhances the Dio-9-sensitive proton extrusion supports the view that the cyclic nucleotide might modulate the plasma membrane ATPase."} {"id": "PMID:163827", "title": "The mechanism of stabilization of the structure of nuclease-T by binding of ligands.", "content": "The rate of unfolding of Nuclease-T at pH 8,20 degrees was determined as a function of concentration of the ligands deoxythymidine 3',5'-diphosphate (pdTp) and Ca2+ on the basis of the rate of exchange between free fragment, Nuclease-T(50-149) and labeled fragment, Nuclease-T-(50-149) incorporated in the structure of nuclease-T (Taniuchi, H. (1973) J. Biol. Chem. 248, 5164-5174). The rate constant of unfolding of unliganded Nuclease-T' was 4.6 times 10-4s-1. Those of Nuclease-T' bound with pdTp, with Ca2+, and with both pdtp and Ca2+ were 9.0 times 10-5, 1.6 times 10-4, and 2.2 times 10-5s-1, respectively. The association constants of pdTp and Ca2+ with Nuclease-T' were found to be 1.0 times 10-4 and 2.0 times 10-2 m-1, respectively. Those of pdTp with Nuclease-T' plus Ca2+ and of Ca2+ with Nuclease-T' plus pdTp were 4 times 10-5 and 1.4 times 10-4M-1, respectively. The calculation of free energy change on the basis of the association constants shows that the magnitude of negative free energy change involved in the binding of either of the two ligands increases by approximately 2 kcal when the other ligand is already bound. There is a correlation between the free energy change and the specifically coupled with the cooperative interacions operating throught the three-dimensional structure resulting in strengthening of the interactions throughtout the structure, including those with the ligands, without a large change in conformation.", "contents": "The mechanism of stabilization of the structure of nuclease-T by binding of ligands. The rate of unfolding of Nuclease-T at pH 8,20 degrees was determined as a function of concentration of the ligands deoxythymidine 3',5'-diphosphate (pdTp) and Ca2+ on the basis of the rate of exchange between free fragment, Nuclease-T(50-149) and labeled fragment, Nuclease-T-(50-149) incorporated in the structure of nuclease-T (Taniuchi, H. (1973) J. Biol. Chem. 248, 5164-5174). The rate constant of unfolding of unliganded Nuclease-T' was 4.6 times 10-4s-1. Those of Nuclease-T' bound with pdTp, with Ca2+, and with both pdtp and Ca2+ were 9.0 times 10-5, 1.6 times 10-4, and 2.2 times 10-5s-1, respectively. The association constants of pdTp and Ca2+ with Nuclease-T' were found to be 1.0 times 10-4 and 2.0 times 10-2 m-1, respectively. Those of pdTp with Nuclease-T' plus Ca2+ and of Ca2+ with Nuclease-T' plus pdTp were 4 times 10-5 and 1.4 times 10-4M-1, respectively. The calculation of free energy change on the basis of the association constants shows that the magnitude of negative free energy change involved in the binding of either of the two ligands increases by approximately 2 kcal when the other ligand is already bound. There is a correlation between the free energy change and the specifically coupled with the cooperative interacions operating throught the three-dimensional structure resulting in strengthening of the interactions throughtout the structure, including those with the ligands, without a large change in conformation."} {"id": "PMID:163828", "title": "The generation of O2-by the interaction of the hemolytic agent, phenylhydrazine, with human hemoglobin.", "content": "Phenylhydrazine reacts with adult oxy- or methemoglobin in the presence of molecular oxygen to generate O2-. The mechanism of the reaction apparently differs in each case. The generation of O2- is monitored by following the reduction of ferricytochrome c or the oxidation of epinephrine.", "contents": "The generation of O2-by the interaction of the hemolytic agent, phenylhydrazine, with human hemoglobin. Phenylhydrazine reacts with adult oxy- or methemoglobin in the presence of molecular oxygen to generate O2-. The mechanism of the reaction apparently differs in each case. The generation of O2- is monitored by following the reduction of ferricytochrome c or the oxidation of epinephrine."} {"id": "PMID:163829", "title": "Hapten-sandwich labeling. II. Immunospecific attachment of cell surface markers suitable for scanning electron microscopy.", "content": "A hapten-sandwich procedure has been used for immunospecific labeling of cell surface antigens with markers visible by scanning electron microscopy. Antihapten antibody was used to link hapten-modified tobacco mosaic virus, bushy stunt virus, or hemocyanin to hapten-modified human erythrocytes. The antihapten antibody bridge was also used to link the hapten-virus marker to hapten-modified antibodies against mammary tumor virus on mouse mammary tumor cells, or against immunoglobulin receptors on mouse splenic lymphocytes. In all cases, labeling was highly specific. With this technique, it is possible to (a) compare morphological features of cells bearing differing cell surface antigens, and (b) examine the arrangement of specific antigenic sites on a cell surface or their distribution relative to membrane structures such as microvilli.", "contents": "Hapten-sandwich labeling. II. Immunospecific attachment of cell surface markers suitable for scanning electron microscopy. A hapten-sandwich procedure has been used for immunospecific labeling of cell surface antigens with markers visible by scanning electron microscopy. Antihapten antibody was used to link hapten-modified tobacco mosaic virus, bushy stunt virus, or hemocyanin to hapten-modified human erythrocytes. The antihapten antibody bridge was also used to link the hapten-virus marker to hapten-modified antibodies against mammary tumor virus on mouse mammary tumor cells, or against immunoglobulin receptors on mouse splenic lymphocytes. In all cases, labeling was highly specific. With this technique, it is possible to (a) compare morphological features of cells bearing differing cell surface antigens, and (b) examine the arrangement of specific antigenic sites on a cell surface or their distribution relative to membrane structures such as microvilli."} {"id": "PMID:163830", "title": "Further characterization of embryonic tendon fibroblasts and the use of immunoferritin techniques to study collagen biosynthesis.", "content": "Morphological studies were carried out on fibroblasts from chick embryo tendons, cells which have been used in a number of recent studies on collagen biosynthesis. The cells were relatively rich in endoplasmic reticulum and contained a well-developed Golgi complex comprised of small vesicles, stacked membranes, and large vacuoles. Techniques were then devised for preparing cell fragments which were penetrated by ferritin-antibody conjuates but which retained the essential morphological features of the cells. Finally, the new procedures were employed to develop further information as to how collagen is synthesized. As reported elsewhere, preliminary studies with ferritin-labeled antibodies showed that prolyl hydroxylase was found in the endoplasmic reticulum of freshly isolated fibroblasts and that procollagen is found in both the cisternae of the endoplasmic reticulum and the large Golgi vacuoles. In the experiments described here, the cells were manipulated so that amino acids continued to be incorporated into polypeptide chains but assembly of the molecule was not completed because hydroxylation of prolyl and lysyl residues was prevented. The results indicated that these manipulations produced no change in the distribution of prolyl hydroxylase. Examination of the cells with ferritin conjugated to antibodies which reacted with protocollagen, the unhydroxylated form of procollagen, demonstrated that protocollagen was retained in the cisternae of the endoplasmic reticulum during inhibition of the prolyl and lysyl hydroxylases. Assays for prolyl hydroxylase with an immunologic technique demonstrated that although the enzyme is found within the endoplasmic reticulum, it is not secreted along with procollagen. The observations provided further evidence for a special role for prolyl hydroxylase in the control of collagen biosynthesis.", "contents": "Further characterization of embryonic tendon fibroblasts and the use of immunoferritin techniques to study collagen biosynthesis. Morphological studies were carried out on fibroblasts from chick embryo tendons, cells which have been used in a number of recent studies on collagen biosynthesis. The cells were relatively rich in endoplasmic reticulum and contained a well-developed Golgi complex comprised of small vesicles, stacked membranes, and large vacuoles. Techniques were then devised for preparing cell fragments which were penetrated by ferritin-antibody conjuates but which retained the essential morphological features of the cells. Finally, the new procedures were employed to develop further information as to how collagen is synthesized. As reported elsewhere, preliminary studies with ferritin-labeled antibodies showed that prolyl hydroxylase was found in the endoplasmic reticulum of freshly isolated fibroblasts and that procollagen is found in both the cisternae of the endoplasmic reticulum and the large Golgi vacuoles. In the experiments described here, the cells were manipulated so that amino acids continued to be incorporated into polypeptide chains but assembly of the molecule was not completed because hydroxylation of prolyl and lysyl residues was prevented. The results indicated that these manipulations produced no change in the distribution of prolyl hydroxylase. Examination of the cells with ferritin conjugated to antibodies which reacted with protocollagen, the unhydroxylated form of procollagen, demonstrated that protocollagen was retained in the cisternae of the endoplasmic reticulum during inhibition of the prolyl and lysyl hydroxylases. Assays for prolyl hydroxylase with an immunologic technique demonstrated that although the enzyme is found within the endoplasmic reticulum, it is not secreted along with procollagen. The observations provided further evidence for a special role for prolyl hydroxylase in the control of collagen biosynthesis."} {"id": "PMID:163831", "title": "Detection by means of cell fusion of macromolecular synthesis involved in the reconstruction of the nuclear envelope in mitosis.", "content": "Using the cultured Chinese hamster cell line Don, G1 or S or a mixture of late-S/G2 cells were prepared by release from metaphase arrest. Metaphase (M) cells were also obtained by mitotic arrest of log-phase cultures with Colcemid and held in metaphase; such M cells remained untreated with any other compound and were termed standard M cells. When interphase (I) cells were fused at pH 8.0 and 37 degrees C with standard cells in the presence of Colcemid by means of UV-inactivated Sendai virus, binucleate interphase-metaphase (I-M) cells were obtained. In a given I-M cell there occurred within 30 min after fusion either prophasing of the I nucleus or formation of a nuclear envelope (NE) around the chromosomes. About 20% of early G1 cells, 35% of cells at the G1/S boundary, 50% of S cells, and 70% of late S/G2 cells could induce NE formation. If, before fusion, cycloheximide (CHE), an inhibitor of protein synthesis, was present during release from M arrest, the cells entered G1 but not S. About 20% of such early G1 cells, like the untreated early G1 cells, had the capacity to induce NE formation during subsequent fusion. If the cells were blocked in S with 5 mM thymidine (TdR), At least 80% of these cells could induce NE formation during subsequent fusion, but in the presence of both TdR and CHE only 35% could do so. It appeared, therefore, that protein synthesis in interphase was required for NE formation. Experiments with actinomycin D indicated that RNA synthesis was also necessary for acquisition of NE-inducing capacity. About 35% of G1 cells from confluent monolayers had the NE-inducing capacity, but prolonged exposure to CHE reduced their number to 8% . Removal of CHE restored the ability while the cells still remained in G1. This result indicated that continuing protein synthesis in the G1 cell was needed for NE formation subsequent to fusion. The fact that macromolecular synthesis must occur in the I cell before fusion if NE formation was to occur in the fused I-M cell lends further support to evidence adduced earlier that this phenomenon is a normal mitotic event. Prophasing of the I nucleus in I-M cells did not appear to be dependent on macromolecular synthesis in the I cell; earlier results from this laboratory showed, however, that protein synthesis in the prior G2 period of the M cell of the I-M pair was required for prophasing.", "contents": "Detection by means of cell fusion of macromolecular synthesis involved in the reconstruction of the nuclear envelope in mitosis. Using the cultured Chinese hamster cell line Don, G1 or S or a mixture of late-S/G2 cells were prepared by release from metaphase arrest. Metaphase (M) cells were also obtained by mitotic arrest of log-phase cultures with Colcemid and held in metaphase; such M cells remained untreated with any other compound and were termed standard M cells. When interphase (I) cells were fused at pH 8.0 and 37 degrees C with standard cells in the presence of Colcemid by means of UV-inactivated Sendai virus, binucleate interphase-metaphase (I-M) cells were obtained. In a given I-M cell there occurred within 30 min after fusion either prophasing of the I nucleus or formation of a nuclear envelope (NE) around the chromosomes. About 20% of early G1 cells, 35% of cells at the G1/S boundary, 50% of S cells, and 70% of late S/G2 cells could induce NE formation. If, before fusion, cycloheximide (CHE), an inhibitor of protein synthesis, was present during release from M arrest, the cells entered G1 but not S. About 20% of such early G1 cells, like the untreated early G1 cells, had the capacity to induce NE formation during subsequent fusion. If the cells were blocked in S with 5 mM thymidine (TdR), At least 80% of these cells could induce NE formation during subsequent fusion, but in the presence of both TdR and CHE only 35% could do so. It appeared, therefore, that protein synthesis in interphase was required for NE formation. Experiments with actinomycin D indicated that RNA synthesis was also necessary for acquisition of NE-inducing capacity. About 35% of G1 cells from confluent monolayers had the NE-inducing capacity, but prolonged exposure to CHE reduced their number to 8% . Removal of CHE restored the ability while the cells still remained in G1. This result indicated that continuing protein synthesis in the G1 cell was needed for NE formation subsequent to fusion. The fact that macromolecular synthesis must occur in the I cell before fusion if NE formation was to occur in the fused I-M cell lends further support to evidence adduced earlier that this phenomenon is a normal mitotic event. Prophasing of the I nucleus in I-M cells did not appear to be dependent on macromolecular synthesis in the I cell; earlier results from this laboratory showed, however, that protein synthesis in the prior G2 period of the M cell of the I-M pair was required for prophasing."} {"id": "PMID:163832", "title": "Cell surface changes and Rous sarcoma virus gene expression in synchronized cells.", "content": "We have investigated whether cell surface changes associated with growth control and malignant transformation are linked to the cell cycle. Chicken embryo cells synchronized by double thymidine block were examined for cell-cycle-dependent alterations in membrane function (measured by transport of 2-deoxyglucose, uridine, thymidine, and mannitol), in cell surface morphology (examined by scanning electron microscopy), and in the ability of tumor virus gene expression to induce a transformation-specific change in membrane function. We reach the following conclusions: (a) The high rate of 2-deoxyglucose transport seen in transformed cells and the low rates of 2-deoxyglucose and uridine transport characteristic of density-inhibited cells do not occur in normal growing cells as they traverse the cell cycle. (b) Although there are cell cycle-dependent changes in surface morphology, they are not reflected in corresponding changes in membrane function. (c) Tumor virus gene expression can alter cell membrane function at any stage in the cell cycle and without progression through the cell cycle.", "contents": "Cell surface changes and Rous sarcoma virus gene expression in synchronized cells. We have investigated whether cell surface changes associated with growth control and malignant transformation are linked to the cell cycle. Chicken embryo cells synchronized by double thymidine block were examined for cell-cycle-dependent alterations in membrane function (measured by transport of 2-deoxyglucose, uridine, thymidine, and mannitol), in cell surface morphology (examined by scanning electron microscopy), and in the ability of tumor virus gene expression to induce a transformation-specific change in membrane function. We reach the following conclusions: (a) The high rate of 2-deoxyglucose transport seen in transformed cells and the low rates of 2-deoxyglucose and uridine transport characteristic of density-inhibited cells do not occur in normal growing cells as they traverse the cell cycle. (b) Although there are cell cycle-dependent changes in surface morphology, they are not reflected in corresponding changes in membrane function. (c) Tumor virus gene expression can alter cell membrane function at any stage in the cell cycle and without progression through the cell cycle."} {"id": "PMID:163833", "title": "Externally disposed plasma membrane proteins. I. Enzymatic iodination of mouse L cells.", "content": "The enzymatic iodination technique has been utilized in a study of the externally disposed membrane proteins of the mouse L cell. Iodination of cells in suspension results in lactoperoxidase-specific iodide incorporation with no loss of cell viability under the conditions employed, less than 3% lipid labeling, and more than 90% of the labeled species identifiable as monoiodotyrosine. 90% of the incorporated label is localized to the cell surface by electron microscope autoradiography, with 5-10% in the centrosphere region and postulated to represent pinocytic vesicles. Sodium dodecylsulfate-polyacrylamide gels of solubilized L-cell proteins reveals five to six labeled peaks ranging from 50,000 to 200,000 daltons. Increased resolution by use of gradient slab gels reveals 15-20 radioactive bands. Over 60% of the label resides in approximately nine polypeptides of 80,000 to 150,000 daltons. Various controls indicate that the labeling pattern reflects endogenous membrane proteins, not serum components. The incorporated 125-I, cholesterol, and one plasma membrane enzyme marker, alkaline phosphodiesterase I, are purified in parallel when plasma membranes are isolated from intact, iodinated L cells. The labeled components present in a plasma membrane-rich fraction from iodinated cells are identical to those of the total cell, with a 10- to 20-fold enrichment in specific activity of each radioactive peak in the membrane.", "contents": "Externally disposed plasma membrane proteins. I. Enzymatic iodination of mouse L cells. The enzymatic iodination technique has been utilized in a study of the externally disposed membrane proteins of the mouse L cell. Iodination of cells in suspension results in lactoperoxidase-specific iodide incorporation with no loss of cell viability under the conditions employed, less than 3% lipid labeling, and more than 90% of the labeled species identifiable as monoiodotyrosine. 90% of the incorporated label is localized to the cell surface by electron microscope autoradiography, with 5-10% in the centrosphere region and postulated to represent pinocytic vesicles. Sodium dodecylsulfate-polyacrylamide gels of solubilized L-cell proteins reveals five to six labeled peaks ranging from 50,000 to 200,000 daltons. Increased resolution by use of gradient slab gels reveals 15-20 radioactive bands. Over 60% of the label resides in approximately nine polypeptides of 80,000 to 150,000 daltons. Various controls indicate that the labeling pattern reflects endogenous membrane proteins, not serum components. The incorporated 125-I, cholesterol, and one plasma membrane enzyme marker, alkaline phosphodiesterase I, are purified in parallel when plasma membranes are isolated from intact, iodinated L cells. The labeled components present in a plasma membrane-rich fraction from iodinated cells are identical to those of the total cell, with a 10- to 20-fold enrichment in specific activity of each radioactive peak in the membrane."} {"id": "PMID:163834", "title": "Externally disposed plasma membrane proteins. II. Metabolic fate of iodinated polypeptides of mouse L cells.", "content": "The fate of the L-cell plasma membrane proteins labeled by enzymatic iodination was studied. The disappearance of label from growing cells exhibits a biphasic behavior, with 5-20% lost rapidly (t1/2 similar to 2 h) and 80-90% lost relatively slowly (t1/2 similar to 25-33 h). The loss is temperature dependent and serum independent, and is accompanied by the appearance of 51% (125-I)monoiodotyrosine (MIT) in the medium by 47 h. A variable amount (1-14%) of acid-insoluble label can be recovered in the medium over 47 h. Sodium dodecyl sulfate (SDS)-polyacrylamide gel labeling patterns from cells cultured up to 48 h after iodination reveal no change in the relative distribution of radioactivity, indicating similar rates of degradation for most of the labeled membrane proteins. The fate of the labeled membrane proteins was studied at various times after phagocytosis of nondigestible polystyrene particles. Iodinated L cells phagocytose sufficient 1.1 mum latex beads in 60 min to interiorize 15-30% of the total cell surface area. Electron microscope autoradiography confirmed that labeled membrane is internalized during phagocytosis. The latex-containing phagocytic vacuoles are isolated by flotation in a discontinuous sucrose gradient. 15-30% of the total incorporated label and a comparable percentage of alkaline phosphodiesterase I activity (PDase, a plasma membrane enzyme marker) are recovered in the phagocytic vacuole fraction. Lysosomal enzyme activities are found in the latex vacuole fraction, indicating formation of phagolysosomes. SDS gel analyses reveal that all of the radioactive proteins initially present on the intact cell's surface are interiorized to the same relative extent. Incorporated label and PDase activity disappear much more rapidly from the phagolysosomes than from the whole cell. In the phagolysosomal compartment, greater than 70% of the TCA-precipitable labeled proteins and all of the PDase activity are lost rapidly (t1/2 equals 1-2 h) but similar 30% of the labeled proteins in this compartment are degraded with a 17-20 h half-life. The slowly degraded label is due to specific long-lived polypeptides, of 85,000 and 8,000-15,000 daltons, which remain in the phagolysosomal membrane up to 40 h after phagocytosis.", "contents": "Externally disposed plasma membrane proteins. II. Metabolic fate of iodinated polypeptides of mouse L cells. The fate of the L-cell plasma membrane proteins labeled by enzymatic iodination was studied. The disappearance of label from growing cells exhibits a biphasic behavior, with 5-20% lost rapidly (t1/2 similar to 2 h) and 80-90% lost relatively slowly (t1/2 similar to 25-33 h). The loss is temperature dependent and serum independent, and is accompanied by the appearance of 51% (125-I)monoiodotyrosine (MIT) in the medium by 47 h. A variable amount (1-14%) of acid-insoluble label can be recovered in the medium over 47 h. Sodium dodecyl sulfate (SDS)-polyacrylamide gel labeling patterns from cells cultured up to 48 h after iodination reveal no change in the relative distribution of radioactivity, indicating similar rates of degradation for most of the labeled membrane proteins. The fate of the labeled membrane proteins was studied at various times after phagocytosis of nondigestible polystyrene particles. Iodinated L cells phagocytose sufficient 1.1 mum latex beads in 60 min to interiorize 15-30% of the total cell surface area. Electron microscope autoradiography confirmed that labeled membrane is internalized during phagocytosis. The latex-containing phagocytic vacuoles are isolated by flotation in a discontinuous sucrose gradient. 15-30% of the total incorporated label and a comparable percentage of alkaline phosphodiesterase I activity (PDase, a plasma membrane enzyme marker) are recovered in the phagocytic vacuole fraction. Lysosomal enzyme activities are found in the latex vacuole fraction, indicating formation of phagolysosomes. SDS gel analyses reveal that all of the radioactive proteins initially present on the intact cell's surface are interiorized to the same relative extent. Incorporated label and PDase activity disappear much more rapidly from the phagolysosomes than from the whole cell. In the phagolysosomal compartment, greater than 70% of the TCA-precipitable labeled proteins and all of the PDase activity are lost rapidly (t1/2 equals 1-2 h) but similar 30% of the labeled proteins in this compartment are degraded with a 17-20 h half-life. The slowly degraded label is due to specific long-lived polypeptides, of 85,000 and 8,000-15,000 daltons, which remain in the phagolysosomal membrane up to 40 h after phagocytosis."} {"id": "PMID:163837", "title": "Gas-liquid chromatography of carotenoids and other terpenoids.", "content": "The retention behaviour of over seventy terpenoids on three silicone polymer liquid phases under both isothermal and temperature-programmed conditions is reported. Terpenoids with conjugated unsaturation (e.g., carotenoids) were hydrogenated prior to analysis in order to prevent thermal decomposition. Analyses of the acetates and TMS ethers of both the natural hydroxycarotenoids and their perhydroderivatives are also reported. In addition, a system is described for the routine analysis of terpenols, including those whose pyrophosphates are intermediates in sterol and carotenoid biosynthesis.", "contents": "Gas-liquid chromatography of carotenoids and other terpenoids. The retention behaviour of over seventy terpenoids on three silicone polymer liquid phases under both isothermal and temperature-programmed conditions is reported. Terpenoids with conjugated unsaturation (e.g., carotenoids) were hydrogenated prior to analysis in order to prevent thermal decomposition. Analyses of the acetates and TMS ethers of both the natural hydroxycarotenoids and their perhydroderivatives are also reported. In addition, a system is described for the routine analysis of terpenols, including those whose pyrophosphates are intermediates in sterol and carotenoid biosynthesis."} {"id": "PMID:163840", "title": "Blood testosterone values in patients with congenital virilizing adrenal hyperplasia.", "content": "To evaluate the usefulness of blood testosterone (T) in monitoring the effects of therapy in congenital virilizing adrenal hyperplasia due to 21- or 11- hydroxylation defect (CVAH), T levels were measured on 45 occasions in 13 patients with CVAH; 32 urinary 17-ketosteroid levels and 31 preganetriol values were available for comparison. Bone age levels, growth data, and medication are listed to help assess the clinical state of the patient at the time of each T determination. Blood T values were above normal for age and sex in untreated patients with CVAH and declined with glucocorticoid suppression. A blood T value of 20 ng/100 ml appeared to distinguish between well-controlled cases and those with inadequate steroid suppression. Serial measurement of blood T in girls and in prepubertal boys with CVAH provides assistance in evaluating chemical control of the disease, particularly when accurate 24-h urine collections cannot be obtained for 17-ketosteroid and pregnanetriol assessments.", "contents": "Blood testosterone values in patients with congenital virilizing adrenal hyperplasia. To evaluate the usefulness of blood testosterone (T) in monitoring the effects of therapy in congenital virilizing adrenal hyperplasia due to 21- or 11- hydroxylation defect (CVAH), T levels were measured on 45 occasions in 13 patients with CVAH; 32 urinary 17-ketosteroid levels and 31 preganetriol values were available for comparison. Bone age levels, growth data, and medication are listed to help assess the clinical state of the patient at the time of each T determination. Blood T values were above normal for age and sex in untreated patients with CVAH and declined with glucocorticoid suppression. A blood T value of 20 ng/100 ml appeared to distinguish between well-controlled cases and those with inadequate steroid suppression. Serial measurement of blood T in girls and in prepubertal boys with CVAH provides assistance in evaluating chemical control of the disease, particularly when accurate 24-h urine collections cannot be obtained for 17-ketosteroid and pregnanetriol assessments."} {"id": "PMID:163841", "title": "Interaction of delta-5-androstene-3beta, 17beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue.", "content": "Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.", "contents": "Interaction of delta-5-androstene-3beta, 17beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue. Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells."} {"id": "PMID:163842", "title": "Regulation of human chorionic gonadotropin (hCG) secretion by serum and dibutyryl cyclic AMP in malignant trophoblast cells in vitro.", "content": "Human chorionic gonadotropin (hCG) secretion was studied in human malignant trophoblast cells (Jar line) in continuous culture. Radioimmunoassayable hCG in the cells and in the daily culture fluid was increased for at least 3 days by 10% newborn calf serum and by 1 mN N-6, 0-2'-dibutyryl cyclic adenosine 3', 5'-monophosphoric acid (dbcAMP) plus 1 mM theorphylline. Incubation of the cells in the presence of serum, dbcAMP and theorphylline resulted in additive stimulation of hCG secretion after 1 day. After 2 or 3 days, a supra-additive stimulation was observed, which was prevented by Actinomycin D. When cells were preincubated for 2 days in the absence of serum but with dbcAMP plus theorphylline, subsequent addition of serum resulted in supra-additive stimulation of hCG secretion within a single day; the continued presence of dbcAMP plus theophylline was not necessary for this stimulation by serum. These findings suggested that dbcAMP activates a slow process requiring RNA synthesis, resulting in increased hCG secretion. Serum appears to protect the hCG synthesizing system from degradation.", "contents": "Regulation of human chorionic gonadotropin (hCG) secretion by serum and dibutyryl cyclic AMP in malignant trophoblast cells in vitro. Human chorionic gonadotropin (hCG) secretion was studied in human malignant trophoblast cells (Jar line) in continuous culture. Radioimmunoassayable hCG in the cells and in the daily culture fluid was increased for at least 3 days by 10% newborn calf serum and by 1 mN N-6, 0-2'-dibutyryl cyclic adenosine 3', 5'-monophosphoric acid (dbcAMP) plus 1 mM theorphylline. Incubation of the cells in the presence of serum, dbcAMP and theorphylline resulted in additive stimulation of hCG secretion after 1 day. After 2 or 3 days, a supra-additive stimulation was observed, which was prevented by Actinomycin D. When cells were preincubated for 2 days in the absence of serum but with dbcAMP plus theorphylline, subsequent addition of serum resulted in supra-additive stimulation of hCG secretion within a single day; the continued presence of dbcAMP plus theophylline was not necessary for this stimulation by serum. These findings suggested that dbcAMP activates a slow process requiring RNA synthesis, resulting in increased hCG secretion. Serum appears to protect the hCG synthesizing system from degradation."} {"id": "PMID:163843", "title": "Immunochemical heterogeneity of calcitonin in plasma.", "content": "Calcitonin was measured in the plasma of 13 patients with medullary throid carcinoma and one patient with a calcitonin-producing islet cell carcinoma of the pancreas. The hormone was measured by the simultaneous application of two calcitonin antisera which had differing specificity. Calcitonin measurements were also made of gel filtration (Bio Gel P30) fractions of plasma samples. Although the two antisera were of comparable sensitivity for the measurement of human calcitonin standards, they reacted differently with the calcitonin in the plasma samples. One antiserum (LD-1) gave consistently higher estimations of hormone concentration in the plasma of patients with medullary thyroid carcinoma than the other (LD-26). By contrast, the concentration of calcitonin from the islet cell carcinoma of the pancreas was higher in the LD-26 assay. Multiple gel filtration peaks of immunoreactive calcitonin activity were present in both thyroidal and nonthyroidal calcitonin. Furthermore, the two different antisera identified differing immunochemical peaks of calcitonin activity for agiven plasma sample. These findings demonstrate the presence of immunochemical heterogeneity in plasma calcitonin and suggest the presence of immunological differences between thyroidal and nonthyroidal calcitonin.", "contents": "Immunochemical heterogeneity of calcitonin in plasma. Calcitonin was measured in the plasma of 13 patients with medullary throid carcinoma and one patient with a calcitonin-producing islet cell carcinoma of the pancreas. The hormone was measured by the simultaneous application of two calcitonin antisera which had differing specificity. Calcitonin measurements were also made of gel filtration (Bio Gel P30) fractions of plasma samples. Although the two antisera were of comparable sensitivity for the measurement of human calcitonin standards, they reacted differently with the calcitonin in the plasma samples. One antiserum (LD-1) gave consistently higher estimations of hormone concentration in the plasma of patients with medullary thyroid carcinoma than the other (LD-26). By contrast, the concentration of calcitonin from the islet cell carcinoma of the pancreas was higher in the LD-26 assay. Multiple gel filtration peaks of immunoreactive calcitonin activity were present in both thyroidal and nonthyroidal calcitonin. Furthermore, the two different antisera identified differing immunochemical peaks of calcitonin activity for agiven plasma sample. These findings demonstrate the presence of immunochemical heterogeneity in plasma calcitonin and suggest the presence of immunological differences between thyroidal and nonthyroidal calcitonin."} {"id": "PMID:163844", "title": "Effects of glucocorticoids on pituitary hormonal responses to hypoglycemia. Inhibition of prolactin release.", "content": "The characteristics of pituitary hormonal responses to insulin-induced hypoglycemia were investigated in 16 normal men. In all subjects, levels of blood sugar fell below 35 mg/100 ml. A statistically significant increase in mean plasma levels of prolactin, ACTH, cortisol and growth hormone was observed. Prolactin levels increased in all subjects but one; individual peak values were 1.4 minus 8.4 times greater than base levels. The kinetics of prolactin, GH and ACTH responses were similar; in particular, the onset of release (25 min) of prolactin, GH and ACTH was similar. After dexamethasone administration, insulin tolerance tests wererepeated in a number of subjects using adequate amounts of insulin to achieve hypoglycemia equivalent to that obtained in the control experiments. The administration of 1 mg of dexamethasone the evening before the test suppressed basal levels of ACTH and cortisol and the ACTH-but not the cortisol-response to hypoglycemia. Both basal levels of prolactin and prolactin response to hypoglycemia were significantly lowered but growth hormone response was not modified by administration of 1 mg of dexamethasone. The administration of larger doses of dexamethasone (1 mg every 6 h for 2 days) almost completely suppressed basal levels of ACTH, cortisol and prolactin, as well as the hypoglycemia-induced release of these hormones. In contrast, the growth hormone response to hypoglycemia was only partially inhibited. These findings demonstrate that both basal secretion and hypoglycemia-induced release of prolactin, ACTH, cortisol and growth hormone are suppressible by glucocorticoids.", "contents": "Effects of glucocorticoids on pituitary hormonal responses to hypoglycemia. Inhibition of prolactin release. The characteristics of pituitary hormonal responses to insulin-induced hypoglycemia were investigated in 16 normal men. In all subjects, levels of blood sugar fell below 35 mg/100 ml. A statistically significant increase in mean plasma levels of prolactin, ACTH, cortisol and growth hormone was observed. Prolactin levels increased in all subjects but one; individual peak values were 1.4 minus 8.4 times greater than base levels. The kinetics of prolactin, GH and ACTH responses were similar; in particular, the onset of release (25 min) of prolactin, GH and ACTH was similar. After dexamethasone administration, insulin tolerance tests wererepeated in a number of subjects using adequate amounts of insulin to achieve hypoglycemia equivalent to that obtained in the control experiments. The administration of 1 mg of dexamethasone the evening before the test suppressed basal levels of ACTH and cortisol and the ACTH-but not the cortisol-response to hypoglycemia. Both basal levels of prolactin and prolactin response to hypoglycemia were significantly lowered but growth hormone response was not modified by administration of 1 mg of dexamethasone. The administration of larger doses of dexamethasone (1 mg every 6 h for 2 days) almost completely suppressed basal levels of ACTH, cortisol and prolactin, as well as the hypoglycemia-induced release of these hormones. In contrast, the growth hormone response to hypoglycemia was only partially inhibited. These findings demonstrate that both basal secretion and hypoglycemia-induced release of prolactin, ACTH, cortisol and growth hormone are suppressible by glucocorticoids."} {"id": "PMID:163845", "title": "Free cortisol index: a rapid and simple estimation of free cortisol in human plasma.", "content": "A rapid and simple method for the estimation of free (nonprotein-bound) cortisol in human plasma is described. Total plasma cortisol (F) was determined by a competitive protein binding assay. An estimate of the saturation of Corticosteroid Binding Globulin was obtained by the use of \"charcoal cortisol uptake\" (CFU). \"Charcoal cortisol uptake ratio\" (CFUR) was defined as the ratio of the CFU of the unknown plasma to that of a reference serum pool. Free cortisol index (FFI) was calculated as (total plasma F) times (CFUR). Percent free cortisol and free cortisol concentration (FF) was determined by equilibrium dialysis at 37 C. 169 plasma samples with an F range of 0.8-61.2 mug/100 ml from 18 normal, 10 ACTH-stimulated, 17 estrogen-treated and 12 pregnant subjects were analyzed. A highly significant correlation between FFI and FF was found (r = 0.952). Inter-assay coefficients of variation were 7% for total plasma F and 3.5% for CFU. The method allows the rapid processing of large numbers of samples and can be performed on 0.2 ml of plasma.", "contents": "Free cortisol index: a rapid and simple estimation of free cortisol in human plasma. A rapid and simple method for the estimation of free (nonprotein-bound) cortisol in human plasma is described. Total plasma cortisol (F) was determined by a competitive protein binding assay. An estimate of the saturation of Corticosteroid Binding Globulin was obtained by the use of \"charcoal cortisol uptake\" (CFU). \"Charcoal cortisol uptake ratio\" (CFUR) was defined as the ratio of the CFU of the unknown plasma to that of a reference serum pool. Free cortisol index (FFI) was calculated as (total plasma F) times (CFUR). Percent free cortisol and free cortisol concentration (FF) was determined by equilibrium dialysis at 37 C. 169 plasma samples with an F range of 0.8-61.2 mug/100 ml from 18 normal, 10 ACTH-stimulated, 17 estrogen-treated and 12 pregnant subjects were analyzed. A highly significant correlation between FFI and FF was found (r = 0.952). Inter-assay coefficients of variation were 7% for total plasma F and 3.5% for CFU. The method allows the rapid processing of large numbers of samples and can be performed on 0.2 ml of plasma."} {"id": "PMID:163846", "title": "Growth hormone release after synthetic 1-24 ACTH: effects of estrogen and sex.", "content": "Recent reports have demonstrated that growth hormone (GH) is inconsistently released after intravenous administration of synthetic 1-24 ACTH. This study was designed to evaluate the role of estrogens in mediating this response. 250 mug of synthetic 1-24 ACTH were administered to 8 men in 12 studies and 6 women in 11 studies. None of the men exhibited a rise in GH after 1-24 ACTH, while the women exhibited a significant increase. Pretreatment of 5 of these men with 100 mug of ethinyl estradiol daily for 3 days did not alter GH response from the initial studies. Pretreatment with 10 mg of diethylstilbesterol daily for 3 days, however, resulted in a rise in GH which was similar to the female group. It is concluded that the variable GH responses to synthetic 1-24 ACTH may be in part due to prevailing concentrations of sex steroids and their effect on the hypothalamic-pituitary GH release mechanism.", "contents": "Growth hormone release after synthetic 1-24 ACTH: effects of estrogen and sex. Recent reports have demonstrated that growth hormone (GH) is inconsistently released after intravenous administration of synthetic 1-24 ACTH. This study was designed to evaluate the role of estrogens in mediating this response. 250 mug of synthetic 1-24 ACTH were administered to 8 men in 12 studies and 6 women in 11 studies. None of the men exhibited a rise in GH after 1-24 ACTH, while the women exhibited a significant increase. Pretreatment of 5 of these men with 100 mug of ethinyl estradiol daily for 3 days did not alter GH response from the initial studies. Pretreatment with 10 mg of diethylstilbesterol daily for 3 days, however, resulted in a rise in GH which was similar to the female group. It is concluded that the variable GH responses to synthetic 1-24 ACTH may be in part due to prevailing concentrations of sex steroids and their effect on the hypothalamic-pituitary GH release mechanism."} {"id": "PMID:163847", "title": "Antagonism of the antibacterial action of some penicillins by other penicillins and cephalosporins.", "content": "There are many examples of two penicillins acting synergistically, usually by one competitively inhibiting beta-lactamase, thus protecting the other from inactivation. There are few reports on penicillins antagonizing each other. Eight strains of three genera (Proteus, Escherichia, Pseudomonas) isolated at Boston City Hospital or Institut Pasteur, Paris, showed antagonism of carbenicillin or ampicillin by cephaloridine, cloxacillin, or 6-aminopenicillanic acid. Broth dilution tests showed that with seven of the eight strains the minimum inhibiting concentration (MIC) of the more active antibiotic was increased by 800-6,400% by low concentrations (often one-tenth the MIC) of the antagonist, whereas higher concentrations of \"antagonist\" were not as antagonistic, This suggested that two or more receptor sites of action for penicillins were present; the antagonist thus blocks the antibacterial action at the more sensitive site but acts additively with the antagonized antibiotic at the less sensitive site. The possibility that the mechanism of antagonism was induction of inactivating enzymes (beta-lactamase, penicillin acylase) was studied in two strains(one Escherichia coli and one Proteus rettgeri), and two antagonists were studied in detail. With E. coli cephaloridine was a poorer inducer of beta-lactamase than were the antagonized antibiotic and 6-aminopenicillanic acid. From these organisms, the good inducers of a beta-lactamase that acted on benzylpenicillin did not induce enzymes that inactivated carbenicillin. Thus, the mechanism of antagonism was not due to beta-lactamase induction.", "contents": "Antagonism of the antibacterial action of some penicillins by other penicillins and cephalosporins. There are many examples of two penicillins acting synergistically, usually by one competitively inhibiting beta-lactamase, thus protecting the other from inactivation. There are few reports on penicillins antagonizing each other. Eight strains of three genera (Proteus, Escherichia, Pseudomonas) isolated at Boston City Hospital or Institut Pasteur, Paris, showed antagonism of carbenicillin or ampicillin by cephaloridine, cloxacillin, or 6-aminopenicillanic acid. Broth dilution tests showed that with seven of the eight strains the minimum inhibiting concentration (MIC) of the more active antibiotic was increased by 800-6,400% by low concentrations (often one-tenth the MIC) of the antagonist, whereas higher concentrations of \"antagonist\" were not as antagonistic, This suggested that two or more receptor sites of action for penicillins were present; the antagonist thus blocks the antibacterial action at the more sensitive site but acts additively with the antagonized antibiotic at the less sensitive site. The possibility that the mechanism of antagonism was induction of inactivating enzymes (beta-lactamase, penicillin acylase) was studied in two strains(one Escherichia coli and one Proteus rettgeri), and two antagonists were studied in detail. With E. coli cephaloridine was a poorer inducer of beta-lactamase than were the antagonized antibiotic and 6-aminopenicillanic acid. From these organisms, the good inducers of a beta-lactamase that acted on benzylpenicillin did not induce enzymes that inactivated carbenicillin. Thus, the mechanism of antagonism was not due to beta-lactamase induction."} {"id": "PMID:163848", "title": "Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients.", "content": "All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent \"blinded\" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.", "contents": "Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent \"blinded\" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU."} {"id": "PMID:163849", "title": "Collagen in the human lung. Quantitation of rates of synthesis and partial characterization of composition.", "content": "The presence of collagen in lung is fundamental in normal lung structure and function. Methods have been developed to examine human fetal and adult lung collagen with respect to its composition and synthesis. The second trimester fetal lung has a large number of cells per unit lung mass (36.6 plus or minus 2.7 mug DNA/mg dry wt) and relatively small amounts of collagen (17.0 plus or minus 5.3 mug collagen/mg dry wt). The number of cells per unit lung mass in the adult lung (11.1 plus or minus 3.4 mug DNA/mg dry wt) is 30% of the number of cells in the fetal lung, but the adult has 11 times more collagen (196 plus or minus 25 mug collagen/mg dry wt). The composition of fetal lung collagen can be partially characterized by extraction with salt at neutral pH, acetic acid, or guanidine. The extracted chains, representing 10% of the total lung collagen, chromatograph as alpha1 and alpha2 chains, each with a mol wt of 100,000 and an animo acid composition characteristic for collagen but not specific for lung. Short-term explant cultures of fetal and adult lung synthesize alpha chains which can be isolated by ion-exchange chromatography. These chains, representing 30-40% of the total collagen synthesized by the explants, coelectrophorese with extracted collagen chains on acrylamide gels: they are destroyed by clostridial collagenase and they have a mol wt of 100,000. Although the composition of the collagen synthesized by these explants can be only partially characterized, the rate of synthesis of both collagen and noncollagen protein can be quantitated. In fetal lung, 4.0 plus or minus 1.2% of the amino acids incorporated into protein per hour are incorporated into collagen. In normal adult lung, this percentage (4.2 plus or minus 0.9%) is remarkably similar. These values are almost identical to the relative rate of collagen synthesis in rabbit lung in the same age range. This technology should be applicable to answer specific questions regarding collagen synthesis and degradation in human lung disease.", "contents": "Collagen in the human lung. Quantitation of rates of synthesis and partial characterization of composition. The presence of collagen in lung is fundamental in normal lung structure and function. Methods have been developed to examine human fetal and adult lung collagen with respect to its composition and synthesis. The second trimester fetal lung has a large number of cells per unit lung mass (36.6 plus or minus 2.7 mug DNA/mg dry wt) and relatively small amounts of collagen (17.0 plus or minus 5.3 mug collagen/mg dry wt). The number of cells per unit lung mass in the adult lung (11.1 plus or minus 3.4 mug DNA/mg dry wt) is 30% of the number of cells in the fetal lung, but the adult has 11 times more collagen (196 plus or minus 25 mug collagen/mg dry wt). The composition of fetal lung collagen can be partially characterized by extraction with salt at neutral pH, acetic acid, or guanidine. The extracted chains, representing 10% of the total lung collagen, chromatograph as alpha1 and alpha2 chains, each with a mol wt of 100,000 and an animo acid composition characteristic for collagen but not specific for lung. Short-term explant cultures of fetal and adult lung synthesize alpha chains which can be isolated by ion-exchange chromatography. These chains, representing 30-40% of the total collagen synthesized by the explants, coelectrophorese with extracted collagen chains on acrylamide gels: they are destroyed by clostridial collagenase and they have a mol wt of 100,000. Although the composition of the collagen synthesized by these explants can be only partially characterized, the rate of synthesis of both collagen and noncollagen protein can be quantitated. In fetal lung, 4.0 plus or minus 1.2% of the amino acids incorporated into protein per hour are incorporated into collagen. In normal adult lung, this percentage (4.2 plus or minus 0.9%) is remarkably similar. These values are almost identical to the relative rate of collagen synthesis in rabbit lung in the same age range. This technology should be applicable to answer specific questions regarding collagen synthesis and degradation in human lung disease."} {"id": "PMID:163850", "title": "Treatment and control of neonatal diarrhea in calves.", "content": "Treatment and control of acute neonatal diarrhea in calves are outlined and discussed. The difficulty in making a definitive etiological diagnosis makes effective treatment and control also difficult and largely empirical. Physiological events in calves with diarrhea are known, and fluid therapy is directed toward treating dehydration and acidosis. Whether affected calves should receive antibacterial agents orally is an open question. Principles of control of diarrhea in calves are outlined and discussed.", "contents": "Treatment and control of neonatal diarrhea in calves. Treatment and control of acute neonatal diarrhea in calves are outlined and discussed. The difficulty in making a definitive etiological diagnosis makes effective treatment and control also difficult and largely empirical. Physiological events in calves with diarrhea are known, and fluid therapy is directed toward treating dehydration and acidosis. Whether affected calves should receive antibacterial agents orally is an open question. Principles of control of diarrhea in calves are outlined and discussed."} {"id": "PMID:163855", "title": "Peptides with NH2-terminal tryptophan in adrenocorticotrophic hormone and melanocyte-stimulating hormone granules of adenohypophysis.", "content": "Fluorescence microscopy has demonstrated formaldehyde-ozone-induced fluorescence in the pars intermedia cells (melanocyte-stimulating hormone cells) and in certain cells of the pars distalis of the mammalian pituitary. From histochemical and chemical evidence the fluorescence is believed to reflect the presence of peptides with NH2-terminal tryptophan. In the pars distalis of hamster, cat and pig pituitary, the cells that exhibit formaldehyde-ozone-induced fluorescence have now been identified as adrenocorticotrophic hormone (ACTH) cells by immunohistochemistry. Granules from pig pituitaries were purified by passage through a succession of Millipore filters followed by centrifugation on a continuous sucrose gradient. Two granular fractions were identified by electron microscopy and found to contain high concentrations of peptides with NH2-terminal tryptophan as well as high ACTH bioactivity. These fractions, when pelleted and analyzed histochemically, displayed formaldehyde-ozone-induced fluorescence and ACTH-like immunoreactivity.", "contents": "Peptides with NH2-terminal tryptophan in adrenocorticotrophic hormone and melanocyte-stimulating hormone granules of adenohypophysis. Fluorescence microscopy has demonstrated formaldehyde-ozone-induced fluorescence in the pars intermedia cells (melanocyte-stimulating hormone cells) and in certain cells of the pars distalis of the mammalian pituitary. From histochemical and chemical evidence the fluorescence is believed to reflect the presence of peptides with NH2-terminal tryptophan. In the pars distalis of hamster, cat and pig pituitary, the cells that exhibit formaldehyde-ozone-induced fluorescence have now been identified as adrenocorticotrophic hormone (ACTH) cells by immunohistochemistry. Granules from pig pituitaries were purified by passage through a succession of Millipore filters followed by centrifugation on a continuous sucrose gradient. Two granular fractions were identified by electron microscopy and found to contain high concentrations of peptides with NH2-terminal tryptophan as well as high ACTH bioactivity. These fractions, when pelleted and analyzed histochemically, displayed formaldehyde-ozone-induced fluorescence and ACTH-like immunoreactivity."} {"id": "PMID:163856", "title": "Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells.", "content": "Normal guinea pig macrophages incubated for 3 days in vitro with mediator-rich lymphocyte supernatants become cytotoxic for the syngeneic tumors, line 1 hepatoma and MCA-25 fibrosarcoma. Under identical experimental conditions the survival of two normal syngeneic cell types, fibroblasts and kidney cells, was not affected. The activating supernatants were prepared by stimulating sensitized lymphocyte cultures with an antigen unrelated to the target cells. Therefore, this type of macrophage-mediated cytotoxicity appears to be nonspecific but restricted to cells with malignant growth capacities.", "contents": "Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells. Normal guinea pig macrophages incubated for 3 days in vitro with mediator-rich lymphocyte supernatants become cytotoxic for the syngeneic tumors, line 1 hepatoma and MCA-25 fibrosarcoma. Under identical experimental conditions the survival of two normal syngeneic cell types, fibroblasts and kidney cells, was not affected. The activating supernatants were prepared by stimulating sensitized lymphocyte cultures with an antigen unrelated to the target cells. Therefore, this type of macrophage-mediated cytotoxicity appears to be nonspecific but restricted to cells with malignant growth capacities."} {"id": "PMID:163857", "title": "Complement biosynthesis in vitro by rat hepatoma cell strains.", "content": "Four separate rat hepatoma strains were examined for their capacity to synthesize complement (C). None of the strains synthesized detectable amounts of the first components (C-1), and only one strain (7800C-1) produced the fourth component (C4). However, each of the strains synthesized significant amounts of biologically active C-2 and C-3. Three of the four strains also produced C-5 and the natural inhibitor of C-1 (C1 INH). Two control rat cell strains (fibroblast and pituitary) did not synthesize any detectable C components. Production of C, studied extensively in 7800C-1 and H-4, was reversibly inhibited by cycloheximide (2 mug/ml) and [ 14-C ] amino acids were incorporated into C-2, C-3, and C-1 INH. As assessed by gel filtration, the elution positions of the C components synthesized by the cells in culture were similar to those of the corresponding proteins in normal rat serum. Hydrocortisone (10-6 to 10-7 M) stimulated the production of C-3 by H-4 but C-2 and C-5 production were not affected. These C-producing hepatoma cells may prove useful for studies of the control of C biosynthesis.", "contents": "Complement biosynthesis in vitro by rat hepatoma cell strains. Four separate rat hepatoma strains were examined for their capacity to synthesize complement (C). None of the strains synthesized detectable amounts of the first components (C-1), and only one strain (7800C-1) produced the fourth component (C4). However, each of the strains synthesized significant amounts of biologically active C-2 and C-3. Three of the four strains also produced C-5 and the natural inhibitor of C-1 (C1 INH). Two control rat cell strains (fibroblast and pituitary) did not synthesize any detectable C components. Production of C, studied extensively in 7800C-1 and H-4, was reversibly inhibited by cycloheximide (2 mug/ml) and [ 14-C ] amino acids were incorporated into C-2, C-3, and C-1 INH. As assessed by gel filtration, the elution positions of the C components synthesized by the cells in culture were similar to those of the corresponding proteins in normal rat serum. Hydrocortisone (10-6 to 10-7 M) stimulated the production of C-3 by H-4 but C-2 and C-5 production were not affected. These C-producing hepatoma cells may prove useful for studies of the control of C biosynthesis."} {"id": "PMID:163858", "title": "Regulation of the in vitro early anamnestic antibody response by exogenous cholera enterotoxin and cyclic AMP.", "content": "Keyhole limpet hemocyanin was injected into the hind foot pads of rabbits. Six days later cell suspensions were prepared from the popliteal lymph nodes. Various amounts of hemocyanin (1 ng to 100 mug) were added to 1 times 10-7 cells to induce an anamnestic antibody response. Various amounts of cholera enterotoxin, which stimulates the enzyme adenylate cyclase, or dibutyryl cyclic adenosine 3'5'-monophosphate (AMP), were added to the cultures with or without hemocyanin. De novo synthesis of antibody, protein, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from radioactive precursors was assayed. The addition of cholera toxin or dibutyryl cyclic AMP for the first 24 hr with optimal (1 mug) or supraoptimal (100 mug) amounts of hemocyanin enhanced antibody synthesis by at least 100 to 200%. Addition of the toxin or dibutyryl cyclic AMP for the same period to cells minus hemocyanin or with suboptimal amounts (1 to 100 ng) of antigen failed to enhance antibody synthesis. Addition of these agents for 72 to 120 hr to hemocyanin-induced cultures consistently inhibited antibody synthesis. These agents slightly inhibited DNA and RNA synthesis. The increase in protein synthesis caused by the toxin or dibutyryl cyclic AMP was almost totally accounted for by the increase in antibody synthesis. Neither toxin nor cyclic nucleotide promoted the antibody response in the presence of antibody to rabbit thymus-derived lymphocytes; these lymphocytes as well as bursa-equivalent lymphocytes were required for potentiation of the response. Macrophages were not required either for induction of the anamnestic response or for enhancement of this synthesis by cyclic nucleotide or cholera toxin. Both IgM and IgG antibody synthesis were regulated by exogenous cholera toxin and dibutyryl cyclic AMP. A number of possible cellular mechanisms of regulation of the antibody response through the cyclic AMP pathway were discussed. These included the effects of modifications of this pathway on the activities of T lymphocytes early (0 to 24 hr) and B lymphocytes late (72 to 120 hr) in the response and on the apparent reversal of high zone tolerance.", "contents": "Regulation of the in vitro early anamnestic antibody response by exogenous cholera enterotoxin and cyclic AMP. Keyhole limpet hemocyanin was injected into the hind foot pads of rabbits. Six days later cell suspensions were prepared from the popliteal lymph nodes. Various amounts of hemocyanin (1 ng to 100 mug) were added to 1 times 10-7 cells to induce an anamnestic antibody response. Various amounts of cholera enterotoxin, which stimulates the enzyme adenylate cyclase, or dibutyryl cyclic adenosine 3'5'-monophosphate (AMP), were added to the cultures with or without hemocyanin. De novo synthesis of antibody, protein, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from radioactive precursors was assayed. The addition of cholera toxin or dibutyryl cyclic AMP for the first 24 hr with optimal (1 mug) or supraoptimal (100 mug) amounts of hemocyanin enhanced antibody synthesis by at least 100 to 200%. Addition of the toxin or dibutyryl cyclic AMP for the same period to cells minus hemocyanin or with suboptimal amounts (1 to 100 ng) of antigen failed to enhance antibody synthesis. Addition of these agents for 72 to 120 hr to hemocyanin-induced cultures consistently inhibited antibody synthesis. These agents slightly inhibited DNA and RNA synthesis. The increase in protein synthesis caused by the toxin or dibutyryl cyclic AMP was almost totally accounted for by the increase in antibody synthesis. Neither toxin nor cyclic nucleotide promoted the antibody response in the presence of antibody to rabbit thymus-derived lymphocytes; these lymphocytes as well as bursa-equivalent lymphocytes were required for potentiation of the response. Macrophages were not required either for induction of the anamnestic response or for enhancement of this synthesis by cyclic nucleotide or cholera toxin. Both IgM and IgG antibody synthesis were regulated by exogenous cholera toxin and dibutyryl cyclic AMP. A number of possible cellular mechanisms of regulation of the antibody response through the cyclic AMP pathway were discussed. These included the effects of modifications of this pathway on the activities of T lymphocytes early (0 to 24 hr) and B lymphocytes late (72 to 120 hr) in the response and on the apparent reversal of high zone tolerance."} {"id": "PMID:163859", "title": "Spleen cell-mediated cytotoxicity of hamster cells transformed by Herpes simplex virus: evidence for virus-specific membrane antigen.", "content": "The nature of the host's immune response to isografts of hamster embryo fibroblasts (HEF) transformed by herpes simplex virus type 1 (HSV-1) was investigated by the microcytotoxicity assay. It was found that spleen cells from tumor-bearing hamsters killed homologous tumor cells but not HEF transformed by cytomegalovirus or PARA-(defective SV40)-adenovirus 7 (PARA-7). Cytotoxicity was lost as the tumor increased in size. Spleen cells from animals bearing isografts of HSV type 2 (HSV-2) transformed cells also killed HSV-1 target cells whereas spleen cells from PARA-7 tumor bearers did not. Further studies showed that animals immunized with HSV-1 or HSV-1-infected rabbit kidney cells produced spleen cells specifically cytotoxic for HSV-transformed cells. On the other hand, sera from virus-immunized hosts or tumor bearers had no effect on the cells in the presence of guinea pig complement. However, in blocking experiments such sera could significantly reduce spleen cell cytotoxicity. These experiments established that cells transformed by HSV could elicit a cellular immune response in the syngeneic host, and provided evidence that the immunity was directed against virus-specific antigens on the cell surface.", "contents": "Spleen cell-mediated cytotoxicity of hamster cells transformed by Herpes simplex virus: evidence for virus-specific membrane antigen. The nature of the host's immune response to isografts of hamster embryo fibroblasts (HEF) transformed by herpes simplex virus type 1 (HSV-1) was investigated by the microcytotoxicity assay. It was found that spleen cells from tumor-bearing hamsters killed homologous tumor cells but not HEF transformed by cytomegalovirus or PARA-(defective SV40)-adenovirus 7 (PARA-7). Cytotoxicity was lost as the tumor increased in size. Spleen cells from animals bearing isografts of HSV type 2 (HSV-2) transformed cells also killed HSV-1 target cells whereas spleen cells from PARA-7 tumor bearers did not. Further studies showed that animals immunized with HSV-1 or HSV-1-infected rabbit kidney cells produced spleen cells specifically cytotoxic for HSV-transformed cells. On the other hand, sera from virus-immunized hosts or tumor bearers had no effect on the cells in the presence of guinea pig complement. However, in blocking experiments such sera could significantly reduce spleen cell cytotoxicity. These experiments established that cells transformed by HSV could elicit a cellular immune response in the syngeneic host, and provided evidence that the immunity was directed against virus-specific antigens on the cell surface."} {"id": "PMID:163861", "title": "Tumor development after polyoma infection in athymic nude mice.", "content": "Nude (nu/nu) mice in a CBA/H background show an age-dependent ssuceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/ + or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent perids for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/ + spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/ + but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/ + had comparable titers when measured early after infection but higher titers were observed in nu/ + later after infection.", "contents": "Tumor development after polyoma infection in athymic nude mice. Nude (nu/nu) mice in a CBA/H background show an age-dependent ssuceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/ + or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent perids for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/ + spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/ + but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/ + had comparable titers when measured early after infection but higher titers were observed in nu/ + later after infection."} {"id": "PMID:163862", "title": "Lysis of tumor cells by antibody and complement. II. Lack of correlation between amount of C4 and C3 fixed and cell lysis.", "content": "Two antigenically distinct diethylnitrosamine-induced guinea pig hepatoma cell lines, line-1 and line-10, sensitized with rabbit anti-Forssman or with tumor-specific antibody, were more susceptible to killing by human complement (HuC) than by guinea pig complement (GPC). This difference could not be ascribed to differences in the amount of C1, C4, and C3 fixed: millions of C4 and hundreds of thousands of C3 were detected on cells whether they were killed or not killed by the C sources. Tumor cells sensitized with anti-Forssman IgM antibody generally had more GP C4 and C3 than Hu C4 and C3 bound to their surfaces. Cells sensitized with anti-tumor antibody generally had more Hu C4 and C3 than GP C4 and C3 bound to their surfaces. The resistance to killing of nucleated cells by antibody and C may be due in part to intrinisic properties of the cell.", "contents": "Lysis of tumor cells by antibody and complement. II. Lack of correlation between amount of C4 and C3 fixed and cell lysis. Two antigenically distinct diethylnitrosamine-induced guinea pig hepatoma cell lines, line-1 and line-10, sensitized with rabbit anti-Forssman or with tumor-specific antibody, were more susceptible to killing by human complement (HuC) than by guinea pig complement (GPC). This difference could not be ascribed to differences in the amount of C1, C4, and C3 fixed: millions of C4 and hundreds of thousands of C3 were detected on cells whether they were killed or not killed by the C sources. Tumor cells sensitized with anti-Forssman IgM antibody generally had more GP C4 and C3 than Hu C4 and C3 bound to their surfaces. Cells sensitized with anti-tumor antibody generally had more Hu C4 and C3 than GP C4 and C3 bound to their surfaces. The resistance to killing of nucleated cells by antibody and C may be due in part to intrinisic properties of the cell."} {"id": "PMID:163863", "title": "Mechanism of the suppressive effect of interferon on antibody synthesis in vivo.", "content": "Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive \"memory\" cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 times 10-5 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation. In addition, the use of nonadherent spleen cell cultures from interferon-treated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble \"suppressive\" factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.", "contents": "Mechanism of the suppressive effect of interferon on antibody synthesis in vivo. Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive \"memory\" cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 times 10-5 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation. In addition, the use of nonadherent spleen cell cultures from interferon-treated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble \"suppressive\" factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression."} {"id": "PMID:163864", "title": "Release of cyclic AMP from macrophages by stimulation with prostaglandins.", "content": "The effect of various prostaglandins (PG)on the generation of cyclic AMP in rat peritoneal macrophages has been studied in vitro. PGE1 produced a rapid intracellular accumulation of cyclic AMP which was followed by its release into the extracellular space. More cyclic AMP was released with prostaglandins of the E-type than with A- and F-types. It is suggested that release of cyclic AMP from macrophages may participate in the modulation of leukocyte function.", "contents": "Release of cyclic AMP from macrophages by stimulation with prostaglandins. The effect of various prostaglandins (PG)on the generation of cyclic AMP in rat peritoneal macrophages has been studied in vitro. PGE1 produced a rapid intracellular accumulation of cyclic AMP which was followed by its release into the extracellular space. More cyclic AMP was released with prostaglandins of the E-type than with A- and F-types. It is suggested that release of cyclic AMP from macrophages may participate in the modulation of leukocyte function."} {"id": "PMID:163866", "title": "Lattice and rodlet nuclear inclusions in Merkel cells in rabbit epidermis.", "content": "A latticee or rodlet inclusion is occasionally observed in the nucleus of a Merkel cell. The lattice has the external form of a plaque or band and internally consists of alternating parallel wide and narrow layers. Filaments in wide layers run in at least two directions across the short dimension of the inclusion. In contrast, the rodlet is a bundle of parallel filaments running the long dimension of the inclusion. Filaments in lattices and rodlets possibly contract and agitate the highly folded nucleus of the Merkel cell.", "contents": "Lattice and rodlet nuclear inclusions in Merkel cells in rabbit epidermis. A latticee or rodlet inclusion is occasionally observed in the nucleus of a Merkel cell. The lattice has the external form of a plaque or band and internally consists of alternating parallel wide and narrow layers. Filaments in wide layers run in at least two directions across the short dimension of the inclusion. In contrast, the rodlet is a bundle of parallel filaments running the long dimension of the inclusion. Filaments in lattices and rodlets possibly contract and agitate the highly folded nucleus of the Merkel cell."} {"id": "PMID:163867", "title": "Susceptibility of anaerobic bacteria to metronidazole: relative resistance of non-spore-forming gram-positive baccilli.", "content": "Susceptibility of 358 clinical isolates of obligate anaerobes to metronidazole was determined by an agar-dilution technique. Only 66% of all isolates were inhibited by 6.25 mug/ml, whereas 30% required larger than or equal to 50 mug/ml. Considerable variation in susceptibility was observed among different genera and species of bacteria. Fusobacterium was most senstitive, followed by Clostridium, Bacteroides and Peptococcus, Peptostreptococcus, Veillonella and Acidaminococcus, and non-spore-forming gram-positive bacilli. Bacteroides fragilis was more sensitive than other species of Bacteroides. Similarly, Clostridium perfringens was more susceptible than other species of Clostriduim. While metronidazole appears to be a promising antimicrobial agent for infections caused by Fusobacterium, Clostrididium, and B.fragilis, therapy for infections with other anaerobic bacteria should be guided by in vitro tests of sensitiivity.", "contents": "Susceptibility of anaerobic bacteria to metronidazole: relative resistance of non-spore-forming gram-positive baccilli. Susceptibility of 358 clinical isolates of obligate anaerobes to metronidazole was determined by an agar-dilution technique. Only 66% of all isolates were inhibited by 6.25 mug/ml, whereas 30% required larger than or equal to 50 mug/ml. Considerable variation in susceptibility was observed among different genera and species of bacteria. Fusobacterium was most senstitive, followed by Clostridium, Bacteroides and Peptococcus, Peptostreptococcus, Veillonella and Acidaminococcus, and non-spore-forming gram-positive bacilli. Bacteroides fragilis was more sensitive than other species of Bacteroides. Similarly, Clostridium perfringens was more susceptible than other species of Clostriduim. While metronidazole appears to be a promising antimicrobial agent for infections caused by Fusobacterium, Clostrididium, and B.fragilis, therapy for infections with other anaerobic bacteria should be guided by in vitro tests of sensitiivity."} {"id": "PMID:163868", "title": "Psittacine herpesvirus infection resembling pacheco's parrot disease.", "content": "Herpesvirus was detected by electron microscopy in hepatocytes of psittacine birds that died at a Florida aviary. The virus was identified in hepatocytes of chick embryos and budgerigars that were given injections of liver suspensions from naturally infected psittacines. Infected hepatocytes had prominent intranuclear inclusions that contained naked nucleocapsids. Both naked and enveloped virions were seen in the cytoplasm of hepatocytes, and enveloped nucleocapsids occasionally were seen in the perinuclear cisternae and extracellularly. The experimental and spontaneous disease mimicked a condition in parrots described previously by Pacheco. The viral agent was classified as Herpesvirus on the bases of the character of the intranuclear inclusions, the size and conformation of the agent as determined by electron microscopy and filtration, and the sensitivity of the agent to ether.", "contents": "Psittacine herpesvirus infection resembling pacheco's parrot disease. Herpesvirus was detected by electron microscopy in hepatocytes of psittacine birds that died at a Florida aviary. The virus was identified in hepatocytes of chick embryos and budgerigars that were given injections of liver suspensions from naturally infected psittacines. Infected hepatocytes had prominent intranuclear inclusions that contained naked nucleocapsids. Both naked and enveloped virions were seen in the cytoplasm of hepatocytes, and enveloped nucleocapsids occasionally were seen in the perinuclear cisternae and extracellularly. The experimental and spontaneous disease mimicked a condition in parrots described previously by Pacheco. The viral agent was classified as Herpesvirus on the bases of the character of the intranuclear inclusions, the size and conformation of the agent as determined by electron microscopy and filtration, and the sensitivity of the agent to ether."} {"id": "PMID:163869", "title": "Seroepidemiologic study of Epstein-Barr virus infections in a rural community.", "content": "The prevalence and titers of antibodies to capsid antigens of Epstein-Barr virus ad to the diffuse and restricted components of the Epstein-Barr virus-induced early antigen complex were determined in 109 families of a semirural community in Louisiana. Titers of antibody to the capsid antigens larger than or equal to 10 were found in 84 percent of children aged two to five years, and the prevalence increased with age to nearly 100 percent. There was a positive but variable correlation of the prevalence of anti-capsid antigen reactivity with low socioeconomic status and crowding. An overrepresentation of high titers of antibody to capsid antigens was present in individuals with a past history of pneumonia and urinary tract infections. The geometric mean titers of antibody to capsid antigens were highest in early childhood, lowest in adolescence and young adulthood, and high in the elderly. Females in all age groups and tonsillectomized children showed a higher geometric mean titer than their male and nontonsillectomized counterparts, respectively. Antibodies to the early antigen complex were found rarely (8.2 percent) and only in sera with relatively high titers of antibody to capsid antigens.", "contents": "Seroepidemiologic study of Epstein-Barr virus infections in a rural community. The prevalence and titers of antibodies to capsid antigens of Epstein-Barr virus ad to the diffuse and restricted components of the Epstein-Barr virus-induced early antigen complex were determined in 109 families of a semirural community in Louisiana. Titers of antibody to the capsid antigens larger than or equal to 10 were found in 84 percent of children aged two to five years, and the prevalence increased with age to nearly 100 percent. There was a positive but variable correlation of the prevalence of anti-capsid antigen reactivity with low socioeconomic status and crowding. An overrepresentation of high titers of antibody to capsid antigens was present in individuals with a past history of pneumonia and urinary tract infections. The geometric mean titers of antibody to capsid antigens were highest in early childhood, lowest in adolescence and young adulthood, and high in the elderly. Females in all age groups and tonsillectomized children showed a higher geometric mean titer than their male and nontonsillectomized counterparts, respectively. Antibodies to the early antigen complex were found rarely (8.2 percent) and only in sera with relatively high titers of antibody to capsid antigens."} {"id": "PMID:163870", "title": "Herpes simplex virus microneutralization: a simplification of the test.", "content": "The herpes simplex virus (HSV) microneutralization test has been simplified; its use has been demonstrated for the identification of HSV isolates as type 1 (HSV-1) or type 2 (HSV-2) and for the measurement of antibodies to HSV-1 and HSV-2. In this test, the relation between the neutralization titer and virus input is linear, and thus test results can be expressed as corrected neutralization titers, rather than as the more complex neutralizing potency values previously proposed. By means of this test, 45 of 46 clinical isolates of HSV were unequivocally identified as either HSV-1 or HSV-2. Evaluation of neutralizing antibody to HSV infection was more difficult because some neutralizing antibody to the heterotypic HSV is produced after primary infection with HSV-1 or HSV-2, because patients previously infected with one HSV type may show a variety of serological responses to subsequent heterotypic infection, and because human sera obtained early after primary HSV infection may not yet exhibit a type-specific response.", "contents": "Herpes simplex virus microneutralization: a simplification of the test. The herpes simplex virus (HSV) microneutralization test has been simplified; its use has been demonstrated for the identification of HSV isolates as type 1 (HSV-1) or type 2 (HSV-2) and for the measurement of antibodies to HSV-1 and HSV-2. In this test, the relation between the neutralization titer and virus input is linear, and thus test results can be expressed as corrected neutralization titers, rather than as the more complex neutralizing potency values previously proposed. By means of this test, 45 of 46 clinical isolates of HSV were unequivocally identified as either HSV-1 or HSV-2. Evaluation of neutralizing antibody to HSV infection was more difficult because some neutralizing antibody to the heterotypic HSV is produced after primary infection with HSV-1 or HSV-2, because patients previously infected with one HSV type may show a variety of serological responses to subsequent heterotypic infection, and because human sera obtained early after primary HSV infection may not yet exhibit a type-specific response."} {"id": "PMID:163871", "title": "Differential action of deoxynucleosides on mammalian cell cultures infected with herpes simplex virus types 1 and 2.", "content": "Cytopathic effects induced by eight serologically defined isolates of herpes simplex virus type 2 (tested on human amnion cells) were markedly inhibited by thymidine at a concentration of 5 mM; eight serologically defined isolates of herpes simplex virus type 1, however, were not significantly inhibited. A similar effect was seen with thymidine, deoxyguanosine, and deoxycytidine at 1-mM concentrations in tests with rabbit kidney cultures. The inhibitory effect of thymidine was not blocked by the simultaneous presence of deoxycytidine, which has been shown by others to release mammalian cells from thymidine suppression. Differential suppression of herpes simplex cytopathic effects by these deoxynucleosides provides further evidence of biochemical differences between herpes simplex types 1 and 2. This phenomenon offers a basis for rapid differentiation of type 1 from type 2.", "contents": "Differential action of deoxynucleosides on mammalian cell cultures infected with herpes simplex virus types 1 and 2. Cytopathic effects induced by eight serologically defined isolates of herpes simplex virus type 2 (tested on human amnion cells) were markedly inhibited by thymidine at a concentration of 5 mM; eight serologically defined isolates of herpes simplex virus type 1, however, were not significantly inhibited. A similar effect was seen with thymidine, deoxyguanosine, and deoxycytidine at 1-mM concentrations in tests with rabbit kidney cultures. The inhibitory effect of thymidine was not blocked by the simultaneous presence of deoxycytidine, which has been shown by others to release mammalian cells from thymidine suppression. Differential suppression of herpes simplex cytopathic effects by these deoxynucleosides provides further evidence of biochemical differences between herpes simplex types 1 and 2. This phenomenon offers a basis for rapid differentiation of type 1 from type 2."} {"id": "PMID:163872", "title": "Virus-induced diabetes mellitus. III. Influence of the sex and strain of the host.", "content": "Nineteen inbred strains of male mice were infected with encephalomyocarditis virus. Five strains became hyperglycemic and had abnormal values in glucose tolerance tests; three strains remained normoglycemic but had abnormal values in glucose tolerance tests; and the remaining strains showed no abnormalities in blood glucose levels or glucose tolerance tests. Female mice from three of five strains tested also developed hyperglycemia, but in one strain (DBA/2) the hyperglycemia was less severe in females than in males. Castrated DBA/2 males developed less severe hyperglycemia than uncastrated males, even though the degree of damage to beta cells appeared to be similar in the two groups. Host factors apparently influence both the development and expression of virus-induced diabetes mellitus.", "contents": "Virus-induced diabetes mellitus. III. Influence of the sex and strain of the host. Nineteen inbred strains of male mice were infected with encephalomyocarditis virus. Five strains became hyperglycemic and had abnormal values in glucose tolerance tests; three strains remained normoglycemic but had abnormal values in glucose tolerance tests; and the remaining strains showed no abnormalities in blood glucose levels or glucose tolerance tests. Female mice from three of five strains tested also developed hyperglycemia, but in one strain (DBA/2) the hyperglycemia was less severe in females than in males. Castrated DBA/2 males developed less severe hyperglycemia than uncastrated males, even though the degree of damage to beta cells appeared to be similar in the two groups. Host factors apparently influence both the development and expression of virus-induced diabetes mellitus."} {"id": "PMID:163873", "title": "Temperature-sensitive viruses and the etiology of chronic and inapparent infections.", "content": "Several mechanisms have been put forward to explain how persistently infected virus-carrier cell cultures are maintained. In this report, information is summarized which suggests that selection of temperature-sensitive mutants may be involved in either establishment or maintenance of persistent infections both in cell cultures and in animals. The possible relation of this mechanism to other mechanisms of regulation of persistent infections is also discussed. Finally, a practical suggestion is offered to researchers and clinicians seeking endogenous viruses from cultured cells and tissues that may harbor temperature-sensitive variants.", "contents": "Temperature-sensitive viruses and the etiology of chronic and inapparent infections. Several mechanisms have been put forward to explain how persistently infected virus-carrier cell cultures are maintained. In this report, information is summarized which suggests that selection of temperature-sensitive mutants may be involved in either establishment or maintenance of persistent infections both in cell cultures and in animals. The possible relation of this mechanism to other mechanisms of regulation of persistent infections is also discussed. Finally, a practical suggestion is offered to researchers and clinicians seeking endogenous viruses from cultured cells and tissues that may harbor temperature-sensitive variants."} {"id": "PMID:163874", "title": "Connective tissue activation. VII. Evidence supporting a role for prostaglandins and cyclic nucleotides.", "content": "Prostaglandins added to synovial cultures stimulated hyaluronic acid (HA) synthesis and glycolysis. The order of potency of the prostaglandins was: PGE1 greater than PGE2 greater than PGF2alpha greater than PGF1alpha, PGE1 and PGE2, 1.0 mug per milliliter, stimulated synovial cells, whereas F-series prostaglandins required 5 mug per milliliter for stimulation. Connective tissue-activating peptide (CTAP) activation of synovial cells was markedly potentiated by all four prostaglandins, and by PGE1 in concentrations as low as 0.01 mug per milliliter. Exogenous prostaglandins caused a prompt and marked increment in synovial cell cyclic-AMP, while CTAP caused a delayed peak of cyclic-AMP of lesser magnitude. Treatment of synovial cultures with cortisol (1.0 mug per milliliter), cycloheximide (10 mug per milliliter), or indomethacin (15.0 mug per milliliter) failed to block stimulation by PGE1, 7-OXA-13-Prostynoic acid, a prostaglandin antagonist, substantially inhibited the action of PGE1 and suppressed the effect of CTAP on synovial cells. It is possible that both exogenous and endogenous (synovial prostaglandins are involved in the connective tissue activation sequence.", "contents": "Connective tissue activation. VII. Evidence supporting a role for prostaglandins and cyclic nucleotides. Prostaglandins added to synovial cultures stimulated hyaluronic acid (HA) synthesis and glycolysis. The order of potency of the prostaglandins was: PGE1 greater than PGE2 greater than PGF2alpha greater than PGF1alpha, PGE1 and PGE2, 1.0 mug per milliliter, stimulated synovial cells, whereas F-series prostaglandins required 5 mug per milliliter for stimulation. Connective tissue-activating peptide (CTAP) activation of synovial cells was markedly potentiated by all four prostaglandins, and by PGE1 in concentrations as low as 0.01 mug per milliliter. Exogenous prostaglandins caused a prompt and marked increment in synovial cell cyclic-AMP, while CTAP caused a delayed peak of cyclic-AMP of lesser magnitude. Treatment of synovial cultures with cortisol (1.0 mug per milliliter), cycloheximide (10 mug per milliliter), or indomethacin (15.0 mug per milliliter) failed to block stimulation by PGE1, 7-OXA-13-Prostynoic acid, a prostaglandin antagonist, substantially inhibited the action of PGE1 and suppressed the effect of CTAP on synovial cells. It is possible that both exogenous and endogenous (synovial prostaglandins are involved in the connective tissue activation sequence."} {"id": "PMID:163875", "title": "Anion excretion pattern following infusion of hyperoncotic human serum albumin into dogs.", "content": "The effects of hyperoncotic human serum albumin on the excretion rates of several electrolytes and cyclic-AMP were measured in mongrel dogs and the results were compared with those obtained after the infusion of saline. Hyperoncotic albumin increased the excretion rates of sodium, potassium, bicarbonate, and phosphate. There was a small increase in chloride excretion after albumin, while there was a significant decrease in the rate of excretion of cyclic-AMP. Saline, on the other hand, caused a marked increase in the rate of of excretion of all the measured ions. Like albumin, saline was associated with a decrease in the rate of excretion of cyclic-AMP. The marked increase in bicarbonate and phosphate excretion suggests that the response to albumin which includes decreased isotonic reabsorption in the proximal tubule and increased urinary sodium excretion could result from decreased reabsorption in the proximal tubule accompanied by distal sodium and chloride reabsorption. Saline, on the other hand, caused a greater increase in sodium excretion and, although phosphate and bicarbonate excretion also increased, a much greater effect on the excretion of chloride was observed, suggesting that saline may also decrease sodium and chloride reabsorption in the distal nephron.", "contents": "Anion excretion pattern following infusion of hyperoncotic human serum albumin into dogs. The effects of hyperoncotic human serum albumin on the excretion rates of several electrolytes and cyclic-AMP were measured in mongrel dogs and the results were compared with those obtained after the infusion of saline. Hyperoncotic albumin increased the excretion rates of sodium, potassium, bicarbonate, and phosphate. There was a small increase in chloride excretion after albumin, while there was a significant decrease in the rate of excretion of cyclic-AMP. Saline, on the other hand, caused a marked increase in the rate of of excretion of all the measured ions. Like albumin, saline was associated with a decrease in the rate of excretion of cyclic-AMP. The marked increase in bicarbonate and phosphate excretion suggests that the response to albumin which includes decreased isotonic reabsorption in the proximal tubule and increased urinary sodium excretion could result from decreased reabsorption in the proximal tubule accompanied by distal sodium and chloride reabsorption. Saline, on the other hand, caused a greater increase in sodium excretion and, although phosphate and bicarbonate excretion also increased, a much greater effect on the excretion of chloride was observed, suggesting that saline may also decrease sodium and chloride reabsorption in the distal nephron."} {"id": "PMID:163876", "title": "The large-scale isolation of renin-containing granules from rabbit renal cortex by zonal centrifugation.", "content": "A new method for the isolation of renin-containing granules from rabbit renal cortex by sequential two-dimensional centrifugation is presented. A mitochondrial fraction produced by preparative differential centrifugation was subjected to isopycnic centrifugation on combined discontinuous and linear density gradients in the same SZ-14 reorienting gradient zonal centrifuge rotor. Renin activity, as assayed by radioimmunoassay for angiotensin I, was localized in a region of the density gradient with a corresponding density of 1.196 Gm. per cubic centimeter or 1.53 M sucrose. The renin-containing granules were enriched 5.0-fold over whole homogenate levels, while peroxisomes were enriched 17.4-fold, lysosomes 23.4-fold, and mitochondria 4.3-fold. Electron microscopic examination of the fraction with highest renin activity showed a granular fraction almost free of contamination from other subcellular material. The data supports the view that renin-containing granules are a distinct subcellular particle. This new method for the large-scale isolation of renin-containing granules makes it possible to obtain the quantity of material necessary to study the release renin at the subcellular level and permit the further biochemical purification and characterization of the enzyme.", "contents": "The large-scale isolation of renin-containing granules from rabbit renal cortex by zonal centrifugation. A new method for the isolation of renin-containing granules from rabbit renal cortex by sequential two-dimensional centrifugation is presented. A mitochondrial fraction produced by preparative differential centrifugation was subjected to isopycnic centrifugation on combined discontinuous and linear density gradients in the same SZ-14 reorienting gradient zonal centrifuge rotor. Renin activity, as assayed by radioimmunoassay for angiotensin I, was localized in a region of the density gradient with a corresponding density of 1.196 Gm. per cubic centimeter or 1.53 M sucrose. The renin-containing granules were enriched 5.0-fold over whole homogenate levels, while peroxisomes were enriched 17.4-fold, lysosomes 23.4-fold, and mitochondria 4.3-fold. Electron microscopic examination of the fraction with highest renin activity showed a granular fraction almost free of contamination from other subcellular material. The data supports the view that renin-containing granules are a distinct subcellular particle. This new method for the large-scale isolation of renin-containing granules makes it possible to obtain the quantity of material necessary to study the release renin at the subcellular level and permit the further biochemical purification and characterization of the enzyme."} {"id": "PMID:163877", "title": "Studies on the binding of 125I-labelled corticotrophin to isolated rat adrenocortical cells.", "content": "Isolated adrenocortical cells, prepared by collagenase disaggregation of normal rat adrenal glands, have been used to study the binding characteristics of 125I-labelled corticotrophin (ACTH) of established biological activity. The binding of the labelled hormone to these whole cells was highly specific, only peptides possessing steroidogenic activity displaced the labelled hormone. Binding was rapid, being complete within 5 min of adding the hormone, and the amount of hormone bound remained constant for up to 20 min thereafter. Over the range 160-10000pg ACTH/ml, increased binding of the hormone was observed at all concentrations of hormone which stimulated steroidogenesis. However at levels of ACTH which stimulated maximal steroidogenesis there was no saturation of binding. This provides the first direct evidence for the existence of 'spare receptors' for ACTH on whole adrenocortical cells. Scatchard analysis of the binding data suggests that there are two types of receptor for ACTH in this preparation of cells. One receptor is of high affinity (dissociation constant equals 2-5 times 10-10 mol/l) with about 3000 sites/cell and the other is of lower affinity (dissociation constant equals 1 times 10-8 mol/l) with about 30000 sites/cell.", "contents": "Studies on the binding of 125I-labelled corticotrophin to isolated rat adrenocortical cells. Isolated adrenocortical cells, prepared by collagenase disaggregation of normal rat adrenal glands, have been used to study the binding characteristics of 125I-labelled corticotrophin (ACTH) of established biological activity. The binding of the labelled hormone to these whole cells was highly specific, only peptides possessing steroidogenic activity displaced the labelled hormone. Binding was rapid, being complete within 5 min of adding the hormone, and the amount of hormone bound remained constant for up to 20 min thereafter. Over the range 160-10000pg ACTH/ml, increased binding of the hormone was observed at all concentrations of hormone which stimulated steroidogenesis. However at levels of ACTH which stimulated maximal steroidogenesis there was no saturation of binding. This provides the first direct evidence for the existence of 'spare receptors' for ACTH on whole adrenocortical cells. Scatchard analysis of the binding data suggests that there are two types of receptor for ACTH in this preparation of cells. One receptor is of high affinity (dissociation constant equals 2-5 times 10-10 mol/l) with about 3000 sites/cell and the other is of lower affinity (dissociation constant equals 1 times 10-8 mol/l) with about 30000 sites/cell."} {"id": "PMID:163880", "title": "Adrenocorticotrophin and the development of insulin secretion in the rabbit foetus.", "content": "Foetal rabbits were injected with adrenocorticotrophin (ACTH), decapitated, or decapitated and injected simultaneously with ACTH or cortisol in utero on day 24 of gestation. The foetuses were killed after Caesarian section on day 29, and blood was collected for measurement of plasma insulin concentration and pancreatic tissue was obtained for incubation in physiological buffer. Insulin release from the pancreatic tissue of decapitated foetuses was significantly greater than that from the pancreas of control litter-mates when incubated in media containing 3-3mM-glucose, 16-5mM-glucose or 16-5mM-glucose plus 5 mug glucagon/ml, but was similar when the incubation medium contained 3-3 or 16-5 mM-glucose plus 1 mM-theophylline or 3-3mM-glucose plus 60 mM-potassium. The pancreata of decapitated or intact foetuses injected with ACTH did not differ significantly from control foetuses in terms of insulin release in response to glucose in vitro. The plasma insulin concentration of decapitated foetuses and decapitated foetuses injected with ACTH was raised, whereas that of intact foetuses injected with ACTH was similar to that of the control foetuses. Cortisol injection at the time of decapitation resulted in a high rate of foetal mortality. The results indicate that foetal ACTH or foetal adrenocortical secretion influences the normal development of glucose-mediated insulin secretion in the rabbit and that exogenous ACTH corrects the effect of decapitation on beta cell function in vitro but not on plasma insulin concentration.", "contents": "Adrenocorticotrophin and the development of insulin secretion in the rabbit foetus. Foetal rabbits were injected with adrenocorticotrophin (ACTH), decapitated, or decapitated and injected simultaneously with ACTH or cortisol in utero on day 24 of gestation. The foetuses were killed after Caesarian section on day 29, and blood was collected for measurement of plasma insulin concentration and pancreatic tissue was obtained for incubation in physiological buffer. Insulin release from the pancreatic tissue of decapitated foetuses was significantly greater than that from the pancreas of control litter-mates when incubated in media containing 3-3mM-glucose, 16-5mM-glucose or 16-5mM-glucose plus 5 mug glucagon/ml, but was similar when the incubation medium contained 3-3 or 16-5 mM-glucose plus 1 mM-theophylline or 3-3mM-glucose plus 60 mM-potassium. The pancreata of decapitated or intact foetuses injected with ACTH did not differ significantly from control foetuses in terms of insulin release in response to glucose in vitro. The plasma insulin concentration of decapitated foetuses and decapitated foetuses injected with ACTH was raised, whereas that of intact foetuses injected with ACTH was similar to that of the control foetuses. Cortisol injection at the time of decapitation resulted in a high rate of foetal mortality. The results indicate that foetal ACTH or foetal adrenocortical secretion influences the normal development of glucose-mediated insulin secretion in the rabbit and that exogenous ACTH corrects the effect of decapitation on beta cell function in vitro but not on plasma insulin concentration."} {"id": "PMID:163882", "title": "Effects of hypothalamic extract and dibutyryl cyclic adenosine monophosphate on follicle-stimulating hormone production in the rat adenohypophysis in vitro.", "content": "An assay system, using the characteristic migration of follicle-stimulating hormone (FSH) on polyacrylamide gels, was developed to evaluate the effects of hypothalamic factors on amino acid incorporation into FSH in the rat adenohypophysis incubated in vitro. Follicle-stimulating hormone extracted from rat pituitary secretory granules was found to migrate on 7-5% polyacrylamide gels, pH 9-5, as a protein with an Rf of 0-614. The characteristic Rf was used to measure [14C]amino acid incorpotation into FSH in rat adenohypophyses in vitro. Follicle-stimulating hormone synthesis increased after addition of crude hypothalamic extract to the incubation medium. Hormone synthesis was also increased three times after the addition of dibutyryl cyclic AMP.", "contents": "Effects of hypothalamic extract and dibutyryl cyclic adenosine monophosphate on follicle-stimulating hormone production in the rat adenohypophysis in vitro. An assay system, using the characteristic migration of follicle-stimulating hormone (FSH) on polyacrylamide gels, was developed to evaluate the effects of hypothalamic factors on amino acid incorporation into FSH in the rat adenohypophysis incubated in vitro. Follicle-stimulating hormone extracted from rat pituitary secretory granules was found to migrate on 7-5% polyacrylamide gels, pH 9-5, as a protein with an Rf of 0-614. The characteristic Rf was used to measure [14C]amino acid incorpotation into FSH in rat adenohypophyses in vitro. Follicle-stimulating hormone synthesis increased after addition of crude hypothalamic extract to the incubation medium. Hormone synthesis was also increased three times after the addition of dibutyryl cyclic AMP."} {"id": "PMID:163883", "title": "Comparative effect of insulin and explanted adrenal medullary tissue and rat adrenal medulla in situ.", "content": "The adrenal medulla and explanted medullary cells in the anterior chamber of the eye were examined 3 h after the administration of insulin to rats. No alterations were seen in the explanted cells. In the adrenal medulla, light and electron microscopy indicated depletion of adrenaline cells; noradrenaline cells were not affected. Levels of catecholamines were three times higher in the explanted tissue after insulin treatment; in the medulla in situ they declined by 70%. These results confirm that insulin has no direct releasing effect on chromaffin cells.", "contents": "Comparative effect of insulin and explanted adrenal medullary tissue and rat adrenal medulla in situ. The adrenal medulla and explanted medullary cells in the anterior chamber of the eye were examined 3 h after the administration of insulin to rats. No alterations were seen in the explanted cells. In the adrenal medulla, light and electron microscopy indicated depletion of adrenaline cells; noradrenaline cells were not affected. Levels of catecholamines were three times higher in the explanted tissue after insulin treatment; in the medulla in situ they declined by 70%. These results confirm that insulin has no direct releasing effect on chromaffin cells."} {"id": "PMID:163885", "title": "Biochemical evidence linking the GIX thymocyte surface antigen to the gp69/71 envelope glycoprotein of murine leukemia virus.", "content": "It is known that the thymocyte surface antigen GIX is found in some strains of mice and not others, and that its expression in mice of strain 129, in which most extensive genetic studies have been made, is controlled by two unlinked cellular chromosomal loci. We have now isolated a protein with a mol wt of approximately 70,000 daltons from the surface of thymocytes from 129 mice, which have antigenic and biochemical properties characteristic of the gp69/71 envelope component of murine leukemia virus. Our evidence is compatible with the conclusion that it carries the GIX antigen.", "contents": "Biochemical evidence linking the GIX thymocyte surface antigen to the gp69/71 envelope glycoprotein of murine leukemia virus. It is known that the thymocyte surface antigen GIX is found in some strains of mice and not others, and that its expression in mice of strain 129, in which most extensive genetic studies have been made, is controlled by two unlinked cellular chromosomal loci. We have now isolated a protein with a mol wt of approximately 70,000 daltons from the surface of thymocytes from 129 mice, which have antigenic and biochemical properties characteristic of the gp69/71 envelope component of murine leukemia virus. Our evidence is compatible with the conclusion that it carries the GIX antigen."} {"id": "PMID:163886", "title": "The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis.", "content": "The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide.", "contents": "The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis. The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide."} {"id": "PMID:163887", "title": "Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction.", "content": "After infection in utero or at birth with a cell culture adapted strain of mouse cytomegalovirus (MCMV), several mouse strains developed a latent virus infection in the presence of specific antiviral antibodies. Up to 5 mo after infection, MCMV could be activated and recovered from spleen lymphocytes of the infected animals that were co-cultivated with histoincompatible (H-2 foreign) mouse embryo cells from uninfected animals. In contrast, co-cultivation of lymphoid cells from infected mice with mouse embryo cells from syngeneic, histocompatible (H-2 similar) donors did not activate MCMV. Similarly, MCMV was not recovered from sonicated lymphoid cells. Virus was activated by treating viable lymphoid cells with lipopolysaccharide, a B-cell mitogen, but was not activated by a variety of other mitogens such as phytohemagglutinin, concanavalin A, or pokeweed mitogen. Subsequent purification of lymphoid cells from the infected mice by a variety of techniques indicated that MCMV was harbored in the B-lymphocyte population.", "contents": "Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. After infection in utero or at birth with a cell culture adapted strain of mouse cytomegalovirus (MCMV), several mouse strains developed a latent virus infection in the presence of specific antiviral antibodies. Up to 5 mo after infection, MCMV could be activated and recovered from spleen lymphocytes of the infected animals that were co-cultivated with histoincompatible (H-2 foreign) mouse embryo cells from uninfected animals. In contrast, co-cultivation of lymphoid cells from infected mice with mouse embryo cells from syngeneic, histocompatible (H-2 similar) donors did not activate MCMV. Similarly, MCMV was not recovered from sonicated lymphoid cells. Virus was activated by treating viable lymphoid cells with lipopolysaccharide, a B-cell mitogen, but was not activated by a variety of other mitogens such as phytohemagglutinin, concanavalin A, or pokeweed mitogen. Subsequent purification of lymphoid cells from the infected mice by a variety of techniques indicated that MCMV was harbored in the B-lymphocyte population."} {"id": "PMID:163888", "title": "Isotope kinetics of human skin cholesterol secretion.", "content": "Specific radioactivity (SA) time curves of plasma and skin surface cholesterol collected at several skin areas were recorded in 10 patients on formula diets after single intravenous injections of radioactive cholesterol. Earliest detectable radioactivity on skin surface was found in 4-6 days; depending on the skin site, SA's peaked in 13-75 days. SA's of free cholesterol were almost always higher than those of esterified cholesterol. The general forms of the SA time curves were in keeping with the idea that plasma cholesterol is carried to the skin surface in association with the epidermal and sebaceous cells, whereby (a) cholesterol synthesized de novo is mixed with derived from plasma and (b) appearances of plasma cholesterol on the skin surface is delayed by a time factor that corresponds to the movement of epidermal and sebaceous cells from the basal layer to the skin surface. The shorter mean transit times of plasma cholesterol on skin areas rich in sebaceous glands (22-24 days on the head) than on those poor in these glands (38 days on forearms and 72 days on feet) suggest that cholesterol passes faster through the sebaceous glands than through the epidermis, and faster through thin than thick epidermis. The fraction of skin surface cholesterol (f) that is derived from plasma cholesterol was estimated by three independent methods, and comparable results were obtained. Values of f were lower on skin areas rich in sebaceous glands (0.29-0.46 on forehead) than on areas poor in these glands (0.41-0.70 for forearms; 0.60 on feet) and lower for esterified (0.27-0.33) than for free (0.39-0.48) cholesterol. These data suggest that higher proportions of sebaceous gland and of esterified cholesterol, respectively, are synthesized de novo than epidermal and of free cholesterol. In two patients it was possible to calculate that f of total skin surface cholesterol was 0.49 and 0.37, respectively, and that the maximum amount of plasma cholesterol lost through the skin was 29 and 22 mg/day, respectively. Knowing the total daily excretion of total neutral and acidic steroids in feces in these patients, and assuming a total daily urinary steroid excretion 50 mg, we estimated that no more than 3.2% of total steroid excretion occurred via the skin.", "contents": "Isotope kinetics of human skin cholesterol secretion. Specific radioactivity (SA) time curves of plasma and skin surface cholesterol collected at several skin areas were recorded in 10 patients on formula diets after single intravenous injections of radioactive cholesterol. Earliest detectable radioactivity on skin surface was found in 4-6 days; depending on the skin site, SA's peaked in 13-75 days. SA's of free cholesterol were almost always higher than those of esterified cholesterol. The general forms of the SA time curves were in keeping with the idea that plasma cholesterol is carried to the skin surface in association with the epidermal and sebaceous cells, whereby (a) cholesterol synthesized de novo is mixed with derived from plasma and (b) appearances of plasma cholesterol on the skin surface is delayed by a time factor that corresponds to the movement of epidermal and sebaceous cells from the basal layer to the skin surface. The shorter mean transit times of plasma cholesterol on skin areas rich in sebaceous glands (22-24 days on the head) than on those poor in these glands (38 days on forearms and 72 days on feet) suggest that cholesterol passes faster through the sebaceous glands than through the epidermis, and faster through thin than thick epidermis. The fraction of skin surface cholesterol (f) that is derived from plasma cholesterol was estimated by three independent methods, and comparable results were obtained. Values of f were lower on skin areas rich in sebaceous glands (0.29-0.46 on forehead) than on areas poor in these glands (0.41-0.70 for forearms; 0.60 on feet) and lower for esterified (0.27-0.33) than for free (0.39-0.48) cholesterol. These data suggest that higher proportions of sebaceous gland and of esterified cholesterol, respectively, are synthesized de novo than epidermal and of free cholesterol. In two patients it was possible to calculate that f of total skin surface cholesterol was 0.49 and 0.37, respectively, and that the maximum amount of plasma cholesterol lost through the skin was 29 and 22 mg/day, respectively. Knowing the total daily excretion of total neutral and acidic steroids in feces in these patients, and assuming a total daily urinary steroid excretion 50 mg, we estimated that no more than 3.2% of total steroid excretion occurred via the skin."} {"id": "PMID:163889", "title": "Regulation of protein phosphorylation and sodium transport in toad bladder.", "content": "It is well established that active sodium-ion transport and water flow across isolated toad bladder are increased by antidiuretic hormone (ADH) and by cAMP. These agents were also observed in previous studies to cause changes in the amount of radioactive phosphate in a specific protein in the toad bladder. This protein, found by SDS-polyacrylamide gel electrophoresis of toad bladder epithelial preparations, had an apparent molecular weight of 49,000 daltons. In the present study, a correlation was found between the ability of a variety of substances to affect the amount of radioactive phosphate in this 40,000-dalton protein and their ability to alter the rate of sodium transport. Thus several agents (ADH, cAMP, theophylline, adenine, prostaglandin E1, and Mn Cl-2) caused a decrease in the amount of radioactive phosphate in the 49,000-dalton protein and also stimulated active sodium transport across the bladder. Conversely, ZnCl-2 produced an increase in the amount of radioactive phosphate in this protein and an inhibition of sodium transport. With each of these agents, the time-course of change in phosphorylation of this protein was, in general, similar to that for sodium transport. A second phosphoprotein, with an apparent molecular weight of about 42,000 daltons, showed changes in parallel with, but less extensive than, those observed in the 49,000 dalton protein. There was no consistent relationship between changes in level of phosphorylation of either in the 49,000- or 42,000- dalton protein and changes in osmotic water permeability. The results are compatible with the possibility that regulation by ADH and by cAMP of sodium transport in the toad bladder epithelium may be mediated through regulation of the amount of phosphate in a specific protein.", "contents": "Regulation of protein phosphorylation and sodium transport in toad bladder. It is well established that active sodium-ion transport and water flow across isolated toad bladder are increased by antidiuretic hormone (ADH) and by cAMP. These agents were also observed in previous studies to cause changes in the amount of radioactive phosphate in a specific protein in the toad bladder. This protein, found by SDS-polyacrylamide gel electrophoresis of toad bladder epithelial preparations, had an apparent molecular weight of 49,000 daltons. In the present study, a correlation was found between the ability of a variety of substances to affect the amount of radioactive phosphate in this 40,000-dalton protein and their ability to alter the rate of sodium transport. Thus several agents (ADH, cAMP, theophylline, adenine, prostaglandin E1, and Mn Cl-2) caused a decrease in the amount of radioactive phosphate in the 49,000-dalton protein and also stimulated active sodium transport across the bladder. Conversely, ZnCl-2 produced an increase in the amount of radioactive phosphate in this protein and an inhibition of sodium transport. With each of these agents, the time-course of change in phosphorylation of this protein was, in general, similar to that for sodium transport. A second phosphoprotein, with an apparent molecular weight of about 42,000 daltons, showed changes in parallel with, but less extensive than, those observed in the 49,000 dalton protein. There was no consistent relationship between changes in level of phosphorylation of either in the 49,000- or 42,000- dalton protein and changes in osmotic water permeability. The results are compatible with the possibility that regulation by ADH and by cAMP of sodium transport in the toad bladder epithelium may be mediated through regulation of the amount of phosphate in a specific protein."} {"id": "PMID:163890", "title": "Threshold phenomena in chemoreception and taxis in slime mold Physarum polycephalum.", "content": "The plasmodium of Physarum polycephalum reacts to various kinds of chemicals substances and moves towards or away from them. Threshold concentration of recognition of chemicals was examined in terms of membrane potential and of the averaged motive force of tactic movement by using a double-chamber method, i.e., a single plasmodium was placed between two compartments through a narrow ditch, and differences in membrane potential and in pressure between two compartments were measured. Results are summarized as follows: (a) By increasing the concentration of various substances in one compartment, the membrane potential started to change at a certain threshold concentration, C-th, for each chemical. Chemotactic movement of the plasmodium took place at the same threshold concentration. These results held both for attractants (glucose, galactose, phosphates, pyrophosphates, ATP, c-AMP, etc) and for repellents (various inorganic salts, sucrose, fructose, etc.). (b) The threshold concentration, Cth, for inorganic salts decreased remarkably with increase of the valences of cations, zeta, and was proportional to Z-6, I.E., THE Shultze-Hardy rule known in the field of colloid chemistry was found to be applicable. (c) The plasmodium distinguished the species of monovalent cations in the following order: H(Li(K(Na(Rb(Cs(NH-4 Plots of log Cth against the lyotropic number of anion fell on different straight lines for each monovalent cation species. (d) Plots of log Cth, against the reciprocal of the absolute tempe lines were almost the same and gave a value of 12 kcal/mol for the enthalpy change. These results suggest that the recognition of chemical substances appears as the result of a structural change of the membrane at the threshold point, and that the change in membrane structure is transmitted simultaneously to the motile system of the plasmodium.", "contents": "Threshold phenomena in chemoreception and taxis in slime mold Physarum polycephalum. The plasmodium of Physarum polycephalum reacts to various kinds of chemicals substances and moves towards or away from them. Threshold concentration of recognition of chemicals was examined in terms of membrane potential and of the averaged motive force of tactic movement by using a double-chamber method, i.e., a single plasmodium was placed between two compartments through a narrow ditch, and differences in membrane potential and in pressure between two compartments were measured. Results are summarized as follows: (a) By increasing the concentration of various substances in one compartment, the membrane potential started to change at a certain threshold concentration, C-th, for each chemical. Chemotactic movement of the plasmodium took place at the same threshold concentration. These results held both for attractants (glucose, galactose, phosphates, pyrophosphates, ATP, c-AMP, etc) and for repellents (various inorganic salts, sucrose, fructose, etc.). (b) The threshold concentration, Cth, for inorganic salts decreased remarkably with increase of the valences of cations, zeta, and was proportional to Z-6, I.E., THE Shultze-Hardy rule known in the field of colloid chemistry was found to be applicable. (c) The plasmodium distinguished the species of monovalent cations in the following order: H(Li(K(Na(Rb(Cs(NH-4 Plots of log Cth against the lyotropic number of anion fell on different straight lines for each monovalent cation species. (d) Plots of log Cth, against the reciprocal of the absolute tempe lines were almost the same and gave a value of 12 kcal/mol for the enthalpy change. These results suggest that the recognition of chemical substances appears as the result of a structural change of the membrane at the threshold point, and that the change in membrane structure is transmitted simultaneously to the motile system of the plasmodium."} {"id": "PMID:163891", "title": "A dual synaptic effect on hair cells in Hermissenda.", "content": "Type A photorecptors can produce an initial hyperpolarizing wave followed by a delayed long-lasting increase in firing which is usually accompanied by a small depolarizing wave. The initial hyperpolarizing wave arises from an increase in conductance while the depolarizing wave was shown to arise from a decrease in conductance. The data presented indicate that both effects produced by the type A photoreceptors in ipsilateral hair cells are synaptic.", "contents": "A dual synaptic effect on hair cells in Hermissenda. Type A photorecptors can produce an initial hyperpolarizing wave followed by a delayed long-lasting increase in firing which is usually accompanied by a small depolarizing wave. The initial hyperpolarizing wave arises from an increase in conductance while the depolarizing wave was shown to arise from a decrease in conductance. The data presented indicate that both effects produced by the type A photoreceptors in ipsilateral hair cells are synaptic."} {"id": "PMID:163892", "title": "Study of sensitivity to curare in certain neurological disorders using a regional technique.", "content": "A regional technique for the study of curare sensitivity has been applied to patients with Duchenne type muscular dystrophy, myotonic disorders, certain lower motor neurone disorders, to patients with weakness in the arm after hemiplegia, to patients with hyper-reflexia and hypertonia without weakness, and to Parkinsonism. In the dystrophy patients, sensitivity to curare differs from normal controls in that the neuromuscular block persists. The possibilities that this latent defect of neuromuscular transmission is the result of acetylcholine deficiency due to a prejunctional defect or the result of alterations in the property of the postjunctional membrane are discussed. In the myotonic and lower motor neurone disorders, curare sensitivity was similar to that of normal controls. After hemiplegia, the affected side shows resistance to curare when compared with the unaffected side. In states of hyper-reflexia and hypertonia, however, the sensitivity to curare is greater than in normal controls. In Parkinsonism, sensitivity is similar to that of the controls. The results in upper motor neurone lesions are discussed in relation to the dependence of neuromuscular transmission upon the motor neurone, which, in turn, is dependent upon descending impulses.", "contents": "Study of sensitivity to curare in certain neurological disorders using a regional technique. A regional technique for the study of curare sensitivity has been applied to patients with Duchenne type muscular dystrophy, myotonic disorders, certain lower motor neurone disorders, to patients with weakness in the arm after hemiplegia, to patients with hyper-reflexia and hypertonia without weakness, and to Parkinsonism. In the dystrophy patients, sensitivity to curare differs from normal controls in that the neuromuscular block persists. The possibilities that this latent defect of neuromuscular transmission is the result of acetylcholine deficiency due to a prejunctional defect or the result of alterations in the property of the postjunctional membrane are discussed. In the myotonic and lower motor neurone disorders, curare sensitivity was similar to that of normal controls. After hemiplegia, the affected side shows resistance to curare when compared with the unaffected side. In states of hyper-reflexia and hypertonia, however, the sensitivity to curare is greater than in normal controls. In Parkinsonism, sensitivity is similar to that of the controls. The results in upper motor neurone lesions are discussed in relation to the dependence of neuromuscular transmission upon the motor neurone, which, in turn, is dependent upon descending impulses."} {"id": "PMID:163893", "title": "Disturbances in the voluntary recruitment order of anterior tibial motor units in ataxia.", "content": "The recruitment order of motor units was studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies of normal subjects that the recruitment order in sustained voluntary contraction is predominantly stable, and that motor units which increase slowly in discharge rate with increasing contraction strength and which already attain regular discharge intervals at low frequencies are always recruited before motor units which increase more rapidly in discharge rate and which do not attain regular discharge intervals until at higher frequencies. In this study 15 patients with severe cerebellar ataxia were examined. It was shown that the recruitment order in sustained voluntary contraction in attaxia is unstable and that low- and high-frequency motor units may alternate as the unit of lowest threshold.", "contents": "Disturbances in the voluntary recruitment order of anterior tibial motor units in ataxia. The recruitment order of motor units was studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies of normal subjects that the recruitment order in sustained voluntary contraction is predominantly stable, and that motor units which increase slowly in discharge rate with increasing contraction strength and which already attain regular discharge intervals at low frequencies are always recruited before motor units which increase more rapidly in discharge rate and which do not attain regular discharge intervals until at higher frequencies. In this study 15 patients with severe cerebellar ataxia were examined. It was shown that the recruitment order in sustained voluntary contraction in attaxia is unstable and that low- and high-frequency motor units may alternate as the unit of lowest threshold."} {"id": "PMID:163894", "title": "Adrenocortical insufficiency and diffuse cerebral sclerosis. Problems of presentation and diagnosis.", "content": "Three cases of adrenocortical insufficiency with diffuse cerebral sclerosis are described. One, which was confirmed by brain biopsy, had a family history of the combined disorder affecting members of a previous generation; this has not been previously reported; however pathological confirmation of the diagnosis in the earlier cases was not available. Two cases presented as acute neurosurgical emergencies and attention is drawn to this mode of presentation. Problems of aetiology, presentation and diagnosis are discussed and the finding of normal basal steroid levels is stressed.", "contents": "Adrenocortical insufficiency and diffuse cerebral sclerosis. Problems of presentation and diagnosis. Three cases of adrenocortical insufficiency with diffuse cerebral sclerosis are described. One, which was confirmed by brain biopsy, had a family history of the combined disorder affecting members of a previous generation; this has not been previously reported; however pathological confirmation of the diagnosis in the earlier cases was not available. Two cases presented as acute neurosurgical emergencies and attention is drawn to this mode of presentation. Problems of aetiology, presentation and diagnosis are discussed and the finding of normal basal steroid levels is stressed."} {"id": "PMID:163895", "title": "Establishment of continuous multiple sclerosis brain cultures after transformation with PML-SV40 virus.", "content": "PML-SV40 virus was used to transform cells from explants and monolayer subcultures of human brain derived from biopsies or autopsies of MS cases, as well as from 1 case of Jakob-Creutzfeldt disease (JC), 1 case of amyotrophic lateral sclerosis (ALS) and several cases without CNS disease. The success of transformation depended on the growth condition of the culture at the time of infection but at present at least 14 cell lines, 10 derived from MS, 2 from JC, 1 from ALS and 1 from a normal non-CNS patient are maintained in continuous culture.", "contents": "Establishment of continuous multiple sclerosis brain cultures after transformation with PML-SV40 virus. PML-SV40 virus was used to transform cells from explants and monolayer subcultures of human brain derived from biopsies or autopsies of MS cases, as well as from 1 case of Jakob-Creutzfeldt disease (JC), 1 case of amyotrophic lateral sclerosis (ALS) and several cases without CNS disease. The success of transformation depended on the growth condition of the culture at the time of infection but at present at least 14 cell lines, 10 derived from MS, 2 from JC, 1 from ALS and 1 from a normal non-CNS patient are maintained in continuous culture."} {"id": "PMID:163896", "title": "Zebra body myopathy. Clinical, histochemical and ultrastructural studies.", "content": "Clinical, electrophysiological and histological evidence is presented of a myopathy not previously described. The patient, aged 15 years, was generally weak and wasted. His condition probably began in utero, but abnormalities of the serum CPK and EMG did not become evident until adolescence. Wide variation in fibre diameter, vacuolation, calcification, increased endomysial connective tissue and intra-fibre splitting were prominent in muscle biopsy sections. Electron microscopy showed numerous rod bodies, fibre disorganisation with loss of Z-bands and occasional honeycomb structures. Frequent zebra bodies were present. Because of the large number of zebra bodies seen, the name \"zebra body myopathy\" is provisionally proposed.", "contents": "Zebra body myopathy. Clinical, histochemical and ultrastructural studies. Clinical, electrophysiological and histological evidence is presented of a myopathy not previously described. The patient, aged 15 years, was generally weak and wasted. His condition probably began in utero, but abnormalities of the serum CPK and EMG did not become evident until adolescence. Wide variation in fibre diameter, vacuolation, calcification, increased endomysial connective tissue and intra-fibre splitting were prominent in muscle biopsy sections. Electron microscopy showed numerous rod bodies, fibre disorganisation with loss of Z-bands and occasional honeycomb structures. Frequent zebra bodies were present. Because of the large number of zebra bodies seen, the name \"zebra body myopathy\" is provisionally proposed."} {"id": "PMID:163897", "title": "Experimental intracerebral movement of electron microscopic tracers of various molecular sizes.", "content": "The authors demonstrate that, while the intracerebral movement of proteins and other relatively large molecules is restricted by tight junctions of endothelia and epithelia of the brain, calcium ion penetrates these barriers and moves between the blood and CSF cavities by extracellular pathways. Mechanisms underlying CSF formation are considered on the basis of this anatomical continuity of the vascular, extracellular, and CSF compartments of the brain for very small molecules.", "contents": "Experimental intracerebral movement of electron microscopic tracers of various molecular sizes. The authors demonstrate that, while the intracerebral movement of proteins and other relatively large molecules is restricted by tight junctions of endothelia and epithelia of the brain, calcium ion penetrates these barriers and moves between the blood and CSF cavities by extracellular pathways. Mechanisms underlying CSF formation are considered on the basis of this anatomical continuity of the vascular, extracellular, and CSF compartments of the brain for very small molecules."} {"id": "PMID:163898", "title": "Differentiation of Entamoeba: a new medium and optimal conditions for axenic encystation of E. invadens.", "content": "Nutritional and culturing requirements for efficient axenic encystation of Entamoeba invadens have been studied. A simple and reliable axenic encystation medium has been developed. It contains 0.5% tryptic digest of casein, 0.5% yeast extract, and 5% dialyzed serum in 5 mM potassium phosphate, pH 7.0. Mass encystation (avg 70%) occurred within 30 hr when axenically growing trophozoites of E. invadens IP-l were transferred to this medium before they entered stationary growth phase. Mass encystation of E. invadens PZ occurred similarly, but less reproducibly. Two E. histolytica strains did not encyst. Experiments established that differentiation did not depend upon changes in the external environment after amebase were transferred to encystation medium and, therefore, was initiated by the shift from growth to encystation medium.", "contents": "Differentiation of Entamoeba: a new medium and optimal conditions for axenic encystation of E. invadens. Nutritional and culturing requirements for efficient axenic encystation of Entamoeba invadens have been studied. A simple and reliable axenic encystation medium has been developed. It contains 0.5% tryptic digest of casein, 0.5% yeast extract, and 5% dialyzed serum in 5 mM potassium phosphate, pH 7.0. Mass encystation (avg 70%) occurred within 30 hr when axenically growing trophozoites of E. invadens IP-l were transferred to this medium before they entered stationary growth phase. Mass encystation of E. invadens PZ occurred similarly, but less reproducibly. Two E. histolytica strains did not encyst. Experiments established that differentiation did not depend upon changes in the external environment after amebase were transferred to encystation medium and, therefore, was initiated by the shift from growth to encystation medium."} {"id": "PMID:163899", "title": "Cholelithiasis and ileal pathology in childhood.", "content": "Primary cholelithiasis is rare in childhood. A particular etiology has appeared over the last few years in connection with unusual physiological situations. Three cases of cholelithiasis after ileal atresia or resection are presented in children of 1, 1, and 7 yr. Another case is presented after abdominal irradiation for Wilms' tumor and ileal resection in a child of 7. The pathogenesis is discussed, raising the question of the interruption of the enterohepatic circulation of bile salts.", "contents": "Cholelithiasis and ileal pathology in childhood. Primary cholelithiasis is rare in childhood. A particular etiology has appeared over the last few years in connection with unusual physiological situations. Three cases of cholelithiasis after ileal atresia or resection are presented in children of 1, 1, and 7 yr. Another case is presented after abdominal irradiation for Wilms' tumor and ileal resection in a child of 7. The pathogenesis is discussed, raising the question of the interruption of the enterohepatic circulation of bile salts."} {"id": "PMID:163900", "title": "Islet cell tumors in childhood.", "content": "Islet cell tumors in children are briefly reviewed. Three of the total of 53 children reported in the literature are described in detail. Special emphasis is directed to localization of the tumor by angiography. The difficulties of localizing the tumor in neonates is discussed. Treatment consists in excision of the insulinoma or, if it is not possible to localize the tumor, in subtotal or total pancreatectomy.", "contents": "Islet cell tumors in childhood. Islet cell tumors in children are briefly reviewed. Three of the total of 53 children reported in the literature are described in detail. Special emphasis is directed to localization of the tumor by angiography. The difficulties of localizing the tumor in neonates is discussed. Treatment consists in excision of the insulinoma or, if it is not possible to localize the tumor, in subtotal or total pancreatectomy."} {"id": "PMID:163901", "title": "Wilms' tumor in seven children with congenital aniridia.", "content": "This report reviews our experience with 26 infants and children who demonstrate the syndrome of congenital aniridia. Twenty patients exhibited congenital sporadic aniridia, and unilateral Wilms' tumor has developed in seven of them. Six of the total of 26 patients had familial aniridia and none has shown evidence of the development of a Wilms' tumor or any other malignant tumor to date. Fraumeni studied 15 patients with congenital sporadic aniridia. Five developed Wilms' tumors. In the combined series of 35 patients with congenital sporadic aniridia, 12 patients have developed Wilms' tumor for an incidence of 34%. A brief review of our experience and a suggested protocol for the evaluation of patients with congenital aniridia is presented.", "contents": "Wilms' tumor in seven children with congenital aniridia. This report reviews our experience with 26 infants and children who demonstrate the syndrome of congenital aniridia. Twenty patients exhibited congenital sporadic aniridia, and unilateral Wilms' tumor has developed in seven of them. Six of the total of 26 patients had familial aniridia and none has shown evidence of the development of a Wilms' tumor or any other malignant tumor to date. Fraumeni studied 15 patients with congenital sporadic aniridia. Five developed Wilms' tumors. In the combined series of 35 patients with congenital sporadic aniridia, 12 patients have developed Wilms' tumor for an incidence of 34%. A brief review of our experience and a suggested protocol for the evaluation of patients with congenital aniridia is presented."} {"id": "PMID:163902", "title": "Studies of herpes simplex virus and interferon in human gingival cell cultures.", "content": "Cultures of human gingival fibroblast cells from patients with a positive or negative history of recurrent herpes simplex virus (HSV) infection were compared with respect to susceptibility to HSV infection and interferon activity. There was a possible inverse relationship between interferon sensitivity of gingival fibroblast cells and a clinical history of recurrent disease. No correlation was found between prior infection and other parameters of interferon activity or susceptibility of the cells to HSV.", "contents": "Studies of herpes simplex virus and interferon in human gingival cell cultures. Cultures of human gingival fibroblast cells from patients with a positive or negative history of recurrent herpes simplex virus (HSV) infection were compared with respect to susceptibility to HSV infection and interferon activity. There was a possible inverse relationship between interferon sensitivity of gingival fibroblast cells and a clinical history of recurrent disease. No correlation was found between prior infection and other parameters of interferon activity or susceptibility of the cells to HSV."} {"id": "PMID:163903", "title": "Presence of nonoxidative enzymes of the pentose phosphate shunt in Tetrahymena.", "content": "Tetrahymena pyriformis, strain HSM, do not have glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but contain transaldolase, transketolase, ribose 5-phosphate isomerase, ribulose-5-phosphate 3-epimerase, and ribokinase. The nonoxidative enzymes of the pentose phosphate shunt function in metabolism as indicated by the incorporation of label from [1-14C]ribose into CO2 and glycogen and by the increase in total glycogen content of cultures supplemented with ribose.", "contents": "Presence of nonoxidative enzymes of the pentose phosphate shunt in Tetrahymena. Tetrahymena pyriformis, strain HSM, do not have glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but contain transaldolase, transketolase, ribose 5-phosphate isomerase, ribulose-5-phosphate 3-epimerase, and ribokinase. The nonoxidative enzymes of the pentose phosphate shunt function in metabolism as indicated by the incorporation of label from [1-14C]ribose into CO2 and glycogen and by the increase in total glycogen content of cultures supplemented with ribose."} {"id": "PMID:163904", "title": "Effects of ACTH on the uterine weight response to HCG in mice.", "content": "The effects of ACTH and dexamethasone on the uterine weight of immature mice treated with HCG or oestradiol-17 beta were studied. The animals were treated daily for 3 days and wet and dry uterine weights were measured on the 4th day. Low doses of ACTH (1-25 mug/day) raised the sensitivity of the uterine weight response to threshold doses of HCG (0-05 to 0-1 i.u.). By increasing the doses of ACTH or HCG, the stimulation gradually turned into inhibition. By itself, ACTH was ineffective and it had no influence on the increase in uterine weight induced by oestradiol-17 beta. Dexamethasone failed to stimulate the effect of HCG.", "contents": "Effects of ACTH on the uterine weight response to HCG in mice. The effects of ACTH and dexamethasone on the uterine weight of immature mice treated with HCG or oestradiol-17 beta were studied. The animals were treated daily for 3 days and wet and dry uterine weights were measured on the 4th day. Low doses of ACTH (1-25 mug/day) raised the sensitivity of the uterine weight response to threshold doses of HCG (0-05 to 0-1 i.u.). By increasing the doses of ACTH or HCG, the stimulation gradually turned into inhibition. By itself, ACTH was ineffective and it had no influence on the increase in uterine weight induced by oestradiol-17 beta. Dexamethasone failed to stimulate the effect of HCG."} {"id": "PMID:163905", "title": "Prolonged antioestrogenic activity of ICI 46, 474 in the ovariectomized mouse.", "content": "Subcutaneous administration of ICI 46,474 (3 mg) to ovariectomized mice was found to produce vaginal refractoriness to subcutaneously administered oestradiol for up to 6 weeks. Tritiated oestradiol-17 beta accumulated in the uterus and vagina of the ovariectomized mouse, with maximum accumulation at 3 to 4 hr. This property of the target tissues was used to investigate the binding of tritiated oestradiol after the administration of 3 mg ICI 46,474 to ovariectomized mice. Radioactivity in the vagina was found to be comparable to control values 6 weeks after ICI 46,474 administration; uterine levels of radioactivity returned to control values by 10 weeks. Administration of ICI 46,474 had an oestrogenic effect upon the mouse uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or to bind oestradiol.", "contents": "Prolonged antioestrogenic activity of ICI 46, 474 in the ovariectomized mouse. Subcutaneous administration of ICI 46,474 (3 mg) to ovariectomized mice was found to produce vaginal refractoriness to subcutaneously administered oestradiol for up to 6 weeks. Tritiated oestradiol-17 beta accumulated in the uterus and vagina of the ovariectomized mouse, with maximum accumulation at 3 to 4 hr. This property of the target tissues was used to investigate the binding of tritiated oestradiol after the administration of 3 mg ICI 46,474 to ovariectomized mice. Radioactivity in the vagina was found to be comparable to control values 6 weeks after ICI 46,474 administration; uterine levels of radioactivity returned to control values by 10 weeks. Administration of ICI 46,474 had an oestrogenic effect upon the mouse uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or to bind oestradiol."} {"id": "PMID:163906", "title": "Effects of glucose starvation on normal and rous sarcoma virus-transformed chick cells.", "content": "We studied the effect of glucose starvation on glucose uptake and thymidine uptake and incorporation in cultures of normal chicken embryo cells and those transformed by Rous sarcoma virus. Resting normal fibroblasts increased the rate of glucose transport up to tenfold when they were starved for glucose, whereas fast-growing normal cells doubled the rate of uptake after starvation. Transformed cells did not show any change in the rate of glucose uptake during starvation. Thymidine uptake and incorporation by normal and transformed cells were not affected by glucose starvation. These results showed that a decrease in the glucose concentration of the medium induced a specific increase in the rate of glucose transport by normal chick fibroblasts, but did not change the transport of glucose by transformed cells. Therefore, it is suggested that glucose or one of its metabolic products regulated the hexose uptake of normal chick fibroblasts. Virus-transformed cells were insensitive to this regulation.", "contents": "Effects of glucose starvation on normal and rous sarcoma virus-transformed chick cells. We studied the effect of glucose starvation on glucose uptake and thymidine uptake and incorporation in cultures of normal chicken embryo cells and those transformed by Rous sarcoma virus. Resting normal fibroblasts increased the rate of glucose transport up to tenfold when they were starved for glucose, whereas fast-growing normal cells doubled the rate of uptake after starvation. Transformed cells did not show any change in the rate of glucose uptake during starvation. Thymidine uptake and incorporation by normal and transformed cells were not affected by glucose starvation. These results showed that a decrease in the glucose concentration of the medium induced a specific increase in the rate of glucose transport by normal chick fibroblasts, but did not change the transport of glucose by transformed cells. Therefore, it is suggested that glucose or one of its metabolic products regulated the hexose uptake of normal chick fibroblasts. Virus-transformed cells were insensitive to this regulation."} {"id": "PMID:163911", "title": "Translation of individual species of vesicular stomatitis viral mRNA.", "content": "Vesicular stomatitis virus mRNAs from three of the four bands fractionated by polyacrylamide gel electrophoresis in 99% formamide have been eluted from gels and translated in the Krebs II ascites cell-free system. Band 2 mRNA (0.7 times 10-6 daltons) directed the synthesis of the protein moiety of the glycoprotein (G), and band 3 (0.55 times 10-6 daltons) coded for the nucleocapsid (N) protein. Band 4 mRNA (o.28 times 10-6 daltons) directed the synthesis of the NS and matrix (M) proteins. The authenticity of viral proteins synthesized in vitro was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analysis of (35-S)metionine-labeled tryptic peptides. These results are consistent with the complexity analysis and coding capacities for the vesicular stomatitis virus mRNA species presented in the accompanying paper.", "contents": "Translation of individual species of vesicular stomatitis viral mRNA. Vesicular stomatitis virus mRNAs from three of the four bands fractionated by polyacrylamide gel electrophoresis in 99% formamide have been eluted from gels and translated in the Krebs II ascites cell-free system. Band 2 mRNA (0.7 times 10-6 daltons) directed the synthesis of the protein moiety of the glycoprotein (G), and band 3 (0.55 times 10-6 daltons) coded for the nucleocapsid (N) protein. Band 4 mRNA (o.28 times 10-6 daltons) directed the synthesis of the NS and matrix (M) proteins. The authenticity of viral proteins synthesized in vitro was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analysis of (35-S)metionine-labeled tryptic peptides. These results are consistent with the complexity analysis and coding capacities for the vesicular stomatitis virus mRNA species presented in the accompanying paper."} {"id": "PMID:163912", "title": "Translation and identification of the viral mRNA species isolated from subcellular fractions of vesicular stomatitis virus-infected cells.", "content": "The cytoplasm of vesicular stomatitis virus (VSV)-infected BHK cells has been separated into a fraction containing the membrane-bound polysomes and the remaining supernatant fraction. Total poly(A)-containing RNA was isolated from each fraction and purified. A 17S class of VSV mRNA was found associated almost exclusively with the membrane-bound polysomes, whereas 14,5S and 12S RNAs were found mostly in the postmembrane cytoplasmic supernatant. Poly(A)-containing VSV RNA synthesized in vitro by purified virus was resolved into the same size classes. The individual RNA fractions isolated from VSV-infected cells or synthesized in vitro were translated in cell-free extracts of wheat germ, and their polypeptide products were compared by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The corresponding in vivo and in vitro RNA fractions qualitatively direct the synthesis of the same viral polypeptides and therefore appear to contain the same mRNA species. By tryptic peptide analysis of their translation products, the in vivo VSV mRNA species have been identified. The 17S RNA, which is compartmentalized on membrane-bound polysomes, codes for a protein of molecular weight 63,000 (P-63) which is most probably a nonglycosylated form of the viral glycoprotein, G. Of the viral RNA species present in the remaining cytoplasmic supernatant, the 14.5S RNA codes almost exclusively for the N protein, whereas the 12S RNA codes predominantly for both the NS and M proteins of the virion.", "contents": "Translation and identification of the viral mRNA species isolated from subcellular fractions of vesicular stomatitis virus-infected cells. The cytoplasm of vesicular stomatitis virus (VSV)-infected BHK cells has been separated into a fraction containing the membrane-bound polysomes and the remaining supernatant fraction. Total poly(A)-containing RNA was isolated from each fraction and purified. A 17S class of VSV mRNA was found associated almost exclusively with the membrane-bound polysomes, whereas 14,5S and 12S RNAs were found mostly in the postmembrane cytoplasmic supernatant. Poly(A)-containing VSV RNA synthesized in vitro by purified virus was resolved into the same size classes. The individual RNA fractions isolated from VSV-infected cells or synthesized in vitro were translated in cell-free extracts of wheat germ, and their polypeptide products were compared by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The corresponding in vivo and in vitro RNA fractions qualitatively direct the synthesis of the same viral polypeptides and therefore appear to contain the same mRNA species. By tryptic peptide analysis of their translation products, the in vivo VSV mRNA species have been identified. The 17S RNA, which is compartmentalized on membrane-bound polysomes, codes for a protein of molecular weight 63,000 (P-63) which is most probably a nonglycosylated form of the viral glycoprotein, G. Of the viral RNA species present in the remaining cytoplasmic supernatant, the 14.5S RNA codes almost exclusively for the N protein, whereas the 12S RNA codes predominantly for both the NS and M proteins of the virion."} {"id": "PMID:163913", "title": "Mosquito cells infected with vesicular stomatitis virus yield unsialylated virions of low infectivity.", "content": "Vesicular stomatitis virus propagated in and released from Aedes albopictus cells had the normal complement of viral proteins; the glycoprotein contained carbohydrate but no sialic acid. These virions had markedly reduced hemagglutinating activity and exhibited a very high ratio of physical particles to infectious virus. In vitro sialylation of vesicular stomatitis virions grown in mosquito cells resulted in a 100-fold increase in both infectivity and hemagglutination titers to levels approaching those of virus grown in BHK-21 cells. These experiments provide an example of host-controlled modification of viral infectivity.", "contents": "Mosquito cells infected with vesicular stomatitis virus yield unsialylated virions of low infectivity. Vesicular stomatitis virus propagated in and released from Aedes albopictus cells had the normal complement of viral proteins; the glycoprotein contained carbohydrate but no sialic acid. These virions had markedly reduced hemagglutinating activity and exhibited a very high ratio of physical particles to infectious virus. In vitro sialylation of vesicular stomatitis virions grown in mosquito cells resulted in a 100-fold increase in both infectivity and hemagglutination titers to levels approaching those of virus grown in BHK-21 cells. These experiments provide an example of host-controlled modification of viral infectivity."} {"id": "PMID:163914", "title": "Host-dependent restriction of mengovirus replication. IV. Effect of some quaternary ammonium ions on the restricted replication of mengovirus in Madin-Darby bovine kidney cells.", "content": "The quaternary ammonium ions, choline, hexamethonium, and tetraethylammonium, partially reliev the restricted replication of mengovirus in Madin-Darby bovine kidney cells.", "contents": "Host-dependent restriction of mengovirus replication. IV. Effect of some quaternary ammonium ions on the restricted replication of mengovirus in Madin-Darby bovine kidney cells. The quaternary ammonium ions, choline, hexamethonium, and tetraethylammonium, partially reliev the restricted replication of mengovirus in Madin-Darby bovine kidney cells."} {"id": "PMID:163915", "title": "Influenza virion RNA-dependent RNA polymerase: stimulation by guanosine and related compounds.", "content": "The activity of RNA-dependent RNA polymerase of several influenza viruses is stimulated by guanosine. Depending upon the virus strain used, the stimulation of initial reaction rate is up to 10-fold. 5'-GMP, 3',5'-cyclic GMP, and 5'-GDP show lesser stimulation effects. No other nucleosides of 5'-NMPs stimulate, but the dinucleoside monophosphates GpG and GpC show large stimulations. We present evidence that the stimulation represents preferential initiation of genome complementary RNA chains with guanosine: (i) [3-H] guanosine is incorporated specifically at the 5'terminus of RNA in polymerase reaction mixes in vitro. (ii) This incorporation reaction has several properties similar to those of the virion polymerase elongation reaction. (iii) RNA made in the stimulated reaction behaves as complementary RNA in annealing kinetic studies, as does RNA labeled with [3-H]guanosine.", "contents": "Influenza virion RNA-dependent RNA polymerase: stimulation by guanosine and related compounds. The activity of RNA-dependent RNA polymerase of several influenza viruses is stimulated by guanosine. Depending upon the virus strain used, the stimulation of initial reaction rate is up to 10-fold. 5'-GMP, 3',5'-cyclic GMP, and 5'-GDP show lesser stimulation effects. No other nucleosides of 5'-NMPs stimulate, but the dinucleoside monophosphates GpG and GpC show large stimulations. We present evidence that the stimulation represents preferential initiation of genome complementary RNA chains with guanosine: (i) [3-H] guanosine is incorporated specifically at the 5'terminus of RNA in polymerase reaction mixes in vitro. (ii) This incorporation reaction has several properties similar to those of the virion polymerase elongation reaction. (iii) RNA made in the stimulated reaction behaves as complementary RNA in annealing kinetic studies, as does RNA labeled with [3-H]guanosine."} {"id": "PMID:163916", "title": "RNA synthesis in cells infected with herpes simplex virus. X. Properties of viral symmetric transcripts and of double-stranded RNA prepared from them.", "content": "HEp-2 cells infected with herpes simplex 1 virus contain RNA transcripts capable of forming double-stranded (DS) RNA on annealing. The properties of purified DS RNA were as follows (i) DS RNA is resistant to depolymerization by RNase A or T-1 in 2 times 0.15 M NaCl, plus 0.015 M sodium citrate (SSC) but not 0.1 times SSC or following thermal denaturation. (ii) The Tm of the viral DS RNA was 100 C in 0.1 times SSC. (iii) Undenatured DS RNA does not hybridize with viral DNA: upon denaturation, excess unlabeled RNA drove 50 to 55% of labeled DNA into DNA-RNA hybrid. The kinetics of hybridization indicate that the DS RNA consists of at least two populations of transcripts arising from 29 and 26% of viral DNA and differing 40-fold in molar concentration.", "contents": "RNA synthesis in cells infected with herpes simplex virus. X. Properties of viral symmetric transcripts and of double-stranded RNA prepared from them. HEp-2 cells infected with herpes simplex 1 virus contain RNA transcripts capable of forming double-stranded (DS) RNA on annealing. The properties of purified DS RNA were as follows (i) DS RNA is resistant to depolymerization by RNase A or T-1 in 2 times 0.15 M NaCl, plus 0.015 M sodium citrate (SSC) but not 0.1 times SSC or following thermal denaturation. (ii) The Tm of the viral DS RNA was 100 C in 0.1 times SSC. (iii) Undenatured DS RNA does not hybridize with viral DNA: upon denaturation, excess unlabeled RNA drove 50 to 55% of labeled DNA into DNA-RNA hybrid. The kinetics of hybridization indicate that the DS RNA consists of at least two populations of transcripts arising from 29 and 26% of viral DNA and differing 40-fold in molar concentration."} {"id": "PMID:163917", "title": "Structure and function of herpesvirus genomes. I. comparison of five HSV-1 and two HSV-2 strains by cleavage their DNA with eco R I restriction endonuclease.", "content": "The restriction endonuclease Eco R I cleaves HSV-1 and HSV-2 DNA into specific fragments that can be resolved by agarose gel electrophoresis. Comparison of HSV-1 strains KOS, 14-012, MP, F, and CI 101, and HSV-2 strains 333 and 186, suggests that the DNAs from type 1 strains are similar but not identical, and that the type 2 strains differ greatly from type 1 strains. The molecular lengths of the fragments have been determined by electron microscopy and can be used to calibrate gel electrophoretic analyses of DNA fragments.", "contents": "Structure and function of herpesvirus genomes. I. comparison of five HSV-1 and two HSV-2 strains by cleavage their DNA with eco R I restriction endonuclease. The restriction endonuclease Eco R I cleaves HSV-1 and HSV-2 DNA into specific fragments that can be resolved by agarose gel electrophoresis. Comparison of HSV-1 strains KOS, 14-012, MP, F, and CI 101, and HSV-2 strains 333 and 186, suggests that the DNAs from type 1 strains are similar but not identical, and that the type 2 strains differ greatly from type 1 strains. The molecular lengths of the fragments have been determined by electron microscopy and can be used to calibrate gel electrophoretic analyses of DNA fragments."} {"id": "PMID:163918", "title": "In vitro polyoma DNA synthesis: inhibition by 1-beta-d-arabinofuranosyl CTP.", "content": "The effects of 1-beta-D-arabinofuranosyl CTP (ara-CTP) on DNA replication were studied in an in vitro system from polyoma-infected BALB/3T3 cells. Ara-CTP concentrations of larger than or equal to 150 muM were found to block in vitro DNA synthesis completely, and concentrations of smaller than or equal to 0.3 muM had no inhibitory effect. Intermediate concentrations resulted in a concentration-dependent reduction of the in vitro synthesis rate. Long-term labeling with [alpha-32-P]ara-CTP demonstrated the incorporation of the analogue into cellular and viral DNA concomitantly with [3-H]TTP. In pulse-labeling experiments, at noninhibitory concentrations of the analogue, ara-CTP was incorporated into short DNA fragments and long growing strands to relatively the same extent as TTP. Partial venom phosphodiesterase digestion liberated the incoporated are-CTP at essentially the same rate as incorporated TTP, excluding a predominantly terminal incorporation, and after total venom phosphodiesterase digestion greater than 80% of the incorporated ara-CTP was recovered as 5'-ara-CMP. Analysis of the long-term in vitro viral DNA product made in the presence of partially inhibiting ara-CTP concentrations demonstrated that none of the steps leading to mature viral DNA were totally inhibited at the ara-CTP concentrations used. Pulse labeling of replicating viral DNA in the presence of ara-CTP revealed two consistent differences in the pattern found in control pulses: (i) predominant labeling of short chains (5S) with reduced amounts of radioactivity in the longer growing viral DNA strands (smaller than or equal to 16S), and (ii) a one-third to one-half reduction in size for short DNA chains labeled in the presence of ara-CTP. Release of the ara-CTP inhibition with excess dCTP resulted in covalent extension of these smaller short chans to approximately the size of regular short chains labeled in the absence of the inhibitor. Isolated short chains synthesized in the presence of ara-CTP exhibited a slightly lower degree of self-complementarity than regular short chains. The predominant labeling of short chains during pulses is, therefore, not a consequence of discontinuous growth on both sides of the replication fork. Similar results were obtained with ara-ATP and N-ethylmaleimide. The experiments indicate that ara-CTP acts primarily on DNA-polymerizing activities, affecting different DNA polymerases to varying degrees. The results are discussed in terms of the possible number and identity of polymerases involved in viral (and cellular) DNA replication.", "contents": "In vitro polyoma DNA synthesis: inhibition by 1-beta-d-arabinofuranosyl CTP. The effects of 1-beta-D-arabinofuranosyl CTP (ara-CTP) on DNA replication were studied in an in vitro system from polyoma-infected BALB/3T3 cells. Ara-CTP concentrations of larger than or equal to 150 muM were found to block in vitro DNA synthesis completely, and concentrations of smaller than or equal to 0.3 muM had no inhibitory effect. Intermediate concentrations resulted in a concentration-dependent reduction of the in vitro synthesis rate. Long-term labeling with [alpha-32-P]ara-CTP demonstrated the incorporation of the analogue into cellular and viral DNA concomitantly with [3-H]TTP. In pulse-labeling experiments, at noninhibitory concentrations of the analogue, ara-CTP was incorporated into short DNA fragments and long growing strands to relatively the same extent as TTP. Partial venom phosphodiesterase digestion liberated the incoporated are-CTP at essentially the same rate as incorporated TTP, excluding a predominantly terminal incorporation, and after total venom phosphodiesterase digestion greater than 80% of the incorporated ara-CTP was recovered as 5'-ara-CMP. Analysis of the long-term in vitro viral DNA product made in the presence of partially inhibiting ara-CTP concentrations demonstrated that none of the steps leading to mature viral DNA were totally inhibited at the ara-CTP concentrations used. Pulse labeling of replicating viral DNA in the presence of ara-CTP revealed two consistent differences in the pattern found in control pulses: (i) predominant labeling of short chains (5S) with reduced amounts of radioactivity in the longer growing viral DNA strands (smaller than or equal to 16S), and (ii) a one-third to one-half reduction in size for short DNA chains labeled in the presence of ara-CTP. Release of the ara-CTP inhibition with excess dCTP resulted in covalent extension of these smaller short chans to approximately the size of regular short chains labeled in the absence of the inhibitor. Isolated short chains synthesized in the presence of ara-CTP exhibited a slightly lower degree of self-complementarity than regular short chains. The predominant labeling of short chains during pulses is, therefore, not a consequence of discontinuous growth on both sides of the replication fork. Similar results were obtained with ara-ATP and N-ethylmaleimide. The experiments indicate that ara-CTP acts primarily on DNA-polymerizing activities, affecting different DNA polymerases to varying degrees. The results are discussed in terms of the possible number and identity of polymerases involved in viral (and cellular) DNA replication."} {"id": "PMID:163919", "title": "Nongenetic complementation of group V temperature-sensitive mutants of vesicular stomatitis virus by UV-irradiated virus.", "content": "Cells infected with temperature-sensitive (ts) mutants of complementation group V of vesicular stomatitis virus (VSV) give an enhanced yield at nonpermissive temperature when co-infected or superinfected with UV-irradiated virus. Virions produced in these mixed infections are temperature sensitive and do not complement ts V45. Rescue of group V mutants is multiplicity dependent. It can occur in the presence of cycloheximide; kinetics of rescue are similar in the absence or in the presence of the drug. Rescue is due to nongenetic complementation and is interpreted as a trigger effect on maturation of a small quantity of biologically active protein V molecules provided by UV-irradiated virus. These results are comfirmed by rescue of ts V45 by UV-irradiated, defective, interferring T particles.", "contents": "Nongenetic complementation of group V temperature-sensitive mutants of vesicular stomatitis virus by UV-irradiated virus. Cells infected with temperature-sensitive (ts) mutants of complementation group V of vesicular stomatitis virus (VSV) give an enhanced yield at nonpermissive temperature when co-infected or superinfected with UV-irradiated virus. Virions produced in these mixed infections are temperature sensitive and do not complement ts V45. Rescue of group V mutants is multiplicity dependent. It can occur in the presence of cycloheximide; kinetics of rescue are similar in the absence or in the presence of the drug. Rescue is due to nongenetic complementation and is interpreted as a trigger effect on maturation of a small quantity of biologically active protein V molecules provided by UV-irradiated virus. These results are comfirmed by rescue of ts V45 by UV-irradiated, defective, interferring T particles."} {"id": "PMID:163920", "title": "Temperature-sensitive host range mutants of herpes simplex virus type 2.", "content": "Herpesviruses are capable of several types of infection of a host cell. To investigate the early events which ultimately determine the nature of the virus-host cell interaction, a system was established utilizing temperature-sensitive mutants of herpes simplex virus type 2. Four mutants have been isolated which fail to induce cytopathic effects and do not replicate at 39 C in hamster embryo fibroblast cells. At least one mutant is virus DNA negative. Since intracellular complementation is detectable between pairs of mutants, a virus function is known to be temperature sensitive. However, all four mutants induce cytopathic effects and replicate to parental virus levels in rabbit kidney cells at 39 C. This suggests that a host cell function, lacking or nonfunctional in HEF cells but present in rabbit kidney cells at 39 C, is required for the replication of these mutants in hamster embryo fibroblasts cells at 39 C. Therefore, we conclude that these mutants are both temperature sensitive and exhibit host range properties.", "contents": "Temperature-sensitive host range mutants of herpes simplex virus type 2. Herpesviruses are capable of several types of infection of a host cell. To investigate the early events which ultimately determine the nature of the virus-host cell interaction, a system was established utilizing temperature-sensitive mutants of herpes simplex virus type 2. Four mutants have been isolated which fail to induce cytopathic effects and do not replicate at 39 C in hamster embryo fibroblast cells. At least one mutant is virus DNA negative. Since intracellular complementation is detectable between pairs of mutants, a virus function is known to be temperature sensitive. However, all four mutants induce cytopathic effects and replicate to parental virus levels in rabbit kidney cells at 39 C. This suggests that a host cell function, lacking or nonfunctional in HEF cells but present in rabbit kidney cells at 39 C, is required for the replication of these mutants in hamster embryo fibroblasts cells at 39 C. Therefore, we conclude that these mutants are both temperature sensitive and exhibit host range properties."} {"id": "PMID:163921", "title": "Virion polypeptide composition of the human papovavirus BK: comparison with simian virus 40 and polyoma virus.", "content": "The polypeptide composition of labeled BK virus was compared with that of simian virus 40 (SV40) and polyoma virus by co-electrophoresis of disrupted virions in polyacrylamide gels containing approximately 73% of the capsid protein and had a molecular weight of 39,000. It was smaller than VP1 of SV40 and polyoma virus. The other polypeptides of BK virus were similar in molecular weight to those of SV40. A comparison of the proteins of BK virus and SV40 iodinated with chloramine T before and after disruption in alkaline buffer at pH 10.5 revealed differences between the two viruses in the number and distribution of tyrosines available for iodination. The tryptic peptides of VP1, VP3, VP4, and VP5 combined of SV40 were compared with those of the same polypeptides of BK virus. Among the 19 peptides of VP1 resolved, only two were common to both viruses. The analyses of VP4 and VP5, the histone-like proteins, however, showed more similarity between the viruses, with 6 of 15 resolved peptides in common. The tryptic digests of VP3 were completely different.", "contents": "Virion polypeptide composition of the human papovavirus BK: comparison with simian virus 40 and polyoma virus. The polypeptide composition of labeled BK virus was compared with that of simian virus 40 (SV40) and polyoma virus by co-electrophoresis of disrupted virions in polyacrylamide gels containing approximately 73% of the capsid protein and had a molecular weight of 39,000. It was smaller than VP1 of SV40 and polyoma virus. The other polypeptides of BK virus were similar in molecular weight to those of SV40. A comparison of the proteins of BK virus and SV40 iodinated with chloramine T before and after disruption in alkaline buffer at pH 10.5 revealed differences between the two viruses in the number and distribution of tyrosines available for iodination. The tryptic peptides of VP1, VP3, VP4, and VP5 combined of SV40 were compared with those of the same polypeptides of BK virus. Among the 19 peptides of VP1 resolved, only two were common to both viruses. The analyses of VP4 and VP5, the histone-like proteins, however, showed more similarity between the viruses, with 6 of 15 resolved peptides in common. The tryptic digests of VP3 were completely different."} {"id": "PMID:163922", "title": "RNA metabolism of murine leukemia virus II. Endogenous virus-specific RNA in the uninfected BALB/c cell line JLS-V9.", "content": "Type C virus-specific RNA sequences of BALB/c endogenous virus were detected in JLS-V9 cells (an uninfected BALB/c derived line) by annealing cell RNA with 3-H-labeled virus-specific DNA. Endogenous viruses used in preparing the 3-H-labeled DNA (mostly xenotropic) was prepared from JLS-V9 cells induced to produce virus with iododeoxyuridine. In whole-cell extracts, two virus-specific RNA species, 38S and 27S, were detected. No 60 to 70S virus-specific RNA was found. The same two species of virus-specific RNA were observed in isolated cytoplasmic RNA and in cytoplasmic RNA selected for polyadenylic acid-containing species by binding and elution from oligo(dT) cellulose. Very little, if any, of the virus-specific RNA was active as messenger RNA on polyribosomes. No virus-specific RNA transcribed from genes coding for the BALB/c endogenous N-tropic virus was detected, since 3-H-labeled DNA prepared from endogenous N-tropic virus did not hybridize measurably with JLS-V9 RNA.", "contents": "RNA metabolism of murine leukemia virus II. Endogenous virus-specific RNA in the uninfected BALB/c cell line JLS-V9. Type C virus-specific RNA sequences of BALB/c endogenous virus were detected in JLS-V9 cells (an uninfected BALB/c derived line) by annealing cell RNA with 3-H-labeled virus-specific DNA. Endogenous viruses used in preparing the 3-H-labeled DNA (mostly xenotropic) was prepared from JLS-V9 cells induced to produce virus with iododeoxyuridine. In whole-cell extracts, two virus-specific RNA species, 38S and 27S, were detected. No 60 to 70S virus-specific RNA was found. The same two species of virus-specific RNA were observed in isolated cytoplasmic RNA and in cytoplasmic RNA selected for polyadenylic acid-containing species by binding and elution from oligo(dT) cellulose. Very little, if any, of the virus-specific RNA was active as messenger RNA on polyribosomes. No virus-specific RNA transcribed from genes coding for the BALB/c endogenous N-tropic virus was detected, since 3-H-labeled DNA prepared from endogenous N-tropic virus did not hybridize measurably with JLS-V9 RNA."} {"id": "PMID:163923", "title": "Host-dependent restriction of mengovirus replication. II. Effect of host restriction on late viral RNA synthesis and viral maturation.", "content": "Restricted mengovirus replication in Mandin-Darby bovine kidney (MDBK) cells is characterized by a 400-fold reduction in infectious virus yield and a 40-fold increase in the production of noninfectious virus. Using conditions which insure that all MDBK cells are infected, virus-specific RNA and protein synthesis were measured in the restrictive host and in a permissive host for mengovirus, HeLa cells. Labeling kinetics and sucrose gradient analysis of mengovirus-specific RNA from MDBK cells show a reduction of 10-fold in virion RNA, 5-fold in double-stranded RNA, and 12.5-fold in single-stranded RNA. The viral RNA biosynthetic processes which occur late in the replicative cycle and result in the production of 90% of the single-stranded viral RNA that is packaged into capsid proteins in the permissive host are absent in restrictive MDBK cells. Viral protein synthesis as measured by labeled viral-specific polysome is decreased, and there is an accumulation of 80S subviral particles in the restricted host. It is suggested that restriction may act at a number of stages of viral replication and maturation.", "contents": "Host-dependent restriction of mengovirus replication. II. Effect of host restriction on late viral RNA synthesis and viral maturation. Restricted mengovirus replication in Mandin-Darby bovine kidney (MDBK) cells is characterized by a 400-fold reduction in infectious virus yield and a 40-fold increase in the production of noninfectious virus. Using conditions which insure that all MDBK cells are infected, virus-specific RNA and protein synthesis were measured in the restrictive host and in a permissive host for mengovirus, HeLa cells. Labeling kinetics and sucrose gradient analysis of mengovirus-specific RNA from MDBK cells show a reduction of 10-fold in virion RNA, 5-fold in double-stranded RNA, and 12.5-fold in single-stranded RNA. The viral RNA biosynthetic processes which occur late in the replicative cycle and result in the production of 90% of the single-stranded viral RNA that is packaged into capsid proteins in the permissive host are absent in restrictive MDBK cells. Viral protein synthesis as measured by labeled viral-specific polysome is decreased, and there is an accumulation of 80S subviral particles in the restricted host. It is suggested that restriction may act at a number of stages of viral replication and maturation."} {"id": "PMID:163924", "title": "Cellular adsorption function of the sialoglycoprotein of vesicular stomatitis virus and its neuraminic acid.", "content": "Exposure of vesicular stomatitis (VS) virions to neuraminidase resulted in loss of their ability to agglutinate goose erythrocytes and to attach to L cells concomitant with hydrolysis of sialic acid. These viral adsorptive functions were also destroyed by tryspsinization. Sialyl transferase resialylation in vitro of neuraminidase-treated VS virions restored their hamagglutinating and adsorptive functions almost to original levels. Erythrocyte and L cell receptors for attachment of VS virions were blocked by fully sialylated fetuin and by VS viral sialoglycopeptides. Smaller VS viral glycopeptides generated by extensive trypsinization were less effective inhibitors of hemagglutination than were larger glycopeptides; neuraminic acid and neuraminosyl lactose had no capacity to inhibit hamagglutination or adsorption of virus to L cells. These data suggest that cellular receptors for viral adsorption recognize sialoglycopeptides of a certain size. Neuraminidase desialylation did not significantly alter the isoelectric point of VS virions. Cells exposed to DEAE-dextran, trypsin, or neuraminidase showed significantly increased capacity to attach fully sialylated but not desialylated VS virions. Neuraminidase desialylation of L cells, Chinese hamster ovary cells, and Madin-Darby bovine kidney cells resulted in enhanced susceptibility to plaque formation by VS virus.", "contents": "Cellular adsorption function of the sialoglycoprotein of vesicular stomatitis virus and its neuraminic acid. Exposure of vesicular stomatitis (VS) virions to neuraminidase resulted in loss of their ability to agglutinate goose erythrocytes and to attach to L cells concomitant with hydrolysis of sialic acid. These viral adsorptive functions were also destroyed by tryspsinization. Sialyl transferase resialylation in vitro of neuraminidase-treated VS virions restored their hamagglutinating and adsorptive functions almost to original levels. Erythrocyte and L cell receptors for attachment of VS virions were blocked by fully sialylated fetuin and by VS viral sialoglycopeptides. Smaller VS viral glycopeptides generated by extensive trypsinization were less effective inhibitors of hemagglutination than were larger glycopeptides; neuraminic acid and neuraminosyl lactose had no capacity to inhibit hamagglutination or adsorption of virus to L cells. These data suggest that cellular receptors for viral adsorption recognize sialoglycopeptides of a certain size. Neuraminidase desialylation did not significantly alter the isoelectric point of VS virions. Cells exposed to DEAE-dextran, trypsin, or neuraminidase showed significantly increased capacity to attach fully sialylated but not desialylated VS virions. Neuraminidase desialylation of L cells, Chinese hamster ovary cells, and Madin-Darby bovine kidney cells resulted in enhanced susceptibility to plaque formation by VS virus."} {"id": "PMID:163925", "title": "Isolation of two subgroup-specific leukemogenic viruses from standard avian myeloblastosis virus.", "content": "Two populations of virus having subgroup-specific homogeneity (A and B) were isolated from standard avian myeloblastosis virus stocks by passage in vivo through genetically defined chickens. Each possesses leukemogenic activity in vivo. Other properties and potential usefulness of these agents are discussed.", "contents": "Isolation of two subgroup-specific leukemogenic viruses from standard avian myeloblastosis virus. Two populations of virus having subgroup-specific homogeneity (A and B) were isolated from standard avian myeloblastosis virus stocks by passage in vivo through genetically defined chickens. Each possesses leukemogenic activity in vivo. Other properties and potential usefulness of these agents are discussed."} {"id": "PMID:163926", "title": "Identification of a viral protein involved in post-translational maturation of the encephalomyocarditis virus capsid precursor.", "content": "Translation of encephalomyocarditis virus RNA in a cell-free system from uninfected Krebs ascites cells results in the synthesis of a major polypeptide product with a molecular weight of approximately 112,000. In contrast, when the viral RNA is translated in a cell-free system from virus-infected cells, this polypeptide is absent and the largest polypeptide produced has a molecular weight of about 100,000. This latter polypeptide comigrates on sodium dodecyl sulfate-gels with in vivo virus capsid precursor A, and the two have identical patterns of CNBr-generated peptides. A polypeptide having a molecular weight of 12,500 is also a major translation product in the system from infected cells (but not from uninfected cells). This polypeptide appears to be generated by cleavage of the NH-2-terminal portion of the viral RNA-dependent polypeptides by a proteolytic activity present in the infected cell-free system. This proteolytic activity copurifies with the 23,000-molecular weight viral capsid protein gamma, found in infected cells, through chromatography on DEAE-cellulose and cellulose phosphate. This suggests that gamma is itself a proteolytic enzyme involved in maturation of the viral capsid precursor.", "contents": "Identification of a viral protein involved in post-translational maturation of the encephalomyocarditis virus capsid precursor. Translation of encephalomyocarditis virus RNA in a cell-free system from uninfected Krebs ascites cells results in the synthesis of a major polypeptide product with a molecular weight of approximately 112,000. In contrast, when the viral RNA is translated in a cell-free system from virus-infected cells, this polypeptide is absent and the largest polypeptide produced has a molecular weight of about 100,000. This latter polypeptide comigrates on sodium dodecyl sulfate-gels with in vivo virus capsid precursor A, and the two have identical patterns of CNBr-generated peptides. A polypeptide having a molecular weight of 12,500 is also a major translation product in the system from infected cells (but not from uninfected cells). This polypeptide appears to be generated by cleavage of the NH-2-terminal portion of the viral RNA-dependent polypeptides by a proteolytic activity present in the infected cell-free system. This proteolytic activity copurifies with the 23,000-molecular weight viral capsid protein gamma, found in infected cells, through chromatography on DEAE-cellulose and cellulose phosphate. This suggests that gamma is itself a proteolytic enzyme involved in maturation of the viral capsid precursor."} {"id": "PMID:163927", "title": "Physical map of polyoma viral DNA fragments produced by cleavage with a restriction enzyme from Haemophilus aegyptius, endonuclease R-HaeIII.", "content": "Digestion of polyoma viral DNA with a restriction enzyme from Haemophilus aegyptius generates at least 22 unique fragments. The fragments have been characterized with respect to size and physical order on the polyoma genome, and the 5' to 3' orientation of the (+) and (-) strands has been determined. A method for specific radiolabeling of adjacent fragments was employed to establish the fragment order. This technique may be useful for ordering the fragments produced by digestion of complex DNAs.", "contents": "Physical map of polyoma viral DNA fragments produced by cleavage with a restriction enzyme from Haemophilus aegyptius, endonuclease R-HaeIII. Digestion of polyoma viral DNA with a restriction enzyme from Haemophilus aegyptius generates at least 22 unique fragments. The fragments have been characterized with respect to size and physical order on the polyoma genome, and the 5' to 3' orientation of the (+) and (-) strands has been determined. A method for specific radiolabeling of adjacent fragments was employed to establish the fragment order. This technique may be useful for ordering the fragments produced by digestion of complex DNAs."} {"id": "PMID:163928", "title": "Nucleotide sequence complexities, molecular weights, and poly(A) content of the vesicular stomatitis virus mRNA species.", "content": "Poly(A)-containing vesicular stomatitis virus mRNA species synthesized in vesicular stomatitis virus-infected cells have been separated into four bands by electrophoresis on formamide-polyacrylamide gels. Two-dimensional fingerprints of ribonuclease T-1 and ribonuclease A digests of the RNA from each band show that they contain unique oligonucleotide sequences as well as 60 to 125 nucleotides of poly(A). The fingerprints were used to determine the nucleotide sequence complexities of RNA from three of the bands. Two contain nucleotide sequences which account completely for their molecular weights (0.70 times 10-6 and 0.55 times 10-6) determined by gel electrophoresis and sedimentation rate, and, therefore, these are radiochemically pure RNA species. The most rapidly migrating band must contain two ro three different RNA species since it has a molecular weight of 0.28 times 10-6, determined by physical methods, and a nucleotide sequence complexity two to three times that expected for a pure RNA species of this size. These data are in complete accord with translational studies (accompanying paper) which show that each of the two pure RNA species codes for a distinct viral protein, whereas the third codes for two viral proteins. From the molecular weight and sequence complexity determinations on mRNA from the bands, we conclude that most of the vesicular stomatitis virus genome is transcribed into discrete mRNA species.", "contents": "Nucleotide sequence complexities, molecular weights, and poly(A) content of the vesicular stomatitis virus mRNA species. Poly(A)-containing vesicular stomatitis virus mRNA species synthesized in vesicular stomatitis virus-infected cells have been separated into four bands by electrophoresis on formamide-polyacrylamide gels. Two-dimensional fingerprints of ribonuclease T-1 and ribonuclease A digests of the RNA from each band show that they contain unique oligonucleotide sequences as well as 60 to 125 nucleotides of poly(A). The fingerprints were used to determine the nucleotide sequence complexities of RNA from three of the bands. Two contain nucleotide sequences which account completely for their molecular weights (0.70 times 10-6 and 0.55 times 10-6) determined by gel electrophoresis and sedimentation rate, and, therefore, these are radiochemically pure RNA species. The most rapidly migrating band must contain two ro three different RNA species since it has a molecular weight of 0.28 times 10-6, determined by physical methods, and a nucleotide sequence complexity two to three times that expected for a pure RNA species of this size. These data are in complete accord with translational studies (accompanying paper) which show that each of the two pure RNA species codes for a distinct viral protein, whereas the third codes for two viral proteins. From the molecular weight and sequence complexity determinations on mRNA from the bands, we conclude that most of the vesicular stomatitis virus genome is transcribed into discrete mRNA species."} {"id": "PMID:163929", "title": "Correlation of pre-treatment serum 17-hydroxycorticosteroid values with survival in patients with prostatic cancer.", "content": "Total 17-OHCS values were determined before and after treatment in 715 patients with all stages of prostatic cancer. The pre-treatment 17-OHCS level was an important variable in predicting survival and appeared to be a better prognostic indicator of death in the first year than the patient's age, treatment or stage of disease. Generally, the higher the initial value of serum 17-OHCS the greater the probability of death in the first year of treatment. There was no preponderance of one type of death over another when patients with initial high and low values were compared.", "contents": "Correlation of pre-treatment serum 17-hydroxycorticosteroid values with survival in patients with prostatic cancer. Total 17-OHCS values were determined before and after treatment in 715 patients with all stages of prostatic cancer. The pre-treatment 17-OHCS level was an important variable in predicting survival and appeared to be a better prognostic indicator of death in the first year than the patient's age, treatment or stage of disease. Generally, the higher the initial value of serum 17-OHCS the greater the probability of death in the first year of treatment. There was no preponderance of one type of death over another when patients with initial high and low values were compared."} {"id": "PMID:163931", "title": "Increased virus shedding with aspirin treatment of rhinovirus infection.", "content": "In two double-blind trials, volunteers challenged with rhinovirus were treated with aspirin or placebo. Aspirin treatment did not alter the rates of infection or illness but was associated with a moderate reduction in the frequency or severity of some symptoms. The overall benefit in rhinovirus infection was not statistically significant. Aspirin treatment appeared to cause a highly significant increase in the rate of virus shedding in treated subjects. The increase in virus shedding must be considered an adverse event that could influence the course of the disease in the individual and increase the likelihood of the spread of the infection to contacts.", "contents": "Increased virus shedding with aspirin treatment of rhinovirus infection. In two double-blind trials, volunteers challenged with rhinovirus were treated with aspirin or placebo. Aspirin treatment did not alter the rates of infection or illness but was associated with a moderate reduction in the frequency or severity of some symptoms. The overall benefit in rhinovirus infection was not statistically significant. Aspirin treatment appeared to cause a highly significant increase in the rate of virus shedding in treated subjects. The increase in virus shedding must be considered an adverse event that could influence the course of the disease in the individual and increase the likelihood of the spread of the infection to contacts."} {"id": "PMID:163932", "title": "Are chlamydial infections the most prevalent venereal disease?", "content": "We studied two population groups (more than 1,600 patients) to determine the prevalence and clinical associations of genital tract infections with chlamydiae and herpesviruses. Base-line isolation rates for asymptomatic women having routine pelvic examinations were much lower than rates for symptomatic women. In both groups, chlamydiae were more prevalent than herpesviruses. Chlamydial infection was associated much more commonly with cervicitis (36.6%) than with vaginitis only (4.1%). Among 282 symptomatic men, the cultures of 19.9% yielded chlamydiae, and 4.3%, herpesviruses. Chlamydiae were recovered from 35.5% (27 of 76) of specimens from men with nongonococcal urethritis, and from an even larger proportion, 57% (24 of 42), of the specimens from men with frank discharge.", "contents": "Are chlamydial infections the most prevalent venereal disease? We studied two population groups (more than 1,600 patients) to determine the prevalence and clinical associations of genital tract infections with chlamydiae and herpesviruses. Base-line isolation rates for asymptomatic women having routine pelvic examinations were much lower than rates for symptomatic women. In both groups, chlamydiae were more prevalent than herpesviruses. Chlamydial infection was associated much more commonly with cervicitis (36.6%) than with vaginitis only (4.1%). Among 282 symptomatic men, the cultures of 19.9% yielded chlamydiae, and 4.3%, herpesviruses. Chlamydiae were recovered from 35.5% (27 of 76) of specimens from men with nongonococcal urethritis, and from an even larger proportion, 57% (24 of 42), of the specimens from men with frank discharge."} {"id": "PMID:163933", "title": "Hyperlipidemia in cerebrovascular diseases.", "content": "1. Hypertriglyceridemia and hyper beta-lipoproteinemia are closely related to the pathophysiologic status of the cerebrovascular patients. 2. The electrophoretic analysis of serum lipoprotein is the usefull method for the study on hyperlipidemia in the cerebrovascular disease. 3. The electrophoretic analysis of the serum lipoprotein gives close relation to the clinical features in the patients with normal serum lipid levels as well as in those with the hyperlipidemia. 4. Hyperlipidemia relates closely to the renal impairment, which is supposed to originate from the sclerotic changes of renal artery.", "contents": "Hyperlipidemia in cerebrovascular diseases. 1. Hypertriglyceridemia and hyper beta-lipoproteinemia are closely related to the pathophysiologic status of the cerebrovascular patients. 2. The electrophoretic analysis of serum lipoprotein is the usefull method for the study on hyperlipidemia in the cerebrovascular disease. 3. The electrophoretic analysis of the serum lipoprotein gives close relation to the clinical features in the patients with normal serum lipid levels as well as in those with the hyperlipidemia. 4. Hyperlipidemia relates closely to the renal impairment, which is supposed to originate from the sclerotic changes of renal artery."} {"id": "PMID:163934", "title": "Ischemic heart disease and hyperlipidemia.", "content": "Studies on lipid and lipoprotein abnormalities which are associable with ischemic heart disease were presented. None of the subjects studied for this report had clinical signs or symptoms characteristic to \"familial or sporadic\" hyperlipoproteinemia. Only few showed gross abnormalities in lipid chemistries which are compatible with these clinical entities. Lipid abnormalities characteristic to the majority of ischemic heart patients were modest to moderate increase of serum total and free cholesterol and triglyceride; either independent increase or combined increase of these lipid fractions. Determination of free cholesterol may favor to detect such minute abnormality in modest hyperlipidemia as seen in ischemic heart patients. As expressed by our lipoprotein PAG electrophoresis pattern, B and Bp pattern (Fig. 1) seemed to be important lipoprotein abnormalities because of high incidence of ischemic heart disease (60 to 65%). Another feature of these hyperbeta lipoproteinemic state without (B pattern) or with (Bp pattern) moderate prebeta lipoprotein is highly suggestive of premature onset of ischemic heart suggestive premature onset of ischemic heart disease in the subjects with these lipoprotein patterns. Pb battern (hyperpre-beta lipoproteinemic state) was the next, because of frequent occurrence of this pattern (approx. 30%) among the cardiovascular patients and relatively high incidence (approx. 40%) of ischemic heart disease. PB pattern (combine hyperpre-beta and hyperbeta lipoproteinemic state) occurred rarely but incidence of ischemic heart disease in the subject with this pattern was high (approx. 40%). Midband lipoprotein which is one of the unique lipoprotein species detected by PAG electrophoresis may possibly reflect disordered lipoprotein metabolism. However, its association with ischemic heart disease seemed highly unlikely. However, further studies on this and other unusual lipoproteins detectable with PAG electrophoresis seems productive. Extensive studies on cine coronary angiographically established subjects (well characterized study subjects) with this new method in addition to the others would be highly productive to obtain more reliable conclusion on this subject, and hence, to obtain more effective guide line for early identification or for prevention of coronary atherosclerosis.", "contents": "Ischemic heart disease and hyperlipidemia. Studies on lipid and lipoprotein abnormalities which are associable with ischemic heart disease were presented. None of the subjects studied for this report had clinical signs or symptoms characteristic to \"familial or sporadic\" hyperlipoproteinemia. Only few showed gross abnormalities in lipid chemistries which are compatible with these clinical entities. Lipid abnormalities characteristic to the majority of ischemic heart patients were modest to moderate increase of serum total and free cholesterol and triglyceride; either independent increase or combined increase of these lipid fractions. Determination of free cholesterol may favor to detect such minute abnormality in modest hyperlipidemia as seen in ischemic heart patients. As expressed by our lipoprotein PAG electrophoresis pattern, B and Bp pattern (Fig. 1) seemed to be important lipoprotein abnormalities because of high incidence of ischemic heart disease (60 to 65%). Another feature of these hyperbeta lipoproteinemic state without (B pattern) or with (Bp pattern) moderate prebeta lipoprotein is highly suggestive of premature onset of ischemic heart suggestive premature onset of ischemic heart disease in the subjects with these lipoprotein patterns. Pb battern (hyperpre-beta lipoproteinemic state) was the next, because of frequent occurrence of this pattern (approx. 30%) among the cardiovascular patients and relatively high incidence (approx. 40%) of ischemic heart disease. PB pattern (combine hyperpre-beta and hyperbeta lipoproteinemic state) occurred rarely but incidence of ischemic heart disease in the subject with this pattern was high (approx. 40%). Midband lipoprotein which is one of the unique lipoprotein species detected by PAG electrophoresis may possibly reflect disordered lipoprotein metabolism. However, its association with ischemic heart disease seemed highly unlikely. However, further studies on this and other unusual lipoproteins detectable with PAG electrophoresis seems productive. Extensive studies on cine coronary angiographically established subjects (well characterized study subjects) with this new method in addition to the others would be highly productive to obtain more reliable conclusion on this subject, and hence, to obtain more effective guide line for early identification or for prevention of coronary atherosclerosis."} {"id": "PMID:163935", "title": "Characteristics of serum lipid and lipoprotein patterns in patients with coronary sclerosis and with the slightest hyperlipidemia.", "content": "1. Serum lipid and lipoprotein patterns of subjects with/without coronary sclerosis and having less than 300 mg/100 ml of serum total cholesterol were analyzed. Subjects woth coronary sclerosis were classified into 2 groups, myocardial infarction (MI) group and coronary sclerosis (CS) group, in accordance with the criteria for the diagnosis of coronary sclerosis established by the special study group of the Educational Ministry in 1960. 2. While serum total cholesterol was higher in the MI group than in the other groups, there was no difference in total cholesterol concentration between the CS group and the control. However, the concentration of free cholesterol, triglycerides, total phospholipids and total lipids increased in the control, the CS and the MI group in this order. 3. The percent concentration of pre-beta and beta and the ratio of beta/alpha and pre-beta+beta/alpha increased in the control, the CS and the MI group in this order. Type IIb hyperlipoproteinemia was observed more frequently in the MI group than in the control one. Type IIa and IV hyperlipoproteinemia did not change into any other phenotypes, but Type IIb changed occationally into Type IIa. 4. So called extra pre-beta lipoprotein was observed more frequently in the CS and MI groups than in the control one. 5. These results suggested that even slight changes in serum lipid and lipoprotein patterns might be related to atherogenecity.", "contents": "Characteristics of serum lipid and lipoprotein patterns in patients with coronary sclerosis and with the slightest hyperlipidemia. 1. Serum lipid and lipoprotein patterns of subjects with/without coronary sclerosis and having less than 300 mg/100 ml of serum total cholesterol were analyzed. Subjects woth coronary sclerosis were classified into 2 groups, myocardial infarction (MI) group and coronary sclerosis (CS) group, in accordance with the criteria for the diagnosis of coronary sclerosis established by the special study group of the Educational Ministry in 1960. 2. While serum total cholesterol was higher in the MI group than in the other groups, there was no difference in total cholesterol concentration between the CS group and the control. However, the concentration of free cholesterol, triglycerides, total phospholipids and total lipids increased in the control, the CS and the MI group in this order. 3. The percent concentration of pre-beta and beta and the ratio of beta/alpha and pre-beta+beta/alpha increased in the control, the CS and the MI group in this order. Type IIb hyperlipoproteinemia was observed more frequently in the MI group than in the control one. Type IIa and IV hyperlipoproteinemia did not change into any other phenotypes, but Type IIb changed occationally into Type IIa. 4. So called extra pre-beta lipoprotein was observed more frequently in the CS and MI groups than in the control one. 5. These results suggested that even slight changes in serum lipid and lipoprotein patterns might be related to atherogenecity."} {"id": "PMID:163936", "title": "Lipoproteins and hyperlipidemia; special refference on the LCAT and apo-lipoproteins.", "content": "1) HDL3 is the most excellent substrate of LCAT reaction. 2) Significant relationships of LCAT activities with serum concentrations of LDL, VLDL, cholesterol, triglyceride and phospholipid, and body weight were observed. No significant relationships were observed between the activity and serum concentrations of HDL3 and HDL2. 3) LCAT activities increased in the various secondary hyperlipedemic states. However, the activities remained within normal range in the familial hyperlipidemias. 4) Immunological properties of apolipoproteins were consistent between normal and hyperlipidemic subjects. 5) Amino acid compositions of hyperlipidemic subjects were almost consistent with those of normal subjects. However, significant differences of amino acid compositions were observed in the patients with familial type II and type IV hyperlipidemias with genetic factor, as compaired with those of normal and other hyperlipidemic subjects. 6) Discussions were made about the above-mentioned results. Authors greatly acknowledge Drs. T. Shimizu, M. Iijima, E. Sasa, T. Kinoshita and M. Harada for their cooperations.", "contents": "Lipoproteins and hyperlipidemia; special refference on the LCAT and apo-lipoproteins. 1) HDL3 is the most excellent substrate of LCAT reaction. 2) Significant relationships of LCAT activities with serum concentrations of LDL, VLDL, cholesterol, triglyceride and phospholipid, and body weight were observed. No significant relationships were observed between the activity and serum concentrations of HDL3 and HDL2. 3) LCAT activities increased in the various secondary hyperlipedemic states. However, the activities remained within normal range in the familial hyperlipidemias. 4) Immunological properties of apolipoproteins were consistent between normal and hyperlipidemic subjects. 5) Amino acid compositions of hyperlipidemic subjects were almost consistent with those of normal subjects. However, significant differences of amino acid compositions were observed in the patients with familial type II and type IV hyperlipidemias with genetic factor, as compaired with those of normal and other hyperlipidemic subjects. 6) Discussions were made about the above-mentioned results. Authors greatly acknowledge Drs. T. Shimizu, M. Iijima, E. Sasa, T. Kinoshita and M. Harada for their cooperations."} {"id": "PMID:163937", "title": "[Epidemic keratoconjunctivitis: a report on a clinical epidemic (author's transl)].", "content": "After description of the clinical and serological features of an epidemic keratoconjunctivitis caused by adeno-virus (Type 8) the author compares results of 4 methods of treatment. The schedule consisted of \"Okuzell-Coldan\" eye drops as placebo, eye drops of corticosteroid content, intramuscular inoculation with Interferonogen and a combined treatment with 0.3 percent \"Neutralrot\" eye drops and radiation with daylight lamp HPR 125 W produced by Philips Co. Ltd. The transition from the conjunctival form to the keratic form could be best prevented through the last named therapy.", "contents": "[Epidemic keratoconjunctivitis: a report on a clinical epidemic (author's transl)]. After description of the clinical and serological features of an epidemic keratoconjunctivitis caused by adeno-virus (Type 8) the author compares results of 4 methods of treatment. The schedule consisted of \"Okuzell-Coldan\" eye drops as placebo, eye drops of corticosteroid content, intramuscular inoculation with Interferonogen and a combined treatment with 0.3 percent \"Neutralrot\" eye drops and radiation with daylight lamp HPR 125 W produced by Philips Co. Ltd. The transition from the conjunctival form to the keratic form could be best prevented through the last named therapy."} {"id": "PMID:163938", "title": "[Treatment of epidemic keratoconjunctivitis with ABOB. Clinical and laboratory investigations (author's transl)].", "content": "In an epidemic of viral keratoconjunctivitis in Bulgaria in 1972, caused by adenovirus 9, we applied ABOB in 1 percent solution topically in 120 of all 151 observed patients. When the treatment could be begun in first 3-5 days of the disease, a very favourable curing effect was noted. In most of the patients occurred a significant subjective improvement. The effect was most pronounced upon the course of ther keratitis stage. When ABOB was applied early, the observed keratitis was lighter, with slight visual impairment (with a duration of more than one month in 14.4 percent of the patients, as opposed to 57.3 percent in a placebo group), with quicker epithelialization of corneal erosions and, as a result, with fewer residual corneal opacities.", "contents": "[Treatment of epidemic keratoconjunctivitis with ABOB. Clinical and laboratory investigations (author's transl)]. In an epidemic of viral keratoconjunctivitis in Bulgaria in 1972, caused by adenovirus 9, we applied ABOB in 1 percent solution topically in 120 of all 151 observed patients. When the treatment could be begun in first 3-5 days of the disease, a very favourable curing effect was noted. In most of the patients occurred a significant subjective improvement. The effect was most pronounced upon the course of ther keratitis stage. When ABOB was applied early, the observed keratitis was lighter, with slight visual impairment (with a duration of more than one month in 14.4 percent of the patients, as opposed to 57.3 percent in a placebo group), with quicker epithelialization of corneal erosions and, as a result, with fewer residual corneal opacities."} {"id": "PMID:163940", "title": "Granular cell myoblastoma: another unusual esophageal lesion.", "content": "The case is presented of a 48-year-old woman with esophageal granular cell myoblastoma who was treated by local excision. A review of the literature is also included. So far as we can determine, this is the thirteenth such case reported.", "contents": "Granular cell myoblastoma: another unusual esophageal lesion. The case is presented of a 48-year-old woman with esophageal granular cell myoblastoma who was treated by local excision. A review of the literature is also included. So far as we can determine, this is the thirteenth such case reported."} {"id": "PMID:163941", "title": "Fasting serum bile acid levels in the primary hyperlipoproteinemias.", "content": "A newly developed radioimmunoassay specific for conjugates of cholic acid (CCA) was used to measure the fasting serum levels of these bile acids in 233 patients with primary hyperlipoproteinemia classified as type IIa, IIb, III, IV, or V hyperlipoproteinemia as well as in 80 healthy control subjects. Subjects with type IIa hyperlipoproteinemia had significantly lower levels of CCA (0.9 plus or minus 0.06 muM, mean plus or minus SE) than did healthy controls (0.50 plus or minus 0.08 muM). Patients with type IIb, III, IV, and V hyperlipoproteinemia had values similar to those of the control group. The abnormally low fasting value of CCA in type IIa patients is considered to reflect decreased secretion of bile acid into the intestine in such patients, who are known to have defective bile acid synthesis rates and decreased bile acid pool sizes.", "contents": "Fasting serum bile acid levels in the primary hyperlipoproteinemias. A newly developed radioimmunoassay specific for conjugates of cholic acid (CCA) was used to measure the fasting serum levels of these bile acids in 233 patients with primary hyperlipoproteinemia classified as type IIa, IIb, III, IV, or V hyperlipoproteinemia as well as in 80 healthy control subjects. Subjects with type IIa hyperlipoproteinemia had significantly lower levels of CCA (0.9 plus or minus 0.06 muM, mean plus or minus SE) than did healthy controls (0.50 plus or minus 0.08 muM). Patients with type IIb, III, IV, and V hyperlipoproteinemia had values similar to those of the control group. The abnormally low fasting value of CCA in type IIa patients is considered to reflect decreased secretion of bile acid into the intestine in such patients, who are known to have defective bile acid synthesis rates and decreased bile acid pool sizes."} {"id": "PMID:163942", "title": "Isolation of Chlamydia from patients with urethritis.", "content": "From October 1973 through August 1974, 335 genitourinary tract specimens from patients with urethritis were inoculated into McCoy's cell cultures for the diagnosis of Chlamydia infections. Of the 45 Chlamydia isolates, 42 were recovered when glass vials rather than plastic microtiter plates were used as cell culture vessels. Herpes simplex virus was isolated 15 times. Bacterial overgrowth occurred 42 times; however, in 20 specimens the contamination was not apparent until after the first subculture. This is the first report of the frequency of Chlamydia infections in patients with urethritis in the Midwest and indicates that these organisms have a significant etiologic role in nongonococcal urethritis in this community.", "contents": "Isolation of Chlamydia from patients with urethritis. From October 1973 through August 1974, 335 genitourinary tract specimens from patients with urethritis were inoculated into McCoy's cell cultures for the diagnosis of Chlamydia infections. Of the 45 Chlamydia isolates, 42 were recovered when glass vials rather than plastic microtiter plates were used as cell culture vessels. Herpes simplex virus was isolated 15 times. Bacterial overgrowth occurred 42 times; however, in 20 specimens the contamination was not apparent until after the first subculture. This is the first report of the frequency of Chlamydia infections in patients with urethritis in the Midwest and indicates that these organisms have a significant etiologic role in nongonococcal urethritis in this community."} {"id": "PMID:163943", "title": "Recent trends in chemotherapy of solid tumors.", "content": "A multidisciplinary approach consisting of surgery, radiotherapy, chemotherapy, and immunotherapy is now being used in both early and advanced stages of carcinoma. Positive and constructive approaches available today vary from adjuvant studies for early or primary disease to combinations of radiotherapy and chemotherapy for advanced disease. Methods of treatment considered to hold significant promise are discussed.", "contents": "Recent trends in chemotherapy of solid tumors. A multidisciplinary approach consisting of surgery, radiotherapy, chemotherapy, and immunotherapy is now being used in both early and advanced stages of carcinoma. Positive and constructive approaches available today vary from adjuvant studies for early or primary disease to combinations of radiotherapy and chemotherapy for advanced disease. Methods of treatment considered to hold significant promise are discussed."} {"id": "PMID:163944", "title": "Current status of regional arterial infusion chemotherapy.", "content": "The rationale for this method is that a prolonged, continuous exposure of tumor cells to an antimetabolite is required for effective antimetabolic activity to develop in the tumor cell population. Overall experience in selected sites such as head and neck, liver, and extremities is reviewed.", "contents": "Current status of regional arterial infusion chemotherapy. The rationale for this method is that a prolonged, continuous exposure of tumor cells to an antimetabolite is required for effective antimetabolic activity to develop in the tumor cell population. Overall experience in selected sites such as head and neck, liver, and extremities is reviewed."} {"id": "PMID:163945", "title": "Syndromes resulting from ectopic hormone-producing tumors.", "content": "Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors.", "contents": "Syndromes resulting from ectopic hormone-producing tumors. Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors."} {"id": "PMID:163946", "title": "Cutaneous manifestations of internal malignancy.", "content": "Skin changes may result from metastases to skin or from chemicals or hormones that are secreted by the tumor, resulting in identifiable cutaneous syndromes, or may be inflammatory dermatoses, benign or malignant proliferative lesions, or nevoid states whose association is recognized but the mechanisms of which are unexplained.", "contents": "Cutaneous manifestations of internal malignancy. Skin changes may result from metastases to skin or from chemicals or hormones that are secreted by the tumor, resulting in identifiable cutaneous syndromes, or may be inflammatory dermatoses, benign or malignant proliferative lesions, or nevoid states whose association is recognized but the mechanisms of which are unexplained."} {"id": "PMID:163947", "title": "Ifluence of dietary fatty acids on membrane properties and enzyme activities of liver mitochondria of normal and hypophysectomized rats.", "content": "Studies are reported on the effects of diets containing fatty supplements with (A) a high concentration of arachidonate (46% concentrate of ethyl arachidonate), (B) a high concentration of linoleate (corn oil), and (C) an essential fatty acid deficient, fully saturated fat (hydrogenated coconut oil) upon lipid composition, membrane permeability, and enzyme activities of liver mitochondria of normal and hypophysectomized rats. The fatty supplements produced differences in the fatty acid composition of the liver mitochondria; hypophysectomy, in addition, influenced the neutral and phospholipid composition. Permeability, indicated by swelling properties, correlated generally with the degree of unsaturation and essential fatty acid content of the lipid of the mitochondria of the normal animals. The fatty supplements also influenced the enzyme acitivites of the mitochondria of the normal animals. The mitochondria of the hypophysectomized animals were less responsive to the differences in the dietary fat in both their swelling properties and enzyme activities. Although the relationship was complex, it appeared that the hypophysis was involved in the functions of essential fatty acids in liver mitochondria.", "contents": "Ifluence of dietary fatty acids on membrane properties and enzyme activities of liver mitochondria of normal and hypophysectomized rats. Studies are reported on the effects of diets containing fatty supplements with (A) a high concentration of arachidonate (46% concentrate of ethyl arachidonate), (B) a high concentration of linoleate (corn oil), and (C) an essential fatty acid deficient, fully saturated fat (hydrogenated coconut oil) upon lipid composition, membrane permeability, and enzyme activities of liver mitochondria of normal and hypophysectomized rats. The fatty supplements produced differences in the fatty acid composition of the liver mitochondria; hypophysectomy, in addition, influenced the neutral and phospholipid composition. Permeability, indicated by swelling properties, correlated generally with the degree of unsaturation and essential fatty acid content of the lipid of the mitochondria of the normal animals. The fatty supplements also influenced the enzyme acitivites of the mitochondria of the normal animals. The mitochondria of the hypophysectomized animals were less responsive to the differences in the dietary fat in both their swelling properties and enzyme activities. Although the relationship was complex, it appeared that the hypophysis was involved in the functions of essential fatty acids in liver mitochondria."} {"id": "PMID:163949", "title": "75Se-selenomethionine-labeled lipoproteins in hyperlipidemic and normolipidemic humans.", "content": "Investigating the feasability and application appropriate to determination of lipoprotein turnover, 75Se-selenomethionine (Se-M) incorporation in lipoproteins was studied in eight hospitalized patients. Three were hyperlipidemic diabetic subjects (HL), and five were normolipidemic but otherwise abnormal subjects (NL). Maximum activity was observed in the VLDL fraction within 2-3 hr, and was followed by a biexponential decay. Incorporation into the LDL-I (density, 1.006-1.019 mug/ml) occurred at a rate which correlated with the rapid decay rate of the VLDL Se-M activity. The decay of the Se-M was single exponential in the LDL-I and LDL-II (density, 1.019-1.063 mug/ml), suggesting undirectional transfer of the label. The HDL fraction showed a rapid initial Se-M uptake which was followed by a slow rise, resulting in a complex time-activity curve. The Se-M activity was significantly higher in the VLDL fraction and slightly lower in the LDL and HDL fractions in the HL as compared to the NL subjects. The VLDL-apoprotein concentration increased by a significantly greater amount in the HL (374 mug/ml) than in the NL subjects (67 mug/ml). There was a significant increase in VLDL-apoprotein turnover in the presence of a fractional turnover rate that was not significantly lower in the three hyperlipidemic subjects compared to the NL controls. In vivo 75Se-selenomethionine labeling allows the estimation of the synthesis and removal rate of apoproteins.", "contents": "75Se-selenomethionine-labeled lipoproteins in hyperlipidemic and normolipidemic humans. Investigating the feasability and application appropriate to determination of lipoprotein turnover, 75Se-selenomethionine (Se-M) incorporation in lipoproteins was studied in eight hospitalized patients. Three were hyperlipidemic diabetic subjects (HL), and five were normolipidemic but otherwise abnormal subjects (NL). Maximum activity was observed in the VLDL fraction within 2-3 hr, and was followed by a biexponential decay. Incorporation into the LDL-I (density, 1.006-1.019 mug/ml) occurred at a rate which correlated with the rapid decay rate of the VLDL Se-M activity. The decay of the Se-M was single exponential in the LDL-I and LDL-II (density, 1.019-1.063 mug/ml), suggesting undirectional transfer of the label. The HDL fraction showed a rapid initial Se-M uptake which was followed by a slow rise, resulting in a complex time-activity curve. The Se-M activity was significantly higher in the VLDL fraction and slightly lower in the LDL and HDL fractions in the HL as compared to the NL subjects. The VLDL-apoprotein concentration increased by a significantly greater amount in the HL (374 mug/ml) than in the NL subjects (67 mug/ml). There was a significant increase in VLDL-apoprotein turnover in the presence of a fractional turnover rate that was not significantly lower in the three hyperlipidemic subjects compared to the NL controls. In vivo 75Se-selenomethionine labeling allows the estimation of the synthesis and removal rate of apoproteins."} {"id": "PMID:163950", "title": "Effects of estrogenic compounds on triglyceride kinetics.", "content": "Paired studies of triglyceride kinetics were made in 8 women on and off postmenopausal estrogen supplementation. When estrogens were discontinued, mean very-low-density lipoprotein triglyceride (VLD-TG) and VLD-TG turnover rate fell respectively from 555 to 349 mg/100 ml, and from 30-18 mg/kg/hr (p smaller than 0.01). Maximal turnover rate (Vmax) and VLD-TG concentration at 1/2 V max (Km), were 82.4 mg/kg/hr and 704.14 mg/100 ml on estrogen and fell to 41.83 and 347.51 when estrogen was discontinued (p smaller than 0.01). Estrogen supplementation did not lengthen VLD-TG half-life or diminish the fractional turnover rate of VLD-TG. Estrogens apparently increase VLD-TG by augmenting VLD-TG production rates.", "contents": "Effects of estrogenic compounds on triglyceride kinetics. Paired studies of triglyceride kinetics were made in 8 women on and off postmenopausal estrogen supplementation. When estrogens were discontinued, mean very-low-density lipoprotein triglyceride (VLD-TG) and VLD-TG turnover rate fell respectively from 555 to 349 mg/100 ml, and from 30-18 mg/kg/hr (p smaller than 0.01). Maximal turnover rate (Vmax) and VLD-TG concentration at 1/2 V max (Km), were 82.4 mg/kg/hr and 704.14 mg/100 ml on estrogen and fell to 41.83 and 347.51 when estrogen was discontinued (p smaller than 0.01). Estrogen supplementation did not lengthen VLD-TG half-life or diminish the fractional turnover rate of VLD-TG. Estrogens apparently increase VLD-TG by augmenting VLD-TG production rates."} {"id": "PMID:163957", "title": "[Globular corpuscles in hepatomas of Swiss mice].", "content": "In hapatomas formed spontaneously without cirrhosis at Swiss mice numerous globular corpuscules of eosinophil character were found. These corpuscules as revealed by electron microscopy are formed in cyternas of the rough surfaced endoplasmatic reticulum and are of the nature of protein.", "contents": "[Globular corpuscles in hepatomas of Swiss mice]. In hapatomas formed spontaneously without cirrhosis at Swiss mice numerous globular corpuscules of eosinophil character were found. These corpuscules as revealed by electron microscopy are formed in cyternas of the rough surfaced endoplasmatic reticulum and are of the nature of protein."} {"id": "PMID:163958", "title": "[Electron microscopic study of cytoplasmic crystals in liver damages caused by alcoholism].", "content": "Liver biopsy of 50 patients with liver disease of alcoholic etiology was examined electronmicroscopically. In every stage of the disease presence of intramitochondrial paracrystalloids was revealed. Hyalin of alcoholic origin of fibrillar structure was seen in cases of alcoholic hepatitis. By the electronmicroscopic examination of three cases of alcoholic fatty liver a special form of cytoplasmatic paracristalloid inclusion could be seen. This inclusion consists of membranless parallely lying fibrills. Changing the plain of the preparats containing inclusions by the aid of a goniometer the structure of the inclusions appeared in a form of \"honey-comb\". Inclusion in the question can not be regarded identical neither with intramitochondrial inclusions nor with the fibrills of the so called alcoholic hyalin. Formation and function of these inclusions are as yet unknown.", "contents": "[Electron microscopic study of cytoplasmic crystals in liver damages caused by alcoholism]. Liver biopsy of 50 patients with liver disease of alcoholic etiology was examined electronmicroscopically. In every stage of the disease presence of intramitochondrial paracrystalloids was revealed. Hyalin of alcoholic origin of fibrillar structure was seen in cases of alcoholic hepatitis. By the electronmicroscopic examination of three cases of alcoholic fatty liver a special form of cytoplasmatic paracristalloid inclusion could be seen. This inclusion consists of membranless parallely lying fibrills. Changing the plain of the preparats containing inclusions by the aid of a goniometer the structure of the inclusions appeared in a form of \"honey-comb\". Inclusion in the question can not be regarded identical neither with intramitochondrial inclusions nor with the fibrills of the so called alcoholic hyalin. Formation and function of these inclusions are as yet unknown."} {"id": "PMID:163959", "title": "Azaguanine-resistant mutants induced by several mutagens in a neurospora heterokaryon.", "content": "This paper reports the development of a new system for the detection of forward mutations in a heterokaryon of Neurospora crassa. This system, designed to detect a wide variety of genetic alterations, is based upon the detection of 8-azaguanine-resistant mutants in an adenine-requiring heterokaryon carrying the aza-3 gene. Induction of mutations in the aza-3 gene was detected after treatment of conidia with ultraviolet light, X-rays, ethyl methanesulfonate (EMS), or the acridine mustard, ICR-170. The pattern of appearance of mutant colonies and various factors in mutant selection are discussed.", "contents": "Azaguanine-resistant mutants induced by several mutagens in a neurospora heterokaryon. This paper reports the development of a new system for the detection of forward mutations in a heterokaryon of Neurospora crassa. This system, designed to detect a wide variety of genetic alterations, is based upon the detection of 8-azaguanine-resistant mutants in an adenine-requiring heterokaryon carrying the aza-3 gene. Induction of mutations in the aza-3 gene was detected after treatment of conidia with ultraviolet light, X-rays, ethyl methanesulfonate (EMS), or the acridine mustard, ICR-170. The pattern of appearance of mutant colonies and various factors in mutant selection are discussed."} {"id": "PMID:163960", "title": "A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias.", "content": "A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (less than 0.11 mg per milligram of urinary creatnine). Urinary calcium was high (greater than or equal to 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (greater than 4.60 mu moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (greater than 6.86 mu moles per gram of creatinine) or high-normal fasting urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria.", "contents": "A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias. A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (less than 0.11 mg per milligram of urinary creatnine). Urinary calcium was high (greater than or equal to 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (greater than 4.60 mu moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (greater than 6.86 mu moles per gram of creatinine) or high-normal fasting urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria."} {"id": "PMID:163964", "title": "Travelers' diarrhea and toxigenic Escherichia coli.", "content": "In a group of 133 United States students studied for 18 days after arriving in Mexico, diarrhea developed in 38 (29 per cent). Diarrhea rarely began before the fourth day, and the mean onset was 13 days after arrival. Symptoms lasted an average of 3.4 days but persisted in 21 per cent of sick students. Heat-labile enterotoxin-producing Escheria coli was found in the stools of 72 per cent of sick and 15 per cent of healthy students. None had heat-labile Esch. coli when they entered Mexico. The incubation period was short, generally 24 to 48 hours, and the carrier state was five days or less in 82 per cent of students surveyed. Entamoeba histolytica was found in 6 per cent of cases of diarrhea, but not salmonella, shigella or penetrating Esch. coli. These studies suggest that approximately 70 per cent of travelers' diarrhea in Mexico is associated with heat-labile toxigenic strains of Esch. coli.", "contents": "Travelers' diarrhea and toxigenic Escherichia coli. In a group of 133 United States students studied for 18 days after arriving in Mexico, diarrhea developed in 38 (29 per cent). Diarrhea rarely began before the fourth day, and the mean onset was 13 days after arrival. Symptoms lasted an average of 3.4 days but persisted in 21 per cent of sick students. Heat-labile enterotoxin-producing Escheria coli was found in the stools of 72 per cent of sick and 15 per cent of healthy students. None had heat-labile Esch. coli when they entered Mexico. The incubation period was short, generally 24 to 48 hours, and the carrier state was five days or less in 82 per cent of students surveyed. Entamoeba histolytica was found in 6 per cent of cases of diarrhea, but not salmonella, shigella or penetrating Esch. coli. These studies suggest that approximately 70 per cent of travelers' diarrhea in Mexico is associated with heat-labile toxigenic strains of Esch. coli."} {"id": "PMID:163965", "title": "Pancreatic cholera: benefical effects of treatment with streptozotocin.", "content": "Two patients with pancreatic cholera and islet-cell carcinoma were treated with intra-arterial streptozotocin. Before therapy, they had stool volumes from 2 to 8 liters per day and required 200 to 800 mEq per day of supplemental potassium. After three to five doses of streptozotocin (1.5 per square meter), both stool volume and number and size of hepatic metastases decreased markedly. One patient has had normally formed stools for 12 months; the other had a 90 per cent reduction in stool volume for 13 months with additional therapy. Both patients' serum potassium returned to normal without need for supplementation. Jejunal adenylate cyclase activity was normal in both, and plasma vasoactive intestinal peptide was detectable in only one. After chemotherapy, these findings showed no consistent change. Pharmacologic studies suggest that arterial administration increased either tumor or hepatic extraction (or both) of streptozotocin by two times and decreased renal exposure to this nephrotoxic drug by one third.", "contents": "Pancreatic cholera: benefical effects of treatment with streptozotocin. Two patients with pancreatic cholera and islet-cell carcinoma were treated with intra-arterial streptozotocin. Before therapy, they had stool volumes from 2 to 8 liters per day and required 200 to 800 mEq per day of supplemental potassium. After three to five doses of streptozotocin (1.5 per square meter), both stool volume and number and size of hepatic metastases decreased markedly. One patient has had normally formed stools for 12 months; the other had a 90 per cent reduction in stool volume for 13 months with additional therapy. Both patients' serum potassium returned to normal without need for supplementation. Jejunal adenylate cyclase activity was normal in both, and plasma vasoactive intestinal peptide was detectable in only one. After chemotherapy, these findings showed no consistent change. Pharmacologic studies suggest that arterial administration increased either tumor or hepatic extraction (or both) of streptozotocin by two times and decreased renal exposure to this nephrotoxic drug by one third."} {"id": "PMID:163969", "title": "17 Beta-estradiol transport and metabolism in human red blood cells.", "content": "Attempts to measure the function of red blood cells as steroid metabolizing tissue showed that the membrane plays an important role. Of the 17beta-estradiol associated with red cells, 2/3 was bound to the membrane while 1/3 was in the soluble fraction. The binding appears to be nonspecific and linearly related to the amount incubated. Binding was more extensive at 2 C than at 26 C. Successive washes of red cells with isotonic sodium chloride solution increased their ability to bind 17beta-estradiol. Red cells incubated in isotonic salt media removed 85.1 plus or minus 3.2% (SD) of the total estrogens present and this value remained within narrow limits for incubation times as short as 15 s and as long as 19 h at 37 C. When incubated in homologous plasma, only 8-12% of estrogens in the media became associated with cells. The eight-fold difference in cell binding between salt solution and plasma can be attributed to competition with plasm aproteins. Presence of plasma proteins diminished but does not prevent activity of 17beta-hydroxysteroid dehydrogenase of red cells. Cells produce four times more estrone when incubated in saline media than when incubated in their own plasma. The enzyme is in the soluble portion of the cells and the steroids have to traverse the membrane in both directions. In the transfer of estrogens from plasma of cytoplasm, the membrane needs to be considered as a separate compartment.", "contents": "17 Beta-estradiol transport and metabolism in human red blood cells. Attempts to measure the function of red blood cells as steroid metabolizing tissue showed that the membrane plays an important role. Of the 17beta-estradiol associated with red cells, 2/3 was bound to the membrane while 1/3 was in the soluble fraction. The binding appears to be nonspecific and linearly related to the amount incubated. Binding was more extensive at 2 C than at 26 C. Successive washes of red cells with isotonic sodium chloride solution increased their ability to bind 17beta-estradiol. Red cells incubated in isotonic salt media removed 85.1 plus or minus 3.2% (SD) of the total estrogens present and this value remained within narrow limits for incubation times as short as 15 s and as long as 19 h at 37 C. When incubated in homologous plasma, only 8-12% of estrogens in the media became associated with cells. The eight-fold difference in cell binding between salt solution and plasma can be attributed to competition with plasm aproteins. Presence of plasma proteins diminished but does not prevent activity of 17beta-hydroxysteroid dehydrogenase of red cells. Cells produce four times more estrone when incubated in saline media than when incubated in their own plasma. The enzyme is in the soluble portion of the cells and the steroids have to traverse the membrane in both directions. In the transfer of estrogens from plasma of cytoplasm, the membrane needs to be considered as a separate compartment."} {"id": "PMID:163970", "title": "Studies of ACTH secretion control in 116 cases of Cushing's syndrome.", "content": "Plasma ACTH (normal value: 0.16 plus or minus mU/100 ml) was measured in 116 patients with Cushing's syndrome, using a bioassay including dynamic tests and sequential determinations. In 10 patients with adrenal tumors ACTH levels were nondetectable (ND) or low, and usually nonstimulatable. In 10 patients with ectopic ACTH secretion high levels (0.42 plus or minus 0.07 mU/100 ml) were measured. The extracts of 6 tumors yielded an ACTH-like substance. Forty-three patients with Cushing's disease (without pituitary tumor) had, before treatment, a mean ACTH level of 0.18 plus or minus 0.01 mU/100 ml, accompanied by high levels of plasma cortisol (32.1 plus or minus 1.9 mug/100 ml). Irregular nycthemeral variations occurred. ACTH rose to 0.30 mU/100 ml after incomplete adrenalectomy (20 patients) and to 1.14 mU/100 ml after total adrenalectomy (21 patients). Dexamethasone (8 mg per day) suppressed ACTH levels. Metyrapone induced a normal ACTH rise, but at abnormal times. Lysine-vasopressin (LVP) induced an ACTH mean relative increase of 120% before, and of 140% after adrenalectomy (i.e., within the normal range). Six nonadrenalectomized patients with pituitary tumors showed similar abnormalities of ACTH regulation. However, the ACTH rise after LVP was above 500%. When pituitary tumors occurred after adrenalectomy (12 patients) the mean basal ACTH level was 18 mU/100 ml. Dexamethasone induced a 90% decrease, and LVP a 416% increase in ACTH levels. In 6 patients with nodular adrenal hyperplasia, ACTH was undetectable before treatment. After adrenalectomy, ACTH rose to 0.4 mU/100 ml (11 patients) and the increase after LVP was 90%. Five additional patients developed pituitary tumors. These data confirm the abnormalities of ACTH feedback regulation in Cushing's disease. However, even when pituitary tumors occur, ACTH levels can be altered by metyrapone, dexamethasone and LVP. This last test is of particular interest for the detection of pituitary tumors. The follow-up pattern of treated nodular adrenal hyperplasia appears to be very similar to that of Cushing's disease.", "contents": "Studies of ACTH secretion control in 116 cases of Cushing's syndrome. Plasma ACTH (normal value: 0.16 plus or minus mU/100 ml) was measured in 116 patients with Cushing's syndrome, using a bioassay including dynamic tests and sequential determinations. In 10 patients with adrenal tumors ACTH levels were nondetectable (ND) or low, and usually nonstimulatable. In 10 patients with ectopic ACTH secretion high levels (0.42 plus or minus 0.07 mU/100 ml) were measured. The extracts of 6 tumors yielded an ACTH-like substance. Forty-three patients with Cushing's disease (without pituitary tumor) had, before treatment, a mean ACTH level of 0.18 plus or minus 0.01 mU/100 ml, accompanied by high levels of plasma cortisol (32.1 plus or minus 1.9 mug/100 ml). Irregular nycthemeral variations occurred. ACTH rose to 0.30 mU/100 ml after incomplete adrenalectomy (20 patients) and to 1.14 mU/100 ml after total adrenalectomy (21 patients). Dexamethasone (8 mg per day) suppressed ACTH levels. Metyrapone induced a normal ACTH rise, but at abnormal times. Lysine-vasopressin (LVP) induced an ACTH mean relative increase of 120% before, and of 140% after adrenalectomy (i.e., within the normal range). Six nonadrenalectomized patients with pituitary tumors showed similar abnormalities of ACTH regulation. However, the ACTH rise after LVP was above 500%. When pituitary tumors occurred after adrenalectomy (12 patients) the mean basal ACTH level was 18 mU/100 ml. Dexamethasone induced a 90% decrease, and LVP a 416% increase in ACTH levels. In 6 patients with nodular adrenal hyperplasia, ACTH was undetectable before treatment. After adrenalectomy, ACTH rose to 0.4 mU/100 ml (11 patients) and the increase after LVP was 90%. Five additional patients developed pituitary tumors. These data confirm the abnormalities of ACTH feedback regulation in Cushing's disease. However, even when pituitary tumors occur, ACTH levels can be altered by metyrapone, dexamethasone and LVP. This last test is of particular interest for the detection of pituitary tumors. The follow-up pattern of treated nodular adrenal hyperplasia appears to be very similar to that of Cushing's disease."} {"id": "PMID:163971", "title": "Radioreceptor assay for human chorionic gonadotropin.", "content": "A sensitive radioreceptor assay capable of detecting 100 pg of human chorionic gonadotropin has been developed using ovarian receptors and (125I)hCG. The dose-response curves of a series of urine and serum samples from pregnant women were linear and parallel to standard curves of 2nd International Standard hCG and purified hCG when logit of percent bound was plotted against log dose. Potency estimates of pregnancy sera, measured by radioreceptor assays, were approximately 2 times greater than those determined by radioimmunoassays. Examination of hCG concentrations in the urine of pregnant and nonpregnant women, using a receptor assay, showed good correlation with the result obtained with a standard agglutination pregnancy test. This readioreceptor assay, which can be made as sensitive as radioimmunoassay, provides a rapid and simple method for the measurement of biologically active hCG and LH.", "contents": "Radioreceptor assay for human chorionic gonadotropin. A sensitive radioreceptor assay capable of detecting 100 pg of human chorionic gonadotropin has been developed using ovarian receptors and (125I)hCG. The dose-response curves of a series of urine and serum samples from pregnant women were linear and parallel to standard curves of 2nd International Standard hCG and purified hCG when logit of percent bound was plotted against log dose. Potency estimates of pregnancy sera, measured by radioreceptor assays, were approximately 2 times greater than those determined by radioimmunoassays. Examination of hCG concentrations in the urine of pregnant and nonpregnant women, using a receptor assay, showed good correlation with the result obtained with a standard agglutination pregnancy test. This readioreceptor assay, which can be made as sensitive as radioimmunoassay, provides a rapid and simple method for the measurement of biologically active hCG and LH."} {"id": "PMID:163972", "title": "Partial pharmacodynamic model for the circadian-episodic secretion of cortisol in man.", "content": "A pharmacodynamic model was developed to facilitate computer analysis of the circadian-episodic influx of cortisol into plasma from the adrenal gland. The model consists of a catenary system of a biorhythmic control, the adrenal gland, and a body compartment containing circulating cortisol. Computer nonlinear regression analysis was carried out on data consisting of plasma cortisol concentrations measured at 30-min intervals over 1 day in a group of normal children. Circadian rhythmic synthesis of cortisol by the adrenal gland was described by a sinusoidal function which provides the level (284 plus or minus 50 mugg/h/m2) and amplitude (245 plus or minus 50 mug/h/m2) of the synthesis rate and the period (24 hours) and acrophase (8.14 plus or minus 1.95 h) of the cycle. Cosinor analysis of the data confirmed a highly significant circadian rhythm in the daily synthesis rate of cortisol. Episodic secretion, described by an empirical switch function, is assumed to result from accumulation of small amounts of cortisol precursors in the adrenal gland and intermittent stimulation of cortisol release by ACTH. This was found to take place over 46.6 plus or minus 2.4% of a 24-h day. Circulating cortisol is contained in a single body compartment with an apparent volume of distribution (5.3 plus or minus 0.55 liters/m2) from which elimination occurs by first-order metabolic clearance. The biological half-life averaged 0.96 plus or minus 0.18 h. Upon least-square optimization of selected kinetic parameters, the circadian-episodic model increases the accountable variation (r2 x 100) to 89% in comparison with the 35% obtained by use of only a periodic function.", "contents": "Partial pharmacodynamic model for the circadian-episodic secretion of cortisol in man. A pharmacodynamic model was developed to facilitate computer analysis of the circadian-episodic influx of cortisol into plasma from the adrenal gland. The model consists of a catenary system of a biorhythmic control, the adrenal gland, and a body compartment containing circulating cortisol. Computer nonlinear regression analysis was carried out on data consisting of plasma cortisol concentrations measured at 30-min intervals over 1 day in a group of normal children. Circadian rhythmic synthesis of cortisol by the adrenal gland was described by a sinusoidal function which provides the level (284 plus or minus 50 mugg/h/m2) and amplitude (245 plus or minus 50 mug/h/m2) of the synthesis rate and the period (24 hours) and acrophase (8.14 plus or minus 1.95 h) of the cycle. Cosinor analysis of the data confirmed a highly significant circadian rhythm in the daily synthesis rate of cortisol. Episodic secretion, described by an empirical switch function, is assumed to result from accumulation of small amounts of cortisol precursors in the adrenal gland and intermittent stimulation of cortisol release by ACTH. This was found to take place over 46.6 plus or minus 2.4% of a 24-h day. Circulating cortisol is contained in a single body compartment with an apparent volume of distribution (5.3 plus or minus 0.55 liters/m2) from which elimination occurs by first-order metabolic clearance. The biological half-life averaged 0.96 plus or minus 0.18 h. Upon least-square optimization of selected kinetic parameters, the circadian-episodic model increases the accountable variation (r2 x 100) to 89% in comparison with the 35% obtained by use of only a periodic function."} {"id": "PMID:163973", "title": "Ethidium bromide inhibits appearance of closed circular viral DNA and integration of virus-specific DNA in duck cells infected by avian sarcoma virus.", "content": "The DNA of avian sarcoma virus assumes a closed circular configuration before integration into the host cell chromosomal DNA. Ethidium bromide reduces the formation of superhelical viral DNA and concurrently blocks integration of the viral genome. Inhibition of integration of viral DNA results in the inhibition of virus replication.", "contents": "Ethidium bromide inhibits appearance of closed circular viral DNA and integration of virus-specific DNA in duck cells infected by avian sarcoma virus. The DNA of avian sarcoma virus assumes a closed circular configuration before integration into the host cell chromosomal DNA. Ethidium bromide reduces the formation of superhelical viral DNA and concurrently blocks integration of the viral genome. Inhibition of integration of viral DNA results in the inhibition of virus replication."} {"id": "PMID:163980", "title": "Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids.", "content": "Corticosteroids as well as non-steroid anti-inflammatory drugs inhibit the prostaglandin-mediated vasodilatation accompanying lipolysis in subcutaneous fat. Whereas the non-steroids produce their effect by inhibition of prostaglandin synthesis, however, corticosteroids inhibit their release. This mechanism may be the basis of some actions of corticosteroids in inflammation, in the gastric mucosa and in the CNS.", "contents": "Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids. Corticosteroids as well as non-steroid anti-inflammatory drugs inhibit the prostaglandin-mediated vasodilatation accompanying lipolysis in subcutaneous fat. Whereas the non-steroids produce their effect by inhibition of prostaglandin synthesis, however, corticosteroids inhibit their release. This mechanism may be the basis of some actions of corticosteroids in inflammation, in the gastric mucosa and in the CNS."} {"id": "PMID:163989", "title": "Potentation of the cardiac response to aminophylline by oxyfedrine.", "content": "The influence of oxyfedrine on the cardiostimulatory effects of aminophylline was studied in the isolated perfused guinea-pig heart. It was found that oxyfedrine potentiated the stimulatory effects of aminophylline on isometric contraction, dF/dt, coronary flow and heart rate. This potentation was abolished after pretreatment with propranolol. Histamine, though to a lesser extent, also potentiated the effects of aminophylline. When oxyfedrine and histamine were infused simultaneously in the presence of propranolol, the response of the heart to aminophylline was also potentiated; the magnitude of this potentiation was comparable to that obtained with histamine alone, indicating that propranolol abolished only the action of oxyfedrine but not that of histamine. The mechanical effects of aminophylline were accompanied by a slight (15 per cent) but significant inhibition of phosphodiesterase, which was not further augmented by oxyfedrine. The results suggest that the potentiating effects of oxyfedrine or histamine on the cardiostimulatory actions of aminophylline are elicited by their stimulatory actions on adenylate cyclase activity.", "contents": "Potentation of the cardiac response to aminophylline by oxyfedrine. The influence of oxyfedrine on the cardiostimulatory effects of aminophylline was studied in the isolated perfused guinea-pig heart. It was found that oxyfedrine potentiated the stimulatory effects of aminophylline on isometric contraction, dF/dt, coronary flow and heart rate. This potentation was abolished after pretreatment with propranolol. Histamine, though to a lesser extent, also potentiated the effects of aminophylline. When oxyfedrine and histamine were infused simultaneously in the presence of propranolol, the response of the heart to aminophylline was also potentiated; the magnitude of this potentiation was comparable to that obtained with histamine alone, indicating that propranolol abolished only the action of oxyfedrine but not that of histamine. The mechanical effects of aminophylline were accompanied by a slight (15 per cent) but significant inhibition of phosphodiesterase, which was not further augmented by oxyfedrine. The results suggest that the potentiating effects of oxyfedrine or histamine on the cardiostimulatory actions of aminophylline are elicited by their stimulatory actions on adenylate cyclase activity."} {"id": "PMID:163990", "title": "The effect of diuretics on Na+-K+-ATPase and c-AMP levels in toad bladder epithelial cells.", "content": "Na+-K+-ATPase was inhibited by 1 times 10-4M ethacrynic acid and mercuderamide, and by 1 times 10-3M hydrochlorothiazide and furosemide. A modification of Gilman's (1970) protein displacement assay has been used to measure c-AMP levels in toad bladder epithelial cells. Vasopressin (50 mU/ml) caused c-AMP levels to rise from 4.27 to 9.27 pmol/mg protein. Ethacrynic acid had no effect on cellular c-AMP levels after 10 min exposure to the drug, but at 90 min caused a reduction of both basal and vasopressin stimulated levels. Furosemide caused an apparent rise in c-AMP levels, dilution ratio measurements indicated interference by this drug in the assay procedure, mecuderamide also caused substantial interference with the c-AMP assay. Hydrochlorothiazide had no effect on basal or hormone stimulated levels of c-AMP. It was concluded that the inhibition of sodium transport produced by ethacrynic acid in toad bladder is probably due to inhibition of adenylate cyclase, an effect not shared by other dieuretics.", "contents": "The effect of diuretics on Na+-K+-ATPase and c-AMP levels in toad bladder epithelial cells. Na+-K+-ATPase was inhibited by 1 times 10-4M ethacrynic acid and mercuderamide, and by 1 times 10-3M hydrochlorothiazide and furosemide. A modification of Gilman's (1970) protein displacement assay has been used to measure c-AMP levels in toad bladder epithelial cells. Vasopressin (50 mU/ml) caused c-AMP levels to rise from 4.27 to 9.27 pmol/mg protein. Ethacrynic acid had no effect on cellular c-AMP levels after 10 min exposure to the drug, but at 90 min caused a reduction of both basal and vasopressin stimulated levels. Furosemide caused an apparent rise in c-AMP levels, dilution ratio measurements indicated interference by this drug in the assay procedure, mecuderamide also caused substantial interference with the c-AMP assay. Hydrochlorothiazide had no effect on basal or hormone stimulated levels of c-AMP. It was concluded that the inhibition of sodium transport produced by ethacrynic acid in toad bladder is probably due to inhibition of adenylate cyclase, an effect not shared by other dieuretics."} {"id": "PMID:163994", "title": "Management of pregnancy in osteogenesis imperfecta: new perspectives.", "content": "Osteogenesis imperfecta during pregnancy presents increased risk to mother and fetus. In addition to the well-known skeletal changes, other recently recognized metabolic abnormalities also may lead to maternal and fetal problems during labor and delivery. A discussion of risk factors and their managment is presented. The importance of considering the possibility of fetal osteogenesis imperfecta is stressed, and cesarean section is presented as the method of choice for delivery. Important genetic factors including the lack of correlation between the severity of involvement of parent and offspring and the use of pyrophosphate analyses are discussed. An illustrative case is presented.", "contents": "Management of pregnancy in osteogenesis imperfecta: new perspectives. Osteogenesis imperfecta during pregnancy presents increased risk to mother and fetus. In addition to the well-known skeletal changes, other recently recognized metabolic abnormalities also may lead to maternal and fetal problems during labor and delivery. A discussion of risk factors and their managment is presented. The importance of considering the possibility of fetal osteogenesis imperfecta is stressed, and cesarean section is presented as the method of choice for delivery. Important genetic factors including the lack of correlation between the severity of involvement of parent and offspring and the use of pyrophosphate analyses are discussed. An illustrative case is presented."} {"id": "PMID:163995", "title": "Progesterone concentration in placenta, molar tissue, and ovarian theca lutein cyst.", "content": "Progesterone concentrations in 2 full-term normal placentas, molar tissue from 3 cases of hydatidiform mole were measured by competitive protein binding. Sephadex LH-20 column chromatographic separation of extracts from these tissues showed that, in placental and molar tissue, 85 to 95% of the extracts were progesterone and very small amounts of 20 alpha-dihydroprogesterone and 17 alpha-hydroxyprogesterone. The concentration of progesterone in the placenta were 368.8 and 317.2 ng/g tissue, respectively, while in molar tissue the concentration were 2474.5, 1974.6, and 4146.0 ng/g tissue, respectively. Progesterone concentration in ovarian tissue was between 1121;2 and 1440.9 ng/g tissue. It is suggested that the high concentration of progesterone in molar tissue reflects functional capacity of the abnormal trophoblast in progesterone synthesis and accumulation of progesterone due to absence of a fetus. The lower concentration of progesterone in the ovary in molar pregnancy would appear to suggest that the ovary is a secondary source of progesterone in molar pregnancy.", "contents": "Progesterone concentration in placenta, molar tissue, and ovarian theca lutein cyst. Progesterone concentrations in 2 full-term normal placentas, molar tissue from 3 cases of hydatidiform mole were measured by competitive protein binding. Sephadex LH-20 column chromatographic separation of extracts from these tissues showed that, in placental and molar tissue, 85 to 95% of the extracts were progesterone and very small amounts of 20 alpha-dihydroprogesterone and 17 alpha-hydroxyprogesterone. The concentration of progesterone in the placenta were 368.8 and 317.2 ng/g tissue, respectively, while in molar tissue the concentration were 2474.5, 1974.6, and 4146.0 ng/g tissue, respectively. Progesterone concentration in ovarian tissue was between 1121;2 and 1440.9 ng/g tissue. It is suggested that the high concentration of progesterone in molar tissue reflects functional capacity of the abnormal trophoblast in progesterone synthesis and accumulation of progesterone due to absence of a fetus. The lower concentration of progesterone in the ovary in molar pregnancy would appear to suggest that the ovary is a secondary source of progesterone in molar pregnancy."} {"id": "PMID:163996", "title": "Cytomegalovirus endometritis: report of a case associated with spontaneous abortion.", "content": "Maternal cytomegalovirus infection is a relatively common, yet very often silent complication of pregnancy. The association between early gestational wastage and cytomegalovirus endometritis has been documented in recent tissue culture studies without the morphologic demonstration of the virus. This case study presents the clinical and pathologic findings of a young, secundigravida female with cytomegalovirus endometritis and spontaneous abortion. The intranuclear inclusions were restricted to the endometrial glands; Involvement of the endocervix by cytomegalovirus has been the only site in the female reproductive tract, excluding fetal tissues, affected by this virus which has been demonstrated histologically. The data are still incomplete regarding the etiologic role, if any, of cytomegalovirus and the occurrence of spontaneous abortion.", "contents": "Cytomegalovirus endometritis: report of a case associated with spontaneous abortion. Maternal cytomegalovirus infection is a relatively common, yet very often silent complication of pregnancy. The association between early gestational wastage and cytomegalovirus endometritis has been documented in recent tissue culture studies without the morphologic demonstration of the virus. This case study presents the clinical and pathologic findings of a young, secundigravida female with cytomegalovirus endometritis and spontaneous abortion. The intranuclear inclusions were restricted to the endometrial glands; Involvement of the endocervix by cytomegalovirus has been the only site in the female reproductive tract, excluding fetal tissues, affected by this virus which has been demonstrated histologically. The data are still incomplete regarding the etiologic role, if any, of cytomegalovirus and the occurrence of spontaneous abortion."} {"id": "PMID:163998", "title": "Ultrastructural study of focal epithelial hyperplasia.", "content": "Biopsy material from two young Israeli patients with focal epithelial hyperplasia revealed acanthosis, papillomatosis, and the presence of many epithelial cells with a clear cytoplasm in the basale and stratum spinosum. Many of the inclusions seen with the electron microscope had the morphologic appearance of lysosomes, but definite identification must await cytochemical evidence.", "contents": "Ultrastructural study of focal epithelial hyperplasia. Biopsy material from two young Israeli patients with focal epithelial hyperplasia revealed acanthosis, papillomatosis, and the presence of many epithelial cells with a clear cytoplasm in the basale and stratum spinosum. Many of the inclusions seen with the electron microscope had the morphologic appearance of lysosomes, but definite identification must await cytochemical evidence."} {"id": "PMID:163999", "title": "Ultrastructure of an odontogenic myxoma.", "content": "The ultrastructural findings in a case of odontogenic myxoma are described. The main cell type was characterized by several cytoplasmic processes, intracytoplasmic fibrils, numerous glycogen particles, and salient Golgi complexes. A few mitochondria and a scarce endoplasmic reticulum was noted. The matrix consisted of numerous granules with fibrillar projections, collagen bundles, and smaller fibers. The over-all ultrastructural features of this tumor were similar to those described in the human cardiac myxoma and in Wharton's jelly and could be clearly differentiated from the fine structural characteristics of other connective tissue tumors.", "contents": "Ultrastructure of an odontogenic myxoma. The ultrastructural findings in a case of odontogenic myxoma are described. The main cell type was characterized by several cytoplasmic processes, intracytoplasmic fibrils, numerous glycogen particles, and salient Golgi complexes. A few mitochondria and a scarce endoplasmic reticulum was noted. The matrix consisted of numerous granules with fibrillar projections, collagen bundles, and smaller fibers. The over-all ultrastructural features of this tumor were similar to those described in the human cardiac myxoma and in Wharton's jelly and could be clearly differentiated from the fine structural characteristics of other connective tissue tumors."} {"id": "PMID:164001", "title": "Symposium on sensorineural hearing loss in children: early detection and intervention. Impedance measurement.", "content": "Although impedance measurement is a relatively new procedure, at least in this country, it is rapidly being recognized as one of the most significant contributions since the development of the pure tone audiometer. With the basic applications of the procedure it is possible to determine not only the presence but also to a great extent the specific nature of middle ear impairment, even in patients for whom audiometric results are limited and uncertain. Further applications of impedance measurement include the determination of nonorganic hearing loss and site-of-lesion testing to distinguish between cochlear and retrocochlear lesions. Finally it appears that the procedure may even permit the prediction of severity and configuration of sensorineural loss. Although impedance measurement has great value in all patients with hearing disorders, it is particularly appropriate in pediatric evaluation. Its objectivity, its ease of application, and the information that can be obtained with it make impedance measurement a significant and valuable addition to the battery for evaluation of hearing disorders in children.", "contents": "Symposium on sensorineural hearing loss in children: early detection and intervention. Impedance measurement. Although impedance measurement is a relatively new procedure, at least in this country, it is rapidly being recognized as one of the most significant contributions since the development of the pure tone audiometer. With the basic applications of the procedure it is possible to determine not only the presence but also to a great extent the specific nature of middle ear impairment, even in patients for whom audiometric results are limited and uncertain. Further applications of impedance measurement include the determination of nonorganic hearing loss and site-of-lesion testing to distinguish between cochlear and retrocochlear lesions. Finally it appears that the procedure may even permit the prediction of severity and configuration of sensorineural loss. Although impedance measurement has great value in all patients with hearing disorders, it is particularly appropriate in pediatric evaluation. Its objectivity, its ease of application, and the information that can be obtained with it make impedance measurement a significant and valuable addition to the battery for evaluation of hearing disorders in children."} {"id": "PMID:164009", "title": "Bioregulation of lysosomal enzyme secretion from human neutrophils: roles of guanosine 3':5'-monophosphate and calcium in stimulus-secretion coupling.", "content": "The biologic role of calcium and guanosine 3':5'-monophosphate (cyclic GMP) in the immunologic secretion of lysosomal enzymes from human neutrophils was studied. Contact of neutrophils with zymosan-treated serum or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) secretion and a concomitant accumulation of cyclic GMP without any loss of cell viability. Acetylcholine (0.1 muM), in the presence of calcium, enhanced the immunologic stimulation of cyclic GMP accumulation and lysosomal enzyme discharge. A marked and rapid association of 45CaCl2 with neutrophils occurred during cell surface contact with zymosan-treated serum, and this effect on calcium association was enhanced with 0.1 muM acetylcholine. The precise mechanism of the neutrophil-calcium interaction is presently not well understood. However, the finding that 0.5-1.0 muM A-23187 also provoked a rapid association of extracellular calcium with neutrophils suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between cells and calcium. The close temporal relationship between beta-glucuronidase secretion, cyclic GMP accumulation, and calcium mobilization during cell contact with membrane active agents such as immune reactants, acetylcholine, and ionophores suggests that these three cellular events bear a cause and effect relationship. On the basis of our findings to date, we propose that the immunologic secretion of lysosomal contents from human neutrophils is signaled by intracellular cyclic GMP and that extracellular calcium, by gaining access to the intracellular processes responsible for cyclic GMP accumulation, serves as the link to stimulus-secretion coupling.", "contents": "Bioregulation of lysosomal enzyme secretion from human neutrophils: roles of guanosine 3':5'-monophosphate and calcium in stimulus-secretion coupling. The biologic role of calcium and guanosine 3':5'-monophosphate (cyclic GMP) in the immunologic secretion of lysosomal enzymes from human neutrophils was studied. Contact of neutrophils with zymosan-treated serum or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) secretion and a concomitant accumulation of cyclic GMP without any loss of cell viability. Acetylcholine (0.1 muM), in the presence of calcium, enhanced the immunologic stimulation of cyclic GMP accumulation and lysosomal enzyme discharge. A marked and rapid association of 45CaCl2 with neutrophils occurred during cell surface contact with zymosan-treated serum, and this effect on calcium association was enhanced with 0.1 muM acetylcholine. The precise mechanism of the neutrophil-calcium interaction is presently not well understood. However, the finding that 0.5-1.0 muM A-23187 also provoked a rapid association of extracellular calcium with neutrophils suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between cells and calcium. The close temporal relationship between beta-glucuronidase secretion, cyclic GMP accumulation, and calcium mobilization during cell contact with membrane active agents such as immune reactants, acetylcholine, and ionophores suggests that these three cellular events bear a cause and effect relationship. On the basis of our findings to date, we propose that the immunologic secretion of lysosomal contents from human neutrophils is signaled by intracellular cyclic GMP and that extracellular calcium, by gaining access to the intracellular processes responsible for cyclic GMP accumulation, serves as the link to stimulus-secretion coupling."} {"id": "PMID:164010", "title": "Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin.", "content": "Adrenocorticotropic hormone (ACTH) inhibited [3H]thymidine incorporation in normal adrenocortical cells of adult rats in culture, with a concomitant increase in corticosterone production and a characteristic retraction of cells. Both dibutyryl cyclic AMP and an analog of ACTH, which produces virtually no cyclic AMP, inhibited DNA synthesis and stimulated steroid production. ACTH inhibited the proliferation of adrenocortical cells obtained from suckling rats as well as the cells obtained from the capsular tissue of adult rat adrenal glands, whereas insulin caused a stimulation of DNA synthesis. These results suggest that the major role of ACTH is to induce the transformation of the undifferentiated cells of the adrenal gland into functional fasciculata cells and that the proliferation of adrenocortical cells may be under control of factors other than ACTH.", "contents": "Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin. Adrenocorticotropic hormone (ACTH) inhibited [3H]thymidine incorporation in normal adrenocortical cells of adult rats in culture, with a concomitant increase in corticosterone production and a characteristic retraction of cells. Both dibutyryl cyclic AMP and an analog of ACTH, which produces virtually no cyclic AMP, inhibited DNA synthesis and stimulated steroid production. ACTH inhibited the proliferation of adrenocortical cells obtained from suckling rats as well as the cells obtained from the capsular tissue of adult rat adrenal glands, whereas insulin caused a stimulation of DNA synthesis. These results suggest that the major role of ACTH is to induce the transformation of the undifferentiated cells of the adrenal gland into functional fasciculata cells and that the proliferation of adrenocortical cells may be under control of factors other than ACTH."} {"id": "PMID:164011", "title": "An electron microscopic study of virus particles in rhesus monkey placenta.", "content": "Examination of chorionic villi from rhesus monkey placenta revealed the presence of C-type virus particles budding from syncytial trophoblast, pericytes, Hofbauer cells, and mesenchyme. In addition, particles, were found budding from cells of the cytotrophoblastic cell column and decidual basalis. They measured 30 nm in diameter, had a dense central core, surrounded by a narrow, electron-lucent zone, and were enclosed by an outer unit membrane.", "contents": "An electron microscopic study of virus particles in rhesus monkey placenta. Examination of chorionic villi from rhesus monkey placenta revealed the presence of C-type virus particles budding from syncytial trophoblast, pericytes, Hofbauer cells, and mesenchyme. In addition, particles, were found budding from cells of the cytotrophoblastic cell column and decidual basalis. They measured 30 nm in diameter, had a dense central core, surrounded by a narrow, electron-lucent zone, and were enclosed by an outer unit membrane."} {"id": "PMID:164012", "title": "Biosynthesis of polypeptides of cytochrome c oxidase by isolated mitochondria.", "content": "Yeast mitochondria, incubated with radioactive amino acids in a \"protein-synthesizing mixture\" containing an oxidizable substrate and an ATP regenerating system, have been shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to incorporate label into polypeptides equivalent in molecular weight and relative amount ot those made in vivo in the presence of cycloheximide. The ability of these isolated mitochondria to synthesize \"native\" polypeptides was assessed by examining the incorporation of label into subunits of cytochrome c oxidase (EC 1.9.3.1). An analysis of immunoprecipitates formed by incubating cholate extracts of labeled mitochondria with an antiserum against holocytochrome c oxidase revealed that label was incorporated into three polypeptides of sizes equivalent to those of cytochrome c oxidase subunits I, II, and III, shown from earlier studies in vivo to be translated on mitochondrial ribosomes. Further evidence that these polypeptides made in vitro are \"native\" and identical to subunits I, II, and III was provided by the observation that labeled polypeptides equivalent in size to subunits I-III- ARE ALSO IMMUNO-PRECIPITATED BY ANTISERUM AGAINST SUBUNITS V plus VII, an antiserum that can precipitate subunits I, II, and III only when they are complexed to the cytoplasmically synthesized subunits, V and VII, of the enzyme. These results suggest that isolated mitochondria are capable of synthesizing three subunits of cytochrome c oxidase and assembling them into a holoenzyme.", "contents": "Biosynthesis of polypeptides of cytochrome c oxidase by isolated mitochondria. Yeast mitochondria, incubated with radioactive amino acids in a \"protein-synthesizing mixture\" containing an oxidizable substrate and an ATP regenerating system, have been shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to incorporate label into polypeptides equivalent in molecular weight and relative amount ot those made in vivo in the presence of cycloheximide. The ability of these isolated mitochondria to synthesize \"native\" polypeptides was assessed by examining the incorporation of label into subunits of cytochrome c oxidase (EC 1.9.3.1). An analysis of immunoprecipitates formed by incubating cholate extracts of labeled mitochondria with an antiserum against holocytochrome c oxidase revealed that label was incorporated into three polypeptides of sizes equivalent to those of cytochrome c oxidase subunits I, II, and III, shown from earlier studies in vivo to be translated on mitochondrial ribosomes. Further evidence that these polypeptides made in vitro are \"native\" and identical to subunits I, II, and III was provided by the observation that labeled polypeptides equivalent in size to subunits I-III- ARE ALSO IMMUNO-PRECIPITATED BY ANTISERUM AGAINST SUBUNITS V plus VII, an antiserum that can precipitate subunits I, II, and III only when they are complexed to the cytoplasmically synthesized subunits, V and VII, of the enzyme. These results suggest that isolated mitochondria are capable of synthesizing three subunits of cytochrome c oxidase and assembling them into a holoenzyme."} {"id": "PMID:164013", "title": "Cyclic AMP-dependent endogenous phosphorylation of a microtubule-associated protein.", "content": "Microtubules prepared from chick brain homogenates by successive cycles of assembly-disassembly were found to contain two high-molecular-weight proteins, designated microtubule-associated protein1 and microtubule-associated protein2. Microtubule-associated protein2 (apparent molecular weight 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) was the preferred substrate for an endogenous cyclic AMP-dependent protein kinase which appeared to be an integral component of the microtubules. The initial rate of phosphorylation of microtubule-associated protein2 was enhanced 4- to 6-fold by cyclic AMP, with half-maximal stimulation occurring at 2 times 10-7 M cyclic AMP. Under optimal conditions, a total of 1.0 and 1.9 mol of phosphate was incorporated per mole of microtubule-associated protein2, in the absence and presence of cyclic AMP, respectively. Cyclic AMP also stimulated the phosphorylation of tubulin, but the rate of phosphate incorporation per mol of tubulin was only 0.15% that of microtubule-associated protein2. The data raise the possibility that the cyclic AMP-dependent phosphorylation of microtubule-associated protein 2 may play a role in microtubule assembly or function.", "contents": "Cyclic AMP-dependent endogenous phosphorylation of a microtubule-associated protein. Microtubules prepared from chick brain homogenates by successive cycles of assembly-disassembly were found to contain two high-molecular-weight proteins, designated microtubule-associated protein1 and microtubule-associated protein2. Microtubule-associated protein2 (apparent molecular weight 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) was the preferred substrate for an endogenous cyclic AMP-dependent protein kinase which appeared to be an integral component of the microtubules. The initial rate of phosphorylation of microtubule-associated protein2 was enhanced 4- to 6-fold by cyclic AMP, with half-maximal stimulation occurring at 2 times 10-7 M cyclic AMP. Under optimal conditions, a total of 1.0 and 1.9 mol of phosphate was incorporated per mole of microtubule-associated protein2, in the absence and presence of cyclic AMP, respectively. Cyclic AMP also stimulated the phosphorylation of tubulin, but the rate of phosphate incorporation per mol of tubulin was only 0.15% that of microtubule-associated protein2. The data raise the possibility that the cyclic AMP-dependent phosphorylation of microtubule-associated protein 2 may play a role in microtubule assembly or function."} {"id": "PMID:164014", "title": "Interferon action II. Membrane-bound alkaline ribonuclease activity in chick embryo cells manifesting interferon-mediated interference.", "content": "Membrane fractions from chick embryo cells manifesting viral interference mediated by interferon or poly(I)-poly(C) contain high levels of an alkaline ribonuclease. Enhanced RNase activity is not observed when inhibitors of cell protein or RNA synthesis are present during interferon treatment, or when heterologous interferon is used. The RNase associated with comparable membrane fractions from cells treated with mock-interferon is about 1/10 as active, and shows qualitative differences. In principle, divergent views of interferon action may be reconciled to a common mode of action by postulating that viral interference results from a newly induced or activated RNase of cellular origin and proper specificity that acts to reduce the accumulation and functional capacity of newly synthesized viral RNAs, particularly mRNA. Previous data in support of interferon's acting to inhibit virion-derived transcription in vivo are now interpreted as demonstrating enhanced degradation of viral transcripts (mRNA).", "contents": "Interferon action II. Membrane-bound alkaline ribonuclease activity in chick embryo cells manifesting interferon-mediated interference. Membrane fractions from chick embryo cells manifesting viral interference mediated by interferon or poly(I)-poly(C) contain high levels of an alkaline ribonuclease. Enhanced RNase activity is not observed when inhibitors of cell protein or RNA synthesis are present during interferon treatment, or when heterologous interferon is used. The RNase associated with comparable membrane fractions from cells treated with mock-interferon is about 1/10 as active, and shows qualitative differences. In principle, divergent views of interferon action may be reconciled to a common mode of action by postulating that viral interference results from a newly induced or activated RNase of cellular origin and proper specificity that acts to reduce the accumulation and functional capacity of newly synthesized viral RNAs, particularly mRNA. Previous data in support of interferon's acting to inhibit virion-derived transcription in vivo are now interpreted as demonstrating enhanced degradation of viral transcripts (mRNA)."} {"id": "PMID:164015", "title": "Natural occurrence of poly(ADP-ribosyl) histones in rat liver.", "content": "Poly(ADP-ribose) bound to histones has been isolated from rat liver. When [14C]ribose was administered intraperitoneally to rats at a dosage of 300-750 mug (100-250 muCi)/10o g, approximately 1% of the radioactivity was recovered in the acid (5% CLCCCOOH)-INSOLUBLE MATERIAL OF THE LIVER NUCLEI 2 HR AFTER INJECTION. Of the acid-insoluble radioactivity, 4.5-9% was extractable with 0.25 N HCL. Carboxymethyl-cellulose column chromatography of the HCl-extracted material revealed that the radioactivity cochromatographed with histone subfractions f1 and, to a lesser extent, f2 and f3. Part of the protein-bound radioactivity was rendered acid-soluble by treatment with either snake venom phosphodiesterase or neutral NH2OH. From the enzyme digest, 5'-AMP and psiADP-ribose [2'-(5\"-phosphoribosyl)-5'-AMP] were recovered, while the NH2OH treatment yielded ADP-ribose monomer and, presumably, oligomer. These observations indicate that ADP-ribose is attached to histones in vivo and is present both as a monomer and a polymer.", "contents": "Natural occurrence of poly(ADP-ribosyl) histones in rat liver. Poly(ADP-ribose) bound to histones has been isolated from rat liver. When [14C]ribose was administered intraperitoneally to rats at a dosage of 300-750 mug (100-250 muCi)/10o g, approximately 1% of the radioactivity was recovered in the acid (5% CLCCCOOH)-INSOLUBLE MATERIAL OF THE LIVER NUCLEI 2 HR AFTER INJECTION. Of the acid-insoluble radioactivity, 4.5-9% was extractable with 0.25 N HCL. Carboxymethyl-cellulose column chromatography of the HCl-extracted material revealed that the radioactivity cochromatographed with histone subfractions f1 and, to a lesser extent, f2 and f3. Part of the protein-bound radioactivity was rendered acid-soluble by treatment with either snake venom phosphodiesterase or neutral NH2OH. From the enzyme digest, 5'-AMP and psiADP-ribose [2'-(5\"-phosphoribosyl)-5'-AMP] were recovered, while the NH2OH treatment yielded ADP-ribose monomer and, presumably, oligomer. These observations indicate that ADP-ribose is attached to histones in vivo and is present both as a monomer and a polymer."} {"id": "PMID:164016", "title": "The antagonistic effect of an inhalation anesthetic and high pressure on the phase diagram of mixed dipalmitoyl-dimyristoylphosphatidylcholine bilayers.", "content": "Several workers have shown that phase transition-related changes in membrane lipids have a profound effect on membrane-solvated protein function. This phase transition temperature dependence has been explained as resulting from the formation of lateral phase separations within the membrane bilayer. The present study demonstrates that a clinical concentration of an inhalation anesthetic produces changes in both the phase transition temperature of pure lipid bilayers and the lateral phase separation temperature of mixed dipalmitoyl- and dimyristoylphosphatidylcholine bilayers of a magnitude sufficient to influence protein function. It is further shown that pressure is able to antagonize the effect of the anesthetic on these transition temperatures. It is proposed that anesthetic action within nerve membranes may be the result of changes in the lateral phase separation-controlled environment of the membrane-solvated proteins essential to nerve function.", "contents": "The antagonistic effect of an inhalation anesthetic and high pressure on the phase diagram of mixed dipalmitoyl-dimyristoylphosphatidylcholine bilayers. Several workers have shown that phase transition-related changes in membrane lipids have a profound effect on membrane-solvated protein function. This phase transition temperature dependence has been explained as resulting from the formation of lateral phase separations within the membrane bilayer. The present study demonstrates that a clinical concentration of an inhalation anesthetic produces changes in both the phase transition temperature of pure lipid bilayers and the lateral phase separation temperature of mixed dipalmitoyl- and dimyristoylphosphatidylcholine bilayers of a magnitude sufficient to influence protein function. It is further shown that pressure is able to antagonize the effect of the anesthetic on these transition temperatures. It is proposed that anesthetic action within nerve membranes may be the result of changes in the lateral phase separation-controlled environment of the membrane-solvated proteins essential to nerve function."} {"id": "PMID:164017", "title": "Translation and identification of the mRNA species synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus.", "content": "Vesicular stomatitis virus messenger RNA has been transcribed in vitro from the viral genome by the virion-associated RNA polymerase in quantities suitable for translation. Wheat germ cell-free extracts programmed with the isolated in vitro 12-18S RNA fraction synthesize polypeptides similar to the viral N, NS, and M proteins, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping of the in vitro products and the viral marker polypeptides. In addition, the RNA synthesized in vitro also codes for a protein of molecular weight 63,000 which may be a nonglycosylated form of the viral glycoprotein G. The 12-18S RNA has been partially separated into individual messenger species and these have been identified by the proteins for which they code. There are four monocistronic messenger species in the in vitro 12-18S RNA and the coding capacity of three of these molecules agrees with the estimated molecular weight of the polypeptide assigned to it.", "contents": "Translation and identification of the mRNA species synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus. Vesicular stomatitis virus messenger RNA has been transcribed in vitro from the viral genome by the virion-associated RNA polymerase in quantities suitable for translation. Wheat germ cell-free extracts programmed with the isolated in vitro 12-18S RNA fraction synthesize polypeptides similar to the viral N, NS, and M proteins, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping of the in vitro products and the viral marker polypeptides. In addition, the RNA synthesized in vitro also codes for a protein of molecular weight 63,000 which may be a nonglycosylated form of the viral glycoprotein G. The 12-18S RNA has been partially separated into individual messenger species and these have been identified by the proteins for which they code. There are four monocistronic messenger species in the in vitro 12-18S RNA and the coding capacity of three of these molecules agrees with the estimated molecular weight of the polypeptide assigned to it."} {"id": "PMID:164018", "title": "Methylated nucleotides block 5'-terminus of vaccinia virus messenger RNA.", "content": "Studies on the nature and location of the methylated nucleotides in mRNA synthesized in vitro by vaccinia virus particles revealed an unusual 5'-terminal structure. Evidence that the pyrophosphate group is blocked by 7-methylguanosine and that both 2'-O-methyl-adenosine and 2'-O-methylguanosine occupy penultimate positions was presented. According to this model, the 5'-termini of vaccinia virus mRNAs are: 7MeG-5'ppp-5'GMepNp and 7MeG-5'AMepNp.", "contents": "Methylated nucleotides block 5'-terminus of vaccinia virus messenger RNA. Studies on the nature and location of the methylated nucleotides in mRNA synthesized in vitro by vaccinia virus particles revealed an unusual 5'-terminal structure. Evidence that the pyrophosphate group is blocked by 7-methylguanosine and that both 2'-O-methyl-adenosine and 2'-O-methylguanosine occupy penultimate positions was presented. According to this model, the 5'-termini of vaccinia virus mRNAs are: 7MeG-5'ppp-5'GMepNp and 7MeG-5'AMepNp."} {"id": "PMID:164019", "title": "Competent Bacillus subtilis cultures synthesize a denatured DNA binding activity.", "content": "A protein activity has been detected in soluble extracts of competent cultures of bacillus subtilis which protects denatured DNA from nuclease solubilization. Both binding activity and competence development occur simultaneously but not coordinately, since the peak of binding activity appears 3 hr after the peak of competence. The binding activivity is not detected in physiologically noncompetent cultures, in an isogenic noncompetent cultures, in an isogenic noncompetent mutant grown through the competence regimen, or in early sporulating cells. The activity is included on Sephadex G-100 gel filtration columns but elutes in a broad nonhomogeneous peak. This binding activity may play a role in uptake of DNA and/or integration of exogenous DNA into the genome of competent B. subtilis cells.", "contents": "Competent Bacillus subtilis cultures synthesize a denatured DNA binding activity. A protein activity has been detected in soluble extracts of competent cultures of bacillus subtilis which protects denatured DNA from nuclease solubilization. Both binding activity and competence development occur simultaneously but not coordinately, since the peak of binding activity appears 3 hr after the peak of competence. The binding activivity is not detected in physiologically noncompetent cultures, in an isogenic noncompetent cultures, in an isogenic noncompetent mutant grown through the competence regimen, or in early sporulating cells. The activity is included on Sephadex G-100 gel filtration columns but elutes in a broad nonhomogeneous peak. This binding activity may play a role in uptake of DNA and/or integration of exogenous DNA into the genome of competent B. subtilis cells."} {"id": "PMID:164020", "title": "Mechanism of action of cholera toxin and the mobile receptor theory of hormone receptor-adenylate cyclase interactions.", "content": "Rat liver membrane adenylate cyclase (EC 4.6.1.1) that has been stimulated more than 10-fold by cholera toxin (choleragen) has a 3-fold greater sensitivity to stimulation by glucagon. Choleragen similarly increases the sensitivity of cyclase to other peptide (ACTH, vasoactive intestinal polypeptide) and nonpeptide (catecholamines) hormones in this and other tissues. The rate of 125I-labeled glucagon-membrane dissociation is decreased about 2-fold in toxin-treated liver membranes. Toxin-activated cyclase activity of fat cell membranes is retained upon solubilization with Lubrol PX. Provided 125I-labeled choleragen is first incubated with cells under conditions resulting in enzyme activation, the solubilized cyclase activity migrates with a component of 125I-labeled choleragen on gel filtration chromatography. Agarose derivatives containing the \"active\" subunit (molecular weight 36,000) of the toxin can specifically adsorb solubilized adenylate cyclase. Toxin-stimulated cyclase can be immunoprecipitated with antitoxin or anti-\"active\" subunit antibodies. There is a large excess of membrane receptors (ganglioside GM1) which, with the use of choleragenoid, can be shown to be functionally equivalent with respect to cyclase activation. Choleragenoid, an inactive competitive antagonist of toxin binding, can occupy and block a large proportion of toxin receptors without affecting toxin activity. A scheme of toxin action is proposed that involves lateral membrane diffusion of the initially inactive toxin-receptor complex with subsequent direct interaction with and modulation of adenylate cyclase. The basic features of this scheme may be pertinent to the mechanisms by which hormone receptors normally modulate adenylate cyclase.", "contents": "Mechanism of action of cholera toxin and the mobile receptor theory of hormone receptor-adenylate cyclase interactions. Rat liver membrane adenylate cyclase (EC 4.6.1.1) that has been stimulated more than 10-fold by cholera toxin (choleragen) has a 3-fold greater sensitivity to stimulation by glucagon. Choleragen similarly increases the sensitivity of cyclase to other peptide (ACTH, vasoactive intestinal polypeptide) and nonpeptide (catecholamines) hormones in this and other tissues. The rate of 125I-labeled glucagon-membrane dissociation is decreased about 2-fold in toxin-treated liver membranes. Toxin-activated cyclase activity of fat cell membranes is retained upon solubilization with Lubrol PX. Provided 125I-labeled choleragen is first incubated with cells under conditions resulting in enzyme activation, the solubilized cyclase activity migrates with a component of 125I-labeled choleragen on gel filtration chromatography. Agarose derivatives containing the \"active\" subunit (molecular weight 36,000) of the toxin can specifically adsorb solubilized adenylate cyclase. Toxin-stimulated cyclase can be immunoprecipitated with antitoxin or anti-\"active\" subunit antibodies. There is a large excess of membrane receptors (ganglioside GM1) which, with the use of choleragenoid, can be shown to be functionally equivalent with respect to cyclase activation. Choleragenoid, an inactive competitive antagonist of toxin binding, can occupy and block a large proportion of toxin receptors without affecting toxin activity. A scheme of toxin action is proposed that involves lateral membrane diffusion of the initially inactive toxin-receptor complex with subsequent direct interaction with and modulation of adenylate cyclase. The basic features of this scheme may be pertinent to the mechanisms by which hormone receptors normally modulate adenylate cyclase."} {"id": "PMID:164021", "title": "Effect of a low-molecular-weight DNA binding protein, H1 factor, on the in vitro transcription of the lactose operon in Escherichia coli.", "content": "H1 protein, a heat-stable low-molecular-weight DNA-binding factor previously described by Cukier-Kahn et al. [Proc. Nat. Acad. Sci USA (1972) 69, 3643-3647] markedly stimulates in vitro synthesis of lac-specific RNA directed by bacteriophage lambdah80 dlac or phi80 dlac DNA templates in the presence of purified E. coli RNA polymerase holoenzyme. The extent of stimulation obtained by addition of H1 alone is usually greater than that observed with the cAMP receptor protein-cAMP combination. H1 effect varies quite appreciably (from 4- to 16-fold) with the functional state of the promoter, being much larger with lambdah80 dlac p-s, a transducing DNA carrying a superpromoter mutation, than with lambdah80 dlac p+. H1 and cAMP receptor protein effects are nearly additive, although interpretation of the data obtained at high H1 concentration is complicated by the appearance of some inhibitory property. While the cAMP-receptor-protein-mediated synthesis is asymmetrical (\"I\" strand almost exclusively copied), the degree of asymmetry observed with H1 is less pronounced, suggesting asymmetrical copying from the lac promoter and symmetric transcription from other regions of the DNA. Synthesis of lac-specific RNA from lambdah80 dtrp/lac or phi80 dlac p-r uv5 templates, in which lac promoters are insensitive to cAMP receptor protein, either as a result of lac fusion to the trp operon or mutation in the lac promoter, is totally H1-insensitive. Glycerol (10-15% w/w) can fully substitute for H1 in stimulating lac RNA synthesis in a fashion analogous to that reported for the cAMP receptor protein-cAMP system. The possibility that H1 acts by causing conformational modifications at the promoter level in a way that increases its functional state, and that this effect is more pronounced with operons sensitive to cAMP receptor protein, is discussed.", "contents": "Effect of a low-molecular-weight DNA binding protein, H1 factor, on the in vitro transcription of the lactose operon in Escherichia coli. H1 protein, a heat-stable low-molecular-weight DNA-binding factor previously described by Cukier-Kahn et al. [Proc. Nat. Acad. Sci USA (1972) 69, 3643-3647] markedly stimulates in vitro synthesis of lac-specific RNA directed by bacteriophage lambdah80 dlac or phi80 dlac DNA templates in the presence of purified E. coli RNA polymerase holoenzyme. The extent of stimulation obtained by addition of H1 alone is usually greater than that observed with the cAMP receptor protein-cAMP combination. H1 effect varies quite appreciably (from 4- to 16-fold) with the functional state of the promoter, being much larger with lambdah80 dlac p-s, a transducing DNA carrying a superpromoter mutation, than with lambdah80 dlac p+. H1 and cAMP receptor protein effects are nearly additive, although interpretation of the data obtained at high H1 concentration is complicated by the appearance of some inhibitory property. While the cAMP-receptor-protein-mediated synthesis is asymmetrical (\"I\" strand almost exclusively copied), the degree of asymmetry observed with H1 is less pronounced, suggesting asymmetrical copying from the lac promoter and symmetric transcription from other regions of the DNA. Synthesis of lac-specific RNA from lambdah80 dtrp/lac or phi80 dlac p-r uv5 templates, in which lac promoters are insensitive to cAMP receptor protein, either as a result of lac fusion to the trp operon or mutation in the lac promoter, is totally H1-insensitive. Glycerol (10-15% w/w) can fully substitute for H1 in stimulating lac RNA synthesis in a fashion analogous to that reported for the cAMP receptor protein-cAMP system. The possibility that H1 acts by causing conformational modifications at the promoter level in a way that increases its functional state, and that this effect is more pronounced with operons sensitive to cAMP receptor protein, is discussed."} {"id": "PMID:164022", "title": "Fate of viral RNA of murine leukemia virus after infection.", "content": "[3H]Uridine-labeled Rauscher leukemia virus was used to infect mouse embryo fibroblasts. After the infected cells were separated into nuclear and cytoplasmic fractions nucleic acid was extracted by sodium dodecyl sulfate-phenol-chloroform treatment and analyzed by Cs2SO4 and sucrose density gradient centrifugation. Between 45 and 70 min after infection a transient and synchronized shift of the acid-insoluble radioactive peak toward the RNA-DNA hybrid region occurred in both the nuclear and cytoplasmic fractions. The density of the cytoplasmic hybrid shifted to 1.56 g/ml (RNA equals about 50%), while the sedimentation rate decreased from 36 S to 14 S; however, the density of the nuclear hybrid shifted to 1.58-1.48 g/ml (RNA equals 57-17%, respectively), while its sedimentation rate remained about 65 S. The hybrids in both the nuclear and the cytoplasmic fractions still showed hybrid density after heat denaturation. The processes of the early stages of RNA tumor virus infection are discussed with regard to the functions of viral RNA-dependent DNA polymerase (reverse transcriptase) and a possible integration of viral genetic information into the host chromosome.", "contents": "Fate of viral RNA of murine leukemia virus after infection. [3H]Uridine-labeled Rauscher leukemia virus was used to infect mouse embryo fibroblasts. After the infected cells were separated into nuclear and cytoplasmic fractions nucleic acid was extracted by sodium dodecyl sulfate-phenol-chloroform treatment and analyzed by Cs2SO4 and sucrose density gradient centrifugation. Between 45 and 70 min after infection a transient and synchronized shift of the acid-insoluble radioactive peak toward the RNA-DNA hybrid region occurred in both the nuclear and cytoplasmic fractions. The density of the cytoplasmic hybrid shifted to 1.56 g/ml (RNA equals about 50%), while the sedimentation rate decreased from 36 S to 14 S; however, the density of the nuclear hybrid shifted to 1.58-1.48 g/ml (RNA equals 57-17%, respectively), while its sedimentation rate remained about 65 S. The hybrids in both the nuclear and the cytoplasmic fractions still showed hybrid density after heat denaturation. The processes of the early stages of RNA tumor virus infection are discussed with regard to the functions of viral RNA-dependent DNA polymerase (reverse transcriptase) and a possible integration of viral genetic information into the host chromosome."} {"id": "PMID:164023", "title": "The structure of a yeast hexokinase monomer and its complexes with substrates at 2.7-A resolution.", "content": "From a 2.7-A resolution electron density map we have built a model of the polypeptide backbone of a monomer of yeast hexokinase B (EC 2.7.1.1). This map was obtained from a third crystal form of hexokinase, called BIII, which exhibits space group P212121 and which contains only one monomer per asymmetric unit. The 51,000 molecular weight monomer has an elongated shape (80 A by 55 A by 50 A) and is divided into two lobes by a deep central cleft. The polypeptide chain is folded into three structural domains, one of which is predominantly alpha-helical and two of which each contain a beta-pleated sheet flanked by alpha-helices. Both glucose and AMP bind to these crystals and produce significant alterations in the protein structure. Glucose binds in the deep cleft, as was observed previously in the BII crystal of the dimeric enzyme. AMP, however, binds to a site that is different from the major intersubunit ATP binding site observed in the crystalline dimer. The AMP is found near one of the beta-pleated sheets. From our current interpretation of this electron density map we conclude that neither of the two nucleotide binding regions has the same structure as has been observed for the nucleotide binding regions of the dehydrogenases, adenylate kinase, and phosphoglycerate kinase, although some similarities exist.", "contents": "The structure of a yeast hexokinase monomer and its complexes with substrates at 2.7-A resolution. From a 2.7-A resolution electron density map we have built a model of the polypeptide backbone of a monomer of yeast hexokinase B (EC 2.7.1.1). This map was obtained from a third crystal form of hexokinase, called BIII, which exhibits space group P212121 and which contains only one monomer per asymmetric unit. The 51,000 molecular weight monomer has an elongated shape (80 A by 55 A by 50 A) and is divided into two lobes by a deep central cleft. The polypeptide chain is folded into three structural domains, one of which is predominantly alpha-helical and two of which each contain a beta-pleated sheet flanked by alpha-helices. Both glucose and AMP bind to these crystals and produce significant alterations in the protein structure. Glucose binds in the deep cleft, as was observed previously in the BII crystal of the dimeric enzyme. AMP, however, binds to a site that is different from the major intersubunit ATP binding site observed in the crystalline dimer. The AMP is found near one of the beta-pleated sheets. From our current interpretation of this electron density map we conclude that neither of the two nucleotide binding regions has the same structure as has been observed for the nucleotide binding regions of the dehydrogenases, adenylate kinase, and phosphoglycerate kinase, although some similarities exist."} {"id": "PMID:164025", "title": "Spontaneous and induced mutagenesis in Western Equine encephalomyelitis virus in chick embryo cells with different repair activity.", "content": "Evidence was obtained indicating differences in the survival rate of Western equine encephalomyelitis virus after exposure to ultraviolet radiation and methyl methanesulfonate in commercial and leukosisfree chick embryo cells that differed in repair activity. The levels of spontaneous mutagenesis (on the basis of the yield of small palque variants of the encephalomyelitis virus) did not essentially change when the virus was passage in leukosis-free chick embryo cells, whereas an increase in the number of small palque variants was observed in the cells of commercial chick embryos. A 10-fold increase in the number of induced virus variants was observed in commercial chick embryo cells in experiments with methyl methanesulfonate as compared with the contorl, whereas the induction of virus variants was not noted in leukosis-free cells.", "contents": "Spontaneous and induced mutagenesis in Western Equine encephalomyelitis virus in chick embryo cells with different repair activity. Evidence was obtained indicating differences in the survival rate of Western equine encephalomyelitis virus after exposure to ultraviolet radiation and methyl methanesulfonate in commercial and leukosisfree chick embryo cells that differed in repair activity. The levels of spontaneous mutagenesis (on the basis of the yield of small palque variants of the encephalomyelitis virus) did not essentially change when the virus was passage in leukosis-free chick embryo cells, whereas an increase in the number of small palque variants was observed in the cells of commercial chick embryos. A 10-fold increase in the number of induced virus variants was observed in commercial chick embryo cells in experiments with methyl methanesulfonate as compared with the contorl, whereas the induction of virus variants was not noted in leukosis-free cells."} {"id": "PMID:164024", "title": "Light-stimulated phosphorylation of rhodopsin in the retina: the presence of a protein kinase that is specific for photobleached rhodopsin.", "content": "A protein kinase has been extracted from bovine rod outer segments by a mild procedure. The enzyme acts specifically on photobleached, not unbleached, rhodopsin and will not catalyze the phosphorylation of histones, phosvitin, or casein. We propose the name \"opsin kinase\" for the enzyme, which is not affected by cyclic nucleotides but which is inhibited by theophylline. Preparations of purified rod outer segments, however, appear to contain only low concentration of opsin phosphatase activity.", "contents": "Light-stimulated phosphorylation of rhodopsin in the retina: the presence of a protein kinase that is specific for photobleached rhodopsin. A protein kinase has been extracted from bovine rod outer segments by a mild procedure. The enzyme acts specifically on photobleached, not unbleached, rhodopsin and will not catalyze the phosphorylation of histones, phosvitin, or casein. We propose the name \"opsin kinase\" for the enzyme, which is not affected by cyclic nucleotides but which is inhibited by theophylline. Preparations of purified rod outer segments, however, appear to contain only low concentration of opsin phosphatase activity."} {"id": "PMID:164026", "title": "Cobalt(III), a probe of metal binding sites of Escherichia coli alkaline phosphatase.", "content": "To facilitate the study of individual metal binding sites of polymeric metalloproteins, conversion of exchange-labile Co(II) in E. coli alkaline phosphatase (EC 3.1.3.1) to exchange-inert Co(III) was examined. Oxidation of Co(II) alkaline phosphatase with hydrogen peroxide results in a single absorption maximum at 530 nm and loss both of the characteristic electron paramagnetic signal and of enzymatic activity. Zinc neither reactivates this enzyme nor displaces the oxidized cobalt atoms. Metal and amino-acid analyses demonstrate that oxidation alters neither cobalt binding nor amino-acid composition of the enzyme. Al data are consistent with the conclusion that hydrogen peroxide oxidizes Co(II) in alkaline phosphatase to Co(III). Polymeric metalloenzymes can contain different categories of metal atoms serving in catalysis, structure stabilization, and/or control and exerting their effects independently or interdependently. The in situ conversion of exchange-labile Co(II) to exchange-stable (Co(III) offers a method to selectively and differentially \"freeze\" cobalt atoms at their respective binding sites. The accompanying spectral changes and concomitant retardation in ligand exchange reactions may be used to differentiate between specific metal binding sites that serve different roles in polymeric metalloenzymes.", "contents": "Cobalt(III), a probe of metal binding sites of Escherichia coli alkaline phosphatase. To facilitate the study of individual metal binding sites of polymeric metalloproteins, conversion of exchange-labile Co(II) in E. coli alkaline phosphatase (EC 3.1.3.1) to exchange-inert Co(III) was examined. Oxidation of Co(II) alkaline phosphatase with hydrogen peroxide results in a single absorption maximum at 530 nm and loss both of the characteristic electron paramagnetic signal and of enzymatic activity. Zinc neither reactivates this enzyme nor displaces the oxidized cobalt atoms. Metal and amino-acid analyses demonstrate that oxidation alters neither cobalt binding nor amino-acid composition of the enzyme. Al data are consistent with the conclusion that hydrogen peroxide oxidizes Co(II) in alkaline phosphatase to Co(III). Polymeric metalloenzymes can contain different categories of metal atoms serving in catalysis, structure stabilization, and/or control and exerting their effects independently or interdependently. The in situ conversion of exchange-labile Co(II) to exchange-stable (Co(III) offers a method to selectively and differentially \"freeze\" cobalt atoms at their respective binding sites. The accompanying spectral changes and concomitant retardation in ligand exchange reactions may be used to differentiate between specific metal binding sites that serve different roles in polymeric metalloenzymes."} {"id": "PMID:164027", "title": "Changes of tissue water proton relaxation rates during early phases of chemical carcinogenesis.", "content": "Water proton spin lattice relaxation rate (T1) was determined on tissues of rats experiencing early phases of chemical carcinogenesis. Rats were fed a fast acting carcinogen, 3'-methyldimethylaminoazobenzene, and a slower acting carcinogen, 2-acetylaminofluorene, for up to 4 weeks. T1 of blood serum and liver tissue was significantly higher than those of controls after 4 weeks of 3'-methyldimethylaminoazobenzene feeding. This was not the case for 2-acetylaminofluorene. The blood serum T1 increase reflected the onset of liver nodulation (assumed to be preneoplastic). Liver T1 values increased as the degree of nodulation increased. Blood serum T1 correlated inversely with protein content and directly with water content. Liver T1 values correlated with water content, but this was not true for spleen T1 values. Spleen T1 values were significantly lower than controls at the earliest sampling date for each carcinogen: one week for 3'-methyldimethylaminoazobenzene and 4 weeks for 2-acetylaminofluorene. The spleen T1 decrease paralleled an increase of iron detectable by electron spin resonance in this tissue. Spleen T1 decreases are probably not unique to chemical carcinogenesis.", "contents": "Changes of tissue water proton relaxation rates during early phases of chemical carcinogenesis. Water proton spin lattice relaxation rate (T1) was determined on tissues of rats experiencing early phases of chemical carcinogenesis. Rats were fed a fast acting carcinogen, 3'-methyldimethylaminoazobenzene, and a slower acting carcinogen, 2-acetylaminofluorene, for up to 4 weeks. T1 of blood serum and liver tissue was significantly higher than those of controls after 4 weeks of 3'-methyldimethylaminoazobenzene feeding. This was not the case for 2-acetylaminofluorene. The blood serum T1 increase reflected the onset of liver nodulation (assumed to be preneoplastic). Liver T1 values increased as the degree of nodulation increased. Blood serum T1 correlated inversely with protein content and directly with water content. Liver T1 values correlated with water content, but this was not true for spleen T1 values. Spleen T1 values were significantly lower than controls at the earliest sampling date for each carcinogen: one week for 3'-methyldimethylaminoazobenzene and 4 weeks for 2-acetylaminofluorene. The spleen T1 decrease paralleled an increase of iron detectable by electron spin resonance in this tissue. Spleen T1 decreases are probably not unique to chemical carcinogenesis."} {"id": "PMID:164028", "title": "Genetic heterogeneity in xeroderma pigmentosum: complementation groups and their relationship to DNA repair rates.", "content": "Fibroblast strains from 12 patients with xeroderma pigmentosum had lower than normal rates of DNA repair, as determined by autoradiographic studies of ultraviolet-induced unscheduled nuclear DNA synthesis. The nuclei in binuclear cells, obtained by fusing fibroblasts from certain pairs of these strains, had a greater rate of DNA repair than the nuclei of either strain's unfused mononuclear cells. These results indicate that complementary corrections of the strains' repair defects had occurred in the fused cells. Four complementation groups were found, indicating that at least four mutations caused decreased DNA repair among these 12 strains. The unfused mononuclear cells of each group had a characteristic rate of repair that differed from the rates of the other groups.", "contents": "Genetic heterogeneity in xeroderma pigmentosum: complementation groups and their relationship to DNA repair rates. Fibroblast strains from 12 patients with xeroderma pigmentosum had lower than normal rates of DNA repair, as determined by autoradiographic studies of ultraviolet-induced unscheduled nuclear DNA synthesis. The nuclei in binuclear cells, obtained by fusing fibroblasts from certain pairs of these strains, had a greater rate of DNA repair than the nuclei of either strain's unfused mononuclear cells. These results indicate that complementary corrections of the strains' repair defects had occurred in the fused cells. Four complementation groups were found, indicating that at least four mutations caused decreased DNA repair among these 12 strains. The unfused mononuclear cells of each group had a characteristic rate of repair that differed from the rates of the other groups."} {"id": "PMID:164029", "title": "Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase.", "content": "An activating factor of adenylate cyclase (EC 4.6.1.1) HAS BEEN OBTAINED FROM DETERGENT-DISPERSED PREPARATIONS OF PORCINE CEREBRAL CORTEX BY COLUMN CHROMATOGRAPHY ON ECTEOLA-cellulose. The factor was identified by acrylamide gel electrophoresis and by enzyme activation studies as the Ca2+-binding protein that regulates the activity of a brain cyclic nucleotide phosphodiesterase. This Ca2+-binding protein confers a Ca2+-dependent activation upon the adenylate cyclase, which is reversed by the subsequent addition of egta in excess of the free Ca2+. It is proposed that this Ca2+-dependent regulator controls enzymatic activities responsible for the synthesis of adenosine 3':5'-monophosphate and for the hydrolysis of guanosine 3':5'-monophosphate.", "contents": "Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase. An activating factor of adenylate cyclase (EC 4.6.1.1) HAS BEEN OBTAINED FROM DETERGENT-DISPERSED PREPARATIONS OF PORCINE CEREBRAL CORTEX BY COLUMN CHROMATOGRAPHY ON ECTEOLA-cellulose. The factor was identified by acrylamide gel electrophoresis and by enzyme activation studies as the Ca2+-binding protein that regulates the activity of a brain cyclic nucleotide phosphodiesterase. This Ca2+-binding protein confers a Ca2+-dependent activation upon the adenylate cyclase, which is reversed by the subsequent addition of egta in excess of the free Ca2+. It is proposed that this Ca2+-dependent regulator controls enzymatic activities responsible for the synthesis of adenosine 3':5'-monophosphate and for the hydrolysis of guanosine 3':5'-monophosphate."} {"id": "PMID:164030", "title": "A routine method for protein-free spreading of double- and single-stranded nucleic acid molecules.", "content": "A protein-free nucleic acid preparation method for electron microscopy is described. The basic procedure is very similar to the classical protein monolayer spreading techniques. The carrier protein (usually cytochrome c) is replaced by benzyldimethylalkylammonium chloride. Both the hypophase method and the microdiffusion or droplet method can be applied with this compound. Unlike cytochrome c, benzyldimethylalkylammonium chloride does not lead to any apparent thickening of the nucleic acid strands. Partially denatured DNA spread with this reagent shows a loosened structure with a foamy appearance in the regions previously considered to be \"unmelted,\" which open up locally into melted loops of different size. Specifically bound proteins, such as RNA polymerase on bacteriophage T7 DNA, can be detected unambiguously.", "contents": "A routine method for protein-free spreading of double- and single-stranded nucleic acid molecules. A protein-free nucleic acid preparation method for electron microscopy is described. The basic procedure is very similar to the classical protein monolayer spreading techniques. The carrier protein (usually cytochrome c) is replaced by benzyldimethylalkylammonium chloride. Both the hypophase method and the microdiffusion or droplet method can be applied with this compound. Unlike cytochrome c, benzyldimethylalkylammonium chloride does not lead to any apparent thickening of the nucleic acid strands. Partially denatured DNA spread with this reagent shows a loosened structure with a foamy appearance in the regions previously considered to be \"unmelted,\" which open up locally into melted loops of different size. Specifically bound proteins, such as RNA polymerase on bacteriophage T7 DNA, can be detected unambiguously."} {"id": "PMID:164031", "title": "Differentiation in erythroleukemic cells and their somatic hybrids.", "content": "Clones of erythroleukemic cells differ in the extent to which they (1) undergo differentiation spontaneously and (2) can be induced to differentiate in the presence of dimethylsulfoxide. Here we demonstrate that relative differences in globin gene expression within and between clones largely reflect differences in the proportion of cells participating in differentiation rather than uniform differences in the extent to which all cells in these clones undergo differentiation. We call this phenotype of a clone its characteristic probability of differentiation, a property that reflects the likelihood that a cell of this clone will undergo erythrodifferentiation under given conditions. We have examined somatic hybrid cells formed between similar erythroleukemic lines, between phenotypically different erythroleukemic lines, between phenotypically different erythroleukemic lines, and between erythroleukemic cells and mouse fibroblasts. Results of these experiments demonstrate that the spontaneous and induced probabilities of differentiation may be altered in an uncoupled fashion, suggesting that each is determined at different steps leading to a common pathway of globin gene expression.", "contents": "Differentiation in erythroleukemic cells and their somatic hybrids. Clones of erythroleukemic cells differ in the extent to which they (1) undergo differentiation spontaneously and (2) can be induced to differentiate in the presence of dimethylsulfoxide. Here we demonstrate that relative differences in globin gene expression within and between clones largely reflect differences in the proportion of cells participating in differentiation rather than uniform differences in the extent to which all cells in these clones undergo differentiation. We call this phenotype of a clone its characteristic probability of differentiation, a property that reflects the likelihood that a cell of this clone will undergo erythrodifferentiation under given conditions. We have examined somatic hybrid cells formed between similar erythroleukemic lines, between phenotypically different erythroleukemic lines, between phenotypically different erythroleukemic lines, and between erythroleukemic cells and mouse fibroblasts. Results of these experiments demonstrate that the spontaneous and induced probabilities of differentiation may be altered in an uncoupled fashion, suggesting that each is determined at different steps leading to a common pathway of globin gene expression."} {"id": "PMID:164039", "title": "Neuroradiology of the sphenoidal region.", "content": "The neuroradiological techniques employed in diagnosing a series of 54 lesions involving the superior orbital fissure and cavernous sinus (sphenoidal region) were reviewed in order to compare the value of sphenoidal tomography, pneumoencephalography, cerebral arteriography and sphenoidal venography. The patients included in the series exhibited clinical syndromes of sphenoidal region cranial nerve deficits. Confirmation of the sphenoidal region disorder was obtained in all cases. Of the four procedures, sphenoidal venography and basal tomography yielded the highest rate of positive studies.", "contents": "Neuroradiology of the sphenoidal region. The neuroradiological techniques employed in diagnosing a series of 54 lesions involving the superior orbital fissure and cavernous sinus (sphenoidal region) were reviewed in order to compare the value of sphenoidal tomography, pneumoencephalography, cerebral arteriography and sphenoidal venography. The patients included in the series exhibited clinical syndromes of sphenoidal region cranial nerve deficits. Confirmation of the sphenoidal region disorder was obtained in all cases. Of the four procedures, sphenoidal venography and basal tomography yielded the highest rate of positive studies."} {"id": "PMID:164040", "title": "Polytomoencephalography of the optic chiasm and adjacent structures.", "content": "The addition of polytomography considerably increases the sensitivity of pneumoencephalography. The chiasmatic area lends itself particularly well to investigation by polytomoencephalography. In a series of 28 patients, the transverse dimension of the optic chiasm ranged from 4 to 20 mm, with a mean of 18 mm. The posterior portion of the chiasm tended to be U-shaped; its anterior portion's shape was that of a dumbbell. Intrachiasmatic tumors distort and enlarge the chiasm. The diaphragma sella is also particularly well evaluated by this technique. The study is safe, reliable, and can be repeated as needed.", "contents": "Polytomoencephalography of the optic chiasm and adjacent structures. The addition of polytomography considerably increases the sensitivity of pneumoencephalography. The chiasmatic area lends itself particularly well to investigation by polytomoencephalography. In a series of 28 patients, the transverse dimension of the optic chiasm ranged from 4 to 20 mm, with a mean of 18 mm. The posterior portion of the chiasm tended to be U-shaped; its anterior portion's shape was that of a dumbbell. Intrachiasmatic tumors distort and enlarge the chiasm. The diaphragma sella is also particularly well evaluated by this technique. The study is safe, reliable, and can be repeated as needed."} {"id": "PMID:164041", "title": "Results of postoperative megavoltage radiotherapy of malignant surface epithelial tumors of the ovary.", "content": "The results of postoperative radiotherapy in 151 patients with malignant epithelial tumors of the ovary are presented. Actuarial survival at five years for patients in FIGO Stage I was 76%; in Stage II, 56%; Stage III, 16%; and Stage IV, 0%. Survival also varied with histopathological type, the best prognoses occuring in the serous (malignant) and endometrioid types (NED survival of 35% and 50%, totalling all stages, respectively). The presence of ascites or intraperitoneal surgical spillage did not adversely affect survival. The role of lymphangiography in staging is discussed. New approaches to diagnosis, staging and treatment are required for improving the prognosis of patients with ovarian carcinoma.", "contents": "Results of postoperative megavoltage radiotherapy of malignant surface epithelial tumors of the ovary. The results of postoperative radiotherapy in 151 patients with malignant epithelial tumors of the ovary are presented. Actuarial survival at five years for patients in FIGO Stage I was 76%; in Stage II, 56%; Stage III, 16%; and Stage IV, 0%. Survival also varied with histopathological type, the best prognoses occuring in the serous (malignant) and endometrioid types (NED survival of 35% and 50%, totalling all stages, respectively). The presence of ascites or intraperitoneal surgical spillage did not adversely affect survival. The role of lymphangiography in staging is discussed. New approaches to diagnosis, staging and treatment are required for improving the prognosis of patients with ovarian carcinoma."} {"id": "PMID:164042", "title": "Conditioned medium from plateau-phase cells. Effect on growth of proliferative cells and on repair of potentially lethal radiation damage.", "content": "In vitro cell cultures grown into plateau phase may be more suitable than exponentially growing cells as a model for tumor cell growth in vivo. Conditioned medium extracted from cells in plateau phase inhibits growth of log-phase cultures of either the same or a different cell line. Attempts to demonstrate that this inhibition is due to a heat-labile diffusible substance have failed. Conditioned medium extracted from plateau-phase cultures was effective in enhancing repair of potentially lethal damage following x irradiation. Cell survival is significantly increased following a six-hour postirradiation culture in conditioned medium as opposed to complete fresh medium.", "contents": "Conditioned medium from plateau-phase cells. Effect on growth of proliferative cells and on repair of potentially lethal radiation damage. In vitro cell cultures grown into plateau phase may be more suitable than exponentially growing cells as a model for tumor cell growth in vivo. Conditioned medium extracted from cells in plateau phase inhibits growth of log-phase cultures of either the same or a different cell line. Attempts to demonstrate that this inhibition is due to a heat-labile diffusible substance have failed. Conditioned medium extracted from plateau-phase cultures was effective in enhancing repair of potentially lethal damage following x irradiation. Cell survival is significantly increased following a six-hour postirradiation culture in conditioned medium as opposed to complete fresh medium."} {"id": "PMID:164043", "title": "Idiopathic congenital hemihypertrophy with associated ipsilateral benign nephromegaly.", "content": "Two cases of idiopathic congenital hemihypertrophy with ipsilateral benign nephromegaly are presented. Excretory urography usually differentiates benign renal enlargement from Wilm's tumor in these patients. Angiography is indicated in equivocal cases. The clinical features, differential diagnosis, associated conditions, and importance of radiologic reevaluation in patients with hemihypertrophy are discussed.", "contents": "Idiopathic congenital hemihypertrophy with associated ipsilateral benign nephromegaly. Two cases of idiopathic congenital hemihypertrophy with ipsilateral benign nephromegaly are presented. Excretory urography usually differentiates benign renal enlargement from Wilm's tumor in these patients. Angiography is indicated in equivocal cases. The clinical features, differential diagnosis, associated conditions, and importance of radiologic reevaluation in patients with hemihypertrophy are discussed."} {"id": "PMID:164044", "title": "Fever, lethargy and rash complicating treatment for Wilms' tumor-a new syndrome?", "content": "A syndrome of fever, lethargy, irritability and rash occurred in patients undergoing surgery, irradiation and chemotherapy for Wilms' tumor. The incidence, course and severity of these findings are described. Potential etiologic factors are analyzed and a hypothesis advanced.", "contents": "Fever, lethargy and rash complicating treatment for Wilms' tumor-a new syndrome? A syndrome of fever, lethargy, irritability and rash occurred in patients undergoing surgery, irradiation and chemotherapy for Wilms' tumor. The incidence, course and severity of these findings are described. Potential etiologic factors are analyzed and a hypothesis advanced."} {"id": "PMID:164045", "title": "The hazards of myelography.", "content": "The history of myelography and reactions to various contrast media is reviewed. Air is completely absorbed without producing long-term side effects. Lipiodol and Pantopaque are not absorbed and residual medium in the spinal canal can cause arachnoiditis. Other agents as Diodrast and Thorotrast never gained widespread acceptance. The water-soluble Dimer-X and Conray 60 have come into prominence but they are not totally without reactions. Recently a new water-soluble nonionic contrast medium has been developed in Norway. Metrizamide (Amipaque) has the same overall density as other water-soluble media but produces fewer reactions.", "contents": "The hazards of myelography. The history of myelography and reactions to various contrast media is reviewed. Air is completely absorbed without producing long-term side effects. Lipiodol and Pantopaque are not absorbed and residual medium in the spinal canal can cause arachnoiditis. Other agents as Diodrast and Thorotrast never gained widespread acceptance. The water-soluble Dimer-X and Conray 60 have come into prominence but they are not totally without reactions. Recently a new water-soluble nonionic contrast medium has been developed in Norway. Metrizamide (Amipaque) has the same overall density as other water-soluble media but produces fewer reactions."} {"id": "PMID:164046", "title": "Computed tomography of liver specimens.", "content": "Fourteen liver specimens were studied by computed tomography with pathological correlation to evaluate the possible application of this technique to the diagnosis of hepatic lesions. Lesions were clearly demonstrated in 9 of 10 abnormal specimens, but differentiation among hepatomas, metastases, and cysts was not possible in vitro.", "contents": "Computed tomography of liver specimens. Fourteen liver specimens were studied by computed tomography with pathological correlation to evaluate the possible application of this technique to the diagnosis of hepatic lesions. Lesions were clearly demonstrated in 9 of 10 abnormal specimens, but differentiation among hepatomas, metastases, and cysts was not possible in vitro."} {"id": "PMID:164047", "title": "Angiographic signs of corpus callosal tumors: a reappraisal.", "content": "Angiographic findings of eleven corpus callosal tumors are analyzed. Three new angiographic signs are demonstration of the lateral ventricular roof veins, spreading of the septal veins, and actual demonstration of corpus callosal thickening. In contrast to traditional concepts, diagnostic abnormalities were angiographically demonstrated in all eleven cases. Biplane angiotomography is of vital importance in the angiographic diagnosis of this frequently subtle tumor.", "contents": "Angiographic signs of corpus callosal tumors: a reappraisal. Angiographic findings of eleven corpus callosal tumors are analyzed. Three new angiographic signs are demonstration of the lateral ventricular roof veins, spreading of the septal veins, and actual demonstration of corpus callosal thickening. In contrast to traditional concepts, diagnostic abnormalities were angiographically demonstrated in all eleven cases. Biplane angiotomography is of vital importance in the angiographic diagnosis of this frequently subtle tumor."} {"id": "PMID:164056", "title": "Zwoegerziekte virus, the causative agent for progressive interstitial pneumonia (maedi) and meningo-leucoencephalitis (visna) in sheep.", "content": "The final results of experimental infections with virus recovered from the lungs of sheep suffering from progressive interstitial pneumonia (=zwoegerziekte=maedi) are reported. The virus could be reisolated from blood samples of all experimentally infected sheep. Every animal produced antibodies against the virus. The neutralising, complement-fixing and precipitating antibodies remained present in the blood for six years. Fourteen out of 21 intrapulmonarily infected sheep developed clinical and/or histopathological lung lesions and in three a meningo-leucoencephalitis was detected in addition. One of these three developed the clinical and pathological signs of 'visna' 14 months after inoculation. Signs of visna were seen in eight of 10 sheep that had been inoculated intracerebrally. Furthermore, nine of these sheep suffered from progressive interstitial pneumonia. Hence the name maedi-visna virus is proposed for the agent which causes both disease entities. Three sheep that yielded virus after infection and in which antibodies were detected, did not develop histopathological lesions.", "contents": "Zwoegerziekte virus, the causative agent for progressive interstitial pneumonia (maedi) and meningo-leucoencephalitis (visna) in sheep. The final results of experimental infections with virus recovered from the lungs of sheep suffering from progressive interstitial pneumonia (=zwoegerziekte=maedi) are reported. The virus could be reisolated from blood samples of all experimentally infected sheep. Every animal produced antibodies against the virus. The neutralising, complement-fixing and precipitating antibodies remained present in the blood for six years. Fourteen out of 21 intrapulmonarily infected sheep developed clinical and/or histopathological lung lesions and in three a meningo-leucoencephalitis was detected in addition. One of these three developed the clinical and pathological signs of 'visna' 14 months after inoculation. Signs of visna were seen in eight of 10 sheep that had been inoculated intracerebrally. Furthermore, nine of these sheep suffered from progressive interstitial pneumonia. Hence the name maedi-visna virus is proposed for the agent which causes both disease entities. Three sheep that yielded virus after infection and in which antibodies were detected, did not develop histopathological lesions."} {"id": "PMID:164057", "title": "Some aspects of lipid metabolism in fatty liver and kidney syndrome in chicks.", "content": "Various aspects of lipid metabolism were examined in broiler chicks affected with fatty liver and kidney syndrome (FLKS). Plasma free fatty acid concentrations were invariably elevated. Plasma triglyceride concentrations were increased amounts of triglyceride-rich lipoproteins. Lipoprotein lipase activity in adipose tissue was considerably reduced, but in heart tissue the enzyme activity was increased. Hepatic lipogenesis was reduced. Rates of oxidation of palmitic and succinic acids by liver, heart and kidney were normal. The increased oxidation rate of palmitic acid following the addition of carnitine was also normal. These findings indicate that elevated blood lipid levels are likely to be an important factor contributing to the development of fatty deposition, particularly in extrahepatic tissues.", "contents": "Some aspects of lipid metabolism in fatty liver and kidney syndrome in chicks. Various aspects of lipid metabolism were examined in broiler chicks affected with fatty liver and kidney syndrome (FLKS). Plasma free fatty acid concentrations were invariably elevated. Plasma triglyceride concentrations were increased amounts of triglyceride-rich lipoproteins. Lipoprotein lipase activity in adipose tissue was considerably reduced, but in heart tissue the enzyme activity was increased. Hepatic lipogenesis was reduced. Rates of oxidation of palmitic and succinic acids by liver, heart and kidney were normal. The increased oxidation rate of palmitic acid following the addition of carnitine was also normal. These findings indicate that elevated blood lipid levels are likely to be an important factor contributing to the development of fatty deposition, particularly in extrahepatic tissues."} {"id": "PMID:164058", "title": "The relation between the rabbit potency test and the response of sheep to sheep clostridial vaccines.", "content": "Six commercially available clostridial vaccines comprising one oil-emulsion, two alum-precipitated and three aluminum hydroxide adjuvanted preparations, each containing between two and seven antigenic components, were administered to groups of 10 rabbits and eight sheep in accordance with manufacturers' recommendations. Serum antitoxic values to Cl welchii beta, Cl welchii epsilon, Cl septicum, Cl oedematins and Cl tetani toxins were determined 14 days after completion of each vaccination course. The overall pattern of mean antitoxic values was found to be similar in sheep and rabbits, a vaccine eliciting a comparatively high antibody titre to any given antigen component in sheep also inducing a comparatively high titre in the corresponding group of rabbits. Similarly, comparatively poor responses in sheep were associated with poor responses in rabbits. The degree of variation in response within groups of animals was greater in sheep than in rabbits for all five antigenic components assayed. Sheep consistently developed higher titres than rabbits to Cl oedematins component but consistently lower titres to both Cl welchii beta and epsilon components irrespective of the type of vaccine used. The response of both species to Cl tetani antigen was similar in terms of serum antitoxic values. It was concluded that rabbits provide a suitable model for the assessment of potency of sheep clostridial vaccines.", "contents": "The relation between the rabbit potency test and the response of sheep to sheep clostridial vaccines. Six commercially available clostridial vaccines comprising one oil-emulsion, two alum-precipitated and three aluminum hydroxide adjuvanted preparations, each containing between two and seven antigenic components, were administered to groups of 10 rabbits and eight sheep in accordance with manufacturers' recommendations. Serum antitoxic values to Cl welchii beta, Cl welchii epsilon, Cl septicum, Cl oedematins and Cl tetani toxins were determined 14 days after completion of each vaccination course. The overall pattern of mean antitoxic values was found to be similar in sheep and rabbits, a vaccine eliciting a comparatively high antibody titre to any given antigen component in sheep also inducing a comparatively high titre in the corresponding group of rabbits. Similarly, comparatively poor responses in sheep were associated with poor responses in rabbits. The degree of variation in response within groups of animals was greater in sheep than in rabbits for all five antigenic components assayed. Sheep consistently developed higher titres than rabbits to Cl oedematins component but consistently lower titres to both Cl welchii beta and epsilon components irrespective of the type of vaccine used. The response of both species to Cl tetani antigen was similar in terms of serum antitoxic values. It was concluded that rabbits provide a suitable model for the assessment of potency of sheep clostridial vaccines."} {"id": "PMID:164059", "title": "Insulin receptor: role in the resistance of human obesity to insulin.", "content": "Large adipocytes from obese subjects have similar receptor numbers and affinities for insulin as small adipocytes from subjects of normal weight. These results indicate that the insulin insensitivity of large fat cells from obese humans occurs after the insulin-receptor interaction and might be explained by either a dilution of receptors over the cell surface or by alterations in intracellular metabolism.", "contents": "Insulin receptor: role in the resistance of human obesity to insulin. Large adipocytes from obese subjects have similar receptor numbers and affinities for insulin as small adipocytes from subjects of normal weight. These results indicate that the insulin insensitivity of large fat cells from obese humans occurs after the insulin-receptor interaction and might be explained by either a dilution of receptors over the cell surface or by alterations in intracellular metabolism."} {"id": "PMID:164060", "title": "Induction of neural differentiation in cultures of amphibian undetermined presumptive epidermis by cyclic AMP derivatives.", "content": "Induction of neural differentiation in cultures of undetermined presumptive epidermis from three amphibian species was achieved by the addition of 1 millimolar dibutyryl adenosine 3',5'-monophosphate, 8-bromadenosine 3',5'-monophosphate, or adenosine C',E'-monophosphate together with theophylline. Adenosine 5'-monophosphate, adenosine 2',3'-monophosphate, dibutyryl guanosine 3',5'-monophosphate, and butyrate at 1 millimolar are ineffective. These results suggest that the action of the primary inductor or inductors may be mediated via adenosine 3',5'-monophosphate.", "contents": "Induction of neural differentiation in cultures of amphibian undetermined presumptive epidermis by cyclic AMP derivatives. Induction of neural differentiation in cultures of undetermined presumptive epidermis from three amphibian species was achieved by the addition of 1 millimolar dibutyryl adenosine 3',5'-monophosphate, 8-bromadenosine 3',5'-monophosphate, or adenosine C',E'-monophosphate together with theophylline. Adenosine 5'-monophosphate, adenosine 2',3'-monophosphate, dibutyryl guanosine 3',5'-monophosphate, and butyrate at 1 millimolar are ineffective. These results suggest that the action of the primary inductor or inductors may be mediated via adenosine 3',5'-monophosphate."} {"id": "PMID:164061", "title": "The lamellar substructure of osmiophilic inclusion bodies present in rat type II alveolar pneumonocytes.", "content": "When rat pulmonary tissues are processed as outlined in this paper, the type II cell's surfactant containing osmiophilic inclusion bodies possess a periodic substructure. This substructure consists of electron-opaque lamellae, 26 A in thickness alternating with 16 A wide electron-translucent zones.", "contents": "The lamellar substructure of osmiophilic inclusion bodies present in rat type II alveolar pneumonocytes. When rat pulmonary tissues are processed as outlined in this paper, the type II cell's surfactant containing osmiophilic inclusion bodies possess a periodic substructure. This substructure consists of electron-opaque lamellae, 26 A in thickness alternating with 16 A wide electron-translucent zones."} {"id": "PMID:164062", "title": "The inhibitive effects of steroid analogues in the binding of tritiated 5alpha-dihydrotestosterone to receptor proteins from rat prostate tissue.", "content": "The relationship between molecular structure and the binding potential of steroids to receptor proteins was investigated. Twenty-four selected steroids were studied in minced incubations of rat prostate tissue. Measurements of the inhibitory effects of the steroids on the binding of tritiated 5alpha-dihydrotestosterone to the receptor proteins were obtained in the 100,000 times g dialysed supernatant and the purified nuclear component of the prostate cells. The steroids that achieved the highest degree of inhibition were those compounds that exhibited a generally planar geometric shape and were known to possess potent androgenic activity. Several of the compounds were shown to possess a higher degree of inhibition than that of testosterone or 5alpha-dihydrotestosterone. The data is further supportive of the two step theory that necessitates the complexing of the free steroids to the receptor proteins in the cytosol before transport to the nuclei. Evidence is also suggestive of the presence of 17-esterase activity. The inhibitory effect of the steroids apparently involves the binding to the intracellular receptors and is not related to the uptake of 5alpha-dihydrotestosterone into the cell.", "contents": "The inhibitive effects of steroid analogues in the binding of tritiated 5alpha-dihydrotestosterone to receptor proteins from rat prostate tissue. The relationship between molecular structure and the binding potential of steroids to receptor proteins was investigated. Twenty-four selected steroids were studied in minced incubations of rat prostate tissue. Measurements of the inhibitory effects of the steroids on the binding of tritiated 5alpha-dihydrotestosterone to the receptor proteins were obtained in the 100,000 times g dialysed supernatant and the purified nuclear component of the prostate cells. The steroids that achieved the highest degree of inhibition were those compounds that exhibited a generally planar geometric shape and were known to possess potent androgenic activity. Several of the compounds were shown to possess a higher degree of inhibition than that of testosterone or 5alpha-dihydrotestosterone. The data is further supportive of the two step theory that necessitates the complexing of the free steroids to the receptor proteins in the cytosol before transport to the nuclei. Evidence is also suggestive of the presence of 17-esterase activity. The inhibitory effect of the steroids apparently involves the binding to the intracellular receptors and is not related to the uptake of 5alpha-dihydrotestosterone into the cell."} {"id": "PMID:164063", "title": "The urinary metabolites of 17alpha-ethynylestradiol-9alpha,11xi-3H in women. Chromatographic profiling and indentification of ethynyl and non-ethynyl compounds.", "content": "Metabolites of 17alpha-ethynylestradiol (EE2) were obtained from human urine following ingestion of tritium-labeled EE2. Over 95% of the recovered activity was found as conjugated steroids and these were separated into four groups by chromatography of the urine extract on Sephadex LH-20 with chloroform-methanol (1/1) + 0.01M NaCl. The two major conjugate fractions appeared to be almost exclusively glucosiduronates. Enzymatic hydrolysis liberated at least ten different EE2 metabolites as shown by chromatography on Sephadex LH-20 with benzene-methanol (85/15). After additional separation and purification of these metabolites, positive identification was obtained for nine radioactive compounds by either gas liquid chromatography-mass spectrometry or reverse-isotope recrystallization. Five were ethynyl compounds: EE2, 2-MeO EE2, 16beta-OH EE2, 2-OH EE2 and 6alpha-OH EE2. The other four were de-ethynylated estrogens: estrone, estradiol-17beta, estriol, and 2-Me-O-estradiol-17beta.", "contents": "The urinary metabolites of 17alpha-ethynylestradiol-9alpha,11xi-3H in women. Chromatographic profiling and indentification of ethynyl and non-ethynyl compounds. Metabolites of 17alpha-ethynylestradiol (EE2) were obtained from human urine following ingestion of tritium-labeled EE2. Over 95% of the recovered activity was found as conjugated steroids and these were separated into four groups by chromatography of the urine extract on Sephadex LH-20 with chloroform-methanol (1/1) + 0.01M NaCl. The two major conjugate fractions appeared to be almost exclusively glucosiduronates. Enzymatic hydrolysis liberated at least ten different EE2 metabolites as shown by chromatography on Sephadex LH-20 with benzene-methanol (85/15). After additional separation and purification of these metabolites, positive identification was obtained for nine radioactive compounds by either gas liquid chromatography-mass spectrometry or reverse-isotope recrystallization. Five were ethynyl compounds: EE2, 2-MeO EE2, 16beta-OH EE2, 2-OH EE2 and 6alpha-OH EE2. The other four were de-ethynylated estrogens: estrone, estradiol-17beta, estriol, and 2-Me-O-estradiol-17beta."} {"id": "PMID:164064", "title": "Androgen-induced nuclear accumulation of the estrogen receptor.", "content": "The effect of androgens on the nuclear uptake of both tritiated estradiol (3H-E2) and the estrogen receptor was studied in immature rat uteri. It was demonstrated that in vitro preincubation of immature rat uteri with various androgens (1 muM to 50 muM) followed by incubation with 3H-E2 (20 nM) resulted in a greatly decreased specific nuclear uptake of 3H-E2. Non-androgenic steroids had no effect. It was also confirmed that 5alpha-dihydrotestosterone (DHT) causes the accumulation of the estrogen receptor in the nuclei of uterine tissue. In vitro incubations of rat uteri with DHT (1muM and 50muM) were found to cause maximal nuclear estrogen receptor accumulation to the same degree as caused by estradiol, i.e. the nuclear uptake of approximately 100% of the estrogen receptor. Antiandrogens, which block the binding of androgens to the testosterone receptor in various tissues, did not inhibit the DHT - induced decrease in the 3H-E2 uptake by the uterine nuclei or the DHT - caused accumulation of the estrogen receptor in nuclei. These results seem to indicate that the uterine testosterone receptor has no role in the androgen - induced nuclear uptake of the estrogen receptor. However, the non-steroidal antiestrogens inhibited the DHT - induced nuclear accumulation of the estrogen receptor. This would seem to indicate that the estrogen - and androgen - induced nuclear accumulation of the estrogen receptor share a common mechanism.", "contents": "Androgen-induced nuclear accumulation of the estrogen receptor. The effect of androgens on the nuclear uptake of both tritiated estradiol (3H-E2) and the estrogen receptor was studied in immature rat uteri. It was demonstrated that in vitro preincubation of immature rat uteri with various androgens (1 muM to 50 muM) followed by incubation with 3H-E2 (20 nM) resulted in a greatly decreased specific nuclear uptake of 3H-E2. Non-androgenic steroids had no effect. It was also confirmed that 5alpha-dihydrotestosterone (DHT) causes the accumulation of the estrogen receptor in the nuclei of uterine tissue. In vitro incubations of rat uteri with DHT (1muM and 50muM) were found to cause maximal nuclear estrogen receptor accumulation to the same degree as caused by estradiol, i.e. the nuclear uptake of approximately 100% of the estrogen receptor. Antiandrogens, which block the binding of androgens to the testosterone receptor in various tissues, did not inhibit the DHT - induced decrease in the 3H-E2 uptake by the uterine nuclei or the DHT - caused accumulation of the estrogen receptor in nuclei. These results seem to indicate that the uterine testosterone receptor has no role in the androgen - induced nuclear uptake of the estrogen receptor. However, the non-steroidal antiestrogens inhibited the DHT - induced nuclear accumulation of the estrogen receptor. This would seem to indicate that the estrogen - and androgen - induced nuclear accumulation of the estrogen receptor share a common mechanism."} {"id": "PMID:164069", "title": "[Membrane antigens of Zajdela ascitic hepatoma].", "content": "The membrane antigens of Zajdela ascitic hepatoma cells were investigated. Living cells were studied by immunofluorescence method, and solublized membrane preparations by the precipitation reacting in agar gel. Testing of the tumor cells with organospecific anti-kidney serum caused a specific fluorescence of tumor cells surface. This can be due to incorporation into the antigenic structure of the Zajdela hepatoma cell membranes of at least one organospecific antigen. Treatment of the tumor cells with organospecific anti-liver serum led to specific fluorescence of tumor cells surface. In solubilizates of the tumor cells one of the three organospecific antigens peculiar for the normal liver cells, was detected.", "contents": "[Membrane antigens of Zajdela ascitic hepatoma]. The membrane antigens of Zajdela ascitic hepatoma cells were investigated. Living cells were studied by immunofluorescence method, and solublized membrane preparations by the precipitation reacting in agar gel. Testing of the tumor cells with organospecific anti-kidney serum caused a specific fluorescence of tumor cells surface. This can be due to incorporation into the antigenic structure of the Zajdela hepatoma cell membranes of at least one organospecific antigen. Treatment of the tumor cells with organospecific anti-liver serum led to specific fluorescence of tumor cells surface. In solubilizates of the tumor cells one of the three organospecific antigens peculiar for the normal liver cells, was detected."} {"id": "PMID:164070", "title": "[Quantitative changes in proteins in the cat parietal zone large pyramids in various sleep stages and during wakefulness].", "content": "Protein content in large pyramidal cells of the parietal cortex was shown to be by 28.9% lesser during the slow--wave sleep than during the paradoxical sleep.", "contents": "[Quantitative changes in proteins in the cat parietal zone large pyramids in various sleep stages and during wakefulness]. Protein content in large pyramidal cells of the parietal cortex was shown to be by 28.9% lesser during the slow--wave sleep than during the paradoxical sleep."} {"id": "PMID:164071", "title": "[Electron microscopic and electron histochemical study of mitochondrial inclusions in insect intestine epithelial cells].", "content": "The electron microscope investigation of the midgut epithelial cells of Chaoborus obscuripes revealed special membrane formations in mitochondria. The mitochondrial inclusions (MI) look like small membranous whorls about 0.2--0.3 microns in diameter. In a certain period of functional activity, MI start leaving the mitochondria and appear in cytoplasm. Later, large multimembrane structures (MS) composed of parallel membranes in concentric or whorl--like arrangement are observed in the cytoplasm. At first MS are situated in the vicinity of mitochondria, then they gather near the base of the villus. The relationship between appearance of MI and MS in the cytoplasm and the digestion process was revealed. Treatment of ultrathin sections with H202 or H5J06 showed MI and MS to be composed mainly of lipids. This suggests that MI and MS,probably, take part in the lipids metabolism of the midgut epithelial cells of insect.", "contents": "[Electron microscopic and electron histochemical study of mitochondrial inclusions in insect intestine epithelial cells]. The electron microscope investigation of the midgut epithelial cells of Chaoborus obscuripes revealed special membrane formations in mitochondria. The mitochondrial inclusions (MI) look like small membranous whorls about 0.2--0.3 microns in diameter. In a certain period of functional activity, MI start leaving the mitochondria and appear in cytoplasm. Later, large multimembrane structures (MS) composed of parallel membranes in concentric or whorl--like arrangement are observed in the cytoplasm. At first MS are situated in the vicinity of mitochondria, then they gather near the base of the villus. The relationship between appearance of MI and MS in the cytoplasm and the digestion process was revealed. Treatment of ultrathin sections with H202 or H5J06 showed MI and MS to be composed mainly of lipids. This suggests that MI and MS,probably, take part in the lipids metabolism of the midgut epithelial cells of insect."} {"id": "PMID:164075", "title": "[Benign non-epithelial tumors of the stomach].", "content": "Data relative to 36 patients with benign gastric tumors of various histological structure have been studied. The clinical picture, methods of diagnosis and operative technic wwere discussed. Based on the author's personal data a conslusion is drawn on the possibility of a preoperative diagnosis of benign non-epithelial tumors of the stomach and indications to dissection of a tumor instead of gastric resection.", "contents": "[Benign non-epithelial tumors of the stomach]. Data relative to 36 patients with benign gastric tumors of various histological structure have been studied. The clinical picture, methods of diagnosis and operative technic wwere discussed. Based on the author's personal data a conslusion is drawn on the possibility of a preoperative diagnosis of benign non-epithelial tumors of the stomach and indications to dissection of a tumor instead of gastric resection."} {"id": "PMID:164087", "title": "Effects of proteases and neuraminidase on RBC surface charge and agglutination. A kinetic study.", "content": "Electrophoretic mobility, membrane sialic acid content and agglutinability by \"incomplete\" antisera against Rh-o, hr' and k antigens were determined for red blood cells in the course of treatment with trypsin, ficin and neuraminidase. Neuraminidase gradually produces a slight to moderate agglutinability as it reduced surface charge density in proportion to the amount of sialic acid removed. Proteases acted in two distinct steps. The first stage is characterized by the cells rapidly becoming highly agglutinable and by the unmasking of new negative charge as the first half of the sialic acid is removed. In the second stage the cells show a slight gain in agglutinability as surface charge is removed in proportion to sialic acid removal as in the case of neuraminidase. Neuraminidase-treated cells are considerably less agglutinable than cells reduced to the same zeta-potential by protease treatment. The greater efficacy of proteases compared to neuraminidase in making cells agglutinable could be because they not only reduce surface charge density but also increase antigen-antibody bond strength, render antigens more mobile in the membrane to allow clustering in regions of cell to cell antibody bridging and remove glycopeptide chains which may be causing steric hindrance to antigen-antibody binding or to cell-cell contact.", "contents": "Effects of proteases and neuraminidase on RBC surface charge and agglutination. A kinetic study. Electrophoretic mobility, membrane sialic acid content and agglutinability by \"incomplete\" antisera against Rh-o, hr' and k antigens were determined for red blood cells in the course of treatment with trypsin, ficin and neuraminidase. Neuraminidase gradually produces a slight to moderate agglutinability as it reduced surface charge density in proportion to the amount of sialic acid removed. Proteases acted in two distinct steps. The first stage is characterized by the cells rapidly becoming highly agglutinable and by the unmasking of new negative charge as the first half of the sialic acid is removed. In the second stage the cells show a slight gain in agglutinability as surface charge is removed in proportion to sialic acid removal as in the case of neuraminidase. Neuraminidase-treated cells are considerably less agglutinable than cells reduced to the same zeta-potential by protease treatment. The greater efficacy of proteases compared to neuraminidase in making cells agglutinable could be because they not only reduce surface charge density but also increase antigen-antibody bond strength, render antigens more mobile in the membrane to allow clustering in regions of cell to cell antibody bridging and remove glycopeptide chains which may be causing steric hindrance to antigen-antibody binding or to cell-cell contact."} {"id": "PMID:164083", "title": "[Determination of carboxycathepsin (peptidyl dipeptidase) activity in human blood serum].", "content": "Based on fluorometric determination of a dipeptide histidil-leucine, which is splitted off from a synthetic substrate (Cbz-Phe-His-Leu) by carboxycathepsin (carboxydipeptidyl peptide hydrolase), a method was developed for estimation of the enzymatic activity in human blood serum. The method is characterized by simplicity and high sensitivity; Use of small amount of blood serum (about 0.03 ml) was possible. In normal human blood serum the carboxycathepsin activity varied from 7.5 to 18 nmoles of the dipeptide, liberated per mg of protein per hr.", "contents": "[Determination of carboxycathepsin (peptidyl dipeptidase) activity in human blood serum]. Based on fluorometric determination of a dipeptide histidil-leucine, which is splitted off from a synthetic substrate (Cbz-Phe-His-Leu) by carboxycathepsin (carboxydipeptidyl peptide hydrolase), a method was developed for estimation of the enzymatic activity in human blood serum. The method is characterized by simplicity and high sensitivity; Use of small amount of blood serum (about 0.03 ml) was possible. In normal human blood serum the carboxycathepsin activity varied from 7.5 to 18 nmoles of the dipeptide, liberated per mg of protein per hr."} {"id": "PMID:164092", "title": "The relative roles of iodination and iodothyronine content on thyroglobulin stability.", "content": "We have independently varied the degree of iodination and of iodothyronine formation over a wide range by acutely administering various doses of perchlorate and/or methimazole to severely iodine-deficient rats 30 min before giving 131-I- with graded quantities (1-100 mug of 127-I-). Thyroids were removed 4 h later and the soluble protein analyzed for labelled iodoamino acid composition and with sucrose density gradient ultracentrifugation. Since the total thyroid iodine content before administering 127I- was less than 1 mug, calculation of the degree of iodination and iodothyronine content of the labelled Tgb could be made from the known specificity of the injected labelled iodide. Newly organified iodine ranged from smaller than 0.1 to 1.4 mug/thyroid and labelled iodothyronines from smaller than 5 to 962 pmoles/thyroid. Both the degree of iodination and iodothyronine content varied directly with Tgb stability in the absence of inhibitors. But when Tgb iodination was kept constant, Tgb stability at pH 10.1 varied directly with iodothyronine content. When iodothyronine content was kept constant, Tgb stability was independent of the degree of iodination. Correlation of stability with iodothyronine content was highly significant (r=0.79, Psmaller than 0.001) but not of stability with iodine content (r=0.49, P larger than 0.05). We conclude that the primary determinant of Tgb stability in mild alkali is the iodothyronine content and not the degree of iodination of the protein. The increased Tgb stability may be induced by coupling between iodotyrosil residues of different 12 S subunits rather than between residues of the same 12 S subunit.", "contents": "The relative roles of iodination and iodothyronine content on thyroglobulin stability. We have independently varied the degree of iodination and of iodothyronine formation over a wide range by acutely administering various doses of perchlorate and/or methimazole to severely iodine-deficient rats 30 min before giving 131-I- with graded quantities (1-100 mug of 127-I-). Thyroids were removed 4 h later and the soluble protein analyzed for labelled iodoamino acid composition and with sucrose density gradient ultracentrifugation. Since the total thyroid iodine content before administering 127I- was less than 1 mug, calculation of the degree of iodination and iodothyronine content of the labelled Tgb could be made from the known specificity of the injected labelled iodide. Newly organified iodine ranged from smaller than 0.1 to 1.4 mug/thyroid and labelled iodothyronines from smaller than 5 to 962 pmoles/thyroid. Both the degree of iodination and iodothyronine content varied directly with Tgb stability in the absence of inhibitors. But when Tgb iodination was kept constant, Tgb stability at pH 10.1 varied directly with iodothyronine content. When iodothyronine content was kept constant, Tgb stability was independent of the degree of iodination. Correlation of stability with iodothyronine content was highly significant (r=0.79, Psmaller than 0.001) but not of stability with iodine content (r=0.49, P larger than 0.05). We conclude that the primary determinant of Tgb stability in mild alkali is the iodothyronine content and not the degree of iodination of the protein. The increased Tgb stability may be induced by coupling between iodotyrosil residues of different 12 S subunits rather than between residues of the same 12 S subunit."} {"id": "PMID:164093", "title": "Regulation of plasma oestrogens in normal adult males. II. Response of oestradiol, oestrone, testosterone and cortisol to dexamethasone and ACTH administration.", "content": "The response of plasma oestradiol (Oe-2), oestrone (Oe-1), testosterone (T) and cortisol to dexamethasone and ACTH administration in normal adult males was ascertained. After an oral dose of 1.5 mg dexamethasone Oe-1 decreased from 2. 51 to 1.85 ng/100 ml (74% of the control level, mean of 15 subjects) over night and after continuing the dexamethasone administration for two more days (twice daily 1.5 mg) Oe-1 decreased to 1.30 ng/100 ml (52%). Oe-2 (control level 1.71 ng/100 ml) and T (678 ng/100 ml) did not change over night, but at the end of the test Oe-2 decreased to 84% and T to 91% of the control level. After a single im injection of 2 mg beta 1-24 cortrophin Oe-1 increased 1.9 times (meanof 13 subjects) without further increase during two more days of treatment (twice daily 1 mg), while Oe-2 did not change over night and decreased to 75% of the control level at the end of the test. Under ACTH T decreased to 66% of the control level over night and to 50% at the end of the test indicating a suppression of the testicular hormone secretion. From these results and those reported previously it was concluded that the testicular hormone secretion influences mainly Oe-2 in peripheral plasma, while Oe-1 depends mainly on the adrenal hormone secretion.", "contents": "Regulation of plasma oestrogens in normal adult males. II. Response of oestradiol, oestrone, testosterone and cortisol to dexamethasone and ACTH administration. The response of plasma oestradiol (Oe-2), oestrone (Oe-1), testosterone (T) and cortisol to dexamethasone and ACTH administration in normal adult males was ascertained. After an oral dose of 1.5 mg dexamethasone Oe-1 decreased from 2. 51 to 1.85 ng/100 ml (74% of the control level, mean of 15 subjects) over night and after continuing the dexamethasone administration for two more days (twice daily 1.5 mg) Oe-1 decreased to 1.30 ng/100 ml (52%). Oe-2 (control level 1.71 ng/100 ml) and T (678 ng/100 ml) did not change over night, but at the end of the test Oe-2 decreased to 84% and T to 91% of the control level. After a single im injection of 2 mg beta 1-24 cortrophin Oe-1 increased 1.9 times (meanof 13 subjects) without further increase during two more days of treatment (twice daily 1 mg), while Oe-2 did not change over night and decreased to 75% of the control level at the end of the test. Under ACTH T decreased to 66% of the control level over night and to 50% at the end of the test indicating a suppression of the testicular hormone secretion. From these results and those reported previously it was concluded that the testicular hormone secretion influences mainly Oe-2 in peripheral plasma, while Oe-1 depends mainly on the adrenal hormone secretion."} {"id": "PMID:164094", "title": "Progesterone-binding proteins: in vitro binding and biological activity of different steroidal ligands.", "content": "Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied. In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy. The binding energies of the well bound progestational compounds were of the order of -12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl sid chain each contributed-3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17alpha-ethynyl-17beta-hydroxyl function could replace the acetyl side chain. For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far asthe binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response.", "contents": "Progesterone-binding proteins: in vitro binding and biological activity of different steroidal ligands. Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied. In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy. The binding energies of the well bound progestational compounds were of the order of -12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl sid chain each contributed-3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17alpha-ethynyl-17beta-hydroxyl function could replace the acetyl side chain. For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far asthe binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response."} {"id": "PMID:164088", "title": "[Synthesis and properties of 5-acetyl-4-methyl-1-(beta-d-ribofuranosyl)-imidazole-5' di-and-triphosphate].", "content": "5-Acetyl-4-methyl-1-(beta-D-ribofuranosyl)-imidazole-5'-phosphate reacts with diphenylphospho chloridate forming the asymmetrical pyrophosphate ester. This in turn reacts with tri-n-butyl-ammonium phosphate yielding 5-acetyl-4-methyl-imidazole-riboside-5'-diphosphate and with tri-n-butylammonium pyrophosphate to give the nucleotide triphosphate. 5-Acetyl-4-methyl-imidazole-riboside-5'-pyrophosphate shows in the test with pyruvate kinase a reaction rate three times slower than that of ADP; but the same Km as that of ADP. The ATP analogue is only about 10% as effective as ATP itself in the test with hexokinase, 3-phosphoglycerate kinase and gloconate kinase. Adenylate kinase and NAD\" kinase show no activity when ATP is replaced by the nucleotide-triphosphate-analogue. In presence of ATP the analogue strongly inhibits the reaction of adenylate kinase.", "contents": "[Synthesis and properties of 5-acetyl-4-methyl-1-(beta-d-ribofuranosyl)-imidazole-5' di-and-triphosphate]. 5-Acetyl-4-methyl-1-(beta-D-ribofuranosyl)-imidazole-5'-phosphate reacts with diphenylphospho chloridate forming the asymmetrical pyrophosphate ester. This in turn reacts with tri-n-butyl-ammonium phosphate yielding 5-acetyl-4-methyl-imidazole-riboside-5'-diphosphate and with tri-n-butylammonium pyrophosphate to give the nucleotide triphosphate. 5-Acetyl-4-methyl-imidazole-riboside-5'-pyrophosphate shows in the test with pyruvate kinase a reaction rate three times slower than that of ADP; but the same Km as that of ADP. The ATP analogue is only about 10% as effective as ATP itself in the test with hexokinase, 3-phosphoglycerate kinase and gloconate kinase. Adenylate kinase and NAD\" kinase show no activity when ATP is replaced by the nucleotide-triphosphate-analogue. In presence of ATP the analogue strongly inhibits the reaction of adenylate kinase."} {"id": "PMID:164085", "title": "[Change in the glycolytic and glucose-6-phosphate dehydrogenase activity in experimental cirrhosis of the liver].", "content": "Development of cirrhosis of liver tissue did not influence the intensity of glycolysis, with glucose as a substrate, in supernatant fraction of liver homogenate in chronic intoxication with CCL4. In preparations of cirrhotic liver, as compared with liver from the intact animals, more distinct activation of glycolysis was caused by addition of ATP and NAD at the stage of 3-week intoxication and also by addition of hexokinase, glyceraldehydephosphate dehydrogenase and lactate dehydrogenase at the stage of distinct cirrhosis of liver (6 weeks of CCL4 intoxication). Km values for glucose-6-phosphate dehydrogenase increased over all the periods of intoxication.", "contents": "[Change in the glycolytic and glucose-6-phosphate dehydrogenase activity in experimental cirrhosis of the liver]. Development of cirrhosis of liver tissue did not influence the intensity of glycolysis, with glucose as a substrate, in supernatant fraction of liver homogenate in chronic intoxication with CCL4. In preparations of cirrhotic liver, as compared with liver from the intact animals, more distinct activation of glycolysis was caused by addition of ATP and NAD at the stage of 3-week intoxication and also by addition of hexokinase, glyceraldehydephosphate dehydrogenase and lactate dehydrogenase at the stage of distinct cirrhosis of liver (6 weeks of CCL4 intoxication). Km values for glucose-6-phosphate dehydrogenase increased over all the periods of intoxication."} {"id": "PMID:164095", "title": "Progesterone-binding proteins from endometrium and myometrium of sheep uterus: a comparative study.", "content": "The binding of tritiated proesterone to the cytoplasmic progestogen receptors from oestrogen-primed sheep endometrium and myometrium has been investigated. The binding characteristics of the progesterone receptors from both sources were determined in the supernatant fractions obtained after high speed centrifugation of the myometrial and endometrial homogenates. High affinity binding proteins with identical association constants for progesterone (1 times 10-9 M-1) were detected in both endometrium and myometrium. The concentration of binding sites was also of the same order of magnitude in both tissues. After centrifugation on surcrose gradients, these binding proteins were shown to have similar sedimentation constants, 7S in a gradient containing no added KC1 and 4S in a gradient containing 0.4 M KC1. The binding peaks from both sources could be abolished by heating the cytosol at 60 degrees C for half an hour. The proteinaceous nature of the binding materials was demonstrated by incubation of the endometrial and myometrial cytosols with pronase, DNase and RNase: the binding was totally eliminated by the proteolytic action of pronase whereas DNase and RNase had no effect. The ligand specificity of the two progesterone binding proteins was studied using a competitive protein-binding technique. Both the endometrial and the myometrial receptor proteins were shown to bind only steroids which are known potent progestogens. In addition, the relative affinities of the binding proteins for 37 steroidal compounds closely resembled each other. Thus, the physiochemical and binding data obtained show that a very close similarity exists between the progesterone-binding proteins in the endometrium and myometrium of ovariectomized sheep after oestradiol treatment.", "contents": "Progesterone-binding proteins from endometrium and myometrium of sheep uterus: a comparative study. The binding of tritiated proesterone to the cytoplasmic progestogen receptors from oestrogen-primed sheep endometrium and myometrium has been investigated. The binding characteristics of the progesterone receptors from both sources were determined in the supernatant fractions obtained after high speed centrifugation of the myometrial and endometrial homogenates. High affinity binding proteins with identical association constants for progesterone (1 times 10-9 M-1) were detected in both endometrium and myometrium. The concentration of binding sites was also of the same order of magnitude in both tissues. After centrifugation on surcrose gradients, these binding proteins were shown to have similar sedimentation constants, 7S in a gradient containing no added KC1 and 4S in a gradient containing 0.4 M KC1. The binding peaks from both sources could be abolished by heating the cytosol at 60 degrees C for half an hour. The proteinaceous nature of the binding materials was demonstrated by incubation of the endometrial and myometrial cytosols with pronase, DNase and RNase: the binding was totally eliminated by the proteolytic action of pronase whereas DNase and RNase had no effect. The ligand specificity of the two progesterone binding proteins was studied using a competitive protein-binding technique. Both the endometrial and the myometrial receptor proteins were shown to bind only steroids which are known potent progestogens. In addition, the relative affinities of the binding proteins for 37 steroidal compounds closely resembled each other. Thus, the physiochemical and binding data obtained show that a very close similarity exists between the progesterone-binding proteins in the endometrium and myometrium of ovariectomized sheep after oestradiol treatment."} {"id": "PMID:164096", "title": "Plasma testosterone in Klinefelter's syndrome: diurnal variation and response to ACTH and dexamethasone.", "content": "The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude. Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome.", "contents": "Plasma testosterone in Klinefelter's syndrome: diurnal variation and response to ACTH and dexamethasone. The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude. Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome."} {"id": "PMID:164099", "title": "Viral infection and psychiatric disorders.", "content": "A psychiatric population of 94 inpatients and 12 outpatients was investigated on referral to a psychiatric unit in a general hospital for serum antibody titres to several viruses by a complement fixation technique. Of the total population studied, only eight were considered to have antibody titres of possible significance. This result would appear to indicate that viral infection does not play a major part in the causation or precipitation of psychiatric disorders.", "contents": "Viral infection and psychiatric disorders. A psychiatric population of 94 inpatients and 12 outpatients was investigated on referral to a psychiatric unit in a general hospital for serum antibody titres to several viruses by a complement fixation technique. Of the total population studied, only eight were considered to have antibody titres of possible significance. This result would appear to indicate that viral infection does not play a major part in the causation or precipitation of psychiatric disorders."} {"id": "PMID:164101", "title": "Characteristics of proliferative cells from young, old, and transformed WI 38 cultures.", "content": "Mitotic cells were obtained by a shake off procedure from cultures of normal WI 38 cells at various passage levels, and from SV-40 virus transformed cells. The size of all mitotic WI 38 cells was similar regardless of in vitro age, whereas cells from the monolayer displayed an age-related increase in size. Mitotic transformed cells were similar to normal in size, but no size changes were observed in transformed monolayer cells during serial passage. Ultrastructural studies of mitotic WI 38 cells revealed no consistent change in the numbers of mitochondria or lysosome-like bodies during aging in culture. Mitotic transformed cells displayed numbers of mitochondria comparable to normal cells, but lysosome-like bodies occurred less frequently. Size distribution and structural characteristic are presented in relation to the ability of cells to synthesize DNA and to divide. These results support the contention that aging in WI 38 cultures is characterized by a declining fraction of homogeneous, actively dividing cells, and an increasing fraction of heterogenous nondividers that display senescent changes.", "contents": "Characteristics of proliferative cells from young, old, and transformed WI 38 cultures. Mitotic cells were obtained by a shake off procedure from cultures of normal WI 38 cells at various passage levels, and from SV-40 virus transformed cells. The size of all mitotic WI 38 cells was similar regardless of in vitro age, whereas cells from the monolayer displayed an age-related increase in size. Mitotic transformed cells were similar to normal in size, but no size changes were observed in transformed monolayer cells during serial passage. Ultrastructural studies of mitotic WI 38 cells revealed no consistent change in the numbers of mitochondria or lysosome-like bodies during aging in culture. Mitotic transformed cells displayed numbers of mitochondria comparable to normal cells, but lysosome-like bodies occurred less frequently. Size distribution and structural characteristic are presented in relation to the ability of cells to synthesize DNA and to divide. These results support the contention that aging in WI 38 cultures is characterized by a declining fraction of homogeneous, actively dividing cells, and an increasing fraction of heterogenous nondividers that display senescent changes."} {"id": "PMID:164102", "title": "The effect of age on mitochondrial ultrastructure and enzymes.", "content": "The ultrastructure of perfused livers and of mitochondrial fractions from 6 months and 30 month-old C57/BL mice were studied. In old mice the liver cell mitochondria were enlarged and rounded with a light \"foamy\", vacuolated matrix, short cristae and a loss of dense granules. Quantitative studies showed a 60% increase in the mean size and an increased proportion of larger mitochondria in intact 30 month-old perfused livers. Endothelial and Kupffer cell mitochondria were smaller than those of the parenchymal cells. Mitochondria in pellets prepared from 6 and 30 month-old livers were rounded and condensed although there were a few larger and \"foamy\" mitochondria in the preparations from old mice. Up to 47% of large mitochondria in the old livers were lost during cell fractionation. The levels of cytochrome oxidase and malate dehydrogenase were slightly decreased with age but their cytochemical localization was unchanged.", "contents": "The effect of age on mitochondrial ultrastructure and enzymes. The ultrastructure of perfused livers and of mitochondrial fractions from 6 months and 30 month-old C57/BL mice were studied. In old mice the liver cell mitochondria were enlarged and rounded with a light \"foamy\", vacuolated matrix, short cristae and a loss of dense granules. Quantitative studies showed a 60% increase in the mean size and an increased proportion of larger mitochondria in intact 30 month-old perfused livers. Endothelial and Kupffer cell mitochondria were smaller than those of the parenchymal cells. Mitochondria in pellets prepared from 6 and 30 month-old livers were rounded and condensed although there were a few larger and \"foamy\" mitochondria in the preparations from old mice. Up to 47% of large mitochondria in the old livers were lost during cell fractionation. The levels of cytochrome oxidase and malate dehydrogenase were slightly decreased with age but their cytochemical localization was unchanged."} {"id": "PMID:164104", "title": "Viral infection and interferon in cell cultures aged in vitro.", "content": "Cells from leucosis-free chick embryos (skin and muscles), grown in vitro 1 and 7 days with no medium change, are used as a model for young dividing and stationary in vitro aged cells, respectively. Aged cultures are advantageous for IF induction by cytopathic and noncytopathic viruses. Decreased virus production in them is ascribed to a back effect of the early formed IF onto the inducing virus. A factor which stimulates viral IF interferon induction also in young cultures, is released from aged cells into the medium. This factor could belong -- according to its properties and action -- into the class of chalones.", "contents": "Viral infection and interferon in cell cultures aged in vitro. Cells from leucosis-free chick embryos (skin and muscles), grown in vitro 1 and 7 days with no medium change, are used as a model for young dividing and stationary in vitro aged cells, respectively. Aged cultures are advantageous for IF induction by cytopathic and noncytopathic viruses. Decreased virus production in them is ascribed to a back effect of the early formed IF onto the inducing virus. A factor which stimulates viral IF interferon induction also in young cultures, is released from aged cells into the medium. This factor could belong -- according to its properties and action -- into the class of chalones."} {"id": "PMID:164105", "title": "Ultrastructure of in vitro aged chick embryo cell cultures in relation to viral infection.", "content": "The ultrastructure of young uninfected and infected with herpes simplex virus chick embryo cells was compared with that of aged cells. In contrast to the nuclei of young chick embryo cells 24 hr after infection, the aged chick embryo cells 24 hr after infection presented very expressive blocks of perinuclear chromatin. The nucleoplasm contains forming naked HSV particles. The lesions seen are dilation of the perinuclear cisternae, dilatation of rough endoplasmic reticulum cisternae and formation of multilamellar bodies. The moderate swellings of the mitochondria with violation of cristae arrangement and losing of mitochondrial matrix were observed. In contrast to the cytoplasm of young infected cells no formation of crystal-like arrangement of cytoplasmic ribosome tetrads occurs.", "contents": "Ultrastructure of in vitro aged chick embryo cell cultures in relation to viral infection. The ultrastructure of young uninfected and infected with herpes simplex virus chick embryo cells was compared with that of aged cells. In contrast to the nuclei of young chick embryo cells 24 hr after infection, the aged chick embryo cells 24 hr after infection presented very expressive blocks of perinuclear chromatin. The nucleoplasm contains forming naked HSV particles. The lesions seen are dilation of the perinuclear cisternae, dilatation of rough endoplasmic reticulum cisternae and formation of multilamellar bodies. The moderate swellings of the mitochondria with violation of cristae arrangement and losing of mitochondrial matrix were observed. In contrast to the cytoplasm of young infected cells no formation of crystal-like arrangement of cytoplasmic ribosome tetrads occurs."} {"id": "PMID:164110", "title": "Pathogenetic mechanisms in atherosclerosis.", "content": "Four theories of atherogenesis are briefly reviewed and criticized: the degenerative, the thrombogenic, the platelet aggregation and the insudative theory. Evidence is presented in detail to suggest that a modified form of the insudative theory (1) accounts more satisfactorily than the other theories for the known association of risk factors with atherosclerosis and (2) allows one to understand how some of the more important risk factors operate at the level of the arterial wall. It is proposed that atherosclerotic plaques, and also certain extravascular lesions broadly associated with atherosclerosis (corneal arcus, xanthomas), arise because altered endothelial permeability allows certain reactive macromolecular plasma proteins (the plasma low density and very low density lipoproteins and fibrinogen, which are normally largely confined to the circulation) to permeate endothelium and interact with charged components of the connective tissue gel of the arterial wall or other tissues. The effect of hyperlipidemia, hypertension, arterial disease or injury upon this process, and the manner in which these factors interact, is examined in relation to experimental findings and clinical observations.", "contents": "Pathogenetic mechanisms in atherosclerosis. Four theories of atherogenesis are briefly reviewed and criticized: the degenerative, the thrombogenic, the platelet aggregation and the insudative theory. Evidence is presented in detail to suggest that a modified form of the insudative theory (1) accounts more satisfactorily than the other theories for the known association of risk factors with atherosclerosis and (2) allows one to understand how some of the more important risk factors operate at the level of the arterial wall. It is proposed that atherosclerotic plaques, and also certain extravascular lesions broadly associated with atherosclerosis (corneal arcus, xanthomas), arise because altered endothelial permeability allows certain reactive macromolecular plasma proteins (the plasma low density and very low density lipoproteins and fibrinogen, which are normally largely confined to the circulation) to permeate endothelium and interact with charged components of the connective tissue gel of the arterial wall or other tissues. The effect of hyperlipidemia, hypertension, arterial disease or injury upon this process, and the manner in which these factors interact, is examined in relation to experimental findings and clinical observations."} {"id": "PMID:164111", "title": "Mechanisms of cholesterol accumulation in the arterial wall.", "content": "The rate of cholesterol accumulation is a function of three separate processes: the transfer of lipid or lipoprotein from blood plasma to the artery, the binding and sequestering of lipids in the arterial wall and the solubilization and removal of lipid from the artery. These processes have been studied with lipids or lipoproteins labeled with radioisotopes by autoradiographic and quantitative chemical procedures. More recently immunochemical procedures have been applied to this problem. Studies have been performed with intact animals, isolated organs and cell cultures. In addition, homogenates have been used successfully to study intraarterial transformations of lipids, (for example, cholesterol esterification). Although epidemiologic and clinical studies, as well as animal experiments, have provided evidence that the concentration of plasma low or very low density lipoproteins parallels the rate of atherogenesis, the nature of the causal chain linking plasma lipoproteins to atherosclerosis is as yet unclear. A possible link between plasma lipoproteins, arterial liproprotein lipase and atherogenesis has been postulated.", "contents": "Mechanisms of cholesterol accumulation in the arterial wall. The rate of cholesterol accumulation is a function of three separate processes: the transfer of lipid or lipoprotein from blood plasma to the artery, the binding and sequestering of lipids in the arterial wall and the solubilization and removal of lipid from the artery. These processes have been studied with lipids or lipoproteins labeled with radioisotopes by autoradiographic and quantitative chemical procedures. More recently immunochemical procedures have been applied to this problem. Studies have been performed with intact animals, isolated organs and cell cultures. In addition, homogenates have been used successfully to study intraarterial transformations of lipids, (for example, cholesterol esterification). Although epidemiologic and clinical studies, as well as animal experiments, have provided evidence that the concentration of plasma low or very low density lipoproteins parallels the rate of atherogenesis, the nature of the causal chain linking plasma lipoproteins to atherosclerosis is as yet unclear. A possible link between plasma lipoproteins, arterial liproprotein lipase and atherogenesis has been postulated."} {"id": "PMID:164112", "title": "Aortic mitochondrial synthesis of lipid and its response to cholesterol feeding.", "content": "The rates and products of lipid synthesis from acetate-I-14C were studied in mitochondria isolated from control and atherosclerotic rabbit aorta. More acetate was incorporated into fatty acids in the cholesterol-fed animals. The mechanism was one of chain elongation, and the resultant products were longer in chain length. The newly elongated fatty acids were esterified mostly into phospholipids, presumably those turning over most rapidly. A hypothesis is proposed for the pathogenetic sequence: Cholesterol feeding alters transport functions of the mitochondrial membranes of aortic smooth muscle cells. Respiration and redox state are altered and consequently acetate is incorporated more rapidly into fatty acids as an alternate mechanism for oxidation of the reduced form of nicotin-amide-adenine dinucleotide (NADH). Rapidly turning over phospholipids esterify these fatty acids and may transfer them ultimately to cholesterol. Esterified cholesterol is less exchangeable and commences to accumulate.", "contents": "Aortic mitochondrial synthesis of lipid and its response to cholesterol feeding. The rates and products of lipid synthesis from acetate-I-14C were studied in mitochondria isolated from control and atherosclerotic rabbit aorta. More acetate was incorporated into fatty acids in the cholesterol-fed animals. The mechanism was one of chain elongation, and the resultant products were longer in chain length. The newly elongated fatty acids were esterified mostly into phospholipids, presumably those turning over most rapidly. A hypothesis is proposed for the pathogenetic sequence: Cholesterol feeding alters transport functions of the mitochondrial membranes of aortic smooth muscle cells. Respiration and redox state are altered and consequently acetate is incorporated more rapidly into fatty acids as an alternate mechanism for oxidation of the reduced form of nicotin-amide-adenine dinucleotide (NADH). Rapidly turning over phospholipids esterify these fatty acids and may transfer them ultimately to cholesterol. Esterified cholesterol is less exchangeable and commences to accumulate."} {"id": "PMID:164113", "title": "Lipid metabolism in perfused human and dog coronary arteries.", "content": "The paper represents a summary of our studies in which in vitro perfusion of human and animal coronary vessels was carried out. Formation and uptake of lipids in perfused human coronary arteries were studied under a vairety of experimental conditions, including exposure to carbon monoxide. The effect of collagenase on lipid synthesis and transport in carotid arteries of dogs was also studied. Human plasma with hydrogen-3-labeled cholesterol and carbon-14-acetate was used to perfuse human blood vessels. Autologous plasma was employed. Inhibition of cholesterol uptake was accomplished by the addition of 7-ketocholesterol (concentrations of 0.005 to 1 mum/ml) to the perfusate. Both atherosclerotic and normal human coronary arteries incorporated 14C-acetate into lipids but failed to synthesize either cholesterol of cholesterol esters. Similar results were obtained in human saphenous veins perfused at arterial pressure. Cholesterol uptake from the perfusion fluid was demonstrated in atherosclerotic and normal human coronary arteries as well as in human saphenous veins. Carbon monoxide increased permeability of the arterial wall to cholesterol uptake. In dog arteries exposed to collagenase marked increases in cholesterol uptake were found, but total lipid synthesis was reduced; the relative synthesis individual lipids remained unchanged. The addition of 7-ketocholesterol to the perfusate reduced cholesterol uptake by the vessel by 90 percent. Inhibition of cholesterol uptake was present in all species and was not due to oxidation of cholesterol to 7-detocholesterol in the perfusate. The results illustrate that human coronary arteries as well as human saphenous veins synthesize lipids but not cholesterol. Cholesterol flux into the artery is augmented by carbon monoxide and collagenase. The data also show that active inhibition of cholesterol uptake in the arterial wall can be accomplished by competitive inhibition with 7-ketocholesterol.", "contents": "Lipid metabolism in perfused human and dog coronary arteries. The paper represents a summary of our studies in which in vitro perfusion of human and animal coronary vessels was carried out. Formation and uptake of lipids in perfused human coronary arteries were studied under a vairety of experimental conditions, including exposure to carbon monoxide. The effect of collagenase on lipid synthesis and transport in carotid arteries of dogs was also studied. Human plasma with hydrogen-3-labeled cholesterol and carbon-14-acetate was used to perfuse human blood vessels. Autologous plasma was employed. Inhibition of cholesterol uptake was accomplished by the addition of 7-ketocholesterol (concentrations of 0.005 to 1 mum/ml) to the perfusate. Both atherosclerotic and normal human coronary arteries incorporated 14C-acetate into lipids but failed to synthesize either cholesterol of cholesterol esters. Similar results were obtained in human saphenous veins perfused at arterial pressure. Cholesterol uptake from the perfusion fluid was demonstrated in atherosclerotic and normal human coronary arteries as well as in human saphenous veins. Carbon monoxide increased permeability of the arterial wall to cholesterol uptake. In dog arteries exposed to collagenase marked increases in cholesterol uptake were found, but total lipid synthesis was reduced; the relative synthesis individual lipids remained unchanged. The addition of 7-ketocholesterol to the perfusate reduced cholesterol uptake by the vessel by 90 percent. Inhibition of cholesterol uptake was present in all species and was not due to oxidation of cholesterol to 7-detocholesterol in the perfusate. The results illustrate that human coronary arteries as well as human saphenous veins synthesize lipids but not cholesterol. Cholesterol flux into the artery is augmented by carbon monoxide and collagenase. The data also show that active inhibition of cholesterol uptake in the arterial wall can be accomplished by competitive inhibition with 7-ketocholesterol."} {"id": "PMID:164114", "title": "Function of the fat-soluble vitamins.", "content": "Much has been learned about the function of the fat-soluble vitamins in recent years. Their mechanisms are divergent ranging from a role in transcription of DNA or differentiation to a direct enzymatic activation of the gamma-carboxylation of glutamate residues of a preexisting protein. Thus the only resemblance so far among these physiologically active agents is their lipid solubility. However, in general the fat-soluble vitamins play important roles in specialized functions carried out by highly differentiated organisms.", "contents": "Function of the fat-soluble vitamins. Much has been learned about the function of the fat-soluble vitamins in recent years. Their mechanisms are divergent ranging from a role in transcription of DNA or differentiation to a direct enzymatic activation of the gamma-carboxylation of glutamate residues of a preexisting protein. Thus the only resemblance so far among these physiologically active agents is their lipid solubility. However, in general the fat-soluble vitamins play important roles in specialized functions carried out by highly differentiated organisms."} {"id": "PMID:164115", "title": "On certain electrical phenomena for the interpretation of ch'i in Chinese acupuncture.", "content": "The author describes a series of experiments on the \"microelectric phenomenon\" and tires to give new scientific interpretations of acupuncture. Thus, the concept of \"2-M-C\" was developed, which may generate new hypotheses concerning the modus operandi of needle treatment.", "contents": "On certain electrical phenomena for the interpretation of ch'i in Chinese acupuncture. The author describes a series of experiments on the \"microelectric phenomenon\" and tires to give new scientific interpretations of acupuncture. Thus, the concept of \"2-M-C\" was developed, which may generate new hypotheses concerning the modus operandi of needle treatment."} {"id": "PMID:164116", "title": "Limits of applicability of the firefly luminescence ATP assay for the detection of bacteria in clinical specimens.", "content": "ATP measurement can be used as an indicator of biological mass, and the extreme sensitivity of the firefly ATP assay has led to its use in bacterial detection systems. Clinical specimens present problems not encountered with cultured isolates of known bacterial species. The lower limit of sensitivity for detecting bacteria using the firefly assay is 100,000 bacteria per ml. Non-bacterial ATP, which is probably present in all clinical specimens, produces false-positive results unless it is completely destroyed, and this destruction must be carried out under conditions that do not affect bacterial ATP. A cause of false-negative results is the presence in all urine specimens of unidentified materials that inhibit the luminescent enzymic reaction. These considerations indicate that application of the firefly ATP assay in bacterial detection systems for clinical specimens is feasible only if a preparatory step separates bacteria from interfering materials and from non-bacterial sources of ATP, and concentrates microorganisms to measurable levels. These limitations sharply curtain the applicability in diagnostic microbiology of this exotic chemical reaction.", "contents": "Limits of applicability of the firefly luminescence ATP assay for the detection of bacteria in clinical specimens. ATP measurement can be used as an indicator of biological mass, and the extreme sensitivity of the firefly ATP assay has led to its use in bacterial detection systems. Clinical specimens present problems not encountered with cultured isolates of known bacterial species. The lower limit of sensitivity for detecting bacteria using the firefly assay is 100,000 bacteria per ml. Non-bacterial ATP, which is probably present in all clinical specimens, produces false-positive results unless it is completely destroyed, and this destruction must be carried out under conditions that do not affect bacterial ATP. A cause of false-negative results is the presence in all urine specimens of unidentified materials that inhibit the luminescent enzymic reaction. These considerations indicate that application of the firefly ATP assay in bacterial detection systems for clinical specimens is feasible only if a preparatory step separates bacteria from interfering materials and from non-bacterial sources of ATP, and concentrates microorganisms to measurable levels. These limitations sharply curtain the applicability in diagnostic microbiology of this exotic chemical reaction."} {"id": "PMID:164119", "title": "Granular cell tumor (myoblastoma) of the orbit.", "content": "An 8-year-old white boy had a tumor in the left orbit with clinical manifestations of muscular impairment, exophthalmos, and reduced visual acuity. Five months after exenteration of the orbit the boy was healthy without tumor recurrence. Based on our observations with electron, light, and phase microscopy, and histochemical studies, we conclude that this tumor is benign, of histiocytic origin, and we propose the term granular cell histiocytoma be used to describe this entity.", "contents": "Granular cell tumor (myoblastoma) of the orbit. An 8-year-old white boy had a tumor in the left orbit with clinical manifestations of muscular impairment, exophthalmos, and reduced visual acuity. Five months after exenteration of the orbit the boy was healthy without tumor recurrence. Based on our observations with electron, light, and phase microscopy, and histochemical studies, we conclude that this tumor is benign, of histiocytic origin, and we propose the term granular cell histiocytoma be used to describe this entity."} {"id": "PMID:164120", "title": "Occupational therapy in a community aftercare program.", "content": "The need for effective community treatment for psychiatric clients has increased in recent years. The aftercare program descirbed in this paper provides a community treatment program for adult psychiatric clients that aims at facilitatin their adequate and independent adjustment to the community. The occupational therapist functions as a case manager of the treaatment team and is also program coordinator for the arts and crafts groups and the skill development groups. The arts and crafts groups are designed primarily to meet basic mental health needs; the skill development groups are aimed at teaching independent functioning in basic living skills. The behavior rehearsal model provides the theoretical framework for the skill development groups and is an effective approach in teaching skill acquisition to clients treated in the community.", "contents": "Occupational therapy in a community aftercare program. The need for effective community treatment for psychiatric clients has increased in recent years. The aftercare program descirbed in this paper provides a community treatment program for adult psychiatric clients that aims at facilitatin their adequate and independent adjustment to the community. The occupational therapist functions as a case manager of the treaatment team and is also program coordinator for the arts and crafts groups and the skill development groups. The arts and crafts groups are designed primarily to meet basic mental health needs; the skill development groups are aimed at teaching independent functioning in basic living skills. The behavior rehearsal model provides the theoretical framework for the skill development groups and is an effective approach in teaching skill acquisition to clients treated in the community."} {"id": "PMID:164121", "title": "Ultrastructure of medullary, intraductal, tubular and adenocystic breast carcinomas: comparative patterns of myoepithelial differentiation and basal lamina deposition.", "content": "Samples from medullary, intraductal, tubular and adenocystic breast carcinomas were studied ultrastructurally, with emphasis on the patterns of myoepithelial differentiation and basal lamina deposition. Myoepithelial cells, while prominent in the intraductal and adenocystic carcinomas, were rarely found in the medullary neoplasms and appeared absent in the tubular neoplasms. Parallel to the above, basal laminae were most abundant and evenly deposited in the intraductal and adenocystic tumors, but were infrequent in the medullary tumors and seemingly absent in the tubular carcinomas. Well-defined myoepithelial cells and retention of the capability to synthesize basal lamina are evidence of differentiation in neoplastic cell populations. Thus, their presence in intraductal and adenocystic carcinomas (generally associated with a good prognosis) is not surprising. However, their scarcity or absence in the similarly favorable group of medullary and tubular carcinomas suggests that other factors may also influence the invasive and metastasizing ability of breast carcinomas.", "contents": "Ultrastructure of medullary, intraductal, tubular and adenocystic breast carcinomas: comparative patterns of myoepithelial differentiation and basal lamina deposition. Samples from medullary, intraductal, tubular and adenocystic breast carcinomas were studied ultrastructurally, with emphasis on the patterns of myoepithelial differentiation and basal lamina deposition. Myoepithelial cells, while prominent in the intraductal and adenocystic carcinomas, were rarely found in the medullary neoplasms and appeared absent in the tubular neoplasms. Parallel to the above, basal laminae were most abundant and evenly deposited in the intraductal and adenocystic tumors, but were infrequent in the medullary tumors and seemingly absent in the tubular carcinomas. Well-defined myoepithelial cells and retention of the capability to synthesize basal lamina are evidence of differentiation in neoplastic cell populations. Thus, their presence in intraductal and adenocystic carcinomas (generally associated with a good prognosis) is not surprising. However, their scarcity or absence in the similarly favorable group of medullary and tubular carcinomas suggests that other factors may also influence the invasive and metastasizing ability of breast carcinomas."} {"id": "PMID:164122", "title": "The nuclear membranes in hypertrophied human cardiac muscle cells.", "content": "Nuclear membranes of cardiac muscle cells were studied in 134 patients with cardiac hypertrophy of various causes. Abnormalities observed consisted of: a) increased foldings and convolutions; b) nuclear pseudoinclusions formed by cytoplasmic organelles protruding into saccular invaginations of the nuclear membranes, and c) intranuclear tubules. The increased foldings and convolutions of the nuclear membranes and the nuclear pseudoinclusions appear to result from synthesis of nuclear membranes in excess of that needed to accommodate the increase in nuclear volume which occurs in hypertrophy. Intranuclear tubules were found in 6 patients and consisted of tubular invaginations, 400 to 650 A in diameter, of the inner nuclear membranes into the nucleoplasm. Some of these tubules were straight and cylindrical, and were associated with a peripheral layer of marginated chromatin; others were not associated with chromatin, appeared coiled and followed irregular courses. Intranuclear tubules in cardiac muscle cells probably represent an extreme cellular response to the stimulus of hypertrophy.", "contents": "The nuclear membranes in hypertrophied human cardiac muscle cells. Nuclear membranes of cardiac muscle cells were studied in 134 patients with cardiac hypertrophy of various causes. Abnormalities observed consisted of: a) increased foldings and convolutions; b) nuclear pseudoinclusions formed by cytoplasmic organelles protruding into saccular invaginations of the nuclear membranes, and c) intranuclear tubules. The increased foldings and convolutions of the nuclear membranes and the nuclear pseudoinclusions appear to result from synthesis of nuclear membranes in excess of that needed to accommodate the increase in nuclear volume which occurs in hypertrophy. Intranuclear tubules were found in 6 patients and consisted of tubular invaginations, 400 to 650 A in diameter, of the inner nuclear membranes into the nucleoplasm. Some of these tubules were straight and cylindrical, and were associated with a peripheral layer of marginated chromatin; others were not associated with chromatin, appeared coiled and followed irregular courses. Intranuclear tubules in cardiac muscle cells probably represent an extreme cellular response to the stimulus of hypertrophy."} {"id": "PMID:164123", "title": "Ultrastructure of inclusions in peripheral blood mononuclear cells in sarcoidosis.", "content": "Bundle-shaped tubular (BST) inclusions were identified by electron microscopy in 1 to 6 percent of peripheral blood mononuclear cells obtained from 10 to 11 patients with sarcoidosis. The frequency of the inclusions within mononuclear cells did not correlate with the clinical status of the patients. The relationship, if any, of BST inclusions to sarcoidosis and the immunologic defects in sarcoid patients remains to be determined.", "contents": "Ultrastructure of inclusions in peripheral blood mononuclear cells in sarcoidosis. Bundle-shaped tubular (BST) inclusions were identified by electron microscopy in 1 to 6 percent of peripheral blood mononuclear cells obtained from 10 to 11 patients with sarcoidosis. The frequency of the inclusions within mononuclear cells did not correlate with the clinical status of the patients. The relationship, if any, of BST inclusions to sarcoidosis and the immunologic defects in sarcoid patients remains to be determined."} {"id": "PMID:164126", "title": "Effect of ACTH on lipolysis in adipose tissue of normal and adrenalectomized rats in vivo.", "content": "Parametrial fat-pads of fed rats were perfused in vivo. Rates of release of glycerol and free fatty acids (FFA) were determined from venous-arterial difference and plasma flow. Adrenalectomy lowered basal release of FFA and glycerol, but not reesterification of FFA within the fat-pad. ACTH (5 mug iv) in normal rats increased release of FFA and glycerol (mumol-g-1-h-1) from basal values of 0.90 and 0.48 to 3.2 and 1.3, respectively, and in adrenalectomized rats from 0.41 and 0.33 to 1.5 and 3.1, respectively. Thus in normal rats ACTH increased the molar ratio of FFA to glycerol released from 1.9 to 2.5, whereas in adrenalectomized rats the ratio fell from 1.3 to 0.5. After stimulation of lipolysis in normal rats 85% of the FFA formed were released but only 20% in adrenalectomized rats; the remainder was reesterified to triglyceride. It is concluded that adipose tissue of adrenalectomized rats is sensitive to the lipolytic activity of ACTH, but increased glucose utilization by adipocytes in the absence of glucocorticoid enhances reesterification and reduces release of FFA by the tissue.", "contents": "Effect of ACTH on lipolysis in adipose tissue of normal and adrenalectomized rats in vivo. Parametrial fat-pads of fed rats were perfused in vivo. Rates of release of glycerol and free fatty acids (FFA) were determined from venous-arterial difference and plasma flow. Adrenalectomy lowered basal release of FFA and glycerol, but not reesterification of FFA within the fat-pad. ACTH (5 mug iv) in normal rats increased release of FFA and glycerol (mumol-g-1-h-1) from basal values of 0.90 and 0.48 to 3.2 and 1.3, respectively, and in adrenalectomized rats from 0.41 and 0.33 to 1.5 and 3.1, respectively. Thus in normal rats ACTH increased the molar ratio of FFA to glycerol released from 1.9 to 2.5, whereas in adrenalectomized rats the ratio fell from 1.3 to 0.5. After stimulation of lipolysis in normal rats 85% of the FFA formed were released but only 20% in adrenalectomized rats; the remainder was reesterified to triglyceride. It is concluded that adipose tissue of adrenalectomized rats is sensitive to the lipolytic activity of ACTH, but increased glucose utilization by adipocytes in the absence of glucocorticoid enhances reesterification and reduces release of FFA by the tissue."} {"id": "PMID:164127", "title": "Postnatal development of adenylate cyclase in rat salivary glands: patterns of hormonal sensitivity.", "content": "In order to compare the known morphological changes which occur during the postnatal development of the salivary glands in the rat with alterations in membrane function, we measured adenylate cyclase activity and its responses to sodium fluoride (NaF), norepinephrine, and isoproterenol in salivary gland membranes at various times after birth. In the parotid gland, basal enzyme activity did not change significantly during postnatal life, but fluoride-stimulated activity rose on day 15; A similar marked rise in activity stimulated by norepinephrine (0.02 mM) and isoproterenol (0.03 mM) was noted simultaneously. In the submandibular gland, basal adenylate cyclase activity was higher just after birth than at 25 days of life or in maturity. Fluoride-stimulated activity was 7 times higher than basal activity on day 1, greater than 10 times higher on day 25, and 30 times greater in the adult. The gland was as responsive to norepinephrine and isoproterenol on day 5 as it was on day 25 or in the mature animal, showing a two- to threefold increase over the basal enzyme value at each time point studied. Residual phosphodiesterase activity in the membranes was always negligible. The data demonstrate a time-dependent developmental change in the responsiveness of the parotid gland to norepinephrine and isoproterenol, which corresponds to the time when morphological maturation normally occurs. By contrast, in the submandibular gland, membrane-bound adenylate cyclase is fully developed at the time of birth.", "contents": "Postnatal development of adenylate cyclase in rat salivary glands: patterns of hormonal sensitivity. In order to compare the known morphological changes which occur during the postnatal development of the salivary glands in the rat with alterations in membrane function, we measured adenylate cyclase activity and its responses to sodium fluoride (NaF), norepinephrine, and isoproterenol in salivary gland membranes at various times after birth. In the parotid gland, basal enzyme activity did not change significantly during postnatal life, but fluoride-stimulated activity rose on day 15; A similar marked rise in activity stimulated by norepinephrine (0.02 mM) and isoproterenol (0.03 mM) was noted simultaneously. In the submandibular gland, basal adenylate cyclase activity was higher just after birth than at 25 days of life or in maturity. Fluoride-stimulated activity was 7 times higher than basal activity on day 1, greater than 10 times higher on day 25, and 30 times greater in the adult. The gland was as responsive to norepinephrine and isoproterenol on day 5 as it was on day 25 or in the mature animal, showing a two- to threefold increase over the basal enzyme value at each time point studied. Residual phosphodiesterase activity in the membranes was always negligible. The data demonstrate a time-dependent developmental change in the responsiveness of the parotid gland to norepinephrine and isoproterenol, which corresponds to the time when morphological maturation normally occurs. By contrast, in the submandibular gland, membrane-bound adenylate cyclase is fully developed at the time of birth."} {"id": "PMID:164128", "title": "Brief hospitalization of patients with families: initial results.", "content": "A total of 175 newly admitted inpatients who lived with families were randomly assigned to three treatment groups: standard inpatient care (discharge at the therapist's discretion), brief hospitalization (one week or less) with transitional day care available, and brief hospitalization without day care. Outpatient aftercare was offered to all patients. The three groups showed no significant differences as to amount of improvement in levels of psychopathology at 3 and 12 weeks, but the briefly hospitalized patients were able to resume their vocational roles sooner. There were no significant differences among the groups in readmission rates.", "contents": "Brief hospitalization of patients with families: initial results. A total of 175 newly admitted inpatients who lived with families were randomly assigned to three treatment groups: standard inpatient care (discharge at the therapist's discretion), brief hospitalization (one week or less) with transitional day care available, and brief hospitalization without day care. Outpatient aftercare was offered to all patients. The three groups showed no significant differences as to amount of improvement in levels of psychopathology at 3 and 12 weeks, but the briefly hospitalized patients were able to resume their vocational roles sooner. There were no significant differences among the groups in readmission rates."} {"id": "PMID:164129", "title": "Alternative to the hospital: a controlled study.", "content": "The authors describe the evaluation of a treatment model that makes use of the community to help mentally ill patients acquire necessary coping skills. This approach is based on the assumption that deficiency in coping skills and aggressive dependency are primarily responsible for high readmission rates to mental hospitals and that coping skills and autonomy are best learned in the community, where the patient will be needing and using them. The treatment model is evaluated by comparing it with progressive in-hospital treatment and follow-up care. The results suggest that the model described can successfully treat patients with a high level of symptomatology in the community rather than in the mental hospital.", "contents": "Alternative to the hospital: a controlled study. The authors describe the evaluation of a treatment model that makes use of the community to help mentally ill patients acquire necessary coping skills. This approach is based on the assumption that deficiency in coping skills and aggressive dependency are primarily responsible for high readmission rates to mental hospitals and that coping skills and autonomy are best learned in the community, where the patient will be needing and using them. The treatment model is evaluated by comparing it with progressive in-hospital treatment and follow-up care. The results suggest that the model described can successfully treat patients with a high level of symptomatology in the community rather than in the mental hospital."} {"id": "PMID:164130", "title": "Arteriographic demonstration of intravenous tumor extension.", "content": "The arteriographic demonstration of a linear, striated arterial pattern in the anatomic course of the draining vein is reliable evidence of venous extension by a tumor and represents the supply to the intravenous component of the neoplasm. In addition to its previously described occurrence with hypernephromas, this report documents the characteristic angiographic appearance with hepatocellular tumors and a retroperitoneal osteosarcoma as reliable evidence of tumor extension into the inferior vena cava. It is possible that in some cases, the parallel arteries represent markedly enlarged vasa vasorum of the involved venous structure. The frequent invasion of the inferior vena cava by hepatomas and the importance of inferior vena cavography in their angiographic evaluation is also emphasized.", "contents": "Arteriographic demonstration of intravenous tumor extension. The arteriographic demonstration of a linear, striated arterial pattern in the anatomic course of the draining vein is reliable evidence of venous extension by a tumor and represents the supply to the intravenous component of the neoplasm. In addition to its previously described occurrence with hypernephromas, this report documents the characteristic angiographic appearance with hepatocellular tumors and a retroperitoneal osteosarcoma as reliable evidence of tumor extension into the inferior vena cava. It is possible that in some cases, the parallel arteries represent markedly enlarged vasa vasorum of the involved venous structure. The frequent invasion of the inferior vena cava by hepatomas and the importance of inferior vena cavography in their angiographic evaluation is also emphasized."} {"id": "PMID:164131", "title": "Metastatic disease of the sella turcica.", "content": "Eleven cases of known metastatic disease to the sella turcica are reported. The clinical, plain film roentgenographic and angiographic presentations are discussed with reference to the differential diagnosis and possible distinguishing characteristics of metastatic disease.", "contents": "Metastatic disease of the sella turcica. Eleven cases of known metastatic disease to the sella turcica are reported. The clinical, plain film roentgenographic and angiographic presentations are discussed with reference to the differential diagnosis and possible distinguishing characteristics of metastatic disease."} {"id": "PMID:164132", "title": "Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy.", "content": "A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an adequate procedure for low-grade, nonaggressive lesions. The addition of radiation therapy postoperatively will improve local and regional control of high-grade, aggressive lesions. Postoperative radiation therapy may also make the removal of the facial nerve unnecessary in certain clinical presentations.", "contents": "Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an adequate procedure for low-grade, nonaggressive lesions. The addition of radiation therapy postoperatively will improve local and regional control of high-grade, aggressive lesions. Postoperative radiation therapy may also make the removal of the facial nerve unnecessary in certain clinical presentations."} {"id": "PMID:164133", "title": "Metastatic seeding along the small bowel mesentery. Roentgen features.", "content": "1. Intra-abdominal malignant seeding along the small bowel mesentery is roentgenologically identifiable. 2. The anatomic features of the small bowel mesentery and the pathways of flow of ascitic fluid along its peritoneal recesses determine the depostion and growth of seeded metastases. 3. Seeded deposits lodge particularly within the lower recesses of the small bowel mesentery and are reflected by typical changes involving distal ileal loops or the cecum. 4. These are characterized by (a) palisading, arcuate scalloped deflections or gross mass displacement of distal small bowel loops in the right lower quadrant, or (b) extrinsic indentations upon the medial and inferior contours of the cecum. Associated desmoplastic reaction may result in tethering of mucosal folds and angulated fixation of bowel loops.", "contents": "Metastatic seeding along the small bowel mesentery. Roentgen features. 1. Intra-abdominal malignant seeding along the small bowel mesentery is roentgenologically identifiable. 2. The anatomic features of the small bowel mesentery and the pathways of flow of ascitic fluid along its peritoneal recesses determine the depostion and growth of seeded metastases. 3. Seeded deposits lodge particularly within the lower recesses of the small bowel mesentery and are reflected by typical changes involving distal ileal loops or the cecum. 4. These are characterized by (a) palisading, arcuate scalloped deflections or gross mass displacement of distal small bowel loops in the right lower quadrant, or (b) extrinsic indentations upon the medial and inferior contours of the cecum. Associated desmoplastic reaction may result in tethering of mucosal folds and angulated fixation of bowel loops."} {"id": "PMID:164134", "title": "Ecology of respiratory virus transmission: a comparison of three communities in West Bengal.", "content": "Respiratory virus transmission in children was studied comparatively in three ecologically different low-income communities in West Bengal: an isolated village, a suburban village, and a crowded urban community. Continued use of contaminated pond water for bathing, irrigation of nasal passages, post-defecation washing of the anus, and washing of food vessels was common to all, as was intense crowding of indoor sleeping quarters during cold and wet seasons. Intensity of infection was highest (26%) in the most crowded urban area, the variety of virus types least in the most isolated village. Sources of drinking water differed but seemed unrelated to virus transmission. Toxigenic diphtheria organisms were found in nonspecific skin lesions in children in each area.", "contents": "Ecology of respiratory virus transmission: a comparison of three communities in West Bengal. Respiratory virus transmission in children was studied comparatively in three ecologically different low-income communities in West Bengal: an isolated village, a suburban village, and a crowded urban community. Continued use of contaminated pond water for bathing, irrigation of nasal passages, post-defecation washing of the anus, and washing of food vessels was common to all, as was intense crowding of indoor sleeping quarters during cold and wet seasons. Intensity of infection was highest (26%) in the most crowded urban area, the variety of virus types least in the most isolated village. Sources of drinking water differed but seemed unrelated to virus transmission. Toxigenic diphtheria organisms were found in nonspecific skin lesions in children in each area."} {"id": "PMID:164135", "title": "Crimean hemorrhagic fever-Congo (CHF-C) virus antibodies in man, and in domestic and small mammals, in Iran.", "content": "A Crimean hemorrhagic fever-Congo (CHF-C) virus antibody survey was carried out in Iran with sera from man and several animal species; this survey was done by means of agar gel diffusion precipitation (AGDP) test with the following results (percent positive of number tested): men, 13% of 351; sheep, 38% of 728; goats, 36% of 135; cattle, 18% of 130; camels, 0% of 157; small mammals, 3% of 274. A number of sera were tested by complement-fixation (CF), neutralization (N), and hemagglutination-inhibition (HI) tests in addition to the AGDP test. A good correlation was found in the results with 105 sera tested by AGDP, HI, and N, with approximately 70% to 75% positive in all three tests; by CF, only 20% were positive. Of 55 human sera, of which 15 could be tested by N test, about half were positive by AGDP and only 10% by HI at low titers; none was positive by N and CF tests. These results suggest that any one of the three serological tests (N, HI, and AGDP) can be used to survey the antibody prevalence in sera from domestic animals; the CF test, not unexpectedly, was less suitable. Our results, however, are inconclusive in regard to the human sera.", "contents": "Crimean hemorrhagic fever-Congo (CHF-C) virus antibodies in man, and in domestic and small mammals, in Iran. A Crimean hemorrhagic fever-Congo (CHF-C) virus antibody survey was carried out in Iran with sera from man and several animal species; this survey was done by means of agar gel diffusion precipitation (AGDP) test with the following results (percent positive of number tested): men, 13% of 351; sheep, 38% of 728; goats, 36% of 135; cattle, 18% of 130; camels, 0% of 157; small mammals, 3% of 274. A number of sera were tested by complement-fixation (CF), neutralization (N), and hemagglutination-inhibition (HI) tests in addition to the AGDP test. A good correlation was found in the results with 105 sera tested by AGDP, HI, and N, with approximately 70% to 75% positive in all three tests; by CF, only 20% were positive. Of 55 human sera, of which 15 could be tested by N test, about half were positive by AGDP and only 10% by HI at low titers; none was positive by N and CF tests. These results suggest that any one of the three serological tests (N, HI, and AGDP) can be used to survey the antibody prevalence in sera from domestic animals; the CF test, not unexpectedly, was less suitable. Our results, however, are inconclusive in regard to the human sera."} {"id": "PMID:164136", "title": "Islet cell tumors of the pancreas and the alimentary tract.", "content": "Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely.", "contents": "Islet cell tumors of the pancreas and the alimentary tract. Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely."} {"id": "PMID:164137", "title": "Immunochemotherapy of hepatoma in rats.", "content": "Immunoglobulin G prepared by immunization of rabbits with rat Novikoff ascites tumor cells was prepared and found to by cytotoxic to Novikoff cells and rat lymphocytes. A chlorambucil conjugate was prepared and found to have similar qualities in vitro. Three day culture systems were prepared with various test substances and the immunoglobulin was shown to markedly depress cell multiplication. The chlorambucil conjugate appeared to be more efficacious than the immunoglobulin alone in inhibiting cell growth. In vivo studies revealed a total inhibition of tumor formation in animals treated with the immunoglobulin-chlorambucil conjugate whereas all control groups had 50 to 100 per cent mortality. No systemic toxicity was apparent. These studies indicate that tumor-specific immunoglobulin bound to chlorambucil presents a feasible method of delivering tumoricidal drugs to cancer in body cavities and of treating tumors with an accessible blood supply.", "contents": "Immunochemotherapy of hepatoma in rats. Immunoglobulin G prepared by immunization of rabbits with rat Novikoff ascites tumor cells was prepared and found to by cytotoxic to Novikoff cells and rat lymphocytes. A chlorambucil conjugate was prepared and found to have similar qualities in vitro. Three day culture systems were prepared with various test substances and the immunoglobulin was shown to markedly depress cell multiplication. The chlorambucil conjugate appeared to be more efficacious than the immunoglobulin alone in inhibiting cell growth. In vivo studies revealed a total inhibition of tumor formation in animals treated with the immunoglobulin-chlorambucil conjugate whereas all control groups had 50 to 100 per cent mortality. No systemic toxicity was apparent. These studies indicate that tumor-specific immunoglobulin bound to chlorambucil presents a feasible method of delivering tumoricidal drugs to cancer in body cavities and of treating tumors with an accessible blood supply."} {"id": "PMID:164138", "title": "[Clinical considerations and genetics of the lattice dystrophy of the cornea].", "content": "Lattice dystrophy of the cornea is reported in 4 families. For purposes of linkage analysis we did serological tests on pertinent family members, including marker testing of the blood group systems ABO, MNSs, Rh, K, Ky, and P; protein group systems Hp, Ge, Gm, and Inv; and enzyme polymorphisms SEP, PGM, ADA, and AK.", "contents": "[Clinical considerations and genetics of the lattice dystrophy of the cornea]. Lattice dystrophy of the cornea is reported in 4 families. For purposes of linkage analysis we did serological tests on pertinent family members, including marker testing of the blood group systems ABO, MNSs, Rh, K, Ky, and P; protein group systems Hp, Ge, Gm, and Inv; and enzyme polymorphisms SEP, PGM, ADA, and AK."} {"id": "PMID:164139", "title": "Permeability barriers to cytochrome-c in nerves of adult and immature rats.", "content": "Nerves in the tongues of adult and immature rats were examined with respect to their permeability to exogenous cytochrome-c (mol wt 12,000) injected into the tongue. The distribution of cytochrome-c was determined in cryostat sections on the basis of the peroxidase activity of this protein. Nerves of 14-day-old rats were permeable to injected cytochrome-c. The larger nerves of older animals showed only localized accumulations of cytochrome-c reaction product both between and within axons adjacent to endoneurial blood vessels. Reaction product was not found, however, in association with blood vessels penetrating nerves of the tongue that were not within the limits of tracer spread. In the smallest nerve brances, thin linear strands of reaction product filled the interstices between the nerve fibers.", "contents": "Permeability barriers to cytochrome-c in nerves of adult and immature rats. Nerves in the tongues of adult and immature rats were examined with respect to their permeability to exogenous cytochrome-c (mol wt 12,000) injected into the tongue. The distribution of cytochrome-c was determined in cryostat sections on the basis of the peroxidase activity of this protein. Nerves of 14-day-old rats were permeable to injected cytochrome-c. The larger nerves of older animals showed only localized accumulations of cytochrome-c reaction product both between and within axons adjacent to endoneurial blood vessels. Reaction product was not found, however, in association with blood vessels penetrating nerves of the tongue that were not within the limits of tracer spread. In the smallest nerve brances, thin linear strands of reaction product filled the interstices between the nerve fibers."} {"id": "PMID:164140", "title": "The blood-brain barrier of the rat choroid plexus.", "content": "Following intravenous injection, cytochrome c traverses the capillary endothelium of the rat choroid plexus and permeates the perivascular space and the extracellular space between epithelial cells. The tracer is incorporated into pinocytotic vesicles adjacent to the lateral and basal plasmalemmas. Thereafter, cytochrome c is incorporated into multivesicular and dense bodies. Tracerladen vesicles were not found to fuse with the apical plasmalemma and cytochrome c was not discharged into the cerebral ventricles. Acid phosphatase activity of the choroidal epithelium after the administration of cytochrome c was greatly increased and localized in the same intracellular sites shown for cytochrome c. These data suggest that cytochrome c and possibly other proteins that penetrate the choroidal stroma are taken up by the choroidal epithelium and subsequently degraded in lysosomal vesicles. This heterolytic mechanism may be an important means for preventing the entry of certain substances such as proteins into CSF and subsequently into nervous tissue.", "contents": "The blood-brain barrier of the rat choroid plexus. Following intravenous injection, cytochrome c traverses the capillary endothelium of the rat choroid plexus and permeates the perivascular space and the extracellular space between epithelial cells. The tracer is incorporated into pinocytotic vesicles adjacent to the lateral and basal plasmalemmas. Thereafter, cytochrome c is incorporated into multivesicular and dense bodies. Tracerladen vesicles were not found to fuse with the apical plasmalemma and cytochrome c was not discharged into the cerebral ventricles. Acid phosphatase activity of the choroidal epithelium after the administration of cytochrome c was greatly increased and localized in the same intracellular sites shown for cytochrome c. These data suggest that cytochrome c and possibly other proteins that penetrate the choroidal stroma are taken up by the choroidal epithelium and subsequently degraded in lysosomal vesicles. This heterolytic mechanism may be an important means for preventing the entry of certain substances such as proteins into CSF and subsequently into nervous tissue."} {"id": "PMID:164141", "title": "Neuromuscular transmission in a mammalian preparation during exposure to enflurane.", "content": "The effects of enflurane on motor nerve terminals and muscle endplates were studied in the rat phrenic nerve-diaphragm preparation using standard microelectrode recording techniques. Muscle endplate interaction with enflurane was suggested by depression of the amplitude of miniature endplate potentials (MEPP's) without change in frequency, increased duration of MEPP's and endplate potentials (EPP's) increased threshold for generation of muscle action potentials, and inhibition of the endplate depolarization induced by succinylcholine. Evidence of nerve terminal effects of enflurane was limited to a greater relative decline of EPP amplitude during tetanus, indicative of failure to maintain transmitter output at rapid rates of stimulation. It is concluded that the depressant effect of enflurane on indirectly elicited muscle twitch is primarily due to an impairment of the action of muscle endplate on adjacent membrane; however, the relative importance of prejunctional depression, seen only during rapid nerve stimulation, cannot be assessed from the present data.", "contents": "Neuromuscular transmission in a mammalian preparation during exposure to enflurane. The effects of enflurane on motor nerve terminals and muscle endplates were studied in the rat phrenic nerve-diaphragm preparation using standard microelectrode recording techniques. Muscle endplate interaction with enflurane was suggested by depression of the amplitude of miniature endplate potentials (MEPP's) without change in frequency, increased duration of MEPP's and endplate potentials (EPP's) increased threshold for generation of muscle action potentials, and inhibition of the endplate depolarization induced by succinylcholine. Evidence of nerve terminal effects of enflurane was limited to a greater relative decline of EPP amplitude during tetanus, indicative of failure to maintain transmitter output at rapid rates of stimulation. It is concluded that the depressant effect of enflurane on indirectly elicited muscle twitch is primarily due to an impairment of the action of muscle endplate on adjacent membrane; however, the relative importance of prejunctional depression, seen only during rapid nerve stimulation, cannot be assessed from the present data."} {"id": "PMID:164143", "title": "Ectopic production of big ACTH in carcinoma of the lung. Its clinical usefulness as a biologic marker.", "content": "This report considers the potential usefulness of adrenocorticotropic hormone (ACTH) determinations in diagnosis and in prognosis for therapy of patients with carcinoma of the lung but without clinical Cushing's syndrome. The report is based on radioimmunoassay data from 129 patients, including 62 with lung cancers and 67 with nonmalignant pulmonary conditions. Elevated plasma ACTH was found in 21 of 24 patients with untreated cancer and the hormone was detected in tumor extracts and/or bronchial washings from the remaining 3. Elevation of plasma ACTH was found in only 10 of 38 treated patients. Absence of clinical Cushing's syndrome in spite of high plasma ACTH concentrations is explained by the observation that the predominant form of ectopic ACTH in plasma is immunoreactive but nonbioactive 'big' ACTH. Prolonged survival, for longer than 19 months, was observed in only 5 patients: all patients with low plasma ACTH after resection of the lung tumor and 2 of 3 patients with low plasma ACTH without therapy. ACTH was found in all available malignant tissue, primary and metastatic, from the lung carcinoma group,but not in normal lung or in 5 tumors metastatic to the lung. Of the 39 patients diagnosed initially to have chronic obstructive pulmonary disease, 14 showed plasma ACTH elevation. However, 3 of these patients with the highest concentrations subsequently manifested carcinoma or carcinoma in situ.", "contents": "Ectopic production of big ACTH in carcinoma of the lung. Its clinical usefulness as a biologic marker. This report considers the potential usefulness of adrenocorticotropic hormone (ACTH) determinations in diagnosis and in prognosis for therapy of patients with carcinoma of the lung but without clinical Cushing's syndrome. The report is based on radioimmunoassay data from 129 patients, including 62 with lung cancers and 67 with nonmalignant pulmonary conditions. Elevated plasma ACTH was found in 21 of 24 patients with untreated cancer and the hormone was detected in tumor extracts and/or bronchial washings from the remaining 3. Elevation of plasma ACTH was found in only 10 of 38 treated patients. Absence of clinical Cushing's syndrome in spite of high plasma ACTH concentrations is explained by the observation that the predominant form of ectopic ACTH in plasma is immunoreactive but nonbioactive 'big' ACTH. Prolonged survival, for longer than 19 months, was observed in only 5 patients: all patients with low plasma ACTH after resection of the lung tumor and 2 of 3 patients with low plasma ACTH without therapy. ACTH was found in all available malignant tissue, primary and metastatic, from the lung carcinoma group,but not in normal lung or in 5 tumors metastatic to the lung. Of the 39 patients diagnosed initially to have chronic obstructive pulmonary disease, 14 showed plasma ACTH elevation. However, 3 of these patients with the highest concentrations subsequently manifested carcinoma or carcinoma in situ."} {"id": "PMID:164144", "title": "Primary meningococcal pneumonia.", "content": "Three cases of pneumonia caused by Neisseria meningitidis group Y are reported. From the results of these cases, the following conclusions were made. N. meningitidis probably can cause serious infection without preceding blood stream invasion. Primary meningococcal pneumonia is not rare; it has no distinctive clinical presentation; and it may not be recognized by routine expectorated sputum cultures. In addition, it may be associated with recent influenzal and adenoviral infections. Lastly, meningococci of the serogroup Y are capable of causing serious disease. Antimicrobial susceptibility studies showed that all three group Y isolates were sensitive to sulfadiazine and rifampin as well as to penicillin, ampicillin, erythromycin, and chloramphenicol.", "contents": "Primary meningococcal pneumonia. Three cases of pneumonia caused by Neisseria meningitidis group Y are reported. From the results of these cases, the following conclusions were made. N. meningitidis probably can cause serious infection without preceding blood stream invasion. Primary meningococcal pneumonia is not rare; it has no distinctive clinical presentation; and it may not be recognized by routine expectorated sputum cultures. In addition, it may be associated with recent influenzal and adenoviral infections. Lastly, meningococci of the serogroup Y are capable of causing serious disease. Antimicrobial susceptibility studies showed that all three group Y isolates were sensitive to sulfadiazine and rifampin as well as to penicillin, ampicillin, erythromycin, and chloramphenicol."} {"id": "PMID:164146", "title": "[Chromatography of penicillins on a thin layer of sorbents. The utilization of \"Silufol\" plates].", "content": "Carbon metabolism of P. chrysogenum under conditions of periodical addition of the nutrients was studied. It was found that a proper rate of the carbon source addition to the culture was of significant importance for intensive biosynthesis. The use of carbon for the energetic and constructive needs was not the same at different fermentation periods.", "contents": "[Chromatography of penicillins on a thin layer of sorbents. The utilization of \"Silufol\" plates]. Carbon metabolism of P. chrysogenum under conditions of periodical addition of the nutrients was studied. It was found that a proper rate of the carbon source addition to the culture was of significant importance for intensive biosynthesis. The use of carbon for the energetic and constructive needs was not the same at different fermentation periods."} {"id": "PMID:164147", "title": "[Use of coulometric titration for elucidating the mechanism of the oxidation of 6-APA alkaline breakdown products by halogens].", "content": "Penaldinic acid and penicillamine were formed on alkali decomposition (1 N NaOH) of 6-APA for 20 minutes at room temperature, penicillamine being completely oxidized to disulphide by the air oxygen. Coulometric titration of the alkali decomposition products showed that generated chlorine in 0.5 N HCl solution or bromine in a week acid solution of KBr oxidized them with participation of 7 electrones. Generated iodine did not practically oxidize the 6-APA decomposition products during the coulometric titration.", "contents": "[Use of coulometric titration for elucidating the mechanism of the oxidation of 6-APA alkaline breakdown products by halogens]. Penaldinic acid and penicillamine were formed on alkali decomposition (1 N NaOH) of 6-APA for 20 minutes at room temperature, penicillamine being completely oxidized to disulphide by the air oxygen. Coulometric titration of the alkali decomposition products showed that generated chlorine in 0.5 N HCl solution or bromine in a week acid solution of KBr oxidized them with participation of 7 electrones. Generated iodine did not practically oxidize the 6-APA decomposition products during the coulometric titration."} {"id": "PMID:164154", "title": "Immunoglobulin deposits in lepromatous leprosy skin. Presence of deposits in apparently uninvolved skin and occurrence of serum antiepithelial antibodies.", "content": "Immunoglobulin deposits were detected in ten of 13 biopsy specimens from apparently uninvolved skin of patients with lepromatous leprosy. There were deposits of IgM at the dermoepidermal junction in the skin of five patients, and deposits of IgM along the dermal collagen and elastic fibers in the skin of the other five. The deposits were eluted with acid buffers and high molarity salt solution. Circulating IgG antibodies to intercellular substance of epithelial cells, similar to those present in pemphigus vulgaris, were found in 25% of patients with lepromatous leprosy who were studied. These antibodies appeared to be different from the skin-bound immunoglobulin deposits.", "contents": "Immunoglobulin deposits in lepromatous leprosy skin. Presence of deposits in apparently uninvolved skin and occurrence of serum antiepithelial antibodies. Immunoglobulin deposits were detected in ten of 13 biopsy specimens from apparently uninvolved skin of patients with lepromatous leprosy. There were deposits of IgM at the dermoepidermal junction in the skin of five patients, and deposits of IgM along the dermal collagen and elastic fibers in the skin of the other five. The deposits were eluted with acid buffers and high molarity salt solution. Circulating IgG antibodies to intercellular substance of epithelial cells, similar to those present in pemphigus vulgaris, were found in 25% of patients with lepromatous leprosy who were studied. These antibodies appeared to be different from the skin-bound immunoglobulin deposits."} {"id": "PMID:164155", "title": "Subclinical neuropathy at \"safe\" levels of lead exposure.", "content": "Electrophysiological methods revealed subclinical neuropathy in 26 workers, exposed from 1 to 17 years to lead and whose blood lead (PbB) values had never exceeded 70mu/100ml, as ascertained by checking the monitor reports of the factory and by careful exposure history. The PbB determinations had been tested repeatedly and had been found valid. The main findings were slowing of the maximal motor conduction velocities of the median and ulnar nerves and particularly the conduction velocity of the slower fibers of the ulnar nerve. Electromyographical abnormalities comprised fibrillations, diminution of the number of motor units on maximal contraction, and an abnormally long duration of the units. Earlier similar measurements from heavily exposed workers had been even more abnormal. Thus, a dose-response relationship exists on a group basis. Since the regular monitoring of PbBs in most workers during their entire period of exposure excludes the possibility of a body burden out of proportion to the PbB slight neurological damage is produced at exposures hitherto regarded as quite safe.", "contents": "Subclinical neuropathy at \"safe\" levels of lead exposure. Electrophysiological methods revealed subclinical neuropathy in 26 workers, exposed from 1 to 17 years to lead and whose blood lead (PbB) values had never exceeded 70mu/100ml, as ascertained by checking the monitor reports of the factory and by careful exposure history. The PbB determinations had been tested repeatedly and had been found valid. The main findings were slowing of the maximal motor conduction velocities of the median and ulnar nerves and particularly the conduction velocity of the slower fibers of the ulnar nerve. Electromyographical abnormalities comprised fibrillations, diminution of the number of motor units on maximal contraction, and an abnormally long duration of the units. Earlier similar measurements from heavily exposed workers had been even more abnormal. Thus, a dose-response relationship exists on a group basis. Since the regular monitoring of PbBs in most workers during their entire period of exposure excludes the possibility of a body burden out of proportion to the PbB slight neurological damage is produced at exposures hitherto regarded as quite safe."} {"id": "PMID:164156", "title": "Synovial sarcoma.", "content": "Of 34 cases with synovial sarcoma, the five-year survival rate was 36%. A high local recurrence rate results when local excision is performed. Wide excision which may necessitate amputation is the treatment of choice. Prophylactic and even therapeutic node dissections are ineffective in increasing survival because of the disease. Evaluation of radiation therapy was impossible, although some patients obtained significant paliation. Adriamycin appears to have a tumoricidal effect and provided clinically significant responses in several patients.", "contents": "Synovial sarcoma. Of 34 cases with synovial sarcoma, the five-year survival rate was 36%. A high local recurrence rate results when local excision is performed. Wide excision which may necessitate amputation is the treatment of choice. Prophylactic and even therapeutic node dissections are ineffective in increasing survival because of the disease. Evaluation of radiation therapy was impossible, although some patients obtained significant paliation. Adriamycin appears to have a tumoricidal effect and provided clinically significant responses in several patients."} {"id": "PMID:164157", "title": "The effect of puromycin and cycloheximide on vacuole formation and exocytosis in Tetrahymena pyriformis GL-9.", "content": "It has been shown that both puromycin and cycloheximide, at concentrations of 434 and 100 mug/ml respectively, produce a marked inhibition of vacuole formation and exocytosis in Tetrahymena pyriformis GL-9. These effects were analysed in a quantitative manner. At the same time as these inhibitions occurred the incorporation of 1-C14 leucine into trichloroacetic acid precipitable material was inhibited by 90% and 100% respectively over a 40 min period. This inhibition of protein synthesis by cycloheximide occurred almost immediately, whereas the inhibition of vacuole formation and egestion was delayed. The results suggested that the latter processes were dependent upon a continuing supply of proteinaceous material, of which there was only a small store within the cell. Cycloheximide inhibited exocytosis completely -nder the conditions employed (with 100% inhibition of protein synthesis) whereas puromycin (with a 90% inhibition of protein synthesis) only inhibited it by about 50%. This suggested that the amount of newly synthesized protein required for the exocytic egestion process was very small in relation to the total cell requirement for protein synthesis. The entry of both inhibitors into the cell was by means other than vacuole formation. Puromycin appeared to have some effect on vacuole formation which was unconnected with protein synthesis. Microscopic observations of living cells indicated that oral apparatus function and endocytic vacuole formation were probably both affected by the inhibitors. Chloramphenicol, at 200 mug/ml, had little effect on vacuole formation by starved cells with an exposure of an hour. The uptake of 1-C14 leucine from the growth medium was found to be a selective process, giving a concentration of about 2000 times into the cells over a 1 hr period. The results are discussed", "contents": "The effect of puromycin and cycloheximide on vacuole formation and exocytosis in Tetrahymena pyriformis GL-9. It has been shown that both puromycin and cycloheximide, at concentrations of 434 and 100 mug/ml respectively, produce a marked inhibition of vacuole formation and exocytosis in Tetrahymena pyriformis GL-9. These effects were analysed in a quantitative manner. At the same time as these inhibitions occurred the incorporation of 1-C14 leucine into trichloroacetic acid precipitable material was inhibited by 90% and 100% respectively over a 40 min period. This inhibition of protein synthesis by cycloheximide occurred almost immediately, whereas the inhibition of vacuole formation and egestion was delayed. The results suggested that the latter processes were dependent upon a continuing supply of proteinaceous material, of which there was only a small store within the cell. Cycloheximide inhibited exocytosis completely -nder the conditions employed (with 100% inhibition of protein synthesis) whereas puromycin (with a 90% inhibition of protein synthesis) only inhibited it by about 50%. This suggested that the amount of newly synthesized protein required for the exocytic egestion process was very small in relation to the total cell requirement for protein synthesis. The entry of both inhibitors into the cell was by means other than vacuole formation. Puromycin appeared to have some effect on vacuole formation which was unconnected with protein synthesis. Microscopic observations of living cells indicated that oral apparatus function and endocytic vacuole formation were probably both affected by the inhibitors. Chloramphenicol, at 200 mug/ml, had little effect on vacuole formation by starved cells with an exposure of an hour. The uptake of 1-C14 leucine from the growth medium was found to be a selective process, giving a concentration of about 2000 times into the cells over a 1 hr period. The results are discussed"} {"id": "PMID:164160", "title": "Stable polypeptides associated with the 250S mengovirus-induced RNA polymerase structure.", "content": "One host polypeptide (40,000 daltons) synthesized prior to infection is associated with the 250S RNA polymerase structure partially purified by a combination of velocity sedimentation and isopycnic separation. A series of pulse-chase experiments have shown that a 56,000 dalton polypeptide made during the eclipse phase of infection is inserted into the 250S viral RNA polymerase structure. This 56,000 dalton polypeptide is bound in a stable manner since labeled 56,000 dalton polypeptide is not removed from the 250S polymerase structure by a 2-hour chase (3 to 5 hours after infection) and it is the major labeled polypeptide species remaining. However, the 56,000 dalton polypeptide (viral-specific polypeptide E) made at 4 hours after infection is not present in the 250S polymerase structure following a 50 minue chase. Levels of cycloheximide which inhibit protein synthesis 95 per cent in the infected cell have no effect on the amount of viral-specific RNA polymerase activity (in vitro) when the inhibitor is added for 30 minutes at the time of maximum rate of viral RNA synthesis in whole cells. These inhibitor studies support the hypothesis that the viral-specific RNA polymerase polypeptide may be a stable polypeptide that is not rapidly turning over in the infected cell. In view of these results the stable 56,000 dalton polypeptide (polypeptide E) made early in infection may be a candidate for the viral-specific polymerase polypeptide.", "contents": "Stable polypeptides associated with the 250S mengovirus-induced RNA polymerase structure. One host polypeptide (40,000 daltons) synthesized prior to infection is associated with the 250S RNA polymerase structure partially purified by a combination of velocity sedimentation and isopycnic separation. A series of pulse-chase experiments have shown that a 56,000 dalton polypeptide made during the eclipse phase of infection is inserted into the 250S viral RNA polymerase structure. This 56,000 dalton polypeptide is bound in a stable manner since labeled 56,000 dalton polypeptide is not removed from the 250S polymerase structure by a 2-hour chase (3 to 5 hours after infection) and it is the major labeled polypeptide species remaining. However, the 56,000 dalton polypeptide (viral-specific polypeptide E) made at 4 hours after infection is not present in the 250S polymerase structure following a 50 minue chase. Levels of cycloheximide which inhibit protein synthesis 95 per cent in the infected cell have no effect on the amount of viral-specific RNA polymerase activity (in vitro) when the inhibitor is added for 30 minutes at the time of maximum rate of viral RNA synthesis in whole cells. These inhibitor studies support the hypothesis that the viral-specific RNA polymerase polypeptide may be a stable polypeptide that is not rapidly turning over in the infected cell. In view of these results the stable 56,000 dalton polypeptide (polypeptide E) made early in infection may be a candidate for the viral-specific polymerase polypeptide."} {"id": "PMID:164161", "title": "Some investigations on the adjuvant mechanism of DEAE dextran.", "content": "In vitro it was shown that adsorption of inactivated FMDV onto DEAE-D kieselgur columns did not occur in the presence of 0.1--0.15M NaCl. These NaCl concentrations are present in DEAE-D/FMDV vaccines and in the tissues of animals. Therefore, adsorption of virus antigen does not appear to be responsible for the adjuvant effect of DEAE-D. In pigs it was demonstrated that DEAE-D exerts its optimal adjuvant effect, as measured by the formation of neutralizing antibodies and protection against challenge infection, when injected together with inactivated FMDV as vaccine. Apart from this, a good adjuvant effect (group immunity 75--100 per cent) was evoked in about one half and a moderate effect (group immunity 50--70 per cent) in about a quarter of the inoculated animals even if DEAE-D was separately injected locally and temporally from the inactivated virus. With regard to immunity it apparently does not matter whether DEAE-D or inactivated virus was given first, but an interval of 48 hours or 4 days between injection seemed to be more favourable than one of 24 hours. With regard to the formation of neutralizing antibodies the situation is comparable to that of immunity with the exception that a time interval of 24 hours between the application of DEAE-D and inactivated virus or vice versa was as good as that of 48 hours or 4 days. The results are discussed in regard to the possible mechanism of the adjuvant effect of DEAE-D on the cellular level.", "contents": "Some investigations on the adjuvant mechanism of DEAE dextran. In vitro it was shown that adsorption of inactivated FMDV onto DEAE-D kieselgur columns did not occur in the presence of 0.1--0.15M NaCl. These NaCl concentrations are present in DEAE-D/FMDV vaccines and in the tissues of animals. Therefore, adsorption of virus antigen does not appear to be responsible for the adjuvant effect of DEAE-D. In pigs it was demonstrated that DEAE-D exerts its optimal adjuvant effect, as measured by the formation of neutralizing antibodies and protection against challenge infection, when injected together with inactivated FMDV as vaccine. Apart from this, a good adjuvant effect (group immunity 75--100 per cent) was evoked in about one half and a moderate effect (group immunity 50--70 per cent) in about a quarter of the inoculated animals even if DEAE-D was separately injected locally and temporally from the inactivated virus. With regard to immunity it apparently does not matter whether DEAE-D or inactivated virus was given first, but an interval of 48 hours or 4 days between injection seemed to be more favourable than one of 24 hours. With regard to the formation of neutralizing antibodies the situation is comparable to that of immunity with the exception that a time interval of 24 hours between the application of DEAE-D and inactivated virus or vice versa was as good as that of 48 hours or 4 days. The results are discussed in regard to the possible mechanism of the adjuvant effect of DEAE-D on the cellular level."} {"id": "PMID:164162", "title": "Growth of SV 40, adeno 7 and SV 40-adeno 7 viruses in monkey and human cells at 29 degrees and 37 degrees C.", "content": "Adeno 7 virus replicated well in human diploid (LEP) cells but only to a low degree in green monkey kidney (GMK) cells at 37 degrees C; it did not replicate in either system at 29 degrees C. At 37 degrees C SV 40 virus replicated well in GMK cells but only moderately in LEP cells; at 29 degrees C it did not replicate in either system. SV 40-adeno 7 hybrid grew in both GMK cells and LEP cells at 37 degrees C. At 29 degrees C this virus replicated in GMK cells but not in LEP cells. While the formation of V-antigen generally corresponded to the infectious virus production in the respective system, considerable differences were encountered in the T-antigens production. Adeno 7 T-antigen was detected earlier and in a higher percentage of GMK cells than in the fully permissive LEP cells and its formation was only slightly influenced by the incubation temperature. SV 40 T-antigen was more efficiently formed in GMK cells than in LEP cells. At 29 degrees C SV 40 T-antigen was only found in GMK cells and was detected later than at 37 degrees C. The difference in the formation of SV 40 T-antigen in GMK cells infected with SV 40 and SV 40-adeno 7 hybrid virus was further analyzed. The results obtained suggest that an early step of the virus-cell interaction, but neither virus attachment nor penetration, was involved.", "contents": "Growth of SV 40, adeno 7 and SV 40-adeno 7 viruses in monkey and human cells at 29 degrees and 37 degrees C. Adeno 7 virus replicated well in human diploid (LEP) cells but only to a low degree in green monkey kidney (GMK) cells at 37 degrees C; it did not replicate in either system at 29 degrees C. At 37 degrees C SV 40 virus replicated well in GMK cells but only moderately in LEP cells; at 29 degrees C it did not replicate in either system. SV 40-adeno 7 hybrid grew in both GMK cells and LEP cells at 37 degrees C. At 29 degrees C this virus replicated in GMK cells but not in LEP cells. While the formation of V-antigen generally corresponded to the infectious virus production in the respective system, considerable differences were encountered in the T-antigens production. Adeno 7 T-antigen was detected earlier and in a higher percentage of GMK cells than in the fully permissive LEP cells and its formation was only slightly influenced by the incubation temperature. SV 40 T-antigen was more efficiently formed in GMK cells than in LEP cells. At 29 degrees C SV 40 T-antigen was only found in GMK cells and was detected later than at 37 degrees C. The difference in the formation of SV 40 T-antigen in GMK cells infected with SV 40 and SV 40-adeno 7 hybrid virus was further analyzed. The results obtained suggest that an early step of the virus-cell interaction, but neither virus attachment nor penetration, was involved."} {"id": "PMID:164165", "title": "Local cooling in myasthenia. Improvement of neuromuscular failure.", "content": "Weak myasthenic muscles were tested by nerve stimulation both at normal temperature and after local cooling that was accomplished by exposing the skin to ice bags or cold paraffin oil. Reduction of intramuscular temperature from 35 C to 28 C increased the voltage of the bellytendon electrical response, the force of the tetanus elicited by 10/sec or 20/sec nerve stimulation. The myasthenic decrement of successive muscle responses was less marked after cooling, as were \"delayed rundown\" and \"postactivation exhaustion.\" All these effects were reversed on rewarming the muscle. The abnormal neuromuscular jitter in motor-unit components was also reduced by local cooling. These observations may explain why diagnostic application of repetitive stimulation may be false-negative; muscle temperature must be controlled.", "contents": "Local cooling in myasthenia. Improvement of neuromuscular failure. Weak myasthenic muscles were tested by nerve stimulation both at normal temperature and after local cooling that was accomplished by exposing the skin to ice bags or cold paraffin oil. Reduction of intramuscular temperature from 35 C to 28 C increased the voltage of the bellytendon electrical response, the force of the tetanus elicited by 10/sec or 20/sec nerve stimulation. The myasthenic decrement of successive muscle responses was less marked after cooling, as were \"delayed rundown\" and \"postactivation exhaustion.\" All these effects were reversed on rewarming the muscle. The abnormal neuromuscular jitter in motor-unit components was also reduced by local cooling. These observations may explain why diagnostic application of repetitive stimulation may be false-negative; muscle temperature must be controlled."} {"id": "PMID:164166", "title": "The mechanism of neuromuscular fatigue. A study of mammalian muscle using excitation-contraction uncoupling.", "content": "Neuromuscular transmission failure was measured during rapid repetitive stimulation of the rat hemidiaphragm in vitro after excitation-contraction uncoupling by hyperosmolar glycerol, washing, and dantrolene sodium. Observations of resting membrane, miniature endplate, action, and endplate potentials (epps) showed that neuromuscular transmission failure occurred during stimulation because of a decrement of the epp. This decrement was due both to a reduced number of quanta released and to a variable reduction of quantal size. The time course of these events was studied, and limited observations were made on recovery. Observations of the difference between the epp decrement of cut muscle and of partially curarized muscle suggest a prejunctional action of curare.", "contents": "The mechanism of neuromuscular fatigue. A study of mammalian muscle using excitation-contraction uncoupling. Neuromuscular transmission failure was measured during rapid repetitive stimulation of the rat hemidiaphragm in vitro after excitation-contraction uncoupling by hyperosmolar glycerol, washing, and dantrolene sodium. Observations of resting membrane, miniature endplate, action, and endplate potentials (epps) showed that neuromuscular transmission failure occurred during stimulation because of a decrement of the epp. This decrement was due both to a reduced number of quanta released and to a variable reduction of quantal size. The time course of these events was studied, and limited observations were made on recovery. Observations of the difference between the epp decrement of cut muscle and of partially curarized muscle suggest a prejunctional action of curare."} {"id": "PMID:164167", "title": "Neurological sequelae of malignant external otitis.", "content": "The neurological sequelae of malignant external otitis (MEO) form a characteristic syndrome. Following Pseudomonas external otitis, usually in an elderly, diabetic patient, either isolated facial nerve paralysis or multiple cranial nerve palsies develop. Once extensive neurological signs have developed, recovery rarely occurs. We saw a patient with MEO and multiple cranial nerve palsies who recovered following an extended course of gentamicin sulfate and carbenicillin disodium therapy.", "contents": "Neurological sequelae of malignant external otitis. The neurological sequelae of malignant external otitis (MEO) form a characteristic syndrome. Following Pseudomonas external otitis, usually in an elderly, diabetic patient, either isolated facial nerve paralysis or multiple cranial nerve palsies develop. Once extensive neurological signs have developed, recovery rarely occurs. We saw a patient with MEO and multiple cranial nerve palsies who recovered following an extended course of gentamicin sulfate and carbenicillin disodium therapy."} {"id": "PMID:164168", "title": "Neurologic disorders following surgery for peptic ulcer disease.", "content": "The neurologic status of 2,000 veterans who had had surgery for peptic ulcer between 1952 and 1957 was evaluated. In 1970, a total of 156 of these men were examined, 97 of whom had procedures that disrupted the normal continuity of the upper gastrointestinal tract. Twenty-one had neurologic disorders, including 17 patients with peripheral neuropathies. Procedures bypassing the ampulla of Vater were performed in 15 of these. The only detected factor associated with neurologic manifestations was weight loss since surgery. A mortality study of the total population revealed 865 patients had died by the end of 1973. There were seven deaths attributed to neurologic causes, one in a patient with amyotrophic lateral sclerosis and one in another with spinal paralysis. All seven were among the 70% of the deceased who had had surgery that disrupted the continuity of the upper gastrointestinal tract. Thus, we conclude that the type of surgery influenced the likelihood of neurologic complications, but at least for motor neuron disease, the increased risk was not appreciable.", "contents": "Neurologic disorders following surgery for peptic ulcer disease. The neurologic status of 2,000 veterans who had had surgery for peptic ulcer between 1952 and 1957 was evaluated. In 1970, a total of 156 of these men were examined, 97 of whom had procedures that disrupted the normal continuity of the upper gastrointestinal tract. Twenty-one had neurologic disorders, including 17 patients with peripheral neuropathies. Procedures bypassing the ampulla of Vater were performed in 15 of these. The only detected factor associated with neurologic manifestations was weight loss since surgery. A mortality study of the total population revealed 865 patients had died by the end of 1973. There were seven deaths attributed to neurologic causes, one in a patient with amyotrophic lateral sclerosis and one in another with spinal paralysis. All seven were among the 70% of the deceased who had had surgery that disrupted the continuity of the upper gastrointestinal tract. Thus, we conclude that the type of surgery influenced the likelihood of neurologic complications, but at least for motor neuron disease, the increased risk was not appreciable."} {"id": "PMID:164169", "title": "Prognosis of malignant tumors of the parotid gland with facial paralysis.", "content": "A parotid malignant tumor with spontaneous facial nerve involvement is a serious prognostic sign. Of 34 patients reported, 29 have been followed for at least five years. In this group, 20 are dead of disease (one at five years), one is dead of other causes (at seven years), one is living with disease, and seven are free of disease. Four of these seven cases have been followed for more than ten years, with two being free of disease for 12 years. Thus, it is not a hopeless situation, as some studies have shown, and not a contraindication to combined radical surgery and radiotherapy treatment for cure if not palliation.", "contents": "Prognosis of malignant tumors of the parotid gland with facial paralysis. A parotid malignant tumor with spontaneous facial nerve involvement is a serious prognostic sign. Of 34 patients reported, 29 have been followed for at least five years. In this group, 20 are dead of disease (one at five years), one is dead of other causes (at seven years), one is living with disease, and seven are free of disease. Four of these seven cases have been followed for more than ten years, with two being free of disease for 12 years. Thus, it is not a hopeless situation, as some studies have shown, and not a contraindication to combined radical surgery and radiotherapy treatment for cure if not palliation."} {"id": "PMID:164171", "title": "Protein deficiency in carbon tetrachloride-induced hepatic lesions.", "content": "The influence of protein deficiency on the hepatotoxicity of carbon tetrachloride (CCl4) was investigated in a group of rhesus monkeys. Animals fed a protein-rich diet served as controls. The results indicate that protein-deficiency protects the liver against acute hepatotoxicity of this drug. The protective effect is abolished if the animals are administered phenobarbital prior to the administration of CCl4. The protective action is due to a reduction, in protein deficiency, of the endoplasmic reticulum associated enzymes involved in hepatotoxicity of CCl4. Repeated administration of CCl4, which induces hepatic regeneration, resulted in disappearance of fat from periportal cells in protein-deficient animals. The regenerating cells (because of their better enzyme system) acquire \"nutritional autonomy\" and are thus able to synthesize adequate amounts of lipoproteins for mobilization of liver triglycerides.", "contents": "Protein deficiency in carbon tetrachloride-induced hepatic lesions. The influence of protein deficiency on the hepatotoxicity of carbon tetrachloride (CCl4) was investigated in a group of rhesus monkeys. Animals fed a protein-rich diet served as controls. The results indicate that protein-deficiency protects the liver against acute hepatotoxicity of this drug. The protective effect is abolished if the animals are administered phenobarbital prior to the administration of CCl4. The protective action is due to a reduction, in protein deficiency, of the endoplasmic reticulum associated enzymes involved in hepatotoxicity of CCl4. Repeated administration of CCl4, which induces hepatic regeneration, resulted in disappearance of fat from periportal cells in protein-deficient animals. The regenerating cells (because of their better enzyme system) acquire \"nutritional autonomy\" and are thus able to synthesize adequate amounts of lipoproteins for mobilization of liver triglycerides."} {"id": "PMID:164172", "title": "Systemic lupus erythematosus.", "content": "Recent investigations in systemic lupus erythematosus (SLE) have disclosed the presence of paramyxo-virus-like nucleocapsids in the cytoplasm of renal endothelial cells of patients with this disease. Elaborate techniques have failed to demonstrate conclusively that these are indeed viruses. Concomitantly, there is increasing evidence that SLE patients have defective cell-mediated-immunity. A 3-year-old child with SLE exhibited clinical evidence of defective cellular immunity. At postmortem, paramyxoviruslike tubular structures were demonstrated in her kidneys. Additional findings included the presence of intracytoplasmic viral particles consistent morphologically with herpes simplex virus in neurons from the lateral geniculate body and numerous \"nuclear bodies\" in neurons and glial cells. A dysplastic thymus gland demonstrated virtual absence of lymphocytes and was devoid of Hassall corpuscles, unlike the thymus usually seen in SLE.", "contents": "Systemic lupus erythematosus. Recent investigations in systemic lupus erythematosus (SLE) have disclosed the presence of paramyxo-virus-like nucleocapsids in the cytoplasm of renal endothelial cells of patients with this disease. Elaborate techniques have failed to demonstrate conclusively that these are indeed viruses. Concomitantly, there is increasing evidence that SLE patients have defective cell-mediated-immunity. A 3-year-old child with SLE exhibited clinical evidence of defective cellular immunity. At postmortem, paramyxoviruslike tubular structures were demonstrated in her kidneys. Additional findings included the presence of intracytoplasmic viral particles consistent morphologically with herpes simplex virus in neurons from the lateral geniculate body and numerous \"nuclear bodies\" in neurons and glial cells. A dysplastic thymus gland demonstrated virtual absence of lymphocytes and was devoid of Hassall corpuscles, unlike the thymus usually seen in SLE."} {"id": "PMID:164173", "title": "Calcified mixed malignant tumor of the liver.", "content": "Two adult patients died from mixed hepatic tumors of the liver with metastasis. The outstanding findings in both patients were a long clinical course, roentgenologically identifiable calcification of the tumors, and, in one, hypertrophic osteoarthropathy and spider angiomas. Mixed hepatic tumors are rare in adults, only 14 possible previous cases have come to our attention. The mixed hepatic tumors of adults are morphologically different from the more common mixed hepatoblastomas of infancy and childhood. Calcification in a slow-growing tumor in an adult without cirrhosis may indicate a mixed hepatic tumor.", "contents": "Calcified mixed malignant tumor of the liver. Two adult patients died from mixed hepatic tumors of the liver with metastasis. The outstanding findings in both patients were a long clinical course, roentgenologically identifiable calcification of the tumors, and, in one, hypertrophic osteoarthropathy and spider angiomas. Mixed hepatic tumors are rare in adults, only 14 possible previous cases have come to our attention. The mixed hepatic tumors of adults are morphologically different from the more common mixed hepatoblastomas of infancy and childhood. Calcification in a slow-growing tumor in an adult without cirrhosis may indicate a mixed hepatic tumor."} {"id": "PMID:164174", "title": "Experimental egg-transmission of avian reovirus.", "content": "Two experiments with an avian reovirus (FDO isolant), serologically identical to the Fahey-Crawley and WVU 2937 isolants, provided conclusive proof that egg-transmission can occur. In the first experiment, 4-day-old chicken embryos were inoculated into the yolk sac with serial dilutions of virus and subsequently hatched. High virus doses killed all embryos, whereas low doses (14 or less plaque-forming units) allowed some embryos to hatch normally although infected. In the second experiment, virus was administered by the nasal, esophageal, and tracheal routes to twenty 15-month-old breeders. Eggs from -6 to 21 days and 58 to 64 days postinoculation were incubated. Three newly hatched chicks from eggs laid on successive days (17, 18, and 19 days postinoculation) and one infertile egg (61 days postinoculation) were found infected. Active infection, as judged by virus isolations from cloacal swabs, was over by the 17th day postinoculation.", "contents": "Experimental egg-transmission of avian reovirus. Two experiments with an avian reovirus (FDO isolant), serologically identical to the Fahey-Crawley and WVU 2937 isolants, provided conclusive proof that egg-transmission can occur. In the first experiment, 4-day-old chicken embryos were inoculated into the yolk sac with serial dilutions of virus and subsequently hatched. High virus doses killed all embryos, whereas low doses (14 or less plaque-forming units) allowed some embryos to hatch normally although infected. In the second experiment, virus was administered by the nasal, esophageal, and tracheal routes to twenty 15-month-old breeders. Eggs from -6 to 21 days and 58 to 64 days postinoculation were incubated. Three newly hatched chicks from eggs laid on successive days (17, 18, and 19 days postinoculation) and one infertile egg (61 days postinoculation) were found infected. Active infection, as judged by virus isolations from cloacal swabs, was over by the 17th day postinoculation."} {"id": "PMID:164176", "title": "Horizontal transmission of turkey herpesvirus to chickens. IV. Viral maturation in the feather follicle epithelium.", "content": "An experimental line of White Leghorns (WSU-VS) and a commerical line inoculated with turkey herpesvirus (HVT) at 1 or 8 weeks old did not differ in the occurrence of infectious cell-free HVT in their feather-tip preparations (FT-HVT). The birds examined at 2 weeks postinoculation (PI) were always positive for FT-HVT regardless of age at virus inoculation, dose of HVT inoculated, or genetic line of chickens, whereas only a few were positive at 4 weeks and none at 6 weeks PI.", "contents": "Horizontal transmission of turkey herpesvirus to chickens. IV. Viral maturation in the feather follicle epithelium. An experimental line of White Leghorns (WSU-VS) and a commerical line inoculated with turkey herpesvirus (HVT) at 1 or 8 weeks old did not differ in the occurrence of infectious cell-free HVT in their feather-tip preparations (FT-HVT). The birds examined at 2 weeks postinoculation (PI) were always positive for FT-HVT regardless of age at virus inoculation, dose of HVT inoculated, or genetic line of chickens, whereas only a few were positive at 4 weeks and none at 6 weeks PI."} {"id": "PMID:164175", "title": "Localization of avian reovirus (FDO isolant) in tissues of mature chickens.", "content": "Mature hens were exposed to a reovirus (FDO isolant) serologically related to the viral arthritis agent. Examination of 23 tissues from the respiratory, alimentary, and reproductive tracts and tendons from the hock joint revealed widespread infection 4 days after inoculation via the respiratory and alimentary tracts. By 14-15 days, infection had largely subsided but was still detectable in the tendons, oviduct, and alimentary tract of some birds. No infection was found at 30 days. Virus isolation attempts in chick kidney cultures were more reliable than fluorescent-antibody tests for detecting infection. None of 156 chicks hatched from eggs laid between 12 and 33 days postinoculation were infected.", "contents": "Localization of avian reovirus (FDO isolant) in tissues of mature chickens. Mature hens were exposed to a reovirus (FDO isolant) serologically related to the viral arthritis agent. Examination of 23 tissues from the respiratory, alimentary, and reproductive tracts and tendons from the hock joint revealed widespread infection 4 days after inoculation via the respiratory and alimentary tracts. By 14-15 days, infection had largely subsided but was still detectable in the tendons, oviduct, and alimentary tract of some birds. No infection was found at 30 days. Virus isolation attempts in chick kidney cultures were more reliable than fluorescent-antibody tests for detecting infection. None of 156 chicks hatched from eggs laid between 12 and 33 days postinoculation were infected."} {"id": "PMID:164177", "title": "Characteristics of three stains of avian adenoviruses isolated in Queensland. I. Biological properties.", "content": "Three strains of avian adenovirus were isolated and studied in cell cultures, chicken embryos, and chickens. One strain (ADAM-1) was isolated from the bursa of Fabricius of a chicken with Marek's disease, and the others (ADAM-2 and ADAM-3) from one-day-old chicks with respiratory signs. Experimentally, ADAM-1 produced no clinical signs or lesions except atrophy of the bursa of Fabricius. ADAM-2 caused mild respiratory signs in young chickens when inoculated intratracheally. The behavior of the three viruses in cell cultures and chick embryos was similar to that described for other avian adenoviruses (CELO). In a serological survey using the agar-gel precipitation test, 3-30% of sera tested gave a positive reaction.", "contents": "Characteristics of three stains of avian adenoviruses isolated in Queensland. I. Biological properties. Three strains of avian adenovirus were isolated and studied in cell cultures, chicken embryos, and chickens. One strain (ADAM-1) was isolated from the bursa of Fabricius of a chicken with Marek's disease, and the others (ADAM-2 and ADAM-3) from one-day-old chicks with respiratory signs. Experimentally, ADAM-1 produced no clinical signs or lesions except atrophy of the bursa of Fabricius. ADAM-2 caused mild respiratory signs in young chickens when inoculated intratracheally. The behavior of the three viruses in cell cultures and chick embryos was similar to that described for other avian adenoviruses (CELO). In a serological survey using the agar-gel precipitation test, 3-30% of sera tested gave a positive reaction."} {"id": "PMID:164178", "title": "Natural pox and herpes as a dual virus infection in chickens.", "content": "A natural dual viral infection was confirmed in chickens of University of Illinois Poultry Farm by histopathologic, immunologic, and electron-microscopic examination of formalin-fixed tracheal tissue. Histopathologic examination of the tracheal mucosa revealed eosinophilic cytoplasmic inclusions characteristic of fowlpox and intranuclear inclusions suggestive of Marek's disease. Treatment of the formalin-fixed tracheal tissue with peroxidase and fluorescent-labeled antibody against Marek's disease virus revealed specificity of the reaction. Electron microscopy showed viral particles of two morphologic forms, i.e., pox and herpes. A single cell having dual infection with herpes virus in the nucleus and pox virus in the cytoplasm was also encountered on electron-microscopic examination.", "contents": "Natural pox and herpes as a dual virus infection in chickens. A natural dual viral infection was confirmed in chickens of University of Illinois Poultry Farm by histopathologic, immunologic, and electron-microscopic examination of formalin-fixed tracheal tissue. Histopathologic examination of the tracheal mucosa revealed eosinophilic cytoplasmic inclusions characteristic of fowlpox and intranuclear inclusions suggestive of Marek's disease. Treatment of the formalin-fixed tracheal tissue with peroxidase and fluorescent-labeled antibody against Marek's disease virus revealed specificity of the reaction. Electron microscopy showed viral particles of two morphologic forms, i.e., pox and herpes. A single cell having dual infection with herpes virus in the nucleus and pox virus in the cytoplasm was also encountered on electron-microscopic examination."} {"id": "PMID:164200", "title": "[Biology of prostaglandins with reference to therapeutic aspects].", "content": "Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired \"target\" tissues are available.", "contents": "[Biology of prostaglandins with reference to therapeutic aspects]. Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired \"target\" tissues are available."} {"id": "PMID:164201", "title": "Hyperlipidaemia in children.", "content": "Hyperlipidaemia in children is most commonly expressed as hypercholesterolaemia. \"Normal values\" for serum cholesterol, if defined statistically, vary between communities, and levels of cholesterol in childhood above which an increased risk of coronary heart disease in adult life may be expected have not been firmly established. It is suggested that serum cholesterol concentration over 250 mg/dl (6.47 mmol/l) in a child over 1 year of age merits detailed investigation, including full lipoprotein analysis, and levels of serum cholesterol between230 and 250 mg/dl (5.95-6.47 mmol/l) should be repeated with further studies if indicated. Secondary hyperlipoproteinaemia rarely presents diagnostic problems but must always be excluded. The only primary hyperlipoproteinaemia likely to be encountered in childhood is familial hyperbetalipoproteinaemia in its common heterozygous form. The most effective means to date of lowering serum cholesterol in this condition is cholestyramine, but the long-term consequences of therapy are not known and treatment should at present be limited to children from high-risk families. Long-term follow-up is essential and until results of such studies are available population screening is unjustified.", "contents": "Hyperlipidaemia in children. Hyperlipidaemia in children is most commonly expressed as hypercholesterolaemia. \"Normal values\" for serum cholesterol, if defined statistically, vary between communities, and levels of cholesterol in childhood above which an increased risk of coronary heart disease in adult life may be expected have not been firmly established. It is suggested that serum cholesterol concentration over 250 mg/dl (6.47 mmol/l) in a child over 1 year of age merits detailed investigation, including full lipoprotein analysis, and levels of serum cholesterol between230 and 250 mg/dl (5.95-6.47 mmol/l) should be repeated with further studies if indicated. Secondary hyperlipoproteinaemia rarely presents diagnostic problems but must always be excluded. The only primary hyperlipoproteinaemia likely to be encountered in childhood is familial hyperbetalipoproteinaemia in its common heterozygous form. The most effective means to date of lowering serum cholesterol in this condition is cholestyramine, but the long-term consequences of therapy are not known and treatment should at present be limited to children from high-risk families. Long-term follow-up is essential and until results of such studies are available population screening is unjustified."} {"id": "PMID:164202", "title": "Priming of superhelical SV40 DNA by Escherichia coli RNA polymerase for in vitro DNA synthesis.", "content": "When closed circular SV40 DNA containing 58 negative superhelical turns is used as a template for RNA synthesis with Escherichia coli RNA polymerase, a fraction of the RNA product remains complexed with the DNA. The RNA in the complex is resistant to ribonuclease in high salt, and the Tm indicates that it is hydrogen bonded to the DNA. The mole ratio of RNA to DNA nucleotides in the complex ranges from 0.01 to 0.08; the RNA ranges in length from 80 to 600 nucleotides. The formation of the complex is dependent on the circular DNA being topologically underwound since no complex is formed when closed circular DNA containing zero superhelical turns is used as the template. The DNA-RNA complex can serve as a primer-template combination for in vitro DNA synthesis by E. coli DNA polymerase I. After synthesis with (alpha-32P)-labeled deoxyribonucleoside triphosphates followed by alkaline hydrolysis, the isolation of 32P-labeled ribonucleotides is evidence for a covalent linkage between the RNA and the DNA synthesized. During the in vitro DNA synthesis, the template is nicked at a low rate, and the nicked molecules support extensive DNA synthesis. This observation indicates that only limited synthesis can occur on unnicked molecules possibly owing to the topological constraints against unwinding of the helix. Possible models for in vivo priming of double-stranded DNA by E. coli RNA polymerase are discussed.", "contents": "Priming of superhelical SV40 DNA by Escherichia coli RNA polymerase for in vitro DNA synthesis. When closed circular SV40 DNA containing 58 negative superhelical turns is used as a template for RNA synthesis with Escherichia coli RNA polymerase, a fraction of the RNA product remains complexed with the DNA. The RNA in the complex is resistant to ribonuclease in high salt, and the Tm indicates that it is hydrogen bonded to the DNA. The mole ratio of RNA to DNA nucleotides in the complex ranges from 0.01 to 0.08; the RNA ranges in length from 80 to 600 nucleotides. The formation of the complex is dependent on the circular DNA being topologically underwound since no complex is formed when closed circular DNA containing zero superhelical turns is used as the template. The DNA-RNA complex can serve as a primer-template combination for in vitro DNA synthesis by E. coli DNA polymerase I. After synthesis with (alpha-32P)-labeled deoxyribonucleoside triphosphates followed by alkaline hydrolysis, the isolation of 32P-labeled ribonucleotides is evidence for a covalent linkage between the RNA and the DNA synthesized. During the in vitro DNA synthesis, the template is nicked at a low rate, and the nicked molecules support extensive DNA synthesis. This observation indicates that only limited synthesis can occur on unnicked molecules possibly owing to the topological constraints against unwinding of the helix. Possible models for in vivo priming of double-stranded DNA by E. coli RNA polymerase are discussed."} {"id": "PMID:164203", "title": "Cell surface changes correlated with density-dependent growth inhibition. Glycosaminoglycan metabolism in 3T3, SV3T3, and con A selected revertant cells.", "content": "A 35SO4-labeling/chromatography technique has been developed which facilitates quantitation of sulfated glycosaminoglycan (GAG) synthesis in mammalian cell cultures. The technique has been used to compare sulfated GAG biosynthesis, degradation, and turnover in three related cell lines with differing degrees of density-dependent inhibition of growth in vitro (Balb/c 3T3, SV3T3, and SV3T3 revertant cells). Viral transformation of Balb 3T3 cells is accompanied by a 2-5-fold decrease in cell associated sulfated GAG. SV3T3 revertant cells, which show partial reversion to low saturation density in vitro, show a 2.5-8-fold increase in cell-associated sulfated GAG compared to the parental SV3T3 cells from which they were selected. In addition, the distribution of 35SO4 and [3H]glucosamine among the different GAG species produced by SV3T3 revertant cells reverts so that it is similar to the distribution characteristic of untransformed 3T3 cells rather than SV3T3 cells. Mild trypsin treatment of 35SO4-labeled cells removed 68-84% of the cellular sulfated GAG, suggesting that at least this proportion of the total cellular sulfated GAG was located at the cell periphery. Removal of 35SO4-labeled cells from the Petri dish with a Ca2+ selective chelating agent revealed a fraction of the sulfated GAG that remained tightly bound to the Petri dish. A higher proportion of the total cell-associated sulfated GAG remained attached to the Petri dish in cultures of untransformed and revertant cells compared to that present in cultures of transformed cells. A role for sulfated GAG in density-dependent growth inhibition of fibroblast cultures is proposed and discussed in the light of the data obtained.", "contents": "Cell surface changes correlated with density-dependent growth inhibition. Glycosaminoglycan metabolism in 3T3, SV3T3, and con A selected revertant cells. A 35SO4-labeling/chromatography technique has been developed which facilitates quantitation of sulfated glycosaminoglycan (GAG) synthesis in mammalian cell cultures. The technique has been used to compare sulfated GAG biosynthesis, degradation, and turnover in three related cell lines with differing degrees of density-dependent inhibition of growth in vitro (Balb/c 3T3, SV3T3, and SV3T3 revertant cells). Viral transformation of Balb 3T3 cells is accompanied by a 2-5-fold decrease in cell associated sulfated GAG. SV3T3 revertant cells, which show partial reversion to low saturation density in vitro, show a 2.5-8-fold increase in cell-associated sulfated GAG compared to the parental SV3T3 cells from which they were selected. In addition, the distribution of 35SO4 and [3H]glucosamine among the different GAG species produced by SV3T3 revertant cells reverts so that it is similar to the distribution characteristic of untransformed 3T3 cells rather than SV3T3 cells. Mild trypsin treatment of 35SO4-labeled cells removed 68-84% of the cellular sulfated GAG, suggesting that at least this proportion of the total cellular sulfated GAG was located at the cell periphery. Removal of 35SO4-labeled cells from the Petri dish with a Ca2+ selective chelating agent revealed a fraction of the sulfated GAG that remained tightly bound to the Petri dish. A higher proportion of the total cell-associated sulfated GAG remained attached to the Petri dish in cultures of untransformed and revertant cells compared to that present in cultures of transformed cells. A role for sulfated GAG in density-dependent growth inhibition of fibroblast cultures is proposed and discussed in the light of the data obtained."} {"id": "PMID:164204", "title": "Relationship between fluorescence and conformation of epsilonNAD+ bound to dehydrogenases.", "content": "This work reports on the interaction of the fluorescent nicotinamide 1,N6-ethenoadenine dinucleotide (epsilonNAD+) with horse liver alcohol dehydrogenase, octopine dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase from different sources (yeast, lobster muscle, and rabbit muscle). The coenzyme fluorescence is enhanced by a factor of 10-13 in all systems investigated. It is shown that this enhancement cannot be due to changes in the polarity of the environment upon binding, and that it must be rather ascribed to structural properties of the bound coenzyme. Although dynamic factors could also be important for inducing changes in the quantum yield of epsilonNAD+ fluorescence, the close similarity of the fluorescence enhancement factor in all cases investigated indicates that the conformation of bound coenzyme is rather invariant in the different enzyme systems and overwhelmingly shifted toward an open form. Dissociation constants for epsilonNAD+-dehydrogenases complexes can be determined by monitoring the coenzyme fluorescence enhancement or the protein fluorescence quenching. In the case of yeast glyceraldehyde-3-phosphate dehydrogenase at pH 7.0 and t = 20 degrees the binding plots obtained by the two methods are coincident, and show no cooperativity. The affinity of epsilonNAD+ is generally lower than that of NAD+, although epsilonNAD+ maintains most of the binding characteristics of NAD+. For example, it forms a tight complex with horse liver alcohol dehydrogenase and pyrazole, and with octopine dehydrogenase saturated by L-arginine and pyruvate. One major difference in the binding behavior of NAD+ and epsilonNAD+ seems to be present in the muscle glyceraldehyde-3-phosphate dehydrogenase. In fact, no difference was found for epsilon NAD+ between the affinities of the third and fourth binding sites. The results and implications of this work are compared with those obtained recently by other authors.", "contents": "Relationship between fluorescence and conformation of epsilonNAD+ bound to dehydrogenases. This work reports on the interaction of the fluorescent nicotinamide 1,N6-ethenoadenine dinucleotide (epsilonNAD+) with horse liver alcohol dehydrogenase, octopine dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase from different sources (yeast, lobster muscle, and rabbit muscle). The coenzyme fluorescence is enhanced by a factor of 10-13 in all systems investigated. It is shown that this enhancement cannot be due to changes in the polarity of the environment upon binding, and that it must be rather ascribed to structural properties of the bound coenzyme. Although dynamic factors could also be important for inducing changes in the quantum yield of epsilonNAD+ fluorescence, the close similarity of the fluorescence enhancement factor in all cases investigated indicates that the conformation of bound coenzyme is rather invariant in the different enzyme systems and overwhelmingly shifted toward an open form. Dissociation constants for epsilonNAD+-dehydrogenases complexes can be determined by monitoring the coenzyme fluorescence enhancement or the protein fluorescence quenching. In the case of yeast glyceraldehyde-3-phosphate dehydrogenase at pH 7.0 and t = 20 degrees the binding plots obtained by the two methods are coincident, and show no cooperativity. The affinity of epsilonNAD+ is generally lower than that of NAD+, although epsilonNAD+ maintains most of the binding characteristics of NAD+. For example, it forms a tight complex with horse liver alcohol dehydrogenase and pyrazole, and with octopine dehydrogenase saturated by L-arginine and pyruvate. One major difference in the binding behavior of NAD+ and epsilonNAD+ seems to be present in the muscle glyceraldehyde-3-phosphate dehydrogenase. In fact, no difference was found for epsilon NAD+ between the affinities of the third and fourth binding sites. The results and implications of this work are compared with those obtained recently by other authors."} {"id": "PMID:164205", "title": "Conformational and functional studies of chemically modified cytochromes: N-bromosuccinimide- and formyl-cytochromes c.", "content": "N-bromosuccinimide-cytochromes c (Myer, Y. P. (1972), Biochemistry 11, 4195) and formyl-cytochrome c (Aviram, I and Schejter, A. (1971), Biochim. Biophys. Acta 229, 113) have been chromatographically purified, and the resulting components have been characterized in terms of their structure, conformation, and function. The activity measurements are considered in terms of the oxidizability, as the transference of an electron to solubilized cytochrome c oxidase, and reducibility, as the tendency to accept an electron from NADH-cytochrome c reductase. Conformational characterization has been carried out by absorption measurements, pH-spectroscopic behavior, circular dichroism, thermal denaturation, ionization of phenolic hydroxyls, the tendency to form the CO complex, and autoxidation with molecular oxygen. NBS-cytochrome c yields two major components, the relative proportions of which, with increasing modification of the protein, exhibit a pattern typical of the formation of the two in a consecutive manner. The first product contains the modification of the Trp-59 and Met-65 side chains, and the second contains the added modification of Met-80. The former in both valence states of iron is more or less like the native protein, except for an apparently slightly loosened heme crevice; the latter, as in other modifications involving modification of centrally coordinated Met-80, was found to be in a conformational state characteristic of the native protein with a disrupted central coordination complex, a loosened heme crevice, and small, but finite derangement of the polypeptide conformation. Functionally, the first component reflected 55% of the reducibility property and an unimpaired oxidizability property, while the latter exhibited derangement of both aspects of cytochrome c activity. Formyl-cytochrome c yielded a single component with modification of Trp-59. Conformationally, in both valence states, it is a molecular form with a disrupted central coordination complex, a loosened heme crevice, and gross derangement of the overall protein conformation. It exhibits a minimal reducibility property, 12%, whereas it retains a native-like tendency to transfer an electron to cytochrome c oxidase. The data from the NBS-cytochrome c components are analyzed with reference to the two forms in the earlier studies of the unpurified preparations. The results are found to be in agreement with one another. The selectivity between the reducibility and the oxidizability exhibited by the first NBS component and formyl-cytochrome c, irrespective of significant differences in the conformational and coordinational configurations of the two, has been viewed in light of a two-path, two-function model for oxidoreduction, as well as with reference to conformational and structural requirements for the oxidizability and reducibility properties of the molecule.", "contents": "Conformational and functional studies of chemically modified cytochromes: N-bromosuccinimide- and formyl-cytochromes c. N-bromosuccinimide-cytochromes c (Myer, Y. P. (1972), Biochemistry 11, 4195) and formyl-cytochrome c (Aviram, I and Schejter, A. (1971), Biochim. Biophys. Acta 229, 113) have been chromatographically purified, and the resulting components have been characterized in terms of their structure, conformation, and function. The activity measurements are considered in terms of the oxidizability, as the transference of an electron to solubilized cytochrome c oxidase, and reducibility, as the tendency to accept an electron from NADH-cytochrome c reductase. Conformational characterization has been carried out by absorption measurements, pH-spectroscopic behavior, circular dichroism, thermal denaturation, ionization of phenolic hydroxyls, the tendency to form the CO complex, and autoxidation with molecular oxygen. NBS-cytochrome c yields two major components, the relative proportions of which, with increasing modification of the protein, exhibit a pattern typical of the formation of the two in a consecutive manner. The first product contains the modification of the Trp-59 and Met-65 side chains, and the second contains the added modification of Met-80. The former in both valence states of iron is more or less like the native protein, except for an apparently slightly loosened heme crevice; the latter, as in other modifications involving modification of centrally coordinated Met-80, was found to be in a conformational state characteristic of the native protein with a disrupted central coordination complex, a loosened heme crevice, and small, but finite derangement of the polypeptide conformation. Functionally, the first component reflected 55% of the reducibility property and an unimpaired oxidizability property, while the latter exhibited derangement of both aspects of cytochrome c activity. Formyl-cytochrome c yielded a single component with modification of Trp-59. Conformationally, in both valence states, it is a molecular form with a disrupted central coordination complex, a loosened heme crevice, and gross derangement of the overall protein conformation. It exhibits a minimal reducibility property, 12%, whereas it retains a native-like tendency to transfer an electron to cytochrome c oxidase. The data from the NBS-cytochrome c components are analyzed with reference to the two forms in the earlier studies of the unpurified preparations. The results are found to be in agreement with one another. The selectivity between the reducibility and the oxidizability exhibited by the first NBS component and formyl-cytochrome c, irrespective of significant differences in the conformational and coordinational configurations of the two, has been viewed in light of a two-path, two-function model for oxidoreduction, as well as with reference to conformational and structural requirements for the oxidizability and reducibility properties of the molecule."} {"id": "PMID:164206", "title": "Metabolic properties of substrate-attached glycoproteins from normal and virus-transformed cells.", "content": "Balb/c 3T3, SV40-transformed 3T3 (SVT2), and Con A revertant variants of transformed cells leave a layer of glycoprotein on the culture substrate upon EGTA mediated removal of cells. The metabolic properties of this substrate-attached material (glycoprotein) have been examined. Pulse and cumulative radiolabeling experiments with glucosamine and leucine precursors established that this substrate-attached material accumulates on the substrate in growing cultures until cells have completely covered the substrate. The synthesis and/or deposition of the material diminished dramatically in cultures whose substrates had been completely covered with cells as observed microscopically, even though the contact-inhibited cell lines continued to make cell-associated and medium-secreted glycoproteins and transformed cells continued to divide and form multilayered cultures. Pulse-chase analysis using long periods of pulsing with radioactive leucine demonstrated that these glycoproteins are deposited directly on the substrate by cells and not subsequent to secretion into the medium. The substrate-attached material accumulated during long pulses was stably adherent to the substrate and displayed little appreciable turnover during 3 days of chasing of either sparse or dense cultures. Short-term pulse-chase analysis with leucine revealed two metabolically different pools of material-one which turns over very rapidly with a half-life of 2-3 hr (observed in both low-density and high-density cultures) and a second pool which is stably deposited on the substrate and whose proportion increased with the length of the radiolabeling period. No appreciable differences in the metabolic properties of substrate-attached material were observed in the three cell types studied during growth on a plastic substrate. These results are discussed with regard to the implicated roles of these glycoproteins in in mediating adhesion of normal and virus-transformed cells to the substrate.", "contents": "Metabolic properties of substrate-attached glycoproteins from normal and virus-transformed cells. Balb/c 3T3, SV40-transformed 3T3 (SVT2), and Con A revertant variants of transformed cells leave a layer of glycoprotein on the culture substrate upon EGTA mediated removal of cells. The metabolic properties of this substrate-attached material (glycoprotein) have been examined. Pulse and cumulative radiolabeling experiments with glucosamine and leucine precursors established that this substrate-attached material accumulates on the substrate in growing cultures until cells have completely covered the substrate. The synthesis and/or deposition of the material diminished dramatically in cultures whose substrates had been completely covered with cells as observed microscopically, even though the contact-inhibited cell lines continued to make cell-associated and medium-secreted glycoproteins and transformed cells continued to divide and form multilayered cultures. Pulse-chase analysis using long periods of pulsing with radioactive leucine demonstrated that these glycoproteins are deposited directly on the substrate by cells and not subsequent to secretion into the medium. The substrate-attached material accumulated during long pulses was stably adherent to the substrate and displayed little appreciable turnover during 3 days of chasing of either sparse or dense cultures. Short-term pulse-chase analysis with leucine revealed two metabolically different pools of material-one which turns over very rapidly with a half-life of 2-3 hr (observed in both low-density and high-density cultures) and a second pool which is stably deposited on the substrate and whose proportion increased with the length of the radiolabeling period. No appreciable differences in the metabolic properties of substrate-attached material were observed in the three cell types studied during growth on a plastic substrate. These results are discussed with regard to the implicated roles of these glycoproteins in in mediating adhesion of normal and virus-transformed cells to the substrate."} {"id": "PMID:164207", "title": "Synthesis P1-dolichyl P2-alpha-D-mannopyranosyl pyrophosphate. The acid and alkaline hydrolysis of polyisoprenyl alpha-D-mannopyranosyl mono- and pyrophosphate diesters.", "content": "P1-Dolichyl P2-ALPHA-D-mannopyranosyl pyrophosphate (9) has been chemically synthesized by a method developed for the corresponding citronellyl derivative, which also contains a saturated alpha isoprene residue. In each case, the P1-polyisoprenyl P2-diphenyl pyrophosphate was treated with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate to give a fully acetylated pyrophosphate diester, which was purified chromatographically and subsequently deacetylated. The citronellyl and dolichyl pyrophosphate diesters were compared with the previously synthesized citronellyl and dolichyl alpha-D-mannopyranosyl phosphate, respectively, by chromatography and by hydrolysis experiments. Good separations of the monophosphate from the corresponding pyrophosphate were achieved by silica gel tlc in a variety of solvent systems. Brief dilute acid hydrolysis of both the mono- and pyrophosphate diesters gave D-mannose and no alpha-D-mannosyl phosphate, the other products being polyprenyl phosphate and pyrophosphate, respectively. When the polyprenyl alpha-D-mannopyranosyl mono- and pyrophosphate diesters were treated with hot dilute alkali, the major products were polyprenyl phosphate and substances arising from the breakdown of D-mannose, indicating that the alpha-D-mannosyl phosphate bond was the most labile linkage in both compounds. However, the formation of a small proportion of free dolichol indicated that alpha-D-mannosyl phosphate was also formed to a minor extent. The interpretation of the results of the alkaline hydrolysis was complicated by the instability of D-mannose under basic conditions, it being almost completely degraded by even a brief treatment.", "contents": "Synthesis P1-dolichyl P2-alpha-D-mannopyranosyl pyrophosphate. The acid and alkaline hydrolysis of polyisoprenyl alpha-D-mannopyranosyl mono- and pyrophosphate diesters. P1-Dolichyl P2-ALPHA-D-mannopyranosyl pyrophosphate (9) has been chemically synthesized by a method developed for the corresponding citronellyl derivative, which also contains a saturated alpha isoprene residue. In each case, the P1-polyisoprenyl P2-diphenyl pyrophosphate was treated with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate to give a fully acetylated pyrophosphate diester, which was purified chromatographically and subsequently deacetylated. The citronellyl and dolichyl pyrophosphate diesters were compared with the previously synthesized citronellyl and dolichyl alpha-D-mannopyranosyl phosphate, respectively, by chromatography and by hydrolysis experiments. Good separations of the monophosphate from the corresponding pyrophosphate were achieved by silica gel tlc in a variety of solvent systems. Brief dilute acid hydrolysis of both the mono- and pyrophosphate diesters gave D-mannose and no alpha-D-mannosyl phosphate, the other products being polyprenyl phosphate and pyrophosphate, respectively. When the polyprenyl alpha-D-mannopyranosyl mono- and pyrophosphate diesters were treated with hot dilute alkali, the major products were polyprenyl phosphate and substances arising from the breakdown of D-mannose, indicating that the alpha-D-mannosyl phosphate bond was the most labile linkage in both compounds. However, the formation of a small proportion of free dolichol indicated that alpha-D-mannosyl phosphate was also formed to a minor extent. The interpretation of the results of the alkaline hydrolysis was complicated by the instability of D-mannose under basic conditions, it being almost completely degraded by even a brief treatment."} {"id": "PMID:164208", "title": "Glucocorticoid receptors in mouse mammary tumors: Specific binding to nuclear components.", "content": "The specific interaction of glucocorticoids with nuclei of mouse mammary tumor was studied in vitro by incubation of the tissue with [3H]dexamethasone at 25 degrees. It was demonstrated that the mammary tumors contain a limited number of specific nuclear binding sites which were saturated with low hormone concentrations (10-8 M)9 The concentrations of specific binding sites in the nuclei were related to the concentration of cytoplasmic binding sites of unincubated tissues and varied between individual tumors. The binding component in the nuclei appeared to be a protein and was easily solubilized with 0.4 M KCl containing buffers. The ability of various corticoids to block the nuclear localization of the steroid correlated well with their glucocorticoid potency. Estradiol and progesterone at concentrations of 10-6 M were also effective in competing for the glucocorticoid receptor binding sites. However, while the glucocorticoids such as hydrocortisone and corticosterone translocated to nuclear sites also specific for dexamethasone, estradiol and progesterone competed for the cytoplasmic binding sites and did not translocate to the nucleus. The possible significance of the interaction of various steroids with the glucocorticoid receptors in mammary tumors is discussed.", "contents": "Glucocorticoid receptors in mouse mammary tumors: Specific binding to nuclear components. The specific interaction of glucocorticoids with nuclei of mouse mammary tumor was studied in vitro by incubation of the tissue with [3H]dexamethasone at 25 degrees. It was demonstrated that the mammary tumors contain a limited number of specific nuclear binding sites which were saturated with low hormone concentrations (10-8 M)9 The concentrations of specific binding sites in the nuclei were related to the concentration of cytoplasmic binding sites of unincubated tissues and varied between individual tumors. The binding component in the nuclei appeared to be a protein and was easily solubilized with 0.4 M KCl containing buffers. The ability of various corticoids to block the nuclear localization of the steroid correlated well with their glucocorticoid potency. Estradiol and progesterone at concentrations of 10-6 M were also effective in competing for the glucocorticoid receptor binding sites. However, while the glucocorticoids such as hydrocortisone and corticosterone translocated to nuclear sites also specific for dexamethasone, estradiol and progesterone competed for the cytoplasmic binding sites and did not translocate to the nucleus. The possible significance of the interaction of various steroids with the glucocorticoid receptors in mammary tumors is discussed."} {"id": "PMID:164209", "title": "An investigation of the role of the copper in galactose oxidase.", "content": "Galactose oxidase is a metalloenzyme containing a single copper atom per molecule. The mechanism of action of galactose oxidase is studied in this paper by investigating substrate specificity and activation by peroxidase, and probing the copper site by electron spin resonance (ESR) spectroscopy. Line-shape simulation of ESR spectra are also reported and a comparison is made between observed and simulated spectra for galactose oxidase. A comparison is also reported for the enzyme from various commercial sources and enzyme isolated from a fungus in this laboratory. The results of this investigation suggest that the copper is in an environment of four in-plane nitrogens with axial symmetry.", "contents": "An investigation of the role of the copper in galactose oxidase. Galactose oxidase is a metalloenzyme containing a single copper atom per molecule. The mechanism of action of galactose oxidase is studied in this paper by investigating substrate specificity and activation by peroxidase, and probing the copper site by electron spin resonance (ESR) spectroscopy. Line-shape simulation of ESR spectra are also reported and a comparison is made between observed and simulated spectra for galactose oxidase. A comparison is also reported for the enzyme from various commercial sources and enzyme isolated from a fungus in this laboratory. The results of this investigation suggest that the copper is in an environment of four in-plane nitrogens with axial symmetry."} {"id": "PMID:164210", "title": "Mandelate racemase from Pseudomonas putida. Magnetic resonance and kinetic studies of the mechanism of catalysis.", "content": "The interactions of mandelate racemase with divalent metal ion, substrate, and competitive inhibitors were investigated. The enzyme was found by electron paramagnetic resonance (EPR) to bind 0.9 Mn2+ ion per subunit with a dissociation constant of 8 muM, in agreement with its kinetically determined activator constant. Also, six additional Mn2+ ions were found to bind to the enzyme, much more weakly, with a dissociation constant of 1.5 mM. Binding to the enzyme at the tight site enhances the effect of Mn2+ on the longitudinal relaxation rate (1/T1p) of water protons by a factor of 11.9 at 24.3 MHz. From the frequency dependence of 1/T1p, it was determined that there are similar to 3 water ligands on enzyme-bound Mn2+ which exchange at a rate larger than or equal to 10-7 sec-1. The correlation time for enzyme-bound Mn2+-water interaction is frequency-dependent, indicating it to be dominated by the electron spin relaxation time of Mn2+. Formation of the ternary enzyme-Mn2+-mandelate complex decreases the number of fast exchanging water ligands by similar to 1, but does not affect tau-c, suggesting the displacement or occlusion of a water ligand. The competitive inhibitors D,L-alpha-phenylglycerate and salicylate produce little or no change in the enzyme-Mn2+-H2O interaction, but ternary complexes are detected indirectly by changes in the dissociation constant of the enzyme-Mn2+ complex and by mutual competition experiments. In all cases the dissociation constants of substrates and competitive inhibitors from ternary complexes determined by magnetic resonance titrations agree with K-M and K-i values determined kinetically and therefore reflect kinetically active complexes. From the paramagnetic effects of Mn2+ on 1/T1 and 1/T2 of the 13C-enriched carbons of 1-[13C]-D,L-mandelate and 2-[13C]-D,L-mandelate, Mn2+ to carboxylate carbon and Mn2+ to carbinol carbon distances of 2.93 plus or minus 0.04 and 2.71 plus or minus 0.04 A, respectively, were calculated, indicating bidentate chelation in the binary Mn2+-mandelate complex. In the active ternary complex of enzyme, Mn2+, and D,L-mandelate, these distances increase to 5.5 plus or minus 0.2 and 7.2 plus or minus 0.2 A, respectively, indicating the presence of at least 98.9% of a second sphere complex in which Mn2+, and C1 and C2 carbon atoms are in a linear array. The water relaxation data suggest that a water ligand is immobilized between the enzyme-bound Mn2+ and the carboxylate of the bound substrate. This intervening water ligand may polarize or protonate the carboxyl group. From 1/T2p the rate of dissociation of the substrate from this ternary complex (larger than or equal to 5.6 times 10-4 sec-1) is at least 52 times greater than the maximal turnover number of the enzyme (1070 sec-1), indicating that the complex detected by nuclear magnetic resonance (NMR) is kinetically competent to participate in catalysis. Relationships among the microscopic rate constants are considered.", "contents": "Mandelate racemase from Pseudomonas putida. Magnetic resonance and kinetic studies of the mechanism of catalysis. The interactions of mandelate racemase with divalent metal ion, substrate, and competitive inhibitors were investigated. The enzyme was found by electron paramagnetic resonance (EPR) to bind 0.9 Mn2+ ion per subunit with a dissociation constant of 8 muM, in agreement with its kinetically determined activator constant. Also, six additional Mn2+ ions were found to bind to the enzyme, much more weakly, with a dissociation constant of 1.5 mM. Binding to the enzyme at the tight site enhances the effect of Mn2+ on the longitudinal relaxation rate (1/T1p) of water protons by a factor of 11.9 at 24.3 MHz. From the frequency dependence of 1/T1p, it was determined that there are similar to 3 water ligands on enzyme-bound Mn2+ which exchange at a rate larger than or equal to 10-7 sec-1. The correlation time for enzyme-bound Mn2+-water interaction is frequency-dependent, indicating it to be dominated by the electron spin relaxation time of Mn2+. Formation of the ternary enzyme-Mn2+-mandelate complex decreases the number of fast exchanging water ligands by similar to 1, but does not affect tau-c, suggesting the displacement or occlusion of a water ligand. The competitive inhibitors D,L-alpha-phenylglycerate and salicylate produce little or no change in the enzyme-Mn2+-H2O interaction, but ternary complexes are detected indirectly by changes in the dissociation constant of the enzyme-Mn2+ complex and by mutual competition experiments. In all cases the dissociation constants of substrates and competitive inhibitors from ternary complexes determined by magnetic resonance titrations agree with K-M and K-i values determined kinetically and therefore reflect kinetically active complexes. From the paramagnetic effects of Mn2+ on 1/T1 and 1/T2 of the 13C-enriched carbons of 1-[13C]-D,L-mandelate and 2-[13C]-D,L-mandelate, Mn2+ to carboxylate carbon and Mn2+ to carbinol carbon distances of 2.93 plus or minus 0.04 and 2.71 plus or minus 0.04 A, respectively, were calculated, indicating bidentate chelation in the binary Mn2+-mandelate complex. In the active ternary complex of enzyme, Mn2+, and D,L-mandelate, these distances increase to 5.5 plus or minus 0.2 and 7.2 plus or minus 0.2 A, respectively, indicating the presence of at least 98.9% of a second sphere complex in which Mn2+, and C1 and C2 carbon atoms are in a linear array. The water relaxation data suggest that a water ligand is immobilized between the enzyme-bound Mn2+ and the carboxylate of the bound substrate. This intervening water ligand may polarize or protonate the carboxyl group. From 1/T2p the rate of dissociation of the substrate from this ternary complex (larger than or equal to 5.6 times 10-4 sec-1) is at least 52 times greater than the maximal turnover number of the enzyme (1070 sec-1), indicating that the complex detected by nuclear magnetic resonance (NMR) is kinetically competent to participate in catalysis. Relationships among the microscopic rate constants are considered."} {"id": "PMID:164211", "title": "Effect of salts and polyamines on T4 polynucleotide kinase.", "content": "The activity of T4 polynucleotide kinase (EC 2.7.1.78) was found to be greatly stimulated by salts, such as NaCl and KCl, and polyamines such as spermine and spermidine. Up to a sixfold increase in initial rates was observed with a variety of different single-stranded DNAs and mono- and oligonucleotides. The optimal concentrations of salts were 0.125 M, corresponding to a total ionic strength of mu equals 0.19. For polyamines the optimal concentrations were found to be at approximately 2 mM. With low enzyme concentration and in the absence of activators complete phosphorylation was not achieved for a number of substrates. In the presence of salts or polyamines or high concentration of enzyme the phosphorylation proceeded to completion. Addition of salt led to an increase in both the apparent V-max and the Michaelis constant for the DNA substrate whereas the Michaelis constant of ATP remained unchanged. Polyamines had a similar influence on the kinetic constants for the DNA substrate whereas a decrease was found for the apparent Michaelis constant for ATP. The overall mechanism in the presence of activators was found to be sequential but probably of a rapid equilibrium random type. Of the inorganic anions tested both P-i and PP-i inhibited the enzyme in a competitive manner with both substrates.", "contents": "Effect of salts and polyamines on T4 polynucleotide kinase. The activity of T4 polynucleotide kinase (EC 2.7.1.78) was found to be greatly stimulated by salts, such as NaCl and KCl, and polyamines such as spermine and spermidine. Up to a sixfold increase in initial rates was observed with a variety of different single-stranded DNAs and mono- and oligonucleotides. The optimal concentrations of salts were 0.125 M, corresponding to a total ionic strength of mu equals 0.19. For polyamines the optimal concentrations were found to be at approximately 2 mM. With low enzyme concentration and in the absence of activators complete phosphorylation was not achieved for a number of substrates. In the presence of salts or polyamines or high concentration of enzyme the phosphorylation proceeded to completion. Addition of salt led to an increase in both the apparent V-max and the Michaelis constant for the DNA substrate whereas the Michaelis constant of ATP remained unchanged. Polyamines had a similar influence on the kinetic constants for the DNA substrate whereas a decrease was found for the apparent Michaelis constant for ATP. The overall mechanism in the presence of activators was found to be sequential but probably of a rapid equilibrium random type. Of the inorganic anions tested both P-i and PP-i inhibited the enzyme in a competitive manner with both substrates."} {"id": "PMID:164212", "title": "Binding of manganese(II) to DNA and the competitive effects of metal ions and organic cations. An electron paramagnetic resonance study.", "content": "The binding of manganese(II) to DNA was studied by monitoring the concentration of free Mn2+ by electron paramagnetic resonance (EPR). It was found that the association constnat of the Mn-DNA complex depends upon the degree of saturation. The competitive effects of magnesium, calcium, sodium, and a number of organic cations including the antibiotic drug daunomycin were analyzed and the parameters describing the cation-DNA interaction were evaluated. It was found that the association constant as well as the parameter describing its dependence upon the degree of saturation decrease along the series Mn, Mg, Ca, Na. Differences in the extent of interaction with the base nitrogens (N-7) are suggested as the possible mechanisms leading to these observations. The EPR spectrum of the manganese-DNA complex was found to be similar to that of manganese-nucleotide complexes suggesting a similar mode of coordination. A comparison of the results of competitive and direct binding studies reveals some salient features of the small molecule-DNA interaction and leads to the conclusion that manganese binds at the major groove of the DNA helix.", "contents": "Binding of manganese(II) to DNA and the competitive effects of metal ions and organic cations. An electron paramagnetic resonance study. The binding of manganese(II) to DNA was studied by monitoring the concentration of free Mn2+ by electron paramagnetic resonance (EPR). It was found that the association constnat of the Mn-DNA complex depends upon the degree of saturation. The competitive effects of magnesium, calcium, sodium, and a number of organic cations including the antibiotic drug daunomycin were analyzed and the parameters describing the cation-DNA interaction were evaluated. It was found that the association constant as well as the parameter describing its dependence upon the degree of saturation decrease along the series Mn, Mg, Ca, Na. Differences in the extent of interaction with the base nitrogens (N-7) are suggested as the possible mechanisms leading to these observations. The EPR spectrum of the manganese-DNA complex was found to be similar to that of manganese-nucleotide complexes suggesting a similar mode of coordination. A comparison of the results of competitive and direct binding studies reveals some salient features of the small molecule-DNA interaction and leads to the conclusion that manganese binds at the major groove of the DNA helix."} {"id": "PMID:164213", "title": "Evidence for glucocorticoid transport into AtT-20/D-1 cells.", "content": "Glucocorticoid uptake by AtT-20/D-1 mouse pituitary adenocarcinoma cells grown in tissue culture was examined. The binding of triamcinolone acetonide, a potent synthetic glucocorticoid, by intact cells and by cell cytosol was studied at both 4 and 25 degrees. Specific binding of [3H]triamcinolone acetonide by intact cells was markedly different from cell-free cytosol binding at 4 degrees. Intact cells bound a relatively small amount of labeled steroid within 2 min, after which no further binding was observed. In contrast, the receptor in a cell-free cytosol preparation was capable of binding steroid progressively at 4 degrees, indicating that the limited binding by intact cells was not a consequence of receptor characteristics. At 25 degrees, uptake by intact cells and cytosol was nearly identical and appeared to be limited only by the binding kinetics of the cytosol receptor. Estradiol-17 beta, a nonglucocorticoid steroid, was not bound by the AtT-20/D-1 cell at 4 degrees. Triamcinolone was not bound significantly at 4 or 25 degrees by an adrenal carcinoma cell that does not appear to be a glucocorticoid target cell. An Arrhenius plot of cell steroid uptake vs. the reciprocal of absolute temperature revealed an abrupt change in slope at 16 degrees, which is compatible with the temperature-dependent mechanism involved in glucocortidoid uptake being associated with lipid constituents of the cell membrane. These data suggest that glucocorticoid uptake by this target cell involves a mechanism of specific, temperature-dependent transport through the cell membrane.", "contents": "Evidence for glucocorticoid transport into AtT-20/D-1 cells. Glucocorticoid uptake by AtT-20/D-1 mouse pituitary adenocarcinoma cells grown in tissue culture was examined. The binding of triamcinolone acetonide, a potent synthetic glucocorticoid, by intact cells and by cell cytosol was studied at both 4 and 25 degrees. Specific binding of [3H]triamcinolone acetonide by intact cells was markedly different from cell-free cytosol binding at 4 degrees. Intact cells bound a relatively small amount of labeled steroid within 2 min, after which no further binding was observed. In contrast, the receptor in a cell-free cytosol preparation was capable of binding steroid progressively at 4 degrees, indicating that the limited binding by intact cells was not a consequence of receptor characteristics. At 25 degrees, uptake by intact cells and cytosol was nearly identical and appeared to be limited only by the binding kinetics of the cytosol receptor. Estradiol-17 beta, a nonglucocorticoid steroid, was not bound by the AtT-20/D-1 cell at 4 degrees. Triamcinolone was not bound significantly at 4 or 25 degrees by an adrenal carcinoma cell that does not appear to be a glucocorticoid target cell. An Arrhenius plot of cell steroid uptake vs. the reciprocal of absolute temperature revealed an abrupt change in slope at 16 degrees, which is compatible with the temperature-dependent mechanism involved in glucocortidoid uptake being associated with lipid constituents of the cell membrane. These data suggest that glucocorticoid uptake by this target cell involves a mechanism of specific, temperature-dependent transport through the cell membrane."} {"id": "PMID:164214", "title": "Stimulus-secretion coupling in platelets. Effects of drugs on secretion on adenosine 5'-triphosphate.", "content": "The mechanism of stimulus-secretion coupling in platelets was investigated by observing the effects of drugs on the kinetics on ATP secretion induced by either thrombin or the divalent cation ionophore A23187. The actual secretion is the same with either of these agents, since the rate constants and activation energies of secretion are the same and since drugs that affect the final, enzyme-independent steps of thrombin-induced secretion have the same effect on ionophore-induced secretion. Drugs that affect early steps of thrombin-induced secretion have no effect on ionophore-induced secretion. Drugs that act through cAMP (PGE1, theophylline, dibutyryl-cAMP) slow an early step in the mechanism of thrombin-induced secretion and completely block at higher levels, with the required concentration of inhibitor dependent on thrombin concentration. The inhibition of rate appears to be all-or-none, with no intermediate rates observed. By replacing thrombin with trypsin, which makes it possible to observe a complete change in rate-determining step from an enzyme-dependent to an enzyme-independent platelet step, it was found that these drugs slow the rate only when the enzyme-independent step is rate determining. These drugs have no effect on A23187-induced secretion. It was concluded that cAMP inhibits at a step after the enzyme step but before the final step by interfering with transmission of the stimulus-secretion coupling signal. Disruption of microfilament function by cytochalasin B (10 muM) accelerates the rate of secretion induced by either thrombin or ionophore. The microtubule agents colchicine, vinblastine, and vincristine had effects only at concentrations above those usually considered necessary for the specific inhibition of microtubule function. Drugs that inhibit prostaglandin synthesis (aspirin, indomethacin, eicosatetraynoic acid), drugs that block ATP production (antimycin A, deoxyglucose), or several other drugs previously reported to inhibit platelet function had no effect on secretion.", "contents": "Stimulus-secretion coupling in platelets. Effects of drugs on secretion on adenosine 5'-triphosphate. The mechanism of stimulus-secretion coupling in platelets was investigated by observing the effects of drugs on the kinetics on ATP secretion induced by either thrombin or the divalent cation ionophore A23187. The actual secretion is the same with either of these agents, since the rate constants and activation energies of secretion are the same and since drugs that affect the final, enzyme-independent steps of thrombin-induced secretion have the same effect on ionophore-induced secretion. Drugs that affect early steps of thrombin-induced secretion have no effect on ionophore-induced secretion. Drugs that act through cAMP (PGE1, theophylline, dibutyryl-cAMP) slow an early step in the mechanism of thrombin-induced secretion and completely block at higher levels, with the required concentration of inhibitor dependent on thrombin concentration. The inhibition of rate appears to be all-or-none, with no intermediate rates observed. By replacing thrombin with trypsin, which makes it possible to observe a complete change in rate-determining step from an enzyme-dependent to an enzyme-independent platelet step, it was found that these drugs slow the rate only when the enzyme-independent step is rate determining. These drugs have no effect on A23187-induced secretion. It was concluded that cAMP inhibits at a step after the enzyme step but before the final step by interfering with transmission of the stimulus-secretion coupling signal. Disruption of microfilament function by cytochalasin B (10 muM) accelerates the rate of secretion induced by either thrombin or ionophore. The microtubule agents colchicine, vinblastine, and vincristine had effects only at concentrations above those usually considered necessary for the specific inhibition of microtubule function. Drugs that inhibit prostaglandin synthesis (aspirin, indomethacin, eicosatetraynoic acid), drugs that block ATP production (antimycin A, deoxyglucose), or several other drugs previously reported to inhibit platelet function had no effect on secretion."} {"id": "PMID:164215", "title": "The outer membrane of Proteus mirabilis. II. The extractable lipid fraction and electron-paramagnetic resonance analysis of the outer and cytoplasmic membranes.", "content": "1. The lipid fraction extracted from the outer and cytoplasmic membranes of Proteus mirabilis with chloroform/methanol consisted almost entirely of phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. 2. The phospholipid content of the cytoplasmic membrane was more than twice that of the outer membrane (38% as against 18% of the total dry weight) and the proportions of the three phospholipids differed somewhat in the two membranes. Yet, the fatty acid composition of the extractable lipids was essentially the same in both membranes. 3. The freedom of motion of spin-labeled fatty acids in the outer membrane of P. mirabilis depended markedly on temperature and on the position of the nitroxide group on the hydrocarbon chain of the probe, suggesting that the local environment of the probe is an associate lipid structure with the properties of a bilayer. Nevertheless, the mobility of the probe was more restricted in the outer membrane than in the cytoplasmic membrane, indicating a higher viscosity of the outer membrane. 4. Chloroform/methanol completely removed the phospholipids from the outer membrane, leaving the lipopolysaccharide moiety intact. The motion of spin-labeled fatty acids in the extracted membranes was, however, highly restricted, suggesting that, in the native outer membrane, the local environment of the probe is composed of phospholipids rather than lipopolysaccharide. Aqueous acetone extraction removed only 75-80% of the phospholipids of the outer membrane. Nevertheless, the mobility of the spin-labeled fatty acid remained highly restricted, suggesting the existence of two phospholipid environments in the outer membrane differing in the nature of their association with the lipopolysaccharide and protein moieties.", "contents": "The outer membrane of Proteus mirabilis. II. The extractable lipid fraction and electron-paramagnetic resonance analysis of the outer and cytoplasmic membranes. 1. The lipid fraction extracted from the outer and cytoplasmic membranes of Proteus mirabilis with chloroform/methanol consisted almost entirely of phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. 2. The phospholipid content of the cytoplasmic membrane was more than twice that of the outer membrane (38% as against 18% of the total dry weight) and the proportions of the three phospholipids differed somewhat in the two membranes. Yet, the fatty acid composition of the extractable lipids was essentially the same in both membranes. 3. The freedom of motion of spin-labeled fatty acids in the outer membrane of P. mirabilis depended markedly on temperature and on the position of the nitroxide group on the hydrocarbon chain of the probe, suggesting that the local environment of the probe is an associate lipid structure with the properties of a bilayer. Nevertheless, the mobility of the probe was more restricted in the outer membrane than in the cytoplasmic membrane, indicating a higher viscosity of the outer membrane. 4. Chloroform/methanol completely removed the phospholipids from the outer membrane, leaving the lipopolysaccharide moiety intact. The motion of spin-labeled fatty acids in the extracted membranes was, however, highly restricted, suggesting that, in the native outer membrane, the local environment of the probe is composed of phospholipids rather than lipopolysaccharide. Aqueous acetone extraction removed only 75-80% of the phospholipids of the outer membrane. Nevertheless, the mobility of the spin-labeled fatty acid remained highly restricted, suggesting the existence of two phospholipid environments in the outer membrane differing in the nature of their association with the lipopolysaccharide and protein moieties."} {"id": "PMID:164216", "title": "The biogenesis of mitochondrial membranes in the yeast Saccharomyces cerevisiae.", "content": "Membrane lipids of yeast mitochondria have been enriched by growing yeast cells in minimal medium supplemented with specific unsaturated fatty acids as the sole lipid supplement. Using the activity of marker enzymes for the outer (kynurenine hydroxylase) and inner (cytochrome c oxidase and oligomycin-sensitive ATPase) mitochondrial membranes, Arrhenius plots have been constructed using both promitochondria and mitochondria obtained from O2-adapting cells in the presence of a second unsaturated fatty acid (i.e. linoleate (N2) to elaidic (O2)). Transition temperatures which reflect the unsaturated fatty acid enrichment of the new membranes reveal interesting features involved in the mechanism of the assembly of these two mitochondrial membranes. This approach was further enforced with both lipid depletion and mitochondrial protein inhibition studies. Kynurenine hydroxylase which does not require fatty acid for its continued synthesis during aerobiosis seems to be incorporated into the preformed linoleate-anaerobic outer membrane. The newly synthesized activities of inner mitochondrial membrane enzymes on the other hand, appear to integrate their activity into newly formed aerobic-elaidic-rich inner membrane. These latter enzymes show a distinct dependence on fatty acid supplement for their continued synthesis during their aerobic phase. This suggests that O2-dependent proteo-lipid precursors are formed before these enzymes are integrated into their membrane mosaic. Two separate models are proposed to explain these results, one for the lipid-rich outer mitochondrial membrane and another for the protein-rich inner mitochondrial membrane.", "contents": "The biogenesis of mitochondrial membranes in the yeast Saccharomyces cerevisiae. Membrane lipids of yeast mitochondria have been enriched by growing yeast cells in minimal medium supplemented with specific unsaturated fatty acids as the sole lipid supplement. Using the activity of marker enzymes for the outer (kynurenine hydroxylase) and inner (cytochrome c oxidase and oligomycin-sensitive ATPase) mitochondrial membranes, Arrhenius plots have been constructed using both promitochondria and mitochondria obtained from O2-adapting cells in the presence of a second unsaturated fatty acid (i.e. linoleate (N2) to elaidic (O2)). Transition temperatures which reflect the unsaturated fatty acid enrichment of the new membranes reveal interesting features involved in the mechanism of the assembly of these two mitochondrial membranes. This approach was further enforced with both lipid depletion and mitochondrial protein inhibition studies. Kynurenine hydroxylase which does not require fatty acid for its continued synthesis during aerobiosis seems to be incorporated into the preformed linoleate-anaerobic outer membrane. The newly synthesized activities of inner mitochondrial membrane enzymes on the other hand, appear to integrate their activity into newly formed aerobic-elaidic-rich inner membrane. These latter enzymes show a distinct dependence on fatty acid supplement for their continued synthesis during their aerobic phase. This suggests that O2-dependent proteo-lipid precursors are formed before these enzymes are integrated into their membrane mosaic. Two separate models are proposed to explain these results, one for the lipid-rich outer mitochondrial membrane and another for the protein-rich inner mitochondrial membrane."} {"id": "PMID:164217", "title": "Kinetics of glycerol uptake by the perfused rat liver. Membrane transport, phosphorylation and effect on NAD redox level.", "content": "The kinetics of glycerol uptake by the perfused rat liver were determined according to a model which includes membrane transport, intracellular phosphorylation and competitive inhibition of glycerol phosphorylation by L-glycerol 3-phosphate. The membrane transport obeys first-order kinetics at concentrations below 10 mM in the affluent medium. The K-m of the glycerol phosphorylation was 10 muM and the K-i of the L-glycerol 3-phosphate inhibition was 50 muM. The maximum activity (V) was 3.70 mumoles/min per g liver wet wt. These results are similar to in vitro kinetics of the glycerol kinase, except that K-i was found to be somewhat lower in the intact organ. At low glycerol concentrations, a steep concentration gradient exists across the liver cell membrane. The increase in the lactate to pyruvate concentration ratio during glycerol metabolism is related to the actual concentration of L-glycerol 3-phosphate, not to the rate of glycerol uptake.", "contents": "Kinetics of glycerol uptake by the perfused rat liver. Membrane transport, phosphorylation and effect on NAD redox level. The kinetics of glycerol uptake by the perfused rat liver were determined according to a model which includes membrane transport, intracellular phosphorylation and competitive inhibition of glycerol phosphorylation by L-glycerol 3-phosphate. The membrane transport obeys first-order kinetics at concentrations below 10 mM in the affluent medium. The K-m of the glycerol phosphorylation was 10 muM and the K-i of the L-glycerol 3-phosphate inhibition was 50 muM. The maximum activity (V) was 3.70 mumoles/min per g liver wet wt. These results are similar to in vitro kinetics of the glycerol kinase, except that K-i was found to be somewhat lower in the intact organ. At low glycerol concentrations, a steep concentration gradient exists across the liver cell membrane. The increase in the lactate to pyruvate concentration ratio during glycerol metabolism is related to the actual concentration of L-glycerol 3-phosphate, not to the rate of glycerol uptake."} {"id": "PMID:164218", "title": "Binding of Au(CN)2- and Pt(CN)4-2- to horse liver alcohol dehydrogenase. A 35C1NMR relaxation study.", "content": "The binding of Au(CN)2- and Pt(CN)4-2- ions to the coenzyme binding site of horse liver alcohol dehydrogenase (alcohol : NAD+ oxidoreductase EC 1.1.1.1) has been studied by 35C1 nuclear magnetic relaxation. Longitudinal relaxation rates were analyzed in terms of a simple model and binding constants for Au(CN)2-, Pt(CN)4-2- and C1- were estimated. From a comparison between transverse and longitudinal relaxation rates the correlation time and the quadrupole coupling constant of bound chloride ion were obtained. The quadrupole coupling constant estimated from a simple electrostatic model for chloride ion interacting with an arginine group agrees with the experimental value.", "contents": "Binding of Au(CN)2- and Pt(CN)4-2- to horse liver alcohol dehydrogenase. A 35C1NMR relaxation study. The binding of Au(CN)2- and Pt(CN)4-2- ions to the coenzyme binding site of horse liver alcohol dehydrogenase (alcohol : NAD+ oxidoreductase EC 1.1.1.1) has been studied by 35C1 nuclear magnetic relaxation. Longitudinal relaxation rates were analyzed in terms of a simple model and binding constants for Au(CN)2-, Pt(CN)4-2- and C1- were estimated. From a comparison between transverse and longitudinal relaxation rates the correlation time and the quadrupole coupling constant of bound chloride ion were obtained. The quadrupole coupling constant estimated from a simple electrostatic model for chloride ion interacting with an arginine group agrees with the experimental value."} {"id": "PMID:164219", "title": "Cyclic 3',5'-AMP phosphodiesterase of rabbit aorta.", "content": "Cyclic AMP and cyclic GMP phosphodiesterase activities (3' : 5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) were demonstrated in the isolated intima, media, and adventitia of rabbit aorta. The activity for cyclic AMP hydrolysis in the intima was 2.7-fold higher than that for cyclic GMP hydrolysis. The activity for cyclic AMP hydrolysis in the media was approximately equal to that for cyclic GMP hydrolysis, but in the adventitia, cyclic GMP hydrolytic activity was 2.1-fold higher than cyclic AMP hydrolytic activity. Distribution of the activator of the phosphodiesterase was studied in the three layers. Each layer contained the activator. The activator was predominantly localized in the smooth muscle layer (the media). The effect of the activator and Ca2+ on the media cyclic AMP and cyclic GMP phosphodiesterase was also briefly studied. The activity of the cyclic GMP phosphodiesterase was stimulated by micromolar concentration of Ca2+ in the presence of the activator. However, the activity of the cyclic AMP phosphodiesterase was not significantly stimulated by Ca2+ up to 100 muM in the presence of the activator. Above 90% of cyclic nucleotide phosphodiesterase activity in the whole aorta was found to be derived from the media. A major portion (60-70%) of the media enzyme was found in 105 000 times g supernatant. Cyclic AMP phosphodiesterase in the supernatant was partially purified through Sepharose 6B column chromatography and partially separated from cyclic GMP phosphodiesterase. Using a partially purified preparation from the 105 000 times g supernatant the main kinetic parameters were specified as follows: 1) The pH optimum was found to be about 9.0 using Tris-maleate buffer. The maximum stimulation of the enzyme by Mg2+ was achieved at 4mM of MgC12. 2) High concentration of cyclic GMP (0.1 mM) inhibited noncompetitively the enzyme activity, and the activity was not stimulated at any tested concentration of cyclic GMP. 3) Activity-substrate concentration relationship revealed a high affinity (Km equals 1.0 muM) and low affinity (Km equals 45 muM) for cyclic AMP. The homogenate and 105 000 times g supernatant of the media also showed non-linear kinetics similar to the Sepharose 6B preparation and their apparent Km values for cyclic AMP hydrolysis were 1.2 muM and 36-40 muM and an enzyme extracted by sonication from 105 000 times g precipitate also exhibited non-linear kinetics (Km equals 5.1 muM and 70 muM). 4) Papaverine exhibited much stronger inhibition on the aorta cyclic AMP phosphodiesterase (50% inhibition of the intima enzyme, I5 o at 0.62 muM, I5 o of the media at 0.62 muM and I5 o of the adventitia at 1.0 muM) than on the brain (I5 o at 8.5 muM) and serum (I5 o at 20 muM) cyclic AMP phosphodiesterase, while theophylline inhibited these enzymes similarly. However, cyclic GMP phosphodiesterases in all tissues examined were inhibited similarly, not only by theophylline but also by papaverine.", "contents": "Cyclic 3',5'-AMP phosphodiesterase of rabbit aorta. Cyclic AMP and cyclic GMP phosphodiesterase activities (3' : 5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) were demonstrated in the isolated intima, media, and adventitia of rabbit aorta. The activity for cyclic AMP hydrolysis in the intima was 2.7-fold higher than that for cyclic GMP hydrolysis. The activity for cyclic AMP hydrolysis in the media was approximately equal to that for cyclic GMP hydrolysis, but in the adventitia, cyclic GMP hydrolytic activity was 2.1-fold higher than cyclic AMP hydrolytic activity. Distribution of the activator of the phosphodiesterase was studied in the three layers. Each layer contained the activator. The activator was predominantly localized in the smooth muscle layer (the media). The effect of the activator and Ca2+ on the media cyclic AMP and cyclic GMP phosphodiesterase was also briefly studied. The activity of the cyclic GMP phosphodiesterase was stimulated by micromolar concentration of Ca2+ in the presence of the activator. However, the activity of the cyclic AMP phosphodiesterase was not significantly stimulated by Ca2+ up to 100 muM in the presence of the activator. Above 90% of cyclic nucleotide phosphodiesterase activity in the whole aorta was found to be derived from the media. A major portion (60-70%) of the media enzyme was found in 105 000 times g supernatant. Cyclic AMP phosphodiesterase in the supernatant was partially purified through Sepharose 6B column chromatography and partially separated from cyclic GMP phosphodiesterase. Using a partially purified preparation from the 105 000 times g supernatant the main kinetic parameters were specified as follows: 1) The pH optimum was found to be about 9.0 using Tris-maleate buffer. The maximum stimulation of the enzyme by Mg2+ was achieved at 4mM of MgC12. 2) High concentration of cyclic GMP (0.1 mM) inhibited noncompetitively the enzyme activity, and the activity was not stimulated at any tested concentration of cyclic GMP. 3) Activity-substrate concentration relationship revealed a high affinity (Km equals 1.0 muM) and low affinity (Km equals 45 muM) for cyclic AMP. The homogenate and 105 000 times g supernatant of the media also showed non-linear kinetics similar to the Sepharose 6B preparation and their apparent Km values for cyclic AMP hydrolysis were 1.2 muM and 36-40 muM and an enzyme extracted by sonication from 105 000 times g precipitate also exhibited non-linear kinetics (Km equals 5.1 muM and 70 muM). 4) Papaverine exhibited much stronger inhibition on the aorta cyclic AMP phosphodiesterase (50% inhibition of the intima enzyme, I5 o at 0.62 muM, I5 o of the media at 0.62 muM and I5 o of the adventitia at 1.0 muM) than on the brain (I5 o at 8.5 muM) and serum (I5 o at 20 muM) cyclic AMP phosphodiesterase, while theophylline inhibited these enzymes similarly. However, cyclic GMP phosphodiesterases in all tissues examined were inhibited similarly, not only by theophylline but also by papaverine."} {"id": "PMID:164220", "title": "Mammalian carbamyl phosphate : glucose phosphotransferase and glucose-6-phosphate phosphohydrolase: extended tissue distribution.", "content": "Carbamyl phosphate : glucose phosphotransferase and glucose-6-phosphate (Glc-6-P) phosphohydrolase activities have beeh demonstrated in pancreas, adrenals, brain, testes, spleen, and lung. Catalysis of these activities by classical multifunctional glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase; EC 3.1.3.9) has been firmly established for the first four of these tissues on the basis of characteristic catalytic properties of the transferase pH-activity profiles, apparent Km values for carbamyl phosphate and glucose, substrate specificity, susceptibility to inhibition by molybdate, and activation by deoxycholate. Additional such activity due to non-specific acid (and alkaline) phosphatase action also is indicated at very high glucose concentrations. The possible physiological significance of the newly-elucidated presence of glucose-6-phosphatase-phosphotransferase in these various tissues, in addition to previously extensively studied liver, kidney, and mucosa of small intestine, is discussed briefly.", "contents": "Mammalian carbamyl phosphate : glucose phosphotransferase and glucose-6-phosphate phosphohydrolase: extended tissue distribution. Carbamyl phosphate : glucose phosphotransferase and glucose-6-phosphate (Glc-6-P) phosphohydrolase activities have beeh demonstrated in pancreas, adrenals, brain, testes, spleen, and lung. Catalysis of these activities by classical multifunctional glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase; EC 3.1.3.9) has been firmly established for the first four of these tissues on the basis of characteristic catalytic properties of the transferase pH-activity profiles, apparent Km values for carbamyl phosphate and glucose, substrate specificity, susceptibility to inhibition by molybdate, and activation by deoxycholate. Additional such activity due to non-specific acid (and alkaline) phosphatase action also is indicated at very high glucose concentrations. The possible physiological significance of the newly-elucidated presence of glucose-6-phosphatase-phosphotransferase in these various tissues, in addition to previously extensively studied liver, kidney, and mucosa of small intestine, is discussed briefly."} {"id": "PMID:164221", "title": "The attack mechanism of an exo-1,3-beta-glucosidase from Basidiomycete sp. QM 806.", "content": "The attack mechanism of a purified exo-1,3-beta glucosidase (1,3-beta-D-glucan glucohydrolase, EC 3.2.1.58) was investigated by using as a substrate a mixture of two structurally characterized periodate-oxidized and reduced unbranched 1,3-beta-D-glucans which differed only at the reducing terminal. The substrates, derivatives of laminarin, were altered only at the terminals due to resistance of the internal (1 leads to 3)-linked glucosyl residues to periodate oxidation. Each glucan has only a single and identical altered non-reducing terminal per molecule. Upon enzymatic hydrolysis, one molar equivalent of glycerol was produced from the altered non-reducing terminal of each substrate molecule attacked. Using glycerol as an indication of the number of chains acted upon, the quantity of D-glucose produced from the internal residues was used to determine the extent to which a chain was initially attacked. The glucose to glycerol ratio during the course of the hydrolysis indicates that the enzyme proceeds by a multiple-attack mechanism where four glucosyl residues are successively removed per encounter from the non-reducing terminal of each substrate molecule.", "contents": "The attack mechanism of an exo-1,3-beta-glucosidase from Basidiomycete sp. QM 806. The attack mechanism of a purified exo-1,3-beta glucosidase (1,3-beta-D-glucan glucohydrolase, EC 3.2.1.58) was investigated by using as a substrate a mixture of two structurally characterized periodate-oxidized and reduced unbranched 1,3-beta-D-glucans which differed only at the reducing terminal. The substrates, derivatives of laminarin, were altered only at the terminals due to resistance of the internal (1 leads to 3)-linked glucosyl residues to periodate oxidation. Each glucan has only a single and identical altered non-reducing terminal per molecule. Upon enzymatic hydrolysis, one molar equivalent of glycerol was produced from the altered non-reducing terminal of each substrate molecule attacked. Using glycerol as an indication of the number of chains acted upon, the quantity of D-glucose produced from the internal residues was used to determine the extent to which a chain was initially attacked. The glucose to glycerol ratio during the course of the hydrolysis indicates that the enzyme proceeds by a multiple-attack mechanism where four glucosyl residues are successively removed per encounter from the non-reducing terminal of each substrate molecule."} {"id": "PMID:164222", "title": "Cold inactivation of glyceraldehyde-phosphate dehydrogenase from rat skeletal muscle.", "content": "Inactivation of apo-glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase(phosphorylating) (EC 1.2.1.12) from rat skeletal muscle at 4 degrees C in 0.15 M NaC1, 5 mM EDTA, 4 mM 2-mercaptoethanol pH 7.2 is a first-order reaction. The rate constant of inactivation depends on protein concentration. With one molecule of NAD bound per tetrameric enzyme, a 50 per cent loss in activity is observed and the rate constant of inactivation becomes independent of the protein concentration over a 30-fold range. Two moles of NAD bound per mole of enzyme fully protect it against inactivation. NADH affords a cooperative effect on enzyme structure similar to that of NAD. Inactivation of 7.8 S apoenzyme is reflected in its dissociation into 4.8-S dimers. In the case of enzyme-NAD1 complex, no direct relationship between the extent of inactivation and dissociation is observed, suggesting that these two processes do not occur simultaneously; we may say that dissociation is slower than inactivation. A mechanism in which the rate-limiting step for inactivation is a conformational change in the tetramer occurring prior to dissociation and affecting only the structure of the non-liganded dimer, is consistent with the experimental observations. Inorganic phosphate protects apoenzyme against inactivation. Its effect is shown to be due to the anion binding at specific sites on the protein with a dissociation constant of 2.6 plus or minus 0.4 mM. The NaC1-induced cold inactivation of glyceraldehyde-phosphate dehydrogenase is fully reversible at 25 degrees C in the presence of 20 mM dithiothreitol and 50 mM inorganic phosphate. The rate of reactivation is independent of protein concentration. Inactivated enzyme retains the ability to bind specific antibodies produced in rabbits, but diminishes its precipitating capability.", "contents": "Cold inactivation of glyceraldehyde-phosphate dehydrogenase from rat skeletal muscle. Inactivation of apo-glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase(phosphorylating) (EC 1.2.1.12) from rat skeletal muscle at 4 degrees C in 0.15 M NaC1, 5 mM EDTA, 4 mM 2-mercaptoethanol pH 7.2 is a first-order reaction. The rate constant of inactivation depends on protein concentration. With one molecule of NAD bound per tetrameric enzyme, a 50 per cent loss in activity is observed and the rate constant of inactivation becomes independent of the protein concentration over a 30-fold range. Two moles of NAD bound per mole of enzyme fully protect it against inactivation. NADH affords a cooperative effect on enzyme structure similar to that of NAD. Inactivation of 7.8 S apoenzyme is reflected in its dissociation into 4.8-S dimers. In the case of enzyme-NAD1 complex, no direct relationship between the extent of inactivation and dissociation is observed, suggesting that these two processes do not occur simultaneously; we may say that dissociation is slower than inactivation. A mechanism in which the rate-limiting step for inactivation is a conformational change in the tetramer occurring prior to dissociation and affecting only the structure of the non-liganded dimer, is consistent with the experimental observations. Inorganic phosphate protects apoenzyme against inactivation. Its effect is shown to be due to the anion binding at specific sites on the protein with a dissociation constant of 2.6 plus or minus 0.4 mM. The NaC1-induced cold inactivation of glyceraldehyde-phosphate dehydrogenase is fully reversible at 25 degrees C in the presence of 20 mM dithiothreitol and 50 mM inorganic phosphate. The rate of reactivation is independent of protein concentration. Inactivated enzyme retains the ability to bind specific antibodies produced in rabbits, but diminishes its precipitating capability."} {"id": "PMID:164223", "title": "Electron-electron double resonance measurements on xanthine oxidase.", "content": "Electron-electron double resonance measurements were carried out on milk xanthine oxidase (xanthine:oxygen oxidoreductase EC 1.2.3.2) and the spectra obtained supported a previous model, based on EPR data, proposing a spin-spin interaction between unpaired electrons associated with Fe-S and Mo. The technique demonstrated that the additional apparently isotropic, splitting in the Mo EPR spectra observed at low temperature is produced by a single site giving two spectra interconverting at a rate consistent with the Fe-S spin lattice relaxation time. Other data concerning the model and the relaxation behaviour of the species are discussed.", "contents": "Electron-electron double resonance measurements on xanthine oxidase. Electron-electron double resonance measurements were carried out on milk xanthine oxidase (xanthine:oxygen oxidoreductase EC 1.2.3.2) and the spectra obtained supported a previous model, based on EPR data, proposing a spin-spin interaction between unpaired electrons associated with Fe-S and Mo. The technique demonstrated that the additional apparently isotropic, splitting in the Mo EPR spectra observed at low temperature is produced by a single site giving two spectra interconverting at a rate consistent with the Fe-S spin lattice relaxation time. Other data concerning the model and the relaxation behaviour of the species are discussed."} {"id": "PMID:164224", "title": "Spin label and lanthanide binding sites on glyceraldehyde-3-phosphate dehydrogenase.", "content": "The electron spin resonance spectrum of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase spin-labelled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl has two components. One component is due to a spin label highly immobilized on the enzyme surface and the other to a nitroxyl group able to tumble more rapidly. The spin-labelled enzyme is inactive. Selective modification of the active site cysteine residue (149) and determinations of total sulphydryl content implicate this residue as the site of the immobile spin-label. The mobile spin label is attached to another sulphydryl group. Crystallographic studies on the human muscle enzyme (Watson, H.C., Duee, E. and Mercer, W.D. (1972) Nat. New Biol., 240, 130) have located a binding site for samarium ion in the active centre. Addition of the paramagnetic gadolinium ion to spin-labelled enzyme reduces the intensity of both the spin label signals (by 72% for the mobile and by 11% for the immobile component). This indicates that the metal ion site (Kd equals 0.7 mM) is close to both types of spin label. Measurements of the effect of gadolinium-protein binding on the relaxation rate of solvent water protons enable the enzyme-bound spin label-metal ion distances to be tentatively estimated as 15 angstrom.", "contents": "Spin label and lanthanide binding sites on glyceraldehyde-3-phosphate dehydrogenase. The electron spin resonance spectrum of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase spin-labelled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl has two components. One component is due to a spin label highly immobilized on the enzyme surface and the other to a nitroxyl group able to tumble more rapidly. The spin-labelled enzyme is inactive. Selective modification of the active site cysteine residue (149) and determinations of total sulphydryl content implicate this residue as the site of the immobile spin-label. The mobile spin label is attached to another sulphydryl group. Crystallographic studies on the human muscle enzyme (Watson, H.C., Duee, E. and Mercer, W.D. (1972) Nat. New Biol., 240, 130) have located a binding site for samarium ion in the active centre. Addition of the paramagnetic gadolinium ion to spin-labelled enzyme reduces the intensity of both the spin label signals (by 72% for the mobile and by 11% for the immobile component). This indicates that the metal ion site (Kd equals 0.7 mM) is close to both types of spin label. Measurements of the effect of gadolinium-protein binding on the relaxation rate of solvent water protons enable the enzyme-bound spin label-metal ion distances to be tentatively estimated as 15 angstrom."} {"id": "PMID:164225", "title": "Demonstration by EPR spectroscopy of the functional role of iron in soybean lipoxygenase-1.", "content": "1. The EPR spectrum at 15 degrees K of soybean lipoxygenase-1 in borate buffer pH 9.0 has been studied in relation to the presence of substrate (linoleic acid), product (13-L-hydroperoxylinoleic acid) and oxygen. 2. The addition of 13-L-hydroperoxylinoleic acid to lipoxygenase-1 at pH 9.0 gives rise to the appearance of EPR lines at g equals 7.5, 6.2, 5.9 and 2.0, and an increased signal at g equals 4.3. 3. In view of the effect of the end product on both the kinetic lag period of the aerobic reaction and the fluorescence of the enzyme, it is concluded that 13-L-hydroperoxylinoleic acid is required for the activation of soybean lipoxygenase-1. Thus it is proposed that the enzyme with iron in the ferric state is the active species. 4. A reaction scheme is presented in which the enzyme alternatingly exists in the ferric and ferrous states for both the aerobic and anaerobic reaction.", "contents": "Demonstration by EPR spectroscopy of the functional role of iron in soybean lipoxygenase-1. 1. The EPR spectrum at 15 degrees K of soybean lipoxygenase-1 in borate buffer pH 9.0 has been studied in relation to the presence of substrate (linoleic acid), product (13-L-hydroperoxylinoleic acid) and oxygen. 2. The addition of 13-L-hydroperoxylinoleic acid to lipoxygenase-1 at pH 9.0 gives rise to the appearance of EPR lines at g equals 7.5, 6.2, 5.9 and 2.0, and an increased signal at g equals 4.3. 3. In view of the effect of the end product on both the kinetic lag period of the aerobic reaction and the fluorescence of the enzyme, it is concluded that 13-L-hydroperoxylinoleic acid is required for the activation of soybean lipoxygenase-1. Thus it is proposed that the enzyme with iron in the ferric state is the active species. 4. A reaction scheme is presented in which the enzyme alternatingly exists in the ferric and ferrous states for both the aerobic and anaerobic reaction."} {"id": "PMID:164226", "title": "Non-allosteric regulation of the uridine kinase from seeds of Zea mays.", "content": "Uridine kinase (ATP: uridine 5'-phosphotransferase, EC 2.7.1.48) has been partially purified from ungerminated hybrid corn seed. It is associated with a soluble high molecular weight fraction from which it apparently cannot be dissociated without loss of activity. The stability of the enzyme is enhanced by the addition of dithiothreitol, glycerol and nucleotide substrate. The nucleoside specificity of the enzyme is limited to nucleosides containing pyrimidine and ribose moieties, such as uridine and cytidine. High concentrations of nucleosides cause substrate inhibition, however. The Km values for uridine and cytidine are 53 muM and 125 muM, respectively, and under subsaturating conditions uridine is phosphorylated about five times faster than cytidine. The reaction follows an ordered Bi Bi kinetic pattern, with ATP and ADP in competition for the free form of the enzyme. Purine, but not pyrimidine, nucleoside triphosphates serve as phosphate donors without regard to the sugar moiety. However, all of these triphosphates appear to compete for the same site on the enzyme. (Km ATP equals 590 muM, Km (app) GTP equals 61 muM, and CTP and UTP are linear competitive inhibitors against ATP, with Ki values of 60 muM and 240 muM, respectively.) Therefore, end product control of uridine kinase apparently does not involve allosteric sites, but instead is envisioned as simple competition between relatively effective or ineffective phosphate donors for a position on the enzyme.", "contents": "Non-allosteric regulation of the uridine kinase from seeds of Zea mays. Uridine kinase (ATP: uridine 5'-phosphotransferase, EC 2.7.1.48) has been partially purified from ungerminated hybrid corn seed. It is associated with a soluble high molecular weight fraction from which it apparently cannot be dissociated without loss of activity. The stability of the enzyme is enhanced by the addition of dithiothreitol, glycerol and nucleotide substrate. The nucleoside specificity of the enzyme is limited to nucleosides containing pyrimidine and ribose moieties, such as uridine and cytidine. High concentrations of nucleosides cause substrate inhibition, however. The Km values for uridine and cytidine are 53 muM and 125 muM, respectively, and under subsaturating conditions uridine is phosphorylated about five times faster than cytidine. The reaction follows an ordered Bi Bi kinetic pattern, with ATP and ADP in competition for the free form of the enzyme. Purine, but not pyrimidine, nucleoside triphosphates serve as phosphate donors without regard to the sugar moiety. However, all of these triphosphates appear to compete for the same site on the enzyme. (Km ATP equals 590 muM, Km (app) GTP equals 61 muM, and CTP and UTP are linear competitive inhibitors against ATP, with Ki values of 60 muM and 240 muM, respectively.) Therefore, end product control of uridine kinase apparently does not involve allosteric sites, but instead is envisioned as simple competition between relatively effective or ineffective phosphate donors for a position on the enzyme."} {"id": "PMID:164227", "title": "Comparative study of two ATP : L-arginine phosphotransferases of molecular weight 84 000.", "content": "Solen ensisensis muscle arginine kinase (ATP : L-arginine phosphotransferase, EC 2.7.3.3) was isolated in an homogeneous state. Its molecular weight was found to be about 80 000. The properties of this enzyme were compared with those of arginine kinase from Sipunculus nudus, an enzyme which also has a molecular weight of about 80 000. Both enzymes have several reactive thiol groups (8 thiol groups in the Solen kinase and 12 in the Sipunculus enzyme were titrateable with 5,5'-dithio-bis-(2-nitrobenzoic) acid and histidine residues (both enzymes have 6 reactive histidine residues). These kinases were, therefore, highly susceptible to oxidation. Both enzymes show the same pH optimum and absolute specificity towards the guanidine substrate, L-arginine. The reaction kinetics of both enzymes are of the sequential type. In the presence of alpha-aminoacids of Mg2+-ADP, similar spectral effects were obtained. The enzymes differ in their enzymic activities and in their rate of recovery following urea denaturation. The most important difference that appeared to be a special feature of the Sipunculus enzyme is that the spectrum of the Mg2+-ADP-enzyme complex is strongly intensified by L-arginine.", "contents": "Comparative study of two ATP : L-arginine phosphotransferases of molecular weight 84 000. Solen ensisensis muscle arginine kinase (ATP : L-arginine phosphotransferase, EC 2.7.3.3) was isolated in an homogeneous state. Its molecular weight was found to be about 80 000. The properties of this enzyme were compared with those of arginine kinase from Sipunculus nudus, an enzyme which also has a molecular weight of about 80 000. Both enzymes have several reactive thiol groups (8 thiol groups in the Solen kinase and 12 in the Sipunculus enzyme were titrateable with 5,5'-dithio-bis-(2-nitrobenzoic) acid and histidine residues (both enzymes have 6 reactive histidine residues). These kinases were, therefore, highly susceptible to oxidation. Both enzymes show the same pH optimum and absolute specificity towards the guanidine substrate, L-arginine. The reaction kinetics of both enzymes are of the sequential type. In the presence of alpha-aminoacids of Mg2+-ADP, similar spectral effects were obtained. The enzymes differ in their enzymic activities and in their rate of recovery following urea denaturation. The most important difference that appeared to be a special feature of the Sipunculus enzyme is that the spectrum of the Mg2+-ADP-enzyme complex is strongly intensified by L-arginine."} {"id": "PMID:164228", "title": "Kinetic properties and related changes of molecular weight in a fructokinase from Streptomyces violaceoruber.", "content": "1. A study of the initial reaction rates at variable substrate concentrations and of the molecular weight of the enzyme in the presence of different effectors, has been carried out using fructokinase (ATP: fructose 6-phosphotransferase, EC 2.7.1.4) from Streptomyces violaceoruber. 2. Saturation curves for MgATP or CoATP are sigmoidal and they change to hyperbolic in the presence of 10 mM Mg2+ or Co2+ in excess over the nucleoside triphosphate. 3. Saturation cuvves for fructose show intermediary plateaux at high (but not at low) concentrations of ATP or Mg2+. 4. The molecular weight of the enzyme in the presence of high concentrations of MgATP is 80 000. In the presence of fructose, and/or Mg2+, the molecular weight is 20 000. 5. The effects of MgADP, uncomplexed ADP or ATP, and low concentrations of detergent on the kinetics have been studied. The results are interpreted as showing the existence of cooperative effects.", "contents": "Kinetic properties and related changes of molecular weight in a fructokinase from Streptomyces violaceoruber. 1. A study of the initial reaction rates at variable substrate concentrations and of the molecular weight of the enzyme in the presence of different effectors, has been carried out using fructokinase (ATP: fructose 6-phosphotransferase, EC 2.7.1.4) from Streptomyces violaceoruber. 2. Saturation curves for MgATP or CoATP are sigmoidal and they change to hyperbolic in the presence of 10 mM Mg2+ or Co2+ in excess over the nucleoside triphosphate. 3. Saturation cuvves for fructose show intermediary plateaux at high (but not at low) concentrations of ATP or Mg2+. 4. The molecular weight of the enzyme in the presence of high concentrations of MgATP is 80 000. In the presence of fructose, and/or Mg2+, the molecular weight is 20 000. 5. The effects of MgADP, uncomplexed ADP or ATP, and low concentrations of detergent on the kinetics have been studied. The results are interpreted as showing the existence of cooperative effects."} {"id": "PMID:164229", "title": "Properties of cyclic nucleotide phosphodiesterase in the central nervous system of Manduca sexta.", "content": "The properties of cyclic nucleotide phosphodiesterase were studied in soluble and particulate fractions from the central nervous system of Manduca sexta (Lepidoptera: Sphingidae). It was determined that: (1) The highest levels of phosphodiesterase occur in nervous tissue. (2) The total and specific enzyme activities of larval and adult brains are greater than those of the remaining ganglia. (3) Specific central nervous sy stem phosphodiesterase activities of the adult are lower than those of the larva, but both protein and total phosphodiesterase contents are considerably greater in the adult central nervous system. (4) Mg2+ is not absolutely required for either cyclic AMP-phosphodiesterase or cyclic GMP-phosphodiesterase activity. (5) Phosphodiesterase is inhibited by a variety of physiological and non-physiological compounds, nucleoside triphosphates being particularly effective; Some potent inhibitors of mammalian phosphodiesterase are comparatively ineffective toward Manduca sexta phosphodiesterase. (6) Kinetic analyses of soluble and particulate phosphodiesterase revealed non-linear double-reciprocal plots for the hydrolysis of both cyclic AMP and cyclic GMP, with Michaelis constants of approximately 10 mu M and 20 mu M; (7) The hydrolysis of both cyclic nucleotides appears in part to be the function of a single enzyme or related enzymes in the insect central nervous system. It follows that the intracellular level of one cyclic nucleotide may influence the concentration of the other by inhibiting its DEGRADATION.", "contents": "Properties of cyclic nucleotide phosphodiesterase in the central nervous system of Manduca sexta. The properties of cyclic nucleotide phosphodiesterase were studied in soluble and particulate fractions from the central nervous system of Manduca sexta (Lepidoptera: Sphingidae). It was determined that: (1) The highest levels of phosphodiesterase occur in nervous tissue. (2) The total and specific enzyme activities of larval and adult brains are greater than those of the remaining ganglia. (3) Specific central nervous sy stem phosphodiesterase activities of the adult are lower than those of the larva, but both protein and total phosphodiesterase contents are considerably greater in the adult central nervous system. (4) Mg2+ is not absolutely required for either cyclic AMP-phosphodiesterase or cyclic GMP-phosphodiesterase activity. (5) Phosphodiesterase is inhibited by a variety of physiological and non-physiological compounds, nucleoside triphosphates being particularly effective; Some potent inhibitors of mammalian phosphodiesterase are comparatively ineffective toward Manduca sexta phosphodiesterase. (6) Kinetic analyses of soluble and particulate phosphodiesterase revealed non-linear double-reciprocal plots for the hydrolysis of both cyclic AMP and cyclic GMP, with Michaelis constants of approximately 10 mu M and 20 mu M; (7) The hydrolysis of both cyclic nucleotides appears in part to be the function of a single enzyme or related enzymes in the insect central nervous system. It follows that the intracellular level of one cyclic nucleotide may influence the concentration of the other by inhibiting its DEGRADATION."} {"id": "PMID:164230", "title": "Cyclic nucleotide-stimulable protein kinases in the central nervous sytem of Manduca sexta.", "content": "Cyclic nucleotide-stimulable protein kinase (EC 1.7.1.37) has been studied in crude extracts from the central nervous system of the tobacco hornworm Manduca sexta (Lepidoptera: Sphingidae). The insect kinase was fulfhydryl-sensitive and required Mg-2+ for optimal activity. Polyacrylamide gel electrophoresis of supernatants demonstrated the presence of multiple kinases in the larval nerve cord. At low concentrations, cyclic AMP was a much more potent activator of soluble and particulate activities than was cyclic GMP. The specific activity of coluble kinase and the magnitude of its activations by cyclic AMP were greater in the adult than in the larval central nervous system. The exogenous protein substrate specificity of the insect enzyme was similar to that of rat brain kinase with the sole exception that protamine was more readily phosphorylated than histone by nerve cord kinase. It was observed that cyclic AMP lowered the Km of Manduca sexta kinase for ATP, a phenomenon which is apparently nervous tissue=specific in mammals. An effective inhibitor of cyclic AMP-dependent protein kinase was prepared from the larval central nervous system.", "contents": "Cyclic nucleotide-stimulable protein kinases in the central nervous sytem of Manduca sexta. Cyclic nucleotide-stimulable protein kinase (EC 1.7.1.37) has been studied in crude extracts from the central nervous system of the tobacco hornworm Manduca sexta (Lepidoptera: Sphingidae). The insect kinase was fulfhydryl-sensitive and required Mg-2+ for optimal activity. Polyacrylamide gel electrophoresis of supernatants demonstrated the presence of multiple kinases in the larval nerve cord. At low concentrations, cyclic AMP was a much more potent activator of soluble and particulate activities than was cyclic GMP. The specific activity of coluble kinase and the magnitude of its activations by cyclic AMP were greater in the adult than in the larval central nervous system. The exogenous protein substrate specificity of the insect enzyme was similar to that of rat brain kinase with the sole exception that protamine was more readily phosphorylated than histone by nerve cord kinase. It was observed that cyclic AMP lowered the Km of Manduca sexta kinase for ATP, a phenomenon which is apparently nervous tissue=specific in mammals. An effective inhibitor of cyclic AMP-dependent protein kinase was prepared from the larval central nervous system."} {"id": "PMID:164231", "title": "Interaction of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein with DNAs of different base composition.", "content": "The changes in absorption spectra in the visible region observed on adding different naturally occurring and synthetic DNA duplexes to solutions of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein indicate that the mercurial reacts with polynucleotides of this type. The reaction is reversible as proved by adding excess of KCN which restores the original spectra of the free dye. The interaction is characterised also by quenching of the fluorescence of the dye and the induction of optical activity in it. The extent of these spectral effects depends strongly on the (A+T) content of the complexed DNA and decreased in the order: poly [d(A-T)], Clostridium perfringens DAN, Escherichia coli DNA, Micrococcus luteus DNA and poly(dC). From equilibrium-dialysis experiments the same order in affinity is obtained when these poly-nucleotides are at equilibrium with the same concentration of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein. From the changes produced by different mercurials in the ORD spectra and viscosity of a DNA solution it has been concluded that 4,5-dibromo-2,7-di(acetatomercuri)-fluorescein does not cause any drastic alteration of the secondary structure of DNA.", "contents": "Interaction of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein with DNAs of different base composition. The changes in absorption spectra in the visible region observed on adding different naturally occurring and synthetic DNA duplexes to solutions of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein indicate that the mercurial reacts with polynucleotides of this type. The reaction is reversible as proved by adding excess of KCN which restores the original spectra of the free dye. The interaction is characterised also by quenching of the fluorescence of the dye and the induction of optical activity in it. The extent of these spectral effects depends strongly on the (A+T) content of the complexed DNA and decreased in the order: poly [d(A-T)], Clostridium perfringens DAN, Escherichia coli DNA, Micrococcus luteus DNA and poly(dC). From equilibrium-dialysis experiments the same order in affinity is obtained when these poly-nucleotides are at equilibrium with the same concentration of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein. From the changes produced by different mercurials in the ORD spectra and viscosity of a DNA solution it has been concluded that 4,5-dibromo-2,7-di(acetatomercuri)-fluorescein does not cause any drastic alteration of the secondary structure of DNA."} {"id": "PMID:164232", "title": "The purification and properties of superoxide dismutase from a blue-green alga.", "content": "Soluble extracts of Plectonema boryanum have been shown to contain a single, electrophoretically distinct, superoxide dismutase. The enzyme has been isolated and has been found to be an iron-containing enzyme similar to that described from the periplasm of Escherichia coli. It contains 1 Fe3+/mole of enzyme. The molecular weight was approximately 36 500, and the enzyme appeared to be composed of two subunits of equal size joined by non-covalent interactions. ESR data are presented, as are the results of amino acid analysis.", "contents": "The purification and properties of superoxide dismutase from a blue-green alga. Soluble extracts of Plectonema boryanum have been shown to contain a single, electrophoretically distinct, superoxide dismutase. The enzyme has been isolated and has been found to be an iron-containing enzyme similar to that described from the periplasm of Escherichia coli. It contains 1 Fe3+/mole of enzyme. The molecular weight was approximately 36 500, and the enzyme appeared to be composed of two subunits of equal size joined by non-covalent interactions. ESR data are presented, as are the results of amino acid analysis."} {"id": "PMID:164233", "title": "Studies on the conformational changes of metalloproteins induced by electrons in water-ethylene glycol solutions at low temperatures. III. Adrenal ferredoxin.", "content": "The reduction of adrenal ferredoxin (adrenodoxin) at low temperatures was investigated in order to separate local modifications of the active centre of the protein on its reduction, from the conformational transition which seems to accompany the change of the redox state of the irons; The ESR spectra of the states of the protein, where the reduced active centre is to be found by the \"oxidized\" conformation of the apoprotein, were obtained. The transition from the states of the protein to the state which occurs on its chemical reduction at room temperature was also investigated. The results of the work support the view that conformational changes in proteins (enzymes) which take place while they are functioning proceed after modifications of the active centres (change of the redox state, adsorption of a substrate, etc.), and are essentially caused by them. Adrenal ferredoxin was the third subject in our studies of the intermediate states of proteins which appear after reduction of their active centres by means of electrons trapped in water-ethylene glycol mixtures at the temperature of liquid nitrogen [1, 2]. In the reduced state, the active centre of the protein has an ESR signal with a g-factor of 1.94 [3, 4] which is convenient for our purposes.", "contents": "Studies on the conformational changes of metalloproteins induced by electrons in water-ethylene glycol solutions at low temperatures. III. Adrenal ferredoxin. The reduction of adrenal ferredoxin (adrenodoxin) at low temperatures was investigated in order to separate local modifications of the active centre of the protein on its reduction, from the conformational transition which seems to accompany the change of the redox state of the irons; The ESR spectra of the states of the protein, where the reduced active centre is to be found by the \"oxidized\" conformation of the apoprotein, were obtained. The transition from the states of the protein to the state which occurs on its chemical reduction at room temperature was also investigated. The results of the work support the view that conformational changes in proteins (enzymes) which take place while they are functioning proceed after modifications of the active centres (change of the redox state, adsorption of a substrate, etc.), and are essentially caused by them. Adrenal ferredoxin was the third subject in our studies of the intermediate states of proteins which appear after reduction of their active centres by means of electrons trapped in water-ethylene glycol mixtures at the temperature of liquid nitrogen [1, 2]. In the reduced state, the active centre of the protein has an ESR signal with a g-factor of 1.94 [3, 4] which is convenient for our purposes."} {"id": "PMID:164234", "title": "Studies on plasma membranes. XXII. Fatty acid profiles of lipid classes in plasma membranes of rat and mouse livers and hepatomas.", "content": "Plasma membranes were isolated from rat and mouse livers, a transplanted rat hepatoma, two transplanted mouse hepatomas and spontaneous mouse hepatomas. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophosphatidylcholine, free fatty acids and triglycerides were separated and their fatty acid profiles determined. The various lipid classes of rat and mouse liver plasma membranes each demonstrated more or less specific fatty acid profiles. The number of double bonds decreased in the order: phosphatidylserine greater than or equal to phosphatidylethanolamine greater than phosphatidylinositol greater than phosphatidylcholine greater than or equal to sphingomyelin and lysophosphatidylcholine. Small species differences were noted in most lipid classes. A marked sex difference was observed in sphingomyelin of mouse liver membranes but in none of the phospholipids of rat liver membranes. The increased cholesterol content of all hepatoma versus liver plasma membranes was accompanied by a decrease of fatty acyl poly-unsaturation in most lipid classes of the rat hepatoma but not of the mouse hepatoma membranes. The fatty acid profiles of the mouse hepatoma membranes deviated much less from those of mouse liver than did the pattern of rat hepatoma versus rat liver. The results were discussed in relation to lipid fluidity of which fatty acyl unsaturation and cholesterol are the main parameters.", "contents": "Studies on plasma membranes. XXII. Fatty acid profiles of lipid classes in plasma membranes of rat and mouse livers and hepatomas. Plasma membranes were isolated from rat and mouse livers, a transplanted rat hepatoma, two transplanted mouse hepatomas and spontaneous mouse hepatomas. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophosphatidylcholine, free fatty acids and triglycerides were separated and their fatty acid profiles determined. The various lipid classes of rat and mouse liver plasma membranes each demonstrated more or less specific fatty acid profiles. The number of double bonds decreased in the order: phosphatidylserine greater than or equal to phosphatidylethanolamine greater than phosphatidylinositol greater than phosphatidylcholine greater than or equal to sphingomyelin and lysophosphatidylcholine. Small species differences were noted in most lipid classes. A marked sex difference was observed in sphingomyelin of mouse liver membranes but in none of the phospholipids of rat liver membranes. The increased cholesterol content of all hepatoma versus liver plasma membranes was accompanied by a decrease of fatty acyl poly-unsaturation in most lipid classes of the rat hepatoma but not of the mouse hepatoma membranes. The fatty acid profiles of the mouse hepatoma membranes deviated much less from those of mouse liver than did the pattern of rat hepatoma versus rat liver. The results were discussed in relation to lipid fluidity of which fatty acyl unsaturation and cholesterol are the main parameters."} {"id": "PMID:164235", "title": "The removal of cholesterol from aortic smooth muscle cells in culture and Landschutz ascites cells by fractions of human high-density apolipoprotein.", "content": "Ascites cells were labeled by intraperitoneal injection of [3H]cholesterol and aortic smooth muscle cells by addition of [3H]cholesterol to the serum component of the culture medium. The release of cholesterol from cells into a serum-free medium supplemented with the various \"acceptors\" was studied using ascites cells in suspension and aortic smooth muscle cells in a multilayer culture. Unfractionated human high-density apolipoprotein was somewhat more effective in the removal of labeled cellular free cholesterol, in both cell types, than apolipoprotein derived from rat high-density lipoprotein. Following separation of human high-density apolipoprotein into four fractions by Sephadex chromatography, the effect of each fraction on the removal of cellular cholesterol from ascites cells was studied. The individual fractions had a lower capacity for cholesterol removal than the original unfractionated high-density apolipoprotein and the lowest activity was detected in Fraction II which comprised 75% of the total apolipoprotein. The effectiveness to remove cholesterol could be restored to all the fractions, as well as enhanced, by addition of sonicated suspensions of lecithin or sphingomyelin, which by themselves promoted a more limited removal of cellular cholesterol. Negatively stained preparations of mixtures of the four fractions and sonicated dispersion of lecithin were shown to consist of vesicles and discs of various sizes. Addition of the apolipoprotein fractions (especially Fractions II and IV) to sonicated dispersion of sphingomyelin resulted in a pronounced formation of discs which showed a high tendency towards stack formation. Mixtures of Fraction II and lecithin or sphingomyelin were effective in the release of cellular cholesterol from multilayers of aortic smooth muscle cells in culture. These results show the feasibility of net removal of cholesterol from cells which grow in a form resembling a tissue and thus provide a model to study the role of apolipoprotein-phospholipid mixtures in cholesterol removal from cells and tissues in vivo.", "contents": "The removal of cholesterol from aortic smooth muscle cells in culture and Landschutz ascites cells by fractions of human high-density apolipoprotein. Ascites cells were labeled by intraperitoneal injection of [3H]cholesterol and aortic smooth muscle cells by addition of [3H]cholesterol to the serum component of the culture medium. The release of cholesterol from cells into a serum-free medium supplemented with the various \"acceptors\" was studied using ascites cells in suspension and aortic smooth muscle cells in a multilayer culture. Unfractionated human high-density apolipoprotein was somewhat more effective in the removal of labeled cellular free cholesterol, in both cell types, than apolipoprotein derived from rat high-density lipoprotein. Following separation of human high-density apolipoprotein into four fractions by Sephadex chromatography, the effect of each fraction on the removal of cellular cholesterol from ascites cells was studied. The individual fractions had a lower capacity for cholesterol removal than the original unfractionated high-density apolipoprotein and the lowest activity was detected in Fraction II which comprised 75% of the total apolipoprotein. The effectiveness to remove cholesterol could be restored to all the fractions, as well as enhanced, by addition of sonicated suspensions of lecithin or sphingomyelin, which by themselves promoted a more limited removal of cellular cholesterol. Negatively stained preparations of mixtures of the four fractions and sonicated dispersion of lecithin were shown to consist of vesicles and discs of various sizes. Addition of the apolipoprotein fractions (especially Fractions II and IV) to sonicated dispersion of sphingomyelin resulted in a pronounced formation of discs which showed a high tendency towards stack formation. Mixtures of Fraction II and lecithin or sphingomyelin were effective in the release of cellular cholesterol from multilayers of aortic smooth muscle cells in culture. These results show the feasibility of net removal of cholesterol from cells which grow in a form resembling a tissue and thus provide a model to study the role of apolipoprotein-phospholipid mixtures in cholesterol removal from cells and tissues in vivo."} {"id": "PMID:164236", "title": "A method for the quantitative determination of glycerolipids containing O-alkyl and O-alk-1-enyl moieties.", "content": "We have developed a spectrophotometric procedure, based on a combination of established methods, for the quantitative determination of aklyl and alk-1-enyl (plasmalogens) ether-linked glycerolipids. It depends upon the release of alkylglycerols and alk-1-enylglycerols from phospholipids by phosphlipase C (Bacillus cereus) followed by saponification or by Vitride reduction the phospholipids; aldehydes are subsequently formed and measured colorimetrically after reacting them with a fuchsin reagent. The total alkyl and alk-1-enyl content of glycerolipids is determined oxidation of the sample withperiodate to form aldehydes and alkylglycolic aldehydes. The O-alk-1-enyl lipid content is determined on a separate sample by measuring the aldehydes produced after acid hydrolysis. The quantity of O-alkyl lipids is calculated from the difference between the values obtained for the total ether-lipid content and that of the O-alk-1enyl lipid content. Alternately, direct determination of alk-1-enylglycerols and alkylglycerols can be made if these hydrolytic products are first separated by thin-layer chromatography.", "contents": "A method for the quantitative determination of glycerolipids containing O-alkyl and O-alk-1-enyl moieties. We have developed a spectrophotometric procedure, based on a combination of established methods, for the quantitative determination of aklyl and alk-1-enyl (plasmalogens) ether-linked glycerolipids. It depends upon the release of alkylglycerols and alk-1-enylglycerols from phospholipids by phosphlipase C (Bacillus cereus) followed by saponification or by Vitride reduction the phospholipids; aldehydes are subsequently formed and measured colorimetrically after reacting them with a fuchsin reagent. The total alkyl and alk-1-enyl content of glycerolipids is determined oxidation of the sample withperiodate to form aldehydes and alkylglycolic aldehydes. The O-alk-1-enyl lipid content is determined on a separate sample by measuring the aldehydes produced after acid hydrolysis. The quantity of O-alkyl lipids is calculated from the difference between the values obtained for the total ether-lipid content and that of the O-alk-1enyl lipid content. Alternately, direct determination of alk-1-enylglycerols and alkylglycerols can be made if these hydrolytic products are first separated by thin-layer chromatography."} {"id": "PMID:164237", "title": "NMR studies of pig low- and high-density serum lipoproteins. Molecular motions and morphology.", "content": "1. NMR spectra of porcine high- and low density lipoproteins (d 1.120--1.210 and 1.019--1.070, respectively) and their extracted lipids were obtained as functions of temperature, frequency and solution viscosity, and from solutions to which paramagnetic species had been added. 2. About one-third of the N(CH3)3 groups in low-density lipoproteins are so immobile that they do not give a sharp resonance at any temperature up to 65 degrees C, unless the particles are disrupted with sodium dodecylsulphate. Most of the protein residues also undergo little segmental motion. 3. A marked restriction of motion of acyl chain terminal CH3 groups suggests that chain interdigitation occurs in low-density lipoprotein. Apart from this, there is a general ordering of the lipids without a decrease in the rate of rotation about bonds, suggesting that the protein organizes the lipids by controlling the molecular packing rather than by direct strong interactions. The lipids are more ordered in low-density than in high-density lipoprotein. 4. All phospholipids with mobile N(CH3)3 groups are at the particle surfaces, in patches separated by protein. In low-density lipoprotein the patches are raised proud of the protein, whereas in high-density lipoproteins the protein and lipid polar groups are coplanar. 5. The high-density lipoprotein results are consistent with literature models for the structure. The low-density lipoprotein results suggest a new model, which is basically a trilayer. The centre consists of a monolayer of phospholipid with tightly-packed polar groups in contact with a protein core. The outer monolayer of phospholipid contains the rest (most) of the protein; the central layer contains the neutral lipid (cholesterol esters and triglycerides), interdigitated into both the inner and outer monolayers. Unesterified cholesterol is distributed through all three layers.", "contents": "NMR studies of pig low- and high-density serum lipoproteins. Molecular motions and morphology. 1. NMR spectra of porcine high- and low density lipoproteins (d 1.120--1.210 and 1.019--1.070, respectively) and their extracted lipids were obtained as functions of temperature, frequency and solution viscosity, and from solutions to which paramagnetic species had been added. 2. About one-third of the N(CH3)3 groups in low-density lipoproteins are so immobile that they do not give a sharp resonance at any temperature up to 65 degrees C, unless the particles are disrupted with sodium dodecylsulphate. Most of the protein residues also undergo little segmental motion. 3. A marked restriction of motion of acyl chain terminal CH3 groups suggests that chain interdigitation occurs in low-density lipoprotein. Apart from this, there is a general ordering of the lipids without a decrease in the rate of rotation about bonds, suggesting that the protein organizes the lipids by controlling the molecular packing rather than by direct strong interactions. The lipids are more ordered in low-density than in high-density lipoprotein. 4. All phospholipids with mobile N(CH3)3 groups are at the particle surfaces, in patches separated by protein. In low-density lipoprotein the patches are raised proud of the protein, whereas in high-density lipoproteins the protein and lipid polar groups are coplanar. 5. The high-density lipoprotein results are consistent with literature models for the structure. The low-density lipoprotein results suggest a new model, which is basically a trilayer. The centre consists of a monolayer of phospholipid with tightly-packed polar groups in contact with a protein core. The outer monolayer of phospholipid contains the rest (most) of the protein; the central layer contains the neutral lipid (cholesterol esters and triglycerides), interdigitated into both the inner and outer monolayers. Unesterified cholesterol is distributed through all three layers."} {"id": "PMID:164238", "title": "Localization of enzymes involved in polyphosphoinositids metabolism on the cytoplasmic surface of the human erythrocyte membrane.", "content": "1. Impermeable inside-out and right-side-out vesicles were prepared from membranes of human erythrocytes. During preparation of each kind of impermeable vesicle, permeable vesicles were also obtained. 2. Incubation of vesicles with [gamma-32P]ATP at 37 degrees C for periods of up to 1 hr did not change the topography or the permeability of the vesicles. 3. Vesicles incorporated labeled phosphate from [gamma-32P]ATP into both diphosphoinositide and triphosphoinositide, but impermeable inside-out vesicles incorporated significantly more nuclide than did right-side-out vesicles. 4. Permeable vesicles derived during the preparation of inside-out vesicles were as active as impermeable inside-out vesicles in the incorporation of labeled phosphate into the polyphosphoinositides. However, permeable vesicles derived during the preparation of right-side out vesicles were not as active. 5. Impermeable right-side-out vesicles, treated with 0.01 percent saponin, incorporated labeled phosphate into the polyphosphoinositides at a level comparable to that of impermeable inside-out vesicles. 6. These data show that the enzymes involved in metabolism of diphosphoinositide and triphosphoinositide are located on the cytoplasmic surface of the erythrocyte membrane.", "contents": "Localization of enzymes involved in polyphosphoinositids metabolism on the cytoplasmic surface of the human erythrocyte membrane. 1. Impermeable inside-out and right-side-out vesicles were prepared from membranes of human erythrocytes. During preparation of each kind of impermeable vesicle, permeable vesicles were also obtained. 2. Incubation of vesicles with [gamma-32P]ATP at 37 degrees C for periods of up to 1 hr did not change the topography or the permeability of the vesicles. 3. Vesicles incorporated labeled phosphate from [gamma-32P]ATP into both diphosphoinositide and triphosphoinositide, but impermeable inside-out vesicles incorporated significantly more nuclide than did right-side-out vesicles. 4. Permeable vesicles derived during the preparation of inside-out vesicles were as active as impermeable inside-out vesicles in the incorporation of labeled phosphate into the polyphosphoinositides. However, permeable vesicles derived during the preparation of right-side out vesicles were not as active. 5. Impermeable right-side-out vesicles, treated with 0.01 percent saponin, incorporated labeled phosphate into the polyphosphoinositides at a level comparable to that of impermeable inside-out vesicles. 6. These data show that the enzymes involved in metabolism of diphosphoinositide and triphosphoinositide are located on the cytoplasmic surface of the erythrocyte membrane."} {"id": "PMID:164239", "title": "Changes in phosoholipid susceptibility toward phospholipases induced by ATP depletion in avian and amphibian erythrocyte membranes.", "content": "About half of the sphingomyelin content of fresh and ATP-depleted chicken erythrocytes is hydrolysed by sphingomyelinase. Removal of spingomyelin exposes the rest of the membrane phospholipids to hydrolysis by phospholipase C only in ATP-depleted but not in fresh cells. Addition of both sphinogomyelinase and phospholipase C to ATP-depleted cells causes about 60-70 percent hydrolysis of the total phospholipids accompanied by extensive (90 percent) hemolysis. The phospholipids of toad erythrocytes are partially available to phospholipase C activity in fresh cells (17-25 percent hydrolysis) without prior sphingomyelinase treatment. However, in ATP-depleted toad cells phospholipase C hydrolyses 66 percent of phospholipids and causes extensive lysis. Treatment of either fresh or ATP-depleted toad erythrocytes by sphingomyelinase together with phospholipase C induces hydrolysis of most of the phospholipds with complete lysis. Restoration of ATP to ATP-depleted cells endows them with resistance to the attack of phospholipase C. The correlation between changes in ATP level and membrane organization as revealed by increased susceptibility toward phospholipases is discussed.", "contents": "Changes in phosoholipid susceptibility toward phospholipases induced by ATP depletion in avian and amphibian erythrocyte membranes. About half of the sphingomyelin content of fresh and ATP-depleted chicken erythrocytes is hydrolysed by sphingomyelinase. Removal of spingomyelin exposes the rest of the membrane phospholipids to hydrolysis by phospholipase C only in ATP-depleted but not in fresh cells. Addition of both sphinogomyelinase and phospholipase C to ATP-depleted cells causes about 60-70 percent hydrolysis of the total phospholipids accompanied by extensive (90 percent) hemolysis. The phospholipids of toad erythrocytes are partially available to phospholipase C activity in fresh cells (17-25 percent hydrolysis) without prior sphingomyelinase treatment. However, in ATP-depleted toad cells phospholipase C hydrolyses 66 percent of phospholipids and causes extensive lysis. Treatment of either fresh or ATP-depleted toad erythrocytes by sphingomyelinase together with phospholipase C induces hydrolysis of most of the phospholipds with complete lysis. Restoration of ATP to ATP-depleted cells endows them with resistance to the attack of phospholipase C. The correlation between changes in ATP level and membrane organization as revealed by increased susceptibility toward phospholipases is discussed."} {"id": "PMID:164240", "title": "Evidence for constrained lipid mobility in the erythrocyte ghost. A spin label study.", "content": "Our data show that the ESR spectrum of 5-nitroxide stearate bound to erythrocyte membranes varies with the amount of label bound and suggest that, at high binding, a significant proportion of label molecules lie within approximately equal to 15-10--8 cm; this gives rise to spin-exchange (ambient temperature) and dipole-dipole interactions. We find that these spectral manifestations due to label clustering can be abolished by reduction of pH and the conjoint action of lysolecithin and trypsin, although both perturbations increase 5-nitroxide stearate binding. Both perturbations are known to mobilize intramembranous particles by modifying or extracting some membrane proteins. We accordingly suggest that the lipids and proteins of erythrocyte membranes exist in a relatively fixed mosaic, and that the mobility of both components is restricted by some membrane-associated protein framework.", "contents": "Evidence for constrained lipid mobility in the erythrocyte ghost. A spin label study. Our data show that the ESR spectrum of 5-nitroxide stearate bound to erythrocyte membranes varies with the amount of label bound and suggest that, at high binding, a significant proportion of label molecules lie within approximately equal to 15-10--8 cm; this gives rise to spin-exchange (ambient temperature) and dipole-dipole interactions. We find that these spectral manifestations due to label clustering can be abolished by reduction of pH and the conjoint action of lysolecithin and trypsin, although both perturbations increase 5-nitroxide stearate binding. Both perturbations are known to mobilize intramembranous particles by modifying or extracting some membrane proteins. We accordingly suggest that the lipids and proteins of erythrocyte membranes exist in a relatively fixed mosaic, and that the mobility of both components is restricted by some membrane-associated protein framework."} {"id": "PMID:164241", "title": "ESR spectral analysis of the molecular motion of spin labels in lipid bilayers and membranes based on a model in terms of two angular motional parameters and rotational correlation times.", "content": "Electron spin resonance (ESR) spectral line shapes are calculated for a nitroxide spin-labeled molecule undergoing rapid restricted rotations (twisting) about its long molecular axis while simultaneously tumbling within a cone. Explicit expressions are derived for the hyperfine splittings and g-values, as well as for the secular contributions to the motionally modulated linewidths. The present model is useful for analyzing the restricted twisting and tumbling motions, and rotational correlation times, of spin-labeled molecules in bilayers. Simulated spectra compare well with experimental spectra of lecithin bilayers marked with cholestane spin label, over a wide temperature range.", "contents": "ESR spectral analysis of the molecular motion of spin labels in lipid bilayers and membranes based on a model in terms of two angular motional parameters and rotational correlation times. Electron spin resonance (ESR) spectral line shapes are calculated for a nitroxide spin-labeled molecule undergoing rapid restricted rotations (twisting) about its long molecular axis while simultaneously tumbling within a cone. Explicit expressions are derived for the hyperfine splittings and g-values, as well as for the secular contributions to the motionally modulated linewidths. The present model is useful for analyzing the restricted twisting and tumbling motions, and rotational correlation times, of spin-labeled molecules in bilayers. Simulated spectra compare well with experimental spectra of lecithin bilayers marked with cholestane spin label, over a wide temperature range."} {"id": "PMID:164242", "title": "Organization of enzymes of glycolysis and of glutathione metabolism in human red cell membranes.", "content": "1) The activities of 16 enzymes of glycolysis and of glutathione metabolism were determined in intact human red cell membranes (ghosts) which were prepared by hypotonic hemolysis. 2) Enzymes and hemoglobin of the ghosts were resolved by two toluene extractions. Only the four enzymes hexokinase, fructose-bisphosphate aldolase, glyceraldehyde-phosphate dehydrogenase and pyruvate kinase could not be released completely from the ghosts. 3) The residual membrane fraction, which was obtained after the toluene extraction of ghosts prepared at 30 imOsM, contained 0.02% of the original hemoglobin content of the red cell. Between 6.5 and 23% of the hemolysate activities of glyceraldehyde-phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase and fructose-bisphosphate aldolase were detected in this fraction after mechanical disruption. 4) Sonication of intact ghosts increased the activities of fructose-bisphosphate aldolase, pyruvate kinase and phosphoglycerate kinase. 5) In \"white\" ghosts prepared at 5 imOsM phosphate buffer which contained 0.5% of the original hemoglobin the activities of fructose-bisphosphate aldolase and glyceraldehyde-phosphate dehydrogenase were detected at high levels. The activities of pyruvate kinase and phosphoglycerate kinase were low in these preparations. 6) The results indicate that one part of all enzymes is loosely attached to the inner surface of the membrane as is hemoglobin. A second part, the \"cryptic enzyme activity\", is available after resolving by toluene. A residual part of four enzymes is firmly bound to the membrane. Two of them (fructose-bisphosphate aldolase and glyceraldehyde-phosphate dehydrogenase) are oriented toward the inner surface of the membrane, whereas pyruvate kinase and phosphoglycerate kinase are hidden in the lipid core of the membrane.", "contents": "Organization of enzymes of glycolysis and of glutathione metabolism in human red cell membranes. 1) The activities of 16 enzymes of glycolysis and of glutathione metabolism were determined in intact human red cell membranes (ghosts) which were prepared by hypotonic hemolysis. 2) Enzymes and hemoglobin of the ghosts were resolved by two toluene extractions. Only the four enzymes hexokinase, fructose-bisphosphate aldolase, glyceraldehyde-phosphate dehydrogenase and pyruvate kinase could not be released completely from the ghosts. 3) The residual membrane fraction, which was obtained after the toluene extraction of ghosts prepared at 30 imOsM, contained 0.02% of the original hemoglobin content of the red cell. Between 6.5 and 23% of the hemolysate activities of glyceraldehyde-phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase and fructose-bisphosphate aldolase were detected in this fraction after mechanical disruption. 4) Sonication of intact ghosts increased the activities of fructose-bisphosphate aldolase, pyruvate kinase and phosphoglycerate kinase. 5) In \"white\" ghosts prepared at 5 imOsM phosphate buffer which contained 0.5% of the original hemoglobin the activities of fructose-bisphosphate aldolase and glyceraldehyde-phosphate dehydrogenase were detected at high levels. The activities of pyruvate kinase and phosphoglycerate kinase were low in these preparations. 6) The results indicate that one part of all enzymes is loosely attached to the inner surface of the membrane as is hemoglobin. A second part, the \"cryptic enzyme activity\", is available after resolving by toluene. A residual part of four enzymes is firmly bound to the membrane. Two of them (fructose-bisphosphate aldolase and glyceraldehyde-phosphate dehydrogenase) are oriented toward the inner surface of the membrane, whereas pyruvate kinase and phosphoglycerate kinase are hidden in the lipid core of the membrane."} {"id": "PMID:164243", "title": "Solubilized DNA-dependent nuclear RNA polymerases from the mammary glands of late-pregnant rats.", "content": "Mammary gland nuclear extracts from late-pregnant Wistar or Sprague-Dwaley rats, analyzed by DEAE-Sephadex chromatography, were found to contain DNA-dependent RNA polymerases, cyclic nucleotide-binding proteins, and cyclic AMP-independent protein kinases. 1. The fractions from chromatographed nuclear extracts which contained nucleolar enzymes or nucleoplasmic enzyme II, bound radioactive cyclic AMP and cyclic GMP. Other fractions also bound cyclic nucleotides, some preferentially associating with one or the other compound. 2. Cyclic AMP increased the amount of RNA formed by several alpha-amanitin-insensitive fractions containing nucleolar enzymes. 3. Cyclic AMP reduced the amount of RNA formed by column fractions which included nucleoplasmic enzyme II. 4. Cyclic GMP increased the amount of RNA synthesized by column fractions containing enzyme II. 5. Two major cyclic AMP-independent protein kinases which did not elute with enzymes Ib and II, and several minor protein kinases were present. These findings may have important implications for understanding the proximate control of transcription. A relationship between them is not established, but is under study.", "contents": "Solubilized DNA-dependent nuclear RNA polymerases from the mammary glands of late-pregnant rats. Mammary gland nuclear extracts from late-pregnant Wistar or Sprague-Dwaley rats, analyzed by DEAE-Sephadex chromatography, were found to contain DNA-dependent RNA polymerases, cyclic nucleotide-binding proteins, and cyclic AMP-independent protein kinases. 1. The fractions from chromatographed nuclear extracts which contained nucleolar enzymes or nucleoplasmic enzyme II, bound radioactive cyclic AMP and cyclic GMP. Other fractions also bound cyclic nucleotides, some preferentially associating with one or the other compound. 2. Cyclic AMP increased the amount of RNA formed by several alpha-amanitin-insensitive fractions containing nucleolar enzymes. 3. Cyclic AMP reduced the amount of RNA formed by column fractions which included nucleoplasmic enzyme II. 4. Cyclic GMP increased the amount of RNA synthesized by column fractions containing enzyme II. 5. Two major cyclic AMP-independent protein kinases which did not elute with enzymes Ib and II, and several minor protein kinases were present. These findings may have important implications for understanding the proximate control of transcription. A relationship between them is not established, but is under study."} {"id": "PMID:164244", "title": "Mitochondrial protein synthesis and the stimulation of steroidogenesis by cyclic adenosine 3',5'-monophosphate in isolated rat adrenal cells.", "content": "The stimulation by cyclic AMP of steroidogenesis in rat adrenal cells isolated by trypsin treatment was inhibited by D-threo-chloramphenicol and by its L-threo-isomer. The former is an inhibitor of mitochondrial protein synthesis while the latter is not. Both substances, at concentrations which inhibit steroidogenesis, inhibit amino acid incorporation into the proteins of microsomes. Inhibition in other subcellular fractions also occurs depending on the isomer and its concentration. In no case was there a preferential inhibition of amino acid incorporation into mitochondrial proteins. Carbomycin, another inhibitor of mitochondrial protein synthesis, gave similar results. In addition, subfractionation of mitochondria in these experiments revealed no preferential inhibition of amino acid incorporation into the proteins of either the soluble of membrane fractions of this organelle. The above results were obtained at several concentrations of the inhibitors when only partial inhibition of steroidogenesis was present. Both isomers of chloramphenicol inhibited steroidogenesis in a cell-free system to an extent equal to that found with cyclic AMP-stimulated steroidogenesis in intact cells. It is concluded that these inhibitors of mitochondrial protein synthesis have multiple metabolic effects in adrenal cells.", "contents": "Mitochondrial protein synthesis and the stimulation of steroidogenesis by cyclic adenosine 3',5'-monophosphate in isolated rat adrenal cells. The stimulation by cyclic AMP of steroidogenesis in rat adrenal cells isolated by trypsin treatment was inhibited by D-threo-chloramphenicol and by its L-threo-isomer. The former is an inhibitor of mitochondrial protein synthesis while the latter is not. Both substances, at concentrations which inhibit steroidogenesis, inhibit amino acid incorporation into the proteins of microsomes. Inhibition in other subcellular fractions also occurs depending on the isomer and its concentration. In no case was there a preferential inhibition of amino acid incorporation into mitochondrial proteins. Carbomycin, another inhibitor of mitochondrial protein synthesis, gave similar results. In addition, subfractionation of mitochondria in these experiments revealed no preferential inhibition of amino acid incorporation into the proteins of either the soluble of membrane fractions of this organelle. The above results were obtained at several concentrations of the inhibitors when only partial inhibition of steroidogenesis was present. Both isomers of chloramphenicol inhibited steroidogenesis in a cell-free system to an extent equal to that found with cyclic AMP-stimulated steroidogenesis in intact cells. It is concluded that these inhibitors of mitochondrial protein synthesis have multiple metabolic effects in adrenal cells."} {"id": "PMID:164245", "title": "Alterations in SVT2 cell transfer RNAs in response to cell density and serum type.", "content": "The chromatographic elution profiles of tRNA-A sn, tRNA-A sp, tRNA-H is and tRNA-T y r from SV40-transformed BALB-3T3 cells grown in fetal calf serum or cald serum-supplemented media have been examined. The relative proportions of certain of the isoaccepting species of these four tRNAs are altered in a similar fashion depending on the serum type. It is suggested that the elution profile alterations reflect the extent of modifications of a specific G residue to the minor nucleoside Q, and that this process differs between untransformed and transformed cells. In addition, cell density appears to influence the Q content of these tRNAs, though other density-dependent tRNA modifications also appear to occur.", "contents": "Alterations in SVT2 cell transfer RNAs in response to cell density and serum type. The chromatographic elution profiles of tRNA-A sn, tRNA-A sp, tRNA-H is and tRNA-T y r from SV40-transformed BALB-3T3 cells grown in fetal calf serum or cald serum-supplemented media have been examined. The relative proportions of certain of the isoaccepting species of these four tRNAs are altered in a similar fashion depending on the serum type. It is suggested that the elution profile alterations reflect the extent of modifications of a specific G residue to the minor nucleoside Q, and that this process differs between untransformed and transformed cells. In addition, cell density appears to influence the Q content of these tRNAs, though other density-dependent tRNA modifications also appear to occur."} {"id": "PMID:164252", "title": "Influence of reserpine on all-night sleep pattern in nonlobotomized and lobotomized chronic schizophrenic patients.", "content": "This study was performed on two groups of schizophrenic patients. One group consisted on nine nonlobotomized patients and the other of nine lobotomized ones. The groups were matched for age, sex, duration of illness, clinical symptoms, type and dose of psychopharmacological treatment. The patients of both groups were administered 1 mg of reserpine half an hour before bedtime, for three successive days. Before reserpine administration the mean percentage time of the NREM stage 4 was significantly higher in the lobotomized group. There was no significant difference in the REM parameters. After three days of reserpine administration in the nonlobotomized group, there was no significant difference in the mean percentage of the NREM stage 4, whereas the mean REM percentage significantly increased and REM latency decreased. In the lobotomized group the same procedure, i.e., three days of reserpine administration, provoked a significant decrease in the mean percentage of the NREM stage 4 and no significant changes in the REM parameters. This difference in reserpine action on sleep in the lobotomized group is discussed.", "contents": "Influence of reserpine on all-night sleep pattern in nonlobotomized and lobotomized chronic schizophrenic patients. This study was performed on two groups of schizophrenic patients. One group consisted on nine nonlobotomized patients and the other of nine lobotomized ones. The groups were matched for age, sex, duration of illness, clinical symptoms, type and dose of psychopharmacological treatment. The patients of both groups were administered 1 mg of reserpine half an hour before bedtime, for three successive days. Before reserpine administration the mean percentage time of the NREM stage 4 was significantly higher in the lobotomized group. There was no significant difference in the REM parameters. After three days of reserpine administration in the nonlobotomized group, there was no significant difference in the mean percentage of the NREM stage 4, whereas the mean REM percentage significantly increased and REM latency decreased. In the lobotomized group the same procedure, i.e., three days of reserpine administration, provoked a significant decrease in the mean percentage of the NREM stage 4 and no significant changes in the REM parameters. This difference in reserpine action on sleep in the lobotomized group is discussed."} {"id": "PMID:164253", "title": "The behavioral effects of L-methionine and related compounds in rats and mice.", "content": "Several groups of investigators have reported that the administration of L-methionine, with or without a monoamine oxidase inhibitor, induced an acute florid psychotic reaction in 40 percent of schizophrenics tested. The mode of action of L-methionine in brain is unknown, but may be via one or more of three mechanisms: the excess methionine (i) may lead to the production by transmethylation of some psychotomimetic methylated derivative of dopamine or serotonin, or (ii) could result in an increase in the levels of a metabolite of methionine (e.g., homocysteine, cystathionine, or cysteine), or (iii) may effect the cellular uptake of other amino acids. In order to test the first two hypotheses, L-methionine, betaine (another metyl group donor), L-methionine plus L-serine, L-cysteine, L-serine, and saline (as a control) were studied on the sleep-wake cycles of random-bred Swiss mice and on the avoidance behavior or rats. L-methionine plus L-histidine, L-methionine plus nicotinamide, L-histidine, and nicotinamide were also tested in the mice. Daily injections of 250 mg/kg of these compounds were administered for at least 21 consecutive days. Schedule performance in the rat and the sleep-wake cycles of the mice were monitored during this period and compared to controls. L-Methionine induced behavioral and sleep cycle disturbances which were removed by the simultaneous administration of L-serine but not by the addition of L-histidine or nicotinamide. These data suggest that the disruption may be due to an increase in the levels of one of the metabolities of methionine, homocysteine, rather than to an increase in the number of available methyl groups.", "contents": "The behavioral effects of L-methionine and related compounds in rats and mice. Several groups of investigators have reported that the administration of L-methionine, with or without a monoamine oxidase inhibitor, induced an acute florid psychotic reaction in 40 percent of schizophrenics tested. The mode of action of L-methionine in brain is unknown, but may be via one or more of three mechanisms: the excess methionine (i) may lead to the production by transmethylation of some psychotomimetic methylated derivative of dopamine or serotonin, or (ii) could result in an increase in the levels of a metabolite of methionine (e.g., homocysteine, cystathionine, or cysteine), or (iii) may effect the cellular uptake of other amino acids. In order to test the first two hypotheses, L-methionine, betaine (another metyl group donor), L-methionine plus L-serine, L-cysteine, L-serine, and saline (as a control) were studied on the sleep-wake cycles of random-bred Swiss mice and on the avoidance behavior or rats. L-methionine plus L-histidine, L-methionine plus nicotinamide, L-histidine, and nicotinamide were also tested in the mice. Daily injections of 250 mg/kg of these compounds were administered for at least 21 consecutive days. Schedule performance in the rat and the sleep-wake cycles of the mice were monitored during this period and compared to controls. L-Methionine induced behavioral and sleep cycle disturbances which were removed by the simultaneous administration of L-serine but not by the addition of L-histidine or nicotinamide. These data suggest that the disruption may be due to an increase in the levels of one of the metabolities of methionine, homocysteine, rather than to an increase in the number of available methyl groups."} {"id": "PMID:164257", "title": "Somatosensory cerebral evoked potentials after vascular lesions of the brain-stem and diencephalon.", "content": "Clinical and electrophysiological observations are described in 7 patients with clinically well-identified vascular lesions of the brain-stem or diencephalon. In the patients of Group A with a thalamic syndrome, the somatosensory cerebral evoked potentials had a reduced voltage and increased latency on the affected side. No significant anomalies were recorded in the patients of Group B with a Wallenberg or Weber syndrome. In patients of group C with a locked-in syndrome, the cerebral evoked potentials presented marked bilateral anomalies which provided interesting data about the extension of the pontine vascular lesions into the tegmentum. The pathophysiological mechanisms involved in the changes of average cerebral evoked potentials and in the slowing of corticipetal conduction are discussed.", "contents": "Somatosensory cerebral evoked potentials after vascular lesions of the brain-stem and diencephalon. Clinical and electrophysiological observations are described in 7 patients with clinically well-identified vascular lesions of the brain-stem or diencephalon. In the patients of Group A with a thalamic syndrome, the somatosensory cerebral evoked potentials had a reduced voltage and increased latency on the affected side. No significant anomalies were recorded in the patients of Group B with a Wallenberg or Weber syndrome. In patients of group C with a locked-in syndrome, the cerebral evoked potentials presented marked bilateral anomalies which provided interesting data about the extension of the pontine vascular lesions into the tegmentum. The pathophysiological mechanisms involved in the changes of average cerebral evoked potentials and in the slowing of corticipetal conduction are discussed."} {"id": "PMID:164259", "title": "Physiological studies of the dying-back phenomenon. Muscle stretch afferents in acrylamide neuropathy.", "content": "(1) The responses of 1,001 medial gastrocnemius afferents with conduction velocities of 24-126 m/sec have been studied in cats with experimental acrylamide neuropathy. (2) Many units which conducted at velocities indicating that they innervated muscle stretch receptors failed to discharge during muscle stretch or contraction. In animals with mild neuropathy 10 per cent of 366 units were non-responsive. In animals with moderate or severe neuropathy the proportion of non-responsive units was 68 per cent of 315 fibres and 89 per cent of 320 fibres respectively. Group I fibres were involved to a greater extent than Group II fibres. (3) The distributions of identified functioning units with respect to conduction velocity were normal, indicating that acrylamide did not produce conduction slowing before failure of function. (4) Electrophysiological and histological findings indicate that acrylamide initially produces failure of impluse conduction and subsequent fibre breakdown in the terminal axon while normal impulse conduction is preserved more proximally.", "contents": "Physiological studies of the dying-back phenomenon. Muscle stretch afferents in acrylamide neuropathy. (1) The responses of 1,001 medial gastrocnemius afferents with conduction velocities of 24-126 m/sec have been studied in cats with experimental acrylamide neuropathy. (2) Many units which conducted at velocities indicating that they innervated muscle stretch receptors failed to discharge during muscle stretch or contraction. In animals with mild neuropathy 10 per cent of 366 units were non-responsive. In animals with moderate or severe neuropathy the proportion of non-responsive units was 68 per cent of 315 fibres and 89 per cent of 320 fibres respectively. Group I fibres were involved to a greater extent than Group II fibres. (3) The distributions of identified functioning units with respect to conduction velocity were normal, indicating that acrylamide did not produce conduction slowing before failure of function. (4) Electrophysiological and histological findings indicate that acrylamide initially produces failure of impluse conduction and subsequent fibre breakdown in the terminal axon while normal impulse conduction is preserved more proximally."} {"id": "PMID:164260", "title": "Proteins of rat brain myelin in neonatal hypothyroidism.", "content": "The amount of myelin and its protein composition was studied in hypothyroid rats during the first 30 days after birth. Although the brain weight was 92% of that in the controls, the yield of myelin in hypothyroid animals was only 60% of that in controls. The protein and glycoprotein ocmposition of the isolated myelin was similar in hypothyroid and control rats. The 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity in whole brain from hypothyroid animals was only 60% of the controls and reflected the decrease in myelin formation. In isolated myelin the specific activity of CNP was not different in hypothyroid and control animals with the exception of very immature animals (10 days). The major fucose-labeled glycoprotein in myelin of the hypothyroid rats had a slightly higher apparent molecular weight than that in myelin from age matched controls, probably reflecting a retardation of brain maturation and myelin formation.", "contents": "Proteins of rat brain myelin in neonatal hypothyroidism. The amount of myelin and its protein composition was studied in hypothyroid rats during the first 30 days after birth. Although the brain weight was 92% of that in the controls, the yield of myelin in hypothyroid animals was only 60% of that in controls. The protein and glycoprotein ocmposition of the isolated myelin was similar in hypothyroid and control rats. The 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity in whole brain from hypothyroid animals was only 60% of the controls and reflected the decrease in myelin formation. In isolated myelin the specific activity of CNP was not different in hypothyroid and control animals with the exception of very immature animals (10 days). The major fucose-labeled glycoprotein in myelin of the hypothyroid rats had a slightly higher apparent molecular weight than that in myelin from age matched controls, probably reflecting a retardation of brain maturation and myelin formation."} {"id": "PMID:164261", "title": "Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section.", "content": "Chemical properties of substance P in the spinal cord and dorsal roots of the cat were examined by gel chromatography and paper electrophoresis. The results suggest that the substance is identical with the undecapeptide, hypothalamic substance P, recently isolated from bovine hypothalamus. Distribution of substance P in the cat spinal cord (L5-S1) was investigated. Substance P was highly concentrated in the dorsal horn, where the highest level was found in the dorsal part. After the unilateral ligation and/or section of the dorsal roots, the level of substance P in the dorsal horn, particularly in its dorsal part, was markedly lowered. In the ligated and sectioned dorsal root, substance P was highly accumulated on the ganglion side, whereas its level was lowered on the central side of the ligature. These results suggest that hypothalamic substance P synthesized in the spinal ganglia is transported in the dorsal root toward their intraspinal axon terminals, where the substance is concentrated and serves as a neurotransmitter.", "contents": "Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section. Chemical properties of substance P in the spinal cord and dorsal roots of the cat were examined by gel chromatography and paper electrophoresis. The results suggest that the substance is identical with the undecapeptide, hypothalamic substance P, recently isolated from bovine hypothalamus. Distribution of substance P in the cat spinal cord (L5-S1) was investigated. Substance P was highly concentrated in the dorsal horn, where the highest level was found in the dorsal part. After the unilateral ligation and/or section of the dorsal roots, the level of substance P in the dorsal horn, particularly in its dorsal part, was markedly lowered. In the ligated and sectioned dorsal root, substance P was highly accumulated on the ganglion side, whereas its level was lowered on the central side of the ligature. These results suggest that hypothalamic substance P synthesized in the spinal ganglia is transported in the dorsal root toward their intraspinal axon terminals, where the substance is concentrated and serves as a neurotransmitter."} {"id": "PMID:164265", "title": "Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats.", "content": "We measured simultaneously the oxidative metabolic activity, monitored as the tissue fluorescence attribute to intramitochondrial NADH, the extracellular potassium level with ion-selective microelectrodes, and the focal extracellular electrical potential, of one site in intact cerebral cortex of cats. When the cerebral was stimulated by trains of repeated electric pulses applied either directly to its surface or to an afferent pathway, the corrected cortical fluorescence (F-R) declined indicating oxidation of NADH, the activity of extracellular potassium [K+]o increased, and the extracellular potential (Vec) shifted in the negative direction. When mild to moderate stimuli not exceeding 10-15 sec in duration were used, a 3-fold correlation was found between these three variables. The regression of F-R over either Vec, or over log [K+]o had a positive ordinal intercept. The results are in agreement with earlier suggestions 4,24,25,43,45,46 that (a) much but not all the oxidative metabolic response of cortex to electrical stimulation is expended in restoring disturbed ion balance; and (b) that sustained shifts of potential (SP) in response to repetitive electrical stimulation are generated by glia cells depolarized by excess potassium. The magnitude of SP shifts associated with a given elevation of [k+]o are smaller in cerebral cortex than in spinal cord48,49. The correlation of F-R with [K+]o breaks down when pathologic processes of either seizure activity or spreading depression set in. During paroxysmal activity [K+]o tends to remain confined below 10-12 mM, a level observed in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing tissue. This observation is hard to reconcile with the suggestion that excess potassium is a factor in the generation of seizures, at least of the type observed in this study. When [K+]o levels exceeded 10-12 mM, spreading depression invariably followed at least under the unanesthetized condition in these experiments. During spreading depression [K+]o levels rose to exceed 30 mM, sometimes 80 mM. NADH was oxidized during spreading depression to a level comparable to that seen in seizures. The observations are compatible with the suggestion13 that spreading depression occurs whenever the release of potassium into extracellular fluid is overloading its clearance therefrom.", "contents": "Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. We measured simultaneously the oxidative metabolic activity, monitored as the tissue fluorescence attribute to intramitochondrial NADH, the extracellular potassium level with ion-selective microelectrodes, and the focal extracellular electrical potential, of one site in intact cerebral cortex of cats. When the cerebral was stimulated by trains of repeated electric pulses applied either directly to its surface or to an afferent pathway, the corrected cortical fluorescence (F-R) declined indicating oxidation of NADH, the activity of extracellular potassium [K+]o increased, and the extracellular potential (Vec) shifted in the negative direction. When mild to moderate stimuli not exceeding 10-15 sec in duration were used, a 3-fold correlation was found between these three variables. The regression of F-R over either Vec, or over log [K+]o had a positive ordinal intercept. The results are in agreement with earlier suggestions 4,24,25,43,45,46 that (a) much but not all the oxidative metabolic response of cortex to electrical stimulation is expended in restoring disturbed ion balance; and (b) that sustained shifts of potential (SP) in response to repetitive electrical stimulation are generated by glia cells depolarized by excess potassium. The magnitude of SP shifts associated with a given elevation of [k+]o are smaller in cerebral cortex than in spinal cord48,49. The correlation of F-R with [K+]o breaks down when pathologic processes of either seizure activity or spreading depression set in. During paroxysmal activity [K+]o tends to remain confined below 10-12 mM, a level observed in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing tissue. This observation is hard to reconcile with the suggestion that excess potassium is a factor in the generation of seizures, at least of the type observed in this study. When [K+]o levels exceeded 10-12 mM, spreading depression invariably followed at least under the unanesthetized condition in these experiments. During spreading depression [K+]o levels rose to exceed 30 mM, sometimes 80 mM. NADH was oxidized during spreading depression to a level comparable to that seen in seizures. The observations are compatible with the suggestion13 that spreading depression occurs whenever the release of potassium into extracellular fluid is overloading its clearance therefrom."} {"id": "PMID:164267", "title": "The specificity of oxidase and kinase preparations from Pseudomonas fluorescens towards deoxyfluoromonosaccharides.", "content": "With partially purified enzyme preparations from cell-free extracts of Pseudomonas fluorescens, 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid are substrates for glucose oxidase (EC 1.1.3.4.) and gluconate dehydrogenase (EC 1.1.99.3), with K-m values 18.2 mM and 11.8 mM, respectively. The same enzymes that oxidize glucose and gluconic acid probably oxidize 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid. The latter fluorinated carbohydrates and the presumed formation of 3-deoxy-3-fluoro-2-keto-D-gluconic acid, which has been isolated as a calcium salt and characterizied, are not substrates for gluconokinase (EC 2.7.1.12). Both 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid act as competitive inhibitors of this enzyme preparation for gluconate, with K-i values 47.5 mM and 14.8 mM, respectively.", "contents": "The specificity of oxidase and kinase preparations from Pseudomonas fluorescens towards deoxyfluoromonosaccharides. With partially purified enzyme preparations from cell-free extracts of Pseudomonas fluorescens, 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid are substrates for glucose oxidase (EC 1.1.3.4.) and gluconate dehydrogenase (EC 1.1.99.3), with K-m values 18.2 mM and 11.8 mM, respectively. The same enzymes that oxidize glucose and gluconic acid probably oxidize 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid. The latter fluorinated carbohydrates and the presumed formation of 3-deoxy-3-fluoro-2-keto-D-gluconic acid, which has been isolated as a calcium salt and characterizied, are not substrates for gluconokinase (EC 2.7.1.12). Both 3-deoxy-3-fluoro-D-glucose and 3-deoxy-3-fluoro-D-gluconic acid act as competitive inhibitors of this enzyme preparation for gluconate, with K-i values 47.5 mM and 14.8 mM, respectively."} {"id": "PMID:164268", "title": "Effects of potassium azide on soil microbial populations and soil enzymatic activities.", "content": "Preplant applications of potassium azide (KN3) to pine nursery beds were evaluated for effect on the soil microflora and on soil enzyme activity where either plastic-sealing or water-sealing techniques were used. Two weeks after incorporation of azide (0-224 kg/hs), soil samplings revealed reduced populations of bacteria and fungi and a corresponding decline in invertase and amylase activities. These effects were proportionate to the amount of azide used and were more pronounced in plastic-sealed plots. Phosphatase activity was little affected. Five weeks after azide application, bacterial populations were higher in treated plots than in controls. Greater numbers of bacteria were recorded from plastic-sealed plots and highest populations coincided with plots receiving the highest rates of azide, regardless of the sealing technique. Fungal populations at this sampling were generally less in treated plots than in the controls, but were higher under plastic seal. At this time, changes in invertase and amylase activities did not correspond to increased microbial numbers. Sixteen weeks after applications of KN3, bacterial populations in treated plots did not differ significantly from controls, but remained higher in plastic-sealed than water-sealed plots. Fungal populations under plastic seal had changed little and remained significantly lower in treated water-sealed plots than in controls. The earlier recorded reduction in invertase and amylase activities was still evident at the final sampling;", "contents": "Effects of potassium azide on soil microbial populations and soil enzymatic activities. Preplant applications of potassium azide (KN3) to pine nursery beds were evaluated for effect on the soil microflora and on soil enzyme activity where either plastic-sealing or water-sealing techniques were used. Two weeks after incorporation of azide (0-224 kg/hs), soil samplings revealed reduced populations of bacteria and fungi and a corresponding decline in invertase and amylase activities. These effects were proportionate to the amount of azide used and were more pronounced in plastic-sealed plots. Phosphatase activity was little affected. Five weeks after azide application, bacterial populations were higher in treated plots than in controls. Greater numbers of bacteria were recorded from plastic-sealed plots and highest populations coincided with plots receiving the highest rates of azide, regardless of the sealing technique. Fungal populations at this sampling were generally less in treated plots than in the controls, but were higher under plastic seal. At this time, changes in invertase and amylase activities did not correspond to increased microbial numbers. Sixteen weeks after applications of KN3, bacterial populations in treated plots did not differ significantly from controls, but remained higher in plastic-sealed than water-sealed plots. Fungal populations under plastic seal had changed little and remained significantly lower in treated water-sealed plots than in controls. The earlier recorded reduction in invertase and amylase activities was still evident at the final sampling;"} {"id": "PMID:164269", "title": "Dissimilation of the lignin model compound veratrylglycerol-beta-(o-methoxyphenyl) ether by Pseudomonas acidovorans: initial transformations.", "content": "The initial transformadomonas acidovorans are demethylation of the 4-methoxyl group of the 3,4-dimethoxyphenyl portion of the molecule, and a NAD+-linked dehydrogenation of the benzyl alcohol group. Based on these findings and those described before, an overall degradation scheme is postulated.", "contents": "Dissimilation of the lignin model compound veratrylglycerol-beta-(o-methoxyphenyl) ether by Pseudomonas acidovorans: initial transformations. The initial transformadomonas acidovorans are demethylation of the 4-methoxyl group of the 3,4-dimethoxyphenyl portion of the molecule, and a NAD+-linked dehydrogenation of the benzyl alcohol group. Based on these findings and those described before, an overall degradation scheme is postulated."} {"id": "PMID:164275", "title": "Glomus jugulare tumors: effects of radiotherapy.", "content": "Twenty glomus jugulare tumors which received x-ray therapy are analyzed. Postirradiation angiography showed persistent tumor vessels and abnormal channels in eight patients. Histologic study of five postirradiation specimens showed that tumor cells persisted after treatment in a significant proportion of the patients. Vascular response was nonuniform and consisted of endothelial hyperplasia and subendothelial hyalinization. Radiotherapy is not always effective in the permanent eradication of the tumor when used as the only modality of treatment in patients with large glomus jugulare tumors. Because of the frequent recurrence after irradiation or surgical resection, a combination of both modalities offers the patient the best probability of cure.", "contents": "Glomus jugulare tumors: effects of radiotherapy. Twenty glomus jugulare tumors which received x-ray therapy are analyzed. Postirradiation angiography showed persistent tumor vessels and abnormal channels in eight patients. Histologic study of five postirradiation specimens showed that tumor cells persisted after treatment in a significant proportion of the patients. Vascular response was nonuniform and consisted of endothelial hyperplasia and subendothelial hyalinization. Radiotherapy is not always effective in the permanent eradication of the tumor when used as the only modality of treatment in patients with large glomus jugulare tumors. Because of the frequent recurrence after irradiation or surgical resection, a combination of both modalities offers the patient the best probability of cure."} {"id": "PMID:164276", "title": "Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases.", "content": "This report describes the clinical and biochemical features of 30 cases of ectopic ACTH-producing tumors diagnosed by the detection of ACTH in the tumor tissues. Several uncommon tumors, such as tumors of the esophagus, stomach, and larynx, were included in this series. None of the patients with bronchogenic carcinoma showed signs of classical Cushing's syndrome, whereas 7 of the remaining 13 patients with other tumors were Cushingoid in appearance. Adrenocortical hyperfunction was present in 61 percent at the first examination and developed during the course of the disease in 18 percent more. In the remaining patients (21 percent), adrenocortical function remained within normal limits. These results indicate that there exist ectopic ACTH-producing tumors without clinical and biochemical sequelae of excess hormone. In some of the tumor extracts studied, MSH and CRF-like activities and serotonin were detected. This suggests that multiple hormone production is not uncommon in ectopic ACTH-producing tumors.", "contents": "Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. This report describes the clinical and biochemical features of 30 cases of ectopic ACTH-producing tumors diagnosed by the detection of ACTH in the tumor tissues. Several uncommon tumors, such as tumors of the esophagus, stomach, and larynx, were included in this series. None of the patients with bronchogenic carcinoma showed signs of classical Cushing's syndrome, whereas 7 of the remaining 13 patients with other tumors were Cushingoid in appearance. Adrenocortical hyperfunction was present in 61 percent at the first examination and developed during the course of the disease in 18 percent more. In the remaining patients (21 percent), adrenocortical function remained within normal limits. These results indicate that there exist ectopic ACTH-producing tumors without clinical and biochemical sequelae of excess hormone. In some of the tumor extracts studied, MSH and CRF-like activities and serotonin were detected. This suggests that multiple hormone production is not uncommon in ectopic ACTH-producing tumors."} {"id": "PMID:164277", "title": "Biochemical characterization of carcinogen-induced mammary hyperplastic aveolar nodule and tumor in the rat.", "content": "Biochemical parameters characterizing growth, functional activity, and hormone dependence were compared in the normal mammary gland, the 7,12-dimethylbenz(a)anthracene-induced hyperplastic aveolar nodule (HAN), and the mammary tumor in the rat. The rate of DNA synthesis in HAN was significantly lower than the rates in either the normal mammary gland cells or the mammary tumor cells cultured in medium containing identical hormone supplement for the same duration of time. The rate of casein synthesis in the explants of pregnant rat mammary gland and HAN was greatly stimulated when cultured in medium containing insulin, cortisol, and prolactin. The mammary tumor, however, failed to produce an increase in casein synthesis under the same experimental conditions. The specific estradiol-binding proteins were either absent or present in very low concentrations in HAN. In contrast, mammary tumor cytosol contained high concentrations of specific estrogen-binding proteins. The normal mammary gland, in spite of its low cellularity, had twice as many estradiol-binding macromolecules as did HAN. Altogether, these results show that HAN cell populations differ from normal mammary gland and mammary tumor cells by their nonresponsiveness to hormonal stimulation for growth and by their lack of specific receptors for extradiol. They retain, however, the functional capacity to synthesize casein, a biochemical property that the mammary tumor does not posses.", "contents": "Biochemical characterization of carcinogen-induced mammary hyperplastic aveolar nodule and tumor in the rat. Biochemical parameters characterizing growth, functional activity, and hormone dependence were compared in the normal mammary gland, the 7,12-dimethylbenz(a)anthracene-induced hyperplastic aveolar nodule (HAN), and the mammary tumor in the rat. The rate of DNA synthesis in HAN was significantly lower than the rates in either the normal mammary gland cells or the mammary tumor cells cultured in medium containing identical hormone supplement for the same duration of time. The rate of casein synthesis in the explants of pregnant rat mammary gland and HAN was greatly stimulated when cultured in medium containing insulin, cortisol, and prolactin. The mammary tumor, however, failed to produce an increase in casein synthesis under the same experimental conditions. The specific estradiol-binding proteins were either absent or present in very low concentrations in HAN. In contrast, mammary tumor cytosol contained high concentrations of specific estrogen-binding proteins. The normal mammary gland, in spite of its low cellularity, had twice as many estradiol-binding macromolecules as did HAN. Altogether, these results show that HAN cell populations differ from normal mammary gland and mammary tumor cells by their nonresponsiveness to hormonal stimulation for growth and by their lack of specific receptors for extradiol. They retain, however, the functional capacity to synthesize casein, a biochemical property that the mammary tumor does not posses."} {"id": "PMID:164278", "title": "S-adenosylmethionine:protein methyltransferases in hepatomas.", "content": "Protein methylase III (S-adenosylmethionine:proteinlysine methyltransferase; ED 2.1.1.25) and protein methylase I (S-adenosylmethionine:protein-arginine methyltransferase; EC 2.1.1.23) activities were examined in isolated nuclei and cytosol fraction, respectively, from various hepatomas with different growth rates. The enzyme activities of both enzymes paralleled the rates of tumor growth in fast- and moderately growing hepatomas. The parallelism was more evident with protein methylase I than with protein methylase III. While protein methylase III activity was elevated in the fast- to moderately growing hepatomas, the enzyme that is responsible for demethylating proteins, epsilon-alkyllysinase (epsilon-slkyl-L-lysine:oxygen oxidoreductase; EC 1.5.3.4), had an inverse relationship to the rate of tumor growth, thus suggesting a possible physiological antagonism. When isolated rat liver nuclei were methylated in vitro with S-adenosyl-L-[methyl-14 C]methionine as methyl donor, H2SO4-insoluble protein and histones had almost equal amounts of methyl-14 C incorporated. However, amino acid analysis revealed that methylated arginines are the predominant form of radioactivity in the H2SO4-insoluble protein (product of protein methylase I), while methylated lysines are the major methylated amino acids in the histones (product of protein methylase III). Furthermore, the hydrolysate of the H2SO4-insoluble protein showed four unknown radioactivity peaks on the amino acid analyzer in addition to the known methylated arginine and lysine derivatives.", "contents": "S-adenosylmethionine:protein methyltransferases in hepatomas. Protein methylase III (S-adenosylmethionine:proteinlysine methyltransferase; ED 2.1.1.25) and protein methylase I (S-adenosylmethionine:protein-arginine methyltransferase; EC 2.1.1.23) activities were examined in isolated nuclei and cytosol fraction, respectively, from various hepatomas with different growth rates. The enzyme activities of both enzymes paralleled the rates of tumor growth in fast- and moderately growing hepatomas. The parallelism was more evident with protein methylase I than with protein methylase III. While protein methylase III activity was elevated in the fast- to moderately growing hepatomas, the enzyme that is responsible for demethylating proteins, epsilon-alkyllysinase (epsilon-slkyl-L-lysine:oxygen oxidoreductase; EC 1.5.3.4), had an inverse relationship to the rate of tumor growth, thus suggesting a possible physiological antagonism. When isolated rat liver nuclei were methylated in vitro with S-adenosyl-L-[methyl-14 C]methionine as methyl donor, H2SO4-insoluble protein and histones had almost equal amounts of methyl-14 C incorporated. However, amino acid analysis revealed that methylated arginines are the predominant form of radioactivity in the H2SO4-insoluble protein (product of protein methylase I), while methylated lysines are the major methylated amino acids in the histones (product of protein methylase III). Furthermore, the hydrolysate of the H2SO4-insoluble protein showed four unknown radioactivity peaks on the amino acid analyzer in addition to the known methylated arginine and lysine derivatives."} {"id": "PMID:164279", "title": "The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities.", "content": "Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity.", "contents": "The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity."} {"id": "PMID:164280", "title": "The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies.", "content": "Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies.", "contents": "The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies. Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies."} {"id": "PMID:164281", "title": "Specific depression of the antitumor cellular immune response with autologous tumor homogenate.", "content": "A momogenate of an SV40-transformed firbosarcoma of BALB/c mice (E4 tumor) injected i.p. into E4, tumor-immune syngeneic mice specifically depressed their cell-mediated immune responses to autologous tumor cells, as measured by a radioisotopic foot pad assay. The fraction of the tumor homogenate that brought about this depression was present in the high-speed supernatant and pellet of a 3 M KCl extract of the tumor. The specificity of the depression was shown in three ways: (a) the serum of E4 tumor-immune mice, but not of normal mice, given injections of E4 tumor homogenate 24 hr previously, suppressed antitumor immunity in vitro, as measured by the release of 51Cr from labeled E4 tumor cells incubated with spleen cells from tumor-immune animals; (b) the i.p. inoculation of E4 tumor homogenate did not alter the cellular immune response of tuberculin-sensitized mice to tuberculin; and (c) the i.p. injection of a homogenate of antigenically unrelated tumor did not depress the cellular immune response of E4 tumor-immune mice to E4 tumor cells.", "contents": "Specific depression of the antitumor cellular immune response with autologous tumor homogenate. A momogenate of an SV40-transformed firbosarcoma of BALB/c mice (E4 tumor) injected i.p. into E4, tumor-immune syngeneic mice specifically depressed their cell-mediated immune responses to autologous tumor cells, as measured by a radioisotopic foot pad assay. The fraction of the tumor homogenate that brought about this depression was present in the high-speed supernatant and pellet of a 3 M KCl extract of the tumor. The specificity of the depression was shown in three ways: (a) the serum of E4 tumor-immune mice, but not of normal mice, given injections of E4 tumor homogenate 24 hr previously, suppressed antitumor immunity in vitro, as measured by the release of 51Cr from labeled E4 tumor cells incubated with spleen cells from tumor-immune animals; (b) the i.p. inoculation of E4 tumor homogenate did not alter the cellular immune response of tuberculin-sensitized mice to tuberculin; and (c) the i.p. injection of a homogenate of antigenically unrelated tumor did not depress the cellular immune response of E4 tumor-immune mice to E4 tumor cells."} {"id": "PMID:164282", "title": "Chromosome analysis of a simian virus 40-transformed mouse cell line and two variant sublines that are resistant to cytochalasin B1.", "content": "The chromosomes of an SV40-transformed mouse cell line, SVT2, were analyzed by the acetic-saline-Giemsa banding technique. By contrast to most established mouse lines, SVT2 cells possess a remarkably homogeneous chromosome complement and contain two copies of most chromosomes. However, trisomy for chromosome 3 is a distinct feature of this cell line. Chromosomes 1, 3, 14, and 19 have given rise to biarmed markers. Two Cytochalasin B-resistant sublines derived from SVT2 are also essentially diploid for all autosomes but contain only one chromosome X; they display an even greater homogeneity than does the SVT2 parental cell line. Each of the Cytochalasin B-resistant cell lines has lost one or several of the biarmed markers from SVT2 and new ones have appeared. Both cell lines have lost one copy of chromosome 3 and one chromosome X. The results presented illustrate the advantages of cells of defined chromosome constitution, like STV2 cells and derived sublines, to study specific interactions between transforming virus and host chromosomes. The possible role of SV40 in the maintenance of the pseudodiploid karyotype of SVT2 is also discussed.", "contents": "Chromosome analysis of a simian virus 40-transformed mouse cell line and two variant sublines that are resistant to cytochalasin B1. The chromosomes of an SV40-transformed mouse cell line, SVT2, were analyzed by the acetic-saline-Giemsa banding technique. By contrast to most established mouse lines, SVT2 cells possess a remarkably homogeneous chromosome complement and contain two copies of most chromosomes. However, trisomy for chromosome 3 is a distinct feature of this cell line. Chromosomes 1, 3, 14, and 19 have given rise to biarmed markers. Two Cytochalasin B-resistant sublines derived from SVT2 are also essentially diploid for all autosomes but contain only one chromosome X; they display an even greater homogeneity than does the SVT2 parental cell line. Each of the Cytochalasin B-resistant cell lines has lost one or several of the biarmed markers from SVT2 and new ones have appeared. Both cell lines have lost one copy of chromosome 3 and one chromosome X. The results presented illustrate the advantages of cells of defined chromosome constitution, like STV2 cells and derived sublines, to study specific interactions between transforming virus and host chromosomes. The possible role of SV40 in the maintenance of the pseudodiploid karyotype of SVT2 is also discussed."} {"id": "PMID:164283", "title": "Amino- and carboxyl-terminal analyses of hepatoma lactate dehydrogenase isozymes.", "content": "The M4 isozyme of lactate dehydrogenase was purified to homogeneity from normal rat liver and from two Morris hepatomas (7777 and 7793). Amino-terminal analyses with fluorodinitrobenzene failed to detect the presence of free amino-terminal residues in each enzyme studied. Each enzyme contained between 3.7 and 4.1 moles of protein-bound acetyl groups per mole of enzyme. The amino-terminal peptide, characterized as N-acetylalanylalanine, was isolated from Pronase digests of each isozyme preparation, and quantitative recovery experiments indicated that all acetyl residues were bound at the amino termini. Carboxylterminal analyses demonstrated phenylalanine to be the carboxyl-terminal residue in each enzyme studied. These data indicate no differences in either amino- or carboxyl-terminal regions of the hepatoma M4 isozymes compared to normal liver M4 isozyme.", "contents": "Amino- and carboxyl-terminal analyses of hepatoma lactate dehydrogenase isozymes. The M4 isozyme of lactate dehydrogenase was purified to homogeneity from normal rat liver and from two Morris hepatomas (7777 and 7793). Amino-terminal analyses with fluorodinitrobenzene failed to detect the presence of free amino-terminal residues in each enzyme studied. Each enzyme contained between 3.7 and 4.1 moles of protein-bound acetyl groups per mole of enzyme. The amino-terminal peptide, characterized as N-acetylalanylalanine, was isolated from Pronase digests of each isozyme preparation, and quantitative recovery experiments indicated that all acetyl residues were bound at the amino termini. Carboxylterminal analyses demonstrated phenylalanine to be the carboxyl-terminal residue in each enzyme studied. These data indicate no differences in either amino- or carboxyl-terminal regions of the hepatoma M4 isozymes compared to normal liver M4 isozyme."} {"id": "PMID:164285", "title": "Histochemical observations on uptake of L-dopa into endocrine cells of the rat pituitary gland during the postnatal development.", "content": "The uptake of L-dopa into the cells of the adenohypophysis of the rat was studied during the postnatal development and at adult age using the formaldehyde-induced fluorescence method (FIF). The cells taking up L-dopa were classified by Alcian blue-PAS-Orange G staining. The correlation between the cells taking up L-dopa and those containing tryptophyl-peptide was estimated during the postnatal period and in adult rats. The cells containing tryptophyl-peptide were demonstrated using fluorescence induced by treatment with combined formaldehyde and acetyl chloride vapour. The following observations were made: 1) Great majority of the cells taking up L-dopa did not contain tryptophyl-peptide. Thus the accumulation of L-dopa into the cells of pars distalis is not due to accumulation of L-dopa into the cells by the same transport mechanism as the amino acids for tryptophyl-peptide. 2) Of the cells taking up L-dopa in the adult rats 96% were chromophobes, 2.0% acidophilic cells (somatotrophs and cells producing prolactin), 0.9% R-mucoid cells (corticotrophs), and 1.2% S1- and S2-mucoid cells (gonadotrophs and thyrotrophs). At 10 and 25 days' age the relative numbers of the cells taking up L-dopa were about the same. 3) Pretreatment with nialamide caused only a slight increase in the number of the cells taking up L-dopa. The decrease in the number of the cells uptaking L-dopa of the pars distalis, which takes place after 5 weeks' age is thus not caused by the increased MAO-activity. 4) Strongly chromophilic cells did not take up L-dopa. At the light of our results it seems evident that L-dopa is taken up by the chromophobic cells when these differentiate into chromophilic cells. The accumulation of L-dopa may be a sign of an active transport of amino acids into the cells. The accumulation of L-dopa into the chromophobic stellate and follicular cells may reflect their metabolic activity. These cells probably have an important role in the production of the hormones of the pars distalis.", "contents": "Histochemical observations on uptake of L-dopa into endocrine cells of the rat pituitary gland during the postnatal development. The uptake of L-dopa into the cells of the adenohypophysis of the rat was studied during the postnatal development and at adult age using the formaldehyde-induced fluorescence method (FIF). The cells taking up L-dopa were classified by Alcian blue-PAS-Orange G staining. The correlation between the cells taking up L-dopa and those containing tryptophyl-peptide was estimated during the postnatal period and in adult rats. The cells containing tryptophyl-peptide were demonstrated using fluorescence induced by treatment with combined formaldehyde and acetyl chloride vapour. The following observations were made: 1) Great majority of the cells taking up L-dopa did not contain tryptophyl-peptide. Thus the accumulation of L-dopa into the cells of pars distalis is not due to accumulation of L-dopa into the cells by the same transport mechanism as the amino acids for tryptophyl-peptide. 2) Of the cells taking up L-dopa in the adult rats 96% were chromophobes, 2.0% acidophilic cells (somatotrophs and cells producing prolactin), 0.9% R-mucoid cells (corticotrophs), and 1.2% S1- and S2-mucoid cells (gonadotrophs and thyrotrophs). At 10 and 25 days' age the relative numbers of the cells taking up L-dopa were about the same. 3) Pretreatment with nialamide caused only a slight increase in the number of the cells taking up L-dopa. The decrease in the number of the cells uptaking L-dopa of the pars distalis, which takes place after 5 weeks' age is thus not caused by the increased MAO-activity. 4) Strongly chromophilic cells did not take up L-dopa. At the light of our results it seems evident that L-dopa is taken up by the chromophobic cells when these differentiate into chromophilic cells. The accumulation of L-dopa may be a sign of an active transport of amino acids into the cells. The accumulation of L-dopa into the chromophobic stellate and follicular cells may reflect their metabolic activity. These cells probably have an important role in the production of the hormones of the pars distalis."} {"id": "PMID:164286", "title": "Intranuclear and cytoplasmic annulate lamellae in grasshopper spermatocytes (genus Melanoplus).", "content": "Intranuclear and cytoplasmic annulate lamellae were studied in grasshopper spermatocytes (Melanoplus) with the electron microscope. Although cytoplasmic annulate lamellae were observed in all three species examined, intranuclear annulate lamellae were found in only one species. The intranuclear annulate lamellae encompass certain nuclear material adjacent to the nuclear envelope forming a vesicle that is extruded into the spermatocyte cytoplasm. In this same species, cytoplasmic annulate lamellae are seen contiguous with granular masses of varying size. These structures were noted as being morphologically indistinguishable from the \"yolk nuclei\" of dragonfly oocytes (Kessel and Beams, 1969; Kessel, 1973).", "contents": "Intranuclear and cytoplasmic annulate lamellae in grasshopper spermatocytes (genus Melanoplus). Intranuclear and cytoplasmic annulate lamellae were studied in grasshopper spermatocytes (Melanoplus) with the electron microscope. Although cytoplasmic annulate lamellae were observed in all three species examined, intranuclear annulate lamellae were found in only one species. The intranuclear annulate lamellae encompass certain nuclear material adjacent to the nuclear envelope forming a vesicle that is extruded into the spermatocyte cytoplasm. In this same species, cytoplasmic annulate lamellae are seen contiguous with granular masses of varying size. These structures were noted as being morphologically indistinguishable from the \"yolk nuclei\" of dragonfly oocytes (Kessel and Beams, 1969; Kessel, 1973)."} {"id": "PMID:164287", "title": "The fine structure and phosphatase cytochemistry of the golgi complex and associated structures in the sertoli cells of Syrian hamsters.", "content": "The Golgi complex in the Sertoli cell of the Syrian hamster is well developed and consists of stacks of cisternae and associated vesicles. The inner- and outermost cisternae of the Golgi stacks are usually moderately dilated and exhibit numerous fenestrations. The middle portions of the intermediate cisternae are greatly flattened and not fenestrated, but toward the periphery these cisternae gradually become dilated and show a few fenestrations. On the inner aspect of the Golgi stacks the following structures are seen frequently: (1) one or two series of linearly arrayed circular profiles some of which are interconnected by tubules; (2) networks of anastomosing tubules with circular or oval meshes (800 to 1200 A in diameter); and/or (3) irregularly disposed tubules. The circular profiles and tubules are approximately 450 A in diameter. Acid phosphatase activity was localized in these anastomosing tubules when the tissues were incubated for more than one hour in a modified Gomori's medium (Barka and Anderson, 1963). Strong thiamine pyrophosphatase activity was demonstrated in the inner one to three cisternae of the Golgi stacks but not in the associated tubules. The system of the Golgi associated tubules is morphologically and histochemically distinct from the Golgi stacks and is probably equivalent to the Golgi-endoplasmic reticulum-lysosome system (GERL) in other cell types. The three dimensional aspects of the GERL-equivalent system are discussed.", "contents": "The fine structure and phosphatase cytochemistry of the golgi complex and associated structures in the sertoli cells of Syrian hamsters. The Golgi complex in the Sertoli cell of the Syrian hamster is well developed and consists of stacks of cisternae and associated vesicles. The inner- and outermost cisternae of the Golgi stacks are usually moderately dilated and exhibit numerous fenestrations. The middle portions of the intermediate cisternae are greatly flattened and not fenestrated, but toward the periphery these cisternae gradually become dilated and show a few fenestrations. On the inner aspect of the Golgi stacks the following structures are seen frequently: (1) one or two series of linearly arrayed circular profiles some of which are interconnected by tubules; (2) networks of anastomosing tubules with circular or oval meshes (800 to 1200 A in diameter); and/or (3) irregularly disposed tubules. The circular profiles and tubules are approximately 450 A in diameter. Acid phosphatase activity was localized in these anastomosing tubules when the tissues were incubated for more than one hour in a modified Gomori's medium (Barka and Anderson, 1963). Strong thiamine pyrophosphatase activity was demonstrated in the inner one to three cisternae of the Golgi stacks but not in the associated tubules. The system of the Golgi associated tubules is morphologically and histochemically distinct from the Golgi stacks and is probably equivalent to the Golgi-endoplasmic reticulum-lysosome system (GERL) in other cell types. The three dimensional aspects of the GERL-equivalent system are discussed."} {"id": "PMID:164288", "title": "Accumulation of collagen-containing vacuoles in osteoblasts after administration of colchicine.", "content": "Embryonic mouse radii were cultured in the presence of colchicine or vinblastine and subsequently examined in the electron microscope. As a result of the administration of these drugs large numbers of vacuoles accumulated in the cytoplasm of the osteoblasts. The electron-dense contents of at least many of the vacuoles most probably consisted of collagen. This conclusion was based on the results of special staining methods and on the similarity of the vacuoles to collagen vacuoles described in the literature. The observations made in this study provide morphological evidence that colchicine and vinblastine disturb the secretion of collagen.", "contents": "Accumulation of collagen-containing vacuoles in osteoblasts after administration of colchicine. Embryonic mouse radii were cultured in the presence of colchicine or vinblastine and subsequently examined in the electron microscope. As a result of the administration of these drugs large numbers of vacuoles accumulated in the cytoplasm of the osteoblasts. The electron-dense contents of at least many of the vacuoles most probably consisted of collagen. This conclusion was based on the results of special staining methods and on the similarity of the vacuoles to collagen vacuoles described in the literature. The observations made in this study provide morphological evidence that colchicine and vinblastine disturb the secretion of collagen."} {"id": "PMID:164289", "title": "SV40-transformed cells with temperature-dependent serum requirements.", "content": "We have isolated temperature-sensitive SV40-transformed 3T3 cells which are unable to grow in low or depleted serum at the nonpermissive temperature. At 39 degrees C, these cells do not grow in 1 percent serum, but they grow if the serum concentration is raised to 10 percent. At 32 degrees they grow in both serum concentrations. This phenotype seems to be due to a cellular mutation, as the virus rescued from these cells is wild-type. We tested whether other characteristics of transformed cells were expressed in a temperature sensitive way. While high saturation density is ts in these cells, other parameters of transformation are expressed at both temperatures. In addition, when these cells are incubated in low serum at 39 degrees C, they keep synthesizing DNA and lose viability very fast, while under the same conditions normal 3T3 cells remain viable for long times and are unable to initiate DNA synthesis. These cells therefore do not appear to revert to a normal phenotype at the high temperature, and they are more likely to represent transformed cell variants with a temperature-dependent serum requirement.", "contents": "SV40-transformed cells with temperature-dependent serum requirements. We have isolated temperature-sensitive SV40-transformed 3T3 cells which are unable to grow in low or depleted serum at the nonpermissive temperature. At 39 degrees C, these cells do not grow in 1 percent serum, but they grow if the serum concentration is raised to 10 percent. At 32 degrees they grow in both serum concentrations. This phenotype seems to be due to a cellular mutation, as the virus rescued from these cells is wild-type. We tested whether other characteristics of transformed cells were expressed in a temperature sensitive way. While high saturation density is ts in these cells, other parameters of transformation are expressed at both temperatures. In addition, when these cells are incubated in low serum at 39 degrees C, they keep synthesizing DNA and lose viability very fast, while under the same conditions normal 3T3 cells remain viable for long times and are unable to initiate DNA synthesis. These cells therefore do not appear to revert to a normal phenotype at the high temperature, and they are more likely to represent transformed cell variants with a temperature-dependent serum requirement."} {"id": "PMID:164290", "title": "The interaction of estradiol-receptor protein with the genome: an argument for the existence of undetected specific sites.", "content": "In extracts from rat and calf uterus, the steroid hormone 17 beta-estradiol stimulates the binding of its specific receptor protein to DNA. This interaction appears to be of low affinity (half of the estradiol-activated, 5S receptor bound at 300-400 mug/ml DNA) and nonspecific with respect to DNA base sequence. No binding to double-stranded RNA is observed. These findings are consistent with several in vivo observations. In particular, when the cytoplasmic receptor protein binds hormone, it migrates to the cell nucleus to an extent consistent with its affinity for DNA in vitro, and this in vivo nuclear binding is uniform and nonsaturable in the testable range (to greater than 3 times 10-4 sites per cell). The level of biological response appears to parallel the hormone dose up to these high levels of receptor binding. How are these observations to be reconciled with the prevalent view of steroid receptors as gene control proteins regulating transcription at specific loci on the genome? Our model is based on an analogy with the DNA binding properties of the E. coli lac repressor protein. We believe that the estradiol receptor exerts its effect by binding to a small number of high affinity sites on the genome, while also having a finite low affinity for nonspecific DNA sequences. These nonspecific loci, because of their vast number, completely mask the presence of the high affinity sites. We estimate that up to 10-3 specific sites, with affinities in the range 10- minus 8 minus 10- minus 10 M, could exist without being detected by bulk binding assays currently in use. However, alternative approaches should allow detection of these sites, and some of these are suggested.", "contents": "The interaction of estradiol-receptor protein with the genome: an argument for the existence of undetected specific sites. In extracts from rat and calf uterus, the steroid hormone 17 beta-estradiol stimulates the binding of its specific receptor protein to DNA. This interaction appears to be of low affinity (half of the estradiol-activated, 5S receptor bound at 300-400 mug/ml DNA) and nonspecific with respect to DNA base sequence. No binding to double-stranded RNA is observed. These findings are consistent with several in vivo observations. In particular, when the cytoplasmic receptor protein binds hormone, it migrates to the cell nucleus to an extent consistent with its affinity for DNA in vitro, and this in vivo nuclear binding is uniform and nonsaturable in the testable range (to greater than 3 times 10-4 sites per cell). The level of biological response appears to parallel the hormone dose up to these high levels of receptor binding. How are these observations to be reconciled with the prevalent view of steroid receptors as gene control proteins regulating transcription at specific loci on the genome? Our model is based on an analogy with the DNA binding properties of the E. coli lac repressor protein. We believe that the estradiol receptor exerts its effect by binding to a small number of high affinity sites on the genome, while also having a finite low affinity for nonspecific DNA sequences. These nonspecific loci, because of their vast number, completely mask the presence of the high affinity sites. We estimate that up to 10-3 specific sites, with affinities in the range 10- minus 8 minus 10- minus 10 M, could exist without being detected by bulk binding assays currently in use. However, alternative approaches should allow detection of these sites, and some of these are suggested."} {"id": "PMID:164291", "title": "Chicken leukosis virus genome sequences in DNA from normal chick cells and virus-induced bursal lymphomas.", "content": "Genome sequences of two recent field isolates of avian leukosis viruses in the DNA of normal and neoplastic chicken cells were studied by DNA-RNA hybridization under conditions of DNA excess. Comparisons were made between 60-70S RNA from these viruses and that of a chicken endogenous type C virus (RAV-0), and of a series of \"laboratory\" leukosis and sarcoma viruses, by competitive hybridization analysis. A minimum of 18% of the genome sequences of both ALV isolates detected in DNA from lymphomas they induced were not detected in normal chicken DNA. The vast majority of the fraction of RNA sequences from ALV which do form hybrids with normal chick DNA appear to be reacting with the endogenous provirus of RAV-0. The genomic representation of a variety of avian leukosis and sarcoma viruses in normal chicken cells could not be distinguished by these methods (except that 13% of the RAV-0 genome was not shared with any of the other viruses). In contrast, the portion of the ALV genome exogenous to the normal chicken geome showed significant divergence from that of two sarcoma viruses (Pr RSV-C and B-77). The increased hybridization of ALV RNA with lymphoma DNA was used to detect the appearance of ALV specific sequences in the bursa of Fabricius following infection.increased hybridization was correlated with both the time after infection and the extent of replacement of the bursa by lymphoma. About one half of the increase in hybridization preceded histologic evidence of transformation.", "contents": "Chicken leukosis virus genome sequences in DNA from normal chick cells and virus-induced bursal lymphomas. Genome sequences of two recent field isolates of avian leukosis viruses in the DNA of normal and neoplastic chicken cells were studied by DNA-RNA hybridization under conditions of DNA excess. Comparisons were made between 60-70S RNA from these viruses and that of a chicken endogenous type C virus (RAV-0), and of a series of \"laboratory\" leukosis and sarcoma viruses, by competitive hybridization analysis. A minimum of 18% of the genome sequences of both ALV isolates detected in DNA from lymphomas they induced were not detected in normal chicken DNA. The vast majority of the fraction of RNA sequences from ALV which do form hybrids with normal chick DNA appear to be reacting with the endogenous provirus of RAV-0. The genomic representation of a variety of avian leukosis and sarcoma viruses in normal chicken cells could not be distinguished by these methods (except that 13% of the RAV-0 genome was not shared with any of the other viruses). In contrast, the portion of the ALV genome exogenous to the normal chicken geome showed significant divergence from that of two sarcoma viruses (Pr RSV-C and B-77). The increased hybridization of ALV RNA with lymphoma DNA was used to detect the appearance of ALV specific sequences in the bursa of Fabricius following infection.increased hybridization was correlated with both the time after infection and the extent of replacement of the bursa by lymphoma. About one half of the increase in hybridization preceded histologic evidence of transformation."} {"id": "PMID:164292", "title": "Distribution of murine type B and type C viral nucleic acid sequences in template active and template inactive chromatin.", "content": "Template active chromatin and template inactive chromatin have been fractionated from mouse cells infected with the Moloney strain of murine leukemia virus. In vivo the cells produce abundant Rna homologous to Moloney leukemia virus, but do not produce either globin mRNA or RNA homologous to type B mouse mammary tumor virus. The DNA extracted from the template active chromatin or template inactive chromatin contained equal amounts of sequences homologous to Moloney type C virus, to type B virus, or to globin mRNA. The results are discussed with regard to the in vivo structure of chromatin and the difficulties in fractionating chromatin in vitro.", "contents": "Distribution of murine type B and type C viral nucleic acid sequences in template active and template inactive chromatin. Template active chromatin and template inactive chromatin have been fractionated from mouse cells infected with the Moloney strain of murine leukemia virus. In vivo the cells produce abundant Rna homologous to Moloney leukemia virus, but do not produce either globin mRNA or RNA homologous to type B mouse mammary tumor virus. The DNA extracted from the template active chromatin or template inactive chromatin contained equal amounts of sequences homologous to Moloney type C virus, to type B virus, or to globin mRNA. The results are discussed with regard to the in vivo structure of chromatin and the difficulties in fractionating chromatin in vitro."} {"id": "PMID:164293", "title": "Methylated nucleotides block 5' terminus of HeLa cell messenger RNA.", "content": "Polyadenylylated [poly(A)+] mRNA from HeLa cells that were labeled with [3H-methyl]-methionine and 14C-uridine was isolated by poly(U)-Sepharose chromatography. The presence of approximately two methyl groups per 1000 nucleotides of poly(A)+ RNA was calculated from the 3H/14C ratios and known degrees of methylation of 18S and 28S ribosomal RNAs. All four 2'-O-methylribonucleosides, but only two base-methylated derivatives, 7-methylguanosine (7MeG) and 6-methyladenosine (6MeA), were identified. 6MeA was the major component accounting for approximately 50% of the total methyl-labeled ribonucleosides. 7MeG, comprising about 10% of the total, was present exclusively at the 5' terminus of the poly(A)+ RNA and could be removed by periodate oxidation and beta elimination. Evidence for a 5' to 5' linkage of 7MeG to adjacent 2'-O-methylribonucleosides through at least two and probably three phosphates to give structures of the type 7MeG5'ppp5pNMep- and 7MeG5'ppp5'NMepNmep- was presented. The previous finding of similar sequences of methylated nucleotides in mRNA synthesized in vitro by enzymes associated with virus cores indicates that blocked 5' termini may be a characteristic feature of mRNAs that function in eucaryotic cells.", "contents": "Methylated nucleotides block 5' terminus of HeLa cell messenger RNA. Polyadenylylated [poly(A)+] mRNA from HeLa cells that were labeled with [3H-methyl]-methionine and 14C-uridine was isolated by poly(U)-Sepharose chromatography. The presence of approximately two methyl groups per 1000 nucleotides of poly(A)+ RNA was calculated from the 3H/14C ratios and known degrees of methylation of 18S and 28S ribosomal RNAs. All four 2'-O-methylribonucleosides, but only two base-methylated derivatives, 7-methylguanosine (7MeG) and 6-methyladenosine (6MeA), were identified. 6MeA was the major component accounting for approximately 50% of the total methyl-labeled ribonucleosides. 7MeG, comprising about 10% of the total, was present exclusively at the 5' terminus of the poly(A)+ RNA and could be removed by periodate oxidation and beta elimination. Evidence for a 5' to 5' linkage of 7MeG to adjacent 2'-O-methylribonucleosides through at least two and probably three phosphates to give structures of the type 7MeG5'ppp5pNMep- and 7MeG5'ppp5'NMepNmep- was presented. The previous finding of similar sequences of methylated nucleotides in mRNA synthesized in vitro by enzymes associated with virus cores indicates that blocked 5' termini may be a characteristic feature of mRNAs that function in eucaryotic cells."} {"id": "PMID:164297", "title": "Organ-specific effects of DNA methylation by alkylating agents in the inbred Swiss mouse.", "content": "Young adult inbred Swiss mice given single or repeated equitoxic doses of N-methyl-N-nitrosourea (MNUA) or methyl methanesulphonate (MMS) develop thymomas and pulmonary adenomas only following MNUA in spite of nearly identical overall alkylation of DNA of tumour target tissues by both agents due mainly to the biologically ineffective product 7-methylguanine. The main difference in DNA alkylation was the production of O6-methylguinine, a known pre-mutagenic product, by MNUA in amounts 10 or more times as large as following MMS. This supports the possibility that somatic mutations are a part of the process of carcinogenesis.", "contents": "Organ-specific effects of DNA methylation by alkylating agents in the inbred Swiss mouse. Young adult inbred Swiss mice given single or repeated equitoxic doses of N-methyl-N-nitrosourea (MNUA) or methyl methanesulphonate (MMS) develop thymomas and pulmonary adenomas only following MNUA in spite of nearly identical overall alkylation of DNA of tumour target tissues by both agents due mainly to the biologically ineffective product 7-methylguanine. The main difference in DNA alkylation was the production of O6-methylguinine, a known pre-mutagenic product, by MNUA in amounts 10 or more times as large as following MMS. This supports the possibility that somatic mutations are a part of the process of carcinogenesis."} {"id": "PMID:164301", "title": "Fluorometry of citrate in serum, with use of citrate (pro-3S)-lyase.", "content": "We describe a procedure for enzymatic assay of citrate in human serum. The citrate is degraded to acetate and oxaloacetate with citrate oxaloacetate-lyase (pro-3S-CH2-COO- yields acetate) (EC 4.1.3.6). Some oxaloacetate loses CO2 to form pyruvate. Addition of malate and lactate dehydrogenases (EC 1.1.1.37 and 1.1.1.27) permits determination of the oxaloacetate and pyruvate generated, and thus of the citrate concentration. The decrease in NADH concentration is measured fluorometrically. Results obtained for 30 consecutive human sera by this procedure were compared to the procedure in which the citrate is converted to pentabromoacetone. There was no statistically significant difference in values obtained by the two procedures. The range of values (mean plus or minus 2 SD) found for sera from 25 blood donors by this procedure was 12.8-27.2 mg/liter (mean, 19.0 mg/liter). Serum citrate as measured by both procedures during a glucose tolerance test was decreased from initial values under the influence of administered glucose (and endogenous insulin). Insulin concentrations were also measured during these glucose-tolerance tests. Citrate concentrations remain subnormal after the glucose and insulin concentrations return to their initial values. This accords with published reports.", "contents": "Fluorometry of citrate in serum, with use of citrate (pro-3S)-lyase. We describe a procedure for enzymatic assay of citrate in human serum. The citrate is degraded to acetate and oxaloacetate with citrate oxaloacetate-lyase (pro-3S-CH2-COO- yields acetate) (EC 4.1.3.6). Some oxaloacetate loses CO2 to form pyruvate. Addition of malate and lactate dehydrogenases (EC 1.1.1.37 and 1.1.1.27) permits determination of the oxaloacetate and pyruvate generated, and thus of the citrate concentration. The decrease in NADH concentration is measured fluorometrically. Results obtained for 30 consecutive human sera by this procedure were compared to the procedure in which the citrate is converted to pentabromoacetone. There was no statistically significant difference in values obtained by the two procedures. The range of values (mean plus or minus 2 SD) found for sera from 25 blood donors by this procedure was 12.8-27.2 mg/liter (mean, 19.0 mg/liter). Serum citrate as measured by both procedures during a glucose tolerance test was decreased from initial values under the influence of administered glucose (and endogenous insulin). Insulin concentrations were also measured during these glucose-tolerance tests. Citrate concentrations remain subnormal after the glucose and insulin concentrations return to their initial values. This accords with published reports."} {"id": "PMID:164302", "title": "Hyperlipoproteinaemia in ponies: mechanisms and response to therapy.", "content": "(I) The lipid and lipoprotein concentrations in sera of 4 healthy and 9 hyperlipaemic patients were determined. From the results of the analyses, it is suggested that three types of hyperlipoproteinaemia can be distinguished in ponies: (a) Type 1, characterised by a very pronounced increase in only the very low density lipoproteins (VLDL); (b) Type 2, in which there is a pronounced increase in the chylomicrons (Chylo) and the very low density lipoproteins (VLDL); (c) Type 3, which can be the result of fasting and is characterised by a moderate increase in the concentration of chylomicrons and a greater increase in very low density lipoproteins. It is suggested that hyperlipoproteinaemia in ponies can be classified on the basis of electrophoretic patterns. (II) To gather more information on the metabolism of extra offered lipids, blood from ponies suffering from two different types of hyperlipoproteinaemia was transfused into normal ponies and the changes in lipid and lipoprotein concentrations in the blood serum were followed. The reactions were different. When heparin was used as anticoagulant a great increase in chylomicrons and a significant increase in very low density lipoproteins in a healthy pony was observed. When sodium citrate was used as anticoagulant a clear increase in the VLDL fraction only was noticed.", "contents": "Hyperlipoproteinaemia in ponies: mechanisms and response to therapy. (I) The lipid and lipoprotein concentrations in sera of 4 healthy and 9 hyperlipaemic patients were determined. From the results of the analyses, it is suggested that three types of hyperlipoproteinaemia can be distinguished in ponies: (a) Type 1, characterised by a very pronounced increase in only the very low density lipoproteins (VLDL); (b) Type 2, in which there is a pronounced increase in the chylomicrons (Chylo) and the very low density lipoproteins (VLDL); (c) Type 3, which can be the result of fasting and is characterised by a moderate increase in the concentration of chylomicrons and a greater increase in very low density lipoproteins. It is suggested that hyperlipoproteinaemia in ponies can be classified on the basis of electrophoretic patterns. (II) To gather more information on the metabolism of extra offered lipids, blood from ponies suffering from two different types of hyperlipoproteinaemia was transfused into normal ponies and the changes in lipid and lipoprotein concentrations in the blood serum were followed. The reactions were different. When heparin was used as anticoagulant a great increase in chylomicrons and a significant increase in very low density lipoproteins in a healthy pony was observed. When sodium citrate was used as anticoagulant a clear increase in the VLDL fraction only was noticed."} {"id": "PMID:164303", "title": "The formation of 2-hydroxybutyric acid in experimental animals.", "content": "1. The formation of 2-hydroxybutyric acid (2-HB) has been studied by animal experiments. 2. 2-HB was excreted in the urine together with lactic acid following intravenous administration of huge amounts of 3-hydroxybutyric acid (sodium salt) to a dog. 3. Rats made diabetic by an injection of streptozotocin were found to excrete large quantities of 2HB in the urine (up to 300 mumol/24 h) together with the development of ketoacidosis. 4. The use of 14-C-labelled precursors clearly showed that the amino acids methionine, threonine and homoserine can be converted to 2-HB. 5. 2-Aminobutyric acid is also converted to 2-HB, with 2-oxobutyric acid as an intermediate metabolite. The ratio between the urinary concentrations of 2-HB and 2-oxobutyric acid was increased by the ingestion of ethanol. 6. In normal rats neither a prolonged fasting period nor loading with large doses of methionine, threonine and homoserine resulted in the excretion of 2-HB. 7. The mechanisms behind the formation of 2-HB are discussed, and it is concluded that an increased NADH2/NAD ratio in the cytoplasma is the most important factor.", "contents": "The formation of 2-hydroxybutyric acid in experimental animals. 1. The formation of 2-hydroxybutyric acid (2-HB) has been studied by animal experiments. 2. 2-HB was excreted in the urine together with lactic acid following intravenous administration of huge amounts of 3-hydroxybutyric acid (sodium salt) to a dog. 3. Rats made diabetic by an injection of streptozotocin were found to excrete large quantities of 2HB in the urine (up to 300 mumol/24 h) together with the development of ketoacidosis. 4. The use of 14-C-labelled precursors clearly showed that the amino acids methionine, threonine and homoserine can be converted to 2-HB. 5. 2-Aminobutyric acid is also converted to 2-HB, with 2-oxobutyric acid as an intermediate metabolite. The ratio between the urinary concentrations of 2-HB and 2-oxobutyric acid was increased by the ingestion of ethanol. 6. In normal rats neither a prolonged fasting period nor loading with large doses of methionine, threonine and homoserine resulted in the excretion of 2-HB. 7. The mechanisms behind the formation of 2-HB are discussed, and it is concluded that an increased NADH2/NAD ratio in the cytoplasma is the most important factor."} {"id": "PMID:164304", "title": "The quantitation of cyclophosphamide in human blood and urine by mass spectrometry-stable isotope dilution.", "content": "The levels of cyclophosphamide in the blood and the urine of patients have been monitored by direct insertion, electron impact mass spectrometry using the principle of stable isotope dilution. When a tetradeuterated analogue of the drug was added to a sample of blood or urine the concentration of cyclophosphamide could be determined from the ratio of the intensities of the signals (M-CH2 C1) characteristic for cyclophosphamide and the tetradeuterated analogue present in the mass spectrum of a chloroform extract. The procedure is highly specific for cyclophosphamide and obviates the need to use radioactively labelled cyclophosphamide for quantitation of the drug in man.", "contents": "The quantitation of cyclophosphamide in human blood and urine by mass spectrometry-stable isotope dilution. The levels of cyclophosphamide in the blood and the urine of patients have been monitored by direct insertion, electron impact mass spectrometry using the principle of stable isotope dilution. When a tetradeuterated analogue of the drug was added to a sample of blood or urine the concentration of cyclophosphamide could be determined from the ratio of the intensities of the signals (M-CH2 C1) characteristic for cyclophosphamide and the tetradeuterated analogue present in the mass spectrum of a chloroform extract. The procedure is highly specific for cyclophosphamide and obviates the need to use radioactively labelled cyclophosphamide for quantitation of the drug in man."} {"id": "PMID:164305", "title": "A longitudinal assessment of lipid ratios in the diagnosis of type III hyperlipoproteinaemia.", "content": "Type III hyperlipoproteinaemia (HLP) has been overdiagnosed in the past, but still may go undiagnosed because of technical difficulties. This longitudinal study of 19 ultracentrifugally proven cases of Type III HLP shows that 2 lipid ratios can be used to supplement the findings of a floating beta band. These patients have been followed for 3 months to 2.5 years whilst on dietary and/or drug treatment. A group composed of more than 100 Type IIB, Type IV and Type IIB-IV hyperlipoproteinaemic patients has been used for comparison purposes. From a total of 310 ultracentrifugal analyses, it was found that the following 2 ratios have more than a 90 percent predictability for Type III HLP: supernatant cholesterol/supernatant triglyceride greater than or equal to 0.35 (Ratio 2); supernatant cholesterol/whole plasma triglyceride greater than or equal to 0.25 (Ratio 3). These ratios are particularly valuable in Type III HLP when the plasma is grossly hyperlipaemic or when the lipid levels are low because of successful treatment.", "contents": "A longitudinal assessment of lipid ratios in the diagnosis of type III hyperlipoproteinaemia. Type III hyperlipoproteinaemia (HLP) has been overdiagnosed in the past, but still may go undiagnosed because of technical difficulties. This longitudinal study of 19 ultracentrifugally proven cases of Type III HLP shows that 2 lipid ratios can be used to supplement the findings of a floating beta band. These patients have been followed for 3 months to 2.5 years whilst on dietary and/or drug treatment. A group composed of more than 100 Type IIB, Type IV and Type IIB-IV hyperlipoproteinaemic patients has been used for comparison purposes. From a total of 310 ultracentrifugal analyses, it was found that the following 2 ratios have more than a 90 percent predictability for Type III HLP: supernatant cholesterol/supernatant triglyceride greater than or equal to 0.35 (Ratio 2); supernatant cholesterol/whole plasma triglyceride greater than or equal to 0.25 (Ratio 3). These ratios are particularly valuable in Type III HLP when the plasma is grossly hyperlipaemic or when the lipid levels are low because of successful treatment."} {"id": "PMID:164306", "title": "Serum pseudocholinesterase and ceruloplasmin in various types of hyperlipoproteinemia.", "content": "Starting from previous observations emphasizing an increased pseudocholinesterase (PCE) activity in obese and hyperlipemic subjects, the behaviour of this enzyme and of ceruloplasmin was studied in connection with changes of serum lipids and lipoproteins in various types of hyperlipoproteinemia. When compared to values detected in 67 middle-aged normal weight normolipemic subjects, PCE activity was found to be significantly greater (smaller than 0.001) in the 49 overweight subjects without obvious hyperlipemia but presenting a moderate increase of the prebeta electrophoretic fraction. PCE activity was much higher in lean or overweight subjects with endogenous hypertriglyceridemia (68 patients with type IV and 86 patients with mixed hyperlipemia). The slight increase of mean values of PCE activity in the 53 subjects with type II-a was due mainly to overweight subjects, while this enzyme's activity was not significantly changed in lean subjects with pure hypercholesterolemia. PCE activity was positively correlated with serum triglyceride (r equals 0.540; p smaller than 0.001) and the prebeta electrophoretic fraction (r equals 610; p smaller than 0.001). The correlation with beta-lipoproteins was not significant. Ceruloplasmin levels were not significantly changed. It is suggested that elevation of PCE activity could be connected to mechanisms leading to an increased secretion rate of lipoproteins.", "contents": "Serum pseudocholinesterase and ceruloplasmin in various types of hyperlipoproteinemia. Starting from previous observations emphasizing an increased pseudocholinesterase (PCE) activity in obese and hyperlipemic subjects, the behaviour of this enzyme and of ceruloplasmin was studied in connection with changes of serum lipids and lipoproteins in various types of hyperlipoproteinemia. When compared to values detected in 67 middle-aged normal weight normolipemic subjects, PCE activity was found to be significantly greater (smaller than 0.001) in the 49 overweight subjects without obvious hyperlipemia but presenting a moderate increase of the prebeta electrophoretic fraction. PCE activity was much higher in lean or overweight subjects with endogenous hypertriglyceridemia (68 patients with type IV and 86 patients with mixed hyperlipemia). The slight increase of mean values of PCE activity in the 53 subjects with type II-a was due mainly to overweight subjects, while this enzyme's activity was not significantly changed in lean subjects with pure hypercholesterolemia. PCE activity was positively correlated with serum triglyceride (r equals 0.540; p smaller than 0.001) and the prebeta electrophoretic fraction (r equals 610; p smaller than 0.001). The correlation with beta-lipoproteins was not significant. Ceruloplasmin levels were not significantly changed. It is suggested that elevation of PCE activity could be connected to mechanisms leading to an increased secretion rate of lipoproteins."} {"id": "PMID:164307", "title": "Studies on changes in lipid profiles of the rat gastric mucosa with stress ulcers.", "content": "Gastric mucosal lipid patterns were studied in normal and in restrained rats which developed mucosal erosions. Organic solvent extraction, silicic acid column, and thin-layer chromatography were employed to separate and gas-liquid chromatography and spectrophotometry to quantitize the individual lipid components. Chemical analysis revealed profound alterations in the mucosal lipid profiles of rats with gastric mucosal erosions. Cholesterol esters were markedly elevated, cholesterol, free fatty acids and phosphatidylethanolamine were markedly lower in the extracts of ulcerated tissue, and the titer of lysophospholipids was about eight times higher than in the controls. Lipid phosphorus was elevated in stressed rats. The amount of neutral glycolipids was similar for both groups, but tetra- and oligohexoside ceramides, which were present in the gastric mucosa of the control rats, were virtually absent from the ulcerated mucosa. In contrast to the alterations in lipid profile mentioned above, the total lipid weight per tissue preparation was very similar for the ulcerated and normal control groups.", "contents": "Studies on changes in lipid profiles of the rat gastric mucosa with stress ulcers. Gastric mucosal lipid patterns were studied in normal and in restrained rats which developed mucosal erosions. Organic solvent extraction, silicic acid column, and thin-layer chromatography were employed to separate and gas-liquid chromatography and spectrophotometry to quantitize the individual lipid components. Chemical analysis revealed profound alterations in the mucosal lipid profiles of rats with gastric mucosal erosions. Cholesterol esters were markedly elevated, cholesterol, free fatty acids and phosphatidylethanolamine were markedly lower in the extracts of ulcerated tissue, and the titer of lysophospholipids was about eight times higher than in the controls. Lipid phosphorus was elevated in stressed rats. The amount of neutral glycolipids was similar for both groups, but tetra- and oligohexoside ceramides, which were present in the gastric mucosa of the control rats, were virtually absent from the ulcerated mucosa. In contrast to the alterations in lipid profile mentioned above, the total lipid weight per tissue preparation was very similar for the ulcerated and normal control groups."} {"id": "PMID:164308", "title": "Immunoreactive ACTH and cortisol plasma levels during pregnancy. Detection and partial purification of corticotrophin-like placental hormone: the human chorionic corticotrophin (HCC).", "content": "The high plasma cortisol and ACTH levels present in pregnant women as well as the non-parrallelism of their plasma extract dilution curves in comparison with the standard curve in the ACTH radioimmunoassay, are evidence for the presence of an ACTH-like substance during pregnancy which would interfere with the assay. Placental extracts were obtained by acid-acetone extraction, followed by partial purification with oxycellulose and by extraction with porous glass powder. A substance was detected which partially cross-reacted with synthetic human ACTH in the radioimmunoassay and which showed biological activity using the assay procedure described by Liscomb & Nelson. The data sustain the existence of an ACTH-like placental hormone: human chorionic corticotrophin (HCC).", "contents": "Immunoreactive ACTH and cortisol plasma levels during pregnancy. Detection and partial purification of corticotrophin-like placental hormone: the human chorionic corticotrophin (HCC). The high plasma cortisol and ACTH levels present in pregnant women as well as the non-parrallelism of their plasma extract dilution curves in comparison with the standard curve in the ACTH radioimmunoassay, are evidence for the presence of an ACTH-like substance during pregnancy which would interfere with the assay. Placental extracts were obtained by acid-acetone extraction, followed by partial purification with oxycellulose and by extraction with porous glass powder. A substance was detected which partially cross-reacted with synthetic human ACTH in the radioimmunoassay and which showed biological activity using the assay procedure described by Liscomb & Nelson. The data sustain the existence of an ACTH-like placental hormone: human chorionic corticotrophin (HCC)."} {"id": "PMID:164311", "title": "Stature and longitudinal growth in thalassemia major. A study of 229 Greek patients.", "content": "A high percentage of Greek children with homozygous b-thalassemia were short and had a lag in growth, though some severely affected attained normal height. Bone age lagged significantly behind the chronologic age, even in those with normal height for their age. A longitudinal study demonstrated an initial normal growth velocity which decreased after the age of six for males and eight for females. No patient had a spurt of growth at adolescence. Height gain continued up to the age of 21 and then ceased. Statistical analysis with a multiple regression equation showed a significant relationship between the age and height of the patients. Low hemoglobin levels and severity of the disease seemed to hinder normal growth, but neither relationship was statistically significant.", "contents": "Stature and longitudinal growth in thalassemia major. A study of 229 Greek patients. A high percentage of Greek children with homozygous b-thalassemia were short and had a lag in growth, though some severely affected attained normal height. Bone age lagged significantly behind the chronologic age, even in those with normal height for their age. A longitudinal study demonstrated an initial normal growth velocity which decreased after the age of six for males and eight for females. No patient had a spurt of growth at adolescence. Height gain continued up to the age of 21 and then ceased. Statistical analysis with a multiple regression equation showed a significant relationship between the age and height of the patients. Low hemoglobin levels and severity of the disease seemed to hinder normal growth, but neither relationship was statistically significant."} {"id": "PMID:164312", "title": "Effects of clofibrate and a fat-modified diet on serum lipids.", "content": "The combined effect of clofibrate and a fat-modified diet was determined in 17 hyperlipidemic patients: 7 type IIA, 7 type IV, 2 type VI(IIB), and 1 type III. Control serum lipid levels and lipoprotein patterns and their alteration with a fat-modified diet had been determined previously 1/2 to 2 years for 3 patients, and 6 to 10 years for 14 patients. Two grams of clofibrate a day (0.5 gm four times daily) was taken along with the fat-modified diet for 2 to 6 months by 5 patients and for 2 years by 13 patients. The effect of clofibrate and a fat-controlled diet was also determined in 10 normolipidemic men who were subjects of an 18-day test in which the polyunsaturated fat diet was quantitatively prepared and eaten along with 2 gm clofibrate a day (0.5 gm four times daily). The effect of clofibrate on serum cholesterol levels was a further mean reduction in type IIA patients by 19 %, in type III by 23%, in type IV by 12%, in type VI by 7%, and in normolipidemic subjects by 8%. The extent of the additional serum cholesterol reduction with clofibrate in individual hyperlipidemic patients varied from +10% to minus 44% and was not related directly to the type of hyperlipidemia. The extent of reduction appeared related directly to the level of minus S 40-70 (similar to Sf 12-20) lipoprotein fraction in the control serum sample. Serum triglyceride levels were unaffected in type IIA and normolipidemic subjects. Serum triglyceride levels did not change consistently in the 2 type VI patients, rising by 11% in 1 and dropping by 31% in the other. Serum triglyceride levels were significantly (p = 0.001) and consistently reduced by 39% only in type IV patients.", "contents": "Effects of clofibrate and a fat-modified diet on serum lipids. The combined effect of clofibrate and a fat-modified diet was determined in 17 hyperlipidemic patients: 7 type IIA, 7 type IV, 2 type VI(IIB), and 1 type III. Control serum lipid levels and lipoprotein patterns and their alteration with a fat-modified diet had been determined previously 1/2 to 2 years for 3 patients, and 6 to 10 years for 14 patients. Two grams of clofibrate a day (0.5 gm four times daily) was taken along with the fat-modified diet for 2 to 6 months by 5 patients and for 2 years by 13 patients. The effect of clofibrate and a fat-controlled diet was also determined in 10 normolipidemic men who were subjects of an 18-day test in which the polyunsaturated fat diet was quantitatively prepared and eaten along with 2 gm clofibrate a day (0.5 gm four times daily). The effect of clofibrate on serum cholesterol levels was a further mean reduction in type IIA patients by 19 %, in type III by 23%, in type IV by 12%, in type VI by 7%, and in normolipidemic subjects by 8%. The extent of the additional serum cholesterol reduction with clofibrate in individual hyperlipidemic patients varied from +10% to minus 44% and was not related directly to the type of hyperlipidemia. The extent of reduction appeared related directly to the level of minus S 40-70 (similar to Sf 12-20) lipoprotein fraction in the control serum sample. Serum triglyceride levels were unaffected in type IIA and normolipidemic subjects. Serum triglyceride levels did not change consistently in the 2 type VI patients, rising by 11% in 1 and dropping by 31% in the other. Serum triglyceride levels were significantly (p = 0.001) and consistently reduced by 39% only in type IV patients."} {"id": "PMID:164313", "title": "Long-term therapy of viramin D-resistant richets with 25-hydroxycholecalciferol.", "content": "The long-term effects of the vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), were evaluated in 2 children with hypophosphatemic vitamin D-resistant rickets. Serial total balance studies demonstrated an apparent lack of correlation between the effects of the vitamin on intestinal absorption of calcium and phosphorus and both the onset of healing in 1 of the 2 patients treated with 5,000 to 7,500 u of the metabolite and the absence of demonstrable radiologic improvement in another patient in whom the final dosage was 20,000 u. per day. At first, the metabolite induced a positive calcium balance in both patients resulting largely from a reduction in intestinal calcium excretion. Despite a continued positive calcium balance, 1 of the 2 patients did not demonstrate further healing, while in the other patient healing was noted even when total calcium balance was negative. Serum phosphate levels did not return to normal in either patient, nor was phosphate excretion altered by 25-HCC. Serum alkaline phosphatase remained elevated in both. Serum immunoassayable parathyroid hormone levels were consistently normal to high-normal in the 2 patients throughout more than 24 months of observation. No instances of hypercalcemia and only occasional hypercalciuric episodes were noted.", "contents": "Long-term therapy of viramin D-resistant richets with 25-hydroxycholecalciferol. The long-term effects of the vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), were evaluated in 2 children with hypophosphatemic vitamin D-resistant rickets. Serial total balance studies demonstrated an apparent lack of correlation between the effects of the vitamin on intestinal absorption of calcium and phosphorus and both the onset of healing in 1 of the 2 patients treated with 5,000 to 7,500 u of the metabolite and the absence of demonstrable radiologic improvement in another patient in whom the final dosage was 20,000 u. per day. At first, the metabolite induced a positive calcium balance in both patients resulting largely from a reduction in intestinal calcium excretion. Despite a continued positive calcium balance, 1 of the 2 patients did not demonstrate further healing, while in the other patient healing was noted even when total calcium balance was negative. Serum phosphate levels did not return to normal in either patient, nor was phosphate excretion altered by 25-HCC. Serum alkaline phosphatase remained elevated in both. Serum immunoassayable parathyroid hormone levels were consistently normal to high-normal in the 2 patients throughout more than 24 months of observation. No instances of hypercalcemia and only occasional hypercalciuric episodes were noted."} {"id": "PMID:164314", "title": "Effects of high dosage delta-9-tetrahydrocannabinol on sleep patterns in man.", "content": "Electroencephalographic readings and eye movement were recorded in experienced marijuana users under placebo and tetrahydrocannabinol (THC). Four subjects were studied for 3 baseline nights, 3 nights under initial dosage of 70 mg/day, the last 3 nights of a 2-wk period of 210 mg/day, and the first 3 nights of withdrawal. Three other subjects were studied only during the latter 2 conditions. Administration of THC significantly reduced eye movement activity during sleep with rapid eye movements (REM) and, to a lesser extent, the duration of REM itself. Withdrawal led to increases above baseline in both measures but the \"rebound\" effect was greater for eye movement. Stage 4 sleep tended to increase on drug, but this effect was not statistically significant. On withdrawal, stage 4 sleep decreased significantly; this change was marked only on the first withdrawal night. The functional or biological significance of these changes is unclear. Nevertheless, these are the most marked effects of THC on brain electrical activity demonstrated thus far. Since its pattern of effects on sleep appears unique to THC, this drug may prove to be a valuable tool in the elucidation of the pharmacology of sleep. Possible relations between effects on sleep pattern and on behavior are discussed.", "contents": "Effects of high dosage delta-9-tetrahydrocannabinol on sleep patterns in man. Electroencephalographic readings and eye movement were recorded in experienced marijuana users under placebo and tetrahydrocannabinol (THC). Four subjects were studied for 3 baseline nights, 3 nights under initial dosage of 70 mg/day, the last 3 nights of a 2-wk period of 210 mg/day, and the first 3 nights of withdrawal. Three other subjects were studied only during the latter 2 conditions. Administration of THC significantly reduced eye movement activity during sleep with rapid eye movements (REM) and, to a lesser extent, the duration of REM itself. Withdrawal led to increases above baseline in both measures but the \"rebound\" effect was greater for eye movement. Stage 4 sleep tended to increase on drug, but this effect was not statistically significant. On withdrawal, stage 4 sleep decreased significantly; this change was marked only on the first withdrawal night. The functional or biological significance of these changes is unclear. Nevertheless, these are the most marked effects of THC on brain electrical activity demonstrated thus far. Since its pattern of effects on sleep appears unique to THC, this drug may prove to be a valuable tool in the elucidation of the pharmacology of sleep. Possible relations between effects on sleep pattern and on behavior are discussed."} {"id": "PMID:164315", "title": "Bone metastases in Wilms' tumour.", "content": "In a series of 81 patients with a diagnosis of Wilms' tumour seen at the Hospital for Sick Children, Great Ormond Street, between 1960-1972, two patients developed histologically proven bone metastases. In one patient a lump on the head was the presenting symptom of his Wilms' tumour. In the second patient an isolated metastasis developed in the iliac bone 2 3/4 years after complete removal of an encapsulated Wilms' tumour. The bone lesion was outside the previously irradiated volume. Response to treatment was poor and both patients died with further widespread disease. A review of other series confirms the low incidence of bone metastases from Wilms' tumour and the poor prognosis of this complication. This contrasts with a high incidence of pulmonary metastases in which the response to treatment and subsequent survival is good. The value of skeletal surveys and scans in detecting this relatively rare site of metastases from Wilms' tumour is discussed.", "contents": "Bone metastases in Wilms' tumour. In a series of 81 patients with a diagnosis of Wilms' tumour seen at the Hospital for Sick Children, Great Ormond Street, between 1960-1972, two patients developed histologically proven bone metastases. In one patient a lump on the head was the presenting symptom of his Wilms' tumour. In the second patient an isolated metastasis developed in the iliac bone 2 3/4 years after complete removal of an encapsulated Wilms' tumour. The bone lesion was outside the previously irradiated volume. Response to treatment was poor and both patients died with further widespread disease. A review of other series confirms the low incidence of bone metastases from Wilms' tumour and the poor prognosis of this complication. This contrasts with a high incidence of pulmonary metastases in which the response to treatment and subsequent survival is good. The value of skeletal surveys and scans in detecting this relatively rare site of metastases from Wilms' tumour is discussed."} {"id": "PMID:164316", "title": "Some urographic aspects of the horseshoe kidney anomaly-a review of 59 cases.", "content": "The urographic findings in 59 cases of horseshoe kidney are reviewed. Significant degrees of rotation are commoner and more pronounced in the left kidney in these cases than in the right kidney. This factor, rather than obliquity of the kidneys, is more likely to play a part in the development of upper urinary tract obstruction. Reversal of the normal direction of obliquity is not as common as is generally thought. The horseshoe kidney is, more often than not, mildly ectopic. Gross failure of ascent of the kidneys in the abdomen is uncommon. Evidence of pelvi-ureteric obstruction, especially hydronephrosis, occurred in just under half the cases. The reasons for this are discussed. The occurrence of other associated urinary tract anomalies, as well as acquired renal conditions, is considered.", "contents": "Some urographic aspects of the horseshoe kidney anomaly-a review of 59 cases. The urographic findings in 59 cases of horseshoe kidney are reviewed. Significant degrees of rotation are commoner and more pronounced in the left kidney in these cases than in the right kidney. This factor, rather than obliquity of the kidneys, is more likely to play a part in the development of upper urinary tract obstruction. Reversal of the normal direction of obliquity is not as common as is generally thought. The horseshoe kidney is, more often than not, mildly ectopic. Gross failure of ascent of the kidneys in the abdomen is uncommon. Evidence of pelvi-ureteric obstruction, especially hydronephrosis, occurred in just under half the cases. The reasons for this are discussed. The occurrence of other associated urinary tract anomalies, as well as acquired renal conditions, is considered."} {"id": "PMID:164317", "title": "Calcification in undifferentiated abdominal malignancies.", "content": "Four cases of undifferentiated abdominal malignancy are reported with a pattern of bizarre dystrophic calcifications. All of the cases had confusing histology and were long-term survivors; two being still alive. We feel that the radial, conglomerate masses of calcification, which do not conform to any organ, should suggest the diagnosis of an undifferentiated malignancy. The differential diagnosis and distinction from other causes of abdominal calcification is discussed.", "contents": "Calcification in undifferentiated abdominal malignancies. Four cases of undifferentiated abdominal malignancy are reported with a pattern of bizarre dystrophic calcifications. All of the cases had confusing histology and were long-term survivors; two being still alive. We feel that the radial, conglomerate masses of calcification, which do not conform to any organ, should suggest the diagnosis of an undifferentiated malignancy. The differential diagnosis and distinction from other causes of abdominal calcification is discussed."} {"id": "PMID:164318", "title": "Subcutaneous bone formation in the naevoid basal-cell carcinoma syndrome: normal urinary cyclic AMP response to parathyroid hormone infusion.", "content": "A patient with the naevoid basal-cell carcinoma syndrome had subcutaneous bone formation in the areas other than those occupied by the carcinomata. The patient did not show a significant phosphaturic response after parathyroid hormone infusion, but this extract produced a normal excretion of cyclic AMP. This proves that the subcutaneous bone does not signify an affinity to pseudo-hypoparathyroidism.", "contents": "Subcutaneous bone formation in the naevoid basal-cell carcinoma syndrome: normal urinary cyclic AMP response to parathyroid hormone infusion. A patient with the naevoid basal-cell carcinoma syndrome had subcutaneous bone formation in the areas other than those occupied by the carcinomata. The patient did not show a significant phosphaturic response after parathyroid hormone infusion, but this extract produced a normal excretion of cyclic AMP. This proves that the subcutaneous bone does not signify an affinity to pseudo-hypoparathyroidism."} {"id": "PMID:164333", "title": "[Malignant epithelial liver tumours in children (author's transl)].", "content": "Ten cases of malignant epithelial liver tumours in children, observed during a 12-year period (1962 to 1974), are described. They represent one of the largest groups of this neoplasm reported in the German-language medical literature. All histological types of malignant epithelial tumours were found among the ten cases. The prognosis of these tumours in children is poor, but it can be improved by modern therapeutic methods. Once the diagnosis has been established histologically (which may be difficult), radical surgery is essential, but to be successful early diagnosis is needed. Judged by optimal results of treatment this personal series constitutes a negative selection.", "contents": "[Malignant epithelial liver tumours in children (author's transl)]. Ten cases of malignant epithelial liver tumours in children, observed during a 12-year period (1962 to 1974), are described. They represent one of the largest groups of this neoplasm reported in the German-language medical literature. All histological types of malignant epithelial tumours were found among the ten cases. The prognosis of these tumours in children is poor, but it can be improved by modern therapeutic methods. Once the diagnosis has been established histologically (which may be difficult), radical surgery is essential, but to be successful early diagnosis is needed. Judged by optimal results of treatment this personal series constitutes a negative selection."} {"id": "PMID:164334", "title": "[Long-term treatment of hyperlipoproteinaemia, types IIa and IIb, with etiroxate (author's transl)].", "content": "A synthetic thyroxine derviative, etiroxate (DL-alpha-methyl-thyroxine-ethylester-CG 635) was administered to 40 patients with type IIa and 19 with type IIb hyperlipoproteinaemia for up to 390 days, 40 mg daily. It achieved a constant decrease in cholesterol of 83 mg/dl (23%) in type IIa and 64 mg/dl (18%) in types the alpha-and pre bata-lipoproteins fell when the concentration was greater than or equal to 200 mg/dl and greater than or equal to 140 mg/dl, respectively, both fractions rising when the initial concentration was below the mentioned figures. There were only slight side effects, such as gastric and autonomic nervous system symptoms. No statistically significant increase in anginal symptoms was found, even in patients with known coronary insufficiency.", "contents": "[Long-term treatment of hyperlipoproteinaemia, types IIa and IIb, with etiroxate (author's transl)]. A synthetic thyroxine derviative, etiroxate (DL-alpha-methyl-thyroxine-ethylester-CG 635) was administered to 40 patients with type IIa and 19 with type IIb hyperlipoproteinaemia for up to 390 days, 40 mg daily. It achieved a constant decrease in cholesterol of 83 mg/dl (23%) in type IIa and 64 mg/dl (18%) in types the alpha-and pre bata-lipoproteins fell when the concentration was greater than or equal to 200 mg/dl and greater than or equal to 140 mg/dl, respectively, both fractions rising when the initial concentration was below the mentioned figures. There were only slight side effects, such as gastric and autonomic nervous system symptoms. No statistically significant increase in anginal symptoms was found, even in patients with known coronary insufficiency."} {"id": "PMID:164335", "title": "[Activity of enzymes of galactose metabolism in so-called congenital cataract (author's transl)].", "content": "Activity of galactokinase (69 subjects) and galactose-1-phosphate uridyl transferase (92 subjects) were measured in haemolysed blood from children (predominantly of school age) with congenital cataract. chi2 tests, gene-frequency determination and metabolic-kinetic studies indicated that the changes in the lens in congenital cataract are partly due to a manifest or latent disorder of galactose metabolism, in particular a glactose-1-phosphate uridyl transferase defect.", "contents": "[Activity of enzymes of galactose metabolism in so-called congenital cataract (author's transl)]. Activity of galactokinase (69 subjects) and galactose-1-phosphate uridyl transferase (92 subjects) were measured in haemolysed blood from children (predominantly of school age) with congenital cataract. chi2 tests, gene-frequency determination and metabolic-kinetic studies indicated that the changes in the lens in congenital cataract are partly due to a manifest or latent disorder of galactose metabolism, in particular a glactose-1-phosphate uridyl transferase defect."} {"id": "PMID:164338", "title": "Formation of steroids by the pregnant mare. V. Metabolism of 14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone injected into the fetus.", "content": "A mixture of 1-14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone was injected into a horse fetus intramuscularly during laparotomy, after which maternal urine was collected for 4 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolysed and separated into phenolic and neutral fractions. From the phenolic fraction estrone, 17alpha-estradiol, equilin and equilenin were isolated. Only estrone and 17alpha-estradiol contained both 3H and 14C, while the ring B unsaturated estrogens contained only 14C. From the neutral fraction 14C-labeled 3beta-hydroxy-5alpha-pregnan-20-one, 5alpha-pregnane-3beta,20beta-diol and 5alpha-pregnan-3beta, 20alpha-diol were isolated. These results demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of isopentenylpyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis reported previously by us is occurring at a point after the formation of isopentenylpyrophosphate and prior to the formation of squalene.", "contents": "Formation of steroids by the pregnant mare. V. Metabolism of 14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone injected into the fetus. A mixture of 1-14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone was injected into a horse fetus intramuscularly during laparotomy, after which maternal urine was collected for 4 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolysed and separated into phenolic and neutral fractions. From the phenolic fraction estrone, 17alpha-estradiol, equilin and equilenin were isolated. Only estrone and 17alpha-estradiol contained both 3H and 14C, while the ring B unsaturated estrogens contained only 14C. From the neutral fraction 14C-labeled 3beta-hydroxy-5alpha-pregnan-20-one, 5alpha-pregnane-3beta,20beta-diol and 5alpha-pregnan-3beta, 20alpha-diol were isolated. These results demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of isopentenylpyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis reported previously by us is occurring at a point after the formation of isopentenylpyrophosphate and prior to the formation of squalene."} {"id": "PMID:164339", "title": "Effect of PGE1 and TSH on cAMP-dependent protein kinase activity in the thyroid.", "content": "PGE1, like TSH, can increase cAMP-dependent protein kinase activity in calf thyroid slices. The intracellular levels of cAMP produced by either of these agents alone appeared to correlate well with the degree of kinase activation. PG synthesis did not appear to be necessary for TSH action in this system, since indomethacin, and inhibitor of prostaglandin synthesis, did not alter either cAMP levels or kinase activity in slices incubated with TSH. Both the cAMP level and kinase activity rose when a submaximally effective dose of TSH was added to a maximal dose of PGE1. However, neither the cAMP levels nor the kinase activity produced by a maximal dose of TSH was affected by the addition of PGE1.", "contents": "Effect of PGE1 and TSH on cAMP-dependent protein kinase activity in the thyroid. PGE1, like TSH, can increase cAMP-dependent protein kinase activity in calf thyroid slices. The intracellular levels of cAMP produced by either of these agents alone appeared to correlate well with the degree of kinase activation. PG synthesis did not appear to be necessary for TSH action in this system, since indomethacin, and inhibitor of prostaglandin synthesis, did not alter either cAMP levels or kinase activity in slices incubated with TSH. Both the cAMP level and kinase activity rose when a submaximally effective dose of TSH was added to a maximal dose of PGE1. However, neither the cAMP levels nor the kinase activity produced by a maximal dose of TSH was affected by the addition of PGE1."} {"id": "PMID:164340", "title": "Effect of ACTH and histamine stress on serum corticosterone and adrenal cyclic AMP levels in immature rats.", "content": "Adrenal cAMP and plasma corticosterone levels were determined in pre-weanling rats subjected to treatment with either ACTH (50 mU/rat) or histamine dihydrochloride (0.2 mg/g body wt). ACTH injection elevated both serum corticosterone and adrenal cAMP levels on all days tested. However, the ACTH-induced elevation of adrenal cAMP and serum corticosterone both diminished steadily from day 2 to day 8 and then increased from day 8 to day 16. Histamine injection resulted in elevated serum corticosterone levels in a pattern similar to that of the corticosterone response to ACTH. However, histamine injection did not result in any significant increase in adrenal cAMP from day 2 to day 10. From day 12 to day 16 the adrenal cAMP concentration rose steadily in parallel with ther serum corticosterone levels. These results indicate: (1) that a functional, ACTH-sensitive adenyl cyclase system is present in the adrenal gland of the immature rat, (2) that the responsiveness of this system diminishes during the first postnatal week before returning to its previous 2-day-old capacity by day 16, and (3) that during the first few days after birth, histamine stress results in elevated serum corticosterone levels without elevating adrenal cAMP levels.", "contents": "Effect of ACTH and histamine stress on serum corticosterone and adrenal cyclic AMP levels in immature rats. Adrenal cAMP and plasma corticosterone levels were determined in pre-weanling rats subjected to treatment with either ACTH (50 mU/rat) or histamine dihydrochloride (0.2 mg/g body wt). ACTH injection elevated both serum corticosterone and adrenal cAMP levels on all days tested. However, the ACTH-induced elevation of adrenal cAMP and serum corticosterone both diminished steadily from day 2 to day 8 and then increased from day 8 to day 16. Histamine injection resulted in elevated serum corticosterone levels in a pattern similar to that of the corticosterone response to ACTH. However, histamine injection did not result in any significant increase in adrenal cAMP from day 2 to day 10. From day 12 to day 16 the adrenal cAMP concentration rose steadily in parallel with ther serum corticosterone levels. These results indicate: (1) that a functional, ACTH-sensitive adenyl cyclase system is present in the adrenal gland of the immature rat, (2) that the responsiveness of this system diminishes during the first postnatal week before returning to its previous 2-day-old capacity by day 16, and (3) that during the first few days after birth, histamine stress results in elevated serum corticosterone levels without elevating adrenal cAMP levels."} {"id": "PMID:164341", "title": "The hypothalamo-neurohypophysial complex in organ culture: effects of metabolic inhibitors, biologic and pharmacologic agents.", "content": "Organ cultures of the guinea pig hypothalamo-neurohypophysial complex synthesize the octapeptide hormone, vasopressin, a specific product of the neurosecretory cells of the supraoptic nucleus. Inhibitors of both protein and RNA synthesis (cycloheximide and bromotubercidin respectively) were found to block vasopressin biosynthesis. In the presence of bromotubercidin, the apparent half-time of decline in the rate of hormone biosynthesis was about 28 h. Colchicine inhibited the distal transport of vasopressin into the posterior pituitary. Ultrastructural studies on colchicine-treated cultures indicated the neuronal stalks were intact and that neurotubules were still present. The narcotic drug, levorphanol at 10-7 M and 10-9 M was found to inhibit RNA synthesis by 20 percent. At these concentrations it had no demonstrable effect on vasopressin synthesis. Cultures established from animals that had been rendered tolerant to narcotics also had no observable alterations in vasopressin biosynthesis, although the initial pituitary vasopressin content of these cultures was reduced by about 35 percent. Various pharmacologic and biologic compounds were tested for their effects on vasopressin biosynthesis in organ cultures. Dibutyryl cyclic AMP, estradiol-17beta, nicotine, nerve growth factor (NGF), and pineal extract all had no effects under the present experimental regimen. Medium conditioned by the presence of fetal hypothalami of 40-55 days gestation produced a 2-4 fold increase in vasopressin biosynthesis in cultures established from adult animals. Medium conditioned by fetal cerebral cortex, liver, or hypothalamic tissue from fetuses of less than 33 days gestation did not have this stimulatory effect.", "contents": "The hypothalamo-neurohypophysial complex in organ culture: effects of metabolic inhibitors, biologic and pharmacologic agents. Organ cultures of the guinea pig hypothalamo-neurohypophysial complex synthesize the octapeptide hormone, vasopressin, a specific product of the neurosecretory cells of the supraoptic nucleus. Inhibitors of both protein and RNA synthesis (cycloheximide and bromotubercidin respectively) were found to block vasopressin biosynthesis. In the presence of bromotubercidin, the apparent half-time of decline in the rate of hormone biosynthesis was about 28 h. Colchicine inhibited the distal transport of vasopressin into the posterior pituitary. Ultrastructural studies on colchicine-treated cultures indicated the neuronal stalks were intact and that neurotubules were still present. The narcotic drug, levorphanol at 10-7 M and 10-9 M was found to inhibit RNA synthesis by 20 percent. At these concentrations it had no demonstrable effect on vasopressin synthesis. Cultures established from animals that had been rendered tolerant to narcotics also had no observable alterations in vasopressin biosynthesis, although the initial pituitary vasopressin content of these cultures was reduced by about 35 percent. Various pharmacologic and biologic compounds were tested for their effects on vasopressin biosynthesis in organ cultures. Dibutyryl cyclic AMP, estradiol-17beta, nicotine, nerve growth factor (NGF), and pineal extract all had no effects under the present experimental regimen. Medium conditioned by the presence of fetal hypothalami of 40-55 days gestation produced a 2-4 fold increase in vasopressin biosynthesis in cultures established from adult animals. Medium conditioned by fetal cerebral cortex, liver, or hypothalamic tissue from fetuses of less than 33 days gestation did not have this stimulatory effect."} {"id": "PMID:164342", "title": "Biochemical comparison of estrogen receptors of the hamster hypothalamus and uterus.", "content": "Comparison of the soluble estradiol receptor proteins in the hypothalamus and uterus of the golden Syrian hamster revealed that both have sedimentation coefficients of 8S in a low ionic strength buffer and migrate similarly on analytical disc-gel electrophoresis in both 5% and 7% acrylamide gels. The competition of [3H]-17beta-estradiol binding by unlabeled estrogenic as well as nonestrogenic compounds was similar with the receptors present in the two tissues. The affinity constants for the hypothalamic and uterine receptors were 4.3 X 10-9M-1 and 1.6 X 10-10M-1, respectively; the number of binding sites when expressed on an equivalent protein basis (i.e. 1 mg/ml) was 0.18 X 10-10M and 3.1 X 10-10M, respectively. Identical amounts of soluble receptors with similar sedimentation characteristics were found in hypothalami from male and female animals gonadectomized 64 h prior to use. A titration of binding sites in the uteri of intact and ovariectomized animals revealed decreased binding in the supernatant preparation from intact animals, probably due to the presence of bound endogenous unlabeled hormone.", "contents": "Biochemical comparison of estrogen receptors of the hamster hypothalamus and uterus. Comparison of the soluble estradiol receptor proteins in the hypothalamus and uterus of the golden Syrian hamster revealed that both have sedimentation coefficients of 8S in a low ionic strength buffer and migrate similarly on analytical disc-gel electrophoresis in both 5% and 7% acrylamide gels. The competition of [3H]-17beta-estradiol binding by unlabeled estrogenic as well as nonestrogenic compounds was similar with the receptors present in the two tissues. The affinity constants for the hypothalamic and uterine receptors were 4.3 X 10-9M-1 and 1.6 X 10-10M-1, respectively; the number of binding sites when expressed on an equivalent protein basis (i.e. 1 mg/ml) was 0.18 X 10-10M and 3.1 X 10-10M, respectively. Identical amounts of soluble receptors with similar sedimentation characteristics were found in hypothalami from male and female animals gonadectomized 64 h prior to use. A titration of binding sites in the uteri of intact and ovariectomized animals revealed decreased binding in the supernatant preparation from intact animals, probably due to the presence of bound endogenous unlabeled hormone."} {"id": "PMID:164343", "title": "Role of adrenal 5alpha-reductase activity in determining the responsiveness of hypophysectomized rats to ACTH.", "content": "Studies were conducted to examine the contribution of adrenal 5alpha-reductase to the phenomenon of diminished adrenal \"responsiveness\" to ACTH after hypophysectomy in rats. Rats hypophysectomized for 1 week secreted small amounts of corticosterone (B), 5alpha-dihydrocorticosterone (DHB) and 3beta,5alpha-tetrahydrocorticosterone (R) acutely after ACTH. Adrenal reductase activity in vitro at that time was high. After replacement with ACTH for 24 h, B,DBH, and R secretion increased slightly. Reductase activity remained high. Treatment with ACTH for 2 days further stimulated secretion of DHB and R but not B. Reductase activity was unaffected. Enzyme activity declined at 3 days concomitant with a proportionately greater increase in B than DHB and R secretion. Only after 7 days of ACTH did B secretion exceed DHB and R output. At that time, reductase activity was still lower. The results establish the functional significance of 5alpha-reductase activity as a regulatory site for the action of ACTH in determining the composition of adrenocortical secretory products in hypophysectomized rats.", "contents": "Role of adrenal 5alpha-reductase activity in determining the responsiveness of hypophysectomized rats to ACTH. Studies were conducted to examine the contribution of adrenal 5alpha-reductase to the phenomenon of diminished adrenal \"responsiveness\" to ACTH after hypophysectomy in rats. Rats hypophysectomized for 1 week secreted small amounts of corticosterone (B), 5alpha-dihydrocorticosterone (DHB) and 3beta,5alpha-tetrahydrocorticosterone (R) acutely after ACTH. Adrenal reductase activity in vitro at that time was high. After replacement with ACTH for 24 h, B,DBH, and R secretion increased slightly. Reductase activity remained high. Treatment with ACTH for 2 days further stimulated secretion of DHB and R but not B. Reductase activity was unaffected. Enzyme activity declined at 3 days concomitant with a proportionately greater increase in B than DHB and R secretion. Only after 7 days of ACTH did B secretion exceed DHB and R output. At that time, reductase activity was still lower. The results establish the functional significance of 5alpha-reductase activity as a regulatory site for the action of ACTH in determining the composition of adrenocortical secretory products in hypophysectomized rats."} {"id": "PMID:164344", "title": "Insulin, prostaglandin E1, PHENYLISOPROPYLADENOSINE AND NICOTINIC ACID AS REGULATORS OF FAT CELL METABOLISM.", "content": "Insulin-stimulated glucose oxidation was enhanced by the addition of N6 (phenylisopropyl)adenosine (PIA), prostaglandin E1 (PGE1) or nicotinic acid during a 1-h incubation of small amounts 5-8 mg/ml) of rat fat cells. Basal lipolysis was appreciable if low numbers of fat cells were incubated per ml. Insulin inhibited basal lipolysis at 20 to 50 mugU/ml and abolished lipolysis of 100 mugU/ml was present over a l-h period. However PIA, PGE1 or nicotinic acid potentiated glucose oxidation due to the 100 mugU/ml dose of insulin indicating that these agents are not increasing glucose oxidation solely as a result of an inhibition of lipolysis. PIA, PGE1 and nicotinic acid acted synergistically with insulin in stimulating glucose oxidation and inhibiting lipolysis in the presence of norepinephrine. Insulin was unable to decrease basal cyclic AMP accumulation or the increase in cyclic AMP seen with norepinephrine and theophylline after various time periods (2 to 60 min) but PIA, PGE1 and nicotinic acid were able to inhibit cyclic AMP accumulation at all times tested.", "contents": "Insulin, prostaglandin E1, PHENYLISOPROPYLADENOSINE AND NICOTINIC ACID AS REGULATORS OF FAT CELL METABOLISM. Insulin-stimulated glucose oxidation was enhanced by the addition of N6 (phenylisopropyl)adenosine (PIA), prostaglandin E1 (PGE1) or nicotinic acid during a 1-h incubation of small amounts 5-8 mg/ml) of rat fat cells. Basal lipolysis was appreciable if low numbers of fat cells were incubated per ml. Insulin inhibited basal lipolysis at 20 to 50 mugU/ml and abolished lipolysis of 100 mugU/ml was present over a l-h period. However PIA, PGE1 or nicotinic acid potentiated glucose oxidation due to the 100 mugU/ml dose of insulin indicating that these agents are not increasing glucose oxidation solely as a result of an inhibition of lipolysis. PIA, PGE1 and nicotinic acid acted synergistically with insulin in stimulating glucose oxidation and inhibiting lipolysis in the presence of norepinephrine. Insulin was unable to decrease basal cyclic AMP accumulation or the increase in cyclic AMP seen with norepinephrine and theophylline after various time periods (2 to 60 min) but PIA, PGE1 and nicotinic acid were able to inhibit cyclic AMP accumulation at all times tested."} {"id": "PMID:164345", "title": "Cyclic 3', 5'-adenosine monophosphate levels in separated bone cells.", "content": "It has been shown that both parathyroid hormone (PTH) and calcitonin (CT) increase the concentration of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in skeletal tissue. Since these two hormones have opposing actions on bone resorption, it has been postulated that the cell types upon which the hormones act in skeletal tissue may be different. We have previously shown that osteoblasts and osteocytes contain adenylate cyclase responsive to both PTH and CT whereas the enzyme prepared from periosteum and marrow cells did not respond to either. To further examine the postulate, the effect of these hormones on the concentration of cyclic AMP was determined. Bovine PTH (5U/ml equal to 4.2 times 10-7M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, and osteocytes but not in marrow cells. Porcine CT (0.5 U/ml equal to 8.0 mug/ml approximately equal to 3.0 times 10-6M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, osteocytes, and marrow cells. Adenylate cyclase activity prepared from periosteum and marrow cells was re-examined using EGTA and DMSO to improve enzyme stability and activity. Wth these additions PTH (5 U/70 mul) increased activity of the preparation from periosteum, and CT (0.5 U/70 mul) increased activity from marrow cells and periosteum. These studies provide evidence that: 1) periosteum, osteoblasts, and osteocytes respond directly to both PTH and CT and 2) marrow cells respond to CT and not PTH.", "contents": "Cyclic 3', 5'-adenosine monophosphate levels in separated bone cells. It has been shown that both parathyroid hormone (PTH) and calcitonin (CT) increase the concentration of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in skeletal tissue. Since these two hormones have opposing actions on bone resorption, it has been postulated that the cell types upon which the hormones act in skeletal tissue may be different. We have previously shown that osteoblasts and osteocytes contain adenylate cyclase responsive to both PTH and CT whereas the enzyme prepared from periosteum and marrow cells did not respond to either. To further examine the postulate, the effect of these hormones on the concentration of cyclic AMP was determined. Bovine PTH (5U/ml equal to 4.2 times 10-7M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, and osteocytes but not in marrow cells. Porcine CT (0.5 U/ml equal to 8.0 mug/ml approximately equal to 3.0 times 10-6M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, osteocytes, and marrow cells. Adenylate cyclase activity prepared from periosteum and marrow cells was re-examined using EGTA and DMSO to improve enzyme stability and activity. Wth these additions PTH (5 U/70 mul) increased activity of the preparation from periosteum, and CT (0.5 U/70 mul) increased activity from marrow cells and periosteum. These studies provide evidence that: 1) periosteum, osteoblasts, and osteocytes respond directly to both PTH and CT and 2) marrow cells respond to CT and not PTH."} {"id": "PMID:164346", "title": "Effects of thyroid and ovaries on prolactin binding activity in rat liver.", "content": "125I-radiolabeled ovine prolactin (oPRL) binding activity was measured in microsomal membranes of liver tissue from intact, ovariectomized, ovariectomized-thyroidectomized, and ovariectomized-thyroidectomized rats injected with thyroxine (T4) or estradiol benzoate (EB). Thyroidectomy and ovariectomy each reduced PRL binding activity in liver tissue significantly. The combination of ovariectomy and thyroidectomy decreased PRL binding activity more than thyroidectomy or ovariectomy alone. Doses of 2.5 mug or 10 mug T4/100 g BW daily returned PRL binding activity in the thyroidectomized rats to intact control values, and in the ovariectomized-thyroidectomized rats to the ovariectomized values. A dose of 2 mug EB/rat increased PRL binding activity significantly in ovariectomized-thyroidectomized rats, and a combination of 2 mug EB and 2.5 mug T4/100E that of intact controls. Scatchard analysis showed that ovariectomy and thyroidectomy decreased the number of PRL binding sites in the liver as compared to those in intact controls or in ovariectomized-thyroidectomized rats treated with EB and T4. It is concluded that the thyroid and ovaries are important regulators of PRL binding activity in the liver of the rat.", "contents": "Effects of thyroid and ovaries on prolactin binding activity in rat liver. 125I-radiolabeled ovine prolactin (oPRL) binding activity was measured in microsomal membranes of liver tissue from intact, ovariectomized, ovariectomized-thyroidectomized, and ovariectomized-thyroidectomized rats injected with thyroxine (T4) or estradiol benzoate (EB). Thyroidectomy and ovariectomy each reduced PRL binding activity in liver tissue significantly. The combination of ovariectomy and thyroidectomy decreased PRL binding activity more than thyroidectomy or ovariectomy alone. Doses of 2.5 mug or 10 mug T4/100 g BW daily returned PRL binding activity in the thyroidectomized rats to intact control values, and in the ovariectomized-thyroidectomized rats to the ovariectomized values. A dose of 2 mug EB/rat increased PRL binding activity significantly in ovariectomized-thyroidectomized rats, and a combination of 2 mug EB and 2.5 mug T4/100E that of intact controls. Scatchard analysis showed that ovariectomy and thyroidectomy decreased the number of PRL binding sites in the liver as compared to those in intact controls or in ovariectomized-thyroidectomized rats treated with EB and T4. It is concluded that the thyroid and ovaries are important regulators of PRL binding activity in the liver of the rat."} {"id": "PMID:164347", "title": "Soluble and membrane-bound enzyme-active antigens of rat-liver lysosomes.", "content": "Secondary lysosomes were isolated from rat liver and separated into a soluble and a membrane fraction. Plasma membranes and microsomes were also isolated and antisera against the various fractions were prepared in rabbits. Lysosomal content and detergent-solubilized membrane fractions were analysed in two-dimensional immunoelectrophoresis (crossed immunoelectrophoresis). The immunoprecipitates were stained by histochemical procedures for different enzyme activities such as phosphatases, non-specific esterase, arylsulphatase, glycosidases and L-leucyl-beta-naphthylamidase. When lysosomal content was tested against its corresponding antiserum, 17 different precipitates could be seen. Most of the enzyme activities tested were shown to reside separately in one or a few precipitates each. In contrast, when the membrane extracts were investigated, a more polymorphic pattern of enzyme-active precipitates appeared. Thus, when lysosomal membrane extracts were reacted with homologous antiserum 11 precipitates with acid phosphatase activity were obtained. Several of the antigens were electrophoretically different and immunologically non-identical. As expected from the biology of secondary lysosomes, many of their antigens were also found in microsomes and/or plasma membranes, but several antigens unique for lysosomes were detected concomitantly. Closer analysis of these results indicated that several seemingly identical enzyme-active proteins occurred both in soluble and membrane-associated forms. However, while many of the membrane antigens expressed 2-4 different enzyme activities, only one activity was detected in individual precipitates of the lysosomal content. Thus, acid phosphatase activity was found together with esterase activity in three membrane-associated antigens. The precipitates formed by two of these also stained for arylsulphatase and nucleoside tri-, di- and monophosphatase activities. L-Leucyl-beta-naphthylamidase activity was found in one additional acid-phosphatase-active precipitate.", "contents": "Soluble and membrane-bound enzyme-active antigens of rat-liver lysosomes. Secondary lysosomes were isolated from rat liver and separated into a soluble and a membrane fraction. Plasma membranes and microsomes were also isolated and antisera against the various fractions were prepared in rabbits. Lysosomal content and detergent-solubilized membrane fractions were analysed in two-dimensional immunoelectrophoresis (crossed immunoelectrophoresis). The immunoprecipitates were stained by histochemical procedures for different enzyme activities such as phosphatases, non-specific esterase, arylsulphatase, glycosidases and L-leucyl-beta-naphthylamidase. When lysosomal content was tested against its corresponding antiserum, 17 different precipitates could be seen. Most of the enzyme activities tested were shown to reside separately in one or a few precipitates each. In contrast, when the membrane extracts were investigated, a more polymorphic pattern of enzyme-active precipitates appeared. Thus, when lysosomal membrane extracts were reacted with homologous antiserum 11 precipitates with acid phosphatase activity were obtained. Several of the antigens were electrophoretically different and immunologically non-identical. As expected from the biology of secondary lysosomes, many of their antigens were also found in microsomes and/or plasma membranes, but several antigens unique for lysosomes were detected concomitantly. Closer analysis of these results indicated that several seemingly identical enzyme-active proteins occurred both in soluble and membrane-associated forms. However, while many of the membrane antigens expressed 2-4 different enzyme activities, only one activity was detected in individual precipitates of the lysosomal content. Thus, acid phosphatase activity was found together with esterase activity in three membrane-associated antigens. The precipitates formed by two of these also stained for arylsulphatase and nucleoside tri-, di- and monophosphatase activities. L-Leucyl-beta-naphthylamidase activity was found in one additional acid-phosphatase-active precipitate."} {"id": "PMID:164348", "title": "Crystalline adenylate kinase from carp muscle.", "content": "1. The concentration of adenylate kinase in carp muscle is about 0.3 mg/g. An improved isolation procedure makes use of a dilute solution of the substrates, ATP and AMP, to elute the enzyme from a phosphocellulose column in overall yields of 60% before crystallization. By the hexokinase--pH-stat assay the specific activity is 3550 units/mg. The preparation has been found to be essentially homogeneous by dodecylsulfate gel electrophoresis, isoelectrofocusing and gel filtration. 2. The molecular weight has been determined to be 22000 by several methods. The absorbance of a 1% solution at 280 nm is 6.9 and the isoelectric point by electrofocusing is pH 5.9. 3. The crystals of carp adenylate kinase have the space group P4-1-22 or P4-3-22. 4. The amino acid composition has been determined. There is no tryptophan, no cystine. There is one amino acid residue each of cysteine and histidine which are at or close to the catalytic center. 5. Several peptides derived by tryptic hydrolysis have been isolated and identified with corresponding peptides of porcine adenylate kinase. Consideration is given to histidine and cysteine being a part of the active site.", "contents": "Crystalline adenylate kinase from carp muscle. 1. The concentration of adenylate kinase in carp muscle is about 0.3 mg/g. An improved isolation procedure makes use of a dilute solution of the substrates, ATP and AMP, to elute the enzyme from a phosphocellulose column in overall yields of 60% before crystallization. By the hexokinase--pH-stat assay the specific activity is 3550 units/mg. The preparation has been found to be essentially homogeneous by dodecylsulfate gel electrophoresis, isoelectrofocusing and gel filtration. 2. The molecular weight has been determined to be 22000 by several methods. The absorbance of a 1% solution at 280 nm is 6.9 and the isoelectric point by electrofocusing is pH 5.9. 3. The crystals of carp adenylate kinase have the space group P4-1-22 or P4-3-22. 4. The amino acid composition has been determined. There is no tryptophan, no cystine. There is one amino acid residue each of cysteine and histidine which are at or close to the catalytic center. 5. Several peptides derived by tryptic hydrolysis have been isolated and identified with corresponding peptides of porcine adenylate kinase. Consideration is given to histidine and cysteine being a part of the active site."} {"id": "PMID:164349", "title": "Premature induction of glucokinase in the neonatal rat by thyroid hormone.", "content": "1. It was shown that the development of liver glucokinase in the rat coincided with a peak in the levels of circulating thyroid hormone at about the 16th postnatal day. 2. Administration of thyroid inhibitors blocked the development of the enzyme and administration of thyroid hormone restored activity to normal levels. 3. Glucokinase could be induced prematurely as early as the 2nd postnatal day by the administration of thyroid hormone followed by daily injection of glucose (10 mg/g body weight). 4. Glucocorticoids and corticotropin failed to induce glucokinase activity prematurely. 5. The postnatal increase in circulating thyroid hormone levels together with increased intake of carbohydrate at weaning may be the normal physiological stimulus for induction of this enzyme.", "contents": "Premature induction of glucokinase in the neonatal rat by thyroid hormone. 1. It was shown that the development of liver glucokinase in the rat coincided with a peak in the levels of circulating thyroid hormone at about the 16th postnatal day. 2. Administration of thyroid inhibitors blocked the development of the enzyme and administration of thyroid hormone restored activity to normal levels. 3. Glucokinase could be induced prematurely as early as the 2nd postnatal day by the administration of thyroid hormone followed by daily injection of glucose (10 mg/g body weight). 4. Glucocorticoids and corticotropin failed to induce glucokinase activity prematurely. 5. The postnatal increase in circulating thyroid hormone levels together with increased intake of carbohydrate at weaning may be the normal physiological stimulus for induction of this enzyme."} {"id": "PMID:164350", "title": "The hormonal control of activity of skeletal muscle phosphorylase kinase. Amino-acid sequences at the two sites of action of adenosine-3':5'-monophosphate-dependent protein kinase.", "content": "Two tryptic phosphopeptides containing the sites on the alpha and beta subunits of phosphorylase kinase which are phosphorylated by protein kinase, dependent on adenosine 3':5'-monophosphate (cyclic AMP), have been isolated and their amino acid sequences have been determined. 32P-labelled phosphorylase kinase, containing 1.9 mol phosphate per mol enzyme, was digested with an equimolar quantity of trypsin for 2.5 min at pH 7.0, 20 degrees C. This treatment released nearly all the 32P radioactivity associated with the beta subunit as trichloroacetic-acid-soluble material. Only a small proportion of the 32P radioactivity associated with the alpha subunit was solubilised, the remainder being removed in the trichloroacetic acid pellet. The beta-subunit tryptic phosphopeptide was completely resolved from traces of the alpha-subunit phosphopeptide by gel filtration on Sephadex G-25. Further purification by peptide mapping separated the phosphopeptide into four components, each derived from the same nine-amino-acid segment of the betachain, which was found to possess the sequence: Gln-Ser-Gly-Ser(P)-Val-Ile-Tyr-Pro-Leu-Lys. The four components were produced by the partial cyclisation of the N-terminal glutaminyl residue, and by the presence of two alleles for the beta subunit in the rabbit population, which led to a valine-isoleucine ambiguity. The alpha-subunit phosphopeptide was liberated from the trichloroacetic acid pellet by redigestion with trypsin. It was the largest component in the digest which remained soluble in 5% trichloroacetic acid, and obtained in a highly purified form by a single filtration on Sephadex G-50. The peptide comprised 39 amino acids of which nine were serine and three were threonine residues. Only one residue, the serine at position three from the amino terminus, was phosphorylated. The amino-terminal sequence of the peptide was shown to be: Arg-Leu-Ser(P)-Ile-Ser-Thr-Glu-Ser-Glx-Pro-Asx-Gly. The sequences confirm the stoichiometry of the reaction and the absolute specificity of cyclic-AMP-dependent protein kinase for just two of the 200 serine residues in the enzyme. These results and an inspection of the rate of phosphorylation of a number of skeletal muscle proteins, including each enzyme of the glycolytic pathway, lead to the conclusion that cyclic-AMP-dependent protein kinase is an extremely specific enzyme. The molecular basis of this specificity is discussed.", "contents": "The hormonal control of activity of skeletal muscle phosphorylase kinase. Amino-acid sequences at the two sites of action of adenosine-3':5'-monophosphate-dependent protein kinase. Two tryptic phosphopeptides containing the sites on the alpha and beta subunits of phosphorylase kinase which are phosphorylated by protein kinase, dependent on adenosine 3':5'-monophosphate (cyclic AMP), have been isolated and their amino acid sequences have been determined. 32P-labelled phosphorylase kinase, containing 1.9 mol phosphate per mol enzyme, was digested with an equimolar quantity of trypsin for 2.5 min at pH 7.0, 20 degrees C. This treatment released nearly all the 32P radioactivity associated with the beta subunit as trichloroacetic-acid-soluble material. Only a small proportion of the 32P radioactivity associated with the alpha subunit was solubilised, the remainder being removed in the trichloroacetic acid pellet. The beta-subunit tryptic phosphopeptide was completely resolved from traces of the alpha-subunit phosphopeptide by gel filtration on Sephadex G-25. Further purification by peptide mapping separated the phosphopeptide into four components, each derived from the same nine-amino-acid segment of the betachain, which was found to possess the sequence: Gln-Ser-Gly-Ser(P)-Val-Ile-Tyr-Pro-Leu-Lys. The four components were produced by the partial cyclisation of the N-terminal glutaminyl residue, and by the presence of two alleles for the beta subunit in the rabbit population, which led to a valine-isoleucine ambiguity. The alpha-subunit phosphopeptide was liberated from the trichloroacetic acid pellet by redigestion with trypsin. It was the largest component in the digest which remained soluble in 5% trichloroacetic acid, and obtained in a highly purified form by a single filtration on Sephadex G-50. The peptide comprised 39 amino acids of which nine were serine and three were threonine residues. Only one residue, the serine at position three from the amino terminus, was phosphorylated. The amino-terminal sequence of the peptide was shown to be: Arg-Leu-Ser(P)-Ile-Ser-Thr-Glu-Ser-Glx-Pro-Asx-Gly. The sequences confirm the stoichiometry of the reaction and the absolute specificity of cyclic-AMP-dependent protein kinase for just two of the 200 serine residues in the enzyme. These results and an inspection of the rate of phosphorylation of a number of skeletal muscle proteins, including each enzyme of the glycolytic pathway, lead to the conclusion that cyclic-AMP-dependent protein kinase is an extremely specific enzyme. The molecular basis of this specificity is discussed."} {"id": "PMID:164351", "title": "Lipoprotein of the density 1.006-1.020 in the plasma of patients with type III hyperlipoproteinaemia in the postabsorptive state.", "content": "Using a rate zonal ultracentrifugal technique in 10 patients with type III hyperlipoproteinaemia, very low density lipoproteins (VLDL) (d less than 1.006, S(f) greater than 20), an intermediate lipoprotein density class with a S(f) range of 15 - 20 (Lp III), and low density lipoproteins (LDL) (S(f) 6 - 8) could be isolated from the plasma. The Lp III was found as a symmetrical peak between VLDL and LDL; its plasma concentration was 248 mg/100 ml plasma (mean), 92 - 469 mg/100 ml plasma (range); the Lp III/LDL ratio was 0.65 (mean), 0.25 - 2.3 (range); the chemical composition w/w was 35.8 percent total cholesterol, 19.3 percent triglycerides, 24.3 percent phospholipids, and 20.4 percent protein (mean). In agarose gel electrophoresis, the Lp III migrated faster than LDL, but slower than VLDL. By means of a double immunodiffusion technique and immunoelectrophoresis, apo-Lp B and apo-Lp C were detectable. In an angle head rotor at 1.4 x 10-8 g. min. Lp III can be separated from VLDL at a solvent density of 1.006, and from LDL at a density of 1.025. In the postabsorptive state in one patient with type I hyperlipoproteinaemia, five with type II and 20 with type IV, and in 50 healthy persons of both sexes, this Lp III peak was not found. The finding of a high concentration of Lp III and a rather low concentration of LDL in the plasma of patients with type III hyperlipoproteinaemia can be regarded as further evidence for an impaired catabolism of VLDL to LDL at Lp III (\"intermediate\" lipoprotein).", "contents": "Lipoprotein of the density 1.006-1.020 in the plasma of patients with type III hyperlipoproteinaemia in the postabsorptive state. Using a rate zonal ultracentrifugal technique in 10 patients with type III hyperlipoproteinaemia, very low density lipoproteins (VLDL) (d less than 1.006, S(f) greater than 20), an intermediate lipoprotein density class with a S(f) range of 15 - 20 (Lp III), and low density lipoproteins (LDL) (S(f) 6 - 8) could be isolated from the plasma. The Lp III was found as a symmetrical peak between VLDL and LDL; its plasma concentration was 248 mg/100 ml plasma (mean), 92 - 469 mg/100 ml plasma (range); the Lp III/LDL ratio was 0.65 (mean), 0.25 - 2.3 (range); the chemical composition w/w was 35.8 percent total cholesterol, 19.3 percent triglycerides, 24.3 percent phospholipids, and 20.4 percent protein (mean). In agarose gel electrophoresis, the Lp III migrated faster than LDL, but slower than VLDL. By means of a double immunodiffusion technique and immunoelectrophoresis, apo-Lp B and apo-Lp C were detectable. In an angle head rotor at 1.4 x 10-8 g. min. Lp III can be separated from VLDL at a solvent density of 1.006, and from LDL at a density of 1.025. In the postabsorptive state in one patient with type I hyperlipoproteinaemia, five with type II and 20 with type IV, and in 50 healthy persons of both sexes, this Lp III peak was not found. The finding of a high concentration of Lp III and a rather low concentration of LDL in the plasma of patients with type III hyperlipoproteinaemia can be regarded as further evidence for an impaired catabolism of VLDL to LDL at Lp III (\"intermediate\" lipoprotein)."} {"id": "PMID:164352", "title": "A potent depressant action of adenine derivatives on cerebral cortical neurones.", "content": "Adenosine and several adenine nucleotides depress the excitability of cerebral cortical neurones, including identified Betz cells. Cyclic 3',5'-adenosine monophosphate was a less effective depressant than various other adenine nucleotides, including cyclic 2',3'-adenosine monophosphate. Adenine and inosine had only weak depressant activity. An initial excitant action of ATP was observed on several neurones. This was succeeded by a depressant effect when the application of ATP was terminated.", "contents": "A potent depressant action of adenine derivatives on cerebral cortical neurones. Adenosine and several adenine nucleotides depress the excitability of cerebral cortical neurones, including identified Betz cells. Cyclic 3',5'-adenosine monophosphate was a less effective depressant than various other adenine nucleotides, including cyclic 2',3'-adenosine monophosphate. Adenine and inosine had only weak depressant activity. An initial excitant action of ATP was observed on several neurones. This was succeeded by a depressant effect when the application of ATP was terminated."} {"id": "PMID:164390", "title": "Voltage transients in neuronal dendritic trees.", "content": "An analytical method is outlined for calculating the passive voltage transient at each point in an extensively branched neuron model for arbitrary current injection at a single branch. The method is based on a convolution formula that employs the transient response function, the voltage response to an instantaneous pulse of current. For branching that satisfies Rall's equivalent cylinder constraint, the response function is determined explicitly. Voltage transients, for a brief current injected at a branch terminal, are evaluated at several locations to illustrate the attenuation and delay characteristics of passive spread. A comparison with the same transient input terminal input, the fraction of input charge dissipated by various branches in the neuron model is illustrated. These fractions are independent of the input time course. For transient synaptic conductance change at a single branch terminal, a numerical example demonstrates the nonlinear effect of reduced synaptic driving potential. The branch terminal synaptic input is compared with the same synaptic conductance input applied to the soma on the basis of excitatory postsynaptic potential amplitude at the soma and charge delivered to the soma.", "contents": "Voltage transients in neuronal dendritic trees. An analytical method is outlined for calculating the passive voltage transient at each point in an extensively branched neuron model for arbitrary current injection at a single branch. The method is based on a convolution formula that employs the transient response function, the voltage response to an instantaneous pulse of current. For branching that satisfies Rall's equivalent cylinder constraint, the response function is determined explicitly. Voltage transients, for a brief current injected at a branch terminal, are evaluated at several locations to illustrate the attenuation and delay characteristics of passive spread. A comparison with the same transient input terminal input, the fraction of input charge dissipated by various branches in the neuron model is illustrated. These fractions are independent of the input time course. For transient synaptic conductance change at a single branch terminal, a numerical example demonstrates the nonlinear effect of reduced synaptic driving potential. The branch terminal synaptic input is compared with the same synaptic conductance input applied to the soma on the basis of excitatory postsynaptic potential amplitude at the soma and charge delivered to the soma."} {"id": "PMID:164391", "title": "Motoneuron dendrites: role in synaptic integration.", "content": "Dendrites constitute over 80 per cent of the receptive surface area in cat motoneurons. Calculations based on matched electrical and gemoetrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on the dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties.", "contents": "Motoneuron dendrites: role in synaptic integration. Dendrites constitute over 80 per cent of the receptive surface area in cat motoneurons. Calculations based on matched electrical and gemoetrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on the dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties."} {"id": "PMID:164392", "title": "Tumour cell destruction by macrophages from conventional animals.", "content": "Peritoneal exudate cells (PEC) from conventional donors displayed in vitro the cytotocix effects on the rat sarcoma cell lines LWI3K2, LW13K3, LW13K4 and RSL but they were not cytotoxic to fibroblasts derived from normal rats of the same strains. PEC were also cytotoxic to human urinary bladder carcinoma cells (T-24) grown in vitro. Cytotoxicity was detectable already at the effector to target cell ratio of 1 : 1, and the effector cells from syngeneic, allogeneic and xenogeneic donors were equally effective. The cytotoxic effect was apparently exerted by macrophages because the addition of lymphocytes from PEC donors did not change the target cells. The addition of serum from PEC donors to a mixture of target and effector cells protected the tumour cells from the destruction by macrophages. Cytotoxicity was blocked by serum from all PEC donors tested (syngeneic, allogeneic and xenogeneic with regard to the target cells) but not by foetal calf serum.", "contents": "Tumour cell destruction by macrophages from conventional animals. Peritoneal exudate cells (PEC) from conventional donors displayed in vitro the cytotocix effects on the rat sarcoma cell lines LWI3K2, LW13K3, LW13K4 and RSL but they were not cytotoxic to fibroblasts derived from normal rats of the same strains. PEC were also cytotoxic to human urinary bladder carcinoma cells (T-24) grown in vitro. Cytotoxicity was detectable already at the effector to target cell ratio of 1 : 1, and the effector cells from syngeneic, allogeneic and xenogeneic donors were equally effective. The cytotoxic effect was apparently exerted by macrophages because the addition of lymphocytes from PEC donors did not change the target cells. The addition of serum from PEC donors to a mixture of target and effector cells protected the tumour cells from the destruction by macrophages. Cytotoxicity was blocked by serum from all PEC donors tested (syngeneic, allogeneic and xenogeneic with regard to the target cells) but not by foetal calf serum."} {"id": "PMID:164398", "title": "Persisting enhanced proinsulin-insulin and protein biosynthesis (3H-leucine incorporation) by pancreatic islets of the rat after glucose exposure.", "content": "Pancreatic islets isolated from rats infused with glucose for twenty-four hours incorporated 3H-leucine into protein at higher rates than islets isolated from normoglycemic rats. Incorporation into proinsulin-insulin showed a thirteenfold increase. The effect on other islet proteins was fourfold. Exposure of islets from normoglycemic rats to high glucose in vitro for twenty and ninety minutes and subsequent incubation with 3H-leucine at low glucose showed a twofold and fivefold increase in proinsulin biosynthesis. In the in vitro system pre-exposure of the islets to mannose and dibutyryl-cyclic AMP induced a much smaller increase in proinsulin biosyntheses.", "contents": "Persisting enhanced proinsulin-insulin and protein biosynthesis (3H-leucine incorporation) by pancreatic islets of the rat after glucose exposure. Pancreatic islets isolated from rats infused with glucose for twenty-four hours incorporated 3H-leucine into protein at higher rates than islets isolated from normoglycemic rats. Incorporation into proinsulin-insulin showed a thirteenfold increase. The effect on other islet proteins was fourfold. Exposure of islets from normoglycemic rats to high glucose in vitro for twenty and ninety minutes and subsequent incubation with 3H-leucine at low glucose showed a twofold and fivefold increase in proinsulin biosynthesis. In the in vitro system pre-exposure of the islets to mannose and dibutyryl-cyclic AMP induced a much smaller increase in proinsulin biosyntheses."} {"id": "PMID:164399", "title": "Pyrimidine biosynthetic enzymes in rat intestine after small bowel resection.", "content": "After small bowel resection in the rat, mucosal hyperplasia and an increase in nucleic acid synthesis and cell proliferation occur in remaining small intestine. Male Sprague-Dawley rate underwent resection of 50 cm of proximal or distal intestine or sham operation. One month and 6 months after surgery, aspartate transcarbamylase, dihydroorotase, and uridine kinase were assayed in whole mucosa, and in some instances, in crypt mucosa ffrom the remaining intestinal segment. In control bowel, enzyme activity was significantly greater proximal compared with distal segments. One month after proximal or distal resection, mucosal enzyme activity per cm of gut was greater in the remnant bowel compared with controls. There was no such difference at 6 months. Specific enzyme activity of whole mucosa did not increase after resection because the assay was influenced by the disproportionately large contribution of villous protein. Specific enzyme activity (including thymidine kinase) of isolated crypt mucosa was significantly increased 1 month after distal resection. In addition, [3H]thymidine uptake into DNA of crypt mucosa from proximal remnants was also significantly increased. These results indicate that after small bowel resection, the enzymes of pryimidine biosynthesis increase in remaining bowel and parallel the accelerated rate of cell proliferation.", "contents": "Pyrimidine biosynthetic enzymes in rat intestine after small bowel resection. After small bowel resection in the rat, mucosal hyperplasia and an increase in nucleic acid synthesis and cell proliferation occur in remaining small intestine. Male Sprague-Dawley rate underwent resection of 50 cm of proximal or distal intestine or sham operation. One month and 6 months after surgery, aspartate transcarbamylase, dihydroorotase, and uridine kinase were assayed in whole mucosa, and in some instances, in crypt mucosa ffrom the remaining intestinal segment. In control bowel, enzyme activity was significantly greater proximal compared with distal segments. One month after proximal or distal resection, mucosal enzyme activity per cm of gut was greater in the remnant bowel compared with controls. There was no such difference at 6 months. Specific enzyme activity of whole mucosa did not increase after resection because the assay was influenced by the disproportionately large contribution of villous protein. Specific enzyme activity (including thymidine kinase) of isolated crypt mucosa was significantly increased 1 month after distal resection. In addition, [3H]thymidine uptake into DNA of crypt mucosa from proximal remnants was also significantly increased. These results indicate that after small bowel resection, the enzymes of pryimidine biosynthesis increase in remaining bowel and parallel the accelerated rate of cell proliferation."} {"id": "PMID:164403", "title": "Response of camels to intradermal inoculation with smallpox and camelpox viruses.", "content": "Young camels were inoculated intradermally with either camelpox or smallpox virus and the courses of infection, including serological response, were compared. Camelpox virus was highly infectious; generalized disease resulted which was transmitted naturally to contact animals. Smallpox virus produced only transient lesions at the inoculation site and a less marked serological response. Nevertheless, the camels inoculated with smallpox virus subsequently resisted a severe challenge with camelpox virus, and the possibility that limited replication of smallpox virus took place is discussed. The differences demonstrated between the behavior of the vituses is discussed in the light of their otherwise close relationship and the limited information available about camelpox infections in man.", "contents": "Response of camels to intradermal inoculation with smallpox and camelpox viruses. Young camels were inoculated intradermally with either camelpox or smallpox virus and the courses of infection, including serological response, were compared. Camelpox virus was highly infectious; generalized disease resulted which was transmitted naturally to contact animals. Smallpox virus produced only transient lesions at the inoculation site and a less marked serological response. Nevertheless, the camels inoculated with smallpox virus subsequently resisted a severe challenge with camelpox virus, and the possibility that limited replication of smallpox virus took place is discussed. The differences demonstrated between the behavior of the vituses is discussed in the light of their otherwise close relationship and the limited information available about camelpox infections in man."} {"id": "PMID:164404", "title": "Determination of toxin-induced leakage of different-size nucleotides through the plasma membrane of human diploid fibroblasts.", "content": "Human diploid lung fibroblasts were treated with cytolytic bacterial toxins and the nature of the membrane damage was investigated. [3H] uridine was used for differential labeling of cytoplasmic components of small or large molecular size. Two principal size categories were achieved by labeling the fibroblasts in either early growth phase or stationary phase, a high-molecular weight ribonucleic acid label and a low-molecular-weight nucleotide label. The size of the labeled molecules was determined by perchloric acid precipitation and gel chromatography. Leakage of labeled molecules of different size indicated the size of the \"functional pores\" in the plasma membrane caused by the test substance. The nonionic detergent Triton X-100 produced large functional pores in the fibroblast membrane as evidenced by rapid leakage of both large and small labeled molecules. Theta-toxin from Clostridium perfringens and the polyene antibiotic filipin both gave rise to considerably small functional pores in the plasma membrane. Although small molecules easily passed the treated membrane, large molecules could not escape from the cells even after prolonged treatment with these substances or by increasing their concentration. By the contrast, the leakage profiles obtained with melittin from bee venom or with delta-toxin from Staphylococcus aureus in each case suggested the formation initially of pores of intermediate size that increased upon prolonged incubation or when higher concentrations were used.", "contents": "Determination of toxin-induced leakage of different-size nucleotides through the plasma membrane of human diploid fibroblasts. Human diploid lung fibroblasts were treated with cytolytic bacterial toxins and the nature of the membrane damage was investigated. [3H] uridine was used for differential labeling of cytoplasmic components of small or large molecular size. Two principal size categories were achieved by labeling the fibroblasts in either early growth phase or stationary phase, a high-molecular weight ribonucleic acid label and a low-molecular-weight nucleotide label. The size of the labeled molecules was determined by perchloric acid precipitation and gel chromatography. Leakage of labeled molecules of different size indicated the size of the \"functional pores\" in the plasma membrane caused by the test substance. The nonionic detergent Triton X-100 produced large functional pores in the fibroblast membrane as evidenced by rapid leakage of both large and small labeled molecules. Theta-toxin from Clostridium perfringens and the polyene antibiotic filipin both gave rise to considerably small functional pores in the plasma membrane. Although small molecules easily passed the treated membrane, large molecules could not escape from the cells even after prolonged treatment with these substances or by increasing their concentration. By the contrast, the leakage profiles obtained with melittin from bee venom or with delta-toxin from Staphylococcus aureus in each case suggested the formation initially of pores of intermediate size that increased upon prolonged incubation or when higher concentrations were used."} {"id": "PMID:164405", "title": "Cytomegalovirus infection in a volunteer blood donor population.", "content": "Among 223 volunteer blood donors who were studied for evidence of cytomegalovirus (CMV) infection, 58 percent had complement-fixing antibody and 59 percent had indirect hemagglutinating antibody to CMV. No virus was isolated from any donor's washed leukocytes or leukocyte-rich plasma in fibroblast monolayer culture. In seven asymptomatic donors (3 percent), CMV was recovered from urine cultures obtained at the time of blood donation. However, at the time of reexamination, viruria was no longer present and serum antibody titers had not changed. In the three patients studied who received blood from three of the cytomegaloviruric donors, serological evidence of CMV infection developed (fourfold or greater indirect hemagglutinating antibody rise), and one recipient also developed cytomegaloviruria; no illnesses was associated with these infections. Further study is needed to establish that the detection of viruria in donors may identify potentially infective blood.", "contents": "Cytomegalovirus infection in a volunteer blood donor population. Among 223 volunteer blood donors who were studied for evidence of cytomegalovirus (CMV) infection, 58 percent had complement-fixing antibody and 59 percent had indirect hemagglutinating antibody to CMV. No virus was isolated from any donor's washed leukocytes or leukocyte-rich plasma in fibroblast monolayer culture. In seven asymptomatic donors (3 percent), CMV was recovered from urine cultures obtained at the time of blood donation. However, at the time of reexamination, viruria was no longer present and serum antibody titers had not changed. In the three patients studied who received blood from three of the cytomegaloviruric donors, serological evidence of CMV infection developed (fourfold or greater indirect hemagglutinating antibody rise), and one recipient also developed cytomegaloviruria; no illnesses was associated with these infections. Further study is needed to establish that the detection of viruria in donors may identify potentially infective blood."} {"id": "PMID:164406", "title": "Lysis of herpesvirus-infected cells by immune spleen cells.", "content": "Spleen cells from herpes simplex-infected mice have been shown to lyse 51Cr-labeled virus-infected target cells. The cell-mediated lysis was shown to be antibody dependent but not involving adherent cells. Lysis of infected cells by this mechanism may be one form of host defense in infection by some viruses.", "contents": "Lysis of herpesvirus-infected cells by immune spleen cells. Spleen cells from herpes simplex-infected mice have been shown to lyse 51Cr-labeled virus-infected target cells. The cell-mediated lysis was shown to be antibody dependent but not involving adherent cells. Lysis of infected cells by this mechanism may be one form of host defense in infection by some viruses."} {"id": "PMID:164407", "title": "Bovine parainfluenza type 3 virus infection: virus replication in bovine embryonic cell cultures and virion separation by rate-zonal centrifugation.", "content": "Replicative sequences of a bovine strain of parainfluenza type 3 virus in bovine embryonic kidney and spleen cell cultures were investigated by light and fluorescence microscopy and by ultrathin section and negative-contrast electron microscopy. Observations from light and fluorescence microscopy showed that intracytoplasmic inclusions were detected as small granules surrounding the nuclei of more than 90 percent of the cell population by day 2 postinoculation. With the increase of postexposure times, these inclusions coalesced into larger bodies which occupied large portions of the cell. Ultrastructurally, the first sign of virus development was the appearance of aggregates of viral nucleocapsids in the vicinity of the nucleus. With the concomitant accumulation of viral nucleocapsids in the cytoplasm, the virus maturation was expressed by budding processes through the cell membrane into round, oval, or elongated forms. Eosinophilic inclusions were demonstrable in many mitotic cells. Ultrastructurally, these cells were observed to produce virus particles by a process identical to that of resting cells. Virions, prepared from infected culture fluid and negatively stained, appeared to be pleomorphic and their diameter ranged from 200 to 600 mm. The virions were separated, by rate-zonal centrifugation, into two subclasses in a sucrose gradient (15 to 60 percent, wt/wt). The slowly sedimenting virions had a density approximately 1.20 gm/cm3 and an average size of 200 nm in diameter, whereas the faster-sedimenting virions had a density of 1.24 gm/cm3 and average diameter of 400 nm.", "contents": "Bovine parainfluenza type 3 virus infection: virus replication in bovine embryonic cell cultures and virion separation by rate-zonal centrifugation. Replicative sequences of a bovine strain of parainfluenza type 3 virus in bovine embryonic kidney and spleen cell cultures were investigated by light and fluorescence microscopy and by ultrathin section and negative-contrast electron microscopy. Observations from light and fluorescence microscopy showed that intracytoplasmic inclusions were detected as small granules surrounding the nuclei of more than 90 percent of the cell population by day 2 postinoculation. With the increase of postexposure times, these inclusions coalesced into larger bodies which occupied large portions of the cell. Ultrastructurally, the first sign of virus development was the appearance of aggregates of viral nucleocapsids in the vicinity of the nucleus. With the concomitant accumulation of viral nucleocapsids in the cytoplasm, the virus maturation was expressed by budding processes through the cell membrane into round, oval, or elongated forms. Eosinophilic inclusions were demonstrable in many mitotic cells. Ultrastructurally, these cells were observed to produce virus particles by a process identical to that of resting cells. Virions, prepared from infected culture fluid and negatively stained, appeared to be pleomorphic and their diameter ranged from 200 to 600 mm. The virions were separated, by rate-zonal centrifugation, into two subclasses in a sucrose gradient (15 to 60 percent, wt/wt). The slowly sedimenting virions had a density approximately 1.20 gm/cm3 and an average size of 200 nm in diameter, whereas the faster-sedimenting virions had a density of 1.24 gm/cm3 and average diameter of 400 nm."} {"id": "PMID:164408", "title": "Bovine parainfluenza type 3 virus infection: ultrastructural aspects of viral pathogenesis in the bovine respiratory tract.", "content": "After aerosolization of a bovine strain of parainfluenza type 3 virus, the pathogenesis of the virus was followed from the trachea to the bronchioalveolar compartments of the lung of colostrum-free calves and of conventionally reared calves during a 5- to 12-day postexposure interval. By tissue titration, plaque assay, and electron microscopy, it was found that virus infection could be established in colostrum-free calves as well as in conventionally reared calves, even though sequential changes of virus replication were observed mainly in the infected colostrum-free calves during the 5- to 6-day postexposure periods. Electron microscopy demonstrations of (i) aggregates of viral nucleocapsids in the cytoplasm, (ii) alterations of cilia and basal bodies, (iii) dissolution of cytoplasmic membranes, and (iv) the shedding of virus into luminal spaces confirmed that epithelial cells of the respiratory tract were the primary target cells for the virus replication leading to cell destruction. These observations revealed further that productive infection was more efficient in the bronchioalveolar regions than in the tracheal regions, although large aggregates of viral nucleocapsids and destructive changes were more pronounced in the tracheal epithelium. The finding that parainfluenza type 3 virus replicates in the alveolar type II cells suggests that changes in surfactant production may occur during the peak of infection of these cells. The demonstration of virus budding through the basement membrane of small bronchioles and the presence of virus particles in the interstitial regions imply that one of the host defense lines, the basement membrane, may be impaired by virus invasion.", "contents": "Bovine parainfluenza type 3 virus infection: ultrastructural aspects of viral pathogenesis in the bovine respiratory tract. After aerosolization of a bovine strain of parainfluenza type 3 virus, the pathogenesis of the virus was followed from the trachea to the bronchioalveolar compartments of the lung of colostrum-free calves and of conventionally reared calves during a 5- to 12-day postexposure interval. By tissue titration, plaque assay, and electron microscopy, it was found that virus infection could be established in colostrum-free calves as well as in conventionally reared calves, even though sequential changes of virus replication were observed mainly in the infected colostrum-free calves during the 5- to 6-day postexposure periods. Electron microscopy demonstrations of (i) aggregates of viral nucleocapsids in the cytoplasm, (ii) alterations of cilia and basal bodies, (iii) dissolution of cytoplasmic membranes, and (iv) the shedding of virus into luminal spaces confirmed that epithelial cells of the respiratory tract were the primary target cells for the virus replication leading to cell destruction. These observations revealed further that productive infection was more efficient in the bronchioalveolar regions than in the tracheal regions, although large aggregates of viral nucleocapsids and destructive changes were more pronounced in the tracheal epithelium. The finding that parainfluenza type 3 virus replicates in the alveolar type II cells suggests that changes in surfactant production may occur during the peak of infection of these cells. The demonstration of virus budding through the basement membrane of small bronchioles and the presence of virus particles in the interstitial regions imply that one of the host defense lines, the basement membrane, may be impaired by virus invasion."} {"id": "PMID:164409", "title": "Comparative studies of Visna and Maedi viruses as antigens.", "content": "Rabbits were immunized with purified visna and maedi viruses, using complete Freund adjuvant, in footpad and intramuscular sites. The resulting antisera and their isolated immunoglobulin G (IgG) and M (IgM) classes were evaluated by tanned-cell passive hemagglutination (PHA), complement fixation, gel diffusion, and virus neutralization tests. Early, intermediate, and late bleedings showed increasingly high antibody activities by the PHA, complement fixation, and gel diffusion tests. The activities were associated mainly with the IgG class, although low, but significant activities were also found in the IgM class, as detected by PHA and complement fixation tests. Both antibody classes appeared at the same time during the course of immunization. The viruses, when tested against specific rabbit anti-visna and anti-maedi sera in gel diffusion tests, showed the presence of one to two precipitin lines depending upon the antibody concentration of the sera. A low amount of neutralizing activity was demonstrated in late bleedings but was not seen in earlier bleedings. The neutralizing activity against visna virus in immunized rabbit sera was found to be associated only with the IgG class. Visna and maedi viruses appeared to be immunologically identical when examined in gel diffusion tests and showed the same degree of inhibition when compared in passive hemagglutination inhibition test using antisera made specific for each virus.", "contents": "Comparative studies of Visna and Maedi viruses as antigens. Rabbits were immunized with purified visna and maedi viruses, using complete Freund adjuvant, in footpad and intramuscular sites. The resulting antisera and their isolated immunoglobulin G (IgG) and M (IgM) classes were evaluated by tanned-cell passive hemagglutination (PHA), complement fixation, gel diffusion, and virus neutralization tests. Early, intermediate, and late bleedings showed increasingly high antibody activities by the PHA, complement fixation, and gel diffusion tests. The activities were associated mainly with the IgG class, although low, but significant activities were also found in the IgM class, as detected by PHA and complement fixation tests. Both antibody classes appeared at the same time during the course of immunization. The viruses, when tested against specific rabbit anti-visna and anti-maedi sera in gel diffusion tests, showed the presence of one to two precipitin lines depending upon the antibody concentration of the sera. A low amount of neutralizing activity was demonstrated in late bleedings but was not seen in earlier bleedings. The neutralizing activity against visna virus in immunized rabbit sera was found to be associated only with the IgG class. Visna and maedi viruses appeared to be immunologically identical when examined in gel diffusion tests and showed the same degree of inhibition when compared in passive hemagglutination inhibition test using antisera made specific for each virus."} {"id": "PMID:164410", "title": "Lanthanum inhibition of Vibrio cholerae and Escherichia coli enterotoxin-induced enterosorption and its effects on intestinal mucosa cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels.", "content": "Several trivalent cations, including lanthanum (La3+), inhibited the secretion (enterosorption) induced by the enterotoxins of Vibrio cholerae and Escherichia coli in the rabbit ileum in vivo. High concentrations (greater than 10 mM) of La3+ were required to inhibit cholera enterotoxin (CE)-induced enterosorption, probably because of the adsorption of the La3+ often potentiated the CE-induced enterosorption. If luminal La3+ exposure followed CE exposure, some recovery of the enterosorptive response was observed. The longer the lag between the CE exposure and the La3+ exposure, the greater was the recovery of the enterosorptive response. Lanthanum inhibited HCO3- secretion more than Cl- secretion. By altering the luminal fluid pH at the time of La3+ exposure, it was found that La3+ was adsorbed to negatively charged luminal sites, having an apparent pK between 2.5 and 3.0. Although La3+ antagonized the enterosorptive response to CE, it mimicked rather than antagonized the cyclic adenosine 3',5'-monophosphate elevation and cyclic guanosine 3',5'-monophosphate depression induced by the toxin. It is therefore concluded that the La3+ inhibition of the CE-induced enterosorption must have occurred at a site following the generation of the cyclic nucleotides. Cholera enterotoxin caused complex time-dependent changes in the mucosal cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels, as revealed by studying tissue cyclic adenosine 3',5'-monophosphate/cyclic guanosine 3',5'-monophosphate ratios. The possible roles these two cyclic nucleotides may play in the pathogenesis of the cholera diarrhea are discussed.", "contents": "Lanthanum inhibition of Vibrio cholerae and Escherichia coli enterotoxin-induced enterosorption and its effects on intestinal mucosa cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels. Several trivalent cations, including lanthanum (La3+), inhibited the secretion (enterosorption) induced by the enterotoxins of Vibrio cholerae and Escherichia coli in the rabbit ileum in vivo. High concentrations (greater than 10 mM) of La3+ were required to inhibit cholera enterotoxin (CE)-induced enterosorption, probably because of the adsorption of the La3+ often potentiated the CE-induced enterosorption. If luminal La3+ exposure followed CE exposure, some recovery of the enterosorptive response was observed. The longer the lag between the CE exposure and the La3+ exposure, the greater was the recovery of the enterosorptive response. Lanthanum inhibited HCO3- secretion more than Cl- secretion. By altering the luminal fluid pH at the time of La3+ exposure, it was found that La3+ was adsorbed to negatively charged luminal sites, having an apparent pK between 2.5 and 3.0. Although La3+ antagonized the enterosorptive response to CE, it mimicked rather than antagonized the cyclic adenosine 3',5'-monophosphate elevation and cyclic guanosine 3',5'-monophosphate depression induced by the toxin. It is therefore concluded that the La3+ inhibition of the CE-induced enterosorption must have occurred at a site following the generation of the cyclic nucleotides. Cholera enterotoxin caused complex time-dependent changes in the mucosal cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels, as revealed by studying tissue cyclic adenosine 3',5'-monophosphate/cyclic guanosine 3',5'-monophosphate ratios. The possible roles these two cyclic nucleotides may play in the pathogenesis of the cholera diarrhea are discussed."} {"id": "PMID:164411", "title": "Characterization of enterotoxin purified from Clostridium perfringens type C.", "content": "Enterotoxin produced by a sporulating culture of Clostridium perfringens type C, which had been isolated from a case of severe necrotic enteritis, was purified. The molecular weight was estimated to be 36,000 by gel chromatography on Sephadex G-100 and 33,400 by ultracentrifugation. The sedimentation coefficient S20,W was 2.92. The toxin protein exhibited unusual behavior on sodium dodecyl sulfate gels, and toxin aggregates having molecular weights of 68,000, 85,000, 105,000, and 140,000 were obtained. The purified enterotoxin often separated, apparently due to slight charge differences, into two protein bands on 7% polyacrylamide gels. Electrofocusing of enterotoxin on polyacrylamide gels gave an approximate isoelectric point of 4.3, with the enterotoxin being fractionated into four distinct protein bands. The specific toxicity of the enterotoxin was about 1,900 mouse mean lethal doses per mg of calculated nitrogen. The data obtained indicate that the enterotoxin from C. perfringens type C is identical in most respects to that obtained from type A strains. Whether or not this toxin plays a role in the necrotic enteritis caused by type C strains is unknown at present.", "contents": "Characterization of enterotoxin purified from Clostridium perfringens type C. Enterotoxin produced by a sporulating culture of Clostridium perfringens type C, which had been isolated from a case of severe necrotic enteritis, was purified. The molecular weight was estimated to be 36,000 by gel chromatography on Sephadex G-100 and 33,400 by ultracentrifugation. The sedimentation coefficient S20,W was 2.92. The toxin protein exhibited unusual behavior on sodium dodecyl sulfate gels, and toxin aggregates having molecular weights of 68,000, 85,000, 105,000, and 140,000 were obtained. The purified enterotoxin often separated, apparently due to slight charge differences, into two protein bands on 7% polyacrylamide gels. Electrofocusing of enterotoxin on polyacrylamide gels gave an approximate isoelectric point of 4.3, with the enterotoxin being fractionated into four distinct protein bands. The specific toxicity of the enterotoxin was about 1,900 mouse mean lethal doses per mg of calculated nitrogen. The data obtained indicate that the enterotoxin from C. perfringens type C is identical in most respects to that obtained from type A strains. Whether or not this toxin plays a role in the necrotic enteritis caused by type C strains is unknown at present."} {"id": "PMID:164412", "title": "Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination.", "content": "An unusual biphasic central nervous system disease developed in 3-week-old Swiss outbred mice after intracerebral inoculation of the DA strain of Theiler's murine encephalomyelitis virus. Nine to 20 days postinfection 86% of mice became paralyzed, and approximately one-half of these animals survived. During this period neuronal necrosis and microglial proliferation were seen in thalamus, brainstem, and spinal cord. There was an initial phase of virus growth in spinal cord followed by persistent infection at a lower concentration. Virus antigen was readily found in the cytoplasm of neurons by immunofluorescent staining early in the course of infection, whereas after 30 days there was a paucity of cells containing virus antigen which were present only in the spinal cord white matter. Between 1 and 5 months, an intense mononuclear inflammatory cell lesion evolved in the spinal cord leptomeninges and white matter, which coincided with a mild gait disturbance in some surviving mice, and patchy demyelination was found in areas of inflammation. The acute gray matter pathology would appear to be the result of direct virus lytic effect. Although the late white matter lesion culminating in demyelination probably represents a cytocidal infection similar to the situation that exists in certain picornavirus carrier culture systems, a virus-induced immunopathological process merits further study.", "contents": "Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination. An unusual biphasic central nervous system disease developed in 3-week-old Swiss outbred mice after intracerebral inoculation of the DA strain of Theiler's murine encephalomyelitis virus. Nine to 20 days postinfection 86% of mice became paralyzed, and approximately one-half of these animals survived. During this period neuronal necrosis and microglial proliferation were seen in thalamus, brainstem, and spinal cord. There was an initial phase of virus growth in spinal cord followed by persistent infection at a lower concentration. Virus antigen was readily found in the cytoplasm of neurons by immunofluorescent staining early in the course of infection, whereas after 30 days there was a paucity of cells containing virus antigen which were present only in the spinal cord white matter. Between 1 and 5 months, an intense mononuclear inflammatory cell lesion evolved in the spinal cord leptomeninges and white matter, which coincided with a mild gait disturbance in some surviving mice, and patchy demyelination was found in areas of inflammation. The acute gray matter pathology would appear to be the result of direct virus lytic effect. Although the late white matter lesion culminating in demyelination probably represents a cytocidal infection similar to the situation that exists in certain picornavirus carrier culture systems, a virus-induced immunopathological process merits further study."} {"id": "PMID:164413", "title": "In ovo assay for Marek's disease virus and turkey herpesvirus.", "content": "Marek's disease virus (MDV) and the turkey herpesvirus (HVT) may be assayed on the chorioallantoic membrane (CAM) of the chicken embryo after intravenous inoculation of chicken embryo fibroblasts (CEF) or chicken blood leukocytes infected with these viruses. Free HVT, MDV associated with Marek's tumor cells, and lymphoblastoid cell lines derived from Marek's tumors, may be assayed in the same way. The intravenous assay is quicker than the yolk sac assay and somewhat more sensitive than in vitro or conventional CAM assay after direct inoculation of the CAM. The optimal time for inoculation was day 10 of embryo incubation; therafter the log-10 CAM lesions decreased as a negative linear function of embryo age at the time of inoculation. The log-10 CAM lesions increased as a positive linear function of the time since inoculation. The optimal time for counts was day 5 after inoculation. The log-10 CAM lesions was a linear function of the log-10 cells in the inoculum; the slope was 1.0. Venous in ovo inoculation caused as increase in the weight of the spleen proportional to the number of CAM lesions. Repression of the splenomegaly, by prior X irradiation of the embryo, did not reduce the number of CAM lesions. Embryols from lines inbred for susceptibility to Marek's disease produced more CAM lesions than embryos from resistant lines. This difference did not depend on prior exposure of the mothers to MDV or HVT.", "contents": "In ovo assay for Marek's disease virus and turkey herpesvirus. Marek's disease virus (MDV) and the turkey herpesvirus (HVT) may be assayed on the chorioallantoic membrane (CAM) of the chicken embryo after intravenous inoculation of chicken embryo fibroblasts (CEF) or chicken blood leukocytes infected with these viruses. Free HVT, MDV associated with Marek's tumor cells, and lymphoblastoid cell lines derived from Marek's tumors, may be assayed in the same way. The intravenous assay is quicker than the yolk sac assay and somewhat more sensitive than in vitro or conventional CAM assay after direct inoculation of the CAM. The optimal time for inoculation was day 10 of embryo incubation; therafter the log-10 CAM lesions decreased as a negative linear function of embryo age at the time of inoculation. The log-10 CAM lesions increased as a positive linear function of the time since inoculation. The optimal time for counts was day 5 after inoculation. The log-10 CAM lesions was a linear function of the log-10 cells in the inoculum; the slope was 1.0. Venous in ovo inoculation caused as increase in the weight of the spleen proportional to the number of CAM lesions. Repression of the splenomegaly, by prior X irradiation of the embryo, did not reduce the number of CAM lesions. Embryols from lines inbred for susceptibility to Marek's disease produced more CAM lesions than embryos from resistant lines. This difference did not depend on prior exposure of the mothers to MDV or HVT."} {"id": "PMID:164414", "title": "Mechanism of induction of cell-mediated immunity to virus infections: in vitro inhibition of intracellular multiplication of mouse adenovirus by immune spleen cells.", "content": "Mice were protected from lethal infection with mouse adenovirus (M-Ad) by adoptive transfer of immune spleen cells (ISC) that were prepared from mice immunized with M-Ad and not protected by sonicated ISC. However, a similar extent of protection was also observed by passive immunization with anti-M-Ad serum. In contrast, by in vitro experiments ISC were shown to be able to interrupt intracellular multiplication of M-Ad, whereas sonicated ISC, unimmunized mouse spleen cells, or anti-M-Ad serum were unable to do so. ISC were inhibitory in vitro when added within 12 h postinfection but not when added later. The inhibitory activity of ISC was regarded as due to cell killing by ISC, since the trypan blue exclusion test showed that above 80% of infected cells were killed by ISC even when 5'-fluorodeoxyuridine was added to the cells to block viral deoxyribonucleic acid synthesis, under which conditions control infected cells, to which ISC were not added or normal spleen cells were added, were kept alive at least for a few days. Kinetics studies in M-Ad-infected mice showed that the inhibitory activity of ISC became highest at 1 to 2 weeks postinfection and faded away thereafter in a few weeks, whereas serum antibody titer assayed by passive hemagglutination reached its peak level at about 4 weeks postinfection and declined gradually therafter.", "contents": "Mechanism of induction of cell-mediated immunity to virus infections: in vitro inhibition of intracellular multiplication of mouse adenovirus by immune spleen cells. Mice were protected from lethal infection with mouse adenovirus (M-Ad) by adoptive transfer of immune spleen cells (ISC) that were prepared from mice immunized with M-Ad and not protected by sonicated ISC. However, a similar extent of protection was also observed by passive immunization with anti-M-Ad serum. In contrast, by in vitro experiments ISC were shown to be able to interrupt intracellular multiplication of M-Ad, whereas sonicated ISC, unimmunized mouse spleen cells, or anti-M-Ad serum were unable to do so. ISC were inhibitory in vitro when added within 12 h postinfection but not when added later. The inhibitory activity of ISC was regarded as due to cell killing by ISC, since the trypan blue exclusion test showed that above 80% of infected cells were killed by ISC even when 5'-fluorodeoxyuridine was added to the cells to block viral deoxyribonucleic acid synthesis, under which conditions control infected cells, to which ISC were not added or normal spleen cells were added, were kept alive at least for a few days. Kinetics studies in M-Ad-infected mice showed that the inhibitory activity of ISC became highest at 1 to 2 weeks postinfection and faded away thereafter in a few weeks, whereas serum antibody titer assayed by passive hemagglutination reached its peak level at about 4 weeks postinfection and declined gradually therafter."} {"id": "PMID:164415", "title": "Effect of silica on virus infections in mice and mouse tissue culture.", "content": "Silica injections of mice have been reported to kill macrophages, thus allowing herpes simplex virus (HSV) to spread rapidly and leading to an increased severity of HSV infection. Thus, silica presumably could be used to eliminate lactic dehydrogenase virus (LDV) (a model for slow viruses), which is known to multiply exclusively in macrophages. Contrary to expectation, it was found that the LDV titers were increased in silica-injected mice as compared to the titers in control mice. Counts of peritoneal cells at different periods after silica injection showed that silica-induced macrophage damage in vivo resulted in proliferation and migration of macrophages, thus providing additional target cells for LDV replication and leading to high LDV titers. In vitro, silica ingestion also damaged the macrophages, but since no replacement of cells could occur by infiltration, decreased LDV titers were found. Similar findings were obtained with HSV. It is suggested that all persistent viruses multiplying in macrophages will show a similar recrudescence under comparable conditions.", "contents": "Effect of silica on virus infections in mice and mouse tissue culture. Silica injections of mice have been reported to kill macrophages, thus allowing herpes simplex virus (HSV) to spread rapidly and leading to an increased severity of HSV infection. Thus, silica presumably could be used to eliminate lactic dehydrogenase virus (LDV) (a model for slow viruses), which is known to multiply exclusively in macrophages. Contrary to expectation, it was found that the LDV titers were increased in silica-injected mice as compared to the titers in control mice. Counts of peritoneal cells at different periods after silica injection showed that silica-induced macrophage damage in vivo resulted in proliferation and migration of macrophages, thus providing additional target cells for LDV replication and leading to high LDV titers. In vitro, silica ingestion also damaged the macrophages, but since no replacement of cells could occur by infiltration, decreased LDV titers were found. Similar findings were obtained with HSV. It is suggested that all persistent viruses multiplying in macrophages will show a similar recrudescence under comparable conditions."} {"id": "PMID:164416", "title": "Detection of cellular hypersensitivity among multiple sclerosis (MS) patients to 6/94 virus; a parainfluenza type 1 isolate from MS brain tissue.", "content": "Multiple sclerosis (MS) patients and normal subjects were tested for cellular hypersensitivity, using the leukocyte migration inhibition test LMI), to a parainfluenza-1-virus (6/94), previously isolated from brain biopsy tissue of an MS patient. The response of MS patients as a group was not greater than that of normals to 6/94, but a significant increase in the response was observed among selected patients in the early active and chronic advanced stages of the disease. MS patients, however, did not differ from normal subjects in their cell response to Sendai virus, a similar parainfluenza type 1 virion used for comparison.", "contents": "Detection of cellular hypersensitivity among multiple sclerosis (MS) patients to 6/94 virus; a parainfluenza type 1 isolate from MS brain tissue. Multiple sclerosis (MS) patients and normal subjects were tested for cellular hypersensitivity, using the leukocyte migration inhibition test LMI), to a parainfluenza-1-virus (6/94), previously isolated from brain biopsy tissue of an MS patient. The response of MS patients as a group was not greater than that of normals to 6/94, but a significant increase in the response was observed among selected patients in the early active and chronic advanced stages of the disease. MS patients, however, did not differ from normal subjects in their cell response to Sendai virus, a similar parainfluenza type 1 virion used for comparison."} {"id": "PMID:164417", "title": "Isolation and characterization of the cyanogen bromide fragments of lobster arginine kinase (homarus vulgaris).", "content": "Arginine kinase was aminoethylated in order to block the five free thiol groups on the native enzyme, and then submitted to BrCN cleavage. The BrCN resulting peptides were soluble in propionic acid (10 percent) and subsequently submitted to gel-filtration. The large polypeptide subfractions were citraconylated and resubmitted to differnt gelchromatographies, whereas the short peptide subfractions were submitted to preparative paper electrochromatographies. Eight peptides of 2, 11, 17, 25, 61, 82, 86 and 132 amino acid residues were isolated, one of which is the overlapping of two peptides. The amino acid composition and the end group of all the isolated peptides were established. The short peptides (2, 11 and 17 residues) were sequenced. All peptides possess homoserine at C-terminal position because one methionyl residue is situated at the C-terminal position in the native protein. The polypeptide with 132 residues possessed N-acetylated residue at N-terminal position: therefore this polypeptide is located at the N-terminal position in the protein. The sum and account of each amino acid of the seven isolated peptides were compared to those of the intact protein: the sum of the seven peptides is 331 amino acid residues, whereas the whole protein contains 342 residues. The molecular weight of arginine kinase is revised and calculated on the basis of the present results (37, 687).", "contents": "Isolation and characterization of the cyanogen bromide fragments of lobster arginine kinase (homarus vulgaris). Arginine kinase was aminoethylated in order to block the five free thiol groups on the native enzyme, and then submitted to BrCN cleavage. The BrCN resulting peptides were soluble in propionic acid (10 percent) and subsequently submitted to gel-filtration. The large polypeptide subfractions were citraconylated and resubmitted to differnt gelchromatographies, whereas the short peptide subfractions were submitted to preparative paper electrochromatographies. Eight peptides of 2, 11, 17, 25, 61, 82, 86 and 132 amino acid residues were isolated, one of which is the overlapping of two peptides. The amino acid composition and the end group of all the isolated peptides were established. The short peptides (2, 11 and 17 residues) were sequenced. All peptides possess homoserine at C-terminal position because one methionyl residue is situated at the C-terminal position in the native protein. The polypeptide with 132 residues possessed N-acetylated residue at N-terminal position: therefore this polypeptide is located at the N-terminal position in the protein. The sum and account of each amino acid of the seven isolated peptides were compared to those of the intact protein: the sum of the seven peptides is 331 amino acid residues, whereas the whole protein contains 342 residues. The molecular weight of arginine kinase is revised and calculated on the basis of the present results (37, 687)."} {"id": "PMID:164431", "title": "Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis.", "content": "From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil.", "contents": "Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis. From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil."} {"id": "PMID:164432", "title": "Kynureninase-Type enzymes of Penicillum roqueforti, Aspergillus niger, Rhizopus stolonifer, and Pseudomonas fluorescens: further evidence for distinct kynureninase and hydroxykynureninase activities.", "content": "The kynureninase-type enzymes of three fungi and one bacterium were isolated and examined kinetically for their ability to catalyze the hydrolysis of L-kynurenine and L-3-hydroxykynurenine. The phycomycete Rhizopus stolonifer was found to contain a single, constitutive enzyme with Km for L-3-hydroxykynurenine and L-kynurenine of 6.67 times 10-minus 6 and 2.5 times 10-minus 4 M, respectively. The ascomycetes Aspergillus niger and Penicillium roqueforti each contain an enzyme, induced by L-tryptophan, with similar Km for L-3-hydroxykynurenine and L-kynurenine ranging from 5.9 times 10-minus 5 to 14.3 times 10-minus 5 M, as well as a constitutive enzyme with Km for the two substrates of similar to 4 times 10-minus 6 M and 10-minus 4 M. The bacterium Pseudomonas fluorescens has a single, inducible enzyme with Km for L-3-hydroxykynurenine and L-kynurenine of 5 times 10-minus 4 and 7 times 10-minus 5 M. In addition, significant differences in maximal velocities (Vmax) were observed in two cases. The Vmax of the inducible activity from P. fluorescens was 4.5 times greater for L-kynurenine than L-3-hydroxykynurenine, whereas the Vmax of the constitutive activity from R. stolonifer was 2.5 times greater for L-3-hydroxykynurenine. It is concluded (i) that the constitutive activities are hydroxykynureninases involved in the biosynthesis of nicotinamide adenine dinucleotide from L-tryptophan, (ii) that the inducible activities are kynureninases involved in the catabolism of L-tryptophan to anthranilate, and (iii) that R. stolonifer and P. fluorescens, respectively, carry the most specific examples of each type of enzyme.", "contents": "Kynureninase-Type enzymes of Penicillum roqueforti, Aspergillus niger, Rhizopus stolonifer, and Pseudomonas fluorescens: further evidence for distinct kynureninase and hydroxykynureninase activities. The kynureninase-type enzymes of three fungi and one bacterium were isolated and examined kinetically for their ability to catalyze the hydrolysis of L-kynurenine and L-3-hydroxykynurenine. The phycomycete Rhizopus stolonifer was found to contain a single, constitutive enzyme with Km for L-3-hydroxykynurenine and L-kynurenine of 6.67 times 10-minus 6 and 2.5 times 10-minus 4 M, respectively. The ascomycetes Aspergillus niger and Penicillium roqueforti each contain an enzyme, induced by L-tryptophan, with similar Km for L-3-hydroxykynurenine and L-kynurenine ranging from 5.9 times 10-minus 5 to 14.3 times 10-minus 5 M, as well as a constitutive enzyme with Km for the two substrates of similar to 4 times 10-minus 6 M and 10-minus 4 M. The bacterium Pseudomonas fluorescens has a single, inducible enzyme with Km for L-3-hydroxykynurenine and L-kynurenine of 5 times 10-minus 4 and 7 times 10-minus 5 M. In addition, significant differences in maximal velocities (Vmax) were observed in two cases. The Vmax of the inducible activity from P. fluorescens was 4.5 times greater for L-kynurenine than L-3-hydroxykynurenine, whereas the Vmax of the constitutive activity from R. stolonifer was 2.5 times greater for L-3-hydroxykynurenine. It is concluded (i) that the constitutive activities are hydroxykynureninases involved in the biosynthesis of nicotinamide adenine dinucleotide from L-tryptophan, (ii) that the inducible activities are kynureninases involved in the catabolism of L-tryptophan to anthranilate, and (iii) that R. stolonifer and P. fluorescens, respectively, carry the most specific examples of each type of enzyme."} {"id": "PMID:164433", "title": "Amino acid transport in membrane vesicles of obligately anaerobic Veillonella alcalescens.", "content": "Membrane vesicles of Veillonella alcalescens, grown in the presence of L-lactate and KNO-3, actively transport amino acids under anaerobic conditions in the presence of several electron donors and the electron acceptor nitrate. The highest initial rates of uptake are obtained with L-lactate, followed by reduced nicotinamide adenine dinucleotide, glycerol-1-phosphate, formate, and L-malate.. The membrane vesicles contain the dehydrogenases for these electron donors, and these enzymes are coupled with nitrate reductase. In membrane vesicles from cells, grown in the presence of nitrate, the dehydrogenases are not coupled with fumarate reducatase, and anaerobic transport of amino acids does not occur with fumarate as electron acceptor. Under aerobic conditions none of the physiological electron donors can energize transport. However, a high rate of uptake is observed with the electron donor system ascorbate-phenazine metho-sulfate. This electron donor system also effectively energizes transport under anaerobicconditions in the presence of the electron acceptor nitrate.", "contents": "Amino acid transport in membrane vesicles of obligately anaerobic Veillonella alcalescens. Membrane vesicles of Veillonella alcalescens, grown in the presence of L-lactate and KNO-3, actively transport amino acids under anaerobic conditions in the presence of several electron donors and the electron acceptor nitrate. The highest initial rates of uptake are obtained with L-lactate, followed by reduced nicotinamide adenine dinucleotide, glycerol-1-phosphate, formate, and L-malate.. The membrane vesicles contain the dehydrogenases for these electron donors, and these enzymes are coupled with nitrate reductase. In membrane vesicles from cells, grown in the presence of nitrate, the dehydrogenases are not coupled with fumarate reducatase, and anaerobic transport of amino acids does not occur with fumarate as electron acceptor. Under aerobic conditions none of the physiological electron donors can energize transport. However, a high rate of uptake is observed with the electron donor system ascorbate-phenazine metho-sulfate. This electron donor system also effectively energizes transport under anaerobicconditions in the presence of the electron acceptor nitrate."} {"id": "PMID:164434", "title": "Intergration of the receptor for bacteriophage lambda in the outer membrane of Escherichia coli: coupling with cell division.", "content": "Induction of the synthesis of the receptor for phage lambda is obtained by adding maltose and adenosine 3'-5'-cyclic monophosphate to glucose grown cells of Escherichia coli. Bacteria induced for a short period of time were infected with a high multiplicity of phage lambda , and examined under the electron microscope. Only a fraction of the bacteria were seen to have adsorbed a large number of phage particles. The majority of such bacteria had a constriction indicating formation of a septum, and, in this case, the density of adsorbed particles was highest in the vicinity of the constriction. When found on bacteria showing no sign of septum formation, the adsorbed particles were asymmetrically distributed, one pole of the bacteria being more heavily covered with phage particles than the other. Such asymetrically covered bacteria are believed to have originated from cells which divided during the induction period. The results suggest that the receptor for phage lambda, a protein of the outer membrane, is integrated in the cell envelope during the last quarter of each generation and that the integration process is initiated in the vicinity of the forming septum.", "contents": "Intergration of the receptor for bacteriophage lambda in the outer membrane of Escherichia coli: coupling with cell division. Induction of the synthesis of the receptor for phage lambda is obtained by adding maltose and adenosine 3'-5'-cyclic monophosphate to glucose grown cells of Escherichia coli. Bacteria induced for a short period of time were infected with a high multiplicity of phage lambda , and examined under the electron microscope. Only a fraction of the bacteria were seen to have adsorbed a large number of phage particles. The majority of such bacteria had a constriction indicating formation of a septum, and, in this case, the density of adsorbed particles was highest in the vicinity of the constriction. When found on bacteria showing no sign of septum formation, the adsorbed particles were asymmetrically distributed, one pole of the bacteria being more heavily covered with phage particles than the other. Such asymetrically covered bacteria are believed to have originated from cells which divided during the induction period. The results suggest that the receptor for phage lambda, a protein of the outer membrane, is integrated in the cell envelope during the last quarter of each generation and that the integration process is initiated in the vicinity of the forming septum."} {"id": "PMID:164435", "title": "Deletion of the Escherichia coli crp gene.", "content": "Spontaneous crp mutants Escherichia coli were selected from a strain that does not require 3',5'-cyclic adenosine monophosphate for CAP activity. Several deletions of the crp gene were characterized. The crp gene was not essential for growth of E. coli. crp mutations reduced the donor ability of Hfr strains.", "contents": "Deletion of the Escherichia coli crp gene. Spontaneous crp mutants Escherichia coli were selected from a strain that does not require 3',5'-cyclic adenosine monophosphate for CAP activity. Several deletions of the crp gene were characterized. The crp gene was not essential for growth of E. coli. crp mutations reduced the donor ability of Hfr strains."} {"id": "PMID:164436", "title": "Demonstation that thymine dimers are excised as oligonucleotides from specifically incised ultraviolet-irradiated deoxyribonucleic acid.", "content": "The average size of the dimer-containing acid-soluble oligonucleotides after incubation of specifically incised DNA with two dimer excising nuclease activities has been determined to be about 8 nucleotides.", "contents": "Demonstation that thymine dimers are excised as oligonucleotides from specifically incised ultraviolet-irradiated deoxyribonucleic acid. The average size of the dimer-containing acid-soluble oligonucleotides after incubation of specifically incised DNA with two dimer excising nuclease activities has been determined to be about 8 nucleotides."} {"id": "PMID:164437", "title": "Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells.", "content": "In fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects.", "contents": "Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells. In fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects."} {"id": "PMID:164438", "title": "Possible role of adenosine cyclic 3':5'-monophosphate phosphodiesterase in the morphological transformation of Chinese hamster ovary cells mediated by N6,O2-dibutyryl adenosine cyclic 3':5\"-monophosphate.", "content": "We have demonstrated that in Chinese hamster ovary (CHO) cells, N6,O2'-dibutyryl adenosine cyclic 3':5'-monophosphate (dibutyryl cyclic AMP) has a remarkable morphogenetic effect in converting cells of a compact, epithelial-like morphology into a spindle-shaped, fibroblast-like form. Homogenates of CHO cells were found to contain two adenosine cyclic 3':5'-monophosphate (cyclic AMP) phosphodiesterase (EC 3.1.4.c) activities, which differ in apparent Km with respect to their substrate, cyclic AMP. These were designated cyclic AMP phosphodiesterase I, with a low Km of 2 to 5 muM and cyclic AMP phosphodiesterase II, with a high Km of 1 to 3 mM. Cyclic AMP phosphodiesterase I was competitively inhibited by N6-monobutyryl and dibutyryl cyclic AMP, with apparent Ki values of 40 to 60 muM and 0.25 to 0.35 mM, respectively. Experimental evidence demonstrates that the effect of exogenous dibutyryl cyclic AMP on cell morphology is a result of an increase in the endogenous level of cyclic AMP. This increase appears to be due largely to the inhibitory action of intracellular N6-monobutyryl cyclic AMP on cyclic AMP phosphodiesterase I, which results in a decreased rate of degradation of intracellular cyclic AMP.", "contents": "Possible role of adenosine cyclic 3':5'-monophosphate phosphodiesterase in the morphological transformation of Chinese hamster ovary cells mediated by N6,O2-dibutyryl adenosine cyclic 3':5\"-monophosphate. We have demonstrated that in Chinese hamster ovary (CHO) cells, N6,O2'-dibutyryl adenosine cyclic 3':5'-monophosphate (dibutyryl cyclic AMP) has a remarkable morphogenetic effect in converting cells of a compact, epithelial-like morphology into a spindle-shaped, fibroblast-like form. Homogenates of CHO cells were found to contain two adenosine cyclic 3':5'-monophosphate (cyclic AMP) phosphodiesterase (EC 3.1.4.c) activities, which differ in apparent Km with respect to their substrate, cyclic AMP. These were designated cyclic AMP phosphodiesterase I, with a low Km of 2 to 5 muM and cyclic AMP phosphodiesterase II, with a high Km of 1 to 3 mM. Cyclic AMP phosphodiesterase I was competitively inhibited by N6-monobutyryl and dibutyryl cyclic AMP, with apparent Ki values of 40 to 60 muM and 0.25 to 0.35 mM, respectively. Experimental evidence demonstrates that the effect of exogenous dibutyryl cyclic AMP on cell morphology is a result of an increase in the endogenous level of cyclic AMP. This increase appears to be due largely to the inhibitory action of intracellular N6-monobutyryl cyclic AMP on cyclic AMP phosphodiesterase I, which results in a decreased rate of degradation of intracellular cyclic AMP."} {"id": "PMID:164440", "title": "Surface carbohydrates of hamster fibroblasts. I. Chemical characterization of surface-labeled glycosphingolipids and aspecific ceramide tetrasaccharide for transformants.", "content": "1. Neutral glycosphingolipids of hamster fibroblast NIL cells have been characterized as follows: glucosylceramide, lactosylceramide (betaGall yields 4Glc yields Cer), a digalactosylceramide (alphaGall yields 4betaGal yields Cer), a trihexosylceramide (alphaGall yields 4betaGall yields 4Glc yields Cer), two kinds of ceramide tetrasaccharides (A: alphaGa1NAcl yields 3betaGalNAcl yields 3alphaGall yields 4betaGall yields 1Cer, a new type of Forssman active glycolipid; B: globoside, betaGalNAcl yields 3alphaGall yields 4betaGall yields 4betaGlc yields Cer), and a ceramide pentasaccharide having a classical structure for Forssman antigen (alphaGalNAcl yields 3betaGalNAcl yields 3alphaGall yields 4betaGall yields 4Glc yields Cer). 2. Neutral glycosphingolipids of polyoma virus-transformed NIL cells (NILpy) have been characterized as having an additional ceramide tetrasaccharide which was absent in normal NIL cells. The structure of this specific glycolipid was identified as lacto-N-neotetraosylceramide (betaGall yields 4betaGlc-NAcl yields 3betaGall yields 4Glc yields Cer). Chemical quantities of ceramide tetra- and pentasaccharides in NILpy cells were much lower than in NIL cells. 3. All of these glycolipids, except glucosylceramide and lactosylceramide, were labeled externally by galactose oxidase and tritiated borohydride according to the method previously described (GAHMBERG, C. G, and HAKOMORI, S. (1973) J. Biol. Chem. 248, 4311-4317). The specific activities of the label in glycolipid of NIHpy cells were much greater than that in NIL cells, i.e. reactivity of glycolipids with galactose oxidase in NIHpy cells was much higher than for NIL cells. The surface label in glycolipids was cell cycle-dependent in NIL cells, and a remarkable exposure of a galactosyl residue of a ceramide tetrasaccharide was demonstrated only on the surface of NILpy cells, due to the presence of lacto-N-neotetraosylceramide.", "contents": "Surface carbohydrates of hamster fibroblasts. I. Chemical characterization of surface-labeled glycosphingolipids and aspecific ceramide tetrasaccharide for transformants. 1. Neutral glycosphingolipids of hamster fibroblast NIL cells have been characterized as follows: glucosylceramide, lactosylceramide (betaGall yields 4Glc yields Cer), a digalactosylceramide (alphaGall yields 4betaGal yields Cer), a trihexosylceramide (alphaGall yields 4betaGall yields 4Glc yields Cer), two kinds of ceramide tetrasaccharides (A: alphaGa1NAcl yields 3betaGalNAcl yields 3alphaGall yields 4betaGall yields 1Cer, a new type of Forssman active glycolipid; B: globoside, betaGalNAcl yields 3alphaGall yields 4betaGall yields 4betaGlc yields Cer), and a ceramide pentasaccharide having a classical structure for Forssman antigen (alphaGalNAcl yields 3betaGalNAcl yields 3alphaGall yields 4betaGall yields 4Glc yields Cer). 2. Neutral glycosphingolipids of polyoma virus-transformed NIL cells (NILpy) have been characterized as having an additional ceramide tetrasaccharide which was absent in normal NIL cells. The structure of this specific glycolipid was identified as lacto-N-neotetraosylceramide (betaGall yields 4betaGlc-NAcl yields 3betaGall yields 4Glc yields Cer). Chemical quantities of ceramide tetra- and pentasaccharides in NILpy cells were much lower than in NIL cells. 3. All of these glycolipids, except glucosylceramide and lactosylceramide, were labeled externally by galactose oxidase and tritiated borohydride according to the method previously described (GAHMBERG, C. G, and HAKOMORI, S. (1973) J. Biol. Chem. 248, 4311-4317). The specific activities of the label in glycolipid of NIHpy cells were much greater than that in NIL cells, i.e. reactivity of glycolipids with galactose oxidase in NIHpy cells was much higher than for NIL cells. The surface label in glycolipids was cell cycle-dependent in NIL cells, and a remarkable exposure of a galactosyl residue of a ceramide tetrasaccharide was demonstrated only on the surface of NILpy cells, due to the presence of lacto-N-neotetraosylceramide."} {"id": "PMID:164441", "title": "Cyclic nucleotide phosphodiesterases and thyroid hormones.", "content": "Evidence is presented that modulation of the maximum velocity of a particulate low K-m cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase by thyroid hormones is one mechanism for the regulation of the responsiveness of rat epididymal adipocytes to lipolytic agents such as epinephrine and glucagon. Fat cells of propylthiouracil-induced hypothyroid rats are unresponsive to lipolytic agents and the V-max of particulate low K-m cyclic AMP phosphodiesterase of these cells is elevated above normal. In vivo treatment of hypothyroid rats with triiodothyronine restores to control values both the lipolytic response of the fat cells to epinephrine and the V-max of the particulate bound low K-m cyclic AMP phosphodiesterase. No similar correlation is found with the soluble high K-m cyclic AMP phosphodiesterase. The phosphodiesterases of fat cells from normal and hypothyroid rats respond identically in vitro to propylthiouracil, triiodothyronine, methylisobutylxanthine, or theophylline, although the particulate low K-m cyclic AMP phosphodiesterase is inhibited to a greater extent than soluble cyclic guanosine 3':5'-monophosphate phosphodiesterase activity. Protein kinase of fat cells from hypothyroid rats can be stimulated by cyclic AMP to the same total activity as observed in fat cells of normal rats. However, less of the protein kinase in fat cells from hypothyroid rats was in the cyclic AMP-independent form. This shift in the equilibrium of protein kinase forms is consistent with an increased activity of low K-m cyclic AMP phosphodiesterase and probably results from a lowering of the lipolytically significant pool of cyclic AMP.", "contents": "Cyclic nucleotide phosphodiesterases and thyroid hormones. Evidence is presented that modulation of the maximum velocity of a particulate low K-m cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase by thyroid hormones is one mechanism for the regulation of the responsiveness of rat epididymal adipocytes to lipolytic agents such as epinephrine and glucagon. Fat cells of propylthiouracil-induced hypothyroid rats are unresponsive to lipolytic agents and the V-max of particulate low K-m cyclic AMP phosphodiesterase of these cells is elevated above normal. In vivo treatment of hypothyroid rats with triiodothyronine restores to control values both the lipolytic response of the fat cells to epinephrine and the V-max of the particulate bound low K-m cyclic AMP phosphodiesterase. No similar correlation is found with the soluble high K-m cyclic AMP phosphodiesterase. The phosphodiesterases of fat cells from normal and hypothyroid rats respond identically in vitro to propylthiouracil, triiodothyronine, methylisobutylxanthine, or theophylline, although the particulate low K-m cyclic AMP phosphodiesterase is inhibited to a greater extent than soluble cyclic guanosine 3':5'-monophosphate phosphodiesterase activity. Protein kinase of fat cells from hypothyroid rats can be stimulated by cyclic AMP to the same total activity as observed in fat cells of normal rats. However, less of the protein kinase in fat cells from hypothyroid rats was in the cyclic AMP-independent form. This shift in the equilibrium of protein kinase forms is consistent with an increased activity of low K-m cyclic AMP phosphodiesterase and probably results from a lowering of the lipolytically significant pool of cyclic AMP."} {"id": "PMID:164442", "title": "Sequence position of 3-hydroxyproline in basement membrane collagen. Isolation of glycyl-3-hydroxyprolyl-4-hydroxyproline from swine kidney.", "content": "The position of 3-hydroxyproline was investigated in the triplet sequences of peptides released by collagenase digestion of a collagen preparation from kidney cortex. Composition of the collagen preparation indicated that it was largely or wholly of basement membrane origin. 3-Hydroxyproline was detected in only one sequence, the tripeptide, glycyl-3-hydroxyprolyl-4-hydroxyproline, which accounted for a major fraction of the total 3-hydroxyproline obtained in the peptides released by collagenase. Preliminary data, based on sequencing the peptide mixture released by collagenase treatment, suggested that, in contrast, 4-hydroxyproline occurs predominantly if not exclusively in the Y position of Gly-X-Y triplet sequences in the collagen preparation studied.", "contents": "Sequence position of 3-hydroxyproline in basement membrane collagen. Isolation of glycyl-3-hydroxyprolyl-4-hydroxyproline from swine kidney. The position of 3-hydroxyproline was investigated in the triplet sequences of peptides released by collagenase digestion of a collagen preparation from kidney cortex. Composition of the collagen preparation indicated that it was largely or wholly of basement membrane origin. 3-Hydroxyproline was detected in only one sequence, the tripeptide, glycyl-3-hydroxyprolyl-4-hydroxyproline, which accounted for a major fraction of the total 3-hydroxyproline obtained in the peptides released by collagenase. Preliminary data, based on sequencing the peptide mixture released by collagenase treatment, suggested that, in contrast, 4-hydroxyproline occurs predominantly if not exclusively in the Y position of Gly-X-Y triplet sequences in the collagen preparation studied."} {"id": "PMID:164443", "title": "Maturation pathway for Novikoff ascites hepatoma 5.8 S ribosomal ribonucleic acid. Evidence for its presence in 32 S nuclear ribonucleic acid.", "content": "Evidence that 32 S nRNA contains 5.8 S rRNA was provided by studies on specific oligonucleotide sequences of these RNA species. Purified 32P-labeled 5.8 and 28 S rRNA and 32 S RNA were digested with T-1 ribonuclease, and the products were fractionated according to chain length by chromatography on DEAE-Sephadex A-25 at neutral pH. The oligonucleotides in Peak 8 were treated with alkaline phosphatase and the products were separated by two-dimensional electrophoresis on cellulose acetate at pH 3.5 and DEAE-paper in 7% formic acid. Seven unique oligonucleotide markers for 5.8 S rRNA including the methylated octanucleotide A-A-U-U-Gm-G-A-Gp were present in 32 S RNA but were not found in 28 S rRNA, indicating that 5.8 S rRNA is directly derived from the 32 S nucleolar precursor. These studies confirm a maturation pathway for rRNA species in which 32 S nucleolar RNA is a precursor of 5.8 S rRNA as well as 28 S rRNA.", "contents": "Maturation pathway for Novikoff ascites hepatoma 5.8 S ribosomal ribonucleic acid. Evidence for its presence in 32 S nuclear ribonucleic acid. Evidence that 32 S nRNA contains 5.8 S rRNA was provided by studies on specific oligonucleotide sequences of these RNA species. Purified 32P-labeled 5.8 and 28 S rRNA and 32 S RNA were digested with T-1 ribonuclease, and the products were fractionated according to chain length by chromatography on DEAE-Sephadex A-25 at neutral pH. The oligonucleotides in Peak 8 were treated with alkaline phosphatase and the products were separated by two-dimensional electrophoresis on cellulose acetate at pH 3.5 and DEAE-paper in 7% formic acid. Seven unique oligonucleotide markers for 5.8 S rRNA including the methylated octanucleotide A-A-U-U-Gm-G-A-Gp were present in 32 S RNA but were not found in 28 S rRNA, indicating that 5.8 S rRNA is directly derived from the 32 S nucleolar precursor. These studies confirm a maturation pathway for rRNA species in which 32 S nucleolar RNA is a precursor of 5.8 S rRNA as well as 28 S rRNA."} {"id": "PMID:164444", "title": "Bovine serum albumin. Study of the fatty acid and steroid binding sites using spin-labeled lipids.", "content": "Three spin-labeled derivatives of stearic acid and two derivatives of palmitic acid have been used to study the structure of the strong fatty acid binding site of bovine serum albumin. The steroid and indole binding sites have been studied using spin-labeled derivatives of androstol and indole, respectively. Paramagnetic resonance and fluorescence quenching data suggest that the fatty acid, steroid, and indole binding sites may be identical. The mobility of the nitroxyl group at C-8 of palmitic acid bound to albumin at a 1:1 molar ratio is unaffected when the carboxyl group is esterified. When the nitroxyl group is located at C-5 on this acid its motion is detectably increased by esterification of the carboxyl group but the magnitude of this change is small. This result suggests that the carboxyl group may play a minor role in the binding of fatty acids to the strongest fatty acid binding site of albumin. When stearic acid derivatives bearing the nitroxide at C-5, C-12, and C-16 are bound to albumin at a ligand to albumin ratio of 1, the order of mobility at 0-30 degrees is C-16 greater than C-12 congruent to C-5. Although motion at the methyl terminus is always greater than at the COOH terminus in the range 0-60 degrees, a simple monotonic increase in chain motion between the two termini is not observed. Arrhenius plots of the motion parameters for these bound fatty acids show two abrupt changes in slope. The temperature ranges for these changes are 15-23 degrees and 38-45 degrees. These results suggest that when one mole of spin-labeled fatty acid is bound to albumin, the protein undergoes a conformational change in each of these temperature ranges.", "contents": "Bovine serum albumin. Study of the fatty acid and steroid binding sites using spin-labeled lipids. Three spin-labeled derivatives of stearic acid and two derivatives of palmitic acid have been used to study the structure of the strong fatty acid binding site of bovine serum albumin. The steroid and indole binding sites have been studied using spin-labeled derivatives of androstol and indole, respectively. Paramagnetic resonance and fluorescence quenching data suggest that the fatty acid, steroid, and indole binding sites may be identical. The mobility of the nitroxyl group at C-8 of palmitic acid bound to albumin at a 1:1 molar ratio is unaffected when the carboxyl group is esterified. When the nitroxyl group is located at C-5 on this acid its motion is detectably increased by esterification of the carboxyl group but the magnitude of this change is small. This result suggests that the carboxyl group may play a minor role in the binding of fatty acids to the strongest fatty acid binding site of albumin. When stearic acid derivatives bearing the nitroxide at C-5, C-12, and C-16 are bound to albumin at a ligand to albumin ratio of 1, the order of mobility at 0-30 degrees is C-16 greater than C-12 congruent to C-5. Although motion at the methyl terminus is always greater than at the COOH terminus in the range 0-60 degrees, a simple monotonic increase in chain motion between the two termini is not observed. Arrhenius plots of the motion parameters for these bound fatty acids show two abrupt changes in slope. The temperature ranges for these changes are 15-23 degrees and 38-45 degrees. These results suggest that when one mole of spin-labeled fatty acid is bound to albumin, the protein undergoes a conformational change in each of these temperature ranges."} {"id": "PMID:164445", "title": "Exploitation of hormone-induced conformational changes to label selectively a component of rat liver plasma membranes.", "content": "The kinetics for inactivation of rat liver plasma membrane adenylate cyclase by iodoacetic acid and iodoacetamide has been measured in the presence and absence of glucagon. Glucagon stimulated the rate of iodoacetic acid inhibition by a factor 9f 2.3-fold and iodoacetamide inhibition by 10-fold. These results suggest that interaction of glucagon with its receptor in the membrane resulted in conformational changes which increased either the exposure or nucleophilicity of one or more sulfhydryl groups crucial for adenylate cyclase activity. Membranes were treated with radioactively labeled iodoacetamide or iodoacetic acid in the presence or absence of glucagon and run on 5 and 7.5% sodium dodecylsulfate polyacrylamide gels. These labeling experiments revealed that two membrane components were more extensively labeled in the presence of glucagon. The first component had an apparent molecular weight of 240,000 on sodium dodecyl sulfate gels and stained positive with Coomassie blue and periodate Schiff reagent. This polypeptide accounted for approximately 1.3% of the total membrane protein. The second component had an apparent molecular weight less than 10,000 and could not be correlated directly with a well defined protein band on sodium dodecyl sulfate polyacrylamide gels. The enhancement in labeling of the 240,000 molecular weight component seen in the presence of glucagon agreed very well with that predicted from the kinetics for inhibition of adenylate cyclase activity in the presence and absence of glucagon. This correlation suggests that the component selectively labeled by this technique may be an integral component of the adenylate cyclase system and that hormone-induced conformational changes may be used to selectively label components of the adenylate cyclase system in mammalian membranes.", "contents": "Exploitation of hormone-induced conformational changes to label selectively a component of rat liver plasma membranes. The kinetics for inactivation of rat liver plasma membrane adenylate cyclase by iodoacetic acid and iodoacetamide has been measured in the presence and absence of glucagon. Glucagon stimulated the rate of iodoacetic acid inhibition by a factor 9f 2.3-fold and iodoacetamide inhibition by 10-fold. These results suggest that interaction of glucagon with its receptor in the membrane resulted in conformational changes which increased either the exposure or nucleophilicity of one or more sulfhydryl groups crucial for adenylate cyclase activity. Membranes were treated with radioactively labeled iodoacetamide or iodoacetic acid in the presence or absence of glucagon and run on 5 and 7.5% sodium dodecylsulfate polyacrylamide gels. These labeling experiments revealed that two membrane components were more extensively labeled in the presence of glucagon. The first component had an apparent molecular weight of 240,000 on sodium dodecyl sulfate gels and stained positive with Coomassie blue and periodate Schiff reagent. This polypeptide accounted for approximately 1.3% of the total membrane protein. The second component had an apparent molecular weight less than 10,000 and could not be correlated directly with a well defined protein band on sodium dodecyl sulfate polyacrylamide gels. The enhancement in labeling of the 240,000 molecular weight component seen in the presence of glucagon agreed very well with that predicted from the kinetics for inhibition of adenylate cyclase activity in the presence and absence of glucagon. This correlation suggests that the component selectively labeled by this technique may be an integral component of the adenylate cyclase system and that hormone-induced conformational changes may be used to selectively label components of the adenylate cyclase system in mammalian membranes."} {"id": "PMID:164446", "title": "Purification and properties of a soluble nicotinamide adenine dinucleotide-linked isocitrate dehydrogenase from Crithidia fasciculata.", "content": "A soluble NAD+-linked isocitrate dehydrogenase has been isolated from Crithidia fasciculata. The enzyme was purified 128-fold, almost to homogeneity, and was highly specific for NAD+ as the coenzyme. There is also a cytoplasmic NADP+-linked and a mitochondrial isocitrate dehydrogenase in the organism. Studies of the physical and kinetic properties of the soluble NAD+-isocitrate dehydrogenase from this organism showed that it resembled microbial NADP+-isocitrate dehydrogenases in general, all of which are cytoplasmic enzymes. The enzyme appeared not to be related to other NAD+-isocitrate dehydrogenases, which are found in the mitochondria of eukaryotic cells. The molecular weight of the soluble NAD+-isocitrate dehydrogenase was 105,000 which is within the range of the values for microbial NADP+-isocitrate dehydrogenases. Similar to the NADP+-isocitrate dehydrogenase in this organism, the enzyme was inhibited in a concerted manner by glyoxalate plus oxalacetate. Kinetic analysis revealed that Mn2+ was involved in the binding of isocitrate to the enzyme. Inhibition of the NAD+-linked isocitrate dehydrogenase by p-chloromercuribenzoate could be prevented by prior incubation of the enzyme with both Mn2+ and isocitrate; however, neither ion alone conferred protection. Free isocitrate, free Mn2+, and the Mn2+-isocitrate complex could all bind to the enzyme. Four different mechanisms with respect to the binding of isocitrate to the enzyme were tested. Of these, the formation of the active enzyme-Mn2+-isocitrate complex from (a) the random binding of Mn2+, isocitrate, and the Mn2+-isocitrate complex, or (b) the binding of Mn2+-isocitrate with free Mn2+ and isocitrate acting as dead-end competitors were both in agreement with these data.", "contents": "Purification and properties of a soluble nicotinamide adenine dinucleotide-linked isocitrate dehydrogenase from Crithidia fasciculata. A soluble NAD+-linked isocitrate dehydrogenase has been isolated from Crithidia fasciculata. The enzyme was purified 128-fold, almost to homogeneity, and was highly specific for NAD+ as the coenzyme. There is also a cytoplasmic NADP+-linked and a mitochondrial isocitrate dehydrogenase in the organism. Studies of the physical and kinetic properties of the soluble NAD+-isocitrate dehydrogenase from this organism showed that it resembled microbial NADP+-isocitrate dehydrogenases in general, all of which are cytoplasmic enzymes. The enzyme appeared not to be related to other NAD+-isocitrate dehydrogenases, which are found in the mitochondria of eukaryotic cells. The molecular weight of the soluble NAD+-isocitrate dehydrogenase was 105,000 which is within the range of the values for microbial NADP+-isocitrate dehydrogenases. Similar to the NADP+-isocitrate dehydrogenase in this organism, the enzyme was inhibited in a concerted manner by glyoxalate plus oxalacetate. Kinetic analysis revealed that Mn2+ was involved in the binding of isocitrate to the enzyme. Inhibition of the NAD+-linked isocitrate dehydrogenase by p-chloromercuribenzoate could be prevented by prior incubation of the enzyme with both Mn2+ and isocitrate; however, neither ion alone conferred protection. Free isocitrate, free Mn2+, and the Mn2+-isocitrate complex could all bind to the enzyme. Four different mechanisms with respect to the binding of isocitrate to the enzyme were tested. Of these, the formation of the active enzyme-Mn2+-isocitrate complex from (a) the random binding of Mn2+, isocitrate, and the Mn2+-isocitrate complex, or (b) the binding of Mn2+-isocitrate with free Mn2+ and isocitrate acting as dead-end competitors were both in agreement with these data."} {"id": "PMID:164447", "title": "The compatibility of netropsin and actinomycin binding to natural deoxyribonucleic acid.", "content": "The simultaneous binding of netropsin and actinomycin to four natural DNAs was studied to determine the influence of one ligand on the binding of the other. Actinomycin binds specifically to GC sites, whereas netropsin binds specifically to AT sites. Spectral titrations, thermal denaturation, and analytical buoyant density centrifugation were employed to measure the binding interference of these drugs. The binding of actinomycin to DNA was decreased by the presence of netropsin. Increasing the GC content of the DNA resulted in a decreased effect of netropsin on actinomycin binding. Quantitative analysis of the binding parameters indicated that netropsin and actinomycin can bind in close proximity along the DNA chain. Supercoiled DNA gave the same result as linear DNA. These results imply that DNA can absorb alterations in conformation within a short distance.", "contents": "The compatibility of netropsin and actinomycin binding to natural deoxyribonucleic acid. The simultaneous binding of netropsin and actinomycin to four natural DNAs was studied to determine the influence of one ligand on the binding of the other. Actinomycin binds specifically to GC sites, whereas netropsin binds specifically to AT sites. Spectral titrations, thermal denaturation, and analytical buoyant density centrifugation were employed to measure the binding interference of these drugs. The binding of actinomycin to DNA was decreased by the presence of netropsin. Increasing the GC content of the DNA resulted in a decreased effect of netropsin on actinomycin binding. Quantitative analysis of the binding parameters indicated that netropsin and actinomycin can bind in close proximity along the DNA chain. Supercoiled DNA gave the same result as linear DNA. These results imply that DNA can absorb alterations in conformation within a short distance."} {"id": "PMID:164448", "title": "Effect of Ricinus communis toxin on cyclic adenosine 3':5'-monophosphate metabolism in Yoshida ascites sarcoma cells.", "content": "Prostaglandin E1 (2.5 mug/ml) enhanced the level of cyclic adenosine 3':5'-monophosphate (cyclic AMP) three to four times in Yoshida ascites sarcoma (YS) cells cultured in vitro. When Ricinus communis toxin (RC-toxin) was added 30 min after the addition of prostaglandin E1, the enhanced level of cyclic AMP in the YS cells decreased rapidly. Of RC-toxin, 0.2 mug/ml was enough to produce the maximum effect. By addition of 5 mM lactose with RC-toxin, approximately 60% of the RC-toxin effect on the levels of cyclic AMP was abolished. This indicates that the specific binding of RC-toxin on the surface membrane is largely responsible for the observed decrease of the cyclic AMP level. The toxin treatment did not induce either leakage of cyclic AMP from the cell or change in the activity of cyclic AMP phosphodiesterase. However, the treatment of YS cells with RC-toxin caused a decrease of adenylate cyclase activity when the activity was measured at a substrate concentration of 0.15 mM ATP. In contrast, there was little difference with the control when the activity was assayed at a higher ATP concentration, 0.24 mM. It was found that the K-m of adenylate cyclase for ATP was changed by RC-toxin from 0.1 to 0.25 mM, and that the Mg2+ activation of the enzyme observable in untreated cells disappeared. These results suggested that the decrease in the level of cyclic AMP in YS cells induced by RC-toxin can be explained in terms of the change in K-m of the adenylate cyclase activity.", "contents": "Effect of Ricinus communis toxin on cyclic adenosine 3':5'-monophosphate metabolism in Yoshida ascites sarcoma cells. Prostaglandin E1 (2.5 mug/ml) enhanced the level of cyclic adenosine 3':5'-monophosphate (cyclic AMP) three to four times in Yoshida ascites sarcoma (YS) cells cultured in vitro. When Ricinus communis toxin (RC-toxin) was added 30 min after the addition of prostaglandin E1, the enhanced level of cyclic AMP in the YS cells decreased rapidly. Of RC-toxin, 0.2 mug/ml was enough to produce the maximum effect. By addition of 5 mM lactose with RC-toxin, approximately 60% of the RC-toxin effect on the levels of cyclic AMP was abolished. This indicates that the specific binding of RC-toxin on the surface membrane is largely responsible for the observed decrease of the cyclic AMP level. The toxin treatment did not induce either leakage of cyclic AMP from the cell or change in the activity of cyclic AMP phosphodiesterase. However, the treatment of YS cells with RC-toxin caused a decrease of adenylate cyclase activity when the activity was measured at a substrate concentration of 0.15 mM ATP. In contrast, there was little difference with the control when the activity was assayed at a higher ATP concentration, 0.24 mM. It was found that the K-m of adenylate cyclase for ATP was changed by RC-toxin from 0.1 to 0.25 mM, and that the Mg2+ activation of the enzyme observable in untreated cells disappeared. These results suggested that the decrease in the level of cyclic AMP in YS cells induced by RC-toxin can be explained in terms of the change in K-m of the adenylate cyclase activity."} {"id": "PMID:164449", "title": "The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). I. The amino acid sequence of cyanogen bromide fragment II.", "content": "Apolipoprotein glutamine I (apoLP-Gln-I or apoA-I) is one of the major protein constituents of human plasma high density lipoproteins. The protein has 245 amino acid residues, including 3 residues of methionine, and is lacking isoleucine, cystine, and cysteine. Cleavage of apoLP-Gln-I with cyanogen bromide yields four fragments, designated in their order of elution from Bio-Gel P-30 as CNBr I, II, III, and IV. In the present study, we report the complete amino acid sequence of the NH2-terminal fragment, CNBr II, a peptide that contains 90 amino acid residues.", "contents": "The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). I. The amino acid sequence of cyanogen bromide fragment II. Apolipoprotein glutamine I (apoLP-Gln-I or apoA-I) is one of the major protein constituents of human plasma high density lipoproteins. The protein has 245 amino acid residues, including 3 residues of methionine, and is lacking isoleucine, cystine, and cysteine. Cleavage of apoLP-Gln-I with cyanogen bromide yields four fragments, designated in their order of elution from Bio-Gel P-30 as CNBr I, II, III, and IV. In the present study, we report the complete amino acid sequence of the NH2-terminal fragment, CNBr II, a peptide that contains 90 amino acid residues."} {"id": "PMID:164450", "title": "The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). II. The amino acid sequence and alignment of cyanogen bromide fragments IV, III, and I.", "content": "Apolipoprotein glutamine I (apoLP-Gln-I or apoA-I) is the major protein constituent of the human plasma high density lipoproteins. Cleavage of this protein with cyanogen bromide yields four fragments, designated in the order of elution from Bio-Gel P-30 as CNBr I, II, III, and IV. In the first paper in this series, the amino acid sequence of the NH2-terminal fragment, CNBr II, is reported. In the present study, CNBr IV, III, and I, containing, respectively, 25, 36, and 94 amino acids were sequenced by conventional means. To establish the alignment of the cyanogen bromide fragments, apoLP-Gln-I was digested with trypsin and two of the three methionine-containing tryptic peptides were isolated. The amino acid sequence of apoLP-Gln-I is as follows: (see article). With the complete amino acid sequence available, a CPK space-filling model of apoLP-Gln-I was constructed. The protein was placed into an alpha helical conformation wherever the primary structure permitted. Thirteen helical regions were identified. These regions account for 70% of the amino acid residues of the protein. Each helix is characterized as having two faces (amphipathic). One is a polar face that occupies approximately 180 degrees of the surface of the helix and the other is a hydrophobic face that occupies the other 180 degrees of the helical surface. Similar amphipathic helices have been identified previously in the other lipoprotein-proteins that have known sequences. It is suggested that the amphipathic helical regions of apoLP-Gln-I are important in the binding of phospholipids in high density lipoproteins.", "contents": "The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). II. The amino acid sequence and alignment of cyanogen bromide fragments IV, III, and I. Apolipoprotein glutamine I (apoLP-Gln-I or apoA-I) is the major protein constituent of the human plasma high density lipoproteins. Cleavage of this protein with cyanogen bromide yields four fragments, designated in the order of elution from Bio-Gel P-30 as CNBr I, II, III, and IV. In the first paper in this series, the amino acid sequence of the NH2-terminal fragment, CNBr II, is reported. In the present study, CNBr IV, III, and I, containing, respectively, 25, 36, and 94 amino acids were sequenced by conventional means. To establish the alignment of the cyanogen bromide fragments, apoLP-Gln-I was digested with trypsin and two of the three methionine-containing tryptic peptides were isolated. The amino acid sequence of apoLP-Gln-I is as follows: (see article). With the complete amino acid sequence available, a CPK space-filling model of apoLP-Gln-I was constructed. The protein was placed into an alpha helical conformation wherever the primary structure permitted. Thirteen helical regions were identified. These regions account for 70% of the amino acid residues of the protein. Each helix is characterized as having two faces (amphipathic). One is a polar face that occupies approximately 180 degrees of the surface of the helix and the other is a hydrophobic face that occupies the other 180 degrees of the helical surface. Similar amphipathic helices have been identified previously in the other lipoprotein-proteins that have known sequences. It is suggested that the amphipathic helical regions of apoLP-Gln-I are important in the binding of phospholipids in high density lipoproteins."} {"id": "PMID:164451", "title": "Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture.", "content": "A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP.", "contents": "Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP."} {"id": "PMID:164452", "title": "The hormonal control of gluconeogenesis by regulation of mitochondrial pyruvate carboxylation in isolated rat liver cells.", "content": "The possibility that hormones control hepatic gluconeogenesis via the regulation of the rate of mitochondrial pyruvate carboxylation was investigated with the use of suspensions of liver cells isolated from fasted rats. The mitochondria prepared from liver cells were judged in good condition as they exhibited satisfactory phosphorus-oxygen and respiratory control ratios and transported Ca2+ and K+ ions in an energy-dependent manner. Addition of glucagon, epinephrine, or cyclic adenosine 3':5'-monophosphate to liver cells caused a 50 to 80% increase in the rate of glucose synthesis from lactate. When mitochondria were isolated from the cells after treatment with these agonists, they displayed 2- to 3-fold increases in the rate of pyruvate carboxylation, pyruvate decarboxylation, and pyruvate uptake. These mitochondrial changes are similar to those obtained in hepatic mitochondria prepared from intact, hormone-treated rats. The mitochondrial responses were specific for agents that stimulated gluconeogenesis; no response occurred with 5'-AMP or cyclic adenosine 2':3'-monophosphate. In the cell suspensions, the dose response curves for the activation of mitochondrial pyruvate metabolism and for increased glucose synthesis from L-lactate were coincident with four different agonists. The mitochondrial changes resulting from stimulation with glucagon developed in 1 to 2 min after the rise in cyclic adenosine 3':5'-monophosphate and occurred at least as early as the increase in the rate of gluconeogenesis. When the intracellular level of cyclic adenosine 3':5'-monophosphate returned to basal values, the rates of mitochondrial pyruvate carboxylation and glucose synthesis also declined to control levels. It is concluded that the rate of mitochondrial pyruvate metabolisms can be increased by hormones and cyclic nucleotides and that control of mitochondrial pyruvate carboxylation is an important regulatory site of hepatic gluconeogenesis.", "contents": "The hormonal control of gluconeogenesis by regulation of mitochondrial pyruvate carboxylation in isolated rat liver cells. The possibility that hormones control hepatic gluconeogenesis via the regulation of the rate of mitochondrial pyruvate carboxylation was investigated with the use of suspensions of liver cells isolated from fasted rats. The mitochondria prepared from liver cells were judged in good condition as they exhibited satisfactory phosphorus-oxygen and respiratory control ratios and transported Ca2+ and K+ ions in an energy-dependent manner. Addition of glucagon, epinephrine, or cyclic adenosine 3':5'-monophosphate to liver cells caused a 50 to 80% increase in the rate of glucose synthesis from lactate. When mitochondria were isolated from the cells after treatment with these agonists, they displayed 2- to 3-fold increases in the rate of pyruvate carboxylation, pyruvate decarboxylation, and pyruvate uptake. These mitochondrial changes are similar to those obtained in hepatic mitochondria prepared from intact, hormone-treated rats. The mitochondrial responses were specific for agents that stimulated gluconeogenesis; no response occurred with 5'-AMP or cyclic adenosine 2':3'-monophosphate. In the cell suspensions, the dose response curves for the activation of mitochondrial pyruvate metabolism and for increased glucose synthesis from L-lactate were coincident with four different agonists. The mitochondrial changes resulting from stimulation with glucagon developed in 1 to 2 min after the rise in cyclic adenosine 3':5'-monophosphate and occurred at least as early as the increase in the rate of gluconeogenesis. When the intracellular level of cyclic adenosine 3':5'-monophosphate returned to basal values, the rates of mitochondrial pyruvate carboxylation and glucose synthesis also declined to control levels. It is concluded that the rate of mitochondrial pyruvate metabolisms can be increased by hormones and cyclic nucleotides and that control of mitochondrial pyruvate carboxylation is an important regulatory site of hepatic gluconeogenesis."} {"id": "PMID:164453", "title": "Superoxide dismutases from a blue-green alga, Plectonema boryanum.", "content": "Iron-containing and manganese-containing superoxide dismutases were found in Plectonema boryanum. The Mn-enzyme occupies about 10% of total activity. The Fe-enzyme was purified to near homogeneity. It contains 2 atoms of iron per mol. Its molecular weight is 41,700 and it is composed of two subunits of identical molecular weight without disulfide linkage. Amino acid composition is presented. Electron paramagnetic resonance spectrum revealed that iron occurs in a high spin ferric form and in some anisotropic environment. The absorption spectrum and the absence of acid-labile enzymes are insensitive to cyanide. Although the Fe-enzyme is sensitive to hydrogen peroxide, the Mn-enzyme is not.", "contents": "Superoxide dismutases from a blue-green alga, Plectonema boryanum. Iron-containing and manganese-containing superoxide dismutases were found in Plectonema boryanum. The Mn-enzyme occupies about 10% of total activity. The Fe-enzyme was purified to near homogeneity. It contains 2 atoms of iron per mol. Its molecular weight is 41,700 and it is composed of two subunits of identical molecular weight without disulfide linkage. Amino acid composition is presented. Electron paramagnetic resonance spectrum revealed that iron occurs in a high spin ferric form and in some anisotropic environment. The absorption spectrum and the absence of acid-labile enzymes are insensitive to cyanide. Although the Fe-enzyme is sensitive to hydrogen peroxide, the Mn-enzyme is not."} {"id": "PMID:164454", "title": "The ultraviolet endonuclease of bacteriophage T4. Further characterization.", "content": "The T4 ultraviolet endonuclease was previously shown to produce strand incisions (nicks) in ultraviolet-irradiated DNA on the 5' side of thymine dimers. The present studies demonstrate that the purified endonuclease creates 3'-OH and 5'-P termini at the sites of nicking. Photoreactivation of ultraviolet-sensitive sites, thereby demonstrating directly endonucleause has a molecular weight of approximately 18,000 and attacks ultraviolet-irradiated single-stranded Escherichia coli and M-13 DNA.", "contents": "The ultraviolet endonuclease of bacteriophage T4. Further characterization. The T4 ultraviolet endonuclease was previously shown to produce strand incisions (nicks) in ultraviolet-irradiated DNA on the 5' side of thymine dimers. The present studies demonstrate that the purified endonuclease creates 3'-OH and 5'-P termini at the sites of nicking. Photoreactivation of ultraviolet-sensitive sites, thereby demonstrating directly endonucleause has a molecular weight of approximately 18,000 and attacks ultraviolet-irradiated single-stranded Escherichia coli and M-13 DNA."} {"id": "PMID:164455", "title": "Glucocorticoid receptors in lung. Mechanism of specific glucocorticoid uptake by fetal rabbit lung nuclei.", "content": "After exposure of fetal rabbit lungs to glucocorticoid in vivo or in vitro, the hormone binds to specific receptors localized in the cytoplasm and in the nuclei. The present studies are compatible with a mechanism by which the nuclear receptor originates from the cytoplasm and arises from a hormone-, temperature-, and ionic strength-dependent transfer of the cytoplasmic receptor into the nucleus. This conclusion is reached from the following observations. Specific binding of glucocorticoid to nuclei from lungs not previously exposed to the hormone is not observed unless the cytosol is also present. In the presence of cytosol, nuclear uptake of the hormone is very slow at 0 degrees but is highly enhanced with increasing temperature. Concomitantly with the increased nuclear uptake there is an equiivalent loss of glucocortoid-receptor complex from the cytosol, indicating that the complex is transferred to the nuclei by a temperature-dependent process. Although the nuclei do not bind the cytoplasmic complex at 0 degrees, they do so provided that the cytosol is briefly heated in the presence of hormone prior to mixing with the nuclei. Thus the cytoplasmic complex must first be activated before it can bind to nuclei..", "contents": "Glucocorticoid receptors in lung. Mechanism of specific glucocorticoid uptake by fetal rabbit lung nuclei. After exposure of fetal rabbit lungs to glucocorticoid in vivo or in vitro, the hormone binds to specific receptors localized in the cytoplasm and in the nuclei. The present studies are compatible with a mechanism by which the nuclear receptor originates from the cytoplasm and arises from a hormone-, temperature-, and ionic strength-dependent transfer of the cytoplasmic receptor into the nucleus. This conclusion is reached from the following observations. Specific binding of glucocorticoid to nuclei from lungs not previously exposed to the hormone is not observed unless the cytosol is also present. In the presence of cytosol, nuclear uptake of the hormone is very slow at 0 degrees but is highly enhanced with increasing temperature. Concomitantly with the increased nuclear uptake there is an equiivalent loss of glucocortoid-receptor complex from the cytosol, indicating that the complex is transferred to the nuclei by a temperature-dependent process. Although the nuclei do not bind the cytoplasmic complex at 0 degrees, they do so provided that the cytosol is briefly heated in the presence of hormone prior to mixing with the nuclei. Thus the cytoplasmic complex must first be activated before it can bind to nuclei.."} {"id": "PMID:164456", "title": "Glucocorticoid receptors in lung. Comparison between nonactivated and activated forms of the cytoplasmic glucocorticoid binding protein and their relationship to the nuclear binding protein of fetal rabbit lung.", "content": "In the absence of salt the cytoplasmic glucocorticoid receptor of fetal rabbit lung sediments at 7 S while the nuclear receptor sediments at 4 S. However, if nuclear extracts are mixed with receptor-depleted cytosol preparations in dilute buffer solutions without added salt, the nuclear 4 S receptor sediments as a 7 S species similar to that observed for the cytoplasmic form under the same conditions suggesting an interaction of the nuclear receptor with other cytosol proteins rather than with itself. In addition, both cytoplasmic and nuclear receptors sediment at 4 S in 0.4 M KCl and a major fraction of the nuclear receptor has an agarose elution profile identical to that of the cytoplasmic receptor. Thus a major fraction of the nuclear receptors is indistinguishable from the cytoplasmic receptors by the methods used. Since the cytoplasmic receptor sediments at 4 S in 0.15 M KCl, it is suggested that in vivo the glucocorticoid receptor may exist as a 4 S species and that the 7 S form described previously may result from an interaction of the 4 S component with other cytosol proteins in hypotonic media. About 25% of the receptor present in nuclear extracts has an agarose elution profile different from that of the cytoplasmic receptor in 0.4 M KCl. This suggests that either the nuclear receptor associates with itself or other nuclear proteins or that more than one form of nuclear receptor exists. Earlier observations suggested that in the absence of hormone the glucocorticoid receptor is localized exclusively in the cytoplasm of lung cells and that the nuclear receptor is formed by a transfer of the cytoplasmic steroid-receptor complex into the nucleus. A prerequisite for this transfer seems to be a modification of the receptor to an active form which can bind to nuclei. This receptor transfomration, referred to in this paper as activation of the receptor, can occur in the absence of nuclei and is highly dependent on temperature and ionic strength. Cytoplasmic receptors activated either by heating or by exposure to high ionic strength are indistinguishable from nonactivated receptors by sucrose density gradient analysis or by agarose gel filtration in solutions containing 0.4 M KCl. Simiarly, no significant difference in the absence of salt is observed after activation by heating. These results suggest that activation of the cytoplasmic glucocorticoid receptor involves conformational changes which favor its transfer and/or binding to nuclear sites rather than conversion of a 4 S species to a faster-sedimenting form by dimerization or by addition of another protein unit as has been proposed for the activation of the estrogen receptor of the rat uterus.", "contents": "Glucocorticoid receptors in lung. Comparison between nonactivated and activated forms of the cytoplasmic glucocorticoid binding protein and their relationship to the nuclear binding protein of fetal rabbit lung. In the absence of salt the cytoplasmic glucocorticoid receptor of fetal rabbit lung sediments at 7 S while the nuclear receptor sediments at 4 S. However, if nuclear extracts are mixed with receptor-depleted cytosol preparations in dilute buffer solutions without added salt, the nuclear 4 S receptor sediments as a 7 S species similar to that observed for the cytoplasmic form under the same conditions suggesting an interaction of the nuclear receptor with other cytosol proteins rather than with itself. In addition, both cytoplasmic and nuclear receptors sediment at 4 S in 0.4 M KCl and a major fraction of the nuclear receptor has an agarose elution profile identical to that of the cytoplasmic receptor. Thus a major fraction of the nuclear receptors is indistinguishable from the cytoplasmic receptors by the methods used. Since the cytoplasmic receptor sediments at 4 S in 0.15 M KCl, it is suggested that in vivo the glucocorticoid receptor may exist as a 4 S species and that the 7 S form described previously may result from an interaction of the 4 S component with other cytosol proteins in hypotonic media. About 25% of the receptor present in nuclear extracts has an agarose elution profile different from that of the cytoplasmic receptor in 0.4 M KCl. This suggests that either the nuclear receptor associates with itself or other nuclear proteins or that more than one form of nuclear receptor exists. Earlier observations suggested that in the absence of hormone the glucocorticoid receptor is localized exclusively in the cytoplasm of lung cells and that the nuclear receptor is formed by a transfer of the cytoplasmic steroid-receptor complex into the nucleus. A prerequisite for this transfer seems to be a modification of the receptor to an active form which can bind to nuclei. This receptor transfomration, referred to in this paper as activation of the receptor, can occur in the absence of nuclei and is highly dependent on temperature and ionic strength. Cytoplasmic receptors activated either by heating or by exposure to high ionic strength are indistinguishable from nonactivated receptors by sucrose density gradient analysis or by agarose gel filtration in solutions containing 0.4 M KCl. Simiarly, no significant difference in the absence of salt is observed after activation by heating. These results suggest that activation of the cytoplasmic glucocorticoid receptor involves conformational changes which favor its transfer and/or binding to nuclear sites rather than conversion of a 4 S species to a faster-sedimenting form by dimerization or by addition of another protein unit as has been proposed for the activation of the estrogen receptor of the rat uterus."} {"id": "PMID:164457", "title": "Catabolism of photo-oxidized and desialylated hemopexin in the rabbit.", "content": "Following injection of rabbit 125I-asialohemopexin, more than 90% of the protein-bound 125I was removed from the circulation of rabbits within 12 min. The amount of asialoprotein in the catabolic compartment reached a peak concentration (75 to 85%) 12 min after injection and was completely eliminated from this compartment within 2 hours. The degradation products were excreted into the urine, with 50 to 70% of the 125I eliminated during the first 24 hours and 90 to 95% excreted by 48 hours. Analysis of these data indicated an apparent first order rate constant for uptake of asialohemopexin of 0.32 min-1, for catabolism of 0.020 min-1 and for excretion of 0.054 to 0.093 hour-1. The plasma distribution curves of 125I-hemopexin, after the first 24 hours, showed essentially no difference. Both proteins were catabolized with an average T1/2 of 25 to 26 hours and a similar fractional catabolic rate. Simultaneous injection of heme and 125I-hemopexin resulted in rapid removal and catabolism of the protein. In contrast, injection of heme had little if any effect on the plasma radioactivity curve of photoinactivated 125I-hemopexin.", "contents": "Catabolism of photo-oxidized and desialylated hemopexin in the rabbit. Following injection of rabbit 125I-asialohemopexin, more than 90% of the protein-bound 125I was removed from the circulation of rabbits within 12 min. The amount of asialoprotein in the catabolic compartment reached a peak concentration (75 to 85%) 12 min after injection and was completely eliminated from this compartment within 2 hours. The degradation products were excreted into the urine, with 50 to 70% of the 125I eliminated during the first 24 hours and 90 to 95% excreted by 48 hours. Analysis of these data indicated an apparent first order rate constant for uptake of asialohemopexin of 0.32 min-1, for catabolism of 0.020 min-1 and for excretion of 0.054 to 0.093 hour-1. The plasma distribution curves of 125I-hemopexin, after the first 24 hours, showed essentially no difference. Both proteins were catabolized with an average T1/2 of 25 to 26 hours and a similar fractional catabolic rate. Simultaneous injection of heme and 125I-hemopexin resulted in rapid removal and catabolism of the protein. In contrast, injection of heme had little if any effect on the plasma radioactivity curve of photoinactivated 125I-hemopexin."} {"id": "PMID:164458", "title": "Selective retention and formation of a delta5-androstenediol-receptor complex in cell nuclei of the rat vagina.", "content": "Cellular protein binding of a number of androstene and androstane derivatives that promote the growth of the vagina in rats has been studied. It was found that cell nuclei of the rat vagina contain a tissue-specific protein that binds 3beta,17beta-dihydroxy-androst-5-ene (delta5-androstenediol), a unique steroid causing growth and keratinization of the vaginal epithelium. The formation of the steroid-protein complex can be demonstrated by the administration of delta5-[3H]androstenediol to ovariectomized rats or by the incubation of minced vagina with the radioactive steroid. The steroid can interact with purified vaginal cell nuclei even in the absence of a cytosol preparation, forming the same steroid-protein complex. The formation of the complex is temperature-dependent; it occurs much more readily at 37 degrees than at 0 degrees. The delta5-[3H]androstenediol-protein complex migrated as about 4 S in a sucrose gradient medium containing 0.4 M KCl. A similar complex can be detected when nuclei of vaginal cells are incubated with 3alpha,17beta-dihydroxy-5alpha-androstane, 3beta,17beta-dihydroxy-5alpha-androstane, and 3beta-hydroxy-androst-5-en-17-one which also have the capability of stimulating vaginal epithelium, although in somewhat different ways. These steroids may bind to different groups of chromatin-bound receptor proteins in various layers of vaginal epithelium. The delta5-androstenediol binding protein is not found in the vaginal cytosol fraction that contains receptor proteins for estrogens and progestins, nor in the cytosol or nuclei of rat uterus cells, but not in muscle, brain, kidney, or liver. Testosterone and 5alpha-dihydrostestosterone bind weakly to the protein, whereas cortisol, androstenedione, 17beta-estradiol, and progesterone do not bind to the same protein by any significant extent.", "contents": "Selective retention and formation of a delta5-androstenediol-receptor complex in cell nuclei of the rat vagina. Cellular protein binding of a number of androstene and androstane derivatives that promote the growth of the vagina in rats has been studied. It was found that cell nuclei of the rat vagina contain a tissue-specific protein that binds 3beta,17beta-dihydroxy-androst-5-ene (delta5-androstenediol), a unique steroid causing growth and keratinization of the vaginal epithelium. The formation of the steroid-protein complex can be demonstrated by the administration of delta5-[3H]androstenediol to ovariectomized rats or by the incubation of minced vagina with the radioactive steroid. The steroid can interact with purified vaginal cell nuclei even in the absence of a cytosol preparation, forming the same steroid-protein complex. The formation of the complex is temperature-dependent; it occurs much more readily at 37 degrees than at 0 degrees. The delta5-[3H]androstenediol-protein complex migrated as about 4 S in a sucrose gradient medium containing 0.4 M KCl. A similar complex can be detected when nuclei of vaginal cells are incubated with 3alpha,17beta-dihydroxy-5alpha-androstane, 3beta,17beta-dihydroxy-5alpha-androstane, and 3beta-hydroxy-androst-5-en-17-one which also have the capability of stimulating vaginal epithelium, although in somewhat different ways. These steroids may bind to different groups of chromatin-bound receptor proteins in various layers of vaginal epithelium. The delta5-androstenediol binding protein is not found in the vaginal cytosol fraction that contains receptor proteins for estrogens and progestins, nor in the cytosol or nuclei of rat uterus cells, but not in muscle, brain, kidney, or liver. Testosterone and 5alpha-dihydrostestosterone bind weakly to the protein, whereas cortisol, androstenedione, 17beta-estradiol, and progesterone do not bind to the same protein by any significant extent."} {"id": "PMID:164459", "title": "Guanosine monophosphate synthetase from Escherichia coli B-96. Inhibition by nucleosides.", "content": "The mechanism of inhibition of GMP synthetase by purine and purine-analog nucleosides was investigated. It was found that in addition to allowing the nucleoside to bind to the enzyme (Udaka, S., and Moyed, H. S. (1963) J. Biol. Chem. 238, 2797)PPi was also a competitive inhibitor with respect to ATP. A rate equation was derived to describe this inhibitory model for two competitive inhibitors where the binding of one inhibitor is contingent upon the binding of the other. The inhibition constants for a large number of nucleosides were then determined. It was found that the initial enzyme-inhibitor complex (of all nucleoside inhibitors) was slowly (0.2 min-1) transformed into a secondary (nondissociating) complex. The two inhibitory complexes appeared to exist in equilibrium. While decoyenine, N6-allyladenosine, and adenosine had similar inhibition constants for the initial complex (0.7 to 1.0 muM), their apparent inhibition constants for the secondary complex were 0.004, 0.06, and 0.5 muM respectively. These differences in the apparent dissociation constants from the secondary complexes are due to different equilibria between the initial and the secondary complexes. The ratios of the secondary complex to the initial complex at equilibrium were 3,250, 290, and 11 for decovenine, N6-allyladenosine, and adenosine, respectively.", "contents": "Guanosine monophosphate synthetase from Escherichia coli B-96. Inhibition by nucleosides. The mechanism of inhibition of GMP synthetase by purine and purine-analog nucleosides was investigated. It was found that in addition to allowing the nucleoside to bind to the enzyme (Udaka, S., and Moyed, H. S. (1963) J. Biol. Chem. 238, 2797)PPi was also a competitive inhibitor with respect to ATP. A rate equation was derived to describe this inhibitory model for two competitive inhibitors where the binding of one inhibitor is contingent upon the binding of the other. The inhibition constants for a large number of nucleosides were then determined. It was found that the initial enzyme-inhibitor complex (of all nucleoside inhibitors) was slowly (0.2 min-1) transformed into a secondary (nondissociating) complex. The two inhibitory complexes appeared to exist in equilibrium. While decoyenine, N6-allyladenosine, and adenosine had similar inhibition constants for the initial complex (0.7 to 1.0 muM), their apparent inhibition constants for the secondary complex were 0.004, 0.06, and 0.5 muM respectively. These differences in the apparent dissociation constants from the secondary complexes are due to different equilibria between the initial and the secondary complexes. The ratios of the secondary complex to the initial complex at equilibrium were 3,250, 290, and 11 for decovenine, N6-allyladenosine, and adenosine, respectively."} {"id": "PMID:164460", "title": "Intracellular localization of the 3-hydroxy-3-methylglutaryl coenzme A cycle enzymes in liver. Separate cytoplasmic and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A generating systems for cholesterogenesis and ketogenesis.", "content": "Acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl coenzyme synthase which comprise the 3-hydroxy-3-methylglutaryl-CoA-generating system(s) for hepatic cholesterogenesis and ketogenesis exhibit dual mitochondrial and cytoplasmic localization. Twenty to forty per cent of the thiolase and synthase of avian and rat liver are localized in the cytoplasmic compartment, the remainder residing in the mitochondria. In contrast, 3-hydroxy-3 methylglutaryl-CoA lyase, an enzyme unique to the \"3-hydroxy-3-methylglutaryl-CoA cycle\" of ketogenesis, appears to be localized in the mitochondrion. The small proportion, 4 to 8 percent, of this enzyme found in the cytoplasmic fraction appears to arise via leakage from the mitochondria during cell fractionation in that its properties, pI and stability, are identical to those of the mitochondrial lyase. These results are consistent with the view that ketogenesis which involves all three enzymes, acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA lyase, occurs exclusively in the mitochondrion, whereas cholesterogenesis, a pathway which involves only the 3-hydroxy-3-methylglutaryl-CoA synthesizing enzymes, is restricted to the cytoplasm. Further fractionation of isolated mitochondria from chicken and rat liver showed that all three of the 3-hydroxy-3-methylglutaryl-CoA cycle enzymes are soluble and are localized within the matrix compartment of the mitochondrion. Likewise, cytoplasmic acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase are soluble cytosolic enzymes, no thiolase or synthase activity being detectable in the microsomal fraction. Chicken liver mitochondrial 3-hydroxy-3methylglutaryl-CoA synthase activity consists of a single enzymic species with a pI of 7.2, whereas the cytoplasmic activity is composed of at least two species with pI values of 4.8 and 6.7. Thus it is evident that the mitochondrial and cytoplasmic species are molecularly distinct as has been shown to be the case for the mitochondrial and cytoplasmic acetoacetyl-CoA thiolases from avian liver (Clinkenbeard, K. D., Sugiyama, T., Moss, J., Reed, W. D., and Lane, M. D. (1973) J. Biol. Chem. 248, 2275). Substantial mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase activity is present in all tissues surveyed, while only liver and kidney possess significant mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity. Therefore, it is proposed that tissues other than liver and kidney are unable to generate acetoacetate because they lack the mitochondrial synthase.", "contents": "Intracellular localization of the 3-hydroxy-3-methylglutaryl coenzme A cycle enzymes in liver. Separate cytoplasmic and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A generating systems for cholesterogenesis and ketogenesis. Acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl coenzyme synthase which comprise the 3-hydroxy-3-methylglutaryl-CoA-generating system(s) for hepatic cholesterogenesis and ketogenesis exhibit dual mitochondrial and cytoplasmic localization. Twenty to forty per cent of the thiolase and synthase of avian and rat liver are localized in the cytoplasmic compartment, the remainder residing in the mitochondria. In contrast, 3-hydroxy-3 methylglutaryl-CoA lyase, an enzyme unique to the \"3-hydroxy-3-methylglutaryl-CoA cycle\" of ketogenesis, appears to be localized in the mitochondrion. The small proportion, 4 to 8 percent, of this enzyme found in the cytoplasmic fraction appears to arise via leakage from the mitochondria during cell fractionation in that its properties, pI and stability, are identical to those of the mitochondrial lyase. These results are consistent with the view that ketogenesis which involves all three enzymes, acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA lyase, occurs exclusively in the mitochondrion, whereas cholesterogenesis, a pathway which involves only the 3-hydroxy-3-methylglutaryl-CoA synthesizing enzymes, is restricted to the cytoplasm. Further fractionation of isolated mitochondria from chicken and rat liver showed that all three of the 3-hydroxy-3-methylglutaryl-CoA cycle enzymes are soluble and are localized within the matrix compartment of the mitochondrion. Likewise, cytoplasmic acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase are soluble cytosolic enzymes, no thiolase or synthase activity being detectable in the microsomal fraction. Chicken liver mitochondrial 3-hydroxy-3methylglutaryl-CoA synthase activity consists of a single enzymic species with a pI of 7.2, whereas the cytoplasmic activity is composed of at least two species with pI values of 4.8 and 6.7. Thus it is evident that the mitochondrial and cytoplasmic species are molecularly distinct as has been shown to be the case for the mitochondrial and cytoplasmic acetoacetyl-CoA thiolases from avian liver (Clinkenbeard, K. D., Sugiyama, T., Moss, J., Reed, W. D., and Lane, M. D. (1973) J. Biol. Chem. 248, 2275). Substantial mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase activity is present in all tissues surveyed, while only liver and kidney possess significant mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity. Therefore, it is proposed that tissues other than liver and kidney are unable to generate acetoacetate because they lack the mitochondrial synthase."} {"id": "PMID:164461", "title": "Vasopressin-sensitive kidney adenylate cyclase. Structural requirements for attachment to the receptor and enzyme activation: studies with vasopressin analogues.", "content": "Several vasopressin analogues were tested on pig kidney membranes for their ability to activate adenylate cyclase and to inhibit the binding of [8-lysine]vasopressin. Both the adenylate cyclase activation and hormonal binding were measured on the same enzyme preparation and under identical were measured on the same enzyme preparation and under identical experimental conditions. A preincubation period in the presence of hormone allowed the binding process to reach equilibrium. Peptide concentrations causing half-maximal adenylate cyclase activation (apparent Km) were, in the order of decreasing affinity:2.5 to 7.0 to 7.0 times 10-10 M [8-lysine] vasopressin, 3.1 to 4.0 times 10-9 M [8-arginine] vasopressin, 2.0 to 3.0 times 10-9 M [I,6-alpha-deaminocystathionine, 8-ornithine]vasopressin, 3.1 times 10-7 M des-9-glycineamide[8-lysine]vasopressin, 0.5 to 1.0 times 10-6 M[1,6-alpha-deaminocystathionine, 2-0-tert...", "contents": "Vasopressin-sensitive kidney adenylate cyclase. Structural requirements for attachment to the receptor and enzyme activation: studies with vasopressin analogues. Several vasopressin analogues were tested on pig kidney membranes for their ability to activate adenylate cyclase and to inhibit the binding of [8-lysine]vasopressin. Both the adenylate cyclase activation and hormonal binding were measured on the same enzyme preparation and under identical were measured on the same enzyme preparation and under identical experimental conditions. A preincubation period in the presence of hormone allowed the binding process to reach equilibrium. Peptide concentrations causing half-maximal adenylate cyclase activation (apparent Km) were, in the order of decreasing affinity:2.5 to 7.0 to 7.0 times 10-10 M [8-lysine] vasopressin, 3.1 to 4.0 times 10-9 M [8-arginine] vasopressin, 2.0 to 3.0 times 10-9 M [I,6-alpha-deaminocystathionine, 8-ornithine]vasopressin, 3.1 times 10-7 M des-9-glycineamide[8-lysine]vasopressin, 0.5 to 1.0 times 10-6 M[1,6-alpha-deaminocystathionine, 2-0-tert..."} {"id": "PMID:164462", "title": "Analysis of the requirements for parathyroid hormone action in renal membranes with the use of inhibiting analogues.", "content": "Two synthetic analogues of bovine parathyroid hormone (PTH) with NH2-terminal modifications, PTH-(3-34) and [desamino-Ala-1]PTH-(1-34), were found to lack agonist activity but to demonstrate antagonist properties when tested in the rat renal cortical adenylyl cyclase assay in vitro against the native hormone or against PTH-(1-34), the active synthetic NH2-terminal tetratriacontapeptide. The inhibition exhibited by these analogues was proportional in degree to the dose of inhibitor, abolished by oxidation of the analogue, reversible by addition of an excess of active hormone, and specific for parathyroid hormone-stimulated renal adenylyl cyclase. No inhibition of basal or sodium fluoride-stimulated renal adenylyl cyclase could be demonstrated. Two other synthetic bovine analogues, PTH-(13-34) and PTH-(1-26), were devoid of agonist and antagonist properties. The over-all results suggest that the requirements for receptor binding of parathyroid hormone are rather broad. Conformational factors or binding interactions involving specific residues, or both seem to require the entire sequence from residue 3 to residue 27 for receptor binding to occur. A dichotomy between receptor binding and adenylyl cyclase activation was demonstrated only by alterations or deletions involving the first 2 NH2-terminal residues of the hormone and emphasizes the importance of these residues in eliciting the biological activity of parathyroid hormone. The two antagonists, [desamino-Ala-1]PTH-(1-34) and PTH-(3-34), should be useful in further analysis of the initial steps in hormone action.", "contents": "Analysis of the requirements for parathyroid hormone action in renal membranes with the use of inhibiting analogues. Two synthetic analogues of bovine parathyroid hormone (PTH) with NH2-terminal modifications, PTH-(3-34) and [desamino-Ala-1]PTH-(1-34), were found to lack agonist activity but to demonstrate antagonist properties when tested in the rat renal cortical adenylyl cyclase assay in vitro against the native hormone or against PTH-(1-34), the active synthetic NH2-terminal tetratriacontapeptide. The inhibition exhibited by these analogues was proportional in degree to the dose of inhibitor, abolished by oxidation of the analogue, reversible by addition of an excess of active hormone, and specific for parathyroid hormone-stimulated renal adenylyl cyclase. No inhibition of basal or sodium fluoride-stimulated renal adenylyl cyclase could be demonstrated. Two other synthetic bovine analogues, PTH-(13-34) and PTH-(1-26), were devoid of agonist and antagonist properties. The over-all results suggest that the requirements for receptor binding of parathyroid hormone are rather broad. Conformational factors or binding interactions involving specific residues, or both seem to require the entire sequence from residue 3 to residue 27 for receptor binding to occur. A dichotomy between receptor binding and adenylyl cyclase activation was demonstrated only by alterations or deletions involving the first 2 NH2-terminal residues of the hormone and emphasizes the importance of these residues in eliciting the biological activity of parathyroid hormone. The two antagonists, [desamino-Ala-1]PTH-(1-34) and PTH-(3-34), should be useful in further analysis of the initial steps in hormone action."} {"id": "PMID:164463", "title": "Temperature sensitivity of cyclic adenosine 3':5'-monophosphate-binding proteins and the regulation of growth and differentiation in neuroblastoma cells.", "content": "The apparent association constant (K-a) of cAMP to the binding proteins from resistant and nonresistant cells was 7.4 times 10-7 M-1 and 8.2 times 10-7 M-1, respectively, and the specific activity of cAMP BINDING TO THESE PROTEINS WAS SIMILAR FOR BOTH TYPES OF CELLS.", "contents": "Temperature sensitivity of cyclic adenosine 3':5'-monophosphate-binding proteins and the regulation of growth and differentiation in neuroblastoma cells. The apparent association constant (K-a) of cAMP to the binding proteins from resistant and nonresistant cells was 7.4 times 10-7 M-1 and 8.2 times 10-7 M-1, respectively, and the specific activity of cAMP BINDING TO THESE PROTEINS WAS SIMILAR FOR BOTH TYPES OF CELLS."} {"id": "PMID:164464", "title": "The nucleotide sequences of the two glutamine transfer ribonucleic acids from Escherichia coli.", "content": "The nucleotide sequences of the two glutamine tRNA species in Escherichia coli K12 have been determined. Sufficient data was obtained to order unambiguously the products of complete RNase digestion of tRNA2Gln, and all but one oligonucleotide from tRNA1Gln. The sequence of tRNA1Gln was established by analogy with tRNA1Gln, as the two tRNAs are very similar, differing by only 7 residues out of 75. tRNA1Gln has the anticodon NUG, where N is a modified nucleotide which is likely to be a derivative of 2-thiouridine, and is specific for the codon CAA. tRNA1Gln has the anticodon CUG, and is specific for the codon CAG (Folk, W. R., and Yaniv, M. (1972) Nature 237, 165). The complete sequences of the tRNAGln species are: See journal for formula (Unique residues are enclosed in parentheses, with the residue in tRNA1Gln above that in tRNA2Gln.).", "contents": "The nucleotide sequences of the two glutamine transfer ribonucleic acids from Escherichia coli. The nucleotide sequences of the two glutamine tRNA species in Escherichia coli K12 have been determined. Sufficient data was obtained to order unambiguously the products of complete RNase digestion of tRNA2Gln, and all but one oligonucleotide from tRNA1Gln. The sequence of tRNA1Gln was established by analogy with tRNA1Gln, as the two tRNAs are very similar, differing by only 7 residues out of 75. tRNA1Gln has the anticodon NUG, where N is a modified nucleotide which is likely to be a derivative of 2-thiouridine, and is specific for the codon CAA. tRNA1Gln has the anticodon CUG, and is specific for the codon CAG (Folk, W. R., and Yaniv, M. (1972) Nature 237, 165). The complete sequences of the tRNAGln species are: See journal for formula (Unique residues are enclosed in parentheses, with the residue in tRNA1Gln above that in tRNA2Gln.)."} {"id": "PMID:164465", "title": "The reversibility of skeletal muscle pyruvate kinase and an assessment of its capacity to support glyconeogenesis.", "content": "The kinetics of pyruvate phosphorylation by rabbit skeletal muscle pyruvate kinase (EC 2.7.1.40) has been studied with a coupled assay using P-enolpyruvate carboxylase (EC 4.1.1.31) and malate dehydrogenase (EC 1.1.1.37). The reaction sequence is (See journal for formula). Although the equilibrium of the pyruvate kinase reaction by itself strongly favors pyruvate production, the over-all equilibrium of this coupled system favors the depletion of pyruvate, thus greatly reducing the problem of back reaction during the assay. In addition, the oxidation of NADH by malate dehydrogenase makes it possible to monitor the system with a spectrophotometer. The Michaelis constant of pyruvate kinase was found to be 0.9 mM for ATP and 7 mM for pyruvate, values that agree reasonably well with earlier studies using direct assays. However, the maximum velocity is about 6 mumol of pyruvate phosphorylated/min/mg of enzyme, which is very much faster than that indicated by earlier studies. These results suggest that the metabolic significance of the reverse reaction of muscle pyruvate kinase may have been underestimated. In particular, the data given here suggest that its rate in vivo is probably comparable to the observed rate of glycogen synthesis from lactate, making possible glyconeogenesis in muscle by pyruvate kinase reversal without the need for an enzymatic bypass of the kind employed by liver and kidney.", "contents": "The reversibility of skeletal muscle pyruvate kinase and an assessment of its capacity to support glyconeogenesis. The kinetics of pyruvate phosphorylation by rabbit skeletal muscle pyruvate kinase (EC 2.7.1.40) has been studied with a coupled assay using P-enolpyruvate carboxylase (EC 4.1.1.31) and malate dehydrogenase (EC 1.1.1.37). The reaction sequence is (See journal for formula). Although the equilibrium of the pyruvate kinase reaction by itself strongly favors pyruvate production, the over-all equilibrium of this coupled system favors the depletion of pyruvate, thus greatly reducing the problem of back reaction during the assay. In addition, the oxidation of NADH by malate dehydrogenase makes it possible to monitor the system with a spectrophotometer. The Michaelis constant of pyruvate kinase was found to be 0.9 mM for ATP and 7 mM for pyruvate, values that agree reasonably well with earlier studies using direct assays. However, the maximum velocity is about 6 mumol of pyruvate phosphorylated/min/mg of enzyme, which is very much faster than that indicated by earlier studies. These results suggest that the metabolic significance of the reverse reaction of muscle pyruvate kinase may have been underestimated. In particular, the data given here suggest that its rate in vivo is probably comparable to the observed rate of glycogen synthesis from lactate, making possible glyconeogenesis in muscle by pyruvate kinase reversal without the need for an enzymatic bypass of the kind employed by liver and kidney."} {"id": "PMID:164466", "title": "Deinduction of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesis in Reuber H-35 cells.", "content": "The activity of phosphoenolpyruvate carboxykinase (GTP) in Reuber H-35 cells was decreased after the removal of 6-N,2-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) from the medium. The decrease in activity was shown immunochemically to be the result of a rapid cessation in specific enzyme synthesis, occurring with a half-time of 40 min. The removal of dexamethasone, a less potent inducer of the enzyme in these cells, did not effect the activity of P-enolpyruvate carboxykinase or its rate of synthesis. Insulin added to either dibutyryl cyclic AMP or dexamethasone-treated cells produced a decline in specific enzyme synthesis which was not as rapid as that observed upon removal of dibutyryl cyclic AMP. This effect of insulin did not require the presence of glucose in the culture medium. Estimates of the half-life of the mRNA for P-enolpyruvate carboxykinase using actinomycin D and cordycepin suggested that after the inhibition of transcription of mRNA, enzyme synthesis continued for periods considerably longer than that observed after deinduction caused by removal of dibutyryl cyclic AMP. In addition, the synthesis of the enzyme could be restimulated by dibutyryl cyclic AMP in the absence of RNA synthesis. It was proposed that the deinduction of phosphoenolpyruvate carboxykinase in these cells is being regulated at the post-transcriptional or translational level.", "contents": "Deinduction of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesis in Reuber H-35 cells. The activity of phosphoenolpyruvate carboxykinase (GTP) in Reuber H-35 cells was decreased after the removal of 6-N,2-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) from the medium. The decrease in activity was shown immunochemically to be the result of a rapid cessation in specific enzyme synthesis, occurring with a half-time of 40 min. The removal of dexamethasone, a less potent inducer of the enzyme in these cells, did not effect the activity of P-enolpyruvate carboxykinase or its rate of synthesis. Insulin added to either dibutyryl cyclic AMP or dexamethasone-treated cells produced a decline in specific enzyme synthesis which was not as rapid as that observed upon removal of dibutyryl cyclic AMP. This effect of insulin did not require the presence of glucose in the culture medium. Estimates of the half-life of the mRNA for P-enolpyruvate carboxykinase using actinomycin D and cordycepin suggested that after the inhibition of transcription of mRNA, enzyme synthesis continued for periods considerably longer than that observed after deinduction caused by removal of dibutyryl cyclic AMP. In addition, the synthesis of the enzyme could be restimulated by dibutyryl cyclic AMP in the absence of RNA synthesis. It was proposed that the deinduction of phosphoenolpyruvate carboxykinase in these cells is being regulated at the post-transcriptional or translational level."} {"id": "PMID:164467", "title": "Glucocorticoid-receptor interaction and induction of murine mammary tumor virus.", "content": "The relationship between the cellular uptake of glucocorticoid hormones, the binding of these hormones to specific in vitro receptors, and the induction of mouse mammary tumor viruses in an established mouse mammary tumor cell line was highly correlated. These results suggest that the induction of mouse mammary tumor virus by glucocorticoid hormones is a physiological process acting through a mechanism of high affinity, saturable steroid-receptors. A temperature-sensitive or salt-dependent step following glucocorticoid-receptor interaction was required for nuclear uptake of the steroid. Induction studies with different adrenocorticoids indicate that the synthetic glucocorticoid, dexamethasone (1,4-pregnadiene-9-fluor-16alpha-methyl-11beta,17alpha,21-triol-3,20-dione), is the most potent inducer of mouse mammary tumor viruses and all steroids which caused significant induction were glucocorticoids. Other glucocorticoids appear to stimulate murine mammary tumor virus production by a mechanism similar to that of dexamethasone; for example, corticosterone competes with dexamethasone for binding to the glucocorticoid receptor and blocks the uptake of dexamethasone into cells. Progesterone also blocks the cellular uptake of dexamethasone and can bind to the glucocorticoid receptor at low concentrations (10-7 to 10-8 M) but progesterone does not consistently induce virus at hormone concentrations even as high as 10-4 M. Thus, in this system, binding to a cytoplasmic receptor is necessary but not sufficient for induction by glucocorticoids. Estrogens and androgens interfere with receptor binding and cellular uptake of dexamethasone but only at much higher concentration (10-4 M) than progesterone, and do not induce mammary tumor virus production. Although there was a positive correlation between steroid structure, binding, and biologic induction, other factors clearly affect the physiological manifestations of steroid actions. Mouse cells with comparable cytoplasmic receptor levels and comparable nuclear uptake differed absolutely in their degree of murine mammary tumor virus induction following hormone treatment. Although all mouse cells examined contain comparable levels of murine mammary tumor virus DNA, only cells producing constitutive levels of murine mammary tumor virus RNA could be induced to higher levels by a variety of glucocorticoids.", "contents": "Glucocorticoid-receptor interaction and induction of murine mammary tumor virus. The relationship between the cellular uptake of glucocorticoid hormones, the binding of these hormones to specific in vitro receptors, and the induction of mouse mammary tumor viruses in an established mouse mammary tumor cell line was highly correlated. These results suggest that the induction of mouse mammary tumor virus by glucocorticoid hormones is a physiological process acting through a mechanism of high affinity, saturable steroid-receptors. A temperature-sensitive or salt-dependent step following glucocorticoid-receptor interaction was required for nuclear uptake of the steroid. Induction studies with different adrenocorticoids indicate that the synthetic glucocorticoid, dexamethasone (1,4-pregnadiene-9-fluor-16alpha-methyl-11beta,17alpha,21-triol-3,20-dione), is the most potent inducer of mouse mammary tumor viruses and all steroids which caused significant induction were glucocorticoids. Other glucocorticoids appear to stimulate murine mammary tumor virus production by a mechanism similar to that of dexamethasone; for example, corticosterone competes with dexamethasone for binding to the glucocorticoid receptor and blocks the uptake of dexamethasone into cells. Progesterone also blocks the cellular uptake of dexamethasone and can bind to the glucocorticoid receptor at low concentrations (10-7 to 10-8 M) but progesterone does not consistently induce virus at hormone concentrations even as high as 10-4 M. Thus, in this system, binding to a cytoplasmic receptor is necessary but not sufficient for induction by glucocorticoids. Estrogens and androgens interfere with receptor binding and cellular uptake of dexamethasone but only at much higher concentration (10-4 M) than progesterone, and do not induce mammary tumor virus production. Although there was a positive correlation between steroid structure, binding, and biologic induction, other factors clearly affect the physiological manifestations of steroid actions. Mouse cells with comparable cytoplasmic receptor levels and comparable nuclear uptake differed absolutely in their degree of murine mammary tumor virus induction following hormone treatment. Although all mouse cells examined contain comparable levels of murine mammary tumor virus DNA, only cells producing constitutive levels of murine mammary tumor virus RNA could be induced to higher levels by a variety of glucocorticoids."} {"id": "PMID:164468", "title": "Time course of insulin-receptor binding and insulin-induced lipogenesis in isolated rat fat cells.", "content": "1. Isolated rat fat cells were incubated at 37 degrees with [U-14C]-glucose 0.55 mM and 125I-labeled insulin. The amount of receptor-bound 125I-labeled insulin and the rate of insulin-induced 14C-lipid synthesis were assessed during association and dissociation of 125I-labeled insulin. 2. The rate of 14C-lipid synthesis was constant from zero time in the absence of insulin and in the presence of insulin in a high concentration (0.7 muM). With insulin in a low concentration (56 pM) the insulin-induced rate of 14C-lipid synthesis was proportional to the receptor occupancy; the receptor binding reached equilibrium and the rate of 14C-lipid synthesis reached a constant value after 30 to 45 min. With insulin in a concentration of 0.7 nM the rate of 14C-lipid synthesis reached a steady state before equilibrium of the receptor binding was obtained. 3. Ater preincubation with 56 pM 125I-labeled insulin followed by removal of extracellular insulin the decrease in the rate of insulin induced 14C-lipid synthesis followed the decrease in receptor occupancy with a half-time of about 10 min. After preincubation with insulin in concentrations of 0.28, 0.56, and 1.4 nM a maximum rate of 14C-lipid synthesis was maintained for about 8, 15, and 30 min, respectively. 4. The following model is suggested. Binding of insulin to the previously described receptors with a dissociation constant of about 3 nM (Gammeltoft, S., and Gliemann, J. (1973) Biochim. Biophys Acta 320, 16-32) represents the first step in the action of insulin on lipid synthesis from glucose. The receptor occupancy is rate-determining at low concentrations of insulin, i.e. when the occupancy is small (about 2 percent or less). At higher insulin concentrations some other step becomes rate-determining and the higher occupancy at equilibrium therefore causes no further increase in the steady state lipogenesis. However, a high receptor occupancy causes a prolonged maintenance of a maximal (or near-maximal) effect after removal of insulin from the medium.", "contents": "Time course of insulin-receptor binding and insulin-induced lipogenesis in isolated rat fat cells. 1. Isolated rat fat cells were incubated at 37 degrees with [U-14C]-glucose 0.55 mM and 125I-labeled insulin. The amount of receptor-bound 125I-labeled insulin and the rate of insulin-induced 14C-lipid synthesis were assessed during association and dissociation of 125I-labeled insulin. 2. The rate of 14C-lipid synthesis was constant from zero time in the absence of insulin and in the presence of insulin in a high concentration (0.7 muM). With insulin in a low concentration (56 pM) the insulin-induced rate of 14C-lipid synthesis was proportional to the receptor occupancy; the receptor binding reached equilibrium and the rate of 14C-lipid synthesis reached a constant value after 30 to 45 min. With insulin in a concentration of 0.7 nM the rate of 14C-lipid synthesis reached a steady state before equilibrium of the receptor binding was obtained. 3. Ater preincubation with 56 pM 125I-labeled insulin followed by removal of extracellular insulin the decrease in the rate of insulin induced 14C-lipid synthesis followed the decrease in receptor occupancy with a half-time of about 10 min. After preincubation with insulin in concentrations of 0.28, 0.56, and 1.4 nM a maximum rate of 14C-lipid synthesis was maintained for about 8, 15, and 30 min, respectively. 4. The following model is suggested. Binding of insulin to the previously described receptors with a dissociation constant of about 3 nM (Gammeltoft, S., and Gliemann, J. (1973) Biochim. Biophys Acta 320, 16-32) represents the first step in the action of insulin on lipid synthesis from glucose. The receptor occupancy is rate-determining at low concentrations of insulin, i.e. when the occupancy is small (about 2 percent or less). At higher insulin concentrations some other step becomes rate-determining and the higher occupancy at equilibrium therefore causes no further increase in the steady state lipogenesis. However, a high receptor occupancy causes a prolonged maintenance of a maximal (or near-maximal) effect after removal of insulin from the medium."} {"id": "PMID:164469", "title": "Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase.", "content": "Adenylate cyclase in particulate fractions from rat adrenal glands is subject to regulation by purine nucleotides, particularly guanine nucleotides. While GTP activates the enzyme, this effect is not evident in all particulate fractions. Following dialysis of the refractory fractions activation by GTP is observed, an indication that endogenous nucleotides may obscure the effects of added GTP. The analog, guanyl-5'-yl imidodiphosphate (Gpp(NH)p gives considerable more activity than does GTP. GDP, on the other hand, is inhibitory, an effect revealed only in the absence of a nucleotide-regenerating solution. GDP blocks the action of both GTP and Gpp(NH)p. These results show that the gamma-phosphate of the nucleotide is required for but need not be metabolized in the activation process. At low substrate concentration (0.1 mM ATP or adenyl-5'-yl imidodiphosphate) stimulation of the enzyme by ACTH occurs only in the presence of added guanine nucleotide (GTP or Gpp(NH)p); the hormone and nucleotide act synergistically. While both GTP and Gpp(NH)p inhibit fluoride-stimulated activity, the level of fluoride required to demonstrate such inhibition appears not to be related to the level of fluoride required for activation of the enzyme. In the presence of GTP, or GTP plus ACTH, the enzyme exhibits normal Michaelis-Menten kinetics with respect to substrate utilization (K-m equal to 0.16 mM). In the activated state, produced with ACTH plus GTP, the enzyme is less susceptible to inhibition by a species of ATP uncomplexed with Mg2+, but is more susceptible to inhibition by Mg2+. These results demonstrate that fundamental differences exist between different states of the adenylate cyclase. The difficulties in describing kinetically the regulation of adenylate cyclase systems in view of the multiple actions of nucleotides and magnesium are discussed.", "contents": "Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase. Adenylate cyclase in particulate fractions from rat adrenal glands is subject to regulation by purine nucleotides, particularly guanine nucleotides. While GTP activates the enzyme, this effect is not evident in all particulate fractions. Following dialysis of the refractory fractions activation by GTP is observed, an indication that endogenous nucleotides may obscure the effects of added GTP. The analog, guanyl-5'-yl imidodiphosphate (Gpp(NH)p gives considerable more activity than does GTP. GDP, on the other hand, is inhibitory, an effect revealed only in the absence of a nucleotide-regenerating solution. GDP blocks the action of both GTP and Gpp(NH)p. These results show that the gamma-phosphate of the nucleotide is required for but need not be metabolized in the activation process. At low substrate concentration (0.1 mM ATP or adenyl-5'-yl imidodiphosphate) stimulation of the enzyme by ACTH occurs only in the presence of added guanine nucleotide (GTP or Gpp(NH)p); the hormone and nucleotide act synergistically. While both GTP and Gpp(NH)p inhibit fluoride-stimulated activity, the level of fluoride required to demonstrate such inhibition appears not to be related to the level of fluoride required for activation of the enzyme. In the presence of GTP, or GTP plus ACTH, the enzyme exhibits normal Michaelis-Menten kinetics with respect to substrate utilization (K-m equal to 0.16 mM). In the activated state, produced with ACTH plus GTP, the enzyme is less susceptible to inhibition by a species of ATP uncomplexed with Mg2+, but is more susceptible to inhibition by Mg2+. These results demonstrate that fundamental differences exist between different states of the adenylate cyclase. The difficulties in describing kinetically the regulation of adenylate cyclase systems in view of the multiple actions of nucleotides and magnesium are discussed."} {"id": "PMID:164470", "title": "A primer ribonucleic acid for initiation of in vitro Rous sarcarcoma virus deoxyribonucleic acid synthesis.", "content": "The nucleotide sequence of an RNA primer molecule for initiation of Rous sarcoma virus DNA synthesis in vitro has been determined. The sequence can be drawn in a cloverleaf structure typical of tRNAs with an anticodon for tryptophan. Aminoacylation of the molecule confirms that it is tRNA-Trp. The same sequence and aminoacylation results are obtained regardless of whether the RNA is isolated from virions or from cells of chickens, the natural host for this virus. It is the only species of tRNA-Trp that is dectected in chicked cell tRNA.", "contents": "A primer ribonucleic acid for initiation of in vitro Rous sarcarcoma virus deoxyribonucleic acid synthesis. The nucleotide sequence of an RNA primer molecule for initiation of Rous sarcoma virus DNA synthesis in vitro has been determined. The sequence can be drawn in a cloverleaf structure typical of tRNAs with an anticodon for tryptophan. Aminoacylation of the molecule confirms that it is tRNA-Trp. The same sequence and aminoacylation results are obtained regardless of whether the RNA is isolated from virions or from cells of chickens, the natural host for this virus. It is the only species of tRNA-Trp that is dectected in chicked cell tRNA."} {"id": "PMID:164472", "title": "Cyclic AMP, membrane transport and cell division. I. Effects of various chemicals on cyclic AMP levels and rate of transport of neucleosides, hypoxanthine and deoxyglucose in several lines of cultured cells.", "content": "Nutrient transport rates and cyclic AMP levels have been implicated in the regulation of cell proliferation. In the present study, however, changes in intracellular cyclic AMP level in several lines of cultured cells (normal 3T3 and SV40 and polyomavirus-transformed 3T3 cells; 3T6, C6 GLIOMA, MOUSE L, and Novikoff rat hepatoma cells) by treatment with papaverine, prostaglandine E1 or isoproterenol did not correlate with the inhibition of the uridine, hypoxanthine or deoxyglucose transport rates by these chemicals. Transport inhibitions by above chemicals or Persantin or Cytochalasin B occurred in most cell lines in the absence of any measurable change in intracellular cyclic AMP concentration. Furthermore, treatment of several cell lines with 1 mM dibutyryl cyclic AMP had no immediate effect on the transport of uridine, thymidine or deoxyglucose, although the transport capacity of the cells for uridine and thymidine, but not that for deoxyglucose, decreased progressively with time of treatment. We also observed that the uridine transport system of all cell lines derived from 3T3 cells and the hypoxanthine transport system of L cells exhibited high degrees of resistance to inhibition by the various chemicals. On the other hand, deoxyglucose transport was inhibited to about the same extent by these chemicals in all the cell lines investigated.", "contents": "Cyclic AMP, membrane transport and cell division. I. Effects of various chemicals on cyclic AMP levels and rate of transport of neucleosides, hypoxanthine and deoxyglucose in several lines of cultured cells. Nutrient transport rates and cyclic AMP levels have been implicated in the regulation of cell proliferation. In the present study, however, changes in intracellular cyclic AMP level in several lines of cultured cells (normal 3T3 and SV40 and polyomavirus-transformed 3T3 cells; 3T6, C6 GLIOMA, MOUSE L, and Novikoff rat hepatoma cells) by treatment with papaverine, prostaglandine E1 or isoproterenol did not correlate with the inhibition of the uridine, hypoxanthine or deoxyglucose transport rates by these chemicals. Transport inhibitions by above chemicals or Persantin or Cytochalasin B occurred in most cell lines in the absence of any measurable change in intracellular cyclic AMP concentration. Furthermore, treatment of several cell lines with 1 mM dibutyryl cyclic AMP had no immediate effect on the transport of uridine, thymidine or deoxyglucose, although the transport capacity of the cells for uridine and thymidine, but not that for deoxyglucose, decreased progressively with time of treatment. We also observed that the uridine transport system of all cell lines derived from 3T3 cells and the hypoxanthine transport system of L cells exhibited high degrees of resistance to inhibition by the various chemicals. On the other hand, deoxyglucose transport was inhibited to about the same extent by these chemicals in all the cell lines investigated."} {"id": "PMID:164473", "title": "Neoplastic differentiation: interaction of simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro.", "content": "The host-virus interactions of Simian virus 40 (SV40) and polyoma virus (Py) with cell lines established from a teratocarcinoma were studied. The cells utilized in this study were the multipotential stem cell of the teratocarcinoma, embryonal carcinoma, and differentiated cells derived from embryonal carcinoma. Several lines of differentiated cells were established in vitro which included parietal yolk sac, epithelial, and spindle cell types. Embryonal carcinoma cells are not susceptible to infection by either SV40 or Py virus. However, differentiated cells are susceptible to infection by these viruses. The differentiated cells are permissive for Py virus replication and nonpermissive for SV40. Several continuously growing cell lines have been established from the SV40 infected cultures which express T antigen in 100% of the cells. The results indicate that undifferentiated embryonal carcinoma cells and their differentiated progeny respond quite differently to challenge with these two oncogenic DNA viruses.", "contents": "Neoplastic differentiation: interaction of simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro. The host-virus interactions of Simian virus 40 (SV40) and polyoma virus (Py) with cell lines established from a teratocarcinoma were studied. The cells utilized in this study were the multipotential stem cell of the teratocarcinoma, embryonal carcinoma, and differentiated cells derived from embryonal carcinoma. Several lines of differentiated cells were established in vitro which included parietal yolk sac, epithelial, and spindle cell types. Embryonal carcinoma cells are not susceptible to infection by either SV40 or Py virus. However, differentiated cells are susceptible to infection by these viruses. The differentiated cells are permissive for Py virus replication and nonpermissive for SV40. Several continuously growing cell lines have been established from the SV40 infected cultures which express T antigen in 100% of the cells. The results indicate that undifferentiated embryonal carcinoma cells and their differentiated progeny respond quite differently to challenge with these two oncogenic DNA viruses."} {"id": "PMID:164474", "title": "The effect of insulin on basal and hormone-induced elevations of cyclic AMP content in cultured human fibroblasts.", "content": "Studies were carried out on confluent cultures of human fibroblasts to explore the effect of insulin on basal and hormone-induced elevations of intracellular cyclic AMP content during short-term incubations in serum-free medium. Insulin tended to decrease basal levels of cyclic AMP but this was not statistically significant. Similarly, insulin was unable to block the elevations of intracellular cyclic AMP content induced by PGE1, epinephrine and glucagon. Paradoxically, when cells were preincubated with insulin, PGE1-stimulated cyclic AMP elevation was potentiated, possibly because insulin was conserving factors needed for a maximal PGE1 stimulus or retarding the leakage of cAMP itself. The results indicate that insulin has little or no direct effect on cyclic AMP metabolism in cultured human fibroblasts and is consistent with the known insensitivity of these cells to insulin for other parameters.", "contents": "The effect of insulin on basal and hormone-induced elevations of cyclic AMP content in cultured human fibroblasts. Studies were carried out on confluent cultures of human fibroblasts to explore the effect of insulin on basal and hormone-induced elevations of intracellular cyclic AMP content during short-term incubations in serum-free medium. Insulin tended to decrease basal levels of cyclic AMP but this was not statistically significant. Similarly, insulin was unable to block the elevations of intracellular cyclic AMP content induced by PGE1, epinephrine and glucagon. Paradoxically, when cells were preincubated with insulin, PGE1-stimulated cyclic AMP elevation was potentiated, possibly because insulin was conserving factors needed for a maximal PGE1 stimulus or retarding the leakage of cAMP itself. The results indicate that insulin has little or no direct effect on cyclic AMP metabolism in cultured human fibroblasts and is consistent with the known insensitivity of these cells to insulin for other parameters."} {"id": "PMID:164475", "title": "Requirement of bromodeoxyuridine for the maintenance of \"transformed\" characteristics in bromodeoxyuridine dependent cells.", "content": "A bromodeoxyuridine(BUdr) dependent cell line, called B4, Which requires BUdr not only for optimal growth but also for the maintenance of the non-contact inhibited state was described previously. We have now shown that contact inhibition in the B4 cells in the absence of BUdr is associated with a marked decrease in the percent of cells synthesizing DNA. The transition to the contact inhibited state in the absence of BUdr does not seem to be due to changes in cyclic AMP levels. It has also been shown that several but not all of the characteristics which distinguish transformed from untransformed cells also distinguish B4 cells grown in the presence of BUdr from B4 cells grown in the absence of BUdr. In addition to being contact inhibited, B4 cells grown in the absence of BUdr have a higher serum requirement, grow less well in soft agar, and are less agglutinable by wheat germ agglutinin than B4 cells grown in the presence of BUdr. Agglutinability by concanavalin A, however, is the same for B4 cells grown in the presence and absence of BUdr. Dependent cells maintained in the presence of BUdr do not form tumors and it is not yet clear how the transformed characteristics of the dependent cells are related to malignancy.", "contents": "Requirement of bromodeoxyuridine for the maintenance of \"transformed\" characteristics in bromodeoxyuridine dependent cells. A bromodeoxyuridine(BUdr) dependent cell line, called B4, Which requires BUdr not only for optimal growth but also for the maintenance of the non-contact inhibited state was described previously. We have now shown that contact inhibition in the B4 cells in the absence of BUdr is associated with a marked decrease in the percent of cells synthesizing DNA. The transition to the contact inhibited state in the absence of BUdr does not seem to be due to changes in cyclic AMP levels. It has also been shown that several but not all of the characteristics which distinguish transformed from untransformed cells also distinguish B4 cells grown in the presence of BUdr from B4 cells grown in the absence of BUdr. In addition to being contact inhibited, B4 cells grown in the absence of BUdr have a higher serum requirement, grow less well in soft agar, and are less agglutinable by wheat germ agglutinin than B4 cells grown in the presence of BUdr. Agglutinability by concanavalin A, however, is the same for B4 cells grown in the presence and absence of BUdr. Dependent cells maintained in the presence of BUdr do not form tumors and it is not yet clear how the transformed characteristics of the dependent cells are related to malignancy."} {"id": "PMID:164476", "title": "Acetylcholine-induced initiation of thymic lymphoblast DNA synthesis and proliferation.", "content": "Low (5 times 10-9 M to 10-7 M) acetylcholine concentrations cause a calcium-independent stimulation of the initiation of DNA synthesis and proliferation of lymphoblasts which are part of rat thymocyte populations suspended in vitro. A much higher (5 times 10-5 M) acetylcholine concentration also stimulates lymphoblast DNA synthesis and proliferation, but this action is calcium-dependent. This proliferogenic response to acetylcholine is however not clearly mediated by either cyclic GMP or cyclic AMP.", "contents": "Acetylcholine-induced initiation of thymic lymphoblast DNA synthesis and proliferation. Low (5 times 10-9 M to 10-7 M) acetylcholine concentrations cause a calcium-independent stimulation of the initiation of DNA synthesis and proliferation of lymphoblasts which are part of rat thymocyte populations suspended in vitro. A much higher (5 times 10-5 M) acetylcholine concentration also stimulates lymphoblast DNA synthesis and proliferation, but this action is calcium-dependent. This proliferogenic response to acetylcholine is however not clearly mediated by either cyclic GMP or cyclic AMP."} {"id": "PMID:164477", "title": "Genetic and hormonal control of male sexual differentiation.", "content": "Phenotypic sexual differentiation during embryogenesis is a complex process involving the action of at least 18 genes. These genes regulate gonadal differentiation, gonadal hormone formation, and in the male the cellular action of three necessary hormones, namely mullerian regression factor, testosterone, and dihydrotestosterone. Analysis of two of the mutations affecting sexual development is consistent with the thesis that the two androgens testosterone and dihydrotestosterone have separate and specific roles in virilization of the male urogenital tract, testosterone stimulating wolffian duct development and dihydrotestosterone mediating development of the urogenital sinus and external genitalia. In the disorder familial incomplete male pseudohermphroditism, type 2, deficient dihydrotestosterone formation is associated with a selective failure of virilization of the urogenital sinus and external genitalia, whereas the wolffian duct derivatives develop normally. On the other hand, in the testicular feminization syndrome there is a complete failure in the development of the male phenotype, indicating that the primary defect involves an abnormality in some biochemical step that is common to the action of both androgens. Evidence from studies in the submandibular gland of the mouse with testicular feminization suggest that the fundamental defect lies in the translocation and/or nuclear binding of the cytoplasmic androgen receptor. It remains to be proven whether these events in the postnatal, sexually dimorphic submandibular gland of the testicular feminization mouse reflect prenatal events occurring in the urogenital tissues during embryogenesis.", "contents": "Genetic and hormonal control of male sexual differentiation. Phenotypic sexual differentiation during embryogenesis is a complex process involving the action of at least 18 genes. These genes regulate gonadal differentiation, gonadal hormone formation, and in the male the cellular action of three necessary hormones, namely mullerian regression factor, testosterone, and dihydrotestosterone. Analysis of two of the mutations affecting sexual development is consistent with the thesis that the two androgens testosterone and dihydrotestosterone have separate and specific roles in virilization of the male urogenital tract, testosterone stimulating wolffian duct development and dihydrotestosterone mediating development of the urogenital sinus and external genitalia. In the disorder familial incomplete male pseudohermphroditism, type 2, deficient dihydrotestosterone formation is associated with a selective failure of virilization of the urogenital sinus and external genitalia, whereas the wolffian duct derivatives develop normally. On the other hand, in the testicular feminization syndrome there is a complete failure in the development of the male phenotype, indicating that the primary defect involves an abnormality in some biochemical step that is common to the action of both androgens. Evidence from studies in the submandibular gland of the mouse with testicular feminization suggest that the fundamental defect lies in the translocation and/or nuclear binding of the cytoplasmic androgen receptor. It remains to be proven whether these events in the postnatal, sexually dimorphic submandibular gland of the testicular feminization mouse reflect prenatal events occurring in the urogenital tissues during embryogenesis."} {"id": "PMID:164478", "title": "Regulation of sterol synthesis in cultured cells by oxygenated derivatives of cholesterol.", "content": "Sterol synthesis in liver in vivo is regulated at the site of the reaction catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase through a feedback system thought to involve either cholesterol or one or more of the products of its metabolism. Cholesterol feeding results in repression of the synthesis of the enzyme, but inactivation of the enzyme seems to precede repressroblasts is not inhibited by purified exogenous cholesterol. However, derivatives of cholesterol produced by the introduction of a ketone or hydroxyl function in the 7, 20, 22 or 25 positions effectively inhibit sterol synthesis by specifically depressing the level of HMG CoA reductase activity. As a result of this specific effect prolonged incubation of an inhibitory sterol with growing L cells results in depletion of cellular sterol. Growth of the culture then ceases and the cells die unless an appropriate sterol or a sterol precursor is supplied in the medium. The inhibitory sterols, 25-hydroxycholesterol and 7-ketocholesterol appear to be taken up by L cells through processes that involve their specific interactions with saturable cellular receptors. The uptake of cholesterol by L cells appears to be by a different process--possibly through physical diffusion.", "contents": "Regulation of sterol synthesis in cultured cells by oxygenated derivatives of cholesterol. Sterol synthesis in liver in vivo is regulated at the site of the reaction catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase through a feedback system thought to involve either cholesterol or one or more of the products of its metabolism. Cholesterol feeding results in repression of the synthesis of the enzyme, but inactivation of the enzyme seems to precede repressroblasts is not inhibited by purified exogenous cholesterol. However, derivatives of cholesterol produced by the introduction of a ketone or hydroxyl function in the 7, 20, 22 or 25 positions effectively inhibit sterol synthesis by specifically depressing the level of HMG CoA reductase activity. As a result of this specific effect prolonged incubation of an inhibitory sterol with growing L cells results in depletion of cellular sterol. Growth of the culture then ceases and the cells die unless an appropriate sterol or a sterol precursor is supplied in the medium. The inhibitory sterols, 25-hydroxycholesterol and 7-ketocholesterol appear to be taken up by L cells through processes that involve their specific interactions with saturable cellular receptors. The uptake of cholesterol by L cells appears to be by a different process--possibly through physical diffusion."} {"id": "PMID:164479", "title": "Use of mutant fibroblasts in the analysis of the regulation of cholesterol metabolism in human cells.", "content": "Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipoproteins (LDL) has led to the delineation of an important, hitherto unrecognized, regulatory process for cholesterol metabolism. On normal cells, binding of LDL to this receptor regulates cholesterol metabolism by two mechanisms: (a) suppression of cholesterol synthesis and (b) facilitation of the rate of proteolytic degradation of the lipoprotein. In cells from homozygotes with the autosomal dominant disorder Familial Hypercholesterolemia, a nearly total reduction in LDL receptors results in two secondary abnormalities: (a) overproduction of cholesterol due to an inability of LDL to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) impairment in the rate of proteolytic degradation of LDL. Cells from heterozygotes possess about 50 per cent of the normal number of LDL recpetors; this leads to a concentration-dependent defect in regulation, so that attainment of rates of cholesterol synthesis and LDL degradation equal to that in normal cells requires a two to three-fold higher concentration of extracellular LDL in the heterozygote. The identification of this genetic regulatory defect in fibroblasts of heterozygotes with Familial Hypercholesterolemia makes available an in vitro system for studying the molecular mechanism by which a dominant mutation affects gene expression in mammalian cells.", "contents": "Use of mutant fibroblasts in the analysis of the regulation of cholesterol metabolism in human cells. Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipoproteins (LDL) has led to the delineation of an important, hitherto unrecognized, regulatory process for cholesterol metabolism. On normal cells, binding of LDL to this receptor regulates cholesterol metabolism by two mechanisms: (a) suppression of cholesterol synthesis and (b) facilitation of the rate of proteolytic degradation of the lipoprotein. In cells from homozygotes with the autosomal dominant disorder Familial Hypercholesterolemia, a nearly total reduction in LDL receptors results in two secondary abnormalities: (a) overproduction of cholesterol due to an inability of LDL to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) impairment in the rate of proteolytic degradation of LDL. Cells from heterozygotes possess about 50 per cent of the normal number of LDL recpetors; this leads to a concentration-dependent defect in regulation, so that attainment of rates of cholesterol synthesis and LDL degradation equal to that in normal cells requires a two to three-fold higher concentration of extracellular LDL in the heterozygote. The identification of this genetic regulatory defect in fibroblasts of heterozygotes with Familial Hypercholesterolemia makes available an in vitro system for studying the molecular mechanism by which a dominant mutation affects gene expression in mammalian cells."} {"id": "PMID:164480", "title": "Phosphorylation of non-histone proteins in the regulation of chromosome structure and function.", "content": "Non-histone chromosomal proteins are phosphorylated and dephosphorylated within the intact nucleus by two independent sets of reactions, a protein kinase reaction which transfers the terminal phosphate group of a variety of nucleoside and deoxynucleoside triphosphates to serine and threonine residues in the proteins, and a phosphatase reaction which cleaves these phosphoserine and phosphothreonine bonds and releases inorganic phosphate. Several lines of evidence are consistent with the hypothesis that the phosphorylation and dephosphorylation of these proteins is involved in gene control mechanisms, including the findings that phosphorylated non-histone proteins are highly heterogeneous and their phosphorylation patterns are tissue specific, changes in their phosphorylation correlate with changes in chromatin structure and gene acticity, addition of phosphorylated non-histone proteins increases RNA synthesis in vitro. and phosphorylated non-histone proteins bind specifically to DNA. Cyclic AMP has both stimulatory and inhibitory properties on non-histone protein phosphorylation, depending on the enzyme fraction and substrate employed A specific protein component whose phosphorylation is inhibited by cyclic AMP has been found to be associated with RNA polymerase. The cyclic AMP-induced decrease in the phosphorylation of this protein correlates with an enhancement of RNA synthesis in vitro. These results suggest that both phosphorylation and dephosphorylation of chromatin-associated proteins may be involved in the control of gene readout.", "contents": "Phosphorylation of non-histone proteins in the regulation of chromosome structure and function. Non-histone chromosomal proteins are phosphorylated and dephosphorylated within the intact nucleus by two independent sets of reactions, a protein kinase reaction which transfers the terminal phosphate group of a variety of nucleoside and deoxynucleoside triphosphates to serine and threonine residues in the proteins, and a phosphatase reaction which cleaves these phosphoserine and phosphothreonine bonds and releases inorganic phosphate. Several lines of evidence are consistent with the hypothesis that the phosphorylation and dephosphorylation of these proteins is involved in gene control mechanisms, including the findings that phosphorylated non-histone proteins are highly heterogeneous and their phosphorylation patterns are tissue specific, changes in their phosphorylation correlate with changes in chromatin structure and gene acticity, addition of phosphorylated non-histone proteins increases RNA synthesis in vitro. and phosphorylated non-histone proteins bind specifically to DNA. Cyclic AMP has both stimulatory and inhibitory properties on non-histone protein phosphorylation, depending on the enzyme fraction and substrate employed A specific protein component whose phosphorylation is inhibited by cyclic AMP has been found to be associated with RNA polymerase. The cyclic AMP-induced decrease in the phosphorylation of this protein correlates with an enhancement of RNA synthesis in vitro. These results suggest that both phosphorylation and dephosphorylation of chromatin-associated proteins may be involved in the control of gene readout."} {"id": "PMID:164481", "title": "Persistent testicular delta5-isomerase-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) deficiency in the delta5-3beta-HSD form of congenital adrenal hyperplasia.", "content": "A partial testicular defect in testosterone secretion has been documented in a pubertal male with a congenital adrenal hyperplasia due to hereditary deficiency of the delta5-isomerase-3beta-hydroxysteroid dehydrogenase enzyme complex (delta5-3beta-HSD). Diagnosis of the enzymatic defect is based on the clinical picture of ambiguous genitalia and salt-losing crisis in infancy, together with high urinary delta5-pregnenetriol and plasma dehydroepiandrosterone when the patient was taken off replacement corticoid treatment. No hormonal response to ACTH or salt deprivation was demonstrable. In addition, in vivo studies revealed a partial enzymatic defect in the testis. Although plasma testosterone was low-normal (250 ng/100 ml), plasma delta5-androstenediol was markedly elevated and rose to a greater extent than testosterone after human chorionic gonadotropin administration. In vitro testicular incubation studies suggested a testicular delta5-3beta-HSD enzyme defect with less delta4 products formed from delta5 precursors than in a control testis. Histochemical studies of the testis were also consistent with this defect. Testicular biopsy revealed spermatogenic arrest, generally diminished Leydig cells, but with focal areas of Leydig cell hyperplasia as well as benign Leydig cell hyperplasia as well as benign Leudig cell nodules within the spermatic cord. In vivo studies of steroid metabolism suggested intact peripheral or hepatic delta5-3beta-HSD activity. These studies imply that delta5-3beta-HSD activity differs in the gonad, adrenal, and peripheral organs. These findings are compatible with the concept that the enzyme complex consists of subunits and/or that enzymes in these organs are under different genetic control.", "contents": "Persistent testicular delta5-isomerase-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) deficiency in the delta5-3beta-HSD form of congenital adrenal hyperplasia. A partial testicular defect in testosterone secretion has been documented in a pubertal male with a congenital adrenal hyperplasia due to hereditary deficiency of the delta5-isomerase-3beta-hydroxysteroid dehydrogenase enzyme complex (delta5-3beta-HSD). Diagnosis of the enzymatic defect is based on the clinical picture of ambiguous genitalia and salt-losing crisis in infancy, together with high urinary delta5-pregnenetriol and plasma dehydroepiandrosterone when the patient was taken off replacement corticoid treatment. No hormonal response to ACTH or salt deprivation was demonstrable. In addition, in vivo studies revealed a partial enzymatic defect in the testis. Although plasma testosterone was low-normal (250 ng/100 ml), plasma delta5-androstenediol was markedly elevated and rose to a greater extent than testosterone after human chorionic gonadotropin administration. In vitro testicular incubation studies suggested a testicular delta5-3beta-HSD enzyme defect with less delta4 products formed from delta5 precursors than in a control testis. Histochemical studies of the testis were also consistent with this defect. Testicular biopsy revealed spermatogenic arrest, generally diminished Leydig cells, but with focal areas of Leydig cell hyperplasia as well as benign Leydig cell hyperplasia as well as benign Leudig cell nodules within the spermatic cord. In vivo studies of steroid metabolism suggested intact peripheral or hepatic delta5-3beta-HSD activity. These studies imply that delta5-3beta-HSD activity differs in the gonad, adrenal, and peripheral organs. These findings are compatible with the concept that the enzyme complex consists of subunits and/or that enzymes in these organs are under different genetic control."} {"id": "PMID:164482", "title": "Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.", "content": "The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90 percent decrease in the cellular content of cholesteryl esters and a 30 percent decrease in the free cholesterol content. When these lipoprotein-deprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximal effect in elevating cellular sterol content (30 mug/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesteryl esters in normal cells. Furthermore, in fibroblasts from patients with the homozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 mug sterol/ml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Moreover, when considered in light of current concepts of LDL metabolism in intact mammals, the present data suggest that a major function of plasma LDL may be to transport cholesterol from its site of synthesis in liver and intestine to its site of uptake in peripheral tissues.", "contents": "Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts. The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90 percent decrease in the cellular content of cholesteryl esters and a 30 percent decrease in the free cholesterol content. When these lipoprotein-deprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximal effect in elevating cellular sterol content (30 mug/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesteryl esters in normal cells. Furthermore, in fibroblasts from patients with the homozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 mug sterol/ml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Moreover, when considered in light of current concepts of LDL metabolism in intact mammals, the present data suggest that a major function of plasma LDL may be to transport cholesterol from its site of synthesis in liver and intestine to its site of uptake in peripheral tissues."} {"id": "PMID:164483", "title": "Properties of a subpopulation of T cells bearing histamine receptors.", "content": "C57BL/6 mice immunized i.p. with alloantigen (P815 mastocytoma cells) develop cytolytically active thymus-derived (T) splenic lymphocytes. The definition of specific histamine receptor sites on effector T cells has been studied by measuring the in vitro effects of the hormone on cytolytic activity. Histamine was found to inhibit cytolysis reversibly and to increase lymphoid cell cyclic AMP levels. Both of these histamine activities were reversed by burimamide and metiamide; neither activity was affected by diphenhydramine or pyrilamine. These findings indicate that modulation of effector T cell activity by histamine is mediated only by one of the subtypes of tissue histamine receptors, designated a histamine-type 2 receptor. This receptor appears to be present on cytolytically active cells; there is no evidence for activation by histamine of auxiliary or \"suppressor\" cells. The estimated dissociation constant (KB) for the burimamide-receptor complex (9 times 10-minus 6 tm) and for the metiamide-receptor complex (8 times 10-minus 7 M) indicated that the histamine receptor on T cells is quite similar to histamine-type 2 receptors in other tissues. Cells bearing such receptors could not be isolated by passage through a column of histamine-coated tsepharose beads. The cytolytic activity of spleen cells taken from mice early (days 7-9) after immunization is virtually unaffected by histamine in vitro. In contrast, the activity of spleen cells taken from mice later in the immune response is progressively more susceptible to inhibition by histamine. After reaching a maximum at day 11, the spleen cell cytolytic activity falls in a pattern that parallels the increase in susceptibility to histamine. The susceptibility of effector T cells to histamine appears also to reflect their site of origin, for peritoneal exudate effector cells were found to be significantly less sensitive than spleen cells to inhibition by histamine. The progressive increase in inhibition by histamine apparently reflects the appearance of greater numbers of specific histamine-type 2 receptors, and is probably a general phenomenon, for spleen cells from A/J or C3H mice immunized with either P815 mastocytoma (H-2d) or EL-4 (H-2b) cells showed the same effect. However, the appearance of histamine receptors could be altered by prior immunization with an unrelated alloantigen: thus, when A/J mice are preimmunized with EL-4, a subsequent immunization with mastocytoma cells results in peak spleen anti-H-2d activity at day 9 instead of days 11-13, and the appearance of significant (greater than 40 percent) inhibition by histamine as early as day 8 instead of day 16. The physiological role of the histamine receptors is as yet undefined, though their unexpected rate of appearance on effector T cells, coincident with a decline in the number of lytically active cells in vivo, may be a significant hint that hormone receptors play a role in the control of T-cell proliferation.", "contents": "Properties of a subpopulation of T cells bearing histamine receptors. C57BL/6 mice immunized i.p. with alloantigen (P815 mastocytoma cells) develop cytolytically active thymus-derived (T) splenic lymphocytes. The definition of specific histamine receptor sites on effector T cells has been studied by measuring the in vitro effects of the hormone on cytolytic activity. Histamine was found to inhibit cytolysis reversibly and to increase lymphoid cell cyclic AMP levels. Both of these histamine activities were reversed by burimamide and metiamide; neither activity was affected by diphenhydramine or pyrilamine. These findings indicate that modulation of effector T cell activity by histamine is mediated only by one of the subtypes of tissue histamine receptors, designated a histamine-type 2 receptor. This receptor appears to be present on cytolytically active cells; there is no evidence for activation by histamine of auxiliary or \"suppressor\" cells. The estimated dissociation constant (KB) for the burimamide-receptor complex (9 times 10-minus 6 tm) and for the metiamide-receptor complex (8 times 10-minus 7 M) indicated that the histamine receptor on T cells is quite similar to histamine-type 2 receptors in other tissues. Cells bearing such receptors could not be isolated by passage through a column of histamine-coated tsepharose beads. The cytolytic activity of spleen cells taken from mice early (days 7-9) after immunization is virtually unaffected by histamine in vitro. In contrast, the activity of spleen cells taken from mice later in the immune response is progressively more susceptible to inhibition by histamine. After reaching a maximum at day 11, the spleen cell cytolytic activity falls in a pattern that parallels the increase in susceptibility to histamine. The susceptibility of effector T cells to histamine appears also to reflect their site of origin, for peritoneal exudate effector cells were found to be significantly less sensitive than spleen cells to inhibition by histamine. The progressive increase in inhibition by histamine apparently reflects the appearance of greater numbers of specific histamine-type 2 receptors, and is probably a general phenomenon, for spleen cells from A/J or C3H mice immunized with either P815 mastocytoma (H-2d) or EL-4 (H-2b) cells showed the same effect. However, the appearance of histamine receptors could be altered by prior immunization with an unrelated alloantigen: thus, when A/J mice are preimmunized with EL-4, a subsequent immunization with mastocytoma cells results in peak spleen anti-H-2d activity at day 9 instead of days 11-13, and the appearance of significant (greater than 40 percent) inhibition by histamine as early as day 8 instead of day 16. The physiological role of the histamine receptors is as yet undefined, though their unexpected rate of appearance on effector T cells, coincident with a decline in the number of lytically active cells in vivo, may be a significant hint that hormone receptors play a role in the control of T-cell proliferation."} {"id": "PMID:164484", "title": "Nature of the vagal inhibitory innervation to the lower esophageal sphincter.", "content": "The purpose of the present study was to investigate the nature of the vagal inhibitory innervation to the lower esophageal sphincter in the anesthetized opossum. Sphincter relaxation with electrical stimulation of the vagus was not antagonized by atropine, propranolol, phentolamine, or by catechloamine depletion with reserpine. A combination of atropine and propranolol was also ineffective, suggesting that the vagal inhibitory influences may be mediated by the noncholinergic, nonadrenergic neurons. To determine whether a synaptic link with nicotinic transmission was present, we investigated the effect of hexamethonium on vagal-stimulated lower esophageal sphincter relaxation. Hexamethonium in doses that completely antagonized the sphincter relaxation in response to a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), did not block the sphincter relaxation in response to vagal stimulation at 10 pulses per second, and optimal frequency of stimulation. A combination of hexamethonium and catecholamine depletion was also ineffective, but hexamethonium plus atropine markedly antagonized sphincter relaxation (P less than 0.001). Moreover, 4-(m-chlorophenyl carbamoyloxy)-2-butyltrimethylammonium chloride (McN-A-343), a muscarinic ganglionic stimulant, also caused relaxation of the lower esophageal sphincter. We suggest from these results that: (a) pthe vagal inhibitory pathway to the sphincter consists of preganglionic fibers which synapse with postganglionic neurons: (b) the synaptic transmission is predominantly cholinergic and utilizes nicotinic as well as muscarinic receptors on the postganglionic neuron, and; (c) postganglionic neurons exert their influence on the sphincter by an unidentified inhibitory transmitter that is neither adrenergic nor cholinergic.", "contents": "Nature of the vagal inhibitory innervation to the lower esophageal sphincter. The purpose of the present study was to investigate the nature of the vagal inhibitory innervation to the lower esophageal sphincter in the anesthetized opossum. Sphincter relaxation with electrical stimulation of the vagus was not antagonized by atropine, propranolol, phentolamine, or by catechloamine depletion with reserpine. A combination of atropine and propranolol was also ineffective, suggesting that the vagal inhibitory influences may be mediated by the noncholinergic, nonadrenergic neurons. To determine whether a synaptic link with nicotinic transmission was present, we investigated the effect of hexamethonium on vagal-stimulated lower esophageal sphincter relaxation. Hexamethonium in doses that completely antagonized the sphincter relaxation in response to a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), did not block the sphincter relaxation in response to vagal stimulation at 10 pulses per second, and optimal frequency of stimulation. A combination of hexamethonium and catecholamine depletion was also ineffective, but hexamethonium plus atropine markedly antagonized sphincter relaxation (P less than 0.001). Moreover, 4-(m-chlorophenyl carbamoyloxy)-2-butyltrimethylammonium chloride (McN-A-343), a muscarinic ganglionic stimulant, also caused relaxation of the lower esophageal sphincter. We suggest from these results that: (a) pthe vagal inhibitory pathway to the sphincter consists of preganglionic fibers which synapse with postganglionic neurons: (b) the synaptic transmission is predominantly cholinergic and utilizes nicotinic as well as muscarinic receptors on the postganglionic neuron, and; (c) postganglionic neurons exert their influence on the sphincter by an unidentified inhibitory transmitter that is neither adrenergic nor cholinergic."} {"id": "PMID:164485", "title": "Bronchorrhoea in a case of alveolar cell carcinoma.", "content": "In a case of bronchorrhoea associated with alveolar cell carcinoma thf rheological and chemical features of the sputum indicated that it was bronchial fluid and not saliva and part bronchial secretion, partly serum transudate. The viscosity and chemical constituents were similar to those found in bronchorrhoea when associated with chronic bronchitis, asthma, or bronchiectasis. The surfactant studies suggested an alveolar origin for most of thf fluid, while the failure of fluid restriction, corticosteroids, atropine, or cytotoxic drugs to influence the sputum volume and properties indicated that the cells responsible are \"autonomous\".", "contents": "Bronchorrhoea in a case of alveolar cell carcinoma. In a case of bronchorrhoea associated with alveolar cell carcinoma thf rheological and chemical features of the sputum indicated that it was bronchial fluid and not saliva and part bronchial secretion, partly serum transudate. The viscosity and chemical constituents were similar to those found in bronchorrhoea when associated with chronic bronchitis, asthma, or bronchiectasis. The surfactant studies suggested an alveolar origin for most of thf fluid, while the failure of fluid restriction, corticosteroids, atropine, or cytotoxic drugs to influence the sputum volume and properties indicated that the cells responsible are \"autonomous\"."} {"id": "PMID:164487", "title": "Role of pituitary-adrenocortical system in mediating avoidance behavior of rats with septal lesions.", "content": "Three experiments examined the hypothesis that the effects of septal lesions and systemic injections of scopolamine on avoidance acquisition could be attributed to the effects of either of these treatments on adrenocorticotropic hormone (ACTH) secretion. Septal lesions and scopolamine facilitated 2-way conditioned avoidance response acquisition, and the lesions retarded passive avoidance acquisition. However, neither the injections of dexamethasone, a synthetic glucocorticoid which inhibited ACTH secretion as did septal lesions, nor injections of ACTH which mimicked the facilitatory effects of scopolamine on basal ACTH secretion, affected avoidance in these paradigms. Thus, the main hypothesis was not supported. The finding that scopolamine did not affect passive avoidance indicates that a cholinergic system may not be involved in mediating the suppressive effects of punishment.", "contents": "Role of pituitary-adrenocortical system in mediating avoidance behavior of rats with septal lesions. Three experiments examined the hypothesis that the effects of septal lesions and systemic injections of scopolamine on avoidance acquisition could be attributed to the effects of either of these treatments on adrenocorticotropic hormone (ACTH) secretion. Septal lesions and scopolamine facilitated 2-way conditioned avoidance response acquisition, and the lesions retarded passive avoidance acquisition. However, neither the injections of dexamethasone, a synthetic glucocorticoid which inhibited ACTH secretion as did septal lesions, nor injections of ACTH which mimicked the facilitatory effects of scopolamine on basal ACTH secretion, affected avoidance in these paradigms. Thus, the main hypothesis was not supported. The finding that scopolamine did not affect passive avoidance indicates that a cholinergic system may not be involved in mediating the suppressive effects of punishment."} {"id": "PMID:164488", "title": "Effect of adrenocorticotropic hormone on conditioned avoidance in rats interpreted as state-dependent learning.", "content": "Rats were given one training trial that was followed 2 days later by one test trial in a \"step-out\" passive avoidance task. Each rat was injected with either adrenocorticotropic hormone (ACTH) or placebo before training and before testing. Four groups of rats were used, representing the 4 possible training-testing injection combinations: placebo-placebo, placebo-ACTH, ACTH-placebo, and ACTH-ACTH. ACTH given in testing increased avoidance for subjects that had received ACTH in training and decreased avoidance for those that had received placebo in training.", "contents": "Effect of adrenocorticotropic hormone on conditioned avoidance in rats interpreted as state-dependent learning. Rats were given one training trial that was followed 2 days later by one test trial in a \"step-out\" passive avoidance task. Each rat was injected with either adrenocorticotropic hormone (ACTH) or placebo before training and before testing. Four groups of rats were used, representing the 4 possible training-testing injection combinations: placebo-placebo, placebo-ACTH, ACTH-placebo, and ACTH-ACTH. ACTH given in testing increased avoidance for subjects that had received ACTH in training and decreased avoidance for those that had received placebo in training."} {"id": "PMID:164490", "title": "Subsensitivity to epinephrine following the administration of epinephrine and ephedrine to normal individuals.", "content": "Cardiovascular and metabolic responses to exercise and consecutive epinephrine infusions 24 hours apart were measured in 7 normal individuals before and following a week's administration of ephedrine sulfate. There was evidence of less beta adrenergic response to the second control epinephrine infusion compared to the first control infusion, and the depression of the rise in blood lactate was significantly different. A week of ephedrine produced more profound depression of the beta adrenergic responses to epinephrine with significant differences in the rise in blood glucose and lactate, and the pulse and blood pressure responses. Furthermore, these same responses remained significantly altered when a second epinephrine infusion was performed 36 hours following the last dose of ephedrine. The alterations in the response to epinephrine induced by ephedrine are consistent with the concept of effector cell \"subsensitivity,\" an adaptive response to prolonged excessive stimulation.", "contents": "Subsensitivity to epinephrine following the administration of epinephrine and ephedrine to normal individuals. Cardiovascular and metabolic responses to exercise and consecutive epinephrine infusions 24 hours apart were measured in 7 normal individuals before and following a week's administration of ephedrine sulfate. There was evidence of less beta adrenergic response to the second control epinephrine infusion compared to the first control infusion, and the depression of the rise in blood lactate was significantly different. A week of ephedrine produced more profound depression of the beta adrenergic responses to epinephrine with significant differences in the rise in blood glucose and lactate, and the pulse and blood pressure responses. Furthermore, these same responses remained significantly altered when a second epinephrine infusion was performed 36 hours following the last dose of ephedrine. The alterations in the response to epinephrine induced by ephedrine are consistent with the concept of effector cell \"subsensitivity,\" an adaptive response to prolonged excessive stimulation."} {"id": "PMID:164491", "title": "Leukocytic epinephrine receptors of normal and asthmatic individuals.", "content": "To determine if the hypothesized beta adrenergic blockade in asthma is located at the level of the hormone receptor, we have compared the number and binding affinity of leukocytic epinephrine receptors in normal and asthmatic subjects. Human leukocytes, but not human erythrocytes, possess low-affinity epinephrine receptors. When saturated, each leukocyte binds approximately 1.0 times 10-6 molecules of epinephrine. Binding of 3H DL-epinephrine was largely inhibited by excess unlabeled L-epinephrine. The binding was reversible and involved both the D and L forms of 3H DL-epinephrine. Inhibition studies with nonradioactive isoproterenol, norepinephrine, propranolol, and tolazoline produced results consistent with the interpretation that the leukocytes contained both alpha and beta adrenergic receptors. Two procedures, subcellular fractionation of lymphocytes and incubation of leukocytes in 0.1 per cent trypsin, permitted the demonstration that most of the catecholamine binding occurred at the plasma membrane. Thin-layer chromatography of the bound 3H DL-epinephrine after its extraction from the leukocytes permitted the interpretation that the hormone had fully retained its chemical structure. In addition, epinephrine binding was associated with cAMP production. Leukocytic epinephrine receptors of 10 asthmatic and 9 normal individuals were compared and found not to be substantially different in number or binding affinity.", "contents": "Leukocytic epinephrine receptors of normal and asthmatic individuals. To determine if the hypothesized beta adrenergic blockade in asthma is located at the level of the hormone receptor, we have compared the number and binding affinity of leukocytic epinephrine receptors in normal and asthmatic subjects. Human leukocytes, but not human erythrocytes, possess low-affinity epinephrine receptors. When saturated, each leukocyte binds approximately 1.0 times 10-6 molecules of epinephrine. Binding of 3H DL-epinephrine was largely inhibited by excess unlabeled L-epinephrine. The binding was reversible and involved both the D and L forms of 3H DL-epinephrine. Inhibition studies with nonradioactive isoproterenol, norepinephrine, propranolol, and tolazoline produced results consistent with the interpretation that the leukocytes contained both alpha and beta adrenergic receptors. Two procedures, subcellular fractionation of lymphocytes and incubation of leukocytes in 0.1 per cent trypsin, permitted the demonstration that most of the catecholamine binding occurred at the plasma membrane. Thin-layer chromatography of the bound 3H DL-epinephrine after its extraction from the leukocytes permitted the interpretation that the hormone had fully retained its chemical structure. In addition, epinephrine binding was associated with cAMP production. Leukocytic epinephrine receptors of 10 asthmatic and 9 normal individuals were compared and found not to be substantially different in number or binding affinity."} {"id": "PMID:164497", "title": "Age related activity changes in arginine phosphokinase in the house fly, Musca domestic+ L.", "content": "The activity of ATP; L-arginine phosphotransferase (E.C.2.7.3.3.), was shown to exhibit age-dependent changes in both male and female house fly. Enzyme activity demonstrated more marked changes in the male than in the female, increasing 44-fold from emergence to a peak at 2 days of age and thereafter declining, at first sharply then gradually to a value at 14 days of age, representing a third of the activity found at the peak. Activity in the female fly also showed a peak at 2 days of age, which thereafter declined, although more gradually than was observed in the male. Activity changes expressed on a per fly or wet weight bases were nearly identical. Age-related activity changes on a milligram protein basis demonstrated similar increases; however, the percentage decrease from the 2-day peaks were less striking, although highly significant. No kinetic or physical changes in the enzyme were detected, nor could any soluble inhibitors or activators of enzyme be identified. The changes in arginine phosphokinase activity fall into a sequential pattern of enzyme changes, reflecting an apparently ordered mechanism underlying a decline in flight ability in this species.", "contents": "Age related activity changes in arginine phosphokinase in the house fly, Musca domestic+ L. The activity of ATP; L-arginine phosphotransferase (E.C.2.7.3.3.), was shown to exhibit age-dependent changes in both male and female house fly. Enzyme activity demonstrated more marked changes in the male than in the female, increasing 44-fold from emergence to a peak at 2 days of age and thereafter declining, at first sharply then gradually to a value at 14 days of age, representing a third of the activity found at the peak. Activity in the female fly also showed a peak at 2 days of age, which thereafter declined, although more gradually than was observed in the male. Activity changes expressed on a per fly or wet weight bases were nearly identical. Age-related activity changes on a milligram protein basis demonstrated similar increases; however, the percentage decrease from the 2-day peaks were less striking, although highly significant. No kinetic or physical changes in the enzyme were detected, nor could any soluble inhibitors or activators of enzyme be identified. The changes in arginine phosphokinase activity fall into a sequential pattern of enzyme changes, reflecting an apparently ordered mechanism underlying a decline in flight ability in this species."} {"id": "PMID:164498", "title": "Determination of the glycogen content in single neutrophil leukocytes using a micromodel of leukocyte glycogen.", "content": "The kinetics of the periodic acid oxidation as part of the periodic acid-Schiff reaction was studied by combined microinterferometry and microspectrophotometry in micromodel systems of liver glycogen and leukocyte glycogen as well as in neutrophil leukocytes. The initial formation of Schiff-positive chromogens was more rapid in neutrophil leukocytes than in liver or leukocyte glycogen. The chromogen formation was, however, practically complete within 60 min in both neutrophil leukocytes and leukocyte glycogen, but this did not appear to be the case in liver glycogen. Differences in the rate of chromogen formation may depend on various factors such as differences in the source and treatment of the glycogen. The complete periodic acid-Schiff reaction appears to be a measure of the glycogen amount in neutrophil leukocytes and the microdroplet system of leukocyte glycogen is considered to be an appropriate model for the estimation of the glycogen amount in single neutrophil leukocytes. A mean value of 13.3 10-12 g glycogen per normal human neutrophil was found.", "contents": "Determination of the glycogen content in single neutrophil leukocytes using a micromodel of leukocyte glycogen. The kinetics of the periodic acid oxidation as part of the periodic acid-Schiff reaction was studied by combined microinterferometry and microspectrophotometry in micromodel systems of liver glycogen and leukocyte glycogen as well as in neutrophil leukocytes. The initial formation of Schiff-positive chromogens was more rapid in neutrophil leukocytes than in liver or leukocyte glycogen. The chromogen formation was, however, practically complete within 60 min in both neutrophil leukocytes and leukocyte glycogen, but this did not appear to be the case in liver glycogen. Differences in the rate of chromogen formation may depend on various factors such as differences in the source and treatment of the glycogen. The complete periodic acid-Schiff reaction appears to be a measure of the glycogen amount in neutrophil leukocytes and the microdroplet system of leukocyte glycogen is considered to be an appropriate model for the estimation of the glycogen amount in single neutrophil leukocytes. A mean value of 13.3 10-12 g glycogen per normal human neutrophil was found."} {"id": "PMID:164499", "title": "Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967-1972.", "content": "The role of viruses and M. pneumoniae in episodes of acute respiratory illness in childhood has been studied in a London general practice. The total isolation rate was 31-7 per cent, but the rate varied from 32-6 per cent in upper respiratory infections to 64-0 per cent in pneumonia. The clinical features associated with infection were influenced not only by the type of agent but also by age and other host factors in infected children. Rhinoviruses were more commonly isolated than any other agent and were frequently associated with wheezy bronchitis.", "contents": "Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967-1972. The role of viruses and M. pneumoniae in episodes of acute respiratory illness in childhood has been studied in a London general practice. The total isolation rate was 31-7 per cent, but the rate varied from 32-6 per cent in upper respiratory infections to 64-0 per cent in pneumonia. The clinical features associated with infection were influenced not only by the type of agent but also by age and other host factors in infected children. Rhinoviruses were more commonly isolated than any other agent and were frequently associated with wheezy bronchitis."} {"id": "PMID:164500", "title": "A comparison of some immunological methods for the differentiation of strains of foot-and-mouth disease virus.", "content": "Two FMDV strains which had been previously differentiated by complement-fixation were compared by guinea-pig protection test, kinetic neutralization and micro-neutralization tests. It was found that these tests, which have not been previously applied by the methods described, were all capable of FMDV strain differentiation. Similar differences were found by all methods, which suggests that comparisons made by cross-CF, cross-neutralization or cross-protection involve measurement of the same antigen/antibody interactions.", "contents": "A comparison of some immunological methods for the differentiation of strains of foot-and-mouth disease virus. Two FMDV strains which had been previously differentiated by complement-fixation were compared by guinea-pig protection test, kinetic neutralization and micro-neutralization tests. It was found that these tests, which have not been previously applied by the methods described, were all capable of FMDV strain differentiation. Similar differences were found by all methods, which suggests that comparisons made by cross-CF, cross-neutralization or cross-protection involve measurement of the same antigen/antibody interactions."} {"id": "PMID:164501", "title": "The sub-type classification of strains of foot-and-mouth disease virus.", "content": "Sixteen foot-and-mouth disease virus (FMDV) strains of type SAT 1 were compared in complement-fixation tests. With the test used, the range of antigenic variation within a type appeared to be greater than previously described. The concept of a sub-type group within which all strains are more closely related to each other than to any strain outside the group was not supported. Considering the group of strains studied, it is suggested that the classification of strains is best achieved by moninating a reference strain for each sub-type. Others are classified as related strains in one or more sub-type groups according to their relationships with the reference strains.", "contents": "The sub-type classification of strains of foot-and-mouth disease virus. Sixteen foot-and-mouth disease virus (FMDV) strains of type SAT 1 were compared in complement-fixation tests. With the test used, the range of antigenic variation within a type appeared to be greater than previously described. The concept of a sub-type group within which all strains are more closely related to each other than to any strain outside the group was not supported. Considering the group of strains studied, it is suggested that the classification of strains is best achieved by moninating a reference strain for each sub-type. Others are classified as related strains in one or more sub-type groups according to their relationships with the reference strains."} {"id": "PMID:164502", "title": "Respiratory and humoral immune response to aerosol and intramuscular pertussis vaccine.", "content": "Animal experiments have shown that respiratory administration of pertussis antigen induces a protective immune response. In this study pertussis antibody in human respiratory secretions was measured and the response to aerosol and intramuscular pertussis immunization investigated. Substanial increases in this antibody occurred after aerosol immunization but no changes were found in serum antibody. The reverse was observed after intramuscular pertussis vaccine in adults but not with aerosol immunization. The latter method may be of value for paediatric medical and nursing personnel exposed to the risk of pertussis infection.", "contents": "Respiratory and humoral immune response to aerosol and intramuscular pertussis vaccine. Animal experiments have shown that respiratory administration of pertussis antigen induces a protective immune response. In this study pertussis antibody in human respiratory secretions was measured and the response to aerosol and intramuscular pertussis immunization investigated. Substanial increases in this antibody occurred after aerosol immunization but no changes were found in serum antibody. The reverse was observed after intramuscular pertussis vaccine in adults but not with aerosol immunization. The latter method may be of value for paediatric medical and nursing personnel exposed to the risk of pertussis infection."} {"id": "PMID:164503", "title": "Sero-immunity to poliovirus in children and young women: England 1972-4.", "content": "A total of 292 children's sera and 706 antenatal sera from different parts of England were tested for the presence of poliovirus neutralizing antibodies. Little vairation was found between different areas and types of community, but a lower porportion of the 5-14 year old children had antibody than younger children and young adult women. The proportion of the young population with antibody, and the current acceptance rates for oral poliovirus vaccine are barely satisfactory.", "contents": "Sero-immunity to poliovirus in children and young women: England 1972-4. A total of 292 children's sera and 706 antenatal sera from different parts of England were tested for the presence of poliovirus neutralizing antibodies. Little vairation was found between different areas and types of community, but a lower porportion of the 5-14 year old children had antibody than younger children and young adult women. The proportion of the young population with antibody, and the current acceptance rates for oral poliovirus vaccine are barely satisfactory."} {"id": "PMID:164504", "title": "Specific susceptibility of sensitized (memory) B cells to suppression and antigenic alteration by murine leukemia virus.", "content": "Mice infected with murine oncogenic RNA viruses, either Friend virus (FV) or Moloney leukemia virus (MuLV-M) reacted well to a primary immunization with antigen(s) of Vibrio cholerae; both the kinetics and magnitude of the direct (IgM) primary vibriolytic antibody plaque forming cell (PFC) response in the spleen was the same as in non-infected control mice. In contrast, the anamnestic PFC (IgM) response of mice preimmunized with cholera and later (2 to 9 months following priming) infected with either FV or MuLV-M, before the secondary challenge, was inhibited 90% or more when compared to the anamnestic response of controls. Hemolytic PFC response to a single (primary) immunization with sheep red blood cells (sRBC, an antigen to which laboratory mice have a natural immune background) was suppressed by infection with both viruses in a manner similar to the suppression of the secondary vibiolytic response. The suppressive effect of FV, and the lack of it, on these different immune responses was correlated with the appearance of FV-induced cell membrane antigen, FVMA, on respective individual PFC from the spleen. FVMA was detected by inhibition of PFC in the presence of specific antiserum, anti-FVMA, and complement (C). In particular, about 80% of the FV-infected mice with an anamnestic response to a secondary challenge with cholera antigen had a significant decline in the proportion of PFC (33% or more) following incubation with anti-FVMA plus C. A similar degree of inhibition was found with hemolytic (anti-sRBC) PFC from FV-infected mice. In contrast, primary vibriolytic PFC from FV-infected mice were not inhibited by anti-FVMA, i.e., they did not carry the virus-induced antigen. These results indicate absolute correlation between viral suppression of a given clone of immunocompetent cells, and antigenic alteration of individual antibody-forming cells due to the virus-infection. Furthermore, the absence of both functional inhibition and virus-induced antigen(s) in the primary immunocompetent cells and the presence of both these virus-related functions in the memory cells (either experimentally sensitized cholera memory cells or naturally sensitized sRBC memory cells) strongly suggested that the latter are selectively susceptible to oncornavirus.", "contents": "Specific susceptibility of sensitized (memory) B cells to suppression and antigenic alteration by murine leukemia virus. Mice infected with murine oncogenic RNA viruses, either Friend virus (FV) or Moloney leukemia virus (MuLV-M) reacted well to a primary immunization with antigen(s) of Vibrio cholerae; both the kinetics and magnitude of the direct (IgM) primary vibriolytic antibody plaque forming cell (PFC) response in the spleen was the same as in non-infected control mice. In contrast, the anamnestic PFC (IgM) response of mice preimmunized with cholera and later (2 to 9 months following priming) infected with either FV or MuLV-M, before the secondary challenge, was inhibited 90% or more when compared to the anamnestic response of controls. Hemolytic PFC response to a single (primary) immunization with sheep red blood cells (sRBC, an antigen to which laboratory mice have a natural immune background) was suppressed by infection with both viruses in a manner similar to the suppression of the secondary vibiolytic response. The suppressive effect of FV, and the lack of it, on these different immune responses was correlated with the appearance of FV-induced cell membrane antigen, FVMA, on respective individual PFC from the spleen. FVMA was detected by inhibition of PFC in the presence of specific antiserum, anti-FVMA, and complement (C). In particular, about 80% of the FV-infected mice with an anamnestic response to a secondary challenge with cholera antigen had a significant decline in the proportion of PFC (33% or more) following incubation with anti-FVMA plus C. A similar degree of inhibition was found with hemolytic (anti-sRBC) PFC from FV-infected mice. In contrast, primary vibriolytic PFC from FV-infected mice were not inhibited by anti-FVMA, i.e., they did not carry the virus-induced antigen. These results indicate absolute correlation between viral suppression of a given clone of immunocompetent cells, and antigenic alteration of individual antibody-forming cells due to the virus-infection. Furthermore, the absence of both functional inhibition and virus-induced antigen(s) in the primary immunocompetent cells and the presence of both these virus-related functions in the memory cells (either experimentally sensitized cholera memory cells or naturally sensitized sRBC memory cells) strongly suggested that the latter are selectively susceptible to oncornavirus."} {"id": "PMID:164505", "title": "Lymphocyte depletion induced by cholera toxin; relationship to adrenal cortical function.", "content": "Intravenous injection of cholera toxin (choleragen) into mice caused a profound lymphocytopenia associated with marked cellular depletion of the lymph nodes, spleen, and thymus. After administration of 1 mu g of choleragen, lymphocytopenia was mot marked at 24 hr; recovery occurred 6 to 10 days later. Similarly depletion of lymph nodes and spleen was maximal at 24 hr with recovery by 14 days. Choleragen also caused a marked elevation of serum corticosterone and lymphocyte depletion was not observed in adrenalectomized mice. These results suggested that the lymphocytopenic effect of choleragen was mediated by increased production and secretion of adrenal cortical hormones secondary to a rise in intracellular cAMP induced by cholera toxin. The site of action of choleragen may be the adrenal cortex itself and/or the hypothalamic-pituitary system.", "contents": "Lymphocyte depletion induced by cholera toxin; relationship to adrenal cortical function. Intravenous injection of cholera toxin (choleragen) into mice caused a profound lymphocytopenia associated with marked cellular depletion of the lymph nodes, spleen, and thymus. After administration of 1 mu g of choleragen, lymphocytopenia was mot marked at 24 hr; recovery occurred 6 to 10 days later. Similarly depletion of lymph nodes and spleen was maximal at 24 hr with recovery by 14 days. Choleragen also caused a marked elevation of serum corticosterone and lymphocyte depletion was not observed in adrenalectomized mice. These results suggested that the lymphocytopenic effect of choleragen was mediated by increased production and secretion of adrenal cortical hormones secondary to a rise in intracellular cAMP induced by cholera toxin. The site of action of choleragen may be the adrenal cortex itself and/or the hypothalamic-pituitary system."} {"id": "PMID:164506", "title": "The isolation and characterization of the V-H domain from rabbit heavy chains of different a locus allotype.", "content": "The Fd fragment of rabbit gamma-chains was split by papain to yield a smaller fragment with a molecular weight of approximately 14,000 and dialyzable small peptides and amino acids. The domain size fragment was identified as intact variable region from its amino acid content, its blocked amino-terminus, and two characteristic cysteine-containing peptides, while the small peptides and amino acids were accounted for by the degradation of the C-H1 region. The variable regions isolated from Aa1 and Aa3 Fd fragments not only reacted quantitatively with immunoadsorbents conjugated with the homologous anti-a allotype antibody, but also completely inhibited the binding of the parent Fd fragment to the homologous antibody as measured by radioimmune assay. These data provide direct evidence that the group a allotypic determinants are contained entirely in the variable portion and are independent of the constant portion of rabbit heavy chains.", "contents": "The isolation and characterization of the V-H domain from rabbit heavy chains of different a locus allotype. The Fd fragment of rabbit gamma-chains was split by papain to yield a smaller fragment with a molecular weight of approximately 14,000 and dialyzable small peptides and amino acids. The domain size fragment was identified as intact variable region from its amino acid content, its blocked amino-terminus, and two characteristic cysteine-containing peptides, while the small peptides and amino acids were accounted for by the degradation of the C-H1 region. The variable regions isolated from Aa1 and Aa3 Fd fragments not only reacted quantitatively with immunoadsorbents conjugated with the homologous anti-a allotype antibody, but also completely inhibited the binding of the parent Fd fragment to the homologous antibody as measured by radioimmune assay. These data provide direct evidence that the group a allotypic determinants are contained entirely in the variable portion and are independent of the constant portion of rabbit heavy chains."} {"id": "PMID:164507", "title": "Partial characterization of a soluble antigen preparation from cells infected with human cytomegalovirus: properties of antisera prepared to the antigen.", "content": "Soluble antigen (SA) preparations were obtained from cell cultures infected with either the Davis or AD169 strains of cytomegalovirus (CMV). Fractionation of SA preparations through Sephadex G-200 resulted in a molecular weight value ranging from 67,000 to 85,000. Rate-zonal centrifugation produced an approximate value of 5.5S for the CMV antigenic material. Antisera to SA prepared from either AD169- or Davis-infected cells lacked neutralizing activity but produced specific fluorescence confined to CMV intranuclear inclusion material when used in the indirect fluorescent antibody test (IFA). The specific fluorescing inclusion reaction was seen when either AD169 or Davis antisera were used with cells infected with the Davis, AD169, Kerr, or C-87 strains of CMV. Fluorescence was not observed in cells infected with a strain of Herpes simplex type 1, varicella-zoster virus, an EBV transformed lymphocyte line, the Cx-90-3B human CMV transformed hamster embryo cell line or CMV-infected cell cultures treated with cytosine arabinoside (Ara-C) and showing only antigens expressed in the absence of viral DNA synthesis. Antisera prepared to SA preparations obtained from CMV-infected cells apparently react with specific CMV antigens that are dependent on viral DNA synthesis and are common to several strains.", "contents": "Partial characterization of a soluble antigen preparation from cells infected with human cytomegalovirus: properties of antisera prepared to the antigen. Soluble antigen (SA) preparations were obtained from cell cultures infected with either the Davis or AD169 strains of cytomegalovirus (CMV). Fractionation of SA preparations through Sephadex G-200 resulted in a molecular weight value ranging from 67,000 to 85,000. Rate-zonal centrifugation produced an approximate value of 5.5S for the CMV antigenic material. Antisera to SA prepared from either AD169- or Davis-infected cells lacked neutralizing activity but produced specific fluorescence confined to CMV intranuclear inclusion material when used in the indirect fluorescent antibody test (IFA). The specific fluorescing inclusion reaction was seen when either AD169 or Davis antisera were used with cells infected with the Davis, AD169, Kerr, or C-87 strains of CMV. Fluorescence was not observed in cells infected with a strain of Herpes simplex type 1, varicella-zoster virus, an EBV transformed lymphocyte line, the Cx-90-3B human CMV transformed hamster embryo cell line or CMV-infected cell cultures treated with cytosine arabinoside (Ara-C) and showing only antigens expressed in the absence of viral DNA synthesis. Antisera prepared to SA preparations obtained from CMV-infected cells apparently react with specific CMV antigens that are dependent on viral DNA synthesis and are common to several strains."} {"id": "PMID:164508", "title": "Distinction between malignant L cells and normal mouse fibroblasts by rosette formation with sheep red blood cells.", "content": "Murine L cell fibroblasts, and derivatives were found to rosette with sheep red blood cells (SRBC). Primary fibroblast explants from the parent murine strain, C3H, did not possess this potential. No rosettes were observed with primary fibroblast explants from C57BL and B10Br mice, with a human fetal lung fibroblast, with baby hamster fibroblasts or their polyoma transormed derivative, or with a cell line, 1T-22, derived from BALB/c mice. Hybridization of 1T-22 and L cells, by Sendai virus-mediated cell fusion, suppressed the rosette potential of the L cell parent. The receptor for SRBC on L cells appears to result from the expression of a recessive characteristic.", "contents": "Distinction between malignant L cells and normal mouse fibroblasts by rosette formation with sheep red blood cells. Murine L cell fibroblasts, and derivatives were found to rosette with sheep red blood cells (SRBC). Primary fibroblast explants from the parent murine strain, C3H, did not possess this potential. No rosettes were observed with primary fibroblast explants from C57BL and B10Br mice, with a human fetal lung fibroblast, with baby hamster fibroblasts or their polyoma transormed derivative, or with a cell line, 1T-22, derived from BALB/c mice. Hybridization of 1T-22 and L cells, by Sendai virus-mediated cell fusion, suppressed the rosette potential of the L cell parent. The receptor for SRBC on L cells appears to result from the expression of a recessive characteristic."} {"id": "PMID:164509", "title": "Mastocytoma cell migration in vitro: inhibition by MIF-containing supernatants.", "content": "Supernatants with macrophage migration inhibition factor (MIF) activity were obtained from cultures of antigen-stimulated guinea pig and human lymphocytes, and from SV40-infected monkey kidney cells. The monkey and human but not guinea pig preparations were effective in inhibiting migration of mastocytoma cells as well as macrophages. This inhibition of migration was not associated with cytotoxicity and was reversible.", "contents": "Mastocytoma cell migration in vitro: inhibition by MIF-containing supernatants. Supernatants with macrophage migration inhibition factor (MIF) activity were obtained from cultures of antigen-stimulated guinea pig and human lymphocytes, and from SV40-infected monkey kidney cells. The monkey and human but not guinea pig preparations were effective in inhibiting migration of mastocytoma cells as well as macrophages. This inhibition of migration was not associated with cytotoxicity and was reversible."} {"id": "PMID:164510", "title": "Papaverine: its effects on cyclic AMP in vitro and psoriasis in vivo.", "content": "Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 x 10-4 m) produced a 210percent increase (.02 smaller than p smaller than .05) in epidermal cyclic AMP levels in vitro. Therefore, 1 percent papaverine cream (approximately 2.7 x 10-2m papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a soriatic lesion. A double-blind comparison of 1 percent papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81 percent (p=0.011) of those showing a response in the center of the lesion and 77 percent (p=0.046) of those improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments.", "contents": "Papaverine: its effects on cyclic AMP in vitro and psoriasis in vivo. Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 x 10-4 m) produced a 210percent increase (.02 smaller than p smaller than .05) in epidermal cyclic AMP levels in vitro. Therefore, 1 percent papaverine cream (approximately 2.7 x 10-2m papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a soriatic lesion. A double-blind comparison of 1 percent papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81 percent (p=0.011) of those showing a response in the center of the lesion and 77 percent (p=0.046) of those improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments."} {"id": "PMID:164511", "title": "The genetic relationship of abetalipoproteinemia and hypobetalipoproteinemia: a report of the occurence of both diseases within the same family.", "content": "A new case of abetalipoproteinemia (ABL) is reported after its recognition during an acquired hemorrhagic disthesis at parturition in a 37-year-old female. The new born infant of that delivery and 4 other first-degree relatives were subsequently studied and found to have hypobetalipoproteinemia (HBL). ABL and HBL, while sharing many clinical and biochemical similarities have, but rarely, been demonstrated within the same kindred and have, therefore, been regarded as different genetic mutations. Analysis of the data in the present and two other reported families indicates that ABL can result from the homozygous inheritance of the same gene which, when present in the heterozygous state, results in HBL't is concluded, therefore, that these cases of ABL have apparently been inherited via a different genetic mutation than most previously reported cases of ABL,and is likely the same gene involved in HBL. The clinical presentation of this form of ABL, that is, familial homozygous hypobetalipoproteinemia, is compared to that of the classical form of ABL.", "contents": "The genetic relationship of abetalipoproteinemia and hypobetalipoproteinemia: a report of the occurence of both diseases within the same family. A new case of abetalipoproteinemia (ABL) is reported after its recognition during an acquired hemorrhagic disthesis at parturition in a 37-year-old female. The new born infant of that delivery and 4 other first-degree relatives were subsequently studied and found to have hypobetalipoproteinemia (HBL). ABL and HBL, while sharing many clinical and biochemical similarities have, but rarely, been demonstrated within the same kindred and have, therefore, been regarded as different genetic mutations. Analysis of the data in the present and two other reported families indicates that ABL can result from the homozygous inheritance of the same gene which, when present in the heterozygous state, results in HBL't is concluded, therefore, that these cases of ABL have apparently been inherited via a different genetic mutation than most previously reported cases of ABL,and is likely the same gene involved in HBL. The clinical presentation of this form of ABL, that is, familial homozygous hypobetalipoproteinemia, is compared to that of the classical form of ABL."} {"id": "PMID:164512", "title": "Studies on gel-filtered human platelets: isolation and characterization in a medium containing no added Ca2+, Mg2+, or K+.", "content": "We have adapted the gel filtration technique for separation of human platelets from the plasma constituents to permit use of an eluant containing no added Ca2+, Mg2+, and K+, and hence allow direct determination of the intracellular concentrations of these ions in the isolated platelets. The eluant employed is modified Ca2+-free Tyrode's buffer which contains Sr2+ (0.2 mM) as a substitute for Mg2+ and lacks added K+. The functional metabolic, and morphological properties of these isolated platelets have been determined ael-filtered platelets (GFP) to low concentrations of ADP and adrenaline was qualitatively similar to that of platelet-rich plasma (PRP). However, a slower response was observed for the GFP. This rate difference was partially or completely reversed by addition of apyrase to the medium. Analysis of the total adenine nucleotide content and the pattern of 14C incorporation into the metabolic adenine nucleotide pool indicated that isolation in this medium caused to significant change in the ATP and ADP contents or in the adenylate energy change in comparison with the PRP. However, a significant increase in the extent of hypoxanthine production from ATP was noted in GFP isolated in media lacking Mg2+. Inclusion of Mg2+ in the elution media prevented this increased hypoxanthine production. The intracellular concentrations of Ca2+, Mg2+, and K+ of the GFP as determined by atomic absorption analysis were in good agreement with the values obtained for platelets separated from plasma by high-speed centrifugation. Platelet Ca2+ and Mg2+ levels remained stable despite the lack of significant extracellular levels of these ions. However platelet K+ fell to about 30 per cent of its initial value after incubation of 90 minutes at 23 degrees C. and a coincident increase was observed in extracellular K+ concentration. This procedure for platelet isolation may be of particular value for studies on the role of Ca2+, Mg2+, and K+ in platelet physiology and metabolic processes.", "contents": "Studies on gel-filtered human platelets: isolation and characterization in a medium containing no added Ca2+, Mg2+, or K+. We have adapted the gel filtration technique for separation of human platelets from the plasma constituents to permit use of an eluant containing no added Ca2+, Mg2+, and K+, and hence allow direct determination of the intracellular concentrations of these ions in the isolated platelets. The eluant employed is modified Ca2+-free Tyrode's buffer which contains Sr2+ (0.2 mM) as a substitute for Mg2+ and lacks added K+. The functional metabolic, and morphological properties of these isolated platelets have been determined ael-filtered platelets (GFP) to low concentrations of ADP and adrenaline was qualitatively similar to that of platelet-rich plasma (PRP). However, a slower response was observed for the GFP. This rate difference was partially or completely reversed by addition of apyrase to the medium. Analysis of the total adenine nucleotide content and the pattern of 14C incorporation into the metabolic adenine nucleotide pool indicated that isolation in this medium caused to significant change in the ATP and ADP contents or in the adenylate energy change in comparison with the PRP. However, a significant increase in the extent of hypoxanthine production from ATP was noted in GFP isolated in media lacking Mg2+. Inclusion of Mg2+ in the elution media prevented this increased hypoxanthine production. The intracellular concentrations of Ca2+, Mg2+, and K+ of the GFP as determined by atomic absorption analysis were in good agreement with the values obtained for platelets separated from plasma by high-speed centrifugation. Platelet Ca2+ and Mg2+ levels remained stable despite the lack of significant extracellular levels of these ions. However platelet K+ fell to about 30 per cent of its initial value after incubation of 90 minutes at 23 degrees C. and a coincident increase was observed in extracellular K+ concentration. This procedure for platelet isolation may be of particular value for studies on the role of Ca2+, Mg2+, and K+ in platelet physiology and metabolic processes."} {"id": "PMID:164513", "title": "X-ray powder diffraction data for some drugs, excipients, and adulterants in illicit samples.", "content": "X-ray powder diffraction data have been developed or refined for the identification of drugs, excipients, and adulterants found in illicit preparations.", "contents": "X-ray powder diffraction data for some drugs, excipients, and adulterants in illicit samples. X-ray powder diffraction data have been developed or refined for the identification of drugs, excipients, and adulterants found in illicit preparations."} {"id": "PMID:164514", "title": "Proteins of Kirsten murine leukaemia-sarcoma virus: localization within the virus particle by iodination and fractionation techniques.", "content": "The protein and glycoprotein composition of Kirsten murine leukaemia-sarcoma virus (KiMSV(KiMuLV) was studied using SDS-polyacrylamide gel electrophoresis. Twenty-three polypeptides and three glycoproteins were detected following electrophoresis by staining with Coomassie blue and PAS or by autoradiography of isotopically labelled virus. Protein components were assigned positions in the virus particle, envelope, nucleoid or intermediate area based on iodination with lactoperoxidase and sedimentation in potassium citrate equilibrium gradients. The KiMSV (KiMuLV) envelope contained 11 polypeptides and three glycoproteins. The virus nucleoid and intermediate area were each composed of six proteins. The protein composition of KiMSV(KiMuLV) was highly reproducible when virus was harvested from cells of the same subcluture generation. However, the protein profiles were altered with repeated in vitro passages of the virus-producing cell line.", "contents": "Proteins of Kirsten murine leukaemia-sarcoma virus: localization within the virus particle by iodination and fractionation techniques. The protein and glycoprotein composition of Kirsten murine leukaemia-sarcoma virus (KiMSV(KiMuLV) was studied using SDS-polyacrylamide gel electrophoresis. Twenty-three polypeptides and three glycoproteins were detected following electrophoresis by staining with Coomassie blue and PAS or by autoradiography of isotopically labelled virus. Protein components were assigned positions in the virus particle, envelope, nucleoid or intermediate area based on iodination with lactoperoxidase and sedimentation in potassium citrate equilibrium gradients. The KiMSV (KiMuLV) envelope contained 11 polypeptides and three glycoproteins. The virus nucleoid and intermediate area were each composed of six proteins. The protein composition of KiMSV(KiMuLV) was highly reproducible when virus was harvested from cells of the same subcluture generation. However, the protein profiles were altered with repeated in vitro passages of the virus-producing cell line."} {"id": "PMID:164515", "title": "Proteins induced in BHK cells by infection with foot-and-mouth desease virus.", "content": "Although the infection of BHK cells with foot-and-mouth disease virus did not cause a marked inhibition of cellular protein synthesis, the proteins synthesized gradually changed from host-specific to virus-specific. The synthesis of at least thirteen virus-induced proteins was demonstrated by polyacrylamide electrophoretic analysis of the infected cells. Only a small proportion of the virus-induced proteins was incorporated into the mature virus particles. The addition of amino acid analogues caused an accumulation of the larger mol. wt. proteins, suggesting that in infected cells, some cleavages occurred, giving rise to the smaller mol. wt. proteins. The operation of the precursor-cleavage mechanism was more clearly shown in pulse-chase experiments, in which it was found that the proteins were degraded from larger to smaller mol. wt.", "contents": "Proteins induced in BHK cells by infection with foot-and-mouth desease virus. Although the infection of BHK cells with foot-and-mouth disease virus did not cause a marked inhibition of cellular protein synthesis, the proteins synthesized gradually changed from host-specific to virus-specific. The synthesis of at least thirteen virus-induced proteins was demonstrated by polyacrylamide electrophoretic analysis of the infected cells. Only a small proportion of the virus-induced proteins was incorporated into the mature virus particles. The addition of amino acid analogues caused an accumulation of the larger mol. wt. proteins, suggesting that in infected cells, some cleavages occurred, giving rise to the smaller mol. wt. proteins. The operation of the precursor-cleavage mechanism was more clearly shown in pulse-chase experiments, in which it was found that the proteins were degraded from larger to smaller mol. wt."} {"id": "PMID:164516", "title": "Determination of the molecular weight of bovine enterovirus RNA by nuclease digestion.", "content": "The mol. wt. of a [32P]-labelled bovine enterovirus RNA has been determined by digesting with pancreatic RNase and separating the resulting oligonucleotides using a two-stage fractionation method on DEAE-Sephadex in 7 M-urea at pH 7-6 and pH 3-0. We have estimated the number of nucleotides as 8612 plus or minus 55. This corresponds to a mol. wt. of 2-93 plus or minus 0-02 X 10-6 which is in aggrement with estimates obtained by sedimentation and gel electrophoresis techniques.", "contents": "Determination of the molecular weight of bovine enterovirus RNA by nuclease digestion. The mol. wt. of a [32P]-labelled bovine enterovirus RNA has been determined by digesting with pancreatic RNase and separating the resulting oligonucleotides using a two-stage fractionation method on DEAE-Sephadex in 7 M-urea at pH 7-6 and pH 3-0. We have estimated the number of nucleotides as 8612 plus or minus 55. This corresponds to a mol. wt. of 2-93 plus or minus 0-02 X 10-6 which is in aggrement with estimates obtained by sedimentation and gel electrophoresis techniques."} {"id": "PMID:164517", "title": "The pathogenesis of pseudorabies in mice: virus replication at the inoculation site and axonal uptake.", "content": "Three-week-old mice were inoculated in the right ear pinna with pseuforabies virus. Ears were surgically removed at various times after inoculation and changes from the normal pathogenesis were observed. Virus replication in the ear tissue and cervical dorsal root ganglia was also monitored. Followed inoculation with a small dose of virus, local multiplication of the virus was necessary before the infection spread to the nerves. With larger infecting doses there was probably direct uptake of virus from the inoculum into the nerve endings. After these larger doses virus was first detected in the dorsal root ganglia 17 h agter infection, suggesting a retrograde axonal flow rate of at lease 1-7 mm/h.", "contents": "The pathogenesis of pseudorabies in mice: virus replication at the inoculation site and axonal uptake. Three-week-old mice were inoculated in the right ear pinna with pseuforabies virus. Ears were surgically removed at various times after inoculation and changes from the normal pathogenesis were observed. Virus replication in the ear tissue and cervical dorsal root ganglia was also monitored. Followed inoculation with a small dose of virus, local multiplication of the virus was necessary before the infection spread to the nerves. With larger infecting doses there was probably direct uptake of virus from the inoculum into the nerve endings. After these larger doses virus was first detected in the dorsal root ganglia 17 h agter infection, suggesting a retrograde axonal flow rate of at lease 1-7 mm/h."} {"id": "PMID:164518", "title": "Virus DNA synthesizing ability of T antigen-forming defective SV40 produced by successive undiluted passages.", "content": "SV40 stocks prepared by successive undiluted passages in African green monkey kidney (gmk) cells contain particles which produce T antigen but not capsid antigen (T partcles). The DNA of the T particles was shown to replicate during abortive infection of GMK cells, as indicated by immunofluorescence assay for antigen forming capacity of virus DNA. It was also shown that the synthesis of t particle DNA was induced in heterokaryons formed by fusion of 3T3 cells transformed by T particles with susceptible GMK cells.", "contents": "Virus DNA synthesizing ability of T antigen-forming defective SV40 produced by successive undiluted passages. SV40 stocks prepared by successive undiluted passages in African green monkey kidney (gmk) cells contain particles which produce T antigen but not capsid antigen (T partcles). The DNA of the T particles was shown to replicate during abortive infection of GMK cells, as indicated by immunofluorescence assay for antigen forming capacity of virus DNA. It was also shown that the synthesis of t particle DNA was induced in heterokaryons formed by fusion of 3T3 cells transformed by T particles with susceptible GMK cells."} {"id": "PMID:164519", "title": "Unidirectional replication of a minority of polyoma virus and SV40 DNAs.", "content": "Poyoma DNA replication is initiated predominatly at a site which is 29% from the EcoRI cleavage site. Molecules replicating from this site, after digestion with EcoRI appear as linear structures with a double stranded loop centered at the origin of replication. These forms constitute 90% of all replicating intermediates. Approx. 10% of the replicating intermediates of polyoma and SVP40 DNAs occur as Y-forms after treatment with EcoRI. These structures have probably resulted from unidirectional replication initiated at an additional origin of DNA replication which is located near the EcoRI cleavage site on the genomes of these viruses.", "contents": "Unidirectional replication of a minority of polyoma virus and SV40 DNAs. Poyoma DNA replication is initiated predominatly at a site which is 29% from the EcoRI cleavage site. Molecules replicating from this site, after digestion with EcoRI appear as linear structures with a double stranded loop centered at the origin of replication. These forms constitute 90% of all replicating intermediates. Approx. 10% of the replicating intermediates of polyoma and SVP40 DNAs occur as Y-forms after treatment with EcoRI. These structures have probably resulted from unidirectional replication initiated at an additional origin of DNA replication which is located near the EcoRI cleavage site on the genomes of these viruses."} {"id": "PMID:164520", "title": "Isolation and characterization of 'dense particles' from poliovirus-infected HeLa cells.", "content": "Dense poliovirus particles (buoyant density 1.44 g/ml in CsCl) isolated from infected HeLa cells contain the normal four structural polypeptides VP1 to VP4, and 35S poliovirus RNA. In addition, small amounts of VPo and single-stranded RNA sedimenting slower than the poliovirus genome are present. Dense particles have a low specific infectivity, are neutralized by type-specific poliovirus antisera, and are detected during growth as early as normal virus but disappear when virus production stops. They appear to represent a different, more open, conformation of the normal virus capsid.", "contents": "Isolation and characterization of 'dense particles' from poliovirus-infected HeLa cells. Dense poliovirus particles (buoyant density 1.44 g/ml in CsCl) isolated from infected HeLa cells contain the normal four structural polypeptides VP1 to VP4, and 35S poliovirus RNA. In addition, small amounts of VPo and single-stranded RNA sedimenting slower than the poliovirus genome are present. Dense particles have a low specific infectivity, are neutralized by type-specific poliovirus antisera, and are detected during growth as early as normal virus but disappear when virus production stops. They appear to represent a different, more open, conformation of the normal virus capsid."} {"id": "PMID:164521", "title": "Distinct molecular species of human interferons: requirements for stabilzation and reactivation of human leukocyte and fibroblast interferons.", "content": "Human fibroblast interferon preparations were completely stabilized to 100 degrees C by sodium dodecyl sulphate (SDS) in the presence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS without mercaptoethanol. On the contarary, human leukocyte interferon preparations were completely stabilized to 100 degrees C by SDS in the absence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS in the presence of mercaptoethanol. Furthermore, human fibroblast interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS under reducing conditions, but only a minor part of their activities were restored by SDS in the absence of reduction. On the contrary, human leukocyte interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS in the absence of reduction, but only a minor part of their activities were restored by SDS under reducing conditions. These data suggest that there are distinct molecular species of human interferons.", "contents": "Distinct molecular species of human interferons: requirements for stabilzation and reactivation of human leukocyte and fibroblast interferons. Human fibroblast interferon preparations were completely stabilized to 100 degrees C by sodium dodecyl sulphate (SDS) in the presence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS without mercaptoethanol. On the contarary, human leukocyte interferon preparations were completely stabilized to 100 degrees C by SDS in the absence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS in the presence of mercaptoethanol. Furthermore, human fibroblast interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS under reducing conditions, but only a minor part of their activities were restored by SDS in the absence of reduction. On the contrary, human leukocyte interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS in the absence of reduction, but only a minor part of their activities were restored by SDS under reducing conditions. These data suggest that there are distinct molecular species of human interferons."} {"id": "PMID:164522", "title": "Electroconvulsive shock and postsynaptic catecholamine effects: increased psychomotor stimulant action of apomorphine and clonidine in reserpine pretreated mice by repeated ECS.", "content": "Male mice were administered electric convulsive shocks (ECS) once daily for one (ECS X I), three (ECS X III) or seven days (ECS X VII). One (day 1), three (day 3) or six days (day 6) later they received reserpine 10 mg/kg, followed 2 hours later by clonidine, 1.5 mg/kg, and/or apomorphine, 1.5 mg/kg. Control animals received the same drug treatments but no ECS. The motor activity was recorded for 1 hour, starting immediately after the last drug injection. The behavioral depression induced by reserpine was equally pronounced in ECS-pretreated animals as in the control animals. The psychomotor stimulant effects of clonidine and/or apomorphine, given after reserpine was, however, enhanced by pretreatment with ECS X VII, DAY 1. Pretreatment wit- ECS X VII increased the motor activity also in animals given reserpine, apomorphine and clonidine at day 3 or day 6. ECS X III was also effective in this respect at day 1, whereas ECS X I, day 1, was ineffective. Mice given ECS X VII but no drug treatment showed at day 1 an increased motor activity during the initial 10 min and a decreased activity during the last 10 of the 1 hour recording period. At day 3 and day 6 after ECS X VII the motor activity was increased in comparison to that in untreated control animals during the whole 1 hour period. Animals given repeated ECS furthermore showed increased irritability and reduced body weight. The results indicate that repeated ECS increase the sensitivity of postsynaptic catecholamine receptors in the brain or alter neuronal structures which are connected to these receptors.", "contents": "Electroconvulsive shock and postsynaptic catecholamine effects: increased psychomotor stimulant action of apomorphine and clonidine in reserpine pretreated mice by repeated ECS. Male mice were administered electric convulsive shocks (ECS) once daily for one (ECS X I), three (ECS X III) or seven days (ECS X VII). One (day 1), three (day 3) or six days (day 6) later they received reserpine 10 mg/kg, followed 2 hours later by clonidine, 1.5 mg/kg, and/or apomorphine, 1.5 mg/kg. Control animals received the same drug treatments but no ECS. The motor activity was recorded for 1 hour, starting immediately after the last drug injection. The behavioral depression induced by reserpine was equally pronounced in ECS-pretreated animals as in the control animals. The psychomotor stimulant effects of clonidine and/or apomorphine, given after reserpine was, however, enhanced by pretreatment with ECS X VII, DAY 1. Pretreatment wit- ECS X VII increased the motor activity also in animals given reserpine, apomorphine and clonidine at day 3 or day 6. ECS X III was also effective in this respect at day 1, whereas ECS X I, day 1, was ineffective. Mice given ECS X VII but no drug treatment showed at day 1 an increased motor activity during the initial 10 min and a decreased activity during the last 10 of the 1 hour recording period. At day 3 and day 6 after ECS X VII the motor activity was increased in comparison to that in untreated control animals during the whole 1 hour period. Animals given repeated ECS furthermore showed increased irritability and reduced body weight. The results indicate that repeated ECS increase the sensitivity of postsynaptic catecholamine receptors in the brain or alter neuronal structures which are connected to these receptors."} {"id": "PMID:164527", "title": "Congenital granular-cell myoblastoma.", "content": "The clinical and pathologic features of congenital granular-cell myoblastoma in five infant girls are reported. One lesion, treated expectantly, progressively decreased in size and after 3 yr and 9 mo could not be detected, while two lesions which were imcompletely excised did not recur. It is suggested that congenital granular-cell myoblastoma is caused by an intrauterine stimulus, and that this stimulus may possible be production of estrogen by the fetus. Congential granular-cell myoblastoma should be treated expectantly or by limited excision, and has an excellent prognosis.", "contents": "Congenital granular-cell myoblastoma. The clinical and pathologic features of congenital granular-cell myoblastoma in five infant girls are reported. One lesion, treated expectantly, progressively decreased in size and after 3 yr and 9 mo could not be detected, while two lesions which were imcompletely excised did not recur. It is suggested that congenital granular-cell myoblastoma is caused by an intrauterine stimulus, and that this stimulus may possible be production of estrogen by the fetus. Congential granular-cell myoblastoma should be treated expectantly or by limited excision, and has an excellent prognosis."} {"id": "PMID:164528", "title": "Papillary lymphoid hyperplasia of the terminal ileum: an unusual cause of intussusception and gastrointestinal bleeding in childhood.", "content": "Papillary lymphoid hyperplasia of the terminal ileum is a benign condition associated with abdominal pain, intussusception, and gastrointestinal hemorrhage. It appears to represent a distinct clinicopathologic entity, separate from the usual idiopathic intussusception of infancy and childhood. The lesions are reasonably well circumscribed, localized in the submucosa of the terminal ileum, and composed of lymphoid tissue with prominent germinal follicles. Management by ileocolectomy resulted in complete cure with no postoperative complications in our six cases. However, many authors recommend conservative therapy. The cause is not known but there may be some relationship between these cases and intestinal adenovirus infection.", "contents": "Papillary lymphoid hyperplasia of the terminal ileum: an unusual cause of intussusception and gastrointestinal bleeding in childhood. Papillary lymphoid hyperplasia of the terminal ileum is a benign condition associated with abdominal pain, intussusception, and gastrointestinal hemorrhage. It appears to represent a distinct clinicopathologic entity, separate from the usual idiopathic intussusception of infancy and childhood. The lesions are reasonably well circumscribed, localized in the submucosa of the terminal ileum, and composed of lymphoid tissue with prominent germinal follicles. Management by ileocolectomy resulted in complete cure with no postoperative complications in our six cases. However, many authors recommend conservative therapy. The cause is not known but there may be some relationship between these cases and intestinal adenovirus infection."} {"id": "PMID:164529", "title": "Dopaminergic mechanisms of opiate actions in brain.", "content": "We have studied the interactions between morphine and a dopamine-blocking agent (haloperidol) and a dopamine precursor, L-3,4-dihydroxyphenylalanine (L-dopa). We found that haloperidol potentiated morphine-induced analgesia and enhanced morphine tolerance. Morphine-tolerant mice exhibited enhanced sensitivity to the locomotor excitatory actions of L-dopa. We propose that morphine exerts some of its central nervous actions by first interfering with dopamine-mediated synaptic transmission and then initiating compensatory changes that superficially resemble denervation supersensitivity. These compensatory changes may underlie the excitatory actions of morphine.", "contents": "Dopaminergic mechanisms of opiate actions in brain. We have studied the interactions between morphine and a dopamine-blocking agent (haloperidol) and a dopamine precursor, L-3,4-dihydroxyphenylalanine (L-dopa). We found that haloperidol potentiated morphine-induced analgesia and enhanced morphine tolerance. Morphine-tolerant mice exhibited enhanced sensitivity to the locomotor excitatory actions of L-dopa. We propose that morphine exerts some of its central nervous actions by first interfering with dopamine-mediated synaptic transmission and then initiating compensatory changes that superficially resemble denervation supersensitivity. These compensatory changes may underlie the excitatory actions of morphine."} {"id": "PMID:164530", "title": "Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate.", "content": "Neurochemical and psychopharmacological studies of rats were designed to examine four hypotheses which have been proposed to account for the development of behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate (DFP). The fact that the activity of the enzymes, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase, did not change concomitantly with behavioral measures during chronic treatment with DFP suggests that nonspecific metabolic changes are unlikely mechanisms of behavioral tolerance. Similarly, a lack of change in choline acetylase activity coupled with constantly high acetylcholine levels (140%) and low cholinesterase activity (28.5%) tends to eliminate end-product inhibition of acetylcholine synthesis as a primary mechanism of tolerance to DFP. Alpha-Methyl-p-tyrosine in doses to 150 mg/kg affected the behaviors of control and DFP-treated rats to a comparable degree, offering no support for the hypothesis that a redundant adrenergic system may replace the cholinergic system during the development of tolerance to DFP. In contrast to these various negative findings, pilocarpine was less effective in suppressing the responding of rats tolerant to DFP than that of control subjects. This confirms other evidence indicating that a decreased sensitivity of cholinergic (muscarinic) receptors is one mechanism underlying the development of tolerance to DFP.", "contents": "Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate. Neurochemical and psychopharmacological studies of rats were designed to examine four hypotheses which have been proposed to account for the development of behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate (DFP). The fact that the activity of the enzymes, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase, did not change concomitantly with behavioral measures during chronic treatment with DFP suggests that nonspecific metabolic changes are unlikely mechanisms of behavioral tolerance. Similarly, a lack of change in choline acetylase activity coupled with constantly high acetylcholine levels (140%) and low cholinesterase activity (28.5%) tends to eliminate end-product inhibition of acetylcholine synthesis as a primary mechanism of tolerance to DFP. Alpha-Methyl-p-tyrosine in doses to 150 mg/kg affected the behaviors of control and DFP-treated rats to a comparable degree, offering no support for the hypothesis that a redundant adrenergic system may replace the cholinergic system during the development of tolerance to DFP. In contrast to these various negative findings, pilocarpine was less effective in suppressing the responding of rats tolerant to DFP than that of control subjects. This confirms other evidence indicating that a decreased sensitivity of cholinergic (muscarinic) receptors is one mechanism underlying the development of tolerance to DFP."} {"id": "PMID:164531", "title": "Mechanism of blockade of neuromuscular transmission by pentobarbital.", "content": "The mechanism of block of neuromuscular transmission by pentobarbital has been studied in the frog sciatic nerve-sartorius muscle preparation by means of intracellular microelectrode and voltage clamp techniques. The resting membrane potential was decreased by pentobarbital only to a small extent (less than 15 mV) in both end-plate and non-end-plate regions. Both sodium and potassium components of end-plate current underwent drastic changes after application of pentobarbital. The peak amplitude was decreased with an apparent dissociation constant of 0.9 mM for both currents. The maximum rate of rise of end-plate current was reduced, with apparent dissociation constants of 0.9 and 1.2 mM for sodium and potassium currents, respectively. The times for sodium and potassium end-plate current to reach their peaks were shortened only to a negligible extent. The falling phase of end-plate current was greatly accelerated, sodium current being affected more than potassium current. The transient end-plate depolarization induced by iontophoretic application of acetylcholine was suppressed more effectively than end-plate potential by application of pentobarbital. The falling phase of the former was also shortened. The quantal content of end-plate potential tended to increase at 0.5 mM, but underwent no appreciable change at 1.0 and 1.4 mM. Pentobarbital has a dual action on both quantal content and end-plate membrane depending on the concentration, and the block of neuromuscular transmission is due primarily to a suppression of the end-plate sensitivity to acetylcholine. The differential effect of pentobarbital on sodium and potassium components of end-plate current is compatible with the notion that these two ionic conductances are separate entities.", "contents": "Mechanism of blockade of neuromuscular transmission by pentobarbital. The mechanism of block of neuromuscular transmission by pentobarbital has been studied in the frog sciatic nerve-sartorius muscle preparation by means of intracellular microelectrode and voltage clamp techniques. The resting membrane potential was decreased by pentobarbital only to a small extent (less than 15 mV) in both end-plate and non-end-plate regions. Both sodium and potassium components of end-plate current underwent drastic changes after application of pentobarbital. The peak amplitude was decreased with an apparent dissociation constant of 0.9 mM for both currents. The maximum rate of rise of end-plate current was reduced, with apparent dissociation constants of 0.9 and 1.2 mM for sodium and potassium currents, respectively. The times for sodium and potassium end-plate current to reach their peaks were shortened only to a negligible extent. The falling phase of end-plate current was greatly accelerated, sodium current being affected more than potassium current. The transient end-plate depolarization induced by iontophoretic application of acetylcholine was suppressed more effectively than end-plate potential by application of pentobarbital. The falling phase of the former was also shortened. The quantal content of end-plate potential tended to increase at 0.5 mM, but underwent no appreciable change at 1.0 and 1.4 mM. Pentobarbital has a dual action on both quantal content and end-plate membrane depending on the concentration, and the block of neuromuscular transmission is due primarily to a suppression of the end-plate sensitivity to acetylcholine. The differential effect of pentobarbital on sodium and potassium components of end-plate current is compatible with the notion that these two ionic conductances are separate entities."} {"id": "PMID:164532", "title": "Hormonal influences in the development of the hypermetabolic state of the liver produced by chronic administration of ethanol.", "content": "Chronic administration of ethanol to rats, either in liquid diets as the only source of food or by gastric intubation while the animals are fed ad libitum, leads to the development of a hypermetabolic state of the liver. This hypermetabolic condition of the liver can be observed independently of the feeding state of the animals. The calorigenic effects produced by ethanol in the liver, as measured in liver slices, could be reproduced by a single large dose of epinephrine. Oxygen consumption by liver slices of animals given a 2-mg/kg dose of epinephrine bitartrate increased by 40 to 50 percent. In these livers all the extra oxygen consumption, but not the basal respiration, could be abolished by ouabain, an inhibitor of the sodium pump. Dinitrophenol did not affect the respiratory rate in the liver of epinephrine-treated animals while markedly increasing that in controls. In the liver of treated animals, the activatory effect of dinitrophenol could be recovered in the presence of ouabain. The calorigenic effect of epinephrine in the liver was found to be completely abolished by phentolamine (alpha adrenergic blocker) but was not modified by DL-propranolol (beta adrenergic blocker). Also, the calorigenic effects produced by epinephrine could not be seen in thyroidectomized animals or by incubating the liver slices in a calcium-free medium. Thyroidectomy and administration of phentolamine markedly reduced and adrenalectomy completely abolished the hypermetabolic state produced in the liver of rats by chronic administration of ethanol.", "contents": "Hormonal influences in the development of the hypermetabolic state of the liver produced by chronic administration of ethanol. Chronic administration of ethanol to rats, either in liquid diets as the only source of food or by gastric intubation while the animals are fed ad libitum, leads to the development of a hypermetabolic state of the liver. This hypermetabolic condition of the liver can be observed independently of the feeding state of the animals. The calorigenic effects produced by ethanol in the liver, as measured in liver slices, could be reproduced by a single large dose of epinephrine. Oxygen consumption by liver slices of animals given a 2-mg/kg dose of epinephrine bitartrate increased by 40 to 50 percent. In these livers all the extra oxygen consumption, but not the basal respiration, could be abolished by ouabain, an inhibitor of the sodium pump. Dinitrophenol did not affect the respiratory rate in the liver of epinephrine-treated animals while markedly increasing that in controls. In the liver of treated animals, the activatory effect of dinitrophenol could be recovered in the presence of ouabain. The calorigenic effect of epinephrine in the liver was found to be completely abolished by phentolamine (alpha adrenergic blocker) but was not modified by DL-propranolol (beta adrenergic blocker). Also, the calorigenic effects produced by epinephrine could not be seen in thyroidectomized animals or by incubating the liver slices in a calcium-free medium. Thyroidectomy and administration of phentolamine markedly reduced and adrenalectomy completely abolished the hypermetabolic state produced in the liver of rats by chronic administration of ethanol."} {"id": "PMID:164533", "title": "Potentiation of carbon tetrachloride-induced hepatotoxicity in alloxan- or strepto- zotocin-diabetic rats.", "content": "Studies were performed to examine the effects of alloxan- or streptozotocin-induced diabetes on carbon tetrachloride (CCl4) liver injury. Male rats were pretreated with single i.v. injections of alloxan monohydrate (40 or 80 mg/kg) or streptozotocin (65 mg/kg). A challenging dose of CCl4 (0.1 ml/kg i.p.) was given to rats 4 days after alloxan pretreatment or 5 days after streptozotocin pretreatment, and the animals were sacrificed 24 hours later. Biochemical and morphologic evidence was obtained to show that pretreatment with the diabetogenic agents markedly enhanced CCl4-induced hepatotoxity. The challenging dose of CCl4 had no effect on the serum glutamic pyruvic transaminase (SGPT) activity in control rats. However, the administration of this dose of CCl4 to rats pretreated with 40 and 80 mg/kg of alloxan as well as to rats pretreated with streptozotocin resulted in 11-, 68-, and 32-fold increases, respectively, in SGPT activity. Hepatic triglyceride concentrations in the diabetic rats were also markedly elevated above control values after CCl4 challenge. Alloxan- or streptozotocin-pretreatment alone did not enhance these biochemical parameters of liver injury. Hepatic glucose-6-phosphatase activity, which increased in the rats given a diabetogenic agent, was lowered as a result of CCl4 injection. Insulin treatment of rats given alloxan (80 mg/kg) markedly protected against CCl4-induced hepatotoxicity. The severity of the morphologic changes in diabetic rats given CCl4 correlated with the biochemical findings.", "contents": "Potentiation of carbon tetrachloride-induced hepatotoxicity in alloxan- or strepto- zotocin-diabetic rats. Studies were performed to examine the effects of alloxan- or streptozotocin-induced diabetes on carbon tetrachloride (CCl4) liver injury. Male rats were pretreated with single i.v. injections of alloxan monohydrate (40 or 80 mg/kg) or streptozotocin (65 mg/kg). A challenging dose of CCl4 (0.1 ml/kg i.p.) was given to rats 4 days after alloxan pretreatment or 5 days after streptozotocin pretreatment, and the animals were sacrificed 24 hours later. Biochemical and morphologic evidence was obtained to show that pretreatment with the diabetogenic agents markedly enhanced CCl4-induced hepatotoxity. The challenging dose of CCl4 had no effect on the serum glutamic pyruvic transaminase (SGPT) activity in control rats. However, the administration of this dose of CCl4 to rats pretreated with 40 and 80 mg/kg of alloxan as well as to rats pretreated with streptozotocin resulted in 11-, 68-, and 32-fold increases, respectively, in SGPT activity. Hepatic triglyceride concentrations in the diabetic rats were also markedly elevated above control values after CCl4 challenge. Alloxan- or streptozotocin-pretreatment alone did not enhance these biochemical parameters of liver injury. Hepatic glucose-6-phosphatase activity, which increased in the rats given a diabetogenic agent, was lowered as a result of CCl4 injection. Insulin treatment of rats given alloxan (80 mg/kg) markedly protected against CCl4-induced hepatotoxicity. The severity of the morphologic changes in diabetic rats given CCl4 correlated with the biochemical findings."} {"id": "PMID:164534", "title": "Influence of prostaglandins E1 and F2alpha on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels.", "content": "The effects of prostaglandins E1 (PGE1) and F2alpha) on the pulmonary vascular bed were studied in the intact dog under conditions of controlled pulmonary blood flow. PGF2alpha increased lobar arterial and venous pressure when injected or infused into the lobar, artery. The pressor response was dose-related and doses as low as 0.03 and 0.1 mug, which established concentrations of 0.1 to 0.3 ng/ml in lobar arterial blood, increased pulmonary vascular resistance. PGF2alpha also increased airway resistance in the left lower lobe. However, the effects of this substance on the vascular bed were not related to its effects on bronchomotor tone since similar pressor responses were observed in normal and nonrespiring lobes, PGE1 decreased pressure in the lobar artery and vein when infused into the lobar artery and the effects of PGE1 and PGF2alpha on the pulmonary vascular bed were similar when the lung was perfused with dextran or with blood. PGF2alpha increased isometric tension in isolated helical segments of lobar vein 3 to 5 mm in diameter but was without effect on arterial segments of the same diameter. The increase in isometric tension in the venous segments with PGF2alpha was associated with a significant increase in intracellular levels of guanosine 3',5'-monophosphate (cGMP) but no change in adenosine 3',5'-monophosphate (cAMP) levels. PGE1 decreased isometric tension in both arterial and venous segments and the decrease in tension was accompanied by a significant elevation in smooth muscle cAMP levels and a small but significant reduction in vein cGMP. Results of the present study indicate that PGF2alpha increases pulmonary resistance by constricting lobar veins and to a lesser extent vessels upstream in the precapillary bed whereas PGE1 dilates lobar veins and upstream vessels. These results suggest that PGE1-induced vasodilation may be mediated by an increase in cAMP levels while PGF2alpha-induced venoconstriction may be related to increased smooth muscle levels of cGMP.", "contents": "Influence of prostaglandins E1 and F2alpha on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels. The effects of prostaglandins E1 (PGE1) and F2alpha) on the pulmonary vascular bed were studied in the intact dog under conditions of controlled pulmonary blood flow. PGF2alpha increased lobar arterial and venous pressure when injected or infused into the lobar, artery. The pressor response was dose-related and doses as low as 0.03 and 0.1 mug, which established concentrations of 0.1 to 0.3 ng/ml in lobar arterial blood, increased pulmonary vascular resistance. PGF2alpha also increased airway resistance in the left lower lobe. However, the effects of this substance on the vascular bed were not related to its effects on bronchomotor tone since similar pressor responses were observed in normal and nonrespiring lobes, PGE1 decreased pressure in the lobar artery and vein when infused into the lobar artery and the effects of PGE1 and PGF2alpha on the pulmonary vascular bed were similar when the lung was perfused with dextran or with blood. PGF2alpha increased isometric tension in isolated helical segments of lobar vein 3 to 5 mm in diameter but was without effect on arterial segments of the same diameter. The increase in isometric tension in the venous segments with PGF2alpha was associated with a significant increase in intracellular levels of guanosine 3',5'-monophosphate (cGMP) but no change in adenosine 3',5'-monophosphate (cAMP) levels. PGE1 decreased isometric tension in both arterial and venous segments and the decrease in tension was accompanied by a significant elevation in smooth muscle cAMP levels and a small but significant reduction in vein cGMP. Results of the present study indicate that PGF2alpha increases pulmonary resistance by constricting lobar veins and to a lesser extent vessels upstream in the precapillary bed whereas PGE1 dilates lobar veins and upstream vessels. These results suggest that PGE1-induced vasodilation may be mediated by an increase in cAMP levels while PGF2alpha-induced venoconstriction may be related to increased smooth muscle levels of cGMP."} {"id": "PMID:164535", "title": "Two descending nerve pathways activated by distension of guinea-pig small intestine.", "content": "1. Intracellular recordings were made from myenteric neurones of the guinea-pig small intestine in preparations which had a synaptic input from an orally situated segment of intestine. 2. Excitatory synaptic potentials could be evoked in most neurones by distension of the attached intestinal segment. 3. It was possible to distinguish two distinct firing patterns of synaptic potentials in response to distension. A transient short latency discharge was recorded from some neurones. From the others, a persistent synaptic discharge was recorded only after a long latency (2-11 sec). 4. Distension of intestinal segments evoked short latency transient inhibitory junction potentials in the circular muscle layer followed by excitatory junction potentials in both the circular and longitudinal muscle layers. 5. It is suggested that distension may cause both descending inhibition and, after a delay, descending excitation of the guinea-pig small intestine.", "contents": "Two descending nerve pathways activated by distension of guinea-pig small intestine. 1. Intracellular recordings were made from myenteric neurones of the guinea-pig small intestine in preparations which had a synaptic input from an orally situated segment of intestine. 2. Excitatory synaptic potentials could be evoked in most neurones by distension of the attached intestinal segment. 3. It was possible to distinguish two distinct firing patterns of synaptic potentials in response to distension. A transient short latency discharge was recorded from some neurones. From the others, a persistent synaptic discharge was recorded only after a long latency (2-11 sec). 4. Distension of intestinal segments evoked short latency transient inhibitory junction potentials in the circular muscle layer followed by excitatory junction potentials in both the circular and longitudinal muscle layers. 5. It is suggested that distension may cause both descending inhibition and, after a delay, descending excitation of the guinea-pig small intestine."} {"id": "PMID:164536", "title": "Estimates of statistical release parameters from crayfish and frog neuromuscular junctions.", "content": "1. Transmitter release at crayfish and frog neuromuscular junctions was studied by recording synaptic potentials with extracellular or intracellular glass micro-electrodes. 2. The binomial release parameters n and p were calculated using the experimental observations for the mean number of quanta (m) released in a series of trials, the variance (var) of the quantum content distribution and the number of transmission failures (n-o). 3. In one series of experiments on frog neuromuscular junction, action potentials were blocked by tetrodotoxin. Transmitter release was limited to a circumscribed part of the nerve terminal by focal stimulation with a glass micro-electrode. Values for m were between 0-6 and 5-7 and calculated values for n ranged from 3 to 23. p was between 0-05 and 0-48. In a second series of experiments on frog neuromuscular junction transmitter release was evoked by conventional stimulation of the nerve trunk in Mg-Ringer. m was mostly between 20 and 60 and in the same experiments n was calculated to be between 70 and 125. Values for p ranged from 0-25 to 0-48. 4. It can be concluded from the present results that transmitter release at frog neuromuscular junction is described by binomial statistics as is the case for neuromuscular junction of crayfish. 5. In comparing the values for n for the two series of experiments on frog neuromuscular junction it appears that n is dependent on the length of the activated synaptic contact. The numbers for n calculated from frog neuromuscular junction are of the same order of magnitude as the number of 'active zones' seen in the corresponding length of the synaptic nerve terminal.", "contents": "Estimates of statistical release parameters from crayfish and frog neuromuscular junctions. 1. Transmitter release at crayfish and frog neuromuscular junctions was studied by recording synaptic potentials with extracellular or intracellular glass micro-electrodes. 2. The binomial release parameters n and p were calculated using the experimental observations for the mean number of quanta (m) released in a series of trials, the variance (var) of the quantum content distribution and the number of transmission failures (n-o). 3. In one series of experiments on frog neuromuscular junction, action potentials were blocked by tetrodotoxin. Transmitter release was limited to a circumscribed part of the nerve terminal by focal stimulation with a glass micro-electrode. Values for m were between 0-6 and 5-7 and calculated values for n ranged from 3 to 23. p was between 0-05 and 0-48. In a second series of experiments on frog neuromuscular junction transmitter release was evoked by conventional stimulation of the nerve trunk in Mg-Ringer. m was mostly between 20 and 60 and in the same experiments n was calculated to be between 70 and 125. Values for p ranged from 0-25 to 0-48. 4. It can be concluded from the present results that transmitter release at frog neuromuscular junction is described by binomial statistics as is the case for neuromuscular junction of crayfish. 5. In comparing the values for n for the two series of experiments on frog neuromuscular junction it appears that n is dependent on the length of the activated synaptic contact. The numbers for n calculated from frog neuromuscular junction are of the same order of magnitude as the number of 'active zones' seen in the corresponding length of the synaptic nerve terminal."} {"id": "PMID:164539", "title": "Nursing staff training for an effective geropsychiatric environment.", "content": "In describing an early training program of the Gerontological Manpower Project, we have attempted to demonstrate that short-term, on-site training with a frim theoretical and empirical base, can be an effective vehicle for translating research into application. In this case, research and theory based on the importance of the environment as therapeutic, and directed to maximizing geriatric patient independence was incorporated into a geriatric training programmthis was delivered to personnel working with the elderly in two institutional settings, differing in geriatric patient population and service orientation. To improve the effectiveness of future training programs, extensive evaluative research was included in the training processes. Although results were predictably tentative, they did yield much useful information both for subsequent program design as well as reinforcing a need for this process itself. Finally, a very satisfying and beneficial result of this project, as specified by the research staff and all participants, is that effective application of research results via appropriate training mechanisms are easily within reach of the nurse-practioner, and the oft-desired bridge between academia and the service delivery system is truly a collaborative reality.", "contents": "Nursing staff training for an effective geropsychiatric environment. In describing an early training program of the Gerontological Manpower Project, we have attempted to demonstrate that short-term, on-site training with a frim theoretical and empirical base, can be an effective vehicle for translating research into application. In this case, research and theory based on the importance of the environment as therapeutic, and directed to maximizing geriatric patient independence was incorporated into a geriatric training programmthis was delivered to personnel working with the elderly in two institutional settings, differing in geriatric patient population and service orientation. To improve the effectiveness of future training programs, extensive evaluative research was included in the training processes. Although results were predictably tentative, they did yield much useful information both for subsequent program design as well as reinforcing a need for this process itself. Finally, a very satisfying and beneficial result of this project, as specified by the research staff and all participants, is that effective application of research results via appropriate training mechanisms are easily within reach of the nurse-practioner, and the oft-desired bridge between academia and the service delivery system is truly a collaborative reality."} {"id": "PMID:164540", "title": "The dysfunction of DSM-II (Diagnostic and Statistical Manual of Mental Disorders).", "content": "The task of seeking alternatives to a classification system such as DSM-II that will maximize its benefits and minimize its limitation is a complex and arduous one. There are no clear-cut answers. Certain issues had been elaborated on here. The task at hand is one that must be approached on a multiprofessional basis seeking to integrate a variety of theoretical bases into a functional conceptual framework that will accomplish the purpose of a classification scheme. There is also need to conduct systematic data collection in an effort to determine operational definitions related to the phenomenon that is being studied. There is a movement by some professionals to have more emphasis placed on the social functioning level of the individual and his significant othersmif a concerted effort is not begun to look at this problem it will remain unchanged for the most part or other interested professionals will have changed it with little impact from nursing.", "contents": "The dysfunction of DSM-II (Diagnostic and Statistical Manual of Mental Disorders). The task of seeking alternatives to a classification system such as DSM-II that will maximize its benefits and minimize its limitation is a complex and arduous one. There are no clear-cut answers. Certain issues had been elaborated on here. The task at hand is one that must be approached on a multiprofessional basis seeking to integrate a variety of theoretical bases into a functional conceptual framework that will accomplish the purpose of a classification scheme. There is also need to conduct systematic data collection in an effort to determine operational definitions related to the phenomenon that is being studied. There is a movement by some professionals to have more emphasis placed on the social functioning level of the individual and his significant othersmif a concerted effort is not begun to look at this problem it will remain unchanged for the most part or other interested professionals will have changed it with little impact from nursing."} {"id": "PMID:164545", "title": "Stimulation of protein synthesis in vivo in immature mouse testis by FSH.", "content": "Human pituitary FSH was found to increase the incorporation of tritiated lysine into testicular protein in prepubertal mice in vivo. Radioactivity was measured in washed trichloracetic acid precipitates prepared from crude testicular homogenates. The time of maximum response was 8 to 16 hr after subcutaneous injection of the hormone. This was considerably later than the maximum response in vitro reported by other workers. Neither HCG nor dibutyryl cyclic 3',5'-adenosine monophosphate had a significant effect on the incorporation of lysine.", "contents": "Stimulation of protein synthesis in vivo in immature mouse testis by FSH. Human pituitary FSH was found to increase the incorporation of tritiated lysine into testicular protein in prepubertal mice in vivo. Radioactivity was measured in washed trichloracetic acid precipitates prepared from crude testicular homogenates. The time of maximum response was 8 to 16 hr after subcutaneous injection of the hormone. This was considerably later than the maximum response in vitro reported by other workers. Neither HCG nor dibutyryl cyclic 3',5'-adenosine monophosphate had a significant effect on the incorporation of lysine."} {"id": "PMID:164546", "title": "Ultrastructural relationships between decidua, trophoblast and lymphocytes at the beginning of human pregnancy.", "content": "Between the 20th and 40th day of pregnancy, human decidual cells in the endometrial connective tissue come into direct contact with the trophoblastic cells eroding the stromal tissue. Fibrillar deposits of maternal origin were randomly distributed between the maternal and fetal sites and did not form a continuous barrier. Structural features were prominent in the maternal and embryonic cells. Large decidual cells were intermingled with trophoblastic cells, and there was little intercellular material. Small developing decidual cells arose around the maternal precapillary arterioles and capillaries and were closely accompanied by lymphocytes. Fully developed decidual cells exhibited a fine structure characteristic of a state of active secretion, and trophoblastic cells gave structural indications of producing protein. The aggregates of decidual and trophoblastic cells in the human endometrium during early pregnancy ('deciduotrophoblastic complex') may function as a local humoral regulator releasing chemical factors and partaking in the establishment of immunological privilege at implantation.", "contents": "Ultrastructural relationships between decidua, trophoblast and lymphocytes at the beginning of human pregnancy. Between the 20th and 40th day of pregnancy, human decidual cells in the endometrial connective tissue come into direct contact with the trophoblastic cells eroding the stromal tissue. Fibrillar deposits of maternal origin were randomly distributed between the maternal and fetal sites and did not form a continuous barrier. Structural features were prominent in the maternal and embryonic cells. Large decidual cells were intermingled with trophoblastic cells, and there was little intercellular material. Small developing decidual cells arose around the maternal precapillary arterioles and capillaries and were closely accompanied by lymphocytes. Fully developed decidual cells exhibited a fine structure characteristic of a state of active secretion, and trophoblastic cells gave structural indications of producing protein. The aggregates of decidual and trophoblastic cells in the human endometrium during early pregnancy ('deciduotrophoblastic complex') may function as a local humoral regulator releasing chemical factors and partaking in the establishment of immunological privilege at implantation."} {"id": "PMID:164547", "title": "The coagulation of insoluble and basic proteins from rat siminal vesicle secretion with vesiculase: influence of collagenase-like peptidase from rat testis.", "content": "Proteins from the secretion of rat seminal vesicles were fractionated to yield (i) insoluble protein, (ii) basic proteins (soluble in the presence of urea) and (iii) neutral plus acidic proteins. The first two are necessary for the formation in vitro of a coagulum which is very similar to the copulatory plug. Collagenase-like peptidase from rat testis degrades both protein fractions and prevents coagulum formation.", "contents": "The coagulation of insoluble and basic proteins from rat siminal vesicle secretion with vesiculase: influence of collagenase-like peptidase from rat testis. Proteins from the secretion of rat seminal vesicles were fractionated to yield (i) insoluble protein, (ii) basic proteins (soluble in the presence of urea) and (iii) neutral plus acidic proteins. The first two are necessary for the formation in vitro of a coagulum which is very similar to the copulatory plug. Collagenase-like peptidase from rat testis degrades both protein fractions and prevents coagulum formation."} {"id": "PMID:164548", "title": "Implantation in ovariectomized mice treated with dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP).", "content": "Experiments are described that demonstrate that uterine intraluminal injection of a 1-25 mM-solution of dibutyryl cyclic AMP (dcAMP) in phosphate buffered saline (PBS) induced implantation in ovariectomized pregnant mice. Pretreatment with progesterone was essential for this effect. When PBS was injected alone, it did not induce implantation in mice treated with progesterone. Bilateral adrenalectomy had no effect on the ability of dcAMP to substitute for oestradiol, showing that the effect was not due to dcAMP-induced oestrogen synthesis in the adrenal cortex. It is suggested that the dcAMP may act at the level of the uterus, the embryo, or both.", "contents": "Implantation in ovariectomized mice treated with dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). Experiments are described that demonstrate that uterine intraluminal injection of a 1-25 mM-solution of dibutyryl cyclic AMP (dcAMP) in phosphate buffered saline (PBS) induced implantation in ovariectomized pregnant mice. Pretreatment with progesterone was essential for this effect. When PBS was injected alone, it did not induce implantation in mice treated with progesterone. Bilateral adrenalectomy had no effect on the ability of dcAMP to substitute for oestradiol, showing that the effect was not due to dcAMP-induced oestrogen synthesis in the adrenal cortex. It is suggested that the dcAMP may act at the level of the uterus, the embryo, or both."} {"id": "PMID:164550", "title": "Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.", "content": "Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-erythro-beta-hydroxyl-DL-aspartic acid (4) which could not be diazotized. The dimethyl ester of 1 was coupled with carbobenzoxyglycine to give the blocked dipeptide 7a which was deblocked to give dimethyl glycel-erythro-beta-hydroxy-DL-aspartate hydrochloride (8). Diazotization of 8 gave impure diazo compound 9 which on reaction with HCl gave the chloro compound 10. The methods of isolation, assay, and inhibition of ASase are discribed. At 10 mM concentrations 10, 1, and its D and L enantiomers inhibit ASase by 45, 47, 36 and 66 percent, respectively.", "contents": "Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives. Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-erythro-beta-hydroxyl-DL-aspartic acid (4) which could not be diazotized. The dimethyl ester of 1 was coupled with carbobenzoxyglycine to give the blocked dipeptide 7a which was deblocked to give dimethyl glycel-erythro-beta-hydroxy-DL-aspartate hydrochloride (8). Diazotization of 8 gave impure diazo compound 9 which on reaction with HCl gave the chloro compound 10. The methods of isolation, assay, and inhibition of ASase are discribed. At 10 mM concentrations 10, 1, and its D and L enantiomers inhibit ASase by 45, 47, 36 and 66 percent, respectively."} {"id": "PMID:164551", "title": "Adrenocorticotropin. 47. Synthesis and biological activity of adrenocorticotropic peptides modified at the tryptophan position.", "content": "Three biologically active peptides, [9-beta-(1-naphthyl)alanine]-ACTH-(1-19), [9-Ni-formyltryptophanl-ACTH-1(1-19), and (8-lysine,9-phenylalaninel-ACTH-1(1-9), have been synthesized by the solid-phase method. All of the synthetic peptides showed diminished biological activity compared to ACTH-(1-19). It was also shown that the steroidogenic and lipolytic activities of ACTH-(1-19) were not inhibited by [8-lysine,.-phenylalanine]-ACTH-(1-19).", "contents": "Adrenocorticotropin. 47. Synthesis and biological activity of adrenocorticotropic peptides modified at the tryptophan position. Three biologically active peptides, [9-beta-(1-naphthyl)alanine]-ACTH-(1-19), [9-Ni-formyltryptophanl-ACTH-1(1-19), and (8-lysine,9-phenylalaninel-ACTH-1(1-9), have been synthesized by the solid-phase method. All of the synthetic peptides showed diminished biological activity compared to ACTH-(1-19). It was also shown that the steroidogenic and lipolytic activities of ACTH-(1-19) were not inhibited by [8-lysine,.-phenylalanine]-ACTH-(1-19)."} {"id": "PMID:164552", "title": "Distinction between Duchenne and other muscular dystrophies by ribosomal protein synthesis.", "content": "Ribosome concentration, ribosome distribution on sucrose density gradients, and in-vitro ribosomal amino-acid incorporation (noncollagen and collagen synthesis) were studied in muscle biopsy samples obtained from 30 patients with Duchenne muscular dystrophy, seven patients with Becker muscular dystrophy, and 10 with facioscapulohumeral muscular dystrophy. Ribosome concentration was normal in Duchenne and facioscapulohumeral and decreased in Becker muscular dystrophy. Distribution of ribosomes in sucrose density gradients showed abnormalities (sharp monosomal peak and fewer polyribosomes) only in Duchenne muscular dystrophy and was normal in the other two types. In-vitro amino-acid incorporation of ribosomes in Duchenne muscular dystrophy revealed high collagen and low noncollagen synthesis of the heavy polyribosomes. This abnormality is controlled by an undetermined enzymatic factor belonging to the soluble enzyme fraction. Supplementation of the dystrophic heavy polyribosomes with normal soluble enzymes restored the synthesis of collagen to that of the controls. Heavy polyribosomes extracted from normals or from carriers produce proportionately more collagen in the presence of soluble enzyme fraction from Duchenne muscular dystrophy than in the presence of their homologous enzymes. In Becker muscular dystrophy, both noncollagen and collagen synthesis of the heavy polyribosomes were increased, under the influence of ribosomal factors. The different protein synthesis in Duchenne and Becker muscular dystrophies suggests that these conditions are non-allelic. In facioscapulohumeral muscular dystrophy the changes in protein synthesis occurred only in the early stage of the disease and consisted of increased noncollagen synthesis of the light polyribosomes, while the heavy polyribosomes had normal activity including collagen synthesis. This reaction was controlled by ribosomal factors.", "contents": "Distinction between Duchenne and other muscular dystrophies by ribosomal protein synthesis. Ribosome concentration, ribosome distribution on sucrose density gradients, and in-vitro ribosomal amino-acid incorporation (noncollagen and collagen synthesis) were studied in muscle biopsy samples obtained from 30 patients with Duchenne muscular dystrophy, seven patients with Becker muscular dystrophy, and 10 with facioscapulohumeral muscular dystrophy. Ribosome concentration was normal in Duchenne and facioscapulohumeral and decreased in Becker muscular dystrophy. Distribution of ribosomes in sucrose density gradients showed abnormalities (sharp monosomal peak and fewer polyribosomes) only in Duchenne muscular dystrophy and was normal in the other two types. In-vitro amino-acid incorporation of ribosomes in Duchenne muscular dystrophy revealed high collagen and low noncollagen synthesis of the heavy polyribosomes. This abnormality is controlled by an undetermined enzymatic factor belonging to the soluble enzyme fraction. Supplementation of the dystrophic heavy polyribosomes with normal soluble enzymes restored the synthesis of collagen to that of the controls. Heavy polyribosomes extracted from normals or from carriers produce proportionately more collagen in the presence of soluble enzyme fraction from Duchenne muscular dystrophy than in the presence of their homologous enzymes. In Becker muscular dystrophy, both noncollagen and collagen synthesis of the heavy polyribosomes were increased, under the influence of ribosomal factors. The different protein synthesis in Duchenne and Becker muscular dystrophies suggests that these conditions are non-allelic. In facioscapulohumeral muscular dystrophy the changes in protein synthesis occurred only in the early stage of the disease and consisted of increased noncollagen synthesis of the light polyribosomes, while the heavy polyribosomes had normal activity including collagen synthesis. This reaction was controlled by ribosomal factors."} {"id": "PMID:164553", "title": "Bilayer structure in phospholipid-cytochrome c model membranes.", "content": "Lipid protein interactions in biological membranes differ markedly depending on whether the protein is intrinsic or extrinsic. These interactions are studied using lipid spin labels diffused into model systems consisting of phospholipid bilayers and a specific protein. Recently, an intrinsic protein complex, cytochrome oxidase, was examined and the data suggest there is a boundary layer of immobilized lipid between the hydrophobic protein surfaces and adjacent fluid bilayer regions. In the present study, a typical extrinsic protein, cytochrome c, was complexed with a cardiolipin/lecithin (1:4 by weight) mixture. The phospholipids in the presence and absence of cytochrome c exhibit typical bilayer behavior as jedged by four spin-labeling criteria: fluidity gradient, spectral anisotropy of oriented bilayers, response to hydration and the polarity profile. Any effects of cytochrome c on the ESR spectra of lipid spin labels are small, in contrast to the effects of intrinsic proteins. These data are consistent with electrostatic binding of cytochrome c to the charged groups of the phospholipids, and indicate that the presence of extrinsic proteins will not interfere with measurements of boundary lipid in intact biological membranes.", "contents": "Bilayer structure in phospholipid-cytochrome c model membranes. Lipid protein interactions in biological membranes differ markedly depending on whether the protein is intrinsic or extrinsic. These interactions are studied using lipid spin labels diffused into model systems consisting of phospholipid bilayers and a specific protein. Recently, an intrinsic protein complex, cytochrome oxidase, was examined and the data suggest there is a boundary layer of immobilized lipid between the hydrophobic protein surfaces and adjacent fluid bilayer regions. In the present study, a typical extrinsic protein, cytochrome c, was complexed with a cardiolipin/lecithin (1:4 by weight) mixture. The phospholipids in the presence and absence of cytochrome c exhibit typical bilayer behavior as jedged by four spin-labeling criteria: fluidity gradient, spectral anisotropy of oriented bilayers, response to hydration and the polarity profile. Any effects of cytochrome c on the ESR spectra of lipid spin labels are small, in contrast to the effects of intrinsic proteins. These data are consistent with electrostatic binding of cytochrome c to the charged groups of the phospholipids, and indicate that the presence of extrinsic proteins will not interfere with measurements of boundary lipid in intact biological membranes."} {"id": "PMID:164554", "title": "Membrane proteins and urea and acetamide transport in the human erythrocyte.", "content": "Previous studies have shown that urea and acetamide traverse the erythrocyte membrane by way of facilitated diffusion. The nature of this selective pathway is unknown. The present studies investigate the effects of proteolytic enzymes and crosslinking agents on amide transport. Cleavage of the erythrocyte membrane surface by pronase or trypsin had no effect on urea and acetamide permeability or inhibition by phloretin. These findings suggest that the sialoglycopeptide segment of the sialoglycoproteins is not critical to urea and acetamide transport. In addition, extensive crosslinking of membrane proteins with glutaraldehyde had no effect on amide transport in the absence or presence of phloretin.", "contents": "Membrane proteins and urea and acetamide transport in the human erythrocyte. Previous studies have shown that urea and acetamide traverse the erythrocyte membrane by way of facilitated diffusion. The nature of this selective pathway is unknown. The present studies investigate the effects of proteolytic enzymes and crosslinking agents on amide transport. Cleavage of the erythrocyte membrane surface by pronase or trypsin had no effect on urea and acetamide permeability or inhibition by phloretin. These findings suggest that the sialoglycopeptide segment of the sialoglycoproteins is not critical to urea and acetamide transport. In addition, extensive crosslinking of membrane proteins with glutaraldehyde had no effect on amide transport in the absence or presence of phloretin."} {"id": "PMID:164555", "title": "Isolation and characterization of the plasma membrane from Yoshida hepatoma cells.", "content": "Plasma membranes isolated from Yoshida ascites hepatoma AH-130 by a modification of the method of T.K. Ray (Biochim. Biophys. Acta 196:1, 1970), were subfractionated into three fractions having densities (d) 1.12, 1.14 and 1.16 by discontinuous sucrose density-gradient. Membrane subfractions were characterized by electron-microscopy, by assay of marker enzymes and by lipid composition. All subfractions appeared to be essentially free from whole mitochondria, lysosomes and nuclei. Subfraction d 1.16 had the highest 5'-nucleotidase, Mg++-ATPase and (Na+ +K+)-ATPase activities; cytochrome c oxidase was undetectable in any fraction and glucose-6-phosphatase was measurable only in fraction d 1.14 and 1.16. Cyclic AMP phosphodiesterase was nearly equally distributed in the fractions. Adenylate cyclase, 5'-nucleotidase and Mg++-ATPase activities of tumor membrane were lower with respect to liver plasma membrane, while cyclic AMP phosphodiesterase and (Na\" +K+)-ATPase were found to have similar activities in the two membrane preparations. With respect to liver membrane, hepatoma membrane contained a higher amount of glycolipids and a higher amount of phospholipids accounted for mainly by sphingomyelin, phosphatidylserine and phosphatidic acid. The possible significance of the decrease of adenylate activity in the hepatoma membrane is briefly discussed.", "contents": "Isolation and characterization of the plasma membrane from Yoshida hepatoma cells. Plasma membranes isolated from Yoshida ascites hepatoma AH-130 by a modification of the method of T.K. Ray (Biochim. Biophys. Acta 196:1, 1970), were subfractionated into three fractions having densities (d) 1.12, 1.14 and 1.16 by discontinuous sucrose density-gradient. Membrane subfractions were characterized by electron-microscopy, by assay of marker enzymes and by lipid composition. All subfractions appeared to be essentially free from whole mitochondria, lysosomes and nuclei. Subfraction d 1.16 had the highest 5'-nucleotidase, Mg++-ATPase and (Na+ +K+)-ATPase activities; cytochrome c oxidase was undetectable in any fraction and glucose-6-phosphatase was measurable only in fraction d 1.14 and 1.16. Cyclic AMP phosphodiesterase was nearly equally distributed in the fractions. Adenylate cyclase, 5'-nucleotidase and Mg++-ATPase activities of tumor membrane were lower with respect to liver plasma membrane, while cyclic AMP phosphodiesterase and (Na\" +K+)-ATPase were found to have similar activities in the two membrane preparations. With respect to liver membrane, hepatoma membrane contained a higher amount of glycolipids and a higher amount of phospholipids accounted for mainly by sphingomyelin, phosphatidylserine and phosphatidic acid. The possible significance of the decrease of adenylate activity in the hepatoma membrane is briefly discussed."} {"id": "PMID:164558", "title": "Primary tissue culture of human wart-derived epidermal cells (keratinocytes).", "content": "The formation of human skin warts may depend on transformation by human papilloma virus or result from a productive virus infection. To explore this problem, methods were developed for the primary tissue culture of epidermal cells (keratinocytes) derived from wart tissues and normal skin. Wart-derived keratinocytes continued to proliferate for periods exceeding 3 months, but the patterns of cell growth were identical to normal keratinocytes. Electron microscopic and immunohistologic examination of wart-derived cultures did not evidence virion assembly.", "contents": "Primary tissue culture of human wart-derived epidermal cells (keratinocytes). The formation of human skin warts may depend on transformation by human papilloma virus or result from a productive virus infection. To explore this problem, methods were developed for the primary tissue culture of epidermal cells (keratinocytes) derived from wart tissues and normal skin. Wart-derived keratinocytes continued to proliferate for periods exceeding 3 months, but the patterns of cell growth were identical to normal keratinocytes. Electron microscopic and immunohistologic examination of wart-derived cultures did not evidence virion assembly."} {"id": "PMID:164559", "title": "Differences between soluble complement-fixing antigens derived from P3HR-1, RAJI, and Hk-Ly-28 cell lines.", "content": "Soluble complement-fixing (CF) antigens of the virus-producing and virus-nonproducing P3HR-1 and RAJI Burkitt lymphoma cell lines and Hk-Ly-28 nasopharyngeal cancer cell line, identified by use of viral capsid antigen-positive human sera, could readily be distinguished by differences in their stability to chemical and physical conditions. The P3HR-1 soluble CF antigen lost titer when heated or exposed to acid perchlorate under conditions in which RAJI and Hk-Ly-28 soluble antigens were stable. Differences in solubility were also found. These results contribute not only to the interpretation of the relationship of Epstein-Barr virus (EBV)-associated components of RAJI to P3HR-1 and Hk-Ly-28 cell lysates but also to the selection of conditions for the development of identification tests and purification procedures for CF antigens and antibodies of Burkitt's lymphoma, nasopharyngeal cancer, and other EBV-associated tumors.", "contents": "Differences between soluble complement-fixing antigens derived from P3HR-1, RAJI, and Hk-Ly-28 cell lines. Soluble complement-fixing (CF) antigens of the virus-producing and virus-nonproducing P3HR-1 and RAJI Burkitt lymphoma cell lines and Hk-Ly-28 nasopharyngeal cancer cell line, identified by use of viral capsid antigen-positive human sera, could readily be distinguished by differences in their stability to chemical and physical conditions. The P3HR-1 soluble CF antigen lost titer when heated or exposed to acid perchlorate under conditions in which RAJI and Hk-Ly-28 soluble antigens were stable. Differences in solubility were also found. These results contribute not only to the interpretation of the relationship of Epstein-Barr virus (EBV)-associated components of RAJI to P3HR-1 and Hk-Ly-28 cell lysates but also to the selection of conditions for the development of identification tests and purification procedures for CF antigens and antibodies of Burkitt's lymphoma, nasopharyngeal cancer, and other EBV-associated tumors."} {"id": "PMID:164560", "title": "Pathogenic and serologic studies of Japanese quail infected with JM strain of Marek's disease herpesvirus.", "content": "Japanese quail were inoculated with Marek's disease herpesvirus at 1 day of age, and a second group of the same age was infected by contact with inoculated quail. A third group raised in our laboratory as a source of hatching eggs was accidentally infected with Marek's disease (MD). All quail were observed and examined for periods up to 360 days; the usual clinical signs of MD were not observed. However, the birds were susceptible to MD infection because of the evidence that: 1) The MD-specific agar gel-preceipitation (AGP) antigen was found in the feather tips or feather follicular epithelium of some of them; 2) the MD-specific AGP antibody was found in 6 of 57 exposed to MD; and 3) the virus was recovered from 4 MD-exposed birds by subpassage of their kidney cultures into quail embryo fibroblasts. The specificity of the AGP antigen or antibody in MD-infected quail was examined by the line of identity and cross-absorption tests. The antigen specificity was tested against similar to 700 sera from chickens and quail. Although most of these sera reacted with quail-positive antigen (QPA) prepared from MD-infected quail, some sera from infected or uninfected normal chickens reacted nonspecifically with QPA and with an antigen prepared from normal quail. By gel filtration on Sephadex G-150, the specific antigenic component could be separated from the nonspecific component(s) in QPA.", "contents": "Pathogenic and serologic studies of Japanese quail infected with JM strain of Marek's disease herpesvirus. Japanese quail were inoculated with Marek's disease herpesvirus at 1 day of age, and a second group of the same age was infected by contact with inoculated quail. A third group raised in our laboratory as a source of hatching eggs was accidentally infected with Marek's disease (MD). All quail were observed and examined for periods up to 360 days; the usual clinical signs of MD were not observed. However, the birds were susceptible to MD infection because of the evidence that: 1) The MD-specific agar gel-preceipitation (AGP) antigen was found in the feather tips or feather follicular epithelium of some of them; 2) the MD-specific AGP antibody was found in 6 of 57 exposed to MD; and 3) the virus was recovered from 4 MD-exposed birds by subpassage of their kidney cultures into quail embryo fibroblasts. The specificity of the AGP antigen or antibody in MD-infected quail was examined by the line of identity and cross-absorption tests. The antigen specificity was tested against similar to 700 sera from chickens and quail. Although most of these sera reacted with quail-positive antigen (QPA) prepared from MD-infected quail, some sera from infected or uninfected normal chickens reacted nonspecifically with QPA and with an antigen prepared from normal quail. By gel filtration on Sephadex G-150, the specific antigenic component could be separated from the nonspecific component(s) in QPA."} {"id": "PMID:164561", "title": "Studies of FBJ osteosarcoma virus in tissue culture. II. Autoinhibition of focus formation.", "content": "A high-titered non-focus-forming virus, FBJ-MuLV (murine leukemia virus), present in FBJ tumor preparations, inhibited significantly the expression and production of FBJ-MuSV (murine sarcoma virus) in tissue culture. This \"autoinhibition\" was comparable to that observed when a 3- to 4-log excess of infectious MuLV was added to standard MuSV. The degree of inhibition was influenced by the tropism of the MuLV (or the ease of spread and propagation of MuLV in certain cells), multiplicity of infection by MuLV, amount of excess MuLV, and ability of the MuSV-transformed cells to replicate independently. The FBJ MuLV-MuSV complex may be a model system for the detection of sarcoma viruses in spontaneous tumors in various animals where inhibition by excess nontransforming virus could be an important biologic phenomenon.", "contents": "Studies of FBJ osteosarcoma virus in tissue culture. II. Autoinhibition of focus formation. A high-titered non-focus-forming virus, FBJ-MuLV (murine leukemia virus), present in FBJ tumor preparations, inhibited significantly the expression and production of FBJ-MuSV (murine sarcoma virus) in tissue culture. This \"autoinhibition\" was comparable to that observed when a 3- to 4-log excess of infectious MuLV was added to standard MuSV. The degree of inhibition was influenced by the tropism of the MuLV (or the ease of spread and propagation of MuLV in certain cells), multiplicity of infection by MuLV, amount of excess MuLV, and ability of the MuSV-transformed cells to replicate independently. The FBJ MuLV-MuSV complex may be a model system for the detection of sarcoma viruses in spontaneous tumors in various animals where inhibition by excess nontransforming virus could be an important biologic phenomenon."} {"id": "PMID:164562", "title": "Feline oncornavirus-associated cell membrane antigen. II. Antibody titers in healthy cats from household and laboratory colony environments.", "content": "Antibody titers to the feline oncornavirusassociated cell membrane antigen (FOCMA) were determined for 447 healthy cats from laboratory colony and household environments. Only 2.7 percent of 221 cats from colony environments were antibody positive as compared to 50.4 percent of 256 cats from household environments. Incidence of FOCMA antibody and geometric mean antibody titer for pet cats from New York City representing single cat apartment habitats were substantially lower than values for unscreened cats from the Boston, Glasgow, and Detroit suburban environments. Geometric mean antibody titer for young adults in the Boston population was significantly higher than titers for kittens or aged cats. This may be due to greater mobility resulting in increased exposure to other cats. In contrast to the high frequency of FOCMA antibody positivity in pet-cat populations, less than 2 percent of the same groups were positive for virus group-specific antigen in peripheral blood leukocytes and platelets. This was interpreted as an indication that many more cats became infected with feline leukemia virus under natural conditions that the number developing persistent virus infection and/or clinical leukemia.", "contents": "Feline oncornavirus-associated cell membrane antigen. II. Antibody titers in healthy cats from household and laboratory colony environments. Antibody titers to the feline oncornavirusassociated cell membrane antigen (FOCMA) were determined for 447 healthy cats from laboratory colony and household environments. Only 2.7 percent of 221 cats from colony environments were antibody positive as compared to 50.4 percent of 256 cats from household environments. Incidence of FOCMA antibody and geometric mean antibody titer for pet cats from New York City representing single cat apartment habitats were substantially lower than values for unscreened cats from the Boston, Glasgow, and Detroit suburban environments. Geometric mean antibody titer for young adults in the Boston population was significantly higher than titers for kittens or aged cats. This may be due to greater mobility resulting in increased exposure to other cats. In contrast to the high frequency of FOCMA antibody positivity in pet-cat populations, less than 2 percent of the same groups were positive for virus group-specific antigen in peripheral blood leukocytes and platelets. This was interpreted as an indication that many more cats became infected with feline leukemia virus under natural conditions that the number developing persistent virus infection and/or clinical leukemia."} {"id": "PMID:164563", "title": "Feline oncornavirus-associated cell membrane antigen. III. Antibody titers in cats from leukemia cluster households.", "content": "Serum samples from 182 healthy cats residing in environments known to have a natural exposure to feline leukemia virus (FeLV) were examined for the presence of antibody to the feline oncornavirus-associated cell membrane antigen. The number included 138 cats from leukemia-\"cluster\" households. Such cats previously showed greatly increased frequencies of FeLV infection, as determined by the virus group-specific antigen (gasa) in peripheral blood leukocytes and platelets. The geometric mean antibody titer for all 182 cats with known exposure to FeLV was 4.69, more than four times higher than the mean titer for healthy pet cats from the same geographic areas but with no known FeLV exposure. About 92 percent of the cats in exposure environments were positive for FeLV gsa or feline oncornavirus-associated cell membrane antigen (FOCMA) antibody, and gsa-positive cats had lower FOCMA antibody geometric mean titers than gsa-negative cats. In the exposure environments, no differences were seen for cats of different sexes, but a higher geometric mean antibody titer was observed for cats 5 years and over when compared to younger groups. These results prove that previous reports of increased incidences of leukemia in cluster households were not due to chance alone, but rather to increased infection rates of cats in the FeLV environment. Also, they suggest that horizontal transmission of FeLV is highly efficient under crowded conditions, and that most cats naturally exposed to virus elicit an active immune response.", "contents": "Feline oncornavirus-associated cell membrane antigen. III. Antibody titers in cats from leukemia cluster households. Serum samples from 182 healthy cats residing in environments known to have a natural exposure to feline leukemia virus (FeLV) were examined for the presence of antibody to the feline oncornavirus-associated cell membrane antigen. The number included 138 cats from leukemia-\"cluster\" households. Such cats previously showed greatly increased frequencies of FeLV infection, as determined by the virus group-specific antigen (gasa) in peripheral blood leukocytes and platelets. The geometric mean antibody titer for all 182 cats with known exposure to FeLV was 4.69, more than four times higher than the mean titer for healthy pet cats from the same geographic areas but with no known FeLV exposure. About 92 percent of the cats in exposure environments were positive for FeLV gsa or feline oncornavirus-associated cell membrane antigen (FOCMA) antibody, and gsa-positive cats had lower FOCMA antibody geometric mean titers than gsa-negative cats. In the exposure environments, no differences were seen for cats of different sexes, but a higher geometric mean antibody titer was observed for cats 5 years and over when compared to younger groups. These results prove that previous reports of increased incidences of leukemia in cluster households were not due to chance alone, but rather to increased infection rates of cats in the FeLV environment. Also, they suggest that horizontal transmission of FeLV is highly efficient under crowded conditions, and that most cats naturally exposed to virus elicit an active immune response."} {"id": "PMID:164564", "title": "Infection of capuchin monkeys (Cebus albifrons) with Herpesvirus saimiri.", "content": "Herpesvirus saimiri (HVS) induced persistent, clinically inapparent infections of long-term duration in capuchin monkeys (Cebus albifrons). The infections were characterized by development of antibody to HVS-associated antigens and recovery of low levels of virus-genome-carrying lymphocytes in the peripheral blood. Peripheral lymphocyte counts remained in low-normal to normal ranges and no physical signs of lymphoma were evident. Prednisolone treatment caused immunosuppression in one monkey; this was accompanied by a progressive loss of humoral antibody to HVS-associated antigens, but neoplastic disease did not develop.", "contents": "Infection of capuchin monkeys (Cebus albifrons) with Herpesvirus saimiri. Herpesvirus saimiri (HVS) induced persistent, clinically inapparent infections of long-term duration in capuchin monkeys (Cebus albifrons). The infections were characterized by development of antibody to HVS-associated antigens and recovery of low levels of virus-genome-carrying lymphocytes in the peripheral blood. Peripheral lymphocyte counts remained in low-normal to normal ranges and no physical signs of lymphoma were evident. Prednisolone treatment caused immunosuppression in one monkey; this was accompanied by a progressive loss of humoral antibody to HVS-associated antigens, but neoplastic disease did not develop."} {"id": "PMID:164565", "title": "Depression in lymphocyte response to general mitogens by owl monkeys infected with Herpesvirus saimiri.", "content": "The effect of Herpesvirus saimiri (HVS) infection on the response of owl monkey lymphocytes to general mitogens was examined during the development of neoplastic disease. The reactivity of the lymphocytes was then correlated with the clinical condition of the infected monkeys and the content of virus rescued from the peripheral blood lymphocytes (PBL). Eight monkeys developed lymphoma which, in six monkeys, was accompanied by lymphocytic leukemia. All animals that died of HVS-induced neoplasia consistently showed a lack of mitogenic response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen, while always reduced, was generally less markedly affected than the response to the other two mitogens. Lymphocytes from five of the leukemic animals demonstrated an elevated level of spontaneous DNA synthesis in culture late in the disease. This increased spontaneous DNA synthesis tended to correlate with the rescue of HVS from the PBL as demonstrated by the infective center assay. Although mitogenic hyporesponsiveness corresponded with HVS rescue from PBL in six of nine monkeys, the impairment of normal lymphocyte responsiveness sometimes preceded virus recovery.", "contents": "Depression in lymphocyte response to general mitogens by owl monkeys infected with Herpesvirus saimiri. The effect of Herpesvirus saimiri (HVS) infection on the response of owl monkey lymphocytes to general mitogens was examined during the development of neoplastic disease. The reactivity of the lymphocytes was then correlated with the clinical condition of the infected monkeys and the content of virus rescued from the peripheral blood lymphocytes (PBL). Eight monkeys developed lymphoma which, in six monkeys, was accompanied by lymphocytic leukemia. All animals that died of HVS-induced neoplasia consistently showed a lack of mitogenic response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen, while always reduced, was generally less markedly affected than the response to the other two mitogens. Lymphocytes from five of the leukemic animals demonstrated an elevated level of spontaneous DNA synthesis in culture late in the disease. This increased spontaneous DNA synthesis tended to correlate with the rescue of HVS from the PBL as demonstrated by the infective center assay. Although mitogenic hyporesponsiveness corresponded with HVS rescue from PBL in six of nine monkeys, the impairment of normal lymphocyte responsiveness sometimes preceded virus recovery."} {"id": "PMID:164566", "title": "Effect of bacillus Calmette-Gu\u00e9rin immunization in marmosets infected experimentally with Herpesvirus saimiri.", "content": "Eight white-lipped marmosets immunized with BCG and 3 sham-immunized marmosets were studied after inoculation with Herpesvirus saimiri (HVS). BCG immunization had no significant influence on the incidence of infection by HVS, incidence of fatal malignant lymphoma, time of leukemia onset, development or titer of HVS antibodies, or average survival time. One BCG-immunized, HVS-infected marmoset failed to develop malignant lymphoma, whereas the remaining 10 HVS-infected marmosets died of malignant lymphoma. Prolonged survival occurred also in 1 marmoset immunized with BCG 100 days after HVS inoculation. The development and disappearance of lymphocyte reactivity to tuberculin were followed in 4 BCG-immunized marmosets.", "contents": "Effect of bacillus Calmette-Gu\u00e9rin immunization in marmosets infected experimentally with Herpesvirus saimiri. Eight white-lipped marmosets immunized with BCG and 3 sham-immunized marmosets were studied after inoculation with Herpesvirus saimiri (HVS). BCG immunization had no significant influence on the incidence of infection by HVS, incidence of fatal malignant lymphoma, time of leukemia onset, development or titer of HVS antibodies, or average survival time. One BCG-immunized, HVS-infected marmoset failed to develop malignant lymphoma, whereas the remaining 10 HVS-infected marmosets died of malignant lymphoma. Prolonged survival occurred also in 1 marmoset immunized with BCG 100 days after HVS inoculation. The development and disappearance of lymphocyte reactivity to tuberculin were followed in 4 BCG-immunized marmosets."} {"id": "PMID:164567", "title": "Virus expression and immunoprophylaxis of a murine lymphoma.", "content": "CBA mice tested with a rapidly lethal transplanted lymphoma could survive challenge when pretreated with allogeneic lymphoma cells or other material expressing murine leukemia virus (MuLV). Protection resulted when recipients were given injections of AKR and C3H transplanted lymphomas or selected normal AKR and SJL tissues, filtrates of which give positive assays for MuLV by in vitro and/or in vivo tests. There was no protection when recipients were given injections of C3H lymphomas or C3H normal tissues that failed to have positive assays for virus.", "contents": "Virus expression and immunoprophylaxis of a murine lymphoma. CBA mice tested with a rapidly lethal transplanted lymphoma could survive challenge when pretreated with allogeneic lymphoma cells or other material expressing murine leukemia virus (MuLV). Protection resulted when recipients were given injections of AKR and C3H transplanted lymphomas or selected normal AKR and SJL tissues, filtrates of which give positive assays for MuLV by in vitro and/or in vivo tests. There was no protection when recipients were given injections of C3H lymphomas or C3H normal tissues that failed to have positive assays for virus."} {"id": "PMID:164568", "title": "Antitumor activity of bacterial infection. II. effect of Listeria monocytogenes on growth of a guinea pig hepatoma.", "content": "Growth of a guinea pig hepatoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal (id) injection into syngeneic recipients. Heat-killed LM were less effective than viable organisms in suppressing tumor growth. A vaccine containing oil droplets and LM cell walls lacked antitumor activity. Intratumor injection of viable LM on the 7th day after id injection of tumor cells prolonged survival of guinea pigs that did not succumb to LM infection. After intratumor injection of 0.6 times 10-8-1.0 times 10-8 LM, 5 of 22 guinea pigs died from acute infection (23 percent). In the 17 survivors, 3 tumors regressed completely (18 percent). Animals surviving injections of LM and tumor cells were immune to a second challenge with tumor cells. Immunization ofguinea pigs with an intravenous injection of LM decreased the mortality from intratumor injection of LM, but the intratumor injection of LM failed to cure a significant fraction of LM-immune animals bearing 7-day hepatoma transplants. BCG was more effective than LM in producing tumor regression. Synergism between LM and BCG was not observed, and simultaneous intratumor injection of BCG and LM was no more effective than intratumor injection of BCG alone in the treatment of 12-day tumor transplants.", "contents": "Antitumor activity of bacterial infection. II. effect of Listeria monocytogenes on growth of a guinea pig hepatoma. Growth of a guinea pig hepatoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal (id) injection into syngeneic recipients. Heat-killed LM were less effective than viable organisms in suppressing tumor growth. A vaccine containing oil droplets and LM cell walls lacked antitumor activity. Intratumor injection of viable LM on the 7th day after id injection of tumor cells prolonged survival of guinea pigs that did not succumb to LM infection. After intratumor injection of 0.6 times 10-8-1.0 times 10-8 LM, 5 of 22 guinea pigs died from acute infection (23 percent). In the 17 survivors, 3 tumors regressed completely (18 percent). Animals surviving injections of LM and tumor cells were immune to a second challenge with tumor cells. Immunization ofguinea pigs with an intravenous injection of LM decreased the mortality from intratumor injection of LM, but the intratumor injection of LM failed to cure a significant fraction of LM-immune animals bearing 7-day hepatoma transplants. BCG was more effective than LM in producing tumor regression. Synergism between LM and BCG was not observed, and simultaneous intratumor injection of BCG and LM was no more effective than intratumor injection of BCG alone in the treatment of 12-day tumor transplants."} {"id": "PMID:164569", "title": "Aberrant viruses in cells infected with murine sarcoma virus-feline leukemia virus.", "content": "This study describes an unusual type of virus seen when a feline leukemia virus (FeLV) pseudotype of murine sarcoma virus (MuSV) obtained by cocentrifugation procedures infected feline embryo cells (FEF) and two Crandell cat cell lines (CrFK1, CrFK2). When all three cell cultures were infected with MuSV-FeLV, only FEF and CrFK2 were transformed and only these showed normal and aberrant virus. The CrFK1 infected with MuSV-FeLV did not transform but did replicate normal type-C virus with a 50-A intermediate coat. The virus replicated in the two transformed lines showed three particles; a normal particle with a 50-A intermediate coat, a normal particle with a 100-A intermediate coat, and an aberrant particle with a 100-A intermediate coat.", "contents": "Aberrant viruses in cells infected with murine sarcoma virus-feline leukemia virus. This study describes an unusual type of virus seen when a feline leukemia virus (FeLV) pseudotype of murine sarcoma virus (MuSV) obtained by cocentrifugation procedures infected feline embryo cells (FEF) and two Crandell cat cell lines (CrFK1, CrFK2). When all three cell cultures were infected with MuSV-FeLV, only FEF and CrFK2 were transformed and only these showed normal and aberrant virus. The CrFK1 infected with MuSV-FeLV did not transform but did replicate normal type-C virus with a 50-A intermediate coat. The virus replicated in the two transformed lines showed three particles; a normal particle with a 50-A intermediate coat, a normal particle with a 100-A intermediate coat, and an aberrant particle with a 100-A intermediate coat."} {"id": "PMID:164570", "title": "Moloney sarcoma virus-induced tumors in athymic (nude) mice: growth pattern and antibody responses.", "content": "Tumor growth and antibody production were evaluated in nude (nu/nu) mice and their heterozygous normal (+/nu) littermates after inoculation of Moloney sarcoma virus (MSV). Sarcoma-bearing nude mice developed progressively growing tumors, whereas 53 percent of their normal counterparts showed tumor regressions. By indirect membrane fluorescence, significant amounts of IgG antibody to MSV could be detected in thymus-bearing but not in nude mice.", "contents": "Moloney sarcoma virus-induced tumors in athymic (nude) mice: growth pattern and antibody responses. Tumor growth and antibody production were evaluated in nude (nu/nu) mice and their heterozygous normal (+/nu) littermates after inoculation of Moloney sarcoma virus (MSV). Sarcoma-bearing nude mice developed progressively growing tumors, whereas 53 percent of their normal counterparts showed tumor regressions. By indirect membrane fluorescence, significant amounts of IgG antibody to MSV could be detected in thymus-bearing but not in nude mice."} {"id": "PMID:164576", "title": "Intercurrent cytomegalovirus colitis in a patient with ulcerative colitis.", "content": "Acute intercurrent CMV colitis developed in a patient with UC who was receiving prednisone. CMV infection was suggested by light and electron microscopic study of a rectal biopsy taken during the acute episode and was confirmed by serology done nine months later. The microscopic studies of plastic-embedded tissues demonstrated that infected cells were concentrated in a subendothelial location and were presumably macrophages. Epithelial and endothelial cells were not involved. Steroid therapy and the inflammation and repair process (granulartion tissue) of active UC may have predisposed the present patient to CMV colitis. CMV infection has been reported to be more common in patients with UC than in the general population. Detection of CMV colitis in patients with UC could be of special importance since alteration of immunosuppressive therapy may be indicated.", "contents": "Intercurrent cytomegalovirus colitis in a patient with ulcerative colitis. Acute intercurrent CMV colitis developed in a patient with UC who was receiving prednisone. CMV infection was suggested by light and electron microscopic study of a rectal biopsy taken during the acute episode and was confirmed by serology done nine months later. The microscopic studies of plastic-embedded tissues demonstrated that infected cells were concentrated in a subendothelial location and were presumably macrophages. Epithelial and endothelial cells were not involved. Steroid therapy and the inflammation and repair process (granulartion tissue) of active UC may have predisposed the present patient to CMV colitis. CMV infection has been reported to be more common in patients with UC than in the general population. Detection of CMV colitis in patients with UC could be of special importance since alteration of immunosuppressive therapy may be indicated."} {"id": "PMID:164578", "title": "Renal action of cholera toxin: II. Effects on adenylate cyclase-cyclic AMP system.", "content": "The effects of cholera toxin (CT) on the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) system(s) in renal cortex were examined using the isolated renal cortical tubules of rat. Unlike parathyroid hormone, catecholamines or prostaglandins, CT had no immediate effects on cAMP production by the tubules or on adenylate cyclase activity. However, after 30 min of incubation at 37 C, cAMP production by the tubules started to rise and reached a plateau between 60 and 90 min. This rise in cAMP production was not abolished by protein synthesis inhibitors (actinomycin D and cycloheximide) nor by the inhibitors of prostaglandin synthesis (acetyl-salicylate and indomethacin). Repeated washings of the tubules exposed to the toxin for five minutes at 0 or 37 C did not abolish the effect of CT to stimulate cAMP production. Assays of adenylate cyclase activity using homogenates prepared from isolated tubules which were incubated for 60 min with CT revealed an increase in the basal adenylate cyclase activity without any change in NaF-sensitive enzyme activity. It is concluded that CT binds to renal tubule cells rapidly, possibly through energy-independent process. CT stimulates adenylate cyclase activity and increases cAMP production by the renal tubule cells after a latent period of 30 min. The stimulatory effects of CT are not due to new protein synthesis or prostaglandin formation.", "contents": "Renal action of cholera toxin: II. Effects on adenylate cyclase-cyclic AMP system. The effects of cholera toxin (CT) on the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) system(s) in renal cortex were examined using the isolated renal cortical tubules of rat. Unlike parathyroid hormone, catecholamines or prostaglandins, CT had no immediate effects on cAMP production by the tubules or on adenylate cyclase activity. However, after 30 min of incubation at 37 C, cAMP production by the tubules started to rise and reached a plateau between 60 and 90 min. This rise in cAMP production was not abolished by protein synthesis inhibitors (actinomycin D and cycloheximide) nor by the inhibitors of prostaglandin synthesis (acetyl-salicylate and indomethacin). Repeated washings of the tubules exposed to the toxin for five minutes at 0 or 37 C did not abolish the effect of CT to stimulate cAMP production. Assays of adenylate cyclase activity using homogenates prepared from isolated tubules which were incubated for 60 min with CT revealed an increase in the basal adenylate cyclase activity without any change in NaF-sensitive enzyme activity. It is concluded that CT binds to renal tubule cells rapidly, possibly through energy-independent process. CT stimulates adenylate cyclase activity and increases cAMP production by the renal tubule cells after a latent period of 30 min. The stimulatory effects of CT are not due to new protein synthesis or prostaglandin formation."} {"id": "PMID:164579", "title": "Effect of hypotonicity on cyclic adenosine monophosphate formation and action in vasopressin target cells.", "content": "We have shown previously that overhydration of toads renders their urinary bladders less responsive to the antidiuretic action of vasopressin (AVP). The present study investigates the relationship between osmotic swelling of vasopressin target cells and their sensitivity to AVP and dibutyryl cyclic adenosine monophosphate (db-cAMP). Conditions which engender osmotic swelling of toad bladder epithelial cells, such as immersing bladders on both surfaces in hypotonic Ringer's fluid or subjecting them to a net mucosal-to-serosal volume flux, markedly inhibited the effectiveness of db-cAMP in raising bladder permeability to water. This inhibitory phenomenon was seen both with serosal and mucosal applications of the nucleotide. Examination of isolated epithelial cells by phase contrast microscopy showed them to behave as osmometers, doubling their volume as the effective osmolality of the incubation medium was halved. AVP was found to increase the total content of cAMP about 3.5-fold both in the swollen and the normal cells, so that the actual concentration of cAMP may have diminished as the cell volume increased. Consistent with this suggestion was the observation that increasing exogenous db-cAMP abolished, in part, the inhibitory effects of hypotonicity. These observations indicate that homeostasis of body fluids in the toad depends in part upon the osmotic regulation of anti-diuretic homone action, and that intracellular cAMP may participate in coupling changes in cell volume to the altered state of responsiveness of the vasopressin target cell.", "contents": "Effect of hypotonicity on cyclic adenosine monophosphate formation and action in vasopressin target cells. We have shown previously that overhydration of toads renders their urinary bladders less responsive to the antidiuretic action of vasopressin (AVP). The present study investigates the relationship between osmotic swelling of vasopressin target cells and their sensitivity to AVP and dibutyryl cyclic adenosine monophosphate (db-cAMP). Conditions which engender osmotic swelling of toad bladder epithelial cells, such as immersing bladders on both surfaces in hypotonic Ringer's fluid or subjecting them to a net mucosal-to-serosal volume flux, markedly inhibited the effectiveness of db-cAMP in raising bladder permeability to water. This inhibitory phenomenon was seen both with serosal and mucosal applications of the nucleotide. Examination of isolated epithelial cells by phase contrast microscopy showed them to behave as osmometers, doubling their volume as the effective osmolality of the incubation medium was halved. AVP was found to increase the total content of cAMP about 3.5-fold both in the swollen and the normal cells, so that the actual concentration of cAMP may have diminished as the cell volume increased. Consistent with this suggestion was the observation that increasing exogenous db-cAMP abolished, in part, the inhibitory effects of hypotonicity. These observations indicate that homeostasis of body fluids in the toad depends in part upon the osmotic regulation of anti-diuretic homone action, and that intracellular cAMP may participate in coupling changes in cell volume to the altered state of responsiveness of the vasopressin target cell."} {"id": "PMID:164581", "title": "[Age-dependent biochemical studies on the extrarenal effect of furosemid (author's transl)].", "content": "The present study investigated the activities of lysosomal enzymes of the liver after administration of Furosemid. 10 weeks and 1-year old male albino rats were treated with 40 mg Furosemid for 4 subsequent days. According to the method devised by de Duve a sediment rich in lysosomes was produced by fractionated centrifugation and subsequently the enzyme activity of beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D and a collagenolytic enzyme was measured in the sediment as well as in the corresponding lysosomal supernatant. The protein content served as a reference for the enzyme activities. In addition, we investigated the activities of cytoplasmic enzymes such as GOT, GPT, gamma-GT and the alkaline phosphatase. The enzyme activity changes were age-dependent. With Furosemid treatment the activities of beta-glucuronidase and cathepsin D increased in the lysosomal supernatant and the lysosomal sediment of the 1-year old rats, whereas the activities of the collagenolytic enzyme increased in the lysosomal sediment of the same group. In the lysosomal sediment of the 10-weeks old rats a decrease of beta-glucuronidase, beta-acetylglucosaminidase and cathepsin D was observed. These results are discussed in the light of reports from the literature.", "contents": "[Age-dependent biochemical studies on the extrarenal effect of furosemid (author's transl)]. The present study investigated the activities of lysosomal enzymes of the liver after administration of Furosemid. 10 weeks and 1-year old male albino rats were treated with 40 mg Furosemid for 4 subsequent days. According to the method devised by de Duve a sediment rich in lysosomes was produced by fractionated centrifugation and subsequently the enzyme activity of beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D and a collagenolytic enzyme was measured in the sediment as well as in the corresponding lysosomal supernatant. The protein content served as a reference for the enzyme activities. In addition, we investigated the activities of cytoplasmic enzymes such as GOT, GPT, gamma-GT and the alkaline phosphatase. The enzyme activity changes were age-dependent. With Furosemid treatment the activities of beta-glucuronidase and cathepsin D increased in the lysosomal supernatant and the lysosomal sediment of the 1-year old rats, whereas the activities of the collagenolytic enzyme increased in the lysosomal sediment of the same group. In the lysosomal sediment of the 10-weeks old rats a decrease of beta-glucuronidase, beta-acetylglucosaminidase and cathepsin D was observed. These results are discussed in the light of reports from the literature."} {"id": "PMID:164580", "title": "[Carcinofetal antigens. I. alpha-fetoprotein (author's transl)].", "content": "Alpha-fetoprotein (AFP) is an alpha1-glycoprotein (M.W. about 65000) appearing in the fetal serum of most mammals including man during the early stages of pregnancy; 4 weeks after birth it disappears altogether or exists at very low concentrations as in the normal adult. AFP is formed in the yolk sac, the fetal liver and the gastro-intestinal tract. One of its physiological functions in fetal life is supposed to be the protection of the fetus from maternal oestrogens (oestrophilic property). The clinical significance of AFP is based on the regular and increasing production in primary liver cell carcinoma, less frequently in teratogenetic tumors where it serves as a control of therapy and course of the disease. Less frequent, minor and temporary increases in the AFP serum level occur in several primary tumors with secondary liver involvement, and in inflammatory gastro-intestinal diseases, e.g. of the liver (hepatitis, cirrhosis). AFP has an increasing importance in gynecology (gestational age, fetal distress syndrom, malformations, hydatidiform mole/chorion carcinoma). The physico-chemical properties of AFP are widely known. Both fetal and tumor AFP appear to be immunologically and biochemically identical, as are that of tissue and biological fluids. The differences observed (variants, microheterogeneity) depend mainly on the different content of sialic acid. An antigenetic relationship exists, between the AFP of most species. The immunodiffusion (Ouchterlony) is the most frequently used but relatively insensitive test (1-5 mug/ml) in finding AFP, whereas the radioimmunoassay is the most sensitive one (up to 0,25 ng/ml) and permits the determination of normal serum levels in adults (below 20 ng/ml). The serum concentration in healthy pregnant women lies up to 500 ng/ml, in patients with hepatitis, liver cirrhosis and other liver diseases mostly under 3 mug/ml, whereas in those with primary liver cell carcinoma levels up to and above 600 mg-percent have been found.", "contents": "[Carcinofetal antigens. I. alpha-fetoprotein (author's transl)]. Alpha-fetoprotein (AFP) is an alpha1-glycoprotein (M.W. about 65000) appearing in the fetal serum of most mammals including man during the early stages of pregnancy; 4 weeks after birth it disappears altogether or exists at very low concentrations as in the normal adult. AFP is formed in the yolk sac, the fetal liver and the gastro-intestinal tract. One of its physiological functions in fetal life is supposed to be the protection of the fetus from maternal oestrogens (oestrophilic property). The clinical significance of AFP is based on the regular and increasing production in primary liver cell carcinoma, less frequently in teratogenetic tumors where it serves as a control of therapy and course of the disease. Less frequent, minor and temporary increases in the AFP serum level occur in several primary tumors with secondary liver involvement, and in inflammatory gastro-intestinal diseases, e.g. of the liver (hepatitis, cirrhosis). AFP has an increasing importance in gynecology (gestational age, fetal distress syndrom, malformations, hydatidiform mole/chorion carcinoma). The physico-chemical properties of AFP are widely known. Both fetal and tumor AFP appear to be immunologically and biochemically identical, as are that of tissue and biological fluids. The differences observed (variants, microheterogeneity) depend mainly on the different content of sialic acid. An antigenetic relationship exists, between the AFP of most species. The immunodiffusion (Ouchterlony) is the most frequently used but relatively insensitive test (1-5 mug/ml) in finding AFP, whereas the radioimmunoassay is the most sensitive one (up to 0,25 ng/ml) and permits the determination of normal serum levels in adults (below 20 ng/ml). The serum concentration in healthy pregnant women lies up to 500 ng/ml, in patients with hepatitis, liver cirrhosis and other liver diseases mostly under 3 mug/ml, whereas in those with primary liver cell carcinoma levels up to and above 600 mg-percent have been found."} {"id": "PMID:164582", "title": "[Gas exchange and blood indices in thyroid gland dysfunction].", "content": "An exposure of intact rats to a hyperoxic atmosphere of 2 atm for one hour a day during 20 days induced no changes in the gas exchange or hemoglobin and red blood cells content. The concentration of free radicals tended to decline. Thyroidectomized rats kept in a normoxic atmosphere showed anemia and gas exchange decrease. The concentration of free radicals in the tissues declined slightly. These parameters returned to the norm after the hyperoxybaric exposure. During a normoxic exposure thyroxine injections accelerated gas exchange, producing no significant changes in the red blood composition. The free-radical activity tended to increase. After a hyperoxybaric exposure similar changes took place.", "contents": "[Gas exchange and blood indices in thyroid gland dysfunction]. An exposure of intact rats to a hyperoxic atmosphere of 2 atm for one hour a day during 20 days induced no changes in the gas exchange or hemoglobin and red blood cells content. The concentration of free radicals tended to decline. Thyroidectomized rats kept in a normoxic atmosphere showed anemia and gas exchange decrease. The concentration of free radicals in the tissues declined slightly. These parameters returned to the norm after the hyperoxybaric exposure. During a normoxic exposure thyroxine injections accelerated gas exchange, producing no significant changes in the red blood composition. The free-radical activity tended to increase. After a hyperoxybaric exposure similar changes took place."} {"id": "PMID:164589", "title": "Short term culture of dissociated rat submandibular gland cells.", "content": "Submandibular glands of 4-week-old rats were dissociated by a procedure involving digestions with collagenase and hyaluronidase, chelation with ethylenediaminetetraacetic acid, and mechanical force. The isolated cells were purified by centrifugation in a Ficoli solution and were maintained in culture for 36 hours. On the basis of trypan blue exclusions, about 70 per cent of the dissociated cells were viable. Electron microscopic observations indicated that the isolated acinar cells and intercalated and striated duct cells retained their essential in situ ultrastructural characteristics. During a 36-hour culture period the number of viable cells declined to about 40 per cent, and the various cell types formed mixed aggregates. The ultrastructural features of the intercalated and duct cells changed relatively little, but the acinar cells revealed several structural alterations. These included a decrease in the number of the secretory granules, fusions of the secretory granules, and an increase in the rough surfaced endoplasmic reticulum. In general, the polarity of acinar cells became less distinct. The endogenous peroxidase activity in the acinar cells gradually diminished during the culture. Isoproterenol when added to the cultured cells failed to stimulate the incorporation of radioactive thymidine or the discharge of the secretory material from the acinar cells.", "contents": "Short term culture of dissociated rat submandibular gland cells. Submandibular glands of 4-week-old rats were dissociated by a procedure involving digestions with collagenase and hyaluronidase, chelation with ethylenediaminetetraacetic acid, and mechanical force. The isolated cells were purified by centrifugation in a Ficoli solution and were maintained in culture for 36 hours. On the basis of trypan blue exclusions, about 70 per cent of the dissociated cells were viable. Electron microscopic observations indicated that the isolated acinar cells and intercalated and striated duct cells retained their essential in situ ultrastructural characteristics. During a 36-hour culture period the number of viable cells declined to about 40 per cent, and the various cell types formed mixed aggregates. The ultrastructural features of the intercalated and duct cells changed relatively little, but the acinar cells revealed several structural alterations. These included a decrease in the number of the secretory granules, fusions of the secretory granules, and an increase in the rough surfaced endoplasmic reticulum. In general, the polarity of acinar cells became less distinct. The endogenous peroxidase activity in the acinar cells gradually diminished during the culture. Isoproterenol when added to the cultured cells failed to stimulate the incorporation of radioactive thymidine or the discharge of the secretory material from the acinar cells."} {"id": "PMID:164590", "title": "Dissociation of rat parotid gland.", "content": "Rat parotid gland was dissociated by sequential collagenase and hyaluronidase digestions, chelation with ethylenediaminetetraacetic acid, and mild shearing force to yield predominantly single cells. The isolated acinar cells retained their morphologic characteristics and their amylase activity. The functional integrity of the isolated cells was assessed by measuring their secretory response to isoproterenol, epinephrine, and carbamylcholine and by their ability to incorporate radioactively labeled leucine and thymidine. The discharge of amylase from the dissociated cells was not effected by isoproterenol or norepinephrine and the response to carbamylcholine was minimal. The data indicate a destruction or perturbation of hormone receptors during the dissociation procedure. The maintenance of the cells in culture for up to 18 hours failed to restore the responsiveness of the isolated parotid gland acinar cells to isoproterenol. The isolated cells incorporated 14C-leucine into proteins at a linear rate between 30 and 180 minutes. Chromatographic and electrophoretic profiles of newly synthesized proteins indicated that all major proteins synthesized in vivo were also synthesized by the isolated cells. The isolated cells incorporated tritiated thymidine into DNA. Furthermore, stimulation of DNA synthesis by isoproterenol in vivo was reflected by a higher rate of thymidine incorporation by the isolated cells as compared with controls. The dissociated parotid gland cells offer a convenient system for studying various cellular processes, particularly the synthesis of macromolecules with high specific activity. However, some functions, notably the response to beta- adrenergic agonists, are lost during the dissociation procedure.", "contents": "Dissociation of rat parotid gland. Rat parotid gland was dissociated by sequential collagenase and hyaluronidase digestions, chelation with ethylenediaminetetraacetic acid, and mild shearing force to yield predominantly single cells. The isolated acinar cells retained their morphologic characteristics and their amylase activity. The functional integrity of the isolated cells was assessed by measuring their secretory response to isoproterenol, epinephrine, and carbamylcholine and by their ability to incorporate radioactively labeled leucine and thymidine. The discharge of amylase from the dissociated cells was not effected by isoproterenol or norepinephrine and the response to carbamylcholine was minimal. The data indicate a destruction or perturbation of hormone receptors during the dissociation procedure. The maintenance of the cells in culture for up to 18 hours failed to restore the responsiveness of the isolated parotid gland acinar cells to isoproterenol. The isolated cells incorporated 14C-leucine into proteins at a linear rate between 30 and 180 minutes. Chromatographic and electrophoretic profiles of newly synthesized proteins indicated that all major proteins synthesized in vivo were also synthesized by the isolated cells. The isolated cells incorporated tritiated thymidine into DNA. Furthermore, stimulation of DNA synthesis by isoproterenol in vivo was reflected by a higher rate of thymidine incorporation by the isolated cells as compared with controls. The dissociated parotid gland cells offer a convenient system for studying various cellular processes, particularly the synthesis of macromolecules with high specific activity. However, some functions, notably the response to beta- adrenergic agonists, are lost during the dissociation procedure."} {"id": "PMID:164594", "title": "Viruses: causative agents of cancer.", "content": "Evidence accumulated over a period of 60 years has clearly established that a number of different viruses cause neoplasia (of a broad spectrum) amongst a variety of animals. Although it is known that viruses do produce self-limiting proliferative human diseases, complete verification of a human viral carcinogen remains to be provided. This paper presents an overview of the conceptual and practical tools for the detection of tumor viruses, which have derived from experimental model systems. It indicates how these are being applied to studies of human malignant disease, with special reference to assessing a possible viral etiology for laryngeal cancer.", "contents": "Viruses: causative agents of cancer. Evidence accumulated over a period of 60 years has clearly established that a number of different viruses cause neoplasia (of a broad spectrum) amongst a variety of animals. Although it is known that viruses do produce self-limiting proliferative human diseases, complete verification of a human viral carcinogen remains to be provided. This paper presents an overview of the conceptual and practical tools for the detection of tumor viruses, which have derived from experimental model systems. It indicates how these are being applied to studies of human malignant disease, with special reference to assessing a possible viral etiology for laryngeal cancer."} {"id": "PMID:164599", "title": "Development of hyperbetalipoproteinemia in pigs fed atherogenic diet.", "content": "Hormel miniature pigs were studied over a period of 24 weeks to observe the changes in serum lipoprotein pattern, cholesteryl ester, free cholesterol, and triglyceride in the atherogenic-fed pigs. These pigs were compared to age-related control animals in our breeding herd. Pigs fed the atherogenic diet (20% tallow, 3% cholesterol, and a bile supplement) exhibited a heterogeneous response but showed mean increases in cholesteryl ester (571 mg/dl) and free cholesterol (226 mg/dl), a slight increase in triglyceride (58 mg/dl), and a severe hyperbetalipoproteinemia. Three animals with the highest cholesteryl ester (all above 600 mg/dl) had resolvable beta components in their 1.006 g/ml very low density lipoprotein fraction (type III), as well as huge increases in the Sf 12-20 low density lipoprotein fraction. The other four animals had substantial increases in Sf 0-20, and the three highest had much of their low density lipoprotein in the Sf 12-20, or \"remnant\" fraction. The test pigs all showed gross lesions in the aorta with an increase in cholesteryl ester and free cholesterol in the tissue as compared with control animals.", "contents": "Development of hyperbetalipoproteinemia in pigs fed atherogenic diet. Hormel miniature pigs were studied over a period of 24 weeks to observe the changes in serum lipoprotein pattern, cholesteryl ester, free cholesterol, and triglyceride in the atherogenic-fed pigs. These pigs were compared to age-related control animals in our breeding herd. Pigs fed the atherogenic diet (20% tallow, 3% cholesterol, and a bile supplement) exhibited a heterogeneous response but showed mean increases in cholesteryl ester (571 mg/dl) and free cholesterol (226 mg/dl), a slight increase in triglyceride (58 mg/dl), and a severe hyperbetalipoproteinemia. Three animals with the highest cholesteryl ester (all above 600 mg/dl) had resolvable beta components in their 1.006 g/ml very low density lipoprotein fraction (type III), as well as huge increases in the Sf 12-20 low density lipoprotein fraction. The other four animals had substantial increases in Sf 0-20, and the three highest had much of their low density lipoprotein in the Sf 12-20, or \"remnant\" fraction. The test pigs all showed gross lesions in the aorta with an increase in cholesteryl ester and free cholesterol in the tissue as compared with control animals."} {"id": "PMID:164613", "title": "[The situation of suicide prevention (author's transl)].", "content": "Suicide research has always been especially concerned with the social connections. Its results however have not been sufficiently used for the benefit of suicide prevention. Suicide prevention is linked to a somatically oriented medicine, which is not able to provide with an after care program. To show the present status of practical suicide prevention, an investigation was carried out in Hanover, the result of which postulates for an intesification of social services and psychiatric consulting services; it also demands a support of counseling services by telephone, special information about the possibilities of suicide prevention, and the initiation of suicide prevention centers in big towns, that work with an inter-disciplinary staff.", "contents": "[The situation of suicide prevention (author's transl)]. Suicide research has always been especially concerned with the social connections. Its results however have not been sufficiently used for the benefit of suicide prevention. Suicide prevention is linked to a somatically oriented medicine, which is not able to provide with an after care program. To show the present status of practical suicide prevention, an investigation was carried out in Hanover, the result of which postulates for an intesification of social services and psychiatric consulting services; it also demands a support of counseling services by telephone, special information about the possibilities of suicide prevention, and the initiation of suicide prevention centers in big towns, that work with an inter-disciplinary staff."} {"id": "PMID:164616", "title": "[Synthetic depot-ACTH, plasmacortisol levels, and asthmatic syndrome (author's transl)].", "content": "Plasmacortisol levels were measured in 33 patients with asthmatic syndrome before and after they received treatment with 6 mg of depot-ACTH (Tetracosactid) over seven days. 75 percent of the patients showed improved VC and FEF after therapy. This effect was not in any way correlated to the basal level of cortisol, nor to the increment during treatment.", "contents": "[Synthetic depot-ACTH, plasmacortisol levels, and asthmatic syndrome (author's transl)]. Plasmacortisol levels were measured in 33 patients with asthmatic syndrome before and after they received treatment with 6 mg of depot-ACTH (Tetracosactid) over seven days. 75 percent of the patients showed improved VC and FEF after therapy. This effect was not in any way correlated to the basal level of cortisol, nor to the increment during treatment."} {"id": "PMID:164619", "title": "The mechanism of lipid-binding by plasma lipoproteins.", "content": "In this article, we review the current state of knowledge about the structure of human plasma high density lipoproteins. Recent advances in this field, including amino acid sequencing and lipid-binding studies, suggest that the plasma lipoproteins have specific sites with special structural features that account for their ability to bind and transport lipid. A hypothesis which describes the structure of these lipid-binding sites and their interaction with lipid is presented.", "contents": "The mechanism of lipid-binding by plasma lipoproteins. In this article, we review the current state of knowledge about the structure of human plasma high density lipoproteins. Recent advances in this field, including amino acid sequencing and lipid-binding studies, suggest that the plasma lipoproteins have specific sites with special structural features that account for their ability to bind and transport lipid. A hypothesis which describes the structure of these lipid-binding sites and their interaction with lipid is presented."} {"id": "PMID:164621", "title": "[Results of a nine-year phenylketonuria (PKU) screening (author's transl)].", "content": "The percentage of children in Nordrhein-Westfalen who were tested for PKU free of charge and on a voluntary basis rose from 25.3% (1966) to 99.5% (1973). Among 1,431,999 newly born children, 262 children with suspected PKU were found, 225 of them diagnosed early and 37 late, 181 with \"typical\" and 81 with \"atypical\" PKU. Most of 102 children with late diagnosed PKU had an I.Q. of 80-50 or less, while in 95 children treated early, it was over 91 in 80% and below 90 in only 20%. There was a statistically highly significant difference in the I.Q. distribution between patients diagnosed early and those diagnosed late, while the mental development of phenylketonuria patients treated early was not different from that of a homogenous population group under the same conditions. After extending the test program in 1966, 1 maple syrup urine disease, 3 homocystinurias, 3 galactosemias and 1 galactokinase deficiency were found in addition to PKU.", "contents": "[Results of a nine-year phenylketonuria (PKU) screening (author's transl)]. The percentage of children in Nordrhein-Westfalen who were tested for PKU free of charge and on a voluntary basis rose from 25.3% (1966) to 99.5% (1973). Among 1,431,999 newly born children, 262 children with suspected PKU were found, 225 of them diagnosed early and 37 late, 181 with \"typical\" and 81 with \"atypical\" PKU. Most of 102 children with late diagnosed PKU had an I.Q. of 80-50 or less, while in 95 children treated early, it was over 91 in 80% and below 90 in only 20%. There was a statistically highly significant difference in the I.Q. distribution between patients diagnosed early and those diagnosed late, while the mental development of phenylketonuria patients treated early was not different from that of a homogenous population group under the same conditions. After extending the test program in 1966, 1 maple syrup urine disease, 3 homocystinurias, 3 galactosemias and 1 galactokinase deficiency were found in addition to PKU."} {"id": "PMID:164620", "title": "Adaptive character of liver glucokinase.", "content": "1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.", "contents": "Adaptive character of liver glucokinase. 1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose."} {"id": "PMID:164622", "title": "[Diagnosis and surgical treatment of bronchial carcinoma - a report on 1000 cases (author's transl)].", "content": "One thousand cases of bronchial carcinoma, which had been treated in the Chirurgische Universit\u00e4tsklinik Erlangen in 17 years, are reported. 63,2% were either primarily inoperable or found to be so after an exploratory laparotomy; Only 32,4% of all patients were admitted in the first 3 months, 17,6% after more than 12 months, Squamous epithelial carcinoma was the most frequent histological type (51,2%), then came small cell carcinoma (16,4%), dedifferentiated carcinoma (5,1%) and adenocarcinoma (4,1%). The best results of operative treatment were obtained with lobectomy in Stage I with a five year survival rate of 45%. In Stage II, pneumonectomy is the satisfactory operation (no five year cure with lobectomy, but 25,2% with pneumonectomy). Exploratory thoracotomy does not shorten the life expectancy and it should therefore be performed in doubtful cases.", "contents": "[Diagnosis and surgical treatment of bronchial carcinoma - a report on 1000 cases (author's transl)]. One thousand cases of bronchial carcinoma, which had been treated in the Chirurgische Universit\u00e4tsklinik Erlangen in 17 years, are reported. 63,2% were either primarily inoperable or found to be so after an exploratory laparotomy; Only 32,4% of all patients were admitted in the first 3 months, 17,6% after more than 12 months, Squamous epithelial carcinoma was the most frequent histological type (51,2%), then came small cell carcinoma (16,4%), dedifferentiated carcinoma (5,1%) and adenocarcinoma (4,1%). The best results of operative treatment were obtained with lobectomy in Stage I with a five year survival rate of 45%. In Stage II, pneumonectomy is the satisfactory operation (no five year cure with lobectomy, but 25,2% with pneumonectomy). Exploratory thoracotomy does not shorten the life expectancy and it should therefore be performed in doubtful cases."} {"id": "PMID:164623", "title": "[The importance of estrogen receptors in the pharmacotherapy of mammary carcinoma (author's transl)].", "content": "The physiological effect of estrogens on the estrogen-dependent target organs is mediated by estrogen receptors which are present in the cytoplasm of estrogen-sensitive cells. By determining the estrogen receptors in mammary carcinoma tissue, information may be obtained on the susceptibility of the tumor concerned to hormones. As a novel pharmacological principle, the anti-estrogens are able to blockade the hormonal effect of endogenous estrogens on the tissue of the mammary carcinoma. Possible relationships between prolactin and mammary carcinoma become apparent. From the pharmacologist's point of view, these questions are of particular importance in relation to the possibility of predisposition to mammary carcinoma through treatment with reserpine, which is at present under discussion.", "contents": "[The importance of estrogen receptors in the pharmacotherapy of mammary carcinoma (author's transl)]. The physiological effect of estrogens on the estrogen-dependent target organs is mediated by estrogen receptors which are present in the cytoplasm of estrogen-sensitive cells. By determining the estrogen receptors in mammary carcinoma tissue, information may be obtained on the susceptibility of the tumor concerned to hormones. As a novel pharmacological principle, the anti-estrogens are able to blockade the hormonal effect of endogenous estrogens on the tissue of the mammary carcinoma. Possible relationships between prolactin and mammary carcinoma become apparent. From the pharmacologist's point of view, these questions are of particular importance in relation to the possibility of predisposition to mammary carcinoma through treatment with reserpine, which is at present under discussion."} {"id": "PMID:164624", "title": "Comparative analysis of deletion and base-change mutabilities of Escherichia coli B strains differing in DNA repair capacity (wild-type, uvrA-, polA-, recA-) by various mutagens.", "content": "Dose-response curves were compared for deletions [ColBR (resistant to colicin B) mutations being more than 80% deletions] and base changes (reversion of argFam to prototrophy argplus) induced in the same set of E. coli strains (wild-type for DNA repair, uvrA-, polA- and recA-) by N-methyl-N'-nitro-N-nitrosoguanidine (NTG), ethyl methanesulfonate (EMS), hydroxylamine (HA), 4-nitroquinoline I-oxide (4NQO), mitomycin C (MTC, UV and X-rays. All these agents induced deletions as well as base changes in the wild-type strain. Thus chemical mutagenesis differed in E. coli and bacteriophages in vitro, for HA, NTG, EMS and perhaps UV produced only point mutations in phage Tr. The patterns of deletion and base-change mutability in E. coli were surprisingly similar. (I) The recombination less recA- strain was mutable by only three (NTG, EMS, HA) of the seven mutagens for either deletions or base changes. (2) The uvrA- strain, unable to excise pyrimidine dimers, was very highly mutable by 4NQO and UV but immutable by MTC for both deletions and base changes. (3) The polA- strain, defective in DNA polymerase I due to a non-suppressible mutation, was very highly mutable by HA and highly mutable by MTC and 4NQO for both deletions and base changes but was highly mutable only for deletions by UV and X-rays, remaining normally mutable by the other agents for both deletions and base changes despite its high sensitivity to their inactivating action. We conclude that errors in the recA-dependent repair of induced DNA damage (after 4NQO, MTC, UV and X-rays) or errors in replication enhanced by damage to the replication system or to the template strands (after NTG, EMS, and HA) give rise to deletions as well as to base changes. From a comparative analysis of 14 dose-response curves for deletions and base changes, we conclude that the order of mutagenic efficiency relative to killing is (EMS, NTG) greater than (UV, 4NQO) greater than HA greater than (X-rays, MTC), and that X-rays, 4NQO, HA and MTC induce more ColBR deletions than Argplus base changes, whereas UV and EMS induce ColBR deletions and Argplus base changes at nearly equal rates and the specificity of NTG is intermediate between these two types.", "contents": "Comparative analysis of deletion and base-change mutabilities of Escherichia coli B strains differing in DNA repair capacity (wild-type, uvrA-, polA-, recA-) by various mutagens. Dose-response curves were compared for deletions [ColBR (resistant to colicin B) mutations being more than 80% deletions] and base changes (reversion of argFam to prototrophy argplus) induced in the same set of E. coli strains (wild-type for DNA repair, uvrA-, polA- and recA-) by N-methyl-N'-nitro-N-nitrosoguanidine (NTG), ethyl methanesulfonate (EMS), hydroxylamine (HA), 4-nitroquinoline I-oxide (4NQO), mitomycin C (MTC, UV and X-rays. All these agents induced deletions as well as base changes in the wild-type strain. Thus chemical mutagenesis differed in E. coli and bacteriophages in vitro, for HA, NTG, EMS and perhaps UV produced only point mutations in phage Tr. The patterns of deletion and base-change mutability in E. coli were surprisingly similar. (I) The recombination less recA- strain was mutable by only three (NTG, EMS, HA) of the seven mutagens for either deletions or base changes. (2) The uvrA- strain, unable to excise pyrimidine dimers, was very highly mutable by 4NQO and UV but immutable by MTC for both deletions and base changes. (3) The polA- strain, defective in DNA polymerase I due to a non-suppressible mutation, was very highly mutable by HA and highly mutable by MTC and 4NQO for both deletions and base changes but was highly mutable only for deletions by UV and X-rays, remaining normally mutable by the other agents for both deletions and base changes despite its high sensitivity to their inactivating action. We conclude that errors in the recA-dependent repair of induced DNA damage (after 4NQO, MTC, UV and X-rays) or errors in replication enhanced by damage to the replication system or to the template strands (after NTG, EMS, and HA) give rise to deletions as well as to base changes. From a comparative analysis of 14 dose-response curves for deletions and base changes, we conclude that the order of mutagenic efficiency relative to killing is (EMS, NTG) greater than (UV, 4NQO) greater than HA greater than (X-rays, MTC), and that X-rays, 4NQO, HA and MTC induce more ColBR deletions than Argplus base changes, whereas UV and EMS induce ColBR deletions and Argplus base changes at nearly equal rates and the specificity of NTG is intermediate between these two types."} {"id": "PMID:164627", "title": "Viral hepatitis, type A. Identification by specific complement fixation and immune adherence tests.", "content": "Hepatitis A antibody was detected by specific immune adherence and complement-fixation tests in a study involving 473 serum specimens from 20 patients who had viral hepatitis, Type A. In all 20 patients who had no detectable immune adherence antibody (less than 1:5) before onset of hepatitis high levels (greater than or equal to 1:1024) developed one to four weeks later, occasionally reaching peak levels exceeding greater than or equal to 1:81,920 several months thereafter. Five to 10 years later the immune adherence antibody levels ranged between 1:640 and 1:20,480. In general, the complement-fixation test was not as sensitive or as specific as the immune adherence test. These findings indicate that the immune adherence test should be a valuable tool for diagnosis, for epidemiologic surveys, for identification of susceptible and immune persons, for quantitative assays of gamma globulin and for identification of hepatitis A virus in attempts to propagate the virus in cell culture.", "contents": "Viral hepatitis, type A. Identification by specific complement fixation and immune adherence tests. Hepatitis A antibody was detected by specific immune adherence and complement-fixation tests in a study involving 473 serum specimens from 20 patients who had viral hepatitis, Type A. In all 20 patients who had no detectable immune adherence antibody (less than 1:5) before onset of hepatitis high levels (greater than or equal to 1:1024) developed one to four weeks later, occasionally reaching peak levels exceeding greater than or equal to 1:81,920 several months thereafter. Five to 10 years later the immune adherence antibody levels ranged between 1:640 and 1:20,480. In general, the complement-fixation test was not as sensitive or as specific as the immune adherence test. These findings indicate that the immune adherence test should be a valuable tool for diagnosis, for epidemiologic surveys, for identification of susceptible and immune persons, for quantitative assays of gamma globulin and for identification of hepatitis A virus in attempts to propagate the virus in cell culture."} {"id": "PMID:164628", "title": "Plasma lipids and lipoproteins in vegetarians and controls.", "content": "The possible effect of diet on plasma lipids was investigated in a group of vegetarians. Seventy-three men and 43 women who had adhered to a vegetarian diet for an average of three years were studied in the fasting state and compared with a randomly selected group of controls matched for age and sex. Mean cholesterol levels in milligrams per deciliter for vegetarians and controls, respectively, were 126 and 184; low-density lipoprotein, 73 and 118; very-low-density lipoprotein, 11.8 and 17.2; high-density lipoproteins, 42 and 49; and mean triglyceride levels 59 and 86. Mean weight and subscapular skinfold thicknesses were 58 kg and 6 mm for vegetarians and 73 kg and 17 mm for controls. Similar differences in lipid levels were found between subgroups of 42 vegetarians and controls with identical mean weights. Multiple regression analyses showed that consumption of dairy foods and eggs, but not body weight, was associated with the lipoprotein and cholesterol findings.", "contents": "Plasma lipids and lipoproteins in vegetarians and controls. The possible effect of diet on plasma lipids was investigated in a group of vegetarians. Seventy-three men and 43 women who had adhered to a vegetarian diet for an average of three years were studied in the fasting state and compared with a randomly selected group of controls matched for age and sex. Mean cholesterol levels in milligrams per deciliter for vegetarians and controls, respectively, were 126 and 184; low-density lipoprotein, 73 and 118; very-low-density lipoprotein, 11.8 and 17.2; high-density lipoproteins, 42 and 49; and mean triglyceride levels 59 and 86. Mean weight and subscapular skinfold thicknesses were 58 kg and 6 mm for vegetarians and 73 kg and 17 mm for controls. Similar differences in lipid levels were found between subgroups of 42 vegetarians and controls with identical mean weights. Multiple regression analyses showed that consumption of dairy foods and eggs, but not body weight, was associated with the lipoprotein and cholesterol findings."} {"id": "PMID:164634", "title": "Reovirus antibody patterns in dogs: a trial for the application of principal component analysis to seroepidemiology.", "content": "In 100 dogs in Morioka and its vicinity serologically surveyed for reovirus infection, there were significant correlations between hemagglutination-inhibiting and neutralizing antibody titers of the same virus types. In order to establish a proper index for the evaluation of infection, principal component analysis was applied to the analysis of data, including standard immune sera. Of nine samples of matrix examined, correlation matrix of 6 variables was suggested to afford the most proper result. Essential information from the original data was accounted for by factor loadings of the first 3 components. The 6 attributes of serum antibody were classified into three groups. In a scatter diagram serum samples were classified also into three major groups corresponding to the three reovirus types, and the serotypic pattern of infection was clearly visualized.", "contents": "Reovirus antibody patterns in dogs: a trial for the application of principal component analysis to seroepidemiology. In 100 dogs in Morioka and its vicinity serologically surveyed for reovirus infection, there were significant correlations between hemagglutination-inhibiting and neutralizing antibody titers of the same virus types. In order to establish a proper index for the evaluation of infection, principal component analysis was applied to the analysis of data, including standard immune sera. Of nine samples of matrix examined, correlation matrix of 6 variables was suggested to afford the most proper result. Essential information from the original data was accounted for by factor loadings of the first 3 components. The 6 attributes of serum antibody were classified into three groups. In a scatter diagram serum samples were classified also into three major groups corresponding to the three reovirus types, and the serotypic pattern of infection was clearly visualized."} {"id": "PMID:164636", "title": "Further studies on ACTH secretion from pituitary grafts in the hypophysiotrophic area.", "content": "Resting and stress-induced plasma corticosterone concentrations in adult male hypophysectomized rats bearing a pituitary homograft in the hypothalamus were determined fluorimetrically. Plasma corticosterone resting levels were maintained and a significant elevation of these levels in response to stress occurred only in those rats in which the graft was in the medial basal hypothalamus (hypophysiotrophic area, HTA) and the implant was connected with the median eminence. If these latter connections of the graft in the HTA did not exist, resting plasma corticosterone concentrations were reduced and the applied stress did not induce any elevation of the low pre-stress levels. On the basis of the present and previous findings, it is assumed that the site of CRF production is the median eminence region.", "contents": "Further studies on ACTH secretion from pituitary grafts in the hypophysiotrophic area. Resting and stress-induced plasma corticosterone concentrations in adult male hypophysectomized rats bearing a pituitary homograft in the hypothalamus were determined fluorimetrically. Plasma corticosterone resting levels were maintained and a significant elevation of these levels in response to stress occurred only in those rats in which the graft was in the medial basal hypothalamus (hypophysiotrophic area, HTA) and the implant was connected with the median eminence. If these latter connections of the graft in the HTA did not exist, resting plasma corticosterone concentrations were reduced and the applied stress did not induce any elevation of the low pre-stress levels. On the basis of the present and previous findings, it is assumed that the site of CRF production is the median eminence region."} {"id": "PMID:164637", "title": "Adrenal cortical secretion in response to pilocarpine in dogs with hypothalamic lesions.", "content": "Adrenal venous blood samples were collected from conscious and anesthetized dogs before and after an injection of pilocarpine and were analyzed for 17-hydroxycorticosteriods (17-OHCS). In conscious dogs the adrenal 17-OHCS secretion rate increased from a pre-injection secretion rate of 0.11 plus or minus 0.014 to 1.58 plus or minus 0.069 (mean plus or minus SE) mug/kg/min following an intravenous injection of pilocarpine (0.3 mg/kg); there was a return to the baseline level by 120 min. In anesthetized dogs a marked increase in adrenal 17-OHCS secretion was also observed, which was completely abolished by hypophysectomy A noticeable impairment of the adrenocortical response to pilocarpine was found to be produced by radio-frequency-current lesions of the anterior median eminence. A partial depression of the response was also observed in dogs with the anterior ventromedial hypothalamic lesions. Lesions destroying other hypothalamic areas were found to be without significant effect upon the adrenal cortical secretory response to pilocarpine.", "contents": "Adrenal cortical secretion in response to pilocarpine in dogs with hypothalamic lesions. Adrenal venous blood samples were collected from conscious and anesthetized dogs before and after an injection of pilocarpine and were analyzed for 17-hydroxycorticosteriods (17-OHCS). In conscious dogs the adrenal 17-OHCS secretion rate increased from a pre-injection secretion rate of 0.11 plus or minus 0.014 to 1.58 plus or minus 0.069 (mean plus or minus SE) mug/kg/min following an intravenous injection of pilocarpine (0.3 mg/kg); there was a return to the baseline level by 120 min. In anesthetized dogs a marked increase in adrenal 17-OHCS secretion was also observed, which was completely abolished by hypophysectomy A noticeable impairment of the adrenocortical response to pilocarpine was found to be produced by radio-frequency-current lesions of the anterior median eminence. A partial depression of the response was also observed in dogs with the anterior ventromedial hypothalamic lesions. Lesions destroying other hypothalamic areas were found to be without significant effect upon the adrenal cortical secretory response to pilocarpine."} {"id": "PMID:164641", "title": "Luteomas of pregnancy.", "content": "Since its original description in 1963, the pregnancy luteoma has been a controversial entity both clinically and pathologically. The most important questions which have been asked are: Is the luteoma a true neoplasm or does it represent simply an abnormal response to the hormones of pregnancy? What is the relation between the tumor and certain endocrinopathies that are associated with these lesions? This study of 20 cases collected from the files of the Emil Novak Ovarian Tumor Registry and the Pathology Section of the Baltimore City Hospitals directs its attention to these critical clinicopathologic features.", "contents": "Luteomas of pregnancy. Since its original description in 1963, the pregnancy luteoma has been a controversial entity both clinically and pathologically. The most important questions which have been asked are: Is the luteoma a true neoplasm or does it represent simply an abnormal response to the hormones of pregnancy? What is the relation between the tumor and certain endocrinopathies that are associated with these lesions? This study of 20 cases collected from the files of the Emil Novak Ovarian Tumor Registry and the Pathology Section of the Baltimore City Hospitals directs its attention to these critical clinicopathologic features."} {"id": "PMID:164642", "title": "Prophylactic antibiotics in cesarean section.", "content": "Using a random selection procedure, 100 patients were evaluated in order to determine the value of prophylactic antibiotics in cesarean section. All patients were evaluated for febrile morbidity, and specific infection sites were recorded. Significant differences were found between the treated and control groups and between cesarean sections performed prior to the onset of labor and after the onset of labor.", "contents": "Prophylactic antibiotics in cesarean section. Using a random selection procedure, 100 patients were evaluated in order to determine the value of prophylactic antibiotics in cesarean section. All patients were evaluated for febrile morbidity, and specific infection sites were recorded. Significant differences were found between the treated and control groups and between cesarean sections performed prior to the onset of labor and after the onset of labor."} {"id": "PMID:164643", "title": "Virilization associated with bilateral luteomas of pregnancy.", "content": "A case of maternal virilization associated with bilateral luteomas of pregnancy is described. Urinary 17-ketosteroids and plasma testosterone fell from markedly abnormal values to normal limits within 2 weeks of delivery. However, symptoms of virilization persisted in the postpartum state. A possible relation between polycystic ovarian syndrome in the nonpregnant state and luteoma of pregnancy is proposed.", "contents": "Virilization associated with bilateral luteomas of pregnancy. A case of maternal virilization associated with bilateral luteomas of pregnancy is described. Urinary 17-ketosteroids and plasma testosterone fell from markedly abnormal values to normal limits within 2 weeks of delivery. However, symptoms of virilization persisted in the postpartum state. A possible relation between polycystic ovarian syndrome in the nonpregnant state and luteoma of pregnancy is proposed."} {"id": "PMID:164644", "title": "A rapid solid-phase radioimmunoassay specific for human chorionic gonadotropin in gestational trophoblastic disease.", "content": "A rapid solid-phase radioimmunoassay (RIA) specific for human chorionic gonadotropin (hCG) has been used for the measurement of serum hCG activity in patients with molar pregnancy and gestational trophoblastic disease (GTD). Serum hCG regression as determined by the specific RIA method after evacuation of uncomplicated molar pregnancy was noted to occur over a longer duration of time than previously reported from this Center using a nonspecific RIA system which measures human luteinizing hormone (hLH) and hCG simultaneously. Therapy for proliferative trophoblastic disease was withheld after evacuation of molar pregnancy while the serum hCG level regressed normally, but was instituted when the serum hCG level rose or plateaued for more than two consecutive weeks. Serum hCG levels in patients requiring chemotherapy for GTD were also more accurately monitored with the specific RIA method than with the nonspecific technic. Therapy was based solely on the hCG titer rather than the subsidence of toxicity, as has been our practice in the past. As a result, the duration of hospitalization, total dose of drug required for remission, and toxic side effects were substantially reduced without sacrificing the effectiveness of chemotherapy.", "contents": "A rapid solid-phase radioimmunoassay specific for human chorionic gonadotropin in gestational trophoblastic disease. A rapid solid-phase radioimmunoassay (RIA) specific for human chorionic gonadotropin (hCG) has been used for the measurement of serum hCG activity in patients with molar pregnancy and gestational trophoblastic disease (GTD). Serum hCG regression as determined by the specific RIA method after evacuation of uncomplicated molar pregnancy was noted to occur over a longer duration of time than previously reported from this Center using a nonspecific RIA system which measures human luteinizing hormone (hLH) and hCG simultaneously. Therapy for proliferative trophoblastic disease was withheld after evacuation of molar pregnancy while the serum hCG level regressed normally, but was instituted when the serum hCG level rose or plateaued for more than two consecutive weeks. Serum hCG levels in patients requiring chemotherapy for GTD were also more accurately monitored with the specific RIA method than with the nonspecific technic. Therapy was based solely on the hCG titer rather than the subsidence of toxicity, as has been our practice in the past. As a result, the duration of hospitalization, total dose of drug required for remission, and toxic side effects were substantially reduced without sacrificing the effectiveness of chemotherapy."} {"id": "PMID:164648", "title": "Thymidine kinase activity in cerebrospinal fluid of rabbits with Herpesvirus hominis encephalitis.", "content": "The rabbit model of Herpesvirus hominis (HVH) encephalitis was utilized to determine whether thymidine (TdR) kinase (EC. 2.7.1.2.1), AN EARLY ENZYME IN THe HVH replicative cycle, is present in the cerebrospinal fluid (CSF) of rabbits with HVH encephalitis. The mean TdR kinase activity in CSF from infected rabbits was 2.30 plus or minus 1.69 pmol product/120 min/100 mul CSF, while the mean TdR kinase activity of uninfected CSF was 0.34 plus or minus 0.25. The enzyme appeared to be cell associated since the TdR kinase activity in the sedimented cell suspension was 5.08 plus or minus 2.93 (seven values) while the supernatant activity was 0.14 plus or minus 0.31 (seven values). To allow a comparison of TdR kinase from infected rabbit CSF with HVH and rabbit mononuclear cell TdR kinase, the mean ratio of TdR kinase activity at pH 6.0/pH 8.0, for infected rabbit CSF is intermediate between the ratio for HVH TdR kinase (P less than 0.001) and rabbit mononuclear cell TdR kinase (P less than 0.05).", "contents": "Thymidine kinase activity in cerebrospinal fluid of rabbits with Herpesvirus hominis encephalitis. The rabbit model of Herpesvirus hominis (HVH) encephalitis was utilized to determine whether thymidine (TdR) kinase (EC. 2.7.1.2.1), AN EARLY ENZYME IN THe HVH replicative cycle, is present in the cerebrospinal fluid (CSF) of rabbits with HVH encephalitis. The mean TdR kinase activity in CSF from infected rabbits was 2.30 plus or minus 1.69 pmol product/120 min/100 mul CSF, while the mean TdR kinase activity of uninfected CSF was 0.34 plus or minus 0.25. The enzyme appeared to be cell associated since the TdR kinase activity in the sedimented cell suspension was 5.08 plus or minus 2.93 (seven values) while the supernatant activity was 0.14 plus or minus 0.31 (seven values). To allow a comparison of TdR kinase from infected rabbit CSF with HVH and rabbit mononuclear cell TdR kinase, the mean ratio of TdR kinase activity at pH 6.0/pH 8.0, for infected rabbit CSF is intermediate between the ratio for HVH TdR kinase (P less than 0.001) and rabbit mononuclear cell TdR kinase (P less than 0.05)."} {"id": "PMID:164653", "title": "Cyclic nucleotide metabolism coupled to cytodifferentiation of Blastocladiella emersonii.", "content": "Cyclic GMP and cyclic AMP levels during growth and differentiation of B. emersonii were measured by use of chemical, biochemical, and immunologic assays. Of particular interest was the finding that net synthesis of cyclic GMP occurred during a single stage of its life cycle, sporulation, when intracellular levels increased 50- to 100-fold in a process requiring protein and RNA synthesis.", "contents": "Cyclic nucleotide metabolism coupled to cytodifferentiation of Blastocladiella emersonii. Cyclic GMP and cyclic AMP levels during growth and differentiation of B. emersonii were measured by use of chemical, biochemical, and immunologic assays. Of particular interest was the finding that net synthesis of cyclic GMP occurred during a single stage of its life cycle, sporulation, when intracellular levels increased 50- to 100-fold in a process requiring protein and RNA synthesis."} {"id": "PMID:164654", "title": "Mutant hamster cells exhibiting a pleiotropic effect on carbohydrate metabolism.", "content": "Sixty-seven galactose negative (Gal minus) clones were established from survivors after treatment of Chinese hamster lung (V79) cells with 5-bromodeoxyuridine and black light. The mutational origin of these clonal isolates was inferred on the basis of the previously demonstrated mutagenic action of the combined treatment, persistence of the Gal minus phenotype in cell progeny in the absence of selection, conditional lethality of three isolates, interallelic complementation, and assignment of a homologous human gene to chromosome A2. In contrast to the parental cells, Gal minus mutants could not utilize exogenous galactose, mannose, fructose, galactose 1-phosphate, glucose 1-phosphate, or glucose 6-phosphate. Permeation of galactose into mutant cells appeared unimpaired. In intra- and interspecific cell hybrids, the mutation causing the Gal minus phenotype behaved like a recessive character. The pleiotropic nutritional response was due not to deficiency of any one specific enzyme in the Leloir pathway but to significant reduction in activities of phosphoglucomutase, NADP-dependent isocitrate dehydrogenase, and perhaps other enzymes. In temperature-sensitive Gal minus mutants grown at permissive temperature or in complementing intra- and interspecific cell hybrids, the activities of these enzymes were restored to normal levels, accompanied by a regained ability to use the particular hexoses or hexose monophosphates. We postulate that the change from Gal + to Gal minus phenotype in hamster cells could be due to mutations at a regulatory gene locus, or at a yet unknown locus with enzymic defect that causes secondary metabolic imbalances.", "contents": "Mutant hamster cells exhibiting a pleiotropic effect on carbohydrate metabolism. Sixty-seven galactose negative (Gal minus) clones were established from survivors after treatment of Chinese hamster lung (V79) cells with 5-bromodeoxyuridine and black light. The mutational origin of these clonal isolates was inferred on the basis of the previously demonstrated mutagenic action of the combined treatment, persistence of the Gal minus phenotype in cell progeny in the absence of selection, conditional lethality of three isolates, interallelic complementation, and assignment of a homologous human gene to chromosome A2. In contrast to the parental cells, Gal minus mutants could not utilize exogenous galactose, mannose, fructose, galactose 1-phosphate, glucose 1-phosphate, or glucose 6-phosphate. Permeation of galactose into mutant cells appeared unimpaired. In intra- and interspecific cell hybrids, the mutation causing the Gal minus phenotype behaved like a recessive character. The pleiotropic nutritional response was due not to deficiency of any one specific enzyme in the Leloir pathway but to significant reduction in activities of phosphoglucomutase, NADP-dependent isocitrate dehydrogenase, and perhaps other enzymes. In temperature-sensitive Gal minus mutants grown at permissive temperature or in complementing intra- and interspecific cell hybrids, the activities of these enzymes were restored to normal levels, accompanied by a regained ability to use the particular hexoses or hexose monophosphates. We postulate that the change from Gal + to Gal minus phenotype in hamster cells could be due to mutations at a regulatory gene locus, or at a yet unknown locus with enzymic defect that causes secondary metabolic imbalances."} {"id": "PMID:164655", "title": "Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man.", "content": "Insulin receptors have been demonstrated on mononuclear leukocytes prepared by centrifugation of buffy coats from normal blood donors on Ficoll-Hypaque gradients. The cell type that specifically binds insulin in this mixture of lymphocytes and monocytes has never been clearly identified, although it was assumed to be the lymphocyte since this cell constitutes about 80% of the population. In the present studies, insulin-binding assays were performed on the mononuclear leukocyte preparation before and after selective depletion or enrichment for monocytes using glass wool or Sephadex G-10 adherence columns. The amount of 125-I-labeled insulin specifically bound correlated significantly with the number of monocytes but not with the number of B or T lymphocytes. Approximately 90% of the specific insulin binding of this preparation could be accounted for by its content of monocytes. The amount of binding was unaffected by phagocytosis of latex particles or by metabolic inhibitors added to prevent endocytosis. Autoradiograms made on smears of whole peripheral blood and mononuclear leukocytes demonstrated that all of the cells that bound 125-I-labeled insulin were large mononulcear cells, 85-90% of which could be identified as monocytes by morphological criteria or by the functional criterion of latex particle ingestion. Since insulin receptor concentration may be altered in disease states in man, it is essential, when using this cell population for detecting such changes, to quantitate the number of monocytes in the preparation so that the insulin-binding data can be appropriately interpreted.", "contents": "Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man. Insulin receptors have been demonstrated on mononuclear leukocytes prepared by centrifugation of buffy coats from normal blood donors on Ficoll-Hypaque gradients. The cell type that specifically binds insulin in this mixture of lymphocytes and monocytes has never been clearly identified, although it was assumed to be the lymphocyte since this cell constitutes about 80% of the population. In the present studies, insulin-binding assays were performed on the mononuclear leukocyte preparation before and after selective depletion or enrichment for monocytes using glass wool or Sephadex G-10 adherence columns. The amount of 125-I-labeled insulin specifically bound correlated significantly with the number of monocytes but not with the number of B or T lymphocytes. Approximately 90% of the specific insulin binding of this preparation could be accounted for by its content of monocytes. The amount of binding was unaffected by phagocytosis of latex particles or by metabolic inhibitors added to prevent endocytosis. Autoradiograms made on smears of whole peripheral blood and mononuclear leukocytes demonstrated that all of the cells that bound 125-I-labeled insulin were large mononulcear cells, 85-90% of which could be identified as monocytes by morphological criteria or by the functional criterion of latex particle ingestion. Since insulin receptor concentration may be altered in disease states in man, it is essential, when using this cell population for detecting such changes, to quantitate the number of monocytes in the preparation so that the insulin-binding data can be appropriately interpreted."} {"id": "PMID:164656", "title": "Colchicine affects kinetics of concanavalin a-mediated agglutination of hepatoma cells and plasma membranes from liver and hepatoma cells.", "content": "Concanavalin A-mediated agglutination reactions of hepatoma cells [AH-130F(N)] and isolated liver cells, as well as of plasma membranes prepared from the liver and hepatoma, were investigated kinetically together with the effect of colchicine upon them. Concanavalin A-mediated agglutination of hepatoma cells at 25 degrees proceeded with biphasic kinetics (first and second stages of agglutination), while no appreciable agglutination of liver cells was observed in the presence of concanavalin A. The plasma membranes from the liver and hepatoma cells were similarly agglutinated with concanavalin A at 25 degrees but not at 0 degrees. The concanavalin A-mediated membrane agglutination proceeded with monophasic kinetics and was incomplete. Colchicine inhibited preferentially the second stage of concanavalin A-mediated agglutination of hepatoma cells, but it did not affect the concanavalin A-mediated agglutination of plasma membranes of both types of cells.", "contents": "Colchicine affects kinetics of concanavalin a-mediated agglutination of hepatoma cells and plasma membranes from liver and hepatoma cells. Concanavalin A-mediated agglutination reactions of hepatoma cells [AH-130F(N)] and isolated liver cells, as well as of plasma membranes prepared from the liver and hepatoma, were investigated kinetically together with the effect of colchicine upon them. Concanavalin A-mediated agglutination of hepatoma cells at 25 degrees proceeded with biphasic kinetics (first and second stages of agglutination), while no appreciable agglutination of liver cells was observed in the presence of concanavalin A. The plasma membranes from the liver and hepatoma cells were similarly agglutinated with concanavalin A at 25 degrees but not at 0 degrees. The concanavalin A-mediated membrane agglutination proceeded with monophasic kinetics and was incomplete. Colchicine inhibited preferentially the second stage of concanavalin A-mediated agglutination of hepatoma cells, but it did not affect the concanavalin A-mediated agglutination of plasma membranes of both types of cells."} {"id": "PMID:164657", "title": "Regulation of development in Myxococcus xanthus: effect of 3':5'-cyclic AMP, ADP, and nutrition.", "content": "An assay was developed to study the regulation of fruiting in Myxococcus xanthus. The nucleotides, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and adenosine diphosphate (ADP), were found to greatly stimulate fruiting under the assay conditions. Very sharp concentration optima were observed. Even under conditions of starvation, these nucleotides greatly increased the number of aggregation sites. Nutrition was found to influence fruiting body morphology. The effect of amino acids on the nucleotide stimulation of fruiting was studied under our assay conditions. L-Methionine and L-isoleucine (1 mM) completely blocked either L-threonine or D,L-diaminopimelic acid synergistically enhanced the amount of fruiting in the presence of these nucleotides. The data presented suggest the existence of differentiation-related regulatory compounds in M. xanthus.", "contents": "Regulation of development in Myxococcus xanthus: effect of 3':5'-cyclic AMP, ADP, and nutrition. An assay was developed to study the regulation of fruiting in Myxococcus xanthus. The nucleotides, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and adenosine diphosphate (ADP), were found to greatly stimulate fruiting under the assay conditions. Very sharp concentration optima were observed. Even under conditions of starvation, these nucleotides greatly increased the number of aggregation sites. Nutrition was found to influence fruiting body morphology. The effect of amino acids on the nucleotide stimulation of fruiting was studied under our assay conditions. L-Methionine and L-isoleucine (1 mM) completely blocked either L-threonine or D,L-diaminopimelic acid synergistically enhanced the amount of fruiting in the presence of these nucleotides. The data presented suggest the existence of differentiation-related regulatory compounds in M. xanthus."} {"id": "PMID:164658", "title": "Contribution of the peptide backbone to the action of oxytocin analogs.", "content": "This investigation was undertaken to evaluate the functional contribution of the peptide backbone of oxytocin in its interaction with receptor. Corey-Pauling-Koltun models of (Gly-7) deaminooxytocin, deaminotocinamide, and their respective retro-D-analogs built in any specific conformation (e.g., the Walter-Urry model for oxytocin) have a quai-equivalent topochemical arrangement of amino-acid side chains; however, the CO and NH elements of the peptide backbone of the retro-D-analog are reversed. The retro-D-analogs of deaminotocinamide and (Gly-7) deaminooxytocin (prepared using D-alle for L-Ile) and their respective N-formyl derivatives were assayed for uterotonic activity relative to related L-peptides. All retro-D-analogs (tested at concentrations ranging from 10-10 to 10-5 M) were devoid of angonistic (or antagonistic) activity in the isolated rat uterus, except for the retro-D-(D-alle-3, Gly-7) deaminooxytocinamine, which retains a terminal NH-2 group on the tail; the latter is a partial agonist with very low affinity. The results obtained with retro-D-analogs indicate that one or more of the elements of the peptide backbone of the tocinamide ring are essential for \"occupation\" and \"activation\" of uterine receptors. Oxytocin action may be the resultant of multiple hydrogen-bonding interactions between CO, NH, NH-2, and OH groups of the hormone with complementary groups on receptor, made possible by appropriate hydrophobic bonding.", "contents": "Contribution of the peptide backbone to the action of oxytocin analogs. This investigation was undertaken to evaluate the functional contribution of the peptide backbone of oxytocin in its interaction with receptor. Corey-Pauling-Koltun models of (Gly-7) deaminooxytocin, deaminotocinamide, and their respective retro-D-analogs built in any specific conformation (e.g., the Walter-Urry model for oxytocin) have a quai-equivalent topochemical arrangement of amino-acid side chains; however, the CO and NH elements of the peptide backbone of the retro-D-analog are reversed. The retro-D-analogs of deaminotocinamide and (Gly-7) deaminooxytocin (prepared using D-alle for L-Ile) and their respective N-formyl derivatives were assayed for uterotonic activity relative to related L-peptides. All retro-D-analogs (tested at concentrations ranging from 10-10 to 10-5 M) were devoid of angonistic (or antagonistic) activity in the isolated rat uterus, except for the retro-D-(D-alle-3, Gly-7) deaminooxytocinamine, which retains a terminal NH-2 group on the tail; the latter is a partial agonist with very low affinity. The results obtained with retro-D-analogs indicate that one or more of the elements of the peptide backbone of the tocinamide ring are essential for \"occupation\" and \"activation\" of uterine receptors. Oxytocin action may be the resultant of multiple hydrogen-bonding interactions between CO, NH, NH-2, and OH groups of the hormone with complementary groups on receptor, made possible by appropriate hydrophobic bonding."} {"id": "PMID:164659", "title": "Distribution of membrane particles and gap junctions in normal and transformed 3T3 cells studied in situ, in suspension, and treated with concanavalin A.", "content": "Freeze-fracture techniques were used to study the ultrastructural distribution of plasma membrane particles in cultures of normal Balb/c and Swiss 3T3 and simian virus 40- or murine sarcoma virus-transformed fibroblasts. No apparent differences were observed. Cultures fixed in situ show a seemingly random distribution of membrane particles both in normal or in transformed cells. Treatment of cell cultures in situ with concanavalin A does not result in an altered pattern of particle distribution. EDTA-induced suspension of normal or transformed cells does not result, per se, in modification of the type of membrane particle distribution seen in cells fixed in situ. However, upon further incubation, a proportion of normal or transformed cells in suspension show a varying degree of particle aggregation following a network pattern. Concanavalin A treatment of normal and transformed cells in suspension does not result in a specific change of the pattern of particle distribution. Because it has been established that treatment with concanavalin A of simian virus 40-transformed Balb/c 3T3 fibroblasts causes pronounced clustering of the concanavalin A receptors at the outer-surface, our results probably imply independence of membrane particles and concanavalin A receptors of these transformed cells.", "contents": "Distribution of membrane particles and gap junctions in normal and transformed 3T3 cells studied in situ, in suspension, and treated with concanavalin A. Freeze-fracture techniques were used to study the ultrastructural distribution of plasma membrane particles in cultures of normal Balb/c and Swiss 3T3 and simian virus 40- or murine sarcoma virus-transformed fibroblasts. No apparent differences were observed. Cultures fixed in situ show a seemingly random distribution of membrane particles both in normal or in transformed cells. Treatment of cell cultures in situ with concanavalin A does not result in an altered pattern of particle distribution. EDTA-induced suspension of normal or transformed cells does not result, per se, in modification of the type of membrane particle distribution seen in cells fixed in situ. However, upon further incubation, a proportion of normal or transformed cells in suspension show a varying degree of particle aggregation following a network pattern. Concanavalin A treatment of normal and transformed cells in suspension does not result in a specific change of the pattern of particle distribution. Because it has been established that treatment with concanavalin A of simian virus 40-transformed Balb/c 3T3 fibroblasts causes pronounced clustering of the concanavalin A receptors at the outer-surface, our results probably imply independence of membrane particles and concanavalin A receptors of these transformed cells."} {"id": "PMID:164660", "title": "Simian virus 40-related antigens in three human meningiomas with defined chromosome loss.", "content": "Two out of seven meningiomas tested in early cell cultures by indirect immunofluorescence staining showed simian virus 40 (SV40)-related tumor (T) antigen. In one tumor 90% of the cells were positive. An additional SV40-related antigen (U) was found in 10% of cells of a third tumor. These findings indicate that the meningioma cells showing a positive reaction are transformed by a papova virus that has at least partly the same antigenic properties as SV40 virus. SV40-related viral capsid (V) antigen was absent in all the meningiomas tested. No virus infectious for African green monkey kidney (AGMK) cells could be isolated. The tumors positive for T and U antigens showed the chromosome aberration typical for human meningiomas, i.e., the loss of one chromosome, G-22. The T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive meningioma cells were performed: fusion of cells pretreated with 8-azaguanine with cells premissive for SV40 led to a low percentage (0.01-0.05%) of V-antigen-positive nuclei in heterokaryon cultures. On the basis of these results, the possibility of a correlation between the meningioma, a relatively common intracranial tumor in man, and an SV40-related papova virus must be considered. It remains to be shown whether this virus is a causative agent for human meningiomas.", "contents": "Simian virus 40-related antigens in three human meningiomas with defined chromosome loss. Two out of seven meningiomas tested in early cell cultures by indirect immunofluorescence staining showed simian virus 40 (SV40)-related tumor (T) antigen. In one tumor 90% of the cells were positive. An additional SV40-related antigen (U) was found in 10% of cells of a third tumor. These findings indicate that the meningioma cells showing a positive reaction are transformed by a papova virus that has at least partly the same antigenic properties as SV40 virus. SV40-related viral capsid (V) antigen was absent in all the meningiomas tested. No virus infectious for African green monkey kidney (AGMK) cells could be isolated. The tumors positive for T and U antigens showed the chromosome aberration typical for human meningiomas, i.e., the loss of one chromosome, G-22. The T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive meningioma cells were performed: fusion of cells pretreated with 8-azaguanine with cells premissive for SV40 led to a low percentage (0.01-0.05%) of V-antigen-positive nuclei in heterokaryon cultures. On the basis of these results, the possibility of a correlation between the meningioma, a relatively common intracranial tumor in man, and an SV40-related papova virus must be considered. It remains to be shown whether this virus is a causative agent for human meningiomas."} {"id": "PMID:164661", "title": "Translation of Rous sarcoma virus RNA in a cell-free system from ascites Krebs II cells.", "content": "The template activities of the 60-70S RNA complex and of the 30-40S subunit RNA species of Rous sarcoma virus were tested in a cell-free protein-synthesizing system from mouse ascites Krebs II cells. Stimulation of protein synthesis over the endogenous background was about 2-fold with 30-40S viral RNA and about 1.3-fold with 60-70S viral RNA as template. Analysis by sodium dodecyl sulfate-gel electrophoresis showed that the predominant polypeptide synthesized in vitro in response to 30-40S RNA of Rous sarcoma virus had a molecular weight of 75,000-80,000. This polypeptide could be precipitated by antiserum against the group-specific antigens of the virus, although its molecular weight is higher than that of virion group-specific antigen proteins. Analysis of tryptic digests of the protein made in vitro indicates similarity to tryptic digests from authentic virion group-specific proteins. It is concluded that part of the RNA from Rous sarcoma virus is translated in vitro into a high-molecular-weight protein, perhaps a precursor of the virion group-specific proteins.", "contents": "Translation of Rous sarcoma virus RNA in a cell-free system from ascites Krebs II cells. The template activities of the 60-70S RNA complex and of the 30-40S subunit RNA species of Rous sarcoma virus were tested in a cell-free protein-synthesizing system from mouse ascites Krebs II cells. Stimulation of protein synthesis over the endogenous background was about 2-fold with 30-40S viral RNA and about 1.3-fold with 60-70S viral RNA as template. Analysis by sodium dodecyl sulfate-gel electrophoresis showed that the predominant polypeptide synthesized in vitro in response to 30-40S RNA of Rous sarcoma virus had a molecular weight of 75,000-80,000. This polypeptide could be precipitated by antiserum against the group-specific antigens of the virus, although its molecular weight is higher than that of virion group-specific antigen proteins. Analysis of tryptic digests of the protein made in vitro indicates similarity to tryptic digests from authentic virion group-specific proteins. It is concluded that part of the RNA from Rous sarcoma virus is translated in vitro into a high-molecular-weight protein, perhaps a precursor of the virion group-specific proteins."} {"id": "PMID:164662", "title": "Viral-related information in oncornavirus-lik particles isolated from cultures of marrow cells from leukemic patients in relapse and remission.", "content": "Characterization of ribonucleic acid content of particles released from cultures of marrow cells of leukemic patients indicates the presence of RNA molecules of size and base sequence characteristic of oncornarviruses. Seventeen marrow samples obtained from leukemic patients in relapse or in a chronic phase of the disease yielded particles containing high-molecular-weight RNA with a sedimentation velocity (about 70 S) similar to that obtained for murine oncornavirus RNA. Eight of nine marrow samples from non-leukemic patients did not yield detectable high-molecular weight RNA. Among patients in firm hematological remission, three of three samples from patients with acute lymphoblastic leukemia and three of nine samples from patients with acute myeloblastic leukemia were positive for high-molecular-weight RNA. The base sequence of the RNA in particles was characterized by synthesizing complementary (3-H)DNA in an endogenous reaction and hybridizing to excess RNA from known oncornaviruses. Hybridization of 40-60% of input complementary DNA to simian sarcoma virus RNA was detected. No monology was detected with an avian oncornavirus (Rous sarcoma virus) while an intermediate level of homology (10-30%) was detected in hybridization to murine sarcoma virus (Kirsten) and murine leukemia viruses (Rauscher, Moloney, and Gross).", "contents": "Viral-related information in oncornavirus-lik particles isolated from cultures of marrow cells from leukemic patients in relapse and remission. Characterization of ribonucleic acid content of particles released from cultures of marrow cells of leukemic patients indicates the presence of RNA molecules of size and base sequence characteristic of oncornarviruses. Seventeen marrow samples obtained from leukemic patients in relapse or in a chronic phase of the disease yielded particles containing high-molecular-weight RNA with a sedimentation velocity (about 70 S) similar to that obtained for murine oncornavirus RNA. Eight of nine marrow samples from non-leukemic patients did not yield detectable high-molecular weight RNA. Among patients in firm hematological remission, three of three samples from patients with acute lymphoblastic leukemia and three of nine samples from patients with acute myeloblastic leukemia were positive for high-molecular-weight RNA. The base sequence of the RNA in particles was characterized by synthesizing complementary (3-H)DNA in an endogenous reaction and hybridizing to excess RNA from known oncornaviruses. Hybridization of 40-60% of input complementary DNA to simian sarcoma virus RNA was detected. No monology was detected with an avian oncornavirus (Rous sarcoma virus) while an intermediate level of homology (10-30%) was detected in hybridization to murine sarcoma virus (Kirsten) and murine leukemia viruses (Rauscher, Moloney, and Gross)."} {"id": "PMID:164663", "title": "Fatty acid chain flexibility in the membranes of normal and transformed fibroblasts.", "content": "Fatty acid spin labels were used to measure the inherent flexibility of the lipid acyl chains in intact cell membranes of 3T3 mouse fibroblasts and several varieties of transformed 3T3 cells. No significant differences in inherent lipid flexibility were detected in the normal and transformed mouse fibroblasts. These results are compared with similar results obtained earlier for chick embryo fibroblasts. For the cells studied, a difference in the mobility of membrane glycoproteins of normal and transformed fibroblasts has either been demonstrated directly or inferred from differential agglutinability by other investigations. Therefore, a basis for correlating glycoprotein mobility and lipid motion in these cells was not found.", "contents": "Fatty acid chain flexibility in the membranes of normal and transformed fibroblasts. Fatty acid spin labels were used to measure the inherent flexibility of the lipid acyl chains in intact cell membranes of 3T3 mouse fibroblasts and several varieties of transformed 3T3 cells. No significant differences in inherent lipid flexibility were detected in the normal and transformed mouse fibroblasts. These results are compared with similar results obtained earlier for chick embryo fibroblasts. For the cells studied, a difference in the mobility of membrane glycoproteins of normal and transformed fibroblasts has either been demonstrated directly or inferred from differential agglutinability by other investigations. Therefore, a basis for correlating glycoprotein mobility and lipid motion in these cells was not found."} {"id": "PMID:164664", "title": "Blue dextran-sepharose: an affinity column for the dinucleotide fold in proteins.", "content": "A procedure is described to utilize blue dextran-Sepharose as an affinity chromatographic column specific for the super-secondary structure called the dinucleotide fold, which forms the binding sites for substrates and effectors on a wide range of proteins. The procedure can be used to identify proteins, either purified or in crude cellular extracts, that possess the dinucleotide fold and to significantly improve the purification procedures for those proteins that possess the fold.", "contents": "Blue dextran-sepharose: an affinity column for the dinucleotide fold in proteins. A procedure is described to utilize blue dextran-Sepharose as an affinity chromatographic column specific for the super-secondary structure called the dinucleotide fold, which forms the binding sites for substrates and effectors on a wide range of proteins. The procedure can be used to identify proteins, either purified or in crude cellular extracts, that possess the dinucleotide fold and to significantly improve the purification procedures for those proteins that possess the fold."} {"id": "PMID:164665", "title": "Initiation and maintenance of cell transformation by simian virus 40: a viral genetic property.", "content": "The transforming ability in 10% serum medium of the temperature-sensitive mutants of simian virus 40 in the complementation group III (ts640 type mutants) was greatly reduced when the infected rat 3Y1 cells were incubated at the restrictive temperature of 40 degrees or incubated first at 40 degrees for 3 days and then shifted to the permissive temperature of 33 degrees. Transformation did occur efficiently after incubation at 33 degrees or after an initial incubation at 33 degrees for 5 days followed by a shift to 40 degrees. When growth properties of 3Y1 cells transformed at 33 degrees by the group III mutants were examined at 40 degrees, several aspects of the transformed state were rendered temperature-sensitive. These aspects were the ability of cells to grow in low serum (1.5%) medium and to make colonies, in 10% serum medium, on monolayers of untransformed 3Y1 cells and in soft agar. It is concluded that a simian virus 40 gene (cistron III) controls the initiation, as well as at least some aspects of the maintenance, of transformation and that the initiation reaction is a more heat-labile event than the maintenance reaction(s) under the experimental conditions.", "contents": "Initiation and maintenance of cell transformation by simian virus 40: a viral genetic property. The transforming ability in 10% serum medium of the temperature-sensitive mutants of simian virus 40 in the complementation group III (ts640 type mutants) was greatly reduced when the infected rat 3Y1 cells were incubated at the restrictive temperature of 40 degrees or incubated first at 40 degrees for 3 days and then shifted to the permissive temperature of 33 degrees. Transformation did occur efficiently after incubation at 33 degrees or after an initial incubation at 33 degrees for 5 days followed by a shift to 40 degrees. When growth properties of 3Y1 cells transformed at 33 degrees by the group III mutants were examined at 40 degrees, several aspects of the transformed state were rendered temperature-sensitive. These aspects were the ability of cells to grow in low serum (1.5%) medium and to make colonies, in 10% serum medium, on monolayers of untransformed 3Y1 cells and in soft agar. It is concluded that a simian virus 40 gene (cistron III) controls the initiation, as well as at least some aspects of the maintenance, of transformation and that the initiation reaction is a more heat-labile event than the maintenance reaction(s) under the experimental conditions."} {"id": "PMID:164666", "title": "Contact inhibition of phagocytosis in epithelial sheets: alterations of cell surface properties induced by cell-cell contacts.", "content": "Contact inhibition of phagocytosis was found to be characteristic for epithelial sheets formed in cultures by several cell types: normal and transformed mouse kidney cells, and differentiated mouse hepatoma cells. In these sheets most central cells surrounded by other cells had very low phagocytic activity. In contrast, marginal cells having a free edge were able to perform an active phagocytosis. Contact inhibition of phagocytosis was absent in dense cultures of mouse embryo fibroblasts and in cultures of anaplastic mouse hepatoma 22a. The upper surface of epithelial sheets was nonadhesive for prelabeled epithelial cells and fibroblasts. In contrast, the upper surface of dense cultures of mouse fibroblasts was adhesive for these cells. These and other data strengthen the suggestion that contact inhibition of phagocytosis is a result of different adhesiveness of the upper cell surface and of the surfaces near the free edge. Agents inhibiting cell surface movements at the free edges of marginal epithelial cells (cytochalasin, azide, sorbitol, low temperature) prevented adhesion of particles to these edges. Possibly, the surface of actively moving cytoplasmic processes is the only cell part that has adhesive properties necessary for the formation of attachments with other cellular and noncellular surfaces. In epithelial sheets, in contrast to fibroblast cultures, Colcemid did not activate movements of immobile contacting cell edges. These results indicate that mechanisms of contact immobilization of cell surface may be different in epithelium and fibroblasts. Firm contacts formed between epithelial cells are sufficient for stable immobilization of the surface; additional stabilization of the surface by microtubules is not essential. Fibroblasts do not form firm contacts and the Colcemid-sensitive stabilization process is essential for maintenance of the immobile state of their surfaces. Differences in the stability of cell surface immobilization produced by cell-cell contacts may also explain different adhesiveness of the upper surfaces of dense fibroblastic and epithelial cultures.", "contents": "Contact inhibition of phagocytosis in epithelial sheets: alterations of cell surface properties induced by cell-cell contacts. Contact inhibition of phagocytosis was found to be characteristic for epithelial sheets formed in cultures by several cell types: normal and transformed mouse kidney cells, and differentiated mouse hepatoma cells. In these sheets most central cells surrounded by other cells had very low phagocytic activity. In contrast, marginal cells having a free edge were able to perform an active phagocytosis. Contact inhibition of phagocytosis was absent in dense cultures of mouse embryo fibroblasts and in cultures of anaplastic mouse hepatoma 22a. The upper surface of epithelial sheets was nonadhesive for prelabeled epithelial cells and fibroblasts. In contrast, the upper surface of dense cultures of mouse fibroblasts was adhesive for these cells. These and other data strengthen the suggestion that contact inhibition of phagocytosis is a result of different adhesiveness of the upper cell surface and of the surfaces near the free edge. Agents inhibiting cell surface movements at the free edges of marginal epithelial cells (cytochalasin, azide, sorbitol, low temperature) prevented adhesion of particles to these edges. Possibly, the surface of actively moving cytoplasmic processes is the only cell part that has adhesive properties necessary for the formation of attachments with other cellular and noncellular surfaces. In epithelial sheets, in contrast to fibroblast cultures, Colcemid did not activate movements of immobile contacting cell edges. These results indicate that mechanisms of contact immobilization of cell surface may be different in epithelium and fibroblasts. Firm contacts formed between epithelial cells are sufficient for stable immobilization of the surface; additional stabilization of the surface by microtubules is not essential. Fibroblasts do not form firm contacts and the Colcemid-sensitive stabilization process is essential for maintenance of the immobile state of their surfaces. Differences in the stability of cell surface immobilization produced by cell-cell contacts may also explain different adhesiveness of the upper surfaces of dense fibroblastic and epithelial cultures."} {"id": "PMID:164667", "title": "Decrease in membrane-associated actin of fibroblasts after transformation by Rous sarcoma virus.", "content": "The actin content of membranes prepared from cultured chick embryo fibroblasts has been measured on polyacrylamide gels. The actin was identified by tryptic peptide mapping. After transformation of the cells by Rous sarcoma virus, the amount of actin associated with the membranes is decreased by 30-50%. This result is not due to infection per se, since infection by a temperature-sensitive strain of the virus decreases membrane-associated actin only at the permissive temperature. A shift from the nonpermissive (41 degrees) to the permissive (36 degrees) temperature results in an increase in the percentage of total cellular protein synthesis devoted to actin production, so that the decrease in membrane-associated actin appears to be a selective displacement from the membrane rather than a general decrease in total cellular actin.", "contents": "Decrease in membrane-associated actin of fibroblasts after transformation by Rous sarcoma virus. The actin content of membranes prepared from cultured chick embryo fibroblasts has been measured on polyacrylamide gels. The actin was identified by tryptic peptide mapping. After transformation of the cells by Rous sarcoma virus, the amount of actin associated with the membranes is decreased by 30-50%. This result is not due to infection per se, since infection by a temperature-sensitive strain of the virus decreases membrane-associated actin only at the permissive temperature. A shift from the nonpermissive (41 degrees) to the permissive (36 degrees) temperature results in an increase in the percentage of total cellular protein synthesis devoted to actin production, so that the decrease in membrane-associated actin appears to be a selective displacement from the membrane rather than a general decrease in total cellular actin."} {"id": "PMID:164668", "title": "Hamster alpha-amanitine-resistant RNA polymerase II able to transcribe polyoma virus genome in somatic cell hybrids.", "content": "A hamster cell line resistant to alpha-amanitine has been isolated (alpha-am-r, BHK-T6-G-1). Cell extracts of this mutant have an alpha-amanitine-resistant RNA polymerase II (nucleosidetriphosphate: RNA nucleotidyl-transferase, EC 2.7.7.6) activity as shown by DEAE-cellulose column chromatography. This mutation is dominant in interspecific hybrids with 3T3 mouse cells. In such hybrids polyoma virus can grow with equal efficiency in the presence or absence of the drug, thus indicating that the RNA polymerase of the unsusceptible parental cell can participate in the correct transcription of the viral genome.", "contents": "Hamster alpha-amanitine-resistant RNA polymerase II able to transcribe polyoma virus genome in somatic cell hybrids. A hamster cell line resistant to alpha-amanitine has been isolated (alpha-am-r, BHK-T6-G-1). Cell extracts of this mutant have an alpha-amanitine-resistant RNA polymerase II (nucleosidetriphosphate: RNA nucleotidyl-transferase, EC 2.7.7.6) activity as shown by DEAE-cellulose column chromatography. This mutation is dominant in interspecific hybrids with 3T3 mouse cells. In such hybrids polyoma virus can grow with equal efficiency in the presence or absence of the drug, thus indicating that the RNA polymerase of the unsusceptible parental cell can participate in the correct transcription of the viral genome."} {"id": "PMID:164669", "title": "A chick-embyo cell microtest for typing of Herpesvirus hominis (38531).", "content": "Oral type 1 and genital type 2 Herpesvirus hominis (HVH) strains demonstrate distinctive biological properties in primary chick embryo cells (PCE) cultivated in microtest plates. With this procedure four reference strains of known types and 106 clinical isolates were differentiated as type 1 or 2. The type 1 strains showed low efficiency of infection and either no cytopathic effect (CPE) or only an incomplete CPE characterized by uniform thinning of the cell sheet in test wells. Type 2 strains had a high efficiency of infection and with CPE characterized by patchy plaque-like lesions readily distinguished from CPE of type 1 strains. A 96% correlation (27/28) between the PCE microtyping and kinetic neutralization tests and a 94% correlation (60/64) between the PCE microtyping and immunofluorescence test was obtained. The microplate PCE test is a simple, clear-cut, and reliable procedure for the typing of HVH.", "contents": "A chick-embyo cell microtest for typing of Herpesvirus hominis (38531). Oral type 1 and genital type 2 Herpesvirus hominis (HVH) strains demonstrate distinctive biological properties in primary chick embryo cells (PCE) cultivated in microtest plates. With this procedure four reference strains of known types and 106 clinical isolates were differentiated as type 1 or 2. The type 1 strains showed low efficiency of infection and either no cytopathic effect (CPE) or only an incomplete CPE characterized by uniform thinning of the cell sheet in test wells. Type 2 strains had a high efficiency of infection and with CPE characterized by patchy plaque-like lesions readily distinguished from CPE of type 1 strains. A 96% correlation (27/28) between the PCE microtyping and kinetic neutralization tests and a 94% correlation (60/64) between the PCE microtyping and immunofluorescence test was obtained. The microplate PCE test is a simple, clear-cut, and reliable procedure for the typing of HVH."} {"id": "PMID:164670", "title": "Increase in hematocrit, hemoglobin and red cell mass in normal mice after treatment with cyclic AMP (38543).", "content": "Chronic treatment of normal mice with either dibutyryl cyclic AMP or erythropoietin produced elevations in the hematocrit, hemoglobin concentration and red cell mass when compared to these same hematological parameters in untreated mice. Dibutyryl cyclic AMP increased red cell mass by 46% while ESF treatment resulted in a 56% increase in red cell mass. These studies confirm earlier reports of the effects of cyclic AMP in increasing radioactive iron incorporation into red cells and further indicate that this change is associated with an absolute increase renal cyclic AMP concentrations probably stimulate erythropoiesis as a consequence of increased kidney production of erythropoietin.", "contents": "Increase in hematocrit, hemoglobin and red cell mass in normal mice after treatment with cyclic AMP (38543). Chronic treatment of normal mice with either dibutyryl cyclic AMP or erythropoietin produced elevations in the hematocrit, hemoglobin concentration and red cell mass when compared to these same hematological parameters in untreated mice. Dibutyryl cyclic AMP increased red cell mass by 46% while ESF treatment resulted in a 56% increase in red cell mass. These studies confirm earlier reports of the effects of cyclic AMP in increasing radioactive iron incorporation into red cells and further indicate that this change is associated with an absolute increase renal cyclic AMP concentrations probably stimulate erythropoiesis as a consequence of increased kidney production of erythropoietin."} {"id": "PMID:164671", "title": "Binding of human chorionic gonadotropin by rat ovarian slices: dependence on the functional state of the ovary (38571).", "content": "Ovarian receptors specific for hCG-LH can be induced by PMSG-ovine LH priming. The marked increase in binding activity was accompanied by a rise in ovarian progesterone concentration and preceded by ovarian weight increase. The high binding activity of heavily luteinized ovaries was followed by a decline to prepriming levels during luteolysis. The ovarian progesterone content was decreased simultaneously and no change in ovarian weight was evident. The data demonstrate that ovarian hCG binding activity undergoes variation which depends on the functional state of ovaries.", "contents": "Binding of human chorionic gonadotropin by rat ovarian slices: dependence on the functional state of the ovary (38571). Ovarian receptors specific for hCG-LH can be induced by PMSG-ovine LH priming. The marked increase in binding activity was accompanied by a rise in ovarian progesterone concentration and preceded by ovarian weight increase. The high binding activity of heavily luteinized ovaries was followed by a decline to prepriming levels during luteolysis. The ovarian progesterone content was decreased simultaneously and no change in ovarian weight was evident. The data demonstrate that ovarian hCG binding activity undergoes variation which depends on the functional state of ovaries."} {"id": "PMID:164672", "title": "Influence of altering total body sodium on angiotensin I systemic converting activity (38573)", "content": "Studies were carried out in the dog to determine the extent to which alterations in total body sodium influence the systemic conversion of angiotensin 1. When the animals were maintained on a high salt diet and DOCA, conversion of angiotensin I increased signifcantly and returned to control levels when a normal salt diet was provided. When another group of animals were provided a low salt diet and mercuhydrin, angiotensin I conversion decreased significantly, although returning the animals to a normal salt diet had no further influence upon conversion. These experiments indicate that there is a direct relationship between total body sodium and the systemic conversion angiotensin 1.", "contents": "Influence of altering total body sodium on angiotensin I systemic converting activity (38573). Studies were carried out in the dog to determine the extent to which alterations in total body sodium influence the systemic conversion of angiotensin 1. When the animals were maintained on a high salt diet and DOCA, conversion of angiotensin I increased signifcantly and returned to control levels when a normal salt diet was provided. When another group of animals were provided a low salt diet and mercuhydrin, angiotensin I conversion decreased significantly, although returning the animals to a normal salt diet had no further influence upon conversion. These experiments indicate that there is a direct relationship between total body sodium and the systemic conversion angiotensin 1."} {"id": "PMID:164673", "title": "Effect of diethylaminoethyl-dextran on the replication of a murine sarcoma (Moloney)-leukemia virus complex in mouse embryo cultures (38577).", "content": "Isolates of a sarcoma (Moloney)-leukemia virus complex prepared as cell-free extracts from mouse tumors showed no enhancement in infectivity by DEAE-D either in the sarcoma moiety measured by focus formation or in the leukemia moiety measured by XC cell assay. The sarcoma moiety was not enhanced by DEAE-D in MEM and modified McCoy's 5a media or when varying amounts of FCS and glutamine were included in the media. Progressive enhancement of viral infectivity by DEAE-D was found when the viral preparations were passaged serially in MEF cells. DEAE-D ALSO ENHANCED TUMOR FORMATION IN VIVO BY TISSUE CULTURE PASSAGED VIRUS.", "contents": "Effect of diethylaminoethyl-dextran on the replication of a murine sarcoma (Moloney)-leukemia virus complex in mouse embryo cultures (38577). Isolates of a sarcoma (Moloney)-leukemia virus complex prepared as cell-free extracts from mouse tumors showed no enhancement in infectivity by DEAE-D either in the sarcoma moiety measured by focus formation or in the leukemia moiety measured by XC cell assay. The sarcoma moiety was not enhanced by DEAE-D in MEM and modified McCoy's 5a media or when varying amounts of FCS and glutamine were included in the media. Progressive enhancement of viral infectivity by DEAE-D was found when the viral preparations were passaged serially in MEF cells. DEAE-D ALSO ENHANCED TUMOR FORMATION IN VIVO BY TISSUE CULTURE PASSAGED VIRUS."} {"id": "PMID:164674", "title": "Physical, chemical and morphologic dimensions of human hepatitis A virus strain CR326 (38578).", "content": "CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 nm spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, indentical 27 nm viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The bouyant density of the virus in CsCl was 1.34 and it was heat (60 degrees), ether and acid stable but was destroyed by heat (100 degrees), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.", "contents": "Physical, chemical and morphologic dimensions of human hepatitis A virus strain CR326 (38578). CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 nm spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, indentical 27 nm viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The bouyant density of the virus in CsCl was 1.34 and it was heat (60 degrees), ether and acid stable but was destroyed by heat (100 degrees), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus."} {"id": "PMID:164675", "title": "Demonstration of feline leukemia virus antibody in cats by passive hemagglutination (38583).", "content": "Two FeLV fractions from Sephadex G-150 gel filtration were used to sensitize RBC for the PHA test. When the cells were coated with the fraction from the second peak consisting mostly of a mojor gs antigen of FeLV, no antibodies could be detected either in hyperimmunized cat sera or sera from leukemic cats, whereas antibodies were readily detectable in immunized rabbits. Using cells coated with the first peak eluants or Tween-ether disrupted FeLV, PHA antibodies were detected in cat sera. There existed, however, one significant exception that a cat with the diagnosis of mast cell leukemia showed antibody against the second peak fraction. Little or no antibodies could be detected in cat sera by CF or gel-diffusion. There was some correlation between hemagglutinating antibodies and conglutinating complement absorbing antibodies, but these antibodies did seem to differ from neutralizing antibody.", "contents": "Demonstration of feline leukemia virus antibody in cats by passive hemagglutination (38583). Two FeLV fractions from Sephadex G-150 gel filtration were used to sensitize RBC for the PHA test. When the cells were coated with the fraction from the second peak consisting mostly of a mojor gs antigen of FeLV, no antibodies could be detected either in hyperimmunized cat sera or sera from leukemic cats, whereas antibodies were readily detectable in immunized rabbits. Using cells coated with the first peak eluants or Tween-ether disrupted FeLV, PHA antibodies were detected in cat sera. There existed, however, one significant exception that a cat with the diagnosis of mast cell leukemia showed antibody against the second peak fraction. Little or no antibodies could be detected in cat sera by CF or gel-diffusion. There was some correlation between hemagglutinating antibodies and conglutinating complement absorbing antibodies, but these antibodies did seem to differ from neutralizing antibody."} {"id": "PMID:164676", "title": "The renin-angiotensin system in rats made hypertensive by ligation of the kidney poles (38584).", "content": "The renin-angiotensin system was studied in experimental renal hypertension produced by ligation of the poles of the left kidney followed by contralateral nephrectomy. Plasma renin concentration of renin substrate was lower and that of angiotensin I converting enzyme was higher in hypertensive animals. The juxtaglomerular index decreased in the medial zone of the kidney, while heavily granulated areas appeared in the poles. Ligated kidneys of rats that remained normotensive showed juxtaglomerular indices intermediate between the control and the hypertensive rats. Differences in renal renin content between the groups correspond to those for the juxtaglomerular index, but were smaller. No differences between the experimental groups were observed in iso-renin content in the brain; however in all animals with ligated kidney poles, hypertensive or normotensive, there was a tendency for iso-renin in the adrenals, left ventricular myocardium, and especially aorta to be lower than in controls.", "contents": "The renin-angiotensin system in rats made hypertensive by ligation of the kidney poles (38584). The renin-angiotensin system was studied in experimental renal hypertension produced by ligation of the poles of the left kidney followed by contralateral nephrectomy. Plasma renin concentration of renin substrate was lower and that of angiotensin I converting enzyme was higher in hypertensive animals. The juxtaglomerular index decreased in the medial zone of the kidney, while heavily granulated areas appeared in the poles. Ligated kidneys of rats that remained normotensive showed juxtaglomerular indices intermediate between the control and the hypertensive rats. Differences in renal renin content between the groups correspond to those for the juxtaglomerular index, but were smaller. No differences between the experimental groups were observed in iso-renin content in the brain; however in all animals with ligated kidney poles, hypertensive or normotensive, there was a tendency for iso-renin in the adrenals, left ventricular myocardium, and especially aorta to be lower than in controls."} {"id": "PMID:164677", "title": "The renin and iso-renin-angiotensin system in rats with experimental pitutary tumors (38585).", "content": "Renin, iso-renin, angiotensin I. angiotensin-converting enzyme, and angiotensinases were measured in plasma and in various extrarenal tissues of rats. Despite complete suppression of plasma renin in rats bearing pituitary tumors iso-renin and all other components of the renin-angiotensin system were found to be at or above control concentrations. The results strongly suggest that there is local synthesis of iso-renin in extrarenal tissues.", "contents": "The renin and iso-renin-angiotensin system in rats with experimental pitutary tumors (38585). Renin, iso-renin, angiotensin I. angiotensin-converting enzyme, and angiotensinases were measured in plasma and in various extrarenal tissues of rats. Despite complete suppression of plasma renin in rats bearing pituitary tumors iso-renin and all other components of the renin-angiotensin system were found to be at or above control concentrations. The results strongly suggest that there is local synthesis of iso-renin in extrarenal tissues."} {"id": "PMID:164679", "title": "Effects of central dopaminergic blockade with primozide upon the EEG stages of sleep in man.", "content": "The effect of pimozide, a potent and specific blocker of central dopaminergic transmission, upon the sleep of man was studied in six healthy volunteers. Given at doses of 1 and 4 mg, which have clear central effects in humand. pimozide produced only minor changes in the EEG patterns of sleep. At these doses a slight and non-significant decrease in phase I sleep was observed, while phases W,II,III,IV and REM were not modified. No differences were noted between drug or post-treatment and control nights in total NREM sleep, total REM sleep, number of episodes of REM or total number of eye movements. An increase in REM sleep in the first REM period in the first drug night were the only statistically significant findings. If one accepts that central effects seen in man after pimozide given in conditions similar to those of this study are due to dopaminergic blockade, our results tend to suggest that dopamine is, at most, of rather minor importance in the physiology of sleep in man.", "contents": "Effects of central dopaminergic blockade with primozide upon the EEG stages of sleep in man. The effect of pimozide, a potent and specific blocker of central dopaminergic transmission, upon the sleep of man was studied in six healthy volunteers. Given at doses of 1 and 4 mg, which have clear central effects in humand. pimozide produced only minor changes in the EEG patterns of sleep. At these doses a slight and non-significant decrease in phase I sleep was observed, while phases W,II,III,IV and REM were not modified. No differences were noted between drug or post-treatment and control nights in total NREM sleep, total REM sleep, number of episodes of REM or total number of eye movements. An increase in REM sleep in the first REM period in the first drug night were the only statistically significant findings. If one accepts that central effects seen in man after pimozide given in conditions similar to those of this study are due to dopaminergic blockade, our results tend to suggest that dopamine is, at most, of rather minor importance in the physiology of sleep in man."} {"id": "PMID:164680", "title": "The effect of triazolam on the sleep of insomniacs.", "content": "The effects of three oral doses of bedtime triazolam (0.25 mg, 0.5 mg, and 1.0 mg) a new benzodiazepine, on the laboratory sleep of insomniacs were studied in a double blind design which used the following 14 consecutive night schedule: 1-4 placebo; 5-11 drug; 12-14 placebo. Effects on sleep were measured objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by screening physicals and questionnaires administered each morning and each evening and by a comparison of the prestudy vs. end-study physical exams and clinical lab tests. At the 0.5 mg dose triazolam significantly reduced several objective and subjective measures of insomnia. It had lesser effects at the 0.25 mg dose and equal or greater effects at 1.0 mg dose. There were no remarkable side or toxic effects at any dose.", "contents": "The effect of triazolam on the sleep of insomniacs. The effects of three oral doses of bedtime triazolam (0.25 mg, 0.5 mg, and 1.0 mg) a new benzodiazepine, on the laboratory sleep of insomniacs were studied in a double blind design which used the following 14 consecutive night schedule: 1-4 placebo; 5-11 drug; 12-14 placebo. Effects on sleep were measured objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by screening physicals and questionnaires administered each morning and each evening and by a comparison of the prestudy vs. end-study physical exams and clinical lab tests. At the 0.5 mg dose triazolam significantly reduced several objective and subjective measures of insomnia. It had lesser effects at the 0.25 mg dose and equal or greater effects at 1.0 mg dose. There were no remarkable side or toxic effects at any dose."} {"id": "PMID:164686", "title": "Quantitative determination of the abnormal lipoprotein of cholestasis, LP-X, in liver disease.", "content": "Quantitative determination of the abnormal plasma lipoprotein of cholestasis LP-X has been performed in 81 LP-X positive patients with different liver disorders. Great variations in the plasma concentration of LP-X were demonstrated both in the 45 patients with intrahepatic cholestasis (acute hepatitis, toxic hepatitis, primary biliary cirrhosis and cholangitis) and in the 36 patients with extrahepatic cholestasis (extrahepatic biliary obstruction by tumours and choledocholithiasis). The plasma concentratkons of LP-X in the patients with extrahepatic cholestasis (median 158 mg/100 ml) were significantly (psmaller than 0.001) higher than in the patients with intraphepatic cholestasis (median 25 mg/100 ml) was exceeded by 42% of the patients with extrahepatic biliary obstruction, and 33% of the patients with extrahepatic biliary obstruction, had LP-X LEVELS ABOVE 400 MG/100ML. The plasma concentration of LP-X was significantly correlated to the plasma activity of alkaline phosphatases and serum bilirubin, but seemed to be superior to these two parameters in the differentiation between intrahepatic and extrahepatic cholestasis. Plasma levels of LP-X above 400 mg/100 ml are highly indicative of extrahepatic biliary obstruction.", "contents": "Quantitative determination of the abnormal lipoprotein of cholestasis, LP-X, in liver disease. Quantitative determination of the abnormal plasma lipoprotein of cholestasis LP-X has been performed in 81 LP-X positive patients with different liver disorders. Great variations in the plasma concentration of LP-X were demonstrated both in the 45 patients with intrahepatic cholestasis (acute hepatitis, toxic hepatitis, primary biliary cirrhosis and cholangitis) and in the 36 patients with extrahepatic cholestasis (extrahepatic biliary obstruction by tumours and choledocholithiasis). The plasma concentratkons of LP-X in the patients with extrahepatic cholestasis (median 158 mg/100 ml) were significantly (psmaller than 0.001) higher than in the patients with intraphepatic cholestasis (median 25 mg/100 ml) was exceeded by 42% of the patients with extrahepatic biliary obstruction, and 33% of the patients with extrahepatic biliary obstruction, had LP-X LEVELS ABOVE 400 MG/100ML. The plasma concentration of LP-X was significantly correlated to the plasma activity of alkaline phosphatases and serum bilirubin, but seemed to be superior to these two parameters in the differentiation between intrahepatic and extrahepatic cholestasis. Plasma levels of LP-X above 400 mg/100 ml are highly indicative of extrahepatic biliary obstruction."} {"id": "PMID:164688", "title": "[Bone scintigraphy with 99m Tc pyrophosphate in neurology].", "content": "99MTc pyrophosphate has restored bone scintigraphy to the position of respectability it had lost with radiostrontium 85 and 87m, and it has rapidly become the method of choice for the detection of osteogenic hyperactivity. In cases of tumor the histologic disorder is frequently detected prior to the morphologic changes seen in X-ray pictures. The biophysical properties of 99mTc pyrophosphate provide high quality imaging of the skeleton. The scans or scintiphotos render possible a more sensitive and earlier diagnosis than radiography, though bone scanning does not of course supersede radiography. The two methods are complementary. In present day oncologic practice, however, bone scintigraphy with 99mTc pyrophosphate replaces to advantage the conventional radiographic \"bone survey\". In neurology the change is already appreciable and has proved its worth. In the light of results in 78 neurologic patients attention is drawn to the significant changes bone scintigraphy has brought about in diagnosis and therapeutic planning. The indications which have already emerged from this new method of nuclear neurology are tabulated, discussed and illustrated.", "contents": "[Bone scintigraphy with 99m Tc pyrophosphate in neurology]. 99MTc pyrophosphate has restored bone scintigraphy to the position of respectability it had lost with radiostrontium 85 and 87m, and it has rapidly become the method of choice for the detection of osteogenic hyperactivity. In cases of tumor the histologic disorder is frequently detected prior to the morphologic changes seen in X-ray pictures. The biophysical properties of 99mTc pyrophosphate provide high quality imaging of the skeleton. The scans or scintiphotos render possible a more sensitive and earlier diagnosis than radiography, though bone scanning does not of course supersede radiography. The two methods are complementary. In present day oncologic practice, however, bone scintigraphy with 99mTc pyrophosphate replaces to advantage the conventional radiographic \"bone survey\". In neurology the change is already appreciable and has proved its worth. In the light of results in 78 neurologic patients attention is drawn to the significant changes bone scintigraphy has brought about in diagnosis and therapeutic planning. The indications which have already emerged from this new method of nuclear neurology are tabulated, discussed and illustrated."} {"id": "PMID:164689", "title": "[Sclerosis of the intestinal lymphatic vessels].", "content": "Fibrosis of the intestinal lymphatic vessels, produced in one case by tuberculosis and, in the other, by appendicitis and peritonitis, caused blockage of the main lymphatic vessels causing, clinically, a protein-losing enteropathy similar to that noted in congenital lymphatic diseases of childhood. In the laboratory, there was noted a fall in serum protein, lipid and cholesterol. A fat absorption test was very abnormal showing a flat curve. During laparotomy, there was discovered on the small intestine, the same layout of lymph vessels, resembling a lace network, as that observed in congenital malformations. Intestinal lymphography showed considerable stasis of the opaque substance and absence of injection of the lymph vessels in the mesentery.", "contents": "[Sclerosis of the intestinal lymphatic vessels]. Fibrosis of the intestinal lymphatic vessels, produced in one case by tuberculosis and, in the other, by appendicitis and peritonitis, caused blockage of the main lymphatic vessels causing, clinically, a protein-losing enteropathy similar to that noted in congenital lymphatic diseases of childhood. In the laboratory, there was noted a fall in serum protein, lipid and cholesterol. A fat absorption test was very abnormal showing a flat curve. During laparotomy, there was discovered on the small intestine, the same layout of lymph vessels, resembling a lace network, as that observed in congenital malformations. Intestinal lymphography showed considerable stasis of the opaque substance and absence of injection of the lymph vessels in the mesentery."} {"id": "PMID:164690", "title": "[Botulism. Therapeutic management. Apropos of 36 cases].", "content": "Botulism is relatively common in the Vienne department as we have observed 36 cases over a peroid of 7 years. Other French cases, published over the last 10 years, included 10 to 19 cases in the largest series. In a total of 10 series, there were 105 cases. Botulism is caused, in most cases, by eating ham prepared on the farm. It gives rise to the usual clinical picture including paralysis of accommodation, dysphagia, digestive symptoms with abdominal pain and constipation and finally, bladder paralysis. The mild forms are fairly common. We did not observe any severe cases. Our patients were treated in two homogeneous series of 17 cases each ; two patients were given no treatment. Patients treated by sero-anatoxin therapy according to classical methods, evolved towards a cure within 21 days on average. Patients treated by sulfguanidin were cured within 24 days. This study permitted us to confirm that sero-anatoxin therapy is not essential. The disadvantages are the number of injections, the possibility of sometimes fatal hyper-sensitive reactions which, in the opinion of many authors, justifies routine cover with cortisone. This attitude does not seem to us justified owing to the usually benign nature of the botulism. The treatment with sulfaguanidin is well tolerated and is not of any risk to the patient.", "contents": "[Botulism. Therapeutic management. Apropos of 36 cases]. Botulism is relatively common in the Vienne department as we have observed 36 cases over a peroid of 7 years. Other French cases, published over the last 10 years, included 10 to 19 cases in the largest series. In a total of 10 series, there were 105 cases. Botulism is caused, in most cases, by eating ham prepared on the farm. It gives rise to the usual clinical picture including paralysis of accommodation, dysphagia, digestive symptoms with abdominal pain and constipation and finally, bladder paralysis. The mild forms are fairly common. We did not observe any severe cases. Our patients were treated in two homogeneous series of 17 cases each ; two patients were given no treatment. Patients treated by sero-anatoxin therapy according to classical methods, evolved towards a cure within 21 days on average. Patients treated by sulfguanidin were cured within 24 days. This study permitted us to confirm that sero-anatoxin therapy is not essential. The disadvantages are the number of injections, the possibility of sometimes fatal hyper-sensitive reactions which, in the opinion of many authors, justifies routine cover with cortisone. This attitude does not seem to us justified owing to the usually benign nature of the botulism. The treatment with sulfaguanidin is well tolerated and is not of any risk to the patient."} {"id": "PMID:164691", "title": "[Immunologic changes and infections in alcoholic cirrhosis].", "content": "The authors explored humoral and cellular immunity in 50 cases of alcoholic cirrhosis. The levels of the three serum immunoglobulins were greater than normal. IgM was significantly higher. The levels of antipolio antibodies (types I, II and III) were significantly higher in cirrhosis than in controls. The antistreptolysin and antistaphylolysin titers showed that the differences between levels found in cirrhosis and in controls were not significant. After taking the Sabin polio vaccine, variations in antipolio antibodies remained within normal limits, considering the high levels noted before taking the vaccine. Total serum complement was normal in 90% of the estimtions carried out. The results of the intradermal reactions were dissociated. Tuberculin skin tests were negative in 35% of cases of cirrhosis and in 14.3% of controls. In skin tests for candida and streptococcal antigen, differences between cirrhotics and controls were not significant. The absolute figure for blood lymphocytes per mm-3 was, in half the cases, less than normal.", "contents": "[Immunologic changes and infections in alcoholic cirrhosis]. The authors explored humoral and cellular immunity in 50 cases of alcoholic cirrhosis. The levels of the three serum immunoglobulins were greater than normal. IgM was significantly higher. The levels of antipolio antibodies (types I, II and III) were significantly higher in cirrhosis than in controls. The antistreptolysin and antistaphylolysin titers showed that the differences between levels found in cirrhosis and in controls were not significant. After taking the Sabin polio vaccine, variations in antipolio antibodies remained within normal limits, considering the high levels noted before taking the vaccine. Total serum complement was normal in 90% of the estimtions carried out. The results of the intradermal reactions were dissociated. Tuberculin skin tests were negative in 35% of cases of cirrhosis and in 14.3% of controls. In skin tests for candida and streptococcal antigen, differences between cirrhotics and controls were not significant. The absolute figure for blood lymphocytes per mm-3 was, in half the cases, less than normal."} {"id": "PMID:164692", "title": "[Epithelial cancer and monoclonal immunoglobulins].", "content": "The authors report 4 cases of carcinoma of the intestine, stomach, ovary and breast, association with monoclonal Ig. Clinical and laboratory analysis showed, in particular, that the immunoglobulin was present in small quantity and that there was no Bence-Jones protein in these 4 cases, that the bone marrow was little, or practically unmodified. The authors then discuss the nature, whether by chance or not, of this association the differential diagnosis with major monoclonal dysglobulinemia, e.g. myeloma or Waldenstr\u00f6m's disease, and the significance in a cancer patient, of the discovery of Igmc. According to the authors, although in a few cases the tumour may induce development of a clone secreting Igmc, usually carcinoma and Igmc are independent from one another and are due to a common mechanism : reduction in cell immunity, according to Burnet.", "contents": "[Epithelial cancer and monoclonal immunoglobulins]. The authors report 4 cases of carcinoma of the intestine, stomach, ovary and breast, association with monoclonal Ig. Clinical and laboratory analysis showed, in particular, that the immunoglobulin was present in small quantity and that there was no Bence-Jones protein in these 4 cases, that the bone marrow was little, or practically unmodified. The authors then discuss the nature, whether by chance or not, of this association the differential diagnosis with major monoclonal dysglobulinemia, e.g. myeloma or Waldenstr\u00f6m's disease, and the significance in a cancer patient, of the discovery of Igmc. According to the authors, although in a few cases the tumour may induce development of a clone secreting Igmc, usually carcinoma and Igmc are independent from one another and are due to a common mechanism : reduction in cell immunity, according to Burnet."} {"id": "PMID:164695", "title": "Radioimmunoassay: review of basic principles.", "content": "The development of radioimmunoassay by the late Solomon A. Berson and Rosalyn S. Yalow during the late 1950s represents a milestone in the history of the application of radionuclide methodology to biology and to medical investigation and practice. The method offers a technique to assay materials otherwise unmeasureable or detectable only with difficulty. Radioimmunoassay is based upon the competition between labeled and unlabeled antigen for specific antibody sites, forming antigen-antibody complexes. This reaction is described by the expression see journal for formula. At equilibirum, the radioactive complex (bound) is separated from the radioactive antigen (free). The B/F ratio is dependent upon the amount of nonradioactive antigen. Antigen concentration in unknown samples is determined by comparing the B/F ratio to the B/F ratios obtained by incubating varying amounts of known nonradioactive antigen with the same amount of antibody as in the unknown sample under similar assay conditions. Sensitivity of the order of 10-12 moles/liter may be achieved through the preparation and use of a labeled antigen of high specific activity and the production and selection of antisera with appropriately high affinity constants. Specificity is dependent upon the ability of the antiserum to recognize subtle structural features of the antigen molecule. The ability to conveniently assay large numbers of samples with good precision has led to the application of this technique to quantitate substances (such as steroids) already measurable but by more cumbersome methods. Since the initial description of competitive binding radioassay techniques, there have been numerous contributions to its further development, refinement, and application. This article reviews the conception and development of this invaluable contribution to our understanding of health and disease.", "contents": "Radioimmunoassay: review of basic principles. The development of radioimmunoassay by the late Solomon A. Berson and Rosalyn S. Yalow during the late 1950s represents a milestone in the history of the application of radionuclide methodology to biology and to medical investigation and practice. The method offers a technique to assay materials otherwise unmeasureable or detectable only with difficulty. Radioimmunoassay is based upon the competition between labeled and unlabeled antigen for specific antibody sites, forming antigen-antibody complexes. This reaction is described by the expression see journal for formula. At equilibirum, the radioactive complex (bound) is separated from the radioactive antigen (free). The B/F ratio is dependent upon the amount of nonradioactive antigen. Antigen concentration in unknown samples is determined by comparing the B/F ratio to the B/F ratios obtained by incubating varying amounts of known nonradioactive antigen with the same amount of antibody as in the unknown sample under similar assay conditions. Sensitivity of the order of 10-12 moles/liter may be achieved through the preparation and use of a labeled antigen of high specific activity and the production and selection of antisera with appropriately high affinity constants. Specificity is dependent upon the ability of the antiserum to recognize subtle structural features of the antigen molecule. The ability to conveniently assay large numbers of samples with good precision has led to the application of this technique to quantitate substances (such as steroids) already measurable but by more cumbersome methods. Since the initial description of competitive binding radioassay techniques, there have been numerous contributions to its further development, refinement, and application. This article reviews the conception and development of this invaluable contribution to our understanding of health and disease."} {"id": "PMID:164696", "title": "Radioimmunoassay of insulin.", "content": "The powerful nuclear medicine tool of radioimmunoassay was very rapidly developed because of the favorable properties of insulin in such a procedure. The current method of insulin immunoassay in our laboratory is described, with emphasis on the details of the separation of bound and free using talc tablets; emphasis is also given to the correction for tracer damage. The clinical usefulness of the insulin radioimmunoassay is somewhat less than had been anticipated, although its use as a research tool has had immeasurable impact upon the study of metabolism. The presence of proinsulin in plasma is a factor that has to be considered during the radioimmunoassay. Radioimmunoassays for the connecting peptide of proinsulin have also been developed. A preliminary evaluation of two radioimmunoassay kits is described.", "contents": "Radioimmunoassay of insulin. The powerful nuclear medicine tool of radioimmunoassay was very rapidly developed because of the favorable properties of insulin in such a procedure. The current method of insulin immunoassay in our laboratory is described, with emphasis on the details of the separation of bound and free using talc tablets; emphasis is also given to the correction for tracer damage. The clinical usefulness of the insulin radioimmunoassay is somewhat less than had been anticipated, although its use as a research tool has had immeasurable impact upon the study of metabolism. The presence of proinsulin in plasma is a factor that has to be considered during the radioimmunoassay. Radioimmunoassays for the connecting peptide of proinsulin have also been developed. A preliminary evaluation of two radioimmunoassay kits is described."} {"id": "PMID:164697", "title": "Radioimmunoassay of plasma renin activity.", "content": "Plasma renin activity is quantitated by measuring the rate of angiotensin generation during incubation of plasma renin with endogenous renin substrate. The angiotensin is quantitated by radioimmunoassay. Our studies indicate that the incubation step is best carried out in undiluted plasma at the pH optimum for renin (pH 5.7) in the presence of EDTA, neomycin, and DFP or PMSF. By using these conditions, incubation of low-renin samples can be prolonged for up to 18 hr, because angiotensinases and converting enzyme are completely inhibited. Accuracy is enhanced by prolongation of the incubation time, which results in more angiotensin and eliminates the need for blank subtraction. Incubation at pH 7.4 is disadvantageous because of lower rates of generation of angiotensin 1, because of the inability to maintain pH constant without addition of strong buffer, and because the incubation step cannot be prolonged beyond 3 hr. Dilution of plasma is undesirable because it results in a slower reaction rate due to dilution of both enzyme and substrate, and it is not possible to correct for the effect of substrate dilution. The radioimmunoassay of angiotensin I presents few unusual problems. The volume of plasma assayed should be 20 muI or less. If blank subtraction is used, antibodies should be screened to determine the extent to which they bind nonspecific substances in plasma, and then to ascertain whether the blank is entirely additive when angiotensin is added to it. Assay sensitivity is an important issue, since approximately 30 percent of patients with essential hypertension have subnormal plasma renin activity. In a study of three different commercial kits we found that many low-renin samples were undetectable and major fractions could not be discriminated with precision or consistency from normal renin samples. However, the incubation conditions can be easily modified, so that an 18-hr incubation can be utilized and then low-renin samples can be detected with the same degree of accuracy as those with normal plasma renin activity.", "contents": "Radioimmunoassay of plasma renin activity. Plasma renin activity is quantitated by measuring the rate of angiotensin generation during incubation of plasma renin with endogenous renin substrate. The angiotensin is quantitated by radioimmunoassay. Our studies indicate that the incubation step is best carried out in undiluted plasma at the pH optimum for renin (pH 5.7) in the presence of EDTA, neomycin, and DFP or PMSF. By using these conditions, incubation of low-renin samples can be prolonged for up to 18 hr, because angiotensinases and converting enzyme are completely inhibited. Accuracy is enhanced by prolongation of the incubation time, which results in more angiotensin and eliminates the need for blank subtraction. Incubation at pH 7.4 is disadvantageous because of lower rates of generation of angiotensin 1, because of the inability to maintain pH constant without addition of strong buffer, and because the incubation step cannot be prolonged beyond 3 hr. Dilution of plasma is undesirable because it results in a slower reaction rate due to dilution of both enzyme and substrate, and it is not possible to correct for the effect of substrate dilution. The radioimmunoassay of angiotensin I presents few unusual problems. The volume of plasma assayed should be 20 muI or less. If blank subtraction is used, antibodies should be screened to determine the extent to which they bind nonspecific substances in plasma, and then to ascertain whether the blank is entirely additive when angiotensin is added to it. Assay sensitivity is an important issue, since approximately 30 percent of patients with essential hypertension have subnormal plasma renin activity. In a study of three different commercial kits we found that many low-renin samples were undetectable and major fractions could not be discriminated with precision or consistency from normal renin samples. However, the incubation conditions can be easily modified, so that an 18-hr incubation can be utilized and then low-renin samples can be detected with the same degree of accuracy as those with normal plasma renin activity."} {"id": "PMID:164698", "title": "Physiologic consequences of hepatic lobectomy in man.", "content": "Replacement of glucose and albumin in ten patients after hepatic lobectomy shows that hypoglycemia and hypoalbuminemia, the two most common consequences of lobectomy in animals, can be prevented in man. Biosynthesis of protein, cholesterol, and prothrombin are reduced temporarily. In patients having emergency lobectomy, the serum bilirubin and glutamic oxaloacetic transaminase concentrations are statistically greater than in patients having elective lobectomy. Serum ammonia is not elevated and bromsulphalein excretion is normal after bilirubin returns to less than 1 mg/100 ml. Lactic dehydrogenase concentrations in serum are increased and fluctuate in the presence of sepsis or respiratory insufficiency: Mean creatine phosphokinase peaks at concentrations higher than those reported in acute myocardial infarction and returns to normal in three days. Compensatory hyperplasia of the residual lobe occurred in all patients.", "contents": "Physiologic consequences of hepatic lobectomy in man. Replacement of glucose and albumin in ten patients after hepatic lobectomy shows that hypoglycemia and hypoalbuminemia, the two most common consequences of lobectomy in animals, can be prevented in man. Biosynthesis of protein, cholesterol, and prothrombin are reduced temporarily. In patients having emergency lobectomy, the serum bilirubin and glutamic oxaloacetic transaminase concentrations are statistically greater than in patients having elective lobectomy. Serum ammonia is not elevated and bromsulphalein excretion is normal after bilirubin returns to less than 1 mg/100 ml. Lactic dehydrogenase concentrations in serum are increased and fluctuate in the presence of sepsis or respiratory insufficiency: Mean creatine phosphokinase peaks at concentrations higher than those reported in acute myocardial infarction and returns to normal in three days. Compensatory hyperplasia of the residual lobe occurred in all patients."} {"id": "PMID:164699", "title": "Somatic hybridization and oncogenesis; (Mechanism of formation of malignant tumors and metastases by the action of antilymphocytic serum).", "content": "The results of experiments carried out to test some of the consequences of the earlier general theory of oncogenesis, according to which the malignant tumor cell can arise as a result of somatic hybridization of cells of different organ- and tissue-specificity, are described. In the first series a tumor induced by cellophane film, was grafted into syngeneic and allogeneic mice, and antilymphocytic serum (ALS) was then injected. Metastases occurred only in allogeneic recipients receiving ALS. It was thus shown that the ability of cells of this particular tumor to metastasize is not a property inherent in its cells but is acquired by them as a result of interaction with the recipient organism. In the second series it was shown by two immunological methods that the cells of metastases arising under these conditions contain tissue compatibility antigens of donor and recipient origin, i. e., that they are somatic hybridsmin the third series skin from individuals of another strain was grafted on to mice and ALS was injected; hepatomas developed in 74% of these mice. The theory is used to explain several phenomena of carcinogenesis not explicable by other theories: the phenotypic nature of cell transformation, the causes and nature of the duration of the latent period of tumor development, the mechanism responsible for the ability of tumors to overcome the system of immunological defense, the mechanism of activation of endogeneous oncogenic viruses, etc. Finally an answer is given to the question: what is a tumor?", "contents": "Somatic hybridization and oncogenesis; (Mechanism of formation of malignant tumors and metastases by the action of antilymphocytic serum). The results of experiments carried out to test some of the consequences of the earlier general theory of oncogenesis, according to which the malignant tumor cell can arise as a result of somatic hybridization of cells of different organ- and tissue-specificity, are described. In the first series a tumor induced by cellophane film, was grafted into syngeneic and allogeneic mice, and antilymphocytic serum (ALS) was then injected. Metastases occurred only in allogeneic recipients receiving ALS. It was thus shown that the ability of cells of this particular tumor to metastasize is not a property inherent in its cells but is acquired by them as a result of interaction with the recipient organism. In the second series it was shown by two immunological methods that the cells of metastases arising under these conditions contain tissue compatibility antigens of donor and recipient origin, i. e., that they are somatic hybridsmin the third series skin from individuals of another strain was grafted on to mice and ALS was injected; hepatomas developed in 74% of these mice. The theory is used to explain several phenomena of carcinogenesis not explicable by other theories: the phenotypic nature of cell transformation, the causes and nature of the duration of the latent period of tumor development, the mechanism responsible for the ability of tumors to overcome the system of immunological defense, the mechanism of activation of endogeneous oncogenic viruses, etc. Finally an answer is given to the question: what is a tumor?"} {"id": "PMID:164700", "title": "The effect of natural oestrogens on coagulation.", "content": "A study was undertaken to assess the effect of natural oestrogen on the coagulation profile of menopausal women. Forty-five postmenopausal women were selected at random and treated with conjugated oestrogen (PREMARIN) FOR ONE YEAR. Blood samples were tested before treatment, at the end of 3 and 9 months' therapy, and 1 month after treatment had been suspended. Parameters studied included: fibrinogen; platelet count and aggregation; single-stage prothrombin time; kaolin partial thromboplastin time; factors v and x assays and euglobulin lysis time. The only statistically significant alteration noted was a depressant effect on the platelet count. The significance of this change is commented upon. For practical purposes, it may be concluded that treatment of a group of menopausal women with conjugated oestraogen for one year had no adverse effect on their coagulation mechanism.", "contents": "The effect of natural oestrogens on coagulation. A study was undertaken to assess the effect of natural oestrogen on the coagulation profile of menopausal women. Forty-five postmenopausal women were selected at random and treated with conjugated oestrogen (PREMARIN) FOR ONE YEAR. Blood samples were tested before treatment, at the end of 3 and 9 months' therapy, and 1 month after treatment had been suspended. Parameters studied included: fibrinogen; platelet count and aggregation; single-stage prothrombin time; kaolin partial thromboplastin time; factors v and x assays and euglobulin lysis time. The only statistically significant alteration noted was a depressant effect on the platelet count. The significance of this change is commented upon. For practical purposes, it may be concluded that treatment of a group of menopausal women with conjugated oestraogen for one year had no adverse effect on their coagulation mechanism."} {"id": "PMID:164704", "title": "Incidence of paramalignant disorders in bronchogenic carcinoma.", "content": "The incidence of paramalignant disorders was studied in 280 consecutive patients with early lung cancer confirmed histologically. The commonest disorders were weight loss exceeding 6.4 kg (30.7 percent of the series), finger clubbing (29 percent), fever (21.1 percent), and endocrinopathies (12.1 percent). Paramalignant diseases are common even in early lung cancer and all patients should have investigations for their detection.", "contents": "Incidence of paramalignant disorders in bronchogenic carcinoma. The incidence of paramalignant disorders was studied in 280 consecutive patients with early lung cancer confirmed histologically. The commonest disorders were weight loss exceeding 6.4 kg (30.7 percent of the series), finger clubbing (29 percent), fever (21.1 percent), and endocrinopathies (12.1 percent). Paramalignant diseases are common even in early lung cancer and all patients should have investigations for their detection."} {"id": "PMID:164707", "title": "Disordered cholinergic neurotransmission and dysautoregulation after acute cerebral infarction.", "content": "The possible role of displaced neurotransmitter acetylcholine (ACHh) in dysautoregulation was examined after experimental regional cerebral infarction was produced by occluding the middle cerebral artery (MCA) in babons. Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xenon using the gamma camera. Autoregulation was tested with metaraminol or angiotensin infusion and the autoregulation index (A.I.) was calculated. Acetylcholinesterase (ACHhE) was measured in brain tissue of noninfarcted and infarcted hemispheres. Cerebral arteriovenous (A-V) differences for cholinesterase (ChE) were also measured. Regional dysautoregulation was found in infarcted gray matter and correlated with increased AChE levels in the same zones of cortex and basal ganglia. The time course of onset of dysautoregulation correlated with increased ChE uptake by the brain. Intravenous infusion of the cholinergic neurotransmitter blocker, scopolamine, restored autoregulation to the ischemic zones. Autoregulation appears to be a myogenic reflex, influenced by neurogenic and metabolic mechanisms.", "contents": "Disordered cholinergic neurotransmission and dysautoregulation after acute cerebral infarction. The possible role of displaced neurotransmitter acetylcholine (ACHh) in dysautoregulation was examined after experimental regional cerebral infarction was produced by occluding the middle cerebral artery (MCA) in babons. Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xenon using the gamma camera. Autoregulation was tested with metaraminol or angiotensin infusion and the autoregulation index (A.I.) was calculated. Acetylcholinesterase (ACHhE) was measured in brain tissue of noninfarcted and infarcted hemispheres. Cerebral arteriovenous (A-V) differences for cholinesterase (ChE) were also measured. Regional dysautoregulation was found in infarcted gray matter and correlated with increased AChE levels in the same zones of cortex and basal ganglia. The time course of onset of dysautoregulation correlated with increased ChE uptake by the brain. Intravenous infusion of the cholinergic neurotransmitter blocker, scopolamine, restored autoregulation to the ischemic zones. Autoregulation appears to be a myogenic reflex, influenced by neurogenic and metabolic mechanisms."} {"id": "PMID:164730", "title": "Immunofluorescence detection of casein in human mammary dysplastic and neoplastic tissues.", "content": "To detect and localize casein in human mammary dysplastic and neoplastic tissues, an indirect immunofluorescence method has been devised. Anti-casein antibodies have been obtained from rabbits immunized with casein isolated from human milk. Cryostat sections post-fixed in alcohol and paraffin sections from routinely formalin-fixed tissues proved suitable. The immuno-fluorescence method revealed the presence of casein in epithelial cells in mammary dysplasia and in some, but not all, cases of carcinoma of the breast. Well differentiated (Grade I) carcinomas were shown to contain casein, mainly localized at the inner border of the epithelial cells; the milk protein was present also in cells metastatic in lymph nodes. In Paget's disease of the nipple, casein could be detected in neoplastic cells in the ducts and also in cells identifiable with the typical intra-epidermal Paget cells. This finding is evidence of a functional differentiation of Paget cells along lines proper to the mammary epithelium.", "contents": "Immunofluorescence detection of casein in human mammary dysplastic and neoplastic tissues. To detect and localize casein in human mammary dysplastic and neoplastic tissues, an indirect immunofluorescence method has been devised. Anti-casein antibodies have been obtained from rabbits immunized with casein isolated from human milk. Cryostat sections post-fixed in alcohol and paraffin sections from routinely formalin-fixed tissues proved suitable. The immuno-fluorescence method revealed the presence of casein in epithelial cells in mammary dysplasia and in some, but not all, cases of carcinoma of the breast. Well differentiated (Grade I) carcinomas were shown to contain casein, mainly localized at the inner border of the epithelial cells; the milk protein was present also in cells metastatic in lymph nodes. In Paget's disease of the nipple, casein could be detected in neoplastic cells in the ducts and also in cells identifiable with the typical intra-epidermal Paget cells. This finding is evidence of a functional differentiation of Paget cells along lines proper to the mammary epithelium."} {"id": "PMID:164731", "title": "Malignant mixed osteogenic tumours of the breast. An ultrastructural study of two cases.", "content": "Two cases of malignant mesodermic tumours of the human mammary gland with osteogenic and chondrogenic structures were analysed by optical and electronic microscopical means. One of them was associated with an adenocarcinoma of the gland. The histological pattern was similar to that of those cases previously examined under the optical microscope in the mammary gland and in extraskeletal osteogenic sarcomas of soft tissues. When investigated under the electron microscope, the chondroblasts possessed a highly developed RER in active synthesis with an amorphous material which contributed to the building up of the ground substance matrix of the tumorous cartilage. Osteoid fields with scattered osteoblasts appear throughout the tumorous stroma and were associated with calcium deposits. They were continuous with fibroblasts and mesenchymal undifferentiated cells of a very immature character. Giant cells of osteoclastic type were included within the mononucleated mesenchymal cells mimicking bone osteoclastoma. The presence of all these cell types suggests the existence of a common malignant origin, the stem cell being differentiated into epithelial carcinomatous and mesenchymal sarcomatous chondral and osteogenic tissues.", "contents": "Malignant mixed osteogenic tumours of the breast. An ultrastructural study of two cases. Two cases of malignant mesodermic tumours of the human mammary gland with osteogenic and chondrogenic structures were analysed by optical and electronic microscopical means. One of them was associated with an adenocarcinoma of the gland. The histological pattern was similar to that of those cases previously examined under the optical microscope in the mammary gland and in extraskeletal osteogenic sarcomas of soft tissues. When investigated under the electron microscope, the chondroblasts possessed a highly developed RER in active synthesis with an amorphous material which contributed to the building up of the ground substance matrix of the tumorous cartilage. Osteoid fields with scattered osteoblasts appear throughout the tumorous stroma and were associated with calcium deposits. They were continuous with fibroblasts and mesenchymal undifferentiated cells of a very immature character. Giant cells of osteoclastic type were included within the mononucleated mesenchymal cells mimicking bone osteoclastoma. The presence of all these cell types suggests the existence of a common malignant origin, the stem cell being differentiated into epithelial carcinomatous and mesenchymal sarcomatous chondral and osteogenic tissues."} {"id": "PMID:164732", "title": "[Intraepithelial filament bundles of the adult human kidney. Studies by light and electron microscopy and by diffraction analysis (author's transl)].", "content": "In studies of semi-thin sections of adult human kidney it is found that the structures formerly known as \"Basalreifen\" can be definitely related to basal cytoplasmic portions of the renal epithelium. Under the electron microscope they appear as bundles of filaments, usually having a width of 50-85 A. They are particularly well developed in the parietal layer of Bowman's capsule and are also present in the proximal and distal tubule where they are more abundant than in other parts of the nephron. The filament bundles proceed toward hemidesmosome-like structures at the basal border of the epithelia and sometimes contain dense bodies in the parietal capsular epithelium of the glomerulus; these bundles are probably responsible for local intra- and/or supravital protrusions of the cytoplasm. Findings in some diseased kidneys are also presented. Diffraction analysis of intrarenal vascular muscle cells and intraepithelial filament bundles gave comparable photographic records of the image structure spectrograms; it supports the assumption derived from the electron microscopic results that the intraepithelial filament bundles represent a contractile complex. However, the conclusiveness of image structure analysis in comparing the two biological objects is limited, as outlined in the discussion. With regard to renal function the significance of the intraepithelial filament bundles is still unclear. Periglomerular interstitial cells, which normally contain only narrow tracts of filaments in the periphery, had many of the characteristics of smooth muscle cells in a case of pyelonephritic renal cirrhosis. They are compared with myofibroblasts of a different origin.", "contents": "[Intraepithelial filament bundles of the adult human kidney. Studies by light and electron microscopy and by diffraction analysis (author's transl)]. In studies of semi-thin sections of adult human kidney it is found that the structures formerly known as \"Basalreifen\" can be definitely related to basal cytoplasmic portions of the renal epithelium. Under the electron microscope they appear as bundles of filaments, usually having a width of 50-85 A. They are particularly well developed in the parietal layer of Bowman's capsule and are also present in the proximal and distal tubule where they are more abundant than in other parts of the nephron. The filament bundles proceed toward hemidesmosome-like structures at the basal border of the epithelia and sometimes contain dense bodies in the parietal capsular epithelium of the glomerulus; these bundles are probably responsible for local intra- and/or supravital protrusions of the cytoplasm. Findings in some diseased kidneys are also presented. Diffraction analysis of intrarenal vascular muscle cells and intraepithelial filament bundles gave comparable photographic records of the image structure spectrograms; it supports the assumption derived from the electron microscopic results that the intraepithelial filament bundles represent a contractile complex. However, the conclusiveness of image structure analysis in comparing the two biological objects is limited, as outlined in the discussion. With regard to renal function the significance of the intraepithelial filament bundles is still unclear. Periglomerular interstitial cells, which normally contain only narrow tracts of filaments in the periphery, had many of the characteristics of smooth muscle cells in a case of pyelonephritic renal cirrhosis. They are compared with myofibroblasts of a different origin."} {"id": "PMID:164734", "title": "Red cell esterase D in studies of paternity cases in the United Kingdom.", "content": "The recently discovered genetic polymorphism of human red cell esterase D has been applied to 156 cases of disputed paternity, along with other well-established systems. The results indicate that esterase D is a useful additional genetic marker for use in paternity testing.", "contents": "Red cell esterase D in studies of paternity cases in the United Kingdom. The recently discovered genetic polymorphism of human red cell esterase D has been applied to 156 cases of disputed paternity, along with other well-established systems. The results indicate that esterase D is a useful additional genetic marker for use in paternity testing."} {"id": "PMID:164740", "title": "Unsuccessful trial of gene replacement in arginase deficiency.", "content": "The Shope virus following cutaneous inoculation produces skin papillomas in rabbits and induces a virus-coded arginase in the squameous epithelium of these papillomas. The only discernible effect of the virus inoculated intravenously in rabbits and other animals was a decrease of the serum arginine concentration. Intravenous injection in 3 hyperargininemic patients, however, did not influence the underlying metabolic disease.", "contents": "Unsuccessful trial of gene replacement in arginase deficiency. The Shope virus following cutaneous inoculation produces skin papillomas in rabbits and induces a virus-coded arginase in the squameous epithelium of these papillomas. The only discernible effect of the virus inoculated intravenously in rabbits and other animals was a decrease of the serum arginine concentration. Intravenous injection in 3 hyperargininemic patients, however, did not influence the underlying metabolic disease."} {"id": "PMID:164737", "title": "[Serological variants of type 1 parainfluenza viruses].", "content": "A comparative study of the antigenic properties of parainfluenza type 1 viruses revealed the existence of 2 serological variants among them. The expedience of using the reference and recent years of isolates of parainfluenza type 1 viruses for serodiagnosis was demonstrated. Highly immunogenic strains isolated in 1971 were selected for properation of hyperimmune sera. It is necessary for identification of new isolates of parainfluenza type 1 viruses to use antisera for strains isolated in recent years alongside with reference immune sera.", "contents": "[Serological variants of type 1 parainfluenza viruses]. A comparative study of the antigenic properties of parainfluenza type 1 viruses revealed the existence of 2 serological variants among them. The expedience of using the reference and recent years of isolates of parainfluenza type 1 viruses for serodiagnosis was demonstrated. Highly immunogenic strains isolated in 1971 were selected for properation of hyperimmune sera. It is necessary for identification of new isolates of parainfluenza type 1 viruses to use antisera for strains isolated in recent years alongside with reference immune sera."} {"id": "PMID:164741", "title": "[Isolation of intact liver parenchymal cells by a modified enzymatic method].", "content": "An enzymatic method is described for isolating intact parenchymal cells from rat livers. 3--4 g cells (wet weight) could be isolated from livers of rats weighing 180--230 g. After an in vitro preperfusion of 15 minutes with a Ca-free buffer, collagenase (200 mg/1) and calcium chloride (5.2 mmol/1) were added. Perfusion was continued for another 15 minutes at 37 degrees C. Micromorphological integrity of cell membranes was demonstrated by scanning electron microscopy. With regard to rates of gluconeogenesis and protein synthesis, parenchymal cells isolated according to our method were found to be superior to liver slices and cells isolated by other methods. Ratios of ATP/ADP (5.69) and of lactate/pyruvate (8.64) as parameters of the energetic situation and the redox state resp. were found within the physiological range. Integrity of cell surface receptors was proved by their sensitivity to epinephrine, glucagon and insulin. Glucagon (0.3 mumol/1) and epinephrine (1 mumol/1) and reduced glycogen deposition in hepatocytes of fasted rats by 84.9 % and 95.9 % resp. Both hormones stimulated glycogenolysis in parenchymal cells of fed rats to a similar extent. Urea synthesis was stimulated 29.5 % by glucagon (1 mumol/1), and inhibited 28.0 % by insulin (10 nmol/1). The stimulatory effect of glucagon (1 mumol/1) was abolished by insulin (10 nmol/1).", "contents": "[Isolation of intact liver parenchymal cells by a modified enzymatic method]. An enzymatic method is described for isolating intact parenchymal cells from rat livers. 3--4 g cells (wet weight) could be isolated from livers of rats weighing 180--230 g. After an in vitro preperfusion of 15 minutes with a Ca-free buffer, collagenase (200 mg/1) and calcium chloride (5.2 mmol/1) were added. Perfusion was continued for another 15 minutes at 37 degrees C. Micromorphological integrity of cell membranes was demonstrated by scanning electron microscopy. With regard to rates of gluconeogenesis and protein synthesis, parenchymal cells isolated according to our method were found to be superior to liver slices and cells isolated by other methods. Ratios of ATP/ADP (5.69) and of lactate/pyruvate (8.64) as parameters of the energetic situation and the redox state resp. were found within the physiological range. Integrity of cell surface receptors was proved by their sensitivity to epinephrine, glucagon and insulin. Glucagon (0.3 mumol/1) and epinephrine (1 mumol/1) and reduced glycogen deposition in hepatocytes of fasted rats by 84.9 % and 95.9 % resp. Both hormones stimulated glycogenolysis in parenchymal cells of fed rats to a similar extent. Urea synthesis was stimulated 29.5 % by glucagon (1 mumol/1), and inhibited 28.0 % by insulin (10 nmol/1). The stimulatory effect of glucagon (1 mumol/1) was abolished by insulin (10 nmol/1)."} {"id": "PMID:164742", "title": "[An enzymatic method for the isolation of tubules and cells from human kidney cortex].", "content": "The isolation of tubules and cells from human kidney cortex was realized by an enzymatic method. Tubules and cells were released from slices of kidney cortex by collagenase. The yield amounted to 80 % of the wet weight of incubated cortex slices. Thus numerous experiments with isolated tubules from one organ could be performed. Glucose production from different substrates was measured in order to test the biochemical integrity of the isolated cells. The highest rates of glucose formation were obtained with fructose as precursor. Glucose production was higher from lactate than from pyruvate. With proline and glutamine as substrates only small amounts of glucose were produced. Glucose formation from 10 mmol/1 pyruvate was linear with time up to 80 minutes. Ado-3':5'-P stimulated glucose formation at 10 mumolar concentration and inhibited gluconeogenesis at 1 mmolar, 0.1 mmolar and 1 mumolar concentrations.", "contents": "[An enzymatic method for the isolation of tubules and cells from human kidney cortex]. The isolation of tubules and cells from human kidney cortex was realized by an enzymatic method. Tubules and cells were released from slices of kidney cortex by collagenase. The yield amounted to 80 % of the wet weight of incubated cortex slices. Thus numerous experiments with isolated tubules from one organ could be performed. Glucose production from different substrates was measured in order to test the biochemical integrity of the isolated cells. The highest rates of glucose formation were obtained with fructose as precursor. Glucose production was higher from lactate than from pyruvate. With proline and glutamine as substrates only small amounts of glucose were produced. Glucose formation from 10 mmol/1 pyruvate was linear with time up to 80 minutes. Ado-3':5'-P stimulated glucose formation at 10 mumolar concentration and inhibited gluconeogenesis at 1 mmolar, 0.1 mmolar and 1 mumolar concentrations."} {"id": "PMID:164745", "title": "[Infectious allergy. XIV. Histochemical changes in redox enzymes in cells of the small intestine smooth muscle during sensitization with diphtheria exotoxin].", "content": "Administration to guinea pigs of 1/Dlm of diphtheria exotoxin twice at an interval of 1 and 24 hours, or once in a dose of 25/100 Dlm caused changes in the activity of the redox enzymes. The character of their changes in the animals to which the whole dose of the exotoxin was administered once or repeatedly was directly reverse: in the first case the activity of the enzymes was uniformly increased, and in the second--ununiformly depressed; besides, there was a marked disturbance of coordination between the enzymes. An increased sensitivity of the infectious allergy type following injection of low doses of diphtheria exotoxin was not accompanied by immunity formation. Specific antibodies against diphtheria exotoxin formed only in the organism of animals to which 1/100 Dlm of diphtheria toxin was injected once a day for 15 days, but in this case as well no immunity against diphtheria exotoxin was observed.", "contents": "[Infectious allergy. XIV. Histochemical changes in redox enzymes in cells of the small intestine smooth muscle during sensitization with diphtheria exotoxin]. Administration to guinea pigs of 1/Dlm of diphtheria exotoxin twice at an interval of 1 and 24 hours, or once in a dose of 25/100 Dlm caused changes in the activity of the redox enzymes. The character of their changes in the animals to which the whole dose of the exotoxin was administered once or repeatedly was directly reverse: in the first case the activity of the enzymes was uniformly increased, and in the second--ununiformly depressed; besides, there was a marked disturbance of coordination between the enzymes. An increased sensitivity of the infectious allergy type following injection of low doses of diphtheria exotoxin was not accompanied by immunity formation. Specific antibodies against diphtheria exotoxin formed only in the organism of animals to which 1/100 Dlm of diphtheria toxin was injected once a day for 15 days, but in this case as well no immunity against diphtheria exotoxin was observed."} {"id": "PMID:164746", "title": "[Ultrastructure of L-forms. II. L-forms of Listeria monocytogenes].", "content": "A study was made of ultrathin sections of the stable l-forms of listeria obtained under the action of penicillin in meat-peptone-liver broth. A marked cellular polymorphism was found in the L-form culture: within the same colony cells differed in size, shape and fine structure. It is supposed that polymorphism could be partially explained by a different plasticity and premeability of cytoplasmic membrane in different types of cells of the same L-colony. The three-layer structure of the membrane does not always display the same distinctness in various L-colony cells and also in different areas of the cell surface. Structureless material of low electron density, possibly a defective murein or its precursor, was revealed on the membrane surface. Electrondense inclusion bodies, mesosomes of ring-shaped or more complicated structure and two-contour vesicles were found in the cytoplasm. The cells multiplied by budding, by binary and anomalies division participation of mesosomes in this process was not proved by the L-forms.", "contents": "[Ultrastructure of L-forms. II. L-forms of Listeria monocytogenes]. A study was made of ultrathin sections of the stable l-forms of listeria obtained under the action of penicillin in meat-peptone-liver broth. A marked cellular polymorphism was found in the L-form culture: within the same colony cells differed in size, shape and fine structure. It is supposed that polymorphism could be partially explained by a different plasticity and premeability of cytoplasmic membrane in different types of cells of the same L-colony. The three-layer structure of the membrane does not always display the same distinctness in various L-colony cells and also in different areas of the cell surface. Structureless material of low electron density, possibly a defective murein or its precursor, was revealed on the membrane surface. Electrondense inclusion bodies, mesosomes of ring-shaped or more complicated structure and two-contour vesicles were found in the cytoplasm. The cells multiplied by budding, by binary and anomalies division participation of mesosomes in this process was not proved by the L-forms."} {"id": "PMID:164747", "title": "[Characteristics of the low molecular antigens of pertussis bacteria].", "content": "The authors elaborated a method of obtaining pertussis soluble antigenic complex by dialysis through the cellophane membrane against the physiological saline at a temperature of 4 degrees C. An antigen which was active in the passive hemagglutination and neutralization of antibodies tests was revealed in the dialyzate. The amount of this antigen in the dialyzate increased gradually up to the 7th day and then became stabilized. The serological activity of the antigen after evaportation increased 4-16 times. The results of the antibody neutralization test pointed to the presence in the dialysate of substances common to those contained in the 1a and 1Da fractions isolated from the pertussis bacteria with the aid of ammounium sulfate.", "contents": "[Characteristics of the low molecular antigens of pertussis bacteria]. The authors elaborated a method of obtaining pertussis soluble antigenic complex by dialysis through the cellophane membrane against the physiological saline at a temperature of 4 degrees C. An antigen which was active in the passive hemagglutination and neutralization of antibodies tests was revealed in the dialyzate. The amount of this antigen in the dialyzate increased gradually up to the 7th day and then became stabilized. The serological activity of the antigen after evaportation increased 4-16 times. The results of the antibody neutralization test pointed to the presence in the dialysate of substances common to those contained in the 1a and 1Da fractions isolated from the pertussis bacteria with the aid of ammounium sulfate."} {"id": "PMID:164748", "title": "[Biological properties of plasma-negative staphylococci isolated from patients in surgical departments].", "content": "A study was made of 111 strains of plasma-negative spathylococci isolated from the blood, pleural fluid, urine, and exudate of the abdominal cavity of 30 patients. The studies were carried out by 18 criteria. A variety of biological properties and signs characteristic of pathogenic staphylococci (hemolytic activity, anaerobic splitting of mannite, the presence of phosphatase, lysozyme, protease, alpha-toxin, fibrinolysin) were noted. A high resistance to tetracycline and penicillin was found in the strains isolated from the blood and the pleural cavity.", "contents": "[Biological properties of plasma-negative staphylococci isolated from patients in surgical departments]. A study was made of 111 strains of plasma-negative spathylococci isolated from the blood, pleural fluid, urine, and exudate of the abdominal cavity of 30 patients. The studies were carried out by 18 criteria. A variety of biological properties and signs characteristic of pathogenic staphylococci (hemolytic activity, anaerobic splitting of mannite, the presence of phosphatase, lysozyme, protease, alpha-toxin, fibrinolysin) were noted. A high resistance to tetracycline and penicillin was found in the strains isolated from the blood and the pleural cavity."} {"id": "PMID:164749", "title": "[Use of a synthetic medium for cultivating pathogenic anaerobes].", "content": "It was shown that a synthetic medium suggested by the authors earlier was useful for the growth and toxin formation of Cl. tetani, Cl. botulinum and Cl. perfringens, types B and E. A study of the character of growth and toxinogensis, microscopic examination of morphology of culture cells and results of passages showed the suggested synthetic medium to be of value; a possibility of its application for studying the nutrient requirements and the role of individual components of the nutrient media in the process of growth and toxinogenesis was also demonstrated.", "contents": "[Use of a synthetic medium for cultivating pathogenic anaerobes]. It was shown that a synthetic medium suggested by the authors earlier was useful for the growth and toxin formation of Cl. tetani, Cl. botulinum and Cl. perfringens, types B and E. A study of the character of growth and toxinogensis, microscopic examination of morphology of culture cells and results of passages showed the suggested synthetic medium to be of value; a possibility of its application for studying the nutrient requirements and the role of individual components of the nutrient media in the process of growth and toxinogenesis was also demonstrated."} {"id": "PMID:164750", "title": "[Comparative study of nutrient media for isolation of the agents of pertussis and parapertussis].", "content": "Taking into consideration literature data pointing to a possibility of a marked improvement of the quality of the medium for the isolation of the causative agents of pertussis and parapertussis, an experimental study was made of the sensitivity of the nutrient media produced by the Dagestan Institute of Nutrient Media, a medium made from dry and also of a number of media modified by the authors prepared on its basis. Pure freshly-isolated and museum B. pertussis cultures were used in the observations. Analysis of the results of a comparative study of the indices (detectability of the strains, the appearance of colonies and periods of their formation) allomed a recipee of the most sensitive medium to be elaborated. At the same time there were found considerable differences in the indices of the appearance of B. pertussis colonies and detectability of the museum cultures used for testing the industrial batches and of the freshly-isolated strains.", "contents": "[Comparative study of nutrient media for isolation of the agents of pertussis and parapertussis]. Taking into consideration literature data pointing to a possibility of a marked improvement of the quality of the medium for the isolation of the causative agents of pertussis and parapertussis, an experimental study was made of the sensitivity of the nutrient media produced by the Dagestan Institute of Nutrient Media, a medium made from dry and also of a number of media modified by the authors prepared on its basis. Pure freshly-isolated and museum B. pertussis cultures were used in the observations. Analysis of the results of a comparative study of the indices (detectability of the strains, the appearance of colonies and periods of their formation) allomed a recipee of the most sensitive medium to be elaborated. At the same time there were found considerable differences in the indices of the appearance of B. pertussis colonies and detectability of the museum cultures used for testing the industrial batches and of the freshly-isolated strains."} {"id": "PMID:164751", "title": "[The response of blood neutrophils (the PPN test) to pertussis allergen in children with pertussis and children immunized with ADPT vaccine].", "content": "The authors present materials on the study of the reaction of blood neutrophils (PPN test) to pertussis allergen in children suffering from pertussis and immunized with ADPT vaccine. Results obtained in examining 111 children showed that the PPN test was specific and could be used for assessment of allergic manifestations in children suffering from pertussis or immunized with ADPT vaccine. Taking into consideration the harmlessness and expressiveness of the PPN test it can be recommended for studying in dynamics in any age groups.", "contents": "[The response of blood neutrophils (the PPN test) to pertussis allergen in children with pertussis and children immunized with ADPT vaccine]. The authors present materials on the study of the reaction of blood neutrophils (PPN test) to pertussis allergen in children suffering from pertussis and immunized with ADPT vaccine. Results obtained in examining 111 children showed that the PPN test was specific and could be used for assessment of allergic manifestations in children suffering from pertussis or immunized with ADPT vaccine. Taking into consideration the harmlessness and expressiveness of the PPN test it can be recommended for studying in dynamics in any age groups."} {"id": "PMID:164754", "title": "New kind of cytoplasmic inclusions of plasma cells in acid maltase deficiency.", "content": "Extensive 'vacuolization' could be demonstrated in nearly all plasma cells and in some lymphocytes of an adult with glycogenosis type II (Pompe's disease). The biochemically defined diagnosis acid maltase deficiency (AMD) could be ascertained by examination of the maltase activity of the patient's leukocytes. Electron microscopical, microspectrographic, and cytochemical investigations revealed electron dense inclusions, which show an UV absorption at 276 nm and a positive reaction after PAS staining of plastic embedded material. Since no other abnormalities of the plasma cells could be found, our results are presumably indicative for a connection of AMD and a glycoprotein storage in the plasma cells of the patient.", "contents": "New kind of cytoplasmic inclusions of plasma cells in acid maltase deficiency. Extensive 'vacuolization' could be demonstrated in nearly all plasma cells and in some lymphocytes of an adult with glycogenosis type II (Pompe's disease). The biochemically defined diagnosis acid maltase deficiency (AMD) could be ascertained by examination of the maltase activity of the patient's leukocytes. Electron microscopical, microspectrographic, and cytochemical investigations revealed electron dense inclusions, which show an UV absorption at 276 nm and a positive reaction after PAS staining of plastic embedded material. Since no other abnormalities of the plasma cells could be found, our results are presumably indicative for a connection of AMD and a glycoprotein storage in the plasma cells of the patient."} {"id": "PMID:164755", "title": "Fenestrae in golgi and endoplasmic reticulum cisternae of human brain tumours.", "content": "Fenestrae were found in freeze-fractured cisternae of the Golgi apparatus and endoplasmic reticulum of glioblastoma, oligodendroglioma, ependymoma, medulloblastoma, medulloepithelioma, meningioma, cerebellar sarcoma, hemangioblastoma, and chromophobe adenoma. They were about 200--400 A in diameter and often diffusely distributed or concentrated in groups in Golgi cisternae, while they were around 300--600 A in size and scattered in distribution in cisternae of endoplasmic reticulum. They appeared as conical protrusions or circular broken-off necks of face A and as circular holes on face B in tangential fractures, and as several constrictions of cisternae in cross fractures.", "contents": "Fenestrae in golgi and endoplasmic reticulum cisternae of human brain tumours. Fenestrae were found in freeze-fractured cisternae of the Golgi apparatus and endoplasmic reticulum of glioblastoma, oligodendroglioma, ependymoma, medulloblastoma, medulloepithelioma, meningioma, cerebellar sarcoma, hemangioblastoma, and chromophobe adenoma. They were about 200--400 A in diameter and often diffusely distributed or concentrated in groups in Golgi cisternae, while they were around 300--600 A in size and scattered in distribution in cisternae of endoplasmic reticulum. They appeared as conical protrusions or circular broken-off necks of face A and as circular holes on face B in tangential fractures, and as several constrictions of cisternae in cross fractures."} {"id": "PMID:164756", "title": "Morphological observations of dysplastic gliomas heterotransplanted to experimental animals.", "content": "Observations concerning transplantation of 5 cases of malignant dysplastic gliomas to the anterior chamber of the guinea-pig eye have been presented. This type of gliomas, composed mainly of cytoplasm-abundant cells, show weak transplantability, slow rate of growth, and particular tendency to degeneration and necrosis. At the same time, in subsequent passages, an intensive proliferation of small-cell component occurs, comparing with cytoplasm-abundant cells.", "contents": "Morphological observations of dysplastic gliomas heterotransplanted to experimental animals. Observations concerning transplantation of 5 cases of malignant dysplastic gliomas to the anterior chamber of the guinea-pig eye have been presented. This type of gliomas, composed mainly of cytoplasm-abundant cells, show weak transplantability, slow rate of growth, and particular tendency to degeneration and necrosis. At the same time, in subsequent passages, an intensive proliferation of small-cell component occurs, comparing with cytoplasm-abundant cells."} {"id": "PMID:164757", "title": "Atypical astrocytes and Rosenthal fibers in a case of amyotrophic lateral sclerosis associated with a cerebral glioblastoma multiforme.", "content": "A case of amyotrophic lateral sclerosis (ALS) and cerebral glioblastoma multiforme is presented in which bizarre astrocytes were found in the degenerating lateral corticospinal tracts, along with Rosenthal fibers, which were present in the corticospinal tracts of the lower medulla and spinal cord, and in anterior horns. These bizarre astrocytes did not result from direct infiltration of tumor from the cerebrum. \"Malignant transformation\" and/or an exceptionally intense glial response to the corticospinal tract degeneration are discussed as possibilities for the development of these bizarre astrocytes. Rosenthal fiber formation is described, to our knowledge, for the first time in ALS.", "contents": "Atypical astrocytes and Rosenthal fibers in a case of amyotrophic lateral sclerosis associated with a cerebral glioblastoma multiforme. A case of amyotrophic lateral sclerosis (ALS) and cerebral glioblastoma multiforme is presented in which bizarre astrocytes were found in the degenerating lateral corticospinal tracts, along with Rosenthal fibers, which were present in the corticospinal tracts of the lower medulla and spinal cord, and in anterior horns. These bizarre astrocytes did not result from direct infiltration of tumor from the cerebrum. \"Malignant transformation\" and/or an exceptionally intense glial response to the corticospinal tract degeneration are discussed as possibilities for the development of these bizarre astrocytes. Rosenthal fiber formation is described, to our knowledge, for the first time in ALS."} {"id": "PMID:164758", "title": "Studies on the presence of antibodies to EB virus and other herpesviruses in normal children and in infectious mononucleosis.", "content": "Children free from infectious disease have been examined by indirect immunofluorescence for the presence of antibodies to the intracellular capsid antigen of Epstein-Barr virus (EBV). In the first year of life 46%, between 2 and 6 years of age 66%, and between 7 and 14 years 91%, of the children proved positive. The corresponding percentages for the presence of antibodies to cytomegalovirus (CMV) and herpes simplex virus were about 50%, irrespective of the children's age. Serum samples from 69 patients suffering from infectious mononucleosis (IM) were tested for anti-EBV antibodies. Of the 29 Paul-Bunnell-positive patients 22 had antibodies, 11 of them in high titres (greater than 1 : 80). Of the 40 Paul-Bunnell-negative cases only 21 had antibodies, 8 in high titres. Of the Paul-Bunnell-negative cases, 73% were found to have anti-CMV antibodies, 32% in high titre. The respective percentages for the Paul-Bunnell-positive cases were 42% and 10%.", "contents": "Studies on the presence of antibodies to EB virus and other herpesviruses in normal children and in infectious mononucleosis. Children free from infectious disease have been examined by indirect immunofluorescence for the presence of antibodies to the intracellular capsid antigen of Epstein-Barr virus (EBV). In the first year of life 46%, between 2 and 6 years of age 66%, and between 7 and 14 years 91%, of the children proved positive. The corresponding percentages for the presence of antibodies to cytomegalovirus (CMV) and herpes simplex virus were about 50%, irrespective of the children's age. Serum samples from 69 patients suffering from infectious mononucleosis (IM) were tested for anti-EBV antibodies. Of the 29 Paul-Bunnell-positive patients 22 had antibodies, 11 of them in high titres (greater than 1 : 80). Of the 40 Paul-Bunnell-negative cases only 21 had antibodies, 8 in high titres. Of the Paul-Bunnell-negative cases, 73% were found to have anti-CMV antibodies, 32% in high titre. The respective percentages for the Paul-Bunnell-positive cases were 42% and 10%."} {"id": "PMID:164759", "title": "Factors influencing the stability of acid-precipitated polyvalent Bordetella pertussis bulk suspensions.", "content": "According to the statistical analysis of the potency values of acid precipitated polyvalent bulk suspensions of Bordetella pertussis, the potency of suspensions decreased below 8 IU/30 IOU during storage for 5 to 9.8 years. The average annual decrease over a 13-year period was 2.03 IU/30 IOU. The periodicity in the decrease of potency values was assumed to be connected with changes in the quality of the casein hydrolysate ingredient of the medium. Periodic functions employed to approach potency values with limits of 1 SD falling within the range of 64--156% indicated that the potency decreased below 8 IU/30 IOU after 9 years.", "contents": "Factors influencing the stability of acid-precipitated polyvalent Bordetella pertussis bulk suspensions. According to the statistical analysis of the potency values of acid precipitated polyvalent bulk suspensions of Bordetella pertussis, the potency of suspensions decreased below 8 IU/30 IOU during storage for 5 to 9.8 years. The average annual decrease over a 13-year period was 2.03 IU/30 IOU. The periodicity in the decrease of potency values was assumed to be connected with changes in the quality of the casein hydrolysate ingredient of the medium. Periodic functions employed to approach potency values with limits of 1 SD falling within the range of 64--156% indicated that the potency decreased below 8 IU/30 IOU after 9 years."} {"id": "PMID:164763", "title": "Managing ischemic skin ulcers.", "content": "Etiologic elements in ischemic ulcers include physical factors (pressure, shearing forces, friction and heat), nutrition and infection, as well as circulatory, metabolic and neurologic problems. Prevention is the primary objective of the management program. For patients in nursing homes who have already developed ulcers, low-intensity direct electric current (LIDC) has proved to be a useful adjunct to conventional management. The infection was more rapidly controlled and the wound size more quickly reduced. LIDC is readily accepted by the patient.", "contents": "Managing ischemic skin ulcers. Etiologic elements in ischemic ulcers include physical factors (pressure, shearing forces, friction and heat), nutrition and infection, as well as circulatory, metabolic and neurologic problems. Prevention is the primary objective of the management program. For patients in nursing homes who have already developed ulcers, low-intensity direct electric current (LIDC) has proved to be a useful adjunct to conventional management. The infection was more rapidly controlled and the wound size more quickly reduced. LIDC is readily accepted by the patient."} {"id": "PMID:164764", "title": "An unusual membrane-bound body in rat periosteal cells.", "content": "Cytoplasmic inclusions have been found in both normal and stimulated rat periosteal cells. These inclusions are bounded by a pentilaminar membrane similar to a tight junction and contain a core of granular material. The origin and function of this inclusion are unknown.", "contents": "An unusual membrane-bound body in rat periosteal cells. Cytoplasmic inclusions have been found in both normal and stimulated rat periosteal cells. These inclusions are bounded by a pentilaminar membrane similar to a tight junction and contain a core of granular material. The origin and function of this inclusion are unknown."} {"id": "PMID:164765", "title": "Passage of red blood cells through the sinusoidal wall of the spleen.", "content": "The migration of blood cells across the wall of splenic sinusoids has been studied by means of serial sections in rats inoculated with murine erythroblastosis virus (MEV). The sinusoidal walls of the normal spleen have no permanent openings. In the normal spleen, mature red blood cells and blood cells in the latest stages of maturation can be seen in diapedesis. The predominant form of transmural migration is intercellular. In MEV-inoculated animals, in which there is a vigorous erythroblastic proliferation, large numbers of erythroblasts are in transmural passage. Serial sections show that these cells migrate through the cytoplasm of the endothelial lining cells. On the basis of these observations, it is suggested that the transcellular mode of migration may be related to the delivery of newly formed red blood cells into the circulation while the intercellular mode may be part of the mechanism by which the spleen controls the removal of red cells from the circulation.", "contents": "Passage of red blood cells through the sinusoidal wall of the spleen. The migration of blood cells across the wall of splenic sinusoids has been studied by means of serial sections in rats inoculated with murine erythroblastosis virus (MEV). The sinusoidal walls of the normal spleen have no permanent openings. In the normal spleen, mature red blood cells and blood cells in the latest stages of maturation can be seen in diapedesis. The predominant form of transmural migration is intercellular. In MEV-inoculated animals, in which there is a vigorous erythroblastic proliferation, large numbers of erythroblasts are in transmural passage. Serial sections show that these cells migrate through the cytoplasm of the endothelial lining cells. On the basis of these observations, it is suggested that the transcellular mode of migration may be related to the delivery of newly formed red blood cells into the circulation while the intercellular mode may be part of the mechanism by which the spleen controls the removal of red cells from the circulation."} {"id": "PMID:164767", "title": "Plasma alpha-lipoprotein pattern in acute viral hepatitis.", "content": "In the present study, the plasma levels of lipoproteins, triglycerides, and cholesterol were followed serially in a group of 57 patients with acute viral hepatitis. Mean plasma triglyceride levels were found elevated at the onset of the disease and gradually returned to normal, while mean plasma cholesterol values, low initially, gradually increased, alpha-lipoprotein was absent at the early stage of hepatitis in 41 out of 46 patients with mild or moderate course and reappeared gradually during the course of the disease. In 11 cases of viral hepatitis with impending or overt coma, alpha-lipoprotein was absent for the whole duration of the acute stage and never reappeared in those who eventually died, while it eventually returned to normal in those who survived. The reappearance of alpha-lipoprotein in acute viral hepatitis appears to be a sensitive index of improvement and a significant prognostic sign.", "contents": "Plasma alpha-lipoprotein pattern in acute viral hepatitis. In the present study, the plasma levels of lipoproteins, triglycerides, and cholesterol were followed serially in a group of 57 patients with acute viral hepatitis. Mean plasma triglyceride levels were found elevated at the onset of the disease and gradually returned to normal, while mean plasma cholesterol values, low initially, gradually increased, alpha-lipoprotein was absent at the early stage of hepatitis in 41 out of 46 patients with mild or moderate course and reappeared gradually during the course of the disease. In 11 cases of viral hepatitis with impending or overt coma, alpha-lipoprotein was absent for the whole duration of the acute stage and never reappeared in those who eventually died, while it eventually returned to normal in those who survived. The reappearance of alpha-lipoprotein in acute viral hepatitis appears to be a sensitive index of improvement and a significant prognostic sign."} {"id": "PMID:164768", "title": "Acute respiratory disease of university students with special reference to the etiologic role of Herpesvirus hominis.", "content": "Infections with Herpesvirus hominis type 1 were associated with 11.5% of acute respiratory illnesses of university students who were admitted to the student infirmary over a 6-year period. Over three-quarters of these infections were detected in students with pharyngitis or tonsillitis; 42% had ulcerated lesions on tonsils or posterior pharynx but only 11% had lesions in the anterior portion of the mouth or lips. Almost all of the H. hominis infections were accompanied by significant rises in neutralizing antibodies and few students had detectable antibodies in the initial serum collected during the acute phase of illness. Special studies revealed herpes-specific IgM antibodies in the early convalescent sera of some of these patients. The data demonstrate that 80% of the infections detected were primary infections with H. hominis. Only 30% of university students possessed neutralizing antibodies to H. hominis and about 10% of those without antibodies acquired antibodies each year. These data suggest that the majority of persons from middle income families reach young adulthood without acquiring infections of H. hominis and the spread of the virus requires close and intimate contact.", "contents": "Acute respiratory disease of university students with special reference to the etiologic role of Herpesvirus hominis. Infections with Herpesvirus hominis type 1 were associated with 11.5% of acute respiratory illnesses of university students who were admitted to the student infirmary over a 6-year period. Over three-quarters of these infections were detected in students with pharyngitis or tonsillitis; 42% had ulcerated lesions on tonsils or posterior pharynx but only 11% had lesions in the anterior portion of the mouth or lips. Almost all of the H. hominis infections were accompanied by significant rises in neutralizing antibodies and few students had detectable antibodies in the initial serum collected during the acute phase of illness. Special studies revealed herpes-specific IgM antibodies in the early convalescent sera of some of these patients. The data demonstrate that 80% of the infections detected were primary infections with H. hominis. Only 30% of university students possessed neutralizing antibodies to H. hominis and about 10% of those without antibodies acquired antibodies each year. These data suggest that the majority of persons from middle income families reach young adulthood without acquiring infections of H. hominis and the spread of the virus requires close and intimate contact."} {"id": "PMID:164769", "title": "The Seattle virus watch. V. Epidemiologic observations of rhinovirus infections, 1965-1969, in families with young children.", "content": "Rhinovirus (RV) infections in Seattle Virus Watch (VW) families (1965-1969) were monitored by screening respiratory specimens in WI-38 cell cultures and by homotypic neutralization tests on sera related to family episodes revealed by RV isolation. Temporally related illness in members not proven infected was also taken to indicate infection. RV isolates (including those from the New York VW, 1961-1965) were typed within the official 90-serotype frame. Typed isolates from New York (165 with 39 serotypes) and Seattle (456 with 59 serotypes) were compared with the Tecumseh Study to test the hypothesis that some serotypes are \"common,\" persisting because of greater infectivity. Of 32 serotypes qualifying as \"common\" in at least 1 study, 4 were \"common\" in all 3 studies and 8 in 2 studies. The 23 \"common\" Seattle serotypes differed from the remaining 36 serotypes in being more infective and in their more frequent association with prolonged shedding. The New York and Seattle isolates together revealed an increase over time in the proportion not typable or of of higher numbered types, consistent with progressive shift in RV antigenic character. WI-38 isolates indicated spring peaks of RV all 4 years but a fall peak only in 1967. An even larger fall peak was seen when all specimens from September-November 1968 were re-examined in fetal tonsil diploid cells. Thus, both spring and fall peaks appear to describe RV seasonality. RV infections explained 16% of all reported respiratory illness (20% of upper respiratory), but RV-associated illness in young children, especially under 2 years, was more severe and almost twice as frequent as in adults. The age of introducers and the direct relation of family size to frequency of episodes indicate that community spread depends largely on preschool children, including infants. Within families, the secondary attack rate (SAR) was highest following paternal introduction and, for all introducers, the SAR varied inversely with age (mother excepted). RV shedding was observed most often (85% of specimens) from the day before to 6 days after illness onset but prolonged shedding was common (to 21 days in 20% and 28 days in 1.4% of infections). RV infectivity, reflected by SAR among nonimmunes, was highest for infants (78%) and, for all ages, was greater with ill than with well introducers (71% versus 27%). Immunogenicity of RV was poor (Seroresponse: 48% of shedders, 32% of nonshedding contacts) but varied greatly with serotype. Illness frequencies among non-immunes were 59% for all proven infections and 35% when infection was not shown..", "contents": "The Seattle virus watch. V. Epidemiologic observations of rhinovirus infections, 1965-1969, in families with young children. Rhinovirus (RV) infections in Seattle Virus Watch (VW) families (1965-1969) were monitored by screening respiratory specimens in WI-38 cell cultures and by homotypic neutralization tests on sera related to family episodes revealed by RV isolation. Temporally related illness in members not proven infected was also taken to indicate infection. RV isolates (including those from the New York VW, 1961-1965) were typed within the official 90-serotype frame. Typed isolates from New York (165 with 39 serotypes) and Seattle (456 with 59 serotypes) were compared with the Tecumseh Study to test the hypothesis that some serotypes are \"common,\" persisting because of greater infectivity. Of 32 serotypes qualifying as \"common\" in at least 1 study, 4 were \"common\" in all 3 studies and 8 in 2 studies. The 23 \"common\" Seattle serotypes differed from the remaining 36 serotypes in being more infective and in their more frequent association with prolonged shedding. The New York and Seattle isolates together revealed an increase over time in the proportion not typable or of of higher numbered types, consistent with progressive shift in RV antigenic character. WI-38 isolates indicated spring peaks of RV all 4 years but a fall peak only in 1967. An even larger fall peak was seen when all specimens from September-November 1968 were re-examined in fetal tonsil diploid cells. Thus, both spring and fall peaks appear to describe RV seasonality. RV infections explained 16% of all reported respiratory illness (20% of upper respiratory), but RV-associated illness in young children, especially under 2 years, was more severe and almost twice as frequent as in adults. The age of introducers and the direct relation of family size to frequency of episodes indicate that community spread depends largely on preschool children, including infants. Within families, the secondary attack rate (SAR) was highest following paternal introduction and, for all introducers, the SAR varied inversely with age (mother excepted). RV shedding was observed most often (85% of specimens) from the day before to 6 days after illness onset but prolonged shedding was common (to 21 days in 20% and 28 days in 1.4% of infections). RV infectivity, reflected by SAR among nonimmunes, was highest for infants (78%) and, for all ages, was greater with ill than with well introducers (71% versus 27%). Immunogenicity of RV was poor (Seroresponse: 48% of shedders, 32% of nonshedding contacts) but varied greatly with serotype. Illness frequencies among non-immunes were 59% for all proven infections and 35% when infection was not shown.."} {"id": "PMID:164770", "title": "Seroimmunity to poliomyelitis in an American community.", "content": "In an effort to determine the immune status of individuals in a natural community, neutralizing antibody titers for the three types of poliovirus were examined in 301 randomly sampled sera collected in 1966 and 308 specimens from 1971. The specimens were part of a larger collection obtained from residents of Tecumseh, Michigan. Approximately 22 sera from each five-year age group between 5-70 years were tested. A somewhat smaller number from younger and older individuals were also studied. Geometric mean titers for the two years of collection were in general quite low and never exceeded 1:42 which was found for type II virus. All GM titers decreased markedly as the age of the subjects increased. The percentage of individuals lacking antibody at the 1:4 level to at least one type of poliovirus ranged between 20-30% until age 49 and then steadily increased to over 60% in the 60-69 and over 70-year groups. A retrospective history of vaccination was obtained from 264 of the 308 persons in the 1971 collection. As expected these showed rather poor correlation with the presence or absence of antibody and were considered to be unsatisfactory as an index of immunity.", "contents": "Seroimmunity to poliomyelitis in an American community. In an effort to determine the immune status of individuals in a natural community, neutralizing antibody titers for the three types of poliovirus were examined in 301 randomly sampled sera collected in 1966 and 308 specimens from 1971. The specimens were part of a larger collection obtained from residents of Tecumseh, Michigan. Approximately 22 sera from each five-year age group between 5-70 years were tested. A somewhat smaller number from younger and older individuals were also studied. Geometric mean titers for the two years of collection were in general quite low and never exceeded 1:42 which was found for type II virus. All GM titers decreased markedly as the age of the subjects increased. The percentage of individuals lacking antibody at the 1:4 level to at least one type of poliovirus ranged between 20-30% until age 49 and then steadily increased to over 60% in the 60-69 and over 70-year groups. A retrospective history of vaccination was obtained from 264 of the 308 persons in the 1971 collection. As expected these showed rather poor correlation with the presence or absence of antibody and were considered to be unsatisfactory as an index of immunity."} {"id": "PMID:164771", "title": "Familial occurrence of Wilms' tumor: nephroblastoma in one of monozygous twins and in another sibling.", "content": "We report the occurrence of pathologically documented Wilm's tumor in a 24-month-old male twin and just 9 months later in his 12-month-old male sibling. We considered the twins to be monozygotic because of their phenotypic similarities, the probability computed from analysis of blood groups, and the comparison of their dermatoglphics. There were no other persons in the kindred with either tumor or associated malformations, and the parents were not consanguineous. Because of the frequency of Wilm's tumor, the few instances of demonstrated occurrence in siblings seem insufficient to postulate monogenic determination. Concordance in monozygotic twins has simply not been proven. The monozygotic unaffected twin of our first patient has remained without evidence of tumor to 5 years, and, as long as he remains so, he appears to represent an exception to the hypothesis of the mutagenic origin of this childhood tumor.", "contents": "Familial occurrence of Wilms' tumor: nephroblastoma in one of monozygous twins and in another sibling. We report the occurrence of pathologically documented Wilm's tumor in a 24-month-old male twin and just 9 months later in his 12-month-old male sibling. We considered the twins to be monozygotic because of their phenotypic similarities, the probability computed from analysis of blood groups, and the comparison of their dermatoglphics. There were no other persons in the kindred with either tumor or associated malformations, and the parents were not consanguineous. Because of the frequency of Wilm's tumor, the few instances of demonstrated occurrence in siblings seem insufficient to postulate monogenic determination. Concordance in monozygotic twins has simply not been proven. The monozygotic unaffected twin of our first patient has remained without evidence of tumor to 5 years, and, as long as he remains so, he appears to represent an exception to the hypothesis of the mutagenic origin of this childhood tumor."} {"id": "PMID:164772", "title": "Hypogonadism in Prader-Willi syndrome.", "content": "Sexual development was evaluated in 9 female and 2 male subjects with Prader-Willi syndrome. The process of sexual development and degree of genital development attained were found to be variable but abnormal in all subjects. Hypothalamic-pituitary-gonadal functions were evaluated by measurement of serum Luteinizing Hormone and plasma testosterone responses to stimulation by clomiphene citrate and plasma testosterone responses to stimulation by human chorionic gonadotrophin. The degree of vaginal estrogenization was variable. The testicular biopsies showed abnormalities mainly in the germinal epithelium. In agreement with previous studies, it was concluded that the abnormalities of sexual development in this syndrome are mainly due to a defect in the hypothalamic pituitary axis. Adrenal function was not found to be grossly abnormal. The 17 ketosteroid excretion values were low, probably explaining the rather sparse pubic and axillary hair observed in these patients. The urinary 17-hydroxycorticosteroid creatinine ratios were found to be elevated, probably due to decreased creatinine excretion, reflecting the muscular abnormalities of these subjects.", "contents": "Hypogonadism in Prader-Willi syndrome. Sexual development was evaluated in 9 female and 2 male subjects with Prader-Willi syndrome. The process of sexual development and degree of genital development attained were found to be variable but abnormal in all subjects. Hypothalamic-pituitary-gonadal functions were evaluated by measurement of serum Luteinizing Hormone and plasma testosterone responses to stimulation by clomiphene citrate and plasma testosterone responses to stimulation by human chorionic gonadotrophin. The degree of vaginal estrogenization was variable. The testicular biopsies showed abnormalities mainly in the germinal epithelium. In agreement with previous studies, it was concluded that the abnormalities of sexual development in this syndrome are mainly due to a defect in the hypothalamic pituitary axis. Adrenal function was not found to be grossly abnormal. The 17 ketosteroid excretion values were low, probably explaining the rather sparse pubic and axillary hair observed in these patients. The urinary 17-hydroxycorticosteroid creatinine ratios were found to be elevated, probably due to decreased creatinine excretion, reflecting the muscular abnormalities of these subjects."} {"id": "PMID:164773", "title": "Partial unilateral cryptophthalmos with syndactyly, brachycephaly, and renal anomalies.", "content": "The cryptophthalmos syndrome consists of cryptophthalmos, dyscephaly, syndactyly, and genitourinary abnormalities. A 2-year-old girl had unilateral partial cryptophthalmos associated with brachycephaly, unilateral syndactyly, and unilateral poor renal visualization.", "contents": "Partial unilateral cryptophthalmos with syndactyly, brachycephaly, and renal anomalies. The cryptophthalmos syndrome consists of cryptophthalmos, dyscephaly, syndactyly, and genitourinary abnormalities. A 2-year-old girl had unilateral partial cryptophthalmos associated with brachycephaly, unilateral syndactyly, and unilateral poor renal visualization."} {"id": "PMID:164775", "title": "A cytoplasmic body in human fetal endothelium.", "content": "We describe a crystalloid-containing inclusion in the cytoplasm of human fetal cells believed to be endothelium. We do not know whether it is peculiar to the fetal period, nor do we know its function.", "contents": "A cytoplasmic body in human fetal endothelium. We describe a crystalloid-containing inclusion in the cytoplasm of human fetal cells believed to be endothelium. We do not know whether it is peculiar to the fetal period, nor do we know its function."} {"id": "PMID:164776", "title": "An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. I. Light microscopic and tissue and organ culture observations.", "content": "The various stages of divergent neuroepithelial differentiation were studied in the solid transplants of a transplantable mouse testicular teratoma (OTT-6050) maintained in both ascitic and solid forms. They included: a) areas of undifferentiated medullary epithelium corresponding to the rare human medulloepithelioma; b) areas of neuroblastic differentiation corresponding to neuroblastoma, with more mature neuronal differentiation corresponding to ganglioneuroma or, when mixed with glial elements, to ganglioglioma; and c) more mature neuroglial areas resembling astrocytoma, oligodendroglioma or ependymoma, as well as more primitive areas corresponding to ependymoblastoma. In tissue culture using collagen-coated coverslips, astrocytic differentiation was found in the outgrowth zone after 15 days, confirmed by immunofluorescence with antibodies to an astroglia-specific protein. In organ culture systems, glial components, including ependymal structures, were preserved in tumor explants, and astrocytic differentiation, as expressed by glial fiber formation, was increased after 4 to 6 weeks in vitro. No neuronal differentiation was demonstrable, however. The neuroepithelial component of this experimental teratoma may provide a model for the study of neoplastic neuroepithelial differentiation.", "contents": "An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. I. Light microscopic and tissue and organ culture observations. The various stages of divergent neuroepithelial differentiation were studied in the solid transplants of a transplantable mouse testicular teratoma (OTT-6050) maintained in both ascitic and solid forms. They included: a) areas of undifferentiated medullary epithelium corresponding to the rare human medulloepithelioma; b) areas of neuroblastic differentiation corresponding to neuroblastoma, with more mature neuronal differentiation corresponding to ganglioneuroma or, when mixed with glial elements, to ganglioglioma; and c) more mature neuroglial areas resembling astrocytoma, oligodendroglioma or ependymoma, as well as more primitive areas corresponding to ependymoblastoma. In tissue culture using collagen-coated coverslips, astrocytic differentiation was found in the outgrowth zone after 15 days, confirmed by immunofluorescence with antibodies to an astroglia-specific protein. In organ culture systems, glial components, including ependymal structures, were preserved in tumor explants, and astrocytic differentiation, as expressed by glial fiber formation, was increased after 4 to 6 weeks in vitro. No neuronal differentiation was demonstrable, however. The neuroepithelial component of this experimental teratoma may provide a model for the study of neoplastic neuroepithelial differentiation."} {"id": "PMID:164778", "title": "Light and electron microscopic studies on human temporal arteries with special reference to alterations related to senescence, atherosclerosis and giant cell arteritis.", "content": "Temporal artery biopsy specimens from 26 patients of various ages with and without giant cell arteritis afforded an opportunity to examine several ultrastructural features of these human muscular arteries, including senescent and atherosclerotic alterations and the fine structural pathology of temporal arteritis. The unusual pathologic features of temporal arteritis were found superimposed on the progressive accumulation of smooth muscle cells, collagen and occasional discrete intimal atherosclerotic plaques in the intima of aging arteries. Two features of giant cell arteritis were conspicuous: first, the accumulation of large numbers of histiocytes and epitheloid and giant cells at the intimal-medial junction and second, fragmentation, degeneration and dissolution of the internal elastic lamina. The close proximity of the granulomatous reaction to the degenerating lamina suggests that these two aspects of the pathologic picture are in some way related, and possible immunologic mechanisms of this relationship are discussed on the basis of the ultrastructural findings.", "contents": "Light and electron microscopic studies on human temporal arteries with special reference to alterations related to senescence, atherosclerosis and giant cell arteritis. Temporal artery biopsy specimens from 26 patients of various ages with and without giant cell arteritis afforded an opportunity to examine several ultrastructural features of these human muscular arteries, including senescent and atherosclerotic alterations and the fine structural pathology of temporal arteritis. The unusual pathologic features of temporal arteritis were found superimposed on the progressive accumulation of smooth muscle cells, collagen and occasional discrete intimal atherosclerotic plaques in the intima of aging arteries. Two features of giant cell arteritis were conspicuous: first, the accumulation of large numbers of histiocytes and epitheloid and giant cells at the intimal-medial junction and second, fragmentation, degeneration and dissolution of the internal elastic lamina. The close proximity of the granulomatous reaction to the degenerating lamina suggests that these two aspects of the pathologic picture are in some way related, and possible immunologic mechanisms of this relationship are discussed on the basis of the ultrastructural findings."} {"id": "PMID:164779", "title": "A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats.", "content": "A chronic renal disease was induced by 5/6 nephrectomy in young adult Wistar albino male rats. Groups of 3 rats were killed at varying time intervals from 10 to 50 weeks after nephrectomy, and the glomerular structure was studied by light and electron microscopy. By light microscopy, increase in glomerular size and hypertrophy of the visceral glomerular epithelial cells were evident as early as the tenth week. Significant degree of glomerular hyalinization started on the 25th week and gradually became more extensive in involvement towards the 50th week. By electron miscroscopy, the hypertrophied glomerular epithelia showed many osmiophilic bodies and vacuoles in their cytoplasm and fusion of foot processes. Beginning on the 30th week, increase of the mesangial matrix was quite evident, and endothelial and epithelial cells disappeared from the areas where the increase was prominent. The increased matrix gradually encroached and occluded capillary lumina and Bowman's space, leading to a formation of obsolescent glomeruli. Whether or not these glomerular changes are due to the glomerular hyperfiltration which has been known to occur after 5/6 nephrectomy remains to be elucidated.", "contents": "A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. A chronic renal disease was induced by 5/6 nephrectomy in young adult Wistar albino male rats. Groups of 3 rats were killed at varying time intervals from 10 to 50 weeks after nephrectomy, and the glomerular structure was studied by light and electron microscopy. By light microscopy, increase in glomerular size and hypertrophy of the visceral glomerular epithelial cells were evident as early as the tenth week. Significant degree of glomerular hyalinization started on the 25th week and gradually became more extensive in involvement towards the 50th week. By electron miscroscopy, the hypertrophied glomerular epithelia showed many osmiophilic bodies and vacuoles in their cytoplasm and fusion of foot processes. Beginning on the 30th week, increase of the mesangial matrix was quite evident, and endothelial and epithelial cells disappeared from the areas where the increase was prominent. The increased matrix gradually encroached and occluded capillary lumina and Bowman's space, leading to a formation of obsolescent glomeruli. Whether or not these glomerular changes are due to the glomerular hyperfiltration which has been known to occur after 5/6 nephrectomy remains to be elucidated."} {"id": "PMID:164786", "title": "Factors affecting long-term survival of patients with bronchogenic carcinoma.", "content": "From January 1963 to December 1968, 148 patients underwent thoracotomy for bronchogenic carcinoma. In 123 patients either lobectomy or pneumonectomy was performed (resectability rate of 84 per cent). The over-all operative mortality was 3.4 per cent. Forty of the patients undergoing resection (34 per cent) are alive and free of cancer five years after surgery. Tumor size, nodal involvement, cell type, location, symptoms, and extent of surgery were studied in relation to the long-term results. Five year survival was directly related to the size of the tumor and the extent of nodal involvement. No patients with mediastinal nodal involvement or with lesions larger than 7 cm in diameter were among the long-term survivors.", "contents": "Factors affecting long-term survival of patients with bronchogenic carcinoma. From January 1963 to December 1968, 148 patients underwent thoracotomy for bronchogenic carcinoma. In 123 patients either lobectomy or pneumonectomy was performed (resectability rate of 84 per cent). The over-all operative mortality was 3.4 per cent. Forty of the patients undergoing resection (34 per cent) are alive and free of cancer five years after surgery. Tumor size, nodal involvement, cell type, location, symptoms, and extent of surgery were studied in relation to the long-term results. Five year survival was directly related to the size of the tumor and the extent of nodal involvement. No patients with mediastinal nodal involvement or with lesions larger than 7 cm in diameter were among the long-term survivors."} {"id": "PMID:164795", "title": "Postanal changes in the localization of glucose 6-phosphatase activity within the liver lobule of the mouse.", "content": "The change in the localization of glucose 6-phosphatase activity within the liver lobule of the mouse was studied during development. From one day before birth to three days after birth, a uniform localization of the activity was observed throughout the lobule. This uniform localization of the acitvity gradually changed to that of the adult type, characterized by a relatively higher activity in periportal areas, between three to ten days of age. This indicates that the postnatal growth of the liver is accompanied by a change in the pattern of the localization of this enzyme activity within the liver lobule. Further, the biochemical results showed that the elevated activity after birth was reduced to the level seen in adult at ten days of age. Thus, the reduction in the level of the enzyme activity during ten days after birth corresponds to a redistribution of the enzyme activity within the liver lobule.", "contents": "Postanal changes in the localization of glucose 6-phosphatase activity within the liver lobule of the mouse. The change in the localization of glucose 6-phosphatase activity within the liver lobule of the mouse was studied during development. From one day before birth to three days after birth, a uniform localization of the activity was observed throughout the lobule. This uniform localization of the acitvity gradually changed to that of the adult type, characterized by a relatively higher activity in periportal areas, between three to ten days of age. This indicates that the postnatal growth of the liver is accompanied by a change in the pattern of the localization of this enzyme activity within the liver lobule. Further, the biochemical results showed that the elevated activity after birth was reduced to the level seen in adult at ten days of age. Thus, the reduction in the level of the enzyme activity during ten days after birth corresponds to a redistribution of the enzyme activity within the liver lobule."} {"id": "PMID:164799", "title": "Immunity to fowlpox.", "content": "Protection against fowlpox develops following vaccination or natural infection. The immune response can be measured for variable times either by challenging immunity of vaccinated birds for protection or by various serologic tests, e.g., viral neutralization, agar gel precipitation, complement fixation, passive hemagglutination, fluorescent antibody, and immunoperoxidase methods. Variation in the antibody response measured by these tests may be due to concentration of antibody present and sensitivity of the test employed. Available information suggests that both humoral and cellular immunity are involved in protection. There is a possibility of persistence of virus in latent infections which also might be responsible for protection.", "contents": "Immunity to fowlpox. Protection against fowlpox develops following vaccination or natural infection. The immune response can be measured for variable times either by challenging immunity of vaccinated birds for protection or by various serologic tests, e.g., viral neutralization, agar gel precipitation, complement fixation, passive hemagglutination, fluorescent antibody, and immunoperoxidase methods. Variation in the antibody response measured by these tests may be due to concentration of antibody present and sensitivity of the test employed. Available information suggests that both humoral and cellular immunity are involved in protection. There is a possibility of persistence of virus in latent infections which also might be responsible for protection."} {"id": "PMID:164800", "title": "Avian viral arthritis: antigenic types and immune response.", "content": "Serums from broiler breeders of an integrated broiler operator were examined for precipitin antibodies using antigens prepared from preliminary reovirus serotypes represented by WVU-2937, Reo-25, Reo-59, and Fahey-Crawley virus. The precipitin antibodies were present in most of the flocks. Virus neutralization tests indicated that the reovirus responsible for viral arthritis represented by WVU-2937 was not present in the breeder flocks, but antibodies to Reo-25, Reo-59, and the Fahey-Crawley viruses were present.", "contents": "Avian viral arthritis: antigenic types and immune response. Serums from broiler breeders of an integrated broiler operator were examined for precipitin antibodies using antigens prepared from preliminary reovirus serotypes represented by WVU-2937, Reo-25, Reo-59, and Fahey-Crawley virus. The precipitin antibodies were present in most of the flocks. Virus neutralization tests indicated that the reovirus responsible for viral arthritis represented by WVU-2937 was not present in the breeder flocks, but antibodies to Reo-25, Reo-59, and the Fahey-Crawley viruses were present."} {"id": "PMID:164801", "title": "Immunity to transmissible (coronaviral) enteritis of turkeys (bluecomb).", "content": "Turkey flocks recovering from natural and laboratory induced coronaviral enteritis developed lifelong immunity. Virus neutralization tests indicated that neutralization capacity of serums from recovered turkeys was low. One-way cross challenge test using turkeys inoculated with various bluecomb isolates revealed close antigenic relationship or antigenic identity among bluecomb isolates. The controlled application of intestinal preparations containing coronavirus as a vaccination procedure had value in developing active lasting immunity but it has limitations in areas that are attempting to eliminate the disease by a depopulation program. Killed vaccines injected parenterally did not produce a detectable immunity.", "contents": "Immunity to transmissible (coronaviral) enteritis of turkeys (bluecomb). Turkey flocks recovering from natural and laboratory induced coronaviral enteritis developed lifelong immunity. Virus neutralization tests indicated that neutralization capacity of serums from recovered turkeys was low. One-way cross challenge test using turkeys inoculated with various bluecomb isolates revealed close antigenic relationship or antigenic identity among bluecomb isolates. The controlled application of intestinal preparations containing coronavirus as a vaccination procedure had value in developing active lasting immunity but it has limitations in areas that are attempting to eliminate the disease by a depopulation program. Killed vaccines injected parenterally did not produce a detectable immunity."} {"id": "PMID:164804", "title": "Ulcerative enteritis--clostridial antigens.", "content": "The causative agent of ulcerative enteritis (UE) is a clostridium and it is believed that it belongs to a new, hitherto undescribed species. It has been named, tentatively, Clostridium colinum. Transmission experiments carried out with artificial cultures of this clostridium have clarified some aspects of the pathogenesis of UE and have brought into focus other aspects of its pathogenesis, epizootiology, and immunology that need to be investigated. Support for research is needed: 1) To investigate the distribution in nature of C colinum. For this purpose the development of more suitable selective and differential culture mediums should be encouraged. 2) To further study the pathogenesis of UE through application of the fluorescent labeled antibody procedure. 3) To search for toxins produced by this clostridium, possibly through use of ligated intestinal loops in chickens. 4) To develop a quick and simple means for the differential diagnosis of UE. Use of a fluorescent antibody test has been suggested as an area of research to fill this need.", "contents": "Ulcerative enteritis--clostridial antigens. The causative agent of ulcerative enteritis (UE) is a clostridium and it is believed that it belongs to a new, hitherto undescribed species. It has been named, tentatively, Clostridium colinum. Transmission experiments carried out with artificial cultures of this clostridium have clarified some aspects of the pathogenesis of UE and have brought into focus other aspects of its pathogenesis, epizootiology, and immunology that need to be investigated. Support for research is needed: 1) To investigate the distribution in nature of C colinum. For this purpose the development of more suitable selective and differential culture mediums should be encouraged. 2) To further study the pathogenesis of UE through application of the fluorescent labeled antibody procedure. 3) To search for toxins produced by this clostridium, possibly through use of ligated intestinal loops in chickens. 4) To develop a quick and simple means for the differential diagnosis of UE. Use of a fluorescent antibody test has been suggested as an area of research to fill this need."} {"id": "PMID:164807", "title": "Experimentally induced respiratory syncytial viral infection in calves.", "content": "Calves exposed by intranasal (IN) or intratracheal (IT) or both routes of inoculation to bovine respiratory syncytial (BRS) virus had a transient increase in body temperature for 2 days. Histopathologic changes indicative of pneumonia, along with multinucleated giant cells, were observed in alveolar lumen. The virus was recovered from infected calves, and their serologic response was poor. In a limited serologic survey with 100 serums from cattle in Maryland, low levels of serum-neutralizing (SN) antibody to the virus were prevalent in 38% of the serums.", "contents": "Experimentally induced respiratory syncytial viral infection in calves. Calves exposed by intranasal (IN) or intratracheal (IT) or both routes of inoculation to bovine respiratory syncytial (BRS) virus had a transient increase in body temperature for 2 days. Histopathologic changes indicative of pneumonia, along with multinucleated giant cells, were observed in alveolar lumen. The virus was recovered from infected calves, and their serologic response was poor. In a limited serologic survey with 100 serums from cattle in Maryland, low levels of serum-neutralizing (SN) antibody to the virus were prevalent in 38% of the serums."} {"id": "PMID:164808", "title": "Immunity and the level of neutralization antibodies in foals and mares vaccinated with a modified live-virus rhinopneumonitis vaccine.", "content": "Foals (farms 1 and 2) and mares (farms 1 and 3) vaccinated with a commercially available rhinopneumonitis vaccine were tested for the level of antibodies and for protection against the natural infection. The serum-neutralization (SN) antibody titers against equine herpesvirus type 1 were 1:8 or less in the majority of foals and 1:16 or higher in about 10%. The level of the nasal secretory antibody in the foals (farm 2) was less than 1:4. The vaccinated foals did not show any apparent respiratory tract infection for about 6 months and then an epizootic of respiratory tract disease appeared on farm 1 involving 3 foals. From each of these 3 foals herpesvirus was isolated. On farm 1, about 50% of the vaccinated mares aborted, and on farm 3, there were no abortions. Isolations of herpesvirus were made from 5 of the 6 aborted fetuses (farm 1). The SN antibody titers of the pregnant mares in the 2 farms at the time of foaling were high.", "contents": "Immunity and the level of neutralization antibodies in foals and mares vaccinated with a modified live-virus rhinopneumonitis vaccine. Foals (farms 1 and 2) and mares (farms 1 and 3) vaccinated with a commercially available rhinopneumonitis vaccine were tested for the level of antibodies and for protection against the natural infection. The serum-neutralization (SN) antibody titers against equine herpesvirus type 1 were 1:8 or less in the majority of foals and 1:16 or higher in about 10%. The level of the nasal secretory antibody in the foals (farm 2) was less than 1:4. The vaccinated foals did not show any apparent respiratory tract infection for about 6 months and then an epizootic of respiratory tract disease appeared on farm 1 involving 3 foals. From each of these 3 foals herpesvirus was isolated. On farm 1, about 50% of the vaccinated mares aborted, and on farm 3, there were no abortions. Isolations of herpesvirus were made from 5 of the 6 aborted fetuses (farm 1). The SN antibody titers of the pregnant mares in the 2 farms at the time of foaling were high."} {"id": "PMID:164809", "title": "Colon and rectal cancer in the young adult.", "content": "801 patients with colon and rectal cancer were studied to assess the behavior of this cancer in the patient under 40 years of age as contrasted to the more commonly seen older patient. The younger patient had a greater frequency of advanced signs, later stages of cancer and mucoid carcinoma. However, when compared by clinical staging, the younger patient did as well or better than his older counterpart. Clinical staging was the most important prognostic factor irrespective of age. No inherent difference was found in the virulence of the cancer in the young, as the five-year survival in the younger patient (31 percent) was essentially the same as in the older patient (32 percent).", "contents": "Colon and rectal cancer in the young adult. 801 patients with colon and rectal cancer were studied to assess the behavior of this cancer in the patient under 40 years of age as contrasted to the more commonly seen older patient. The younger patient had a greater frequency of advanced signs, later stages of cancer and mucoid carcinoma. However, when compared by clinical staging, the younger patient did as well or better than his older counterpart. Clinical staging was the most important prognostic factor irrespective of age. No inherent difference was found in the virulence of the cancer in the young, as the five-year survival in the younger patient (31 percent) was essentially the same as in the older patient (32 percent)."} {"id": "PMID:164810", "title": "Pathophysiology of acupuncture: nervous system transmission.", "content": "As far as we know, this is the first scientific report which shows distinctly that acupuncture is transmitted directly by the nervous system and the performance of analgesic acupuncture requires an intact nervous system. The more distal the acupuncture treatment is given upon the nerve, the greater the degree of analgesia is afforded. The slowing from a normal awake beta to a normal awake alpha electroencephalographic rhythm may have some effect on the patient's pain perception but further investigation is required.", "contents": "Pathophysiology of acupuncture: nervous system transmission. As far as we know, this is the first scientific report which shows distinctly that acupuncture is transmitted directly by the nervous system and the performance of analgesic acupuncture requires an intact nervous system. The more distal the acupuncture treatment is given upon the nerve, the greater the degree of analgesia is afforded. The slowing from a normal awake beta to a normal awake alpha electroencephalographic rhythm may have some effect on the patient's pain perception but further investigation is required."} {"id": "PMID:164811", "title": "Surgical intervention in intestinal amebiasis.", "content": "Operative intervention in patients with unrecognized and untreated amebomas or acute fulminating amebic colitis may result in severe complications. Nevertheless, certain clinical presentations of intestinal amebiasis require surgical procedures varying from drainage of an abscess to a subtotal colectomy. If, in patients with acute fulminating amebic colitis, the signs or symptoms of intraperitoneal or impending perforation develop, unremitting diarrhea associated with anemia and hypoproteinemia continues, or localized abscsses fail to improve with chemotherapy, operative intervention is indicated. Complications of amebomas that require operative intervention include failure to respond to chemotherapy, perforation, hemorrhage, ulceration, stricture or fistula formation and obstruction. Anti-amebic chemotherapy can reduce intestinal complications so elective operative procedures should be delayed to allow time for adequate treatment.", "contents": "Surgical intervention in intestinal amebiasis. Operative intervention in patients with unrecognized and untreated amebomas or acute fulminating amebic colitis may result in severe complications. Nevertheless, certain clinical presentations of intestinal amebiasis require surgical procedures varying from drainage of an abscess to a subtotal colectomy. If, in patients with acute fulminating amebic colitis, the signs or symptoms of intraperitoneal or impending perforation develop, unremitting diarrhea associated with anemia and hypoproteinemia continues, or localized abscsses fail to improve with chemotherapy, operative intervention is indicated. Complications of amebomas that require operative intervention include failure to respond to chemotherapy, perforation, hemorrhage, ulceration, stricture or fistula formation and obstruction. Anti-amebic chemotherapy can reduce intestinal complications so elective operative procedures should be delayed to allow time for adequate treatment."} {"id": "PMID:164812", "title": "[Hypoglycemic convulsions and hypopituitarism].", "content": "A case of hypopituitarism in a female, aged 6 months, whose first symptom consisted of hypoglycemic convulsions is reported. Making use of TRH we confirm the hypothalamic origin of pituitary failure. Substitution therapy controlled the episodes of convulsions and normalized the growth rate of the child.", "contents": "[Hypoglycemic convulsions and hypopituitarism]. A case of hypopituitarism in a female, aged 6 months, whose first symptom consisted of hypoglycemic convulsions is reported. Making use of TRH we confirm the hypothalamic origin of pituitary failure. Substitution therapy controlled the episodes of convulsions and normalized the growth rate of the child."} {"id": "PMID:164814", "title": "Collagenase activity in epidermoid carcinoma of the oral cavity and larynx.", "content": "Summary--Tumor invasion requires the breadkdown of the main structural protein, collagen. A series of fourteen epidermoid carcinomas of the larynx and oral cavity produced a collagen dissolving enzyme in vitro as demonstrated by the breakdown of 14C-labeled collagen. Oral cavity tumors showed greater activity than laryngeal carcinomas while both sites were more active than uninvolved mucosa from the same patients. Tumor associated collagenase activity, in common with previously described collagenases, can only be demonstrated in vitro and requires protein synthesis. Maximum tumor collagenase occurred at 24 hours in vitro and then declined as compared with the maximum collagenase at 72 hours in vitro produced by oral cavity mucosa. The 14 patients in our series were ranked in order of the collagenase activity of their tumors. At 18 months after the diagnosis, four of the six patients with the most active tumors were dead of cancer and one patient was alive with persistent cancer. High collagenase activity may be a factor in the clinical aggressiveness of epidermoid carcinomas of the head and neck.", "contents": "Collagenase activity in epidermoid carcinoma of the oral cavity and larynx. Summary--Tumor invasion requires the breadkdown of the main structural protein, collagen. A series of fourteen epidermoid carcinomas of the larynx and oral cavity produced a collagen dissolving enzyme in vitro as demonstrated by the breakdown of 14C-labeled collagen. Oral cavity tumors showed greater activity than laryngeal carcinomas while both sites were more active than uninvolved mucosa from the same patients. Tumor associated collagenase activity, in common with previously described collagenases, can only be demonstrated in vitro and requires protein synthesis. Maximum tumor collagenase occurred at 24 hours in vitro and then declined as compared with the maximum collagenase at 72 hours in vitro produced by oral cavity mucosa. The 14 patients in our series were ranked in order of the collagenase activity of their tumors. At 18 months after the diagnosis, four of the six patients with the most active tumors were dead of cancer and one patient was alive with persistent cancer. High collagenase activity may be a factor in the clinical aggressiveness of epidermoid carcinomas of the head and neck."} {"id": "PMID:164815", "title": "Primary oat-cell carcinoma of head and neck.", "content": "Summary--A case of primary oat-cell carcinoma of the larynx in a 68-year-old white female is described, bringing to a total of three the reported cases in the world literature. The tumor is highly malignant and notorious for the speed with which it metastasizes. Treatment should be aggressive from the beginning. We believe that even for a localized tumor of this kind, a minimal procedure should be widefield laryngectomy with elective radical neck dissection even if clinically, nodes are not palpable. Since the tumor is highly radiosensitive, radiotherapy should be used postoperatively.", "contents": "Primary oat-cell carcinoma of head and neck. Summary--A case of primary oat-cell carcinoma of the larynx in a 68-year-old white female is described, bringing to a total of three the reported cases in the world literature. The tumor is highly malignant and notorious for the speed with which it metastasizes. Treatment should be aggressive from the beginning. We believe that even for a localized tumor of this kind, a minimal procedure should be widefield laryngectomy with elective radical neck dissection even if clinically, nodes are not palpable. Since the tumor is highly radiosensitive, radiotherapy should be used postoperatively."} {"id": "PMID:164816", "title": "The biochemistry of collagen.", "content": "Collagen synthesis and subsequent extracellular stabilization and turnover are multi-step processes. The sequence of events in these processes is reviewed and correlated with collagen pathologies.", "contents": "The biochemistry of collagen. Collagen synthesis and subsequent extracellular stabilization and turnover are multi-step processes. The sequence of events in these processes is reviewed and correlated with collagen pathologies."} {"id": "PMID:164820", "title": "[Experimental effect of bruneomycin on the energy metabolism of liver tissue].", "content": "The effect of an antitumor antibiotic bruneomycin on the energy metabolism in the liver tissue was studied. Four hours after the drug administration the consumption of glycogen and glucose in the liver tissue increased because of glycogenolysis activation, which was evident from increased activity of prosphorylase, phosphofructokinase, hexokinase and summation glycolytic activity. 24 and 48 hours after the antibiotic administration the balance of consumption and resynthesis of phosphate macroergs in the liver tissue impaired, which was evident from decreased levels of ATP, impairement of conjugation of the processes of oxidation due to impairement of permeability and structural integrity of the mitochondrial membranes. Further decrease in the glycogen liver levels was mainly due to suppressed resynthesis of glycogen because of destructive-necrotic processes. Simultaneously the processes of glycolytic splitting of glucose decreased which was evident from decreased activity of the enzymes and summation glycolytic activity.", "contents": "[Experimental effect of bruneomycin on the energy metabolism of liver tissue]. The effect of an antitumor antibiotic bruneomycin on the energy metabolism in the liver tissue was studied. Four hours after the drug administration the consumption of glycogen and glucose in the liver tissue increased because of glycogenolysis activation, which was evident from increased activity of prosphorylase, phosphofructokinase, hexokinase and summation glycolytic activity. 24 and 48 hours after the antibiotic administration the balance of consumption and resynthesis of phosphate macroergs in the liver tissue impaired, which was evident from decreased levels of ATP, impairement of conjugation of the processes of oxidation due to impairement of permeability and structural integrity of the mitochondrial membranes. Further decrease in the glycogen liver levels was mainly due to suppressed resynthesis of glycogen because of destructive-necrotic processes. Simultaneously the processes of glycolytic splitting of glucose decreased which was evident from decreased activity of the enzymes and summation glycolytic activity."} {"id": "PMID:164817", "title": "Erythropoietin production in renal tumors.", "content": "A review of the pertinent literature on the relation of erythropoietin production to the presence of renal neoplasm suggests that erythropoietin may be produced either directly by the tumor or indirectly by its physical effect on the adjoining normal renal tissue. The most commonly found tumors which are associated with elevated levels of serum and urinary erythropoietin are the hypernephromas. However, the presence of erythropoietin and an associated erythrocytosis even here occurs only relatively infrequently. Some studies have demonstrated the presence of erythropoietin activity in tumor tissue itself but erythropoietin has not been isolated from renal tumor tissue. In some patients with Wilms' tumor, erythropoietin blood levels may also be increased; however, erythrocytosis in these patients is not a characteristic feature. Other renal tumors rarely produce erythrocytosis and presumably no erythropoietin. Possible explanations for the production of erythropoietin by renal tumors are discussed.", "contents": "Erythropoietin production in renal tumors. A review of the pertinent literature on the relation of erythropoietin production to the presence of renal neoplasm suggests that erythropoietin may be produced either directly by the tumor or indirectly by its physical effect on the adjoining normal renal tissue. The most commonly found tumors which are associated with elevated levels of serum and urinary erythropoietin are the hypernephromas. However, the presence of erythropoietin and an associated erythrocytosis even here occurs only relatively infrequently. Some studies have demonstrated the presence of erythropoietin activity in tumor tissue itself but erythropoietin has not been isolated from renal tumor tissue. In some patients with Wilms' tumor, erythropoietin blood levels may also be increased; however, erythrocytosis in these patients is not a characteristic feature. Other renal tumors rarely produce erythrocytosis and presumably no erythropoietin. Possible explanations for the production of erythropoietin by renal tumors are discussed."} {"id": "PMID:164821", "title": "Interpretation of the tube coagulase test for identification of Staphylococcus aureus.", "content": "The tube coagulase test is a valid means of identifying Staphylococcus auerus, provided that only a firm clot that does not move when the tube is tipped is considered a positive reaction. The widely promulgated interpretation that all degrees of clotting in coagulase plasma are a positive identification of S. auerus was disproved by the use of other tests such as anaerobic glucose fermentation, thermonuclease production, and lysostaphin sensitivity. It was found that the source of supply of the coagulase plasma is a factor in the occurrence of false-positive coagulase test results. The use of a mixture of pig and rabbit plasma in the tube coagulase test is also discussed.", "contents": "Interpretation of the tube coagulase test for identification of Staphylococcus aureus. The tube coagulase test is a valid means of identifying Staphylococcus auerus, provided that only a firm clot that does not move when the tube is tipped is considered a positive reaction. The widely promulgated interpretation that all degrees of clotting in coagulase plasma are a positive identification of S. auerus was disproved by the use of other tests such as anaerobic glucose fermentation, thermonuclease production, and lysostaphin sensitivity. It was found that the source of supply of the coagulase plasma is a factor in the occurrence of false-positive coagulase test results. The use of a mixture of pig and rabbit plasma in the tube coagulase test is also discussed."} {"id": "PMID:164822", "title": "Production of hydrogen cyanide by Pseudomonas fluorescens.", "content": "Two Pseudomonas fluorescens isolates were found to produce hydrogen cyanide when cultured on either Trypticase soy agar supplemented with 0.5% yeast extract or on irradiation-sterilized chicken.", "contents": "Production of hydrogen cyanide by Pseudomonas fluorescens. Two Pseudomonas fluorescens isolates were found to produce hydrogen cyanide when cultured on either Trypticase soy agar supplemented with 0.5% yeast extract or on irradiation-sterilized chicken."} {"id": "PMID:164838", "title": "Prediction of adult height from height, bone age, and occurrence of menarche, at ages 4 to 16 with allowance for midparent height.", "content": "Multiple regression equations for predicting the adult height of boys and girls from height and bone age at ages 4 and upwards are presented. There is a separate equation for each half year of chronological age; and for pre- and postmenarcheal girls at ages 11 to 14. These are based on longitudinal data from 116 boys and 95 girls of the Harpenden Growth Study and the London group of the International Children's Centre longitudinal study. The bone age used is the revised version of the Tanner-Whitehouse standards, omitting the score for carpal bones (RUS age, TW 2 system). Boys aged 4 to 12 are predicted in 95% of instances to within plus or minus 7 cm of true height, and at ages 13 and 14 to within plus or minus 6 cm. Girls ages 4 to 11 are predicted to within plus or minus 6 cm; premenarcheal girls aged 12 and 13 to within plus or minus 5 and plus or minus 4 cm, respectively; and postmenarcheal girls aged 12 and 13 to within plus or minus 4 and plus or minus 3 cm, respectively. Prediction can be somewhat imporved by allowing for midparent height. One-third of the amount that midparent height differs from mean midparent height is added or subtracted. An alternative system of equations which are based on initial classification by bone age rather than chronological age is given. These have about the same accuracy as the equations based on initial classification by chronological age, but allowance for bone age retardation is less. It is not clear which system is preferable. The equations probably apply to girls complaining of tall stature and boys or girls complaining of shortness and needing reassurance as to normality. In clearly pathological children, such as those with endocrinopathies, they do not apply.", "contents": "Prediction of adult height from height, bone age, and occurrence of menarche, at ages 4 to 16 with allowance for midparent height. Multiple regression equations for predicting the adult height of boys and girls from height and bone age at ages 4 and upwards are presented. There is a separate equation for each half year of chronological age; and for pre- and postmenarcheal girls at ages 11 to 14. These are based on longitudinal data from 116 boys and 95 girls of the Harpenden Growth Study and the London group of the International Children's Centre longitudinal study. The bone age used is the revised version of the Tanner-Whitehouse standards, omitting the score for carpal bones (RUS age, TW 2 system). Boys aged 4 to 12 are predicted in 95% of instances to within plus or minus 7 cm of true height, and at ages 13 and 14 to within plus or minus 6 cm. Girls ages 4 to 11 are predicted to within plus or minus 6 cm; premenarcheal girls aged 12 and 13 to within plus or minus 5 and plus or minus 4 cm, respectively; and postmenarcheal girls aged 12 and 13 to within plus or minus 4 and plus or minus 3 cm, respectively. Prediction can be somewhat imporved by allowing for midparent height. One-third of the amount that midparent height differs from mean midparent height is added or subtracted. An alternative system of equations which are based on initial classification by bone age rather than chronological age is given. These have about the same accuracy as the equations based on initial classification by chronological age, but allowance for bone age retardation is less. It is not clear which system is preferable. The equations probably apply to girls complaining of tall stature and boys or girls complaining of shortness and needing reassurance as to normality. In clearly pathological children, such as those with endocrinopathies, they do not apply."} {"id": "PMID:164841", "title": "Seminoma of the anterior mediastinum.", "content": "Primary pure cell seminoma of the mediastinum is a rare and potentially fatal lesion. Encroachment on or invasion of adjacent structures is common, as are distant metastases. The differentiation between pure cell seminomas and mixed germ cell tumors should be made since the extreme radiosensitivity of seminomas improves the prognosis. The presence of metastases from primary mediastinal seminomas, as with testicular germinomas, need not be a deterrent to long-term cure. Recommended therapy consists of total or subtotal removal, radiation therapy (2,500 to 3,500 rads delivered over 2 to 4 weeks), and, in some patients, chemotherapy. A patient who was successfully treated with subtotal removal and irradiation is presented.", "contents": "Seminoma of the anterior mediastinum. Primary pure cell seminoma of the mediastinum is a rare and potentially fatal lesion. Encroachment on or invasion of adjacent structures is common, as are distant metastases. The differentiation between pure cell seminomas and mixed germ cell tumors should be made since the extreme radiosensitivity of seminomas improves the prognosis. The presence of metastases from primary mediastinal seminomas, as with testicular germinomas, need not be a deterrent to long-term cure. Recommended therapy consists of total or subtotal removal, radiation therapy (2,500 to 3,500 rads delivered over 2 to 4 weeks), and, in some patients, chemotherapy. A patient who was successfully treated with subtotal removal and irradiation is presented."} {"id": "PMID:164842", "title": "Bronchial adenoma.", "content": "Thirty-three patients with bronchial adenoma have been treated in U.S. Army hospitals. These included 27 with carcinoid, 3 with mucoepidermoid carcinoma, and 3 with adenoid cystic carcinoma. No deaths could be directly related to the adenomas during an average follow-up of 14.5 years.", "contents": "Bronchial adenoma. Thirty-three patients with bronchial adenoma have been treated in U.S. Army hospitals. These included 27 with carcinoid, 3 with mucoepidermoid carcinoma, and 3 with adenoid cystic carcinoma. No deaths could be directly related to the adenomas during an average follow-up of 14.5 years."} {"id": "PMID:164844", "title": "Excitation-contraction uncoupling. The effect of hyperosomolar glycerol solution and antrolene sodium on mammalian muscle in vitro.", "content": "In the rat hemidiaphragm, in vitro dantrolene sodium irreversibly reduced twitch tension up to 20% of the original value in 20 minutes of exposure. The phenomenon was dose related. Dantrolene sodium did not affect (1) resting membrane potential (IMP); (2) miniature endplate potential frequency of amplitude; or (3) endplate potential amplitude decrement of repetitively stimulated partially curarized muscle. A combination of hyperosmolar solutions of glycerol and dantrolene sodium abolished contraction of mammalian muscle with no demonstrable effect on neuromuscular transmission or muscle fiber RMP. With this technique, prolonged recording from repetitively activated muscle fibers is possible.", "contents": "Excitation-contraction uncoupling. The effect of hyperosomolar glycerol solution and antrolene sodium on mammalian muscle in vitro. In the rat hemidiaphragm, in vitro dantrolene sodium irreversibly reduced twitch tension up to 20% of the original value in 20 minutes of exposure. The phenomenon was dose related. Dantrolene sodium did not affect (1) resting membrane potential (IMP); (2) miniature endplate potential frequency of amplitude; or (3) endplate potential amplitude decrement of repetitively stimulated partially curarized muscle. A combination of hyperosmolar solutions of glycerol and dantrolene sodium abolished contraction of mammalian muscle with no demonstrable effect on neuromuscular transmission or muscle fiber RMP. With this technique, prolonged recording from repetitively activated muscle fibers is possible."} {"id": "PMID:164845", "title": "Histochemistry of trauma after electrode implantation and stimulation in the hippocampus.", "content": "Electrodes were implanted into the rat hippocampus in both hemispheres for increasing periods of up to 60 days, and the effects of trauma and electrical stimulation of enzymes controlling cell metabolism in the region of implantation were examined and assessed in relation to studies on humans. In the unstimulated hippocampus as a control, enzyme changes were mainly confined to a narrow area of tissue damage surrounding the electrode. The enzyme changes in response to trauma varied widely; some enzymes controlling tissue respiration showed early and rapid changes, increasing in hyperactive, swollen glial cells and vascular endothelium and decreasing in nerve cells and neuropile. Acid phosphatase activity also increased rapidly in glial cells; other phosphate-releasing enzymes increased more gradually with time. A turning point in these chages was apparent between 25 and 40 days, followed by a reversion to more normal levels at 60 days. Electrical stimulation of the hippocampus in the contralateral hemisphere produced no detectable enzyme changes from those of the unstimulated hippocampus.", "contents": "Histochemistry of trauma after electrode implantation and stimulation in the hippocampus. Electrodes were implanted into the rat hippocampus in both hemispheres for increasing periods of up to 60 days, and the effects of trauma and electrical stimulation of enzymes controlling cell metabolism in the region of implantation were examined and assessed in relation to studies on humans. In the unstimulated hippocampus as a control, enzyme changes were mainly confined to a narrow area of tissue damage surrounding the electrode. The enzyme changes in response to trauma varied widely; some enzymes controlling tissue respiration showed early and rapid changes, increasing in hyperactive, swollen glial cells and vascular endothelium and decreasing in nerve cells and neuropile. Acid phosphatase activity also increased rapidly in glial cells; other phosphate-releasing enzymes increased more gradually with time. A turning point in these chages was apparent between 25 and 40 days, followed by a reversion to more normal levels at 60 days. Electrical stimulation of the hippocampus in the contralateral hemisphere produced no detectable enzyme changes from those of the unstimulated hippocampus."} {"id": "PMID:164846", "title": "Toxic polyneuropathy due to methyl n-butyl ketone. An industrial outbreak.", "content": "Cases of toxic distal polyneuropathy have been studied in a plant producing plastic-coated and color-printed fabrics. After the screenig of 1,157 employees, a total of 86 verified cases were detected. Of these, 11 were moderate to severe in intensity and usually with motor and sensory involvement; 38 were mild, with sensory signs prevailing; and 37 were minimal, but with characteristic electro-diagnostic abnormalities. Muscle weakness and electromyographic abnormalities were predominantly distal. Reflex loss was minimal. Sensory deficits were distal and limited to pain, touch, and temperature discrimination with occasional loss of vibration sense. The distribution of involvement severity of the disorder, and temporal course of the outbreak correlated with exposure with methyl n-butyl ketone. After elimination of this agent improvement was noted in the majority of cases.", "contents": "Toxic polyneuropathy due to methyl n-butyl ketone. An industrial outbreak. Cases of toxic distal polyneuropathy have been studied in a plant producing plastic-coated and color-printed fabrics. After the screenig of 1,157 employees, a total of 86 verified cases were detected. Of these, 11 were moderate to severe in intensity and usually with motor and sensory involvement; 38 were mild, with sensory signs prevailing; and 37 were minimal, but with characteristic electro-diagnostic abnormalities. Muscle weakness and electromyographic abnormalities were predominantly distal. Reflex loss was minimal. Sensory deficits were distal and limited to pain, touch, and temperature discrimination with occasional loss of vibration sense. The distribution of involvement severity of the disorder, and temporal course of the outbreak correlated with exposure with methyl n-butyl ketone. After elimination of this agent improvement was noted in the majority of cases."} {"id": "PMID:164847", "title": "Mechanism of colistin-induced neuromuscular depression.", "content": "The effect of a high concentration of the antibiotic colistin sulfate on neuromuscular transmission was examined by recording intracellularly from rat diaphragm blocked with tubocurarine chloride. The presynaptic effect of colistin was different from that of neomycin sulfate, which reduces the probability of acetylcholine release: Colistin reduced that the quantum content of the initial and the last 20 end-plate potentials of a train of 40 stimuli without altering the probability of acetylcholine release. The quantum size was reduced, while the frequency of miniature end-plate potentials was unchanged.", "contents": "Mechanism of colistin-induced neuromuscular depression. The effect of a high concentration of the antibiotic colistin sulfate on neuromuscular transmission was examined by recording intracellularly from rat diaphragm blocked with tubocurarine chloride. The presynaptic effect of colistin was different from that of neomycin sulfate, which reduces the probability of acetylcholine release: Colistin reduced that the quantum content of the initial and the last 20 end-plate potentials of a train of 40 stimuli without altering the probability of acetylcholine release. The quantum size was reduced, while the frequency of miniature end-plate potentials was unchanged."} {"id": "PMID:164848", "title": "Adrenoleukodystrophy. Electron microscopic findings.", "content": "Ultrastructural and neurochemical studies were done on three male patients with adrenoleukodystrophy. In each case, the affected white matter contained enlarged glial cells filled with pathognomic intracytoplasmic inclusions consisting of electron-lucent spicules bounded by 25-Angstrom wide membranes. Similar inclusions were present in adrenocortical cells. These findings and a review of 47 reported cases indicate that adrenoleukodystrophy is a storage disorder caused by a sex-linked recessive error of metabolism.", "contents": "Adrenoleukodystrophy. Electron microscopic findings. Ultrastructural and neurochemical studies were done on three male patients with adrenoleukodystrophy. In each case, the affected white matter contained enlarged glial cells filled with pathognomic intracytoplasmic inclusions consisting of electron-lucent spicules bounded by 25-Angstrom wide membranes. Similar inclusions were present in adrenocortical cells. These findings and a review of 47 reported cases indicate that adrenoleukodystrophy is a storage disorder caused by a sex-linked recessive error of metabolism."} {"id": "PMID:164849", "title": "Methysergide in the treatment of narcolepsy.", "content": "Five patients with narcolepsy (four with the allied symptom of cataplexy) were treated with the serotonin antagonist methysergide. All patients had as good control of their sleep attacks while on methysergide therapy as on a control period of dextroamphetamine therapy. The cataplexy was less well controlled by methysergide than by dextroamphetamine, but improved when compared to a period without medication. Two patients developed severe calf claudication while on methysergide.", "contents": "Methysergide in the treatment of narcolepsy. Five patients with narcolepsy (four with the allied symptom of cataplexy) were treated with the serotonin antagonist methysergide. All patients had as good control of their sleep attacks while on methysergide therapy as on a control period of dextroamphetamine therapy. The cataplexy was less well controlled by methysergide than by dextroamphetamine, but improved when compared to a period without medication. Two patients developed severe calf claudication while on methysergide."} {"id": "PMID:164877", "title": "[Antigenic characteristics of hamster cells transformed by polyoma virus].", "content": "A hamster cell line derived from a polyoma virus induced tumour (G-Py) was found positive for TSTA and S antigen detected by the surface immunofluorescence technique. Lung metastases were observed in some hamster able to reject a G-Py cell challenge dose injected by intradermal route.", "contents": "[Antigenic characteristics of hamster cells transformed by polyoma virus]. A hamster cell line derived from a polyoma virus induced tumour (G-Py) was found positive for TSTA and S antigen detected by the surface immunofluorescence technique. Lung metastases were observed in some hamster able to reject a G-Py cell challenge dose injected by intradermal route."} {"id": "PMID:164878", "title": "[Double clone in cells of pleural effusion caused by metastasis of oat cell carcinoma of the lung].", "content": "The Authors report a chromosome study carried out on pleural effusion cells from metastases of oat cell carcinoma. They observed a double cell clone: the former, with 44 chromosomes, with various alterations of the karyotype and a big acrocentric \"marker\", the latter, with 45 chromosomes with various alterations of the karyotype and a big submetacentric \"marker\". From these observations the Authors draw some interpretative considerations.", "contents": "[Double clone in cells of pleural effusion caused by metastasis of oat cell carcinoma of the lung]. The Authors report a chromosome study carried out on pleural effusion cells from metastases of oat cell carcinoma. They observed a double cell clone: the former, with 44 chromosomes, with various alterations of the karyotype and a big acrocentric \"marker\", the latter, with 45 chromosomes with various alterations of the karyotype and a big submetacentric \"marker\". From these observations the Authors draw some interpretative considerations."} {"id": "PMID:164879", "title": "Neurotoxicity of acrylamide and its analogues and effects of these analogues and other agents on acrylamide neuropathy.", "content": "N-Hydroxymethylacrylamide, N-methylacrylamide, and N,N-diethylacrylamide produce peripheral neuropathy in rats. Seven other compounds related to acrylamide do not produce neuropathy. Rats given one of the three neurotoxic compounds are more susceptible to acrylamide. A regime for testing acrylamide analogues for neuro-toxicity is suggested. DDT, phenobarbitone, or high dietary concentrations of vitamin A or E have no effect on the development of acrylamide neuropathy in rats. Acrylamide produces neuropathy in hens but not in frogs or goldfish.", "contents": "Neurotoxicity of acrylamide and its analogues and effects of these analogues and other agents on acrylamide neuropathy. N-Hydroxymethylacrylamide, N-methylacrylamide, and N,N-diethylacrylamide produce peripheral neuropathy in rats. Seven other compounds related to acrylamide do not produce neuropathy. Rats given one of the three neurotoxic compounds are more susceptible to acrylamide. A regime for testing acrylamide analogues for neuro-toxicity is suggested. DDT, phenobarbitone, or high dietary concentrations of vitamin A or E have no effect on the development of acrylamide neuropathy in rats. Acrylamide produces neuropathy in hens but not in frogs or goldfish."} {"id": "PMID:164880", "title": "A cohort study of bronchial carcinomas in workers producing chromate pigments.", "content": "A cohort study of the incidence of bronchial cancer in male workers in a small company producing chromate pigments is presented. Altogether 133 workers had been employed by the company from the time production was started in 1948 until the end of 1972. Workers with more than three years employment were included in the study, and three cases of bronchial carcinoma were found among the 24 workers who fulfilled this requirement. Based on the data of the Cancer Registry of Norway the risk of bronchial cancer for a corresponding group of the general population was found to be 0.079, which gives a risk ratio for exposed workers of approximately 38. The average age of the cancer patients was as low as 50 years at the time of diagnosis. All workers in the company had been exposed mainly to zinc chromate dust, and the exposure levels of the workers developing bronchial cancers had probably been from 0-5 to 1-5 mg Cr/m-3 for six to nine years. Two of the three patients were smokers. It is assumed that exposure to chromate pigments, and probably to zinc chromate, may be related to the increased incidence of bronchial cancer in this group of workers. The possibility of a contributing effect of tobacco smoking in at least two of the three cases cannot be ruled out.", "contents": "A cohort study of bronchial carcinomas in workers producing chromate pigments. A cohort study of the incidence of bronchial cancer in male workers in a small company producing chromate pigments is presented. Altogether 133 workers had been employed by the company from the time production was started in 1948 until the end of 1972. Workers with more than three years employment were included in the study, and three cases of bronchial carcinoma were found among the 24 workers who fulfilled this requirement. Based on the data of the Cancer Registry of Norway the risk of bronchial cancer for a corresponding group of the general population was found to be 0.079, which gives a risk ratio for exposed workers of approximately 38. The average age of the cancer patients was as low as 50 years at the time of diagnosis. All workers in the company had been exposed mainly to zinc chromate dust, and the exposure levels of the workers developing bronchial cancers had probably been from 0-5 to 1-5 mg Cr/m-3 for six to nine years. Two of the three patients were smokers. It is assumed that exposure to chromate pigments, and probably to zinc chromate, may be related to the increased incidence of bronchial cancer in this group of workers. The possibility of a contributing effect of tobacco smoking in at least two of the three cases cannot be ruled out."} {"id": "PMID:164881", "title": "Long-term effects on the health of men engaged in the manufacture of tolylene di-isocyanate.", "content": "A prospective study of workers engaged in the manufacture of tolylene di-isocyanate (TDI) was carried out over nine years. The study was in two parts: (1) assessment of the symptoms and ventilatory function of men working on the plants who did not complain of respiratory symptoms; (2) assessment of the long-term effects in men who were removed from the plants because of respiratory symptoms. Use of the MRC Questionnaire on Respiratory Symptoms in a group of 76 TDI workers showed no significant differences in symptoms compared with 76 control subjects. Annual lung function tests were carried out on 180 asymptomatic men with possible exposure to TDI. The relationship of the forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) to the height, age, and duration of exposure was examined by linear regression analysis. The equations formulated did not differ significantly from those calculated for non-TDI exposed subjects. Thus exposure to very small concentrations of TDI does not necessarily cause symptoms or a drop in ventilatory capacity. Forty-six TDI workers who had developed symptoms reported more long-term symptoms than a comparable number of controls. The difference was significant at the 1% level. Ventilation test records of 61 TDI workers who had developed symptoms were available since it was possible to use the records of men who had left the company. The lung function of this group was matched against predicted figures obtained from a control group of 608 subjects living in the same area as the exposed group but not exposed to TDI. It was found that the FEV1 of the affected men was on average 267 ml lower than predicted, and the FVC 269 ml lower. These findings are confirmed by examination of the indivdual records of a futher 20 men.", "contents": "Long-term effects on the health of men engaged in the manufacture of tolylene di-isocyanate. A prospective study of workers engaged in the manufacture of tolylene di-isocyanate (TDI) was carried out over nine years. The study was in two parts: (1) assessment of the symptoms and ventilatory function of men working on the plants who did not complain of respiratory symptoms; (2) assessment of the long-term effects in men who were removed from the plants because of respiratory symptoms. Use of the MRC Questionnaire on Respiratory Symptoms in a group of 76 TDI workers showed no significant differences in symptoms compared with 76 control subjects. Annual lung function tests were carried out on 180 asymptomatic men with possible exposure to TDI. The relationship of the forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) to the height, age, and duration of exposure was examined by linear regression analysis. The equations formulated did not differ significantly from those calculated for non-TDI exposed subjects. Thus exposure to very small concentrations of TDI does not necessarily cause symptoms or a drop in ventilatory capacity. Forty-six TDI workers who had developed symptoms reported more long-term symptoms than a comparable number of controls. The difference was significant at the 1% level. Ventilation test records of 61 TDI workers who had developed symptoms were available since it was possible to use the records of men who had left the company. The lung function of this group was matched against predicted figures obtained from a control group of 608 subjects living in the same area as the exposed group but not exposed to TDI. It was found that the FEV1 of the affected men was on average 267 ml lower than predicted, and the FVC 269 ml lower. These findings are confirmed by examination of the indivdual records of a futher 20 men."} {"id": "PMID:164882", "title": "Studies of the viral flora in keratoconjunctivitis sicca.", "content": "Fifty patients suffering from KCS and exhibiting various patterns of corneal staining with fluorescein were examined for adenovirus types 3, 7, 8, and 14, herpes simplex, and the TRIC group by tissue culture and immunofluorescein techniques. No viruses were detected by either methods, and it is considered that presumption of virus involvement in these cases is untenable.", "contents": "Studies of the viral flora in keratoconjunctivitis sicca. Fifty patients suffering from KCS and exhibiting various patterns of corneal staining with fluorescein were examined for adenovirus types 3, 7, 8, and 14, herpes simplex, and the TRIC group by tissue culture and immunofluorescein techniques. No viruses were detected by either methods, and it is considered that presumption of virus involvement in these cases is untenable."} {"id": "PMID:164883", "title": "Dermatofibrosarcoma protuberans in the parotid gland--a case report.", "content": "A recurrent dermatofibrosarcoma protuberans (storiform fibrocytic histiocytoma) in the parotid gland of a 50-year-old Nigerian male is reported. Recent knowledge of the histiogenetic origin of the tumor is mentioned.", "contents": "Dermatofibrosarcoma protuberans in the parotid gland--a case report. A recurrent dermatofibrosarcoma protuberans (storiform fibrocytic histiocytoma) in the parotid gland of a 50-year-old Nigerian male is reported. Recent knowledge of the histiogenetic origin of the tumor is mentioned."} {"id": "PMID:164884", "title": "Interaction of reduced nicotinamide adenine dinucleotide with beef heart s-malate dehydrogenase.", "content": "The interaction of NADH with s-malate dehydrogenase isolated from beef heart was studied in 20 mM potassium phosphate (pH 6.9)-1 mM EDTA, with forced dialysis, fluorescence, and temperature-jump techniques. Measurements of the change in fluorescence of NADH when it is titrated with enzyme indicate NADH bound to monomeric and dimeric enzyme have different fluorescence yields. These data and the results of direct binding studies can be explained in terms of a model in which the NADH binding sites on dimeric enzyme are equivalent or nearly equivalent, and NADH binding to monomeric enzyme occurs with an affinity very similar to that of the dimer. However, the fluorescence enhancement of NADH on binding to the enzyme is different for the monomer and for each of the two dimer sites.", "contents": "Interaction of reduced nicotinamide adenine dinucleotide with beef heart s-malate dehydrogenase. The interaction of NADH with s-malate dehydrogenase isolated from beef heart was studied in 20 mM potassium phosphate (pH 6.9)-1 mM EDTA, with forced dialysis, fluorescence, and temperature-jump techniques. Measurements of the change in fluorescence of NADH when it is titrated with enzyme indicate NADH bound to monomeric and dimeric enzyme have different fluorescence yields. These data and the results of direct binding studies can be explained in terms of a model in which the NADH binding sites on dimeric enzyme are equivalent or nearly equivalent, and NADH binding to monomeric enzyme occurs with an affinity very similar to that of the dimer. However, the fluorescence enhancement of NADH on binding to the enzyme is different for the monomer and for each of the two dimer sites."} {"id": "PMID:164885", "title": "Conformational flexibility of angiotensin II. A carbon-13 spin-lattice relaxation study.", "content": "Carbon-13 spin-lattice relaxation times (T1) have been determined for the carbon in the octapeptide hormone [5-isoleucine]-angiotensin II in aqueous solution. Two possible models for molecular motion are considered: isotropic overall motion of the hormone with internal motion of some residues and anisotropic overall molecular motion. The data are interpreted in detail using the former model. The alpha carbons of the peptide backbone are all equally restricted in their motion. The correlation time for overall molecular reorientation, calculated from an everage T1 value of 95 msec for the alpha carbons in the peptide backbone, is ca. 5 times 10-10 sec. The carbons in the side chains are more mobile than those in the peptide backbone, with the exception of the side chain of the Tyr residue which does not undergo rapid segmental motion. We propose that [5-isoleucine]-angiotensin II has a restricted backbone conformation and that the alpha carbons of the N- and C-terminal residues are constrained to nearly the same extent as the remaining alpha carbons in the peptide backbone. Chemical shift data indicate that the Pro residue adopts the trans conformation about the His-Pro bond and that the imidazole ring of His has a strong preference for the N-tau -H tautomer.", "contents": "Conformational flexibility of angiotensin II. A carbon-13 spin-lattice relaxation study. Carbon-13 spin-lattice relaxation times (T1) have been determined for the carbon in the octapeptide hormone [5-isoleucine]-angiotensin II in aqueous solution. Two possible models for molecular motion are considered: isotropic overall motion of the hormone with internal motion of some residues and anisotropic overall molecular motion. The data are interpreted in detail using the former model. The alpha carbons of the peptide backbone are all equally restricted in their motion. The correlation time for overall molecular reorientation, calculated from an everage T1 value of 95 msec for the alpha carbons in the peptide backbone, is ca. 5 times 10-10 sec. The carbons in the side chains are more mobile than those in the peptide backbone, with the exception of the side chain of the Tyr residue which does not undergo rapid segmental motion. We propose that [5-isoleucine]-angiotensin II has a restricted backbone conformation and that the alpha carbons of the N- and C-terminal residues are constrained to nearly the same extent as the remaining alpha carbons in the peptide backbone. Chemical shift data indicate that the Pro residue adopts the trans conformation about the His-Pro bond and that the imidazole ring of His has a strong preference for the N-tau -H tautomer."} {"id": "PMID:164886", "title": "Purification of the sex steroid binding protein from human serum.", "content": "The sex steroid binding protein from human pregnancy serum was purified to homogeneity by affinity chromatography and preparative polyacrylamide gel electrophoresis. The selective adsorbants were prepared by coupling [3H]-5alpha-dihydrotestosterone 17beta-hemisuccinate to 3,3'-diaminodipropylamine-agarose, poly(Lys-DLAla)-agarose, and albumin-agarose. The most effective adsorbant purifying for the binding protein was 5alpha-dihydrotestosterone 17beta-hemisuccinyl-3,3'-diaminodipropylamine-agarose. A preparative procedure with 5alpha-dihydrotestosterone 17beta-hemisuccinyl-3,3'-diaminodipropylamine-agarose yielded active material which was further purified by preparative polyacrylamide electrophoresis at pH 9.5. Homogeneity was shown by analytical disc gel electrophoresis at three different pH units. A single radioactive band corresponding to the stained band was shown by incubating with [1,2-3H]-5alpha-dihydrotestosterone prior to electrophoresis. The radioactive peak corresponding to the pure sex steroid binding protein could not be detected when a 100-fold excess of 17beta-estradiol was present in the incubation prior to electrophoresis demonstrating the specific sex steroid binding properties of this protein. The migration of this peak was identical with that obtained when diluted serum was electrophoresed under the same conditions in the presence of [1,2-3H]-5alpha-dihydrotestosterone indicating that no significant changes in the molecular characteristics of the binding protein occurred during the purification procedure. The presence of carbohydrate in the pure protein was shown by the periodic acid-Schiff reagent procedure. Selective adsorbants containing 17beta-estradiol linked at the 3 position were ineffective in retaining sex steroid binding protein activity.", "contents": "Purification of the sex steroid binding protein from human serum. The sex steroid binding protein from human pregnancy serum was purified to homogeneity by affinity chromatography and preparative polyacrylamide gel electrophoresis. The selective adsorbants were prepared by coupling [3H]-5alpha-dihydrotestosterone 17beta-hemisuccinate to 3,3'-diaminodipropylamine-agarose, poly(Lys-DLAla)-agarose, and albumin-agarose. The most effective adsorbant purifying for the binding protein was 5alpha-dihydrotestosterone 17beta-hemisuccinyl-3,3'-diaminodipropylamine-agarose. A preparative procedure with 5alpha-dihydrotestosterone 17beta-hemisuccinyl-3,3'-diaminodipropylamine-agarose yielded active material which was further purified by preparative polyacrylamide electrophoresis at pH 9.5. Homogeneity was shown by analytical disc gel electrophoresis at three different pH units. A single radioactive band corresponding to the stained band was shown by incubating with [1,2-3H]-5alpha-dihydrotestosterone prior to electrophoresis. The radioactive peak corresponding to the pure sex steroid binding protein could not be detected when a 100-fold excess of 17beta-estradiol was present in the incubation prior to electrophoresis demonstrating the specific sex steroid binding properties of this protein. The migration of this peak was identical with that obtained when diluted serum was electrophoresed under the same conditions in the presence of [1,2-3H]-5alpha-dihydrotestosterone indicating that no significant changes in the molecular characteristics of the binding protein occurred during the purification procedure. The presence of carbohydrate in the pure protein was shown by the periodic acid-Schiff reagent procedure. Selective adsorbants containing 17beta-estradiol linked at the 3 position were ineffective in retaining sex steroid binding protein activity."} {"id": "PMID:164887", "title": "Studies on interaction between histone V (f2c) and deoxyribonucleic acids.", "content": "Histone V (2fc) from chick erythroctes was used in the study of its interaction with DNA from various sources. Complexes between this histone and DNA were formed using the procedure of continuous NaCl gradient dialysis in urea. Two physical methods, namely thermal denaturation and circular dichroism (CD), were used as analytical tools. Thermal denaturation of nucleohistone V with chick or calf thymus DNA shows three melting bands: band I at 45-50 degrees corresponds to free base pairs; band II at 75-79 degrees, and band III at 90-93 degrees correspond to histone-bound base pairs. In histone-bound regions, there are 1.5 amino acid residues/nucleotide in nucleohistone V. In contrast, a value between 2.9 and 3.3 was determined for nucleohistone I (fl) (H. J. Li (1973), Biopolymers 12, 287). Similar melting properties have been observed for histone V complexed with bacterial DNA from Micrococcus luteus. Histone V binding to DNA induces a slight transition from a B-type CD spectrum to a C-type spectrum. Trypsin treatment of nucleohistone V reduces melting band III much more effectively than band II. Such a treatment also restores DNA to B conformation in the free state. Reduction of the melting bands of nucleohistone V by polylysine binding follows the order of I greater than II greater than III, accompanied by the increase of a new band at 100 degrees. When two bacterial DNAs of varied A + T (adenine + thymine) content simultaneously compete for the binding of histone V, the more (A \" T)-rich DNA is selectively favored. Under experimental conditions described here, Clostridium perfringens DNA with 69% A + T is bound by histone V in preference to chicken DNA with 56% A + T although the latter has natural sequences for histone V binding.", "contents": "Studies on interaction between histone V (f2c) and deoxyribonucleic acids. Histone V (2fc) from chick erythroctes was used in the study of its interaction with DNA from various sources. Complexes between this histone and DNA were formed using the procedure of continuous NaCl gradient dialysis in urea. Two physical methods, namely thermal denaturation and circular dichroism (CD), were used as analytical tools. Thermal denaturation of nucleohistone V with chick or calf thymus DNA shows three melting bands: band I at 45-50 degrees corresponds to free base pairs; band II at 75-79 degrees, and band III at 90-93 degrees correspond to histone-bound base pairs. In histone-bound regions, there are 1.5 amino acid residues/nucleotide in nucleohistone V. In contrast, a value between 2.9 and 3.3 was determined for nucleohistone I (fl) (H. J. Li (1973), Biopolymers 12, 287). Similar melting properties have been observed for histone V complexed with bacterial DNA from Micrococcus luteus. Histone V binding to DNA induces a slight transition from a B-type CD spectrum to a C-type spectrum. Trypsin treatment of nucleohistone V reduces melting band III much more effectively than band II. Such a treatment also restores DNA to B conformation in the free state. Reduction of the melting bands of nucleohistone V by polylysine binding follows the order of I greater than II greater than III, accompanied by the increase of a new band at 100 degrees. When two bacterial DNAs of varied A + T (adenine + thymine) content simultaneously compete for the binding of histone V, the more (A \" T)-rich DNA is selectively favored. Under experimental conditions described here, Clostridium perfringens DNA with 69% A + T is bound by histone V in preference to chicken DNA with 56% A + T although the latter has natural sequences for histone V binding."} {"id": "PMID:164888", "title": "The assay and isolation of DNA rings using an ATP-dependent endonuclease.", "content": "The ATP-dependent endonuclease from Hemophilus influenzae is relatively inactive on closed or open DNA rings, yet rapidly hydrolyzes single- or double-chained linear DNA. This enzyme in combination with an exonuclease (exo VII) has been shown to spare various circular DNA molecules including those having single-chain regions of significant length. However, rings containing single-chained regions are broken at a rate depending on the length of these regions. By admixing a linear DNA of alternate radiolabel, a simple assay for DNA rings has been developed. The application of this procedure to the assay of folded rings from Drosophila DNA is demonstrated.", "contents": "The assay and isolation of DNA rings using an ATP-dependent endonuclease. The ATP-dependent endonuclease from Hemophilus influenzae is relatively inactive on closed or open DNA rings, yet rapidly hydrolyzes single- or double-chained linear DNA. This enzyme in combination with an exonuclease (exo VII) has been shown to spare various circular DNA molecules including those having single-chain regions of significant length. However, rings containing single-chained regions are broken at a rate depending on the length of these regions. By admixing a linear DNA of alternate radiolabel, a simple assay for DNA rings has been developed. The application of this procedure to the assay of folded rings from Drosophila DNA is demonstrated."} {"id": "PMID:164889", "title": "Partial reconstitution of active ribosomes and 50S subunits.", "content": "Escherichia coli ribosomes and their 50S subunits disassembled by LiCl treatment can be reconstituted into structurally completed but inactive particles. However, peptidyltransferase and polyphenylalanine synthesizing activity can be partly recovered by the addition of methanol to the reconstitution system. Furthermore, entirely active ribosomes and 50S subunits are reconstituted when methanol is present during the initial treatment with LiCl to disassemble the ribosomal components. The presence of methanol (10% v/v) during this treatment diminished the release of some proteins but does not affect the separation of the 5S RNA.", "contents": "Partial reconstitution of active ribosomes and 50S subunits. Escherichia coli ribosomes and their 50S subunits disassembled by LiCl treatment can be reconstituted into structurally completed but inactive particles. However, peptidyltransferase and polyphenylalanine synthesizing activity can be partly recovered by the addition of methanol to the reconstitution system. Furthermore, entirely active ribosomes and 50S subunits are reconstituted when methanol is present during the initial treatment with LiCl to disassemble the ribosomal components. The presence of methanol (10% v/v) during this treatment diminished the release of some proteins but does not affect the separation of the 5S RNA."} {"id": "PMID:164890", "title": "Structures of gangliosides from bovine adrenal medulla.", "content": "Five gangliosides, accounting for over 95% of the total ganglioside fraction, were isolated from bovine adrenal medulla by preparative thin-layer chromatography and the carbohydrate structures determined by a combination of periodate oxidation and permethylation techniques. Partially methylated alditol acetates were generated from the neutral sugars of the fully methylated glycolipids and identified by gas-liquid chromatography. Substitution on N-acetylgalactosamine was determined by methanolysis of the permethylated ganglioside, acetylation of the products, and identification of the resulting substituted methyl glycosides by GLC. Periodate oxidation followed by borohydride reduction confirmed some of the linkages and demonstrated the absence of (2-8) linkages between sialic acid units. Mass spectrometry of the permethylated gangliosides gave information on sugar sequence at the nonreducing end.", "contents": "Structures of gangliosides from bovine adrenal medulla. Five gangliosides, accounting for over 95% of the total ganglioside fraction, were isolated from bovine adrenal medulla by preparative thin-layer chromatography and the carbohydrate structures determined by a combination of periodate oxidation and permethylation techniques. Partially methylated alditol acetates were generated from the neutral sugars of the fully methylated glycolipids and identified by gas-liquid chromatography. Substitution on N-acetylgalactosamine was determined by methanolysis of the permethylated ganglioside, acetylation of the products, and identification of the resulting substituted methyl glycosides by GLC. Periodate oxidation followed by borohydride reduction confirmed some of the linkages and demonstrated the absence of (2-8) linkages between sialic acid units. Mass spectrometry of the permethylated gangliosides gave information on sugar sequence at the nonreducing end."} {"id": "PMID:164891", "title": "Structure-function relationships in glucagon: properties of highly purified des-His-1-, monoiodo-, and (des-Asn-28, Thr-29)(homoserine lactone-27)-glucagon.", "content": "We have compared the ability of glucagon and three highly purified derivatives of the hormone to activate hepatic adenylate cyclase (an expression of biological activity of the hormone) and to compete with [125]glucagon for binding to sites specific for glucagon in hepatic plasma membranes. Relative to that of glucagon, biological activity and affinity of [des-Asn-28,Thr-29](homoserine lactone-27)-glucagon, prepared by CNBr treatment of glucagon, were reduced equally by 40- to 50-fold. By contrast, des-His-1-glucagon, prepared by an insoluble Edman reagent and highly purified (less than 0.5% contamination with native glucagon), displayed a 15-fold decrease in affinity but a 50-fold decrease in biological activity relative to that of the native hormone. At maximal stimulating concentrations, des-His-1-glucagon yielded 70% of the activity given by saturating concentrations of glucagon. Thus, des-His-1-glucagon can be classified as a partial weak agonist. Highly purified monoiodoglucagon and native glucagon displayed identical biological activity and affinity for the binding sites. Our findings suggest that the hydrophilic residues at the terminus of the carboxy region of glucagon are involved in the process of recognition at the glucagon receptor but do not participate in the sequence of events leading to activation of adenylate cyclase. The amino-terminal histidyl residue in glucagon plays an important but not obligatory role in the expression of hormone action and contributes to a significant extent in the recognition process.", "contents": "Structure-function relationships in glucagon: properties of highly purified des-His-1-, monoiodo-, and (des-Asn-28, Thr-29)(homoserine lactone-27)-glucagon. We have compared the ability of glucagon and three highly purified derivatives of the hormone to activate hepatic adenylate cyclase (an expression of biological activity of the hormone) and to compete with [125]glucagon for binding to sites specific for glucagon in hepatic plasma membranes. Relative to that of glucagon, biological activity and affinity of [des-Asn-28,Thr-29](homoserine lactone-27)-glucagon, prepared by CNBr treatment of glucagon, were reduced equally by 40- to 50-fold. By contrast, des-His-1-glucagon, prepared by an insoluble Edman reagent and highly purified (less than 0.5% contamination with native glucagon), displayed a 15-fold decrease in affinity but a 50-fold decrease in biological activity relative to that of the native hormone. At maximal stimulating concentrations, des-His-1-glucagon yielded 70% of the activity given by saturating concentrations of glucagon. Thus, des-His-1-glucagon can be classified as a partial weak agonist. Highly purified monoiodoglucagon and native glucagon displayed identical biological activity and affinity for the binding sites. Our findings suggest that the hydrophilic residues at the terminus of the carboxy region of glucagon are involved in the process of recognition at the glucagon receptor but do not participate in the sequence of events leading to activation of adenylate cyclase. The amino-terminal histidyl residue in glucagon plays an important but not obligatory role in the expression of hormone action and contributes to a significant extent in the recognition process."} {"id": "PMID:164892", "title": "The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates.", "content": "Electron spin resonance spectra are observed during the enzymatic reduction of many nitrophenyl derivatives by rat hepatic microsomes or mitochondria. The spectra indicate that nitroaromatic anion radicals are present and are freely rotating in aqueous solution at a steady-state concentration of 0.1-6 muM. The rate of formation of p-nitrobenzoate (NBZO) dianion radical in microsomal incubates is consistent with the radical being an obligate intermediate in the reduction of NBZO to p-aminobenzoic acid. A model system consisting of NBZO, NADPH, and FMN, but no heme-containing compounds, also reduced NBZO to the NBZO dianion free radical. The steady-state concentration of the anion radicals in microsomal systems is not altered by CO. This observation, together with the results from the model system, suggests that the formation of nitroaromatic anion radicals is mediated through a flavine and not cytochrome P-450. The oxidation of the anion radical intermediate by O2 to the parent nitro compound is proposed to account for the well-known O2 inhibition of microsomal nitroreductase.", "contents": "The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates. Electron spin resonance spectra are observed during the enzymatic reduction of many nitrophenyl derivatives by rat hepatic microsomes or mitochondria. The spectra indicate that nitroaromatic anion radicals are present and are freely rotating in aqueous solution at a steady-state concentration of 0.1-6 muM. The rate of formation of p-nitrobenzoate (NBZO) dianion radical in microsomal incubates is consistent with the radical being an obligate intermediate in the reduction of NBZO to p-aminobenzoic acid. A model system consisting of NBZO, NADPH, and FMN, but no heme-containing compounds, also reduced NBZO to the NBZO dianion free radical. The steady-state concentration of the anion radicals in microsomal systems is not altered by CO. This observation, together with the results from the model system, suggests that the formation of nitroaromatic anion radicals is mediated through a flavine and not cytochrome P-450. The oxidation of the anion radical intermediate by O2 to the parent nitro compound is proposed to account for the well-known O2 inhibition of microsomal nitroreductase."} {"id": "PMID:164893", "title": "Iodohexestrols. II. Characterization of the binding and estrogenic activity of iodinated hexestrol derivatives, in vitro and in vivo.", "content": "The affinity of ortho-iodinated hexestrols for the estrogen binding protein from rat uterus, determined by competitive binding assay, decreases with progressive iodine substitution; 3-iodohexestrol (I-Hex) has a binding affinity 42% that of estradiol. Analysis of [3-H]-I-Hex binding in rat uterine cytosol by sucrose density gradient centrifugation shows both an estrogen-specific binding component (8 S) and a more abundant component (4 S) that is not estrogen specific. Scatchard analysis indicates that this latter binding is of high affinity (Kd equals to 3.7-8.3 times 10- minus-9 M) but is not uterine specific. Polyacrylamide gel electrophoresis shows that most of the [3-H]-I-Hex binding activity in serum and uterine cytosol is distinct from and anodic to the principal protein component (albumin), and that is comigrates with [14-C]thyroxine binding activity. In in vitro incubation of rat uteri, I-Hex can block the specific uptake of [3-H]estradiol into the nuclear fraction; it itself causes a translocation of estrogen-specific binding capacity (as measured by exchange) from cytoplasm to nuclei, and can induce the synthesis of an estrogen-specific uterine protein, all under conditions where it is not metabolically deiodinated to hexestrol. The uterotrophic activities of the iodohexestrols are in most cases comparable to that expected on the basis of their competitive binding affinities. However, selective, estrogen-specific uptake of [3-H]-I-Hex into rat uterus, either in vitro or in vivo, cannot be demonstrated.", "contents": "Iodohexestrols. II. Characterization of the binding and estrogenic activity of iodinated hexestrol derivatives, in vitro and in vivo. The affinity of ortho-iodinated hexestrols for the estrogen binding protein from rat uterus, determined by competitive binding assay, decreases with progressive iodine substitution; 3-iodohexestrol (I-Hex) has a binding affinity 42% that of estradiol. Analysis of [3-H]-I-Hex binding in rat uterine cytosol by sucrose density gradient centrifugation shows both an estrogen-specific binding component (8 S) and a more abundant component (4 S) that is not estrogen specific. Scatchard analysis indicates that this latter binding is of high affinity (Kd equals to 3.7-8.3 times 10- minus-9 M) but is not uterine specific. Polyacrylamide gel electrophoresis shows that most of the [3-H]-I-Hex binding activity in serum and uterine cytosol is distinct from and anodic to the principal protein component (albumin), and that is comigrates with [14-C]thyroxine binding activity. In in vitro incubation of rat uteri, I-Hex can block the specific uptake of [3-H]estradiol into the nuclear fraction; it itself causes a translocation of estrogen-specific binding capacity (as measured by exchange) from cytoplasm to nuclei, and can induce the synthesis of an estrogen-specific uterine protein, all under conditions where it is not metabolically deiodinated to hexestrol. The uterotrophic activities of the iodohexestrols are in most cases comparable to that expected on the basis of their competitive binding affinities. However, selective, estrogen-specific uptake of [3-H]-I-Hex into rat uterus, either in vitro or in vivo, cannot be demonstrated."} {"id": "PMID:164894", "title": "Steroidal 21-diazo ketones: photogenerated corticosteroid receptor labels.", "content": "The 21-diazo derivatives of 9 alpha-fluoro- and 9 alpha-bromo-21 deoxycorticosterone, 21-deoxycorticosterone, and progesterone were synthesized for use as photoaffinity labels for corticosteroid receptors. In the isolated toad bladder system, 9 alpha-bromo-21-diazo-21-deoxycorticosterone was as active as d-aldosterone and more active than 9 alpha-fluoro-cortisol in augmenting active Na+ transport. The activities of 21-diazoprogesterone and progesterone were equal; both were much less potent than d-aldosterone, however. These results indicate that the 21-diazo derivatives had significant functional activity in the toad bladder system. The rat kidney slice system was used to estimate the relative affinities of the diazo steroids for aldosterone receptor sites by competition experiments. At 100-fold excess of competitor to [3-H]aldosterone, the order of affinities was 9 alpha-fluoro-21-diazo-21-deoxycorticosterone greater than 9 alpha-bromo-21-diazo-21-deoxycorticosterone greater than 21-diazoprogesterone. Moreover, 9 alpha-bromo-21-diazo-21-deoxycorticosterone reduced binding of [3-H]aldosterone to cytoplasmic and nuclear forms of the receptor proportionately. On the basis of competition for [3-H]corticosterone binding, presumably to corticosteroid-binding globulin (CBG), the order of affinities was 21-diazo-21-deoxycorticosterone greater than 21-diazoprogesterone greater than 9 alpha-bromo-21-diazo-21-deoxycorticosterone. These findings indicate that 21-diazo steroids may be suitable as photogenerated affinity labels for mineralocorticoid receptors. The tritiated derivative, [1,2-3-H]-9 alpha-bromo-21-diazo-21-deoxycorticosterone (specific activity 25 Ci/mol) was synthesized and used in model experiments on photogenerated covalent binding to rat plasma proteins. Irradiation with uv light resulted in binding of [1,2-3-H]-9 alpha-bromo-21-diazo-21-deoxycorticosterone to plasma proteins, that was resistant to extraction with methylene dichloride and did not exchange with unlabeled corticosterone. The diazocorticosteroids, therefore, may have the requisite functional and selectivity properties for photoaffinity labeling of corticosteroid-binding proteins. Further studies are needed, however, to assure that photogenerated labeling with these steroids was site specific.", "contents": "Steroidal 21-diazo ketones: photogenerated corticosteroid receptor labels. The 21-diazo derivatives of 9 alpha-fluoro- and 9 alpha-bromo-21 deoxycorticosterone, 21-deoxycorticosterone, and progesterone were synthesized for use as photoaffinity labels for corticosteroid receptors. In the isolated toad bladder system, 9 alpha-bromo-21-diazo-21-deoxycorticosterone was as active as d-aldosterone and more active than 9 alpha-fluoro-cortisol in augmenting active Na+ transport. The activities of 21-diazoprogesterone and progesterone were equal; both were much less potent than d-aldosterone, however. These results indicate that the 21-diazo derivatives had significant functional activity in the toad bladder system. The rat kidney slice system was used to estimate the relative affinities of the diazo steroids for aldosterone receptor sites by competition experiments. At 100-fold excess of competitor to [3-H]aldosterone, the order of affinities was 9 alpha-fluoro-21-diazo-21-deoxycorticosterone greater than 9 alpha-bromo-21-diazo-21-deoxycorticosterone greater than 21-diazoprogesterone. Moreover, 9 alpha-bromo-21-diazo-21-deoxycorticosterone reduced binding of [3-H]aldosterone to cytoplasmic and nuclear forms of the receptor proportionately. On the basis of competition for [3-H]corticosterone binding, presumably to corticosteroid-binding globulin (CBG), the order of affinities was 21-diazo-21-deoxycorticosterone greater than 21-diazoprogesterone greater than 9 alpha-bromo-21-diazo-21-deoxycorticosterone. These findings indicate that 21-diazo steroids may be suitable as photogenerated affinity labels for mineralocorticoid receptors. The tritiated derivative, [1,2-3-H]-9 alpha-bromo-21-diazo-21-deoxycorticosterone (specific activity 25 Ci/mol) was synthesized and used in model experiments on photogenerated covalent binding to rat plasma proteins. Irradiation with uv light resulted in binding of [1,2-3-H]-9 alpha-bromo-21-diazo-21-deoxycorticosterone to plasma proteins, that was resistant to extraction with methylene dichloride and did not exchange with unlabeled corticosterone. The diazocorticosteroids, therefore, may have the requisite functional and selectivity properties for photoaffinity labeling of corticosteroid-binding proteins. Further studies are needed, however, to assure that photogenerated labeling with these steroids was site specific."} {"id": "PMID:164895", "title": "Physicochemical characterization of Rhesus low density lipoproteins.", "content": "The serum low density lipoprotein (LDL; p 1.019-1.050 g/ml) of the normal Macaca mulatta monkey (rhesus), kept on a low-fat Purina primate chow diet, was isolated by ultracentrifugal flotation, and its physicochemical properties were compared with those previously reported for human LDL. Rhesus LDL was found to be chemically similar to human LDL. The values for the sedimentation (S25, w-O) and diffusion (D25,w-O) coefficients were 7.09 S and 2.50 times 10- minus-7 cm-2 sec- minus-1, respectively. The intrinsic viscosity was 3.40 ml g- minus-1. The partial specific volume of rhesus LDL, determined in an Anton Paar precision density meter, was 0.960 ml g- minus-1. Molecular weights, calculated from a combination of S-O and D-O and of S-O and [n], were in agreement with the weight-average molecular weight, Mw, of 2.29 times 10-6 obtained by high-speed sedimentation equilibrium. In addition, a Z-average molecular weight, Mz, of 2.73 times 10-6 was calculated because curvature in the graphs of log c vs. r-2 indicated that rhesus LDL was heterogeneous. From the frictional ratio of 1.02, a maximum hydration of 0.1 g of H2O/g of lipoprotein was obtained. On electron micrographs, rhesus LDL appeared spherical with a mean diameter of 196 A, which was substantiated by hydrodynamic analysis.", "contents": "Physicochemical characterization of Rhesus low density lipoproteins. The serum low density lipoprotein (LDL; p 1.019-1.050 g/ml) of the normal Macaca mulatta monkey (rhesus), kept on a low-fat Purina primate chow diet, was isolated by ultracentrifugal flotation, and its physicochemical properties were compared with those previously reported for human LDL. Rhesus LDL was found to be chemically similar to human LDL. The values for the sedimentation (S25, w-O) and diffusion (D25,w-O) coefficients were 7.09 S and 2.50 times 10- minus-7 cm-2 sec- minus-1, respectively. The intrinsic viscosity was 3.40 ml g- minus-1. The partial specific volume of rhesus LDL, determined in an Anton Paar precision density meter, was 0.960 ml g- minus-1. Molecular weights, calculated from a combination of S-O and D-O and of S-O and [n], were in agreement with the weight-average molecular weight, Mw, of 2.29 times 10-6 obtained by high-speed sedimentation equilibrium. In addition, a Z-average molecular weight, Mz, of 2.73 times 10-6 was calculated because curvature in the graphs of log c vs. r-2 indicated that rhesus LDL was heterogeneous. From the frictional ratio of 1.02, a maximum hydration of 0.1 g of H2O/g of lipoprotein was obtained. On electron micrographs, rhesus LDL appeared spherical with a mean diameter of 196 A, which was substantiated by hydrodynamic analysis."} {"id": "PMID:164896", "title": "The specificity of different classes of ethylating agents toward various sites of HeLa cell DNA in vitro and in vivo.", "content": "The sites and extent of ethyl products of neutral ethylation of HeLa cell DNA by [14-C]diethyl sulfate, [14-C]ethyl methanesulfonate, and [14-C]ethylnitrosourea have been determined in vitro and in vivo, and found to differ significantly depending on the ethylating agents. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of HeLa cell DNA in the following order: 7-ethylguanine greater than 3-ethyladenine greater than 1-ethyladenine, 7-ethyladenine greater than 3-ethylguanine, 3-ethylcytosine, O-6-ethylguanine. Ethyl bases accounted for 84-87% of the total ethyl groups associated with HeLa cell DNA. Ethylnitrosourea, in contrast, has particular affinity for the O-6 position of guanine. It ethylates the bases of HeLa cell DNA in the following order: O-6-ethylguanine, 7-ethylguanine greater than 3-ethyladenine greater than 3-ethylguanine, 3-ethylthymine greater than 1-ethyladenine, 7-ethyladenine, 3-ethylcytosine. Ethylation of the bases only accounts for 30% of the total ethylation in the case of ethylnitrosourea. The remaining 70% of the [14-C]ethyl groups, introduced in vivo and in vitro, are in the form of phosphotriesters which after perchloric acid hydrolysis are found as [14-CA1ethanol and [14-C]ethyl phosphate. In contrast, phosphotriesters amounted to only 8-20% of total ethylation in in vivo or in vitro diethyl sulfate and ethyl methanesulfonate treated HeLa cell DNA, and 25% of the total methylation in in vitro methylnitrosourea treated HeLa cell DNA. Alkylation at the N-7 and N-3 positions of purines in DNA destabilizes the glycosidic linkages. Part of 7-ethylguanine and 3-ethyladenine are found to be spontaneously released during the ethylation reaction. Incorporation of the 14-C of the alkylating agents into normal DNA bases of HeLa cells can be eliminated by performing the alkylations, in the presence of cytosine arabinoside, for 1 hr.", "contents": "The specificity of different classes of ethylating agents toward various sites of HeLa cell DNA in vitro and in vivo. The sites and extent of ethyl products of neutral ethylation of HeLa cell DNA by [14-C]diethyl sulfate, [14-C]ethyl methanesulfonate, and [14-C]ethylnitrosourea have been determined in vitro and in vivo, and found to differ significantly depending on the ethylating agents. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of HeLa cell DNA in the following order: 7-ethylguanine greater than 3-ethyladenine greater than 1-ethyladenine, 7-ethyladenine greater than 3-ethylguanine, 3-ethylcytosine, O-6-ethylguanine. Ethyl bases accounted for 84-87% of the total ethyl groups associated with HeLa cell DNA. Ethylnitrosourea, in contrast, has particular affinity for the O-6 position of guanine. It ethylates the bases of HeLa cell DNA in the following order: O-6-ethylguanine, 7-ethylguanine greater than 3-ethyladenine greater than 3-ethylguanine, 3-ethylthymine greater than 1-ethyladenine, 7-ethyladenine, 3-ethylcytosine. Ethylation of the bases only accounts for 30% of the total ethylation in the case of ethylnitrosourea. The remaining 70% of the [14-C]ethyl groups, introduced in vivo and in vitro, are in the form of phosphotriesters which after perchloric acid hydrolysis are found as [14-CA1ethanol and [14-C]ethyl phosphate. In contrast, phosphotriesters amounted to only 8-20% of total ethylation in in vivo or in vitro diethyl sulfate and ethyl methanesulfonate treated HeLa cell DNA, and 25% of the total methylation in in vitro methylnitrosourea treated HeLa cell DNA. Alkylation at the N-7 and N-3 positions of purines in DNA destabilizes the glycosidic linkages. Part of 7-ethylguanine and 3-ethyladenine are found to be spontaneously released during the ethylation reaction. Incorporation of the 14-C of the alkylating agents into normal DNA bases of HeLa cells can be eliminated by performing the alkylations, in the presence of cytosine arabinoside, for 1 hr."} {"id": "PMID:164897", "title": "Different cyclic adenosine 3',5'-monophosphate requirements for induction of beta-galactosidase and tryptophanase. Effect of osmotic pressure on intracellular cyclic adenosine 3,5-monophosphate concentrations.", "content": "In this study we have tried to answer the following questions: (1) is it possible for different catabolite-repressible genes, although submitted to the same control, to be expressed selectively depending upon the growth conditions, and (2) what is the effect of increasing the osmolarity of the medium on the intracellular level of cAMP? Two conditions were found to cause a continuous variation of intracellular cAMP levels during growth. With different strains, higher cAMP levels are required for induction of the tryptophanase gene than one required for induction of the lactose operon. cAMP has been provided externally in adenyl cyclase minus cells of a mutant that has been made permeable by EDTA treatment. Although external cAMP concentrations, 10 times higher than the usual intracellular levels, are required for induction of beta-galactosidase and tryptophanase, the difference of requirements of cAMP is maintained. An increase in the osmolarity of the medium by sucrose addition causes a fourfold decrease in the intracellular cAMP level. As a consequence this prevents the induction of tryptophanase whereas beta-galactosidase is still inducible. After pulse induction, a difference in the kinetics of expression of the tryptophanase and beta-galactosidase genes was found. Its relationship with the previous results is discussed.", "contents": "Different cyclic adenosine 3',5'-monophosphate requirements for induction of beta-galactosidase and tryptophanase. Effect of osmotic pressure on intracellular cyclic adenosine 3,5-monophosphate concentrations. In this study we have tried to answer the following questions: (1) is it possible for different catabolite-repressible genes, although submitted to the same control, to be expressed selectively depending upon the growth conditions, and (2) what is the effect of increasing the osmolarity of the medium on the intracellular level of cAMP? Two conditions were found to cause a continuous variation of intracellular cAMP levels during growth. With different strains, higher cAMP levels are required for induction of the tryptophanase gene than one required for induction of the lactose operon. cAMP has been provided externally in adenyl cyclase minus cells of a mutant that has been made permeable by EDTA treatment. Although external cAMP concentrations, 10 times higher than the usual intracellular levels, are required for induction of beta-galactosidase and tryptophanase, the difference of requirements of cAMP is maintained. An increase in the osmolarity of the medium by sucrose addition causes a fourfold decrease in the intracellular cAMP level. As a consequence this prevents the induction of tryptophanase whereas beta-galactosidase is still inducible. After pulse induction, a difference in the kinetics of expression of the tryptophanase and beta-galactosidase genes was found. Its relationship with the previous results is discussed."} {"id": "PMID:164898", "title": "The role of superoxide radical in the autoxidation of cytochrome c.", "content": "The net rate of autoxidation of ferrocytochrome c was decreased by ferricytochrome c. Superoxide dismutase accelerated this autoxidation to a limit and overcame the inhibitory effect of ferricytochrome c. This was the case whether the autoxidationwas observed in the presence or in the absence of denaturants, such as alcohols orurea, and whether the superoxide dismutase used was the Cu-2+-Zn-2+ enzyme from bovine erythrocytes or the Mn-3+-enzyme from Escherichia coli. It can be deduced that the autoxidation of ferrocytochrome c, under a variety of conditions, geenerates O2 minus which can then dismute to H202 + O2 or can reduce ferricytochrome c back to ferrocytochrome c. Superoxide dismutase, by accelerating the dismutation of O2 minus, prevents the back reaction and thus exposes the true rate of reaction of ferrocytochrome c with molecular oxygen.", "contents": "The role of superoxide radical in the autoxidation of cytochrome c. The net rate of autoxidation of ferrocytochrome c was decreased by ferricytochrome c. Superoxide dismutase accelerated this autoxidation to a limit and overcame the inhibitory effect of ferricytochrome c. This was the case whether the autoxidationwas observed in the presence or in the absence of denaturants, such as alcohols orurea, and whether the superoxide dismutase used was the Cu-2+-Zn-2+ enzyme from bovine erythrocytes or the Mn-3+-enzyme from Escherichia coli. It can be deduced that the autoxidation of ferrocytochrome c, under a variety of conditions, geenerates O2 minus which can then dismute to H202 + O2 or can reduce ferricytochrome c back to ferrocytochrome c. Superoxide dismutase, by accelerating the dismutation of O2 minus, prevents the back reaction and thus exposes the true rate of reaction of ferrocytochrome c with molecular oxygen."} {"id": "PMID:164899", "title": "31-P nuclear magnetic resonance studies on serum low and high density lipoproteins: effect of paramagnetic ion.", "content": "A paramagnetic quenching reagent, Mn-2+/EDTA (1:2.2), was developed for the purpose of investigating the phospholipid phosphate groupings of human serum low and high density lipoproteins through the quenching effect of the reagent on the 31-P nuclear magnetic resonance signals from these complexes. Systems investigated included native low and high density serum liproteins (LDL, HDL2, and HDL3), egg phosphatidylcholine vesicles together with appropriate phosphodiester model systems, diethyl phosphate in aqueous buffer, and phosphatidylcholine and sphingomyelin both in anhydrous methanol. The results of these studies indicated that ca. 50 percent of the phospholipid-phosphorus signal of LDL is quenched upon titration as compared to an 80-85 percent figure observed for HDL2 and HDL3. In all cases the spectral effects were totally reversible upon removalof the paramagnetic ion by dialysis. The results of the titration studies indicated a similar but not an identical behavior between HDL2 and HDL3. The results are consistent with model structures of HDL and LDL particles derived from low angle X-ray diffraction.", "contents": "31-P nuclear magnetic resonance studies on serum low and high density lipoproteins: effect of paramagnetic ion. A paramagnetic quenching reagent, Mn-2+/EDTA (1:2.2), was developed for the purpose of investigating the phospholipid phosphate groupings of human serum low and high density lipoproteins through the quenching effect of the reagent on the 31-P nuclear magnetic resonance signals from these complexes. Systems investigated included native low and high density serum liproteins (LDL, HDL2, and HDL3), egg phosphatidylcholine vesicles together with appropriate phosphodiester model systems, diethyl phosphate in aqueous buffer, and phosphatidylcholine and sphingomyelin both in anhydrous methanol. The results of these studies indicated that ca. 50 percent of the phospholipid-phosphorus signal of LDL is quenched upon titration as compared to an 80-85 percent figure observed for HDL2 and HDL3. In all cases the spectral effects were totally reversible upon removalof the paramagnetic ion by dialysis. The results of the titration studies indicated a similar but not an identical behavior between HDL2 and HDL3. The results are consistent with model structures of HDL and LDL particles derived from low angle X-ray diffraction."} {"id": "PMID:164900", "title": "2'-O-methylated oligonucleotides in ribosomal 18S and 28S RNA of a mouse hepatoma, MH 134.", "content": "Simple two-dimensional thin-layer chromatography was found to be useful for the separation of sugar methylated dinucleotides in RNA. Of the 16 possible sequences of the type Nm-Np, 15 were separated and all the sequences were determined. In a mouse hepatoma, MH 134, the levels of the sugar methylation in the 18S and 28S RNA molecules were 17-18 and 11-12 per 1000 nucleotides, respectively. Thus, 18s RNA contained approximately 35 2'-O-methylated dinucleotides and 28S RNA approximately 60 2'-O-methylated dinucleotides. The pattern of distribution was also distinct between these two molecules. Two 2'-O-methylated trinucleotides were identified in the 28S RNA with the sequences Um-Gm-Up and Um-Gm-psip. A unique 2'-O-methylated tetranucleotide was present also in the 28S RNA, the sequence of which was Am-Gm-Cm-Ap. The 5'-terminal nucleotides of both 18S and 28S RNA were obtained as nucleoside 3',5'-diphosphates (pNp) in the trinucleotide fraction of the RNase T2 digest. The 5'-termimi of 18S and 28S RNA were pUp and pCp, respectively, and found to be almost homogeneous.", "contents": "2'-O-methylated oligonucleotides in ribosomal 18S and 28S RNA of a mouse hepatoma, MH 134. Simple two-dimensional thin-layer chromatography was found to be useful for the separation of sugar methylated dinucleotides in RNA. Of the 16 possible sequences of the type Nm-Np, 15 were separated and all the sequences were determined. In a mouse hepatoma, MH 134, the levels of the sugar methylation in the 18S and 28S RNA molecules were 17-18 and 11-12 per 1000 nucleotides, respectively. Thus, 18s RNA contained approximately 35 2'-O-methylated dinucleotides and 28S RNA approximately 60 2'-O-methylated dinucleotides. The pattern of distribution was also distinct between these two molecules. Two 2'-O-methylated trinucleotides were identified in the 28S RNA with the sequences Um-Gm-Up and Um-Gm-psip. A unique 2'-O-methylated tetranucleotide was present also in the 28S RNA, the sequence of which was Am-Gm-Cm-Ap. The 5'-terminal nucleotides of both 18S and 28S RNA were obtained as nucleoside 3',5'-diphosphates (pNp) in the trinucleotide fraction of the RNase T2 digest. The 5'-termimi of 18S and 28S RNA were pUp and pCp, respectively, and found to be almost homogeneous."} {"id": "PMID:164901", "title": "Nuclear magnetic resonance studies of substrate interaction with cobalt substituted alcohol dehydrogenase from liver.", "content": "The role of zinc in liver alcohol dehydrogenase has been studied by replacement of 1.3 and 3.5 of the four Zn(II) ions with Co(II) and measuring the effects of the paramagnetic Co(II) on the relaxation rates of the protons of water, ethanol, and isobutyramide. Water relaxation studies at 8, 24, 100, and 220 MHz indicate two classes of bound Co(II). The similar to 2 readily replaced Co(II) ions retain one fast exchanging water proton in their inner coordination spheres, while the similar to 2 slowly exchanging Co(II) ions coordinate no detectable water protons, indicating that the former replaced Zn(II) at the \"catalytic sites\" and the latter replaced Zn(II) at the \"structural sites\" detected crystallographically. Ethanol, acetaldehyde, and isobutyramide bind with appropriate affinities to the Co(II) substituted alcohol dehydrogenases decreasing the number of fast exchanging protons at the catalytic Co(II) site by greater than or equal to 54 percent. Coenzyme binding causes smaller changes in the water relaxation rate which may be due to local conformation changes. The paramagnetic effects of Co(II) at the catalytic site on the relaxation rates of the methyl protons of isobutyramide at 100 and 220 MHz indicate that this analog binds at a site 9.1 A from the catalytic Co(II). This distance decreases to 6.9 A when NADH is bound, and a Co(II) to methyne proton distance of 6.6 A is determined indicating a conformation change leading to the formation of a second sphere enzyme-Co(II)-isobutyramide complex in which a hydroxyl or water ligand intervenes between the metal and the substrate analog. Similar behavior is observed in the enzyme-ethanol complexes. The paramagnetic effects of Co(II), at the catalytic site, on the relaxation rates of the protons of ethanol at 100 and 220 MHz, indicate that this substrate bind at a site 12-14 A distant from the catalytic Co(II) but that this distancedecreases to 6.3 A in the abortive enzyme-NADH-ethanol complex. The role of the catalytic Co(II) thus appears to be the activation of a hydroxyl or water ligand which polarizes the aldehyde carbonyl group by hydrogen bonding. The role of the structural Co(II), which is more distant from isobutyramide (9-11 A), may be that of a template for protein conformation changes. By combining the present distances with those from previous magnetic resonance studies on the liver enzyme, the arrangement of coenzyme, metal, and substrate at the active site in solution can be constructed. This arrangement is consistent with that of ADP-ribose and zinc in the crystalline complex of liver alcohol dehydrogenase as determined by X-ray crystallography (Branden et al., (1973), Proc. Natl. Acad. Sci. U.S.A.70, 2439).", "contents": "Nuclear magnetic resonance studies of substrate interaction with cobalt substituted alcohol dehydrogenase from liver. The role of zinc in liver alcohol dehydrogenase has been studied by replacement of 1.3 and 3.5 of the four Zn(II) ions with Co(II) and measuring the effects of the paramagnetic Co(II) on the relaxation rates of the protons of water, ethanol, and isobutyramide. Water relaxation studies at 8, 24, 100, and 220 MHz indicate two classes of bound Co(II). The similar to 2 readily replaced Co(II) ions retain one fast exchanging water proton in their inner coordination spheres, while the similar to 2 slowly exchanging Co(II) ions coordinate no detectable water protons, indicating that the former replaced Zn(II) at the \"catalytic sites\" and the latter replaced Zn(II) at the \"structural sites\" detected crystallographically. Ethanol, acetaldehyde, and isobutyramide bind with appropriate affinities to the Co(II) substituted alcohol dehydrogenases decreasing the number of fast exchanging protons at the catalytic Co(II) site by greater than or equal to 54 percent. Coenzyme binding causes smaller changes in the water relaxation rate which may be due to local conformation changes. The paramagnetic effects of Co(II) at the catalytic site on the relaxation rates of the methyl protons of isobutyramide at 100 and 220 MHz indicate that this analog binds at a site 9.1 A from the catalytic Co(II). This distance decreases to 6.9 A when NADH is bound, and a Co(II) to methyne proton distance of 6.6 A is determined indicating a conformation change leading to the formation of a second sphere enzyme-Co(II)-isobutyramide complex in which a hydroxyl or water ligand intervenes between the metal and the substrate analog. Similar behavior is observed in the enzyme-ethanol complexes. The paramagnetic effects of Co(II), at the catalytic site, on the relaxation rates of the protons of ethanol at 100 and 220 MHz, indicate that this substrate bind at a site 12-14 A distant from the catalytic Co(II) but that this distancedecreases to 6.3 A in the abortive enzyme-NADH-ethanol complex. The role of the catalytic Co(II) thus appears to be the activation of a hydroxyl or water ligand which polarizes the aldehyde carbonyl group by hydrogen bonding. The role of the structural Co(II), which is more distant from isobutyramide (9-11 A), may be that of a template for protein conformation changes. By combining the present distances with those from previous magnetic resonance studies on the liver enzyme, the arrangement of coenzyme, metal, and substrate at the active site in solution can be constructed. This arrangement is consistent with that of ADP-ribose and zinc in the crystalline complex of liver alcohol dehydrogenase as determined by X-ray crystallography (Branden et al., (1973), Proc. Natl. Acad. Sci. U.S.A.70, 2439)."} {"id": "PMID:164902", "title": "Flexibility of coupling and stoichiometry of ATP formation in intact chloroplasts.", "content": "Since coupling between phosphorylation and electron transport cannot be measured directly in intact chloroplasts capable of high rates of photosynthesis, attempts were made to determine ATP/2 e ratios from the quamdum requirements of glycerate and phosphoglycerate reduction and from the extent of oxidation of added NADH via the malate shuttle during reduction of phosphoglycerate in light. These different approaches gave similar results. The quantum requirement of glycerate reduction, which needs 2 molecules of ATP per molecule of NADPH oxidized was found to be pH-dependent. 9-11 quanta were required at pH 7.6, and only about 6 at pH 7.0. The quantum requirement of phosphoglycerate reduction, which consumes ATP and NADPH in a 1/1 ratio, was about 4 both at pH 7.6 ant at 7.0. ATP/2 e ratios calculated from the quantum requirements and the extent of phosphoglycerate accumulation during glycerate reduction were usually between 1.2 and 1.4, occasionally higher, but they never approached 2. Although the chloroplast envelope is impermeable to pyridine nucleotides, illuminated chlrooplasts reduced added NAD via the malate shuttle in the absence of electron acceptors and also during the reduction of glycerate or CO2. When phosphoglycerate was added as the substrate, reduction of pyridine-nucleotides was replaced by oxidation and hydrogen was shuttled into the chloroplasts to be used for phosphoglycerate reduction even under light which was rate-limiting for reduction. This indicated formation of more ATP than NADPH by the electron transport chain. From the rates of oxidation of external NADH and of phosphoglycerate reduction at very low light intensities ATP/2e ratios were calculated to be between 1.1 and 1.4. Fully coupled chloroplasts reduced oxaloacetate in the light at rates reaching 80 and in some instances 130 mumoles times mg-1 chlorophyll times h-1 even though ATP is not consumed in this reaction. The energy transfer inhibitor phlorizin did not significantly suppress this reduction at concentrations which completely inhibited photosynthesis. Uncouplers stimulated oxaloacetate reduction by factors ranging from 1.5 to more than 10. Chloroplasts showing little uncoupler-induced stimulation of oxaloacetate reduction were highly active in photoreducing CO2. Measurements of light intensity dependence of quantum requirements for oxaloacetate reduction gave no indication for the existence of uncoupled or basal electron flow in intact chloroplasts. Rather reduction is brought about by loosely coupled electron transport. It is concluded that coupling of phosphorylation to electron transport in intact chloroplasts is flexible, not tight. Calculated ATP/2e ratios were obtained under con a decreENG", "contents": "Flexibility of coupling and stoichiometry of ATP formation in intact chloroplasts. Since coupling between phosphorylation and electron transport cannot be measured directly in intact chloroplasts capable of high rates of photosynthesis, attempts were made to determine ATP/2 e ratios from the quamdum requirements of glycerate and phosphoglycerate reduction and from the extent of oxidation of added NADH via the malate shuttle during reduction of phosphoglycerate in light. These different approaches gave similar results. The quantum requirement of glycerate reduction, which needs 2 molecules of ATP per molecule of NADPH oxidized was found to be pH-dependent. 9-11 quanta were required at pH 7.6, and only about 6 at pH 7.0. The quantum requirement of phosphoglycerate reduction, which consumes ATP and NADPH in a 1/1 ratio, was about 4 both at pH 7.6 ant at 7.0. ATP/2 e ratios calculated from the quantum requirements and the extent of phosphoglycerate accumulation during glycerate reduction were usually between 1.2 and 1.4, occasionally higher, but they never approached 2. Although the chloroplast envelope is impermeable to pyridine nucleotides, illuminated chlrooplasts reduced added NAD via the malate shuttle in the absence of electron acceptors and also during the reduction of glycerate or CO2. When phosphoglycerate was added as the substrate, reduction of pyridine-nucleotides was replaced by oxidation and hydrogen was shuttled into the chloroplasts to be used for phosphoglycerate reduction even under light which was rate-limiting for reduction. This indicated formation of more ATP than NADPH by the electron transport chain. From the rates of oxidation of external NADH and of phosphoglycerate reduction at very low light intensities ATP/2e ratios were calculated to be between 1.1 and 1.4. Fully coupled chloroplasts reduced oxaloacetate in the light at rates reaching 80 and in some instances 130 mumoles times mg-1 chlorophyll times h-1 even though ATP is not consumed in this reaction. The energy transfer inhibitor phlorizin did not significantly suppress this reduction at concentrations which completely inhibited photosynthesis. Uncouplers stimulated oxaloacetate reduction by factors ranging from 1.5 to more than 10. Chloroplasts showing little uncoupler-induced stimulation of oxaloacetate reduction were highly active in photoreducing CO2. Measurements of light intensity dependence of quantum requirements for oxaloacetate reduction gave no indication for the existence of uncoupled or basal electron flow in intact chloroplasts. Rather reduction is brought about by loosely coupled electron transport. It is concluded that coupling of phosphorylation to electron transport in intact chloroplasts is flexible, not tight. Calculated ATP/2e ratios were obtained under con a decreENG"} {"id": "PMID:164903", "title": "The iron electron-nuclear double resonance (ENDOR) of 4-Fe clusters in iron-sulfur proteins from Chromatium and Clostridium pasteurianum.", "content": "Iron electron-nuclear double resonance (ENDOR) measurements were made of the 4-Fe clusters in oxidized Chromatium high-potential iron-sulfur protein, dithionite-reduced high-potential iron-sulfur protein in 80% dimethylsulphoxide, fully reduced Clostridium pasteurianum ferredoxin in aqueous solution and in 80% dimethylsulfoxide. The hyperfine couplings determined show that: i) the electron distribution in each case is nearly symmetric; ii) there are two types of iron in oxidized high potential iron-sulfur protein; iii) only one type of iron is observed in each fully reduced 4-Fe cluster; iv) the data also suggest a greater electron delocalization onto the ligands as compared to the 2-Fe ferredoxins.", "contents": "The iron electron-nuclear double resonance (ENDOR) of 4-Fe clusters in iron-sulfur proteins from Chromatium and Clostridium pasteurianum. Iron electron-nuclear double resonance (ENDOR) measurements were made of the 4-Fe clusters in oxidized Chromatium high-potential iron-sulfur protein, dithionite-reduced high-potential iron-sulfur protein in 80% dimethylsulphoxide, fully reduced Clostridium pasteurianum ferredoxin in aqueous solution and in 80% dimethylsulfoxide. The hyperfine couplings determined show that: i) the electron distribution in each case is nearly symmetric; ii) there are two types of iron in oxidized high potential iron-sulfur protein; iii) only one type of iron is observed in each fully reduced 4-Fe cluster; iv) the data also suggest a greater electron delocalization onto the ligands as compared to the 2-Fe ferredoxins."} {"id": "PMID:164904", "title": "Studies on the active transfer of reducing equivalents into mitochondria via the malate-aspartate shuttle.", "content": "1. The effects of mitochondrial energy states onthe extramitochondrial NADH/NAD ratio via a reconstituted malate-aspartate shuttle have been investigated. 2. The transfer of reducing equivalents into isolated mitochondria is stimulated by ATP and by electron transport. The effect of ATP is inhibited by oligomycin. The effect of electron transport is inhibited by uncouplers. 3. Uncoupling of the mitochondria is required for rapid transfer of reducing equivalents out of the mitochondria. 4. A glutamate-stimulated entry of aspartate into energized mitochondria suggests that the malate-aspartate shuttle is to some extent reversible even in a high energy state of the mitochondria. 5. It is concluded that the malate-aspartate shuttle contributes to the formation of the skewed redox situation across the inner mitochondrial membrane, which has a more reduced inside.", "contents": "Studies on the active transfer of reducing equivalents into mitochondria via the malate-aspartate shuttle. 1. The effects of mitochondrial energy states onthe extramitochondrial NADH/NAD ratio via a reconstituted malate-aspartate shuttle have been investigated. 2. The transfer of reducing equivalents into isolated mitochondria is stimulated by ATP and by electron transport. The effect of ATP is inhibited by oligomycin. The effect of electron transport is inhibited by uncouplers. 3. Uncoupling of the mitochondria is required for rapid transfer of reducing equivalents out of the mitochondria. 4. A glutamate-stimulated entry of aspartate into energized mitochondria suggests that the malate-aspartate shuttle is to some extent reversible even in a high energy state of the mitochondria. 5. It is concluded that the malate-aspartate shuttle contributes to the formation of the skewed redox situation across the inner mitochondrial membrane, which has a more reduced inside."} {"id": "PMID:164905", "title": "Mitochondria from human term placenta. I. Isolation and assay conditions for oxidative phosphorylation.", "content": "Human term placental mitochondria were resolved by differential centrifugation into three fractions, heavy mitochondria, light mitochondria and a third, less dense fraction. Approximately equal amounts of mitochondrial protein were found in the three fractions. These mitochondrial preparations differed in physical properties. ATPase and \"ADPase\" content and oxidative capacities. Assay conditions were developed which permitted the polarographic measurement of respiration and coupled phosphorylation carried out by all three mitocondrial preparations despite the variable nucleotide-phosphate phosphatase activities present. With heavy mitochondria, rates of respiration were consistently higher than those previously reported for unfractionated placental mitochondria. Respiratory control ratios were comparable to those of mitochondria from other steroid hormone-producing endocrine tissues and ADP/O ratios approaching the theoretical maxima were obtained. Both lighter placental mitochondrial fractions displayed somewhat lower respiration rates and respiratory control but their primary defect was a selective uncoupling of the third site of energy conservation. Modification of isolation procedures were evaluated in terms of quantitative yield and functional activity of the three fractions.", "contents": "Mitochondria from human term placenta. I. Isolation and assay conditions for oxidative phosphorylation. Human term placental mitochondria were resolved by differential centrifugation into three fractions, heavy mitochondria, light mitochondria and a third, less dense fraction. Approximately equal amounts of mitochondrial protein were found in the three fractions. These mitochondrial preparations differed in physical properties. ATPase and \"ADPase\" content and oxidative capacities. Assay conditions were developed which permitted the polarographic measurement of respiration and coupled phosphorylation carried out by all three mitocondrial preparations despite the variable nucleotide-phosphate phosphatase activities present. With heavy mitochondria, rates of respiration were consistently higher than those previously reported for unfractionated placental mitochondria. Respiratory control ratios were comparable to those of mitochondria from other steroid hormone-producing endocrine tissues and ADP/O ratios approaching the theoretical maxima were obtained. Both lighter placental mitochondrial fractions displayed somewhat lower respiration rates and respiratory control but their primary defect was a selective uncoupling of the third site of energy conservation. Modification of isolation procedures were evaluated in terms of quantitative yield and functional activity of the three fractions."} {"id": "PMID:164906", "title": "Multiple molecular forms of phosphoprotein phosphatase. III. Phosphorylase phosphatase and phosphohistone phosphatase of rabbit liver.", "content": "1. Phosphoprotein phosphatase (phosphoprotein phosphohydrolase EC 3.1.3.16) in the soluble fraction of rabbit liver which catalyzes the dephosphorylation of muscle phosphorylase a and phosphohistone (P-histone) was resolved into three active fractions by NaCl gradient elution from a DEAE-cellulose column (Fraction I, 11 and III in order of elution). They have different relative reaction rates for the two substrates and different degrees of stimulation by Mn-2+. Apparent Km values of Fraction I, II and III were 15, 20 and 16 muM for phosphorylase a, and 6.9, 5.3 and 4.4 muM for P-histone, respectively (with Mn-2+ in the assay mixture). 2. On sucrose density gradient centrifugation Fraction I and II were revealed to contain a major peak (7.0 S and 7.8 S, respectively) and a minor peak (4.0 S) of activity, while Fraction III contained only one peak (5.8 S). Freezing and thawing in the presence of 0.2 M mercaptoethanol dissociated all three fractions into subunits of similar molecular size (3.4 S), with concomitant enhancement of phosphorylase phosphatase activity. The Km values all became essentially the same (20 muM for phosphorylase a and 16 muM for P-histone). 3. The phosphorylase phosphatase and P-histone phosphatase activities could not be separated with any of the procedures described. Competition between the two phosphoprotein substrates was observed with some of the fractions.?", "contents": "Multiple molecular forms of phosphoprotein phosphatase. III. Phosphorylase phosphatase and phosphohistone phosphatase of rabbit liver. 1. Phosphoprotein phosphatase (phosphoprotein phosphohydrolase EC 3.1.3.16) in the soluble fraction of rabbit liver which catalyzes the dephosphorylation of muscle phosphorylase a and phosphohistone (P-histone) was resolved into three active fractions by NaCl gradient elution from a DEAE-cellulose column (Fraction I, 11 and III in order of elution). They have different relative reaction rates for the two substrates and different degrees of stimulation by Mn-2+. Apparent Km values of Fraction I, II and III were 15, 20 and 16 muM for phosphorylase a, and 6.9, 5.3 and 4.4 muM for P-histone, respectively (with Mn-2+ in the assay mixture). 2. On sucrose density gradient centrifugation Fraction I and II were revealed to contain a major peak (7.0 S and 7.8 S, respectively) and a minor peak (4.0 S) of activity, while Fraction III contained only one peak (5.8 S). Freezing and thawing in the presence of 0.2 M mercaptoethanol dissociated all three fractions into subunits of similar molecular size (3.4 S), with concomitant enhancement of phosphorylase phosphatase activity. The Km values all became essentially the same (20 muM for phosphorylase a and 16 muM for P-histone). 3. The phosphorylase phosphatase and P-histone phosphatase activities could not be separated with any of the procedures described. Competition between the two phosphoprotein substrates was observed with some of the fractions.?"} {"id": "PMID:164907", "title": "An interpretation of the three line EPR spectrum of nitric oxide hemeproteins and related model systems: the effect of the heme environment.", "content": "The EPR spectra of the nitric oxide (NO) derivatives of structurally perturbed Fe (II) hemeproteins show various patterns, all of which are characterized by the conspicuous three-line hyperfine splitting due to 14NO, in contrast to that of the native proteins. For the purpose of obtaining structural information from these three line spectra, the model systems were studied, which consist of NO, heme (or TPP-Fe(II), where TTP means alpha, beta, gamma, delta-tetraphenylporphine) and the nitrogenous base, pyridine or quinoline, which, respectively, give the native type or the three line (perturbed type) EPR spectrum. The ring proton paramagnetic shift of quinoline in this system shows that it is not coordinated to NO-TPP-Fe(II) as a normal axial ligand, in contrast to pyridine which gives the shift pattern of the ordinary axial ligation. This observation suggests that in the NO-hemeproteins some perturbations of the protein structure cause the rupture or distortion of the bond between the imidazole nitrogen on the fifth coordination site and the heme iron, resulting in the three line spectrum. The EPR study of the model systems, the pentacoordinated complex, NO-heme and NO-TPP-Fe(II), in various media revealed that the pentacoordinated species indeed exhibits, depending upon its environment, a variety of spectra, which closely reproduce the three line patterns observed in the perturbed proteins and some related model systems. Such spectral variation can be attributed to the difference in the degree of quenching the internal motion and/or the structural heterogeneity caused by molecular environment.", "contents": "An interpretation of the three line EPR spectrum of nitric oxide hemeproteins and related model systems: the effect of the heme environment. The EPR spectra of the nitric oxide (NO) derivatives of structurally perturbed Fe (II) hemeproteins show various patterns, all of which are characterized by the conspicuous three-line hyperfine splitting due to 14NO, in contrast to that of the native proteins. For the purpose of obtaining structural information from these three line spectra, the model systems were studied, which consist of NO, heme (or TPP-Fe(II), where TTP means alpha, beta, gamma, delta-tetraphenylporphine) and the nitrogenous base, pyridine or quinoline, which, respectively, give the native type or the three line (perturbed type) EPR spectrum. The ring proton paramagnetic shift of quinoline in this system shows that it is not coordinated to NO-TPP-Fe(II) as a normal axial ligand, in contrast to pyridine which gives the shift pattern of the ordinary axial ligation. This observation suggests that in the NO-hemeproteins some perturbations of the protein structure cause the rupture or distortion of the bond between the imidazole nitrogen on the fifth coordination site and the heme iron, resulting in the three line spectrum. The EPR study of the model systems, the pentacoordinated complex, NO-heme and NO-TPP-Fe(II), in various media revealed that the pentacoordinated species indeed exhibits, depending upon its environment, a variety of spectra, which closely reproduce the three line patterns observed in the perturbed proteins and some related model systems. Such spectral variation can be attributed to the difference in the degree of quenching the internal motion and/or the structural heterogeneity caused by molecular environment."} {"id": "PMID:164908", "title": "An extended Scatchard analysis for competitively bound ligands and its application to cyclic adenosine-3',5'-monophosphate and cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate binding to beef skeletal muscle protein.", "content": "A method for determining the dissociation constants of ligands and ligand analogs is described. It is based on competition binding studies in the presence of an isotope-labeled, or otherwise measurable, ligand and suitable analog concentrations. The steps used are determination of (1) the maximal amount of radioactive ligand that can be bound, (2) the slopes and intercepts from Scatchard plots at different analog concentrations and (3) the values for the dissociation constants of radioactive ligand and ligand analog from replots of the reciprocals of the slopes and intercepts obtained from the Scatchard plots. Application of the method to a cyclic AMP-binding protein from beef muscle is demonstrated, yielding dissociation constants of 2.10-9 M for cyclic (3H) AMP and cyclic AMP, and 3.10-5 M for cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate.", "contents": "An extended Scatchard analysis for competitively bound ligands and its application to cyclic adenosine-3',5'-monophosphate and cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate binding to beef skeletal muscle protein. A method for determining the dissociation constants of ligands and ligand analogs is described. It is based on competition binding studies in the presence of an isotope-labeled, or otherwise measurable, ligand and suitable analog concentrations. The steps used are determination of (1) the maximal amount of radioactive ligand that can be bound, (2) the slopes and intercepts from Scatchard plots at different analog concentrations and (3) the values for the dissociation constants of radioactive ligand and ligand analog from replots of the reciprocals of the slopes and intercepts obtained from the Scatchard plots. Application of the method to a cyclic AMP-binding protein from beef muscle is demonstrated, yielding dissociation constants of 2.10-9 M for cyclic (3H) AMP and cyclic AMP, and 3.10-5 M for cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate."} {"id": "PMID:164909", "title": "Hormone action at the membrane level. IV. Epinephrine binding to rat liver plasma membranes and rat epididymal fat cells.", "content": "[3-H]Epinephrine binding to isolated purified rat liver plasma membranes is a reversible process. An initial peak in binding occurs at about 15 min and a plateau occurs by 50 min. Optimal binding occurred at a membrane protein concentration of 125mug. Rat liver plasma membranes stored at-70 degrees C up to 4 weeks showed no difference in epinephrine binding capacity as compared to control fresh membranes. Epinephrine binding to liver plasma membranes was decreased by 79% by phospholipase A2 (phosphatide acylhydrolase EC 3.1.1.4), 81% by phospholipase C (phosphatidylcholine choline phosphohydrolase EC 3.1.4.3) and 59% by phospholipase D (phosphatidylcholine phosphatidohydrolase EC 3.1.4.4). Trypsin and pronase digestion of the membrane decreased epinephrine binding by 97 and 47% respectively. In the presence of 10-3M Mg-2+ ions, increasing concentrations of QTP decreased epinephrine binding to liver plasma membranes. A maximal effect was demonstrated with 10-5M GTP, representing an inhibition of 52% of the control. In a Mg-2+ -free system, epinephrine binding was unaffected by GTP. However, in a Mg-2+ -free system, increasing concentrations of ATP cause increasing inhibition of hormone binding. ATP at 10-3 M reduced epinephrine binding to 28% of the control. GRP (10-5 M) was shown to inhibit epinephrine uptake rather than epinephrine release from the membrane. [3-H]Epinephrine binding to isolated rat epididymal fat cells shows an initial peak within 5 min followed by a gradual rise which plateaus after 60 min. Epinephrine binding increased nearly linearly with increasing fat cell protein concentration (40-200 mug protein). GTP (10-5 M) and ATP (10-4 M) decreased epinephrine binding to rat epididymal fat cells by 41%. Nearly complete inhibition of binding was demonstrated with 10-2-10-3M ATP. Epinephrine analogs that contain two hydroxyl groups in the 3 and 4 position on the benzene ring act as inhibitors of [3-H]epinephrine binding to rat adipocytes. Alteration of the epinephrine side chain has relatively little influence on binding. Analogs in which one of the ring hydroxyl groups is missing or methylated are poor inhibitors of [3-H]epinephrine binding. Alpha-(phentolamine and phenoxybenzamine) and beta-(propranolol and dichorisoproterenol) adrenergic blocking agents were tested with respect to their ability to influence [3-H]epinephrine binding and their influence on epinephrine-stimulated lipolysis. Only dichloroisoproterenol significantly inhibited epinephrine binding (by 25%). The two beta-adrenergic blocking agents caused an inhibition of epinephrine-stimulated glycerol release, with propranolol being most effective. Phentolamine and phenoxybenzamine had no significant effect on the epinephrine stimulation of glycerol release by fat cells.", "contents": "Hormone action at the membrane level. IV. Epinephrine binding to rat liver plasma membranes and rat epididymal fat cells. [3-H]Epinephrine binding to isolated purified rat liver plasma membranes is a reversible process. An initial peak in binding occurs at about 15 min and a plateau occurs by 50 min. Optimal binding occurred at a membrane protein concentration of 125mug. Rat liver plasma membranes stored at-70 degrees C up to 4 weeks showed no difference in epinephrine binding capacity as compared to control fresh membranes. Epinephrine binding to liver plasma membranes was decreased by 79% by phospholipase A2 (phosphatide acylhydrolase EC 3.1.1.4), 81% by phospholipase C (phosphatidylcholine choline phosphohydrolase EC 3.1.4.3) and 59% by phospholipase D (phosphatidylcholine phosphatidohydrolase EC 3.1.4.4). Trypsin and pronase digestion of the membrane decreased epinephrine binding by 97 and 47% respectively. In the presence of 10-3M Mg-2+ ions, increasing concentrations of QTP decreased epinephrine binding to liver plasma membranes. A maximal effect was demonstrated with 10-5M GTP, representing an inhibition of 52% of the control. In a Mg-2+ -free system, epinephrine binding was unaffected by GTP. However, in a Mg-2+ -free system, increasing concentrations of ATP cause increasing inhibition of hormone binding. ATP at 10-3 M reduced epinephrine binding to 28% of the control. GRP (10-5 M) was shown to inhibit epinephrine uptake rather than epinephrine release from the membrane. [3-H]Epinephrine binding to isolated rat epididymal fat cells shows an initial peak within 5 min followed by a gradual rise which plateaus after 60 min. Epinephrine binding increased nearly linearly with increasing fat cell protein concentration (40-200 mug protein). GTP (10-5 M) and ATP (10-4 M) decreased epinephrine binding to rat epididymal fat cells by 41%. Nearly complete inhibition of binding was demonstrated with 10-2-10-3M ATP. Epinephrine analogs that contain two hydroxyl groups in the 3 and 4 position on the benzene ring act as inhibitors of [3-H]epinephrine binding to rat adipocytes. Alteration of the epinephrine side chain has relatively little influence on binding. Analogs in which one of the ring hydroxyl groups is missing or methylated are poor inhibitors of [3-H]epinephrine binding. Alpha-(phentolamine and phenoxybenzamine) and beta-(propranolol and dichorisoproterenol) adrenergic blocking agents were tested with respect to their ability to influence [3-H]epinephrine binding and their influence on epinephrine-stimulated lipolysis. Only dichloroisoproterenol significantly inhibited epinephrine binding (by 25%). The two beta-adrenergic blocking agents caused an inhibition of epinephrine-stimulated glycerol release, with propranolol being most effective. Phentolamine and phenoxybenzamine had no significant effect on the epinephrine stimulation of glycerol release by fat cells."} {"id": "PMID:164910", "title": "Sodium + potassium-activated ATPase of mammalian brain. Regulation of phosphatase activity.", "content": "1. The K+-nitrophenylphosphatase activity associated with mammalian brain (Na+ + K+)-ATPase displays K+ activation curves that have intermediary plateaus and maxima in the presence of less than saturating concentrations of Na+. Zero Na+ and saturating Na+ produce sigmoid K+-activation curves with low and high K+ affinities respectively. 2. ATP inhibits K+-activated nitrophenylphosphatase through both competitive and non-competitive mechanisms. ATP is synergistic with Na+ in the mechanism which converts the enzyme from low to high K+ affinity. 3. The Na+ and K+ interactions can be accounted for by equations which describe a model with separate regulatory sites for Na+ and K+ and with K+- requiring catalytic site which is only accessible in one of the two principal conformational stages of the enzyme. 4. The effects of ATP can be accounted for by the same model through interactions at a single nucleotide binding site. Inhibition which is competitive with K+ and non-competitive with substrate arises from stabilization of the inactive enzyme conformation. Inhibition which is non-competitive with K+ and competitive with substrate results from interactions with the active enzyme conformation. The synergism between Na+ and ATP appears to arise as a consequence of the formation of phosphoryl enzyme. 5. A model for (Na+ + K+)-ATPase is discussed which involves in-phase coupling of subunit interactions as suggested by these studies.", "contents": "Sodium + potassium-activated ATPase of mammalian brain. Regulation of phosphatase activity. 1. The K+-nitrophenylphosphatase activity associated with mammalian brain (Na+ + K+)-ATPase displays K+ activation curves that have intermediary plateaus and maxima in the presence of less than saturating concentrations of Na+. Zero Na+ and saturating Na+ produce sigmoid K+-activation curves with low and high K+ affinities respectively. 2. ATP inhibits K+-activated nitrophenylphosphatase through both competitive and non-competitive mechanisms. ATP is synergistic with Na+ in the mechanism which converts the enzyme from low to high K+ affinity. 3. The Na+ and K+ interactions can be accounted for by equations which describe a model with separate regulatory sites for Na+ and K+ and with K+- requiring catalytic site which is only accessible in one of the two principal conformational stages of the enzyme. 4. The effects of ATP can be accounted for by the same model through interactions at a single nucleotide binding site. Inhibition which is competitive with K+ and non-competitive with substrate arises from stabilization of the inactive enzyme conformation. Inhibition which is non-competitive with K+ and competitive with substrate results from interactions with the active enzyme conformation. The synergism between Na+ and ATP appears to arise as a consequence of the formation of phosphoryl enzyme. 5. A model for (Na+ + K+)-ATPase is discussed which involves in-phase coupling of subunit interactions as suggested by these studies."} {"id": "PMID:164911", "title": "Interaction of Clostridium perfringens theta-haemolysin, a contaminant of commercial phospholipase C, with erythrocyte ghost membranes and lipid dispersions. A morphological study.", "content": "Commercially available preparations of phospholipase C from Clostridium perfringens are commonly contaminated with theta haemolysin, one of a group of bacterial haemolysins called oxygen labile (O-labile) haemolysins. Treatment of erythrocyte ghosts and a mixed lipid dispersion containing cholesterol with commercially available phospholipase C in the absence of Ca-2+ and the presence of phosphate buffer and/or EDTA resulted in the formation and release of ring or arc-shaped structures. Highly purified phospholipase C, free of theta-haemolysin, produced no changes in the morphology of erythrocyte ghosts or lipid dispersions in the presence of phosphate or EDTA, but caused the formation of typical diglyceride droplets in the presence of Ca-2+ in the absence of these inhibitors. Ring structures, identical to those caused by commercial phospholipase C, were formed on addition of highly purified theta-haemolysin to erythrocyte ghost membranes, lipid dispersions containing cholesterol and cholesterol dispersions, but not on treatment of membranes from Micrococcus lysodeikticus. Heat-inactivated O-haemolysin (60 degrees C for 10 min) produced no such effects. The dimensions of rings and arcs displayed heterogeneity. The outside diameters in various preparations varied from approx. 27-58 nm with border thickness of 4.1-7.8 nm.", "contents": "Interaction of Clostridium perfringens theta-haemolysin, a contaminant of commercial phospholipase C, with erythrocyte ghost membranes and lipid dispersions. A morphological study. Commercially available preparations of phospholipase C from Clostridium perfringens are commonly contaminated with theta haemolysin, one of a group of bacterial haemolysins called oxygen labile (O-labile) haemolysins. Treatment of erythrocyte ghosts and a mixed lipid dispersion containing cholesterol with commercially available phospholipase C in the absence of Ca-2+ and the presence of phosphate buffer and/or EDTA resulted in the formation and release of ring or arc-shaped structures. Highly purified phospholipase C, free of theta-haemolysin, produced no changes in the morphology of erythrocyte ghosts or lipid dispersions in the presence of phosphate or EDTA, but caused the formation of typical diglyceride droplets in the presence of Ca-2+ in the absence of these inhibitors. Ring structures, identical to those caused by commercial phospholipase C, were formed on addition of highly purified theta-haemolysin to erythrocyte ghost membranes, lipid dispersions containing cholesterol and cholesterol dispersions, but not on treatment of membranes from Micrococcus lysodeikticus. Heat-inactivated O-haemolysin (60 degrees C for 10 min) produced no such effects. The dimensions of rings and arcs displayed heterogeneity. The outside diameters in various preparations varied from approx. 27-58 nm with border thickness of 4.1-7.8 nm."} {"id": "PMID:164912", "title": "An EPR study of structural perturbations induced by methylindole in the protein and lipid regions of erythrocyte membranes.", "content": "3-Methylindole has been shown in previous work to cause pulmonary edema and emphysema in cattle and goats. In this paper, evidence is presented to show that 3-methylindole induces structural perturbations in bovine erythrocyte membranes. The structural perturbations which were induced as a function of 3-methylindole concentration in the membranes were measured by EPR using the attachment of maleimide spin label to the sulfhydryl groups of membrane proteins and by intercalation of methyl-5- doxylstearate, methyl-12-doxylstearate, and methyl-16-doxylstearate into the lipid region. The EPR spectra of the malemide spin-labeled membrane proteins became more immobilized as the concentration of 3-methyl-indole increased. The order parameter describing the EPR spectra of methyl-5-doxylstearate decreased from 0.69 to 0.55 as the concentration of 3-methylindole increased. The acyl chains in the region of the carbon 5 position were converted to a less ordered structure. The EPR-spectra of methyl-12-doxylstearate was a superposition representing at least three tumbling rates. As the concentration of 3-methylindole increased, the major fraction of the methyl-12-doxylstearate probes experienced an increase in tumbling rate and a smaller fraction is observed a strongly immobilized state. The EPR spectra of methyl-16-doxylstearate were not perceptibly changed in the presence of 3-methylindole. The concentration dependence suggests that 3-methylindole preferentially intercalates into the ordered region of the alkyl chains sampled by the methyl-5-doxylstearate. These results confirm that 3-methylindole induced structural changes at the molecular level.", "contents": "An EPR study of structural perturbations induced by methylindole in the protein and lipid regions of erythrocyte membranes. 3-Methylindole has been shown in previous work to cause pulmonary edema and emphysema in cattle and goats. In this paper, evidence is presented to show that 3-methylindole induces structural perturbations in bovine erythrocyte membranes. The structural perturbations which were induced as a function of 3-methylindole concentration in the membranes were measured by EPR using the attachment of maleimide spin label to the sulfhydryl groups of membrane proteins and by intercalation of methyl-5- doxylstearate, methyl-12-doxylstearate, and methyl-16-doxylstearate into the lipid region. The EPR spectra of the malemide spin-labeled membrane proteins became more immobilized as the concentration of 3-methyl-indole increased. The order parameter describing the EPR spectra of methyl-5-doxylstearate decreased from 0.69 to 0.55 as the concentration of 3-methylindole increased. The acyl chains in the region of the carbon 5 position were converted to a less ordered structure. The EPR-spectra of methyl-12-doxylstearate was a superposition representing at least three tumbling rates. As the concentration of 3-methylindole increased, the major fraction of the methyl-12-doxylstearate probes experienced an increase in tumbling rate and a smaller fraction is observed a strongly immobilized state. The EPR spectra of methyl-16-doxylstearate were not perceptibly changed in the presence of 3-methylindole. The concentration dependence suggests that 3-methylindole preferentially intercalates into the ordered region of the alkyl chains sampled by the methyl-5-doxylstearate. These results confirm that 3-methylindole induced structural changes at the molecular level."} {"id": "PMID:164913", "title": "Cellular binding sites for insulin in rat liver.", "content": "A study of the sites of insulin binding in subcellular fractions of rat liver is reported. A method for the isolation of liver plasma membranes, which permits one to follow quantitatively the distribution of all the parameters of interest, was modified and applied to the study of the cellular topography of insulin binding. The insulin binding capacity did not follow closely the enzyme marker (5'-nucleotidase) for plasma membranes when differential centrifugation schemes were used, and the divergence from this marker was more prominent when separations were performed on discontinous sucrose gradients. A significant amount of insulin binding capacity was always present in fractions with higher density than those containing the majority of 5'-nycleotidase. Results of studies on linear sucrose gradients have disclosed in some of the purified membrane fractions small but consistent differences in density of the insulin binding, and plasma membrane particles. It is suggested that there may be several types of intracellular membranes to which insulin can bind besides the plasma membranes.", "contents": "Cellular binding sites for insulin in rat liver. A study of the sites of insulin binding in subcellular fractions of rat liver is reported. A method for the isolation of liver plasma membranes, which permits one to follow quantitatively the distribution of all the parameters of interest, was modified and applied to the study of the cellular topography of insulin binding. The insulin binding capacity did not follow closely the enzyme marker (5'-nucleotidase) for plasma membranes when differential centrifugation schemes were used, and the divergence from this marker was more prominent when separations were performed on discontinous sucrose gradients. A significant amount of insulin binding capacity was always present in fractions with higher density than those containing the majority of 5'-nycleotidase. Results of studies on linear sucrose gradients have disclosed in some of the purified membrane fractions small but consistent differences in density of the insulin binding, and plasma membrane particles. It is suggested that there may be several types of intracellular membranes to which insulin can bind besides the plasma membranes."} {"id": "PMID:164914", "title": "Cyclic adenosine monophosphate receptor: effect of cyclic AMP analogues on DNA binding and proteolytic inactivation.", "content": "The cyclic AMP receptor protein of Escherichia coli in the presence of cyclic AMP undergoes a conformational change resulting in an increased affinity for DNA and an increased susceptibility to attack by proteolytic enzymes resulting in loss of DNA binding capacity. Of several cyclic nucleotides tested only cyclic AMP and cyclic tubercidin monophosphate are able to effect the conformational transition in cyclic AMP receptor protein, prerequisite to proteolytic inactivation or DNA binding. Other analogues such as cyclic GMP or cyclic IMP which are competitive inhibitors of cyclic AMP do not support DNA binding or proteolytic inactivation.", "contents": "Cyclic adenosine monophosphate receptor: effect of cyclic AMP analogues on DNA binding and proteolytic inactivation. The cyclic AMP receptor protein of Escherichia coli in the presence of cyclic AMP undergoes a conformational change resulting in an increased affinity for DNA and an increased susceptibility to attack by proteolytic enzymes resulting in loss of DNA binding capacity. Of several cyclic nucleotides tested only cyclic AMP and cyclic tubercidin monophosphate are able to effect the conformational transition in cyclic AMP receptor protein, prerequisite to proteolytic inactivation or DNA binding. Other analogues such as cyclic GMP or cyclic IMP which are competitive inhibitors of cyclic AMP do not support DNA binding or proteolytic inactivation."} {"id": "PMID:164915", "title": "Depression by NAD of x-ray-induced repair-type DNA synthesis in toluene-treated Bacillus subtilis.", "content": "NAD prevents a DNA repair-type synthesis that is dependent on polymerase I in toluene-treated, X-irradiated Bacillus subtilis. In unirradiated preparations, NAD had little effect on an ATP-dependent, semiconservative synthesis but partially inhibited a repair-type synthesis. In a mutant lacking polymerase I (polA1-), the presence of NAD did not affect dTTP utilization in DNA synthesis. Nicotinamide mononucleotide (NMN) partially reverses the NAD inhibition of repair-type DNA synthesis. NADP and FAD were ineffective as substitutes for NAD. Since NAD is the cofactor for polynucleotide ligase in Bacillus subtilis and NMN is known to discharge AMP from the active AMP ligase complex, it is proposed that activation of DNA ligase reduces dTMP incorporation by reducing sites for, or limiting DNA polymerase I action.", "contents": "Depression by NAD of x-ray-induced repair-type DNA synthesis in toluene-treated Bacillus subtilis. NAD prevents a DNA repair-type synthesis that is dependent on polymerase I in toluene-treated, X-irradiated Bacillus subtilis. In unirradiated preparations, NAD had little effect on an ATP-dependent, semiconservative synthesis but partially inhibited a repair-type synthesis. In a mutant lacking polymerase I (polA1-), the presence of NAD did not affect dTTP utilization in DNA synthesis. Nicotinamide mononucleotide (NMN) partially reverses the NAD inhibition of repair-type DNA synthesis. NADP and FAD were ineffective as substitutes for NAD. Since NAD is the cofactor for polynucleotide ligase in Bacillus subtilis and NMN is known to discharge AMP from the active AMP ligase complex, it is proposed that activation of DNA ligase reduces dTMP incorporation by reducing sites for, or limiting DNA polymerase I action."} {"id": "PMID:164916", "title": "On the role of tryptophan residues in the mechanism of action of glyceraldehyde-3phosphate dehydrogenase as tested by specific modification.", "content": "A method is described to selectively modify one of the three tryptophan residues of the subunit of glyceraldehyde-3-phosphate dehydrogenase from yeast. As modifying agent dimethyl (2-hydroxy-5-nitrobenzyl) sulfonium bromide was used. The residue which is modified by the procedure described has been identified as Trp-193. There are either one or two molecules of the modifying agent being added to this tryptophan side chain. The modification apparently does not cause a detectable conformational change of the protein as judged from the methods employed. However, the enzymatic activities in the dehydrogenase as well as in the esterase reactions are lost after the modification. It could be established that the modification rendered the enzyme unable to bind the oxidized coenzyme. Also the charge-transfer interaction between enzyme and coenzyme could no longer be observed.", "contents": "On the role of tryptophan residues in the mechanism of action of glyceraldehyde-3phosphate dehydrogenase as tested by specific modification. A method is described to selectively modify one of the three tryptophan residues of the subunit of glyceraldehyde-3-phosphate dehydrogenase from yeast. As modifying agent dimethyl (2-hydroxy-5-nitrobenzyl) sulfonium bromide was used. The residue which is modified by the procedure described has been identified as Trp-193. There are either one or two molecules of the modifying agent being added to this tryptophan side chain. The modification apparently does not cause a detectable conformational change of the protein as judged from the methods employed. However, the enzymatic activities in the dehydrogenase as well as in the esterase reactions are lost after the modification. It could be established that the modification rendered the enzyme unable to bind the oxidized coenzyme. Also the charge-transfer interaction between enzyme and coenzyme could no longer be observed."} {"id": "PMID:164917", "title": "Changes in cyclic AMP-dependent protein dinase activity in Tetrahymena pyriformis during the growth cycle.", "content": "An adenosine 3':5'-monophosphate-dependent protein kinase II (ATP:protein phosphotransferase, EC 2.7.1.37) was partially purified from the cytosol fraction of an exponentially growing culture of Tetrahymena pyriformis. Protein kinase II represented approximately 90% of the cytosolic protein kinase activity. The enzyme had a high degree of substrate specificity for calf thymus and Tetrahymena histones as compared to casein, protamine and phosvitin. The enzyme incorporated the terminal phosphate of ATP into serine and threonine residues of all the histone fractions. The apparent Km of the enzyme for adenosine 3':5'-monophosphate (cyclic AMP) was 1-10-minus 8 M. Protein kinase II was also activated by other cyclic nucleotides with apparent Km values in the range 2.k-10-minus 6 M. Ther specific activity of the cyclic AMP-dependent protein kinase of Tetrahymena decreases markedly from initial high values during the transition from the lag to early log phase of growth. This is followed by a shrp increase in the activity of the enzyme as the log phase of growth progresses. The specific activity of the enzyme increases rapidly during the heat-induced synchronization of Tetrahymena cells. The capacity for rapid phosphorylation of multiple classed of organelle-specific phosphoproteins and the level of cyclic AMP were maximal in Tetrahymena during the earliest phase of growth. These results demonstrate that the cell cycle of Tetrahymena may be coordinated by marked variations in the level of cyclic AMP which in turn regulate the cyclic AMP-dependent protein kinase.", "contents": "Changes in cyclic AMP-dependent protein dinase activity in Tetrahymena pyriformis during the growth cycle. An adenosine 3':5'-monophosphate-dependent protein kinase II (ATP:protein phosphotransferase, EC 2.7.1.37) was partially purified from the cytosol fraction of an exponentially growing culture of Tetrahymena pyriformis. Protein kinase II represented approximately 90% of the cytosolic protein kinase activity. The enzyme had a high degree of substrate specificity for calf thymus and Tetrahymena histones as compared to casein, protamine and phosvitin. The enzyme incorporated the terminal phosphate of ATP into serine and threonine residues of all the histone fractions. The apparent Km of the enzyme for adenosine 3':5'-monophosphate (cyclic AMP) was 1-10-minus 8 M. Protein kinase II was also activated by other cyclic nucleotides with apparent Km values in the range 2.k-10-minus 6 M. Ther specific activity of the cyclic AMP-dependent protein kinase of Tetrahymena decreases markedly from initial high values during the transition from the lag to early log phase of growth. This is followed by a shrp increase in the activity of the enzyme as the log phase of growth progresses. The specific activity of the enzyme increases rapidly during the heat-induced synchronization of Tetrahymena cells. The capacity for rapid phosphorylation of multiple classed of organelle-specific phosphoproteins and the level of cyclic AMP were maximal in Tetrahymena during the earliest phase of growth. These results demonstrate that the cell cycle of Tetrahymena may be coordinated by marked variations in the level of cyclic AMP which in turn regulate the cyclic AMP-dependent protein kinase."} {"id": "PMID:164918", "title": "Investigation of the adenosine 3', 5'-cyclic phosphate binding site of pig brain histone kinase with the aid of some analogues of adenosine 3', 5'-cyclic phosphate.", "content": "2'-O-Chloroacetyl cyclic AMP, 2'-O-acrylyl cyclic AMP and N-6, 2'-O-diacrylyl cyclic AMP were synthesized by the reaction of cyclic AMP with chloroacetic and acrylic anhydrides, respectively. Selective O-deacylation of N-6, 2'-O-diacrylyl cyclic AMP yielded N-6 -monoacrylyl cyclic AMP. In the reaction of gamma-mercaptobutyric acid with 8-bromo cyclic AMP, 8-(gamma-carboxypropylthio) cyclic AMP was obtained. The compounds synthesized and other cyclic AMP analogues (8-bromo cyclic AMP and adenosine 3', 5'-cyclic sulphate) were tested for ability to interact with the highly purified pig brain histone kinase. All compounds under study were found to be activators of the enzyme. The highest activating potency was manifested by 8-bromo cyclic AMP and 8-(gamma-carboxypropylthio) cyclic AMP; adenosine 3', 5'-cyclic sulphate was the least potent in this respect. All compounds were shown to inhibit binding of cyclic [-3-H]AMP to histone kinase. The inhibition was competitive with respect to cyclic AMP in all cases. All compounds, except for 2'-O-chloroacetyl cyclic AMP may indicate the formation of a covalent bond between this analogue and the enzyme. These findings suggest that an active site of the regulatory subunit of the histone kinase contains at least three specific areas responsible for cyclic AMP binding.", "contents": "Investigation of the adenosine 3', 5'-cyclic phosphate binding site of pig brain histone kinase with the aid of some analogues of adenosine 3', 5'-cyclic phosphate. 2'-O-Chloroacetyl cyclic AMP, 2'-O-acrylyl cyclic AMP and N-6, 2'-O-diacrylyl cyclic AMP were synthesized by the reaction of cyclic AMP with chloroacetic and acrylic anhydrides, respectively. Selective O-deacylation of N-6, 2'-O-diacrylyl cyclic AMP yielded N-6 -monoacrylyl cyclic AMP. In the reaction of gamma-mercaptobutyric acid with 8-bromo cyclic AMP, 8-(gamma-carboxypropylthio) cyclic AMP was obtained. The compounds synthesized and other cyclic AMP analogues (8-bromo cyclic AMP and adenosine 3', 5'-cyclic sulphate) were tested for ability to interact with the highly purified pig brain histone kinase. All compounds under study were found to be activators of the enzyme. The highest activating potency was manifested by 8-bromo cyclic AMP and 8-(gamma-carboxypropylthio) cyclic AMP; adenosine 3', 5'-cyclic sulphate was the least potent in this respect. All compounds were shown to inhibit binding of cyclic [-3-H]AMP to histone kinase. The inhibition was competitive with respect to cyclic AMP in all cases. All compounds, except for 2'-O-chloroacetyl cyclic AMP may indicate the formation of a covalent bond between this analogue and the enzyme. These findings suggest that an active site of the regulatory subunit of the histone kinase contains at least three specific areas responsible for cyclic AMP binding."} {"id": "PMID:164919", "title": "Cyclic nucleotide phosphodiesterase activities of pig coronary arteries.", "content": "Most (85% or more) of the cyclic nucleotide phosphodiesterase (3' :5' -cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) activity of pig coronary arteries was found in the 40 000 times g supernatant fraction of homogenates of the intima plus media layer. Chromatography of the soluble fraction of this layer on DEAE-cellulose resolved two phosphodiesterase activities and a heat stable, non-dializable activator. Peak I activity had apparent Km values of 2-4 muM for cyclic GMP and 40-100 muM for cyclic AMP. Peak II activity was relatively specific for cyclic AMP and exhibited apparent negatively cooperative behavior. Peak I but not peak II activity could be stimulated 3-8-fold by the addition of the boiled activator fraction or a boiled crude supernatant fraction. Cyclic AMP hydrolysis by peak I or peak II was more rapid in the presence of Mn-2+ than Mg-2+, but the latter promoted hydrolysis of cyclic GMP by peak I more effectively than did Mn-2+ in the presence of activator. In the absence of added metals, ethylene bis(oxyethylenenitriol)tetra-acetic acid (EGTA) and EDTA both inhibited hydrolysis of cyclic AMP and cyclic GMP by phosphodiesterase activities in the supernatant fraction and in peak I, but EDTA produced more complete inhibition at lower concentrations than did EGTA. Imidazole (1 muM to 10 mM) had virtually no effect on the hydrolysis of cyclic AMP or cyclic GMP catalyzed by either of the two separated peaks or by total phosphodiesterase activities in crude supernatant or particulate fractions.", "contents": "Cyclic nucleotide phosphodiesterase activities of pig coronary arteries. Most (85% or more) of the cyclic nucleotide phosphodiesterase (3' :5' -cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) activity of pig coronary arteries was found in the 40 000 times g supernatant fraction of homogenates of the intima plus media layer. Chromatography of the soluble fraction of this layer on DEAE-cellulose resolved two phosphodiesterase activities and a heat stable, non-dializable activator. Peak I activity had apparent Km values of 2-4 muM for cyclic GMP and 40-100 muM for cyclic AMP. Peak II activity was relatively specific for cyclic AMP and exhibited apparent negatively cooperative behavior. Peak I but not peak II activity could be stimulated 3-8-fold by the addition of the boiled activator fraction or a boiled crude supernatant fraction. Cyclic AMP hydrolysis by peak I or peak II was more rapid in the presence of Mn-2+ than Mg-2+, but the latter promoted hydrolysis of cyclic GMP by peak I more effectively than did Mn-2+ in the presence of activator. In the absence of added metals, ethylene bis(oxyethylenenitriol)tetra-acetic acid (EGTA) and EDTA both inhibited hydrolysis of cyclic AMP and cyclic GMP by phosphodiesterase activities in the supernatant fraction and in peak I, but EDTA produced more complete inhibition at lower concentrations than did EGTA. Imidazole (1 muM to 10 mM) had virtually no effect on the hydrolysis of cyclic AMP or cyclic GMP catalyzed by either of the two separated peaks or by total phosphodiesterase activities in crude supernatant or particulate fractions."} {"id": "PMID:164920", "title": "Purification and characteriazation of collagenase from guinea pig skin.", "content": "Guinea pig skin col-agenase, isolated from culture medium of whole skin, was separated into two enzymatically active fractions. These two fractions have been purified extensively. Peak II fraction has been purified to homogeneity as examined by polyacrylamide gel electrophoresis. Their molecular weights are approximately 130 000 (peak I) and 40 000 (peak II). Both guinea pig skin collagenase fractions are capable of degrading the native collagen fibrils and are inhibited by serum, cysteine and EDTA. They appear to be glycoproteins. Guinea pig skin (peak II) and human skin collagenase were compared. They are both glycoproteins and have similar molecular size (Mr = 40 000). Immunodiffusion assay showed that no cross-reactivity was seen between the enzymes, indicating species specificity among collagenases.", "contents": "Purification and characteriazation of collagenase from guinea pig skin. Guinea pig skin col-agenase, isolated from culture medium of whole skin, was separated into two enzymatically active fractions. These two fractions have been purified extensively. Peak II fraction has been purified to homogeneity as examined by polyacrylamide gel electrophoresis. Their molecular weights are approximately 130 000 (peak I) and 40 000 (peak II). Both guinea pig skin collagenase fractions are capable of degrading the native collagen fibrils and are inhibited by serum, cysteine and EDTA. They appear to be glycoproteins. Guinea pig skin (peak II) and human skin collagenase were compared. They are both glycoproteins and have similar molecular size (Mr = 40 000). Immunodiffusion assay showed that no cross-reactivity was seen between the enzymes, indicating species specificity among collagenases."} {"id": "PMID:164921", "title": "Excitation-secretion coupling in exocrine glands. Properties of cyclic AMP phosphodiesterase and adenylate cyclase from the submaxillary gland and pancreas.", "content": "1. The cyclic AMP phosphodiesterase in homogenates of the submaxillary gland and pancreas was found to be associated mainly with the 300,000 times g supernatant fraction. A Lineweaver-Burk plot showed a high-affinity (Km app. = 1.6 muM) and a low-affinity (Km app. greater than 100muM) component for the cyclic AMP substrate. The enzyme was magnesium dependent, and strongly inhibited by papaverine, theophylline and caffeine. Cyclic GMP inhibited cyclic AMP phosphodiesterase, but only in concentrations greatly exceeding that of the cyclic AMP. Calcium did not alter the activity of the enzyme. The activity of the submaxillary cyclic AMP phosphodiesterase was not influenced by noradrenaline, dopamine, histamine, 5-hydroxytryptamine or gamma-amino butyric acid, and that of the pancreatic enzyme by acetylcholine, pancreozymin or secretin. 2. Adenylate cyclases from guinea-pig submaxillary gland and cat pancreas are particulate enzymes. The highest specific activity was recovered from the 1500 times g pellet. Guineo-pig submaxillary adenylate cyclase was activated by fluoride, noradrenaline, isoprenaline and adrenaline. The noradrenaline activation was blocked by the beta-adrenoceptor blocker, propranolol, but not by the alphs-adrenoceptor blocker, phentolamine. Neither acetylcholine nor carbachol had any effect on the adenylate cyclase activity. The apparent Km value for the 10- minus 4 M noradrenaline activated adenylate cyclase activity was completely aboliched by 5 mM calcium. Cat pancreatic adenylate cyclase was clearly and consistently activated by secretin, but not by pancreozymin or carbachol.", "contents": "Excitation-secretion coupling in exocrine glands. Properties of cyclic AMP phosphodiesterase and adenylate cyclase from the submaxillary gland and pancreas. 1. The cyclic AMP phosphodiesterase in homogenates of the submaxillary gland and pancreas was found to be associated mainly with the 300,000 times g supernatant fraction. A Lineweaver-Burk plot showed a high-affinity (Km app. = 1.6 muM) and a low-affinity (Km app. greater than 100muM) component for the cyclic AMP substrate. The enzyme was magnesium dependent, and strongly inhibited by papaverine, theophylline and caffeine. Cyclic GMP inhibited cyclic AMP phosphodiesterase, but only in concentrations greatly exceeding that of the cyclic AMP. Calcium did not alter the activity of the enzyme. The activity of the submaxillary cyclic AMP phosphodiesterase was not influenced by noradrenaline, dopamine, histamine, 5-hydroxytryptamine or gamma-amino butyric acid, and that of the pancreatic enzyme by acetylcholine, pancreozymin or secretin. 2. Adenylate cyclases from guinea-pig submaxillary gland and cat pancreas are particulate enzymes. The highest specific activity was recovered from the 1500 times g pellet. Guineo-pig submaxillary adenylate cyclase was activated by fluoride, noradrenaline, isoprenaline and adrenaline. The noradrenaline activation was blocked by the beta-adrenoceptor blocker, propranolol, but not by the alphs-adrenoceptor blocker, phentolamine. Neither acetylcholine nor carbachol had any effect on the adenylate cyclase activity. The apparent Km value for the 10- minus 4 M noradrenaline activated adenylate cyclase activity was completely aboliched by 5 mM calcium. Cat pancreatic adenylate cyclase was clearly and consistently activated by secretin, but not by pancreozymin or carbachol."} {"id": "PMID:164922", "title": "Protein kinases in brown adipose tissue of developing rats. II. two soluble kinase activities and their affinities for nucleotide and protein substrates.", "content": "A heat-stable, soluble component of brown adipose tissue from newborn rats was found to be readily phosphorylated by protein kinase of the same subcellular fraction. The concentration of this component in brown fat decreased with the age of the animals. A boiled crude microsomal preparation from rat liver was also phosphorylated by brown fat protein kinase. The GTP-linked phosphorylation of the endogenous heat-stable protein was not stimulated by ATP (in contrast to phosphorylation of histone). The maximum velocity of phosphorylation achieved with GTP was about 2.5 times higher than that with ATP as nucleotide substrate. This difference was not due to ATPase activity in the assay. With histone as the protein acceptor both activities were the same. The affinity of protein kinase(s) for ATP was lower with the endogenous heat-stable brown-fat protein and with boiled microsomes (Km of 0.21 mM and 0.17 mM, respectively) than with histone (Km of 0.05 M). No detectable ATPase activity was present in either acceptor protein. It is concluded that the 100 000 times g supernatant fraction from brown fat of infant rats contains two protein kinase activities. One preferentially uses ATP and histone as substrates and the other uses endogenous heat-stable soluble proteins and either ATP or GTP.", "contents": "Protein kinases in brown adipose tissue of developing rats. II. two soluble kinase activities and their affinities for nucleotide and protein substrates. A heat-stable, soluble component of brown adipose tissue from newborn rats was found to be readily phosphorylated by protein kinase of the same subcellular fraction. The concentration of this component in brown fat decreased with the age of the animals. A boiled crude microsomal preparation from rat liver was also phosphorylated by brown fat protein kinase. The GTP-linked phosphorylation of the endogenous heat-stable protein was not stimulated by ATP (in contrast to phosphorylation of histone). The maximum velocity of phosphorylation achieved with GTP was about 2.5 times higher than that with ATP as nucleotide substrate. This difference was not due to ATPase activity in the assay. With histone as the protein acceptor both activities were the same. The affinity of protein kinase(s) for ATP was lower with the endogenous heat-stable brown-fat protein and with boiled microsomes (Km of 0.21 mM and 0.17 mM, respectively) than with histone (Km of 0.05 M). No detectable ATPase activity was present in either acceptor protein. It is concluded that the 100 000 times g supernatant fraction from brown fat of infant rats contains two protein kinase activities. One preferentially uses ATP and histone as substrates and the other uses endogenous heat-stable soluble proteins and either ATP or GTP."} {"id": "PMID:164923", "title": "Location of gluconeogenesis from phosphoenolpyruvate in cotyledons of Cucurbita pepo.", "content": "1. The aim of this work was to discover the location of the enzymes that convert phosphoenolpyruvate to fructose 6-phosphate during gluconeogenesis in fatty seeds. Cotyledons of 5-day-old dark-grown seedlings of marrow (Cucurbita pepo) were used as experimental material. 2. Cotyledons were separated into palisade and mesophyll tissue. Extracts of the two tissues had comparable activities of gluconeogenic enzymes. 3. Extracts of cotyledons were fractionated by density gradient centrifugation to yeild mitochondria and glyoxysomes, and by gel filtration to yield proplastids. The isolated organelles retained their characteristic ultrastructure and appreciable amounts of marker enzymes. The proportions of the total activities of phosphoglyceromutase and fructose-1, 6-diphosphatase recovered in the mitochondrial and glyoxysomal preparations were insignificant. The same was true for the activities of phosphoglyceromutase and phosphopyruvate hydratase found in the proplastid preparations. 4. Extracts of a number of other gluconeigenic plant tissues were centrifuged at 2500 times g to yield particulate preparations. None of these preparations contained a significant proportion of the total activity of phosphoglyceromutase. 5. It is suggested that gluconeogenesis from phosphoenolpyruvate in plants occurs in the cytoplasm.", "contents": "Location of gluconeogenesis from phosphoenolpyruvate in cotyledons of Cucurbita pepo. 1. The aim of this work was to discover the location of the enzymes that convert phosphoenolpyruvate to fructose 6-phosphate during gluconeogenesis in fatty seeds. Cotyledons of 5-day-old dark-grown seedlings of marrow (Cucurbita pepo) were used as experimental material. 2. Cotyledons were separated into palisade and mesophyll tissue. Extracts of the two tissues had comparable activities of gluconeogenic enzymes. 3. Extracts of cotyledons were fractionated by density gradient centrifugation to yeild mitochondria and glyoxysomes, and by gel filtration to yield proplastids. The isolated organelles retained their characteristic ultrastructure and appreciable amounts of marker enzymes. The proportions of the total activities of phosphoglyceromutase and fructose-1, 6-diphosphatase recovered in the mitochondrial and glyoxysomal preparations were insignificant. The same was true for the activities of phosphoglyceromutase and phosphopyruvate hydratase found in the proplastid preparations. 4. Extracts of a number of other gluconeigenic plant tissues were centrifuged at 2500 times g to yield particulate preparations. None of these preparations contained a significant proportion of the total activity of phosphoglyceromutase. 5. It is suggested that gluconeogenesis from phosphoenolpyruvate in plants occurs in the cytoplasm."} {"id": "PMID:164924", "title": "Studies on the interaction between heparin and mouse bone collagenase.", "content": "Mouse bone collagenase was found to be tightly bound to a heparin-substituted gel at low ionic strength. The bond was reversible, however, and the collagenase could be elutted at high ionic strength. In addition to providing a method for purifying the enzyme with high yield, the results suggest that the strong ionic bond between heparin and collagenase may partially explain the mechanism wherein heparin enhances the activity of mouse bone collagenase.", "contents": "Studies on the interaction between heparin and mouse bone collagenase. Mouse bone collagenase was found to be tightly bound to a heparin-substituted gel at low ionic strength. The bond was reversible, however, and the collagenase could be elutted at high ionic strength. In addition to providing a method for purifying the enzyme with high yield, the results suggest that the strong ionic bond between heparin and collagenase may partially explain the mechanism wherein heparin enhances the activity of mouse bone collagenase."} {"id": "PMID:164925", "title": "8-azaguanine and flavinogenesis in Eremothecium ashbyii.", "content": "8-Azaguanine (10- minus 4 M) supplementation in synthetic medium inhibited flavinogenesis in Eremothecium ashbyii to far greater extent (68per cent) than the growth (25 per cent). That enzymes comprising the biosynthetic pathway of riboflavin are synthesized during early growth phase of the organism is supported by the data presented. 8-Azaguanine mediated inhibition in flavinogenesis was closely related with decreased levels of ribose-5'-phosphatase, ribose reductase and ribitol kinase, the enzymes involved in supplying ribitol for flavinogenesis. Addition of guanine and not ribitol during early growth phase to 8-azaguanine-added cultures released the inhibition of riboflavin synthesis and restored the enzyme levels in the presence of the antimetabolite.", "contents": "8-azaguanine and flavinogenesis in Eremothecium ashbyii. 8-Azaguanine (10- minus 4 M) supplementation in synthetic medium inhibited flavinogenesis in Eremothecium ashbyii to far greater extent (68per cent) than the growth (25 per cent). That enzymes comprising the biosynthetic pathway of riboflavin are synthesized during early growth phase of the organism is supported by the data presented. 8-Azaguanine mediated inhibition in flavinogenesis was closely related with decreased levels of ribose-5'-phosphatase, ribose reductase and ribitol kinase, the enzymes involved in supplying ribitol for flavinogenesis. Addition of guanine and not ribitol during early growth phase to 8-azaguanine-added cultures released the inhibition of riboflavin synthesis and restored the enzyme levels in the presence of the antimetabolite."} {"id": "PMID:164926", "title": "Stimulatory effect of gonadotropins on the synthesis of adenosine 3': 5'-cyclic monophosphate and progesterone by suspensions of rat ovarian interstitial cells.", "content": "A cell suspension was prepared from immature rat ovaries by treatment with trypsin and collagenase. The isolated cells were capable of converting [8-14-C]adenine to cyclic [-14-C]AMP and the rate of this conversion was stimulated in vitro by luteinizing hormone and human chorionic gonadotropine, but not by prolactin, norepinephrine, dopamine or albumin. The accumulation of progesterone was also measured in these cells by radioimmunoassay. In vitro addition of luteinizing hormone and human chorionic gonadotropine, but not by prolactin, norepinephrine, dopamine or albumin. The accumulation of progesterone was also measured in these cells by radioimmunoassay. In vitro addition of luteinizing hormone stimulated the accumulation of radioimmuno-assayable progesterone. The conversion of [8-14-C]adenine to cyclic [-14-C]AMP showed a rapid increase during the first 30 min of the incubation period when luteinizing hormone was added to the incubation medium. Progesterone accumulation in response to the same dose of luteinizing hormone showed a lag period for the first 30 min of incubation after which there was an increase up to 2 h. The luteinizing hormone-induced progesterone accumulation was sensitive to puromycin, but there was no effect on the luteinizing hormone-induced increase in cyclic [-14-C]AMP formation from [8-14-C]-adenine. Actinomycin D also inhibited the luteinizing hormone-induced progesterone accumulation in rat ovarian interstitial cell suspension is preceded by an increased accumulation of cyclic AMP and that the accumulation of steroid under the influence of luteinizing hormone involve processes sensitive to puromycin and antinomycin D.", "contents": "Stimulatory effect of gonadotropins on the synthesis of adenosine 3': 5'-cyclic monophosphate and progesterone by suspensions of rat ovarian interstitial cells. A cell suspension was prepared from immature rat ovaries by treatment with trypsin and collagenase. The isolated cells were capable of converting [8-14-C]adenine to cyclic [-14-C]AMP and the rate of this conversion was stimulated in vitro by luteinizing hormone and human chorionic gonadotropine, but not by prolactin, norepinephrine, dopamine or albumin. The accumulation of progesterone was also measured in these cells by radioimmunoassay. In vitro addition of luteinizing hormone and human chorionic gonadotropine, but not by prolactin, norepinephrine, dopamine or albumin. The accumulation of progesterone was also measured in these cells by radioimmunoassay. In vitro addition of luteinizing hormone stimulated the accumulation of radioimmuno-assayable progesterone. The conversion of [8-14-C]adenine to cyclic [-14-C]AMP showed a rapid increase during the first 30 min of the incubation period when luteinizing hormone was added to the incubation medium. Progesterone accumulation in response to the same dose of luteinizing hormone showed a lag period for the first 30 min of incubation after which there was an increase up to 2 h. The luteinizing hormone-induced progesterone accumulation was sensitive to puromycin, but there was no effect on the luteinizing hormone-induced increase in cyclic [-14-C]AMP formation from [8-14-C]-adenine. Actinomycin D also inhibited the luteinizing hormone-induced progesterone accumulation in rat ovarian interstitial cell suspension is preceded by an increased accumulation of cyclic AMP and that the accumulation of steroid under the influence of luteinizing hormone involve processes sensitive to puromycin and antinomycin D."} {"id": "PMID:164927", "title": "Chemotaxis and binding of cyclic AMP in cellular slime molds.", "content": "To obtain more information about how cyclic AMP mediates cell aggregation as found in some species of the cellular slime molds, we determined the maximal binding activity of cyclic AMP in different species under various environmental conditions. The binding of cyclic AMP is limited to amoebae using this cyclic nucleotide as chemotactic agent. Maximal binding activity proved to coincide with a maximal chemotactic response and to be related to the length of the period between the vegetative and the aggregative phase. Of the species studied, Dictyostelium discoideum has the highest cellular density of cyclic AMP receptors and is the most sensitive to cyclic AMP as attractant. At 15 degrees C, aggregation begins later, chemotaxis takes effect over a greater distance, and the maximal binding activity is higher than 22 degrees C. The number of cyclic AMP receptors is independent of temperature. The delay in the onset of aggregation and the increased chemotactic response in darkness is not due to a change in the maximal binding activity. The binding of cyclic AMP and its inactivation is discussed in the light of cell aggregation.", "contents": "Chemotaxis and binding of cyclic AMP in cellular slime molds. To obtain more information about how cyclic AMP mediates cell aggregation as found in some species of the cellular slime molds, we determined the maximal binding activity of cyclic AMP in different species under various environmental conditions. The binding of cyclic AMP is limited to amoebae using this cyclic nucleotide as chemotactic agent. Maximal binding activity proved to coincide with a maximal chemotactic response and to be related to the length of the period between the vegetative and the aggregative phase. Of the species studied, Dictyostelium discoideum has the highest cellular density of cyclic AMP receptors and is the most sensitive to cyclic AMP as attractant. At 15 degrees C, aggregation begins later, chemotaxis takes effect over a greater distance, and the maximal binding activity is higher than 22 degrees C. The number of cyclic AMP receptors is independent of temperature. The delay in the onset of aggregation and the increased chemotactic response in darkness is not due to a change in the maximal binding activity. The binding of cyclic AMP and its inactivation is discussed in the light of cell aggregation."} {"id": "PMID:164928", "title": "Regulation of glycogen metabolism in liver by the autonomic nervous system. VI. Possible mechanism of phosphorylase activation by the splanchnic nerve.", "content": "The effects of autonomic-nerve stimulation on the activities of phosphorylase (EC 2.4.1.1), dephospho-phosphorylase kinase (EC 2.7.1.38) and phosphorylase phosphatase (EC 3.1.3.17), and on the concentration of adenosine 3', 5'-monophosphate in rabbit liver were investiaged. Results were compared with the effects of epinephrine and glucagon on these enzymes. 1. The acitivity of liver phosphorylase increased rapidly and markedly on electrical stimulation of the splanchnic nerve, or after intraportal administration of epinephrine or glucagon. The activity was not affected by vagal stimulation. 2. The activity of dephospho-phosphorylase kinase increased about 2--3-fold 1 min after injections of epinephrine and glucagon, glucagon causing more activation than epinephrine. The enzyme activity was not altered by splanchnic-nerve, or vagal stimulation. 3. Injections of epinephrine and glucagon caused marked elevation of liver adenosine 3', 5'-monophosphate within a few minutes. With epinephrine, the nucleotide concentration rose to a maximum after 1 min and amounted to about 3-fold increase, while with glucagon the maximum increase of approximately 8-fold increase was observed after 2 min. Stimulation of the splanchnic nerve for 10 min did not affect the adenosine 3', 5'-monophosphate level in the liver. Vagal stimulation also had no effect on the level. 4. The activity of phosphorylase phosphatase decreased promptly (within 30 s) and markedly on splanchnic-nerve stimulation, but did not change significantly on administration of epinephrine of glucagon. A small but insignificant increase in phosphatase activity wasobserved upon vagal stimulation. 5. The effect of Ca-2+ on purified dephospho-phosphorylase kinase was studied. The activity was found to depend partially on free Ca-2+ at low Ca-2+ concentrations (1-10-minus 7--1-10-minus 5 M). 6. These results suggest that the rise in hepatic phosphorylase content upon splanchnic-nerve stimulation, unlike that induced by epinephrine and glucagon, is not mediated by adenosine 3', 5'-monophosphate and subsequent activation of dephospho-phosphorylase kinase, but rather by inactivation of phosphorylase phosphatase. The possible existence of a new factor in this mechanism is discussed.", "contents": "Regulation of glycogen metabolism in liver by the autonomic nervous system. VI. Possible mechanism of phosphorylase activation by the splanchnic nerve. The effects of autonomic-nerve stimulation on the activities of phosphorylase (EC 2.4.1.1), dephospho-phosphorylase kinase (EC 2.7.1.38) and phosphorylase phosphatase (EC 3.1.3.17), and on the concentration of adenosine 3', 5'-monophosphate in rabbit liver were investiaged. Results were compared with the effects of epinephrine and glucagon on these enzymes. 1. The acitivity of liver phosphorylase increased rapidly and markedly on electrical stimulation of the splanchnic nerve, or after intraportal administration of epinephrine or glucagon. The activity was not affected by vagal stimulation. 2. The activity of dephospho-phosphorylase kinase increased about 2--3-fold 1 min after injections of epinephrine and glucagon, glucagon causing more activation than epinephrine. The enzyme activity was not altered by splanchnic-nerve, or vagal stimulation. 3. Injections of epinephrine and glucagon caused marked elevation of liver adenosine 3', 5'-monophosphate within a few minutes. With epinephrine, the nucleotide concentration rose to a maximum after 1 min and amounted to about 3-fold increase, while with glucagon the maximum increase of approximately 8-fold increase was observed after 2 min. Stimulation of the splanchnic nerve for 10 min did not affect the adenosine 3', 5'-monophosphate level in the liver. Vagal stimulation also had no effect on the level. 4. The activity of phosphorylase phosphatase decreased promptly (within 30 s) and markedly on splanchnic-nerve stimulation, but did not change significantly on administration of epinephrine of glucagon. A small but insignificant increase in phosphatase activity wasobserved upon vagal stimulation. 5. The effect of Ca-2+ on purified dephospho-phosphorylase kinase was studied. The activity was found to depend partially on free Ca-2+ at low Ca-2+ concentrations (1-10-minus 7--1-10-minus 5 M). 6. These results suggest that the rise in hepatic phosphorylase content upon splanchnic-nerve stimulation, unlike that induced by epinephrine and glucagon, is not mediated by adenosine 3', 5'-monophosphate and subsequent activation of dephospho-phosphorylase kinase, but rather by inactivation of phosphorylase phosphatase. The possible existence of a new factor in this mechanism is discussed."} {"id": "PMID:164929", "title": "On the regulation of adenosine 3', 5'-monophosphate synthesis in bacteria. I. Effect of carbon source variation on cyclic AMP synthesis in Escherichia coli B/r.", "content": "1. The effect of carbon source variation in bacterial growth media on their growth rate, inducible enzyme and cyclic AMP synthesis was examined: an inverse relationship between the culture's growth rate and its differential rate of inducible enzyme (tryptophanase and beta-galactosidase), and cyclic AMP synthesis was found. 2. The effect of the culture's growth phase on its sensitivity or resistance to glucose catabolite repression was determined in the wild type and a catabolite insensitive mutant (ABDROI): the wild type's sensitivity to glucose repression was not affected, whereas the insensitivity of the mutant was found to be limited to its early logarithmic phase of growth. At late log, or stationary phase, the mutant was found to be sensitive to glucose repression. 3. Examination of the kinetics of glucose uptake by the mutant, using alpha-[1 4-C] methyl-glucoside showed evidence for two transport systems each with a different affinity to glucose. A low affinity transport system (apparent Km of 3.4-10-minus 5 M) which appears mostly at the early logarithmic phase of growth. A high affinity transport system (apparent Km of 1.2-10-minus 5 M) which appears mostly at the late log and stationary phases of growth. 4. The effect of the culture density variation on its sensitivity to glucose repression showed that sensitivity to glucose catabolic repression is primarily a reflection of the formation of an allosteric effector molecule between glucose and its specific transport molecule which in turn regulates the activity of the adenylate cyclase.", "contents": "On the regulation of adenosine 3', 5'-monophosphate synthesis in bacteria. I. Effect of carbon source variation on cyclic AMP synthesis in Escherichia coli B/r. 1. The effect of carbon source variation in bacterial growth media on their growth rate, inducible enzyme and cyclic AMP synthesis was examined: an inverse relationship between the culture's growth rate and its differential rate of inducible enzyme (tryptophanase and beta-galactosidase), and cyclic AMP synthesis was found. 2. The effect of the culture's growth phase on its sensitivity or resistance to glucose catabolite repression was determined in the wild type and a catabolite insensitive mutant (ABDROI): the wild type's sensitivity to glucose repression was not affected, whereas the insensitivity of the mutant was found to be limited to its early logarithmic phase of growth. At late log, or stationary phase, the mutant was found to be sensitive to glucose repression. 3. Examination of the kinetics of glucose uptake by the mutant, using alpha-[1 4-C] methyl-glucoside showed evidence for two transport systems each with a different affinity to glucose. A low affinity transport system (apparent Km of 3.4-10-minus 5 M) which appears mostly at the early logarithmic phase of growth. A high affinity transport system (apparent Km of 1.2-10-minus 5 M) which appears mostly at the late log and stationary phases of growth. 4. The effect of the culture density variation on its sensitivity to glucose repression showed that sensitivity to glucose catabolic repression is primarily a reflection of the formation of an allosteric effector molecule between glucose and its specific transport molecule which in turn regulates the activity of the adenylate cyclase."} {"id": "PMID:164930", "title": "On the regulation of cyclic AMP level in bacteria. II. In vitro regulation of adenylate cyclase activity. Solubilization and reconstitution of a functional membrane-bound adenylate cyclase system responsive to regulation by glucose.", "content": "1. The in vitro regulation of the membrane bound adenylate cyclase of Escherichia coli B/r by a variety of carbohydrates and one mammalian hormone was examined. 2. The membrane bound adenylate cyclase was found responsive to regulation by the various growth substrates and to glucagon. 3. Solubilization of the bacterial membrane preparation by a procedure specific for the solubilization of the phosphotransferase enzyme E1 1 to its E1 1 A and E1 1 B subunits was found to be accompanied by the loss of the adenylate cyclase regulation by glucose. 4. Reconstitution of the membrane was found to result in a recovery of the regulative response of the adenylate cyclase to glucose. 5. A model for the intermediate steps in the interaction between glucose and phosphotransferase E1 1 and the adenylate cyclase is discussed.", "contents": "On the regulation of cyclic AMP level in bacteria. II. In vitro regulation of adenylate cyclase activity. Solubilization and reconstitution of a functional membrane-bound adenylate cyclase system responsive to regulation by glucose. 1. The in vitro regulation of the membrane bound adenylate cyclase of Escherichia coli B/r by a variety of carbohydrates and one mammalian hormone was examined. 2. The membrane bound adenylate cyclase was found responsive to regulation by the various growth substrates and to glucagon. 3. Solubilization of the bacterial membrane preparation by a procedure specific for the solubilization of the phosphotransferase enzyme E1 1 to its E1 1 A and E1 1 B subunits was found to be accompanied by the loss of the adenylate cyclase regulation by glucose. 4. Reconstitution of the membrane was found to result in a recovery of the regulative response of the adenylate cyclase to glucose. 5. A model for the intermediate steps in the interaction between glucose and phosphotransferase E1 1 and the adenylate cyclase is discussed."} {"id": "PMID:164931", "title": "Electrochemical regeneration of nicotinamide adenine dinucleotide.", "content": "Reduced nicotinamide adenine dinucleotide (NADH) has been characterized electrochemically by solid electrode voltammetry and controlled potential electrolysis. Photometric and enzymatic assay showed that enzymatically active nicotinamide adenine dinucleotide (NAD-+) could be regenerated electrolytically from its reduced form without the use of so-called electron mediators. Complete regeneration of enzymatically active NAD can be expected in pyrophosphate buffers and phosphate buffers during the electrolysis. Advantages of electrochemical regeneration of coenzymes are discussed, especially with regard to immobilization of enzymes.", "contents": "Electrochemical regeneration of nicotinamide adenine dinucleotide. Reduced nicotinamide adenine dinucleotide (NADH) has been characterized electrochemically by solid electrode voltammetry and controlled potential electrolysis. Photometric and enzymatic assay showed that enzymatically active nicotinamide adenine dinucleotide (NAD-+) could be regenerated electrolytically from its reduced form without the use of so-called electron mediators. Complete regeneration of enzymatically active NAD can be expected in pyrophosphate buffers and phosphate buffers during the electrolysis. Advantages of electrochemical regeneration of coenzymes are discussed, especially with regard to immobilization of enzymes."} {"id": "PMID:164932", "title": "A plausible role for a membrane-bound cyclic AMP phosphodiesterase in cellular slime mold chemotaxis.", "content": "1. Kinetics of membrane-bound cyclic AMP phosphodiesterase of the cellular slime mold, Dictyostelium discoideum, were studied under two conditions: in the 27 000 times g sediment of cell homogenates (particle-bound phosphodiesterase) and in cell suspensions using external cyclic AMP as a substrate (cell-bound phosphodiesterase). Both methods revealed non-Michaelian kinetics with interaction coefficients less than 1. 2. The membrane-bound phosphodiesterase has a specificity different from that of the cyclic AMP receptor, also present at the cell surface. 3. The membrane-bound enzyme was solubilized by lithium 3, 5-diiodosalicylate and partially purified. In this state the non-linear kinetics were still retained; however, the enzyme was not inhibited by the D. discoideum inhibitor, unlike the cell-bound phosphodiesterase in vivo. This indicates that both enzymes share an inhibitor binding site and that this site is cryptic in the cell-bound state. 4. Production of periodic cyclic AMP pulses by centers, and their relay by other cells, is believed to occur during aggregation. It is suggested that the cell-bound enzyme determines a \"time window\" significantly smaller than the period of pulsing, and optimizes stimulation of the cyclic AMP receptors in chemotaxis and signal relaying.", "contents": "A plausible role for a membrane-bound cyclic AMP phosphodiesterase in cellular slime mold chemotaxis. 1. Kinetics of membrane-bound cyclic AMP phosphodiesterase of the cellular slime mold, Dictyostelium discoideum, were studied under two conditions: in the 27 000 times g sediment of cell homogenates (particle-bound phosphodiesterase) and in cell suspensions using external cyclic AMP as a substrate (cell-bound phosphodiesterase). Both methods revealed non-Michaelian kinetics with interaction coefficients less than 1. 2. The membrane-bound phosphodiesterase has a specificity different from that of the cyclic AMP receptor, also present at the cell surface. 3. The membrane-bound enzyme was solubilized by lithium 3, 5-diiodosalicylate and partially purified. In this state the non-linear kinetics were still retained; however, the enzyme was not inhibited by the D. discoideum inhibitor, unlike the cell-bound phosphodiesterase in vivo. This indicates that both enzymes share an inhibitor binding site and that this site is cryptic in the cell-bound state. 4. Production of periodic cyclic AMP pulses by centers, and their relay by other cells, is believed to occur during aggregation. It is suggested that the cell-bound enzyme determines a \"time window\" significantly smaller than the period of pulsing, and optimizes stimulation of the cyclic AMP receptors in chemotaxis and signal relaying."} {"id": "PMID:164933", "title": "The functional metabolism of vitamin D in chicks fed low-calcium and low-phosphorus diets.", "content": "Radioactively labelled cholecalciferol was administered continuously to chicks that were fed normal, low-calcium and low-phosphorus diets. It has been possible to show that under such steady state conditions with regard to cholecalciferol, and mineral restriction, the animal reacts by increased accumulation of 1, 25-dihydroxycholecalciferol in the intestinal and the kidney cell, which was associated in the intestine with an increased calcium-binding activity. A similar accumulation of 1, 25-dihydroxycholecalciferol in bone was not noticed. It is proposed that the intestine and the kidney, but not bone, are the main target organs for cholecalciferol in the maintenance of calcium homeostasis, and that both calcium and phosphorus play a role in the regulation of the formation and subsequent function of 1, 25-dihydroxycholecalciferol.", "contents": "The functional metabolism of vitamin D in chicks fed low-calcium and low-phosphorus diets. Radioactively labelled cholecalciferol was administered continuously to chicks that were fed normal, low-calcium and low-phosphorus diets. It has been possible to show that under such steady state conditions with regard to cholecalciferol, and mineral restriction, the animal reacts by increased accumulation of 1, 25-dihydroxycholecalciferol in the intestinal and the kidney cell, which was associated in the intestine with an increased calcium-binding activity. A similar accumulation of 1, 25-dihydroxycholecalciferol in bone was not noticed. It is proposed that the intestine and the kidney, but not bone, are the main target organs for cholecalciferol in the maintenance of calcium homeostasis, and that both calcium and phosphorus play a role in the regulation of the formation and subsequent function of 1, 25-dihydroxycholecalciferol."} {"id": "PMID:164934", "title": "Essential arginine residues in D-glyceraldehyde-3-phosphate dehydrogenase.", "content": "Two arginyl residues per subunit of yeast D-glyceraldehyde-3-phoshphate dehydrogenase were modified by treatment with butanedione without significant changes in the compostion of other amino acid residues. The modified enzyme displays no dehydrogenase activity. It retains the capacity for interacting with the coenzyme NAD, but binds it less firmly than does the native enzyme. The molar absorbance of the enzyme-NAD complex is markedly reduced and the reactivity of the active-center SH groups is changed in the modified enzyme. The native and modified enzymes show identical fluorescence spectra, absorbance and CD spectra.", "contents": "Essential arginine residues in D-glyceraldehyde-3-phosphate dehydrogenase. Two arginyl residues per subunit of yeast D-glyceraldehyde-3-phoshphate dehydrogenase were modified by treatment with butanedione without significant changes in the compostion of other amino acid residues. The modified enzyme displays no dehydrogenase activity. It retains the capacity for interacting with the coenzyme NAD, but binds it less firmly than does the native enzyme. The molar absorbance of the enzyme-NAD complex is markedly reduced and the reactivity of the active-center SH groups is changed in the modified enzyme. The native and modified enzymes show identical fluorescence spectra, absorbance and CD spectra."} {"id": "PMID:164935", "title": "Application of affinity chromatography to the purification of collagenase for the isolation of insoluble elastin.", "content": "ClostrIdium histolyticum collagenase (clostridiopeptidase A, EC 3.4.4.19) was purified by batchwise separation with DEAE-cellulose followed by affinity chromatography on a column of alkali-treated elastin. The N-terminal amino acid profile of elastin isolated from bovine ligamentum nuchae using this enzyme preparation was compared with that of a duplicate sample purified with a mixture of collagenase I and II (Yoshida, E, and Noda, H. (1965) Biochim. Biopsys. Acta 105, 562-574). An approx. three-fold decrease in the molar concentration of N-terminal residues and a considerable reduction in their number was obtained by using the former enzyme preparation.", "contents": "Application of affinity chromatography to the purification of collagenase for the isolation of insoluble elastin. ClostrIdium histolyticum collagenase (clostridiopeptidase A, EC 3.4.4.19) was purified by batchwise separation with DEAE-cellulose followed by affinity chromatography on a column of alkali-treated elastin. The N-terminal amino acid profile of elastin isolated from bovine ligamentum nuchae using this enzyme preparation was compared with that of a duplicate sample purified with a mixture of collagenase I and II (Yoshida, E, and Noda, H. (1965) Biochim. Biopsys. Acta 105, 562-574). An approx. three-fold decrease in the molar concentration of N-terminal residues and a considerable reduction in their number was obtained by using the former enzyme preparation."} {"id": "PMID:164936", "title": "Magnetic circular dichroism studies on microsomal aryl hydrocarbon hydroxylase: comparison with cytochrome b-5 and cytochrome P-450-cam.", "content": "Magnetic circular dichroism spectra are reported for the visible and near ultraviolet spectral regions of liver microsomes from dimethylbenzanthracene-treated rats. The sequential addition of NADH, dithionite, and carbon monoxide enables us to determine contributions to the magnetic circular dichroism by cytochromes b-5 and P-450, which dominate the spectra. The magnetic circular dichroism of the microsomal preparation is compared with that of purified oxidized and reduced cytochrome -b-5 from pig liver and with the camphor-complexed and camphor-free oxidized, reduced, and reduced carbonmonoxy cytochrome P-450-cam from Pseudomonas putida. The magnetic circular dichroism spectra of the membrane bound cytochrome -b-5 are similar to those of the purified protein, indicating that little or no alteration in the environment of the heme occurs during the isolation procedure. The soluble bacterial cytochrome P-450 also appears to be a suitable model for microsomal P-450, although differences in the magnetic circular dichroism intensity are observed for the two enzymes. No effect of dimethylbenzanthracene on the magnetic circular dichroism spectra of induced compared to control rat microsomes could be observed.", "contents": "Magnetic circular dichroism studies on microsomal aryl hydrocarbon hydroxylase: comparison with cytochrome b-5 and cytochrome P-450-cam. Magnetic circular dichroism spectra are reported for the visible and near ultraviolet spectral regions of liver microsomes from dimethylbenzanthracene-treated rats. The sequential addition of NADH, dithionite, and carbon monoxide enables us to determine contributions to the magnetic circular dichroism by cytochromes b-5 and P-450, which dominate the spectra. The magnetic circular dichroism of the microsomal preparation is compared with that of purified oxidized and reduced cytochrome -b-5 from pig liver and with the camphor-complexed and camphor-free oxidized, reduced, and reduced carbonmonoxy cytochrome P-450-cam from Pseudomonas putida. The magnetic circular dichroism spectra of the membrane bound cytochrome -b-5 are similar to those of the purified protein, indicating that little or no alteration in the environment of the heme occurs during the isolation procedure. The soluble bacterial cytochrome P-450 also appears to be a suitable model for microsomal P-450, although differences in the magnetic circular dichroism intensity are observed for the two enzymes. No effect of dimethylbenzanthracene on the magnetic circular dichroism spectra of induced compared to control rat microsomes could be observed."} {"id": "PMID:164937", "title": "Separation of respiratory reactions in Rhodospirillum rubrum: inhibition studies with 2-hydroxydiphenyl.", "content": "1. Respiration of chemotrophically and phototrophically grown Rhodospirillum rubrum is inhibited by 2-hydroxydiphenyl. 2. Membrane-bound NADH oxidase and NADH: cytochrome c reductase are inhibited also. The inhibitor constant for both reactions (Ki) is 0.075 plus or minus 0.012 mM. NADH dehydrogenase is not inhibited significantly. 3. The inhibition of succinate:cytochrome c reductase is associated for chemotrophic membranes with Ki equals 0.22 plus or minus 0.03 mM and for phototrophic membranes with Ki equals 0.49 plus or minus 0.09 mM. Succinate dehydrogenase is not affected by 2-hydroxydiphenyl. 4. Cytochrome oxidase is inhibited only slightly. 5. While NADH-dependent reactions in both phototrophic and chemotrophic membranes are inhibited maximally more than 95 percent, succinate-dependent reactions can be inhibited more than 95 percent only in chemotrophic membranes. In phototrophic membranes the maximum inhibition of succinate-dependent reactions is about 70 percent. 6. The type of inhibition in both cases 2 and 3 is non-competitive. 7. While the reduction of b-type cytochrome is inhibited by 2-hydroxydiphenyl, the degree of ubiquinone reduction is not influenced. The data suggest that the site of inhibition is localized between ubiquinone and cytochrome b. 8. Implications of these data for the respiratory electron transport system in R. rubrum are discussed.", "contents": "Separation of respiratory reactions in Rhodospirillum rubrum: inhibition studies with 2-hydroxydiphenyl. 1. Respiration of chemotrophically and phototrophically grown Rhodospirillum rubrum is inhibited by 2-hydroxydiphenyl. 2. Membrane-bound NADH oxidase and NADH: cytochrome c reductase are inhibited also. The inhibitor constant for both reactions (Ki) is 0.075 plus or minus 0.012 mM. NADH dehydrogenase is not inhibited significantly. 3. The inhibition of succinate:cytochrome c reductase is associated for chemotrophic membranes with Ki equals 0.22 plus or minus 0.03 mM and for phototrophic membranes with Ki equals 0.49 plus or minus 0.09 mM. Succinate dehydrogenase is not affected by 2-hydroxydiphenyl. 4. Cytochrome oxidase is inhibited only slightly. 5. While NADH-dependent reactions in both phototrophic and chemotrophic membranes are inhibited maximally more than 95 percent, succinate-dependent reactions can be inhibited more than 95 percent only in chemotrophic membranes. In phototrophic membranes the maximum inhibition of succinate-dependent reactions is about 70 percent. 6. The type of inhibition in both cases 2 and 3 is non-competitive. 7. While the reduction of b-type cytochrome is inhibited by 2-hydroxydiphenyl, the degree of ubiquinone reduction is not influenced. The data suggest that the site of inhibition is localized between ubiquinone and cytochrome b. 8. Implications of these data for the respiratory electron transport system in R. rubrum are discussed."} {"id": "PMID:164938", "title": "Kinetic study of oxygen evolution parameters in Triswashed, reactivated chloroplasts.", "content": "Tris-washed chloroplasts which have lost the ability to evolve oxygen can be reactivated by the procedure of Yamashita T., Tsuji, J. and Tomita G. (1971) Plant Cell Physiol. 12, 117-126) [7] to give 100 percent of the rate of control chloroplasts in continuous illumination. Furthermore, in flashing light the reactivated chloroplasts exhibit oxygen-yield oscillations of period four that are characteristic of the control. Similar kinetic parameters for intermediate steps in the water-splitting process are observed for the two preparations. We conclude that the reactivation procedure restores the native oxygen evolution mechanism to Tris-washed chloroplasts. A relatively rapid and reversible (0.5 s decay) light-induced component of EPR Signal II is observed upon inhibition of O2 evolution by Tris washing (Babcock G. T. and Sauer, K. (1975) Biochim. Biophys. Acta 376, 315-328) [10]. Reactivated chloroplasts are similar to untreated chloroplasts in that this Signal IItransient is not observed. Manganese, which is released by Tris treatment to the interior of the thylakoid membrane in an EPR-detectable state, is returned to an EPR-undetectable state by reactivation. The reactivation procedure does not require light to restore O2 evolution and EDTA has no effect on the extent of reactivation. These results are discussed in terms of possible mechanisms for manganese incorporation into photosynthetic membranes.", "contents": "Kinetic study of oxygen evolution parameters in Triswashed, reactivated chloroplasts. Tris-washed chloroplasts which have lost the ability to evolve oxygen can be reactivated by the procedure of Yamashita T., Tsuji, J. and Tomita G. (1971) Plant Cell Physiol. 12, 117-126) [7] to give 100 percent of the rate of control chloroplasts in continuous illumination. Furthermore, in flashing light the reactivated chloroplasts exhibit oxygen-yield oscillations of period four that are characteristic of the control. Similar kinetic parameters for intermediate steps in the water-splitting process are observed for the two preparations. We conclude that the reactivation procedure restores the native oxygen evolution mechanism to Tris-washed chloroplasts. A relatively rapid and reversible (0.5 s decay) light-induced component of EPR Signal II is observed upon inhibition of O2 evolution by Tris washing (Babcock G. T. and Sauer, K. (1975) Biochim. Biophys. Acta 376, 315-328) [10]. Reactivated chloroplasts are similar to untreated chloroplasts in that this Signal IItransient is not observed. Manganese, which is released by Tris treatment to the interior of the thylakoid membrane in an EPR-detectable state, is returned to an EPR-undetectable state by reactivation. The reactivation procedure does not require light to restore O2 evolution and EDTA has no effect on the extent of reactivation. These results are discussed in terms of possible mechanisms for manganese incorporation into photosynthetic membranes."} {"id": "PMID:164939", "title": "The tiron free radical as a sensitive indicator of chloroplastic photoautoxidation.", "content": "Wheat chloroplasts photochemically reduced molecular oxygen, as a Hill oxidant in the Mehler reaction, to superoxide anion which then oxidized added 1,2-dihydroxybenzene-3,5-disulfonate to its semiquinone, a comparatively stable free radical at pH 7. The last mentioned reaction was rapid in aqueous solution, but the rate of formation of 1,2-dihydroxybenzene-3,5-disulfonate semiquinone by the chloroplast system was calculated as T1 of 0.6 s. The Mehler reaction, or more specifically the univalent reduction of oxygen by Photosystem I, was rate-limiting so that the 1,2-dihydroxybenzene-3,5-disulfonate seniquinone was a useful spin probe for superoxide anion production at room temperature. The ESR signal of 1,2-dihydroxybenzene-3,5-disulfonate semiquinone was proportional to its steady state concentration and decayed in the dark with a T1/2 of 5-6 s. This oxygen-dependent signal was enhanced by mediation of chloroplastic oxygen reduction through methyl viologen. The superoxide anion scavengers ascorbate and L-epinephrine competitively obscured 1,2-dihydroxybenzene-3,5-disulfonate semiquinone formation, butadded superoxide dismutase was not as effective in this role. Partial inhibition by superoxide dismutase was achieved only by preincubation of Photosystem I enriched particles with ten times the endogenous concentration of superoxide dismutase. This and the persistence of a small amount of a 1,2-dihydroxybenzene-3,5-disulfonate (Tiron) oxidizing species in the dark supports the concept of Tiron accessibility but not the superoxide dismutase accessibility of superoxide anion bound in its formative enzyme complex. Benzoquinone and naphthoquinone disulfonate also reacted with superoxide anion, and supported both the Hill reaction and the Mehler reaction as final oxidants of both water and superoxide anion.", "contents": "The tiron free radical as a sensitive indicator of chloroplastic photoautoxidation. Wheat chloroplasts photochemically reduced molecular oxygen, as a Hill oxidant in the Mehler reaction, to superoxide anion which then oxidized added 1,2-dihydroxybenzene-3,5-disulfonate to its semiquinone, a comparatively stable free radical at pH 7. The last mentioned reaction was rapid in aqueous solution, but the rate of formation of 1,2-dihydroxybenzene-3,5-disulfonate semiquinone by the chloroplast system was calculated as T1 of 0.6 s. The Mehler reaction, or more specifically the univalent reduction of oxygen by Photosystem I, was rate-limiting so that the 1,2-dihydroxybenzene-3,5-disulfonate seniquinone was a useful spin probe for superoxide anion production at room temperature. The ESR signal of 1,2-dihydroxybenzene-3,5-disulfonate semiquinone was proportional to its steady state concentration and decayed in the dark with a T1/2 of 5-6 s. This oxygen-dependent signal was enhanced by mediation of chloroplastic oxygen reduction through methyl viologen. The superoxide anion scavengers ascorbate and L-epinephrine competitively obscured 1,2-dihydroxybenzene-3,5-disulfonate semiquinone formation, butadded superoxide dismutase was not as effective in this role. Partial inhibition by superoxide dismutase was achieved only by preincubation of Photosystem I enriched particles with ten times the endogenous concentration of superoxide dismutase. This and the persistence of a small amount of a 1,2-dihydroxybenzene-3,5-disulfonate (Tiron) oxidizing species in the dark supports the concept of Tiron accessibility but not the superoxide dismutase accessibility of superoxide anion bound in its formative enzyme complex. Benzoquinone and naphthoquinone disulfonate also reacted with superoxide anion, and supported both the Hill reaction and the Mehler reaction as final oxidants of both water and superoxide anion."} {"id": "PMID:164940", "title": "Biochemical and biophysical studies on cytochrome c oxidase. XX. Reaction with sulphide.", "content": "1. Upon addition of sulphide to oxidized cytochrome c oxidase, a low-spin heme sulphide compound is formed with an EPR signal at gx = 2.54, gy = 2.23 and gz = 1.87. Concomitantly with the formation of this signal the EPR-detectable low-spin heme signal at g = 3 and the copper signal near g = 2 decrease in intensity, pointing to a partial reduction of the enzyme by sulphide. 2. The addition of sulphide to cytochrome c oxidase, previously reduced in the presence of azide or cyanide, brings about a disappearance of the azido-cytochrome c oxidase signal at gx = 2.9, gy = 2.2, and gz = 1.67 and a decrease of the signal at g = 3.6 of cyano-cytochrome c oxidase. Concomitantly the sulphide-induced EPR signal is formed. 3. These observations demonstrate that azide, cyanide and sulphide are competitive for an oxidized binding site on cytochrome c oxidase. Moreover, it is shown that the affinity of cyanide and sulphide for this site is greater than that of azide.", "contents": "Biochemical and biophysical studies on cytochrome c oxidase. XX. Reaction with sulphide. 1. Upon addition of sulphide to oxidized cytochrome c oxidase, a low-spin heme sulphide compound is formed with an EPR signal at gx = 2.54, gy = 2.23 and gz = 1.87. Concomitantly with the formation of this signal the EPR-detectable low-spin heme signal at g = 3 and the copper signal near g = 2 decrease in intensity, pointing to a partial reduction of the enzyme by sulphide. 2. The addition of sulphide to cytochrome c oxidase, previously reduced in the presence of azide or cyanide, brings about a disappearance of the azido-cytochrome c oxidase signal at gx = 2.9, gy = 2.2, and gz = 1.67 and a decrease of the signal at g = 3.6 of cyano-cytochrome c oxidase. Concomitantly the sulphide-induced EPR signal is formed. 3. These observations demonstrate that azide, cyanide and sulphide are competitive for an oxidized binding site on cytochrome c oxidase. Moreover, it is shown that the affinity of cyanide and sulphide for this site is greater than that of azide."} {"id": "PMID:164941", "title": "Asymmetry of an energy transducing membrane the location of cytochrome c2 in Rhodopseudomonas spheroides and Rhodopseudomonas capsulata.", "content": "Monospecific antibodies have been prepared against cytochrome c2 from Rhodopseudomonas spheroides and Rhodopseudomonas capsulata, and against cytochrome c' from Rps. capsulata. These antibodies precipitated their respective antigens, but did not cross react with a wide range of procaryotic or eucaryotic cytochromes, or with other bacterial proteins. The cytochromes produced during aerobic growth were immunologically indistinguishable from those produced during photosynthetic growth. Cytochrome c2 is located in vivo in the periplasmic space between the cell was and the cell membrane, and when chromatophores are prepared from whole cells the cytochrome becomes trapped inside these vesicles. The implications of these results to energy coupling in the photosynthetic bacteria are discussed.", "contents": "Asymmetry of an energy transducing membrane the location of cytochrome c2 in Rhodopseudomonas spheroides and Rhodopseudomonas capsulata. Monospecific antibodies have been prepared against cytochrome c2 from Rhodopseudomonas spheroides and Rhodopseudomonas capsulata, and against cytochrome c' from Rps. capsulata. These antibodies precipitated their respective antigens, but did not cross react with a wide range of procaryotic or eucaryotic cytochromes, or with other bacterial proteins. The cytochromes produced during aerobic growth were immunologically indistinguishable from those produced during photosynthetic growth. Cytochrome c2 is located in vivo in the periplasmic space between the cell was and the cell membrane, and when chromatophores are prepared from whole cells the cytochrome becomes trapped inside these vesicles. The implications of these results to energy coupling in the photosynthetic bacteria are discussed."} {"id": "PMID:164942", "title": "Metabolism of lipoproteins in nonhuman primates. Studies on the origin of low density lipoprotein apoprotein in the plasma of the squirrel monkey.", "content": "The plasma of squirrel monkeys contains extremely low levels of very low density lipoproteins. The delipidated apoproteins from the different lipoprotein density classes of this species show a heterogeneity similar to that of man and the rat. The biosynthesis of the apoproteins of squirrel monkey lipoproteins was studied in fasted normal and Triton WR1339-treated animals. After intravenous injection of [3-H] leucine, maximal labeling of very low density lipoproteins occurred after 1 h, intermediate density lipoproteins (d 1.006--1.019) in 2 h, and low density lipoproteins after 3 h. At all times, however, low density lipoproteins had the greatest percentage of radioactivity. Polyacrylamide gel electrophoresis revealed that the apoprotein B moiety of very low density and intermediate density lipoproteins contained 62% and 81% of the total radioactivity in these lipoproteins whereas the fast-migrating peptides were minimally labeled. In monkeys injected with Triton WR1339, 70--80% of the radioactivity incorporated into d smaller than 1.063 lipoproteins was in very low density lipoproteins with only 10--15% in intermediate and low density lipoproteins. After injection of 3-H-labeled very low density lipoproteins and [14-C] leucine into Triton-treated monkeys, catabolism of 3-H-labeled very low density lipoprotein to intermediate and low density lipoproteins was small and was significantly less than corresponding values for the incorporation of [14-C] leucine. Thus, breakdown of very low density lipoproteins could not account for all the labeled apoprotein B present in the intermediate and low density lipoprotein fractions. The results indicate that most, but not all, of the newly synthesized apoprotein B enters plasma in very low density lipoproteins and that the low concentrations of this lipoprotein in squirrel monkey plasma are a consequence of its rapid turnover.", "contents": "Metabolism of lipoproteins in nonhuman primates. Studies on the origin of low density lipoprotein apoprotein in the plasma of the squirrel monkey. The plasma of squirrel monkeys contains extremely low levels of very low density lipoproteins. The delipidated apoproteins from the different lipoprotein density classes of this species show a heterogeneity similar to that of man and the rat. The biosynthesis of the apoproteins of squirrel monkey lipoproteins was studied in fasted normal and Triton WR1339-treated animals. After intravenous injection of [3-H] leucine, maximal labeling of very low density lipoproteins occurred after 1 h, intermediate density lipoproteins (d 1.006--1.019) in 2 h, and low density lipoproteins after 3 h. At all times, however, low density lipoproteins had the greatest percentage of radioactivity. Polyacrylamide gel electrophoresis revealed that the apoprotein B moiety of very low density and intermediate density lipoproteins contained 62% and 81% of the total radioactivity in these lipoproteins whereas the fast-migrating peptides were minimally labeled. In monkeys injected with Triton WR1339, 70--80% of the radioactivity incorporated into d smaller than 1.063 lipoproteins was in very low density lipoproteins with only 10--15% in intermediate and low density lipoproteins. After injection of 3-H-labeled very low density lipoproteins and [14-C] leucine into Triton-treated monkeys, catabolism of 3-H-labeled very low density lipoprotein to intermediate and low density lipoproteins was small and was significantly less than corresponding values for the incorporation of [14-C] leucine. Thus, breakdown of very low density lipoproteins could not account for all the labeled apoprotein B present in the intermediate and low density lipoprotein fractions. The results indicate that most, but not all, of the newly synthesized apoprotein B enters plasma in very low density lipoproteins and that the low concentrations of this lipoprotein in squirrel monkey plasma are a consequence of its rapid turnover."} {"id": "PMID:164943", "title": "Lipoprotein-acid mucopolysaccharide complexes of human atherosclerotic lesions.", "content": "Lipoprotein-acid mucopolysaccharide complexes occurring in different types of human atherosclerotic lesions were isolated and partially characterized. Complexes from fatty streaks and fibrous plaques were extracted from pooled tissues with 0.15 M NaCl, purified by gel filtration, and fractionated by ultracentrifugation. Both low and very low density lipoproteins were present; low density lipoprotein was predominant. The complexes were analyzed for uronic acid, cholesterol, phospholipid, and Ca-2+ contents; there was no significant difference in the relative molar ratios between complexes from fatty streaks and fibrous plaques. Acid mucopolysaccharides were isolated from the complexes and identified by electrophoresis and enzymatic studies. Chondroitin sulfate C and hyaluronic acid were found in complexes from fatty streaks and fibrous plaques. Heparin was detected only in fibrous plaques.", "contents": "Lipoprotein-acid mucopolysaccharide complexes of human atherosclerotic lesions. Lipoprotein-acid mucopolysaccharide complexes occurring in different types of human atherosclerotic lesions were isolated and partially characterized. Complexes from fatty streaks and fibrous plaques were extracted from pooled tissues with 0.15 M NaCl, purified by gel filtration, and fractionated by ultracentrifugation. Both low and very low density lipoproteins were present; low density lipoprotein was predominant. The complexes were analyzed for uronic acid, cholesterol, phospholipid, and Ca-2+ contents; there was no significant difference in the relative molar ratios between complexes from fatty streaks and fibrous plaques. Acid mucopolysaccharides were isolated from the complexes and identified by electrophoresis and enzymatic studies. Chondroitin sulfate C and hyaluronic acid were found in complexes from fatty streaks and fibrous plaques. Heparin was detected only in fibrous plaques."} {"id": "PMID:164944", "title": "Fluorescence quenching in lecithin and lecithin/cholesterol liposomes by parmagenetic lipid analogues. Introduction of a new probe approach.", "content": "1. Perylene, whether incorporated into lecithin or lecithin/cholesterol (1:1) liposomes, exhibits identical fluorescence spectra, but fluorescence in the presence of cholesterol is enhanced by 30-50%. 2. The fluorescence of perylene in pure dipalmitoyllecithin vesicles increases sharply at the transition temperature (Tt equals 41 degrees C). No such fluorescence jump is observed in lecithin/cholesterol (1:1) micelles. 3. In lecithin liposomes maximal quenching of perylene fluorescence at 25 degrees C is effected by cholestane spin label (80%) followed by androstane spin label (70%), 5-nitroxide stearate (60%) and 16-nitroxide stearate (50%). 4. In liposomes containing 5 mol % cholesterol these differences are reduced; however, the sequence of quenching efficiencies is the same except for the nitroxide stearates, which interchange their positions. 5. 5. Paramagnetic quenching of perylene fluorescence is stable below 35 degrees C and above 45 degrees C, but decreases sharply about the phase-transition temperature of dipalmitoyllecithin. 6. In lecithin/cholesterol (1:1, molar ratio) lipsomes fluorescence quenching diminishes linearly, but only slightly, with increasing temperature. 7. Cholestane spin label and androstane spin label at concentrations of greater than 20 mol % themselves suppress the quenching discontinuity at Tt, indicating a cholesterol-like structural effect. 8. The quenching phenomena observed are attributed to a non-random accommodation of fluorophore and quencher molecules (co-clustering) below the phase transition and a statistical distribution of both impurities above Tt. 9. In the presence of cholesterol the clustering tendencies are reduced or even eliminated; this is compatible with the concept that cholesterol fluidizes the phosphatide acyl chains below the transtion temperature.", "contents": "Fluorescence quenching in lecithin and lecithin/cholesterol liposomes by parmagenetic lipid analogues. Introduction of a new probe approach. 1. Perylene, whether incorporated into lecithin or lecithin/cholesterol (1:1) liposomes, exhibits identical fluorescence spectra, but fluorescence in the presence of cholesterol is enhanced by 30-50%. 2. The fluorescence of perylene in pure dipalmitoyllecithin vesicles increases sharply at the transition temperature (Tt equals 41 degrees C). No such fluorescence jump is observed in lecithin/cholesterol (1:1) micelles. 3. In lecithin liposomes maximal quenching of perylene fluorescence at 25 degrees C is effected by cholestane spin label (80%) followed by androstane spin label (70%), 5-nitroxide stearate (60%) and 16-nitroxide stearate (50%). 4. In liposomes containing 5 mol % cholesterol these differences are reduced; however, the sequence of quenching efficiencies is the same except for the nitroxide stearates, which interchange their positions. 5. 5. Paramagnetic quenching of perylene fluorescence is stable below 35 degrees C and above 45 degrees C, but decreases sharply about the phase-transition temperature of dipalmitoyllecithin. 6. In lecithin/cholesterol (1:1, molar ratio) lipsomes fluorescence quenching diminishes linearly, but only slightly, with increasing temperature. 7. Cholestane spin label and androstane spin label at concentrations of greater than 20 mol % themselves suppress the quenching discontinuity at Tt, indicating a cholesterol-like structural effect. 8. The quenching phenomena observed are attributed to a non-random accommodation of fluorophore and quencher molecules (co-clustering) below the phase transition and a statistical distribution of both impurities above Tt. 9. In the presence of cholesterol the clustering tendencies are reduced or even eliminated; this is compatible with the concept that cholesterol fluidizes the phosphatide acyl chains below the transtion temperature."} {"id": "PMID:164945", "title": "Sialoglycopeptides from bovine milk fat globule membrane.", "content": "Milk fat globule membrane was shown to contain sialic acid, all of which could be released without disruption of the fat globule. Sialoglycopeptides were cleaved from the surface of intact fat globules by Pronase and fractionated on Sephadex G-50. Further fractionation of the major sialoglycopeptide peak on DEAE-Sephadex gave two groups of sialoglycopeptides eluted with 0.1 M NaCl (Group A) and 0.5 M NaCl (Group B), respectively. Refractionation gave a major sialoglycopeptide from each of the two groups together with a total of three minor sialoglycopeptides. All five sialoglycopeptides eluted as single peaks using shallow salt gradients on DEAE-Sephadex and contained a hydrophilic peptide chain together with galactose, mannose, N-acetylgalactosamine, N-acetylglucosamine, and sialic acid. Glycopeptides of Group A but not Group B contained fucose. The major sialoglycopeptide of Group B released 35% of its hexose and hexosamine on treatment with alkaline borohydride leaving a sialoglycopeptide which had reduced serine and threonine and elevated alanine levels and in addition contained 2-aminobutyric acid. An oligosaccharide fraction containing N-acetylgalactosaminitol, galactose and sialic acid in a molar ratio of 1:1:2 was partially characterised from the clevage mixture. The major sialoglycopeptide of Group A had a more complex carbohydrate structure and showed no released carbohydrate on treatment with alkaline borohydride. The sialoglycopeptides of milk fat globule membrane show many similarities with those of erythrocyte membrane and have a potential use in comparative and structural studies.", "contents": "Sialoglycopeptides from bovine milk fat globule membrane. Milk fat globule membrane was shown to contain sialic acid, all of which could be released without disruption of the fat globule. Sialoglycopeptides were cleaved from the surface of intact fat globules by Pronase and fractionated on Sephadex G-50. Further fractionation of the major sialoglycopeptide peak on DEAE-Sephadex gave two groups of sialoglycopeptides eluted with 0.1 M NaCl (Group A) and 0.5 M NaCl (Group B), respectively. Refractionation gave a major sialoglycopeptide from each of the two groups together with a total of three minor sialoglycopeptides. All five sialoglycopeptides eluted as single peaks using shallow salt gradients on DEAE-Sephadex and contained a hydrophilic peptide chain together with galactose, mannose, N-acetylgalactosamine, N-acetylglucosamine, and sialic acid. Glycopeptides of Group A but not Group B contained fucose. The major sialoglycopeptide of Group B released 35% of its hexose and hexosamine on treatment with alkaline borohydride leaving a sialoglycopeptide which had reduced serine and threonine and elevated alanine levels and in addition contained 2-aminobutyric acid. An oligosaccharide fraction containing N-acetylgalactosaminitol, galactose and sialic acid in a molar ratio of 1:1:2 was partially characterised from the clevage mixture. The major sialoglycopeptide of Group A had a more complex carbohydrate structure and showed no released carbohydrate on treatment with alkaline borohydride. The sialoglycopeptides of milk fat globule membrane show many similarities with those of erythrocyte membrane and have a potential use in comparative and structural studies."} {"id": "PMID:164946", "title": "Relationship between L-alanine and sodium ion transport in isolated renal tubules.", "content": "1. Rat renal tubules were isolated by incubation with collagenase. The Na+ concentration in the tubules at 37 degrees C was increased by additions of g-strophantin and L-alanine. The increase of Na+ in the presence of both g-strophantin and L-alanine was stronger than with either alone. 2. Radioactive sodium (22-Na), which was taken up by the tubules at 0 degrees C in K+-free medium, was more slowly washed out in the buffer with added g-strophantin than in the control buffer, but L-alanine had no effect. 3. At 0 degrees C incubation without K+, g-strophantin did not affect the 22-Na transport of the tubules. But under the same conditions, L-alanine increased Na+ uptake significantly, and in conjunction with it, L-alanine uptake was also increased. 4. The relationship between L-alanine uptake and intra- extracellular Na+ concentration gradients was linear. The ration of L-alanine to Na+ uptake at 0 degrees C was about 1:2. 5. In the incubation without K+ at 0 degrees C, L-alanine could be accumulated in tubules against the chemical concentration gradient (about 1.5-fold). 6. In the incubation without K+ at 37 degrees C, the L-alanine concentration in tubules after 5 min was already steady (Ci/Ce = 2.2), but with K+ it was not stabilized after 10 min. The ration Ci/Ce with K+ WAS HIGHER THAN WITHOUT K+. 7. G-Strophantin, p-hydroxymercuribenzoate, amiloride, and 2,4-dinitrophenol inhibited L-alanine uptake in the tubules and at the same time increased Na+ concentration. The relationship between the L-alanine uptakes inhibited by g-strophantin, amiloride and dinitrophenol, and the respective intra- extracellular Na+ concentration gradients was strikingly linear. But in the case of p-hydroxymercuribenzoate there was no correlation. 8. The results indicate that L-alanine transport into the renal tubules might be regulated mainly by the intra- extracellular Na+ concentration gradient and that inhibitors such as g-strophantin, amiloride, and dinitrophenol could have a secondary effect on the L-alanine transport which follows the change of Na+ concentration in cells. p-Hydroxymercuribenzoate might have an inhibiting effect on the binding of carrier with Na+ and/or L-alanine.", "contents": "Relationship between L-alanine and sodium ion transport in isolated renal tubules. 1. Rat renal tubules were isolated by incubation with collagenase. The Na+ concentration in the tubules at 37 degrees C was increased by additions of g-strophantin and L-alanine. The increase of Na+ in the presence of both g-strophantin and L-alanine was stronger than with either alone. 2. Radioactive sodium (22-Na), which was taken up by the tubules at 0 degrees C in K+-free medium, was more slowly washed out in the buffer with added g-strophantin than in the control buffer, but L-alanine had no effect. 3. At 0 degrees C incubation without K+, g-strophantin did not affect the 22-Na transport of the tubules. But under the same conditions, L-alanine increased Na+ uptake significantly, and in conjunction with it, L-alanine uptake was also increased. 4. The relationship between L-alanine uptake and intra- extracellular Na+ concentration gradients was linear. The ration of L-alanine to Na+ uptake at 0 degrees C was about 1:2. 5. In the incubation without K+ at 0 degrees C, L-alanine could be accumulated in tubules against the chemical concentration gradient (about 1.5-fold). 6. In the incubation without K+ at 37 degrees C, the L-alanine concentration in tubules after 5 min was already steady (Ci/Ce = 2.2), but with K+ it was not stabilized after 10 min. The ration Ci/Ce with K+ WAS HIGHER THAN WITHOUT K+. 7. G-Strophantin, p-hydroxymercuribenzoate, amiloride, and 2,4-dinitrophenol inhibited L-alanine uptake in the tubules and at the same time increased Na+ concentration. The relationship between the L-alanine uptakes inhibited by g-strophantin, amiloride and dinitrophenol, and the respective intra- extracellular Na+ concentration gradients was strikingly linear. But in the case of p-hydroxymercuribenzoate there was no correlation. 8. The results indicate that L-alanine transport into the renal tubules might be regulated mainly by the intra- extracellular Na+ concentration gradient and that inhibitors such as g-strophantin, amiloride, and dinitrophenol could have a secondary effect on the L-alanine transport which follows the change of Na+ concentration in cells. p-Hydroxymercuribenzoate might have an inhibiting effect on the binding of carrier with Na+ and/or L-alanine."} {"id": "PMID:164947", "title": "Microsomal (Na- +K+)-activated ATPase from frog skin epithelium. Cation activations and some effects of inhibitors.", "content": "A method is described for the extraction of microsomal ouabain-sensitive (a- + K+)-activated ATPase from separated frog skin epithelium. The method yields a microsomal fraction containing (Na+ K+)-stimulated activity in the range of 30- 40 nmol - mg -1 - min -1 at 26 degrees C. This portion which is also ouabain sensitive, is about half of the total activity in media containing Mg2+, Na+ and K+. These preparations also contain Mg2+-dependent or Ca2+-dependent activities which are not additive and which are not significantly affected by ouabain, Na+, K+ or Li+. The activations of the ouabain-sensitive ATPase activity by Mg2+, Na+, and K+ are similar to those described in other tissues. It is found that Li+ does not substitute for Na+ as an activator but in high concentrations does produce partial activation in the presence of Na+ with no K+. These results are pertinent to the reported observations of ouabain-sensitive Li+ flux across frog skin. It is concluded that this flux is not apparently due to a direct activating effect of Li+ on the sodium pump.", "contents": "Microsomal (Na- +K+)-activated ATPase from frog skin epithelium. Cation activations and some effects of inhibitors. A method is described for the extraction of microsomal ouabain-sensitive (a- + K+)-activated ATPase from separated frog skin epithelium. The method yields a microsomal fraction containing (Na+ K+)-stimulated activity in the range of 30- 40 nmol - mg -1 - min -1 at 26 degrees C. This portion which is also ouabain sensitive, is about half of the total activity in media containing Mg2+, Na+ and K+. These preparations also contain Mg2+-dependent or Ca2+-dependent activities which are not additive and which are not significantly affected by ouabain, Na+, K+ or Li+. The activations of the ouabain-sensitive ATPase activity by Mg2+, Na+, and K+ are similar to those described in other tissues. It is found that Li+ does not substitute for Na+ as an activator but in high concentrations does produce partial activation in the presence of Na+ with no K+. These results are pertinent to the reported observations of ouabain-sensitive Li+ flux across frog skin. It is concluded that this flux is not apparently due to a direct activating effect of Li+ on the sodium pump."} {"id": "PMID:164948", "title": "Enhancement of the activity of asparaginyl-tRNA synthetase by an activator from rabbit liver.", "content": "Asparaginyl-tRNA synthetase has been partially purified from acetone powders of rabbit liver. (NH-4)-2SO-4 fractionation was followed by chromatography of the enzyme on DEAE-cellulose. An activator separated from the enzyme. Further chromatography on Sephadex G-100 and G-200 showed that the latter consisted of two components. The smaller of these (mol wt is approximately equal to 35 000) possessed enzyme transfer activity but the larger one (mol wt 80 000-90 000) required the addition of activator before any enzyme transfer activity was demonstrable. The activator itself was devoid of transfer activity. After chromatography of crude extracts of asparaginyl-tRNA synthetase on Sepharose 4B the activity in the enzyme peak, which was of considerably larger molecular weight than any of the fractions found after purification could be enhanced by addition of the activator. None of the fractions of the enzyme or of activator catalysed any extensive asparagine-dependent ATP-PP-i exchange, either in the presence or the absence of added tRNA.", "contents": "Enhancement of the activity of asparaginyl-tRNA synthetase by an activator from rabbit liver. Asparaginyl-tRNA synthetase has been partially purified from acetone powders of rabbit liver. (NH-4)-2SO-4 fractionation was followed by chromatography of the enzyme on DEAE-cellulose. An activator separated from the enzyme. Further chromatography on Sephadex G-100 and G-200 showed that the latter consisted of two components. The smaller of these (mol wt is approximately equal to 35 000) possessed enzyme transfer activity but the larger one (mol wt 80 000-90 000) required the addition of activator before any enzyme transfer activity was demonstrable. The activator itself was devoid of transfer activity. After chromatography of crude extracts of asparaginyl-tRNA synthetase on Sepharose 4B the activity in the enzyme peak, which was of considerably larger molecular weight than any of the fractions found after purification could be enhanced by addition of the activator. None of the fractions of the enzyme or of activator catalysed any extensive asparagine-dependent ATP-PP-i exchange, either in the presence or the absence of added tRNA."} {"id": "PMID:164949", "title": "Deoxyribonucleotide metabolism in Herpes simplex virus infected HeLa cells.", "content": "The effect of Rolly No. 11 strain herpes simplex virus infection of HeLa cells in culture on deoxynucleotide metabolism and the level of various enzymes concerned with the biosynthesis of DNA has been investigated. Of 18 enzyme activities studied, thymidine kinase, DNA polymerase and deoxyribonuclease were markedly augmented, a finding in agreement with previous reports. Deoxycytidine kinase, ribonucleotide reductase, thymidylate kinase and deoxycytidylate deaminase activities, in contrast with previous reports, did not increase; the activities of the other enzymes studied, also did not increase. Whereas most of the radioactivity derived from [14-C] thymidine in the acid-soluble fraction of the uninfected cells was present as deoxythymidine triphosphate, that present in the infected cells was primarily in the form of deoxythymidine monophosphate. Thus, in the infected cell deoxythymidylate kinase is a rate-limiting enzyme in the biosynthesis of deoxythymidine triphosphate. A marked increase in the pools of the four naturally occurring deoxynucleoside triphosphates (dTTP, dCTP, dATP, dGTP) was found. The rate of formation of the virus-induced enzymes was determined, as were the various nucleoside triphosphate pools and the other phosphorylated derivatives of thymidine; a maximum was reached for all these csmponents between 6 to 8 h post infection. Although an apparent greater synthesis of DNA occurred in the uninefected cells, when the specific activity of the radioactive deoxythymidine triphosphate was taken into account, there was actually a greater rate of DNA synthesis in the infected cells, with the peak at 8 h post infection.", "contents": "Deoxyribonucleotide metabolism in Herpes simplex virus infected HeLa cells. The effect of Rolly No. 11 strain herpes simplex virus infection of HeLa cells in culture on deoxynucleotide metabolism and the level of various enzymes concerned with the biosynthesis of DNA has been investigated. Of 18 enzyme activities studied, thymidine kinase, DNA polymerase and deoxyribonuclease were markedly augmented, a finding in agreement with previous reports. Deoxycytidine kinase, ribonucleotide reductase, thymidylate kinase and deoxycytidylate deaminase activities, in contrast with previous reports, did not increase; the activities of the other enzymes studied, also did not increase. Whereas most of the radioactivity derived from [14-C] thymidine in the acid-soluble fraction of the uninfected cells was present as deoxythymidine triphosphate, that present in the infected cells was primarily in the form of deoxythymidine monophosphate. Thus, in the infected cell deoxythymidylate kinase is a rate-limiting enzyme in the biosynthesis of deoxythymidine triphosphate. A marked increase in the pools of the four naturally occurring deoxynucleoside triphosphates (dTTP, dCTP, dATP, dGTP) was found. The rate of formation of the virus-induced enzymes was determined, as were the various nucleoside triphosphate pools and the other phosphorylated derivatives of thymidine; a maximum was reached for all these csmponents between 6 to 8 h post infection. Although an apparent greater synthesis of DNA occurred in the uninefected cells, when the specific activity of the radioactive deoxythymidine triphosphate was taken into account, there was actually a greater rate of DNA synthesis in the infected cells, with the peak at 8 h post infection."} {"id": "PMID:164950", "title": "Difference in the action of ethyl and methyl methane sulfonates on DNA template activity for RNA synthesis in vitro.", "content": "RNA produced in vitro from alkylated T7 DNA has been characterized by polyacrylamide gel electrophoresis. Methylation of T7 DNA by methyl methane sulfonate reduces RNA chain length. In contrast, ethylation of T7 DNA by ethyl methane sulfonate, while reducing RNA synthesis to the same extent, does not alter chain length.", "contents": "Difference in the action of ethyl and methyl methane sulfonates on DNA template activity for RNA synthesis in vitro. RNA produced in vitro from alkylated T7 DNA has been characterized by polyacrylamide gel electrophoresis. Methylation of T7 DNA by methyl methane sulfonate reduces RNA chain length. In contrast, ethylation of T7 DNA by ethyl methane sulfonate, while reducing RNA synthesis to the same extent, does not alter chain length."} {"id": "PMID:164951", "title": "A transfer RNA-dependent protein synthesizing system from Ehrlich ascites extracts.", "content": "An homologous cell-free system from Ehrlich ascites cells was made tRNA dependent by passing both the ribosomes and the ammonium sulfate fraction through DEAE-cellulose columns in 0.30 M KCl. Protein synthesis was routinely stimulated 20-50 fold by the addition of 100 mug/ml of ascites cell tRNA in the presence of oviduct mRNA, ascites mRNA, or encephalomyocarditis RNA.", "contents": "A transfer RNA-dependent protein synthesizing system from Ehrlich ascites extracts. An homologous cell-free system from Ehrlich ascites cells was made tRNA dependent by passing both the ribosomes and the ammonium sulfate fraction through DEAE-cellulose columns in 0.30 M KCl. Protein synthesis was routinely stimulated 20-50 fold by the addition of 100 mug/ml of ascites cell tRNA in the presence of oviduct mRNA, ascites mRNA, or encephalomyocarditis RNA."} {"id": "PMID:164952", "title": "Control of platelet glycogenolysis; Activation of phosphorylase kinase by calcium.", "content": "An apparent enigma during platelet aggregation is that increased glycogenolysis occurs despite a fall in cyclic AMP levels; Activation by a classical cascade is therefore unlikely, and an alternative stimulus for phosphorylase a formation was sought. It was found that low levels of Ca-2+ markedly activate phosphorylase b kinase from human platelets, with a Ka of 0i muM Ca-2+, which is similar to that for the skeletal muscle enzyme; The kinase activity is unstable, and on enzyme ageing is a 50% loss in activity with the Ka decreasing to 0.33 muM Ca-2+. In unstilulated platelets, phosphorylase a was 13.3% of toal measured activity, and glycogen synthetase I was 32.3%. Aggregation induced by ADP did not change the percentage of I synthetase, while increasing that for phosphorylase a. Dibutyryl cyclic AMP did, as expected, increase the percentage of both phosphorylated enzymes; These findings suggest that the natural activator of platelet glycogenolysis during aggregation is Ca-2+, which directly stimulates phosphorylase b kinase without altering glycogen synthetase activity. The cyclic AMP-dependent protein kinase does not appear to be involved;", "contents": "Control of platelet glycogenolysis; Activation of phosphorylase kinase by calcium. An apparent enigma during platelet aggregation is that increased glycogenolysis occurs despite a fall in cyclic AMP levels; Activation by a classical cascade is therefore unlikely, and an alternative stimulus for phosphorylase a formation was sought. It was found that low levels of Ca-2+ markedly activate phosphorylase b kinase from human platelets, with a Ka of 0i muM Ca-2+, which is similar to that for the skeletal muscle enzyme; The kinase activity is unstable, and on enzyme ageing is a 50% loss in activity with the Ka decreasing to 0.33 muM Ca-2+. In unstilulated platelets, phosphorylase a was 13.3% of toal measured activity, and glycogen synthetase I was 32.3%. Aggregation induced by ADP did not change the percentage of I synthetase, while increasing that for phosphorylase a. Dibutyryl cyclic AMP did, as expected, increase the percentage of both phosphorylated enzymes; These findings suggest that the natural activator of platelet glycogenolysis during aggregation is Ca-2+, which directly stimulates phosphorylase b kinase without altering glycogen synthetase activity. The cyclic AMP-dependent protein kinase does not appear to be involved;"} {"id": "PMID:164953", "title": "A quantitative assay for concanavalin A- and Ricinus communis agglutinin-mediated agglutinations of rat ascites hepatoma cells. Relationship between concanavalin A binding and cell agglutination.", "content": "A simple quantitative assay method was developed for the agglutination of rat ascites hepatoma cells mediated by Concanavalin A or Ricinus communis agglutinin. This method was based on the principle that the turbidity of a cell suspension is proportional to the sum of the cross-sectional area of cells and aggregatesmas predicted by the theoretical consideration, the turbidity decreased when cells were aggregated and the decrease was a function of the average number of the cells in aggregates. The agglutinability of the cells, judged by this method, showed a maximum value at a certain concentration of the agglutinin. By further addition of the agglutinin, the agglutinability slightly decreased from the maximum. These phenomena were observed both for Concanavalin A and Ricinus communis agglutinin. The binding and the agglutination experiments using [3-H]concanavalin A revealed that the binding to approx;0% of the total receptors caused a maximal agglutination. This suggested that the receptors responsible for the agglutination constitute only a small part of the total receptors on the surface.", "contents": "A quantitative assay for concanavalin A- and Ricinus communis agglutinin-mediated agglutinations of rat ascites hepatoma cells. Relationship between concanavalin A binding and cell agglutination. A simple quantitative assay method was developed for the agglutination of rat ascites hepatoma cells mediated by Concanavalin A or Ricinus communis agglutinin. This method was based on the principle that the turbidity of a cell suspension is proportional to the sum of the cross-sectional area of cells and aggregatesmas predicted by the theoretical consideration, the turbidity decreased when cells were aggregated and the decrease was a function of the average number of the cells in aggregates. The agglutinability of the cells, judged by this method, showed a maximum value at a certain concentration of the agglutinin. By further addition of the agglutinin, the agglutinability slightly decreased from the maximum. These phenomena were observed both for Concanavalin A and Ricinus communis agglutinin. The binding and the agglutination experiments using [3-H]concanavalin A revealed that the binding to approx;0% of the total receptors caused a maximal agglutination. This suggested that the receptors responsible for the agglutination constitute only a small part of the total receptors on the surface."} {"id": "PMID:164954", "title": "ESR study of aqueous dispersions of beta-lactoglobulin and spin-labelled glyceryl monostearate.", "content": "From the ESR spectra of aqueous dispersions of synthetic glyceryl monostearate (spin labelled at C-12) a critical micelle concentration of 30 mumol/l at room temperature was obtained, which agrees with that deduced from surface tension measurements. At monoglyceride concentrations smaller or larger than the critical micelle concentration, the monomers show increased motional restriction with increasing molar ratio of beta-lactoglobulin to monoglyceride up to a value of 10, as determined from calculated rotational correlation times; A similar progressive interaction was deduced from spectral changes observed on equimolar dispersions of beta-lactoglobulin and monoglyceride on raising the temperature to 55 degrees C at which the protein and monoglyceride coprecipitate. The relevance of these finding for non-labelled monoglyceride dispersions is indicated by the similarity of the pH-dependent flocculation behaviour of labelled and non-labelled monoglycerides, both in the absence and presence of beta-lactoglobulin; In addition, proton magnetic resonance and mechanical stability measurements suggest that spin-labelled glyceryl monosterate behaves analogously to non-labelled glyceryl monooleate.", "contents": "ESR study of aqueous dispersions of beta-lactoglobulin and spin-labelled glyceryl monostearate. From the ESR spectra of aqueous dispersions of synthetic glyceryl monostearate (spin labelled at C-12) a critical micelle concentration of 30 mumol/l at room temperature was obtained, which agrees with that deduced from surface tension measurements. At monoglyceride concentrations smaller or larger than the critical micelle concentration, the monomers show increased motional restriction with increasing molar ratio of beta-lactoglobulin to monoglyceride up to a value of 10, as determined from calculated rotational correlation times; A similar progressive interaction was deduced from spectral changes observed on equimolar dispersions of beta-lactoglobulin and monoglyceride on raising the temperature to 55 degrees C at which the protein and monoglyceride coprecipitate. The relevance of these finding for non-labelled monoglyceride dispersions is indicated by the similarity of the pH-dependent flocculation behaviour of labelled and non-labelled monoglycerides, both in the absence and presence of beta-lactoglobulin; In addition, proton magnetic resonance and mechanical stability measurements suggest that spin-labelled glyceryl monosterate behaves analogously to non-labelled glyceryl monooleate."} {"id": "PMID:164955", "title": "Inhibition by cyclic AMP of lactose production in lactating guinea pig mammary gland slices.", "content": "Addition of the cyclic AMP phosphodiesterase inhibitors theophylline (10- minus 2 M) or papaverine (10- minus 4 M) leads to a complete inhibition of lactose synthesis in incubated guinea pig mammary gland slices. Addition of 10- minus 5 M cyclic AMP or dibutyryl cyclic AMP results in 1 30-40% inhibition of the synthesis, which effect is not increased by applying higher concentrations of these compounds. A 30-40% inhibition can also be obtained with epinephrine (5 - 10- minus 5 M), or isoproterenol (10- minus 4 M), but the polypeptide hormones glucagon (10- minus 7 M), insulin (1 munit/ml) and relaxin (10 mug/ml) do not significantly affect lactose synthesis. Cytochalasin B (5 mug/ml) inhibits lactose production by 58and colchicine (10- minus 5 M) by 25%. These experiments suggest that an increase in the intracellular level of cyclic AMP either through its addition, through hormonal stimulation of its synthesis, or through inhibition of its intracellular breakdown, leads to an inhibition of lactose production in lactating mammary gland. This effect of cyclic AMP is similar to that of progesterone, which is known to inhibit lactation in vivo and the withdrawal of which at parturition has been postulated to initiate lactogenesis.", "contents": "Inhibition by cyclic AMP of lactose production in lactating guinea pig mammary gland slices. Addition of the cyclic AMP phosphodiesterase inhibitors theophylline (10- minus 2 M) or papaverine (10- minus 4 M) leads to a complete inhibition of lactose synthesis in incubated guinea pig mammary gland slices. Addition of 10- minus 5 M cyclic AMP or dibutyryl cyclic AMP results in 1 30-40% inhibition of the synthesis, which effect is not increased by applying higher concentrations of these compounds. A 30-40% inhibition can also be obtained with epinephrine (5 - 10- minus 5 M), or isoproterenol (10- minus 4 M), but the polypeptide hormones glucagon (10- minus 7 M), insulin (1 munit/ml) and relaxin (10 mug/ml) do not significantly affect lactose synthesis. Cytochalasin B (5 mug/ml) inhibits lactose production by 58and colchicine (10- minus 5 M) by 25%. These experiments suggest that an increase in the intracellular level of cyclic AMP either through its addition, through hormonal stimulation of its synthesis, or through inhibition of its intracellular breakdown, leads to an inhibition of lactose production in lactating mammary gland. This effect of cyclic AMP is similar to that of progesterone, which is known to inhibit lactation in vivo and the withdrawal of which at parturition has been postulated to initiate lactogenesis."} {"id": "PMID:164956", "title": "Adenosine 3'5'-m onophosphate dependent phosphorylation of ribosomes and ribosomal subunits from bovine corpus luteum.", "content": "In a previous publication the purification and properties of two protein kinases (KI and KII) from a soluble fraction of bovine corpus luteum and the stimulation of the latter fol. Chem. 248,494-501). We have now studied the effects oc cyclic AMP and luteinizing hormone on ribosomal protein phosphorylation of corpus luteum by protein kinase II. Protein kinase II catalyzed the phosphorylation of ribosomes by transfer of terminal phosphate of ATP to ribosomal proteinsmextraction with hot trichloroacetic acid and non-aqueous solvent revealed that about 80% of total radioactivity incorporated remain associated with the protein residue. Radioactivity was identified in the phosphoserine and phosphothreonine residues of polypeptides by high voltage paper electrophoresis; The extent of phosphorylation was stimulated by cyclic AMP but not by luteinizing hormonemat least 9 proteins of 80-S ribosomes and 12 proteins of the 60-S ribosomal subunit were phosphorylated in the presence of cyclic AMP as resolved by urea polyacrylamide gel electrophoresis. However, only one major and four minor bands were phosphorylated in the ase of 40-S ribosomal subunit under the influence of cyclic AMP. The ribosomal protein phosphorylation catalyzed by protein kinase II is regulated by cyclic AMP wherease luteinizing hormone has no effect on ribosome phosphorylation.", "contents": "Adenosine 3'5'-m onophosphate dependent phosphorylation of ribosomes and ribosomal subunits from bovine corpus luteum. In a previous publication the purification and properties of two protein kinases (KI and KII) from a soluble fraction of bovine corpus luteum and the stimulation of the latter fol. Chem. 248,494-501). We have now studied the effects oc cyclic AMP and luteinizing hormone on ribosomal protein phosphorylation of corpus luteum by protein kinase II. Protein kinase II catalyzed the phosphorylation of ribosomes by transfer of terminal phosphate of ATP to ribosomal proteinsmextraction with hot trichloroacetic acid and non-aqueous solvent revealed that about 80% of total radioactivity incorporated remain associated with the protein residue. Radioactivity was identified in the phosphoserine and phosphothreonine residues of polypeptides by high voltage paper electrophoresis; The extent of phosphorylation was stimulated by cyclic AMP but not by luteinizing hormonemat least 9 proteins of 80-S ribosomes and 12 proteins of the 60-S ribosomal subunit were phosphorylated in the presence of cyclic AMP as resolved by urea polyacrylamide gel electrophoresis. However, only one major and four minor bands were phosphorylated in the ase of 40-S ribosomal subunit under the influence of cyclic AMP. The ribosomal protein phosphorylation catalyzed by protein kinase II is regulated by cyclic AMP wherease luteinizing hormone has no effect on ribosome phosphorylation."} {"id": "PMID:164957", "title": "Effect of adrenergic agents on alpha-amylase release and adenosine 3',5'-monophosphate accumulation in rat parotid tissue slices.", "content": "The role of cyclic AMP in stimulus-secretion coupling with investigated in rat parotid tissue slices in vitro. Isoproterenol and norepinephrine stimulated a rapid intracellular accumulation of cyclic AMP, which reached a maximum level of 20-30 times the control value by 5 to 10 min after addition of the drug. Isoproterenol was approximately ten times more potent in stimulating both alpha-amylase release and cyclic AMP accumulation than were norepinephrine and epinephrine, which had nearly equal effects on these two parameters. Salbutamol and phenylephrine were less effectivema parallel order of potency and sensitivity was observed for the stimulation of adenylate cyclase activity in a washed particulate fractionmthe results suggest that these drugs are acting on a parotid acinar cell through a beta1-adrenergic mechanismmat the lowest concentrations tested, each of the adrenergic agonists stimulated significant alpha-anylase release with no detectable stimulation of cyclic AMP accumulationmeven in the presence of theophylline, phenylephrine at several concentrations increased alpha-amylase release without a detectable increase in cyclic AMP levels. However, phenylephrine did stimulate adenylate cyclase. These data suggest that, under certain conditions, large increases in the intra-cellular concentration of cyclic AMP may not be necessary for stimulation of alpha-amylase release by adrenergic agonists. Also consistent with this idea was the observation that stimulation of cyclic AMP accumulation by isoproterenol was much more sensitive to inhibition by propranolol than was the stimulation of alpha-amylase release by isoproterenol. Stimulation of alpha-amylase release by phenylephrine was only partially blocked by either alpha- or beta-adrenergic blocking agents, whereas stimulation of adenylate cyclase by phenylephrine was blocked by propranolol and not by phentolaminemphenoxybenzamine and phentolamine potentiated the effects of norepinephrine and isoproterenol on both cyclic AMP accumulation and alpha-amylase release by N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate; These observations may indicate a non-specific action of phenoxybenzamine, and demonstrate the need for caution in interpreting evidence obtained using alpha-adrenergic blocking agents as tools for investigation of alpha- and beta-adrenergic antagonism.", "contents": "Effect of adrenergic agents on alpha-amylase release and adenosine 3',5'-monophosphate accumulation in rat parotid tissue slices. The role of cyclic AMP in stimulus-secretion coupling with investigated in rat parotid tissue slices in vitro. Isoproterenol and norepinephrine stimulated a rapid intracellular accumulation of cyclic AMP, which reached a maximum level of 20-30 times the control value by 5 to 10 min after addition of the drug. Isoproterenol was approximately ten times more potent in stimulating both alpha-amylase release and cyclic AMP accumulation than were norepinephrine and epinephrine, which had nearly equal effects on these two parameters. Salbutamol and phenylephrine were less effectivema parallel order of potency and sensitivity was observed for the stimulation of adenylate cyclase activity in a washed particulate fractionmthe results suggest that these drugs are acting on a parotid acinar cell through a beta1-adrenergic mechanismmat the lowest concentrations tested, each of the adrenergic agonists stimulated significant alpha-anylase release with no detectable stimulation of cyclic AMP accumulationmeven in the presence of theophylline, phenylephrine at several concentrations increased alpha-amylase release without a detectable increase in cyclic AMP levels. However, phenylephrine did stimulate adenylate cyclase. These data suggest that, under certain conditions, large increases in the intra-cellular concentration of cyclic AMP may not be necessary for stimulation of alpha-amylase release by adrenergic agonists. Also consistent with this idea was the observation that stimulation of cyclic AMP accumulation by isoproterenol was much more sensitive to inhibition by propranolol than was the stimulation of alpha-amylase release by isoproterenol. Stimulation of alpha-amylase release by phenylephrine was only partially blocked by either alpha- or beta-adrenergic blocking agents, whereas stimulation of adenylate cyclase by phenylephrine was blocked by propranolol and not by phentolaminemphenoxybenzamine and phentolamine potentiated the effects of norepinephrine and isoproterenol on both cyclic AMP accumulation and alpha-amylase release by N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate; These observations may indicate a non-specific action of phenoxybenzamine, and demonstrate the need for caution in interpreting evidence obtained using alpha-adrenergic blocking agents as tools for investigation of alpha- and beta-adrenergic antagonism."} {"id": "PMID:164958", "title": "Selenium - induced redistribution of cadmium binding to tissue proteins: a possible mechanism of protection against cadmium toxicity.", "content": "The mechanisms involved in the protection by Se against Cd toxicity in the rat were investigated. Se was found to significantly increase the Cd content in the blood and the testis, while decreasing that in the liver and kidney. Se diverted almost all the Cd in the soluble fraction of the testis from low-molecular-weight (MW) proteins to larger ones. Since the soluble fraction was the major subcellular Cd-binding component, the diversion of Cd by Se appears to be a mechanism involved in the protection by this element against the Cd-induced testicular injury. The diversion in binding of the Cd in the soluble fraction to higher MW proteins was also observed in the kidney and liver, and may be a second mechanism involved in the protection of these organs against Cd by Se, in addition to the reductive effect of Se on the tissue Cd concentration. Se was also found in these higher MW Cd-binding proteins. Based on a similarity of MW of about 115,000, the Cd-binding, Se-containing proteins found in these organs appear to be similar. A diversion of Cd from lower MW proteins to larger ones by Se was also found in the plasma, but the Cd-binding, Se-containing proteins in plasma appear to be different from those found in the other organs since they have a larger MW.", "contents": "Selenium - induced redistribution of cadmium binding to tissue proteins: a possible mechanism of protection against cadmium toxicity. The mechanisms involved in the protection by Se against Cd toxicity in the rat were investigated. Se was found to significantly increase the Cd content in the blood and the testis, while decreasing that in the liver and kidney. Se diverted almost all the Cd in the soluble fraction of the testis from low-molecular-weight (MW) proteins to larger ones. Since the soluble fraction was the major subcellular Cd-binding component, the diversion of Cd by Se appears to be a mechanism involved in the protection by this element against the Cd-induced testicular injury. The diversion in binding of the Cd in the soluble fraction to higher MW proteins was also observed in the kidney and liver, and may be a second mechanism involved in the protection of these organs against Cd by Se, in addition to the reductive effect of Se on the tissue Cd concentration. Se was also found in these higher MW Cd-binding proteins. Based on a similarity of MW of about 115,000, the Cd-binding, Se-containing proteins found in these organs appear to be similar. A diversion of Cd from lower MW proteins to larger ones by Se was also found in the plasma, but the Cd-binding, Se-containing proteins in plasma appear to be different from those found in the other organs since they have a larger MW."} {"id": "PMID:164961", "title": "Effects of sulfhydryl reagents on basal and vasopressin-stimulated Na+ transport in the toad bladder.", "content": "The role of reactive SH groups (presumably in proteins) of the apical plasma membrane in transepithelial Na+ transport was studied in the isolated urinary bladder of the toad. On the basis of assays for TCA-soluble SH compounds (e.g., glutathione, methionine), PCMB, PCMPS, NTCB, and DTNB did not penetrate the intracellular compartment from the luminal media either in control or vasopressin-treated bladders. In contrast, PCMB from the serosal side and NEM from the luminal side titrated significant fractions of the TCA-soluble SH compounds. We conclude, therefore, the PCMB, PCMPS, NTCB, and DTNB are suitable reagents for studies on the physiological properties of apical plasma membrane SH groups. Titration of apical membrane SH groups with PCMPS, NTCB, and DTNB revealed heterogeneity in functional responses: PCMPS and NTCB elicited transient, 25-60% increases in SCC. In substrate-free media, pretreatment with these reagents inhibited the increase in SCC produced by vasopressin or cyclic AMP (+ theophylline). In glucose-enriched media, the responses to combinations of vasopressin and PCMPS or NTCB were additive, implying activation via parallel pathways. Simultaneous addition of vasopressin or cyclic AMP (+ theophylline) and NTCB resulted in marked synergism, presumably as a result of unmasking of SH groups by the the hormone (or the intermediate). These results suggest that basal Na+ transport is regulated in part by SH compounds in the apical membrane that are distinct, although not necessarily different in kind, from those involved in the response to vasopressin.", "contents": "Effects of sulfhydryl reagents on basal and vasopressin-stimulated Na+ transport in the toad bladder. The role of reactive SH groups (presumably in proteins) of the apical plasma membrane in transepithelial Na+ transport was studied in the isolated urinary bladder of the toad. On the basis of assays for TCA-soluble SH compounds (e.g., glutathione, methionine), PCMB, PCMPS, NTCB, and DTNB did not penetrate the intracellular compartment from the luminal media either in control or vasopressin-treated bladders. In contrast, PCMB from the serosal side and NEM from the luminal side titrated significant fractions of the TCA-soluble SH compounds. We conclude, therefore, the PCMB, PCMPS, NTCB, and DTNB are suitable reagents for studies on the physiological properties of apical plasma membrane SH groups. Titration of apical membrane SH groups with PCMPS, NTCB, and DTNB revealed heterogeneity in functional responses: PCMPS and NTCB elicited transient, 25-60% increases in SCC. In substrate-free media, pretreatment with these reagents inhibited the increase in SCC produced by vasopressin or cyclic AMP (+ theophylline). In glucose-enriched media, the responses to combinations of vasopressin and PCMPS or NTCB were additive, implying activation via parallel pathways. Simultaneous addition of vasopressin or cyclic AMP (+ theophylline) and NTCB resulted in marked synergism, presumably as a result of unmasking of SH groups by the the hormone (or the intermediate). These results suggest that basal Na+ transport is regulated in part by SH compounds in the apical membrane that are distinct, although not necessarily different in kind, from those involved in the response to vasopressin."} {"id": "PMID:164962", "title": "Co-ordination behaviour of nucleic acid bases against the Fe(I)(NO)-2 group in solution. I. Purines: ESR study.", "content": "The binding sites of purine bases in the presence of the Fe(I)(NO)-2 group were investigated on the basis of the nuclear hyperfine structure of the electron spin resonance spectra. Selective isotopic substitution with 15-NO was used to clarify co-ordindination. Coupling constants and different types of complexes were determined by means of computer-simulated ESR spectra. Comparison was made with the binding sites of nucleotides and it was concluded that N-7, in the imidazole ring, is the preferred binding site. A structure with two base molecules bonded to the iron atom was proposed. Finally 8-azaguanine, an antitumoral agent, was studied and the special behaviour of this antimetabolite was demonstrated in the biologically-interesting pH values.", "contents": "Co-ordination behaviour of nucleic acid bases against the Fe(I)(NO)-2 group in solution. I. Purines: ESR study. The binding sites of purine bases in the presence of the Fe(I)(NO)-2 group were investigated on the basis of the nuclear hyperfine structure of the electron spin resonance spectra. Selective isotopic substitution with 15-NO was used to clarify co-ordindination. Coupling constants and different types of complexes were determined by means of computer-simulated ESR spectra. Comparison was made with the binding sites of nucleotides and it was concluded that N-7, in the imidazole ring, is the preferred binding site. A structure with two base molecules bonded to the iron atom was proposed. Finally 8-azaguanine, an antitumoral agent, was studied and the special behaviour of this antimetabolite was demonstrated in the biologically-interesting pH values."} {"id": "PMID:164963", "title": "[Phospholipid composition of synaptosomes from the brains of normal rabbits and rabbits poisoned with phospho-organic cholinesterase inhibitors].", "content": "The authors studied quantitative and qualitative composition of phospholipids isolated by fractionation in the sucrose density gradient. The diacyl-aminophospholipid (APL) content of synaptosomes was lower than that of the brain homogenates. On the other hand, the plasmologen APL, phosphoinositide and phosphatidylcholine content was greater in the synaptosomes. Strong excitation of the CNS induced with organo phosphorus inhibitors resulted in a 25% decrease of diacyl APL contnet and a 17% elevation of plasmalogen APL content in the whole brain homogenate. The phospholipid composition of synaptosomes remained unchanged, however.", "contents": "[Phospholipid composition of synaptosomes from the brains of normal rabbits and rabbits poisoned with phospho-organic cholinesterase inhibitors]. The authors studied quantitative and qualitative composition of phospholipids isolated by fractionation in the sucrose density gradient. The diacyl-aminophospholipid (APL) content of synaptosomes was lower than that of the brain homogenates. On the other hand, the plasmologen APL, phosphoinositide and phosphatidylcholine content was greater in the synaptosomes. Strong excitation of the CNS induced with organo phosphorus inhibitors resulted in a 25% decrease of diacyl APL contnet and a 17% elevation of plasmalogen APL content in the whole brain homogenate. The phospholipid composition of synaptosomes remained unchanged, however."} {"id": "PMID:164964", "title": "[The effect of ethymizole on the concentration of cyclic 3',5'-adenosine monophosphate in brain tissue].", "content": "It was found by the enzymatic method of cAMP determination that aethymizol (25 mg/kg) caused a more than double increase in cAMP in the rat brain tissue 20 minutes after the intraperitoneal injection. Changes in carbohydrate metabolism in the brain typical of cAMP increased, i.e. reduction in glycogen and an increase in glucose were revealed. The mechanism of aethymizol action was apparently connected with an increase in cAMP formation in the brain tissue.", "contents": "[The effect of ethymizole on the concentration of cyclic 3',5'-adenosine monophosphate in brain tissue]. It was found by the enzymatic method of cAMP determination that aethymizol (25 mg/kg) caused a more than double increase in cAMP in the rat brain tissue 20 minutes after the intraperitoneal injection. Changes in carbohydrate metabolism in the brain typical of cAMP increased, i.e. reduction in glycogen and an increase in glucose were revealed. The mechanism of aethymizol action was apparently connected with an increase in cAMP formation in the brain tissue."} {"id": "PMID:164965", "title": "Effects of anaerobiosis and inhibitors on O2-production by human granulocytes.", "content": "A study was carried out on the effect of a number of inhibitors as well as of anaerobiosis on the production of superoxide (O2 minus) by human granulocytes. Several metabolic inhibitors, including bazide, cyanide, antimycin A, and 2,4-dinitrophenol had no effect on O2 minus production. Methimazole, which inhibits myeloperoxidase, was also without effect. The sulfhydryl reagents N-ethylmalemide and iodoacetamide greatly inhibited O2 minus production. O2 minus production did not take place under N2. Agents that affect cell motility were also examined. Colchicine and vinblastine, alkaloids which affect microtubule function, had little effect on granulycote O2 minus production. On the other hand, cytochalasin B, a fungal antimetabolite thought to affect microfilaments, inhibited O2 minus production by resting granulocytes and stimulated its production by cells incubated with bacteria. The mechanism and significance of this effect remain to be elucidated.", "contents": "Effects of anaerobiosis and inhibitors on O2-production by human granulocytes. A study was carried out on the effect of a number of inhibitors as well as of anaerobiosis on the production of superoxide (O2 minus) by human granulocytes. Several metabolic inhibitors, including bazide, cyanide, antimycin A, and 2,4-dinitrophenol had no effect on O2 minus production. Methimazole, which inhibits myeloperoxidase, was also without effect. The sulfhydryl reagents N-ethylmalemide and iodoacetamide greatly inhibited O2 minus production. O2 minus production did not take place under N2. Agents that affect cell motility were also examined. Colchicine and vinblastine, alkaloids which affect microtubule function, had little effect on granulycote O2 minus production. On the other hand, cytochalasin B, a fungal antimetabolite thought to affect microfilaments, inhibited O2 minus production by resting granulocytes and stimulated its production by cells incubated with bacteria. The mechanism and significance of this effect remain to be elucidated."} {"id": "PMID:164966", "title": "The estimation of 3,4-dihydroxyphenylacetic acid, homovanillic acid and homo-isovanillic acid in nervous tissue by gas-liquid chromatography and electron capture detection.", "content": "1 A gas chromatographic method using electron capture detection is described for the estimation of three acidic metabolites of dopamine, 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-hydroxy-4-methoxyphenylacetic acid (homo-isovanillic acid, iso-HVA). The method is based on the formation of the trifluoroacetyl-hexafluoroisopropyl derivatives of the three acids. 2 The method has been applied to the estimation of DOPAC, HVA and iso-HVA in tissues from the central and peripheral nervous systems.", "contents": "The estimation of 3,4-dihydroxyphenylacetic acid, homovanillic acid and homo-isovanillic acid in nervous tissue by gas-liquid chromatography and electron capture detection. 1 A gas chromatographic method using electron capture detection is described for the estimation of three acidic metabolites of dopamine, 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-hydroxy-4-methoxyphenylacetic acid (homo-isovanillic acid, iso-HVA). The method is based on the formation of the trifluoroacetyl-hexafluoroisopropyl derivatives of the three acids. 2 The method has been applied to the estimation of DOPAC, HVA and iso-HVA in tissues from the central and peripheral nervous systems."} {"id": "PMID:164967", "title": "Possible role of a beta-adrenoceptor in the regulation of noradrenaline release by nerve stimulation through a positive feed-back mechanism.", "content": "1 The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea-pig isolated atria. 2 Isoprenaline (1.2 times 10-minus 8M) increased while propranolol (1.0 times 10-minus 7M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 times 10-minus 6M), which increased by approximately three-fold the overflow of [3H]-noradrenaline elicited by nerve stimulation. 3 Neuronal accumulation of tritiated noradrenaline in guinea-pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentration employed in this study. 4 Isoprenaline (1.2 times 10-minus 8M) induced a positive chronotropic effect of about 80 percent of the maximum. On the other hand, propranolol produced a shift to the right in the frequency-response curve to nerve stimulation and in the concentration-response curve to exogenous noradrenaline in guinea-pig atria. 5 In the isolated nictitating membrane of the cat, the frequency-response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 times 10-minus 6M of N,-2-(2,6-dimethylphenoxy)propyl-N,N,N-trimethylammonium (beta-methyl-TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor beta-methyl-TM 10 affected responses to exogenous noradrenaline. 6. The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed-back mechanism for noradrenaline release by nerve stimulation mediated via alpha-adrenoceptors a positive feed-back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic beta-adrenoceptors.", "contents": "Possible role of a beta-adrenoceptor in the regulation of noradrenaline release by nerve stimulation through a positive feed-back mechanism. 1 The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea-pig isolated atria. 2 Isoprenaline (1.2 times 10-minus 8M) increased while propranolol (1.0 times 10-minus 7M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 times 10-minus 6M), which increased by approximately three-fold the overflow of [3H]-noradrenaline elicited by nerve stimulation. 3 Neuronal accumulation of tritiated noradrenaline in guinea-pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentration employed in this study. 4 Isoprenaline (1.2 times 10-minus 8M) induced a positive chronotropic effect of about 80 percent of the maximum. On the other hand, propranolol produced a shift to the right in the frequency-response curve to nerve stimulation and in the concentration-response curve to exogenous noradrenaline in guinea-pig atria. 5 In the isolated nictitating membrane of the cat, the frequency-response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 times 10-minus 6M of N,-2-(2,6-dimethylphenoxy)propyl-N,N,N-trimethylammonium (beta-methyl-TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor beta-methyl-TM 10 affected responses to exogenous noradrenaline. 6. The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed-back mechanism for noradrenaline release by nerve stimulation mediated via alpha-adrenoceptors a positive feed-back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic beta-adrenoceptors."} {"id": "PMID:164968", "title": "Two types of insomnia: too much waking or not enough sleep.", "content": "The stability of sleep was examined in two kinds of induced insomnia, namely after caffeine administration and after hypnotic drug withdrawal. The duration of each episode of any one sleep stage or any episode of intervening wakefulness plus drowsiness was determined. After caffeine there was an increase in longer episodes of intervening wakefulness plus drowsiness, but no significant change in the episode duration of any of the sleep stages. In the case of drug withdrawal there was no change in the episode duration of intervening wakefulness plus drowsiness, but there was a significant shortening of episode duration in sleep stages 2 and 3+4, with a similar trend for REM sleep episodes. Caffeine 'insomnia' thus seems characterized by increased stability of wakefulness, and hypnotic withdrawal 'insomnia' by decreased stability fo sleep. The type of analysis undertaken in this study could increase understanding of other types of insomnia.", "contents": "Two types of insomnia: too much waking or not enough sleep. The stability of sleep was examined in two kinds of induced insomnia, namely after caffeine administration and after hypnotic drug withdrawal. The duration of each episode of any one sleep stage or any episode of intervening wakefulness plus drowsiness was determined. After caffeine there was an increase in longer episodes of intervening wakefulness plus drowsiness, but no significant change in the episode duration of any of the sleep stages. In the case of drug withdrawal there was no change in the episode duration of intervening wakefulness plus drowsiness, but there was a significant shortening of episode duration in sleep stages 2 and 3+4, with a similar trend for REM sleep episodes. Caffeine 'insomnia' thus seems characterized by increased stability of wakefulness, and hypnotic withdrawal 'insomnia' by decreased stability fo sleep. The type of analysis undertaken in this study could increase understanding of other types of insomnia."} {"id": "PMID:164974", "title": "Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis.", "content": "Circulating levels of melanotrophic horomones and ACTH were determined in patients treated by maintenance dialysis for chronic renal failure. Plasma melanotrophic hormone levels were greatly increased in all patients studied (125-1100 ng/1 as compared with 12-36 ng/1 in normal adults) and were correlated with the duration of treatment. Skin pigmentation, especially in exposed areas, was notably increased, particularly in those patients with the highest plasma melanotrophic concentrations. Plasma ACTH levels were normal or only slightly raised and circulating corticosteroid concentrations, as determined by a fluorimetric method, all lay within the physiological range. The dissociation between ACTH and melanotrophic hormone levels in these patients may have been the result of a slower metabolic clearance of the latter.", "contents": "Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis. Circulating levels of melanotrophic horomones and ACTH were determined in patients treated by maintenance dialysis for chronic renal failure. Plasma melanotrophic hormone levels were greatly increased in all patients studied (125-1100 ng/1 as compared with 12-36 ng/1 in normal adults) and were correlated with the duration of treatment. Skin pigmentation, especially in exposed areas, was notably increased, particularly in those patients with the highest plasma melanotrophic concentrations. Plasma ACTH levels were normal or only slightly raised and circulating corticosteroid concentrations, as determined by a fluorimetric method, all lay within the physiological range. The dissociation between ACTH and melanotrophic hormone levels in these patients may have been the result of a slower metabolic clearance of the latter."} {"id": "PMID:164980", "title": "A comparison of the peptide composition of human serum low and very low density lipoprotein.", "content": "We have examined the apoprotein structure of human very low density lipoprotein (VLDL) and two subfractions of human low density lipoproteins, LDL-2 (d 1", "contents": "A comparison of the peptide composition of human serum low and very low density lipoprotein. We have examined the apoprotein structure of human very low density lipoprotein (VLDL) and two subfractions of human low density lipoproteins, LDL-2 (d 1"} {"id": "PMID:164981", "title": "Mammalian fatty acid synthetase. II. Modification of purified human liver complex activity.", "content": "Highly purified human-liver fatty acid synthetase complex was used to study the effect of several potential modifiers. Adenosine 3',5'-phosphate did not alter the activity of either purified synthetase or of multienzyme present in 700 times g supernates. Its dibutyryl derivative was also ineffective when incubated with liver slices. Fructose 1,6-diphosphate, fructose 6-phosphate, and glucose 6-phosphate stimulated significantly the activity of the purified enzyme. Fructose 1,6-diphosphate, which was most effective, decreased the Km of the synthetase for NADPH. Phosphoenolpyruvate, rac-glycero-3-phosphate and potassium phosphate were ineffective; All longg-chain fatty acyl-CoA thioesters tested were inhibitory, but this effect was not observed until the regions of their critical micellar concentrations were reached. Free myristate, palmitate, and stearate did not inhibit synthetase activity up to the highest concentration tested (1 mM)qn enzyme preparation derived from livers of fasted rats inactivated purified rat-liver 4'-phospho[14-C]pantetheine-fatty acid synthetase by releasing its prosthetic group. It also decreased the activity of the purified human-liver complex.", "contents": "Mammalian fatty acid synthetase. II. Modification of purified human liver complex activity. Highly purified human-liver fatty acid synthetase complex was used to study the effect of several potential modifiers. Adenosine 3',5'-phosphate did not alter the activity of either purified synthetase or of multienzyme present in 700 times g supernates. Its dibutyryl derivative was also ineffective when incubated with liver slices. Fructose 1,6-diphosphate, fructose 6-phosphate, and glucose 6-phosphate stimulated significantly the activity of the purified enzyme. Fructose 1,6-diphosphate, which was most effective, decreased the Km of the synthetase for NADPH. Phosphoenolpyruvate, rac-glycero-3-phosphate and potassium phosphate were ineffective; All longg-chain fatty acyl-CoA thioesters tested were inhibitory, but this effect was not observed until the regions of their critical micellar concentrations were reached. Free myristate, palmitate, and stearate did not inhibit synthetase activity up to the highest concentration tested (1 mM)qn enzyme preparation derived from livers of fasted rats inactivated purified rat-liver 4'-phospho[14-C]pantetheine-fatty acid synthetase by releasing its prosthetic group. It also decreased the activity of the purified human-liver complex."} {"id": "PMID:164982", "title": "Lysolecithin-cholesterol interaction. A spin-resonance and electron-micrographic study.", "content": "Another publication (rand, R. P., Pangborn, W., Purdon, A. D., and Tinker, D. O.(1975) Can. j. Biochem. 53, 189-195) has established that lysolecithin and cholesterol interact to form an equimolar complex. We have investigated this complex using the techniques of electron spin resonance (e.s.r) and electronmicroscopy. By varying the cholesterol concentration with lysolecithin in both thin films and dispersions studied by these techniques, we have observed the interaction between lysolecithin and equimolar complex below 50 mol % cholesterol, and between crystalline cholesterol and equimolar complex above 50 mol % cholesterol. We have observed an interesting alteration in morphology by electron microscopy, and an isotropic to anisotropic spectral change using 3-dosylcholestane and 12-doxylstearic acid spin-labelled probes when the cholesterol concentration is increased from 20 to 33 mol %. The equimolar complex is stable in the presence of crystalline cholesterol, and exhibits no phase changes in the physiological temperature range. Implications for membrane structure are discussed.", "contents": "Lysolecithin-cholesterol interaction. A spin-resonance and electron-micrographic study. Another publication (rand, R. P., Pangborn, W., Purdon, A. D., and Tinker, D. O.(1975) Can. j. Biochem. 53, 189-195) has established that lysolecithin and cholesterol interact to form an equimolar complex. We have investigated this complex using the techniques of electron spin resonance (e.s.r) and electronmicroscopy. By varying the cholesterol concentration with lysolecithin in both thin films and dispersions studied by these techniques, we have observed the interaction between lysolecithin and equimolar complex below 50 mol % cholesterol, and between crystalline cholesterol and equimolar complex above 50 mol % cholesterol. We have observed an interesting alteration in morphology by electron microscopy, and an isotropic to anisotropic spectral change using 3-dosylcholestane and 12-doxylstearic acid spin-labelled probes when the cholesterol concentration is increased from 20 to 33 mol %. The equimolar complex is stable in the presence of crystalline cholesterol, and exhibits no phase changes in the physiological temperature range. Implications for membrane structure are discussed."} {"id": "PMID:164983", "title": "Studies of the regulation of purine nucleotide catabolism.", "content": "Ehrlich ascites tumor cells containing radioactive ATP were incubated in vitro with a range of concentrations of 2-deoxyglucose in order to produce different rates of ATP catabolism. Concentrations of all radioactive products of ATP catabolism were measured, and apparent rates of adenylate deaminase and inosinate dehydrogenase and of adenylate and inosinate dephosphorylation were calculated. It was concluded that these processes were reggulated primarily by the rate of formation of substrate, and to a lesser extent in some cases, by substrate concentration. No evidence was obtained for regulation of these processes by the concentration of ATP. The deoxyglucose-induced catabolism of radioactive GTP was also studied. When ATP catabolism was induced by incubation with 2,4-dinitrophenol, time courses of accumulation of purine nucleoside monophosphates and rates of alternative pathways of their metabolism were quite different than when deoxyglucose was used.", "contents": "Studies of the regulation of purine nucleotide catabolism. Ehrlich ascites tumor cells containing radioactive ATP were incubated in vitro with a range of concentrations of 2-deoxyglucose in order to produce different rates of ATP catabolism. Concentrations of all radioactive products of ATP catabolism were measured, and apparent rates of adenylate deaminase and inosinate dehydrogenase and of adenylate and inosinate dephosphorylation were calculated. It was concluded that these processes were reggulated primarily by the rate of formation of substrate, and to a lesser extent in some cases, by substrate concentration. No evidence was obtained for regulation of these processes by the concentration of ATP. The deoxyglucose-induced catabolism of radioactive GTP was also studied. When ATP catabolism was induced by incubation with 2,4-dinitrophenol, time courses of accumulation of purine nucleoside monophosphates and rates of alternative pathways of their metabolism were quite different than when deoxyglucose was used."} {"id": "PMID:164984", "title": "Rat liver nuclerar protein kinases.", "content": "We have shown that nuclei isolated by two methods contain grossly different amounts of cyclic AMP-dependent histone kinase activity. Repeated washing of the isolated nuclei with a low ionic strength buffer removed the majority of the cyclic AMP-dependent histone kinase and cyclic AMP binding activity. Nuclear cyclic AMP-dependent histone kinase activity accounted for only 0.42% of the total cytoplasmic enzyme activity. Similarly, the lactate dehydrogenase activity associated with liver nuclei represented only 0.07% of the total cytoplasmic activity. The isolated liver nuclei contained only 0.27% of the total homogenate glutamate dehydrogenase activity and 1.7%of the total homogenate glucose-6-phosphatase activity. The cyclic AMP-dependent histone kinase behaves as a cytoplasmic rather than a nuclear enzyme. We have also shown that using crude extracts, one can achieve separation of the two nuclear casein kinases, NI and NII, on sucrose density gradients in the presence of 0.5M NaCl. Nuclear casein kinases NI and NII had sedimentation coefficients of 3.0 and 593 S, respectively, in the presence of 0.5 M NaCl. Under conditions of low ionic strength, all of the casein kinase activity in the crude nuclear extract sedimented as one peak with a seminentation coefficient of 7.3 S. The aggregation-disaggregation which occurred in the crude extract was reversible and was mainly due to the aggregative and disaggregative properties of casein kinase NII. The two nuclear casein kinases have different affinities for chromatin. When nuclei were disrupted in a hypotonic solution and extracted with a buffercontaining 0.14 M NaCl, casein kinase NII could be completely extracted from the viscous nuclear material. Although a significant amount of casein kinase NI was extracted by the buffer containing 0.14 M NaCl, re-extraction of the nuclear material with a buffer containing 0.5 M NaCl yielded substantial amounts of casein kinase NI, and a final extraction with a buffer containing 1.0 M NaCl yielded measurable amounts of casein kinase NI. No casein kinase NII activity could be detected in the 0.5 M and 1.0M NaCl extracts.", "contents": "Rat liver nuclerar protein kinases. We have shown that nuclei isolated by two methods contain grossly different amounts of cyclic AMP-dependent histone kinase activity. Repeated washing of the isolated nuclei with a low ionic strength buffer removed the majority of the cyclic AMP-dependent histone kinase and cyclic AMP binding activity. Nuclear cyclic AMP-dependent histone kinase activity accounted for only 0.42% of the total cytoplasmic enzyme activity. Similarly, the lactate dehydrogenase activity associated with liver nuclei represented only 0.07% of the total cytoplasmic activity. The isolated liver nuclei contained only 0.27% of the total homogenate glutamate dehydrogenase activity and 1.7%of the total homogenate glucose-6-phosphatase activity. The cyclic AMP-dependent histone kinase behaves as a cytoplasmic rather than a nuclear enzyme. We have also shown that using crude extracts, one can achieve separation of the two nuclear casein kinases, NI and NII, on sucrose density gradients in the presence of 0.5M NaCl. Nuclear casein kinases NI and NII had sedimentation coefficients of 3.0 and 593 S, respectively, in the presence of 0.5 M NaCl. Under conditions of low ionic strength, all of the casein kinase activity in the crude nuclear extract sedimented as one peak with a seminentation coefficient of 7.3 S. The aggregation-disaggregation which occurred in the crude extract was reversible and was mainly due to the aggregative and disaggregative properties of casein kinase NII. The two nuclear casein kinases have different affinities for chromatin. When nuclei were disrupted in a hypotonic solution and extracted with a buffercontaining 0.14 M NaCl, casein kinase NII could be completely extracted from the viscous nuclear material. Although a significant amount of casein kinase NI was extracted by the buffer containing 0.14 M NaCl, re-extraction of the nuclear material with a buffer containing 0.5 M NaCl yielded substantial amounts of casein kinase NI, and a final extraction with a buffer containing 1.0 M NaCl yielded measurable amounts of casein kinase NI. No casein kinase NII activity could be detected in the 0.5 M and 1.0M NaCl extracts."} {"id": "PMID:164985", "title": "The orientation of cytochrome c oxidase in coupled phospholipid membrane vesicles--a spin-label study.", "content": "Cytochrome oxidase, an enzyme containing six different subunits, has been shown to span the inner mitochrondrial membrane. The arrangement of the subunits within the membrane is unknown. Wh have specifically labeled the 25 000 molecular weight subunit with a spin-label derivative of N-ethylmaleimide, 3-maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (NEM-SL(5)). NEM-SL(5)-lebeled cytochrome oxidase can be incorporated into phospholipid membranes to form coupled vesicles of the Hinkle, Kim & Racker ((1972) Jriol. Chem; 247, 1338-1399) type. The resonance spectrum of NEM-SL(5) is similar in both soluble and vesicular cytochrome oxidase. Since ascorbate has been shown to reduce only spin label that is exposed to the exterior surface of a closed vesicle, we have used ascorbate to determine the NEM-SL(5)-binding site in the coupled vesicles; NEM-SL(5)-labeled cytochrome oxidase vesicles are reduced by 10 mM ascorbate with tau 1/2 of 1 min at 22 degrees C; The rate of reduction is relatively independent of temperature. We conclude that (1) cytochrome oxidase is unidirectionally or preferentially oriented in the vesicle membrane, and (2) the NEM-SL(5)-binding site on the 25 000 molecular weight subunit is exposed to the external aqueous medium.", "contents": "The orientation of cytochrome c oxidase in coupled phospholipid membrane vesicles--a spin-label study. Cytochrome oxidase, an enzyme containing six different subunits, has been shown to span the inner mitochrondrial membrane. The arrangement of the subunits within the membrane is unknown. Wh have specifically labeled the 25 000 molecular weight subunit with a spin-label derivative of N-ethylmaleimide, 3-maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (NEM-SL(5)). NEM-SL(5)-lebeled cytochrome oxidase can be incorporated into phospholipid membranes to form coupled vesicles of the Hinkle, Kim & Racker ((1972) Jriol. Chem; 247, 1338-1399) type. The resonance spectrum of NEM-SL(5) is similar in both soluble and vesicular cytochrome oxidase. Since ascorbate has been shown to reduce only spin label that is exposed to the exterior surface of a closed vesicle, we have used ascorbate to determine the NEM-SL(5)-binding site in the coupled vesicles; NEM-SL(5)-labeled cytochrome oxidase vesicles are reduced by 10 mM ascorbate with tau 1/2 of 1 min at 22 degrees C; The rate of reduction is relatively independent of temperature. We conclude that (1) cytochrome oxidase is unidirectionally or preferentially oriented in the vesicle membrane, and (2) the NEM-SL(5)-binding site on the 25 000 molecular weight subunit is exposed to the external aqueous medium."} {"id": "PMID:164986", "title": "Characteristics of action of prostaglandins on cyclic AMP accumulation in rat anterior pituitary gland.", "content": "Prostaglandins (PGs) were found to lead to a marked stimulation of cyclic AMP accumulation in rat anterior pituitary gland in vitro in the following decreasing order of potency: PG E-1 E-2 GREATER THAN A-1 A-I GREATER THAN F-1ALPHA F-2ALPHA. The effect of PGs is potentiated by theophylline. The stimulatory effect of PGs on cyclic AMP accumulation is already detected 2min after the addition of 1-x 10-7 to 1-x 10-6 M PG E-2 and its maximal effect is reached after approximated 30 min of incubation, with a progressive decrease toward basal cyclic AMP levels at later time intervals. Increased intracellular cyclic AMP concentrations are accompanied by an increased release of the nucleotide into incubation medium. Complete removal of Ca-e+ from the incubation medium by addition of EGTA was found to increase the stimulatory effect of PG E-2 ON CYCLIC AMP accumulation. The action of PGs on hormonal release and cyclic AMP accumulation support the hypothesis of a role of PGs in the mechanism of anterior pituitary hormone (particularly growth hormone) release.", "contents": "Characteristics of action of prostaglandins on cyclic AMP accumulation in rat anterior pituitary gland. Prostaglandins (PGs) were found to lead to a marked stimulation of cyclic AMP accumulation in rat anterior pituitary gland in vitro in the following decreasing order of potency: PG E-1 E-2 GREATER THAN A-1 A-I GREATER THAN F-1ALPHA F-2ALPHA. The effect of PGs is potentiated by theophylline. The stimulatory effect of PGs on cyclic AMP accumulation is already detected 2min after the addition of 1-x 10-7 to 1-x 10-6 M PG E-2 and its maximal effect is reached after approximated 30 min of incubation, with a progressive decrease toward basal cyclic AMP levels at later time intervals. Increased intracellular cyclic AMP concentrations are accompanied by an increased release of the nucleotide into incubation medium. Complete removal of Ca-e+ from the incubation medium by addition of EGTA was found to increase the stimulatory effect of PG E-2 ON CYCLIC AMP accumulation. The action of PGs on hormonal release and cyclic AMP accumulation support the hypothesis of a role of PGs in the mechanism of anterior pituitary hormone (particularly growth hormone) release."} {"id": "PMID:164987", "title": "The conformational states of oxidized and oxygenated beef-heart cytochrome c oxidase.", "content": "1. The \"oxygenated\" form of cytochrome has been generated by treatment of the enzyme with ascorbic acid. 2. \"Oxygenated oxidase\" so generated is stable over long periods (24 h). 3. Sedimentation velocity experiments have shown the \"oxygenated\" oxidase to be a less compact molecule than the oxidized.", "contents": "The conformational states of oxidized and oxygenated beef-heart cytochrome c oxidase. 1. The \"oxygenated\" form of cytochrome has been generated by treatment of the enzyme with ascorbic acid. 2. \"Oxygenated oxidase\" so generated is stable over long periods (24 h). 3. Sedimentation velocity experiments have shown the \"oxygenated\" oxidase to be a less compact molecule than the oxidized."} {"id": "PMID:164988", "title": "The conformational states of cytochrome oxidase in the mitochondrion.", "content": "THE Soret spectrum of \"resting\" cytochrome oxidase in cytochrome-c depleted mitochondria has been determined. The spectrum obtained is dependent on the rate at which the oxidase is turning over. In the least active preparations, the spectrum is almost pure \"oxidized\" oxidase. With increasing activity the spectrum is converted to a mixture of \"oxidized\" and \"oxygenated\" oxidases. It is concluded that the same conformational differences between the two non-reduced forms that are found in the purified enzyme also occur in these cytochrome-c depleted mitochondria.", "contents": "The conformational states of cytochrome oxidase in the mitochondrion. THE Soret spectrum of \"resting\" cytochrome oxidase in cytochrome-c depleted mitochondria has been determined. The spectrum obtained is dependent on the rate at which the oxidase is turning over. In the least active preparations, the spectrum is almost pure \"oxidized\" oxidase. With increasing activity the spectrum is converted to a mixture of \"oxidized\" and \"oxygenated\" oxidases. It is concluded that the same conformational differences between the two non-reduced forms that are found in the purified enzyme also occur in these cytochrome-c depleted mitochondria."} {"id": "PMID:164989", "title": "Effects of Lubrol detergents on adenylate cyclases.", "content": "The nonionic detergent Lubrol WX showed diverse, concentration-dependent effects onbasal and stimulated adenylate cyclases. Above concentrations of 0.001-0.01% Lubrol WX, the basal activity of cyclase from Ehrlich ascites cells was inhibed about 50%, and that from rat fat cells was doubled. In both cases, hormonal sensitivity was lost at 0.01%. These effects were reversed upon dilution of the detergent. It is suggested that solubilization of adenylate cyclases at such low concentrations of Lubrol should be attempted since it is conceivable that loss of hormone sensitivity may then be reversible. Different Lubrol-type detergents may also offer centain advantages, since Lubrol PX effects were not identical with those of Lubrol WX.", "contents": "Effects of Lubrol detergents on adenylate cyclases. The nonionic detergent Lubrol WX showed diverse, concentration-dependent effects onbasal and stimulated adenylate cyclases. Above concentrations of 0.001-0.01% Lubrol WX, the basal activity of cyclase from Ehrlich ascites cells was inhibed about 50%, and that from rat fat cells was doubled. In both cases, hormonal sensitivity was lost at 0.01%. These effects were reversed upon dilution of the detergent. It is suggested that solubilization of adenylate cyclases at such low concentrations of Lubrol should be attempted since it is conceivable that loss of hormone sensitivity may then be reversible. Different Lubrol-type detergents may also offer centain advantages, since Lubrol PX effects were not identical with those of Lubrol WX."} {"id": "PMID:164990", "title": "Effect of Eimeria acervulina infection on nutrient retention with special reference to fat malabsorption in chickens.", "content": "Nutritional balance studies were conducted to determine the effect of Eimeria acervulina infection on the retention of nutrients and the efficiency of utilization of protein and energy in the diet during the course of intestinal coccidiosis in chickens. Both light and electronmicroscopic studies were conducted to elucidate the pathogenesis of fat malabsorption in the infected chickens. The infection with E. acervulina during the acute phase of the disease (day 4 to day 8 postinfection) caused a reduction (P smaller than 0.01) in the retention of percent protein, percent ether extract and percent gross energy of the diet with a concomitant increase (P smaller than 0.01) in the concentration of ether extract and gross energy of the excreta. The metabolizable energy value of the diet was also depressed during this phase. During the recovery phase of the disease (day 9 to day 13 postinfection) infected chickens voided excreta containing a slightly greater concentration of ether extract when compared to the controls but differences in the retention of percent protein and percent gross energy were no longer observed. An increased retention of percent phosphorus also occured during the recovery phase. Studies involving the carcass composition revealed that the efficiency of utilization of protein and metabolizable energy of the diet for tissue deposition was reduced (P smaller than 0.05) during day 0 to day 8 postinfection but only the efficiency of metabolizable energy utilization was found to be depressed (P smaller than 0.05) when data for day 0 to day 14 postinfection were analyzed. Both light and electronmicroscopic studies of the duodenal villi of infected chickens during day 5 to day 6 postinfection revealed accumulation of large globules of fat in the villus epithelial cells parasitized by the gammonts of E. acervulina indicating a possible blackade of \"fat exit\" from these cells.", "contents": "Effect of Eimeria acervulina infection on nutrient retention with special reference to fat malabsorption in chickens. Nutritional balance studies were conducted to determine the effect of Eimeria acervulina infection on the retention of nutrients and the efficiency of utilization of protein and energy in the diet during the course of intestinal coccidiosis in chickens. Both light and electronmicroscopic studies were conducted to elucidate the pathogenesis of fat malabsorption in the infected chickens. The infection with E. acervulina during the acute phase of the disease (day 4 to day 8 postinfection) caused a reduction (P smaller than 0.01) in the retention of percent protein, percent ether extract and percent gross energy of the diet with a concomitant increase (P smaller than 0.01) in the concentration of ether extract and gross energy of the excreta. The metabolizable energy value of the diet was also depressed during this phase. During the recovery phase of the disease (day 9 to day 13 postinfection) infected chickens voided excreta containing a slightly greater concentration of ether extract when compared to the controls but differences in the retention of percent protein and percent gross energy were no longer observed. An increased retention of percent phosphorus also occured during the recovery phase. Studies involving the carcass composition revealed that the efficiency of utilization of protein and metabolizable energy of the diet for tissue deposition was reduced (P smaller than 0.05) during day 0 to day 8 postinfection but only the efficiency of metabolizable energy utilization was found to be depressed (P smaller than 0.05) when data for day 0 to day 14 postinfection were analyzed. Both light and electronmicroscopic studies of the duodenal villi of infected chickens during day 5 to day 6 postinfection revealed accumulation of large globules of fat in the villus epithelial cells parasitized by the gammonts of E. acervulina indicating a possible blackade of \"fat exit\" from these cells."} {"id": "PMID:164991", "title": "A comparison of gel diffusion, fluorescent antibody and virus isolation methods in experimental and natural cases of infectious bursal disease.", "content": "In studies with chicks inoculated with the Sk-1 strain of infectious bursal agent the bursa of Fabricius was found to be the tissue of choice for virus isolation as well as for use in the fluorescent antibody test and the agar gel diffusion test. In separate experiments positive results were obtained until postinoculation days 3 or 4 by the agar gel diffusion test, 5 or 6 by the fluorescent antibody test and 14 by the virus isolation method, respectively. Bursas from chickens involved in seven natural outbreaks of infectious bursal disease were then examined by these three methods. Virus was isolated from six outbreaks and infectious bursal agent antigen was demonstrated in three by the agar gel diffusion test method and seven (three by direct examination and four after one passage in chicks) by the fluorescent antibody test method. Passage in chicks was required when nonspecific fluorescence complicated the interpretation of fluorescent antibody test results.", "contents": "A comparison of gel diffusion, fluorescent antibody and virus isolation methods in experimental and natural cases of infectious bursal disease. In studies with chicks inoculated with the Sk-1 strain of infectious bursal agent the bursa of Fabricius was found to be the tissue of choice for virus isolation as well as for use in the fluorescent antibody test and the agar gel diffusion test. In separate experiments positive results were obtained until postinoculation days 3 or 4 by the agar gel diffusion test, 5 or 6 by the fluorescent antibody test and 14 by the virus isolation method, respectively. Bursas from chickens involved in seven natural outbreaks of infectious bursal disease were then examined by these three methods. Virus was isolated from six outbreaks and infectious bursal agent antigen was demonstrated in three by the agar gel diffusion test method and seven (three by direct examination and four after one passage in chicks) by the fluorescent antibody test method. Passage in chicks was required when nonspecific fluorescence complicated the interpretation of fluorescent antibody test results."} {"id": "PMID:164992", "title": "Investigation of factors of probable significance in the pathogenesis of pneumonic pasteurellosis in cattle.", "content": "Six groups of ten beef calves six to eight months of age were shipped from western Canada and observed untreated for one week after arrival. The following parameters were measured daily: body temperature, plasma fibrinogen, nasal bacterial mean colony counts of Pasteurella hemolytica and Pasteurella multocida, total and differential leukoyte counts, packed cell volumes and the following, twice during the week: serum and nasal antibody titres to P. hemolytica and parainfluenza-3 virus. The lungs from 44 of the calves were obtained at post mortem and given a numerical score based on the degree of pneumonia present. Animals were designated SICK and WELL according to body temperature and plasma fibrinogen. The SICK animals had higher nasal mean colony counts of P. hemolytica than the WELL animals. The SICK animals had lower levels of serum antibody to P. hemolytica than the WELL on day 1 but had a greater rise in titre over the week than did the WELL animals. Both groups were similar with regard to serum antibody to parainfluenza-3 virus and there was little change in these titres. The SICK animals had a much greater degree of pneumonia than the WELL. The values of some of the parameters were combined with the data of previously studied animals in order to provide a comparison of SICK and WELL with larger numbers of animals.", "contents": "Investigation of factors of probable significance in the pathogenesis of pneumonic pasteurellosis in cattle. Six groups of ten beef calves six to eight months of age were shipped from western Canada and observed untreated for one week after arrival. The following parameters were measured daily: body temperature, plasma fibrinogen, nasal bacterial mean colony counts of Pasteurella hemolytica and Pasteurella multocida, total and differential leukoyte counts, packed cell volumes and the following, twice during the week: serum and nasal antibody titres to P. hemolytica and parainfluenza-3 virus. The lungs from 44 of the calves were obtained at post mortem and given a numerical score based on the degree of pneumonia present. Animals were designated SICK and WELL according to body temperature and plasma fibrinogen. The SICK animals had higher nasal mean colony counts of P. hemolytica than the WELL animals. The SICK animals had lower levels of serum antibody to P. hemolytica than the WELL on day 1 but had a greater rise in titre over the week than did the WELL animals. Both groups were similar with regard to serum antibody to parainfluenza-3 virus and there was little change in these titres. The SICK animals had a much greater degree of pneumonia than the WELL. The values of some of the parameters were combined with the data of previously studied animals in order to provide a comparison of SICK and WELL with larger numbers of animals."} {"id": "PMID:164993", "title": "Correlation between the serum neutralization test and the indirect immunofluorescent test for the detection of specific antibodies to infectious bovine rhinotracheitis virus.", "content": "Comparative titrations show that immunofluorescence on infected rabbit kidney cells is relatively as sensitive as the neutralization test for the detection of antibodies to the infectious bovine rhinotracheitis virus. When calf testis cells infected with this virus are used for the detection of antibodies by the indirect immunofluorescent test nonspecific staining is high. This nonspecific reaction is absent when rabbit kidney cells are used.", "contents": "Correlation between the serum neutralization test and the indirect immunofluorescent test for the detection of specific antibodies to infectious bovine rhinotracheitis virus. Comparative titrations show that immunofluorescence on infected rabbit kidney cells is relatively as sensitive as the neutralization test for the detection of antibodies to the infectious bovine rhinotracheitis virus. When calf testis cells infected with this virus are used for the detection of antibodies by the indirect immunofluorescent test nonspecific staining is high. This nonspecific reaction is absent when rabbit kidney cells are used."} {"id": "PMID:164994", "title": "Improvements in the modified direct complement fixation test and its application in the detection of bluetongue antibodies in cattle and sheep sera.", "content": "In this study, improvements were made in the technique and the preparation of the antigen. It was possible to perform three extractions and elutions resulting in a soluble reactive preparation from each batch of infected mouse brain. This led to an appreciable increase in the yield of highly reactive antigen. The presence of bluetongue antibodies was not detected in 13,210 sheep sera. Of the 13,486 bovine sera tested, only three questionable reactions were obtained. It was possible to determine that two of these animals were imported. Various isolation methods, including transmission trials to susceptible sheep followed by serological tests on the sheep sera, failed to confirm the infection in the three reactors.", "contents": "Improvements in the modified direct complement fixation test and its application in the detection of bluetongue antibodies in cattle and sheep sera. In this study, improvements were made in the technique and the preparation of the antigen. It was possible to perform three extractions and elutions resulting in a soluble reactive preparation from each batch of infected mouse brain. This led to an appreciable increase in the yield of highly reactive antigen. The presence of bluetongue antibodies was not detected in 13,210 sheep sera. Of the 13,486 bovine sera tested, only three questionable reactions were obtained. It was possible to determine that two of these animals were imported. Various isolation methods, including transmission trials to susceptible sheep followed by serological tests on the sheep sera, failed to confirm the infection in the three reactors."} {"id": "PMID:164995", "title": "Type 1 and type 2 herpes simplex uvietis in immune rabbits: importance of pure virus preparation.", "content": "Systemic immunization with type 1 herpes simplex virus (HSV) protected rabbits from developing uveitis when they were challenged intravitreally with either purified type 1 or purufied type 2 HSV. But when an HSV preparation contaminated with a nonviral foreign antigen (fetal calf serum) was used for both systemic immunization and challenge, the immunization against HSV failed to exert a protective effect because the fetal calf serum had produced a nonviral immunologic reaction in the uveal tract. This clearly indicates the importance of preparing virus properly for use in experiments of this nature.", "contents": "Type 1 and type 2 herpes simplex uvietis in immune rabbits: importance of pure virus preparation. Systemic immunization with type 1 herpes simplex virus (HSV) protected rabbits from developing uveitis when they were challenged intravitreally with either purified type 1 or purufied type 2 HSV. But when an HSV preparation contaminated with a nonviral foreign antigen (fetal calf serum) was used for both systemic immunization and challenge, the immunization against HSV failed to exert a protective effect because the fetal calf serum had produced a nonviral immunologic reaction in the uveal tract. This clearly indicates the importance of preparing virus properly for use in experiments of this nature."} {"id": "PMID:164996", "title": "Clostridium welchii corneal ulcer--a case report.", "content": "A case of corneal ulcer in a 10-year-old Nigerian boy in which clostridium welchii and achromobacter were isolated is reported. The absence of trauma and rarity of only corneal involvement in a clostridial infection is emphasized. The bacteriology of the clostridial infection is emphasized. The bacteriology of the clostridial ocular infections is reviewed, the media necessary for isolation of the organism and the symbiotic relationship with other bacteria are discussed. The clinical course of the disease with uneventful recovery of the patient is emphasized.", "contents": "Clostridium welchii corneal ulcer--a case report. A case of corneal ulcer in a 10-year-old Nigerian boy in which clostridium welchii and achromobacter were isolated is reported. The absence of trauma and rarity of only corneal involvement in a clostridial infection is emphasized. The bacteriology of the clostridial infection is emphasized. The bacteriology of the clostridial ocular infections is reviewed, the media necessary for isolation of the organism and the symbiotic relationship with other bacteria are discussed. The clinical course of the disease with uneventful recovery of the patient is emphasized."} {"id": "PMID:164997", "title": "Hydrogen cyanide, a secondary metabolite of Pseudomonas aeruginosa.", "content": "Seventy-four of 110 strains of Pseudomonas aeruginosa tested produced detectable amounts of HCN from growth in 2% peptone or nutrient agar. Of the 25 species of12 bacterial and fungal genera tested, other than P. aeruginosa, only P. fluorescens and P. polycolor gave positive HCN tests. Cyanide is produced after cessation of active growth. Iron was stimulatory to cyanogenesis in concentration above 1 muM, while copper, zinc, cobalt, and manganese at concentrations of 20 muM had no effect. Cyanogenesis id dependent on the temperature of incubation within ranges which allow complete growth. Inorganic phosphate in concentrations between 90 and 300 mM allows growth but inhibits HCN production. Growth of cells anaerobically, using nitrate as the electron acceptor, results in low cyanide yields, which can be partially reversed by subsequent aerobic incubation. These results indicate that HCN is a secondary metabolite of P. aeruginosa.", "contents": "Hydrogen cyanide, a secondary metabolite of Pseudomonas aeruginosa. Seventy-four of 110 strains of Pseudomonas aeruginosa tested produced detectable amounts of HCN from growth in 2% peptone or nutrient agar. Of the 25 species of12 bacterial and fungal genera tested, other than P. aeruginosa, only P. fluorescens and P. polycolor gave positive HCN tests. Cyanide is produced after cessation of active growth. Iron was stimulatory to cyanogenesis in concentration above 1 muM, while copper, zinc, cobalt, and manganese at concentrations of 20 muM had no effect. Cyanogenesis id dependent on the temperature of incubation within ranges which allow complete growth. Inorganic phosphate in concentrations between 90 and 300 mM allows growth but inhibits HCN production. Growth of cells anaerobically, using nitrate as the electron acceptor, results in low cyanide yields, which can be partially reversed by subsequent aerobic incubation. These results indicate that HCN is a secondary metabolite of P. aeruginosa."} {"id": "PMID:164998", "title": "Relationship between the DNA content and mesosome number in cells of Bacillus.", "content": "In cells of Bacillus there is evidence that deoxyribonucleic acid forms an association with some membranous structure within the cell, possibly mesosomes. Cells of varieties of Bacillus cereus and Bacillus subtilis were examined to see if any quantitative relationship existed between the numbers of mesosomes and DNA content. No direct relationship could be domonstrated. However, cells of Bacillus cereus var. alesti A(-) maintained a characteristic and constant DNA content and number of mesosomes regardless of growth conditions. During sporulation, a variant of A(-), termed A(-)3, SEQUESTERS ITS DNA at both ends of the cell, leaving a small amount of DNA but no mesosomes in the center compartment. Since this center compartment is capableof growth and division upon replacement in fresh medium (rejuventation) it was examinedfor mesosome content as DNA synthesis and division were initiated. In most cells, acentral mesosome was formed at the site of cell septum formation; however, the presenceof a mesosome was not an absolute prerequisite for cell division. We propose that atthe onset of cell growth, mesosomes primarily function in the process of cell septum formation. As growth and division proceed, mesosomes are produced in characteristicnumbers and may act as the site of DNA synthesis and (or) segregation.", "contents": "Relationship between the DNA content and mesosome number in cells of Bacillus. In cells of Bacillus there is evidence that deoxyribonucleic acid forms an association with some membranous structure within the cell, possibly mesosomes. Cells of varieties of Bacillus cereus and Bacillus subtilis were examined to see if any quantitative relationship existed between the numbers of mesosomes and DNA content. No direct relationship could be domonstrated. However, cells of Bacillus cereus var. alesti A(-) maintained a characteristic and constant DNA content and number of mesosomes regardless of growth conditions. During sporulation, a variant of A(-), termed A(-)3, SEQUESTERS ITS DNA at both ends of the cell, leaving a small amount of DNA but no mesosomes in the center compartment. Since this center compartment is capableof growth and division upon replacement in fresh medium (rejuventation) it was examinedfor mesosome content as DNA synthesis and division were initiated. In most cells, acentral mesosome was formed at the site of cell septum formation; however, the presenceof a mesosome was not an absolute prerequisite for cell division. We propose that atthe onset of cell growth, mesosomes primarily function in the process of cell septum formation. As growth and division proceed, mesosomes are produced in characteristicnumbers and may act as the site of DNA synthesis and (or) segregation."} {"id": "PMID:164999", "title": "Host response to infection by Coxiella burneti.", "content": "A host response to infection by Coxiella burneti was investigated. Infectedyolk sacs were harvested from embryonated eggs and assayed for glycolytic activity. Assays of glycolytic enzymes included glucose isomerase, aldolase, phosphofructokinase,fructose-1,6-diphoshatase, glyceraldehyde-3-phosphate dehydrogenase, enolase, and pyruvate kinase. No significant differences in enzymatic activity between normal and infected tissues through the 12th day was observed. From the 13th day through the 16thday, the glycolytic activity of normal tissues decreased. Glycolytic activity of infected tissues did not decrease, but showed a gradual increase during this same time period. Embryos from infected eggs demonstrated a gradual decrease in total weight fromthe 12th day until death occurred on the 16th day.", "contents": "Host response to infection by Coxiella burneti. A host response to infection by Coxiella burneti was investigated. Infectedyolk sacs were harvested from embryonated eggs and assayed for glycolytic activity. Assays of glycolytic enzymes included glucose isomerase, aldolase, phosphofructokinase,fructose-1,6-diphoshatase, glyceraldehyde-3-phosphate dehydrogenase, enolase, and pyruvate kinase. No significant differences in enzymatic activity between normal and infected tissues through the 12th day was observed. From the 13th day through the 16thday, the glycolytic activity of normal tissues decreased. Glycolytic activity of infected tissues did not decrease, but showed a gradual increase during this same time period. Embryos from infected eggs demonstrated a gradual decrease in total weight fromthe 12th day until death occurred on the 16th day."} {"id": "PMID:165000", "title": "[Rubella virus. III. Purification of infected or non-infected Vero cell membranes].", "content": "Separation of Vero cell membrane in a discontinuous sucrose gradient reveals five fractions. After infection a sixth fraction appears. It contains virioins but mostly modified membranes with subunits 5-6 nm in diameter, probably the hemagglutinin. None of the enzymes used was associated with this fraction. No modification of the other fractions was observed after infection.", "contents": "[Rubella virus. III. Purification of infected or non-infected Vero cell membranes]. Separation of Vero cell membrane in a discontinuous sucrose gradient reveals five fractions. After infection a sixth fraction appears. It contains virioins but mostly modified membranes with subunits 5-6 nm in diameter, probably the hemagglutinin. None of the enzymes used was associated with this fraction. No modification of the other fractions was observed after infection."} {"id": "PMID:165001", "title": "Solitary liver nodules.", "content": "There has been confusion in the literature over the nomenclature of solitary liver nodules. Several such lesions have recently been reported in patients taking oral contraceptives. Similarities exist between these cases that suggest they may be examples of focal nodular hyperplasia. Here three further cases are presented. The criteria for making the diagnosis and its importance are discussed.", "contents": "Solitary liver nodules. There has been confusion in the literature over the nomenclature of solitary liver nodules. Several such lesions have recently been reported in patients taking oral contraceptives. Similarities exist between these cases that suggest they may be examples of focal nodular hyperplasia. Here three further cases are presented. The criteria for making the diagnosis and its importance are discussed."} {"id": "PMID:165002", "title": "Medical Research Council of Canada therapeutic trial of human growth hormone: first 5 years of therapy.", "content": "The Medical Research Council of Canada has initiated human growth hormone (hGH) therapy in 151 patients with documented complete hGH deficiency that was idiopathic in 76% of cases, secondary to craniopharyngioma (organic) in 17% and of varied cause in 7%. Approximately 50% of the patients with idiopathic disease had isolated hGH deficiency; during therapy thyroid deficiency developed in five patients and cortisol deficiency in three. A similar increase in mean height velocity occurred in the first treatment phase for patients less than 12 years old (0.93 plus or minus 0.30 cm/mo) and those 12 years and older (0.86 plus or minus 0.29 cm/mo). Although subsequent courses of hGH therapy yielded significantly diminished response in both age groups, this diminution was not progressive: the height velocity of the younger patients returned to 0.82 plus or minus 0.26 cm/ml in the fifth therapy phase. The mean height velocity attained at the optimal dosage (0.20 to 0.29 units/kg three times per week) for each age group did not differ significantly. Despite therapy being carried out for only 6 months of the year, normal increment ratios for height age and bone age against chronologic age were observed in the patients with idiopathic disease. In only four patients did treatment failure occur, and three of these were more than 20 years old. The addition of fluoxymesterone (10 mg/d) to the hGH therapeutic regimen (15 units/wk), when diminished response to hGH alone became evident, promoted an enhanced growth response in 9 of 11 older patients. These data indicate that age of the patient and dosage of hGH, but not diagnostic category, were important influences on the response to therapy. Younger patients responded best and maintained a higher mean growth velocity than older patients during intermittent hGH therapy", "contents": "Medical Research Council of Canada therapeutic trial of human growth hormone: first 5 years of therapy. The Medical Research Council of Canada has initiated human growth hormone (hGH) therapy in 151 patients with documented complete hGH deficiency that was idiopathic in 76% of cases, secondary to craniopharyngioma (organic) in 17% and of varied cause in 7%. Approximately 50% of the patients with idiopathic disease had isolated hGH deficiency; during therapy thyroid deficiency developed in five patients and cortisol deficiency in three. A similar increase in mean height velocity occurred in the first treatment phase for patients less than 12 years old (0.93 plus or minus 0.30 cm/mo) and those 12 years and older (0.86 plus or minus 0.29 cm/mo). Although subsequent courses of hGH therapy yielded significantly diminished response in both age groups, this diminution was not progressive: the height velocity of the younger patients returned to 0.82 plus or minus 0.26 cm/ml in the fifth therapy phase. The mean height velocity attained at the optimal dosage (0.20 to 0.29 units/kg three times per week) for each age group did not differ significantly. Despite therapy being carried out for only 6 months of the year, normal increment ratios for height age and bone age against chronologic age were observed in the patients with idiopathic disease. In only four patients did treatment failure occur, and three of these were more than 20 years old. The addition of fluoxymesterone (10 mg/d) to the hGH therapeutic regimen (15 units/wk), when diminished response to hGH alone became evident, promoted an enhanced growth response in 9 of 11 older patients. These data indicate that age of the patient and dosage of hGH, but not diagnostic category, were important influences on the response to therapy. Younger patients responded best and maintained a higher mean growth velocity than older patients during intermittent hGH therapy"} {"id": "PMID:165003", "title": "The structure of a sulfated glycoprotein of chick allantoic fluid: methylation and periodate oxidation.", "content": "The structure of an antigenic, sulfated glycoprotein from chick chorioallantoic fluid has been investigated by exogalactosidase digestion, methylation and mass spectral analyses, periodate oxidation, and Smith degradation. The main carbohydrate chains are composed of D-galactosyl residues linked at C-3 and 2-acetamido-2-deoxyglucose residues linked at C-4. Fucose and N-acetylneuraminic acid residues are nonreducing terminal groups, and the N-acetylneuraminic acid groups are linked to the D-galactose residues at C-3. Most of the sulfate groups (91% of the sulfate) are located on C-6 of the 2-acetamido-2-deoxyglucose residues, and the rest on C-6 of the D-galactose residues. A large number of the D-galactose residues (36.9% of the total) are present as nonreducing terminal groups and another 21.7% of the D-galactose residues are in penultimate position to the nonreducing terminal N-acetylneuraminic acid residues. Although mild periodate oxidation indicates the presence of D-galactose in furanoside form (5.5% of total D-galactose), no 5-O-methyl derivative of D-galactose was observed on methylation.", "contents": "The structure of a sulfated glycoprotein of chick allantoic fluid: methylation and periodate oxidation. The structure of an antigenic, sulfated glycoprotein from chick chorioallantoic fluid has been investigated by exogalactosidase digestion, methylation and mass spectral analyses, periodate oxidation, and Smith degradation. The main carbohydrate chains are composed of D-galactosyl residues linked at C-3 and 2-acetamido-2-deoxyglucose residues linked at C-4. Fucose and N-acetylneuraminic acid residues are nonreducing terminal groups, and the N-acetylneuraminic acid groups are linked to the D-galactose residues at C-3. Most of the sulfate groups (91% of the sulfate) are located on C-6 of the 2-acetamido-2-deoxyglucose residues, and the rest on C-6 of the D-galactose residues. A large number of the D-galactose residues (36.9% of the total) are present as nonreducing terminal groups and another 21.7% of the D-galactose residues are in penultimate position to the nonreducing terminal N-acetylneuraminic acid residues. Although mild periodate oxidation indicates the presence of D-galactose in furanoside form (5.5% of total D-galactose), no 5-O-methyl derivative of D-galactose was observed on methylation."} {"id": "PMID:165008", "title": "Methylation of rat liver mitochondrial deoxyribonucleic acid by chemical carcinogens and associated alterations in physical properties.", "content": "The formation of 7-methylguanine in rat liver mitochondrial DNA following the administration of the powerful carcinogen, dimethylnitrosamine, and the weak carcinogen, methyl methanesulphonate was measured and compared to the alkylation of nuclear DNA by these agents. At all doses tested mitochondrial DNA was alkylated more extensively than nuclear DNA by dimethylnitrosamine but both types of cellular DNA were alkylated to about the same extent by methyl methanesulphonate. The physical structure of rat liver mitochondrial DNA isolated from animals treated with these agents was investigated by electrophoresis in agarose gels and by isopycnic centrifugation in CsCl gradients. These procedures carried out in the presence of ethidium bromide, an intercalating dye, separate closed circular forms of mitochondrial DNA from open circular molecules (containing a single-strand break) and linear molecules. Administration of dimethylnitrosamine produced a considerable decrease in the amount of mitochondrial DNA which could be isolated in the closed circular form and at higher doses of dimethylnitrosamine no closed circular mitochondrial DNA could be found. Methyl methanesulphonate was less effective at reducing the amount of closed circular mitochondrial DNA. One explantation of these results is that dimethylnitrosamine leads to strand breaks in mitochondrial DNA and the possible use of this system to investigate carcinogen-induced breaks in DNA is discussed.", "contents": "Methylation of rat liver mitochondrial deoxyribonucleic acid by chemical carcinogens and associated alterations in physical properties. The formation of 7-methylguanine in rat liver mitochondrial DNA following the administration of the powerful carcinogen, dimethylnitrosamine, and the weak carcinogen, methyl methanesulphonate was measured and compared to the alkylation of nuclear DNA by these agents. At all doses tested mitochondrial DNA was alkylated more extensively than nuclear DNA by dimethylnitrosamine but both types of cellular DNA were alkylated to about the same extent by methyl methanesulphonate. The physical structure of rat liver mitochondrial DNA isolated from animals treated with these agents was investigated by electrophoresis in agarose gels and by isopycnic centrifugation in CsCl gradients. These procedures carried out in the presence of ethidium bromide, an intercalating dye, separate closed circular forms of mitochondrial DNA from open circular molecules (containing a single-strand break) and linear molecules. Administration of dimethylnitrosamine produced a considerable decrease in the amount of mitochondrial DNA which could be isolated in the closed circular form and at higher doses of dimethylnitrosamine no closed circular mitochondrial DNA could be found. Methyl methanesulphonate was less effective at reducing the amount of closed circular mitochondrial DNA. One explantation of these results is that dimethylnitrosamine leads to strand breaks in mitochondrial DNA and the possible use of this system to investigate carcinogen-induced breaks in DNA is discussed."} {"id": "PMID:165009", "title": "Synthesis of threo-4,5-dihydroxy diastereomers of sphinganine;.", "content": "The threo-4,5-dihydroxy diastereomers of sphinganine were prepared by the following sequence of reactions: (a) benzoylation of sphingenine to the tribenzoyl derivative; (b) osmylation followed by resolution of the mixture of threo-4,5-dihydroxy tribenzoyl (DHTBS) diastereomers; and (c) alkaline hydrolysis to yield the threo-4,5-dihydroxysphinganines (DHS). Carbon atoms 4 and 5 of the high and low melting threo-4,5-DHTBS diastereomers and the compounds derived from them were tentatively assigned 4R, 5S and 5R configurations, respectively;", "contents": "Synthesis of threo-4,5-dihydroxy diastereomers of sphinganine;. The threo-4,5-dihydroxy diastereomers of sphinganine were prepared by the following sequence of reactions: (a) benzoylation of sphingenine to the tribenzoyl derivative; (b) osmylation followed by resolution of the mixture of threo-4,5-dihydroxy tribenzoyl (DHTBS) diastereomers; and (c) alkaline hydrolysis to yield the threo-4,5-dihydroxysphinganines (DHS). Carbon atoms 4 and 5 of the high and low melting threo-4,5-DHTBS diastereomers and the compounds derived from them were tentatively assigned 4R, 5S and 5R configurations, respectively;"} {"id": "PMID:165010", "title": "Arrangement of lipid and protein in human serum high density lipoproteins: a proposed model.", "content": "Based on size and compositional data, models for the two major density subclasses of human serum high density lipoproteins have been developed. Descriptions of both the surface structure of the high density lipoproteins and the structure of their apolar core regions are integral parts of these models. The surface is described as a mosaic of amphiphilic lipid and helical protein regions. The conformation and orientation of the various apolar lipid components as restricted by the surface organization is discussed.", "contents": "Arrangement of lipid and protein in human serum high density lipoproteins: a proposed model. Based on size and compositional data, models for the two major density subclasses of human serum high density lipoproteins have been developed. Descriptions of both the surface structure of the high density lipoproteins and the structure of their apolar core regions are integral parts of these models. The surface is described as a mosaic of amphiphilic lipid and helical protein regions. The conformation and orientation of the various apolar lipid components as restricted by the surface organization is discussed."} {"id": "PMID:165011", "title": "An ESR Study of the mobility of the cholestane spin label in oriented lecithin-cholesterol multibilayers.", "content": "The motion of the cholestane spin label in oriented lecithin-cholesterol multibilayers is described in terms of a rotational diffusion about the long molecular axis with diffusion coefficient D parrell and a restricted random librational motion about axes perpendicular to the long axis with diffusion coefficient D1. The diffusion coefficients have been determined from the angular dependence of the ESR line shape at various temperatures and cholesterol contents. The temperature dependence of D parrell and D1 clearly shows the transition from the gel to liquid crystalline phase. Increasing amounts of cholesterol reduce the transition temperature. A strong reduction is found from o to 10 mole % cholesterol. At 50 mole % no longer a sharp transition is observed. In the temperature range from 40 to 80 degrees C the range of D is about 10 times larger than the range of D parrell, indicating a high activation energy for the librational motion arising from a strong hindrance by interaction with surrounding molecules. Cholesterol contents up to 10-20 mole % give an increase of D parrell and D1, arising from strong decrease of the transition temperature in this range. Above 10-20 mole % a reduction of D parrell and D1 is found. However, the effect of cholesterol is much stronger on D1 than on D parrell. In the liquid crystalline phase at about 60 degrees C the effect of cholesterol on D parrell is even negligible, while D1 strongly changes. This indicates that in the liquid crystalline phase only the librational motion is influenced by cholesterol, due to a denser packing of the molecules in the bilayer.", "contents": "An ESR Study of the mobility of the cholestane spin label in oriented lecithin-cholesterol multibilayers. The motion of the cholestane spin label in oriented lecithin-cholesterol multibilayers is described in terms of a rotational diffusion about the long molecular axis with diffusion coefficient D parrell and a restricted random librational motion about axes perpendicular to the long axis with diffusion coefficient D1. The diffusion coefficients have been determined from the angular dependence of the ESR line shape at various temperatures and cholesterol contents. The temperature dependence of D parrell and D1 clearly shows the transition from the gel to liquid crystalline phase. Increasing amounts of cholesterol reduce the transition temperature. A strong reduction is found from o to 10 mole % cholesterol. At 50 mole % no longer a sharp transition is observed. In the temperature range from 40 to 80 degrees C the range of D is about 10 times larger than the range of D parrell, indicating a high activation energy for the librational motion arising from a strong hindrance by interaction with surrounding molecules. Cholesterol contents up to 10-20 mole % give an increase of D parrell and D1, arising from strong decrease of the transition temperature in this range. Above 10-20 mole % a reduction of D parrell and D1 is found. However, the effect of cholesterol is much stronger on D1 than on D parrell. In the liquid crystalline phase at about 60 degrees C the effect of cholesterol on D parrell is even negligible, while D1 strongly changes. This indicates that in the liquid crystalline phase only the librational motion is influenced by cholesterol, due to a denser packing of the molecules in the bilayer."} {"id": "PMID:165012", "title": "An ESR Spin label study of structural and dynamical properties of oriented lecithin-cholesterol multibilayers.", "content": "Oriented dipalmitoyllecithin-cholesterol multibilayers with 11% water have been studied with the cholestane spin label. From the ESR spectra the order parameters and the mobility of the spin label about its long axis have been calculated. The results on pure lecithin multibilayers indicate a transition from gel to liquid crystalline phase at 52 plus or minus 2 degrees C. In the gel phase the lecithin alkyl chains are highly ordered, but tilted with respect to the normal to the bilayers by about 25 degrees. Above 52 degrees C the tilt disappears and the mobility of the cholestane spin label increases, indicating an increase of mobility of the lecithin alkyl chains. When cholesterol is added, below about 52 degrees C a decrease of order is found. Furthermore, already small cholesterol contents (smaller than or equal to 10 mole %) remove the tilt. Above about 52 degrees C cholesterol improves the order by decreasing the amplitude of the librational motions. Cholesterol lowers the transition temperature of the system and reduces the mobility of the lecithin alkyl chains in the liquid crystalline phase. However an increase in mobility is found at cholesterol contents up to 10 mole %. A very broad phase transition is observed at 50 mole % cholesterol. In all systems an increase in temperature results in a reduction of order through an increase of the amplitude of the librational motions of the molecules. The librational motions are to some extent cooperative. The asymmetry of the order matrix is found to be a measure for the lateral ordering. Cholesterol increases the lateral ordering, indicating that the flat cholesterol molecules orient parallel to each other.", "contents": "An ESR Spin label study of structural and dynamical properties of oriented lecithin-cholesterol multibilayers. Oriented dipalmitoyllecithin-cholesterol multibilayers with 11% water have been studied with the cholestane spin label. From the ESR spectra the order parameters and the mobility of the spin label about its long axis have been calculated. The results on pure lecithin multibilayers indicate a transition from gel to liquid crystalline phase at 52 plus or minus 2 degrees C. In the gel phase the lecithin alkyl chains are highly ordered, but tilted with respect to the normal to the bilayers by about 25 degrees. Above 52 degrees C the tilt disappears and the mobility of the cholestane spin label increases, indicating an increase of mobility of the lecithin alkyl chains. When cholesterol is added, below about 52 degrees C a decrease of order is found. Furthermore, already small cholesterol contents (smaller than or equal to 10 mole %) remove the tilt. Above about 52 degrees C cholesterol improves the order by decreasing the amplitude of the librational motions. Cholesterol lowers the transition temperature of the system and reduces the mobility of the lecithin alkyl chains in the liquid crystalline phase. However an increase in mobility is found at cholesterol contents up to 10 mole %. A very broad phase transition is observed at 50 mole % cholesterol. In all systems an increase in temperature results in a reduction of order through an increase of the amplitude of the librational motions of the molecules. The librational motions are to some extent cooperative. The asymmetry of the order matrix is found to be a measure for the lateral ordering. Cholesterol increases the lateral ordering, indicating that the flat cholesterol molecules orient parallel to each other."} {"id": "PMID:165013", "title": "Intervesicular phospholipid exchange. An NMR study.", "content": "Phospholipid exchange between phosphatidylinositol and phosphatidylcholine ?vesicles has been studied by NMR spectroscopy with use of hydrophilic paramagnetic lanthanide probes (Pr-3+ and Eu-3+ ions). The dependence of the lanthanide induced shifts in the1-H and 31-P NMR spectra on the phospholipid composition of the vesicles could be used for its quantitative evaluation. The method has been proved to be applicable for studying phospholipid exchange stimulated by soluble proteins (postmicrosomal supernatant fraction) from rat liver. Furthermore it has been shown that the phospholipid molecules newly introduced by protein-stimulated exchange are predominantly incorporated into the outermonolayer of the vesicular bilayer membrane. This makes it possible to produce liposomes with asymmetric distribution of the phospholipids across the bilayer.", "contents": "Intervesicular phospholipid exchange. An NMR study. Phospholipid exchange between phosphatidylinositol and phosphatidylcholine ?vesicles has been studied by NMR spectroscopy with use of hydrophilic paramagnetic lanthanide probes (Pr-3+ and Eu-3+ ions). The dependence of the lanthanide induced shifts in the1-H and 31-P NMR spectra on the phospholipid composition of the vesicles could be used for its quantitative evaluation. The method has been proved to be applicable for studying phospholipid exchange stimulated by soluble proteins (postmicrosomal supernatant fraction) from rat liver. Furthermore it has been shown that the phospholipid molecules newly introduced by protein-stimulated exchange are predominantly incorporated into the outermonolayer of the vesicular bilayer membrane. This makes it possible to produce liposomes with asymmetric distribution of the phospholipids across the bilayer."} {"id": "PMID:165014", "title": "13-C NMR investigation of phospholipid membranes with the aid of shift reagents.", "content": "13-C NMR spectra of sonicated phospholipid dispersions have been investigated with the aid of paramagnetic ions (Pr-3+) as shift reagents. This method permits discrimination between the outer and the inner surfaces of the vesicular membrane and gives a larger variety of signals than 1-H NMR. The lanthanide induced shifts have been found to depend on other ions present and on the lipid composition of the membrane.", "contents": "13-C NMR investigation of phospholipid membranes with the aid of shift reagents. 13-C NMR spectra of sonicated phospholipid dispersions have been investigated with the aid of paramagnetic ions (Pr-3+) as shift reagents. This method permits discrimination between the outer and the inner surfaces of the vesicular membrane and gives a larger variety of signals than 1-H NMR. The lanthanide induced shifts have been found to depend on other ions present and on the lipid composition of the membrane."} {"id": "PMID:165015", "title": "Phospholipid unsaturation and plasma membrane organization.", "content": "A comparison has been made between the unsaturation of plasma-membrane phospholipids,present in the human erythrocyte, rat liver, mouse liver and a rapidly growing rat hepatoma. Of the double bonds present in the hydrocarbon chains of the membrane phospholipids,onethird is contributed by sphingomyelin plus phosphatidyl choline and the remainder by phosphatidyl serine, ethanolamine and inositol. Assuming that the phospholipids are asymmetrically distributed in the two leaflets of the bilayer in general, the consequences of this asymmetry in combination with cholesterol content and fatty acid distribution on plasma membrane organization and function are discussed. It is suggested, that the organizational disposition of plasma membrane components other than phospholipids is at least related if not dependent upon the latter's asymmetric distribution in the bilayer.", "contents": "Phospholipid unsaturation and plasma membrane organization. A comparison has been made between the unsaturation of plasma-membrane phospholipids,present in the human erythrocyte, rat liver, mouse liver and a rapidly growing rat hepatoma. Of the double bonds present in the hydrocarbon chains of the membrane phospholipids,onethird is contributed by sphingomyelin plus phosphatidyl choline and the remainder by phosphatidyl serine, ethanolamine and inositol. Assuming that the phospholipids are asymmetrically distributed in the two leaflets of the bilayer in general, the consequences of this asymmetry in combination with cholesterol content and fatty acid distribution on plasma membrane organization and function are discussed. It is suggested, that the organizational disposition of plasma membrane components other than phospholipids is at least related if not dependent upon the latter's asymmetric distribution in the bilayer."} {"id": "PMID:165016", "title": "Relationship between serum cholinesterase and low density lipoproteins in children with nephrotic syndrome.", "content": "1. A significant increase in the activity of serum cholinesterase and concentration of dextran sulphate precipitable lipoproteins, cholesterol and triglycerides was observed in sixteen children with a diagnosis of nephrotic syndrome when compared with the values obtained in 22 other normal children of comparable ages. 2. In 7 children with nephrotic syndrome serum concentrations of beta-lipoprotein and cholinesterase were markedly higher in the acute stage compared to the convalescent stage. A working hypothesis is proposed to explain the hyperlipoproteinemia in nephrotic syndrome.", "contents": "Relationship between serum cholinesterase and low density lipoproteins in children with nephrotic syndrome. 1. A significant increase in the activity of serum cholinesterase and concentration of dextran sulphate precipitable lipoproteins, cholesterol and triglycerides was observed in sixteen children with a diagnosis of nephrotic syndrome when compared with the values obtained in 22 other normal children of comparable ages. 2. In 7 children with nephrotic syndrome serum concentrations of beta-lipoprotein and cholinesterase were markedly higher in the acute stage compared to the convalescent stage. A working hypothesis is proposed to explain the hyperlipoproteinemia in nephrotic syndrome."} {"id": "PMID:165017", "title": "Composition of low-density lipoprotein in children with hyperlipoproteinaemia.", "content": "Low-density lipoprotein composition, studied in 7 pre-pubertal children with secondary hyperlipoproteinaemia, did not differ significantly from that found in 12 normal children. This contrasts with the findings in 12 children with the heterozygous form of familial hypercholesterolaemia in whom the low-density lipoprotein was significantly deficient in triglyceride (p smaller than 0.001) and protein (p smaller than 0.025), and had an increased proportion of cholesterol esters compared with normal (p greater than 0.01). Treatment which lowered serum cholesterol and low-density lipoprotein concentration in these children did not materially alter the abnormalities of composition of the low-density lipoprotein. The data support the hypothesis that an abnormality of composition of low-density lipoprotein is an integral feature of familial hypercholesterolaemia and does not simply result from an increased concentration of low-density lipoprotein of whatever cause.", "contents": "Composition of low-density lipoprotein in children with hyperlipoproteinaemia. Low-density lipoprotein composition, studied in 7 pre-pubertal children with secondary hyperlipoproteinaemia, did not differ significantly from that found in 12 normal children. This contrasts with the findings in 12 children with the heterozygous form of familial hypercholesterolaemia in whom the low-density lipoprotein was significantly deficient in triglyceride (p smaller than 0.001) and protein (p smaller than 0.025), and had an increased proportion of cholesterol esters compared with normal (p greater than 0.01). Treatment which lowered serum cholesterol and low-density lipoprotein concentration in these children did not materially alter the abnormalities of composition of the low-density lipoprotein. The data support the hypothesis that an abnormality of composition of low-density lipoprotein is an integral feature of familial hypercholesterolaemia and does not simply result from an increased concentration of low-density lipoprotein of whatever cause."} {"id": "PMID:165018", "title": "Hexokinase isozyme pattern in CCl(4)-injured rat liver.", "content": "Activities of hexokinase isozymes in carbon tetrachloride (CCl(4))-injured rat liver were determined quantitatively by DEAE-cellulose column chromatography and compared with those of regenerating liver, fetal liver and ascites hepatoma cells (AH 130). The CCl(4)-injured liver revealed an isozyme distribution with predominant Types I, II and III (3.2, 8.8 and 6.8 times higher than the control values, respectively) and with undetectable activity of Type IV hexokinase (glucokinase). Although the isozyme pattern generally resembled that of fetal liver or hepatoma cells, the relatively high activity of hexokinase Type III in CCl(4) treatment characterizes the pattern of hexokinase isozyme in acue liver damage.", "contents": "Hexokinase isozyme pattern in CCl(4)-injured rat liver. Activities of hexokinase isozymes in carbon tetrachloride (CCl(4))-injured rat liver were determined quantitatively by DEAE-cellulose column chromatography and compared with those of regenerating liver, fetal liver and ascites hepatoma cells (AH 130). The CCl(4)-injured liver revealed an isozyme distribution with predominant Types I, II and III (3.2, 8.8 and 6.8 times higher than the control values, respectively) and with undetectable activity of Type IV hexokinase (glucokinase). Although the isozyme pattern generally resembled that of fetal liver or hepatoma cells, the relatively high activity of hexokinase Type III in CCl(4) treatment characterizes the pattern of hexokinase isozyme in acue liver damage."} {"id": "PMID:165019", "title": "Determination of human liver cytochrome P-450 by electron paramagnetic resonance of liver biopsies.", "content": "Human liver cytochrome P-450 level has beenen determined by direct electron paramagnetic resonance spectroscopy at 77 degrees K of liver specimens obtained by surgical biopsy. A preliminary experiment with rat livers was performed in order to calibrate the intensity of the cytochrome P-450 EPR signal as a function of the cytochrome concentration obtained by the classical spectrophotometric method. 44 subjects have be examined. We found a cytochrome P-450 value of 21.5 plus or minus 11.2 nmoles per gram of liver in normal subjects. Variations of this level in some pathological liver states are discussed.", "contents": "Determination of human liver cytochrome P-450 by electron paramagnetic resonance of liver biopsies. Human liver cytochrome P-450 level has beenen determined by direct electron paramagnetic resonance spectroscopy at 77 degrees K of liver specimens obtained by surgical biopsy. A preliminary experiment with rat livers was performed in order to calibrate the intensity of the cytochrome P-450 EPR signal as a function of the cytochrome concentration obtained by the classical spectrophotometric method. 44 subjects have be examined. We found a cytochrome P-450 value of 21.5 plus or minus 11.2 nmoles per gram of liver in normal subjects. Variations of this level in some pathological liver states are discussed."} {"id": "PMID:165020", "title": "Human very low density lipoproteins: loss of electrophoretic mobility on enzymatic removal of sialic acid residues.", "content": "Incubation of very low density lipoproteins (VLDL) from three hyperlipoproteinemic patients with neuraminidase resulted in a progressive liberation of sialic acid residues. After the original sialic content had been reduced by approx. 75% a lipoprotein fraction having zero electrophoretic mobility on paper appeared. This fraction increased until, after the removal of all the sialic acid residues, the mobility of the entire VLDL fraction was reduced to zero.", "contents": "Human very low density lipoproteins: loss of electrophoretic mobility on enzymatic removal of sialic acid residues. Incubation of very low density lipoproteins (VLDL) from three hyperlipoproteinemic patients with neuraminidase resulted in a progressive liberation of sialic acid residues. After the original sialic content had been reduced by approx. 75% a lipoprotein fraction having zero electrophoretic mobility on paper appeared. This fraction increased until, after the removal of all the sialic acid residues, the mobility of the entire VLDL fraction was reduced to zero."} {"id": "PMID:165021", "title": "Viral hepatitis and cirrhosis.", "content": "Most of the knowledge of post-hepatitic cirrhosis comes from studies performed in the last five years on the hepatitis B antigen-related variety. The position of other types of hepatitis (particularly type A) as an aetiological factor in cirrhosis remains conjectural. In general, the post-hepatitic cirrhosis develops insidiously after a mild or unrecognised acute episode of hepatitis. General progress is slow. Early deaths are due to liver failure. Later, primary hepatocellular carcinoma assumes increasing importance. Needle biopsy of the liver is usually necessary to confirm the diagnosis of cirrhosis and to estimate the degree of activity. Sampling errors when such a small specimen of liver is obtained must be taken into account, when formulating a diagnosis and prognosis. Prednisolone therapy is usually given if the patient is symptomatic, biochemical tests are abnormal and the liver biopsy confirms active chronic hepatitis with or without cirrhosis. The evidence of benefit is not so strong as for other forms of active hepatitis and cirrhosis such as the lupoid type. The management of the cirrhosis is otherwise along orthodox lines.", "contents": "Viral hepatitis and cirrhosis. Most of the knowledge of post-hepatitic cirrhosis comes from studies performed in the last five years on the hepatitis B antigen-related variety. The position of other types of hepatitis (particularly type A) as an aetiological factor in cirrhosis remains conjectural. In general, the post-hepatitic cirrhosis develops insidiously after a mild or unrecognised acute episode of hepatitis. General progress is slow. Early deaths are due to liver failure. Later, primary hepatocellular carcinoma assumes increasing importance. Needle biopsy of the liver is usually necessary to confirm the diagnosis of cirrhosis and to estimate the degree of activity. Sampling errors when such a small specimen of liver is obtained must be taken into account, when formulating a diagnosis and prognosis. Prednisolone therapy is usually given if the patient is symptomatic, biochemical tests are abnormal and the liver biopsy confirms active chronic hepatitis with or without cirrhosis. The evidence of benefit is not so strong as for other forms of active hepatitis and cirrhosis such as the lupoid type. The management of the cirrhosis is otherwise along orthodox lines."} {"id": "PMID:165022", "title": "Lp(a) lipoprotein/pre-beta1-lipoprotein in Swedish middle-aged males and in patients with coronary heart disease.", "content": "A strong, positive association (P smaller than 0.0001) was found between the presence in serum of pre-beta1-lipoprotein upon electrophoresis in 0.5% agarose and the Lp(a+) phenotype in a series of 103 males aged 50-52 years participating in a health control study and in a series of 58 patients with sustained myocardial infarction. Both lipiprotein phenomena were more prevalent in the 58 patients than in the 103 presumably healthy males. The lack of any significant difference between total cholesterol values in the patients and the controls, despite the higher frequency of phenotype Lp(a+) in the former group, argues against the suggestion by Walton et al. (1974) that the increased Lp(a+) frequency in patients with coronary artery disease may be caused by a general increase in the concentration of low density lipoproteins (LDL).", "contents": "Lp(a) lipoprotein/pre-beta1-lipoprotein in Swedish middle-aged males and in patients with coronary heart disease. A strong, positive association (P smaller than 0.0001) was found between the presence in serum of pre-beta1-lipoprotein upon electrophoresis in 0.5% agarose and the Lp(a+) phenotype in a series of 103 males aged 50-52 years participating in a health control study and in a series of 58 patients with sustained myocardial infarction. Both lipiprotein phenomena were more prevalent in the 58 patients than in the 103 presumably healthy males. The lack of any significant difference between total cholesterol values in the patients and the controls, despite the higher frequency of phenotype Lp(a+) in the former group, argues against the suggestion by Walton et al. (1974) that the increased Lp(a+) frequency in patients with coronary artery disease may be caused by a general increase in the concentration of low density lipoproteins (LDL)."} {"id": "PMID:165024", "title": "Growth following renal transplantation in children and adolescents.", "content": "Growth following renal transplantation in children and adolescents. Sixteen children who received a cadaveric renal transplant surviving 1 to 5 years, had their growth rate assessed while receiving 10 to 25 mg of prednisone every 48 hours. Six of 9 patients witha a bone age of 12 years or less grew at a \"normal\" rate. None of the patients whose bone age was greater than 12 years grew at a \"normal\" rate. Since low-dose alternate-day prednisone therapy allows for optimal growth but does not appear to compromise kidney survival, we feel such a regime should be instituted in growing children receiving a kidney transplant.", "contents": "Growth following renal transplantation in children and adolescents. Growth following renal transplantation in children and adolescents. Sixteen children who received a cadaveric renal transplant surviving 1 to 5 years, had their growth rate assessed while receiving 10 to 25 mg of prednisone every 48 hours. Six of 9 patients witha a bone age of 12 years or less grew at a \"normal\" rate. None of the patients whose bone age was greater than 12 years grew at a \"normal\" rate. Since low-dose alternate-day prednisone therapy allows for optimal growth but does not appear to compromise kidney survival, we feel such a regime should be instituted in growing children receiving a kidney transplant."} {"id": "PMID:165029", "title": "Dose-response to tibric acid: a new hypolipidemic drug in type IV hyperlipoproteinemia.", "content": "This double-blind study compares the effects of tibric acid at four different doses to that of placebo in type IV hyperlipidemic patients. Fifty patients, divided at random in five groups of 10 patients each, received one of the following treatments: placebo, tibric acid 500 mg, 750 mg, 1,000 mg, or 1,250 mg per 24 hr. The data suggest that the 1,000 mg and the 1,250 mg doses are effective in lowering the serum triglyceride levels after 6 wk of treatment; the effect on total cholesterol is less pronouced. No effect is observed on the concentration of serum esterified cholesterol, phospholipids, and free fatty acids. It is also shown that in the dose range studied, the best fitting curve defining the four mean values of triglycerides and total cholesterol obtained with the four active treatments did not deviate significantly from linearity. Due to lack of toxicity, tibric acid may be useful in the treatment of type IV hyperlipoproteinemia.", "contents": "Dose-response to tibric acid: a new hypolipidemic drug in type IV hyperlipoproteinemia. This double-blind study compares the effects of tibric acid at four different doses to that of placebo in type IV hyperlipidemic patients. Fifty patients, divided at random in five groups of 10 patients each, received one of the following treatments: placebo, tibric acid 500 mg, 750 mg, 1,000 mg, or 1,250 mg per 24 hr. The data suggest that the 1,000 mg and the 1,250 mg doses are effective in lowering the serum triglyceride levels after 6 wk of treatment; the effect on total cholesterol is less pronouced. No effect is observed on the concentration of serum esterified cholesterol, phospholipids, and free fatty acids. It is also shown that in the dose range studied, the best fitting curve defining the four mean values of triglycerides and total cholesterol obtained with the four active treatments did not deviate significantly from linearity. Due to lack of toxicity, tibric acid may be useful in the treatment of type IV hyperlipoproteinemia."} {"id": "PMID:165025", "title": "Observations on embryonic chick-bone crystals by high resolution transmission electron microscopy.", "content": "High resolution transmission electron microscopy of bone mineral at a vary early stage in its deposition in embryonic chick frontal bone demonstrates crystals of 2-2.5 nm thickness and a profile up to 40 nm long. They appear in groups which may show as few as one or two crystals. Associated with the crystals is a less dense amorphous material. Using specimen tilting, the change in crystal appearance indicates that crystals are tablet-shaped (rectangular) rather than rod-shaped. The amorphous material may be tablet-shaped crystals in orientations which are not dense enough to register as crystals in the image. Truly amorphous mineral does not show by bright-field electron microscopy, but preliminary results indicate that the dark-field technique may prove to be useful in imaging amorphous mineral provided that sections can be cut thinly enough and that precautions are taken during specimen preparation to avoid mineral loss. Crystals have been located in various parts of the osteoid zone and were not associated specifically with any one component. Rapid processing using anhydrous techniques must be used to avoid the possibility of artefactually altering the in vivo conditions of the mineral at the time of excision of the specimen.", "contents": "Observations on embryonic chick-bone crystals by high resolution transmission electron microscopy. High resolution transmission electron microscopy of bone mineral at a vary early stage in its deposition in embryonic chick frontal bone demonstrates crystals of 2-2.5 nm thickness and a profile up to 40 nm long. They appear in groups which may show as few as one or two crystals. Associated with the crystals is a less dense amorphous material. Using specimen tilting, the change in crystal appearance indicates that crystals are tablet-shaped (rectangular) rather than rod-shaped. The amorphous material may be tablet-shaped crystals in orientations which are not dense enough to register as crystals in the image. Truly amorphous mineral does not show by bright-field electron microscopy, but preliminary results indicate that the dark-field technique may prove to be useful in imaging amorphous mineral provided that sections can be cut thinly enough and that precautions are taken during specimen preparation to avoid mineral loss. Crystals have been located in various parts of the osteoid zone and were not associated specifically with any one component. Rapid processing using anhydrous techniques must be used to avoid the possibility of artefactually altering the in vivo conditions of the mineral at the time of excision of the specimen."} {"id": "PMID:165026", "title": "Calcium accumulation by chondrocyte mitochondria.", "content": "Chick epiphyseal plate mitochondria observed in vitro suggest that energy dependent Ca++ uptake was maximal in the presence of ATP and a respiratory substrate. However, nucleotides other than ATP had no effect on this type of cation uptake. The observation that Ca++ accumulation was sensitive to the presence of 2,4-DNP and a number of respiratory inhibitors suggested that the mechanism of cation accumulation was similar to that described in tissues that do not undergo biological mineralization. Non-energy supported Ca++ acumulation was studied in the presence of rotenone and antimycin A. Under these conditions, the amount of Ca++ bound by skeletal tissue mitochondria was greater than bound by mitochondria obtained from noncalcifying tissues. Following isopycnic centrifugation, the Ca++ loaded mitochondria banded at different sucrose densties but the Ca++ affinity of mitochondria at each density band was similar. Hence, no particular mitochondrial species seems to be responsible for cation transport.", "contents": "Calcium accumulation by chondrocyte mitochondria. Chick epiphyseal plate mitochondria observed in vitro suggest that energy dependent Ca++ uptake was maximal in the presence of ATP and a respiratory substrate. However, nucleotides other than ATP had no effect on this type of cation uptake. The observation that Ca++ accumulation was sensitive to the presence of 2,4-DNP and a number of respiratory inhibitors suggested that the mechanism of cation accumulation was similar to that described in tissues that do not undergo biological mineralization. Non-energy supported Ca++ acumulation was studied in the presence of rotenone and antimycin A. Under these conditions, the amount of Ca++ bound by skeletal tissue mitochondria was greater than bound by mitochondria obtained from noncalcifying tissues. Following isopycnic centrifugation, the Ca++ loaded mitochondria banded at different sucrose densties but the Ca++ affinity of mitochondria at each density band was similar. Hence, no particular mitochondrial species seems to be responsible for cation transport."} {"id": "PMID:165030", "title": "Enzyme activities and properties of lysosomes and brush borders in jejunal biopsies from control subjects and patients with coeliac disease.", "content": "1. Reduced activities of four enzymes from brush borders were found in intestianl biopsies from patients with untreated coeliac disease. The activities returned towards control values after treatment by gluten withdrawal. Parallel changes were noted for the cytosol enzyme lactate dehydrogenase. 2. Measurement of brush-border integrity by differential centrifugation of biopsy extracts indicated increased fragility of the brush borders in biopsies from untreated patients. Normal values were obtained for biopsies from treated patients. 3. Increased activites of six acid hydrolases (lysosomal enzymes) were found in biopsies from untreated coeliac patients. Normal values were obtained for biopsies from treated patients. 4. Assement of lysosomal integrity by assay of latent N-acetyl-beta-glucosaminidase and of sedimentable activity of four acid hydrolases demonstrated increased lysosomal fragility in untreated coeliac mucosa. These lysosomal changes return to within the normal range after treatment by gluten withdrawal. 5. The lysosomal changes are consistent with their having a pathogenic role in the enterocyte damage of coeliac disease. Possible mechanisms for the lysosomal changes are discussed.", "contents": "Enzyme activities and properties of lysosomes and brush borders in jejunal biopsies from control subjects and patients with coeliac disease. 1. Reduced activities of four enzymes from brush borders were found in intestianl biopsies from patients with untreated coeliac disease. The activities returned towards control values after treatment by gluten withdrawal. Parallel changes were noted for the cytosol enzyme lactate dehydrogenase. 2. Measurement of brush-border integrity by differential centrifugation of biopsy extracts indicated increased fragility of the brush borders in biopsies from untreated patients. Normal values were obtained for biopsies from treated patients. 3. Increased activites of six acid hydrolases (lysosomal enzymes) were found in biopsies from untreated coeliac patients. Normal values were obtained for biopsies from treated patients. 4. Assement of lysosomal integrity by assay of latent N-acetyl-beta-glucosaminidase and of sedimentable activity of four acid hydrolases demonstrated increased lysosomal fragility in untreated coeliac mucosa. These lysosomal changes return to within the normal range after treatment by gluten withdrawal. 5. The lysosomal changes are consistent with their having a pathogenic role in the enterocyte damage of coeliac disease. Possible mechanisms for the lysosomal changes are discussed."} {"id": "PMID:165031", "title": "Vitamin D metabolism and parathyroid function in man.", "content": "1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone.", "contents": "Vitamin D metabolism and parathyroid function in man. 1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone."} {"id": "PMID:165037", "title": "Persistent papillomatosis associated with immunodeficiency.", "content": "A case report of a young bull with persistent papillomatosis associated with immunodeficiency is presented. Humoral immune responses were normal but cell mediated immunity was deficient. The possible significance of the findings to pathogenesis and therapy of the disease is discussed.", "contents": "Persistent papillomatosis associated with immunodeficiency. A case report of a young bull with persistent papillomatosis associated with immunodeficiency is presented. Humoral immune responses were normal but cell mediated immunity was deficient. The possible significance of the findings to pathogenesis and therapy of the disease is discussed."} {"id": "PMID:165044", "title": "Transbronchial forceps lung biopsy through the fiberoptic bronchoscope. tdiagnosis of diffuse pulmonary disease.", "content": "Transbronchial forceps biopsy through the fiberoptic bronchoscope was performed in 37 patients. Tissue was technically inadequate for examination in two cases. A pathologic diagnosis was obtained in 26 (72 percent) and in five additional critically ill patients, direct histologic examination of lung tissue allowed exclusion of certain entities, thus significantly influencing therapy. Overall, the procedure was of value in 31 of 35 patients (90 percent). There was no significant hemorrhage and there was one 15 percent pneumothorax. The safety and high diagnostic yield of this technique in the diagnosis of diffuse lung disease is proved.", "contents": "Transbronchial forceps lung biopsy through the fiberoptic bronchoscope. tdiagnosis of diffuse pulmonary disease. Transbronchial forceps biopsy through the fiberoptic bronchoscope was performed in 37 patients. Tissue was technically inadequate for examination in two cases. A pathologic diagnosis was obtained in 26 (72 percent) and in five additional critically ill patients, direct histologic examination of lung tissue allowed exclusion of certain entities, thus significantly influencing therapy. Overall, the procedure was of value in 31 of 35 patients (90 percent). There was no significant hemorrhage and there was one 15 percent pneumothorax. The safety and high diagnostic yield of this technique in the diagnosis of diffuse lung disease is proved."} {"id": "PMID:165045", "title": "Cyclophosphamide, vincristine and sequential split-course radiotherapy in the treatment of small cell lung cancer.", "content": "Thirty-nine patients with small cell lung cancer were treated with large dose intravenous cyclophosphamide combined with vincristine. Sequential split-course radiotherapy was added when the gross disease was limited to one hemithorax and draining scalene nodes. Fifteen of 16 patients in the limited disease category showed objective response, eight of which were complete. Fourteen of 23 patients in the extensive disease category yielded an objective response, six of which were complete. The median survival for complete responders was 48 weeks, 38 weeks for partial responders and 14 weeks for non-responders. The difference between responders and non-responders was statistically significant. The major toxicity was myelosuppression with a median leukocyte nadir of 500/mm-3 noted on treatment day no. 15. Prompt recovery was the rule. Toxicity appeared to be cumulative for patients receiving radiotherapy. These results are superior to those evolving from treatment with cyclophosphamide as a solitary agent.", "contents": "Cyclophosphamide, vincristine and sequential split-course radiotherapy in the treatment of small cell lung cancer. Thirty-nine patients with small cell lung cancer were treated with large dose intravenous cyclophosphamide combined with vincristine. Sequential split-course radiotherapy was added when the gross disease was limited to one hemithorax and draining scalene nodes. Fifteen of 16 patients in the limited disease category showed objective response, eight of which were complete. Fourteen of 23 patients in the extensive disease category yielded an objective response, six of which were complete. The median survival for complete responders was 48 weeks, 38 weeks for partial responders and 14 weeks for non-responders. The difference between responders and non-responders was statistically significant. The major toxicity was myelosuppression with a median leukocyte nadir of 500/mm-3 noted on treatment day no. 15. Prompt recovery was the rule. Toxicity appeared to be cumulative for patients receiving radiotherapy. These results are superior to those evolving from treatment with cyclophosphamide as a solitary agent."} {"id": "PMID:165047", "title": "Colorectal cancer in children: epidemiologic aspects.", "content": "Despite many similarities to colorectal cancer in adults, the rare childhood form has some peculiarities. Childhood mortality is greater among Negroes than Caucasians, particularly in boys, reflecting the rising incidence of this tumor in the young Negro population. In addition, the percentage of childhood cases with precancerous diseases (polyposis, colitis) appears greater than in adults. Most striking is the high percentage of mucin-producing tumors in young people with colorectal cancer. The mucoid tumors tend to occur after the age of 10 years, whereas younger children are more likely to develop non-mucoid carcinoma in an adenomatous polyp.", "contents": "Colorectal cancer in children: epidemiologic aspects. Despite many similarities to colorectal cancer in adults, the rare childhood form has some peculiarities. Childhood mortality is greater among Negroes than Caucasians, particularly in boys, reflecting the rising incidence of this tumor in the young Negro population. In addition, the percentage of childhood cases with precancerous diseases (polyposis, colitis) appears greater than in adults. Most striking is the high percentage of mucin-producing tumors in young people with colorectal cancer. The mucoid tumors tend to occur after the age of 10 years, whereas younger children are more likely to develop non-mucoid carcinoma in an adenomatous polyp."} {"id": "PMID:165048", "title": "Adenocarcinoma arising in a diverticular abscess of the colon: report of a case.", "content": "A case of a patient with adenocarcinoma in an abscess cavity that resulted from perforated diverticulitis of the descending colon is described. Serial barium-enema studies over a nine-year period show the diverticulosis, perforation, abscess cavity, and finally the adenocarcinoma in the abscess cavity. Although it is infrequent, the possibility of carcinoma must be considered in cases of patients who have unhealed pericolonic abscess cavities.", "contents": "Adenocarcinoma arising in a diverticular abscess of the colon: report of a case. A case of a patient with adenocarcinoma in an abscess cavity that resulted from perforated diverticulitis of the descending colon is described. Serial barium-enema studies over a nine-year period show the diverticulosis, perforation, abscess cavity, and finally the adenocarcinoma in the abscess cavity. Although it is infrequent, the possibility of carcinoma must be considered in cases of patients who have unhealed pericolonic abscess cavities."} {"id": "PMID:165049", "title": "Metastasis from a pedunculated adenomatous colonic polyp with focally invasive carcinoma: report of a case.", "content": "A patient who had metastasis from a focus of invasive carcinoma confined to the head of an otherwise benign pedunculated adenomatous polyp of the sigmoid colon is described. That only 20 such cases have been reported previously attests to the rarity of this phenomenon. Because the morbidity and mortality of radical surgery far outweigh the liklihood of metastasis from such foci of invasive carcinoma in pedunculated adenomatous colonic polyps, local removal is recommended.", "contents": "Metastasis from a pedunculated adenomatous colonic polyp with focally invasive carcinoma: report of a case. A patient who had metastasis from a focus of invasive carcinoma confined to the head of an otherwise benign pedunculated adenomatous polyp of the sigmoid colon is described. That only 20 such cases have been reported previously attests to the rarity of this phenomenon. Because the morbidity and mortality of radical surgery far outweigh the liklihood of metastasis from such foci of invasive carcinoma in pedunculated adenomatous colonic polyps, local removal is recommended."} {"id": "PMID:165054", "title": "[Paroxysmal ACTH secretion from an adrenal medullary tumour (author's transl)].", "content": "A secondary Cushing's syndrome developed in a 38-year-old woman from an ACTH secreting phaeochromocytoma. Large amounts of ACTH were demonstrated in the tumour by radioimmunological tests. A remarkable feature was that clinical and biochemical signs of increased catecholamine secretion completely regressed with time and the adrenals were stimulated at intervals by the ectopic ACTH secretion, steroid excretion falling to normal in between.", "contents": "[Paroxysmal ACTH secretion from an adrenal medullary tumour (author's transl)]. A secondary Cushing's syndrome developed in a 38-year-old woman from an ACTH secreting phaeochromocytoma. Large amounts of ACTH were demonstrated in the tumour by radioimmunological tests. A remarkable feature was that clinical and biochemical signs of increased catecholamine secretion completely regressed with time and the adrenals were stimulated at intervals by the ectopic ACTH secretion, steroid excretion falling to normal in between."} {"id": "PMID:165055", "title": "Investigations upon adenohypophysial cell proliferation in vitro: influence of oestradiol, thyrotropin releasing hormone, dibutyryl cyclic AMP and theophylline.", "content": "Mitotic indices were counted in adenohypophysial fragments cultured in vitromthe cultures exposed to 17-beta oestradiol, synthetic thyrotropin releasing hormone (TRH) and dibutyryl cyclic AMP showed a higher number of mitoses as compared with respective controls. However, theophylline decreased the mitotic index in cultured adenohypophysis.", "contents": "Investigations upon adenohypophysial cell proliferation in vitro: influence of oestradiol, thyrotropin releasing hormone, dibutyryl cyclic AMP and theophylline. Mitotic indices were counted in adenohypophysial fragments cultured in vitromthe cultures exposed to 17-beta oestradiol, synthetic thyrotropin releasing hormone (TRH) and dibutyryl cyclic AMP showed a higher number of mitoses as compared with respective controls. However, theophylline decreased the mitotic index in cultured adenohypophysis."} {"id": "PMID:165056", "title": "Lipolysis and cyclic-3', 5'-AMP content in rat adipose tissue at different age.", "content": "The content of cAMP, the release of glycerol and nonesterified fatty acids (NEFA) of adipose tissue with and without the stimulation by ACTH and norepinephrine were determined in young and old rats. After the lipid mobilizing hormones lowered concentration of cAMP and impaired stimulation of lipolytic activity were found in old rats. Furthermore, less stimulation of glycerol and NEFA release by cAMP was observed in these animals. These results suggested that in old animals a lower lipolytic activity per tissue and lipid mass is available in intact and hormone stimulated fat tissue and therefore the accumulation of lipids in fat depots is facilitated.", "contents": "Lipolysis and cyclic-3', 5'-AMP content in rat adipose tissue at different age. The content of cAMP, the release of glycerol and nonesterified fatty acids (NEFA) of adipose tissue with and without the stimulation by ACTH and norepinephrine were determined in young and old rats. After the lipid mobilizing hormones lowered concentration of cAMP and impaired stimulation of lipolytic activity were found in old rats. Furthermore, less stimulation of glycerol and NEFA release by cAMP was observed in these animals. These results suggested that in old animals a lower lipolytic activity per tissue and lipid mass is available in intact and hormone stimulated fat tissue and therefore the accumulation of lipids in fat depots is facilitated."} {"id": "PMID:165057", "title": "Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and brain.", "content": "In vivo studies of the exchange of tracer [125-I]-L-triiodothyronine (T3) between plasma (P), and the anterior pituitary (AP), posterior pituitary (PP), median eminence (ME) and the frontal lobes of the brain (B), in the rat show that from 2.5 h onwards the concentration of new [125I]T3 in AP, PP and B were parellel to that of the plasma, with a t1/2 of 7.4 h; the t1/2 for ME was 10.3 h. The extrapolation of these curves to zero time was assumed to indicate the relative concentration of T3 per unit weight in terms of total body T3. T3 content of these tissues was determined by radioimmunoassay. The values obtained validated the steady state parameters derived from the radio-isotopic measurements. As an indicator of the concentration gradient between tissue and plasma the organ/plasma (O/P) ratio was calculated; these data indicate that under steady state conditions, the order of T3 concentration is AP greater than PP greater than ME greater than B. Binding studies have shown that AP and PP contain \"specific,\" saturable binders while ME and B do not. Evaluation of the binding parameters of the high affinity binders in both AP and PP gave similar association constants. These associations constants, when corrected for the binding strength of T3 to plasma proteins, resulted in values similar to those of neuclear T3 binders.", "contents": "Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and brain. In vivo studies of the exchange of tracer [125-I]-L-triiodothyronine (T3) between plasma (P), and the anterior pituitary (AP), posterior pituitary (PP), median eminence (ME) and the frontal lobes of the brain (B), in the rat show that from 2.5 h onwards the concentration of new [125I]T3 in AP, PP and B were parellel to that of the plasma, with a t1/2 of 7.4 h; the t1/2 for ME was 10.3 h. The extrapolation of these curves to zero time was assumed to indicate the relative concentration of T3 per unit weight in terms of total body T3. T3 content of these tissues was determined by radioimmunoassay. The values obtained validated the steady state parameters derived from the radio-isotopic measurements. As an indicator of the concentration gradient between tissue and plasma the organ/plasma (O/P) ratio was calculated; these data indicate that under steady state conditions, the order of T3 concentration is AP greater than PP greater than ME greater than B. Binding studies have shown that AP and PP contain \"specific,\" saturable binders while ME and B do not. Evaluation of the binding parameters of the high affinity binders in both AP and PP gave similar association constants. These associations constants, when corrected for the binding strength of T3 to plasma proteins, resulted in values similar to those of neuclear T3 binders."} {"id": "PMID:165058", "title": "Effect of insulin and lipolytic hormones on cyclic AMP phosphodieterase activity in normal and diabetic rat adipose tissue.", "content": "Insulin has been shown to lower cyclic AMP (cAMP) levels in hormonally sensitive tissue. The mechanism by which this lowering occurs has not yet been fully defined. We studied the effects of insulin on rat adipose tissue cyclic nucleotide phosphodiestrase (PDE) in an incubation system. The adipose tissue used was from both normal animals and animals rendered diabetic by intravenous injections of streptozotocin. Rat epididymal fat pads were incubated in a Krebs-Ringer bicarbonate-4% albumin system with O, 100, 1,000 or 10,000 PU/ml insulin (INS); epinephrine (EPI) or glucagon (GLU) at several different concentrations. After 15 min of incubation, each tissue was homogenized, centrifugated, and the supernatant assayed for cAMP PDE activity using the breakdown of (3-H)cAMP. The data was used to characterize cAMP PDE into apparent high and low K-m PDE components. In the normal animals, INS increased Vmax of the low Km PDE components; 100 pU/ml INS, 30%, 1000 p1/ML INS, 40; and 10,000 pU/ml INS, 20%. In contrast, streptoxotocin diabetes lowered this Vmax by 30%. In the diabetic animals, INS also increased Vmax by 30%. In the diabetic animals, INS also increased Vmax of the low Km PDE component; 100 pU/ml INS, 30%; 1000 pU/ml INS, 50% and 10,000 pU/ml INS, 100%. Epinephrine at 1, 10, and 100 pg/ml stimulated low Km cAMP PDE activity by 67%, 73% and 44% respectively. The stimulatory effect of EPI on both the low and high Km cAMP PDE activity was neutralized by propranolol or adenosine. In comparison to EPI, GLU at very low concentrations, 10-9M, stimulated low Km cAMP PDE. These studies suggest that some of the biologic actions of insulin, an antilipolytic substance, are mediated through activation of low Km PDE. Furthermore, this enzymatic activity is lower in experimental diabetes. The stimulation of low Km PDE by lipolytic hormones may reflect a long-range protective action of these agents.", "contents": "Effect of insulin and lipolytic hormones on cyclic AMP phosphodieterase activity in normal and diabetic rat adipose tissue. Insulin has been shown to lower cyclic AMP (cAMP) levels in hormonally sensitive tissue. The mechanism by which this lowering occurs has not yet been fully defined. We studied the effects of insulin on rat adipose tissue cyclic nucleotide phosphodiestrase (PDE) in an incubation system. The adipose tissue used was from both normal animals and animals rendered diabetic by intravenous injections of streptozotocin. Rat epididymal fat pads were incubated in a Krebs-Ringer bicarbonate-4% albumin system with O, 100, 1,000 or 10,000 PU/ml insulin (INS); epinephrine (EPI) or glucagon (GLU) at several different concentrations. After 15 min of incubation, each tissue was homogenized, centrifugated, and the supernatant assayed for cAMP PDE activity using the breakdown of (3-H)cAMP. The data was used to characterize cAMP PDE into apparent high and low K-m PDE components. In the normal animals, INS increased Vmax of the low Km PDE components; 100 pU/ml INS, 30%, 1000 p1/ML INS, 40; and 10,000 pU/ml INS, 20%. In contrast, streptoxotocin diabetes lowered this Vmax by 30%. In the diabetic animals, INS also increased Vmax by 30%. In the diabetic animals, INS also increased Vmax of the low Km PDE component; 100 pU/ml INS, 30%; 1000 pU/ml INS, 50% and 10,000 pU/ml INS, 100%. Epinephrine at 1, 10, and 100 pg/ml stimulated low Km cAMP PDE activity by 67%, 73% and 44% respectively. The stimulatory effect of EPI on both the low and high Km cAMP PDE activity was neutralized by propranolol or adenosine. In comparison to EPI, GLU at very low concentrations, 10-9M, stimulated low Km cAMP PDE. These studies suggest that some of the biologic actions of insulin, an antilipolytic substance, are mediated through activation of low Km PDE. Furthermore, this enzymatic activity is lower in experimental diabetes. The stimulation of low Km PDE by lipolytic hormones may reflect a long-range protective action of these agents."} {"id": "PMID:165059", "title": "Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat.", "content": "We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH.", "contents": "Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat. We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH."} {"id": "PMID:165060", "title": "Bioactive and immunoactive ACTH in the rat pituitary: influence of stress and adrenalectomy.", "content": "Tissue levels of bioactive and immunoactive ACTH were measured in both the anterior and neuro-intermediate lobes of the rat pituitary. Similar concentrations of bioactive (65 ng/mg) and immunoactive (83 ng/mg) ACTH were found in the anterior lobes control rats. A 2-min ether stress had no effect on either bioactive or immunoactive ACTH levels in the anterior lobe. Twenty-four h after adrenalectomy the anterior lobe content of both bioactive and immunoactive ACTH decreased only to return to supranormal levels 21 days after the operation. A 30-min neurogenic stress had no effect on anterior lobe bioactive ACTH content but reduced the immunoactive ACTH level to 50 ng/mg. Synthetic alphah-17-39 ACTH was used in our radio-immunoassay in order to measure the C-terminal ACTH activity of the neuro-intermediate lobe. The concentration of such C-terminal activity in control rats (890 ng alphah-17-39 ACTH/mg) considerably exceeded the amount of bioactive ACTH (15 ng/mg). This is presumably due primarily to the presence of the so-called corticotropin-like intermediate lobe-peptide (CLIP). The amounts of bioactive or C-terminal immunoactive ACTH in the neuro-intermediate lobe were not affected by ether stress nor short term (24-h) or long term (21-day) adrenalectomy. Neuro-intermediate lobe bioactive ACTH decreased (to 8 ng/mg) only with the introduction of a 30-min neurogenic stress. Neurogenic stress had no effect on the concentration of CLIP, but when the stress was imposed 24 h after adrenalectomy, a significant reduction was observed. The data support the presence of bioactive ACTH in the intermediate lobe of the rat pituitary and suggest that such ACTH is preferentially released by neurogenic stress and not appreciably regulated by circulating levels of glucocorticoids. Until the biological function and/or target organ of CLIP is identified, the significance of the changes in tissue levels of C-terminal immunoactive ACTH will remain unknown.", "contents": "Bioactive and immunoactive ACTH in the rat pituitary: influence of stress and adrenalectomy. Tissue levels of bioactive and immunoactive ACTH were measured in both the anterior and neuro-intermediate lobes of the rat pituitary. Similar concentrations of bioactive (65 ng/mg) and immunoactive (83 ng/mg) ACTH were found in the anterior lobes control rats. A 2-min ether stress had no effect on either bioactive or immunoactive ACTH levels in the anterior lobe. Twenty-four h after adrenalectomy the anterior lobe content of both bioactive and immunoactive ACTH decreased only to return to supranormal levels 21 days after the operation. A 30-min neurogenic stress had no effect on anterior lobe bioactive ACTH content but reduced the immunoactive ACTH level to 50 ng/mg. Synthetic alphah-17-39 ACTH was used in our radio-immunoassay in order to measure the C-terminal ACTH activity of the neuro-intermediate lobe. The concentration of such C-terminal activity in control rats (890 ng alphah-17-39 ACTH/mg) considerably exceeded the amount of bioactive ACTH (15 ng/mg). This is presumably due primarily to the presence of the so-called corticotropin-like intermediate lobe-peptide (CLIP). The amounts of bioactive or C-terminal immunoactive ACTH in the neuro-intermediate lobe were not affected by ether stress nor short term (24-h) or long term (21-day) adrenalectomy. Neuro-intermediate lobe bioactive ACTH decreased (to 8 ng/mg) only with the introduction of a 30-min neurogenic stress. Neurogenic stress had no effect on the concentration of CLIP, but when the stress was imposed 24 h after adrenalectomy, a significant reduction was observed. The data support the presence of bioactive ACTH in the intermediate lobe of the rat pituitary and suggest that such ACTH is preferentially released by neurogenic stress and not appreciably regulated by circulating levels of glucocorticoids. Until the biological function and/or target organ of CLIP is identified, the significance of the changes in tissue levels of C-terminal immunoactive ACTH will remain unknown."} {"id": "PMID:165061", "title": "The effect of stress on the cytology and immunocytochemistry of pars intermedia cells in the rat pituitary.", "content": "The purpose of this study was to determine if there were ultrastructural and immunocytochemical changes in intermediate lobe cells following stress. We found marked cytological changes in intermediate lobe cells after 30 min of stress with a buzzer and stroboscopic light (neurogenic). Following such treatment, the cytoplasm was filled with pale graules or empty vesicles. There was cytological evidence of increased secretory and synthetic activity. Innunocytochemical staining (for 17-39-ATCH) revelaed that there were fewer stained granules per cell in such rats although the individual granules stained as strongly as those in control rats. No cytological changes were observed following ether stress. These results correlated well with our bioassay and radioimmunoassay data which showed that only neurogenic stress resulted in depletion of ACTH from neuro-intermediate lobes (1). In agreement with the work of others, we found no obvious cytological changes in intermediate lobes from adrenalectomized or cortisol treated rats wheras anterior lobe ACTH cells hypertrophied following adrenalectomy and involuted following cortisol treatment. Anterior lobe ACTH cells from intact rats showed no degranulation following 30 min of buzzer stress or after 2 min of ether stress.", "contents": "The effect of stress on the cytology and immunocytochemistry of pars intermedia cells in the rat pituitary. The purpose of this study was to determine if there were ultrastructural and immunocytochemical changes in intermediate lobe cells following stress. We found marked cytological changes in intermediate lobe cells after 30 min of stress with a buzzer and stroboscopic light (neurogenic). Following such treatment, the cytoplasm was filled with pale graules or empty vesicles. There was cytological evidence of increased secretory and synthetic activity. Innunocytochemical staining (for 17-39-ATCH) revelaed that there were fewer stained granules per cell in such rats although the individual granules stained as strongly as those in control rats. No cytological changes were observed following ether stress. These results correlated well with our bioassay and radioimmunoassay data which showed that only neurogenic stress resulted in depletion of ACTH from neuro-intermediate lobes (1). In agreement with the work of others, we found no obvious cytological changes in intermediate lobes from adrenalectomized or cortisol treated rats wheras anterior lobe ACTH cells hypertrophied following adrenalectomy and involuted following cortisol treatment. Anterior lobe ACTH cells from intact rats showed no degranulation following 30 min of buzzer stress or after 2 min of ether stress."} {"id": "PMID:165062", "title": "Autoradiographic localization of radioactivity from [3-H]oxytocin in the rat mammary gland and oviduct.", "content": "[3-H]Oxytocin was incubated in vitro with pieces of oviduct and mammary gland and the tissue were subjected to autoradiography. Radioactivity was localized only in smooth muscle cells of the oviduct and in regions of mammary tissue where myoepithelial cells are found. In contrast, radioactivity was not concentrated in any region of skeletal muscle, a nontarget tissue for oxytocin. The localization of radioactivity in oviduct and mammary cells was absent when the tissues were incubated with [3-H]oxytocin and an excess of unlabeled oxytocin. These findings provide evidence for the presence of specific and high affinity receptors for oxytocin in its target tissues.", "contents": "Autoradiographic localization of radioactivity from [3-H]oxytocin in the rat mammary gland and oviduct. [3-H]Oxytocin was incubated in vitro with pieces of oviduct and mammary gland and the tissue were subjected to autoradiography. Radioactivity was localized only in smooth muscle cells of the oviduct and in regions of mammary tissue where myoepithelial cells are found. In contrast, radioactivity was not concentrated in any region of skeletal muscle, a nontarget tissue for oxytocin. The localization of radioactivity in oviduct and mammary cells was absent when the tissues were incubated with [3-H]oxytocin and an excess of unlabeled oxytocin. These findings provide evidence for the presence of specific and high affinity receptors for oxytocin in its target tissues."} {"id": "PMID:165063", "title": "Effects of age and obesity on insulin binding to isolated adipocytes.", "content": "We have measured insulin binding to isolated adipocytes prepared from rats of varying ages and body weights. The ability of adipocytes to bind insulin progressively decreases as animals get older and fatter until about 70 days of age and 300 g body weight are reached. From this point on further decreases in insulin binding to adipocytes were not seen as rats got older and fatter. Analysis of the data indicated that this decrease in insulin binding could be accounted for by decreased numbers of insulin receptor sites per cell. Further studies were conducted in which animals were allowed to age, but obesity was prevented or reversed by hypocaloric diets. In these experiments decreased insulin binding was either prevented or restored to normal by the negative caloric state, indicating that age had no appreciable effect on the ability of adipocytes to bind insulin. The influence of the obesity associated variables-hyperinsulinemia and increased fat cell size-on insulin binding was also examined. These latter studies are consistent with the concept that elevated in vivo plasma insulin levels lead to decreased insulin receptors, and further suggest a role for additonal factors in regulating the adipocyte insulin receptor. 1. Decreased insulin binding to adipocytes is closely related to the obese state. 2. This decrease in insulin binding can be accounted for by decreased numbers of receptor sites per cell, and 3. The mecahnism(s) underlying this decreased insulin binding are complex and probably represents an effect of more than one variable.", "contents": "Effects of age and obesity on insulin binding to isolated adipocytes. We have measured insulin binding to isolated adipocytes prepared from rats of varying ages and body weights. The ability of adipocytes to bind insulin progressively decreases as animals get older and fatter until about 70 days of age and 300 g body weight are reached. From this point on further decreases in insulin binding to adipocytes were not seen as rats got older and fatter. Analysis of the data indicated that this decrease in insulin binding could be accounted for by decreased numbers of insulin receptor sites per cell. Further studies were conducted in which animals were allowed to age, but obesity was prevented or reversed by hypocaloric diets. In these experiments decreased insulin binding was either prevented or restored to normal by the negative caloric state, indicating that age had no appreciable effect on the ability of adipocytes to bind insulin. The influence of the obesity associated variables-hyperinsulinemia and increased fat cell size-on insulin binding was also examined. These latter studies are consistent with the concept that elevated in vivo plasma insulin levels lead to decreased insulin receptors, and further suggest a role for additonal factors in regulating the adipocyte insulin receptor. 1. Decreased insulin binding to adipocytes is closely related to the obese state. 2. This decrease in insulin binding can be accounted for by decreased numbers of receptor sites per cell, and 3. The mecahnism(s) underlying this decreased insulin binding are complex and probably represents an effect of more than one variable."} {"id": "PMID:165064", "title": "Specific binding sites for natural glucocorticoids in plasma membranes of rat liver.", "content": "The presence of sites specifically binding natural glucocortocoids in plasma membrane (PM) preparations (PM0, density=1.13-1.16; PM1, density=1.16-1.18) from rat liver was elucidated by equilibrium dialysis as well as by centrifugal methods. Equilibrium dialysis showed the presence of binding sites having a higher affinity for [3-H]cortisol (Kd=1.4 times 10- minus 9M at 4C) in PM0, and that of the binding sites having a lower affinity for [3H] cortisol (Kd=1.3 times 10- minus 8M at 4C) in PM1, while centrifugal analysis showed the presence of higher affinity binding sites (Kd=1.5-1.9 times 10- minus 97 at 0 C) in both PM0 and PM1, and also of intermediate affinity binding sites (Kd=4.1 times 10- minus 9M at 0 C) in PM1. The discrepancy in the cortisol binding parameters obtained by the two different methods seems to be due mainly to the lability of some binding sites, especially the PM1. The glucocorticoid-binding sites in the plasma membranes of rat liver appear to have the highest affinity of corticosterone, followed by cortisol and cortisone. A synthetic glucocorticoid [3H]-dexamethasone, did not show any specific binding to the liver plasma membranes. Neither dexamethasone nor nonglucocorticoids such as estradiol given simultaneously affected [3H] cortisol binding to the plasma membranes.", "contents": "Specific binding sites for natural glucocorticoids in plasma membranes of rat liver. The presence of sites specifically binding natural glucocortocoids in plasma membrane (PM) preparations (PM0, density=1.13-1.16; PM1, density=1.16-1.18) from rat liver was elucidated by equilibrium dialysis as well as by centrifugal methods. Equilibrium dialysis showed the presence of binding sites having a higher affinity for [3-H]cortisol (Kd=1.4 times 10- minus 9M at 4C) in PM0, and that of the binding sites having a lower affinity for [3H] cortisol (Kd=1.3 times 10- minus 8M at 4C) in PM1, while centrifugal analysis showed the presence of higher affinity binding sites (Kd=1.5-1.9 times 10- minus 97 at 0 C) in both PM0 and PM1, and also of intermediate affinity binding sites (Kd=4.1 times 10- minus 9M at 0 C) in PM1. The discrepancy in the cortisol binding parameters obtained by the two different methods seems to be due mainly to the lability of some binding sites, especially the PM1. The glucocorticoid-binding sites in the plasma membranes of rat liver appear to have the highest affinity of corticosterone, followed by cortisol and cortisone. A synthetic glucocorticoid [3H]-dexamethasone, did not show any specific binding to the liver plasma membranes. Neither dexamethasone nor nonglucocorticoids such as estradiol given simultaneously affected [3H] cortisol binding to the plasma membranes."} {"id": "PMID:165065", "title": "Studies on inhibition of TSH stimulation of adenyl cyclase activity in thyroid plasma membrane preparations by propranolol.", "content": "Propranolol (1 mM) was found to inhibit TSH stimulation of adenyl cyclase activity in a subcellular fraction from bovine thyroid enriched in plasma membranes. However, stimulation due to PGE1 or NaF was not similarly inhibited. Since (i) and inhibition was observed at concentrations of propranolol between 10-minus 4 and 10- minus 3M, and appeared to be noncompetitive (ii) the optical isomers of propranolol were equipotent, (iii) inhibition was specific for propranolol since it was not observed with the closely related drug practolol (1 mM), and (iv) quinidine (1 mM) and the local anaesthetics lignocaine and aptocaine also proved inhibitory, we concluded that propranolol inhibition of TSH stimulation was due to its \"quinidine-like\" properties (i.e., relatively specific and characteristic membrane-active properties) and not to its action as a beta-adrenergic antagonist.", "contents": "Studies on inhibition of TSH stimulation of adenyl cyclase activity in thyroid plasma membrane preparations by propranolol. Propranolol (1 mM) was found to inhibit TSH stimulation of adenyl cyclase activity in a subcellular fraction from bovine thyroid enriched in plasma membranes. However, stimulation due to PGE1 or NaF was not similarly inhibited. Since (i) and inhibition was observed at concentrations of propranolol between 10-minus 4 and 10- minus 3M, and appeared to be noncompetitive (ii) the optical isomers of propranolol were equipotent, (iii) inhibition was specific for propranolol since it was not observed with the closely related drug practolol (1 mM), and (iv) quinidine (1 mM) and the local anaesthetics lignocaine and aptocaine also proved inhibitory, we concluded that propranolol inhibition of TSH stimulation was due to its \"quinidine-like\" properties (i.e., relatively specific and characteristic membrane-active properties) and not to its action as a beta-adrenergic antagonist."} {"id": "PMID:165066", "title": "Hydrolysis of estrogen conjugates by the lungs of the dog in vivo.", "content": "Although hydrolysis of certain estrogen conjugates released into the systemic circulation is now known to occur in the human and in the dog, the site or sites of such hydrolysis remained unidentified. In an attempt to identify such sites, radioactive estrone was infused intravenously into a series of male dogs and serial paired samples of blood were obtained from the right ventricle (RV) and a peripheral artery (A). The samples were analysed for total radioactivity, unconjugated radioactive estrogens, radioactive estrone, estradiol-17beta, estrone sulfate, estrone glucosiduronate and estradiol-17beta glucosiduronate(s). The mean percent extraction across the lungs (see article) was calculated for each radioactive moiety analyzed. There was no significant percent extration of total radioactivity or of estrone sulfate. The mean percent extractions for unconjugated estrogens and for estrone and estradiol-17beta were -24.7, -21 and -34.3 respectively (P less than 0.01), indicating net production by the lungs. The mean percent extractions for estrone glucosiduronate and estradiol-17beta glucosiduronate(s) were +19.8 and +10.0 respectively (P less then 0.01), indicating net uptake of these conjugates by the lungs. Statistical analysis showed that the two processes were related. Our findings support the hypothesis that the lungs are one site, possibly the main site, at which hydrolysis of estrogen glucosiduronates occurs in the dog.", "contents": "Hydrolysis of estrogen conjugates by the lungs of the dog in vivo. Although hydrolysis of certain estrogen conjugates released into the systemic circulation is now known to occur in the human and in the dog, the site or sites of such hydrolysis remained unidentified. In an attempt to identify such sites, radioactive estrone was infused intravenously into a series of male dogs and serial paired samples of blood were obtained from the right ventricle (RV) and a peripheral artery (A). The samples were analysed for total radioactivity, unconjugated radioactive estrogens, radioactive estrone, estradiol-17beta, estrone sulfate, estrone glucosiduronate and estradiol-17beta glucosiduronate(s). The mean percent extraction across the lungs (see article) was calculated for each radioactive moiety analyzed. There was no significant percent extration of total radioactivity or of estrone sulfate. The mean percent extractions for unconjugated estrogens and for estrone and estradiol-17beta were -24.7, -21 and -34.3 respectively (P less than 0.01), indicating net production by the lungs. The mean percent extractions for estrone glucosiduronate and estradiol-17beta glucosiduronate(s) were +19.8 and +10.0 respectively (P less then 0.01), indicating net uptake of these conjugates by the lungs. Statistical analysis showed that the two processes were related. Our findings support the hypothesis that the lungs are one site, possibly the main site, at which hydrolysis of estrogen glucosiduronates occurs in the dog."} {"id": "PMID:165067", "title": "Anterior pituitary hormone release in vitro inversely related to extracellular osmolarity.", "content": "Release of hormones from bovine anterior pituitary tissue in vitro was inveresly related to the osmolarity of the incubation medium. Addition of each of several ionic or non-ionic solutes to Krebs-Ringer-bicarbonate (KRB) or to beef serum inhibited hormone release. If the value of 286 mOsm/liter of KRB is considered as 100%, the osmolarity of the medium was altered from -15% to +10% of control. Over this range, an increase in osmolarity of 10% resulted in the following percentage inhibition: ACTH, 47; PRL, 43; TSH, 36; LH, 23; GH, 18; maximal percentage inhibition over this range was as follows: ACTH, 80; PRL, 60; TSH, 60; LH, 45; GH, 40. The inverse relationship between extracellular oxmolarity and secretion of ACTH and PRL would appear to be appropriate in view of the salt and water retaining actions of these hormones. The sensitivity of the response to osmotic changes suggests a possible role of body osmolarity in the regulation of adenohypophysial secretion.", "contents": "Anterior pituitary hormone release in vitro inversely related to extracellular osmolarity. Release of hormones from bovine anterior pituitary tissue in vitro was inveresly related to the osmolarity of the incubation medium. Addition of each of several ionic or non-ionic solutes to Krebs-Ringer-bicarbonate (KRB) or to beef serum inhibited hormone release. If the value of 286 mOsm/liter of KRB is considered as 100%, the osmolarity of the medium was altered from -15% to +10% of control. Over this range, an increase in osmolarity of 10% resulted in the following percentage inhibition: ACTH, 47; PRL, 43; TSH, 36; LH, 23; GH, 18; maximal percentage inhibition over this range was as follows: ACTH, 80; PRL, 60; TSH, 60; LH, 45; GH, 40. The inverse relationship between extracellular oxmolarity and secretion of ACTH and PRL would appear to be appropriate in view of the salt and water retaining actions of these hormones. The sensitivity of the response to osmotic changes suggests a possible role of body osmolarity in the regulation of adenohypophysial secretion."} {"id": "PMID:165068", "title": "Effect of dexamethasone on the secretion of thyrotropin in the rat: dose and time relations.", "content": "Serum TSH and corticosterone concentrations were measured in intact rats and in rats given TRH or exposed to short-term cold 3 h and 12 h after pretreatment with dexamethasone in various doses. Dexamethasone given 3 h before experiemtns significantly depressed both TRH- and cold-induced TSH responses at all dose levels. Dose of 25 pg/100 g body weight significantly depressed serum TSH concentration when given 3 h before the experiment. However, when given 12 h before the experiment the drug augmented TRH-induced TSH secretion, although the cold response was unaltered. In intact rats dexamethasone significantly depressed serum TSH concentration in doses of 250 and 500 mug/100 g body weight. In all experiments the steroid blocked ACTH secretion. These results support the view that the effect of dexamethasone on thyroid function is highly dependent on the time relations. A single large dose of dexamethasone has first an inhibitory effect at the pituitary level and then facilitates pituitary to TRH and at the same time inhibits secretion of TRH in response to cold.", "contents": "Effect of dexamethasone on the secretion of thyrotropin in the rat: dose and time relations. Serum TSH and corticosterone concentrations were measured in intact rats and in rats given TRH or exposed to short-term cold 3 h and 12 h after pretreatment with dexamethasone in various doses. Dexamethasone given 3 h before experiemtns significantly depressed both TRH- and cold-induced TSH responses at all dose levels. Dose of 25 pg/100 g body weight significantly depressed serum TSH concentration when given 3 h before the experiment. However, when given 12 h before the experiment the drug augmented TRH-induced TSH secretion, although the cold response was unaltered. In intact rats dexamethasone significantly depressed serum TSH concentration in doses of 250 and 500 mug/100 g body weight. In all experiments the steroid blocked ACTH secretion. These results support the view that the effect of dexamethasone on thyroid function is highly dependent on the time relations. A single large dose of dexamethasone has first an inhibitory effect at the pituitary level and then facilitates pituitary to TRH and at the same time inhibits secretion of TRH in response to cold."} {"id": "PMID:165069", "title": "Evidence for persistent binding of biologically active thyrotropin to thyroid in vitro.", "content": "Differences exist in the rates at which hormones are inactivated by, or dissociate from, their target tissues. The present studies examined the binding of biologically active TSH to thyroid slices and compared its characteristics to those of PGE. Canine thyroid slices were initally incubated with 5 mU/ML OF BOVINE TSH (TSH-Inital) for 15 min, washed and incubated in media free of hormone for 3 hr. At the conclusion of this second incubation period all slices were again washed. Some were then transferred to media containing 10-2M theophylline for a final 10 min incubation and subsequent measurement of cAMP and protein kinase, while others were transferred to media containing (l-14C)glucose without theophylline for a final 45 min incubation to assess glucose oxidation. Identically treated slices never exposed to TSH served as controls, while others were exposed to TSH only during the final 10 or 45 min incubation periods (TSH-Final). cAMP content determined after significantly increased in TSH-Initial (mean 2.98 plus or minus 0.36 (se) pmol/mg wet wt) compared to control (0.35 plus or minus 0.04), but was less than that in TSH-Final (5.76 plus or minus 0.51). This phenomenon was not unique to canine thyroid, since comparable results were noted in studies of human, bovine or porcine thyroid slices. The protein kinase activity ratio (-cAMP/+cAMP) and glucose oxidation of TSH-Initial were also significantly increased above control following the final 10 min or 45 min incubations respectively. Addition of trypsin to the 3 h incubation abolished the subsequent increase in cAMP in TSH-Initial, while addition of TSH antiserum appreciably reduced this increase. These results are consistent with the persistent binding of biologically active TSH to thyroid. By contrast, evidence of similar persistent binding of PGE1 to thyroid, glucagon to liver, or parathyroid hormone to renal cortex was lacking when assessed by an identical experimental procedure. Differences between the duration of interaction of TSH and PGE1 with thyroid may be dependent or a more gradual dissociation to tissue bound TSH, a more rapid inactivation of bound-PGE1, or both.", "contents": "Evidence for persistent binding of biologically active thyrotropin to thyroid in vitro. Differences exist in the rates at which hormones are inactivated by, or dissociate from, their target tissues. The present studies examined the binding of biologically active TSH to thyroid slices and compared its characteristics to those of PGE. Canine thyroid slices were initally incubated with 5 mU/ML OF BOVINE TSH (TSH-Inital) for 15 min, washed and incubated in media free of hormone for 3 hr. At the conclusion of this second incubation period all slices were again washed. Some were then transferred to media containing 10-2M theophylline for a final 10 min incubation and subsequent measurement of cAMP and protein kinase, while others were transferred to media containing (l-14C)glucose without theophylline for a final 45 min incubation to assess glucose oxidation. Identically treated slices never exposed to TSH served as controls, while others were exposed to TSH only during the final 10 or 45 min incubation periods (TSH-Final). cAMP content determined after significantly increased in TSH-Initial (mean 2.98 plus or minus 0.36 (se) pmol/mg wet wt) compared to control (0.35 plus or minus 0.04), but was less than that in TSH-Final (5.76 plus or minus 0.51). This phenomenon was not unique to canine thyroid, since comparable results were noted in studies of human, bovine or porcine thyroid slices. The protein kinase activity ratio (-cAMP/+cAMP) and glucose oxidation of TSH-Initial were also significantly increased above control following the final 10 min or 45 min incubations respectively. Addition of trypsin to the 3 h incubation abolished the subsequent increase in cAMP in TSH-Initial, while addition of TSH antiserum appreciably reduced this increase. These results are consistent with the persistent binding of biologically active TSH to thyroid. By contrast, evidence of similar persistent binding of PGE1 to thyroid, glucagon to liver, or parathyroid hormone to renal cortex was lacking when assessed by an identical experimental procedure. Differences between the duration of interaction of TSH and PGE1 with thyroid may be dependent or a more gradual dissociation to tissue bound TSH, a more rapid inactivation of bound-PGE1, or both."} {"id": "PMID:165070", "title": "Effect of temperature during preparation of rat adrenal quarters and isolated cell suspension of their ACTH responsiveness.", "content": "The effect of temperature during preparation of rat adrenal quarters or isolated adrenal cell suspension on their response to ACTH was examined through a comparison of amounts of corticosterone produced after their incubation. The response to ACTH added in vitro was considerably higher when adrenal quarters and isolated adrenal cell suspension were prepared at room temperature (25 degree C) than when prepared at ice-cold. Endogenous steroidogenesis was not affected by the temperature. It seemed unlikely that this higher response to ACTH of adrenal quarters or isolated adrenal cell suspension prepared at room temperature was due to an activation of the cells. A possibility was discussed that cooling adrenal quarters or isolated adrenal cell suspension during the preparation may create an unphysiological state in some place to related the cell membrane.", "contents": "Effect of temperature during preparation of rat adrenal quarters and isolated cell suspension of their ACTH responsiveness. The effect of temperature during preparation of rat adrenal quarters or isolated adrenal cell suspension on their response to ACTH was examined through a comparison of amounts of corticosterone produced after their incubation. The response to ACTH added in vitro was considerably higher when adrenal quarters and isolated adrenal cell suspension were prepared at room temperature (25 degree C) than when prepared at ice-cold. Endogenous steroidogenesis was not affected by the temperature. It seemed unlikely that this higher response to ACTH of adrenal quarters or isolated adrenal cell suspension prepared at room temperature was due to an activation of the cells. A possibility was discussed that cooling adrenal quarters or isolated adrenal cell suspension during the preparation may create an unphysiological state in some place to related the cell membrane."} {"id": "PMID:165071", "title": "Inhibitory effect of ouabain on epinephrine-induced stimulation of adrenal corticosterone secretion in rats.", "content": "Chronic administration of ouabain (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) definitely inhibited epinephrine-induced increase of adrenal corticosterone secretion. The inhibition rate increased along with frequency of ouabain administration. Increase in adrenal corticosterone synthesis and secretion by ACTH (20-50 mU/rat) administration was partially suppressed by pretreatment with chronic ouabain administration. A slight but significant increase of adrenal corticosterone secretion caused by epinephrine administration in hypophysectomized rats was also inhibited by pretreatment with ouabain administration. Chronic administration of neither phentolamine (1 mg/rat, intraperitoneally, once daily for consecutive 15 days) nor propranolol (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) caused significant changes in adrenal corticosterone secretion in response to ACTH as well as to epinephrine. Chronic administration of ouabain in rats causes not only elevated secretion of ACTH from anterior pituitary but also functional change in adrenals leading to suppression of corticosterone secretion in response to ACTH or epinephrine administration.", "contents": "Inhibitory effect of ouabain on epinephrine-induced stimulation of adrenal corticosterone secretion in rats. Chronic administration of ouabain (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) definitely inhibited epinephrine-induced increase of adrenal corticosterone secretion. The inhibition rate increased along with frequency of ouabain administration. Increase in adrenal corticosterone synthesis and secretion by ACTH (20-50 mU/rat) administration was partially suppressed by pretreatment with chronic ouabain administration. A slight but significant increase of adrenal corticosterone secretion caused by epinephrine administration in hypophysectomized rats was also inhibited by pretreatment with ouabain administration. Chronic administration of neither phentolamine (1 mg/rat, intraperitoneally, once daily for consecutive 15 days) nor propranolol (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) caused significant changes in adrenal corticosterone secretion in response to ACTH as well as to epinephrine. Chronic administration of ouabain in rats causes not only elevated secretion of ACTH from anterior pituitary but also functional change in adrenals leading to suppression of corticosterone secretion in response to ACTH or epinephrine administration."} {"id": "PMID:165072", "title": "Effect of triiodothyronine or iodide on the thyroidal secretion in vitro: Inhibition of TSH- and dibutyryl-cyclic-AMP induced endocytosis.", "content": "T3 or iodide, at the concentration of 10- minus 3M, inhibits TSH- or dibutyryl-cyclic AMP-induced thyroidal intracellular colloid droplet formation, while leaving the TSH-induced increase in cyclic AMP levels intact. The effect of T3 appeared not to be mediated through the iodide derived from deiodination of T3. Those results clearly demonstrate that T3 or iodide acts at the point beyond cyclic AMP generation and prior tothe formation of intracellular colloid droplets. This is also the site at which microtubule active reagents exert their influence. Whether T3 or iodide fits this category or acts in as yet undetermined manner remains to be established.", "contents": "Effect of triiodothyronine or iodide on the thyroidal secretion in vitro: Inhibition of TSH- and dibutyryl-cyclic-AMP induced endocytosis. T3 or iodide, at the concentration of 10- minus 3M, inhibits TSH- or dibutyryl-cyclic AMP-induced thyroidal intracellular colloid droplet formation, while leaving the TSH-induced increase in cyclic AMP levels intact. The effect of T3 appeared not to be mediated through the iodide derived from deiodination of T3. Those results clearly demonstrate that T3 or iodide acts at the point beyond cyclic AMP generation and prior tothe formation of intracellular colloid droplets. This is also the site at which microtubule active reagents exert their influence. Whether T3 or iodide fits this category or acts in as yet undetermined manner remains to be established."} {"id": "PMID:165073", "title": "Changes in enzyme activity in human trichinosis.", "content": "Changes in enzyme activity in human trichinosis have been studied. The activities of 19 enzymes and some isoenzymes were investigated in 12 patients from the 3rd to the 20th week. The activities of muscle-specific enzymes (CK, ALD and MK) were greatly increased with peaks during the 4th week; activities returned to normal ranges during the 7th and 8th weeks. Liver-specific enzymes (GTP, OCT, guanase, GLDH, SDH and MDH) and AP, ChE, cerulosplasmin remained within normal limits in all patients with the exception of a child who died. An explanation of the origin of hyperenzymemia is proposed on the basis of these investigations. The data obtained support the proposition that hyperenzymemia is of muscular origin and that the liver is seldom affected in case of trichinosis.", "contents": "Changes in enzyme activity in human trichinosis. Changes in enzyme activity in human trichinosis have been studied. The activities of 19 enzymes and some isoenzymes were investigated in 12 patients from the 3rd to the 20th week. The activities of muscle-specific enzymes (CK, ALD and MK) were greatly increased with peaks during the 4th week; activities returned to normal ranges during the 7th and 8th weeks. Liver-specific enzymes (GTP, OCT, guanase, GLDH, SDH and MDH) and AP, ChE, cerulosplasmin remained within normal limits in all patients with the exception of a child who died. An explanation of the origin of hyperenzymemia is proposed on the basis of these investigations. The data obtained support the proposition that hyperenzymemia is of muscular origin and that the liver is seldom affected in case of trichinosis."} {"id": "PMID:165074", "title": "Properties of enzymes. V. Catalase inhibition of glucose oxidase reaction.", "content": "The radical produced aerobically in the glucose oxidase reaction reduces the oxidated cytochrome c. The extent of reduction depends on the concentrations of substrate (glucose) and enzyme. Superoxide dismutase purified from various sources does not inhibit the cytochrome c reduction, but catalase does, in proportion to its concentration. This inhibition, which might be utilized for quantitative catalase determinations, provides further evidence for the formation of H2O2 in the glucose oxidase reaction.", "contents": "Properties of enzymes. V. Catalase inhibition of glucose oxidase reaction. The radical produced aerobically in the glucose oxidase reaction reduces the oxidated cytochrome c. The extent of reduction depends on the concentrations of substrate (glucose) and enzyme. Superoxide dismutase purified from various sources does not inhibit the cytochrome c reduction, but catalase does, in proportion to its concentration. This inhibition, which might be utilized for quantitative catalase determinations, provides further evidence for the formation of H2O2 in the glucose oxidase reaction."} {"id": "PMID:165075", "title": "Cyclic AMP phosphodiesterase activity in three Morris hepatomas.", "content": "Rat liver cAMP phosphodiesterase has been fractionated into four peaks of activity with isoelectrofocusing column chromatography. The major two liver peaks (high Km enzymes) decreased with increasing growth rate while the minor two liver peaks (low Km enzymes) increased in one fast growing Morris hepatoma. There was also less total phosphodiesterase activity in the fast growing hepatoma.", "contents": "Cyclic AMP phosphodiesterase activity in three Morris hepatomas. Rat liver cAMP phosphodiesterase has been fractionated into four peaks of activity with isoelectrofocusing column chromatography. The major two liver peaks (high Km enzymes) decreased with increasing growth rate while the minor two liver peaks (low Km enzymes) increased in one fast growing Morris hepatoma. There was also less total phosphodiesterase activity in the fast growing hepatoma."} {"id": "PMID:165076", "title": "Differential effects of metal-binding agents on the D-glucose-6-phosphate phosphohydrolase activity of the rat liver.", "content": "The metal-binding agents (citrate, oxalate, bicarbonate, EDTA) exert dual effects on D-glucose-6-phosphate phosphohydrolase activity in the homogenate as well as in the subcellular fractions. The important differences of the effects are associated with the concentration of the chelator and with time of its addition. The small (appropriate) concentrations of the metal-binding agents stimulate and stabilize the enzyme activity. However, chelators used in higher concentrations exert the inhibitory influence on the activity of glucose-6-phosphatase. Stimulation of the reaction was observed only if the chelator was added before the enzyme-substrate complex formation has been started. The formation of the ternary complex: the enzyme(metal)-chelator substrate exerting a protective influence on the active centre has been suggested. The hypothesis of a similar action of the metal-binding agents and Pi on the glucose-6-phosphatase as a metaloproteid has been proposed.", "contents": "Differential effects of metal-binding agents on the D-glucose-6-phosphate phosphohydrolase activity of the rat liver. The metal-binding agents (citrate, oxalate, bicarbonate, EDTA) exert dual effects on D-glucose-6-phosphate phosphohydrolase activity in the homogenate as well as in the subcellular fractions. The important differences of the effects are associated with the concentration of the chelator and with time of its addition. The small (appropriate) concentrations of the metal-binding agents stimulate and stabilize the enzyme activity. However, chelators used in higher concentrations exert the inhibitory influence on the activity of glucose-6-phosphatase. Stimulation of the reaction was observed only if the chelator was added before the enzyme-substrate complex formation has been started. The formation of the ternary complex: the enzyme(metal)-chelator substrate exerting a protective influence on the active centre has been suggested. The hypothesis of a similar action of the metal-binding agents and Pi on the glucose-6-phosphatase as a metaloproteid has been proposed."} {"id": "PMID:165077", "title": "Carbohydrate content and regulation following injection of different glycogenolytic enzymes.", "content": "The effect of injection of glycogenolytic enzymes on tissue glycogen, blood glucose and plasma insulin was studied in mice. No effects were observed following phosphorylase, whereas the hydrolytic enzymes, alpha-amylase and acid amyloglucosidase depressed liver glycogen. In addition acid amyloglucosidase induced a decrease in blood glucose, a slight elevation of plasma insulin and a marked increase in tolbutamide-stimulated insulin release. At the doses given none of the enzymes affected muscle glycogen. Amyloglucosidase pretreatment markedly enhanced insulin release induced by glibenclamide, leucine, isoleucine, lysine and glucose whereas insulin release stimulated by IPNA, ACTH, glucagon and \"CCK-PZ\" was unaffected. Injection of acid amyloglucosidase has a profound influence on carbohydrate content and regulation in mice. It is suggested that the dependence or independence of amyloglucosidase activity among the insulin secretagogues tested might reflect different or partially different mechanisms in the process of insulin secretion.", "contents": "Carbohydrate content and regulation following injection of different glycogenolytic enzymes. The effect of injection of glycogenolytic enzymes on tissue glycogen, blood glucose and plasma insulin was studied in mice. No effects were observed following phosphorylase, whereas the hydrolytic enzymes, alpha-amylase and acid amyloglucosidase depressed liver glycogen. In addition acid amyloglucosidase induced a decrease in blood glucose, a slight elevation of plasma insulin and a marked increase in tolbutamide-stimulated insulin release. At the doses given none of the enzymes affected muscle glycogen. Amyloglucosidase pretreatment markedly enhanced insulin release induced by glibenclamide, leucine, isoleucine, lysine and glucose whereas insulin release stimulated by IPNA, ACTH, glucagon and \"CCK-PZ\" was unaffected. Injection of acid amyloglucosidase has a profound influence on carbohydrate content and regulation in mice. It is suggested that the dependence or independence of amyloglucosidase activity among the insulin secretagogues tested might reflect different or partially different mechanisms in the process of insulin secretion."} {"id": "PMID:165078", "title": "Conformational studies of equilibrium structures in fragments of horse heart cytochrome c.", "content": "Ultraviolet absorption and circular dichroism studies have been carried out on horse heart apo-cytochrome c and heme-free peptide fragments obtained by cyanogen bromide cleavage of the native protein. It was noted that the various peptides assume predominantly an unordered conformation in water solution. Increasing ionic strength and addition of 2-chloroethanol increase the right-handed helical content. Guanidinium hydrochloride favors the coil state. It was also demonstrated that two non-interacting helical regions of different stability are present in the apo-protein in 2-chloroethanol.", "contents": "Conformational studies of equilibrium structures in fragments of horse heart cytochrome c. Ultraviolet absorption and circular dichroism studies have been carried out on horse heart apo-cytochrome c and heme-free peptide fragments obtained by cyanogen bromide cleavage of the native protein. It was noted that the various peptides assume predominantly an unordered conformation in water solution. Increasing ionic strength and addition of 2-chloroethanol increase the right-handed helical content. Guanidinium hydrochloride favors the coil state. It was also demonstrated that two non-interacting helical regions of different stability are present in the apo-protein in 2-chloroethanol."} {"id": "PMID:165079", "title": "Action of rheumatoid synovial collagenase on cartilage collagen. Different susceptibilities of cartilage and tendon collagen to collagenase attack.", "content": "The action of purified rheumatoid synovial collagenase on purified cartilage collagen, alpha-1(II)-3, in solution at 25 degrees C has been characterised. The enzyme attacked cartilage collagen in solution producing a 58% reduction in specific viscosity and resulting in the appearance of two reaction products which represented approximately three-quarter and one-quarter fragments of the intact molecule as shown by disc electrophoresis in polyacrylamide gels containing sodium dodecyl sulphate. The alpha-chain fragments which comprised each of these components corresponded to molecular weights of approximately 74000 and 21000. Electron microscopy of segment-long-spacing crystallites of the reaction products revealed three-quarter (TC-a) and one-quarter (TC-b) length fragments, and permitted accurate localization of the cleavage locus between bands 41 and 42 (I-41). This cleavage site and the formation of TC-a and TC-b reaction products are very similar to those found for type-I collagen substrates. Cartilage collagen in solution was found to be more resistant to collagenase attack than tendon collagen, the rate of cartilage collagen degradation being six times slower than that for tendon collagen, as judged by viscometry. The mid-point melting temperatures (T-m) for lathyritic cartilage and tendon collagen were 40.5 and 41.5 degrees C, and for the collagenase-produced reaction products 38.5 and 37.5 degrees C, respectively. The significance of these findings is discussed in relation to the structure of type I and II collagens.", "contents": "Action of rheumatoid synovial collagenase on cartilage collagen. Different susceptibilities of cartilage and tendon collagen to collagenase attack. The action of purified rheumatoid synovial collagenase on purified cartilage collagen, alpha-1(II)-3, in solution at 25 degrees C has been characterised. The enzyme attacked cartilage collagen in solution producing a 58% reduction in specific viscosity and resulting in the appearance of two reaction products which represented approximately three-quarter and one-quarter fragments of the intact molecule as shown by disc electrophoresis in polyacrylamide gels containing sodium dodecyl sulphate. The alpha-chain fragments which comprised each of these components corresponded to molecular weights of approximately 74000 and 21000. Electron microscopy of segment-long-spacing crystallites of the reaction products revealed three-quarter (TC-a) and one-quarter (TC-b) length fragments, and permitted accurate localization of the cleavage locus between bands 41 and 42 (I-41). This cleavage site and the formation of TC-a and TC-b reaction products are very similar to those found for type-I collagen substrates. Cartilage collagen in solution was found to be more resistant to collagenase attack than tendon collagen, the rate of cartilage collagen degradation being six times slower than that for tendon collagen, as judged by viscometry. The mid-point melting temperatures (T-m) for lathyritic cartilage and tendon collagen were 40.5 and 41.5 degrees C, and for the collagenase-produced reaction products 38.5 and 37.5 degrees C, respectively. The significance of these findings is discussed in relation to the structure of type I and II collagens."} {"id": "PMID:165080", "title": "Drainage of thoracic duct lymph in twelve patients with myasthenia gravis.", "content": "The effect of thoracic duct lymph drainage (5-34 days) in 12 patients with myasthenia gravis on muscular function has been followed for 5-43 months. Among the results obtained were: (1) During the drainage the myasthenic symptoms decreased markedly after 1-4 days and remained so during the drainage. (2) The doses of cholinesterase inhibitors had to be markedly reduced during the lymph drainage in eight patients. (3) Discontinuation of the lymph drainage increased the myasthenic symptoms within a few days. However, after a median observation time of 14 months with conventional treatment all but one of the patients had improved. (4) Retransfusion of the patients own cell-free lymph caused a worsening of the myasthenic symptoms. This effect could also be obtained following infusion of IgG preparations from the patients lymph. Three retransfusions of cell suspensions obtained from the thoracic duct lymph from two patients had no effects on their myasthenic symptoms. (5) It is suggested that thoracic duct lymph drainage can be combined with other forms of treatment in severe cases of myasthenia gravis.", "contents": "Drainage of thoracic duct lymph in twelve patients with myasthenia gravis. The effect of thoracic duct lymph drainage (5-34 days) in 12 patients with myasthenia gravis on muscular function has been followed for 5-43 months. Among the results obtained were: (1) During the drainage the myasthenic symptoms decreased markedly after 1-4 days and remained so during the drainage. (2) The doses of cholinesterase inhibitors had to be markedly reduced during the lymph drainage in eight patients. (3) Discontinuation of the lymph drainage increased the myasthenic symptoms within a few days. However, after a median observation time of 14 months with conventional treatment all but one of the patients had improved. (4) Retransfusion of the patients own cell-free lymph caused a worsening of the myasthenic symptoms. This effect could also be obtained following infusion of IgG preparations from the patients lymph. Three retransfusions of cell suspensions obtained from the thoracic duct lymph from two patients had no effects on their myasthenic symptoms. (5) It is suggested that thoracic duct lymph drainage can be combined with other forms of treatment in severe cases of myasthenia gravis."} {"id": "PMID:165081", "title": "The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase.", "content": "Quantitative studies of the action of theophylline and papaverine were performed in rat epididymal fat pads, both on the lipolytic effect and on the activity of phosphodiesterase, adenylate cyclase and protein kinase. Papaverine, a stronger inhibitor of phosphodiesterase than theophylline, did not produce lipolysis. The maximum lipolytic effect (glycerol release) of theophylline was much higher than that of epinephrine and nearly approached the effect exerted by dibutyryl cyclic AMP. While theophylline potentiated or was without any effect on lipolysis produced by epinephrine and dibutyryl cyclic AMP, papaverine at concentration 10- minus 3 M reduced the effect of both drugs as well as of theophylline by 90 per cent. These concentrations of papaverine also strongly inhibited the activity of adenylate cyclase. Neither papaverine nor theophylline prevented the activation of protein kinase by cyclic AMP. The data suggest that the lack of a lipolytic effect of papaverine migth be caused by a combination of its inhibitory effect on adenylate cyclase and direct inhibition of activation of triglyceride lipase.", "contents": "The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase. Quantitative studies of the action of theophylline and papaverine were performed in rat epididymal fat pads, both on the lipolytic effect and on the activity of phosphodiesterase, adenylate cyclase and protein kinase. Papaverine, a stronger inhibitor of phosphodiesterase than theophylline, did not produce lipolysis. The maximum lipolytic effect (glycerol release) of theophylline was much higher than that of epinephrine and nearly approached the effect exerted by dibutyryl cyclic AMP. While theophylline potentiated or was without any effect on lipolysis produced by epinephrine and dibutyryl cyclic AMP, papaverine at concentration 10- minus 3 M reduced the effect of both drugs as well as of theophylline by 90 per cent. These concentrations of papaverine also strongly inhibited the activity of adenylate cyclase. Neither papaverine nor theophylline prevented the activation of protein kinase by cyclic AMP. The data suggest that the lack of a lipolytic effect of papaverine migth be caused by a combination of its inhibitory effect on adenylate cyclase and direct inhibition of activation of triglyceride lipase."} {"id": "PMID:165082", "title": "Restoration of potassium-stimulated respiration of glycerol-treated muscle.", "content": "Agent that produced contracture in skeletal muscle, such as caffeine or K-depolarization, also caused an increased rate of oxygen consumption. Both of these functions are calcium dependent. In this study the respiratory response to K-depolarization and to caffeine was monitored in glycerol-treated and normal frog sartorius muscles. Although glycerol-treated muscle does not contract in response to K-depolarization, it does develop normal caffeine contractures. The respiratory response to both potassium and caffeine is greatly inhibited in glycerol-treated muscles. Pretreatment with dibutyryl cyclic AMP restored the respiratory response to normal levels in glycerol-treated muscle. Pretreatment with low levels of caffeine that had no effect on oxygen uptake markedly enhanced oxygen uptake with higher concentrations of caffeine and resulted in a normal respiratory response to K-depolarization even though there was no tension development. Caffeine had no effect on adenyl cyclase activity even at concentrations that markedly stimulated oxygen uptake. The data suggest that potassium stimulation of oxygen uptake in glycerol treated muscle is uncoupled by a defect in the formation of a cyclic nucleotide cofactor, rather than a defect in calcium influx.", "contents": "Restoration of potassium-stimulated respiration of glycerol-treated muscle. Agent that produced contracture in skeletal muscle, such as caffeine or K-depolarization, also caused an increased rate of oxygen consumption. Both of these functions are calcium dependent. In this study the respiratory response to K-depolarization and to caffeine was monitored in glycerol-treated and normal frog sartorius muscles. Although glycerol-treated muscle does not contract in response to K-depolarization, it does develop normal caffeine contractures. The respiratory response to both potassium and caffeine is greatly inhibited in glycerol-treated muscles. Pretreatment with dibutyryl cyclic AMP restored the respiratory response to normal levels in glycerol-treated muscle. Pretreatment with low levels of caffeine that had no effect on oxygen uptake markedly enhanced oxygen uptake with higher concentrations of caffeine and resulted in a normal respiratory response to K-depolarization even though there was no tension development. Caffeine had no effect on adenyl cyclase activity even at concentrations that markedly stimulated oxygen uptake. The data suggest that potassium stimulation of oxygen uptake in glycerol treated muscle is uncoupled by a defect in the formation of a cyclic nucleotide cofactor, rather than a defect in calcium influx."} {"id": "PMID:165097", "title": "Fluorocarbon emulsions and cerebral microcirculation.", "content": "Mice were exchange transfused with a fluorocarbon emulsion (FC-80). Their hemotocrits were reduced to levels of 10-15. They were examined within 1 hour of completion of normal or slightly accelerated in the majority of the mice. Acceleration may have been due to reduced \"blood\" viscosity. All mice with normal or reduced transit times displayed reversible increases in brain NADH levels when they were exposed to room air or 100% N-2 for brief periods, rather than to the atmosphere of 100%O-2 used to support life in these mice. A small group of mice with prolonged fluorescein transit tended to display NADH levels that failed to rise when O-2 was reduced in the inspired air. In this small subgroup, microcirculatory failure had apparently produced anoxia and maximal NADH levels even before the supply of inhaled O-2 was reduced. Many FC-80 mice displayed reversible decreases in brain pO-2 levels when inspired O-2 was reduced. Pentylenetetrazol activated the EEG of FC-80 mice. The EEG activity was reversibly reduced when the animals were briefly exposed to room air or N-2. These data suggest that fluorocarbon emulsions can support brain microcirculation, oxygenation, and electrical activity in vivo, a result which is consonant with the observations of others who have performed in vitro experiments, or observed long-term survival.", "contents": "Fluorocarbon emulsions and cerebral microcirculation. Mice were exchange transfused with a fluorocarbon emulsion (FC-80). Their hemotocrits were reduced to levels of 10-15. They were examined within 1 hour of completion of normal or slightly accelerated in the majority of the mice. Acceleration may have been due to reduced \"blood\" viscosity. All mice with normal or reduced transit times displayed reversible increases in brain NADH levels when they were exposed to room air or 100% N-2 for brief periods, rather than to the atmosphere of 100%O-2 used to support life in these mice. A small group of mice with prolonged fluorescein transit tended to display NADH levels that failed to rise when O-2 was reduced in the inspired air. In this small subgroup, microcirculatory failure had apparently produced anoxia and maximal NADH levels even before the supply of inhaled O-2 was reduced. Many FC-80 mice displayed reversible decreases in brain pO-2 levels when inspired O-2 was reduced. Pentylenetetrazol activated the EEG of FC-80 mice. The EEG activity was reversibly reduced when the animals were briefly exposed to room air or N-2. These data suggest that fluorocarbon emulsions can support brain microcirculation, oxygenation, and electrical activity in vivo, a result which is consonant with the observations of others who have performed in vitro experiments, or observed long-term survival."} {"id": "PMID:165099", "title": "[Evoked activity of cat association cortex neurons in different sleep stages].", "content": "Evoked activity of neurons in the parietal associative cortex in response to adequate and electric stimulations of the thalamic radiation fibers was studied during different phases of sleep. The number of responding neurons decreased during slow--wave and, particularly, during paradoxical sleep. With transition from phase to phase, responsiveness changed mainly in polysensory neurons which gave variable responses with long latencies. Mechanisms of change of responsiveness during the two phases appear to be different. Reliable increase of the inhibitory pause in responses during slow-wave sleep and its decrease during paradoxical sleep may indicate a strengthening of mechanisms of reciprocal inhibition during the first phase, and their weakening during the second phase.", "contents": "[Evoked activity of cat association cortex neurons in different sleep stages]. Evoked activity of neurons in the parietal associative cortex in response to adequate and electric stimulations of the thalamic radiation fibers was studied during different phases of sleep. The number of responding neurons decreased during slow--wave and, particularly, during paradoxical sleep. With transition from phase to phase, responsiveness changed mainly in polysensory neurons which gave variable responses with long latencies. Mechanisms of change of responsiveness during the two phases appear to be different. Reliable increase of the inhibitory pause in responses during slow-wave sleep and its decrease during paradoxical sleep may indicate a strengthening of mechanisms of reciprocal inhibition during the first phase, and their weakening during the second phase."} {"id": "PMID:165113", "title": "Phosphorylation of purified thyroid plasma membranes incubated with [32-P]ATP.", "content": "Plasma membranes have been prepared from porcine thyroid glands using sucrose gradients. The fractions having a density in sucrose of 1.18 g/ml mainly contained plasma membranes and were moderately contaminated with other subcellular components as shown by marker enzyme data. Purified plasma membranes incubated in the presence of [32-P]gamma ATP incorporated 32-P. Kinetics of incorporation of 32-P into endogenous substrates studied in various buffers and with increasing ATP concentration suggest a phosphodephosphorylating system related to cAMP-dependent protein kinase and phosphoprotein phosphatase activities. The two enzymatic activities associated with plasma membranes have been demonstrated using exogenous substrates. cAMP increases and fluoride ions decrease the extent of membrane phosphorylation. The specific activity of protein kinase was 10-12 times higher than in the initial homogenate and was only slightly enhanced in the presence of 0.5% Nonidet as compared to microsomal fraction. cAMP binding to membrane proteins was 3 times higher than to the other particulate fractions. TSH present in the incubating medium or added after 5 min of 32-P labelling induced a rapid stimulation of endogenous phosphorylation followed by a rapid decrease. Phosphorylated membrane substrates were analyzed: high voltage paper electrophoresis after partial hydrolysis indicated that [32-P]phosphate is incorporated into serine and threonine residues as o-phosphate derivatives. SDS-polyacrylamide gel electrophoresis showed several 32--labelled fractions. When enhanced by cAMP, no specific phosphorylation of protein components was observed.", "contents": "Phosphorylation of purified thyroid plasma membranes incubated with [32-P]ATP. Plasma membranes have been prepared from porcine thyroid glands using sucrose gradients. The fractions having a density in sucrose of 1.18 g/ml mainly contained plasma membranes and were moderately contaminated with other subcellular components as shown by marker enzyme data. Purified plasma membranes incubated in the presence of [32-P]gamma ATP incorporated 32-P. Kinetics of incorporation of 32-P into endogenous substrates studied in various buffers and with increasing ATP concentration suggest a phosphodephosphorylating system related to cAMP-dependent protein kinase and phosphoprotein phosphatase activities. The two enzymatic activities associated with plasma membranes have been demonstrated using exogenous substrates. cAMP increases and fluoride ions decrease the extent of membrane phosphorylation. The specific activity of protein kinase was 10-12 times higher than in the initial homogenate and was only slightly enhanced in the presence of 0.5% Nonidet as compared to microsomal fraction. cAMP binding to membrane proteins was 3 times higher than to the other particulate fractions. TSH present in the incubating medium or added after 5 min of 32-P labelling induced a rapid stimulation of endogenous phosphorylation followed by a rapid decrease. Phosphorylated membrane substrates were analyzed: high voltage paper electrophoresis after partial hydrolysis indicated that [32-P]phosphate is incorporated into serine and threonine residues as o-phosphate derivatives. SDS-polyacrylamide gel electrophoresis showed several 32--labelled fractions. When enhanced by cAMP, no specific phosphorylation of protein components was observed."} {"id": "PMID:165114", "title": "Circulating antibodies and respiratory virus infections.", "content": "Most respiratory viruses infect only the respiratory mucosa and mainly the surface epithelium, and it is therefore plausible that antibody within the circulation is unable to influence them, either by preventing infection or by terminating it once it has started. However there is experimental and observational evidence that some infections are prevented by circulating antibody. This may be because circulating immunoglobulins are released onto the surface possibly because of virus cytopathic effects or hypersensitivity to a viral antigen.", "contents": "Circulating antibodies and respiratory virus infections. Most respiratory viruses infect only the respiratory mucosa and mainly the surface epithelium, and it is therefore plausible that antibody within the circulation is unable to influence them, either by preventing infection or by terminating it once it has started. However there is experimental and observational evidence that some infections are prevented by circulating antibody. This may be because circulating immunoglobulins are released onto the surface possibly because of virus cytopathic effects or hypersensitivity to a viral antigen."} {"id": "PMID:165115", "title": "Meaning of circulating antibody titers in the infections of parainfluenza 3 virus and RS virus.", "content": "It is generally accepted that secretory antibodies play a very important role in the prevention of respiratory infections, but it is also considered that the circulating antibody level is a very significant indication of the establishment of infections. In parainfluenza 3 and RS virus infections, reinfections are very common but seem to depend more or less upon circulating antibody levels. There is a correlation between circulating antibody level and infection rate in parainfluenza 3 infection in some groups of school children in our observations of about one year. In the case of RS virus infection, observations were made in some nursery institutions and an experience in school children, in which also a circulating antibody level of some degree presents indications of infection rates.", "contents": "Meaning of circulating antibody titers in the infections of parainfluenza 3 virus and RS virus. It is generally accepted that secretory antibodies play a very important role in the prevention of respiratory infections, but it is also considered that the circulating antibody level is a very significant indication of the establishment of infections. In parainfluenza 3 and RS virus infections, reinfections are very common but seem to depend more or less upon circulating antibody levels. There is a correlation between circulating antibody level and infection rate in parainfluenza 3 infection in some groups of school children in our observations of about one year. In the case of RS virus infection, observations were made in some nursery institutions and an experience in school children, in which also a circulating antibody level of some degree presents indications of infection rates."} {"id": "PMID:165116", "title": "Contribution to the study of the parainfluenza antigens.", "content": "From epidemiological data it appeared that an epidemic of parainfluenza type 1 occurred in Lyons in October-November 1967. Thereafter a few sporadic cases were detected. Then in 1970 strains were isolated which showed a change in the hemagglutinin antigen. The persistence of antibodies in the population is shorter than that of the other parainfluenza viruses (i. e. parainfluenza 3); it is not known if reinfections with parainfluenza 1 occur since there are cross-reactions by CF test between parainfluenza 1 and parainfluenza 3 which are known to cause reinfections. The study of antigens of parainfluenza strains was made by HI, Nt, CF and immunodiffusion tests with various antisera prepared in various animal species. This study showed antigenic differences and similarities between parainfluenza 1 and parainfluenza 3.", "contents": "Contribution to the study of the parainfluenza antigens. From epidemiological data it appeared that an epidemic of parainfluenza type 1 occurred in Lyons in October-November 1967. Thereafter a few sporadic cases were detected. Then in 1970 strains were isolated which showed a change in the hemagglutinin antigen. The persistence of antibodies in the population is shorter than that of the other parainfluenza viruses (i. e. parainfluenza 3); it is not known if reinfections with parainfluenza 1 occur since there are cross-reactions by CF test between parainfluenza 1 and parainfluenza 3 which are known to cause reinfections. The study of antigens of parainfluenza strains was made by HI, Nt, CF and immunodiffusion tests with various antisera prepared in various animal species. This study showed antigenic differences and similarities between parainfluenza 1 and parainfluenza 3."} {"id": "PMID:165117", "title": "The anamnestic response of the secretory immune system: A review.", "content": "Following topical immunization of the respiratory mucosa in man, persistence of antibody in the respiratory secretions can be demonstrated in some individuals for more than one year. The secretory response to replicating agents is generally more prolonged than the response to less persistent antigens. Repeat topical antigenic stimulation provokes a response which differs very little from the primary response in magnitude, duration or latency. Nevertheless, if more than 1 year following adequate primary intranasal immunization, at a time when secretory antibodies are no longer detectable, men are again vaccinated intranasally with a dose of formalin-inactivated rhinovirus vaccine which will not provoke a primary secretory immune response, some vaccinees will produce nasal antibody. Similarly in mice, a second topical immunization of the respiratory tract with a dose of tetanus toxoid which does not produce a detectable primary secretory immune response will cause 11S IgA antibodies to appear in bronchial and nasal washings. Thus, it is possible that the secretory immune system may possess certain attributes of immunologic memory as classifically defined by the responses of the internal immune system to repeated antigenic stimulation.", "contents": "The anamnestic response of the secretory immune system: A review. Following topical immunization of the respiratory mucosa in man, persistence of antibody in the respiratory secretions can be demonstrated in some individuals for more than one year. The secretory response to replicating agents is generally more prolonged than the response to less persistent antigens. Repeat topical antigenic stimulation provokes a response which differs very little from the primary response in magnitude, duration or latency. Nevertheless, if more than 1 year following adequate primary intranasal immunization, at a time when secretory antibodies are no longer detectable, men are again vaccinated intranasally with a dose of formalin-inactivated rhinovirus vaccine which will not provoke a primary secretory immune response, some vaccinees will produce nasal antibody. Similarly in mice, a second topical immunization of the respiratory tract with a dose of tetanus toxoid which does not produce a detectable primary secretory immune response will cause 11S IgA antibodies to appear in bronchial and nasal washings. Thus, it is possible that the secretory immune system may possess certain attributes of immunologic memory as classifically defined by the responses of the internal immune system to repeated antigenic stimulation."} {"id": "PMID:165118", "title": "Adenoviruses of man and animals.", "content": "Adenoviruses are capable of causing natural infections in a wide variety of vertebrates, including amphibia, birds and mammals. Although frequently causing inapparent infections, they may be associated with diseases of varying severity and localizations. The clinico-pathological manifestations most commonly associated with adenovirus infections involve the respiratory tract and the ocular conjunctiva. Involvement of the digestive, renal and nervous systems may also be observed. A state of latency with persistence of infection for prolonged periods has been described in many hosts. Many adenovirus types are oncogemic under experimental conditions but none have been associated with naturally occurring tumours. Although the diseases caused by adenoviruses tend to be mild, this is not invariably the case and these viruses may give rise to serious epidemiological situations and represent a threat to life under certain circumstances in which the use of prophylactic vaccination may be indicated.", "contents": "Adenoviruses of man and animals. Adenoviruses are capable of causing natural infections in a wide variety of vertebrates, including amphibia, birds and mammals. Although frequently causing inapparent infections, they may be associated with diseases of varying severity and localizations. The clinico-pathological manifestations most commonly associated with adenovirus infections involve the respiratory tract and the ocular conjunctiva. Involvement of the digestive, renal and nervous systems may also be observed. A state of latency with persistence of infection for prolonged periods has been described in many hosts. Many adenovirus types are oncogemic under experimental conditions but none have been associated with naturally occurring tumours. Although the diseases caused by adenoviruses tend to be mild, this is not invariably the case and these viruses may give rise to serious epidemiological situations and represent a threat to life under certain circumstances in which the use of prophylactic vaccination may be indicated."} {"id": "PMID:165119", "title": "Potential of attenuated respiratory syncytial virus vaccine for infants and children.", "content": "Respiratory syncytial virus (RSV) disease is a major cause of death and hospitalization in infancy and a frequent cause of morbidity throughout childhood. Serum antibody does not protect as is evident from the study of natural disease and use of killed vaccines. Local antibody responses occur in natural illness. Possibly serum antibody in the absence of local antibody plays a part in illness. We have studied local and serum antibody response to potential attenuated vaccines: a 26 degrees C adapted RSV and a ts mutant RSV. Both produced the desired infection as evidenced by virus recovery, serum and local antibody response. However, both appear to have had residual pathogenicity for young infants. This included mild bronchitis after the 26 degrees C RSV and mild rhinitis, which might be acceptable, but also fever and otitis in one infant after the ts RSV. Also, some of the virus recovered in the ts studies had wild type characteristics. An acceptable RSV vaccine strain will (a) infect without undergoing reversion or other genetic changes, (b) induce resistance to wild type virus, (c) cause no or very mild inflammatory changes such as the rhinitis associated with the vaccines thus far tried.", "contents": "Potential of attenuated respiratory syncytial virus vaccine for infants and children. Respiratory syncytial virus (RSV) disease is a major cause of death and hospitalization in infancy and a frequent cause of morbidity throughout childhood. Serum antibody does not protect as is evident from the study of natural disease and use of killed vaccines. Local antibody responses occur in natural illness. Possibly serum antibody in the absence of local antibody plays a part in illness. We have studied local and serum antibody response to potential attenuated vaccines: a 26 degrees C adapted RSV and a ts mutant RSV. Both produced the desired infection as evidenced by virus recovery, serum and local antibody response. However, both appear to have had residual pathogenicity for young infants. This included mild bronchitis after the 26 degrees C RSV and mild rhinitis, which might be acceptable, but also fever and otitis in one infant after the ts RSV. Also, some of the virus recovered in the ts studies had wild type characteristics. An acceptable RSV vaccine strain will (a) infect without undergoing reversion or other genetic changes, (b) induce resistance to wild type virus, (c) cause no or very mild inflammatory changes such as the rhinitis associated with the vaccines thus far tried."} {"id": "PMID:165120", "title": "Antigenic relationships of common rhinovirus types from disabling upper respiratory illnesses.", "content": "The frequency of the common cold has been though to be due to the existence of more than 89 different serologic types of rhinoviruses. However, in the civilian and military population studied in this area from 1962 through 1970, types 1A, 1B, 2, 23, 29, 30 and 31 accounted for 81 percent of 487 rhinoviruses isolated from individuals with respiratory illnesses. Antigenic relationships between these types and others have been demonstrated by neutralization in WI-38 cell cultures and by immunodiffusion. Types 1A and 1b, 2 and 49, 23 and 30, 29 and 44 and others are related. With specific animal antisera, heterotypic antibody titers are minimal. However, following natural infection in man with one of these related types, antibody responses to the other was almost equal to the homotype and could predictably provide cross-protection. Even with inactive T13 rhinovirus vaccine in man, protective levels of neutralizing antibody to T41 were produced. It is clear that the rates of rhinovirus colds would be greatly increased if more than 89 immunologic distinct types actually existed. An effective vaccine could be easily prepared by selection of a few appropriate types, such as 1A, 2, 23, 29 and 31.", "contents": "Antigenic relationships of common rhinovirus types from disabling upper respiratory illnesses. The frequency of the common cold has been though to be due to the existence of more than 89 different serologic types of rhinoviruses. However, in the civilian and military population studied in this area from 1962 through 1970, types 1A, 1B, 2, 23, 29, 30 and 31 accounted for 81 percent of 487 rhinoviruses isolated from individuals with respiratory illnesses. Antigenic relationships between these types and others have been demonstrated by neutralization in WI-38 cell cultures and by immunodiffusion. Types 1A and 1b, 2 and 49, 23 and 30, 29 and 44 and others are related. With specific animal antisera, heterotypic antibody titers are minimal. However, following natural infection in man with one of these related types, antibody responses to the other was almost equal to the homotype and could predictably provide cross-protection. Even with inactive T13 rhinovirus vaccine in man, protective levels of neutralizing antibody to T41 were produced. It is clear that the rates of rhinovirus colds would be greatly increased if more than 89 immunologic distinct types actually existed. An effective vaccine could be easily prepared by selection of a few appropriate types, such as 1A, 2, 23, 29 and 31."} {"id": "PMID:165121", "title": "An animal model for studying infection and immunity to and attenuation of human parainfluenza viruses.", "content": "Neonatal ferrets were found to be highly via the intranasal route of inoculation to infection with wild type isolates of parainfluenza viruses. Wild type infection consistently resulted in deaths of these animals in 48 to 72 hours. Autopsy and histopathological findings in lung tissue were consistent with those of viral infection. Virus could consistently be isolated from lung tissues. Using wild green monkey kidney grown viruses and selected passage levels of egg adapted viruses, virus attenuation markers were observed by comparing infectivity in neonatal ferrets, propagation in cell cultures of human, primate, rabbit and chick embryo tissues, and in chick embryos and interferon induction. Adult pregant dams could be immunized (silently infected) and circulating hemagglutinin-inhibiting antibody could be detected within two weeks of intranasal instillation of wild and low egg passage types of virus. The animal model described could be valuable in studying immunity to parainfluenza virus infections.", "contents": "An animal model for studying infection and immunity to and attenuation of human parainfluenza viruses. Neonatal ferrets were found to be highly via the intranasal route of inoculation to infection with wild type isolates of parainfluenza viruses. Wild type infection consistently resulted in deaths of these animals in 48 to 72 hours. Autopsy and histopathological findings in lung tissue were consistent with those of viral infection. Virus could consistently be isolated from lung tissues. Using wild green monkey kidney grown viruses and selected passage levels of egg adapted viruses, virus attenuation markers were observed by comparing infectivity in neonatal ferrets, propagation in cell cultures of human, primate, rabbit and chick embryo tissues, and in chick embryos and interferon induction. Adult pregant dams could be immunized (silently infected) and circulating hemagglutinin-inhibiting antibody could be detected within two weeks of intranasal instillation of wild and low egg passage types of virus. The animal model described could be valuable in studying immunity to parainfluenza virus infections."} {"id": "PMID:165122", "title": "Etiological relationship between several respiratory viruses and acute respiratory diseases in 1973 in the GDR.", "content": "The role of some important respiratory viruses (influenza A, B, parainfluenza, adeno and mycoplasma) in morbidity due to acute respiratory diseases during 1973 in the GDR is analysed on account of serological data (CFR) obtained with paired sera (a -5 percent of all cases comprising all age groups) and virus isolations. The serological surveillance provides an important base for evaluating the significance of respiratory agents for the development of the morbidity due to ARD.", "contents": "Etiological relationship between several respiratory viruses and acute respiratory diseases in 1973 in the GDR. The role of some important respiratory viruses (influenza A, B, parainfluenza, adeno and mycoplasma) in morbidity due to acute respiratory diseases during 1973 in the GDR is analysed on account of serological data (CFR) obtained with paired sera (a -5 percent of all cases comprising all age groups) and virus isolations. The serological surveillance provides an important base for evaluating the significance of respiratory agents for the development of the morbidity due to ARD."} {"id": "PMID:165123", "title": "A case of pneumonia associated with cytomegalovirus (CMV) and anti- CMV antibody detection.", "content": "A case of pneumonia associated with acute CMV infection is reported. A 34 year-old man was admitted with fever (39 degrees C equals 102.2 degrees F), malaise and dyspnea. Clinical findings were characteristic of viral pneumonia. Crepitant rales to chest auscultation were heard all over the lung. X-ray picture showed evidence of interstitial pneumonia. Leucocyte counts were normal whilst lymphocyte counts elevated. Bone marrow examination showed an increase of lymphocytes and lymphoblasts. To palpation liver and spleen were slightly enlarged. Liver function tests were slightly abnormal. Bacteriological tests on urine and blood and Paul-Bunnel test were negative. Antibiotic therapy was ineffective. CMV was isolated from saliva and urine. Serological studies (elevated CF and precipitin antibody titer) suggested the diagnosis of a CMV infection. The patient recovered in 3 weeks.", "contents": "A case of pneumonia associated with cytomegalovirus (CMV) and anti- CMV antibody detection. A case of pneumonia associated with acute CMV infection is reported. A 34 year-old man was admitted with fever (39 degrees C equals 102.2 degrees F), malaise and dyspnea. Clinical findings were characteristic of viral pneumonia. Crepitant rales to chest auscultation were heard all over the lung. X-ray picture showed evidence of interstitial pneumonia. Leucocyte counts were normal whilst lymphocyte counts elevated. Bone marrow examination showed an increase of lymphocytes and lymphoblasts. To palpation liver and spleen were slightly enlarged. Liver function tests were slightly abnormal. Bacteriological tests on urine and blood and Paul-Bunnel test were negative. Antibiotic therapy was ineffective. CMV was isolated from saliva and urine. Serological studies (elevated CF and precipitin antibody titer) suggested the diagnosis of a CMV infection. The patient recovered in 3 weeks."} {"id": "PMID:165124", "title": "Immune response of cattle to intranasally or parenterally administered parainfluenza type 3 virus vaccines.", "content": "The principal significance of PI-3 virus in the bovine respiratory disease complex would seem to be its role in predisposing the respiratory tract to bacterial infection by (5) disrupting the integrity of the superficial mucosa and (3) producing a more favourable milieu for bacterial growth. Attention has therefore been given to establishing local immunity to preclude infection of superficial cells of the mucosa. Criteria used to evaluate the degree of such immunity are (5) presence of specific antibody activity in nasal secretions and (3) extent of virus excretion in nasal secretions following challenge with low passage virus. Studies completed thus far demonstrate that modified, live PI-3 virus administered intranasally is more effective than either modified, live or inactivated PI-3 virusadministered by parenteral injection in providing antibody activity in respiratory tractsecretions and in reducing virus excretion following challenge. IgA antibodies, presumably synthesized locally, apparently contribute heavily to the total antibody activity present in respiratory tract secretions.", "contents": "Immune response of cattle to intranasally or parenterally administered parainfluenza type 3 virus vaccines. The principal significance of PI-3 virus in the bovine respiratory disease complex would seem to be its role in predisposing the respiratory tract to bacterial infection by (5) disrupting the integrity of the superficial mucosa and (3) producing a more favourable milieu for bacterial growth. Attention has therefore been given to establishing local immunity to preclude infection of superficial cells of the mucosa. Criteria used to evaluate the degree of such immunity are (5) presence of specific antibody activity in nasal secretions and (3) extent of virus excretion in nasal secretions following challenge with low passage virus. Studies completed thus far demonstrate that modified, live PI-3 virus administered intranasally is more effective than either modified, live or inactivated PI-3 virusadministered by parenteral injection in providing antibody activity in respiratory tractsecretions and in reducing virus excretion following challenge. IgA antibodies, presumably synthesized locally, apparently contribute heavily to the total antibody activity present in respiratory tract secretions."} {"id": "PMID:165125", "title": "Vaccination against parainfluenza 1 virus (typus muris) infection in order to eradicate this virus in colonies of laboratory animals.", "content": "Parainfluenza 1 virus (typus muris), commonly known as Sendai virus, is still contaminating mouse colonies in Japan. This presents a serious problem to keep mouse colonies pathogen-free. It seems that the infection is spread by dust and the virus remains active a considerable time in the mouse breeding rooms after all mice are removed. In order to eradicate the infection of this virus, vaccination was attempted to inoculate newly born young mice successively for about six months and during and after these periods the movements of the infection were under observation. The vaccine used for this experiment was inactivated virus vaccine with mineral oil-Arlacel adjuvant. The induction of antibody level by the inoculation of this vaccine was evidenced to be very efficient and the duration of the immunity was also very satisfactory. However, after the cessation of the vaccination, the infection of the virus reappeared gradually after some period of temporary ease.", "contents": "Vaccination against parainfluenza 1 virus (typus muris) infection in order to eradicate this virus in colonies of laboratory animals. Parainfluenza 1 virus (typus muris), commonly known as Sendai virus, is still contaminating mouse colonies in Japan. This presents a serious problem to keep mouse colonies pathogen-free. It seems that the infection is spread by dust and the virus remains active a considerable time in the mouse breeding rooms after all mice are removed. In order to eradicate the infection of this virus, vaccination was attempted to inoculate newly born young mice successively for about six months and during and after these periods the movements of the infection were under observation. The vaccine used for this experiment was inactivated virus vaccine with mineral oil-Arlacel adjuvant. The induction of antibody level by the inoculation of this vaccine was evidenced to be very efficient and the duration of the immunity was also very satisfactory. However, after the cessation of the vaccination, the infection of the virus reappeared gradually after some period of temporary ease."} {"id": "PMID:165126", "title": "Local and systemic response after simultaneous intranasal inoculation of temperature-sensitive mutants of parainfluenza 3, IBR and bovine adenovirus 3.", "content": "Triple seronegative calves were exposed by the nasal route to three (ts) mutants of bovine respiratory viruses (PI3, IBR, Adeno3). After a single exposure, they responded with significant levels of serum antibodies to the three viruses. Nasal antibodies were demonstrated for PI3 and adenovirus antigens. The failure to demonstrate nasal antibodies to IBR may be due to lack of sensitivity of the procedure used. When reexposed six weeks later, calves had sharp increases in levels of serum antibodies and developed a secondary type response at the local level for all three viruses. The persistence of the local antibodies was much longer after reexposure than after primary inoculation. This study indicates that the simultaneous application of these three (ts) viruses by the respiratory route is perfectly safe and affords a long lasting immunity towards homologous respiratory infections.", "contents": "Local and systemic response after simultaneous intranasal inoculation of temperature-sensitive mutants of parainfluenza 3, IBR and bovine adenovirus 3. Triple seronegative calves were exposed by the nasal route to three (ts) mutants of bovine respiratory viruses (PI3, IBR, Adeno3). After a single exposure, they responded with significant levels of serum antibodies to the three viruses. Nasal antibodies were demonstrated for PI3 and adenovirus antigens. The failure to demonstrate nasal antibodies to IBR may be due to lack of sensitivity of the procedure used. When reexposed six weeks later, calves had sharp increases in levels of serum antibodies and developed a secondary type response at the local level for all three viruses. The persistence of the local antibodies was much longer after reexposure than after primary inoculation. This study indicates that the simultaneous application of these three (ts) viruses by the respiratory route is perfectly safe and affords a long lasting immunity towards homologous respiratory infections."} {"id": "PMID:165127", "title": "Antibody levels and immunity to infectious bovine rhinotracheitis virus (IBR) infections in Wisconsin dairy cattle.", "content": "Individual cows and calves in 7 Holstein-Friesian herds with a history of respiratory disease in Green County, Wisconsin, USA, were swabbed intranasally and bled monthly, some for periods over 1 year. Virus isolation and serological procedures were completed on the samples in an attempt to recognize the problems and peculiarities that IBR virus continues to cause in dairy cows, in spite of, and possibly because of vaccines available for immunization against this agent. While IBR virus was isolated from animals on 6/7 farms over the period of study the history of vaccination with Nasalgen IP prevented the differentiation of vaccine (avirulent) virus from field (virulent) virus. IBR virus was isolated from apparently healthy animals as well as animals having signs of respiratory disease. IBR virus was assumed to be the cause of recurrent respiratory disease and ocular disease on at least two of the farms studied as established by virus isolation, serology, and the presence of characteristic signs of respiratory disease. While IBR virus was present on the other five farms its precise role in the diseases observed was not determined. IBR virus, whether vaccine virus or field virus, appeared to be persistent in 6/7 of the herds studied. Keratoconjunctivitis and corneal ulceration were the only signs of disease in animals in one herd where the etiologic agent was presumed to be field strain IBR virus. Antibody to IBR virus did not protect animals from respiratory or ocular disease in which IBR virus was thought to be a causative agent. Adult animals that had antibody to IBR virus at the time of vaccination with Nasalgen IP generally did not respond after vaccination with an increase in IBR virus antibody. Those adults that did not have antibody prior to vaccination, generally responded to vaccination with a rise in antibody. Vaccination of calves with Nasalgen IP generally did not cause an increase in antibody. IBR virus antibody was higher in vaccinated herds with recurrent respiratory disease.", "contents": "Antibody levels and immunity to infectious bovine rhinotracheitis virus (IBR) infections in Wisconsin dairy cattle. Individual cows and calves in 7 Holstein-Friesian herds with a history of respiratory disease in Green County, Wisconsin, USA, were swabbed intranasally and bled monthly, some for periods over 1 year. Virus isolation and serological procedures were completed on the samples in an attempt to recognize the problems and peculiarities that IBR virus continues to cause in dairy cows, in spite of, and possibly because of vaccines available for immunization against this agent. While IBR virus was isolated from animals on 6/7 farms over the period of study the history of vaccination with Nasalgen IP prevented the differentiation of vaccine (avirulent) virus from field (virulent) virus. IBR virus was isolated from apparently healthy animals as well as animals having signs of respiratory disease. IBR virus was assumed to be the cause of recurrent respiratory disease and ocular disease on at least two of the farms studied as established by virus isolation, serology, and the presence of characteristic signs of respiratory disease. While IBR virus was present on the other five farms its precise role in the diseases observed was not determined. IBR virus, whether vaccine virus or field virus, appeared to be persistent in 6/7 of the herds studied. Keratoconjunctivitis and corneal ulceration were the only signs of disease in animals in one herd where the etiologic agent was presumed to be field strain IBR virus. Antibody to IBR virus did not protect animals from respiratory or ocular disease in which IBR virus was thought to be a causative agent. Adult animals that had antibody to IBR virus at the time of vaccination with Nasalgen IP generally did not respond after vaccination with an increase in IBR virus antibody. Those adults that did not have antibody prior to vaccination, generally responded to vaccination with a rise in antibody. Vaccination of calves with Nasalgen IP generally did not cause an increase in antibody. IBR virus antibody was higher in vaccinated herds with recurrent respiratory disease."} {"id": "PMID:165128", "title": "Immune response to infectious bovine rhinotracheitis virus (IBRV) following natural infection or vaccination by intranasally or parenterally administered vaccines.", "content": "Neutralizing antibody activity is present in serum and nasal secretions of cattle following IBR virulent virus challenge or intranasal vaccination with live, avirulent virus. Levels of nasal secretion antibody activity (NS-AA) are low and short-lived following initial exposure, but are considerably enhanced following reexposure provided infection occurs. NS-AA has not been detected in calves following parenteral administration of live virus vaccine. Such calves are subject to infection by challenge virus administered intranasally as early as three weeks after vaccination. Unlike parenterally administered vaccine, vaccine administeredintranasally promotes active immunity in young calves born of immune dams. Calves so vaccinated respond to later challenge with rapid, pronounced increases in both serum antibody and NS-AA without displaying overt signs of disease. Avirulent virus administered intranasally promotes release of interferon into nasal secretions for a period of six to eight days, coincident with continued virus replication. Classes of immunoglobulin involved in the various responses will be discussed.", "contents": "Immune response to infectious bovine rhinotracheitis virus (IBRV) following natural infection or vaccination by intranasally or parenterally administered vaccines. Neutralizing antibody activity is present in serum and nasal secretions of cattle following IBR virulent virus challenge or intranasal vaccination with live, avirulent virus. Levels of nasal secretion antibody activity (NS-AA) are low and short-lived following initial exposure, but are considerably enhanced following reexposure provided infection occurs. NS-AA has not been detected in calves following parenteral administration of live virus vaccine. Such calves are subject to infection by challenge virus administered intranasally as early as three weeks after vaccination. Unlike parenterally administered vaccine, vaccine administeredintranasally promotes active immunity in young calves born of immune dams. Calves so vaccinated respond to later challenge with rapid, pronounced increases in both serum antibody and NS-AA without displaying overt signs of disease. Avirulent virus administered intranasally promotes release of interferon into nasal secretions for a period of six to eight days, coincident with continued virus replication. Classes of immunoglobulin involved in the various responses will be discussed."} {"id": "PMID:165129", "title": "Infectious bovine rhinotracheitis virus. History and recent developments.", "content": "The infectious bovine rhinotracheitis (IBR) virus belongs to the group of herpes viruses. It causes in cattle a severe disease predominantly in the upper respiratory tract. Morbidity rate is 100 percent, mortality - depending on hygienic and other factors - ranges from 0-15 percent. The IBR virus is serologically indistinguishable from the infect pustulat vulvovaginitis (IPV) virus which causes disorders of the genital tract in both male and female cattle. Possibly the IPV virus is the older of the two. Already in the twenties it had been isolated and described in Europe whereas IBR virus was first isolated from feedlot cattle in the USA during 1955/1956. Most likely - experiments also gave a hint - the IPV virus increased its virulence for the respiratory tract by rapid and numerous passages as this was only possible in accumulations of tremendous heads of animals. Vaccines both live attenuated and killed ones have been developed. Killed ones are always administered parenterally; the live ones are either intramuscularly injected or locally sprayed (into the nasal cavity). Immunity is developed within 3 weeks, however, if vaccinated animals are challenged, virus is again shed for a number of days. Cattle thereby do not exhibit any symptoms of disease. This is true following any kind of vaccination (live or killed). After local administration of live vaccines, however, the production of interferon by the cells of the respiratory tract is remarkable whereas parenterally administration of vaccine does not lead to that.", "contents": "Infectious bovine rhinotracheitis virus. History and recent developments. The infectious bovine rhinotracheitis (IBR) virus belongs to the group of herpes viruses. It causes in cattle a severe disease predominantly in the upper respiratory tract. Morbidity rate is 100 percent, mortality - depending on hygienic and other factors - ranges from 0-15 percent. The IBR virus is serologically indistinguishable from the infect pustulat vulvovaginitis (IPV) virus which causes disorders of the genital tract in both male and female cattle. Possibly the IPV virus is the older of the two. Already in the twenties it had been isolated and described in Europe whereas IBR virus was first isolated from feedlot cattle in the USA during 1955/1956. Most likely - experiments also gave a hint - the IPV virus increased its virulence for the respiratory tract by rapid and numerous passages as this was only possible in accumulations of tremendous heads of animals. Vaccines both live attenuated and killed ones have been developed. Killed ones are always administered parenterally; the live ones are either intramuscularly injected or locally sprayed (into the nasal cavity). Immunity is developed within 3 weeks, however, if vaccinated animals are challenged, virus is again shed for a number of days. Cattle thereby do not exhibit any symptoms of disease. This is true following any kind of vaccination (live or killed). After local administration of live vaccines, however, the production of interferon by the cells of the respiratory tract is remarkable whereas parenterally administration of vaccine does not lead to that."} {"id": "PMID:165130", "title": "Live and killed virus vaccines: their use against the respiratory diseases of cattle.", "content": "The respiratory diseases of cattle are due to a combination of different factors among which figures a viral infection. The antiviral vaccination, perfectly possible owing to associated killed vaccines and live virus, is thus a very important element which must enter into every general plan of prophylaxis. Moreover, these plans will concern bacterial infections, conditions of rearing, etc. We have demonstrated that it is possible to produce good immunity in calves and sheep using a trivalent killed vaccine (parainfluenza 3, adenovirus 3 and reovirus 1). Possible interference with antibodies of maternal origin makes the multiplication of vaccine injections desirable.", "contents": "Live and killed virus vaccines: their use against the respiratory diseases of cattle. The respiratory diseases of cattle are due to a combination of different factors among which figures a viral infection. The antiviral vaccination, perfectly possible owing to associated killed vaccines and live virus, is thus a very important element which must enter into every general plan of prophylaxis. Moreover, these plans will concern bacterial infections, conditions of rearing, etc. We have demonstrated that it is possible to produce good immunity in calves and sheep using a trivalent killed vaccine (parainfluenza 3, adenovirus 3 and reovirus 1). Possible interference with antibodies of maternal origin makes the multiplication of vaccine injections desirable."} {"id": "PMID:165131", "title": "Studies on immunity to Aujeszky's disease (pseudorabies) virus infection in pigs.", "content": "Aujeszky's disease is primarily a disease of pigs caused by a herpesvirus. In pigs, the primary site of virus replication is the nasopharynx. Some strains cause lesions only in the central nervous system, others cause rhinitis, pneumonia and encephalitis. Colostrum from immune sows protected 3 day old piglets from experimental infection, but did not prevent the piglets excreting virus. Colostral antibodies were 11-16-fold greater than the serum titres in the sows and the half life of passiveantibody was 8.5 days. Pigs given virus vaccine intramuscularly did not excret vaccine virus whereas live vaccine virus given intranasally was excreted. Although only low titres of serum neutralizing antibody were detected, vaccination gave good protection against severe experimental challenge; the intranasally vaccinated group was better protected. A naturally occurring local strain and temperature-sensitive mutants are being examined as potential vaccines.", "contents": "Studies on immunity to Aujeszky's disease (pseudorabies) virus infection in pigs. Aujeszky's disease is primarily a disease of pigs caused by a herpesvirus. In pigs, the primary site of virus replication is the nasopharynx. Some strains cause lesions only in the central nervous system, others cause rhinitis, pneumonia and encephalitis. Colostrum from immune sows protected 3 day old piglets from experimental infection, but did not prevent the piglets excreting virus. Colostral antibodies were 11-16-fold greater than the serum titres in the sows and the half life of passiveantibody was 8.5 days. Pigs given virus vaccine intramuscularly did not excret vaccine virus whereas live vaccine virus given intranasally was excreted. Although only low titres of serum neutralizing antibody were detected, vaccination gave good protection against severe experimental challenge; the intranasally vaccinated group was better protected. A naturally occurring local strain and temperature-sensitive mutants are being examined as potential vaccines."} {"id": "PMID:165132", "title": "Immunity to infections of the respiratory system in man and animals.", "content": "Itis probable that RS virus is an important etiological agent in the bovine respiratory disease syndrome. This is the conclusion of groups of workers in Europe and Japan. In this country, significant levels of neutralizing antibody have been detected in 81 percent of cattle tested, while paired sera groups showed seroconversions of between 17 and 29 percent. RS virus has also been isolated from diseased calves and such isolates produce pyrexia and rhinitis in experimentally infected calves. The virus is localised in the respiratory tract. Serum antibody responses have not been consistent but it is likely that moderate serum antibody levels indicate that the animal is protected. These antibody levels can be achieved by injection of a formalin inactivated antigen. Calves vaccinated in this way showed no definite evidence of exacerbation of disease when challenged with infectious virus.", "contents": "Immunity to infections of the respiratory system in man and animals. Itis probable that RS virus is an important etiological agent in the bovine respiratory disease syndrome. This is the conclusion of groups of workers in Europe and Japan. In this country, significant levels of neutralizing antibody have been detected in 81 percent of cattle tested, while paired sera groups showed seroconversions of between 17 and 29 percent. RS virus has also been isolated from diseased calves and such isolates produce pyrexia and rhinitis in experimentally infected calves. The virus is localised in the respiratory tract. Serum antibody responses have not been consistent but it is likely that moderate serum antibody levels indicate that the animal is protected. These antibody levels can be achieved by injection of a formalin inactivated antigen. Calves vaccinated in this way showed no definite evidence of exacerbation of disease when challenged with infectious virus."} {"id": "PMID:165133", "title": "The importance of picornavirus infections in respiratory disease of man and other mammals.", "content": "Picornaviruses may be divided, by physicochemical properties, into enteroviruses, cardioviruses, caliciviruses, rhinoviruses and foot-and-mouth diseases viruses. Although the respiratory tract may be the primary site of entry and multiplication for enteroviruses, cardioviruses and FMD viruses, few agents in these groups cause respiratory disease. A notable exception is coxsackievirus A21 which is an important cause of upper respiratory tract diseases in military recruits. The picornaviruses which most frequently cause respiratory illness are rhinoviruses and caliciviruses. There are over one hundred rhinovirus serotypes which infect man and they have been isolated from up to 50 percent of cases of mild respiratory illness, from 1-2 percent of healthy adults and from 5-10 percent of healthy children. About 10 percent of rhinovirus infections in adults are symptomless. The two bovine serotypes of rhinovirus and the two equine serotypes frequently infect cattle and horses respectively but seldom cause disease. Numerous calicivirus serotypes have been found in 17 percent of cats with respiratory disease and in 19 percent of clinically normal cats. However, experimental inoculation with caliciviruses has confirmed their causative role in respiratory disease of cats. The high rate of virus isolation from normal cats is probably due to their ability to carry virus in an infectious form for up to two years after initial infection and illness.", "contents": "The importance of picornavirus infections in respiratory disease of man and other mammals. Picornaviruses may be divided, by physicochemical properties, into enteroviruses, cardioviruses, caliciviruses, rhinoviruses and foot-and-mouth diseases viruses. Although the respiratory tract may be the primary site of entry and multiplication for enteroviruses, cardioviruses and FMD viruses, few agents in these groups cause respiratory disease. A notable exception is coxsackievirus A21 which is an important cause of upper respiratory tract diseases in military recruits. The picornaviruses which most frequently cause respiratory illness are rhinoviruses and caliciviruses. There are over one hundred rhinovirus serotypes which infect man and they have been isolated from up to 50 percent of cases of mild respiratory illness, from 1-2 percent of healthy adults and from 5-10 percent of healthy children. About 10 percent of rhinovirus infections in adults are symptomless. The two bovine serotypes of rhinovirus and the two equine serotypes frequently infect cattle and horses respectively but seldom cause disease. Numerous calicivirus serotypes have been found in 17 percent of cats with respiratory disease and in 19 percent of clinically normal cats. However, experimental inoculation with caliciviruses has confirmed their causative role in respiratory disease of cats. The high rate of virus isolation from normal cats is probably due to their ability to carry virus in an infectious form for up to two years after initial infection and illness."} {"id": "PMID:165134", "title": "Hepatic dearterialization in 3'-methyl-4-dimethylaminoazo-benzene-induced hepatocellular carcinoma with special reference to circulatory dynamics and mitochondrial functions.", "content": "This time trend of hemodynamics and mitochondrial functions were studied to determine whether the ligation of the hepatic artery would result in an antitumor effect on 3'-methyl-4-dimethylaminoazobenzene-induced hepatic carcinoma in rats. The studies revealed that the hepatic tumors were nourished predominantly by the artery and less by the portal vein; the size of the vascular beds in the hepatic tumors decreased as compared with those in the non-tumor area; and as the tumors grew larger, the artery became less predominant and the size of vascular beds decreased further. The mitochondria in the tumor were characterized by impaired growth, impaired oxidative phosphorylation, and by the low activity and nucleotide specificity of membrane bound ATPase. Hepatic dearterialization enhanced ischemia in the tumors and was accompanied by intensified impairment of the aerobic energy production, resulting in necrosis of the tumor. The effects of the dearterialization tended to decrease after the 5th day following the operation. In view of the gross findings upon relaparotomy and the recovery of hemodynamics and mitochondrial functions, this tendency appeared to be chiefly attributed to the increasing collateral circulation.", "contents": "Hepatic dearterialization in 3'-methyl-4-dimethylaminoazo-benzene-induced hepatocellular carcinoma with special reference to circulatory dynamics and mitochondrial functions. This time trend of hemodynamics and mitochondrial functions were studied to determine whether the ligation of the hepatic artery would result in an antitumor effect on 3'-methyl-4-dimethylaminoazobenzene-induced hepatic carcinoma in rats. The studies revealed that the hepatic tumors were nourished predominantly by the artery and less by the portal vein; the size of the vascular beds in the hepatic tumors decreased as compared with those in the non-tumor area; and as the tumors grew larger, the artery became less predominant and the size of vascular beds decreased further. The mitochondria in the tumor were characterized by impaired growth, impaired oxidative phosphorylation, and by the low activity and nucleotide specificity of membrane bound ATPase. Hepatic dearterialization enhanced ischemia in the tumors and was accompanied by intensified impairment of the aerobic energy production, resulting in necrosis of the tumor. The effects of the dearterialization tended to decrease after the 5th day following the operation. In view of the gross findings upon relaparotomy and the recovery of hemodynamics and mitochondrial functions, this tendency appeared to be chiefly attributed to the increasing collateral circulation."} {"id": "PMID:165135", "title": "Phytobezoar occurring as a complication of gastric carcinoma.", "content": "Phytobezoar occurring as a complication of gastric carcinoma is reported for the first time. A review of the pathogenesis of phytobezoar suggests that hypomotility and hyposecretion are the two most important factors in bezoar formation. In the case discussed, hypomotility as a consequence of neoplastic involvement of the gastric antrum was the most important precipitating factor. However, documentation of prior hyposecretion was also noted and suggests that a combination of these two factors may be more significant than each taken alone. The therapeutic management of bezoars in patients who are not candidates for surgery is frequently difficult. This is the third case in which the enzyme cellulase has been used successfully for bezoar dissolution.", "contents": "Phytobezoar occurring as a complication of gastric carcinoma. Phytobezoar occurring as a complication of gastric carcinoma is reported for the first time. A review of the pathogenesis of phytobezoar suggests that hypomotility and hyposecretion are the two most important factors in bezoar formation. In the case discussed, hypomotility as a consequence of neoplastic involvement of the gastric antrum was the most important precipitating factor. However, documentation of prior hyposecretion was also noted and suggests that a combination of these two factors may be more significant than each taken alone. The therapeutic management of bezoars in patients who are not candidates for surgery is frequently difficult. This is the third case in which the enzyme cellulase has been used successfully for bezoar dissolution."} {"id": "PMID:165136", "title": "Role of DNA sequences in genetic recombination in the iso-1-cytochrome c gene of yeast. I. Discrepancies between physical distances and genetic distances determined by five mapping procedures.", "content": "Recombination rates have been examined in two-point crosses of various defined cyc1 mutants using five mapping methods. Nucleotide sequences of mutant codons were identified in previous studies from alterations in functional iso-1-cytochromes c produced by intragenic revertants. Heteroallelic diploids were analyzed for rates of mitotic recombination that occurred spontaneously and that were induced with x-rays, ultraviolet light and the near-ultraviolet light emitted by sunlamps, as well as rates of meiotic recombination that occur after sporulation. Frequencies of both mitotic and meiotic recombination do not necessarily correspond with physical distances separating altered nucleotides. The most extreme discrepancy involved two adjacent intervals of thirteen basepairs which differed approximately thirty-fold in their spontaneous and X-ray-induced recombination rates. Marked disproportions between genetic and physical distances appear to be due to the interaction of the two nucleotide sequences in the heteroallelic combination and not to the sequences of the mutant codons alone. Recombination values that were obtained by all five methods could not be used to establish to correct order of mutant sitesmrelationships of the recombination rates for the various pairwise crosses are different after mitosis from those after meiosis, suggesting that these two recombinational processes are to some extent different in their dependence on particular nucleotide configurations. On the other hand, the relationships of the rates induced by UV-, sunlamp- and X-irradiation were identical or very similar. In addition to the intrinsic properties of the alleles affecting frequencies of mitotic and meiotic recombination rates, two- to threefold variations in recombination rates could be attributed to genetic backgrounds.", "contents": "Role of DNA sequences in genetic recombination in the iso-1-cytochrome c gene of yeast. I. Discrepancies between physical distances and genetic distances determined by five mapping procedures. Recombination rates have been examined in two-point crosses of various defined cyc1 mutants using five mapping methods. Nucleotide sequences of mutant codons were identified in previous studies from alterations in functional iso-1-cytochromes c produced by intragenic revertants. Heteroallelic diploids were analyzed for rates of mitotic recombination that occurred spontaneously and that were induced with x-rays, ultraviolet light and the near-ultraviolet light emitted by sunlamps, as well as rates of meiotic recombination that occur after sporulation. Frequencies of both mitotic and meiotic recombination do not necessarily correspond with physical distances separating altered nucleotides. The most extreme discrepancy involved two adjacent intervals of thirteen basepairs which differed approximately thirty-fold in their spontaneous and X-ray-induced recombination rates. Marked disproportions between genetic and physical distances appear to be due to the interaction of the two nucleotide sequences in the heteroallelic combination and not to the sequences of the mutant codons alone. Recombination values that were obtained by all five methods could not be used to establish to correct order of mutant sitesmrelationships of the recombination rates for the various pairwise crosses are different after mitosis from those after meiosis, suggesting that these two recombinational processes are to some extent different in their dependence on particular nucleotide configurations. On the other hand, the relationships of the rates induced by UV-, sunlamp- and X-irradiation were identical or very similar. In addition to the intrinsic properties of the alleles affecting frequencies of mitotic and meiotic recombination rates, two- to threefold variations in recombination rates could be attributed to genetic backgrounds."} {"id": "PMID:165138", "title": "[Physiopathology of the Holmes-Adie syndrome. Neurophysiological examinations of the autoreflex disorder].", "content": "Areflexia of 8 patients with Holmes-Adie-syndrome was investigated. The voluntary movements, electromyograms, motor and sensory nerve conduction velocities and the nerve action potentials were normal. The mechanically elicited afferents of mechanoreceptors of the soleus muscle (recorded with semimicro-electrodes) were not different in Holmes-Adie-patients with areflexia and normals.", "contents": "[Physiopathology of the Holmes-Adie syndrome. Neurophysiological examinations of the autoreflex disorder]. Areflexia of 8 patients with Holmes-Adie-syndrome was investigated. The voluntary movements, electromyograms, motor and sensory nerve conduction velocities and the nerve action potentials were normal. The mechanically elicited afferents of mechanoreceptors of the soleus muscle (recorded with semimicro-electrodes) were not different in Holmes-Adie-patients with areflexia and normals."} {"id": "PMID:165140", "title": "Cyclic adenosine 3':5'-monophosphate and inhibition of deoxyribonucleic acid synthesis in vitro.", "content": "Results are presented which suggest that inhibition of tritiated thymidine incorporation into the deoxyribonucleic acid of bone marrow in vitro by high concentrations of cyclic adenosine 3':5'-monophosphate is pharmacological in nature, and thus apparently unrelated to the physiological actions of cAMP.", "contents": "Cyclic adenosine 3':5'-monophosphate and inhibition of deoxyribonucleic acid synthesis in vitro. Results are presented which suggest that inhibition of tritiated thymidine incorporation into the deoxyribonucleic acid of bone marrow in vitro by high concentrations of cyclic adenosine 3':5'-monophosphate is pharmacological in nature, and thus apparently unrelated to the physiological actions of cAMP."} {"id": "PMID:165141", "title": "Organ cultures of rat and hamster colon.", "content": "Human fibrin foam as a matrix for three-dimensional organ cultures was successfully employed for the cultivation of newborn rat and hamster colon tissue. Colonic tissue was maintained under different oxygen atmospheres and with various synthetic media. Explants of rat and hamster colon, maintained in Leibovitz's L-15 medium buffered with HEPES in the presence of 5% CO2 and air, retained their normal columnar epithelial architecture for 24 days in culture. Outgrowth of epithelial cells from colonic explants similar to those of the mother fragments grew into the foam. Viability of the explants was indicated by radioactive thymidine incorporation, and by the ability of the fragments to support viral replication.", "contents": "Organ cultures of rat and hamster colon. Human fibrin foam as a matrix for three-dimensional organ cultures was successfully employed for the cultivation of newborn rat and hamster colon tissue. Colonic tissue was maintained under different oxygen atmospheres and with various synthetic media. Explants of rat and hamster colon, maintained in Leibovitz's L-15 medium buffered with HEPES in the presence of 5% CO2 and air, retained their normal columnar epithelial architecture for 24 days in culture. Outgrowth of epithelial cells from colonic explants similar to those of the mother fragments grew into the foam. Viability of the explants was indicated by radioactive thymidine incorporation, and by the ability of the fragments to support viral replication."} {"id": "PMID:165146", "title": "Type-C virus-specific nucleic acid sequences in cultured rat cells.", "content": "Single-stranded DNA transcripts of rat type-C viruses prepared in the presence of actinomycin D, hybridized specifically to DNA of several rat cell cultures with no obvious qualitative or quantitative differences. Similar products prepared from a pseudo-type sarcoma virus with contributions from rat and mouse type-C viruses hybridized to both rat and mouse cellular DNA, while mouse viral transcripts did not hybridize to rat cell DNA. Viral RNA was detected in all rat cells by means of the rat viral DNA transcripts, with some differences between untreated low-passage cells and sister cultures treated with bromodeoxyuridine or bromodeoxyuridine and methylcholanthrene. Cells treated with both compounds were previously shown to be transformed and turorigenic, and these were distinguishable by kinetic analysis from the control cells.", "contents": "Type-C virus-specific nucleic acid sequences in cultured rat cells. Single-stranded DNA transcripts of rat type-C viruses prepared in the presence of actinomycin D, hybridized specifically to DNA of several rat cell cultures with no obvious qualitative or quantitative differences. Similar products prepared from a pseudo-type sarcoma virus with contributions from rat and mouse type-C viruses hybridized to both rat and mouse cellular DNA, while mouse viral transcripts did not hybridize to rat cell DNA. Viral RNA was detected in all rat cells by means of the rat viral DNA transcripts, with some differences between untreated low-passage cells and sister cultures treated with bromodeoxyuridine or bromodeoxyuridine and methylcholanthrene. Cells treated with both compounds were previously shown to be transformed and turorigenic, and these were distinguishable by kinetic analysis from the control cells."} {"id": "PMID:165147", "title": "Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus). III. Serological and biochemical findings in an animal with reticuloproliferative disease.", "content": "Nucleic acid hybridization with EB virus complementary RNA has demonstrated unequivocally that EB virus DNA is present in the cells of a continuous lymphoblastoid line established in culture from a pathological lymph node of an owl monkey with reticuloproliferative disease after inoculation with EB virus. There were 48 to 49 EB virus genome equivalents per cell. In addition, serological studies showed that the diseased owl monkey developed specific antibodies to EB virus capsid antigens. The antibodies were first detected by indirect immunofluorescence in serum sampled 13 weeks after inoculation, and were not found in sera from other animals without the disease. None of the monkeys developed heterophile antibodies. The significance of the biochemical and serological findings is discussed in relation to the nature of the reticuloproliferative disease and the possibility of tumour-induction by EB virus.", "contents": "Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus). III. Serological and biochemical findings in an animal with reticuloproliferative disease. Nucleic acid hybridization with EB virus complementary RNA has demonstrated unequivocally that EB virus DNA is present in the cells of a continuous lymphoblastoid line established in culture from a pathological lymph node of an owl monkey with reticuloproliferative disease after inoculation with EB virus. There were 48 to 49 EB virus genome equivalents per cell. In addition, serological studies showed that the diseased owl monkey developed specific antibodies to EB virus capsid antigens. The antibodies were first detected by indirect immunofluorescence in serum sampled 13 weeks after inoculation, and were not found in sera from other animals without the disease. None of the monkeys developed heterophile antibodies. The significance of the biochemical and serological findings is discussed in relation to the nature of the reticuloproliferative disease and the possibility of tumour-induction by EB virus."} {"id": "PMID:165148", "title": "Non-producer human cells induced by murine sarcoma virus.", "content": "Non-produces (NP) human cells were isolated from transformed foci induced by the Kirsten mouse sarcoma virus. These morphologically altered NP cells produced neither infectious virus nor complement-fixing antigens of the murine sarcoma-leukemia virus complex. However, the sarcoma virus genome could be rescued from these NF cells by co-cultivation with cells carrying \"helper\" Kirsten mouse leukemia virus or Woolly Monkey leukemia virus. The possible usefulness of these cells in efforts designed to detect covert or repressed RNA tumor viruses in various animal and human tissues is discussed.", "contents": "Non-producer human cells induced by murine sarcoma virus. Non-produces (NP) human cells were isolated from transformed foci induced by the Kirsten mouse sarcoma virus. These morphologically altered NP cells produced neither infectious virus nor complement-fixing antigens of the murine sarcoma-leukemia virus complex. However, the sarcoma virus genome could be rescued from these NF cells by co-cultivation with cells carrying \"helper\" Kirsten mouse leukemia virus or Woolly Monkey leukemia virus. The possible usefulness of these cells in efforts designed to detect covert or repressed RNA tumor viruses in various animal and human tissues is discussed."} {"id": "PMID:165149", "title": "Occurrence of nervous-tissue tumors in cattle, horses, cats and dogs.", "content": "From 11 North American veterinary university hospitals and clinics, 248 animals were a confirmed diagnosis of nervous-tissue tumor were identified; 7 tumors were found in cattle, 28 in horses, 14 in cats, 199 in dogs, and none in other species. Tumors were divided for analysis into three categories-glial, meningeal, and peripheral nerve. In cattle and horses, all tumors involved peripheral nerves, the risk of which, in horses, reached a plateau at 4-6 years of age and remained constant thereafter. In cats, the tumors were equally distributed among the three tumor categories whereas, in dogs, twice as many glial tumors as meningeal and peripheral nerve tumors were found. The risk for glial tumors in dogs reached a peak at 10-14 years of age, for meningeal at 7-9 years, and for peripheral nerve at 2-3 and 7-9 years. Three canine breeds-English bulldog, boxer, and Boston terrier-had an excessive rish of glial tumors. Except for an excess of skin tumors in dogs with peripheral nerve tumors, there was no unusual occurrence with second primary neoplasms for any species. There was no detectable predisposition by sex for any of the categories of nervous-tissue tumors among any of the four species. The role of genetic abnormalities associated with nervous-tissue tumors and other etiologic factors (e.g., chronic hypoxia) may be clarified by further studies involving canine breeds of \"bulldog\" ancestry.", "contents": "Occurrence of nervous-tissue tumors in cattle, horses, cats and dogs. From 11 North American veterinary university hospitals and clinics, 248 animals were a confirmed diagnosis of nervous-tissue tumor were identified; 7 tumors were found in cattle, 28 in horses, 14 in cats, 199 in dogs, and none in other species. Tumors were divided for analysis into three categories-glial, meningeal, and peripheral nerve. In cattle and horses, all tumors involved peripheral nerves, the risk of which, in horses, reached a plateau at 4-6 years of age and remained constant thereafter. In cats, the tumors were equally distributed among the three tumor categories whereas, in dogs, twice as many glial tumors as meningeal and peripheral nerve tumors were found. The risk for glial tumors in dogs reached a peak at 10-14 years of age, for meningeal at 7-9 years, and for peripheral nerve at 2-3 and 7-9 years. Three canine breeds-English bulldog, boxer, and Boston terrier-had an excessive rish of glial tumors. Except for an excess of skin tumors in dogs with peripheral nerve tumors, there was no unusual occurrence with second primary neoplasms for any species. There was no detectable predisposition by sex for any of the categories of nervous-tissue tumors among any of the four species. The role of genetic abnormalities associated with nervous-tissue tumors and other etiologic factors (e.g., chronic hypoxia) may be clarified by further studies involving canine breeds of \"bulldog\" ancestry."} {"id": "PMID:165150", "title": "Infectious DNA recovered from avian tumor-virus-producing cells.", "content": "A single treatment of chick embryo fibroblasts with DNA recovered from chick embryo fibroblasts productively infected and transformed with four different strains of RSV, or productively infected with two different strains of RAV, resulted in virus production and cell transformation (in the case of RSV) two or three passages after treatment (8-25 days). The virus recovered from cultures was phenotypically identical to that produced by the donor cells. No virus production nor cell transformation resulted from treatment of control cultures with DNA digested with DNAse. Infectious RSV-DNA was recovered from purified donor cell nuclei and was associated with the precipitable fraction of DNA prepared according to the method of Hirt (1967). It also sedimented with cellular DNA in density gradients, and with high molecular weight DNA (2-4 times 10-7 daltons) in sucrose gradients, which suggests that it is associated and may be integrated with chromosomal DNA. In some experiments, DNA fractions of lower molecular weight (down to 6 times 10-6 daltons) were also infectious. DNA from virus-producing RSV-transformed cells also gave rise to virus and Rous cells in cultures of fibroblasts from gs- embryos. However, the amount of DNA required for successful infection varied widely between experiments, and no reproducible dose-effect relationship was observed. The frequency of DNA-treated cells which produced virus remained low, even when the assay cultures were pretreated with 5-bromodeoxyuridine.", "contents": "Infectious DNA recovered from avian tumor-virus-producing cells. A single treatment of chick embryo fibroblasts with DNA recovered from chick embryo fibroblasts productively infected and transformed with four different strains of RSV, or productively infected with two different strains of RAV, resulted in virus production and cell transformation (in the case of RSV) two or three passages after treatment (8-25 days). The virus recovered from cultures was phenotypically identical to that produced by the donor cells. No virus production nor cell transformation resulted from treatment of control cultures with DNA digested with DNAse. Infectious RSV-DNA was recovered from purified donor cell nuclei and was associated with the precipitable fraction of DNA prepared according to the method of Hirt (1967). It also sedimented with cellular DNA in density gradients, and with high molecular weight DNA (2-4 times 10-7 daltons) in sucrose gradients, which suggests that it is associated and may be integrated with chromosomal DNA. In some experiments, DNA fractions of lower molecular weight (down to 6 times 10-6 daltons) were also infectious. DNA from virus-producing RSV-transformed cells also gave rise to virus and Rous cells in cultures of fibroblasts from gs- embryos. However, the amount of DNA required for successful infection varied widely between experiments, and no reproducible dose-effect relationship was observed. The frequency of DNA-treated cells which produced virus remained low, even when the assay cultures were pretreated with 5-bromodeoxyuridine."} {"id": "PMID:165151", "title": "Activation of carcinogenic polycyclic hydrocarbons in polyoma-virus-transformed cells as a prerequisite for polyoma virus induction.", "content": "Polyoma-virus (PV)-transformed cell clones, which are inducible for virus synthesis by various physical and chemical agents, metabolize the chemically non-reactive carcinogen benzo(a)pyrene (BP) into water soluble products. In cultures of such clones, which metabolize BP to a level of 30-6-% of that of normal cells, up to 10.4% of the cells were induced for PV synthesis by BP, 20-methylcholanthrene (MCA) and 7,12-dimethylbenz(a)anthracene (CMBA). No PV induction was observed with the non-carcinogenic polycyclic hydrocarbons pyrene chrysene and benz(a)-anthracene. A proportion of subclones, isolated from a PV- inducible clone, which metabolized 0.1 mug or less BP per 10-6 cells were all inducible for PV synthesis by these carcinogens. Subclones isolated from an inducible clone pretreated with BP were shown to metabolize less than 0.1 mu BP per 10-6 cells and were resistant to virus induction by the carcinogenic polycyclic hydrocarbons. Benzoflavone, which inhibited the metabolism of BP in clones metabolizing high levels of this carcinogen, also prevented the induction of PV antigen and infectious virus synthesis in these clones. The data indicate a relationship between the carcinogenicity of polycyclic hydrocarbons and their ability to induce virus in the PV-transformed cells and suggest that virus induction depends on metabolic conversion of these hydrocarbons into similar reactive compounds that are responsible for malignant transformation and mutagenesis.", "contents": "Activation of carcinogenic polycyclic hydrocarbons in polyoma-virus-transformed cells as a prerequisite for polyoma virus induction. Polyoma-virus (PV)-transformed cell clones, which are inducible for virus synthesis by various physical and chemical agents, metabolize the chemically non-reactive carcinogen benzo(a)pyrene (BP) into water soluble products. In cultures of such clones, which metabolize BP to a level of 30-6-% of that of normal cells, up to 10.4% of the cells were induced for PV synthesis by BP, 20-methylcholanthrene (MCA) and 7,12-dimethylbenz(a)anthracene (CMBA). No PV induction was observed with the non-carcinogenic polycyclic hydrocarbons pyrene chrysene and benz(a)-anthracene. A proportion of subclones, isolated from a PV- inducible clone, which metabolized 0.1 mug or less BP per 10-6 cells were all inducible for PV synthesis by these carcinogens. Subclones isolated from an inducible clone pretreated with BP were shown to metabolize less than 0.1 mu BP per 10-6 cells and were resistant to virus induction by the carcinogenic polycyclic hydrocarbons. Benzoflavone, which inhibited the metabolism of BP in clones metabolizing high levels of this carcinogen, also prevented the induction of PV antigen and infectious virus synthesis in these clones. The data indicate a relationship between the carcinogenicity of polycyclic hydrocarbons and their ability to induce virus in the PV-transformed cells and suggest that virus induction depends on metabolic conversion of these hydrocarbons into similar reactive compounds that are responsible for malignant transformation and mutagenesis."} {"id": "PMID:165152", "title": "Transformation of horse skin cells by type-C sarcoma viruses.", "content": "A horse skin cell line (E. Derm, NBL-6, CCL-57) was susceptible to focus formation by the Kirsten mouse sarcoma virus, feline sarcoma virus (ST stain) and the MSV pseudotypes with woolly monkey, gibbon monkey, RD-114, AT-124, baboon placenta and murine xenotropic (BALB/c 3T3 and C57L/JD) type-C viruses. Foci were detected within 5 days after infection and the transformed cells continued to produce infectious virus and group-specific antigen of their respective type-C leukemia viruses. The transformation efficiency of various type-C sarcoma viruses in horse cells was also very high.", "contents": "Transformation of horse skin cells by type-C sarcoma viruses. A horse skin cell line (E. Derm, NBL-6, CCL-57) was susceptible to focus formation by the Kirsten mouse sarcoma virus, feline sarcoma virus (ST stain) and the MSV pseudotypes with woolly monkey, gibbon monkey, RD-114, AT-124, baboon placenta and murine xenotropic (BALB/c 3T3 and C57L/JD) type-C viruses. Foci were detected within 5 days after infection and the transformed cells continued to produce infectious virus and group-specific antigen of their respective type-C leukemia viruses. The transformation efficiency of various type-C sarcoma viruses in horse cells was also very high."} {"id": "PMID:165153", "title": "Demonstration of oncogenic potential of mammalian cells transformed by DNA-containing viruses following photodynamic inactivation.", "content": "The oncogenic properties of hamster embryo cells transformed by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and SV40 virus following photodynamic inactivation using neutral red were determined by subcutaneous inoculation into newborn Syrian hamsters. Cells transformed by all three viruses produced palpable tumors after different latent periods. Histopathological examination showed that HSV-2 tumors were fibrosarcomas and metastases were often seen in the lungs. HSV-2 primary tumors were reinoculated subcutaneously into weanling hamsters; they developed palpable tumors within 2 weeks. HSV-specific antigens were detected in the cytoplasm and/or on the surface of both the HSV-1 and HSV-2 tumor-cell cultures by the indirect immunofluorescence technique. The same method revealed SV40 tumor antigen in the nuclei of the SV40 tumor cells. Sera from HSV or SV40 tumor-bearing hamsters gave positive reactions when tested against HSV-infected hamster cells or SV40-infected monkey cells, respectively. These results demonstrate that herpes simplex virus and SV40, whose infectivity was lost following photodynamic inactivation, retained the virus genetic information necessary for transformation of normal cells to an oncogenic phenotype.", "contents": "Demonstration of oncogenic potential of mammalian cells transformed by DNA-containing viruses following photodynamic inactivation. The oncogenic properties of hamster embryo cells transformed by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and SV40 virus following photodynamic inactivation using neutral red were determined by subcutaneous inoculation into newborn Syrian hamsters. Cells transformed by all three viruses produced palpable tumors after different latent periods. Histopathological examination showed that HSV-2 tumors were fibrosarcomas and metastases were often seen in the lungs. HSV-2 primary tumors were reinoculated subcutaneously into weanling hamsters; they developed palpable tumors within 2 weeks. HSV-specific antigens were detected in the cytoplasm and/or on the surface of both the HSV-1 and HSV-2 tumor-cell cultures by the indirect immunofluorescence technique. The same method revealed SV40 tumor antigen in the nuclei of the SV40 tumor cells. Sera from HSV or SV40 tumor-bearing hamsters gave positive reactions when tested against HSV-infected hamster cells or SV40-infected monkey cells, respectively. These results demonstrate that herpes simplex virus and SV40, whose infectivity was lost following photodynamic inactivation, retained the virus genetic information necessary for transformation of normal cells to an oncogenic phenotype."} {"id": "PMID:165154", "title": "Characteristics of cell lines derived from human leukocytes transformed by different strains of Epstein-Barr virus.", "content": "Variation of Epstein-Barr virus (EBV) in respect to its effect on the properties of transformed cells was probed. Human umbilical cord leukocytes from six different individuals were transformed in vitro by either B95-8 (B) or QIMR-WIL (Q) strains of EBV and subsequently 12 lymphoblastoid cell lines (six B-derived and six Q-derived lines) were established. The B lines and Q lines were different in the expression of EBV genome i.e. production of virus or viral antigens, and in other properties including growth pattern and immunoglobulin production. The most striking differences between the two groups lay in their capacity to produce infectious virus and in the shape of the cell-clumps. The results suggest that different strains of EBV may induce transformed cells with different characteristics.", "contents": "Characteristics of cell lines derived from human leukocytes transformed by different strains of Epstein-Barr virus. Variation of Epstein-Barr virus (EBV) in respect to its effect on the properties of transformed cells was probed. Human umbilical cord leukocytes from six different individuals were transformed in vitro by either B95-8 (B) or QIMR-WIL (Q) strains of EBV and subsequently 12 lymphoblastoid cell lines (six B-derived and six Q-derived lines) were established. The B lines and Q lines were different in the expression of EBV genome i.e. production of virus or viral antigens, and in other properties including growth pattern and immunoglobulin production. The most striking differences between the two groups lay in their capacity to produce infectious virus and in the shape of the cell-clumps. The results suggest that different strains of EBV may induce transformed cells with different characteristics."} {"id": "PMID:165155", "title": "BCG therapy of pleural and peritoneal growth of transplanted rat tumours.", "content": "Growth of intrapleurally injected cells of immunogenic methylcholanthrene-induced rat sarcomas was suppressed by intrapleural injection of viable or 1 times 10-6 R radiation-sterilized BCG vaccine. As little as 10 mug moist weight of organisms was effective, and treatment could be given several days before or after tumour challenge. Pleural effusion growth of a moderately immunogenic ascitic hepatoma was also controlled by intrapleurally administered BCG. In contrast, BCG injected intravenously, subcutaneously or intraperitoneally was without influence on pleural tumour growths. Similarly, intraperitoneal growth of these tumours was suppressed only by intraperitoneal injection of BCG. With two other transplanted tumours, a chemically induced mammary carcinoma and a spontaneous sarcoma, both of which lack significant immunogenicity, BCG treatment of pleural and peritoneal growths was less successful and more variable. Nevertheless, these studies indicate the potential of this type of treatment of thoracic and peritoneal tumour deposits for possible clinical application in the treatment of malignant mesothelioma.", "contents": "BCG therapy of pleural and peritoneal growth of transplanted rat tumours. Growth of intrapleurally injected cells of immunogenic methylcholanthrene-induced rat sarcomas was suppressed by intrapleural injection of viable or 1 times 10-6 R radiation-sterilized BCG vaccine. As little as 10 mug moist weight of organisms was effective, and treatment could be given several days before or after tumour challenge. Pleural effusion growth of a moderately immunogenic ascitic hepatoma was also controlled by intrapleurally administered BCG. In contrast, BCG injected intravenously, subcutaneously or intraperitoneally was without influence on pleural tumour growths. Similarly, intraperitoneal growth of these tumours was suppressed only by intraperitoneal injection of BCG. With two other transplanted tumours, a chemically induced mammary carcinoma and a spontaneous sarcoma, both of which lack significant immunogenicity, BCG treatment of pleural and peritoneal growths was less successful and more variable. Nevertheless, these studies indicate the potential of this type of treatment of thoracic and peritoneal tumour deposits for possible clinical application in the treatment of malignant mesothelioma."} {"id": "PMID:165156", "title": "Classification and biological nature of established human hematopoietic cell lines.", "content": "Over 200 established human hematopoietic cell lines of normal and malignant origin have been investigated by morphological and functional parameters. Employing morphology as the overriding parameter four types of lines were identified. (1) Lymphoblastoid cell lines, derived from normal and neoplastic hematopoietic tissue, were characterized by the wide morphologic flexibility of individual lymphoblastoid cells, constant association with Epstein-Barr virus (EBV), polyclonal derivation, differentiation for immunoglobulin production (secretion) and their diploids. (2) Lymphoma cell lines. This type of line was established at a high frequency from Burkitt's lymphoma and rarely from other types of lymphoma, but never from patients without malignancy or with non-lymphoma malignancies. Important characteristics were morphologic stereotypia within each line, monoclonal derivation, common but not obligatory association with EBV, variability in the expression of Ig synthesis (no production, or membrane bound Ig, or secretion) and aneuploidy. (3) Myeloma cell lines could only rarely be obtained from patients with myeloma. The basis for classification of these lines is their production of Ig identical to the myeloma protein in vitro. Other important distinguishing features were: plasma cell morphology, absence of EBV and aneuploidy. (4) The leukemia cell line (MOLT 4) was the only line with T-cell characteristics and was easily distinguished from the other types. Important characteristics were a typical surface ultrastructure, absence of EBV and absence of immunoglobulin production, Individual lymphoblastoid lines were in principle identical whereas each line of the other three types had its own characteristic profile. The phenotypic characteristics of the lymphoblastoid lines were very stable during prolonged serial cultivation. Only in a few cases were secondary chromosomal, functional or morphologic alterations noted. We conclude that EBV-carrying lymphoblastoid lines can be obtained from non-neoplastic precursor cells from healthy as well as from diseased individuals. Lymphoma, myeloma and leukemia lines are only obtained from the respective neoplastic tissue but generally at a low frequency. With the exception of Burkitt's lymphoma, malignant hematopoietic tissue and leukemia frequently give rise to established cell lines in vitro of the lymphoblastoid type rather than lines derived from the neoplastic cells;", "contents": "Classification and biological nature of established human hematopoietic cell lines. Over 200 established human hematopoietic cell lines of normal and malignant origin have been investigated by morphological and functional parameters. Employing morphology as the overriding parameter four types of lines were identified. (1) Lymphoblastoid cell lines, derived from normal and neoplastic hematopoietic tissue, were characterized by the wide morphologic flexibility of individual lymphoblastoid cells, constant association with Epstein-Barr virus (EBV), polyclonal derivation, differentiation for immunoglobulin production (secretion) and their diploids. (2) Lymphoma cell lines. This type of line was established at a high frequency from Burkitt's lymphoma and rarely from other types of lymphoma, but never from patients without malignancy or with non-lymphoma malignancies. Important characteristics were morphologic stereotypia within each line, monoclonal derivation, common but not obligatory association with EBV, variability in the expression of Ig synthesis (no production, or membrane bound Ig, or secretion) and aneuploidy. (3) Myeloma cell lines could only rarely be obtained from patients with myeloma. The basis for classification of these lines is their production of Ig identical to the myeloma protein in vitro. Other important distinguishing features were: plasma cell morphology, absence of EBV and aneuploidy. (4) The leukemia cell line (MOLT 4) was the only line with T-cell characteristics and was easily distinguished from the other types. Important characteristics were a typical surface ultrastructure, absence of EBV and absence of immunoglobulin production, Individual lymphoblastoid lines were in principle identical whereas each line of the other three types had its own characteristic profile. The phenotypic characteristics of the lymphoblastoid lines were very stable during prolonged serial cultivation. Only in a few cases were secondary chromosomal, functional or morphologic alterations noted. We conclude that EBV-carrying lymphoblastoid lines can be obtained from non-neoplastic precursor cells from healthy as well as from diseased individuals. Lymphoma, myeloma and leukemia lines are only obtained from the respective neoplastic tissue but generally at a low frequency. With the exception of Burkitt's lymphoma, malignant hematopoietic tissue and leukemia frequently give rise to established cell lines in vitro of the lymphoblastoid type rather than lines derived from the neoplastic cells;"} {"id": "PMID:165159", "title": "Carcinoma of the stomach.", "content": "Seventy-five cases of stomach carcinoma were analyzed. The incidence was highest between 41 and 50 years of age. Male to female ratio was 4:1. The average duration of symptoms was one year. There was no correlation between incidence and the dietary and smoking habits of the patients. Epigastric pain was the commonest complaint followed byanorexis, vomiting and loss of weight. Anemia was the commonest finding. Epigastric mass was present in nearly 50% of cases. Pyloric obstruction was common. Upper gastrointestinal x-ray studies were rewarding. Occult blood was often found in the stools. The majority of patients were about equally distributed between blood groups A and O. Many patients had no or low acid levels but 7.5% had normal or high acid levels. At operation, the growth was commonly found near the pylorus. Diffuse involvement was infrequent. Curative surgery could be done in only 20% of cases. One-third of the patients had palliative gastrojejunostomy. The operative mortality and morbidity were high. The overall five-year survival was only 5%.", "contents": "Carcinoma of the stomach. Seventy-five cases of stomach carcinoma were analyzed. The incidence was highest between 41 and 50 years of age. Male to female ratio was 4:1. The average duration of symptoms was one year. There was no correlation between incidence and the dietary and smoking habits of the patients. Epigastric pain was the commonest complaint followed byanorexis, vomiting and loss of weight. Anemia was the commonest finding. Epigastric mass was present in nearly 50% of cases. Pyloric obstruction was common. Upper gastrointestinal x-ray studies were rewarding. Occult blood was often found in the stools. The majority of patients were about equally distributed between blood groups A and O. Many patients had no or low acid levels but 7.5% had normal or high acid levels. At operation, the growth was commonly found near the pylorus. Diffuse involvement was infrequent. Curative surgery could be done in only 20% of cases. One-third of the patients had palliative gastrojejunostomy. The operative mortality and morbidity were high. The overall five-year survival was only 5%."} {"id": "PMID:165160", "title": "Primary cerebral neoplasia in Rhodesia.", "content": "In 17 years we have performed 6,505 neurosurgical procedures in the neurosurgical unit of the Salisbury Hospital Group. Only 62% were performed on Africanpatients and 38% on European patients, despite the fact that the African population exceeds the European population by 20 times. This is partly due to the tolerance of rural people towards disease and partly to a number of social factors. The European group has a greater percentage of elderly people than the African group and, although we could not estimate the incidence of tumors among the African group, we would expect their overall incidence per capita to be lower because malignant tumors tend to occur in older people. We do not suspect the existence of a genetic factor in tumor incidence. There were 205 primary intracranial neoplasms in Africans and 244 in Europeans. Histological study shows that 33% of all tumors were meningiomas in the African group compared to 19% in the European group. Gliomas comprised 61.3% of the European series and 48.8% of the African series but the distribution by Kernohan's grading of astrocytomas was the same in both groups. If age was a factor, Grades I and II should have predominated in the African group, but did not. The incidence for each tumor among our European patients followed the patterns reported in various European and USA series. Likewise the pattern emerging from our African series closely paralleled the reports of other workers in Africa. Acoustic neuromas appear to be rather rare among Africans. The average age of all adults with tumors was 15 years lower in the African group than in the European group. However, this is entirely related to the age structure of the population, and not to an earlier age of occurrence. The average ages of medulloblastoma cases were identical. In our European series the occurrence according to age was much the same as that reported by overseas workers. The sex incidence of tumors in the European group seems to be a fair reflection of the situation elsewhere; in the African group it is questionable because men go into the towns to work and leave their families in the country. There was no significant difference in the location of tumors in the two groups. Results of treatment were uniformly inferior in the African group, partly due to the lateness of arrival at the hospital so that the growth was already far advanced and also because many patients suffered poor health from concomitant disease.", "contents": "Primary cerebral neoplasia in Rhodesia. In 17 years we have performed 6,505 neurosurgical procedures in the neurosurgical unit of the Salisbury Hospital Group. Only 62% were performed on Africanpatients and 38% on European patients, despite the fact that the African population exceeds the European population by 20 times. This is partly due to the tolerance of rural people towards disease and partly to a number of social factors. The European group has a greater percentage of elderly people than the African group and, although we could not estimate the incidence of tumors among the African group, we would expect their overall incidence per capita to be lower because malignant tumors tend to occur in older people. We do not suspect the existence of a genetic factor in tumor incidence. There were 205 primary intracranial neoplasms in Africans and 244 in Europeans. Histological study shows that 33% of all tumors were meningiomas in the African group compared to 19% in the European group. Gliomas comprised 61.3% of the European series and 48.8% of the African series but the distribution by Kernohan's grading of astrocytomas was the same in both groups. If age was a factor, Grades I and II should have predominated in the African group, but did not. The incidence for each tumor among our European patients followed the patterns reported in various European and USA series. Likewise the pattern emerging from our African series closely paralleled the reports of other workers in Africa. Acoustic neuromas appear to be rather rare among Africans. The average age of all adults with tumors was 15 years lower in the African group than in the European group. However, this is entirely related to the age structure of the population, and not to an earlier age of occurrence. The average ages of medulloblastoma cases were identical. In our European series the occurrence according to age was much the same as that reported by overseas workers. The sex incidence of tumors in the European group seems to be a fair reflection of the situation elsewhere; in the African group it is questionable because men go into the towns to work and leave their families in the country. There was no significant difference in the location of tumors in the two groups. Results of treatment were uniformly inferior in the African group, partly due to the lateness of arrival at the hospital so that the growth was already far advanced and also because many patients suffered poor health from concomitant disease."} {"id": "PMID:165157", "title": "Genital herpes: Treatment with methylene blue and light exposure.", "content": "Fifty-six patients with genital herpes were treated by photodynamic inactivation of herpesvirus by methylene blue (36 patients), proflavine (101 or neutral red (10). The first 35 patients were randomly selected for treatment with one of the three dyes. All the others were initially treated with methylene blue. The disease was temporarily eradicated in about 70% of instances by exposure of the lesions to light plus topically applied methylene blue, neutral red or proflavine. Relapses, however, were not prevented or appreciably reduced.", "contents": "Genital herpes: Treatment with methylene blue and light exposure. Fifty-six patients with genital herpes were treated by photodynamic inactivation of herpesvirus by methylene blue (36 patients), proflavine (101 or neutral red (10). The first 35 patients were randomly selected for treatment with one of the three dyes. All the others were initially treated with methylene blue. The disease was temporarily eradicated in about 70% of instances by exposure of the lesions to light plus topically applied methylene blue, neutral red or proflavine. Relapses, however, were not prevented or appreciably reduced."} {"id": "PMID:165163", "title": "The mucosubstance coating the pneumonocytes in the lungs of Xenopus laevis and Lacerta viridis.", "content": "The layer of mucosubstance that is associated with the free surface membranes of the pneumonocytes in the lungs of the toad Xenopus laevis and the lizard Lacerta viridis was demonstrated by electron microscopy using iron oxide stain. The form and staining reactions of the mucosubstance layer were similar in both animals. In electron micrographs the mucosubstance was represented by a band of densely stained material (25-50 nm thick) which coated the entire free surface of the pneumonocytes. It appeared to be firmly attached to the outer leaflet of the superficial plasma membrane. Short lengths of osmiophilic membranes, presumed to be fragments of pulmonary surfactant, were often observed lying free in the air spaces but they did not show any affinity for iron stain. Incubation of lung sections in a solution of neuraminidase produced a marked decrease in the intensity of the surface staining; no change was detected after incubation in trypsin, papain, hyaluronidase, N-acetyl cysteine, or phosphate buffer. It is, therefore, concluded that the pneumonocyte surface coat consists mainly of a sialomucin.", "contents": "The mucosubstance coating the pneumonocytes in the lungs of Xenopus laevis and Lacerta viridis. The layer of mucosubstance that is associated with the free surface membranes of the pneumonocytes in the lungs of the toad Xenopus laevis and the lizard Lacerta viridis was demonstrated by electron microscopy using iron oxide stain. The form and staining reactions of the mucosubstance layer were similar in both animals. In electron micrographs the mucosubstance was represented by a band of densely stained material (25-50 nm thick) which coated the entire free surface of the pneumonocytes. It appeared to be firmly attached to the outer leaflet of the superficial plasma membrane. Short lengths of osmiophilic membranes, presumed to be fragments of pulmonary surfactant, were often observed lying free in the air spaces but they did not show any affinity for iron stain. Incubation of lung sections in a solution of neuraminidase produced a marked decrease in the intensity of the surface staining; no change was detected after incubation in trypsin, papain, hyaluronidase, N-acetyl cysteine, or phosphate buffer. It is, therefore, concluded that the pneumonocyte surface coat consists mainly of a sialomucin."} {"id": "PMID:165164", "title": "A histochemical study of acid phosphatase in normal and virus-transformed cultured fibroblasts.", "content": "The distribution of acid phosphatase has been investigated in normal and virus-transformed cultured hamster and mouse fibroblasts. The enzyme was found to be present in lysosomes, autophagic vacuoles and elements of the Golgi apparatus. It was also found to be associated with a surface coat in some virus-transformed mouse cells and in the cytoplasm of both normal and transformed hamster cells.", "contents": "A histochemical study of acid phosphatase in normal and virus-transformed cultured fibroblasts. The distribution of acid phosphatase has been investigated in normal and virus-transformed cultured hamster and mouse fibroblasts. The enzyme was found to be present in lysosomes, autophagic vacuoles and elements of the Golgi apparatus. It was also found to be associated with a surface coat in some virus-transformed mouse cells and in the cytoplasm of both normal and transformed hamster cells."} {"id": "PMID:165165", "title": "Indirect sulphonation of mucopolysaccharides and glycogen in tissue sections with the use of bisulphite or dithionite after periodic acid oxidation.", "content": "Tissue mucopolysaccharides and glycogen can be indirectly sulphated after being oxidized by periodic acid and treated with sodium bisulphite or dithionite in aqueous solution. The sulphated sites are darkly stained by Roluidine Blue and realted dyes at pH less than 1.0. The background is very pale or colourless. The stained sections resist extraction with 1% hydrochloric acid for 48 hr, but can be extracted by 5% ammonium hydroxide in ethanol in 1 hr. Other oxidizing agents cannot be substituted for periodic acid.", "contents": "Indirect sulphonation of mucopolysaccharides and glycogen in tissue sections with the use of bisulphite or dithionite after periodic acid oxidation. Tissue mucopolysaccharides and glycogen can be indirectly sulphated after being oxidized by periodic acid and treated with sodium bisulphite or dithionite in aqueous solution. The sulphated sites are darkly stained by Roluidine Blue and realted dyes at pH less than 1.0. The background is very pale or colourless. The stained sections resist extraction with 1% hydrochloric acid for 48 hr, but can be extracted by 5% ammonium hydroxide in ethanol in 1 hr. Other oxidizing agents cannot be substituted for periodic acid."} {"id": "PMID:165166", "title": "Response of solitary adrenal gland to surgical stress.", "content": "Available reports on adrenal function following unilateral adrenalectomy mainly concern the gland's activity under basal conditions. Its response to superadded stress has largely escaped attention. The present communication deals with changes in morphology and in the behavior of acid phosphatase, non-specific esterases and 3beta-hydroxysteroid dehydrogenase in solitary adrenal glands following operative trauma. Histochemical, electrophoretic and biochemical techniques have been employed in the study. Although the morphological response to identical trauma on both unilaterally adrenal-extomized and intact animals is indistinguishable, the enzymological response is strikingly different in the two groups. While in the latter, the enzyme activities exhibit an early rise following trauma, the same is delayed by another 8 hr in the former. In experments using ACTH, the overall pattern of exterase activity shows little deviation from that observed in untreated cases in both groups of animals. The findings indicate that in unilaterally adrenalectomized animals, susperadded operative stimuli fail to evoke the early response characteristic of the normal adrenal glands. Such latency points to the vulnerability of their existing defence mechanisms. The remarkable similarity of adrenal response with or without exogenous ACTH in these animals suggests that the reason for a delayed response is rooted in the target organ itself, and is not due to an altered plasma ACTH level.", "contents": "Response of solitary adrenal gland to surgical stress. Available reports on adrenal function following unilateral adrenalectomy mainly concern the gland's activity under basal conditions. Its response to superadded stress has largely escaped attention. The present communication deals with changes in morphology and in the behavior of acid phosphatase, non-specific esterases and 3beta-hydroxysteroid dehydrogenase in solitary adrenal glands following operative trauma. Histochemical, electrophoretic and biochemical techniques have been employed in the study. Although the morphological response to identical trauma on both unilaterally adrenal-extomized and intact animals is indistinguishable, the enzymological response is strikingly different in the two groups. While in the latter, the enzyme activities exhibit an early rise following trauma, the same is delayed by another 8 hr in the former. In experments using ACTH, the overall pattern of exterase activity shows little deviation from that observed in untreated cases in both groups of animals. The findings indicate that in unilaterally adrenalectomized animals, susperadded operative stimuli fail to evoke the early response characteristic of the normal adrenal glands. Such latency points to the vulnerability of their existing defence mechanisms. The remarkable similarity of adrenal response with or without exogenous ACTH in these animals suggests that the reason for a delayed response is rooted in the target organ itself, and is not due to an altered plasma ACTH level."} {"id": "PMID:165167", "title": "Localization in cardiac muscle of some enzymes related to glutamate metabolism.", "content": "A tetrazolium staining medium incorporated in a gel has been used in a histochemical study of enzymes in thin sections of heart muscle. Formazan distribution patterns given by mitochondrial enzymes were inconsistent with the location of these enzymes revealed by the extraction of whole tissue. Similar stain distributions were given by lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate dehydrogenase. The distribution given by succinate dehydrogenase was not the same as that given by cytochrome oxidase stained by a different technique. Alcohol dehydrogenase added to the tissue assumed a distribution which suggested some adsorption of the enzyme to the tissue. But experiments suggested that this enzyme was not firmly bound to muscle proteins in the manner of some glycolytic enzymes.", "contents": "Localization in cardiac muscle of some enzymes related to glutamate metabolism. A tetrazolium staining medium incorporated in a gel has been used in a histochemical study of enzymes in thin sections of heart muscle. Formazan distribution patterns given by mitochondrial enzymes were inconsistent with the location of these enzymes revealed by the extraction of whole tissue. Similar stain distributions were given by lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate dehydrogenase. The distribution given by succinate dehydrogenase was not the same as that given by cytochrome oxidase stained by a different technique. Alcohol dehydrogenase added to the tissue assumed a distribution which suggested some adsorption of the enzyme to the tissue. But experiments suggested that this enzyme was not firmly bound to muscle proteins in the manner of some glycolytic enzymes."} {"id": "PMID:165169", "title": "Isolation and characterization of mutants of Haemophilus influenzae deficient in an adenosine 5'-triphosphate-dependent deoxyribonuclease activity.", "content": "By a direct assay approach, mutants of Haemophilus influenzae Rd that are deficient in adenosine 5'-triphosphate-dependent deoxyribonuclease activity (add-) were isolated and characterized. A large proportion (50 to 90%) of the cells in cultures of these mutants failed to produce visible colonies when plated. An extensive analysis of the recombination proficiency of these strains revealed that the transformation frequency (transformants per competent cell) in the mutants was similar to that found in the wild type, but that the transformation efficiency (transformants per microgram of irreversibly bound deoxyribonucleic acid [DNA]) was reduced approximately fourfold. Sensitivities of the mutants to gamma rays, ultraviolet radiation, and methyl methane sulfonate were only slightly greater than wild-type levels. The rate of degradation of host DNA after ultraviolet irradiation was significantly reduced in the mutants. It is suggested that the adenosine 5'-triphosphate-dependent deoxyribonuclease in H. influenzae plays a nonessential role in DNA recombination and repair.", "contents": "Isolation and characterization of mutants of Haemophilus influenzae deficient in an adenosine 5'-triphosphate-dependent deoxyribonuclease activity. By a direct assay approach, mutants of Haemophilus influenzae Rd that are deficient in adenosine 5'-triphosphate-dependent deoxyribonuclease activity (add-) were isolated and characterized. A large proportion (50 to 90%) of the cells in cultures of these mutants failed to produce visible colonies when plated. An extensive analysis of the recombination proficiency of these strains revealed that the transformation frequency (transformants per competent cell) in the mutants was similar to that found in the wild type, but that the transformation efficiency (transformants per microgram of irreversibly bound deoxyribonucleic acid [DNA]) was reduced approximately fourfold. Sensitivities of the mutants to gamma rays, ultraviolet radiation, and methyl methane sulfonate were only slightly greater than wild-type levels. The rate of degradation of host DNA after ultraviolet irradiation was significantly reduced in the mutants. It is suggested that the adenosine 5'-triphosphate-dependent deoxyribonuclease in H. influenzae plays a nonessential role in DNA recombination and repair."} {"id": "PMID:165170", "title": "Adenosine 3',5'-cyclic monophosphate and morphology in Neurospora crassa: drug-induced alterations.", "content": "Grown in liquid culture in the presence of a variety of structurally unrelated drugs, mycelia of wild-type Neurospora assume a colonial or semicolonial growth habit similar to that of known morphological mutants. Drugs that produce these morphological changes include atropine, theophylline, histamine, and several of the quinoline-containing antimalarials. Each of these drugs decrease the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) concentration of mycelia as a result of their effect on the activity of adenyl cyclase, the cAMP-dependent phosphodiesterase, or both. The evidence indicates a relationship between the degree of morphological abnormality, the degree to which intracellular cAMP is reduced, and the action of the drugs on the adenyl cyclase and phosphodiesterase.", "contents": "Adenosine 3',5'-cyclic monophosphate and morphology in Neurospora crassa: drug-induced alterations. Grown in liquid culture in the presence of a variety of structurally unrelated drugs, mycelia of wild-type Neurospora assume a colonial or semicolonial growth habit similar to that of known morphological mutants. Drugs that produce these morphological changes include atropine, theophylline, histamine, and several of the quinoline-containing antimalarials. Each of these drugs decrease the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) concentration of mycelia as a result of their effect on the activity of adenyl cyclase, the cAMP-dependent phosphodiesterase, or both. The evidence indicates a relationship between the degree of morphological abnormality, the degree to which intracellular cAMP is reduced, and the action of the drugs on the adenyl cyclase and phosphodiesterase."} {"id": "PMID:165171", "title": "Regulation of galactose operon at the gal operator-promoter region in Escherichia coli K-12.", "content": "The capR (lon) product controls expression of the gal operon independently of the galR repressor. Previously, mutations of the gal operon have been isolated that are semiconstitutive and alter response to the capR and/or capT product. Such mutants imply the existence of a distinct site in the operon that responds to capR (capT) control. This mutation could be either in a site near the operator-distal end of the galE gene, which signals rho factor termination of transcription in vitro or in a site in the operator-promoter region. Bacteriophage U3 was used to isolate galE mutations in HC2142 (a mutant exhibiting reduced response to capR control). P1 transduction was used to cross these mutants with a set of galE gene deletion. Analysis of the resulting Gal+ recombinants indicates that the regulatory site is in the operator-promoter region. Hence, it is unlikely that capR functions in control as an anti-rho factor at the operator-distal end of the galE gene, but more likely as previously suggested, at a second operator distinct from one responding to galR repressor control. Upon induction with D-fucose, a promoter mutant (UV211) isolated previously expressed 20 to 30% of the galactose enzymes that the wild type exhibited in the presence of the inducer D-fucose. The effects of various mutations in cya, capR, and galR on galactokinase synthesis in this mutant were determined. Galactokinase was derepressed by capR as well as galR, but the presence or absence of the cya gene product was unimportant.", "contents": "Regulation of galactose operon at the gal operator-promoter region in Escherichia coli K-12. The capR (lon) product controls expression of the gal operon independently of the galR repressor. Previously, mutations of the gal operon have been isolated that are semiconstitutive and alter response to the capR and/or capT product. Such mutants imply the existence of a distinct site in the operon that responds to capR (capT) control. This mutation could be either in a site near the operator-distal end of the galE gene, which signals rho factor termination of transcription in vitro or in a site in the operator-promoter region. Bacteriophage U3 was used to isolate galE mutations in HC2142 (a mutant exhibiting reduced response to capR control). P1 transduction was used to cross these mutants with a set of galE gene deletion. Analysis of the resulting Gal+ recombinants indicates that the regulatory site is in the operator-promoter region. Hence, it is unlikely that capR functions in control as an anti-rho factor at the operator-distal end of the galE gene, but more likely as previously suggested, at a second operator distinct from one responding to galR repressor control. Upon induction with D-fucose, a promoter mutant (UV211) isolated previously expressed 20 to 30% of the galactose enzymes that the wild type exhibited in the presence of the inducer D-fucose. The effects of various mutations in cya, capR, and galR on galactokinase synthesis in this mutant were determined. Galactokinase was derepressed by capR as well as galR, but the presence or absence of the cya gene product was unimportant."} {"id": "PMID:165172", "title": "Two types of glucose effects on beta-galactosidase synthesis in a membrane fraction of Escherichia coli: correlation with repression observed in intact cells.", "content": "A membrane fraction obtained from an osmotic lysate of Escherichia coli spheroplasts retains capability to synthesize beta-galactosidase. The system also retains cellular regulatory functions, one of which is known as catabolite repression. Two types of repression of beta-galactosidase synthesis were observed in this membrane system: one was caused by the addition of 2-deoxyglucose or glucose at a low concentration (3 times 10- minus 4 M), and the other was caused by glucose-6-phosphate or glucose at a high concentration (3 times 10- minus 2 M). In the presence of cyclic adenosine 3',5'-monophosphate (10 mM), repression caused by the former was completely reversed, whereas repression by the latter was only partially reversed. Conditions in intact cells causing transient and permanent repression were also investigated. Upon addition of 2-deoxyglucose or glucose at a low concentration to intact cells, only transient repression of beta-galactosidase synthesis was observed. Glucose at a high concentration caused both transient and subsequent permanent repression, and intensity of permanent repression depended upon glucose concentration, whereas duration and intensity of transient repression were independent of glucose concentration. Mutants deficient in phosphoenolpyruvate-phosphotransferase system (Hpr minus and enzyme I minus) showed transient repression but failed to show permanent repression. In mutants deficient in glucose catabolism beyond glucose-6-phosphate, both transient and permanent repression were observed. Correlation between the observations in the membrane system and in intact cells is discussed. The results obtained here strongly suggest that transient repression is caused by glucose itself, and that permanent repression is caused by glucose-6-phosphate of high intracellular levels of glucose.", "contents": "Two types of glucose effects on beta-galactosidase synthesis in a membrane fraction of Escherichia coli: correlation with repression observed in intact cells. A membrane fraction obtained from an osmotic lysate of Escherichia coli spheroplasts retains capability to synthesize beta-galactosidase. The system also retains cellular regulatory functions, one of which is known as catabolite repression. Two types of repression of beta-galactosidase synthesis were observed in this membrane system: one was caused by the addition of 2-deoxyglucose or glucose at a low concentration (3 times 10- minus 4 M), and the other was caused by glucose-6-phosphate or glucose at a high concentration (3 times 10- minus 2 M). In the presence of cyclic adenosine 3',5'-monophosphate (10 mM), repression caused by the former was completely reversed, whereas repression by the latter was only partially reversed. Conditions in intact cells causing transient and permanent repression were also investigated. Upon addition of 2-deoxyglucose or glucose at a low concentration to intact cells, only transient repression of beta-galactosidase synthesis was observed. Glucose at a high concentration caused both transient and subsequent permanent repression, and intensity of permanent repression depended upon glucose concentration, whereas duration and intensity of transient repression were independent of glucose concentration. Mutants deficient in phosphoenolpyruvate-phosphotransferase system (Hpr minus and enzyme I minus) showed transient repression but failed to show permanent repression. In mutants deficient in glucose catabolism beyond glucose-6-phosphate, both transient and permanent repression were observed. Correlation between the observations in the membrane system and in intact cells is discussed. The results obtained here strongly suggest that transient repression is caused by glucose itself, and that permanent repression is caused by glucose-6-phosphate of high intracellular levels of glucose."} {"id": "PMID:165173", "title": "Effect of glucose and its analogues on the accumulation and release of cyclic adenosine 3',5'-monophosphate in a membrane fraction of Escherichia coli: relation to beta-galactosidase synthesis.", "content": "Correlation between beta-galactosidase synthesis and cyclic adenosine 3',5'-monophosphate (cAMP) levels in a membrane fraction obtained from disrupted spheroplasts of Escherichia coli was investigated. Repression of beta-galactosidase synthesis in the membrane fraction by glucose-6-phosphate and by 2-deoxyglucose differed in sensitivity to reversal by cAMP. The difference between the two repressions could be due to the fact that glucose-6-phosphate inhibited severely the accumulation of exogenous [3-H]cAMP by the membrane fraction, whereas 2-deoxyglucose had little effect on the accumulation of the nucleotide. On the other hand, a quick decrease in the level of [3-H]cAMP preaccumulated in the membrane fraction resulted from addition of either glucose-6-phosphate or 2-deoxyglucose. Results reported here suggest that repression of beta-galactosidase synthesis is associated with anabrupt decrease in cAMP levels at the intramembranal sites where beta-galactosidase is synthesized, and the major, if not sole, mechanism which leads to instantaneous drop of cAMP level is via the release of cAMP, but not by degradation of the nucleotide since the membrane fraction retained less than 10 percent of cellular cyclic phosphodiesterase and the activity of the enzyme was not affected by repressing sugars.", "contents": "Effect of glucose and its analogues on the accumulation and release of cyclic adenosine 3',5'-monophosphate in a membrane fraction of Escherichia coli: relation to beta-galactosidase synthesis. Correlation between beta-galactosidase synthesis and cyclic adenosine 3',5'-monophosphate (cAMP) levels in a membrane fraction obtained from disrupted spheroplasts of Escherichia coli was investigated. Repression of beta-galactosidase synthesis in the membrane fraction by glucose-6-phosphate and by 2-deoxyglucose differed in sensitivity to reversal by cAMP. The difference between the two repressions could be due to the fact that glucose-6-phosphate inhibited severely the accumulation of exogenous [3-H]cAMP by the membrane fraction, whereas 2-deoxyglucose had little effect on the accumulation of the nucleotide. On the other hand, a quick decrease in the level of [3-H]cAMP preaccumulated in the membrane fraction resulted from addition of either glucose-6-phosphate or 2-deoxyglucose. Results reported here suggest that repression of beta-galactosidase synthesis is associated with anabrupt decrease in cAMP levels at the intramembranal sites where beta-galactosidase is synthesized, and the major, if not sole, mechanism which leads to instantaneous drop of cAMP level is via the release of cAMP, but not by degradation of the nucleotide since the membrane fraction retained less than 10 percent of cellular cyclic phosphodiesterase and the activity of the enzyme was not affected by repressing sugars."} {"id": "PMID:165174", "title": "Mutants of Neurospora deficient in nicotinamide adenine dinucleotide (phosphate) glycohydrolase.", "content": "A new screening technique has been developed for the rapid identification of Neurospora crassa mutants that are deficient in nicotinamide adenine dinucleotide glycohydrolase (NADase) and nicotinamide adenine dinucleotide phosphate glycohydrolase (NADPase) activities. Using this procedure, five single-gene mutants were isolated whose singular difference from wild type appeared to be the absence of NAD(P)ase (EC 3.2.2.6). All five mutants were found to be genetically allelic and did not complement in heterocaryons. This gene, nada [NAD(P)ase], was localized in linkage group IV. One of the nada alleles was found to specify an enzyme that was critically temperature sensitive and had altered substrate affinity. Mutations at the nada locus did not affect the genetic program for the expression of NAD(P)ase during cell differentiation, nor did they have a general effect on NAD catabolism. Nada mutations did not have simultaneous effects on other glycohydrolase activities. Tests of dominance (in heterocaryons) and in vitro mixing experiments did not provide evidence that nada mutations alter activators or inhibitors of NAD(P)ase. Thus, the nada gene appears to specify only the structure of N. crassa NAD(P)ase.", "contents": "Mutants of Neurospora deficient in nicotinamide adenine dinucleotide (phosphate) glycohydrolase. A new screening technique has been developed for the rapid identification of Neurospora crassa mutants that are deficient in nicotinamide adenine dinucleotide glycohydrolase (NADase) and nicotinamide adenine dinucleotide phosphate glycohydrolase (NADPase) activities. Using this procedure, five single-gene mutants were isolated whose singular difference from wild type appeared to be the absence of NAD(P)ase (EC 3.2.2.6). All five mutants were found to be genetically allelic and did not complement in heterocaryons. This gene, nada [NAD(P)ase], was localized in linkage group IV. One of the nada alleles was found to specify an enzyme that was critically temperature sensitive and had altered substrate affinity. Mutations at the nada locus did not affect the genetic program for the expression of NAD(P)ase during cell differentiation, nor did they have a general effect on NAD catabolism. Nada mutations did not have simultaneous effects on other glycohydrolase activities. Tests of dominance (in heterocaryons) and in vitro mixing experiments did not provide evidence that nada mutations alter activators or inhibitors of NAD(P)ase. Thus, the nada gene appears to specify only the structure of N. crassa NAD(P)ase."} {"id": "PMID:165175", "title": "Denaturation and proteolytic digestion of porcine low-density lipoprotein in aqueous guanidine hydrochloride solutions.", "content": "The denaturation of porcine low-density lipoprotein (LDL) in aqueous guanidine hydrochloride (GuHCl) was studied by flotation velocity experiments, optical rotatory dispersion and fluorescence spectroscopy. The denaturation of LDL occurred between 2 and 4M GuGCl, where small sigmoidal changes in iptical rotation and fluorescence intensity were noted. The hydrated density of the native LDL was 1.036g/cm-3 and this remained constant upon denaturation in 4M GuHCl. The slope of the flotation coefficient-solvent density curve was 35 per cent less for denatured LDL than for the native LDL. Since there is no indication of splitting of LDL in 4M GuHCl, it is natural to interpret the result in terms of an increase of the translational frictional coefficient by 50 per cent. The observed changes in optical rotation, fluorescence intensity and flotation coefficient in 4M GuHCl were readily reversed and native LDL was recovered after removal of GuHCl by dialysis. Proteolytic treatment of denatured LDL produced digested LDL which had a hydrated density of 1.021g/cm-3 corresponding to the loss of 30 per cent of apo-LDL. The digested LDL behaved like a compact, globular particle in aqueous NaCl solution and in 4M GuHCl. These results can best be interpreted by a model of the LDL particle in which approximately 30 per cent of apo-LDL is exposed to the solvent, such that it can be reversibly denatured by GuHCl and at the same time is easily avalable to proteolytic enzymes, whereas the rest of apo-LDL is tightly associated with lipids and possibly buried inside the lipid moiety. SDS-polyacrylamide gel electrophoresis of the digested LDL revealed four major peptide fragments with sizes ranging from 70,000 to 100,000 daltons. We believe that the method and results described in this paper will have meaningful applications in the study of membrane proteins.", "contents": "Denaturation and proteolytic digestion of porcine low-density lipoprotein in aqueous guanidine hydrochloride solutions. The denaturation of porcine low-density lipoprotein (LDL) in aqueous guanidine hydrochloride (GuHCl) was studied by flotation velocity experiments, optical rotatory dispersion and fluorescence spectroscopy. The denaturation of LDL occurred between 2 and 4M GuGCl, where small sigmoidal changes in iptical rotation and fluorescence intensity were noted. The hydrated density of the native LDL was 1.036g/cm-3 and this remained constant upon denaturation in 4M GuHCl. The slope of the flotation coefficient-solvent density curve was 35 per cent less for denatured LDL than for the native LDL. Since there is no indication of splitting of LDL in 4M GuHCl, it is natural to interpret the result in terms of an increase of the translational frictional coefficient by 50 per cent. The observed changes in optical rotation, fluorescence intensity and flotation coefficient in 4M GuHCl were readily reversed and native LDL was recovered after removal of GuHCl by dialysis. Proteolytic treatment of denatured LDL produced digested LDL which had a hydrated density of 1.021g/cm-3 corresponding to the loss of 30 per cent of apo-LDL. The digested LDL behaved like a compact, globular particle in aqueous NaCl solution and in 4M GuHCl. These results can best be interpreted by a model of the LDL particle in which approximately 30 per cent of apo-LDL is exposed to the solvent, such that it can be reversibly denatured by GuHCl and at the same time is easily avalable to proteolytic enzymes, whereas the rest of apo-LDL is tightly associated with lipids and possibly buried inside the lipid moiety. SDS-polyacrylamide gel electrophoresis of the digested LDL revealed four major peptide fragments with sizes ranging from 70,000 to 100,000 daltons. We believe that the method and results described in this paper will have meaningful applications in the study of membrane proteins."} {"id": "PMID:165176", "title": "Mechanism of the ribosome-dependent uncoupled GTPase reaction catalyzed by polypeptide chain elongation factor G.", "content": "At low NH4-+ concentrations, 50S ribosomal subunits from E. coli were fully active in the absence of 30S ribosomal subunits, in forming a complex with the polypeptide chain elongation factor G (EF-G) and guanine nucleotide (ternary complex formation), and also in supporting EF-G dependent hydrolysis of GTP (uncoupled GTPase reaction). However, both activities were markedly inhibited on increasing the concentration of the monovalent cation, and at 160 mM NH4-+, the optimal concentration for polypeptide synthesis in a cell-free system, almost no activity was observed with 50S ribosomes alone. It was found that the inhibitory effect of NH4-+ was reversed by addition of 30S subunits. Thus, at 160 mM NH4-+, only 70S ribosomes were active in supporting the above two EF-G dependent reactions, whereas at 20 mM NH4-+, 50S ribosomes were almost as active as 70S ribosomes. Kinetic studies on inhibition by NH4-+ of the formation of 50S ribosome-EF-G-guanine nucleotide complex, indicated that the inhibition was due to reduction in the number of active 50S ribosomes which were capable of interacting with EF-G and GTP at higher concentrations of NH4-+. The inhibitory effects of NH4-+ on ternary complex formation and the uncoupled GTPase reaction were markedly influenced by temperature, and were much greater at 0 degrees than at 30 degrees. A conformational change of 50S subunits through association with 30S subunits is suggested.", "contents": "Mechanism of the ribosome-dependent uncoupled GTPase reaction catalyzed by polypeptide chain elongation factor G. At low NH4-+ concentrations, 50S ribosomal subunits from E. coli were fully active in the absence of 30S ribosomal subunits, in forming a complex with the polypeptide chain elongation factor G (EF-G) and guanine nucleotide (ternary complex formation), and also in supporting EF-G dependent hydrolysis of GTP (uncoupled GTPase reaction). However, both activities were markedly inhibited on increasing the concentration of the monovalent cation, and at 160 mM NH4-+, the optimal concentration for polypeptide synthesis in a cell-free system, almost no activity was observed with 50S ribosomes alone. It was found that the inhibitory effect of NH4-+ was reversed by addition of 30S subunits. Thus, at 160 mM NH4-+, only 70S ribosomes were active in supporting the above two EF-G dependent reactions, whereas at 20 mM NH4-+, 50S ribosomes were almost as active as 70S ribosomes. Kinetic studies on inhibition by NH4-+ of the formation of 50S ribosome-EF-G-guanine nucleotide complex, indicated that the inhibition was due to reduction in the number of active 50S ribosomes which were capable of interacting with EF-G and GTP at higher concentrations of NH4-+. The inhibitory effects of NH4-+ on ternary complex formation and the uncoupled GTPase reaction were markedly influenced by temperature, and were much greater at 0 degrees than at 30 degrees. A conformational change of 50S subunits through association with 30S subunits is suggested."} {"id": "PMID:165177", "title": "Hydrophobic interactions of the apo-Gln-I polypeptide component of human high density serum lipoprotein.", "content": "Apo-Gln-I, the major polypeptide component of human serum high density lipoprotein, has four noninteracting hydrophobic sites which associate with alkanes, anionic detergents, and cationic detergents. Hexane and octane bind to these sites with association constants of 6.8 times 10-2 and 1.8 times 10-4 liters/mol, respectively, and compete with the anionic detergent, sodium dodecyl sulfate (C12OSO3-minus), at low detergent ligand binding ratios (i.e. smaller than or equal to 1.0 mol of C12OSO3-minus per mol of protein). At higher detergent binding ratios (larger than 2 mol of C12OSO3-minus per mol of protein) the polypeptide cooperatively binds alkanes and a conformational change is induced.", "contents": "Hydrophobic interactions of the apo-Gln-I polypeptide component of human high density serum lipoprotein. Apo-Gln-I, the major polypeptide component of human serum high density lipoprotein, has four noninteracting hydrophobic sites which associate with alkanes, anionic detergents, and cationic detergents. Hexane and octane bind to these sites with association constants of 6.8 times 10-2 and 1.8 times 10-4 liters/mol, respectively, and compete with the anionic detergent, sodium dodecyl sulfate (C12OSO3-minus), at low detergent ligand binding ratios (i.e. smaller than or equal to 1.0 mol of C12OSO3-minus per mol of protein). At higher detergent binding ratios (larger than 2 mol of C12OSO3-minus per mol of protein) the polypeptide cooperatively binds alkanes and a conformational change is induced."} {"id": "PMID:165178", "title": "Cyclic adenosine 3':5'-monophosphate and the induction of deoxyribonucleic acid synthesis in liver.", "content": "A mixture containing glucagon and thyroid hormone was previously devised that enhances markedly nuclear DNA replication and mitosis in the parenchymal liver cells of the unoperated rat. It is now shown that the glucagon of the stimulatory solution can be completely replaced by a mixture of a butyryl derivative of cyclic adenosine 3':5'-monophosphate and theophylline. Cyclic guanosine 3':5'-monophosphate and its butyryl derivatives and insulin and high levels of glucose are inactive. The inactivity of N2-monobutyryl cyclic guanosine 3':5'-monophosphate cannot be ascribed to rapid breakdown in the animal or to the impenetrability of the liver cell since the coumpound elevates the rate of hepatic amino acid transport and the activity of ornithine decarboxylase. The observation of others (MacManus, J.P., Franks, D.J., Youdale, T. & Braceland, B.M. (1972) Biochem. Biophys. Res. Commun. 49, 1201-1207) that the level of cylcic adenosine 3':5'-monophosphate is raised during most of the prereplicative period after 70% hepatectomy is confirmed. The evidence supports a positive role for adenosine 3':5-monophosphate in regulating DNA synthesis in the liver.", "contents": "Cyclic adenosine 3':5'-monophosphate and the induction of deoxyribonucleic acid synthesis in liver. A mixture containing glucagon and thyroid hormone was previously devised that enhances markedly nuclear DNA replication and mitosis in the parenchymal liver cells of the unoperated rat. It is now shown that the glucagon of the stimulatory solution can be completely replaced by a mixture of a butyryl derivative of cyclic adenosine 3':5'-monophosphate and theophylline. Cyclic guanosine 3':5'-monophosphate and its butyryl derivatives and insulin and high levels of glucose are inactive. The inactivity of N2-monobutyryl cyclic guanosine 3':5'-monophosphate cannot be ascribed to rapid breakdown in the animal or to the impenetrability of the liver cell since the coumpound elevates the rate of hepatic amino acid transport and the activity of ornithine decarboxylase. The observation of others (MacManus, J.P., Franks, D.J., Youdale, T. & Braceland, B.M. (1972) Biochem. Biophys. Res. Commun. 49, 1201-1207) that the level of cylcic adenosine 3':5'-monophosphate is raised during most of the prereplicative period after 70% hepatectomy is confirmed. The evidence supports a positive role for adenosine 3':5-monophosphate in regulating DNA synthesis in the liver."} {"id": "PMID:165179", "title": "Differentiation between binding and transport of dansylgalactosides in Escherichia coli.", "content": "The results presented in this paper confirm and extend previous observations which indicate that fluorescent dansylgalactsodes bind to the beta-galactoside carrier protein but do not penetrate the cytoplasmic membrane. The conclusion is supported by the following observations. (a) Although 2'-(N-dansyl)aminoethyl-beta-D-thiogalactopyranoside and 2'-(N-dansyl)aminoethyl-beta-D-galactopyranoside are competitive inhibitors of lactose transport in intact cells of Escherichia coli and induce the in vitro synthesis of beta-galactosidase, they do not induce beta-galactosidase in vivo. (b) p-Chloromercuribenzenesulfonate does not cause efflux of lactose from the intravesicular pool, but causes rapid reversal of D-lactate-induced dansylgalactoside fluorescence. (c) Dansylgalactosides inhibit dilution-induced, carrier-mediated lactose efflux.", "contents": "Differentiation between binding and transport of dansylgalactosides in Escherichia coli. The results presented in this paper confirm and extend previous observations which indicate that fluorescent dansylgalactsodes bind to the beta-galactoside carrier protein but do not penetrate the cytoplasmic membrane. The conclusion is supported by the following observations. (a) Although 2'-(N-dansyl)aminoethyl-beta-D-thiogalactopyranoside and 2'-(N-dansyl)aminoethyl-beta-D-galactopyranoside are competitive inhibitors of lactose transport in intact cells of Escherichia coli and induce the in vitro synthesis of beta-galactosidase, they do not induce beta-galactosidase in vivo. (b) p-Chloromercuribenzenesulfonate does not cause efflux of lactose from the intravesicular pool, but causes rapid reversal of D-lactate-induced dansylgalactoside fluorescence. (c) Dansylgalactosides inhibit dilution-induced, carrier-mediated lactose efflux."} {"id": "PMID:165180", "title": "Deoxyribinucleic acid-binding proteins in virus-transformed cell lines.", "content": "The synthesis of proteins with affinity for DNA has been studied in clones of a Syrian hamster cell line (NIL) and subclones of this line transformed by polyoma virus (NIL-Py) or hamster sarcoma virus (NIL-HSV). The results show that the synthesis of DNA-binding proteins in NIL and in its virus-transformed derivatives NIL-Py and NIL-HSV is very similar in exponentially growing cells, but in dense culture there is a very significant difference in the level of a protein (P8), which is much higher in the transformed lines than in untransformed NIL. The high levels of P8 in dense transformed cells have been observed in all the clones of transformed cells examined, indicating that this behavior of P8 is related to transformation and not simply due to a fortuitous clonal selection from the NIL. Experiments with synchronized cells indicate that the time of maximal P8 synthesis relative to cellular DNA synthesis in NIL-HSV precedes that observed in NIL cells. P8 has a molecular weight of 30,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and is present in large amounts in the transformed cells in dense culture, where it makes up 0.5 to 1% of the total soluble protein.", "contents": "Deoxyribinucleic acid-binding proteins in virus-transformed cell lines. The synthesis of proteins with affinity for DNA has been studied in clones of a Syrian hamster cell line (NIL) and subclones of this line transformed by polyoma virus (NIL-Py) or hamster sarcoma virus (NIL-HSV). The results show that the synthesis of DNA-binding proteins in NIL and in its virus-transformed derivatives NIL-Py and NIL-HSV is very similar in exponentially growing cells, but in dense culture there is a very significant difference in the level of a protein (P8), which is much higher in the transformed lines than in untransformed NIL. The high levels of P8 in dense transformed cells have been observed in all the clones of transformed cells examined, indicating that this behavior of P8 is related to transformation and not simply due to a fortuitous clonal selection from the NIL. Experiments with synchronized cells indicate that the time of maximal P8 synthesis relative to cellular DNA synthesis in NIL-HSV precedes that observed in NIL cells. P8 has a molecular weight of 30,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and is present in large amounts in the transformed cells in dense culture, where it makes up 0.5 to 1% of the total soluble protein."} {"id": "PMID:165181", "title": "Uncoupling and specific inhibition of phosphoryl transfer reactions in mitochondria by antibiotic A20668.", "content": "A20668 A, B, and C are polypeptide antibiotics that inhibit phosphorylation of ADP, Mg2t-ATPase, and the ATP-driven transhydrogenase of rat liver submitochondrial particles, but not the purified F1 ATPase. In intact mitochondria, 120668 inhibits uncoupler-induced ATPase, State 3 respiration, and phosphorylation; the A and B forms are approximately equipotent with rutamycin, whereas A20668 C is less effective. Concentrations of A20668 slightly greater than required for complete inhibition of phosphoryl transfer stimulate rapid, uncoupled respiration by mitochondria under State 3 of 4 conditions. A20668 A and B are more effective uncouplers than A20668 C. In the presence of venturicidin or ossamycin, concentrations of A20668, which alone do not uncouple, stimulate oxygen consumption of mitochondria incubated under either State 3 of 4 conditions. A20668 uncoupling is not potentiated by prior inhibition of phosphoryl transfer by venturicidin X, rutamycin, aurovertin, or efrapeptin. A20668 increases mitochondrial permeability to protons in passive swelling experiments where facilitation of proton conductance correlates well with potency to uncouple. A20668 apparently binds initially at a unique locus to inhibit mitochondrial phosphoryl transfer reactions. When this site is saturated, additional antibiotic may uncouple by increasing proton conductance of mitochondria. Binding of venturicidin or ossamycin appears to interfere with the binding of A20668 to its adjacent inhibitory site, thus effectively increasing the concentration of A20668 available to uncouple.", "contents": "Uncoupling and specific inhibition of phosphoryl transfer reactions in mitochondria by antibiotic A20668. A20668 A, B, and C are polypeptide antibiotics that inhibit phosphorylation of ADP, Mg2t-ATPase, and the ATP-driven transhydrogenase of rat liver submitochondrial particles, but not the purified F1 ATPase. In intact mitochondria, 120668 inhibits uncoupler-induced ATPase, State 3 respiration, and phosphorylation; the A and B forms are approximately equipotent with rutamycin, whereas A20668 C is less effective. Concentrations of A20668 slightly greater than required for complete inhibition of phosphoryl transfer stimulate rapid, uncoupled respiration by mitochondria under State 3 of 4 conditions. A20668 A and B are more effective uncouplers than A20668 C. In the presence of venturicidin or ossamycin, concentrations of A20668, which alone do not uncouple, stimulate oxygen consumption of mitochondria incubated under either State 3 of 4 conditions. A20668 uncoupling is not potentiated by prior inhibition of phosphoryl transfer by venturicidin X, rutamycin, aurovertin, or efrapeptin. A20668 increases mitochondrial permeability to protons in passive swelling experiments where facilitation of proton conductance correlates well with potency to uncouple. A20668 apparently binds initially at a unique locus to inhibit mitochondrial phosphoryl transfer reactions. When this site is saturated, additional antibiotic may uncouple by increasing proton conductance of mitochondria. Binding of venturicidin or ossamycin appears to interfere with the binding of A20668 to its adjacent inhibitory site, thus effectively increasing the concentration of A20668 available to uncouple."} {"id": "PMID:165182", "title": "Deoxythymidine 3', 5'-di-p-nitrophenyl phosphate as a synthetic substrate for bovine pancreatic deoxyribonuclease.", "content": "Bovine pancreatic deoxyribonuclease liberates p-nitrophenol from the 3'-group of deoxythymidine 3', 5'-di-p-nitrophenyl phosphate. A similar hydrolysis occurs with deoxythymidine 3'-p-nitrophenyl phosphate 5'-phsophate, but the rate is less than 2% of that with the di-p-nitrophenyl ester. The rate of formation of the p-nitrophenol, measured spectrophotometrically at 400 nm, varies linearly with DNase concentration. The binding of the substrate is not strong (K-m(app) in the 10 mM range), but the hydrolysis is rapid; 1 mug of DNase (free from other phosphodiesterases) can be assayed in 3 min after addition to a 10 mM substrate solution at pH 7.2, 10mM in MnCl2, and 1mM in CaCl2. All four bovine pancreatic DNases (A,B,C, and D) show the same relative activities toward DNA and toward the di-p-nitrophenyl ester; both activities are lost when DNase is inactivated by iodoacetate or by trypsin. The specificity of DNase toward the di-p-nitrophenyl substrate is different from that which has been established for the enzyme's predominant action on DNA or synthetic oligonucleotides, where a monoesterified phosphate group is formed at the 5'-position.", "contents": "Deoxythymidine 3', 5'-di-p-nitrophenyl phosphate as a synthetic substrate for bovine pancreatic deoxyribonuclease. Bovine pancreatic deoxyribonuclease liberates p-nitrophenol from the 3'-group of deoxythymidine 3', 5'-di-p-nitrophenyl phosphate. A similar hydrolysis occurs with deoxythymidine 3'-p-nitrophenyl phosphate 5'-phsophate, but the rate is less than 2% of that with the di-p-nitrophenyl ester. The rate of formation of the p-nitrophenol, measured spectrophotometrically at 400 nm, varies linearly with DNase concentration. The binding of the substrate is not strong (K-m(app) in the 10 mM range), but the hydrolysis is rapid; 1 mug of DNase (free from other phosphodiesterases) can be assayed in 3 min after addition to a 10 mM substrate solution at pH 7.2, 10mM in MnCl2, and 1mM in CaCl2. All four bovine pancreatic DNases (A,B,C, and D) show the same relative activities toward DNA and toward the di-p-nitrophenyl ester; both activities are lost when DNase is inactivated by iodoacetate or by trypsin. The specificity of DNase toward the di-p-nitrophenyl substrate is different from that which has been established for the enzyme's predominant action on DNA or synthetic oligonucleotides, where a monoesterified phosphate group is formed at the 5'-position."} {"id": "PMID:165183", "title": "Glycerol as an agent eliciting small conformational changes in alcohol dehydrogenase.", "content": "Yeast alcohol dehydrogenase is an example of a protein in which the K-m for substrate is substantially decreased by the presence of glycerol. The polyol has the effect at pH 8.0 or above of decreasing K-m and K-s for substrate and of altering both the protein's intrinsic fluorescence and ultraviolet absorption difference spectrum. The relationship between each of thse parameters and glycerol concentration displays a transition at a glycerol concentration of 20%. Circular dichroism values for the enzyme are not affected by glycerol over a large range of concentration and temperature. Treatment of the enzyme with glutaraldehyde results in the formation of cross-linked tetramers, the K-m of which are not altered by the presence of the solvent. The data are interpreted as reflecting a change in the conformation of the protein induced by glycerol.", "contents": "Glycerol as an agent eliciting small conformational changes in alcohol dehydrogenase. Yeast alcohol dehydrogenase is an example of a protein in which the K-m for substrate is substantially decreased by the presence of glycerol. The polyol has the effect at pH 8.0 or above of decreasing K-m and K-s for substrate and of altering both the protein's intrinsic fluorescence and ultraviolet absorption difference spectrum. The relationship between each of thse parameters and glycerol concentration displays a transition at a glycerol concentration of 20%. Circular dichroism values for the enzyme are not affected by glycerol over a large range of concentration and temperature. Treatment of the enzyme with glutaraldehyde results in the formation of cross-linked tetramers, the K-m of which are not altered by the presence of the solvent. The data are interpreted as reflecting a change in the conformation of the protein induced by glycerol."} {"id": "PMID:165184", "title": "Human chorionic gonadotropin. V. Tissue specificity of binding and partial characterization of soluble human chorionic gonadotropin-receptor complexes.", "content": "An in vivo human chorionic gonadotropin (hCG)-receptor complex was solubilized from the subcellular fraction of ovarian and testicular tissues of rats that had been injected with 125-I-labeled hCG. The soluble hCG-receptor complex was partially characterized by Sepharose 6B chromatography in the presence of the nonionic detergent, Emulphogene, and was shown to have a molecular size of about 65 A. By this method it was also shown that the in vivo uptake of radioactivity by rat gonadal tissues represents 125-I-hCG and not the dissociated subunits or degradation products of the hormone. A soluble hCG-receptor complex isolated in vitro in approximately the same yield from both rat testicular and ovarian homogenates was shown to be the same size. The hCG-receptor appears to be specifically located in gonadal tissue; a corresponding hCG-receptor complex was not obtained from liver or kidney that incorporated significant levels of 125-I-hCG administered in vivo. Furthermore, a desialyzed hCG-receptor complex was obtained from rat testis but not liver; desialyzed hCG, like other desialyzed glycoproteins, is nonspecifically bound by rat liver homogenates. The binding of hCG and luteinizing hormone (LH) by rat testis receptor exhibits a high degree of specificity. Other glycoprotein hormones without LH activity, such as follicle-stimulating hormone and thyroid-stimulating hormone, and glycoproteins such as fetuin or alpha1-acid glycoprotein do not bind to the hCG/LH receptors. Desialyzed hCG was 2 times more effective in competing for binding to rat testis receptors than \"native\" hCG, indicating that caution must be exercised when the radioligand receptor assay is utilized to assay hCG preparations varying in sialic acid content.", "contents": "Human chorionic gonadotropin. V. Tissue specificity of binding and partial characterization of soluble human chorionic gonadotropin-receptor complexes. An in vivo human chorionic gonadotropin (hCG)-receptor complex was solubilized from the subcellular fraction of ovarian and testicular tissues of rats that had been injected with 125-I-labeled hCG. The soluble hCG-receptor complex was partially characterized by Sepharose 6B chromatography in the presence of the nonionic detergent, Emulphogene, and was shown to have a molecular size of about 65 A. By this method it was also shown that the in vivo uptake of radioactivity by rat gonadal tissues represents 125-I-hCG and not the dissociated subunits or degradation products of the hormone. A soluble hCG-receptor complex isolated in vitro in approximately the same yield from both rat testicular and ovarian homogenates was shown to be the same size. The hCG-receptor appears to be specifically located in gonadal tissue; a corresponding hCG-receptor complex was not obtained from liver or kidney that incorporated significant levels of 125-I-hCG administered in vivo. Furthermore, a desialyzed hCG-receptor complex was obtained from rat testis but not liver; desialyzed hCG, like other desialyzed glycoproteins, is nonspecifically bound by rat liver homogenates. The binding of hCG and luteinizing hormone (LH) by rat testis receptor exhibits a high degree of specificity. Other glycoprotein hormones without LH activity, such as follicle-stimulating hormone and thyroid-stimulating hormone, and glycoproteins such as fetuin or alpha1-acid glycoprotein do not bind to the hCG/LH receptors. Desialyzed hCG was 2 times more effective in competing for binding to rat testis receptors than \"native\" hCG, indicating that caution must be exercised when the radioligand receptor assay is utilized to assay hCG preparations varying in sialic acid content."} {"id": "PMID:165185", "title": "Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake.", "content": "Receptors for insulin and epidermal growth factor (EGF) have been studied in confluent cultured intact human fibroblast monolayers. 125-I-EGF binds specifically to fibroblast monolayers. Half-maximal binding is observed at 4 times 10 minus 10 M EGF; at saturation of binding approximately 4 times 10-4 molecules of EGF are bound per cell. 125-I-Insulin is also bound specifically by intact monolayers with half-maximal binding observed at 10 minus 9 M insulin; about 4 times 10-3 molecules of insulin are bound per cell at saturation. Both insulin and EGF stimulate thymidine incorporation and alpha-aminoisobutyrate uptake. A half-maximal effect for insulin is observed at about 10 minus 9 M, both for the stimulation of thymidine incorporation and for the stimulation of alpha-aminoisobutyrate uptake; for EGF, half-maximal stimulation of both thymidine incorporation and alpha-aminoisobutyrate uptake is observed at 10 minus 10 M EGF. EGF causes an apparent greater stimulation of thymidine incorporation than does insulin, whereas the stimulation of alpha-aminoisobutyrate uptake is the same for both insulin and EGF. The degree of stimulation of alpha-aminoisobutyrate uptake by either insulin or EGF varied (1.2- to 2-fold) from one batch of cells to another, as did the measured values of the apparent K-m (average value 1 mM, range 0.6 to 2 mM) and V-max (average, 0.82, range 0.78 to 0.87 nmol/100 mug of protein per min) for alpha-aminoisobutyrate. Nonetheless, the apparent K-m of each peptide for stimulation of alpha-aminoisobutyrate uptake was independent of the degree of increase in alpha-aminoisobutyrate uptake, and was constant from one batch of cells to another. The peptide-mediated stimulation of alpha-aminoisobutyrate uptake can be attributed to a decrease in the apparent K-m for alpha-aminoisobutyrate (e.g. for insulin) from 0.70 to 0.57 mM; for EGF from 0.87 to 0.66 mM) and a concomitant increase in the apparent V-max for alpha-aminoisobutyrate (e.g. for insulin from 0.78 to 0.87 and for EGF from 0.80 to 0.84 nmol/min/100 mug of cell protein). The stimulation requires a 40- to 60-min period of preincubation with either peptide and is blocked by pretreating cells with cycloheximide. In the presence of ouabain, both peptides inhibit rather than stimulate alpha-aminoisobutyrate uptake; ouabain lowers the basal rate of alpha-aminoisobutyrate uptake. The uptake of 3-0-methyl-D-glucose is not affected by either EGF or insulin under conditions where insulin stimulates fat cell transport. These observations indicate that cultured human fibroblasts possess specific binding sites for insulin and EGF, which sites can be related to two actions of the peptides: stimulation of thymidine incorporation and alpha-aminoisobutyrate uptake.", "contents": "Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake. Receptors for insulin and epidermal growth factor (EGF) have been studied in confluent cultured intact human fibroblast monolayers. 125-I-EGF binds specifically to fibroblast monolayers. Half-maximal binding is observed at 4 times 10 minus 10 M EGF; at saturation of binding approximately 4 times 10-4 molecules of EGF are bound per cell. 125-I-Insulin is also bound specifically by intact monolayers with half-maximal binding observed at 10 minus 9 M insulin; about 4 times 10-3 molecules of insulin are bound per cell at saturation. Both insulin and EGF stimulate thymidine incorporation and alpha-aminoisobutyrate uptake. A half-maximal effect for insulin is observed at about 10 minus 9 M, both for the stimulation of thymidine incorporation and for the stimulation of alpha-aminoisobutyrate uptake; for EGF, half-maximal stimulation of both thymidine incorporation and alpha-aminoisobutyrate uptake is observed at 10 minus 10 M EGF. EGF causes an apparent greater stimulation of thymidine incorporation than does insulin, whereas the stimulation of alpha-aminoisobutyrate uptake is the same for both insulin and EGF. The degree of stimulation of alpha-aminoisobutyrate uptake by either insulin or EGF varied (1.2- to 2-fold) from one batch of cells to another, as did the measured values of the apparent K-m (average value 1 mM, range 0.6 to 2 mM) and V-max (average, 0.82, range 0.78 to 0.87 nmol/100 mug of protein per min) for alpha-aminoisobutyrate. Nonetheless, the apparent K-m of each peptide for stimulation of alpha-aminoisobutyrate uptake was independent of the degree of increase in alpha-aminoisobutyrate uptake, and was constant from one batch of cells to another. The peptide-mediated stimulation of alpha-aminoisobutyrate uptake can be attributed to a decrease in the apparent K-m for alpha-aminoisobutyrate (e.g. for insulin) from 0.70 to 0.57 mM; for EGF from 0.87 to 0.66 mM) and a concomitant increase in the apparent V-max for alpha-aminoisobutyrate (e.g. for insulin from 0.78 to 0.87 and for EGF from 0.80 to 0.84 nmol/min/100 mug of cell protein). The stimulation requires a 40- to 60-min period of preincubation with either peptide and is blocked by pretreating cells with cycloheximide. In the presence of ouabain, both peptides inhibit rather than stimulate alpha-aminoisobutyrate uptake; ouabain lowers the basal rate of alpha-aminoisobutyrate uptake. The uptake of 3-0-methyl-D-glucose is not affected by either EGF or insulin under conditions where insulin stimulates fat cell transport. These observations indicate that cultured human fibroblasts possess specific binding sites for insulin and EGF, which sites can be related to two actions of the peptides: stimulation of thymidine incorporation and alpha-aminoisobutyrate uptake."} {"id": "PMID:165186", "title": "Kinetic demonstration of the intermediate role of aminoacyl-adenylate-enzyme in the formation of valyl transfer ribonucleic acid.", "content": "The question whether aminoacyl-tRNA synthetases act in a stepwise or in a concerted mechanism has been investigated kinetically with the valine enzyme of Escherichia coli, which had been used in previous studies by others who concluded that the physiological mechanism is concerted. An exchange between aminoacyl-tRNA and tRNA, dependent upon AMP, was studied. PP-i inhibits this exchange completely in the presence of Mg2+ and AMP but in the absence of added Mg2+ or with dAMP as the nucleotide the inhibition by PP-i is only partial; this is compatible with a stepwise, not a concerted, reaction. Exchange of isotopically labeled substrates in a system at chemical equilibrium also shows effects of substrate concentrations on rates in agreement with the predictions of a stepwise mechanism.", "contents": "Kinetic demonstration of the intermediate role of aminoacyl-adenylate-enzyme in the formation of valyl transfer ribonucleic acid. The question whether aminoacyl-tRNA synthetases act in a stepwise or in a concerted mechanism has been investigated kinetically with the valine enzyme of Escherichia coli, which had been used in previous studies by others who concluded that the physiological mechanism is concerted. An exchange between aminoacyl-tRNA and tRNA, dependent upon AMP, was studied. PP-i inhibits this exchange completely in the presence of Mg2+ and AMP but in the absence of added Mg2+ or with dAMP as the nucleotide the inhibition by PP-i is only partial; this is compatible with a stepwise, not a concerted, reaction. Exchange of isotopically labeled substrates in a system at chemical equilibrium also shows effects of substrate concentrations on rates in agreement with the predictions of a stepwise mechanism."} {"id": "PMID:165187", "title": "The role of polyamines in the aminoacyl transfer ribonucleic acid synthetase reactions. Demonstration of the requirement for magnesium ion and a secondary stimulatory effect of spermine.", "content": "Spermine and related polyamines have been reported to substitute for Mg2+ in the aminoacylation of tRNA catalyzed by aminoacyl-tRNA synthetases, but not in the ATP-PP-i exchange reaction. Such observations have led some workers to propose that these reactions proceed via a concerted mechanism rather than the usual two-step mechanism involving an aminoacyladenylate intermediate. In an attempt to elucidate the mechanism of the spermine effect on acylation and exchange, both reactions were re-examined using isoleucyl-tRNA synthetase from Escherichia coli. In the absence of added Mg2+ untreated tRNA was acylated in the presence of spermine, but tRNA from which Mg2+ had been scrupulously removed was not. ATP-PP-i exchange was not observed when spermine was used in place of Mg2+; however, if tRNA possessing sequestered Mg2+ was added, the exchange reaction was observed. These data suggest that a primary effect of spermine is to displace bound Mg2+ from tRNA in quantities sufficient to promote both the ATP-PP-i exchange and esterification of tRNA. The previously reported stimulatory effects of polyamines on these reactions are believed to be artifacts due to Mg2+ contamination of tRNA. Providing trace levels of Mg2+ are present, spermine exerts a secondary stimulation of the rate of aminoacylation, the mechanism of which is unknown. The results presented refute arguments that these enzymes proceed by a concerted mechansim and support the intermediacy of aminoacyladenylates.", "contents": "The role of polyamines in the aminoacyl transfer ribonucleic acid synthetase reactions. Demonstration of the requirement for magnesium ion and a secondary stimulatory effect of spermine. Spermine and related polyamines have been reported to substitute for Mg2+ in the aminoacylation of tRNA catalyzed by aminoacyl-tRNA synthetases, but not in the ATP-PP-i exchange reaction. Such observations have led some workers to propose that these reactions proceed via a concerted mechanism rather than the usual two-step mechanism involving an aminoacyladenylate intermediate. In an attempt to elucidate the mechanism of the spermine effect on acylation and exchange, both reactions were re-examined using isoleucyl-tRNA synthetase from Escherichia coli. In the absence of added Mg2+ untreated tRNA was acylated in the presence of spermine, but tRNA from which Mg2+ had been scrupulously removed was not. ATP-PP-i exchange was not observed when spermine was used in place of Mg2+; however, if tRNA possessing sequestered Mg2+ was added, the exchange reaction was observed. These data suggest that a primary effect of spermine is to displace bound Mg2+ from tRNA in quantities sufficient to promote both the ATP-PP-i exchange and esterification of tRNA. The previously reported stimulatory effects of polyamines on these reactions are believed to be artifacts due to Mg2+ contamination of tRNA. Providing trace levels of Mg2+ are present, spermine exerts a secondary stimulation of the rate of aminoacylation, the mechanism of which is unknown. The results presented refute arguments that these enzymes proceed by a concerted mechansim and support the intermediacy of aminoacyladenylates."} {"id": "PMID:165188", "title": "The primary nucleotide sequence of nuclear U-2 ribonucleic acid. The 5'-terminal portion of the molecule.", "content": "The nuclear U-2 RNA which is highly modified (Reddy, R., Ro Choi, T.S., Henning, D., Shibata, H., Choi, Y.C., and Busch H. (1972) J. Biol. Chem. 247, 7245-7250) contains 13 pseudouridylic acid residues, 10 2'-O-methylated nucleotides and two modified bases including N-2,2, 7-trimethyl guanylic acid in its 5'-terminal portion (69 nucleotides). With the determination of this sequence and its overlap with the 3' portion of the molecule (nucleotides 70 to 196), the over-all nucleotide sequence of this RNA is:(see article). The concentration of modified nucleotides in its 5' portion is greater than for any RNA sequenced thus far.", "contents": "The primary nucleotide sequence of nuclear U-2 ribonucleic acid. The 5'-terminal portion of the molecule. The nuclear U-2 RNA which is highly modified (Reddy, R., Ro Choi, T.S., Henning, D., Shibata, H., Choi, Y.C., and Busch H. (1972) J. Biol. Chem. 247, 7245-7250) contains 13 pseudouridylic acid residues, 10 2'-O-methylated nucleotides and two modified bases including N-2,2, 7-trimethyl guanylic acid in its 5'-terminal portion (69 nucleotides). With the determination of this sequence and its overlap with the 3' portion of the molecule (nucleotides 70 to 196), the over-all nucleotide sequence of this RNA is:(see article). The concentration of modified nucleotides in its 5' portion is greater than for any RNA sequenced thus far."} {"id": "PMID:165189", "title": "Nucleotide sequence of U-2 ribonucleic acid. The sequence of the 5'-terminal oligonucleotide.", "content": "The nucleotide sequences were determined for the 5'-oligonucleotides obtained by complete pancreatic RNase digestion (P25) and complete T1 RNase digestion (T27) of U-2 RNA. Complete digestion of oligonucleotide P25 with snake venom phosphodiesterase produced pm3 2,2,7G, pAm, pUm, and pCp in approximately equimolar ratios. Partial digestion of these oligonucleotides with snake venom phosphodiesterase produced -Um-C-Gp and pAm-Um, indicating the sequence of the 3'-terminal portion of the 5'-oligonucleotide is pAm-Um-C-Gp. The 5'-terminal oligonucleotide did not contain a 5'-phosphate and no free nucleoside was released from the 5' end by venom phosphodiesterase digestion. Since free pm3 2,2,7G was released by digestion with nucleotide pyrophosphatase and limited digestion with snake venom phosphodiesterase, this nucleotide is apparently linked to pAm in a pyrophosphate linkage. Mass spectrometry and thin layer chromatography in borate systems showed the ribose of m3 2, 2, 7G contains no 2'O-methyl residue. Moreover, the finding that the ribose of m3 2, 2, 7G was oxidized by NaIO4 and reduced by KB3H4 in intact U-2 RNA rules out other linkages involving the 2' and 3' positions. Accordingly, it is concluded that the structure of the 5'-terminal pentanucleotide of U-2 RNA is(see article).", "contents": "Nucleotide sequence of U-2 ribonucleic acid. The sequence of the 5'-terminal oligonucleotide. The nucleotide sequences were determined for the 5'-oligonucleotides obtained by complete pancreatic RNase digestion (P25) and complete T1 RNase digestion (T27) of U-2 RNA. Complete digestion of oligonucleotide P25 with snake venom phosphodiesterase produced pm3 2,2,7G, pAm, pUm, and pCp in approximately equimolar ratios. Partial digestion of these oligonucleotides with snake venom phosphodiesterase produced -Um-C-Gp and pAm-Um, indicating the sequence of the 3'-terminal portion of the 5'-oligonucleotide is pAm-Um-C-Gp. The 5'-terminal oligonucleotide did not contain a 5'-phosphate and no free nucleoside was released from the 5' end by venom phosphodiesterase digestion. Since free pm3 2,2,7G was released by digestion with nucleotide pyrophosphatase and limited digestion with snake venom phosphodiesterase, this nucleotide is apparently linked to pAm in a pyrophosphate linkage. Mass spectrometry and thin layer chromatography in borate systems showed the ribose of m3 2, 2, 7G contains no 2'O-methyl residue. Moreover, the finding that the ribose of m3 2, 2, 7G was oxidized by NaIO4 and reduced by KB3H4 in intact U-2 RNA rules out other linkages involving the 2' and 3' positions. Accordingly, it is concluded that the structure of the 5'-terminal pentanucleotide of U-2 RNA is(see article)."} {"id": "PMID:165190", "title": "A kinetic analysis of the estrogen receptor transformation.", "content": "The rate of the 4 to 5 S estrogen-binding protein (EBP) in vitro transformation was measured by sucrose gradient centrifugation analysis. The temperature-activated 4 to 5 S EBP transformation is found to be highly reproducible without loss of [3H]estradiol-binding activity in a buffer containing an excess of [3H]estradiol, 40 mM Tris, 1 mM dithiothreitol, and 1 M urea at pH 7.4. The presence of [3H]estradiol is necessary for the 4 to 5 EBP transformation. A kinetic analysis of the 4 to 5 EBP transformation shows that it is a bimolecular reaction, the dimerization of the 4 S EBP with a second (similar or dissimilar) monomer or subunit. In buffers containing 0.4 M KCl the apparent second order rate constant is 2.3 plus or minus 0-2 times 10-7 M minus 1 min minus 1 at 28 degrees. The reaction is independent of the initial receptor concentration, suggesting that the 4 S EBP is dissociated into monomeric units in buffers of high ionic strength. In buffers without KCl or with 0.1 M KCl the apparent second order rate constant of receptor transformation increases with decreasing receptor concentration. This suggests that the 4 S EBP is associated weakly with another macromolecule (or macromolecules) in buffers of low ionic strength. The rate of 4 to 5 S EBP transformation shows a 200-fold increase between 0 and 35 degrees. The Arrhenius energy of activation is 21.3 kcal mol minus 1 in buffer without KCl and 19.1 kcal mol minus 1 in buffer with 0.4 M KCl. Following the temperature-activated dimerization, the avidity of binding between the 4 S EBP and its complementary subunit is increased, 0.4 M KCl can no longer cause dissociation, and the 5 S EBP dimer appears. This kinetic analysis indicates that the avidity of binding between the subunits of the estrogen receptor is modulated by estradiol, temperature, and ionic strength. We propose that these interactions of the estrogen receptor's subunits reflect conformational changes involved in receptor activation.", "contents": "A kinetic analysis of the estrogen receptor transformation. The rate of the 4 to 5 S estrogen-binding protein (EBP) in vitro transformation was measured by sucrose gradient centrifugation analysis. The temperature-activated 4 to 5 S EBP transformation is found to be highly reproducible without loss of [3H]estradiol-binding activity in a buffer containing an excess of [3H]estradiol, 40 mM Tris, 1 mM dithiothreitol, and 1 M urea at pH 7.4. The presence of [3H]estradiol is necessary for the 4 to 5 EBP transformation. A kinetic analysis of the 4 to 5 EBP transformation shows that it is a bimolecular reaction, the dimerization of the 4 S EBP with a second (similar or dissimilar) monomer or subunit. In buffers containing 0.4 M KCl the apparent second order rate constant is 2.3 plus or minus 0-2 times 10-7 M minus 1 min minus 1 at 28 degrees. The reaction is independent of the initial receptor concentration, suggesting that the 4 S EBP is dissociated into monomeric units in buffers of high ionic strength. In buffers without KCl or with 0.1 M KCl the apparent second order rate constant of receptor transformation increases with decreasing receptor concentration. This suggests that the 4 S EBP is associated weakly with another macromolecule (or macromolecules) in buffers of low ionic strength. The rate of 4 to 5 S EBP transformation shows a 200-fold increase between 0 and 35 degrees. The Arrhenius energy of activation is 21.3 kcal mol minus 1 in buffer without KCl and 19.1 kcal mol minus 1 in buffer with 0.4 M KCl. Following the temperature-activated dimerization, the avidity of binding between the 4 S EBP and its complementary subunit is increased, 0.4 M KCl can no longer cause dissociation, and the 5 S EBP dimer appears. This kinetic analysis indicates that the avidity of binding between the subunits of the estrogen receptor is modulated by estradiol, temperature, and ionic strength. We propose that these interactions of the estrogen receptor's subunits reflect conformational changes involved in receptor activation."} {"id": "PMID:165191", "title": "Cytochrome synthesis in synchronous cultures of the yeast, Saccharomyces cerevisiae.", "content": "The synthesis of cytochromes aa3, b, and c has been investigated during synchronous growth in the yeast, Saccharomyces cerevisiae. These cytochromes increase in concentration continuously throughout each cell cycle, with an approximate doubling in rate during successive cycles. The rates of cytochrome formation are considerably higher in galactose-grown cultures than in cells grown in glucose. Although cytochrome aa3 increases at a continuous rate, its functional counterpart, cytochrome c oxidase, increases in stepwise fashion, with the increments occurring at the beginning of each new cell cycle. Chloramphenicol, a specific inhibitor of intramitochondrial protein synthesis, inhibits the formation of cytochrome aa3 at all stages of the cell cycle, but does not inhibit cytochrome c. Chloramphenicol exhibits a somewhat intermediate effect on cytochrome b synthesis, with transient inhibition occurring only when the drug is added prior to or during the initial part of the first cell cycle. After this time, chloramphenicol had no effect on the rate of cytochrome b synthesis. The data indicate that under our conditions of cell synchrony mitochondrial membrane formation as reflected by increments in mitochondrial cytochromes occurs by continuous accretion of new material throughout the cell cycle. Intramitochondrially synthesized polypeptide products, responsible for the formation of new cytochrome aa3, appear to be synthesized throughout the cell cycle.", "contents": "Cytochrome synthesis in synchronous cultures of the yeast, Saccharomyces cerevisiae. The synthesis of cytochromes aa3, b, and c has been investigated during synchronous growth in the yeast, Saccharomyces cerevisiae. These cytochromes increase in concentration continuously throughout each cell cycle, with an approximate doubling in rate during successive cycles. The rates of cytochrome formation are considerably higher in galactose-grown cultures than in cells grown in glucose. Although cytochrome aa3 increases at a continuous rate, its functional counterpart, cytochrome c oxidase, increases in stepwise fashion, with the increments occurring at the beginning of each new cell cycle. Chloramphenicol, a specific inhibitor of intramitochondrial protein synthesis, inhibits the formation of cytochrome aa3 at all stages of the cell cycle, but does not inhibit cytochrome c. Chloramphenicol exhibits a somewhat intermediate effect on cytochrome b synthesis, with transient inhibition occurring only when the drug is added prior to or during the initial part of the first cell cycle. After this time, chloramphenicol had no effect on the rate of cytochrome b synthesis. The data indicate that under our conditions of cell synchrony mitochondrial membrane formation as reflected by increments in mitochondrial cytochromes occurs by continuous accretion of new material throughout the cell cycle. Intramitochondrially synthesized polypeptide products, responsible for the formation of new cytochrome aa3, appear to be synthesized throughout the cell cycle."} {"id": "PMID:165192", "title": "Reduced nicotinamide adenine dinucleotide-nitrate reductase of Chlorella vulgaris. Purification, prosthetic groups, and molecular properties.", "content": "NADH:nitrate reductase (EC 1.6.6.1) from Chlorella vulgaris has been purified 640-fold with an over-all yield of 26% by a combination of protamine sulfate fractionation, ammonium sulfate fractionation, gel chromatography, density gradient centrifugation, and DEAE-chromatography. The purified enzyme is stable for more than 2 months when stored at minus 20 degrees in phosphate buffer (pH 6.9) containing 40% (v/v) glycerol. After the initial steps of the purification, a constant ratio of NADH:nitrate reductase activity to NADH:cytochrome c reductase and reduced methyl viologen:nitrate reductase activities was observed. One band of protein was detected after polyacrylamide gel electrophoresis of the purified enzyme. This band also gave a positive stain for heme, NADH dehydrogenase, and reduced methyl viologen:nitrate reductase. One band, corresponding to a molecular weight of 100, 000, was detected after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme contains FAD, heme, and molybdenum in a 1:1:0.8 ratio. One \"cyanide binding site\" per molybdenum was found. No non-heme-iron or labile sulfide was detected. From a dry weight determination of the purified enzyme, a minimal molecular weight of 152, 000 per molecule of heme or FAD was calculated. An s20, w of 9.7 S for nitrate reductase was found by the use of sucrose density gradient centrifugation and a Stokes radius of 89 A was estimated by gel filtration techniques. From these values, and the assumption that the partial specific volume is 0.725 cc/g, a molecular weight of 356, 000 was estimated for the native enzyme. These data suggest that the native enzyme contains a minimum of 2 molecules each of FAD, heme, and molybdenum and is composed of at least three subunits.", "contents": "Reduced nicotinamide adenine dinucleotide-nitrate reductase of Chlorella vulgaris. Purification, prosthetic groups, and molecular properties. NADH:nitrate reductase (EC 1.6.6.1) from Chlorella vulgaris has been purified 640-fold with an over-all yield of 26% by a combination of protamine sulfate fractionation, ammonium sulfate fractionation, gel chromatography, density gradient centrifugation, and DEAE-chromatography. The purified enzyme is stable for more than 2 months when stored at minus 20 degrees in phosphate buffer (pH 6.9) containing 40% (v/v) glycerol. After the initial steps of the purification, a constant ratio of NADH:nitrate reductase activity to NADH:cytochrome c reductase and reduced methyl viologen:nitrate reductase activities was observed. One band of protein was detected after polyacrylamide gel electrophoresis of the purified enzyme. This band also gave a positive stain for heme, NADH dehydrogenase, and reduced methyl viologen:nitrate reductase. One band, corresponding to a molecular weight of 100, 000, was detected after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme contains FAD, heme, and molybdenum in a 1:1:0.8 ratio. One \"cyanide binding site\" per molybdenum was found. No non-heme-iron or labile sulfide was detected. From a dry weight determination of the purified enzyme, a minimal molecular weight of 152, 000 per molecule of heme or FAD was calculated. An s20, w of 9.7 S for nitrate reductase was found by the use of sucrose density gradient centrifugation and a Stokes radius of 89 A was estimated by gel filtration techniques. From these values, and the assumption that the partial specific volume is 0.725 cc/g, a molecular weight of 356, 000 was estimated for the native enzyme. These data suggest that the native enzyme contains a minimum of 2 molecules each of FAD, heme, and molybdenum and is composed of at least three subunits."} {"id": "PMID:165193", "title": "Progesterone binding components of chick oviduct. X. Purification by affinity chromatography.", "content": "Cytoplasmic progesterone receptors of chick oviduct have been purified in 8% yield by steroid affinity and ion exchange chromatography. The affinity resin, deoxycorticosterone-bovine serum albumin-Sepharose, binds progesterone receptors with high affinity (KD equals 8 times 10-minus 10 M) and its use resulted in a greater than 2000-fold purification over the starting material in a single step. DEAE-Sephadex A-50 chromatography was then used to achieve final purification. NA dodecyl-SO4 gel electrophoresis and DEAE-cellulose chromatography showed that the purified receptors contained both of the previously described 4 S progesterone binding components in near equal amounts. Na dodocyl-SO4 gel electrophoresis also showed that these components consisted of single polypeptide chains with molecular weights of 110, 000 (A component) and 117, 000 (B component). There was no evidence for subunits of lower molecular weight. The purified materials have identical hormone-binding kinetics and steroid specificity to crude cytosol receptors. The isolated receptors retain the three biologically important properties exhibited by progesterone binding components present in cruder preparations: they bind specifically to (a) nuclei (KD equals 1.1 times 10-minus 9 M, 10, 000 sites per nucleus); (b) chromatin (KD equals 3 times 10-minus 9 M, 2000 sites per pg of DNA-);and (C) DNA.", "contents": "Progesterone binding components of chick oviduct. X. Purification by affinity chromatography. Cytoplasmic progesterone receptors of chick oviduct have been purified in 8% yield by steroid affinity and ion exchange chromatography. The affinity resin, deoxycorticosterone-bovine serum albumin-Sepharose, binds progesterone receptors with high affinity (KD equals 8 times 10-minus 10 M) and its use resulted in a greater than 2000-fold purification over the starting material in a single step. DEAE-Sephadex A-50 chromatography was then used to achieve final purification. NA dodecyl-SO4 gel electrophoresis and DEAE-cellulose chromatography showed that the purified receptors contained both of the previously described 4 S progesterone binding components in near equal amounts. Na dodocyl-SO4 gel electrophoresis also showed that these components consisted of single polypeptide chains with molecular weights of 110, 000 (A component) and 117, 000 (B component). There was no evidence for subunits of lower molecular weight. The purified materials have identical hormone-binding kinetics and steroid specificity to crude cytosol receptors. The isolated receptors retain the three biologically important properties exhibited by progesterone binding components present in cruder preparations: they bind specifically to (a) nuclei (KD equals 1.1 times 10-minus 9 M, 10, 000 sites per nucleus); (b) chromatin (KD equals 3 times 10-minus 9 M, 2000 sites per pg of DNA-);and (C) DNA."} {"id": "PMID:165194", "title": "Ribulose diphosphate carboxylase/oxygenase. IV. Regulation by phosphate esters.", "content": "The stimulation or inhibition of ribulose diphosphate oxygenase by a variety of compounds is compared with the reported effects on these compounds on the ribulose diphosphate carboxylase activity. A possible transition state analog of ribulose diphosphate, 2-carboxyribitol 1, 5-diphosphate, at a molar ratio of inhibitor to enzyme of 10 to 1, irreversibly inactivates the oxygenase and carboxylase activities. This is consistent with the hypothesis that there may be a single active site for both the carboxylase and oxygenase activities. Several compounds of the reductive pentose photosynthetic carbon cycle act as effectors of the ribulose diphosphate oxygenase in a manner complementary to their reported effect upon the carboxylase. Ribose 5-phosphate inhibits the oxygenase with an apparent Ki of 1.8 mM, but it is reported to activate the carboxylase; fructose 6-phosphate and glucose 6-phosphate act similarly but are less effective than ribose 5-phosphate. Fructose 1. 6-diphosphate stimulates the oxygenase at low magnesium ion concentrations. The stimulatory effect of 6-phosphogluconate on the oxygenase is associated with a 3-fold reduction of the Km (Mg2+). ATP inhibits the oxygenase but has been reported to stimulate the carboxylase; pyrophosphate acts in an opposite manner. From these results it appears that the ratio of carboxylase to oxygenase activity may be a variable factor with predictable subsequent alteration in the ratio between photosynthetic CO2 fixation and photorespiration.", "contents": "Ribulose diphosphate carboxylase/oxygenase. IV. Regulation by phosphate esters. The stimulation or inhibition of ribulose diphosphate oxygenase by a variety of compounds is compared with the reported effects on these compounds on the ribulose diphosphate carboxylase activity. A possible transition state analog of ribulose diphosphate, 2-carboxyribitol 1, 5-diphosphate, at a molar ratio of inhibitor to enzyme of 10 to 1, irreversibly inactivates the oxygenase and carboxylase activities. This is consistent with the hypothesis that there may be a single active site for both the carboxylase and oxygenase activities. Several compounds of the reductive pentose photosynthetic carbon cycle act as effectors of the ribulose diphosphate oxygenase in a manner complementary to their reported effect upon the carboxylase. Ribose 5-phosphate inhibits the oxygenase with an apparent Ki of 1.8 mM, but it is reported to activate the carboxylase; fructose 6-phosphate and glucose 6-phosphate act similarly but are less effective than ribose 5-phosphate. Fructose 1. 6-diphosphate stimulates the oxygenase at low magnesium ion concentrations. The stimulatory effect of 6-phosphogluconate on the oxygenase is associated with a 3-fold reduction of the Km (Mg2+). ATP inhibits the oxygenase but has been reported to stimulate the carboxylase; pyrophosphate acts in an opposite manner. From these results it appears that the ratio of carboxylase to oxygenase activity may be a variable factor with predictable subsequent alteration in the ratio between photosynthetic CO2 fixation and photorespiration."} {"id": "PMID:165195", "title": "Nucleolar changes in liver before the onset of deoxyribonucleic acid replication.", "content": "A mixture of chemicals was previously devised (3, 3', 5'-triiodo-L-thyronine, amino acids, a butyryl derivative of cyclic adenosine 3':5'-monophosphate, theophylline, and heparin) that induces nuclear DNA replication in the liver of the unoperated rat (Short, J., Tsukada, K., Rudert, W.A. 7 Lieberman, I. (1975) J. Biol. Chem. 250, 3602-3606). The stimulation of DNA synthesis with the complete solution is greater than the sum of the responses to the thyroid hormone alone and to a mixture of the remaining components of the inductive solution alone. The effects of the complete mixture and of parts of it on three parameters involving the hepatocyte nucleolus have now been examined in intact animals. The complete solution increases the level of RNA polymerase I (measured with isolated nuclei), the rate of ribosome synthesis, and the total volume of nucleoli per nucleus. Nucleolar hypertrophy is unique among the three changes in showing a requirement, just as for DNA synthesis, for all or almost all of the components of the complete mixture, including the thyroid hormone, for a maximal effect. Enlargement of nucleoli is detectable as early as 2 hours after the start of treatment with the complete mixture and a large proportion of the total hepatocyte population is involved. Hypertrophy is accompanied by an increase in nucleolar RNA content. N2-Monobutyryl cyclic guanosine 3':5'-monophosphate is not able to substitute for the cyclic adenine nucleotide.", "contents": "Nucleolar changes in liver before the onset of deoxyribonucleic acid replication. A mixture of chemicals was previously devised (3, 3', 5'-triiodo-L-thyronine, amino acids, a butyryl derivative of cyclic adenosine 3':5'-monophosphate, theophylline, and heparin) that induces nuclear DNA replication in the liver of the unoperated rat (Short, J., Tsukada, K., Rudert, W.A. 7 Lieberman, I. (1975) J. Biol. Chem. 250, 3602-3606). The stimulation of DNA synthesis with the complete solution is greater than the sum of the responses to the thyroid hormone alone and to a mixture of the remaining components of the inductive solution alone. The effects of the complete mixture and of parts of it on three parameters involving the hepatocyte nucleolus have now been examined in intact animals. The complete solution increases the level of RNA polymerase I (measured with isolated nuclei), the rate of ribosome synthesis, and the total volume of nucleoli per nucleus. Nucleolar hypertrophy is unique among the three changes in showing a requirement, just as for DNA synthesis, for all or almost all of the components of the complete mixture, including the thyroid hormone, for a maximal effect. Enlargement of nucleoli is detectable as early as 2 hours after the start of treatment with the complete mixture and a large proportion of the total hepatocyte population is involved. Hypertrophy is accompanied by an increase in nucleolar RNA content. N2-Monobutyryl cyclic guanosine 3':5'-monophosphate is not able to substitute for the cyclic adenine nucleotide."} {"id": "PMID:165196", "title": "Superoxide production and electron transport in mitochondrial oxidation of dihydroorotic acid.", "content": "Production of superoxide radical during oxidation of dihydroorotate in rat liver mitochondria was not affected by antimycin A, thenoyltrifluoroacetone, or added ubiquinone but was inhibited by orotate, a product inhibitor of dihydroorotate dehydrogenase. It appears likely that superoxide is generated at the primary dehydrogenase. Dihydroorotate dehydrogenase differs from succinate dehydrogenase both in its utilization of ubiquinone and in the mechanism of cytochrome b reduction. Thenoyltrifluoroacetone completely inhibits fumarate synthesis and reduction of cytochrome b by succinate. Formation of orotate is only partially inhibited by thenolytrifluoroacetone and the inhibitor does not prevent reduction of cytochrome b by dihydroorotate. It is proposed that several pathways exist for linkage of the primary dihydrorotate dehydrogenase with the electron transport chain. One route involves electron transfer from ubiquinone to cytochrome c and is inhibited by thenoyltrifluoroacetone. A second route bypasses ubiquinone and is inhibited by antimycin A. A third pathway utilizes both ubiquinone and cytochrome b and is partiayly inhibited by either thenoyltrifluoroacetone or antimycin A.", "contents": "Superoxide production and electron transport in mitochondrial oxidation of dihydroorotic acid. Production of superoxide radical during oxidation of dihydroorotate in rat liver mitochondria was not affected by antimycin A, thenoyltrifluoroacetone, or added ubiquinone but was inhibited by orotate, a product inhibitor of dihydroorotate dehydrogenase. It appears likely that superoxide is generated at the primary dehydrogenase. Dihydroorotate dehydrogenase differs from succinate dehydrogenase both in its utilization of ubiquinone and in the mechanism of cytochrome b reduction. Thenoyltrifluoroacetone completely inhibits fumarate synthesis and reduction of cytochrome b by succinate. Formation of orotate is only partially inhibited by thenolytrifluoroacetone and the inhibitor does not prevent reduction of cytochrome b by dihydroorotate. It is proposed that several pathways exist for linkage of the primary dihydrorotate dehydrogenase with the electron transport chain. One route involves electron transfer from ubiquinone to cytochrome c and is inhibited by thenoyltrifluoroacetone. A second route bypasses ubiquinone and is inhibited by antimycin A. A third pathway utilizes both ubiquinone and cytochrome b and is partiayly inhibited by either thenoyltrifluoroacetone or antimycin A."} {"id": "PMID:165197", "title": "Synthesis of Superhelical Simian Virus 40 Deoxyribonucleic Acid in Cell Lysates*.", "content": "In vivo-labeled SV40 replicating DNA molecules can be converted into covalently closed superhelical SV40 DNA (SV40(I) using a lysate of sv40-infected monkey cells containing intact nuclei. Replication in vitro occurred at one-third the in vivo rate for 30 min at 30 degrees. After 1 hour of incubation, about 54% of the replicating molecules had been converted to SV40(I), 5% to nicked, circular molecules (SV40(II), 5% to covalently closed dimers; the remainder failed to complete replication although 75% of the prelabeled daughter strands had been elongated to one-genome length. Density labeling in vitro showed that all replicating molecules had participated during DNA synthesis in vitro. Velocity and equilibrium sedimentation analysis of pulse-chased and labeled DNA using radioactive and density labels suggested that SV40 DNA synthesis in vitro was a continuation of normal ongoing DNA synthesis. Initiation of new rounds of SV40 DNA replication was not detectable.", "contents": "Synthesis of Superhelical Simian Virus 40 Deoxyribonucleic Acid in Cell Lysates*. In vivo-labeled SV40 replicating DNA molecules can be converted into covalently closed superhelical SV40 DNA (SV40(I) using a lysate of sv40-infected monkey cells containing intact nuclei. Replication in vitro occurred at one-third the in vivo rate for 30 min at 30 degrees. After 1 hour of incubation, about 54% of the replicating molecules had been converted to SV40(I), 5% to nicked, circular molecules (SV40(II), 5% to covalently closed dimers; the remainder failed to complete replication although 75% of the prelabeled daughter strands had been elongated to one-genome length. Density labeling in vitro showed that all replicating molecules had participated during DNA synthesis in vitro. Velocity and equilibrium sedimentation analysis of pulse-chased and labeled DNA using radioactive and density labels suggested that SV40 DNA synthesis in vitro was a continuation of normal ongoing DNA synthesis. Initiation of new rounds of SV40 DNA replication was not detectable."} {"id": "PMID:165198", "title": "Requirement of a Cytoplasmic Fraction for Synthesis of SV40 Deoxyribonucleic Acid in Isolated Nuclei*.", "content": "About 50% of the SV40 DNA in the process of replication (sv40(ri) dna) completed replication in lysates of infected BSC-1 cells by conversion to covalently closed, superhelical SV40 DNA (SV40(I) DNA). Fractionation of the lysate into nuclear and cytoplasmic components blocked 99% of the synthesis of SV40(I) DNA in the purified nuclei. The reconstituted system, made by adding back the cytoplasmic fraction before incubation at 30 degrees, completely restored the in vitro level of SV40(I) DNA synthesis. Preliminary characterization of the activity found in the cytoplasmic fraction suggested it was a soluble, heat-labile protein (or proteins) with a minimum molecular weight of about 30,000 and an active sulfhydryl group. The activity was present in both infected and uninfected monkey cells, and at a lower level in mouse, hamster, and human cell lines. Neither serum starvation nor cycloheximide treatment of cells diminished the activity in the cytoplasmic fraction. Purified cytoplasmic DNA polymerase from KB cells did not substitute for the cytoplasmic fraction which was required for elongation of newly synthesized DNA strands. In the absence of the cytoplasmic fraction, conversion of 4 S DNA into longer strands was inhibited, and SV40(RI) DNA appeared to be broken specifically at the replication forks.", "contents": "Requirement of a Cytoplasmic Fraction for Synthesis of SV40 Deoxyribonucleic Acid in Isolated Nuclei*. About 50% of the SV40 DNA in the process of replication (sv40(ri) dna) completed replication in lysates of infected BSC-1 cells by conversion to covalently closed, superhelical SV40 DNA (SV40(I) DNA). Fractionation of the lysate into nuclear and cytoplasmic components blocked 99% of the synthesis of SV40(I) DNA in the purified nuclei. The reconstituted system, made by adding back the cytoplasmic fraction before incubation at 30 degrees, completely restored the in vitro level of SV40(I) DNA synthesis. Preliminary characterization of the activity found in the cytoplasmic fraction suggested it was a soluble, heat-labile protein (or proteins) with a minimum molecular weight of about 30,000 and an active sulfhydryl group. The activity was present in both infected and uninfected monkey cells, and at a lower level in mouse, hamster, and human cell lines. Neither serum starvation nor cycloheximide treatment of cells diminished the activity in the cytoplasmic fraction. Purified cytoplasmic DNA polymerase from KB cells did not substitute for the cytoplasmic fraction which was required for elongation of newly synthesized DNA strands. In the absence of the cytoplasmic fraction, conversion of 4 S DNA into longer strands was inhibited, and SV40(RI) DNA appeared to be broken specifically at the replication forks."} {"id": "PMID:165199", "title": "Hydrophobic interaction of alkanes with liposomes and lipoproteins.", "content": "Human serum lipoproteins and egg yolk lecithin liposomes are able to solubilize large amounts of n-hexane and n-octane. At the maximum water solubility of n-octane the mole ratio of alkane to lipoprotein was 65 for high density lipoprotein (holo-HDL) and 900 for low density lipoprotein (holo-LDL). Alkane binding to lipid-free apo-HDL is negligible compared to alkane solubility in holo-HDL. Alkane solubility in the lipoproteins and liposomes is thermodynamically consistent with the simple soution of hydrocarbon in the hydrophobic regions of these particles. The unitary free energies of alkane transfer are similar to values previously observed for detergent micelles but are less favorable by 0.8 kcal/mol from the free energy of transfer to liquid hydrocarbon. It is concluded that the thermodynamics of alkane transfer to the lipoproteins resembles that found for detergent micelles or liposomes rather than that anticipated for an \"oil drop\" (i.e. liquid hydrocarbon).", "contents": "Hydrophobic interaction of alkanes with liposomes and lipoproteins. Human serum lipoproteins and egg yolk lecithin liposomes are able to solubilize large amounts of n-hexane and n-octane. At the maximum water solubility of n-octane the mole ratio of alkane to lipoprotein was 65 for high density lipoprotein (holo-HDL) and 900 for low density lipoprotein (holo-LDL). Alkane binding to lipid-free apo-HDL is negligible compared to alkane solubility in holo-HDL. Alkane solubility in the lipoproteins and liposomes is thermodynamically consistent with the simple soution of hydrocarbon in the hydrophobic regions of these particles. The unitary free energies of alkane transfer are similar to values previously observed for detergent micelles but are less favorable by 0.8 kcal/mol from the free energy of transfer to liquid hydrocarbon. It is concluded that the thermodynamics of alkane transfer to the lipoproteins resembles that found for detergent micelles or liposomes rather than that anticipated for an \"oil drop\" (i.e. liquid hydrocarbon)."} {"id": "PMID:165200", "title": "Regulation of adenosine 3' :5'-monophosphate efflux from rat glioma cells in culture*.", "content": "Rat glioma cells grown in culture secrete cyclic adenosine 3':5'-monophosphate (cyclic AMP) into the culture medium following stimulation by beta-agonistic catecholamines. Agents which reduced cellular ATP levels such as valinomycin, oligomycin, and uncouplers of oxidative phosphorylation, inhibited cyclic AMP efflux. Secretion of cyclic AMP was also prevented by prostaglandin A-1 and pharmacological agents including probenecid and papaverine. Of the latter agents, only papaverine reduced ATP levels. These results suggest that the transport of cyclic AMP across animal cell membranes is energy-dependent and subject to regulation.", "contents": "Regulation of adenosine 3' :5'-monophosphate efflux from rat glioma cells in culture*. Rat glioma cells grown in culture secrete cyclic adenosine 3':5'-monophosphate (cyclic AMP) into the culture medium following stimulation by beta-agonistic catecholamines. Agents which reduced cellular ATP levels such as valinomycin, oligomycin, and uncouplers of oxidative phosphorylation, inhibited cyclic AMP efflux. Secretion of cyclic AMP was also prevented by prostaglandin A-1 and pharmacological agents including probenecid and papaverine. Of the latter agents, only papaverine reduced ATP levels. These results suggest that the transport of cyclic AMP across animal cell membranes is energy-dependent and subject to regulation."} {"id": "PMID:165205", "title": "Pitfalls in the use of lead nitrate for the histochemical demonstration of adenylate cyclase activity.", "content": "The biochemistry of the lead histochemical technique for demonstrating adenylate cyclase was studied. The enzyme activity of fat cell plasma membranes, using 5'-adenylyl-imidodiphosphate (AMP-PNP) as substrate, was completely inhibited at 1 times 10- minus 4 M Pb(NO3)2 and yet at 4 times 10- minus 3 M Pb(NO3)2 precipitate could be demonstrated by electron microscopy on both sides of plasma membrane vesicles. No lead-diphosphoimide or lead-phosphate precipitate could be visualized by electron microscopy when the lead was reduced to a level (2 times 10- minus 5 M) which caused only 50% inhibition of the enzyme. A solubility product coefficient of 1 times 10- minus 10 M was found necessary to allow precipitation of lead-phosphate complex in the adenylate cyclase medium. Varying the ratio of substrate or dextran relative to the lead failed to protect the inhibition of the enzyme. Increasing concentrations of beta-mercaptoethanol restored the basal and stimulated activity of adenylate cyclase but also prevented the precipitation reaction. Lead at 2 times 10- minus 3 M caused the nonenzymatic hydrolysis of AMP-PNP, resulting in the production of small but significant quantities of cyclic AMP and substantial amounts of AMP. This hydrolysis was inhibited by alloxan but unaffected by dextran of NaF. The adenylate cyclase activity of pancreatic islet homogenates and of fat pad capillaries was completely inhibited by lead concentrations equal to or less than those used in histochemical studies (Howell, S. L., and M. Whitfield. 1972. J. Histochem. Cytochem. 20:873-879. and Wagner, R. C., P. Kreiner, R. J. Barrnett, and M. W. Bitensky. 1972. Proc. Natl. Acad. Sci. U.S.A. 69:3175-3179.). The present study shows that the lead histochemical method cannot be used for localization of adenylate cyclase because of the inhibition of the enzyme and artifacts produced by high lead concentrations and the inability to produce a visible precipitate at low lead concentrations which only partially inhibit the enzyme.", "contents": "Pitfalls in the use of lead nitrate for the histochemical demonstration of adenylate cyclase activity. The biochemistry of the lead histochemical technique for demonstrating adenylate cyclase was studied. The enzyme activity of fat cell plasma membranes, using 5'-adenylyl-imidodiphosphate (AMP-PNP) as substrate, was completely inhibited at 1 times 10- minus 4 M Pb(NO3)2 and yet at 4 times 10- minus 3 M Pb(NO3)2 precipitate could be demonstrated by electron microscopy on both sides of plasma membrane vesicles. No lead-diphosphoimide or lead-phosphate precipitate could be visualized by electron microscopy when the lead was reduced to a level (2 times 10- minus 5 M) which caused only 50% inhibition of the enzyme. A solubility product coefficient of 1 times 10- minus 10 M was found necessary to allow precipitation of lead-phosphate complex in the adenylate cyclase medium. Varying the ratio of substrate or dextran relative to the lead failed to protect the inhibition of the enzyme. Increasing concentrations of beta-mercaptoethanol restored the basal and stimulated activity of adenylate cyclase but also prevented the precipitation reaction. Lead at 2 times 10- minus 3 M caused the nonenzymatic hydrolysis of AMP-PNP, resulting in the production of small but significant quantities of cyclic AMP and substantial amounts of AMP. This hydrolysis was inhibited by alloxan but unaffected by dextran of NaF. The adenylate cyclase activity of pancreatic islet homogenates and of fat pad capillaries was completely inhibited by lead concentrations equal to or less than those used in histochemical studies (Howell, S. L., and M. Whitfield. 1972. J. Histochem. Cytochem. 20:873-879. and Wagner, R. C., P. Kreiner, R. J. Barrnett, and M. W. Bitensky. 1972. Proc. Natl. Acad. Sci. U.S.A. 69:3175-3179.). The present study shows that the lead histochemical method cannot be used for localization of adenylate cyclase because of the inhibition of the enzyme and artifacts produced by high lead concentrations and the inability to produce a visible precipitate at low lead concentrations which only partially inhibit the enzyme."} {"id": "PMID:165206", "title": "Calcium and pancreatic secretion. I. Subcellular distribution of calcium and magnesium in the exocrine pancreas of the guinea pig.", "content": "The distribution of calcium and magnesium has been studied in the acinar cells of the pancreas of the guinea pig. Most of the magnesium was found to be associated with the rough microsomes (probably bound to the ribosomes) and with the postmicrosomal supernate. In contrast, calcium was distributed among all the particulate fractions, primarily the mitochondria, microsomes (especially smooth surfaced), zymogen granules, and the plasmalemma, and was low in the postmicrosomal supernate. Most of the calcium recovered in the particulate fractions was found to be membrane bound. The highest concentrations were found in the membranes of the zymogen granules and in the plasmalemma. By means of control experiments using -45Ca as the tracer, it was established that a considerable redistribution of calcium occurs during homogenization and cell fractionation. At least some of the resulting artifacts were estimated quantitatively and the data were corrected accordingly. The biochemical results were confirmed with the cytochemical antimonate technique carried out on the tissue as well as on isolated fractions. The role of calcium associated with the zymogen granules and with their limiting membranes is discussed in relation to the architecture of the granule and to the functionality of the pancreatic juice.", "contents": "Calcium and pancreatic secretion. I. Subcellular distribution of calcium and magnesium in the exocrine pancreas of the guinea pig. The distribution of calcium and magnesium has been studied in the acinar cells of the pancreas of the guinea pig. Most of the magnesium was found to be associated with the rough microsomes (probably bound to the ribosomes) and with the postmicrosomal supernate. In contrast, calcium was distributed among all the particulate fractions, primarily the mitochondria, microsomes (especially smooth surfaced), zymogen granules, and the plasmalemma, and was low in the postmicrosomal supernate. Most of the calcium recovered in the particulate fractions was found to be membrane bound. The highest concentrations were found in the membranes of the zymogen granules and in the plasmalemma. By means of control experiments using -45Ca as the tracer, it was established that a considerable redistribution of calcium occurs during homogenization and cell fractionation. At least some of the resulting artifacts were estimated quantitatively and the data were corrected accordingly. The biochemical results were confirmed with the cytochemical antimonate technique carried out on the tissue as well as on isolated fractions. The role of calcium associated with the zymogen granules and with their limiting membranes is discussed in relation to the architecture of the granule and to the functionality of the pancreatic juice."} {"id": "PMID:165207", "title": "Colchicine resistance in mammalian cell lines.", "content": "Colchicine-resistant variants derived from mouse and Syrian hamster lines are described. The resistant cells do not appear to be true mutants, since they appear at a high frequency, unaffected by treatment with ethyl methyl sulphonate, and are unstable in the absence of the drug. They are cross-resistant to other drugs, show a reduced rate of binding of colchicine in monolayer, and give extracts with colchicine-binding properties identical to those of the wild type. Thus the resistance is due to a permeability barrier. The naturally occurring resistance of the Syrian hamster line is specific for colchicine, and may be due to a specific permeability barrier. The Syrian hamster line is also shown to have an extra colchicine-binding pool.", "contents": "Colchicine resistance in mammalian cell lines. Colchicine-resistant variants derived from mouse and Syrian hamster lines are described. The resistant cells do not appear to be true mutants, since they appear at a high frequency, unaffected by treatment with ethyl methyl sulphonate, and are unstable in the absence of the drug. They are cross-resistant to other drugs, show a reduced rate of binding of colchicine in monolayer, and give extracts with colchicine-binding properties identical to those of the wild type. Thus the resistance is due to a permeability barrier. The naturally occurring resistance of the Syrian hamster line is specific for colchicine, and may be due to a specific permeability barrier. The Syrian hamster line is also shown to have an extra colchicine-binding pool."} {"id": "PMID:165208", "title": "The liquid chromatographic properties of phenothiazines.", "content": "The high-pressure liquid chromatographic behaviour of different groups of phenothiazines (drug substances) has been investigated on 10-mu m silica gel particles. Variation of the ammonia concentration between 0.5 and 1.5% in an isopropanol-diisopropyl ether (15:85) mixture permits the adjustment of the solvent system to fit the different basicities of the various groups of interest. While the capacity factors (k') for pairs of compounds in two homologous oxidation series vary considerably owing to differences in basicity, there is reasonably good agreement between the relative retention (alphs) values. This fact can be utilized in order to identify phenothiazine homologues of series that have not previously been studied. Elutropic diagrams in connection with alpha values can be used to predict the chromatographic behaviour of new groups of phenothiazines.", "contents": "The liquid chromatographic properties of phenothiazines. The high-pressure liquid chromatographic behaviour of different groups of phenothiazines (drug substances) has been investigated on 10-mu m silica gel particles. Variation of the ammonia concentration between 0.5 and 1.5% in an isopropanol-diisopropyl ether (15:85) mixture permits the adjustment of the solvent system to fit the different basicities of the various groups of interest. While the capacity factors (k') for pairs of compounds in two homologous oxidation series vary considerably owing to differences in basicity, there is reasonably good agreement between the relative retention (alphs) values. This fact can be utilized in order to identify phenothiazine homologues of series that have not previously been studied. Elutropic diagrams in connection with alpha values can be used to predict the chromatographic behaviour of new groups of phenothiazines."} {"id": "PMID:165210", "title": "Urinary excretion of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in normal children and those with cystic fibrosis.", "content": "The urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was examined in 98 normal children and 46 children with cystic fibrosis between the ages of 9 months and 18 yr. Diurnal variations in cyclic AMP and cyclic GMP excretion were observed in subjects from either group, and peak levels of cyclic nucleotide excretion were generally observed during the period of 0700 to 2100 h. Excretion rates (mumol/day) of cyclic AMP and cyclic GMP increased significantly with age. When cyclic AMP and cyclic GMP excretion rates were normalized for urinary creatine, or body weight, the values declined significantly with age in both groups of patients. Cyclic GMP excretion normalized for body surface area also decreased with age, while the value for cyclic AMP (2.86 plus or minus 0.08 mumol/day/m2, mean plus or minus SE) was constant with age in both normals and cystic fibrosis children. With some comparisons of age groups there were significant differences in cyclic nucleotide excretion between normal subjects and children with cystic fibrosis. The differences noted were dependent upon the methods used to normalize excretion rates (urinary creatine, body weight, surface area, and the ratio of cyclic AMP to cyclic GMP excreated). In general patients with cystic fibrosis excreted greater amounts of cyclic GMP than did normals. The most striking comparison was the ratio of cyclic AMP to cyclic GMP excreted which was 9.09 plus or minus 0.50 in all normal children and 4.41 plus or minus 0.32 in children with cystic fibrosis (P smaller than 0.001).", "contents": "Urinary excretion of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in normal children and those with cystic fibrosis. The urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was examined in 98 normal children and 46 children with cystic fibrosis between the ages of 9 months and 18 yr. Diurnal variations in cyclic AMP and cyclic GMP excretion were observed in subjects from either group, and peak levels of cyclic nucleotide excretion were generally observed during the period of 0700 to 2100 h. Excretion rates (mumol/day) of cyclic AMP and cyclic GMP increased significantly with age. When cyclic AMP and cyclic GMP excretion rates were normalized for urinary creatine, or body weight, the values declined significantly with age in both groups of patients. Cyclic GMP excretion normalized for body surface area also decreased with age, while the value for cyclic AMP (2.86 plus or minus 0.08 mumol/day/m2, mean plus or minus SE) was constant with age in both normals and cystic fibrosis children. With some comparisons of age groups there were significant differences in cyclic nucleotide excretion between normal subjects and children with cystic fibrosis. The differences noted were dependent upon the methods used to normalize excretion rates (urinary creatine, body weight, surface area, and the ratio of cyclic AMP to cyclic GMP excreated). In general patients with cystic fibrosis excreted greater amounts of cyclic GMP than did normals. The most striking comparison was the ratio of cyclic AMP to cyclic GMP excreted which was 9.09 plus or minus 0.50 in all normal children and 4.41 plus or minus 0.32 in children with cystic fibrosis (P smaller than 0.001)."} {"id": "PMID:165211", "title": "Reversible hypothyroidism in growth hormone-deficient children treated with human growth hormone.", "content": "Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.", "contents": "Reversible hypothyroidism in growth hormone-deficient children treated with human growth hormone. Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH."} {"id": "PMID:165212", "title": "Radioligand receptor assay for urinary and serum hCG.", "content": "A radioligand receptor assay system for urinary hCG and serum hCG was developed, using 1100-2000 times g fractions of homogenates of pig testis. This method is specific for hCG and LH, and the limit of detection for hCG was 20 mIU, which could be significantly discriminated from zero at the 95% confidence level. A nonspecific inhibition reaction which exerts its influence on the assay system has been found in the urine and serum, and in performing assays for urinary and serum hCG, it was necessary to remove the inhibition reaction by diluting the urine more than eight fold or subject the serum to an extraction procedure. Since the hCG of normal pregnancy and trophoblastic neoplasia showed a dose response curve similar to that of the International Standard hCG, it became clear that these hCG could be assayed with this method. The potency ratio R/I measured by RRA and RIA of urinary hCG and serum hCG was different from those of normal pregnancy and trophoblastic neoplasia.", "contents": "Radioligand receptor assay for urinary and serum hCG. A radioligand receptor assay system for urinary hCG and serum hCG was developed, using 1100-2000 times g fractions of homogenates of pig testis. This method is specific for hCG and LH, and the limit of detection for hCG was 20 mIU, which could be significantly discriminated from zero at the 95% confidence level. A nonspecific inhibition reaction which exerts its influence on the assay system has been found in the urine and serum, and in performing assays for urinary and serum hCG, it was necessary to remove the inhibition reaction by diluting the urine more than eight fold or subject the serum to an extraction procedure. Since the hCG of normal pregnancy and trophoblastic neoplasia showed a dose response curve similar to that of the International Standard hCG, it became clear that these hCG could be assayed with this method. The potency ratio R/I measured by RRA and RIA of urinary hCG and serum hCG was different from those of normal pregnancy and trophoblastic neoplasia."} {"id": "PMID:165213", "title": "Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children.", "content": "To evaluate the relationship between the secretion of gonadotropins and adrenal androgens, patients with gonadal agenesis were evaluated by (a) administering human luteinizing hormone (hLH) for 5 days with or without estrogen pretreatment to agonadal patients who had prepubertal LH levels; (b) correlating circulating gonadotropin levels with adrenal androgens in 45 patients; and (c) comparing adrenal androgens with gonadotropins after long-term administration of estrogen or androgens. Results are as follows: (a) No alteration in serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), estrone (E1), testosterone (T), or in excretion of urinary 17-ketosteroid (17 KS) occurred after the administration of hLH. (b) No clearcut relationship between endogenous level of LH or FSH and DHA OR DHAS was demonstrated although a coincident increase of all hormones with age occurred. (c) Administration of estrogen to patients with gonadal agenesis did not affect their levels of DHA and DHAS although those patients given androgen developed higher DHAS, but not DHA, levels. Hence, increasing gonadotropin concentrations would not appear to be a primary etiologic factor in the maturation of the adrenal.", "contents": "Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children. To evaluate the relationship between the secretion of gonadotropins and adrenal androgens, patients with gonadal agenesis were evaluated by (a) administering human luteinizing hormone (hLH) for 5 days with or without estrogen pretreatment to agonadal patients who had prepubertal LH levels; (b) correlating circulating gonadotropin levels with adrenal androgens in 45 patients; and (c) comparing adrenal androgens with gonadotropins after long-term administration of estrogen or androgens. Results are as follows: (a) No alteration in serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), estrone (E1), testosterone (T), or in excretion of urinary 17-ketosteroid (17 KS) occurred after the administration of hLH. (b) No clearcut relationship between endogenous level of LH or FSH and DHA OR DHAS was demonstrated although a coincident increase of all hormones with age occurred. (c) Administration of estrogen to patients with gonadal agenesis did not affect their levels of DHA and DHAS although those patients given androgen developed higher DHAS, but not DHA, levels. Hence, increasing gonadotropin concentrations would not appear to be a primary etiologic factor in the maturation of the adrenal."} {"id": "PMID:165214", "title": "Relationship of bioassayable and immunoassayable plasma ACTH and cortisol concentrations in normal subjects and in patients with Cushing's disease.", "content": "Plasma ACTH and cortisol concentrations were determined at 5-min intervals over a 3- or 4-h sampling period in 2 normal subjects. Time spans studied were 10:00 AM-1:00 PM, 4:00 PM-8:00 PM, 8:00 PM-11:00 PM, and 4:00 AM-8:00 AM. Similar sampling for 3 h, (onset 9:00-9:30 AM) was performed on 4 patients with Cushing's disease, 3 untreated and 1 in remission following pituitary irradiation. Two of these patients were studied on 2 separate occasions. Plasma ACTH was determined by both immunoassay (I) and bioassay (B). Although in general, these studies demonstrated significant correlation between I-ACTH or B-ACTH concentrations and those of plasma cortisol, a striking finding in both subject categories was the presence of 30- to 50-min episodes during which marked rises in both I- and B-ACTH concentrations occurred without concomittant, or markedly diminished, increments in plasma cortisol concentrations. This could not be explained by biological inactivity of the ACTH, since a highly significant correlation was present between I- and B-ACTH concentrations at all times; r values ranged between 0.86 and 0.98 for normal subjects, and 0.76 and 0.96 for patients with Cushing's disease. The lack of correlation in these episodes also does not appear to be secondary to an 11-beta-hydroxylase block, differences in the rate of change of plasma ACTH concentrations, lack of adrenal \"priming\" by prior ACTH or incapacity of the adrenal gland to further increase secretion. I/B ACTH ratios were similar in the normal subjects (1.42-1.64) and in the patients with Cushing's disease (1.27-1.47). \"Apparent\" ACTH half lives calculated from \"peaks\" of ACTH secretion were 7-12 min for I-ACTH and 3-9 min for B-ACTH in the normal subjects; and 9-13 min and 7-9 min respectively, in the patients with Cushing's disease. Mean plasma ACTH I-and B-concentrations at comparable time periods were higher in patients with active Cushing's disease than in normal subjects. These studies also indicate that in Cushing's disease, the abnormality present resides in ACTH regulatory mechanisms, not in the nature of the ACTH secreted. Approximation of the total amount of immunoassayable ACTH secreted in one normal subject over a 24-h period yielded a value of 73 mug. Total mug/h secreted in the 2 normal subjects were highest in the hour preceding awakening (6:30-7:30 AM; 12.9 and 12.2 mug/h); were 5.3 and 4.0 mug/h between 10:00-11:00 AM, and 1.4 and 1.7 mug/h between 9:00-10:00 PM. In the 3 patients with clinically active Cushing's disease, apparent ACTH secretion between 10:00-11:00 AM varied from 19.2-34.3 mug/h, the magnitude of such secretion being positively correlated with the extent of increased adrenal cortical activity present.", "contents": "Relationship of bioassayable and immunoassayable plasma ACTH and cortisol concentrations in normal subjects and in patients with Cushing's disease. Plasma ACTH and cortisol concentrations were determined at 5-min intervals over a 3- or 4-h sampling period in 2 normal subjects. Time spans studied were 10:00 AM-1:00 PM, 4:00 PM-8:00 PM, 8:00 PM-11:00 PM, and 4:00 AM-8:00 AM. Similar sampling for 3 h, (onset 9:00-9:30 AM) was performed on 4 patients with Cushing's disease, 3 untreated and 1 in remission following pituitary irradiation. Two of these patients were studied on 2 separate occasions. Plasma ACTH was determined by both immunoassay (I) and bioassay (B). Although in general, these studies demonstrated significant correlation between I-ACTH or B-ACTH concentrations and those of plasma cortisol, a striking finding in both subject categories was the presence of 30- to 50-min episodes during which marked rises in both I- and B-ACTH concentrations occurred without concomittant, or markedly diminished, increments in plasma cortisol concentrations. This could not be explained by biological inactivity of the ACTH, since a highly significant correlation was present between I- and B-ACTH concentrations at all times; r values ranged between 0.86 and 0.98 for normal subjects, and 0.76 and 0.96 for patients with Cushing's disease. The lack of correlation in these episodes also does not appear to be secondary to an 11-beta-hydroxylase block, differences in the rate of change of plasma ACTH concentrations, lack of adrenal \"priming\" by prior ACTH or incapacity of the adrenal gland to further increase secretion. I/B ACTH ratios were similar in the normal subjects (1.42-1.64) and in the patients with Cushing's disease (1.27-1.47). \"Apparent\" ACTH half lives calculated from \"peaks\" of ACTH secretion were 7-12 min for I-ACTH and 3-9 min for B-ACTH in the normal subjects; and 9-13 min and 7-9 min respectively, in the patients with Cushing's disease. Mean plasma ACTH I-and B-concentrations at comparable time periods were higher in patients with active Cushing's disease than in normal subjects. These studies also indicate that in Cushing's disease, the abnormality present resides in ACTH regulatory mechanisms, not in the nature of the ACTH secreted. Approximation of the total amount of immunoassayable ACTH secreted in one normal subject over a 24-h period yielded a value of 73 mug. Total mug/h secreted in the 2 normal subjects were highest in the hour preceding awakening (6:30-7:30 AM; 12.9 and 12.2 mug/h); were 5.3 and 4.0 mug/h between 10:00-11:00 AM, and 1.4 and 1.7 mug/h between 9:00-10:00 PM. In the 3 patients with clinically active Cushing's disease, apparent ACTH secretion between 10:00-11:00 AM varied from 19.2-34.3 mug/h, the magnitude of such secretion being positively correlated with the extent of increased adrenal cortical activity present."} {"id": "PMID:165215", "title": "The effect of melatonin on steroidogenesis by the human ovary in vitro.", "content": "Melatonin stimulated steroidogenesis in two compartments of the human ovary in vitro. In a corpus luteum of the menstrual cycle, melatonin increased progesterone synthesis in a dose related manner. Both serotonin and N-acetyl serotonin had no effect on progesterone synthesis. In the ovarian stroma, melatonin stimulated the incorporation of acetate-1-14-C into androstenedione. Binding of radioactive hCG by the corpus luteum was unaffected by melatonin. No specific binding of radioactive melatonin of low specific activity could be detected in homogenates of a human corpus luteum. These observations suggest that melatonin may directly modulate steroidogenesis in the human ovary.", "contents": "The effect of melatonin on steroidogenesis by the human ovary in vitro. Melatonin stimulated steroidogenesis in two compartments of the human ovary in vitro. In a corpus luteum of the menstrual cycle, melatonin increased progesterone synthesis in a dose related manner. Both serotonin and N-acetyl serotonin had no effect on progesterone synthesis. In the ovarian stroma, melatonin stimulated the incorporation of acetate-1-14-C into androstenedione. Binding of radioactive hCG by the corpus luteum was unaffected by melatonin. No specific binding of radioactive melatonin of low specific activity could be detected in homogenates of a human corpus luteum. These observations suggest that melatonin may directly modulate steroidogenesis in the human ovary."} {"id": "PMID:165216", "title": "Characterization of the glucagon receptor in a pheochromocytoma.", "content": "Glucagon activated adenylate cyclase in a homogenate of a pheochromocytoma over the concentration range 1 times 10 minus 8M to 1 times 10 minus 6M. Several other hormones including adrenocorticotropin, thyrotropin, parathyroid hormone and histamine were without effect. The tumor glucagon receptor was characterized and found to be similar in several ways to the glucagon receptor previously reported in normal tissue such as liver and heart. One, the receptor specifically bound 125-I-glucagon. Two, solubilization of the pheochromocytoma abolished glucagon-activation of the adenylate cyclase. Three, glucagon-responsiveness of the adenylate cyclase was partially restored by the addition of phosphatidylserine to the incubations. One major difference was observed between the glucagon receptor in tumor tissue and that in liver and heart, namely, a marked lability in 125-I-glucagon binding and adenylate cyclase activity. Within four days, despite storage in liquid nitrogen, 75% of the binding activity and all of the adenylate cyclase activity in the solubilized preparation were lost. The factor(s) responsible for this lability remains unidentified.", "contents": "Characterization of the glucagon receptor in a pheochromocytoma. Glucagon activated adenylate cyclase in a homogenate of a pheochromocytoma over the concentration range 1 times 10 minus 8M to 1 times 10 minus 6M. Several other hormones including adrenocorticotropin, thyrotropin, parathyroid hormone and histamine were without effect. The tumor glucagon receptor was characterized and found to be similar in several ways to the glucagon receptor previously reported in normal tissue such as liver and heart. One, the receptor specifically bound 125-I-glucagon. Two, solubilization of the pheochromocytoma abolished glucagon-activation of the adenylate cyclase. Three, glucagon-responsiveness of the adenylate cyclase was partially restored by the addition of phosphatidylserine to the incubations. One major difference was observed between the glucagon receptor in tumor tissue and that in liver and heart, namely, a marked lability in 125-I-glucagon binding and adenylate cyclase activity. Within four days, despite storage in liquid nitrogen, 75% of the binding activity and all of the adenylate cyclase activity in the solubilized preparation were lost. The factor(s) responsible for this lability remains unidentified."} {"id": "PMID:165217", "title": "Measurement of the estradiol receptor in human breast tissue by the immobilized antibody method.", "content": "A simple immobilized antibody procedure for estradiol receptor detection has been applied to samples of human breast tissue cytosols previously assayed by the charcoal-dextran method. Good agreement between the two procedures was realized confirming the validity of the immobilized antibody assay.", "contents": "Measurement of the estradiol receptor in human breast tissue by the immobilized antibody method. A simple immobilized antibody procedure for estradiol receptor detection has been applied to samples of human breast tissue cytosols previously assayed by the charcoal-dextran method. Good agreement between the two procedures was realized confirming the validity of the immobilized antibody assay."} {"id": "PMID:165218", "title": "The effect of alpha-MSH on plasma growth hormone, cortisol and TSH in children.", "content": "The effect of synthetic alpha-MSH injected intravenously in a uniform dose of 3 mg was studied in 19 prepubertal children. A marked growth hormone (GH) response was seen only in 2 out of 8 constitutionally small children with a normal GH response to insulin and arginine stimulation. Three of of 11 children suffering from hypopituitarism with documented GH and other hormone deficiencies, unexpectedly, showed a significant rise of GH after alpha-MSH: all three had craniopharyngiomas. Alpha-MSH led to an increase of plasma cortisol in all except 3 patients who had secondary adrenal insuffciency. The increase of cortisol after alpha-MSH and after insulin was of the same extent: but the hypoglycemia and stress responsible for the insulin effect were not observed after alpha-MSH. It is possible that alpha-MSH acts by an ACTH-like direct stimulation on the adrenals. There was no effect of alpha-MSH on plasma TSH or on blood glucose.", "contents": "The effect of alpha-MSH on plasma growth hormone, cortisol and TSH in children. The effect of synthetic alpha-MSH injected intravenously in a uniform dose of 3 mg was studied in 19 prepubertal children. A marked growth hormone (GH) response was seen only in 2 out of 8 constitutionally small children with a normal GH response to insulin and arginine stimulation. Three of of 11 children suffering from hypopituitarism with documented GH and other hormone deficiencies, unexpectedly, showed a significant rise of GH after alpha-MSH: all three had craniopharyngiomas. Alpha-MSH led to an increase of plasma cortisol in all except 3 patients who had secondary adrenal insuffciency. The increase of cortisol after alpha-MSH and after insulin was of the same extent: but the hypoglycemia and stress responsible for the insulin effect were not observed after alpha-MSH. It is possible that alpha-MSH acts by an ACTH-like direct stimulation on the adrenals. There was no effect of alpha-MSH on plasma TSH or on blood glucose."} {"id": "PMID:165219", "title": "Relationships among the secretion of ACTH, GH, and cortisol during the insulin-induced hypoglycemia test in the normal and obese child.", "content": "The behavior of the secretion of ACTH, GH, and plasma cortisol during the insulin-induced hypoglycemia test on normal and obese children was studied. The secretion of the above-mentioned hormones was determined by calculating the integrals of the curves. The mean values of the integrals of the plasma cortisol and ACTH curves do not show any significant differences between the two groups of children. The mean values of the ratios between the integrals of the plasma cortisol and ACTH curves show a significant difference between the two groups (P smaller than 0.01). Since the mean values of the integrals of the plasma cortisol curves are practically the same in both groups, the difference in the above-mentioned ratios refers to the lower values of the integrals of the ACTH curves found in the obese children. This enables us to make the hypothesis that in the obese child the function of the pituitary-adrenal axis, at least during the insulin test, does not differ from the norm thanks to the adaptation of the ACTH secretion to the greater sensitivity of the adrenal glands to this hormone. In both the groups examined there was no correlation between the secretion of ACTH and plasma cortisol, between ACTH and GH, and between plasma cortisol and GH.", "contents": "Relationships among the secretion of ACTH, GH, and cortisol during the insulin-induced hypoglycemia test in the normal and obese child. The behavior of the secretion of ACTH, GH, and plasma cortisol during the insulin-induced hypoglycemia test on normal and obese children was studied. The secretion of the above-mentioned hormones was determined by calculating the integrals of the curves. The mean values of the integrals of the plasma cortisol and ACTH curves do not show any significant differences between the two groups of children. The mean values of the ratios between the integrals of the plasma cortisol and ACTH curves show a significant difference between the two groups (P smaller than 0.01). Since the mean values of the integrals of the plasma cortisol curves are practically the same in both groups, the difference in the above-mentioned ratios refers to the lower values of the integrals of the ACTH curves found in the obese children. This enables us to make the hypothesis that in the obese child the function of the pituitary-adrenal axis, at least during the insulin test, does not differ from the norm thanks to the adaptation of the ACTH secretion to the greater sensitivity of the adrenal glands to this hormone. In both the groups examined there was no correlation between the secretion of ACTH and plasma cortisol, between ACTH and GH, and between plasma cortisol and GH."} {"id": "PMID:165220", "title": "Plasma growth hormone and slow wave sleep increase after interruption of sleep.", "content": "A comparison was made of plasma hGH and of sleep stages during one night of undistrubed sleep and one night in which sleep was interupted by an hour of enforced wakefulness folowing the end of the second NREM-REM sleep cycle in 8 normal subjects. Plasma was sampled at 15-min intervals. HGH and slow wave sleep were both significantly increased in the two cycles immediately following the period awake compared with the same two cycles during nights of uninterruped sleep. The difference arose predominantly in the fourth cycle of the night, i.e., in the second cycle after the sleep interuption. The findings are consistent with the belief that extra wakefulness brings additional sleep of high RESTORATIVE properties.", "contents": "Plasma growth hormone and slow wave sleep increase after interruption of sleep. A comparison was made of plasma hGH and of sleep stages during one night of undistrubed sleep and one night in which sleep was interupted by an hour of enforced wakefulness folowing the end of the second NREM-REM sleep cycle in 8 normal subjects. Plasma was sampled at 15-min intervals. HGH and slow wave sleep were both significantly increased in the two cycles immediately following the period awake compared with the same two cycles during nights of uninterruped sleep. The difference arose predominantly in the fourth cycle of the night, i.e., in the second cycle after the sleep interuption. The findings are consistent with the belief that extra wakefulness brings additional sleep of high RESTORATIVE properties."} {"id": "PMID:165221", "title": "The effect of lergotrile on galactorrhea and gonadotropin secretion.", "content": "Lergotrile (Compound 83636), a specific inhibitor of prolactin release, was administered to 5 women with galactorrhea. Only 1 of the 5 had an elevated serum prolactin (hPRL) value, but Compound 83636 induced a decrease in serum hPRL in all cases. All patients had cessation of breast secretion within 72 days after initiation of lergotrile. LRH administration (100 pg) evoked a variable gonadotropin response before and during treatment with the ergot alkaloid. By contrast, serum prolactin values remained essentially unaltered after injection of LRH under the same conditions.", "contents": "The effect of lergotrile on galactorrhea and gonadotropin secretion. Lergotrile (Compound 83636), a specific inhibitor of prolactin release, was administered to 5 women with galactorrhea. Only 1 of the 5 had an elevated serum prolactin (hPRL) value, but Compound 83636 induced a decrease in serum hPRL in all cases. All patients had cessation of breast secretion within 72 days after initiation of lergotrile. LRH administration (100 pg) evoked a variable gonadotropin response before and during treatment with the ergot alkaloid. By contrast, serum prolactin values remained essentially unaltered after injection of LRH under the same conditions."} {"id": "PMID:165222", "title": "A specific, high-affinity, limited-capacity estrogen binding component in the cytosol of human fetal pituitary and brain tissues.", "content": "A macromoleclar component which binds 3H-estradiol with high affinity and limited capacity is present in the 150,000 x g supernatant fraction of pituitary, hypothalamus, cortex, and limbic system of both male and female human fetwses. 17 beta-estradiol and 17alpha-ethinylestradiol effectively compete with 3H-estradiol for binding sites while testosterone, dihydrotes-tosterone, and cortisol do not. The binding component is different from sexhormone-binding-globulin. It is present in these tissues in relatively large amounts and it is tentatively identified as an estrogen recptor.", "contents": "A specific, high-affinity, limited-capacity estrogen binding component in the cytosol of human fetal pituitary and brain tissues. A macromoleclar component which binds 3H-estradiol with high affinity and limited capacity is present in the 150,000 x g supernatant fraction of pituitary, hypothalamus, cortex, and limbic system of both male and female human fetwses. 17 beta-estradiol and 17alpha-ethinylestradiol effectively compete with 3H-estradiol for binding sites while testosterone, dihydrotes-tosterone, and cortisol do not. The binding component is different from sexhormone-binding-globulin. It is present in these tissues in relatively large amounts and it is tentatively identified as an estrogen recptor."} {"id": "PMID:165223", "title": "The effect of serotonin (5-hydroxytryptamine) and derivatives on guanosine 3',5'-monophosphate in human monocytes.", "content": "The effects of several putative mediators of inflammatory responses on the cyclic nucleotide content of mononuclear leukocytes from human peripheral blood were investigated. Incubation of mononuclear cells with 100 muM serotonin (a maximally effective concentration) for 5 min caused a five- to eightfold increase in their content of guanosine 3',5'-monophosphate (cAMP)...", "contents": "The effect of serotonin (5-hydroxytryptamine) and derivatives on guanosine 3',5'-monophosphate in human monocytes. The effects of several putative mediators of inflammatory responses on the cyclic nucleotide content of mononuclear leukocytes from human peripheral blood were investigated. Incubation of mononuclear cells with 100 muM serotonin (a maximally effective concentration) for 5 min caused a five- to eightfold increase in their content of guanosine 3',5'-monophosphate (cAMP)..."} {"id": "PMID:165226", "title": "Effect of adrenalectomy and insulin insufficiency upon the adenosine 3', 5' cyclic monophosphate system of the rat mammary glands.", "content": "Effects of adrenalectomy and acute insulin insufficiency upon tissue adenosine 3', 5' cyclic monophosphate concentrations, and adenyl cyclase, phosphodiesterase, and protein kinase activities were investigated. Adrenalectomy decreased intracellular adenosine 3', 5' cyclic monophosphate 53% and increased the activities of both adenylcyclase and phosphodiesterase. Cortisol therapy returned these to normal. During insulin insufficiency caused by anti-insulin serum, mammary adenosine 3', 5' cyclic monophosphate concentrations increased. The acute effects of insulin insufficiency and chronic effects of adrenelectomy suggest that insulin acts upon rat mammary glands to decrease and glucocorticoids, acting over longer term, to increase adenosine 3', 5' cyclic monophosphate concentrations.", "contents": "Effect of adrenalectomy and insulin insufficiency upon the adenosine 3', 5' cyclic monophosphate system of the rat mammary glands. Effects of adrenalectomy and acute insulin insufficiency upon tissue adenosine 3', 5' cyclic monophosphate concentrations, and adenyl cyclase, phosphodiesterase, and protein kinase activities were investigated. Adrenalectomy decreased intracellular adenosine 3', 5' cyclic monophosphate 53% and increased the activities of both adenylcyclase and phosphodiesterase. Cortisol therapy returned these to normal. During insulin insufficiency caused by anti-insulin serum, mammary adenosine 3', 5' cyclic monophosphate concentrations increased. The acute effects of insulin insufficiency and chronic effects of adrenelectomy suggest that insulin acts upon rat mammary glands to decrease and glucocorticoids, acting over longer term, to increase adenosine 3', 5' cyclic monophosphate concentrations."} {"id": "PMID:165231", "title": "Comparative ultrahistochemistry of the adepidermal granules of Salmo irideus, Lebistis reticulatus and Hynobiuo tokyoensis. Enzyme digestive experiment for the epoxy-embedded sections;.", "content": "A comparative ultrahistochemical investigation of the adepidermal granules of Salmo irideus, Lebistis reticulatus and Hynobius tokyoensis was carried out using enzyme digestion methods on epoxy-embedded sections. The granules of S. irideus larvae were decomposed by periodic acid, and digested by lipase without periodic acid pretreatmenetection of the granules. The secondary postosmificated granules were digested by lipase as in S; irideus, but complete decomposition by periodic acid was not observed in this experiment; Both periodic acid and lipase changed the shape of the adepidermal granules of H. tokyoensis to suggest partial digestion, but it appeared that these granules show rather stronger resistance to periodic acid and lipase than those of S. irideus. The granules of H. tokyoensis were completely digested when the sections were treated sequentially with phospholipase C, neuraminidase and lipase.", "contents": "Comparative ultrahistochemistry of the adepidermal granules of Salmo irideus, Lebistis reticulatus and Hynobiuo tokyoensis. Enzyme digestive experiment for the epoxy-embedded sections;. A comparative ultrahistochemical investigation of the adepidermal granules of Salmo irideus, Lebistis reticulatus and Hynobius tokyoensis was carried out using enzyme digestion methods on epoxy-embedded sections. The granules of S. irideus larvae were decomposed by periodic acid, and digested by lipase without periodic acid pretreatmenetection of the granules. The secondary postosmificated granules were digested by lipase as in S; irideus, but complete decomposition by periodic acid was not observed in this experiment; Both periodic acid and lipase changed the shape of the adepidermal granules of H. tokyoensis to suggest partial digestion, but it appeared that these granules show rather stronger resistance to periodic acid and lipase than those of S. irideus. The granules of H. tokyoensis were completely digested when the sections were treated sequentially with phospholipase C, neuraminidase and lipase."} {"id": "PMID:165233", "title": "Inhibition studies of alkaline phosphatase in hard tissue-forming cells.", "content": "The effects of the alkaline phosphatase inhibitors levamisole and R 8231 on p-nitro-phenylphosphatase, inorganic pyrophosphatase and adenosine triphosphatase (ATPase) activities in dentingenically active odontoblasts were studied. The p-nitrophenylphosphatase and inorganic pyrophosphatase activities were inhibited, while 40% of the ATP-splitting enzyme activity remained under the assay condition used. This finding, togeather with earlier studies, indicates that at least two different phosphatase are active at alkaline pH in hard tissue-forming cells; on nonspecific alkaline phosphatase and one specific ATPase. The ATPase activity is uninfluenced by ouabain and ruthenium red and is activated by Ca-2+ ions.", "contents": "Inhibition studies of alkaline phosphatase in hard tissue-forming cells. The effects of the alkaline phosphatase inhibitors levamisole and R 8231 on p-nitro-phenylphosphatase, inorganic pyrophosphatase and adenosine triphosphatase (ATPase) activities in dentingenically active odontoblasts were studied. The p-nitrophenylphosphatase and inorganic pyrophosphatase activities were inhibited, while 40% of the ATP-splitting enzyme activity remained under the assay condition used. This finding, togeather with earlier studies, indicates that at least two different phosphatase are active at alkaline pH in hard tissue-forming cells; on nonspecific alkaline phosphatase and one specific ATPase. The ATPase activity is uninfluenced by ouabain and ruthenium red and is activated by Ca-2+ ions."} {"id": "PMID:165234", "title": "Immunization interview survey in the Mongolian People's Republic.", "content": "An immunization interview survey was carried out in the urban and rural areas of Mongolia. The population sample interrogated comprised 1359 households with 6994 household members, 3634 of them younger than 15 years. The data collection unit was a private household, where information on administrative, demographic and socio-economic items was obtained in addition to detailed information on vaccination histories. A fair number of individuals with a positive history was found among children aged 1 to 5 years; the highest rates were determined among preschool and school-children aged 5 to 9. Significant differences in vaccination rates were found between urban and rural dwellers, urban areas displaying a higher proportion of vaccinated children in the younger age groups and rural areas among school-age children. A significantly higher proportion of vaccinated individuals was found among children living in somons than those living in aimac centres. No significant differences were found between children attending child collective institutions and those educated solely at home. The immunization interview survey was specially directed toward obtaining an estimate of the vaccinated population segment with reference to age in demarcated areas and thus detecting \"weak spots\" requiring remedial action.", "contents": "Immunization interview survey in the Mongolian People's Republic. An immunization interview survey was carried out in the urban and rural areas of Mongolia. The population sample interrogated comprised 1359 households with 6994 household members, 3634 of them younger than 15 years. The data collection unit was a private household, where information on administrative, demographic and socio-economic items was obtained in addition to detailed information on vaccination histories. A fair number of individuals with a positive history was found among children aged 1 to 5 years; the highest rates were determined among preschool and school-children aged 5 to 9. Significant differences in vaccination rates were found between urban and rural dwellers, urban areas displaying a higher proportion of vaccinated children in the younger age groups and rural areas among school-age children. A significantly higher proportion of vaccinated individuals was found among children living in somons than those living in aimac centres. No significant differences were found between children attending child collective institutions and those educated solely at home. The immunization interview survey was specially directed toward obtaining an estimate of the vaccinated population segment with reference to age in demarcated areas and thus detecting \"weak spots\" requiring remedial action."} {"id": "PMID:165235", "title": "Study of Pseudomonas haemolysin. II. Characteristics of Pseudomonas haemolysin.", "content": "Haemolysins of 4 strains of Pseudomonas aeruginosa producing different fractions [II, 2 + II, I + II + III] were studied. The production of specific antibodies was demonstrated making possible the immunoelectrophoretic record of the whole lysin and of the individual fractions. Tests on laboratory animals [mice, rabbits] showed a high degree lethal and dermonecrotic property of the lysin containing the fractions II + III and I + II + III.", "contents": "Study of Pseudomonas haemolysin. II. Characteristics of Pseudomonas haemolysin. Haemolysins of 4 strains of Pseudomonas aeruginosa producing different fractions [II, 2 + II, I + II + III] were studied. The production of specific antibodies was demonstrated making possible the immunoelectrophoretic record of the whole lysin and of the individual fractions. Tests on laboratory animals [mice, rabbits] showed a high degree lethal and dermonecrotic property of the lysin containing the fractions II + III and I + II + III."} {"id": "PMID:165236", "title": "Reproduction of vaccinia virus (strain neurolapina) in rabbit blood leucocytes in vitro.", "content": "The determining factor in vaccinia virus reproduction is the initial pattern and subsequent development of the given cell populations, in relation to the infection multiplicity, interferon production and other factors. The sensitive cells in fresh suspensions may be the blood monocytes and the small lymphocytes are virus-resistant. In cultures, transformed lymphocytes (blast cells) and macrophages play the major role in virus reproduction. The macrophages are probably of greater significance for the production of infectious virus. Replication of virus antigen was initiated in the polymorphonuclear cells in exceptional cases only, and only in the presence of a larger infection dose.", "contents": "Reproduction of vaccinia virus (strain neurolapina) in rabbit blood leucocytes in vitro. The determining factor in vaccinia virus reproduction is the initial pattern and subsequent development of the given cell populations, in relation to the infection multiplicity, interferon production and other factors. The sensitive cells in fresh suspensions may be the blood monocytes and the small lymphocytes are virus-resistant. In cultures, transformed lymphocytes (blast cells) and macrophages play the major role in virus reproduction. The macrophages are probably of greater significance for the production of infectious virus. Replication of virus antigen was initiated in the polymorphonuclear cells in exceptional cases only, and only in the presence of a larger infection dose."} {"id": "PMID:165237", "title": "Immunochemical and chemical studies on streptococcal group-specific carbohydrates.", "content": "Structural studies on the carbohydrates of Groups A, C, and A-variant (AV) streptococci have utilized periodate oxidation, permethylation analysis, and immunochemical comparison of intact and periodate-oxidized polysaccharides. The data indicate that a similar 1,2- and 1,3-linked rhamnose chain is present in both the A and AV carbohydrates. The group A carbohydrate contains in addition N-acetylglucosamine residues at nonreducing terminals, whereas the AV is a homopolymer of rhamnose. There is some evidence that Group Ccarbohydrate contains the same rhamnose chain, but structural comparisons to the A and AV carbohydrates are complicated by the presence of intrachain N-acetylgalactosamine residues. Periodate oxidation and permethylation analysis show that while approximately 50% of the N-acetylgalactosamine of the Group C carbohydrate occupies terminal positions, the remainder is present as 1,3-linked units. Removal of the nonreducing terminal hexosamine units from the Group A carbohydrate by periodate treatment significantly enhanced its cross-reactivity with AV antiserum, whereas no enhancement was observed after similar treatment of the Group C carbohydrate. The data indicate the presence of an alpha-1,3-linked N-acetylgalactosamine disaccharide at the nonreducing terminal of the Group C carbohydrate.", "contents": "Immunochemical and chemical studies on streptococcal group-specific carbohydrates. Structural studies on the carbohydrates of Groups A, C, and A-variant (AV) streptococci have utilized periodate oxidation, permethylation analysis, and immunochemical comparison of intact and periodate-oxidized polysaccharides. The data indicate that a similar 1,2- and 1,3-linked rhamnose chain is present in both the A and AV carbohydrates. The group A carbohydrate contains in addition N-acetylglucosamine residues at nonreducing terminals, whereas the AV is a homopolymer of rhamnose. There is some evidence that Group Ccarbohydrate contains the same rhamnose chain, but structural comparisons to the A and AV carbohydrates are complicated by the presence of intrachain N-acetylgalactosamine residues. Periodate oxidation and permethylation analysis show that while approximately 50% of the N-acetylgalactosamine of the Group C carbohydrate occupies terminal positions, the remainder is present as 1,3-linked units. Removal of the nonreducing terminal hexosamine units from the Group A carbohydrate by periodate treatment significantly enhanced its cross-reactivity with AV antiserum, whereas no enhancement was observed after similar treatment of the Group C carbohydrate. The data indicate the presence of an alpha-1,3-linked N-acetylgalactosamine disaccharide at the nonreducing terminal of the Group C carbohydrate."} {"id": "PMID:165238", "title": "Control of proliferation in mitogen responsive human peripheral blood lymphocytes: restimulation of cells stimulated by sodium periodate.", "content": "Human peripheral blood lymphocytes are stimulated to a greater extent by sodium periodate when cells are incubated in medium containing human serum than when incubated in medium with fetal calf serum. NaIO4 STIMULATION CAN BE REVERSED BY TREATMENT WITH SODIUM BOROHYDRIDE BUT CELLS ALREADY COMMITTED TO DIVISION ARE NOT AFFECTED BY BOROHYDRATE TREATMENT. Maximal commitment to DNA synthesis of a NaIO4 oxidized cell suspens-on occurs after about 28 hr of incubation in medium. The committal time after periodate stimulation is identical to that after stimulation with concanavalin A. Cells treated with periodate and then reduced with borohydride immediately after oxidation are refractory to further per-odate stimulation. Cells stimulated with periodate and then incubated for 6 hr before treatment with borohydride can be restimulated with periodate, indicating a turnover of membrane sites in the 6 hr period. Periodate-stimulated cells divide only once in response to the stimulation. The progeny of cells which were stimulated with periodate can be restimulated by treatment with either periodate or concanavalin A.", "contents": "Control of proliferation in mitogen responsive human peripheral blood lymphocytes: restimulation of cells stimulated by sodium periodate. Human peripheral blood lymphocytes are stimulated to a greater extent by sodium periodate when cells are incubated in medium containing human serum than when incubated in medium with fetal calf serum. NaIO4 STIMULATION CAN BE REVERSED BY TREATMENT WITH SODIUM BOROHYDRIDE BUT CELLS ALREADY COMMITTED TO DIVISION ARE NOT AFFECTED BY BOROHYDRATE TREATMENT. Maximal commitment to DNA synthesis of a NaIO4 oxidized cell suspens-on occurs after about 28 hr of incubation in medium. The committal time after periodate stimulation is identical to that after stimulation with concanavalin A. Cells treated with periodate and then reduced with borohydride immediately after oxidation are refractory to further per-odate stimulation. Cells stimulated with periodate and then incubated for 6 hr before treatment with borohydride can be restimulated with periodate, indicating a turnover of membrane sites in the 6 hr period. Periodate-stimulated cells divide only once in response to the stimulation. The progeny of cells which were stimulated with periodate can be restimulated by treatment with either periodate or concanavalin A."} {"id": "PMID:165239", "title": "The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli.", "content": "Heat-stable, chemotactically active peptides have been obtained from Escherichia coli culture filtrates. They range in size between 150 and 1500 daltons and are anionic at neutral pH. Free carboxyl groups but not free amino groups appear to be required for activity. The N-terminal group may be blocked. There do not appear to be internal aromatic or basic residues in the chemotactically active fractions. A highly purified, not completely characterized, fraction was found to contain aspartic acid, serine, glutamic acid, alanine, and glycine.", "contents": "The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli. Heat-stable, chemotactically active peptides have been obtained from Escherichia coli culture filtrates. They range in size between 150 and 1500 daltons and are anionic at neutral pH. Free carboxyl groups but not free amino groups appear to be required for activity. The N-terminal group may be blocked. There do not appear to be internal aromatic or basic residues in the chemotactically active fractions. A highly purified, not completely characterized, fraction was found to contain aspartic acid, serine, glutamic acid, alanine, and glycine."} {"id": "PMID:165241", "title": "Specific immunity and nonspecific resistance to infection: listeria, protozoa, and viruses in mice and hamsters,.", "content": "Specific immunity developed by mice against protozoan (Toxoplasma gondii and Besnoitia jellisoni) and bacterial (Listeria monocytogenes) infections was compared with nonspecific protection conferred by prior infections. The results indicated that homologous immunity protected mice from more than 10-5 LD50 of T. gondii or B. jellisoni, but from only 10-2 LD50 of L. monocytogenes. Heterospecific protection among these organisms was for 10-0.4 minus 10-1.2 LD50. In studies in hamsters specific immunity to protozoan (T. gondii and B. jellisoni) and viral (equine Herpesvirus type 1 and Oriboca virus) infections was compared with nonspecific protection conferred by prior infections with several heterospecific agents: T. gondii; B. jellison; equine Herpesvirus type 1; Oriboca, Ossa, vesicular stomatitis, yellow fever, and Newcastle disease viruses; L. monocytogenes; and the bacillus Calmette-Guerin strain of Mycobacterium tuberculosis. The results indicated that homologous immunity in hamsters was effective against 10-6 minus 10-7 LD50 of T. gondii, B. jellisoni, equine Herpesvirus type 1, or Oriboca virus. Prior infection with Newcastle disease virus protected (probably by interferon induction) against 10-3 LD50 of equine Herpesvirus type 1. Heterospecific protection among other agents was for less than 10 LD50. This insignificant heterospecific protection in infections in which cellular immunity plays a role suggests that both the induction phase and the expression phase are specific.", "contents": "Specific immunity and nonspecific resistance to infection: listeria, protozoa, and viruses in mice and hamsters,. Specific immunity developed by mice against protozoan (Toxoplasma gondii and Besnoitia jellisoni) and bacterial (Listeria monocytogenes) infections was compared with nonspecific protection conferred by prior infections. The results indicated that homologous immunity protected mice from more than 10-5 LD50 of T. gondii or B. jellisoni, but from only 10-2 LD50 of L. monocytogenes. Heterospecific protection among these organisms was for 10-0.4 minus 10-1.2 LD50. In studies in hamsters specific immunity to protozoan (T. gondii and B. jellisoni) and viral (equine Herpesvirus type 1 and Oriboca virus) infections was compared with nonspecific protection conferred by prior infections with several heterospecific agents: T. gondii; B. jellison; equine Herpesvirus type 1; Oriboca, Ossa, vesicular stomatitis, yellow fever, and Newcastle disease viruses; L. monocytogenes; and the bacillus Calmette-Guerin strain of Mycobacterium tuberculosis. The results indicated that homologous immunity in hamsters was effective against 10-6 minus 10-7 LD50 of T. gondii, B. jellisoni, equine Herpesvirus type 1, or Oriboca virus. Prior infection with Newcastle disease virus protected (probably by interferon induction) against 10-3 LD50 of equine Herpesvirus type 1. Heterospecific protection among other agents was for less than 10 LD50. This insignificant heterospecific protection in infections in which cellular immunity plays a role suggests that both the induction phase and the expression phase are specific."} {"id": "PMID:165242", "title": "Treatment of varicella-zoster virus infections with adenine arabinoside.", "content": "Twenty-three patients with complicated varicella-zoster virus infections were treated with adenine arabinoside. Of 14 patients with herpes zoster, 13 had malignancy treated with irradiation and cytotoxic agents or steroids. Although the duration of active vesicle formation in these patients ranged from two to 14 days before therapy, no new lesions appeared after the fourth day of treatment with adenine arabinoside. Zoster encephalitis developed in one patient on the third day of treatment, and severe postherpetic neuralgia was seen in three patients. Of nine treated patients with primary varicella, six improved, including five with evidence of varicella pneumonia. Two of the three patients with varicella who died were immunosuppressed and had progressive viral pneumonia with persistently high titers of virus in vesicular fluid; the third pateint was a child with Reye's syndrome. Double-blind controlled studies will be necessary to demonstrate the efficacy of adenine arabinoside in the treatment of infections with varicella-zoster virus.", "contents": "Treatment of varicella-zoster virus infections with adenine arabinoside. Twenty-three patients with complicated varicella-zoster virus infections were treated with adenine arabinoside. Of 14 patients with herpes zoster, 13 had malignancy treated with irradiation and cytotoxic agents or steroids. Although the duration of active vesicle formation in these patients ranged from two to 14 days before therapy, no new lesions appeared after the fourth day of treatment with adenine arabinoside. Zoster encephalitis developed in one patient on the third day of treatment, and severe postherpetic neuralgia was seen in three patients. Of nine treated patients with primary varicella, six improved, including five with evidence of varicella pneumonia. Two of the three patients with varicella who died were immunosuppressed and had progressive viral pneumonia with persistently high titers of virus in vesicular fluid; the third pateint was a child with Reye's syndrome. Double-blind controlled studies will be necessary to demonstrate the efficacy of adenine arabinoside in the treatment of infections with varicella-zoster virus."} {"id": "PMID:165243", "title": "Cellular events in zoster vesicles: relation to clinical course and immune parameters.", "content": "The cellular responses in zoster vesicles was studied chronologically in 30 patients, some of whom were compromised hosts with disseminated disease. Cell counts were low initially but rose abuptly later. Polymorphonuclear leukocytes predominated at all times in the vesicular fluid and in the cells adherent to the vesicle base. The abrupt rise in the number of cells generally coincided with an abrupt rise in the titer of vesicular interferon; both increases preceded resolution of local infection and cessation of cutaneous dissemination in disseminated disease, but the sequence of the increases was variable. The peak interferon titer correlated with cessation of dissemination better than did peak cell counts, and the timing of the local events contrasted with appearance of complement-fixing antibody, which commonly occurred after the resolution of disease. Possible interpretations are that a few sensitized lymphocytes may initiate the defensive response, produce interferon, and/or produce chemotactic factors that augment the polymorphonuclear response. The appearance of polymorphonuclear cells may be a nonspecific inflammatory response, or these cells or the deeper mononuclear infiltrate seen in biopsies may contribute to the rise in local interferon.", "contents": "Cellular events in zoster vesicles: relation to clinical course and immune parameters. The cellular responses in zoster vesicles was studied chronologically in 30 patients, some of whom were compromised hosts with disseminated disease. Cell counts were low initially but rose abuptly later. Polymorphonuclear leukocytes predominated at all times in the vesicular fluid and in the cells adherent to the vesicle base. The abrupt rise in the number of cells generally coincided with an abrupt rise in the titer of vesicular interferon; both increases preceded resolution of local infection and cessation of cutaneous dissemination in disseminated disease, but the sequence of the increases was variable. The peak interferon titer correlated with cessation of dissemination better than did peak cell counts, and the timing of the local events contrasted with appearance of complement-fixing antibody, which commonly occurred after the resolution of disease. Possible interpretations are that a few sensitized lymphocytes may initiate the defensive response, produce interferon, and/or produce chemotactic factors that augment the polymorphonuclear response. The appearance of polymorphonuclear cells may be a nonspecific inflammatory response, or these cells or the deeper mononuclear infiltrate seen in biopsies may contribute to the rise in local interferon."} {"id": "PMID:165244", "title": "Cervical cytomegalovirus excretion in pregnant and nonpregnant women: suppression in early gestation.", "content": "Comparison of 659 pregnant and 202 nonpregnant women with similar demographic characteristics showed overall rates of cervical cytomegalovirus excretion that were identical (9.5% vs. 9.4%) and were surprisingly high, especially since 89% of the pregnant group possessed antibody to cytomegalovirus when admitted to the study. Prevalence of cytomegalovirus among gravidas was significantly lower during the first (1.6%) than during the third (11.3%) trimester. Thus, early pregnancy appeared to exert a suppressive effect on viral excretion that waned with advancing gestation. A similar but less significant occurrence was observed in the two groups with respect to viuria. Increasing age also appeared to suppress the virologic expression of cervical and urinary tract infection, whereas multiparity seemingly produced such an effect only in the cervix. Among both cervical and urinary excreters, a few shed virus thoughout pregnancy, and others shed virus intermittently; however, viral shedding most commonly began in late gestation and frequently continued into the postpartum period. Primary infection was not documented, and antibody status remained unchanged with the advent of viral excretion in most cases. Thus, reactivation of endogenous virus seems the most likely explanation for viral shedding in our population. Similar rates of isolation of Neisseria gonorrhoeae in excreters and nonexcreters further argue against the other major possibility, venereal reinfection.", "contents": "Cervical cytomegalovirus excretion in pregnant and nonpregnant women: suppression in early gestation. Comparison of 659 pregnant and 202 nonpregnant women with similar demographic characteristics showed overall rates of cervical cytomegalovirus excretion that were identical (9.5% vs. 9.4%) and were surprisingly high, especially since 89% of the pregnant group possessed antibody to cytomegalovirus when admitted to the study. Prevalence of cytomegalovirus among gravidas was significantly lower during the first (1.6%) than during the third (11.3%) trimester. Thus, early pregnancy appeared to exert a suppressive effect on viral excretion that waned with advancing gestation. A similar but less significant occurrence was observed in the two groups with respect to viuria. Increasing age also appeared to suppress the virologic expression of cervical and urinary tract infection, whereas multiparity seemingly produced such an effect only in the cervix. Among both cervical and urinary excreters, a few shed virus thoughout pregnancy, and others shed virus intermittently; however, viral shedding most commonly began in late gestation and frequently continued into the postpartum period. Primary infection was not documented, and antibody status remained unchanged with the advent of viral excretion in most cases. Thus, reactivation of endogenous virus seems the most likely explanation for viral shedding in our population. Similar rates of isolation of Neisseria gonorrhoeae in excreters and nonexcreters further argue against the other major possibility, venereal reinfection."} {"id": "PMID:165245", "title": "Cellular immune responses to Herpes simplex virus type 1 in recurrent herpes labialis: in vitro blastogenesis and cytotoxicity to infected cell line.", "content": "Cellular immunity to herpes simplex virus type 1 (HSV-1) in 12 volunteers with recurrent herpes labialis was evaluated by means of two microassays. In the blastogenesis assay, lymphocytes were incubated with tissue culture cells persistently infected with HSV-1. Uninfected cells were used as controls, and a blastogenic index was calculated. The mean blastogenic index (plus or minus SD) for subjects with recurrent herpes labialis was 26.9 (plus or minus 8.3); the mean blastogenic index (plus or minus SD) in control donors with antibody to HSV-1 was 13.4 (plus or minus 7.2). The difference between these values was statistically significant (t equals 4.154; P smaller than 0.001). In the cytotoxicity assay, cells of the same persistently infected line were used as target cells, and release of 51-Cr from these cells or from control cells served as the index of lymphocyte reactivity. Specific immune release attributable to HSV-1 averages 3.7% (plus or minus 1.8%) in subjects with recurrent herpes labialis, compared with 23.1% (plus or minus 9.8%) in controls (t equals 6.135; P smaller than 0.001). These data suggest a dissociation between mechanisms of cellular immunity, with enhanced lymphocyte blastogenesis but decreased cytotoxicity. Recurrent herpes labialis may thus result from subtle cellular immune deficiency involving at least one of the efferent mechanisms.", "contents": "Cellular immune responses to Herpes simplex virus type 1 in recurrent herpes labialis: in vitro blastogenesis and cytotoxicity to infected cell line. Cellular immunity to herpes simplex virus type 1 (HSV-1) in 12 volunteers with recurrent herpes labialis was evaluated by means of two microassays. In the blastogenesis assay, lymphocytes were incubated with tissue culture cells persistently infected with HSV-1. Uninfected cells were used as controls, and a blastogenic index was calculated. The mean blastogenic index (plus or minus SD) for subjects with recurrent herpes labialis was 26.9 (plus or minus 8.3); the mean blastogenic index (plus or minus SD) in control donors with antibody to HSV-1 was 13.4 (plus or minus 7.2). The difference between these values was statistically significant (t equals 4.154; P smaller than 0.001). In the cytotoxicity assay, cells of the same persistently infected line were used as target cells, and release of 51-Cr from these cells or from control cells served as the index of lymphocyte reactivity. Specific immune release attributable to HSV-1 averages 3.7% (plus or minus 1.8%) in subjects with recurrent herpes labialis, compared with 23.1% (plus or minus 9.8%) in controls (t equals 6.135; P smaller than 0.001). These data suggest a dissociation between mechanisms of cellular immunity, with enhanced lymphocyte blastogenesis but decreased cytotoxicity. Recurrent herpes labialis may thus result from subtle cellular immune deficiency involving at least one of the efferent mechanisms."} {"id": "PMID:165246", "title": "Organ culture of human aorta: prolonged survival with support of viral replication.", "content": "Organ cultures were established with use of human fetal aorta obtained after death; cellular elements were preserved in the cultures for periods of up to eight weeks, with maintenance of their in vivo tissue relationships. Histologically, these cultures preserve the three coats of the aorta, including an intact endothelial layer cells. The aorta organ cultures supported the replication of echovirus 11, herpes simplex virus type 1, adenovirus 2, and coxsackievirus B5 without the production of detectable gross cytoarchitectural degenerative changes. Coxsackievirus B5 and adenovirus 2 were excreted by infected cultures for prolonged periods of up to 12 weeks. This human fetal aorta organ culture system, with its long-term viability and capacity to support viral replication, provides a useful model for in vitro study of virus-aortic vessel interactions.", "contents": "Organ culture of human aorta: prolonged survival with support of viral replication. Organ cultures were established with use of human fetal aorta obtained after death; cellular elements were preserved in the cultures for periods of up to eight weeks, with maintenance of their in vivo tissue relationships. Histologically, these cultures preserve the three coats of the aorta, including an intact endothelial layer cells. The aorta organ cultures supported the replication of echovirus 11, herpes simplex virus type 1, adenovirus 2, and coxsackievirus B5 without the production of detectable gross cytoarchitectural degenerative changes. Coxsackievirus B5 and adenovirus 2 were excreted by infected cultures for prolonged periods of up to 12 weeks. This human fetal aorta organ culture system, with its long-term viability and capacity to support viral replication, provides a useful model for in vitro study of virus-aortic vessel interactions."} {"id": "PMID:165247", "title": "Enterotoxins of Escherichia coli and vibriocholerae: tools for the molecular biologist.", "content": "With the independent discovery in several different laboratories that Vibrio cholerae and heat-labile Escherichia coli enterotoxins activated an enzyme (adenylate cyclase) in small intestinal epithealial cells to cause an enhanced intestinal secretion mediated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), a molecular mechanism was provided for these disease states. As agents that also elevate intracellular concentrations of cyclic AMP in virtually every mammalian tissue tested, the enterotoxins are potentially invaluable tools in investigation of the molecular sequence of events of all cyclic AMP-related cellular phenomena. Cyclic AMP has been known for some time to be the central regulator in the cellular expression of the effects of hormones and has become known more recently as an agent that controls cellular growth by corrdinately influencing several biochemical processes related to rate of cell division. Successful application of the enterotoxins as cellular probes in the areas of regulation of cell division, determination of the reaction mechanism of adenylate cyclase, and elucidation of the relationship between prostaglandin and adenylate cyclase, both in this laboratory and in those of others, is reviewed.", "contents": "Enterotoxins of Escherichia coli and vibriocholerae: tools for the molecular biologist. With the independent discovery in several different laboratories that Vibrio cholerae and heat-labile Escherichia coli enterotoxins activated an enzyme (adenylate cyclase) in small intestinal epithealial cells to cause an enhanced intestinal secretion mediated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), a molecular mechanism was provided for these disease states. As agents that also elevate intracellular concentrations of cyclic AMP in virtually every mammalian tissue tested, the enterotoxins are potentially invaluable tools in investigation of the molecular sequence of events of all cyclic AMP-related cellular phenomena. Cyclic AMP has been known for some time to be the central regulator in the cellular expression of the effects of hormones and has become known more recently as an agent that controls cellular growth by corrdinately influencing several biochemical processes related to rate of cell division. Successful application of the enterotoxins as cellular probes in the areas of regulation of cell division, determination of the reaction mechanism of adenylate cyclase, and elucidation of the relationship between prostaglandin and adenylate cyclase, both in this laboratory and in those of others, is reviewed."} {"id": "PMID:165250", "title": "Tumours of the parotid region.", "content": "Fifty-eight operatively treated tumours of the parotid region are presented. Of the tumours 85 per cent were benign and 15 per cent malignant. The percentage of pleomorphic adenomas was 36 per cent. During five years of observation there were no recurrences of benign tumours. Operative complications consisted of one paresis of the mandibular branch of the facial nerve and one death due to bleeding and aspiration during the first postoperative day. Frey's syndrome occurred postoperatively in 26 per cent of the cases. It is emphasized that parotid tumours should be concentrated to centres where surgeons have sufficient experience with these cases.", "contents": "Tumours of the parotid region. Fifty-eight operatively treated tumours of the parotid region are presented. Of the tumours 85 per cent were benign and 15 per cent malignant. The percentage of pleomorphic adenomas was 36 per cent. During five years of observation there were no recurrences of benign tumours. Operative complications consisted of one paresis of the mandibular branch of the facial nerve and one death due to bleeding and aspiration during the first postoperative day. Frey's syndrome occurred postoperatively in 26 per cent of the cases. It is emphasized that parotid tumours should be concentrated to centres where surgeons have sufficient experience with these cases."} {"id": "PMID:165251", "title": "Studies of rat liver microsomal diglyceride acyltransferase and cholinephosphotransferase using microsomal-bound substrate: effects of high fructose intake.", "content": "Radiolabeled phosphatidate and diglyceride were prepared bound to rat liver microsomes. These compounds were used as substrates in studies of diglyceride acyltransferase, cholinephosphotransferase, and CTP:phosphatidic acid cytidylyltransferase. Optimum incubation conditions for these reactions in microsomes from normal male rats are described. High fructose diets were fed to rats for 11 days; this resulted in an increased rate of neutral lipid formation from sn-glycerol-3-phosphate by liver microsomal preparations. This was attributed, in part, to a previously reported increase in liver phosphatidate phosphatase activity. The significance of this increase is supported by the finding of a fall in microsomal phosphatidate content and a doubling in microsomal diglyceride. In addition, diglyceride acyltransferase measured with microsomal-bound diglyceride was increased twofold with no equivalent change in cholinephosphotransferase activity. Such a change should result in preferential triglyceride formation from the increased microsomal diglyceride pool. CTP:phosphatidic acid cytidylytransferase activity was depressed by the high fructose diet. These combined alterations would lead to an accelerated hepatic triglyceride formation, a result found in vivo during high fructose feeding. The high fructose diet decreased slightly the total microsomal phospholipid content and markedly depressed phosphatidylethanolamine levels.", "contents": "Studies of rat liver microsomal diglyceride acyltransferase and cholinephosphotransferase using microsomal-bound substrate: effects of high fructose intake. Radiolabeled phosphatidate and diglyceride were prepared bound to rat liver microsomes. These compounds were used as substrates in studies of diglyceride acyltransferase, cholinephosphotransferase, and CTP:phosphatidic acid cytidylyltransferase. Optimum incubation conditions for these reactions in microsomes from normal male rats are described. High fructose diets were fed to rats for 11 days; this resulted in an increased rate of neutral lipid formation from sn-glycerol-3-phosphate by liver microsomal preparations. This was attributed, in part, to a previously reported increase in liver phosphatidate phosphatase activity. The significance of this increase is supported by the finding of a fall in microsomal phosphatidate content and a doubling in microsomal diglyceride. In addition, diglyceride acyltransferase measured with microsomal-bound diglyceride was increased twofold with no equivalent change in cholinephosphotransferase activity. Such a change should result in preferential triglyceride formation from the increased microsomal diglyceride pool. CTP:phosphatidic acid cytidylytransferase activity was depressed by the high fructose diet. These combined alterations would lead to an accelerated hepatic triglyceride formation, a result found in vivo during high fructose feeding. The high fructose diet decreased slightly the total microsomal phospholipid content and markedly depressed phosphatidylethanolamine levels."} {"id": "PMID:165252", "title": "Mechanism of avian estrogen-induced hypertriglyceridemia: evidence for overproduction of triglyceride.", "content": "Relying on methods other than the determination of turnover rate of triglyceride from the curve of plasma triglyceride radioactivity after administration of labeled precursor, we have confirmed that the endogenous hypertriglyceridemia induced by estrogenization of the chick is accompanied by increased production of triglyceride. Chicks estrogenized with diethylstilbestrol became grossly hypertriglyceridemic and had elevated levels of plasma free fatty acid. Within 5 min of administration of labeled palmitate, estrogenized hypertriglyceridemic birds converted approximately 10 times more plasma free fatty acid to hepatic triglyceride than did controls. In addition, 2 hr after intraperitoneal injection of [14-C]acetate or [U-14-C]glucose, the specific activity of very low density lipoprotein triglyceride (VLDL-TG) of estrogenized birds reached or exceeded that of the untreated controls, and the rapid enrichment of the vastly expanded plasma VLDL-TG pool with labeled triglyceride further indicated that increased production of triglyceride occurs with estrogenization. Furthermore, [14-C]acetate incorporation into VLDL-TG was calculated to be 1.6 and 6.6% of the injected dose in estrogenized birds compared with 0.1 and 0.2% in untreated birds. Increased production of plasma VLDL-TG was confirmed by a kinetic study of VLDL-TG metabolism, employing reinjected, endogenously prepared [14-C]triglyceride-labeled VLDL. The fractional turnover rate of VLDL-TG in estrogenized hypertriglyceridemic birds was substantially less than that in untreated controls (0.32 plus or minus 0.03 vs 0.71 plus or minus 0.03/hr), but the total turnover rate was nearly 50 times greater (244 plus or minus 52 vs. 5 plus or minus 1 mg/hr).", "contents": "Mechanism of avian estrogen-induced hypertriglyceridemia: evidence for overproduction of triglyceride. Relying on methods other than the determination of turnover rate of triglyceride from the curve of plasma triglyceride radioactivity after administration of labeled precursor, we have confirmed that the endogenous hypertriglyceridemia induced by estrogenization of the chick is accompanied by increased production of triglyceride. Chicks estrogenized with diethylstilbestrol became grossly hypertriglyceridemic and had elevated levels of plasma free fatty acid. Within 5 min of administration of labeled palmitate, estrogenized hypertriglyceridemic birds converted approximately 10 times more plasma free fatty acid to hepatic triglyceride than did controls. In addition, 2 hr after intraperitoneal injection of [14-C]acetate or [U-14-C]glucose, the specific activity of very low density lipoprotein triglyceride (VLDL-TG) of estrogenized birds reached or exceeded that of the untreated controls, and the rapid enrichment of the vastly expanded plasma VLDL-TG pool with labeled triglyceride further indicated that increased production of triglyceride occurs with estrogenization. Furthermore, [14-C]acetate incorporation into VLDL-TG was calculated to be 1.6 and 6.6% of the injected dose in estrogenized birds compared with 0.1 and 0.2% in untreated birds. Increased production of plasma VLDL-TG was confirmed by a kinetic study of VLDL-TG metabolism, employing reinjected, endogenously prepared [14-C]triglyceride-labeled VLDL. The fractional turnover rate of VLDL-TG in estrogenized hypertriglyceridemic birds was substantially less than that in untreated controls (0.32 plus or minus 0.03 vs 0.71 plus or minus 0.03/hr), but the total turnover rate was nearly 50 times greater (244 plus or minus 52 vs. 5 plus or minus 1 mg/hr)."} {"id": "PMID:165253", "title": "Lipid composition of plasma membranes from human leukemic lymphocytes.", "content": "The specific activity of adenosine 5'-monophosphatase and the concentrations of cholesterol, glucosylceramide, lactosylceramide, and phospholipids were compared in the whole homogenates and in plasma membrane fractions in four preparations of human leukemic lymphocytes taken over a 1-yr period from a patient with chronic lymphocytic leukemia. There was a 69.5-fold enrichment of the specific activity of adenosine 5'-monophosphatase in plasma membrane fractions. This enzyme appeared to be the best plasma membrane marker of all compounds studied. The increase in lactosylceramide concentration in the plasma membranes was 34.4-fold. It was significantly higher than that of glucosylceramide. The enrichment of glucosylceramide in the plasma membranes was similar to that of cholesterol and total phospholipids. The pattern of individual phospholipids in the plasma membrane fraction, as compared with the whole homogenate, was characterized by a decrease in phosphatidylcholine and an increase in sphingomyelin.", "contents": "Lipid composition of plasma membranes from human leukemic lymphocytes. The specific activity of adenosine 5'-monophosphatase and the concentrations of cholesterol, glucosylceramide, lactosylceramide, and phospholipids were compared in the whole homogenates and in plasma membrane fractions in four preparations of human leukemic lymphocytes taken over a 1-yr period from a patient with chronic lymphocytic leukemia. There was a 69.5-fold enrichment of the specific activity of adenosine 5'-monophosphatase in plasma membrane fractions. This enzyme appeared to be the best plasma membrane marker of all compounds studied. The increase in lactosylceramide concentration in the plasma membranes was 34.4-fold. It was significantly higher than that of glucosylceramide. The enrichment of glucosylceramide in the plasma membranes was similar to that of cholesterol and total phospholipids. The pattern of individual phospholipids in the plasma membrane fraction, as compared with the whole homogenate, was characterized by a decrease in phosphatidylcholine and an increase in sphingomyelin."} {"id": "PMID:165256", "title": "Correlation of early murine leukemia virus titer and H-2 type with spontaneous leukemia in mice of the BALB/c times AKR cross: a genetic analysis.", "content": "Tissue extracts from 6-wk old mice of the AKR strain (H-K) show high levels of infectious murine leukemia virus, and these mice show a near 100% incidence of spontaneous leukemia. In F1 mice of the cross, BALB/c times AKR (H-2K/H-2K), both the occurrence of virus and the incidence of spontaneous leukemia are suppressed to very low values, due largely to the presence of the FV-1b allele inherited from the BALB/c parent. Mice of the (BALB/c times AKR) F-1 times AKR backcross generation were observed for possible correlations between virus expressions at 6 wk of age, H-2 type and leukemia incidence. H-2 type showed at most a weak influence on the occurrence of infectious virus, but there was a very strong correlation between the level of virus expression and the occurrence of leukemia and a strong correlation between H-2 type and leukemia. In addition, there was a highly significant nonrandom distribution of virus-negative mice among the backcross litters, suggesting a maternal effect on virus expression.", "contents": "Correlation of early murine leukemia virus titer and H-2 type with spontaneous leukemia in mice of the BALB/c times AKR cross: a genetic analysis. Tissue extracts from 6-wk old mice of the AKR strain (H-K) show high levels of infectious murine leukemia virus, and these mice show a near 100% incidence of spontaneous leukemia. In F1 mice of the cross, BALB/c times AKR (H-2K/H-2K), both the occurrence of virus and the incidence of spontaneous leukemia are suppressed to very low values, due largely to the presence of the FV-1b allele inherited from the BALB/c parent. Mice of the (BALB/c times AKR) F-1 times AKR backcross generation were observed for possible correlations between virus expressions at 6 wk of age, H-2 type and leukemia incidence. H-2 type showed at most a weak influence on the occurrence of infectious virus, but there was a very strong correlation between the level of virus expression and the occurrence of leukemia and a strong correlation between H-2 type and leukemia. In addition, there was a highly significant nonrandom distribution of virus-negative mice among the backcross litters, suggesting a maternal effect on virus expression."} {"id": "PMID:165257", "title": "Separation of antigen-specific lymphocytes. II. Enrichment of hapten-specific antibody-forming cell precursors.", "content": "Normal spleen cells were separated in dishes coated with thin layers of DNP-gelatin or NIP-gelatin into binding and nonbinding cells and stimulated in vitro with DNP- and/or NIP-conjugated polymerized flagellin (POL). Hapten-specific unresponsiveness was induced in the binding cell population by melting the gel at 37 degrees C or in unfractionated cells by pretreatment with soluble hapten-gelatin and could be reversed by treatment with collagenase. A specific enrichment of anti-DNP and anti-NIP antibody-forming cell precursors (AFCP) could be demonstrated in the binding cell populations after treatment with collagenase in cultures with or without \"feeder\" cells. However, the response of small numbers of unfractionated and purified hapten-specific spleen cells was suboptimal even in the presence of mitomycin-treated or irradiated feeder cells. Optimal numbers of anti-DNP (anti-NIP) antibody-forming cells were generated by small numbers of normal or purified spleen cells in the presence of spleen cells depleted of anti-DNP (anti-NIP) AFCP. In this system the response of only 2 times 10-4 purified hapten-specific cells was higher than the response of 10-6 unfractionated cells. Purified DNP-specific cells responded only to DNP-POL but not to NIP-POL and purified NIP-specific cells responded only to NIP-POL but not to DNP-POL. The degree of enrichment of anti-DNP AFCP decreased with increasing numbers of binding cells. NIP3-gelatin layers bound four to five times less spleen cells than DNP2-gelatin layers and the enrichment of anti-NIP AFCP (about 300-fold) was three times greater than the enrichment of anti-DNP AFCP (about 100-fold). The immunological significance of hapten-gelatin binding cells which apparently failed to respond to antigen is discussed.", "contents": "Separation of antigen-specific lymphocytes. II. Enrichment of hapten-specific antibody-forming cell precursors. Normal spleen cells were separated in dishes coated with thin layers of DNP-gelatin or NIP-gelatin into binding and nonbinding cells and stimulated in vitro with DNP- and/or NIP-conjugated polymerized flagellin (POL). Hapten-specific unresponsiveness was induced in the binding cell population by melting the gel at 37 degrees C or in unfractionated cells by pretreatment with soluble hapten-gelatin and could be reversed by treatment with collagenase. A specific enrichment of anti-DNP and anti-NIP antibody-forming cell precursors (AFCP) could be demonstrated in the binding cell populations after treatment with collagenase in cultures with or without \"feeder\" cells. However, the response of small numbers of unfractionated and purified hapten-specific spleen cells was suboptimal even in the presence of mitomycin-treated or irradiated feeder cells. Optimal numbers of anti-DNP (anti-NIP) antibody-forming cells were generated by small numbers of normal or purified spleen cells in the presence of spleen cells depleted of anti-DNP (anti-NIP) AFCP. In this system the response of only 2 times 10-4 purified hapten-specific cells was higher than the response of 10-6 unfractionated cells. Purified DNP-specific cells responded only to DNP-POL but not to NIP-POL and purified NIP-specific cells responded only to NIP-POL but not to DNP-POL. The degree of enrichment of anti-DNP AFCP decreased with increasing numbers of binding cells. NIP3-gelatin layers bound four to five times less spleen cells than DNP2-gelatin layers and the enrichment of anti-NIP AFCP (about 300-fold) was three times greater than the enrichment of anti-DNP AFCP (about 100-fold). The immunological significance of hapten-gelatin binding cells which apparently failed to respond to antigen is discussed."} {"id": "PMID:165258", "title": "Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system.", "content": "A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells.", "contents": "Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells."} {"id": "PMID:165259", "title": "Dissociation between mitogenicity and immunogenicity of TNP-lipopolysaccharide, a T-independent antigen.", "content": "Two models have been proposed to explain triggering of B cells by so-called \"T-independent antigen.\" Feldmann and Basten (1) proposed that the interaction of multiple repeating determinants on polymeric antigens with specific Ig receptors on the B-cell surface is sufficient to provide the signals for division of these cells and differentiation to antibody-forming cells. In contrast, coutinho et al. (2, and see review, 3) have claimed that there is only one signal, a mitogenic signal, receptors acting merely as passive focusing devices to localize the antigen on specific cells where it delivers a mitogenic signal resulting in differentiation to an antibody-producing cell. This model rests primarily on the demonstration that at high concentration all T-independent antigens they have tested are mitogenic for B cells (4-6). Compatible with this hypothesis are the observations that hydrolysis of lipopolysaccharide (LPS) to remove the ester- linked fatty acids of the mitogenic lipid A component abrogates its mitogenic (7,8) activity as well as its ability, when substituted with the TNP hapten, to induce a T-independent anti- TNP response (9). However, alkali treatment of LPS, although not changing its antigenic component (8), may also modify the molecule physically or chemically which could account for loss of immunogenic properties (10). We therefore investigated other reagents which interact with LPS in a more chemically defined manner in an effort to clarify the relationship between the mitogenic and immunogenic properties of this molecule. Polymyxin B (PB) is one of a family of cyclic peptide antibiotics which are bactericidal for most gram-negative bacteria. It prevents the lethal endotoxic activity of LPS (11, 12) and changes the physical structure of LPS (13). We report here that low doses of PB added to cultures of mouse spleen cells inhibit the mitogenic activity of TNP-LPS, a T- independent antigen, and native LPS, but do not suppress the immune response to TNP-LPS. PB interacts with TNP-LPS and LPS causing a physical change in the molecule. In addition, polymyxin-treated LPS is no longer mitogenic. These results suggest a dissociation between the mitogenic and immunogenic properties of TNP-LPS.", "contents": "Dissociation between mitogenicity and immunogenicity of TNP-lipopolysaccharide, a T-independent antigen. Two models have been proposed to explain triggering of B cells by so-called \"T-independent antigen.\" Feldmann and Basten (1) proposed that the interaction of multiple repeating determinants on polymeric antigens with specific Ig receptors on the B-cell surface is sufficient to provide the signals for division of these cells and differentiation to antibody-forming cells. In contrast, coutinho et al. (2, and see review, 3) have claimed that there is only one signal, a mitogenic signal, receptors acting merely as passive focusing devices to localize the antigen on specific cells where it delivers a mitogenic signal resulting in differentiation to an antibody-producing cell. This model rests primarily on the demonstration that at high concentration all T-independent antigens they have tested are mitogenic for B cells (4-6). Compatible with this hypothesis are the observations that hydrolysis of lipopolysaccharide (LPS) to remove the ester- linked fatty acids of the mitogenic lipid A component abrogates its mitogenic (7,8) activity as well as its ability, when substituted with the TNP hapten, to induce a T-independent anti- TNP response (9). However, alkali treatment of LPS, although not changing its antigenic component (8), may also modify the molecule physically or chemically which could account for loss of immunogenic properties (10). We therefore investigated other reagents which interact with LPS in a more chemically defined manner in an effort to clarify the relationship between the mitogenic and immunogenic properties of this molecule. Polymyxin B (PB) is one of a family of cyclic peptide antibiotics which are bactericidal for most gram-negative bacteria. It prevents the lethal endotoxic activity of LPS (11, 12) and changes the physical structure of LPS (13). We report here that low doses of PB added to cultures of mouse spleen cells inhibit the mitogenic activity of TNP-LPS, a T- independent antigen, and native LPS, but do not suppress the immune response to TNP-LPS. PB interacts with TNP-LPS and LPS causing a physical change in the molecule. In addition, polymyxin-treated LPS is no longer mitogenic. These results suggest a dissociation between the mitogenic and immunogenic properties of TNP-LPS."} {"id": "PMID:165268", "title": "Control by Preynaptic Correlation: a mechanism affecting information transmission from Ia fibers to motoneurons.", "content": "1. In the unanesthetized spinal cord of the cat, simultaneous intracellular recordings were made from two motoneurons belonging to the gastronemius motor nucleus. 2. Supramaximal iterative stimulation of small branches of the gastrocnemius nerve produced monosynaptic EPSPs (Ia EPSPs) of varying amplitude superimposed on a fluctuating base line. 3. In most cases the variance of the motoneuron membrane potential was increased above base-line levels with a time course approximately matching the Ia EPSP. This suggests that Ia EPSP fluctuations are greater than can be accounted for by the base-line fluctuations alone. 4. For a given series of Ia EPSPs, the smaller responses in the series had about the same decay phase as the larger EPSPs, suggesting that most of the Ia EPSP fluctuations were not due to systematic changes in postsynaptic conductances produced by ongoing activity, but rather to a presynaptic mechanism. 5. Simultaneous recording from two motoneurons showed that base-line fluctuations were positively correlated. In most cases, however, there was an additional increased correlation above base-line levels resembling the time course of the Ia EPSPs, indicating positive correlation between EPSP fluctuations which is attributed to a presynaptic mechanism. 6. Conditioning volleys to group I muscle afferents or to low-threshold cutaneous afferents reduced the variance of the Ia EPSPs and also their correlation in motoneuron pairs, often without changing the mean Ia EPSPs. 7. It is concluded that, in the unanesthetized spinal cord, in addition to the random process which governs transmitter release intrinsic to a given synaptic terminal, there is another stochastic process affecting, in a correlated manner, transmitter release in large sets of Ia synaptic terminals. Most likely, the correlation in transmitter release is achieved by membrane potential fluctuations imposed on the Ia terminal arborizations by ongoing activity of the segmental mechanism mediating primary afferent depolarization. 8. The effects of such a correlating influence on cell firing behavior have been analyzed. The results suggest that this mechanism, referred to as control by presynaptic correlation, is able to modulate the information transmitted from Ia fibers to motoneurons.", "contents": "Control by Preynaptic Correlation: a mechanism affecting information transmission from Ia fibers to motoneurons. 1. In the unanesthetized spinal cord of the cat, simultaneous intracellular recordings were made from two motoneurons belonging to the gastronemius motor nucleus. 2. Supramaximal iterative stimulation of small branches of the gastrocnemius nerve produced monosynaptic EPSPs (Ia EPSPs) of varying amplitude superimposed on a fluctuating base line. 3. In most cases the variance of the motoneuron membrane potential was increased above base-line levels with a time course approximately matching the Ia EPSP. This suggests that Ia EPSP fluctuations are greater than can be accounted for by the base-line fluctuations alone. 4. For a given series of Ia EPSPs, the smaller responses in the series had about the same decay phase as the larger EPSPs, suggesting that most of the Ia EPSP fluctuations were not due to systematic changes in postsynaptic conductances produced by ongoing activity, but rather to a presynaptic mechanism. 5. Simultaneous recording from two motoneurons showed that base-line fluctuations were positively correlated. In most cases, however, there was an additional increased correlation above base-line levels resembling the time course of the Ia EPSPs, indicating positive correlation between EPSP fluctuations which is attributed to a presynaptic mechanism. 6. Conditioning volleys to group I muscle afferents or to low-threshold cutaneous afferents reduced the variance of the Ia EPSPs and also their correlation in motoneuron pairs, often without changing the mean Ia EPSPs. 7. It is concluded that, in the unanesthetized spinal cord, in addition to the random process which governs transmitter release intrinsic to a given synaptic terminal, there is another stochastic process affecting, in a correlated manner, transmitter release in large sets of Ia synaptic terminals. Most likely, the correlation in transmitter release is achieved by membrane potential fluctuations imposed on the Ia terminal arborizations by ongoing activity of the segmental mechanism mediating primary afferent depolarization. 8. The effects of such a correlating influence on cell firing behavior have been analyzed. The results suggest that this mechanism, referred to as control by presynaptic correlation, is able to modulate the information transmitted from Ia fibers to motoneurons."} {"id": "PMID:165269", "title": "Receptive fields of cerebellar cells receiving exteroceptive input in a Gymnotid fish.", "content": "Single neurons in the caudal lobe of the cerebellum of the weakly electric fish Apteronotus albifrons respond to distortions in the normal electric field produced by the animal. Moving plastic or metal objects as well as a simpler stimulus, a moving electrical dipole, produce adequate distortions of the fish's field to cause the cerebellar cells to respond. The moving dipole stimulated small enough areas of the fish's skin, as determined by the responses of single electroreceptors, to allow maps of the receptive fields of single cerebellar cells to be produced. The receptive fields seen varied widely in complexity from relatively small excitatory or inhibitory areas to larger fields containing multiple excitatory and inhibitory areas usually bordering one another. Most cells studied displayed directional responses. Usually qualitatively different responses resulted from opposite directions of movement, and less frequently units were seen in which no response resulted from movement opposite the direction which caused responses; Varying the rate of stimulus movement caused only small changes in the responses of cerebellar cells; however, motionless stimuli applied over areas of skin known to respond to moving stimuli produced weaker responses of the appropriate sign for that area. Movement seems to be an important component of the stimulus for these cells. Cells were also seen which responded to visual as well as to electroreceptive input. Responses to each of these two modalities presented above were quite different. The cells recorded from frequently displayed burst discharges similar to those produced by Purkinje cells in other lower vertebrates, and most of the cells studied are believed to be Purkinje cells. A somatotopic relationship was found between the position of the center of a receptive field on the fish's body and the position of the cell in the brain. All of the results obtained are compatible with the hypothesis that the caudal lobe of the cerebellum is processing electroreceptive information related to object detection.", "contents": "Receptive fields of cerebellar cells receiving exteroceptive input in a Gymnotid fish. Single neurons in the caudal lobe of the cerebellum of the weakly electric fish Apteronotus albifrons respond to distortions in the normal electric field produced by the animal. Moving plastic or metal objects as well as a simpler stimulus, a moving electrical dipole, produce adequate distortions of the fish's field to cause the cerebellar cells to respond. The moving dipole stimulated small enough areas of the fish's skin, as determined by the responses of single electroreceptors, to allow maps of the receptive fields of single cerebellar cells to be produced. The receptive fields seen varied widely in complexity from relatively small excitatory or inhibitory areas to larger fields containing multiple excitatory and inhibitory areas usually bordering one another. Most cells studied displayed directional responses. Usually qualitatively different responses resulted from opposite directions of movement, and less frequently units were seen in which no response resulted from movement opposite the direction which caused responses; Varying the rate of stimulus movement caused only small changes in the responses of cerebellar cells; however, motionless stimuli applied over areas of skin known to respond to moving stimuli produced weaker responses of the appropriate sign for that area. Movement seems to be an important component of the stimulus for these cells. Cells were also seen which responded to visual as well as to electroreceptive input. Responses to each of these two modalities presented above were quite different. The cells recorded from frequently displayed burst discharges similar to those produced by Purkinje cells in other lower vertebrates, and most of the cells studied are believed to be Purkinje cells. A somatotopic relationship was found between the position of the center of a receptive field on the fish's body and the position of the cell in the brain. All of the results obtained are compatible with the hypothesis that the caudal lobe of the cerebellum is processing electroreceptive information related to object detection."} {"id": "PMID:165270", "title": "Analysis of postural motoneuron activity in crayfish abdomen. I. Coordination by premotoneuron connections.", "content": "The activity of the crayfish abdominal postural motoneurons and their associated neurons (the accessory neuron(s) and the MRO(1)) were examined with the aid of techniques for the analysis of simultaneously recorded spike trains. A means of reliably identifying the spikes of the individual motoneurons based on their relative axon conduction velocities is presented. The analyses show that: 1) the large, phasically active synergist motoneurons innervating muscles producing the same movement show a marked similarity in their average responses, which is independent of the input source; 2) the small, tonically active and the middle-sized, tonicphasic synergist motoneurons innervating the same muscle and similar synergist motoneurons innervating antagonistic muscles are coordinated entirely by premotoneuron connections; 3) the accessory neuron is coordinated in its activity with the phasically active flexor excitor motoneurons and the extensor inhibitor motoneuron and thereby functions as a flexor synergist; and 4) the simultaneous presentation of flexion-producing and extension-producing inputs to the postural system results in a reciprocal oscillation in flexor-extensor motoneuron output. The functional significance of these results with respect to the operation of the postural system are discussed.", "contents": "Analysis of postural motoneuron activity in crayfish abdomen. I. Coordination by premotoneuron connections. The activity of the crayfish abdominal postural motoneurons and their associated neurons (the accessory neuron(s) and the MRO(1)) were examined with the aid of techniques for the analysis of simultaneously recorded spike trains. A means of reliably identifying the spikes of the individual motoneurons based on their relative axon conduction velocities is presented. The analyses show that: 1) the large, phasically active synergist motoneurons innervating muscles producing the same movement show a marked similarity in their average responses, which is independent of the input source; 2) the small, tonically active and the middle-sized, tonicphasic synergist motoneurons innervating the same muscle and similar synergist motoneurons innervating antagonistic muscles are coordinated entirely by premotoneuron connections; 3) the accessory neuron is coordinated in its activity with the phasically active flexor excitor motoneurons and the extensor inhibitor motoneuron and thereby functions as a flexor synergist; and 4) the simultaneous presentation of flexion-producing and extension-producing inputs to the postural system results in a reciprocal oscillation in flexor-extensor motoneuron output. The functional significance of these results with respect to the operation of the postural system are discussed."} {"id": "PMID:165271", "title": "Analysis of postural motoneuron activity in crayfish abdomen. II. Coordination by excitatory and inhibitory connections between motoneurons.", "content": "The identified spike trains of the crayfish abdominal postural efferent neurons were recorded simultaneously from one or more segments. The efferent activity was analyzed using cross-correlation histograms, peristimulus time scatter diagrams, and specialized antidromic techniques. The analyses show that the larger, phasically active motoneurons are coordinated in their activity by cross connections made at the motoneuron level. The cross connections are both excitatory and inhibitor in nature and result in significant alterations in spike output. Further, the accessory neuron receives an inhibitory cross connection from a middle-sized extensor excitor motoneuron or motoneurons. In each case, the cross connections appear to be appropriate to the function of the postural system.", "contents": "Analysis of postural motoneuron activity in crayfish abdomen. II. Coordination by excitatory and inhibitory connections between motoneurons. The identified spike trains of the crayfish abdominal postural efferent neurons were recorded simultaneously from one or more segments. The efferent activity was analyzed using cross-correlation histograms, peristimulus time scatter diagrams, and specialized antidromic techniques. The analyses show that the larger, phasically active motoneurons are coordinated in their activity by cross connections made at the motoneuron level. The cross connections are both excitatory and inhibitor in nature and result in significant alterations in spike output. Further, the accessory neuron receives an inhibitory cross connection from a middle-sized extensor excitor motoneuron or motoneurons. In each case, the cross connections appear to be appropriate to the function of the postural system."} {"id": "PMID:165272", "title": "Experimental optimization of current source-density technique for anuran cerebellum.", "content": "This paper represents a systematic, semirigorous attempt to optimize the technique of current source-density (CSD) analysis experimentally. We compared different spatial differentiation formulas in terms of accuracy, aliasing, and smoothing, and provide experimental and theoretical rationale for their use. Sources of error have also been investigated. Expressions were derived to enable one to estimate the relative magnitude of errors due to electrical noise, uncertainty in tip position of recording electrodes, and error in the conductivity tensor. Corresponding experiments illlustrating the validity of such estimates are also presented. Methods to determine the optimum interelectrode spacing are given, based on computations of spatial energy-density spectra in the anuran cerebellum. The application of the technique of CSD analysis developed in this, and the accompanying paper, to the vestibulocerebellar input in the toad cerebellum provided significantly better temporal and spatial resolution of neuronal events than conventional field-potential analysis. Considerations germane to the optimum application of this technique to other neural structures are also discussed.", "contents": "Experimental optimization of current source-density technique for anuran cerebellum. This paper represents a systematic, semirigorous attempt to optimize the technique of current source-density (CSD) analysis experimentally. We compared different spatial differentiation formulas in terms of accuracy, aliasing, and smoothing, and provide experimental and theoretical rationale for their use. Sources of error have also been investigated. Expressions were derived to enable one to estimate the relative magnitude of errors due to electrical noise, uncertainty in tip position of recording electrodes, and error in the conductivity tensor. Corresponding experiments illlustrating the validity of such estimates are also presented. Methods to determine the optimum interelectrode spacing are given, based on computations of spatial energy-density spectra in the anuran cerebellum. The application of the technique of CSD analysis developed in this, and the accompanying paper, to the vestibulocerebellar input in the toad cerebellum provided significantly better temporal and spatial resolution of neuronal events than conventional field-potential analysis. Considerations germane to the optimum application of this technique to other neural structures are also discussed."} {"id": "PMID:165273", "title": "NADH fluorescence and [K+]o changes during hippocampal electrical stimulation.", "content": "1. Short (2 s) trains of stimuli were applied to the dorsal hippocampal surface of cats, producing an increase in [K+]o and a decrease in NADH fluorescence (the latter being indicative of an increase in tissue oxygen utilization). 2. The [K+]o rose rapidly during stimulation (delta[K+]o values from 1 to 6 mM) with larger stimulus currents producing larger changes. The time course of the poststimulus decline of [K+]o was an exponential decay function, with T 1/2 values varying from 1.3 to 6.9s, and independent of the magnitude of the delta[K+]o. Consistent undershoots of [K+]o occurred following stimuli causing less than 1 mM change in [K+]o. 3. The maximum depression of fluorescence and the time integral of the fluorescence changes following each stimulus train were both highly correlated with the total increase of [K+]o occurring during the stimulus train. 4. Application of several stimulus trains in close succession resulted in more rapid potassium reuptake following the later trains and an unusually large undershoot after the last train. Concomitantly, there was a progressive decrease in the fluorescence level. 5. When afterdischarges were induced by prolonged (less than 2 s) stimulation, larger and more sustained increases in [K+]o and decreases of fluorescence were observed, and there was some indication that afterdischarges were followed by accelerated reuptake of extracellular potassium.", "contents": "NADH fluorescence and [K+]o changes during hippocampal electrical stimulation. 1. Short (2 s) trains of stimuli were applied to the dorsal hippocampal surface of cats, producing an increase in [K+]o and a decrease in NADH fluorescence (the latter being indicative of an increase in tissue oxygen utilization). 2. The [K+]o rose rapidly during stimulation (delta[K+]o values from 1 to 6 mM) with larger stimulus currents producing larger changes. The time course of the poststimulus decline of [K+]o was an exponential decay function, with T 1/2 values varying from 1.3 to 6.9s, and independent of the magnitude of the delta[K+]o. Consistent undershoots of [K+]o occurred following stimuli causing less than 1 mM change in [K+]o. 3. The maximum depression of fluorescence and the time integral of the fluorescence changes following each stimulus train were both highly correlated with the total increase of [K+]o occurring during the stimulus train. 4. Application of several stimulus trains in close succession resulted in more rapid potassium reuptake following the later trains and an unusually large undershoot after the last train. Concomitantly, there was a progressive decrease in the fluorescence level. 5. When afterdischarges were induced by prolonged (less than 2 s) stimulation, larger and more sustained increases in [K+]o and decreases of fluorescence were observed, and there was some indication that afterdischarges were followed by accelerated reuptake of extracellular potassium."} {"id": "PMID:165274", "title": "Vestibular nystagmus and teleost oculomotor neurons: functions of electrotonic coupling and dendritic impulse initiation.", "content": "1. Nystagmus in the horizontal plane is evoked in fish by mechanical stimulation of the ampulla of the horizontal semicircular canal or by electrical stimulation of the nerve from this canal. The movements are conjugate and the slow phase is away from the side of stimulation. 2. Medial rectus motoneurons were recorded from intracellularly, during nystagmus. During the slow phase (induced by ipsilateral stimulation), impulses arise abruptly from the base line and appear to arise at a distance from the cell body. During the fast phase (evoked by contralateral stimulation), impulses appear to arise from large PSPs that must be generated at or near the cell body. 3. In the curarized fish, stimulation of the nerve from the contralateral horizontal canal evokes spikes that arise from large EPSPs and that are blocked relatively easily by hyperpolarizing currents. Stimulation of the nerve from the ipsilateral horizontal canal evokes spikes that arise abruptly from the base line and that are much more difficult to block by hyperpolarizing currents. Little if any underlying PSP is observed when these impulses are delayed or blocked. Thus impulses evoked by stimulation of contralateral and ipsilateral side are initiated near to and far from the cell soma, respectively. 4. If impulses evoked by contralateral stimulation fail to excite the cell body due to injury, antidromic spikes are not occluded. Thus contralateral stimulation initiates impulses in the dendrites. 5. Cell bodies of neighboring motoneurons are coupled electrotonically, and graded antidromic stimulation evokes graded depolarizing potentials which result from electrotonic spread of spike activity from adjacent neurons. These depolarizing potentials are adequate to excite the cells in the presence of a background EPSP evoked by contralateral canal stimulation. In this manner coupling tends to synchronize cells during the fast phase of the nystagmus. 6. Antidromic responses of neighboring cells fail to interact with dendritic inputs to a particular cell, although indirect evidence indicates antidromic spikes invade the impulse-initiating regions in the dendrites. Thus coupling between dendrites is negligible and dendritic inputs can mediate the smoothly graded movements of the slow nystagmic phase. Coupling between somata is too weak to cause significant interaction between dendritically evoked impulses (unless the cell bodies are depolarized by EPSPs). 7. Rhythmic firing can be recorded in a single presynaptic fiber corresponding to either the slow or the fast phase of nystagmus, but not to both. Oculomotor neurons appear to be \"relay cells\" that, during the fast phase of the nystagmus receive a synchronized synaptic input which is initiated in a higher level command nucleus.", "contents": "Vestibular nystagmus and teleost oculomotor neurons: functions of electrotonic coupling and dendritic impulse initiation. 1. Nystagmus in the horizontal plane is evoked in fish by mechanical stimulation of the ampulla of the horizontal semicircular canal or by electrical stimulation of the nerve from this canal. The movements are conjugate and the slow phase is away from the side of stimulation. 2. Medial rectus motoneurons were recorded from intracellularly, during nystagmus. During the slow phase (induced by ipsilateral stimulation), impulses arise abruptly from the base line and appear to arise at a distance from the cell body. During the fast phase (evoked by contralateral stimulation), impulses appear to arise from large PSPs that must be generated at or near the cell body. 3. In the curarized fish, stimulation of the nerve from the contralateral horizontal canal evokes spikes that arise from large EPSPs and that are blocked relatively easily by hyperpolarizing currents. Stimulation of the nerve from the ipsilateral horizontal canal evokes spikes that arise abruptly from the base line and that are much more difficult to block by hyperpolarizing currents. Little if any underlying PSP is observed when these impulses are delayed or blocked. Thus impulses evoked by stimulation of contralateral and ipsilateral side are initiated near to and far from the cell soma, respectively. 4. If impulses evoked by contralateral stimulation fail to excite the cell body due to injury, antidromic spikes are not occluded. Thus contralateral stimulation initiates impulses in the dendrites. 5. Cell bodies of neighboring motoneurons are coupled electrotonically, and graded antidromic stimulation evokes graded depolarizing potentials which result from electrotonic spread of spike activity from adjacent neurons. These depolarizing potentials are adequate to excite the cells in the presence of a background EPSP evoked by contralateral canal stimulation. In this manner coupling tends to synchronize cells during the fast phase of the nystagmus. 6. Antidromic responses of neighboring cells fail to interact with dendritic inputs to a particular cell, although indirect evidence indicates antidromic spikes invade the impulse-initiating regions in the dendrites. Thus coupling between dendrites is negligible and dendritic inputs can mediate the smoothly graded movements of the slow nystagmic phase. Coupling between somata is too weak to cause significant interaction between dendritically evoked impulses (unless the cell bodies are depolarized by EPSPs). 7. Rhythmic firing can be recorded in a single presynaptic fiber corresponding to either the slow or the fast phase of nystagmus, but not to both. Oculomotor neurons appear to be \"relay cells\" that, during the fast phase of the nystagmus receive a synchronized synaptic input which is initiated in a higher level command nucleus."} {"id": "PMID:165275", "title": "Effect of exercise on tissue lipids and serum lipoproteins of rats fed two levels of fat.", "content": "Adult rats were fed a low fat (4%) or a high fat (40%) diet, and groups of other rats selected for good running were fed these two diets and were treadmill exercised 5 days a week for 6 weeks. The serum triglycerides were significantly lower in exercised rats fed the low fat diet, but not in those fed the high fat diet, as compared with corresponding controls. The liver lipids were vastly elevated in sedentary rats fed the high fat diet as compared with those fed the low fat diet. An interesting effect of exercise was reflected by the near normal liver lipid levels in rats fed the high fat diet and exercised. However, in these animals, the muscle concentration of cholesterol was significantly higher than that in all other groups. The very low density lipoproteins tended to be lower while the low density lipoproteins tended to be greater in exercised as compared with sedentary rats. It was suggested that the decline in very low density lipoproteins was due to decreased synthesis resulting from adaptive changes in the exercised animal. It was further postulated that the increase in low density lipoproteins was possibly due to increased synthesis necessitated by the need to enhance the catabolism and excretion of cholesterol in exercised animals.", "contents": "Effect of exercise on tissue lipids and serum lipoproteins of rats fed two levels of fat. Adult rats were fed a low fat (4%) or a high fat (40%) diet, and groups of other rats selected for good running were fed these two diets and were treadmill exercised 5 days a week for 6 weeks. The serum triglycerides were significantly lower in exercised rats fed the low fat diet, but not in those fed the high fat diet, as compared with corresponding controls. The liver lipids were vastly elevated in sedentary rats fed the high fat diet as compared with those fed the low fat diet. An interesting effect of exercise was reflected by the near normal liver lipid levels in rats fed the high fat diet and exercised. However, in these animals, the muscle concentration of cholesterol was significantly higher than that in all other groups. The very low density lipoproteins tended to be lower while the low density lipoproteins tended to be greater in exercised as compared with sedentary rats. It was suggested that the decline in very low density lipoproteins was due to decreased synthesis resulting from adaptive changes in the exercised animal. It was further postulated that the increase in low density lipoproteins was possibly due to increased synthesis necessitated by the need to enhance the catabolism and excretion of cholesterol in exercised animals."} {"id": "PMID:165276", "title": "Vitamin E deficiency in the rat. Cytoplasmic factors required for suppression of mitochondrial respiratory decline.", "content": "Liver cytoplasm from either vitamin E-deficient or normal rats has been shown to suppress mitochondrial respiratory decline induced by microsomes in vitro. The present study is an attempt to identify cytoplasmic factor(s) responsible for this suppression. The effect of cytoplasm from both groups of animals could be removed by trichloroacetate precipitation, boiling, and dialysis against 0.3 M mannitol-o.1 mM Tris buffer, pH 7.4, but not by aging or extraction with isooctane. The addition of oxalacetate of alpha-ketoglutarate plus asparate to cytolplasm potentiated the suppressant effect. Dialyzed cytoplasm was not effective in depressing the respiratory decline. However, the addition of NAD, osalacetate, or alpha-ketoglutarate plus aspartate to dialyzed cytoplasm restored its ability to depress the respiratory decline. When oxalacetate or alpha-ketoglutarate plus aspartate was added to fresh cytoplasm, followed by dialysis, the effect of these compounds was not seen. These results suggest that cytoplasmic factor(s) required for suppression of the respiratory decline were enzymes of the malate shuttle and transamination, which are heat labile and trichloroacetate precipitable, plus the dialyzable metabolites that are associated with these enzymes in the generation of NAD in mitochondria.", "contents": "Vitamin E deficiency in the rat. Cytoplasmic factors required for suppression of mitochondrial respiratory decline. Liver cytoplasm from either vitamin E-deficient or normal rats has been shown to suppress mitochondrial respiratory decline induced by microsomes in vitro. The present study is an attempt to identify cytoplasmic factor(s) responsible for this suppression. The effect of cytoplasm from both groups of animals could be removed by trichloroacetate precipitation, boiling, and dialysis against 0.3 M mannitol-o.1 mM Tris buffer, pH 7.4, but not by aging or extraction with isooctane. The addition of oxalacetate of alpha-ketoglutarate plus asparate to cytolplasm potentiated the suppressant effect. Dialyzed cytoplasm was not effective in depressing the respiratory decline. However, the addition of NAD, osalacetate, or alpha-ketoglutarate plus aspartate to dialyzed cytoplasm restored its ability to depress the respiratory decline. When oxalacetate or alpha-ketoglutarate plus aspartate was added to fresh cytoplasm, followed by dialysis, the effect of these compounds was not seen. These results suggest that cytoplasmic factor(s) required for suppression of the respiratory decline were enzymes of the malate shuttle and transamination, which are heat labile and trichloroacetate precipitable, plus the dialyzable metabolites that are associated with these enzymes in the generation of NAD in mitochondria."} {"id": "PMID:165277", "title": "Tall girls: a survey of 15 years of management and treatment.", "content": "In the past 15 years 450 girls have been seen because of concern about tall stature: 168 of them have been treated with stilbestrol to control the growth rate. Of the latter group 87 have been followed after treatment for a sufficiently long time to be sure growth had ceased and to provide the data for this report. At the onset of treatment the following data (mean values) were recorded: chronologic age, 13.0 years; skeletal age, 13.2 years; height, 172.9 cm; estimated mature height 180.2 cm; and growth potential, 7.3 cm. At the end of treatment data of interest (mean values) were: reduction in final height, 3.5 cm; duration of therapy, 2.1 years; amount of stilbestrol given, 2.3 gm; age of last visit, 17.6 years. Side effects were minimal, though two girls developed parovarian cysts that required surgery during treatment. Not included in the series of 87, one additional girl was seen with a serous cystadenoma of the ovary, and one girl developed superficial venous thrombosis of the calf. Long-term follow-up has revealed no late complications. It is concluded that estrogen can reduce significantly the growth rate of almost all tall girls, but treatment must be carried out under very careful supervision, bearing in mind possible side effects.", "contents": "Tall girls: a survey of 15 years of management and treatment. In the past 15 years 450 girls have been seen because of concern about tall stature: 168 of them have been treated with stilbestrol to control the growth rate. Of the latter group 87 have been followed after treatment for a sufficiently long time to be sure growth had ceased and to provide the data for this report. At the onset of treatment the following data (mean values) were recorded: chronologic age, 13.0 years; skeletal age, 13.2 years; height, 172.9 cm; estimated mature height 180.2 cm; and growth potential, 7.3 cm. At the end of treatment data of interest (mean values) were: reduction in final height, 3.5 cm; duration of therapy, 2.1 years; amount of stilbestrol given, 2.3 gm; age of last visit, 17.6 years. Side effects were minimal, though two girls developed parovarian cysts that required surgery during treatment. Not included in the series of 87, one additional girl was seen with a serous cystadenoma of the ovary, and one girl developed superficial venous thrombosis of the calf. Long-term follow-up has revealed no late complications. It is concluded that estrogen can reduce significantly the growth rate of almost all tall girls, but treatment must be carried out under very careful supervision, bearing in mind possible side effects."} {"id": "PMID:165279", "title": "Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia.", "content": "Patients previously described with cartilage-hair hypoplasia, a distinctive form of short-limbed dwarfism, have been found to have deficient cell-mediated immunity with intact antibody-mediated immunity. The patient with cartilage-hair hypoplasia described in the present report is unusual in that she had both deficient antibody-mediated immunity and deficient cell-mediated immunity. In addition, she developed severe, vaccine-related paralytic poliomyelitis. This complication suggests that live viral vaccines should not be administered to children with short-limbed dwarfism until the form of short-limbed dwarfism is established and immunologic evaluation is performed when indicated.", "contents": "Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia. Patients previously described with cartilage-hair hypoplasia, a distinctive form of short-limbed dwarfism, have been found to have deficient cell-mediated immunity with intact antibody-mediated immunity. The patient with cartilage-hair hypoplasia described in the present report is unusual in that she had both deficient antibody-mediated immunity and deficient cell-mediated immunity. In addition, she developed severe, vaccine-related paralytic poliomyelitis. This complication suggests that live viral vaccines should not be administered to children with short-limbed dwarfism until the form of short-limbed dwarfism is established and immunologic evaluation is performed when indicated."} {"id": "PMID:165280", "title": "Erythrocyte membrane alterations induced by Plasmodium simium infection in Saimiri sciureus: relation to Sch\u00fcffner's dots.", "content": "The nature of erythrocyte membrane alterations in Plasmodium simium infections was determined employing light microscopy, carbon replication and transmission electron microscopy. Light microscopy of Giemsa stained preparations shows that infected cells initially acquire a faint stippling (schuffnerization) which becomes pronouced with subsequent parasite development. Enlargement of the host cell usually accompanied stippling. Both phenomena appear to depend on host cell age since infected mature erythrocytes were neither stippled nor enlarged. Carbon replicas show numerous indentations over the outer membrane surface of most infected cells. Their distribution suggests that they account for Schuffner's granules. The surface indentations are manifest as small infundibular which open to the infected cell's surface. Cytoplasmic microvesciles in the infected cell's stroma frequently are observed adjacent or catenated to the surface infundibula. Images suggest their funsion with the surface infundibula thus adding membrane to the cell's surface and accounting for host cell enlargement.", "contents": "Erythrocyte membrane alterations induced by Plasmodium simium infection in Saimiri sciureus: relation to Sch\u00fcffner's dots. The nature of erythrocyte membrane alterations in Plasmodium simium infections was determined employing light microscopy, carbon replication and transmission electron microscopy. Light microscopy of Giemsa stained preparations shows that infected cells initially acquire a faint stippling (schuffnerization) which becomes pronouced with subsequent parasite development. Enlargement of the host cell usually accompanied stippling. Both phenomena appear to depend on host cell age since infected mature erythrocytes were neither stippled nor enlarged. Carbon replicas show numerous indentations over the outer membrane surface of most infected cells. Their distribution suggests that they account for Schuffner's granules. The surface indentations are manifest as small infundibular which open to the infected cell's surface. Cytoplasmic microvesciles in the infected cell's stroma frequently are observed adjacent or catenated to the surface infundibula. Images suggest their funsion with the surface infundibula thus adding membrane to the cell's surface and accounting for host cell enlargement."} {"id": "PMID:165281", "title": "Reduction of blue tetrazolium by corticosteroids.", "content": "Pseudo-first-order rate constants were observed for the reaction of corticosteroid or corticosteroid esters with blue tetrazolium. The data indicate that the reactivity of corticosteroids is, in part, a function of their geometry in that corticosteroid reactivity toward blue tetrazolium increases with increasing planarity of the steroid molecule and that corticosteroid esters must be hydrolyzed as a necessary prerequisite to reaction with blue tetrazolium. Evidence is presented indicating that free radicals are not involved in the blue tetrazoliun reaction with corticosteroids. Certain pharmaceutically important compounds such as pyrocatechol derivatives and hydroquinone appear to reduce blue tetrazolium by the anion free radical mechanism proposed previously. A spectrophotometric method for determining the number of reduction units transferred to blue tetrazolium per molecule is described.", "contents": "Reduction of blue tetrazolium by corticosteroids. Pseudo-first-order rate constants were observed for the reaction of corticosteroid or corticosteroid esters with blue tetrazolium. The data indicate that the reactivity of corticosteroids is, in part, a function of their geometry in that corticosteroid reactivity toward blue tetrazolium increases with increasing planarity of the steroid molecule and that corticosteroid esters must be hydrolyzed as a necessary prerequisite to reaction with blue tetrazolium. Evidence is presented indicating that free radicals are not involved in the blue tetrazoliun reaction with corticosteroids. Certain pharmaceutically important compounds such as pyrocatechol derivatives and hydroquinone appear to reduce blue tetrazolium by the anion free radical mechanism proposed previously. A spectrophotometric method for determining the number of reduction units transferred to blue tetrazolium per molecule is described."} {"id": "PMID:165282", "title": "Cycloalkanones V: synthesis, distribution, and effects on triglyceride metabolism.", "content": "The 14-C-labeled 2,8-dibenzylcyclooctanone was synthesized to study its absorption, distribution, and excretion in rats. Maximum drug absorption from the GI tract occurred between 12 and 14 hr after administration. The major organs possessed maximum amounts of the drug in 1 hr, with the liver concentrating the most with 6.56% 14-C and the muscle mass reaching a maximum of 41% 14-C after 14 hr. The drug remained in the GI tract over the first 6 hr and was associated with the lipid and glycogen fractions. Eighty-seven percent was eliminated in the feces after 72 hr. 2,8-Dibenzylcyclooctanone caused a significant reduction in vitro of dihydroxyacetone phosphatase acyltransferase and sn-glycerol-3-phosphate acyltransferase, which is the proposed mechanism for the observed in vivo reduction of hepatic, intestinal, and serum triglycerides and total glycerolipids. In vivo administration of the drug resulted in a depression of liver acid phosphatidyl phosphatase, acid phosphatase and lipase, and adipose lipase. The drug increased the rates of excretion of exogenous cholesterol, palmitic acid, and progesterone.", "contents": "Cycloalkanones V: synthesis, distribution, and effects on triglyceride metabolism. The 14-C-labeled 2,8-dibenzylcyclooctanone was synthesized to study its absorption, distribution, and excretion in rats. Maximum drug absorption from the GI tract occurred between 12 and 14 hr after administration. The major organs possessed maximum amounts of the drug in 1 hr, with the liver concentrating the most with 6.56% 14-C and the muscle mass reaching a maximum of 41% 14-C after 14 hr. The drug remained in the GI tract over the first 6 hr and was associated with the lipid and glycogen fractions. Eighty-seven percent was eliminated in the feces after 72 hr. 2,8-Dibenzylcyclooctanone caused a significant reduction in vitro of dihydroxyacetone phosphatase acyltransferase and sn-glycerol-3-phosphate acyltransferase, which is the proposed mechanism for the observed in vivo reduction of hepatic, intestinal, and serum triglycerides and total glycerolipids. In vivo administration of the drug resulted in a depression of liver acid phosphatidyl phosphatase, acid phosphatase and lipase, and adipose lipase. The drug increased the rates of excretion of exogenous cholesterol, palmitic acid, and progesterone."} {"id": "PMID:165283", "title": "Effects of activity in single sensory fibres on the discharge patterns of dorsal spinocerebellar tract cells.", "content": "1. Electrical activity of dorsal spinocerebellar tract (DSCT) was recorded extracellularly and intracellularly in Clarke's column nucleus. 2.Trains of impluses were elicited in DSCT cells by static stretch of the hind limb muscles, and the distributions of intervals between the impulses were computed. These distributions were essentially similar before and after impalement of the cells with the micropipette, suggesting that cell injury caused by penetration was insignificant. 3. Patterns of synaptic activity revealed that the DSCT cells examined were innervated by a limited number of muscle afferents. 4. In some DSCT neurons, all excitatory post-synaptic potentials (e.p.s.p.s) elicited by a single fibre were suprathreshold, and e.p.s.p.s elicited by other afferents were usually subthreshold. These neurons discharge very regularly during muscle stretch, and the spike initiation followed nearly one-to-one relation in response to activity of the sensory fibre eliciting suprathreshold e.p.s.p.s. 5. The discharge pattern was irregular in other DSCT cells. In these cases, single sensory fibres evoked e.p.s.p.s. which did not always reach the firing threshold because of random fluctuation in their amplitude. 6. DSCT neurons often show low frequency discharges (about 10/sec) in the absence of sensory activation. In these conditions only small e.p.s.p.s. were detected (average, 0.53 mV) suggesting that the average membrane potential is very close (1-i mV) to the firing threshold. 7. It is concluded that the statistical properties of firing patterns in DSCT neurons activated by muscle afferents depend on (a) the large amplitude of e.p.s.p.s., (b) their firing threshold and (c) random fluctuations in the e.p.s.p.s. amplitude.", "contents": "Effects of activity in single sensory fibres on the discharge patterns of dorsal spinocerebellar tract cells. 1. Electrical activity of dorsal spinocerebellar tract (DSCT) was recorded extracellularly and intracellularly in Clarke's column nucleus. 2.Trains of impluses were elicited in DSCT cells by static stretch of the hind limb muscles, and the distributions of intervals between the impulses were computed. These distributions were essentially similar before and after impalement of the cells with the micropipette, suggesting that cell injury caused by penetration was insignificant. 3. Patterns of synaptic activity revealed that the DSCT cells examined were innervated by a limited number of muscle afferents. 4. In some DSCT neurons, all excitatory post-synaptic potentials (e.p.s.p.s) elicited by a single fibre were suprathreshold, and e.p.s.p.s elicited by other afferents were usually subthreshold. These neurons discharge very regularly during muscle stretch, and the spike initiation followed nearly one-to-one relation in response to activity of the sensory fibre eliciting suprathreshold e.p.s.p.s. 5. The discharge pattern was irregular in other DSCT cells. In these cases, single sensory fibres evoked e.p.s.p.s. which did not always reach the firing threshold because of random fluctuation in their amplitude. 6. DSCT neurons often show low frequency discharges (about 10/sec) in the absence of sensory activation. In these conditions only small e.p.s.p.s. were detected (average, 0.53 mV) suggesting that the average membrane potential is very close (1-i mV) to the firing threshold. 7. It is concluded that the statistical properties of firing patterns in DSCT neurons activated by muscle afferents depend on (a) the large amplitude of e.p.s.p.s., (b) their firing threshold and (c) random fluctuations in the e.p.s.p.s. amplitude."} {"id": "PMID:165284", "title": "Depression and recovery of transmission at the squid giant synapse.", "content": "1. The process of synaptic depression and recovery were studied in the squid (Loligo pealii) giant synapse with intracellular recording and stimulating electrodes in the prescence of tetrodotoxin (10-minus 7 M). 2. When the synapse was stimulated at 50 Hz, depression occurred rapidly. Recovery after the tetanus was a first-order process with an average recovery time constant of 4-9 sec. The rate of recovery was independent of the amplitude of the post-synaptic potential (p.s.p.) or the degree of depression. 3. For the first five to seven p.s.p.s in the train there was a linear relationship between depression and the total amount of transmitter previously released. This may indicate that depression in this preparation was caused by the depletion of the presynaptic store of transmitter (S). 4. Assuming that this interpretation was correct, we could show that recovery from depression during the tetanus (i.e. 'mobilization') proceeded about 10 times faster than after the end of the tetanus. 5. When the amplitude of the p.s.p. was varied by changing the bathing calcium concentration, [Ca], the degree of depression was correlated to the amplitude of the p.s.p. 6. When the amplitude of the p.s.p. was increased by increasing pre-synaptic depolarization, synaptic depression was found to increase as well. However, synaptic depression increased less than the amplitude of the p.s.p., the relationship between these two measures being non-linear. 7. This finding is interpreted to indicate that the transmitter stores, S, are closely related to the area of the presynaptic membrane which is sufficiently depolarized to release transmitter.", "contents": "Depression and recovery of transmission at the squid giant synapse. 1. The process of synaptic depression and recovery were studied in the squid (Loligo pealii) giant synapse with intracellular recording and stimulating electrodes in the prescence of tetrodotoxin (10-minus 7 M). 2. When the synapse was stimulated at 50 Hz, depression occurred rapidly. Recovery after the tetanus was a first-order process with an average recovery time constant of 4-9 sec. The rate of recovery was independent of the amplitude of the post-synaptic potential (p.s.p.) or the degree of depression. 3. For the first five to seven p.s.p.s in the train there was a linear relationship between depression and the total amount of transmitter previously released. This may indicate that depression in this preparation was caused by the depletion of the presynaptic store of transmitter (S). 4. Assuming that this interpretation was correct, we could show that recovery from depression during the tetanus (i.e. 'mobilization') proceeded about 10 times faster than after the end of the tetanus. 5. When the amplitude of the p.s.p. was varied by changing the bathing calcium concentration, [Ca], the degree of depression was correlated to the amplitude of the p.s.p. 6. When the amplitude of the p.s.p. was increased by increasing pre-synaptic depolarization, synaptic depression was found to increase as well. However, synaptic depression increased less than the amplitude of the p.s.p., the relationship between these two measures being non-linear. 7. This finding is interpreted to indicate that the transmitter stores, S, are closely related to the area of the presynaptic membrane which is sufficiently depolarized to release transmitter."} {"id": "PMID:165285", "title": "A dual effect of repetitive stimulation on post-tetanic potentiation of transmitter release at the frog neuromuscular junction.", "content": "1. End-plate potentials (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation(potentiation). 2. Potentiation is found to decay exponentially over most of its time course. 3. The time constant tsu(H) characterizing this exponential decay is a function of the previous history (frequency and duration) of stimulation. For example, tsu(H) increased from about 20 sec following a few impulses to over 70 sec following more than 1000 impulses. 4. A new method is presented to obtain estimates of the rise of potentiation (uncontaminated by facilitation or an intermediate facilitatory process) during repetitive stimulation. It is found that potentiation is present following short trains of impulses and continually increases in magnitude with the duration of the conditioning stimulation. Potentiation was at a maximum immediately following the conditioning trains. 5. The relationship between P(T), the magnitude of potentiation immediately following repetitive stimulation, and tsu(H), the time constant for the decay of this potentiation, is given by tsu(H)=Ae-P(T)/B, where A=19-8 plus or minus 5-1 sec (mean plus or minus S.D. of an observation) and B increases from 2.2plus or minus 2-1 to 5-7 plus or minus 2-7 as the stimulation rate increases from 5 to 30/sec. 6. The value of A in the above equation can be considered to represent the minimal time constant for the decay of potentiation--that is, the time constant for decay after a simgle impulse. 7. Evidence is presented for a afacilitatory process with a time constant of decay of about 3 sec which is intermediate in duration between facilitation and potentiation. 8. It is suggested that repetitive stimulation has a dual effect on potentiation; each impulse (1) adds an increment of potentiation and (2) increases tsu(H), the time constant for the decay of potentiation.", "contents": "A dual effect of repetitive stimulation on post-tetanic potentiation of transmitter release at the frog neuromuscular junction. 1. End-plate potentials (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation(potentiation). 2. Potentiation is found to decay exponentially over most of its time course. 3. The time constant tsu(H) characterizing this exponential decay is a function of the previous history (frequency and duration) of stimulation. For example, tsu(H) increased from about 20 sec following a few impulses to over 70 sec following more than 1000 impulses. 4. A new method is presented to obtain estimates of the rise of potentiation (uncontaminated by facilitation or an intermediate facilitatory process) during repetitive stimulation. It is found that potentiation is present following short trains of impulses and continually increases in magnitude with the duration of the conditioning stimulation. Potentiation was at a maximum immediately following the conditioning trains. 5. The relationship between P(T), the magnitude of potentiation immediately following repetitive stimulation, and tsu(H), the time constant for the decay of this potentiation, is given by tsu(H)=Ae-P(T)/B, where A=19-8 plus or minus 5-1 sec (mean plus or minus S.D. of an observation) and B increases from 2.2plus or minus 2-1 to 5-7 plus or minus 2-7 as the stimulation rate increases from 5 to 30/sec. 6. The value of A in the above equation can be considered to represent the minimal time constant for the decay of potentiation--that is, the time constant for decay after a simgle impulse. 7. Evidence is presented for a afacilitatory process with a time constant of decay of about 3 sec which is intermediate in duration between facilitation and potentiation. 8. It is suggested that repetitive stimulation has a dual effect on potentiation; each impulse (1) adds an increment of potentiation and (2) increases tsu(H), the time constant for the decay of potentiation."} {"id": "PMID:165286", "title": "A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction.", "content": "1. End-plate potential (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation (potentiation). 2. The magnitude of potentiation was not directly related to the number of conditioning impulses, but was a function of the frequency and duration of the conditioning stimulation. 3. Potentiation was always greater following an equal number of impulses delivered at a higher frequency of stimulation. 4. Plots of the magnitude of potentiation against the number of conditioning impulses would sometimes show an upward inflexion depending on the parameters of stimulation. 5. These experimental observations were described by a model based on the assumption (1) that potentiation is linearly related to a residual substance, R(t), which accumulates in the nerve terminal during repetitive stimulation, and (2) that each nerve impulse adds an identical increment, r, of this residual substance. The data were not described by assuming a 4th power relationship between potentiation and R(t). 6. The upward inflexion in potentiation (see paragraph 4) is described by the model as resulting from an increase in the time constant for the decay of potentiation as the magnitude of potentiation increases. 7. The increment of residual substance r added by each impulse was independent of the amount of transmitter released during the conditioning train. This increment typically increased transmitter release by amount 1% of the control level in the absence of potentiation. 8. Suggestions are given to explain why potentiation of transmitter release, which is thought to arise from an accumulation of Ca-2+ in the nerve terminal, can be described assuming a linear relationship between potentiation and R(t), the proposed substance responsible for potentiation, under experimental conditions in which a 3rd to 4th power relationship would be expected to exist between external Ca concentration and evoked transmitter release.", "contents": "A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction. 1. End-plate potential (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation (potentiation). 2. The magnitude of potentiation was not directly related to the number of conditioning impulses, but was a function of the frequency and duration of the conditioning stimulation. 3. Potentiation was always greater following an equal number of impulses delivered at a higher frequency of stimulation. 4. Plots of the magnitude of potentiation against the number of conditioning impulses would sometimes show an upward inflexion depending on the parameters of stimulation. 5. These experimental observations were described by a model based on the assumption (1) that potentiation is linearly related to a residual substance, R(t), which accumulates in the nerve terminal during repetitive stimulation, and (2) that each nerve impulse adds an identical increment, r, of this residual substance. The data were not described by assuming a 4th power relationship between potentiation and R(t). 6. The upward inflexion in potentiation (see paragraph 4) is described by the model as resulting from an increase in the time constant for the decay of potentiation as the magnitude of potentiation increases. 7. The increment of residual substance r added by each impulse was independent of the amount of transmitter released during the conditioning train. This increment typically increased transmitter release by amount 1% of the control level in the absence of potentiation. 8. Suggestions are given to explain why potentiation of transmitter release, which is thought to arise from an accumulation of Ca-2+ in the nerve terminal, can be described assuming a linear relationship between potentiation and R(t), the proposed substance responsible for potentiation, under experimental conditions in which a 3rd to 4th power relationship would be expected to exist between external Ca concentration and evoked transmitter release."} {"id": "PMID:165287", "title": "The electrical basis of excitation and inhibition in the rat anoccygeus muscle.", "content": "1. The transmembrane potential of smooth muscle cells of the rat anococcygeus muscle was studied with micro-electrodes. The muscle had a mean resting membrane potential of --61-5 mV and normally lacked spontaneous mechanical and electrical activity. 2. Stimulation of intramural nerves with single pulses produced a small depolarization and contraction. At frequencies greater than 0.5 Hz a second component occurred which had a maximum value of 35--51 mV with short trains at 30 Hz. Spike potentials were rarely seen. Depolarization was accompanied by a decrease in membrane resistance. 3. Noradrenaline (3 times 10-minus 5 M) and guanethidine (3 times 10-minus 5 M) both depolarized the membrane and produced contraction. Initially, oscillations in the membrane potential were oftern seen. 4. Intramural nerve stimulation in the presence of guanethidine damped the oscillations and produced relaxation. This was accompanied by neither hyperpolarization nor a change in membrane resistance. 5. TEA (1 mM) depolarized the membrane (--47-6 mV) and initiated spontaneous activity. Field stimulation evoked spikes with overshoot.", "contents": "The electrical basis of excitation and inhibition in the rat anoccygeus muscle. 1. The transmembrane potential of smooth muscle cells of the rat anococcygeus muscle was studied with micro-electrodes. The muscle had a mean resting membrane potential of --61-5 mV and normally lacked spontaneous mechanical and electrical activity. 2. Stimulation of intramural nerves with single pulses produced a small depolarization and contraction. At frequencies greater than 0.5 Hz a second component occurred which had a maximum value of 35--51 mV with short trains at 30 Hz. Spike potentials were rarely seen. Depolarization was accompanied by a decrease in membrane resistance. 3. Noradrenaline (3 times 10-minus 5 M) and guanethidine (3 times 10-minus 5 M) both depolarized the membrane and produced contraction. Initially, oscillations in the membrane potential were oftern seen. 4. Intramural nerve stimulation in the presence of guanethidine damped the oscillations and produced relaxation. This was accompanied by neither hyperpolarization nor a change in membrane resistance. 5. TEA (1 mM) depolarized the membrane (--47-6 mV) and initiated spontaneous activity. Field stimulation evoked spikes with overshoot."} {"id": "PMID:165288", "title": "Detachment of structurally intact nerve endings from chromatolytic neurones of rat superior cervical ganglion during the depression of synaptic transmission induced by post-ganglionic axotomy.", "content": "1. Electrophysiological studies showed that injury of post-ganglionic nerve fibres leads to severe and prolonged depression of synaptic transmission through the rat superior cervical ganglion, beginning within 24 h. This is in line with the results of previous studies in other species and upon other neurones. 2. electron microscopy after post-ganglionic axotomy revealed nerve endings of presynaptic type with all the specialized membrane-related features of a synaptic zone, but which were not apposed to any post-synaptic nervous element. These umusual profiles were interpreted as detached presynaptic nerve endings. In normal and control ganglia, such profiles formed at most 0-5% of all vesicle-containing profiles of presynaptic type; in ganglia with all major post-ganglionic branches cut the proportion rose to approximately 7%, between 3 and 7 d post-operatively. Over this period, the mean incidence of chromatolytic neurones was 74-6%. 3. Concomitantly, the incidence of synapses within the ganglion fell by about 75%, reaching its lowest levels between 3 and 7 d post-operatively. There was strikingly little evidence of persistence of post-synaptic membrane specializations ('membrane thickenings') following detachment of synapses. 4. At longer survival intervals the incidence of synapses gradually increased, and that of detached nerve endings gradually decreased; recovery was well advanced by 42 d. 5. The fall in the incidence of synapses was closely paralleled by a fall in the incidence of desmosome-like attachments in the ganglion; the incidence of such attachments was found to be correlated to a significant degree with that of synapses. 6. It is concluded that most or all of the synapses upon sympathetic neurones become physically dissociated during the chromatolytic reaction of these neurones to axotomy. The failure to persist of ultrastructurally specialized post-synaptic sites, and the loss of desmosomes (particularly marked for those involving purely post-ganglionic nervous elements) suggest that the post-ganglionic neurone is losing all its specializations for attachment. 7. Some evidence suggests that the satellite cells may effect the final separation between pre- and post-synaptic structures.", "contents": "Detachment of structurally intact nerve endings from chromatolytic neurones of rat superior cervical ganglion during the depression of synaptic transmission induced by post-ganglionic axotomy. 1. Electrophysiological studies showed that injury of post-ganglionic nerve fibres leads to severe and prolonged depression of synaptic transmission through the rat superior cervical ganglion, beginning within 24 h. This is in line with the results of previous studies in other species and upon other neurones. 2. electron microscopy after post-ganglionic axotomy revealed nerve endings of presynaptic type with all the specialized membrane-related features of a synaptic zone, but which were not apposed to any post-synaptic nervous element. These umusual profiles were interpreted as detached presynaptic nerve endings. In normal and control ganglia, such profiles formed at most 0-5% of all vesicle-containing profiles of presynaptic type; in ganglia with all major post-ganglionic branches cut the proportion rose to approximately 7%, between 3 and 7 d post-operatively. Over this period, the mean incidence of chromatolytic neurones was 74-6%. 3. Concomitantly, the incidence of synapses within the ganglion fell by about 75%, reaching its lowest levels between 3 and 7 d post-operatively. There was strikingly little evidence of persistence of post-synaptic membrane specializations ('membrane thickenings') following detachment of synapses. 4. At longer survival intervals the incidence of synapses gradually increased, and that of detached nerve endings gradually decreased; recovery was well advanced by 42 d. 5. The fall in the incidence of synapses was closely paralleled by a fall in the incidence of desmosome-like attachments in the ganglion; the incidence of such attachments was found to be correlated to a significant degree with that of synapses. 6. It is concluded that most or all of the synapses upon sympathetic neurones become physically dissociated during the chromatolytic reaction of these neurones to axotomy. The failure to persist of ultrastructurally specialized post-synaptic sites, and the loss of desmosomes (particularly marked for those involving purely post-ganglionic nervous elements) suggest that the post-ganglionic neurone is losing all its specializations for attachment. 7. Some evidence suggests that the satellite cells may effect the final separation between pre- and post-synaptic structures."} {"id": "PMID:165291", "title": "Stimulation and inhibition with LH and other hormones of female mammalian meiosis in vitro.", "content": "Utilizing some known physiological preovulatory hormone levels and specific cytological end-points, experiments were carried out with two different media to obtain a clearer understanding of meiotic maturation in vitro of ewe, cow, monkey and human oocytes. In the first series of experiments, it was shown that, in McCoy's medium, ovine LH, prostaglandin E1 and ovine prolactin increased the percentage of divisions of ewe oocytes, without cAMP as a demonstrable intermediate. Monkey oocytes incubated in McCoy's medium with fetal calf serum were stimulated by ovine LH, prostaglandin E2 or cAMP. Human oocytes were stimulated to divide in Diploid medium by ovine LH, oestradiol-17 beta with LH added later, or prostaglandin E1. Diploid medium containing added sheep serum markedly inhibited the meiotic activity of ewe oocytes when ovine LH, HCG, cAMP, prostaglandin E1 and E2 of prolactin were added. This effect was studied by separating the contained fetal calf and sheep sera. It was noted that when LH, HCG, or prostaglandins E1 and E2 were added to a system utilizing fetal calf serum, only spontaneous resumption of meiosis occurred: stimulated and spontaneous activity were reduced when cAMP or prolactin were added. The inhibition of ewe oocyte maturation in Diploid medium with sheep serum and additives was also seen with cow oocytes incubated in Diploid medium containing fetal calf serum and LH, HCG, cAMP or prostaglandin E1 and E2. Cow oocytes incubated in McCoy's medium with equivalent fetal calf serum and added LH were sharply inhibited but spontaneous maturation persisted in the presence of added HCG, cAMP or bovine prolactin.", "contents": "Stimulation and inhibition with LH and other hormones of female mammalian meiosis in vitro. Utilizing some known physiological preovulatory hormone levels and specific cytological end-points, experiments were carried out with two different media to obtain a clearer understanding of meiotic maturation in vitro of ewe, cow, monkey and human oocytes. In the first series of experiments, it was shown that, in McCoy's medium, ovine LH, prostaglandin E1 and ovine prolactin increased the percentage of divisions of ewe oocytes, without cAMP as a demonstrable intermediate. Monkey oocytes incubated in McCoy's medium with fetal calf serum were stimulated by ovine LH, prostaglandin E2 or cAMP. Human oocytes were stimulated to divide in Diploid medium by ovine LH, oestradiol-17 beta with LH added later, or prostaglandin E1. Diploid medium containing added sheep serum markedly inhibited the meiotic activity of ewe oocytes when ovine LH, HCG, cAMP, prostaglandin E1 and E2 of prolactin were added. This effect was studied by separating the contained fetal calf and sheep sera. It was noted that when LH, HCG, or prostaglandins E1 and E2 were added to a system utilizing fetal calf serum, only spontaneous resumption of meiosis occurred: stimulated and spontaneous activity were reduced when cAMP or prolactin were added. The inhibition of ewe oocyte maturation in Diploid medium with sheep serum and additives was also seen with cow oocytes incubated in Diploid medium containing fetal calf serum and LH, HCG, cAMP or prostaglandin E1 and E2. Cow oocytes incubated in McCoy's medium with equivalent fetal calf serum and added LH were sharply inhibited but spontaneous maturation persisted in the presence of added HCG, cAMP or bovine prolactin."} {"id": "PMID:165292", "title": "Distribution of delta-5 -3beta-hydroxysteroid dehydrogenase activity in the Graafian follicle of the sheep.", "content": "The localization of delta-5 -3beta-hydroxysteroid dehydrogenase (3 beta-HSD) has been examined in ovarian follicles in vivo and in vitro, and related to oestrogen and progesterone production. In vivo, during the oestrous cycle, enzyme activity was restricted to the theca interna of the one or two most advanced follicles in each animal, but was present only between Day 2 and 5 and between Day 13 and ovulation. High levels of oestrogen were found in the ovarian venous blood only when follicles containing 3 beta-HSD were present. When sheep were injected with PMSG, the theca interna in a number ofsmall follicles acquired 3 beta-HSD activity and began to secrete oestrogen within 12 hr of the injection. The enzyme was not detected in the membrana granulosa of any follicles before ovulation but within a few hours of ovulation, 3 beta-HSD activity was present in the granulosa lutein cells. In vitro, large activated follicles exhibited 3 beta-HSD activity in the theca interna and secreted high levels of oestrogen into the culture medium. When LH was added to the medium oestrogen secretion was inhibited; within 48 hr, the follicles were secreting high levels of progesterone, and 3 beta-HSD activity was present in both the membrana granulosa and the theca interna. Dibutyryl cyclic adenosine monophosphate mimicked the effect of LH in suppressing oestrogen secretiion, but did not induce production of progesterone; the distribution of 3 beta-HSD activity infollicles treated with this nucleotide was the same as in those cultured in control medium.", "contents": "Distribution of delta-5 -3beta-hydroxysteroid dehydrogenase activity in the Graafian follicle of the sheep. The localization of delta-5 -3beta-hydroxysteroid dehydrogenase (3 beta-HSD) has been examined in ovarian follicles in vivo and in vitro, and related to oestrogen and progesterone production. In vivo, during the oestrous cycle, enzyme activity was restricted to the theca interna of the one or two most advanced follicles in each animal, but was present only between Day 2 and 5 and between Day 13 and ovulation. High levels of oestrogen were found in the ovarian venous blood only when follicles containing 3 beta-HSD were present. When sheep were injected with PMSG, the theca interna in a number ofsmall follicles acquired 3 beta-HSD activity and began to secrete oestrogen within 12 hr of the injection. The enzyme was not detected in the membrana granulosa of any follicles before ovulation but within a few hours of ovulation, 3 beta-HSD activity was present in the granulosa lutein cells. In vitro, large activated follicles exhibited 3 beta-HSD activity in the theca interna and secreted high levels of oestrogen into the culture medium. When LH was added to the medium oestrogen secretion was inhibited; within 48 hr, the follicles were secreting high levels of progesterone, and 3 beta-HSD activity was present in both the membrana granulosa and the theca interna. Dibutyryl cyclic adenosine monophosphate mimicked the effect of LH in suppressing oestrogen secretiion, but did not induce production of progesterone; the distribution of 3 beta-HSD activity infollicles treated with this nucleotide was the same as in those cultured in control medium."} {"id": "PMID:165293", "title": "Induction of blastocyst implantation in mice by cyclic AMP.", "content": "Oestrogen administration to female mice with 'delayed' implantation induces changes in the uterus and blastocysts followed by implantation and normal gestation. The second messenger for oestrogen, adenosine 3' :5'-cyclic monophosphate (cAMP), was instilled into the uterine lumen of females with 'delayed implanting' blastocysts to determinewhether it also is able to induce implantation. Implantation of the blastocysts was induced by cAMP but the pregnancies were not maintained to tem. These results are discussed with respect to the changes in blastocysts induced by cAMP and with respect to the reported contraceptive effects of cAMP in normal mice.", "contents": "Induction of blastocyst implantation in mice by cyclic AMP. Oestrogen administration to female mice with 'delayed' implantation induces changes in the uterus and blastocysts followed by implantation and normal gestation. The second messenger for oestrogen, adenosine 3' :5'-cyclic monophosphate (cAMP), was instilled into the uterine lumen of females with 'delayed implanting' blastocysts to determinewhether it also is able to induce implantation. Implantation of the blastocysts was induced by cAMP but the pregnancies were not maintained to tem. These results are discussed with respect to the changes in blastocysts induced by cAMP and with respect to the reported contraceptive effects of cAMP in normal mice."} {"id": "PMID:165294", "title": "Reproductive capacity of the mentally retarded.", "content": "Ninety-seven mentally retarded females were studied to evaluate parameters of growth and development of secondary sex characteristics and the incidence of ovulation. These patients were selected on the basis of age and etiological classification. Patients were classified as Down's syndrome, brain damaged, or undifferentiated. The following parameters of growth and development were studied: anthropometric, bone age, and sexual maturation. Sexual maturation studies consisted of breast development, pubic hair, axillary hair, menarche, menstrual pattern, and ovulatory patterns. The following observations were made from this study: 1. Physical growth and secondary sexual development were retarded in all parameters. 2. The undifferentiated and brain damaged groups showed almost identical patterns of growth and development of secondary sexual characteristics. 3. The Down's syndrome group was the most retarded in physical growth and in secondary sexual development. 4. Skeletal age was a better guide than chronological age or height and body weight to the prediction of development of secondary sex characteristics and age at onset of menarche. 5. In 26 mentally retarded females who had achieved menarche the incidence of ovulation was approximately 60 percent.", "contents": "Reproductive capacity of the mentally retarded. Ninety-seven mentally retarded females were studied to evaluate parameters of growth and development of secondary sex characteristics and the incidence of ovulation. These patients were selected on the basis of age and etiological classification. Patients were classified as Down's syndrome, brain damaged, or undifferentiated. The following parameters of growth and development were studied: anthropometric, bone age, and sexual maturation. Sexual maturation studies consisted of breast development, pubic hair, axillary hair, menarche, menstrual pattern, and ovulatory patterns. The following observations were made from this study: 1. Physical growth and secondary sexual development were retarded in all parameters. 2. The undifferentiated and brain damaged groups showed almost identical patterns of growth and development of secondary sexual characteristics. 3. The Down's syndrome group was the most retarded in physical growth and in secondary sexual development. 4. Skeletal age was a better guide than chronological age or height and body weight to the prediction of development of secondary sex characteristics and age at onset of menarche. 5. In 26 mentally retarded females who had achieved menarche the incidence of ovulation was approximately 60 percent."} {"id": "PMID:165297", "title": "Cell-envelope proteins of Bordetella pertussis.", "content": "Cell-envelope polypeptides of eight phase-I and five phase-IV strains of Bordetella pertussis were compared by SDS-polyacrylamide gel electrophoresis. All phase-I strains gave a strikingly similar but complex pattern of protein bands, which did not appear to vary with known differences in heat-labile agglutinogens. Phase-IV strains gave the same pattern as phase-I strains, except that one band was missing and another was either much reduced or absent. Envelopes from phase-I strains grown in Hornibrook medium rich in Mg-2+ ions to produce \"antigenically-modulated\" C-mode cells gave a pattern of bands indistinguishable from phase-IV strains. A phase-IV strain grown in the high-Mg-2+ medium gave the same pattern of bands as when grown in unmodified Hornibrook medium. We suggest that the two polypeptide bands that show changes may be responsible for one or more of the immunological or physiopathological activities that are lost during phase variation and antigenic modulation in B. pertussis.", "contents": "Cell-envelope proteins of Bordetella pertussis. Cell-envelope polypeptides of eight phase-I and five phase-IV strains of Bordetella pertussis were compared by SDS-polyacrylamide gel electrophoresis. All phase-I strains gave a strikingly similar but complex pattern of protein bands, which did not appear to vary with known differences in heat-labile agglutinogens. Phase-IV strains gave the same pattern as phase-I strains, except that one band was missing and another was either much reduced or absent. Envelopes from phase-I strains grown in Hornibrook medium rich in Mg-2+ ions to produce \"antigenically-modulated\" C-mode cells gave a pattern of bands indistinguishable from phase-IV strains. A phase-IV strain grown in the high-Mg-2+ medium gave the same pattern of bands as when grown in unmodified Hornibrook medium. We suggest that the two polypeptide bands that show changes may be responsible for one or more of the immunological or physiopathological activities that are lost during phase variation and antigenic modulation in B. pertussis."} {"id": "PMID:165299", "title": "Testing for possible effects of cedar wood shavings and diet on occurrence of mammary gland tumors and hepatomas in C3H-A-vy and C3H-Avy-fB mice.", "content": "C3H-A-vy and C3H-A-VY-FB mice transferred from our colony to the laboratory of Dr. J. R. Sabine in Australia had a markedly reduced incidence of both hepatomas and mammary tumors. Sabine and co-workers (J Natl Cancer Inst 50: 1237-1242, 1973) attributed the low incidence of tumors in their laboratory compared to the high incidence in this laboratory to the fact that we routinely use red cedar shavings in the bedding, whereas they use sawdust, predominantly Doublas fir. Results of tests in this laboratory showed that the difference in occurrence of tumors could not be attributed directly to either a difference in diet or bedding. There was no evidence that the cedar shavings were carcinogenic. The animals in Australia on bedding without cedar shavings were not as healthy as our animals, in that they did not grow as well and were infested with ectoparasites; apparently these factors caused the reduced occurrence of tumors.", "contents": "Testing for possible effects of cedar wood shavings and diet on occurrence of mammary gland tumors and hepatomas in C3H-A-vy and C3H-Avy-fB mice. C3H-A-vy and C3H-A-VY-FB mice transferred from our colony to the laboratory of Dr. J. R. Sabine in Australia had a markedly reduced incidence of both hepatomas and mammary tumors. Sabine and co-workers (J Natl Cancer Inst 50: 1237-1242, 1973) attributed the low incidence of tumors in their laboratory compared to the high incidence in this laboratory to the fact that we routinely use red cedar shavings in the bedding, whereas they use sawdust, predominantly Doublas fir. Results of tests in this laboratory showed that the difference in occurrence of tumors could not be attributed directly to either a difference in diet or bedding. There was no evidence that the cedar shavings were carcinogenic. The animals in Australia on bedding without cedar shavings were not as healthy as our animals, in that they did not grow as well and were infested with ectoparasites; apparently these factors caused the reduced occurrence of tumors."} {"id": "PMID:165300", "title": "Carcinogenicity of 5-nitrofurans and related compounds with amino-heterocyclic substituents.", "content": "Carcinogenicity of eight 5-nitrofurans with heterocyclic substituents at the 2-position of the furan ring was investigated by feeding the chemicals to Sprague-Dawley female rats. N-[5-(5-nitro-2-furyl)-1,3,4-thiadiazol-2-yl]acetamide induced in 30 rats the highest incidence of tumors with the greatest number of tissues involved: forestomach squamous cell tumors (22), kidney pelvis transitional cell carcinomas (15), pulmonary alveolar cell carcinomas (16), hemangioendothelialsarcomas (20) of the intestine, mesentery, liver, lung, and pancreas, and a few tumors of other tissues. 2-Amino-5-(5-nitro-2-furyl)-1,3,4-thiadiazole, 2-amino-5-(5-nitro-2furyl)-1,3,4-oxadiazole, and trans-2-[dimethylamino)methylimino]-5-[2-(5-nitro-2-furyl)vinyl]-1,3,4-oxadiazole produced high incidences of mammary tumors. The other four 5-nitrofurans tested: N-[4-(5-NITRO-2-FURYL)-2-THIAZOLYL]ACETAMIDE;2,3,4-TRIFLUORO-N-[4-(5-NITRO-2-furyl)-2-thiazoly]acetamide;5-(5-nitro-2-furyl)-1,3,4-oxadiazol-2-ol; and N-( [3-(5-nitro-2-furyl)-1,2,4-oxadiazol-5-yl]methyl)acetamide were associated with tumor incidences of 40-60%. Two other chemicals were also tested: 2-Amino-5-nitrothiazole caused a low incidence of breast and kidney pelvis tumors, and 2-amino-4-(p-nitrophenyl)thiazole induced a high incidence of breast and salivary gland adenocarcinomas and lymphomas.", "contents": "Carcinogenicity of 5-nitrofurans and related compounds with amino-heterocyclic substituents. Carcinogenicity of eight 5-nitrofurans with heterocyclic substituents at the 2-position of the furan ring was investigated by feeding the chemicals to Sprague-Dawley female rats. N-[5-(5-nitro-2-furyl)-1,3,4-thiadiazol-2-yl]acetamide induced in 30 rats the highest incidence of tumors with the greatest number of tissues involved: forestomach squamous cell tumors (22), kidney pelvis transitional cell carcinomas (15), pulmonary alveolar cell carcinomas (16), hemangioendothelialsarcomas (20) of the intestine, mesentery, liver, lung, and pancreas, and a few tumors of other tissues. 2-Amino-5-(5-nitro-2-furyl)-1,3,4-thiadiazole, 2-amino-5-(5-nitro-2furyl)-1,3,4-oxadiazole, and trans-2-[dimethylamino)methylimino]-5-[2-(5-nitro-2-furyl)vinyl]-1,3,4-oxadiazole produced high incidences of mammary tumors. The other four 5-nitrofurans tested: N-[4-(5-NITRO-2-FURYL)-2-THIAZOLYL]ACETAMIDE;2,3,4-TRIFLUORO-N-[4-(5-NITRO-2-furyl)-2-thiazoly]acetamide;5-(5-nitro-2-furyl)-1,3,4-oxadiazol-2-ol; and N-( [3-(5-nitro-2-furyl)-1,2,4-oxadiazol-5-yl]methyl)acetamide were associated with tumor incidences of 40-60%. Two other chemicals were also tested: 2-Amino-5-nitrothiazole caused a low incidence of breast and kidney pelvis tumors, and 2-amino-4-(p-nitrophenyl)thiazole induced a high incidence of breast and salivary gland adenocarcinomas and lymphomas."} {"id": "PMID:165301", "title": "Characterization of spontaneous, chemicak, and viral transformants of a C3H/3T3-type mouse cell line by transplantation into young chick blastoderms.", "content": "Cells from a C3H/3T3-type cell line were transplanted into defects of the lower layer of stage-4 chick blastoderms before and after \"spontaneous,\" chemical, and viral transformation. To check the validity of inhibition of lower-layer defect closure as a criterion of malignancy, we compared the behavior of the lower layer toward these cells with their in vitro growth pattern, their capacity to invade embryonic chick skin explants that were organotypicaly cultured, and their tumorigenicity in syngeneic mice. No false-positive results were observed with either test. The study of the in vitro growth pattern gave false-negative results during the early phase of spontaneous transformation, whereas these cells, exhibiting an untransformed growth pattern, were shown to be malignant by the other tests. We concluded that the inhibition of lower-layer defect closure is a reliable, sensitive and rapid test for the detection of malignancy in tissue-cultured cells from any source.", "contents": "Characterization of spontaneous, chemicak, and viral transformants of a C3H/3T3-type mouse cell line by transplantation into young chick blastoderms. Cells from a C3H/3T3-type cell line were transplanted into defects of the lower layer of stage-4 chick blastoderms before and after \"spontaneous,\" chemical, and viral transformation. To check the validity of inhibition of lower-layer defect closure as a criterion of malignancy, we compared the behavior of the lower layer toward these cells with their in vitro growth pattern, their capacity to invade embryonic chick skin explants that were organotypicaly cultured, and their tumorigenicity in syngeneic mice. No false-positive results were observed with either test. The study of the in vitro growth pattern gave false-negative results during the early phase of spontaneous transformation, whereas these cells, exhibiting an untransformed growth pattern, were shown to be malignant by the other tests. We concluded that the inhibition of lower-layer defect closure is a reliable, sensitive and rapid test for the detection of malignancy in tissue-cultured cells from any source."} {"id": "PMID:165302", "title": "Sarcoma in a hamster inoculated with BK virus, a human papovavirus.", "content": "An undifferentiated sarcoma occurred in 1 of 52 hamsters inoculated when newborn with BK virus (BKV), A SIMIAN VIRUS 40 (SV40)-related human papovavirus. It was transplantable and grew in tissue culture. Sera of tumor-bearing hamsters were without antibodies reactive to BKV virion antigens in hemagglutination-inhibition and neutralizationtexts, but contained antibodies reactive in immunofluorescence (IF) tests to SV40 T antigen in SV40-TRANSFORMED CELLS AND TO ANTIGENS IN CELLS ACUTELY INFECTED WITH BKV or SV40. The IF reaction between tumor cells and sera of tumor-bearing hamsters was minimal in texts of tumor cells of an early passage but satisfactory in tests of cells from a later passage. Fusion of tumor cells with permissive (monkey and human) cells, induced by inactivated Sendai virus, did not lead to recovery of infectious BKV. Immunization of hamster with BKV or SV40 failed to protect against challenge with tumor cells. There was considerable cross-reactivity between the T antigens of BKV and SV40 viruses", "contents": "Sarcoma in a hamster inoculated with BK virus, a human papovavirus. An undifferentiated sarcoma occurred in 1 of 52 hamsters inoculated when newborn with BK virus (BKV), A SIMIAN VIRUS 40 (SV40)-related human papovavirus. It was transplantable and grew in tissue culture. Sera of tumor-bearing hamsters were without antibodies reactive to BKV virion antigens in hemagglutination-inhibition and neutralizationtexts, but contained antibodies reactive in immunofluorescence (IF) tests to SV40 T antigen in SV40-TRANSFORMED CELLS AND TO ANTIGENS IN CELLS ACUTELY INFECTED WITH BKV or SV40. The IF reaction between tumor cells and sera of tumor-bearing hamsters was minimal in texts of tumor cells of an early passage but satisfactory in tests of cells from a later passage. Fusion of tumor cells with permissive (monkey and human) cells, induced by inactivated Sendai virus, did not lead to recovery of infectious BKV. Immunization of hamster with BKV or SV40 failed to protect against challenge with tumor cells. There was considerable cross-reactivity between the T antigens of BKV and SV40 viruses"} {"id": "PMID:165303", "title": "Antibody to herpes simplex virus type 2-induced nonstructural proteins in women with cervical cancer and in control groups.", "content": "Sera obtained from 15 patients with cervical cancer, 10 patients with breast cancer, and 15 control women, individually matched with the cervical cancer patients, were examined for antibodies to early proteins synthesized in herpes simplex virus type 2 (HSV-2)-infected cells. The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. The relative reactivity to a major early nonstructural protein (VP134) was used to compare these selected sera. The results obtained suggest that cervical cancer patients possess sera with a higher reactivity to VP134 than breast cancer patients or matched healthy women,and that serum reactivity is independent of the level of neutralizing antibodies to HSV-2.", "contents": "Antibody to herpes simplex virus type 2-induced nonstructural proteins in women with cervical cancer and in control groups. Sera obtained from 15 patients with cervical cancer, 10 patients with breast cancer, and 15 control women, individually matched with the cervical cancer patients, were examined for antibodies to early proteins synthesized in herpes simplex virus type 2 (HSV-2)-infected cells. The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. The relative reactivity to a major early nonstructural protein (VP134) was used to compare these selected sera. The results obtained suggest that cervical cancer patients possess sera with a higher reactivity to VP134 than breast cancer patients or matched healthy women,and that serum reactivity is independent of the level of neutralizing antibodies to HSV-2."} {"id": "PMID:165304", "title": "Inhibition of embryonic cell aggregation by neoplastic cells.", "content": "The effects of normal and malignant cells on the aggregation of embryonic cells in gyratory shaker cultures were compared. The addition of 1 times 10-5 simian virus 40 (SV40)-transformed BALB/3T3 (SV40-3T3) cells to 6 times 10-6 embryonic neural retina cells caused a highly significant greater reduct on (22.7 percent) in aggregate diameter than the addition of untransformed BALB/3T3 (3T3) cells. The ratio of the number of single cells to the number of aggregates was significantly higher for cultures containing SV40-3T3 cells than for the cultures containing 3T3 cells. This effect was concentration dependent in the presence of cultured Ehrlich-Lettre hyperdiploid (ELD) ascites cells; however, media from ELD cell cultures or ELD cell sonicates resulted in aggregates of greater diameter and lower ratios of single cells to aggregates. This approach may provide a sensitive assay system for the interactions of tumor and other cells in vitro.", "contents": "Inhibition of embryonic cell aggregation by neoplastic cells. The effects of normal and malignant cells on the aggregation of embryonic cells in gyratory shaker cultures were compared. The addition of 1 times 10-5 simian virus 40 (SV40)-transformed BALB/3T3 (SV40-3T3) cells to 6 times 10-6 embryonic neural retina cells caused a highly significant greater reduct on (22.7 percent) in aggregate diameter than the addition of untransformed BALB/3T3 (3T3) cells. The ratio of the number of single cells to the number of aggregates was significantly higher for cultures containing SV40-3T3 cells than for the cultures containing 3T3 cells. This effect was concentration dependent in the presence of cultured Ehrlich-Lettre hyperdiploid (ELD) ascites cells; however, media from ELD cell cultures or ELD cell sonicates resulted in aggregates of greater diameter and lower ratios of single cells to aggregates. This approach may provide a sensitive assay system for the interactions of tumor and other cells in vitro."} {"id": "PMID:165305", "title": "Microvesicles and vesicles of multivesicular bodies versus \"virus-like\" particles.", "content": "Pellets obtained by the centrifugation of unfiltered or filtered fetal bovine serum (FBS) contained, among other things, numerous elongate and spherical microvesicles, ranging from 30 to 60 nm. They possessed a trilaminar (unit membrane) envelope and a moderately electron-dense core. Vesicles of multivesicular bodies and microvesicles associated with secretory epithelial cells and human lymphoblastoid cells in suspension culture possessed the same structure and were in the same size range as the serum microvesicles. These structures were either normal cell components or they represented the breakdown products of normal cell components and should not be confused with viruses. Though microvesicles of FBS may have been involved in the tissue culture material, at least some of the microvesicles associated with, and phagocytosed by, human lymphoblastoid cells in suspension and those in the lumen of acini of the baboon prostate were derived from the breakdown of the cristae of mitochondria in degenerating cells.", "contents": "Microvesicles and vesicles of multivesicular bodies versus \"virus-like\" particles. Pellets obtained by the centrifugation of unfiltered or filtered fetal bovine serum (FBS) contained, among other things, numerous elongate and spherical microvesicles, ranging from 30 to 60 nm. They possessed a trilaminar (unit membrane) envelope and a moderately electron-dense core. Vesicles of multivesicular bodies and microvesicles associated with secretory epithelial cells and human lymphoblastoid cells in suspension culture possessed the same structure and were in the same size range as the serum microvesicles. These structures were either normal cell components or they represented the breakdown products of normal cell components and should not be confused with viruses. Though microvesicles of FBS may have been involved in the tissue culture material, at least some of the microvesicles associated with, and phagocytosed by, human lymphoblastoid cells in suspension and those in the lumen of acini of the baboon prostate were derived from the breakdown of the cristae of mitochondria in degenerating cells."} {"id": "PMID:165306", "title": "Mammary tumor virus particles in the submaxillary gland, seminal vesicle, and nonmammary tumors of wild mice.", "content": "Type-B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands of 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type-B particles were also detected in 3 9f 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic type-A virus particles were found in 7 spontaneous nonmammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type-C virus particles were also detected in many of these tissues.", "contents": "Mammary tumor virus particles in the submaxillary gland, seminal vesicle, and nonmammary tumors of wild mice. Type-B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands of 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type-B particles were also detected in 3 9f 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic type-A virus particles were found in 7 spontaneous nonmammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type-C virus particles were also detected in many of these tissues."} {"id": "PMID:165307", "title": "Immunization with a lipid-conjugated membrane antigen to suppress growth of a fibrosarcoma induced by simian virus 40.", "content": "The covalent conjugation of fatty acid to a tumor cell membrane preparation transformed it from an antigen that enhanced tumor growth to one that suppressed it. A crude cell membrane preparation was made by sequential hypertonic and hypotonic salt extraction of tumor cells from a fibrosarcoma induced in hamsters by simian virus 40. The membranes were chemically conjugated with dodecanoic anhydride in 0.5 M carbonate buffer (pH 9.0). Injection of unmodified membranes 10 days before transplantation of live tumor cells produced clear-cut enhancement of the tumor growth rate. In contrast, injection of lipid-conjugated membranes in a similar dose and protocol suppressed tumor growth. The lymphoid proliferative reactions to the tumor cells as demonstrated by the histology of both the tumor and regional lymph nodes were consistent with the hypothesis that unmodified membranes stimulated the production of antibody which participated in the enhancement of tumor growth, and that lipid-conjugated membranes stimulated the production of cell-mediated immunity which suppressed this growth.", "contents": "Immunization with a lipid-conjugated membrane antigen to suppress growth of a fibrosarcoma induced by simian virus 40. The covalent conjugation of fatty acid to a tumor cell membrane preparation transformed it from an antigen that enhanced tumor growth to one that suppressed it. A crude cell membrane preparation was made by sequential hypertonic and hypotonic salt extraction of tumor cells from a fibrosarcoma induced in hamsters by simian virus 40. The membranes were chemically conjugated with dodecanoic anhydride in 0.5 M carbonate buffer (pH 9.0). Injection of unmodified membranes 10 days before transplantation of live tumor cells produced clear-cut enhancement of the tumor growth rate. In contrast, injection of lipid-conjugated membranes in a similar dose and protocol suppressed tumor growth. The lymphoid proliferative reactions to the tumor cells as demonstrated by the histology of both the tumor and regional lymph nodes were consistent with the hypothesis that unmodified membranes stimulated the production of antibody which participated in the enhancement of tumor growth, and that lipid-conjugated membranes stimulated the production of cell-mediated immunity which suppressed this growth."} {"id": "PMID:165308", "title": "Inhalation studies of nickel sulfide in pulmonary carcinogenesis of rats.", "content": "Two hundred twenty-six specific pathogenfree male and female F344 rats were exposed to nickel sulfide inhalations for 78 weeks (5 days/wk, 6 hr/day) and observed for an adiditional 30-week period. For the same amount of time, 214 rats were exposed to filtered room air and served as controls. Rats exposed to nickel sulfide showed a significantly higher incidence of pulmonary hyperplastic and neoplastic lesions originating from the bronchial and bronchiloo-alveloar segments. The overall incidence of lung tumors in the animals treated with nickel sulfide was 14 percent compared with 1 percent in the controls. Pulmonary inflammatory reactions were also greatly increased. Injection of an agent (hexachlorotetra-fluorobutane) that induced lung infarction did not increase the proportion of animals having lesions, nor did it alter the type of lesions found in animals exposed to nickel sulfide.", "contents": "Inhalation studies of nickel sulfide in pulmonary carcinogenesis of rats. Two hundred twenty-six specific pathogenfree male and female F344 rats were exposed to nickel sulfide inhalations for 78 weeks (5 days/wk, 6 hr/day) and observed for an adiditional 30-week period. For the same amount of time, 214 rats were exposed to filtered room air and served as controls. Rats exposed to nickel sulfide showed a significantly higher incidence of pulmonary hyperplastic and neoplastic lesions originating from the bronchial and bronchiloo-alveloar segments. The overall incidence of lung tumors in the animals treated with nickel sulfide was 14 percent compared with 1 percent in the controls. Pulmonary inflammatory reactions were also greatly increased. Injection of an agent (hexachlorotetra-fluorobutane) that induced lung infarction did not increase the proportion of animals having lesions, nor did it alter the type of lesions found in animals exposed to nickel sulfide."} {"id": "PMID:165309", "title": "Vertical transmission of C-type viruses: their presence in baboon follicular oocytes and tubal ova.", "content": "C-type viruses were found in baboon follicular oocytes and tubal ova adjacent to the plasma membrane in the perivitelline space or along the inner margin of the zona pellucida. Their presence support the concept of vertical transmission of C-type viruses.", "contents": "Vertical transmission of C-type viruses: their presence in baboon follicular oocytes and tubal ova. C-type viruses were found in baboon follicular oocytes and tubal ova adjacent to the plasma membrane in the perivitelline space or along the inner margin of the zona pellucida. Their presence support the concept of vertical transmission of C-type viruses."} {"id": "PMID:165310", "title": "Modification of diethylnitrosamine liver carcinogenesis with phenobarbital but not with immunosuppression.", "content": "Administration of 40 ppm diethylnitrosamine (DENA) in the drinking water for 10 weeks to male Fischer rats led to hepatocellular carcinoma in 100 percent with metastasis to the lung in 40 percent, of the animals living for the full experimental period of 20 weeks. Concurrent feeding of phenobarbital and DENA for 10 weeks produced cancer of the liver in 77 percent of the animals, but only 9 percent had metastases in the lung. A brief regimen of DENA for 4 weeks, followed by 16 weeks of observation, induced cancer of the liver in only 13 percent of the rats. Administration of phenobarbital, begun 1 week after cessation of DENA intake and terminated at week 20, led to liver cancer in 64 percent of the rodents. Hydroxyurea had no effect on this enhancement. Treatment with a purified gamma fraction of antilymphocytic serum after the DENA did not influence the outcome. Thus phenobarbital given together with DENA reduced the severity of the carcinogenic process, but when it was given after the hepatocarcinogen, it increased the effect.", "contents": "Modification of diethylnitrosamine liver carcinogenesis with phenobarbital but not with immunosuppression. Administration of 40 ppm diethylnitrosamine (DENA) in the drinking water for 10 weeks to male Fischer rats led to hepatocellular carcinoma in 100 percent with metastasis to the lung in 40 percent, of the animals living for the full experimental period of 20 weeks. Concurrent feeding of phenobarbital and DENA for 10 weeks produced cancer of the liver in 77 percent of the animals, but only 9 percent had metastases in the lung. A brief regimen of DENA for 4 weeks, followed by 16 weeks of observation, induced cancer of the liver in only 13 percent of the rats. Administration of phenobarbital, begun 1 week after cessation of DENA intake and terminated at week 20, led to liver cancer in 64 percent of the rodents. Hydroxyurea had no effect on this enhancement. Treatment with a purified gamma fraction of antilymphocytic serum after the DENA did not influence the outcome. Thus phenobarbital given together with DENA reduced the severity of the carcinogenic process, but when it was given after the hepatocarcinogen, it increased the effect."} {"id": "PMID:165311", "title": "Inhibition of bovine leukemia virus release.", "content": "Sera from 3 cows with the adult form of lymphosarcoma inhibited release of leukemia virus from a cell line of fetal lamb spleen infected with bovine leukemia virus (BLV). Sera from 5 to 7 cattle experimentally infected with BLV also suppressed virus release. The inhibition of virus release was reversible. Sera from cattle with the calf form and the thymic form of lymphosarcoma and normal bovine control sera did not repress virus release.", "contents": "Inhibition of bovine leukemia virus release. Sera from 3 cows with the adult form of lymphosarcoma inhibited release of leukemia virus from a cell line of fetal lamb spleen infected with bovine leukemia virus (BLV). Sera from 5 to 7 cattle experimentally infected with BLV also suppressed virus release. The inhibition of virus release was reversible. Sera from cattle with the calf form and the thymic form of lymphosarcoma and normal bovine control sera did not repress virus release."} {"id": "PMID:165312", "title": "Studies on a transplantable murine rhabdomyosarcoma.", "content": "Well-differentiated rhabdomyosarcomas developed in 8 of 10 BALB/c mice inoculated with cell-free extracts of two lesions arising in bats previously inoculated with the Moloney strain of murine sarcoma virus. The tumors could be transplanted in BALB/c mice and other strains of mice compatible at the H-2 locus. A tumorigenic clonal cell culture line (R2) was established from a transplanted tumor. Ultrastructural studies of the primary and transplanted tumors and R2 cells revealed thick and thin myofilaments characteristic of myoblasts. These cells contained numerous cisternal type-A virus-like particles, but no type-C particles were found. Attempts to recover, rescue, or chemically induce transforming or nontransforming viruses from transplantable tumors and the R2 cell line were unsuccessful. The tumor cells lacked the murine type-C virus gs antigen. Hybridization data confirmed the apparent lack of viral RNA in the tumor cells.", "contents": "Studies on a transplantable murine rhabdomyosarcoma. Well-differentiated rhabdomyosarcomas developed in 8 of 10 BALB/c mice inoculated with cell-free extracts of two lesions arising in bats previously inoculated with the Moloney strain of murine sarcoma virus. The tumors could be transplanted in BALB/c mice and other strains of mice compatible at the H-2 locus. A tumorigenic clonal cell culture line (R2) was established from a transplanted tumor. Ultrastructural studies of the primary and transplanted tumors and R2 cells revealed thick and thin myofilaments characteristic of myoblasts. These cells contained numerous cisternal type-A virus-like particles, but no type-C particles were found. Attempts to recover, rescue, or chemically induce transforming or nontransforming viruses from transplantable tumors and the R2 cell line were unsuccessful. The tumor cells lacked the murine type-C virus gs antigen. Hybridization data confirmed the apparent lack of viral RNA in the tumor cells."} {"id": "PMID:165313", "title": "Long-term primary culture of mouse mammary tumor cells: production of virus.", "content": "Long-term primary cultures of mouse mammary tumor cells proved an excellent source of mouse mammary tumor virus (MMTV). Virus purified from these primary cultures had the same morphologic biochemical, immunologic, and biologic characteristics as MMTV. Quantitation of MMTV-protein equivalents released into the medium was measured by the radioimmunoassay for MMTV. Peak production levels were 20-40 mug MMTV protien equivalents/75-cm-2 flask/24 hours. These cultures produced MMTV for as long as 90 days. MMTV cultivation depended on the initial cell-plating density and hormones. Maximal MMTV release was obtained at a plating density of 1 times 10-6 cells/cm-2 in the presence of insulin and hydrocortisone. Insulin alone gave basal levels of MMTV, and hydrocortisone alone increased MMTV release only three-fold, but insulin and hydrocortisone together effected an eightfold increase in MMTV release. This suggested that hydrocortisone had a primary effect on MMTV release and insulin acted synergistically with hydrocortisone to maximize MMTV release.", "contents": "Long-term primary culture of mouse mammary tumor cells: production of virus. Long-term primary cultures of mouse mammary tumor cells proved an excellent source of mouse mammary tumor virus (MMTV). Virus purified from these primary cultures had the same morphologic biochemical, immunologic, and biologic characteristics as MMTV. Quantitation of MMTV-protein equivalents released into the medium was measured by the radioimmunoassay for MMTV. Peak production levels were 20-40 mug MMTV protien equivalents/75-cm-2 flask/24 hours. These cultures produced MMTV for as long as 90 days. MMTV cultivation depended on the initial cell-plating density and hormones. Maximal MMTV release was obtained at a plating density of 1 times 10-6 cells/cm-2 in the presence of insulin and hydrocortisone. Insulin alone gave basal levels of MMTV, and hydrocortisone alone increased MMTV release only three-fold, but insulin and hydrocortisone together effected an eightfold increase in MMTV release. This suggested that hydrocortisone had a primary effect on MMTV release and insulin acted synergistically with hydrocortisone to maximize MMTV release."} {"id": "PMID:165314", "title": "Immunologic aspects of 1, 2-dimethylhydrazine-induced colon tumors in rats.", "content": "Investigation of immunologic aspects of colon tumors induced in rats by 1,2-dimethylhydrazine demonstrated that: 1) An antigen in an extract of colon tumors was not detected in the normal colon. It was related to antigens in rat fetuses and did not cross-react immunologically with carcinoembryonic antigen. 2) Mucinous adenocarcinomas of the colon were significantly associated spatially with lymphoid follicles.", "contents": "Immunologic aspects of 1, 2-dimethylhydrazine-induced colon tumors in rats. Investigation of immunologic aspects of colon tumors induced in rats by 1,2-dimethylhydrazine demonstrated that: 1) An antigen in an extract of colon tumors was not detected in the normal colon. It was related to antigens in rat fetuses and did not cross-react immunologically with carcinoembryonic antigen. 2) Mucinous adenocarcinomas of the colon were significantly associated spatially with lymphoid follicles."} {"id": "PMID:165315", "title": "Oncogenic transformation of murine lymphoid cells by in vitro infection with Abelson leukemia virus.", "content": "Spleen cell cultures stimulated to DNA synthesis by antigen or mitogen were infected with Abelson virus, a C-type RNA virus inducing nonthymic lymphomas in mice. After 3 days the cells were transferred to mice and caused 100 percent incidence of lymphomas in as few as 29 days. That a number of the tumors were of donor origin, as shown by female karyotypes in recipient male mice, indicated that cells infected by virus in vitro were transformed. The process depended upon both virus and stimulation of lymphocytes in culture. Lymphoid tumors did not develop in mice receiving cells from virus-infected cultures not exposed to antigen or mitogen.", "contents": "Oncogenic transformation of murine lymphoid cells by in vitro infection with Abelson leukemia virus. Spleen cell cultures stimulated to DNA synthesis by antigen or mitogen were infected with Abelson virus, a C-type RNA virus inducing nonthymic lymphomas in mice. After 3 days the cells were transferred to mice and caused 100 percent incidence of lymphomas in as few as 29 days. That a number of the tumors were of donor origin, as shown by female karyotypes in recipient male mice, indicated that cells infected by virus in vitro were transformed. The process depended upon both virus and stimulation of lymphocytes in culture. Lymphoid tumors did not develop in mice receiving cells from virus-infected cultures not exposed to antigen or mitogen."} {"id": "PMID:165316", "title": "Effect of protease inhibitors on focus formation by murine sarcoma virus.", "content": "The effect of six protease inhibitors, isolated from various species of actinomycetes, on focus formation by murine sarcoma virus was examined. Pepstatin was the only inhibitor. The treatment of cells with pepstatin at various times possibly retards the early stage of infection with murine sarcoma virus.", "contents": "Effect of protease inhibitors on focus formation by murine sarcoma virus. The effect of six protease inhibitors, isolated from various species of actinomycetes, on focus formation by murine sarcoma virus was examined. Pepstatin was the only inhibitor. The treatment of cells with pepstatin at various times possibly retards the early stage of infection with murine sarcoma virus."} {"id": "PMID:165323", "title": "Detection of oncornavirus antigenic activity in human urothelial tissues.", "content": "Our studies indicate that certain urologic tissues demonstrate evidence of proteins which compete with the interspecies antigens of C-type ribonucleic acid viruses for binding sites of the feline and murine oncornavirus antiglobulins. This fact indicates either the association of viral antigens within these tissues or the presence of a protein so similar to the interspecies antigen that it cross reacts. Studies are now underway to localize reacting antigens within these urologic cells, to correlate the immunologic properties with enzymatic properties known to be specific for oncornaviruses and to assay the activity of patient sera with isolated interspecies antigens. Sera from patients with urologic malignancies will be tested to determine whether the sera can effectively absorb reactivity from tissue extracts or compete with reagent rabbit antisera raised against the interspecies component of the viruses. Should either activity be detected in patient sera, clinical screening will be undertaken to determine if this approach is applicable to early detection of urologic malignancies.", "contents": "Detection of oncornavirus antigenic activity in human urothelial tissues. Our studies indicate that certain urologic tissues demonstrate evidence of proteins which compete with the interspecies antigens of C-type ribonucleic acid viruses for binding sites of the feline and murine oncornavirus antiglobulins. This fact indicates either the association of viral antigens within these tissues or the presence of a protein so similar to the interspecies antigen that it cross reacts. Studies are now underway to localize reacting antigens within these urologic cells, to correlate the immunologic properties with enzymatic properties known to be specific for oncornaviruses and to assay the activity of patient sera with isolated interspecies antigens. Sera from patients with urologic malignancies will be tested to determine whether the sera can effectively absorb reactivity from tissue extracts or compete with reagent rabbit antisera raised against the interspecies component of the viruses. Should either activity be detected in patient sera, clinical screening will be undertaken to determine if this approach is applicable to early detection of urologic malignancies."} {"id": "PMID:165324", "title": "Androblastoma and germ cell tumor of the same testis: a case report.", "content": "The rare case of a testicular androblastoma associated with a complex germ cell tumor of the same testis is reported. Gynecomastia preceded the clinical appearace of testicular swelling by 3 months, suggesting that the 2 tumors developed contemporaneously and that, in theory, the Sertoli cell tumor is probably dependent on the germ cell tumor.", "contents": "Androblastoma and germ cell tumor of the same testis: a case report. The rare case of a testicular androblastoma associated with a complex germ cell tumor of the same testis is reported. Gynecomastia preceded the clinical appearace of testicular swelling by 3 months, suggesting that the 2 tumors developed contemporaneously and that, in theory, the Sertoli cell tumor is probably dependent on the germ cell tumor."} {"id": "PMID:165326", "title": "[Comparative studies of the therapeutic effect of colistin methanesulfonate administered intramuscularly and intravenously on the acute bacterial infection in mice (author's transl)].", "content": "The therapeutic potencies of colistin methanesulfonate (CLM) was assessed quantitatively in acute infection of mice with clinically isolated strains of Escherichia coli and Pseudomonas aeruginosa, and effect of different routes of administration was compared. There was no detectable difference in the therapeutic effect of CLM when intramuscular (im) or intravenous (iv) administration was initiated one hour after the infection. On the other hand, a significant difference in ED50 given by im and iv administrations was observed, indicating the superiority of iv administration, when the treatment started 4 to approximately hours after the infection. No difference in the therapeutic effect of polymyxin B (PMB) and tetracycline (TC) administered via either im or iv route was found even in the delayed administration. In contrast to PMB and TC, lower toxicity of CLM was determined when it was administered iv rather than im.", "contents": "[Comparative studies of the therapeutic effect of colistin methanesulfonate administered intramuscularly and intravenously on the acute bacterial infection in mice (author's transl)]. The therapeutic potencies of colistin methanesulfonate (CLM) was assessed quantitatively in acute infection of mice with clinically isolated strains of Escherichia coli and Pseudomonas aeruginosa, and effect of different routes of administration was compared. There was no detectable difference in the therapeutic effect of CLM when intramuscular (im) or intravenous (iv) administration was initiated one hour after the infection. On the other hand, a significant difference in ED50 given by im and iv administrations was observed, indicating the superiority of iv administration, when the treatment started 4 to approximately hours after the infection. No difference in the therapeutic effect of polymyxin B (PMB) and tetracycline (TC) administered via either im or iv route was found even in the delayed administration. In contrast to PMB and TC, lower toxicity of CLM was determined when it was administered iv rather than im."} {"id": "PMID:165331", "title": "Replication of Herpesvirus saimiri in cultured lymphocytes of infected owl monkeys (Aotus trivirgatus). An electron microscopic and immunofluorescent study.", "content": "The lymphocytes of five owl monkeys infected with Herpesvirus saimiri (HVS) and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture (AC). Buffy coats of whole blood immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died of malignant lymphoma and lymphocytic leukemia. HVS virions were demonstrated by electron microscopy and HVS antigens by immunofluorescence in 1 to 20 per cent of the lmyphocytes from infected monkeys in two of five cultures at 24 hours AC, four of five at 48 hours AC, and all five at 72 hours AC. There was quite good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained HVS virions or antigens. By electron microscopy the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Very seldom were enveloped virions observed. There was some evidence to suggest that the higher the percentage of lymphocytes containing HVS the poorer the prognosis for the monkey. HVS was isolated from all five infected monkeys by cocultivation of lymphocytes with Vero cells. Control lymphocyte cocultivations were negative.", "contents": "Replication of Herpesvirus saimiri in cultured lymphocytes of infected owl monkeys (Aotus trivirgatus). An electron microscopic and immunofluorescent study. The lymphocytes of five owl monkeys infected with Herpesvirus saimiri (HVS) and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture (AC). Buffy coats of whole blood immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died of malignant lymphoma and lymphocytic leukemia. HVS virions were demonstrated by electron microscopy and HVS antigens by immunofluorescence in 1 to 20 per cent of the lmyphocytes from infected monkeys in two of five cultures at 24 hours AC, four of five at 48 hours AC, and all five at 72 hours AC. There was quite good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained HVS virions or antigens. By electron microscopy the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Very seldom were enveloped virions observed. There was some evidence to suggest that the higher the percentage of lymphocytes containing HVS the poorer the prognosis for the monkey. HVS was isolated from all five infected monkeys by cocultivation of lymphocytes with Vero cells. Control lymphocyte cocultivations were negative."} {"id": "PMID:165332", "title": "Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.", "content": "Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.", "contents": "Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation. Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP."} {"id": "PMID:165333", "title": "Primary adenoid cystic carcinoma of the esophagus. Report of a case and review of the literature.", "content": "A case of primary adenoid cystic carcinoma of the esophagus is reported and a total of 15 cases was reviewed. There were 9 men, although earlier reports indicated the disease was more common in women. The lesion was located in the middle third of the esophagus in 10 cases. The possibility of tumor development from embryonal rests of the tracheobronchial tree in the esophagus is discussed. The prognosis of adenoid cystic carcinomas is not well known, but the treatment and prognosis appear similar to those of epidermoid carcinomas of the esophagus.", "contents": "Primary adenoid cystic carcinoma of the esophagus. Report of a case and review of the literature. A case of primary adenoid cystic carcinoma of the esophagus is reported and a total of 15 cases was reviewed. There were 9 men, although earlier reports indicated the disease was more common in women. The lesion was located in the middle third of the esophagus in 10 cases. The possibility of tumor development from embryonal rests of the tracheobronchial tree in the esophagus is discussed. The prognosis of adenoid cystic carcinomas is not well known, but the treatment and prognosis appear similar to those of epidermoid carcinomas of the esophagus."} {"id": "PMID:165334", "title": "Gluconeogenesis in isolated hepatic parenchymal cells. VII. Effects of monobutyryl cyclic adenosine monophosphate on gluconeogenic intermediates, phosphofructokinase, and fructose diphosphatase.", "content": "Isolated parenchymal hepatocytes prepared from fasted (24 hours) rats convert added dihydroxyacetone and xylitol to glucose. Monobutyryl cyclic adenosine-3',5'-mono-phosphate (mb-cAMP) stimulated the rate from dihydroxyacetone (plus 32%; N equals 28) but not from xylitol (plus 4%; N equals 27). Iodoacetate (0.15 to 0.20 mM) was an effective inhibitor of gluconeogenesis from lactate-pyruvate mixtures (72% inhibition); quinolinate (2.5 to 3.0 mM) was relatively ineffective (26% inhibition). Measurements of glucogenic intermediates formed from added dihydroxyacetone in hepatocytes (20% cell suspension) preincubated with iodoacetate provided evidence that phosphoglyceraldehyde dehydrogenase was inhibited. Inhibition of additional glycolytic-gluconeogenic enzyme(s) involved in dihydroxyacetone metabolism was not disclosed by the metabolite concentration data. Because iodoacetate partially inhibited gluconeogenesis from dihydroxyacetone in 5% cell suspensions but did not prevent stimulation of gluconeogenesis by mb-cAMP (plus 31%), additional inhibition, probably nonspecific, occurred. With dihydroxyacetone as substrate, mb-cAMP had only a slight effect on the concentration of fructose diphosphate (decrease) relative to control experiments (no mb-cAMP), but preinculation of the cells with iodoacetate made the mb-cAMP-induced decrease much greater. mb-cAMP caused a 47% decrease (SE, 8;N equals 9) in the assayable activity of phosphofructokinase in liver cells incubated with dihydroxyacetone but did not alter fructose diphosphatase activity significantly. Cyclic GMP and cIMP were shown to stimulate gluconeogenesis from dihydroxyacetone; both nucleotides also cause a decrease in the assayable activity of phosphofructokinase. With xylitol as substrate, mb-cAMP did not cause stimulation of gluconeogenesis, decrease in fructose diphosphate concentration, or decrease in phosphofructokinase activity. Our results indicate that phosphofructokinase might be an important controlling enzyme in gluconeogenesis and subject to regulation by cAMP.", "contents": "Gluconeogenesis in isolated hepatic parenchymal cells. VII. Effects of monobutyryl cyclic adenosine monophosphate on gluconeogenic intermediates, phosphofructokinase, and fructose diphosphatase. Isolated parenchymal hepatocytes prepared from fasted (24 hours) rats convert added dihydroxyacetone and xylitol to glucose. Monobutyryl cyclic adenosine-3',5'-mono-phosphate (mb-cAMP) stimulated the rate from dihydroxyacetone (plus 32%; N equals 28) but not from xylitol (plus 4%; N equals 27). Iodoacetate (0.15 to 0.20 mM) was an effective inhibitor of gluconeogenesis from lactate-pyruvate mixtures (72% inhibition); quinolinate (2.5 to 3.0 mM) was relatively ineffective (26% inhibition). Measurements of glucogenic intermediates formed from added dihydroxyacetone in hepatocytes (20% cell suspension) preincubated with iodoacetate provided evidence that phosphoglyceraldehyde dehydrogenase was inhibited. Inhibition of additional glycolytic-gluconeogenic enzyme(s) involved in dihydroxyacetone metabolism was not disclosed by the metabolite concentration data. Because iodoacetate partially inhibited gluconeogenesis from dihydroxyacetone in 5% cell suspensions but did not prevent stimulation of gluconeogenesis by mb-cAMP (plus 31%), additional inhibition, probably nonspecific, occurred. With dihydroxyacetone as substrate, mb-cAMP had only a slight effect on the concentration of fructose diphosphate (decrease) relative to control experiments (no mb-cAMP), but preinculation of the cells with iodoacetate made the mb-cAMP-induced decrease much greater. mb-cAMP caused a 47% decrease (SE, 8;N equals 9) in the assayable activity of phosphofructokinase in liver cells incubated with dihydroxyacetone but did not alter fructose diphosphatase activity significantly. Cyclic GMP and cIMP were shown to stimulate gluconeogenesis from dihydroxyacetone; both nucleotides also cause a decrease in the assayable activity of phosphofructokinase. With xylitol as substrate, mb-cAMP did not cause stimulation of gluconeogenesis, decrease in fructose diphosphate concentration, or decrease in phosphofructokinase activity. Our results indicate that phosphofructokinase might be an important controlling enzyme in gluconeogenesis and subject to regulation by cAMP."} {"id": "PMID:165335", "title": "Management of parotid gland tumors in infants and children.", "content": "Seventy-four pediatric patients with parotid gland tumors were seen during a 52-year period. Seventy percent of the lesions were benign and 30% were malignant. When the primary treatment is either subtotal or total parotidectomy, the recurrence rate was 2.3%. The facial nerve should be dissected free of parotid parenchyma and preserved, except if the lesion was malignant--a situation in which the nerve might have to be sacrificed totally or in part to ensure adequate tumor removal. No patient died of a benign or malignant lesion in this series, and the morbidity after surgical removal of primary tumors of the parotid gland in children and infants was low.", "contents": "Management of parotid gland tumors in infants and children. Seventy-four pediatric patients with parotid gland tumors were seen during a 52-year period. Seventy percent of the lesions were benign and 30% were malignant. When the primary treatment is either subtotal or total parotidectomy, the recurrence rate was 2.3%. The facial nerve should be dissected free of parotid parenchyma and preserved, except if the lesion was malignant--a situation in which the nerve might have to be sacrificed totally or in part to ensure adequate tumor removal. No patient died of a benign or malignant lesion in this series, and the morbidity after surgical removal of primary tumors of the parotid gland in children and infants was low."} {"id": "PMID:165343", "title": "Lipids of cultured hepatoma cells. VI. Glycerolipid and monoenoic fatty acid biosynthesis in minimal deviation hepatoma 7288C-1.", "content": "1-14C-Acetic, 1-14C-palmitic, or 1-14C-stearic acid was incubated with minimal deviation hepatoma 7288C cells grown in culture to assess: de novo fatty acid synthesis, oxidation, desaturation, and elongation of saturated fatty acids, as well as the ability of media fatty acids to serve as precursors of cellular glycerolipids. Distribution of radioactivity in the individual lipid classes and the various fatty acids of triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was determined. The radioactivity among the monoenoic acid isomers derived from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was analyzed by reductive ozonolysis. Only small amounts of the labeled substrates were oxidized to carbon dioxide. Except for labeled stearic acid, which also was incorporated heavily into phosphatidyl inositol and phosphatidyl serine, most radioactivity was recovered in triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine. Synthesis of cholesterol and long chain fatty acids from labeled acetic acid demonstrated that these cells can perform de novo synthesis of fatty acids and cholesterol. Both labeled palmitic and stearic acids were desaturated to the corresponding delta9 monoenes, and palmitic and palmitoleic acids were elongated. The nexadecenoic acid fraction isolated from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine, when acetic or palmitic acid was the labeled substrate, showed that greater than 70 percent of the labeled acids were the delta9 isomer. Radioactivity of the octadecenoic acid fraction derived from labeled acetic or palmitic acids was nearly equally divided between the delta9 isomer, oleic acid, and the delta11 isomer, vaccenic acid. Desaturation of labeled stearic acid produced only oleic acid. These data demonstrate that the biosynthesis of vaccenic acid in these cultured neoplastic cells proceeds via the elongation of palmitoleic acid. The relatively high level of vaccenic acid synthesis in these cells suggests that the reported elevation of \"oleic acid\" in many neoplasms may result from increased concentration of vaccenic acid.", "contents": "Lipids of cultured hepatoma cells. VI. Glycerolipid and monoenoic fatty acid biosynthesis in minimal deviation hepatoma 7288C-1. 1-14C-Acetic, 1-14C-palmitic, or 1-14C-stearic acid was incubated with minimal deviation hepatoma 7288C cells grown in culture to assess: de novo fatty acid synthesis, oxidation, desaturation, and elongation of saturated fatty acids, as well as the ability of media fatty acids to serve as precursors of cellular glycerolipids. Distribution of radioactivity in the individual lipid classes and the various fatty acids of triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was determined. The radioactivity among the monoenoic acid isomers derived from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine was analyzed by reductive ozonolysis. Only small amounts of the labeled substrates were oxidized to carbon dioxide. Except for labeled stearic acid, which also was incorporated heavily into phosphatidyl inositol and phosphatidyl serine, most radioactivity was recovered in triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine. Synthesis of cholesterol and long chain fatty acids from labeled acetic acid demonstrated that these cells can perform de novo synthesis of fatty acids and cholesterol. Both labeled palmitic and stearic acids were desaturated to the corresponding delta9 monoenes, and palmitic and palmitoleic acids were elongated. The nexadecenoic acid fraction isolated from triglyceride, phosphatidyl choline, and phosphatidyl ethanolamine, when acetic or palmitic acid was the labeled substrate, showed that greater than 70 percent of the labeled acids were the delta9 isomer. Radioactivity of the octadecenoic acid fraction derived from labeled acetic or palmitic acids was nearly equally divided between the delta9 isomer, oleic acid, and the delta11 isomer, vaccenic acid. Desaturation of labeled stearic acid produced only oleic acid. These data demonstrate that the biosynthesis of vaccenic acid in these cultured neoplastic cells proceeds via the elongation of palmitoleic acid. The relatively high level of vaccenic acid synthesis in these cells suggests that the reported elevation of \"oleic acid\" in many neoplasms may result from increased concentration of vaccenic acid."} {"id": "PMID:165344", "title": "Hepatoma, host liver, and normal rat liver neutral lipids as affected by diet.", "content": "Groups of normal and hepatoma (7288CTC) bearing rats were maintained on normal chow and fat-free diets for 4 weeks. Normal liver, host liver, and hepatoma neutral lipids were examined in detail and compared. Water content, unaffected by diet was: hepatoma, 82 percent; host liver, 71 percent; and normal liver, 67 percent. The fat-free diet had no effect upon the hepatoma neutral lipids but elevated the triglyceride level in normal and host liver, shifted the triglyceride carbon number distribution to lower mol wt, and elevated the percentage of monoenoic acids in triglycerides and cholesteryl esters. Host triglyceride concentrations were ca. half, and cholesterol levels were reduced moderately relative to normal liver values. Hepatoma cholesterol levels were higher and triglyceride concentrations lower than normal and host liver values. Hepatoma triglycerides differed dramatically from liver and were characterized by increased concentrations of high mol wt species and a fivefold increase in the percentage of C-20 and C-22 fatty acids. The percentage of C-20 and C-22 fatty acids in hepatoma cholesteryl esters also increased ca. fivefold relative to liver. The data indicate that the systems that regulate triglyceride and cholesteryl ester fatty acid composition in liver do not control the compositions of these lipid classes in this hepatoma. The unchanged high level of essential fatty acids in the hepatoma lipids from the fat-free fed animals demonstrates the hepatoma's ability to absorb and conserve specific fatty acids.", "contents": "Hepatoma, host liver, and normal rat liver neutral lipids as affected by diet. Groups of normal and hepatoma (7288CTC) bearing rats were maintained on normal chow and fat-free diets for 4 weeks. Normal liver, host liver, and hepatoma neutral lipids were examined in detail and compared. Water content, unaffected by diet was: hepatoma, 82 percent; host liver, 71 percent; and normal liver, 67 percent. The fat-free diet had no effect upon the hepatoma neutral lipids but elevated the triglyceride level in normal and host liver, shifted the triglyceride carbon number distribution to lower mol wt, and elevated the percentage of monoenoic acids in triglycerides and cholesteryl esters. Host triglyceride concentrations were ca. half, and cholesterol levels were reduced moderately relative to normal liver values. Hepatoma cholesterol levels were higher and triglyceride concentrations lower than normal and host liver values. Hepatoma triglycerides differed dramatically from liver and were characterized by increased concentrations of high mol wt species and a fivefold increase in the percentage of C-20 and C-22 fatty acids. The percentage of C-20 and C-22 fatty acids in hepatoma cholesteryl esters also increased ca. fivefold relative to liver. The data indicate that the systems that regulate triglyceride and cholesteryl ester fatty acid composition in liver do not control the compositions of these lipid classes in this hepatoma. The unchanged high level of essential fatty acids in the hepatoma lipids from the fat-free fed animals demonstrates the hepatoma's ability to absorb and conserve specific fatty acids."} {"id": "PMID:165345", "title": "Effects of diet and type IIa hyperlipoproteinemia upon structure of triacylglycerols and phosphatidyl cholines from human plasma lipoproteins.", "content": "Four normal and two individuals with Type IIa hyperlipoproteinemia were placed on the National Heart and Lung Institute Type IIa diet (low cholesterol, smaller than 300 mg/day, high polyunsaturated, low saturated fat diet) for 1 week and on a normal diet the following week. Plasma samples were obtained and the triacylglycerols, phospholipids, and cholesterol contents of plasma and of very low density lipoproteins, low density lipoproteins, and high density lipoproteins determined. Triacyglycerol fatty acid composition was determined and stereospecific analyses of triacglycerols and phosphatidyl cholines performed. Structural determinations were limited to one normal and one Type IIa individual. In normal and Type IIa individuals, chylomicrons contained twice the amount of 18:0 as did the very low density lipoproteins, low density lipoproteins, or high density lipoproteins. The structure of the triacyglycerols from the very low density lipoproteins and low density lipoproteins was asymmetric with at least 50M% 16:0 in the sn-1 position and mostly 18:1 in positions sn-2 and 3. There was a marked difference in the distribution of 18:2 in low density lipoproteins of the normal and Type IIa individuals. The control contained equal amounts of 18:2 in the sn-1 and sn-3 positions, whereas IIa low density lipoprotein was asymmetric with 26% of the 18:2 in position sn-1 and 3% in the sn-3 position. Very low density lipoprotein was asymmetric with regard to 18:2 in control and IIa samples with an average of 5% of the 18:2 in position sn-1 and 40% in position sn-3. The phosphatidyl cholines contained predominantly 16:0 and 18:0 in position sn-1, whereas the acids in position sn-2 were unsaturated with very little difference between lipoprotein classes. Neither the short dietary periods nor source of plasma affected the structure of the phosphatidyl cholines.", "contents": "Effects of diet and type IIa hyperlipoproteinemia upon structure of triacylglycerols and phosphatidyl cholines from human plasma lipoproteins. Four normal and two individuals with Type IIa hyperlipoproteinemia were placed on the National Heart and Lung Institute Type IIa diet (low cholesterol, smaller than 300 mg/day, high polyunsaturated, low saturated fat diet) for 1 week and on a normal diet the following week. Plasma samples were obtained and the triacylglycerols, phospholipids, and cholesterol contents of plasma and of very low density lipoproteins, low density lipoproteins, and high density lipoproteins determined. Triacyglycerol fatty acid composition was determined and stereospecific analyses of triacglycerols and phosphatidyl cholines performed. Structural determinations were limited to one normal and one Type IIa individual. In normal and Type IIa individuals, chylomicrons contained twice the amount of 18:0 as did the very low density lipoproteins, low density lipoproteins, or high density lipoproteins. The structure of the triacyglycerols from the very low density lipoproteins and low density lipoproteins was asymmetric with at least 50M% 16:0 in the sn-1 position and mostly 18:1 in positions sn-2 and 3. There was a marked difference in the distribution of 18:2 in low density lipoproteins of the normal and Type IIa individuals. The control contained equal amounts of 18:2 in the sn-1 and sn-3 positions, whereas IIa low density lipoprotein was asymmetric with 26% of the 18:2 in position sn-1 and 3% in the sn-3 position. Very low density lipoprotein was asymmetric with regard to 18:2 in control and IIa samples with an average of 5% of the 18:2 in position sn-1 and 40% in position sn-3. The phosphatidyl cholines contained predominantly 16:0 and 18:0 in position sn-1, whereas the acids in position sn-2 were unsaturated with very little difference between lipoprotein classes. Neither the short dietary periods nor source of plasma affected the structure of the phosphatidyl cholines."} {"id": "PMID:165346", "title": "Reaction of anti-phosphatidyl inositol antisera with neural membranes.", "content": "Ca. 15% of the phosphatidyl inositol in myelin and microsomal membranes from rat brain was detectable by antiphosphatidyl inositol antibody. Antibody-detectable phosphatidyl inositol in myelin and microsomes readily increased when the membranes were incubated at 45 C with the antiserum. Synaptic membranes also had only a limited capacity to adsorb antibody. Quantitative binding studies with synaptic membranes and mitochondria were limited, because these membranes contain cardiolipin, which cross reacts with phosphatidyl inositol antisera. Moreover, highly purified synaptic and mitochondrial membranes contain appreciable amounts of other membrane fractions.", "contents": "Reaction of anti-phosphatidyl inositol antisera with neural membranes. Ca. 15% of the phosphatidyl inositol in myelin and microsomal membranes from rat brain was detectable by antiphosphatidyl inositol antibody. Antibody-detectable phosphatidyl inositol in myelin and microsomes readily increased when the membranes were incubated at 45 C with the antiserum. Synaptic membranes also had only a limited capacity to adsorb antibody. Quantitative binding studies with synaptic membranes and mitochondria were limited, because these membranes contain cardiolipin, which cross reacts with phosphatidyl inositol antisera. Moreover, highly purified synaptic and mitochondrial membranes contain appreciable amounts of other membrane fractions."} {"id": "PMID:165350", "title": "Site of free-fatty-acid inhibition of lipolysis by human adipocytes.", "content": "When human adipocytes were incubated in albumin-free buffer, isoproterenol failed to stimulate an increase in either cyclic AMP or glycerol release. Cells incubated for 1/2 hr with 4% albumin and isoproterenol had a striking increase in cyclic AMP; this effect was markedly reduced when FFA concentration was increased by the addition of sodium oleate. When incubation was prolonged to 4 hr, the cyclic AMP concentration of stimulated cells fell towards the basal level. This decline in the level of cyclic AMP was prevented by frequent change in buffer. The ability of epinephrine and sodium fluoride to stimulate the adenylyl cyclase of human adipocyte membranes was not affected by the addition of sodium oleate. However, when intact cells were preincubated for 1 hr with added sodium oleate, the responsiveness to epinephrine of membranes derived from the cells was reduced. No such alternation in responsiveness to sodium fluoride occurred. These results indicate that the inhibitory effect of FFA on lipolysis is associated with a reduced production of cyclic AMP; the latter effect may be the consequence of FFA inhibition of adenylyl cyclase.", "contents": "Site of free-fatty-acid inhibition of lipolysis by human adipocytes. When human adipocytes were incubated in albumin-free buffer, isoproterenol failed to stimulate an increase in either cyclic AMP or glycerol release. Cells incubated for 1/2 hr with 4% albumin and isoproterenol had a striking increase in cyclic AMP; this effect was markedly reduced when FFA concentration was increased by the addition of sodium oleate. When incubation was prolonged to 4 hr, the cyclic AMP concentration of stimulated cells fell towards the basal level. This decline in the level of cyclic AMP was prevented by frequent change in buffer. The ability of epinephrine and sodium fluoride to stimulate the adenylyl cyclase of human adipocyte membranes was not affected by the addition of sodium oleate. However, when intact cells were preincubated for 1 hr with added sodium oleate, the responsiveness to epinephrine of membranes derived from the cells was reduced. No such alternation in responsiveness to sodium fluoride occurred. These results indicate that the inhibitory effect of FFA on lipolysis is associated with a reduced production of cyclic AMP; the latter effect may be the consequence of FFA inhibition of adenylyl cyclase."} {"id": "PMID:165351", "title": "Biphasic effect of the alpha-adrenolytic phentolamine on hormone-stimulated formation of cyclic adenosine-3',5'-monophosphate in isolated fat cells of rats.", "content": "Isolated fat cells from rat epididymal adipose tissue were incubated with various lipolytic hormones in the absence and presence of the alpha-adrenergic blocking agent phentolamine. Lipolysis, stimulated by noradrenaline, isoproterenol, or ACTH, was inhibited dose-dependently by phentolamine. At concentrations of phentolamine where lipolysis was already inhibited, phentolamine had a biphasic effect on hormone-stimulated formation of cAMP. Low concentrations of phentolamine enhanced cAMP formation, while high concentrations inhibited cAMP. The additional increase of cAMP formation by phentolamine was only seen with maximally effective concentrations of noradrenaline, isoproterenol, and ACTH. Half-maximally effective concentrations were invariably inhibited by phentolamine. The activity of noradrenaline-stimulated adenylate cyclase of fat-cell plasma membranes was inhibited by phentolamine, whereas cAMP phosphodiesterase activity was unaffected.", "contents": "Biphasic effect of the alpha-adrenolytic phentolamine on hormone-stimulated formation of cyclic adenosine-3',5'-monophosphate in isolated fat cells of rats. Isolated fat cells from rat epididymal adipose tissue were incubated with various lipolytic hormones in the absence and presence of the alpha-adrenergic blocking agent phentolamine. Lipolysis, stimulated by noradrenaline, isoproterenol, or ACTH, was inhibited dose-dependently by phentolamine. At concentrations of phentolamine where lipolysis was already inhibited, phentolamine had a biphasic effect on hormone-stimulated formation of cAMP. Low concentrations of phentolamine enhanced cAMP formation, while high concentrations inhibited cAMP. The additional increase of cAMP formation by phentolamine was only seen with maximally effective concentrations of noradrenaline, isoproterenol, and ACTH. Half-maximally effective concentrations were invariably inhibited by phentolamine. The activity of noradrenaline-stimulated adenylate cyclase of fat-cell plasma membranes was inhibited by phentolamine, whereas cAMP phosphodiesterase activity was unaffected."} {"id": "PMID:165352", "title": "The glucagon receptor and adenylate cyclase.", "content": "Acidic phospholipids play a critical role in the hormone activation of adenylate cyclase. Solubilized myocardial adenylate cyclase is unresponsive to glucagon and the catecholamines, two of the hormones which activate the membrane-bound enzyme. Phosphatidylserine, purified from bovine brain restored glucagon responsiveness of the solubilized adenylate cyclase. Monophosphatidylinositol, also purified from bovine brain, restored catecholamine responsiveness. Solubilized preparations of myocardial adenylate cyclase bind 125-I-glucagon either in the presence of added phosphatidylserine, thereby providing a clear separation of the processes of activation and binding. Solubilized myocardial adenylate cyclase has a molecular weight of about 160,000. Sephadex G-100 chromatography of the solubilized enzyme following the binding of 125-I-glucagon to its myocardial receptor reveals two distinct peaks; one, having catalytic activity and a molecular weight greater than 100,000 and two, the binding material having no catalytic activity and a molecular weight of 24,000-28,000. These data are consistent with the presence of a dissociable glucagon receptor site. The role of this dissociation in the activation-inactivation of the enzyme remains to be explored. It is postulated that phospholipids induce the required configurational change in the catalytic site following the binding of hormone to its receptor, and by this means couples the receptor to the catalytic site. This model may be applicable to certain clinical situations. Cardiac adenylate cyclase is unresponsive to glucagon in chronic congestive heart failure. The defect may reside either in the binding of glucagon to its receptor site or in the metabolism of a specific acidic phospholipid such as phosphatidylserine.", "contents": "The glucagon receptor and adenylate cyclase. Acidic phospholipids play a critical role in the hormone activation of adenylate cyclase. Solubilized myocardial adenylate cyclase is unresponsive to glucagon and the catecholamines, two of the hormones which activate the membrane-bound enzyme. Phosphatidylserine, purified from bovine brain restored glucagon responsiveness of the solubilized adenylate cyclase. Monophosphatidylinositol, also purified from bovine brain, restored catecholamine responsiveness. Solubilized preparations of myocardial adenylate cyclase bind 125-I-glucagon either in the presence of added phosphatidylserine, thereby providing a clear separation of the processes of activation and binding. Solubilized myocardial adenylate cyclase has a molecular weight of about 160,000. Sephadex G-100 chromatography of the solubilized enzyme following the binding of 125-I-glucagon to its myocardial receptor reveals two distinct peaks; one, having catalytic activity and a molecular weight greater than 100,000 and two, the binding material having no catalytic activity and a molecular weight of 24,000-28,000. These data are consistent with the presence of a dissociable glucagon receptor site. The role of this dissociation in the activation-inactivation of the enzyme remains to be explored. It is postulated that phospholipids induce the required configurational change in the catalytic site following the binding of hormone to its receptor, and by this means couples the receptor to the catalytic site. This model may be applicable to certain clinical situations. Cardiac adenylate cyclase is unresponsive to glucagon in chronic congestive heart failure. The defect may reside either in the binding of glucagon to its receptor site or in the metabolism of a specific acidic phospholipid such as phosphatidylserine."} {"id": "PMID:165353", "title": "The role of cyclic GMP in the regulation of cyclic AMP hydrolysis.", "content": "A rat-heart cyclic nucleotide phosphodiesterase has been chromatographically separated from related enzymes and its kinetic properties have been studied. The enzyme can hydrolyze both cyclic AMP and cyclic GMP and has about the same maximum velocity and apparent KM (greater than 10-5 M) for the two nucleotides. Kinetic plots indicate positive cooperative behavior for both substrates. Cyclic GMP at low concentrations is a potent activator of cyclic AMP hydrolysis and this activation, as well as the cooperativity, can be abolished by treatment with solvents or sulfydryl reagents under conditions which do not destroy the catalytic function. A kinetic model for this enzyme is porposed and the physiologic role is discussed.", "contents": "The role of cyclic GMP in the regulation of cyclic AMP hydrolysis. A rat-heart cyclic nucleotide phosphodiesterase has been chromatographically separated from related enzymes and its kinetic properties have been studied. The enzyme can hydrolyze both cyclic AMP and cyclic GMP and has about the same maximum velocity and apparent KM (greater than 10-5 M) for the two nucleotides. Kinetic plots indicate positive cooperative behavior for both substrates. Cyclic GMP at low concentrations is a potent activator of cyclic AMP hydrolysis and this activation, as well as the cooperativity, can be abolished by treatment with solvents or sulfydryl reagents under conditions which do not destroy the catalytic function. A kinetic model for this enzyme is porposed and the physiologic role is discussed."} {"id": "PMID:165354", "title": "Divergent actions of protein kinase modulator in regulating mammalian cyclic GMP-dependent and cyclic AMP-dependent protein kinases.", "content": "Protein kinase modulator can either augment or depress phosphorylation of substrate proteins catalyzed by cyclic GMP-dependent and cyclic AMP-dependent protein kinases prepared from mammalian and arthropod tissues. Alteration by the modulator of the phosphorylating activity of the protein kinases is considered to be due to modification of protein substrate specificity subsequent to interaction of the modulator with the catalytic subunits of the enzymes. It is likely that the physiologic role of the modulator is to monitor the opposing effects of cyclic GMP and cyclic AMP by regulating the activity of respective protein kinases. Thus the modulator may function as a biologic \"fine tuner\" providing on additional mechanism by which the signals imparted to cells by physiologic stimuli can be correctly expressed.", "contents": "Divergent actions of protein kinase modulator in regulating mammalian cyclic GMP-dependent and cyclic AMP-dependent protein kinases. Protein kinase modulator can either augment or depress phosphorylation of substrate proteins catalyzed by cyclic GMP-dependent and cyclic AMP-dependent protein kinases prepared from mammalian and arthropod tissues. Alteration by the modulator of the phosphorylating activity of the protein kinases is considered to be due to modification of protein substrate specificity subsequent to interaction of the modulator with the catalytic subunits of the enzymes. It is likely that the physiologic role of the modulator is to monitor the opposing effects of cyclic GMP and cyclic AMP by regulating the activity of respective protein kinases. Thus the modulator may function as a biologic \"fine tuner\" providing on additional mechanism by which the signals imparted to cells by physiologic stimuli can be correctly expressed."} {"id": "PMID:165355", "title": "Widespread occurrence of a specific protein in vertebrate tissues and regulation by cyclic AMP of its endogenous phosphorylation and dephosphorylation.", "content": "A protein whose endogenous phosphorylation and dephosphorylation are affected by cAMP has been found in the soluble and particulate fractions of all vertebrate tissues studied. This phosphoprotein, which contained a substantial proportion of the radioactive phosphate observed on SDS-polyacrylamide gels, was estimated to have an apparent molecular weight of 49,000. In the presence of Zn++, cAMP inhibited the endogenous phosphorylation of this protein (protein 49) in the cytosol and microsomal fractions. In the presence of Mg++, cAMP stimulated the phosphorylation of protein 49 in the cytosol fractions, but had only slight effects in the microsomal fractions. The dephosphorylation of protein 49 by an endogenous protein phosphatase was markedly stimulated by cAMP in the cytosol and microsomal fractions of all tissues studied. The binding of 8-azido-cAMP (a photoaffinity analog of cAMP, which reacts specifically with cAMP-binding sites) to subcellular fractions was also studied. This binding was principally to a protein of molecular weight 49,000. These and other data suggest that a cAMP-binding protein with a molecular weight of 49,000 capable of undergoing cAMP-dependent phosphorylation and dephosphorylation, occurs in a variety of tissues.", "contents": "Widespread occurrence of a specific protein in vertebrate tissues and regulation by cyclic AMP of its endogenous phosphorylation and dephosphorylation. A protein whose endogenous phosphorylation and dephosphorylation are affected by cAMP has been found in the soluble and particulate fractions of all vertebrate tissues studied. This phosphoprotein, which contained a substantial proportion of the radioactive phosphate observed on SDS-polyacrylamide gels, was estimated to have an apparent molecular weight of 49,000. In the presence of Zn++, cAMP inhibited the endogenous phosphorylation of this protein (protein 49) in the cytosol and microsomal fractions. In the presence of Mg++, cAMP stimulated the phosphorylation of protein 49 in the cytosol fractions, but had only slight effects in the microsomal fractions. The dephosphorylation of protein 49 by an endogenous protein phosphatase was markedly stimulated by cAMP in the cytosol and microsomal fractions of all tissues studied. The binding of 8-azido-cAMP (a photoaffinity analog of cAMP, which reacts specifically with cAMP-binding sites) to subcellular fractions was also studied. This binding was principally to a protein of molecular weight 49,000. These and other data suggest that a cAMP-binding protein with a molecular weight of 49,000 capable of undergoing cAMP-dependent phosphorylation and dephosphorylation, occurs in a variety of tissues."} {"id": "PMID:165356", "title": "Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells.", "content": "The characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed.", "contents": "Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells. The characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed."} {"id": "PMID:165357", "title": "Studies on cyclic AMP metabolism in human epidermoid carcinoma (HEp-2) cells.", "content": "Cultured human epidermoid carcinoma (HEp-2) cells were found to contain a highly responsive, catecholamine-sensitive adenyl cyclase activity in cellfree preparations. By contrast, cyclic AMP levels in intact HEp-2 cells were at best only marginally increased by catecholamines under a variety of conditions. The lack of an intact cell response could not be accounted for by escape of cyclic AMP to the medium, excessive phosphodiesterase activity, inactivation of the catecholamine, or by unusual kinetics of the system. However, in the presence of 1-methyl,3-iso-butylxanthine (MIX), a potent phosphodiesterase inhibitor, a moderate catecholamine response was observed in the intact cells. A significant elevation of cyclic AMP levels in the presence of MIX was observed at 0.3 muM epinephrine, and maximal levels occurred at 10 muM. Norepinephrine was much less effective than either epinephrine or isopropylnorepinephrine at 10 muM concentrations. In addition, intact cells slowly but steadily released cyclic AMP into the incubation medium over the course of 60-min incubations in the presence of MIX and epinephrine; maximum intracellular levels were reached by 5 min.", "contents": "Studies on cyclic AMP metabolism in human epidermoid carcinoma (HEp-2) cells. Cultured human epidermoid carcinoma (HEp-2) cells were found to contain a highly responsive, catecholamine-sensitive adenyl cyclase activity in cellfree preparations. By contrast, cyclic AMP levels in intact HEp-2 cells were at best only marginally increased by catecholamines under a variety of conditions. The lack of an intact cell response could not be accounted for by escape of cyclic AMP to the medium, excessive phosphodiesterase activity, inactivation of the catecholamine, or by unusual kinetics of the system. However, in the presence of 1-methyl,3-iso-butylxanthine (MIX), a potent phosphodiesterase inhibitor, a moderate catecholamine response was observed in the intact cells. A significant elevation of cyclic AMP levels in the presence of MIX was observed at 0.3 muM epinephrine, and maximal levels occurred at 10 muM. Norepinephrine was much less effective than either epinephrine or isopropylnorepinephrine at 10 muM concentrations. In addition, intact cells slowly but steadily released cyclic AMP into the incubation medium over the course of 60-min incubations in the presence of MIX and epinephrine; maximum intracellular levels were reached by 5 min."} {"id": "PMID:165358", "title": "Phosphorylase kinase mediating the effects of cyclic AMP in muscle.", "content": "In the classic view of the control of phosphorylase b to a conversion by catecholamines, cyclic AMP acts as the second messenger stimulating the activity of cyclic AMP-dependent protein kinase to covalently modify phosphorylase kinase. Phosphorylation of phosphorylase kinase converts this enzyme form with a nonactivated to an activated form with a markedly higher activity at pH 7. There is now considerable evidence that the activity of phospphorylase kinase is also regulated by changeds in the Ca-2+ concentration. The activity of both nonactivated and activated phosphorylase kinase is stimulated by Ca-2+ in the range of concentrations that have been reported to occur in the sacroplasm of contracting muscle, with the activated pphosphorylase kinase having a lower K-alpha for Ca-2+. Thus there are at leaset two mechanisms for the regulation of phosphorylase kinase activity in muscle. These mechanisms may act independently or in concert in controlling glycogenolysis stimulated by catecholamines, anoxia, or tetanic electrical stimulation...", "contents": "Phosphorylase kinase mediating the effects of cyclic AMP in muscle. In the classic view of the control of phosphorylase b to a conversion by catecholamines, cyclic AMP acts as the second messenger stimulating the activity of cyclic AMP-dependent protein kinase to covalently modify phosphorylase kinase. Phosphorylation of phosphorylase kinase converts this enzyme form with a nonactivated to an activated form with a markedly higher activity at pH 7. There is now considerable evidence that the activity of phospphorylase kinase is also regulated by changeds in the Ca-2+ concentration. The activity of both nonactivated and activated phosphorylase kinase is stimulated by Ca-2+ in the range of concentrations that have been reported to occur in the sacroplasm of contracting muscle, with the activated pphosphorylase kinase having a lower K-alpha for Ca-2+. Thus there are at leaset two mechanisms for the regulation of phosphorylase kinase activity in muscle. These mechanisms may act independently or in concert in controlling glycogenolysis stimulated by catecholamines, anoxia, or tetanic electrical stimulation..."} {"id": "PMID:165359", "title": "Thyroid-stimulating hormone and cyclic adenosine 3',5'-monophosphate in the regulation of thyroid gland function.", "content": "The initial step in TSH action reflects binding of the hormone to specific receptor sites on the plasma membrane. Such binding has been studied using plasma membranes, homogenates, isolated thyroid cells grown in culture, and thyroid slices. 3-H- and iodinated TSH preparations have been used; the latter have been prepared using both chloramine-T and lactoperoxidase. Some of the discrepancies reported in the literature might reflect the different thyroid and hormone preparations and the variable incubation conditions which have been used. In general, good correlation exists between binding of TSH and activation of adenylate cyclase in thyroid plasma membranes. Data is reviewed related to activation of protein kinase in intact thyroid cells by TSH. Although there is impressive evidence for cyclic AMP mediation of effects of TSH on the thyroid, some data that are inconsistent with this concept are considered, especially in relationship to 32-P incorporation into phospholipid. The role of cyclic GMP in thyroid function is discussed.", "contents": "Thyroid-stimulating hormone and cyclic adenosine 3',5'-monophosphate in the regulation of thyroid gland function. The initial step in TSH action reflects binding of the hormone to specific receptor sites on the plasma membrane. Such binding has been studied using plasma membranes, homogenates, isolated thyroid cells grown in culture, and thyroid slices. 3-H- and iodinated TSH preparations have been used; the latter have been prepared using both chloramine-T and lactoperoxidase. Some of the discrepancies reported in the literature might reflect the different thyroid and hormone preparations and the variable incubation conditions which have been used. In general, good correlation exists between binding of TSH and activation of adenylate cyclase in thyroid plasma membranes. Data is reviewed related to activation of protein kinase in intact thyroid cells by TSH. Although there is impressive evidence for cyclic AMP mediation of effects of TSH on the thyroid, some data that are inconsistent with this concept are considered, especially in relationship to 32-P incorporation into phospholipid. The role of cyclic GMP in thyroid function is discussed."} {"id": "PMID:165360", "title": "Cyclic nucleotides and gluconeogenesis by rat liver cells.", "content": "Gluconeogenesis from lactate, pyruvate, fructose, alanine, and other substrates was accelerated by glucagon or epinephrine in hepatocytes isolated from rat liver. Glucagon and epinephrine also increased cyclic AMP accumulation by rat hepatocytes. Isoproterenol increased cyclic AMP but not gluconeogenesis, while phenylephrine accelerated gluconeogenesis. The activation of gluconeogenesis by epinephrine was unaffected by propranolol but blocked by dihydroergotamine. Dibutyryl cyclic AMP added to hepatocytes stimulated gluconeogenesis at concentrations as low as 1 muM. Exogenous cyclic GMP (0.1- muM) inhibited gluconeogenesis due to either glucagon or epinephrine without affecting basal gluconeogenesis. However, carbamylcholine did not affect gluconeogenesis by hepatocytes. Basal gluconeogenesis and the increases due to all agents were inhibited by removal of extracellular calcium or the presence of A-23187, D-600, or tetracaine. In contrast, added 0.1 muM cyclic GMP, 2 mM NH-4-Cl, and 10 muM phenethylbiguanide inhibited glucagon- or epinephrine-stimulated gluconeogenesis without affecting basal values. Studies with hepatocytes indicate that the hormonal activation of gluconeogenesis is not limited to substrates entering prior to triose phosphate formation. Glucagon may act by increasing cyclic AMP which acts via unknown mechanisms to increase gluconeogenesis. In contrast, epinephrine acts via a cyclic AMP-independent mechamism which does not appear to involve cyclic GMP, Ca-2+ flux, of K+ flux.", "contents": "Cyclic nucleotides and gluconeogenesis by rat liver cells. Gluconeogenesis from lactate, pyruvate, fructose, alanine, and other substrates was accelerated by glucagon or epinephrine in hepatocytes isolated from rat liver. Glucagon and epinephrine also increased cyclic AMP accumulation by rat hepatocytes. Isoproterenol increased cyclic AMP but not gluconeogenesis, while phenylephrine accelerated gluconeogenesis. The activation of gluconeogenesis by epinephrine was unaffected by propranolol but blocked by dihydroergotamine. Dibutyryl cyclic AMP added to hepatocytes stimulated gluconeogenesis at concentrations as low as 1 muM. Exogenous cyclic GMP (0.1- muM) inhibited gluconeogenesis due to either glucagon or epinephrine without affecting basal gluconeogenesis. However, carbamylcholine did not affect gluconeogenesis by hepatocytes. Basal gluconeogenesis and the increases due to all agents were inhibited by removal of extracellular calcium or the presence of A-23187, D-600, or tetracaine. In contrast, added 0.1 muM cyclic GMP, 2 mM NH-4-Cl, and 10 muM phenethylbiguanide inhibited glucagon- or epinephrine-stimulated gluconeogenesis without affecting basal values. Studies with hepatocytes indicate that the hormonal activation of gluconeogenesis is not limited to substrates entering prior to triose phosphate formation. Glucagon may act by increasing cyclic AMP which acts via unknown mechanisms to increase gluconeogenesis. In contrast, epinephrine acts via a cyclic AMP-independent mechamism which does not appear to involve cyclic GMP, Ca-2+ flux, of K+ flux."} {"id": "PMID:165361", "title": "The role of calcium and cyclic nucleotides in alpha-amylase release from slices of rat parotid: studies with the divalent cation ionophore A-23187.", "content": "The divalent cation ionophore A-23187 caused a Ca-2+-dependent increase in alpha-amylase release from slices of rat parotid gland. The effect of A-23187 on alpha-amylase release was not caused by release of endogenous agonists since l-propranolol, phentolamine, and atropine had no effect. The magnitude of alpha-amylase release caused by A-23187 was small compared to the effect of isoproterenol. In this respect it more closely resembles the action of cholinergic and alpha-adrenergic agonists on alpha-amylase release. A-23187 inhibited the increase in the level of parotid adenosine 3,5'-monophosphate caused by isoprotrenol. The inhibitory effect required incubation of the slices with the ionophore before the addition of isoproterenol. The ionophore also caused a Ca-2+-dependent increase in the level of guanosine 3',5'-monophosphate (cyclic GMP). Theophylline enhanced the effect of A-23187 on the level of cyclic GMP. These results emphasize the role of Ca-2+ in the regulation of parotid cyclic nucleotide levels. Since the effects of the ionophore depended on the presence of Ca-2+, it is possible that some of the effects of agonists on parotid gland physiology are secondary to an action on intracellular Ca-2+ distribution.", "contents": "The role of calcium and cyclic nucleotides in alpha-amylase release from slices of rat parotid: studies with the divalent cation ionophore A-23187. The divalent cation ionophore A-23187 caused a Ca-2+-dependent increase in alpha-amylase release from slices of rat parotid gland. The effect of A-23187 on alpha-amylase release was not caused by release of endogenous agonists since l-propranolol, phentolamine, and atropine had no effect. The magnitude of alpha-amylase release caused by A-23187 was small compared to the effect of isoproterenol. In this respect it more closely resembles the action of cholinergic and alpha-adrenergic agonists on alpha-amylase release. A-23187 inhibited the increase in the level of parotid adenosine 3,5'-monophosphate caused by isoprotrenol. The inhibitory effect required incubation of the slices with the ionophore before the addition of isoproterenol. The ionophore also caused a Ca-2+-dependent increase in the level of guanosine 3',5'-monophosphate (cyclic GMP). Theophylline enhanced the effect of A-23187 on the level of cyclic GMP. These results emphasize the role of Ca-2+ in the regulation of parotid cyclic nucleotide levels. Since the effects of the ionophore depended on the presence of Ca-2+, it is possible that some of the effects of agonists on parotid gland physiology are secondary to an action on intracellular Ca-2+ distribution."} {"id": "PMID:165362", "title": "Cyclic AMP and cyclic GMP: studies utilizing immunohistochemical techniques for the localization of the nucleotides in tissue.", "content": "Antibodies to the cyclic nucleotides initially were utilized in radioimmunoassays for cyclic AMP and cyclic GMP which might be present in mammalian tissues. allowed measurement of the nucleotides on small amounts of tissue in physiologic studies. To gain further insight into the relative roles of cyclic AMP and cyclic GMP in cell function, these antibodies have been applied to immunohistochemical studies for the localization of the cyclic nucleotides in tissues and cells. This methodology is useful for determining in which cell type in a heterogeneous tissue increases in cyclic nucleotide concentrations occur. In addition, within individual cells, staining patterns for cyclic AMP and cyclic GMP are usually quite distinct. Cyclic GMP in canine thyroid is located to the follicular cell membrane while cyclic AMP is ubiquitously distributed in follicular cell cytoplasm. In both rat adrenal cortex and testis, there is prominent nuclear localization of cyclic GMP, suggesting a role for the nucleotide in growth regulation. These studies provide histologic evidence suggesting diverse roles for cyclic AMP and cyclic GMP in mammalian physiology. It is anticipated that this technique will also be useful in the ultrastructural localization of the cyclic nucleotides and for the identification of other cyclic nucleotides which might be present in mammalian tissues.", "contents": "Cyclic AMP and cyclic GMP: studies utilizing immunohistochemical techniques for the localization of the nucleotides in tissue. Antibodies to the cyclic nucleotides initially were utilized in radioimmunoassays for cyclic AMP and cyclic GMP which might be present in mammalian tissues. allowed measurement of the nucleotides on small amounts of tissue in physiologic studies. To gain further insight into the relative roles of cyclic AMP and cyclic GMP in cell function, these antibodies have been applied to immunohistochemical studies for the localization of the cyclic nucleotides in tissues and cells. This methodology is useful for determining in which cell type in a heterogeneous tissue increases in cyclic nucleotide concentrations occur. In addition, within individual cells, staining patterns for cyclic AMP and cyclic GMP are usually quite distinct. Cyclic GMP in canine thyroid is located to the follicular cell membrane while cyclic AMP is ubiquitously distributed in follicular cell cytoplasm. In both rat adrenal cortex and testis, there is prominent nuclear localization of cyclic GMP, suggesting a role for the nucleotide in growth regulation. These studies provide histologic evidence suggesting diverse roles for cyclic AMP and cyclic GMP in mammalian physiology. It is anticipated that this technique will also be useful in the ultrastructural localization of the cyclic nucleotides and for the identification of other cyclic nucleotides which might be present in mammalian tissues."} {"id": "PMID:165363", "title": "Effects of norepinephrine on cyclic nucleotide levels in the ductus deferens of the rat.", "content": "The effect of 1-norepinephrine on cyclic nucleotide levels was studied in rat ductus deferens. Norepinephrine (0.01-0.3 mM) increased cyclic AMP and cyclic GMP levels in a concentration-dependent manner. Cyclic GMP was increased by about two-fold and cyclic AMP by 30%-40% by 0.1 mM norepinephrine after 3 min. Phenylephrine (0.1 mM) increased cyclic GMP levels about twofold without affecting cyclic AMP. Cyclic GMP was maximally increased by norepinephrine or phenylephrine after 3-10 min, but was not significantly changed after 20 sec, when contraction was fully developed. Atropine did not affect the norepinephrine-induced changes in cyclic nucleotide levels; phentolamine blocked the effect of norepinephrine on cyclic GMP, and propanolol blocked that on cyclic AMP. These findings indicate that in the ductus deferens alpha-adrenergic receptors are involved in the effect of catecholamines on cyclic GMP, and beta-adrenergic receptors are involved in the effect on cyclic AMP levels. The presence of Ca-2+ was required for the effect of norepinephrine on cyclic GMP, but not on cyclic AMP.", "contents": "Effects of norepinephrine on cyclic nucleotide levels in the ductus deferens of the rat. The effect of 1-norepinephrine on cyclic nucleotide levels was studied in rat ductus deferens. Norepinephrine (0.01-0.3 mM) increased cyclic AMP and cyclic GMP levels in a concentration-dependent manner. Cyclic GMP was increased by about two-fold and cyclic AMP by 30%-40% by 0.1 mM norepinephrine after 3 min. Phenylephrine (0.1 mM) increased cyclic GMP levels about twofold without affecting cyclic AMP. Cyclic GMP was maximally increased by norepinephrine or phenylephrine after 3-10 min, but was not significantly changed after 20 sec, when contraction was fully developed. Atropine did not affect the norepinephrine-induced changes in cyclic nucleotide levels; phentolamine blocked the effect of norepinephrine on cyclic GMP, and propanolol blocked that on cyclic AMP. These findings indicate that in the ductus deferens alpha-adrenergic receptors are involved in the effect of catecholamines on cyclic GMP, and beta-adrenergic receptors are involved in the effect on cyclic AMP levels. The presence of Ca-2+ was required for the effect of norepinephrine on cyclic GMP, but not on cyclic AMP."} {"id": "PMID:165364", "title": "Modulation of human neutrophil chemotactic responses by cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate.", "content": "Cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) and compounds known to effect the intracellular concentrations of these nucleotides were examined for their ability to effect human neutrophil (PMN) responsiveness to chemotactic stimulation. Incubation of neutrophils with agents recognized to promote increases in intracellular cAMP in a variety of tissues (i.e., epinephrine, norepinephrine, isoproterenol, histamine, cholera toxin, and prostaglandin E-1 and E-2) or with cAMP inhibited the leukotactic response to a bacterial chemotactic factor. In contrast, cGMP and compounds which have been shown to promote increases in intracellular cGMP concentration (i.e., acetylcholine, carbamylcholine, phorbol myristate acetate, and prostaglindin F-2-alpha) markedly enhanced the neutrophil chemotactic response. The inhibitory or stimulatory influences on chemotactic responsiveness promoted by several of the agents could be shown to be blocked by a specific pharmacologic antagonist of the particular compound tested. These data support the hypothesis that cGMP and cAMP can provide opposing regulatory influences on certain cellular functions; in this case, directed motility of leukocytes.", "contents": "Modulation of human neutrophil chemotactic responses by cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate. Cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) and compounds known to effect the intracellular concentrations of these nucleotides were examined for their ability to effect human neutrophil (PMN) responsiveness to chemotactic stimulation. Incubation of neutrophils with agents recognized to promote increases in intracellular cAMP in a variety of tissues (i.e., epinephrine, norepinephrine, isoproterenol, histamine, cholera toxin, and prostaglandin E-1 and E-2) or with cAMP inhibited the leukotactic response to a bacterial chemotactic factor. In contrast, cGMP and compounds which have been shown to promote increases in intracellular cGMP concentration (i.e., acetylcholine, carbamylcholine, phorbol myristate acetate, and prostaglindin F-2-alpha) markedly enhanced the neutrophil chemotactic response. The inhibitory or stimulatory influences on chemotactic responsiveness promoted by several of the agents could be shown to be blocked by a specific pharmacologic antagonist of the particular compound tested. These data support the hypothesis that cGMP and cAMP can provide opposing regulatory influences on certain cellular functions; in this case, directed motility of leukocytes."} {"id": "PMID:165365", "title": "The mechanism of the potentiating effect of glucocorticoids on catecholamine-induced lipolysis.", "content": "Preincubation of isolated epididymal fat cells with dexamethasone or treating rats with cortisol enhances the epinephrine-stimulated lipolysis of the cells as well as cAMP-dependent protein kinase activity in homogenates of these fat cell suspensions. During maximal inhibition of phosphodiesterase activity by theophylline or dibutyryl cAMP, this potentiating effect of glucocorticoids on the fat cells was also present. There was no lowering of the total phosphodiesterase activity in homogenates of fat cell suspensions of rats that were treated with cortisol, but there appeared to be a lower activity of the low KM phosphodiesterase activity. It is concluded that induction of protein kinase by glucocorticoid hormone is responsible for its special type of stimulative action on lipolysis.", "contents": "The mechanism of the potentiating effect of glucocorticoids on catecholamine-induced lipolysis. Preincubation of isolated epididymal fat cells with dexamethasone or treating rats with cortisol enhances the epinephrine-stimulated lipolysis of the cells as well as cAMP-dependent protein kinase activity in homogenates of these fat cell suspensions. During maximal inhibition of phosphodiesterase activity by theophylline or dibutyryl cAMP, this potentiating effect of glucocorticoids on the fat cells was also present. There was no lowering of the total phosphodiesterase activity in homogenates of fat cell suspensions of rats that were treated with cortisol, but there appeared to be a lower activity of the low KM phosphodiesterase activity. It is concluded that induction of protein kinase by glucocorticoid hormone is responsible for its special type of stimulative action on lipolysis."} {"id": "PMID:165366", "title": "Human plasma triglyceride labeling after high sucrose feeding. II. Study on triglyceride kinetics and postheparin lipolytic activity.", "content": "Kinetic studies of the very-low-density lipoprotein triglycerides (VLDL-TG) turnover by endogenous labeling with glycerol-2-3-H were performed in 13 patients in the postabsorptive state, first after 10-14 days on a low-sucrose high-starch diet, then again after 10-14 days of isocaloric high-sucrose low-starch diet (HSD). After HSD, a significant decrease in the fractional turnover rates of VLDL-TG was observed, as well as a modest but significant increase in its pool size, but the net turnover rates remained unchanged. Using Michaelis-Menten formulation, we have further calculated the Vmax and Km's of the removal system for VLDL-TG and found that the Vmax and Km's do not differ significantly between the two dietary periods. These results suggest that the removal mechanism for VLDL-TG has not changed after 10-14 days on the HSD, at least when the patients are studied in the postabsorptive state. Measurements of postheparin lipolytic acitivty under fed condition in 17 patients (including the 13 patients above) have shown a decrease after HSD. However, a defect in the removal of plasma-TG related to decreased activity of tissue-lipoprotein lipase in the fed state has not been conclusively uncovered by the kinetic studies performed in the postabsorptive state, and cannot contribute significantly to the expansion of VLDL-TG pool.", "contents": "Human plasma triglyceride labeling after high sucrose feeding. II. Study on triglyceride kinetics and postheparin lipolytic activity. Kinetic studies of the very-low-density lipoprotein triglycerides (VLDL-TG) turnover by endogenous labeling with glycerol-2-3-H were performed in 13 patients in the postabsorptive state, first after 10-14 days on a low-sucrose high-starch diet, then again after 10-14 days of isocaloric high-sucrose low-starch diet (HSD). After HSD, a significant decrease in the fractional turnover rates of VLDL-TG was observed, as well as a modest but significant increase in its pool size, but the net turnover rates remained unchanged. Using Michaelis-Menten formulation, we have further calculated the Vmax and Km's of the removal system for VLDL-TG and found that the Vmax and Km's do not differ significantly between the two dietary periods. These results suggest that the removal mechanism for VLDL-TG has not changed after 10-14 days on the HSD, at least when the patients are studied in the postabsorptive state. Measurements of postheparin lipolytic acitivty under fed condition in 17 patients (including the 13 patients above) have shown a decrease after HSD. However, a defect in the removal of plasma-TG related to decreased activity of tissue-lipoprotein lipase in the fed state has not been conclusively uncovered by the kinetic studies performed in the postabsorptive state, and cannot contribute significantly to the expansion of VLDL-TG pool."} {"id": "PMID:165367", "title": "Clinical testing of the hypothalamic-pituitary-adrenocortical system in states of hypo- and hypercortisolism.", "content": "Cortisol production is appropriately maintained by a complex control system which involves primarily the hypothalamus, the pituitary, and the adrenal cortices. Very small quantities of ACTH stimulate cortisol production, and maximum stimulation occurs with serum concentrations of only 3 mU/100 ML. Under normal circumstances, cortisol is secreted in bursts about ten times each day and circulates predominately bound to a specific binding protein which is rather completely saturated. Radioimmunoassay of plasma cortisol is now generally available and is the assay method of choice, but because of the episodic nature of its secretion, random values of plasma cortisol must be interpreted with great reservation, and even the comparison of morning and evening values in assessing circadian rhythmicity is not often helpful. Urinary free cortisol determinations provide excellent discrimination between normal function and all forms of hypercortisolism. Although the response of the adrenal cortices to ACTH may be evaluated in a number of different ways, the simplest but most definitive procedure involves continuous intravenous administration over a 48-hr period. Of the various tests which indirectly assess the potential for ACTH secretion, the use of metyrapone is most helpful. In the test of greatest utility, plasma cortisol and 11-desoxycortisol are determined the morning after a single midnight oral dose of 30 mg/kg. The detection of all forms of pathologic hypercortisolism is still best accomplished by the oral administration of dexamethasone. Plasma cortisol can be determined the morning after a single midnight dose of 1 mg, or urinary 17-hydroxycorticosteroids can be determined after 2 days in which 0.5 mg is given at 6-hr intervals. Patients with hypercortisolism of hypothalamic-pituitary origin usually evidence appropriate suppression of urinary steroids if the dose is increased to 2.0 mg every 6 hr for another 48 hr. In patients who do not suppress on this or even higher doses of dexamethasone, the distinction between those with adrenal tumor and those with the ectopic ACTH syndrome can be accomplished most definitively by the assay of plasma ACTH where this determination is available.", "contents": "Clinical testing of the hypothalamic-pituitary-adrenocortical system in states of hypo- and hypercortisolism. Cortisol production is appropriately maintained by a complex control system which involves primarily the hypothalamus, the pituitary, and the adrenal cortices. Very small quantities of ACTH stimulate cortisol production, and maximum stimulation occurs with serum concentrations of only 3 mU/100 ML. Under normal circumstances, cortisol is secreted in bursts about ten times each day and circulates predominately bound to a specific binding protein which is rather completely saturated. Radioimmunoassay of plasma cortisol is now generally available and is the assay method of choice, but because of the episodic nature of its secretion, random values of plasma cortisol must be interpreted with great reservation, and even the comparison of morning and evening values in assessing circadian rhythmicity is not often helpful. Urinary free cortisol determinations provide excellent discrimination between normal function and all forms of hypercortisolism. Although the response of the adrenal cortices to ACTH may be evaluated in a number of different ways, the simplest but most definitive procedure involves continuous intravenous administration over a 48-hr period. Of the various tests which indirectly assess the potential for ACTH secretion, the use of metyrapone is most helpful. In the test of greatest utility, plasma cortisol and 11-desoxycortisol are determined the morning after a single midnight oral dose of 30 mg/kg. The detection of all forms of pathologic hypercortisolism is still best accomplished by the oral administration of dexamethasone. Plasma cortisol can be determined the morning after a single midnight dose of 1 mg, or urinary 17-hydroxycorticosteroids can be determined after 2 days in which 0.5 mg is given at 6-hr intervals. Patients with hypercortisolism of hypothalamic-pituitary origin usually evidence appropriate suppression of urinary steroids if the dose is increased to 2.0 mg every 6 hr for another 48 hr. In patients who do not suppress on this or even higher doses of dexamethasone, the distinction between those with adrenal tumor and those with the ectopic ACTH syndrome can be accomplished most definitively by the assay of plasma ACTH where this determination is available."} {"id": "PMID:165391", "title": "Adenosine 3',5'-cyclic monophosphate in rabbit cerebrospinal fluid during fever induced by E. coli-endotoxin.", "content": "In rabbit cerebrospinal fluid during fever induced by E. coli-endotoxin adenosine 3',5'-cyclic monophosphate concentrations are about 2-fold higher in comparison to normal values. In addition to prostaglandins of the E series adenosine 3',5'-cyclic monophosphate might act as another mediator in the genesis of fever during infectious diseases.", "contents": "Adenosine 3',5'-cyclic monophosphate in rabbit cerebrospinal fluid during fever induced by E. coli-endotoxin. In rabbit cerebrospinal fluid during fever induced by E. coli-endotoxin adenosine 3',5'-cyclic monophosphate concentrations are about 2-fold higher in comparison to normal values. In addition to prostaglandins of the E series adenosine 3',5'-cyclic monophosphate might act as another mediator in the genesis of fever during infectious diseases."} {"id": "PMID:165392", "title": "Attempts to detect virus-specific DNA sequences in human tumors. III. Epstein-Barr viral DNA in non-lymphoid nasopharyngeal carcinoma cells.", "content": "Fourteen tumors of the nasopharyngeal region were analyzed for the presence of Epstein-Barr virus-specific DNA by DNA-cRNA hybridization. These data were compared to the histology of the respective tumors and the seroreactivity of the tumor-bearing patient against EBV-related antigens. With one exception, all tumor pieces containing nasopharyngeal carcinoma cells hybridized significantly with EBV-cRNA. Tumors of predominantly epithelial morphology annealed in the highest range. In situ-hybridization of freeze sections from a tumor containing almost equal amounts of tumor cells and lymphocytes revealed hybridizing DNA within nuclei of non-lymphoid cells. Although these data do not exclude the presence of EBV-DNA within lymphoid cells, they clearly demonstrate that in nasopharyngeal carcinomas the vast majority of EBV-specific DNA rests within non-lymphoid cells.", "contents": "Attempts to detect virus-specific DNA sequences in human tumors. III. Epstein-Barr viral DNA in non-lymphoid nasopharyngeal carcinoma cells. Fourteen tumors of the nasopharyngeal region were analyzed for the presence of Epstein-Barr virus-specific DNA by DNA-cRNA hybridization. These data were compared to the histology of the respective tumors and the seroreactivity of the tumor-bearing patient against EBV-related antigens. With one exception, all tumor pieces containing nasopharyngeal carcinoma cells hybridized significantly with EBV-cRNA. Tumors of predominantly epithelial morphology annealed in the highest range. In situ-hybridization of freeze sections from a tumor containing almost equal amounts of tumor cells and lymphocytes revealed hybridizing DNA within nuclei of non-lymphoid cells. Although these data do not exclude the presence of EBV-DNA within lymphoid cells, they clearly demonstrate that in nasopharyngeal carcinomas the vast majority of EBV-specific DNA rests within non-lymphoid cells."} {"id": "PMID:165393", "title": "In vitro cultivation of cells from the chorioallantoic membrane of chick embryos.", "content": "By treatment of chorioallantoic membranes from embryonated eggs with collagenase and hyaluronidase before the conventional application of trypsin cells could be grown in culture which supported growth of a large variety of myxoviruses, herpesviruses, avian reoviruses and the infectious bronchitis virus of chickens. The cultures could be used for sensitive plaque assays and neutralization tests.", "contents": "In vitro cultivation of cells from the chorioallantoic membrane of chick embryos. By treatment of chorioallantoic membranes from embryonated eggs with collagenase and hyaluronidase before the conventional application of trypsin cells could be grown in culture which supported growth of a large variety of myxoviruses, herpesviruses, avian reoviruses and the infectious bronchitis virus of chickens. The cultures could be used for sensitive plaque assays and neutralization tests."} {"id": "PMID:165397", "title": "Investigation of electron transport in the chloroplasts and their fragments by the ESR method. II. Light-induced interaction of water-soluble nitroxide radical with chloroplasts and chlorophyll containing protein-lipid micelles.", "content": "A light-induced reduction of the water-soluble nitroxide radical by chlorophyll in lipid and protein--lipid micelles was demonstrated. In contrast to model systems, in whole chloroplasts the NR is photoreduced by the electrons of the noncyclic electron transport chain. The initiation of cyclic electron transport in light particles, containing only photosystem I, does not lead to photoreduction of NR. When exogenous protein -- human serum albumin -- is added to the light particles, the nitroxide radicals are intensively reduced. The specific role of protein in electron transport from P700 to the exogenous acceptor is discussed.", "contents": "Investigation of electron transport in the chloroplasts and their fragments by the ESR method. II. Light-induced interaction of water-soluble nitroxide radical with chloroplasts and chlorophyll containing protein-lipid micelles. A light-induced reduction of the water-soluble nitroxide radical by chlorophyll in lipid and protein--lipid micelles was demonstrated. In contrast to model systems, in whole chloroplasts the NR is photoreduced by the electrons of the noncyclic electron transport chain. The initiation of cyclic electron transport in light particles, containing only photosystem I, does not lead to photoreduction of NR. When exogenous protein -- human serum albumin -- is added to the light particles, the nitroxide radicals are intensively reduced. The specific role of protein in electron transport from P700 to the exogenous acceptor is discussed."} {"id": "PMID:165398", "title": "Protein biosynthesis in a homologous, cell-free system in the presence of chick embryo RNA isolated from free and membrane-bound polyribosomes.", "content": "Protein synthesis has been studied in a cell-free system from chick embryo, in the presence of homologous RNA isolated from free and endoplasmic reticulum-bound polyribosomes. The two RNA fractions showed equal activities in total protein synthesis. However, while the RNA from bound polyribosomes mainly supported synthesis of high molecular weight, TCA-insoluble polypeptides, the RNA from free polyribosomes was more active in the synthesis of low molecular weight, TCA-soluble polypeptides. Optimal conditions for translation of the two RNA's under study were different when studied in a cell-free system with reduced content of endogenous matrix. Collagen synthesized in the system was identified by collagenase digestion. Collagen synthesis was demonstrated only in the presence of RNA from endoplasmic reticulum-bound polyribosomes, and represented 16-19% of total protein synthesis.", "contents": "Protein biosynthesis in a homologous, cell-free system in the presence of chick embryo RNA isolated from free and membrane-bound polyribosomes. Protein synthesis has been studied in a cell-free system from chick embryo, in the presence of homologous RNA isolated from free and endoplasmic reticulum-bound polyribosomes. The two RNA fractions showed equal activities in total protein synthesis. However, while the RNA from bound polyribosomes mainly supported synthesis of high molecular weight, TCA-insoluble polypeptides, the RNA from free polyribosomes was more active in the synthesis of low molecular weight, TCA-soluble polypeptides. Optimal conditions for translation of the two RNA's under study were different when studied in a cell-free system with reduced content of endogenous matrix. Collagen synthesized in the system was identified by collagenase digestion. Collagen synthesis was demonstrated only in the presence of RNA from endoplasmic reticulum-bound polyribosomes, and represented 16-19% of total protein synthesis."} {"id": "PMID:165401", "title": "Effects of DNA-polymerase-defective and recombination-deficient mutations on the ultraviolet sensitivity of Bacillus subtilis spores.", "content": "The DNA of UV-irradiated Bacillus subtilis spores, which contains 5-thyminyl-5,6-dihydrothymine (TDHT) as the major thymine photoproduct, is known to be repaired during germination by two complementary mechanisms: (I) the well-known excision repair, and (2) a special process, \"spore repair\", which destroys TDHT in situ without rendering it acid-soluble. In the absence of both mechanisms TDHT is not removed, and spores are highly UV-sensitive. When either of two mutations (pol-59 and pol-151) giving defective DNA polymerase, or one (rec-A1) giving a recombination deficiency are introduced into strains defective in one of these known TDHT removal processes, the chemically measured elimination of TDHT from spore DNA is unaltered, but spore UV-sensitivity is increased. The pol mutations produce their greatest sensitivity increase in spores of strains already deficient for the in situ destruction of TDHT, while the rec mutation gives its maximum sensitivity increase to spores of strains lacking excision. These facts argue that the pol mutations interfere mostly with excision repair (presumably its later resynthesis step), shile the rec mutation impairs \"spore repair\" in some step occurring subsequent to the TDHT destruction in situ. With either of these impairments of the later repair steps, DNA of UV-irradiated and germinated spores is considerably degraded, unless germination is carried out in the presence of chloramphenicol.", "contents": "Effects of DNA-polymerase-defective and recombination-deficient mutations on the ultraviolet sensitivity of Bacillus subtilis spores. The DNA of UV-irradiated Bacillus subtilis spores, which contains 5-thyminyl-5,6-dihydrothymine (TDHT) as the major thymine photoproduct, is known to be repaired during germination by two complementary mechanisms: (I) the well-known excision repair, and (2) a special process, \"spore repair\", which destroys TDHT in situ without rendering it acid-soluble. In the absence of both mechanisms TDHT is not removed, and spores are highly UV-sensitive. When either of two mutations (pol-59 and pol-151) giving defective DNA polymerase, or one (rec-A1) giving a recombination deficiency are introduced into strains defective in one of these known TDHT removal processes, the chemically measured elimination of TDHT from spore DNA is unaltered, but spore UV-sensitivity is increased. The pol mutations produce their greatest sensitivity increase in spores of strains already deficient for the in situ destruction of TDHT, while the rec mutation gives its maximum sensitivity increase to spores of strains lacking excision. These facts argue that the pol mutations interfere mostly with excision repair (presumably its later resynthesis step), shile the rec mutation impairs \"spore repair\" in some step occurring subsequent to the TDHT destruction in situ. With either of these impairments of the later repair steps, DNA of UV-irradiated and germinated spores is considerably degraded, unless germination is carried out in the presence of chloramphenicol."} {"id": "PMID:165402", "title": "Genetic analysis of radiation sensitive and chemical-mutagen sensitive mutants of Pseudomonas aeruginosa.", "content": "Thirty-five mutants of Pseudomonas aeruginosa sensitive to methyl methanesulfonate (MMS) have been genetically characterized. They constitute ten separable groups as defined by transduction and conjugation. Three of the groups have been shown to be cotransducible with auxotrophic markers.", "contents": "Genetic analysis of radiation sensitive and chemical-mutagen sensitive mutants of Pseudomonas aeruginosa. Thirty-five mutants of Pseudomonas aeruginosa sensitive to methyl methanesulfonate (MMS) have been genetically characterized. They constitute ten separable groups as defined by transduction and conjugation. Three of the groups have been shown to be cotransducible with auxotrophic markers."} {"id": "PMID:165404", "title": "Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids.", "content": "Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia.", "contents": "Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia."} {"id": "PMID:165407", "title": "Etiology of nongonococcal urethritis.", "content": "Chlamydia trachomatis was isolated from the urethra from 48 (42 per cent) of 113 men with non-gonococcal urethritis (NGU), four (7 per cent) of 58 without overt urethritis, and 13 (19 per cent) of 69 with gonorrhea. Postgonococcal urethritis (PGU) developed in 11 of 11 men who had C. trum antibody to C. trachomatisis developed. The immunotype specificity of chlamydial antibody corresponded to the immunotype isolated. Among culture-negative patients. chlamydial antibody prevalence correlated with the number of past sex partners and with previous NGU. Herpesvirus hominis, cytomegalovirus, T-mycoplasma, Mycoplasma hominis, other bacteria, and Trichomonas vaginalis were not implicated in NGU or PGU. Thus, the cause of chlamydia-negative NGU and PGU remains obscure. Endocervical chlamydia were found in sex partners of 15 of 22 NGU patients with and two of 24 without urethral chlamydial infection (p smaller than 0.001). Tetracycline treatment of both sex partners appears advisable.", "contents": "Etiology of nongonococcal urethritis. Chlamydia trachomatis was isolated from the urethra from 48 (42 per cent) of 113 men with non-gonococcal urethritis (NGU), four (7 per cent) of 58 without overt urethritis, and 13 (19 per cent) of 69 with gonorrhea. Postgonococcal urethritis (PGU) developed in 11 of 11 men who had C. trum antibody to C. trachomatisis developed. The immunotype specificity of chlamydial antibody corresponded to the immunotype isolated. Among culture-negative patients. chlamydial antibody prevalence correlated with the number of past sex partners and with previous NGU. Herpesvirus hominis, cytomegalovirus, T-mycoplasma, Mycoplasma hominis, other bacteria, and Trichomonas vaginalis were not implicated in NGU or PGU. Thus, the cause of chlamydia-negative NGU and PGU remains obscure. Endocervical chlamydia were found in sex partners of 15 of 22 NGU patients with and two of 24 without urethral chlamydial infection (p smaller than 0.001). Tetracycline treatment of both sex partners appears advisable."} {"id": "PMID:165416", "title": "Acquired agammaglobulinemia after a life-threatening illness with clinical and laboratory features of infectious mononucleosis in three related male children.", "content": "Three males in one family (two siblings and one maternal cousin) had an illness with cervical adenopathy, hepatosplenomegaly, and a fulminant febrile course. In the two survivors agammaglobulinemia developed. One of them became ill at the age of six months and had an Epstein-Barr-virus antibody titer of 1:10 during illness and convalescence. The white-cell count was 120,000 with 90 per cent lymphocytes, most being atypical and forming increased numbers of sheep erythrocyte rosettes. IgM was elevated, IgA normal and IgG decreased. Subsequently, all immunoglobulins were absent, and the Epstein-Barr-virus antibody titer became negative. Peripheral B-cell number remained normal, but abnormal lymph-node architecture associated with failure to respond to antigenic challenge indicated B-cell dysfunction. The pathogenesis of this entity may involve an abnormal T-cell response to transformation of B cells by Epstein-Barr virus, leading to B-cell dysfunction and agammaglobulinemia.", "contents": "Acquired agammaglobulinemia after a life-threatening illness with clinical and laboratory features of infectious mononucleosis in three related male children. Three males in one family (two siblings and one maternal cousin) had an illness with cervical adenopathy, hepatosplenomegaly, and a fulminant febrile course. In the two survivors agammaglobulinemia developed. One of them became ill at the age of six months and had an Epstein-Barr-virus antibody titer of 1:10 during illness and convalescence. The white-cell count was 120,000 with 90 per cent lymphocytes, most being atypical and forming increased numbers of sheep erythrocyte rosettes. IgM was elevated, IgA normal and IgG decreased. Subsequently, all immunoglobulins were absent, and the Epstein-Barr-virus antibody titer became negative. Peripheral B-cell number remained normal, but abnormal lymph-node architecture associated with failure to respond to antigenic challenge indicated B-cell dysfunction. The pathogenesis of this entity may involve an abnormal T-cell response to transformation of B cells by Epstein-Barr virus, leading to B-cell dysfunction and agammaglobulinemia."} {"id": "PMID:165418", "title": "Evidence for normal thyroidal adenyl cyclase, cyclic AMP-binding and protein-kinase activities in Graves' disease.", "content": "The adenyl cyclase, cAMP-binding and protein-kinase activities have been studied in thyroid glands from patients with Graves' disease in comparison with normal thyroid glands. The basal and TSH-stimulated adenyl cyclase activities were tested in crude plasma membrane preparations. The characteristics of the intracellular binding of cAMP, i.e., the maximal binding capacity (MBC) for cAMP and affinity constant (Ka) of the binding, and the basal and cAMP-stimulated protein-kinase activities, were estimated in both the soluble and particulate fractions of thyroid tissue. All of these parameters studied were essentially normal in Graves' disease. It is concluded that hyperthyroidism in Graves' disease is probably not a result of qualitative or quantitative abnormalities in the adenyl cyclase-cAMP protein-kinase system.", "contents": "Evidence for normal thyroidal adenyl cyclase, cyclic AMP-binding and protein-kinase activities in Graves' disease. The adenyl cyclase, cAMP-binding and protein-kinase activities have been studied in thyroid glands from patients with Graves' disease in comparison with normal thyroid glands. The basal and TSH-stimulated adenyl cyclase activities were tested in crude plasma membrane preparations. The characteristics of the intracellular binding of cAMP, i.e., the maximal binding capacity (MBC) for cAMP and affinity constant (Ka) of the binding, and the basal and cAMP-stimulated protein-kinase activities, were estimated in both the soluble and particulate fractions of thyroid tissue. All of these parameters studied were essentially normal in Graves' disease. It is concluded that hyperthyroidism in Graves' disease is probably not a result of qualitative or quantitative abnormalities in the adenyl cyclase-cAMP protein-kinase system."} {"id": "PMID:165419", "title": "A sensitive bioassay for the determination of human plasma ACTH levels.", "content": "A sensitive bioassay for the measurement of plasma ACTH is presented. The use of silicic acid adsorption of plasma, with a subsequent acid wash and aqueous acetone desorption, was successful in removing those substances which had interfered with the steroidogenic response of dispersed adrenal cells when unextracted plasma was employed. This extraction procedure extracted 72-76% of ACTH present in plasma. Two pg ACTH1-39 could be consistently detected. Alpha-hACTH1-39 and alpha-pACTH1-39 exhibited equal potencies. Beta-MSH was ineffective at dosage levels up to 2 x 10(8) pg. One x 10(8) pg of ACTH1-10, ACTH4-10, or alpha-MSH had a steroidogenic effect equivalent to that of 40 pg ACTH1-39. ACTH 17-39 and ACTH 11-24 were incapable of stimulating steroid production at doses of 1 x 10(8) pg. Excesses of the latter, but not of the former appeared to be able to antagonize the steroidogenic effect of ACTH1-39. Plasma from normal subjects, bioassayed by this extraction procedure, contained 12-186 pg/ml ACTH at 0400-0800: 14-93 pg/ml ACTH at 1000-1300, and less than 10-34 pg/ml ACTH at 1600-2200. Hypoglycemia and vasopressin administration were followed by increases in plasma ACTH concentratrations. Plasma ACTH concentrations in untreated patients with Cushing's disease (sampled over the period 0900-1300) ranged from 65-220 pg/ml. Three patients with Addison's disease (untreated or 12 h following replacement steroid withdrawal) had ACTH concentrations of 223, 370 and 1226 pg/ml. Markedly elevated ACTH concentrations were observed in a patient with Nelson's syndrome (391 and 835 pg/ml). Bioassayable ACTH was not detected in 2 patients with panhypopituitarism.", "contents": "A sensitive bioassay for the determination of human plasma ACTH levels. A sensitive bioassay for the measurement of plasma ACTH is presented. The use of silicic acid adsorption of plasma, with a subsequent acid wash and aqueous acetone desorption, was successful in removing those substances which had interfered with the steroidogenic response of dispersed adrenal cells when unextracted plasma was employed. This extraction procedure extracted 72-76% of ACTH present in plasma. Two pg ACTH1-39 could be consistently detected. Alpha-hACTH1-39 and alpha-pACTH1-39 exhibited equal potencies. Beta-MSH was ineffective at dosage levels up to 2 x 10(8) pg. One x 10(8) pg of ACTH1-10, ACTH4-10, or alpha-MSH had a steroidogenic effect equivalent to that of 40 pg ACTH1-39. ACTH 17-39 and ACTH 11-24 were incapable of stimulating steroid production at doses of 1 x 10(8) pg. Excesses of the latter, but not of the former appeared to be able to antagonize the steroidogenic effect of ACTH1-39. Plasma from normal subjects, bioassayed by this extraction procedure, contained 12-186 pg/ml ACTH at 0400-0800: 14-93 pg/ml ACTH at 1000-1300, and less than 10-34 pg/ml ACTH at 1600-2200. Hypoglycemia and vasopressin administration were followed by increases in plasma ACTH concentratrations. Plasma ACTH concentrations in untreated patients with Cushing's disease (sampled over the period 0900-1300) ranged from 65-220 pg/ml. Three patients with Addison's disease (untreated or 12 h following replacement steroid withdrawal) had ACTH concentrations of 223, 370 and 1226 pg/ml. Markedly elevated ACTH concentrations were observed in a patient with Nelson's syndrome (391 and 835 pg/ml). Bioassayable ACTH was not detected in 2 patients with panhypopituitarism."} {"id": "PMID:165427", "title": "5'-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation.", "content": "Unmethylated reovirus and VSV mRNAs are specifically methylated to form 5'-terminal structures of the type, m-7-G(5')ppp(5')N by protein synthesising extracts prepared from wheat germ and mouse L cells. Reticulocyte mRNA also contains 5'-terminal m-7-G. MRNAs having 5'-terminal m-7-G stimulate protein synthesis in vitro. Removal of m-7-G by beta-elimination abolishes translation of the mRNAs.", "contents": "5'-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Unmethylated reovirus and VSV mRNAs are specifically methylated to form 5'-terminal structures of the type, m-7-G(5')ppp(5')N by protein synthesising extracts prepared from wheat germ and mouse L cells. Reticulocyte mRNA also contains 5'-terminal m-7-G. MRNAs having 5'-terminal m-7-G stimulate protein synthesis in vitro. Removal of m-7-G by beta-elimination abolishes translation of the mRNAs."} {"id": "PMID:165431", "title": "Induction of increased calcium uptake in mouse T lymphocytes by concanavalin A and its modulation by cyclic nucleotides.", "content": "The binding of concanavqlin A to T but not B mouse spleen lymphocytes increases Ca-2+ uptake in these cells which is measurable by 45 s and complete by 1 min. Dibutyrl cyclic AMP, but not sodium azide inhibits induced Ca-2+ uptake, wheras dibutyryl cyclic GMP enhances it. B cell mitogens do not cause a similar Ca-2+ uptake in mouse B lymphocytes. The induction of increased Ca-2+ uptake by T cells is discussed in terms of gated membrane channels for Ca-2+.", "contents": "Induction of increased calcium uptake in mouse T lymphocytes by concanavalin A and its modulation by cyclic nucleotides. The binding of concanavqlin A to T but not B mouse spleen lymphocytes increases Ca-2+ uptake in these cells which is measurable by 45 s and complete by 1 min. Dibutyrl cyclic AMP, but not sodium azide inhibits induced Ca-2+ uptake, wheras dibutyryl cyclic GMP enhances it. B cell mitogens do not cause a similar Ca-2+ uptake in mouse B lymphocytes. The induction of increased Ca-2+ uptake by T cells is discussed in terms of gated membrane channels for Ca-2+."} {"id": "PMID:165438", "title": "Role of the renin-angiotensin-aldosterone system in the regulation of plasma potassium in chronic renal disease.", "content": "The relationship between plasma potassium concentration and the renin-angiotensin-aldosterone system was evaluated in ten patients with chronic renal failure (creatinine clearance 10-56 ml/min). Under basal conditions and following various stimulation maneuvers, normokalemic patients demonstrated normal plasma renin and aldosterone levels. Five of six patients with hyperkalemia had diminished function of the renin-angiotensin-aldosterone system; their ability to conserve sodium during salt depletion was less than that of normokalemic patients. The data suggest that the maintenance of plasma potassium levels in these patients is dependent of the presence of a normally functioning renin-angiotensin-aldosterone system; aldosterone activity may be an important determinant of sodium conservation in patients with renal failure.", "contents": "Role of the renin-angiotensin-aldosterone system in the regulation of plasma potassium in chronic renal disease. The relationship between plasma potassium concentration and the renin-angiotensin-aldosterone system was evaluated in ten patients with chronic renal failure (creatinine clearance 10-56 ml/min). Under basal conditions and following various stimulation maneuvers, normokalemic patients demonstrated normal plasma renin and aldosterone levels. Five of six patients with hyperkalemia had diminished function of the renin-angiotensin-aldosterone system; their ability to conserve sodium during salt depletion was less than that of normokalemic patients. The data suggest that the maintenance of plasma potassium levels in these patients is dependent of the presence of a normally functioning renin-angiotensin-aldosterone system; aldosterone activity may be an important determinant of sodium conservation in patients with renal failure."} {"id": "PMID:165440", "title": "Mononeuropathy multiplex as a complication of amphetamine angiitis.", "content": "A patient who abused multiple drugs developed a rapidly progressive mononeuropathy multiplex, which appeared to respond to corticosteroid therapy with partial resolution. Intravenous methamphetamine had been used almost exclusively from the fourth month prior to the onset of symptoms. Biopsy material revealed a necrotizing angiitis involving medium and small sized arteries, capillaries, and venules, typical of a hypersensitivity-type angiopathy, rather than the previously reported polyarteritis nodosa-type lesions secondary to illicit drugs. The apparent response to corticosteroids suggests that these agents might be useful in the treatment of some complications of drug abuse.", "contents": "Mononeuropathy multiplex as a complication of amphetamine angiitis. A patient who abused multiple drugs developed a rapidly progressive mononeuropathy multiplex, which appeared to respond to corticosteroid therapy with partial resolution. Intravenous methamphetamine had been used almost exclusively from the fourth month prior to the onset of symptoms. Biopsy material revealed a necrotizing angiitis involving medium and small sized arteries, capillaries, and venules, typical of a hypersensitivity-type angiopathy, rather than the previously reported polyarteritis nodosa-type lesions secondary to illicit drugs. The apparent response to corticosteroids suggests that these agents might be useful in the treatment of some complications of drug abuse."} {"id": "PMID:165446", "title": "A cytochemical study of some enzyme activities in biliverdin-treated cell cultures.", "content": "The authors studied the modifications of the activities of some enzymes in cell cultures submitted to the action of biliverdin. This biliary pigment rapidly induces a remarkable increase in alkaline phosphatase and ATP-ase activities and subsequently, an activation of acid phosphatase and beta-glucuronidase. On the contrary, 5'-nucleotidase and glucose-6-phosphatase activities remain unchanged. These results are discussed and compared with those obtained in our and other laboratories by using unconjugated bilirubin on different biological substrates.", "contents": "A cytochemical study of some enzyme activities in biliverdin-treated cell cultures. The authors studied the modifications of the activities of some enzymes in cell cultures submitted to the action of biliverdin. This biliary pigment rapidly induces a remarkable increase in alkaline phosphatase and ATP-ase activities and subsequently, an activation of acid phosphatase and beta-glucuronidase. On the contrary, 5'-nucleotidase and glucose-6-phosphatase activities remain unchanged. These results are discussed and compared with those obtained in our and other laboratories by using unconjugated bilirubin on different biological substrates."} {"id": "PMID:165447", "title": "[Immunochemical study of liver metastases of colonic tumors].", "content": "This work demonstrated that anti-CEA and anti-NCA antibodies can be obtained from liver metastases of colonic carcinoma. The various antigens that have been identifiedin colonic tumor are found in liver metastases. Furthermore, the healthy parts of a metastatic liver contain not only CEA but also NCA.", "contents": "[Immunochemical study of liver metastases of colonic tumors]. This work demonstrated that anti-CEA and anti-NCA antibodies can be obtained from liver metastases of colonic carcinoma. The various antigens that have been identifiedin colonic tumor are found in liver metastases. Furthermore, the healthy parts of a metastatic liver contain not only CEA but also NCA."} {"id": "PMID:165448", "title": "[Viral contamination in laboratories and hospital units].", "content": "Viral contamination is at least as important in hospital laboratories and wards as contamination by bacteria or microscopic fungi, but it is much more insidious and sometimes unrecognized. There are two main types: The first has a purely technical effect and only interest the virologist. This is contamination of reagents, reference strains, cell cultures, etc.., by foreign viral agents. It may be the cause of errors on diagnosis or regrettable errors of interpretation of certain experimental data. It is most difficult to detect, if not to avoid. The second is much more worrying as it is liable to cause disease in man, which may induce severe, and even fatal infections in patients or in the medical, para-medical and technical personnel. This is the case with type B hepatitis virus which tends to invade surgical units using extra-corporeal circulation, hemodialysis units and transplantation units, blood transfusion centres, dental units and even causes victims in routine laboratories. However, type B hepatitis is not the only virus which may lead to severe infections; other viruses include: poxvirus, cytomegalovirus, arbovirus, etc. Finally, other often severe accidents may occur in research laboratories and in the pharmaceutical industry, owing to manipulation of dangerous viruses or by contact with experimental animals, e.g. rodents, or monkeys, which contain the virus in a latent state, e.g. lymphocytic choriomeningitis, Sabin virus, Marburg virus, type A hepatitis virus, etc. With regard to such accidents, we are almost completely powerless from the therapeutic point of view and, even poorly equipped, from the point of view of prophylaxis.", "contents": "[Viral contamination in laboratories and hospital units]. Viral contamination is at least as important in hospital laboratories and wards as contamination by bacteria or microscopic fungi, but it is much more insidious and sometimes unrecognized. There are two main types: The first has a purely technical effect and only interest the virologist. This is contamination of reagents, reference strains, cell cultures, etc.., by foreign viral agents. It may be the cause of errors on diagnosis or regrettable errors of interpretation of certain experimental data. It is most difficult to detect, if not to avoid. The second is much more worrying as it is liable to cause disease in man, which may induce severe, and even fatal infections in patients or in the medical, para-medical and technical personnel. This is the case with type B hepatitis virus which tends to invade surgical units using extra-corporeal circulation, hemodialysis units and transplantation units, blood transfusion centres, dental units and even causes victims in routine laboratories. However, type B hepatitis is not the only virus which may lead to severe infections; other viruses include: poxvirus, cytomegalovirus, arbovirus, etc. Finally, other often severe accidents may occur in research laboratories and in the pharmaceutical industry, owing to manipulation of dangerous viruses or by contact with experimental animals, e.g. rodents, or monkeys, which contain the virus in a latent state, e.g. lymphocytic choriomeningitis, Sabin virus, Marburg virus, type A hepatitis virus, etc. With regard to such accidents, we are almost completely powerless from the therapeutic point of view and, even poorly equipped, from the point of view of prophylaxis."} {"id": "PMID:165449", "title": "[Prolactin and breast cancers].", "content": "Prolactin has a cocarcinogenic activity in the rat and mouse as its administration or stimulation of endogenous secretion increases the incidence and reduces the latent period of breast tumours, whether spontaneous or induced by chemical carcinogens. Prolonged hyperprolactinemia obtained by neutralizing the inhibitory influence of the hypothalamus on its secretion and liberation, favours the development of breast carcinoma and inversely. (Estrogens and prolactin exert a synergistic effect, both centrally and peripherally, on the acinar cells of the breast. Prolactin dependency of these mammary carcinomas is due to the persistence of specific cell receptors. In human pathology, it has not yet been possible to demonstrate a comparable effect of prolactin. Radioimmunoassay of plasma prolactin and specific receptors, together with epidemiological enquiries, should rapidly confirm or refute the cocarcinogenic effect of prolactin.", "contents": "[Prolactin and breast cancers]. Prolactin has a cocarcinogenic activity in the rat and mouse as its administration or stimulation of endogenous secretion increases the incidence and reduces the latent period of breast tumours, whether spontaneous or induced by chemical carcinogens. Prolonged hyperprolactinemia obtained by neutralizing the inhibitory influence of the hypothalamus on its secretion and liberation, favours the development of breast carcinoma and inversely. (Estrogens and prolactin exert a synergistic effect, both centrally and peripherally, on the acinar cells of the breast. Prolactin dependency of these mammary carcinomas is due to the persistence of specific cell receptors. In human pathology, it has not yet been possible to demonstrate a comparable effect of prolactin. Radioimmunoassay of plasma prolactin and specific receptors, together with epidemiological enquiries, should rapidly confirm or refute the cocarcinogenic effect of prolactin."} {"id": "PMID:165450", "title": "Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function.", "content": "To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71% of predicted value in group 1, 58% in group 2, and 94% in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated.", "contents": "Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function. To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71% of predicted value in group 1, 58% in group 2, and 94% in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated."} {"id": "PMID:165452", "title": "Sudden infant death syndrome: hypothesis of causation.", "content": "The airway of the young infant is anatomically vulnerable at the oropharyngeal level between the soft palate and the base of the skull. Airway occlusion at this level might occur during the muscle relaxation which occurs during REM sleep, facilitated by a hypermobile mandible, by the hypotonia of infection, perhaps by an enlarged tongue with a strong backwards sucking action which might be the result of the artificial feeding of the infant. It is possible that \"cot deaths\" (SIDS) may be precipitated by such oropharyngeal airway occlusion, cardiac arrest following variable periods of partial or complete oxygen deprivation.", "contents": "Sudden infant death syndrome: hypothesis of causation. The airway of the young infant is anatomically vulnerable at the oropharyngeal level between the soft palate and the base of the skull. Airway occlusion at this level might occur during the muscle relaxation which occurs during REM sleep, facilitated by a hypermobile mandible, by the hypotonia of infection, perhaps by an enlarged tongue with a strong backwards sucking action which might be the result of the artificial feeding of the infant. It is possible that \"cot deaths\" (SIDS) may be precipitated by such oropharyngeal airway occlusion, cardiac arrest following variable periods of partial or complete oxygen deprivation."} {"id": "PMID:165453", "title": "Antiviral chemotherapy and neonatal herpes simplex virus infecition: a pilot study--experience with adenine arabinoside (ARA-A).", "content": "Among 13 neonates with herpes simplex virus (HSV) infection, eight had disseminated disease, one localized CNS disease, and in four the infection was confined to the skin and eyes. Ara-A, a purine nucleoside with anti-viral activity against DNA-VIRUSES, WAS GIVEN (10 TO 20 MG/MG/DAY) BY A CONTINUOUS 12-HOUR INTRAVENOUS DRIP FOR 10 TO 15 DAYS. In all, ara-A administration was begun within three to eight days after the appearance of skin vesicles which represented the hallmark of the disease. Both diagnosis and ara-A treatment were much delayed in one infant without skin vesicles and four infants whose skin vesicles appeared late, long after the occurrence of CNS damage. In this group of infants with disseminated disease, four died and one infant was left with severe neurological deficits. Eight infants (four with disseminated and four with localized skin disease) with skin vesicles as the earliest sign of infection received ara-A early, within three days after the onset of neurologic signs. All survived with no neurologic deficit at 6 months to 1 year of age. There was no apparent toxicity of ara-A to the bonemarrow, liver, or kidney.", "contents": "Antiviral chemotherapy and neonatal herpes simplex virus infecition: a pilot study--experience with adenine arabinoside (ARA-A). Among 13 neonates with herpes simplex virus (HSV) infection, eight had disseminated disease, one localized CNS disease, and in four the infection was confined to the skin and eyes. Ara-A, a purine nucleoside with anti-viral activity against DNA-VIRUSES, WAS GIVEN (10 TO 20 MG/MG/DAY) BY A CONTINUOUS 12-HOUR INTRAVENOUS DRIP FOR 10 TO 15 DAYS. In all, ara-A administration was begun within three to eight days after the appearance of skin vesicles which represented the hallmark of the disease. Both diagnosis and ara-A treatment were much delayed in one infant without skin vesicles and four infants whose skin vesicles appeared late, long after the occurrence of CNS damage. In this group of infants with disseminated disease, four died and one infant was left with severe neurological deficits. Eight infants (four with disseminated and four with localized skin disease) with skin vesicles as the earliest sign of infection received ara-A early, within three days after the onset of neurologic signs. All survived with no neurologic deficit at 6 months to 1 year of age. There was no apparent toxicity of ara-A to the bonemarrow, liver, or kidney."} {"id": "PMID:165454", "title": "The absorption of iron as supplements in infant cereal and infant formulas.", "content": "The absorption of iron was measured from isotopically tagged salts used in supplementing infant cereals and as the iron supplement in cow's milk and soy-based formulas. Iron as sodium iron pryophosphate and ferric orthophosphate were poorly absorbed from infant cereal (mean, smaller than 1.0%) and thus are not dependable sources of iron to meet the nutritional needs of infants. Reduced iron of very small particle size and ferrous sulfate when added to cereal was absorbed to a greater extent (mean, 4.0% and 2.7% respectively). For technical reasons, these two forms of iron had not been added to commercial cereal products because of discoloration, distribution problems of the iron in the product, and shortened shelf life. Therefore, at the present time, iron supplementation of infant cereals with sodium iron pyrophosphate, ferric orthophosphate, and reduced iron of large particle size does not provide a predictable and available source of iron to meet the needs of infants. Supplemental iron as ferrous sulfate in milk- and soy-based formulas gave a mean absorption of 3.4% and 5.4%. The iron supplements in these formulas can essentially meet the needs for dietary iron of healthy infants.", "contents": "The absorption of iron as supplements in infant cereal and infant formulas. The absorption of iron was measured from isotopically tagged salts used in supplementing infant cereals and as the iron supplement in cow's milk and soy-based formulas. Iron as sodium iron pryophosphate and ferric orthophosphate were poorly absorbed from infant cereal (mean, smaller than 1.0%) and thus are not dependable sources of iron to meet the nutritional needs of infants. Reduced iron of very small particle size and ferrous sulfate when added to cereal was absorbed to a greater extent (mean, 4.0% and 2.7% respectively). For technical reasons, these two forms of iron had not been added to commercial cereal products because of discoloration, distribution problems of the iron in the product, and shortened shelf life. Therefore, at the present time, iron supplementation of infant cereals with sodium iron pyrophosphate, ferric orthophosphate, and reduced iron of large particle size does not provide a predictable and available source of iron to meet the needs of infants. Supplemental iron as ferrous sulfate in milk- and soy-based formulas gave a mean absorption of 3.4% and 5.4%. The iron supplements in these formulas can essentially meet the needs for dietary iron of healthy infants."} {"id": "PMID:165461", "title": "[Chemotherapeutic combinations of mutually potentiating drugs. 3-Application to primary tumors of the central nervous system].", "content": "17 patients suffering from primary tumours of the central nervous system recurring after surgery and/or radiotherapy, received chemotherapy consisting of the administration of VM 26 followed by CCNU. Each cycle of treatment lasted four days and was restarted only after an average interval of 30 days to allow for haematological recovery. All of the patients in the trial have been under treatment for eight months. Five (28 p.cent) are at present in complete remission with no residual clinical, isotopic or radiological signs. In six others there was tumour regression and in four neurological stabilisation. In all those cases where objective tumour regression was obtained functional improvement was noted.", "contents": "[Chemotherapeutic combinations of mutually potentiating drugs. 3-Application to primary tumors of the central nervous system]. 17 patients suffering from primary tumours of the central nervous system recurring after surgery and/or radiotherapy, received chemotherapy consisting of the administration of VM 26 followed by CCNU. Each cycle of treatment lasted four days and was restarted only after an average interval of 30 days to allow for haematological recovery. All of the patients in the trial have been under treatment for eight months. Five (28 p.cent) are at present in complete remission with no residual clinical, isotopic or radiological signs. In six others there was tumour regression and in four neurological stabilisation. In all those cases where objective tumour regression was obtained functional improvement was noted."} {"id": "PMID:165462", "title": "[Peculiarities of lymphocytes during dermatosis. Ultrastructural study of 100 cases].", "content": "Peripheral blood lymphocytes from one hundred patients with skin disorders have been examined under the electron microscope. The bloods of 20 donors were used as controls. One observed: Branched Tubular Structures (so-called Lupus type inclusions) in 8 cases (4 systemic Lupus Erythematosus out of 15; I mixed connective tissue disorder; 3 cutaneous lymphomas). As regards Lupus, these findings are in agreement with those already reported in the literature. However, the presence of such inclusions in Lymphomas calls attention once again on the fact that the lymphocyte appears like a possible common denominator to both autoimmune diseases and lymphomas; Intented or cerebriform nuclei in 12 cases, all lymphomas, including 8 cases of Sezary Syndrome out of 8 and 4 Mycosis Fungo\u00efdes out of 12; Lamellar type inclusions, similar to those described by Hovig, in 13 cases (connective tissue disease 1, lymphomas 2, psoriasis 4, miscellaneous 4, healthy controls 2). Their meaning is unclear; they may be artifacts.", "contents": "[Peculiarities of lymphocytes during dermatosis. Ultrastructural study of 100 cases]. Peripheral blood lymphocytes from one hundred patients with skin disorders have been examined under the electron microscope. The bloods of 20 donors were used as controls. One observed: Branched Tubular Structures (so-called Lupus type inclusions) in 8 cases (4 systemic Lupus Erythematosus out of 15; I mixed connective tissue disorder; 3 cutaneous lymphomas). As regards Lupus, these findings are in agreement with those already reported in the literature. However, the presence of such inclusions in Lymphomas calls attention once again on the fact that the lymphocyte appears like a possible common denominator to both autoimmune diseases and lymphomas; Intented or cerebriform nuclei in 12 cases, all lymphomas, including 8 cases of Sezary Syndrome out of 8 and 4 Mycosis Fungo\u00efdes out of 12; Lamellar type inclusions, similar to those described by Hovig, in 13 cases (connective tissue disease 1, lymphomas 2, psoriasis 4, miscellaneous 4, healthy controls 2). Their meaning is unclear; they may be artifacts."} {"id": "PMID:165465", "title": "[Is progesterone insufficiency carcihogenic?].", "content": "Estradiol is a natural estrogen which favors cellular hyperplasia at the level of its target organs. As for progesterone, its activity may be synergic or antagonist of estradiol. In the first case, progesterone has generally a secretory activity upon the target cells \"prepared\" by estrogens, in particular the cells of the female genital tract (uterus, breast). In the second case, progesterone may be an antiestrogen not only at the level of genital cells but also at the level of other receptors such as vascular system, etc. If an unbalance occurs in the quantitative and chronological ratio between estradiol and progesterone production (which determines the number of target cells and their secretory activity), a cellular dysplasia may be observed. This unbalance is generally characterized by an insufficiency in progesterone secretion which may be physiological (puberty, menopause) or pathological. Such a progesterone insufficiency may play a role in the pathogenesis of genital cancers (endometrial and possibly mammary). Experimental data which give some support to such an hypothesis are reported. They emphasize the importance of treatment of the progesterone insufficiency of the premenopausal period in women with the aim of preventing cellular dysplasia of the female genital tract.", "contents": "[Is progesterone insufficiency carcihogenic?]. Estradiol is a natural estrogen which favors cellular hyperplasia at the level of its target organs. As for progesterone, its activity may be synergic or antagonist of estradiol. In the first case, progesterone has generally a secretory activity upon the target cells \"prepared\" by estrogens, in particular the cells of the female genital tract (uterus, breast). In the second case, progesterone may be an antiestrogen not only at the level of genital cells but also at the level of other receptors such as vascular system, etc. If an unbalance occurs in the quantitative and chronological ratio between estradiol and progesterone production (which determines the number of target cells and their secretory activity), a cellular dysplasia may be observed. This unbalance is generally characterized by an insufficiency in progesterone secretion which may be physiological (puberty, menopause) or pathological. Such a progesterone insufficiency may play a role in the pathogenesis of genital cancers (endometrial and possibly mammary). Experimental data which give some support to such an hypothesis are reported. They emphasize the importance of treatment of the progesterone insufficiency of the premenopausal period in women with the aim of preventing cellular dysplasia of the female genital tract."} {"id": "PMID:165466", "title": "[Relation between endocrinology and psychiatry. Some recent developments].", "content": "Relations between Endocrinology and Psychiatry are developing in two main directions: Behavioural effects of hormones. After the effects of peripheral hormones, recent works are concerned with A.C.T.H. and Antidiuretic Hormone (which interfere with memory process) and with Hypothalamic Peptides (which might have psychotropic properties, independant of their endocrine regulation function). -Correlations between psychiatric syndroms and endocrine disorders. In some mentally depressed patients, disorders of the hypothalamic control of Coricotrophin, Growth Hormone and Thyreo-stimulating Hormone, have been observed. As many psychotropic drugs can influence the secretion of Prolactin, a systematic survey of this hormone in various mental illnesses, is suggested.", "contents": "[Relation between endocrinology and psychiatry. Some recent developments]. Relations between Endocrinology and Psychiatry are developing in two main directions: Behavioural effects of hormones. After the effects of peripheral hormones, recent works are concerned with A.C.T.H. and Antidiuretic Hormone (which interfere with memory process) and with Hypothalamic Peptides (which might have psychotropic properties, independant of their endocrine regulation function). -Correlations between psychiatric syndroms and endocrine disorders. In some mentally depressed patients, disorders of the hypothalamic control of Coricotrophin, Growth Hormone and Thyreo-stimulating Hormone, have been observed. As many psychotropic drugs can influence the secretion of Prolactin, a systematic survey of this hormone in various mental illnesses, is suggested."} {"id": "PMID:165468", "title": "Determination of the 3' terminal nucleotide of DNA fragments.", "content": "A new method for determining the 3'-terminal nucleotide of a DNA strand is presented. Use is made of the fact that one (and only one) 2',3'-dideoxyribonucleotide can be added to the 3'-end of a DNA fragment with calf thymus terminal transferase. Addition of more than one nucleotide analog per strand is impossible due to the absence of a 3'-terminal hydroxyl group. If the terminatind dideoxyribonucleotide contains an (alpha 32p) label, the resulting 3'-blocked strand can be digested by \"nearest neighbor\" techniques and the original 3'-endgroup determined. Picomole quantities of DNA strands can be labeled and the 3'-end determined.", "contents": "Determination of the 3' terminal nucleotide of DNA fragments. A new method for determining the 3'-terminal nucleotide of a DNA strand is presented. Use is made of the fact that one (and only one) 2',3'-dideoxyribonucleotide can be added to the 3'-end of a DNA fragment with calf thymus terminal transferase. Addition of more than one nucleotide analog per strand is impossible due to the absence of a 3'-terminal hydroxyl group. If the terminatind dideoxyribonucleotide contains an (alpha 32p) label, the resulting 3'-blocked strand can be digested by \"nearest neighbor\" techniques and the original 3'-endgroup determined. Picomole quantities of DNA strands can be labeled and the 3'-end determined."} {"id": "PMID:165469", "title": "Antiviral activity of polynucleotides: copolymers of inosinic acid and N2-dimethylguanylic of 2-methylthioinosinic acid.", "content": "Complexes of poly(C) with copolymers of inosinic acid containing various amounts of mismatched bases (see journal for formula) have been examined for direct resistance to virus infection, interferon induction and toxicity in two different cell cultures (primary rabbit kidney cells and mouse L-929 cells). Complexes in which 20% of the hypoxanthine bases were replaced by (see journal for formula) or ms-2I were partially active whereas complexes in which 40% or more of the hypoxanthine bases were replaced by the odd bases were entirely inactive. The decrease in biological activity observed upon intrusion of (see journal for formula) or ms-2I in the poly(I) strand of poly(I) with poly(C) closely paralleled the amount of odd bases introduced irrespective of the system employed to assess the biological activity (resistance to virus infection, interferon induction or toxicity).", "contents": "Antiviral activity of polynucleotides: copolymers of inosinic acid and N2-dimethylguanylic of 2-methylthioinosinic acid. Complexes of poly(C) with copolymers of inosinic acid containing various amounts of mismatched bases (see journal for formula) have been examined for direct resistance to virus infection, interferon induction and toxicity in two different cell cultures (primary rabbit kidney cells and mouse L-929 cells). Complexes in which 20% of the hypoxanthine bases were replaced by (see journal for formula) or ms-2I were partially active whereas complexes in which 40% or more of the hypoxanthine bases were replaced by the odd bases were entirely inactive. The decrease in biological activity observed upon intrusion of (see journal for formula) or ms-2I in the poly(I) strand of poly(I) with poly(C) closely paralleled the amount of odd bases introduced irrespective of the system employed to assess the biological activity (resistance to virus infection, interferon induction or toxicity)."} {"id": "PMID:165470", "title": "The public health nurse in mental health follow-up care.", "content": "To discover if psychiatric patients who received follow-up care in the home by public health nurses could assume a functional role in the family. and in the community to a greater extent than similar patients who did not receive home care, a sample of all chronic undifferentiated and paranoid schizophrenics who had been released from a Georgia mental hospital within a one-year period and who were receiving follow-up care in the home by the public health nurse was selected from County A and matched according to diagnosis, time released from the hospital, age, sex, race, income, education, and marital status as closely as possible with a sample of patients from County B who were not receiving such follow-up care. Eight pairs of patients were interviewed and rated according to the Psychiatric Status Schedule; six pairs of patients were rated on a questionnaire by a significant member of the family as to the amount of burden they imposed on the family. The rate of patients readmitted to the hospital was also calculated for each sample group and compared. No statistically significant differences were found in the readmission rate, functioning level in the family and the community, or burden on the family", "contents": "The public health nurse in mental health follow-up care. To discover if psychiatric patients who received follow-up care in the home by public health nurses could assume a functional role in the family. and in the community to a greater extent than similar patients who did not receive home care, a sample of all chronic undifferentiated and paranoid schizophrenics who had been released from a Georgia mental hospital within a one-year period and who were receiving follow-up care in the home by the public health nurse was selected from County A and matched according to diagnosis, time released from the hospital, age, sex, race, income, education, and marital status as closely as possible with a sample of patients from County B who were not receiving such follow-up care. Eight pairs of patients were interviewed and rated according to the Psychiatric Status Schedule; six pairs of patients were rated on a questionnaire by a significant member of the family as to the amount of burden they imposed on the family. The rate of patients readmitted to the hospital was also calculated for each sample group and compared. No statistically significant differences were found in the readmission rate, functioning level in the family and the community, or burden on the family"} {"id": "PMID:165476", "title": "[The functional state of the hypothalamo-hypophyseal system in tumors of the pituitary and diencephalic area].", "content": "A study was made of 38 persons, including 25--with acromegaly, 5--with chromophobic adenomas of the hypophysis, 3--with diencephalic tumours and 5 healthy individuals. STH, TTH and ACTH were determined in the blood plasma with the aid of radioimmunological methods under basic conditions and L-DOPA loading (10 mg per 1 kg of weight) with insulin (0.10 U/kg). There was an increase in the plasma content of STH, TTH and ACTH with a maximum 60 min after the administration of L-DOPA. In the patients with acromegaly STH increased considerably, and in cases with chromophobic adenomas and diencephalic tumours--less. ACTH level was also elevated. STH and ACTH level rose after insulin hypoglycemia. Possible mechanisms of a stimulating action of L-DOPA and insulin are discussed.", "contents": "[The functional state of the hypothalamo-hypophyseal system in tumors of the pituitary and diencephalic area]. A study was made of 38 persons, including 25--with acromegaly, 5--with chromophobic adenomas of the hypophysis, 3--with diencephalic tumours and 5 healthy individuals. STH, TTH and ACTH were determined in the blood plasma with the aid of radioimmunological methods under basic conditions and L-DOPA loading (10 mg per 1 kg of weight) with insulin (0.10 U/kg). There was an increase in the plasma content of STH, TTH and ACTH with a maximum 60 min after the administration of L-DOPA. In the patients with acromegaly STH increased considerably, and in cases with chromophobic adenomas and diencephalic tumours--less. ACTH level was also elevated. STH and ACTH level rose after insulin hypoglycemia. Possible mechanisms of a stimulating action of L-DOPA and insulin are discussed."} {"id": "PMID:165480", "title": "Induction of erythroid differentiation in murine virus infected eythroleukemia cells by highly polar compounds.", "content": "Murine-virus-infected erythroleukemia cells cultured in a medium with dimethylsulfoxide or N,N-dimethylformamide are induced to differentiate to erythroid cells. A number of highly polar compounds have a similar effect in inducing erythroid differentiation of the virus-infected cells, as assayed by the appearance of hemoglobin. These compounds are 1-methyl-1-2-piperidone, N,N-dimethylacetamide, N-methylpyrrolidinone, N-methylacetamide, 2-pyrrolidinone, propionamide, pyridine-N-oxide, piperidone, N-methylformamide, acetamide, and triethylene glycol. It has been previously reported that dimethylsulfoxide must be present during DNA synthesis and, possibly, shortly therafter, to induce differentiation. These findings are consistent with the hypothesis that dimethylsulfoxide and related polar compounds act by changing the conformation of DNA or a DNA-protein complex, causing an alteration in transcription that leads to the expression of the program of erythroid differentiation.", "contents": "Induction of erythroid differentiation in murine virus infected eythroleukemia cells by highly polar compounds. Murine-virus-infected erythroleukemia cells cultured in a medium with dimethylsulfoxide or N,N-dimethylformamide are induced to differentiate to erythroid cells. A number of highly polar compounds have a similar effect in inducing erythroid differentiation of the virus-infected cells, as assayed by the appearance of hemoglobin. These compounds are 1-methyl-1-2-piperidone, N,N-dimethylacetamide, N-methylpyrrolidinone, N-methylacetamide, 2-pyrrolidinone, propionamide, pyridine-N-oxide, piperidone, N-methylformamide, acetamide, and triethylene glycol. It has been previously reported that dimethylsulfoxide must be present during DNA synthesis and, possibly, shortly therafter, to induce differentiation. These findings are consistent with the hypothesis that dimethylsulfoxide and related polar compounds act by changing the conformation of DNA or a DNA-protein complex, causing an alteration in transcription that leads to the expression of the program of erythroid differentiation."} {"id": "PMID:165477", "title": "[A comparative analysis of the behavior of two labeled ACTH preparations in the body].", "content": "Experiments were conducted on male Wistar rats. A study was made of the intensity of incorporation into the liver, kidneys, the thyroid gland, the adrenal glands and the rate of elimination from the blood plasma of two ACTH preparations iodated by Greenwood's method: International Standard for Corticotropin, Mill Hill, London; Hum ACTH--Hid-28, Richter. It appeared that the preparations of natural swine -125-I-ACTH and of synthetic -131-I-ACTH were identical chromatographically and by saturation with iodine-125 and iodine-131, respectively, but differed by their behaviour in the organism. T1/2 for -125-I-ACTH (swine) was 4.7 min; the hormone was not incorporated into hepatic parenchyma, and only very weakly--into the kidneys, but it was intensively accumulated by the adrenal galnds. Radioactivity peak was recorded in the adrenal cortex 6 minutes after the administration of the labeled hormone. -131-I-ACTH (synthetic) disappeared from the blood with a falf-period of 11.2 min, was incorporated into the liver and particularly into the kidneys, and was not accumulated in the adrenal gland.", "contents": "[A comparative analysis of the behavior of two labeled ACTH preparations in the body]. Experiments were conducted on male Wistar rats. A study was made of the intensity of incorporation into the liver, kidneys, the thyroid gland, the adrenal glands and the rate of elimination from the blood plasma of two ACTH preparations iodated by Greenwood's method: International Standard for Corticotropin, Mill Hill, London; Hum ACTH--Hid-28, Richter. It appeared that the preparations of natural swine -125-I-ACTH and of synthetic -131-I-ACTH were identical chromatographically and by saturation with iodine-125 and iodine-131, respectively, but differed by their behaviour in the organism. T1/2 for -125-I-ACTH (swine) was 4.7 min; the hormone was not incorporated into hepatic parenchyma, and only very weakly--into the kidneys, but it was intensively accumulated by the adrenal galnds. Radioactivity peak was recorded in the adrenal cortex 6 minutes after the administration of the labeled hormone. -131-I-ACTH (synthetic) disappeared from the blood with a falf-period of 11.2 min, was incorporated into the liver and particularly into the kidneys, and was not accumulated in the adrenal gland."} {"id": "PMID:165481", "title": "Host induced alteration of avian sarcoma virus B-77 genome.", "content": "The genome of an avian oncornavirus was altered after infection of a heterologous host. This was studied with avian sarcoma virus B-77 in duck embryonic fibroblasts (DEF) and chicken embryonic fibroblasts (CEF). To detect alteration of the viral genome, we hybridized 35S B-77 RNA with normal duck DNA by either one of two techniques:when viral RNA was in excess and when DNA was in excess. The RNA of B-77 passaged only in gs minus chf minus CEF does not have homology with duck DNA. However, after several passages of B-77 through DEF the viral genome acquired duck specific RNA sequences. After 4 and 10 passages, B-77 RNA acquired 2.2 and 6.6%, respectively, complementarity to normal duck DNA. The duck specific RNA sequences were found to be covalently linked to the B-77 RNA genome. Also, the host specific sequences acquired by the virus appear to be from a region of the duck DNA which is repeated four to six times per cell. After 5 back passages in CEF some of the duck specific RNA sequences in the viral genome were lost.", "contents": "Host induced alteration of avian sarcoma virus B-77 genome. The genome of an avian oncornavirus was altered after infection of a heterologous host. This was studied with avian sarcoma virus B-77 in duck embryonic fibroblasts (DEF) and chicken embryonic fibroblasts (CEF). To detect alteration of the viral genome, we hybridized 35S B-77 RNA with normal duck DNA by either one of two techniques:when viral RNA was in excess and when DNA was in excess. The RNA of B-77 passaged only in gs minus chf minus CEF does not have homology with duck DNA. However, after several passages of B-77 through DEF the viral genome acquired duck specific RNA sequences. After 4 and 10 passages, B-77 RNA acquired 2.2 and 6.6%, respectively, complementarity to normal duck DNA. The duck specific RNA sequences were found to be covalently linked to the B-77 RNA genome. Also, the host specific sequences acquired by the virus appear to be from a region of the duck DNA which is repeated four to six times per cell. After 5 back passages in CEF some of the duck specific RNA sequences in the viral genome were lost."} {"id": "PMID:165478", "title": "[The effect of estrogens on the concentration of estradiol receptors in rat uterus, kidneys and liver].", "content": "The concentration of receptors to E2 decreased in the uterine cytoplasm of rat uterus and increased in the nuclei during sexual maturation. With ageing this index in the cytoplasm and the nuclei of the uterus fell, and failed to alter during pregnancy. After ovariectomy the concentration of the receptors increased in the uterine cytoplasm, but no marked changes in the receptors occurred in the nuclei. No significant changes were revealed in the receptors to E2 in sexual maturation, pregnancy and ovariectomy in the cytoplasm and the nuclei of the kidneys and the liver. Administration to rats of E2 produced a reduction of the concentration of receptors to E2 in the cytoplasm of the uterus, kidneys and the liver and an increase in their content in the nuclei of the uterus and the liver.", "contents": "[The effect of estrogens on the concentration of estradiol receptors in rat uterus, kidneys and liver]. The concentration of receptors to E2 decreased in the uterine cytoplasm of rat uterus and increased in the nuclei during sexual maturation. With ageing this index in the cytoplasm and the nuclei of the uterus fell, and failed to alter during pregnancy. After ovariectomy the concentration of the receptors increased in the uterine cytoplasm, but no marked changes in the receptors occurred in the nuclei. No significant changes were revealed in the receptors to E2 in sexual maturation, pregnancy and ovariectomy in the cytoplasm and the nuclei of the kidneys and the liver. Administration to rats of E2 produced a reduction of the concentration of receptors to E2 in the cytoplasm of the uterus, kidneys and the liver and an increase in their content in the nuclei of the uterus and the liver."} {"id": "PMID:165479", "title": "[Stimulation of the protein synthesizing capacity of thyroid gland polyribosomes in vitro under the influence of cyclic adenosine-3', 5'-monophosphate].", "content": "It was shown that cAMP increased the capacity of polyribosomes of the thyroid glands to the labeled phenylalanine incorporation into the protein by 51 per cent. Preincubation of microsomes or ribosomes with cAMP in the cell-free protein-synthesizing system also increased the incorporation of the labeled amino acids into the protein by 54 and 49 per cent, respectively. The optimal effect occurred with the concentration of cAMP of 0.2 mg/ml. cAMP in a concentration of 0.8 mg/ml inhibited the incorporation of the labeled amino acids by 32 per cent. This can possibly be attributed to the forming products of cAMP degradation. Modification of the protein-synthesizing system (ATP--1 mM. GTP--1.6 mM) led to the fact of an increase in the level of the labeled amino acid incorporation into the protein by 54 per cent; the simulating effect of cAMP persisted. In the absence of ATP in the incubation medium addition of cAMP failed to stimulate the protein synthesis. Thus, cAMP stimulated protein synthesis in the thyroid gland in vitro, with utilization of ribonucleoproteid particles.", "contents": "[Stimulation of the protein synthesizing capacity of thyroid gland polyribosomes in vitro under the influence of cyclic adenosine-3', 5'-monophosphate]. It was shown that cAMP increased the capacity of polyribosomes of the thyroid glands to the labeled phenylalanine incorporation into the protein by 51 per cent. Preincubation of microsomes or ribosomes with cAMP in the cell-free protein-synthesizing system also increased the incorporation of the labeled amino acids into the protein by 54 and 49 per cent, respectively. The optimal effect occurred with the concentration of cAMP of 0.2 mg/ml. cAMP in a concentration of 0.8 mg/ml inhibited the incorporation of the labeled amino acids by 32 per cent. This can possibly be attributed to the forming products of cAMP degradation. Modification of the protein-synthesizing system (ATP--1 mM. GTP--1.6 mM) led to the fact of an increase in the level of the labeled amino acid incorporation into the protein by 54 per cent; the simulating effect of cAMP persisted. In the absence of ATP in the incubation medium addition of cAMP failed to stimulate the protein synthesis. Thus, cAMP stimulated protein synthesis in the thyroid gland in vitro, with utilization of ribonucleoproteid particles."} {"id": "PMID:165483", "title": "Interaction of a spin-labeled long chain acylcholine with the cholinergic receptor protein in its membrane environment.", "content": "The choline ester of a spin-labeled fatty acid, 8-doxylpalmitocylcholine, CH3--(CH2)7--CR-(CH2)6-- + COO--(CH2)2--N(CH3)3, where R is the paramagnetic 4',4'-dimethyloxazolidine-N-oxyl (doxyl) ring has been synthesized. 8-Doxylpalmitoylcholine blocks reversibly the depolarization of Electrophorus electroplaque elicited by the bath application of carbamylcholine. It slows down the initial rate of binding of the alpha-[3-H]toxin from Naja nigricollis to receptor-rich membranes fragments from Torpedo, and it displaces [3-H]acetylcholine bound to the cholinergic receptor site present in these fragments. Electron spin resonance spectra of 8-doxylpalmitoylcholine in the presence of the receptor-rich membrane fragments show complete immobilization of the spin label. Various cholinergic agents tested, including N. nigricollis alpha-toxin, reverse this immobilization, probably by displacing the 8-doxylpalmitoylcholine from its complex with the cholinergic receptor protein to the lipid phase of the membrane.", "contents": "Interaction of a spin-labeled long chain acylcholine with the cholinergic receptor protein in its membrane environment. The choline ester of a spin-labeled fatty acid, 8-doxylpalmitocylcholine, CH3--(CH2)7--CR-(CH2)6-- + COO--(CH2)2--N(CH3)3, where R is the paramagnetic 4',4'-dimethyloxazolidine-N-oxyl (doxyl) ring has been synthesized. 8-Doxylpalmitoylcholine blocks reversibly the depolarization of Electrophorus electroplaque elicited by the bath application of carbamylcholine. It slows down the initial rate of binding of the alpha-[3-H]toxin from Naja nigricollis to receptor-rich membranes fragments from Torpedo, and it displaces [3-H]acetylcholine bound to the cholinergic receptor site present in these fragments. Electron spin resonance spectra of 8-doxylpalmitoylcholine in the presence of the receptor-rich membrane fragments show complete immobilization of the spin label. Various cholinergic agents tested, including N. nigricollis alpha-toxin, reverse this immobilization, probably by displacing the 8-doxylpalmitoylcholine from its complex with the cholinergic receptor protein to the lipid phase of the membrane."} {"id": "PMID:165482", "title": "Cyclic AMP and cyclic GMP concentrations in serum- and density-restricted fibroblast cultures.", "content": "Mouse fibroblasts transformed by simian virus 40 (SV3T3 cells) are characterized by cyclic AMP and cyclic GMP levels, respectively, about half and twice those found in growing untransformed 3T3 cells. Density-dependent inhibition of growth is correlated with reduced cyclic GMP concentrations in 3T3 and four different density-restricted revertant lines derived from SV3T3. The levels of cyclic AMP are not increased at confluence. Upon serum restriction, serum-dependent cell lines show a greater increase in intracellular cAMP than serum-insensitive lines. Cyclic GMP levels are greatly reduced, even in serum-insensitive density revertants, but not in SV3T3. Serum readdition to all serum-dependent lines is followed by a rapid decrease in cyclic AMP and increase in cyclic GMP concentrations. The magnitude of these responses is decreased in SV3T3 and density revertants.", "contents": "Cyclic AMP and cyclic GMP concentrations in serum- and density-restricted fibroblast cultures. Mouse fibroblasts transformed by simian virus 40 (SV3T3 cells) are characterized by cyclic AMP and cyclic GMP levels, respectively, about half and twice those found in growing untransformed 3T3 cells. Density-dependent inhibition of growth is correlated with reduced cyclic GMP concentrations in 3T3 and four different density-restricted revertant lines derived from SV3T3. The levels of cyclic AMP are not increased at confluence. Upon serum restriction, serum-dependent cell lines show a greater increase in intracellular cAMP than serum-insensitive lines. Cyclic GMP levels are greatly reduced, even in serum-insensitive density revertants, but not in SV3T3. Serum readdition to all serum-dependent lines is followed by a rapid decrease in cyclic AMP and increase in cyclic GMP concentrations. The magnitude of these responses is decreased in SV3T3 and density revertants."} {"id": "PMID:165484", "title": "Plasminogen-independent fibrinolysis by proteases produced by transformed chick embryo fibroblasts.", "content": "The fibrinolytic activity of proteases secreted by chick embryo fibroblasts infected with Rous sarcoma virus was studied by use of a procedure in which a fibrin clot was formed with highly purified fibrinogen and thrombin above the cell layer. This procedure results in the formation of fibrin that is apparently a more suitable substrate for studies on fibrinolysis than is fibrin prepared by other methods. Since neither plasminogen nor serum were included in the assay system in the present studies, the fibrinolytic activity observed cannot be ascribed to the conversion of the plasminogen in serum to plasmin by a plasminogen activator produced by transformed cells. Our procedure, therefore, measures proteolytic activities other than those reported by previous investigators. Maintenance of some of the transformed phenotypes of Rous sarcoma virus transformed chick embryo fibroblasts such as morpholigical change and increased rate of glucose uptake apparently does not depend on the presence of plasminogen in the culture medium.", "contents": "Plasminogen-independent fibrinolysis by proteases produced by transformed chick embryo fibroblasts. The fibrinolytic activity of proteases secreted by chick embryo fibroblasts infected with Rous sarcoma virus was studied by use of a procedure in which a fibrin clot was formed with highly purified fibrinogen and thrombin above the cell layer. This procedure results in the formation of fibrin that is apparently a more suitable substrate for studies on fibrinolysis than is fibrin prepared by other methods. Since neither plasminogen nor serum were included in the assay system in the present studies, the fibrinolytic activity observed cannot be ascribed to the conversion of the plasminogen in serum to plasmin by a plasminogen activator produced by transformed cells. Our procedure, therefore, measures proteolytic activities other than those reported by previous investigators. Maintenance of some of the transformed phenotypes of Rous sarcoma virus transformed chick embryo fibroblasts such as morpholigical change and increased rate of glucose uptake apparently does not depend on the presence of plasminogen in the culture medium."} {"id": "PMID:165485", "title": "Affinity chromatography of viral DNA polymerases on pyran-sepharose.", "content": "Pyran covalently linked to cyanogen bromide-activated Sepharose has been shown to be an effective affinity matrix for several viral DNA polymerases. Differential salt elution of viral compared with cellular polymerases, as well as substrate elution, suggests the affinity nature for the matrix. Unlike some other affinity systems described, pyran-Sepharose is totally resistant to nuclease digestion and is stable at 4 degrees for several months. DNA polymerases isolated from several viruses by detergent treatment were recovered in good yield. Analysis of iodinated proteins by sodium dodecyl sulfate-gel electrophoresis revealed that the DNA polymerase of avian myeloblastosis virus found in crude preparations of the virus could be purified nearly to homogeneity by a single passage through the column. These results suggest that pyran-Sepharose is an effective affinity column that is potentially adaptable as part of a general purification procedure for viral DNA polymerases.", "contents": "Affinity chromatography of viral DNA polymerases on pyran-sepharose. Pyran covalently linked to cyanogen bromide-activated Sepharose has been shown to be an effective affinity matrix for several viral DNA polymerases. Differential salt elution of viral compared with cellular polymerases, as well as substrate elution, suggests the affinity nature for the matrix. Unlike some other affinity systems described, pyran-Sepharose is totally resistant to nuclease digestion and is stable at 4 degrees for several months. DNA polymerases isolated from several viruses by detergent treatment were recovered in good yield. Analysis of iodinated proteins by sodium dodecyl sulfate-gel electrophoresis revealed that the DNA polymerase of avian myeloblastosis virus found in crude preparations of the virus could be purified nearly to homogeneity by a single passage through the column. These results suggest that pyran-Sepharose is an effective affinity column that is potentially adaptable as part of a general purification procedure for viral DNA polymerases."} {"id": "PMID:165486", "title": "Stimulation of DNA polymerase by factors isolated from Novikoff hepatoma.", "content": "Extracts of Novikoff hepatoma cells contain factors capable of stimulating in vitro DNA synthesis several fold. The activity can be resolved into three separate protein peaks on DEAE-Sephadex. Two of these, factors II and III, have been purified and partially characterized. Both factors increase the initial rate of DNA synthesis and allow synthesis to proceed much longer. If either factor is added after synthesis by the DNA polymerase has reached a plateau, resumption of synthesis occurs. The factors appear to have different modes of action or sites of action since they show an additive effect even when a single one is used at saturating conditions. These factors are present in normal rat liver but at a concentration less than 5% of that found in the tumor cells. When tested with several highly purified DNA polymerases (DNA nucleotidyltransferase, EC 2.7.7.7), the factors show a much greater stimulation of homologous, non-mitochondrial enzymes (rat liver nuclear-, rat liver cytoplasmic-, or Novikoff-DNA polymerases) when compared with rat liver or calf liver mitochondrial-, Escherichia coli I-, or sea urchin nuclear-DNA polymerases. The mechanism of action of these factors is not known at present. No enzymatic activity has been associated with factor III. Highly purified, but not homogeneous, preparations of factor II contain low levels of endonuclease; it has not been established whether endonuclease is a contaminant or is responsible for the stimulating activity.", "contents": "Stimulation of DNA polymerase by factors isolated from Novikoff hepatoma. Extracts of Novikoff hepatoma cells contain factors capable of stimulating in vitro DNA synthesis several fold. The activity can be resolved into three separate protein peaks on DEAE-Sephadex. Two of these, factors II and III, have been purified and partially characterized. Both factors increase the initial rate of DNA synthesis and allow synthesis to proceed much longer. If either factor is added after synthesis by the DNA polymerase has reached a plateau, resumption of synthesis occurs. The factors appear to have different modes of action or sites of action since they show an additive effect even when a single one is used at saturating conditions. These factors are present in normal rat liver but at a concentration less than 5% of that found in the tumor cells. When tested with several highly purified DNA polymerases (DNA nucleotidyltransferase, EC 2.7.7.7), the factors show a much greater stimulation of homologous, non-mitochondrial enzymes (rat liver nuclear-, rat liver cytoplasmic-, or Novikoff-DNA polymerases) when compared with rat liver or calf liver mitochondrial-, Escherichia coli I-, or sea urchin nuclear-DNA polymerases. The mechanism of action of these factors is not known at present. No enzymatic activity has been associated with factor III. Highly purified, but not homogeneous, preparations of factor II contain low levels of endonuclease; it has not been established whether endonuclease is a contaminant or is responsible for the stimulating activity."} {"id": "PMID:165487", "title": "Methylation-dependent translation of viral messenger RNAs in vitro.", "content": "Methylated reovirus and vesicular stomatitis virus mRNAs, synthesized in vitro in the presence of S-adenosylmethionine by the virion-associated polymerases (RNA nucleotidyltransferases, EC 2.7.7.6), stimulate protein synthesis by wehat germ extracts to a greater extent than unmethylated mRNAs. Addition of S-adenosylmethionine to a cell-free extract programmed with unmethylated mRNA stimulates protein synthesis and results in methylation of the mRNA. An inhibitor of mRNA methylation. S-adenosylhomocysteine, blocks translation of unmethylated, but not of methylated, mRNAs. Aurintricarboxylic acid, which inhibits polypepetide chain initiation, also prevents mRNA methylation by wheat germ extracts. In contrast, sparsomycin, which inhibits polypeptide chain elongation, does not reduce mRNA methylation. The results indicate that methylation of viral mRNA is required for translation in vitro and suggest that mRNA methylation occurs at the initiation step of protein synthesis.", "contents": "Methylation-dependent translation of viral messenger RNAs in vitro. Methylated reovirus and vesicular stomatitis virus mRNAs, synthesized in vitro in the presence of S-adenosylmethionine by the virion-associated polymerases (RNA nucleotidyltransferases, EC 2.7.7.6), stimulate protein synthesis by wehat germ extracts to a greater extent than unmethylated mRNAs. Addition of S-adenosylmethionine to a cell-free extract programmed with unmethylated mRNA stimulates protein synthesis and results in methylation of the mRNA. An inhibitor of mRNA methylation. S-adenosylhomocysteine, blocks translation of unmethylated, but not of methylated, mRNAs. Aurintricarboxylic acid, which inhibits polypepetide chain initiation, also prevents mRNA methylation by wheat germ extracts. In contrast, sparsomycin, which inhibits polypeptide chain elongation, does not reduce mRNA methylation. The results indicate that methylation of viral mRNA is required for translation in vitro and suggest that mRNA methylation occurs at the initiation step of protein synthesis."} {"id": "PMID:165488", "title": "Physical properties of New Jersey serotype of vesicular stomatitis virus and its defective particles.", "content": "The wild-type New Jersey serotype of vesicular stomatitis virus generated two types of defective interfering T-particles. The physical properties of these particles and the wild-type virion were determined by laser light scattering spectroscopy, sedimentation measurements, and electron microscopy.", "contents": "Physical properties of New Jersey serotype of vesicular stomatitis virus and its defective particles. The wild-type New Jersey serotype of vesicular stomatitis virus generated two types of defective interfering T-particles. The physical properties of these particles and the wild-type virion were determined by laser light scattering spectroscopy, sedimentation measurements, and electron microscopy."} {"id": "PMID:165489", "title": "Lack of detectable change in cyclic AMP during the cardiac inotropic response to isoproterenol immobilized on glass beads.", "content": "Changes in contractility and the levels of adenosine 3':5'-cyclic monophosphoric acid (cAMP) were assessed in isolated cat cardiac muscle in response to soluble isoproterenol and isoproterenol immobilized on glass beads. Drug-induced positive inotropic responses were compared to the maximum isometric force achieved with paired electrical stimulation, a potent physiological inotropic stimulus. Isoproterenol (1 muM) in solution increased the force of contraction 0.832 plus or minus 0.165 g at 60 sec in eight muscles tested, which at 60 and 120 sec averaged 65.5 plus or minus 6.5% and 82.9 plus or minus 8.8%, respectively, of the force with paired electrical stimulation. Isoproterenol immobilized on glass beads gave positive inotropic responses similar to those for the soluble form of the drug. Placement of only three isoproterenol-glass beads on the muscles increased the force of contraction 0.742 plus or minus 0.166 g at 60 sec (n equals 11), which at 60 and 120 sec averaged 45.1 plus or minus 7.0% and 58.6 plus or minus 6.4%, respectively, of the force with paired electrical stimulation. The magnitude of this response indicates that the increased force was developed by at least 60% of the cells in each muscle. Control levels of cAMP were 0.527 plus or minus 0.049 pmol/mg of tissue wet weight, n equals 11. cAMP levels 60 sec after 1 muM soluble isoproterenol was added were 1.212 plus or minus 0.085 pmol/mg; in contrast, the levels of cAMP in response to isoproterenol immobilized on glass beads at 60 sec were 0.490 plus or minus 0.060 pmol/mg, not significantly different from control levels. These data indicate that cAMP may not be involved in the propagation of the inotropic response that must have occurred in these cardiac muscles and raise questions as to the physiological significance of the large cAMP increases that occur in response to soluble drugs and hormones.", "contents": "Lack of detectable change in cyclic AMP during the cardiac inotropic response to isoproterenol immobilized on glass beads. Changes in contractility and the levels of adenosine 3':5'-cyclic monophosphoric acid (cAMP) were assessed in isolated cat cardiac muscle in response to soluble isoproterenol and isoproterenol immobilized on glass beads. Drug-induced positive inotropic responses were compared to the maximum isometric force achieved with paired electrical stimulation, a potent physiological inotropic stimulus. Isoproterenol (1 muM) in solution increased the force of contraction 0.832 plus or minus 0.165 g at 60 sec in eight muscles tested, which at 60 and 120 sec averaged 65.5 plus or minus 6.5% and 82.9 plus or minus 8.8%, respectively, of the force with paired electrical stimulation. Isoproterenol immobilized on glass beads gave positive inotropic responses similar to those for the soluble form of the drug. Placement of only three isoproterenol-glass beads on the muscles increased the force of contraction 0.742 plus or minus 0.166 g at 60 sec (n equals 11), which at 60 and 120 sec averaged 45.1 plus or minus 7.0% and 58.6 plus or minus 6.4%, respectively, of the force with paired electrical stimulation. The magnitude of this response indicates that the increased force was developed by at least 60% of the cells in each muscle. Control levels of cAMP were 0.527 plus or minus 0.049 pmol/mg of tissue wet weight, n equals 11. cAMP levels 60 sec after 1 muM soluble isoproterenol was added were 1.212 plus or minus 0.085 pmol/mg; in contrast, the levels of cAMP in response to isoproterenol immobilized on glass beads at 60 sec were 0.490 plus or minus 0.060 pmol/mg, not significantly different from control levels. These data indicate that cAMP may not be involved in the propagation of the inotropic response that must have occurred in these cardiac muscles and raise questions as to the physiological significance of the large cAMP increases that occur in response to soluble drugs and hormones."} {"id": "PMID:165490", "title": "Epithelial cell death and cyclic AMP increase during palatal development.", "content": "Cyclic AMP levels increase abruptly in the secondary palatal shelf (mesenchyme plus a two- to three-cell-layered epithelium) between day 15 and 16 of gestation in the rat embryo. The addition of dibutyryl cyclic AMP to the media in which immature palatal shelves (day 14) are cultured causes a precocious decrease in DNA synthesis, but increased glycoprotein synthesis and epithelial adhesiveness. These changes are most evident in the medial-edge epithelial cells and resemble the developmental events that occur normally on day 15 and 16 during formation of the secondary palate. The initiation of epithelial cell death and adhesiveness in the medial edge of the palatal shelf may be mediated through an increase in cyclic AMP.", "contents": "Epithelial cell death and cyclic AMP increase during palatal development. Cyclic AMP levels increase abruptly in the secondary palatal shelf (mesenchyme plus a two- to three-cell-layered epithelium) between day 15 and 16 of gestation in the rat embryo. The addition of dibutyryl cyclic AMP to the media in which immature palatal shelves (day 14) are cultured causes a precocious decrease in DNA synthesis, but increased glycoprotein synthesis and epithelial adhesiveness. These changes are most evident in the medial-edge epithelial cells and resemble the developmental events that occur normally on day 15 and 16 during formation of the secondary palate. The initiation of epithelial cell death and adhesiveness in the medial edge of the palatal shelf may be mediated through an increase in cyclic AMP."} {"id": "PMID:165491", "title": "Cyclic AMP, a nonessential regulator of the cell cycle.", "content": "Flow-microfluorimetric analysis has been carried out on populations of exponentially growing S49 mouse lymphoma cells treated with dibutyryl cyclic AMP. The drug produces a specific concentration-dependent block in the G-1 phase of the cell cycle while other phases of the cycle are not perceptibly altered. The cell cycle of a line of mutant cells lacking the cyclic AMP-dependent protein kinase is not affected by the drug. Since these mutant cells have been shown to maintain a normal cell cycle, even in the presence of high levels of cyclic AMP, periodic fluctuations in the levels of the cyclic nucleotide cannot be required for or determine progression through the cell cycle.", "contents": "Cyclic AMP, a nonessential regulator of the cell cycle. Flow-microfluorimetric analysis has been carried out on populations of exponentially growing S49 mouse lymphoma cells treated with dibutyryl cyclic AMP. The drug produces a specific concentration-dependent block in the G-1 phase of the cell cycle while other phases of the cycle are not perceptibly altered. The cell cycle of a line of mutant cells lacking the cyclic AMP-dependent protein kinase is not affected by the drug. Since these mutant cells have been shown to maintain a normal cell cycle, even in the presence of high levels of cyclic AMP, periodic fluctuations in the levels of the cyclic nucleotide cannot be required for or determine progression through the cell cycle."} {"id": "PMID:165492", "title": "Cyclic AMP and immune responses: changes in the splenic level of cyclic AMP during the response of mice to antigen.", "content": "Intravenous injection of sheep erythrocytes into normal immunologically competent C57BL/6J mice results in significant and characteristic changes in the splenic level of 3':5'-cAMP with initiation of the immune response and proliferation of antibody-forming cells. The level increases 2- to 3-fold initially, peaks at 2 min, and returns to base level in an hour. Between 2 and 5 days there is a decrease, followed by a peak when the rate of proliferation of antibody-forming cells is maximal. Changes in splenic level of cAMP are thus transitory and biphasic, and they occur only in response to foreign substances that are immunogenic, such as heterologous erythrocytes, and not to antigenically inert carbon particles. They are also dependent upon the dose of immunogen. Moreover, the double-stranded hybrid of polyadenylate and polyuridylate, which acts synergistically with antigen in stimulating endogenous cAMP, is immuno-enhancing if given with sheep erythrocytes when the cAMP level is increasing, and immunosuppresive if given when cAMP is decreasing. These data provide direct evidence for a role of cAMP as a mediator in the activation and proliferation of immunocytes stimulated by antigen. With knowledge of the transitory and biphasic nature of the cAMP response induced by antigen, one can avoid indiscriminate use of drugs that modify the level of endogenous cAMP and instead employ them rationally in controlling the immune response, enhancing or suppressing it as desired.", "contents": "Cyclic AMP and immune responses: changes in the splenic level of cyclic AMP during the response of mice to antigen. Intravenous injection of sheep erythrocytes into normal immunologically competent C57BL/6J mice results in significant and characteristic changes in the splenic level of 3':5'-cAMP with initiation of the immune response and proliferation of antibody-forming cells. The level increases 2- to 3-fold initially, peaks at 2 min, and returns to base level in an hour. Between 2 and 5 days there is a decrease, followed by a peak when the rate of proliferation of antibody-forming cells is maximal. Changes in splenic level of cAMP are thus transitory and biphasic, and they occur only in response to foreign substances that are immunogenic, such as heterologous erythrocytes, and not to antigenically inert carbon particles. They are also dependent upon the dose of immunogen. Moreover, the double-stranded hybrid of polyadenylate and polyuridylate, which acts synergistically with antigen in stimulating endogenous cAMP, is immuno-enhancing if given with sheep erythrocytes when the cAMP level is increasing, and immunosuppresive if given when cAMP is decreasing. These data provide direct evidence for a role of cAMP as a mediator in the activation and proliferation of immunocytes stimulated by antigen. With knowledge of the transitory and biphasic nature of the cAMP response induced by antigen, one can avoid indiscriminate use of drugs that modify the level of endogenous cAMP and instead employ them rationally in controlling the immune response, enhancing or suppressing it as desired."} {"id": "PMID:165493", "title": "Binding of ATP to the progesterone receptor.", "content": "The possible interaction of progesterone--receptor complexes with nucleotides was tested by affinity chromatography. The cytosol progesterone receptor from hen oviduct was partially purified by ammonium sulfate precipitation before use. When progesterone was bound to the receptor, the resulting complex could be selectively adsorbed onto columns of ATP-Sepharose. This interaction was reversible and of an ionic nature since it could be disrupted by high-salt conditions. A competitive binding assay was used to test the specificity of receptor binding to several other nucleotides, including ADP, AMP, and cAMP. A clear specificity for binding ATP was evident from these studies. When ATP was added to receptor preparations, the nucleotide did not affect the sedimentation properties or hormone binding characteristics of the receptor. Although the function of ATP remains unknown, these studies indicate a role of this nucleotide in some aspect of hormone receptor activity.", "contents": "Binding of ATP to the progesterone receptor. The possible interaction of progesterone--receptor complexes with nucleotides was tested by affinity chromatography. The cytosol progesterone receptor from hen oviduct was partially purified by ammonium sulfate precipitation before use. When progesterone was bound to the receptor, the resulting complex could be selectively adsorbed onto columns of ATP-Sepharose. This interaction was reversible and of an ionic nature since it could be disrupted by high-salt conditions. A competitive binding assay was used to test the specificity of receptor binding to several other nucleotides, including ADP, AMP, and cAMP. A clear specificity for binding ATP was evident from these studies. When ATP was added to receptor preparations, the nucleotide did not affect the sedimentation properties or hormone binding characteristics of the receptor. Although the function of ATP remains unknown, these studies indicate a role of this nucleotide in some aspect of hormone receptor activity."} {"id": "PMID:165494", "title": "Structure-function relationships and mode of replication of animal rhabdoviruses.", "content": "Recently accumulated knowledge allows more precise comparison of the structural (and possibly evolutionary) relationships of several different animal rhabdoviruses: vesicular stomatitis virus, rabies virus, Kern Canyon virus, and spring viremia of carp virus. Each virus is composed primarily of a glycoprotein, an RNA-associated nucleoprotein, and one or two membrane proteins. Vesicular stomatitis virus group viruses contain lesser amounts of two additional distinct polypeptides, NS and L. The separate viruses undergo structural polypeptide phosphorylation in vivo according to characteristic patterns. In vesicular stomatitis virus the NS protein is selectively phosphorylated. In rabies group viruses and in spring viremia of carp virus, the nucleoprotein is the predominant phosphoprotein; in these viruses only the phosphorylated moiety is selectively cleaved off with trypsin. In Kern Canyon virus, only membrane protein and glycoprotein are weakly phosphorylated. Each virus possesses a virion-bound protein kinase. Vesicular stomatitis virus group viruses, Kern Canyon virus, and spring viremia of carp virus only contain virion-bound transcriptases of respectively decreasing levels of activity demonstrable in vitro. Vesicular stomatitis and Kern Canyon viruses replicate efficiently in enucleated cells; rabies virus does not. Based upon these observations, it is suggested that vesicular stomatitis virus may represent the most highly evolved of these rhabdoviruses, whereas spring viremia of carp and Kern Canyon viruses may represent \"evolutionary links\" between the vesicular stomatitis and rabies virus groups.", "contents": "Structure-function relationships and mode of replication of animal rhabdoviruses. Recently accumulated knowledge allows more precise comparison of the structural (and possibly evolutionary) relationships of several different animal rhabdoviruses: vesicular stomatitis virus, rabies virus, Kern Canyon virus, and spring viremia of carp virus. Each virus is composed primarily of a glycoprotein, an RNA-associated nucleoprotein, and one or two membrane proteins. Vesicular stomatitis virus group viruses contain lesser amounts of two additional distinct polypeptides, NS and L. The separate viruses undergo structural polypeptide phosphorylation in vivo according to characteristic patterns. In vesicular stomatitis virus the NS protein is selectively phosphorylated. In rabies group viruses and in spring viremia of carp virus, the nucleoprotein is the predominant phosphoprotein; in these viruses only the phosphorylated moiety is selectively cleaved off with trypsin. In Kern Canyon virus, only membrane protein and glycoprotein are weakly phosphorylated. Each virus possesses a virion-bound protein kinase. Vesicular stomatitis virus group viruses, Kern Canyon virus, and spring viremia of carp virus only contain virion-bound transcriptases of respectively decreasing levels of activity demonstrable in vitro. Vesicular stomatitis and Kern Canyon viruses replicate efficiently in enucleated cells; rabies virus does not. Based upon these observations, it is suggested that vesicular stomatitis virus may represent the most highly evolved of these rhabdoviruses, whereas spring viremia of carp and Kern Canyon viruses may represent \"evolutionary links\" between the vesicular stomatitis and rabies virus groups."} {"id": "PMID:165495", "title": "Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone.", "content": "Melanocyte stimulating hormone (MSH) enhances melanization but inhibits proliferation of Cloudman S91 melanoma cells in culture. We have isolated variants of these cells that can grow in the presence of MSH. The conclusions we have reached from analyses of these cells are the following: (1) Basal tyrosinase activity (monophenol monooxygenase; monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), i.e., the activity that is present in the absence of added MSH, is related through a common biochemical pathway to MSH-mediated control of growth. (2) MSH-inducible tyrosinase activity does not appear to be related to MSH control of growth. (3) The morphological changes that occur following the addition of MSH or cAMP are related to controls of growth and not to those of melanization.", "contents": "Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone. Melanocyte stimulating hormone (MSH) enhances melanization but inhibits proliferation of Cloudman S91 melanoma cells in culture. We have isolated variants of these cells that can grow in the presence of MSH. The conclusions we have reached from analyses of these cells are the following: (1) Basal tyrosinase activity (monophenol monooxygenase; monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), i.e., the activity that is present in the absence of added MSH, is related through a common biochemical pathway to MSH-mediated control of growth. (2) MSH-inducible tyrosinase activity does not appear to be related to MSH control of growth. (3) The morphological changes that occur following the addition of MSH or cAMP are related to controls of growth and not to those of melanization."} {"id": "PMID:165496", "title": "Free radicals formed by exposure of pyrimidine solids to sodium atoms: an electron spin resonance study.", "content": "Sodium atoms have been deposited on various pyrimidine powders under high vacuum at 77 degrees K and the electron spin resonance spectra of the resulting free radicals have been observed. Generally, the spectra show that the electron of the Na goes into a molecular orbital of the pyrimidine ring and the Na+ ions become attached to a carbonyl oxygen of the resulting pyrimidine anion. In 5-fluorouracil and 5-chlorouracil, however, the halogen is evidently abstracted by the Na to form NaF or NaC1 and the neutral uracil radical. Thymine shows evidence for H-addition radicals as well as the Na+-[thymine]-complex. The H source for the addition radicals may be an H-2-0 impurity in the sample, with which the Na atoms combine to release the H atoms. In addition to a resonance with g equals 2.00 from the pyrimidine anion radical, broad resonances with g greater than 2 were observed for 5-bromouracil, 5-chlorouracil and 5-iodouracil, as well as for alloxan and cytosine. These resonances, generally unstable at room temperature, are believed to arise from electrons trapped in interstitial sties or vacancies in the lattice.", "contents": "Free radicals formed by exposure of pyrimidine solids to sodium atoms: an electron spin resonance study. Sodium atoms have been deposited on various pyrimidine powders under high vacuum at 77 degrees K and the electron spin resonance spectra of the resulting free radicals have been observed. Generally, the spectra show that the electron of the Na goes into a molecular orbital of the pyrimidine ring and the Na+ ions become attached to a carbonyl oxygen of the resulting pyrimidine anion. In 5-fluorouracil and 5-chlorouracil, however, the halogen is evidently abstracted by the Na to form NaF or NaC1 and the neutral uracil radical. Thymine shows evidence for H-addition radicals as well as the Na+-[thymine]-complex. The H source for the addition radicals may be an H-2-0 impurity in the sample, with which the Na atoms combine to release the H atoms. In addition to a resonance with g equals 2.00 from the pyrimidine anion radical, broad resonances with g greater than 2 were observed for 5-bromouracil, 5-chlorouracil and 5-iodouracil, as well as for alloxan and cytosine. These resonances, generally unstable at room temperature, are believed to arise from electrons trapped in interstitial sties or vacancies in the lattice."} {"id": "PMID:165497", "title": "Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids.", "content": "We described previously a simple test on petri plates for detecting chemical carcinogens as mutagens, using an especially sensitive set of bacterial strains to detect mutagenic acitivty and a mammalian liver extract for carcinogen activity. We now extend the utility of the method by introducing two new bacterial strains which can detect with great sensitivity many carcinogens which we did not detect before or detected with less sensitivity. Among these carcinogens are aflatoxin B-1, sterigmatocystin, benzyl chloride, benzo[a]-pyrene, 7,12-dimethylbenzanthracene, 1'-acetoxysafrole, and the nitrofuran food additive furylfuramide (AF-2). The new strains TA100 and TA98 contain an R factor plasmid, pKM101, in our standard tester strains TA1535 and TA1538. The R factor increases mutagenesis with certain mutagens, but not others. We present evidence that the mutagens that become more effective work through an error-prone recombinational repair.", "contents": "Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. We described previously a simple test on petri plates for detecting chemical carcinogens as mutagens, using an especially sensitive set of bacterial strains to detect mutagenic acitivty and a mammalian liver extract for carcinogen activity. We now extend the utility of the method by introducing two new bacterial strains which can detect with great sensitivity many carcinogens which we did not detect before or detected with less sensitivity. Among these carcinogens are aflatoxin B-1, sterigmatocystin, benzyl chloride, benzo[a]-pyrene, 7,12-dimethylbenzanthracene, 1'-acetoxysafrole, and the nitrofuran food additive furylfuramide (AF-2). The new strains TA100 and TA98 contain an R factor plasmid, pKM101, in our standard tester strains TA1535 and TA1538. The R factor increases mutagenesis with certain mutagens, but not others. We present evidence that the mutagens that become more effective work through an error-prone recombinational repair."} {"id": "PMID:165498", "title": "Biochemical method for mapping mutational alterations in DNA with S1 nuclease: the location of deletions and temperature-sensitive mutations in simian virus 40.", "content": "S1 nuclease (EC 3.1.4.X), a single-strand-specific nuclease, can be used to accurately map the location of mutational alterations in simian virus 40 (SV40) DNA. Deletions of between 32 and 190 base pairs, which are at or below the limit of detectability by conventional electron microscopic analysis of heteroduplex DNAs, have been located in this way. To map a deletion, a mixture of unit length, linear DNA, prepared from the SV40 deletion mutant and its wild-type parent, are denatured and reannealed to form heteroduplexes. S1 nuclease can cut such heteroduplexes at the nonbase-paired region to produce fragments whose lengths correspond to the position of the deletion. Similarly, specific fragments are produced when S1 nuclease cleaves a heteroduplex formed from the DNAs of SV40 temperature-sensitive mutants and either their revertants or wild-type parents. Thus, the positions of the nonhomology between these DNAs can be determined.", "contents": "Biochemical method for mapping mutational alterations in DNA with S1 nuclease: the location of deletions and temperature-sensitive mutations in simian virus 40. S1 nuclease (EC 3.1.4.X), a single-strand-specific nuclease, can be used to accurately map the location of mutational alterations in simian virus 40 (SV40) DNA. Deletions of between 32 and 190 base pairs, which are at or below the limit of detectability by conventional electron microscopic analysis of heteroduplex DNAs, have been located in this way. To map a deletion, a mixture of unit length, linear DNA, prepared from the SV40 deletion mutant and its wild-type parent, are denatured and reannealed to form heteroduplexes. S1 nuclease can cut such heteroduplexes at the nonbase-paired region to produce fragments whose lengths correspond to the position of the deletion. Similarly, specific fragments are produced when S1 nuclease cleaves a heteroduplex formed from the DNAs of SV40 temperature-sensitive mutants and either their revertants or wild-type parents. Thus, the positions of the nonhomology between these DNAs can be determined."} {"id": "PMID:165499", "title": "Patterns of organization of actin and myosin in normal and transformed cultured cells.", "content": "The patterns of distribution of intracellular actin and myosin were examined by specific immunofluorescence in a series of normal, simian-virus-40-transformed, and revertant cell lines of rat and mouse origin. A consistent correlation was found between sensitivity to anchorage-dependent growth control and the presence of large, thick sheaths of actin-containing material. The presence of these sheaths was temperature-dependent in a rat line transformed by a temperature-sensitive mutant in the complementation group A of the oncogenic virus simian virus 40.", "contents": "Patterns of organization of actin and myosin in normal and transformed cultured cells. The patterns of distribution of intracellular actin and myosin were examined by specific immunofluorescence in a series of normal, simian-virus-40-transformed, and revertant cell lines of rat and mouse origin. A consistent correlation was found between sensitivity to anchorage-dependent growth control and the presence of large, thick sheaths of actin-containing material. The presence of these sheaths was temperature-dependent in a rat line transformed by a temperature-sensitive mutant in the complementation group A of the oncogenic virus simian virus 40."} {"id": "PMID:165500", "title": "Selective blockage of initiation of host protein synthesis in RNA-virus-infected cells.", "content": "Poliovirus mRNA and mRNA transcribed from vesicular stomatitis virus and reovirus genomes efficiently direct protein synthesis in vivo under experimental conditions where the initiation of host protein synthesis is selectively blocked. The selective blockage of host peptide chain initiation after exposure to hypertonic medium indicates that the translation of viral mRNA is more efficiently initiated than is the translation of host mRNA. It further suggests that virus directed suppression of host protein synthesis could proceed by a mechanism involving a nonspecific decrease in the rate of peptide chain initiation. Exposure of infected cells to hypertonic medium provides a unique tool with which to study early events in the infectious cycle by permitting the efficient unmasking of virus-specific poly-peptide synthesis.", "contents": "Selective blockage of initiation of host protein synthesis in RNA-virus-infected cells. Poliovirus mRNA and mRNA transcribed from vesicular stomatitis virus and reovirus genomes efficiently direct protein synthesis in vivo under experimental conditions where the initiation of host protein synthesis is selectively blocked. The selective blockage of host peptide chain initiation after exposure to hypertonic medium indicates that the translation of viral mRNA is more efficiently initiated than is the translation of host mRNA. It further suggests that virus directed suppression of host protein synthesis could proceed by a mechanism involving a nonspecific decrease in the rate of peptide chain initiation. Exposure of infected cells to hypertonic medium provides a unique tool with which to study early events in the infectious cycle by permitting the efficient unmasking of virus-specific poly-peptide synthesis."} {"id": "PMID:165501", "title": "Cyclic AMP modulates microvillus formation and agglutinability in transformed and normal mouse fibroblasts.", "content": "We have utilized dark field microscopy to observe the surface microstructure of living cultured cells. Using this method, we have found that dibutyryl cAMP treatment causes regression of the numerous, long cell surface microvilli present on L929 cells. Thirty minutes after removal of dibutyryl cAMP, microvilli reappear. An inhibitor of phosphodiesterase (methylisobutylxanthine) and a stimulator of adenylate cyclase (prostaglandin E1), both of which raise cAMP levels, cause regression of microvilli in 15 min. Untransformed 3T3 cells show very few microvilli when viewed still attached to their substratum or after removal with EDTA. Treatment of these cells with trypsin causes the formation of numerous microvilli on their surface. When clumps of cells agglutinated by concanavalin A are examined by thin section electron microscopy, the cells are seen to be held together by a \"forest\" of interdigitating microvilli and only rarely is there apposition of the areas of membrane between microvilli. At the same time the distribution of surface-bound concanavalin A was examined using immunofluorescent light microscopy, and concanavalin A was found to be uniformly distributed over the cell surface. We propose that agglutinability of mouse and rat fibroblasts is regulated through the modulation of cell surface microvilli by cAMP, and that transformed cells are highly agglutinable because their low cAMP levels result in the formation of numerous surface microvilli.", "contents": "Cyclic AMP modulates microvillus formation and agglutinability in transformed and normal mouse fibroblasts. We have utilized dark field microscopy to observe the surface microstructure of living cultured cells. Using this method, we have found that dibutyryl cAMP treatment causes regression of the numerous, long cell surface microvilli present on L929 cells. Thirty minutes after removal of dibutyryl cAMP, microvilli reappear. An inhibitor of phosphodiesterase (methylisobutylxanthine) and a stimulator of adenylate cyclase (prostaglandin E1), both of which raise cAMP levels, cause regression of microvilli in 15 min. Untransformed 3T3 cells show very few microvilli when viewed still attached to their substratum or after removal with EDTA. Treatment of these cells with trypsin causes the formation of numerous microvilli on their surface. When clumps of cells agglutinated by concanavalin A are examined by thin section electron microscopy, the cells are seen to be held together by a \"forest\" of interdigitating microvilli and only rarely is there apposition of the areas of membrane between microvilli. At the same time the distribution of surface-bound concanavalin A was examined using immunofluorescent light microscopy, and concanavalin A was found to be uniformly distributed over the cell surface. We propose that agglutinability of mouse and rat fibroblasts is regulated through the modulation of cell surface microvilli by cAMP, and that transformed cells are highly agglutinable because their low cAMP levels result in the formation of numerous surface microvilli."} {"id": "PMID:165502", "title": "Physical characteristics of the gonadotropin receptor-hormone complexes formed in vivo and in vitro.", "content": "The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo and in vitro labeling of specific ovarian binding sites with radioiodinated human chorionic gonadotropin (hCG). Following intravenous administration of biologically active 125I-labeled hCG, up to 50% of the gonadotropin tracer was bound to the luteinized ovaries of immature female rats treated with pregnant mare serum/human chorionic gonadotropin. Comparable binding of 125I-labeled hCG was observed after equilibration of ovarian particles with the labeled hormone in vitro. The sedimentation properties of the solubilized receptor-hormone complexes formed in vivo were identical with those derived for the corresponding complexes formed in vitro and extracted with Triton X-100 and Lubrol PX, with sedimentation constants of 8.8 S for the Triton-solubilized complex and 7.0 S for the complex extracted with Lubrol PX. During analytical gel filtration of the Triton-solubilized receptor-hormone complex on Sepharose 6B in 0.1% Triton X-100, the partition coefficient (Kav) of the \"in vivo\" complex (0.32) was not significantly different from that of the complex formed in vitro (0.29). Gel filtration of the Lubrol-solubilized ovarian particles on Sepharose 6B in 0.5% Lubrol PX gave Kav values for the \"in vivo\" and \"in vitro\" labeled complexes of 0.36 and 0.32, respectively. These findings demonstrate that the physical properties of size and shape which determine the partition coefficient and sedimentation characteristics of detergent-solubilized gonadotropin receptor-hormone complexes formed in vitro are not distinguishable from those of the complexes extracted after specific interaction of the ovarian gonadotropin receptors with radioiodinated hCG in vivo.", "contents": "Physical characteristics of the gonadotropin receptor-hormone complexes formed in vivo and in vitro. The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo and in vitro labeling of specific ovarian binding sites with radioiodinated human chorionic gonadotropin (hCG). Following intravenous administration of biologically active 125I-labeled hCG, up to 50% of the gonadotropin tracer was bound to the luteinized ovaries of immature female rats treated with pregnant mare serum/human chorionic gonadotropin. Comparable binding of 125I-labeled hCG was observed after equilibration of ovarian particles with the labeled hormone in vitro. The sedimentation properties of the solubilized receptor-hormone complexes formed in vivo were identical with those derived for the corresponding complexes formed in vitro and extracted with Triton X-100 and Lubrol PX, with sedimentation constants of 8.8 S for the Triton-solubilized complex and 7.0 S for the complex extracted with Lubrol PX. During analytical gel filtration of the Triton-solubilized receptor-hormone complex on Sepharose 6B in 0.1% Triton X-100, the partition coefficient (Kav) of the \"in vivo\" complex (0.32) was not significantly different from that of the complex formed in vitro (0.29). Gel filtration of the Lubrol-solubilized ovarian particles on Sepharose 6B in 0.5% Lubrol PX gave Kav values for the \"in vivo\" and \"in vitro\" labeled complexes of 0.36 and 0.32, respectively. These findings demonstrate that the physical properties of size and shape which determine the partition coefficient and sedimentation characteristics of detergent-solubilized gonadotropin receptor-hormone complexes formed in vitro are not distinguishable from those of the complexes extracted after specific interaction of the ovarian gonadotropin receptors with radioiodinated hCG in vivo."} {"id": "PMID:165503", "title": "Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides.", "content": "It was previously shown that virus-specific polypeptides made in HEp-2 cells infected with herpes simplex 1 form three groups designated alpha, beta, and gamma whose synthesis is coordinately regulated and sequentially ordered. This report shows that one or more functional alpha polypeptides are necessary to turn on the synthesis of beta and gamma groups, and conversely, one or more polypeptides in the latter groups turn off the synthesis of alpha polypeptides. Specifically, infected cells maintained in medium containing either canavanine, an analogue of arginine, or azetidine-2-carboxylic acid an analogue of proline and hydroxyproline, synthesized alpha polypeptide at rates comparable to maximal rates in untreated infected cells but did not undergo the normal transition to beta and gamma polypeptide synthesis. The transition to gamma polypeptide synthesis and shut-off of synthesis of earlier polypeptide groups proceeded normally if addition of canavanine was delayed until at least 4-5 hr after infection. Addition of canavanine after the onset of beta and gamma polypeptide synthesis, i.e., between 2 and 3.5 hr after infection, resulted in sustained, simultaneous synthesis of all three polypeptide groups, a phenomenon not seen in untreated infected cells. Canavanine-treated infected cells, synthesizing alpha polypeptides, recovered the capacity to make beta and gamma polypeptides after removal of the analogue, but only after a 1-to 2-hr delay compared with infected untreated cells. The data indicate that the on and off controls inherent in the cascade regulation of viral polypeptide synthesis are mediated by one or more polypeptides in each group at transcriptional or post-transcriptional levels.", "contents": "Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides. It was previously shown that virus-specific polypeptides made in HEp-2 cells infected with herpes simplex 1 form three groups designated alpha, beta, and gamma whose synthesis is coordinately regulated and sequentially ordered. This report shows that one or more functional alpha polypeptides are necessary to turn on the synthesis of beta and gamma groups, and conversely, one or more polypeptides in the latter groups turn off the synthesis of alpha polypeptides. Specifically, infected cells maintained in medium containing either canavanine, an analogue of arginine, or azetidine-2-carboxylic acid an analogue of proline and hydroxyproline, synthesized alpha polypeptide at rates comparable to maximal rates in untreated infected cells but did not undergo the normal transition to beta and gamma polypeptide synthesis. The transition to gamma polypeptide synthesis and shut-off of synthesis of earlier polypeptide groups proceeded normally if addition of canavanine was delayed until at least 4-5 hr after infection. Addition of canavanine after the onset of beta and gamma polypeptide synthesis, i.e., between 2 and 3.5 hr after infection, resulted in sustained, simultaneous synthesis of all three polypeptide groups, a phenomenon not seen in untreated infected cells. Canavanine-treated infected cells, synthesizing alpha polypeptides, recovered the capacity to make beta and gamma polypeptides after removal of the analogue, but only after a 1-to 2-hr delay compared with infected untreated cells. The data indicate that the on and off controls inherent in the cascade regulation of viral polypeptide synthesis are mediated by one or more polypeptides in each group at transcriptional or post-transcriptional levels."} {"id": "PMID:165504", "title": "Tumor-inhibiting properties of the neutral P-O-ethyl ester of adenosine 3':5'-monophosphate in correlation with its crystal and molecular structure.", "content": "The P-O-ethyl ester of cAMP has been synthesized, its inhibition of solid and ascites tumors studied, and its pattern of urinary excretion followed. Et-cAMP is more effective than cAMP against solid sarcoma 180 in mice and against Ehrlich ascites carcinoma cells in tissue culture. The urinary excretion pattern of injected E-t-cAMP suggests that about two-thirds of the injected dose (13 mumol per animal) is retained in the rat rather than being promptly excreted. Liver slice studies of the effect on glycogenolysis suggest that the Et-cAMP is converted to cAMP intracellularly. The compound crystallizes in space group P21 with one molecule per asymmetric unit. The base ring has the anti conformation. The ethyl group is endo to the base ring and is axial in the flattened chair-conformer six-membered ring formed by the 3'-5' O-P-O cyclization. In most other respects the structure of the compound is closely similar to the known structures of other cyclic nucleotides.", "contents": "Tumor-inhibiting properties of the neutral P-O-ethyl ester of adenosine 3':5'-monophosphate in correlation with its crystal and molecular structure. The P-O-ethyl ester of cAMP has been synthesized, its inhibition of solid and ascites tumors studied, and its pattern of urinary excretion followed. Et-cAMP is more effective than cAMP against solid sarcoma 180 in mice and against Ehrlich ascites carcinoma cells in tissue culture. The urinary excretion pattern of injected E-t-cAMP suggests that about two-thirds of the injected dose (13 mumol per animal) is retained in the rat rather than being promptly excreted. Liver slice studies of the effect on glycogenolysis suggest that the Et-cAMP is converted to cAMP intracellularly. The compound crystallizes in space group P21 with one molecule per asymmetric unit. The base ring has the anti conformation. The ethyl group is endo to the base ring and is axial in the flattened chair-conformer six-membered ring formed by the 3'-5' O-P-O cyclization. In most other respects the structure of the compound is closely similar to the known structures of other cyclic nucleotides."} {"id": "PMID:165505", "title": "Biochemical procedure for production of small deletions in simian virus 40 DNA.", "content": "A simple biochemical procedure for producing small deletions (15 to 50 base pairs) at virtually any location in simian virus 40 DNA has been developed. The steps involved are: cleavage of the closed-circular DNA to produce a linear structure followed by 5'-exonuclease digestion to expose a short single-stranded segment at each 3' end of the molecule. Mutants containing deletions at the site of the cleavage are obtained by infecting permissive monkey kidney cells with the exonuclease-treated DNA in the presence or absence of a helper DNA (depending upon whether or not the site of cleavage and therefore the deletion occurred in a gene required for vegetative multiplication). In this paper viable mutants with deletions at the HpaII endonuclease cleavage site (0.735 map position) and defective trans-complementable mutants with deletions at the EcoRI endonuclease cleavage site (0/1.0 map position) were isolated.", "contents": "Biochemical procedure for production of small deletions in simian virus 40 DNA. A simple biochemical procedure for producing small deletions (15 to 50 base pairs) at virtually any location in simian virus 40 DNA has been developed. The steps involved are: cleavage of the closed-circular DNA to produce a linear structure followed by 5'-exonuclease digestion to expose a short single-stranded segment at each 3' end of the molecule. Mutants containing deletions at the site of the cleavage are obtained by infecting permissive monkey kidney cells with the exonuclease-treated DNA in the presence or absence of a helper DNA (depending upon whether or not the site of cleavage and therefore the deletion occurred in a gene required for vegetative multiplication). In this paper viable mutants with deletions at the HpaII endonuclease cleavage site (0.735 map position) and defective trans-complementable mutants with deletions at the EcoRI endonuclease cleavage site (0/1.0 map position) were isolated."} {"id": "PMID:165506", "title": "Somatic cell hybrids between mouse peritoneal macrophages and simian-virus-40-transformed human cells: II. Presence of human chromosome 7 carrying simin virus 40 genome in cells of tumors induced by hybrid cells.", "content": "Cells derived from tumors induced in \"nude\" mice after injection of cells that were hybrids between mouse peritoneal macrophages and simian virus 40 (SV40)-transformed human cells were found to retain the human chromosome 7 carrying the SV40 genome, and indicate that the presence of human chromosome 7 carrying the SV40 genome is responsible for the expression of the tumorigenic phenotype in the hybrid cells.", "contents": "Somatic cell hybrids between mouse peritoneal macrophages and simian-virus-40-transformed human cells: II. Presence of human chromosome 7 carrying simin virus 40 genome in cells of tumors induced by hybrid cells. Cells derived from tumors induced in \"nude\" mice after injection of cells that were hybrids between mouse peritoneal macrophages and simian virus 40 (SV40)-transformed human cells were found to retain the human chromosome 7 carrying the SV40 genome, and indicate that the presence of human chromosome 7 carrying the SV40 genome is responsible for the expression of the tumorigenic phenotype in the hybrid cells."} {"id": "PMID:165507", "title": "Estrogen-directed synthesis of specific prostaglandins in uterus.", "content": "Endogenous uterine prostaglandin levels were monitored in the cycling rat and prostaglandins of the F-type were found to rise at proestrus when estrogen levels have been shown to be maximal. Evidence that this is an estrogen-induced event is furnished by the finding that estradiol-17beta caused a similar rise in prostaglandin F levels in uteri of ovariectomized rats, an action blocked by coadministration of progesterone. Examination of in vitro prostaglandin synthetase by uterine microsomal fractions from cycling rats and estrogen-treated ovariectomized rats revealed that the action of estrogen to control prostaglandin synthesis in a directional manner is accomplished, at least in part, by regulation of the prostaglandin synthetase complex, resulting in a patterned alteration in the ratio of prostaglandin F to prostaglandin E. These results demonstrate that prostaglandins are involved in the expression of estrogen action in the rat uterus.", "contents": "Estrogen-directed synthesis of specific prostaglandins in uterus. Endogenous uterine prostaglandin levels were monitored in the cycling rat and prostaglandins of the F-type were found to rise at proestrus when estrogen levels have been shown to be maximal. Evidence that this is an estrogen-induced event is furnished by the finding that estradiol-17beta caused a similar rise in prostaglandin F levels in uteri of ovariectomized rats, an action blocked by coadministration of progesterone. Examination of in vitro prostaglandin synthetase by uterine microsomal fractions from cycling rats and estrogen-treated ovariectomized rats revealed that the action of estrogen to control prostaglandin synthesis in a directional manner is accomplished, at least in part, by regulation of the prostaglandin synthetase complex, resulting in a patterned alteration in the ratio of prostaglandin F to prostaglandin E. These results demonstrate that prostaglandins are involved in the expression of estrogen action in the rat uterus."} {"id": "PMID:165508", "title": "Macromolecular enzymatic product of NAD+ in liver mitochondria.", "content": "Rat liver mitochondria contain a Mg2+-requiring system that transfers the ADP-ribose moiety of NAD+ to an acceptor protein. The enzyme system was extracted in a soluble form and the ADP-ribosylated protein product was isolated by hydroxyapatite and Sephadex chromatography. The ADP-ribosylated protein product has a molecular weight of 100,000 and can be dissociated into subunits of 50,000 daltons by sodium dodecyl sulfate gel electrophoresis. Incubation of the isotopically labeled ADP-ribosylated protein with nicotinamide and a mitochondrial extract yields labeled NAD+, indicating apparent reversibility of the reaction. Enzymatic degradation of the ADP-ribosylated protein with snake venom phosphodiesterase liberates AMP and ADP-ribose or its isomer. Identification of these products and reversibility of the reaction show that the ADP-ribose moiety of NAD+ is the molecular species that is transferred to the acceptor protein. A fraction of the protein-bound ADP-ribose appears to be present as an an oligomer. The enzymatic protein-ADP-ribosylating reaction is inhibited by nicotinamide, ADP-ribose, the fluorophosphate of AMP, and picrylsulfonic acid.", "contents": "Macromolecular enzymatic product of NAD+ in liver mitochondria. Rat liver mitochondria contain a Mg2+-requiring system that transfers the ADP-ribose moiety of NAD+ to an acceptor protein. The enzyme system was extracted in a soluble form and the ADP-ribosylated protein product was isolated by hydroxyapatite and Sephadex chromatography. The ADP-ribosylated protein product has a molecular weight of 100,000 and can be dissociated into subunits of 50,000 daltons by sodium dodecyl sulfate gel electrophoresis. Incubation of the isotopically labeled ADP-ribosylated protein with nicotinamide and a mitochondrial extract yields labeled NAD+, indicating apparent reversibility of the reaction. Enzymatic degradation of the ADP-ribosylated protein with snake venom phosphodiesterase liberates AMP and ADP-ribose or its isomer. Identification of these products and reversibility of the reaction show that the ADP-ribose moiety of NAD+ is the molecular species that is transferred to the acceptor protein. A fraction of the protein-bound ADP-ribose appears to be present as an an oligomer. The enzymatic protein-ADP-ribosylating reaction is inhibited by nicotinamide, ADP-ribose, the fluorophosphate of AMP, and picrylsulfonic acid."} {"id": "PMID:165509", "title": "Magnetic resonance spectra of membranes.", "content": "A number of electron and nuclear magnetic resonance studies of model membranes, and biological membranes, involve time-dependent magnetic interactions diffusion relative to one another. The two-dimensional character of this motion can have a special, large effect on magnetic resonance line shapes, and relaxation rates, because of the long-time tail of the correlation function for magnetic interactions modulated by this motion. Equations are given for the specific case in which nuclear relaxation rates are enhanced due to dipolar interactions with membrane-bound spin labels. An experimental study of spin-label-enhanced 13-C nuclear relaxation in unsonicated dispersions of phosphatidylcholine is accounted for with this theory, together with the previously reported lipid diffusion constant of D congruent to 2 times 10- minus 8 cm-2/sec. Our analysis of previously reported 1-H and 13-C nuclear relaxation rates in small phospholipid vesicles produced by sonication suggests that the rate of lateral diffusion in these small vesicles may be significantly larger than 10- minus 8 cm-2/sec.", "contents": "Magnetic resonance spectra of membranes. A number of electron and nuclear magnetic resonance studies of model membranes, and biological membranes, involve time-dependent magnetic interactions diffusion relative to one another. The two-dimensional character of this motion can have a special, large effect on magnetic resonance line shapes, and relaxation rates, because of the long-time tail of the correlation function for magnetic interactions modulated by this motion. Equations are given for the specific case in which nuclear relaxation rates are enhanced due to dipolar interactions with membrane-bound spin labels. An experimental study of spin-label-enhanced 13-C nuclear relaxation in unsonicated dispersions of phosphatidylcholine is accounted for with this theory, together with the previously reported lipid diffusion constant of D congruent to 2 times 10- minus 8 cm-2/sec. Our analysis of previously reported 1-H and 13-C nuclear relaxation rates in small phospholipid vesicles produced by sonication suggests that the rate of lateral diffusion in these small vesicles may be significantly larger than 10- minus 8 cm-2/sec."} {"id": "PMID:165510", "title": "Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity.", "content": "We have studied androgen binding characteristics of cells for androgen insensitivity from an obligate heterozygote, who is the mother of three male pseudohermaphrodites with dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) receptor deficiency. Specific dihydrotestosterone binding by skin fibroblasts from her wrist and pubis is within the normal range and indicates that androgen insensitivity is X-linked in man and is therefore homologous to the tfm locus in the mouse. A significant population of clones from the heterozygote has deficient receptor activity, and this finding is compatible with inactivation of one X-linked allele at this locus. Our results indicate the presence of a gene on the human X chromosome that is essential for normal male sexual differentiation and provide further evidence for homology between X chromosomes of all mammals.", "contents": "Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity. We have studied androgen binding characteristics of cells for androgen insensitivity from an obligate heterozygote, who is the mother of three male pseudohermaphrodites with dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) receptor deficiency. Specific dihydrotestosterone binding by skin fibroblasts from her wrist and pubis is within the normal range and indicates that androgen insensitivity is X-linked in man and is therefore homologous to the tfm locus in the mouse. A significant population of clones from the heterozygote has deficient receptor activity, and this finding is compatible with inactivation of one X-linked allele at this locus. Our results indicate the presence of a gene on the human X chromosome that is essential for normal male sexual differentiation and provide further evidence for homology between X chromosomes of all mammals."} {"id": "PMID:165511", "title": "Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells.", "content": "A high-density fraction of high-molecular-weight DNA was isolated from the human lymphoid cell line Raji. This cell line contains 50 to 60 virus genome equivalents of Epstein-Barr virus DNA per cell, and the high-density DNA fraction was 10-fold enriched in such viral sequences. Sedimentation analysis on neutral glycerol gradients, followed by hybridization experiments with viral complementary RNA, showed that most of the intracellular viral DNA sequences in this material did not cosediment with the cellular DNA, but were recovered as two distinct species with sedimentation coefficients of 100 S and 65 S. These two forms sediment 1.70-1.75 and 1.10-1.12 times as fast as the linear Epstein-Barr virus DNA from virus particles, and thus have the hydrodynamic properties of a covalently closed circular form and a nicked (containing single-strand breaks) circular form of the virus genome. The 100S form also behaved as a covalently closed circular EBV DNA molecule on gradient centrifugation in CsC1/propidium diiodide, It would appear that latent Epstein-Barr virus DNA has the properties of a mammalian episome, and that both nonintegrated and integrated viral DNA sequences can be isolated from carrier cells.", "contents": "Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. A high-density fraction of high-molecular-weight DNA was isolated from the human lymphoid cell line Raji. This cell line contains 50 to 60 virus genome equivalents of Epstein-Barr virus DNA per cell, and the high-density DNA fraction was 10-fold enriched in such viral sequences. Sedimentation analysis on neutral glycerol gradients, followed by hybridization experiments with viral complementary RNA, showed that most of the intracellular viral DNA sequences in this material did not cosediment with the cellular DNA, but were recovered as two distinct species with sedimentation coefficients of 100 S and 65 S. These two forms sediment 1.70-1.75 and 1.10-1.12 times as fast as the linear Epstein-Barr virus DNA from virus particles, and thus have the hydrodynamic properties of a covalently closed circular form and a nicked (containing single-strand breaks) circular form of the virus genome. The 100S form also behaved as a covalently closed circular EBV DNA molecule on gradient centrifugation in CsC1/propidium diiodide, It would appear that latent Epstein-Barr virus DNA has the properties of a mammalian episome, and that both nonintegrated and integrated viral DNA sequences can be isolated from carrier cells."} {"id": "PMID:165512", "title": "Cell cycle specific fluctuations in adenosine 3':5'-cyclic monophosphate and polyamines of Chinese hamster cells.", "content": "Chinese hamster V79 cells were synchronized by mitotic selection, which resulted in approximately 95% synchrony. The adenosine 3':5'-cyclic monophosphate level was elevated within 3 hr (G1 phase) and reached a level 2-fold higher than in early G1 within 6 hr (early S phase). An increase in ornithine decarboxylase activity (6-ornithine carboxy-lyase, EC 4.1.1.17), the initial enzyme in the polyamine biosynthetic pathway, was detected within 4 hr and was maximal at 8 hr. Since about 20% of the cells were labeled with [3-H]thymidine at 4 hr, ornithine decarboxylase exhibits cell-cycle specific activity starting in late G1 and continuing through middle S phase. The activity of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxylase, EC 4.1.1.50) increased within 5 hr, i.e., early S phase. It is suggested on the basis of these data and other studies discussed herein that the increase in ornithine decarboxylase activity, which parallels closely the elevation in cyclic AMP, is an example of adenosine 3':5'-cyclic monophosphate-mediated protein synthesis.", "contents": "Cell cycle specific fluctuations in adenosine 3':5'-cyclic monophosphate and polyamines of Chinese hamster cells. Chinese hamster V79 cells were synchronized by mitotic selection, which resulted in approximately 95% synchrony. The adenosine 3':5'-cyclic monophosphate level was elevated within 3 hr (G1 phase) and reached a level 2-fold higher than in early G1 within 6 hr (early S phase). An increase in ornithine decarboxylase activity (6-ornithine carboxy-lyase, EC 4.1.1.17), the initial enzyme in the polyamine biosynthetic pathway, was detected within 4 hr and was maximal at 8 hr. Since about 20% of the cells were labeled with [3-H]thymidine at 4 hr, ornithine decarboxylase exhibits cell-cycle specific activity starting in late G1 and continuing through middle S phase. The activity of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxylase, EC 4.1.1.50) increased within 5 hr, i.e., early S phase. It is suggested on the basis of these data and other studies discussed herein that the increase in ornithine decarboxylase activity, which parallels closely the elevation in cyclic AMP, is an example of adenosine 3':5'-cyclic monophosphate-mediated protein synthesis."} {"id": "PMID:165513", "title": "On the question of translocation of heart cAMP-dependent protein kinase.", "content": "Rat hearts were perfused with epinephrine and/or 1-methyl-3-isobutylxanthine for 2 min. These agents raised the concentration of cAMP and increased the fraction of cAMP-dependent protein kinase (EC 2.7.1.70) in the active form. However, the content of cAMP-dependent protein kinase in the soluble fraction of homogenates of these hearts was reduced and the amount in the particulate fraction was increased. A similar redistribution was obtained by adding cAMP to homogenates of control hearts. The reduction in soluble protein kinase content was due to apparent binding of the free catalytic subunit of the enzyme to particulate material (12,000 times g pellet) in media of low ionic strength (smaller than 100 mM KCl). The amount bound was, therefore, proportional to the dissociation of the holoenzyme. The binding was not altered by prior boiling or trypsin treatment of the particulate material, but it was prevented or reversed by the addition of 150 mM KCl. The catalytic subunit of the protein kinase from heart also bound to particulate fractions from liver or Escherichia coli and to various denatured proteins. These findings suggest that the protein kinase activity of membranes and particulate fractions has frequently been overestimated, since isolation of particulate materials has usually been carried out at low ionic strength. The data also imply that intracellular translocation of the protein kinase catalytic subunit, at least in heart tissue, is of questionable physiological significance.", "contents": "On the question of translocation of heart cAMP-dependent protein kinase. Rat hearts were perfused with epinephrine and/or 1-methyl-3-isobutylxanthine for 2 min. These agents raised the concentration of cAMP and increased the fraction of cAMP-dependent protein kinase (EC 2.7.1.70) in the active form. However, the content of cAMP-dependent protein kinase in the soluble fraction of homogenates of these hearts was reduced and the amount in the particulate fraction was increased. A similar redistribution was obtained by adding cAMP to homogenates of control hearts. The reduction in soluble protein kinase content was due to apparent binding of the free catalytic subunit of the enzyme to particulate material (12,000 times g pellet) in media of low ionic strength (smaller than 100 mM KCl). The amount bound was, therefore, proportional to the dissociation of the holoenzyme. The binding was not altered by prior boiling or trypsin treatment of the particulate material, but it was prevented or reversed by the addition of 150 mM KCl. The catalytic subunit of the protein kinase from heart also bound to particulate fractions from liver or Escherichia coli and to various denatured proteins. These findings suggest that the protein kinase activity of membranes and particulate fractions has frequently been overestimated, since isolation of particulate materials has usually been carried out at low ionic strength. The data also imply that intracellular translocation of the protein kinase catalytic subunit, at least in heart tissue, is of questionable physiological significance."} {"id": "PMID:165514", "title": "RNA of replication-defective strains of Rous sarcoma virus.", "content": "The RNA of a replication-defective (rd) mutant, isolated from stocks of nondefective (nd) Schmidt-Ruppin Rous sarcoma virus of subgroup A (SR-A) and termed SR-N8, was compared to the RNAs of SR-A, of a transformation-defective derivative of SR-A (td SR-A) and of rd Bryan Rous sarcoma virus, RSV (minus). The molecular mass of the 30-40S species of SR-N8 RNA was estimated to be 21% (congruent to 7.5 to 8 times 10-5 daltons) smaller than that of SR-A by (i) electrophoresis in polyacrylamide gels and (ii) analyses of RNA complexity based on RNase T1-resistant oligonucleotides. ST-N8 shares probably all (=14) of its large RNase T1-resistant oligonucleotides with the RNA of SR-A as judged from the chromatographic distribution and the RNase A-resistant fragments obtained from RNase T1-resistant oligonucleotides. However, SR-N8 RNA lacked six large oligonucleotides which were present in the RNAs of SR-A and td SR-A. Conversely, the RNAs of SR-A, and of SR-N8 contained two oligonucleotides not found in td SR-A. The RNA of SR-N8 was found to differ from that of RSV (minus) in its electrophoretic mobility and its fingerprint pattern. It is concluded that the RNA of SR-N8 was generated by a deletion of SR-A. The extent of this deletion is compatible with the notion that the genetic information for the large viral envelope glycoprotein (molecular mass = 70,000-85,000 daltons) has been lost from the RNA of SR-A to yield SR-N8 RNA. From a comparison of td and rd deletion mutants, it appears that loss of different functions corresponds to the absence of different oligonucleotides in their RNA.", "contents": "RNA of replication-defective strains of Rous sarcoma virus. The RNA of a replication-defective (rd) mutant, isolated from stocks of nondefective (nd) Schmidt-Ruppin Rous sarcoma virus of subgroup A (SR-A) and termed SR-N8, was compared to the RNAs of SR-A, of a transformation-defective derivative of SR-A (td SR-A) and of rd Bryan Rous sarcoma virus, RSV (minus). The molecular mass of the 30-40S species of SR-N8 RNA was estimated to be 21% (congruent to 7.5 to 8 times 10-5 daltons) smaller than that of SR-A by (i) electrophoresis in polyacrylamide gels and (ii) analyses of RNA complexity based on RNase T1-resistant oligonucleotides. ST-N8 shares probably all (=14) of its large RNase T1-resistant oligonucleotides with the RNA of SR-A as judged from the chromatographic distribution and the RNase A-resistant fragments obtained from RNase T1-resistant oligonucleotides. However, SR-N8 RNA lacked six large oligonucleotides which were present in the RNAs of SR-A and td SR-A. Conversely, the RNAs of SR-A, and of SR-N8 contained two oligonucleotides not found in td SR-A. The RNA of SR-N8 was found to differ from that of RSV (minus) in its electrophoretic mobility and its fingerprint pattern. It is concluded that the RNA of SR-N8 was generated by a deletion of SR-A. The extent of this deletion is compatible with the notion that the genetic information for the large viral envelope glycoprotein (molecular mass = 70,000-85,000 daltons) has been lost from the RNA of SR-A to yield SR-N8 RNA. From a comparison of td and rd deletion mutants, it appears that loss of different functions corresponds to the absence of different oligonucleotides in their RNA."} {"id": "PMID:165515", "title": "Induction of growth in resting fibroblastic cell cultures by Ca++.", "content": "Of all the components of the culture medium, only CaCl2 induces DNA replication when added to resting cultures of Balb/c 3T3 cells. The effect is present even in a serum-free medium. Increasing the Ca++ concentration above the standard 1.8 mM in the medium of a new culture increases the total number of cells ultimately produced, without affecting the initial cell growth rate. This effect is synergistic with that of serum. The elevated Ca++ concentration also induces striking morphological changes. The Ca++ effect could not be reproduced by a Ca++ ionophore. These observations afford a new tool for studying how the various intracellular events following the addition of growth factors to resting cultures are involved in the control of cellular growth.", "contents": "Induction of growth in resting fibroblastic cell cultures by Ca++. Of all the components of the culture medium, only CaCl2 induces DNA replication when added to resting cultures of Balb/c 3T3 cells. The effect is present even in a serum-free medium. Increasing the Ca++ concentration above the standard 1.8 mM in the medium of a new culture increases the total number of cells ultimately produced, without affecting the initial cell growth rate. This effect is synergistic with that of serum. The elevated Ca++ concentration also induces striking morphological changes. The Ca++ effect could not be reproduced by a Ca++ ionophore. These observations afford a new tool for studying how the various intracellular events following the addition of growth factors to resting cultures are involved in the control of cellular growth."} {"id": "PMID:165516", "title": "Nuclear magnetic resonance spectroscopy: reinvestigation of carbon-13 spin-lattice relaxation time measurements of amino acids.", "content": "The carbon-13 spin-lattice relaxation times (T1) of glycine have been measured as a function of pD and concentration. Contrary to previously reported findings, no significant dependence was observed on either pD or concentration. In addition, the T1 values reported here are much longer than those published earlier. The discrepancies arise from the presence of paramagnetic impurities in the earlier samples. For the carboxyl carbon, dipole-dipole relaxation is dominant in both D2O and H2O solution, and in H2O there is a significant intermolecular dipolar contribution. Proton and oxygen relaxation times have also been measured. These, along with the carbon relaxation data, allow a discussion of the dynamics of glycine in solution.", "contents": "Nuclear magnetic resonance spectroscopy: reinvestigation of carbon-13 spin-lattice relaxation time measurements of amino acids. The carbon-13 spin-lattice relaxation times (T1) of glycine have been measured as a function of pD and concentration. Contrary to previously reported findings, no significant dependence was observed on either pD or concentration. In addition, the T1 values reported here are much longer than those published earlier. The discrepancies arise from the presence of paramagnetic impurities in the earlier samples. For the carboxyl carbon, dipole-dipole relaxation is dominant in both D2O and H2O solution, and in H2O there is a significant intermolecular dipolar contribution. Proton and oxygen relaxation times have also been measured. These, along with the carbon relaxation data, allow a discussion of the dynamics of glycine in solution."} {"id": "PMID:165517", "title": "T antigen binds to simian virus 40 DNA at the origin of replication.", "content": "A technique employing ferritin-conjugated antibody has been developed to visualize specific protein-DNA complexes in the electron microscope and has been used to demonstrate the preferential binding of simian virus 40 (SV40) T antigen at or near the origin of replication of SV40 DNA, 0.67 fractional length clockwise from the EcoRI restriction endonuclease cleavage site. urified covalently closed supercoiled circles of SV40DNA were treated with partially purified T antigen and the complex was stabilized by crosslinking with glutaraldehyde. Hamster antiT antigen gamma-globulin, ferritin-labeled goat anti-hamster gamma-globulin, and glutaraldehyde were then added sequentially. The location of the bound ferritin cores was measured with respect to the EcoRI cleavage site and the orientation of the cores relative to the ends of the DNA was determined with respect to the locations of Escherichia coli DNA unwinding protein, which binds to covalently closed supercoiled SV40 DNA at either of two preferred sites, 0.46 or 0.90 fractional length clockwide from the EcoRI cleavage site.", "contents": "T antigen binds to simian virus 40 DNA at the origin of replication. A technique employing ferritin-conjugated antibody has been developed to visualize specific protein-DNA complexes in the electron microscope and has been used to demonstrate the preferential binding of simian virus 40 (SV40) T antigen at or near the origin of replication of SV40 DNA, 0.67 fractional length clockwise from the EcoRI restriction endonuclease cleavage site. urified covalently closed supercoiled circles of SV40DNA were treated with partially purified T antigen and the complex was stabilized by crosslinking with glutaraldehyde. Hamster antiT antigen gamma-globulin, ferritin-labeled goat anti-hamster gamma-globulin, and glutaraldehyde were then added sequentially. The location of the bound ferritin cores was measured with respect to the EcoRI cleavage site and the orientation of the cores relative to the ends of the DNA was determined with respect to the locations of Escherichia coli DNA unwinding protein, which binds to covalently closed supercoiled SV40 DNA at either of two preferred sites, 0.46 or 0.90 fractional length clockwide from the EcoRI cleavage site."} {"id": "PMID:165518", "title": "Cytotoxic effector cells specific for B Cell lines transformed by Epstein-Barr virus are present in patients with infectious mononucleosis.", "content": "Peripheral lymphoid cells, from 12 cases of acute infectious mononucleosis (IM), were tested in a micro chromium-51 release assay for cytotoxic activity against a variety of cell lines that did or did not carry the Epstein-Barr virus (EBV) genome. Unfractionated lymphocytes from these patients were cytotoxic to both types of cell lines, as were lymphocytes from healthy individuals. If, however, lymphocytes bearing complement receptors were removed, the residual IM lymphocyte fraction was specifically cytotoxic for EBV-genome-carrying cell lines. The residual lymphocyte fraction in normal donors had no such effect. Heterophile-positive IM is caused by EBV, and these results indicate that, during the acute phase of this disease, patients harbor killer cells, probably T cells, which specifically kill EBV-genome-carrying B cells in vitro. No such specificity for EBV-genome-psitive target cells was found in normal lymphocytes stimulated in vitro with autologous EBV-genome-positive lymphoblastoid cells. Such stimulated cells were highly cytotoxic to both genome-positive and negative lines after removal of complement receptor-positive lymphocytes.", "contents": "Cytotoxic effector cells specific for B Cell lines transformed by Epstein-Barr virus are present in patients with infectious mononucleosis. Peripheral lymphoid cells, from 12 cases of acute infectious mononucleosis (IM), were tested in a micro chromium-51 release assay for cytotoxic activity against a variety of cell lines that did or did not carry the Epstein-Barr virus (EBV) genome. Unfractionated lymphocytes from these patients were cytotoxic to both types of cell lines, as were lymphocytes from healthy individuals. If, however, lymphocytes bearing complement receptors were removed, the residual IM lymphocyte fraction was specifically cytotoxic for EBV-genome-carrying cell lines. The residual lymphocyte fraction in normal donors had no such effect. Heterophile-positive IM is caused by EBV, and these results indicate that, during the acute phase of this disease, patients harbor killer cells, probably T cells, which specifically kill EBV-genome-carrying B cells in vitro. No such specificity for EBV-genome-psitive target cells was found in normal lymphocytes stimulated in vitro with autologous EBV-genome-positive lymphoblastoid cells. Such stimulated cells were highly cytotoxic to both genome-positive and negative lines after removal of complement receptor-positive lymphocytes."} {"id": "PMID:165519", "title": "Functional intermediates in reaction of cytochrome oxidase with oxygen.", "content": "The development of a low temperature kinetic method for the flash photolysis of the compounds of membrane-bound cytochrome a3 with carbon monoxide in the presence of oxygen affords evidence for three categories of functional intermediate compounds of cytochrome a3 and oxygen. The three classes are identified as follows: Compounds of Type A are considered to be \"oxy\" compounds of the ferrous heme. They have the composition a3-2+. O2. Compounds of Type B are considered to be peroxide compounds (CU-2+A3-3+ O-2= or CU-2+A3-3+ O2H2) or the equivalent heme Fe-Cu peroxide bridge structures. Compounds of Type C are formed from the ferricyanide pretreated oxidase and may involve higher oxidation states of the heme iron such as quadrivalent iron, and peroxide. Kinetic and equilibrium studies show these compounds to be functional in oxygen reduction in the sequence A yields B yield cytochromes a, c, c1, etc.", "contents": "Functional intermediates in reaction of cytochrome oxidase with oxygen. The development of a low temperature kinetic method for the flash photolysis of the compounds of membrane-bound cytochrome a3 with carbon monoxide in the presence of oxygen affords evidence for three categories of functional intermediate compounds of cytochrome a3 and oxygen. The three classes are identified as follows: Compounds of Type A are considered to be \"oxy\" compounds of the ferrous heme. They have the composition a3-2+. O2. Compounds of Type B are considered to be peroxide compounds (CU-2+A3-3+ O-2= or CU-2+A3-3+ O2H2) or the equivalent heme Fe-Cu peroxide bridge structures. Compounds of Type C are formed from the ferricyanide pretreated oxidase and may involve higher oxidation states of the heme iron such as quadrivalent iron, and peroxide. Kinetic and equilibrium studies show these compounds to be functional in oxygen reduction in the sequence A yields B yield cytochromes a, c, c1, etc."} {"id": "PMID:165520", "title": "Biologic and antigenic similarity of virus-induced migration inhibition factor to conventional, lymphocyte-derived migration inhibition factor.", "content": "Macrophage migration inhibition factor (MIF) is one of a class of lymphocyte-derived mediator substances (lymphokines) which plays a role in the mechanism of cellular immunity. A variety of other soluble factors produced by non-lymphoid cells have been shown to have effects on macrophage mobility similar to that of MIF. In the present study we demonstrate that one such factor, (MIFV) derived from simian virus 40-infected kidney cells in culture, has several other properties in common with lymphocyte-derived MIF (MIFL), MIFV can be adsorbed on Sepharose bead columns conjugated with an antiserum prepared against MIFL, demonstrating at least some antigenic similarity. Moreover, MIFV can substitute for MIFL in an in vivo system involving the suppression of cutaneous manifestations of cellular immunity by intravenous injection of the lymphokine. These observations, taken in conjunction with the similarity of the in vitro effect of MIFV and MIFL, and their similar chromatographic behavior, suggest that MIFV and MIFL may be identical molecular species.", "contents": "Biologic and antigenic similarity of virus-induced migration inhibition factor to conventional, lymphocyte-derived migration inhibition factor. Macrophage migration inhibition factor (MIF) is one of a class of lymphocyte-derived mediator substances (lymphokines) which plays a role in the mechanism of cellular immunity. A variety of other soluble factors produced by non-lymphoid cells have been shown to have effects on macrophage mobility similar to that of MIF. In the present study we demonstrate that one such factor, (MIFV) derived from simian virus 40-infected kidney cells in culture, has several other properties in common with lymphocyte-derived MIF (MIFL), MIFV can be adsorbed on Sepharose bead columns conjugated with an antiserum prepared against MIFL, demonstrating at least some antigenic similarity. Moreover, MIFV can substitute for MIFL in an in vivo system involving the suppression of cutaneous manifestations of cellular immunity by intravenous injection of the lymphokine. These observations, taken in conjunction with the similarity of the in vitro effect of MIFV and MIFL, and their similar chromatographic behavior, suggest that MIFV and MIFL may be identical molecular species."} {"id": "PMID:165521", "title": "Adrenal Cortical Ribonuclease H (hybrid) (38494).", "content": "Ribonuclease Hybrid (RNaseH) from adrenal cortical tissue has been characterized. RNase H specifically degrades the RNA strand of purified RNA:DNA hybrids but is inactive on single- or double-stranded RNA or on DNA. The mode of clevage by RNase H is endonucleolytic, producing oligoribonucleoties with 3'-hydroxyl and 5'- phosphate termini. ACTH administration to guinea pigs results in no detectable change in adrenal cortical RNase H activity at times when changes in DNA synthesis are marked.", "contents": "Adrenal Cortical Ribonuclease H (hybrid) (38494). Ribonuclease Hybrid (RNaseH) from adrenal cortical tissue has been characterized. RNase H specifically degrades the RNA strand of purified RNA:DNA hybrids but is inactive on single- or double-stranded RNA or on DNA. The mode of clevage by RNase H is endonucleolytic, producing oligoribonucleoties with 3'-hydroxyl and 5'- phosphate termini. ACTH administration to guinea pigs results in no detectable change in adrenal cortical RNase H activity at times when changes in DNA synthesis are marked."} {"id": "PMID:165522", "title": "Elevated cyclic AMP levels in mouse lymphoid tissue after stimulation by cholera enterotoxin in vitro (38468)", "content": "Addition of CT to suspensions of thymus, lymph node, spleen, or bone marrow cells in vitro resulted in a marked accumulation of cAMP with peak levels occurring 4-5 hr after incubation of cells with CT. Thymus cells showed the largest increase in cAMP, approximately 40-fold at 10 ng/ml CT. Bone marrow cells accumulated the least cAMP (1.5x), while intermediate levels were observed for spleen and lymph node cells (10-12x). Antiserum to CT prevented stimulation of increased cAMP levels. Repopulation studies using X-irradiated mice also showed that thymus-derived spleen cells accumulated more cAMP/10-7 cells than spleen cells from recipients given spleen or marrow cells. Spleen cells from athymic (nu/nu) mice also responded much less than did spleen cells from normal mice. Thymocytes appeared to bind CT to a greater degree than bone marrow cells. Spleen and lymph node cell suspensions also contained CT-binding cells and the number of CT-binding cells in these peripheral lymphoid tissues appeared approximately equal to the summation of the numbers observed in thymocyte and bone marrow cell suspensions. Stimulation of cAMP in lymphoid cells, especially thymocytes, by CT provides a pharmacological tool to investigate the mechanism and role of this nucleotide in the early events of antibody formation.", "contents": "Elevated cyclic AMP levels in mouse lymphoid tissue after stimulation by cholera enterotoxin in vitro (38468). Addition of CT to suspensions of thymus, lymph node, spleen, or bone marrow cells in vitro resulted in a marked accumulation of cAMP with peak levels occurring 4-5 hr after incubation of cells with CT. Thymus cells showed the largest increase in cAMP, approximately 40-fold at 10 ng/ml CT. Bone marrow cells accumulated the least cAMP (1.5x), while intermediate levels were observed for spleen and lymph node cells (10-12x). Antiserum to CT prevented stimulation of increased cAMP levels. Repopulation studies using X-irradiated mice also showed that thymus-derived spleen cells accumulated more cAMP/10-7 cells than spleen cells from recipients given spleen or marrow cells. Spleen cells from athymic (nu/nu) mice also responded much less than did spleen cells from normal mice. Thymocytes appeared to bind CT to a greater degree than bone marrow cells. Spleen and lymph node cell suspensions also contained CT-binding cells and the number of CT-binding cells in these peripheral lymphoid tissues appeared approximately equal to the summation of the numbers observed in thymocyte and bone marrow cell suspensions. Stimulation of cAMP in lymphoid cells, especially thymocytes, by CT provides a pharmacological tool to investigate the mechanism and role of this nucleotide in the early events of antibody formation."} {"id": "PMID:165523", "title": "Isolation of a new enterovirus (38506).", "content": "During 1972 an apparently new enterovirus with characteristics of the Coxsackievirus group A was isolated from 11 residents of New York State, 10 of whom had central nervous system disease. The representative strain S/Albany 1/72 has the physical and chemical properties of an enterovirus and causes the pathology typical for Coxsackievirus group A in 1-day-old mice. Cross-neutralization tests indicated that the virus is distinct from currently recognized enteric viruses of man. Antibody levels to the representative strain were moderate to high in patients and were low to moderate in 26% of healthy individuals tested.", "contents": "Isolation of a new enterovirus (38506). During 1972 an apparently new enterovirus with characteristics of the Coxsackievirus group A was isolated from 11 residents of New York State, 10 of whom had central nervous system disease. The representative strain S/Albany 1/72 has the physical and chemical properties of an enterovirus and causes the pathology typical for Coxsackievirus group A in 1-day-old mice. Cross-neutralization tests indicated that the virus is distinct from currently recognized enteric viruses of man. Antibody levels to the representative strain were moderate to high in patients and were low to moderate in 26% of healthy individuals tested."} {"id": "PMID:165524", "title": "Preparation of rhinovirus antisera in the South American hystricomorph rodent, Octodon degus (38507).", "content": "Rhinovirus antisera have been prepared for rhinoviruses (RV) 7,9,26,32,67 and 87 in guinea pigs and in degus. Titers achieved were either similar in the 2 animals (RV7) somewhat higher in the degu (RV9 and RV32) or clearly higher in the degu (RV26, RV67 and RV87). Specificity of the antisera was similar in both animals. In special instances where it is difficult to prepare high-titered rhinovirus antisera in the guinea pig, the degu offers an attractive alternative source.", "contents": "Preparation of rhinovirus antisera in the South American hystricomorph rodent, Octodon degus (38507). Rhinovirus antisera have been prepared for rhinoviruses (RV) 7,9,26,32,67 and 87 in guinea pigs and in degus. Titers achieved were either similar in the 2 animals (RV7) somewhat higher in the degu (RV9 and RV32) or clearly higher in the degu (RV26, RV67 and RV87). Specificity of the antisera was similar in both animals. In special instances where it is difficult to prepare high-titered rhinovirus antisera in the guinea pig, the degu offers an attractive alternative source."} {"id": "PMID:165525", "title": "Stimulation of macromolecular synethesis in guinea pig cells by human CMV.", "content": "Nonproductive human CMV infection of G.P. embryo cells induced cellular RNA and DNA synthesis. RNA species synthesized in abortively infected G.P. cells included ribosomal 28S, 18S, and 4S transfer RNA. Virus inactivated with heat and UV light failed to induce cellular RNA and DNA synthesis. Evidence for increased DNA and RNA synthesis in infected cells was provided by studies of:(a) incorporation of thymidine and uridine, (b) extraction and separation of cellular DNA and RNA on sedimentation gradients, (c) autoradiography, and (d) measurement of mitotic index.", "contents": "Stimulation of macromolecular synethesis in guinea pig cells by human CMV. Nonproductive human CMV infection of G.P. embryo cells induced cellular RNA and DNA synthesis. RNA species synthesized in abortively infected G.P. cells included ribosomal 28S, 18S, and 4S transfer RNA. Virus inactivated with heat and UV light failed to induce cellular RNA and DNA synthesis. Evidence for increased DNA and RNA synthesis in infected cells was provided by studies of:(a) incorporation of thymidine and uridine, (b) extraction and separation of cellular DNA and RNA on sedimentation gradients, (c) autoradiography, and (d) measurement of mitotic index."} {"id": "PMID:165526", "title": "In vitro interaction of estrogen and prolactin on hormone-dependent rat mammory tumors (38511).", "content": "Hormone-dependent, regressing mammary tumors in rats were incubated in a chemically defined culture medium containing tritium labeled leucine at 37 degrees for 2 hr. The rate of tritium incorporation into the protein fraction by these tissues was measured with and without the addition of 17beta-estradiol and/or ovine prolactin into the medium. Tumor tissue responded to either estrogen or porlactin by a 6-7% increase in the rate of 3-H-leucine incorporation. When the incubation medium contained both the hormones, the increase in the rate of 3-H leucine incorporation was 19% which was significantly greater than the sum of the effect of each single hormone measured independelntly. These results demonstrate a synergistic effect between estrogen and prolactin on rat mammary tumors.", "contents": "In vitro interaction of estrogen and prolactin on hormone-dependent rat mammory tumors (38511). Hormone-dependent, regressing mammary tumors in rats were incubated in a chemically defined culture medium containing tritium labeled leucine at 37 degrees for 2 hr. The rate of tritium incorporation into the protein fraction by these tissues was measured with and without the addition of 17beta-estradiol and/or ovine prolactin into the medium. Tumor tissue responded to either estrogen or porlactin by a 6-7% increase in the rate of 3-H-leucine incorporation. When the incubation medium contained both the hormones, the increase in the rate of 3-H leucine incorporation was 19% which was significantly greater than the sum of the effect of each single hormone measured independelntly. These results demonstrate a synergistic effect between estrogen and prolactin on rat mammary tumors."} {"id": "PMID:165527", "title": "Glucose tolerance and pancreatic ultrastructure in mice with long-term diabetes induced by EMC virus (M variant) (38518).", "content": "Of 27 young male CD-1 mice infected with the M variant of the encephalomycarditis (EMC) virus and surviving for 11 or 12 mo, all but three had normal glucose tolerance curves, and all displayed normal islet cell morphology, at the time of sacrifice, in spite of an initital hyperglycemic response. Three animals maintained diabetic glucose tolerance curves one year after infection but they, too, failed to show significant morphological alterations in their pancreatic beta cells.", "contents": "Glucose tolerance and pancreatic ultrastructure in mice with long-term diabetes induced by EMC virus (M variant) (38518). Of 27 young male CD-1 mice infected with the M variant of the encephalomycarditis (EMC) virus and surviving for 11 or 12 mo, all but three had normal glucose tolerance curves, and all displayed normal islet cell morphology, at the time of sacrifice, in spite of an initital hyperglycemic response. Three animals maintained diabetic glucose tolerance curves one year after infection but they, too, failed to show significant morphological alterations in their pancreatic beta cells."} {"id": "PMID:165528", "title": "Photodynamic inactivation of herpesvirus hominins by methylene blue (38524).", "content": "Methylene blue, in a concentraion of 10-5M was virostatic in the presence of light but not in the dark for 31 of 37 strains of fresh isolates of herpesvirus hominis. Resistance to the dye developed during treatment. This photodynamic pattern was almost identical to that of neutral red which produced an identical effect. This was not ture for proflavine which was active in the dark in many instances. Cross insensitivity between proflavine and methylene blue was not observed.", "contents": "Photodynamic inactivation of herpesvirus hominins by methylene blue (38524). Methylene blue, in a concentraion of 10-5M was virostatic in the presence of light but not in the dark for 31 of 37 strains of fresh isolates of herpesvirus hominis. Resistance to the dye developed during treatment. This photodynamic pattern was almost identical to that of neutral red which produced an identical effect. This was not ture for proflavine which was active in the dark in many instances. Cross insensitivity between proflavine and methylene blue was not observed."} {"id": "PMID:165529", "title": "Comparison of the lipopretein profiles and the effect of N-phenylpropyl-N-benzyloxy acetamide in primates (38473).", "content": "Analytical ultracentrifugation showed Cebus and Rhesus monkeys had two low density components while only one was present in Squirrel monkeys. In untreated or W1372 treated monkeys, neither chylomicrons nor very low density lipoproteins were detected on analytical ultracentrifugation. Chylomicrons were not observed on agarose gel electrophoresis. Ultracentrifugal analysis showed W1372 treatment decreased the amount of LDL in all animals and also the HDL in Cebus monkeys on an atherogenic diet. Both untreated and W1372 treated Cebus monkeys on an atherogenic diet had abnormal amounts of LDL and HDL, while the LDL in treated animals occurred as multiple peaks. This was also evident on agarose gel electrophoresis. Accumulation of lipds in the liver and decrease of serum lipids indicated W1372 prevented release of lipoproteins from the liver.", "contents": "Comparison of the lipopretein profiles and the effect of N-phenylpropyl-N-benzyloxy acetamide in primates (38473). Analytical ultracentrifugation showed Cebus and Rhesus monkeys had two low density components while only one was present in Squirrel monkeys. In untreated or W1372 treated monkeys, neither chylomicrons nor very low density lipoproteins were detected on analytical ultracentrifugation. Chylomicrons were not observed on agarose gel electrophoresis. Ultracentrifugal analysis showed W1372 treatment decreased the amount of LDL in all animals and also the HDL in Cebus monkeys on an atherogenic diet. Both untreated and W1372 treated Cebus monkeys on an atherogenic diet had abnormal amounts of LDL and HDL, while the LDL in treated animals occurred as multiple peaks. This was also evident on agarose gel electrophoresis. Accumulation of lipds in the liver and decrease of serum lipids indicated W1372 prevented release of lipoproteins from the liver."} {"id": "PMID:165530", "title": "The effect of various prostaglandins and a prostaglandin synthetase inhibitor on rat anterior pituitary cyclic AMP levels and hormone release in vitro (38475).", "content": "(U)Prostaglandins E-1, E2,F-1alpha or F-2 alpha significantly increased the release of GH, with a parallel increase in intracellular cAMP concentrations, while they only protentiated HE-stimulated TSH release. (2) None of the prostaglandins examined consistently effected either the basal or HE-altered release of LH,FSH or prolactin. (3) The prostaglandin synthetase inhibitor, indomethacin, inhibited GH and TSH release and, at high doses of the drug, inhibited prolactin release. In contrast, the drug appeared to potentiate both He and sLRF-stimulated gonadotropin release. It had no significant effect on intracellular cAMP concentration.", "contents": "The effect of various prostaglandins and a prostaglandin synthetase inhibitor on rat anterior pituitary cyclic AMP levels and hormone release in vitro (38475). (U)Prostaglandins E-1, E2,F-1alpha or F-2 alpha significantly increased the release of GH, with a parallel increase in intracellular cAMP concentrations, while they only protentiated HE-stimulated TSH release. (2) None of the prostaglandins examined consistently effected either the basal or HE-altered release of LH,FSH or prolactin. (3) The prostaglandin synthetase inhibitor, indomethacin, inhibited GH and TSH release and, at high doses of the drug, inhibited prolactin release. In contrast, the drug appeared to potentiate both He and sLRF-stimulated gonadotropin release. It had no significant effect on intracellular cAMP concentration."} {"id": "PMID:165531", "title": "An improved method of fixation for immunofluorescent detection of SV40 T-antigen in infected human fibroblasts.", "content": "Improved fixation for immunofluorescence staining in the SV40 T-antigen test has been developed utilizing ethanol in place of acetone. The modified method improves resolution, results in smaller variability of cell numbers, and reduces the time of assay, while maintaining its sensitivity in discriminating between normal and cancer prone groups.", "contents": "An improved method of fixation for immunofluorescent detection of SV40 T-antigen in infected human fibroblasts. Improved fixation for immunofluorescence staining in the SV40 T-antigen test has been developed utilizing ethanol in place of acetone. The modified method improves resolution, results in smaller variability of cell numbers, and reduces the time of assay, while maintaining its sensitivity in discriminating between normal and cancer prone groups."} {"id": "PMID:165532", "title": "Stimulatory effects of peptides on growth of the free-living nematode Caenorhabditis briggsae.", "content": "Evidence is presented that peptide products of hydrolysis of casein, including some di- and tripeptides, but not the constituent amino acids, can stimulate growth of C. briggsae in defined basal medium supplemented with cytochrome C and B-sitosterol. Peptide activity may raise from amino acid imbalances in the medium which causes competitive inhibition of uptake of essential amino acids. Such activity precludes facilitation of heme transport as the sole function of growth factor in C. briggsae. This is the first report in a nutritional role of peptides in invertebrate metazoa.", "contents": "Stimulatory effects of peptides on growth of the free-living nematode Caenorhabditis briggsae. Evidence is presented that peptide products of hydrolysis of casein, including some di- and tripeptides, but not the constituent amino acids, can stimulate growth of C. briggsae in defined basal medium supplemented with cytochrome C and B-sitosterol. Peptide activity may raise from amino acid imbalances in the medium which causes competitive inhibition of uptake of essential amino acids. Such activity precludes facilitation of heme transport as the sole function of growth factor in C. briggsae. This is the first report in a nutritional role of peptides in invertebrate metazoa."} {"id": "PMID:165533", "title": "Effect of clofibrate on lipid metabolism in streptozotocin diabetic rats.", "content": "The effect of clofibrate (CPIB) on lipid metabolism was studied in male rats rendered diabetic by intravenous injection of 80 mg/kg of streptozotocin. After 1 wk, the rats received by gastric intubation 242 mg/kg/day of CPIB for 7 days. Liver lipid concentration remained unchanged in experimental diabetes and after treatment with CPIB; however, due to decreased liver weight, total liver lipids were lower in diabetic rats. Elevation of cholesterol, phospholipids, and triglycerides in the serum of diabetic rats was reversed by CPIB treatment. Hepatic cholesterol synthesis in diabetic rats was suppressed to approximately 1/10 of that in normal rats. Treatment with CPIB abolished this residual cholesterogenic activity. Diabetes had no effect on intestinal cholesterol synthesis; a slight increase was noted after CPIB treatment. Basal and norepinephrine-induced lipolysis in fat pads was elevated in diabetic rats; CPIB had no effect on these changes. The data show that the elevated serum lipids in diabetic rats are lowered by treatment with C-IB. It was concluded that the hypocholesterolemic activity of clofibrate in rats is not caused by its suppression of hepatic cholesterol synthesis.", "contents": "Effect of clofibrate on lipid metabolism in streptozotocin diabetic rats. The effect of clofibrate (CPIB) on lipid metabolism was studied in male rats rendered diabetic by intravenous injection of 80 mg/kg of streptozotocin. After 1 wk, the rats received by gastric intubation 242 mg/kg/day of CPIB for 7 days. Liver lipid concentration remained unchanged in experimental diabetes and after treatment with CPIB; however, due to decreased liver weight, total liver lipids were lower in diabetic rats. Elevation of cholesterol, phospholipids, and triglycerides in the serum of diabetic rats was reversed by CPIB treatment. Hepatic cholesterol synthesis in diabetic rats was suppressed to approximately 1/10 of that in normal rats. Treatment with CPIB abolished this residual cholesterogenic activity. Diabetes had no effect on intestinal cholesterol synthesis; a slight increase was noted after CPIB treatment. Basal and norepinephrine-induced lipolysis in fat pads was elevated in diabetic rats; CPIB had no effect on these changes. The data show that the elevated serum lipids in diabetic rats are lowered by treatment with C-IB. It was concluded that the hypocholesterolemic activity of clofibrate in rats is not caused by its suppression of hepatic cholesterol synthesis."} {"id": "PMID:165534", "title": "Effects of \"stress\" on pulsatile luteinizing hormone release in ovariectomized rats.", "content": "The effects ov various \"stresses\" on pulsatile LH release in ovariectomized rats were investigated. Blood was withdrawn through atrial cannulas and replaced with saline at 10 min intervals for 190 min. Plasma LH concentration was suppressed in rats subjected to 30 or 60 min of immobilization during the collection period. On the contrary, sham ovariectomy 4 hr prior to blood collection, leg break or iv injection of ACTH or corticosterone during the collection period did not alter pulsatile patterns in LH release. The results indicate that LH release mechanisms are highly resistant to \"stresses\" but that immobilization can suppress LH release by an unknown mechanism.", "contents": "Effects of \"stress\" on pulsatile luteinizing hormone release in ovariectomized rats. The effects ov various \"stresses\" on pulsatile LH release in ovariectomized rats were investigated. Blood was withdrawn through atrial cannulas and replaced with saline at 10 min intervals for 190 min. Plasma LH concentration was suppressed in rats subjected to 30 or 60 min of immobilization during the collection period. On the contrary, sham ovariectomy 4 hr prior to blood collection, leg break or iv injection of ACTH or corticosterone during the collection period did not alter pulsatile patterns in LH release. The results indicate that LH release mechanisms are highly resistant to \"stresses\" but that immobilization can suppress LH release by an unknown mechanism."} {"id": "PMID:165535", "title": "Effects of endurance exercise on serum enzyme activities in the dog, pig and man.", "content": "Daily levels of GOT, GPT, AK and LDH did not change consistently with exercise in any species. The level of CPK each day before exercise presented a consistent rise during the week of exercise in the dog and man but not in the pig. By the third day of resting, all enzyme activities were at control levels. The probable tissue of origin for AK and LDH at rest as well as after exercise was the heart, liver, skeletal muscle and kidney in all three species. Serum CPK was the most sensitive index of acute exercise stress in the trained dogs and men. We have shown that the pig, which exhibits responses to exercise resembling those of man, can be exercise trained. The pig may, therefore, be the more appropriate model for endurance exercise studies.", "contents": "Effects of endurance exercise on serum enzyme activities in the dog, pig and man. Daily levels of GOT, GPT, AK and LDH did not change consistently with exercise in any species. The level of CPK each day before exercise presented a consistent rise during the week of exercise in the dog and man but not in the pig. By the third day of resting, all enzyme activities were at control levels. The probable tissue of origin for AK and LDH at rest as well as after exercise was the heart, liver, skeletal muscle and kidney in all three species. Serum CPK was the most sensitive index of acute exercise stress in the trained dogs and men. We have shown that the pig, which exhibits responses to exercise resembling those of man, can be exercise trained. The pig may, therefore, be the more appropriate model for endurance exercise studies."} {"id": "PMID:165536", "title": "The effect of mycoplasmas on replication and plaquing ability of Herpes simplex virus.", "content": "M. arginini, an arginine utilizer, can decrease the yield of Herpes simplex virus, type 1 grown in Vero cells. M. arginini can also cause a reduction in number and size of plaques produced by HSV. The reduction in titer and plaque size produced in M. arginini-infected cells can be reversed by supplementing medium with additional arginine. A. laidlawii, a nonarginine utilizing mycoplasma, had no effect on the growth of HSV.", "contents": "The effect of mycoplasmas on replication and plaquing ability of Herpes simplex virus. M. arginini, an arginine utilizer, can decrease the yield of Herpes simplex virus, type 1 grown in Vero cells. M. arginini can also cause a reduction in number and size of plaques produced by HSV. The reduction in titer and plaque size produced in M. arginini-infected cells can be reversed by supplementing medium with additional arginine. A. laidlawii, a nonarginine utilizing mycoplasma, had no effect on the growth of HSV."} {"id": "PMID:165538", "title": "Malignant transformation of hamster cells following infection with bovine herpesvirus (infectious bovine rhinotracheitis virus.", "content": "Hamster embryo cells, following infection with IBR virus, showed malignant transformation. Hamsters of all ages, inbred or random bred, inoculated with two of the transformed cell lines developed solid tumors. Preliminary characterization of the tumors induced by one of the cell lines has indicated undifferentiated sarcomas. Viral specific antigen was detected in about 5% of the transformed cells and 10% of primary tumor cells in culture. Viral specific antibody was detected in the serum of tumor-bearing hamsters by the indirect immunofluorescent method, but no neutralizing antibodies were found. Infectious virus has not been recovered from either the transformed or tumor cells by cocultivation with bovine embryonic kidney cells.", "contents": "Malignant transformation of hamster cells following infection with bovine herpesvirus (infectious bovine rhinotracheitis virus. Hamster embryo cells, following infection with IBR virus, showed malignant transformation. Hamsters of all ages, inbred or random bred, inoculated with two of the transformed cell lines developed solid tumors. Preliminary characterization of the tumors induced by one of the cell lines has indicated undifferentiated sarcomas. Viral specific antigen was detected in about 5% of the transformed cells and 10% of primary tumor cells in culture. Viral specific antibody was detected in the serum of tumor-bearing hamsters by the indirect immunofluorescent method, but no neutralizing antibodies were found. Infectious virus has not been recovered from either the transformed or tumor cells by cocultivation with bovine embryonic kidney cells."} {"id": "PMID:165539", "title": "Tumor antigens in hamsters with sarcomas associated with herpesvirus type 2.", "content": "Tumor-associated antigens (TTA) were demonstrated in preparations of hamster sarcomas associated with Herpes simplex virus type 2, as well as in the sera of tumor-bearing hamsters. An immunoadsorption-in-gel method was employed to demonstrate and purify the TAA and anti-TAA. These results suggest the potential use of this technique for the demonstration of TAA or of anti-TAA in humans or animals with cancer.", "contents": "Tumor antigens in hamsters with sarcomas associated with herpesvirus type 2. Tumor-associated antigens (TTA) were demonstrated in preparations of hamster sarcomas associated with Herpes simplex virus type 2, as well as in the sera of tumor-bearing hamsters. An immunoadsorption-in-gel method was employed to demonstrate and purify the TAA and anti-TAA. These results suggest the potential use of this technique for the demonstration of TAA or of anti-TAA in humans or animals with cancer."} {"id": "PMID:165540", "title": "Neurohypophyseal hormones and analogues: magnesium dependence and contraction of arterial smooth muscle.", "content": "The present quantitative results, using isolated rat aorta, demonstrate that different [Mg2+]o (i.e. 0.2, 1.2 and 6.0 mM) potentiate the contractile actions of a variety of neuohypophyseal hormones and synthetic analogues on vascular smooth muscle. [Mg2+]o can alter both the hormone-receptor affinities (H-RA) and intrinsic (contractile) activities (i.a.) of these peptides on vascular muscle; 1.2 mM [Mg2+]o (approximately that found in rat plasma) appears to optimize H-RA and i.a. on rat aortic smooth muscle. The presence of [Mg2+]o not only steepens the concentration-effect curves to the neurohypophyseal peptides but increases the maximum contractile responses as well. The present findings question that [Mg+]o potentiates responses to neurohypophyseal peptides by vascular muscle solely by affecting H-RA. The present study supports the notion that Mg2+ potentiates responses to these peptides by acting at sites other than the receptor in mammalian vascular muscle. In addition, the present experiments suggest that the [Mg2+]o dependence of neurohypophyseal peptides on at lesast one mammalian vascular muscle-rat aorta- is directly rather than inversely proportional to the rat pressor potency of the molecules. Further, the vasopressin receptor which subserves contraction in mammalian blood vessels may differ in this respect from that in uterine smooth muscle.", "contents": "Neurohypophyseal hormones and analogues: magnesium dependence and contraction of arterial smooth muscle. The present quantitative results, using isolated rat aorta, demonstrate that different [Mg2+]o (i.e. 0.2, 1.2 and 6.0 mM) potentiate the contractile actions of a variety of neuohypophyseal hormones and synthetic analogues on vascular smooth muscle. [Mg2+]o can alter both the hormone-receptor affinities (H-RA) and intrinsic (contractile) activities (i.a.) of these peptides on vascular muscle; 1.2 mM [Mg2+]o (approximately that found in rat plasma) appears to optimize H-RA and i.a. on rat aortic smooth muscle. The presence of [Mg2+]o not only steepens the concentration-effect curves to the neurohypophyseal peptides but increases the maximum contractile responses as well. The present findings question that [Mg+]o potentiates responses to neurohypophyseal peptides by vascular muscle solely by affecting H-RA. The present study supports the notion that Mg2+ potentiates responses to these peptides by acting at sites other than the receptor in mammalian vascular muscle. In addition, the present experiments suggest that the [Mg2+]o dependence of neurohypophyseal peptides on at lesast one mammalian vascular muscle-rat aorta- is directly rather than inversely proportional to the rat pressor potency of the molecules. Further, the vasopressin receptor which subserves contraction in mammalian blood vessels may differ in this respect from that in uterine smooth muscle."} {"id": "PMID:165541", "title": "Enhancement of interferon production in vitro: a property of tilorone-poly rL:rC/DEAE-Dextran.", "content": "Tilorone and Poly rI:rC, in the presence of DEAE-dextran, were found to exhibit a marked synergism with respect to the induction of interferon in L929 and primary mouse embryo fibroblasts, but not human foreskin fibroblasts, in cell cultures. The degree of synergism was proportional to the concentrations of tilorone and Poly rI:rC and was influenced by the times of addition of the compounds relative to each other.", "contents": "Enhancement of interferon production in vitro: a property of tilorone-poly rL:rC/DEAE-Dextran. Tilorone and Poly rI:rC, in the presence of DEAE-dextran, were found to exhibit a marked synergism with respect to the induction of interferon in L929 and primary mouse embryo fibroblasts, but not human foreskin fibroblasts, in cell cultures. The degree of synergism was proportional to the concentrations of tilorone and Poly rI:rC and was influenced by the times of addition of the compounds relative to each other."} {"id": "PMID:165542", "title": "The inhibitory effects of MgCl2 on the inactivation kinetics of poliovirus by urea.", "content": "By analyzing the inhibitory effects of Mg-2+ on the three-stage urea inactivation curve of poliovirus, it was concluded that urea inactivates poliovirus via a two-step reaction as follows: urea initially converts the native virus into an intermediate state which is still infectious but is now highly sensitive to inactivation. This reaction is unaffected by Mg-2+ and is reversible. In the subsequent reaction, the sensitized virus is either irreversibly inactivated by urea or reversibly stablized by Mg-2+. In addition, the inactivation curve revealed that a fraction of relatively stable virus population was established in the presence of urea and that the size of this persistent virus population depended on the concentration of urea. It was not determined whether urea induced the formation of this stable fraction of virus or merely selected for a preexisting stable population of virus. However, evidence was presented that (1) the persistent virus population was not due to the depletion or inactivation of urea in the sample, (2) whatever stabilized the virus, it could not be removed or reversed by simple dilution as in the case of Mg-2+, (3) no excess stabilizing material was made to stabilize the addition of untreated virus and finally (4) the persistent virus population was resistant to that concentration of urea in which it was observed but could be further inactivated by a higher concentration of urea, only to result in a smaller fraction of persistent virus population.", "contents": "The inhibitory effects of MgCl2 on the inactivation kinetics of poliovirus by urea. By analyzing the inhibitory effects of Mg-2+ on the three-stage urea inactivation curve of poliovirus, it was concluded that urea inactivates poliovirus via a two-step reaction as follows: urea initially converts the native virus into an intermediate state which is still infectious but is now highly sensitive to inactivation. This reaction is unaffected by Mg-2+ and is reversible. In the subsequent reaction, the sensitized virus is either irreversibly inactivated by urea or reversibly stablized by Mg-2+. In addition, the inactivation curve revealed that a fraction of relatively stable virus population was established in the presence of urea and that the size of this persistent virus population depended on the concentration of urea. It was not determined whether urea induced the formation of this stable fraction of virus or merely selected for a preexisting stable population of virus. However, evidence was presented that (1) the persistent virus population was not due to the depletion or inactivation of urea in the sample, (2) whatever stabilized the virus, it could not be removed or reversed by simple dilution as in the case of Mg-2+, (3) no excess stabilizing material was made to stabilize the addition of untreated virus and finally (4) the persistent virus population was resistant to that concentration of urea in which it was observed but could be further inactivated by a higher concentration of urea, only to result in a smaller fraction of persistent virus population."} {"id": "PMID:165543", "title": "Evidence for conformational states of poliovirions: effects of cations on reactivity of poliovirions to guanidine.", "content": "The kinetics of inactivation of poliovirions were determined in the presence of various concentrations of monovalent and divalent ions, methionine, guanidine and combinations of these at various temperatures. Four states of the virion, under control of the ionic environment, could be recognized which were reversibly interchangeable and yet retained infectious potential. These states were detected by differential sensitivity of the virion to inactivation of infectivity by heat, urea and guanidine. The data are interpreted in terms of conformational structural changes under control of the ionic environment. It is proposed that these various structural conformations are meaningful to the various biologic functional states of the virus.", "contents": "Evidence for conformational states of poliovirions: effects of cations on reactivity of poliovirions to guanidine. The kinetics of inactivation of poliovirions were determined in the presence of various concentrations of monovalent and divalent ions, methionine, guanidine and combinations of these at various temperatures. Four states of the virion, under control of the ionic environment, could be recognized which were reversibly interchangeable and yet retained infectious potential. These states were detected by differential sensitivity of the virion to inactivation of infectivity by heat, urea and guanidine. The data are interpreted in terms of conformational structural changes under control of the ionic environment. It is proposed that these various structural conformations are meaningful to the various biologic functional states of the virus."} {"id": "PMID:165544", "title": "Effect of ascorbic acid on rhinovirus replication in WI-38 cells.", "content": "Exposure of WI-38 cells to ascorbic acid plus glutathione mixtures in growth medium for 2 days prior to infection with rhinovirus serotype 20 and during virus replication suppressed multicyclic but not single-cycle growth of the virus. Multicyclic growth was suppressed over the range of multiplicity of infection (m.o.i.) of 4 times 10-minus 1 minus 4 times 10-minus 4 PFU/cell. There was some suggestion that, in the presence of ascorbic acid plus glutathione, interferon was produced at the highest m.o.i. tested but at barely detectable levels.", "contents": "Effect of ascorbic acid on rhinovirus replication in WI-38 cells. Exposure of WI-38 cells to ascorbic acid plus glutathione mixtures in growth medium for 2 days prior to infection with rhinovirus serotype 20 and during virus replication suppressed multicyclic but not single-cycle growth of the virus. Multicyclic growth was suppressed over the range of multiplicity of infection (m.o.i.) of 4 times 10-minus 1 minus 4 times 10-minus 4 PFU/cell. There was some suggestion that, in the presence of ascorbic acid plus glutathione, interferon was produced at the highest m.o.i. tested but at barely detectable levels."} {"id": "PMID:165545", "title": "Resticted growth of human cytomegalovirus in UV-irradiated WI-38 human fibroblasts.", "content": "The growth of human CMV was inhibited by uv irradiation of cells prior to infection or during the 48-hr latent period of virus replication but not after virus synthesis began. The duration of uv exposure sufficient to inhibit CMV replication was insufficient to inhibit replication of Herpes simplex and did not prevent uninfected cells from dividing normally. The effect of uv irradiation on CMV replication may have been mediated through prevention of the virus on host cell RNA(s) synthesis.", "contents": "Resticted growth of human cytomegalovirus in UV-irradiated WI-38 human fibroblasts. The growth of human CMV was inhibited by uv irradiation of cells prior to infection or during the 48-hr latent period of virus replication but not after virus synthesis began. The duration of uv exposure sufficient to inhibit CMV replication was insufficient to inhibit replication of Herpes simplex and did not prevent uninfected cells from dividing normally. The effect of uv irradiation on CMV replication may have been mediated through prevention of the virus on host cell RNA(s) synthesis."} {"id": "PMID:165546", "title": "Adipose tissue glycerokinase activity in genetic and acquired obesity in rats and mice.", "content": "Glycerokinase activity in isolated fat cells was elevated in both Ob/Ob and Db/Db mice in comparison to their lean controls and this elevation was associated with obesity, hyperinsulinemia and hyperglycemia. In the other forms of acquired and genetic obesity in the rats and mice studied (also associated with hyperinsulinemia), adipose tissue glycerokinase activity was not elevated in comparison to lean control groups when expressed on a mg protein basis. It is concluded that the elevated glycerokinase activity is not due to the specific Db or Ob mutation, but is secondary to the obesity and hyperinsulinemia interacting with the similar genetic background in the C57BL/KsJ and the C57BL/6J mouse strains.", "contents": "Adipose tissue glycerokinase activity in genetic and acquired obesity in rats and mice. Glycerokinase activity in isolated fat cells was elevated in both Ob/Ob and Db/Db mice in comparison to their lean controls and this elevation was associated with obesity, hyperinsulinemia and hyperglycemia. In the other forms of acquired and genetic obesity in the rats and mice studied (also associated with hyperinsulinemia), adipose tissue glycerokinase activity was not elevated in comparison to lean control groups when expressed on a mg protein basis. It is concluded that the elevated glycerokinase activity is not due to the specific Db or Ob mutation, but is secondary to the obesity and hyperinsulinemia interacting with the similar genetic background in the C57BL/KsJ and the C57BL/6J mouse strains."} {"id": "PMID:165547", "title": "Differentiation of nephrotensin from the renin angiotensin system.", "content": "An investigation of the relationship between nephrotensin and the renin angiotensin system was carred out. Nephrotensin was found in the plasma of rats with renal clip hypertension and with chemically induced kidney damage. There was no demonstrable correlation between presence of nephrotensin and plasma renin activity, and the pressor activity of nephrotensin was not altered by previous immunization of test animals with angiotensin II nor by pretreatment with angiotensin I converting enzyme inhibitor. These results indicate that nephrotensin is different from the components of the renin-angiotensin system.", "contents": "Differentiation of nephrotensin from the renin angiotensin system. An investigation of the relationship between nephrotensin and the renin angiotensin system was carred out. Nephrotensin was found in the plasma of rats with renal clip hypertension and with chemically induced kidney damage. There was no demonstrable correlation between presence of nephrotensin and plasma renin activity, and the pressor activity of nephrotensin was not altered by previous immunization of test animals with angiotensin II nor by pretreatment with angiotensin I converting enzyme inhibitor. These results indicate that nephrotensin is different from the components of the renin-angiotensin system."} {"id": "PMID:165549", "title": "Modification of surface membrane antigens by trypsin.", "content": "Cultured 3T3 and PY-3T3 mouse fibroblasts were subjected to mild treatment with twice crystallized trypsin and their immunogenicity tested in ICR/CD-1 mice. Surface antigenic modifications were observed using the foot pad swelling assay for detection of delayed hypersensitive responses. Mice immunized with trypsin-treated 3T3 cells showed cell-mediated immune reactions following challenge with either homologous antigen or untreated PY-3T3 fibroblasts. In contrast, treatment of the virus-transformed cells with trypsin decreased their antigenicity as determined by this in vivo assay.", "contents": "Modification of surface membrane antigens by trypsin. Cultured 3T3 and PY-3T3 mouse fibroblasts were subjected to mild treatment with twice crystallized trypsin and their immunogenicity tested in ICR/CD-1 mice. Surface antigenic modifications were observed using the foot pad swelling assay for detection of delayed hypersensitive responses. Mice immunized with trypsin-treated 3T3 cells showed cell-mediated immune reactions following challenge with either homologous antigen or untreated PY-3T3 fibroblasts. In contrast, treatment of the virus-transformed cells with trypsin decreased their antigenicity as determined by this in vivo assay."} {"id": "PMID:165548", "title": "A specific complement-fixation test for human hepatitis a employing CR326 virus antigen. Diagnosis and epidemiology.", "content": "A specific diagnostic complement-fixation test for hepatitis A antibody in human serum was described employing livers of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A CF antibody shortly after the onset of illness and this persisted thereafter. Good agreement was noted in the development of CF and neutralizing antibodies in hepatitis A cases. Hepatitis A was shown to occur in a person with hepatitis B antigenemia and hepatitis B occurred in persons with hepatitis A antibody. Most persons with hepatitis A who were tested, but none of those with hepatitis B, developed increased anticomplementary activity in their sera at the time of onset of illness. At least one patient with hepatitis A developed antibody against normal liver that persisted. The possible inplications of this in relation to pathogenesis and to non-specific diagnostic tests in hepatitis were discussed. A limited epidemiologic study of a family outbreak of hepatitis in Costa Rica and of a group of young adults in our epidemic country acquire their infections at an early age and are immune thereafter; persons in areas of relatively low incidence may proceed into adulthood without experience with hepatitis A. The CF test should provide an excellent tool for diagnosis and for epidemiologic investigation of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture.", "contents": "A specific complement-fixation test for human hepatitis a employing CR326 virus antigen. Diagnosis and epidemiology. A specific diagnostic complement-fixation test for hepatitis A antibody in human serum was described employing livers of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A CF antibody shortly after the onset of illness and this persisted thereafter. Good agreement was noted in the development of CF and neutralizing antibodies in hepatitis A cases. Hepatitis A was shown to occur in a person with hepatitis B antigenemia and hepatitis B occurred in persons with hepatitis A antibody. Most persons with hepatitis A who were tested, but none of those with hepatitis B, developed increased anticomplementary activity in their sera at the time of onset of illness. At least one patient with hepatitis A developed antibody against normal liver that persisted. The possible inplications of this in relation to pathogenesis and to non-specific diagnostic tests in hepatitis were discussed. A limited epidemiologic study of a family outbreak of hepatitis in Costa Rica and of a group of young adults in our epidemic country acquire their infections at an early age and are immune thereafter; persons in areas of relatively low incidence may proceed into adulthood without experience with hepatitis A. The CF test should provide an excellent tool for diagnosis and for epidemiologic investigation of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture."} {"id": "PMID:165550", "title": "Protein and RNA synthesis in follicles isolated from rabbit ovaries.", "content": "The in vitro synthesis of protein and RNA in follicles from mated and unmated rabbits has been studied by measuring precursor incorporation. Radioactive methionine incorporation into follicular proteins showed a transitory rise following coitus but fell to precoital levels in ovulated follicles. LH, FSH, and cyclic AMP all exerted an acute stimulatory action on the incorporation of amino acids into proteins by follicles from unmated rabbits. Radioactive uridine incorporation into follicular RNA showed the same temporal pattern of postcoital rise followed by a decline in incorporation rates in the period around ovulation. In acute incubations, FSH and cyclic AMP stimulated RNA synthesis; LH was without acute action on this process. The results of these studies suggest that a wave of follicular protein and RNA synthesis precedes ovulation and may be partly related to the preovulatory surge in gonadotropins.", "contents": "Protein and RNA synthesis in follicles isolated from rabbit ovaries. The in vitro synthesis of protein and RNA in follicles from mated and unmated rabbits has been studied by measuring precursor incorporation. Radioactive methionine incorporation into follicular proteins showed a transitory rise following coitus but fell to precoital levels in ovulated follicles. LH, FSH, and cyclic AMP all exerted an acute stimulatory action on the incorporation of amino acids into proteins by follicles from unmated rabbits. Radioactive uridine incorporation into follicular RNA showed the same temporal pattern of postcoital rise followed by a decline in incorporation rates in the period around ovulation. In acute incubations, FSH and cyclic AMP stimulated RNA synthesis; LH was without acute action on this process. The results of these studies suggest that a wave of follicular protein and RNA synthesis precedes ovulation and may be partly related to the preovulatory surge in gonadotropins."} {"id": "PMID:165558", "title": "CD spectra and redox reactions of superoxide dismutase from Escherichia coli B: evidence for a Mn(III) enzyme.", "content": "Analysis of the metal content, CD and EPR spectra, and reaction with H(2)O(2) and ferrocyanide have been carried out on E. coli superoxide dismutase, which contains manganese as the metal prosthetic group. The results obtained indicate that the metal is present in the enzyme as a high spin Mn(III) complex of highly distorted octahedral symmetry, in the ratio of approximately 1 atom of manganese per enzyme dimer.", "contents": "CD spectra and redox reactions of superoxide dismutase from Escherichia coli B: evidence for a Mn(III) enzyme. Analysis of the metal content, CD and EPR spectra, and reaction with H(2)O(2) and ferrocyanide have been carried out on E. coli superoxide dismutase, which contains manganese as the metal prosthetic group. The results obtained indicate that the metal is present in the enzyme as a high spin Mn(III) complex of highly distorted octahedral symmetry, in the ratio of approximately 1 atom of manganese per enzyme dimer."} {"id": "PMID:165569", "title": "Evidence for a lesion in carbohydrate metabolism in fatty liver and kidney syndrome in chicks.", "content": "Liver and kidney slices from chicks affected with fatty liver and kidney syndrome (FLKS) were incubated in vitro with a variety of non-carbohydrate precursors and their ability to form glucose was studied. The results show that the affected liver was unable to form significant quantities of glucose from the precursors (gluconeogenesis). Glycogen breakdown was also drastically reduced because the tissue was almost devoid of this carbohydrate store. Blood chemistry revealed no evidence of overall liver malfunction but reflected the consequences of lack of gluconeogenesis. In contrast, kidney gluconeogenic activity was significantly higher than in the controls, suggesting an attempt by this organ to offset the reduced hepatic capability. Attempts to restore activity in vitro were made by adding known cofactors of gluconeogenesis. Asmall but significant improvement resulted from addition of biotin to liver slices.", "contents": "Evidence for a lesion in carbohydrate metabolism in fatty liver and kidney syndrome in chicks. Liver and kidney slices from chicks affected with fatty liver and kidney syndrome (FLKS) were incubated in vitro with a variety of non-carbohydrate precursors and their ability to form glucose was studied. The results show that the affected liver was unable to form significant quantities of glucose from the precursors (gluconeogenesis). Glycogen breakdown was also drastically reduced because the tissue was almost devoid of this carbohydrate store. Blood chemistry revealed no evidence of overall liver malfunction but reflected the consequences of lack of gluconeogenesis. In contrast, kidney gluconeogenic activity was significantly higher than in the controls, suggesting an attempt by this organ to offset the reduced hepatic capability. Attempts to restore activity in vitro were made by adding known cofactors of gluconeogenesis. Asmall but significant improvement resulted from addition of biotin to liver slices."} {"id": "PMID:165570", "title": "Serum alkaline phosphatase activity in relation to liveweight of lambs.", "content": "Groups of lambs were fed four levels of a diet based upon oaten grain. Two groups gained weight rapidly, one less rapidly and the other lost liveweight over a 32-day period. Serum alkaline phosphatase activity was found to be closely correlated to liveweight, in a positive linear manner, in those lambs gaining weight rapidly. This relationship was similar in lambs of R or r blood group. Supplementation of the diet with limestone and or sodium chloride did not influence the relationship. This relationship is considered to reflect the influence of the dietary treatments upon the rate of skeletal metabolism.", "contents": "Serum alkaline phosphatase activity in relation to liveweight of lambs. Groups of lambs were fed four levels of a diet based upon oaten grain. Two groups gained weight rapidly, one less rapidly and the other lost liveweight over a 32-day period. Serum alkaline phosphatase activity was found to be closely correlated to liveweight, in a positive linear manner, in those lambs gaining weight rapidly. This relationship was similar in lambs of R or r blood group. Supplementation of the diet with limestone and or sodium chloride did not influence the relationship. This relationship is considered to reflect the influence of the dietary treatments upon the rate of skeletal metabolism."} {"id": "PMID:165571", "title": "A comparison in calves of the antigenicity of three strains of bovid herpesvirus 2.", "content": "Three strains of bovid herpesvirus 2, viz. Allerton, bovine mammillitis and 69/1LO were used to infect calves intradermally. Twenty-eight days later the immunity of the calves was challenged by intravenous injection of a homologous or heterologous strain. Challenge control calves developed a fever (greater than 40 degrees C) lasting several days and widespread skin lesions which varied with the strain. Homologous challenge of the primary infection produced neither skin lesions nor febrile response, except in one calf in which fever was noted on one day. Heterologous challenge did not cause skin lesions but fever occurred in 8/12 calves. In particular Allerton virus failed to protect completely against heterologous challenge. Despite minor differences evident in these experiments, it is recommended that these isolates should be considered as strains of the same virus--bovid herpesvirus 2.", "contents": "A comparison in calves of the antigenicity of three strains of bovid herpesvirus 2. Three strains of bovid herpesvirus 2, viz. Allerton, bovine mammillitis and 69/1LO were used to infect calves intradermally. Twenty-eight days later the immunity of the calves was challenged by intravenous injection of a homologous or heterologous strain. Challenge control calves developed a fever (greater than 40 degrees C) lasting several days and widespread skin lesions which varied with the strain. Homologous challenge of the primary infection produced neither skin lesions nor febrile response, except in one calf in which fever was noted on one day. Heterologous challenge did not cause skin lesions but fever occurred in 8/12 calves. In particular Allerton virus failed to protect completely against heterologous challenge. Despite minor differences evident in these experiments, it is recommended that these isolates should be considered as strains of the same virus--bovid herpesvirus 2."} {"id": "PMID:165572", "title": "The incidence of antibody to infectious bovine rhinotracheitis virus in Kenyan cattle.", "content": "A total of 3204 cattle sera, collected between 1966 and 1974, from all seven provinces and 34 of the 42 districts of Kenya were screened in a neutralisation test for antibody to infectious bovine rhinotracheitis virus (IBRV). Antibody to IBRV was found in some sera from all the districts, with cattle over two years old showing the highest incidence. A small number of goat sera also showed some antibody. From the results obtained it is concluded that IBRV infection is widespread in Kenyan cattle.", "contents": "The incidence of antibody to infectious bovine rhinotracheitis virus in Kenyan cattle. A total of 3204 cattle sera, collected between 1966 and 1974, from all seven provinces and 34 of the 42 districts of Kenya were screened in a neutralisation test for antibody to infectious bovine rhinotracheitis virus (IBRV). Antibody to IBRV was found in some sera from all the districts, with cattle over two years old showing the highest incidence. A small number of goat sera also showed some antibody. From the results obtained it is concluded that IBRV infection is widespread in Kenyan cattle."} {"id": "PMID:165573", "title": "Comparison of three methods for sampling the bovine upper respiratory tract for viruses.", "content": "A modified naso-pharyngeal swab with nylon bristles had certain advantages for sampling the bovine upper respiratory tract for viruses. The titre of parainfluenza virus type 3 recovered was greatest when this type of swab was used compared with two other methods of sampling.", "contents": "Comparison of three methods for sampling the bovine upper respiratory tract for viruses. A modified naso-pharyngeal swab with nylon bristles had certain advantages for sampling the bovine upper respiratory tract for viruses. The titre of parainfluenza virus type 3 recovered was greatest when this type of swab was used compared with two other methods of sampling."} {"id": "PMID:165574", "title": "[Diagnostic value of bone scintigraphy with technetium pyrophosphate. Study of 250 patients].", "content": "The authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear.", "contents": "[Diagnostic value of bone scintigraphy with technetium pyrophosphate. Study of 250 patients]. The authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear."} {"id": "PMID:165576", "title": "Stress polycythemia--a pathophysiologic study.", "content": "Two patients with \"Gaisb\u00f6ck syndrome\" (stress polycythemia) were found to have been under chronic \"stress\" with REM sleep decrease, decreased nocturnal ADH-like activity and consequent nocturnal water loss. The role of REM decrease with chronic \"stress\" in causing secondary decrease in nocturnal ADH-like activity was emphasized as the means by which \"stress\" caused the blood volume changes seen with these two patients. Some factors that possibly could play a role in the pathophysiology of this syndrome were ruled out and other factors not studied here were considered for future investigation.", "contents": "Stress polycythemia--a pathophysiologic study. Two patients with \"Gaisb\u00f6ck syndrome\" (stress polycythemia) were found to have been under chronic \"stress\" with REM sleep decrease, decreased nocturnal ADH-like activity and consequent nocturnal water loss. The role of REM decrease with chronic \"stress\" in causing secondary decrease in nocturnal ADH-like activity was emphasized as the means by which \"stress\" caused the blood volume changes seen with these two patients. Some factors that possibly could play a role in the pathophysiology of this syndrome were ruled out and other factors not studied here were considered for future investigation."} {"id": "PMID:165577", "title": "The prevention of iron dificency anemia in infants.", "content": "The prevention of iron deficiency requires attention to the toal feeding regimen as well as to its iron content. The use of fresh cow's milk in early infancy, a common practice, is associated with the development of measurable degrees of iron deficiency. In many instances excessive amounts of milk produce severe iron deficiency anemia during the second year of life in infants of greater than average birth weight. The psychological factors leading to such milk intakes have been reviewed. Present evidence supports the hypothesis that occult blood loss is a major etiologic factor in iron deficiency in infancy. Although the mechaisms of intestinal damage by fresh cow's milk protein is highly suspect and that the concentration of protein in the formula may play a significant role. What about iron fortification of infant formulas? Itis becoming clear that fullterm infants fed prepared formulas having protein concentrations approaching that of human milk and fed diets containing about 7 mg of iron daily after the age of 3 months infrequently develop biochemical iron deficiency. The addition of iron to the formula at levels of 10 to 12 mg/gt is assurance that their intake is adequate, whatever the iron intake from other foods. Low-birth-weight infants have increased iron needs because of their rapid growth. Iron-ofrtified formulas are necessary for these infants. Since iron from fortified formulas is well absorbed during the first three months of life, even if it is not immediately used for hemoglobin formation, an inccrease in the iron stores will occur...", "contents": "The prevention of iron dificency anemia in infants. The prevention of iron deficiency requires attention to the toal feeding regimen as well as to its iron content. The use of fresh cow's milk in early infancy, a common practice, is associated with the development of measurable degrees of iron deficiency. In many instances excessive amounts of milk produce severe iron deficiency anemia during the second year of life in infants of greater than average birth weight. The psychological factors leading to such milk intakes have been reviewed. Present evidence supports the hypothesis that occult blood loss is a major etiologic factor in iron deficiency in infancy. Although the mechaisms of intestinal damage by fresh cow's milk protein is highly suspect and that the concentration of protein in the formula may play a significant role. What about iron fortification of infant formulas? Itis becoming clear that fullterm infants fed prepared formulas having protein concentrations approaching that of human milk and fed diets containing about 7 mg of iron daily after the age of 3 months infrequently develop biochemical iron deficiency. The addition of iron to the formula at levels of 10 to 12 mg/gt is assurance that their intake is adequate, whatever the iron intake from other foods. Low-birth-weight infants have increased iron needs because of their rapid growth. Iron-ofrtified formulas are necessary for these infants. Since iron from fortified formulas is well absorbed during the first three months of life, even if it is not immediately used for hemoglobin formation, an inccrease in the iron stores will occur..."} {"id": "PMID:165578", "title": "Glycogen content in the adrenals and liver of rat embryos depending on the level of adrenocorticotropic functions.", "content": "The functional state of the adrenals of rats during prenatal development was studied. The accumulation of glycogen in the adrenals and liver in 15.5-21.5-day old embryos was used as the index. The maximum glycogen concentration in the adrenals and the minimum in the liver were detected in 15.5-16.5-day embryos, i.e., before the adrenals had begun to produce glucocorticoids. A sharp decrease in glycogen in the adrenals was observed in 17.5-day embryos, and an appreciable accumulation in the liver in 18.5-day embryos, which coincides with the beginning of the glucocorticoid function. Decapitation and encephalectomy performed at an age of 17.5-19.5 days of development of the embryos, were invariably accompanied by a significant increase in the glycogen content in the adrenals and a decrease in its level in the liver in the case of investigation after two days. This indicates an active participation of the hypothalamo-pituitary system in the regulation of the adrenocortical function in the late days of embryonic development.", "contents": "Glycogen content in the adrenals and liver of rat embryos depending on the level of adrenocorticotropic functions. The functional state of the adrenals of rats during prenatal development was studied. The accumulation of glycogen in the adrenals and liver in 15.5-21.5-day old embryos was used as the index. The maximum glycogen concentration in the adrenals and the minimum in the liver were detected in 15.5-16.5-day embryos, i.e., before the adrenals had begun to produce glucocorticoids. A sharp decrease in glycogen in the adrenals was observed in 17.5-day embryos, and an appreciable accumulation in the liver in 18.5-day embryos, which coincides with the beginning of the glucocorticoid function. Decapitation and encephalectomy performed at an age of 17.5-19.5 days of development of the embryos, were invariably accompanied by a significant increase in the glycogen content in the adrenals and a decrease in its level in the liver in the case of investigation after two days. This indicates an active participation of the hypothalamo-pituitary system in the regulation of the adrenocortical function in the late days of embryonic development."} {"id": "PMID:165580", "title": "The in vivo uptake of tritiated estradiol in carcinoma of the breast.", "content": "In human beings, the uptake of radiolabeled estradiol suppressed by carcinomatous breast tissue in vivo in relation to adipose breast tissue has been studied in 20 patients. The ratio of tumor uptake to fat tissue uptake was correlated with the age of the patient, menopausal status, presence of axillary metastases at time of mastectomy, and the response to endocrine therapy if metastases were presented. There was no correlation between a higher uptake of estradiol by the tumor and age of the patient, menopausal status, or presence of axillary metastases at time of mastectomy. Patients with a higher uptake of estradiol tended to respond favorably to endocrine treatment.", "contents": "The in vivo uptake of tritiated estradiol in carcinoma of the breast. In human beings, the uptake of radiolabeled estradiol suppressed by carcinomatous breast tissue in vivo in relation to adipose breast tissue has been studied in 20 patients. The ratio of tumor uptake to fat tissue uptake was correlated with the age of the patient, menopausal status, presence of axillary metastases at time of mastectomy, and the response to endocrine therapy if metastases were presented. There was no correlation between a higher uptake of estradiol by the tumor and age of the patient, menopausal status, or presence of axillary metastases at time of mastectomy. Patients with a higher uptake of estradiol tended to respond favorably to endocrine treatment."} {"id": "PMID:165581", "title": "Glandular tumors of the palate.", "content": "Salivary gland tumors of the palate originate in the minor salivary glands located in the glandular zone of the palate. Approximately 7 per cent of all tumors of the salivary gland occur in the palate, and approximately one-half of such tumors are cancers. The salivary gland tumor is more often found in the hard palate. Of the 90 salivary gland tumors of the palate reported herein, 49 per cent were benign, and all were pleomorphic adenomas. Of the cancers, 70 per cent were cylindromas, 15 per cent mucoepidermoid cancers, and the remaining 15 per cent included acinic cell carcinomas, undifferentiated carcinomas, and papillary adenocarcinomas. There is a 50 per cent likelihood of a lump in the palate in the glandular zone being a cancer. The simplistic diagnosis of a cyst should be considered only after other lesions have been excluded. The recommended form of treatment is surgical excision. Fenestration of the palate is a potential consequence of excision in 30 to 60 per cent of patients, depending upon whether or not the lesion is benign or malignant. The results of surgical treatment are good, but fenestration shoud be accepted as a necessary result of adequate treatment. Surgical treatment of cylindromas continues to be most difficult and demands the utmost of that intangible essence known as surgical judgment. Radiotherapy has been considered as a palliative agent for the treatment of inoperable and recurring cancers, especially cylindromas.", "contents": "Glandular tumors of the palate. Salivary gland tumors of the palate originate in the minor salivary glands located in the glandular zone of the palate. Approximately 7 per cent of all tumors of the salivary gland occur in the palate, and approximately one-half of such tumors are cancers. The salivary gland tumor is more often found in the hard palate. Of the 90 salivary gland tumors of the palate reported herein, 49 per cent were benign, and all were pleomorphic adenomas. Of the cancers, 70 per cent were cylindromas, 15 per cent mucoepidermoid cancers, and the remaining 15 per cent included acinic cell carcinomas, undifferentiated carcinomas, and papillary adenocarcinomas. There is a 50 per cent likelihood of a lump in the palate in the glandular zone being a cancer. The simplistic diagnosis of a cyst should be considered only after other lesions have been excluded. The recommended form of treatment is surgical excision. Fenestration of the palate is a potential consequence of excision in 30 to 60 per cent of patients, depending upon whether or not the lesion is benign or malignant. The results of surgical treatment are good, but fenestration shoud be accepted as a necessary result of adequate treatment. Surgical treatment of cylindromas continues to be most difficult and demands the utmost of that intangible essence known as surgical judgment. Radiotherapy has been considered as a palliative agent for the treatment of inoperable and recurring cancers, especially cylindromas."} {"id": "PMID:165582", "title": "Clinical course of cystosarcoma phyllodes related to histologic appearance.", "content": "A series of 17 females having cystosarcoma phyllodes underwent surgical treatment. The subsequent clinical course was observed periodically. Twelve patients had originally histologically benign tumors. Six patients had a recurrence, and of these, malignant characteristics developed in four instances. Five patients had originally histologically malignant tumors. Recurrences were encountered in four. Five patients died from a generalized spread of the tumor. Three of these patients had originally histologically benign tumors, in which malignant features of the recurrent tumor subsequently developed. The surgical treatment ranged from local excision to simple mastectomy with additional roentgenotherapy in three. Neither procedure prevented a recurrence from the original tumor, whether benign or malignant. Poor correlation exists between biologic behavior and histologic appearance of cystosarcoma phyllodes, independent of the surgical procedure. Wide local excision in histologically benign and mastectomy in histologically malignant tumors are advised, but no final decision could be reached. It is proposed to restrict ther term cystosarcoma phyllodes to histologically malignant tumors and use the term fibroadenoma phyllodes in instances of histologically benign tumors.", "contents": "Clinical course of cystosarcoma phyllodes related to histologic appearance. A series of 17 females having cystosarcoma phyllodes underwent surgical treatment. The subsequent clinical course was observed periodically. Twelve patients had originally histologically benign tumors. Six patients had a recurrence, and of these, malignant characteristics developed in four instances. Five patients had originally histologically malignant tumors. Recurrences were encountered in four. Five patients died from a generalized spread of the tumor. Three of these patients had originally histologically benign tumors, in which malignant features of the recurrent tumor subsequently developed. The surgical treatment ranged from local excision to simple mastectomy with additional roentgenotherapy in three. Neither procedure prevented a recurrence from the original tumor, whether benign or malignant. Poor correlation exists between biologic behavior and histologic appearance of cystosarcoma phyllodes, independent of the surgical procedure. Wide local excision in histologically benign and mastectomy in histologically malignant tumors are advised, but no final decision could be reached. It is proposed to restrict ther term cystosarcoma phyllodes to histologically malignant tumors and use the term fibroadenoma phyllodes in instances of histologically benign tumors."} {"id": "PMID:165587", "title": "Effects of dibutyryl cyclic AMP on sinus rate and atrial contractile force in the isolated atrium of the dog.", "content": "In blood-perfused isolated canine atrium preparations, single injections of dibutyryl cyclic AMP at a dose range of 1 to 30 mg were made into the cannulated sinus node artery. At doses above 3 mg, dibutyryl cyclic AMP induced a biphasic chronotropic and inotropic response; there was a slight and rapid negative chronotropic and inotropic response, followed by a long-lasting positive chronotropic and inotropic response. The induction of the positive effects was slow, and it took 4 to 8 min to reach a maximum response. These effects continued 20 to 60 min. The ratios of the positive inotropic effect/positive chronotropic effect were very similar to those induced by norepinephrine. In this study, it was confirmed that a large dose of dibutyryl cyclic AMP induced a positive chronotropic and inotropic effect on the canine atrium, and the possibility was discussed that cyclic AMP may be involved in the effects of beta-adrenergic amines on the pacemaker and contractile process of the heart.", "contents": "Effects of dibutyryl cyclic AMP on sinus rate and atrial contractile force in the isolated atrium of the dog. In blood-perfused isolated canine atrium preparations, single injections of dibutyryl cyclic AMP at a dose range of 1 to 30 mg were made into the cannulated sinus node artery. At doses above 3 mg, dibutyryl cyclic AMP induced a biphasic chronotropic and inotropic response; there was a slight and rapid negative chronotropic and inotropic response, followed by a long-lasting positive chronotropic and inotropic response. The induction of the positive effects was slow, and it took 4 to 8 min to reach a maximum response. These effects continued 20 to 60 min. The ratios of the positive inotropic effect/positive chronotropic effect were very similar to those induced by norepinephrine. In this study, it was confirmed that a large dose of dibutyryl cyclic AMP induced a positive chronotropic and inotropic effect on the canine atrium, and the possibility was discussed that cyclic AMP may be involved in the effects of beta-adrenergic amines on the pacemaker and contractile process of the heart."} {"id": "PMID:165588", "title": "The sarcoma arising in giloblastoma: clinico-pathological report of two cases.", "content": "Two cases of primary brain tumor composed of an admixture of sarcomatous and gliomatous tissues are reported together with their clinical courses and neurosurgical examination. There is no difference in clinical course nor in the result of examination between the usual glioblastoma multiforme and these admixture tumor. The histological examination at the surgical biopsy and autopsy suggested that enoplastic change of the sarcomatous element occurs markedly on hyperplastic blood vessels in the glioblastoma multiforme. The neoplastic change observed on hyperplastic blood vessels is not affected by radiation therapy.", "contents": "The sarcoma arising in giloblastoma: clinico-pathological report of two cases. Two cases of primary brain tumor composed of an admixture of sarcomatous and gliomatous tissues are reported together with their clinical courses and neurosurgical examination. There is no difference in clinical course nor in the result of examination between the usual glioblastoma multiforme and these admixture tumor. The histological examination at the surgical biopsy and autopsy suggested that enoplastic change of the sarcomatous element occurs markedly on hyperplastic blood vessels in the glioblastoma multiforme. The neoplastic change observed on hyperplastic blood vessels is not affected by radiation therapy."} {"id": "PMID:165589", "title": "Responses to exogenous dibutyryl adenosine 3',5'-monophosphate of cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs.", "content": "Changes in the cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs were observed, using the non-cannulating electromagnetic flow meter. Dibutyryl cyclic-AMP, 5 mg/kg body weight, was given intravenously and the following results were obtained: 1) Dibutyryl cyclic-AMP increased the stroke volume and the cardiac output, and slightly increased the heart rate. These effects appeared 3 to 5 min after administration of dibutyryl cyclic-AMP. 2) The mean systemic blood pressure as well as the central venous pressure fell slightly. 3) The renal and the superior mesenteric artery blood flow increased markedly, but the carotid artery blood flow did not change. 4) Distribution of the cardiac output to the renal and superior mesenteric arteries did not change but distribution to the carotid artery decreased. 5) Total peripheral resistance, renal artery vascular resistance and superior mesenteric artery vascular resistance decreased, and carotid artery vascular resistance decreased slightly. 6) The cardiac output and blood flow were enhanced by aminophylline (3 mg/kg), and were not blocked by propranolol (0.3 mg/kg).", "contents": "Responses to exogenous dibutyryl adenosine 3',5'-monophosphate of cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs. Changes in the cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs were observed, using the non-cannulating electromagnetic flow meter. Dibutyryl cyclic-AMP, 5 mg/kg body weight, was given intravenously and the following results were obtained: 1) Dibutyryl cyclic-AMP increased the stroke volume and the cardiac output, and slightly increased the heart rate. These effects appeared 3 to 5 min after administration of dibutyryl cyclic-AMP. 2) The mean systemic blood pressure as well as the central venous pressure fell slightly. 3) The renal and the superior mesenteric artery blood flow increased markedly, but the carotid artery blood flow did not change. 4) Distribution of the cardiac output to the renal and superior mesenteric arteries did not change but distribution to the carotid artery decreased. 5) Total peripheral resistance, renal artery vascular resistance and superior mesenteric artery vascular resistance decreased, and carotid artery vascular resistance decreased slightly. 6) The cardiac output and blood flow were enhanced by aminophylline (3 mg/kg), and were not blocked by propranolol (0.3 mg/kg)."} {"id": "PMID:165594", "title": "Effects of intratracheal instillation of dactinomycin on pulmonary edema and phosphatase activity of the lung lavage fluid in rats.", "content": "Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent. Severity of lung damage due to act. D was dose- and almost age-related. Maximal intensity of pulmonary edema was reached on the 3rd day following administration and remained constant for 14 days. Histopathological studies revealed confluent edema of the entire lung. Pretreatment with act D induced tolerance to an LD100 edematogenic dose of thiourea. The effects of i.t. instillation of act. D appear to be localized in the pulmonary tissue. Lung lavage fluid collected from drug-treated rats had higher acid and alkaline phosphatase activities, higher protein content and more leukocyte infiltration than that of control.", "contents": "Effects of intratracheal instillation of dactinomycin on pulmonary edema and phosphatase activity of the lung lavage fluid in rats. Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent. Severity of lung damage due to act. D was dose- and almost age-related. Maximal intensity of pulmonary edema was reached on the 3rd day following administration and remained constant for 14 days. Histopathological studies revealed confluent edema of the entire lung. Pretreatment with act D induced tolerance to an LD100 edematogenic dose of thiourea. The effects of i.t. instillation of act. D appear to be localized in the pulmonary tissue. Lung lavage fluid collected from drug-treated rats had higher acid and alkaline phosphatase activities, higher protein content and more leukocyte infiltration than that of control."} {"id": "PMID:165595", "title": "Metabolism of 4-14 C-progesterone in the adult female chimpanzee.", "content": "The metabolism of 4- 14-C-progesterone was studied in two adult female chimpanzees (Pan troglodytes). After intravenous injection of 4- 14-C-progesterone, urine was collected for 5 days. The urinary conjugates were hydrolyzed with Glusulase and the extracts purified by chromatography on silica gel, paper and alumina and then crystallized to constant specific activity with or without carrier steroid. The major metabolite in both experiments was pregnanediol which accounted for 39.8% and 49.5% of the recovered dose respectively. Pregnanolone (0.6% and 2.1%) and pregnanetriol (0.1% and 1.5%) were also isolated in smaller quantities. These data suggest that the pattern of progesterone metabolism in the chimpanzee is similar to that of man in that pregnanediol is the major metabolite whereas androsterone is not.", "contents": "Metabolism of 4-14 C-progesterone in the adult female chimpanzee. The metabolism of 4- 14-C-progesterone was studied in two adult female chimpanzees (Pan troglodytes). After intravenous injection of 4- 14-C-progesterone, urine was collected for 5 days. The urinary conjugates were hydrolyzed with Glusulase and the extracts purified by chromatography on silica gel, paper and alumina and then crystallized to constant specific activity with or without carrier steroid. The major metabolite in both experiments was pregnanediol which accounted for 39.8% and 49.5% of the recovered dose respectively. Pregnanolone (0.6% and 2.1%) and pregnanetriol (0.1% and 1.5%) were also isolated in smaller quantities. These data suggest that the pattern of progesterone metabolism in the chimpanzee is similar to that of man in that pregnanediol is the major metabolite whereas androsterone is not."} {"id": "PMID:165596", "title": "Specific progesterone receptors in human breast cancer.", "content": "We have identified a specific progesterone receptor in 11 of 33 human breast cancer cytosols. Since progesterone itself binds to glucocorticoid receptor, to corticosteroid binding globulin (CBG), and to nonspecific components as well as to its own receptor, we have used a synthetic progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), whose binding specificity is restricted to progesterone receptor. Bound R5020 sediments at 8 S in sucrose gradients; binding is competed by excess unlabeled R5020 or progesterone. The receptor is distinct from glucocorticoid receptor and CBG as determined by competition studies using dexamethasone and hydrocortisone. The dissociation constant for R5020 obtained by Scatchard analysis of dextran-coated charcoal assays is approximately 2 times 10- minus 9 M.", "contents": "Specific progesterone receptors in human breast cancer. We have identified a specific progesterone receptor in 11 of 33 human breast cancer cytosols. Since progesterone itself binds to glucocorticoid receptor, to corticosteroid binding globulin (CBG), and to nonspecific components as well as to its own receptor, we have used a synthetic progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), whose binding specificity is restricted to progesterone receptor. Bound R5020 sediments at 8 S in sucrose gradients; binding is competed by excess unlabeled R5020 or progesterone. The receptor is distinct from glucocorticoid receptor and CBG as determined by competition studies using dexamethasone and hydrocortisone. The dissociation constant for R5020 obtained by Scatchard analysis of dextran-coated charcoal assays is approximately 2 times 10- minus 9 M."} {"id": "PMID:165597", "title": "Androgen binding to cytosol prepared from epididymides of sexually mature castrated rabbits: evidence for a cytoplasmic receptor.", "content": "The presence of androgen-binding activity in cytosol prepared from the major anatomical segments (caput, corpus, and cauda) of the epididymis of castrated sexually mature rabbits has been demonstrated. A portion of this binding activity is likely to be the epididymal androgen receptor. When epididymal cytosol from adult castrated rabbits is analyzed on low-ionic strength (0.01 MKCl) sucrose gradients, two peaks of macromolecular binding could be detected, one congruent to 4.6S and one congruent to 8S. On gradients containing 1.0 M KCl, only one sedimenting form congruent to 4.6S could be demonstrated, suggesting that the 8S component is composed of aggregates. If cytosol was preincubated with labeled androgen, followed by an incubation with unlabeled androgen, and subsequently analyzed for binding on low-ionic strength gradients, only the congruent to 8S peak could be detected, indicating that most of the binding in the congruent to 4.6S region was rapidly dissociable. This suggests that binding in this region was to moieties other than receptor. Since androgen binding proteins (ABP) of testicular origin would have been cleared from the epididymis at the timepoints that we concentrated on for most of these studies, the 4.6S binding probably represents the association of androgen with plasma testosterone binding globulin (TeBG). The binding of androgen to the receptor can be inhibited by cyproterone, while this antiandrogen does not inhibit binding to either ABP or TeBG at the concentration used.", "contents": "Androgen binding to cytosol prepared from epididymides of sexually mature castrated rabbits: evidence for a cytoplasmic receptor. The presence of androgen-binding activity in cytosol prepared from the major anatomical segments (caput, corpus, and cauda) of the epididymis of castrated sexually mature rabbits has been demonstrated. A portion of this binding activity is likely to be the epididymal androgen receptor. When epididymal cytosol from adult castrated rabbits is analyzed on low-ionic strength (0.01 MKCl) sucrose gradients, two peaks of macromolecular binding could be detected, one congruent to 4.6S and one congruent to 8S. On gradients containing 1.0 M KCl, only one sedimenting form congruent to 4.6S could be demonstrated, suggesting that the 8S component is composed of aggregates. If cytosol was preincubated with labeled androgen, followed by an incubation with unlabeled androgen, and subsequently analyzed for binding on low-ionic strength gradients, only the congruent to 8S peak could be detected, indicating that most of the binding in the congruent to 4.6S region was rapidly dissociable. This suggests that binding in this region was to moieties other than receptor. Since androgen binding proteins (ABP) of testicular origin would have been cleared from the epididymis at the timepoints that we concentrated on for most of these studies, the 4.6S binding probably represents the association of androgen with plasma testosterone binding globulin (TeBG). The binding of androgen to the receptor can be inhibited by cyproterone, while this antiandrogen does not inhibit binding to either ABP or TeBG at the concentration used."} {"id": "PMID:165598", "title": "Androgen receptor in human skin fibroblasts. Characterization of a specific 17beta-hydroxy-5alpha-androstan-3-one-protein complex in cell sonicates and nuclei.", "content": "Cultured human skin fibroblasts were shown to contain an androgen binding activity (receptor) which was heat-labile and destroyed by trypsin. Specific binding was seen after incubations of these cells with 1,2-3-H-testosterone, 1,2-3-H17beta-hydroxy-5alpha-androstan-3-one (dihydrotestosterone, DHT) and 1,2-3-H-5alpha-androstane-3alpha, 17beta-diol. This receptor had a high affinity (Kd=0,2-1.6 nM) and a high degree of specificity for DHT. It was measured as a 3-H-DHT-protein complex by gel filtration chromatography using a method which distinguishes specific from nonspecific binding. Receptor activity was distributed about equally between nuclear and extranuclear components at all times studied and was present in both compartments when cell incubations were carried out at 4 degrees and 37 degrees. Saturation analysis indicated that there were 1250-18,600 binding sites per whole cell. By sucrose gradient centrifugation the receptor had a sedimentation coefficient (S20,w) of about 4. Cells grown for 8 days without serum in the medium maintained the same levels of 3-H-DHT binding. Within 15 hours puromycin (20 mug/ml) in serum-free medium caused a 40-60 percent decrease in binding for the same cell lines. Although the highest levels of 3-H-DHT binding were observed in fibroblasts from newborn foreskin, appreciable cytosol and nuclear binding were seen in cells from forearm, neck and abdominal skin. Receptor activity was stable during prolonged culture. Fibroblasts from several skin sites from patients with the androgen insensitivity syndrome (testicular feminization) had no detectable specific DHT binding. In this study it was demonstrated that skin fibroblasts can rapidly convert testosterone to its active form, DHT, bind DHT to a specific receptor protein and transport this complex to their nuclei. Therefore this may prove to be a convenient system for studying androgen action in vitro.", "contents": "Androgen receptor in human skin fibroblasts. Characterization of a specific 17beta-hydroxy-5alpha-androstan-3-one-protein complex in cell sonicates and nuclei. Cultured human skin fibroblasts were shown to contain an androgen binding activity (receptor) which was heat-labile and destroyed by trypsin. Specific binding was seen after incubations of these cells with 1,2-3-H-testosterone, 1,2-3-H17beta-hydroxy-5alpha-androstan-3-one (dihydrotestosterone, DHT) and 1,2-3-H-5alpha-androstane-3alpha, 17beta-diol. This receptor had a high affinity (Kd=0,2-1.6 nM) and a high degree of specificity for DHT. It was measured as a 3-H-DHT-protein complex by gel filtration chromatography using a method which distinguishes specific from nonspecific binding. Receptor activity was distributed about equally between nuclear and extranuclear components at all times studied and was present in both compartments when cell incubations were carried out at 4 degrees and 37 degrees. Saturation analysis indicated that there were 1250-18,600 binding sites per whole cell. By sucrose gradient centrifugation the receptor had a sedimentation coefficient (S20,w) of about 4. Cells grown for 8 days without serum in the medium maintained the same levels of 3-H-DHT binding. Within 15 hours puromycin (20 mug/ml) in serum-free medium caused a 40-60 percent decrease in binding for the same cell lines. Although the highest levels of 3-H-DHT binding were observed in fibroblasts from newborn foreskin, appreciable cytosol and nuclear binding were seen in cells from forearm, neck and abdominal skin. Receptor activity was stable during prolonged culture. Fibroblasts from several skin sites from patients with the androgen insensitivity syndrome (testicular feminization) had no detectable specific DHT binding. In this study it was demonstrated that skin fibroblasts can rapidly convert testosterone to its active form, DHT, bind DHT to a specific receptor protein and transport this complex to their nuclei. Therefore this may prove to be a convenient system for studying androgen action in vitro."} {"id": "PMID:165607", "title": "Accessory phallic urethra in female pseudohermaphrodite.", "content": "The eighth case of a female pseudohermaphrodite with hypertrophy of the clitoris, a perineal and complete accessory phallic urethra, but without adrenal hyperplasia, is reported. The etiology of this syndrome and the rationale of its treatment are discussed and the literature reviewed.", "contents": "Accessory phallic urethra in female pseudohermaphrodite. The eighth case of a female pseudohermaphrodite with hypertrophy of the clitoris, a perineal and complete accessory phallic urethra, but without adrenal hyperplasia, is reported. The etiology of this syndrome and the rationale of its treatment are discussed and the literature reviewed."} {"id": "PMID:165609", "title": "An experimental inactivated vaccine against bluetongue.", "content": "Bluetongue virus grown in BHK cells was shown to be inactivated in concentrations of betapropiolactone (BPL) higher than 0-15 per cent. When the virus, inactivated with 0-2 per cent BPL and prepared as a double emulsion vaccine, was injected into Cypriot sheep, no untoward reactions were observed and neutralising antibodies developed. The antibody titre reached a high level and persisted for at least a year. After re-vaccination, a secondary response was observed. A bivalent vaccine elicited a response to both virus types incorporated. The possibilities of using a polyvalent inactivated vaccine are discussed.", "contents": "An experimental inactivated vaccine against bluetongue. Bluetongue virus grown in BHK cells was shown to be inactivated in concentrations of betapropiolactone (BPL) higher than 0-15 per cent. When the virus, inactivated with 0-2 per cent BPL and prepared as a double emulsion vaccine, was injected into Cypriot sheep, no untoward reactions were observed and neutralising antibodies developed. The antibody titre reached a high level and persisted for at least a year. After re-vaccination, a secondary response was observed. A bivalent vaccine elicited a response to both virus types incorporated. The possibilities of using a polyvalent inactivated vaccine are discussed."} {"id": "PMID:165605", "title": "[Cytogenetic mechanisms in the pathogenesis of malignant neoplasms].", "content": "Malignant tumors and pre-cancer processes are characterized by a high proliferative activity of cells, high chromosome variability and extremely high genome variability which is 10 times, as high as that in non-tumor actively proliferating tissues. A clear positive correlation is found between the cell division rate and the level of chromosome variability.", "contents": "[Cytogenetic mechanisms in the pathogenesis of malignant neoplasms]. Malignant tumors and pre-cancer processes are characterized by a high proliferative activity of cells, high chromosome variability and extremely high genome variability which is 10 times, as high as that in non-tumor actively proliferating tissues. A clear positive correlation is found between the cell division rate and the level of chromosome variability."} {"id": "PMID:165610", "title": "\"Dog pox\": some clinical aspects of an eruptive condition of certain mucous surfaces in dogs.", "content": "An eruptive condition seen on certain mucous membranes of dogs occurs frequently but often asymptomatically. Lesions have been found to be present in over 60 percent of male dogs. The infection is probably due to a canine herpes virus and has been termed conveniently but inaccurately \"dog pox\". In many cases lesions are present without observable clinical signs but severe irritation, especially related to lesions in the lower bowel, can give rise to marked symptoms which may be confused with abnormality of the para-anal sacs, or to chronic diarrhoea of a type suggestive of colitis. The incidence, sites of infection and possible syndromes which may be ascribed to the condition are briefly discussed on a clinical basis only.", "contents": "\"Dog pox\": some clinical aspects of an eruptive condition of certain mucous surfaces in dogs. An eruptive condition seen on certain mucous membranes of dogs occurs frequently but often asymptomatically. Lesions have been found to be present in over 60 percent of male dogs. The infection is probably due to a canine herpes virus and has been termed conveniently but inaccurately \"dog pox\". In many cases lesions are present without observable clinical signs but severe irritation, especially related to lesions in the lower bowel, can give rise to marked symptoms which may be confused with abnormality of the para-anal sacs, or to chronic diarrhoea of a type suggestive of colitis. The incidence, sites of infection and possible syndromes which may be ascribed to the condition are briefly discussed on a clinical basis only."} {"id": "PMID:165612", "title": "[Plaque characteristics of herpes mamillitis virus (HMV)].", "content": "The virus of the bovine herpes mammillitis (VHM) produces a homogeneous plaque population. The plaques are either round or have the form of a slightly irregular circle, cized 2--3 mm in diameter, with a semitranslucent center. The microscopic examination of paticular plaques has revealed a necrotic center composed of destroyed cells, and in cases where the gross examination gives a clearly defined ontour there is a band of both normal and destroyed cells. No morphologic differences have been established in plaque formation so far as local strains KOS/H-ovo and DZS and the reference strain TVA are concerned. It has been found that the number of the plaques formed is directly proportional to the concentration of the inoculated virus. The preciseness and specificity of the plaque reduction test has been demonstrated as well. The comparative testing of hydrolysed starch, agarose, agar, and carboxylmethylcellulose for the plaque study of VHM has shown that best results are obtained with the use of starch and agarose, no morphologic variation being established among plaques overlaid with the four tested substances.", "contents": "[Plaque characteristics of herpes mamillitis virus (HMV)]. The virus of the bovine herpes mammillitis (VHM) produces a homogeneous plaque population. The plaques are either round or have the form of a slightly irregular circle, cized 2--3 mm in diameter, with a semitranslucent center. The microscopic examination of paticular plaques has revealed a necrotic center composed of destroyed cells, and in cases where the gross examination gives a clearly defined ontour there is a band of both normal and destroyed cells. No morphologic differences have been established in plaque formation so far as local strains KOS/H-ovo and DZS and the reference strain TVA are concerned. It has been found that the number of the plaques formed is directly proportional to the concentration of the inoculated virus. The preciseness and specificity of the plaque reduction test has been demonstrated as well. The comparative testing of hydrolysed starch, agarose, agar, and carboxylmethylcellulose for the plaque study of VHM has shown that best results are obtained with the use of starch and agarose, no morphologic variation being established among plaques overlaid with the four tested substances."} {"id": "PMID:165606", "title": "[Electron microscopic study of Mikulicz's cells].", "content": "The results are presented of the electron-microscopic examination of the main element of scleroma granulomatous tissue - the Mikulicz cells. New data on the shape and structure of their nuclei as well as on the presence of electron-dense bodies in their cytoplasma are given.", "contents": "[Electron microscopic study of Mikulicz's cells]. The results are presented of the electron-microscopic examination of the main element of scleroma granulomatous tissue - the Mikulicz cells. New data on the shape and structure of their nuclei as well as on the presence of electron-dense bodies in their cytoplasma are given."} {"id": "PMID:165611", "title": "[The effect of microbial contemination of the air on metabolic indices in broiler chickens].", "content": "Trials were carried out with two groups of birds, White Plymouth times Cornish crosses. A third, control group of birds was also involved in the experiments, reared by the same technology. The only difference consisted in that the air in the premise of the test birds had a lower microbial content which, during the experiments was 2 to 5 times lower than that in the air of the controls. It was found that under the effect of the higher microbial content the blood serum protein drops like the protein content of the liver and heart musculature, the content of free amino acids rises, the amount of triptophane lowers, and the activity of GOT and GPT is enhanced. The birds of the control group show higher enzyme activity so far as the glucose-6-phosphatase of the liver is concerned, lower glycogen content of the liver, and lower blood concentration of glucose. By the end of the trials the broilers of the control group were 50 gr less heavy than the lest birds.", "contents": "[The effect of microbial contemination of the air on metabolic indices in broiler chickens]. Trials were carried out with two groups of birds, White Plymouth times Cornish crosses. A third, control group of birds was also involved in the experiments, reared by the same technology. The only difference consisted in that the air in the premise of the test birds had a lower microbial content which, during the experiments was 2 to 5 times lower than that in the air of the controls. It was found that under the effect of the higher microbial content the blood serum protein drops like the protein content of the liver and heart musculature, the content of free amino acids rises, the amount of triptophane lowers, and the activity of GOT and GPT is enhanced. The birds of the control group show higher enzyme activity so far as the glucose-6-phosphatase of the liver is concerned, lower glycogen content of the liver, and lower blood concentration of glucose. By the end of the trials the broilers of the control group were 50 gr less heavy than the lest birds."} {"id": "PMID:165613", "title": "[Concurrent vulvovaginitis, respiratory syndrome and keratoconjunctivitis in calves].", "content": "Studied was a disease course in calves caused by the IBR/IPV virus with symptoms characteristic of vulvovaginitis, respiratory distrubances and keratoconjunctivitis. Concurrent infections of such type were observed primarily in several-month-old calves (aged from 6--7 weeks to 6 months). In older calves (aged 1--2 years) vulvovaginitis predominated, it being more rarely associated with changes typical of pneumonia, and, as an exception accompanied by keratoconjunctivitis. Dairy cows exhibited predominatly the chronic form of vulvovaginitis. Isolated were 16 strains of the IBR/IPV virus showing properties analogous of those of the standard Oxford strain. Demonstrated were specific IBR/IPV antibodies in calves, cows and bulls (from 24.5 up to 50 per cent). The problem is discussed of the correlation between sterility in cows showing the presence of the IBR/IPV virus and the symptoms of vulvovaginits as well as the presence of hypospermia and balanoposthitis in bulls harbouring the virus infection.", "contents": "[Concurrent vulvovaginitis, respiratory syndrome and keratoconjunctivitis in calves]. Studied was a disease course in calves caused by the IBR/IPV virus with symptoms characteristic of vulvovaginitis, respiratory distrubances and keratoconjunctivitis. Concurrent infections of such type were observed primarily in several-month-old calves (aged from 6--7 weeks to 6 months). In older calves (aged 1--2 years) vulvovaginitis predominated, it being more rarely associated with changes typical of pneumonia, and, as an exception accompanied by keratoconjunctivitis. Dairy cows exhibited predominatly the chronic form of vulvovaginitis. Isolated were 16 strains of the IBR/IPV virus showing properties analogous of those of the standard Oxford strain. Demonstrated were specific IBR/IPV antibodies in calves, cows and bulls (from 24.5 up to 50 per cent). The problem is discussed of the correlation between sterility in cows showing the presence of the IBR/IPV virus and the symptoms of vulvovaginits as well as the presence of hypospermia and balanoposthitis in bulls harbouring the virus infection."} {"id": "PMID:165614", "title": "[Histochemical and histoenzymatic study of experimental myocardial infarction in the rat by temporary and permanent ligation of the left coronary artery (author's transl)].", "content": "The evolution of experimental myocardial infarction in the Rat with or without revascularization has been studied histochemically and histoenzymatically in 56 animals sacrified after 1, 6, 12, 24, 48 hrs and 7 days. Following permanent ischemis (14 animals), there appeared an extended transversal infarction marked by the complete disappearance of all phosphorylase activity (P-ase) after the first hour. During the first 6 hrs, changes appeared in succinodeshydrogenase (SHD) and cytochrome oxydase (Cyt-Ox). Glucose-6-phosphodeshydrogenase (G6PDH) presisted until lysis of the necrotic focus. It was possible to define a perinecrotic marginal area in which Pase activity is absent and SDH is granular \"G3 in nature, characterized by continuous remodeling in the first 48 hrs. Following temporary ischemia (42 animals) the evolution was marked by rapid tissue reactions and early regression of the marginal zones. After 48 hrs and 7 days of survival, the planimetric evaluation of the infarcted area shows a definite reduction in the size of the infarctus in 50% of cases following removal of the ligature after 6 hrs, and in 66% of cases following removal of the ligature after 1 hr. It would appear probable that the revitalization of certain myocardial areas may extend from the marginal zones as is suggested by the reappearance in these zones several hrs after revascularization of P-ase and SDH activity. On the other hand, it is also true that the early restoration of blood flow does not always prevent the occurrence of an extended infarction. Certain recent observations have shown microcirculatory changes which are secondary to anoxia and should be studied further.", "contents": "[Histochemical and histoenzymatic study of experimental myocardial infarction in the rat by temporary and permanent ligation of the left coronary artery (author's transl)]. The evolution of experimental myocardial infarction in the Rat with or without revascularization has been studied histochemically and histoenzymatically in 56 animals sacrified after 1, 6, 12, 24, 48 hrs and 7 days. Following permanent ischemis (14 animals), there appeared an extended transversal infarction marked by the complete disappearance of all phosphorylase activity (P-ase) after the first hour. During the first 6 hrs, changes appeared in succinodeshydrogenase (SHD) and cytochrome oxydase (Cyt-Ox). Glucose-6-phosphodeshydrogenase (G6PDH) presisted until lysis of the necrotic focus. It was possible to define a perinecrotic marginal area in which Pase activity is absent and SDH is granular \"G3 in nature, characterized by continuous remodeling in the first 48 hrs. Following temporary ischemia (42 animals) the evolution was marked by rapid tissue reactions and early regression of the marginal zones. After 48 hrs and 7 days of survival, the planimetric evaluation of the infarcted area shows a definite reduction in the size of the infarctus in 50% of cases following removal of the ligature after 6 hrs, and in 66% of cases following removal of the ligature after 1 hr. It would appear probable that the revitalization of certain myocardial areas may extend from the marginal zones as is suggested by the reappearance in these zones several hrs after revascularization of P-ase and SDH activity. On the other hand, it is also true that the early restoration of blood flow does not always prevent the occurrence of an extended infarction. Certain recent observations have shown microcirculatory changes which are secondary to anoxia and should be studied further."} {"id": "PMID:165615", "title": "The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism.", "content": "In a newborn severe persistent hypoglycemia due to an insulin-producing tumorous proliferation of pancreatic islet cells (insulinoma) was observed. The insulinoma showed the histologic pattern of focal adenomatosis of islet cells. According to the present literature the focal proliferation of islet cell complexes seems to be a frequent and particular feature of insulinomas in the newborn. Differential islet cell staining identified 80%-90% of the proliferated islet cells as B cells. 10%-20% of the cells were found to be A or D cells. Ultrastructurally the majority of the proliferated islet cells were well differentiated B cells. The remaining cells represented either A or D cells or a fourth islet cell type with small spheric granules. Electronmicrscopic evidence of transitions between differentiated islet cells, particularly B cells, and the fourth islet cell type suggests that the fourth islet cell type might represent a precursor cell within the APUD-cell system.", "contents": "The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism. In a newborn severe persistent hypoglycemia due to an insulin-producing tumorous proliferation of pancreatic islet cells (insulinoma) was observed. The insulinoma showed the histologic pattern of focal adenomatosis of islet cells. According to the present literature the focal proliferation of islet cell complexes seems to be a frequent and particular feature of insulinomas in the newborn. Differential islet cell staining identified 80%-90% of the proliferated islet cells as B cells. 10%-20% of the cells were found to be A or D cells. Ultrastructurally the majority of the proliferated islet cells were well differentiated B cells. The remaining cells represented either A or D cells or a fourth islet cell type with small spheric granules. Electronmicrscopic evidence of transitions between differentiated islet cells, particularly B cells, and the fourth islet cell type suggests that the fourth islet cell type might represent a precursor cell within the APUD-cell system."} {"id": "PMID:165632", "title": "[Determination of individual sensitivity of gastric cancer to 5-fluorouracil by tumor tissue respiratory and glycolytic indices].", "content": "Eighty one patients were studied for individual susceptibility of gastric tumors to 5-FU as evidenced by endogenic respiration and glycolysis of fresh tumor sections, the main criterion being the suppressed respiration, the accessory one inhibition of glycolysis. Three groups of tumors were differentiated: susceptible (25.9%), slightly susceptible (28.4%) and unsusceptible (45.7%) to 5-fluoruracil. Mostly adenocarcinomas were found in a group of susceptible tumors, scirrhous and colloid cancers -- in an unsusceptible group. A correlation outlined between the results of determining susceptibility in vitro and clinical data enabled to recommend the method of determining susceptibility to 5-FU for clinical application.", "contents": "[Determination of individual sensitivity of gastric cancer to 5-fluorouracil by tumor tissue respiratory and glycolytic indices]. Eighty one patients were studied for individual susceptibility of gastric tumors to 5-FU as evidenced by endogenic respiration and glycolysis of fresh tumor sections, the main criterion being the suppressed respiration, the accessory one inhibition of glycolysis. Three groups of tumors were differentiated: susceptible (25.9%), slightly susceptible (28.4%) and unsusceptible (45.7%) to 5-fluoruracil. Mostly adenocarcinomas were found in a group of susceptible tumors, scirrhous and colloid cancers -- in an unsusceptible group. A correlation outlined between the results of determining susceptibility in vitro and clinical data enabled to recommend the method of determining susceptibility to 5-FU for clinical application."} {"id": "PMID:165633", "title": "[The clinical picture and diagnosis of mechanical jaundice during tumor growth].", "content": "Studies on the clinical course of the lesion in 525 patients with malignant tumors of the bilio-pancreato-duodenal system organs have evidenced that jaundice is not an early sign of the affection. In developed jaundice it is rational to differentiate two main diagnostic stages: presurgical which main task is differentiation between mechanic jaundice and hepatocellular jaundice, the greatest importance being attached to clinical investigation of serum enzymes and clinical data. The second main diagnostic stage is an operation during which all feasible methods of ultimate diagnosis should be employed, including direct cholangiography and urgent microscopy of a tumor.", "contents": "[The clinical picture and diagnosis of mechanical jaundice during tumor growth]. Studies on the clinical course of the lesion in 525 patients with malignant tumors of the bilio-pancreato-duodenal system organs have evidenced that jaundice is not an early sign of the affection. In developed jaundice it is rational to differentiate two main diagnostic stages: presurgical which main task is differentiation between mechanic jaundice and hepatocellular jaundice, the greatest importance being attached to clinical investigation of serum enzymes and clinical data. The second main diagnostic stage is an operation during which all feasible methods of ultimate diagnosis should be employed, including direct cholangiography and urgent microscopy of a tumor."} {"id": "PMID:165635", "title": "[The effectiveness of treatment for breast cancer patients].", "content": "The study of late results of treatment in 1166 patients with breast cancer permitted to find the percentage of a 5-year survival to be equal to 55.58, 37.93% of patients survived for 10 years, 28.25% -- for 15 years. In the first stage a 5-year survival was 87.20%, while in the second and third -- 57.7% and 31.56% of patients survived for 5 years, accordingly. The modern methods of radiotherapy (radiosurgical method, interstitial gamma therapy with Au-198 granules, distance grammatherapy on the machine LUCH) enhanced the efficacy of therapeutic measures in patients with widespread breast cancer. A complex diagnosis -- cytology, non-contrast mammography and mathematical analysis by means of a computer contributes to recognition of early forms of breast cancer.", "contents": "[The effectiveness of treatment for breast cancer patients]. The study of late results of treatment in 1166 patients with breast cancer permitted to find the percentage of a 5-year survival to be equal to 55.58, 37.93% of patients survived for 10 years, 28.25% -- for 15 years. In the first stage a 5-year survival was 87.20%, while in the second and third -- 57.7% and 31.56% of patients survived for 5 years, accordingly. The modern methods of radiotherapy (radiosurgical method, interstitial gamma therapy with Au-198 granules, distance grammatherapy on the machine LUCH) enhanced the efficacy of therapeutic measures in patients with widespread breast cancer. A complex diagnosis -- cytology, non-contrast mammography and mathematical analysis by means of a computer contributes to recognition of early forms of breast cancer."} {"id": "PMID:165636", "title": "[Surgical treatment of breast cancer patients (according to material from the Rovno, Novgorod, Zvenigorod, Murmansk and Volynsk oncologic dispensaries].", "content": "A retrospective analysis of the survival in 230 patients with breast cancer, stage T1N0M0, subjected to mastectomy is presented. The results of treatment are compared with the survival of 62 patients, in whom economic resections were performed (segmental resection, routine mastectomy). In both groups of patients late results of treatment in stage T1N0M0 practically coincided. It was found that about 20% of nonpulpable axillary lymph nodes proved to be involved in metastases. Due to this, it is recommended to perform economic operations simultaneously with surgical dissection of axillary lymph nodes en bloc with a tumor.", "contents": "[Surgical treatment of breast cancer patients (according to material from the Rovno, Novgorod, Zvenigorod, Murmansk and Volynsk oncologic dispensaries]. A retrospective analysis of the survival in 230 patients with breast cancer, stage T1N0M0, subjected to mastectomy is presented. The results of treatment are compared with the survival of 62 patients, in whom economic resections were performed (segmental resection, routine mastectomy). In both groups of patients late results of treatment in stage T1N0M0 practically coincided. It was found that about 20% of nonpulpable axillary lymph nodes proved to be involved in metastases. Due to this, it is recommended to perform economic operations simultaneously with surgical dissection of axillary lymph nodes en bloc with a tumor."} {"id": "PMID:165638", "title": "Persistent or slow viral infections and related diseases.", "content": "The discovery of persistent transmissible agents by veterinarians has led to striking advances in the infectious cause of neuropathies of human beings. There is evidence for persisting infection in congenital rubella and the herpes group of viruses including cytomegalovirus infections. Hepatitis types A and B are candidates for inclusion in the category of persisting viral infections. The rubeola or measles virus is established as a persistent virus which causes elevated antibodies in the serum and cerebrospinal fluid of many patients with severe demyelinating disease such as subacute sclerosing panencephalitis and multiple sclerosis. Elevated antibodies against vaccinia virus have been found in the cerebrospinal fluid of some patients with multiple sclerosis and neuromyelitis optica, a rare form of multiple sclerosis.", "contents": "Persistent or slow viral infections and related diseases. The discovery of persistent transmissible agents by veterinarians has led to striking advances in the infectious cause of neuropathies of human beings. There is evidence for persisting infection in congenital rubella and the herpes group of viruses including cytomegalovirus infections. Hepatitis types A and B are candidates for inclusion in the category of persisting viral infections. The rubeola or measles virus is established as a persistent virus which causes elevated antibodies in the serum and cerebrospinal fluid of many patients with severe demyelinating disease such as subacute sclerosing panencephalitis and multiple sclerosis. Elevated antibodies against vaccinia virus have been found in the cerebrospinal fluid of some patients with multiple sclerosis and neuromyelitis optica, a rare form of multiple sclerosis."} {"id": "PMID:165641", "title": "[Sudden deafness and cytomegaly virus infection (author's transl)].", "content": "A 49-year old patient complained of sudden deafness in his right ear. With the exception of a rising titre level of the complement-fixing antibodies there were no positive findings for the cytomegaly virus. However, the eight-fold rise in the titre level after a latent period made it appear likely that the sudden deafness was caused by a cytomegaly virus infection. This assumption was also supported by the lack of vestibular symptoms, which, according to literature, is quite frequent in virus diseases of the inner ear. The usual therapy led to an improvement in the patient's hearing, which was also accompanied by a drop in the titre level of the antibodies. No prognosis can be made, since similar observations have not yet been recorded.", "contents": "[Sudden deafness and cytomegaly virus infection (author's transl)]. A 49-year old patient complained of sudden deafness in his right ear. With the exception of a rising titre level of the complement-fixing antibodies there were no positive findings for the cytomegaly virus. However, the eight-fold rise in the titre level after a latent period made it appear likely that the sudden deafness was caused by a cytomegaly virus infection. This assumption was also supported by the lack of vestibular symptoms, which, according to literature, is quite frequent in virus diseases of the inner ear. The usual therapy led to an improvement in the patient's hearing, which was also accompanied by a drop in the titre level of the antibodies. No prognosis can be made, since similar observations have not yet been recorded."} {"id": "PMID:165645", "title": "Cerebrospinal fluid concentration and urinary excretion of cyclic adenosine-3', 5'-monophosphate in various diseases of children.", "content": "Cerebrospinal fluid (CSF) concentration and urinary excretion of cyclic adenosine-3',5'-monophosphate(cAMP) were measured in children aged from 3 days to 15 years by the protein-binding method of Gilman (1970). The mean CSF cAMP concentration (22.4 plus or minus 0.6 (S.E.) nmol/l) of 24 \"healthy\" children tended to be lower (P less then 0.2) than that of adult patients who revealed no pathological findings on clinical examination. No difference in the results was foung between the sexes. High cAMP concentrations were found in CSF of children suffering from cerebellar glioma, hypothalamic precocious puberty, bacterial meningitis, or Cushing's disease. The urinary excretion of cAMP varied from 0.2 to 5.3 in \"healthy\" and from 1.3 to 7.6 mumol/24 hrs in diseased children. Two children with pheochromocytoma showed a striking decrease in the rate of urinary excretion of the nucleotide after surgical treatment.", "contents": "Cerebrospinal fluid concentration and urinary excretion of cyclic adenosine-3', 5'-monophosphate in various diseases of children. Cerebrospinal fluid (CSF) concentration and urinary excretion of cyclic adenosine-3',5'-monophosphate(cAMP) were measured in children aged from 3 days to 15 years by the protein-binding method of Gilman (1970). The mean CSF cAMP concentration (22.4 plus or minus 0.6 (S.E.) nmol/l) of 24 \"healthy\" children tended to be lower (P less then 0.2) than that of adult patients who revealed no pathological findings on clinical examination. No difference in the results was foung between the sexes. High cAMP concentrations were found in CSF of children suffering from cerebellar glioma, hypothalamic precocious puberty, bacterial meningitis, or Cushing's disease. The urinary excretion of cAMP varied from 0.2 to 5.3 in \"healthy\" and from 1.3 to 7.6 mumol/24 hrs in diseased children. Two children with pheochromocytoma showed a striking decrease in the rate of urinary excretion of the nucleotide after surgical treatment."} {"id": "PMID:165646", "title": "Pathogenic mechanisms not operating in Eimeria necatrix infections.", "content": "Having investigated certain aspects of Eimeria necatrix coccidiosis in chickens, workers of the Hannover Veterinary School postulated \"that death following a single inoculation of a large number of oocysts is due to an alarm reaction and not a specific pathogenic action of the parasites\". Because this hypothesis is somewhat revolutionary in its consept, several pieces of evidence on which it is based and several logical deductions which can be made from it have been examined. It has been confirmed that injection of chichens with cysteamine or 5-hydroxytryptamine 30 min before inoculation of the birds with a lethal dose of E. necatrix oocysts reduces subsequent mortality; the reason for this, however, appears not to be the neutralisation of the proposed shock reaction, but rather an inhibition of the excystation process, brought about indirectly through the host. Inoculation of chickens with a non-lethal dose of E. necatrix oocysts 30 min before inoculation with a lethal dose of oocysts was followed by increased mortality rather than the decreased mortality which the hypothesis would predict. Treatment of chickens with sulphadimidine starting 48 h after inoculation resulted in survival of the birds rather than death which would ensue if in fact mortality was due to a shock reaction irreversibly initiated at the time of inoculation. A direct effect of sulphadimidine on the parasite has been shown both in vivo and in vitro.", "contents": "Pathogenic mechanisms not operating in Eimeria necatrix infections. Having investigated certain aspects of Eimeria necatrix coccidiosis in chickens, workers of the Hannover Veterinary School postulated \"that death following a single inoculation of a large number of oocysts is due to an alarm reaction and not a specific pathogenic action of the parasites\". Because this hypothesis is somewhat revolutionary in its consept, several pieces of evidence on which it is based and several logical deductions which can be made from it have been examined. It has been confirmed that injection of chichens with cysteamine or 5-hydroxytryptamine 30 min before inoculation of the birds with a lethal dose of E. necatrix oocysts reduces subsequent mortality; the reason for this, however, appears not to be the neutralisation of the proposed shock reaction, but rather an inhibition of the excystation process, brought about indirectly through the host. Inoculation of chickens with a non-lethal dose of E. necatrix oocysts 30 min before inoculation with a lethal dose of oocysts was followed by increased mortality rather than the decreased mortality which the hypothesis would predict. Treatment of chickens with sulphadimidine starting 48 h after inoculation resulted in survival of the birds rather than death which would ensue if in fact mortality was due to a shock reaction irreversibly initiated at the time of inoculation. A direct effect of sulphadimidine on the parasite has been shown both in vivo and in vitro."} {"id": "PMID:165647", "title": "Alterations in cyclic necleotides in dogs after triiodothyronine.", "content": "The effects of triiodothyronine (T3) on plasma and tissue levels (liver, adipose tissue, muscle) of adenosine 3',5'-monophosphate (cyclic GMP) were determined in Mongrel dogs. Plasma cyclic AMP increased to a mean plateau value 165% greater than control values in response to a single intravenous injection of T3 (100-200 mug/kg body weight). This treatment resulted in no increase in plasma cyclic GMP. In liver, cyclic AMP concentration decreased 54%, while cyclic GMP increased 137%. Adipose tissue cyclic AMP levels decreased in control animals during the experimental procedure. On the other hand, animals given T3 had stable or (in one case) increasing adipose tissue cyclic AMP levels. Hence, T3, actually maintained higher levels than that expected, in comparison to the control. Cyclic GMP levels in adipose tissue were not affected by T3. Cyclic AMP and cyclic GMP were unchanged in muscle. In all cases, a time lag occurred (30-45 min) between administration of T3 and subsequent alterations in cyclic nucleotide levels. It was concluded that T3 is capable of altering concentrations of cyclic AMP and cyclic GMP in vivo and that cyclic AMP and cyclic GMP patterns of response are completely different. In liver, a converse relation of the two nucleotides is present. These findings are compatible with the hypothesis that some of T3's action may be explained by its effects upon either cyclic AMP or cyclic GMP.", "contents": "Alterations in cyclic necleotides in dogs after triiodothyronine. The effects of triiodothyronine (T3) on plasma and tissue levels (liver, adipose tissue, muscle) of adenosine 3',5'-monophosphate (cyclic GMP) were determined in Mongrel dogs. Plasma cyclic AMP increased to a mean plateau value 165% greater than control values in response to a single intravenous injection of T3 (100-200 mug/kg body weight). This treatment resulted in no increase in plasma cyclic GMP. In liver, cyclic AMP concentration decreased 54%, while cyclic GMP increased 137%. Adipose tissue cyclic AMP levels decreased in control animals during the experimental procedure. On the other hand, animals given T3 had stable or (in one case) increasing adipose tissue cyclic AMP levels. Hence, T3, actually maintained higher levels than that expected, in comparison to the control. Cyclic GMP levels in adipose tissue were not affected by T3. Cyclic AMP and cyclic GMP were unchanged in muscle. In all cases, a time lag occurred (30-45 min) between administration of T3 and subsequent alterations in cyclic nucleotide levels. It was concluded that T3 is capable of altering concentrations of cyclic AMP and cyclic GMP in vivo and that cyclic AMP and cyclic GMP patterns of response are completely different. In liver, a converse relation of the two nucleotides is present. These findings are compatible with the hypothesis that some of T3's action may be explained by its effects upon either cyclic AMP or cyclic GMP."} {"id": "PMID:165648", "title": "Glucose inhibiton of the permeation of chloromercuribenzene-p-sulphonic acid in the plasma membrane of pancreatic beta-cells.", "content": "The transport of chloromercuribenzene-p-sulphonic acid (CMBS) was studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Glucose inhibited the islet uptake of CMBS. The initial binding of CMBS to superficial thiol groups was inhibited to a lesser extent than was its further permeation into the interior of the plasma membrane. The non-metabolized glucose analogue 3-0-methyl glucose had no effect on the permeation of CMBS. Whereas mannoheptulose, epinephrine and diazoxide lacked any effect in themselves, they tended to counteract the glucose inhibition of CMBS permeation. The ability of glucose to inhibit CMBS permeation is related to its insulin-releasing action rather than to its membrane transport or further metabolism.", "contents": "Glucose inhibiton of the permeation of chloromercuribenzene-p-sulphonic acid in the plasma membrane of pancreatic beta-cells. The transport of chloromercuribenzene-p-sulphonic acid (CMBS) was studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Glucose inhibited the islet uptake of CMBS. The initial binding of CMBS to superficial thiol groups was inhibited to a lesser extent than was its further permeation into the interior of the plasma membrane. The non-metabolized glucose analogue 3-0-methyl glucose had no effect on the permeation of CMBS. Whereas mannoheptulose, epinephrine and diazoxide lacked any effect in themselves, they tended to counteract the glucose inhibition of CMBS permeation. The ability of glucose to inhibit CMBS permeation is related to its insulin-releasing action rather than to its membrane transport or further metabolism."} {"id": "PMID:165649", "title": "Age dependence of plasma oestrogen response to HCG and ACTH in men.", "content": "Twelve men, 19-40 years old, and 12 men, 60-86 years old, were given ACTH and in a second test series, HCG. Oestrone, oestradiol-17beta and cortisol were measured in the plasma before and after stimulation. Under basal conditions oestrone and oestradiol as well as the percentage binding of testosterone increased significantly with age, whereas cortisol remained unchanged. The administration of HCG resulted in higher levels of both plasma oestrone and oestradiol in older subjects than in younger ones, although the percentage increase was smaller. ACTH stimulation leads to higher levels of oestrone in the older group, whereas oestradiol remained unchanged. Cortisol rose 3.5 fold in both groups. Regarding absolute concentrations of oestrone and oestradiol the ability of the adrenals and of the testes to respond to exogenous gonadotrophin and adrenocorticotrophin appeared to be preserved despite ageing, though the relative responses of oestrone and oestradiol after HCG and of oestrone after ACTH were decreased in old as compared to young men.", "contents": "Age dependence of plasma oestrogen response to HCG and ACTH in men. Twelve men, 19-40 years old, and 12 men, 60-86 years old, were given ACTH and in a second test series, HCG. Oestrone, oestradiol-17beta and cortisol were measured in the plasma before and after stimulation. Under basal conditions oestrone and oestradiol as well as the percentage binding of testosterone increased significantly with age, whereas cortisol remained unchanged. The administration of HCG resulted in higher levels of both plasma oestrone and oestradiol in older subjects than in younger ones, although the percentage increase was smaller. ACTH stimulation leads to higher levels of oestrone in the older group, whereas oestradiol remained unchanged. Cortisol rose 3.5 fold in both groups. Regarding absolute concentrations of oestrone and oestradiol the ability of the adrenals and of the testes to respond to exogenous gonadotrophin and adrenocorticotrophin appeared to be preserved despite ageing, though the relative responses of oestrone and oestradiol after HCG and of oestrone after ACTH were decreased in old as compared to young men."} {"id": "PMID:165650", "title": "Effect of diethylnitrosamine on the livers of rats after high oral doses administered at intervals varying between three and twenty-four days.", "content": "When 200 mg of diethylnitrosamine per kg of body weight was administered with a stomach tube once a week to female Wistar W.64 rats, all of them died within three weeks from severe hepatocellular injuries and haemorrhages of the liver, lungs and small intestine. Weekly administrations of 100 mg per kg of body weight consistently caused the rats to die after seven to fifteen weeks from severe hepatic cirrhoses characterized by large tubercles. Weekly doses of 50 mg per kg of body weight caused much less severe hepatic cirrhosis. Under these conditions death occurred after 17 to 23 weeks, all the rats having contracted multiple hepatocellular carcinomas and in most cases pronounced hepatic cirrhosis. When this amount of diethylnitrosamine was administered for twelve weeks only the hepatic cirrhosis was less apparent, but a substantial influence on the tumor development was not observed. After a reduction of the dose to 25 mg per kg of body weight once a week all the rats in the relevant group died after 26 to 35 weeks, likewise from multiple hepatocellular carcinomas. Hepatic cirrhosis were then relatively inconspicuous. Similar results were obtained when, not the dose, but the interval between doses (100 mg/kg each) was varied. This clearly differential effect of diethylnitrosamine in the rat thus makes it a simple matter to induce hepatic cirrhosis or cancers that are suitable for a variety of tests and also, for example, as models for therapy trials.", "contents": "Effect of diethylnitrosamine on the livers of rats after high oral doses administered at intervals varying between three and twenty-four days. When 200 mg of diethylnitrosamine per kg of body weight was administered with a stomach tube once a week to female Wistar W.64 rats, all of them died within three weeks from severe hepatocellular injuries and haemorrhages of the liver, lungs and small intestine. Weekly administrations of 100 mg per kg of body weight consistently caused the rats to die after seven to fifteen weeks from severe hepatic cirrhoses characterized by large tubercles. Weekly doses of 50 mg per kg of body weight caused much less severe hepatic cirrhosis. Under these conditions death occurred after 17 to 23 weeks, all the rats having contracted multiple hepatocellular carcinomas and in most cases pronounced hepatic cirrhosis. When this amount of diethylnitrosamine was administered for twelve weeks only the hepatic cirrhosis was less apparent, but a substantial influence on the tumor development was not observed. After a reduction of the dose to 25 mg per kg of body weight once a week all the rats in the relevant group died after 26 to 35 weeks, likewise from multiple hepatocellular carcinomas. Hepatic cirrhosis were then relatively inconspicuous. Similar results were obtained when, not the dose, but the interval between doses (100 mg/kg each) was varied. This clearly differential effect of diethylnitrosamine in the rat thus makes it a simple matter to induce hepatic cirrhosis or cancers that are suitable for a variety of tests and also, for example, as models for therapy trials."} {"id": "PMID:165651", "title": "Studies of the plasma kinin-forming system in cirrhosis of the liver.", "content": "Kininogen level, that of active kinins and kininase activity in the plasma of patients suffering from cirrhosis of the liver and of healthy people were studied. The kininogen content was determined by different available methods i.e. the trypsin and acetone techniques and by means of the plasma and glandular kallikrein preparation. An increase in kininase activity and a lowered kininogen level as determined by all the methods were found in the sick persons. The maximal decrease in the kininogen level determined by means of the plasma kallikreins is substantiated in connection with the increased fibrinolytic activity of the plasma of the patients with hepatic cirrhosis.", "contents": "Studies of the plasma kinin-forming system in cirrhosis of the liver. Kininogen level, that of active kinins and kininase activity in the plasma of patients suffering from cirrhosis of the liver and of healthy people were studied. The kininogen content was determined by different available methods i.e. the trypsin and acetone techniques and by means of the plasma and glandular kallikrein preparation. An increase in kininase activity and a lowered kininogen level as determined by all the methods were found in the sick persons. The maximal decrease in the kininogen level determined by means of the plasma kallikreins is substantiated in connection with the increased fibrinolytic activity of the plasma of the patients with hepatic cirrhosis."} {"id": "PMID:165652", "title": "Virus antibody levels in serum specimens from patients with optic neuritis and from matched controls;.", "content": "Virus antibody levels in serum specimens taken in acute and convalescent phases from 77 patients with optic neuritits were tested by measles hamagglutination inhibition (HI), measles hemolysis inhibition (HLI), rubella HI, parainfluenza-1 HI, Epstein-Barr immunofluorescence (IF), and against 11 other viruses and mycoplasma pneumoniae with the complement fixation (CF) technique. The virus antibody levels were indicated to be usually very stable, and a fourfold change in virus antibody levels was demonstrated in only eight patients. The virus antibody levels were compared with specimens from two carefully selected control groups. The first control group consisted of 71 healthy persons matched in age, sex and place of residence with the patients with optic neuritis. The other control group consisted of 58 patients with various neurological diseases other than multiple sclerosis (MS) or infectious diseases of the central nervous system. The patients with optic neuritis had significantly higher measles antibody titres than the two control groups in both measles HI and measles HLI tests. Also in 33 patients with optic neuritis of unknown cause, the measles antibody levels were higher than in the control groups. On the other hand, various other antibody tests showed no statistically significant differences between patients with optic neuritis and the control group.", "contents": "Virus antibody levels in serum specimens from patients with optic neuritis and from matched controls;. Virus antibody levels in serum specimens taken in acute and convalescent phases from 77 patients with optic neuritits were tested by measles hamagglutination inhibition (HI), measles hemolysis inhibition (HLI), rubella HI, parainfluenza-1 HI, Epstein-Barr immunofluorescence (IF), and against 11 other viruses and mycoplasma pneumoniae with the complement fixation (CF) technique. The virus antibody levels were indicated to be usually very stable, and a fourfold change in virus antibody levels was demonstrated in only eight patients. The virus antibody levels were compared with specimens from two carefully selected control groups. The first control group consisted of 71 healthy persons matched in age, sex and place of residence with the patients with optic neuritis. The other control group consisted of 58 patients with various neurological diseases other than multiple sclerosis (MS) or infectious diseases of the central nervous system. The patients with optic neuritis had significantly higher measles antibody titres than the two control groups in both measles HI and measles HLI tests. Also in 33 patients with optic neuritis of unknown cause, the measles antibody levels were higher than in the control groups. On the other hand, various other antibody tests showed no statistically significant differences between patients with optic neuritis and the control group."} {"id": "PMID:165653", "title": "Virus antibody levels in the cerebrospinal fluid from patients with optic neuritis.", "content": "Virus antibody levels were studied in the cerebrospinal fluid (CSF) of 58 patients with optic neuritis and 58 control patients with no indication of multiple sclerosis (MS) or infectious disorders of the central nervous system (CNS). The specimens were tested against three different structural components of measles virus with measles hemagglutination inhibition (HI), measles hemolysis inhibition (HLI) and gel precipitation (GP) tests. Measles antibodies occurred in 62 per cent of CSF specimens from patients with optic neuritis, and 21 per cent of the controls. In the specimens from patients with optic neuritis, the positive rate figures were: for rubella HI test 35, parainfluenza-1 HI 16, and Epstein-Barr virus immunofuorescence (IF) 53 per cent. The frequencies in the control group were 10, 10 and 26 per cent, respectively. Serum/CSF antibody ratios below 80 occurred in measles tests in 45 per cent of patients with optic neuritis and 16 per cent of the control group. Some patients with optic neuritis (but none from the control group) had a reduced serum/CSF antibody ratio in more than one measles antibody test, The patients with optic neuritis had a higher frequency of low serum/CSF albumin ratios indicating blood brain barrier damage, There were, however, several patients with a normal serum/CSF albumin ratio but low serum/CSF immunoglobulin G and measles antibody ratios. This supports the hypothesis that local production of measles antibodies takes place in CNS in some patients with optic neuritis as well as in MS patients. The CSF specimens were further tested against 12 other viruses and mycoplasma pneumoniae complement fixation, but there were no positive specimens. New CSF specimens were taken from five patients during optic neuritis, and from seven patients later on during the follow-up because of the appearance of new neurological symptoms. There were no changes in virus antibody levels, except for two patients with an increase of measles virus antibody titres.", "contents": "Virus antibody levels in the cerebrospinal fluid from patients with optic neuritis. Virus antibody levels were studied in the cerebrospinal fluid (CSF) of 58 patients with optic neuritis and 58 control patients with no indication of multiple sclerosis (MS) or infectious disorders of the central nervous system (CNS). The specimens were tested against three different structural components of measles virus with measles hemagglutination inhibition (HI), measles hemolysis inhibition (HLI) and gel precipitation (GP) tests. Measles antibodies occurred in 62 per cent of CSF specimens from patients with optic neuritis, and 21 per cent of the controls. In the specimens from patients with optic neuritis, the positive rate figures were: for rubella HI test 35, parainfluenza-1 HI 16, and Epstein-Barr virus immunofuorescence (IF) 53 per cent. The frequencies in the control group were 10, 10 and 26 per cent, respectively. Serum/CSF antibody ratios below 80 occurred in measles tests in 45 per cent of patients with optic neuritis and 16 per cent of the control group. Some patients with optic neuritis (but none from the control group) had a reduced serum/CSF antibody ratio in more than one measles antibody test, The patients with optic neuritis had a higher frequency of low serum/CSF albumin ratios indicating blood brain barrier damage, There were, however, several patients with a normal serum/CSF albumin ratio but low serum/CSF immunoglobulin G and measles antibody ratios. This supports the hypothesis that local production of measles antibodies takes place in CNS in some patients with optic neuritis as well as in MS patients. The CSF specimens were further tested against 12 other viruses and mycoplasma pneumoniae complement fixation, but there were no positive specimens. New CSF specimens were taken from five patients during optic neuritis, and from seven patients later on during the follow-up because of the appearance of new neurological symptoms. There were no changes in virus antibody levels, except for two patients with an increase of measles virus antibody titres."} {"id": "PMID:165654", "title": "Congenital generalized lipodystrophy.", "content": "Six patients with congenital generalized lipodystrophy are described. They had generalized paucity of fat tissue, acanthosis nigricans, prominent superficial veins and muscle hypertrophy. They were mentally retarded. Three had corneal opacities. They had normal external genitalia and none was tall for age. Their bone age was advanced and some had minor skeletal anomalies and nephromegaly. The muscle histology on light microscopy was normal. The majority had elevated serum aldolase and to a lesser degree serum lactic dehydrogenase and creatinine phosphokinase. Four of five examined had a myopathic electromyogram. They had normal or deranged liver function tests. The fatty liver infiltration in one seems to be progressive. Four had a normal and two an abnormal metyrapone test. They had an age-dependent abnormality of growth hormone, insulin and carbohydrate homeostasis.", "contents": "Congenital generalized lipodystrophy. Six patients with congenital generalized lipodystrophy are described. They had generalized paucity of fat tissue, acanthosis nigricans, prominent superficial veins and muscle hypertrophy. They were mentally retarded. Three had corneal opacities. They had normal external genitalia and none was tall for age. Their bone age was advanced and some had minor skeletal anomalies and nephromegaly. The muscle histology on light microscopy was normal. The majority had elevated serum aldolase and to a lesser degree serum lactic dehydrogenase and creatinine phosphokinase. Four of five examined had a myopathic electromyogram. They had normal or deranged liver function tests. The fatty liver infiltration in one seems to be progressive. Four had a normal and two an abnormal metyrapone test. They had an age-dependent abnormality of growth hormone, insulin and carbohydrate homeostasis."} {"id": "PMID:165655", "title": "Preparation of type specific herpes simplex antisera by an immunosorbent method;.", "content": "Herpes simplex virus (HSV) type 1 and type 2 specific immune sera have been produced by adsorption with glutaraldehyde-polymerized heterologous virus antigen. The adsorbed sera showed high specificity in complement fixation, immunoelectroosmophoresis and neutralization tests, The precipitin patterns in IEOP indicate the presence of at least five HSV type 1 and three HSV type 2 specific antigens.", "contents": "Preparation of type specific herpes simplex antisera by an immunosorbent method;. Herpes simplex virus (HSV) type 1 and type 2 specific immune sera have been produced by adsorption with glutaraldehyde-polymerized heterologous virus antigen. The adsorbed sera showed high specificity in complement fixation, immunoelectroosmophoresis and neutralization tests, The precipitin patterns in IEOP indicate the presence of at least five HSV type 1 and three HSV type 2 specific antigens."} {"id": "PMID:165661", "title": "Beta-adrenergic receptors, cyclic AMP, and ion transport in the avian erythrocyte.", "content": "(1) Interaction of beta-adrenergic catecholamines with specific receptors on the cell membrane causes activation of adenylate cyclase, generation of intracellular cyclic 3',5'-AMP, and enhanced sodium and potassium transport. The effects of catecholamines on each of these functions are characteristic of beta1-type receptor interactions and are specific for 1(--)isomers. The order of effectiveness of agonists is isoproterenol greater than norepinephrine approximately equal to epinephrine. (2) exogenous cyclic 3',5'-AMP enhances sodium or potassium transport in a fashion identical to that caused by catecholamines. (3) the receptor contains an ethanolamine site that recognizes the stereospecific function of the agonist. Interaction at this site can be determined by measuring specific binding of a high specific activity-radioiodinated beta-blocker analogue (125-iodohydroxybenzylpindolol). Catecholamines bind at this site with affinities that parallel their biologic effectiveness as beta-adrenergic agonist. Beta-Blockers interact at this site with affinities that parallel their potencies as specific inhibitors of biologic function. (4) the adenylate cyclase complex contains a receptor site for guanyl nucleotides that is distinct from the catalytic site for ATP. Interaction at this site can be determined by measuring binding of radioactive guanylylimidodiphosphate (GMPPNP). GMPPNP markedly enhances the adenylate cyclase response to beta-adrenergic catecholamines with a 10-fold increase in apparent affinity of isoproterenol for activation of adenylate cyclase. Concomitantly there is a shift in Km and Vmax for ATP at the catalytic site. (5) Activation of adenylate cyclase by agonist or GMPPNP alone is reversible (GMPPNP remains bound even though the system returns to basal activity). The addition of isoproterenol plus GMPPNP, however, results in a state of enzyme activity which is apparently irreversible even though, under these conditions, the beta-adrenergic catecholamine freely dissociates from its receptor site. Under these conditions also the activated enzyme is not inhibited by the specific beta-blocker propranolol. (6) There is no evidence under adenylate cyclase assay conditions for a direct interaction of guanyl nucleotides with the beta-adrenergic receptor site nor for direct interaction of the agonist with the guanyl nucleotide site.", "contents": "Beta-adrenergic receptors, cyclic AMP, and ion transport in the avian erythrocyte. (1) Interaction of beta-adrenergic catecholamines with specific receptors on the cell membrane causes activation of adenylate cyclase, generation of intracellular cyclic 3',5'-AMP, and enhanced sodium and potassium transport. The effects of catecholamines on each of these functions are characteristic of beta1-type receptor interactions and are specific for 1(--)isomers. The order of effectiveness of agonists is isoproterenol greater than norepinephrine approximately equal to epinephrine. (2) exogenous cyclic 3',5'-AMP enhances sodium or potassium transport in a fashion identical to that caused by catecholamines. (3) the receptor contains an ethanolamine site that recognizes the stereospecific function of the agonist. Interaction at this site can be determined by measuring specific binding of a high specific activity-radioiodinated beta-blocker analogue (125-iodohydroxybenzylpindolol). Catecholamines bind at this site with affinities that parallel their biologic effectiveness as beta-adrenergic agonist. Beta-Blockers interact at this site with affinities that parallel their potencies as specific inhibitors of biologic function. (4) the adenylate cyclase complex contains a receptor site for guanyl nucleotides that is distinct from the catalytic site for ATP. Interaction at this site can be determined by measuring binding of radioactive guanylylimidodiphosphate (GMPPNP). GMPPNP markedly enhances the adenylate cyclase response to beta-adrenergic catecholamines with a 10-fold increase in apparent affinity of isoproterenol for activation of adenylate cyclase. Concomitantly there is a shift in Km and Vmax for ATP at the catalytic site. (5) Activation of adenylate cyclase by agonist or GMPPNP alone is reversible (GMPPNP remains bound even though the system returns to basal activity). The addition of isoproterenol plus GMPPNP, however, results in a state of enzyme activity which is apparently irreversible even though, under these conditions, the beta-adrenergic catecholamine freely dissociates from its receptor site. Under these conditions also the activated enzyme is not inhibited by the specific beta-blocker propranolol. (6) There is no evidence under adenylate cyclase assay conditions for a direct interaction of guanyl nucleotides with the beta-adrenergic receptor site nor for direct interaction of the agonist with the guanyl nucleotide site."} {"id": "PMID:165657", "title": "Behavioral effects of dibutyryl cyclic 3'5'AMP and biogenic amines in rats.", "content": "White male Wistar rats were injected intraventricularly with 200 mug of dibutyryl cyclic 3'5'AMP (DAMP. 30 min later part of animals was injected intraventricularly with 10 mug of dopamine (DA), 10 mug of 5-hydroxytryptamine (5-HT) or 50 mug of acetylcholine (Ach). Immediately after injection of the amines the time of walking, convulsions, immobility and number of jumps during 10 min periods of observation was measured. DAMP induced excitation of animals expressed by convulsions, jumping and short period of immobility. All studied biogenic amines inhibited convulsions and caused periodically stereotypical behavior. 5-HT and Ach increased the time of immobility in animals injected with DAMP. DA increased the number of jumping. These results indicate the interaction between DAMP and DA, 5-HT and Ach on behavioral phenomena in rats.", "contents": "Behavioral effects of dibutyryl cyclic 3'5'AMP and biogenic amines in rats. White male Wistar rats were injected intraventricularly with 200 mug of dibutyryl cyclic 3'5'AMP (DAMP. 30 min later part of animals was injected intraventricularly with 10 mug of dopamine (DA), 10 mug of 5-hydroxytryptamine (5-HT) or 50 mug of acetylcholine (Ach). Immediately after injection of the amines the time of walking, convulsions, immobility and number of jumps during 10 min periods of observation was measured. DAMP induced excitation of animals expressed by convulsions, jumping and short period of immobility. All studied biogenic amines inhibited convulsions and caused periodically stereotypical behavior. 5-HT and Ach increased the time of immobility in animals injected with DAMP. DA increased the number of jumping. These results indicate the interaction between DAMP and DA, 5-HT and Ach on behavioral phenomena in rats."} {"id": "PMID:165662", "title": "Thyrotropin-receptor interaction and cyclic AMP-mediated effects in thyroid cells.", "content": "Thyroid cells in culture constitute a suitable system for the study of thyroid gland function and its regulation. The natural thyroid stimulator (TSH) induces the in vitro reorganization of thyroid cells into three-dimensional follicles morphologically and metabolically similar to gland follicles. In contrast, nonstimulated cells develop as a monolayer and in a concerted manner rapidly lose the enzymes involved in iodine metabolosm and the aptitude to bind TSH to specific receptor sites. The morphogenetic action of TSH and its ability to maintain the specific metabolic properties of thyroid cells in culture are mediated by cyclic AMP via new RNA and new protein synthesis. Therefore comparison of the properties of a given cell type in morphologically and metabolically different status should provide a valuable tool for studying the TSH mechanism of action. Using 125-I-labeled TSH of high purity, high specific radioactivity, and preserved biologic potency, TSH interaction with intact cells and their derived plasma membranes was studied. At both the cellular and the sub-cellular level a very good agreement was found for the values of the rate and equilibrium constants of labeled TSH binding. A single type of high-affinity low-capacity site was revealed. In contrast, in both systems dissociation of bound labeled TSH was not of single-order kinetics and showed two kinetic components with half-lives of 3 and 30 min. An excellent correlation between half-stimulation of adenylate cyclase and iodide transport mechanism activation, and the dissociation constant of TSH binding, was found, indicating that the in vitro system studied was relevant to physiologic regulation.", "contents": "Thyrotropin-receptor interaction and cyclic AMP-mediated effects in thyroid cells. Thyroid cells in culture constitute a suitable system for the study of thyroid gland function and its regulation. The natural thyroid stimulator (TSH) induces the in vitro reorganization of thyroid cells into three-dimensional follicles morphologically and metabolically similar to gland follicles. In contrast, nonstimulated cells develop as a monolayer and in a concerted manner rapidly lose the enzymes involved in iodine metabolosm and the aptitude to bind TSH to specific receptor sites. The morphogenetic action of TSH and its ability to maintain the specific metabolic properties of thyroid cells in culture are mediated by cyclic AMP via new RNA and new protein synthesis. Therefore comparison of the properties of a given cell type in morphologically and metabolically different status should provide a valuable tool for studying the TSH mechanism of action. Using 125-I-labeled TSH of high purity, high specific radioactivity, and preserved biologic potency, TSH interaction with intact cells and their derived plasma membranes was studied. At both the cellular and the sub-cellular level a very good agreement was found for the values of the rate and equilibrium constants of labeled TSH binding. A single type of high-affinity low-capacity site was revealed. In contrast, in both systems dissociation of bound labeled TSH was not of single-order kinetics and showed two kinetic components with half-lives of 3 and 30 min. An excellent correlation between half-stimulation of adenylate cyclase and iodide transport mechanism activation, and the dissociation constant of TSH binding, was found, indicating that the in vitro system studied was relevant to physiologic regulation."} {"id": "PMID:165664", "title": "Ca-2+/Mg-2+-dependent cyclic nucleotide phosphodiesterase and its activator protein.", "content": "(1) Ca-2+/Mg-2+-dependent cyclic nucleotide phosphodiesterase was found in the supernatant fluids of a variety of tissues, including cerebral cortex, cerebellum, kidney, liver, and heart. (2) this enzyme required Ca-2+, Mg-2+, and an activator protein (PAF) for the activity. In the presence of these ingredients the enzyme hydrolyzed cyclic GMP preferentially when incubated with a low concentration (0.4 muM) of substrate. (3) The enzyme devoid of PAF was eluted in fraction II with a molecular weight of approximately 150,000 after Sephadex G-200 gel filtration of the supernatant fluids using medium containing EGTA. PAF thus separated from the enzyme was eluted in a fraction corresponding to a molecular weight of approximately 28,000 by gel filtration. Stimulation of the activity of fraction II by Ca-2+ was completely dependent on the addition of PAF. (4) Formation of an active enzyme-PAF complex with an estimated molecular weight of 200,000 was demonstrated by gel filtration of a mixture of the enzyme and PAF in medium containing Ca-2+. It is likely that the activity of the Ca-2+/Mg-2+ in a concentration range of approximately 1 to 10 muM, as shown in the following equation: [Enzyme] inactive + PAF + Ca-2+ in equilibrium [enzyme - PAF - Ca-2+] active. More than one PAF protein may bind to one molecule of enzyme to form an active complex. Equilibrium of the above equation is probably determined mainly by the intracellular concentration of Ca-2+ in vivo. (5) The enzyme-PAF complex was more labile after heat treatment than the free form of enzyme. (6) PAF was isolated from all tissues listed in (1). The levels of PAF and of fraction II did not correspond exactly.", "contents": "Ca-2+/Mg-2+-dependent cyclic nucleotide phosphodiesterase and its activator protein. (1) Ca-2+/Mg-2+-dependent cyclic nucleotide phosphodiesterase was found in the supernatant fluids of a variety of tissues, including cerebral cortex, cerebellum, kidney, liver, and heart. (2) this enzyme required Ca-2+, Mg-2+, and an activator protein (PAF) for the activity. In the presence of these ingredients the enzyme hydrolyzed cyclic GMP preferentially when incubated with a low concentration (0.4 muM) of substrate. (3) The enzyme devoid of PAF was eluted in fraction II with a molecular weight of approximately 150,000 after Sephadex G-200 gel filtration of the supernatant fluids using medium containing EGTA. PAF thus separated from the enzyme was eluted in a fraction corresponding to a molecular weight of approximately 28,000 by gel filtration. Stimulation of the activity of fraction II by Ca-2+ was completely dependent on the addition of PAF. (4) Formation of an active enzyme-PAF complex with an estimated molecular weight of 200,000 was demonstrated by gel filtration of a mixture of the enzyme and PAF in medium containing Ca-2+. It is likely that the activity of the Ca-2+/Mg-2+ in a concentration range of approximately 1 to 10 muM, as shown in the following equation: [Enzyme] inactive + PAF + Ca-2+ in equilibrium [enzyme - PAF - Ca-2+] active. More than one PAF protein may bind to one molecule of enzyme to form an active complex. Equilibrium of the above equation is probably determined mainly by the intracellular concentration of Ca-2+ in vivo. (5) The enzyme-PAF complex was more labile after heat treatment than the free form of enzyme. (6) PAF was isolated from all tissues listed in (1). The levels of PAF and of fraction II did not correspond exactly."} {"id": "PMID:165666", "title": "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase.", "content": "The brain as well as other mammalian tissues contains several different forms of cyclic nucleotide phosphodiesterase separable by polyacrylamide gel electrophoresis. Each tissue and each individual type of cell has its own distinctive pattern and ratio of these multiple forms of phosphodiesterase. The different forms have several distinguishing properties and characteristics, and their activities may be differentially regulated both acutely and chronically. The enzyme forms have different stabilities, kinetic properties, substrate specificities, and sensitivities to an endogenous activator and to several inhibitors of phosphodiesterase. The phosphodiesterase inhibitors studied not only inhibit the different forms of phosphodiesterase to different degrees but apparently do so by different mechanisms. Thus whereas theophylline, cyclic GMP, and low concentrations of papaverine inhibit the phosphodiesterases by competing with the substrate (cyclic AMP), trifluoperazine apparently inhibits phosphodiesterase by interfering with the phosphodiesterase activator. This confers a great deal of specificity to this drug, since only one form of phosphodiesterase is markedly activated by the activator. Chronically, a specific form of phosphodiesterase appears to be inducible. This induction is probably controlled by the intracellular cyclic AMP concentration. The phosphodiesterase activator also appears to be regulatable, the age of the animal being one of the factors controlling its activity. Finally, since different types of cells have different relative amounts of the phosphodiesterases and since these forms of the enzyme can be differentially inhibited by drugs, it may be possible to develop drugs which will selectively increase the cyclic AMP concentration in discrete cell types. Evidence that cyclic AMP is involved in certain disease states suggests further that by selectively altering the concentration of cyclic AMP in these cells, one might be able to alter the course of the disease.", "contents": "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase. The brain as well as other mammalian tissues contains several different forms of cyclic nucleotide phosphodiesterase separable by polyacrylamide gel electrophoresis. Each tissue and each individual type of cell has its own distinctive pattern and ratio of these multiple forms of phosphodiesterase. The different forms have several distinguishing properties and characteristics, and their activities may be differentially regulated both acutely and chronically. The enzyme forms have different stabilities, kinetic properties, substrate specificities, and sensitivities to an endogenous activator and to several inhibitors of phosphodiesterase. The phosphodiesterase inhibitors studied not only inhibit the different forms of phosphodiesterase to different degrees but apparently do so by different mechanisms. Thus whereas theophylline, cyclic GMP, and low concentrations of papaverine inhibit the phosphodiesterases by competing with the substrate (cyclic AMP), trifluoperazine apparently inhibits phosphodiesterase by interfering with the phosphodiesterase activator. This confers a great deal of specificity to this drug, since only one form of phosphodiesterase is markedly activated by the activator. Chronically, a specific form of phosphodiesterase appears to be inducible. This induction is probably controlled by the intracellular cyclic AMP concentration. The phosphodiesterase activator also appears to be regulatable, the age of the animal being one of the factors controlling its activity. Finally, since different types of cells have different relative amounts of the phosphodiesterases and since these forms of the enzyme can be differentially inhibited by drugs, it may be possible to develop drugs which will selectively increase the cyclic AMP concentration in discrete cell types. Evidence that cyclic AMP is involved in certain disease states suggests further that by selectively altering the concentration of cyclic AMP in these cells, one might be able to alter the course of the disease."} {"id": "PMID:165668", "title": "Mechanisms of control for cAMP-dependent protein kinase from skeletal muscle.", "content": "A number of properties of homogeneous cyclic 3',5'-AMP (cAMP)-dependent protein kinase from rabbit skeletal muscle were determined. The enzyme is shown to be a tetramer consisting of one regulatory subunit dimer and two catalytic subunit monomers. Skeletal muscle protein kinase interacts with cAMP and MgATP as illustrated in the following equilibrium expression: R2C2 - (MgATP)2 + 2 cAMP in equilibrium R2 - (cAMP)2 + 2C + 2 MgATP. MgATP is shown to decrease the affinity of the enzyme for cAMP and to be necessary for recombination of the subunits. The concentration of the enzyme in tissue relative to that of cAMP is high enough to influence kinetic parameters of the activation process by cAMP. The cumulative effects of MgATP and high enzyme concentration are to increase the apparent activation constant for cAMP so that in vivo the enzyme would not be highly activated under basal conditions but would be greatly stimulated by increases in cAMP concentration. As a result, it is not necessary to invoke the concept of compartmentalization of cAMP to explain how it could regulate protein kinase activity in vivo. Finally, data are presented which indicate that a possible function of the heat-stable protein inhibitor of cAMP-dependent protein kinases may be to suppress the activity of protein kinase due to basal concentrations of cAMP. As such, the inhibitor could indirectly change the amount of cAMP needed to allow expression of protein kinase activity.", "contents": "Mechanisms of control for cAMP-dependent protein kinase from skeletal muscle. A number of properties of homogeneous cyclic 3',5'-AMP (cAMP)-dependent protein kinase from rabbit skeletal muscle were determined. The enzyme is shown to be a tetramer consisting of one regulatory subunit dimer and two catalytic subunit monomers. Skeletal muscle protein kinase interacts with cAMP and MgATP as illustrated in the following equilibrium expression: R2C2 - (MgATP)2 + 2 cAMP in equilibrium R2 - (cAMP)2 + 2C + 2 MgATP. MgATP is shown to decrease the affinity of the enzyme for cAMP and to be necessary for recombination of the subunits. The concentration of the enzyme in tissue relative to that of cAMP is high enough to influence kinetic parameters of the activation process by cAMP. The cumulative effects of MgATP and high enzyme concentration are to increase the apparent activation constant for cAMP so that in vivo the enzyme would not be highly activated under basal conditions but would be greatly stimulated by increases in cAMP concentration. As a result, it is not necessary to invoke the concept of compartmentalization of cAMP to explain how it could regulate protein kinase activity in vivo. Finally, data are presented which indicate that a possible function of the heat-stable protein inhibitor of cAMP-dependent protein kinases may be to suppress the activity of protein kinase due to basal concentrations of cAMP. As such, the inhibitor could indirectly change the amount of cAMP needed to allow expression of protein kinase activity."} {"id": "PMID:165670", "title": "Hormonal regulation of adenosine 3',5'-monophosphate-dependent protein kinase.", "content": "There appear to be two classes of protein kinases in rat heart and adipose tissue, types I and II. Type I elutes from DEAE-cellulose at smaller than 0.1 M NaCl and type II at greater than 0.1 M NaCl. The type I enzyme is more readily dissociated by salt or histone than is the type II enzyme. If the type I kinase is first dissociated by cAMP, the subunits reassociate very slowly at 0 degrees C on removal of the cAMP by Sephadex G-25 chromatography, whereas those of type II reassociate very rapidly. Rat heart contains mostly type I and a small amount of type II enzyme, whereas adipose tissue contains almost exclusively the type II enzyme. The adipose tissue enzyme resembles the heart type II kinase in all of the above properties, although the two enzymes are not identical as indicated by slight differences in elution patterns from DEAE-cellulose columns. Incubation of rat epididymal adipose tissue with low concentrations of epinephrine (0.11 muM) increases glycerol production and the fraction of the protein kinase in the active form (activity ratio). The change in cAMP under these conditions is not statistically significant. The presence of insulin inhibits the epinephrine effect on glycerol production and protein kinase but has no measurable effect on cAMP levels. Incubation of adipose tissue with high epinephrine concentrations (11 muM) increases the cAMP level, the protein kinase activity ratio, and glycerol production. Under these conditions insulin decreases the cAMP level and kinase activity ratio but does not reduce glycerol production. The data suggest that very small changes in the tissue cAMP level, undetectable by the assay method, are magnified during the stepwise activation of glycerol output aided possibly by cooperative effects between cAMP and protein kinase. The procedure developed for determining the state of activation of the cAMP-dependent protein kinase in adipose tissue must be modified by reducing the salt concentration of the buffers in order to carry out similar studies in the heart. This reflects the different types of protein kinase in the two tissues. The addition of charcoal to crude extracts of heart prevents protein kinase activation by added cyclic AMP. Charcoal should therefore prevent any activation that could occur if any sequestered cAMP were released during homogenization. Charcoal addition thereby provides a means to distinguish intracellular cAMP activation of the kinase from that which might occur following cell rupture. If epinephrine-perfused hearts are homogenized in the presence of charcoal, epinephrine stimulation of the protein kinase is only slightly decreased. This indicates that the protein kinase is activated intracellularly by cAMP and suggests that all of the cAMP in the cell is available to the protein kinase; i.e., cAMP is not released during homogenization.", "contents": "Hormonal regulation of adenosine 3',5'-monophosphate-dependent protein kinase. There appear to be two classes of protein kinases in rat heart and adipose tissue, types I and II. Type I elutes from DEAE-cellulose at smaller than 0.1 M NaCl and type II at greater than 0.1 M NaCl. The type I enzyme is more readily dissociated by salt or histone than is the type II enzyme. If the type I kinase is first dissociated by cAMP, the subunits reassociate very slowly at 0 degrees C on removal of the cAMP by Sephadex G-25 chromatography, whereas those of type II reassociate very rapidly. Rat heart contains mostly type I and a small amount of type II enzyme, whereas adipose tissue contains almost exclusively the type II enzyme. The adipose tissue enzyme resembles the heart type II kinase in all of the above properties, although the two enzymes are not identical as indicated by slight differences in elution patterns from DEAE-cellulose columns. Incubation of rat epididymal adipose tissue with low concentrations of epinephrine (0.11 muM) increases glycerol production and the fraction of the protein kinase in the active form (activity ratio). The change in cAMP under these conditions is not statistically significant. The presence of insulin inhibits the epinephrine effect on glycerol production and protein kinase but has no measurable effect on cAMP levels. Incubation of adipose tissue with high epinephrine concentrations (11 muM) increases the cAMP level, the protein kinase activity ratio, and glycerol production. Under these conditions insulin decreases the cAMP level and kinase activity ratio but does not reduce glycerol production. The data suggest that very small changes in the tissue cAMP level, undetectable by the assay method, are magnified during the stepwise activation of glycerol output aided possibly by cooperative effects between cAMP and protein kinase. The procedure developed for determining the state of activation of the cAMP-dependent protein kinase in adipose tissue must be modified by reducing the salt concentration of the buffers in order to carry out similar studies in the heart. This reflects the different types of protein kinase in the two tissues. The addition of charcoal to crude extracts of heart prevents protein kinase activation by added cyclic AMP. Charcoal should therefore prevent any activation that could occur if any sequestered cAMP were released during homogenization. Charcoal addition thereby provides a means to distinguish intracellular cAMP activation of the kinase from that which might occur following cell rupture. If epinephrine-perfused hearts are homogenized in the presence of charcoal, epinephrine stimulation of the protein kinase is only slightly decreased. This indicates that the protein kinase is activated intracellularly by cAMP and suggests that all of the cAMP in the cell is available to the protein kinase; i.e., cAMP is not released during homogenization."} {"id": "PMID:165675", "title": "Regulation of cyclic GMP levels in the ductus deferens of the rat.", "content": "The cyclic GMP level in the ductus deferens is elevated by acetylcholine, norepinephrine, KCl, and the phosphodiesterase inhibitor SC-2964. The presence of extracellular Ca++ is required for the effects of all of these agents on cyclic GMP levels. In addition, Ca++ appears to be an important factor for the basal turnover of cyclic GMP in this tissue, but it may be less important in other tissues. These observations have led us to the following working hypothesis (Fig. 5): The interactions of some hormones or neurotransmitters with membrane receptors secondarily increase cyclic GMP formation after primarily increasing the influx of extracellular Ca++ or changing the distribution of Ca++ among intracellular pools or compartments. However, in addition to this possibility, other hormonal effects on particulate and/or soluble guanylate cyclase that do not involve Ca++ mediation must also be considered. Some agents that are known to increase cyclic GMP in tissues have been reported in preliminary communications to activate cell-free preparations of guanylate cyclase (Amer and McKINNEY, 1973; White, Ignarro, and George, 1973), but these reports have not yet been confirmed by other laboratories. Secretin has been reported to stimulate guanylate cyclase activity from several tissues (Thompson, Johnson, Lavis, and Williams, 1974), but the significance of this report is unclear since secretin has not yet been shown to increase cyclic GMP levels in any tissue. Thus, although not convincingly established, some hormones may increase particulate guanylate cyclase activity in a manner similar to that by which hormones increase adenylate cyclase activity. Alternatively, some hormones may increase soluble guanylate cyclase activity with mediating factors other than Ca++ being involved, or hormone-receptor interaction at the plasma membrane could conceivably induce a dislocation and change in effective activity of a reversibly bound, membrane-associated guanylate cyclase. Elucidating which or how many of these possibilities are operative will require thorough study and understanding of the fundamental behavior and properties of soluble and particulate guanylate cyclase activities.", "contents": "Regulation of cyclic GMP levels in the ductus deferens of the rat. The cyclic GMP level in the ductus deferens is elevated by acetylcholine, norepinephrine, KCl, and the phosphodiesterase inhibitor SC-2964. The presence of extracellular Ca++ is required for the effects of all of these agents on cyclic GMP levels. In addition, Ca++ appears to be an important factor for the basal turnover of cyclic GMP in this tissue, but it may be less important in other tissues. These observations have led us to the following working hypothesis (Fig. 5): The interactions of some hormones or neurotransmitters with membrane receptors secondarily increase cyclic GMP formation after primarily increasing the influx of extracellular Ca++ or changing the distribution of Ca++ among intracellular pools or compartments. However, in addition to this possibility, other hormonal effects on particulate and/or soluble guanylate cyclase that do not involve Ca++ mediation must also be considered. Some agents that are known to increase cyclic GMP in tissues have been reported in preliminary communications to activate cell-free preparations of guanylate cyclase (Amer and McKINNEY, 1973; White, Ignarro, and George, 1973), but these reports have not yet been confirmed by other laboratories. Secretin has been reported to stimulate guanylate cyclase activity from several tissues (Thompson, Johnson, Lavis, and Williams, 1974), but the significance of this report is unclear since secretin has not yet been shown to increase cyclic GMP levels in any tissue. Thus, although not convincingly established, some hormones may increase particulate guanylate cyclase activity in a manner similar to that by which hormones increase adenylate cyclase activity. Alternatively, some hormones may increase soluble guanylate cyclase activity with mediating factors other than Ca++ being involved, or hormone-receptor interaction at the plasma membrane could conceivably induce a dislocation and change in effective activity of a reversibly bound, membrane-associated guanylate cyclase. Elucidating which or how many of these possibilities are operative will require thorough study and understanding of the fundamental behavior and properties of soluble and particulate guanylate cyclase activities."} {"id": "PMID:165678", "title": "Relationship between cyclic AMP metabolism and inotropic response of perfused rat hearts to phenylephrine and other adrenergic amines.", "content": "A positive correlation between inotropic response and increment of cyclic AMP levels and labeling (from 14-C-adenine in the perfusate) was found after isoprenaline, dopamine, and phenylephrine alone, and after isoprenaline in the presence of chlorpromazine. 2. a lack of correlation between contractile activity and cyclic AMP levels and labeling was found when the hearts were exposed to phenylephrine in the presence of propranolol. The contractile activity increased, but the parameters for cyclic AMP did not change. These resuls together with findings by other workers indicate that the inotropic response to beta-stimulation always is associated with cyclic AMP accumulation, while the inotropic response to alpha-stimulation (when present) is not correlated to cyclic AMP elevation. Other differences between alpha- and beta-adrenergic effects on heart (course of development of the inotropic response, effect of theophylline on the response, effects on relaxing processes, action potential, and on refractory period) also indicate different mechanisms of action. On the basis of the available data we suggest as a conclusion that the inotropic response after alpha-adrenergic stimulation does not involve cyclic AMP as a mediator whereas beta-adrenergic effects are mediated by cyclic AMP. This means that the naturally occurring adrenergic amines norepinephrine and epinephrine, both of which are able to stimulate both alpha and beta myocardial receptors (twenzel and Su, 1966), elicit the inotropic response through two different mechanisms. Usually the beta-adrenergic effect on the heart is the more important. The contribution from alpha-stimulation, however, may increase under certain conditions: hypothyroidism or proplythiouracil treatment per se (Nakashima et al., 1971) or hypothermia (Kunos and Szentiv\u00e1nyi, 1968; Buckley and Jordan. 1970; Benfey et al., 1973; Kunos, Yong, and Nickerson, 1973; Nickerson, 1973). Thus a single physiologic response may be mediated by more than one mechanism. Multiple mechanisms of action for one agent might have more general biologic significance; e.g., they may serve to maintain the responsiveness of a tissue under various conditions.", "contents": "Relationship between cyclic AMP metabolism and inotropic response of perfused rat hearts to phenylephrine and other adrenergic amines. A positive correlation between inotropic response and increment of cyclic AMP levels and labeling (from 14-C-adenine in the perfusate) was found after isoprenaline, dopamine, and phenylephrine alone, and after isoprenaline in the presence of chlorpromazine. 2. a lack of correlation between contractile activity and cyclic AMP levels and labeling was found when the hearts were exposed to phenylephrine in the presence of propranolol. The contractile activity increased, but the parameters for cyclic AMP did not change. These resuls together with findings by other workers indicate that the inotropic response to beta-stimulation always is associated with cyclic AMP accumulation, while the inotropic response to alpha-stimulation (when present) is not correlated to cyclic AMP elevation. Other differences between alpha- and beta-adrenergic effects on heart (course of development of the inotropic response, effect of theophylline on the response, effects on relaxing processes, action potential, and on refractory period) also indicate different mechanisms of action. On the basis of the available data we suggest as a conclusion that the inotropic response after alpha-adrenergic stimulation does not involve cyclic AMP as a mediator whereas beta-adrenergic effects are mediated by cyclic AMP. This means that the naturally occurring adrenergic amines norepinephrine and epinephrine, both of which are able to stimulate both alpha and beta myocardial receptors (twenzel and Su, 1966), elicit the inotropic response through two different mechanisms. Usually the beta-adrenergic effect on the heart is the more important. The contribution from alpha-stimulation, however, may increase under certain conditions: hypothyroidism or proplythiouracil treatment per se (Nakashima et al., 1971) or hypothermia (Kunos and Szentiv\u00e1nyi, 1968; Buckley and Jordan. 1970; Benfey et al., 1973; Kunos, Yong, and Nickerson, 1973; Nickerson, 1973). Thus a single physiologic response may be mediated by more than one mechanism. Multiple mechanisms of action for one agent might have more general biologic significance; e.g., they may serve to maintain the responsiveness of a tissue under various conditions."} {"id": "PMID:165680", "title": "Control of calcium transport in the myocardium by the cyclic AMP-Protein kinase system.", "content": "At least three mechanical changes characterize the response of cardiac muscle to agents that enhance cyclic AMP production. In common with other inotropic interventions, tension is augmented and the rate of tension rise is increased. The third response, acceleration of the rate of relaxation, is characteristic of the actions of beta-adrenergic agonists. These mechanical effects can be attributed to changes in (1) the amount of Ca2+ released during systole, (2) the rate of Ca2+ release at the onset of systole, and (3) the rate at which Ca2+ is reaccumulated by the sarcoplasmic reticulum at the end of systole. The ability of cyclic AMP-dependent protein kinases to phosphorylate the cardiac sarcoplasmic reticulum in vitro parallels stimulation of both Ca2+ transport and Ca2+-activated ATPase. The phosphoprotein formed in the presence of cyclic AMP and protein kinase has the chemical characteristics of a phosphoester, contains mostly phosphoserine, and has an electrophoretic mobility in SDS polyacrylamide gels that corresponds to a protein of 22,000 daltons. This 22,000-dalton protein, tentatively named phospholamban, thus differs from the acyl phosphooprotein formed by the Ca2+-transport ATPase, which as an apparent molecular weight of 90,000 to 100,000 daltons. Phospholamban has not been found in fast skeletal muscle, nor is Ca2+ transport accelerated by cyclic AMP and protein kinase in sarcoplasmic reticulum from these muslces which do not respond to beta-adrenergic agonists with accelerated relaxation. It thus appears likely that phosphorylation of phospholamban correlates both with an increased rate of Ca2+ transport by cardiac sarcoplasmic reticulum in vitro and accelerated relaxation in the intact myocardium. Preliminary findings are consistent with the view that phosphorylation of phospholamban may be related to other actions on Ca2+ fluxes brought about by agents which activate adenylate cyclase in the myocardium, but these interpretations must remain speculative pending more definitive studies.", "contents": "Control of calcium transport in the myocardium by the cyclic AMP-Protein kinase system. At least three mechanical changes characterize the response of cardiac muscle to agents that enhance cyclic AMP production. In common with other inotropic interventions, tension is augmented and the rate of tension rise is increased. The third response, acceleration of the rate of relaxation, is characteristic of the actions of beta-adrenergic agonists. These mechanical effects can be attributed to changes in (1) the amount of Ca2+ released during systole, (2) the rate of Ca2+ release at the onset of systole, and (3) the rate at which Ca2+ is reaccumulated by the sarcoplasmic reticulum at the end of systole. The ability of cyclic AMP-dependent protein kinases to phosphorylate the cardiac sarcoplasmic reticulum in vitro parallels stimulation of both Ca2+ transport and Ca2+-activated ATPase. The phosphoprotein formed in the presence of cyclic AMP and protein kinase has the chemical characteristics of a phosphoester, contains mostly phosphoserine, and has an electrophoretic mobility in SDS polyacrylamide gels that corresponds to a protein of 22,000 daltons. This 22,000-dalton protein, tentatively named phospholamban, thus differs from the acyl phosphooprotein formed by the Ca2+-transport ATPase, which as an apparent molecular weight of 90,000 to 100,000 daltons. Phospholamban has not been found in fast skeletal muscle, nor is Ca2+ transport accelerated by cyclic AMP and protein kinase in sarcoplasmic reticulum from these muslces which do not respond to beta-adrenergic agonists with accelerated relaxation. It thus appears likely that phosphorylation of phospholamban correlates both with an increased rate of Ca2+ transport by cardiac sarcoplasmic reticulum in vitro and accelerated relaxation in the intact myocardium. Preliminary findings are consistent with the view that phosphorylation of phospholamban may be related to other actions on Ca2+ fluxes brought about by agents which activate adenylate cyclase in the myocardium, but these interpretations must remain speculative pending more definitive studies."} {"id": "PMID:165683", "title": "Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism.", "content": "Studies using perfused rat liver and isolated liver parenchymal cells show that low concentrations of epinephrine, norepinephrine, and phenylephrine can activate glycogenolysis and gluconeogenesis by a mechanism mediated by alpha-adrenergic receptors and not involving accumulation of cAMP. The glycogenolytic and gluconeogenic activites of epinephrine, norepinephrine, and phenylephrine are inhibited by the alpha-adrenergic receptor antagonists phentolamine and dihydroergotamine, but are negligibly affected by the beta-adrenergic receptor antagonist propranolol. Epinephrine, norephinephrine, and the beta-adrenergic receptor agonists isoproterenol, soterenol, and salbutamol increase cAMP accumulation; and this effect is antagonized by propranolol. Isoproterenol, soterenol, and salbutamol activate glycogenolysis and gluconeogenesis, but are less effective than epinephrine or norepinephrine. The data are interpreted as indicating the existence of both alpha- and beta-adrenergic receptors in rat liver. Activation of the alpha-adrenergic mechanism appears to be more important than the beta-adrenergic receptor-cAMP system in the physiologic effects of epinephrine and norepinephrine on carbohydrate metabolism in rat liver.", "contents": "Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism. Studies using perfused rat liver and isolated liver parenchymal cells show that low concentrations of epinephrine, norepinephrine, and phenylephrine can activate glycogenolysis and gluconeogenesis by a mechanism mediated by alpha-adrenergic receptors and not involving accumulation of cAMP. The glycogenolytic and gluconeogenic activites of epinephrine, norepinephrine, and phenylephrine are inhibited by the alpha-adrenergic receptor antagonists phentolamine and dihydroergotamine, but are negligibly affected by the beta-adrenergic receptor antagonist propranolol. Epinephrine, norephinephrine, and the beta-adrenergic receptor agonists isoproterenol, soterenol, and salbutamol increase cAMP accumulation; and this effect is antagonized by propranolol. Isoproterenol, soterenol, and salbutamol activate glycogenolysis and gluconeogenesis, but are less effective than epinephrine or norepinephrine. The data are interpreted as indicating the existence of both alpha- and beta-adrenergic receptors in rat liver. Activation of the alpha-adrenergic mechanism appears to be more important than the beta-adrenergic receptor-cAMP system in the physiologic effects of epinephrine and norepinephrine on carbohydrate metabolism in rat liver."} {"id": "PMID:165684", "title": "Glucagon and adenylate cyclase: binding studies and requirements for activation.", "content": "Solubilization of myocardial adenylate cyclase abolished responsiveness to glucagon and catecholamines, two of the hormones which activate the membrane-bound enzyme. Adenylate cyclase freed of detergent by DEAE-cellulose chromatography continues to remain unresponsive to hormone stimulation. However, adding purified bovine brain phospholipids--phosphotidylserine and monophosphatidylinositol--restored responsiveness to glucagon and catecholamines, respectively. 125-i-glucagon binding appeared to be independent of phospholipid, since equal binding was observed in the presence or absence of detergent and in the presence or absence of phospholipids. Chromatography of the solubilized preparation on Sephadex G-100 WAS CHARACTERIZED BY 125-I-glucagon binding and fluoride-stimulatable adenylate cyclase activity appearing in the fractions consistent with the void volume, suggesting a molecular weight greater than 100,000 for the receptor-adenylate cyclase complex. Prior incubation of the binding peak with 125-I-glucagon and rechromatography of the bound glucagon on Sephadex G-100 shifted its elution to a later fraction consistent with a smaller-molecular-weight peak. The molecular weight of this material was 24,000 to 28,000, as determined by SDS polyacrylamide gel electrophoresis. The latter findings are consistent with a dissociable receptor site for glucagon on myocardial adenylate cyclase.", "contents": "Glucagon and adenylate cyclase: binding studies and requirements for activation. Solubilization of myocardial adenylate cyclase abolished responsiveness to glucagon and catecholamines, two of the hormones which activate the membrane-bound enzyme. Adenylate cyclase freed of detergent by DEAE-cellulose chromatography continues to remain unresponsive to hormone stimulation. However, adding purified bovine brain phospholipids--phosphotidylserine and monophosphatidylinositol--restored responsiveness to glucagon and catecholamines, respectively. 125-i-glucagon binding appeared to be independent of phospholipid, since equal binding was observed in the presence or absence of detergent and in the presence or absence of phospholipids. Chromatography of the solubilized preparation on Sephadex G-100 WAS CHARACTERIZED BY 125-I-glucagon binding and fluoride-stimulatable adenylate cyclase activity appearing in the fractions consistent with the void volume, suggesting a molecular weight greater than 100,000 for the receptor-adenylate cyclase complex. Prior incubation of the binding peak with 125-I-glucagon and rechromatography of the bound glucagon on Sephadex G-100 shifted its elution to a later fraction consistent with a smaller-molecular-weight peak. The molecular weight of this material was 24,000 to 28,000, as determined by SDS polyacrylamide gel electrophoresis. The latter findings are consistent with a dissociable receptor site for glucagon on myocardial adenylate cyclase."} {"id": "PMID:165690", "title": "Regulation of cyclic AMP content in normal and malignant brain cells.", "content": "Pharmacologic characterization of the neurotransmitter-sensitive cyclic AMP-second messenger systems of brain has proven to be a complex and difficult endeavor. At least two types of receptor appear to be involved in the mediation of the effects of NE on cyclic AMP content. One of these receptor systems appears to mediate the potentiation by NE of the effect of adenosine of cyclic AMP accumulation. The cellular heterogeneity of brain has retarded the determination of the mechanism underlying the synergistic interaction of catecholamines and adenosine. An attempt to use clonal cell lines to examine the action of NE and adenosine on cyclic AMP content has resulted in the demonstration that adenosine acts in a hormone-like fashion to stimulate adenylate cyclase activity. However, the studies did not shed light on the mechanism of synergism. An increasing number of reports are appearing which support the idea that the responsiveness of cells to neuronally released NE may involve adaptive changes in the responsiveness of the cyclic AMP-second messenger system which compensate for chronic over- or underproduction of the first messenger, NE. Evidence was presented that such a regulatory process may be operative in rat cerebral cortex. Our studies of catecholamine-induced loss of responsiveness in human astrocytoma cells have led us to the conclusion that the loss in the capacity of the cells to accumulate cyclic AMP is a result of a loss in the capacity to synthesize cyclic AMP. However, it is probable that different cells make use of different mechanisms (e.g., changes in phosphodiesterase activity) to regulate their ability to respond to hormones or neurotransmitters. The physiologic importance of this level of regulation of responsiveness to hormones is not known at this time.", "contents": "Regulation of cyclic AMP content in normal and malignant brain cells. Pharmacologic characterization of the neurotransmitter-sensitive cyclic AMP-second messenger systems of brain has proven to be a complex and difficult endeavor. At least two types of receptor appear to be involved in the mediation of the effects of NE on cyclic AMP content. One of these receptor systems appears to mediate the potentiation by NE of the effect of adenosine of cyclic AMP accumulation. The cellular heterogeneity of brain has retarded the determination of the mechanism underlying the synergistic interaction of catecholamines and adenosine. An attempt to use clonal cell lines to examine the action of NE and adenosine on cyclic AMP content has resulted in the demonstration that adenosine acts in a hormone-like fashion to stimulate adenylate cyclase activity. However, the studies did not shed light on the mechanism of synergism. An increasing number of reports are appearing which support the idea that the responsiveness of cells to neuronally released NE may involve adaptive changes in the responsiveness of the cyclic AMP-second messenger system which compensate for chronic over- or underproduction of the first messenger, NE. Evidence was presented that such a regulatory process may be operative in rat cerebral cortex. Our studies of catecholamine-induced loss of responsiveness in human astrocytoma cells have led us to the conclusion that the loss in the capacity of the cells to accumulate cyclic AMP is a result of a loss in the capacity to synthesize cyclic AMP. However, it is probable that different cells make use of different mechanisms (e.g., changes in phosphodiesterase activity) to regulate their ability to respond to hormones or neurotransmitters. The physiologic importance of this level of regulation of responsiveness to hormones is not known at this time."} {"id": "PMID:165701", "title": "Development of the implantation chamber in the pregnant bitch.", "content": "Uteri taken from 25 bitches at various times during the early stages of pregnancy were studies cytologically to determine how the implantation chamber developed and how fetal-maternal relations were established. On day 13 after the end of estrus, knobs of trophoblastic syncytium formed and became wedged between cells of the uterine luminal epithelium. The syncytium quickly spread along the uterine lumen and into the mouths of the glands, dislodging and surrounding maternal cells. As invasion continued trophoblastic villi, consisting of cores of cytotrophoblast covered by a continuous layer of syncytium, penetrated deeper into the endometrium. The syncytium spread to surround maternal vessels and decidual cells. By day 26 the trophoblast had extended down to the large lacunae. Here syncytial trophoblast covering tips of the villi degenerated, leaving cytotrophoblast exposed to the necrotic zone. These cells possessed characteristics of absorbing cells. Hematomas were formed by focal necrosis of fetal and endometrial tissue at the poles of the implantation sites. Large pools of extravasated blood accumulated and red blood cells were phagocytized by surrounding trophoblastic cells. Therefore, the endotheliochorial relationship in the canine placenta appeared to be established by syncytial trophoblast invading a cellular endometrium. In the necrotic zone and hematomas, cellular trophoblast may have lost its syncytial covering, but elsewhere maternal vessels and decidual cells in the placenta were in direct contact only with syncytial trophoblast.", "contents": "Development of the implantation chamber in the pregnant bitch. Uteri taken from 25 bitches at various times during the early stages of pregnancy were studies cytologically to determine how the implantation chamber developed and how fetal-maternal relations were established. On day 13 after the end of estrus, knobs of trophoblastic syncytium formed and became wedged between cells of the uterine luminal epithelium. The syncytium quickly spread along the uterine lumen and into the mouths of the glands, dislodging and surrounding maternal cells. As invasion continued trophoblastic villi, consisting of cores of cytotrophoblast covered by a continuous layer of syncytium, penetrated deeper into the endometrium. The syncytium spread to surround maternal vessels and decidual cells. By day 26 the trophoblast had extended down to the large lacunae. Here syncytial trophoblast covering tips of the villi degenerated, leaving cytotrophoblast exposed to the necrotic zone. These cells possessed characteristics of absorbing cells. Hematomas were formed by focal necrosis of fetal and endometrial tissue at the poles of the implantation sites. Large pools of extravasated blood accumulated and red blood cells were phagocytized by surrounding trophoblastic cells. Therefore, the endotheliochorial relationship in the canine placenta appeared to be established by syncytial trophoblast invading a cellular endometrium. In the necrotic zone and hematomas, cellular trophoblast may have lost its syncytial covering, but elsewhere maternal vessels and decidual cells in the placenta were in direct contact only with syncytial trophoblast."} {"id": "PMID:165702", "title": "Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes.", "content": "Developing lymph nodes from 30 human fetuses with crownrump lengths (CRL) of 38 mm (8.7 wk) to 245 mm (26 wk) were studied by light and electron microscopy. Blood vessels that appear to be postcapillary venules (PCV) are present in nodes of 47 mm CRL and older fetuses. These venules first appear in nodes whehn the nodal population of lymphocytes is sparse. In these early nodes PCV are distributed randomly and consist of a low endothelium, underlying basal lamina and incomplete pericyte sheath. Early nodal PCV are distinguised from other nodal blood vessels by the presence of lymphocyte diapedesis and several luminal lymphocytes. In the late stages of nodal development PCV are the more common non-capillary blood vessel and appear in the parenchyma near the periphery of the node. Late nodal PCV are generally characterized by a cuboidal endothelium that is rich in Golgi apparatus, lysosomes and Weibel-Palade bodies. The lumen and wall of late nodal PCV contain lymphocytes. The relationship between the development of the parenchyma of fetal nodes and the appearance and activity of PCV, the passage of lymphocytes through the PCV wall and the fine structure of developing PCV are described. It is suggested that the lymphocytes that first appear in developing nodes, and the majority of the lymphocytes found in late nodes, migrate to the node via the blood vascular system and enter the nodal parenchyma by passing across PCV endothelium.", "contents": "Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes. Developing lymph nodes from 30 human fetuses with crownrump lengths (CRL) of 38 mm (8.7 wk) to 245 mm (26 wk) were studied by light and electron microscopy. Blood vessels that appear to be postcapillary venules (PCV) are present in nodes of 47 mm CRL and older fetuses. These venules first appear in nodes whehn the nodal population of lymphocytes is sparse. In these early nodes PCV are distributed randomly and consist of a low endothelium, underlying basal lamina and incomplete pericyte sheath. Early nodal PCV are distinguised from other nodal blood vessels by the presence of lymphocyte diapedesis and several luminal lymphocytes. In the late stages of nodal development PCV are the more common non-capillary blood vessel and appear in the parenchyma near the periphery of the node. Late nodal PCV are generally characterized by a cuboidal endothelium that is rich in Golgi apparatus, lysosomes and Weibel-Palade bodies. The lumen and wall of late nodal PCV contain lymphocytes. The relationship between the development of the parenchyma of fetal nodes and the appearance and activity of PCV, the passage of lymphocytes through the PCV wall and the fine structure of developing PCV are described. It is suggested that the lymphocytes that first appear in developing nodes, and the majority of the lymphocytes found in late nodes, migrate to the node via the blood vascular system and enter the nodal parenchyma by passing across PCV endothelium."} {"id": "PMID:165703", "title": "Quantification of plasma cholesterol and triglyceride levels in hypercholesterolemic subjects receiving ascorbic acid supplements.", "content": "In order to assess the possible effects of ascorbic acid on plasma cholesterol and triglyceride levels and plasma lipoprotein composition, nine hypercholesterolemic subjects were treated with oral ascorbic acid (4 g/day) for 2 months. The data demonstrate: 1) no significant change in plasma cholesterol or triglyceride levels; 2) no significant change in the cholesterol or triglyceride concentrations of the major lipoprotein classes; and 3) the unexpected appearance of extra pre-beta bands on lipoprotein electrophoresis by the end of the ascorbic acid treatment period.", "contents": "Quantification of plasma cholesterol and triglyceride levels in hypercholesterolemic subjects receiving ascorbic acid supplements. In order to assess the possible effects of ascorbic acid on plasma cholesterol and triglyceride levels and plasma lipoprotein composition, nine hypercholesterolemic subjects were treated with oral ascorbic acid (4 g/day) for 2 months. The data demonstrate: 1) no significant change in plasma cholesterol or triglyceride levels; 2) no significant change in the cholesterol or triglyceride concentrations of the major lipoprotein classes; and 3) the unexpected appearance of extra pre-beta bands on lipoprotein electrophoresis by the end of the ascorbic acid treatment period."} {"id": "PMID:165704", "title": "Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders.", "content": "Recent studies have demonstrated that the human intestinal enzymes of carbohydrate digestion and metabolism can be regulated by dietary sugars. These studies have utilized direct assay of intestinal mucosal enzyme activity. Mucosa has been obtained by the use of peroral jejunal biopsy techniques which provide 10-15 mg of mucosa in a safe, simple and reproducible manner. Dietary sucrose, as compared to dietary glucose, increases the activities of the jejunal disaccharidases, sucrase and maltase, but not lactase. Fructose reproduces the sucrose effect and appears to be the active principle in the sucrose molecule. Lactose deprivation or lactose feeding does not alter lactase activity. Fructose has been useful in treating one patient with sucrase-isomaltase deficiency. Jejunal glycolytic enzyme activities are also regulated by dietary sugars. Certain enzymes are highest with specific dietary carbohydrates, lower with other sugars and lowest on a carbohydrate-free diet. The regulation of human jejunal glycolytic enzyme activity takes place in hours, whereas the change in disaccharidase activity occurs in 2-5 days. The mechanism of this regulation is not known. Additional investigations have shown that jejunal glycolytic enzyme activities but not the disaccharidases are controlled by oral folic acid as well. This effect occurs within 1 day also. The mechanism is unknown. Large doses of folate have been of benefit in a few patients with certain glycolytic enzyme deficiency states. Preliminary studies have demonstrated that selected patients with chronic undiagnosed intestinal disorders fail to manifest an adaptive response of their jejunal glycolytic enzyme activities to dietary sugars. This condition has been termed a \"maladaptation syndrome.\".", "contents": "Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders. Recent studies have demonstrated that the human intestinal enzymes of carbohydrate digestion and metabolism can be regulated by dietary sugars. These studies have utilized direct assay of intestinal mucosal enzyme activity. Mucosa has been obtained by the use of peroral jejunal biopsy techniques which provide 10-15 mg of mucosa in a safe, simple and reproducible manner. Dietary sucrose, as compared to dietary glucose, increases the activities of the jejunal disaccharidases, sucrase and maltase, but not lactase. Fructose reproduces the sucrose effect and appears to be the active principle in the sucrose molecule. Lactose deprivation or lactose feeding does not alter lactase activity. Fructose has been useful in treating one patient with sucrase-isomaltase deficiency. Jejunal glycolytic enzyme activities are also regulated by dietary sugars. Certain enzymes are highest with specific dietary carbohydrates, lower with other sugars and lowest on a carbohydrate-free diet. The regulation of human jejunal glycolytic enzyme activity takes place in hours, whereas the change in disaccharidase activity occurs in 2-5 days. The mechanism of this regulation is not known. Additional investigations have shown that jejunal glycolytic enzyme activities but not the disaccharidases are controlled by oral folic acid as well. This effect occurs within 1 day also. The mechanism is unknown. Large doses of folate have been of benefit in a few patients with certain glycolytic enzyme deficiency states. Preliminary studies have demonstrated that selected patients with chronic undiagnosed intestinal disorders fail to manifest an adaptive response of their jejunal glycolytic enzyme activities to dietary sugars. This condition has been termed a \"maladaptation syndrome.\"."} {"id": "PMID:165705", "title": "Cell membrane receptors for polypeptide hormones. Application to the study of disease states in mice, and men.", "content": "Recent studies have suggested that the first step in the action of polypeptide hormones and catecholamines is binding to surface membrane receptor sites. This interaction can be studied directly using radioactively labeled hormones and a variety of receptor preparations. With these radioreceptor assay technics, it has been possible to define structure-activity relationships and to assay plasma hormones. These studies have also been used to define alterations in the hormone receptors in disease that lead to peripheral resistance to hormonal action and to characterize the factors that regulate receptor concentrations.", "contents": "Cell membrane receptors for polypeptide hormones. Application to the study of disease states in mice, and men. Recent studies have suggested that the first step in the action of polypeptide hormones and catecholamines is binding to surface membrane receptor sites. This interaction can be studied directly using radioactively labeled hormones and a variety of receptor preparations. With these radioreceptor assay technics, it has been possible to define structure-activity relationships and to assay plasma hormones. These studies have also been used to define alterations in the hormone receptors in disease that lead to peripheral resistance to hormonal action and to characterize the factors that regulate receptor concentrations."} {"id": "PMID:165707", "title": "Comparisons of major cell-surface proteins of normal and transformed cells.", "content": "Transformation of the chick fibroblast surface has been studied in cells infected with Schmidt-Ruppin Rous sarcoma virus and the temperature-sensitive mutant of this virus, TS-68. Major findings following transformation induced by a shift from nonpermissive (41 C.) to permissive (36 C.) temperature in TS-68 infected cells were: (1) rapid cessation or slowing of the synthesis of a protein, M.W. 100-200,000, localization uncertain; (2) cessation or slowing of the synthesis of a plasma membrane protein, M.W. 45,000, within 2-4 hours; (3) cessation or slowing of the synthesis of a large trypsin- and collagenase- sensitive protein (M.W. greater than 200,000) only after an extended period of morphologic transformation. In addition, increased quantities of type-specific viral antigen in the membranes of infected cells were observed in TS-68-infected cells at 41 compared with 36 C.", "contents": "Comparisons of major cell-surface proteins of normal and transformed cells. Transformation of the chick fibroblast surface has been studied in cells infected with Schmidt-Ruppin Rous sarcoma virus and the temperature-sensitive mutant of this virus, TS-68. Major findings following transformation induced by a shift from nonpermissive (41 C.) to permissive (36 C.) temperature in TS-68 infected cells were: (1) rapid cessation or slowing of the synthesis of a protein, M.W. 100-200,000, localization uncertain; (2) cessation or slowing of the synthesis of a plasma membrane protein, M.W. 45,000, within 2-4 hours; (3) cessation or slowing of the synthesis of a large trypsin- and collagenase- sensitive protein (M.W. greater than 200,000) only after an extended period of morphologic transformation. In addition, increased quantities of type-specific viral antigen in the membranes of infected cells were observed in TS-68-infected cells at 41 compared with 36 C."} {"id": "PMID:165709", "title": "Composition of membranes of cells transformed by tumorigenic DNA and RNA viruses.", "content": "Continuous cell lines obtained from mouse and hamster embryonic tissue and human lung contain a homologous series of acidic glycolipids known as gangliosides. These complex lipids are highly concentrated in plasma cell membranes. The ganglioside pattern becomes greatly simplified when cells are transformed by tumorigenic DNA and RNA viruses. Non-transforming viruses and lytic infection of cells by tumorigenic viruses without neoplastic tranformation do not cause changes in gangliosides. The alterations of ganglioside composition are the result of specific blocks in the biosynthesis of these lipids. The significance of these impairments of membrane glycolipid formation and the nature of the regulatory site(s) involved are considered with regard to the altered social behavior of transformed cells.", "contents": "Composition of membranes of cells transformed by tumorigenic DNA and RNA viruses. Continuous cell lines obtained from mouse and hamster embryonic tissue and human lung contain a homologous series of acidic glycolipids known as gangliosides. These complex lipids are highly concentrated in plasma cell membranes. The ganglioside pattern becomes greatly simplified when cells are transformed by tumorigenic DNA and RNA viruses. Non-transforming viruses and lytic infection of cells by tumorigenic viruses without neoplastic tranformation do not cause changes in gangliosides. The alterations of ganglioside composition are the result of specific blocks in the biosynthesis of these lipids. The significance of these impairments of membrane glycolipid formation and the nature of the regulatory site(s) involved are considered with regard to the altered social behavior of transformed cells."} {"id": "PMID:165710", "title": "Multilamellar cytosomes in a particular form of late-infantile amaurotic idiocy.", "content": "There is a particular form of late-infantile amaurotic idiocy in which no clear chemical-pathological or unique enzyme abnormalities have been identified to date. A distinctive morphological feature has been recognized on electron microscopical examination of tissues from these patients, which has been descriptively labeled with various terms, including \"multilamellar cytosomes\" (MLC). Illustrations of MLC in a patient with this late-infantile form of cerebroretinal degeneration show their reactivity with the periodic acid-silver methenamine reaction for glycoproteins. The MLC are shown to be morphologically identical in cerebral tissue obtained at biopsy, in the same tissue obtained three years later at autopsy, and in skeletal muscle.", "contents": "Multilamellar cytosomes in a particular form of late-infantile amaurotic idiocy. There is a particular form of late-infantile amaurotic idiocy in which no clear chemical-pathological or unique enzyme abnormalities have been identified to date. A distinctive morphological feature has been recognized on electron microscopical examination of tissues from these patients, which has been descriptively labeled with various terms, including \"multilamellar cytosomes\" (MLC). Illustrations of MLC in a patient with this late-infantile form of cerebroretinal degeneration show their reactivity with the periodic acid-silver methenamine reaction for glycoproteins. The MLC are shown to be morphologically identical in cerebral tissue obtained at biopsy, in the same tissue obtained three years later at autopsy, and in skeletal muscle."} {"id": "PMID:165714", "title": "Effects of gastrointestinal hormones on vascular smooth muscle.", "content": "The effects of the gastrointestinal hormones secretin and cholecystokinin (CCK) were investigated on rat portal-vein mechanical activity. Doses of 0.03-0.60 units/ml Boots secretin; 0.18-0.60 units/ml pure, natural secretin; and 0.12-0.60 units/ml CCK elicited dose-dependent decreases in amplitude and simultaneous increases in frequency of spontaneous contractions that were unaffected by alpha-or beta-adrenergic or cholinergic blocdade. These effects were mimicked by isoproterenol, theophylline, and cyclic AMP, and all agents tested were also effective in reducing K-or norepinephrine-induced tension. Additionally, subthreshold doses of CCK and secretin elicited responses when given in combination, and the effects of the hormomes at all doses were potentiated by theophyline, indicating an interaction berween these hormones on rat portal vein thatmay involve cyclic AMP. It is suggested that part of the mechanism of hormone-induced mesenteric vasodilatation may involve a direct relaxing effect of the hormones on vascularsmooth muscle.", "contents": "Effects of gastrointestinal hormones on vascular smooth muscle. The effects of the gastrointestinal hormones secretin and cholecystokinin (CCK) were investigated on rat portal-vein mechanical activity. Doses of 0.03-0.60 units/ml Boots secretin; 0.18-0.60 units/ml pure, natural secretin; and 0.12-0.60 units/ml CCK elicited dose-dependent decreases in amplitude and simultaneous increases in frequency of spontaneous contractions that were unaffected by alpha-or beta-adrenergic or cholinergic blocdade. These effects were mimicked by isoproterenol, theophylline, and cyclic AMP, and all agents tested were also effective in reducing K-or norepinephrine-induced tension. Additionally, subthreshold doses of CCK and secretin elicited responses when given in combination, and the effects of the hormomes at all doses were potentiated by theophyline, indicating an interaction berween these hormones on rat portal vein thatmay involve cyclic AMP. It is suggested that part of the mechanism of hormone-induced mesenteric vasodilatation may involve a direct relaxing effect of the hormones on vascularsmooth muscle."} {"id": "PMID:165715", "title": "Cholagiocarcinoma in a patient previously given thorotrast.", "content": "The long-term effects of thorotrast administration include local granulomas, blood cell abnormalities, and cancer. To date, more than 100 cases of liver cancer have been reported in patients previously given this radioactive contrast material, with a latency period of approximately 22 years. We report such a case; the patient not only had a thorotrast-induced cholangiocarcinoma, but also showed striking morphologic changes in the red blood cells secondary to splenic dysfunction.", "contents": "Cholagiocarcinoma in a patient previously given thorotrast. The long-term effects of thorotrast administration include local granulomas, blood cell abnormalities, and cancer. To date, more than 100 cases of liver cancer have been reported in patients previously given this radioactive contrast material, with a latency period of approximately 22 years. We report such a case; the patient not only had a thorotrast-induced cholangiocarcinoma, but also showed striking morphologic changes in the red blood cells secondary to splenic dysfunction."} {"id": "PMID:165716", "title": "Crohn's disease of the colon. III. Toxic dilatation of the colon in Crohn's colitis.", "content": "In a group of 160 patients with Crohn's disease involving the colon, there were seven patients with toxic dilatation, four with granulomatous colitis and three with ileocolitis, all successfully treated without mortality. This complications is more common than previously recognized in Crohn's colitis. In Crohn's disease, toxic dilatation is less likely to proceed to perforation of the bowel, because of the nature of the pathology and is more likely to respond to conservative measures: intubation, with decompression, corticotropin, steroids and high-dose antibiotic administration. Although patients do recover from this life-threatening complication with conservative management, the majority of patients, if not all, will ultimately come to surgical excision of the colon. If surgery is mandatory, it should be carried out early, rather than late, in the patient who is failing to respond to medical therapy, certainly before the development of perforation, massive hemorrhage, or gram negative sepsis with shock. The surgical therapy will depend upon the state of the bowel at laparotomy. Thus, an intact bowel in a young patient, would favor subtotal colectomy or proctocolectomy; a sealed perforation, a diverting ileostomy with skin level colostomy decompression as suggested by Turnbull and a free perforation, the minimum adequate procedure which will tide the patient over the early postoperative period. Diverting ileostomy alone has been effective in two of our patients but should be avoided in ulcerative colitis. The critically ill patient with the ominous finding of \"disintegrating colitis\" and multiple leaks, will require nothing less than total radical excision of the diseased bowel in the hope of immediate salvage.", "contents": "Crohn's disease of the colon. III. Toxic dilatation of the colon in Crohn's colitis. In a group of 160 patients with Crohn's disease involving the colon, there were seven patients with toxic dilatation, four with granulomatous colitis and three with ileocolitis, all successfully treated without mortality. This complications is more common than previously recognized in Crohn's colitis. In Crohn's disease, toxic dilatation is less likely to proceed to perforation of the bowel, because of the nature of the pathology and is more likely to respond to conservative measures: intubation, with decompression, corticotropin, steroids and high-dose antibiotic administration. Although patients do recover from this life-threatening complication with conservative management, the majority of patients, if not all, will ultimately come to surgical excision of the colon. If surgery is mandatory, it should be carried out early, rather than late, in the patient who is failing to respond to medical therapy, certainly before the development of perforation, massive hemorrhage, or gram negative sepsis with shock. The surgical therapy will depend upon the state of the bowel at laparotomy. Thus, an intact bowel in a young patient, would favor subtotal colectomy or proctocolectomy; a sealed perforation, a diverting ileostomy with skin level colostomy decompression as suggested by Turnbull and a free perforation, the minimum adequate procedure which will tide the patient over the early postoperative period. Diverting ileostomy alone has been effective in two of our patients but should be avoided in ulcerative colitis. The critically ill patient with the ominous finding of \"disintegrating colitis\" and multiple leaks, will require nothing less than total radical excision of the diseased bowel in the hope of immediate salvage."} {"id": "PMID:165718", "title": "The sudden infant death syndrome and epidemic viral disease.", "content": "A study was done to investigate the relationship between the sudden infant death syndrome (SIDS) and epidemic respiratory viral disease among hospitalized children under 18 months of age. During the 42 month-period of this study, there were 778 sudden infant deaths in Chicago and 3244 hospital admissions of children under 18 months for respiratory disease. Four outbreaks of respiratory syncytial (RS) virus infections, three outbreaks of influenza A virus infections, and several small clusters of parainfluenza virus infections occurred during the course of this study. Influenza A was the only virus infection found to have a statistically significant association with SIDS. Although environmental temperature was also significantly correlated with SIDS, the association with influenza A virus infection was independent of this temperature effect and neither association was strong.", "contents": "The sudden infant death syndrome and epidemic viral disease. A study was done to investigate the relationship between the sudden infant death syndrome (SIDS) and epidemic respiratory viral disease among hospitalized children under 18 months of age. During the 42 month-period of this study, there were 778 sudden infant deaths in Chicago and 3244 hospital admissions of children under 18 months for respiratory disease. Four outbreaks of respiratory syncytial (RS) virus infections, three outbreaks of influenza A virus infections, and several small clusters of parainfluenza virus infections occurred during the course of this study. Influenza A was the only virus infection found to have a statistically significant association with SIDS. Although environmental temperature was also significantly correlated with SIDS, the association with influenza A virus infection was independent of this temperature effect and neither association was strong."} {"id": "PMID:165719", "title": "Serologic characterization and sero-epidemiologic studies on acute hemorrhagic conjunctivitis (AHC) virus.", "content": "Serologic and sero-epidemiologic characteristics of AHC virus infection were studied by neutralization test (NT). Four-fold or greater virus neutralizing (VN) antibody response was demonstrated to the Japanese isolate of AHC virus (the J 670/71 strain) in 77.3% and 66.7% of paired sera from clinical AHC patients in Japan (1971-1973) and Tunisia (1973). The four patients from Indonesia studied in 1972 showed similar antibody response. Cross-neutralization tests of AHC virus isolated in Japan (1971), Taiwan (1971), Hong Kong (1971), Thailand (1972), Indonesia (1972), Singapore (1972), Morocco (1971) and England (1971) with three kinds of antisera prepared against Japanese, Hong Kong and Moroccan AHC virus isolates indicated their antigenic identity. However, isolates from Sinapore in 1970 (Singapore 70 virus) were not neutralized with the AHC virus antisera mentioned above: Singapore 70 virus constitutes another antigenic type, to which, however, no VN antibody rise was found in paired patients' sera from Japan, Tunisia and Indonesia. Thus, no serologic evidence supporting an etiologic role of this virus group in the development of AHC was found. Although cross-tests using monospecific antisera suggested some cross-relation between AHC and both echovirus type 4 (E4) and coxsackie A (CA), type 19, no serologic relationship between AHC and these viruses was found. Sera from healthy individuals collected before and after AHC outbreaks were tested for VN antibody against AHC virus in Japan and two epidemic foci, Ghana and Indonesia. Before the epidemic, 80 to 90% of the people lacked antibody in the three countries, but 39.7% and 45.2% of inhabitants posessed VN antibody of 1:8 or over in Ghana and Indonesia after the outbreak. In Japan, however, only a slight increase was found in VN antibody prevalence afterwards. Serologic study showed that 41.5% of horse sera were VN positive at dilutions of 1:8 or more; many cattle sera also had a low VN titer but few cynomologus monkey sera had VN activity.", "contents": "Serologic characterization and sero-epidemiologic studies on acute hemorrhagic conjunctivitis (AHC) virus. Serologic and sero-epidemiologic characteristics of AHC virus infection were studied by neutralization test (NT). Four-fold or greater virus neutralizing (VN) antibody response was demonstrated to the Japanese isolate of AHC virus (the J 670/71 strain) in 77.3% and 66.7% of paired sera from clinical AHC patients in Japan (1971-1973) and Tunisia (1973). The four patients from Indonesia studied in 1972 showed similar antibody response. Cross-neutralization tests of AHC virus isolated in Japan (1971), Taiwan (1971), Hong Kong (1971), Thailand (1972), Indonesia (1972), Singapore (1972), Morocco (1971) and England (1971) with three kinds of antisera prepared against Japanese, Hong Kong and Moroccan AHC virus isolates indicated their antigenic identity. However, isolates from Sinapore in 1970 (Singapore 70 virus) were not neutralized with the AHC virus antisera mentioned above: Singapore 70 virus constitutes another antigenic type, to which, however, no VN antibody rise was found in paired patients' sera from Japan, Tunisia and Indonesia. Thus, no serologic evidence supporting an etiologic role of this virus group in the development of AHC was found. Although cross-tests using monospecific antisera suggested some cross-relation between AHC and both echovirus type 4 (E4) and coxsackie A (CA), type 19, no serologic relationship between AHC and these viruses was found. Sera from healthy individuals collected before and after AHC outbreaks were tested for VN antibody against AHC virus in Japan and two epidemic foci, Ghana and Indonesia. Before the epidemic, 80 to 90% of the people lacked antibody in the three countries, but 39.7% and 45.2% of inhabitants posessed VN antibody of 1:8 or over in Ghana and Indonesia after the outbreak. In Japan, however, only a slight increase was found in VN antibody prevalence afterwards. Serologic study showed that 41.5% of horse sera were VN positive at dilutions of 1:8 or more; many cattle sera also had a low VN titer but few cynomologus monkey sera had VN activity."} {"id": "PMID:165720", "title": "Serologic profile of children in a Mexican highland community: prevalence of complement-fixing antibodies to Mycoplasma pneumoniae, respiratory syncytial virus and parainfluenza viruses.", "content": "The study investigated the prevalence of antibodies to five leading agents of childhood respiratory disease in the county of Huixquilucan, Mexico. Tests of sera from a random sample of children between 3 months and 18 years of age confirmed serologically the presence of Mycoplasma pneumoniae, respiratory syncytial (RS) virus and parainfluenza 1, 2 and 3 viruses in this relatively isolated highland community. Highest overall antibody frequency of 64.2% was seen for parainfluenza 3, and antibody to this virus was acquired early in life. Antibody to M. pneumoniae was least prevalent among children surveyed; this rate was 15.5% overall. This was only slightly below the prevalence rates for antibodies to RS virus and parainfluenza 1 and 2 viruses, which had intermediate frequency rates of 23%, 32%, and 22.9%, respectively. The relatively low prevalence of antibody to RS virus was unexpected. Differences in prevalence rates in regard to location of residence or family size were insignificant. Statistically significant differences in age-specific antibody prevalence rates in respect to sex were noted only for the 5- to 9-year-old group to M. pneumoniae and to parainfluenza 3.", "contents": "Serologic profile of children in a Mexican highland community: prevalence of complement-fixing antibodies to Mycoplasma pneumoniae, respiratory syncytial virus and parainfluenza viruses. The study investigated the prevalence of antibodies to five leading agents of childhood respiratory disease in the county of Huixquilucan, Mexico. Tests of sera from a random sample of children between 3 months and 18 years of age confirmed serologically the presence of Mycoplasma pneumoniae, respiratory syncytial (RS) virus and parainfluenza 1, 2 and 3 viruses in this relatively isolated highland community. Highest overall antibody frequency of 64.2% was seen for parainfluenza 3, and antibody to this virus was acquired early in life. Antibody to M. pneumoniae was least prevalent among children surveyed; this rate was 15.5% overall. This was only slightly below the prevalence rates for antibodies to RS virus and parainfluenza 1 and 2 viruses, which had intermediate frequency rates of 23%, 32%, and 22.9%, respectively. The relatively low prevalence of antibody to RS virus was unexpected. Differences in prevalence rates in regard to location of residence or family size were insignificant. Statistically significant differences in age-specific antibody prevalence rates in respect to sex were noted only for the 5- to 9-year-old group to M. pneumoniae and to parainfluenza 3."} {"id": "PMID:165721", "title": "Progress in hepatitis research.", "content": "A brief account of recent developments and current nomenclature regarding the viral agents of hepatitis A and B is presented.", "contents": "Progress in hepatitis research. A brief account of recent developments and current nomenclature regarding the viral agents of hepatitis A and B is presented."} {"id": "PMID:165723", "title": "Physiologic significance of 17beta-estradiol binding in the rabbit Fallopian tube.", "content": "Rabbit Fallopian tube contractility was recorded in vitro during perfusion with either Locke's solution or that solution containing CN-55, 945-27 (CN; or CI-628), a nonsteroidal estrogen antagonist (Endocrinology 79: 153, 1966). Contractility was inhibited and 17beta-estradiol (E2) displaced from both its cytoplasmic (8S) and nuclear (4S) receptors in the presence of the above agent. These effects result from a direct interaction between CN and the E2-receptor complexes. Two types of evidence show the specificity of the foregoing responses: (1) nonspecific binding of E2 to serum proteins was unaffected by the antagonist and (2) CN had no effect on contractility of a nontarget tissue, i.e., rabbit ileum. In addition, Fallopian tube contractions induced by strong electrical stimulation of K-depolarized tissues (i.e., in the absence of normal ionic gradients) were inhibited by CN and a decrease in the binding capacities of 8S and 4S receptors was again observed. Thus, antagonism of specific E2 binding inhibits the contractile mechanism at a level other than the cell membrane. These observations, and additional findings concerning the reversibility of CN action, indicate that E2 binding is essential for contractility of the rabbit Fallopian tube.", "contents": "Physiologic significance of 17beta-estradiol binding in the rabbit Fallopian tube. Rabbit Fallopian tube contractility was recorded in vitro during perfusion with either Locke's solution or that solution containing CN-55, 945-27 (CN; or CI-628), a nonsteroidal estrogen antagonist (Endocrinology 79: 153, 1966). Contractility was inhibited and 17beta-estradiol (E2) displaced from both its cytoplasmic (8S) and nuclear (4S) receptors in the presence of the above agent. These effects result from a direct interaction between CN and the E2-receptor complexes. Two types of evidence show the specificity of the foregoing responses: (1) nonspecific binding of E2 to serum proteins was unaffected by the antagonist and (2) CN had no effect on contractility of a nontarget tissue, i.e., rabbit ileum. In addition, Fallopian tube contractions induced by strong electrical stimulation of K-depolarized tissues (i.e., in the absence of normal ionic gradients) were inhibited by CN and a decrease in the binding capacities of 8S and 4S receptors was again observed. Thus, antagonism of specific E2 binding inhibits the contractile mechanism at a level other than the cell membrane. These observations, and additional findings concerning the reversibility of CN action, indicate that E2 binding is essential for contractility of the rabbit Fallopian tube."} {"id": "PMID:165724", "title": "Intracellular Treponema pallidum in cells of a syphilitic lesion of the uterine cervix.", "content": "In an electron microscopic study of biopsy tissue from an ulcer of the human cervix uteri, organisms morphologically identical to T. pallidum were observed. Large numbers of the organisms were seen lying among collagen fibrils and between cells. T. pallidum was seen within vacuoles of some fibroblasts and epithelial cells. Within the nucleoplasm of several cells, treponemes were observed, surrounded by a clear zone which might represent a mucopolysaccharide outer layer. The siameter of the organisms was 171 nm., and the diameter of the external axial filaments was 25 nm., dimensions similar to those reported by others for T. pallidum.", "contents": "Intracellular Treponema pallidum in cells of a syphilitic lesion of the uterine cervix. In an electron microscopic study of biopsy tissue from an ulcer of the human cervix uteri, organisms morphologically identical to T. pallidum were observed. Large numbers of the organisms were seen lying among collagen fibrils and between cells. T. pallidum was seen within vacuoles of some fibroblasts and epithelial cells. Within the nucleoplasm of several cells, treponemes were observed, surrounded by a clear zone which might represent a mucopolysaccharide outer layer. The siameter of the organisms was 171 nm., and the diameter of the external axial filaments was 25 nm., dimensions similar to those reported by others for T. pallidum."} {"id": "PMID:165722", "title": "Infectious mononucleosis preceding acute myelomonocytic leukemia.", "content": "The patient discussed in this report had acute myelomonocytic leukemia (AMML) associated with infectious mononucleosis. Infectious mononucleosis (IM) in association with acute leukemia (AL) has provided clinical investigators an active area of speculation for several years. Nineteen cases are presented for review in Table 1. The present case represents the second case of AMML to be associated with IM. It is the first case of a granulocytic leukemia reported in which active IM is occurring simultaneously with the onset of AL. Also, it represents the first case of associated IM-AL in which the diagnosis of IM is supported by lymphocyte culture data. This may represent a mechanism for additional investigation in future cases.", "contents": "Infectious mononucleosis preceding acute myelomonocytic leukemia. The patient discussed in this report had acute myelomonocytic leukemia (AMML) associated with infectious mononucleosis. Infectious mononucleosis (IM) in association with acute leukemia (AL) has provided clinical investigators an active area of speculation for several years. Nineteen cases are presented for review in Table 1. The present case represents the second case of AMML to be associated with IM. It is the first case of a granulocytic leukemia reported in which active IM is occurring simultaneously with the onset of AL. Also, it represents the first case of associated IM-AL in which the diagnosis of IM is supported by lymphocyte culture data. This may represent a mechanism for additional investigation in future cases."} {"id": "PMID:165725", "title": "Skeletal muscle respiratory capacity, endurance, and glycogen utilization.", "content": "This study was undertaken to evaluate the relationship between physical performance capacity and the mitochondrial content of skeletal muscle. Four groups of rats were trained by means of treadmill running 5 days/wk for 13 wk. One group ran 10 min/day, a second group ran 30 min/day, a third group ran 60 min/day, and a fourth group ran 120 min/day. The magnitude of the exercise-induced adaptive increase in gastrocnemius muscle respiratory capacity varied over a twofold range in the four groups. There were significant correlations between the levels of three mitochondrial markers (cytochrome c, citrate synthase, respiratory capacity) in the animals' gastrocnemius muscles and the duration of a run to exhaustion. There was also a significant correlation between the amounts of glycogen remaining in liver and skeletal muscle after a 30-min-long exercise test and the respiratory capacity of the animal's leg muscles. These findings are compatible with the interpretation that a close relationshiop exists between skeletal muscle mitochondrial content and the capacity to perform endurance exercise.", "contents": "Skeletal muscle respiratory capacity, endurance, and glycogen utilization. This study was undertaken to evaluate the relationship between physical performance capacity and the mitochondrial content of skeletal muscle. Four groups of rats were trained by means of treadmill running 5 days/wk for 13 wk. One group ran 10 min/day, a second group ran 30 min/day, a third group ran 60 min/day, and a fourth group ran 120 min/day. The magnitude of the exercise-induced adaptive increase in gastrocnemius muscle respiratory capacity varied over a twofold range in the four groups. There were significant correlations between the levels of three mitochondrial markers (cytochrome c, citrate synthase, respiratory capacity) in the animals' gastrocnemius muscles and the duration of a run to exhaustion. There was also a significant correlation between the amounts of glycogen remaining in liver and skeletal muscle after a 30-min-long exercise test and the respiratory capacity of the animal's leg muscles. These findings are compatible with the interpretation that a close relationshiop exists between skeletal muscle mitochondrial content and the capacity to perform endurance exercise."} {"id": "PMID:165726", "title": "Hypothalamic cells in an area mediating ACTH release respond to right atrial stretch.", "content": "The right atrium has been shown to mediate release of ACTH in response to small hemorrhage. Therefore, we sought to identify hypothalamic neurons (cat, alpha-choloralose 35-45 mg/kg) wholse firing rates were modulated by stretch of the right atrial-vena caval junction. Stretch was produced by intermittent inflation of a balloon implanted between the pericardium and the right atrium. In some cases, carotid arteries were occluded bilaterally. Previous results indicate that electrical stimulation of the medial-dorsal hypothalamus (MDH) causes prompt changes in ACTH, but stimulation in the lateral hypothalamus does not cause changes. Of 64 cells recorded in the MDH, 41 responded to atrial stretch. However, only 2 of 18 cells outside this region responded. Six cells were studied with and without carotid occlusion. Their response was dimished or absent in the absence of carotid occlusion. The results suggest that integration of afferent signals from cardiovascular receptors occurs in the MDH and that the MDH may participate in neural mediation of ACTH in response to hemodynamic changes.", "contents": "Hypothalamic cells in an area mediating ACTH release respond to right atrial stretch. The right atrium has been shown to mediate release of ACTH in response to small hemorrhage. Therefore, we sought to identify hypothalamic neurons (cat, alpha-choloralose 35-45 mg/kg) wholse firing rates were modulated by stretch of the right atrial-vena caval junction. Stretch was produced by intermittent inflation of a balloon implanted between the pericardium and the right atrium. In some cases, carotid arteries were occluded bilaterally. Previous results indicate that electrical stimulation of the medial-dorsal hypothalamus (MDH) causes prompt changes in ACTH, but stimulation in the lateral hypothalamus does not cause changes. Of 64 cells recorded in the MDH, 41 responded to atrial stretch. However, only 2 of 18 cells outside this region responded. Six cells were studied with and without carotid occlusion. Their response was dimished or absent in the absence of carotid occlusion. The results suggest that integration of afferent signals from cardiovascular receptors occurs in the MDH and that the MDH may participate in neural mediation of ACTH in response to hemodynamic changes."} {"id": "PMID:165727", "title": "Regulation of liver diphosphofructose phosphatase of the rat and hamster.", "content": "The regulatory properties of D-fructose-1, 6-diphosphate 1-phosphohydrolase (FDPase, EC 3.1.3.11) derived from livers of the albino rat and the golden Syrian hamster have been studies. The comparative analysis of the kinetics of saturation by fructose-1, l-diphosphate (FDP) and inhibition by FDP and by the allosteric ligand adenosine 5'-monophosphate (AMP) revealed differences that may have physiological implications. The inhibition studies pointed out that liver phosphatase is under a significantly less stringent regulation in the hibernating rodent. The concentration of AMP required to produce a 50 percent inhibition was 549.5 muM at 37 degrees C, 21.4 muM at 10 degrees C, and 9.2 muM at 5 percent C for the rat; 1,122 muM at 37 degrees C, 34.3 muM at 10 degrees C, and 20.4 muM at 5 degrees C for the hamster. Urea (0.67 M) simulates the effect of low temperature, potentiating the AMP inhibition. At 5 degrees C and 4 M urea, 75 percent loss of activity was found for the rat FDPase in contrast to a 25 percent loss for the hamster. At 37 degrees C, 4 M urea had practically no effect on the FDPase of both species.", "contents": "Regulation of liver diphosphofructose phosphatase of the rat and hamster. The regulatory properties of D-fructose-1, 6-diphosphate 1-phosphohydrolase (FDPase, EC 3.1.3.11) derived from livers of the albino rat and the golden Syrian hamster have been studies. The comparative analysis of the kinetics of saturation by fructose-1, l-diphosphate (FDP) and inhibition by FDP and by the allosteric ligand adenosine 5'-monophosphate (AMP) revealed differences that may have physiological implications. The inhibition studies pointed out that liver phosphatase is under a significantly less stringent regulation in the hibernating rodent. The concentration of AMP required to produce a 50 percent inhibition was 549.5 muM at 37 degrees C, 21.4 muM at 10 degrees C, and 9.2 muM at 5 percent C for the rat; 1,122 muM at 37 degrees C, 34.3 muM at 10 degrees C, and 20.4 muM at 5 degrees C for the hamster. Urea (0.67 M) simulates the effect of low temperature, potentiating the AMP inhibition. At 5 degrees C and 4 M urea, 75 percent loss of activity was found for the rat FDPase in contrast to a 25 percent loss for the hamster. At 37 degrees C, 4 M urea had practically no effect on the FDPase of both species."} {"id": "PMID:165728", "title": "Afferent aortic nerve fibers with their pathways in cardiac sympathetic nerves.", "content": "The effect of mechanical and chemical stimulation on activity of afferent aortic nerve fibers with pathways in the cardiac sympathetic nerves has been examined. Action potentials were derived from the second or third thoracic communicating ramus of the left side of anesthetized dogs. Thirty myelinated and 19 unmyelinated fibers responded to tapping the ascending aorta, aortic arch, and descending aorta. Both groups of fibers also responded to a rise as well as to a fall in aortic pressure. Spontaneous discharge of myelinated fibers was related to aortic pressure pulse whereas that of unmyelinated fibers was related to respiration. Asphyxia caused excitation of unmyelinated fibers but not of myelinated fibers. Both groups of fibers responded to topical application of lactic acid. Mechanical and chemical stimulation of the aorta after vagotomy caused a rise in systemic blood pressure and extension of the limbs. The results indicate the existence of afferent aortic fibers in the cardiac sympathetic nerves that cause circulatory and somatic responses.", "contents": "Afferent aortic nerve fibers with their pathways in cardiac sympathetic nerves. The effect of mechanical and chemical stimulation on activity of afferent aortic nerve fibers with pathways in the cardiac sympathetic nerves has been examined. Action potentials were derived from the second or third thoracic communicating ramus of the left side of anesthetized dogs. Thirty myelinated and 19 unmyelinated fibers responded to tapping the ascending aorta, aortic arch, and descending aorta. Both groups of fibers also responded to a rise as well as to a fall in aortic pressure. Spontaneous discharge of myelinated fibers was related to aortic pressure pulse whereas that of unmyelinated fibers was related to respiration. Asphyxia caused excitation of unmyelinated fibers but not of myelinated fibers. Both groups of fibers responded to topical application of lactic acid. Mechanical and chemical stimulation of the aorta after vagotomy caused a rise in systemic blood pressure and extension of the limbs. The results indicate the existence of afferent aortic fibers in the cardiac sympathetic nerves that cause circulatory and somatic responses."} {"id": "PMID:165729", "title": "Reduced nicotinamide adenine dinucleotide and depolarization in neurons.", "content": "Activity of frog dorsal root ganglion neurons, evoked by dorsal root stimulation under aerobic conditions, produced a change in the level of reduced nicotinamide adenine dinucleotide (NADH) on the surface of this tissue. There was a decrease of NADH (oxidation), followed by an increase of NADH (reduction). Both changes were dependent on previous activity, and a critical time is required in order to observe a similar response. At the frequency and duration of stimulation used here, each stimulus evoked neuron depolarization as shown by recording from single cells. The NADH oxidation occurred in the respiratory chain and it was selectively blocked by Amytal. The NAD reduction was attributed to 3-phosphoglyceraldehyde dehydrogenase activity and it was blocked by iodoacetate. The NADH oxidation and NAD reduction were attributed to respiratory chain activity and aerobic glycolysis, both activated and deactivated by changes of phosphate potential (ATP/ADP + Pi). A low phosphate potential activates the respiratory chain and glycolysis; a high phosphate potential deactivates the respiratory chain and glycolysis.", "contents": "Reduced nicotinamide adenine dinucleotide and depolarization in neurons. Activity of frog dorsal root ganglion neurons, evoked by dorsal root stimulation under aerobic conditions, produced a change in the level of reduced nicotinamide adenine dinucleotide (NADH) on the surface of this tissue. There was a decrease of NADH (oxidation), followed by an increase of NADH (reduction). Both changes were dependent on previous activity, and a critical time is required in order to observe a similar response. At the frequency and duration of stimulation used here, each stimulus evoked neuron depolarization as shown by recording from single cells. The NADH oxidation occurred in the respiratory chain and it was selectively blocked by Amytal. The NAD reduction was attributed to 3-phosphoglyceraldehyde dehydrogenase activity and it was blocked by iodoacetate. The NADH oxidation and NAD reduction were attributed to respiratory chain activity and aerobic glycolysis, both activated and deactivated by changes of phosphate potential (ATP/ADP + Pi). A low phosphate potential activates the respiratory chain and glycolysis; a high phosphate potential deactivates the respiratory chain and glycolysis."} {"id": "PMID:165730", "title": "Effects of thyroid hormone administration on skeletal muscle mitochondria.", "content": "The effects of thyroid hormone administration on the levels of a number of mitochondrial markers were measured in skeletal muscle and liver of normal rats. Injection of 18 mug of L-thyroxine (T4) per 100 g body wt every 4th day for 3 wk had no effect on the concentrations of cytochrome c, on citrate synthase activity, or on respiratory capacity of skeletal muscle. Injection of 200 mug of L-triiodothyronine (T3) daily for 5 days, or feeding 23 mg T4 and 7 mg T3/kg of diet for 2 wk, resulted in thyrotoxicosis and large increases in the activity of hepatic alpha-glycerophosphate dehydrogenase and other mitochondrial markers; however, the levels of activity of mitochondrial marker enzymes in gastrocnemius and quadriceps muscles were not significantly changed. Only when rats were fed 3 mg T4 and 1 mg T3/kg diet for a 6-wk period did we observe an increase in skeletal muscle mitochondrial markers. Thus, thyroxine treatment must be sufficiently prolonged if it is to be used as a tool for studying skeletal muscle mitochondrial biogenesis.", "contents": "Effects of thyroid hormone administration on skeletal muscle mitochondria. The effects of thyroid hormone administration on the levels of a number of mitochondrial markers were measured in skeletal muscle and liver of normal rats. Injection of 18 mug of L-thyroxine (T4) per 100 g body wt every 4th day for 3 wk had no effect on the concentrations of cytochrome c, on citrate synthase activity, or on respiratory capacity of skeletal muscle. Injection of 200 mug of L-triiodothyronine (T3) daily for 5 days, or feeding 23 mg T4 and 7 mg T3/kg of diet for 2 wk, resulted in thyrotoxicosis and large increases in the activity of hepatic alpha-glycerophosphate dehydrogenase and other mitochondrial markers; however, the levels of activity of mitochondrial marker enzymes in gastrocnemius and quadriceps muscles were not significantly changed. Only when rats were fed 3 mg T4 and 1 mg T3/kg diet for a 6-wk period did we observe an increase in skeletal muscle mitochondrial markers. Thus, thyroxine treatment must be sufficiently prolonged if it is to be used as a tool for studying skeletal muscle mitochondrial biogenesis."} {"id": "PMID:165731", "title": "Arterial water, cations, and norepinephrine in early and late renovascular hypertension.", "content": "In dogs made hypertensive renal artery stenosis and contralateral nephrectomy, the arterial and myocardial tissue content of water, cations (sodium, potassium, magnesium, calcium), and norepinephrine was measured 20 and 60 days after the operation. Hypertensive animals autopsied at the earlier stage of hypertension had significantly lower (-25 to-50%, P smaller than 0.01) arterial norepinephrine than either the sham or nonhypertensive animals. The water and cation content of arteries was unchanged, but aortic tissue contained significantly more water, sodium, potassium, and magnesium than the nonhypertensives. Hypertensives autopsied at 60 days also had lower arterial norepinephrine content than sham and nonhypertensive animals, but this refuction was not significant. Their arterial and aortic tissue contained more water and cations than the nonhypertensive, sham, unoperated, and unilaterally nephrectomized dogs. It is suggested that in the initial stage of renovascular hypertension the arterial norepinephrine content is reduced significantly, whereas at a later stage the arterial water and cations may be involved in the maintenance of an elevated blood pressure.", "contents": "Arterial water, cations, and norepinephrine in early and late renovascular hypertension. In dogs made hypertensive renal artery stenosis and contralateral nephrectomy, the arterial and myocardial tissue content of water, cations (sodium, potassium, magnesium, calcium), and norepinephrine was measured 20 and 60 days after the operation. Hypertensive animals autopsied at the earlier stage of hypertension had significantly lower (-25 to-50%, P smaller than 0.01) arterial norepinephrine than either the sham or nonhypertensive animals. The water and cation content of arteries was unchanged, but aortic tissue contained significantly more water, sodium, potassium, and magnesium than the nonhypertensives. Hypertensives autopsied at 60 days also had lower arterial norepinephrine content than sham and nonhypertensive animals, but this refuction was not significant. Their arterial and aortic tissue contained more water and cations than the nonhypertensive, sham, unoperated, and unilaterally nephrectomized dogs. It is suggested that in the initial stage of renovascular hypertension the arterial norepinephrine content is reduced significantly, whereas at a later stage the arterial water and cations may be involved in the maintenance of an elevated blood pressure."} {"id": "PMID:165732", "title": "Transport of Na, Cl, and water by the rabbit corneal epithelium at resting potential.", "content": "Theophylline (1 mM) produced a net transport of Na and Cl from aqueous humor to tears (.02-.04 mumol/cm2 h) in the isolated rabbit cornea denuded of endothlium and in the presence of normal resting potential (25-35 mV). The active transport of Na (tears to aqueous) and of Cl (aqueous to tears), estimated with the Goldman constant-field equations, was confirmed. A 10 degrees C rise in temperature produced changes close to those predicted for passive processes in both unidirectional fluxes of Na and in the tears-to-aqueous flux of Cl, but not for the aqueous-to-tears flux of Cl. Theophylline treatment doubled Cl permeability but did not significantly affect Na or urea permeability, suggestingspecificity of affect. In separate experiments it was shown that stromal thinning occurred in previously swollen corneas when the endothelium was blocked by silicone oil and the epithelium was treated with theophylline. These findings provide further support for the argument that the mammalian epithelium could have an active role in the regulation of corneal thickness in situ.", "contents": "Transport of Na, Cl, and water by the rabbit corneal epithelium at resting potential. Theophylline (1 mM) produced a net transport of Na and Cl from aqueous humor to tears (.02-.04 mumol/cm2 h) in the isolated rabbit cornea denuded of endothlium and in the presence of normal resting potential (25-35 mV). The active transport of Na (tears to aqueous) and of Cl (aqueous to tears), estimated with the Goldman constant-field equations, was confirmed. A 10 degrees C rise in temperature produced changes close to those predicted for passive processes in both unidirectional fluxes of Na and in the tears-to-aqueous flux of Cl, but not for the aqueous-to-tears flux of Cl. Theophylline treatment doubled Cl permeability but did not significantly affect Na or urea permeability, suggestingspecificity of affect. In separate experiments it was shown that stromal thinning occurred in previously swollen corneas when the endothelium was blocked by silicone oil and the epithelium was treated with theophylline. These findings provide further support for the argument that the mammalian epithelium could have an active role in the regulation of corneal thickness in situ."} {"id": "PMID:165733", "title": "Mechanism of cholecystokinin inhibition of lower esophageal sphincter pressure.", "content": "The purpose of this study were 1) to quantify the lower esophageal sphincter (LES) response to intravenous cholecystokinin (CCK) in both man and the opossum in vivo, 2) to characterize the interaction of CCK and gastrin on circular muscle of the LES, and 3) to determine the site of action of CCK on LES muscle. In both man and the opossum LES pressure was decreased significantly by either constant intravenous infusion or bolus injection of CCK. In vitro dose-response curves to gastrin I, CCK, and the octapeptide of CCK (OP) demonstrated that both CCK and OP were partial agonists on the LES muscle. Both CCK and OP contract LES muscle at lower threshold doses, but give smaller maximum responses than gastrin I. The maximum response of LES muscle to CCK was antagonized only by atropine and tetrodotoxin, but not by other antagonists, suggesting that CCK contracts LES muscle by acetylcholine release. In vitro studies on LES muscle showed that CCK selectively antagonized the effect of gastrin I, but not other agonists. These studied suggest that CCK reduces LES pressure in vivo by inhibition of the endogenous gastrin effect.", "contents": "Mechanism of cholecystokinin inhibition of lower esophageal sphincter pressure. The purpose of this study were 1) to quantify the lower esophageal sphincter (LES) response to intravenous cholecystokinin (CCK) in both man and the opossum in vivo, 2) to characterize the interaction of CCK and gastrin on circular muscle of the LES, and 3) to determine the site of action of CCK on LES muscle. In both man and the opossum LES pressure was decreased significantly by either constant intravenous infusion or bolus injection of CCK. In vitro dose-response curves to gastrin I, CCK, and the octapeptide of CCK (OP) demonstrated that both CCK and OP were partial agonists on the LES muscle. Both CCK and OP contract LES muscle at lower threshold doses, but give smaller maximum responses than gastrin I. The maximum response of LES muscle to CCK was antagonized only by atropine and tetrodotoxin, but not by other antagonists, suggesting that CCK contracts LES muscle by acetylcholine release. In vitro studies on LES muscle showed that CCK selectively antagonized the effect of gastrin I, but not other agonists. These studied suggest that CCK reduces LES pressure in vivo by inhibition of the endogenous gastrin effect."} {"id": "PMID:165734", "title": "Effect of amino acid meals on hepatic alpha-aminoisobutyrate transport and cyclic AMP.", "content": "Within 1.5 h after force-feeding rats one meal of enzymatic hydrolysates of casein, gelatin, lactalbumin, or yeast, alpha-aminoisobutyric acid (AIB) transport in liver slices was stimulated two- to threefold. A complete amino acid mixture also increased AIB transport. Of the 15 amino acids or derivatives tested individually, the dispensable amino acids, especially glycine and alanine, were more stimulatory than the essential amino acids; feeding a mixture of amino acids lacking glycine and alanine increased AIB uptake only slightly. The effects were significantly greater in meal-fed than in ad libitum-fed rats. Increased hepatic concentrations of cyclic AM were usually associated with the increase in AIB transport. Feeding glucose inhibited the increases in transport and cyclic AMP concentration induced by casein hydrolysate or in the stimulation of AIB transport by dietary amino acids. The increases in AIB uptake appeared unrelated to the exchange of endogenous amino acids with medium AIB.", "contents": "Effect of amino acid meals on hepatic alpha-aminoisobutyrate transport and cyclic AMP. Within 1.5 h after force-feeding rats one meal of enzymatic hydrolysates of casein, gelatin, lactalbumin, or yeast, alpha-aminoisobutyric acid (AIB) transport in liver slices was stimulated two- to threefold. A complete amino acid mixture also increased AIB transport. Of the 15 amino acids or derivatives tested individually, the dispensable amino acids, especially glycine and alanine, were more stimulatory than the essential amino acids; feeding a mixture of amino acids lacking glycine and alanine increased AIB uptake only slightly. The effects were significantly greater in meal-fed than in ad libitum-fed rats. Increased hepatic concentrations of cyclic AM were usually associated with the increase in AIB transport. Feeding glucose inhibited the increases in transport and cyclic AMP concentration induced by casein hydrolysate or in the stimulation of AIB transport by dietary amino acids. The increases in AIB uptake appeared unrelated to the exchange of endogenous amino acids with medium AIB."} {"id": "PMID:165735", "title": "Granular cell myoblastoma of the cystic duct. A case associated with hydrops of the gallbladder.", "content": "The first known case of true hydrops of the gallbladder that resulted from granular cell myoblastoma is reported. Granular cell tumors are benign multicentric tumors that should be treated by total excision so that free margins are assured. These tumors are rarely found in the biliary tract; however, they may cause complications of biliary tract obstruction.", "contents": "Granular cell myoblastoma of the cystic duct. A case associated with hydrops of the gallbladder. The first known case of true hydrops of the gallbladder that resulted from granular cell myoblastoma is reported. Granular cell tumors are benign multicentric tumors that should be treated by total excision so that free margins are assured. These tumors are rarely found in the biliary tract; however, they may cause complications of biliary tract obstruction."} {"id": "PMID:165736", "title": "Alopecia, ascites, and incomplete regeneration after 85 to 90 per cent liver resection.", "content": "A nineteen year old female underwent 85 to 90 per cent partial hepatectomy to treat a minimal deviation hepatoma. Observations afterwards suggested that the limit of resection compatible with survival had been reached. She recovered perfect health after many months, although liver regeneration was not complete. Severe but eventually reversible alopecia and ascites developed postoperatively, undoubtedly as a complication of the massive hepatic resection.", "contents": "Alopecia, ascites, and incomplete regeneration after 85 to 90 per cent liver resection. A nineteen year old female underwent 85 to 90 per cent partial hepatectomy to treat a minimal deviation hepatoma. Observations afterwards suggested that the limit of resection compatible with survival had been reached. She recovered perfect health after many months, although liver regeneration was not complete. Severe but eventually reversible alopecia and ascites developed postoperatively, undoubtedly as a complication of the massive hepatic resection."} {"id": "PMID:165737", "title": "Intraoperative physiologic monitoring and management during hepatic lobectomy using the liver isolation-perfusion technic.", "content": "The high operative mortality of major hepatic resection for tumor can be improved by a technic of resection using complete vascular isolation and hypothermic perfusion of the liver. Complete clamping of the portal vein, vena cava, and hepatic artery was necessary and well tolerated. Major physiologic, biochemical, and coagulation changes, however, can occur with this technic that requires close monitoring by the anesthesiologist. With astute observation and prompt corrective measures when indicated, these changes can be minimized to enable a safe and smooth resection to be carried out.", "contents": "Intraoperative physiologic monitoring and management during hepatic lobectomy using the liver isolation-perfusion technic. The high operative mortality of major hepatic resection for tumor can be improved by a technic of resection using complete vascular isolation and hypothermic perfusion of the liver. Complete clamping of the portal vein, vena cava, and hepatic artery was necessary and well tolerated. Major physiologic, biochemical, and coagulation changes, however, can occur with this technic that requires close monitoring by the anesthesiologist. With astute observation and prompt corrective measures when indicated, these changes can be minimized to enable a safe and smooth resection to be carried out."} {"id": "PMID:165738", "title": "Thyrolymphography.", "content": "The present investigation shows that the capacity of thyrolymphography for demonstrating the morphologic features of various thyroid lesions is not inferior to that of isotope scanning. On the contrary, lymphography is an effective procedure for detecting small nodules that remain undetected by other methods. Contrast medium is more rapidly distributed to lymph nodes in patients with diffuse goiter and also in patients pretreated with Lugol's solution. Finally, it is shown that the contrast medium employed (Lipiodol Ultra Fluid) remains in the lymph nodes for a period of several months.", "contents": "Thyrolymphography. The present investigation shows that the capacity of thyrolymphography for demonstrating the morphologic features of various thyroid lesions is not inferior to that of isotope scanning. On the contrary, lymphography is an effective procedure for detecting small nodules that remain undetected by other methods. Contrast medium is more rapidly distributed to lymph nodes in patients with diffuse goiter and also in patients pretreated with Lugol's solution. Finally, it is shown that the contrast medium employed (Lipiodol Ultra Fluid) remains in the lymph nodes for a period of several months."} {"id": "PMID:165739", "title": "Total pancreatectomy with primary mesenteric vascular reconstruction.", "content": "Total pancreaticoduodenectomy with resection of the superior mesenteric artery and vein was performed in a sixty-two year old man with islet cell carcinoma of the pancreas. Arterial reconstruction was accomplished with an aortomesenteric interposition Dacron graft. The venous system was reanastomosed primarily, the infrapancreatic superior mesenteric vein to the portal vein in the hepatic hilum. This procedure, although it did not result in long-term survival, demonstrates the technical feasibility of wide regional resection for tumors of the pancreas impinging upon the mesenteric vasculature in the region of the neck and uncinate process.", "contents": "Total pancreatectomy with primary mesenteric vascular reconstruction. Total pancreaticoduodenectomy with resection of the superior mesenteric artery and vein was performed in a sixty-two year old man with islet cell carcinoma of the pancreas. Arterial reconstruction was accomplished with an aortomesenteric interposition Dacron graft. The venous system was reanastomosed primarily, the infrapancreatic superior mesenteric vein to the portal vein in the hepatic hilum. This procedure, although it did not result in long-term survival, demonstrates the technical feasibility of wide regional resection for tumors of the pancreas impinging upon the mesenteric vasculature in the region of the neck and uncinate process."} {"id": "PMID:165740", "title": "Parotid gland tumors. Clinicopathologic study.", "content": "The clinical findings and histologic features of 154 parotid gland tumors treated at the Health Sciences Centre, Winnipeg, Canada, from 1957 to 1970 were reviewed. The study illustrates a wide variation in the natural history and degree of malignancy of parotid tumors. Approximately 80 per cent were benign; among these, mixed tumors were by far the commonest. For most benign tumors, the recommended surgical treatment is wide local excision with an adequate margin of normal glandular tissue, except when subtotal or conservative total parotidectomy is required because of the size or location of the tumor. The facial nerve should be visualized and preserved. This approach prevents recurrences and minimizes facial nerve injury, since risk of neural injury increases with the extent of the surgical procedure. Total removal of the gland on the basis of the multicentricity or malignant transformation of these tumors is not supported by the findings of this study. For malignant tumors a more radical procedure, that is, subtotal or total parotidectomy with or without node dissection, with sacrifice of the facial nerve if necessary is advisable, depending on the type and anatomic location of the tumor.", "contents": "Parotid gland tumors. Clinicopathologic study. The clinical findings and histologic features of 154 parotid gland tumors treated at the Health Sciences Centre, Winnipeg, Canada, from 1957 to 1970 were reviewed. The study illustrates a wide variation in the natural history and degree of malignancy of parotid tumors. Approximately 80 per cent were benign; among these, mixed tumors were by far the commonest. For most benign tumors, the recommended surgical treatment is wide local excision with an adequate margin of normal glandular tissue, except when subtotal or conservative total parotidectomy is required because of the size or location of the tumor. The facial nerve should be visualized and preserved. This approach prevents recurrences and minimizes facial nerve injury, since risk of neural injury increases with the extent of the surgical procedure. Total removal of the gland on the basis of the multicentricity or malignant transformation of these tumors is not supported by the findings of this study. For malignant tumors a more radical procedure, that is, subtotal or total parotidectomy with or without node dissection, with sacrifice of the facial nerve if necessary is advisable, depending on the type and anatomic location of the tumor."} {"id": "PMID:165741", "title": "Electron microscopic studies on zonular fibers. II. Changes of the zonular fibers after the treatment with collagenase, alpha-chymotrypsin and hyaluronidase.", "content": "Adult rabbit zonular fibers maintained in their native condition were treated with collagenase, alpha-chymotrypsin and hyaluronidase, and were observed with the electron microscope. The results obtained were as follows: 1. Collagenase digested the lens capsule, but not the zonular fibers. 2. Long time collagenase action obscured the cell membrane of the lens epithelium and the basal lamina of the ciliary epithelium. 3. Washing with 0.9% NaCl increased the collagenase action on the lens capsule. 4. Alpha-chymotrypsin digested the zonular fibers and the zonular lemalla, but not the lens capsule and the basal lamina of the ciliary epithelium. 5, Hyaluronidase only slightly changed the lens capsule. 6. The vitreous fibers were digested by collagenase, but not by alpha-chymotrypsin or hyaluronidase. Thes results together with the review of recent literature indicate that the zonular fiber has a nature close to that of the microfibril of elastic fiber.", "contents": "Electron microscopic studies on zonular fibers. II. Changes of the zonular fibers after the treatment with collagenase, alpha-chymotrypsin and hyaluronidase. Adult rabbit zonular fibers maintained in their native condition were treated with collagenase, alpha-chymotrypsin and hyaluronidase, and were observed with the electron microscope. The results obtained were as follows: 1. Collagenase digested the lens capsule, but not the zonular fibers. 2. Long time collagenase action obscured the cell membrane of the lens epithelium and the basal lamina of the ciliary epithelium. 3. Washing with 0.9% NaCl increased the collagenase action on the lens capsule. 4. Alpha-chymotrypsin digested the zonular fibers and the zonular lemalla, but not the lens capsule and the basal lamina of the ciliary epithelium. 5, Hyaluronidase only slightly changed the lens capsule. 6. The vitreous fibers were digested by collagenase, but not by alpha-chymotrypsin or hyaluronidase. Thes results together with the review of recent literature indicate that the zonular fiber has a nature close to that of the microfibril of elastic fiber."} {"id": "PMID:165742", "title": "The influence of diazepam on the dosage of muscel-relaxants during anaesthesia.", "content": "The literature on anaesthesiological studies performed to investigate a possible sparing effect of diazepam on the dosage of muscle-relaxants during anaesthesia is reviewed. Despite some conflicting results it can be concluded that diazepam exerts such an effect, thus allowing between 8 and 30% of the amounts of muscle-relaxants, depending on the type of anesthesia used, to be spared. This conclusion is also supported by the results of pharmacological studies in animals, using the head drop method. The mechanism of this effect is discussed on the basis of the relevant published pharmacological evidence from \"in vitro\" studies and from both animal and human \"in vivo\" studies. From these reports it is concluded that diazepam, at therapeutic doses, does not act on neuromuscular transmission and that this sparing effect does not result from direct pharmacological interaction with neuromuscular blocking agents. Some studies indicate a minimal action of the product on the skeletal muscle fibre, but this also is not related to the sparing effect. It is furthermore concluded that his sparing effect of diazepam on the dosage of muscle-relaxants during anesthesia is due to a summation of muscle-relaxant actions exerted at different levels of the nervous system, those of diazepam being mainly exerted at the spinal and brainstem level and consisting in inhibition of polysynaptic reflex activity, enhancement of presynaptic inhibition, and depression of gamma-motoneuron activity.", "contents": "The influence of diazepam on the dosage of muscel-relaxants during anaesthesia. The literature on anaesthesiological studies performed to investigate a possible sparing effect of diazepam on the dosage of muscle-relaxants during anaesthesia is reviewed. Despite some conflicting results it can be concluded that diazepam exerts such an effect, thus allowing between 8 and 30% of the amounts of muscle-relaxants, depending on the type of anesthesia used, to be spared. This conclusion is also supported by the results of pharmacological studies in animals, using the head drop method. The mechanism of this effect is discussed on the basis of the relevant published pharmacological evidence from \"in vitro\" studies and from both animal and human \"in vivo\" studies. From these reports it is concluded that diazepam, at therapeutic doses, does not act on neuromuscular transmission and that this sparing effect does not result from direct pharmacological interaction with neuromuscular blocking agents. Some studies indicate a minimal action of the product on the skeletal muscle fibre, but this also is not related to the sparing effect. It is furthermore concluded that his sparing effect of diazepam on the dosage of muscle-relaxants during anesthesia is due to a summation of muscle-relaxant actions exerted at different levels of the nervous system, those of diazepam being mainly exerted at the spinal and brainstem level and consisting in inhibition of polysynaptic reflex activity, enhancement of presynaptic inhibition, and depression of gamma-motoneuron activity."} {"id": "PMID:165756", "title": "Actions of a new muscle relaxant (AH8165) on neuromuscular transmission.", "content": "The effects of a new muscle relaxant, AH8165, on miniature endplate potential (MEPP) amplitude and frequency, endplate sensitivity to acetylcholine, and muscle twitch tension were studied in vitro in the frog sartorius muscle. Nerve terminal effects were studied in vivo in the cat soleus muscle and its ventral root fibers. AH8165 stimulates the nerve terminal, as evidenced by increased MEPP frequency and the appearance of post-drug repetitive activity. In the same concentration range at which MEPP frequency is increased, MEPP amplitude, endplate sensitivity to acetylcholine, and twitch tension are decreased. This suggests that AH8165 produces muscle relaxation by blocking postsynaptic cholinergic receptors. (Key works: Neuromuscular relaxants, AH8165.).", "contents": "Actions of a new muscle relaxant (AH8165) on neuromuscular transmission. The effects of a new muscle relaxant, AH8165, on miniature endplate potential (MEPP) amplitude and frequency, endplate sensitivity to acetylcholine, and muscle twitch tension were studied in vitro in the frog sartorius muscle. Nerve terminal effects were studied in vivo in the cat soleus muscle and its ventral root fibers. AH8165 stimulates the nerve terminal, as evidenced by increased MEPP frequency and the appearance of post-drug repetitive activity. In the same concentration range at which MEPP frequency is increased, MEPP amplitude, endplate sensitivity to acetylcholine, and twitch tension are decreased. This suggests that AH8165 produces muscle relaxation by blocking postsynaptic cholinergic receptors. (Key works: Neuromuscular relaxants, AH8165.)."} {"id": "PMID:165758", "title": "Use of a rapid brain-sampling technique in a physiologic preparation: effects of morphine, ketamine, and halothane on tissue energy intermediates.", "content": "A new method of rapid sampling of brain tissue, \"freeze-blowing,\" has been used to compare the neurochemistry of the brain during anesthesia with that in the awake state. The method avoids anoxia associated with the sampling process. Physiologic variables, including body temperature, blood-gas tensions and blood pressure, were carefully monitored and controlled in the experimental animals. None of the agents tested (halothane, morphine, and ketamine) reduced the brain tissue high-energy phosphate reserved. All three drugs doubled glucose levels. Morphine lowered both lactate and the lactate/pyruvate ratio. Uniformly, the three anesthetic agents led to twofold increases of brain cyclic 3'-5' adenosine monophosphate concentrations. These changes suggest a possible role for cyclic nucleotides in central neurotransmission.", "contents": "Use of a rapid brain-sampling technique in a physiologic preparation: effects of morphine, ketamine, and halothane on tissue energy intermediates. A new method of rapid sampling of brain tissue, \"freeze-blowing,\" has been used to compare the neurochemistry of the brain during anesthesia with that in the awake state. The method avoids anoxia associated with the sampling process. Physiologic variables, including body temperature, blood-gas tensions and blood pressure, were carefully monitored and controlled in the experimental animals. None of the agents tested (halothane, morphine, and ketamine) reduced the brain tissue high-energy phosphate reserved. All three drugs doubled glucose levels. Morphine lowered both lactate and the lactate/pyruvate ratio. Uniformly, the three anesthetic agents led to twofold increases of brain cyclic 3'-5' adenosine monophosphate concentrations. These changes suggest a possible role for cyclic nucleotides in central neurotransmission."} {"id": "PMID:165762", "title": "The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in Aplysia ganglion cells.", "content": "The effects of DMSO on single nerve cells of Aplysia were investigated by various electrophysiological methods. 1. Although the increase in permeability of the biological membranes produced by DMSO has been well documented, we found that DMSO at concentration of less than 20% actually decreases the permeability of the neuronal membranes, probably toward potassium and chloride ions. This change in ionic permeability reversibly depolarizes the resting membranes and makes the neurons more excitable. 2. The falling phase of the spike is prolonged by 8% DMSO, because it blocks the active increase in potassium permeability. This change suppresses the high frequency discharge, because the refractory period of each spike is increased. Neither the rising phase nor the absolute firing level is appreciably altered by DMSO when these are examined after the depolarization is cancelled. 3. Dilute DMSO (less than 1%) facilitates cholinergic trasmission because it blocks ACh-esterase activity. DMSO at concentrations of more than 10% ultimately blocks cholinergic transmission entirely, because it also depresses cholinoceptive receptor activity (probably by allosteric interaction). The action of 1-10% DMSO is complicated, because both facilitatory and inhibitory effects take place at the same time. 4. In cholinergic synapses, excitatory transmission is more susceptible to DMSO than inhibitory transmission. This is because the activity of the excitatory receptor is blocked more readily than that of the inhibitory receptor. The depressing effects of DMSO are not specific to the cholinergic system, however, since the activities of GABA and glutamate receptors are similarly depressed.", "contents": "The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in Aplysia ganglion cells. The effects of DMSO on single nerve cells of Aplysia were investigated by various electrophysiological methods. 1. Although the increase in permeability of the biological membranes produced by DMSO has been well documented, we found that DMSO at concentration of less than 20% actually decreases the permeability of the neuronal membranes, probably toward potassium and chloride ions. This change in ionic permeability reversibly depolarizes the resting membranes and makes the neurons more excitable. 2. The falling phase of the spike is prolonged by 8% DMSO, because it blocks the active increase in potassium permeability. This change suppresses the high frequency discharge, because the refractory period of each spike is increased. Neither the rising phase nor the absolute firing level is appreciably altered by DMSO when these are examined after the depolarization is cancelled. 3. Dilute DMSO (less than 1%) facilitates cholinergic trasmission because it blocks ACh-esterase activity. DMSO at concentrations of more than 10% ultimately blocks cholinergic transmission entirely, because it also depresses cholinoceptive receptor activity (probably by allosteric interaction). The action of 1-10% DMSO is complicated, because both facilitatory and inhibitory effects take place at the same time. 4. In cholinergic synapses, excitatory transmission is more susceptible to DMSO than inhibitory transmission. This is because the activity of the excitatory receptor is blocked more readily than that of the inhibitory receptor. The depressing effects of DMSO are not specific to the cholinergic system, however, since the activities of GABA and glutamate receptors are similarly depressed."} {"id": "PMID:165763", "title": "Specific modifications of the Na+,K+-dependent adenosine triphosphatase by dimethyl sulfoxide.", "content": "DMSO inhibits the Na+, K+-ATPase, but stimulates the associated K+-phosphatase activity. For the ATPase, DMSO acts as an uncompetitive inhibitor toward both ATP and Na+, whereas it increases the K0.5 for K+. From measurements of the dissociation constant (Km) of these ions in the ligand states that correspond to the ATPase reaction, it can be shown that DMSO has little effect on the affinity for Na+, but decreases the affinity for K+ of the enzyme-phosphate intermediate (the form that has the highest affinity for K+). By contrast, DMSO decreases the Km for the phosphatase substrate (nitrophenyl phosphate) without affecting the Vmax. Moreover, DMSO decreases the K0.5 for K+ and also the Kd for K+ in the ligand states that correspond to the phosphatase reaction (which have only a moderate affinity for K+, since the acyl phosphate intermediate is absent in this pathway). These data may be incorporated into a reaction mechanism for the Na+, K+-ATPase. Initially the enzyme is phosphorylated to form an acyl phosphate intermediate, in steps that require Na+ and Mg-2+. At this stage the affinity of K+ is markedly increased (from the moderate affinity seen in the \"free\" enzyme and the phosphatase reaction). When K+ is bound, the phosphate group is transferred to the hydrolytic site where P-i is ultimately released. DMSO acts at the point at which the acyl phosphate group or the phosphatase substrate enters the hydrolytic site, inhibiting one and facilitating the other. At this stage the affinity for K+ is also changing, and DMSO apparently selects an enyme conformation of intermediate affinity. Ion transport may occur by a gate mechanism in an overall system that operates on a half-of-the-sites active enzyme pattern in which ATP hydrolysis may alternate between the dimeric subunits of the enzyme.", "contents": "Specific modifications of the Na+,K+-dependent adenosine triphosphatase by dimethyl sulfoxide. DMSO inhibits the Na+, K+-ATPase, but stimulates the associated K+-phosphatase activity. For the ATPase, DMSO acts as an uncompetitive inhibitor toward both ATP and Na+, whereas it increases the K0.5 for K+. From measurements of the dissociation constant (Km) of these ions in the ligand states that correspond to the ATPase reaction, it can be shown that DMSO has little effect on the affinity for Na+, but decreases the affinity for K+ of the enzyme-phosphate intermediate (the form that has the highest affinity for K+). By contrast, DMSO decreases the Km for the phosphatase substrate (nitrophenyl phosphate) without affecting the Vmax. Moreover, DMSO decreases the K0.5 for K+ and also the Kd for K+ in the ligand states that correspond to the phosphatase reaction (which have only a moderate affinity for K+, since the acyl phosphate intermediate is absent in this pathway). These data may be incorporated into a reaction mechanism for the Na+, K+-ATPase. Initially the enzyme is phosphorylated to form an acyl phosphate intermediate, in steps that require Na+ and Mg-2+. At this stage the affinity of K+ is markedly increased (from the moderate affinity seen in the \"free\" enzyme and the phosphatase reaction). When K+ is bound, the phosphate group is transferred to the hydrolytic site where P-i is ultimately released. DMSO acts at the point at which the acyl phosphate group or the phosphatase substrate enters the hydrolytic site, inhibiting one and facilitating the other. At this stage the affinity for K+ is also changing, and DMSO apparently selects an enyme conformation of intermediate affinity. Ion transport may occur by a gate mechanism in an overall system that operates on a half-of-the-sites active enzyme pattern in which ATP hydrolysis may alternate between the dimeric subunits of the enzyme."} {"id": "PMID:165764", "title": "Thymosin-induced differentiation of murine thymocytes in allogeneic mixed lymphocyte cultures.", "content": "Calf thymosin is shown to enhance the one-way MLR of CBA thymocytes cultured with allogeneic mitomycin-C- treated C57BL/J6 spleen cells. Thymosin does not enhance the one-way MLR of CBA thymocytes cultured with syngeneic mitomucin-C-treated spleen cells. Based on this finding we present a relatively simple, rapid and quantitative in vitro microculture hioassay for inducers of T-cell differentiation and propose that thymosin treatment, when accompanied by antigen presentation, induces the two-step maturational sequence of pre-T yields T1 yields T2.", "contents": "Thymosin-induced differentiation of murine thymocytes in allogeneic mixed lymphocyte cultures. Calf thymosin is shown to enhance the one-way MLR of CBA thymocytes cultured with allogeneic mitomycin-C- treated C57BL/J6 spleen cells. Thymosin does not enhance the one-way MLR of CBA thymocytes cultured with syngeneic mitomucin-C-treated spleen cells. Based on this finding we present a relatively simple, rapid and quantitative in vitro microculture hioassay for inducers of T-cell differentiation and propose that thymosin treatment, when accompanied by antigen presentation, induces the two-step maturational sequence of pre-T yields T1 yields T2."} {"id": "PMID:165765", "title": "The isolation of thymopoietin (thymin).", "content": "The isolation from bovine thymus of two closely related polypeptides, thymopoietin I and II, is described. These are considered to be thymic hormones, which physiologically induce the differentation of prothymocytes to thymocytes within the thymus. Ths isolation of the thymopoietins was monitored not by their differentiative effects, but by a presumably secondary effect on neuromuscular transmission. This was discerned in experimental studies related to the human disease myasthenia gravis in which it was suggested that autoimmune thymitis was regularly present. In an animal model, experimental autoimmune thymitis, the thymic disease was shown to result in the release of a substance that depressed neuromuscular transmission and this substance was shown to be also secreted in small amounts by the normal thymus. A bioassay was developed, this being the delayed appearance of neuromuscular impairment after in vivo injection of the active material, and this bioassay was used to monitor the fractionation of thymus extracts and isolate thymopoietin. Pure thymopoietin was active at subnanogram concentrations, both in producing its effect on neuromuscualr transmission and in inducing the differentiation of prothymocytes to thymocytes. This potency of activity of the purified polypeptide, as well as its specificity in inducing the differentiation of T-cells and not B-cells, support the consideration that thympoietin is a physiological inducing hormone produced by the thymus. This is further supported by the evidence that thymopoietin is only produced in the thymus: neuromuscular blocking effects are not present in extracts of other tissues and immunofluorescent localization of thymopoietin shows it to be present only in thymic epithelial cells.", "contents": "The isolation of thymopoietin (thymin). The isolation from bovine thymus of two closely related polypeptides, thymopoietin I and II, is described. These are considered to be thymic hormones, which physiologically induce the differentation of prothymocytes to thymocytes within the thymus. Ths isolation of the thymopoietins was monitored not by their differentiative effects, but by a presumably secondary effect on neuromuscular transmission. This was discerned in experimental studies related to the human disease myasthenia gravis in which it was suggested that autoimmune thymitis was regularly present. In an animal model, experimental autoimmune thymitis, the thymic disease was shown to result in the release of a substance that depressed neuromuscular transmission and this substance was shown to be also secreted in small amounts by the normal thymus. A bioassay was developed, this being the delayed appearance of neuromuscular impairment after in vivo injection of the active material, and this bioassay was used to monitor the fractionation of thymus extracts and isolate thymopoietin. Pure thymopoietin was active at subnanogram concentrations, both in producing its effect on neuromuscualr transmission and in inducing the differentiation of prothymocytes to thymocytes. This potency of activity of the purified polypeptide, as well as its specificity in inducing the differentiation of T-cells and not B-cells, support the consideration that thympoietin is a physiological inducing hormone produced by the thymus. This is further supported by the evidence that thymopoietin is only produced in the thymus: neuromuscular blocking effects are not present in extracts of other tissues and immunofluorescent localization of thymopoietin shows it to be present only in thymic epithelial cells."} {"id": "PMID:165766", "title": "Regulation of theta-antigen expression by agents altering cyclic AMP level and by thymic factor.", "content": "Thymic factor, cyclic AMP, and products increasing its cellular level, such as Prostaglandin E1, induce the appearance of the theta-antigen on T-cell precursors whether assessed by a rossette-inhibition assay or a cytotoxic assay after cell fractionation on BSA discontinuous gradiet. Synergism has been demonstrated between cyclic AMPT and TF for that effect. Conversely, decrease of theta expression has been obtained by altering cyclic AMP level in theta-positive cells either increasing it by dibutyryl cAMP treatment or decreasing it by indomethacin treatment. Finally, these data suggest the involvement of cyclic AMP in the regulation of theta expression under thymic hormone control.", "contents": "Regulation of theta-antigen expression by agents altering cyclic AMP level and by thymic factor. Thymic factor, cyclic AMP, and products increasing its cellular level, such as Prostaglandin E1, induce the appearance of the theta-antigen on T-cell precursors whether assessed by a rossette-inhibition assay or a cytotoxic assay after cell fractionation on BSA discontinuous gradiet. Synergism has been demonstrated between cyclic AMPT and TF for that effect. Conversely, decrease of theta expression has been obtained by altering cyclic AMP level in theta-positive cells either increasing it by dibutyryl cAMP treatment or decreasing it by indomethacin treatment. Finally, these data suggest the involvement of cyclic AMP in the regulation of theta expression under thymic hormone control."} {"id": "PMID:165768", "title": "Influence of the thymus-corticothropin-growth hormone interaction on the rejection of skin allografts in the rat.", "content": "Skin allograft rejection was noticeably delayed in rats following hypophysectomy. Daily injections of hypophyseal growth hormone restored the normal reaction. Additional thymectomy had no influence on the rejection of hypophysectomized rats. In these animals growth hormone by itself had no significant influence on the graft rejection. It only restored a normal reaction when given together with thymic hormone. Corticotropin injections accelerated the allograft rejection. On this action of corticotropin thymic hormone has shown a significant inhibitory influence. The thymus was thus proved to be a synergist to growth hormone and an antagonist to corticotropin. Previous observations made with usual endocrinological test- are thus confirmed with an immunological test.", "contents": "Influence of the thymus-corticothropin-growth hormone interaction on the rejection of skin allografts in the rat. Skin allograft rejection was noticeably delayed in rats following hypophysectomy. Daily injections of hypophyseal growth hormone restored the normal reaction. Additional thymectomy had no influence on the rejection of hypophysectomized rats. In these animals growth hormone by itself had no significant influence on the graft rejection. It only restored a normal reaction when given together with thymic hormone. Corticotropin injections accelerated the allograft rejection. On this action of corticotropin thymic hormone has shown a significant inhibitory influence. The thymus was thus proved to be a synergist to growth hormone and an antagonist to corticotropin. Previous observations made with usual endocrinological test- are thus confirmed with an immunological test."} {"id": "PMID:165769", "title": "Stimulation of cAMP levels and modulation of antibody formation in mice immunized with cholera toxin.", "content": "Injection of mice with 1.0 mu g of a purified exotoxin derived from Vitro cholerae together with a challenge injection of sheep erythrocytes (SRBC)P OR E. coli LPS markedly influenced the immune response to these antigens. Simultaneous injection of the toxin with antigen resulted in a delayed appearance of antibody-forming cells during the first few days after immunization, followed by a marked enhancement of the peak numbers of antibody-forming cells. In the case of the immune response to SRBC, both 19S and 7S plaque-forming cells (PFC) were enhanced on the peak day of response after simulataneous immunization of toxin-injected mice. The secondary immune response to SRBC was also similarly affected when cholera toxin was given along with a second injection of erythrocytes: i.e. a delay in appearance of the first antibody-forming cells followed by a marked enhancement of the peak 19S and 7S PFC response. Injection of cholera toxin 103 days prior to SRBC or LPS was immunosuppressive. The effect of cholera toxin on the level of splenic cyclic AMP appeared related to the effects on antibody formation.", "contents": "Stimulation of cAMP levels and modulation of antibody formation in mice immunized with cholera toxin. Injection of mice with 1.0 mu g of a purified exotoxin derived from Vitro cholerae together with a challenge injection of sheep erythrocytes (SRBC)P OR E. coli LPS markedly influenced the immune response to these antigens. Simultaneous injection of the toxin with antigen resulted in a delayed appearance of antibody-forming cells during the first few days after immunization, followed by a marked enhancement of the peak numbers of antibody-forming cells. In the case of the immune response to SRBC, both 19S and 7S plaque-forming cells (PFC) were enhanced on the peak day of response after simulataneous immunization of toxin-injected mice. The secondary immune response to SRBC was also similarly affected when cholera toxin was given along with a second injection of erythrocytes: i.e. a delay in appearance of the first antibody-forming cells followed by a marked enhancement of the peak 19S and 7S PFC response. Injection of cholera toxin 103 days prior to SRBC or LPS was immunosuppressive. The effect of cholera toxin on the level of splenic cyclic AMP appeared related to the effects on antibody formation."} {"id": "PMID:165771", "title": "The latero-medial inferior pontine syndrome.", "content": "A case is presented with a pontine vascular lesion involving the V, VI, VII, and VIII cranial nerves. The diagnostic evaluation included audiometry and electronystagmography as well as arteriography, pneumoencephalography, and brain scan. Total deafness developed in the involved ear and was present for seven weeks before complete recovery occurred. Electronystagmographic findings consistent with a brain stem lesion also resolved following recovery of the patient. Audiometry and electronystagmography are described and documented for the first time in a report of a patient with a latero-medial inferior pontine syndrome. A discussion of some of the unique features of the brain stem vasculature and its relationship to clinical syndromes involving the brain stem is given.", "contents": "The latero-medial inferior pontine syndrome. A case is presented with a pontine vascular lesion involving the V, VI, VII, and VIII cranial nerves. The diagnostic evaluation included audiometry and electronystagmography as well as arteriography, pneumoencephalography, and brain scan. Total deafness developed in the involved ear and was present for seven weeks before complete recovery occurred. Electronystagmographic findings consistent with a brain stem lesion also resolved following recovery of the patient. Audiometry and electronystagmography are described and documented for the first time in a report of a patient with a latero-medial inferior pontine syndrome. A discussion of some of the unique features of the brain stem vasculature and its relationship to clinical syndromes involving the brain stem is given."} {"id": "PMID:165772", "title": "Value of special auditory tests in the latero-medial inferior pontine syndrome.", "content": "Results from a special battery of auditory tests are used to document, for the first time, recovery from a total unilateral hearing loss occurring as part of a latero-medial inferior pontine syndrome. Although sensitivity for pure tones and speech was regained within two months of onset, definite retrocochlear signs persisted for nine months. The tests which best demonstrated the lingering retrocochlear abnormality were binaural masking level difference procedures for 500 Hz pure tones and speech and examination of the amplitude of the acoustic reflex over a ten second time period. The relative sensitivity of other speech and pure tone tasks in detecting the retrocochlear problem is detailed.", "contents": "Value of special auditory tests in the latero-medial inferior pontine syndrome. Results from a special battery of auditory tests are used to document, for the first time, recovery from a total unilateral hearing loss occurring as part of a latero-medial inferior pontine syndrome. Although sensitivity for pure tones and speech was regained within two months of onset, definite retrocochlear signs persisted for nine months. The tests which best demonstrated the lingering retrocochlear abnormality were binaural masking level difference procedures for 500 Hz pure tones and speech and examination of the amplitude of the acoustic reflex over a ten second time period. The relative sensitivity of other speech and pure tone tasks in detecting the retrocochlear problem is detailed."} {"id": "PMID:165782", "title": "Basal cell carcinomas and basal cell carcinoma-like changes overlying dermatofibromas.", "content": "Three patients had pigmented nodular basal cell carcinomas overlying dermatofibromas and 19 patients had basal cell carcinoma-like changes. We agree with the view generally held that acanthosis, pseudoepitheliomatous hyperplasia, basal cell buddings, and hair follicle-like proliferations of basal cells represent reactive changes of a spectrum of epidermal alterations overlying dermatofibromas. Contrary to the general opinion, however, we believe that basal cell carcinoma-like changes, superficial multicentric basal cell carcinomas, and nodular basal cell carcinomas represent neoplastic changes of such a spectrum.", "contents": "Basal cell carcinomas and basal cell carcinoma-like changes overlying dermatofibromas. Three patients had pigmented nodular basal cell carcinomas overlying dermatofibromas and 19 patients had basal cell carcinoma-like changes. We agree with the view generally held that acanthosis, pseudoepitheliomatous hyperplasia, basal cell buddings, and hair follicle-like proliferations of basal cells represent reactive changes of a spectrum of epidermal alterations overlying dermatofibromas. Contrary to the general opinion, however, we believe that basal cell carcinoma-like changes, superficial multicentric basal cell carcinomas, and nodular basal cell carcinomas represent neoplastic changes of such a spectrum."} {"id": "PMID:165783", "title": "A syndrome of trichoepitheliomas, milia, and cylindromas.", "content": "Three consecutive generations of a family have had members affected with trichoepitheliomas and milia. One member, the proband, also had cylindromas. The pattern of inheritance was a dominant one, with only the male members affected. Histopathologically, the trichoepitheliomas and milia contained keratinizing cysts with laminated centers, peripheral basaloid cells, and a thin granular layer. Fibroblastic stroma and fronding of basaloid cells were also seen in both tumors. The trichoepitheliomas and milia differed mainly in the greater proportion of keratinized cells found in the milia. Clinically, the milia were found only in areas of vellus hairs.", "contents": "A syndrome of trichoepitheliomas, milia, and cylindromas. Three consecutive generations of a family have had members affected with trichoepitheliomas and milia. One member, the proband, also had cylindromas. The pattern of inheritance was a dominant one, with only the male members affected. Histopathologically, the trichoepitheliomas and milia contained keratinizing cysts with laminated centers, peripheral basaloid cells, and a thin granular layer. Fibroblastic stroma and fronding of basaloid cells were also seen in both tumors. The trichoepitheliomas and milia differed mainly in the greater proportion of keratinized cells found in the milia. Clinically, the milia were found only in areas of vellus hairs."} {"id": "PMID:165784", "title": "EB-virus-specific IgM and IgG antibodies in first-degree relatives of children with acute lymphoblastic leukaemia.", "content": "EB-virus-specific IgM and IgG antibodies (to virus capsid and soluble complement fixing antigens) were estimated in sera from mothers and sibs of children with acute lymphoblastic leukaemia, from patients with infectious mononucleosis, and from control induviduals. IgM antibodies were present in 12 of 16 mothers and 3 of 4 sibs of children with acute lymphoblastic leukaemia. They were also present in 14 of 16 patients with infectious mononucleosis, but in only 1 of 12 control individuals.", "contents": "EB-virus-specific IgM and IgG antibodies in first-degree relatives of children with acute lymphoblastic leukaemia. EB-virus-specific IgM and IgG antibodies (to virus capsid and soluble complement fixing antigens) were estimated in sera from mothers and sibs of children with acute lymphoblastic leukaemia, from patients with infectious mononucleosis, and from control induviduals. IgM antibodies were present in 12 of 16 mothers and 3 of 4 sibs of children with acute lymphoblastic leukaemia. They were also present in 14 of 16 patients with infectious mononucleosis, but in only 1 of 12 control individuals."} {"id": "PMID:165785", "title": "Sexual precocity associated with a hypothalamic tumour. Effects of sex hormone therapy.", "content": "A case of sexual precocity of unusually early onset and associated with a hypothalamic tumour is described. The effects of ethinyl oestradiol and medroxyprogesterone acetate treatment have been monitored by plasma testosterone, FSH, and LH estimations. The results suggested a partial suppression of the tumour's influence, the mechanism of which is discussed.", "contents": "Sexual precocity associated with a hypothalamic tumour. Effects of sex hormone therapy. A case of sexual precocity of unusually early onset and associated with a hypothalamic tumour is described. The effects of ethinyl oestradiol and medroxyprogesterone acetate treatment have been monitored by plasma testosterone, FSH, and LH estimations. The results suggested a partial suppression of the tumour's influence, the mechanism of which is discussed."} {"id": "PMID:165786", "title": "Bone changes in congenital cytomegalic inclusion disease.", "content": "We report the case of a female infant born with cytomegalic inclusion disease, in whom bone changes were present in x-rays of the tibiae and femora. She was the mother's first child and was born 8 days postmature after a normal delivery; birthweight 2.52 kg. Many infarcts were seen in the placenta. The mother had a feverish illness at the 7th month of gestation, diagnosed by family doctor as influenza. No drugs had been given.", "contents": "Bone changes in congenital cytomegalic inclusion disease. We report the case of a female infant born with cytomegalic inclusion disease, in whom bone changes were present in x-rays of the tibiae and femora. She was the mother's first child and was born 8 days postmature after a normal delivery; birthweight 2.52 kg. Many infarcts were seen in the placenta. The mother had a feverish illness at the 7th month of gestation, diagnosed by family doctor as influenza. No drugs had been given."} {"id": "PMID:165787", "title": "Separation of human epidermal cells from fibroblasts in primary skin culture.", "content": "To obtain pure culture of epidermal cells from small human biopsies, two different techniques were tested and compared, i.e. separation of epidermis from corium before cultivation by trypsin and suction, and after cultivation by trypsin and collagenase. The most active growth of epidermal cells was obtained by the third technique, since short-term trypsin treatment released only fibroblasts from the culture. Crude collagenase (type I) was less effective than trypsin. Collagenase type II, III and IV had no effect on fibroblast release. Neither trypsin nor collagenases dispersed epidermal cells.", "contents": "Separation of human epidermal cells from fibroblasts in primary skin culture. To obtain pure culture of epidermal cells from small human biopsies, two different techniques were tested and compared, i.e. separation of epidermis from corium before cultivation by trypsin and suction, and after cultivation by trypsin and collagenase. The most active growth of epidermal cells was obtained by the third technique, since short-term trypsin treatment released only fibroblasts from the culture. Crude collagenase (type I) was less effective than trypsin. Collagenase type II, III and IV had no effect on fibroblast release. Neither trypsin nor collagenases dispersed epidermal cells."} {"id": "PMID:165788", "title": "Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor.", "content": "The first case of metastatic cystosarcoma phylloides in an adolescent is reported. This case also represents the first reported response of this tumor to chemotherapy and irradiation. This tumor showed an unusually rapid rate of cell division probably making it more susceptible to these agents. The importance of an early diagnosis and definitive excision is stressed.", "contents": "Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor. The first case of metastatic cystosarcoma phylloides in an adolescent is reported. This case also represents the first reported response of this tumor to chemotherapy and irradiation. This tumor showed an unusually rapid rate of cell division probably making it more susceptible to these agents. The importance of an early diagnosis and definitive excision is stressed."} {"id": "PMID:165789", "title": "Factors determining successful liver preservation for transplantation.", "content": "Auxiliary liver allotransplants will survive for relatively long periods of time after 24 hour hypothermic (10-12C), pulsatile perfusion. The best perfusate was a silica gel fraction of dog plasma with added potassium chloride gel made hyperosmolar with glucose. Further improvement could be achieved with added allopurinol and methylprednisolone. Nonpulsatile flow or lower temperatures were less effective preservation techniques.", "contents": "Factors determining successful liver preservation for transplantation. Auxiliary liver allotransplants will survive for relatively long periods of time after 24 hour hypothermic (10-12C), pulsatile perfusion. The best perfusate was a silica gel fraction of dog plasma with added potassium chloride gel made hyperosmolar with glucose. Further improvement could be achieved with added allopurinol and methylprednisolone. Nonpulsatile flow or lower temperatures were less effective preservation techniques."} {"id": "PMID:165790", "title": "Treatment of intra-abdominal and abdominal wall desmoid tumors with drugs that affect the metabolism of cyclic 3',5'-adenosine monophosphate.", "content": "A female patient with Gardner's syndrome was treated with delta1-testololactone (200 mg daily) because of growth of a large desmoid tumor in the pelvis and lower abdomen and a tumor in a scar from a previous laparotomy. There was also pain and swelling of the left leg. An immediate effect of the drug therapy was complete relief of pain followed shortly thereafter by disappearance of the edema of the leg. After two months, the numerous sebaceous cysts were less prominent. The gross measurements of the diameter of the pelvic and lower abdominal tumor clearly demonstrated tumor shrinkage following therapy. Small polyps scattered over the rectal mucosa and numerous osteomata were not demonstrably affected. After one year of treatment with delta1-testololactone, a laparotomy for partial small bowel obstruction was necessary. Obstruction was caused by the involvement of small bowel mesentery and the bowel itself in a contracted residuum of dense fibrous tissue. Substitution of theophylline and chlorothiazide for the testololactone in Januray 1974 was followed by further diminution of the measurable abdominal and pelvic desmoids. All of these compounds synergize the action of 3',5'-adenosine monophosphate and at least the latter two may function by inhibiting the action of 3',5'-adenosine monophosphate diesterase.", "contents": "Treatment of intra-abdominal and abdominal wall desmoid tumors with drugs that affect the metabolism of cyclic 3',5'-adenosine monophosphate. A female patient with Gardner's syndrome was treated with delta1-testololactone (200 mg daily) because of growth of a large desmoid tumor in the pelvis and lower abdomen and a tumor in a scar from a previous laparotomy. There was also pain and swelling of the left leg. An immediate effect of the drug therapy was complete relief of pain followed shortly thereafter by disappearance of the edema of the leg. After two months, the numerous sebaceous cysts were less prominent. The gross measurements of the diameter of the pelvic and lower abdominal tumor clearly demonstrated tumor shrinkage following therapy. Small polyps scattered over the rectal mucosa and numerous osteomata were not demonstrably affected. After one year of treatment with delta1-testololactone, a laparotomy for partial small bowel obstruction was necessary. Obstruction was caused by the involvement of small bowel mesentery and the bowel itself in a contracted residuum of dense fibrous tissue. Substitution of theophylline and chlorothiazide for the testololactone in Januray 1974 was followed by further diminution of the measurable abdominal and pelvic desmoids. All of these compounds synergize the action of 3',5'-adenosine monophosphate and at least the latter two may function by inhibiting the action of 3',5'-adenosine monophosphate diesterase."} {"id": "PMID:165791", "title": "Cancer of the bile ducts associated with ulcerative colitis.", "content": "Thirteen patients with bile duct cancer (excluding gallbladder) and associated chronic ulcerative colitis (CUC) were seen at the Mayo Clinic from 1935 through 1973. Most patients had initial symptoms of severe diarrhea and bleeding, followed by a pattern of mild-to-moderate disease with exacerbations and remissions. Three patients had especially severe symptoms and underwent total colectomy (1 patient) or proctocolectomy (2 patients) an average of 15.7 years from onset of CUC symptoms. Anorexia, followed rapidly by the development of progressive jaundice (or a sudden deterioration when liver disease was already present), marked the onset of symptoms of bile duct cancer in the 13 patients. The overall mean duration from onset of CUC to development of symptoms of bile duct cancer was 19 years. The patients in whom colitis was managed by proctocolectomy or total abdominal colectomy developed symptoms of bile duct cancer an average of 9.4 years after colectomy. When cancer was diagnosed, the tumor had spread beyond the bile ducts in 10 patients. The tumors were difficult to identify and often infiltrated the hepatic hilus. The present series and review of the literature suggest that the relationship between CUC and bile duct cancer is more than a chance occurrence. The carcinoma has an onset approximately 3 decades earlier than does carcinoma of the bile ducts without CUC. Surgical removal of the diseased colon and mode of medical management of the unresected colon have no relationship to the subsequent development of carcinoma of the bile ducts; neither does the extent or severity of the colonic disease. The prognosis of carcinoma of the bile ducts unfortunately continues to be dismal.", "contents": "Cancer of the bile ducts associated with ulcerative colitis. Thirteen patients with bile duct cancer (excluding gallbladder) and associated chronic ulcerative colitis (CUC) were seen at the Mayo Clinic from 1935 through 1973. Most patients had initial symptoms of severe diarrhea and bleeding, followed by a pattern of mild-to-moderate disease with exacerbations and remissions. Three patients had especially severe symptoms and underwent total colectomy (1 patient) or proctocolectomy (2 patients) an average of 15.7 years from onset of CUC symptoms. Anorexia, followed rapidly by the development of progressive jaundice (or a sudden deterioration when liver disease was already present), marked the onset of symptoms of bile duct cancer in the 13 patients. The overall mean duration from onset of CUC to development of symptoms of bile duct cancer was 19 years. The patients in whom colitis was managed by proctocolectomy or total abdominal colectomy developed symptoms of bile duct cancer an average of 9.4 years after colectomy. When cancer was diagnosed, the tumor had spread beyond the bile ducts in 10 patients. The tumors were difficult to identify and often infiltrated the hepatic hilus. The present series and review of the literature suggest that the relationship between CUC and bile duct cancer is more than a chance occurrence. The carcinoma has an onset approximately 3 decades earlier than does carcinoma of the bile ducts without CUC. Surgical removal of the diseased colon and mode of medical management of the unresected colon have no relationship to the subsequent development of carcinoma of the bile ducts; neither does the extent or severity of the colonic disease. The prognosis of carcinoma of the bile ducts unfortunately continues to be dismal."} {"id": "PMID:165792", "title": "Occult adrenal insufficiency in surgical patients.", "content": "Eight patients admitted to a University hospital with acute surgical problems and related adrenal insufficiency were reviewed and three are presented in detail. Surgical stress and continued sepsis played major roles in the lack of responsiveness to usual modes of therapy until the adrenal insufficiency was corrected. The patients fell into three major clinical categories of adrenal insufficiency. Chronic illness and sepsis are shown to affect steroid production and metabolism, as well as adrenal responsiveness to ACTH. Pharmacologic amounts of steroids are often needed in patients with shock, gram negative sepsis and prolonged illnesses, even if normal or elevated serum cortisols are present. Therapeutic trials of cortisol administration are shown to be confusing when not accompanied by easily performed diagnostic tests of adrenal function. It is emphasized that a pretreatment serum cortisol should be obtained whenever possible. The evaluation of adrenal function is of lifelong importance to the patient.", "contents": "Occult adrenal insufficiency in surgical patients. Eight patients admitted to a University hospital with acute surgical problems and related adrenal insufficiency were reviewed and three are presented in detail. Surgical stress and continued sepsis played major roles in the lack of responsiveness to usual modes of therapy until the adrenal insufficiency was corrected. The patients fell into three major clinical categories of adrenal insufficiency. Chronic illness and sepsis are shown to affect steroid production and metabolism, as well as adrenal responsiveness to ACTH. Pharmacologic amounts of steroids are often needed in patients with shock, gram negative sepsis and prolonged illnesses, even if normal or elevated serum cortisols are present. Therapeutic trials of cortisol administration are shown to be confusing when not accompanied by easily performed diagnostic tests of adrenal function. It is emphasized that a pretreatment serum cortisol should be obtained whenever possible. The evaluation of adrenal function is of lifelong importance to the patient."} {"id": "PMID:165793", "title": "Herpetic tracheobronchitis. Cytologic and virologic detection.", "content": "Tracheobronchitis due to herpes simplex virus is a well-recognized finding in cases of burns, debilitation, or immunosuppression. Nearly all reported cases have been diagnosed at necropsy despite the possibility for clinical detection of such infections by exfoliative cytological studies, virus isolation and identification, or both. The present report details the cytologic and virologic diagnosis of herpetic tracheobronchitis in a patient with carcinoma of the lung and alcoholic fatty liver. Respiratory cells with herpetic infection cytologically showed less tendency to multinucleation than the characteristic herpes-infected cells of squamous epithelium, which may be a source of diagnostic confusion.", "contents": "Herpetic tracheobronchitis. Cytologic and virologic detection. Tracheobronchitis due to herpes simplex virus is a well-recognized finding in cases of burns, debilitation, or immunosuppression. Nearly all reported cases have been diagnosed at necropsy despite the possibility for clinical detection of such infections by exfoliative cytological studies, virus isolation and identification, or both. The present report details the cytologic and virologic diagnosis of herpetic tracheobronchitis in a patient with carcinoma of the lung and alcoholic fatty liver. Respiratory cells with herpetic infection cytologically showed less tendency to multinucleation than the characteristic herpes-infected cells of squamous epithelium, which may be a source of diagnostic confusion."} {"id": "PMID:165794", "title": "Recovery from encephalomyelitis caused by Herpesvirus simiae. Report of a case.", "content": "A 29-year-old monkey handler developed an acute encephalomyelitis with neuromuscular dysfunction that progressed to respiratory arrest on the 18th day of illness. Thereafter, with supportive care, the patient's condition improved steadily. The titer of neutralizing antibodies to H simiae rose from 1:4 (eighth day of illness) to 1:512 (47th day of illness). Apparently the fifth known survivor of H simiae (herpesvirus B) encephalomyelitis, this patient is also remarkable because of virtually complete recovery, apparently the second documented instance of a good outcome.", "contents": "Recovery from encephalomyelitis caused by Herpesvirus simiae. Report of a case. A 29-year-old monkey handler developed an acute encephalomyelitis with neuromuscular dysfunction that progressed to respiratory arrest on the 18th day of illness. Thereafter, with supportive care, the patient's condition improved steadily. The titer of neutralizing antibodies to H simiae rose from 1:4 (eighth day of illness) to 1:512 (47th day of illness). Apparently the fifth known survivor of H simiae (herpesvirus B) encephalomyelitis, this patient is also remarkable because of virtually complete recovery, apparently the second documented instance of a good outcome."} {"id": "PMID:165795", "title": "A review of REM sleep deprivation.", "content": "Studies on the behavioral consequences of rapid eye movement (REM) sleep deprivation in animals and humans are critically reviewed. In animals, converging evidence--some reasonably well controlled--indicates that REM sleep deprivation probably heightens central neural excitability and increased motivational behavior, but has nuclear or inconclusive effects on learning. In humans, evidence indicates that REM sleep deprivation is not dream deprivation and is not harmful to schizophrenic, depressed, or healthy subjects. Controversy continues about whether or not (some) schizophrenic patients respond abnormally to REM sleep deprivation by having no REM rebound. Controlled but unconfirmed work indicates that that endogenous, but not reactive, depressive patients are improved by REM sleep deprivation, a finding consistent with the animal behavioral consequences of the procedure and with the unique REM-depriving properties of efficacious antidepressant drugs.", "contents": "A review of REM sleep deprivation. Studies on the behavioral consequences of rapid eye movement (REM) sleep deprivation in animals and humans are critically reviewed. In animals, converging evidence--some reasonably well controlled--indicates that REM sleep deprivation probably heightens central neural excitability and increased motivational behavior, but has nuclear or inconclusive effects on learning. In humans, evidence indicates that REM sleep deprivation is not dream deprivation and is not harmful to schizophrenic, depressed, or healthy subjects. Controversy continues about whether or not (some) schizophrenic patients respond abnormally to REM sleep deprivation by having no REM rebound. Controlled but unconfirmed work indicates that that endogenous, but not reactive, depressive patients are improved by REM sleep deprivation, a finding consistent with the animal behavioral consequences of the procedure and with the unique REM-depriving properties of efficacious antidepressant drugs."} {"id": "PMID:165796", "title": "REM sleep reduction effects on depression syndromes.", "content": "Thirty-four endogenous and 18 reactive, depressed patients (hospitalized and nonschizophrenic) were treated in a double-blind, crossover study of the hypothesis that rapid eye movement (REM) sleep reduction (by awakenings) relieves depression. In the endogenous group-but not in the reactive group-subjects deprived of REM sleep for three weeks improved significantly more than control subjects awakened from non-REM sleep. Therapeutic efficacy of REM sleep reduction appeared similar to reported efficacy of imipramine hydrochloride treatment of depression. Eight of nine endogenous patients, unimproved by REM sleep deprivation, did not improve with imipramine. Results suggested (1) that substantial REM sleep reduction has antidepressant activity, and (2) since imipramine and other drug antidepressants reduce REM sleep much more so than nonantidepressant drugs, that an antidepressant \"mechanism\" of drugs resides in their capacity to substantially reduce REM sleep.", "contents": "REM sleep reduction effects on depression syndromes. Thirty-four endogenous and 18 reactive, depressed patients (hospitalized and nonschizophrenic) were treated in a double-blind, crossover study of the hypothesis that rapid eye movement (REM) sleep reduction (by awakenings) relieves depression. In the endogenous group-but not in the reactive group-subjects deprived of REM sleep for three weeks improved significantly more than control subjects awakened from non-REM sleep. Therapeutic efficacy of REM sleep reduction appeared similar to reported efficacy of imipramine hydrochloride treatment of depression. Eight of nine endogenous patients, unimproved by REM sleep deprivation, did not improve with imipramine. Results suggested (1) that substantial REM sleep reduction has antidepressant activity, and (2) since imipramine and other drug antidepressants reduce REM sleep much more so than nonantidepressant drugs, that an antidepressant \"mechanism\" of drugs resides in their capacity to substantially reduce REM sleep."} {"id": "PMID:165797", "title": "A neuroendocrine predisposition for homosexuality in men.", "content": "In male rats, androgen deficiency during a critical hypothalamic organizational period was shown to give rise to a predominantly female-differentiated brain, homosexual behavior, and demonstration of a positive estrogen feedback effect. A positive estrogen feedback effect was also induced in intact homosexual men in contrast to intact heterosexual and bisexual men. Thus in 21 homosexual men an intravenous injection of 20 mg Presomen (Premarin) produced a significant decrease of serum LH levels followed by an increase above initial LH values. In 20 heterosexual and in five bisexual men, by contrast, intravenous estrogen administration, while producing a significant decrease of the serum LH level, was not followed by an increase above the initial LH values. Using a radioimmunoassay, plasma testosterone levels and 24-hr urinary excretions of unconjugated testosterone of adult homosexual men were found to be in the normal range as observed in heterosexual men. This finding suggests that homosexual men possess a predominantly female-differentiated brain which may be activated to homosexual behavior by normal or approximately normal androgen levels in adulthood.", "contents": "A neuroendocrine predisposition for homosexuality in men. In male rats, androgen deficiency during a critical hypothalamic organizational period was shown to give rise to a predominantly female-differentiated brain, homosexual behavior, and demonstration of a positive estrogen feedback effect. A positive estrogen feedback effect was also induced in intact homosexual men in contrast to intact heterosexual and bisexual men. Thus in 21 homosexual men an intravenous injection of 20 mg Presomen (Premarin) produced a significant decrease of serum LH levels followed by an increase above initial LH values. In 20 heterosexual and in five bisexual men, by contrast, intravenous estrogen administration, while producing a significant decrease of the serum LH level, was not followed by an increase above the initial LH values. Using a radioimmunoassay, plasma testosterone levels and 24-hr urinary excretions of unconjugated testosterone of adult homosexual men were found to be in the normal range as observed in heterosexual men. This finding suggests that homosexual men possess a predominantly female-differentiated brain which may be activated to homosexual behavior by normal or approximately normal androgen levels in adulthood."} {"id": "PMID:165798", "title": "Further evaluation of total pancreatectomy.", "content": "The results of 64 total pancreatectomies performed at the Mayo Clinic between 1942 and 1973 have been reviewed. Improvement in recent results as compared to the previously reported series is probably related to improvements in operative techniques and in selection of patients with more favorable malignant lesions. The recent results are more favorable than those reported for a group of comparable patients undergoing standard Whipple procedures for malignant lesions at this institution. Diabetes was easily managed in 76% of patients. Hypoglycemia due to insulin sensitivity is the major problem, and ketoacidosis seldom occurs. Recognition of this has resulted in better management of diabetes with relatively small doses of insulin. The sequels of long-standing diabetes do not appear to be a problem. Gastrointestinal tract hemorrhage has been greatly decreased through the use of more extensive gastric resection.", "contents": "Further evaluation of total pancreatectomy. The results of 64 total pancreatectomies performed at the Mayo Clinic between 1942 and 1973 have been reviewed. Improvement in recent results as compared to the previously reported series is probably related to improvements in operative techniques and in selection of patients with more favorable malignant lesions. The recent results are more favorable than those reported for a group of comparable patients undergoing standard Whipple procedures for malignant lesions at this institution. Diabetes was easily managed in 76% of patients. Hypoglycemia due to insulin sensitivity is the major problem, and ketoacidosis seldom occurs. Recognition of this has resulted in better management of diabetes with relatively small doses of insulin. The sequels of long-standing diabetes do not appear to be a problem. Gastrointestinal tract hemorrhage has been greatly decreased through the use of more extensive gastric resection."} {"id": "PMID:165799", "title": "[A change in the ultrastructure of frog spinal cord and motor neuron synapses during prolonged activation].", "content": "Motoneuron axosomatic synapses (AS) were shown to be larger than axodendritic (AD) synapses under anaesthesia. A 10 minute-long electrical stimulation both by low and high frequency caused enlargement of AS and AD synapses, it being the more pronounced the higher was the activation frequency. In all cases changes the AS synapses were more marked than those of AD synapses. On the bases of morphological and physiological data it was concluded that the changes of the synapse dimentions did not affect the synaptic transmission.", "contents": "[A change in the ultrastructure of frog spinal cord and motor neuron synapses during prolonged activation]. Motoneuron axosomatic synapses (AS) were shown to be larger than axodendritic (AD) synapses under anaesthesia. A 10 minute-long electrical stimulation both by low and high frequency caused enlargement of AS and AD synapses, it being the more pronounced the higher was the activation frequency. In all cases changes the AS synapses were more marked than those of AD synapses. On the bases of morphological and physiological data it was concluded that the changes of the synapse dimentions did not affect the synaptic transmission."} {"id": "PMID:165800", "title": "[A malignant variant of Abrikosov's tumor].", "content": "Three observations on granular-cell Abrikosov's tumours with locally destructive growth and polymorphism of cells (in 2 male and 1 female patients) located in soft tissues of a hand finger, under the skin of teh upper lip, and in soft tissues of the lumbar region are described. A critical survey of the literature is given.", "contents": "[A malignant variant of Abrikosov's tumor]. Three observations on granular-cell Abrikosov's tumours with locally destructive growth and polymorphism of cells (in 2 male and 1 female patients) located in soft tissues of a hand finger, under the skin of teh upper lip, and in soft tissues of the lumbar region are described. A critical survey of the literature is given."} {"id": "PMID:165801", "title": "[Fibroblast-fibroclast: The ultrastructural mechanisms of resorption of collagen fibers in involution of the connective tissue].", "content": "Using various experimental models (postpartum involution of the uterus, resolution of a subcutaneous scar which replaced the collagen implant and connective-tissue capsule following the removal of a foreign body) and electron-microscopy and histochemical methods of investigation intra- and extracellular resorption of th e collagenous fibres was extablished. The main role in this process was played by fibroblasts which uncer these conditions could funciton as fibroclasts phagocyting and idgesting in its cytoplasma collagenous fibrillas with the help of lysosomal enzymes. Desintegration of fibroclasts, enriching the medium with these enzymes, stimulated the extracellular lysis of the collagenous fibrillas. This lysis was particularly intensive in the presence of an inflammatory process, and even could take place before the intracellular resorption. In macrophages no intracellular lysis was observed, however, they could phagocyte denaturated collagen, deprived of structural orgainzation.", "contents": "[Fibroblast-fibroclast: The ultrastructural mechanisms of resorption of collagen fibers in involution of the connective tissue]. Using various experimental models (postpartum involution of the uterus, resolution of a subcutaneous scar which replaced the collagen implant and connective-tissue capsule following the removal of a foreign body) and electron-microscopy and histochemical methods of investigation intra- and extracellular resorption of th e collagenous fibres was extablished. The main role in this process was played by fibroblasts which uncer these conditions could funciton as fibroclasts phagocyting and idgesting in its cytoplasma collagenous fibrillas with the help of lysosomal enzymes. Desintegration of fibroclasts, enriching the medium with these enzymes, stimulated the extracellular lysis of the collagenous fibrillas. This lysis was particularly intensive in the presence of an inflammatory process, and even could take place before the intracellular resorption. In macrophages no intracellular lysis was observed, however, they could phagocyte denaturated collagen, deprived of structural orgainzation."} {"id": "PMID:165802", "title": "Hydrocephalus produced by the 6/94 virus; A parainfluenza type 1 isolate from multiple sclerosis brain tissue.", "content": "The 6/94 virus, parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced hydrocephalus in newborn Syrian hamsters. All animals developed clinical disease and died within a week. Ependymal cells lining the aqueduct of Sylvius became necrotic and fused, resulting in obstructive hydrocephalus. The 6/94 virus antigen was seen in ependyma and meninges. Paramyxovirus nucleocapsids were seen within cytoplasm of ependymal cells. Virus was recovered from hamster brains for only two days. Infectious virus could be recovered from brains grown in vitro as explants for 21 days. No evidence of rising hemagglutination-inhibiting antibody was noted for up to one month after infection. Intraperitoneal or subcutaneous injection of 6/94 virus did not produce hydrocephalus. HA2 virus and the temperature sensitive mutant of HA2 virus failed to produce hydrocephalus, while Sendai virus caused lesions similar to those of 6/94 virus.", "contents": "Hydrocephalus produced by the 6/94 virus; A parainfluenza type 1 isolate from multiple sclerosis brain tissue. The 6/94 virus, parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced hydrocephalus in newborn Syrian hamsters. All animals developed clinical disease and died within a week. Ependymal cells lining the aqueduct of Sylvius became necrotic and fused, resulting in obstructive hydrocephalus. The 6/94 virus antigen was seen in ependyma and meninges. Paramyxovirus nucleocapsids were seen within cytoplasm of ependymal cells. Virus was recovered from hamster brains for only two days. Infectious virus could be recovered from brains grown in vitro as explants for 21 days. No evidence of rising hemagglutination-inhibiting antibody was noted for up to one month after infection. Intraperitoneal or subcutaneous injection of 6/94 virus did not produce hydrocephalus. HA2 virus and the temperature sensitive mutant of HA2 virus failed to produce hydrocephalus, while Sendai virus caused lesions similar to those of 6/94 virus."} {"id": "PMID:165803", "title": "Atypical myopathy with myofibrillar aggregates.", "content": "An autopsy of a 23-year-old woman with progressive muscular weakness and wasting showed a unique muscle abnormality with segmental involvement of individual fibers by peculiar inclusions. Electron microscopically, these inclusions resembled cytoplasmic bodies, being formed of two concentric zones of filamentous materials. They seemed to arise from filaments of myofibrils that were fragmented and highly disorganized in affected areas.", "contents": "Atypical myopathy with myofibrillar aggregates. An autopsy of a 23-year-old woman with progressive muscular weakness and wasting showed a unique muscle abnormality with segmental involvement of individual fibers by peculiar inclusions. Electron microscopically, these inclusions resembled cytoplasmic bodies, being formed of two concentric zones of filamentous materials. They seemed to arise from filaments of myofibrils that were fragmented and highly disorganized in affected areas."} {"id": "PMID:165805", "title": "Lipoproteins in atherosclerotic lesions. Localization by immunofluorescence of apo-low density lipoproteins in human atherosclerotic arteries from normal and hyperlipoproteinemics.", "content": "Using immunofluorescence techniques, apoLDL, the major protein component of human plasma low and very low density lipoproteins was localized in athersclerotic lesions from the aorta, coronary, and carotid arteries in human normolipoproteinemic, type II, and type IV hyperlipoproteinemics. Although no apoLDL was detected in uninvolved arteries, atheromas from advanced lesions as well as certain collagen and elastic fibers from both fatty streaks and advanced lesions were positive for apoLDL. This localization pattern was the same in each lipemic group, except for the presence of apoLDL in some intimal cells from type II cases. However, extensiveness of apoLDL localization was greatest in the type II group, but equal in the normolipemic and type II group. This may be explained by the high concentration gradient between plasma and tissue for apoLDL in the type II group.", "contents": "Lipoproteins in atherosclerotic lesions. Localization by immunofluorescence of apo-low density lipoproteins in human atherosclerotic arteries from normal and hyperlipoproteinemics. Using immunofluorescence techniques, apoLDL, the major protein component of human plasma low and very low density lipoproteins was localized in athersclerotic lesions from the aorta, coronary, and carotid arteries in human normolipoproteinemic, type II, and type IV hyperlipoproteinemics. Although no apoLDL was detected in uninvolved arteries, atheromas from advanced lesions as well as certain collagen and elastic fibers from both fatty streaks and advanced lesions were positive for apoLDL. This localization pattern was the same in each lipemic group, except for the presence of apoLDL in some intimal cells from type II cases. However, extensiveness of apoLDL localization was greatest in the type II group, but equal in the normolipemic and type II group. This may be explained by the high concentration gradient between plasma and tissue for apoLDL in the type II group."} {"id": "PMID:165807", "title": "Collagen metabolism in rat lungs during chronic intermittent exposure to oxygen.", "content": "Collagen metabolism was studied in rat lungs during prolonged intermittent exposure to oxygen. After an initial of 2-d exposure to oxygen, the rats alternately breathed air and oxygen in 24-h periods up to 30 d. Lung histology showed perivascular edema as an early sign of oxygen toxicity. Increased capillary permeability was followed by a marked perivascular leukocytosis that was prominent between the 5th and 11th d of the treatment. During the further course of the experiment, the inflammatory response gradually diminished, and finally a network of collagen fibres filled the perivascular areas. The inflammatory process elevated the amounts of DNA and RNA in lung tissue, and the ratio of RNA to DNA was maximal on the 5th day. Studies on metabolism of lung collagen with intraperitoneally injected 3H-proline as label showed that, after the initial inflammatory reaction, both synthesis and degration of collagen were increased in oxygen-treated lungs. The increase in synthesis exceeded the rise in degradation and, therefore, collagen was accumulated. The activation of lung collagen synthesis coincided in time with a rise in the activity of lung protocollagen proline hydroxylase.", "contents": "Collagen metabolism in rat lungs during chronic intermittent exposure to oxygen. Collagen metabolism was studied in rat lungs during prolonged intermittent exposure to oxygen. After an initial of 2-d exposure to oxygen, the rats alternately breathed air and oxygen in 24-h periods up to 30 d. Lung histology showed perivascular edema as an early sign of oxygen toxicity. Increased capillary permeability was followed by a marked perivascular leukocytosis that was prominent between the 5th and 11th d of the treatment. During the further course of the experiment, the inflammatory response gradually diminished, and finally a network of collagen fibres filled the perivascular areas. The inflammatory process elevated the amounts of DNA and RNA in lung tissue, and the ratio of RNA to DNA was maximal on the 5th day. Studies on metabolism of lung collagen with intraperitoneally injected 3H-proline as label showed that, after the initial inflammatory reaction, both synthesis and degration of collagen were increased in oxygen-treated lungs. The increase in synthesis exceeded the rise in degradation and, therefore, collagen was accumulated. The activation of lung collagen synthesis coincided in time with a rise in the activity of lung protocollagen proline hydroxylase."} {"id": "PMID:165808", "title": "Histologic types and possible initial stages in early gastric carcinoma.", "content": "Among 2003 gastric specimens from 301 patients, diagnosis for carcinoma was made in 45 cases. Examination of resection preparations revealed 36 cases of deep invasive stomach carcinoma and 9 cases of early gastric cancer confined to mucosa and/or submucosa. Carcinomatous proliferations limited to mucosa or submucosa are classified in three histologic types: intestinal (adeno), mucocellular (signet ring cell), and anaplastic (solid) type of early gastric cancer. Mixed types have been found combining the first and the second, or the second and the third type. One case presented a mixture of all three types. Possible precursor or initial stages of all three types were found in further 31 biopsies. Some of them were glandular lesions in superficial parts of the mucosa; this kind has been described previously as possible preneoplastic stage of the intestinal type of early gastric cancer. \"Signet ring cell drippings\" from lower parts of tubule necks were recorded as an initial form of the signet ring cell type. The process is interpreted as detaching of isolated signet ring cells from a gland neck zone in progressing atypical transformation. An early neoplastic stage of the anaplastic (solid) type of early gastric cancer is identified in the \"gland neck dysplasia\" located exclusively in the antrum between surface mucosa and antrum glands. This lesion appears rich in cells and stretched like a broad ribbon. Early gastric cancer of this third type will arise in the very same location. Conclusions from formal histogenesis suggest that the signet ring cell type and the anaplastic (solid) type of early gastric cancer might start in the lower part of tubule necks. In consequence, the neck region of gastric glands could be the critical field of malignant transformation in the gastric mucosa. Long-term follow-up studies will be needed to verify these observations and their interpretation.", "contents": "Histologic types and possible initial stages in early gastric carcinoma. Among 2003 gastric specimens from 301 patients, diagnosis for carcinoma was made in 45 cases. Examination of resection preparations revealed 36 cases of deep invasive stomach carcinoma and 9 cases of early gastric cancer confined to mucosa and/or submucosa. Carcinomatous proliferations limited to mucosa or submucosa are classified in three histologic types: intestinal (adeno), mucocellular (signet ring cell), and anaplastic (solid) type of early gastric cancer. Mixed types have been found combining the first and the second, or the second and the third type. One case presented a mixture of all three types. Possible precursor or initial stages of all three types were found in further 31 biopsies. Some of them were glandular lesions in superficial parts of the mucosa; this kind has been described previously as possible preneoplastic stage of the intestinal type of early gastric cancer. \"Signet ring cell drippings\" from lower parts of tubule necks were recorded as an initial form of the signet ring cell type. The process is interpreted as detaching of isolated signet ring cells from a gland neck zone in progressing atypical transformation. An early neoplastic stage of the anaplastic (solid) type of early gastric cancer is identified in the \"gland neck dysplasia\" located exclusively in the antrum between surface mucosa and antrum glands. This lesion appears rich in cells and stretched like a broad ribbon. Early gastric cancer of this third type will arise in the very same location. Conclusions from formal histogenesis suggest that the signet ring cell type and the anaplastic (solid) type of early gastric cancer might start in the lower part of tubule necks. In consequence, the neck region of gastric glands could be the critical field of malignant transformation in the gastric mucosa. Long-term follow-up studies will be needed to verify these observations and their interpretation."} {"id": "PMID:165823", "title": "Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis.", "content": "Proline hydroxylase activity and collagen content were determined in atherosclerotic plaque, fatty streak, and normal tissue from aortas of White Carneau pigeons with naturally-occurring of cholesterol-aggravated atherosclerosis. Little increase in collagen content or proline hydroxylase activity occurred in fatty streaks or plaques from birds with cholesterol-aggravated atherosclerosis. This is consistent with the morphologic observation of the presence of little or no \"fibromuscular cap\" in these cholesterol-aggravated lesions. Both normal and plaque tissue from arotas of birds with naturally-occurring atherosclerosis contained more collagen than did similar tissues from control birds or birds with cholesterol-aggravated lesions. The largest proportion of this increase in collagen content probably represented an age effect since it occurred in normal as well as atherosclerotic tissue. Plaques from aortas of birds with naturally-occurring atherosclerosis did contain, however, significantly more collagen than normal tissue from the same aortas. This is consistent with the presence of a prominent \"fibromuscular cap\" in these naturally-occurring lesions. Proline hydroxylase activity was less in these lesions than in normal tissue from the same aortas. Consequently increased proline hydroxylase activity and collagen content are not greatly altered in association with development of cholesterol-aggravated atherosclerotic lesions in pigeons. On the other hand, well-developed naturally-occurring lesions contained increased concentrations of collagen but showed no increase proline hydroxylase activity. This is not to say though, that active collagen synthesis and presukably increased proline hydroxylase activity did not take place at some point in the development of these naturally-occurring lesions.", "contents": "Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis. Proline hydroxylase activity and collagen content were determined in atherosclerotic plaque, fatty streak, and normal tissue from aortas of White Carneau pigeons with naturally-occurring of cholesterol-aggravated atherosclerosis. Little increase in collagen content or proline hydroxylase activity occurred in fatty streaks or plaques from birds with cholesterol-aggravated atherosclerosis. This is consistent with the morphologic observation of the presence of little or no \"fibromuscular cap\" in these cholesterol-aggravated lesions. Both normal and plaque tissue from arotas of birds with naturally-occurring atherosclerosis contained more collagen than did similar tissues from control birds or birds with cholesterol-aggravated lesions. The largest proportion of this increase in collagen content probably represented an age effect since it occurred in normal as well as atherosclerotic tissue. Plaques from aortas of birds with naturally-occurring atherosclerosis did contain, however, significantly more collagen than normal tissue from the same aortas. This is consistent with the presence of a prominent \"fibromuscular cap\" in these naturally-occurring lesions. Proline hydroxylase activity was less in these lesions than in normal tissue from the same aortas. Consequently increased proline hydroxylase activity and collagen content are not greatly altered in association with development of cholesterol-aggravated atherosclerotic lesions in pigeons. On the other hand, well-developed naturally-occurring lesions contained increased concentrations of collagen but showed no increase proline hydroxylase activity. This is not to say though, that active collagen synthesis and presukably increased proline hydroxylase activity did not take place at some point in the development of these naturally-occurring lesions."} {"id": "PMID:165824", "title": "The effect of nicotinic acid on the metabolism of the plasma lipoproteins of rhesus monkeys.", "content": "The effect of nicotinic acid was investigated in Rhesus monkeys. Subcutaneous injections of nicotinic acid lower the plasma very low density lipoprotein (VVLDL) and low density lipoprotein (HDL) concentration. The fall in LDL concentration is not accompained by any change in the lipid or protein composition of either lipoprotein. Analysis by Sephadex gel chromatography and polyacrylamide-gel electrophoresis showed that the proteins of monkey VLDL and LDL are qualitatively similar to those of human VLDL and LDL, although there are differences in the proportions of the various proteins present in the two species. Subcutaneous injections of nicotinic acid diminish the maximum incorporation of 14C from [14C]threonine into VLDL and LDL apoproteins, but have no effect on incorporation into albumin or HDL apoprotein. Peak incorporations into the apo-B and apo-C of VLDL are diminished to about equal extents by nicotinic acid. Comparison of the amount of 14C lost from apo-B of VLDL after the peak of incorporation, with that gained by apo-B of LDL during the same period, suggests that some of the circulating apo-B of LDL IS DERIVED FROM SOURCES OTHER THAN CIRCULATING VLDL.", "contents": "The effect of nicotinic acid on the metabolism of the plasma lipoproteins of rhesus monkeys. The effect of nicotinic acid was investigated in Rhesus monkeys. Subcutaneous injections of nicotinic acid lower the plasma very low density lipoprotein (VVLDL) and low density lipoprotein (HDL) concentration. The fall in LDL concentration is not accompained by any change in the lipid or protein composition of either lipoprotein. Analysis by Sephadex gel chromatography and polyacrylamide-gel electrophoresis showed that the proteins of monkey VLDL and LDL are qualitatively similar to those of human VLDL and LDL, although there are differences in the proportions of the various proteins present in the two species. Subcutaneous injections of nicotinic acid diminish the maximum incorporation of 14C from [14C]threonine into VLDL and LDL apoproteins, but have no effect on incorporation into albumin or HDL apoprotein. Peak incorporations into the apo-B and apo-C of VLDL are diminished to about equal extents by nicotinic acid. Comparison of the amount of 14C lost from apo-B of VLDL after the peak of incorporation, with that gained by apo-B of LDL during the same period, suggests that some of the circulating apo-B of LDL IS DERIVED FROM SOURCES OTHER THAN CIRCULATING VLDL."} {"id": "PMID:165828", "title": "An examination of octanol and octanal metabolism to octanoic acid by horse liver alcohol dehydrogenase.", "content": "The kinetics of the horse liver alcohol dehydrogenase (alcohol: NAD+ oxidoreductase EC 1.1.1.1) catalyzed metabolism of octanol and octanal to octanoic acid have been examined. On incubation of octanol with horse liver alcohol dehydrogenase in the presence of NAD+, NADH as well as octanal and octanoic acid were seen as the initial products. However, on continued incubation, the octanal concentration progressively decreased to where only negligible quantities were present in the incubation after 10 min. The production of NADH was biphasic. An initial phase was followed in about 2 min with a slower but linear rate of NADH production. The production of octanoic acid was approximately linear throughout the 10 min incubation period. Since octanal is an intermediate in the oxidation of octanol to octanoic acid, the ability of semicarbazide to inhibit the metabolism of octanol to octanoic acid was examined. At a concentration of semicarbazide which was 63 times the concentration of octanol in the incubation media, the rate of formation of octanoic acid was inhibited by only 30%. The results of these experiments suggest that in the oxidation of octanol to octanoic acid a portion of the octanal formed from octanol is not released from the enzyme but, in the presence of NAD+, is oxidized to octanoic acid.", "contents": "An examination of octanol and octanal metabolism to octanoic acid by horse liver alcohol dehydrogenase. The kinetics of the horse liver alcohol dehydrogenase (alcohol: NAD+ oxidoreductase EC 1.1.1.1) catalyzed metabolism of octanol and octanal to octanoic acid have been examined. On incubation of octanol with horse liver alcohol dehydrogenase in the presence of NAD+, NADH as well as octanal and octanoic acid were seen as the initial products. However, on continued incubation, the octanal concentration progressively decreased to where only negligible quantities were present in the incubation after 10 min. The production of NADH was biphasic. An initial phase was followed in about 2 min with a slower but linear rate of NADH production. The production of octanoic acid was approximately linear throughout the 10 min incubation period. Since octanal is an intermediate in the oxidation of octanol to octanoic acid, the ability of semicarbazide to inhibit the metabolism of octanol to octanoic acid was examined. At a concentration of semicarbazide which was 63 times the concentration of octanol in the incubation media, the rate of formation of octanoic acid was inhibited by only 30%. The results of these experiments suggest that in the oxidation of octanol to octanoic acid a portion of the octanal formed from octanol is not released from the enzyme but, in the presence of NAD+, is oxidized to octanoic acid."} {"id": "PMID:165829", "title": "The separation, properties and possible subunit composition of adenosine 3',5'-monophosphate-dependent protein kinases in brown adipose tissue.", "content": "Two 8.5-S protein kinases (ATP : protein phosphotransferase EC 2.7.1.37) and one 6.6-S protein kinase were purified 500--1000-fold from the acid-soluble fraction of brown adipose tissue. The catalytic properties of the kinases were similar. Each kinase was activated by cyclic AMP and had two components of cyclic AMP binding. In the presence of 200 nM cyclic AMP, undissociated kinase activity sedimented at 7.7 or 5.5 S. Free catalytic activity (3.2 S) could be detected but was unstable. Free regulatory units could not be detected. The 8.5-S protein kinase was dissociated by freezing and thawing to a 7.7-S variety with loss of the higher affinity component of binding. The 7.7-S kinase was sedimented through linear gradients of sucrose containing different concentrations of cyclic AMP. At each concentration, kinase activity lost from the holoenzyme peak (% of original) was identical with the amount of cyclic AMP bound at equilibrium (% oof maximum). Similar experiments on the 8.5-S kinase showed that the binding component with higher affinity was not associated with the release of catalytic activity. The results were consistent with the propostal that the kinases isolated contained one more cyclic AMP binding subunit than catalytic subunit (3 : 2 for 8.5 S and 2 : 1 for 6.6 S) and that this extra subunit was released to give an equal number of subunits of each type before catalytic activity was liberated.", "contents": "The separation, properties and possible subunit composition of adenosine 3',5'-monophosphate-dependent protein kinases in brown adipose tissue. Two 8.5-S protein kinases (ATP : protein phosphotransferase EC 2.7.1.37) and one 6.6-S protein kinase were purified 500--1000-fold from the acid-soluble fraction of brown adipose tissue. The catalytic properties of the kinases were similar. Each kinase was activated by cyclic AMP and had two components of cyclic AMP binding. In the presence of 200 nM cyclic AMP, undissociated kinase activity sedimented at 7.7 or 5.5 S. Free catalytic activity (3.2 S) could be detected but was unstable. Free regulatory units could not be detected. The 8.5-S protein kinase was dissociated by freezing and thawing to a 7.7-S variety with loss of the higher affinity component of binding. The 7.7-S kinase was sedimented through linear gradients of sucrose containing different concentrations of cyclic AMP. At each concentration, kinase activity lost from the holoenzyme peak (% of original) was identical with the amount of cyclic AMP bound at equilibrium (% oof maximum). Similar experiments on the 8.5-S kinase showed that the binding component with higher affinity was not associated with the release of catalytic activity. The results were consistent with the propostal that the kinases isolated contained one more cyclic AMP binding subunit than catalytic subunit (3 : 2 for 8.5 S and 2 : 1 for 6.6 S) and that this extra subunit was released to give an equal number of subunits of each type before catalytic activity was liberated."} {"id": "PMID:165830", "title": "The effect of ADP, calcium and some inhibitors of platelet aggregation on protein phosphokinases from human blood platelets.", "content": "A protein phosphokinase (ATP: protein phosphotransferase EC 2.7.1.37) which is stimulated by 3',5'-cyclic adenosine monophosphate (cyclic AMP) has been partially purified from both the cytoplasmic and membrane fractions of human platelets. The kinetics of both enzymes preparations are similar in respect to cyclic AMP, ATP, ADP and AMP. 5-10-minus 7 M cyclic AMP stimulated both preparations by approximately 100%. Both ADP and AMP at a concentration of 5-10-minus 5 M inhibited protein phosphokinase activity of the soluble and membrane preparation by between 50% and 70%. The response of the two enzyme preparations to calcium differed. 10 mM Ca-2+ inhibited soluble protein phosphokinase activity approximately 80% both in the presence and absence of 5-10 minus 7 M cyclic AMP whereas the same concentrations of Ca-2+ inhibited the membrane-bound enzyme by approximately 60% in the presence of 5-10-minus 7 M cyclic AMP and 40% in the absence of cyclic AMP. This observation may be of importance in understanding the mechanism of platelet aggregation.", "contents": "The effect of ADP, calcium and some inhibitors of platelet aggregation on protein phosphokinases from human blood platelets. A protein phosphokinase (ATP: protein phosphotransferase EC 2.7.1.37) which is stimulated by 3',5'-cyclic adenosine monophosphate (cyclic AMP) has been partially purified from both the cytoplasmic and membrane fractions of human platelets. The kinetics of both enzymes preparations are similar in respect to cyclic AMP, ATP, ADP and AMP. 5-10-minus 7 M cyclic AMP stimulated both preparations by approximately 100%. Both ADP and AMP at a concentration of 5-10-minus 5 M inhibited protein phosphokinase activity of the soluble and membrane preparation by between 50% and 70%. The response of the two enzyme preparations to calcium differed. 10 mM Ca-2+ inhibited soluble protein phosphokinase activity approximately 80% both in the presence and absence of 5-10 minus 7 M cyclic AMP whereas the same concentrations of Ca-2+ inhibited the membrane-bound enzyme by approximately 60% in the presence of 5-10-minus 7 M cyclic AMP and 40% in the absence of cyclic AMP. This observation may be of importance in understanding the mechanism of platelet aggregation."} {"id": "PMID:165826", "title": "The porcine endothelial cell in tissue culture.", "content": "Endothelial cells from porcine aorta and inferior vena cava have been harvested, using trypsin, EDTA or collagenase, and grown in tissue culture. Growth-behaviour, cytology, scanning and electronmicroscopy findings are reported. It is hoped that this technique will prove useful in the investigation of atherosclerosis.", "contents": "The porcine endothelial cell in tissue culture. Endothelial cells from porcine aorta and inferior vena cava have been harvested, using trypsin, EDTA or collagenase, and grown in tissue culture. Growth-behaviour, cytology, scanning and electronmicroscopy findings are reported. It is hoped that this technique will prove useful in the investigation of atherosclerosis."} {"id": "PMID:165831", "title": "Hydrolysis of guanosine and adenosine 3',5'-monophosphates by rat blood.", "content": "Cyclic nucleotide phosphodiesterase activity was measured in whole blood, plasma, and suspensions of platelets and erythrocytes from rats. In fresh whole blood, apparent phosphodiesterase activity was low, but it rose strikingly during the hour after blood withdrawal. The apparent phosphodiesterase activity in platelet-free plasma showed no such increase, but that in platelet-enriched plasma increased in parallel with that in whole blood. The apparent phosphodiesterase activity of blood or of platelet-enriched plasma also was increased markedly by sonication. The increase in rat blood phosphodiesterase activity with aging thus appeared to be due to damage of platelets. Most of the phosphodiesterase activity in rat erythrocytes and platelets was located in the soluble fraction of sonicated preparations, but the total enzyme activities from the two sources exhibited marked differences in substrate specificity. With erythrocyte preparations, the rate of hydrolysis of muM concentrations of cyclic AMP was approx. 50 times that of cyclic GMP, while with platelet preparations, cyclic GMP was hydrolyzed about 20 times faster than cyclic AMP at muM levels. The activity of phosphodiesterase in platelets was much greater than that in erythrocytes at all concentrations of both substrates.", "contents": "Hydrolysis of guanosine and adenosine 3',5'-monophosphates by rat blood. Cyclic nucleotide phosphodiesterase activity was measured in whole blood, plasma, and suspensions of platelets and erythrocytes from rats. In fresh whole blood, apparent phosphodiesterase activity was low, but it rose strikingly during the hour after blood withdrawal. The apparent phosphodiesterase activity in platelet-free plasma showed no such increase, but that in platelet-enriched plasma increased in parallel with that in whole blood. The apparent phosphodiesterase activity of blood or of platelet-enriched plasma also was increased markedly by sonication. The increase in rat blood phosphodiesterase activity with aging thus appeared to be due to damage of platelets. Most of the phosphodiesterase activity in rat erythrocytes and platelets was located in the soluble fraction of sonicated preparations, but the total enzyme activities from the two sources exhibited marked differences in substrate specificity. With erythrocyte preparations, the rate of hydrolysis of muM concentrations of cyclic AMP was approx. 50 times that of cyclic GMP, while with platelet preparations, cyclic GMP was hydrolyzed about 20 times faster than cyclic AMP at muM levels. The activity of phosphodiesterase in platelets was much greater than that in erythrocytes at all concentrations of both substrates."} {"id": "PMID:165832", "title": "Purification and properties of a peptidase acting on a synthetic substrate for collagenase from monkey kidney.", "content": "A peptidase cleaving a synthetic substrate for collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (designated as PZ-peptide) has been purified extensively (about 5200-fold) from a soluble extract of monkey kidney with a view of carrying out studies on its possible physiological role. The purified PZ-peptidase appeared essentially free of collagenase, nonspecific protease and di- and tri-peptidase activities. The properties of the purified PZ-peptidase resemble very much the granuloma enzyme. It is optimally active around pH 7.0. Its apparent Km value for PZ-peptide is 0.72 mM and V is 10.1 mumol/mg protein/min. It is reversibly inhibited by p-hydroxymercuribenzoate and HgCl2, whereas iodoactetamide does not affect the enzyme activity. N-Ethylmaleimide inhibited the enzyme partially (50%). Heavy metals like Cu-2+, Cd-2+, Ag+, Pb-2+, Ni-2+, and Zn-2+ completely inhibited the enzyme activity, while the inhibition by Co-2+ was only partial. Fe-2+ did not exert any effect on the activity. The enzyme activity was completely inhibited by EDTA and was restored almost to the original value by metal ions like Mn-2+, Mg-2+, Ca-2+ and Ba-2+. The approximate molecular weight of the purified enzyme was estimated to be 56 000.", "contents": "Purification and properties of a peptidase acting on a synthetic substrate for collagenase from monkey kidney. A peptidase cleaving a synthetic substrate for collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (designated as PZ-peptide) has been purified extensively (about 5200-fold) from a soluble extract of monkey kidney with a view of carrying out studies on its possible physiological role. The purified PZ-peptidase appeared essentially free of collagenase, nonspecific protease and di- and tri-peptidase activities. The properties of the purified PZ-peptidase resemble very much the granuloma enzyme. It is optimally active around pH 7.0. Its apparent Km value for PZ-peptide is 0.72 mM and V is 10.1 mumol/mg protein/min. It is reversibly inhibited by p-hydroxymercuribenzoate and HgCl2, whereas iodoactetamide does not affect the enzyme activity. N-Ethylmaleimide inhibited the enzyme partially (50%). Heavy metals like Cu-2+, Cd-2+, Ag+, Pb-2+, Ni-2+, and Zn-2+ completely inhibited the enzyme activity, while the inhibition by Co-2+ was only partial. Fe-2+ did not exert any effect on the activity. The enzyme activity was completely inhibited by EDTA and was restored almost to the original value by metal ions like Mn-2+, Mg-2+, Ca-2+ and Ba-2+. The approximate molecular weight of the purified enzyme was estimated to be 56 000."} {"id": "PMID:165833", "title": "Collagenase production by Achromobacter iophagus.", "content": "Achromobacter iophagus produced collagenase (EC 3.4.24.3) when cultured aerobically in buffer containing 5% peptone. The bacterium is non-pathogenic and tests on rabbits indicated that the culture medium was atoxic. The collagenase, which hydrolyzed insoluble and soluble native collagen, was purified by (NH4)2 SO4 precipitation, starch block electrophoresis, and gel filtration. It was shown to be serologically distinct from Clostridium histolyticum collagenase and to have molecular weight and sedimentation coefficient values of approx. 112 000 and 5.3 S, respectively.", "contents": "Collagenase production by Achromobacter iophagus. Achromobacter iophagus produced collagenase (EC 3.4.24.3) when cultured aerobically in buffer containing 5% peptone. The bacterium is non-pathogenic and tests on rabbits indicated that the culture medium was atoxic. The collagenase, which hydrolyzed insoluble and soluble native collagen, was purified by (NH4)2 SO4 precipitation, starch block electrophoresis, and gel filtration. It was shown to be serologically distinct from Clostridium histolyticum collagenase and to have molecular weight and sedimentation coefficient values of approx. 112 000 and 5.3 S, respectively."} {"id": "PMID:165834", "title": "Separation of lipoamide dehydrogenase isoenzymes by affinity chromatography.", "content": "1. Lipoamide dehydrogenase NADH: lipoamide oxidoreductase, (EC 1.6.4.3) from pig heart has been separated into two sets of isoenzymes by chromatography on lipoyl- and NAD+-derivatized Sepharose-4B matrices. The first fraction is eluted at 30 mM sodium phosphate buffer (pH 7.2), the other requires a higher ionic strength. The two groups originate from the alpha-ketoglutarate and the pyruvate dehydrogenase complex respectively. 2, Hydrophobic chromatography on a homologous series of alkyl-Sepharoses lead to similar results. The first fraction is eluted with 30 mM phosphate buffer in the case of propyl- and butyl-Sepharose but a high ionic strength is required in the case of an increased chain length (C5--C6). The second fraction is reversibly bound on Sepharose-NC3 and -NC4 but binding becomes irreversible at higher chain lengths. 3. Aminoalkyl-Sepharose behave qualitatively as the alkyl derivatives although elution, particularly in the case of the second fraction, can be realized at lower ionic strength. 4. Matrices which are negatively charged (Sepharose-NCnCOOH, n equal 3--7) have no affinity at pH 7.2. 5. The influence of a neutral polar substituent has been studied by comparing the following matrices: Sepharose-NC6OH, Sepharose-NC6NH2 and Sepharose NC6. Binding of the various isoenzymes is completely reversible in the case of a Sepharose-NC6OH matrix and the elution behaviour is identical to that on propyl- and butyl matrices.", "contents": "Separation of lipoamide dehydrogenase isoenzymes by affinity chromatography. 1. Lipoamide dehydrogenase NADH: lipoamide oxidoreductase, (EC 1.6.4.3) from pig heart has been separated into two sets of isoenzymes by chromatography on lipoyl- and NAD+-derivatized Sepharose-4B matrices. The first fraction is eluted at 30 mM sodium phosphate buffer (pH 7.2), the other requires a higher ionic strength. The two groups originate from the alpha-ketoglutarate and the pyruvate dehydrogenase complex respectively. 2, Hydrophobic chromatography on a homologous series of alkyl-Sepharoses lead to similar results. The first fraction is eluted with 30 mM phosphate buffer in the case of propyl- and butyl-Sepharose but a high ionic strength is required in the case of an increased chain length (C5--C6). The second fraction is reversibly bound on Sepharose-NC3 and -NC4 but binding becomes irreversible at higher chain lengths. 3. Aminoalkyl-Sepharose behave qualitatively as the alkyl derivatives although elution, particularly in the case of the second fraction, can be realized at lower ionic strength. 4. Matrices which are negatively charged (Sepharose-NCnCOOH, n equal 3--7) have no affinity at pH 7.2. 5. The influence of a neutral polar substituent has been studied by comparing the following matrices: Sepharose-NC6OH, Sepharose-NC6NH2 and Sepharose NC6. Binding of the various isoenzymes is completely reversible in the case of a Sepharose-NC6OH matrix and the elution behaviour is identical to that on propyl- and butyl matrices."} {"id": "PMID:165835", "title": "Influence of glucocorticoids on some morphological and biochemical aspects of rat small intestinal mucosa.", "content": "Glucocorticoid administration (5 mg/day per 100 g of body weight) to month-old rats elicited a reduction of maltase and alkaline phosphatase. Corticotrophic stimulation on month-old rats elicited a specific rise in maltase and alkaline phosphatase activities, total protein content remaining unchanged. Immunological, histological, radioautographical and biochemical studies have shown that these two opposing phenomena do not depend on enzyme activation, on membrane stabilisation, or on modifications of proliferative parameters of the intestinal epithelium. They appear rather to derive from the same origin, i.e. the action of glucocorticoids on the enterocyte differentiation.", "contents": "Influence of glucocorticoids on some morphological and biochemical aspects of rat small intestinal mucosa. Glucocorticoid administration (5 mg/day per 100 g of body weight) to month-old rats elicited a reduction of maltase and alkaline phosphatase. Corticotrophic stimulation on month-old rats elicited a specific rise in maltase and alkaline phosphatase activities, total protein content remaining unchanged. Immunological, histological, radioautographical and biochemical studies have shown that these two opposing phenomena do not depend on enzyme activation, on membrane stabilisation, or on modifications of proliferative parameters of the intestinal epithelium. They appear rather to derive from the same origin, i.e. the action of glucocorticoids on the enterocyte differentiation."} {"id": "PMID:165836", "title": "Spectroscopic properties of ferrous heme complexes of sterically hindered ligands.", "content": "Mesoheme IX complexes of sterically hindered ligands 2-methylimidazole, tert-butylamine and 2-methylpyridine in aqueous glycerol solutions are characterized by broad visible absorption spectra at ambient temperature exhibiting close similarities to high-spin ferrous hemeproteins. Spectrophotometric titrations of mesoheme IX with these ligands indicate well-defined equilibria for 2-methylimidazole and tert-butylamine corresponding to the formation of penta-coordinate strong-field ligand complexes. Variable temperature spectra of these complexes from ambient to 77 degrees K exhibit a change to hemochrome spectra characteristic of the low-spin unhindered ligand complexes. Corresponding changes in the visible spectra are not observed for the high-spin hemeproteins deoxymyoglobin, horse-radish peroxidase and cytochrome \u0107. The appropriate utilization of these hindered ligand heme complexes as model systems for high-spin ferrous hemeproteins has been discussed.", "contents": "Spectroscopic properties of ferrous heme complexes of sterically hindered ligands. Mesoheme IX complexes of sterically hindered ligands 2-methylimidazole, tert-butylamine and 2-methylpyridine in aqueous glycerol solutions are characterized by broad visible absorption spectra at ambient temperature exhibiting close similarities to high-spin ferrous hemeproteins. Spectrophotometric titrations of mesoheme IX with these ligands indicate well-defined equilibria for 2-methylimidazole and tert-butylamine corresponding to the formation of penta-coordinate strong-field ligand complexes. Variable temperature spectra of these complexes from ambient to 77 degrees K exhibit a change to hemochrome spectra characteristic of the low-spin unhindered ligand complexes. Corresponding changes in the visible spectra are not observed for the high-spin hemeproteins deoxymyoglobin, horse-radish peroxidase and cytochrome \u0107. The appropriate utilization of these hindered ligand heme complexes as model systems for high-spin ferrous hemeproteins has been discussed."} {"id": "PMID:165837", "title": "Binding of progesterone to the proteins of the uterine luminal fluid. Identification of uteroglobin as the binding protein.", "content": "1. The uterine luminal fluid of rabbits treated with estradiol and progesterone contains a protein factor with high affinity for [3-H] progesterone which is not present in the uterine secretion of control rabbits treated with estradiol. 2. This progesterone dependent factor is shown by gel filtration and polyacrylamide gel electrophoresis to be identical with the uterus specific protein uteroglobin, which seems to be required during the preimplantation phase. Uteroglobin specific antiserum, prepared in guinea pigs, completely inhibits the progesterone binding activity of the proteins of the uterine fluid. 3. Progesterone binding to uteroglobin is dependent upon millimolar concentrations of dithioerythritol. At saturation, one molecule of progesterone binds per uteroglobin molecule and the apparent association constant is 2 x 10-6 M-1 at 0 degrees C. 4. The progesterone binding species of uteroglobin exhibits a molecular weight of around 12 000 on polyacrylamide gels containing dodecylsulfate, and of 15 000 upon gel filtration, indicating a non-globular shape. This molecule is compased of two subunits of similar molecular size which are held together by a disulfide bridge among other forces.", "contents": "Binding of progesterone to the proteins of the uterine luminal fluid. Identification of uteroglobin as the binding protein. 1. The uterine luminal fluid of rabbits treated with estradiol and progesterone contains a protein factor with high affinity for [3-H] progesterone which is not present in the uterine secretion of control rabbits treated with estradiol. 2. This progesterone dependent factor is shown by gel filtration and polyacrylamide gel electrophoresis to be identical with the uterus specific protein uteroglobin, which seems to be required during the preimplantation phase. Uteroglobin specific antiserum, prepared in guinea pigs, completely inhibits the progesterone binding activity of the proteins of the uterine fluid. 3. Progesterone binding to uteroglobin is dependent upon millimolar concentrations of dithioerythritol. At saturation, one molecule of progesterone binds per uteroglobin molecule and the apparent association constant is 2 x 10-6 M-1 at 0 degrees C. 4. The progesterone binding species of uteroglobin exhibits a molecular weight of around 12 000 on polyacrylamide gels containing dodecylsulfate, and of 15 000 upon gel filtration, indicating a non-globular shape. This molecule is compased of two subunits of similar molecular size which are held together by a disulfide bridge among other forces."} {"id": "PMID:165838", "title": "Effect of decapitation and ACTH on somatic development of the rabbit fetus.", "content": "Rabbit fetuses were decapitated, injected with ACTH or decapitated and injected with ACTH on day 24 of gestation. On day 29 the body weight and weight of the interscapular fat pad were compared with those of littermates. The weight, total DNA and weight/DNA ratio of the liver, heart and kidney were measured in experimental and control fetuses. A comparison was made between decapitated and control fetuses of the length of the hind limb bones and number of ossified vertebrae. The body weight of the decapitated or ACTH-injected fetus ranked significantly below the mean for the litter, but decapitated fetuses injected with ACTH ranked close to the litter mean. The growth retardation of the decapitated fetus was not manifest in the kidneys which were heavier and had a greater number of cells than normal, nor in the cell size of the heart, liver or kidneys which were equal to those of the heaviest fetus in the litter. Decapitation had no specific effect on ossification. Growth retardation of the ACTH-injected fetus was mirrored by different patterns of DNA and weight/DNA reduction in the three organs studied. Decapitation retards growth in body weight of the fetal rabbit which may be corrected by ACTH. It is concluded that the hypophyseal-adrenal axis plays a role in the control of normal fetal growth but that excess secretion of glucocorticoids results in stunting.", "contents": "Effect of decapitation and ACTH on somatic development of the rabbit fetus. Rabbit fetuses were decapitated, injected with ACTH or decapitated and injected with ACTH on day 24 of gestation. On day 29 the body weight and weight of the interscapular fat pad were compared with those of littermates. The weight, total DNA and weight/DNA ratio of the liver, heart and kidney were measured in experimental and control fetuses. A comparison was made between decapitated and control fetuses of the length of the hind limb bones and number of ossified vertebrae. The body weight of the decapitated or ACTH-injected fetus ranked significantly below the mean for the litter, but decapitated fetuses injected with ACTH ranked close to the litter mean. The growth retardation of the decapitated fetus was not manifest in the kidneys which were heavier and had a greater number of cells than normal, nor in the cell size of the heart, liver or kidneys which were equal to those of the heaviest fetus in the litter. Decapitation had no specific effect on ossification. Growth retardation of the ACTH-injected fetus was mirrored by different patterns of DNA and weight/DNA reduction in the three organs studied. Decapitation retards growth in body weight of the fetal rabbit which may be corrected by ACTH. It is concluded that the hypophyseal-adrenal axis plays a role in the control of normal fetal growth but that excess secretion of glucocorticoids results in stunting."} {"id": "PMID:165842", "title": "The factors controlling stem cell recirculation. II. ACTH-induced inhibition of migration of hemopoietic stem cells.", "content": "Injections of ACTH of prolonged action (twice 1.5 units per mouse) given to lethally (800 R) irradiated mice with a hind limb shielded to the middle of the tibia brought about a twofold decrease in the number of spleen colonies. ACTH injections after sublethal whole-body irradiation (600 R) did not affect the number of endogenous spleen colonies. ACTH injection of normal mice brought about a substantial decrease in the CFU content in the circulating blood at the time of increased 11-hydroxycorticosteroid concentrations in the plasma. The results obtained are interpreted as inhibition of CFU migration from a shielded area of bone marrow induced by a high 11-hydroxycorticosteroid content in the plasma that followed ACTH injections which had no mitostatic effect on CFU proliferation.", "contents": "The factors controlling stem cell recirculation. II. ACTH-induced inhibition of migration of hemopoietic stem cells. Injections of ACTH of prolonged action (twice 1.5 units per mouse) given to lethally (800 R) irradiated mice with a hind limb shielded to the middle of the tibia brought about a twofold decrease in the number of spleen colonies. ACTH injections after sublethal whole-body irradiation (600 R) did not affect the number of endogenous spleen colonies. ACTH injection of normal mice brought about a substantial decrease in the CFU content in the circulating blood at the time of increased 11-hydroxycorticosteroid concentrations in the plasma. The results obtained are interpreted as inhibition of CFU migration from a shielded area of bone marrow induced by a high 11-hydroxycorticosteroid content in the plasma that followed ACTH injections which had no mitostatic effect on CFU proliferation."} {"id": "PMID:165844", "title": "Noradrenaline and motor transmission in the vas deferens of the mouse.", "content": "1. A comprehensive investigation of the innervation of the vas deferens of the mouse was made using pharmacological, histochemical and electronmicroscopical techniques. 2. Guanethidine inhibited the response of the vas to transmural stimulation and potentiated the response to noradrenaline (NA). Phentolamine abolished responses to NA and to transmural stimulation. 3. After chemical sympathectomy degenerative changes were seen in presumptive noradrenergic axons; histochemical fluorescence due to catecholamines was absent. The vas failed to respond to transmural stimulation, and a 10-fold increase in sensitivity of the vas to exogenous NA was observed. 4. NA is shown to diffuse slowly through this tissue whose muscle cells are densely packed. This is disscussed in relation to the apparent \"insensitivity\" of the vas to exogenous NA. 5. A cholinergic component was identified histochemically which did not contribute significantly to the motor response of the vas as chemical sympathectomy abolished completely the motor response elicited by transmural stimulation. 6. It is concluded that NA is the motor trnasmitter for the smooth muscle of the vas deferens of the mouse.", "contents": "Noradrenaline and motor transmission in the vas deferens of the mouse. 1. A comprehensive investigation of the innervation of the vas deferens of the mouse was made using pharmacological, histochemical and electronmicroscopical techniques. 2. Guanethidine inhibited the response of the vas to transmural stimulation and potentiated the response to noradrenaline (NA). Phentolamine abolished responses to NA and to transmural stimulation. 3. After chemical sympathectomy degenerative changes were seen in presumptive noradrenergic axons; histochemical fluorescence due to catecholamines was absent. The vas failed to respond to transmural stimulation, and a 10-fold increase in sensitivity of the vas to exogenous NA was observed. 4. NA is shown to diffuse slowly through this tissue whose muscle cells are densely packed. This is disscussed in relation to the apparent \"insensitivity\" of the vas to exogenous NA. 5. A cholinergic component was identified histochemically which did not contribute significantly to the motor response of the vas as chemical sympathectomy abolished completely the motor response elicited by transmural stimulation. 6. It is concluded that NA is the motor trnasmitter for the smooth muscle of the vas deferens of the mouse."} {"id": "PMID:165845", "title": "Nicotine-induced stimulation of steroidogenesis in adrenocortical cells of the cat.", "content": "1. The effect of nicotine on steroid production and release from trypsin-dispersed cat adrenocortical cells was investigated. 2. Nicotine, like adrenocorticotrophin (ACTH), elicited a dose-dependent increase in steroidogenesis, which depended upon the presence of calcium in the medium. 3. Augmented steroid production evoked by submaximal concentrations of ACTH monobutyryl cyclic adenosine 3',5'-monophosphate (AMP), or prostaglandin E2 was further enhanced by steroidogenic concentrations of nicotine. 4. These results are discussed in relation to the possible mode of action of nicotine on cortical cells and to the potential consequences of smoking during stress.", "contents": "Nicotine-induced stimulation of steroidogenesis in adrenocortical cells of the cat. 1. The effect of nicotine on steroid production and release from trypsin-dispersed cat adrenocortical cells was investigated. 2. Nicotine, like adrenocorticotrophin (ACTH), elicited a dose-dependent increase in steroidogenesis, which depended upon the presence of calcium in the medium. 3. Augmented steroid production evoked by submaximal concentrations of ACTH monobutyryl cyclic adenosine 3',5'-monophosphate (AMP), or prostaglandin E2 was further enhanced by steroidogenic concentrations of nicotine. 4. These results are discussed in relation to the possible mode of action of nicotine on cortical cells and to the potential consequences of smoking during stress."} {"id": "PMID:165846", "title": "Role of cyclic adenosine 3',5'-monophosphate in the isoprenaline-induced relaxation of the oestrogen dominated rabbit uterus.", "content": "1. The role of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated. 2. Isoprenaline 2 times 10- minus 8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 times 10- minus 6 M produced both inhibition of mechanical activity and increase in cyclic AMP. 3. The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 X 10-MINUS 6 M. 4. Dibutyryl-ccylic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones. 5. It is concluded that cyclic AMP may be a mediator of the beta-adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of beta-adrenoceptors and relaxation. Other mechanisms may also exist.", "contents": "Role of cyclic adenosine 3',5'-monophosphate in the isoprenaline-induced relaxation of the oestrogen dominated rabbit uterus. 1. The role of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated. 2. Isoprenaline 2 times 10- minus 8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 times 10- minus 6 M produced both inhibition of mechanical activity and increase in cyclic AMP. 3. The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 X 10-MINUS 6 M. 4. Dibutyryl-ccylic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones. 5. It is concluded that cyclic AMP may be a mediator of the beta-adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of beta-adrenoceptors and relaxation. Other mechanisms may also exist."} {"id": "PMID:165847", "title": "Tetramethylenedisulphotetramine: an inhibitor of gamma-aminobutyric acid induced depolarization of the isolated superior cervical ganglion of the rat.", "content": "Tetramethylenedisulphotetramine (TETS), a potent convulsant, antagonized the depolarizing action gamma-aminobutyric acid (GABA) in the isolated superior cervical ganglion of the rat. No antagonism of responses to the cholinomimetic agent carbachol was observed. TETS appeared to act in a non-competitive manner and was reversible. Its activity profile was comparable to that of bicuculline in the same tissue except that the latter appears to act in a competitive manner.", "contents": "Tetramethylenedisulphotetramine: an inhibitor of gamma-aminobutyric acid induced depolarization of the isolated superior cervical ganglion of the rat. Tetramethylenedisulphotetramine (TETS), a potent convulsant, antagonized the depolarizing action gamma-aminobutyric acid (GABA) in the isolated superior cervical ganglion of the rat. No antagonism of responses to the cholinomimetic agent carbachol was observed. TETS appeared to act in a non-competitive manner and was reversible. Its activity profile was comparable to that of bicuculline in the same tissue except that the latter appears to act in a competitive manner."} {"id": "PMID:165850", "title": "Colours experienced in dreams.", "content": "Colours seen in dreams by six observers were recorded from memory and plotted on a CIE u, v, chromaticity diagram. Only about half the dreams recorded contained colour, and in those in which colour appeared the more saturated purples, blues and blue greens were absent. It is suggested that during achromatic dreams the areas of the visual cortex which seem to respond only to colour may be inoperative. The paucity of blue in dreams could be anatomically related to the small population of blue units in the colour areas of the cortex.", "contents": "Colours experienced in dreams. Colours seen in dreams by six observers were recorded from memory and plotted on a CIE u, v, chromaticity diagram. Only about half the dreams recorded contained colour, and in those in which colour appeared the more saturated purples, blues and blue greens were absent. It is suggested that during achromatic dreams the areas of the visual cortex which seem to respond only to colour may be inoperative. The paucity of blue in dreams could be anatomically related to the small population of blue units in the colour areas of the cortex."} {"id": "PMID:165851", "title": "Carcinoma of the large bowel in the Sudan.", "content": "Large bowel cancer is not common but is showing increased frequency in the northern part of the Sudan. It is relatively uncommon among southerners, which may be due to the socio-economic factors prevailing in the Sudan. The disease affected our population at a younger age than has been generally reported in the literature, and the lesions in nearly 30 per cent were of the mucoid and undifferentiated types. The incidence in young adults is difficult to explain in the absence of precancerous lesions, and there is not enough evidence to incriminate parasitic infestation.", "contents": "Carcinoma of the large bowel in the Sudan. Large bowel cancer is not common but is showing increased frequency in the northern part of the Sudan. It is relatively uncommon among southerners, which may be due to the socio-economic factors prevailing in the Sudan. The disease affected our population at a younger age than has been generally reported in the literature, and the lesions in nearly 30 per cent were of the mucoid and undifferentiated types. The incidence in young adults is difficult to explain in the absence of precancerous lesions, and there is not enough evidence to incriminate parasitic infestation."} {"id": "PMID:165852", "title": "Possible parathyroid origin of gastrin in a patient with multiple endocrine adenopathy type I.", "content": "After removal of two large pancreactic insulinomas, although the presenting spontaneous hypoglycaemia was eliminated, severe and persisting haematemesis and melaena supervened with a rise in serum gastrin. The patient had multiple endocrine adenopathy (pituitary, parathyroids and islet cells), but no evidence of a pancreatic gastrin-producing tumour. After emergency gastric operation for the bleeding, the serum gastrin remained high until the hypercalcaemia and hyperparathyroidism had been corrected by subtotal parathyroidectomy. Immunofluorescence studies showed gastrin in the parathyroid tissue.", "contents": "Possible parathyroid origin of gastrin in a patient with multiple endocrine adenopathy type I. After removal of two large pancreactic insulinomas, although the presenting spontaneous hypoglycaemia was eliminated, severe and persisting haematemesis and melaena supervened with a rise in serum gastrin. The patient had multiple endocrine adenopathy (pituitary, parathyroids and islet cells), but no evidence of a pancreatic gastrin-producing tumour. After emergency gastric operation for the bleeding, the serum gastrin remained high until the hypercalcaemia and hyperparathyroidism had been corrected by subtotal parathyroidectomy. Immunofluorescence studies showed gastrin in the parathyroid tissue."} {"id": "PMID:165853", "title": "Neuropathy in latent hereditary hepatic porphyria.", "content": "Peripheral nerve conduction velocoties were measured in 20 patients with acute intermittent porphyria and five with variegate porphyria and in 25 controls matched for age and sex. None of the porphyric patients had acute symptoms on examination, and nine had never had symptoms. Compared with the controls, patients had a significantly slower conduction velocity of the slower motor fibres of the ulnar nerve (P less than 0-001) and a slower sensory conduction velocity of the ulnar and median nerves (P less than 0-05). There was no significant difference between the patients and controls in the maximum motor conductionvelocity of the median, ulnar, deep peroneal, or posterior tibial nerves. Slight peripheral neuropathy seems to be associated with latent hereditary hepatic porphyria, even in patients who have never had symptoms.", "contents": "Neuropathy in latent hereditary hepatic porphyria. Peripheral nerve conduction velocoties were measured in 20 patients with acute intermittent porphyria and five with variegate porphyria and in 25 controls matched for age and sex. None of the porphyric patients had acute symptoms on examination, and nine had never had symptoms. Compared with the controls, patients had a significantly slower conduction velocity of the slower motor fibres of the ulnar nerve (P less than 0-001) and a slower sensory conduction velocity of the ulnar and median nerves (P less than 0-05). There was no significant difference between the patients and controls in the maximum motor conductionvelocity of the median, ulnar, deep peroneal, or posterior tibial nerves. Slight peripheral neuropathy seems to be associated with latent hereditary hepatic porphyria, even in patients who have never had symptoms."} {"id": "PMID:165854", "title": "Methodichlorophen as anti-tumor drug.", "content": "Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.", "contents": "Methodichlorophen as anti-tumor drug. Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken."} {"id": "PMID:165855", "title": "Peripheral neuropathy and indomethacin.", "content": "A patient with seronegative inflammatory polyarthritis developed a predominantly motorperipheral neuropathy associated with the use of indomethacin. Three other cases of peripheral neuropathy associated with indomethacin treatment have been reported to the Committee on Safety of Medicines. In all cases the neuropathy regressed when indomethacinwas stopped. Peripheral neuropathy should be recognized as a rare complication of indomethacin therapy and considered in the differential diagnosis of a neuropathy accompanyingrheumatoid arthritis.", "contents": "Peripheral neuropathy and indomethacin. A patient with seronegative inflammatory polyarthritis developed a predominantly motorperipheral neuropathy associated with the use of indomethacin. Three other cases of peripheral neuropathy associated with indomethacin treatment have been reported to the Committee on Safety of Medicines. In all cases the neuropathy regressed when indomethacinwas stopped. Peripheral neuropathy should be recognized as a rare complication of indomethacin therapy and considered in the differential diagnosis of a neuropathy accompanyingrheumatoid arthritis."} {"id": "PMID:165857", "title": "Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia.", "content": "In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia.", "contents": "Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia. In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia."} {"id": "PMID:165860", "title": "Value of Papanicolaou-stained smears in the diagnosis of trichomoniasis, candidiasis, and cervical herpes simplex virus infection in women.", "content": "In the diagnosis of trichomoniasis Papanicolaou-stained cervical smears gave marginally better results than cultures of vaginal secretion; stained cervical smears and wet films of vaginal material gave similar results. Culture of vaginal secretion on Sabouraud's medium gave the best results in the diagnosis of candidiasis; Papanicolaou-stained smears gave significantly fewer positive results than either cultures or Gram-stained vaginal smears. Papanicolaou-stained smears were reported as positive in only two of five patients with cervical herpes simplex virus infection. It is concluded that Papanicolaou smears are as good as wet films or cultures in the diagnosis of trichomoniasis but cannot be relied on for the diagnosis of candidiasis, or for detecting herpes simplex virus infection.", "contents": "Value of Papanicolaou-stained smears in the diagnosis of trichomoniasis, candidiasis, and cervical herpes simplex virus infection in women. In the diagnosis of trichomoniasis Papanicolaou-stained cervical smears gave marginally better results than cultures of vaginal secretion; stained cervical smears and wet films of vaginal material gave similar results. Culture of vaginal secretion on Sabouraud's medium gave the best results in the diagnosis of candidiasis; Papanicolaou-stained smears gave significantly fewer positive results than either cultures or Gram-stained vaginal smears. Papanicolaou-stained smears were reported as positive in only two of five patients with cervical herpes simplex virus infection. It is concluded that Papanicolaou smears are as good as wet films or cultures in the diagnosis of trichomoniasis but cannot be relied on for the diagnosis of candidiasis, or for detecting herpes simplex virus infection."} {"id": "PMID:165861", "title": "Genital yeasts in female patients attending a VD clinic.", "content": "A study of 552 female patients was undertaken to determine the frequency of yeast infections in women attending a V.D. clinic. The findings were as follows: (1) 207 of the 552 (37.5 per cent.) were found to have yeasts. (2) C. albicans accounted for 86 per cent. of these yeasts. (3) There was no difference in incidence related to age or seasonal variation. (4) Oral contraceptives increased the incidence of yeasts (43.2 per cent. on \"the pill\"; 33.2 per cent. not on the pill\"), but the incidence of Trichomonas was decreased (6.8 per cent. on \"the pill\", 19.3 per cent. not on \"the pill\"). (5) Previous antibiotics also contributed to the incidence; 23.2 per cent. of patients with yeasts had had antibiotics previously compared with 13.6 per cent. of those without yeasts. (6) Other infections were associated in seventy cases (33.8 per cent.). (7) Culture is essential for the detection of yeasts; 64 per cent. were positive only on culture. (8) Symptoms were present in 70 per cent. of patients with yeasts. (9) 93 male consorts were seen and in 31 (33 per cent.) yeasts were detected by smear, or culture. Of the 47 in whom cultures were examined, 23 (49 per cent.) were positive. The general factors affecting the incidence of yeasts are discussed as well as the differentiation of the saprophytic from the pathogenic role of yeasts. It is suggested that asymptomatic yeast infections are often best treated, but that each case should be considered individually. Male consorts should also be treated to prevent re-infection.", "contents": "Genital yeasts in female patients attending a VD clinic. A study of 552 female patients was undertaken to determine the frequency of yeast infections in women attending a V.D. clinic. The findings were as follows: (1) 207 of the 552 (37.5 per cent.) were found to have yeasts. (2) C. albicans accounted for 86 per cent. of these yeasts. (3) There was no difference in incidence related to age or seasonal variation. (4) Oral contraceptives increased the incidence of yeasts (43.2 per cent. on \"the pill\"; 33.2 per cent. not on the pill\"), but the incidence of Trichomonas was decreased (6.8 per cent. on \"the pill\", 19.3 per cent. not on \"the pill\"). (5) Previous antibiotics also contributed to the incidence; 23.2 per cent. of patients with yeasts had had antibiotics previously compared with 13.6 per cent. of those without yeasts. (6) Other infections were associated in seventy cases (33.8 per cent.). (7) Culture is essential for the detection of yeasts; 64 per cent. were positive only on culture. (8) Symptoms were present in 70 per cent. of patients with yeasts. (9) 93 male consorts were seen and in 31 (33 per cent.) yeasts were detected by smear, or culture. Of the 47 in whom cultures were examined, 23 (49 per cent.) were positive. The general factors affecting the incidence of yeasts are discussed as well as the differentiation of the saprophytic from the pathogenic role of yeasts. It is suggested that asymptomatic yeast infections are often best treated, but that each case should be considered individually. Male consorts should also be treated to prevent re-infection."} {"id": "PMID:165862", "title": "Neutral red with photoinactivation in the treatment of herpes genitalis.", "content": "A clinical trial was undertaken to compare the efficacy of neutral red photodynamic inactivation treatment of genital herpes infections with that of a non-photoactive dye, phenol red, as a control. In a series of nineteen patients with virologically proven herpes genitalis who were adequately followed, eleven were treated with neutral red, and eight with phenol red; no difference in response to therapy was found between the two groups, and it is concluded that under the conditions of this trial neutral red with photoinactivation was not effective in the treatment of acute genital herpes infections. Approximately 75 per cent. of those with vulval lesions also had concurrent cervical infection, so that an effective topical treatment would need to be applicable to both anatomical sites.", "contents": "Neutral red with photoinactivation in the treatment of herpes genitalis. A clinical trial was undertaken to compare the efficacy of neutral red photodynamic inactivation treatment of genital herpes infections with that of a non-photoactive dye, phenol red, as a control. In a series of nineteen patients with virologically proven herpes genitalis who were adequately followed, eleven were treated with neutral red, and eight with phenol red; no difference in response to therapy was found between the two groups, and it is concluded that under the conditions of this trial neutral red with photoinactivation was not effective in the treatment of acute genital herpes infections. Approximately 75 per cent. of those with vulval lesions also had concurrent cervical infection, so that an effective topical treatment would need to be applicable to both anatomical sites."} {"id": "PMID:165863", "title": "Donovanosis (granuloma inguinale) of the oral cavity.", "content": "A female patient suffering from donovanosis of the oral cavity without associated lesions elsewhere is reported. The importance of remembering donovanosis in the differential diagnosis of chronic granulomatous ulceration of the mouth is emphasized.", "contents": "Donovanosis (granuloma inguinale) of the oral cavity. A female patient suffering from donovanosis of the oral cavity without associated lesions elsewhere is reported. The importance of remembering donovanosis in the differential diagnosis of chronic granulomatous ulceration of the mouth is emphasized."} {"id": "PMID:165867", "title": "Effect of withdrawal from chronic ethanol ingestion on the cAMP response of cerebral cortical slices using the agonists histamine, serotonin, and other neurotransmitters.", "content": "The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and gamma-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by alpha- and beta-adrenergic antagonists, possibly because of the nonspecific membrane stablizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.", "contents": "Effect of withdrawal from chronic ethanol ingestion on the cAMP response of cerebral cortical slices using the agonists histamine, serotonin, and other neurotransmitters. The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and gamma-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by alpha- and beta-adrenergic antagonists, possibly because of the nonspecific membrane stablizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed."} {"id": "PMID:165868", "title": "Presynaptic effect of the aziridinium ion of acetylcholine mustard (methyl-2-acetoxyethyl-2'-chloroethylamine) on the phrenic nerve--rat diaphragm preparation.", "content": "The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca-2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported date for toxicity of acetylcholine mustard aziridinium ion in the mouse.", "contents": "Presynaptic effect of the aziridinium ion of acetylcholine mustard (methyl-2-acetoxyethyl-2'-chloroethylamine) on the phrenic nerve--rat diaphragm preparation. The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca-2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported date for toxicity of acetylcholine mustard aziridinium ion in the mouse."} {"id": "PMID:165869", "title": "Cellular hypersensitivity to basic myelin (P2) protein in the Guillain-Barr\u00e9 syndrome.", "content": "Lymphocytes of 29 subjects were assayed for MIF production in response to P2 peripheral nerve protein, crude human peripheral nerve and human central nervous system Al basic myelin protein. Seven were performed in normal control subjects, 12 in Guillain-Barre patients (GB), 5 with other polyneuropathies and 5 in patients with multiple sclerosis (MS). Only GB patients with acute illness produced MIF in response to neuritogenic P2 protein and crude human nerve. Two MS patients in the acute phase of an exacerbation and one GB patient produced MIF in Response to Al protein. The results of this study demonstrate cellular hypersensitivity to a neuritogenic consituent in peripheral nervous tissue and support the concept that this may be important in the pathogenesis of GB.", "contents": "Cellular hypersensitivity to basic myelin (P2) protein in the Guillain-Barr\u00e9 syndrome. Lymphocytes of 29 subjects were assayed for MIF production in response to P2 peripheral nerve protein, crude human peripheral nerve and human central nervous system Al basic myelin protein. Seven were performed in normal control subjects, 12 in Guillain-Barre patients (GB), 5 with other polyneuropathies and 5 in patients with multiple sclerosis (MS). Only GB patients with acute illness produced MIF in response to neuritogenic P2 protein and crude human nerve. Two MS patients in the acute phase of an exacerbation and one GB patient produced MIF in Response to Al protein. The results of this study demonstrate cellular hypersensitivity to a neuritogenic consituent in peripheral nervous tissue and support the concept that this may be important in the pathogenesis of GB."} {"id": "PMID:165870", "title": "Neurophysiological changes following spinal cord lesions in man.", "content": "A study has been made of the neurophysiological changes that follow spinal cord lesions in man. The Achilles tendon reflex (ATR) is used to estimate transmission in the Ia monosynaptic pathway, and the tonic vibration reflex (TVR) to estimate transmission in the Ia polysynaptic pathway to motoneurons. The inhibition of the H reflex by vibration is used as an estimate of presynaptic inhibition of the Ia monosynaptic pathway. Immediately following a complete lesion of the spinal cord presynaptic inhibition of the Ia monosynaptic pathway appears to be greatly increased. This enhanced inihibition may last several months but it eventually declines and in some instances becomes less than normal. Transmission in the Ia polysynaptic pathway is permanently abolished by a complete spinal lesion. A hypothesis is developed from these findings to explain the evolution of some of the clinical features that follow complete spinal lesions in man. Distinct differences are observed when the spinal lesion is incomplete. Transmission in the Ia polysynaptic pathway may be preserved and there may be no increase in presynaptic inhibition. These differences may depend upon the integrity of certain spinal long tracts which cannot be tested clinically.", "contents": "Neurophysiological changes following spinal cord lesions in man. A study has been made of the neurophysiological changes that follow spinal cord lesions in man. The Achilles tendon reflex (ATR) is used to estimate transmission in the Ia monosynaptic pathway, and the tonic vibration reflex (TVR) to estimate transmission in the Ia polysynaptic pathway to motoneurons. The inhibition of the H reflex by vibration is used as an estimate of presynaptic inhibition of the Ia monosynaptic pathway. Immediately following a complete lesion of the spinal cord presynaptic inhibition of the Ia monosynaptic pathway appears to be greatly increased. This enhanced inihibition may last several months but it eventually declines and in some instances becomes less than normal. Transmission in the Ia polysynaptic pathway is permanently abolished by a complete spinal lesion. A hypothesis is developed from these findings to explain the evolution of some of the clinical features that follow complete spinal lesions in man. Distinct differences are observed when the spinal lesion is incomplete. Transmission in the Ia polysynaptic pathway may be preserved and there may be no increase in presynaptic inhibition. These differences may depend upon the integrity of certain spinal long tracts which cannot be tested clinically."} {"id": "PMID:165876", "title": "Nucleolar phosphoproteins of normal rat liver and Novikoff hepatoma ascites cells.", "content": "The nucleolar acid-soluble proteins from normal rat liver and Novikoff hepatoma ascites cells were labeled in vivo for 2 hr after the injection of [32P]orthophosphate and in vitro with [gamma-32P]adenosine triphosphate in systems containing 0.25 M sucrose, 5 mM MgCl2, 12.5 mM NaCl, and 0.05 M Tris-HCl buffer, pH 7.3, AT 37 DEGREES. Two-dimensional polyacrylamide gel electrophoresis and autoradiography showed that approximately 40 and 20 protein spots were labeled in vivo and in vitro, respectively. There were some marked differences in labeling in vivo between normal rat liver and Novikoff hepatoma acid-soluble nucleolar proteins. By 32P analysis of gel slices, the proportion of the total 32P incorporated into protein Spot A1-4 was greater in normal liver, and the proportion of 32P incorporated into some high-molecular-weight protein spots, such C23-24 and C26-27, was greater in the Novikoff hepatoma ascites cells. With the in vitro incubation system, the 32P uptake per mg protein was about twice as high in Novikoff hepatoma nucleolar proteins as in normal rat liver nucleolar proteins but, generally, the same proteins were labeled in both tissues.", "contents": "Nucleolar phosphoproteins of normal rat liver and Novikoff hepatoma ascites cells. The nucleolar acid-soluble proteins from normal rat liver and Novikoff hepatoma ascites cells were labeled in vivo for 2 hr after the injection of [32P]orthophosphate and in vitro with [gamma-32P]adenosine triphosphate in systems containing 0.25 M sucrose, 5 mM MgCl2, 12.5 mM NaCl, and 0.05 M Tris-HCl buffer, pH 7.3, AT 37 DEGREES. Two-dimensional polyacrylamide gel electrophoresis and autoradiography showed that approximately 40 and 20 protein spots were labeled in vivo and in vitro, respectively. There were some marked differences in labeling in vivo between normal rat liver and Novikoff hepatoma acid-soluble nucleolar proteins. By 32P analysis of gel slices, the proportion of the total 32P incorporated into protein Spot A1-4 was greater in normal liver, and the proportion of 32P incorporated into some high-molecular-weight protein spots, such C23-24 and C26-27, was greater in the Novikoff hepatoma ascites cells. With the in vitro incubation system, the 32P uptake per mg protein was about twice as high in Novikoff hepatoma nucleolar proteins as in normal rat liver nucleolar proteins but, generally, the same proteins were labeled in both tissues."} {"id": "PMID:165877", "title": "Sulfhydryl group quantitation of hepatoma and liver microsomal fractions.", "content": "The relationship of sulfhydryl and disulfide groups to protein synthesis in normal and rapidly growing tissues was investigated by quantitation of sulfhydryl groups in endoplasmic reticulum and polyribosomes of normal liver and hepatomas. Stripping by ethylenediaminetetraacetate and potassium chloride of normal liver smooth and rough endoplasmic reticulum reduced by 15 percent and increased 30 percent, respectively, the sulfhydryl groups available for carboxamidemethylation by iodoacetamide. This could reflect the removal of ribosomes from rough endoplasmic reticulum with the subsequent exposure of sulfhydryl groups. Exposed sulfhydryl groups of normal mature female rat liver smooth endoplasmic reticulum were decreased to a similar degree by the stripping procedure with ethylenediaminetetra-acetate and potassium chloride when quantitated by either iodoacetamide or 4,4'-dithiodipyridine. This was not the case in young male and female rats, where the stripping procedure failed to decrease the exposed sulfhydryl groups of smooth endoplasmic reticulum. An increase in the quantity of exposed sulfhydryl groups of normal young and mature rat liver rough endoplasmic reticulum after stripping by ethylenediaminetetraacetate and potassium chloride was observed with iodoacetamide. However, when 4,4'-dithiodipyridine was used, no change could be detected. The hypothesis that smooth endoplasmic reticulum arises by degranulation of the rough endoplasmic reticulum in vivo is not supported by our sulfhydryl group quantitation of smooth endoplasmic reticulum and in vitro degranulated rough endoplasmic reticulum. A negative correlation between exposed sulfhydryl groups on the polyribosomes and the rate of growth of normal liver and of Morris hepatomas 6 and 38B suggests that the conformation of the free polyribosomal proteins could be a control factor for the rate of protein synthesis. Faster growing hepatomas also have greater quantities of sulfhydryls and disulfides.", "contents": "Sulfhydryl group quantitation of hepatoma and liver microsomal fractions. The relationship of sulfhydryl and disulfide groups to protein synthesis in normal and rapidly growing tissues was investigated by quantitation of sulfhydryl groups in endoplasmic reticulum and polyribosomes of normal liver and hepatomas. Stripping by ethylenediaminetetraacetate and potassium chloride of normal liver smooth and rough endoplasmic reticulum reduced by 15 percent and increased 30 percent, respectively, the sulfhydryl groups available for carboxamidemethylation by iodoacetamide. This could reflect the removal of ribosomes from rough endoplasmic reticulum with the subsequent exposure of sulfhydryl groups. Exposed sulfhydryl groups of normal mature female rat liver smooth endoplasmic reticulum were decreased to a similar degree by the stripping procedure with ethylenediaminetetra-acetate and potassium chloride when quantitated by either iodoacetamide or 4,4'-dithiodipyridine. This was not the case in young male and female rats, where the stripping procedure failed to decrease the exposed sulfhydryl groups of smooth endoplasmic reticulum. An increase in the quantity of exposed sulfhydryl groups of normal young and mature rat liver rough endoplasmic reticulum after stripping by ethylenediaminetetraacetate and potassium chloride was observed with iodoacetamide. However, when 4,4'-dithiodipyridine was used, no change could be detected. The hypothesis that smooth endoplasmic reticulum arises by degranulation of the rough endoplasmic reticulum in vivo is not supported by our sulfhydryl group quantitation of smooth endoplasmic reticulum and in vitro degranulated rough endoplasmic reticulum. A negative correlation between exposed sulfhydryl groups on the polyribosomes and the rate of growth of normal liver and of Morris hepatomas 6 and 38B suggests that the conformation of the free polyribosomal proteins could be a control factor for the rate of protein synthesis. Faster growing hepatomas also have greater quantities of sulfhydryls and disulfides."} {"id": "PMID:165878", "title": "Regulation of growth of mouse mastocytoma cells.", "content": "N6,O2'-Dibutyryladenosine cyclic 3',5'-phosphate plus theophylline inhibited the growth of the mouse mast cell tumor line PY 815 both in vivo and in vitro. The inhibitory effect on growth in vitro was rapidly reversed following removal of the drugs. Growth inhibition was accompanied by reduced cell surface activity and increased cell-cell adhesion. The drug-treated cells accumulated distinct membrane-bound granules, which are characteristic of more mature mast cells. Treated cells also developed increased amounts of surface-associated acidic mucopolysaccharides. These results suggest that increased intracellular cyclic adenosine 3':5'-monophosphate causes mouse mastocytoma cells to decrease growth and elicits the expression of a more differentiated mast cell phenotype. The effect of the antileukemia drug, 4'-(9-acridinylamino)methanesulfon-m-anisidine, on cyclic adenosine 3':5'-monophosphate and adenosine 5'-triphosphate in mastocytoma cells is also reported.", "contents": "Regulation of growth of mouse mastocytoma cells. N6,O2'-Dibutyryladenosine cyclic 3',5'-phosphate plus theophylline inhibited the growth of the mouse mast cell tumor line PY 815 both in vivo and in vitro. The inhibitory effect on growth in vitro was rapidly reversed following removal of the drugs. Growth inhibition was accompanied by reduced cell surface activity and increased cell-cell adhesion. The drug-treated cells accumulated distinct membrane-bound granules, which are characteristic of more mature mast cells. Treated cells also developed increased amounts of surface-associated acidic mucopolysaccharides. These results suggest that increased intracellular cyclic adenosine 3':5'-monophosphate causes mouse mastocytoma cells to decrease growth and elicits the expression of a more differentiated mast cell phenotype. The effect of the antileukemia drug, 4'-(9-acridinylamino)methanesulfon-m-anisidine, on cyclic adenosine 3':5'-monophosphate and adenosine 5'-triphosphate in mastocytoma cells is also reported."} {"id": "PMID:165879", "title": "Independence of sialic acid levels in normal and malignant growth.", "content": "Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.", "contents": "Independence of sialic acid levels in normal and malignant growth. Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue."} {"id": "PMID:165880", "title": "Transcription of the repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture.", "content": "RNA-DNA saturation hybridization experiments were used to estimate the extent of transcription of repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. Measurements were made with RNA from nontransformed cells in both the subconfluent and confluent stages of growth, transformed cells in normal growth medium, and transformed cells grown in medium containing 5-bromodeoxyuridine, 3 mu-g/ml, a treatment which reduces their tumorigenic potential. No differences were observed in the amount of repetitive DNA transcribed or in the families of sequences expressed, except in transformed cells grown in the presence of 5-bromodeoxyuridine, in which case the extent of transcription was reduced.", "contents": "Transcription of the repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. RNA-DNA saturation hybridization experiments were used to estimate the extent of transcription of repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. Measurements were made with RNA from nontransformed cells in both the subconfluent and confluent stages of growth, transformed cells in normal growth medium, and transformed cells grown in medium containing 5-bromodeoxyuridine, 3 mu-g/ml, a treatment which reduces their tumorigenic potential. No differences were observed in the amount of repetitive DNA transcribed or in the families of sequences expressed, except in transformed cells grown in the presence of 5-bromodeoxyuridine, in which case the extent of transcription was reduced."} {"id": "PMID:165881", "title": "Neoplastic response of the avian liver to host infection with strain Mc29 leukosis verus.", "content": "Studies were made on the oncogenic response of 3086 young chicks to i.v. inoculation of MC29 avian leukosis virus from blood plasma of previous-passage birds or the supernatant fluid of cultures of chick embryo cells infected with strain MC29. Among the large variety of neoplasms of other tissues previously described, there occurred a high incidence of primary growths of the liver. Pathomorphology of the growths frequently differed greatly in both different hosts and the same bird, but some uniformity of the types of neoplasms was evident in many animals. Despite much variation in histopathology, the large proportion of growths could be grouped in several distinctive categories. Examinations by light and electron microscopy provided evidence of derivation of the tumors by alteration of hepatocytes originating principally in the portal regions as indicated by forms transitional from the parenchymal cells to the cells of the different types of growths. Neoplastic aspects of the growths were evident by infiltration and invasion of adjacent tissues, penetration of blood vessels, transplantability to other avian hosts (described in another report), and metastasis to distant organs including the lung, kidney, and spleen. There was no evidence of tumors arising from the biliary system, and growths of cells resembling the biliary type could be traced to altered hepatocytes. None of the findings suggested conversion of biliary-type cells to hepatocytes. Continued growth resulted in anaplastic and metaplastic changes in cell morphology and structural organization and in the formation of cartilage, osteoid, and sarcoma-like spindle-cell tumors of probable epithelial origin. Development of the growths wasnot associated with cirrhosis, and necrosis was limited to infrequent disseminated, essentially unicellular changes or necrobiosis of small groups of cells. The marked variations in the type of virus-induced growths demonstrated the remarkable capacity of cells morphologically inidistinguishable from the hepatocytes for the most diverse alterations in cell structure and tissue organization. This neoplastic response of hepatocytes to the MC29 strain constitutes the only demonstration thus far of the specific hepatocarcinogenic activity of an avian tumor virus.", "contents": "Neoplastic response of the avian liver to host infection with strain Mc29 leukosis verus. Studies were made on the oncogenic response of 3086 young chicks to i.v. inoculation of MC29 avian leukosis virus from blood plasma of previous-passage birds or the supernatant fluid of cultures of chick embryo cells infected with strain MC29. Among the large variety of neoplasms of other tissues previously described, there occurred a high incidence of primary growths of the liver. Pathomorphology of the growths frequently differed greatly in both different hosts and the same bird, but some uniformity of the types of neoplasms was evident in many animals. Despite much variation in histopathology, the large proportion of growths could be grouped in several distinctive categories. Examinations by light and electron microscopy provided evidence of derivation of the tumors by alteration of hepatocytes originating principally in the portal regions as indicated by forms transitional from the parenchymal cells to the cells of the different types of growths. Neoplastic aspects of the growths were evident by infiltration and invasion of adjacent tissues, penetration of blood vessels, transplantability to other avian hosts (described in another report), and metastasis to distant organs including the lung, kidney, and spleen. There was no evidence of tumors arising from the biliary system, and growths of cells resembling the biliary type could be traced to altered hepatocytes. None of the findings suggested conversion of biliary-type cells to hepatocytes. Continued growth resulted in anaplastic and metaplastic changes in cell morphology and structural organization and in the formation of cartilage, osteoid, and sarcoma-like spindle-cell tumors of probable epithelial origin. Development of the growths wasnot associated with cirrhosis, and necrosis was limited to infrequent disseminated, essentially unicellular changes or necrobiosis of small groups of cells. The marked variations in the type of virus-induced growths demonstrated the remarkable capacity of cells morphologically inidistinguishable from the hepatocytes for the most diverse alterations in cell structure and tissue organization. This neoplastic response of hepatocytes to the MC29 strain constitutes the only demonstration thus far of the specific hepatocarcinogenic activity of an avian tumor virus."} {"id": "PMID:165882", "title": "Alteration of hepatocytes by subcarcinogenic exposure to n-2-fluorenylacetamide.", "content": "These experiments examined the effects of a single, subcarcinogenic dose of dimethylnitrosamine or N-hydroxyfluorenylacetamide when administered after a subcarcinogenic dietary regimen of N-2-fluorenylacetamide. Control rats that received either carcinogen diet alone or a single dose of carcinogen demonstrated neither hepatic nodules nor hepatocellular carcinomas. Those animals that received dimethylnitrosamine subsequent to carcinogen diet demonstrated many persistent hepatic nodules and 100% hepato-cellular carcinomas. These data support the concept that the nodules produced by subcarcinogenic ingestion of N-2-fluorenylacetamide are not composed simply of normal hepatocytes undergoing compensatory regeneration but consist of cells that have been altered by the carcinogen. One manifestation of this alteration is an increased susceptibility to further carcinogenic evolution.", "contents": "Alteration of hepatocytes by subcarcinogenic exposure to n-2-fluorenylacetamide. These experiments examined the effects of a single, subcarcinogenic dose of dimethylnitrosamine or N-hydroxyfluorenylacetamide when administered after a subcarcinogenic dietary regimen of N-2-fluorenylacetamide. Control rats that received either carcinogen diet alone or a single dose of carcinogen demonstrated neither hepatic nodules nor hepatocellular carcinomas. Those animals that received dimethylnitrosamine subsequent to carcinogen diet demonstrated many persistent hepatic nodules and 100% hepato-cellular carcinomas. These data support the concept that the nodules produced by subcarcinogenic ingestion of N-2-fluorenylacetamide are not composed simply of normal hepatocytes undergoing compensatory regeneration but consist of cells that have been altered by the carcinogen. One manifestation of this alteration is an increased susceptibility to further carcinogenic evolution."} {"id": "PMID:165883", "title": "The steroid alcohol and estrogen sulfotransferases in rodent and human mammary tumors.", "content": "Rodent and human mammary tumor systems were investigated to relate the steroid alcohol and estrogen sulfotransferase activities to the hormoanl dependency of the tumor as determined by estrogen receptor content. Unlike the normal mammary gland or the hyperplastic alveolar nodule, rodent mammary neoplasms displayed significant levels of these two sulfotransferases. In the hormone-independent mouse tumors produced from out-growth lines D1, D2, and D8, high dehydroepiandrosterone sulfotransferase activity was characteristic of the rapidity with which hyperplastic alveolar nodules developed into a neoplasms (V-max = 52.8 versus 1.8 fmoles/min/mg protein) while estrone sulfotransferase activity was either not detectable or low (V-max = 5.5 fmoles). After oophorectomy of mice bearing slowly developing tumors, both sulfotransferases in the nonregressing neoplasms showed marked increases in activity (V-max dehydroepiandrosterone = 30.0 fmoles; V-max estrone = 18.5 fmoles). Strain differences not the estrogen receptor content of hormone-dependent rat mammary tumors. In Wistar-Lewis rats the steroid alcohol sulfotransferase activity was at least 35 times higher than in the Sprague-Dawley strain. As was observed in the mouse mammary tumor, Sprague-Dawley rat neoplasms that grew in the absence of ovarian hormones contained significantly greater levels of the steroid alcohol sulfotransferase. Possible correlaion between presence of the steroid alcohol sulfotransferase and the estrogen receptor protein was observed in a limited number of human breast carcinomas.", "contents": "The steroid alcohol and estrogen sulfotransferases in rodent and human mammary tumors. Rodent and human mammary tumor systems were investigated to relate the steroid alcohol and estrogen sulfotransferase activities to the hormoanl dependency of the tumor as determined by estrogen receptor content. Unlike the normal mammary gland or the hyperplastic alveolar nodule, rodent mammary neoplasms displayed significant levels of these two sulfotransferases. In the hormone-independent mouse tumors produced from out-growth lines D1, D2, and D8, high dehydroepiandrosterone sulfotransferase activity was characteristic of the rapidity with which hyperplastic alveolar nodules developed into a neoplasms (V-max = 52.8 versus 1.8 fmoles/min/mg protein) while estrone sulfotransferase activity was either not detectable or low (V-max = 5.5 fmoles). After oophorectomy of mice bearing slowly developing tumors, both sulfotransferases in the nonregressing neoplasms showed marked increases in activity (V-max dehydroepiandrosterone = 30.0 fmoles; V-max estrone = 18.5 fmoles). Strain differences not the estrogen receptor content of hormone-dependent rat mammary tumors. In Wistar-Lewis rats the steroid alcohol sulfotransferase activity was at least 35 times higher than in the Sprague-Dawley strain. As was observed in the mouse mammary tumor, Sprague-Dawley rat neoplasms that grew in the absence of ovarian hormones contained significantly greater levels of the steroid alcohol sulfotransferase. Possible correlaion between presence of the steroid alcohol sulfotransferase and the estrogen receptor protein was observed in a limited number of human breast carcinomas."} {"id": "PMID:165884", "title": "Kinase and deaminase activity in a variety of subcutaneous mouse tumors.", "content": "Extracts of solid mouse tumors were examined for deoxycytidine kinase and deaminase activities. 1beta-D-Arabinofuranosylcytosine nucleotide was formed at a rate of 45 nmoles/hr by Glioma 26/57 and only 14 nmoles/hr by Ridgway osteogenic sarcoma. Deaminase activity was highest in Lewis lung (114 nmoles of 1-Beta-D-arabinofurano-syluridine formed per hr) and in CaD2 (104 nmoles of u-beta-D-arabinofuranosyluridine formed per hr). Deaminase activity in tumor extracts is sensitive to freezing, while deaminase activity in monkey serum is not. It was observed that kinase activity varies by as much as 50% in different cell lines of the same tumor. In the presence of tetrahydrouridine, kinase activity was significantly increased in most of the tumors studied.", "contents": "Kinase and deaminase activity in a variety of subcutaneous mouse tumors. Extracts of solid mouse tumors were examined for deoxycytidine kinase and deaminase activities. 1beta-D-Arabinofuranosylcytosine nucleotide was formed at a rate of 45 nmoles/hr by Glioma 26/57 and only 14 nmoles/hr by Ridgway osteogenic sarcoma. Deaminase activity was highest in Lewis lung (114 nmoles of 1-Beta-D-arabinofurano-syluridine formed per hr) and in CaD2 (104 nmoles of u-beta-D-arabinofuranosyluridine formed per hr). Deaminase activity in tumor extracts is sensitive to freezing, while deaminase activity in monkey serum is not. It was observed that kinase activity varies by as much as 50% in different cell lines of the same tumor. In the presence of tetrahydrouridine, kinase activity was significantly increased in most of the tumors studied."} {"id": "PMID:165885", "title": "Development of a 3T3-like line from an embryo culture of an inbred strain of Syrian golden hamster.", "content": "An embryo culture of an inbred strain of Syrian hamster developed into a permanent cell line under the \"3T3\" 3 X 10-5 cells/60-mm dish. The resulting cell line had properties very similar to those of the mouse 3T3 series and was named HAMS 3T3. The cell showed density-dependent inhibition of division with a saturation density of 1.0 to 1.2 x 10-6 cells/60-mm dish or 4.5 to 5.5 x 10-4 cells/sq cm. Addition of fresh medium containing 5 or 10% fetal calf serum to a confluent culture induced DNA synthesis in 18 hr with subsequent cell division. Cells were hyperdiploid with a mode of 45 chromosomes (80% of the cells). When cells at the 60th passage were injected into the skin or cheek pouch of an inbred hamster of the same strain as that from which they were derived, they produced a benign tumor that regressed after 3 weeks. Morphological transformation was obtained by infection with the Moloney strain of murine sarcoma virus.", "contents": "Development of a 3T3-like line from an embryo culture of an inbred strain of Syrian golden hamster. An embryo culture of an inbred strain of Syrian hamster developed into a permanent cell line under the \"3T3\" 3 X 10-5 cells/60-mm dish. The resulting cell line had properties very similar to those of the mouse 3T3 series and was named HAMS 3T3. The cell showed density-dependent inhibition of division with a saturation density of 1.0 to 1.2 x 10-6 cells/60-mm dish or 4.5 to 5.5 x 10-4 cells/sq cm. Addition of fresh medium containing 5 or 10% fetal calf serum to a confluent culture induced DNA synthesis in 18 hr with subsequent cell division. Cells were hyperdiploid with a mode of 45 chromosomes (80% of the cells). When cells at the 60th passage were injected into the skin or cheek pouch of an inbred hamster of the same strain as that from which they were derived, they produced a benign tumor that regressed after 3 weeks. Morphological transformation was obtained by infection with the Moloney strain of murine sarcoma virus."} {"id": "PMID:165886", "title": "Amino acid and sugar transport incells permissively infected with simian virus 40.", "content": "Transport of alpha-aminoisobutyric acid and 2-deoxy-D-glucose in African green monkey kidney cells was measured 8 to 100 hr following permissive simian virus 40 infection. No differences in transport were detected during the time-period studies, and no significant differences were seen between the apparent Michaelis-Menten constants of normal and virally infected cells. The absence of transport enhancement in permissive simian virus 40 infection suggests that the augmented transport of viral-transformed cell lines devolves upon altered host genome function.", "contents": "Amino acid and sugar transport incells permissively infected with simian virus 40. Transport of alpha-aminoisobutyric acid and 2-deoxy-D-glucose in African green monkey kidney cells was measured 8 to 100 hr following permissive simian virus 40 infection. No differences in transport were detected during the time-period studies, and no significant differences were seen between the apparent Michaelis-Menten constants of normal and virally infected cells. The absence of transport enhancement in permissive simian virus 40 infection suggests that the augmented transport of viral-transformed cell lines devolves upon altered host genome function."} {"id": "PMID:165887", "title": "5alpha-dihydrotestosterone-binding proteins and androgen sensitivity in prostatic cancers of Copenhangen rats.", "content": "A line (R-3327-A) of androgen-insensitive squamous cell carcinomas of the prostate of Copenhagen rats has been derived from an established line (R-3327) of androgen-responsive tumors R-3327 A tummors have a growth rate of approximately 10 times that of R-3327. The response of R=3327 A to hormonal environment has been determined by measuring the growth rate of the tumor transplanted to males, females, and castrated males. No great differences were observed. The metabolism of testosterone by tumore samples was studied following s.c. injections of the labeled steroid. The results show very little 5alpha-reduction of testosterone compared with that obtained in the prostate gland itself, as well as in the androgen-sensitive R-3327 tumors. A comparison of the presence of 17beta-hydroxy-5alpha-androstan-3-one-binding proteins in cytoplasmic extracts from both lines of tumors shows that the receptor proteins are present only in the androgen-sensitive R-3327 and not in the androgen-insensitive R-3327 A. The levels of the receptor proteins in R-3327 tumors are higher in tumors borne by male than by female animals, and castration of males decreases the amount of 17beta-hydroxy-5alpha-androstan-3-one binding.", "contents": "5alpha-dihydrotestosterone-binding proteins and androgen sensitivity in prostatic cancers of Copenhangen rats. A line (R-3327-A) of androgen-insensitive squamous cell carcinomas of the prostate of Copenhagen rats has been derived from an established line (R-3327) of androgen-responsive tumors R-3327 A tummors have a growth rate of approximately 10 times that of R-3327. The response of R=3327 A to hormonal environment has been determined by measuring the growth rate of the tumor transplanted to males, females, and castrated males. No great differences were observed. The metabolism of testosterone by tumore samples was studied following s.c. injections of the labeled steroid. The results show very little 5alpha-reduction of testosterone compared with that obtained in the prostate gland itself, as well as in the androgen-sensitive R-3327 tumors. A comparison of the presence of 17beta-hydroxy-5alpha-androstan-3-one-binding proteins in cytoplasmic extracts from both lines of tumors shows that the receptor proteins are present only in the androgen-sensitive R-3327 and not in the androgen-insensitive R-3327 A. The levels of the receptor proteins in R-3327 tumors are higher in tumors borne by male than by female animals, and castration of males decreases the amount of 17beta-hydroxy-5alpha-androstan-3-one binding."} {"id": "PMID:165888", "title": "Virion-associated and cellular RNA methylase activity in normal and neoplastic mammary tissue from mammary tumor virus-infected and -uninfected mice.", "content": "A comparison of cellular RNA methylase activities and patterns between normal and neoplastic mouse mammary tissue indicated the following. The rna methylases of mammary tumor tissue extracts are qualitatively different from those of normal lactating mammary tissue, based on differences in extent of methylation; the normal lactating tissue extracts have a greater capacity of methylate RNA than do the tumor extracts studied to date. There is no correlation between capacity and either the malignant state or the etiological agent. There is a qualitative effect on methylation patterns attributable to the presence of virus. Finally, both the etiological agent, mouse mammary tumor virus, and its putative nucleoprotein core, intracytoplasmic A particles, have a N-2-guanine RNA methyltransferase integrally associated with them. These conclusions are consistent with the aberrant nucleic acid methylation hypothesis, with the reservation that aberrant does not imply hypermethylation.", "contents": "Virion-associated and cellular RNA methylase activity in normal and neoplastic mammary tissue from mammary tumor virus-infected and -uninfected mice. A comparison of cellular RNA methylase activities and patterns between normal and neoplastic mouse mammary tissue indicated the following. The rna methylases of mammary tumor tissue extracts are qualitatively different from those of normal lactating mammary tissue, based on differences in extent of methylation; the normal lactating tissue extracts have a greater capacity of methylate RNA than do the tumor extracts studied to date. There is no correlation between capacity and either the malignant state or the etiological agent. There is a qualitative effect on methylation patterns attributable to the presence of virus. Finally, both the etiological agent, mouse mammary tumor virus, and its putative nucleoprotein core, intracytoplasmic A particles, have a N-2-guanine RNA methyltransferase integrally associated with them. These conclusions are consistent with the aberrant nucleic acid methylation hypothesis, with the reservation that aberrant does not imply hypermethylation."} {"id": "PMID:165889", "title": "In vitro transformation of hamster cells by herpes simplex virus type 2 from human prostatic cancer cells.", "content": "A cell-associated herpes simplex virus type 2 found in a human prostatic carcinoma induced in vitro transformation of hamster embryo cells. The transformed cells (YW-74) have been shown to be hamster cells by karyotype analysis. Their epithelial morphology and growth pattern, which are different from the parental cell, have remained stable through cell passages. The presence of herpesvirus antigens in the transformed cells was determined by specific immunofluorescence and colony inhibition tests. Immunofluorescence staining with specific anti-herpes simplex virus type 2 serum showed an intense and distinctive nuclear and perinuclear fluorescence in about 95% of the transformed cells. In addition, exposure of these transformed cells to herpes simplex virus type 2-sensitized lymphocytes resulted in inhibition of growth and colony formation, while no effect was seen with nonsensitized lymphocytes. Both observations are consistent with the involvement of herpesvirus type 2 in the transformation event. This virus, which does not produce a lytic infection and is not found either in extracellular spaces or supernatant fluid of the transformed cell cultures, is unique in the fact that it is cell associated, noncytopathogenic, and capable of transforming cells in vitro, and its antigens are clearly demonstrated in the transformed cells.", "contents": "In vitro transformation of hamster cells by herpes simplex virus type 2 from human prostatic cancer cells. A cell-associated herpes simplex virus type 2 found in a human prostatic carcinoma induced in vitro transformation of hamster embryo cells. The transformed cells (YW-74) have been shown to be hamster cells by karyotype analysis. Their epithelial morphology and growth pattern, which are different from the parental cell, have remained stable through cell passages. The presence of herpesvirus antigens in the transformed cells was determined by specific immunofluorescence and colony inhibition tests. Immunofluorescence staining with specific anti-herpes simplex virus type 2 serum showed an intense and distinctive nuclear and perinuclear fluorescence in about 95% of the transformed cells. In addition, exposure of these transformed cells to herpes simplex virus type 2-sensitized lymphocytes resulted in inhibition of growth and colony formation, while no effect was seen with nonsensitized lymphocytes. Both observations are consistent with the involvement of herpesvirus type 2 in the transformation event. This virus, which does not produce a lytic infection and is not found either in extracellular spaces or supernatant fluid of the transformed cell cultures, is unique in the fact that it is cell associated, noncytopathogenic, and capable of transforming cells in vitro, and its antigens are clearly demonstrated in the transformed cells."} {"id": "PMID:165890", "title": "Uncertainties in the use of periodate oxidation for determination of dextran structure.", "content": "A glucan of high molecular weight isolated from stale sugar-cane, and previously shown to have a marked effect on sucrose crystallisation processes-1, is a relatively linear dextran. Approximately 96-97% of its D-glucose residues are involved in (1 yields 6)-alpha-D linkages and constitute the linear backbone of the polymer. The remaining 3-4% of D-glucose residues form branch-points by (1 yields 3)-alpha-D linkages. The periodate-oxidation technique, which has been extensively used by other workers to determine dextran structure, gave erroneous results when applied to the dextran from stale sugar-cane.", "contents": "Uncertainties in the use of periodate oxidation for determination of dextran structure. A glucan of high molecular weight isolated from stale sugar-cane, and previously shown to have a marked effect on sucrose crystallisation processes-1, is a relatively linear dextran. Approximately 96-97% of its D-glucose residues are involved in (1 yields 6)-alpha-D linkages and constitute the linear backbone of the polymer. The remaining 3-4% of D-glucose residues form branch-points by (1 yields 3)-alpha-D linkages. The periodate-oxidation technique, which has been extensively used by other workers to determine dextran structure, gave erroneous results when applied to the dextran from stale sugar-cane."} {"id": "PMID:165896", "title": "The fine structure of the oocyte of bankia australis (teredinidae, bivalvia) before and after fertilization.", "content": "The fine structure of the oocyte of Bankia australis is compared with that of other bivalve oocytes. It was observed that following fertilization, the microvilli changed their spatial organisation and behaviour towards sperm, the cortical granules disappeared in regions of high concentrations of supernumerary sperm, and the mitochondria apparently stated to divide.", "contents": "The fine structure of the oocyte of bankia australis (teredinidae, bivalvia) before and after fertilization. The fine structure of the oocyte of Bankia australis is compared with that of other bivalve oocytes. It was observed that following fertilization, the microvilli changed their spatial organisation and behaviour towards sperm, the cortical granules disappeared in regions of high concentrations of supernumerary sperm, and the mitochondria apparently stated to divide."} {"id": "PMID:165897", "title": "The fine structure of the epidermis of two species of salmonid fish, the Atlantic salmon (Salmo salar l.) and the brown trout (Salmo trutta L.). I. General organization and filament-containing cells.", "content": "The fine structure of the epidermis or two species of salmonid fish has been described. Gross characteristics have been noted along with many apparent differences in the epidermis of different body regions of the fish. The major cell type is the filament-containing cell and this has been described in detail. The major inclusions of the cell are the tonofilaments. Differences in basal, mid-epidermal and periphal filament-c0ntaingcells have been characterized. Comparisons of fish epidermis with that of other vertebrates has been made.", "contents": "The fine structure of the epidermis of two species of salmonid fish, the Atlantic salmon (Salmo salar l.) and the brown trout (Salmo trutta L.). I. General organization and filament-containing cells. The fine structure of the epidermis or two species of salmonid fish has been described. Gross characteristics have been noted along with many apparent differences in the epidermis of different body regions of the fish. The major cell type is the filament-containing cell and this has been described in detail. The major inclusions of the cell are the tonofilaments. Differences in basal, mid-epidermal and periphal filament-c0ntaingcells have been characterized. Comparisons of fish epidermis with that of other vertebrates has been made."} {"id": "PMID:165898", "title": "Morphological changes in cultured mammalian cells: prevention by the calcium ionophore A23187.", "content": "The morphological changes induced by butyrate in HeLa cells and by monobutyryl or dibutyryl cAMP in CHO cells are prevented by micromolar concentrations of the divalent cation ionophore A23187. The ionophore is unable to prevent such changes in medium from which calcium is omitted. At slightly higher (but nontoxic) concentrations, the ionophore inhibits the butyrate-mediated induction of the ganglioside biosynthetic enzyme, sialyltransferase, in HeLa. In CHO, sialyltransferase activity is normally high and not altered by any of the compounds tested.", "contents": "Morphological changes in cultured mammalian cells: prevention by the calcium ionophore A23187. The morphological changes induced by butyrate in HeLa cells and by monobutyryl or dibutyryl cAMP in CHO cells are prevented by micromolar concentrations of the divalent cation ionophore A23187. The ionophore is unable to prevent such changes in medium from which calcium is omitted. At slightly higher (but nontoxic) concentrations, the ionophore inhibits the butyrate-mediated induction of the ganglioside biosynthetic enzyme, sialyltransferase, in HeLa. In CHO, sialyltransferase activity is normally high and not altered by any of the compounds tested."} {"id": "PMID:165899", "title": "An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion.", "content": "When cells of the established preadipose line 3T3-L1 enter a resting state, they accumulate triglyceride and convert to adipose cells. The adipose conversion is brought about by a large increase in the rate of triglyceride synthesis, as measured by the incorporation rate of labeled palmitate, acetate, and glucose. In a resting 3T3 subline which dose not undergo the adipose conversion, the rate of triglyceride synthesis from these precursors is very low, and similar to that of growing 3T3-L1 cells, before their adipose conversion begins. If 3T3-L1 cells incorporate bromodeoxyuridine during growth, triglyceride synthesis does not increase when the cells reach a stationary state, and triglycerides do not accumulate. As would be expected from their known actions on tissue adipose cells, lipogenic and lipolytic hormones and drugs affect the rate of synthesis and accumulation of triglyceride by 3T3-L1 cells, but in contrast to bromodeoxyuridine, these modulating agents do not seem to affect the proportion of cells which undergoes the adipose conversion. Insulin markedly increases the rate of synthesis and accumulation of triglyceride by fatty 3T3-L1 cells, and produces a related increase in cell protein content. Of 20 randomly selected clones isolated from the original 3T3 stock, 19 are able to convert to adipose cells. The probability of such a conversion varies greatly among the different clones, in most cases being much lower than for 3T3-L1; but once the conversion takes place, the adipose cells produced from all of the 19 clones appear similar. The adipose conversion would seem to depend on an on-off switch, which is on with a different probability in different clones. This probability is quasistably inherited by the clonal progeny.", "contents": "An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. When cells of the established preadipose line 3T3-L1 enter a resting state, they accumulate triglyceride and convert to adipose cells. The adipose conversion is brought about by a large increase in the rate of triglyceride synthesis, as measured by the incorporation rate of labeled palmitate, acetate, and glucose. In a resting 3T3 subline which dose not undergo the adipose conversion, the rate of triglyceride synthesis from these precursors is very low, and similar to that of growing 3T3-L1 cells, before their adipose conversion begins. If 3T3-L1 cells incorporate bromodeoxyuridine during growth, triglyceride synthesis does not increase when the cells reach a stationary state, and triglycerides do not accumulate. As would be expected from their known actions on tissue adipose cells, lipogenic and lipolytic hormones and drugs affect the rate of synthesis and accumulation of triglyceride by 3T3-L1 cells, but in contrast to bromodeoxyuridine, these modulating agents do not seem to affect the proportion of cells which undergoes the adipose conversion. Insulin markedly increases the rate of synthesis and accumulation of triglyceride by fatty 3T3-L1 cells, and produces a related increase in cell protein content. Of 20 randomly selected clones isolated from the original 3T3 stock, 19 are able to convert to adipose cells. The probability of such a conversion varies greatly among the different clones, in most cases being much lower than for 3T3-L1; but once the conversion takes place, the adipose cells produced from all of the 19 clones appear similar. The adipose conversion would seem to depend on an on-off switch, which is on with a different probability in different clones. This probability is quasistably inherited by the clonal progeny."} {"id": "PMID:165900", "title": "The 5' terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus.", "content": "The 5' terminal structure of the mRNA synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus in the presence of S-adenosyl-L-methione consists of 7-methyl guanosine linked to 2'-O-methyl adenosine through a 5'-5' pyrophosphate bond as m7G(5')ppp(5')A-m-p ... The alpha and beta phosphated of GTP and alpha phosphate of ATP are incorporated into the blocked 5' terminal structure.", "contents": "The 5' terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus. The 5' terminal structure of the mRNA synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus in the presence of S-adenosyl-L-methione consists of 7-methyl guanosine linked to 2'-O-methyl adenosine through a 5'-5' pyrophosphate bond as m7G(5')ppp(5')A-m-p ... The alpha and beta phosphated of GTP and alpha phosphate of ATP are incorporated into the blocked 5' terminal structure."} {"id": "PMID:165901", "title": "Methylated and blocked 5' termini in vesicular stomatitis virus in vivo mRNAs.", "content": "Methyl groups derived from 3H-methyl methionine were incorporated into vesicular stomatitis virus (VSV) MRNAs isolated from infected cells. Sequential degradation of the 12-18S viral mRNA species with ribonuclease T2, penicillium nuclease, and alkaline phosphatase yielded a single 3H-labeled dinucleotide. A similar resistant 32P-labeled fragment was obtained by digesting VSV mRNA uniformly labeled with 32P. This methylated and blocked oligomer was further cleaved with nucleotide pyrophosphatase, yielding two methylated 5' nucleotides. We postulate that the 5' terminal structure of the vivo 12-18S VSV mRNA contains 7-methylguanosine linked by a 5'-5' pyrophosphate bond to a methylated derivative of adenosine. In contrast to the mRNAs (+ strand), the VSV genome RNA ( MINUS STRAND) IS NOT BLOCKED.", "contents": "Methylated and blocked 5' termini in vesicular stomatitis virus in vivo mRNAs. Methyl groups derived from 3H-methyl methionine were incorporated into vesicular stomatitis virus (VSV) MRNAs isolated from infected cells. Sequential degradation of the 12-18S viral mRNA species with ribonuclease T2, penicillium nuclease, and alkaline phosphatase yielded a single 3H-labeled dinucleotide. A similar resistant 32P-labeled fragment was obtained by digesting VSV mRNA uniformly labeled with 32P. This methylated and blocked oligomer was further cleaved with nucleotide pyrophosphatase, yielding two methylated 5' nucleotides. We postulate that the 5' terminal structure of the vivo 12-18S VSV mRNA contains 7-methylguanosine linked by a 5'-5' pyrophosphate bond to a methylated derivative of adenosine. In contrast to the mRNAs (+ strand), the VSV genome RNA ( MINUS STRAND) IS NOT BLOCKED."} {"id": "PMID:165902", "title": "Differential cytotoxic acitivity of anticollagen serum on rat osteoblasts and fibroblasts in tissue culture.", "content": "Rat skin fibroblasts grown in tissue culture were lysed by anti-rat-tail collagen serum and antibodies to the ordered collagen-like synthetic polymer (Pro-Gly-Pro)-n. This cytotoxic effect is complement-dependent and occurs only if the fibroblasts were pretreated with trypsin. These anti-sera have very little cytotoxicity on cultured rat osteoblasts. This differential cytotoxicity is not due to differential binding of anticollagen serum to the cells. Both osteoblasts and skin fibroblasts bind the anticollagen serum as was demonstrated by fluorescent immunoglobulin.", "contents": "Differential cytotoxic acitivity of anticollagen serum on rat osteoblasts and fibroblasts in tissue culture. Rat skin fibroblasts grown in tissue culture were lysed by anti-rat-tail collagen serum and antibodies to the ordered collagen-like synthetic polymer (Pro-Gly-Pro)-n. This cytotoxic effect is complement-dependent and occurs only if the fibroblasts were pretreated with trypsin. These anti-sera have very little cytotoxicity on cultured rat osteoblasts. This differential cytotoxicity is not due to differential binding of anticollagen serum to the cells. Both osteoblasts and skin fibroblasts bind the anticollagen serum as was demonstrated by fluorescent immunoglobulin."} {"id": "PMID:165908", "title": "Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man.", "content": "The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man.", "contents": "Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man. The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man."} {"id": "PMID:165909", "title": "Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology.", "content": "Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with \"unstable angina pectoris\", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with \"unstable angina\" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.", "contents": "Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with \"unstable angina pectoris\", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with \"unstable angina\" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small."} {"id": "PMID:165910", "title": "Molar absorptivities of beta-NADH and beta-NAD at 260 nm.", "content": "To determine the molar absorptivities of beta-NADH and beta-NAD at 260 nm, we purified the reduced form of the coenzyme by repeated anion-exchange chromatography. A NADH preparation was so obtained for which the 260 nm/340 nm absorbance ratio was 2.265. When calculated with epsilon 340 beta-NADH = 6.22 times 10-3 for beta-NADH at 260 nm and 25 degrees C, a molar absorptivity of 14.1 times 10-3 liter - mol minus 1 - cm minus 1 resulted from this quotient. By use of the lactate dehydrogenase or glycerol-3-phosphate dehydrogenase assay, respectively, and referring to the new absorption coefficient for NADH at 260 nm, the molar absorptivity of beta-NAD at 260 nm and 25 degrees C was established to be 17.4 times 10-3 liter - mol minus 1 - cm minus 1. The values observed are lower than those reported thus far.", "contents": "Molar absorptivities of beta-NADH and beta-NAD at 260 nm. To determine the molar absorptivities of beta-NADH and beta-NAD at 260 nm, we purified the reduced form of the coenzyme by repeated anion-exchange chromatography. A NADH preparation was so obtained for which the 260 nm/340 nm absorbance ratio was 2.265. When calculated with epsilon 340 beta-NADH = 6.22 times 10-3 for beta-NADH at 260 nm and 25 degrees C, a molar absorptivity of 14.1 times 10-3 liter - mol minus 1 - cm minus 1 resulted from this quotient. By use of the lactate dehydrogenase or glycerol-3-phosphate dehydrogenase assay, respectively, and referring to the new absorption coefficient for NADH at 260 nm, the molar absorptivity of beta-NAD at 260 nm and 25 degrees C was established to be 17.4 times 10-3 liter - mol minus 1 - cm minus 1. The values observed are lower than those reported thus far."} {"id": "PMID:165911", "title": "Peripheral resistance to thyroxine: a cause of short stature in a boy without goitre.", "content": "A euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 mug of thyroxine or 225 mug of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed.", "contents": "Peripheral resistance to thyroxine: a cause of short stature in a boy without goitre. A euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 mug of thyroxine or 225 mug of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed."} {"id": "PMID:165912", "title": "Effect of oral thyrotrophin-releasing hormone on serum thyroxine in growth hormone deficient and normal children.", "content": "Oral administration of synthetic TRH in a dose of 80 mg/1-73 m-2 at 0 and 12 h to normal and constitutionally small children caused a significant increase of total serum thyroxine (T4) within 6-24 h. The mean maximal T4 increment was +3-7 plus or minus 1-1 and +3-8 plus or minus 1-2 mug/dl (mean plus or minus 1 SD) respectively in the two groups. Of seventeen euthyroid GH deficient children, fifteen showed a normal and two patients a slightly subnormal response. Of fifteen hypothyroid GH deficient children nine had a prompt and normal increase of serum T4 indicating primary TRH deficiency. Two had a delayed T4 response and four had no response, even after prolonged stimulation. The localization of the primary defect in these latter subjects with severe hypothyroidism can not be made by measuring T4 only, since the thyroid gland may become unresponsive to TSH after longstanding TSH deficiency. TSH measurements are necessary in these circumstances for a clear localization of the primary defect. One GH deficient patient with hypothalamic TRH deficiency was treated with high oral TRH doses for 7 months and showed no side effects.", "contents": "Effect of oral thyrotrophin-releasing hormone on serum thyroxine in growth hormone deficient and normal children. Oral administration of synthetic TRH in a dose of 80 mg/1-73 m-2 at 0 and 12 h to normal and constitutionally small children caused a significant increase of total serum thyroxine (T4) within 6-24 h. The mean maximal T4 increment was +3-7 plus or minus 1-1 and +3-8 plus or minus 1-2 mug/dl (mean plus or minus 1 SD) respectively in the two groups. Of seventeen euthyroid GH deficient children, fifteen showed a normal and two patients a slightly subnormal response. Of fifteen hypothyroid GH deficient children nine had a prompt and normal increase of serum T4 indicating primary TRH deficiency. Two had a delayed T4 response and four had no response, even after prolonged stimulation. The localization of the primary defect in these latter subjects with severe hypothyroidism can not be made by measuring T4 only, since the thyroid gland may become unresponsive to TSH after longstanding TSH deficiency. TSH measurements are necessary in these circumstances for a clear localization of the primary defect. One GH deficient patient with hypothalamic TRH deficiency was treated with high oral TRH doses for 7 months and showed no side effects."} {"id": "PMID:165913", "title": "Comparison of the effects of ethinyl oestradiol and conjugated equine oestrogens in oophorectomized women.", "content": "Seventeen oophorectomized women were treated for 3 month periods, in random sequence, with ethinyl oestradiol 20 and 50 mug daily and conjugated equine oestrogens (Premarin)0-625 and 1-25 mg daily. The serum cholesterol, clot lysis time, plasma fibrinogen, platelet adhesiveness and activated partial thromboplastin time remained unchanged throughout the different oestrogen regimes. There was a significant rise of serum triglyceride levels on both doses of ethinyl oestradiol but no significant change with Premarin. Serum luteinizing hormone levels were depressed most by ethinyl oestradiol 50 mug daily, although no down to the levels in premenopausal women.", "contents": "Comparison of the effects of ethinyl oestradiol and conjugated equine oestrogens in oophorectomized women. Seventeen oophorectomized women were treated for 3 month periods, in random sequence, with ethinyl oestradiol 20 and 50 mug daily and conjugated equine oestrogens (Premarin)0-625 and 1-25 mg daily. The serum cholesterol, clot lysis time, plasma fibrinogen, platelet adhesiveness and activated partial thromboplastin time remained unchanged throughout the different oestrogen regimes. There was a significant rise of serum triglyceride levels on both doses of ethinyl oestradiol but no significant change with Premarin. Serum luteinizing hormone levels were depressed most by ethinyl oestradiol 50 mug daily, although no down to the levels in premenopausal women."} {"id": "PMID:165914", "title": "The effect of yttrium-90 implantation on endocrine function and visual fields in patients with \"functionless\" pituitary tumors, with biopsy and radiological findings.", "content": "Thirty patients with symptoms from \"functionless\" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of \"functionless\" pituitary tumour. The \"supressive\" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.", "contents": "The effect of yttrium-90 implantation on endocrine function and visual fields in patients with \"functionless\" pituitary tumors, with biopsy and radiological findings. Thirty patients with symptoms from \"functionless\" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of \"functionless\" pituitary tumour. The \"supressive\" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function."} {"id": "PMID:165915", "title": "Circulating levels of corticotrophin and cortisol after infusions of L-DOPA, dopamine and noradrenaline, in man.", "content": "Intravenous infusions of noradrenaline and dopamine in normal saline, and L-dopa in sodium lactate, were given to seven patients with Parkinsonism, and to five healthy volunteers. Infusions of saline and lactate were given, in a similar manner, to six additional healthy volunteers, who formed a control group. Dopamine and noradrenaline were each given in gradually increasing doses, for periods of 4 min, until a 30% increase in systolic blood pressure had occurred. L-Dopa (320 mg) was given a constant rate of infusion over 80 min. Plasma fluorogenic corticosteroids (cortisol) increased with dopamine , and decreased with noradrenaline. These changes were significantly different from the control group in the case of noradrenaline only. ACTH values changed in a similar manner. L-Dopa produced a consistent rise in both ACTH and cortisol that was significantly different from control subjects. The implications of these observations are discussed.", "contents": "Circulating levels of corticotrophin and cortisol after infusions of L-DOPA, dopamine and noradrenaline, in man. Intravenous infusions of noradrenaline and dopamine in normal saline, and L-dopa in sodium lactate, were given to seven patients with Parkinsonism, and to five healthy volunteers. Infusions of saline and lactate were given, in a similar manner, to six additional healthy volunteers, who formed a control group. Dopamine and noradrenaline were each given in gradually increasing doses, for periods of 4 min, until a 30% increase in systolic blood pressure had occurred. L-Dopa (320 mg) was given a constant rate of infusion over 80 min. Plasma fluorogenic corticosteroids (cortisol) increased with dopamine , and decreased with noradrenaline. These changes were significantly different from the control group in the case of noradrenaline only. ACTH values changed in a similar manner. L-Dopa produced a consistent rise in both ACTH and cortisol that was significantly different from control subjects. The implications of these observations are discussed."} {"id": "PMID:165917", "title": "Hemihypertrophy of lower extremity associated with multifocal intraosseous hemangioma.", "content": "This is a case report of a child with hemangioma of the bones of the lower extremities. The evolution of the disease in several bones, during the period between infancy and maturity, and serial growth studies of the extremities and differences in length of bones reveals that in some cases the involved bone grew longer than its fellow, whereas in others it grew shorter. Histological examination of an epiphyseal plate demonstrates that hemangioma grew on either side of the plate.", "contents": "Hemihypertrophy of lower extremity associated with multifocal intraosseous hemangioma. This is a case report of a child with hemangioma of the bones of the lower extremities. The evolution of the disease in several bones, during the period between infancy and maturity, and serial growth studies of the extremities and differences in length of bones reveals that in some cases the involved bone grew longer than its fellow, whereas in others it grew shorter. Histological examination of an epiphyseal plate demonstrates that hemangioma grew on either side of the plate."} {"id": "PMID:165918", "title": "Lesions of the atlas and axis.", "content": "The atlas and axis support the head on the lower cervical spine while providing for considerable mobility in flexion, extension, rotation and lateral bending. The first two vertebrae also function as conduits for the cervical cord and vertebral arteries. Lesions of the atlas and axis, therefore, can cause instability with loss of support and encroachment on the upper cord and vertebral arteries, or less often stiffness with restricted motion. Congenital lesions of the occipito-cervical spine such as occipitalization of the atlas or accessory occipital vertebrae can constrict the upper cord with osseous, dural, or fibrous compression. Such encroachment on the cord at this level produces a varying array of clinical complaints and findings frequently difficult to interpret. Instability of the upper cervical spine can result from congenital, traumatic, inflammatory or neoplastic disruptions of the interlocking mechanism of the atlas and axis. Such factors as the loss of structural integrity of the dens or stretching or tearing of the transverse ligament can permit instability with cord involvement. Because of the serious potential of these lesions, patients with abnormalities of the atlas and axis require prompt recognition and treatment.", "contents": "Lesions of the atlas and axis. The atlas and axis support the head on the lower cervical spine while providing for considerable mobility in flexion, extension, rotation and lateral bending. The first two vertebrae also function as conduits for the cervical cord and vertebral arteries. Lesions of the atlas and axis, therefore, can cause instability with loss of support and encroachment on the upper cord and vertebral arteries, or less often stiffness with restricted motion. Congenital lesions of the occipito-cervical spine such as occipitalization of the atlas or accessory occipital vertebrae can constrict the upper cord with osseous, dural, or fibrous compression. Such encroachment on the cord at this level produces a varying array of clinical complaints and findings frequently difficult to interpret. Instability of the upper cervical spine can result from congenital, traumatic, inflammatory or neoplastic disruptions of the interlocking mechanism of the atlas and axis. Such factors as the loss of structural integrity of the dens or stretching or tearing of the transverse ligament can permit instability with cord involvement. Because of the serious potential of these lesions, patients with abnormalities of the atlas and axis require prompt recognition and treatment."} {"id": "PMID:165919", "title": "The GP as a psychiatric community resource.", "content": "One hundred pyschiatric inpatients were interviewed to determine their normal use of a family doctor and opinion about his value in aftercare. The ward team made a similar decision and when appropriate, a family doctor was approached about his willingness to undertake the aftercare. There were 54 patients who had a family doctor, 38 felt he could assist in aftercare. By contrast, the ward team seldom considered referral appropriate and family doctors were initially hostile to the concept. The demographic variables and attitudes underlying the views of patients, staff, and family doctors are discussed together with their implications for community care.", "contents": "The GP as a psychiatric community resource. One hundred pyschiatric inpatients were interviewed to determine their normal use of a family doctor and opinion about his value in aftercare. The ward team made a similar decision and when appropriate, a family doctor was approached about his willingness to undertake the aftercare. There were 54 patients who had a family doctor, 38 felt he could assist in aftercare. By contrast, the ward team seldom considered referral appropriate and family doctors were initially hostile to the concept. The demographic variables and attitudes underlying the views of patients, staff, and family doctors are discussed together with their implications for community care."} {"id": "PMID:165929", "title": "Fluorimetric determination of dipeptidyl carboxypeptidase. (angiotensin-I-converting enzyme).", "content": "A fluorimetric assay of dipeptidyl carboxypeptidase is described. It involves incubation at 37 degrees C with the substrate, Z-Phe-His-Leu, and reaction of the dipeptide His-Leu which is released upon enzymatic hydrolysis, with o-phthalaldehyde to yield a fluorescent compound. The method is simple, precise and sensitive. The assay in serum is conveniently performed on 20 mul samples. Normal values in human serum range from 0.04 to 0.22 U/l.", "contents": "Fluorimetric determination of dipeptidyl carboxypeptidase. (angiotensin-I-converting enzyme). A fluorimetric assay of dipeptidyl carboxypeptidase is described. It involves incubation at 37 degrees C with the substrate, Z-Phe-His-Leu, and reaction of the dipeptide His-Leu which is released upon enzymatic hydrolysis, with o-phthalaldehyde to yield a fluorescent compound. The method is simple, precise and sensitive. The assay in serum is conveniently performed on 20 mul samples. Normal values in human serum range from 0.04 to 0.22 U/l."} {"id": "PMID:165930", "title": "Leucocyte energy metabolism. V. Glycolytic and hexose monophosphate shunt enzymes in leucocytes from adults and newborn infants.", "content": "The activities of ATP-consuming and ATP-producing steps of the Embden-Meyerhof pathway, as well as other glycolytic enzymes (phosphoglucomutase and enolase) and glucose-6-phosphate dehydrogenase are lower in leucocytes from cord blood than in white cells from adults. These results are related to previous observations (reduced anaerobic glycolysis and nitroblue tetrazolium-test in leucocytes from newborn infants) and discussed in connection with the fact that newborn infants are more susceptible to infections than normal adults.", "contents": "Leucocyte energy metabolism. V. Glycolytic and hexose monophosphate shunt enzymes in leucocytes from adults and newborn infants. The activities of ATP-consuming and ATP-producing steps of the Embden-Meyerhof pathway, as well as other glycolytic enzymes (phosphoglucomutase and enolase) and glucose-6-phosphate dehydrogenase are lower in leucocytes from cord blood than in white cells from adults. These results are related to previous observations (reduced anaerobic glycolysis and nitroblue tetrazolium-test in leucocytes from newborn infants) and discussed in connection with the fact that newborn infants are more susceptible to infections than normal adults."} {"id": "PMID:165931", "title": "Enzymes of fructose metabolism in human kidney.", "content": "Activities of enzymes involved in fructose metabolism were measured in samples of human kidney cortex and medulla. The enzymes are ketohexokinase, aldolase, NAD- and NADP-dependent alcohol dehydrogenase, aldehyde dehydrogenase, triokinase and glycerate kinase; hexose biphosphatase and sorbitol dehydrogenase were also investigated. With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla. The enzyme levels in the medulla were low in comparison with the cortex.", "contents": "Enzymes of fructose metabolism in human kidney. Activities of enzymes involved in fructose metabolism were measured in samples of human kidney cortex and medulla. The enzymes are ketohexokinase, aldolase, NAD- and NADP-dependent alcohol dehydrogenase, aldehyde dehydrogenase, triokinase and glycerate kinase; hexose biphosphatase and sorbitol dehydrogenase were also investigated. With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla. The enzyme levels in the medulla were low in comparison with the cortex."} {"id": "PMID:165932", "title": "Enzymes of fructose metabolism in human small intestine mucosa.", "content": "The enzyme activities involved in fructose metabolism were measured in human intestine mucosa. Mucosa of the following gut sections were used: duodenum, jejunum, jejunum in the region of the flexura duodenojejunalis, jejunum distal region, ileum middle region and ileum in the region of the valvula ileo coecalis. Ketohexokinase, aldolase, alcohol dehydrogenases NAD- and NADP- dependent were found in all gut sections. The activity of aldehyde dehydrogenase was low in all sections tested. Triokinase could be found only in the duodenum and jejunum region and was absent in the ileum. Glycerate kinase was not present in the human intestine mucosa.", "contents": "Enzymes of fructose metabolism in human small intestine mucosa. The enzyme activities involved in fructose metabolism were measured in human intestine mucosa. Mucosa of the following gut sections were used: duodenum, jejunum, jejunum in the region of the flexura duodenojejunalis, jejunum distal region, ileum middle region and ileum in the region of the valvula ileo coecalis. Ketohexokinase, aldolase, alcohol dehydrogenases NAD- and NADP- dependent were found in all gut sections. The activity of aldehyde dehydrogenase was low in all sections tested. Triokinase could be found only in the duodenum and jejunum region and was absent in the ileum. Glycerate kinase was not present in the human intestine mucosa."} {"id": "PMID:165933", "title": "A 3'-deoxymononucleotide-producing nuclease from the marine sponge Verongia aerophoba. I. Purification.", "content": "A four-step procedure for purification of a nuclease from the keratinous sponge Verongia aerophoba is described. The extracted material is lyophilized, acidified, and subjected to chromatography on Sephadex, hydroxyapatite, and phosphocellulose. The nuclease is purified about 1,000-fold from the crude extract and approximately 1,600-fold from concomitant acid RNase. Phosphodiesterase is lost after chromatography on Sephadex. The purified enzyme solution contains one single activity as determined by polyacrylamide gel electrophoresis.", "contents": "A 3'-deoxymononucleotide-producing nuclease from the marine sponge Verongia aerophoba. I. Purification. A four-step procedure for purification of a nuclease from the keratinous sponge Verongia aerophoba is described. The extracted material is lyophilized, acidified, and subjected to chromatography on Sephadex, hydroxyapatite, and phosphocellulose. The nuclease is purified about 1,000-fold from the crude extract and approximately 1,600-fold from concomitant acid RNase. Phosphodiesterase is lost after chromatography on Sephadex. The purified enzyme solution contains one single activity as determined by polyacrylamide gel electrophoresis."} {"id": "PMID:165982", "title": "Insulin: interaction with membrane receprots and relationship to cyclic purine nucleotides and cell growth.", "content": "Insulin action is discussed with emphasis on events that occur at the plasma membrane. A summary is presented of previous studies which indicate that the insulin receptor of fat and liver cells is a large glycoprotein, partially buried in the outer surface of the plasma membrane, with a high (K-D approximately 10-10 M) and specific affinity for insulin. The participation of membrane phospholipids in the binding of insulin and the role of sialic acid residues in the transmission of the insulin binding signal are discussed. The relation of insulin action to its effects on cyclic nucleotide levels is explored. On the one hand, insulin action (glucose transport) is inhibited by compounds (cholera toxin, ACTH, glucagon and L-norepinephrine) that stimulate adenylate cyclase; conversely, insulin both inhibits the lipolytic action of these compounds, and raises cellular levels of cyclic GMP. An hypothesis is presented whereby a single cyclase species may be responsible for the formation of either cyclic AMP or cyclic GMP, depending on the nature of the hormone stimulus. The role of membrane phosphorylation in the action of insulin is discussed in the context of experiments demonstrating a specific inhibition by ATP of insulin-mediated glucose transport, in association with the phosphorylation of two specific membrane proteins. The ability of insulin to modulate cyclic nucleotide levels in cultured cells and to act as a growth factor is discussed. Insulin stimulates DNA synthesis and the uptake of alpha-aminoisobutyric acid in human fibroblasts, which effects are also mediated by epidermal growth factor. Insulin acts at concentrations much higher than those obtained in vivo, whereas epidermal growth factor acts at concentrations thought to be physiological. The insulin binding sites (K-D is approximately equal to 10-9 M) related to growth, and observed both in human fibroblasts and in lectin-stimulated and leukemic human lymphocytes would not be appreciably occupied at physiological insulin concentrations. The implications of such 'low affinity' binding sites for insulin are discussed in relation to the action of other growth factors.", "contents": "Insulin: interaction with membrane receprots and relationship to cyclic purine nucleotides and cell growth. Insulin action is discussed with emphasis on events that occur at the plasma membrane. A summary is presented of previous studies which indicate that the insulin receptor of fat and liver cells is a large glycoprotein, partially buried in the outer surface of the plasma membrane, with a high (K-D approximately 10-10 M) and specific affinity for insulin. The participation of membrane phospholipids in the binding of insulin and the role of sialic acid residues in the transmission of the insulin binding signal are discussed. The relation of insulin action to its effects on cyclic nucleotide levels is explored. On the one hand, insulin action (glucose transport) is inhibited by compounds (cholera toxin, ACTH, glucagon and L-norepinephrine) that stimulate adenylate cyclase; conversely, insulin both inhibits the lipolytic action of these compounds, and raises cellular levels of cyclic GMP. An hypothesis is presented whereby a single cyclase species may be responsible for the formation of either cyclic AMP or cyclic GMP, depending on the nature of the hormone stimulus. The role of membrane phosphorylation in the action of insulin is discussed in the context of experiments demonstrating a specific inhibition by ATP of insulin-mediated glucose transport, in association with the phosphorylation of two specific membrane proteins. The ability of insulin to modulate cyclic nucleotide levels in cultured cells and to act as a growth factor is discussed. Insulin stimulates DNA synthesis and the uptake of alpha-aminoisobutyric acid in human fibroblasts, which effects are also mediated by epidermal growth factor. Insulin acts at concentrations much higher than those obtained in vivo, whereas epidermal growth factor acts at concentrations thought to be physiological. The insulin binding sites (K-D is approximately equal to 10-9 M) related to growth, and observed both in human fibroblasts and in lectin-stimulated and leukemic human lymphocytes would not be appreciably occupied at physiological insulin concentrations. The implications of such 'low affinity' binding sites for insulin are discussed in relation to the action of other growth factors."} {"id": "PMID:165983", "title": "Relation of insulin receptors to insulin resistance.", "content": "The status of insulin-receptor interactions in a variety of insulin-resistant states is reviewed. Utilizing large adipocytes from adult rats and small fat cells from young rats, we have conducted a series of in vitro experiments in an attempt to determine the cellular alteration(s) responsible for the insulin resistance associated with obesity. Stimulation of glucose oxidation by insulin is reduced in large cells. Studies using a mimicker of insulin action, spermine, as well as measurements of 125I-insulin binding to large and small cells indicate that receptor number and affinity are not responsible for hormone resistance. Furthermore, when rapid and direct measurements of sugar uptake were made, insulin stimulation was virtually identical in both cell types. These findings indicate that large adipocytes have an efficient insulin-responsive D-glucose transport system and suggest that the apparent hormone resistance may be due to alterations in intracellular glucose metabolism. It has been proposed that altered insulin-receptor interaction underlies the insulin resistance of human obesity. We have investigated this particular aspect of insulin action by 125I-insulin binding studies. Similar numbers of insulin receptors per cell and affinity for insulin were observed in adipocytes obtained from normal weight subjects and morbidly obese patients. Thus, the initial step in insulin action is unaltered in human obesity.", "contents": "Relation of insulin receptors to insulin resistance. The status of insulin-receptor interactions in a variety of insulin-resistant states is reviewed. Utilizing large adipocytes from adult rats and small fat cells from young rats, we have conducted a series of in vitro experiments in an attempt to determine the cellular alteration(s) responsible for the insulin resistance associated with obesity. Stimulation of glucose oxidation by insulin is reduced in large cells. Studies using a mimicker of insulin action, spermine, as well as measurements of 125I-insulin binding to large and small cells indicate that receptor number and affinity are not responsible for hormone resistance. Furthermore, when rapid and direct measurements of sugar uptake were made, insulin stimulation was virtually identical in both cell types. These findings indicate that large adipocytes have an efficient insulin-responsive D-glucose transport system and suggest that the apparent hormone resistance may be due to alterations in intracellular glucose metabolism. It has been proposed that altered insulin-receptor interaction underlies the insulin resistance of human obesity. We have investigated this particular aspect of insulin action by 125I-insulin binding studies. Similar numbers of insulin receptors per cell and affinity for insulin were observed in adipocytes obtained from normal weight subjects and morbidly obese patients. Thus, the initial step in insulin action is unaltered in human obesity."} {"id": "PMID:165986", "title": "[Classical and current aspects of the formation of motor dominance in man].", "content": "In the paper, significance of driving phenomenon for formation of motor dominant is considered and experimentally corroborated with the aid of autocorrelation and spectral analysis of the working man's EEG. The A.A. Ukhtomsky classical postulate has been complemented by contemporary ideas of the role of phasic relationships between the cortical activity for extablishing intercentral interconnections and the functional differentiation of working and irrelevant cortical structures. Data of correlation, crosscorrelation, and coherent EEG analysis enable to ascertain stages of formation of motor dominants at the cortical level and to judge of possible mechanisms of concentration of the dominant consstellations, as well as to show significance of the coadjustment for a common rhythm and of coincidence in phase of oscillations for improvement of the effectiveness of motor activity in man.", "contents": "[Classical and current aspects of the formation of motor dominance in man]. In the paper, significance of driving phenomenon for formation of motor dominant is considered and experimentally corroborated with the aid of autocorrelation and spectral analysis of the working man's EEG. The A.A. Ukhtomsky classical postulate has been complemented by contemporary ideas of the role of phasic relationships between the cortical activity for extablishing intercentral interconnections and the functional differentiation of working and irrelevant cortical structures. Data of correlation, crosscorrelation, and coherent EEG analysis enable to ascertain stages of formation of motor dominants at the cortical level and to judge of possible mechanisms of concentration of the dominant consstellations, as well as to show significance of the coadjustment for a common rhythm and of coincidence in phase of oscillations for improvement of the effectiveness of motor activity in man."} {"id": "PMID:165987", "title": "[Work dominance and its age-related development].", "content": "When studying working industrial processes, peculiar displays of the dominant corresponding to common signs of the Ukhtomsky dominant, were revealed. Some physiological processes characteristic of the dominant were studied in their developing in children of different age and in adolescents.", "contents": "[Work dominance and its age-related development]. When studying working industrial processes, peculiar displays of the dominant corresponding to common signs of the Ukhtomsky dominant, were revealed. Some physiological processes characteristic of the dominant were studied in their developing in children of different age and in adolescents."} {"id": "PMID:165988", "title": "[Polygraphic study of sleep in dogs].", "content": "Phenomenology and structure of the dog sleep were studied in chronic experiments. Three stages of NREM and REM phases were revealed. Sleeep in the dog was shown to differ from sleep in the rat, rabbit, and cat by appearance of alpha-like regular rhythm 8--9/sec during the onset of drowsiness, and by the sigma-rhythm first appearing against the background of clear slow waves. The exact estimation of REM sleep was shown to need a combined consideration of the EEG data with one of the two other signs (EMG or EOG).", "contents": "[Polygraphic study of sleep in dogs]. Phenomenology and structure of the dog sleep were studied in chronic experiments. Three stages of NREM and REM phases were revealed. Sleeep in the dog was shown to differ from sleep in the rat, rabbit, and cat by appearance of alpha-like regular rhythm 8--9/sec during the onset of drowsiness, and by the sigma-rhythm first appearing against the background of clear slow waves. The exact estimation of REM sleep was shown to need a combined consideration of the EEG data with one of the two other signs (EMG or EOG)."} {"id": "PMID:166004", "title": "Gastric acid secretion and sleep stages during natural night sleep.", "content": "Gastric acid secretion during natural sleep was studied in 4 healthy female volunteers for 11 nights. Acid output was measured by means of intragastric titration and a telemetering capsule, and sleep was monitored continuously by recording EEG and eye movements. Compared to the waking state, sleep was found to be associated with significantly lower levels of acid secretion. Although there were no significant differences between acid secretion during sleep stages 1 to 4 and rapid eye movement (REM), acid secretion decreased with deeper stages of sleep. During all REM phases only small amounts of acid were produced. Arousal or periods of waking in the course of the night, as well as waking in the morning, were associated with an increase in acid output.", "contents": "Gastric acid secretion and sleep stages during natural night sleep. Gastric acid secretion during natural sleep was studied in 4 healthy female volunteers for 11 nights. Acid output was measured by means of intragastric titration and a telemetering capsule, and sleep was monitored continuously by recording EEG and eye movements. Compared to the waking state, sleep was found to be associated with significantly lower levels of acid secretion. Although there were no significant differences between acid secretion during sleep stages 1 to 4 and rapid eye movement (REM), acid secretion decreased with deeper stages of sleep. During all REM phases only small amounts of acid were produced. Arousal or periods of waking in the course of the night, as well as waking in the morning, were associated with an increase in acid output."} {"id": "PMID:166005", "title": "[The atypical vessels of the feminine breast in the plate-thermography (author's transl)].", "content": "In 215 atypical--including 109 carcinomas and 8 carcinomata in situ--as well as 294 verified benign histological evidences of the breast the value of the main clinical, mammographical and plate-thermographical symptoms is examined. The clinical palpable tumors, the mammographical irregular connective tissue and/or the homogenous opacity, as well as plate-thermographical atypical vessels proved to be a relatively insecure sign of a carcinoma. The individual characteristics of the atypical vessels in the plate-thermography according to Tricoire were worked out. The sudden and blunt breaking-off of a atypical vessel has to be considered the most suspicious sign for a carcinoma. The plate-thermography according to Tricoire is also usable as additive method for diagnosis of benign breast-tumors that don't have to be exstirpated.", "contents": "[The atypical vessels of the feminine breast in the plate-thermography (author's transl)]. In 215 atypical--including 109 carcinomas and 8 carcinomata in situ--as well as 294 verified benign histological evidences of the breast the value of the main clinical, mammographical and plate-thermographical symptoms is examined. The clinical palpable tumors, the mammographical irregular connective tissue and/or the homogenous opacity, as well as plate-thermographical atypical vessels proved to be a relatively insecure sign of a carcinoma. The individual characteristics of the atypical vessels in the plate-thermography according to Tricoire were worked out. The sudden and blunt breaking-off of a atypical vessel has to be considered the most suspicious sign for a carcinoma. The plate-thermography according to Tricoire is also usable as additive method for diagnosis of benign breast-tumors that don't have to be exstirpated."} {"id": "PMID:166019", "title": "Genetic control of radiation sensitivity in Schizosaccharomyces pombe.", "content": "Genetic analysis of a large number of radiation-sensitive mutants of S. pombe, isolated in different laboratories, showed that these isolates represent 22 non-allelic loci. The mutants were shown to fall into three distinct classes concerning response to UV and ionizing radiation, including two mutants which are primarily sensitive to ionizing radiation but not to UV. Single-gene mutants were crossed to obtain supersensitive double mutants. Such double mutants showed a marked increase in sensitivty to a variety of inactivating agents as compared to the parental strains. The isolation of three classes of radiation-sensitive mutants and the construction of double mutants implies the presence of multiple pathways in S. pombe for repair of radiation-induced damage. The bearing of these data on cellular repair mechanisms in eukaryotes is discussed.", "contents": "Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetic analysis of a large number of radiation-sensitive mutants of S. pombe, isolated in different laboratories, showed that these isolates represent 22 non-allelic loci. The mutants were shown to fall into three distinct classes concerning response to UV and ionizing radiation, including two mutants which are primarily sensitive to ionizing radiation but not to UV. Single-gene mutants were crossed to obtain supersensitive double mutants. Such double mutants showed a marked increase in sensitivty to a variety of inactivating agents as compared to the parental strains. The isolation of three classes of radiation-sensitive mutants and the construction of double mutants implies the presence of multiple pathways in S. pombe for repair of radiation-induced damage. The bearing of these data on cellular repair mechanisms in eukaryotes is discussed."} {"id": "PMID:166020", "title": "Complementation analysis of methyl methane-sulfonate-induced recessive lethal mutations in the zeste-white region of the X chromosome of Drosophila melanogaster.", "content": "Recessive lethan mutations in the 3A1 to 3C2 region of the X-chromosome of Drosophila melanogaster were detected in 113 of 33,544 sperm treated by feeding 5 mM methyl methanesulfonate in 1% sucrose for 22 hours. Seven of the 113 lethans were sterile, leaving 106 for analysis by complementation tests. With only one exception, these mutants were found to have lesions restricted to single loci. One of these single-site mutations was in qt, 2 in tko, 18 in zw-1, 12 in zw-8, 6 in zw-4, 3 in zw-10, 3 in zw-13, 21 in zw-2, 7 in zw-3, 5 in zw-6, 6 in zw-12, 1 in zw-7, 12 in zw-5, 5 in zw-11, and 3 in zw-9. One of the lethals, m69, was non-complementary to two adjacent loci, zw-2 and zw-3, possible indicating a deletion encompassing two loci. The results confirm that there are at least 15 recessive lethal loci in the region and are consistent with the hypothesis of LIM and SYNDER (1968 and 1974) that inability of monofunctional alkylating chemicals to induce deletion associated mutations is a characteristic of the compounds.", "contents": "Complementation analysis of methyl methane-sulfonate-induced recessive lethal mutations in the zeste-white region of the X chromosome of Drosophila melanogaster. Recessive lethan mutations in the 3A1 to 3C2 region of the X-chromosome of Drosophila melanogaster were detected in 113 of 33,544 sperm treated by feeding 5 mM methyl methanesulfonate in 1% sucrose for 22 hours. Seven of the 113 lethans were sterile, leaving 106 for analysis by complementation tests. With only one exception, these mutants were found to have lesions restricted to single loci. One of these single-site mutations was in qt, 2 in tko, 18 in zw-1, 12 in zw-8, 6 in zw-4, 3 in zw-10, 3 in zw-13, 21 in zw-2, 7 in zw-3, 5 in zw-6, 6 in zw-12, 1 in zw-7, 12 in zw-5, 5 in zw-11, and 3 in zw-9. One of the lethals, m69, was non-complementary to two adjacent loci, zw-2 and zw-3, possible indicating a deletion encompassing two loci. The results confirm that there are at least 15 recessive lethal loci in the region and are consistent with the hypothesis of LIM and SYNDER (1968 and 1974) that inability of monofunctional alkylating chemicals to induce deletion associated mutations is a characteristic of the compounds."} {"id": "PMID:166029", "title": "The determination of paraquat using thin-layer chromatography.", "content": "A thin-layer chromatographic method for the detection and determination of Paraquat in biological materials is presented. Paraquat was concentrated efficiently with the ion-exchange resin Dowex 50W-4 using a batch operation. Of the 16 solvent systems used the best results were obtained on silica gel G plates with methanol : 6N hydrochloric acid (20 : 30) or methanol : 6N sulfuric acid (20 : 30); and on cellulose plates with methanol : 6N hydrochloric acid (35 : 15) or methanol : 6N sulfuric acid (40 : 10). Also described is a microplate method for the thin-layer chromatography of Paraquat.", "contents": "The determination of paraquat using thin-layer chromatography. A thin-layer chromatographic method for the detection and determination of Paraquat in biological materials is presented. Paraquat was concentrated efficiently with the ion-exchange resin Dowex 50W-4 using a batch operation. Of the 16 solvent systems used the best results were obtained on silica gel G plates with methanol : 6N hydrochloric acid (20 : 30) or methanol : 6N sulfuric acid (20 : 30); and on cellulose plates with methanol : 6N hydrochloric acid (35 : 15) or methanol : 6N sulfuric acid (40 : 10). Also described is a microplate method for the thin-layer chromatography of Paraquat."} {"id": "PMID:166033", "title": "Multiple hormone producing islet cell carcinomas of the pancreas. A morphological and biochemical investigation.", "content": "Biochemical, light, and electron microscopic studies of two multiple hormone producing metastic islet cell carcinomas of the pancreas are presented. Both tumors initially produced symptoms referable to a single hormone and over a period of years produced two other endocrine active polypeptides. The tumor in case 1 had been studied electron microscopically six years previously and had demonstrated no significant ultrastructural changes since then. The tumor in case 2 contained secretory granules of markedly varying size and density, suggesting a formation of packaged precursor molecules of possibly all three hormones. The pathogenesis of these tumors is discussed in light of recent evidence concerning the origin of endocrine cells.", "contents": "Multiple hormone producing islet cell carcinomas of the pancreas. A morphological and biochemical investigation. Biochemical, light, and electron microscopic studies of two multiple hormone producing metastic islet cell carcinomas of the pancreas are presented. Both tumors initially produced symptoms referable to a single hormone and over a period of years produced two other endocrine active polypeptides. The tumor in case 1 had been studied electron microscopically six years previously and had demonstrated no significant ultrastructural changes since then. The tumor in case 2 contained secretory granules of markedly varying size and density, suggesting a formation of packaged precursor molecules of possibly all three hormones. The pathogenesis of these tumors is discussed in light of recent evidence concerning the origin of endocrine cells."} {"id": "PMID:166034", "title": "Histologic variants of infiltrating lobular carcinoma of the breast.", "content": "Thirty-eight breasts with lobular carcinoma in situ and an additional intraductal or infiltrating cancer were studied. Twenty-six of the additional cancers were diagnosed as infiltrating lobular cancer on the basis of a single population of small uniform cells cytologically identical to those in lobular carcinoma in situ. In 20 of these cases the conventional pattern of infiltrating lobular cancer was evident with an individual cell infiltrate with foci of single filing. In the other six there was a confluent arrangement of cells in solid sheets. This pattern has not been previously reported as a pattern of infiltrating lobular cancer. Because of the identical cytologic appearance, we believe it is a variant of infiltraing lobular cancer and should be diagnosed as such.", "contents": "Histologic variants of infiltrating lobular carcinoma of the breast. Thirty-eight breasts with lobular carcinoma in situ and an additional intraductal or infiltrating cancer were studied. Twenty-six of the additional cancers were diagnosed as infiltrating lobular cancer on the basis of a single population of small uniform cells cytologically identical to those in lobular carcinoma in situ. In 20 of these cases the conventional pattern of infiltrating lobular cancer was evident with an individual cell infiltrate with foci of single filing. In the other six there was a confluent arrangement of cells in solid sheets. This pattern has not been previously reported as a pattern of infiltrating lobular cancer. Because of the identical cytologic appearance, we believe it is a variant of infiltraing lobular cancer and should be diagnosed as such."} {"id": "PMID:166035", "title": "Studies on the immune response and pathogenesis of Sendai virus infection of mice. III. The effects of cyclophosphamide.", "content": "Studies of the effects of cyclophosphamide on a non-lethal primary Sendai virus infection of mice are reported. Treatment with cyclophosphamide resulted in failure to limit or eradicate virus, diminished and delayed the appearance of immunoglobulin-secreting cells in the lungs and the production of local and serum antibody, reduced and delayed the appearance of bronchial basement membrane damage and the desquamation of infected mucosal cells, and reduced the incidence of immune complex deposition in the kidneys. Evidence is presented which indicated that some escape from immunosuppression occured by day 6, resulting in local antibody production. The appearance of the local antibody response was associated with increased tissue damage in the lungs and the deposition of immune complexes of viral antigen and antibody in the kidney. Nine further experiments were performed in mice to investigate this renal manifestation and preliminary results are presented. In four of seven Sendai and one of two avirulent influenza A (Kunz) virus infections glomerular immune complexes were found. Studies in C3H and C57 B1 mice and their F1 hybrid suggested that genetic factors play some part in the renal findings. The results are discussed with respect to the possible beneficial and harmful effects of the immune response to trivial respiratory virus infections.", "contents": "Studies on the immune response and pathogenesis of Sendai virus infection of mice. III. The effects of cyclophosphamide. Studies of the effects of cyclophosphamide on a non-lethal primary Sendai virus infection of mice are reported. Treatment with cyclophosphamide resulted in failure to limit or eradicate virus, diminished and delayed the appearance of immunoglobulin-secreting cells in the lungs and the production of local and serum antibody, reduced and delayed the appearance of bronchial basement membrane damage and the desquamation of infected mucosal cells, and reduced the incidence of immune complex deposition in the kidneys. Evidence is presented which indicated that some escape from immunosuppression occured by day 6, resulting in local antibody production. The appearance of the local antibody response was associated with increased tissue damage in the lungs and the deposition of immune complexes of viral antigen and antibody in the kidney. Nine further experiments were performed in mice to investigate this renal manifestation and preliminary results are presented. In four of seven Sendai and one of two avirulent influenza A (Kunz) virus infections glomerular immune complexes were found. Studies in C3H and C57 B1 mice and their F1 hybrid suggested that genetic factors play some part in the renal findings. The results are discussed with respect to the possible beneficial and harmful effects of the immune response to trivial respiratory virus infections."} {"id": "PMID:166036", "title": "Immunodeficiency in the chicken. I. Disparity in suppression of antibody responses to various antigens following surgical bursectomy.", "content": "The extent of suppression of antibody response by bursectomy (Bx) was examined as a measure of the seeding sequence of different clones from the bursa to peripheral lymphoid tissues. Chickens were bursectomized surgically 1, 4 or 7 days after hatching and immunized later with four antigens: sheep red blood cells (SRBC); Bordetella pertussis (Bp); human serum albumin (HSA); influenza virus (IV). The kinetics of the antibody responses were delayed in bursectomized birds when compared with the control groups. The following order in the degree of immunosuppression was established: Bp greater than HSA greater than SRBC greater than IV. This is discussed in relation to the 'sequential maturation' theory of ontogenesis of immunocyte differentiation. The data also stress the limitation of non-specific markers for assessing partial immunodeficiency states.", "contents": "Immunodeficiency in the chicken. I. Disparity in suppression of antibody responses to various antigens following surgical bursectomy. The extent of suppression of antibody response by bursectomy (Bx) was examined as a measure of the seeding sequence of different clones from the bursa to peripheral lymphoid tissues. Chickens were bursectomized surgically 1, 4 or 7 days after hatching and immunized later with four antigens: sheep red blood cells (SRBC); Bordetella pertussis (Bp); human serum albumin (HSA); influenza virus (IV). The kinetics of the antibody responses were delayed in bursectomized birds when compared with the control groups. The following order in the degree of immunosuppression was established: Bp greater than HSA greater than SRBC greater than IV. This is discussed in relation to the 'sequential maturation' theory of ontogenesis of immunocyte differentiation. The data also stress the limitation of non-specific markers for assessing partial immunodeficiency states."} {"id": "PMID:166037", "title": "Immunodeficiency in the chicken. II. Production of monomeric IgM following testosterone treatment or infection with Gumboro disease.", "content": "Chickens were treated at an early embryonal age with testosterone propionate or infected neonatally with the virus producing Gumboro disease. Their sera were subsequently fractionated by Sephadex G-200 chromatography, and showed a complete deficiency of IgG and the presence of IgM which was eluted with the 7S protein fraction. Purified and 125-I-labelled monomeric IgM was examined by SDS-acrylamide gel electrophoresis and found to contain both mu and light chains, together with a chain of intermediary size, which was absent from the patterns of 19S IgM or IgG.", "contents": "Immunodeficiency in the chicken. II. Production of monomeric IgM following testosterone treatment or infection with Gumboro disease. Chickens were treated at an early embryonal age with testosterone propionate or infected neonatally with the virus producing Gumboro disease. Their sera were subsequently fractionated by Sephadex G-200 chromatography, and showed a complete deficiency of IgG and the presence of IgM which was eluted with the 7S protein fraction. Purified and 125-I-labelled monomeric IgM was examined by SDS-acrylamide gel electrophoresis and found to contain both mu and light chains, together with a chain of intermediary size, which was absent from the patterns of 19S IgM or IgG."} {"id": "PMID:166040", "title": "Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis.", "content": "Collagens from various vertebrate tissues were tested for their ability to consume complement (C) activity upon incubation in human serum or with isolated components of complement. 10 of 12 collagens tested had anticomplementary activity. The heat-denatured form of collagen, gelatin, was found weakly anticomplementary, but elastin was found inactive in the interaction with C. Inactivation of C is a reaction which is dependent on the time of incubation and the collagen concentration and partially dependent on the temperature of incubation. Most collagens depleted C from human serum in presence of cation chelators, EDTA and EGTA, whereas the large part of anticomplementary activity of soluble collagens obtained from rat skin was abolished in presence of EDTA. Evidence is presented that two different principles in collagens play a role in inactivation of C. A factor, contained in insoluble collagens and inhibitable by mild oxidation with periodate, inactivates C1 directly even in presence of chelating agents. Another principle, contained in soluble and insoluble collagen and resistant to periodate treatment, depletes C in serum by utilization of C via the alternate pathway (the C3 shunt).", "contents": "Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis. Collagens from various vertebrate tissues were tested for their ability to consume complement (C) activity upon incubation in human serum or with isolated components of complement. 10 of 12 collagens tested had anticomplementary activity. The heat-denatured form of collagen, gelatin, was found weakly anticomplementary, but elastin was found inactive in the interaction with C. Inactivation of C is a reaction which is dependent on the time of incubation and the collagen concentration and partially dependent on the temperature of incubation. Most collagens depleted C from human serum in presence of cation chelators, EDTA and EGTA, whereas the large part of anticomplementary activity of soluble collagens obtained from rat skin was abolished in presence of EDTA. Evidence is presented that two different principles in collagens play a role in inactivation of C. A factor, contained in insoluble collagens and inhibitable by mild oxidation with periodate, inactivates C1 directly even in presence of chelating agents. Another principle, contained in soluble and insoluble collagen and resistant to periodate treatment, depletes C in serum by utilization of C via the alternate pathway (the C3 shunt)."} {"id": "PMID:166041", "title": "Dreams and dementia: a laboratory exploration of dream recall and dream content in chronic brain syndrome patients.", "content": "Seventeen (seven mild and ten severe) chronic brain syndrome patients were testes in the sleep laboratory for dream recall and content. The mildly organic patients had 57 per cent recall while the severely organic patients had 35 per cent recall. We also studied four aged severely organic patients. These patients showed a recall rate of 8 per cent. The difference between the recall rates in mildly and severely organic middle-aged patients was not statistically significant. The difference between the recall rates of the aged severely organic patients and either or both of the middle-aged groups was statistically significant (p smaller than .001). In addition, we found dream content differences between the mildly and severely organic middle-aged groups and between the combined group and normal young men.", "contents": "Dreams and dementia: a laboratory exploration of dream recall and dream content in chronic brain syndrome patients. Seventeen (seven mild and ten severe) chronic brain syndrome patients were testes in the sleep laboratory for dream recall and content. The mildly organic patients had 57 per cent recall while the severely organic patients had 35 per cent recall. We also studied four aged severely organic patients. These patients showed a recall rate of 8 per cent. The difference between the recall rates in mildly and severely organic middle-aged patients was not statistically significant. The difference between the recall rates of the aged severely organic patients and either or both of the middle-aged groups was statistically significant (p smaller than .001). In addition, we found dream content differences between the mildly and severely organic middle-aged groups and between the combined group and normal young men."} {"id": "PMID:166042", "title": "Effects of ionizing radiation on dried spores of Osmunda regalis III. 35 GHz e.s.r. study.", "content": "The use of 35 GHz microwave frequency has greatly simplified the separation of overlapping signals in dried irradiated fern spores. While in general confirming the conclusions previously drawn from X-band spectra, the use of Q-band has clarified several assignments of radical groups and allowed the recognition of additional radical groups or sub-groups.", "contents": "Effects of ionizing radiation on dried spores of Osmunda regalis III. 35 GHz e.s.r. study. The use of 35 GHz microwave frequency has greatly simplified the separation of overlapping signals in dried irradiated fern spores. While in general confirming the conclusions previously drawn from X-band spectra, the use of Q-band has clarified several assignments of radical groups and allowed the recognition of additional radical groups or sub-groups."} {"id": "PMID:166043", "title": "Comparison of radiolysis products of thymine and thymidine with e.s.r. results.", "content": "Radicals determined by e.s.r. spectrometry of irradiated thymine or thymidine and radiolytic products generated under tha ction of gamma rays in aerated aqueous solutions have been compared. This comparison lies mainly in the fact that a radical R gives rapidly the corresponding peroxide ROOH. The authors have isolated and characterized twenty peroxides, i.e., the four isomers cis (-), cis (+), trans (-), trans(+) of 6-hydroperoxy-5-hydroxy-5,6-dihydrothymidine; the four isomers cis (-), cis (+), trans (-), trans (+) of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine; 5-hydroperoxy-2-deoxyuridin;cis and trans 6-hydroperoxy-5-hydroxy-5,6-dihydrothymine; cis and trans 5-hydroperoxy-6-hydroxy-5,6-dihydrothymine; 5-hydroperoxymethyl-uracil; 5-hydroperoxy-5,6-dihydrothymine;cis and trans 6-hydroperoxy-5,6-dihydrothymine; 5-hydroperoxy-5-methyl barbituric acid; 5-hydroperoxy-5-methyl hydantoin; trans 5,6-dihydroperoxy-5,6-dihydrothymine. Most of thethymine and thymidine radicals hypothesized or described in the literature were correlated to these peroxides. However, the presence of certain peroxides could not be explained by recognized radicals. Taking advantage of this fact, the existence of new thymine or thymidine radicals so far unknown can be predicted.", "contents": "Comparison of radiolysis products of thymine and thymidine with e.s.r. results. Radicals determined by e.s.r. spectrometry of irradiated thymine or thymidine and radiolytic products generated under tha ction of gamma rays in aerated aqueous solutions have been compared. This comparison lies mainly in the fact that a radical R gives rapidly the corresponding peroxide ROOH. The authors have isolated and characterized twenty peroxides, i.e., the four isomers cis (-), cis (+), trans (-), trans(+) of 6-hydroperoxy-5-hydroxy-5,6-dihydrothymidine; the four isomers cis (-), cis (+), trans (-), trans (+) of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine; 5-hydroperoxy-2-deoxyuridin;cis and trans 6-hydroperoxy-5-hydroxy-5,6-dihydrothymine; cis and trans 5-hydroperoxy-6-hydroxy-5,6-dihydrothymine; 5-hydroperoxymethyl-uracil; 5-hydroperoxy-5,6-dihydrothymine;cis and trans 6-hydroperoxy-5,6-dihydrothymine; 5-hydroperoxy-5-methyl barbituric acid; 5-hydroperoxy-5-methyl hydantoin; trans 5,6-dihydroperoxy-5,6-dihydrothymine. Most of thethymine and thymidine radicals hypothesized or described in the literature were correlated to these peroxides. However, the presence of certain peroxides could not be explained by recognized radicals. Taking advantage of this fact, the existence of new thymine or thymidine radicals so far unknown can be predicted."} {"id": "PMID:166048", "title": "Muscle fiber and motor end plate involvement in the extraocular muscles of the myotonic mouse.", "content": "The extraocular muscles of the C57BL/6Jdy-2j myotonic mouse were studied by phase and electron microscopy. The most susceptible ocular muscle was the levator palpebrae; the other muscles manifested scattered abnormalities to varying degrees. Central nucleation and fiber splitting were prominent. Junctional abnormalities consisted of a reduction in post-junctional folding, excessive numbers of axonal terminals on hypertrophic fibers, and the presence of dense granules between axon and muscle. This study demonstrates the affection of both muscle fiber and motor end plate in mouse myotonic dystrophy.", "contents": "Muscle fiber and motor end plate involvement in the extraocular muscles of the myotonic mouse. The extraocular muscles of the C57BL/6Jdy-2j myotonic mouse were studied by phase and electron microscopy. The most susceptible ocular muscle was the levator palpebrae; the other muscles manifested scattered abnormalities to varying degrees. Central nucleation and fiber splitting were prominent. Junctional abnormalities consisted of a reduction in post-junctional folding, excessive numbers of axonal terminals on hypertrophic fibers, and the presence of dense granules between axon and muscle. This study demonstrates the affection of both muscle fiber and motor end plate in mouse myotonic dystrophy."} {"id": "PMID:166049", "title": "Mucolipidosis IV: ocular, systemic, and ultrastructural findings.", "content": "The ocular and systemic findings in four children with mucolipidosis IV (ML IV), a new variant of mucolipidosis, are described. Corneal clouding from birth or early infancy is a prominent feature in all of the patients and in two of them, this was the presenting symptom. Psychomotor retardation usually does not become apparent until the end of the first year of life. Conjunctival biopsies revealed two types of abnormal inclusion bodies: (1) single-membrane-limited cytoplasmic vacuoles containing both fibrillogranular material and membranous lamellae, and (2) lamellar and concentric bodies similar to those found in Tay-Sachs disease. The abnormal cytoplasmic organelles were present in both the stromal fibroblasts and the epithelial cells. The electroretrinogram performed in one patient was subnormal.", "contents": "Mucolipidosis IV: ocular, systemic, and ultrastructural findings. The ocular and systemic findings in four children with mucolipidosis IV (ML IV), a new variant of mucolipidosis, are described. Corneal clouding from birth or early infancy is a prominent feature in all of the patients and in two of them, this was the presenting symptom. Psychomotor retardation usually does not become apparent until the end of the first year of life. Conjunctival biopsies revealed two types of abnormal inclusion bodies: (1) single-membrane-limited cytoplasmic vacuoles containing both fibrillogranular material and membranous lamellae, and (2) lamellar and concentric bodies similar to those found in Tay-Sachs disease. The abnormal cytoplasmic organelles were present in both the stromal fibroblasts and the epithelial cells. The electroretrinogram performed in one patient was subnormal."} {"id": "PMID:166050", "title": "Cytologic changes of the retina and pigment epithelium during hibernation.", "content": "The pigment epithelium and the retina of hibernating frogs, bats, and ground squirrels are studied electron microscopically and the findings are compared with those of the same animals obtained in normal condition. The smooth endoplasmic reticulum of the pigment epithelial cell becomes sparse and transforms into large tubular structures during the hibernation. No appreciable changes are noted in the rod outer segments of hibernating bats and frogs. However, the cone outer segments of the ground squirrel show striking disappearance during experimental hibernation. Regeneration of the cone outer segments of the squirrel retina is found to be fast when the animals are placed in a normal environment.", "contents": "Cytologic changes of the retina and pigment epithelium during hibernation. The pigment epithelium and the retina of hibernating frogs, bats, and ground squirrels are studied electron microscopically and the findings are compared with those of the same animals obtained in normal condition. The smooth endoplasmic reticulum of the pigment epithelial cell becomes sparse and transforms into large tubular structures during the hibernation. No appreciable changes are noted in the rod outer segments of hibernating bats and frogs. However, the cone outer segments of the ground squirrel show striking disappearance during experimental hibernation. Regeneration of the cone outer segments of the squirrel retina is found to be fast when the animals are placed in a normal environment."} {"id": "PMID:166051", "title": "The effect of nonspecific immune stimulation on the recurrence rate of herpetic keratitis in rabbits.", "content": "Cellular immunity is of primary importance in resistance to virus infection. In this study, 75 rabbits were immunized with live BCG, 75 rabbits were immunized with Staphylococcus aureus, and 75 rabbits were injected with saline. Two weeks after immunization the corneal epithelium of both eyes was infected with McKrae strain herpes virus, and five weeks after immunization the rabbits were skin tested with old tuberculin or staphylococcus to ascertain their immune status. The corneas were observed under the slit lamp for recurrent epithelial herpes from day 52 through day 84 after immunization. During the second week of observation the group immunized with BCG had statistically significantly fewer recurrences than the saline-injected control group. The data for the BCG group during the remainder of the observation period, and for the SPL immunized group, were not statistically distinguishable from the control group. These experiments indicate that nonspecific immune stimulation provides little protection against recurrent herpetic infection. It is possible that manipulation of dosage and timing could enhance this effect.", "contents": "The effect of nonspecific immune stimulation on the recurrence rate of herpetic keratitis in rabbits. Cellular immunity is of primary importance in resistance to virus infection. In this study, 75 rabbits were immunized with live BCG, 75 rabbits were immunized with Staphylococcus aureus, and 75 rabbits were injected with saline. Two weeks after immunization the corneal epithelium of both eyes was infected with McKrae strain herpes virus, and five weeks after immunization the rabbits were skin tested with old tuberculin or staphylococcus to ascertain their immune status. The corneas were observed under the slit lamp for recurrent epithelial herpes from day 52 through day 84 after immunization. During the second week of observation the group immunized with BCG had statistically significantly fewer recurrences than the saline-injected control group. The data for the BCG group during the remainder of the observation period, and for the SPL immunized group, were not statistically distinguishable from the control group. These experiments indicate that nonspecific immune stimulation provides little protection against recurrent herpetic infection. It is possible that manipulation of dosage and timing could enhance this effect."} {"id": "PMID:166052", "title": "Experimental cerebral vasospasm and cyclic adenosine monophosphate (c-AMP).", "content": "Blood induced acute and chronic cerebral vasospasm were studied in Rhesus monkeys by serial angiography. Two vasoactive agents were evaluated. In acute spasm, phosphodiesterase inhibition by Aminophylline consistently reversed the vasospasm. This agent alone was ineffective in chronic spasm and required the addition of Isoproterenol to produce reversal of vasospasm. It is proposed that cerebral vasospasm may be associated with a decrease of intracellular c-AMP in vascular smooth muscle which can be reversed by manipulation of the enzyme pathway involved. It is further proposed that c-AMP is a basic common pathway through which adrenergic vascular reactivities are mediated.", "contents": "Experimental cerebral vasospasm and cyclic adenosine monophosphate (c-AMP). Blood induced acute and chronic cerebral vasospasm were studied in Rhesus monkeys by serial angiography. Two vasoactive agents were evaluated. In acute spasm, phosphodiesterase inhibition by Aminophylline consistently reversed the vasospasm. This agent alone was ineffective in chronic spasm and required the addition of Isoproterenol to produce reversal of vasospasm. It is proposed that cerebral vasospasm may be associated with a decrease of intracellular c-AMP in vascular smooth muscle which can be reversed by manipulation of the enzyme pathway involved. It is further proposed that c-AMP is a basic common pathway through which adrenergic vascular reactivities are mediated."} {"id": "PMID:166057", "title": "Lipids and lipoproteins in normal dogs and in dogs with secondary hyperlipoproteinemia.", "content": "Concentrations of serum cholesterol, triglyceride, and free glycerol were neasured, and serum lipoprotein electrophoresis was performed in normal dogs and in dogs with hypothyroidism, diabetes mellitus, and acute pancreatitis. Twelve privately owned dogs and 20 Basset Hounds from a research colony served as normal subjects. Privately owned had higher serum lipid concentrations than did research dogs. On electrophorisis of normal dog serum, lipoprotein bands were detected at the beta, pre-beta, alpha-2, and alpha-1 positions. Hypercholesterolemia was associated with increased intensity of the alpha-2-lipoprotein band, and hypertriglyceridemia occurred with increased lipoprotein at the origin, or the beta or pre-beta positions. Hypothyroid dogs had normal lipid values and lipoprotein electrophoretic patterns, hypercholesterolemia with increased intensity of the alpha-2-lipoprotein band, or hypercholesterolemia and hypertiglyceridemia with prominent beta-, pre-beta, and alpha-2-lipoprotein electrophoretic patterns were changed to near-normal values after levothyroxine administration. Diabetic dogs had increased serum cholesterol and triglyceride content and a predominance of lower density lipoproteins, as detected by electrophoresis. Insulin therapy caused the lipid concentrations to decrease and the electrophoretic pattern to revert to near normal. Dogs with acute pancreatitis had moderately increased serum lipid content and electrophoretic patterns characterized by increased intensity of the beta-lipoprotein band and by altered migration of alpha-1-lipoproteins.", "contents": "Lipids and lipoproteins in normal dogs and in dogs with secondary hyperlipoproteinemia. Concentrations of serum cholesterol, triglyceride, and free glycerol were neasured, and serum lipoprotein electrophoresis was performed in normal dogs and in dogs with hypothyroidism, diabetes mellitus, and acute pancreatitis. Twelve privately owned dogs and 20 Basset Hounds from a research colony served as normal subjects. Privately owned had higher serum lipid concentrations than did research dogs. On electrophorisis of normal dog serum, lipoprotein bands were detected at the beta, pre-beta, alpha-2, and alpha-1 positions. Hypercholesterolemia was associated with increased intensity of the alpha-2-lipoprotein band, and hypertriglyceridemia occurred with increased lipoprotein at the origin, or the beta or pre-beta positions. Hypothyroid dogs had normal lipid values and lipoprotein electrophoretic patterns, hypercholesterolemia with increased intensity of the alpha-2-lipoprotein band, or hypercholesterolemia and hypertiglyceridemia with prominent beta-, pre-beta, and alpha-2-lipoprotein electrophoretic patterns were changed to near-normal values after levothyroxine administration. Diabetic dogs had increased serum cholesterol and triglyceride content and a predominance of lower density lipoproteins, as detected by electrophoresis. Insulin therapy caused the lipid concentrations to decrease and the electrophoretic pattern to revert to near normal. Dogs with acute pancreatitis had moderately increased serum lipid content and electrophoretic patterns characterized by increased intensity of the beta-lipoprotein band and by altered migration of alpha-1-lipoproteins."} {"id": "PMID:166053", "title": "New diagnostic approach to brain lesions in nuclear medicine. Differential diagnosis of brain lesions with a computed brain scan diagnosis by the likelihood method.", "content": "Using 240 true positive brain scans, a computer system for the differential diagnosis of brain lesions has been evaluated. Eighty-six parameters were extracted from brain scan findings without relationship to neurological signs and symptoms, and the likelihood method was adopted as an example of mathematical logic. The results of our experiment indicated that the overall accuracy was 77 per cent for the maximum likelihood method. The digital computer gave satisfactory results, particularly for diseases such as infarct, meningioma, acoustic neurinoma, and subdural hematoma. In spite of several problems to be solved, this method could provide invaluable help in differential diagnosis of brain lesions.", "contents": "New diagnostic approach to brain lesions in nuclear medicine. Differential diagnosis of brain lesions with a computed brain scan diagnosis by the likelihood method. Using 240 true positive brain scans, a computer system for the differential diagnosis of brain lesions has been evaluated. Eighty-six parameters were extracted from brain scan findings without relationship to neurological signs and symptoms, and the likelihood method was adopted as an example of mathematical logic. The results of our experiment indicated that the overall accuracy was 77 per cent for the maximum likelihood method. The digital computer gave satisfactory results, particularly for diseases such as infarct, meningioma, acoustic neurinoma, and subdural hematoma. In spite of several problems to be solved, this method could provide invaluable help in differential diagnosis of brain lesions."} {"id": "PMID:166054", "title": "Survival factors following myocardial infarction recorded by a nurse.", "content": "Sixty-five patients were followed closely by a public health nurse following coronary-care unit discharge. A clear-cut pattern was observed in which nonsurvivors had increasing objective signs of physical deterioration and more hospital admissions, but verbalized fewer complaints than survivors. The differences between the eight nonsurvivors and the survivors were significant at the 0.05 level for the observed findings. These findings have implications for organizing health-care delivery.", "contents": "Survival factors following myocardial infarction recorded by a nurse. Sixty-five patients were followed closely by a public health nurse following coronary-care unit discharge. A clear-cut pattern was observed in which nonsurvivors had increasing objective signs of physical deterioration and more hospital admissions, but verbalized fewer complaints than survivors. The differences between the eight nonsurvivors and the survivors were significant at the 0.05 level for the observed findings. These findings have implications for organizing health-care delivery."} {"id": "PMID:166059", "title": "Adenovirus infection in two calves.", "content": "Two 2-week-old calves with pyrexia, diarrhea, and subsequent dehydration were treated symptomatically for 1 week, but without favorable response. At necropsy, foci of necrosis were found in the abomasum and rumen of each calf. The small and large intestineswere dilated by grayish, turbid fluid. Numerous large amphophilic, intranuclear inclusions in endothelial cells of blood vessels in the abomasum and rumen, in endothelial cellsof the adrenal cortical sinusoids and renal glomeruli, and in intestinal epithelial cells were identified as adenovirus particles.", "contents": "Adenovirus infection in two calves. Two 2-week-old calves with pyrexia, diarrhea, and subsequent dehydration were treated symptomatically for 1 week, but without favorable response. At necropsy, foci of necrosis were found in the abomasum and rumen of each calf. The small and large intestineswere dilated by grayish, turbid fluid. Numerous large amphophilic, intranuclear inclusions in endothelial cells of blood vessels in the abomasum and rumen, in endothelial cellsof the adrenal cortical sinusoids and renal glomeruli, and in intestinal epithelial cells were identified as adenovirus particles."} {"id": "PMID:166060", "title": "Survey for antibodies to leukemia (C-type) virus in cattle.", "content": "Serums from 4,394 dairy cattle in 100 herds and from 2,794 beef cattle in 50 herds were tested for antibody to the bovine (C-type) leukemia virus (BLV), using the agar gel immunodiffusion test. Reactors were found in 66% of the dairy herds (10.2% of the cattle) and in 14% of the beef herds (1.2% of the cattle). The prevalence of reactors was examined with respect to age, herd size, and sex. Few of the reactors were less than 2 years old. There was a high percentage of reactors in small dairy herds (less than 50 cattle). In 22 dairy herds (1,354 cows and 96 bulls), the rate of infection in cows was compared with that in bulls. In those herds, 13.5% of the cows and 10.4% of the bulls were reactors.", "contents": "Survey for antibodies to leukemia (C-type) virus in cattle. Serums from 4,394 dairy cattle in 100 herds and from 2,794 beef cattle in 50 herds were tested for antibody to the bovine (C-type) leukemia virus (BLV), using the agar gel immunodiffusion test. Reactors were found in 66% of the dairy herds (10.2% of the cattle) and in 14% of the beef herds (1.2% of the cattle). The prevalence of reactors was examined with respect to age, herd size, and sex. Few of the reactors were less than 2 years old. There was a high percentage of reactors in small dairy herds (less than 50 cattle). In 22 dairy herds (1,354 cows and 96 bulls), the rate of infection in cows was compared with that in bulls. In those herds, 13.5% of the cows and 10.4% of the bulls were reactors."} {"id": "PMID:166061", "title": "Effects of 5-fluorouracil on exocrine glands. III. Fine structure of Brunner's glands of rats.", "content": "Effects of a pyrimidine analogue, 5-fluorouracil (Fur), have been studied by electron microscopy and by electron microscopic cytochemical techniques. Previous studies have demonstrated that rats show serious gastrointestinal disturbances 5 days after 3 daily injections of FUR (50 mg/kg). The present investigation demonstrates that Brunner's glands under the same conditions suffer certain cytological changes involving the Golgi apparatus, where a notable reduction in the number of Golgi stacks is observed. The vacuolar components in the Golgi complex appear empty. Cytochemical localizations of uridine diphosphatase and thiamine pyrophosphatase activities, however, are normal. The reaction products are localized in the distal two or three lamellae of the Golgi stack and within the secretory granules nearby. In addition reaction products are present along the apical plasma membrane on the luminal side, suggesting a possible movement of these membranes from the Golgi stack, via secretory granules, to the apical plasma membrane.", "contents": "Effects of 5-fluorouracil on exocrine glands. III. Fine structure of Brunner's glands of rats. Effects of a pyrimidine analogue, 5-fluorouracil (Fur), have been studied by electron microscopy and by electron microscopic cytochemical techniques. Previous studies have demonstrated that rats show serious gastrointestinal disturbances 5 days after 3 daily injections of FUR (50 mg/kg). The present investigation demonstrates that Brunner's glands under the same conditions suffer certain cytological changes involving the Golgi apparatus, where a notable reduction in the number of Golgi stacks is observed. The vacuolar components in the Golgi complex appear empty. Cytochemical localizations of uridine diphosphatase and thiamine pyrophosphatase activities, however, are normal. The reaction products are localized in the distal two or three lamellae of the Golgi stack and within the secretory granules nearby. In addition reaction products are present along the apical plasma membrane on the luminal side, suggesting a possible movement of these membranes from the Golgi stack, via secretory granules, to the apical plasma membrane."} {"id": "PMID:166062", "title": "Ultrastructure of the submucous nerves of the rat ureter.", "content": "The fine structure and distribution of the nerves in the submucosa of the middle part of the ureter were studied in the adult rat. As in the rabbit, the nerves were concentrated on the inner surface of the muscle and beneath the epithelium. The nerves beneath the epithelium were smaller than those on the surface of the muscle, but they were much more numerous. They gave off small branches which ran for only short distances in the subepithelial connective tissue before terminating. Axonal varicosities were common and almost all appeared to represent the terminals of a single type of axon. The varicosities contained clusters of clear vesicles and variable numbers of larger dense-cored vesicles. The dense-cored vesicles were unaffected by short-term treatment with 6-OHDA and in this and other respects compared well with those of the terminals classified by Burnstock (1972) as purinergic. The possibility that the axons are sensory, and are the source of impulses which are recognized as being painful in nature, is discussed.", "contents": "Ultrastructure of the submucous nerves of the rat ureter. The fine structure and distribution of the nerves in the submucosa of the middle part of the ureter were studied in the adult rat. As in the rabbit, the nerves were concentrated on the inner surface of the muscle and beneath the epithelium. The nerves beneath the epithelium were smaller than those on the surface of the muscle, but they were much more numerous. They gave off small branches which ran for only short distances in the subepithelial connective tissue before terminating. Axonal varicosities were common and almost all appeared to represent the terminals of a single type of axon. The varicosities contained clusters of clear vesicles and variable numbers of larger dense-cored vesicles. The dense-cored vesicles were unaffected by short-term treatment with 6-OHDA and in this and other respects compared well with those of the terminals classified by Burnstock (1972) as purinergic. The possibility that the axons are sensory, and are the source of impulses which are recognized as being painful in nature, is discussed."} {"id": "PMID:166063", "title": "Observations on the structure of the dorsal muscle in the bottle-nose dolphin (Tursiops truncatus).", "content": "The dorsal muscle of five South Australian bottle-nose dolphins has been studied. The ultrastructure and cytochemistry of the red, white and intermediate fibres were essentially similar to those of other mammalian skeletal muscles. Two features of special interest were: (a) the large number of lipid droplets in the red muscle fibres, and (b) the presence of longitudinal tubes linking the transverse tubes of the T-system, both within a sarcomere, and also between adjacent sarcomeres, of the white muscle fibres. The muscle spindles and neuromuscular junctions in the dolphin appeared to be morphologically similar to those of other mammals.", "contents": "Observations on the structure of the dorsal muscle in the bottle-nose dolphin (Tursiops truncatus). The dorsal muscle of five South Australian bottle-nose dolphins has been studied. The ultrastructure and cytochemistry of the red, white and intermediate fibres were essentially similar to those of other mammalian skeletal muscles. Two features of special interest were: (a) the large number of lipid droplets in the red muscle fibres, and (b) the presence of longitudinal tubes linking the transverse tubes of the T-system, both within a sarcomere, and also between adjacent sarcomeres, of the white muscle fibres. The muscle spindles and neuromuscular junctions in the dolphin appeared to be morphologically similar to those of other mammals."} {"id": "PMID:166064", "title": "An electron microscopic study of the histogenesis of the parathyroid gland in the sheep.", "content": "Definitive chief cells, characterized by the presence of specific secretory granules and typical membrane configurations, were present in the developing parathyroid glands of sheep embryos from 26 days of gestation (term = 150 days). During earlier stages of gestation developing chief cells contained lysosomal systems which appeared to be concerned with the autophagy of retained secretion product. The EM evidence suggests that physiologic release of the hormone does not occur until at least 30 days of gestation, which correlates well with the experimentally established time of onset of functional capacity in the parathyroid gland in the sheep. 'Bark cells' were found in the parathyroid primordia of embryos between 20 and 27 days of gestation. The significance of these \"dark cells\" is discussed with respect to glutaraldehyde fixation and to their possible relationship to chief cells.", "contents": "An electron microscopic study of the histogenesis of the parathyroid gland in the sheep. Definitive chief cells, characterized by the presence of specific secretory granules and typical membrane configurations, were present in the developing parathyroid glands of sheep embryos from 26 days of gestation (term = 150 days). During earlier stages of gestation developing chief cells contained lysosomal systems which appeared to be concerned with the autophagy of retained secretion product. The EM evidence suggests that physiologic release of the hormone does not occur until at least 30 days of gestation, which correlates well with the experimentally established time of onset of functional capacity in the parathyroid gland in the sheep. 'Bark cells' were found in the parathyroid primordia of embryos between 20 and 27 days of gestation. The significance of these \"dark cells\" is discussed with respect to glutaraldehyde fixation and to their possible relationship to chief cells."} {"id": "PMID:166065", "title": "The ultrastructure of the sensory end-organs (baroreceptors) in the atrial endocardium of young mini-pigs.", "content": "Light and electron microscopical studies on pig hearts have confirmed the presence in the right and the left atrial endocardium of distinct circumscribed, unencapsulated end-organs (baroreceptors) associated with 4-9 mum thick nerve fibres. The myelin sheath terminates before the entrance of the nerve into the end-organ. The regular presence of thin axon profiles containing clusters of small agranular vesicles, both around the thick nerve fibre and in the periphery of the end-organs, suggests a double innervation. The thick fibre arborizes inside an aggregate of Schwann-like cells to form a large number of terminals which are considered to be the mechano-sensitive receptors of the organ. In addition to the nervous structures and the Schwann-like cells the organs contain a varying number of connective tissue fibrils. The terminals are covered by a basement membrane but are partly or completely devoid of Schwann cell covering. Most of the space inside the terminals is occupied by tightly packed mitochondria. Glycogen granules are regularly present, sometimes abundant. SER occurs widely, frequently forming complexes with glycogen granules. These complexes may be highly organized as parallel or concentric structures, suggesting a close connection between SER and glycogen metabolism in the terminals. The terminals are regularly furnished with small protrusions containing numerous 30-100 nm clear vesicles which resemble pinocytotic vesicles. In addition, a few 80 nm dense-cored vesicles are found. The occurrence of numerous cyto-segresomes and lipofuscin-like bodies suggests a lively turnover of organelles in the terminals.", "contents": "The ultrastructure of the sensory end-organs (baroreceptors) in the atrial endocardium of young mini-pigs. Light and electron microscopical studies on pig hearts have confirmed the presence in the right and the left atrial endocardium of distinct circumscribed, unencapsulated end-organs (baroreceptors) associated with 4-9 mum thick nerve fibres. The myelin sheath terminates before the entrance of the nerve into the end-organ. The regular presence of thin axon profiles containing clusters of small agranular vesicles, both around the thick nerve fibre and in the periphery of the end-organs, suggests a double innervation. The thick fibre arborizes inside an aggregate of Schwann-like cells to form a large number of terminals which are considered to be the mechano-sensitive receptors of the organ. In addition to the nervous structures and the Schwann-like cells the organs contain a varying number of connective tissue fibrils. The terminals are covered by a basement membrane but are partly or completely devoid of Schwann cell covering. Most of the space inside the terminals is occupied by tightly packed mitochondria. Glycogen granules are regularly present, sometimes abundant. SER occurs widely, frequently forming complexes with glycogen granules. These complexes may be highly organized as parallel or concentric structures, suggesting a close connection between SER and glycogen metabolism in the terminals. The terminals are regularly furnished with small protrusions containing numerous 30-100 nm clear vesicles which resemble pinocytotic vesicles. In addition, a few 80 nm dense-cored vesicles are found. The occurrence of numerous cyto-segresomes and lipofuscin-like bodies suggests a lively turnover of organelles in the terminals."} {"id": "PMID:166066", "title": "Ultrastructure of the blastocyst and endometrium of the roe deer (Capreolus capreolus) during delayed implantation.", "content": "Transmission electron microscopy of the trophoblast cells during diapause revealed an abundance of electron-dense, membrane-bound granular inclusions and a marked lack of cytoplasmic organelles. The cells also possessed a well-developed covering of branched microvilli, numerous caveolae, micropinocytotic vesicles and a lamina of fine fibrillae. The progressive enlargement of the blastocyst during diapause was correlated with a decline in the height of the trophoblast cells and a reduction in the density of microvilli and caveolae associated with the outer membrane. The granular inclusions also declined in number and electron density during the delay phase, suggesting the progressive utilisation of energy reserves. Embryonic elongation was associated with the disappearance of the granular inclusions, a reduction in the amount of fibrillar material and a dramatic increase in the development of cytoplasmic organelles. During diapause, clear vesicles, apparently derived from the Golgi apparatus, gradually accumulated in the supranuclear region of each gland and non-ciliated duct cell. Embryonic elongation was associated with the sudden release of these vesicles into the glandular lumen and thence into the uterine lumen. Numerous apical protrusions were also observed projecting from the luminal and ductal epithelia at this time, suggesting the formation of an apocrine secretion. Another type of secretion was produced during the early stages of placental attachment by the hypertrophied granular endoplasmic reticulum of the ductal epithelium.", "contents": "Ultrastructure of the blastocyst and endometrium of the roe deer (Capreolus capreolus) during delayed implantation. Transmission electron microscopy of the trophoblast cells during diapause revealed an abundance of electron-dense, membrane-bound granular inclusions and a marked lack of cytoplasmic organelles. The cells also possessed a well-developed covering of branched microvilli, numerous caveolae, micropinocytotic vesicles and a lamina of fine fibrillae. The progressive enlargement of the blastocyst during diapause was correlated with a decline in the height of the trophoblast cells and a reduction in the density of microvilli and caveolae associated with the outer membrane. The granular inclusions also declined in number and electron density during the delay phase, suggesting the progressive utilisation of energy reserves. Embryonic elongation was associated with the disappearance of the granular inclusions, a reduction in the amount of fibrillar material and a dramatic increase in the development of cytoplasmic organelles. During diapause, clear vesicles, apparently derived from the Golgi apparatus, gradually accumulated in the supranuclear region of each gland and non-ciliated duct cell. Embryonic elongation was associated with the sudden release of these vesicles into the glandular lumen and thence into the uterine lumen. Numerous apical protrusions were also observed projecting from the luminal and ductal epithelia at this time, suggesting the formation of an apocrine secretion. Another type of secretion was produced during the early stages of placental attachment by the hypertrophied granular endoplasmic reticulum of the ductal epithelium."} {"id": "PMID:166072", "title": "The crystal structure of bonito (katsuo) ferrocytochrome c at 2.3 A resolution. II. Structure and function.", "content": "The structure analysis of bonito heart ferrocytochrome c was carried out at 2.3 A resolution by X-ray diffraction, and a Kendrew-type skeletal model was built up. This molecule has an overall egg shape, 35 A in height, 30 A in width and 23 A in thickness; the 5th ligand of the heme iron atom is the N-epsilon atom of the His-18 imidazole ring and the 6th is the Met-80 sulfur atom. Distinct alpha-helix regions are found between the N-terminus and reside 11, between 60 and 69, and between 90 and the C-terminus. The most distinct difference between the conformation of the present molecule and that of the horse oxidized molecule is the location of the Phe-82 phenyl ring. In the present reduced molecule, the phyenyl ring is in closer contact with the iron atom and gives influences on the character of the iron atom. Inside the molecule, at the lower part of the heme pocket, there is an extended hydrogen bond network including the propionic acid residues of the heme group. Both Phe-82 and the hydrogen bond network may play a key role in the function of this molecule.", "contents": "The crystal structure of bonito (katsuo) ferrocytochrome c at 2.3 A resolution. II. Structure and function. The structure analysis of bonito heart ferrocytochrome c was carried out at 2.3 A resolution by X-ray diffraction, and a Kendrew-type skeletal model was built up. This molecule has an overall egg shape, 35 A in height, 30 A in width and 23 A in thickness; the 5th ligand of the heme iron atom is the N-epsilon atom of the His-18 imidazole ring and the 6th is the Met-80 sulfur atom. Distinct alpha-helix regions are found between the N-terminus and reside 11, between 60 and 69, and between 90 and the C-terminus. The most distinct difference between the conformation of the present molecule and that of the horse oxidized molecule is the location of the Phe-82 phenyl ring. In the present reduced molecule, the phyenyl ring is in closer contact with the iron atom and gives influences on the character of the iron atom. Inside the molecule, at the lower part of the heme pocket, there is an extended hydrogen bond network including the propionic acid residues of the heme group. Both Phe-82 and the hydrogen bond network may play a key role in the function of this molecule."} {"id": "PMID:166074", "title": "Dietary and hormonal regulation of serine synthesis in the rat.", "content": "The importance of the so-called phosphorylated pathway for the synthesis of serine in rat liver was confirmed by studies on in vitro serine synthesis and also by the existence of a correlation between the serine-synthesizing activity of liver extracts and the activities of the enzymes involved in the pathway under various dietary conditions. Serine-synthesizing activity was found to be distributed in various rat tissues such as kidney, brain, testis, spleen, pancreas, and fat pad. However, only in the liver was the synthesis regulated by dietary protein. In the liver, the three enzymes of the phosphorylated pathway were found to be repressed by high-protein diets or by starvation and induced by low-protein diets. The dietary induction of the enzymes required the presence of insulin and was suppressed by glucocorticoids. A suggestion is made that the effects of diet or hormones may be mediated by changes in the hepatic pool of essential amino acids.", "contents": "Dietary and hormonal regulation of serine synthesis in the rat. The importance of the so-called phosphorylated pathway for the synthesis of serine in rat liver was confirmed by studies on in vitro serine synthesis and also by the existence of a correlation between the serine-synthesizing activity of liver extracts and the activities of the enzymes involved in the pathway under various dietary conditions. Serine-synthesizing activity was found to be distributed in various rat tissues such as kidney, brain, testis, spleen, pancreas, and fat pad. However, only in the liver was the synthesis regulated by dietary protein. In the liver, the three enzymes of the phosphorylated pathway were found to be repressed by high-protein diets or by starvation and induced by low-protein diets. The dietary induction of the enzymes required the presence of insulin and was suppressed by glucocorticoids. A suggestion is made that the effects of diet or hormones may be mediated by changes in the hepatic pool of essential amino acids."} {"id": "PMID:166075", "title": "Studies on NADP-+-specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62.", "content": "1. NADP-+-specific isocitrate dehydrogenase [EC 1.1.1.42] was partially purified by about 440-fold from an extreme thermophile, Thermus flavus AT-62. 2. Remarkable thermostability of the enzyme was confirmed. The enzyme was not inactivated after 60 min at 70 degrees, and the activity was lost only slowly at 80 degrees. Above 90 degrees, however, rapid inactivation was observed. 3. The dehydrogenase was susceptible to concerted inhibition by oxaloacetate plus glyoxylate. In the presence of oxaloacetate plus glyoxylate (each 1 mM), 75 percent inhibition was observed. 4. The degree of inhibition of the enzyme by oxaloacetate plus glyoxylate decreased markedly above 60 degrees. The affinity of the enzyme for isocitrate and NADP-+ was also reduced markedly above 60 degrees. The activation energy calculated from Arrhenius plots below and above 60 degrees were 14,500 and 8,000 cal per mole, respectively. These observations suggest a possible conformation change of the enzyme protein at a transition temperature of 60 degrees, and the physiological significance of this in the adaptation of thermophiles to elevated temperatures is discussed.", "contents": "Studies on NADP-+-specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62. 1. NADP-+-specific isocitrate dehydrogenase [EC 1.1.1.42] was partially purified by about 440-fold from an extreme thermophile, Thermus flavus AT-62. 2. Remarkable thermostability of the enzyme was confirmed. The enzyme was not inactivated after 60 min at 70 degrees, and the activity was lost only slowly at 80 degrees. Above 90 degrees, however, rapid inactivation was observed. 3. The dehydrogenase was susceptible to concerted inhibition by oxaloacetate plus glyoxylate. In the presence of oxaloacetate plus glyoxylate (each 1 mM), 75 percent inhibition was observed. 4. The degree of inhibition of the enzyme by oxaloacetate plus glyoxylate decreased markedly above 60 degrees. The affinity of the enzyme for isocitrate and NADP-+ was also reduced markedly above 60 degrees. The activation energy calculated from Arrhenius plots below and above 60 degrees were 14,500 and 8,000 cal per mole, respectively. These observations suggest a possible conformation change of the enzyme protein at a transition temperature of 60 degrees, and the physiological significance of this in the adaptation of thermophiles to elevated temperatures is discussed."} {"id": "PMID:166079", "title": "Protein and glycoprotein electrophoretic patterns of enriched fractions of primary and secondary granules from guinea pig polymorphonuclear leukocytes.", "content": "The postnuclear supernatant fraction of sucrose homogenates of guinea pig polymorphonuclear leukocytes (PMNL) was subjected to differential centrifugation to obtain a total particulate fraction, a particle-free supernatant fraction, highly enriched fractions of primary and secondary granules, and a membrane-rich fraction. The various fractions were solubilized in buffer containing sodium dodecyl sulfate (SDS) and analyzed for protein and glycoproteincomponents by SDS -polyacrylamide gel electrophoresis. The major glycoprotein components of the postnuclear supernatant fraction were found mainly associated with the enriched fraction of secondary granules and, to a lesser extent, with the membrane-rich fraction. No major glycoprotein components were visible in the polypeptide electrophoretic patterns of the primary granule fraction or of the particle-free supernate. Attempts at separation of guinea pig granules by zonal sucrose density gradient centrifugation were only partially successful. Data supporting a species difference in this regard between rabbit and guinea pig PMNL granules are presented.", "contents": "Protein and glycoprotein electrophoretic patterns of enriched fractions of primary and secondary granules from guinea pig polymorphonuclear leukocytes. The postnuclear supernatant fraction of sucrose homogenates of guinea pig polymorphonuclear leukocytes (PMNL) was subjected to differential centrifugation to obtain a total particulate fraction, a particle-free supernatant fraction, highly enriched fractions of primary and secondary granules, and a membrane-rich fraction. The various fractions were solubilized in buffer containing sodium dodecyl sulfate (SDS) and analyzed for protein and glycoproteincomponents by SDS -polyacrylamide gel electrophoresis. The major glycoprotein components of the postnuclear supernatant fraction were found mainly associated with the enriched fraction of secondary granules and, to a lesser extent, with the membrane-rich fraction. No major glycoprotein components were visible in the polypeptide electrophoretic patterns of the primary granule fraction or of the particle-free supernate. Attempts at separation of guinea pig granules by zonal sucrose density gradient centrifugation were only partially successful. Data supporting a species difference in this regard between rabbit and guinea pig PMNL granules are presented."} {"id": "PMID:166085", "title": "Separation of tetracyclines by high-speed liquid chromatography.", "content": "The separation of tetracycline and its four commoninpurities has been studied by high-speed liquid chromatography. A preliminary study of the effectiveness of ion-exchange, adsorption, liquid-liquid partition and reversed-phase ion-pair chromatography indicated that only the last method showed promise. By developing special hydrocarbon-bonded stationary phases a rapid and complete resolution of all five tetracyclines has been obtained within 10 min. Plate heights using a derivatised 18-mum partisil are in the range 0.15-0.3 mm. The method can be used to quantify the impurities in tetracycline at around the 1% level.", "contents": "Separation of tetracyclines by high-speed liquid chromatography. The separation of tetracycline and its four commoninpurities has been studied by high-speed liquid chromatography. A preliminary study of the effectiveness of ion-exchange, adsorption, liquid-liquid partition and reversed-phase ion-pair chromatography indicated that only the last method showed promise. By developing special hydrocarbon-bonded stationary phases a rapid and complete resolution of all five tetracyclines has been obtained within 10 min. Plate heights using a derivatised 18-mum partisil are in the range 0.15-0.3 mm. The method can be used to quantify the impurities in tetracycline at around the 1% level."} {"id": "PMID:166086", "title": "Preparation and thin-layer chromatography of bromo-derivatives of unsaturated fatty acid esters. A simple and rapid procedure for fatty acid analysis.", "content": "Bromo-addition products of unsaturated long-chain fatty acid esters have been prepared and chromatographed on thin layers of unmodified silica gel. The polarity of these derivatives was found to be directly related to the number of double bonds of the parent fatty acid from which they were derived. This has been made the basis of a simple method for assessing the relative proportions of the main fatty acid classes in a mixture.", "contents": "Preparation and thin-layer chromatography of bromo-derivatives of unsaturated fatty acid esters. A simple and rapid procedure for fatty acid analysis. Bromo-addition products of unsaturated long-chain fatty acid esters have been prepared and chromatographed on thin layers of unmodified silica gel. The polarity of these derivatives was found to be directly related to the number of double bonds of the parent fatty acid from which they were derived. This has been made the basis of a simple method for assessing the relative proportions of the main fatty acid classes in a mixture."} {"id": "PMID:166087", "title": "Occurrence of big renin in human plasma, amniotic fluid and kidney extracts.", "content": "Big renin, a relatively inactive renin which possesses a molecular weight larger than that of normal plasma or renal renin, has been demonstrated by gel filtration in certain human plasma, tumor extracts, and amniotic fluid. Big renin was not present in normal plasma or kidney extracts. Plasma from 3 hypertensive patients with nephropathy contained chiefly big renin. Varying proportions of both big and normal renin activity were present in plasma of other patients with hypertension and proteinuria. The renin present in amniotic fluid, which increased in activity following exposure to acid pH, was shown to be big renin in two patients. Large amounts of circulating big renin apparently can cause hypertension in patients with Wilms' tumors. Furthermore, the relatively inactive big renin may replace normal plasma renin in some patients, resulting in low plasma renin activity.", "contents": "Occurrence of big renin in human plasma, amniotic fluid and kidney extracts. Big renin, a relatively inactive renin which possesses a molecular weight larger than that of normal plasma or renal renin, has been demonstrated by gel filtration in certain human plasma, tumor extracts, and amniotic fluid. Big renin was not present in normal plasma or kidney extracts. Plasma from 3 hypertensive patients with nephropathy contained chiefly big renin. Varying proportions of both big and normal renin activity were present in plasma of other patients with hypertension and proteinuria. The renin present in amniotic fluid, which increased in activity following exposure to acid pH, was shown to be big renin in two patients. Large amounts of circulating big renin apparently can cause hypertension in patients with Wilms' tumors. Furthermore, the relatively inactive big renin may replace normal plasma renin in some patients, resulting in low plasma renin activity."} {"id": "PMID:166088", "title": "Failure of somatostatin to inhibit tolbutamide-induced insulin secretion in patients with insulinomas: a possible diagnostic tool.", "content": "The effects of somatostatin on tolbutamide-stimulated insulin release were studied in 4 patients with insulin-producing tumors of the pancreas and in 6 normal subjects. In contrast to its effective inhibition of insulin release in normal subjects, somatostatin, without exception, failed to inhibit tolbutamide-induced insulin release in the patients with pancreatic beta-cell tumors. This differential effect of somatostatin may prove useful in the diagnosis of insulin-producing tumors of the pancreas.", "contents": "Failure of somatostatin to inhibit tolbutamide-induced insulin secretion in patients with insulinomas: a possible diagnostic tool. The effects of somatostatin on tolbutamide-stimulated insulin release were studied in 4 patients with insulin-producing tumors of the pancreas and in 6 normal subjects. In contrast to its effective inhibition of insulin release in normal subjects, somatostatin, without exception, failed to inhibit tolbutamide-induced insulin release in the patients with pancreatic beta-cell tumors. This differential effect of somatostatin may prove useful in the diagnosis of insulin-producing tumors of the pancreas."} {"id": "PMID:166089", "title": "Inhibition by somatostatin of ACTH secretion in Nelson's syndrome.", "content": "Somatostatin (GHIF), when administered as a 1-hr infusion (500 mug/hr) to 5 patients with Nelson's Syndrome;resulted in a sustained, progressive fall in plasma ACTH in each patient to 40% to 71% of basal values with a return toward initail levels after cessation of the infusion. The meanreduction in plasma ADTH was 48% (p less than 0.005). These finding suggest that GHIF receptors not fuctional or present in normal pituitary tissue are present in ACTH-producing pituitary tumors.", "contents": "Inhibition by somatostatin of ACTH secretion in Nelson's syndrome. Somatostatin (GHIF), when administered as a 1-hr infusion (500 mug/hr) to 5 patients with Nelson's Syndrome;resulted in a sustained, progressive fall in plasma ACTH in each patient to 40% to 71% of basal values with a return toward initail levels after cessation of the infusion. The meanreduction in plasma ADTH was 48% (p less than 0.005). These finding suggest that GHIF receptors not fuctional or present in normal pituitary tissue are present in ACTH-producing pituitary tumors."} {"id": "PMID:166090", "title": "Effects of sodium depletion on plasma renin activity and on the urinary excretion of cyclic AMP and aldosterone in hypoparathyroid patients.", "content": "The effect of sodium depletion on plasma renin activity (PRA), urinary cyclic AMP and urinary aldosterone excretion was studied in hypoparathyroid patients whose basal urinary cylic AMP excretion (urinary cAMP) was less than 50% of that observed in normal subjects. During 7 days of sodium depletion, PRA, urinary aldosterone and urinary cAMP each rose significantly. Administration of the beta-blocker propranolol, 160 mg/day, during 5 further days of sodium depletion produced a fall in PRA and urinary cAMP, but no change in urinary aldosterone excretion. The dissociation in these effects suggests that the increase in aldosterone secretion during sodium depletion may be mediated by pathways other than the renin-angiotensin and adenyl cyclase systems. There was a high degree of correlation between PRA and urinary cAMP (P less than 0.001) during the period of sodium depletion, but not significant relationship between these parameters was found during control and propranolol phases, or in control studies in normal subjects. These findings suggest that beta-adrenergic receptors have a role in mediating the effects of sodium depletion upon renin secretion and adenyl cyclase activity.", "contents": "Effects of sodium depletion on plasma renin activity and on the urinary excretion of cyclic AMP and aldosterone in hypoparathyroid patients. The effect of sodium depletion on plasma renin activity (PRA), urinary cyclic AMP and urinary aldosterone excretion was studied in hypoparathyroid patients whose basal urinary cylic AMP excretion (urinary cAMP) was less than 50% of that observed in normal subjects. During 7 days of sodium depletion, PRA, urinary aldosterone and urinary cAMP each rose significantly. Administration of the beta-blocker propranolol, 160 mg/day, during 5 further days of sodium depletion produced a fall in PRA and urinary cAMP, but no change in urinary aldosterone excretion. The dissociation in these effects suggests that the increase in aldosterone secretion during sodium depletion may be mediated by pathways other than the renin-angiotensin and adenyl cyclase systems. There was a high degree of correlation between PRA and urinary cAMP (P less than 0.001) during the period of sodium depletion, but not significant relationship between these parameters was found during control and propranolol phases, or in control studies in normal subjects. These findings suggest that beta-adrenergic receptors have a role in mediating the effects of sodium depletion upon renin secretion and adenyl cyclase activity."} {"id": "PMID:166091", "title": "Adrenal function in hirsutism I. Diurnal change and response of plasma androstenedione, testosterone, 17-hydroxyprogesterone, cortisol, LH and FSH to dexamethasone and 1/2 unit of ACTH.", "content": "ACTH dependency of plasma androstenedione (A) and testosterone (T) was determined in normal and hirsute women by measuring the magnitude of change of A and T between the time of the cortisol (F) peak and F nadir in a diurnal study. There was a significant diurnal rhythm of A synchronous with F in both normal and hirsute women (P less than 0.01). Five of 12 hirsute women had a greater than normal diurnal swing of A (P less than 0.05), but only 2 of the 12 had a greater than normal diurnal swing of T. Responsiveness of A and T to 1/2 unit of intravenous ACTH was determined after dexamethasone 1 mg was given the night before. Plasma A and T were elevated in most of the hirsute women during acute ACTH suppression by dexamethasone, indicating ACTH-independent hypersecretion of androgens. Nine of 17 hirsute women had a greater than normal A response to ACTH (P less than 0.05). Those who had an exaggerated diurnal swing of A also had hyper-responsiveness of A secretion to ACTH. Only 2 hirsute women had an exaggerated T response to ACTH. Some T levels were decreased by ACTH. Seven of the 9 hiruste women who had an exaggerated A response to ACTH had a normal maximum F response, but a greater than normal 17-hydroxy-progesterone (17-OHP) response to ACTH with a high 17-OHP to F ratio, suggesting they have a mild but compensated reduction in 21-hydroxylase or 11beta-hydroxylase activity. Two women with hyper-responsiveness of A secretion had low F and 17-OHP responses to ACTH suggesting reduced C21 but intact C19 3beta-hydroxysteroid dehydrogenase-delta-5,-4 isomerase activity. These apparent reduced enzyme activity may not be congenital, but induced by an altered hormonal milieu such as an abnormal androgen-estrogen ratio. It is concluded that ACTH uniformly stimulated A secretion but not T secretion and that approximately 50% of the hirsute women had ACTH-dependent hypersecretion of A, but most of these also had concurrent ACTH-independent hypersecretion of androgens.", "contents": "Adrenal function in hirsutism I. Diurnal change and response of plasma androstenedione, testosterone, 17-hydroxyprogesterone, cortisol, LH and FSH to dexamethasone and 1/2 unit of ACTH. ACTH dependency of plasma androstenedione (A) and testosterone (T) was determined in normal and hirsute women by measuring the magnitude of change of A and T between the time of the cortisol (F) peak and F nadir in a diurnal study. There was a significant diurnal rhythm of A synchronous with F in both normal and hirsute women (P less than 0.01). Five of 12 hirsute women had a greater than normal diurnal swing of A (P less than 0.05), but only 2 of the 12 had a greater than normal diurnal swing of T. Responsiveness of A and T to 1/2 unit of intravenous ACTH was determined after dexamethasone 1 mg was given the night before. Plasma A and T were elevated in most of the hirsute women during acute ACTH suppression by dexamethasone, indicating ACTH-independent hypersecretion of androgens. Nine of 17 hirsute women had a greater than normal A response to ACTH (P less than 0.05). Those who had an exaggerated diurnal swing of A also had hyper-responsiveness of A secretion to ACTH. Only 2 hirsute women had an exaggerated T response to ACTH. Some T levels were decreased by ACTH. Seven of the 9 hiruste women who had an exaggerated A response to ACTH had a normal maximum F response, but a greater than normal 17-hydroxy-progesterone (17-OHP) response to ACTH with a high 17-OHP to F ratio, suggesting they have a mild but compensated reduction in 21-hydroxylase or 11beta-hydroxylase activity. Two women with hyper-responsiveness of A secretion had low F and 17-OHP responses to ACTH suggesting reduced C21 but intact C19 3beta-hydroxysteroid dehydrogenase-delta-5,-4 isomerase activity. These apparent reduced enzyme activity may not be congenital, but induced by an altered hormonal milieu such as an abnormal androgen-estrogen ratio. It is concluded that ACTH uniformly stimulated A secretion but not T secretion and that approximately 50% of the hirsute women had ACTH-dependent hypersecretion of A, but most of these also had concurrent ACTH-independent hypersecretion of androgens."} {"id": "PMID:166092", "title": "Metabolism of cholesteryl esters of rat very low density lipoproteins.", "content": "Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent.", "contents": "Metabolism of cholesteryl esters of rat very low density lipoproteins. Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent."} {"id": "PMID:166093", "title": "Metabolism of bovine parathyroid hormone. Immunological and biological characteristics of fragments generated by liver perfusion.", "content": "The metabolism of bovine parathyroid hormone (PTH) by the perfused rat liver was studied. Labeled hormone, with or without cold hormone, was infused into the circulating perfusion medium containing various calcium concentrations. Pefusate samples at various time periods after the introduction of PTH into the system were chromatographed on Bio-gel P-10; radioactivity and/or immunoreactivity were measured in eluted fractions. Before the perfusion, all immuno- and radioactivity eluted in a single peak, with an apparent mol wt of 9,500 (peak I). After perfusion for 15 min, two other peaks with approximate mol wt of 7,000 (peak II) and 3,500 (peak III) were discernible. Peak I contained both NH2-terminal and COOH-terminal immunoreactivity and was biologically active at all time periods tested. The relative contribution of NH2-terminal and COOH-terminal immunoreactivity to the total immunoreactivity remained constant in this peak throughout the perfusion. In every respect, peak I had the characteristics of intact hormone. At all times, peak II consisted of only COOH-terminal immunoreactivity and was biologically inactive. At early time periods, peak III contained predominantly NH2-terminal immunoreactivity and was biologically active. With time, the relative contribution of NH2-terminal immunoreactivity decreased strikingly while that of COOH-terminal immunoreactivity increased. The three peaks identified in these experiments were analogous in size, biological activity, and immunological characteristics to those we have previously described for fractionated human hyperparathyroid serum. The rate of metabolism of PTH appeared to be regulated by the calcium concentration in the medium. At a high concentration of calcium (greater than 11 mg/100 ml), PTH metabolism was greatly retarded. At a low concentration of calcium (smaller than 5 mg/100 ml), the rate of metabolism was greatly increased. The physiological significance of our observations on the metabolism of PTH by isolated perfused rat liver is not known. However, since such metabolism results in a biologically active fragment, it is suggested that metabolism of intact hormone may be required before full biological expression is possible.", "contents": "Metabolism of bovine parathyroid hormone. Immunological and biological characteristics of fragments generated by liver perfusion. The metabolism of bovine parathyroid hormone (PTH) by the perfused rat liver was studied. Labeled hormone, with or without cold hormone, was infused into the circulating perfusion medium containing various calcium concentrations. Pefusate samples at various time periods after the introduction of PTH into the system were chromatographed on Bio-gel P-10; radioactivity and/or immunoreactivity were measured in eluted fractions. Before the perfusion, all immuno- and radioactivity eluted in a single peak, with an apparent mol wt of 9,500 (peak I). After perfusion for 15 min, two other peaks with approximate mol wt of 7,000 (peak II) and 3,500 (peak III) were discernible. Peak I contained both NH2-terminal and COOH-terminal immunoreactivity and was biologically active at all time periods tested. The relative contribution of NH2-terminal and COOH-terminal immunoreactivity to the total immunoreactivity remained constant in this peak throughout the perfusion. In every respect, peak I had the characteristics of intact hormone. At all times, peak II consisted of only COOH-terminal immunoreactivity and was biologically inactive. At early time periods, peak III contained predominantly NH2-terminal immunoreactivity and was biologically active. With time, the relative contribution of NH2-terminal immunoreactivity decreased strikingly while that of COOH-terminal immunoreactivity increased. The three peaks identified in these experiments were analogous in size, biological activity, and immunological characteristics to those we have previously described for fractionated human hyperparathyroid serum. The rate of metabolism of PTH appeared to be regulated by the calcium concentration in the medium. At a high concentration of calcium (greater than 11 mg/100 ml), PTH metabolism was greatly retarded. At a low concentration of calcium (smaller than 5 mg/100 ml), the rate of metabolism was greatly increased. The physiological significance of our observations on the metabolism of PTH by isolated perfused rat liver is not known. However, since such metabolism results in a biologically active fragment, it is suggested that metabolism of intact hormone may be required before full biological expression is possible."} {"id": "PMID:166094", "title": "The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes.", "content": "The capacity of human phagocytes to generate superoxide anion (O2-), a free radical of oxygen, and a possible role for this radical or its derivatives in the killing of phagocytized bacteria were explored using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Superoxide dismutase, which removes O2-, consistently inhibited phagocytosis-associated nitroblue tetrazolium (NBT) reduction indicating the involvement of O2- in this process. Similarly, superoxide dismutase inhibited the luminescence that occurs with phagocytosis, implicating O2- in this phenomenon, perhaps through its spontaneous dismutation into singlet oxygen. Subcellular fractions from homogenates of both normal and CGD leukocytes generated O2- effectively in the presence of NADH as substrate. However, O2- generation by intact cells during phagocytosis was markedly diminished in nine patients with CGD. Leukocytes from mothers determined to be carriers of X-linked recessive CGD by intermediate phagocytic reduction of NBT elaborated O2- to an intermediate extent, further demonstrating the interrelationship between NBT reduction and O2- generation in phagocytizing cells. Activity of superoxide dismutase, the enzyme responsible for protecting the cell from the damaging effects of O2-, was approximately equal in homogenates of normal and CGD granulocytes. Polyacrylamide electrophoresis separated this activity into a minor band that appeared to be the manganese-containing superoxide dismutase associated with mitochondria and a more concentrated, cyanide-sensitive, cytosol form of the enzyme with electrophoretic mobility that corresponded to that of erythrocyte cuprozinc superoxide dismutase. Superoxide dismutase inhibited the phagocytic killing of Escherichia coli, Staphylococcus aureus, and Streptococcus viridans. A similar inhibitory effect was noted with catalase which removes hydrogen peroxide. Neither enzyme inhibited the ingestion of bacteria. Peroxide and O2- are believed to interact to generate the potent oxidant, hydroxyl radical (.OH). A requirement for .OH in the phagocytic bactericidal event might explain the apparent requirement for both O2- and H2O2 for such activity. In agreement with this possibility, benzoate and mannitol, scavengers of .OH, inhibited phagocytic bactericidal activity. Generation of singlet oxygen from O2- and .OH also might explain these findings. It would seem clear from these and other studies that the granulo cyte elaborates O2- as a concomitant of the respiratory burst that occurs with phagocytosis. To what extent the energy inherent in O2- is translated into microbialdeath through O2- itself, hydrogen peroxide, .OH, singlet oxygen, or some other agent remains to be clearly defined.", "contents": "The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes. The capacity of human phagocytes to generate superoxide anion (O2-), a free radical of oxygen, and a possible role for this radical or its derivatives in the killing of phagocytized bacteria were explored using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Superoxide dismutase, which removes O2-, consistently inhibited phagocytosis-associated nitroblue tetrazolium (NBT) reduction indicating the involvement of O2- in this process. Similarly, superoxide dismutase inhibited the luminescence that occurs with phagocytosis, implicating O2- in this phenomenon, perhaps through its spontaneous dismutation into singlet oxygen. Subcellular fractions from homogenates of both normal and CGD leukocytes generated O2- effectively in the presence of NADH as substrate. However, O2- generation by intact cells during phagocytosis was markedly diminished in nine patients with CGD. Leukocytes from mothers determined to be carriers of X-linked recessive CGD by intermediate phagocytic reduction of NBT elaborated O2- to an intermediate extent, further demonstrating the interrelationship between NBT reduction and O2- generation in phagocytizing cells. Activity of superoxide dismutase, the enzyme responsible for protecting the cell from the damaging effects of O2-, was approximately equal in homogenates of normal and CGD granulocytes. Polyacrylamide electrophoresis separated this activity into a minor band that appeared to be the manganese-containing superoxide dismutase associated with mitochondria and a more concentrated, cyanide-sensitive, cytosol form of the enzyme with electrophoretic mobility that corresponded to that of erythrocyte cuprozinc superoxide dismutase. Superoxide dismutase inhibited the phagocytic killing of Escherichia coli, Staphylococcus aureus, and Streptococcus viridans. A similar inhibitory effect was noted with catalase which removes hydrogen peroxide. Neither enzyme inhibited the ingestion of bacteria. Peroxide and O2- are believed to interact to generate the potent oxidant, hydroxyl radical (.OH). A requirement for .OH in the phagocytic bactericidal event might explain the apparent requirement for both O2- and H2O2 for such activity. In agreement with this possibility, benzoate and mannitol, scavengers of .OH, inhibited phagocytic bactericidal activity. Generation of singlet oxygen from O2- and .OH also might explain these findings. It would seem clear from these and other studies that the granulo cyte elaborates O2- as a concomitant of the respiratory burst that occurs with phagocytosis. To what extent the energy inherent in O2- is translated into microbialdeath through O2- itself, hydrogen peroxide, .OH, singlet oxygen, or some other agent remains to be clearly defined."} {"id": "PMID:166095", "title": "Inorganic pyrophosphate pool size and turnover rate in arthritic joints.", "content": "Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.", "contents": "Inorganic pyrophosphate pool size and turnover rate in arthritic joints. Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition."} {"id": "PMID:166101", "title": "Plaque accumulation on composite surfaces after various finising procedures.", "content": "A clinical study was undertaken to determine the rate at which plaque accumulates on the surfaces of composite restorations on which four finishing techniques were used. Plaque on these surfaces was compared with that on control surfaces with polished metallic or glazed porcelain restorations, and unrestored enamel surfaces. Composite surfaces were covered with plaque after 24 hours regardless of the finishing technique used. Plaque did not collect on adjacent control teeth to this degree until the third day, although the diffence remained statistically significant. Surface discrepancies on the polished composites were shown in scanning electron micrographs and with laboratory measurements.", "contents": "Plaque accumulation on composite surfaces after various finising procedures. A clinical study was undertaken to determine the rate at which plaque accumulates on the surfaces of composite restorations on which four finishing techniques were used. Plaque on these surfaces was compared with that on control surfaces with polished metallic or glazed porcelain restorations, and unrestored enamel surfaces. Composite surfaces were covered with plaque after 24 hours regardless of the finishing technique used. Plaque did not collect on adjacent control teeth to this degree until the third day, although the diffence remained statistically significant. Surface discrepancies on the polished composites were shown in scanning electron micrographs and with laboratory measurements."} {"id": "PMID:166102", "title": "Effect of Bordetella pertussis extract and vasoactive amines on vascular permeability.", "content": "Vasxular permeability to Evans blue dye and 131-I-labeled human serum albumin was studied in normal mice and in mice treated with alkaline saline extracts (SE) from Bordetella pertussis cells. Skin sites inoculated intracutaneously with small doses of histamine, serotonin, or a combination of these 2 substances were more permeable in SE-treated mice than in normal animals. Intravenously administered catecholamines were able to reduce in varying degrees the vascular permeability induced by serotonin or by histamine in normal mice; in SE-treated mice the catecholamines were less effective. The relative effectiveness of intravenously administered catecholamines to reduce vascular permeability in normal or SE-treated mice was ranked as follows: isoproterenol greater than epinephrine greater than norepinephrine. When catecholamines were given concomitantly with histamine and serotonin in the skin test site, the permeability in both normal and SE-treated mice was again reduced or blocked, but isoproterenol was only weakly effective in this instance. Their relative effectiveness was epinephrine greater than norepinephrine greater than isoproterenol. The possible explanations for these results are discussed.", "contents": "Effect of Bordetella pertussis extract and vasoactive amines on vascular permeability. Vasxular permeability to Evans blue dye and 131-I-labeled human serum albumin was studied in normal mice and in mice treated with alkaline saline extracts (SE) from Bordetella pertussis cells. Skin sites inoculated intracutaneously with small doses of histamine, serotonin, or a combination of these 2 substances were more permeable in SE-treated mice than in normal animals. Intravenously administered catecholamines were able to reduce in varying degrees the vascular permeability induced by serotonin or by histamine in normal mice; in SE-treated mice the catecholamines were less effective. The relative effectiveness of intravenously administered catecholamines to reduce vascular permeability in normal or SE-treated mice was ranked as follows: isoproterenol greater than epinephrine greater than norepinephrine. When catecholamines were given concomitantly with histamine and serotonin in the skin test site, the permeability in both normal and SE-treated mice was again reduced or blocked, but isoproterenol was only weakly effective in this instance. Their relative effectiveness was epinephrine greater than norepinephrine greater than isoproterenol. The possible explanations for these results are discussed."} {"id": "PMID:166116", "title": "Evidence for the complex nature of the ganglioside receptor for cholera toxin.", "content": "Choleragenoid binds more slowly and less strongly than cholera toxin to intestinal mucosal cells, and even less strongly to free ganglioside in solution. However, binding to ganglioside is greatly enhanced when the ganglioside is in the form of an insoluble complex with cerebroside. These findings suggest that both the binding and the active components of the toxin molecule may be necessary for optimal binding of the toxin to the intact cell, and that the ganglioside in the cell receptor is in a complex form. Choleragenoid only partially blocks the action of the toxin on ruptured cells. This observation indicates that, while binding to a membrane receptor is necessary for the action of the toxin on the whole cell, it is possible to activate adenyl cyclase in a perforated cell by a process apparently independent of membrane binding; however, this activation may be possible only if the toxin preparation contains the active component dissociated from choleragenoid.", "contents": "Evidence for the complex nature of the ganglioside receptor for cholera toxin. Choleragenoid binds more slowly and less strongly than cholera toxin to intestinal mucosal cells, and even less strongly to free ganglioside in solution. However, binding to ganglioside is greatly enhanced when the ganglioside is in the form of an insoluble complex with cerebroside. These findings suggest that both the binding and the active components of the toxin molecule may be necessary for optimal binding of the toxin to the intact cell, and that the ganglioside in the cell receptor is in a complex form. Choleragenoid only partially blocks the action of the toxin on ruptured cells. This observation indicates that, while binding to a membrane receptor is necessary for the action of the toxin on the whole cell, it is possible to activate adenyl cyclase in a perforated cell by a process apparently independent of membrane binding; however, this activation may be possible only if the toxin preparation contains the active component dissociated from choleragenoid."} {"id": "PMID:166117", "title": "Antiviral activity of an adenosine deaminase inhibitor: decreased replication of herpes simplex virus.", "content": "A unique seven-membered heterocyclic-ring inhibitor of adenosine deaminase was studied. One preparation of the compound inhibited replication of herpes simplex virus in the absence of adenine arabinoside. In this capacity, the minimal inhibitory concentration of deaminase inhibitor for herpes simplex virus type 1 (HSV-1), with 50 percent reduction of plaque-forming units as the end point, was 37.7 mug/ml. This activity compared favorably with the inhibitory activity of ara-hypoxanthine (34.1 mug/ml). Another preparation of deaminase inhibitor lacked antiviral activity. On the other hand, the adenosine deaminase inhibitor was active at a concentration of 0.009 mug/ml as a potentiator of the inhibition of HSV-1 by adenine arabinoside. The potentiation of adenine arabinoside by deaminase inhibitor is about 4,000 times more potent than the activity of the direct inhibitory effect on HSV-1. The nature of the possible contaminant of the preparation in question is unknown. Coformycin, another inhibitor of adenosine deaminase, had no antiviral activity in the absence of adenine arabinoside.", "contents": "Antiviral activity of an adenosine deaminase inhibitor: decreased replication of herpes simplex virus. A unique seven-membered heterocyclic-ring inhibitor of adenosine deaminase was studied. One preparation of the compound inhibited replication of herpes simplex virus in the absence of adenine arabinoside. In this capacity, the minimal inhibitory concentration of deaminase inhibitor for herpes simplex virus type 1 (HSV-1), with 50 percent reduction of plaque-forming units as the end point, was 37.7 mug/ml. This activity compared favorably with the inhibitory activity of ara-hypoxanthine (34.1 mug/ml). Another preparation of deaminase inhibitor lacked antiviral activity. On the other hand, the adenosine deaminase inhibitor was active at a concentration of 0.009 mug/ml as a potentiator of the inhibition of HSV-1 by adenine arabinoside. The potentiation of adenine arabinoside by deaminase inhibitor is about 4,000 times more potent than the activity of the direct inhibitory effect on HSV-1. The nature of the possible contaminant of the preparation in question is unknown. Coformycin, another inhibitor of adenosine deaminase, had no antiviral activity in the absence of adenine arabinoside."} {"id": "PMID:166119", "title": "The effect of dexamethasone on the control of plasma aldosterone concentration in normal recumbent man.", "content": "In order to evaluate the control of the circadian rhythm of plasma aldosterone concentration in man, plasma aldosterone, cortisol, sodium and potassium concentrations, and plasma renin activity (PRA) were measured in samples obtained at 20-minute intervals from 0200 to 0800 in sodium repleted (180 mEq. per day of diet) and sodium depleted (22 mEq. per day of diet) normal subjects. During sodium replete studies, plasma aldosterone and cortisol concentrations were significantly correlated (p greater than 0.01) in all 4 subjects. Plasma aldosterone also correlated with PRA (p greather than 0.01) in 2 subjects and with potassium (p greater than 0.01) in one. Episodic increases in plasma aldosterone concentration were observed despite suppression of ACTH by dexamethasone treatment. Plasma aldosterone concentrations were significantly correlated with PRA (p greater than 0.05 and p greater than 0.01) in only 2 of 4 subjects under these conditions. Following sodium restriction, plasma aldosterone concentrations were not significantly correlated with plasma cortisol and only infrequently with either PRA or potassium. When dexamethasone was administered during the low sodium diet, correlations with PRA (p greater than 0.001) were seen in 2 of 3 subjects and with potassium (p greater than 0.01) in 1 of 3 subjects. There was no significant correlation between plasma aldosterone and sodium concentration during any of the studies. These results are compatible with the concept that the relative importance of PRA, ACTH, and potassium in inducing changes in aldosterone production during the early morning hours is partially dependent upon dietary sodium, but also varies between individuals studied during similar sodium diets. The episodic alterations of plasma aldosterone concentration continued after ACTH was suppressed by dexamethasone pretreatment. These changes, in the absence of a consistent significant correlation with PRA and sodium and potassium concentrations, further suggest that another factor(s) may be important in controlling aldosterone production in recumbent normal subjects.", "contents": "The effect of dexamethasone on the control of plasma aldosterone concentration in normal recumbent man. In order to evaluate the control of the circadian rhythm of plasma aldosterone concentration in man, plasma aldosterone, cortisol, sodium and potassium concentrations, and plasma renin activity (PRA) were measured in samples obtained at 20-minute intervals from 0200 to 0800 in sodium repleted (180 mEq. per day of diet) and sodium depleted (22 mEq. per day of diet) normal subjects. During sodium replete studies, plasma aldosterone and cortisol concentrations were significantly correlated (p greater than 0.01) in all 4 subjects. Plasma aldosterone also correlated with PRA (p greather than 0.01) in 2 subjects and with potassium (p greater than 0.01) in one. Episodic increases in plasma aldosterone concentration were observed despite suppression of ACTH by dexamethasone treatment. Plasma aldosterone concentrations were significantly correlated with PRA (p greater than 0.05 and p greater than 0.01) in only 2 of 4 subjects under these conditions. Following sodium restriction, plasma aldosterone concentrations were not significantly correlated with plasma cortisol and only infrequently with either PRA or potassium. When dexamethasone was administered during the low sodium diet, correlations with PRA (p greater than 0.001) were seen in 2 of 3 subjects and with potassium (p greater than 0.01) in 1 of 3 subjects. There was no significant correlation between plasma aldosterone and sodium concentration during any of the studies. These results are compatible with the concept that the relative importance of PRA, ACTH, and potassium in inducing changes in aldosterone production during the early morning hours is partially dependent upon dietary sodium, but also varies between individuals studied during similar sodium diets. The episodic alterations of plasma aldosterone concentration continued after ACTH was suppressed by dexamethasone pretreatment. These changes, in the absence of a consistent significant correlation with PRA and sodium and potassium concentrations, further suggest that another factor(s) may be important in controlling aldosterone production in recumbent normal subjects."} {"id": "PMID:166120", "title": "Conservative surgical treatment of mixed tumours of the parotid gland.", "content": "The author presents 44 cases of mixed tumours of the parotid gland, operated on by simple enucleation and not radical removal of the gland, which most authors maintain must always be carried out. There were 6 recurrences (13.6 percent), and the last appeared in 1965. He maintains that simple enucleation is justified. It is reasonable to hope for a further decrease in the number of recurrences with future improvement in surgical techniques.", "contents": "Conservative surgical treatment of mixed tumours of the parotid gland. The author presents 44 cases of mixed tumours of the parotid gland, operated on by simple enucleation and not radical removal of the gland, which most authors maintain must always be carried out. There were 6 recurrences (13.6 percent), and the last appeared in 1965. He maintains that simple enucleation is justified. It is reasonable to hope for a further decrease in the number of recurrences with future improvement in surgical techniques."} {"id": "PMID:166130", "title": "Gel filtration of human urinary immunoreactive luteinizing hormone.", "content": "In human urinary concentrates and also in a urinary gonadotrophin standard (2nd IRP-HMG), gel-filtration analysis revealed three main peaks of immunoassayable luteinizing hormone (LH). A similar analysis of LH extracted from human pituitaries showed most of the activity in a peak of larger molecular weight, and only minor fractions in the positions of the urinary peaks. In an extract of normal human serum, analyss showed only one similar peak of large molecular weight, which also emerged before the urinary peaks. During an i.v. infusion of pituitary LH into normal men, the urinary LH activity increased but was still found only in the same three peaks on gel filtration, and all were of a molecular weight smaller than that of the infused material; but a higher proportion of the urinary LH was found in the earliest of these peaks compared with that found before infusion. Conversely, 20-35 h after the i.v. infusion, there was a slightly higher proportion of LH activity in the third peak of smallest molecular weight. These findings suggest that the urinary immunoassayable LH, which is found in three peaks of different molecular weights, is derived from the pituitary or serum LH of higher molecular weight. The changes in the proportions of larger or smaller molecular weight fractions in the urine during and after LH infusion suggest that the earliest peak may be disaggregated serum LH, while the last or smallest molecular weight peak may comprise metabolites of LH.", "contents": "Gel filtration of human urinary immunoreactive luteinizing hormone. In human urinary concentrates and also in a urinary gonadotrophin standard (2nd IRP-HMG), gel-filtration analysis revealed three main peaks of immunoassayable luteinizing hormone (LH). A similar analysis of LH extracted from human pituitaries showed most of the activity in a peak of larger molecular weight, and only minor fractions in the positions of the urinary peaks. In an extract of normal human serum, analyss showed only one similar peak of large molecular weight, which also emerged before the urinary peaks. During an i.v. infusion of pituitary LH into normal men, the urinary LH activity increased but was still found only in the same three peaks on gel filtration, and all were of a molecular weight smaller than that of the infused material; but a higher proportion of the urinary LH was found in the earliest of these peaks compared with that found before infusion. Conversely, 20-35 h after the i.v. infusion, there was a slightly higher proportion of LH activity in the third peak of smallest molecular weight. These findings suggest that the urinary immunoassayable LH, which is found in three peaks of different molecular weights, is derived from the pituitary or serum LH of higher molecular weight. The changes in the proportions of larger or smaller molecular weight fractions in the urine during and after LH infusion suggest that the earliest peak may be disaggregated serum LH, while the last or smallest molecular weight peak may comprise metabolites of LH."} {"id": "PMID:166131", "title": "Physiological variation in abundance of oestrogen specific high-affinity binding sites in hypothalamus, pituitary and uterus of the rat.", "content": "High-affinity binding of [2,4,6,7-3-H]oestradiol-17 beta has been studied in cytosols prepared from hypothalami, pituitaries and uteri of female rats killed at different stages of the oestrous cycle, and in cytosols prepared from the hypothalami and pituitaries of male rats. In all cases the equilibrium dissociation constant of reaction was of the order of 10- minus 10 mol/1. The number of available high affinity sites per tissue (n) varied with physiological state. In females, n fluctuated with the oestrus cycle. In hypothalamus and pituitary, n fell by about 60 and 40% respectively in pro-oestrus, replenishment occurred during oestrus but could be delayed by phenobarbitone administration during the afternoon of pro-oestrus. In the uterus, n varied biphasically, there being peaks during dioestrus and oestrus, and troughs at pro-oestrus and metoestrus. The numbers of available sites at metoestrus were 12-5 times 10-9, 10-6 times 10-10 and 24-4 times times 10-10 for hypothalamus, pituitary and uterus respectively. In male rats, values for n were similar to those obtained for females at pro-oestrus (n/hypothalamus equals 6-8 times 10-9, n/pituitary equals 4-2 times 10-10). Binding was oestrogen specific in all the tissues studied.", "contents": "Physiological variation in abundance of oestrogen specific high-affinity binding sites in hypothalamus, pituitary and uterus of the rat. High-affinity binding of [2,4,6,7-3-H]oestradiol-17 beta has been studied in cytosols prepared from hypothalami, pituitaries and uteri of female rats killed at different stages of the oestrous cycle, and in cytosols prepared from the hypothalami and pituitaries of male rats. In all cases the equilibrium dissociation constant of reaction was of the order of 10- minus 10 mol/1. The number of available high affinity sites per tissue (n) varied with physiological state. In females, n fluctuated with the oestrus cycle. In hypothalamus and pituitary, n fell by about 60 and 40% respectively in pro-oestrus, replenishment occurred during oestrus but could be delayed by phenobarbitone administration during the afternoon of pro-oestrus. In the uterus, n varied biphasically, there being peaks during dioestrus and oestrus, and troughs at pro-oestrus and metoestrus. The numbers of available sites at metoestrus were 12-5 times 10-9, 10-6 times 10-10 and 24-4 times times 10-10 for hypothalamus, pituitary and uterus respectively. In male rats, values for n were similar to those obtained for females at pro-oestrus (n/hypothalamus equals 6-8 times 10-9, n/pituitary equals 4-2 times 10-10). Binding was oestrogen specific in all the tissues studied."} {"id": "PMID:166133", "title": "A comparison of the effects of the calcitonins, steroid hormones and thyroid hormones on the response of bone to parathyroid hormone in tissue culture.", "content": "A bone culture system was used to compare the effects of several hormones on the response of 5-day-old mouse calvaria to parathyroid hormone (PTH). The results showed that salmon calcitonin was almost 10-5 times more active than any other hormone in preventing the PTH-induced release of calcium and caused a dose-related inhibition of calcium release over a range of 0-2-200 milli MRC units/culture. A high dose of calcitonin (200 milli MRC units) caused a net accretion of calcium in the absence of PTH. Progesterone and testosterone were more active than the naturally occurring oestrogens although a synthetic oestrogen (stillboestrol diphosphate) had approximately the same potency. High concentrations of these hormones caused a net accretion of calcium whether or not PTH was present. Cortisol was only effective at high doses, as was the steroid precursor cholesterol. In the present culture system the thyroid hormones (triiodothyronine and thyroxine) inhibited the action of PTH. It was concluded that these agents acted in a similar fashion to the oestrogens. That is, they prevented the accumulation of citric acid induced by PTH by reducing the rate of glycolysis. None of the hormones affected the inhibition of citrate oxidation caused by PTH. The results also showed that, whilst these hormones inhibited PTH-mediated bone resorption, they had an action on bone independent of PTH. Experiments with clomiphene citrate failed to demonstrate an oestrogen receptor in bone.", "contents": "A comparison of the effects of the calcitonins, steroid hormones and thyroid hormones on the response of bone to parathyroid hormone in tissue culture. A bone culture system was used to compare the effects of several hormones on the response of 5-day-old mouse calvaria to parathyroid hormone (PTH). The results showed that salmon calcitonin was almost 10-5 times more active than any other hormone in preventing the PTH-induced release of calcium and caused a dose-related inhibition of calcium release over a range of 0-2-200 milli MRC units/culture. A high dose of calcitonin (200 milli MRC units) caused a net accretion of calcium in the absence of PTH. Progesterone and testosterone were more active than the naturally occurring oestrogens although a synthetic oestrogen (stillboestrol diphosphate) had approximately the same potency. High concentrations of these hormones caused a net accretion of calcium whether or not PTH was present. Cortisol was only effective at high doses, as was the steroid precursor cholesterol. In the present culture system the thyroid hormones (triiodothyronine and thyroxine) inhibited the action of PTH. It was concluded that these agents acted in a similar fashion to the oestrogens. That is, they prevented the accumulation of citric acid induced by PTH by reducing the rate of glycolysis. None of the hormones affected the inhibition of citrate oxidation caused by PTH. The results also showed that, whilst these hormones inhibited PTH-mediated bone resorption, they had an action on bone independent of PTH. Experiments with clomiphene citrate failed to demonstrate an oestrogen receptor in bone."} {"id": "PMID:166142", "title": "Development of parthenogenetic membranes in double-yolked and injected chicken eggs.", "content": "Development of parthenogenetic eggs is expressed in a Dark Cornish stock by either membrane or embryo formation. Double-yolked eggs have membranes developing in zero, one, or two yolks. The incidence of double-yolked eggs with two membranes was higher than expected when compared with the incidence of single-yolked eggs from the same hens. Membrane formation was increased over that of the controls by injecting saline, Ringer's solution, or ground crude membranes. Yolk and membranes filtered through a 3 mu filter or autoclaved did not increase membrane formation over that of the controls. Fertile membranes behaved like parthenogenetic membranes.", "contents": "Development of parthenogenetic membranes in double-yolked and injected chicken eggs. Development of parthenogenetic eggs is expressed in a Dark Cornish stock by either membrane or embryo formation. Double-yolked eggs have membranes developing in zero, one, or two yolks. The incidence of double-yolked eggs with two membranes was higher than expected when compared with the incidence of single-yolked eggs from the same hens. Membrane formation was increased over that of the controls by injecting saline, Ringer's solution, or ground crude membranes. Yolk and membranes filtered through a 3 mu filter or autoclaved did not increase membrane formation over that of the controls. Fertile membranes behaved like parthenogenetic membranes."} {"id": "PMID:166143", "title": "The physiological function of nitrate reduction in Clostridium perfringens.", "content": "Fermentation-balance studies have been carried out on Clostridium perfringens grown in the presence and absence of nitrate in the medium. Nitrate is able to serve as an electron acceptor for these bacteria, permitting increased growth yields over those obtained in its absence. This increase is due to an increase in the proportion of metabolite molecules which can participate in substrate-level phosphorylation reactions when an inorganic acceptor is available. The nitrate reduction can be regarded as a primitive form of anaerobic respiration in these bacteria, since it is clearly coupled to their energy metabolism and is not assimilative in function. We believe that the existence of this kind of energy metabolism in these bacteria has significant evolutionary implications.", "contents": "The physiological function of nitrate reduction in Clostridium perfringens. Fermentation-balance studies have been carried out on Clostridium perfringens grown in the presence and absence of nitrate in the medium. Nitrate is able to serve as an electron acceptor for these bacteria, permitting increased growth yields over those obtained in its absence. This increase is due to an increase in the proportion of metabolite molecules which can participate in substrate-level phosphorylation reactions when an inorganic acceptor is available. The nitrate reduction can be regarded as a primitive form of anaerobic respiration in these bacteria, since it is clearly coupled to their energy metabolism and is not assimilative in function. We believe that the existence of this kind of energy metabolism in these bacteria has significant evolutionary implications."} {"id": "PMID:166146", "title": "The induction of intractranial neoplasms by the inoculation of avian sarcoma virus in perinatal and adult rats.", "content": "The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology of tumors induced by a uniform inoculum of the Bratislava-77 strain of ASV in adult, neonatal, and fetal Fischer 344 rats. Post-inoculation mortality varied significantly between groups inoculated at 1, 10 and 100 days and was most precipitous in perinatally inoculated rats. Percentage of tumor induction declined from 100% among rats inoculated at 1 day of age to 50% among rats inoculated at 100 days of age. The mean number of tumors/animal was inversely proportional to the logarithm of the age at inoculation. A large majority of tumors in each group were glial; the remainder were mesenchymal and mixed glial and mesenchymal. Neuroglial tumors included: mixed gliomas with oligodendroglial and astrocytic elements; and gemistocytic, pilocytic, fibrillary, anaplastic and protoplasmic astrocytomas. Tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in older animals tended to be purely astrocytic and of uniform cell type. Mesenchymal tumors occurred primarily in the meninges and were common among animals inoculated perinatally but were rare among animals inoculated as adults. No neuronal tumors were encountered even among rats inoculated as early as 16 days of gestation.", "contents": "The induction of intractranial neoplasms by the inoculation of avian sarcoma virus in perinatal and adult rats. The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology of tumors induced by a uniform inoculum of the Bratislava-77 strain of ASV in adult, neonatal, and fetal Fischer 344 rats. Post-inoculation mortality varied significantly between groups inoculated at 1, 10 and 100 days and was most precipitous in perinatally inoculated rats. Percentage of tumor induction declined from 100% among rats inoculated at 1 day of age to 50% among rats inoculated at 100 days of age. The mean number of tumors/animal was inversely proportional to the logarithm of the age at inoculation. A large majority of tumors in each group were glial; the remainder were mesenchymal and mixed glial and mesenchymal. Neuroglial tumors included: mixed gliomas with oligodendroglial and astrocytic elements; and gemistocytic, pilocytic, fibrillary, anaplastic and protoplasmic astrocytomas. Tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in older animals tended to be purely astrocytic and of uniform cell type. Mesenchymal tumors occurred primarily in the meninges and were common among animals inoculated perinatally but were rare among animals inoculated as adults. No neuronal tumors were encountered even among rats inoculated as early as 16 days of gestation."} {"id": "PMID:166147", "title": "Herpes simplex virus encephalitis in suckling mice: ultrastructural studies of virus replication.", "content": "Ultrastructural studies concerning the replication and release of a neuro-adapted strain of herpes simplex virus were carried out on acutely encephalitic mice. It was found that envelopment of nucleocapsid particles at the nuclear membrane of brain cells was inefficient, resulting in accumulation of unenveloped nucleocapsids in the cell cytoplasm. These nucleocapsids were associated with arrays of microtubules within cytoplasmic processes. Enveloped particles were rarely present in tissur spaces. Those that were seen appeared to be in a state of disintegration. This replication process of herpes simplex virus in the murine encephalitis model differs from that observed in tissue culture cells. The implications of these differences are discussed.", "contents": "Herpes simplex virus encephalitis in suckling mice: ultrastructural studies of virus replication. Ultrastructural studies concerning the replication and release of a neuro-adapted strain of herpes simplex virus were carried out on acutely encephalitic mice. It was found that envelopment of nucleocapsid particles at the nuclear membrane of brain cells was inefficient, resulting in accumulation of unenveloped nucleocapsids in the cell cytoplasm. These nucleocapsids were associated with arrays of microtubules within cytoplasmic processes. Enveloped particles were rarely present in tissur spaces. Those that were seen appeared to be in a state of disintegration. This replication process of herpes simplex virus in the murine encephalitis model differs from that observed in tissue culture cells. The implications of these differences are discussed."} {"id": "PMID:166148", "title": "Ultrastructure of the terminals of an identified dopamine-containing neurone markedby intracellular injection of radioactive dopamine.", "content": "The terminal processes of an identified dopamine-containing neurone in the central nervous system of the water snail were located for study with the electron microscope. This was achieved by intracellular injection of 3-H-dopamine followed by light and electron microscope autoradiography. The neurone showed extensive branching in ganglia whereprevious electrophysiological work had shown the presence of postsynaptic neurones. The terminal processes in these ganglia contained dense-cored vesicles of 50-250 nm diametersimilar to those in the perikaryon. Vesicles were found in large numbers in certain lacalized regions which may be synaptic terminals. The vesicles, which appear to take updopamine, tended to be smaller in the presumed terminal regions than in the preterminals and the perikaryon. No membrane specializations associated with typical synapses were observed.", "contents": "Ultrastructure of the terminals of an identified dopamine-containing neurone markedby intracellular injection of radioactive dopamine. The terminal processes of an identified dopamine-containing neurone in the central nervous system of the water snail were located for study with the electron microscope. This was achieved by intracellular injection of 3-H-dopamine followed by light and electron microscope autoradiography. The neurone showed extensive branching in ganglia whereprevious electrophysiological work had shown the presence of postsynaptic neurones. The terminal processes in these ganglia contained dense-cored vesicles of 50-250 nm diametersimilar to those in the perikaryon. Vesicles were found in large numbers in certain lacalized regions which may be synaptic terminals. The vesicles, which appear to take updopamine, tended to be smaller in the presumed terminal regions than in the preterminals and the perikaryon. No membrane specializations associated with typical synapses were observed."} {"id": "PMID:166149", "title": "Possible intervention of insulin, cyclic AMP, and glucocorticoids in protein-sparing action of dietary carbohydrate in rats.", "content": "The present study was carried out to examine the possible intervention of some hormones in the \"protein-sparing/actions of dietary carbohydrate and fat. Administration of either a carbohydrate meal or a fat meal to fasted rats caused a reduction in the urinary output of urea and total nitrogen with a concomitant decrease in rate of urogenesis in liver. as well as the activities of some amino acid-catabolizing enzymes in liver. The sparing action of carbohydrate but not that of fat was abolished in alloxan-diabetic rats. Feeding rats a carbohydrate meal caused a marked reduction in the amount of cyclic AMP in liver. The change was coincident with a reduction in the level of plasma urea and the urinary output of urea and total nitorgen. Administration of dibutyryl cyclic AMP abolished the carbohydrate-induced depression of urinary output of urea and total nitrogen as well as partially the activity of serine dehydratase in liver. Feeding a carbohydrate meal resulted in a significant reduction in the level of corticosterone in plasma. However, the possible intervention of glucocorticoids in the protein-sparing action of carbohydrate was ruled out inasmuch as the action of carbohydrate was also observed in the adrenalectomized rats. The overall results suggest that the protein-sparing action of dietary carbohydrate may be exerted in a different fashion from that of fat, that is, through depression of cyclic AMP in liver and thus the reduction of the degradation of amino acids in liver", "contents": "Possible intervention of insulin, cyclic AMP, and glucocorticoids in protein-sparing action of dietary carbohydrate in rats. The present study was carried out to examine the possible intervention of some hormones in the \"protein-sparing/actions of dietary carbohydrate and fat. Administration of either a carbohydrate meal or a fat meal to fasted rats caused a reduction in the urinary output of urea and total nitrogen with a concomitant decrease in rate of urogenesis in liver. as well as the activities of some amino acid-catabolizing enzymes in liver. The sparing action of carbohydrate but not that of fat was abolished in alloxan-diabetic rats. Feeding rats a carbohydrate meal caused a marked reduction in the amount of cyclic AMP in liver. The change was coincident with a reduction in the level of plasma urea and the urinary output of urea and total nitorgen. Administration of dibutyryl cyclic AMP abolished the carbohydrate-induced depression of urinary output of urea and total nitrogen as well as partially the activity of serine dehydratase in liver. Feeding a carbohydrate meal resulted in a significant reduction in the level of corticosterone in plasma. However, the possible intervention of glucocorticoids in the protein-sparing action of carbohydrate was ruled out inasmuch as the action of carbohydrate was also observed in the adrenalectomized rats. The overall results suggest that the protein-sparing action of dietary carbohydrate may be exerted in a different fashion from that of fat, that is, through depression of cyclic AMP in liver and thus the reduction of the degradation of amino acids in liver"} {"id": "PMID:166150", "title": "Cyclic AMP metabolism and nucleic acid content in the lymphocytes of the thymus, spleen, and lymph nodes of protein-deficient rats.", "content": "The concentration of cyclic AMP (cAMP) and its metabolites (5'-AMP and adenosine) as well as the adenyl cyclase, cAMP phosphodiesterase, and 5'-nucleotidase activities were determined in lymphocytes of thymus, spleen, and lymph nodes of control and protein-deficient rats. The values of these parameters, when expressed as per milligran DNA and as per 10-8 cells, but not always when expressed as per milligran protein, were much lower in the thymus as compared with the spleen and the lymph nodes in the control rats. The protein-deficient diet increased the nucleotide concentrations in the thymus and spleen lymphocytes on a per milligram DNA basis except those of thymic cAMP, which did not change. The same diet also increased the activities of the enzymes involved in the cAMP metabolism in thymic, splenic, and lymph node lymphocytes. Such a peculiarity could be related to the reduction of the mitotic activity of lymphocytes caused by protein deficiency since an inverse relationship has been reported between this activity and the synthesis of cAMP. On the other hand, it was noted that purified lymphocyte suspensions contained paradoxically higher amounts per cell of DNA, RNA, and protein in the thymus, spleen, and lymph nodes of protein-deficient rats as compared with those of the control rats. However, when the cell preparations were not purified, only the lymph node cells displayed a strong increase in their DNA content. Prolongation of the S phase of the cell cycle in these lymphocytes is suggested.", "contents": "Cyclic AMP metabolism and nucleic acid content in the lymphocytes of the thymus, spleen, and lymph nodes of protein-deficient rats. The concentration of cyclic AMP (cAMP) and its metabolites (5'-AMP and adenosine) as well as the adenyl cyclase, cAMP phosphodiesterase, and 5'-nucleotidase activities were determined in lymphocytes of thymus, spleen, and lymph nodes of control and protein-deficient rats. The values of these parameters, when expressed as per milligran DNA and as per 10-8 cells, but not always when expressed as per milligran protein, were much lower in the thymus as compared with the spleen and the lymph nodes in the control rats. The protein-deficient diet increased the nucleotide concentrations in the thymus and spleen lymphocytes on a per milligram DNA basis except those of thymic cAMP, which did not change. The same diet also increased the activities of the enzymes involved in the cAMP metabolism in thymic, splenic, and lymph node lymphocytes. Such a peculiarity could be related to the reduction of the mitotic activity of lymphocytes caused by protein deficiency since an inverse relationship has been reported between this activity and the synthesis of cAMP. On the other hand, it was noted that purified lymphocyte suspensions contained paradoxically higher amounts per cell of DNA, RNA, and protein in the thymus, spleen, and lymph nodes of protein-deficient rats as compared with those of the control rats. However, when the cell preparations were not purified, only the lymph node cells displayed a strong increase in their DNA content. Prolongation of the S phase of the cell cycle in these lymphocytes is suggested."} {"id": "PMID:166155", "title": "Timed-release depot for anticancer agents.", "content": "The timed-release of anticancer agents from composities with poly (lactic acid) was studied in rats. In the case of cyclophosphamide-poly (lactic acid) composites, 67% of the administered dose was released within 34 days. With cis-dichlorodiammineplatinum (II), the amount of drug released was only 9.3% within the same period. This difference might be attributed to the different solubilities of these two drugs in the polymer. Electron spectroscopy chemical analysis, a new tool, was used to investigate the extent of diffusion of drugs in polymer films.", "contents": "Timed-release depot for anticancer agents. The timed-release of anticancer agents from composities with poly (lactic acid) was studied in rats. In the case of cyclophosphamide-poly (lactic acid) composites, 67% of the administered dose was released within 34 days. With cis-dichlorodiammineplatinum (II), the amount of drug released was only 9.3% within the same period. This difference might be attributed to the different solubilities of these two drugs in the polymer. Electron spectroscopy chemical analysis, a new tool, was used to investigate the extent of diffusion of drugs in polymer films."} {"id": "PMID:166156", "title": "Quantitative GLC determination of conjugated estrogens in raw materials and finished dosage forms.", "content": "A GLC method is described for the quantitative analysis of conjugated estrogens. The procedure was used for the analysis of various estrogen mixtures obtained from formulations containing estrogen sodium sulfate salts. The method involves slurrying or dissolving a portion of the formulation pH 5.2 buffer, hydrolysis with sulfatase enzyme, extraction with ethylene dichloride, anf finally, GLC separation and quantitation of the corresponding trimethylsilyl ethers on a 2.5% diethylene glycol succinate column.", "contents": "Quantitative GLC determination of conjugated estrogens in raw materials and finished dosage forms. A GLC method is described for the quantitative analysis of conjugated estrogens. The procedure was used for the analysis of various estrogen mixtures obtained from formulations containing estrogen sodium sulfate salts. The method involves slurrying or dissolving a portion of the formulation pH 5.2 buffer, hydrolysis with sulfatase enzyme, extraction with ethylene dichloride, anf finally, GLC separation and quantitation of the corresponding trimethylsilyl ethers on a 2.5% diethylene glycol succinate column."} {"id": "PMID:166157", "title": "Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate.", "content": "The effects of several cyclic nucleotide analogs and of phosphodiesterase inhibitors on the release of norepinephrine (NE) and dopamine-beta-hydroxylase activity (DBH) by electrical stimulation were studied in the isolated, perfused cat spleen. N-6-butyryl-3',5'-adenosine monophosphate (mbcAMP), 8-methylthio-3',5'-adenosine monophosphate, 8-bromo-3',5'-guanosine monophosphate (8-Br-cGMP) and two potent phosphodiesterase inhibitors: 1-methyl-3-isobutylxanthine and 4-(3-butoxy-4-methoxy-benzyl)-2-imidazolidinone (Ro 20-1724) enhanced the overflow of NE and total H and reduced pressure responses elicited by nerve stimulation. A concomitant outflow of DBH activity was observed in the presence of mbcAMP, 8-Br-cGMP or Ro 20-1724. Synergistic effects on the nerve stimulation-mediated overflow of NE and DBH were obtained with low concentratons of Ro 20-1724 and mbcAMP (5 muM). Adenosine 5'-monophosphate produced a very slight increase in nerve stimulated release of NE and DBH activity in concentrations which inhibited pressor responses considerably. cAMP produced slight inhibition of pressure responses but failed to influence the release of either NE or DBH activity during nerve stimulation. In contrast to the enhanced overflow of NE and DBH activity induced by nerve stimulation, with the exception of Ro 20-1724, the spontaneous release of these substances was not modified by any of the cyclic nucleotide analogs or phosphodiesterase inhibitors examined. This effect of Ro 20-1724 can probably be explained by the ability of this compound to inhibit the activity of monoamine oxidase and therefore reduce the formation of deaminated metabolites. The present results suggest that cyclic nucleotides are not directly responsible for the release of the adrenergic neurotransmitter, but may facilitate the normal process of release by nerve stimulation. Phentolamine, a blocker of the alpha adrenergic receptors, produced a marked increase in the nerve stimulation-mediated overflow of NE, total H and DBH activity and inhibited pressure responses. This effect was several times greater than that produced by either cyclic nucleotide analogs or phosphodiesterase inhibitors. In addition, the effect of phentolamine was not modified by prior treatment with 1-methyl-3-isobutylxanthine or Ro 20-1724, suggesting that the effect of phentolamine is not related to its ability to inhibit phosphodiesterase and is probably not mediated via an increase in cAMP.", "contents": "Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate. The effects of several cyclic nucleotide analogs and of phosphodiesterase inhibitors on the release of norepinephrine (NE) and dopamine-beta-hydroxylase activity (DBH) by electrical stimulation were studied in the isolated, perfused cat spleen. N-6-butyryl-3',5'-adenosine monophosphate (mbcAMP), 8-methylthio-3',5'-adenosine monophosphate, 8-bromo-3',5'-guanosine monophosphate (8-Br-cGMP) and two potent phosphodiesterase inhibitors: 1-methyl-3-isobutylxanthine and 4-(3-butoxy-4-methoxy-benzyl)-2-imidazolidinone (Ro 20-1724) enhanced the overflow of NE and total H and reduced pressure responses elicited by nerve stimulation. A concomitant outflow of DBH activity was observed in the presence of mbcAMP, 8-Br-cGMP or Ro 20-1724. Synergistic effects on the nerve stimulation-mediated overflow of NE and DBH were obtained with low concentratons of Ro 20-1724 and mbcAMP (5 muM). Adenosine 5'-monophosphate produced a very slight increase in nerve stimulated release of NE and DBH activity in concentrations which inhibited pressor responses considerably. cAMP produced slight inhibition of pressure responses but failed to influence the release of either NE or DBH activity during nerve stimulation. In contrast to the enhanced overflow of NE and DBH activity induced by nerve stimulation, with the exception of Ro 20-1724, the spontaneous release of these substances was not modified by any of the cyclic nucleotide analogs or phosphodiesterase inhibitors examined. This effect of Ro 20-1724 can probably be explained by the ability of this compound to inhibit the activity of monoamine oxidase and therefore reduce the formation of deaminated metabolites. The present results suggest that cyclic nucleotides are not directly responsible for the release of the adrenergic neurotransmitter, but may facilitate the normal process of release by nerve stimulation. Phentolamine, a blocker of the alpha adrenergic receptors, produced a marked increase in the nerve stimulation-mediated overflow of NE, total H and DBH activity and inhibited pressure responses. This effect was several times greater than that produced by either cyclic nucleotide analogs or phosphodiesterase inhibitors. In addition, the effect of phentolamine was not modified by prior treatment with 1-methyl-3-isobutylxanthine or Ro 20-1724, suggesting that the effect of phentolamine is not related to its ability to inhibit phosphodiesterase and is probably not mediated via an increase in cAMP."} {"id": "PMID:166158", "title": "Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment.", "content": "Male CF-1 mice were treated for 14 days with diets containing haloperidol, thioridazine HCl and 4'-fluoro-4[[4-(p-fluorophenyl)-4-methoxycyclohexyl]-amino]-butyrophenone HCl (U35,777A). At various times during and after neuroleptic treatment, spontaneous and d-amphetamine-stimulated motor activity were measured. Two days after cessation of treatment, the mice displayed enhanced spontaneous and d-amphetamine-stimulated motor activity. This effect was no longer apparent 9 days after neuroleptic intake was terminated. With a quantal test based on the climbing activity induced by apomorphine, it was determined that mice were also supersensitive to apomorphine at 2 days but not 9 days after withdrawal from chronic haloperidol. In an attempt to correlate this supersensitivity to a biochemical parameter related to receptor function, dopamine-stimulated adenyl cyclase activity was assayed in striatal homogenates of mice 2 days after haloperidol withdrawal. No alteration in this parameter was observed. Likewise, the ability of apomorphine to elevate striatal cyclic adenosine monophosphate concentrations in vivo was unaltered by withdrawal from chronic haloperidol. Chronic treatment with neuroleptics results in a brief supersensitivity to dopaminergic agents. This effect does not appear to be accompanied by increases in dopamine-stimulated adenyl cyclase activity in the corpus striatum.", "contents": "Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment. Male CF-1 mice were treated for 14 days with diets containing haloperidol, thioridazine HCl and 4'-fluoro-4[[4-(p-fluorophenyl)-4-methoxycyclohexyl]-amino]-butyrophenone HCl (U35,777A). At various times during and after neuroleptic treatment, spontaneous and d-amphetamine-stimulated motor activity were measured. Two days after cessation of treatment, the mice displayed enhanced spontaneous and d-amphetamine-stimulated motor activity. This effect was no longer apparent 9 days after neuroleptic intake was terminated. With a quantal test based on the climbing activity induced by apomorphine, it was determined that mice were also supersensitive to apomorphine at 2 days but not 9 days after withdrawal from chronic haloperidol. In an attempt to correlate this supersensitivity to a biochemical parameter related to receptor function, dopamine-stimulated adenyl cyclase activity was assayed in striatal homogenates of mice 2 days after haloperidol withdrawal. No alteration in this parameter was observed. Likewise, the ability of apomorphine to elevate striatal cyclic adenosine monophosphate concentrations in vivo was unaltered by withdrawal from chronic haloperidol. Chronic treatment with neuroleptics results in a brief supersensitivity to dopaminergic agents. This effect does not appear to be accompanied by increases in dopamine-stimulated adenyl cyclase activity in the corpus striatum."} {"id": "PMID:166159", "title": "Increased extrajunctional acetylcholine sensitivity produced by chronic acetylcholine sensitivity produced by chronic post-synaptic neuromuscular blockade.", "content": "1. Anaesthetized rats were paralysed for periods of up to 3 days by chronic administration of D-tubocurarine (DTC), succinylcholine or alpha-bungarotoxin. 2. After 3 days of treatment with DTC, the phrenic nerve remained active. Neuromuscular transmission and spontaneous miniature end-plate potentials (m.e.p.p.s) were restored after removal of the DTC. Resting potentials and input resistances of muscle fibres that had been paralysed for 3 days were similar to those in denervated fibers. 3. Chronic neuromuscular blockade increased the binding of [125-I]-alpha-bungarotoxin by extrajunctional regions of muscle. The time course of the increase was similar to that seen after denervation. Binding to muscles from animals that were anaesthetized and respirated, but not paralysed, was not increased. 4. Three days of paralysis increased the sensitivity of the extrajunctional muscle membrane to acetylcholine (ACh) applied by iontophoresis. 5. Approximately the same proportion of muscle fibres from muscles paralysed for 3 days gave overshooting action potentials in the presence of tetrodotoxin 10-minus 6 g/ml. as did fibres form muscles denervated for 3 days. 6. Chronic paralysis did not change the accumulation of acetylcholinesterase above a ligation in the sciatic nerve. 7. These results are consistent with the idea that extrajunctional ACh sensitivity is normally controlled by muscle activity.", "contents": "Increased extrajunctional acetylcholine sensitivity produced by chronic acetylcholine sensitivity produced by chronic post-synaptic neuromuscular blockade. 1. Anaesthetized rats were paralysed for periods of up to 3 days by chronic administration of D-tubocurarine (DTC), succinylcholine or alpha-bungarotoxin. 2. After 3 days of treatment with DTC, the phrenic nerve remained active. Neuromuscular transmission and spontaneous miniature end-plate potentials (m.e.p.p.s) were restored after removal of the DTC. Resting potentials and input resistances of muscle fibres that had been paralysed for 3 days were similar to those in denervated fibers. 3. Chronic neuromuscular blockade increased the binding of [125-I]-alpha-bungarotoxin by extrajunctional regions of muscle. The time course of the increase was similar to that seen after denervation. Binding to muscles from animals that were anaesthetized and respirated, but not paralysed, was not increased. 4. Three days of paralysis increased the sensitivity of the extrajunctional muscle membrane to acetylcholine (ACh) applied by iontophoresis. 5. Approximately the same proportion of muscle fibres from muscles paralysed for 3 days gave overshooting action potentials in the presence of tetrodotoxin 10-minus 6 g/ml. as did fibres form muscles denervated for 3 days. 6. Chronic paralysis did not change the accumulation of acetylcholinesterase above a ligation in the sciatic nerve. 7. These results are consistent with the idea that extrajunctional ACh sensitivity is normally controlled by muscle activity."} {"id": "PMID:166160", "title": "The distribution of acetylcholine sensitivity at the post-synaptic membrane of vertebrate skeletal twitch muscles: iontophoretic mapping in the micron range.", "content": "1. The distribution of acetylcholine (ACh) sensitivity was mapped in skeletal twitch muscles of the snake, frog and mudpuppy with iontophoretic methods that provide a resolution in the mum range. 2. The preparations were thin sheets of muscle fibres that were viewed with Nomarski optics, giving sharp definition of cellular detail. The muscles in the snake were especially suitable. Their motor nerves terminate in a compact cluster of synaptic boutons that rest in distinct craters on the muscle surface. After treatment with collagenase the motor nerve and its terminal boutons can be removed, exposing the subsynaptic membrane in the craters. 3. The slopes of dose-response curves obtained by iontophoretic application of ACh were expressed in mV/nC and used as an index of ACh sensitivity. The areas of highest sensitivity, tested either with the terminals in place or removed, were those immediately under the presynaptic terminals. The greatest subsynaptic sensitivities were about 5000 mV/nC, and the time course of the potentials caused by ACh released iontophoretically closely matched that of synaptic potentials set up by ACh released by the nerve. 4. The sensitivity of the extrasynaptic surface less than 2 mum away was at least 50 times lower than that of the subsynaptic membrane. The low extrasynaptic sensitivity declined still further at greater distances. 5. Acetylcholinesterase was shown physiologically to be confined to subsynaptic areas. No activity of the enzyme was detected in extrasynaptic areas beyond about 2 mum from the edge of the synapse. 6. The confinement of high densities of receptors and of acetylcholinesterase to the subsynaptic membrane in muscles is also a feature in parasympathetic neurones. It is suggested that similar specialization may be a widespread property of neurones with chemical synapses.", "contents": "The distribution of acetylcholine sensitivity at the post-synaptic membrane of vertebrate skeletal twitch muscles: iontophoretic mapping in the micron range. 1. The distribution of acetylcholine (ACh) sensitivity was mapped in skeletal twitch muscles of the snake, frog and mudpuppy with iontophoretic methods that provide a resolution in the mum range. 2. The preparations were thin sheets of muscle fibres that were viewed with Nomarski optics, giving sharp definition of cellular detail. The muscles in the snake were especially suitable. Their motor nerves terminate in a compact cluster of synaptic boutons that rest in distinct craters on the muscle surface. After treatment with collagenase the motor nerve and its terminal boutons can be removed, exposing the subsynaptic membrane in the craters. 3. The slopes of dose-response curves obtained by iontophoretic application of ACh were expressed in mV/nC and used as an index of ACh sensitivity. The areas of highest sensitivity, tested either with the terminals in place or removed, were those immediately under the presynaptic terminals. The greatest subsynaptic sensitivities were about 5000 mV/nC, and the time course of the potentials caused by ACh released iontophoretically closely matched that of synaptic potentials set up by ACh released by the nerve. 4. The sensitivity of the extrasynaptic surface less than 2 mum away was at least 50 times lower than that of the subsynaptic membrane. The low extrasynaptic sensitivity declined still further at greater distances. 5. Acetylcholinesterase was shown physiologically to be confined to subsynaptic areas. No activity of the enzyme was detected in extrasynaptic areas beyond about 2 mum from the edge of the synapse. 6. The confinement of high densities of receptors and of acetylcholinesterase to the subsynaptic membrane in muscles is also a feature in parasympathetic neurones. It is suggested that similar specialization may be a widespread property of neurones with chemical synapses."} {"id": "PMID:166161", "title": "Active chloride secretion by in vitro guinea-pig seminal vesicle and its possible relation to vesicular function in vivo.", "content": "1. The guinea-pig seminal vesicle in vivo is characterized by a transmural electrical potential difference of approximately 11 mV with the lumen electrically negative with respect to the interstitial fluid. The concentrations of Na, Cl and K in the vesicular fluid are 13, 15, and 0-4 mM, respectively. 2. When mounted as a flat sheet in a short-circuit apparatus, guinea-pig seminal vesicles initially undergo a decline in the transmural electrical potential difference and short-circuit current ('low phase') followed by a spontaneous increase in these parameters ('high phase'). 3. During the low phase, net C1 movements across the tissue do not differ significantly from zero, and there is a small 'residual' current that is unaccounted for. 4. During the high phase, there is a significant active C1 secretion into the mucosal solution, not detectable net movement of Na and an unaccounted for or 'residual' current that is equal to that found in the low phase. 5. Theophylline, dibutyryl-3'-5' cyclic adenosinemonophosphate,prostaglandin E1 and prostaglandin F2alpha markedly stimulate the transmural electrical potential difference and short-circuit current during the low phase, but have no effect when added to the bathing solution during the high phase. 6. Diffusion potentials determined across in vitro seminal vesicles suggest that the spontaneous transmural electrical potential difference in vivo may be attributable to the large ionic asymmetries between the vesicular fluid and the plasma. 7. It is postulated that two phases are involved in the elaboration of seminal vesicular fluid. The initial phase, following emptying of the vesicle, is characterized by the secretion of electrolytes, organic molecules and water. Active C1 secretion presumably regulated by intracellular cyclic adenosinemonophosphate and/or prostaglandins may be the driving force for this initial secretion of electrolytes. Following this secretory phase, electrolytes and water are reabsorbed, thereby concentrating the organic components in the vesicular reservoir.", "contents": "Active chloride secretion by in vitro guinea-pig seminal vesicle and its possible relation to vesicular function in vivo. 1. The guinea-pig seminal vesicle in vivo is characterized by a transmural electrical potential difference of approximately 11 mV with the lumen electrically negative with respect to the interstitial fluid. The concentrations of Na, Cl and K in the vesicular fluid are 13, 15, and 0-4 mM, respectively. 2. When mounted as a flat sheet in a short-circuit apparatus, guinea-pig seminal vesicles initially undergo a decline in the transmural electrical potential difference and short-circuit current ('low phase') followed by a spontaneous increase in these parameters ('high phase'). 3. During the low phase, net C1 movements across the tissue do not differ significantly from zero, and there is a small 'residual' current that is unaccounted for. 4. During the high phase, there is a significant active C1 secretion into the mucosal solution, not detectable net movement of Na and an unaccounted for or 'residual' current that is equal to that found in the low phase. 5. Theophylline, dibutyryl-3'-5' cyclic adenosinemonophosphate,prostaglandin E1 and prostaglandin F2alpha markedly stimulate the transmural electrical potential difference and short-circuit current during the low phase, but have no effect when added to the bathing solution during the high phase. 6. Diffusion potentials determined across in vitro seminal vesicles suggest that the spontaneous transmural electrical potential difference in vivo may be attributable to the large ionic asymmetries between the vesicular fluid and the plasma. 7. It is postulated that two phases are involved in the elaboration of seminal vesicular fluid. The initial phase, following emptying of the vesicle, is characterized by the secretion of electrolytes, organic molecules and water. Active C1 secretion presumably regulated by intracellular cyclic adenosinemonophosphate and/or prostaglandins may be the driving force for this initial secretion of electrolytes. Following this secretory phase, electrolytes and water are reabsorbed, thereby concentrating the organic components in the vesicular reservoir."} {"id": "PMID:166162", "title": "On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals.", "content": "1. Conventional electrophysiological techniques were used to record from isolated rat phrenic nerve-hemidiaphragm preparations. After periods of rest (20 min) or nerve stimulation (7/sec for 20 min) the bathing medium of the preparation was removed and assayed for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) using a sensitive modification of the firefly luciferase method (Silinsky, 1974). 2. In the presence of tubocurarine and normal (2 mM) calcium, fourteen periods of nerve stimulation (eight preparations) caused the appearance of ATP and/or ADP in amounts ranging from 28 to 641 p-mole. Experiments using carbachol (30 muM or 1 mM) suggested that this nucleotide efflux was not produced by a secondary action of released acetylcholine (ACh). 3. Stimulation of isolate phrenic nerve trunks at 7/sec for 20 min did not cause the efflux of ATP or ADP. 4. In solutions of normal osmotic pressure and reduced calcium concentrations (0-1 mM or 'calcium-free'), stimulation failed to release adenine nucleotide from non-contracting preparations. 5. Diaphragms were bathed in normal calcium and indirectly stimulated at 11/sec for 80-90 min in the presence of 5 times 10-minus 5 M hemicholinium-3. After all detectable signs of ACh release were eliminated, nerve stimulation failed to release ATP or ADP. 6. These results in conjunction with experiments on the hydrolysis of exogenous ATP suggest that ATP is released from the motor nerve ending and is subsequently degraded by enzymatic activity. It is also suggested that the released nucleotide may be derived from the cholinergic vesicle.", "contents": "On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. 1. Conventional electrophysiological techniques were used to record from isolated rat phrenic nerve-hemidiaphragm preparations. After periods of rest (20 min) or nerve stimulation (7/sec for 20 min) the bathing medium of the preparation was removed and assayed for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) using a sensitive modification of the firefly luciferase method (Silinsky, 1974). 2. In the presence of tubocurarine and normal (2 mM) calcium, fourteen periods of nerve stimulation (eight preparations) caused the appearance of ATP and/or ADP in amounts ranging from 28 to 641 p-mole. Experiments using carbachol (30 muM or 1 mM) suggested that this nucleotide efflux was not produced by a secondary action of released acetylcholine (ACh). 3. Stimulation of isolate phrenic nerve trunks at 7/sec for 20 min did not cause the efflux of ATP or ADP. 4. In solutions of normal osmotic pressure and reduced calcium concentrations (0-1 mM or 'calcium-free'), stimulation failed to release adenine nucleotide from non-contracting preparations. 5. Diaphragms were bathed in normal calcium and indirectly stimulated at 11/sec for 80-90 min in the presence of 5 times 10-minus 5 M hemicholinium-3. After all detectable signs of ACh release were eliminated, nerve stimulation failed to release ATP or ADP. 6. These results in conjunction with experiments on the hydrolysis of exogenous ATP suggest that ATP is released from the motor nerve ending and is subsequently degraded by enzymatic activity. It is also suggested that the released nucleotide may be derived from the cholinergic vesicle."} {"id": "PMID:166163", "title": "A note of the mechanism by which inhibitors of the sodium pump accelerate spontaneous release of transmitter from motor nerve terminals.", "content": "1. The actions of 0-1 mM ouabain and of K-free Ringer have been examined at the frog neuromuscular junction. 2. After a delay of more than 30 min, ouabain produces an increase in the miniature end-plate potential (m.e.p.p.) frequency. This increase occurs unchanged in Ca-free Ringer containing 1 mM-EGTA and is therefore unlikely to be due to an entry of Ca into the motor nerve terminals. 3. If the nerve to the preparation is stimulated repetitively in Ca-free Ringer containing 0-1 mM ouabain and 1 mM-EGTA the response of the m.e.p.p. frequency depends on the timing of the tetanus relative to the beginning of the ouabain treatment. 4. During the first 30 min of exposure to ouabain, the tetanus produces a small, transient increase in the m.e.p.p. frequency similar to that which occurs before ouabain is present. After about 30 min the same tetanus produces large, irreversible increases in the m.e.p.p. frequency. 5. Superfusion of an end-plate with K-free Ringer causes an immediate exponential rise in the m.e.p.p. frequency that is unaffected by the presence of external Ca ions. On replacing the normal K of the Ringer (2 mM) the m.e.p.p. frequency recovers quickly to its original value. 6. Late in an exposure to 0-1 mM ouabain the m.e.p.p. frequency becomes extremely sensitive to changes in the external Na concentration, [Na]o. Reducing [Na]o increases the m.e.p.p. frequency. The sensitivity to [Na]o is independent of external Ca ions or whether the isotonic substitute for NaCl is LiCl or sucrose. 7. It is suggested that the spontaneous release of transmitter is facilitated, in some way, by the changes in the monovalent cation content of the nerve terminals that result from blocking the Na-K exchange pump. The Na sensitivity of the m.e.p.p. frequency that develops simultaneously can be explained if a Na-dependent Ca efflux system is present in the membrane of the presynaptic terminals.", "contents": "A note of the mechanism by which inhibitors of the sodium pump accelerate spontaneous release of transmitter from motor nerve terminals. 1. The actions of 0-1 mM ouabain and of K-free Ringer have been examined at the frog neuromuscular junction. 2. After a delay of more than 30 min, ouabain produces an increase in the miniature end-plate potential (m.e.p.p.) frequency. This increase occurs unchanged in Ca-free Ringer containing 1 mM-EGTA and is therefore unlikely to be due to an entry of Ca into the motor nerve terminals. 3. If the nerve to the preparation is stimulated repetitively in Ca-free Ringer containing 0-1 mM ouabain and 1 mM-EGTA the response of the m.e.p.p. frequency depends on the timing of the tetanus relative to the beginning of the ouabain treatment. 4. During the first 30 min of exposure to ouabain, the tetanus produces a small, transient increase in the m.e.p.p. frequency similar to that which occurs before ouabain is present. After about 30 min the same tetanus produces large, irreversible increases in the m.e.p.p. frequency. 5. Superfusion of an end-plate with K-free Ringer causes an immediate exponential rise in the m.e.p.p. frequency that is unaffected by the presence of external Ca ions. On replacing the normal K of the Ringer (2 mM) the m.e.p.p. frequency recovers quickly to its original value. 6. Late in an exposure to 0-1 mM ouabain the m.e.p.p. frequency becomes extremely sensitive to changes in the external Na concentration, [Na]o. Reducing [Na]o increases the m.e.p.p. frequency. The sensitivity to [Na]o is independent of external Ca ions or whether the isotonic substitute for NaCl is LiCl or sucrose. 7. It is suggested that the spontaneous release of transmitter is facilitated, in some way, by the changes in the monovalent cation content of the nerve terminals that result from blocking the Na-K exchange pump. The Na sensitivity of the m.e.p.p. frequency that develops simultaneously can be explained if a Na-dependent Ca efflux system is present in the membrane of the presynaptic terminals."} {"id": "PMID:166167", "title": "The relationship of adenosine triphosphatase activity to tension and power output of insect flight muscle.", "content": "1. On a simple model of actomyosin interaction, the tension cost (ATP hydrolysed/unit tension) and the frequency of low amplitude oscillation optimum for work production are both determined by the rate of detachment from the actin filament of the myosin crossbridge. To test this model, the two parameters were measured under different conditions using glycerol-extracted Lethocerus cordofanus dorsal longitudinal flight muscle fibres. 2. The ATPase activity of the static muscle rose by an amount approximately proportional to the rise in tension as the muscle was stretched. 3. When the muscle fibres were sinusoidally oscillated at 5-10 Hz by 2% of their resting length they produced a large amount of mechanical power and hydrolysed approximately twice as much ATP per unit mean tension as they did when static. The ATPase activity was linearly related to the mean tension during oscillation. 4. The experiments were repeated at temperatures between 12 and 30 degrees C and the tension cost and the optimal frequency of oscillation of the fibres were found to rise with temperature. 5. Removal of phosphate from the incubating medium reduced both the tension cost and the optimal working frequency. Addition of pyrophosphate or sulphate reduced both parameters still further. 6. From these results the tension cost of static muscle was shown to be proportional to its optimal working frequency. 7. ATPase activity rose monotonically with power production at work-producing frequencies and at moderate degrees of stretch. A high absolute efficiency was found under a wide range of conditions. 8. The proportionality between tension cost and optimal frequency is evidence for the proposed model of actomyosin interaction.", "contents": "The relationship of adenosine triphosphatase activity to tension and power output of insect flight muscle. 1. On a simple model of actomyosin interaction, the tension cost (ATP hydrolysed/unit tension) and the frequency of low amplitude oscillation optimum for work production are both determined by the rate of detachment from the actin filament of the myosin crossbridge. To test this model, the two parameters were measured under different conditions using glycerol-extracted Lethocerus cordofanus dorsal longitudinal flight muscle fibres. 2. The ATPase activity of the static muscle rose by an amount approximately proportional to the rise in tension as the muscle was stretched. 3. When the muscle fibres were sinusoidally oscillated at 5-10 Hz by 2% of their resting length they produced a large amount of mechanical power and hydrolysed approximately twice as much ATP per unit mean tension as they did when static. The ATPase activity was linearly related to the mean tension during oscillation. 4. The experiments were repeated at temperatures between 12 and 30 degrees C and the tension cost and the optimal frequency of oscillation of the fibres were found to rise with temperature. 5. Removal of phosphate from the incubating medium reduced both the tension cost and the optimal working frequency. Addition of pyrophosphate or sulphate reduced both parameters still further. 6. From these results the tension cost of static muscle was shown to be proportional to its optimal working frequency. 7. ATPase activity rose monotonically with power production at work-producing frequencies and at moderate degrees of stretch. A high absolute efficiency was found under a wide range of conditions. 8. The proportionality between tension cost and optimal frequency is evidence for the proposed model of actomyosin interaction."} {"id": "PMID:166169", "title": "Behavior modification approach in a partial day treatment center.", "content": "Since the beginning of the program in September 1970, we have found that a combined behavioral program of individual therapy, home intervention, and group therapy to be the most effective for maintaining a person in his community. In addition, we have not seen a need for a full eight-hour day in the clinic. Rather, we operate on the principle that it is more adaptive to keep a patient functioning in the community (natural environment) with support from us. For the extremely or severely disorganized person, we have found the application of behavior modification principles to be the most useful in the terms of establishing and maintaining adaptive behaviors, of interruptin and decreasing maladaptive behaviors and of offering support and guidance (generalization) to patients and families. We have also increased the amount of individual therapy and intensified the home intervention program. These changes have been based upon subjective data as well as objective data (change in patient behavior while receiving and following a particular mode of therapy). The program has undergone many changes since its inception. We have found the behavior modification modality to be effective for establishing a program that patients can generalize to their community setting. Our constant thrust is to utilize already existing agencies in the community and to optimally assist the patient so that he may remain in his community. We have gone from an eclectic program to a systematic behavior modification program. The present behavioral program has been demonstrated to be an effective modality for the training of personnel. We are grateful to our staff for their cooperation and suggestions in making the program successful. In addition, we are indebted to our late Director, Curtis W; Gifford--a loyal and dedicated friend. We particularly appreciate his administrative skills and encouragement in developing an autonomous program.", "contents": "Behavior modification approach in a partial day treatment center. Since the beginning of the program in September 1970, we have found that a combined behavioral program of individual therapy, home intervention, and group therapy to be the most effective for maintaining a person in his community. In addition, we have not seen a need for a full eight-hour day in the clinic. Rather, we operate on the principle that it is more adaptive to keep a patient functioning in the community (natural environment) with support from us. For the extremely or severely disorganized person, we have found the application of behavior modification principles to be the most useful in the terms of establishing and maintaining adaptive behaviors, of interruptin and decreasing maladaptive behaviors and of offering support and guidance (generalization) to patients and families. We have also increased the amount of individual therapy and intensified the home intervention program. These changes have been based upon subjective data as well as objective data (change in patient behavior while receiving and following a particular mode of therapy). The program has undergone many changes since its inception. We have found the behavior modification modality to be effective for establishing a program that patients can generalize to their community setting. Our constant thrust is to utilize already existing agencies in the community and to optimally assist the patient so that he may remain in his community. We have gone from an eclectic program to a systematic behavior modification program. The present behavioral program has been demonstrated to be an effective modality for the training of personnel. We are grateful to our staff for their cooperation and suggestions in making the program successful. In addition, we are indebted to our late Director, Curtis W; Gifford--a loyal and dedicated friend. We particularly appreciate his administrative skills and encouragement in developing an autonomous program."} {"id": "PMID:166176", "title": "Accountability: a right of the rape victim.", "content": "Accountability by the professional is especially important in a crisis situation. Rape is experienced by victims as a life threatening situation and it thus triggers an acute stress reaction which requires them to go through a long-term reorganization process. As a crisis situation, it makes them hypersensitive to the attitudes of those people to whom they turn for help and assistance. Clients--in this case rape victims--benefit when professionals are careful to be accountable to them. The victim counselors defined and redefined their role to the victims through their work with the victim as well as explaninig the services they could provide. In reviewing the reactions of 146 victims to treatment by police, hospital, and counselors, one theme emerged again and again: clients want explanation from professionals about role expectations and about procedures that are to be done.", "contents": "Accountability: a right of the rape victim. Accountability by the professional is especially important in a crisis situation. Rape is experienced by victims as a life threatening situation and it thus triggers an acute stress reaction which requires them to go through a long-term reorganization process. As a crisis situation, it makes them hypersensitive to the attitudes of those people to whom they turn for help and assistance. Clients--in this case rape victims--benefit when professionals are careful to be accountable to them. The victim counselors defined and redefined their role to the victims through their work with the victim as well as explaninig the services they could provide. In reviewing the reactions of 146 victims to treatment by police, hospital, and counselors, one theme emerged again and again: clients want explanation from professionals about role expectations and about procedures that are to be done."} {"id": "PMID:166179", "title": "Tactics for counteracting staff apathy and hopelessness on a psychiatric unit.", "content": "In summary, then, the five following tactics are minimally demanding, and can provide high rewards in the battle against apathy and hopelessness on a psychiatric ward. 1. Identifying social system mechanisms. 2. Validating perceptions of ward happenings with a trusted other. 3. Giving (and hopefully receiving) \"informational-support.\" 4. Using physical presence or being highly visible. 5. Chatting informally with other staff members.", "contents": "Tactics for counteracting staff apathy and hopelessness on a psychiatric unit. In summary, then, the five following tactics are minimally demanding, and can provide high rewards in the battle against apathy and hopelessness on a psychiatric ward. 1. Identifying social system mechanisms. 2. Validating perceptions of ward happenings with a trusted other. 3. Giving (and hopefully receiving) \"informational-support.\" 4. Using physical presence or being highly visible. 5. Chatting informally with other staff members."} {"id": "PMID:166178", "title": "Nutritional concerns of addicts in treatment.", "content": "Some of the subcultural phenomena affecting diet patterns of methadone patients have been utilized to derive principles of treatment intervention. Attitudes and values related to time, treatment personnel, and group identification are important cultural determinants of beliefs and behaviors affecting nutrition. The proposed program of intervention is based on ethnographic observations. This suggested program emphasized the inclusion of cultural identity, sense of uniqueness and group information sharing and reinforcement. These characteristics are valued highly in the informants' subcultural group, and are important components of acceptable proprosals for change within this group.", "contents": "Nutritional concerns of addicts in treatment. Some of the subcultural phenomena affecting diet patterns of methadone patients have been utilized to derive principles of treatment intervention. Attitudes and values related to time, treatment personnel, and group identification are important cultural determinants of beliefs and behaviors affecting nutrition. The proposed program of intervention is based on ethnographic observations. This suggested program emphasized the inclusion of cultural identity, sense of uniqueness and group information sharing and reinforcement. These characteristics are valued highly in the informants' subcultural group, and are important components of acceptable proprosals for change within this group."} {"id": "PMID:166185", "title": "Chemotherapeutic nitroheterocycles. 18. 2-(5-Nitro-2-imidazolylmethylene)-1-indanones, -1-tetralones, and -acetophenones substituted by aminoalkoxy groups.", "content": "2-(5-Nitro-2-imidazolylmethylene)-1-indanones, -1-tetralones, and -acetophenones substituted by aminoalkoxy groups and related compounds (41-69, table ii) were synthesized and their antimicrobial activities were evaluated (table iii). Some of these compounds (e.g. 47, 52, and 59) suprisingly exhibited a broad antibacterial spectrum including Proteus species and Pseudomonas aeruginosa. Extraordinary antitrichomonal activities could also be observed in vitro (MIC of compound 59, 0.0004 pg/ml) and six of the title compounds (48, 49, 52, 58, 64, 66) displayed in vivo activity in mice against Trichomonas vaginalis comparable to that of metronidazole (70).", "contents": "Chemotherapeutic nitroheterocycles. 18. 2-(5-Nitro-2-imidazolylmethylene)-1-indanones, -1-tetralones, and -acetophenones substituted by aminoalkoxy groups. 2-(5-Nitro-2-imidazolylmethylene)-1-indanones, -1-tetralones, and -acetophenones substituted by aminoalkoxy groups and related compounds (41-69, table ii) were synthesized and their antimicrobial activities were evaluated (table iii). Some of these compounds (e.g. 47, 52, and 59) suprisingly exhibited a broad antibacterial spectrum including Proteus species and Pseudomonas aeruginosa. Extraordinary antitrichomonal activities could also be observed in vitro (MIC of compound 59, 0.0004 pg/ml) and six of the title compounds (48, 49, 52, 58, 64, 66) displayed in vivo activity in mice against Trichomonas vaginalis comparable to that of metronidazole (70)."} {"id": "PMID:166186", "title": "Immunologic, virologic, and genetic aspects of mammary tumor virus-induced cell-surface antigens: presence of these antigens and the Thy 1.2 antigen on murine mammary gland and tumor cells.", "content": "The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain.", "contents": "Immunologic, virologic, and genetic aspects of mammary tumor virus-induced cell-surface antigens: presence of these antigens and the Thy 1.2 antigen on murine mammary gland and tumor cells. The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain."} {"id": "PMID:166187", "title": "Distribution and antibody-induced redistribution of a mammary tumor virus-induced and a normal antigen on the surface of mouse leukemia cells.", "content": "By means of the indirect membrane immunofluorescence test, the distribution and antibody-induced redistribution (patching and capping) of a mammary tumor virus-induced (MLr) and a normal (Thy 1.2) cell-surface antigen were compared on mouse thymocytes and leukemia cells (GRSL2). At 0 degrees C Thy 1.2 fluorescence was ringlike and more intense on GRSL2 cells than on thymocytes, whereas MLr fluorescence on GRLS2 cells at this temperature was patchlike and brighter than Thy 1.2 fluorescence. At 20 or 37 degrees C, capping of Thy 1.2 on both cell types was readily achieved but MLr capping occurred only in a few GRSL2 cells and was less pronounced. However, after addition of the secondary antibodies, MLr capping was markedly increased by gradual cooling of cells to about 17 degrees C. Conversely, after addition of antibodies at 0 degrees C, gradual warming of cells under the fluorescence microscope resulted in extensive capping both of MLr and Thy 1.2 at approximately 13-14 degrees C. Rapid cooling or rapid warming led to almost instantaneous capping. These results may be explained by the occurrence of phase transitions or phase separations in the particular temperature range. Another difference between capping of Thy 1.2 and MLr was that the former caps were small and eventually were endocytosed, whereas the MLr caps were large and were exfoliated from the cells.", "contents": "Distribution and antibody-induced redistribution of a mammary tumor virus-induced and a normal antigen on the surface of mouse leukemia cells. By means of the indirect membrane immunofluorescence test, the distribution and antibody-induced redistribution (patching and capping) of a mammary tumor virus-induced (MLr) and a normal (Thy 1.2) cell-surface antigen were compared on mouse thymocytes and leukemia cells (GRSL2). At 0 degrees C Thy 1.2 fluorescence was ringlike and more intense on GRSL2 cells than on thymocytes, whereas MLr fluorescence on GRLS2 cells at this temperature was patchlike and brighter than Thy 1.2 fluorescence. At 20 or 37 degrees C, capping of Thy 1.2 on both cell types was readily achieved but MLr capping occurred only in a few GRSL2 cells and was less pronounced. However, after addition of the secondary antibodies, MLr capping was markedly increased by gradual cooling of cells to about 17 degrees C. Conversely, after addition of antibodies at 0 degrees C, gradual warming of cells under the fluorescence microscope resulted in extensive capping both of MLr and Thy 1.2 at approximately 13-14 degrees C. Rapid cooling or rapid warming led to almost instantaneous capping. These results may be explained by the occurrence of phase transitions or phase separations in the particular temperature range. Another difference between capping of Thy 1.2 and MLr was that the former caps were small and eventually were endocytosed, whereas the MLr caps were large and were exfoliated from the cells."} {"id": "PMID:166188", "title": "Protective tumor immunity induced by potassium chloride extracts of guinea pig hepatomas.", "content": "Tumor-specific antigens of cells of the diethylnitrosamine-induced hepatomas in strain-2 guinea pigs were extracted with 3 M KCl. Immunization of normal animals with the extracted tumor antigens in adjuvant protected them against a subsequent challenge with viable tumor cells. Extracted tumor-specific antigens were less effective immunogens than viable tumor cells for both of two antigenically distinct lines.", "contents": "Protective tumor immunity induced by potassium chloride extracts of guinea pig hepatomas. Tumor-specific antigens of cells of the diethylnitrosamine-induced hepatomas in strain-2 guinea pigs were extracted with 3 M KCl. Immunization of normal animals with the extracted tumor antigens in adjuvant protected them against a subsequent challenge with viable tumor cells. Extracted tumor-specific antigens were less effective immunogens than viable tumor cells for both of two antigenically distinct lines."} {"id": "PMID:166189", "title": "Isolation and characterization of viruses from natural outbreaks of reticuloendotheliosis in turkeys.", "content": "We have described the in vitro isolation of type-C RNA viruses from two outbreaks of a fatal neoplastic disease in turkeys we diagnosed as reticuloendotheliosis. The virus had a density of 1.16 g/ml in sucrose gradients, had a DNA polymerase capable of using both endogenous and exogenous (synthetic) templates, and was infectious in vitro for turkey and chick cells. The culture-propagated virus was oncogenic for turkeys. The virus isolates were unrelated to avian leukosis virus and antigenically identical to reticuloendotheliosis virus (REV) strain T. Thus our studies suggested that REV is a causative agent of naturally occurring, fatal leukosis in turkeys.", "contents": "Isolation and characterization of viruses from natural outbreaks of reticuloendotheliosis in turkeys. We have described the in vitro isolation of type-C RNA viruses from two outbreaks of a fatal neoplastic disease in turkeys we diagnosed as reticuloendotheliosis. The virus had a density of 1.16 g/ml in sucrose gradients, had a DNA polymerase capable of using both endogenous and exogenous (synthetic) templates, and was infectious in vitro for turkey and chick cells. The culture-propagated virus was oncogenic for turkeys. The virus isolates were unrelated to avian leukosis virus and antigenically identical to reticuloendotheliosis virus (REV) strain T. Thus our studies suggested that REV is a causative agent of naturally occurring, fatal leukosis in turkeys."} {"id": "PMID:166190", "title": "Hormonally induced renal neoplasia in the male Syrian hamster and the inhibitory effect of 2-bromo-alpha-ergocryptine methanesulfonate.", "content": "One group of male Syrian hamsters received diethylstilbestrol (DES) over a period of 9 months. All developed widespread and severe renal tumors. Another group of male Syrian hamsters was given DES plus 2-bromo-alpha-ergocryptine methanesulfonate (CB154) over the same period. These hamsters either did not develop renal tumors or had renal tumors that were minimal in severity. DES treatment induced hyperplastic and neoplastic changes in the intermediate lobe of the pituitary glands of treated animals, increased the number of prolactin-secreting cells, and decreased the number of somatotrophin-secreting cells. Adding CB154 significantly inhibited those changes in the pituitary gland. Histopathologic and ultrastructural examinations indicated that the renal tumors were carcinomas originating from proximal convoluted tubules.", "contents": "Hormonally induced renal neoplasia in the male Syrian hamster and the inhibitory effect of 2-bromo-alpha-ergocryptine methanesulfonate. One group of male Syrian hamsters received diethylstilbestrol (DES) over a period of 9 months. All developed widespread and severe renal tumors. Another group of male Syrian hamsters was given DES plus 2-bromo-alpha-ergocryptine methanesulfonate (CB154) over the same period. These hamsters either did not develop renal tumors or had renal tumors that were minimal in severity. DES treatment induced hyperplastic and neoplastic changes in the intermediate lobe of the pituitary glands of treated animals, increased the number of prolactin-secreting cells, and decreased the number of somatotrophin-secreting cells. Adding CB154 significantly inhibited those changes in the pituitary gland. Histopathologic and ultrastructural examinations indicated that the renal tumors were carcinomas originating from proximal convoluted tubules."} {"id": "PMID:166191", "title": "Clinicopathologic characterization of Herpesvirus saimiri malignant lymphoma in New Zealand white rabbits.", "content": "Twenty-two of 39 rabbits inoculated with Herpesvirus saimiri developed malignant lymphoma and either died or were killed between 17 and 165 days after inoculation. No clinical signs were present in animals developing the disease before 46 days, but all other rabbits had a severe conjunctivitis, nasal discharge, and dyspnea resulting from a lymphocytic invasion of the ocular and nasal tissues. Four rabbits developed terminal leukemia. Pathologically, the disease resembled H. saimiri malignant lymphoma in nonhuman primates; there was extensive diffuse infiltration of most organs and tissues with either a lymphocytic or lymphoblastic infiltrate. Tumor nodules or masses seen in some forms of malignant lymphoma were not present. In contrast to nonhuman primates, all affected rabbits showed invasion of the skin of the nose and eyelids, conjunctiva, iris, ciliary body, and choroid. In 3 rabbits there was slight infiltration into the brain, not noted in nonhuman primates. The susceptibility of rabbits extended the host range of H. saimiri beyond the order Primates.", "contents": "Clinicopathologic characterization of Herpesvirus saimiri malignant lymphoma in New Zealand white rabbits. Twenty-two of 39 rabbits inoculated with Herpesvirus saimiri developed malignant lymphoma and either died or were killed between 17 and 165 days after inoculation. No clinical signs were present in animals developing the disease before 46 days, but all other rabbits had a severe conjunctivitis, nasal discharge, and dyspnea resulting from a lymphocytic invasion of the ocular and nasal tissues. Four rabbits developed terminal leukemia. Pathologically, the disease resembled H. saimiri malignant lymphoma in nonhuman primates; there was extensive diffuse infiltration of most organs and tissues with either a lymphocytic or lymphoblastic infiltrate. Tumor nodules or masses seen in some forms of malignant lymphoma were not present. In contrast to nonhuman primates, all affected rabbits showed invasion of the skin of the nose and eyelids, conjunctiva, iris, ciliary body, and choroid. In 3 rabbits there was slight infiltration into the brain, not noted in nonhuman primates. The susceptibility of rabbits extended the host range of H. saimiri beyond the order Primates."} {"id": "PMID:166193", "title": "Nuclear magnetic resonance studies of cancer. VI. Relationship among spin-lattice relaxation times, growth rate, and water content of Morris hepatomas.", "content": "Relaxation time(s) (T1), growth rates, and the water content of six Morris hepatomas, several murine tumors, and a selection of normal tissues indicated that malignant tumors did not always exhibit longer T1 values than any normal tissue, as previously suspected. This overlap raised the possibility of confusion between normal and malignant tissues studied by this method. Tissue T1 values depended primarily on the hydration of the tissue and correlated well with water content determinations. A rough correlation of T1 and water content with tumor growth rate was also observed.", "contents": "Nuclear magnetic resonance studies of cancer. VI. Relationship among spin-lattice relaxation times, growth rate, and water content of Morris hepatomas. Relaxation time(s) (T1), growth rates, and the water content of six Morris hepatomas, several murine tumors, and a selection of normal tissues indicated that malignant tumors did not always exhibit longer T1 values than any normal tissue, as previously suspected. This overlap raised the possibility of confusion between normal and malignant tissues studied by this method. Tissue T1 values depended primarily on the hydration of the tissue and correlated well with water content determinations. A rough correlation of T1 and water content with tumor growth rate was also observed."} {"id": "PMID:166192", "title": "Maturation and differentiation of B16 melanoma cells induced by theophylline treatment.", "content": "Recent studies suggested that 3',5'-cyclic AMP (CAMP) may be involved in the regulation of cell proliferation and differentiation. Theophylline, an inhibitor of cyclic nucleotide phosphodiesterase, elevated intracellular cAMP. A melanotic clone of the B16 melanoma was treated with theophylline and studied in vitro and in vivo. With 12 hours after 1.0 mM theophylline was added to growing cultures, the number of cells incorporating tritiated thymidine (3-H-TDR) and the rate of uptake of 3-H-TDR into DNA were significantly reduced. After 7 days, the number of cells in the control cultures increased twenty-four times, whereas theophylline-treated cells increased only sixfold. Compared to the controls, the theophylline-treated cells contained ten times the melanin and an elevated cAMP content. Stimulation of melanogenesis and inhibition of proliferation increased progressively with duration of exposure to theophylline. After 5 days of culture with theophylline, cells were assayed for plating efficiency in theophylline-free medium. Although the number of colony-forming cells was unaffected by previous exposure to theophylline, the colonies were composed of fewer cells inoculated into syngeneic hosts were less tumorigenic than untreated cells. However, theophylline treatment of hosts bearing B16 tumors failed to reduce the tumor growth rate, and theophylline did not potentiate the growth inhibition resulting from treatment with the synthetic polyribonucleotide, polyinosinic-polycytidylic acid.", "contents": "Maturation and differentiation of B16 melanoma cells induced by theophylline treatment. Recent studies suggested that 3',5'-cyclic AMP (CAMP) may be involved in the regulation of cell proliferation and differentiation. Theophylline, an inhibitor of cyclic nucleotide phosphodiesterase, elevated intracellular cAMP. A melanotic clone of the B16 melanoma was treated with theophylline and studied in vitro and in vivo. With 12 hours after 1.0 mM theophylline was added to growing cultures, the number of cells incorporating tritiated thymidine (3-H-TDR) and the rate of uptake of 3-H-TDR into DNA were significantly reduced. After 7 days, the number of cells in the control cultures increased twenty-four times, whereas theophylline-treated cells increased only sixfold. Compared to the controls, the theophylline-treated cells contained ten times the melanin and an elevated cAMP content. Stimulation of melanogenesis and inhibition of proliferation increased progressively with duration of exposure to theophylline. After 5 days of culture with theophylline, cells were assayed for plating efficiency in theophylline-free medium. Although the number of colony-forming cells was unaffected by previous exposure to theophylline, the colonies were composed of fewer cells inoculated into syngeneic hosts were less tumorigenic than untreated cells. However, theophylline treatment of hosts bearing B16 tumors failed to reduce the tumor growth rate, and theophylline did not potentiate the growth inhibition resulting from treatment with the synthetic polyribonucleotide, polyinosinic-polycytidylic acid."} {"id": "PMID:166194", "title": "R-type virus-like particles in avian sarcoma virus-induced rat central nervous system tumors.", "content": "Morphologically distinct virus-like particles (VLP), similar to R-type VLP, were observed by electron microscopy in experimental rat central nervous system tumors induced with the B-77-C strain of avian sarcoma virus (ASV). R-type VLP have a characteristic internal radial structure and were observed previously only in hamster cells and in an established bovine cell line. They were not observed in the B-77 ASV inoculum used to induce the rat tumors or in the B-77 induced hamster glioma cells from which the B-77 was rescued. Nevertheless, the genome of an endogenous hamster R-type particle also might have been rescued and carried in the B-77 inoculum. Alternatively, R-type VLP may exist in a number of animal species, including the rat, and may be expressed in certain conditions such as neoplastic transformation.", "contents": "R-type virus-like particles in avian sarcoma virus-induced rat central nervous system tumors. Morphologically distinct virus-like particles (VLP), similar to R-type VLP, were observed by electron microscopy in experimental rat central nervous system tumors induced with the B-77-C strain of avian sarcoma virus (ASV). R-type VLP have a characteristic internal radial structure and were observed previously only in hamster cells and in an established bovine cell line. They were not observed in the B-77 ASV inoculum used to induce the rat tumors or in the B-77 induced hamster glioma cells from which the B-77 was rescued. Nevertheless, the genome of an endogenous hamster R-type particle also might have been rescued and carried in the B-77 inoculum. Alternatively, R-type VLP may exist in a number of animal species, including the rat, and may be expressed in certain conditions such as neoplastic transformation."} {"id": "PMID:166199", "title": "Polyoma virus strain with enhanced synthesis of capsid protein.", "content": "A study of the immunochemical characteristics and the synthesis of the capsid proteins of two polyoma virus strains (3049 and 1pS) was carried out to determine the mechanism responsible for the unique accumulation of those structural polypeptides in the cytoplasm of cells infected with the 3049 strain. Antisera prepared against disaggregated virus peptides and whole virus were used to measure the quantity of virus-specific antigens in cells infected by the two strains by using an indirect radioimmunoassay technique. The 3049-infected mouse embryo cells were found to contain several-fold more antibody-binding material than those infected with the 1pS strain. Furthermore, the cytoplasmic fraction of 3049-infected cells also contained more antibody-binding activity, supporting the hypothesis that the phenotype of the 3049 virus (cytoplasmic capsid protein) was a reflection of the increased synthesis of the capsid polypeptides.", "contents": "Polyoma virus strain with enhanced synthesis of capsid protein. A study of the immunochemical characteristics and the synthesis of the capsid proteins of two polyoma virus strains (3049 and 1pS) was carried out to determine the mechanism responsible for the unique accumulation of those structural polypeptides in the cytoplasm of cells infected with the 3049 strain. Antisera prepared against disaggregated virus peptides and whole virus were used to measure the quantity of virus-specific antigens in cells infected by the two strains by using an indirect radioimmunoassay technique. The 3049-infected mouse embryo cells were found to contain several-fold more antibody-binding material than those infected with the 1pS strain. Furthermore, the cytoplasmic fraction of 3049-infected cells also contained more antibody-binding activity, supporting the hypothesis that the phenotype of the 3049 virus (cytoplasmic capsid protein) was a reflection of the increased synthesis of the capsid polypeptides."} {"id": "PMID:166200", "title": "Comparative studies on the structural phosphoproteins of mammalian type C viruses.", "content": "The major phosphoprotein common to woolly monkey sarcoma virus, gibbon ape lymphosarcoma virus, and type C viruses of the lower mammalian species (mouse, rat, cat), with the exception of the endogenous cat virus (RD-114), is the polypeptide of about 12,000 molecular weight. The protein-phosphate bond in this polypeptide of several viruses is of the phosphoserine variety excepting gibbon ape virus, which contains both phosphoserine and phosphothreonine. The primary phosphoprotein of RD-114 virus and the endogenous baboon type C virus, on the other hand, is the polypeptide of about 15,000 molecular weight which contains phosphothreonine as its phosphoamino acid. A second major phosphoprotein of molecular weight of 10,000 is detected only in viruses genetically related to rat species including those derived from the RPL cell line, from Sprague-Dawley rat embryo cells, and the Kirsten mouse sarcoma virus which was recovered from a mouse erythroblastosis virus after in vivo propagation through rat. These phosphorylated polypeptides of molecular weight 15,000, 12,000, or 10,000 are present in the virion structure in several different but nonrandom phosphorylated states.", "contents": "Comparative studies on the structural phosphoproteins of mammalian type C viruses. The major phosphoprotein common to woolly monkey sarcoma virus, gibbon ape lymphosarcoma virus, and type C viruses of the lower mammalian species (mouse, rat, cat), with the exception of the endogenous cat virus (RD-114), is the polypeptide of about 12,000 molecular weight. The protein-phosphate bond in this polypeptide of several viruses is of the phosphoserine variety excepting gibbon ape virus, which contains both phosphoserine and phosphothreonine. The primary phosphoprotein of RD-114 virus and the endogenous baboon type C virus, on the other hand, is the polypeptide of about 15,000 molecular weight which contains phosphothreonine as its phosphoamino acid. A second major phosphoprotein of molecular weight of 10,000 is detected only in viruses genetically related to rat species including those derived from the RPL cell line, from Sprague-Dawley rat embryo cells, and the Kirsten mouse sarcoma virus which was recovered from a mouse erythroblastosis virus after in vivo propagation through rat. These phosphorylated polypeptides of molecular weight 15,000, 12,000, or 10,000 are present in the virion structure in several different but nonrandom phosphorylated states."} {"id": "PMID:166201", "title": "Iodination of herpesvirus nucleic acids.", "content": "A simple method is described for the iodination of herpes simplex virus (HSV) DNA. The procedure involved synthesis of 125-I-labeled 5-iodo-dCTP which was subsequently used as a precursor for the in vitro repair synthesis of HSV DNA. Synthesis of 5-iodo-dCTP and purification from oxidation and reduction reagents, buffer salts, unreacted dCTP and Na125-I was accomplished in a single chromatographic step. It was possible to prepare 125-I-labeled HSV DNA in vitro with specific activities exceeding 10-8 counts/min/mu-g. The DNA prepared by this method reassociated with DNA extracted from HSV-infected HEp-2 cells but not with HEp-2 cell DNA. Iodinated HSV DNA was susceptible to S-1-endonuclease digestion once denatured but was resistant to digestion in the native form. This method was used to synthesize 125-I-labeled ribo-CTP (5-iodo-CTP) which was used to prepare cytomegalovirus-specific complementary RNA. The method should be of value in the preparation of viral probes and for use in autoradiography of viral nucleic acids.", "contents": "Iodination of herpesvirus nucleic acids. A simple method is described for the iodination of herpes simplex virus (HSV) DNA. The procedure involved synthesis of 125-I-labeled 5-iodo-dCTP which was subsequently used as a precursor for the in vitro repair synthesis of HSV DNA. Synthesis of 5-iodo-dCTP and purification from oxidation and reduction reagents, buffer salts, unreacted dCTP and Na125-I was accomplished in a single chromatographic step. It was possible to prepare 125-I-labeled HSV DNA in vitro with specific activities exceeding 10-8 counts/min/mu-g. The DNA prepared by this method reassociated with DNA extracted from HSV-infected HEp-2 cells but not with HEp-2 cell DNA. Iodinated HSV DNA was susceptible to S-1-endonuclease digestion once denatured but was resistant to digestion in the native form. This method was used to synthesize 125-I-labeled ribo-CTP (5-iodo-CTP) which was used to prepare cytomegalovirus-specific complementary RNA. The method should be of value in the preparation of viral probes and for use in autoradiography of viral nucleic acids."} {"id": "PMID:166202", "title": "Anatomy of herpes simplex virus DNA. III. Characterization of defective DNA molecules and biological properties of virus populations containing them.", "content": "We have characterized the virus progeny and its DNA from plaque-purified and undiluted passages of herpes simplex virus 1 in HEp-2 cells. Secifically, (i) infectious virus yields declined progressively in passages 1 through 10 and gradually increased at passages 11 through 14. The yields correlated with PFU/particle ratios. (ii) In cells infected with virus from passages 6 through 10, there was an overproduction of an early viral polypeptide (no. 4) and a delay in the synthesis of late viral proteins. In addition, the virus in these passages interfered with the replication of a nondefective marker virus. Cells infected with passage 14 virus produced normal amounts of polypeptide 4 and, moreover, this virus showed minimal interfering capacity. (iii) In addition to DNA of density 1.726 g/cm-3, which was the sole component present in viral progeny of passage 0, passages 6 through 14 contained one additional species (p 1.732) and in some instances (passages 6 and 10) also DNA of an intermediate buoyant density. The ratio of p 1.732 to p 1.726 DNA increased to a maximum of 4 in passages 6 through 9 and gradually decreased to 1 in passages 10 through 14. (iv) p 1.732 DNA cannot be differentiated from p 1.726 DNA with respect to size; however, it has no Hin III restriction enzyme cleavage sites and yields only predominantly two kinds of fragments with molecular weights of 5.1 x 10-6 and 5.4 x 10-6 upon digestion with EcoRI enzyme. (v) Partial denaturation profiles of purified p 1.732 DNA from passage 14 revealed the presence of two types of tandemly repeated units corresponding roughly in size to the EcoRI fragments and situated in different molecules. (vi) In addition to the two kinds of p 1.732 molecules consisting of tandem repaeat units of different sizes, other evidence for the diversity of defective DNA molecules emerged from comparisons of specific infectivity and interfering capacity of the progeny from various passages. The data suggest that some of the particles with DNA of normal buoyant density (1.726) must also be defective since the capacity to interfere and to produce an excess of polypeptide 4 did not appear to be proportional to the amount of high-buoyant-density defective DNA. The data suggest that defective interfering particles are replaced by defective particles with diminished capacity to interfere and that more than one species of defective DNA molecules evolves on serial preparation of HSV.", "contents": "Anatomy of herpes simplex virus DNA. III. Characterization of defective DNA molecules and biological properties of virus populations containing them. We have characterized the virus progeny and its DNA from plaque-purified and undiluted passages of herpes simplex virus 1 in HEp-2 cells. Secifically, (i) infectious virus yields declined progressively in passages 1 through 10 and gradually increased at passages 11 through 14. The yields correlated with PFU/particle ratios. (ii) In cells infected with virus from passages 6 through 10, there was an overproduction of an early viral polypeptide (no. 4) and a delay in the synthesis of late viral proteins. In addition, the virus in these passages interfered with the replication of a nondefective marker virus. Cells infected with passage 14 virus produced normal amounts of polypeptide 4 and, moreover, this virus showed minimal interfering capacity. (iii) In addition to DNA of density 1.726 g/cm-3, which was the sole component present in viral progeny of passage 0, passages 6 through 14 contained one additional species (p 1.732) and in some instances (passages 6 and 10) also DNA of an intermediate buoyant density. The ratio of p 1.732 to p 1.726 DNA increased to a maximum of 4 in passages 6 through 9 and gradually decreased to 1 in passages 10 through 14. (iv) p 1.732 DNA cannot be differentiated from p 1.726 DNA with respect to size; however, it has no Hin III restriction enzyme cleavage sites and yields only predominantly two kinds of fragments with molecular weights of 5.1 x 10-6 and 5.4 x 10-6 upon digestion with EcoRI enzyme. (v) Partial denaturation profiles of purified p 1.732 DNA from passage 14 revealed the presence of two types of tandemly repeated units corresponding roughly in size to the EcoRI fragments and situated in different molecules. (vi) In addition to the two kinds of p 1.732 molecules consisting of tandem repaeat units of different sizes, other evidence for the diversity of defective DNA molecules emerged from comparisons of specific infectivity and interfering capacity of the progeny from various passages. The data suggest that some of the particles with DNA of normal buoyant density (1.726) must also be defective since the capacity to interfere and to produce an excess of polypeptide 4 did not appear to be proportional to the amount of high-buoyant-density defective DNA. The data suggest that defective interfering particles are replaced by defective particles with diminished capacity to interfere and that more than one species of defective DNA molecules evolves on serial preparation of HSV."} {"id": "PMID:166203", "title": "Regulation of tumor antigen synthesis by simain virus 40 gene A.", "content": "Simian virus 40 gene A has previously been shown to promote the replication of viral DNA and the transcription of late viral RNA in productive infection and to maintain the growth characteristics of some transformed cells. The present study examines the effect of the A function on proteins synthesized during productive and transforming infections. Under restrictive conditions, temperature-sensitive A mutants induce the overproduction of a 100,000-dalton protein both in productively infected monkey cells and in transformed rabbit cells. Immunoprecipitation of the induced protein with antisera, prepared against simian virus 40-induced tumors in hamsters, was used to identify the induced protein as tumor antigen. The same protein can be precipitated from extracts of cells infected by wild-type virus but not from uninfected cells. Furthermore, the mutant-induced protein is more rapidly degraded in vivo and is less tightly bound to intranuclear components than the protein induced by wild-type virus. The presence of the same virus-induced protein in infected cells from different species and the altered behavior of that protein in mutant infection strongly suggest that the protein is virus coded. Because the protein is large enough to account for the entire coding capacity in the early region of the simian virus 40 genome, the 100,000-dalton protein may well be the primary product of the only early gene identified by complementation studies, the A gene. If the 100,000-dalton protein that is overproduced in mutant infection is the A protein and the only early protein, then functional wild-type A protein must regulate its own synthesis in both productive and transforming infections.", "contents": "Regulation of tumor antigen synthesis by simain virus 40 gene A. Simian virus 40 gene A has previously been shown to promote the replication of viral DNA and the transcription of late viral RNA in productive infection and to maintain the growth characteristics of some transformed cells. The present study examines the effect of the A function on proteins synthesized during productive and transforming infections. Under restrictive conditions, temperature-sensitive A mutants induce the overproduction of a 100,000-dalton protein both in productively infected monkey cells and in transformed rabbit cells. Immunoprecipitation of the induced protein with antisera, prepared against simian virus 40-induced tumors in hamsters, was used to identify the induced protein as tumor antigen. The same protein can be precipitated from extracts of cells infected by wild-type virus but not from uninfected cells. Furthermore, the mutant-induced protein is more rapidly degraded in vivo and is less tightly bound to intranuclear components than the protein induced by wild-type virus. The presence of the same virus-induced protein in infected cells from different species and the altered behavior of that protein in mutant infection strongly suggest that the protein is virus coded. Because the protein is large enough to account for the entire coding capacity in the early region of the simian virus 40 genome, the 100,000-dalton protein may well be the primary product of the only early gene identified by complementation studies, the A gene. If the 100,000-dalton protein that is overproduced in mutant infection is the A protein and the only early protein, then functional wild-type A protein must regulate its own synthesis in both productive and transforming infections."} {"id": "PMID:166204", "title": "In vitro transformation of rat and mouse cells by DNA from simian virus 40.", "content": "Primary rat kidney cells and mouse 3T3 cells can be transformed by DNA of simian virus 40 when use is made of the calcium technique (Graham and van der Eb, 1973). The transformation assay in primary rat cells is reproducible, but the dose response is not linear.", "contents": "In vitro transformation of rat and mouse cells by DNA from simian virus 40. Primary rat kidney cells and mouse 3T3 cells can be transformed by DNA of simian virus 40 when use is made of the calcium technique (Graham and van der Eb, 1973). The transformation assay in primary rat cells is reproducible, but the dose response is not linear."} {"id": "PMID:166205", "title": "UV-induced reversion of a temperature-sensitive late mutant of simian virus 40 to a wild-type phenotype.", "content": "Irradiation of a simian virus 40 temperature-sensitive late mutant before infection of CV1 cells produces viruses that are phenotypically wild-type revertants. This probably occurs through suppression rather than true reversion because the revertants are produced at relatively high frequency and still have some properties of the original temperature-sensitive virus.", "contents": "UV-induced reversion of a temperature-sensitive late mutant of simian virus 40 to a wild-type phenotype. Irradiation of a simian virus 40 temperature-sensitive late mutant before infection of CV1 cells produces viruses that are phenotypically wild-type revertants. This probably occurs through suppression rather than true reversion because the revertants are produced at relatively high frequency and still have some properties of the original temperature-sensitive virus."} {"id": "PMID:166206", "title": "Simian virus 40 DNA replication, transcription, and antigen induction during infection with two adenovirus 2-SV40 hybrids that contain the entire SV40 genome.", "content": "The Ad2++hey hybrid virus population produces simian virus 40 (SV40) efficiently during lytic infection, whereas Ad2++ley does not, although both hybrids contain a complete SV40 genome. In this report, we demonstrate the synthesis of nonhydrid SV40 DNA in Ad2++HEY-infected Vero cells, but only early SV40 RNA is transcribed efficiently in Ad2++LEY-infected cells. Ad2++HEY induces SV40 U, T, and V antigens during lytic infection of African green monkey kidney cells, whereas Ad2++LEY induces only SV40 U and T antigens. These variations in the behavior of Ad2++HEY and Ad2++LEY regarding expression of SV40 functions probably reflect differences in the rate of SV40 excision from the hybrid genomes.", "contents": "Simian virus 40 DNA replication, transcription, and antigen induction during infection with two adenovirus 2-SV40 hybrids that contain the entire SV40 genome. The Ad2++hey hybrid virus population produces simian virus 40 (SV40) efficiently during lytic infection, whereas Ad2++ley does not, although both hybrids contain a complete SV40 genome. In this report, we demonstrate the synthesis of nonhydrid SV40 DNA in Ad2++HEY-infected Vero cells, but only early SV40 RNA is transcribed efficiently in Ad2++LEY-infected cells. Ad2++HEY induces SV40 U, T, and V antigens during lytic infection of African green monkey kidney cells, whereas Ad2++LEY induces only SV40 U and T antigens. These variations in the behavior of Ad2++HEY and Ad2++LEY regarding expression of SV40 functions probably reflect differences in the rate of SV40 excision from the hybrid genomes."} {"id": "PMID:166207", "title": "Role of gene 59 of bacteriophage T4 in repair of UV-irradiated and alkylated DNA in vivo.", "content": "Nonsense mutants in gene 59 (amC5, amHL628) were used to study the role of this gene in the repair of UV-damaged and alkylated DNA of bacteriophage T4 in vivo. The higher sensitivity to UV irradiation and alkylation of gene 59 mutants after exposure to these agents was established by a comparison of the survival fractions with wild type. Zonal centrifugal analysis of both parental and nascent mutant intracellular DNA molecules after UV irradiation showed that immediately after exposure the size of single-stranded DNA fragments was the same as the wild-type intracellular DNA. However, the capability of rejoining fragmented intracellular DNA was greatly reduced in the mutant. In contrast, the wild-type-infected cells under the same condition resumed DNA replication and repaired its DNA to normal size. Methyl methanesulfonate induced more randomly fragmented intracellular DNA, when compared to UV irradiation. The rate of rejoining under these conditions as judged from their sedimentation profiles was also greatly reduced in mutant-infected cells. Further evidence is presented that UV repair is not a simple consequence of arrested DNA replication, which is a phenotype of the mutant when infected in a nonpermissive host, Escherichia coli B (su minus), but rather that the DNA repair function of gene 59 is independent of the replication function. These and other data presented indicate that a product(s) of gene 59 is essential for both repair of UV lesions and repair of alkylation damage of DNA in vivo. It is suggested that gene 59 may have two functions during viral development: DNA replication and replication repair of DNA molecules.", "contents": "Role of gene 59 of bacteriophage T4 in repair of UV-irradiated and alkylated DNA in vivo. Nonsense mutants in gene 59 (amC5, amHL628) were used to study the role of this gene in the repair of UV-damaged and alkylated DNA of bacteriophage T4 in vivo. The higher sensitivity to UV irradiation and alkylation of gene 59 mutants after exposure to these agents was established by a comparison of the survival fractions with wild type. Zonal centrifugal analysis of both parental and nascent mutant intracellular DNA molecules after UV irradiation showed that immediately after exposure the size of single-stranded DNA fragments was the same as the wild-type intracellular DNA. However, the capability of rejoining fragmented intracellular DNA was greatly reduced in the mutant. In contrast, the wild-type-infected cells under the same condition resumed DNA replication and repaired its DNA to normal size. Methyl methanesulfonate induced more randomly fragmented intracellular DNA, when compared to UV irradiation. The rate of rejoining under these conditions as judged from their sedimentation profiles was also greatly reduced in mutant-infected cells. Further evidence is presented that UV repair is not a simple consequence of arrested DNA replication, which is a phenotype of the mutant when infected in a nonpermissive host, Escherichia coli B (su minus), but rather that the DNA repair function of gene 59 is independent of the replication function. These and other data presented indicate that a product(s) of gene 59 is essential for both repair of UV lesions and repair of alkylation damage of DNA in vivo. It is suggested that gene 59 may have two functions during viral development: DNA replication and replication repair of DNA molecules."} {"id": "PMID:166208", "title": "Chromatographic separation and antigenic analysis of proteins of the oncornaviruses. V. Identification of a new murine viral protein, p15(E).", "content": "Profiling of murine leukemia virus (MuLV) proteins by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) has revealed a low-molecular-weight protein which does not appear in the corresponding region of viral protein profiles obtained by gel filtration in 6 M guanidine hydrochloride. This protein species, termed p15(E), is easily demonstrable in MuLV isolates for which the viral p15 and p12 proteins have almost identical electrophoretic mobilities; this leaves a protein slightly larger than these two in the PAGE system unaccounted for in the gel filtration system. However, antiserum against the void volume fraction of the gel filtration eluate precipitated the p15(E) component from solubilized, radiolabeled virions, as shown by SDS-PAGE analysis of such immunoprecipitates. Comparative radioprecipitation analyses of this type revealed that for various MuLV isolates p15(E) was distinguishable from p15 in terms of serological reactivities, relative mobilities in gel electrophoresis, and relative efficiencies of labeling with individual amino acids. Thus it appears that, as is the case for avian oncornaviruses, MuLVs contain seven major structural proteins.", "contents": "Chromatographic separation and antigenic analysis of proteins of the oncornaviruses. V. Identification of a new murine viral protein, p15(E). Profiling of murine leukemia virus (MuLV) proteins by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) has revealed a low-molecular-weight protein which does not appear in the corresponding region of viral protein profiles obtained by gel filtration in 6 M guanidine hydrochloride. This protein species, termed p15(E), is easily demonstrable in MuLV isolates for which the viral p15 and p12 proteins have almost identical electrophoretic mobilities; this leaves a protein slightly larger than these two in the PAGE system unaccounted for in the gel filtration system. However, antiserum against the void volume fraction of the gel filtration eluate precipitated the p15(E) component from solubilized, radiolabeled virions, as shown by SDS-PAGE analysis of such immunoprecipitates. Comparative radioprecipitation analyses of this type revealed that for various MuLV isolates p15(E) was distinguishable from p15 in terms of serological reactivities, relative mobilities in gel electrophoresis, and relative efficiencies of labeling with individual amino acids. Thus it appears that, as is the case for avian oncornaviruses, MuLVs contain seven major structural proteins."} {"id": "PMID:166209", "title": "Fate of polyoma form IDNA during replication.", "content": "The fate of polyoma form IDNA generated during replication was investigated in resting BALB-3T3 cells. The experiments showed that there was extensive re-entry of such molecules into replication. This process took place over a period of several hours and appeared to be random. Progeny form I molecules must, therefore, spend some time in a nonreplicating pool before reinitiating replication. We propose that two factors affect the fate of progeny form IDNA. (i) The rate of reinitiation of progeny molecules is determined by the capacity of the initiation machinery. (ii) The extent of re-entry is determined by the availability of maturation proteins which divert form I from replication.", "contents": "Fate of polyoma form IDNA during replication. The fate of polyoma form IDNA generated during replication was investigated in resting BALB-3T3 cells. The experiments showed that there was extensive re-entry of such molecules into replication. This process took place over a period of several hours and appeared to be random. Progeny form I molecules must, therefore, spend some time in a nonreplicating pool before reinitiating replication. We propose that two factors affect the fate of progeny form IDNA. (i) The rate of reinitiation of progeny molecules is determined by the capacity of the initiation machinery. (ii) The extent of re-entry is determined by the availability of maturation proteins which divert form I from replication."} {"id": "PMID:166210", "title": "Restitution of infectivity to spikeless vesicular stomatitis virus by solubilized viral components.", "content": "Noninfectious spikeless particles have been obtained from vesicular stomatitis virus (VSV, Indiana serotype) by bromelain or Pronase treatment. They lack the viral glycoprotein (G) but contain all the other viral components (RNA, lipid, and other structural proteins). Triton-solubilized VSV-Indiana glycoprotein preparations, containing the viral G protein as well as lipids (including phospholipids), have been extracted from whole virus preparations, freed from the majority of the detergent, and used to restore infectivity to spikeless VSV. The infectivity of such particles has been found to be enhanced by poly-L-ornithine but inhibited by Trition or homologous antiserum pretreatment. Heat-denatured glycoprotein preparations were not effective in restoring the infectivity to spikeless VSV. Heterologous glycoprotein preparations from the serologically distinct VSV-New Jersey serotype were equally capable of making infectious entities with VSV-Indiana spikeless particles, and the infectivity of these structures was inhibited by VSV-New Jersey antiserum but not by VSV-Indiana antiserum. Purified, detergent-free glycoprotein selectively solubilized from VSV-Indiana by the dialyzable detergent, octylglucoside, also restored infectivity of spikeless virions of VSV-Indiana and VSV-New Jersey.", "contents": "Restitution of infectivity to spikeless vesicular stomatitis virus by solubilized viral components. Noninfectious spikeless particles have been obtained from vesicular stomatitis virus (VSV, Indiana serotype) by bromelain or Pronase treatment. They lack the viral glycoprotein (G) but contain all the other viral components (RNA, lipid, and other structural proteins). Triton-solubilized VSV-Indiana glycoprotein preparations, containing the viral G protein as well as lipids (including phospholipids), have been extracted from whole virus preparations, freed from the majority of the detergent, and used to restore infectivity to spikeless VSV. The infectivity of such particles has been found to be enhanced by poly-L-ornithine but inhibited by Trition or homologous antiserum pretreatment. Heat-denatured glycoprotein preparations were not effective in restoring the infectivity to spikeless VSV. Heterologous glycoprotein preparations from the serologically distinct VSV-New Jersey serotype were equally capable of making infectious entities with VSV-Indiana spikeless particles, and the infectivity of these structures was inhibited by VSV-New Jersey antiserum but not by VSV-Indiana antiserum. Purified, detergent-free glycoprotein selectively solubilized from VSV-Indiana by the dialyzable detergent, octylglucoside, also restored infectivity of spikeless virions of VSV-Indiana and VSV-New Jersey."} {"id": "PMID:166211", "title": "Brain scans, dexamethasone therapy, and brain tumors.", "content": "Eight men with primary or metastatic brain tumors were examined with brain scans before and after the administration of dexamethasone. All patients demonstrated some improvement in their clinical neurologic status during therapy, and two patients had a dramatic response. Seven of the eight patients examined showed a decrease in the apparent size of the original lesion on recent brain scan while receiving dexamethasone. Comparison of immediate scans obtained 15 to 20 minutes following the administration of sodium pertechnetate Tc 99m with those obtained two or three hours later suggests that the change in apparent size of the original lesion results from decrease in peritumor edema.", "contents": "Brain scans, dexamethasone therapy, and brain tumors. Eight men with primary or metastatic brain tumors were examined with brain scans before and after the administration of dexamethasone. All patients demonstrated some improvement in their clinical neurologic status during therapy, and two patients had a dramatic response. Seven of the eight patients examined showed a decrease in the apparent size of the original lesion on recent brain scan while receiving dexamethasone. Comparison of immediate scans obtained 15 to 20 minutes following the administration of sodium pertechnetate Tc 99m with those obtained two or three hours later suggests that the change in apparent size of the original lesion results from decrease in peritumor edema."} {"id": "PMID:166231", "title": "Control of aldosterone responsiveness in terminal renal failure.", "content": "Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control.", "contents": "Control of aldosterone responsiveness in terminal renal failure. Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control."} {"id": "PMID:166251", "title": "Spontaneous diabetes mellitus in Macaca cyclopis and Mandrillus leucophaeus: case reports.", "content": "Spontaneous diabetes mellitus was reported in a Mandrillus leucophaeus (drill baboon) and a Mpacaca cyclopis (Formosan rock macaque). Each had hyperglycemia, impaired clearance of glucose during tolerance test, and reduced concentrations of immunoreactive insulin; the M cyclopis also had increased triglyceride and prebetalipoprotein concentrations. Both monkeys had extensive amyloid infiltration into the islets of Langerhans and loss of beta cells. Beta cell obliteration can account for the appearance of the diabetic syndrome in these and other nonhuman primate species.", "contents": "Spontaneous diabetes mellitus in Macaca cyclopis and Mandrillus leucophaeus: case reports. Spontaneous diabetes mellitus was reported in a Mandrillus leucophaeus (drill baboon) and a Mpacaca cyclopis (Formosan rock macaque). Each had hyperglycemia, impaired clearance of glucose during tolerance test, and reduced concentrations of immunoreactive insulin; the M cyclopis also had increased triglyceride and prebetalipoprotein concentrations. Both monkeys had extensive amyloid infiltration into the islets of Langerhans and loss of beta cells. Beta cell obliteration can account for the appearance of the diabetic syndrome in these and other nonhuman primate species."} {"id": "PMID:166259", "title": "Control of arrhythmias following ligation of the circumflex artery.", "content": "In experimental work, three groups of 10 dogs each were subjected to ligation of the circumflex coronary artery. One group was given prophylactic medication with procainamide and another group was allowed a 2 hour interval between thoracotomy and ligation. The effects of these measures on the incidence of ventricular arrhythmias during the 30 minutes immediately after coronary artery occlusion were then compared. The two groups of animals on which these preventive measures were tested both showed a significant reduction in incidence of arrhythmias as compared to the control group. The therapeutic use of procainamide was also assessed by administering the drug intravenously to all animals developing postligation arrhythmias in the two groups which were not prophylactically medicated. In 46 per cent of these cases, the arrhythmias were suppressed and threatened ventricular fibrillation was obviated.", "contents": "Control of arrhythmias following ligation of the circumflex artery. In experimental work, three groups of 10 dogs each were subjected to ligation of the circumflex coronary artery. One group was given prophylactic medication with procainamide and another group was allowed a 2 hour interval between thoracotomy and ligation. The effects of these measures on the incidence of ventricular arrhythmias during the 30 minutes immediately after coronary artery occlusion were then compared. The two groups of animals on which these preventive measures were tested both showed a significant reduction in incidence of arrhythmias as compared to the control group. The therapeutic use of procainamide was also assessed by administering the drug intravenously to all animals developing postligation arrhythmias in the two groups which were not prophylactically medicated. In 46 per cent of these cases, the arrhythmias were suppressed and threatened ventricular fibrillation was obviated."} {"id": "PMID:166265", "title": "Effect of acute dietary alteration upon intestinal lipid synthesis.", "content": "The specific activities of three enzymes engaged in complex lipid synthesis, diglyceride acyltransferase, cholinephosphotransferase, and lysolecithin acyltransferase were studied in intestinal mucosa of hamsters fed either saline, hydrolyzed casein, or corn oil for 9 1/2 hr. In the most proximal intestine, saline feeding was associated with a reduced specific activity in villous tips with all three enzymes studied when compared with the two caloric supplemented groups. In the most distal intestine, oil feeding increased the activity of lysolecithin acyltransferase and choline phosphotransferase twofold as compared to casein fed hamsters; diglyceride acyltransferase was increased one- and one-half-fold. The response of lysolecithin acyltransferase and diglyceride acyltransferase to fat feeding was incomplete when compared to hamsters fed a fat supplemented diet for 7 days, suggesting that their pattern of response to dietary substrate was similar to the disaccharidases. By contrast, the response of cholinephosphotransferase to fat feeding was complete at 24 hr, suggesting that it responds in a manner similar to the glycolytic enzymes.", "contents": "Effect of acute dietary alteration upon intestinal lipid synthesis. The specific activities of three enzymes engaged in complex lipid synthesis, diglyceride acyltransferase, cholinephosphotransferase, and lysolecithin acyltransferase were studied in intestinal mucosa of hamsters fed either saline, hydrolyzed casein, or corn oil for 9 1/2 hr. In the most proximal intestine, saline feeding was associated with a reduced specific activity in villous tips with all three enzymes studied when compared with the two caloric supplemented groups. In the most distal intestine, oil feeding increased the activity of lysolecithin acyltransferase and choline phosphotransferase twofold as compared to casein fed hamsters; diglyceride acyltransferase was increased one- and one-half-fold. The response of lysolecithin acyltransferase and diglyceride acyltransferase to fat feeding was incomplete when compared to hamsters fed a fat supplemented diet for 7 days, suggesting that their pattern of response to dietary substrate was similar to the disaccharidases. By contrast, the response of cholinephosphotransferase to fat feeding was complete at 24 hr, suggesting that it responds in a manner similar to the glycolytic enzymes."} {"id": "PMID:166269", "title": "Broad-beta disease versus endogenous hypertriglyceridemia: levels and lipid composition of chylomicrons and very low density lipoproteins during fat-free feeding and alimentary lipemia.", "content": "To assess the roles of endogenous and exogenous lipid in the production of the abnormal lipoprotein patterns characteristic of broad-beta desease (with a type IVIII lipoprotein pattern) and endogenous hypertriglyceridemia (with a type IV pattern), oral fat loads (50 g/M-2) were administered to six subjects with broad-beta disease and to eight with endogenous hypertriglyceridemia following at leat 72 hr of 0% fat, 85% carbohydrate isocaloric formula feeding. Total plasma and Sf greater than 400, 100-400, 60-100, 30-60, and 20-30 lipoprotein cholesterol, triglyceride, and phospholipid levels were measured at 0 hr, 6 hr (at or before the peak of alimentary lipemia), and 24 hr following the fat load. Following fat-free feeding the levels and composition of the endogenous Sf greater than 400 lipoproteins were similar in both disorders; whereas total Sf20-400, and most notably, Sf 30-60 and 20-30 levels were increased and enriched in cholesterol in the subjects with broad-beta disease.", "contents": "Broad-beta disease versus endogenous hypertriglyceridemia: levels and lipid composition of chylomicrons and very low density lipoproteins during fat-free feeding and alimentary lipemia. To assess the roles of endogenous and exogenous lipid in the production of the abnormal lipoprotein patterns characteristic of broad-beta desease (with a type IVIII lipoprotein pattern) and endogenous hypertriglyceridemia (with a type IV pattern), oral fat loads (50 g/M-2) were administered to six subjects with broad-beta disease and to eight with endogenous hypertriglyceridemia following at leat 72 hr of 0% fat, 85% carbohydrate isocaloric formula feeding. Total plasma and Sf greater than 400, 100-400, 60-100, 30-60, and 20-30 lipoprotein cholesterol, triglyceride, and phospholipid levels were measured at 0 hr, 6 hr (at or before the peak of alimentary lipemia), and 24 hr following the fat load. Following fat-free feeding the levels and composition of the endogenous Sf greater than 400 lipoproteins were similar in both disorders; whereas total Sf20-400, and most notably, Sf 30-60 and 20-30 levels were increased and enriched in cholesterol in the subjects with broad-beta disease."} {"id": "PMID:166270", "title": "Stimulation of human purine synthesis de novo by fructose infusion.", "content": "In order to clarify the mechanism of hyperuricemia and hyperuricosuria resulting from rapid infusion of fructose in man, the effects of an intravenous infusion of 125-200 g of fructose given over 3-4 hr on the rate of purine synthesis de novo was measured in one individual with osteoarthritis and four patients with gout. The incorporation of 1-minus 14C glycine into urinary uric acid was measured, and the pool size and turnover of urate were assessed by renal excretion of simultaneously administered 15-N urate. Fructose caused an expansion of body urate pool in all subjects, while urate turnover was increased in four. The rate of incorporation of 14-C glycine into urinary uric acid corrected for extrarenal disposal was increased in all cases (21%-430%). In two patients, rates of incorporation of 14-C glycine into urinary creatinine were increased by 10% and 11%, while rates of incorporation into uric acid were increased 84% and 159%, respectively, as a result of fructose infusion. Specific enhancement of the rate of purine synthesis de novo was suggested by these findings. The rate of infusion appeared more important than total dose in determining the magnitude of this effect. Whether the increased rate of purine synthesis was a result of direct stimulation by a fructose metabolite or was secondary to fructose-induced purine nucleotide depletion is uncertain, since the kinetics of glycine incorporation were consistent with either mechanism. Erythrocyte PP-ribose-P concentrations, however, were diminished during infusion rather than increased as might be expected if fructose infusion stimulated purine synthesis by increasing availability of this regulatory substrate.", "contents": "Stimulation of human purine synthesis de novo by fructose infusion. In order to clarify the mechanism of hyperuricemia and hyperuricosuria resulting from rapid infusion of fructose in man, the effects of an intravenous infusion of 125-200 g of fructose given over 3-4 hr on the rate of purine synthesis de novo was measured in one individual with osteoarthritis and four patients with gout. The incorporation of 1-minus 14C glycine into urinary uric acid was measured, and the pool size and turnover of urate were assessed by renal excretion of simultaneously administered 15-N urate. Fructose caused an expansion of body urate pool in all subjects, while urate turnover was increased in four. The rate of incorporation of 14-C glycine into urinary uric acid corrected for extrarenal disposal was increased in all cases (21%-430%). In two patients, rates of incorporation of 14-C glycine into urinary creatinine were increased by 10% and 11%, while rates of incorporation into uric acid were increased 84% and 159%, respectively, as a result of fructose infusion. Specific enhancement of the rate of purine synthesis de novo was suggested by these findings. The rate of infusion appeared more important than total dose in determining the magnitude of this effect. Whether the increased rate of purine synthesis was a result of direct stimulation by a fructose metabolite or was secondary to fructose-induced purine nucleotide depletion is uncertain, since the kinetics of glycine incorporation were consistent with either mechanism. Erythrocyte PP-ribose-P concentrations, however, were diminished during infusion rather than increased as might be expected if fructose infusion stimulated purine synthesis by increasing availability of this regulatory substrate."} {"id": "PMID:166271", "title": "Pathogenesis and management of hypoparathyroidism and other hypocalcemic disorders.", "content": "Hypocalcemia frequently presents as an acute medical emergency or a chronic disorder which is difficult to control. Occasionally, it is found in routine blood screening tests when it is not anticipated. Recent developments in basic endocrine science have contributed greatly to our understanding and treatment of hypocalcemic disorders. The maintanance of a normal serum calcium concentration depends on the balanced actions of parathyroid hormone (PTH), vitamin D, and, to a lesser extent, calcitonin, Recent work on PTH secretion has defined the factors controlling its secretion in normal and abnormal states. In primary hypoparathyroidism, hormone secretion is decreased or absent, while in most other forms of hypocalcemia, secretion is stimulated secondarily by the hypocalcemia. However, acute or chronci disorders associated with hypomagnesemia may also decrease effective PTH secretion. Patients with the rare disorder, pseudohypoparathyroidism, have defects of hormone action and usually have elevated levels of PTH prior to therapy. Several forms of pseudohypoparathyroidism have been recognized, each representing a defect as a different site of PTH action. Calcitonin excess, as noted in medullary carcinoma of the thyroid, could theorectically cause hypocalcemia, but rarely does so. Vitamin D undergoes a series of two carefully controlled hydroxylation reactions leading to the final active metabolite, 1,25-hihyroxycholecalciferol. Chronic ingestion of certain drugs can lead to osteomalacia and hypocalcemia by potentiating the metabolism of vitamin D to inactive compounds. At least one form of rickets has been shown to result from a specific enzyme defect in the vitamin D pathway. Severe renal damage limits the conversion of vitamin D to its active form and contributes to vitamin D resistance. Current progress in the area depends on the development of procedures for the measurement of the metabolites in plasma and assessing the role of the vitamin (hormone) in normal and abnormal physiology. Although the therapy of acute hypocalcemia is usually readily accomplished, chronic hypocalcemia remains a very difficult therapeutic problem. Vitamin D, the hallmark of therapy, is a long-acting drug with a narrow therapeutic range. The complications of the disease and therapy are sometimes irreversible. The unraveling of vitamin D metabolism has led to the development of new therapeutic agents which might provide better relief of chronic hypocalcemic states. This review related new information about calcium homeostasis to the clinical situation encountered in the patient with hypocalcemia.", "contents": "Pathogenesis and management of hypoparathyroidism and other hypocalcemic disorders. Hypocalcemia frequently presents as an acute medical emergency or a chronic disorder which is difficult to control. Occasionally, it is found in routine blood screening tests when it is not anticipated. Recent developments in basic endocrine science have contributed greatly to our understanding and treatment of hypocalcemic disorders. The maintanance of a normal serum calcium concentration depends on the balanced actions of parathyroid hormone (PTH), vitamin D, and, to a lesser extent, calcitonin, Recent work on PTH secretion has defined the factors controlling its secretion in normal and abnormal states. In primary hypoparathyroidism, hormone secretion is decreased or absent, while in most other forms of hypocalcemia, secretion is stimulated secondarily by the hypocalcemia. However, acute or chronci disorders associated with hypomagnesemia may also decrease effective PTH secretion. Patients with the rare disorder, pseudohypoparathyroidism, have defects of hormone action and usually have elevated levels of PTH prior to therapy. Several forms of pseudohypoparathyroidism have been recognized, each representing a defect as a different site of PTH action. Calcitonin excess, as noted in medullary carcinoma of the thyroid, could theorectically cause hypocalcemia, but rarely does so. Vitamin D undergoes a series of two carefully controlled hydroxylation reactions leading to the final active metabolite, 1,25-hihyroxycholecalciferol. Chronic ingestion of certain drugs can lead to osteomalacia and hypocalcemia by potentiating the metabolism of vitamin D to inactive compounds. At least one form of rickets has been shown to result from a specific enzyme defect in the vitamin D pathway. Severe renal damage limits the conversion of vitamin D to its active form and contributes to vitamin D resistance. Current progress in the area depends on the development of procedures for the measurement of the metabolites in plasma and assessing the role of the vitamin (hormone) in normal and abnormal physiology. Although the therapy of acute hypocalcemia is usually readily accomplished, chronic hypocalcemia remains a very difficult therapeutic problem. Vitamin D, the hallmark of therapy, is a long-acting drug with a narrow therapeutic range. The complications of the disease and therapy are sometimes irreversible. The unraveling of vitamin D metabolism has led to the development of new therapeutic agents which might provide better relief of chronic hypocalcemic states. This review related new information about calcium homeostasis to the clinical situation encountered in the patient with hypocalcemia."} {"id": "PMID:166291", "title": "[Studies to the in-vitro-effectiveness of Spectacillin (author's transl)].", "content": "In this study the sensibility of important disease germs of a clinical and an ambulatory test material has been investigated to the substances \"Epicillin\" and \"Ampicillin\". Thereby could be found that 67% (43%) of the E. coli and 55% (36%) of the proteus type, as well as 96% (96%) of the enterococcus type of the ambulatory (clinical) test material were sensitive to Epicillin and Ampicillin. Staphylococcus not producing penicillinase, were well-sensitive, while staphylococcus producing penicillinase, contrarily showed to be insensitive. Salmonellae proved to be well-sensitive up to 97%, and the rest left was limited sensitive. The minimal inhibitory concentration (MIC) resulted in favourable findings for enterococcus, staphylococcus aureus and salmonellae; at a corresponding sensibility the same is valid for E. coli and the proteus. The investigations carried out in-vitro, reveal an equal effectiveness of Epicillin and Ampicillin.", "contents": "[Studies to the in-vitro-effectiveness of Spectacillin (author's transl)]. In this study the sensibility of important disease germs of a clinical and an ambulatory test material has been investigated to the substances \"Epicillin\" and \"Ampicillin\". Thereby could be found that 67% (43%) of the E. coli and 55% (36%) of the proteus type, as well as 96% (96%) of the enterococcus type of the ambulatory (clinical) test material were sensitive to Epicillin and Ampicillin. Staphylococcus not producing penicillinase, were well-sensitive, while staphylococcus producing penicillinase, contrarily showed to be insensitive. Salmonellae proved to be well-sensitive up to 97%, and the rest left was limited sensitive. The minimal inhibitory concentration (MIC) resulted in favourable findings for enterococcus, staphylococcus aureus and salmonellae; at a corresponding sensibility the same is valid for E. coli and the proteus. The investigations carried out in-vitro, reveal an equal effectiveness of Epicillin and Ampicillin."} {"id": "PMID:166292", "title": "[Experimental investigations concerning spectrum, serum concentration, and excretion of Spectacillin (author's transl)].", "content": "By means of the diffusion test, the range of action of the ampicillin successive preparation spectacillin was determined using 12 000 pathological germs freshly isolated from in-patients. The result was a range of action similar to that of ampicillin. A comparison, however, is only possible in case the test platelets (without over-dosage) are each charged with exactly, e.g., 25 gamma. The analyses of serum concentrations have shown that spectacillin is satisfactorily absorbed after oral as well as after parenteral application. Thus, the calculation of the accumulated area of infinity beneath the serum concentration curve had the following results: After single intravenous injection of 1 g spectacillin (n equals 12) 51.46 gamma/ml - h; after single intravenous injection of 2 g spectacillin 86.20 gamma/ml - h; after intramuscular injection (twice) - interval of 12 hours - 29.94 gamma/ml - h after 12 hours; same values as before, but after 24 hours, 29.37 gamma/ml - h. After a single oral application of one capsule of spectacillin (capsule equals 500 mg), the value of the accumulated area was 8.46 gamma/ml - h. In analogy of the good absorption, excretion in urine/24 hrs (after application of 1 g spectacillin intravenously) was 61.74 p.c., after 2 g i.v. 54.30 p.c., and after applying twice 1 g spectacillin intramuscularly 61.40 p.c.; after oral application of 500 mg, the percentage was 28.42. Tolerance of spectacillin was good after oral as well as after parenteral application. No side effects were observed.", "contents": "[Experimental investigations concerning spectrum, serum concentration, and excretion of Spectacillin (author's transl)]. By means of the diffusion test, the range of action of the ampicillin successive preparation spectacillin was determined using 12 000 pathological germs freshly isolated from in-patients. The result was a range of action similar to that of ampicillin. A comparison, however, is only possible in case the test platelets (without over-dosage) are each charged with exactly, e.g., 25 gamma. The analyses of serum concentrations have shown that spectacillin is satisfactorily absorbed after oral as well as after parenteral application. Thus, the calculation of the accumulated area of infinity beneath the serum concentration curve had the following results: After single intravenous injection of 1 g spectacillin (n equals 12) 51.46 gamma/ml - h; after single intravenous injection of 2 g spectacillin 86.20 gamma/ml - h; after intramuscular injection (twice) - interval of 12 hours - 29.94 gamma/ml - h after 12 hours; same values as before, but after 24 hours, 29.37 gamma/ml - h. After a single oral application of one capsule of spectacillin (capsule equals 500 mg), the value of the accumulated area was 8.46 gamma/ml - h. In analogy of the good absorption, excretion in urine/24 hrs (after application of 1 g spectacillin intravenously) was 61.74 p.c., after 2 g i.v. 54.30 p.c., and after applying twice 1 g spectacillin intramuscularly 61.40 p.c.; after oral application of 500 mg, the percentage was 28.42. Tolerance of spectacillin was good after oral as well as after parenteral application. No side effects were observed."} {"id": "PMID:166298", "title": "The regulation of glycerol 3-phosphate oxidase of rate brownadipose tissue mitochondria by long-chain free fatty acids.", "content": "Added free fatty acids inhibit oxidation of glycerol 3-phosphate, succinate and NADH in brown-adipose tissue mitochondria from 10-day-old rats. The most pronounced is the inhibitory effect of glycerol 3-phosphate cytochrome c reductase (GP-cyto. c reductase). Contrary to other reductases, GP-cyto. c reductase activity of freshly isolated mitochondria is already inhibited by the fraction of endogenous free fatty acids. Both added and endogenous free fatty acids inhibition of GP-cyto. c reductase is fully reversible by the removal of free fatty acids by bovine serum albumine treatment. The inhibition of GP-cyto. c reductase is of strictly non-competitive type. The most inhibitory are unsaturated long-chain free fatty acids-oleic and linoleic acid. Results are discussed with regards to the regulatory importance of free fatty acids in brown-adiposetissue during intensive non-shivering thermogenesis.", "contents": "The regulation of glycerol 3-phosphate oxidase of rate brownadipose tissue mitochondria by long-chain free fatty acids. Added free fatty acids inhibit oxidation of glycerol 3-phosphate, succinate and NADH in brown-adipose tissue mitochondria from 10-day-old rats. The most pronounced is the inhibitory effect of glycerol 3-phosphate cytochrome c reductase (GP-cyto. c reductase). Contrary to other reductases, GP-cyto. c reductase activity of freshly isolated mitochondria is already inhibited by the fraction of endogenous free fatty acids. Both added and endogenous free fatty acids inhibition of GP-cyto. c reductase is fully reversible by the removal of free fatty acids by bovine serum albumine treatment. The inhibition of GP-cyto. c reductase is of strictly non-competitive type. The most inhibitory are unsaturated long-chain free fatty acids-oleic and linoleic acid. Results are discussed with regards to the regulatory importance of free fatty acids in brown-adiposetissue during intensive non-shivering thermogenesis."} {"id": "PMID:166299", "title": "[The value of pyrophosphate scintigraphy for the assessment of the activity of spondylarthritis ankylopoietica (author's transl)].", "content": "Seriological and scintigraphic activity was compared in 29 patients with spondylarthritis ankylopoietica (Bechterew's disease). Among our cases, 11 serologically active patients also had positive scans. the details being: cervical vertebral column in 5, thoracic vertebral column in 7 cases and the lumbar vertebral column and iliosacral joint in all 11 patients. In the group of 16 serologically inactive patients, 12 cases could be confirmed radiologically, in the remaining 4 early detection of ankylosing spondylarthritis was possible from the scintigraphic findings in combination with the clinical symptoms. The clinically suspected diagnosis of an incipient Bechterew's disease could not be justified in the remaining 2 patients who had no positive scintigraphic or serological results.", "contents": "[The value of pyrophosphate scintigraphy for the assessment of the activity of spondylarthritis ankylopoietica (author's transl)]. Seriological and scintigraphic activity was compared in 29 patients with spondylarthritis ankylopoietica (Bechterew's disease). Among our cases, 11 serologically active patients also had positive scans. the details being: cervical vertebral column in 5, thoracic vertebral column in 7 cases and the lumbar vertebral column and iliosacral joint in all 11 patients. In the group of 16 serologically inactive patients, 12 cases could be confirmed radiologically, in the remaining 4 early detection of ankylosing spondylarthritis was possible from the scintigraphic findings in combination with the clinical symptoms. The clinically suspected diagnosis of an incipient Bechterew's disease could not be justified in the remaining 2 patients who had no positive scintigraphic or serological results."} {"id": "PMID:166304", "title": "Complementing xeroderma pigmentosum fibroblasts restore biological activity to UV-damaged DNA.", "content": "UV survival curves of adenovirus 2 using fused, complementing xeroderma pigmentosum (XP) fibroblast strains as virus hosts showed a component with an inactivation slope identical to that given by normal cells. This component was not observed when the fibroblasts were not fused or when fusion involved strains in the same complementation group. Extrapolation of this component indicated that at zero dose 3% of the viral plaque-forming units had infected cells capable of normal repair. These results suggest that 3% of the cells were complementing heterokaryons, a value similar to that actually observed by autoradiographic analysis of UV-induced unscheduled DNA synthesis. Thus, heterokaryons formed from XP fibroblasts belonging to different complementation groups are as capable of restoring biological activity to UV-damaged adenovirus 2 as are normal cells.", "contents": "Complementing xeroderma pigmentosum fibroblasts restore biological activity to UV-damaged DNA. UV survival curves of adenovirus 2 using fused, complementing xeroderma pigmentosum (XP) fibroblast strains as virus hosts showed a component with an inactivation slope identical to that given by normal cells. This component was not observed when the fibroblasts were not fused or when fusion involved strains in the same complementation group. Extrapolation of this component indicated that at zero dose 3% of the viral plaque-forming units had infected cells capable of normal repair. These results suggest that 3% of the cells were complementing heterokaryons, a value similar to that actually observed by autoradiographic analysis of UV-induced unscheduled DNA synthesis. Thus, heterokaryons formed from XP fibroblasts belonging to different complementation groups are as capable of restoring biological activity to UV-damaged adenovirus 2 as are normal cells."} {"id": "PMID:166305", "title": "Involvement of separate pathways in the repair of mutational and lethal lesions induced by a monofunctional sulfur mustard.", "content": "The mutagenic and lethal effects of a monofunctional sulfur mustard, 2-chloro-ethylethylsulfide (CEES), have been studied in a number of repair deficient variants of Escherichia coli K12, B/r and B. The results indicate that CEES induces a (pre)mutational lesion which is subject to Uvr+-excision-repair. Extensive CEES-induced mutagenesis can occur in exrA- uvrA- and recA- uvrB- variants suggesting that the majority of the mutations in Uvr-bacteria do not arise from error-prone repair. These findings are similar to results previously reported with a volatile degradation product of captan and with ethyl methanesulfonate (EMS) but differ from those reported with methyl methanesulfonate (MMS). It is hypothesized that CEES alkylates guanine at the O-6 position (R-O-6-G) and that this R-O-6-G which is Uvr+-excisable is directly mutagenic by producing G-C to A-T transitions during replication. Reduced levels of induced mutation frequencies observed in an endonuclease II-deficient variant lead us to postulate that, in constrast to Uvr- bacteria, CEES-induced mutation in wild-type cells arise from error-prone repair of apurinic sites. Analysis of the lethal actions of CEES indicates that the lesion produced is largely unexcisable by the Uvr+ system. Host-cell reactivation of CEES-treated TI bacteriophage shows that the production of the (pre)ethal lesion is dependent on both the initial dose and post-treatment incubation. The efficient repair of the (pre)ethal lesion requires both endonuclease II and polymerase I. Moreover, deficiencies of these two enzymes rendered bacteria more sensitive to the cytotoxic action of CEES. It is postulated that the lethal mechanism of CEES involves: (I) alkylation at the N-3 position of adenine and the N-7 position of guanine; (2) spontaneous depurination of these alkylated bases; and (3) production of apurinic sites which are lethal unless repaired by the endonuclease II-polymerase I excision-repair system.", "contents": "Involvement of separate pathways in the repair of mutational and lethal lesions induced by a monofunctional sulfur mustard. The mutagenic and lethal effects of a monofunctional sulfur mustard, 2-chloro-ethylethylsulfide (CEES), have been studied in a number of repair deficient variants of Escherichia coli K12, B/r and B. The results indicate that CEES induces a (pre)mutational lesion which is subject to Uvr+-excision-repair. Extensive CEES-induced mutagenesis can occur in exrA- uvrA- and recA- uvrB- variants suggesting that the majority of the mutations in Uvr-bacteria do not arise from error-prone repair. These findings are similar to results previously reported with a volatile degradation product of captan and with ethyl methanesulfonate (EMS) but differ from those reported with methyl methanesulfonate (MMS). It is hypothesized that CEES alkylates guanine at the O-6 position (R-O-6-G) and that this R-O-6-G which is Uvr+-excisable is directly mutagenic by producing G-C to A-T transitions during replication. Reduced levels of induced mutation frequencies observed in an endonuclease II-deficient variant lead us to postulate that, in constrast to Uvr- bacteria, CEES-induced mutation in wild-type cells arise from error-prone repair of apurinic sites. Analysis of the lethal actions of CEES indicates that the lesion produced is largely unexcisable by the Uvr+ system. Host-cell reactivation of CEES-treated TI bacteriophage shows that the production of the (pre)ethal lesion is dependent on both the initial dose and post-treatment incubation. The efficient repair of the (pre)ethal lesion requires both endonuclease II and polymerase I. Moreover, deficiencies of these two enzymes rendered bacteria more sensitive to the cytotoxic action of CEES. It is postulated that the lethal mechanism of CEES involves: (I) alkylation at the N-3 position of adenine and the N-7 position of guanine; (2) spontaneous depurination of these alkylated bases; and (3) production of apurinic sites which are lethal unless repaired by the endonuclease II-polymerase I excision-repair system."} {"id": "PMID:166306", "title": "Reversions of the two missense and one nonsense trp-mutations induced by UV-light or methyl methanesulfonate in E. coli wild type and its polAi and uvrE502 mutants.", "content": "Two missense mutations, trpA58 and trpA78, and one nonsense mutation-trp-ochre, were used to determine the types of base-pair substitution caused by ultra, violet irradiation and methyl methanesulfonate (MMS) in Escherichia coli. UV irradiation of the wild-type bacteria led to the formation of revertants mainly arising as a result of GC yields AT transitions (suppressor revertants of the trpA58 mutant). True revertants of the trp- mutant (arising via transitions of AT pairs) and 5-methyl tryptophan-sensitive (MT-s) Trp+ of the trpA78 mutant (arising via unidentified transversions) occurred at a lower frequency. The polAI mutation did not change the frequency of the UV-induced transitions GC yields AT or that of the substitutions of the AT pairs. The uvrE502 mutation significantly increased the frequency of the UV-induced revertants arising via the transition GC yields AT. Treatment of the wild-type bacteria with MMS resulted in the formation of revertants mainly due to the GC yields AT substitution, and with a lower frequency to the AT yields GC transitions. MMS also induced, with a low frequency, some transversions. The frequency of the MMS-induced GC yields AT transitions was enhanced in the uvrE502 mutant. On the other hand, the uvrE502 mutation eliminated or significantly lowered MMS-induced revertants arising as a result of AT yields GC transitions or transversions.", "contents": "Reversions of the two missense and one nonsense trp-mutations induced by UV-light or methyl methanesulfonate in E. coli wild type and its polAi and uvrE502 mutants. Two missense mutations, trpA58 and trpA78, and one nonsense mutation-trp-ochre, were used to determine the types of base-pair substitution caused by ultra, violet irradiation and methyl methanesulfonate (MMS) in Escherichia coli. UV irradiation of the wild-type bacteria led to the formation of revertants mainly arising as a result of GC yields AT transitions (suppressor revertants of the trpA58 mutant). True revertants of the trp- mutant (arising via transitions of AT pairs) and 5-methyl tryptophan-sensitive (MT-s) Trp+ of the trpA78 mutant (arising via unidentified transversions) occurred at a lower frequency. The polAI mutation did not change the frequency of the UV-induced transitions GC yields AT or that of the substitutions of the AT pairs. The uvrE502 mutation significantly increased the frequency of the UV-induced revertants arising via the transition GC yields AT. Treatment of the wild-type bacteria with MMS resulted in the formation of revertants mainly due to the GC yields AT substitution, and with a lower frequency to the AT yields GC transitions. MMS also induced, with a low frequency, some transversions. The frequency of the MMS-induced GC yields AT transitions was enhanced in the uvrE502 mutant. On the other hand, the uvrE502 mutation eliminated or significantly lowered MMS-induced revertants arising as a result of AT yields GC transitions or transversions."} {"id": "PMID:166307", "title": "Mutagenesis by nitrosoguanidine, ethyl methanesulfonate, and mutator gene mutH in continuous cultures of Escherichia coli.", "content": "Induction of T5-R mutations by alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and ethyl methanesulfonate (EMS) was examined in glucose limited chemostat cultures of non-mutator and mutator (mutH) bacteria. In agreement with the proposal that NTG mutagenizes DNA at the replication fork, this mutagen (6.8 X 10-minus 6 M) showed replication-dependent mutagenesis in continuous culture. EMS (5-10-minus M)) induced mutagenesis could not be correlated with growth rate, which probably means that induction of mutagenic lesions (promutations) by this mutagen does not involve replicating genes. A large synergic response was found for the mutH gene in combination with NTG, supporting the hypothesis that the mutH gene product acts during DNA replication.", "contents": "Mutagenesis by nitrosoguanidine, ethyl methanesulfonate, and mutator gene mutH in continuous cultures of Escherichia coli. Induction of T5-R mutations by alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and ethyl methanesulfonate (EMS) was examined in glucose limited chemostat cultures of non-mutator and mutator (mutH) bacteria. In agreement with the proposal that NTG mutagenizes DNA at the replication fork, this mutagen (6.8 X 10-minus 6 M) showed replication-dependent mutagenesis in continuous culture. EMS (5-10-minus M)) induced mutagenesis could not be correlated with growth rate, which probably means that induction of mutagenic lesions (promutations) by this mutagen does not involve replicating genes. A large synergic response was found for the mutH gene in combination with NTG, supporting the hypothesis that the mutH gene product acts during DNA replication."} {"id": "PMID:166311", "title": "Association of an isomeric species of carcinoembryonic antigen with neoplasia of the gastrointestinal tract.", "content": "We studied the association between serum levels of an isomeric species of carcinoembryonic antigen and neoplasia of the gastrointestinal tract in 993 patients. With use of an empirically determined threshold, the antigen was found to be elevated in 80.4 per cent of 138 patients with neof other tumors, predominantly lung and breast tumors. Serum levels were elevated in 0.23 per cent of random patients and 0.41 per cent of 725 patients without neoplasia, including those with liver diseases, inflammatory bowel disease and chronic renal disease. The results of this study suggest that this species of carcinoembryonic antigen, and that assay for it offers an improved approach to the diagnosis and management of neoplasia of the gastroinetestinal tract.", "contents": "Association of an isomeric species of carcinoembryonic antigen with neoplasia of the gastrointestinal tract. We studied the association between serum levels of an isomeric species of carcinoembryonic antigen and neoplasia of the gastrointestinal tract in 993 patients. With use of an empirically determined threshold, the antigen was found to be elevated in 80.4 per cent of 138 patients with neof other tumors, predominantly lung and breast tumors. Serum levels were elevated in 0.23 per cent of random patients and 0.41 per cent of 725 patients without neoplasia, including those with liver diseases, inflammatory bowel disease and chronic renal disease. The results of this study suggest that this species of carcinoembryonic antigen, and that assay for it offers an improved approach to the diagnosis and management of neoplasia of the gastroinetestinal tract."} {"id": "PMID:166313", "title": "Elevated plasma and tissue levels of vasoactive intestinal polypeptide in the watery-diarrhea syndrome due to pancreatic, bronchogenic and other tumors.", "content": "The actions of the vasoactive intestinal polypeptide make it a potential candidate for mediating certain manifestations of the watery-diarrhea syndrome. Peptide levels were measured by radioimmunoassay in 25 controls and 30 patients with chronic watery diarrhea. Plasma levels were too low to measure (smaller 200 pg per milliliter) in 22 of the controls, averaging 79 plus or minus 64 pg per milliliter (S.D.). Levels were elevated in 26 of 28 plasma samples (5.1 plus or minus 2.5 ng per milliliter), and in each of 13 tissue extracts (5.1 plus or minus 10.9 mug per gram); in all, 28 patients had elevated levels in plasma or tissue or both. Thirteen patients had pancreatic islet-cell adenoma, four islet-cell hyperplasia, five bronchogenic carcinoma, and one each pheochromocytoma and ganglioneuroblastoma. The findings indicate that the peptide is a probable mediator of the watery-diarrhea syndrome, that the syndrome may result from a variety of non-pancreatic tumors, and that this or a related peptide may also be secreted by these tumors.", "contents": "Elevated plasma and tissue levels of vasoactive intestinal polypeptide in the watery-diarrhea syndrome due to pancreatic, bronchogenic and other tumors. The actions of the vasoactive intestinal polypeptide make it a potential candidate for mediating certain manifestations of the watery-diarrhea syndrome. Peptide levels were measured by radioimmunoassay in 25 controls and 30 patients with chronic watery diarrhea. Plasma levels were too low to measure (smaller 200 pg per milliliter) in 22 of the controls, averaging 79 plus or minus 64 pg per milliliter (S.D.). Levels were elevated in 26 of 28 plasma samples (5.1 plus or minus 2.5 ng per milliliter), and in each of 13 tissue extracts (5.1 plus or minus 10.9 mug per gram); in all, 28 patients had elevated levels in plasma or tissue or both. Thirteen patients had pancreatic islet-cell adenoma, four islet-cell hyperplasia, five bronchogenic carcinoma, and one each pheochromocytoma and ganglioneuroblastoma. The findings indicate that the peptide is a probable mediator of the watery-diarrhea syndrome, that the syndrome may result from a variety of non-pancreatic tumors, and that this or a related peptide may also be secreted by these tumors."} {"id": "PMID:166327", "title": "A correlated study of kidney function and ultrastructure in potassium-depleted rats.", "content": "In order to provide an ultrastructural description of kaliopenic nephropathy in rats, potassium deficiency uncomplicated by chloride depletion or extracellular fluid volume expansion was induced by dietary means alone. After 12 days, serum and muscle analyses demonstrated severe potassium depletion, while urine concentrating ability was markedly impaired. Although micropuncture techniques demonstrated that net fluid transport in proximal tubules was normal, the epithelial cells showed the following morphological alterations: electron-lucent vacuoles and lysosome-like dense bodies were numerous, focal cytoplasmic degradation was present, and intercellular spaces were dilated in many proximal tubules. Medullary cell droplets were characterized by fusion, massive enlargement with sequestration of cytoplasmic components such as ribosomes, and occasional extrusion through ruptured plasma membranes--features not previously reported.", "contents": "A correlated study of kidney function and ultrastructure in potassium-depleted rats. In order to provide an ultrastructural description of kaliopenic nephropathy in rats, potassium deficiency uncomplicated by chloride depletion or extracellular fluid volume expansion was induced by dietary means alone. After 12 days, serum and muscle analyses demonstrated severe potassium depletion, while urine concentrating ability was markedly impaired. Although micropuncture techniques demonstrated that net fluid transport in proximal tubules was normal, the epithelial cells showed the following morphological alterations: electron-lucent vacuoles and lysosome-like dense bodies were numerous, focal cytoplasmic degradation was present, and intercellular spaces were dilated in many proximal tubules. Medullary cell droplets were characterized by fusion, massive enlargement with sequestration of cytoplasmic components such as ribosomes, and occasional extrusion through ruptured plasma membranes--features not previously reported."} {"id": "PMID:166330", "title": "Cytoplasmic inclusion bodies in superior rectus muscle of the eye.", "content": "Cytoplasmic inclusion bodies are found in fibers of superior rectus muscle of the eye. They occur in middle-aged and old individuals dying with various unrelated diseases not affecting muscle and in patients with myotonic dystrophy. With light microscopy they can be observed in fibers with pathologic changes, and with electron microscopy they appear to be associated with crystals of probable viral origin. It is suggested that cytoplasmic inclusion bodies in superior rectus muscle are the result of viral activity and may represent an incidental viral infection of the senescent period.", "contents": "Cytoplasmic inclusion bodies in superior rectus muscle of the eye. Cytoplasmic inclusion bodies are found in fibers of superior rectus muscle of the eye. They occur in middle-aged and old individuals dying with various unrelated diseases not affecting muscle and in patients with myotonic dystrophy. With light microscopy they can be observed in fibers with pathologic changes, and with electron microscopy they appear to be associated with crystals of probable viral origin. It is suggested that cytoplasmic inclusion bodies in superior rectus muscle are the result of viral activity and may represent an incidental viral infection of the senescent period."} {"id": "PMID:166331", "title": "A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity?", "content": "A 13-year-old girl showed periodic episodes of somnolence without megaphagia recurring in association with each menstruation. During somnolent episodes total sleep time averaged 14 hours and 19 minutes per 24 hours. The level of performance evaluated by means of the Wilkinson Addition Test was significantly impaired. There was an abnormal increase of 5-hydroxyindolacetic acid in the cerebrospinal fluid after probenecid test, suggesting an increase of the turnover of 5-hydroxytryptamine during periodic hypersomnia. Investigation of the menstrual cycle failed to document any striking hormonal abnormality. Nevertheless, the close relationship between the episodes of hypersomnia and the end of the menstrual cycle led us to hypothesize a role of progesterone and to try a hormonal type of treatment that is thus far successful.", "contents": "A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity? A 13-year-old girl showed periodic episodes of somnolence without megaphagia recurring in association with each menstruation. During somnolent episodes total sleep time averaged 14 hours and 19 minutes per 24 hours. The level of performance evaluated by means of the Wilkinson Addition Test was significantly impaired. There was an abnormal increase of 5-hydroxyindolacetic acid in the cerebrospinal fluid after probenecid test, suggesting an increase of the turnover of 5-hydroxytryptamine during periodic hypersomnia. Investigation of the menstrual cycle failed to document any striking hormonal abnormality. Nevertheless, the close relationship between the episodes of hypersomnia and the end of the menstrual cycle led us to hypothesize a role of progesterone and to try a hormonal type of treatment that is thus far successful."} {"id": "PMID:166332", "title": "Studies on the antiparkinsonism efficacy of lergotrile.", "content": "The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.", "contents": "Studies on the antiparkinsonism efficacy of lergotrile. The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients."} {"id": "PMID:166342", "title": "Radiologic features of benign pleomorphic adenoma of the hard palate.", "content": "The clinical and radiographic features of two cases of pleomorphic adenoma are discussed. With the use of hypocycloidal tomography, definitive radiographic signs of benignity are demonstrated. They include (1) a radiolucent defect with well-defined cortical margins; (2) beveled margins which describe an intraoral origin of the neoplasm; (3) confinement of the neoplasm within the actual osseous defect, or within the projected circumferential diameter of the defect, if complete erosion has occurred; and (4) lack of periosteal reaction or osseous involvement of the hard palate adjacent to the radiolucent defect.", "contents": "Radiologic features of benign pleomorphic adenoma of the hard palate. The clinical and radiographic features of two cases of pleomorphic adenoma are discussed. With the use of hypocycloidal tomography, definitive radiographic signs of benignity are demonstrated. They include (1) a radiolucent defect with well-defined cortical margins; (2) beveled margins which describe an intraoral origin of the neoplasm; (3) confinement of the neoplasm within the actual osseous defect, or within the projected circumferential diameter of the defect, if complete erosion has occurred; and (4) lack of periosteal reaction or osseous involvement of the hard palate adjacent to the radiolucent defect."} {"id": "PMID:166343", "title": "Effects of ionizing radiation on dried spores of Osmunda regalis III. 35 GHz e.s.r. study.", "content": "The use of 35 GHz microwave frequency has greatly simplified the separation of overlapping signals in dried irradiated fern spores. While in general confirming the conclusions previously drawn from X-band spectra, the use of Q-band has clarified several assignments of radical groups and allowed the recognition of additional radical groups or sub-groups.", "contents": "Effects of ionizing radiation on dried spores of Osmunda regalis III. 35 GHz e.s.r. study. The use of 35 GHz microwave frequency has greatly simplified the separation of overlapping signals in dried irradiated fern spores. While in general confirming the conclusions previously drawn from X-band spectra, the use of Q-band has clarified several assignments of radical groups and allowed the recognition of additional radical groups or sub-groups."} {"id": "PMID:166347", "title": "The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure.", "content": "Rats treated for 7 days with reserpine develop structural changes in the submaxillary gland that resemble those that have been reported in cystic fibrosis. The salivary exocrinopathy is characterized by increased amounts of PAS-reactive mucoprotein in the acinar cells and by obstruction and dilatation of ducts by precipitated material with the same staining characteristics as those found in the acinar elements.", "contents": "The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure. Rats treated for 7 days with reserpine develop structural changes in the submaxillary gland that resemble those that have been reported in cystic fibrosis. The salivary exocrinopathy is characterized by increased amounts of PAS-reactive mucoprotein in the acinar cells and by obstruction and dilatation of ducts by precipitated material with the same staining characteristics as those found in the acinar elements."} {"id": "PMID:166348", "title": "Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity.", "content": "Six subjects from three sibships with hyperornithinemia, homocitrullinuria, and hyperammonemia are described. Assays of liver biopsy in one showed decreased CPS I and leukocyte assays indicate a similar defect in all six. Loading studies with ornithine and citrulline are consistent with a block early in the urea cycle between ornithine and citrulline. They thus support the results of the enzymatic assays. Similar studies with lysine and homocitrulline indicate there is excessive homocitrulline biosynthesis that is related to lysine intake, but there is no evidence of a block in the main lysine catabolic pathway. The younger more severely affected patients require protein restriction to 1.2 and 1.5 g/kg/24 hr to control hyperammonemia; hyperornithinemia remains unaffected. Adult subjects avoid large protein meals but tolerate a diet that is almost normal. The mode of inheritance of this disorder appears to be autosomal recessive. The fine structure of liver shows the presence of large and abnormally configurated mitochondria. There is a peculiar periodic structure situated closely to the inner mitochondrial membrane, and it is possible that the presence of this may be related to the impairment of transport of ornithine into the mitochondria; this in turn may give rise to hyperornithinemia. This disorder adds to the metabolic errors that suggest that there are close links of lysine metabolism to the urea cycle but the details are yet to be defined.", "contents": "Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity. Six subjects from three sibships with hyperornithinemia, homocitrullinuria, and hyperammonemia are described. Assays of liver biopsy in one showed decreased CPS I and leukocyte assays indicate a similar defect in all six. Loading studies with ornithine and citrulline are consistent with a block early in the urea cycle between ornithine and citrulline. They thus support the results of the enzymatic assays. Similar studies with lysine and homocitrulline indicate there is excessive homocitrulline biosynthesis that is related to lysine intake, but there is no evidence of a block in the main lysine catabolic pathway. The younger more severely affected patients require protein restriction to 1.2 and 1.5 g/kg/24 hr to control hyperammonemia; hyperornithinemia remains unaffected. Adult subjects avoid large protein meals but tolerate a diet that is almost normal. The mode of inheritance of this disorder appears to be autosomal recessive. The fine structure of liver shows the presence of large and abnormally configurated mitochondria. There is a peculiar periodic structure situated closely to the inner mitochondrial membrane, and it is possible that the presence of this may be related to the impairment of transport of ornithine into the mitochondria; this in turn may give rise to hyperornithinemia. This disorder adds to the metabolic errors that suggest that there are close links of lysine metabolism to the urea cycle but the details are yet to be defined."} {"id": "PMID:166349", "title": "The effect of exogenous 3':5'-adenosine monophosphate on urinary output in children with vasopressin-resistant diabetes insipidus.", "content": "The administration of c-AMP and DB c-AMP to six children with NDI has failed to yield an antidiuretic effect. From the present study it may be concluded that, at the doses used, neither c-AMP nor its dibutyryl derivative can mimic the action of ADH in NDI as they do in normal subjects. On the contrary, DB c-AMP increased urine volume and Cosm in a very marked way, without changing the creatinine excretion.", "contents": "The effect of exogenous 3':5'-adenosine monophosphate on urinary output in children with vasopressin-resistant diabetes insipidus. The administration of c-AMP and DB c-AMP to six children with NDI has failed to yield an antidiuretic effect. From the present study it may be concluded that, at the doses used, neither c-AMP nor its dibutyryl derivative can mimic the action of ADH in NDI as they do in normal subjects. On the contrary, DB c-AMP increased urine volume and Cosm in a very marked way, without changing the creatinine excretion."} {"id": "PMID:166353", "title": "[Acute bovine mastitis caused by clostridium perfringens type A (Author's transl.)].", "content": "An acute case of bovine mastitis caused by clostridium perfringens type A is described. The condition appeared before delivery and was characterised by gas formation in the udder and severe general signs. In spite of parenteral treatment with large doses of penicillin and streptomycin combined with frequent stripping of the udder the animal died two days after the onset of symptoms. The strain isolated proved sensitive to penicillin, chloramphenicol and tetracyclin, but resistant to streptomycin and sulphonamides.", "contents": "[Acute bovine mastitis caused by clostridium perfringens type A (Author's transl.)]. An acute case of bovine mastitis caused by clostridium perfringens type A is described. The condition appeared before delivery and was characterised by gas formation in the udder and severe general signs. In spite of parenteral treatment with large doses of penicillin and streptomycin combined with frequent stripping of the udder the animal died two days after the onset of symptoms. The strain isolated proved sensitive to penicillin, chloramphenicol and tetracyclin, but resistant to streptomycin and sulphonamides."} {"id": "PMID:166362", "title": "Horizontal transmission of turkey herpesvirus to chickens. 3. Transmission in three different lines of chickens.", "content": "Horizontal transmission of turkey herpesvirus (HVT) was studied in three separate trials using three different lines of chickens in each trial. There was no horizontal spread of HVT to contact cagemates through 8 weeks regardless of the line of donor chickens, when inoculated subcutaneously with 9.2 times 10-3 plaque-forming units (PFU) of HVT at 1 week of age. The virus spread poorly to a few cagemates from an experimental line of White Leghorns (W.S.U.-V.S.), but not from a commercial line of White Leghorns (C.-W.L.) or meat-type (C.-M.T.) chickens, when inoculated with 9.4 times 10-4 PFU of HVT at 1 week of age. The virus spread readily to contact cagemates from W.S.U.-V.S. but not at all from C.-W.L. or C.-M.T. chickens when inoculated with 2 times 10-4 PFU of HVT at 8 weeks of age. The incidence among cagemates of contact infection by HVT appeared similar regardless of genetic lines. This observation indicated a difference among different genetic lines of chickens in the development and/or shedding of infectious HVT following virus inoculation.", "contents": "Horizontal transmission of turkey herpesvirus to chickens. 3. Transmission in three different lines of chickens. Horizontal transmission of turkey herpesvirus (HVT) was studied in three separate trials using three different lines of chickens in each trial. There was no horizontal spread of HVT to contact cagemates through 8 weeks regardless of the line of donor chickens, when inoculated subcutaneously with 9.2 times 10-3 plaque-forming units (PFU) of HVT at 1 week of age. The virus spread poorly to a few cagemates from an experimental line of White Leghorns (W.S.U.-V.S.), but not from a commercial line of White Leghorns (C.-W.L.) or meat-type (C.-M.T.) chickens, when inoculated with 9.4 times 10-4 PFU of HVT at 1 week of age. The virus spread readily to contact cagemates from W.S.U.-V.S. but not at all from C.-W.L. or C.-M.T. chickens when inoculated with 2 times 10-4 PFU of HVT at 8 weeks of age. The incidence among cagemates of contact infection by HVT appeared similar regardless of genetic lines. This observation indicated a difference among different genetic lines of chickens in the development and/or shedding of infectious HVT following virus inoculation."} {"id": "PMID:166363", "title": "Distribution studies of glycine and serine enzymes in chicks.", "content": "Day-old broiler type chicks were fed a practical starter ration for three weeks, sacrificed and the D-3-phosphoglycerate dehydrogenase (E.C.1.1.1.s), phosphoserine phosphatase (E.C.3.1.3.3.), glycerate dehydrogenase (E.C.1.1.1.29), hydroxypyruvate-P: glutamate transaminase, serine transhydroxymethylase (E.C.2.1.2.1), and serine dehydratase (E.C.4.2.1.13) enzyme activities were determined in liver, kidney, heart, spleen and brain tissue in evaluating glycine and serine metabolism. The distribution of the various glycine and serine biosynthetic enzymes in the chick tissues studied show that the major portion of glycine and serine synthesis occurs in hepatic tissue via the \"phosphorylated pathway\".", "contents": "Distribution studies of glycine and serine enzymes in chicks. Day-old broiler type chicks were fed a practical starter ration for three weeks, sacrificed and the D-3-phosphoglycerate dehydrogenase (E.C.1.1.1.s), phosphoserine phosphatase (E.C.3.1.3.3.), glycerate dehydrogenase (E.C.1.1.1.29), hydroxypyruvate-P: glutamate transaminase, serine transhydroxymethylase (E.C.2.1.2.1), and serine dehydratase (E.C.4.2.1.13) enzyme activities were determined in liver, kidney, heart, spleen and brain tissue in evaluating glycine and serine metabolism. The distribution of the various glycine and serine biosynthetic enzymes in the chick tissues studied show that the major portion of glycine and serine synthesis occurs in hepatic tissue via the \"phosphorylated pathway\"."} {"id": "PMID:166364", "title": "Effect of regression of Rous sarcoma tumors upon egg production in an inbred line of White Leghorns.", "content": "Reserach was conducted to determine whether development and subsequent regression of a Rous sarcoma virus (RSV) induced wing-web tumor influenced egg production. Fifty-seven six-week old pullet chicks of inbred line 6 of the United States Department of Agriculture, Regional Poultry Research Laboratory, East Lansing, Michigan, were inoculated subcutaneously in the left wing-web with 0.1 ml. of a 10-minus 3 dilution of a pseudotype of Bryan high titer RSV designated BH-RSV (RAV-1). Thirty chicks were left uninoculated. Each chick was examined for tumor growth at regular intervals to 10 weeks post-inoculation. A tumor was considered regressed if it disappeared completely. Ninteen regressor and 22 uninoculated females were placed in laying cages at 4.5 months of age and egg production data obtained over seven 28-day periods. The difference in hen-day egg production between regressors and uninoculated controls favored regressors by 2.7 eggs/bird and was statistically significant. Physiological stimulus from cellular immunity, linkage and pleiotropy are discussed as possible caused of the higher egg production in regressors.", "contents": "Effect of regression of Rous sarcoma tumors upon egg production in an inbred line of White Leghorns. Reserach was conducted to determine whether development and subsequent regression of a Rous sarcoma virus (RSV) induced wing-web tumor influenced egg production. Fifty-seven six-week old pullet chicks of inbred line 6 of the United States Department of Agriculture, Regional Poultry Research Laboratory, East Lansing, Michigan, were inoculated subcutaneously in the left wing-web with 0.1 ml. of a 10-minus 3 dilution of a pseudotype of Bryan high titer RSV designated BH-RSV (RAV-1). Thirty chicks were left uninoculated. Each chick was examined for tumor growth at regular intervals to 10 weeks post-inoculation. A tumor was considered regressed if it disappeared completely. Ninteen regressor and 22 uninoculated females were placed in laying cages at 4.5 months of age and egg production data obtained over seven 28-day periods. The difference in hen-day egg production between regressors and uninoculated controls favored regressors by 2.7 eggs/bird and was statistically significant. Physiological stimulus from cellular immunity, linkage and pleiotropy are discussed as possible caused of the higher egg production in regressors."} {"id": "PMID:166365", "title": "A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 1. incorporation of I-131 in chicken ova.", "content": "The uptake of 131-I in chicken ova was studied for 3 hours after a single intramuscular dose. There was uptake as early as 10 minutes and it continued throughout the 3 hours in spite of a rapid decrease in blood activity. The fast growing ova, weightin 0.5 to 2.0 grams, were the most efficient in the uptake of 131-I per unit weight. Autoradiograms of the topographic distribution of 131-I showed a peripheral deposition. When multiple doses were given, concentric rings in the growing ovocytes were seen.", "contents": "A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 1. incorporation of I-131 in chicken ova. The uptake of 131-I in chicken ova was studied for 3 hours after a single intramuscular dose. There was uptake as early as 10 minutes and it continued throughout the 3 hours in spite of a rapid decrease in blood activity. The fast growing ova, weightin 0.5 to 2.0 grams, were the most efficient in the uptake of 131-I per unit weight. Autoradiograms of the topographic distribution of 131-I showed a peripheral deposition. When multiple doses were given, concentric rings in the growing ovocytes were seen."} {"id": "PMID:166366", "title": "The effect of diet on the severity of losses from infectious bursal disease (Gumboro) in a commercial broiler genetype.", "content": "A natural outbreak of infectious bursal disease occurred in an experimental broiler flock being reared on 3 starter diets having 18.8, 21.6 and 24.0 per cent protein. Groups fed the highest protein starter exhibited significantly higher mortality and had larger numbers of stunted birds.", "contents": "The effect of diet on the severity of losses from infectious bursal disease (Gumboro) in a commercial broiler genetype. A natural outbreak of infectious bursal disease occurred in an experimental broiler flock being reared on 3 starter diets having 18.8, 21.6 and 24.0 per cent protein. Groups fed the highest protein starter exhibited significantly higher mortality and had larger numbers of stunted birds."} {"id": "PMID:166367", "title": "Antibody response of genetically susceptible and resistant chickens to cell-free and attenuated JM-V leukosis strain and its influence on early type II (Marek's) leukosis infection.", "content": "Experiments were carried out to: 1) determine the antibody response of chickens to cell-free and attenuated preparations of JMV leukosis strain, 2) determine the differences in antibody response to these antigens between susceptible (P-line) and resistant (N-line) chickens by means of serum neutralization and indirect fluorescent antibody tests, 3) investigate the influence of maternal (passive) antibody on early (day-old) JMV vaccination and 4) investigate the influence of maternal antibody in chicks naturally exposed continuously to JM virus from day-old to 8 weeks of age on the pathogenesis of Type II leudosis (Marek's) infections and oncogenesis.", "contents": "Antibody response of genetically susceptible and resistant chickens to cell-free and attenuated JM-V leukosis strain and its influence on early type II (Marek's) leukosis infection. Experiments were carried out to: 1) determine the antibody response of chickens to cell-free and attenuated preparations of JMV leukosis strain, 2) determine the differences in antibody response to these antigens between susceptible (P-line) and resistant (N-line) chickens by means of serum neutralization and indirect fluorescent antibody tests, 3) investigate the influence of maternal (passive) antibody on early (day-old) JMV vaccination and 4) investigate the influence of maternal antibody in chicks naturally exposed continuously to JM virus from day-old to 8 weeks of age on the pathogenesis of Type II leudosis (Marek's) infections and oncogenesis."} {"id": "PMID:166369", "title": "[The functional state of the adrenal cortex in patients with gonadal dysgenesis and a female phenotype].", "content": "Excretion of 17-KS and 17-OCS was studied in the urine of 86 patients with various cytogenetic variants of gonad dysgenesis of a female phenotype under basic conditions and after ACTH stimulation; in 10 patients endogenous hypophyseal ACTH reserve after block of the adrenal cortex by metopyrone was investigated as well. A conclusion was drawn on the presence in these patients of differnet types of deviations of the adrenal gland function. In some of the cases there is a primary \"global\" or dissociated injury of the adrenal cortex, apparently directly associated with gonosome anomaly; in other cases--with disturbed regulation of ACTH secretion.", "contents": "[The functional state of the adrenal cortex in patients with gonadal dysgenesis and a female phenotype]. Excretion of 17-KS and 17-OCS was studied in the urine of 86 patients with various cytogenetic variants of gonad dysgenesis of a female phenotype under basic conditions and after ACTH stimulation; in 10 patients endogenous hypophyseal ACTH reserve after block of the adrenal cortex by metopyrone was investigated as well. A conclusion was drawn on the presence in these patients of differnet types of deviations of the adrenal gland function. In some of the cases there is a primary \"global\" or dissociated injury of the adrenal cortex, apparently directly associated with gonosome anomaly; in other cases--with disturbed regulation of ACTH secretion."} {"id": "PMID:166370", "title": "[The clinical value of contrast-less mammography in endocrine diseases].", "content": "The authors analyze the X-ray picture of the changes occurring in the mammary glands in women with various endocrine diseases and in men with gynecomastia. Contrastless mammagraphy was carried out in 189 persons. In studying the mammagrams in patients with endocrine diseases assessment was made of the state of the subcutaneous-adipose cellular tissue, total dimensions of the organ. The majority of the endocrine diseases were accompanied at the initial stages of their development by changes in the endocrine gland, this serving as a direct indication for the use of contrastless roentgenography for the purpose of earlier and proper choice of the therapeutic method.", "contents": "[The clinical value of contrast-less mammography in endocrine diseases]. The authors analyze the X-ray picture of the changes occurring in the mammary glands in women with various endocrine diseases and in men with gynecomastia. Contrastless mammagraphy was carried out in 189 persons. In studying the mammagrams in patients with endocrine diseases assessment was made of the state of the subcutaneous-adipose cellular tissue, total dimensions of the organ. The majority of the endocrine diseases were accompanied at the initial stages of their development by changes in the endocrine gland, this serving as a direct indication for the use of contrastless roentgenography for the purpose of earlier and proper choice of the therapeutic method."} {"id": "PMID:166375", "title": "Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells.", "content": "Host cell and virus-specific poly(A)-containing RNAs isolated from nuclei and cytoplasm of monkey kidney cells infected with simian virus 40 contain different methylated nucleotides. In the cytoplasmic simian virus 40-specific RNA, about 75% of the radioactivity derived from (methyl-3-H)methionine was in N-6-methyladenosine (N-6mA) after digestion with Penicillium nuclease and bacterial alkaline phosphatase. The remainder was in a negatively charge component with properties of 5'-terminal structures, i.e., digestion with nucleotide pyrophosphatase and bacterial alkaline phosphatase released 2'-O-methyladenosine (A-m), 2'-O-methylguanosine (G-m), and 7-methylguanosine (m-7-G), consistent with a 5'-terminal structure of the type, m7-GpppNm. The nuclear virus-specific RNA contained N6mA, GM, 2'-O-methyluridine (U-m), and a smaller proportion (10%) of nuclease-, phosphatase-resistant presumptive 5' termini that also yielded A-m, G-m, and m7-G upon further hydrolysis. The infected cell nuclear and cytoplasmic RNAs that did not hybridize to DNA of simian virus 40 contained all four 2'-O-methylnucleosides. The possible role of methylation in the processing and translation of simian virus 40-specific mRNA is discussed.", "contents": "Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells. Host cell and virus-specific poly(A)-containing RNAs isolated from nuclei and cytoplasm of monkey kidney cells infected with simian virus 40 contain different methylated nucleotides. In the cytoplasmic simian virus 40-specific RNA, about 75% of the radioactivity derived from (methyl-3-H)methionine was in N-6-methyladenosine (N-6mA) after digestion with Penicillium nuclease and bacterial alkaline phosphatase. The remainder was in a negatively charge component with properties of 5'-terminal structures, i.e., digestion with nucleotide pyrophosphatase and bacterial alkaline phosphatase released 2'-O-methyladenosine (A-m), 2'-O-methylguanosine (G-m), and 7-methylguanosine (m-7-G), consistent with a 5'-terminal structure of the type, m7-GpppNm. The nuclear virus-specific RNA contained N6mA, GM, 2'-O-methyluridine (U-m), and a smaller proportion (10%) of nuclease-, phosphatase-resistant presumptive 5' termini that also yielded A-m, G-m, and m7-G upon further hydrolysis. The infected cell nuclear and cytoplasmic RNAs that did not hybridize to DNA of simian virus 40 contained all four 2'-O-methylnucleosides. The possible role of methylation in the processing and translation of simian virus 40-specific mRNA is discussed."} {"id": "PMID:166372", "title": "[Participation of cerebral dopamine receptors in activating the endocrine function of the male sex glands].", "content": "One hour after the administration of 10 gamma of dopamine into the third ventricle of the brain to male albino rate the level of testosterone in the peripheral blood plasma (determined fluorimetrically) proved to double. Such effect was absent against the background of complete postero-lateral or posterior deafferentation of the meidal-basal area of the hypothalamus (MBAH). Section of the anterior nervous connections of the MBAH with the preoptic region failed to prevent the stimulating action of dopamine administered into the ventricle: blood testosterone level doubled as in the rats with an intact hypothalamus. A conclusion was made that dopamine receptors associated with the endocrine function of the male gonad were located outside the MBAH. Nervous tracts conducting this excitation reached the hypophyseotrophic zone of the hypothalamus through its posterior connections.", "contents": "[Participation of cerebral dopamine receptors in activating the endocrine function of the male sex glands]. One hour after the administration of 10 gamma of dopamine into the third ventricle of the brain to male albino rate the level of testosterone in the peripheral blood plasma (determined fluorimetrically) proved to double. Such effect was absent against the background of complete postero-lateral or posterior deafferentation of the meidal-basal area of the hypothalamus (MBAH). Section of the anterior nervous connections of the MBAH with the preoptic region failed to prevent the stimulating action of dopamine administered into the ventricle: blood testosterone level doubled as in the rats with an intact hypothalamus. A conclusion was made that dopamine receptors associated with the endocrine function of the male gonad were located outside the MBAH. Nervous tracts conducting this excitation reached the hypophyseotrophic zone of the hypothalamus through its posterior connections."} {"id": "PMID:166373", "title": "[The state of the peripheral endocrine glands 14 months following hypophysectomy and their sensitivity to the tropic hormones of the hypophysis].", "content": "Rats hypophysectomized at the age of four weeks continued to grow at a delayed rate during the whole fourteen month's observation period. A spontaneous development of the sexual apparatus was noted in some of the hypophysectomized animals: an increase in the weight of the testes, of the ventral prostate and of the seminal vesicles. In fourteen months the peripheral endocrine glands retained their sensitivity to the tropic hormones of the hypophysis; a ten-day adminstration of a corresponding tropic hormone led to a double increase in weight of the dependent endocrine gland and a sharp elevation of its functional activity.", "contents": "[The state of the peripheral endocrine glands 14 months following hypophysectomy and their sensitivity to the tropic hormones of the hypophysis]. Rats hypophysectomized at the age of four weeks continued to grow at a delayed rate during the whole fourteen month's observation period. A spontaneous development of the sexual apparatus was noted in some of the hypophysectomized animals: an increase in the weight of the testes, of the ventral prostate and of the seminal vesicles. In fourteen months the peripheral endocrine glands retained their sensitivity to the tropic hormones of the hypophysis; a ten-day adminstration of a corresponding tropic hormone led to a double increase in weight of the dependent endocrine gland and a sharp elevation of its functional activity."} {"id": "PMID:166376", "title": "Immunohistochemical localization of 3': 5'-cyclic AMP and 3': 5'-cyclic GMP in rat liver, intestine, and testis.", "content": "Cyclic GMP and cyclic AMP have been localized in rat liver, small intestine, and testis by a fluorescent immunocytochemical procedure. In liver, cyclic AMP is distributed along sinusoids predominantly, and increased fluorescence is seen sinusoidal areas after glucagon administration. Cyclic GMP is located in nuclear elements and on the plasma membranes of hepatocytes. In jejunum, cyclic AMP is found predominantly at the basal and lateral sides of brush border cells and in the lamina propria, while cyclic GMP is located to the brush border membrane, smooth muscle, and nuclear elements. In testis, cyclic AMP is found in cytoplasm of cells at the perimeter of the seminiferrous tubules and in interstitial cells, while cyclic AMP is visualized on the plasma membrane of the cells lining the tubules. Cyclic GMP is also seen on chromosomes of premeiotic spermatocytes and in sperm. These data provide histological evidence implicating diverse roles for the nucleotides in these tissues. The nuclear localization of cyclic GMP in all of these tissues suggests a role for the nucleotide in nucleus-directed events.", "contents": "Immunohistochemical localization of 3': 5'-cyclic AMP and 3': 5'-cyclic GMP in rat liver, intestine, and testis. Cyclic GMP and cyclic AMP have been localized in rat liver, small intestine, and testis by a fluorescent immunocytochemical procedure. In liver, cyclic AMP is distributed along sinusoids predominantly, and increased fluorescence is seen sinusoidal areas after glucagon administration. Cyclic GMP is located in nuclear elements and on the plasma membranes of hepatocytes. In jejunum, cyclic AMP is found predominantly at the basal and lateral sides of brush border cells and in the lamina propria, while cyclic GMP is located to the brush border membrane, smooth muscle, and nuclear elements. In testis, cyclic AMP is found in cytoplasm of cells at the perimeter of the seminiferrous tubules and in interstitial cells, while cyclic AMP is visualized on the plasma membrane of the cells lining the tubules. Cyclic GMP is also seen on chromosomes of premeiotic spermatocytes and in sperm. These data provide histological evidence implicating diverse roles for the nucleotides in these tissues. The nuclear localization of cyclic GMP in all of these tissues suggests a role for the nucleotide in nucleus-directed events."} {"id": "PMID:166377", "title": "Properties of cytoplasmic mutants of Saccharomyces cerevisiae with specific lesions in cytochrome oxidase.", "content": "Two mutants with specific defects in cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) have been isolated from cultures of Saccharomyces cerevisiae exposed to the mutagens ethyl-methane sulfonate and Mn++. The mutations have been shown to be extranuclear by two criteria. The phenotype persists in diploids formed by a cross with a p-o strain of yeast of the opposite mating type. Tetrad analysis indicates a non-Mendelian segregation (4:0 and 0:4) of the mutations. Both mutants show a total absence of cytochrome oxidase activity and of spectral cytochromes a and as. One of the mutants has been shown to be missing a polypeptide synthesized by mitochondria. The migration of this protein on polyacrylamide gels corresponds to the highest-molecular-weight subunit of cytochrome oxidase.", "contents": "Properties of cytoplasmic mutants of Saccharomyces cerevisiae with specific lesions in cytochrome oxidase. Two mutants with specific defects in cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) have been isolated from cultures of Saccharomyces cerevisiae exposed to the mutagens ethyl-methane sulfonate and Mn++. The mutations have been shown to be extranuclear by two criteria. The phenotype persists in diploids formed by a cross with a p-o strain of yeast of the opposite mating type. Tetrad analysis indicates a non-Mendelian segregation (4:0 and 0:4) of the mutations. Both mutants show a total absence of cytochrome oxidase activity and of spectral cytochromes a and as. One of the mutants has been shown to be missing a polypeptide synthesized by mitochondria. The migration of this protein on polyacrylamide gels corresponds to the highest-molecular-weight subunit of cytochrome oxidase."} {"id": "PMID:166374", "title": "[The effect of STH, TTH and ACTH on several aspects of copper, sodium and potassium metabolism in the livers of hypophysectomized white rats].", "content": "It was found in experiments on male albino rats that hypophysectomy was accompanied by an increase of potassium (on account of its accumulation in the mitochondria, nuclei and the microsomes) and copper in the liver. At the same time there was an increase in this organ of tha activity of Mg-2+-Na-+-K-+-ATPase and Mg-+-ATPase, and also a rise of ceruloplasmin activity in the blood serum. STH and TTH restored the sodium content to the normal and increased potassium level in the liver of hypophysectomized rats. ACTH and STH increased copper content in the hepatic tissue and normalized the activity of ceruloplasmin in the blood. All the hormones used promoted normalization of ATP-ase activity.", "contents": "[The effect of STH, TTH and ACTH on several aspects of copper, sodium and potassium metabolism in the livers of hypophysectomized white rats]. It was found in experiments on male albino rats that hypophysectomy was accompanied by an increase of potassium (on account of its accumulation in the mitochondria, nuclei and the microsomes) and copper in the liver. At the same time there was an increase in this organ of tha activity of Mg-2+-Na-+-K-+-ATPase and Mg-+-ATPase, and also a rise of ceruloplasmin activity in the blood serum. STH and TTH restored the sodium content to the normal and increased potassium level in the liver of hypophysectomized rats. ACTH and STH increased copper content in the hepatic tissue and normalized the activity of ceruloplasmin in the blood. All the hormones used promoted normalization of ATP-ase activity."} {"id": "PMID:166378", "title": "Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro.", "content": "NAD is a necessary cofactor for the activation of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by cholera toxin. Lysates of certain types of cell that hydrolyze their endogenous store of NAD after cell disruption respond poorly or not at all to cholera toxin. Lysates of pigeon erythrocytes, which lack enzymes that degrade NAD, provide a convenient and reproducible system for assaying the activity of cholera toxin in vitro and allow investigation of the mechanism of action of the toxin upon broken cells.", "contents": "Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro. NAD is a necessary cofactor for the activation of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by cholera toxin. Lysates of certain types of cell that hydrolyze their endogenous store of NAD after cell disruption respond poorly or not at all to cholera toxin. Lysates of pigeon erythrocytes, which lack enzymes that degrade NAD, provide a convenient and reproducible system for assaying the activity of cholera toxin in vitro and allow investigation of the mechanism of action of the toxin upon broken cells."} {"id": "PMID:166379", "title": "Beta-adrenergic stimulation of pineal N-acetyltransferase: adenosine 3':5'-cyclic monophosphate stimulates both RNA and protein synthesis.", "content": "The lag period in the induction of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase EC 2.3.1.5) by catecholamines via the beta-adrenergic receptor varies with the length of exposure of the rat to light or darkness. If rats have been exposed to light and reduced sympathetic nerve activity for more than 12 hr, this lag period is 1-2 hr long. Under these conditions, actinomycin D completely blocks the induction of N-acetyltransferase by isoproterenol and by dibutyryl adenosine 3':5'-cyclic monophosphate (cyclic AMP). In contrast, if enzyme activity is caused to fall by brief exposure to light at night when N-acetyltransferase activity is high, reinduction by catecholamines occurs almost immediately. In this case, actinomycin D does not block the reinduction of N-acetyltransferase by isoproterenol or by dibutyryl cyclic AMP. Cycloheximide blocks N-acetyltransferase induction under all conditions tested. Thus, new protein synthesis is always required for N-acetyltransferase induction; however, the requirement for RNA synthesis is variable, and contributes to the length of the lag period for induction. It is postulated that both beta-adrenergic stimulation and dibutyryl cyclic AMP act intracellularly at two separate sites in the induction of pineal N-acetyltransferase. One site is in the stimulation of transcription, and the other is in the stimulation of post-transcriptional events.", "contents": "Beta-adrenergic stimulation of pineal N-acetyltransferase: adenosine 3':5'-cyclic monophosphate stimulates both RNA and protein synthesis. The lag period in the induction of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase EC 2.3.1.5) by catecholamines via the beta-adrenergic receptor varies with the length of exposure of the rat to light or darkness. If rats have been exposed to light and reduced sympathetic nerve activity for more than 12 hr, this lag period is 1-2 hr long. Under these conditions, actinomycin D completely blocks the induction of N-acetyltransferase by isoproterenol and by dibutyryl adenosine 3':5'-cyclic monophosphate (cyclic AMP). In contrast, if enzyme activity is caused to fall by brief exposure to light at night when N-acetyltransferase activity is high, reinduction by catecholamines occurs almost immediately. In this case, actinomycin D does not block the reinduction of N-acetyltransferase by isoproterenol or by dibutyryl cyclic AMP. Cycloheximide blocks N-acetyltransferase induction under all conditions tested. Thus, new protein synthesis is always required for N-acetyltransferase induction; however, the requirement for RNA synthesis is variable, and contributes to the length of the lag period for induction. It is postulated that both beta-adrenergic stimulation and dibutyryl cyclic AMP act intracellularly at two separate sites in the induction of pineal N-acetyltransferase. One site is in the stimulation of transcription, and the other is in the stimulation of post-transcriptional events."} {"id": "PMID:166380", "title": "Isolation of a glycogen synthase I kinase that is independent of adenosine 3':5'-monophosphate.", "content": "Three protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) were detected when the soluble fraction of rabbit kidney medulla was chromatographed on DEAE-cellulose with a linear NaC1 gradient. The first two kinases eluted (Peak 1 and Peak II) were cyclic-AMP-dependent, wheras Peak III was cyclic-AMP-independent. A procedure was developed to separate the catalytic subunit of Peak II cyclic-AMP-dependent protein kinase (representing the bulk of the histone kinase activity) from Peak III protein kinase. In contrast to the catalytic subunit, Peak III protein kinase phosphorylated casein more rapidly than histone. Peak III was insensitive to the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinases and appeared to have a higher requirement for ATP than did the catalytic subunit. Peak III catalyzed the conversion of glycogen synthase (UDPglucose:glycogen alpha-4-glucosyltransferase, EC 2.4.1.11) from the I (glucose-6-phosphate-independent) to the D (glucose-6-phosphate-dependent) form. This conversion was dependent on Mg-2+ and ATP and was unaffected by cyclic AMP, cyclic GMP, or the protein inhibitor. Glycogen synthase I in the soluble fraction of kidney medulla could be converted to the D form by endogenous glycogen synthase I kinase if Mg-2+ and ATP were added. Most of this glycogen synthase I kinase activity was unaffected by cyclic AMP or by the protein inhibitor, suggesting that Peak III may be of major importance in the regulation of glycogen synthase in vivo.", "contents": "Isolation of a glycogen synthase I kinase that is independent of adenosine 3':5'-monophosphate. Three protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) were detected when the soluble fraction of rabbit kidney medulla was chromatographed on DEAE-cellulose with a linear NaC1 gradient. The first two kinases eluted (Peak 1 and Peak II) were cyclic-AMP-dependent, wheras Peak III was cyclic-AMP-independent. A procedure was developed to separate the catalytic subunit of Peak II cyclic-AMP-dependent protein kinase (representing the bulk of the histone kinase activity) from Peak III protein kinase. In contrast to the catalytic subunit, Peak III protein kinase phosphorylated casein more rapidly than histone. Peak III was insensitive to the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinases and appeared to have a higher requirement for ATP than did the catalytic subunit. Peak III catalyzed the conversion of glycogen synthase (UDPglucose:glycogen alpha-4-glucosyltransferase, EC 2.4.1.11) from the I (glucose-6-phosphate-independent) to the D (glucose-6-phosphate-dependent) form. This conversion was dependent on Mg-2+ and ATP and was unaffected by cyclic AMP, cyclic GMP, or the protein inhibitor. Glycogen synthase I in the soluble fraction of kidney medulla could be converted to the D form by endogenous glycogen synthase I kinase if Mg-2+ and ATP were added. Most of this glycogen synthase I kinase activity was unaffected by cyclic AMP or by the protein inhibitor, suggesting that Peak III may be of major importance in the regulation of glycogen synthase in vivo."} {"id": "PMID:166381", "title": "Changes in relative levels of guanosine-3':5'-monophosphate-dependent and adenosine-3':5'-monophosphate-dependent protein kinases in lung, heart, and brain of developing guinea pigs.", "content": "Canges in relative levels of protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) stimulated by either guanosine 3':5'-monophosphate (cyclic-GMP) or adenosine 3':5'-monophosphate (cyclic-AMP) were examined in extracts of the lung, heart, brain, and liver from guinea pigs at various stages of development. The level of cyclic-GMP-dependent protein kinase in the fetal lung, which was found to be the highest of any mammalian tissue samples examined, declined during development. On the other hand, the level of cyclic-AMP-dependent protein kinase in the same extracts, which was initially lower than that of the cyclic-GMP-dependent enzyme, increased during development and reached a level higher than that of the cyclic-GMP-dependent enzyme when the animals reached maturity. This reciprocal change in level of the two classes of protein kinases in developing lung was demonstrated further by chromatographing the extracts on Sephadex G-200 and quantitating the activity of the isolated enzymes. A decrease in the ratio of the two classes of protein kinases qualitatively similar to that seen in the lung was also noted in the developing heart. An increase in the ratio of the enzymes, however, was seen in the developing brain. Unlike in the lung, heart, and brain, no change in relative level and ratio of the enzymes was noted in liver during development. These results suggest that a balance between the effects of cyclic-GMP-dependent and cyclic-AMP-dependent protein kinases may be important in normal development of certain tissues.", "contents": "Changes in relative levels of guanosine-3':5'-monophosphate-dependent and adenosine-3':5'-monophosphate-dependent protein kinases in lung, heart, and brain of developing guinea pigs. Canges in relative levels of protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) stimulated by either guanosine 3':5'-monophosphate (cyclic-GMP) or adenosine 3':5'-monophosphate (cyclic-AMP) were examined in extracts of the lung, heart, brain, and liver from guinea pigs at various stages of development. The level of cyclic-GMP-dependent protein kinase in the fetal lung, which was found to be the highest of any mammalian tissue samples examined, declined during development. On the other hand, the level of cyclic-AMP-dependent protein kinase in the same extracts, which was initially lower than that of the cyclic-GMP-dependent enzyme, increased during development and reached a level higher than that of the cyclic-GMP-dependent enzyme when the animals reached maturity. This reciprocal change in level of the two classes of protein kinases in developing lung was demonstrated further by chromatographing the extracts on Sephadex G-200 and quantitating the activity of the isolated enzymes. A decrease in the ratio of the two classes of protein kinases qualitatively similar to that seen in the lung was also noted in the developing heart. An increase in the ratio of the enzymes, however, was seen in the developing brain. Unlike in the lung, heart, and brain, no change in relative level and ratio of the enzymes was noted in liver during development. These results suggest that a balance between the effects of cyclic-GMP-dependent and cyclic-AMP-dependent protein kinases may be important in normal development of certain tissues."} {"id": "PMID:166382", "title": "Neutron scattering study of human serum low density lipoprotein.", "content": "Regions of different proton density in the low density lipoprotein (LDL) particle from human serum have been determined by neutron scattering. From measurements in various H2O/D2O mixtures, the LDL particle appears to be quasi-spherical, with the centers of gravity of the hydrocarbon and polar regions coinciding. The average volume occupied by a particle was found to be 3.2 X 10-6 A-3, with the volume fraction occupied by the hydrocarbons being 60%. The ratius of gyration of the hydrocarbon region was 64 A, while that of the polar region was 100 A. consequently, the core of LDL is predominantly occupied by the hydrocarbon chains, while the outer shell is sparsely occupied by protein emerging from the lipid core.", "contents": "Neutron scattering study of human serum low density lipoprotein. Regions of different proton density in the low density lipoprotein (LDL) particle from human serum have been determined by neutron scattering. From measurements in various H2O/D2O mixtures, the LDL particle appears to be quasi-spherical, with the centers of gravity of the hydrocarbon and polar regions coinciding. The average volume occupied by a particle was found to be 3.2 X 10-6 A-3, with the volume fraction occupied by the hydrocarbons being 60%. The ratius of gyration of the hydrocarbon region was 64 A, while that of the polar region was 100 A. consequently, the core of LDL is predominantly occupied by the hydrocarbon chains, while the outer shell is sparsely occupied by protein emerging from the lipid core."} {"id": "PMID:166383", "title": "NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin,.", "content": "Pseudomonas aeruginosa toxin (PA toxin) inhibits protein synthesis in a reticulocyte cell-free system. The inhibition requires NAD and results in a block at an elongation step of polypeptide assembly. PA toxin was found to act like diphtheria toxin fragment A. Both toxins catalyze the transfer of radioactivity from nicotinamide(U-14-C)adenine dinucleotide ((14-C)NAD) into covalent linkage with the 100,000 dalton elongation (EF-2) protein. Furthermore, in the presence of a limiting amount of EF-2, excess toxin, and (14-C)NAD, the two toxins were non-additive in the amount of label transferred to EF-3. Unlike free fragment A of diphtheria toxin, the enzymatic activity of PA toxin is heat labile and neutralizable with antibody to PA toxin but not with antibody to fragment A. Although PA and diphtheria toxins have different cellular specificities and molecular properties and produce different clinical symptoms, their intracellular mechanisms of action appear to be identical.", "contents": "NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin,. Pseudomonas aeruginosa toxin (PA toxin) inhibits protein synthesis in a reticulocyte cell-free system. The inhibition requires NAD and results in a block at an elongation step of polypeptide assembly. PA toxin was found to act like diphtheria toxin fragment A. Both toxins catalyze the transfer of radioactivity from nicotinamide(U-14-C)adenine dinucleotide ((14-C)NAD) into covalent linkage with the 100,000 dalton elongation (EF-2) protein. Furthermore, in the presence of a limiting amount of EF-2, excess toxin, and (14-C)NAD, the two toxins were non-additive in the amount of label transferred to EF-3. Unlike free fragment A of diphtheria toxin, the enzymatic activity of PA toxin is heat labile and neutralizable with antibody to PA toxin but not with antibody to fragment A. Although PA and diphtheria toxins have different cellular specificities and molecular properties and produce different clinical symptoms, their intracellular mechanisms of action appear to be identical."} {"id": "PMID:166384", "title": "Adenosine 3':5'-cyclic monophosphate as mediator of catabolite repression in Escherichia coli.", "content": "Measurements of intracellular adenosine 3':5'-cyclic monophosphate (cAMP) concentrations in E. coli under a variety of conditions show that levels of this nucleotide are well correlated with the rate of synthesis of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in both catabolite repression and transient repression. These results, combined with extensive genetic and in vitro studies from a number of laboratories on the role of cAMP in E. coli, provide strong support for the concept that intracellular cAMP levels mediate the effects of catabolite and transient repression on rates on enzyme synthesis. Under all conditions studied, excretion can be described by a single rate constant, 2.1 min-1 at 37 degrees, indicating that intracellular levels cannot be regulated by alterations in the rate of cAMP excretion. Our data are fully consistent with the idea that carbon sources control intracellular cAMP levels by effects on its synthesis.", "contents": "Adenosine 3':5'-cyclic monophosphate as mediator of catabolite repression in Escherichia coli. Measurements of intracellular adenosine 3':5'-cyclic monophosphate (cAMP) concentrations in E. coli under a variety of conditions show that levels of this nucleotide are well correlated with the rate of synthesis of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in both catabolite repression and transient repression. These results, combined with extensive genetic and in vitro studies from a number of laboratories on the role of cAMP in E. coli, provide strong support for the concept that intracellular cAMP levels mediate the effects of catabolite and transient repression on rates on enzyme synthesis. Under all conditions studied, excretion can be described by a single rate constant, 2.1 min-1 at 37 degrees, indicating that intracellular levels cannot be regulated by alterations in the rate of cAMP excretion. Our data are fully consistent with the idea that carbon sources control intracellular cAMP levels by effects on its synthesis."} {"id": "PMID:166385", "title": "Antigen-stimulated changes in cyclic nucleotide levels in the mouse.", "content": "Mice injected intravenously with sheep erythrocytes (sRBC) demonstrate a transient increase in splenic cAMP levels (4-fold), which peak at 2 min after injection and return to basal levels by 20 min. In addition to the change in cAMP, an increase in splenic cGMP levels (1.5-fold) occurs beginning 5-10 min after sRBC injection, and persists for up to 7 days. During this period cAMP levels remain at or below control levels in the spleen. There is no change in 3':5' cyclic nucleotide levels in the liver and a small increase (1.2- to 1.3-fold) in the thymus at the time when splenic cyclic nucleotide levels are elevated. The changes in splenic cyclic nucleotide levels appear to be dependent on the presence of thymus-derived (T) lymphocytes, since little change occurs in cAMP and changes in cGMP are absent in athymic nude mice. In addition, cAMP levels were increased by pretreatment of normal mice with cortisone acetate, which selects for mature T lymphocytes. Agents that block autonomic nervous system functions have no effect on the early sRBC-induced changes in cyclic nucleotide levels.Indomethacin, an inhibitor of prostaglandin synthesis, reduces the change in cAMP level by 50% and blocks the change in cGMP levels completely. Secondary stimulation with sRBC results in a larger increase in cAMP levels than that seen with a primary injection of sRBC, indicating the presence of specific antigen-sensitive memory cells. Changes in splenic cyclic nucleotide levels cannot be detected at early times after the injection of soluble protein antigens such as bovine serum albumin and keyhole limpet hemocyanin. Salmonella H antigen stimulates a 2-fold increase in cAMP levels, the increase occurring more slowly than with sRBC. The in vivo changes incyclic nucleotide levels are correlated with known changes in cyclic nucleotide levels which have been documented in vitro in both T-cells and T-cell-dependent-B-cell (bone-marrow derived) antibody responses.", "contents": "Antigen-stimulated changes in cyclic nucleotide levels in the mouse. Mice injected intravenously with sheep erythrocytes (sRBC) demonstrate a transient increase in splenic cAMP levels (4-fold), which peak at 2 min after injection and return to basal levels by 20 min. In addition to the change in cAMP, an increase in splenic cGMP levels (1.5-fold) occurs beginning 5-10 min after sRBC injection, and persists for up to 7 days. During this period cAMP levels remain at or below control levels in the spleen. There is no change in 3':5' cyclic nucleotide levels in the liver and a small increase (1.2- to 1.3-fold) in the thymus at the time when splenic cyclic nucleotide levels are elevated. The changes in splenic cyclic nucleotide levels appear to be dependent on the presence of thymus-derived (T) lymphocytes, since little change occurs in cAMP and changes in cGMP are absent in athymic nude mice. In addition, cAMP levels were increased by pretreatment of normal mice with cortisone acetate, which selects for mature T lymphocytes. Agents that block autonomic nervous system functions have no effect on the early sRBC-induced changes in cyclic nucleotide levels.Indomethacin, an inhibitor of prostaglandin synthesis, reduces the change in cAMP level by 50% and blocks the change in cGMP levels completely. Secondary stimulation with sRBC results in a larger increase in cAMP levels than that seen with a primary injection of sRBC, indicating the presence of specific antigen-sensitive memory cells. Changes in splenic cyclic nucleotide levels cannot be detected at early times after the injection of soluble protein antigens such as bovine serum albumin and keyhole limpet hemocyanin. Salmonella H antigen stimulates a 2-fold increase in cAMP levels, the increase occurring more slowly than with sRBC. The in vivo changes incyclic nucleotide levels are correlated with known changes in cyclic nucleotide levels which have been documented in vitro in both T-cells and T-cell-dependent-B-cell (bone-marrow derived) antibody responses."} {"id": "PMID:166386", "title": "A genetic determinant of the phenotypic variance of the molecular weight of low density lipoprotein.", "content": "The molecular weight of monodisperse human plasma low densitylipoprotein has been measured in 69 individuals and found to vary over the range of 2.4 to 3.9 X 10-6. By contrast, the molecular weight of low density lipoprotein measured on two separate occasions for specific individuals shows a mean difference of 0.07 X 10-6 and a standard deviation of 0.08 X 10-6; hence low density lipoprotein differing in molecular weight by greater than 0.2 X 10-6 may be considered different macomolecules. The distribution of the molecular weight of low density lipoprotein does not differ as a function of age or sex. Hyperlipemic subjects having monodisperse low density lipoprotein show similar molecular weight distribution to normal subjects, as do subjects with premature coronary artery disease. Family studies reveal a correlation coefficient of 0.82 between average molecular weights of parents and offspring, with significance at 0.01. In order to assess the influence of environment on molecular weight of low density lipoprotein, the correlation coefficient between the fathers' and mothers' low density lipoprotein was measured and no statistically significant correlation was found. These data are interpreted as strong evidence for a genetic determination of molecular weight of low density lipoprotein. A study of individuals in five families yields molecular weight data consistent with a single gene locus genetic mode of inheritance without dominance. The regression coefficient of the mean low denisty lipoprotein parental molecular weight on the offspring molecular weight is 0.30. If the variability of molecular weight is considered as an expression of phenotypic variance, then the regression analysis identified 30% of this phenotypic variance as arising from additive gene action presumably at a single locus. Segregation in the family data is consistent. Since the differences in molecular weight of low density lipoprotein arise from differences in the amount of lipid bound to the apoprotein, it is likely that an additional portion of the phenotypic variance of the molecular weight results from individual variations in the metabolism of low density lipoprotein, which yield differences in lipid content. The individual variation in molecular weight is only approximately 5%; hence those metabolic sequences that influence molecular weight of low density lipoproteins must be precisely controlled.", "contents": "A genetic determinant of the phenotypic variance of the molecular weight of low density lipoprotein. The molecular weight of monodisperse human plasma low densitylipoprotein has been measured in 69 individuals and found to vary over the range of 2.4 to 3.9 X 10-6. By contrast, the molecular weight of low density lipoprotein measured on two separate occasions for specific individuals shows a mean difference of 0.07 X 10-6 and a standard deviation of 0.08 X 10-6; hence low density lipoprotein differing in molecular weight by greater than 0.2 X 10-6 may be considered different macomolecules. The distribution of the molecular weight of low density lipoprotein does not differ as a function of age or sex. Hyperlipemic subjects having monodisperse low density lipoprotein show similar molecular weight distribution to normal subjects, as do subjects with premature coronary artery disease. Family studies reveal a correlation coefficient of 0.82 between average molecular weights of parents and offspring, with significance at 0.01. In order to assess the influence of environment on molecular weight of low density lipoprotein, the correlation coefficient between the fathers' and mothers' low density lipoprotein was measured and no statistically significant correlation was found. These data are interpreted as strong evidence for a genetic determination of molecular weight of low density lipoprotein. A study of individuals in five families yields molecular weight data consistent with a single gene locus genetic mode of inheritance without dominance. The regression coefficient of the mean low denisty lipoprotein parental molecular weight on the offspring molecular weight is 0.30. If the variability of molecular weight is considered as an expression of phenotypic variance, then the regression analysis identified 30% of this phenotypic variance as arising from additive gene action presumably at a single locus. Segregation in the family data is consistent. Since the differences in molecular weight of low density lipoprotein arise from differences in the amount of lipid bound to the apoprotein, it is likely that an additional portion of the phenotypic variance of the molecular weight results from individual variations in the metabolism of low density lipoprotein, which yield differences in lipid content. The individual variation in molecular weight is only approximately 5%; hence those metabolic sequences that influence molecular weight of low density lipoproteins must be precisely controlled."} {"id": "PMID:166387", "title": "Viral and cellular DNA synthesis in nuclei from human lymphocytes transformed by Epstein-Barr virus.", "content": "A DNA-synthesizing system in vitro, using nuclei prepared by treatment of human lymphocytes with the detergent Brij 58, was developed. Nuclei from cultured lymphocytes synthesized DNA for as long as 5 hr, and required ATP, deoxynucleoside triphosphates, magnesium, and a calcium chelator. In nuclei from a partially synchronized line of cultured lymphocytes carrying several hundred copies of the Epstein-Barr viral genome, synthesis in vitro was predominately viral in early S phase and cellular in late S phase. These and other data suggested that the DNA synthesis observed in vitro was predominately replicative.", "contents": "Viral and cellular DNA synthesis in nuclei from human lymphocytes transformed by Epstein-Barr virus. A DNA-synthesizing system in vitro, using nuclei prepared by treatment of human lymphocytes with the detergent Brij 58, was developed. Nuclei from cultured lymphocytes synthesized DNA for as long as 5 hr, and required ATP, deoxynucleoside triphosphates, magnesium, and a calcium chelator. In nuclei from a partially synchronized line of cultured lymphocytes carrying several hundred copies of the Epstein-Barr viral genome, synthesis in vitro was predominately viral in early S phase and cellular in late S phase. These and other data suggested that the DNA synthesis observed in vitro was predominately replicative."} {"id": "PMID:166388", "title": "Coenzyme A requirement of malaria parasites: enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae.", "content": "Normal duck erythrocytes and erythrocytes infected with Plasmodium lopharae have all of the enzymes for coenzyme A biosynthesis, whereas parasites freed from their host cells have non. Since erythrocytefree cultivation of P. lophurae requires an exogenous source of coenzyme A, this parasite must obtain its coenzyme A entirely from the host cell during infection.", "contents": "Coenzyme A requirement of malaria parasites: enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae. Normal duck erythrocytes and erythrocytes infected with Plasmodium lopharae have all of the enzymes for coenzyme A biosynthesis, whereas parasites freed from their host cells have non. Since erythrocytefree cultivation of P. lophurae requires an exogenous source of coenzyme A, this parasite must obtain its coenzyme A entirely from the host cell during infection."} {"id": "PMID:166402", "title": "The relationship of small limb movements during REM sleep to dreamed limb action.", "content": "Ten adult subjects, selected for good dream recall and ability to produce spontaneously fine limb movements in the laboratory, reported their last dream experience after awakenings from REM sleep during various limb movement and no movement conditions. The reports were rated for amount and girdle location of dreamed actions by judges blind to the awakening condition. There was a significant correlation between the number of girdles moving before awakening and the amount of dreamed action. Also, when dreams from single girdle movement awakening conditions were examined, the girdle active before awakening was dreamed as moving to a significant degree.", "contents": "The relationship of small limb movements during REM sleep to dreamed limb action. Ten adult subjects, selected for good dream recall and ability to produce spontaneously fine limb movements in the laboratory, reported their last dream experience after awakenings from REM sleep during various limb movement and no movement conditions. The reports were rated for amount and girdle location of dreamed actions by judges blind to the awakening condition. There was a significant correlation between the number of girdles moving before awakening and the amount of dreamed action. Also, when dreams from single girdle movement awakening conditions were examined, the girdle active before awakening was dreamed as moving to a significant degree."} {"id": "PMID:166409", "title": "The air bronchogram in interstitial disease of the lungs. A radiological-pathological correlation.", "content": "The air bronchogram classically signals an end-air-space or \"alveolar\" filling process such as alveolar proteinosis and bronchioloalveolar-cell carcinoma. However, it can also occur in interstitial diseases, possibly leading to compressive atelectasis and causing crowding of tissue around open airways. In addition, such disease processes may encroach on distal airways, producing obstructive pneumonia which may then surround open proximal airways, as in sarcoidosis and lymphoma. In mixed \"alveolar\" and interstitial processes such as Pneumocystis carinii pneumonia and the late stages of hemosiderosis, \"alveolar\" filling may mask the interstitial disease.", "contents": "The air bronchogram in interstitial disease of the lungs. A radiological-pathological correlation. The air bronchogram classically signals an end-air-space or \"alveolar\" filling process such as alveolar proteinosis and bronchioloalveolar-cell carcinoma. However, it can also occur in interstitial diseases, possibly leading to compressive atelectasis and causing crowding of tissue around open airways. In addition, such disease processes may encroach on distal airways, producing obstructive pneumonia which may then surround open proximal airways, as in sarcoidosis and lymphoma. In mixed \"alveolar\" and interstitial processes such as Pneumocystis carinii pneumonia and the late stages of hemosiderosis, \"alveolar\" filling may mask the interstitial disease."} {"id": "PMID:166410", "title": "A new method of diagnosing myocardial contusion in man by radionuclide imaging.", "content": "A new method of diagnosing myocardial contusion was studied in 8 patients in whom the injured mycardium was visualized as an abnormal area of increased activity in the region of the heart one hour after intravenous injection of 10 mCi of 99m-Tc-Sn-polyphosphate or pyrophosphate. Serum enzymes in these patients were elevated, but electrocardiograms were nonspecific for myocardial injury. It is hoped that this new technique of imaging the injured myocardium will provide specific and confirmatory diagnosis of myocardial contusion associated with closed chest injuries.", "contents": "A new method of diagnosing myocardial contusion in man by radionuclide imaging. A new method of diagnosing myocardial contusion was studied in 8 patients in whom the injured mycardium was visualized as an abnormal area of increased activity in the region of the heart one hour after intravenous injection of 10 mCi of 99m-Tc-Sn-polyphosphate or pyrophosphate. Serum enzymes in these patients were elevated, but electrocardiograms were nonspecific for myocardial injury. It is hoped that this new technique of imaging the injured myocardium will provide specific and confirmatory diagnosis of myocardial contusion associated with closed chest injuries."} {"id": "PMID:166412", "title": "Total-lung irradiation in the treatment of pulmonary metastases.", "content": "Sixty-two patients with pulmonary metastases from a variety of primary malignant neoplasms were treated with total-lung irradiation. The incidence of radiation pneumonitis was 21%(13/62) overall, rising to 23% (9/39) in those receiving a tumor dose of 1,500 rads or more. Nine patients with radiation pneumonitis were given chemotherapy (actinomycin D) together with irradiation, and in this group the incidence of radiation pneumonitis was 25%. Five survivors, including 4 treated for metastatic Wilms' tumor, were treated more than 13 months prior to analysis without evidence of disease thus far. Total-lung irradiation for primary malignant neoplasms other than Wilms' tumor does not presently appear to be indicated. A dose of 1,500 rads in 2 weeks in conjunction with actinomycin D is recommended for metastatic Wilms' tumor.", "contents": "Total-lung irradiation in the treatment of pulmonary metastases. Sixty-two patients with pulmonary metastases from a variety of primary malignant neoplasms were treated with total-lung irradiation. The incidence of radiation pneumonitis was 21%(13/62) overall, rising to 23% (9/39) in those receiving a tumor dose of 1,500 rads or more. Nine patients with radiation pneumonitis were given chemotherapy (actinomycin D) together with irradiation, and in this group the incidence of radiation pneumonitis was 25%. Five survivors, including 4 treated for metastatic Wilms' tumor, were treated more than 13 months prior to analysis without evidence of disease thus far. Total-lung irradiation for primary malignant neoplasms other than Wilms' tumor does not presently appear to be indicated. A dose of 1,500 rads in 2 weeks in conjunction with actinomycin D is recommended for metastatic Wilms' tumor."} {"id": "PMID:166415", "title": "Ultrastructural changes accompanying mitosporogenesis in Ectocarpus parvus.", "content": "The plurilocular zoosporangium of Ectocarpus parvus Saunders in initiated as a uniseriate branch from a vegetative cell. Subsequent anticlinal and periclinal divisions of the cells leads to enlargement of the sporangium and the formation of multiple locules. Each locule containes a single biflagellate zoospore. Ultrastructural changes accompanying these events include a reduction in the size of chromatophores, a reduction in the number of dictyosomes and the appearance of plasmalemmasomes in later stages. Enlargement of the mitochondria and a decrease in size of the nucleus occur in the final stages of zoospore formation. Comparison with the vegetative and sporogenous cells of other brown algae are made.", "contents": "Ultrastructural changes accompanying mitosporogenesis in Ectocarpus parvus. The plurilocular zoosporangium of Ectocarpus parvus Saunders in initiated as a uniseriate branch from a vegetative cell. Subsequent anticlinal and periclinal divisions of the cells leads to enlargement of the sporangium and the formation of multiple locules. Each locule containes a single biflagellate zoospore. Ultrastructural changes accompanying these events include a reduction in the size of chromatophores, a reduction in the number of dictyosomes and the appearance of plasmalemmasomes in later stages. Enlargement of the mitochondria and a decrease in size of the nucleus occur in the final stages of zoospore formation. Comparison with the vegetative and sporogenous cells of other brown algae are made."} {"id": "PMID:166416", "title": "Evidence for a possible prostaglandin link in ACTH-induced steroidogenesis.", "content": "The steroidogenic response to ACTH prostaglandin E2 (PGE2) was studied in cat adrenocortical cells dispersed with trypsin. The dose-response curves of both agents were qualitatively and quantitatively similar. Exposure to PGE2 or ACTH in the presence of labeled steroid precursor (acetate) resulted in the accumulation of comparable levels of steroid intermediates and end-product. Submaximal or maximal concentrations of ACTH and PGE-2 given simultaneously elicited a response which was no greater than that obtained with either stimulant alone. Although calcium was required for optimal PGE-2 stimulation of steroid production, this requirement with ACTH as the stimulant, but greater than with butyryl cyclic AMP. PGE-2-induced increase in the adrenal cyclic AMP was not statistically significant and was small in relation to that found with equipotent steroidogenic ACTH concentrations. The possible relationship between prostaglandins, cyclic AMP, and calcium in the action of ACTH is discussed.", "contents": "Evidence for a possible prostaglandin link in ACTH-induced steroidogenesis. The steroidogenic response to ACTH prostaglandin E2 (PGE2) was studied in cat adrenocortical cells dispersed with trypsin. The dose-response curves of both agents were qualitatively and quantitatively similar. Exposure to PGE2 or ACTH in the presence of labeled steroid precursor (acetate) resulted in the accumulation of comparable levels of steroid intermediates and end-product. Submaximal or maximal concentrations of ACTH and PGE-2 given simultaneously elicited a response which was no greater than that obtained with either stimulant alone. Although calcium was required for optimal PGE-2 stimulation of steroid production, this requirement with ACTH as the stimulant, but greater than with butyryl cyclic AMP. PGE-2-induced increase in the adrenal cyclic AMP was not statistically significant and was small in relation to that found with equipotent steroidogenic ACTH concentrations. The possible relationship between prostaglandins, cyclic AMP, and calcium in the action of ACTH is discussed."} {"id": "PMID:166417", "title": "Action of luteinizing hormone-releasing hormone and synthesis of prostaglandin in the pituitary gland.", "content": "The possibility that prostaglandin E2 (PGE2) may play a role in luteinizing hormone (LH) release was examined using an in vitro model. Addition of luteinizing hormone-releasing hormone (LH-RH) to the culture medium stimulated cyclic AMP accumulation and LH-release by incubated hemipituitaries, but did not affect the level of PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 content in the pituitary, but did not impair the stimulatory action of LH-RH on either cyclic AMP accumulation or LH-release. Flufenamic acid on its own caused LH-release, but the drug abolished the effect of LH-RH on cyclic AMP accumulation. The mechanism of this action of flufenamic acid is not understood. It is concluded that the stimulatory action of LH-RH on pituitary cyclic AMP production and LH release is not mediated by prostaglandins.", "contents": "Action of luteinizing hormone-releasing hormone and synthesis of prostaglandin in the pituitary gland. The possibility that prostaglandin E2 (PGE2) may play a role in luteinizing hormone (LH) release was examined using an in vitro model. Addition of luteinizing hormone-releasing hormone (LH-RH) to the culture medium stimulated cyclic AMP accumulation and LH-release by incubated hemipituitaries, but did not affect the level of PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 content in the pituitary, but did not impair the stimulatory action of LH-RH on either cyclic AMP accumulation or LH-release. Flufenamic acid on its own caused LH-release, but the drug abolished the effect of LH-RH on cyclic AMP accumulation. The mechanism of this action of flufenamic acid is not understood. It is concluded that the stimulatory action of LH-RH on pituitary cyclic AMP production and LH release is not mediated by prostaglandins."} {"id": "PMID:166420", "title": "Inhibition of RNA-dependent DNA polymerase reaction by 6-(p-hydroxyphenylazo)-uracil: A result of drug induced dithiothreitol oxidation.", "content": "6-(P-hydroxyphenylazo)-uracil (HPUra) reduced by dithiothreitol inhibited AMV or RLV virion associated exogenous RNA-dependent DNA polymerase reactions. However, the inhibition was variable from experiment to experiment and was not consistent with the base specificity of HPUra seen for inhibition of gram positive DNA-dependent DNA polymerases. Increasing the concentration of dithiothreitol reversed the inhibition. Furthermore, at non-toxic concentrations, HPUra did not influence the plating efficiency of RLV in tissue culture, as measured by the ability to induce foci on sarcoma virus positive-leukemia virus negative cells. Oxidation of dithiothreitol in the presence or absence of HPUra was followed spectrophotometrically under enzyme conditions. HPUra catalyzed the oxidation of dithiothreitol under these conditions. Since dithiothreitol is required for optimum reaction rates, as well as complete disruption of virus in some polymerase assay systems, the oxidation of dithiothreitol in the presence of HPUra is sufficient to explain the inhibition seen.", "contents": "Inhibition of RNA-dependent DNA polymerase reaction by 6-(p-hydroxyphenylazo)-uracil: A result of drug induced dithiothreitol oxidation. 6-(P-hydroxyphenylazo)-uracil (HPUra) reduced by dithiothreitol inhibited AMV or RLV virion associated exogenous RNA-dependent DNA polymerase reactions. However, the inhibition was variable from experiment to experiment and was not consistent with the base specificity of HPUra seen for inhibition of gram positive DNA-dependent DNA polymerases. Increasing the concentration of dithiothreitol reversed the inhibition. Furthermore, at non-toxic concentrations, HPUra did not influence the plating efficiency of RLV in tissue culture, as measured by the ability to induce foci on sarcoma virus positive-leukemia virus negative cells. Oxidation of dithiothreitol in the presence or absence of HPUra was followed spectrophotometrically under enzyme conditions. HPUra catalyzed the oxidation of dithiothreitol under these conditions. Since dithiothreitol is required for optimum reaction rates, as well as complete disruption of virus in some polymerase assay systems, the oxidation of dithiothreitol in the presence of HPUra is sufficient to explain the inhibition seen."} {"id": "PMID:166421", "title": "Pseudorabies virus - induced neural hyperreactivity following occular and skin infections in the rat.", "content": "The types of functional disturbances caused by a neurotropic virus was investigated by means of neurophysiological techniques. Two types of neurophysiologic lesions were produced in the superior cervical sympathetic ganglia and sural nerve in rats infected with two distinct strains of pseudorabies virus. The pruritus-producing strain following intraocular inoculation displayed spontaneous activity in the ganglia both in vivo and in vitro. This activity was susceptible to the actions of ATP, AMP, pyridoxine, pyridoxamine, serotonin and gamma-aminobutyric acid (GABA). Following intradermal inoculation, spontaneous activity and pruritus were seen along the sural nerve. The non- pruritus producing strain caused meningoencephalitis with impaired sympathetic synaptic conduction. The relationship of these pathopharmacologic findings to pathogenesis of syndromes naturally or experimentally occurring in viral infection was assessed.", "contents": "Pseudorabies virus - induced neural hyperreactivity following occular and skin infections in the rat. The types of functional disturbances caused by a neurotropic virus was investigated by means of neurophysiological techniques. Two types of neurophysiologic lesions were produced in the superior cervical sympathetic ganglia and sural nerve in rats infected with two distinct strains of pseudorabies virus. The pruritus-producing strain following intraocular inoculation displayed spontaneous activity in the ganglia both in vivo and in vitro. This activity was susceptible to the actions of ATP, AMP, pyridoxine, pyridoxamine, serotonin and gamma-aminobutyric acid (GABA). Following intradermal inoculation, spontaneous activity and pruritus were seen along the sural nerve. The non- pruritus producing strain caused meningoencephalitis with impaired sympathetic synaptic conduction. The relationship of these pathopharmacologic findings to pathogenesis of syndromes naturally or experimentally occurring in viral infection was assessed."} {"id": "PMID:166422", "title": "Epstein-Barr virus: comparison of different strains for their biological activities in vitro.", "content": "Several sources of Epstein-Barr virus (EBV) were tested for the ability to superinfect Raji cells or to transform human cord blood leukocytes. EBV prepared from P3HR-1 cells showed only the ability to superinfect Raji cells whereas EBV from QIMR-WIL cells from a cell line (CRU-L1) derived from an infectious mononucleosis (IM) patient or virus from throat washings from IM patients transformed human cord blood leukocytes, but did not superinfect Raji cells.", "contents": "Epstein-Barr virus: comparison of different strains for their biological activities in vitro. Several sources of Epstein-Barr virus (EBV) were tested for the ability to superinfect Raji cells or to transform human cord blood leukocytes. EBV prepared from P3HR-1 cells showed only the ability to superinfect Raji cells whereas EBV from QIMR-WIL cells from a cell line (CRU-L1) derived from an infectious mononucleosis (IM) patient or virus from throat washings from IM patients transformed human cord blood leukocytes, but did not superinfect Raji cells."} {"id": "PMID:166423", "title": "Cellular cooperation in transformation by EB virus.", "content": "Human lymphoid cells transformed by Epstein-Barr (EB) virus are thought to be B-lymphocytes. Transformation of human mononuclear leukocytes by Epstein-Barr virus was decreased or lost by removing adhering or nonadhering mononuclear cells from the mixtures of peripheral blood leukocytes but was not decreased by removing T-lymphocytes. Recombining adherent and nonadherent mononuclear cells without T-lymphocytes restored transformability, but conditioned medium from cultures of adherent cells did not. Cooperation between non-adherent (B-cells) and adherent cells (monocytes) is necessary for EB virus transformation.", "contents": "Cellular cooperation in transformation by EB virus. Human lymphoid cells transformed by Epstein-Barr (EB) virus are thought to be B-lymphocytes. Transformation of human mononuclear leukocytes by Epstein-Barr virus was decreased or lost by removing adhering or nonadhering mononuclear cells from the mixtures of peripheral blood leukocytes but was not decreased by removing T-lymphocytes. Recombining adherent and nonadherent mononuclear cells without T-lymphocytes restored transformability, but conditioned medium from cultures of adherent cells did not. Cooperation between non-adherent (B-cells) and adherent cells (monocytes) is necessary for EB virus transformation."} {"id": "PMID:166432", "title": "Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization.", "content": "Mice were used to test the efficacy of active immunization in preventing latent infection of local sensory ganglia that follows inoculation of superficial epithelial surfaces with herpes simplex virus. Substantial but not complete protection was observed in animals immunized and challenged with herpes simplex virus type 1, but no protection was noted in animals immunized and challenged with herpes simplex virus type 2. Latent ganglionic infection can develop in immunized animals despite the presence of high titers of neutralizing antibody.", "contents": "Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization. Mice were used to test the efficacy of active immunization in preventing latent infection of local sensory ganglia that follows inoculation of superficial epithelial surfaces with herpes simplex virus. Substantial but not complete protection was observed in animals immunized and challenged with herpes simplex virus type 1, but no protection was noted in animals immunized and challenged with herpes simplex virus type 2. Latent ganglionic infection can develop in immunized animals despite the presence of high titers of neutralizing antibody."} {"id": "PMID:166433", "title": "Cell surface differences in ducts from cancerous and noncancerous human breasts.", "content": "The scanning electron microscope reveals structural differences between the apical microvilli of duct cells from cancerous and noncancerous human breasts. The alterations in the microvilli from carcinomatous breasts appear to be highly specific, to extend throughout the affected breast, and may be pathognomonic for this condition.", "contents": "Cell surface differences in ducts from cancerous and noncancerous human breasts. The scanning electron microscope reveals structural differences between the apical microvilli of duct cells from cancerous and noncancerous human breasts. The alterations in the microvilli from carcinomatous breasts appear to be highly specific, to extend throughout the affected breast, and may be pathognomonic for this condition."} {"id": "PMID:166434", "title": "Cell rigidity: Effect on concanavalin A-mediated agglutinability of fibroblasts after fixation.", "content": "A quantitative hemadsorption assay distinguishes the effects of membrane fixation on concanavalin A-mediated agglutinability of fixed cells with unfixed cells. We observed undiminished adherence of unfixed erythrocytes to glutaraldehyde-fixed normal and virus-transformed hamster fibroblasts coated with concanavalin A. Fixation of the erythrocytes abolished agglutination with fixed fibroblasts. The agglutinability of fixed cells is more likely related to increased cell rigidity than to decreased membrane fluidity.", "contents": "Cell rigidity: Effect on concanavalin A-mediated agglutinability of fibroblasts after fixation. A quantitative hemadsorption assay distinguishes the effects of membrane fixation on concanavalin A-mediated agglutinability of fixed cells with unfixed cells. We observed undiminished adherence of unfixed erythrocytes to glutaraldehyde-fixed normal and virus-transformed hamster fibroblasts coated with concanavalin A. Fixation of the erythrocytes abolished agglutination with fixed fibroblasts. The agglutinability of fixed cells is more likely related to increased cell rigidity than to decreased membrane fluidity."} {"id": "PMID:166435", "title": "Induced adhesion in Crassostrea virginica larvae.", "content": "Normal motile veliger larvae of the oyster, Crassostrea virginica, were observed swimming in pairs or trios. Adhesion between animals is firm and has a specific orientation. This adhesion can be induced in low frequencies by culturing larvae at high densities, and in much higher frequencies by inclusion of an antibiotic mix in the seawater culture medium.", "contents": "Induced adhesion in Crassostrea virginica larvae. Normal motile veliger larvae of the oyster, Crassostrea virginica, were observed swimming in pairs or trios. Adhesion between animals is firm and has a specific orientation. This adhesion can be induced in low frequencies by culturing larvae at high densities, and in much higher frequencies by inclusion of an antibiotic mix in the seawater culture medium."} {"id": "PMID:166436", "title": "[Anterior antehypaphyseal insufficiecency in the elderly].", "content": "The authors report 4 personal cases, and analyse 18 cases of anterior pituitary insufficiency in the elderly found in the world literature. The initial symptoms are not specific and are difficult to interpret. They are frequently attributed to physiological ageing. In the absence of early diagnois, the patient may become comatose, this coma is often irreversible in spite of hormone treatment. In 60% of cases, the cause of the pituitary failure was not found. In the onset of the latter, the role of ageing on pituitary function, the responsibility of circulatory failure between the hypothalamus and the pituitary and, finally, the existence of auto-immune mechanisms are then discussed.", "contents": "[Anterior antehypaphyseal insufficiecency in the elderly]. The authors report 4 personal cases, and analyse 18 cases of anterior pituitary insufficiency in the elderly found in the world literature. The initial symptoms are not specific and are difficult to interpret. They are frequently attributed to physiological ageing. In the absence of early diagnois, the patient may become comatose, this coma is often irreversible in spite of hormone treatment. In 60% of cases, the cause of the pituitary failure was not found. In the onset of the latter, the role of ageing on pituitary function, the responsibility of circulatory failure between the hypothalamus and the pituitary and, finally, the existence of auto-immune mechanisms are then discussed."} {"id": "PMID:166437", "title": "[Does rheumatic pleuresy exist?].", "content": "The authors report the case of a 20 year-old young man with old rheumatic heart disease in whom suddenly occurred sero-fibrinous pleurisy with fever. The usual cause of pleurisy, e.g. tuberculosis, were eliminated. On the other hadn, there was considerable evidence, including lengthening of the P-R interval, and raised anti-streptolysin titer at 1920 units, which suggested recurrence of rheumatic fever. The relationship between this disease and sero-fibrinous pleurisy is then discussed.", "contents": "[Does rheumatic pleuresy exist?]. The authors report the case of a 20 year-old young man with old rheumatic heart disease in whom suddenly occurred sero-fibrinous pleurisy with fever. The usual cause of pleurisy, e.g. tuberculosis, were eliminated. On the other hadn, there was considerable evidence, including lengthening of the P-R interval, and raised anti-streptolysin titer at 1920 units, which suggested recurrence of rheumatic fever. The relationship between this disease and sero-fibrinous pleurisy is then discussed."} {"id": "PMID:166438", "title": "[2 cases of hepatorenal polycystosis].", "content": "The authors report two cases of polycystic liver andkidney in two women. They were unusual in that the liver first gave risr to symptoms and the renal lesions were completely latent. Both hepatic and renal lesions were well tolerated in spite of hepatomegally. They emphasize the interest of laparoscopy and biopsy of the liver under direct vision, and selective aortography, in the diagnosis. They discuss the basic differences between polycystic liver and kidney in adults, from that in children ornewborn, and caroli's disease. Finally, they emphasize the usually poor prognosis dominated by progressive renal failure which should guide treatment. The latter depends on periodic supervision of the patient for the disease usually evolves slowly. Treatment should therefore be conservative. Tn some cases, however, renal transplantaton should be considered before irreversible renal failure in young subjects, at an age when it is still possible. On the other hand, the liver lesions do not require any radical treatment, unless there is intercurrent infection or pressure on neighbouringorgans.", "contents": "[2 cases of hepatorenal polycystosis]. The authors report two cases of polycystic liver andkidney in two women. They were unusual in that the liver first gave risr to symptoms and the renal lesions were completely latent. Both hepatic and renal lesions were well tolerated in spite of hepatomegally. They emphasize the interest of laparoscopy and biopsy of the liver under direct vision, and selective aortography, in the diagnosis. They discuss the basic differences between polycystic liver and kidney in adults, from that in children ornewborn, and caroli's disease. Finally, they emphasize the usually poor prognosis dominated by progressive renal failure which should guide treatment. The latter depends on periodic supervision of the patient for the disease usually evolves slowly. Treatment should therefore be conservative. Tn some cases, however, renal transplantaton should be considered before irreversible renal failure in young subjects, at an age when it is still possible. On the other hand, the liver lesions do not require any radical treatment, unless there is intercurrent infection or pressure on neighbouringorgans."} {"id": "PMID:166439", "title": "[Acute non-tuberculous military lung].", "content": "The authors report the case of a young woman with acute miliary appearance of the lung with asphyxia, from which she rapidly recovered. No cause was demonstrated; this illustrates the difficulty in diagnosis of this disease. Contact with a bird, led the authors to consider exogenous, allergic granulomatosis, but immunological examinations did not confirm this. Apart from tuberculosis, almost 50 different pathogenic organisms may cause acute respiratory failure associated with a miliary or reticulo-nodular appearance of the lung. The main methods of diagnosis are discussed in relation to the most commonly observed causes in France.", "contents": "[Acute non-tuberculous military lung]. The authors report the case of a young woman with acute miliary appearance of the lung with asphyxia, from which she rapidly recovered. No cause was demonstrated; this illustrates the difficulty in diagnosis of this disease. Contact with a bird, led the authors to consider exogenous, allergic granulomatosis, but immunological examinations did not confirm this. Apart from tuberculosis, almost 50 different pathogenic organisms may cause acute respiratory failure associated with a miliary or reticulo-nodular appearance of the lung. The main methods of diagnosis are discussed in relation to the most commonly observed causes in France."} {"id": "PMID:166440", "title": "[Neurologic complications of pagetic basilar impressions and their surgical treatment].", "content": "Paget's disease of the skull is the main cause of basilar artery syndromes in the adult. They may cause various neurological symptoms, including signs of ischemia of the spinal cord or medulla, or involvement of the cranial nerves and brain stem and, also, distant symptoms due to hydrocephalus, with various mental disorders including transient, recurrent, coma. The authors discuss 30 cases found in the world literature and 6 unreported personal cases, study the clinical symptoms of these cases of basilar artery compression due to Paget's disease, and the methods of neuro-radiological investigation, and emphasize the interest, in severe forms, of early surgical decompression before the stage of severe neurological complications. Regular supervision of patients with Pagets disease is thus essential to detect at an early stage, decompensation of basilar artery insufficiency in Paget's disease. In late forms, calcitonin may be indicated.", "contents": "[Neurologic complications of pagetic basilar impressions and their surgical treatment]. Paget's disease of the skull is the main cause of basilar artery syndromes in the adult. They may cause various neurological symptoms, including signs of ischemia of the spinal cord or medulla, or involvement of the cranial nerves and brain stem and, also, distant symptoms due to hydrocephalus, with various mental disorders including transient, recurrent, coma. The authors discuss 30 cases found in the world literature and 6 unreported personal cases, study the clinical symptoms of these cases of basilar artery compression due to Paget's disease, and the methods of neuro-radiological investigation, and emphasize the interest, in severe forms, of early surgical decompression before the stage of severe neurological complications. Regular supervision of patients with Pagets disease is thus essential to detect at an early stage, decompensation of basilar artery insufficiency in Paget's disease. In late forms, calcitonin may be indicated."} {"id": "PMID:166441", "title": "[Myeloma and osteocondensation (apropos of 2 cases)].", "content": "The authors report two cases of multiple myeloma which were typical both clinically and in the laboratory but XRay examination, on the other hand, showed appearances of osteocondensation. In the first case, XRay showed both lesions of osteolysis in the cranial vault and homogeneous condensation of D11 and L1, together with the left iliac crest. In the other case, there was osteolysis of the acetabulum together with areas of osteocondensation distributed throughout the pelvis and upper ends of the femurs, with two areas of annular fibrosis circumscribing the area of osteolysis, finally, homogeneous condensation of the skull. In both cases, bone biopsy confirmed the diagnosis of multiple myeloma showing both osteofibrosis and plasma cell infiltration of the bone marrow. This also permitted the authors to note the absence of any myelofibrosis or metamorphic neo-osteogenesis. Illustrated by these two cases, condensing multiple myeloma is a rare entity, the special clinical characteristics of which reside in its fairly frequent coexistence with peripheral neuritis which is probably similar to a para-neoplastic syndrome. The radiological appearances are mainly of four types: 1) Focal areas of bony condensation. 2) Areas of annular fibrosis circumscribing osteolysis. 3) Appearances of radial spicules, or 4) Osteocondensation extending to a fairly large part of the skeleton. The laboratory signs are identical with those in other types of multiple myeloma with a few exceptions, such as, rareness of hypercalcemia, more frequent tendency to hypocalcemia, rise in alkaline phosphatase, in a few cases. Bone biopsy confirms the diagnosis. The osteofibrosis resulted here from thickening of the osteoid seams by laying down of successive layers of bony substance, irregularly calcified and, also secondarily, metamorphic neo-osteogenesis in a few rare cases which also included myelofibrosis.", "contents": "[Myeloma and osteocondensation (apropos of 2 cases)]. The authors report two cases of multiple myeloma which were typical both clinically and in the laboratory but XRay examination, on the other hand, showed appearances of osteocondensation. In the first case, XRay showed both lesions of osteolysis in the cranial vault and homogeneous condensation of D11 and L1, together with the left iliac crest. In the other case, there was osteolysis of the acetabulum together with areas of osteocondensation distributed throughout the pelvis and upper ends of the femurs, with two areas of annular fibrosis circumscribing the area of osteolysis, finally, homogeneous condensation of the skull. In both cases, bone biopsy confirmed the diagnosis of multiple myeloma showing both osteofibrosis and plasma cell infiltration of the bone marrow. This also permitted the authors to note the absence of any myelofibrosis or metamorphic neo-osteogenesis. Illustrated by these two cases, condensing multiple myeloma is a rare entity, the special clinical characteristics of which reside in its fairly frequent coexistence with peripheral neuritis which is probably similar to a para-neoplastic syndrome. The radiological appearances are mainly of four types: 1) Focal areas of bony condensation. 2) Areas of annular fibrosis circumscribing osteolysis. 3) Appearances of radial spicules, or 4) Osteocondensation extending to a fairly large part of the skeleton. The laboratory signs are identical with those in other types of multiple myeloma with a few exceptions, such as, rareness of hypercalcemia, more frequent tendency to hypocalcemia, rise in alkaline phosphatase, in a few cases. Bone biopsy confirms the diagnosis. The osteofibrosis resulted here from thickening of the osteoid seams by laying down of successive layers of bony substance, irregularly calcified and, also secondarily, metamorphic neo-osteogenesis in a few rare cases which also included myelofibrosis."} {"id": "PMID:166442", "title": "[Results of 79 hepatic biopsies in untreated bacillary pleurs pulmonary tuberculosis patients].", "content": "The authors report 79 needle biopsies of the liver, using a Menghini needle, carried out as routine in untreated cases of pulmonary tuberculosis with positive sputum. Apart from the histological study, the authors carried out, in 30 cases, a bacteriological study of the liver fragment. The bacteriological and histological results are reported here in detail, then compared with those in the world literature. No significant correlation was found between the histological type of the suggestive hepatic lesions, e.g. follicular appearances or appearances of nodular k\u00fcpferian hyperplasia and the radioclinical variety of pulmonary tuberculosis, e.g. parenchymatous, pleural or miliary. The authors emphasize the significance of each type of pathological lesion encountered, in particular, the appearance of nodular k\u00fcpferian hyperplasia or intralobular, lymphohistiocytic islets, which seem to them remarkable by their relative frequency and their chararacter fairly suggestive of tuberculosis. In spite of the low number of pathological appearances obtained in these liver biopsies, the present study nevertheless permitted a few interesting conclusions on the blood spread of the tubercle bacillus and the significance of changes in the K\u00fcpfer system during common pulmonary tuberculosis.", "contents": "[Results of 79 hepatic biopsies in untreated bacillary pleurs pulmonary tuberculosis patients]. The authors report 79 needle biopsies of the liver, using a Menghini needle, carried out as routine in untreated cases of pulmonary tuberculosis with positive sputum. Apart from the histological study, the authors carried out, in 30 cases, a bacteriological study of the liver fragment. The bacteriological and histological results are reported here in detail, then compared with those in the world literature. No significant correlation was found between the histological type of the suggestive hepatic lesions, e.g. follicular appearances or appearances of nodular k\u00fcpferian hyperplasia and the radioclinical variety of pulmonary tuberculosis, e.g. parenchymatous, pleural or miliary. The authors emphasize the significance of each type of pathological lesion encountered, in particular, the appearance of nodular k\u00fcpferian hyperplasia or intralobular, lymphohistiocytic islets, which seem to them remarkable by their relative frequency and their chararacter fairly suggestive of tuberculosis. In spite of the low number of pathological appearances obtained in these liver biopsies, the present study nevertheless permitted a few interesting conclusions on the blood spread of the tubercle bacillus and the significance of changes in the K\u00fcpfer system during common pulmonary tuberculosis."} {"id": "PMID:166443", "title": "[Diagnostic and therapeutic problems posed by 2 cases of exudative enteropathy].", "content": "The authors report two cases of exsudative enteropathy characterised by the existence of oedema of the lower limbs associated with hypoproteinemia and marked lymphopenia with disturbances of the P.V.P. test. In both cases lymphography demonstrated major abnormalities with obvious obstruction in one case, and signs of slowing of lymph flow with appearances of dysplasia in the other. Surgery permitted us in one case, to discover a calcified lymph node probably due to tuberculosis. The etiology of these cases is discussed and seems to be mainly related to abnormalities of the lymphatic system. A low fat diet and administration of medium-chain triglycerides, gave an undoubted improvement when the treatment was followed by the patient. These two cases illustrate well the difficult diagnostic and therapeutic problems sometimes raised by syndromes of exsudative enteropathy, in particular owing to the many possible causes.", "contents": "[Diagnostic and therapeutic problems posed by 2 cases of exudative enteropathy]. The authors report two cases of exsudative enteropathy characterised by the existence of oedema of the lower limbs associated with hypoproteinemia and marked lymphopenia with disturbances of the P.V.P. test. In both cases lymphography demonstrated major abnormalities with obvious obstruction in one case, and signs of slowing of lymph flow with appearances of dysplasia in the other. Surgery permitted us in one case, to discover a calcified lymph node probably due to tuberculosis. The etiology of these cases is discussed and seems to be mainly related to abnormalities of the lymphatic system. A low fat diet and administration of medium-chain triglycerides, gave an undoubted improvement when the treatment was followed by the patient. These two cases illustrate well the difficult diagnostic and therapeutic problems sometimes raised by syndromes of exsudative enteropathy, in particular owing to the many possible causes."} {"id": "PMID:166444", "title": "[Supravermian subdural triangle limited by the veins of the posterior fossa. Normal radio-anatomical study. Vermis herniation in the supravermian subdural space or superior vermis herniation].", "content": "The author describes a conical sub-dural space above the vermis limited in front by Galien's ampulla, behind by the right venous sinuses and, below by the superior cerebellar vein. This space, which is not filled with air injected by the cisternal route, is only shown in lateral views thanks to its venous outlines. In cases of raised intracranial pressure, the superior cerebellar vermis may occupy this space so that a sort of impaction occurs at this level, which the author proposes calling smaller than superior vermial impaction greater than. Among forms of cerebral herniation, vermial impaction may not occur when the CSF obstruction occurs at another level.", "contents": "[Supravermian subdural triangle limited by the veins of the posterior fossa. Normal radio-anatomical study. Vermis herniation in the supravermian subdural space or superior vermis herniation]. The author describes a conical sub-dural space above the vermis limited in front by Galien's ampulla, behind by the right venous sinuses and, below by the superior cerebellar vein. This space, which is not filled with air injected by the cisternal route, is only shown in lateral views thanks to its venous outlines. In cases of raised intracranial pressure, the superior cerebellar vermis may occupy this space so that a sort of impaction occurs at this level, which the author proposes calling smaller than superior vermial impaction greater than. Among forms of cerebral herniation, vermial impaction may not occur when the CSF obstruction occurs at another level."} {"id": "PMID:166445", "title": "[Malignant lymphoma with pulmonary localization. Attempt at an anatomo-pathological classification].", "content": "The authors reported 33 cases of malignant lymphoma in the lung observed over a period of 6 years on the Pathological Department of the Beaujon Hospital. Whatever their cytological, lymphocytic, lymphoblastic or reticular type (Hodgkin's disease was excluded from this study), they may be grouped in two main pathological categories: 1) Malignant lymphoma involving the lung and mediastinum without extra-thoracic lesions detected at the time of diagnosis (4 cases). In 3 cases, the disease had been present for 2 to 6 months. In 1 case the course was favourable for 5 years then the patient developed acute lymphoblastic leukemia. 2) The pulmonary lesions observed during general infections, whether as presenting symptoms in 9 cases, or simply discovered on autopsy as in 20 cases. Histological examination, essential for the diagnosis of malignant lymphoma, provides no evidence in favour of the primary pulmonary origin of the disease; this diagnosis can only be made after full blood investigations. The prognosis is also difficult to determine for survival for many years may be followed by sudden general malignant blood disease.", "contents": "[Malignant lymphoma with pulmonary localization. Attempt at an anatomo-pathological classification]. The authors reported 33 cases of malignant lymphoma in the lung observed over a period of 6 years on the Pathological Department of the Beaujon Hospital. Whatever their cytological, lymphocytic, lymphoblastic or reticular type (Hodgkin's disease was excluded from this study), they may be grouped in two main pathological categories: 1) Malignant lymphoma involving the lung and mediastinum without extra-thoracic lesions detected at the time of diagnosis (4 cases). In 3 cases, the disease had been present for 2 to 6 months. In 1 case the course was favourable for 5 years then the patient developed acute lymphoblastic leukemia. 2) The pulmonary lesions observed during general infections, whether as presenting symptoms in 9 cases, or simply discovered on autopsy as in 20 cases. Histological examination, essential for the diagnosis of malignant lymphoma, provides no evidence in favour of the primary pulmonary origin of the disease; this diagnosis can only be made after full blood investigations. The prognosis is also difficult to determine for survival for many years may be followed by sudden general malignant blood disease."} {"id": "PMID:166448", "title": "Predictability of response to endocrine ablation in breast cancer.", "content": "Carcinoma of the breast remains the most common and most frequently lethal form of cancer in women. In far-advanced disease, endocrine manipulation remains the major modality of treatment. Recent advances have shown that approximately 40% of breast cancers contain estradiol receptors in their cytoplasm. The presence or absence of these receptors is a good indicator of whether or not the patient will respond to endocrine ablation.", "contents": "Predictability of response to endocrine ablation in breast cancer. Carcinoma of the breast remains the most common and most frequently lethal form of cancer in women. In far-advanced disease, endocrine manipulation remains the major modality of treatment. Recent advances have shown that approximately 40% of breast cancers contain estradiol receptors in their cytoplasm. The presence or absence of these receptors is a good indicator of whether or not the patient will respond to endocrine ablation."} {"id": "PMID:166449", "title": "Friedreich's ataxia.", "content": "The clinical and pathologic findings in Friedreich's ataxia were discussed and recent literature was reviewed with respect to associated heart disease, diabetes mellitus, peripheral nerve involvement, and EEG changes. Recent research aimed toward discovering an enzyme defect or defects was reviewed and, when available, our conclusions were stated. Friedreich's ataxia remains an unexplained spinocerebellar degeneration occurring in early life, inherited in a predominantly autosomal recessive fashion, and associated with cardiac dysfunction, diabetes mellitus, and peripheral sensory nerve involvement.", "contents": "Friedreich's ataxia. The clinical and pathologic findings in Friedreich's ataxia were discussed and recent literature was reviewed with respect to associated heart disease, diabetes mellitus, peripheral nerve involvement, and EEG changes. Recent research aimed toward discovering an enzyme defect or defects was reviewed and, when available, our conclusions were stated. Friedreich's ataxia remains an unexplained spinocerebellar degeneration occurring in early life, inherited in a predominantly autosomal recessive fashion, and associated with cardiac dysfunction, diabetes mellitus, and peripheral sensory nerve involvement."} {"id": "PMID:166451", "title": "Cytomegalic virus infection of bowel in adults.", "content": "Cytomegalic virus infection of the bowel in 2 adult patients is reported. The controversies related to this rare pathology are evaluated, particularly the role of cytomegalic inclusion virus (CMV) as a primary or secondary pathogen in bowel.", "contents": "Cytomegalic virus infection of bowel in adults. Cytomegalic virus infection of the bowel in 2 adult patients is reported. The controversies related to this rare pathology are evaluated, particularly the role of cytomegalic inclusion virus (CMV) as a primary or secondary pathogen in bowel."} {"id": "PMID:166452", "title": "Paediatric renal masses. Some experiences with ultrasound and arteriography.", "content": "Renal masses in children are common, their pathology varying in different age groups. Using ultrasound to establish a diagnosis, the supine position should first be attempted. For black-and-white echography a medium frequency of 2,5 megahertz is suitable, but careful technique and interpretation are essential. Arteriography using a 70-mm camera is not suitable for selective evaluation of avascular masses. Four illustrative cases to show diagnostic points and pitfalls are recorded.", "contents": "Paediatric renal masses. Some experiences with ultrasound and arteriography. Renal masses in children are common, their pathology varying in different age groups. Using ultrasound to establish a diagnosis, the supine position should first be attempted. For black-and-white echography a medium frequency of 2,5 megahertz is suitable, but careful technique and interpretation are essential. Arteriography using a 70-mm camera is not suitable for selective evaluation of avascular masses. Four illustrative cases to show diagnostic points and pitfalls are recorded."} {"id": "PMID:166453", "title": "The radiological diagnosis of hepatoma with special emphasis on angiography.", "content": "The radiological findings of 69 out of a total of 81 cases of proven primary hepatocellular carcinoma are reviewed retrospectively. Selective angiography was performed on 42 patients and the results are analysed according to specific angiographic findings and distribution of the neoplasm, Because of the more aggressive approach to surgical treatment of hepatomas, angiography is of utmost importance in the pre-operative evaluation of the extent of the lesion and the vascular supply to the liver. Apart from the conventional angiogram, the technique of slow-infusion hepatic angiography is discussed as well as the value of enhancement techniques such as photographic subtraction and the use of vasoconstrictor drugs. Response to chemotherapy can be assessed by an infusion hepatic angiogram if a catheter has been surgically placed in the hepatic artery. The majority of tumours were easily disgnosed on the angiogram but special problems were encountered in distinguishing multicentric forms of hepatoma from hepatic metastases and avascular lesions from primary cholangiocarcinoma. The wide variety of clinical and angiographic findings that may be found, are emphasised in 4 brief case repots.", "contents": "The radiological diagnosis of hepatoma with special emphasis on angiography. The radiological findings of 69 out of a total of 81 cases of proven primary hepatocellular carcinoma are reviewed retrospectively. Selective angiography was performed on 42 patients and the results are analysed according to specific angiographic findings and distribution of the neoplasm, Because of the more aggressive approach to surgical treatment of hepatomas, angiography is of utmost importance in the pre-operative evaluation of the extent of the lesion and the vascular supply to the liver. Apart from the conventional angiogram, the technique of slow-infusion hepatic angiography is discussed as well as the value of enhancement techniques such as photographic subtraction and the use of vasoconstrictor drugs. Response to chemotherapy can be assessed by an infusion hepatic angiogram if a catheter has been surgically placed in the hepatic artery. The majority of tumours were easily disgnosed on the angiogram but special problems were encountered in distinguishing multicentric forms of hepatoma from hepatic metastases and avascular lesions from primary cholangiocarcinoma. The wide variety of clinical and angiographic findings that may be found, are emphasised in 4 brief case repots."} {"id": "PMID:166454", "title": "Klippel-Trenaunay syndrome. A case report and review of the literature.", "content": "Clinical and radiological assessment of a female patient suffering from varicose veins revealed many of the features first described by Klippel and Trenaunay. The findings are presented in detail and the lymphographic features are illustrated. The previous literature is briefly reviewed.", "contents": "Klippel-Trenaunay syndrome. A case report and review of the literature. Clinical and radiological assessment of a female patient suffering from varicose veins revealed many of the features first described by Klippel and Trenaunay. The findings are presented in detail and the lymphographic features are illustrated. The previous literature is briefly reviewed."} {"id": "PMID:166455", "title": "Liver pathology in alpha1-antitrypsin deficiency. A review.", "content": "Alpha1-antitrypsin deficiency (AATD), in addition to its association with chronic pulmonary disease, is reported with liver disease. Twenty per cent of Pi-type ZZ AATD infants present with a cholestatic type of neonatal hepatitis and develop a slowly progressive cirrhosis, and most die before adult life. Ten per cent of Pi-type ZZ adults develop cirrhosis. They have an increased frequency of primary liver carcinoma. In Z homozygotes and heterozygotes specific globules, due to accumulation of a type of alpha1-antitrypsin, are seen in liver cells. They are thought not to be hepatotoxic but to render the liver cell more susceptible to damage by an additional factor.", "contents": "Liver pathology in alpha1-antitrypsin deficiency. A review. Alpha1-antitrypsin deficiency (AATD), in addition to its association with chronic pulmonary disease, is reported with liver disease. Twenty per cent of Pi-type ZZ AATD infants present with a cholestatic type of neonatal hepatitis and develop a slowly progressive cirrhosis, and most die before adult life. Ten per cent of Pi-type ZZ adults develop cirrhosis. They have an increased frequency of primary liver carcinoma. In Z homozygotes and heterozygotes specific globules, due to accumulation of a type of alpha1-antitrypsin, are seen in liver cells. They are thought not to be hepatotoxic but to render the liver cell more susceptible to damage by an additional factor."} {"id": "PMID:166456", "title": "Some aspects of corticosteroid-induced cleft palate: a review.", "content": "Since the discovery 25 years ago that cortisone can produce cleft palate in mouse embryos investigations into possible mechanisms of this corticosteroid-induced defect have been many and varied. However, the teratogenic mode of action remains not fully clarified. It is with this thought in mind that we have reflected upon what is known concerning corticosteroids and cleft palate. The major metabolic pathways upon which glucocorticoids act as well as their intracellular mode of action are well known. Differential sensitivity of various mouse strains to cortisone treatment as well as recent results from interstrain blastocyst transfer experiments demonstrate that corticosteroid action is influenced by both the fetal and maternal genomes. Labeling experiments indicate that corticosteroid-induced cleft palate is the result of direct action of the steroid molecule on the fetus, whose own sensitivity to insult, perhaps owing to differences in binding of corticosteroids to tissue proteins, determines the final effect. Possible mechanisms that have been proposed by which corticoids may produce cleft palate include: disruption of glycosaminoglycan or collagen synthesis or both, intracellular lysosomal membrane stabilization, myopathy, weakened midline fusion, and loss of amniotic fluid. Also discussed is the role of stress and stress-induced corticosteroids and their possible role in the production of cleft palate.", "contents": "Some aspects of corticosteroid-induced cleft palate: a review. Since the discovery 25 years ago that cortisone can produce cleft palate in mouse embryos investigations into possible mechanisms of this corticosteroid-induced defect have been many and varied. However, the teratogenic mode of action remains not fully clarified. It is with this thought in mind that we have reflected upon what is known concerning corticosteroids and cleft palate. The major metabolic pathways upon which glucocorticoids act as well as their intracellular mode of action are well known. Differential sensitivity of various mouse strains to cortisone treatment as well as recent results from interstrain blastocyst transfer experiments demonstrate that corticosteroid action is influenced by both the fetal and maternal genomes. Labeling experiments indicate that corticosteroid-induced cleft palate is the result of direct action of the steroid molecule on the fetus, whose own sensitivity to insult, perhaps owing to differences in binding of corticosteroids to tissue proteins, determines the final effect. Possible mechanisms that have been proposed by which corticoids may produce cleft palate include: disruption of glycosaminoglycan or collagen synthesis or both, intracellular lysosomal membrane stabilization, myopathy, weakened midline fusion, and loss of amniotic fluid. Also discussed is the role of stress and stress-induced corticosteroids and their possible role in the production of cleft palate."} {"id": "PMID:166457", "title": "Tissue phosphatase changes following triamcinolone associated with cleft palate in rats.", "content": "One theory of the development of cleft palate in rats involves the action of lysosomal enzymes secreted by epithelial cells at the time of fusion of the palatal shelves. To test this theory we studied the biochemistry of the palates of fetal rats daily between days 14 and 19 (from 3 days before to 3 days after palate closure). Triamcinolone was administered once im on gestation day 14 to Wistar rats; 0.5 mg/kg body weight produced approximately 50% cleft palates. Pooled control palatal tissue was compared with pooled experimental tissue; that from fetuses with clefts being pooled separately from those not affected. Acid phosphatase and beta-glucuronidase were assayed. Concentration vs. time curves for both enzymes were very similar. Prior to the time of palate closure both enzymes were present in low concentration. Between days 16 and 17, the normal time of closure, there was an abrupt increased in enzyme concentration, with experimental tissue showing a significant elevation over control tissue on days 17 and 18. Alkaline phosphatase was also present in small amounts before closure and significantly higher in control tissue on day 17. Protein was depressed in palates having clefts on day 17; thus the ratio of enzyme activities to protein synthesis was significantly elevated at a critical time. Unaffected experimental palates had a normal ratio. These results suggest imbalanced acid phosphatase, beta-glucuronidase, and alkaline phosphatase activity compared with protein synthesis at the time of palate closure following triamcinolone in rats.", "contents": "Tissue phosphatase changes following triamcinolone associated with cleft palate in rats. One theory of the development of cleft palate in rats involves the action of lysosomal enzymes secreted by epithelial cells at the time of fusion of the palatal shelves. To test this theory we studied the biochemistry of the palates of fetal rats daily between days 14 and 19 (from 3 days before to 3 days after palate closure). Triamcinolone was administered once im on gestation day 14 to Wistar rats; 0.5 mg/kg body weight produced approximately 50% cleft palates. Pooled control palatal tissue was compared with pooled experimental tissue; that from fetuses with clefts being pooled separately from those not affected. Acid phosphatase and beta-glucuronidase were assayed. Concentration vs. time curves for both enzymes were very similar. Prior to the time of palate closure both enzymes were present in low concentration. Between days 16 and 17, the normal time of closure, there was an abrupt increased in enzyme concentration, with experimental tissue showing a significant elevation over control tissue on days 17 and 18. Alkaline phosphatase was also present in small amounts before closure and significantly higher in control tissue on day 17. Protein was depressed in palates having clefts on day 17; thus the ratio of enzyme activities to protein synthesis was significantly elevated at a critical time. Unaffected experimental palates had a normal ratio. These results suggest imbalanced acid phosphatase, beta-glucuronidase, and alkaline phosphatase activity compared with protein synthesis at the time of palate closure following triamcinolone in rats."} {"id": "PMID:166461", "title": "[Results of combined Wilms tumor therapy with special reference to therapy-induced skeletal changes].", "content": "Prognosis of Wilms' tumors has remarkably improved by combination of surgery, radiation and chemotherapy. Incidence and extent of skeletal changes after standardized treatment (1967-1973) of 24 children were analysed in dependence on time of therapy and age.", "contents": "[Results of combined Wilms tumor therapy with special reference to therapy-induced skeletal changes]. Prognosis of Wilms' tumors has remarkably improved by combination of surgery, radiation and chemotherapy. Incidence and extent of skeletal changes after standardized treatment (1967-1973) of 24 children were analysed in dependence on time of therapy and age."} {"id": "PMID:166462", "title": "Radioactive ruthenium red accumulation by tumors: a potential scanning agent.", "content": "The distribution of 103-Ru-Ruthenium red in tumour bearing animals indicates that Ruthenium red labelled with radioruthenium shows the characteristics of a tumour scanning agent. Its accumulation seems to be related to its specific binding to mucopolysaccharides. In addition, this radiocompound shows a potential value in the study of other pathological states involving the metabolism of mucopolysaccharides and glycoproteins.", "contents": "Radioactive ruthenium red accumulation by tumors: a potential scanning agent. The distribution of 103-Ru-Ruthenium red in tumour bearing animals indicates that Ruthenium red labelled with radioruthenium shows the characteristics of a tumour scanning agent. Its accumulation seems to be related to its specific binding to mucopolysaccharides. In addition, this radiocompound shows a potential value in the study of other pathological states involving the metabolism of mucopolysaccharides and glycoproteins."} {"id": "PMID:166465", "title": "The human mixed lymphocyte-endothelium culture interaction.", "content": "Cells separated from the wall of the umbilical cord vein by collagenase digestion could be identified as endothelial by their characteristic ultrastructure, their growth pattern in culture, and their microscopical morphology. These cells, both freshly explanted and after long-term culturing, were capable of stimulating allogeneic lymphocytes in vitro. Control experiments indicated that this stimulation was not attributable to contamination of the endothelial cell suspensions by foetal fibroblasts or passenger lymphocytes. The dose response characteristics and kinetics of the lymphoproliferative response using endothelial stimulating cells was similar to mixed lymphocyte cultures. Sera which were capable of inhibiting the mixed lymphocyte culture response were relatively ineffective in inhibiting the stimulation caused by endothelial cells.", "contents": "The human mixed lymphocyte-endothelium culture interaction. Cells separated from the wall of the umbilical cord vein by collagenase digestion could be identified as endothelial by their characteristic ultrastructure, their growth pattern in culture, and their microscopical morphology. These cells, both freshly explanted and after long-term culturing, were capable of stimulating allogeneic lymphocytes in vitro. Control experiments indicated that this stimulation was not attributable to contamination of the endothelial cell suspensions by foetal fibroblasts or passenger lymphocytes. The dose response characteristics and kinetics of the lymphoproliferative response using endothelial stimulating cells was similar to mixed lymphocyte cultures. Sera which were capable of inhibiting the mixed lymphocyte culture response were relatively ineffective in inhibiting the stimulation caused by endothelial cells."} {"id": "PMID:166466", "title": "Prevalence of cardiac tumours at autopsy in Ibadan.", "content": "The post mortem specimens, protocols, slides and hospital case notes of 6064 necropsies carried out in the University College Hospital, Ibadan over a seven year period were reviewed. Cardiac tumours were found in 64 subjects (1.06%) of all autopsies and in 8.5% of all 752 malignancies that came to autopsy during the same period. Only two of these tumours arose primarily in the heart whilst the remaining were metastatic tumours. The right side of the heart was more often involved than any other part (31.38%). The tumour with the highest cardiac involvement was Burkitt's lymphoma with an incidence of 30 cases i.e. 8.24% of all malignancies; 0.48% of all necropsies studied; 53.6% of all Burkitt's lymphoma autopsied. The risk of associating the rate of cardiac involvement of any tumour with its index of higher frequency was emphasized in the light of the paucity of involvement in a more frequent malignancy (hepatocellular) carcinoma in this environment. Routine medical examination coupled with an awareness of the possible susceptibility of the heart to secondary involvement by Burkitt's lymphoma would aid ante-mortem diagnosis of intracardiac malignancy particularly in patients of Burkitt's lymphoma age group.", "contents": "Prevalence of cardiac tumours at autopsy in Ibadan. The post mortem specimens, protocols, slides and hospital case notes of 6064 necropsies carried out in the University College Hospital, Ibadan over a seven year period were reviewed. Cardiac tumours were found in 64 subjects (1.06%) of all autopsies and in 8.5% of all 752 malignancies that came to autopsy during the same period. Only two of these tumours arose primarily in the heart whilst the remaining were metastatic tumours. The right side of the heart was more often involved than any other part (31.38%). The tumour with the highest cardiac involvement was Burkitt's lymphoma with an incidence of 30 cases i.e. 8.24% of all malignancies; 0.48% of all necropsies studied; 53.6% of all Burkitt's lymphoma autopsied. The risk of associating the rate of cardiac involvement of any tumour with its index of higher frequency was emphasized in the light of the paucity of involvement in a more frequent malignancy (hepatocellular) carcinoma in this environment. Routine medical examination coupled with an awareness of the possible susceptibility of the heart to secondary involvement by Burkitt's lymphoma would aid ante-mortem diagnosis of intracardiac malignancy particularly in patients of Burkitt's lymphoma age group."} {"id": "PMID:166474", "title": "Ultrastructural-morphometric analysis of the rat prostate (ventral lobe).", "content": "A morphometric model, which provides information on the structure of the normal gland (ventral lobe) has been developed for the rat prostate. The model consists of morphologically defined space and membrane compartments, which are used to describe the specific components of the protein and enzyme synthesizing and secreting glandular cells. The results presented are relative to a cubic centimeter of prostatic tissue, a cubic centimeter of acinar parenchyma and glandular cell cytoplasm. Special interest was given to the cell compartments which are involved in protein and enzyme synthesis.", "contents": "Ultrastructural-morphometric analysis of the rat prostate (ventral lobe). A morphometric model, which provides information on the structure of the normal gland (ventral lobe) has been developed for the rat prostate. The model consists of morphologically defined space and membrane compartments, which are used to describe the specific components of the protein and enzyme synthesizing and secreting glandular cells. The results presented are relative to a cubic centimeter of prostatic tissue, a cubic centimeter of acinar parenchyma and glandular cell cytoplasm. Special interest was given to the cell compartments which are involved in protein and enzyme synthesis."} {"id": "PMID:166475", "title": "Retroperitoneal renal transplantation in young children.", "content": "Children with urologic causes of renal failure constitute an increasing percentage of patients requiring transplantation. Two children weighing less than 20 Kg. underwent successful transplantation despite multiple previous intra-abdominal procedures. The retroperitoneal technique employed for these patients is described and its advantages emphasized.", "contents": "Retroperitoneal renal transplantation in young children. Children with urologic causes of renal failure constitute an increasing percentage of patients requiring transplantation. Two children weighing less than 20 Kg. underwent successful transplantation despite multiple previous intra-abdominal procedures. The retroperitoneal technique employed for these patients is described and its advantages emphasized."} {"id": "PMID:166476", "title": "Beneficial effects of adriamycin on Wistar-Furth Wilms' tumor.", "content": "The Wilms' tumor (Wistar-Furth, Columbia University) animal model kills the host in a predictable period of time, associated with widespread metastases (lungs, liver, spleen) regardless of the route of tumor transplantation. Actinomycin D in single or multiple doses has previously been shown to increase survival, reduce the primary tumor weight, as well as the number of metastases in this experimental model. The model thus has close similarity to man. The present report describes a remarkable effect of adriamycin in this animal system. The beneficial results are, however, limited by severe dose-related toxicity. Nevertheless, faced with recurrent or metastatic lesions following prior current conventional clinical therapy, based on the present experimental results, we believe adriamycin treatment should be given serious clinical consideration.", "contents": "Beneficial effects of adriamycin on Wistar-Furth Wilms' tumor. The Wilms' tumor (Wistar-Furth, Columbia University) animal model kills the host in a predictable period of time, associated with widespread metastases (lungs, liver, spleen) regardless of the route of tumor transplantation. Actinomycin D in single or multiple doses has previously been shown to increase survival, reduce the primary tumor weight, as well as the number of metastases in this experimental model. The model thus has close similarity to man. The present report describes a remarkable effect of adriamycin in this animal system. The beneficial results are, however, limited by severe dose-related toxicity. Nevertheless, faced with recurrent or metastatic lesions following prior current conventional clinical therapy, based on the present experimental results, we believe adriamycin treatment should be given serious clinical consideration."} {"id": "PMID:166477", "title": "Ectopic ACTH production in disseminated prostatic adenocarcinoma.", "content": "The second fully documented case of ACTH-producing prostatic adenocarcinoma with elevated plasma and tissue levels of ACTH is presented. The distinguishing characteristics of ACTH-producing extrapituitary neoplasms and the various modes of therapy are discussed.", "contents": "Ectopic ACTH production in disseminated prostatic adenocarcinoma. The second fully documented case of ACTH-producing prostatic adenocarcinoma with elevated plasma and tissue levels of ACTH is presented. The distinguishing characteristics of ACTH-producing extrapituitary neoplasms and the various modes of therapy are discussed."} {"id": "PMID:166479", "title": "Asymmetric hindquarter syndrome (AHQS) in the pig.", "content": "Outbreaks of the asymmetric hindquarter syndrome (AHQS) in two pig herds are reported together with the results of test matings and dissection studies on affected pigs. The condition (apparently identical with that described in Germany in 1967), is characterised by a variable asymmetry of the hindquarters and particularly of individual muscles of the posterior, lateral and medial aspects of the thigh. It does not noticeably interfere with locomotion but can adversely affect carcase conformation and may detract from the usefulness of carcase dissection studies as a basis for genetic selection. AHQS has a familial incidence and is usually first detected clinically after weaning. A variety of degenerative and dystrophic changes have been seen in the muscles of AHQS pigs but these are not constantly present in nor confined to 'undersized' muscles. The precise aetiology of AHQS is still unresolved but it is concluded that it probably occurs post-natally and that some pigs have a genetic liability to develop the condition.", "contents": "Asymmetric hindquarter syndrome (AHQS) in the pig. Outbreaks of the asymmetric hindquarter syndrome (AHQS) in two pig herds are reported together with the results of test matings and dissection studies on affected pigs. The condition (apparently identical with that described in Germany in 1967), is characterised by a variable asymmetry of the hindquarters and particularly of individual muscles of the posterior, lateral and medial aspects of the thigh. It does not noticeably interfere with locomotion but can adversely affect carcase conformation and may detract from the usefulness of carcase dissection studies as a basis for genetic selection. AHQS has a familial incidence and is usually first detected clinically after weaning. A variety of degenerative and dystrophic changes have been seen in the muscles of AHQS pigs but these are not constantly present in nor confined to 'undersized' muscles. The precise aetiology of AHQS is still unresolved but it is concluded that it probably occurs post-natally and that some pigs have a genetic liability to develop the condition."} {"id": "PMID:166480", "title": "Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus.", "content": "The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli.", "contents": "Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus. The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli."} {"id": "PMID:166481", "title": "Effect of citrate and aminotriazole on matrical plates induced in hepatic microbodies.", "content": "Feeding of acetylsalicylic acid (ASA), clofibrate and dimethrin induces formation of matrical plates in heptaic microbodies. Administration of sodium citrate prevents formation of matrical plates in rats fed ASA, but not in rats treated with clofibrate or dimethrin. Propionate has a similar effect on rats fed ASA but not those fed clofibrate. Feeding of aminotriazole prevents formation of matrical plates in rats fed ASA without inhibiting the proliferation of microbodies. Sodium citrate and aminotriazole and feeding decrease also the activity of hepatic catalase in rats fed ASA.", "contents": "Effect of citrate and aminotriazole on matrical plates induced in hepatic microbodies. Feeding of acetylsalicylic acid (ASA), clofibrate and dimethrin induces formation of matrical plates in heptaic microbodies. Administration of sodium citrate prevents formation of matrical plates in rats fed ASA, but not in rats treated with clofibrate or dimethrin. Propionate has a similar effect on rats fed ASA but not those fed clofibrate. Feeding of aminotriazole prevents formation of matrical plates in rats fed ASA without inhibiting the proliferation of microbodies. Sodium citrate and aminotriazole and feeding decrease also the activity of hepatic catalase in rats fed ASA."} {"id": "PMID:166513", "title": "[Study of glycogen metabolism in the liver in type III glycogenosis (limit dextrinosis)].", "content": "Data on biochemical study of a patient with glycogenosis of the III type (limit dextrinosis) are presented. In a punctate of liver tissue absence of amylo-1,6-glucosidase activity and significant accumulation of glycogen, which was anomalous in structure, were noted. Loading with galactose and adrenaline caused alterations typical for the III type of glycogenosis. Content of glucose and lactate in blood were also studied in response to the peroral administration of glucose and protein. In erythrocytes of the patient the polysaccharide structure was shown to be anomalous; it resembled the structure of a polysaccharide from liver tissue of the patient.", "contents": "[Study of glycogen metabolism in the liver in type III glycogenosis (limit dextrinosis)]. Data on biochemical study of a patient with glycogenosis of the III type (limit dextrinosis) are presented. In a punctate of liver tissue absence of amylo-1,6-glucosidase activity and significant accumulation of glycogen, which was anomalous in structure, were noted. Loading with galactose and adrenaline caused alterations typical for the III type of glycogenosis. Content of glucose and lactate in blood were also studied in response to the peroral administration of glucose and protein. In erythrocytes of the patient the polysaccharide structure was shown to be anomalous; it resembled the structure of a polysaccharide from liver tissue of the patient."} {"id": "PMID:166514", "title": "[Action of deoxyadenosine on nucleic acid synthesis by tumor cells in the presence of a deaminase inhibitor].", "content": "Deoxyadenosine, which was phosphorylated to dATP, inhibited DNA synthesis in malignant cells. However, on incubation of the substance in vitro with Zaidela ascites hepatoma cells the inhibitory effect was gradually decreased due to dephosphorylation of dATP and to deamination of deoxyadenosine to deoxyinosine. In order to prolong the inhibition of nucleic acids synthesis, N-6-methyl adenosine, which was recognized as an inhibitor of adenosine deaminase, was added to the cells. Optimal inhibition of DNA synthesis was observed in presence of deoxyadenosine and N-6-methyl adenosine at 1 with 10-minus 3 M concentration. Addition of N-6-methyl adenosine, after incubation with deoxyadenosine within 2 hrs, caused more prolonged inhibition of DNA and RNA synthesis than it was observed in presence of deoxyadenosine.", "contents": "[Action of deoxyadenosine on nucleic acid synthesis by tumor cells in the presence of a deaminase inhibitor]. Deoxyadenosine, which was phosphorylated to dATP, inhibited DNA synthesis in malignant cells. However, on incubation of the substance in vitro with Zaidela ascites hepatoma cells the inhibitory effect was gradually decreased due to dephosphorylation of dATP and to deamination of deoxyadenosine to deoxyinosine. In order to prolong the inhibition of nucleic acids synthesis, N-6-methyl adenosine, which was recognized as an inhibitor of adenosine deaminase, was added to the cells. Optimal inhibition of DNA synthesis was observed in presence of deoxyadenosine and N-6-methyl adenosine at 1 with 10-minus 3 M concentration. Addition of N-6-methyl adenosine, after incubation with deoxyadenosine within 2 hrs, caused more prolonged inhibition of DNA and RNA synthesis than it was observed in presence of deoxyadenosine."} {"id": "PMID:166515", "title": "[Liver hexokinase isoenzymes in carcinogenesis].", "content": "Four isoenzymes of hexokinase were isolated by means of chromatography on DEAE-cellulose from soluble fraction of Vistar rat liver tissue. One of the isoenzymes (IV) was a glucokinase. Four fractions were also found in starch gel electrophoresis. These fractions catalyzed phosphorylation of glucose. Besides alterations in the total activity of hexokinase the changes in isoenzyme spectra were observed in carcinogenesis, caused by diethyl nitrosoamine. In the course of development of the blastomatose process in liver tissue content of isoenzymes I, II and, especially, of III was increased, and content of isoenzyme IV was decreased. In tissue of primary hepatomas, induced by diethyl nitrosoamine, the isoenzyme spectra of hexokinase did not significantly differ from the spectra of the enzyme in liver tissue at later stages of carcinogenesis.", "contents": "[Liver hexokinase isoenzymes in carcinogenesis]. Four isoenzymes of hexokinase were isolated by means of chromatography on DEAE-cellulose from soluble fraction of Vistar rat liver tissue. One of the isoenzymes (IV) was a glucokinase. Four fractions were also found in starch gel electrophoresis. These fractions catalyzed phosphorylation of glucose. Besides alterations in the total activity of hexokinase the changes in isoenzyme spectra were observed in carcinogenesis, caused by diethyl nitrosoamine. In the course of development of the blastomatose process in liver tissue content of isoenzymes I, II and, especially, of III was increased, and content of isoenzyme IV was decreased. In tissue of primary hepatomas, induced by diethyl nitrosoamine, the isoenzyme spectra of hexokinase did not significantly differ from the spectra of the enzyme in liver tissue at later stages of carcinogenesis."} {"id": "PMID:166522", "title": "[Hypoglycaemic coma in Boeck's sarcoidosis (author's transl)].", "content": "The diversity of clinical manifestations of Boeck's sarcoidosis may also include endocrine disorders. One year after diagnosis of sarcoidosis in a 29 year-old female patient, endocrinological complications became manifest with amenorrhoea. The course of the disease was additionally complicated by hypoglycaemic episodes. Thorough clinical investigation of the patient revealed sarcoid involvement of the skin, lungs, liver and lymph nodes and an extensive retroperitoneal surgically-verified lymph tumour. After tolbutamide and in reaction to an intravenous glucose tolerance test the blood glucose was found to be very low, whilst the immunoreactive insulin was normal. Further investigation of the endocrine functions of the patient revealed normal functioning of the thyroid gland, subnormal values for the follicle stimulating hormone and extremely low serum ACTH and serum cortisol values, without any diurnal changes in these parameters. The clinical symptoms of the patient and the biochemical findings were regarded as manifestations of secondary adrenal failure due to sarcoid involvement of the hypothalamus and pituitary. Hence, treatment with corticosteroids was started. Hypoglycaemia has not since been observed in this patient and the other clinical features of (secondary) adrenal failure have disappeared slowly.", "contents": "[Hypoglycaemic coma in Boeck's sarcoidosis (author's transl)]. The diversity of clinical manifestations of Boeck's sarcoidosis may also include endocrine disorders. One year after diagnosis of sarcoidosis in a 29 year-old female patient, endocrinological complications became manifest with amenorrhoea. The course of the disease was additionally complicated by hypoglycaemic episodes. Thorough clinical investigation of the patient revealed sarcoid involvement of the skin, lungs, liver and lymph nodes and an extensive retroperitoneal surgically-verified lymph tumour. After tolbutamide and in reaction to an intravenous glucose tolerance test the blood glucose was found to be very low, whilst the immunoreactive insulin was normal. Further investigation of the endocrine functions of the patient revealed normal functioning of the thyroid gland, subnormal values for the follicle stimulating hormone and extremely low serum ACTH and serum cortisol values, without any diurnal changes in these parameters. The clinical symptoms of the patient and the biochemical findings were regarded as manifestations of secondary adrenal failure due to sarcoid involvement of the hypothalamus and pituitary. Hence, treatment with corticosteroids was started. Hypoglycaemia has not since been observed in this patient and the other clinical features of (secondary) adrenal failure have disappeared slowly."} {"id": "PMID:166525", "title": "Smith-Lemli-Opitz syndrome: review and report of two affected siblings.", "content": "This paper reports two siblings with the Smith-Lemli-Opitz syndrome and reviews the literature on the subject. SLOS is a syndrome of multiple congenital anomalies with mental and growth retardation, unusual facies, genito-urinary and hand and foot abnormalities inherited as an autosomal recessive trait.", "contents": "Smith-Lemli-Opitz syndrome: review and report of two affected siblings. This paper reports two siblings with the Smith-Lemli-Opitz syndrome and reviews the literature on the subject. SLOS is a syndrome of multiple congenital anomalies with mental and growth retardation, unusual facies, genito-urinary and hand and foot abnormalities inherited as an autosomal recessive trait."} {"id": "PMID:166526", "title": "Giant platelets and fibrin-like inclusions in platelets of BALB/c mice after intraperitoneal inoculation of HIPA tumour agent.", "content": "2 days after ip inoculation of cell-free extracts of HIPA tumour, giant platelets and platelets with band-like inclusions were found in blood of BALB/c mice. Band-like inclusions with platelets have morphologic structure of fibrin. Their presence in the thrombocytes is probably an accidental finding. Giant platelets in the circulating blood are probably due to a disturbed meagacaryocytopoiesis.", "contents": "Giant platelets and fibrin-like inclusions in platelets of BALB/c mice after intraperitoneal inoculation of HIPA tumour agent. 2 days after ip inoculation of cell-free extracts of HIPA tumour, giant platelets and platelets with band-like inclusions were found in blood of BALB/c mice. Band-like inclusions with platelets have morphologic structure of fibrin. Their presence in the thrombocytes is probably an accidental finding. Giant platelets in the circulating blood are probably due to a disturbed meagacaryocytopoiesis."} {"id": "PMID:166527", "title": "[Oncocytes in a mixed canine mammary gland tumour].", "content": "The electronmicroscopic findings of a canine mixed mammary gland tumour containing oncocytes, are described. The tumour consists of small myxoid foci and glandular formations with an organoid structure. The glandular walls are composed of myoepithelial differentiated cells and epithelial cells. Most of the latter are oncocytes and characterized by an extensive amount of pathic mitochondria. The myxoid foci consist of myoepithelial differentiated cells.", "contents": "[Oncocytes in a mixed canine mammary gland tumour]. The electronmicroscopic findings of a canine mixed mammary gland tumour containing oncocytes, are described. The tumour consists of small myxoid foci and glandular formations with an organoid structure. The glandular walls are composed of myoepithelial differentiated cells and epithelial cells. Most of the latter are oncocytes and characterized by an extensive amount of pathic mitochondria. The myxoid foci consist of myoepithelial differentiated cells."} {"id": "PMID:166535", "title": "Inhibition of prolactin secretion by lergotrile mesylate: mechanism of action.", "content": "Lergotrile mesylate (2-chloro-6-methylergoline-8beta-acetonitrile, methane-sulphate salt) was shown to be a potent inhibitor of prolactin secretion in vivo and in vitro. The dopamine receptor blocker, pimozide, was able to reverse the inhibitory effect of lergotrile mesylate (LM) on prolactin release from rat pituitaries in vitro. Alpha-adrenergic or beta-adrenergic receptor blockers were unable to antogonize the action of LM on prolactin release. These findings indicate that ergolines such as LM inhibit prolactin release from pituitaries by activating an adenohypophyseal dopamine receptor. LM is currently undergoing clinical trial as a prolactin inhibitor and a dopamine agonist.", "contents": "Inhibition of prolactin secretion by lergotrile mesylate: mechanism of action. Lergotrile mesylate (2-chloro-6-methylergoline-8beta-acetonitrile, methane-sulphate salt) was shown to be a potent inhibitor of prolactin secretion in vivo and in vitro. The dopamine receptor blocker, pimozide, was able to reverse the inhibitory effect of lergotrile mesylate (LM) on prolactin release from rat pituitaries in vitro. Alpha-adrenergic or beta-adrenergic receptor blockers were unable to antogonize the action of LM on prolactin release. These findings indicate that ergolines such as LM inhibit prolactin release from pituitaries by activating an adenohypophyseal dopamine receptor. LM is currently undergoing clinical trial as a prolactin inhibitor and a dopamine agonist."} {"id": "PMID:166536", "title": "The ontogeny and regulation of corticosteroid secretion by the ovine foetal adrenal.", "content": "Adrenal glands of foetal sheep of 40 days gestation to term were incubated with and without ACTH or an increased [K-+]. With ACTH, the 40 day foetal adrenal was capable of producing more cortisol and aldosterone per g body weight than was the term adrenal. ACTH was a potent stimulus to aldosterone and cortisol production in foetuses aged 60-90 days, and this effect declined significantly in the 91-120 day period. An increased [K-+] was stimulatory to aldosterone production only after 120 days gestation. Peripheral blood levels of aldosterone, corticosterone, cortisol, 11-deoxycortisol and 11-deoxycorticosterone were measured in foetuses 60 days to term and the levels of aldosterone and cortisol were significantly lower in 90-120 day foetuses than in the younger or older ones. Direct adrenal vein cannulation proved all five steroids to be secretory products of the foetal adrenal.", "contents": "The ontogeny and regulation of corticosteroid secretion by the ovine foetal adrenal. Adrenal glands of foetal sheep of 40 days gestation to term were incubated with and without ACTH or an increased [K-+]. With ACTH, the 40 day foetal adrenal was capable of producing more cortisol and aldosterone per g body weight than was the term adrenal. ACTH was a potent stimulus to aldosterone and cortisol production in foetuses aged 60-90 days, and this effect declined significantly in the 91-120 day period. An increased [K-+] was stimulatory to aldosterone production only after 120 days gestation. Peripheral blood levels of aldosterone, corticosterone, cortisol, 11-deoxycortisol and 11-deoxycorticosterone were measured in foetuses 60 days to term and the levels of aldosterone and cortisol were significantly lower in 90-120 day foetuses than in the younger or older ones. Direct adrenal vein cannulation proved all five steroids to be secretory products of the foetal adrenal."} {"id": "PMID:166537", "title": "The influence of androgens on protein synthesis by cultured rat epididymal tubules.", "content": "Rat epididymal tubules maintained in organ culture for 3 days respond to the addition of androgens to the culture media (testosterone and dihydrotestosterone 1 x 10-minus 5 m and 1 x 10-minus 7 m) with an increased incorporation of amino acids into acid-insoluble material. Significant androgenic stimulation is observed only 24 h after addition of hormone, while an inhibitory effect is found at earlier periods. The stimulation seems to be specifically produced by androgens; it is blocked by cyproterone acetate and is not elicited by oestradiol-17beta or corticosterone. The process appears to involve RNA synthesis since actinomycin D suppresses the stimulatory effect of androgen. Evidence suggests that cAMP production is not a primordial step in the response to androgen since dibutyryl cAMP did not mimick the androgenic effect, theophylline did not potentiate the response and alpha,beta-methylene ATP, which competitively inhibits adenyl cyclase, failed to alter the androgenic effect. Radioactive testosterone and dihydrotestosterone added to the culture media showed a preferential intranuclear localization as well as extensive metabolism. DHT was found to be the principal intranuclear steroid.", "contents": "The influence of androgens on protein synthesis by cultured rat epididymal tubules. Rat epididymal tubules maintained in organ culture for 3 days respond to the addition of androgens to the culture media (testosterone and dihydrotestosterone 1 x 10-minus 5 m and 1 x 10-minus 7 m) with an increased incorporation of amino acids into acid-insoluble material. Significant androgenic stimulation is observed only 24 h after addition of hormone, while an inhibitory effect is found at earlier periods. The stimulation seems to be specifically produced by androgens; it is blocked by cyproterone acetate and is not elicited by oestradiol-17beta or corticosterone. The process appears to involve RNA synthesis since actinomycin D suppresses the stimulatory effect of androgen. Evidence suggests that cAMP production is not a primordial step in the response to androgen since dibutyryl cAMP did not mimick the androgenic effect, theophylline did not potentiate the response and alpha,beta-methylene ATP, which competitively inhibits adenyl cyclase, failed to alter the androgenic effect. Radioactive testosterone and dihydrotestosterone added to the culture media showed a preferential intranuclear localization as well as extensive metabolism. DHT was found to be the principal intranuclear steroid."} {"id": "PMID:166538", "title": "Growth in monolayer culture of rat pituitary cells which synthetize and release acth.", "content": "Cultures of rat pituitary gland cells were developed to study biosynthesis and release of ACTH. ACTH measurement was accomplished by radioimmunoassay. ACTH release was observed following stimulation with theophylline and cAMP in a dose-dependent manner. Biosynthesis was demonstrated by incorporation of 3-H-phenylalanine into the hormone, employing a double antibody technique.", "contents": "Growth in monolayer culture of rat pituitary cells which synthetize and release acth. Cultures of rat pituitary gland cells were developed to study biosynthesis and release of ACTH. ACTH measurement was accomplished by radioimmunoassay. ACTH release was observed following stimulation with theophylline and cAMP in a dose-dependent manner. Biosynthesis was demonstrated by incorporation of 3-H-phenylalanine into the hormone, employing a double antibody technique."} {"id": "PMID:166539", "title": "Effect of iodized oil on iodine content, thyroglobulin maturation and on biochemical constituents of endemic goitre in brazil.", "content": "The biochemical and morphological changes in thyroid glands were studied in 5 patients with endemic goitre in the region before and one year after the administration of iodized oil. Each patient received a tracer dose of 125-I 3-5 weeks before the biopsy and another tracer of 131-I 12 h before surgery. It was observed that: 1. Iodine deficient goitrous glands had more protein per gram of tissue and that this was corrected by iodination. 2. The goitrous glands exhibited a higher relative proportion of particulate iodoprotein that incorporates more labelled iodine in relation to time of labelling. This abnormal situation is reverted to normal by iodination. 3. A significantly higher proportion of T3 + T4 is synthetized by the glands treated with iodized oil. 4. The increased amount of 127-I per gram of tissue is followed by an increased iodination level of thyroglobulin. 5. The ultracentrifugal pattern of proteins observed for iodine deficient glands differed from the iodinated glands, indicating a failure of maturation of thyroglobulin and possibly a greater than normal degree of heterogeneity. 6. The shift in sedimentation pattern was clearly induced by the increased degree of iodination, as shown by the iodized oil injection. 7. The increased cellularity and the higher rate of protein synthesis in the goitrous glands are reverted to normal after the iodized oil injection.", "contents": "Effect of iodized oil on iodine content, thyroglobulin maturation and on biochemical constituents of endemic goitre in brazil. The biochemical and morphological changes in thyroid glands were studied in 5 patients with endemic goitre in the region before and one year after the administration of iodized oil. Each patient received a tracer dose of 125-I 3-5 weeks before the biopsy and another tracer of 131-I 12 h before surgery. It was observed that: 1. Iodine deficient goitrous glands had more protein per gram of tissue and that this was corrected by iodination. 2. The goitrous glands exhibited a higher relative proportion of particulate iodoprotein that incorporates more labelled iodine in relation to time of labelling. This abnormal situation is reverted to normal by iodination. 3. A significantly higher proportion of T3 + T4 is synthetized by the glands treated with iodized oil. 4. The increased amount of 127-I per gram of tissue is followed by an increased iodination level of thyroglobulin. 5. The ultracentrifugal pattern of proteins observed for iodine deficient glands differed from the iodinated glands, indicating a failure of maturation of thyroglobulin and possibly a greater than normal degree of heterogeneity. 6. The shift in sedimentation pattern was clearly induced by the increased degree of iodination, as shown by the iodized oil injection. 7. The increased cellularity and the higher rate of protein synthesis in the goitrous glands are reverted to normal after the iodized oil injection."} {"id": "PMID:166540", "title": "The excretion of individual adenocartical steroids during normal childhood and adolescence.", "content": "The excretion of 7 individual 17-oxosteroids and 7 individual corticosteroids in 24 h urine samples from 62 normal infants, children and adolescents, based on an accurate and specific paper chromatographic method for their separation and quantitation, is reported. The excretion of the 11-deoxy-17-oxosteroids gradually increases from 7 years of age and the increase becomes more rapid 2 or 3 years before the clinical signs of puberty appear. The rise continues throughout puberty and beyond it until the adult level is reached. The increase far exceeds that which would be accounted for by the growth of the individual. The increase in the excretion of the 11-oxy-17-oxosteroids with age is much more gradual. Androgens favour the formation of 5alpha metabolites and the 5alpha:5beta ratio of the total 5alpha 17-oxosteroids and the total 5beta 17-oxosteroids shows a statistically significant increase with age. In addition, a relatively high 5alpha:5beta ratio is noted in male infants, which is likely to be related to their relatively high plasma testosterone levels. The excretion of the 17-hydroxycorticosteroids and the alpha-ketolic metabolites of cortisol gradually rises with age and correlates with body weight. The alpha-ketolic metabolites of corticosterone are relatively high in infancy, but after the age of 4 years their excretion also correlates with body weight. An increase in the 5alpha:5beta ratio of allo-THF to THF is noted at puberty similar to that found with the 5alpha:5beta ratios of the 17-oxosteroids.", "contents": "The excretion of individual adenocartical steroids during normal childhood and adolescence. The excretion of 7 individual 17-oxosteroids and 7 individual corticosteroids in 24 h urine samples from 62 normal infants, children and adolescents, based on an accurate and specific paper chromatographic method for their separation and quantitation, is reported. The excretion of the 11-deoxy-17-oxosteroids gradually increases from 7 years of age and the increase becomes more rapid 2 or 3 years before the clinical signs of puberty appear. The rise continues throughout puberty and beyond it until the adult level is reached. The increase far exceeds that which would be accounted for by the growth of the individual. The increase in the excretion of the 11-oxy-17-oxosteroids with age is much more gradual. Androgens favour the formation of 5alpha metabolites and the 5alpha:5beta ratio of the total 5alpha 17-oxosteroids and the total 5beta 17-oxosteroids shows a statistically significant increase with age. In addition, a relatively high 5alpha:5beta ratio is noted in male infants, which is likely to be related to their relatively high plasma testosterone levels. The excretion of the 17-hydroxycorticosteroids and the alpha-ketolic metabolites of cortisol gradually rises with age and correlates with body weight. The alpha-ketolic metabolites of corticosterone are relatively high in infancy, but after the age of 4 years their excretion also correlates with body weight. An increase in the 5alpha:5beta ratio of allo-THF to THF is noted at puberty similar to that found with the 5alpha:5beta ratios of the 17-oxosteroids."} {"id": "PMID:166544", "title": "Histochemical data on the liver of the marmoset (Callithrix jacchus).", "content": "The histochemistry of the hepatic parenchymal cells was studied in four Callithrix jacchus. A large amount of glycogen was noted throughout the lobules while the UDPG-GT and the phosphorylases were found unevenly distributed by the hepatic strands with different degrees of reactivity. Near the central vein one of the livers showed PAS-positive nuclear corpuscles that were more conspicuous in the hepatic cells with a larger amount of cytoplasmic glycogen and weaker UDPG-GT and phosphorylase reactivities. G-6PA (in a larger amount) and LDH (in a moderate amount) were found evenly distributed in the hepatic strands. F-1-6PA was seen sometimes with a stronger reactivity at the peripheral part of the lobules. The enzymes of the pentose shunt (G-6PDH, 6-PGDH and NADPH-2-TR) reacted strongly and as a rule evenly distributed near the hepatic lobules. Occasionally they reacted more intensely in the row of hepatic cells disposed just around the central vein. Cytochrome oxidase showed a very faint reaction. Cis-aconitase and ICDH were weak or moderate. NADH-2-TR more than SDH more than MDH were seen frequently diffused near the hepatic strands. SDH and MDH in some instances showed a stronger reactivity in the row or group of hepatic cells around the central vein. ATPase at pH 6.3 was negative in the marmoset liver; ATPase at pH 7.4 was mainly found in the wall of the portal area vessels; ATPase at pH 8.5 showed a stronger reactivity in the cytoplasm of the hepatic cells and ATPase at pH 9.4 was more abundant in the bile capillaries. The reactivity of the lipid metabolism enzymes was moderate with regard to alpha-GPDH or negligible with regard to beta-OHBDH. Acid phosphatase showed a stronger reaction, but almost limited to the Kupffer cells. The hepatic cells showed only a moderate amount of RNA. Some enzymes of the protein metabolism, such as GDH and leucine aminopeptidase showed a stronger reactivity while some others, such as alanyl aminopeptidase and MAO, were seen diffused near the hepatic lobules in a small amount. Enzymes of the mucopolysaccharide metabolism were not found at all (beta-glucuronidase) or showed only a weak reactivity, such as xylitol dehydrogenase.", "contents": "Histochemical data on the liver of the marmoset (Callithrix jacchus). The histochemistry of the hepatic parenchymal cells was studied in four Callithrix jacchus. A large amount of glycogen was noted throughout the lobules while the UDPG-GT and the phosphorylases were found unevenly distributed by the hepatic strands with different degrees of reactivity. Near the central vein one of the livers showed PAS-positive nuclear corpuscles that were more conspicuous in the hepatic cells with a larger amount of cytoplasmic glycogen and weaker UDPG-GT and phosphorylase reactivities. G-6PA (in a larger amount) and LDH (in a moderate amount) were found evenly distributed in the hepatic strands. F-1-6PA was seen sometimes with a stronger reactivity at the peripheral part of the lobules. The enzymes of the pentose shunt (G-6PDH, 6-PGDH and NADPH-2-TR) reacted strongly and as a rule evenly distributed near the hepatic lobules. Occasionally they reacted more intensely in the row of hepatic cells disposed just around the central vein. Cytochrome oxidase showed a very faint reaction. Cis-aconitase and ICDH were weak or moderate. NADH-2-TR more than SDH more than MDH were seen frequently diffused near the hepatic strands. SDH and MDH in some instances showed a stronger reactivity in the row or group of hepatic cells around the central vein. ATPase at pH 6.3 was negative in the marmoset liver; ATPase at pH 7.4 was mainly found in the wall of the portal area vessels; ATPase at pH 8.5 showed a stronger reactivity in the cytoplasm of the hepatic cells and ATPase at pH 9.4 was more abundant in the bile capillaries. The reactivity of the lipid metabolism enzymes was moderate with regard to alpha-GPDH or negligible with regard to beta-OHBDH. Acid phosphatase showed a stronger reaction, but almost limited to the Kupffer cells. The hepatic cells showed only a moderate amount of RNA. Some enzymes of the protein metabolism, such as GDH and leucine aminopeptidase showed a stronger reactivity while some others, such as alanyl aminopeptidase and MAO, were seen diffused near the hepatic lobules in a small amount. Enzymes of the mucopolysaccharide metabolism were not found at all (beta-glucuronidase) or showed only a weak reactivity, such as xylitol dehydrogenase."} {"id": "PMID:166545", "title": "Unusual, rod-shaped cytoplasmic inclusions (Hirano bodies) in a cerebellar hemangioblastoma.", "content": "The present study reports unusual, long, tubular, rod-shaped cytoplasmic inclusions found in the stromal cells of a cerebellar hemangioblastoma, associated with von Hippel-Lindau syndrome. These inclusions have two layers of circular, laminated filaments, and longitudinally arranged filaments; and appear similar to the so-called \"Hirano bodies\", which have been previously found in normal and various pathologic conditions of the brain tissue, skeletal muscle cells in myopathy, and interstitial cells of the testis. A review of previous ultrastructural studies of cerebellar hemangioblastoma shows several different types of cytoplasmic inclusions, but none are found to be identical to the present report.", "contents": "Unusual, rod-shaped cytoplasmic inclusions (Hirano bodies) in a cerebellar hemangioblastoma. The present study reports unusual, long, tubular, rod-shaped cytoplasmic inclusions found in the stromal cells of a cerebellar hemangioblastoma, associated with von Hippel-Lindau syndrome. These inclusions have two layers of circular, laminated filaments, and longitudinally arranged filaments; and appear similar to the so-called \"Hirano bodies\", which have been previously found in normal and various pathologic conditions of the brain tissue, skeletal muscle cells in myopathy, and interstitial cells of the testis. A review of previous ultrastructural studies of cerebellar hemangioblastoma shows several different types of cytoplasmic inclusions, but none are found to be identical to the present report."} {"id": "PMID:166546", "title": "Intra-axonal Corpora amylacea in ventral and lateral horns of the spinal cord.", "content": "Deposits similar to corpora amylacea were observed by electron microscopy and light microscopy within thin myelinated axons in the spinal gray matter in various diseases. By electron microscopy the deposits consisted of randomly interlacing short linear structures of various thickness which were different from tangles of neurofilaments. Sometimes they contained dense granules and electron-dense floccules. Though their incidence was relatively high in some cases of degenerative or metabolic disease of the central nervous system, they were not specific to any disease but seemed to be related to aging, indicating a peculiar aspect of chronic degeneration of the axons.", "contents": "Intra-axonal Corpora amylacea in ventral and lateral horns of the spinal cord. Deposits similar to corpora amylacea were observed by electron microscopy and light microscopy within thin myelinated axons in the spinal gray matter in various diseases. By electron microscopy the deposits consisted of randomly interlacing short linear structures of various thickness which were different from tangles of neurofilaments. Sometimes they contained dense granules and electron-dense floccules. Though their incidence was relatively high in some cases of degenerative or metabolic disease of the central nervous system, they were not specific to any disease but seemed to be related to aging, indicating a peculiar aspect of chronic degeneration of the axons."} {"id": "PMID:166547", "title": "A study on the influence of papovavirus upon encephalitis caused by SSPE agent.", "content": "To investigate a possible interaction between the SSPE agent and papovaviruses, histopathological and statistical evaluations were made of encephalitis induced in hamsters by intracerberal inoculation with isolates from SSPE and PML patients, and with BK virus, alone or in combination. With SSPE virus alone, hamster brains showed a reduction of susceptibility to encephalitis with increasing age. A modification of the pathology of SSPE encephalitis was observed after administration of the PML isolate or BK virus: encephalitis was either enhanced or inhibited depending on the time the papovaviruses were administered. A possible mechanism of interaction between SSPE and papovaviruses is briefly discussed.", "contents": "A study on the influence of papovavirus upon encephalitis caused by SSPE agent. To investigate a possible interaction between the SSPE agent and papovaviruses, histopathological and statistical evaluations were made of encephalitis induced in hamsters by intracerberal inoculation with isolates from SSPE and PML patients, and with BK virus, alone or in combination. With SSPE virus alone, hamster brains showed a reduction of susceptibility to encephalitis with increasing age. A modification of the pathology of SSPE encephalitis was observed after administration of the PML isolate or BK virus: encephalitis was either enhanced or inhibited depending on the time the papovaviruses were administered. A possible mechanism of interaction between SSPE and papovaviruses is briefly discussed."} {"id": "PMID:166548", "title": "Studies in cholestasis of pregnancy.", "content": "Forty-one pregnant women with pruritus, in whom cholestasis was verified by the presence in their serum of an abnormal lipoprotein, lipoprotein-X (LP-X), were divided into two clinical groups, pruritus gravidarum (PG) (n=20) and hepatosis of pregnancy (HP) (n=21) in relation to serum bilirubin (below and above 1.2 mg/100 ml, respectively) and/or SGOT, SGPT (below and above 50 units/l, respectively). In HP, but not in PG, serum lipids, i.e. cholesterol, phospholipids, triglycerides, pre-beta-lipoproteins (very-low-density lipoproteins), and low-density lipoproteins were increased and high-density lipoproteins decreased when compared with suitable controls. Serum lipids were elevated in proportion to the derangement in the liver function tests, alkaline phosphatase, SGOT, and SGPT. The occurrence of LP-X was inversely related to HDL cholesterol, suggesting a causal relationship between HDL lipid metabolism and the presence of LP-X. Serum TIBC, Simplastin A, and serum iron were elevated in HP in relation to the degree of deterioration of liver function tests. Some of these changes in serum in cholestatic pregnancy may partially (serum triglycerides and pre-beta-lipoproteins) or completely (TIBC and Simplastin A) be explained by an enhanced estrogen influence in promoting increased liver lipid/protein metabolism.", "contents": "Studies in cholestasis of pregnancy. Forty-one pregnant women with pruritus, in whom cholestasis was verified by the presence in their serum of an abnormal lipoprotein, lipoprotein-X (LP-X), were divided into two clinical groups, pruritus gravidarum (PG) (n=20) and hepatosis of pregnancy (HP) (n=21) in relation to serum bilirubin (below and above 1.2 mg/100 ml, respectively) and/or SGOT, SGPT (below and above 50 units/l, respectively). In HP, but not in PG, serum lipids, i.e. cholesterol, phospholipids, triglycerides, pre-beta-lipoproteins (very-low-density lipoproteins), and low-density lipoproteins were increased and high-density lipoproteins decreased when compared with suitable controls. Serum lipids were elevated in proportion to the derangement in the liver function tests, alkaline phosphatase, SGOT, and SGPT. The occurrence of LP-X was inversely related to HDL cholesterol, suggesting a causal relationship between HDL lipid metabolism and the presence of LP-X. Serum TIBC, Simplastin A, and serum iron were elevated in HP in relation to the degree of deterioration of liver function tests. Some of these changes in serum in cholestatic pregnancy may partially (serum triglycerides and pre-beta-lipoproteins) or completely (TIBC and Simplastin A) be explained by an enhanced estrogen influence in promoting increased liver lipid/protein metabolism."} {"id": "PMID:166549", "title": "Immunohistochemical demonstration of chorionic gonadotrophin in trophoblastic tumors.", "content": "Chorionic gonadotrophin has immunohistochemically been localized to trophoblastic tissue. In normal placenta immunoreactivity was found in syncytiotrophoblastic cells. However, in trophoblastic neoplasms, chorioadenoma destruens and choriocarcinoma, the hormone was also found in cytotrophoblastic cells. The tumor cells showing immunoreactivity appeared to have distinct light microscopic features.", "contents": "Immunohistochemical demonstration of chorionic gonadotrophin in trophoblastic tumors. Chorionic gonadotrophin has immunohistochemically been localized to trophoblastic tissue. In normal placenta immunoreactivity was found in syncytiotrophoblastic cells. However, in trophoblastic neoplasms, chorioadenoma destruens and choriocarcinoma, the hormone was also found in cytotrophoblastic cells. The tumor cells showing immunoreactivity appeared to have distinct light microscopic features."} {"id": "PMID:166552", "title": "Histological changes in the submandibular glands of rats after intraductal injection of chemical carcinogens.", "content": "Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and \"benign lymphoepithelial lesion\"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called \"mixed tumor\"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called \"mixed tumor\"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign \"lymphoepithelial lesion\"-like pattern.", "contents": "Histological changes in the submandibular glands of rats after intraductal injection of chemical carcinogens. Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and \"benign lymphoepithelial lesion\"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called \"mixed tumor\"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called \"mixed tumor\"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign \"lymphoepithelial lesion\"-like pattern."} {"id": "PMID:166553", "title": "Mechanism of the formation of megamitochondria induced by copper-chelating agents. II. Isolation and some properties of megamitochondria from the cuprizone-treated mouse liver.", "content": "Megamitochondria have been isolated from the liver of the cuprizone-fed mouse with the aid of bovine serum albumin. Phosphorylating capacities of megamitochondria, specified above, in terms of respiratory control ratios and ADP/O ratios have revealed that they are not uncoupled completely. Biochemical properties of megamitochondria which are related to the metabolism of copper have shown that copper-chelating action of cuprizone may not be directly related to the formation of megamitochondria in vivo. Namely, cytochrome contents, activities of cytochrome oxidase and monoamine oxidase and contents of copper of megamitochondria were unchanged compared with those of the control. However, contents of divalent metals such as Ca-++ and Mg-++, especially that of the former, in megamitochondria decreased significantly. It is suggested that cuprizone may alter Mg-++/Ca-++ ratios when it is administered in vivo, and that changes in the ratio might play a key role in the formation of megamitochondria.", "contents": "Mechanism of the formation of megamitochondria induced by copper-chelating agents. II. Isolation and some properties of megamitochondria from the cuprizone-treated mouse liver. Megamitochondria have been isolated from the liver of the cuprizone-fed mouse with the aid of bovine serum albumin. Phosphorylating capacities of megamitochondria, specified above, in terms of respiratory control ratios and ADP/O ratios have revealed that they are not uncoupled completely. Biochemical properties of megamitochondria which are related to the metabolism of copper have shown that copper-chelating action of cuprizone may not be directly related to the formation of megamitochondria in vivo. Namely, cytochrome contents, activities of cytochrome oxidase and monoamine oxidase and contents of copper of megamitochondria were unchanged compared with those of the control. However, contents of divalent metals such as Ca-++ and Mg-++, especially that of the former, in megamitochondria decreased significantly. It is suggested that cuprizone may alter Mg-++/Ca-++ ratios when it is administered in vivo, and that changes in the ratio might play a key role in the formation of megamitochondria."} {"id": "PMID:166550", "title": "Meni\u00e9re's disease. Electron microscopy of the vestibular ganglion and end organs after ultrasound.", "content": "Material for electron microscopy study was obtained from a patient previously suffering from Meniere's disease and treated by ultrasound. It consisted of parts of the membranous labyrinth as well as the vestibular ganglion. The neuro-epithelium of the macula showed degenerative changes and there was marked vacuolation of the cytoplasm. The endothelial cells lining the semicircular canal showed gross vacuoles contained degenerating mitochondria and some debris which may reach the endolymph. The wall of the semi circular canal was oedematous and the basement membrane lifted off by oedematous fluid. There was obvious change in nerves and neurones. The nerves showed loosening of the myelin sheath and ballooning. The neurones contained lipoid inclusions and multicystic lysosomes. Similar inclusions were also noted in some myelinated nerves.", "contents": "Meni\u00e9re's disease. Electron microscopy of the vestibular ganglion and end organs after ultrasound. Material for electron microscopy study was obtained from a patient previously suffering from Meniere's disease and treated by ultrasound. It consisted of parts of the membranous labyrinth as well as the vestibular ganglion. The neuro-epithelium of the macula showed degenerative changes and there was marked vacuolation of the cytoplasm. The endothelial cells lining the semicircular canal showed gross vacuoles contained degenerating mitochondria and some debris which may reach the endolymph. The wall of the semi circular canal was oedematous and the basement membrane lifted off by oedematous fluid. There was obvious change in nerves and neurones. The nerves showed loosening of the myelin sheath and ballooning. The neurones contained lipoid inclusions and multicystic lysosomes. Similar inclusions were also noted in some myelinated nerves."} {"id": "PMID:166554", "title": "Immunofluorescent demonstration of plasma protein entry into arterial wall by cholesterol, epinephrine, norepinephrine and angiotensin II.", "content": "Thepresence of IgG and beta-lipoprotein in thoracic and abdominal aortas of 33 rhesus monkeys under various conditions was observed by immunofluorescence and interference filter technique. In untreated and placebo control monkeys, a definite fluorescence due to IgG was seen in highly limited areas of the subendothelial space and the innermost layers and a weak but positive fluorescence due to beta-lipoprotein was sometimes show in highly limited spots of the subendothelial space, but not the medial layers. In challenged animals with cholesterol (1 g/kg p.o.) or epinephrine (1 mug/kg i.v.) or norepinephrine (10 mug/kg i.v.) or angiotensin II (1 mug/kg i.v.) or cholesterol (1 g/kg p.o.) plus epinephrine (1 mug/kg i.v.), definite fluorescence showing the entry of beta-lipoprotein and IgG from the vessel lumen into the subendothelial space and then into the medial layers of the arterial wall was clearly shown by serial sacrificing of animals after each challenge. The passage of beta-lipoprotein through the internal elastic lamina into the medial layer, was characteristically delayed as compared with that of IgG. In pretreated animals with pyridinolcarbamate (PDC) (10 mg/kg p.o.), EG467 (1 mg/kg p.o.) and Premarin (5 mg/kg i.v.), the acute entry of those plasma proteins was significantly inhibited.", "contents": "Immunofluorescent demonstration of plasma protein entry into arterial wall by cholesterol, epinephrine, norepinephrine and angiotensin II. Thepresence of IgG and beta-lipoprotein in thoracic and abdominal aortas of 33 rhesus monkeys under various conditions was observed by immunofluorescence and interference filter technique. In untreated and placebo control monkeys, a definite fluorescence due to IgG was seen in highly limited areas of the subendothelial space and the innermost layers and a weak but positive fluorescence due to beta-lipoprotein was sometimes show in highly limited spots of the subendothelial space, but not the medial layers. In challenged animals with cholesterol (1 g/kg p.o.) or epinephrine (1 mug/kg i.v.) or norepinephrine (10 mug/kg i.v.) or angiotensin II (1 mug/kg i.v.) or cholesterol (1 g/kg p.o.) plus epinephrine (1 mug/kg i.v.), definite fluorescence showing the entry of beta-lipoprotein and IgG from the vessel lumen into the subendothelial space and then into the medial layers of the arterial wall was clearly shown by serial sacrificing of animals after each challenge. The passage of beta-lipoprotein through the internal elastic lamina into the medial layer, was characteristically delayed as compared with that of IgG. In pretreated animals with pyridinolcarbamate (PDC) (10 mg/kg p.o.), EG467 (1 mg/kg p.o.) and Premarin (5 mg/kg i.v.), the acute entry of those plasma proteins was significantly inhibited."} {"id": "PMID:166551", "title": "[Endocrinologic evidence for differential diagnosis and follow-up of expanding intraseller processes].", "content": "In expectance of early chromophobic adenomata the transsphenoidal intervention revealed in 5 cases cerebrospinal fluid only, 3 times in closed cysts, 2 times with connection to the endocranial space. In one case the neuro-surgical approach revealed basal arachnoidal cysts. Endocrine studies detected no significant differences between empty sella patients and chromophobic adenomata. Compared with this in suspected acromegalia, the measurement of the different functions of the pituitary gland and especially the repeated control of somatropin proved most effective for early diagnosis, control of the operative effect and long-term success or failure.", "contents": "[Endocrinologic evidence for differential diagnosis and follow-up of expanding intraseller processes]. In expectance of early chromophobic adenomata the transsphenoidal intervention revealed in 5 cases cerebrospinal fluid only, 3 times in closed cysts, 2 times with connection to the endocranial space. In one case the neuro-surgical approach revealed basal arachnoidal cysts. Endocrine studies detected no significant differences between empty sella patients and chromophobic adenomata. Compared with this in suspected acromegalia, the measurement of the different functions of the pituitary gland and especially the repeated control of somatropin proved most effective for early diagnosis, control of the operative effect and long-term success or failure."} {"id": "PMID:166555", "title": "Phagocytosis of lymphoblastoid cells and cell destruction of human malignant tumor cells.", "content": "On the basis of the previous study, on the cell interaction between malignant tumor cells and other cells, especially with lymphocytes, the present study was carried out by investigating cell to cell interaction of human malignant tumor cells and human lymphoblastoid cells such as T-cell (MOLT-4 cell) and B-cell (Burkitt lymphoma cell). As a result it has been revealed that live lymphoblastoid cells were not adhered on the cell surface of the tumor cells, nor is it ingested by tumor cells, but in thepresence of HVJ (Sendai virus: 2,000 H.A. units) it adheres slightly on the cell surface of tumor cell but no cell fusion of tumor cells and lymphoblastoid cells is observable. On the other hand, the tumor cell as well as T-cell and B-cell all have receptors to concanavalin A (Con. A) on their cell surfaces, and they show a marked cell binding such as tumor cell and T-cell, tumor cell and B-cell, and there can be observed a marked phagocytosis of lymphoblastoid cells by tumor cells. Moreover, the tumor cells that have phagocytized lymphoblastoid cells undergo a marked cell destruction within 4 hours of cell-binding and phagocytosis, which is especially prominent in the case of phagocytosis of E.B cell by tumor cell.", "contents": "Phagocytosis of lymphoblastoid cells and cell destruction of human malignant tumor cells. On the basis of the previous study, on the cell interaction between malignant tumor cells and other cells, especially with lymphocytes, the present study was carried out by investigating cell to cell interaction of human malignant tumor cells and human lymphoblastoid cells such as T-cell (MOLT-4 cell) and B-cell (Burkitt lymphoma cell). As a result it has been revealed that live lymphoblastoid cells were not adhered on the cell surface of the tumor cells, nor is it ingested by tumor cells, but in thepresence of HVJ (Sendai virus: 2,000 H.A. units) it adheres slightly on the cell surface of tumor cell but no cell fusion of tumor cells and lymphoblastoid cells is observable. On the other hand, the tumor cell as well as T-cell and B-cell all have receptors to concanavalin A (Con. A) on their cell surfaces, and they show a marked cell binding such as tumor cell and T-cell, tumor cell and B-cell, and there can be observed a marked phagocytosis of lymphoblastoid cells by tumor cells. Moreover, the tumor cells that have phagocytized lymphoblastoid cells undergo a marked cell destruction within 4 hours of cell-binding and phagocytosis, which is especially prominent in the case of phagocytosis of E.B cell by tumor cell."} {"id": "PMID:166557", "title": "Dynamics of alpha-adrenergic inhibition of the adenyl cyclase-cyclic amp system in human adipose tissue.", "content": "In short-term incubations of fat cells isolated from human adipose tissue, noradrenaline (0.2-2x10--5 M), a mixed alpha and beta-adrenergic agonist, stimulated only slightly cyclic AMP accumulation. In the presence of the alpha-adrenergic blocking agent phentolamine (0.05-5mug/ml), noradrenaline markedly augmented the amount of labelled cyclic nucleotide. The stiumlatory effect of noradrenaline and noradrenaline plus phentolamine was abolished by propranolol (0.1-10 mug/ml). Theophylline (10--4-10--3 M) slightly increased the (3-H) cyclic AMP levels per se and magnified the stiumulatory action of other agents, but did not mimic the potentiating effect of phentolamine on noradrenaline action.", "contents": "Dynamics of alpha-adrenergic inhibition of the adenyl cyclase-cyclic amp system in human adipose tissue. In short-term incubations of fat cells isolated from human adipose tissue, noradrenaline (0.2-2x10--5 M), a mixed alpha and beta-adrenergic agonist, stimulated only slightly cyclic AMP accumulation. In the presence of the alpha-adrenergic blocking agent phentolamine (0.05-5mug/ml), noradrenaline markedly augmented the amount of labelled cyclic nucleotide. The stiumlatory effect of noradrenaline and noradrenaline plus phentolamine was abolished by propranolol (0.1-10 mug/ml). Theophylline (10--4-10--3 M) slightly increased the (3-H) cyclic AMP levels per se and magnified the stiumulatory action of other agents, but did not mimic the potentiating effect of phentolamine on noradrenaline action."} {"id": "PMID:166559", "title": "Subacute and acute endocarditis due to Pseudomonas cepacia in heroin addicts.", "content": "Five heroin addicts were treated for endocarditis caused by Pseudomonas cepacia. Two of these infections occurred in patients with no known heart disease whereas the others occurred at sites of previous endocarditis or valve prostheses. Infection was indolent in four patients but was associated with shock and skin lesions suggestive of ecthyma gangrenosum in the fifth. After failure of chloramphenicol and kanamycin, all patients were treated with a combination of sulfamethoxazole, trimethoprim and polymyxin plus heart valve resection or replacement.", "contents": "Subacute and acute endocarditis due to Pseudomonas cepacia in heroin addicts. Five heroin addicts were treated for endocarditis caused by Pseudomonas cepacia. Two of these infections occurred in patients with no known heart disease whereas the others occurred at sites of previous endocarditis or valve prostheses. Infection was indolent in four patients but was associated with shock and skin lesions suggestive of ecthyma gangrenosum in the fifth. After failure of chloramphenicol and kanamycin, all patients were treated with a combination of sulfamethoxazole, trimethoprim and polymyxin plus heart valve resection or replacement."} {"id": "PMID:166560", "title": "Epibulbar tumors in childhood.", "content": "Three hundred two cases of epibulbar tumors in children were retrospectively reviewed histologically and examined by diagnostic categories over a 49-year period. Of the 302 cases, 33% were choristomas; 29% nevi; 11%, epithelial inclusion cysts; 7%, papillomas; 6%, pyogenic granulomas; and 5% granulomas. Three cases of sqamous-cell carcinoma and one of rhabdomyosarcoma occurred as well as a variety of benign lesions.", "contents": "Epibulbar tumors in childhood. Three hundred two cases of epibulbar tumors in children were retrospectively reviewed histologically and examined by diagnostic categories over a 49-year period. Of the 302 cases, 33% were choristomas; 29% nevi; 11%, epithelial inclusion cysts; 7%, papillomas; 6%, pyogenic granulomas; and 5% granulomas. Three cases of sqamous-cell carcinoma and one of rhabdomyosarcoma occurred as well as a variety of benign lesions."} {"id": "PMID:166561", "title": "Proflavine photodynamic viral inactivation in herpes simplex keratitis.", "content": "We used the photodynamic inactivation technique with proflavine as the photoactive dye to treat herpetic epithelial keratitis in a preliminary study of patients who had idoxuridine toxicity or resistance. A comparative study with idoxuridine in treating dendritic ulcerations of the cornea showed a good therapeutic effect. But the investigation was suspended when adverse reactions, consisting of a generalized epithelial keratitis and an anterior uveitis, possibly of phototoxic origin, developed in a few patients receiving treatment. The ulcers treated by photodynamic inactivation apparently healed by a process of \"debridement\" followed by subsequent re-epithelialization.", "contents": "Proflavine photodynamic viral inactivation in herpes simplex keratitis. We used the photodynamic inactivation technique with proflavine as the photoactive dye to treat herpetic epithelial keratitis in a preliminary study of patients who had idoxuridine toxicity or resistance. A comparative study with idoxuridine in treating dendritic ulcerations of the cornea showed a good therapeutic effect. But the investigation was suspended when adverse reactions, consisting of a generalized epithelial keratitis and an anterior uveitis, possibly of phototoxic origin, developed in a few patients receiving treatment. The ulcers treated by photodynamic inactivation apparently healed by a process of \"debridement\" followed by subsequent re-epithelialization."} {"id": "PMID:166562", "title": "Immunologic protection of rabbit corneal allografts with heterologous blocking antibody.", "content": "We performed exchange penetrating keratoplasties in New Zealand White rabbits by using corneas soaked in heterologous \"blocking\" antibody (guinea pig antirabbit lymphocyte globulin) under various experimental situations and immunogenic stimuli. Results suggested that the antibody can protect the corneal graft from a weak rejection response possibility by blocking the afferent are of the immunologic rejection reflex, but cannot protect a graft subject to a strong immunologic rejection episode. Based on these results, the use of a blocking antibody in human transplantation would be of potential benefit and offer little risk to a graft recipient.", "contents": "Immunologic protection of rabbit corneal allografts with heterologous blocking antibody. We performed exchange penetrating keratoplasties in New Zealand White rabbits by using corneas soaked in heterologous \"blocking\" antibody (guinea pig antirabbit lymphocyte globulin) under various experimental situations and immunogenic stimuli. Results suggested that the antibody can protect the corneal graft from a weak rejection response possibility by blocking the afferent are of the immunologic rejection reflex, but cannot protect a graft subject to a strong immunologic rejection episode. Based on these results, the use of a blocking antibody in human transplantation would be of potential benefit and offer little risk to a graft recipient."} {"id": "PMID:166563", "title": "Experimentally induced malakoplakia.", "content": "Malakoplakia was induced experimentally by introducing large amounts of crude endotoxin-antigen comples of 075 Escherichia coli (E. coli 12797 CDC 0 group 75) into the kidneys and testes of rats. First leukocytes, then granulation tissue composed mainly of characteristic macrophages, the so-called Hansemann cells, appeared around the endotoxin-antigen mass. On the eighth day following the injection, deposition of calcium phosphate into the cytosegresomes of macrophages began and acused the formation of the Michaelis-Gutmann bodies necessary for the diagnosis of malakoplakia. The induction of the same process in humans by E coli endotoxin seems to be possible.", "contents": "Experimentally induced malakoplakia. Malakoplakia was induced experimentally by introducing large amounts of crude endotoxin-antigen comples of 075 Escherichia coli (E. coli 12797 CDC 0 group 75) into the kidneys and testes of rats. First leukocytes, then granulation tissue composed mainly of characteristic macrophages, the so-called Hansemann cells, appeared around the endotoxin-antigen mass. On the eighth day following the injection, deposition of calcium phosphate into the cytosegresomes of macrophages began and acused the formation of the Michaelis-Gutmann bodies necessary for the diagnosis of malakoplakia. The induction of the same process in humans by E coli endotoxin seems to be possible."} {"id": "PMID:166564", "title": "Lymphoid cell necrosis, thymic atrophy, and growth retardation in newborn mice inoculated with murine cytomegalovirus.", "content": "During studies on the effect of murine cytomegalovirus on the developing retina, virus was inoculated into the eyes of newborn Swiss mice, and the animals were sacrificed at various times thereafter. Controls consisted of mice inoculated with ultraviolet-inactivated murine cytomegalovirus and uninjected mice. Marked lymphoid cell necrosis, thymic atrophy, pronounced growth retardation, bacteremia, and death occurred in the animals inoculated with live virus. this virus-induced injury resulted in a marked depletion of lymphocytes in the subcapsular and cortical areas of the thymus as well as in the spleen, lymph nodes, and Peyer's patches. Areas of necrosis with viral inclusions were present at the site of inoculation and in various other organs including the spleen and bone marrow. Since growth retardation has been associated with thymic atrophy due to other causes, the observed abnormal physical development in the present study was interpreted as a sequel to the thymic injury. An implication of this study is that some human infants with concomitant immune deficiency and viral infection may have a primary viral disease with resultant secondary lymphoid tissue alterations, rather than a thymic disorder with a subsequent viral infection.", "contents": "Lymphoid cell necrosis, thymic atrophy, and growth retardation in newborn mice inoculated with murine cytomegalovirus. During studies on the effect of murine cytomegalovirus on the developing retina, virus was inoculated into the eyes of newborn Swiss mice, and the animals were sacrificed at various times thereafter. Controls consisted of mice inoculated with ultraviolet-inactivated murine cytomegalovirus and uninjected mice. Marked lymphoid cell necrosis, thymic atrophy, pronounced growth retardation, bacteremia, and death occurred in the animals inoculated with live virus. this virus-induced injury resulted in a marked depletion of lymphocytes in the subcapsular and cortical areas of the thymus as well as in the spleen, lymph nodes, and Peyer's patches. Areas of necrosis with viral inclusions were present at the site of inoculation and in various other organs including the spleen and bone marrow. Since growth retardation has been associated with thymic atrophy due to other causes, the observed abnormal physical development in the present study was interpreted as a sequel to the thymic injury. An implication of this study is that some human infants with concomitant immune deficiency and viral infection may have a primary viral disease with resultant secondary lymphoid tissue alterations, rather than a thymic disorder with a subsequent viral infection."} {"id": "PMID:166565", "title": "Ribosome-lamella complexes in neoplastic hematopoietic cells.", "content": "The ultrastructural cellular inclusions referred to as ribosome-lamella complexes were observed in the neoplastic cell population of 4 patients with three types of hematopoietic malignancy, monoblastic leukemia. Waldenstrom's macroglobulinemia, and chronic lymphatic leukemia. The ultrastructural characteristics of the inclusions were similar in the 4 cases. The percentage of cells affected ranged from approximately 90% in 1 patient with monoblastic leukemia to approximately 10% in a patient with Waldenstrom's macroglobulinemia. The complexes appeared to originate from the rough endoplasmic reticulum. Observations suggested a developmental sequence beginning with aggregate strands of rough endoplasmic reticulum, subsequent alignment of the strands of rough endoplasmic reticulum in a concentric configuration, followed by maturation to fully developed ribosome-lamella complexes. Although the ribosome-lamella complex has been found in the neoplastic cells of several patients with leukemic reticuloendotheliosis (\"hairy cell leukemia\"), its occurrence in these three different hematopoietic disorders indicates a lack of diagnostic specificity of this structure.", "contents": "Ribosome-lamella complexes in neoplastic hematopoietic cells. The ultrastructural cellular inclusions referred to as ribosome-lamella complexes were observed in the neoplastic cell population of 4 patients with three types of hematopoietic malignancy, monoblastic leukemia. Waldenstrom's macroglobulinemia, and chronic lymphatic leukemia. The ultrastructural characteristics of the inclusions were similar in the 4 cases. The percentage of cells affected ranged from approximately 90% in 1 patient with monoblastic leukemia to approximately 10% in a patient with Waldenstrom's macroglobulinemia. The complexes appeared to originate from the rough endoplasmic reticulum. Observations suggested a developmental sequence beginning with aggregate strands of rough endoplasmic reticulum, subsequent alignment of the strands of rough endoplasmic reticulum in a concentric configuration, followed by maturation to fully developed ribosome-lamella complexes. Although the ribosome-lamella complex has been found in the neoplastic cells of several patients with leukemic reticuloendotheliosis (\"hairy cell leukemia\"), its occurrence in these three different hematopoietic disorders indicates a lack of diagnostic specificity of this structure."} {"id": "PMID:166579", "title": "Idiopathic acquired cold urticaria in North India.", "content": "Forty-three otherwise healthy patients mostly between the ages of 10 and 40 were seen in North India during a two-year period with urticaria which developed on taking a cold water bath, exposure to cold winds, evaporation of rain water or sweat in that order of frequency. There was no familial predisposition to cold urticaria or atopic disorders. The refrigeration test for cryo-proteins was negative. Only one patient developed a wheal on contact with ice but 38 of 43 patients showed an exaggerated erythema response to a cold-pressure test (cryo-stimulation test).", "contents": "Idiopathic acquired cold urticaria in North India. Forty-three otherwise healthy patients mostly between the ages of 10 and 40 were seen in North India during a two-year period with urticaria which developed on taking a cold water bath, exposure to cold winds, evaporation of rain water or sweat in that order of frequency. There was no familial predisposition to cold urticaria or atopic disorders. The refrigeration test for cryo-proteins was negative. Only one patient developed a wheal on contact with ice but 38 of 43 patients showed an exaggerated erythema response to a cold-pressure test (cryo-stimulation test)."} {"id": "PMID:166580", "title": "Ultrastructural characteristics of canine transmissible venereal tumor at various stages of growth and regression.", "content": "Ultrastructural study of canine transmissible tumors in developing, mature, and regressing stages from 6 dogs revealed the presence of healthy and degenerating tumor cells in all neoplasms. The total number of neoplastic cells seemed to decrease, and the number of degenerating neoplastic cells seemed to increase in mature tumors. Macrophages, lymphocytes, and plasma cells infiltrated mature and regressing tumors. Alteratons in degenerating tumor cells consisted mainly of cytoplasmic changes in early stages and of both nuclear and cytoplasmic changes in cells in which degeneration was more advanced. Amounts of endoplasmic reticulum and ribosomes were decreased. There were swelling and vacuolation of mitochondria. Nuclear chromatin was clumped along the nuclear envelope, and the perinuclear space was widened. Degenerating cells often contained membrane-bound granules and clusters. Lamellar complexes were observed in tumor cells from 2 dogs. Virus particles were not seen.", "contents": "Ultrastructural characteristics of canine transmissible venereal tumor at various stages of growth and regression. Ultrastructural study of canine transmissible tumors in developing, mature, and regressing stages from 6 dogs revealed the presence of healthy and degenerating tumor cells in all neoplasms. The total number of neoplastic cells seemed to decrease, and the number of degenerating neoplastic cells seemed to increase in mature tumors. Macrophages, lymphocytes, and plasma cells infiltrated mature and regressing tumors. Alteratons in degenerating tumor cells consisted mainly of cytoplasmic changes in early stages and of both nuclear and cytoplasmic changes in cells in which degeneration was more advanced. Amounts of endoplasmic reticulum and ribosomes were decreased. There were swelling and vacuolation of mitochondria. Nuclear chromatin was clumped along the nuclear envelope, and the perinuclear space was widened. Degenerating cells often contained membrane-bound granules and clusters. Lamellar complexes were observed in tumor cells from 2 dogs. Virus particles were not seen."} {"id": "PMID:166581", "title": "A case of alveolar cell carcinoma accompanied by fluid and electrolyte depletion through production of voluminous amounts of lung liquids.", "content": "A patient is described who showed typical features of alveolar cell carcinoma, including production of a huge amount of clear frothy lung liquid (as much as 4 liter per day), diffuse dissemination of nodular lesions throughout the lung, and tall columnar cell proliferation outlining the alveolar walls uniformly without architectural destruction in the terminal lung unit. From the results of comparative serial analyses of biochemical components in the liquid and the serum, it is suggested that the excessive liquid production in this case should be due to abnormal secretory functioning of diffusely proliferated carcinoma cells.", "contents": "A case of alveolar cell carcinoma accompanied by fluid and electrolyte depletion through production of voluminous amounts of lung liquids. A patient is described who showed typical features of alveolar cell carcinoma, including production of a huge amount of clear frothy lung liquid (as much as 4 liter per day), diffuse dissemination of nodular lesions throughout the lung, and tall columnar cell proliferation outlining the alveolar walls uniformly without architectural destruction in the terminal lung unit. From the results of comparative serial analyses of biochemical components in the liquid and the serum, it is suggested that the excessive liquid production in this case should be due to abnormal secretory functioning of diffusely proliferated carcinoma cells."} {"id": "PMID:166582", "title": "Alpha1-antitrypsin deficiency and hepatic carcinoma.", "content": "A patient with homozygous ZZ alpha1-antitrypsin deficiency and severe pulmonary emphysema was discovered to have a mixed hepatocellular and cholangiolar hepatic carcinoma arising in a noncirrhotic liver. Because of the increasing frequency of hepatomas in patients with alpha1-antitrypsin deficiency, it is suggested that a causal relationship may exist.", "contents": "Alpha1-antitrypsin deficiency and hepatic carcinoma. A patient with homozygous ZZ alpha1-antitrypsin deficiency and severe pulmonary emphysema was discovered to have a mixed hepatocellular and cholangiolar hepatic carcinoma arising in a noncirrhotic liver. Because of the increasing frequency of hepatomas in patients with alpha1-antitrypsin deficiency, it is suggested that a causal relationship may exist."} {"id": "PMID:166584", "title": "Savings from generic prescriptions. A study of 33 pharmacies in Rochester, New York.", "content": "Brand name and gereric prescriptions for 12 drugs were surveyed at 33 pharmacies in the Rochester, New York, area to determine how frequently generic prescriptions were filled with a product other than the major brand, and at a savings to the consumer. Generic prescriptions for ampicillin, erythromycin, propoxyphene, and dioctyl sodium sulfosuccinate were often filled at prices lower than comparable brand name prescriptions. Occasional, but often substantial, savings were obtained for papaverine, pentaerythritol tetranitrate, and conjugated estrogens. No savings were obtained for penicillin V, chlorpheniramine, diphenylhydantoin, sulfisoxazole, or methenamine mandelate. The pharmacists included in the survey identified correctly a mean of 18.5 out of 22 drugs as to whether products other than the major brand were available. A sample of physicians identified correctly a mean of 14.1 drugs. Pharmacists who were better informed as to which drugs were available generically were more likely to stock alternative products and more likely to charge lower prices on generic prescriptions than on brand name prescriptions.", "contents": "Savings from generic prescriptions. A study of 33 pharmacies in Rochester, New York. Brand name and gereric prescriptions for 12 drugs were surveyed at 33 pharmacies in the Rochester, New York, area to determine how frequently generic prescriptions were filled with a product other than the major brand, and at a savings to the consumer. Generic prescriptions for ampicillin, erythromycin, propoxyphene, and dioctyl sodium sulfosuccinate were often filled at prices lower than comparable brand name prescriptions. Occasional, but often substantial, savings were obtained for papaverine, pentaerythritol tetranitrate, and conjugated estrogens. No savings were obtained for penicillin V, chlorpheniramine, diphenylhydantoin, sulfisoxazole, or methenamine mandelate. The pharmacists included in the survey identified correctly a mean of 18.5 out of 22 drugs as to whether products other than the major brand were available. A sample of physicians identified correctly a mean of 14.1 drugs. Pharmacists who were better informed as to which drugs were available generically were more likely to stock alternative products and more likely to charge lower prices on generic prescriptions than on brand name prescriptions."} {"id": "PMID:166586", "title": "Ineffectiveness of subcutaneous cytosine arabinoside in localized herpes zoster.", "content": "Cytosine arabinoside (cytarabine) was evaluated in a randomized double-blind controlled study for the treatment of localized herpes zoster. Cytarabine was administered subcutaneously in a dose of 50 mg/m-2 body surface area once daily for 4 days, always within 14 days of onset of the first symptom and usually within 7 days. Thirty patients given cytarabine and 30 patients given placebo were well matched with respect to age, sex, and length and severity of presenting rash and pain as well as underlying disease. There was no difference in the rate of disappearance of pain or rash in either treatment group. More patients given cytarabine than patients given placebo had minimal pain and significantly more cytarabine-treated patients had persistence of neurological symptoms at 6 months' follow-up. Acute side effects, though mild, were significantly increased in the cytarabine-treated patients especially with respect to nausea and vomiting and decrease in platelet count. Cytarabine administered in this dose subcutaneously had no beneficial effect and was associated with mild side effects and persistence of neurological symptoms.", "contents": "Ineffectiveness of subcutaneous cytosine arabinoside in localized herpes zoster. Cytosine arabinoside (cytarabine) was evaluated in a randomized double-blind controlled study for the treatment of localized herpes zoster. Cytarabine was administered subcutaneously in a dose of 50 mg/m-2 body surface area once daily for 4 days, always within 14 days of onset of the first symptom and usually within 7 days. Thirty patients given cytarabine and 30 patients given placebo were well matched with respect to age, sex, and length and severity of presenting rash and pain as well as underlying disease. There was no difference in the rate of disappearance of pain or rash in either treatment group. More patients given cytarabine than patients given placebo had minimal pain and significantly more cytarabine-treated patients had persistence of neurological symptoms at 6 months' follow-up. Acute side effects, though mild, were significantly increased in the cytarabine-treated patients especially with respect to nausea and vomiting and decrease in platelet count. Cytarabine administered in this dose subcutaneously had no beneficial effect and was associated with mild side effects and persistence of neurological symptoms."} {"id": "PMID:166600", "title": "Recent advances in calcium and phosphorus metabolism.", "content": "This review considers the most recent developments concerning the metabolism and homeostasis of calcium and phosphorus. The kinetics of the distribution of calcium, theories of calculus formation, hypercalcemia and hypocalcemia are discussed, as well as the role of parathyroid hormone, thyrocalcitonin and 1,25 dihydroxy Vitamin D(3) in maintaining calcium levels and skeletal integrity. In addition, the role of calcium in enzyme activation and inhibition, muscle and nerve function, and intracellular metabolism are considered.", "contents": "Recent advances in calcium and phosphorus metabolism. This review considers the most recent developments concerning the metabolism and homeostasis of calcium and phosphorus. The kinetics of the distribution of calcium, theories of calculus formation, hypercalcemia and hypocalcemia are discussed, as well as the role of parathyroid hormone, thyrocalcitonin and 1,25 dihydroxy Vitamin D(3) in maintaining calcium levels and skeletal integrity. In addition, the role of calcium in enzyme activation and inhibition, muscle and nerve function, and intracellular metabolism are considered."} {"id": "PMID:166601", "title": "Metabolic and biochemical considerations of bone.", "content": "Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous.", "contents": "Metabolic and biochemical considerations of bone. Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous."} {"id": "PMID:166609", "title": "[Determination of penicillinase and acylase by chromatography on a thin layer of sorbent in the case of their joint formation by different strains].", "content": "The products of penicillinase and acylase hydrolysis of benzylpenicillin were studied with a method of sorbent thin-layer chromatography. The method provided qualitative determination and differentiation of penicillinase and acylase activity in cultures of E. coli capable of simultaneous production of both enzymes. It was shown that when the cultures of E. coli were grown under conditions optimal for acylase production, the amounts of penicillinase were insignificant.", "contents": "[Determination of penicillinase and acylase by chromatography on a thin layer of sorbent in the case of their joint formation by different strains]. The products of penicillinase and acylase hydrolysis of benzylpenicillin were studied with a method of sorbent thin-layer chromatography. The method provided qualitative determination and differentiation of penicillinase and acylase activity in cultures of E. coli capable of simultaneous production of both enzymes. It was shown that when the cultures of E. coli were grown under conditions optimal for acylase production, the amounts of penicillinase were insignificant."} {"id": "PMID:166610", "title": "Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels.", "content": "The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients after a single subcutaneous injection of 50 mg/M(2) exceeded this inhibitory level for a period of 75 min. Thus, the subcutaneous route is a potentially useful method of administration of cytarabine for antiviral drug trials.", "contents": "Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels. The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients after a single subcutaneous injection of 50 mg/M(2) exceeded this inhibitory level for a period of 75 min. Thus, the subcutaneous route is a potentially useful method of administration of cytarabine for antiviral drug trials."} {"id": "PMID:166611", "title": "Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice.", "content": "Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-beta-d-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-beta-d-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus.", "contents": "Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice. Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-beta-d-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-beta-d-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus."} {"id": "PMID:166612", "title": "Desferrioxamine B, an inhibitor of Escherichia coli motility, reversing the stimulating effect of cyclic adenosine 3',5'-monophosphate.", "content": "A substance inhibiting Escherichia coli motility was isolated by \"motilometry\" assay from the culture broth of Streptomyces sp. strain NR9GG8 and was found to be identical with desferrioxamine B. Its inhibitory effect was reversed by cyclic adenosine 3',5'-monophosphate (cAMP), while the motility stimulation by cAMP was diminished by this inhibitor. Its effects on various enzymes involved in cAMP metabolism of function of cAMP were examined.", "contents": "Desferrioxamine B, an inhibitor of Escherichia coli motility, reversing the stimulating effect of cyclic adenosine 3',5'-monophosphate. A substance inhibiting Escherichia coli motility was isolated by \"motilometry\" assay from the culture broth of Streptomyces sp. strain NR9GG8 and was found to be identical with desferrioxamine B. Its inhibitory effect was reversed by cyclic adenosine 3',5'-monophosphate (cAMP), while the motility stimulation by cAMP was diminished by this inhibitor. Its effects on various enzymes involved in cAMP metabolism of function of cAMP were examined."} {"id": "PMID:166625", "title": "Lead. Possible toxicity in urban vs rural rats.", "content": "The degree of lead poisoning in wild rats from two environments has been studied. Wild rats captured in an urban area had markedly elevated tissue lead compared with values in rural rats. This elevation may have been caused by differences in factors affecting absorption of ingested lead or an elevated respiratory exposure to airborne lead, or both, and lead in precipitated dust. Changes in several biologic indexes (depression of delta-amino levulinic acid dehydratase in kidney and red blood cells, presence of renal intranuclear inclusion bodies, and increased kidney weight) confirmed lead-poisoning in urban rats.", "contents": "Lead. Possible toxicity in urban vs rural rats. The degree of lead poisoning in wild rats from two environments has been studied. Wild rats captured in an urban area had markedly elevated tissue lead compared with values in rural rats. This elevation may have been caused by differences in factors affecting absorption of ingested lead or an elevated respiratory exposure to airborne lead, or both, and lead in precipitated dust. Changes in several biologic indexes (depression of delta-amino levulinic acid dehydratase in kidney and red blood cells, presence of renal intranuclear inclusion bodies, and increased kidney weight) confirmed lead-poisoning in urban rats."} {"id": "PMID:166626", "title": "Radioisotopic detection of osseius metastases. Evaluation of 99mTc polyphosphate and 99mTc pyrophosphate.", "content": "A total of 146 patients were investigated for the presence of osseous metastases with 99mTc polyphosphate or 99mTc pyrophosphate bone scans. Results of bone imaging were retrospectively compared to roentgenographic results surveying similar anatomic areas in 128 patients. This comparison revealed that roentgenographic interpretations were in error in 19% of the cases. Thirty-three patients had bone scans and roentgenograms that were in agreement and considered abnormal, but in more than one third of these cases the patients had multiple abnormalities that were shown by the bone scan but were not recognized roentgenographically. In consideration of the low toxicity, ready availability, economy, shortened procedure time, and low radiation dose associated with the use of these new bone-seeking agents, it is concluded that they are superior to roentgenograms and previously utilized radionuclides for early detection of osseous metastases.", "contents": "Radioisotopic detection of osseius metastases. Evaluation of 99mTc polyphosphate and 99mTc pyrophosphate. A total of 146 patients were investigated for the presence of osseous metastases with 99mTc polyphosphate or 99mTc pyrophosphate bone scans. Results of bone imaging were retrospectively compared to roentgenographic results surveying similar anatomic areas in 128 patients. This comparison revealed that roentgenographic interpretations were in error in 19% of the cases. Thirty-three patients had bone scans and roentgenograms that were in agreement and considered abnormal, but in more than one third of these cases the patients had multiple abnormalities that were shown by the bone scan but were not recognized roentgenographically. In consideration of the low toxicity, ready availability, economy, shortened procedure time, and low radiation dose associated with the use of these new bone-seeking agents, it is concluded that they are superior to roentgenograms and previously utilized radionuclides for early detection of osseous metastases."} {"id": "PMID:166627", "title": "The effect of acetylethyleneimine upon a strain of inactivated foot-and-mouth disease virus stored at 4 degrees C.", "content": "The presence of either thiosulphate-neutralized or free AEI was shown to degrade inactivated foot-and-mouth disease virus Type O (Hong Kong) antigen during storage at 4 degrees C. Deterioration was evident after 20 weeks of storage and little antigen remained at 36 weeks. Optimum stability was obtained by removing the residual inactivant immediately after inactivation.", "contents": "The effect of acetylethyleneimine upon a strain of inactivated foot-and-mouth disease virus stored at 4 degrees C. The presence of either thiosulphate-neutralized or free AEI was shown to degrade inactivated foot-and-mouth disease virus Type O (Hong Kong) antigen during storage at 4 degrees C. Deterioration was evident after 20 weeks of storage and little antigen remained at 36 weeks. Optimum stability was obtained by removing the residual inactivant immediately after inactivation."} {"id": "PMID:166628", "title": "Poliovirus-induced infectious double-stranded RNA: Effect of RNA-degrading enzymes.", "content": "The infectivity of replicative form RNA (RF-RNA) isolated from poliovirus-infected HeLa cells is completely resistant to the action of T-1 RNase but decreases after exposure to RNase A in the presence of 0.3 M NaCl. Under these conditions neither enzyme produces single-stranded nicks in RF-RNA. Three endonuclease-free exonuleases (RNase II, polynucleotide phosphorylase and spleen phosphodiesterase) rapidly destroy the infectivity of single-stranded RNA, but do not alter the infectivity of RF-RNA. It is concluded that RF-RNA does not contain single-stranded ends essential for infectivity. Indirect evidence suggests that all or most of the poly A region at the 3' end of the plus strand of infectious RF-RNA is base-paired to a poly U region at the 5 end of the minus strand.", "contents": "Poliovirus-induced infectious double-stranded RNA: Effect of RNA-degrading enzymes. The infectivity of replicative form RNA (RF-RNA) isolated from poliovirus-infected HeLa cells is completely resistant to the action of T-1 RNase but decreases after exposure to RNase A in the presence of 0.3 M NaCl. Under these conditions neither enzyme produces single-stranded nicks in RF-RNA. Three endonuclease-free exonuleases (RNase II, polynucleotide phosphorylase and spleen phosphodiesterase) rapidly destroy the infectivity of single-stranded RNA, but do not alter the infectivity of RF-RNA. It is concluded that RF-RNA does not contain single-stranded ends essential for infectivity. Indirect evidence suggests that all or most of the poly A region at the 3' end of the plus strand of infectious RF-RNA is base-paired to a poly U region at the 5 end of the minus strand."} {"id": "PMID:166630", "title": "Seizure activity and anticonvulsant drug concentration.", "content": "Current methods permit frequent, accurate serum anticonvulsant drug concentration measurements and continuous, 24-hour electroencephalographic recording with minimal environmental restriction. These techniques were used to perform longitudinal, 24-hour recordings of electroencephalographic paroxysmal activity and sleep-wake state concurrently with frequent measurements of serum anticonvulsant drug concentrations in two patients with poorly controlled convulsions. Drug administration was designed with the intent of producing high serum concentrations at times of maximum electroencephalographic paroxysmal activity. The suppression of clinical seizures coincided with decreased numbers of paroxysmal bursts in the electroencephalogram and increased serum anticonvulsant drug concentration.", "contents": "Seizure activity and anticonvulsant drug concentration. Current methods permit frequent, accurate serum anticonvulsant drug concentration measurements and continuous, 24-hour electroencephalographic recording with minimal environmental restriction. These techniques were used to perform longitudinal, 24-hour recordings of electroencephalographic paroxysmal activity and sleep-wake state concurrently with frequent measurements of serum anticonvulsant drug concentrations in two patients with poorly controlled convulsions. Drug administration was designed with the intent of producing high serum concentrations at times of maximum electroencephalographic paroxysmal activity. The suppression of clinical seizures coincided with decreased numbers of paroxysmal bursts in the electroencephalogram and increased serum anticonvulsant drug concentration."} {"id": "PMID:166631", "title": "Nonviral intranuclear filamentous inclusions.", "content": "Intranuclear filamentous structures have been found in cells of both central and peripheral nervous tissues in eight patients with a variety of neurologic diseases. The structures were curly, fibrillary strands, resembling paramyxoviral filaments morphologically, but larger in diameter (25 to 40nm). Their appearance was granular with indistinct, hazy outlines, and on cross section they were solid rather than tubular. These structures are probably not viral but chromatin fibers. The illustration of sequential development of the fibrillary structures from usual chromatin clumps supports this view. Thus, the finding of intranuclear fibrillary material in the cells of a number of patients with neurologic diseases must be interpreted with caution.", "contents": "Nonviral intranuclear filamentous inclusions. Intranuclear filamentous structures have been found in cells of both central and peripheral nervous tissues in eight patients with a variety of neurologic diseases. The structures were curly, fibrillary strands, resembling paramyxoviral filaments morphologically, but larger in diameter (25 to 40nm). Their appearance was granular with indistinct, hazy outlines, and on cross section they were solid rather than tubular. These structures are probably not viral but chromatin fibers. The illustration of sequential development of the fibrillary structures from usual chromatin clumps supports this view. Thus, the finding of intranuclear fibrillary material in the cells of a number of patients with neurologic diseases must be interpreted with caution."} {"id": "PMID:166632", "title": "Moebius syndrome in Kallmann syndrome.", "content": "A girl born with congenital paresis of cranial nerves III, IV, and VII (Moeblus syndrome) subsequently developed a progressive peripheral neuropathy. There was suggestive evidence of a familial neuropathy with autosomal dominant inheritance in three family members. The patient also had hypogonadotrophic hypogonadism and anosmia (Kallmann syndrome).", "contents": "Moebius syndrome in Kallmann syndrome. A girl born with congenital paresis of cranial nerves III, IV, and VII (Moeblus syndrome) subsequently developed a progressive peripheral neuropathy. There was suggestive evidence of a familial neuropathy with autosomal dominant inheritance in three family members. The patient also had hypogonadotrophic hypogonadism and anosmia (Kallmann syndrome)."} {"id": "PMID:166633", "title": "Carcinoma metastatic to the eye and orbit II. A clinicopathological study of 26 patients with carcinoma metastatic to the anterior segment of the eye.", "content": "In 26 of 227 patients with carcinoma metastatic to the eye or orbit, metastasis to the anterior uveal tract was the predominating feature. There was a definite propensity for the tumor to involve the horizontal meridian of the iris or ciliary body, rather than the upper or lower portions. The site of the primary tumor in the 26 patients was as follows: lung 14; breast, 9; kidney, 2; and rectum, 1. Ocular symptoms and signs produced by the metastatic tumors at onset or during the course of the disease included decreased vision (80%), a visible mass (72%), redness of the eye (56%), pain (56%), glaucoma (56%), iridocylitis (44%), and hyphema (24%). The median survival of the 26 patients with metastasis to the anterior segment of the eye was only 5.4 months from the time of ocular surgery. This is poorer than the median survival (7.2 months) of the patients with metastasis confined to the posterior segment, and much worse than the median survival (15.6 months) of the 28 patients with orbital involvement.", "contents": "Carcinoma metastatic to the eye and orbit II. A clinicopathological study of 26 patients with carcinoma metastatic to the anterior segment of the eye. In 26 of 227 patients with carcinoma metastatic to the eye or orbit, metastasis to the anterior uveal tract was the predominating feature. There was a definite propensity for the tumor to involve the horizontal meridian of the iris or ciliary body, rather than the upper or lower portions. The site of the primary tumor in the 26 patients was as follows: lung 14; breast, 9; kidney, 2; and rectum, 1. Ocular symptoms and signs produced by the metastatic tumors at onset or during the course of the disease included decreased vision (80%), a visible mass (72%), redness of the eye (56%), pain (56%), glaucoma (56%), iridocylitis (44%), and hyphema (24%). The median survival of the 26 patients with metastasis to the anterior segment of the eye was only 5.4 months from the time of ocular surgery. This is poorer than the median survival (7.2 months) of the patients with metastasis confined to the posterior segment, and much worse than the median survival (15.6 months) of the 28 patients with orbital involvement."} {"id": "PMID:166634", "title": "Immunity to chlamydial infections of the eye. IV. Immunity in owl monkeys to reinfection with trachoma.", "content": "In a study of trachoma in owl monkeys, it was found that owl monkeys are equally susceptible to low and high doses of trachoma and that resistance to reinfection persisted for six months in the majority of animals. Previous infections with a single trachoma type did not elicit greater resistance than previous infections with two types. Both serum antibodies and eye secretion titers correlated well with resistance to reinfection, but it is not as yet clear if either or both play a substantial role in immunity to trachoma.", "contents": "Immunity to chlamydial infections of the eye. IV. Immunity in owl monkeys to reinfection with trachoma. In a study of trachoma in owl monkeys, it was found that owl monkeys are equally susceptible to low and high doses of trachoma and that resistance to reinfection persisted for six months in the majority of animals. Previous infections with a single trachoma type did not elicit greater resistance than previous infections with two types. Both serum antibodies and eye secretion titers correlated well with resistance to reinfection, but it is not as yet clear if either or both play a substantial role in immunity to trachoma."} {"id": "PMID:166648", "title": "Use of refractometry to determine nitrogen accumulation in close d circuits.", "content": "We have described a technique by which a portable interference refractometer may be used to determine the accumulation of nitrogen in a totally closed anaesthetic circuit. The inspired mixture contained halothane, oxygen, nitrous oxide and nitrogen. The concentrations of the first two were controlled with u.v. paramagnetic analysers respectively. It was then possible to determine the percentage of nitrous oxide replaced by nitrogen by measuring the refractive power of the mixture.", "contents": "Use of refractometry to determine nitrogen accumulation in close d circuits. We have described a technique by which a portable interference refractometer may be used to determine the accumulation of nitrogen in a totally closed anaesthetic circuit. The inspired mixture contained halothane, oxygen, nitrous oxide and nitrogen. The concentrations of the first two were controlled with u.v. paramagnetic analysers respectively. It was then possible to determine the percentage of nitrous oxide replaced by nitrogen by measuring the refractive power of the mixture."} {"id": "PMID:166649", "title": "Totally closed circuit nitrous oxide/oxygen anaesthesia.", "content": "Totally closed circuit anaesthesia has been used with nitrous oxide/oxygen gas mixtures, supplemented by halothane for spontaneous breathing, or by opiates for artificial ventilation. Oxygen expenditure averaged 227 ml/min, while nitrous oxide expenditure declined exponentially from an initial value of 462 ml/min to 110 ml/min after 2 hr. These flow rated included gas sampled for analysis. Inspired oxygen concentration was maintained at 30 per cent by monitoring with a paramagnetic analyser. Halothane expenditure average 3.5 ml (liquid) per hr. Halothane concentrations in the operating theatre atmosphere did not increase above 0.03 p.p.m.", "contents": "Totally closed circuit nitrous oxide/oxygen anaesthesia. Totally closed circuit anaesthesia has been used with nitrous oxide/oxygen gas mixtures, supplemented by halothane for spontaneous breathing, or by opiates for artificial ventilation. Oxygen expenditure averaged 227 ml/min, while nitrous oxide expenditure declined exponentially from an initial value of 462 ml/min to 110 ml/min after 2 hr. These flow rated included gas sampled for analysis. Inspired oxygen concentration was maintained at 30 per cent by monitoring with a paramagnetic analyser. Halothane expenditure average 3.5 ml (liquid) per hr. Halothane concentrations in the operating theatre atmosphere did not increase above 0.03 p.p.m."} {"id": "PMID:166646", "title": "DNA polymerase activity of cultured rheumatoid synovial cells.", "content": "Cultured synovial cells from 8 patients with rheumatoid arthritis (RA) and 7 subjects without joint disease were assayed and comapred for RNA-directed and DNA-directed DNA polymerase activity. No activity was found in either RA or control specimens using a synthetic RNA template that specificically detects oncornavirus RNA-directed DNA polymerase. The DNA-directed DNA polymerase activity of RA specimens was increased (P less than 0.10) in the high-speed pellet fraction of cell lysates. The possible relationship of these finding to virus infection in RA is disscussed.", "contents": "DNA polymerase activity of cultured rheumatoid synovial cells. Cultured synovial cells from 8 patients with rheumatoid arthritis (RA) and 7 subjects without joint disease were assayed and comapred for RNA-directed and DNA-directed DNA polymerase activity. No activity was found in either RA or control specimens using a synthetic RNA template that specificically detects oncornavirus RNA-directed DNA polymerase. The DNA-directed DNA polymerase activity of RA specimens was increased (P less than 0.10) in the high-speed pellet fraction of cell lysates. The possible relationship of these finding to virus infection in RA is disscussed."} {"id": "PMID:166647", "title": "[Cystic degeneration of the adrenal cortex associated with hyaline membrane].", "content": "Forty-one autopsies in newborns with hyaline membrane were studied. In fourteen cases (34.1%) cystic degeneration of the outermost portion of the adrenal cortex was found. Our results differ from other studies as the lesions were observed in newborns at various gestational ages, with a higher incidence in the group of pre-term babies, small for their gestational age. The constant association of hyaline membrane and adrenal cortex cystic degeneration seem to suggest that both processes may share a common etiopathogenic mechanism, namely hypoxia followed by increased ACTH secretion.", "contents": "[Cystic degeneration of the adrenal cortex associated with hyaline membrane]. Forty-one autopsies in newborns with hyaline membrane were studied. In fourteen cases (34.1%) cystic degeneration of the outermost portion of the adrenal cortex was found. Our results differ from other studies as the lesions were observed in newborns at various gestational ages, with a higher incidence in the group of pre-term babies, small for their gestational age. The constant association of hyaline membrane and adrenal cortex cystic degeneration seem to suggest that both processes may share a common etiopathogenic mechanism, namely hypoxia followed by increased ACTH secretion."} {"id": "PMID:166651", "title": "Massive subchorial thrombohaematoma (Breus' mole).", "content": "Ten placentae with massive subchorionic thrombohaematomas are reported. This lesion, which is composed of maternal clotted blood, separates the chorionic plate of the placenta from the villous chorion and is traversed by the main cotyledonary branches of the fetal circulation. In some instances it dissects into the layers of the chorionic plate. In anatomical terms it is identical to the lesion which has been described in early pregnancy under the title of Breus' mole. Previous reports suggested that the lesion was confined to early pregnancies and was a consequence of fetal death. In our series all ten placentae were from pregnancies of at least 25 weeks' maturity and six were more than 30 weeks. Seven infants were liveborn and three survived the neonatal period. Differential diagnosis is discussed along with aetiology, which is still obscure although earlier theories implicating fetal death may be discounted.", "contents": "Massive subchorial thrombohaematoma (Breus' mole). Ten placentae with massive subchorionic thrombohaematomas are reported. This lesion, which is composed of maternal clotted blood, separates the chorionic plate of the placenta from the villous chorion and is traversed by the main cotyledonary branches of the fetal circulation. In some instances it dissects into the layers of the chorionic plate. In anatomical terms it is identical to the lesion which has been described in early pregnancy under the title of Breus' mole. Previous reports suggested that the lesion was confined to early pregnancies and was a consequence of fetal death. In our series all ten placentae were from pregnancies of at least 25 weeks' maturity and six were more than 30 weeks. Seven infants were liveborn and three survived the neonatal period. Differential diagnosis is discussed along with aetiology, which is still obscure although earlier theories implicating fetal death may be discounted."} {"id": "PMID:166652", "title": "Lipoprotein lipase. Mechanism of formation of triglyceride-rich remnant particles from very low density lipoproteins and chylomicrons.", "content": "The catalytic rate of membrane-supported lipoprotein lipase has been determined for chylomicron and very low density lipoprotein substrates during the formation of triglyceride-depleted (\"remnant\") particles. Both lipoprotein species and their generated remnant products were competitive substrates for lipase activity. Remnant formation from each species was associated with decreasing kc but an unchanged apparent Km. This finding was confirmed from the rate of plot of total triglyceride catabolism by lipase at low substrate concentrations. When compared with the major very low density lipoprotein fraction (Sf 100-400), a fraction isolated from plasma with a lower flotation rate (Sf 40-100) had a lipid composition and decreased kc compatible with this representing a physiological remnant particle.", "contents": "Lipoprotein lipase. Mechanism of formation of triglyceride-rich remnant particles from very low density lipoproteins and chylomicrons. The catalytic rate of membrane-supported lipoprotein lipase has been determined for chylomicron and very low density lipoprotein substrates during the formation of triglyceride-depleted (\"remnant\") particles. Both lipoprotein species and their generated remnant products were competitive substrates for lipase activity. Remnant formation from each species was associated with decreasing kc but an unchanged apparent Km. This finding was confirmed from the rate of plot of total triglyceride catabolism by lipase at low substrate concentrations. When compared with the major very low density lipoprotein fraction (Sf 100-400), a fraction isolated from plasma with a lower flotation rate (Sf 40-100) had a lipid composition and decreased kc compatible with this representing a physiological remnant particle."} {"id": "PMID:166653", "title": "Ultraviolet photosensitivity of the estrogen binding protein from rat uterus. Wavelength and ligand dependence. Photocovalent attachment of estrogens to proteins.", "content": "Ultraviolet irradiation of the estrogen binding protein in rat uterine cytosol results in a progressive photoinactivation which is rapid at 254 nm and slower at greater than 315 nm. Both unfilled and estradiol-filled sites are inactivated at approimately the same rates at 254 nm (t 1/2 equals 8 min and 11 min, respectively), but at 315 nm, empty sites are consumed much more rapidly (t 1/2 equals 3.4 hr) than filled ones (t 1/2 equals 24 hr). The protective effect of the estrogen ligand at this wavelength appears to depend on its binding to the estrogen-specific binding site, as inactivation rate studies at different concentrations of estrone, estradiol, and estriol show a good correlation between the extent of protection and the fractional saturation of the high affinity estrogen binding sites. Scatchard analysis indicates that inactivation is the result of a loss of binding sites and not a decrease in their affinity, and sedimentation analysis shows that increased heterogeneity and aggregation of the estrogen binding species accompanies the photoinactivation process. Photoinactivation appears to be the result of direct irradiative damage of the animo acid residues, as the inactivation rate is the same under air and nitrogen atmospheres, and is unaffected by nucleophiles, reductants, and radical scavengers. When photoinactivation is measureed by irradiation of cytosol containing [3-H]estradiol, a concurrent photocovalent attachment process is noted; the steroid becomes linked to protein in a solvent-extractable manner (boiling ethanol inextractable). This attachment, however, does not appear to be related to the steroid binding at the estrogen binding site. Its rate is affected by reductants and scavengers. A similar photocovalent attachment reaction occurs when bovine serum albumin or ovalbumin is irradiated in the presence of [3-H]estradiol or [3-H]diethylstilbestrol. The detailed reactions involved in this photocovalent attachment process have not been defined at present.", "contents": "Ultraviolet photosensitivity of the estrogen binding protein from rat uterus. Wavelength and ligand dependence. Photocovalent attachment of estrogens to proteins. Ultraviolet irradiation of the estrogen binding protein in rat uterine cytosol results in a progressive photoinactivation which is rapid at 254 nm and slower at greater than 315 nm. Both unfilled and estradiol-filled sites are inactivated at approimately the same rates at 254 nm (t 1/2 equals 8 min and 11 min, respectively), but at 315 nm, empty sites are consumed much more rapidly (t 1/2 equals 3.4 hr) than filled ones (t 1/2 equals 24 hr). The protective effect of the estrogen ligand at this wavelength appears to depend on its binding to the estrogen-specific binding site, as inactivation rate studies at different concentrations of estrone, estradiol, and estriol show a good correlation between the extent of protection and the fractional saturation of the high affinity estrogen binding sites. Scatchard analysis indicates that inactivation is the result of a loss of binding sites and not a decrease in their affinity, and sedimentation analysis shows that increased heterogeneity and aggregation of the estrogen binding species accompanies the photoinactivation process. Photoinactivation appears to be the result of direct irradiative damage of the animo acid residues, as the inactivation rate is the same under air and nitrogen atmospheres, and is unaffected by nucleophiles, reductants, and radical scavengers. When photoinactivation is measureed by irradiation of cytosol containing [3-H]estradiol, a concurrent photocovalent attachment process is noted; the steroid becomes linked to protein in a solvent-extractable manner (boiling ethanol inextractable). This attachment, however, does not appear to be related to the steroid binding at the estrogen binding site. Its rate is affected by reductants and scavengers. A similar photocovalent attachment reaction occurs when bovine serum albumin or ovalbumin is irradiated in the presence of [3-H]estradiol or [3-H]diethylstilbestrol. The detailed reactions involved in this photocovalent attachment process have not been defined at present."} {"id": "PMID:166654", "title": "Effects of cyclic adenosine monophosphate, dexamethasone and insulin on phosphoenolpyruvate carboxykinase synthesis in Reuber H-35 hepatoma cells.", "content": "Antiserum prepared against rat liver cytosolic phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) is shown to specifically precipitate the enzyme from Reuber H-35 cells. Synthesis of phosphoenolpyruvate carboxykinase, as measured immunochemically, is increased by dibutyryl cAMP and dexamethasone, the nucleotide maximally producing a sixfold and the glucocorticoid a threefold change in rate. Studies with actinomycin D, cordycepin, and cycloheximide suggest dibutyryl cAMP acts at a translational or post-transcriptional site. Insulin prevents the increase in synthesis of phosphoenolpyruvate carboxykinase produced by either dibutyryl cAMP or dexamethasone. This antagonism is concentration dependent and does not require the simultaneous presence of glucose, pointing to a direct effect of the hormone on liver enzyme induction. It is suggested that hepatic phosphoenolpyruvate carboxykinase activity is regulated predominantly by the antagonistic interaction of cAMP (glucagon) and insulin on enzyme synthesis.", "contents": "Effects of cyclic adenosine monophosphate, dexamethasone and insulin on phosphoenolpyruvate carboxykinase synthesis in Reuber H-35 hepatoma cells. Antiserum prepared against rat liver cytosolic phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) is shown to specifically precipitate the enzyme from Reuber H-35 cells. Synthesis of phosphoenolpyruvate carboxykinase, as measured immunochemically, is increased by dibutyryl cAMP and dexamethasone, the nucleotide maximally producing a sixfold and the glucocorticoid a threefold change in rate. Studies with actinomycin D, cordycepin, and cycloheximide suggest dibutyryl cAMP acts at a translational or post-transcriptional site. Insulin prevents the increase in synthesis of phosphoenolpyruvate carboxykinase produced by either dibutyryl cAMP or dexamethasone. This antagonism is concentration dependent and does not require the simultaneous presence of glucose, pointing to a direct effect of the hormone on liver enzyme induction. It is suggested that hepatic phosphoenolpyruvate carboxykinase activity is regulated predominantly by the antagonistic interaction of cAMP (glucagon) and insulin on enzyme synthesis."} {"id": "PMID:166655", "title": "Binding of hormones to receptors. An alternative explanation of nonlinear Scatchard plots.", "content": "Binding of 1251-labeled hormones to receptors can usually be inhibited by addition of unlabeled hormone. In analyzing such binding-inhibition data, it is commonly assumed that both labeled and unlabeled hormones are bound with equal affinity. When this assumption is made incorrectly, an artifactually nonlinear Scatchard plot results. Equations to describe these nonlinear Scatchard plots are derived. These results are discussed with regard to previously published observations of nonlinear Scatchard plots for binding of insulin to its receptor.", "contents": "Binding of hormones to receptors. An alternative explanation of nonlinear Scatchard plots. Binding of 1251-labeled hormones to receptors can usually be inhibited by addition of unlabeled hormone. In analyzing such binding-inhibition data, it is commonly assumed that both labeled and unlabeled hormones are bound with equal affinity. When this assumption is made incorrectly, an artifactually nonlinear Scatchard plot results. Equations to describe these nonlinear Scatchard plots are derived. These results are discussed with regard to previously published observations of nonlinear Scatchard plots for binding of insulin to its receptor."} {"id": "PMID:166656", "title": "Mechanism of cytochrome c peroxidase. O-benzoylhydroxylamine as an analog of hydrogen peroxide.", "content": "A number of reagents, some of which are electronic analogs of hydrogen peroxide, will replace it in the reactions of cytochrome c peroxidase. These compounds include N-bromosuccinimide, sodium hypochlorite, and the novel oxidizing agent O-benzoylhydroxylamine. If fragments of the oxidant played a functional role in the structure of the oxidized form of the enzyme, it would be expected that the product formed from O-benzoylhydroxylamine would differ from that formed from hydrogen peroxide. The products formed on reaction of the two oxidizing agents with cytochrome c peroxidase are indistinguishable. This results carries implications for the structure of the so-called ES compound. The extension in the range of specific substrates for cytochrome c peroxidase allows identification of the structure which compounds must possess to be oxidizing substrates for the enzyme. A mechanism for the first step of the reaction is suggested. O-Benzoylhydroxylamine is also a reducing agent, and its reaction with the enzyme is analogous to that of hydrogen peroxide with catalase. The final product of the reaction is the inert nitric oxide complex of ferrous cytochrome c peroxidase.", "contents": "Mechanism of cytochrome c peroxidase. O-benzoylhydroxylamine as an analog of hydrogen peroxide. A number of reagents, some of which are electronic analogs of hydrogen peroxide, will replace it in the reactions of cytochrome c peroxidase. These compounds include N-bromosuccinimide, sodium hypochlorite, and the novel oxidizing agent O-benzoylhydroxylamine. If fragments of the oxidant played a functional role in the structure of the oxidized form of the enzyme, it would be expected that the product formed from O-benzoylhydroxylamine would differ from that formed from hydrogen peroxide. The products formed on reaction of the two oxidizing agents with cytochrome c peroxidase are indistinguishable. This results carries implications for the structure of the so-called ES compound. The extension in the range of specific substrates for cytochrome c peroxidase allows identification of the structure which compounds must possess to be oxidizing substrates for the enzyme. A mechanism for the first step of the reaction is suggested. O-Benzoylhydroxylamine is also a reducing agent, and its reaction with the enzyme is analogous to that of hydrogen peroxide with catalase. The final product of the reaction is the inert nitric oxide complex of ferrous cytochrome c peroxidase."} {"id": "PMID:166657", "title": "Mercurated polynucleotides: new probes for hybridization and selective polymer fractionation.", "content": "Polynucleotides containing covalently bound mercury atoms have been prepared by chemical or enzymatic syntheses and some of their physical and biochemical properties studied. The mercury substituents do not appear to alter significantly normal polynucleotide structure. Mercurated polymers function efficiently as templates for nucleic acid polymerases, they are fully susceptible to degradation by standard nucleases, and their denaturation and reannealing properties resemble those of the corresponding nonmercurated polymers. While the Tm's of DNA duplexes are lowered by extensive mercuration, the Tm's of DNA-RNA hybrids and RNA duplexes are either unaffected or elevated. Mercuration, as would be expected, greatly increases the buoyant density of both DNA and RNA. The introduction of as few as one mercury atom per 200 bases permits the selective and quantitative retention of the mercurated polymer probe (and associated nucleotide sequences) on columns of sulfhydryl-agarose. The use of mercurated nucleotides (as polymerase substrates) and oligonucleotides (as primers) in conjunction with sulfhydryl-agarose chromatography provides a simple and efficient method for the isolation of selected polynucleotide sequences, such as specific in vitro transcription products or terminal fragments of duplex DNA. Products absorbed to the affinity resin are readily recovered for further analysis by eluting with buffers containing mercaptoethanol. Although the mercury-carbon bond is somewhat thermolabile, mercurated polynucleotides are suitable as probes in low temperature hybridization studies.", "contents": "Mercurated polynucleotides: new probes for hybridization and selective polymer fractionation. Polynucleotides containing covalently bound mercury atoms have been prepared by chemical or enzymatic syntheses and some of their physical and biochemical properties studied. The mercury substituents do not appear to alter significantly normal polynucleotide structure. Mercurated polymers function efficiently as templates for nucleic acid polymerases, they are fully susceptible to degradation by standard nucleases, and their denaturation and reannealing properties resemble those of the corresponding nonmercurated polymers. While the Tm's of DNA duplexes are lowered by extensive mercuration, the Tm's of DNA-RNA hybrids and RNA duplexes are either unaffected or elevated. Mercuration, as would be expected, greatly increases the buoyant density of both DNA and RNA. The introduction of as few as one mercury atom per 200 bases permits the selective and quantitative retention of the mercurated polymer probe (and associated nucleotide sequences) on columns of sulfhydryl-agarose. The use of mercurated nucleotides (as polymerase substrates) and oligonucleotides (as primers) in conjunction with sulfhydryl-agarose chromatography provides a simple and efficient method for the isolation of selected polynucleotide sequences, such as specific in vitro transcription products or terminal fragments of duplex DNA. Products absorbed to the affinity resin are readily recovered for further analysis by eluting with buffers containing mercaptoethanol. Although the mercury-carbon bond is somewhat thermolabile, mercurated polynucleotides are suitable as probes in low temperature hybridization studies."} {"id": "PMID:166658", "title": "Enzymes regulating glycogen metabolism in swine subcutaneous adipose tissue. I. Phosphorylase and phosphorylase phosphatase.", "content": "Glycogen phosphorylase from swine adipose tissue was purified nearly 700-fold using ethanol precipitation, DEAE-cellulose adsorption, AMP-agarose affinity chromatography, and agarose gel filtration. The purified enzyme migrated as one major and several minor components during polyacrylamide gel electrophoresis. Activity was associated with the major component and at least one of the minor components. The molecular weight of the disaggregated, reduced, and alkylated enzyme, estimated by polyacrylamide gel electrophoresis performed in the presence of sodium dodecyl sulfate, was 90,000. Stability of the purified enzyme was considerably increased in the presence of AMP. The isoelectric pH of the enzyme in crude homogenates was 6.3. The sedimentation coefficient of the purified enzyme (7.9 S) and that in crude homogenates (7.3 S) was determined by sucrose density gradient sedimentation. Optimal pH for activity was between pH 6.5 and 7.1. Apparent Km values for glycogen and inorganic phosphate were 0.9 mg/ml and 6.6 mM, respectively. The Ka for AMP was 0.21 mM. Enzyme activity was increased by K2SO4, KF, KCl, and MgCl2 and decreased by NaCl, Na2SO4, D-glucose, and ATP. Inhibition by glucose was noncompetitive with the activator AMP; inhibition by ATP was partially competitive with AMP. The purified enzyme was activated by incubation with skeletal muscle phosphorylase kinase. Enzyme in crude homogenates was activated by the addition of MgCl2 and ATP; activation was not blocked by addition of protein kinase inhibitor, suggesting that phosphorylase kinase in homogenates of swine adipose tissue is present largely in an activated form. Deactivation of phosphorylase a by phosphorylase phosphatase was studied using enzyme purified approximately 200-fold from swine adipose tissue by ethanol precipitation, DEAE-cellulose chromatography, and gel filtration. The Km of the adipose tissue phosphatase for skeletal muscle phosphorylase a was 6 muM. The purified swine adipose tissue phosphorylase, labeled with 32-P, was inactivated and dephosphorylated by the adipose tissue phosphatase. Dephosphorylation of both skeletal muscle and adipose tissue substrates was inhibited by AMP and glucose reversed this inhibition. Several lines of evidence suggest that AMP inhibition was due to an action on the substrate rather than on the enzyme. We have previously reported that the system for phosphorylase activation in rat fat cells differs in some important characteristics from that in skeletal muscle. However, both swine fat phosphorylase and phosphorylase phosphatase have major properties very similar to those described for the enzymes from skeletal muscle.", "contents": "Enzymes regulating glycogen metabolism in swine subcutaneous adipose tissue. I. Phosphorylase and phosphorylase phosphatase. Glycogen phosphorylase from swine adipose tissue was purified nearly 700-fold using ethanol precipitation, DEAE-cellulose adsorption, AMP-agarose affinity chromatography, and agarose gel filtration. The purified enzyme migrated as one major and several minor components during polyacrylamide gel electrophoresis. Activity was associated with the major component and at least one of the minor components. The molecular weight of the disaggregated, reduced, and alkylated enzyme, estimated by polyacrylamide gel electrophoresis performed in the presence of sodium dodecyl sulfate, was 90,000. Stability of the purified enzyme was considerably increased in the presence of AMP. The isoelectric pH of the enzyme in crude homogenates was 6.3. The sedimentation coefficient of the purified enzyme (7.9 S) and that in crude homogenates (7.3 S) was determined by sucrose density gradient sedimentation. Optimal pH for activity was between pH 6.5 and 7.1. Apparent Km values for glycogen and inorganic phosphate were 0.9 mg/ml and 6.6 mM, respectively. The Ka for AMP was 0.21 mM. Enzyme activity was increased by K2SO4, KF, KCl, and MgCl2 and decreased by NaCl, Na2SO4, D-glucose, and ATP. Inhibition by glucose was noncompetitive with the activator AMP; inhibition by ATP was partially competitive with AMP. The purified enzyme was activated by incubation with skeletal muscle phosphorylase kinase. Enzyme in crude homogenates was activated by the addition of MgCl2 and ATP; activation was not blocked by addition of protein kinase inhibitor, suggesting that phosphorylase kinase in homogenates of swine adipose tissue is present largely in an activated form. Deactivation of phosphorylase a by phosphorylase phosphatase was studied using enzyme purified approximately 200-fold from swine adipose tissue by ethanol precipitation, DEAE-cellulose chromatography, and gel filtration. The Km of the adipose tissue phosphatase for skeletal muscle phosphorylase a was 6 muM. The purified swine adipose tissue phosphorylase, labeled with 32-P, was inactivated and dephosphorylated by the adipose tissue phosphatase. Dephosphorylation of both skeletal muscle and adipose tissue substrates was inhibited by AMP and glucose reversed this inhibition. Several lines of evidence suggest that AMP inhibition was due to an action on the substrate rather than on the enzyme. We have previously reported that the system for phosphorylase activation in rat fat cells differs in some important characteristics from that in skeletal muscle. However, both swine fat phosphorylase and phosphorylase phosphatase have major properties very similar to those described for the enzymes from skeletal muscle."} {"id": "PMID:166659", "title": "The catalytic mechanism of amino acid:tRNA ligases. Synergism and formation of the ternary enzyme-amino acid-ATP complex.", "content": "Formation of binary and ternary enzyme-ligand complexes was investigated for amino acid:tRNA ligases specific for L-isoleucine, L-leucine, and L-phenylalanine. Each of the enzymes exhibited synergistic binding when a substrate was substituted by a structurally related compound. The strength of coupling between the sites binding the amino acid and ATP was strongly dependent on the structure of ligands. The phenomenon was observed with the L-leucine and L-phenylalanine-specific enzymes only in the presence of magnesium. Spermine was inhibitory for L-phenylalanine:tRNA ligase. From the variation which structure of the strength of the observed synergism a correlation scheme was derived considering the ammonium group, the carboxylate group and the side chain of the amino acid, and the adenosine and triphosphate moieties of ATP. The strength of coupling between the subsites binding various combinations of these moieties was evaluated. We found that binding of the subgroups of the amino acid exerts an intramolecular synergism. The strength intramolecular synergism was similar to the strength of the intermolecular synergism observed for the simultaneous binding of an amino alcohol and ATP (or MgATP-2-). We have derived a molecular mechanism for the formation of the ternary enzyme-amino acid-ATP (or MgATP-2-) complex taking into account the synergistic phenomena. The complex is considered to involve electrostatic repulsion between the amino acid carboxylate and the ATP triphosphate moieties. When one of the negatively charged groups have been eliminated, the enzymatic rearrangement which facilitates the formation of this complex may be seen as a synergistic coupling.", "contents": "The catalytic mechanism of amino acid:tRNA ligases. Synergism and formation of the ternary enzyme-amino acid-ATP complex. Formation of binary and ternary enzyme-ligand complexes was investigated for amino acid:tRNA ligases specific for L-isoleucine, L-leucine, and L-phenylalanine. Each of the enzymes exhibited synergistic binding when a substrate was substituted by a structurally related compound. The strength of coupling between the sites binding the amino acid and ATP was strongly dependent on the structure of ligands. The phenomenon was observed with the L-leucine and L-phenylalanine-specific enzymes only in the presence of magnesium. Spermine was inhibitory for L-phenylalanine:tRNA ligase. From the variation which structure of the strength of the observed synergism a correlation scheme was derived considering the ammonium group, the carboxylate group and the side chain of the amino acid, and the adenosine and triphosphate moieties of ATP. The strength of coupling between the subsites binding various combinations of these moieties was evaluated. We found that binding of the subgroups of the amino acid exerts an intramolecular synergism. The strength intramolecular synergism was similar to the strength of the intermolecular synergism observed for the simultaneous binding of an amino alcohol and ATP (or MgATP-2-). We have derived a molecular mechanism for the formation of the ternary enzyme-amino acid-ATP (or MgATP-2-) complex taking into account the synergistic phenomena. The complex is considered to involve electrostatic repulsion between the amino acid carboxylate and the ATP triphosphate moieties. When one of the negatively charged groups have been eliminated, the enzymatic rearrangement which facilitates the formation of this complex may be seen as a synergistic coupling."} {"id": "PMID:166660", "title": "Phosphorylation of the lysine-rich histones throughout the cell cycle.", "content": "The phosphorylating of the lysine-rich histone at various stages in the cell cycle has been studied. In rapidly dividing cell populations the lysine-rich histone is phosphorylated rapidly after synthesis and more slowly once bound to the chromosome. The half-life of hydrolysis of such interphase phosphorylation in 5 hr except during mitosis when the phosphata hydrolysis increases almost three-fold. During mitosis there is extensive phosphorylation at sites different from those phosphorylated during interphase and a smaller measure of sites common to both mitotic and interphase cells. The sites of mitotic phosphorylation are most critically distinguished from those phosphorylated in interphase by the rapidly hydrolysis of M-phase phosphohistone when the cells divide and enter the G1 phase of the cell cycle.", "contents": "Phosphorylation of the lysine-rich histones throughout the cell cycle. The phosphorylating of the lysine-rich histone at various stages in the cell cycle has been studied. In rapidly dividing cell populations the lysine-rich histone is phosphorylated rapidly after synthesis and more slowly once bound to the chromosome. The half-life of hydrolysis of such interphase phosphorylation in 5 hr except during mitosis when the phosphata hydrolysis increases almost three-fold. During mitosis there is extensive phosphorylation at sites different from those phosphorylated during interphase and a smaller measure of sites common to both mitotic and interphase cells. The sites of mitotic phosphorylation are most critically distinguished from those phosphorylated in interphase by the rapidly hydrolysis of M-phase phosphohistone when the cells divide and enter the G1 phase of the cell cycle."} {"id": "PMID:166661", "title": "A novel pathway for phosphatidylcholine catabolism in rat brain homogenates.", "content": "Rat brain homogenates incubated with exogenous [32-P] phosphatidylcholine liberated: LYSO[32-P] phosphatidylcholine, sn-glycero-3-[32-P] phosphorylcholine, [32-P] phosphorylcholine, sn-gleycero-3-[32-P] phosphate and 32-Pi. Further investigation showed that [32-P] phosphorylcholine was released exclusively from sn-glycero-3-[32-P] phosphorylcholien by a novel diesterase activity. We propose that the enzyme be termed L-3-glycerylphosphinicocholine cholinephosphohydrolase (EC 3.1.4.-). Parallel experiments on rat liver homogenates and a P815Y mouse mastocytoma cell-lysate, revealed no diesterase activity.", "contents": "A novel pathway for phosphatidylcholine catabolism in rat brain homogenates. Rat brain homogenates incubated with exogenous [32-P] phosphatidylcholine liberated: LYSO[32-P] phosphatidylcholine, sn-glycero-3-[32-P] phosphorylcholine, [32-P] phosphorylcholine, sn-gleycero-3-[32-P] phosphate and 32-Pi. Further investigation showed that [32-P] phosphorylcholine was released exclusively from sn-glycero-3-[32-P] phosphorylcholien by a novel diesterase activity. We propose that the enzyme be termed L-3-glycerylphosphinicocholine cholinephosphohydrolase (EC 3.1.4.-). Parallel experiments on rat liver homogenates and a P815Y mouse mastocytoma cell-lysate, revealed no diesterase activity."} {"id": "PMID:166662", "title": "Characterization of a membrane-bound phospholipid desaturase system of candida lipolytica.", "content": "Several characteristics of the microsomal phospholipid desaturase of Candida lipolytica are described. The phospholipid desaturase reaction required molecular oxygen and reduced pyridine nucleotides as essential cofactors and was inhibited by cyanide but not by carbonmonoxide, indicating that it required cytochrome b5. Desaturation of both 1-acyl-2-[14-C]oleoyl-sn-glycero-3-phosphorylcholine and 1,2-di-[14C] oleoyl-sn-glycero-3-phosphorylcholine appeared to follow Michaelis-Menten kinetics, with apparent Km values of 2.5 10-minus 4 M and 9.5 10-minus 4 M, respectively. Desaturation of the di-[14C] oleoylphosphatidylcholine took place at both position-1 and position-2; the distearoyl or dielaidoyl phosphatidylcholines were not desaturated. Rate of desaturation of the 1=acyl-2-[14-C] oleoyl-glycerophosphorylcholine by microsomes from cold-grown cells was equal to or slightly less than that by microsomes from cells grown at the normal growth temperature of 25 degreesC, measured in the temperature range 10-30 degrees C. However, the rate of desaturation of [14-C]-oleoyl-CoA desaturase was greater with the microsomal preparation from cold-grown cells than with that from 25 degreesC grown cells. These data suggest that the observed increase of diunsaturated fatty acids in cold-grown cells may perhaps be explained by the increased activity of the oleoyl-CoA desaturase acting at the low temperature.", "contents": "Characterization of a membrane-bound phospholipid desaturase system of candida lipolytica. Several characteristics of the microsomal phospholipid desaturase of Candida lipolytica are described. The phospholipid desaturase reaction required molecular oxygen and reduced pyridine nucleotides as essential cofactors and was inhibited by cyanide but not by carbonmonoxide, indicating that it required cytochrome b5. Desaturation of both 1-acyl-2-[14-C]oleoyl-sn-glycero-3-phosphorylcholine and 1,2-di-[14C] oleoyl-sn-glycero-3-phosphorylcholine appeared to follow Michaelis-Menten kinetics, with apparent Km values of 2.5 10-minus 4 M and 9.5 10-minus 4 M, respectively. Desaturation of the di-[14C] oleoylphosphatidylcholine took place at both position-1 and position-2; the distearoyl or dielaidoyl phosphatidylcholines were not desaturated. Rate of desaturation of the 1=acyl-2-[14-C] oleoyl-glycerophosphorylcholine by microsomes from cold-grown cells was equal to or slightly less than that by microsomes from cells grown at the normal growth temperature of 25 degreesC, measured in the temperature range 10-30 degrees C. However, the rate of desaturation of [14-C]-oleoyl-CoA desaturase was greater with the microsomal preparation from cold-grown cells than with that from 25 degreesC grown cells. These data suggest that the observed increase of diunsaturated fatty acids in cold-grown cells may perhaps be explained by the increased activity of the oleoyl-CoA desaturase acting at the low temperature."} {"id": "PMID:166663", "title": "Endogenous steroid production in cellular and subcellular fractions of rat testis after prolonged treatment with gonadotropins.", "content": "Steroid production and enzyme activities were examined in preparations of whole testis tissue, isolated interstitial tissue and seminiferous tubules obtained from adult rats with intact pituitaries receiving daily subcutaneous injections of 100 I.U. human chorionic gonadotropin for 5 days and from control animals. After human chorionic gonadotropin administration testosterone concentrations were increased in total homogenates of whole testis tissue, interstitial tissue and seminiferous tubules. The testosterone production from endogenous precursors was enhanced only in total homogenates of whole testis tissue and interstitial tissue obtained from testes of human chorionic gonadotropin-treated rats. The production of testosterone in the corresponding homogenates of isolated seminiferous tubules was very low. The specific activity of 3 beta-hydroxysteroid dehydrogenase was increased in total homogenates of whole testis tissue, isolated interstitial tissue and seminiferous tubules. No effect was observed on the specific activities of marker enzymes such as cytochrome c oxidase, monoamine oxidase, steroid sulfatase and lactate dehydrogenase, whereas the specific activities of carboxyl esterase were decreased in homogenates of whole testis tissue and interstitial tissue. Total activity of monoamine oxidase was increased in homogenates of interstitial tissue of tests from human chorionic gonadotropin treated rats. After the same prolonged human chorionic gonadotropin treatment the concentration of pregnenolone was increased in mitochondrial fractions of whole testis tissue, interstitial tissue and seminiferous tubules, and the amount of protein isolated in the mitochondrial fraction of interstitial tissue increased by 40%. Steroid production (estimated as pregnenolone) from endogenous precusors by mitochondrial fractions of whole testis tissue and interstitial tissue were increased after human chorionic gonadotropin treatment, for whole testis from 580 pmol/mg mitochondrial protein per h to 1420 pmol/mg per h; and for interstitial tissue from 2665 pmol/mg per h to 7050 pmol/mg per h. The production of pregnenolone in mitochondrial fractions obtaine from isolated seminiferous tubules was very low and contributed hardly at all to the total pregnenolone production in mitochondrial fractions of whole testis tissue from normal rats as well as from human chorionic gonadotropin-treated rats.", "contents": "Endogenous steroid production in cellular and subcellular fractions of rat testis after prolonged treatment with gonadotropins. Steroid production and enzyme activities were examined in preparations of whole testis tissue, isolated interstitial tissue and seminiferous tubules obtained from adult rats with intact pituitaries receiving daily subcutaneous injections of 100 I.U. human chorionic gonadotropin for 5 days and from control animals. After human chorionic gonadotropin administration testosterone concentrations were increased in total homogenates of whole testis tissue, interstitial tissue and seminiferous tubules. The testosterone production from endogenous precursors was enhanced only in total homogenates of whole testis tissue and interstitial tissue obtained from testes of human chorionic gonadotropin-treated rats. The production of testosterone in the corresponding homogenates of isolated seminiferous tubules was very low. The specific activity of 3 beta-hydroxysteroid dehydrogenase was increased in total homogenates of whole testis tissue, isolated interstitial tissue and seminiferous tubules. No effect was observed on the specific activities of marker enzymes such as cytochrome c oxidase, monoamine oxidase, steroid sulfatase and lactate dehydrogenase, whereas the specific activities of carboxyl esterase were decreased in homogenates of whole testis tissue and interstitial tissue. Total activity of monoamine oxidase was increased in homogenates of interstitial tissue of tests from human chorionic gonadotropin treated rats. After the same prolonged human chorionic gonadotropin treatment the concentration of pregnenolone was increased in mitochondrial fractions of whole testis tissue, interstitial tissue and seminiferous tubules, and the amount of protein isolated in the mitochondrial fraction of interstitial tissue increased by 40%. Steroid production (estimated as pregnenolone) from endogenous precusors by mitochondrial fractions of whole testis tissue and interstitial tissue were increased after human chorionic gonadotropin treatment, for whole testis from 580 pmol/mg mitochondrial protein per h to 1420 pmol/mg per h; and for interstitial tissue from 2665 pmol/mg per h to 7050 pmol/mg per h. The production of pregnenolone in mitochondrial fractions obtaine from isolated seminiferous tubules was very low and contributed hardly at all to the total pregnenolone production in mitochondrial fractions of whole testis tissue from normal rats as well as from human chorionic gonadotropin-treated rats."} {"id": "PMID:166664", "title": "Structural differences in ferritins from normal and malignant rat tissues.", "content": "Ferritins purified from several normal and malignant rat tissues were examined for amino acid composition, content of tryptic peptides, available sulfhydryl groups and subunit sizes and proportion. Ferritin extracted from adult kidney, neonatal liver and hepatic and renal tumors differed from the ferritin of adult rat liver in migration on electrophoretic gels and in antibody affinity, but did not differ among themselves. Nevertheless, they showed distinctive differences in amino acid composition and tryptic peptide content. All of them and also adult liver ferritin contained two major species of subunits differing in molecular weight. The proportions of subunits, and the available sulfhydryl groups of the intact ferritin molecules, differed among these tissue ferritins. On the basis of amino acid and peptide content, the ferritins of hepatomas and the renal tumor analyzed showec the greatest similarity but not identity. The ferritin of neonatal liver was next most similar. Kidney ferritin differed considerably in composition from tumor and neonatal ferritins, while adult liver ferritin was the most extremely divergent of the series examined. A similar progressive difference was found on examining the proportions of subunits and sulfhydryl groups in these ferritins. However, changes in subunit proportion cannot explain the amino acid and peptide compositional changes.", "contents": "Structural differences in ferritins from normal and malignant rat tissues. Ferritins purified from several normal and malignant rat tissues were examined for amino acid composition, content of tryptic peptides, available sulfhydryl groups and subunit sizes and proportion. Ferritin extracted from adult kidney, neonatal liver and hepatic and renal tumors differed from the ferritin of adult rat liver in migration on electrophoretic gels and in antibody affinity, but did not differ among themselves. Nevertheless, they showed distinctive differences in amino acid composition and tryptic peptide content. All of them and also adult liver ferritin contained two major species of subunits differing in molecular weight. The proportions of subunits, and the available sulfhydryl groups of the intact ferritin molecules, differed among these tissue ferritins. On the basis of amino acid and peptide content, the ferritins of hepatomas and the renal tumor analyzed showec the greatest similarity but not identity. The ferritin of neonatal liver was next most similar. Kidney ferritin differed considerably in composition from tumor and neonatal ferritins, while adult liver ferritin was the most extremely divergent of the series examined. A similar progressive difference was found on examining the proportions of subunits and sulfhydryl groups in these ferritins. However, changes in subunit proportion cannot explain the amino acid and peptide compositional changes."} {"id": "PMID:166665", "title": "Radioimmunoassay of human high density lipoprotein apo-protein A-1.", "content": "A double antibody radioimmunoassay technique was developed for the measurement of apolipoprotein A-I, the major apoprotein of human high density lipoproteins. Apolipoprotein A-I was prepared from human delipidated high density lipoprotein (d equal to 1.085-1.210) by gel filtration and ion-exchange chromatography. Purified apolipoprotein A-I antibodies were obtained by means of apolipoprotein A-I immunoadsorbent. Apolipoprotein A-I was radiolabeled with 125-I by the iodine monochloride technique. 65-80% of 125 I-labeled apolipoprotein A-I could be bound by the different apolipoprotein A-I antibodies, and more than 95% of the 125-I-labeled apolipoprotein A-I was displaced by unlabeled apolipoprotein A-I. The immunoassay was found to be sensitive for the detection of about 10 ng of apolipoprotein A-I in the incubation mixture, and accurate with a variability of only 3-5% (S.E.M.). This technique enables the quantitation of apolipoprotein A-I in whole plasma or high density lipoprotein without the need of delipidation. The quantitation of apolipoprotein A-I in high density lipoprotein was found similar to that obtained by gel filtration technique. The displacement capacity of the different lipoproteins and apoproteins in comparison to unlabeled apolipoprotein A-I was: very low density lipoprotein, 1.8%; low density lipoprotein, 2.6%; high density lipoprotein, 68%; apolipoprotein B, non-detectable; apolipoprotein C, 0.5%; and apolipoprotein A-II, 4%. The distribution of immunoassayable apolipoprotein A-I among the different plasma lipoproteins was as follows: smaller than 1% in very low density lipoprotein and low density lipoprotein; 50% in high density lipoprotein, and 50% in lipoprotein fraction of density greater than 1.21 g/ml. The amount of apolipoprotein A-I in the latter fraction was found to be related to the number of centrifugations.", "contents": "Radioimmunoassay of human high density lipoprotein apo-protein A-1. A double antibody radioimmunoassay technique was developed for the measurement of apolipoprotein A-I, the major apoprotein of human high density lipoproteins. Apolipoprotein A-I was prepared from human delipidated high density lipoprotein (d equal to 1.085-1.210) by gel filtration and ion-exchange chromatography. Purified apolipoprotein A-I antibodies were obtained by means of apolipoprotein A-I immunoadsorbent. Apolipoprotein A-I was radiolabeled with 125-I by the iodine monochloride technique. 65-80% of 125 I-labeled apolipoprotein A-I could be bound by the different apolipoprotein A-I antibodies, and more than 95% of the 125-I-labeled apolipoprotein A-I was displaced by unlabeled apolipoprotein A-I. The immunoassay was found to be sensitive for the detection of about 10 ng of apolipoprotein A-I in the incubation mixture, and accurate with a variability of only 3-5% (S.E.M.). This technique enables the quantitation of apolipoprotein A-I in whole plasma or high density lipoprotein without the need of delipidation. The quantitation of apolipoprotein A-I in high density lipoprotein was found similar to that obtained by gel filtration technique. The displacement capacity of the different lipoproteins and apoproteins in comparison to unlabeled apolipoprotein A-I was: very low density lipoprotein, 1.8%; low density lipoprotein, 2.6%; high density lipoprotein, 68%; apolipoprotein B, non-detectable; apolipoprotein C, 0.5%; and apolipoprotein A-II, 4%. The distribution of immunoassayable apolipoprotein A-I among the different plasma lipoproteins was as follows: smaller than 1% in very low density lipoprotein and low density lipoprotein; 50% in high density lipoprotein, and 50% in lipoprotein fraction of density greater than 1.21 g/ml. The amount of apolipoprotein A-I in the latter fraction was found to be related to the number of centrifugations."} {"id": "PMID:166666", "title": "The phenoloxidases of the ascomycete Podospora anserina. XI. The state of copper of laccases I, II and III.", "content": "1. Laccases I, II and III were (EC 1.14.18.1) prepared from the mycelium of the ascomycete Podospora anserina. The tetrameric laccase I(mol. wt 340 000, 16 copper atoms) and the monomeric laccases II and II (mol. wt 80 000, 4 copper atoms) have been studied by optical absorption-, circular dichroism-(CD)and electron paramagnetic resonance spectroscopy (EPR). 2. The visible and near ultraviolet difference absorption spectrum, which is apparently identical for all three laccases, shows two maxima at 330 and 610 nm and a shoulder at about 725 nm. The molar extinction coefficients of these bands are 4 times larger for the tetrameric laccase I compared to the monomeric laccases II and III which show values similar to other blue copper-containing oxidases. 3. CD spectra between 300 and 730 nm of the tree laccases are similar and contain at least 5-bands in the oxidized enzyme. If the enzyme is reduced, only a band at 307 nm remains. The molar ellipticity values of these bands are 4 times larger for laccase I than the corresponding bands of laccases II and III. It is inferred that the reducible bands are associated with the Type 1 Cu-2+. 4. In all three laccases the EPR-detectable copper accounts for only about 50% of the total copper content. The 9-GHz and 35-GHz spectra, which are identical for all three laccases, consist of two components of equal intensity. One component shows a rather small copper hyperfine coupling and a small deviation from axial symmetry. It is suggested that this copper is associated with the blue chromophore in analogy to Type 1 Cu-2+ in other blue copper proteins. The other component has a broader hyperfine coupling similar to Type 2 Cu-2+ as found in other copper proteins. The assumption that the experimental spectra result from a superposition of the spectra of equal amounts of Type 1 and Type 2 Cu-2+ has been verified by computer simulation. 5. It is suggested that the copper ions which are not detected by EPR are connected to the absorption band at 330 nm and that these ions are also essential for the function of these laccases.", "contents": "The phenoloxidases of the ascomycete Podospora anserina. XI. The state of copper of laccases I, II and III. 1. Laccases I, II and III were (EC 1.14.18.1) prepared from the mycelium of the ascomycete Podospora anserina. The tetrameric laccase I(mol. wt 340 000, 16 copper atoms) and the monomeric laccases II and II (mol. wt 80 000, 4 copper atoms) have been studied by optical absorption-, circular dichroism-(CD)and electron paramagnetic resonance spectroscopy (EPR). 2. The visible and near ultraviolet difference absorption spectrum, which is apparently identical for all three laccases, shows two maxima at 330 and 610 nm and a shoulder at about 725 nm. The molar extinction coefficients of these bands are 4 times larger for the tetrameric laccase I compared to the monomeric laccases II and III which show values similar to other blue copper-containing oxidases. 3. CD spectra between 300 and 730 nm of the tree laccases are similar and contain at least 5-bands in the oxidized enzyme. If the enzyme is reduced, only a band at 307 nm remains. The molar ellipticity values of these bands are 4 times larger for laccase I than the corresponding bands of laccases II and III. It is inferred that the reducible bands are associated with the Type 1 Cu-2+. 4. In all three laccases the EPR-detectable copper accounts for only about 50% of the total copper content. The 9-GHz and 35-GHz spectra, which are identical for all three laccases, consist of two components of equal intensity. One component shows a rather small copper hyperfine coupling and a small deviation from axial symmetry. It is suggested that this copper is associated with the blue chromophore in analogy to Type 1 Cu-2+ in other blue copper proteins. The other component has a broader hyperfine coupling similar to Type 2 Cu-2+ as found in other copper proteins. The assumption that the experimental spectra result from a superposition of the spectra of equal amounts of Type 1 and Type 2 Cu-2+ has been verified by computer simulation. 5. It is suggested that the copper ions which are not detected by EPR are connected to the absorption band at 330 nm and that these ions are also essential for the function of these laccases."} {"id": "PMID:166667", "title": "Inhibition of electron transfer from ferrocytochrome b to ubiquinone, cytochrome c1 and duroquinone by antimycin.", "content": "The effect of antimycin on (i) the respiratory activity of the KCN-insensitive pathway of mitochondria of Neurospora grown on chloramphenicol (chloramphenicol-grown) with durohydroquinone and succinate or NADH as substrate, (ii) the electron transfer from the b-type cytochromes to ubiquinone with durohydroquinone as electron donor as well as (iii) the electron transfer from the b-type cytochromes to duroquinone with succinate as electron donor in chloramphenicol-grown Neurospora and beef heart submitochondrial particles was studied. All experiments were performed in the uncoupled state. 1. The respiratory chain of chloramphenicol-grown Neurospora mitochondria branches at ubiquinone into two pathways. Besides the cytochrome oxidase-dependent pathway, a KCN-insensitive branch equiped with a salicylhydroxamate-sensitive oxidase exists. Durohydroquinone, succinate or NADH are oxidized via both pathways. The durohydroquinone oxidation via the KCN-insensitive pathway is inhibited by antimycin, wheras the succinate or NADH oxidation is not. The titer for ful inhibition is one mol antimycin per mol cytochrome b-563 or cytochrome b-557. 2. The electron transfer from durohydroquinone to ubiquinone, which takes place in the KCN-inhibited state, does not occur in the antimycin-inhibited state. 3. The reduction of duroquinone by succinate in the presence of KCN is inhibited by antimycin. The titer for full inhibition is one mol antimycin per mol cytochrome b-566 or cytochrome b-562 for beef heart (or cytochrome b-563 or cytochrome b-557 for Neurospora). 4. When electron transfer from the b-type cytochromes to cytochrome C1, ubiquinone and duroquinone is inhibited by antimycin, the hemes of cytochrome b-566 and cytochrome b-562 (or cytochrome b-563 and cytochrome b-557) are in the reduced state. 5. The experimental results suggest that the two b-type cytochromes form a binary complex the electron transferring activity of which is inhibited by antimycin, the titer for full inhibition being one mol of antimycin per mol of complex. The electron transfer from the b-type cytochromes to ubiquinone is inhibited in a non-linear fashion.", "contents": "Inhibition of electron transfer from ferrocytochrome b to ubiquinone, cytochrome c1 and duroquinone by antimycin. The effect of antimycin on (i) the respiratory activity of the KCN-insensitive pathway of mitochondria of Neurospora grown on chloramphenicol (chloramphenicol-grown) with durohydroquinone and succinate or NADH as substrate, (ii) the electron transfer from the b-type cytochromes to ubiquinone with durohydroquinone as electron donor as well as (iii) the electron transfer from the b-type cytochromes to duroquinone with succinate as electron donor in chloramphenicol-grown Neurospora and beef heart submitochondrial particles was studied. All experiments were performed in the uncoupled state. 1. The respiratory chain of chloramphenicol-grown Neurospora mitochondria branches at ubiquinone into two pathways. Besides the cytochrome oxidase-dependent pathway, a KCN-insensitive branch equiped with a salicylhydroxamate-sensitive oxidase exists. Durohydroquinone, succinate or NADH are oxidized via both pathways. The durohydroquinone oxidation via the KCN-insensitive pathway is inhibited by antimycin, wheras the succinate or NADH oxidation is not. The titer for ful inhibition is one mol antimycin per mol cytochrome b-563 or cytochrome b-557. 2. The electron transfer from durohydroquinone to ubiquinone, which takes place in the KCN-inhibited state, does not occur in the antimycin-inhibited state. 3. The reduction of duroquinone by succinate in the presence of KCN is inhibited by antimycin. The titer for full inhibition is one mol antimycin per mol cytochrome b-566 or cytochrome b-562 for beef heart (or cytochrome b-563 or cytochrome b-557 for Neurospora). 4. When electron transfer from the b-type cytochromes to cytochrome C1, ubiquinone and duroquinone is inhibited by antimycin, the hemes of cytochrome b-566 and cytochrome b-562 (or cytochrome b-563 and cytochrome b-557) are in the reduced state. 5. The experimental results suggest that the two b-type cytochromes form a binary complex the electron transferring activity of which is inhibited by antimycin, the titer for full inhibition being one mol of antimycin per mol of complex. The electron transfer from the b-type cytochromes to ubiquinone is inhibited in a non-linear fashion."} {"id": "PMID:166668", "title": "EPR studies on the respiratory chain of wild-type Saccharomyces cerevisiae and mutants with a deficiency in succinate dehydrogenase.", "content": "1. Three nuclear mutants of Saccharomyces cerevisiae deficient in succinate dehydrogenase have been isolated. Two of these mutants are allelic. 2. The amount of covalently bound flavin of submitochondrial particles of the two allelic mutants is about 14% and that of the third mutant about 50% of the amount in wild-type particles. The turnover number of succinate dehydrogenase of particles is decreased in all mutants. The turnover number of fumarate reductase is increased in the two allelic mutants, but decreased in the third mutant. 3. EPR spectra, measured at 82 degrees K, show that the amplitude of the g equals 1.93 signal in particles of the two allelic mutants is less than 10% of that in wild-type particles. It is concluded that iron-sulphur centres other than those of succinate dehydrogenase make only a negligible contribution to the line at g equals 1.93 in wild-type particles. 4. EPR measurements below 20 degrees K show that the amplitude of the signal at g equals 2.01 detected in oxidized particles is decreased in particles of the two allelic mutants. 5. A signal with lines at g equals 2.027 and g equals 1.933 is detected at low temperatures in all particle preparations, even in those from a cytoplasmic petite mutant. It is suggested that this signal is derived from a contaminant and not from the inner membrane.", "contents": "EPR studies on the respiratory chain of wild-type Saccharomyces cerevisiae and mutants with a deficiency in succinate dehydrogenase. 1. Three nuclear mutants of Saccharomyces cerevisiae deficient in succinate dehydrogenase have been isolated. Two of these mutants are allelic. 2. The amount of covalently bound flavin of submitochondrial particles of the two allelic mutants is about 14% and that of the third mutant about 50% of the amount in wild-type particles. The turnover number of succinate dehydrogenase of particles is decreased in all mutants. The turnover number of fumarate reductase is increased in the two allelic mutants, but decreased in the third mutant. 3. EPR spectra, measured at 82 degrees K, show that the amplitude of the g equals 1.93 signal in particles of the two allelic mutants is less than 10% of that in wild-type particles. It is concluded that iron-sulphur centres other than those of succinate dehydrogenase make only a negligible contribution to the line at g equals 1.93 in wild-type particles. 4. EPR measurements below 20 degrees K show that the amplitude of the signal at g equals 2.01 detected in oxidized particles is decreased in particles of the two allelic mutants. 5. A signal with lines at g equals 2.027 and g equals 1.933 is detected at low temperatures in all particle preparations, even in those from a cytoplasmic petite mutant. It is suggested that this signal is derived from a contaminant and not from the inner membrane."} {"id": "PMID:166669", "title": "Two mechanisms of near-ultraviolet lethality in Saccharomyces cerevisiae: a respiratory capacity-dependent and an irreversible inactivation.", "content": "Near-ultraviolet irradiation of actively growing yeast cells leads to cell death by two distinct mechanisms. The first type of cell death is evident after low doses of near-ultraviolet light (3 times 10-4 ergs times mm- minus 2) and is due to a reversible inactivation of the respiratory capacity of the cell. In studies with yeast mitochondrial membranes the quinones were identified as the site of inactivation by determining the relative levels of the following oxidase activities after irradiation: exogenous NADH, endogenous NADH (via isocitrate dehydrogenase), succinate, and D-lactate oxidases. A second type of cell death is caused after high doses (1.8 times 10-5 ergs times mm- minus 2) and is irreversible. The mechanism of this inactivation is unknown.", "contents": "Two mechanisms of near-ultraviolet lethality in Saccharomyces cerevisiae: a respiratory capacity-dependent and an irreversible inactivation. Near-ultraviolet irradiation of actively growing yeast cells leads to cell death by two distinct mechanisms. The first type of cell death is evident after low doses of near-ultraviolet light (3 times 10-4 ergs times mm- minus 2) and is due to a reversible inactivation of the respiratory capacity of the cell. In studies with yeast mitochondrial membranes the quinones were identified as the site of inactivation by determining the relative levels of the following oxidase activities after irradiation: exogenous NADH, endogenous NADH (via isocitrate dehydrogenase), succinate, and D-lactate oxidases. A second type of cell death is caused after high doses (1.8 times 10-5 ergs times mm- minus 2) and is irreversible. The mechanism of this inactivation is unknown."} {"id": "PMID:166670", "title": "Thermodynamic and EPR characterization of iron-sulfur centers in the NADH-ubiquinone segment of the mitochondrial respiratory chain in pigeon heart.", "content": "Several iron-sulfur centers in the NADH-ubiquinone segment of the respiratory chain in pigeon heart mitochondria and in submitochondrial particles were analyzed by the combined application of cryogenic EPR (between 30 and 4.2 degrees K) and potentiometric titration. Center N-1 (iron-sulfur centers associated with NADH dehydrogenase are designated with the prefix \"N\") resolves into two single electron titratins with EM7.2 values of minus 380 plus or minus 20 mV and minus 240 plus or minus 20 mV (Centers N-1a and N-1b, respectively). Center N-1a exhibits an EPR spectrum of nearly axial symmetry with g parellel = 2.03, g = 1.94, while that of Center N-1b shows more apparent rhombic symmetry with gz = 2.03, gy = 1.94 and gx = 1.91. Center N-2 also reveals EPR signals of axial symmetry at g parallel = 2.05 and g = 1.93 and its principal signal overlaps with those of Centers N-1a and N-1b. Center N-2 can be easily resolved from N-1a and N-1b because of its high EM7.2 value (minus 20 plus or minus 20 mV). Resolution of Centers N-3 and N-4 was achieved potentiometrically in submitochondrial particles. The component with EM7.2 = minus 240 plus or minus 20 mV is defined as Center N-3 (gz = 2.10, (gz = 2.10, (gy = 1.93?), GX = 1.87); the minus 405 plus or minus 20 mV component as Center N-4 (gz = 2.11, (gy = 1.93?), gx = 1.88). At temperatures close to 4.2 degrees K, EPR signals at g = 2.11, 2.06, 2.03, 1.93, 1.90 and 1.88 titrate with EM7.2 = minus 260 plus or minus 20 mV. The multiplicity of peaks suggests the presence of at least two different iron-sulfur centers having similar EM7.2 values (minus 260 plus or minus 20 mV); HENCE, tentatively assigned as N-5 and N-6. Consistent with the individual EM7.2 values obtained, addition of succinate results in the partial reduction of Center N-2, but does not reduce any other centers in the NADH-ubiquinone segment of the respiratory chain. Centers N-2, N-1b, N-3, N-5 and N-6 become almost completely reduced in the presence of NADH, while Centers N-1a and N-4 are only slightly reduced in pigeon heart submitochondrial particles. In pigeon heart mitochondria, the EM7.2 of Center N-4 lies much closer to that of Center N-3, so that resolution of the Center N-3 and N-4 spectra is not feasible in mitochondrial preparations. EM7.2 values and EPR lineshapes for the other iron-sulfur centers of the NADH-ubiquinone segment in the respiratory chain of intact mitochondria are similar to those obtained in submitochondrial particle preparations. Thus, it can be concluded that, in intact pigeon heart mitochondria, at least five iron-sulfur centers show EM7.2 values around minus 250 mV; Center N-2 exhibits a high EM7.2 (minus 20 plus or minus 20 mV), while Center N-1a shows a very low EM7.2 (minus 380 plus or minus 20 mV).", "contents": "Thermodynamic and EPR characterization of iron-sulfur centers in the NADH-ubiquinone segment of the mitochondrial respiratory chain in pigeon heart. Several iron-sulfur centers in the NADH-ubiquinone segment of the respiratory chain in pigeon heart mitochondria and in submitochondrial particles were analyzed by the combined application of cryogenic EPR (between 30 and 4.2 degrees K) and potentiometric titration. Center N-1 (iron-sulfur centers associated with NADH dehydrogenase are designated with the prefix \"N\") resolves into two single electron titratins with EM7.2 values of minus 380 plus or minus 20 mV and minus 240 plus or minus 20 mV (Centers N-1a and N-1b, respectively). Center N-1a exhibits an EPR spectrum of nearly axial symmetry with g parellel = 2.03, g = 1.94, while that of Center N-1b shows more apparent rhombic symmetry with gz = 2.03, gy = 1.94 and gx = 1.91. Center N-2 also reveals EPR signals of axial symmetry at g parallel = 2.05 and g = 1.93 and its principal signal overlaps with those of Centers N-1a and N-1b. Center N-2 can be easily resolved from N-1a and N-1b because of its high EM7.2 value (minus 20 plus or minus 20 mV). Resolution of Centers N-3 and N-4 was achieved potentiometrically in submitochondrial particles. The component with EM7.2 = minus 240 plus or minus 20 mV is defined as Center N-3 (gz = 2.10, (gz = 2.10, (gy = 1.93?), GX = 1.87); the minus 405 plus or minus 20 mV component as Center N-4 (gz = 2.11, (gy = 1.93?), gx = 1.88). At temperatures close to 4.2 degrees K, EPR signals at g = 2.11, 2.06, 2.03, 1.93, 1.90 and 1.88 titrate with EM7.2 = minus 260 plus or minus 20 mV. The multiplicity of peaks suggests the presence of at least two different iron-sulfur centers having similar EM7.2 values (minus 260 plus or minus 20 mV); HENCE, tentatively assigned as N-5 and N-6. Consistent with the individual EM7.2 values obtained, addition of succinate results in the partial reduction of Center N-2, but does not reduce any other centers in the NADH-ubiquinone segment of the respiratory chain. Centers N-2, N-1b, N-3, N-5 and N-6 become almost completely reduced in the presence of NADH, while Centers N-1a and N-4 are only slightly reduced in pigeon heart submitochondrial particles. In pigeon heart mitochondria, the EM7.2 of Center N-4 lies much closer to that of Center N-3, so that resolution of the Center N-3 and N-4 spectra is not feasible in mitochondrial preparations. EM7.2 values and EPR lineshapes for the other iron-sulfur centers of the NADH-ubiquinone segment in the respiratory chain of intact mitochondria are similar to those obtained in submitochondrial particle preparations. Thus, it can be concluded that, in intact pigeon heart mitochondria, at least five iron-sulfur centers show EM7.2 values around minus 250 mV; Center N-2 exhibits a high EM7.2 (minus 20 plus or minus 20 mV), while Center N-1a shows a very low EM7.2 (minus 380 plus or minus 20 mV)."} {"id": "PMID:166671", "title": "A kinetic completion of the cyclic photosynthetic electron pathway of Rhodopseudomonas sphaeroides: cytochrome b-cytochrome c2 oxidation-reduction.", "content": "In Rhodopseudomonas sphaeroides, following a single-turnover flash of light, cytochrome c2 is oxidized by reaction center bacteriochlorophyll, and a cytochrome b is reduced by the primary electron acceptor, probably via ubiquinone. In this report we show that, in the uncoupled state, the rate of re-oxidation of the cytochrome b is identical to the rate of reduction of the cytochrome c2, a kinetic completion of the cyclic photosynthetic electron transport system.", "contents": "A kinetic completion of the cyclic photosynthetic electron pathway of Rhodopseudomonas sphaeroides: cytochrome b-cytochrome c2 oxidation-reduction. In Rhodopseudomonas sphaeroides, following a single-turnover flash of light, cytochrome c2 is oxidized by reaction center bacteriochlorophyll, and a cytochrome b is reduced by the primary electron acceptor, probably via ubiquinone. In this report we show that, in the uncoupled state, the rate of re-oxidation of the cytochrome b is identical to the rate of reduction of the cytochrome c2, a kinetic completion of the cyclic photosynthetic electron transport system."} {"id": "PMID:166672", "title": "Enzyme profiles of mammalian bile.", "content": "The activities of subcellular marker enzymes in bile and liver homogenate from several mammalian species have provided information on the specificity of protein release during bile formation. The presence of significant amounts of the plasma membrane enzymes alkaline phosphodiesterase I and leucyl-beta-naphthylamidase in bile, in addition to alkaline phosphatase and 5'-nucleotidase, and the relative absence of intracellular enzymes lends support to the view that bile salt liberation from the hepatocyte is accompanied by a partial solubilization of the plasma (canalicular) membrane without extensive damage to the whole hepatocyte.", "contents": "Enzyme profiles of mammalian bile. The activities of subcellular marker enzymes in bile and liver homogenate from several mammalian species have provided information on the specificity of protein release during bile formation. The presence of significant amounts of the plasma membrane enzymes alkaline phosphodiesterase I and leucyl-beta-naphthylamidase in bile, in addition to alkaline phosphatase and 5'-nucleotidase, and the relative absence of intracellular enzymes lends support to the view that bile salt liberation from the hepatocyte is accompanied by a partial solubilization of the plasma (canalicular) membrane without extensive damage to the whole hepatocyte."} {"id": "PMID:166674", "title": "Stimulation of ion transport by ascorbic acid through inhibition of 3':5'-cyclic-AMP phosphodiesterase in the corneal epithelium and other tissues.", "content": "Ascorbic acid stimulates active transport of Cl-minus by the isolated intact cornea. The effect is not present in corneas previously stimulated by the theophylline, an inhibitor of 3':5\"-cyclic-AMP phosphodiesterase (EC 3.1.4.17), and vice versa, theophylline has no action after stimulation with ascorbic acid. This indicated inhibition of 3':5'-cyclic-AMP phosphodiesterase by ascorbic acid. Assay of phosphodiesterase using 3-H-labeled cyclid AMP of frog and rabbit corneal epithelial homogenates showed an inhibitory effect of ascorbic acid. Concentration of 5 mM produced 16% inhibition with 20 mM producing 46%. This compares with 58% inhibition by theophylline at 5 mM. Phosphodiesterase activity is mostly soluble in frog corneal epithelium but in rabbit 45% is particulate. Soluble and particulate fractions are inhibited by ascorbate, but in rabbits greater inhibition (50%) was observed in the particulate fraction than in the soluble fraction. Other tissues showed inhibition also: frog retina 12%, rat brain (caudate nucleus) 48%, rabbit brain 14%, rabbit liver 16%. It is concluded that ascorbate produces an increase in cyclic AMP content of corneal epithelium and other tissues by inhibition of 3':5'-cyclic-AMP phosphodiesterase. This action may be one of the main functions of the high ascorbic acid content of ocular tissues and explain some of the effects of high dosis of ascorbate in other systems.", "contents": "Stimulation of ion transport by ascorbic acid through inhibition of 3':5'-cyclic-AMP phosphodiesterase in the corneal epithelium and other tissues. Ascorbic acid stimulates active transport of Cl-minus by the isolated intact cornea. The effect is not present in corneas previously stimulated by the theophylline, an inhibitor of 3':5\"-cyclic-AMP phosphodiesterase (EC 3.1.4.17), and vice versa, theophylline has no action after stimulation with ascorbic acid. This indicated inhibition of 3':5'-cyclic-AMP phosphodiesterase by ascorbic acid. Assay of phosphodiesterase using 3-H-labeled cyclid AMP of frog and rabbit corneal epithelial homogenates showed an inhibitory effect of ascorbic acid. Concentration of 5 mM produced 16% inhibition with 20 mM producing 46%. This compares with 58% inhibition by theophylline at 5 mM. Phosphodiesterase activity is mostly soluble in frog corneal epithelium but in rabbit 45% is particulate. Soluble and particulate fractions are inhibited by ascorbate, but in rabbits greater inhibition (50%) was observed in the particulate fraction than in the soluble fraction. Other tissues showed inhibition also: frog retina 12%, rat brain (caudate nucleus) 48%, rabbit brain 14%, rabbit liver 16%. It is concluded that ascorbate produces an increase in cyclic AMP content of corneal epithelium and other tissues by inhibition of 3':5'-cyclic-AMP phosphodiesterase. This action may be one of the main functions of the high ascorbic acid content of ocular tissues and explain some of the effects of high dosis of ascorbate in other systems."} {"id": "PMID:166675", "title": "Decreased binding of insulin to liver plasma membrane receptors in hereditary diabetic mice.", "content": "The interaction of insulin with its receptors was studied in liver plasma membranes of the young non-obese hereditary diabetic mouse (KK strain). Under identical conditions of preparation and incubation, the membranes of the KK mouse bind only 55-70% as much insulin per mg of protein as those of the control mouse (Swiss albino). Scatchard analysis suggests that this decrease in binding is due to a decrease in the number of receptor sites in the membrane of the diabetic mouse. However, the membranes of diabetic and control mice do not exhibit significant differences in hexosamine and sialic acid contents, enzyme activities, and protein and glycoprotein analysis. The decrease in insulin receptors in the KK mouse seems to correlate with the insulin resistance which they exhibit.", "contents": "Decreased binding of insulin to liver plasma membrane receptors in hereditary diabetic mice. The interaction of insulin with its receptors was studied in liver plasma membranes of the young non-obese hereditary diabetic mouse (KK strain). Under identical conditions of preparation and incubation, the membranes of the KK mouse bind only 55-70% as much insulin per mg of protein as those of the control mouse (Swiss albino). Scatchard analysis suggests that this decrease in binding is due to a decrease in the number of receptor sites in the membrane of the diabetic mouse. However, the membranes of diabetic and control mice do not exhibit significant differences in hexosamine and sialic acid contents, enzyme activities, and protein and glycoprotein analysis. The decrease in insulin receptors in the KK mouse seems to correlate with the insulin resistance which they exhibit."} {"id": "PMID:166676", "title": "Effect of lipid alkyl chain perturbations on the assembly of bacteriophage PM2.", "content": "The lipid-containing bacteriophage PM2 can produce infectious virus in cultures infected at temperatures up to 31.5 degrees C, but not at 34 degrees C. Its host, Pseudomonas BAL-31, grows at 34 degrees C and cultures infected at that temperature undergo lysis. Sucrose-gradient analysis shows that 34 degrees C lysates contain no PM2-like particles. Temperature-shift experiments establish that the thermally sensitive process is late in infection when virus assembly is taking place. Adamantanone, a small hydrophobic molecule that perturbs membrane hydrocarbon zones, prevents the production of infective virus. Concentrations which prevent virus production have no effect on host-cell growth or stability of mature virions. Adamantanone exerts its effects late in the infectious cycle, and lysates amde in its presence contain no PM2-like particles. These experiments, carried out at 25 degrees C, indicate that adamantanone prevents the assembly of stable PM2 virus. Spin-label studies suggest that the lipid alkyl chains of the host-cell membrane are in an \"ordered\" state at temperatures below about 33 degrees C and undergo a transition to a \"disordered\" state above that temperature. Furthermore, the addition of adamantanone perturbs the hydrocarbon zones, producing a greater degree of disorder even below 25 degrees C. Our findings suggest that the cell membrane can function and grow with the lipid alkyl chains in either the \"ordered\" or \"disordered\" state, but that the \"ordered\" state must be maintanined for PM2 assembly to occur.", "contents": "Effect of lipid alkyl chain perturbations on the assembly of bacteriophage PM2. The lipid-containing bacteriophage PM2 can produce infectious virus in cultures infected at temperatures up to 31.5 degrees C, but not at 34 degrees C. Its host, Pseudomonas BAL-31, grows at 34 degrees C and cultures infected at that temperature undergo lysis. Sucrose-gradient analysis shows that 34 degrees C lysates contain no PM2-like particles. Temperature-shift experiments establish that the thermally sensitive process is late in infection when virus assembly is taking place. Adamantanone, a small hydrophobic molecule that perturbs membrane hydrocarbon zones, prevents the production of infective virus. Concentrations which prevent virus production have no effect on host-cell growth or stability of mature virions. Adamantanone exerts its effects late in the infectious cycle, and lysates amde in its presence contain no PM2-like particles. These experiments, carried out at 25 degrees C, indicate that adamantanone prevents the assembly of stable PM2 virus. Spin-label studies suggest that the lipid alkyl chains of the host-cell membrane are in an \"ordered\" state at temperatures below about 33 degrees C and undergo a transition to a \"disordered\" state above that temperature. Furthermore, the addition of adamantanone perturbs the hydrocarbon zones, producing a greater degree of disorder even below 25 degrees C. Our findings suggest that the cell membrane can function and grow with the lipid alkyl chains in either the \"ordered\" or \"disordered\" state, but that the \"ordered\" state must be maintanined for PM2 assembly to occur."} {"id": "PMID:166677", "title": "Requirement of heat and metabolic energy for the expression of inhibitory action of colicin K.", "content": "Escherichia coli B, induced for beta-galactoside permease, can accumulate thio-methyl-beta-galactoside in the cell even at 0 degrees D. At this temperature, cells adsorb colicin K but the adsorbed colicin does not inhibit thiomethyl-beta-galactoside uptake. Inhibition by colicin K is, however, seen at 0 degrees C after exposure of the colicin K-cell complex to a high temperature: a greater degree of inhibition occurs with increasing temperature or duration or exposure. There is a transition point at around 21 degrees C in Arrhenius plots of this colicin K activation reaction. If inhibitors of energy yielding reactions are present during the heat treatment, the inhibitory action of colicin K (as measured by thiomethyl-beta-galactoside uptake after returning the colicin K-cell complex to 0 degrees C and removal of the inhibitors) is prevented. These results indicate that adsorbed colicin K is converted into the active state only in the presence of metabolic energy and that cell surface fluidity appears to be concerned in this process.", "contents": "Requirement of heat and metabolic energy for the expression of inhibitory action of colicin K. Escherichia coli B, induced for beta-galactoside permease, can accumulate thio-methyl-beta-galactoside in the cell even at 0 degrees D. At this temperature, cells adsorb colicin K but the adsorbed colicin does not inhibit thiomethyl-beta-galactoside uptake. Inhibition by colicin K is, however, seen at 0 degrees C after exposure of the colicin K-cell complex to a high temperature: a greater degree of inhibition occurs with increasing temperature or duration or exposure. There is a transition point at around 21 degrees C in Arrhenius plots of this colicin K activation reaction. If inhibitors of energy yielding reactions are present during the heat treatment, the inhibitory action of colicin K (as measured by thiomethyl-beta-galactoside uptake after returning the colicin K-cell complex to 0 degrees C and removal of the inhibitors) is prevented. These results indicate that adsorbed colicin K is converted into the active state only in the presence of metabolic energy and that cell surface fluidity appears to be concerned in this process."} {"id": "PMID:166678", "title": "Altered cell surface glycoproteins in phytohemagglutinin-resistant mutants of Chinese hamster ovary cells.", "content": "Purified membranes from surface-labelled phytohemagglutinin-resistant (Pha(R) and wild-type chinese hamster ovary cells have been analysed by sodium dodecyl sulphate gel electrophoresis. Gel patterns were compared for cells labelled via galactose oxidase and B-3H4 or lactoperoxidase and radioactive iodide. The results suggest that Pha-R cells are altered in the carbohydrate portion of a number of their membrane glycoproteins.", "contents": "Altered cell surface glycoproteins in phytohemagglutinin-resistant mutants of Chinese hamster ovary cells. Purified membranes from surface-labelled phytohemagglutinin-resistant (Pha(R) and wild-type chinese hamster ovary cells have been analysed by sodium dodecyl sulphate gel electrophoresis. Gel patterns were compared for cells labelled via galactose oxidase and B-3H4 or lactoperoxidase and radioactive iodide. The results suggest that Pha-R cells are altered in the carbohydrate portion of a number of their membrane glycoproteins."} {"id": "PMID:166679", "title": "Protection of the active site of mitochondrial malate dehydrogenase from inhibition by potassium tetrachloroplatinate.", "content": "Mitochondrial malate dehydrogenase (L-malate : NAD-+ oxido-reductase, EC 1.1.1.37) was inhibited by potassium tetrachloro platinum (II), K-2PtCl-4, in the presence of varying concentrations of NADH, NAD-+ and L-malate and mixtures of NAD-+ and L-malate. It was observed that NADH is an effective protector of the enzyme from inhibition while both NAD-+ and L-malate are poor protectors. Spectral studies have suggested that the protection afforded by the substrates are accomplished by reaction with specific groups on the enzyme rather than by complexation of the substrates with PtCl-4-2-minus. From the above data it has been concluded that the tetrachloroplatinate ion binds only at the active site and that this site which is effectively protected by NADH, and moderately protected by a NAD-+-L-malate complex probably contains one or more sulfur containing amino acid side chains. It is also proposed that when the tetrachloroplatinate complexes with the enzyme there is some effect, possibly a conformational change, which causes the release of NADH at the allosteric site.", "contents": "Protection of the active site of mitochondrial malate dehydrogenase from inhibition by potassium tetrachloroplatinate. Mitochondrial malate dehydrogenase (L-malate : NAD-+ oxido-reductase, EC 1.1.1.37) was inhibited by potassium tetrachloro platinum (II), K-2PtCl-4, in the presence of varying concentrations of NADH, NAD-+ and L-malate and mixtures of NAD-+ and L-malate. It was observed that NADH is an effective protector of the enzyme from inhibition while both NAD-+ and L-malate are poor protectors. Spectral studies have suggested that the protection afforded by the substrates are accomplished by reaction with specific groups on the enzyme rather than by complexation of the substrates with PtCl-4-2-minus. From the above data it has been concluded that the tetrachloroplatinate ion binds only at the active site and that this site which is effectively protected by NADH, and moderately protected by a NAD-+-L-malate complex probably contains one or more sulfur containing amino acid side chains. It is also proposed that when the tetrachloroplatinate complexes with the enzyme there is some effect, possibly a conformational change, which causes the release of NADH at the allosteric site."} {"id": "PMID:166680", "title": "A rapid purification method of restriction endonucleases from Haemophilus strains.", "content": "A simple and rapid method of purification of restriction endonucleases from different Haemophilus strains is presented. By this method highly purified and stable enzymes can be obtained. Separation of different restriction activities present in the same strain is possible. This method was so far successfully used with Haemophilus influenzae, Haemophilus parainfluenzae and Haemophilus aegyptius strains. The main advantages over previously published procedures reside in the simplication of certain purification steps (for instance the BioGel A 0.5 M filtration is replaced by a hydroxyapatite batch step), elimination of exonuclease activity by fractionation with (NH4) 2SO4, separation of different restriction activities by phosphocellulose chromatography, application of this method to various strains and high purification degree of enzymes.", "contents": "A rapid purification method of restriction endonucleases from Haemophilus strains. A simple and rapid method of purification of restriction endonucleases from different Haemophilus strains is presented. By this method highly purified and stable enzymes can be obtained. Separation of different restriction activities present in the same strain is possible. This method was so far successfully used with Haemophilus influenzae, Haemophilus parainfluenzae and Haemophilus aegyptius strains. The main advantages over previously published procedures reside in the simplication of certain purification steps (for instance the BioGel A 0.5 M filtration is replaced by a hydroxyapatite batch step), elimination of exonuclease activity by fractionation with (NH4) 2SO4, separation of different restriction activities by phosphocellulose chromatography, application of this method to various strains and high purification degree of enzymes."} {"id": "PMID:166681", "title": "Assay for adenylate cyclase and cyclic nucleotide phosphodiesterases and the preparation of high specific activity 32-P-labeled substrates.", "content": "Simple one step assay methods for adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) and cyclic nucleotide phosphodiesterases (3',5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) have been developed. [alpha-32-P] ATP is used as the substrate for adenylate cyclase. Acid-heat destruction of [32-P] ATP remaining after the cyclase reaction followed by Zn-Ba treatment quantitatively leaves cyclic [32-P] AMP in the supernatant essentially free from other 32-P-containing compounds. This assay method requires no corrections for recovery and routinely yields blank values less than 0.03 per cent. If higher sensitivity is desired, a simple 5 min alumina column step can be introduced into the procedure which quantitatively elutes cyclic [32-P] AMP directly into a liquid scintillation vial and lowers the blank values to less than 0.002 per cent. This method is rapid and easily performed, without sacrificing high reliability, specificity, or sensitivity. One step phosphodiesterase assays are easily accomplished using 32-P-labeled cyclic nucleotides as substrates. Descending paper chromatography of the reaction mixture on individual 2 cm wide paper strips gives a complete and quantitative separation of all possible products including [5'-32-P] AMP and [5'-32-P] GMP from their respective 32-P-labeled 3',5'-cyclic nucleotides in 1-2 h. The paper strips are cut, inserted in scintillation vials without scintillant and the 32-P-products determined by Cerenkov counting. Low blank values of less than 0.5 per cent and the use of high specific activity 32-P-labeled cyclic nucleotide substrates make this method the most reliable and most sensitive phosphodiesterase assay described to date. Because of the simplicity, specificity, and high sensitivity obtainable with these assay methods using 32-P-labeled substrates, we have also devised simple conditions for the preparation and purification of [alpha-32-P] ATP, cyclic [32-P] AMP and cyclic [32-P] GMP with specific activities in excess of 100 Ci/mmol. These high specific activity 32-Plabeled cyclic nucleotides are important for these new assay methods and are also useful to follow purification recovery of endogenous cyclic AMP and cyclic GMP from biological materials before protein binding or radioimmunological isotope displacement assays when performed in the femtomole range.", "contents": "Assay for adenylate cyclase and cyclic nucleotide phosphodiesterases and the preparation of high specific activity 32-P-labeled substrates. Simple one step assay methods for adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) and cyclic nucleotide phosphodiesterases (3',5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) have been developed. [alpha-32-P] ATP is used as the substrate for adenylate cyclase. Acid-heat destruction of [32-P] ATP remaining after the cyclase reaction followed by Zn-Ba treatment quantitatively leaves cyclic [32-P] AMP in the supernatant essentially free from other 32-P-containing compounds. This assay method requires no corrections for recovery and routinely yields blank values less than 0.03 per cent. If higher sensitivity is desired, a simple 5 min alumina column step can be introduced into the procedure which quantitatively elutes cyclic [32-P] AMP directly into a liquid scintillation vial and lowers the blank values to less than 0.002 per cent. This method is rapid and easily performed, without sacrificing high reliability, specificity, or sensitivity. One step phosphodiesterase assays are easily accomplished using 32-P-labeled cyclic nucleotides as substrates. Descending paper chromatography of the reaction mixture on individual 2 cm wide paper strips gives a complete and quantitative separation of all possible products including [5'-32-P] AMP and [5'-32-P] GMP from their respective 32-P-labeled 3',5'-cyclic nucleotides in 1-2 h. The paper strips are cut, inserted in scintillation vials without scintillant and the 32-P-products determined by Cerenkov counting. Low blank values of less than 0.5 per cent and the use of high specific activity 32-P-labeled cyclic nucleotide substrates make this method the most reliable and most sensitive phosphodiesterase assay described to date. Because of the simplicity, specificity, and high sensitivity obtainable with these assay methods using 32-P-labeled substrates, we have also devised simple conditions for the preparation and purification of [alpha-32-P] ATP, cyclic [32-P] AMP and cyclic [32-P] GMP with specific activities in excess of 100 Ci/mmol. These high specific activity 32-Plabeled cyclic nucleotides are important for these new assay methods and are also useful to follow purification recovery of endogenous cyclic AMP and cyclic GMP from biological materials before protein binding or radioimmunological isotope displacement assays when performed in the femtomole range."} {"id": "PMID:166682", "title": "Stimulation by ATP of alkaline phosphatase in placental plasma membranes.", "content": "1. ATP stimulated the p-nitrophenyl phosphatase activity of placental plasma membranes, with an increase in activity of approximately 100% at 5 mM ATP. The stimulation was not dependent on the presence of Mg-2-+. 2. The K-m for p-nitrophenyl phosphate was not changed by the presence of 5 mM ATP. 3. ATP hydrolysis by the plasma membrane preparation under the same assay conditions as for alkaline phosphatase was not influenced by the presence of 5 mM p-nitrophenyl phosphate. 4. Extraction of the plasma membrane preparation with n-butanol abolished the stimulatory effect of ATP, as well as Ca-2-+-activated ATPase activity.", "contents": "Stimulation by ATP of alkaline phosphatase in placental plasma membranes. 1. ATP stimulated the p-nitrophenyl phosphatase activity of placental plasma membranes, with an increase in activity of approximately 100% at 5 mM ATP. The stimulation was not dependent on the presence of Mg-2-+. 2. The K-m for p-nitrophenyl phosphate was not changed by the presence of 5 mM ATP. 3. ATP hydrolysis by the plasma membrane preparation under the same assay conditions as for alkaline phosphatase was not influenced by the presence of 5 mM p-nitrophenyl phosphate. 4. Extraction of the plasma membrane preparation with n-butanol abolished the stimulatory effect of ATP, as well as Ca-2-+-activated ATPase activity."} {"id": "PMID:166683", "title": "Effect of adenine nucleotides on NAD-dependent isocitrate dehydrogenases in rhizobia and bacteroids of legume root nodules.", "content": "ATP, ADP, AMP and cyclic AMP inhibit NAD-dependent isocitrate dehydrogenase (L-s-isocitrate : NAD-+ oxidoreductase, EC 1.1.1.41) from rhizobia but have no effect on the enzyme from corresponding bacteroids. This was observed using three rhizobial strains two of which are effective, and one ineffective, with Lotus pedunculatus. Using partially purified enzyme from each of the three rhizobial strains it was found that the adenine nucleotides inhibit the enzyme by competing with NAD-+, not with isocritrate. The rate of reaction catalysed by the enzyme (expressed as activity per mg protein) in cell-free extracts of each of the effective rhizobial strains was about three times that of the reaction in extracts of the corresponding bacteroids. No correlation was found between effectiveness and NAD-dependent isocitrate dehydrogenase activity in the rhizobial cells.", "contents": "Effect of adenine nucleotides on NAD-dependent isocitrate dehydrogenases in rhizobia and bacteroids of legume root nodules. ATP, ADP, AMP and cyclic AMP inhibit NAD-dependent isocitrate dehydrogenase (L-s-isocitrate : NAD-+ oxidoreductase, EC 1.1.1.41) from rhizobia but have no effect on the enzyme from corresponding bacteroids. This was observed using three rhizobial strains two of which are effective, and one ineffective, with Lotus pedunculatus. Using partially purified enzyme from each of the three rhizobial strains it was found that the adenine nucleotides inhibit the enzyme by competing with NAD-+, not with isocritrate. The rate of reaction catalysed by the enzyme (expressed as activity per mg protein) in cell-free extracts of each of the effective rhizobial strains was about three times that of the reaction in extracts of the corresponding bacteroids. No correlation was found between effectiveness and NAD-dependent isocitrate dehydrogenase activity in the rhizobial cells."} {"id": "PMID:166684", "title": "Comparative structural studies of the active site of ATP: guanidine phosphotransferases. The essential cysteine tryptic peptide of taurocyamine kinase from Arenicola marina.", "content": "The active cysteinyl residues of dimeric taurocyamine kinase from Arenicola marina were labelled with N-ethyl-[1-14C]maleimide. The resulting inactivated N-ethyl-[1-14C]succinimido enzyme was then subjected to tryptic hydrolysis. The peptide containing the labelled essential cysteinyl residue was isolated. The amino acid sequence of this peptide is Leu-Gly-Tyr-Leu-Gly-Thr-[14C]-Cys-Pro-Thr-Asn-Ile-Gly-Leu-Arg. This sequence is very similar to that of homologous ATP:guanidine phosphotransferases previously studied, arginine kinase from Homarus vulgaris muscle, creatine kinase from ox brain and ox muscle, and from rabbit muscle, and lombricine kinase from Lubricus terrestris.", "contents": "Comparative structural studies of the active site of ATP: guanidine phosphotransferases. The essential cysteine tryptic peptide of taurocyamine kinase from Arenicola marina. The active cysteinyl residues of dimeric taurocyamine kinase from Arenicola marina were labelled with N-ethyl-[1-14C]maleimide. The resulting inactivated N-ethyl-[1-14C]succinimido enzyme was then subjected to tryptic hydrolysis. The peptide containing the labelled essential cysteinyl residue was isolated. The amino acid sequence of this peptide is Leu-Gly-Tyr-Leu-Gly-Thr-[14C]-Cys-Pro-Thr-Asn-Ile-Gly-Leu-Arg. This sequence is very similar to that of homologous ATP:guanidine phosphotransferases previously studied, arginine kinase from Homarus vulgaris muscle, creatine kinase from ox brain and ox muscle, and from rabbit muscle, and lombricine kinase from Lubricus terrestris."} {"id": "PMID:166685", "title": "Cyclic AMP binding proteins in early embryos of Drosophila melanogaster.", "content": "A variety of effects of cyclic AMP on cellular and subcellular phenomena suggest that there may be other modes of action of cyclic AMP then activation of protein kinase. It is also known that developing embryos contain cyclic AMP and its related enzymes. In order to explore the role of cyclic AMP in embryogenesis, a survey of proteins capable of binding cyclic AMP in the embryonic supernatant of Drosophila melanogaster was carried out. As the result, two cyclic AMP-binding proteins were found and characterized. The one (L) is, as expected, associated with protein kinase and has a dissociation constant of about 10(-9) M. Its molecular weight of 21 000 daltons is extremely small when compared with similar proteins in other organisms. The other (H), whose function is yet to be found, has a molecular weight of about 200 000 daltons and has a dissociation constant of about 10-7 M. Some laxity in binding specificity of the latter protein among adenosine nucleotides was observed, but cyclic AMP is the strongest ligand among them.", "contents": "Cyclic AMP binding proteins in early embryos of Drosophila melanogaster. A variety of effects of cyclic AMP on cellular and subcellular phenomena suggest that there may be other modes of action of cyclic AMP then activation of protein kinase. It is also known that developing embryos contain cyclic AMP and its related enzymes. In order to explore the role of cyclic AMP in embryogenesis, a survey of proteins capable of binding cyclic AMP in the embryonic supernatant of Drosophila melanogaster was carried out. As the result, two cyclic AMP-binding proteins were found and characterized. The one (L) is, as expected, associated with protein kinase and has a dissociation constant of about 10(-9) M. Its molecular weight of 21 000 daltons is extremely small when compared with similar proteins in other organisms. The other (H), whose function is yet to be found, has a molecular weight of about 200 000 daltons and has a dissociation constant of about 10-7 M. Some laxity in binding specificity of the latter protein among adenosine nucleotides was observed, but cyclic AMP is the strongest ligand among them."} {"id": "PMID:166686", "title": "Studies on the composition of pig serum lipoproteins. Isolation and characterization of different apoproteins.", "content": "1. Different lipoprotein density fractions from pig serum were isolated by phosphotungstate precipitation followed by purification in the preparative ultra-centrifuge. 2. The protein part of very low density lipoproteins was composed of approximately 52 percent lipoprotein B apoprotein and the rest of lipoprotein C II apoprotein and other as yet unidentified peptides. 3. The protein moiety of low density lipoproteins consisted primarily of lipoprotein B apoprotein (over 95 percent); the amino acid compositions of lipoprotein B apoprotein of very low and low density lipoproteins were practically identical. 4. The predominant polypeptide of pig serum high density lipoproteins exhibited an amino acid composition and a molecular weight very similar to human liprotein A I apoprotein. In contrast to human lipoprotein A I apoprotein, the apoprotein from pigs was found to release leucine first followed by alanine, threonine, and lysine upon incubation with carboxypeptidase A. 5. In pig serum the major lipoprotein C apoprotein was found to be a polypeptide similar in amino acid composition to lipoprotein C II apoprotein from human serum. The molecular weight of this polypeptide is approximately 8000. Incubation experiments with carboxypeptidase A indicate serine to be the most likely C-terminal amino acid.", "contents": "Studies on the composition of pig serum lipoproteins. Isolation and characterization of different apoproteins. 1. Different lipoprotein density fractions from pig serum were isolated by phosphotungstate precipitation followed by purification in the preparative ultra-centrifuge. 2. The protein part of very low density lipoproteins was composed of approximately 52 percent lipoprotein B apoprotein and the rest of lipoprotein C II apoprotein and other as yet unidentified peptides. 3. The protein moiety of low density lipoproteins consisted primarily of lipoprotein B apoprotein (over 95 percent); the amino acid compositions of lipoprotein B apoprotein of very low and low density lipoproteins were practically identical. 4. The predominant polypeptide of pig serum high density lipoproteins exhibited an amino acid composition and a molecular weight very similar to human liprotein A I apoprotein. In contrast to human lipoprotein A I apoprotein, the apoprotein from pigs was found to release leucine first followed by alanine, threonine, and lysine upon incubation with carboxypeptidase A. 5. In pig serum the major lipoprotein C apoprotein was found to be a polypeptide similar in amino acid composition to lipoprotein C II apoprotein from human serum. The molecular weight of this polypeptide is approximately 8000. Incubation experiments with carboxypeptidase A indicate serine to be the most likely C-terminal amino acid."} {"id": "PMID:166687", "title": "Paramagnetic spin label interactions with the envelope of a group A arbovirus. Lipid organization.", "content": "Electron paramagnetic resonance observations were made on nitroxide spin- labeled molecules which were bound to the TC-83 vaccine strain of Venezuelan equine-encephalomyelitis virus. Paramagnetic resonance parameters derived from the observations and their dependence on sample temperature were similar but not identical to those which have been reported for these labels dissolved in lipid bilayer membranes of mammalian and bacterial origin. The data has a mechanical rigidity substantially greater than that of bilayers in cellular membranes. A model is presented which assumes the location of the lipid bilayer outside the nucleoprotein capsid and inside a spherical layer of envelope proteins. The model is in accord with Harrison's X-ray diffraction results for Sindbis virus. The model is discussed in terms of its implications with respects to the role played by lipid in viral maturation and infectivity.", "contents": "Paramagnetic spin label interactions with the envelope of a group A arbovirus. Lipid organization. Electron paramagnetic resonance observations were made on nitroxide spin- labeled molecules which were bound to the TC-83 vaccine strain of Venezuelan equine-encephalomyelitis virus. Paramagnetic resonance parameters derived from the observations and their dependence on sample temperature were similar but not identical to those which have been reported for these labels dissolved in lipid bilayer membranes of mammalian and bacterial origin. The data has a mechanical rigidity substantially greater than that of bilayers in cellular membranes. A model is presented which assumes the location of the lipid bilayer outside the nucleoprotein capsid and inside a spherical layer of envelope proteins. The model is in accord with Harrison's X-ray diffraction results for Sindbis virus. The model is discussed in terms of its implications with respects to the role played by lipid in viral maturation and infectivity."} {"id": "PMID:166688", "title": "Sulphate transport by rat ileum. Effect of molybdate and other anions.", "content": "Kinetic constants for SO4-2- transport by upper and lower rat ileum in vitro have been determined by computer fitting of rate vs concentration data obtained using the everted sac technique. MoO-4-2- inhibition of this transport is competitive, and kinetic constants for the inhibition were similarly determined. Transport is also inhibited by the anions WO4-2-, S2O3-2- and SeO4-2-, in the order S2O3-2- greater than SeO4-2- greater than or equal to MoO4-2- greater than WO4-2-. These anions have no effect on the transport of L-valine. Low SO4-2- transport rates were observed in sacs from animals fed a high-molybdenum diet. The significance of the results with respect to the problem of molybdate toxicity in animals is discussed, and related to the known protective effect of SO4-2-.", "contents": "Sulphate transport by rat ileum. Effect of molybdate and other anions. Kinetic constants for SO4-2- transport by upper and lower rat ileum in vitro have been determined by computer fitting of rate vs concentration data obtained using the everted sac technique. MoO-4-2- inhibition of this transport is competitive, and kinetic constants for the inhibition were similarly determined. Transport is also inhibited by the anions WO4-2-, S2O3-2- and SeO4-2-, in the order S2O3-2- greater than SeO4-2- greater than or equal to MoO4-2- greater than WO4-2-. These anions have no effect on the transport of L-valine. Low SO4-2- transport rates were observed in sacs from animals fed a high-molybdenum diet. The significance of the results with respect to the problem of molybdate toxicity in animals is discussed, and related to the known protective effect of SO4-2-."} {"id": "PMID:166689", "title": "Investigations of thermotropic phase changes in peripheral nerve of frog and rat. A spin label study.", "content": "The temperature-dependent fluidity of myelin of frog and rat peripheral nerve (Nervus ischiadicus) was studied using the spin label technique. In frog nerve a phase change was detected at 38 degree C. In rat nerve no sharp phase change could be established, and the lipid-depleted frog and rat nerve also showed no transition. From the spectral data, it was concluded that in frog and rat nerve the lipid-protein interactions are different, i.e. species dependent. Ca-2+-depletion of frog nerve caused a loss of transition, while rat nerve remained unaffected. Thus it was indicated that, in frog nerve, Ca-2+ is involved in the phase change. In the total lipid extract of frog nerve a phase change centered at 32 degree C occurred, while the total lipid extract of rat nerve again showed no transition. It is suggested that a connexion exists between our results and investigations on the temperature dependence of an axonal conduction block of nerve.", "contents": "Investigations of thermotropic phase changes in peripheral nerve of frog and rat. A spin label study. The temperature-dependent fluidity of myelin of frog and rat peripheral nerve (Nervus ischiadicus) was studied using the spin label technique. In frog nerve a phase change was detected at 38 degree C. In rat nerve no sharp phase change could be established, and the lipid-depleted frog and rat nerve also showed no transition. From the spectral data, it was concluded that in frog and rat nerve the lipid-protein interactions are different, i.e. species dependent. Ca-2+-depletion of frog nerve caused a loss of transition, while rat nerve remained unaffected. Thus it was indicated that, in frog nerve, Ca-2+ is involved in the phase change. In the total lipid extract of frog nerve a phase change centered at 32 degree C occurred, while the total lipid extract of rat nerve again showed no transition. It is suggested that a connexion exists between our results and investigations on the temperature dependence of an axonal conduction block of nerve."} {"id": "PMID:166690", "title": "The optical activity of D-erythro-sphingomyelin and its contribution to the circular dichroism of sphingomyelin-containing systems.", "content": "Circular dichroism studies on bovine brain sphingomyelin show the presence of a strong negative cotton effect below 200 nm, the position and magnitude of which depend on the physical state of the lipid. This cotton effect is thought to arise from the pi-pi transition of the amide group in the sphingomyelin backbone. The sphingomyelin contribution to the observed ellipticity of membranes and lipoprotein complexes depends on the mol fraction of amide groups present as sphingomyelin: this contribution is calculated to be less than 2% in the case of serum high density lipoprotein and the order of 20% below 200 nm in the case of the erythrocyte ghost membrane. Due to the similarity of the CD spectrum of sphingomyelin to that of a random coil polypeptide, use of uncorrected ellipticity data is expected to lead to an overestimate of the random coil content of proteins in systems containing a high sphingomyelin content.", "contents": "The optical activity of D-erythro-sphingomyelin and its contribution to the circular dichroism of sphingomyelin-containing systems. Circular dichroism studies on bovine brain sphingomyelin show the presence of a strong negative cotton effect below 200 nm, the position and magnitude of which depend on the physical state of the lipid. This cotton effect is thought to arise from the pi-pi transition of the amide group in the sphingomyelin backbone. The sphingomyelin contribution to the observed ellipticity of membranes and lipoprotein complexes depends on the mol fraction of amide groups present as sphingomyelin: this contribution is calculated to be less than 2% in the case of serum high density lipoprotein and the order of 20% below 200 nm in the case of the erythrocyte ghost membrane. Due to the similarity of the CD spectrum of sphingomyelin to that of a random coil polypeptide, use of uncorrected ellipticity data is expected to lead to an overestimate of the random coil content of proteins in systems containing a high sphingomyelin content."} {"id": "PMID:166691", "title": "Spin label evidence for the role of lysoglycerophosphatides in cellular membranes of hibernating mammals.", "content": "The phospholipid composition of ground squirrel heart muscle changes during hibernation: more lysoglycerophosphatides are found in the hibernating state than in the active state. Phase transitions inferred from spin label motion occur in the usual manner typical of mammalian mitochondria for the mitochondria and mitochondrial lipids from active squirrels. However, a conspicuous absence of a spin label-detectable phase transition is observed in equivalent preparations from hibernating animals. The addition of lysolecithin to preparations from active squirrels removes the break and induces a straight line in the Arrhenius plot. The lack of a spin label-detectable phase transition in hibernating animals, therefore, is attributed to an increased content of lysoglycerophosphatides present in the phospholipids during hibernation.", "contents": "Spin label evidence for the role of lysoglycerophosphatides in cellular membranes of hibernating mammals. The phospholipid composition of ground squirrel heart muscle changes during hibernation: more lysoglycerophosphatides are found in the hibernating state than in the active state. Phase transitions inferred from spin label motion occur in the usual manner typical of mammalian mitochondria for the mitochondria and mitochondrial lipids from active squirrels. However, a conspicuous absence of a spin label-detectable phase transition is observed in equivalent preparations from hibernating animals. The addition of lysolecithin to preparations from active squirrels removes the break and induces a straight line in the Arrhenius plot. The lack of a spin label-detectable phase transition in hibernating animals, therefore, is attributed to an increased content of lysoglycerophosphatides present in the phospholipids during hibernation."} {"id": "PMID:166692", "title": "Studies on the regulation of the concentration of androgens and androgen receptors in nuclei of prostatic cells.", "content": "Experiments were performed to assess the effect of intracellular androgen metabolism and the availability of cytoplasmic receptors on the concentration of androgens and androgen receptors in nuclei of prostatic cells. It was found that androgens are incorporated into the nucleus by a regulated, selective process which appears to limit the type and amount of androgen transported across the nuclear membrane. The metabolic conversion of testosterone to dihydrotestosterone which takes place in cytoplasm does not reduce transport and, very likely, affects only the ratio of testosterone and dihydrotestosterone transferred into the nucleus. In vivo, when the intranuclear concentration of androgens approaches 250 nM (8 pmol per mg DNA), an apparent concentration ceiling is reached even in the presence of a downward concentration gradient that would be expected to promote further transport across the nuclear membrane. This finding strongly suggests that in vivo the nuclear membrane acts as a barrier to the passage of androgens and, therefore, mitigates against the possibility that passive diffusion is an important mechanism of afferent transport of androgens into the nucleus. The ability of the nucleus to concentrate testosterone and dihydrotestosterone was clearly demonstrated in vivo when cytoplasmic concentrations of androgens of approximately 20 nM were accompanied by intranuclear concentrations in the vicinity of 250 nM. Since the measured concentration of testosterone and dihydrotestosterone in prostate of several species fall within the 5-20 nM range, it is evident that androgen concentrations in the nucleus as high as 250 nM may be typical of the physiological steady state. At the latter concentration the nucleus contains 60 000 androgen molecules: in approximate terms one third of this total is bound to a large molecular weight component of the nucleus, one third is bound to a 3.3 S receptor and one third is free or loosely bound. Since 60 000 androgen molecules and 20 000 receptor molecules appear in the nucleus before transport stops, it seems that the quantity of 4.4 S cytoplasmic receptor estimated at 174 plus or minus 24 pmol per mg protein (equivalent to about 8000 molecules per cell) is insufficient to account for the total influx of androgens and androgen receptors into the nucleus. Thus, although these results support the view that cytoplasmic receptors and the capacity to transport androgens are closely linked phenotypic markers of intracellular steroid hormone action, they suggest that the control of androgen concentration in the nucleus is achieved in a more intricate fashion than simply through a dependence on the presumed translocation of 4.4 S androgen-receptor complex into the nucleus.", "contents": "Studies on the regulation of the concentration of androgens and androgen receptors in nuclei of prostatic cells. Experiments were performed to assess the effect of intracellular androgen metabolism and the availability of cytoplasmic receptors on the concentration of androgens and androgen receptors in nuclei of prostatic cells. It was found that androgens are incorporated into the nucleus by a regulated, selective process which appears to limit the type and amount of androgen transported across the nuclear membrane. The metabolic conversion of testosterone to dihydrotestosterone which takes place in cytoplasm does not reduce transport and, very likely, affects only the ratio of testosterone and dihydrotestosterone transferred into the nucleus. In vivo, when the intranuclear concentration of androgens approaches 250 nM (8 pmol per mg DNA), an apparent concentration ceiling is reached even in the presence of a downward concentration gradient that would be expected to promote further transport across the nuclear membrane. This finding strongly suggests that in vivo the nuclear membrane acts as a barrier to the passage of androgens and, therefore, mitigates against the possibility that passive diffusion is an important mechanism of afferent transport of androgens into the nucleus. The ability of the nucleus to concentrate testosterone and dihydrotestosterone was clearly demonstrated in vivo when cytoplasmic concentrations of androgens of approximately 20 nM were accompanied by intranuclear concentrations in the vicinity of 250 nM. Since the measured concentration of testosterone and dihydrotestosterone in prostate of several species fall within the 5-20 nM range, it is evident that androgen concentrations in the nucleus as high as 250 nM may be typical of the physiological steady state. At the latter concentration the nucleus contains 60 000 androgen molecules: in approximate terms one third of this total is bound to a large molecular weight component of the nucleus, one third is bound to a 3.3 S receptor and one third is free or loosely bound. Since 60 000 androgen molecules and 20 000 receptor molecules appear in the nucleus before transport stops, it seems that the quantity of 4.4 S cytoplasmic receptor estimated at 174 plus or minus 24 pmol per mg protein (equivalent to about 8000 molecules per cell) is insufficient to account for the total influx of androgens and androgen receptors into the nucleus. Thus, although these results support the view that cytoplasmic receptors and the capacity to transport androgens are closely linked phenotypic markers of intracellular steroid hormone action, they suggest that the control of androgen concentration in the nucleus is achieved in a more intricate fashion than simply through a dependence on the presumed translocation of 4.4 S androgen-receptor complex into the nucleus."} {"id": "PMID:166693", "title": "The control of anaerobic glycolysis by glucose transport and ouabain in slices of hepatoma 3924A.", "content": "1. The activities of glycolysis and K-+ transport have been studied in slices of Morris hepatoma 3924A incubated under anaerobic conditions in the presence of different concentrations of glucose (1-50 mM). 2. Ouabain-sensitive net transport of K-+ was observed at all glucose concentrations greater than 1 mM; ouabain reduced the rate of glycolysis by about 25% at all glucose concentrations able to support ion transport. 3. The net entry of glucose into the intracellular phase was studied at varying glucose concentrations. The rate of glucose entry was similar to the rate of glucose utilisation by anaerobic glycolysis at medium concentrations of 10 mM and less, but exceeded the rate of glycolysis at 20 mM and above. 4. The glucose entry was not Na-+-dependent and was not inhibited by ouabain. 5. The results suggest (a) that the reduction in glycolytic activity caused by ouabain is not due to an inhibition of glucose transport and (b) that the glucose transport system of this poorly differentiated hepatoma has properties similar to that of normal liver.", "contents": "The control of anaerobic glycolysis by glucose transport and ouabain in slices of hepatoma 3924A. 1. The activities of glycolysis and K-+ transport have been studied in slices of Morris hepatoma 3924A incubated under anaerobic conditions in the presence of different concentrations of glucose (1-50 mM). 2. Ouabain-sensitive net transport of K-+ was observed at all glucose concentrations greater than 1 mM; ouabain reduced the rate of glycolysis by about 25% at all glucose concentrations able to support ion transport. 3. The net entry of glucose into the intracellular phase was studied at varying glucose concentrations. The rate of glucose entry was similar to the rate of glucose utilisation by anaerobic glycolysis at medium concentrations of 10 mM and less, but exceeded the rate of glycolysis at 20 mM and above. 4. The glucose entry was not Na-+-dependent and was not inhibited by ouabain. 5. The results suggest (a) that the reduction in glycolytic activity caused by ouabain is not due to an inhibition of glucose transport and (b) that the glucose transport system of this poorly differentiated hepatoma has properties similar to that of normal liver."} {"id": "PMID:166694", "title": "Chaotropic anions and the surface potential of bilayer membranes.", "content": "The chaotropic anions perchlorate and thiocyanate adsorb to artificial phospholipid membranes. The negative electrostatic potential they produce at the surface of the membranes was measured by two independent techniques. The conductance produced by neutral carriers of cations and anions was measured to estimate changes in the surface potentials of planar black lipid films and the electrophoretic mobility of phospholipid vesicles was used to monitor changes in the zeta potentials of spherical bilayer membranes. Qualitatively similar results were obtained with the two techniques. The results, moreover, agreed with the change in surface potential produced by these anions at an air water interface, as measured directly with an ionizing electrode (Randles, J. E. B. (1957) Discuss. Faraday Soc. 24, 194-199). The results obtained with artificial bilayers may explain the observation (Wieth, J. O. (1970) J. Physiol. 207, 581-609) that thiocyanate increases the sodium or potassium and decreases the sulfate permeability of erythrocyte membranes.", "contents": "Chaotropic anions and the surface potential of bilayer membranes. The chaotropic anions perchlorate and thiocyanate adsorb to artificial phospholipid membranes. The negative electrostatic potential they produce at the surface of the membranes was measured by two independent techniques. The conductance produced by neutral carriers of cations and anions was measured to estimate changes in the surface potentials of planar black lipid films and the electrophoretic mobility of phospholipid vesicles was used to monitor changes in the zeta potentials of spherical bilayer membranes. Qualitatively similar results were obtained with the two techniques. The results, moreover, agreed with the change in surface potential produced by these anions at an air water interface, as measured directly with an ionizing electrode (Randles, J. E. B. (1957) Discuss. Faraday Soc. 24, 194-199). The results obtained with artificial bilayers may explain the observation (Wieth, J. O. (1970) J. Physiol. 207, 581-609) that thiocyanate increases the sodium or potassium and decreases the sulfate permeability of erythrocyte membranes."} {"id": "PMID:166695", "title": "Selective excision of gamma ray damaged thymine from the DNA of cultured mammalian cells.", "content": "Three mammalian cell lines (WI-38, SV40-transformed WI-38 and Chinese hamster ovary) were exposed to high doses of 137-Cs gamma rays and their DNA analysed, following various periods of postirradiation incubation, for products of the 5,6-dihydroxy-dihydrothymine type. Within fifteen minutes of incubation at 37 degrees C 70 to 90 percent of these radiation products were removed from acid-precipitable material in all three cell lines. The amount of DNA degradation induced by radiation varied from approximately one percent in WI-38 cells to 15 percent in SV40-transformed WI-38 cells. Comparison of DNA degradation with the amount of thymine radiation product removed indicates that a selective gamma ray-induced excision repair capability exists in mammalian cells. Because of its more rapid kinetics, gamma ray excision repair is probably a distinct process as compared with ultraviolet-induced pyrimidine dimer excision.", "contents": "Selective excision of gamma ray damaged thymine from the DNA of cultured mammalian cells. Three mammalian cell lines (WI-38, SV40-transformed WI-38 and Chinese hamster ovary) were exposed to high doses of 137-Cs gamma rays and their DNA analysed, following various periods of postirradiation incubation, for products of the 5,6-dihydroxy-dihydrothymine type. Within fifteen minutes of incubation at 37 degrees C 70 to 90 percent of these radiation products were removed from acid-precipitable material in all three cell lines. The amount of DNA degradation induced by radiation varied from approximately one percent in WI-38 cells to 15 percent in SV40-transformed WI-38 cells. Comparison of DNA degradation with the amount of thymine radiation product removed indicates that a selective gamma ray-induced excision repair capability exists in mammalian cells. Because of its more rapid kinetics, gamma ray excision repair is probably a distinct process as compared with ultraviolet-induced pyrimidine dimer excision."} {"id": "PMID:166696", "title": "Polynucleotide duplexes based on poly(7-deazaadenylic acid).", "content": "In order to find a poly(A)-poly(U) analog which could not form a triple-stranded complex and which would have a sufficiently high thermal stability to survive under physiological conditions, the interaction of poly(7-deazaadenylic acid) (poly(c-7A)) with modified polyuridylic acids was examined. Mixing curves constructed by the method of continuous variation, isosbestic points and thermal melting profiles proved that poly(c-7A) formed only 1:1 complex with polyribothymidylic acid and poly(5-bromouridylic acid) (Tm values of 50 and 72 degrees C respectively, in 0.15 M NaCl, 0.01 M KH2 PO4, 0.001 M MgCl2, pH7). In addition poly(c-7A) formed a 1:1 complex with poly(I) (Tm equals 22 degrees C in 0.46 M salt, pH 7), and presumed duplexes were observed in the interaction of poly(c-7A) with poly(dT), poly(2'-azido-2'-deoxyuridylic acid) and poly(2'-O-methyluridylic acid) (Tm values of 35, 32 and 41 degrees C respectively, in 0.10 M NaCl, pH7).", "contents": "Polynucleotide duplexes based on poly(7-deazaadenylic acid). In order to find a poly(A)-poly(U) analog which could not form a triple-stranded complex and which would have a sufficiently high thermal stability to survive under physiological conditions, the interaction of poly(7-deazaadenylic acid) (poly(c-7A)) with modified polyuridylic acids was examined. Mixing curves constructed by the method of continuous variation, isosbestic points and thermal melting profiles proved that poly(c-7A) formed only 1:1 complex with polyribothymidylic acid and poly(5-bromouridylic acid) (Tm values of 50 and 72 degrees C respectively, in 0.15 M NaCl, 0.01 M KH2 PO4, 0.001 M MgCl2, pH7). In addition poly(c-7A) formed a 1:1 complex with poly(I) (Tm equals 22 degrees C in 0.46 M salt, pH 7), and presumed duplexes were observed in the interaction of poly(c-7A) with poly(dT), poly(2'-azido-2'-deoxyuridylic acid) and poly(2'-O-methyluridylic acid) (Tm values of 35, 32 and 41 degrees C respectively, in 0.10 M NaCl, pH7)."} {"id": "PMID:166697", "title": "Stimulation of nuclear poly (adenosine diphosphate-ribose) polymerase activity from HeLa cells by endonucleases.", "content": "Isolated nuclei from HeLa cells can incorporate labeled ADP-ribose from NAD into an acid-precipitable product, poly(ADP-ribose). This reaction is stimulated by 4-6-fold by the addition of deoxyribonuclease I to the complete reaction mixture. If the nuclei are treated first with deoxyribonuclease I, no effect is seen; the stimulation is only apparent when the two enzymes deoxyribonuclease I and poly(ADP-ribose) polymerase, are operating at the same time. After making several minor modifications in the assay mixture, it was found that another endonuclease, micrococcal nuclease, can also stimulate the poly(ADP-ribose) polymerase activity of HeLa nuclei. A comparison of the two stimulatory effects indicated that the two endonucleases activated to the poly(ADP-ribose) polymerase activity of HeLa nuclei in the same way. Overall this evidence suggests that poly(ADP-ribose) polymerase may have a functional role in the process of DNA repair.", "contents": "Stimulation of nuclear poly (adenosine diphosphate-ribose) polymerase activity from HeLa cells by endonucleases. Isolated nuclei from HeLa cells can incorporate labeled ADP-ribose from NAD into an acid-precipitable product, poly(ADP-ribose). This reaction is stimulated by 4-6-fold by the addition of deoxyribonuclease I to the complete reaction mixture. If the nuclei are treated first with deoxyribonuclease I, no effect is seen; the stimulation is only apparent when the two enzymes deoxyribonuclease I and poly(ADP-ribose) polymerase, are operating at the same time. After making several minor modifications in the assay mixture, it was found that another endonuclease, micrococcal nuclease, can also stimulate the poly(ADP-ribose) polymerase activity of HeLa nuclei. A comparison of the two stimulatory effects indicated that the two endonucleases activated to the poly(ADP-ribose) polymerase activity of HeLa nuclei in the same way. Overall this evidence suggests that poly(ADP-ribose) polymerase may have a functional role in the process of DNA repair."} {"id": "PMID:166698", "title": "[Interaction of rhodopsin with quinone].", "content": "The reaction of rodopsin extracted with cetyltrimethylammonium bromide with p-benzoquinone was studied with spectrophotometric and ESR methods. In the dark quinone reacted with three SH-groups of rodopsin, in the light with three more SH- and two unknown groups of decolourized rodopsin. The interaction of quinone with SH-groups liberated under light effect on rodopsin proceeds with the formation of intermediate free-radical products.", "contents": "[Interaction of rhodopsin with quinone]. The reaction of rodopsin extracted with cetyltrimethylammonium bromide with p-benzoquinone was studied with spectrophotometric and ESR methods. In the dark quinone reacted with three SH-groups of rodopsin, in the light with three more SH- and two unknown groups of decolourized rodopsin. The interaction of quinone with SH-groups liberated under light effect on rodopsin proceeds with the formation of intermediate free-radical products."} {"id": "PMID:166699", "title": "[EPR study of the mechanism of photooxidation of chlorophyll a by nitro compounds].", "content": "An ESR signal with g-value of 2,0026 and peak-to-peak with 8,5 Oe was observed in ethanole solutions of chlorophill a and nitroderivatives of naphtalene under red light illumination. The ESR signal consisted of chlorophyll cation radical resonance, superimposed on an nitronaphtalene anion radical. Less than the ratio greater than between the quantities of these radicals and the character of decay kinetics are influenced by the medium acidity. An analysis of kinetic curves is performed, and the effect of the medium acidity on the mechanism of one-electron transfer reaction between chlorophyll and nitronaphtalene molecules is explained.", "contents": "[EPR study of the mechanism of photooxidation of chlorophyll a by nitro compounds]. An ESR signal with g-value of 2,0026 and peak-to-peak with 8,5 Oe was observed in ethanole solutions of chlorophill a and nitroderivatives of naphtalene under red light illumination. The ESR signal consisted of chlorophyll cation radical resonance, superimposed on an nitronaphtalene anion radical. Less than the ratio greater than between the quantities of these radicals and the character of decay kinetics are influenced by the medium acidity. An analysis of kinetic curves is performed, and the effect of the medium acidity on the mechanism of one-electron transfer reaction between chlorophyll and nitronaphtalene molecules is explained."} {"id": "PMID:166700", "title": "[Pharamagnetic centers developing during irradiation of gamma-phos].", "content": "The ESR spectra's of X-irradiated radioprotector gamma-phos have been studied. Using the analysis of relaxation effects in this sample irradiated at room temperature three paramagnetic centers have been discovered. One of these centers is classed with the free radical approximately CH2--CH--CH2 approximately (R1)-G(R1) value decreases with a decrease of irradiation temperature. Free radicals R1 are not oxidized in the air. Two other of paramagnetic centers have not been identified.", "contents": "[Pharamagnetic centers developing during irradiation of gamma-phos]. The ESR spectra's of X-irradiated radioprotector gamma-phos have been studied. Using the analysis of relaxation effects in this sample irradiated at room temperature three paramagnetic centers have been discovered. One of these centers is classed with the free radical approximately CH2--CH--CH2 approximately (R1)-G(R1) value decreases with a decrease of irradiation temperature. Free radicals R1 are not oxidized in the air. Two other of paramagnetic centers have not been identified."} {"id": "PMID:166705", "title": "Tissue fractionation in rat brain, kidney and liver. I. Intracellular localization of a 5-methyltetrahydrofolic acid requiring enzyme.", "content": "The intracellular distribution of N-methyl-transferase requiring 5-methyl-tetrahydrofolic acid (5 MT-NMT) was studied in brain, kidney and liver of rats. Among these different tissues, the kidney displayed the highest enzyme activity, more than 20 times the activity detected in the brain. As the striatum and, to a lesser extent the hypothalamus, were found to contain slightly higher 5 MT-NMT than other cerebral regions, they were also selected for the study of the subcellular localization. Tissue fractionation was performed by differential centrifugation yielding five different fractions which were analyzed for their enzymatic content not only of 5 MT-NMT but also of marker enzymes, such as cytochrome oxidase, acid phosphatase and inosine diphosphatase. In all the tissues studied, 5 MT-NMT was recovered in the supernatant fraction. Therefore one may consider this enzyme to belong to the cytosol. Although a neuronal localization cannot be excluded, it is beyond doubt that the enzyme is contained in other cellular types. In the brain fractionation, the five fraction procedure seems to be very useful especially when the subcellular distribution of a given enzyme is compared to that obtained in other tissues like liver or kidney. Finally 5 MT-NMT may be considered a good marker enzyme for the supernatant fraction.", "contents": "Tissue fractionation in rat brain, kidney and liver. I. Intracellular localization of a 5-methyltetrahydrofolic acid requiring enzyme. The intracellular distribution of N-methyl-transferase requiring 5-methyl-tetrahydrofolic acid (5 MT-NMT) was studied in brain, kidney and liver of rats. Among these different tissues, the kidney displayed the highest enzyme activity, more than 20 times the activity detected in the brain. As the striatum and, to a lesser extent the hypothalamus, were found to contain slightly higher 5 MT-NMT than other cerebral regions, they were also selected for the study of the subcellular localization. Tissue fractionation was performed by differential centrifugation yielding five different fractions which were analyzed for their enzymatic content not only of 5 MT-NMT but also of marker enzymes, such as cytochrome oxidase, acid phosphatase and inosine diphosphatase. In all the tissues studied, 5 MT-NMT was recovered in the supernatant fraction. Therefore one may consider this enzyme to belong to the cytosol. Although a neuronal localization cannot be excluded, it is beyond doubt that the enzyme is contained in other cellular types. In the brain fractionation, the five fraction procedure seems to be very useful especially when the subcellular distribution of a given enzyme is compared to that obtained in other tissues like liver or kidney. Finally 5 MT-NMT may be considered a good marker enzyme for the supernatant fraction."} {"id": "PMID:166701", "title": "[Metabolic synapse. I. Effect of intracellular microinjection of 3'-5'-AMP].", "content": "Cyclic 3'-5'-AMP was injected into neurons of Helix pomatia (theta greater than 50 mu) by the current of 10(8) minus 10(9) A. This current was passed from one intracellular electrode to another by means of a photogenerator very well isolated from the ground. The injection of 3'-5'-AMP results in a depolarization and increase of the frequency of spontaneous activity. These changes continue for several seconds after the current is switched off. The intracellular injection of 5'-AMP or 5'-ATP and also extracellular application of 3'-5'-AMP by either the same or tenfold current does not change the spontaneous activity of these neurons.", "contents": "[Metabolic synapse. I. Effect of intracellular microinjection of 3'-5'-AMP]. Cyclic 3'-5'-AMP was injected into neurons of Helix pomatia (theta greater than 50 mu) by the current of 10(8) minus 10(9) A. This current was passed from one intracellular electrode to another by means of a photogenerator very well isolated from the ground. The injection of 3'-5'-AMP results in a depolarization and increase of the frequency of spontaneous activity. These changes continue for several seconds after the current is switched off. The intracellular injection of 5'-AMP or 5'-ATP and also extracellular application of 3'-5'-AMP by either the same or tenfold current does not change the spontaneous activity of these neurons."} {"id": "PMID:166702", "title": "[Wave regime of neuronal net activity].", "content": "The problem of activity wave propagation in homogeneous isotropic neural net is analyzed. All the neurons of the net are considered in the subthreshold region as summators of synaptic currents with finite memory. The expression for synaptic current on a single neuron in the steady-state regime of the wave activity propagation is found. The equation for the velocity of the wave propagation is derived and analyzed; possible limiting correlations are investigated. The results are compared with the analysis of Beurle.", "contents": "[Wave regime of neuronal net activity]. The problem of activity wave propagation in homogeneous isotropic neural net is analyzed. All the neurons of the net are considered in the subthreshold region as summators of synaptic currents with finite memory. The expression for synaptic current on a single neuron in the steady-state regime of the wave activity propagation is found. The equation for the velocity of the wave propagation is derived and analyzed; possible limiting correlations are investigated. The results are compared with the analysis of Beurle."} {"id": "PMID:166711", "title": "Effect of chronic marijuana administration of stages of primate sleep-wakefulness.", "content": "The effects of the repeated administration of delta-9-tetrahydrocannabinol on sleep-wakefulness patterns were studied in adult male squirrel monkeys. The percent time spent in slow wave sleep was reduced with chronic treatment and failed to return to base line levels after 30 days of recovery. The amount of time spent in Stage 1 or drowsy state increased with repeated treatment and remained elevated through recovery. Changes observed in other stages of sleep-wakefulness were sensitive to repeated treatment with marijuana but were found to return to base line levels during recovery.", "contents": "Effect of chronic marijuana administration of stages of primate sleep-wakefulness. The effects of the repeated administration of delta-9-tetrahydrocannabinol on sleep-wakefulness patterns were studied in adult male squirrel monkeys. The percent time spent in slow wave sleep was reduced with chronic treatment and failed to return to base line levels after 30 days of recovery. The amount of time spent in Stage 1 or drowsy state increased with repeated treatment and remained elevated through recovery. Changes observed in other stages of sleep-wakefulness were sensitive to repeated treatment with marijuana but were found to return to base line levels during recovery."} {"id": "PMID:166707", "title": "[Hydrolysis of the methyl esters of the N-arylsulfonyl derivatives of L-arginine by thrombin and trypsin].", "content": "Trypsin- and thrombin-catalysed hydrolysis of the Nalpha-aryl-sulfonyl-L-arginine methyl esters was studied. Michaelis constants and kcat were determined. The hydrolysis of the substrates by trypsin appears to depend on the polar nature of substitutes. The thrombin- catalysed reaction was believed to be sensitive to steric effects of the introducted groups.", "contents": "[Hydrolysis of the methyl esters of the N-arylsulfonyl derivatives of L-arginine by thrombin and trypsin]. Trypsin- and thrombin-catalysed hydrolysis of the Nalpha-aryl-sulfonyl-L-arginine methyl esters was studied. Michaelis constants and kcat were determined. The hydrolysis of the substrates by trypsin appears to depend on the polar nature of substitutes. The thrombin- catalysed reaction was believed to be sensitive to steric effects of the introducted groups."} {"id": "PMID:166708", "title": "[Conformational transitions in Na, K-dependent ATPase].", "content": "Conformational transitions in membrane preparations of Na, K-dependent ATPase were studied by means of mono-radical and bi-radical hydrophobic spine probes. A decrease in micro-viscosity of non-polar membrane regions in Na, K-ATPase preparation was observed under the formation of phosphorylated N, K-ATPase intermediate in the presence of ATP and Na+ ions. K+-catalysed dephosphorylation of the intermediate resulted in opposite changes. Bi-radical probes of a certain chemical structure turned to be the most sensitive indicators of conformational changes in membranes of Na, K-ATPase preparation. Na+-, K+- and ATP-induced conformational transitions are blocked with suabaine, a specific inhibitor of Na, K-ATPase, with Ca2+ oligomycin and p-chloromercuric benzoate (PCMB). K+-dependent transitions are more sensitive to oligomycin and PCMB as compared with those induced by ATP and Na+. Possible mechanisms of conformational transitions in Na, K-dependent ATPase are discussed.", "contents": "[Conformational transitions in Na, K-dependent ATPase]. Conformational transitions in membrane preparations of Na, K-dependent ATPase were studied by means of mono-radical and bi-radical hydrophobic spine probes. A decrease in micro-viscosity of non-polar membrane regions in Na, K-ATPase preparation was observed under the formation of phosphorylated N, K-ATPase intermediate in the presence of ATP and Na+ ions. K+-catalysed dephosphorylation of the intermediate resulted in opposite changes. Bi-radical probes of a certain chemical structure turned to be the most sensitive indicators of conformational changes in membranes of Na, K-ATPase preparation. Na+-, K+- and ATP-induced conformational transitions are blocked with suabaine, a specific inhibitor of Na, K-ATPase, with Ca2+ oligomycin and p-chloromercuric benzoate (PCMB). K+-dependent transitions are more sensitive to oligomycin and PCMB as compared with those induced by ATP and Na+. Possible mechanisms of conformational transitions in Na, K-dependent ATPase are discussed."} {"id": "PMID:166715", "title": "Energy metabolism in human erythrocytes: the role of phosphoglycerate kinase in cation transport.", "content": "Three models of disturbed erythrocyte metabolism, triose-depleted normal, phosphoglycerate kinase (PGK)-deficient, and pyruvate kinase (PK)-deficient cells, have been studied to examine further the role of PGK in erythrocyte cation transport. Sodium (Na-+) and potassium (K-+) transport were reduced only in cells fully depleted of triose. In such cells the PGK step presumably was inoperative due to total lack of substrate; 2,3-diphosphoglycerate (2,3-DPG) then became the sole substrate source for remaining steps in glycolysis. At increased intracellular Na-+ concentrations which normally stimulate transport and glycolysis, triose-depleted cells had marked impairment of cation transport and ouabain-inhibitable lactate and pyruvate production from 2,3-DPG. PGK-deficient cells and normal cells with high intracellular Na-+ concentrations had similar increases in transport and ouabain-inhibitable lactate production. PK-deficient cells with high intracellular Na-+ concentrations showed an appropriate increase in transport but less stimulation of lactate production. Transport was not related to total cellular adenosine triphosphate (ATP) concentration. These data suggested that normal coupled cation transport occurred despite diminished metabolite flow through PGK, as in PGK- or PK-deficient cells. Transport was diminished only in triose-depleted cells where metabolite flow through PGK was presumably absent. These data, therefore, support the concept that transport and glycolysis interact at the PGK step, although impairment of PGK must be profound before its effect on transport is evident.", "contents": "Energy metabolism in human erythrocytes: the role of phosphoglycerate kinase in cation transport. Three models of disturbed erythrocyte metabolism, triose-depleted normal, phosphoglycerate kinase (PGK)-deficient, and pyruvate kinase (PK)-deficient cells, have been studied to examine further the role of PGK in erythrocyte cation transport. Sodium (Na-+) and potassium (K-+) transport were reduced only in cells fully depleted of triose. In such cells the PGK step presumably was inoperative due to total lack of substrate; 2,3-diphosphoglycerate (2,3-DPG) then became the sole substrate source for remaining steps in glycolysis. At increased intracellular Na-+ concentrations which normally stimulate transport and glycolysis, triose-depleted cells had marked impairment of cation transport and ouabain-inhibitable lactate and pyruvate production from 2,3-DPG. PGK-deficient cells and normal cells with high intracellular Na-+ concentrations had similar increases in transport and ouabain-inhibitable lactate production. PK-deficient cells with high intracellular Na-+ concentrations showed an appropriate increase in transport but less stimulation of lactate production. Transport was not related to total cellular adenosine triphosphate (ATP) concentration. These data suggested that normal coupled cation transport occurred despite diminished metabolite flow through PGK, as in PGK- or PK-deficient cells. Transport was diminished only in triose-depleted cells where metabolite flow through PGK was presumably absent. These data, therefore, support the concept that transport and glycolysis interact at the PGK step, although impairment of PGK must be profound before its effect on transport is evident."} {"id": "PMID:166716", "title": "The actions of dihydroxyphenylalanine and dihydroxyphenylserine on the sleep-wakefulness cycle of the rat after peripheral decarboxylase inhibition.", "content": "1. The actions of dihydroxyphenylalanine (DOPA) and dihydroxyphenylserine (DOPS) were assessed on the sleep-wakefulness cycle of male Wistar rats. 2. In comparative studies the extracerebral decarboxylase was inhibited with serinetrihydroxybenzylhydrazide (RO 4-4602) before injection of DOPA or DOPS. 3. DOPA (80-160 mg/kg, i.p.) with or without previous inhibition of the peripheral decarboxylase gave rise to an initial significant increase of slow wave activity, which may be related to a release of 5-hydroxytryptamine. 4. During the subsequent 8 h sessions, DOPA significantly decreased slow wave sleep and rapid eye movement sleep (REM) and increased wakefulness. 5. DOPS (80-160 mg/kg, i.p.) did not significantly modify the sleep-wakefulness cycle apart from a decrease of the latency for the first REM episode after 160 mg/kg in the RO 4-4602 pretreated animals.", "contents": "The actions of dihydroxyphenylalanine and dihydroxyphenylserine on the sleep-wakefulness cycle of the rat after peripheral decarboxylase inhibition. 1. The actions of dihydroxyphenylalanine (DOPA) and dihydroxyphenylserine (DOPS) were assessed on the sleep-wakefulness cycle of male Wistar rats. 2. In comparative studies the extracerebral decarboxylase was inhibited with serinetrihydroxybenzylhydrazide (RO 4-4602) before injection of DOPA or DOPS. 3. DOPA (80-160 mg/kg, i.p.) with or without previous inhibition of the peripheral decarboxylase gave rise to an initial significant increase of slow wave activity, which may be related to a release of 5-hydroxytryptamine. 4. During the subsequent 8 h sessions, DOPA significantly decreased slow wave sleep and rapid eye movement sleep (REM) and increased wakefulness. 5. DOPS (80-160 mg/kg, i.p.) did not significantly modify the sleep-wakefulness cycle apart from a decrease of the latency for the first REM episode after 160 mg/kg in the RO 4-4602 pretreated animals."} {"id": "PMID:166717", "title": "Acetylcholine-sensitive cells in the caudal medulla of the rat: distribution, pharmacology and effects of pentobarbitone.", "content": "1. The distribution of cholinoceptive and non-cholinoceptive cells in various nuclei of the caudal medulla of the rat is described. 2. The nature of the responses of cells of the paramedian reticular nucleus and of the perihypoglossal nuclei to electrophoretically applied acetylcholine (ACh) was investigated. 3. In unanaesthetized decerebrate preparations ACh responses were usually of a \"fast onset-fast offset\" nature. Dihydro-beta-erythroidine was a more effective antagonist than atropine. 4. In rats anaesthetized with barbiturate nearly all the tach responses showed a slower onset and prolonged action. Atropine was the more effective antagonist. 5. The synaptic responses of cells of the paramedian reticular and perihypoglossal nuclei to stimulation of glossopharyngeal, superior laryngeal, lingual and hypoglossal nerves were investigated. It is concluded that ACh does not mediate the responses at the level of these nuclei.", "contents": "Acetylcholine-sensitive cells in the caudal medulla of the rat: distribution, pharmacology and effects of pentobarbitone. 1. The distribution of cholinoceptive and non-cholinoceptive cells in various nuclei of the caudal medulla of the rat is described. 2. The nature of the responses of cells of the paramedian reticular nucleus and of the perihypoglossal nuclei to electrophoretically applied acetylcholine (ACh) was investigated. 3. In unanaesthetized decerebrate preparations ACh responses were usually of a \"fast onset-fast offset\" nature. Dihydro-beta-erythroidine was a more effective antagonist than atropine. 4. In rats anaesthetized with barbiturate nearly all the tach responses showed a slower onset and prolonged action. Atropine was the more effective antagonist. 5. The synaptic responses of cells of the paramedian reticular and perihypoglossal nuclei to stimulation of glossopharyngeal, superior laryngeal, lingual and hypoglossal nerves were investigated. It is concluded that ACh does not mediate the responses at the level of these nuclei."} {"id": "PMID:166718", "title": "Modulation by acetylcholine of adrenergic transmission in the rabbit ear artery.", "content": "1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission.", "contents": "Modulation by acetylcholine of adrenergic transmission in the rabbit ear artery. 1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission."} {"id": "PMID:166719", "title": "The effects of cyclic adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate and theophylline on renin secretion in the isolated perfused kidney of the rat.", "content": "1. The influence of cyclic adenosine 3',5'-monophosphate (cyclic AMP), cylic guanosine 3',5'-monophosphate (cyclic GMP) and theophylline on renin secretion was examined in the isolated kidney of the rat perfused with Krebs dextran solution. 2. Neither cyclic AMP (10(-6) to 10(-4) M) nor dibytyryl cyclic AMP (10(-5) M) produced an increase in renin secretion. 3. Cyclic GMP and 8 Br-cyclic GMP caused a small rise in renin secretion in some experiments but this effect was independent of the dose and its physiological significance is uncertain. 4. Theophylline (10(-6) to 10(14) M) caused a significant elevation in renin secretion which was not blocked by (+)-propranolol. Theophylline with cyclic AMP or cyclic GMP did not produce an amplified effect. 5. Despite previous suggestions that cyclic AMP stimulated renin secretion, this could not be confirmed in the present preparation. Since there is no evidence that cyclic AMP or cyclic GMP (or their derivatives, dibutyryl cyclic AMP and 8 Br-cyclic GMP) enter the cells, it will be necessary to study their activity in isolated juxtaglomerular cells to define a possible role.", "contents": "The effects of cyclic adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate and theophylline on renin secretion in the isolated perfused kidney of the rat. 1. The influence of cyclic adenosine 3',5'-monophosphate (cyclic AMP), cylic guanosine 3',5'-monophosphate (cyclic GMP) and theophylline on renin secretion was examined in the isolated kidney of the rat perfused with Krebs dextran solution. 2. Neither cyclic AMP (10(-6) to 10(-4) M) nor dibytyryl cyclic AMP (10(-5) M) produced an increase in renin secretion. 3. Cyclic GMP and 8 Br-cyclic GMP caused a small rise in renin secretion in some experiments but this effect was independent of the dose and its physiological significance is uncertain. 4. Theophylline (10(-6) to 10(14) M) caused a significant elevation in renin secretion which was not blocked by (+)-propranolol. Theophylline with cyclic AMP or cyclic GMP did not produce an amplified effect. 5. Despite previous suggestions that cyclic AMP stimulated renin secretion, this could not be confirmed in the present preparation. Since there is no evidence that cyclic AMP or cyclic GMP (or their derivatives, dibutyryl cyclic AMP and 8 Br-cyclic GMP) enter the cells, it will be necessary to study their activity in isolated juxtaglomerular cells to define a possible role."} {"id": "PMID:166720", "title": "Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction.", "content": "1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited.", "contents": "Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction. 1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited."} {"id": "PMID:166724", "title": "Effect of infection with gonococci on myeloperoxidase activity of leucocytes.", "content": "Lyosomal myeloperoxidase activity in human phagocytic leucocytes was stimulated by incubation with virulent (T1) and avirulent (T4) forms of Neisseria gonorrhoeae. The amount of activity, assayed by bacterial iodination (125-iodine) after 30 min. exposure to the pagocytes in the absence of serum, was about fifty times greater in cells infected with T4 strains. In the presence of heated human serum, or its IgG component, myeloperoxidase activity increased, but T1-Stimulated activity was significantly less than that of T4 and was not proportional to multiplicity of infection. From these results and from those of a previous study we conclude that T1 can stimulate leucocyte myeloperoxidase activity from an extracellular location, that for this activity a serum fraction is required, and that this may be a mechanism responsible for some of the killing of the membrane associated T1.", "contents": "Effect of infection with gonococci on myeloperoxidase activity of leucocytes. Lyosomal myeloperoxidase activity in human phagocytic leucocytes was stimulated by incubation with virulent (T1) and avirulent (T4) forms of Neisseria gonorrhoeae. The amount of activity, assayed by bacterial iodination (125-iodine) after 30 min. exposure to the pagocytes in the absence of serum, was about fifty times greater in cells infected with T4 strains. In the presence of heated human serum, or its IgG component, myeloperoxidase activity increased, but T1-Stimulated activity was significantly less than that of T4 and was not proportional to multiplicity of infection. From these results and from those of a previous study we conclude that T1 can stimulate leucocyte myeloperoxidase activity from an extracellular location, that for this activity a serum fraction is required, and that this may be a mechanism responsible for some of the killing of the membrane associated T1."} {"id": "PMID:166726", "title": "[Hypersomnia by isthmic lesion in cat. II. Neurophysiological and pharmacological study].", "content": "(1) The bilateral destruction of the region of the dorsal norepinephrine bundle in the isthmus or in the mesencephalon induces a significant increase of both paradoxical sleep (PS) (up to 400%) and of slow-wave sleep (SWS). The increase of PS lasts for 4-5 days while the increase of SWS lasts at least 8-10 days. The same phenomenon is observed after total hypophysectomy. (2) control lesions effectuated in the isthmus outside the area of the dorsal norepinephrine bundle do not affect significantly the slee-walking cycle. (3) pretreatment with p-chlorophenylalanine suppresses the increase of sleep if the lesion is effectuated at the time of maximum insomnia, while a significant increase of PS is still observed if the lesion is made at the time of the recovery of sleep. (4) the mechanisms of this hypersomnia are discussed in light of the biochemical results showing an increase of the biosynthesis of serotonin in the rostral raphe system. It is postulated that some neurons of the dorsal norepinephrine bundle might tonically control the activity of the raphe system.", "contents": "[Hypersomnia by isthmic lesion in cat. II. Neurophysiological and pharmacological study]. (1) The bilateral destruction of the region of the dorsal norepinephrine bundle in the isthmus or in the mesencephalon induces a significant increase of both paradoxical sleep (PS) (up to 400%) and of slow-wave sleep (SWS). The increase of PS lasts for 4-5 days while the increase of SWS lasts at least 8-10 days. The same phenomenon is observed after total hypophysectomy. (2) control lesions effectuated in the isthmus outside the area of the dorsal norepinephrine bundle do not affect significantly the slee-walking cycle. (3) pretreatment with p-chlorophenylalanine suppresses the increase of sleep if the lesion is effectuated at the time of maximum insomnia, while a significant increase of PS is still observed if the lesion is made at the time of the recovery of sleep. (4) the mechanisms of this hypersomnia are discussed in light of the biochemical results showing an increase of the biosynthesis of serotonin in the rostral raphe system. It is postulated that some neurons of the dorsal norepinephrine bundle might tonically control the activity of the raphe system."} {"id": "PMID:166727", "title": "Cholinergic agents affect two receptors that modulate transmitter release at a central synapse in Aplsia californica.", "content": "A unitary, monosynaptic and presumably cholinergic EPSP recorded in cell R15 of the abdominal ganglion of Aplysia californica undergoes depression followed by facilitation when the presynaptic axon is repetitively stimulated at a rate of 1-3 pulses/sec. During trains of stimulation which produced this sequence of phenomena, the effects of a large number of agents known to affect cholinergic transmission in other systems were studied. The agents could be divided into 4 classes: (1) agents having no effect upon transmission at this cholinergic junction; (2) agents of a class typified by curare, which depressed all EPSPs of a train to the same extent, and which are believed to be acting in this system solely as competitive postsynaptic blockers; (3) agents typified by acetylcholine and carbachol (ACh class), which selectively depressed earlier EPSPs of a train more than later EPSPs and which appear to act by reducing the fractional release of transmitter; (4) agents typified by trimethidinium (trimethidinium class), which selectively depress later EPSPs of a train more than earlier EPSPs and which appear to act by reducing the rate of transmitter supply into the readily releasable pool. Neither the ACh class nor the trimethidinium class produced these selective effects on different pulses in the train by changes in the postsynaptic membrane potential or membrane resistance. Nor did they act by stimulating or inhibiting other recorded inputs onto R15. Iontophoretic application of acetylcholine onto R15 indicated that the effect of trimethidinium could not be explained by an alteration in desensitization of a postsynaptic acetylcholine receptor. The structural specificity of the presynaptic receptors mediating the action of the ACh and trimethidinium classes was demonstrated by the use of a larger number of structurally related compounds.", "contents": "Cholinergic agents affect two receptors that modulate transmitter release at a central synapse in Aplsia californica. A unitary, monosynaptic and presumably cholinergic EPSP recorded in cell R15 of the abdominal ganglion of Aplysia californica undergoes depression followed by facilitation when the presynaptic axon is repetitively stimulated at a rate of 1-3 pulses/sec. During trains of stimulation which produced this sequence of phenomena, the effects of a large number of agents known to affect cholinergic transmission in other systems were studied. The agents could be divided into 4 classes: (1) agents having no effect upon transmission at this cholinergic junction; (2) agents of a class typified by curare, which depressed all EPSPs of a train to the same extent, and which are believed to be acting in this system solely as competitive postsynaptic blockers; (3) agents typified by acetylcholine and carbachol (ACh class), which selectively depressed earlier EPSPs of a train more than later EPSPs and which appear to act by reducing the fractional release of transmitter; (4) agents typified by trimethidinium (trimethidinium class), which selectively depress later EPSPs of a train more than earlier EPSPs and which appear to act by reducing the rate of transmitter supply into the readily releasable pool. Neither the ACh class nor the trimethidinium class produced these selective effects on different pulses in the train by changes in the postsynaptic membrane potential or membrane resistance. Nor did they act by stimulating or inhibiting other recorded inputs onto R15. Iontophoretic application of acetylcholine onto R15 indicated that the effect of trimethidinium could not be explained by an alteration in desensitization of a postsynaptic acetylcholine receptor. The structural specificity of the presynaptic receptors mediating the action of the ACh and trimethidinium classes was demonstrated by the use of a larger number of structurally related compounds."} {"id": "PMID:166728", "title": "The influence of nerve growth factor, potassium depolarization and dibutyryl (cyclic) adenosine 3',5'-monophosphate on explant cultures of chick embryo sympathetic ganglia.", "content": "Optimal nerve growth factor (NGF) and potassium concentrations for the culture of explants of single chick embryo sympathetic ganglia in Leighton tubes are described. NGF increases ganglionic monoamine oxidase (MAO; E.C.1.4.3.4) activity in a dose dependent fashion with maximum effects at a concentration of about 8 U/ml NGF. Peak activity compares closely with values seen in chick ganglia in vivo. Potassium-induced depolarization (45 mM K-+) also increases MAO activity; but the extent of the increase depends upon (NGF concentration, for there is little or no increase at high NGF concentrations. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid (db cyclic AMP) can mimic the potassium-induced increase in MAO.", "contents": "The influence of nerve growth factor, potassium depolarization and dibutyryl (cyclic) adenosine 3',5'-monophosphate on explant cultures of chick embryo sympathetic ganglia. Optimal nerve growth factor (NGF) and potassium concentrations for the culture of explants of single chick embryo sympathetic ganglia in Leighton tubes are described. NGF increases ganglionic monoamine oxidase (MAO; E.C.1.4.3.4) activity in a dose dependent fashion with maximum effects at a concentration of about 8 U/ml NGF. Peak activity compares closely with values seen in chick ganglia in vivo. Potassium-induced depolarization (45 mM K-+) also increases MAO activity; but the extent of the increase depends upon (NGF concentration, for there is little or no increase at high NGF concentrations. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid (db cyclic AMP) can mimic the potassium-induced increase in MAO."} {"id": "PMID:166731", "title": "A study of inhibitory antagonism in cat visual cortex.", "content": "Since there seems to be good evidence that GABA may act as an inhibitory neurotransmitter in the mammalian cortex, we tested the effects of an antagonist of GABA, namely the alkaloid bicuculine, on the response properties of visual cortex neurons, using a computer-controlled stimulus presentation system to assess quantitatively the changes in receptive field organization after the drug. Complex cells were most affected, increasing both evoked and spontaneous activity and losing some of their specificities for stimulus parameters such as orientation and direction. Hyper-complex cells lost their inhibitory flanks, responding equally well to long and short bars after the drug. Simple cells were the least affected, usually becoming somewhat depressed after the drug. Preliminary tests with another inhibitory amino acid antagonist, strychnine, showed that it excited simple cells, indicating that possibly more than one inhibitory transmitter is at work in the cortex. The results are discussed with relation to the synaptic anatomy of the cortex, and it is concluded that a class of stellate cells, using GABA, is a likely candidate for the transmitter of some intracortical inhibition.", "contents": "A study of inhibitory antagonism in cat visual cortex. Since there seems to be good evidence that GABA may act as an inhibitory neurotransmitter in the mammalian cortex, we tested the effects of an antagonist of GABA, namely the alkaloid bicuculine, on the response properties of visual cortex neurons, using a computer-controlled stimulus presentation system to assess quantitatively the changes in receptive field organization after the drug. Complex cells were most affected, increasing both evoked and spontaneous activity and losing some of their specificities for stimulus parameters such as orientation and direction. Hyper-complex cells lost their inhibitory flanks, responding equally well to long and short bars after the drug. Simple cells were the least affected, usually becoming somewhat depressed after the drug. Preliminary tests with another inhibitory amino acid antagonist, strychnine, showed that it excited simple cells, indicating that possibly more than one inhibitory transmitter is at work in the cortex. The results are discussed with relation to the synaptic anatomy of the cortex, and it is concluded that a class of stellate cells, using GABA, is a likely candidate for the transmitter of some intracortical inhibition."} {"id": "PMID:166732", "title": "The response of the immature fowl to multiple injections of adrenocorticotrophic hormone.", "content": "1. Treating chicks, from 1 d or 5 weeks of age with ACTH three times weekly for 3 weeks depresses growth and causes adrenal hypertrophy at dose rates of 30 IU/kg or more, and depletion of adrenal cholesterol (greater than 10 IU/kg). 2. Treating chicks five times weekly at a dose rate of 30 IU/kg was as effective as a dose of 120 IU/kg three times weekly. 3. Plasma glucose and FFA concentrations of chicks treated thrice weekly with 120 IU ACTH/kg for 3 weeks were within the normal range. 4. Rhode Island Reds were more sensitive to ACTH than Light Sussex. 5. Adrenal cholesterol stores in normal chicks show significant variations with season.", "contents": "The response of the immature fowl to multiple injections of adrenocorticotrophic hormone. 1. Treating chicks, from 1 d or 5 weeks of age with ACTH three times weekly for 3 weeks depresses growth and causes adrenal hypertrophy at dose rates of 30 IU/kg or more, and depletion of adrenal cholesterol (greater than 10 IU/kg). 2. Treating chicks five times weekly at a dose rate of 30 IU/kg was as effective as a dose of 120 IU/kg three times weekly. 3. Plasma glucose and FFA concentrations of chicks treated thrice weekly with 120 IU ACTH/kg for 3 weeks were within the normal range. 4. Rhode Island Reds were more sensitive to ACTH than Light Sussex. 5. Adrenal cholesterol stores in normal chicks show significant variations with season."} {"id": "PMID:166733", "title": "The effects of various treatments on the microbial flora of whole poultry carcasses with particular reference to Staphylococcus aureus contamination.", "content": "Experiments are described in which the effects of dipping defrosted eviscerated poultry carcasses, for various periods, in acetic, lactic, succinic and citric acids, hypochlorite solution containing 200 ppm free Cl2 and in water at temperatures from 70 degrees C to 100 degrees C on the microbial flora were determined. 2. Hot (70 degrees C) water dipping for 2 min appeared to be the treatment most likely to succeed in reducing Staph. aureus, giving reductions of staphylococci of from 63 to greater than 99%, without completely eliminating other organisms. 3. A storage experiment showed this method to be relatively safe, provided the carcasses were refrigerated to less than 3 degrees C as soon as possible after treatment and held at this temperature until adequately cooked.", "contents": "The effects of various treatments on the microbial flora of whole poultry carcasses with particular reference to Staphylococcus aureus contamination. Experiments are described in which the effects of dipping defrosted eviscerated poultry carcasses, for various periods, in acetic, lactic, succinic and citric acids, hypochlorite solution containing 200 ppm free Cl2 and in water at temperatures from 70 degrees C to 100 degrees C on the microbial flora were determined. 2. Hot (70 degrees C) water dipping for 2 min appeared to be the treatment most likely to succeed in reducing Staph. aureus, giving reductions of staphylococci of from 63 to greater than 99%, without completely eliminating other organisms. 3. A storage experiment showed this method to be relatively safe, provided the carcasses were refrigerated to less than 3 degrees C as soon as possible after treatment and held at this temperature until adequately cooked."} {"id": "PMID:166734", "title": "The effects of ascorbic acid deficiency on calcium and collagen metabolism in cultured fetal rat bones.", "content": "The effects of ascorbic acid deficiency on growth and calcification of bone were studied in whole 18-day fetal rat radii and ulnae cultured in a chemically defined medium. Ascorbic acid deficiency decreased the formation of labeled hydroxyporline from labeled proline in both bone shafts and cartilage ends while incorporation of tryptophan was maintained. Dry weights and collagen content of bone and cartilage were decreased, but calcification was not affected. The optimun initial concentration of ascorbic acid for collagen synthesis was 200 mug/ml. The effect of ascorbic acid was not antagonized by glucoascorbic acid or replaced by dithiothreitol. Decreased collagen synthesis in ascorbic acid deficiency could not be ascribed to loss of available peptidyl proline hydorxylase. Formation of underhydroxylated collagen and its release into the medium accounted for much of the decrease in hydroxylated collagen in ascorbic acid deficient bones. Nevertheless, the total newly synthesized collagen, as measured by collagenase digestion, was still decreased. Similar effects were exerted by alpha, alpha'-dipyridyl which also inhibited general protein synthesis. Ascorbic acid did not stimulate proline incorporation into collagen in the presence of alpha, alpha'-dipyridyl.", "contents": "The effects of ascorbic acid deficiency on calcium and collagen metabolism in cultured fetal rat bones. The effects of ascorbic acid deficiency on growth and calcification of bone were studied in whole 18-day fetal rat radii and ulnae cultured in a chemically defined medium. Ascorbic acid deficiency decreased the formation of labeled hydroxyporline from labeled proline in both bone shafts and cartilage ends while incorporation of tryptophan was maintained. Dry weights and collagen content of bone and cartilage were decreased, but calcification was not affected. The optimun initial concentration of ascorbic acid for collagen synthesis was 200 mug/ml. The effect of ascorbic acid was not antagonized by glucoascorbic acid or replaced by dithiothreitol. Decreased collagen synthesis in ascorbic acid deficiency could not be ascribed to loss of available peptidyl proline hydorxylase. Formation of underhydroxylated collagen and its release into the medium accounted for much of the decrease in hydroxylated collagen in ascorbic acid deficient bones. Nevertheless, the total newly synthesized collagen, as measured by collagenase digestion, was still decreased. Similar effects were exerted by alpha, alpha'-dipyridyl which also inhibited general protein synthesis. Ascorbic acid did not stimulate proline incorporation into collagen in the presence of alpha, alpha'-dipyridyl."} {"id": "PMID:166735", "title": "Mitochondrial granules in human osteoblasts with a reference to one case of osteogenesis imperfecta.", "content": "Electron-dense granules in mitochondria from prenatal human osteoblasts, postnatal human osteoblasts, and from osteoblasts derived from a child with osteogenesis imperfecta congenita are described. The mitochondrial granules were of about 600 A in diameter and were attached to the mitochondrial cristae. Sections of mitochondria from prenatal osteoblasts showed an average number of 10 granuales per mitochondrial section, whereas sections of mitochondria of postnatal osteoblasts showed only occasionally 1-2 granules per mitochondrial section. Mitochondria from osteoblasts derived from the child with an untreated osteogenesis imperfecta congenita showed an average number of 10 granules per mitochondrial section.", "contents": "Mitochondrial granules in human osteoblasts with a reference to one case of osteogenesis imperfecta. Electron-dense granules in mitochondria from prenatal human osteoblasts, postnatal human osteoblasts, and from osteoblasts derived from a child with osteogenesis imperfecta congenita are described. The mitochondrial granules were of about 600 A in diameter and were attached to the mitochondrial cristae. Sections of mitochondria from prenatal osteoblasts showed an average number of 10 granuales per mitochondrial section, whereas sections of mitochondria of postnatal osteoblasts showed only occasionally 1-2 granules per mitochondrial section. Mitochondria from osteoblasts derived from the child with an untreated osteogenesis imperfecta congenita showed an average number of 10 granules per mitochondrial section."} {"id": "PMID:166736", "title": "Relationship between RNA polymerase and protein kinase activities in rat mammary gland nuclei.", "content": "1. Extracts from rat mammary gland nuclei contain cyclic AMP -independent protein kinases which phosphorylate casein rather than histone. 2. A major increase in nuclear protein kinase activity occurred during late pregnancy and was maintained with the onset of lactation. 3. Two major peaks of activity were resolved by chomatography of nuclear extracts on DEAE-Sephadex; the first (NI) appeared in the void volume and the second (NII) was eluted by 0.05-0.12 M ammonium sulfate. Several other regions of lesser activity were also present. 4. Protein kinases in the cytosol 105,000 times g supernatant, precipitated by 70 percent ammonium sulfate, dialyzed against buffer, and chromatographed on DEAE-Sephadex, yielded a major components phosphorylated histone in preference to casein, and this was stimulated by cyclic AMP if histone was the substrate, but only the first (void volume) fraction was cyclic AMP-dependent when casein was used. 5. Most of RNA polymerases Ib and II, derived from the nucleolus and nucleoplasm, respectively, appeared in column fractions distinct from those containing the major NI and NII protein kinases. 6. Cyclic AMP altered the amount of RNA product synthesized by polymerases Ib and II, but the explanation for this is unknown. Due to their elution profiles and cyclic AMP-independence, protein kinases NI and NII are excluded from playing a catalytic role in these effects; participation of quantitatively minor protein kinases which co-elute with polymerase Ib and II is not yet excluded.", "contents": "Relationship between RNA polymerase and protein kinase activities in rat mammary gland nuclei. 1. Extracts from rat mammary gland nuclei contain cyclic AMP -independent protein kinases which phosphorylate casein rather than histone. 2. A major increase in nuclear protein kinase activity occurred during late pregnancy and was maintained with the onset of lactation. 3. Two major peaks of activity were resolved by chomatography of nuclear extracts on DEAE-Sephadex; the first (NI) appeared in the void volume and the second (NII) was eluted by 0.05-0.12 M ammonium sulfate. Several other regions of lesser activity were also present. 4. Protein kinases in the cytosol 105,000 times g supernatant, precipitated by 70 percent ammonium sulfate, dialyzed against buffer, and chromatographed on DEAE-Sephadex, yielded a major components phosphorylated histone in preference to casein, and this was stimulated by cyclic AMP if histone was the substrate, but only the first (void volume) fraction was cyclic AMP-dependent when casein was used. 5. Most of RNA polymerases Ib and II, derived from the nucleolus and nucleoplasm, respectively, appeared in column fractions distinct from those containing the major NI and NII protein kinases. 6. Cyclic AMP altered the amount of RNA product synthesized by polymerases Ib and II, but the explanation for this is unknown. Due to their elution profiles and cyclic AMP-independence, protein kinases NI and NII are excluded from playing a catalytic role in these effects; participation of quantitatively minor protein kinases which co-elute with polymerase Ib and II is not yet excluded."} {"id": "PMID:166737", "title": "Effects of intraventricular injections of N-6,O-2-Dibutyryl adenosine 3,5-monophosphate on the rat brain cholinergic system.", "content": "Intraventricular injections of dibutyryl cyclic AMP effected increases of acetylcholine in the cerebral cortex-striatal and subcortical regions. No increase in choline acetyltransferase activity was observed; however, there was a significant decrease in acetylcholinesterase activity in the subcortical region.", "contents": "Effects of intraventricular injections of N-6,O-2-Dibutyryl adenosine 3,5-monophosphate on the rat brain cholinergic system. Intraventricular injections of dibutyryl cyclic AMP effected increases of acetylcholine in the cerebral cortex-striatal and subcortical regions. No increase in choline acetyltransferase activity was observed; however, there was a significant decrease in acetylcholinesterase activity in the subcortical region."} {"id": "PMID:166738", "title": "Observations on abortions in cattle: a comparison of pathological, microbiological and immunological findings in aborted foetuses and foetuses collected at abattoirs.", "content": "Fifty nonaborted and 50 aborted bovine foetuses were examined utilizing histology, immunoelectrophoresis, bacteriology and the fluorescent antibody technique. Lesions were observed in 12 of the nonaborted foesuses and in four of these immunoglobulins were demonstrated. In addition, two of the nonaborted foetuses had immunoglobulins in the absence of observed lesions. Lesions were observed in 48 of the aborted foetuses and immunoglobulins were detected in 22 of these. An etiological diagnosis was arrived at in 24 of the 50 aborted foetuses. The tissues most frequently observed to have lesions of diagnostic significance were eyelid, intestine, liver, lung and placenta. Intestinal lesions were observed in several foetuses in association with a variety of agents including infectious bovine rhinotracheitis. Foetuses diagnosed as aborting because of mycotic infection consistently displayed lesions in their eyelids. The value of taking eyelid sections in cases of suspected mycotic abortions, the significance of foetal intestinal lesions, the evaluation of abomasal aspirates and the diagnostic importance of immunoglobulin determinations in aborted foetuses are discussed.", "contents": "Observations on abortions in cattle: a comparison of pathological, microbiological and immunological findings in aborted foetuses and foetuses collected at abattoirs. Fifty nonaborted and 50 aborted bovine foetuses were examined utilizing histology, immunoelectrophoresis, bacteriology and the fluorescent antibody technique. Lesions were observed in 12 of the nonaborted foesuses and in four of these immunoglobulins were demonstrated. In addition, two of the nonaborted foetuses had immunoglobulins in the absence of observed lesions. Lesions were observed in 48 of the aborted foetuses and immunoglobulins were detected in 22 of these. An etiological diagnosis was arrived at in 24 of the 50 aborted foetuses. The tissues most frequently observed to have lesions of diagnostic significance were eyelid, intestine, liver, lung and placenta. Intestinal lesions were observed in several foetuses in association with a variety of agents including infectious bovine rhinotracheitis. Foetuses diagnosed as aborting because of mycotic infection consistently displayed lesions in their eyelids. The value of taking eyelid sections in cases of suspected mycotic abortions, the significance of foetal intestinal lesions, the evaluation of abomasal aspirates and the diagnostic importance of immunoglobulin determinations in aborted foetuses are discussed."} {"id": "PMID:166739", "title": "Electron microscopic findings of cells with inclusion bodies in experimental hemorrhagic enteritis of turkeys.", "content": "The spleen, liver, bone marrow and intestines of two turkeys in which hemorrhagic enteritis of turkeys was experimentally reproduced were examined electron-microscopically. Intranuclear inclusion bodies as described in a previous report were found in all the tissues examined. These occupied most of the area in affected nuclei and were composed of viral particles with morphological characteristics of an adenovirus. The cells with the inclusions were divided into two types of cells, immature and reticular cells. There was some variety in the stage of differentiation of the former cells. As the viral particles developed the cells degenerated and disintegrated. A few particles had been released into the cytoplasm of the degenerated cells but no particles were present in intercellular spaces.", "contents": "Electron microscopic findings of cells with inclusion bodies in experimental hemorrhagic enteritis of turkeys. The spleen, liver, bone marrow and intestines of two turkeys in which hemorrhagic enteritis of turkeys was experimentally reproduced were examined electron-microscopically. Intranuclear inclusion bodies as described in a previous report were found in all the tissues examined. These occupied most of the area in affected nuclei and were composed of viral particles with morphological characteristics of an adenovirus. The cells with the inclusions were divided into two types of cells, immature and reticular cells. There was some variety in the stage of differentiation of the former cells. As the viral particles developed the cells degenerated and disintegrated. A few particles had been released into the cytoplasm of the degenerated cells but no particles were present in intercellular spaces."} {"id": "PMID:166740", "title": "Effect of pasteurization and evaporation on foot-and-mouth disease virus in whole milk from infected cows.", "content": "The effects of pasteurization and evaporation on foot-and-mouth disease virus in whole milk from infected cows obtained one day postinoculation were studied. Virus survived the heating of milk at high temperature-short time pasteurization at 75 degrees C for 15-17 seconds. In addition, virus from infected milk survived heating at 80 degrees C for the same time. Infective virus also survived in the pasteurized milk after evaporation at 65 degrees C to 50% of the original volume. The bovine udder was found to be highly susceptible to foot-and-mouth disease virus replication. Seven log10 plaque-forming units/ml of virus were recovered in whole milk 24 hours postinoculation, and decreasing titers were recovered for as long as seven days postinoculation.", "contents": "Effect of pasteurization and evaporation on foot-and-mouth disease virus in whole milk from infected cows. The effects of pasteurization and evaporation on foot-and-mouth disease virus in whole milk from infected cows obtained one day postinoculation were studied. Virus survived the heating of milk at high temperature-short time pasteurization at 75 degrees C for 15-17 seconds. In addition, virus from infected milk survived heating at 80 degrees C for the same time. Infective virus also survived in the pasteurized milk after evaporation at 65 degrees C to 50% of the original volume. The bovine udder was found to be highly susceptible to foot-and-mouth disease virus replication. Seven log10 plaque-forming units/ml of virus were recovered in whole milk 24 hours postinoculation, and decreasing titers were recovered for as long as seven days postinoculation."} {"id": "PMID:166741", "title": "Isolation of equine herpesvirus type 1 from a horse with an acute paralytic disease.", "content": "A Standardbred mare became paralyzed shortly after showing signs of an upper respiratory infection. The mare was euthanized and equine herpesvirus type 1 was isolated from the brain and spinal cord.", "contents": "Isolation of equine herpesvirus type 1 from a horse with an acute paralytic disease. A Standardbred mare became paralyzed shortly after showing signs of an upper respiratory infection. The mare was euthanized and equine herpesvirus type 1 was isolated from the brain and spinal cord."} {"id": "PMID:166742", "title": "Unique immunobiological aspects of head and neck squamous carcinoma.", "content": "The immune reactivity of patients with squamous carcinoma of the head and neck region was compared with that of patients with squamous carcinoma of the female pelvic organs and patients with adenocarcinomas, melanomas, and sarcomas. The reactivity of patients with clinically localized tumors was compared with that of cured patients and a large normal population. Patients with squamous carcinomas of the head and neck region and female pelvic organs displayed higher incidences of impaired cellular immune competence than patients with malignancies of other histologic types. Among cured patients, those previously treated for squamous carcinoma were unique in that they displayed cellular immune defects and serum suppressants of in vitro immune reactivity similar to tumor-bearing patients. Antibodies to herpes simplex virus nonvirion antigen was found in high incidence only among patients with squamous carcinomas, and the incidences in tumor-bearing and cured patients were similar. The persisting immune defects in cured squamous carcinoma patients give importance to the determination of the role of genetic and environmental factors in the induction of these tumors. The associations made between herpes virus and squamous carcinoma offer an explanation for the defects and also an approach for the definition of the factors involved in squamous carcinogenesis. The findings are clinically relevant to the isolation of population groups at high risk for the development of squamous carcinoma, as a rational basis for the development of prophylactic measures, and as a basis for more effective therapeutic regimens.", "contents": "Unique immunobiological aspects of head and neck squamous carcinoma. The immune reactivity of patients with squamous carcinoma of the head and neck region was compared with that of patients with squamous carcinoma of the female pelvic organs and patients with adenocarcinomas, melanomas, and sarcomas. The reactivity of patients with clinically localized tumors was compared with that of cured patients and a large normal population. Patients with squamous carcinomas of the head and neck region and female pelvic organs displayed higher incidences of impaired cellular immune competence than patients with malignancies of other histologic types. Among cured patients, those previously treated for squamous carcinoma were unique in that they displayed cellular immune defects and serum suppressants of in vitro immune reactivity similar to tumor-bearing patients. Antibodies to herpes simplex virus nonvirion antigen was found in high incidence only among patients with squamous carcinomas, and the incidences in tumor-bearing and cured patients were similar. The persisting immune defects in cured squamous carcinoma patients give importance to the determination of the role of genetic and environmental factors in the induction of these tumors. The associations made between herpes virus and squamous carcinoma offer an explanation for the defects and also an approach for the definition of the factors involved in squamous carcinogenesis. The findings are clinically relevant to the isolation of population groups at high risk for the development of squamous carcinoma, as a rational basis for the development of prophylactic measures, and as a basis for more effective therapeutic regimens."} {"id": "PMID:166743", "title": "Adenocarcinoma of the larynx.", "content": "Adenocarcinomas make up less than one per cent of laryngeal malignancies. Nonspecific adenocarcinomas and adenoid cystic carcinomas comprise most of the glandular neoplasms. Adenoid cystic carcinoma has a slight preponderance in females, and often follows a long course similar to this tumor when it occurs in salivary glands. The nonspecific adenocarcinomas occur predominately in males and have a low survival with most patients dying within two years. Less common adenocarcinomas include oncocytoid carcinoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma.", "contents": "Adenocarcinoma of the larynx. Adenocarcinomas make up less than one per cent of laryngeal malignancies. Nonspecific adenocarcinomas and adenoid cystic carcinomas comprise most of the glandular neoplasms. Adenoid cystic carcinoma has a slight preponderance in females, and often follows a long course similar to this tumor when it occurs in salivary glands. The nonspecific adenocarcinomas occur predominately in males and have a low survival with most patients dying within two years. Less common adenocarcinomas include oncocytoid carcinoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma."} {"id": "PMID:166745", "title": "Adenocarcinoma of the larynx.", "content": "Nine patients with primary adenocarcinoma of the larynx representing 0.1 per cent of 888 patients with primary laryngeal malignancy treated between 1955 and 1971 are reported. Following surgical therapy, four patients are alive without disease and five patients are dead due to their disease. Survival time was not related to histopathologic type, stage of disease, or mode of therapy. We cautiously advocate the use of the most conservative surgery feasible as the primary treatment of this poorly understood and highly fatal disease.", "contents": "Adenocarcinoma of the larynx. Nine patients with primary adenocarcinoma of the larynx representing 0.1 per cent of 888 patients with primary laryngeal malignancy treated between 1955 and 1971 are reported. Following surgical therapy, four patients are alive without disease and five patients are dead due to their disease. Survival time was not related to histopathologic type, stage of disease, or mode of therapy. We cautiously advocate the use of the most conservative surgery feasible as the primary treatment of this poorly understood and highly fatal disease."} {"id": "PMID:166748", "title": "Comparative pharmacological studies on butriptyline and some related standard tricyclic antidepressants.", "content": "Butriptyline was compared with imipramine and other tricyclic antidepressants for its ability to modify: (a) contractions of the cat nictitating membrane induced by noradrenaline (NA) and 5-hydroxytryptamine (5-HT), (b) the adrenergic neuron blocking action of guanethidine in the guinea pig vas deferns, (c) the rabbit's electroencephalogram (EEG) and physostigmine arousal, and (d) the sleep pattern of the rat. Imipramine and amitriptyline potentiated the NA and 5-HT effects on the nictitating membrane and antagonized the inhibitory actions of guanethidine in the guinea pig vas deferens, whereas iprindole and butriptyline were ineffective. These results are consistent with the ability of these drugs to block the neuronal uptake of catecholamines. Butriptyline was a potent blocker of the arousal reaction induced by physostigmine. Butriptyline (20--30 mg/kg) and amitriptyline (10--20 mg/kg) reduced rapid eye movement sleep with a conmitant increase in non-rapid eye movement sleep. This may be a reflection of the dual activity observed in the clinic with these compounds, namely, antidepressant and antianxiety effects.", "contents": "Comparative pharmacological studies on butriptyline and some related standard tricyclic antidepressants. Butriptyline was compared with imipramine and other tricyclic antidepressants for its ability to modify: (a) contractions of the cat nictitating membrane induced by noradrenaline (NA) and 5-hydroxytryptamine (5-HT), (b) the adrenergic neuron blocking action of guanethidine in the guinea pig vas deferns, (c) the rabbit's electroencephalogram (EEG) and physostigmine arousal, and (d) the sleep pattern of the rat. Imipramine and amitriptyline potentiated the NA and 5-HT effects on the nictitating membrane and antagonized the inhibitory actions of guanethidine in the guinea pig vas deferens, whereas iprindole and butriptyline were ineffective. These results are consistent with the ability of these drugs to block the neuronal uptake of catecholamines. Butriptyline was a potent blocker of the arousal reaction induced by physostigmine. Butriptyline (20--30 mg/kg) and amitriptyline (10--20 mg/kg) reduced rapid eye movement sleep with a conmitant increase in non-rapid eye movement sleep. This may be a reflection of the dual activity observed in the clinic with these compounds, namely, antidepressant and antianxiety effects."} {"id": "PMID:166749", "title": "Response of hepatic carbohydrate and cyclic AMP metabolism to cadmium treatment in rats.", "content": "Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) for 21 or 45 days into rats significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase, and glucose-6-phosphatase, increased the concentrations of glucose and urea in the blood, and decreased the levels of glycogen in the liver. Whereas chronic cadmium treatment failed to alter adenosine-3',5'-monophosphate phosphodiesterase (phosphodiesterase) activity, the endogenous levels of cyclic AMP (cAMP) and the activity of basal- and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased in cadmium-injected animals. Treatment with the higher dose (1.0 mg/kg) of cadmium chloride for 45 days produced greater metabolic alterations in hepatic tissue than those seen with the lower dose (0.25 mg/kg) given for a shorter period of time (21 days). Discontinuation of cadmium administration for 14 days in rats previously injected with cadmium chloride (1 mg/kg per day) for 21 days, failed to reverse the observed changes in hepatic cAMP or carbohydrate metabolism. A similar persistence of metabolic alterations was noted in rats treated with cadmium (1 mg/kg per day) for 45 days and subsequently maintained without additional treatment for 28 days. Administration of an acute dose of cadmium chloride (60 mg/kg) decreased hepatic phosphodiesterase activity and glycogen content 1 h after the injection. In addition, acute cadmium exposure increased blood glucose, serum urea, and hepatic cAMP levels, and produced an augmentation of basal- and fluoride-activated AC. However, the activities of various hepatic gluconeogenic enzymes remained unaffected in animals given an acute dose of cadmium chloride (60 mg/kg). Data provide evidence that suggests that the gluconeogenic potential of liver is markedly enhanced following chronic exposure to cadmium and that the cadmium-induced changes in carbohydrate metabolism may be associated with an enhanced synthesis of cAMP. In addition, the present study shows that the cadmium-induced metabolic alterations persist even after the cessation of cadmium treatment for a period of 28 days.", "contents": "Response of hepatic carbohydrate and cyclic AMP metabolism to cadmium treatment in rats. Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) for 21 or 45 days into rats significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase, and glucose-6-phosphatase, increased the concentrations of glucose and urea in the blood, and decreased the levels of glycogen in the liver. Whereas chronic cadmium treatment failed to alter adenosine-3',5'-monophosphate phosphodiesterase (phosphodiesterase) activity, the endogenous levels of cyclic AMP (cAMP) and the activity of basal- and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased in cadmium-injected animals. Treatment with the higher dose (1.0 mg/kg) of cadmium chloride for 45 days produced greater metabolic alterations in hepatic tissue than those seen with the lower dose (0.25 mg/kg) given for a shorter period of time (21 days). Discontinuation of cadmium administration for 14 days in rats previously injected with cadmium chloride (1 mg/kg per day) for 21 days, failed to reverse the observed changes in hepatic cAMP or carbohydrate metabolism. A similar persistence of metabolic alterations was noted in rats treated with cadmium (1 mg/kg per day) for 45 days and subsequently maintained without additional treatment for 28 days. Administration of an acute dose of cadmium chloride (60 mg/kg) decreased hepatic phosphodiesterase activity and glycogen content 1 h after the injection. In addition, acute cadmium exposure increased blood glucose, serum urea, and hepatic cAMP levels, and produced an augmentation of basal- and fluoride-activated AC. However, the activities of various hepatic gluconeogenic enzymes remained unaffected in animals given an acute dose of cadmium chloride (60 mg/kg). Data provide evidence that suggests that the gluconeogenic potential of liver is markedly enhanced following chronic exposure to cadmium and that the cadmium-induced changes in carbohydrate metabolism may be associated with an enhanced synthesis of cAMP. In addition, the present study shows that the cadmium-induced metabolic alterations persist even after the cessation of cadmium treatment for a period of 28 days."} {"id": "PMID:166750", "title": "Further observations on the response of the glomerular filtration rate to glucagon: comparison with secretin.", "content": "Glucagon causes marked elevations of glomerular filtration rate (GFR) in dogs when administered intravenously (i.v.) in small doses. The associated natriuresis is thought to be entirely due to increments in the filtered sodium load. In this study, renal denervation, thyroparathyroidectomy, and blockade of cholinergic, alpha- and beta-adrenergic, dopaminergic and histaminergic receptors did not prevent the usual glucagon-induced elevations of GFR or rate of sodium excretion (UNaV). This effect of glucagon was not mediated through the release of cyclic AMP, or by plasma compositional changes of Ca-2+, K+, or amino acids. Pure porcine secretin, in doses of 5--10 mug/min delivered either i.v. or into the left renal artery did not alter GFR; clearance of the p-aminohippurate (CPAH) or UNaV in either hydropenic or saline-loaded dogs. Nor did this polypeptide, structurally very similar to glucagon, abolish the effect of glucagon on GFR. It did, however, partially inhibit the glucagon-induced natriuresis, presumably by preventing a previously undetected glucagon action on tubular reabsorption of sodium.", "contents": "Further observations on the response of the glomerular filtration rate to glucagon: comparison with secretin. Glucagon causes marked elevations of glomerular filtration rate (GFR) in dogs when administered intravenously (i.v.) in small doses. The associated natriuresis is thought to be entirely due to increments in the filtered sodium load. In this study, renal denervation, thyroparathyroidectomy, and blockade of cholinergic, alpha- and beta-adrenergic, dopaminergic and histaminergic receptors did not prevent the usual glucagon-induced elevations of GFR or rate of sodium excretion (UNaV). This effect of glucagon was not mediated through the release of cyclic AMP, or by plasma compositional changes of Ca-2+, K+, or amino acids. Pure porcine secretin, in doses of 5--10 mug/min delivered either i.v. or into the left renal artery did not alter GFR; clearance of the p-aminohippurate (CPAH) or UNaV in either hydropenic or saline-loaded dogs. Nor did this polypeptide, structurally very similar to glucagon, abolish the effect of glucagon on GFR. It did, however, partially inhibit the glucagon-induced natriuresis, presumably by preventing a previously undetected glucagon action on tubular reabsorption of sodium."} {"id": "PMID:166751", "title": "Conjunctival papillomas in norther Canadian natives.", "content": "Cases of conjunctival papilloma evaluated at a hospital that acts as a referral centre for native people (Indian and Inuit) from northern Alberta and the Northwest Territories were compared with those from other hospitals in the same region whose referral base is primarily non-native. When the data were standardized for population unitsof 100,000 the tumours appeared to be occurring with a greater frequency among lnuit of the Western Arctic. These findings are supported statistically, although it is possible that bias may have been introduced by the small number of cases and other related factors.", "contents": "Conjunctival papillomas in norther Canadian natives. Cases of conjunctival papilloma evaluated at a hospital that acts as a referral centre for native people (Indian and Inuit) from northern Alberta and the Northwest Territories were compared with those from other hospitals in the same region whose referral base is primarily non-native. When the data were standardized for population unitsof 100,000 the tumours appeared to be occurring with a greater frequency among lnuit of the Western Arctic. These findings are supported statistically, although it is possible that bias may have been introduced by the small number of cases and other related factors."} {"id": "PMID:166754", "title": "Structural studies of the capsular polysaccharide of Klebsiella type 81.", "content": "The structure of the capsular polysaccharide from Klebsiella Type 81 has beeninvestigated. Methlylation analysis, uronic acid degradation, Smith degradation, andgraded acid hydrolysis were the principle methods used. Theanomeric nature of theglycosidic linkages was determined by characterization of fragments obtained from thevarious methods of degradation used. One of the L-rhamnosidic linkages was notpresent in any of these fragments, but is assumed to be an alpha-linkage from consideerationsof optical-rotation data. These studies show that they polysaccharide consits of thefollowing hexasaccharide repeating-unit: yield2)-alpha-L-Rhap-(1yields3)-alpha-L-Rhap-(1-yields4)-beta-D-GlcAP-(1-yields2)-alpha-L-Rhap-(1-yields3)-alpha-L-Rhap-(1-yields3)-beta-D-Galp-(1-yields.", "contents": "Structural studies of the capsular polysaccharide of Klebsiella type 81. The structure of the capsular polysaccharide from Klebsiella Type 81 has beeninvestigated. Methlylation analysis, uronic acid degradation, Smith degradation, andgraded acid hydrolysis were the principle methods used. Theanomeric nature of theglycosidic linkages was determined by characterization of fragments obtained from thevarious methods of degradation used. One of the L-rhamnosidic linkages was notpresent in any of these fragments, but is assumed to be an alpha-linkage from consideerationsof optical-rotation data. These studies show that they polysaccharide consits of thefollowing hexasaccharide repeating-unit: yield2)-alpha-L-Rhap-(1yields3)-alpha-L-Rhap-(1-yields4)-beta-D-GlcAP-(1-yields2)-alpha-L-Rhap-(1-yields3)-alpha-L-Rhap-(1-yields3)-beta-D-Galp-(1-yields."} {"id": "PMID:166755", "title": "Structural studies of the capsular polysaccharide of Klebsiella type 59.", "content": "The structure of the capsular polysaccharide from Klebsiella type 59 has been investigated by methylation analysis, a modified Smith-degradation procedure, and uronic acid degradation followed by oxidation and elimination of the substituents of the oxidized residue. The oligomeric fragments produced by these degradative procedures were isolated and characterized. O-Acetyl groups were identified and their position determined. The polysaccharide consists of the following pentasaccharide repeating-unit (dotted lines indicate that only some of the residues carry the O-acetyl substituent). See article.", "contents": "Structural studies of the capsular polysaccharide of Klebsiella type 59. The structure of the capsular polysaccharide from Klebsiella type 59 has been investigated by methylation analysis, a modified Smith-degradation procedure, and uronic acid degradation followed by oxidation and elimination of the substituents of the oxidized residue. The oligomeric fragments produced by these degradative procedures were isolated and characterized. O-Acetyl groups were identified and their position determined. The polysaccharide consists of the following pentasaccharide repeating-unit (dotted lines indicate that only some of the residues carry the O-acetyl substituent). See article."} {"id": "PMID:166756", "title": "Structural studies of the capsular polysaccharide of Klebsiella type 28.", "content": "The capsular polysaccharide from Klebsiella type 28 has been studied by methylation analysis, a modified Smith-degradation procedure, and uronic acid degradation with subsequent oxidation and elimination of the substituents of the oxidized residue. The polysaccharide contained the hexasaccharide repeating-unit shown below. The terminal D-glucopyranose residue was hydrolysed by emulsin, indicating a beta linkage. The anomeric natures of other glycosidic linkages were determined by characterization of fragments obtained during the degradative studies. The D-galactopyranose residue was not present in any fragment, but is assumed to be alpha-linked from optical-rotation considerations. (see article)", "contents": "Structural studies of the capsular polysaccharide of Klebsiella type 28. The capsular polysaccharide from Klebsiella type 28 has been studied by methylation analysis, a modified Smith-degradation procedure, and uronic acid degradation with subsequent oxidation and elimination of the substituents of the oxidized residue. The polysaccharide contained the hexasaccharide repeating-unit shown below. The terminal D-glucopyranose residue was hydrolysed by emulsin, indicating a beta linkage. The anomeric natures of other glycosidic linkages were determined by characterization of fragments obtained during the degradative studies. The D-galactopyranose residue was not present in any fragment, but is assumed to be alpha-linked from optical-rotation considerations. (see article)"} {"id": "PMID:166757", "title": "Acyloxy neighboring-group participation in the acid-catalyzed cleavage of methyl 2,3-anhydro-beta-D-ribofuranoside.", "content": "The reaction of methyl 2,3-anhydro-beta-D-ribofuranoside with hydrogen bromide in an acetic acid-acetic anhydride solution leads to the formation of methyl 2,3-di-O-acetyl-5-bromo-5-deoxy-alpha,beta-D-xylofuranoside. Similar treatment of methyl 2,3-anhydro-5-O-benzoyl-beta-D-robofuranoside provided methyl 2-O-acetyl-3-O-benzoyl-5-bromo-5-deoxy-alpha,beta-D-xylofuranosides. The position of halogen substitution was ascertained by hydrogenolysis to the resultant 5-deoxy sugars, which were characterized by their n.m.r. spectra. Confirmation of the structural assignment for methyl 2-O-acetyl-3-O-benzoyl-5-deoxy-alpha,beta-D-xylofuranoside was obtained by synthesis from 1,2-O-isopropylidene-alpha-D-xylofuranose. The formation of the 5-bromo derivatives under the reported conditions probably occurred through the intermediacy of the 3,5-acyloxonium ions. Similar conversions were observed when the starting compound was treated with hydrogen chloride, acetyl bromide, or acetyl chloride in acetic acid-acetic anhydride solutions.", "contents": "Acyloxy neighboring-group participation in the acid-catalyzed cleavage of methyl 2,3-anhydro-beta-D-ribofuranoside. The reaction of methyl 2,3-anhydro-beta-D-ribofuranoside with hydrogen bromide in an acetic acid-acetic anhydride solution leads to the formation of methyl 2,3-di-O-acetyl-5-bromo-5-deoxy-alpha,beta-D-xylofuranoside. Similar treatment of methyl 2,3-anhydro-5-O-benzoyl-beta-D-robofuranoside provided methyl 2-O-acetyl-3-O-benzoyl-5-bromo-5-deoxy-alpha,beta-D-xylofuranosides. The position of halogen substitution was ascertained by hydrogenolysis to the resultant 5-deoxy sugars, which were characterized by their n.m.r. spectra. Confirmation of the structural assignment for methyl 2-O-acetyl-3-O-benzoyl-5-deoxy-alpha,beta-D-xylofuranoside was obtained by synthesis from 1,2-O-isopropylidene-alpha-D-xylofuranose. The formation of the 5-bromo derivatives under the reported conditions probably occurred through the intermediacy of the 3,5-acyloxonium ions. Similar conversions were observed when the starting compound was treated with hydrogen chloride, acetyl bromide, or acetyl chloride in acetic acid-acetic anhydride solutions."} {"id": "PMID:166760", "title": "In vitro polyoma DNA synthesis: self-annealing properties of short DNA chains.", "content": "Short DNA chains, isolated from in vitro pulse-labeled replicating polyoma DNA, exhibit some degree of self-complementarity (28% resistance to S1 nuclease after self-annealing to plateau levels). This level of self-annealing is not increased if short DNA chains present as free single-stranded DNA after extraction are included in the hybridization, excluding a selective loss of chains from one side of the growing fork and supporting a semi-discontinuous mode of chain growth. This mode also applies to restricted synthesis conditions under which a relative excess of short chains is made, since no increase in the self-annealing of such short chains is observed. The self-annealing that can be measured is higher for the faster sedimenting portion (46%) of the short DNA chains than for the slower sedimenting portion (18.5%), indicating that it is most likely due to contaminating continuously growing strands from the other side of the fork. High self-annealing values (up to 60%) are obtained if virus stocks generating defective DNA are used for infection. Restriction endonuclease (Hpall) characterization of such DNA shows evidence for the presence of multiple origins of replication. One of several possible mechanisms is discussed by which replicating defective DNA can generate self-complementary short chains despite a semi-discontinuous mode of replication.", "contents": "In vitro polyoma DNA synthesis: self-annealing properties of short DNA chains. Short DNA chains, isolated from in vitro pulse-labeled replicating polyoma DNA, exhibit some degree of self-complementarity (28% resistance to S1 nuclease after self-annealing to plateau levels). This level of self-annealing is not increased if short DNA chains present as free single-stranded DNA after extraction are included in the hybridization, excluding a selective loss of chains from one side of the growing fork and supporting a semi-discontinuous mode of chain growth. This mode also applies to restricted synthesis conditions under which a relative excess of short chains is made, since no increase in the self-annealing of such short chains is observed. The self-annealing that can be measured is higher for the faster sedimenting portion (46%) of the short DNA chains than for the slower sedimenting portion (18.5%), indicating that it is most likely due to contaminating continuously growing strands from the other side of the fork. High self-annealing values (up to 60%) are obtained if virus stocks generating defective DNA are used for infection. Restriction endonuclease (Hpall) characterization of such DNA shows evidence for the presence of multiple origins of replication. One of several possible mechanisms is discussed by which replicating defective DNA can generate self-complementary short chains despite a semi-discontinuous mode of replication."} {"id": "PMID:166761", "title": "Effect of a single treatment with the alkylating carcinogens dimethynitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. I. Test for induction of liver carcinomas.", "content": "A single injection of dimethylnitrosamine (DMN), 12.0-15.6 mg-kg, given to 100 g female rats 24 h after partial hepatectomy, induced hepatocellular carcinoma. No animals receiving DMN without partial hepatectomy developed liver carcinomas. Previous evidence had suggested that the incidence of tumours was highest when DMN was administered during the wave of DNA replication which follows partial hepatectomy. The present experiments made this suggestive evidence statistically significant. A single treatment with diethylnitrosamine (DEN) induced liver cell cancer when given to intact or to partially hepatectomised rats. No tumors developed when another alkylating carcinogen, methyl methanesulphonate (MMS), was administered after partial hepatectomy. The significance of these results in relation to the mechanism of initiation of carcinogenesis is discussed.", "contents": "Effect of a single treatment with the alkylating carcinogens dimethynitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. I. Test for induction of liver carcinomas. A single injection of dimethylnitrosamine (DMN), 12.0-15.6 mg-kg, given to 100 g female rats 24 h after partial hepatectomy, induced hepatocellular carcinoma. No animals receiving DMN without partial hepatectomy developed liver carcinomas. Previous evidence had suggested that the incidence of tumours was highest when DMN was administered during the wave of DNA replication which follows partial hepatectomy. The present experiments made this suggestive evidence statistically significant. A single treatment with diethylnitrosamine (DEN) induced liver cell cancer when given to intact or to partially hepatectomised rats. No tumors developed when another alkylating carcinogen, methyl methanesulphonate (MMS), was administered after partial hepatectomy. The significance of these results in relation to the mechanism of initiation of carcinogenesis is discussed."} {"id": "PMID:166762", "title": "Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. II. Alkylation of DNA and inhibition of DNA replication.", "content": "Experiments were carried out to determine whether replication of alkylated DNA could be involved in the initiation of hepatocellular carcinoma which results from a single administration of dimethylnitrosamine (DMN) given after partial hepatectomy. The incidence of tumours is higher when DMN is given during the wave of DNA synthesis induced by the operation than when given in the early prereplicative stage. Therefore the alkylation of DNA in the regenerating liver by DMN given at these times and the effect of DMN on DNA synthesis were investigated. The extent, duration and pattern of alkylation of DNA, including the formation of 0-6-methylguanine, were similar whether DMN was given in the early pre-replicative stage (6 h after the operation) or during the period of DNA synthesis (at 24 h). DMN given a 6 h very greatly reduced the wave of DNA replication which would otherwise have ensued. When given at 24 h, by which time DNA synthesis was already taking place, DMN reduced the rate of incorporation of (-3H)thymidine after 1-2 h delay. However, in neither case was DNA synthesis reduced to the level occurring in normal intact liver. Treatment with diethylnitrosamine (DEN) at 6 h or at 24 h had a similar effect to DMN on the wave of DNA replication induced by partial hepatectomy. Methyl methanesulphonate (MMS given in the early pre-replicative stage delayed the wave of DNA synthesis by about 8 h, but when it did take place the extent of synthesis was as great as in untreated animals. When given during the period of DNA replication, MMS rapidly reduced the rate of synthesis. As in the case of the nitrosamines, synthesis was not reduced to the level occuring in normal intact animals. The difference from the nitrosamines lies in the nature of the alkylated bases formed in DNA. The fact that a single treatment with DMN induces cancer in partially hepatectomised animals but not in intact adult animals is not considered to be due to a gross difference in the nature of the alkylation of DNA. The experiments described support the concept that replication of DNA containing bases which are likely to mispair during replication may be necessary to 'fix' the lesion and thus cause a permanent inheritable change in the genetic material.", "contents": "Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. II. Alkylation of DNA and inhibition of DNA replication. Experiments were carried out to determine whether replication of alkylated DNA could be involved in the initiation of hepatocellular carcinoma which results from a single administration of dimethylnitrosamine (DMN) given after partial hepatectomy. The incidence of tumours is higher when DMN is given during the wave of DNA synthesis induced by the operation than when given in the early prereplicative stage. Therefore the alkylation of DNA in the regenerating liver by DMN given at these times and the effect of DMN on DNA synthesis were investigated. The extent, duration and pattern of alkylation of DNA, including the formation of 0-6-methylguanine, were similar whether DMN was given in the early pre-replicative stage (6 h after the operation) or during the period of DNA synthesis (at 24 h). DMN given a 6 h very greatly reduced the wave of DNA replication which would otherwise have ensued. When given at 24 h, by which time DNA synthesis was already taking place, DMN reduced the rate of incorporation of (-3H)thymidine after 1-2 h delay. However, in neither case was DNA synthesis reduced to the level occurring in normal intact liver. Treatment with diethylnitrosamine (DEN) at 6 h or at 24 h had a similar effect to DMN on the wave of DNA replication induced by partial hepatectomy. Methyl methanesulphonate (MMS given in the early pre-replicative stage delayed the wave of DNA synthesis by about 8 h, but when it did take place the extent of synthesis was as great as in untreated animals. When given during the period of DNA replication, MMS rapidly reduced the rate of synthesis. As in the case of the nitrosamines, synthesis was not reduced to the level occuring in normal intact animals. The difference from the nitrosamines lies in the nature of the alkylated bases formed in DNA. The fact that a single treatment with DMN induces cancer in partially hepatectomised animals but not in intact adult animals is not considered to be due to a gross difference in the nature of the alkylation of DNA. The experiments described support the concept that replication of DNA containing bases which are likely to mispair during replication may be necessary to 'fix' the lesion and thus cause a permanent inheritable change in the genetic material."} {"id": "PMID:166763", "title": "Effect of adenosine 3',5'-cyclic monophosphate on the RNA and DNA synthesis and cell proliferation of rat hepatocytes in primary culture: a radioautographic study.", "content": "The effect of a 24-h treatment with various doses (from 1.5-10-minus 8 to 3.0-10-minus 3 M) of adenosine 3',5'-cyclic monophospahte (cAMP) on morphometric parameters, [5--3H]uridine radioactivity concentration (URC), [methyl--3H]thymidine [Me--3H]-Tr) labelling index per hour (L.I./h) and per cent mitotic index (M.I.%) of young rat differentiated hepatocytes in primary tissue culture were investigated by morphometric and radioautographic methods. In such cells cAMP was found to induce: (1) a reduction of the apparent surface area (ASA) of total nucleoli, karyoplasm and cytoplasm; (2) significant increases in URC of all the subcellular compartments at all the dosages employed (only cAMP at 1.5-10-minus 8 M did not change karyoplasmic and cytoplasmic URC values); (3) marked increments in [Me--3H]Tdr L.I./h and M.I.% from the lowest dose up to 1.5-10-minus 4 M; at higher doses the L.I./h and M.I.% were less stimulated or approached control values. In cultured rat hepatocytes, adenosine-5'-phosphate (5'-AMP) (1.5-10-minus 4 M per 24 h) increased the karyoplasmic and total cell ASA, the lone total nucleolar URC and both the L.I./h and M.I.%. However, these metabolic effects were significantly less intense than those elicited by isomolar cAMP. Theophylline (Theo) (5.5-10-minus 5 M per 24 h) reduced the in vitro rat hepatocyte total nucleolar ASA but affected neither other morphometric nor any of the URC values. The same dose of Theo plus cAMP (1.5-10-minus M) had no morphometric effect but significantly increased the URC values of all primary rat hepatocyte compartments. Actinomycin D (DAct) (0.1 mug/ml per 24 h) plus cAMP (1.5-10-minus 4 M) decreased the cultured rat hepatocyte total nucleolar ASA but enlarged that of karyoplasm and cytoplasm and, further, markedly curtailed all the compartmental URC values. These data support the hypothesis that cAMP amplified the template activity of the liver chromatin and accelerates the flow of differentiated primary young rat hepatocytes into the various stages of the mitotic cell cycle.", "contents": "Effect of adenosine 3',5'-cyclic monophosphate on the RNA and DNA synthesis and cell proliferation of rat hepatocytes in primary culture: a radioautographic study. The effect of a 24-h treatment with various doses (from 1.5-10-minus 8 to 3.0-10-minus 3 M) of adenosine 3',5'-cyclic monophospahte (cAMP) on morphometric parameters, [5--3H]uridine radioactivity concentration (URC), [methyl--3H]thymidine [Me--3H]-Tr) labelling index per hour (L.I./h) and per cent mitotic index (M.I.%) of young rat differentiated hepatocytes in primary tissue culture were investigated by morphometric and radioautographic methods. In such cells cAMP was found to induce: (1) a reduction of the apparent surface area (ASA) of total nucleoli, karyoplasm and cytoplasm; (2) significant increases in URC of all the subcellular compartments at all the dosages employed (only cAMP at 1.5-10-minus 8 M did not change karyoplasmic and cytoplasmic URC values); (3) marked increments in [Me--3H]Tdr L.I./h and M.I.% from the lowest dose up to 1.5-10-minus 4 M; at higher doses the L.I./h and M.I.% were less stimulated or approached control values. In cultured rat hepatocytes, adenosine-5'-phosphate (5'-AMP) (1.5-10-minus 4 M per 24 h) increased the karyoplasmic and total cell ASA, the lone total nucleolar URC and both the L.I./h and M.I.%. However, these metabolic effects were significantly less intense than those elicited by isomolar cAMP. Theophylline (Theo) (5.5-10-minus 5 M per 24 h) reduced the in vitro rat hepatocyte total nucleolar ASA but affected neither other morphometric nor any of the URC values. The same dose of Theo plus cAMP (1.5-10-minus M) had no morphometric effect but significantly increased the URC values of all primary rat hepatocyte compartments. Actinomycin D (DAct) (0.1 mug/ml per 24 h) plus cAMP (1.5-10-minus 4 M) decreased the cultured rat hepatocyte total nucleolar ASA but enlarged that of karyoplasm and cytoplasm and, further, markedly curtailed all the compartmental URC values. These data support the hypothesis that cAMP amplified the template activity of the liver chromatin and accelerates the flow of differentiated primary young rat hepatocytes into the various stages of the mitotic cell cycle."} {"id": "PMID:166767", "title": "[Different action of alpha-methyl-DOPA on sleep and labyrinth learning in 2 inbred strains of mice].", "content": "In two inbred mice strains C 57 BR and C 57 BL/6 presenting the same type of sleep, but a different capacity of learning, Alpha-Methyl-Dopa (100 mg/kg) injected after every session, suppresses paradoxical sleep completely for 9 to 11 h. Maze-learning performance is retarded in C 57 BR mice, but facilitated in C 57 BL/6.", "contents": "[Different action of alpha-methyl-DOPA on sleep and labyrinth learning in 2 inbred strains of mice]. In two inbred mice strains C 57 BR and C 57 BL/6 presenting the same type of sleep, but a different capacity of learning, Alpha-Methyl-Dopa (100 mg/kg) injected after every session, suppresses paradoxical sleep completely for 9 to 11 h. Maze-learning performance is retarded in C 57 BR mice, but facilitated in C 57 BL/6."} {"id": "PMID:166768", "title": "Acute subendocardial myocardial infarction in patients. Its detection by Technetium 99-m stannous pyrophosphate myocardial scintigrams.", "content": "Eighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannour pyrophosphate (99m-Tc-PYP). Seventeen of these patients had ECG and enzymatic evidence suggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were postivie demonstrating increased 99m-Tc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence of acute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus 99m-Tc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial infarction in patients. The absolute frequency with shich subendocardial myocardial infarction can be recognized utilizing this technique will have to be established in a larger number of patients in the future.", "contents": "Acute subendocardial myocardial infarction in patients. Its detection by Technetium 99-m stannous pyrophosphate myocardial scintigrams. Eighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannour pyrophosphate (99m-Tc-PYP). Seventeen of these patients had ECG and enzymatic evidence suggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were postivie demonstrating increased 99m-Tc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence of acute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus 99m-Tc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial infarction in patients. The absolute frequency with shich subendocardial myocardial infarction can be recognized utilizing this technique will have to be established in a larger number of patients in the future."} {"id": "PMID:166769", "title": "Possible identity between the hepatoma alkaline phosphatase and an isozyme of human amniotic membrane (FL cells).", "content": "The electrophoretically faster migrating alkaline phosphatase isozyme in FL cells derived from the human amniotic membrane was similar in some of the enzymatic and immunochemical properties to the variant alkaline phosphatase which occurs in serum and cancerous tissue of some patients with hepatocellular carcinoma. These facts suggest that the hepatoma-associated alkaline phosphatase may be the resurgence of the isozyme originally present in the amniotic membrane.", "contents": "Possible identity between the hepatoma alkaline phosphatase and an isozyme of human amniotic membrane (FL cells). The electrophoretically faster migrating alkaline phosphatase isozyme in FL cells derived from the human amniotic membrane was similar in some of the enzymatic and immunochemical properties to the variant alkaline phosphatase which occurs in serum and cancerous tissue of some patients with hepatocellular carcinoma. These facts suggest that the hepatoma-associated alkaline phosphatase may be the resurgence of the isozyme originally present in the amniotic membrane."} {"id": "PMID:166770", "title": "Serum lipid and lipoprotein profile in school children from a rural community.", "content": "In 447 school children 5--16 years old, in one community, serum lipid and lipoprotein levels were estimated, including total cholesterol, triglycerides, beta- and pre-beta-lipoprotein cholesterol, alpha-lipoprotein cholesterol, and the serum concentrations of beta-, pre-beta-, and alpha-lipoproteins. Mean serum cholesterol of the entire group was 188 mg/100 ml, and alpha-lipoprotein cholesterol constituted 68 mg/100 ml of this total. The levels of serum triglycerides (48.9 mg/100 ml) and pre-beta-lipoprotein (39.8 mg/100 ml) are low in children in comparison to adults. Except for pre-beta-lipoprotein levels, there was very little correlation between age and all lipids and lipoproteins in this age span. Slight differences in values were noted at certain age intervals, but there were no significant differences in values between sexes. These observations emphasize the need for evaluating lipid abnormalities in individual children by quantitating specific serum lipoproteins.", "contents": "Serum lipid and lipoprotein profile in school children from a rural community. In 447 school children 5--16 years old, in one community, serum lipid and lipoprotein levels were estimated, including total cholesterol, triglycerides, beta- and pre-beta-lipoprotein cholesterol, alpha-lipoprotein cholesterol, and the serum concentrations of beta-, pre-beta-, and alpha-lipoproteins. Mean serum cholesterol of the entire group was 188 mg/100 ml, and alpha-lipoprotein cholesterol constituted 68 mg/100 ml of this total. The levels of serum triglycerides (48.9 mg/100 ml) and pre-beta-lipoprotein (39.8 mg/100 ml) are low in children in comparison to adults. Except for pre-beta-lipoprotein levels, there was very little correlation between age and all lipids and lipoproteins in this age span. Slight differences in values were noted at certain age intervals, but there were no significant differences in values between sexes. These observations emphasize the need for evaluating lipid abnormalities in individual children by quantitating specific serum lipoproteins."} {"id": "PMID:166776", "title": "Delayed adolescence.", "content": "Delayed adolescence has several causes. Most frequent is the physiological or constitutional (hereditary) delay of growth and adolescence. This is a normal variation of growth and development, with growth, bone age and puberty retarded in a harmonious way. It carries a good prognosis with late but normal puberty and late catch-up growth leading to normal adult height. It manifests itself long before puberty by short stature and retarded bone age. True endocrine defects with permanent hypogonadism (hypothalamic-pituitary deficiency of the gonadotropinds and primary gonadal failure) are rare. Differential diagnosis before puberty is not always possible on clinical grounds alone. The most useful laboratory test consists of the LH-RH test. The i.v. injection of the recently introduced hypothalamic LH-releasing hormone, LH-RH, is followed by an age-dependent increase of the plasma gonadotropinds LH and FSH. This test allows differentiation, before puberty, between constitutional delay of growth and adolescence with a normal response for bone age, true hypothalamic-pituitary insufficiency with no response, and primary gonadal failure with an increased response. True hypogonadism requires permanent sex hormone replacement therapy. Constitutional delay of growth and adolescence in boys may present a psychosocial indication for temporary hormone therapy with testosterone.", "contents": "Delayed adolescence. Delayed adolescence has several causes. Most frequent is the physiological or constitutional (hereditary) delay of growth and adolescence. This is a normal variation of growth and development, with growth, bone age and puberty retarded in a harmonious way. It carries a good prognosis with late but normal puberty and late catch-up growth leading to normal adult height. It manifests itself long before puberty by short stature and retarded bone age. True endocrine defects with permanent hypogonadism (hypothalamic-pituitary deficiency of the gonadotropinds and primary gonadal failure) are rare. Differential diagnosis before puberty is not always possible on clinical grounds alone. The most useful laboratory test consists of the LH-RH test. The i.v. injection of the recently introduced hypothalamic LH-releasing hormone, LH-RH, is followed by an age-dependent increase of the plasma gonadotropinds LH and FSH. This test allows differentiation, before puberty, between constitutional delay of growth and adolescence with a normal response for bone age, true hypothalamic-pituitary insufficiency with no response, and primary gonadal failure with an increased response. True hypogonadism requires permanent sex hormone replacement therapy. Constitutional delay of growth and adolescence in boys may present a psychosocial indication for temporary hormone therapy with testosterone."} {"id": "PMID:166784", "title": "Metastatic malignancy of the hand.", "content": "Metastatic malignancies of the hand are infrequent and seldom initially diagnosed and often taken for infections. They usually occur at the late stage of metastatic generalization and indicate an ominous prognosis and justify surgical amputation. A case of metastasis to the distal phalanx of the left ring finger of a woman who had undergone radical mastectomy for breast cystosarcoma phylloides is reported. The evolution of this lesion, initially taken for a whitlow, lasted 45 days and eventually was treated by amputation. A review of literature confirms the rarity of the lesion, and reveals the pathological, clinical and radiographic characteristics.", "contents": "Metastatic malignancy of the hand. Metastatic malignancies of the hand are infrequent and seldom initially diagnosed and often taken for infections. They usually occur at the late stage of metastatic generalization and indicate an ominous prognosis and justify surgical amputation. A case of metastasis to the distal phalanx of the left ring finger of a woman who had undergone radical mastectomy for breast cystosarcoma phylloides is reported. The evolution of this lesion, initially taken for a whitlow, lasted 45 days and eventually was treated by amputation. A review of literature confirms the rarity of the lesion, and reveals the pathological, clinical and radiographic characteristics."} {"id": "PMID:166785", "title": "Pyrophosphate and diphosphonates in skeletal metabolism. Physiological, clinical and therapeutic aspects.", "content": "Pyrophosphate and diphosphonates produce striking results on calcium metabolism in experimental animals and man. Compounds containing P-O-P- bonds (e.g. inorganic pyrophosphate [PP-ii1 or P-C-P bonds (diphosponates) inhibit both the formation and dissolution of calcium phosphate crystals in vitro. PP-i may have a physiological function in regulating calcification and bone turnover, and obnormalities in its metabolism may occur in some human diseases notably hypophosphatasia and pseudogout. Diphosphonates inhibit ectopic calcification, and slow down resorption and bone turnover in several experimental systems in vivo. They have helped in studies of various aspects of the regulation of calcium metabolism. The diphosphonate, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) has been shown in clinical studies to be effective against ectopic calcification particularly in myositis ossificans progressiva and in disorders of increased bone resorption such as Paget's diseases and some types of osteoporosis. -99mTechnetium complexes of EHDP, PP-i and other polyphosphates have also recently been used successfully as bone scanning agents.", "contents": "Pyrophosphate and diphosphonates in skeletal metabolism. Physiological, clinical and therapeutic aspects. Pyrophosphate and diphosphonates produce striking results on calcium metabolism in experimental animals and man. Compounds containing P-O-P- bonds (e.g. inorganic pyrophosphate [PP-ii1 or P-C-P bonds (diphosponates) inhibit both the formation and dissolution of calcium phosphate crystals in vitro. PP-i may have a physiological function in regulating calcification and bone turnover, and obnormalities in its metabolism may occur in some human diseases notably hypophosphatasia and pseudogout. Diphosphonates inhibit ectopic calcification, and slow down resorption and bone turnover in several experimental systems in vivo. They have helped in studies of various aspects of the regulation of calcium metabolism. The diphosphonate, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) has been shown in clinical studies to be effective against ectopic calcification particularly in myositis ossificans progressiva and in disorders of increased bone resorption such as Paget's diseases and some types of osteoporosis. -99mTechnetium complexes of EHDP, PP-i and other polyphosphates have also recently been used successfully as bone scanning agents."} {"id": "PMID:166794", "title": "Leoprosy- clinical aspectos of nerve involvement.", "content": "Leprosy is the cause of the commonest peripheral neuropathy. The predilection of Mycobacterium leprae for nerve tissue accounts for the clinical features that are most dreaded and most characteristic of the disease. Were it not for the progressive destruction of peripheral nerve trunks and the consequences of this, leprosy would largely remain a cutaneous condition of cosmetically unsightly hypopigmented or erythematous areas and aggregations of nodular thickenings. The neurologic damage in leprosy is confined to postganglionic changes. The central nervous system is protected, although rarely in experimental situations organisms have been reported in cerebral tissues.", "contents": "Leoprosy- clinical aspectos of nerve involvement. Leprosy is the cause of the commonest peripheral neuropathy. The predilection of Mycobacterium leprae for nerve tissue accounts for the clinical features that are most dreaded and most characteristic of the disease. Were it not for the progressive destruction of peripheral nerve trunks and the consequences of this, leprosy would largely remain a cutaneous condition of cosmetically unsightly hypopigmented or erythematous areas and aggregations of nodular thickenings. The neurologic damage in leprosy is confined to postganglionic changes. The central nervous system is protected, although rarely in experimental situations organisms have been reported in cerebral tissues."} {"id": "PMID:166795", "title": "Leprosy--histopathologic aspects of nerve involvement.", "content": "The most striking single feature of the clinical manifestations of leprosy is the very wide range of appearances shown by the skin lesions. These include the vague, hypopigmented macules of indeterminate leprosy; the large, sharply defined hypopigmented anaesthetic lesions of tuberculoid leprosy; the nodules and diffuse infiltration of lepromatous leprosy; and a wide range of plaques and annular lesions of the intermediate (borderline or dimorphous) types of disease. From superficial appearances it would be impossible to say that these were manifestations of the same infection. Moreover, histologically there is a similar wide range of appearances, including minimal lymphocyte infiltration around the neurovascular bundles in indeterminate leprosy; epithelioid granulomata with Langhans' giant cells and virtually no bacilli to be seen in tuberculoid cases; and in lepromatous leprosy, histiocytic infiltration occupying the whole thickness of the dermis, with massive parasitisation by Mycobacterium leprae, of which there may be up to 10-9 per gram of tissue. Strain differences have been recognised, but appear not to be responsible for this remarkable range of manifestations; they are caused by variations in the soil, not in the seed. Leprosy is almost unique among infectious diseases in the importance that host factors play in its development. The different clinical appearances shown by different types of leprosy can be graded into a continuous series, forming a spectrum from the single or scanty lesions of tuberculoid leprosy to the total body involvement o lepromatous; and the patient with leprosy can indeed truly be said to wear his skin lesions like medals displaying his capacity to resist Myco. leprate. The histopathologic features of the developed disease have a similar spectrum, from an epithelioid granuloma to infiltration with histiocytes that are full of bacilli and are ultimately converted to foam cells (Virchow cells)...", "contents": "Leprosy--histopathologic aspects of nerve involvement. The most striking single feature of the clinical manifestations of leprosy is the very wide range of appearances shown by the skin lesions. These include the vague, hypopigmented macules of indeterminate leprosy; the large, sharply defined hypopigmented anaesthetic lesions of tuberculoid leprosy; the nodules and diffuse infiltration of lepromatous leprosy; and a wide range of plaques and annular lesions of the intermediate (borderline or dimorphous) types of disease. From superficial appearances it would be impossible to say that these were manifestations of the same infection. Moreover, histologically there is a similar wide range of appearances, including minimal lymphocyte infiltration around the neurovascular bundles in indeterminate leprosy; epithelioid granulomata with Langhans' giant cells and virtually no bacilli to be seen in tuberculoid cases; and in lepromatous leprosy, histiocytic infiltration occupying the whole thickness of the dermis, with massive parasitisation by Mycobacterium leprae, of which there may be up to 10-9 per gram of tissue. Strain differences have been recognised, but appear not to be responsible for this remarkable range of manifestations; they are caused by variations in the soil, not in the seed. Leprosy is almost unique among infectious diseases in the importance that host factors play in its development. The different clinical appearances shown by different types of leprosy can be graded into a continuous series, forming a spectrum from the single or scanty lesions of tuberculoid leprosy to the total body involvement o lepromatous; and the patient with leprosy can indeed truly be said to wear his skin lesions like medals displaying his capacity to resist Myco. leprate. The histopathologic features of the developed disease have a similar spectrum, from an epithelioid granuloma to infiltration with histiocytes that are full of bacilli and are ultimately converted to foam cells (Virchow cells)..."} {"id": "PMID:166796", "title": "Upper respiratory infection of lactating sows with transmissible gastroenteritis virus following contact exposure to infected piglets.", "content": "Ten breeding sows were left in direct contact with their newborn piglets that had been experimentally infected with transmissible gastroenteritis (TGE) virus. All sows became infected with the virus. The sows developed fever and showed mild clinical signs of the disease for a few days. The sows excreted virus in the nasal secretion, feces, and milk during the acute febrile phase of illness. Virus was isolated from the nasal secretion of one sow as early as 20 hours after contact exposure to the infected piglets. At necropsy, the virus was more frequently isolated from the tissues of the upper respiratory tract than from small intestines; this finding indicated that the TGE coronavirus replicated in the upper respiratory tract and induced an acute respiratory infection in susceptible adult swine. Neutralizing antibody was present in the sera 8 sows after 12 to 36 days during the convalescent period. From these results, we conclude that susceptible sows in direct contact with ill piglets can become infected and by excreting virus can serve as a source of TGE virus for other susceptible pigs on the premises.", "contents": "Upper respiratory infection of lactating sows with transmissible gastroenteritis virus following contact exposure to infected piglets. Ten breeding sows were left in direct contact with their newborn piglets that had been experimentally infected with transmissible gastroenteritis (TGE) virus. All sows became infected with the virus. The sows developed fever and showed mild clinical signs of the disease for a few days. The sows excreted virus in the nasal secretion, feces, and milk during the acute febrile phase of illness. Virus was isolated from the nasal secretion of one sow as early as 20 hours after contact exposure to the infected piglets. At necropsy, the virus was more frequently isolated from the tissues of the upper respiratory tract than from small intestines; this finding indicated that the TGE coronavirus replicated in the upper respiratory tract and induced an acute respiratory infection in susceptible adult swine. Neutralizing antibody was present in the sera 8 sows after 12 to 36 days during the convalescent period. From these results, we conclude that susceptible sows in direct contact with ill piglets can become infected and by excreting virus can serve as a source of TGE virus for other susceptible pigs on the premises."} {"id": "PMID:166797", "title": "Adenoviral pneumonia in a foal.", "content": "A three-week-old Arabian filly was admitted to the Large Animal Hospital with a respiratory disorder and died despite symptomatic treatment. The necropsy lesions were suggestive of viral pneumonia. An equine adenovirus were isolated from nasal and pharyngeal swabs and from several tissues after death. Typical adenovirus virions were demonstrated by electron microscopy.", "contents": "Adenoviral pneumonia in a foal. A three-week-old Arabian filly was admitted to the Large Animal Hospital with a respiratory disorder and died despite symptomatic treatment. The necropsy lesions were suggestive of viral pneumonia. An equine adenovirus were isolated from nasal and pharyngeal swabs and from several tissues after death. Typical adenovirus virions were demonstrated by electron microscopy."} {"id": "PMID:166798", "title": "Red cell enzymes.", "content": "As compared to other cells of the body, the mammalian red cell has one of the simplest structural organizations. As a result, this cell has been extensively used in studies involving the structure, function, and integrity of cell membranes as well as cytoplasmic events. Additionally, the metabolic activities of the red blood cell are also relatively simple. During the past quarter century or so, an ocean of knowledge has been gathered on various aspects of red cell metabolism and function. The fields of enzymes, hemoglobin, membrane, and metabolic products comprise the major portion of this knowledge. These advances have made valuable contributions to biochemistry and medicine. Despite these favorable aspects of this simple, anucleated cell, it must be conceded that our knowledge about the red cell is far from complete. We are still in the dark concerning the mechanism involved in several aspects of its membrane, hemoglobin, enzymes, and a large number of other constituents. For example, a large number of enzymes with known catalytic activity but with unknown function have eluded investigators despite active pursuit. This review will be a consolidation of our present knowledge of human red cell enzymes, with particular reference to their usefulness in the diagnosis and therapy of disease. Owing to the multitude of publications by prominent investigators on each of the approximately 50 enzymes discussed in this review, it was impossible to cite a majority of them.", "contents": "Red cell enzymes. As compared to other cells of the body, the mammalian red cell has one of the simplest structural organizations. As a result, this cell has been extensively used in studies involving the structure, function, and integrity of cell membranes as well as cytoplasmic events. Additionally, the metabolic activities of the red blood cell are also relatively simple. During the past quarter century or so, an ocean of knowledge has been gathered on various aspects of red cell metabolism and function. The fields of enzymes, hemoglobin, membrane, and metabolic products comprise the major portion of this knowledge. These advances have made valuable contributions to biochemistry and medicine. Despite these favorable aspects of this simple, anucleated cell, it must be conceded that our knowledge about the red cell is far from complete. We are still in the dark concerning the mechanism involved in several aspects of its membrane, hemoglobin, enzymes, and a large number of other constituents. For example, a large number of enzymes with known catalytic activity but with unknown function have eluded investigators despite active pursuit. This review will be a consolidation of our present knowledge of human red cell enzymes, with particular reference to their usefulness in the diagnosis and therapy of disease. Owing to the multitude of publications by prominent investigators on each of the approximately 50 enzymes discussed in this review, it was impossible to cite a majority of them."} {"id": "PMID:166800", "title": "Contraceptive steroid binding to the human uterine progesterone-receptor.", "content": "Using an equilibrium dialysis method, the competition was investigated between tritated-progesterone and a range of synthetic steroids for binding to 20,000 g. supernatants of human uterine endometrium and myometrium. Both types of uterine tissue showed similar patterns of progestogen binding and probably contain similar, or even identical, progesterone receptors. The gonane progestogen norgestrel binds strongly to the uterine receptors, but only the d-isomer is active. All three pregnane progestogens used in this study (chlormadinone acetate, medroxprogesterone acetate, megestrol acetate) also showed significant binding to receptors, but for the estrane progestogens, norethisterone was the only compound to show a high binding capacity. Other estranes (ethynodiol diacetate, lynestrenol, norethisterone acetate, norethynodrel) showed insignificant binding to the receptors and probably require prior metabolic activation to norethisterone before they can induce progestogenic effects.", "contents": "Contraceptive steroid binding to the human uterine progesterone-receptor. Using an equilibrium dialysis method, the competition was investigated between tritated-progesterone and a range of synthetic steroids for binding to 20,000 g. supernatants of human uterine endometrium and myometrium. Both types of uterine tissue showed similar patterns of progestogen binding and probably contain similar, or even identical, progesterone receptors. The gonane progestogen norgestrel binds strongly to the uterine receptors, but only the d-isomer is active. All three pregnane progestogens used in this study (chlormadinone acetate, medroxprogesterone acetate, megestrol acetate) also showed significant binding to receptors, but for the estrane progestogens, norethisterone was the only compound to show a high binding capacity. Other estranes (ethynodiol diacetate, lynestrenol, norethisterone acetate, norethynodrel) showed insignificant binding to the receptors and probably require prior metabolic activation to norethisterone before they can induce progestogenic effects."} {"id": "PMID:166802", "title": "Examples of adolescent group homes in alliance with larger institutions.", "content": "Use of the group home in combination with the services of larger institutions for disturbed adolescents has many treatment advantages if the home program is tailored to the specific needs of the youngsters served.", "contents": "Examples of adolescent group homes in alliance with larger institutions. Use of the group home in combination with the services of larger institutions for disturbed adolescents has many treatment advantages if the home program is tailored to the specific needs of the youngsters served."} {"id": "PMID:166803", "title": "Perianal Paget's disease: report of two cases.", "content": "A patient with extensive perianal extra-mammary Paget's disease was treated by wide local excision of the perianal skin. No underlying associated adenocarcinoma was identified, and the patient is clinically free of disease five years after treatment. A second patient had a small focus of Paget's disease confined to a hemorrhoid. The necessity for histologic evaluation of all anal lesions is emphasized.", "contents": "Perianal Paget's disease: report of two cases. A patient with extensive perianal extra-mammary Paget's disease was treated by wide local excision of the perianal skin. No underlying associated adenocarcinoma was identified, and the patient is clinically free of disease five years after treatment. A second patient had a small focus of Paget's disease confined to a hemorrhoid. The necessity for histologic evaluation of all anal lesions is emphasized."} {"id": "PMID:166804", "title": "A pharmacological model of the pathophysioloyg of schizophrenia.", "content": "A pharmacological model of the pathophysiology of schizophrenia based upon receptor site theory has been presented. This model proposes that, like any neuronal function, schizophrenia is triggered by the action of a small molecule at a specific receptor site. This interaction elicits the abnormal behavior. The model permits analysis of all existing theories of the pathogenesis of schizophrenia and furthermore makes it possible to view the pathophysiologic implications of these theories. It also mkaes it possible to understand the mechanism of action of neuroleptic agents used in the treatment of schizophrenia, regardless of which theories of pathogenesis are valid.", "contents": "A pharmacological model of the pathophysioloyg of schizophrenia. A pharmacological model of the pathophysiology of schizophrenia based upon receptor site theory has been presented. This model proposes that, like any neuronal function, schizophrenia is triggered by the action of a small molecule at a specific receptor site. This interaction elicits the abnormal behavior. The model permits analysis of all existing theories of the pathogenesis of schizophrenia and furthermore makes it possible to view the pathophysiologic implications of these theories. It also mkaes it possible to understand the mechanism of action of neuroleptic agents used in the treatment of schizophrenia, regardless of which theories of pathogenesis are valid."} {"id": "PMID:166809", "title": "[Nerve lesions following total hip replacement and other hip-joint operations].", "content": "Nerve lesions occurred in 17 patients who had undergone hip-joint operations (especially total replacement). The femoral nerve was most commonly affected, followed by sciatic and gluteal nerves, with combined pareses in six. As differential diagnosis from pseudoparesis is not always possible, electromyography should be performed in all cases. Stretching and/or squeezing are the most important causes. The operation results are significantly impaired by such nerve lesions. However, long-term results are usually satisfactory in the majority of cases. Early diagnosis and treatment are important in ensuring good therapeutic results.", "contents": "[Nerve lesions following total hip replacement and other hip-joint operations]. Nerve lesions occurred in 17 patients who had undergone hip-joint operations (especially total replacement). The femoral nerve was most commonly affected, followed by sciatic and gluteal nerves, with combined pareses in six. As differential diagnosis from pseudoparesis is not always possible, electromyography should be performed in all cases. Stretching and/or squeezing are the most important causes. The operation results are significantly impaired by such nerve lesions. However, long-term results are usually satisfactory in the majority of cases. Early diagnosis and treatment are important in ensuring good therapeutic results."} {"id": "PMID:166818", "title": "A method for determination of the specific activity of receptor-bound human chorionic gonadotropin (hCG).", "content": "Precise knowledge of the specific activity (S.A., muc/mug) of the receptor bound radiolabelled hormone is required for study of the stoichiometry of peptide hormone-receptor interactios. A radioligand receptor assay using 131-I-hCG as tracer and transplantable mouse luteoma homogenates (Biol. Reprod. 8:550, 1973) as a source of receptor was used as a model to determine the specific activity of receptor bound 125-I-hCG. Progressive saturation of the gonadotropin receptor by 125-I-hCG suggests the presence of a high affinity-low capacity binding event (saturating between 14 and 37 ng/100 mg homogenate) that does not distinguish between non-radioactive hCG and 125-I-hCG, and a low affinity-high capacity binding event (saturating between 240 and 270 ng/100 mg homogenate) that shows a preference for non-radioactive hCG over 125-I-hCG. Parallelism between bound 125-I-hCG and non-radioactive hCG in terms of competition with tracer 131-I-hCG could only be demonstrated for the high affinity event.", "contents": "A method for determination of the specific activity of receptor-bound human chorionic gonadotropin (hCG). Precise knowledge of the specific activity (S.A., muc/mug) of the receptor bound radiolabelled hormone is required for study of the stoichiometry of peptide hormone-receptor interactios. A radioligand receptor assay using 131-I-hCG as tracer and transplantable mouse luteoma homogenates (Biol. Reprod. 8:550, 1973) as a source of receptor was used as a model to determine the specific activity of receptor bound 125-I-hCG. Progressive saturation of the gonadotropin receptor by 125-I-hCG suggests the presence of a high affinity-low capacity binding event (saturating between 14 and 37 ng/100 mg homogenate) that does not distinguish between non-radioactive hCG and 125-I-hCG, and a low affinity-high capacity binding event (saturating between 240 and 270 ng/100 mg homogenate) that shows a preference for non-radioactive hCG over 125-I-hCG. Parallelism between bound 125-I-hCG and non-radioactive hCG in terms of competition with tracer 131-I-hCG could only be demonstrated for the high affinity event."} {"id": "PMID:166819", "title": "Assay of lactogenic hormones using receptors isolated from rabbit liver.", "content": "Using 125-I-labelled ovine prolactin and receptors isolated from the livers of rabbits, a sensitive method has been developed suitable for the assay of ovine, bovine, porcine, human and rat prolactins. These hormones showed competitive displacement of 125-I-ovine prolactin which was in general agreement with their respective activities in the pigeon crop sac bioassay. Human and monkey growth hormones and human placental lactogen, which have marked prolactin-like actions on mammary tissue were also effective competitors. Non-primate growth hormones (ovine, bovine, equine and canine) which do not have prolactin-like activity gave little if any displacement as did human FSH, LH, TSH, ACTH and bovine insulin. Preparations of equine and canine prolactin of varying purity gave dose-response curves although their activity as competitors relative to ovine prolactin was poor and not related to their pigeon crop stimulating activity. This indicates species differences between prolactins in hormone-receptor interaction. Experiments with antiserum to human growth hormone have suggested an effective method of making the assay specific in species such as man in which prolactin is not the sole hormone with lactogenic activity.", "contents": "Assay of lactogenic hormones using receptors isolated from rabbit liver. Using 125-I-labelled ovine prolactin and receptors isolated from the livers of rabbits, a sensitive method has been developed suitable for the assay of ovine, bovine, porcine, human and rat prolactins. These hormones showed competitive displacement of 125-I-ovine prolactin which was in general agreement with their respective activities in the pigeon crop sac bioassay. Human and monkey growth hormones and human placental lactogen, which have marked prolactin-like actions on mammary tissue were also effective competitors. Non-primate growth hormones (ovine, bovine, equine and canine) which do not have prolactin-like activity gave little if any displacement as did human FSH, LH, TSH, ACTH and bovine insulin. Preparations of equine and canine prolactin of varying purity gave dose-response curves although their activity as competitors relative to ovine prolactin was poor and not related to their pigeon crop stimulating activity. This indicates species differences between prolactins in hormone-receptor interaction. Experiments with antiserum to human growth hormone have suggested an effective method of making the assay specific in species such as man in which prolactin is not the sole hormone with lactogenic activity."} {"id": "PMID:166820", "title": "The effect of LH on cyclic AMP and progesterone in rat ovaries in vivo.", "content": "LH injected into the abdominal vein of immature female rats increased ovarian cyclec AMP levels within 1 min, and the effect lasted at least 2 hr. In PMS stimulated rats, a maximal effect on cyclic AMP levels was obtained with 5 mug of LH 10 min after injection. Significant effects were obtained with as little as 0.1 mug. The minimum effective dose required to increase ovary cyclic AMP levels in proestrus rats was 0.05 mug of LH. While 0.01 mug did not affect cyclic AMP levels, an increase in ovary progesterone was found. In other experiments, the response of cyclis AMP to LH in vivo was greater in immature ovaries than in those from animals pretreated with PMS and hCG. Small increases in cyclic AMP levels were also seen with FSH in PMS and PMS + hCG treated animals and with prostaglandin E2 and prolactin in PMS treated rats. These results parallel, to some extent, previous results found in vitro, and show that very small doses of LH can stimulate ovary cyclic AMP increases in vivo.", "contents": "The effect of LH on cyclic AMP and progesterone in rat ovaries in vivo. LH injected into the abdominal vein of immature female rats increased ovarian cyclec AMP levels within 1 min, and the effect lasted at least 2 hr. In PMS stimulated rats, a maximal effect on cyclic AMP levels was obtained with 5 mug of LH 10 min after injection. Significant effects were obtained with as little as 0.1 mug. The minimum effective dose required to increase ovary cyclic AMP levels in proestrus rats was 0.05 mug of LH. While 0.01 mug did not affect cyclic AMP levels, an increase in ovary progesterone was found. In other experiments, the response of cyclis AMP to LH in vivo was greater in immature ovaries than in those from animals pretreated with PMS and hCG. Small increases in cyclic AMP levels were also seen with FSH in PMS and PMS + hCG treated animals and with prostaglandin E2 and prolactin in PMS treated rats. These results parallel, to some extent, previous results found in vitro, and show that very small doses of LH can stimulate ovary cyclic AMP increases in vivo."} {"id": "PMID:166821", "title": "Antiestrogen action in the uterus: biological ineffectiveness of nuclear bound estradiol after antiestrogen.", "content": "These studies attempt to analyze the basis of the estrogenic and antiestrogenic action of three nonsteroidal clomophene-type compounds as monitored by their ability to bind to immature rat uterine cytoplasmic estrogen receptor, transfer receptor sites to the nucleus, and elicit estrogenic responses (increased uterine weight and induction of the synthesis of a specific uterine protein, called induced protein, or \"IP\"), and by their ability to antagonize the effects of estradiol on these receptor interactions and uterine responses. Both CI-628 (CI) and U-11, 100A (UA) [50 mug] elicit slight IP induction at 1-2 hand give pronounced uterine weight increases at 24 h but feeble increases at 72 h (3 single daily injections). Both bind to cytosol, and effect the transfer of receptor sites to the nucleus, which may account for the estrogenicity of these compounds. Both CI and UA give rapid (by 2-4 h), prolonged (for over 24 h), and complete blockage of estradiol-stimulated treatment abolishes short-term estradiol-stimulated uterine weight increase and antagonizes the 72 h estradiol-stimulated uterine weight response to the level attributable to the antiestrogen alone. MER-25, at the same dose (50 mug), had no estrogenic or antiestrogenic activity. Both CI and UA rapidly deplete the cytoplasmic estrogen binding capacity, reducing it to barely detectable levels for 24-42 h. Although during this period, no IP or uterine wet weight response can be elicited by estradiol, administration of saturating levels of [3H]estradiol in vivo or in vitro results in the appearance of considerable [3H]estradiol in the nucleus, bound to a macromolecule sedimenting identically with that of the nuclear receptor-estradiol complex (5.5S) formed in the absence of prior antiestrogen exposure. Hence, the estradiol which becomes bound in the nucleus after antiestrogen is biologically ineffective. The return of IP responsiveness after antiestrogen correlates well with the level of cytoplasmic receptor capable of translocation to the nucleus, and not with the nuclear estradiol uptake capacity, Presumably, then, the antiestrogenic action of CI and UA results from their depletion of cytoplasmic receptor sites and not from their ability to block specific estradiol-nuclear receptor binding per se. These studies indicate that one should be cautious in assuming that the magnitude of an estrogen response is necessarily related to the level of estrogen receptor complex in the nucleus.", "contents": "Antiestrogen action in the uterus: biological ineffectiveness of nuclear bound estradiol after antiestrogen. These studies attempt to analyze the basis of the estrogenic and antiestrogenic action of three nonsteroidal clomophene-type compounds as monitored by their ability to bind to immature rat uterine cytoplasmic estrogen receptor, transfer receptor sites to the nucleus, and elicit estrogenic responses (increased uterine weight and induction of the synthesis of a specific uterine protein, called induced protein, or \"IP\"), and by their ability to antagonize the effects of estradiol on these receptor interactions and uterine responses. Both CI-628 (CI) and U-11, 100A (UA) [50 mug] elicit slight IP induction at 1-2 hand give pronounced uterine weight increases at 24 h but feeble increases at 72 h (3 single daily injections). Both bind to cytosol, and effect the transfer of receptor sites to the nucleus, which may account for the estrogenicity of these compounds. Both CI and UA give rapid (by 2-4 h), prolonged (for over 24 h), and complete blockage of estradiol-stimulated treatment abolishes short-term estradiol-stimulated uterine weight increase and antagonizes the 72 h estradiol-stimulated uterine weight response to the level attributable to the antiestrogen alone. MER-25, at the same dose (50 mug), had no estrogenic or antiestrogenic activity. Both CI and UA rapidly deplete the cytoplasmic estrogen binding capacity, reducing it to barely detectable levels for 24-42 h. Although during this period, no IP or uterine wet weight response can be elicited by estradiol, administration of saturating levels of [3H]estradiol in vivo or in vitro results in the appearance of considerable [3H]estradiol in the nucleus, bound to a macromolecule sedimenting identically with that of the nuclear receptor-estradiol complex (5.5S) formed in the absence of prior antiestrogen exposure. Hence, the estradiol which becomes bound in the nucleus after antiestrogen is biologically ineffective. The return of IP responsiveness after antiestrogen correlates well with the level of cytoplasmic receptor capable of translocation to the nucleus, and not with the nuclear estradiol uptake capacity, Presumably, then, the antiestrogenic action of CI and UA results from their depletion of cytoplasmic receptor sites and not from their ability to block specific estradiol-nuclear receptor binding per se. These studies indicate that one should be cautious in assuming that the magnitude of an estrogen response is necessarily related to the level of estrogen receptor complex in the nucleus."} {"id": "PMID:166822", "title": "Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands.", "content": "The effect of Fibroblast Growth Factor (FGF) on the initiation of DNA synthesis and on the rate of division of the Y1 adrenal cell line has been investigated. In sparse populations of Y1 cells (4 times 10- minus 3 cells/cm2) maintained in 0.2 percent calf serum, FGF was able to initiate DNA synthesis to the same extent that an optimal concentration of serum could. Cells maintained in 0.2 percent calf serum sustained continuous growth when given 5 ng/ml of FGF daily. Cultures fixed and stained with crystal violet showed FGF colonies to be of equivalent size and quantity as those with serum alone. Insulin had no mitogenic activity of its own at concentrations as high as 500 ng/ml nor did it have any potentiating effect on the mitogenic activity of FGF. Glucocorticoids (0.1 mug/ml to 1 mug/ml) inhibited (25 percent) the initiation of DNA synthesis as well as the rate of division induced by FGF. ACTH (0.75 IU/ml) was clearly inhibitory. Not only did it reduce the rate of division of cells in serum but it also reduced the rate of DNA synthesis and inhibited division in the presence of FGF.", "contents": "Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands. The effect of Fibroblast Growth Factor (FGF) on the initiation of DNA synthesis and on the rate of division of the Y1 adrenal cell line has been investigated. In sparse populations of Y1 cells (4 times 10- minus 3 cells/cm2) maintained in 0.2 percent calf serum, FGF was able to initiate DNA synthesis to the same extent that an optimal concentration of serum could. Cells maintained in 0.2 percent calf serum sustained continuous growth when given 5 ng/ml of FGF daily. Cultures fixed and stained with crystal violet showed FGF colonies to be of equivalent size and quantity as those with serum alone. Insulin had no mitogenic activity of its own at concentrations as high as 500 ng/ml nor did it have any potentiating effect on the mitogenic activity of FGF. Glucocorticoids (0.1 mug/ml to 1 mug/ml) inhibited (25 percent) the initiation of DNA synthesis as well as the rate of division induced by FGF. ACTH (0.75 IU/ml) was clearly inhibitory. Not only did it reduce the rate of division of cells in serum but it also reduced the rate of DNA synthesis and inhibited division in the presence of FGF."} {"id": "PMID:166823", "title": "The effect of LH/FSH, dibutyryl cyclic AMP, and prostaglandins on the production of estrogens by rabbit granulosa cells in vitro.", "content": "The purpose of this study was to establish the effects of trophic hormones on the production of estrogens by rabbit granulosa cells. A pure population of these cells was isolated from preovulatory follicles (1-15 mm in diameter) of estrous rabbits, and cultured for 6 days with either one or a combination of the following hormones: androstenedione, Pergonal (LH/FSH), dibutyryl cyclic AMP (Bu2cAMP), prostaglandin F2alpha (PGF2alpha), or prostaglandin E2 (PGE2). The medium was collected every 2 days and progesterone (P), estrone (E1) and estradiol-17 beta (E2beta) were measured by radioimmunoassay. Granulosa cells cultured as controls (i.e., without exogenous trophic hormones) secreted P spontaneously and its secretion was stimulated 100 to 1,000 fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. Androstenedione, either alone or with trophic hormones had no apparent effect on the cytology of the granulosa cells or their ability to secrete P. In the absence of exogenous androstenedione, the cultures produced very small amounts of E1 or E2beta (smaller than 100 pg/ml), either spontaneously or in response to LH/FSH, B12cAMP, PGF2alpha, or PGE2. Incubating granulosa cells with exogenous androstenedione (1 mug/ml) resulted in a 30- to 150-fold increase in E2beta production, which was stimulated an additional 3- to 5-fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. In most cultures, E2beta production was restricted to the first 2 days in vitro. Bu2cAMP, however, maintained E2beta production at relatively high levels throughout the duration of the experiment, but there was a progressive decrease in its production. The production of E1 was only 5 percent of E2beta, but the pattern of secretion was similar for both estrogens. These results suggest that cyclic AMP could have a role in regulating the synthesis of estrogens by rabbit granulosa cells.", "contents": "The effect of LH/FSH, dibutyryl cyclic AMP, and prostaglandins on the production of estrogens by rabbit granulosa cells in vitro. The purpose of this study was to establish the effects of trophic hormones on the production of estrogens by rabbit granulosa cells. A pure population of these cells was isolated from preovulatory follicles (1-15 mm in diameter) of estrous rabbits, and cultured for 6 days with either one or a combination of the following hormones: androstenedione, Pergonal (LH/FSH), dibutyryl cyclic AMP (Bu2cAMP), prostaglandin F2alpha (PGF2alpha), or prostaglandin E2 (PGE2). The medium was collected every 2 days and progesterone (P), estrone (E1) and estradiol-17 beta (E2beta) were measured by radioimmunoassay. Granulosa cells cultured as controls (i.e., without exogenous trophic hormones) secreted P spontaneously and its secretion was stimulated 100 to 1,000 fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. Androstenedione, either alone or with trophic hormones had no apparent effect on the cytology of the granulosa cells or their ability to secrete P. In the absence of exogenous androstenedione, the cultures produced very small amounts of E1 or E2beta (smaller than 100 pg/ml), either spontaneously or in response to LH/FSH, B12cAMP, PGF2alpha, or PGE2. Incubating granulosa cells with exogenous androstenedione (1 mug/ml) resulted in a 30- to 150-fold increase in E2beta production, which was stimulated an additional 3- to 5-fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. In most cultures, E2beta production was restricted to the first 2 days in vitro. Bu2cAMP, however, maintained E2beta production at relatively high levels throughout the duration of the experiment, but there was a progressive decrease in its production. The production of E1 was only 5 percent of E2beta, but the pattern of secretion was similar for both estrogens. These results suggest that cyclic AMP could have a role in regulating the synthesis of estrogens by rabbit granulosa cells."} {"id": "PMID:166824", "title": "Comparison of the binding of human chorionic gonadotropin to isolated bovine luteal cells and bovine luteal plasma membranes.", "content": "The specific binding of [125-I]iodohCG to intact luteal cells obtained from bovine corpus luteum by enzymatic treatment, or to purified plasma membranes obtained from bovine corpus luteum has been compared. It was a saturable process with respect to the [125-]iodohCG concentration. Specific binding could be detected at concentrations as low as 1.8 ng of HCG per ml and saturation achieved at 92 ng/ml. The [125-I]iodohCG specifically bound to the luteal cells or to the plasma membranes was displaced by increasing concentrations of native hCG. Subunits hCGalpha and beta had respectively 200- and 800-fold less activity than hCG. Four to 10 times more ovine LH than hCG was required to displace an identical amount of bound [125-I]iodohCG. The binding of hCG to its receptor site was a function of time and temperature. The affinity of hCG for its receptor sites in luteal cells or plasma membranes of luteal cells was similar (dissociation constants of 5.3 and 3.8 times 10- minus 10 M, respectively). The number of sites per luteal cell was 5 times 10-4 and the capacity of plasma membranes to bind hCG was 140 fmol per mg of protein at saturation. The data does not, however, allow a comparison between the number of binding sites in the two preparations. It is concluded that the enzymatic treatment necessary to obtain a suspension of viable luteal cells does not affect the kinetic characteristics of the binding of hCG to receptor sites since they are similar to those of plasma membranes not treated with proteolytic enzymes.", "contents": "Comparison of the binding of human chorionic gonadotropin to isolated bovine luteal cells and bovine luteal plasma membranes. The specific binding of [125-I]iodohCG to intact luteal cells obtained from bovine corpus luteum by enzymatic treatment, or to purified plasma membranes obtained from bovine corpus luteum has been compared. It was a saturable process with respect to the [125-]iodohCG concentration. Specific binding could be detected at concentrations as low as 1.8 ng of HCG per ml and saturation achieved at 92 ng/ml. The [125-I]iodohCG specifically bound to the luteal cells or to the plasma membranes was displaced by increasing concentrations of native hCG. Subunits hCGalpha and beta had respectively 200- and 800-fold less activity than hCG. Four to 10 times more ovine LH than hCG was required to displace an identical amount of bound [125-I]iodohCG. The binding of hCG to its receptor site was a function of time and temperature. The affinity of hCG for its receptor sites in luteal cells or plasma membranes of luteal cells was similar (dissociation constants of 5.3 and 3.8 times 10- minus 10 M, respectively). The number of sites per luteal cell was 5 times 10-4 and the capacity of plasma membranes to bind hCG was 140 fmol per mg of protein at saturation. The data does not, however, allow a comparison between the number of binding sites in the two preparations. It is concluded that the enzymatic treatment necessary to obtain a suspension of viable luteal cells does not affect the kinetic characteristics of the binding of hCG to receptor sites since they are similar to those of plasma membranes not treated with proteolytic enzymes."} {"id": "PMID:166825", "title": "The mechanism of ACTH stimulation of adrenal ornithine decarboxylase activity.", "content": "The mechanism of action of adrenocorticotrophin (ACTH) stimulation of rat adrenal orticotrophin (ACTH) stimulation of rat adrenal ornithine decarboxylase activity was investigated. ACTH induction or ornithine decarboxylase activity was not prevented by administration of drugs that inhibit adrenal steroid biosynthesis. A dose of ACTH that produced maximal levels of adrenal cyclic AMP did not induce ornthine decarboxylase activity. Ovine growth hormone, which caused no increase in adrenal cyclic AMP, stimulated adrenal ornithine decarboxyase activity. These observations suggest that the increase in adrenal ornithine decarboxylase activity stimulated by ACTH is not dependent upon steroidogenesis, nor is it dependent on the early peak of cyclic AMP, although it may be influenced by the sustained levels of tissue cyclic AMP that follow the administration of large doses of ACTH. Furthermore, it appears there may be a pathway of ornithine decarboxylase activation in the adrenal which is entirely independent of cyclic AMP mediation. The effects of hypophysectomy on adrenal ornithine decarboxylase response to ACTH were examined. In rats given ACTH 16 h after hypophysectomy, the increase in ornithine decarboxylase activity was delayed when compared with the response in animals given ACTH 1 h after hypophysectomy. Actinomycin D given during the first 3 h after ACTH in the 16 h hypophysectomized rat abolished the expected increase in ornithine decarboxylase activity. Thereafter, a progressive increase in ornithine decarboxylase activity was observed as the interval between ACTH and Actinomycin D administration was further increased. In contrast, Actinomycin D administered 15 min before ACTH in the 1 h hypophysectomized rat had no effect on the subsequent increase in ornithine decarboxylase activity, and actually progressively enhanced the response the longer its administration after ACTH was delayed. Cycloheximide abolished the response to ACTH in both the 1 h and the 16 h hypophysectomized rat. Thus, it appears that ACTH stimulates a post-transcriptional mechanism regulating ornithine decarboxylase activity in the acutely hypophysectomized animal, whereas, in the chronically hypophysectomized rat, ACTH must first stimulate transcription of new messenger RNA which is involved in regulation of adrenal ornithine decarboxylase synthesis.", "contents": "The mechanism of ACTH stimulation of adrenal ornithine decarboxylase activity. The mechanism of action of adrenocorticotrophin (ACTH) stimulation of rat adrenal orticotrophin (ACTH) stimulation of rat adrenal ornithine decarboxylase activity was investigated. ACTH induction or ornithine decarboxylase activity was not prevented by administration of drugs that inhibit adrenal steroid biosynthesis. A dose of ACTH that produced maximal levels of adrenal cyclic AMP did not induce ornthine decarboxylase activity. Ovine growth hormone, which caused no increase in adrenal cyclic AMP, stimulated adrenal ornithine decarboxyase activity. These observations suggest that the increase in adrenal ornithine decarboxylase activity stimulated by ACTH is not dependent upon steroidogenesis, nor is it dependent on the early peak of cyclic AMP, although it may be influenced by the sustained levels of tissue cyclic AMP that follow the administration of large doses of ACTH. Furthermore, it appears there may be a pathway of ornithine decarboxylase activation in the adrenal which is entirely independent of cyclic AMP mediation. The effects of hypophysectomy on adrenal ornithine decarboxylase response to ACTH were examined. In rats given ACTH 16 h after hypophysectomy, the increase in ornithine decarboxylase activity was delayed when compared with the response in animals given ACTH 1 h after hypophysectomy. Actinomycin D given during the first 3 h after ACTH in the 16 h hypophysectomized rat abolished the expected increase in ornithine decarboxylase activity. Thereafter, a progressive increase in ornithine decarboxylase activity was observed as the interval between ACTH and Actinomycin D administration was further increased. In contrast, Actinomycin D administered 15 min before ACTH in the 1 h hypophysectomized rat had no effect on the subsequent increase in ornithine decarboxylase activity, and actually progressively enhanced the response the longer its administration after ACTH was delayed. Cycloheximide abolished the response to ACTH in both the 1 h and the 16 h hypophysectomized rat. Thus, it appears that ACTH stimulates a post-transcriptional mechanism regulating ornithine decarboxylase activity in the acutely hypophysectomized animal, whereas, in the chronically hypophysectomized rat, ACTH must first stimulate transcription of new messenger RNA which is involved in regulation of adrenal ornithine decarboxylase synthesis."} {"id": "PMID:166826", "title": "Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat.", "content": "The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.", "contents": "Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat. The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid."} {"id": "PMID:166827", "title": "Effects of TSH on iodide transport by mouse thyroid lobes in vitro.", "content": "Thyroidal iodide concentration by in vitro mouse thyroid lobes was studied by determining the equilibrium tissue/medium iodide, concentration ratio (T/M[I-]), THYROIDAL I- influx, and thyroidal I-efflux in the presence and absence of ClO4-. Chronic thyroid stimulation by low dietary iodine increased the T/M[I-], and the increase was linearly related to I- influx. There was no difference in efflux rate when animals fed low and high iodine diets were compared, although the efflux with C104- added to block influx was increased by low iodine diet. Addition of TSH in vitro caused a delayed fall in T/M[I-] with a similar TSH concentration-dependence as colloid droplet formation. The TSH effect was mimicked by exogenous cyclic AMP but could be dissociated from stimulation of hormone release by colchicine. Thyroidal I- efflux was increased up to 20-fold by C104-. In the presence of C104- short-term and equilibrium-labeled I- exited at the same rate, but in the absence of C104- short-term-labeled I- efflux was consistently higher. The TSH-induced fall in T/M I- could be accounted for by increased iodide efflux. As TSH also increased efflux when influx was blocked by C104-, the TSH effect would seem due to an increased intrinsic follicular leakiness.", "contents": "Effects of TSH on iodide transport by mouse thyroid lobes in vitro. Thyroidal iodide concentration by in vitro mouse thyroid lobes was studied by determining the equilibrium tissue/medium iodide, concentration ratio (T/M[I-]), THYROIDAL I- influx, and thyroidal I-efflux in the presence and absence of ClO4-. Chronic thyroid stimulation by low dietary iodine increased the T/M[I-], and the increase was linearly related to I- influx. There was no difference in efflux rate when animals fed low and high iodine diets were compared, although the efflux with C104- added to block influx was increased by low iodine diet. Addition of TSH in vitro caused a delayed fall in T/M[I-] with a similar TSH concentration-dependence as colloid droplet formation. The TSH effect was mimicked by exogenous cyclic AMP but could be dissociated from stimulation of hormone release by colchicine. Thyroidal I- efflux was increased up to 20-fold by C104-. In the presence of C104- short-term and equilibrium-labeled I- exited at the same rate, but in the absence of C104- short-term-labeled I- efflux was consistently higher. The TSH-induced fall in T/M I- could be accounted for by increased iodide efflux. As TSH also increased efflux when influx was blocked by C104-, the TSH effect would seem due to an increased intrinsic follicular leakiness."} {"id": "PMID:166828", "title": "Effects of lithium on vasopressin-dependent cyclic AMP in rat renal medulla.", "content": "A vasopressin resistant urinary concentrating defect has been described in patients receiving lithium salt for affective disorders. For the pathogenic mechanism of the concentrating defect it has been postulated that lithium inhibits the vasopressin-dependent cyclic AMP system. However, the results of indirect studies on the lithium effect are equivocal. Therefore, the effect of lithium specifically on the vasopressin-dependent cyclic AMP system was investigated in rat renal medulla. The increase of cyclic AMP concentration by vasopressin was inhibited by lithium. But lithium had no effect on the PTH-dependent cyclic AMP concentration in renal cortical slices. Regardless of magnesium concentrations from 0-10 mM in the incubation media, 10 mM lithium had no moeasurable effect on the vasopressin-dependent adenylate cyclase of rat renal medulla. However, 10 mM lithium augmented the cyclic AMP-phosphodiesterase activity in renal medulla in the high Km system. These results suggest that lithium inhibits the vasopressin-dependent cyclic AMP concentration in renal medulla via the augmentation of its catabolism, rather than via the inhibition of cyclic AMP generation.", "contents": "Effects of lithium on vasopressin-dependent cyclic AMP in rat renal medulla. A vasopressin resistant urinary concentrating defect has been described in patients receiving lithium salt for affective disorders. For the pathogenic mechanism of the concentrating defect it has been postulated that lithium inhibits the vasopressin-dependent cyclic AMP system. However, the results of indirect studies on the lithium effect are equivocal. Therefore, the effect of lithium specifically on the vasopressin-dependent cyclic AMP system was investigated in rat renal medulla. The increase of cyclic AMP concentration by vasopressin was inhibited by lithium. But lithium had no effect on the PTH-dependent cyclic AMP concentration in renal cortical slices. Regardless of magnesium concentrations from 0-10 mM in the incubation media, 10 mM lithium had no moeasurable effect on the vasopressin-dependent adenylate cyclase of rat renal medulla. However, 10 mM lithium augmented the cyclic AMP-phosphodiesterase activity in renal medulla in the high Km system. These results suggest that lithium inhibits the vasopressin-dependent cyclic AMP concentration in renal medulla via the augmentation of its catabolism, rather than via the inhibition of cyclic AMP generation."} {"id": "PMID:166829", "title": "New evidence for an acute role of protein kinase in hCG action.", "content": "The present experiments were designed to study whether exogenous hCG could elicit acute changes in the ovarian concentration of soluble cAMP-dependent protein kinases temporally related to binding of hCG and intracellular accumulation of cAMP. Cyclic AMP dependent protein kinase activity decreased five-fold within 5 to 30 min after intravenous administration of highly purified hCG to pseudopregnant rats. Moreover cAMP dependent protein kinase activity was totally suppressed with 0.5 IU hCG, whereas tissue concentration of cAMP continued to increase throughout the dose range (0.05-5.0 IU) of hCG used in the present studies. A marked fall in cAMP-dependent protein kinase activity had occurred before there was a significant change in intracellular accumulation of cAMP, possibly reflecting intracellular compartmentalization of cAMP. Inhibitors of protein did not affect the hCG-induced changes in tissue concentrations of cAMP and soluble cAMP dependent protein kinase activity but did suppress the recovery of cAMP dependent protein kinase activity to pretreatment levels. Cyclic AMP dependent protein kinases appear to play a significant role in mediating hormonal action in vivo. In addition the present studies suggest that, protein kinases may protect the cell from excessive hormonal stimulation.", "contents": "New evidence for an acute role of protein kinase in hCG action. The present experiments were designed to study whether exogenous hCG could elicit acute changes in the ovarian concentration of soluble cAMP-dependent protein kinases temporally related to binding of hCG and intracellular accumulation of cAMP. Cyclic AMP dependent protein kinase activity decreased five-fold within 5 to 30 min after intravenous administration of highly purified hCG to pseudopregnant rats. Moreover cAMP dependent protein kinase activity was totally suppressed with 0.5 IU hCG, whereas tissue concentration of cAMP continued to increase throughout the dose range (0.05-5.0 IU) of hCG used in the present studies. A marked fall in cAMP-dependent protein kinase activity had occurred before there was a significant change in intracellular accumulation of cAMP, possibly reflecting intracellular compartmentalization of cAMP. Inhibitors of protein did not affect the hCG-induced changes in tissue concentrations of cAMP and soluble cAMP dependent protein kinase activity but did suppress the recovery of cAMP dependent protein kinase activity to pretreatment levels. Cyclic AMP dependent protein kinases appear to play a significant role in mediating hormonal action in vivo. In addition the present studies suggest that, protein kinases may protect the cell from excessive hormonal stimulation."} {"id": "PMID:166830", "title": "Relationship between ACTH release and corticosterone binding by the receptor sites of the adenohypophysis and dorsal hippocampus following infusion of corticosterone at a constant rate in the adrenalectomized rat.", "content": "The amount of corticosterone bound to proteins in the adenohypophysis and dorsal hippocampus was studied concurrently with the plasma ACTH concentration in 4-week adrenalectomized male rats under steady-state conditions achieved by infusing the steroid at a constant rate for 45 min. Corticosterone binding was measured by gel chromatography on Sephadex LH-20, using a TE buffer containing 0.4 m NaCl. No saturation was observed in whole homogenates and supernatants with increasing plasma corticosterone concentrations. However, corticosterone binding by the pituitary and by one of two types of hippocampal receptors evidenced saturation within our range of corticosterone infusion rates, indeed. Scatchard plots allowed us to distinguish two types of binding sites in the hippocampus. The first, saturated at a low corticosterone concentration has an association constant of 3.0 times 10-8 M-1 with a number of binding sites estimated at 150 times 10- minus 15 mol/mg protein, whereas the second is associated with non-specific binding. The adenohypophysis shows only one kind of binding site with an association constant of 3.6 times 10-8 m- minus 1 and a number of sites estimated at 989 times 10- minus 15 mol/mg protein. A suggestive relationship was observed between ACTH inhibition by corticosterone and saturation of the pituitary binding sites. Our data are consistent with the possible involvement of corticosterone binding by specific sites in the negative feedback regulation of ACTH release.", "contents": "Relationship between ACTH release and corticosterone binding by the receptor sites of the adenohypophysis and dorsal hippocampus following infusion of corticosterone at a constant rate in the adrenalectomized rat. The amount of corticosterone bound to proteins in the adenohypophysis and dorsal hippocampus was studied concurrently with the plasma ACTH concentration in 4-week adrenalectomized male rats under steady-state conditions achieved by infusing the steroid at a constant rate for 45 min. Corticosterone binding was measured by gel chromatography on Sephadex LH-20, using a TE buffer containing 0.4 m NaCl. No saturation was observed in whole homogenates and supernatants with increasing plasma corticosterone concentrations. However, corticosterone binding by the pituitary and by one of two types of hippocampal receptors evidenced saturation within our range of corticosterone infusion rates, indeed. Scatchard plots allowed us to distinguish two types of binding sites in the hippocampus. The first, saturated at a low corticosterone concentration has an association constant of 3.0 times 10-8 M-1 with a number of binding sites estimated at 150 times 10- minus 15 mol/mg protein, whereas the second is associated with non-specific binding. The adenohypophysis shows only one kind of binding site with an association constant of 3.6 times 10-8 m- minus 1 and a number of sites estimated at 989 times 10- minus 15 mol/mg protein. A suggestive relationship was observed between ACTH inhibition by corticosterone and saturation of the pituitary binding sites. Our data are consistent with the possible involvement of corticosterone binding by specific sites in the negative feedback regulation of ACTH release."} {"id": "PMID:166831", "title": "Inhibition of anterior pituitary estrogen-receptor complex formation by low-affinity interaction with 5 alpha-dihydrotestosterone.", "content": "A possible role for 5alpha-dihydrotestosterone in the anterior pituitary of the rat has been investigated by determining the influence of this androgen upon the binding 17beta-estrasiol to its cytoplasmic receptor. Under equilibrium binding conditions, both testosterone and 5 alpha-dihydrotestosterone are very poor competitors for the estrogen binding sites, as compared to estrogenic compounds. 5alpha-Dihydrotestosterone, however, inhibits the initial rate of formation of the estradiol-receptor complex in a concentration-dependent manner. Steroidal specificity of this incubation is indicated by the failure of progesterone to elicit the same effect. The androgen inhibition appears to involve low-affinity interaction with the estrogen receptor, since no high-affinity binding of 5alpha-dihydrotestosterone could be detected. Kinetic analysis indicated that the inhibition is competitive, involving interaction at the estrogen-binding site of the receptor.", "contents": "Inhibition of anterior pituitary estrogen-receptor complex formation by low-affinity interaction with 5 alpha-dihydrotestosterone. A possible role for 5alpha-dihydrotestosterone in the anterior pituitary of the rat has been investigated by determining the influence of this androgen upon the binding 17beta-estrasiol to its cytoplasmic receptor. Under equilibrium binding conditions, both testosterone and 5 alpha-dihydrotestosterone are very poor competitors for the estrogen binding sites, as compared to estrogenic compounds. 5alpha-Dihydrotestosterone, however, inhibits the initial rate of formation of the estradiol-receptor complex in a concentration-dependent manner. Steroidal specificity of this incubation is indicated by the failure of progesterone to elicit the same effect. The androgen inhibition appears to involve low-affinity interaction with the estrogen receptor, since no high-affinity binding of 5alpha-dihydrotestosterone could be detected. Kinetic analysis indicated that the inhibition is competitive, involving interaction at the estrogen-binding site of the receptor."} {"id": "PMID:166832", "title": "Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors.", "content": "Whether the mineralocorticoid effect of glycyrrhetinic acid is mediated by the adrenal glands or is due to a direct action on the renal tubule remains controversial. The affinity of glycyrrhetinic acid for mineralocorticoid receptors has been studied by several types of competition experiments. When rat kidney slices were incubated with 2 times 10- minus 9 M [3H]aldosterone, glycyrrhetinic acid (2 times 10- minus 5 M) was able to compete with aldosterone for the cytosolic receptor and to decrease the formation of a chromatin-[3Hi1 aldosterone-receptor complex. In cytosol, in vitro, 6 times 10- minus 4 M glycyrrhetinic acid was able to inhibit aldosterone binding by 70 percent, whereas the same dose produced only a 20 percent inhibition of dexamethasone binding. The apparent KDiss of glycyrrhetinic acid for the mineralocorticoid receptor was 2 times 10- minus 6 M. That glycyrrhetinic acid appeared to compete mainly with mineralocorticoid receptors was confirmed by sedimentation in the sucrose gradients: [3H]Aldosterone specifically bound to an 8 S peak was displaced by 5 times 10- minus 5 M glycyrrhetinic acid, whereas the [3H]dexamethasone peak was not affected by this compound. Glycyrrhizic acid showed no significant affinity for mineralocorticoid or glucocorticoid kidney receptor sites. Glycyrrhetinic acid and glycyrrhizic acid had no affinity for rat cortisol binding globulin. Glycyrrhetinic acid has a low but definite affinity for mineralocorticoid receptors and thus appears to have a direct mineralocorticoid action. The low affinity of this compound for mineralocorticoid receptors is in good agreement with the very high doses required to exhibit its biological activity.", "contents": "Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors. Whether the mineralocorticoid effect of glycyrrhetinic acid is mediated by the adrenal glands or is due to a direct action on the renal tubule remains controversial. The affinity of glycyrrhetinic acid for mineralocorticoid receptors has been studied by several types of competition experiments. When rat kidney slices were incubated with 2 times 10- minus 9 M [3H]aldosterone, glycyrrhetinic acid (2 times 10- minus 5 M) was able to compete with aldosterone for the cytosolic receptor and to decrease the formation of a chromatin-[3Hi1 aldosterone-receptor complex. In cytosol, in vitro, 6 times 10- minus 4 M glycyrrhetinic acid was able to inhibit aldosterone binding by 70 percent, whereas the same dose produced only a 20 percent inhibition of dexamethasone binding. The apparent KDiss of glycyrrhetinic acid for the mineralocorticoid receptor was 2 times 10- minus 6 M. That glycyrrhetinic acid appeared to compete mainly with mineralocorticoid receptors was confirmed by sedimentation in the sucrose gradients: [3H]Aldosterone specifically bound to an 8 S peak was displaced by 5 times 10- minus 5 M glycyrrhetinic acid, whereas the [3H]dexamethasone peak was not affected by this compound. Glycyrrhizic acid showed no significant affinity for mineralocorticoid or glucocorticoid kidney receptor sites. Glycyrrhetinic acid and glycyrrhizic acid had no affinity for rat cortisol binding globulin. Glycyrrhetinic acid has a low but definite affinity for mineralocorticoid receptors and thus appears to have a direct mineralocorticoid action. The low affinity of this compound for mineralocorticoid receptors is in good agreement with the very high doses required to exhibit its biological activity."} {"id": "PMID:166833", "title": "Antiandrogenic effect of spirolactones: mechanism of action.", "content": "Spirolactones are aldosterone antagonists which inhibit the binding of aldosterone to the renal mineralocorticoid receptor. These molecules also possess an antiandrogenic effect which could be due, among other possibilities, to a peripheral antagonism of androgens. This hypothesis has been tested in the present study. From in vivo experiments, spironolactone K+ canrenoate appear to inhibit the binding of [3H]5alpha-dihydrotestosterone [3H]DHT to the cytosolic and nuclear receptor of the rat ventral prostate. The doses used are in the same range as those used for demonstrating the antimineralocorticoid effect of these molecules. In vitro incubations and in vitro displacement studies show that spironolactone and K+ canrenoate are respectively about 20 and 100 times less effective than DHT in displacing 50 percent of 5 times 10- minus 10 M [3H]DHT from its receptor. Spirolactones are also able to compete with [3H]DHT for the specific 8 S cytosolic receptor. Neither spironolactone nor K+ canrenoate decreases prostatic 5alpha-reductase activity, even at a concentration as high as 10- minus 5 M. It seems likely that spirolactones, besides their action on testosterone biosynthesis, exert their antiandrogenic activity via a peripheral androgen antagonism.", "contents": "Antiandrogenic effect of spirolactones: mechanism of action. Spirolactones are aldosterone antagonists which inhibit the binding of aldosterone to the renal mineralocorticoid receptor. These molecules also possess an antiandrogenic effect which could be due, among other possibilities, to a peripheral antagonism of androgens. This hypothesis has been tested in the present study. From in vivo experiments, spironolactone K+ canrenoate appear to inhibit the binding of [3H]5alpha-dihydrotestosterone [3H]DHT to the cytosolic and nuclear receptor of the rat ventral prostate. The doses used are in the same range as those used for demonstrating the antimineralocorticoid effect of these molecules. In vitro incubations and in vitro displacement studies show that spironolactone and K+ canrenoate are respectively about 20 and 100 times less effective than DHT in displacing 50 percent of 5 times 10- minus 10 M [3H]DHT from its receptor. Spirolactones are also able to compete with [3H]DHT for the specific 8 S cytosolic receptor. Neither spironolactone nor K+ canrenoate decreases prostatic 5alpha-reductase activity, even at a concentration as high as 10- minus 5 M. It seems likely that spirolactones, besides their action on testosterone biosynthesis, exert their antiandrogenic activity via a peripheral androgen antagonism."} {"id": "PMID:166834", "title": "Modulation by thyroid hormones of cytoplasmic estrogen receptor concentrations in reproductive tissues of the rat.", "content": "The influence of induced variations in circulating levels of thyroid hormones upon the estrogen receptor content of rat uterine, anterior pituitary and hypothalamic cytosol fractions has been investigated. Sucrose gradient centrifugation analyses showed no observable effects of thyroidectomy or acute induced hyperthyroidism upon receptor levels in uterus hypothalamus of ovariectomized rats, but an apparent positive thyroidal influence upon anterior pituitary receptor content. Qualitatively, the receptor complex sedimentation coefficients were unaltered. Binding assays showed that thyroid hormone administration to the ovariectomized rat resulted in a marked increase in pituitary receptor content, whereas the same treatment had no significant effect on the pituitary receptor level of the intact animal. Conversely, a marked fall in uterine receptor content was found in thyroxine-treated intact, but not castrate, animals. The changes in measurable receptor levels could not be attributed to competition for estrogen binding sites by thyroxine or triiodothyronine. Pituitary receptor content of ovariectomized rats was studied following administration of varying levels of thyroxine; 5 mug/day significantly depressed receptor levels, while enhancement of binding capacity was occasioned by levels of thyroxine ewual to or greather than 25 mug/day. The hypothalamus was completely unaffected by similar treatment and the uterus responded with decreased receptor level only at the highest dosage used. Thyroxine replacement reversed the decrease in anterior pituitary receptor concentration detectable following thyroidectomy. The effect of the thyroid hormones on the pituitary receptor content was not a result of changes in the capability of the tissue to respond to estrogen-induced synthesis of receptor.", "contents": "Modulation by thyroid hormones of cytoplasmic estrogen receptor concentrations in reproductive tissues of the rat. The influence of induced variations in circulating levels of thyroid hormones upon the estrogen receptor content of rat uterine, anterior pituitary and hypothalamic cytosol fractions has been investigated. Sucrose gradient centrifugation analyses showed no observable effects of thyroidectomy or acute induced hyperthyroidism upon receptor levels in uterus hypothalamus of ovariectomized rats, but an apparent positive thyroidal influence upon anterior pituitary receptor content. Qualitatively, the receptor complex sedimentation coefficients were unaltered. Binding assays showed that thyroid hormone administration to the ovariectomized rat resulted in a marked increase in pituitary receptor content, whereas the same treatment had no significant effect on the pituitary receptor level of the intact animal. Conversely, a marked fall in uterine receptor content was found in thyroxine-treated intact, but not castrate, animals. The changes in measurable receptor levels could not be attributed to competition for estrogen binding sites by thyroxine or triiodothyronine. Pituitary receptor content of ovariectomized rats was studied following administration of varying levels of thyroxine; 5 mug/day significantly depressed receptor levels, while enhancement of binding capacity was occasioned by levels of thyroxine ewual to or greather than 25 mug/day. The hypothalamus was completely unaffected by similar treatment and the uterus responded with decreased receptor level only at the highest dosage used. Thyroxine replacement reversed the decrease in anterior pituitary receptor concentration detectable following thyroidectomy. The effect of the thyroid hormones on the pituitary receptor content was not a result of changes in the capability of the tissue to respond to estrogen-induced synthesis of receptor."} {"id": "PMID:166835", "title": "Premature regression of corpora lutea in pseudopregnant rabbits following the removal of polydimethylsiloxane capsules containing 17 beta-estradiol.", "content": "17-beta-Estradiol, which is luteotropic in rabbits, was administered during pseudopregnancy via polydimethylsiloxane (Silastic) implants to determine the effects on serum progesterone concentrations. Implants which released estradiol at a rate of approximately 2 mug/day were place beneath the skin the day after sterile mating and ovulation (day 0). Blood (3 ml) was obtained from the marginal ear vein on days 3, 6, 9, 10, 11 and 12. Serum estradiol levels, determined by radioimmunoassay, were 2- to 3-fold higher in estradiol-treated rabbits (11.7 plus or minus 1.2 pg/ml) than in untreated pseudopregnant controls (5.9 plus or minus 1.4 pg/ml). Weights of corpora lutea in treated and control rabbits were not different at the conclusion of the experiment on day 12. Serum progesterone concentrations, also determined by radioimmunoassay, were not significantly different between treated and control animals. However, when estradiol implants were removed from other rabbits on day 10, a rapid decline in serum progesterone occurred, from 14.0 plus or minus 2.4 to 2.6 plus or minus 0.8 ng/ml 24 h later. By comparison, serum progesterone concentrations in rabbits with estradiol implants left in place and in untreated rabbits on day 12 were similar (similar to 12 ng/ml). The premature decline in serum progesterone was accompanied by a decrease in the wet weight of corpora lutea. Other experiments revealed: 1) a precipitous fall in serum estradiol to basal values within 2 h after estradiol implants were removed, preceding the decline in serum progesterone by approximately 6 to 10 h; 2) reduced levels of estradiol in ovarian venous blood, but elevated levels of estradiol in peripheral arterial blood of rabbits with estradiol impants. The inability to elevated estradiol to increase serum progesterone or weights of corpora litea suggests that the luteotropic effect is maximal when estradiol is present at physiological concentrations. Following the continuous administration of estradiol, ovarian secretion of estradiol appears diminished and the corpora lutea become dependent upon the exogenous estradiol for luteotropic support. Although the ovaries continue to release measureable quantities of estradiol, this is inmeasurable quantities of estradiol, this is insufficient to prevent regression of corpora lutea when exogenous estradiol is rapidly withdrawn from the circulation.", "contents": "Premature regression of corpora lutea in pseudopregnant rabbits following the removal of polydimethylsiloxane capsules containing 17 beta-estradiol. 17-beta-Estradiol, which is luteotropic in rabbits, was administered during pseudopregnancy via polydimethylsiloxane (Silastic) implants to determine the effects on serum progesterone concentrations. Implants which released estradiol at a rate of approximately 2 mug/day were place beneath the skin the day after sterile mating and ovulation (day 0). Blood (3 ml) was obtained from the marginal ear vein on days 3, 6, 9, 10, 11 and 12. Serum estradiol levels, determined by radioimmunoassay, were 2- to 3-fold higher in estradiol-treated rabbits (11.7 plus or minus 1.2 pg/ml) than in untreated pseudopregnant controls (5.9 plus or minus 1.4 pg/ml). Weights of corpora lutea in treated and control rabbits were not different at the conclusion of the experiment on day 12. Serum progesterone concentrations, also determined by radioimmunoassay, were not significantly different between treated and control animals. However, when estradiol implants were removed from other rabbits on day 10, a rapid decline in serum progesterone occurred, from 14.0 plus or minus 2.4 to 2.6 plus or minus 0.8 ng/ml 24 h later. By comparison, serum progesterone concentrations in rabbits with estradiol implants left in place and in untreated rabbits on day 12 were similar (similar to 12 ng/ml). The premature decline in serum progesterone was accompanied by a decrease in the wet weight of corpora lutea. Other experiments revealed: 1) a precipitous fall in serum estradiol to basal values within 2 h after estradiol implants were removed, preceding the decline in serum progesterone by approximately 6 to 10 h; 2) reduced levels of estradiol in ovarian venous blood, but elevated levels of estradiol in peripheral arterial blood of rabbits with estradiol impants. The inability to elevated estradiol to increase serum progesterone or weights of corpora litea suggests that the luteotropic effect is maximal when estradiol is present at physiological concentrations. Following the continuous administration of estradiol, ovarian secretion of estradiol appears diminished and the corpora lutea become dependent upon the exogenous estradiol for luteotropic support. Although the ovaries continue to release measureable quantities of estradiol, this is inmeasurable quantities of estradiol, this is insufficient to prevent regression of corpora lutea when exogenous estradiol is rapidly withdrawn from the circulation."} {"id": "PMID:166838", "title": "Influence of ionic strength of incubation medium on the release of some enzymes from rat liver mitochondria.", "content": "Influence of ionic strength of incubation medium on the release of adenylate kinase (AK), isocitrate dehydrogenase (IDH) and glutamate dehydrogenase (GDH) from intact and injured rat liver mitochondria has been studied. It has been found that raised ionic strength (mu equal 0.16-0.32) has increased the release of GDH and AK activities - IDH to a lesser degree - for mitochondrial preparations only with damaged inner membrane. Treatment of mitochondria with potassium chloride solution of definite ionic strength has permitted to detect the alteration of these organelles occurring in vivo and in vitro.", "contents": "Influence of ionic strength of incubation medium on the release of some enzymes from rat liver mitochondria. Influence of ionic strength of incubation medium on the release of adenylate kinase (AK), isocitrate dehydrogenase (IDH) and glutamate dehydrogenase (GDH) from intact and injured rat liver mitochondria has been studied. It has been found that raised ionic strength (mu equal 0.16-0.32) has increased the release of GDH and AK activities - IDH to a lesser degree - for mitochondrial preparations only with damaged inner membrane. Treatment of mitochondria with potassium chloride solution of definite ionic strength has permitted to detect the alteration of these organelles occurring in vivo and in vitro."} {"id": "PMID:166839", "title": "The effect of dietary rape-seed oil on cholesterol-ester metabolism and cholesterol-ester-hydrolase activity in the rat adrenal.", "content": "The effects of stock diet and stock diet supplemented by olive oil and rape seed on rat adrenal cholesterol ester metabolism have been studied. Rats fed rape seed oil failed to gain weight at the same rate as rats fed olive oil. A prominent feature of the rats fed rape seed oil was an accumulation of high concentrations of cholesterol erucate in the adrenal lipid droplets. When these rats were subjected to an ether stress no percentage decrease in the amount of cholesterol erucate was observed. Adrenal cholesterol ester hydrolase activity was higher in rats fed the olive oil and rape seed oil diets than rats fed the stock diet. In rats fed stock or olive oil diets, a ten-minute ether anaesthesia stress resulted in a two-fold increase in activity of adrenal cholesterol ester hydrolase. Cofactor addition of ATP, cyclic AMP and MgCl-2 in vitro resulted in a stimulation of cholesterol ester hydrolase to a similar activity in both quiescent and ether-stressed rats. By contrast rats fed the rape seed oil diet gave no significant stimulation of cholesterol ester hydrolase activity when given an ether stress or when cofactors were added in vitro. Cholesterol erucate was hydrolysed at only 25% to 30% of the rate of cholesterol oleate in vitro in all groups of animals. Oleic acid added in vitro gave an inhibition of cholesterol ester hydrolase activity in rats fed stock diet while erucic acid activated the enzyme. The accumulation of cholesterol erucate in the adrenal when rats are fed rape seed oil could be due to the reduced ability of cholesterol ester hydrolase to hydrolyse this ester.", "contents": "The effect of dietary rape-seed oil on cholesterol-ester metabolism and cholesterol-ester-hydrolase activity in the rat adrenal. The effects of stock diet and stock diet supplemented by olive oil and rape seed on rat adrenal cholesterol ester metabolism have been studied. Rats fed rape seed oil failed to gain weight at the same rate as rats fed olive oil. A prominent feature of the rats fed rape seed oil was an accumulation of high concentrations of cholesterol erucate in the adrenal lipid droplets. When these rats were subjected to an ether stress no percentage decrease in the amount of cholesterol erucate was observed. Adrenal cholesterol ester hydrolase activity was higher in rats fed the olive oil and rape seed oil diets than rats fed the stock diet. In rats fed stock or olive oil diets, a ten-minute ether anaesthesia stress resulted in a two-fold increase in activity of adrenal cholesterol ester hydrolase. Cofactor addition of ATP, cyclic AMP and MgCl-2 in vitro resulted in a stimulation of cholesterol ester hydrolase to a similar activity in both quiescent and ether-stressed rats. By contrast rats fed the rape seed oil diet gave no significant stimulation of cholesterol ester hydrolase activity when given an ether stress or when cofactors were added in vitro. Cholesterol erucate was hydrolysed at only 25% to 30% of the rate of cholesterol oleate in vitro in all groups of animals. Oleic acid added in vitro gave an inhibition of cholesterol ester hydrolase activity in rats fed stock diet while erucic acid activated the enzyme. The accumulation of cholesterol erucate in the adrenal when rats are fed rape seed oil could be due to the reduced ability of cholesterol ester hydrolase to hydrolyse this ester."} {"id": "PMID:166840", "title": "Control of pyrimidine biosynthesis in the perfused liver. Feedback inhibition of glutamine-dependent carbamoyl phosphate synthetase.", "content": "The site of feedback inhibition of the biosynthesis of pyrimidine nucleotides de novo was investigated in the isolated perfused rat liver. Hepatic uridine phosphate contents were specifically depleted by use of D-galactosamine. The effective activities of enzymes involved in the synthetic pathway were deduced from the rats of incorporation of labeled precursors into the acid-soluble uracil nucleotide pool and into some intermediates of the pathway. The labeling of hepatic urea was also monitored. When the uridine phosphate contents were less than 20% of controls, the incorporation of [14-C]-bicarbonate was stimulated about 20-fold. Label from [U-14C]oxaloacetate used as permeable precursor of intrace-lular aspartate was introduced into the uridylates to the same extent in normal and UTP-depleted livers. Similar results were obtained with labeled carbamoyl phosphate although the uptake of this compound by the liver was rather low. The lack of labeling of urea from exogenous carbamoyl phosphate does not indicate a free exchange of extra- and intramitochondrial carbamoyl phosphate. [ureido-14C]Ureidosuccinate produced in normal and D-galactosamine-treated livers almost identical labeling patterns of dihydroorotate, orotate and orotidine 5'-phosphate. The steady state concentrations of these intermediates were all below 15 nmol/g liver wet weight.", "contents": "Control of pyrimidine biosynthesis in the perfused liver. Feedback inhibition of glutamine-dependent carbamoyl phosphate synthetase. The site of feedback inhibition of the biosynthesis of pyrimidine nucleotides de novo was investigated in the isolated perfused rat liver. Hepatic uridine phosphate contents were specifically depleted by use of D-galactosamine. The effective activities of enzymes involved in the synthetic pathway were deduced from the rats of incorporation of labeled precursors into the acid-soluble uracil nucleotide pool and into some intermediates of the pathway. The labeling of hepatic urea was also monitored. When the uridine phosphate contents were less than 20% of controls, the incorporation of [14-C]-bicarbonate was stimulated about 20-fold. Label from [U-14C]oxaloacetate used as permeable precursor of intrace-lular aspartate was introduced into the uridylates to the same extent in normal and UTP-depleted livers. Similar results were obtained with labeled carbamoyl phosphate although the uptake of this compound by the liver was rather low. The lack of labeling of urea from exogenous carbamoyl phosphate does not indicate a free exchange of extra- and intramitochondrial carbamoyl phosphate. [ureido-14C]Ureidosuccinate produced in normal and D-galactosamine-treated livers almost identical labeling patterns of dihydroorotate, orotate and orotidine 5'-phosphate. The steady state concentrations of these intermediates were all below 15 nmol/g liver wet weight."} {"id": "PMID:166841", "title": "Modification of phenylalanyl-tRNA synthetase from baker's yeast by proteolytic cleavage and properties of the trypsin-modified enzyme.", "content": "Earlier studies have shown that native phenylalanyl-tRNA synthetase from baker's yeast contains two different kinds of subunits, alpha of molecular weight 73000 and beta of molecular weight 63000. The enzyme is an asymmetric tetramer alpha-2beta-2, which binds two moles of each ligand per mole. Incubation of the purified enzyme with trypsin results in an irreversible conversion: the alpha-subunit remains apparently unchanged but beta is rapidly degraded and yields a lighter species beta of molecular weight 41000. The trypsin-modified enzyme is an alpha-2beta-2 molecule which can still activate phenylalanine but cannot transfer it to tRNA-Phe; furthermore it does not bind tRNA-Phe but its kinetic parameters are identical to those of the native enzyme with respect to ATP and phenylalanine. Therefore the two beta subunits play a critical part in tRNA binding. Isolated alpha or beta subunits exhibit no significant activity and both types of subunit seem to be required for phenylalanine activation.", "contents": "Modification of phenylalanyl-tRNA synthetase from baker's yeast by proteolytic cleavage and properties of the trypsin-modified enzyme. Earlier studies have shown that native phenylalanyl-tRNA synthetase from baker's yeast contains two different kinds of subunits, alpha of molecular weight 73000 and beta of molecular weight 63000. The enzyme is an asymmetric tetramer alpha-2beta-2, which binds two moles of each ligand per mole. Incubation of the purified enzyme with trypsin results in an irreversible conversion: the alpha-subunit remains apparently unchanged but beta is rapidly degraded and yields a lighter species beta of molecular weight 41000. The trypsin-modified enzyme is an alpha-2beta-2 molecule which can still activate phenylalanine but cannot transfer it to tRNA-Phe; furthermore it does not bind tRNA-Phe but its kinetic parameters are identical to those of the native enzyme with respect to ATP and phenylalanine. Therefore the two beta subunits play a critical part in tRNA binding. Isolated alpha or beta subunits exhibit no significant activity and both types of subunit seem to be required for phenylalanine activation."} {"id": "PMID:166842", "title": "Characterization of the reaction between ferrocytochrome c and cytochrome c oxidase.", "content": "The reaction between cytochrome c oxidase and ferrocytochrome c has been investigated by the stopped-flow method. It has been found that only one electron acceptor, a heme group, in the oxidase is rapidly reduced by cytochrome c. The presence of N3- does not affect the reduction of the acceptor, which supports the hypothesis that this is identical with cytochrome a. The results are consistent with the existence of a simple equilibrium between cytochrome a and cytochrome c: c-2 + a-3+ in equilibrium c-3+ + a-2+ with an equilibrium constant corresponding to an oxidation-reduction potential of cytochrome a 30 mV higher than that for cytochrome c at pH 7.4. The oxidation-reduction potential of the a-3+ /a-2+ couple, 285 mV (based on a potential of 255 mV for cytochrome c), and the optical properties of the reduced form indicate that it is identical with neither of the reduced hemes seen in potentiometric titrations. The oxidase species resulting from the rapid reduction of cytochrome a by cytochrome c is proposed to represent a metastable intermediate state which, under anaerobic conditions, eventually is transformed into a more stable state characterized by a reduced high-potential heme.", "contents": "Characterization of the reaction between ferrocytochrome c and cytochrome c oxidase. The reaction between cytochrome c oxidase and ferrocytochrome c has been investigated by the stopped-flow method. It has been found that only one electron acceptor, a heme group, in the oxidase is rapidly reduced by cytochrome c. The presence of N3- does not affect the reduction of the acceptor, which supports the hypothesis that this is identical with cytochrome a. The results are consistent with the existence of a simple equilibrium between cytochrome a and cytochrome c: c-2 + a-3+ in equilibrium c-3+ + a-2+ with an equilibrium constant corresponding to an oxidation-reduction potential of cytochrome a 30 mV higher than that for cytochrome c at pH 7.4. The oxidation-reduction potential of the a-3+ /a-2+ couple, 285 mV (based on a potential of 255 mV for cytochrome c), and the optical properties of the reduced form indicate that it is identical with neither of the reduced hemes seen in potentiometric titrations. The oxidase species resulting from the rapid reduction of cytochrome a by cytochrome c is proposed to represent a metastable intermediate state which, under anaerobic conditions, eventually is transformed into a more stable state characterized by a reduced high-potential heme."} {"id": "PMID:166843", "title": "Cyclic amp concentration and enzyme activities of cerebrospinal fluid in patients with epilepsy or central nervous system damage.", "content": "Cyclic adenosine-3',5'-monophosphate (cAMP) concentration in cerebrospinal fluid (CSF) was measured by the protein binding method of Gilman from 62 neurological patients, 46 of them were epileptics and 16 with a central nervous system (CNS) damage. In epileptic patients the CSF concentration of cAMP was significantly elevated (p smaller than 0.02) for 3 days after an attack when compared with those free from attacks for at least 2 weeks. The causality relationship between the rise of cAMP in CSF and an epileptic discharge is discussed. In patient with an active or rapidly progressing CNS damage the cAMP levels in the CSF were significantly higher (p smaller than 0.001) than in those with an old CNS damage. Also some enzyme activities in CSF were measured but no uniform alterations could be found. In damaging processes of the CNS, the cAMP values in the CSF seem to correlate to the activity of the disease.", "contents": "Cyclic amp concentration and enzyme activities of cerebrospinal fluid in patients with epilepsy or central nervous system damage. Cyclic adenosine-3',5'-monophosphate (cAMP) concentration in cerebrospinal fluid (CSF) was measured by the protein binding method of Gilman from 62 neurological patients, 46 of them were epileptics and 16 with a central nervous system (CNS) damage. In epileptic patients the CSF concentration of cAMP was significantly elevated (p smaller than 0.02) for 3 days after an attack when compared with those free from attacks for at least 2 weeks. The causality relationship between the rise of cAMP in CSF and an epileptic discharge is discussed. In patient with an active or rapidly progressing CNS damage the cAMP levels in the CSF were significantly higher (p smaller than 0.001) than in those with an old CNS damage. Also some enzyme activities in CSF were measured but no uniform alterations could be found. In damaging processes of the CNS, the cAMP values in the CSF seem to correlate to the activity of the disease."} {"id": "PMID:166844", "title": "Evidence for disordered cyclic amp metabolism in patients with cerebral infarction.", "content": "Systemic blood cyclic AMP levels were elevated but urinary excretion was unaltered in patients with recent cerebral infarction. Cerebral venous levels for cyclic AMP were significantly higher than arterial levels. CSF cyclic AMP levels were also elevated. After intravenous 10% glycerol, CSF cyclic AMP levels decreased and cerebral A-V differences were reduced. Elevation of cyclic AMP levels in plasma may be due to alteration of neuroendocrinal function after cerebral infraction and contributed to in part by release from infarcted brain. Cyclic AMP release into cerebral venous blood and CSF suggests (1) blood brain barrier damage and (2) extracellular cyclic AMP accumulation in infarcted brain secondary to abnormal neurotransmitter release and/or impaired cellular function which appears to be partially reversed by glycerol.", "contents": "Evidence for disordered cyclic amp metabolism in patients with cerebral infarction. Systemic blood cyclic AMP levels were elevated but urinary excretion was unaltered in patients with recent cerebral infarction. Cerebral venous levels for cyclic AMP were significantly higher than arterial levels. CSF cyclic AMP levels were also elevated. After intravenous 10% glycerol, CSF cyclic AMP levels decreased and cerebral A-V differences were reduced. Elevation of cyclic AMP levels in plasma may be due to alteration of neuroendocrinal function after cerebral infraction and contributed to in part by release from infarcted brain. Cyclic AMP release into cerebral venous blood and CSF suggests (1) blood brain barrier damage and (2) extracellular cyclic AMP accumulation in infarcted brain secondary to abnormal neurotransmitter release and/or impaired cellular function which appears to be partially reversed by glycerol."} {"id": "PMID:166871", "title": "[Research on substances with antiviral activity. II. Derivatives of N-substituted 2-chloro-3-formylindoles].", "content": "Thiosemicarbazones and amidinohydrazones of N-substituted 2-chloroindole-3-aldehydes were synthesized and investigated for antiviral activity against RNA virus (parainfluenza type 3, HA-I/CR-8 stock) and DNA virus (vaccinia virus, HID stock). The thiosemicarbazones of 1-(o,m,p,-chlorobenzoyl)-2-chloroindole-3-aldehydes were more active than methisazone against vaccinia virus.", "contents": "[Research on substances with antiviral activity. II. Derivatives of N-substituted 2-chloro-3-formylindoles]. Thiosemicarbazones and amidinohydrazones of N-substituted 2-chloroindole-3-aldehydes were synthesized and investigated for antiviral activity against RNA virus (parainfluenza type 3, HA-I/CR-8 stock) and DNA virus (vaccinia virus, HID stock). The thiosemicarbazones of 1-(o,m,p,-chlorobenzoyl)-2-chloroindole-3-aldehydes were more active than methisazone against vaccinia virus."} {"id": "PMID:166892", "title": "[The role of ACTH in the process of complex heparin compound formation in the blood during immobilization stress].", "content": "In rats during stress due to 30 min immobilization the total unenzymatic fibrinolytic activity becomes 4 times as high, and its share in the blood plasma total fibrinolytic activity 1.5 times as high. The same stress with ACTH added up increases these values still more: by 2.5 times. ACTH considerably increases formation of the heparin complexes also in absence of the stress. The ACTH effect on the heparin complexes formation is mediated through adrenal stimulation. In 96 hr after adrenalectomy the additional cortical tissue already responds to ACTH administration and, respectively, the stressor effect with ACTH added up entails still greater increase of the unenzymatic fibrinolytic activity than without ACTH.", "contents": "[The role of ACTH in the process of complex heparin compound formation in the blood during immobilization stress]. In rats during stress due to 30 min immobilization the total unenzymatic fibrinolytic activity becomes 4 times as high, and its share in the blood plasma total fibrinolytic activity 1.5 times as high. The same stress with ACTH added up increases these values still more: by 2.5 times. ACTH considerably increases formation of the heparin complexes also in absence of the stress. The ACTH effect on the heparin complexes formation is mediated through adrenal stimulation. In 96 hr after adrenalectomy the additional cortical tissue already responds to ACTH administration and, respectively, the stressor effect with ACTH added up entails still greater increase of the unenzymatic fibrinolytic activity than without ACTH."} {"id": "PMID:166895", "title": "Prevention of hypoglycemic attacks by propranolol in a patient suffering from insulinoma.", "content": "An insulinoma was diagnosed in a fifty-seven-year-old woman suffering from frequent hypoglycemic attacks. Propranolol--a beta-adrenergic blocker--in a dose of 80 mg. per day effectively prevented recurrent hypoglycemic attacks. It also corrected the basal hyperinsulinemia as well as the increased insulin secretion which results from stimulation with glucose or arginine.", "contents": "Prevention of hypoglycemic attacks by propranolol in a patient suffering from insulinoma. An insulinoma was diagnosed in a fifty-seven-year-old woman suffering from frequent hypoglycemic attacks. Propranolol--a beta-adrenergic blocker--in a dose of 80 mg. per day effectively prevented recurrent hypoglycemic attacks. It also corrected the basal hyperinsulinemia as well as the increased insulin secretion which results from stimulation with glucose or arginine."} {"id": "PMID:166896", "title": "Degradation of insulin by isolated rat liver cells.", "content": "The degradation of insulin by isolated rat liver cells has been studied. The phenomenon is time- and temperature-dependent. After sixty minutes' exposure to 1.5 times 10-6 cells/ml, about 50 per cent, 15 per cent, and less than 5 per cent of insulin at 1.5 muM. are degraded at 37 degrees C., 20 degrees, and 0 degrees C., respectively. The methods used to measure the hormone degradation effect the apparent Vmax. Higher values of Vmax are found when radioimmunoassay rather than precipitation by trichloracetic acid and absorption to talc is used. However, the apparent Km. (0.27 muM) is virtually the same with any of methods used. N-ethyl-maleimide and Trasylol are potent inhibitors, whereas GSH increases the hormone degradation. Proinsulin acts as competitive inhibitor (apparent Ki equals 0.35 muM.). Gel filtration patterns of incubation supernates suggest that several enzymatic systems may be operative in the degradation of insulin by the liver cells. Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic similiarities with insulin proteases, suggest that a proteolytic mechanism is involved. The insulin-degrading system in isolated liver cells closely resembles that observed in purified liver plasma membranes and in the isolated perfused liver. Such similarities stress the possible significance of the degradation process in the regulation of insulin action. These studies are also important for the quantitative analysis of insulin interaction with its specific receptors in isolated liver cells.", "contents": "Degradation of insulin by isolated rat liver cells. The degradation of insulin by isolated rat liver cells has been studied. The phenomenon is time- and temperature-dependent. After sixty minutes' exposure to 1.5 times 10-6 cells/ml, about 50 per cent, 15 per cent, and less than 5 per cent of insulin at 1.5 muM. are degraded at 37 degrees C., 20 degrees, and 0 degrees C., respectively. The methods used to measure the hormone degradation effect the apparent Vmax. Higher values of Vmax are found when radioimmunoassay rather than precipitation by trichloracetic acid and absorption to talc is used. However, the apparent Km. (0.27 muM) is virtually the same with any of methods used. N-ethyl-maleimide and Trasylol are potent inhibitors, whereas GSH increases the hormone degradation. Proinsulin acts as competitive inhibitor (apparent Ki equals 0.35 muM.). Gel filtration patterns of incubation supernates suggest that several enzymatic systems may be operative in the degradation of insulin by the liver cells. Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic similiarities with insulin proteases, suggest that a proteolytic mechanism is involved. The insulin-degrading system in isolated liver cells closely resembles that observed in purified liver plasma membranes and in the isolated perfused liver. Such similarities stress the possible significance of the degradation process in the regulation of insulin action. These studies are also important for the quantitative analysis of insulin interaction with its specific receptors in isolated liver cells."} {"id": "PMID:166898", "title": "Synthesis of proinsulin and large glucagon immunoreactivity in isolated Langerhans islets from EMC-virus infected mice.", "content": "The protein synthesis in normal and in EMC-virus infected mouse islets of Langerhans was investigated. Mouse large glucagon immunoreactivity was determined by an immunoassay after chromatographic separation. It was characterized as a peptide of 16 000 MW with in intracellular half-life of 35-45 min. The proportional reduction of void volume proteins, large glucagon immunoreactivity and proinsulin synthesis after infection shows, that both alpha- and beta-cells are damaged by the virus. A reduction in the synthesis of the three protein fractions was already found 6 hrs after inoculation of the virus and remained nearly constant for 48 hrs. An almost complete breakdown of protein synthesis occurred 60 to 70 hrs after infection and was paralleled by the first light microscopic changes in the islets. The stimulation of proinsulin synthesis by glucose was preserved for 48 hrs after EMC-virus infection.", "contents": "Synthesis of proinsulin and large glucagon immunoreactivity in isolated Langerhans islets from EMC-virus infected mice. The protein synthesis in normal and in EMC-virus infected mouse islets of Langerhans was investigated. Mouse large glucagon immunoreactivity was determined by an immunoassay after chromatographic separation. It was characterized as a peptide of 16 000 MW with in intracellular half-life of 35-45 min. The proportional reduction of void volume proteins, large glucagon immunoreactivity and proinsulin synthesis after infection shows, that both alpha- and beta-cells are damaged by the virus. A reduction in the synthesis of the three protein fractions was already found 6 hrs after inoculation of the virus and remained nearly constant for 48 hrs. An almost complete breakdown of protein synthesis occurred 60 to 70 hrs after infection and was paralleled by the first light microscopic changes in the islets. The stimulation of proinsulin synthesis by glucose was preserved for 48 hrs after EMC-virus infection."} {"id": "PMID:166899", "title": "The mechanism of alloxan toxicity: an indication for alloxan complexes in tissues and alloxan inhibition of 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid (SITS) binding for the liver cell membrane.", "content": "It is shown that alloxan inhibits binding of SITS to liver cells. This indicates the cell membrane as a site of alloxan action. Alloxan is found to react with tissues to form complexes that are detectable up to 3 hrs after alloxan treatment. On the basis of the present findings, an assumption is made that alloxan inhibits a cell membrane processes by blockade of functionally importnat groups.", "contents": "The mechanism of alloxan toxicity: an indication for alloxan complexes in tissues and alloxan inhibition of 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid (SITS) binding for the liver cell membrane. It is shown that alloxan inhibits binding of SITS to liver cells. This indicates the cell membrane as a site of alloxan action. Alloxan is found to react with tissues to form complexes that are detectable up to 3 hrs after alloxan treatment. On the basis of the present findings, an assumption is made that alloxan inhibits a cell membrane processes by blockade of functionally importnat groups."} {"id": "PMID:166900", "title": "Electroencephalographic changes with age in male mice.", "content": "Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging.", "contents": "Electroencephalographic changes with age in male mice. Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging."} {"id": "PMID:166901", "title": "Biochemical and histochemical changes in energy supply enzyme pattern of muscles of the rat during old age.", "content": "Senile muscles of the rat (28-36 months) show loss of overall activity of glycolytic and aerobic enzymes. However, there is a differential loss and shift of enzyme activity pattern in the three types of muscles. The extensor digitorum longus (EDL) and diaphragm show a decrease of ratios of glycolytic to aerobic-oxidative enzymes. This shift to a more oxidative type of metabolism is not observed in the soleus muscle. Decrease of enzyme activities is least marked in the diaphragm muscle. Biochemical analysis shows a trend to levelling out of metabolic differences between the different muscle types. This trend of 'dedifferentiation' is most marked when comparing EDL and soleus, least marked when comparing EDL and diaphragm muscle. The histochemical analysis shows a shift from the original mixed to a more uniform pattern of muscle fibres in the EDL and soleus muscle; this levelling-out of differences between enzymatic activities of different muscle fibres is not observed in the diaphragm muscle. Preferential atrophy and loss of ATPase activity in II muscle fibres in the soleus muscle and the occurrence of 'type grouping' are further characteristic features of senile muscle change. The findings show general (i.e. loss of enzyme activities) and differential trends of biochemical and histochemical enzyme changes in different types of muscles.", "contents": "Biochemical and histochemical changes in energy supply enzyme pattern of muscles of the rat during old age. Senile muscles of the rat (28-36 months) show loss of overall activity of glycolytic and aerobic enzymes. However, there is a differential loss and shift of enzyme activity pattern in the three types of muscles. The extensor digitorum longus (EDL) and diaphragm show a decrease of ratios of glycolytic to aerobic-oxidative enzymes. This shift to a more oxidative type of metabolism is not observed in the soleus muscle. Decrease of enzyme activities is least marked in the diaphragm muscle. Biochemical analysis shows a trend to levelling out of metabolic differences between the different muscle types. This trend of 'dedifferentiation' is most marked when comparing EDL and soleus, least marked when comparing EDL and diaphragm muscle. The histochemical analysis shows a shift from the original mixed to a more uniform pattern of muscle fibres in the EDL and soleus muscle; this levelling-out of differences between enzymatic activities of different muscle fibres is not observed in the diaphragm muscle. Preferential atrophy and loss of ATPase activity in II muscle fibres in the soleus muscle and the occurrence of 'type grouping' are further characteristic features of senile muscle change. The findings show general (i.e. loss of enzyme activities) and differential trends of biochemical and histochemical enzyme changes in different types of muscles."} {"id": "PMID:166904", "title": "A case of syndactyly in the white-lipped tamarin Saguinus nigricollis.", "content": "A case of syndactyly in a captive bred white-lipped tamarin (Saguinus nigricollis) is reported which involved the fusion of metacarpals 3 and 4 of both hands. Variations in the vertebral formula among the parents and offspring were also found.", "contents": "A case of syndactyly in the white-lipped tamarin Saguinus nigricollis. A case of syndactyly in a captive bred white-lipped tamarin (Saguinus nigricollis) is reported which involved the fusion of metacarpals 3 and 4 of both hands. Variations in the vertebral formula among the parents and offspring were also found."} {"id": "PMID:166905", "title": "[Carotid angiography with subtraction for glomus tumours of the middle ear (author's transl)].", "content": "Four patients with glomus tumours of the middle ear are described, in whom carotid angiography with subtraction was carried out. In three patients the tumour could be clearly demonstrated by using the subtraction method. In a fourth case, in whom the diagnosis was made at operation, angiography was unsuccessful.", "contents": "[Carotid angiography with subtraction for glomus tumours of the middle ear (author's transl)]. Four patients with glomus tumours of the middle ear are described, in whom carotid angiography with subtraction was carried out. In three patients the tumour could be clearly demonstrated by using the subtraction method. In a fourth case, in whom the diagnosis was made at operation, angiography was unsuccessful."} {"id": "PMID:166906", "title": "The value of fine needle aspiration biopsy and intravenous pyelography in the diagnosis of renal masses.", "content": "On the basis of an analysis in 118 patients with space occupying lesions in the kidney demonstrated on the pyelogram it is conluded, that the combination of intravenous pyelography and fine needle aspiration biopsy is a safe diagnostic procedure, and it could be a valuable supplement to angiography and explorative incision.", "contents": "The value of fine needle aspiration biopsy and intravenous pyelography in the diagnosis of renal masses. On the basis of an analysis in 118 patients with space occupying lesions in the kidney demonstrated on the pyelogram it is conluded, that the combination of intravenous pyelography and fine needle aspiration biopsy is a safe diagnostic procedure, and it could be a valuable supplement to angiography and explorative incision."} {"id": "PMID:166908", "title": "Using volunteer therapists to reduce hospital readmissions.", "content": "Two aftercare programs using volunteers as therapists for former inpatients have been effective in reducing hospital readmissions. The volunteer therapists ensure that patients take medications, evaluate them for decompensation, help them find housing and jobs, and give them supportive counseling. In the first program the recidivism rate after one year for 36 chronic schizophrenic women was 11 per cent for the group treated by volunteers and 34 per cent for the control group receiving traditional aftercare. In the second program the recidivism rate after one year for 11 men and women with various types of schizophrenia was 9 per cent for the treatment group and 37 per cent for the control group.", "contents": "Using volunteer therapists to reduce hospital readmissions. Two aftercare programs using volunteers as therapists for former inpatients have been effective in reducing hospital readmissions. The volunteer therapists ensure that patients take medications, evaluate them for decompensation, help them find housing and jobs, and give them supportive counseling. In the first program the recidivism rate after one year for 36 chronic schizophrenic women was 11 per cent for the group treated by volunteers and 34 per cent for the control group receiving traditional aftercare. In the second program the recidivism rate after one year for 11 men and women with various types of schizophrenia was 9 per cent for the treatment group and 37 per cent for the control group."} {"id": "PMID:166909", "title": "The placement of long-term \"criminally insane\" patients in open settings.", "content": "Twenty long-term psychiatric patients with criminal charges against them were transferred from the Iowa Security Medical Facility to open hospitals and aftercare settings between 1969 and 1971. Staff prepared the patients for transfer and persuaded authorities to permit the placements. Follow-up shows 19 have adapted to the new settings. The authors speculate that age is a factor in predicting aftercare adjustment; 18 of the 19 patients were at least 44 years old. The authors also feel that clinical staff must take the initiative to reduce the needless confinement of such patients.", "contents": "The placement of long-term \"criminally insane\" patients in open settings. Twenty long-term psychiatric patients with criminal charges against them were transferred from the Iowa Security Medical Facility to open hospitals and aftercare settings between 1969 and 1971. Staff prepared the patients for transfer and persuaded authorities to permit the placements. Follow-up shows 19 have adapted to the new settings. The authors speculate that age is a factor in predicting aftercare adjustment; 18 of the 19 patients were at least 44 years old. The authors also feel that clinical staff must take the initiative to reduce the needless confinement of such patients."} {"id": "PMID:166911", "title": "Serum and tissue proteins in tuberous sclerosis. I. Serum and red-cell polymorphic systems.", "content": "5 serum protein polymorphic systems (haptoglobin, alkaline phosphatase, group-specific (Gc) proteins, beta2-glycoprotein 1 and leucine aminopeptidase) and 6 red-cell polymorphisms (adenosine deaminase, adenylate kinase, phosphoglucomutase, glutamic-pyruvic transaminase, phosphogluconate dehydrogenase and acid phosphatase) have been investigated in 54 subjects with tuberous sclerosis. The frequencies of all systems were compared with those of a control sample drawn from a similar mentally retarded population and abnormal distributions were detected in the haptoglobin and Gc system. Quantitative estimation of the serum levels of the Gc protein failed to detect any inter-group differences. Data on the deviations from the Hardy-Weinberg equlibrium, Haldane's Log ratio test between groups, and gene frequencies of both test and control groups are given. It is suggested that selection by mortality is the possible causation for the abnormal distribution of the Gc phenotypes, but the haptoglobin phenotype distribution requires further investigation with care being taken in the selection of control subjects.", "contents": "Serum and tissue proteins in tuberous sclerosis. I. Serum and red-cell polymorphic systems. 5 serum protein polymorphic systems (haptoglobin, alkaline phosphatase, group-specific (Gc) proteins, beta2-glycoprotein 1 and leucine aminopeptidase) and 6 red-cell polymorphisms (adenosine deaminase, adenylate kinase, phosphoglucomutase, glutamic-pyruvic transaminase, phosphogluconate dehydrogenase and acid phosphatase) have been investigated in 54 subjects with tuberous sclerosis. The frequencies of all systems were compared with those of a control sample drawn from a similar mentally retarded population and abnormal distributions were detected in the haptoglobin and Gc system. Quantitative estimation of the serum levels of the Gc protein failed to detect any inter-group differences. Data on the deviations from the Hardy-Weinberg equlibrium, Haldane's Log ratio test between groups, and gene frequencies of both test and control groups are given. It is suggested that selection by mortality is the possible causation for the abnormal distribution of the Gc phenotypes, but the haptoglobin phenotype distribution requires further investigation with care being taken in the selection of control subjects."} {"id": "PMID:166912", "title": "Red cell enzyme polymorphisms in the greek populations.", "content": "The frequency of variant forms of 6 red cell enzymes, adenylate kinase, adenosine deaminase, phosphoglucomutase, acid phosphatase, 6-phosphogluconate dehydrogenase and glutathione reductase, were determined in 9 Greek populations. The frequencies of the variants in these populations were similar to those previously reported in most other European populations. However, several differences, particularly in the 6-phosphogluconate dehydrogenase, phosphoglucomutase and acid phosphatase alleles, were found in a comparison of Greeks and Bulgarians, in accordance with their separate ethnic origins. The Macedonians resembled the other Greeks and differed from the Bulgarians.", "contents": "Red cell enzyme polymorphisms in the greek populations. The frequency of variant forms of 6 red cell enzymes, adenylate kinase, adenosine deaminase, phosphoglucomutase, acid phosphatase, 6-phosphogluconate dehydrogenase and glutathione reductase, were determined in 9 Greek populations. The frequencies of the variants in these populations were similar to those previously reported in most other European populations. However, several differences, particularly in the 6-phosphogluconate dehydrogenase, phosphoglucomutase and acid phosphatase alleles, were found in a comparison of Greeks and Bulgarians, in accordance with their separate ethnic origins. The Macedonians resembled the other Greeks and differed from the Bulgarians."} {"id": "PMID:166913", "title": "Cytogenetic studies in 12 patients with itai-itai disease.", "content": "Among 12 Itai-Itai disease patients examined, 8 patients showed a remarkably high frequency of chromatid aberrations, whereas the other 4 patients showed a much lower frequency of such aberrations, although a significant number of stable type aberrations was observed also in the latter patients. The frequencies of aneuploid cells of all 12 patients were significantly higher than those of the controls. The abnormalities were found in 50-hour and 72-hour cultures, from which it can be concluded that the aberrations occurred in the blood stem cell of the patients. In addition to these structural and numerical aberrations, satellite associations of the D and G group chromosomes were often observed.", "contents": "Cytogenetic studies in 12 patients with itai-itai disease. Among 12 Itai-Itai disease patients examined, 8 patients showed a remarkably high frequency of chromatid aberrations, whereas the other 4 patients showed a much lower frequency of such aberrations, although a significant number of stable type aberrations was observed also in the latter patients. The frequencies of aneuploid cells of all 12 patients were significantly higher than those of the controls. The abnormalities were found in 50-hour and 72-hour cultures, from which it can be concluded that the aberrations occurred in the blood stem cell of the patients. In addition to these structural and numerical aberrations, satellite associations of the D and G group chromosomes were often observed."} {"id": "PMID:166914", "title": "Immunochemical studies on the human pathogen Sporothrix schenckii: effects of chemical and enzymatic modification of the antigenic compounds upon immediate and delayed reactions.", "content": "The rhamnose-containing polysaccharide-peptide compound derived from the cells of the pathogenic fungus Sporothrix schenckii has been shown to contain 87.1% carbohydrate and 12.5% peptide and to give rise to both immediate- and delayed-type reactions in sensitized guinea pigs. The capacity to induce immediate-type reaction, passive cutaneous anaphylaxis, was completely lost by degradation of the carbohydrate moiety by periodate, whereas the ability to induce the delayed-type reactions of migration inhibition (in vitro) and the sporotrichin reaction (in vivo) were only slightly affected by periodate treatment. On the other hand, delayed \"reactivities\" to the compound were considerably reduced by treatment with papain, whereas the immediate-type reaction remained positive. These results lead to a conclusion that the rhamnose-containing polysaccharide of the polysaccharide-peptide antigenic compound plays an important role in the immediate-type reaction, whereas the peptide is largely responsible for the delayed-type reaction.", "contents": "Immunochemical studies on the human pathogen Sporothrix schenckii: effects of chemical and enzymatic modification of the antigenic compounds upon immediate and delayed reactions. The rhamnose-containing polysaccharide-peptide compound derived from the cells of the pathogenic fungus Sporothrix schenckii has been shown to contain 87.1% carbohydrate and 12.5% peptide and to give rise to both immediate- and delayed-type reactions in sensitized guinea pigs. The capacity to induce immediate-type reaction, passive cutaneous anaphylaxis, was completely lost by degradation of the carbohydrate moiety by periodate, whereas the ability to induce the delayed-type reactions of migration inhibition (in vitro) and the sporotrichin reaction (in vivo) were only slightly affected by periodate treatment. On the other hand, delayed \"reactivities\" to the compound were considerably reduced by treatment with papain, whereas the immediate-type reaction remained positive. These results lead to a conclusion that the rhamnose-containing polysaccharide of the polysaccharide-peptide antigenic compound plays an important role in the immediate-type reaction, whereas the peptide is largely responsible for the delayed-type reaction."} {"id": "PMID:166915", "title": "Production, isolation, and partial characterization of three foot-and-mouth disease virus temperature-sensitive mutants.", "content": "Three high temperature-sensitive (ts) mutants of foot-and-mouth disease virus were characterized by their relative abilities to grow at 33 or 38.5 C, to kill infant mice, to infect guinea pigs, and to produce foot-and-mouth disease in steers. Mutants ts-24 and ts-42 did not grow at 38.5 C; both may have produced considerable quantities of noninfectious virus particles at 33 C. A third mutant, ts-22, appeared \"leaky\" because it multiplied to a limited extent during prolonged incubation at the nonpermissive temperature. Mutant ts-42 was pathogenic for infant mice, whereas ts-22 and ts-24 were essentially apathogenic. Mice were protected against the lethal effects of the wild-type (wt) virus if injected 1 week earlier with ts-22, apparently as a result of specific antibody development. One-half of the guinea pigs injected with the mutant viruses showed lesion development, but only at the site of injection. Antibody development was also much less than in those animals injected with the wt virus. The onset of FMD in steers was delayed and the severity of the disease was diminished after intradermalingual injection of the mutant viruses.", "contents": "Production, isolation, and partial characterization of three foot-and-mouth disease virus temperature-sensitive mutants. Three high temperature-sensitive (ts) mutants of foot-and-mouth disease virus were characterized by their relative abilities to grow at 33 or 38.5 C, to kill infant mice, to infect guinea pigs, and to produce foot-and-mouth disease in steers. Mutants ts-24 and ts-42 did not grow at 38.5 C; both may have produced considerable quantities of noninfectious virus particles at 33 C. A third mutant, ts-22, appeared \"leaky\" because it multiplied to a limited extent during prolonged incubation at the nonpermissive temperature. Mutant ts-42 was pathogenic for infant mice, whereas ts-22 and ts-24 were essentially apathogenic. Mice were protected against the lethal effects of the wild-type (wt) virus if injected 1 week earlier with ts-22, apparently as a result of specific antibody development. One-half of the guinea pigs injected with the mutant viruses showed lesion development, but only at the site of injection. Antibody development was also much less than in those animals injected with the wt virus. The onset of FMD in steers was delayed and the severity of the disease was diminished after intradermalingual injection of the mutant viruses."} {"id": "PMID:166916", "title": "Immunological sequelae of Trichinella spiralis infection in mice: effect on the antibody responses to sheep erythrocytes and Japanse B encephalitis virus.", "content": "Immunosuppression of the antibody response to Japanese B encephalitis (JBE) virus and sheep erythrocytes (SRBC) was observed in mice infected with Trichinella spiralis. This suppression was paralleled by the presence of fewer antibody-forming cells to SRBC in the spleens of parasitized mice. Both primary and secondary complement-fixing antibody responses to JBE virus were suppressed, but the development of immunological memory was not affected. Parasitized mice demonstrated a normal blastogenic response to phytohemagglutinin and normal serum clearance rate of injected (125)I-labeled immunoglobulin G(2b), although the size of the extravascular fluid compartment was significantly increased. The data presented here and in previous reports suggest that sequential antigenic competition is a possible explanation for the humoral immunosuppression to heterologous antigens caused by T. spiralis infection.", "contents": "Immunological sequelae of Trichinella spiralis infection in mice: effect on the antibody responses to sheep erythrocytes and Japanse B encephalitis virus. Immunosuppression of the antibody response to Japanese B encephalitis (JBE) virus and sheep erythrocytes (SRBC) was observed in mice infected with Trichinella spiralis. This suppression was paralleled by the presence of fewer antibody-forming cells to SRBC in the spleens of parasitized mice. Both primary and secondary complement-fixing antibody responses to JBE virus were suppressed, but the development of immunological memory was not affected. Parasitized mice demonstrated a normal blastogenic response to phytohemagglutinin and normal serum clearance rate of injected (125)I-labeled immunoglobulin G(2b), although the size of the extravascular fluid compartment was significantly increased. The data presented here and in previous reports suggest that sequential antigenic competition is a possible explanation for the humoral immunosuppression to heterologous antigens caused by T. spiralis infection."} {"id": "PMID:166917", "title": "Interactions between aerolysin, erythrocytes, and erythrocyte membranes.", "content": "Aerolysin, a hemolytic and lethal exotoxin of Aeromonas hydrophila, was analyzed for amino acids. Assuming 8 histidine residues/mol, the purified toxic protein has, by summation, a molecular weight of 49,000, a value in agreement with earlier estimates by other methods. Erythrocytes from different animal species differ greatly in sensitivity to aerolysin's lytic action. There is some correlation between sensitivity and phosphatidyl choline content. Erythrocyte membranes of different species bind the toxin, and the efficiency of binding is a function of sensitivity to lysis. Binding is temperature independent, is not dependent upon membrane sialic acid, and is decreased by prior treatment with phospholipase C and proteases. Preparations of aerolysin convert substantial amounts of membrane phosphorus to water-soluble form; the conversion is concentration and temperature dependent. Most of the conversion is attributable to contaminating phospholipase(s) that is separable from the toxin. Aerolysin purified by electrophoresis in polyacrylamide gel retains some phospholipase activity, and this activity may or may not be a contaminant.", "contents": "Interactions between aerolysin, erythrocytes, and erythrocyte membranes. Aerolysin, a hemolytic and lethal exotoxin of Aeromonas hydrophila, was analyzed for amino acids. Assuming 8 histidine residues/mol, the purified toxic protein has, by summation, a molecular weight of 49,000, a value in agreement with earlier estimates by other methods. Erythrocytes from different animal species differ greatly in sensitivity to aerolysin's lytic action. There is some correlation between sensitivity and phosphatidyl choline content. Erythrocyte membranes of different species bind the toxin, and the efficiency of binding is a function of sensitivity to lysis. Binding is temperature independent, is not dependent upon membrane sialic acid, and is decreased by prior treatment with phospholipase C and proteases. Preparations of aerolysin convert substantial amounts of membrane phosphorus to water-soluble form; the conversion is concentration and temperature dependent. Most of the conversion is attributable to contaminating phospholipase(s) that is separable from the toxin. Aerolysin purified by electrophoresis in polyacrylamide gel retains some phospholipase activity, and this activity may or may not be a contaminant."} {"id": "PMID:166918", "title": "Adeno-associated virus in adenovirus type 3 conjunctivitis.", "content": "Although human infection with adenovirus-associated virus (AAV) has been demonstrated, there is no evidence that disease results from such infections. The proportion of adenovirus infections which are dual infections with AAV is virtually unknown, since special methods are required to demonstrate infection with AAV. To search for AAV, we re-examined a collection of specimens from 40 persons involved in an epidemic of pharyngoconjunctival fever associated with a swimming pool. Virological and serological studies indicated that the etiological agent was adenovirus type 3. When the 91 original eye, throat, and fecal specimens were re-examined, using methods suitable for detection of adenovirus and AAV, 37 strains of adenovirus type 3 and 35 strains of AAV type 3 (AAV3) were isolated. Surprisingly, 19 AAV3 but only 11 adenovirus isolates were found in eye specimens, whereas adenovirus isolates were equally distributed in all types of specimens. Four AAV3 strains were isolated from adults. Significant (fourfold or greater) rises in AAV3 complement-fixing antibody titers were seen in six of 14 persons shedding AAV3, whereas nine of 10 persons shedding adenovirus type 3 showed significant rises in adenovirus complement-fixing antibody. These results raise the question whether AAV persists better in eyes than adenovirus or that a possible association with conjunctivitis might be present. In contrast to the results in the specimens from the swimming pool epidemic, only one of 36 adenovirus strains isolated in other Seattle-based studies yielded AAV. Complement fixation tests on serial sets of sera collected from 60 children not involved in the swimming pool episode revealed nine AAV2 and 12 AAV3 infections during a 4-year period.", "contents": "Adeno-associated virus in adenovirus type 3 conjunctivitis. Although human infection with adenovirus-associated virus (AAV) has been demonstrated, there is no evidence that disease results from such infections. The proportion of adenovirus infections which are dual infections with AAV is virtually unknown, since special methods are required to demonstrate infection with AAV. To search for AAV, we re-examined a collection of specimens from 40 persons involved in an epidemic of pharyngoconjunctival fever associated with a swimming pool. Virological and serological studies indicated that the etiological agent was adenovirus type 3. When the 91 original eye, throat, and fecal specimens were re-examined, using methods suitable for detection of adenovirus and AAV, 37 strains of adenovirus type 3 and 35 strains of AAV type 3 (AAV3) were isolated. Surprisingly, 19 AAV3 but only 11 adenovirus isolates were found in eye specimens, whereas adenovirus isolates were equally distributed in all types of specimens. Four AAV3 strains were isolated from adults. Significant (fourfold or greater) rises in AAV3 complement-fixing antibody titers were seen in six of 14 persons shedding AAV3, whereas nine of 10 persons shedding adenovirus type 3 showed significant rises in adenovirus complement-fixing antibody. These results raise the question whether AAV persists better in eyes than adenovirus or that a possible association with conjunctivitis might be present. In contrast to the results in the specimens from the swimming pool epidemic, only one of 36 adenovirus strains isolated in other Seattle-based studies yielded AAV. Complement fixation tests on serial sets of sera collected from 60 children not involved in the swimming pool episode revealed nine AAV2 and 12 AAV3 infections during a 4-year period."} {"id": "PMID:166920", "title": "L-arginine elution of measles virus adsorbed on monkey erythrocytes.", "content": "l-Arginine (1 M) eluted measles virus adsorbed on monkey erythrocytes without affecting the infectious and hemagglutinating activities of the virus. This phenomenon was also observed for encephalomyocarditis virus and Newcastle disease virus.", "contents": "L-arginine elution of measles virus adsorbed on monkey erythrocytes. l-Arginine (1 M) eluted measles virus adsorbed on monkey erythrocytes without affecting the infectious and hemagglutinating activities of the virus. This phenomenon was also observed for encephalomyocarditis virus and Newcastle disease virus."} {"id": "PMID:166919", "title": "Occurrence of BK virus and BK virus-specific antibodies in the urine of patients receiving chemotherapy for malignancy.", "content": "Urine specimens from 23 children and 9 adults who were undergoing treatment for malignancy as well as urines from 40 normal individuals were concentrated and examined for evidence of papovavirus infection. Papovavirus particles were detected in 6 of 64 urines examined by electron microscopy. Three of the particle-positive urines induced BK virus-specific immunofluorescence after inoculation of WI38 cells, and three isolations of BK virus were made by inoculation of urines from virus-excreting patients into Vero cells. BK virus-specific hemagglutination-inhibiting and immunofluorescence neutralizing antibodies were found in a majority of urines from adult patients, in about a fifth of pediatric patients, and less often in normal urines. Urines of virus-excreting patients generally had antibodies. In indirect fluorescent antibody tests, BK virus-specific antibodies of the immunoglobulin G class were found in five urine specimens from patients; immunoglobulin A antibodies were not detected in any urine. These data suggest that activation of BK virus is related to immunosuppression and not to transplantation itself and that the occurrence of virus-specific antibodies in urine may be indicative of virus multiplication in the urinary tract.", "contents": "Occurrence of BK virus and BK virus-specific antibodies in the urine of patients receiving chemotherapy for malignancy. Urine specimens from 23 children and 9 adults who were undergoing treatment for malignancy as well as urines from 40 normal individuals were concentrated and examined for evidence of papovavirus infection. Papovavirus particles were detected in 6 of 64 urines examined by electron microscopy. Three of the particle-positive urines induced BK virus-specific immunofluorescence after inoculation of WI38 cells, and three isolations of BK virus were made by inoculation of urines from virus-excreting patients into Vero cells. BK virus-specific hemagglutination-inhibiting and immunofluorescence neutralizing antibodies were found in a majority of urines from adult patients, in about a fifth of pediatric patients, and less often in normal urines. Urines of virus-excreting patients generally had antibodies. In indirect fluorescent antibody tests, BK virus-specific antibodies of the immunoglobulin G class were found in five urine specimens from patients; immunoglobulin A antibodies were not detected in any urine. These data suggest that activation of BK virus is related to immunosuppression and not to transplantation itself and that the occurrence of virus-specific antibodies in urine may be indicative of virus multiplication in the urinary tract."} {"id": "PMID:166921", "title": "Interferon production in mice by the capsular polysaccharide of Klebsiella pneumoniae.", "content": "The capsular polysaccharide of Klebsiella pneumoniae (CPS-K) type 1, Kasuya strain, induces interferon production in the blood of mice when injected intravenously. CPS-K resembles bacterial endotoxin (lipopolysaccharide) in the time pattern of interferon production, with peak levels 2h after injection. CPS-K on a weight basis exhibits a more potent interferon-inducing effect than lipopolysaccharide. The active substance responsible for the interferon-inducing activity of CPS-K is the neutral CPS-K antigen which is antigenically distinct from the O antigen and from acidic CPS-K (the type-specific capsular antigen). Neutral CPS-K from the Kasuya strain has been already found to exhibit a strong adjuvant effect on antibody responses to various antigens in mice. Preparations of neutral CPS-K from other strains of K. pneumoniae, of which adjuvant action is only very weak, exhibit interferon-inducing activity similar to the preparation from the Kasuya strain. Heterologous and homologous tolerance to re-induction of interferon is produced by a prior injection (one each) of LPS, neutral CPS-K, and acidic CPS-K. No simple correlation exists between the inducing and tolerogenic capabilities of these substances.", "contents": "Interferon production in mice by the capsular polysaccharide of Klebsiella pneumoniae. The capsular polysaccharide of Klebsiella pneumoniae (CPS-K) type 1, Kasuya strain, induces interferon production in the blood of mice when injected intravenously. CPS-K resembles bacterial endotoxin (lipopolysaccharide) in the time pattern of interferon production, with peak levels 2h after injection. CPS-K on a weight basis exhibits a more potent interferon-inducing effect than lipopolysaccharide. The active substance responsible for the interferon-inducing activity of CPS-K is the neutral CPS-K antigen which is antigenically distinct from the O antigen and from acidic CPS-K (the type-specific capsular antigen). Neutral CPS-K from the Kasuya strain has been already found to exhibit a strong adjuvant effect on antibody responses to various antigens in mice. Preparations of neutral CPS-K from other strains of K. pneumoniae, of which adjuvant action is only very weak, exhibit interferon-inducing activity similar to the preparation from the Kasuya strain. Heterologous and homologous tolerance to re-induction of interferon is produced by a prior injection (one each) of LPS, neutral CPS-K, and acidic CPS-K. No simple correlation exists between the inducing and tolerogenic capabilities of these substances."} {"id": "PMID:166922", "title": "Inhibition of Herpesvirus hominis replication by human interferon.", "content": "The effect of human interferon on single-cycle replication of Herpesvirus hominis type 1 (HV-1) and vesicular stomatitis virus (VSV) in human foreskin fibroblast cultures (HFF) was studied. After treatment of HFF cultures with low concentrations (58 U) of human interferon, a variable but statistically significant inhibition of HV-1 was observed. At higher concentrations (greater than 95 U) yield reduction of HV in interferon-treated cultures approached that of VSV. Preliminary data indicate that antiviral activity decays more rapidly for HV-1 than for VSV after removal of interferon from cultures.", "contents": "Inhibition of Herpesvirus hominis replication by human interferon. The effect of human interferon on single-cycle replication of Herpesvirus hominis type 1 (HV-1) and vesicular stomatitis virus (VSV) in human foreskin fibroblast cultures (HFF) was studied. After treatment of HFF cultures with low concentrations (58 U) of human interferon, a variable but statistically significant inhibition of HV-1 was observed. At higher concentrations (greater than 95 U) yield reduction of HV in interferon-treated cultures approached that of VSV. Preliminary data indicate that antiviral activity decays more rapidly for HV-1 than for VSV after removal of interferon from cultures."} {"id": "PMID:166923", "title": "Establishment of a nonproductive herpes simplex virus infection in rabbit kidney cells.", "content": "A nonproductive infection of rabbit kidney cells was established with a type 2 strain of herpes simplex virus after incubation of the virus-infected cells at 41 C. Although infectious virus could not be recovered from cells disrupted by freeze-thawing or sonication after incubation at 41 C, spontaneous reactivation of virus growth occurred in 84% of the cultures after lag periods of variable length when cultures of viable cells were transferred to 37 C and incubated. Forty-one percent of the cultures had lag periods of 4 or more days, and 24% had lag periods of 7 or more days. The longest lag period was 45 days. A similar infection was established in WI-38 cells, but attempts to establish the infection in human kidney cells was not successful. This nonproductive infection is being used to study the effects of various physical and chemical agents on herpes simplex virus in a latent state.", "contents": "Establishment of a nonproductive herpes simplex virus infection in rabbit kidney cells. A nonproductive infection of rabbit kidney cells was established with a type 2 strain of herpes simplex virus after incubation of the virus-infected cells at 41 C. Although infectious virus could not be recovered from cells disrupted by freeze-thawing or sonication after incubation at 41 C, spontaneous reactivation of virus growth occurred in 84% of the cultures after lag periods of variable length when cultures of viable cells were transferred to 37 C and incubated. Forty-one percent of the cultures had lag periods of 4 or more days, and 24% had lag periods of 7 or more days. The longest lag period was 45 days. A similar infection was established in WI-38 cells, but attempts to establish the infection in human kidney cells was not successful. This nonproductive infection is being used to study the effects of various physical and chemical agents on herpes simplex virus in a latent state."} {"id": "PMID:166924", "title": "Effect of human leukocyte interferon on vaccinia-and herpes virus-infected cell cultures and monkey corneas.", "content": "Pretreatment of human fibroblast cultures with human leukocyte interferon (HIF, 1,000 IU/ml) resulted in a 24-h delay of virus replication after infection with vaccinia virus and herpes simplex virus type 1 and type 2. Additional HIF treatment 24 h after infection effectively lowered the maximum yield of viral infectivity. Equal results were obtained in simian cells with 3,000 IU of HIF per ml. The spread of two cell-bound herpesviruses, varicella zoster virus and Medical Lake macaque herpesvirus, was inhibited by 2,000 IU of HIF per ml in human fibroblasts and Vero cells, respectively. Varicella zoster virus infectivity was notably reduced by HIF, whereas the latter system showed a low sensitivity. To study the effect of HIF in the infected cornea, keratitis was induced experimentally in both eyes of 12 rhesus monkeys and 12 African green monkeys by inoculation with vaccinia virus and herpes simplex virus, respectively. In each monkey one eye served as a control for the full cycle of disease. In the other eye HIF treatment was initiated prophylactically 15 h before or simultaneously with the challenge virus infection or 6 to 20 h postinfectionally or therapeutically after onset of the disease, and the treatment was continued for 2 to 7 days. Prophylactic and simultaneous administration equally resulted in inhibition of both vaccinia and herpes keratitis. Postinfectional and therapeutic administration of interferon moderated the course of keratitis slightly and shortened the period of virus shedding.", "contents": "Effect of human leukocyte interferon on vaccinia-and herpes virus-infected cell cultures and monkey corneas. Pretreatment of human fibroblast cultures with human leukocyte interferon (HIF, 1,000 IU/ml) resulted in a 24-h delay of virus replication after infection with vaccinia virus and herpes simplex virus type 1 and type 2. Additional HIF treatment 24 h after infection effectively lowered the maximum yield of viral infectivity. Equal results were obtained in simian cells with 3,000 IU of HIF per ml. The spread of two cell-bound herpesviruses, varicella zoster virus and Medical Lake macaque herpesvirus, was inhibited by 2,000 IU of HIF per ml in human fibroblasts and Vero cells, respectively. Varicella zoster virus infectivity was notably reduced by HIF, whereas the latter system showed a low sensitivity. To study the effect of HIF in the infected cornea, keratitis was induced experimentally in both eyes of 12 rhesus monkeys and 12 African green monkeys by inoculation with vaccinia virus and herpes simplex virus, respectively. In each monkey one eye served as a control for the full cycle of disease. In the other eye HIF treatment was initiated prophylactically 15 h before or simultaneously with the challenge virus infection or 6 to 20 h postinfectionally or therapeutically after onset of the disease, and the treatment was continued for 2 to 7 days. Prophylactic and simultaneous administration equally resulted in inhibition of both vaccinia and herpes keratitis. Postinfectional and therapeutic administration of interferon moderated the course of keratitis slightly and shortened the period of virus shedding."} {"id": "PMID:166925", "title": "Herpes simplex virus infection in guinea pigs: an animal model for studying latent and recurrent herpes simplex virus infection.", "content": "Footpad infection of guinea pigs with herpes simplex virus led to an acute local inflammatory reaction, followed by a persistent latent infection of lumbosacral dorsal root ganglia. Spontaneous reactivation of the latent virus occurred, leading to recurrent lesions at the site of the initial infection. Clinical observations and virological studies during the acute latent and recurrent infection are reported.", "contents": "Herpes simplex virus infection in guinea pigs: an animal model for studying latent and recurrent herpes simplex virus infection. Footpad infection of guinea pigs with herpes simplex virus led to an acute local inflammatory reaction, followed by a persistent latent infection of lumbosacral dorsal root ganglia. Spontaneous reactivation of the latent virus occurred, leading to recurrent lesions at the site of the initial infection. Clinical observations and virological studies during the acute latent and recurrent infection are reported."} {"id": "PMID:166926", "title": "Role for cell-mediated immunity in the resistance of mice to subcutaneous herpes simplex virus infection.", "content": "The role of cell-mediated immunity in the resistance of young adult mice to subcutaneous herpes simplex virus (HSV) type I infection was studied in mice receiving immunosuppressive doses of antilymphocyte sera (ALS) or antithymocyte sera (ATS). The effectiveness of these treatments to reduce cell-mediated responses was measured by their ability to prolong the life of allografts transplanted to ALS- or ATS-treated mice. It was found that subcutaneous infection of these mice with HSV resulted in spread of virus from the site of inoculation to the central nervous system. Neutralizing antibody could not be detected in the sera of ALS- or ATS-treated mice after HSV inoculation. Passive transfer of neutralizing antibody to ATS-treated mice did not restore resistance to subcutaneous HSV infection. However, adoptive transfer of HSV-sensitized spleen cells did provide significant protection against infection unless the spleen cells were treated with ATS prior to transfer. These experiments suggest that lymphocytes are involved in a cell-mediated response to subcutaneous HSV infection and demonstrate the importance of a noncompromised immune response in controlling spread of HSV from localized areas of infection.", "contents": "Role for cell-mediated immunity in the resistance of mice to subcutaneous herpes simplex virus infection. The role of cell-mediated immunity in the resistance of young adult mice to subcutaneous herpes simplex virus (HSV) type I infection was studied in mice receiving immunosuppressive doses of antilymphocyte sera (ALS) or antithymocyte sera (ATS). The effectiveness of these treatments to reduce cell-mediated responses was measured by their ability to prolong the life of allografts transplanted to ALS- or ATS-treated mice. It was found that subcutaneous infection of these mice with HSV resulted in spread of virus from the site of inoculation to the central nervous system. Neutralizing antibody could not be detected in the sera of ALS- or ATS-treated mice after HSV inoculation. Passive transfer of neutralizing antibody to ATS-treated mice did not restore resistance to subcutaneous HSV infection. However, adoptive transfer of HSV-sensitized spleen cells did provide significant protection against infection unless the spleen cells were treated with ATS prior to transfer. These experiments suggest that lymphocytes are involved in a cell-mediated response to subcutaneous HSV infection and demonstrate the importance of a noncompromised immune response in controlling spread of HSV from localized areas of infection."} {"id": "PMID:166927", "title": "Growth and cytopathology of Mycoplasma synoviae in chicken embryo cell cultures.", "content": "Mycoplasma synoviae was tested for its ability to grow and induce cytopathogenic changes in chicken embryo cell cultures. M. synoviae grew to high titers by day 5 in the presence of chick cells, but showed no growth in the tissue culture medium alone even though it was enriched with nicotinamide adenine dinucleotide and swine serum. Infected chick cell cultures showed a progressive cytoplasmic degeneration on successive days of examination. Early changes involved cytoplasmic granularity and mild vacuolation. On the last day of examination the cytoplasm of most cells was completely degenerated and some showed nuclear degeneration. M. synoviae was shown to be cytophilic for the chick cell membranes where the mycoplasmas reproduced and formed microcolonies which, on successive days, increased in size. The attachment site on the chick cell membrane was shown to be neuraminidase sensitive.", "contents": "Growth and cytopathology of Mycoplasma synoviae in chicken embryo cell cultures. Mycoplasma synoviae was tested for its ability to grow and induce cytopathogenic changes in chicken embryo cell cultures. M. synoviae grew to high titers by day 5 in the presence of chick cells, but showed no growth in the tissue culture medium alone even though it was enriched with nicotinamide adenine dinucleotide and swine serum. Infected chick cell cultures showed a progressive cytoplasmic degeneration on successive days of examination. Early changes involved cytoplasmic granularity and mild vacuolation. On the last day of examination the cytoplasm of most cells was completely degenerated and some showed nuclear degeneration. M. synoviae was shown to be cytophilic for the chick cell membranes where the mycoplasmas reproduced and formed microcolonies which, on successive days, increased in size. The attachment site on the chick cell membrane was shown to be neuraminidase sensitive."} {"id": "PMID:166928", "title": "Factors in the inactivation of Encephalomyocarditis virus in aerosols.", "content": "Encephalomyocarditis virus in aerosols is inactivated rapidly at relative humidities below 50%. In glycerol-water mixtures a similar decrease of infectivity occurs when the glycerol concentration exceeds 78% (wt/wt), corresponding to a relative humidity of 50%. The decay in aerosols does not involve oxygen or surface-dependent factors. Variation of temperature shows the inactivation to be a low-energy process with an activation enthalpy of 15 kcal per mol. The damage could be ascribed to dehydration of the virion, presumably proceeding to removal of structurally essential water molecules. This might trigger irreversible changes in the protein coat, resulting in disintegration of the virion.", "contents": "Factors in the inactivation of Encephalomyocarditis virus in aerosols. Encephalomyocarditis virus in aerosols is inactivated rapidly at relative humidities below 50%. In glycerol-water mixtures a similar decrease of infectivity occurs when the glycerol concentration exceeds 78% (wt/wt), corresponding to a relative humidity of 50%. The decay in aerosols does not involve oxygen or surface-dependent factors. Variation of temperature shows the inactivation to be a low-energy process with an activation enthalpy of 15 kcal per mol. The damage could be ascribed to dehydration of the virion, presumably proceeding to removal of structurally essential water molecules. This might trigger irreversible changes in the protein coat, resulting in disintegration of the virion."} {"id": "PMID:166929", "title": "Failure of attenuated temperature-sensitive influenza A (H3N2) virus to induce heterologous interference in humans to parainfluenza type 1 virus.", "content": "The present investigation was undertaken to determine if a candidate live vaccine virus, influenza A/Hong Kong/68-ts-1 [E] (H3N2), induced heterologous interference against an interferon-sensitive, wild-type, parainfluenza type 1 challenge virus. The parainfluenza virus was administered 7 days after Hong Kong/68-ts-1 [E] virus infection. The clinical response, daily quantitative virus shedding, interferon production, and serum and nasal wash antibody responses were determined in an experimental group (influenza A virus followed by parainfluenza virus) and 10 volunteers in a control group (parainfluenza virus only). The volunteers were selected on the basis of susceptibility to the two viruses, i.e. serum hemagglutination-inhibition antibody titer of is less than or greater to 1:8 for influenza virus and low nasal wash antibody titer (is less than or greater to 1:8) for parainfluenza virus. Despite a 100% infection rate in the Hong Kong/68-ts-1 [E] vaccinees, no heterologous interference was induced against the parainfluenza type 1 virus challenge.", "contents": "Failure of attenuated temperature-sensitive influenza A (H3N2) virus to induce heterologous interference in humans to parainfluenza type 1 virus. The present investigation was undertaken to determine if a candidate live vaccine virus, influenza A/Hong Kong/68-ts-1 [E] (H3N2), induced heterologous interference against an interferon-sensitive, wild-type, parainfluenza type 1 challenge virus. The parainfluenza virus was administered 7 days after Hong Kong/68-ts-1 [E] virus infection. The clinical response, daily quantitative virus shedding, interferon production, and serum and nasal wash antibody responses were determined in an experimental group (influenza A virus followed by parainfluenza virus) and 10 volunteers in a control group (parainfluenza virus only). The volunteers were selected on the basis of susceptibility to the two viruses, i.e. serum hemagglutination-inhibition antibody titer of is less than or greater to 1:8 for influenza virus and low nasal wash antibody titer (is less than or greater to 1:8) for parainfluenza virus. Despite a 100% infection rate in the Hong Kong/68-ts-1 [E] vaccinees, no heterologous interference was induced against the parainfluenza type 1 virus challenge."} {"id": "PMID:166930", "title": "Depressed specific cell-mediated immunity to Herpes simplex virus type 1 in patients with recurrent herpes labialis.", "content": "Cell-mediated immunity to herpes simplex virus type 1 (HSV-1) was assessed by a lymphocytotoxicity 51-Cr-release microassay procedure, using the MA-160 human prostatic adenoma cell line chronically infected with HSV-1 and its parent cell line as control. The specific immune release mean plus or minus standard deviation for nine asymptomatic patients with recurrent HSV-1 infections was 13.7 plus or minus 8.1%, compared to 28.9 plus or minus 8.4% in seven normal seropositive controls (P is less than 0.01). In four additional patients studied serially, the cell-mediated immunity was significantly increased during the recrudescence of herpetic infection, with a mean specific immune release value of 51.7 plus or minus 27.8%, compared to 8.7 plus or minus 1.5% during the convalescent period 2 to 10 weeks later (P is less than 0.05). These findings suggest that patients with recurrent HSV-1 infections have vigorous cellular immune responses during the acute phase but a specific impairment of cell-mediated immunity during the quiescent period, which may in part account for their susceptibility to recurrent herpetic infections.", "contents": "Depressed specific cell-mediated immunity to Herpes simplex virus type 1 in patients with recurrent herpes labialis. Cell-mediated immunity to herpes simplex virus type 1 (HSV-1) was assessed by a lymphocytotoxicity 51-Cr-release microassay procedure, using the MA-160 human prostatic adenoma cell line chronically infected with HSV-1 and its parent cell line as control. The specific immune release mean plus or minus standard deviation for nine asymptomatic patients with recurrent HSV-1 infections was 13.7 plus or minus 8.1%, compared to 28.9 plus or minus 8.4% in seven normal seropositive controls (P is less than 0.01). In four additional patients studied serially, the cell-mediated immunity was significantly increased during the recrudescence of herpetic infection, with a mean specific immune release value of 51.7 plus or minus 27.8%, compared to 8.7 plus or minus 1.5% during the convalescent period 2 to 10 weeks later (P is less than 0.05). These findings suggest that patients with recurrent HSV-1 infections have vigorous cellular immune responses during the acute phase but a specific impairment of cell-mediated immunity during the quiescent period, which may in part account for their susceptibility to recurrent herpetic infections."} {"id": "PMID:166933", "title": "The occurrence of tumours in F1, F2 and F3 descendants of bd rats exposed to N-nitrosomethylurea during pregnancy.", "content": "N-nitrosomethylurea (NMU) was administered once IP at a dose of 20 mg/kg to BD female rats on the 18th day of pregnancy. The first generation descendants (F1) were mated to produce a second generation (F2), which were then mated to produce a third generation (F3). While F1 rats were exposed directly to NMU during intrauterine life, it can be reasonably excluded that F2 and F3 descendants were exposed to NMU or its metabolites. F2 and F3 rats received no other treatment and untreated rats served as controls. Kidney and nervous-tissue tumours were observed in F1 descendants and, with a lower incidence, in F2 descendants. In F3 rats, tumours of nervous tissue, but not of kidneys, were observed. These results confirm previous observations that exposure to a carcinogen during prenatal life results in an increased cancer risk which may persist for more than one generation.", "contents": "The occurrence of tumours in F1, F2 and F3 descendants of bd rats exposed to N-nitrosomethylurea during pregnancy. N-nitrosomethylurea (NMU) was administered once IP at a dose of 20 mg/kg to BD female rats on the 18th day of pregnancy. The first generation descendants (F1) were mated to produce a second generation (F2), which were then mated to produce a third generation (F3). While F1 rats were exposed directly to NMU during intrauterine life, it can be reasonably excluded that F2 and F3 descendants were exposed to NMU or its metabolites. F2 and F3 rats received no other treatment and untreated rats served as controls. Kidney and nervous-tissue tumours were observed in F1 descendants and, with a lower incidence, in F2 descendants. In F3 rats, tumours of nervous tissue, but not of kidneys, were observed. These results confirm previous observations that exposure to a carcinogen during prenatal life results in an increased cancer risk which may persist for more than one generation."} {"id": "PMID:166934", "title": "Effect of cordycepin on the replication of type-c RNA tumor viruses.", "content": "Cordycepin (3'-deoxyadenosine) was previously shown to inhibit virus production induced by iododeoxyuridine from murine fibroblasts (Wu et al., 1972). We now report that the inhibitory effect of cordycepin results in a reduction of the number of cells producing virus as measured by the infectious center assay and fluorescent antibody technique. Cordycepin has a much greater inhibitory effect on viral replication than on transformation of normal rat kidney cells by murine sarcoma virus since viral production was greatly reduced (seven- to 35-fold) with 5-10 mug/ml of cordycepin while viral transformation was only slightly inhibited (two-fold reduction in focus-forming units) with the same concentration of cordycepin. Inhibition of viral production is most effective if the compound is present during the first 24 h after injection.", "contents": "Effect of cordycepin on the replication of type-c RNA tumor viruses. Cordycepin (3'-deoxyadenosine) was previously shown to inhibit virus production induced by iododeoxyuridine from murine fibroblasts (Wu et al., 1972). We now report that the inhibitory effect of cordycepin results in a reduction of the number of cells producing virus as measured by the infectious center assay and fluorescent antibody technique. Cordycepin has a much greater inhibitory effect on viral replication than on transformation of normal rat kidney cells by murine sarcoma virus since viral production was greatly reduced (seven- to 35-fold) with 5-10 mug/ml of cordycepin while viral transformation was only slightly inhibited (two-fold reduction in focus-forming units) with the same concentration of cordycepin. Inhibition of viral production is most effective if the compound is present during the first 24 h after injection."} {"id": "PMID:166935", "title": "Activation of C-type viruses during skin graft rejection in the mouse. Interrelationships between immunostimulation and immunosuppression.", "content": "Both mouse-tropic and zenotropic C-type RNA viruses were activated in BALB/c mice during rejection reactions against skin grafts from mice differing at the major histocompatibility locus (A/J) or sharing this locus (DBA/2). Animals that maintained their skin grafts following immunosuppression with antilymphocyte serum (ALS) or cyclophosphamide had a much higher incidence of virus-positivity than animals that did not receive ALS or cyclophosphamide, or that rejected their skin grafts despite immunosuppressive therapy. ALS itself activated type-C viruses from a small proportion of BALB/c mice whereas cyclophoshamide alone did not. Type C viruses were detected in spleens and regional nodes draining skin-graft sites between 1 and 2 weeks following transplantation; thereafter they reached maximum titers in spleens. Viruses were not detected at skin-graft sites, in tails or in thymuses of grafted animals. Virus activation was associated with splenic histological changes consisting of germinal center formation, diffuse hyperplasia of reticulum cells, depletion of periarteriolar lymphocytes and hyperplasia of red pulp hematopoietic elements.", "contents": "Activation of C-type viruses during skin graft rejection in the mouse. Interrelationships between immunostimulation and immunosuppression. Both mouse-tropic and zenotropic C-type RNA viruses were activated in BALB/c mice during rejection reactions against skin grafts from mice differing at the major histocompatibility locus (A/J) or sharing this locus (DBA/2). Animals that maintained their skin grafts following immunosuppression with antilymphocyte serum (ALS) or cyclophosphamide had a much higher incidence of virus-positivity than animals that did not receive ALS or cyclophosphamide, or that rejected their skin grafts despite immunosuppressive therapy. ALS itself activated type-C viruses from a small proportion of BALB/c mice whereas cyclophoshamide alone did not. Type C viruses were detected in spleens and regional nodes draining skin-graft sites between 1 and 2 weeks following transplantation; thereafter they reached maximum titers in spleens. Viruses were not detected at skin-graft sites, in tails or in thymuses of grafted animals. Virus activation was associated with splenic histological changes consisting of germinal center formation, diffuse hyperplasia of reticulum cells, depletion of periarteriolar lymphocytes and hyperplasia of red pulp hematopoietic elements."} {"id": "PMID:166936", "title": "EB Virus-associated nuclear antigen production and cell proliferation in adult peripheral blood leukocytes inoculated with the QIMR-WIL strain of EB virus.", "content": "A nuclear antigen, apparently the Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA), was detected by anticomplement immunofluorescence (ACIF) tests in adult peripheral blood leukocytes infected with the QIMR-WIL strain of EBV. EBNA was not detectable at 24 h but appeared in about 11% of the cells by 3 days, and by 5 days up to 64% of the cells were positive. Proliferation of EBNA-positive cells at this stage was confirmed by autoradiography. There was a good correlation between the concentration of virus and the number of EBNA-positive cells in the first 5-7 days. The subsequent course of events was found to be influenced by the initial cell concentration and the time of subculture. EBNA production was delayed in cells infected with higher dilutions of virus but subsequently appeared in a high proportion of cells. Indirect immunofluorescence failed to detect viral capsid antigen (VCA) or early antigen (EA) by 10 days. The results show that EBV infection was abortive and that the critical events of viral transformation occurred within the first few days.", "contents": "EB Virus-associated nuclear antigen production and cell proliferation in adult peripheral blood leukocytes inoculated with the QIMR-WIL strain of EB virus. A nuclear antigen, apparently the Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA), was detected by anticomplement immunofluorescence (ACIF) tests in adult peripheral blood leukocytes infected with the QIMR-WIL strain of EBV. EBNA was not detectable at 24 h but appeared in about 11% of the cells by 3 days, and by 5 days up to 64% of the cells were positive. Proliferation of EBNA-positive cells at this stage was confirmed by autoradiography. There was a good correlation between the concentration of virus and the number of EBNA-positive cells in the first 5-7 days. The subsequent course of events was found to be influenced by the initial cell concentration and the time of subculture. EBNA production was delayed in cells infected with higher dilutions of virus but subsequently appeared in a high proportion of cells. Indirect immunofluorescence failed to detect viral capsid antigen (VCA) or early antigen (EA) by 10 days. The results show that EBV infection was abortive and that the critical events of viral transformation occurred within the first few days."} {"id": "PMID:166937", "title": "Tumor-specific and forssman antigens of guinea-pig hepatoma cells: comparison of tumor cells grown in vivo and in vitro.", "content": "Cloned tumor-cell lines were derived from two antigenically distinct ascites variants of diethylnitrosamine-induced guinea-pig hepatomas (designated line 1 and line 10). Cell-surface antigens on the ascites and in vitro-grown tumor cells were analyzed with immunofluorescence, C1 fixation and transfer, and antibody-complement-mediated cytotoxity tests. Tumor-specific and Forssman antigens continued to be expressed during 3-6 months in vitro cultivation. Differences between ascites and cultured cells were noted in the degree of antigen expression and sensitivity to antibody-complement-mediated cytotoxicity. Cells grown in vitro exhibited a greater number of Forssman and tumor-specific antigen sites than in vivo grown cells as determined by the quantitative C1 fixation and transfer test. Immunofluorescent staining indicated that some cloned lines were considerably more homogeneous in terms of antigen expression than were the cultured, non-cloned parent cells or ascites-grown cells. Cloned lines were frequently more sensitive to the cytotoxic action of antibody and complement than were the in vivo grown and cultured non-cloned parent tumor cells. Sensitivity to cytotoxicity did not necessarily correlate, however, with the degree of antigen expression. These results suggest that; (1) the expression of Forssman and tumor-specific antigens does not diminish on cells cultivated in vitro and (2) ascites hepatoma cells in vivo are a heterogeneous population of cells differing in their degree of antigen expression and sensitivity to antibody-complement-mediated cytotoxicity.", "contents": "Tumor-specific and forssman antigens of guinea-pig hepatoma cells: comparison of tumor cells grown in vivo and in vitro. Cloned tumor-cell lines were derived from two antigenically distinct ascites variants of diethylnitrosamine-induced guinea-pig hepatomas (designated line 1 and line 10). Cell-surface antigens on the ascites and in vitro-grown tumor cells were analyzed with immunofluorescence, C1 fixation and transfer, and antibody-complement-mediated cytotoxity tests. Tumor-specific and Forssman antigens continued to be expressed during 3-6 months in vitro cultivation. Differences between ascites and cultured cells were noted in the degree of antigen expression and sensitivity to antibody-complement-mediated cytotoxicity. Cells grown in vitro exhibited a greater number of Forssman and tumor-specific antigen sites than in vivo grown cells as determined by the quantitative C1 fixation and transfer test. Immunofluorescent staining indicated that some cloned lines were considerably more homogeneous in terms of antigen expression than were the cultured, non-cloned parent cells or ascites-grown cells. Cloned lines were frequently more sensitive to the cytotoxic action of antibody and complement than were the in vivo grown and cultured non-cloned parent tumor cells. Sensitivity to cytotoxicity did not necessarily correlate, however, with the degree of antigen expression. These results suggest that; (1) the expression of Forssman and tumor-specific antigens does not diminish on cells cultivated in vitro and (2) ascites hepatoma cells in vivo are a heterogeneous population of cells differing in their degree of antigen expression and sensitivity to antibody-complement-mediated cytotoxicity."} {"id": "PMID:166938", "title": "Helper specificity for retrieval of defective friend virus.", "content": "A Friend virus-induced reticulum-cell sarcoma from BALB/c mice has been cultivated in vitro in our laboratory for more than 11 years and contains no detectable evidence of virus. However, Friend virus could be retrieved readily from the tissue cultures by any of several lymphatic leukemia viruses belonging to the Friend-Moloney-Rauscher (FMR) group, as long as the helper viruses were actively replicating in a culture. Helper activity appeared to be highly specific and limited to the FMR group including the B-tropic Tennant leukemia virus which produced a B-tropic Friend virus pseudotype. The naturally occurring type AKR murine leukemia viruses and the related Gross passage A virus failed both in vivo and in vitro to retrieve the Friend virus genome from the virus-free tumor cells.", "contents": "Helper specificity for retrieval of defective friend virus. A Friend virus-induced reticulum-cell sarcoma from BALB/c mice has been cultivated in vitro in our laboratory for more than 11 years and contains no detectable evidence of virus. However, Friend virus could be retrieved readily from the tissue cultures by any of several lymphatic leukemia viruses belonging to the Friend-Moloney-Rauscher (FMR) group, as long as the helper viruses were actively replicating in a culture. Helper activity appeared to be highly specific and limited to the FMR group including the B-tropic Tennant leukemia virus which produced a B-tropic Friend virus pseudotype. The naturally occurring type AKR murine leukemia viruses and the related Gross passage A virus failed both in vivo and in vitro to retrieve the Friend virus genome from the virus-free tumor cells."} {"id": "PMID:166939", "title": "The detection of the Epstein-Barr virus (EBV) nuclear antigen (EBNA) by anticomplement immunofluorescence. Immunoglobulin class of antibodies and role of complement.", "content": "The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was detected by anti-complement immunofluorescence (ACIF) in Raji lymphoblastoid cell line, and the mechanism of the reaction explored, using Ig fractions of anti-EBNA sera and purified components of complement. Following fractionation of serum from 13 donors, anti-EBNA antibodies were always found to be associated with IgG, but were also detectable in the IgM fraction of four sera. Sequential addition of functionally pure complement components in the ACIF reaction showed that the classical sequence of complement activation in involved. Anti-EBNA antibody reactions in Raji cell nuclei can also be detected by anti-Ig immunofluorescence with a low level of sensitivity. The same pattern of granular fluorescence was observed when C3 (beta1A/beta1C), or C4 or IgG anti-EBNA antibodies were revealed with the corresponding flurescein-conjugated reagents. Blocking of the ACIF reaction was achieved with Fab 2 anti-EBNA antibody fragments, which therefore provided an appropriate specificity control for the detection of EBNA.", "contents": "The detection of the Epstein-Barr virus (EBV) nuclear antigen (EBNA) by anticomplement immunofluorescence. Immunoglobulin class of antibodies and role of complement. The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was detected by anti-complement immunofluorescence (ACIF) in Raji lymphoblastoid cell line, and the mechanism of the reaction explored, using Ig fractions of anti-EBNA sera and purified components of complement. Following fractionation of serum from 13 donors, anti-EBNA antibodies were always found to be associated with IgG, but were also detectable in the IgM fraction of four sera. Sequential addition of functionally pure complement components in the ACIF reaction showed that the classical sequence of complement activation in involved. Anti-EBNA antibody reactions in Raji cell nuclei can also be detected by anti-Ig immunofluorescence with a low level of sensitivity. The same pattern of granular fluorescence was observed when C3 (beta1A/beta1C), or C4 or IgG anti-EBNA antibodies were revealed with the corresponding flurescein-conjugated reagents. Blocking of the ACIF reaction was achieved with Fab 2 anti-EBNA antibody fragments, which therefore provided an appropriate specificity control for the detection of EBNA."} {"id": "PMID:166940", "title": "Expression of SV40 T antigen during the cell cycle of sv40-transformed cells.", "content": "The expression of the nuclear SV40-induced T antigen was measured by microfluorimetry on individual, asynchronously growing SV40-transformed cells which had been stained with hamster T-antiserum by the indirect immunofluorescence method. The same individual cells were first measured for T antigen and then for DNA by Feulgen microspectrophotometry. A linear correlation was observed between the two parameters. T antigen expression was also measured in cell populations arrested at different phases of the cell cycle. Results of both types of experiments show that the expression of the gene (s) for T antigen in transformed cells increases during DNA replication and reaches its highest level in G2 nuclei. During mitosis T antigen is found in the cytoplasm.", "contents": "Expression of SV40 T antigen during the cell cycle of sv40-transformed cells. The expression of the nuclear SV40-induced T antigen was measured by microfluorimetry on individual, asynchronously growing SV40-transformed cells which had been stained with hamster T-antiserum by the indirect immunofluorescence method. The same individual cells were first measured for T antigen and then for DNA by Feulgen microspectrophotometry. A linear correlation was observed between the two parameters. T antigen expression was also measured in cell populations arrested at different phases of the cell cycle. Results of both types of experiments show that the expression of the gene (s) for T antigen in transformed cells increases during DNA replication and reaches its highest level in G2 nuclei. During mitosis T antigen is found in the cytoplasm."} {"id": "PMID:166941", "title": "Immunofluorescence and anti-complement immunofluorescence absorption tests for quantitation of Epstein-Barr virus-associated antigens.", "content": "Immunofluorescence absorption methods are described which permit quantitative estimation and differentiation of Epstein-Barr virus (EBV)-associated antigens (virus capsid antigen, VCA, early antigen, EA and EBV-determined nuclear antigen, EBNA) in cell extracts. EBNA was present in all cell lines (producer and non-producer) which carried the EBV-genome, while VCA and EA were present in producer lines only. All the antigens were absent from a lymphoid cell line (MOLT-4) which lacked the EBV-genome, as well as from leukemia cells from peripheral blood. The techniques demonstrated antigenic identity of the various antigens when prepared from different cell lines.", "contents": "Immunofluorescence and anti-complement immunofluorescence absorption tests for quantitation of Epstein-Barr virus-associated antigens. Immunofluorescence absorption methods are described which permit quantitative estimation and differentiation of Epstein-Barr virus (EBV)-associated antigens (virus capsid antigen, VCA, early antigen, EA and EBV-determined nuclear antigen, EBNA) in cell extracts. EBNA was present in all cell lines (producer and non-producer) which carried the EBV-genome, while VCA and EA were present in producer lines only. All the antigens were absent from a lymphoid cell line (MOLT-4) which lacked the EBV-genome, as well as from leukemia cells from peripheral blood. The techniques demonstrated antigenic identity of the various antigens when prepared from different cell lines."} {"id": "PMID:166942", "title": "Studies of Epstein-Barr virus (ebv)-associated nuclear antigen. I. assay in human lymphoblastoid cell lines by direct and indirect determination of 125I-IgG binding.", "content": "A quantitative assay for EBNA in human lymphoblastiod cell lines has been developed. The assay employs EBNA-positive and -negative 125-I-IgG preparations as reagents and can be used in a direct or indirect manner. EBNA specificity has been demonstrated in a number of ways. The antigenic relationship between EBNA present in Raji cells and in a number of other human lymphoblastiod cell lines of diverse origins and between the cell-associated antigen present in FT Raji cells and that present in isolated Raji nuclei has been studied. The possibility of carrying out blocking titrations for anti-EBNA determination has been demonstrated and the effect of glutaraldehyde and formaldehyde upon antigenic activity in FT Raji cells has been studied.", "contents": "Studies of Epstein-Barr virus (ebv)-associated nuclear antigen. I. assay in human lymphoblastoid cell lines by direct and indirect determination of 125I-IgG binding. A quantitative assay for EBNA in human lymphoblastiod cell lines has been developed. The assay employs EBNA-positive and -negative 125-I-IgG preparations as reagents and can be used in a direct or indirect manner. EBNA specificity has been demonstrated in a number of ways. The antigenic relationship between EBNA present in Raji cells and in a number of other human lymphoblastiod cell lines of diverse origins and between the cell-associated antigen present in FT Raji cells and that present in isolated Raji nuclei has been studied. The possibility of carrying out blocking titrations for anti-EBNA determination has been demonstrated and the effect of glutaraldehyde and formaldehyde upon antigenic activity in FT Raji cells has been studied."} {"id": "PMID:166943", "title": "Serum factors modifying cell mediated immunity to rat hepatoma d23 correlated with tumour growth.", "content": "Sera from rats bearing a progressively growing transplanted aminoazo-dye-induced hepatoma (hepatoma D23) have been examined for the presence of hepatoma D23-specfic antigen, antibody and immune complexes throughout the course of tumour growth. The levels of these factors have been correlated with the in vitro blocking and inhibition of cytotoxic lymph-node cells from immunized animals for cultured tumour cells. Sera from animals bearing small tumours (7-14 days after tumour implantation contain free tumour-specific antigen whilst immune complexes could not be detected. Although these sera were neither blocking nor inhibitory under the normal conditions of the test, when concentrated two and fourfold, inhibition but not blocking of lymph-node cell cytotoxicity could be detected. In comparison sera from animals bearing large tumours (24-28 days) blocked but did no inhibit in vitro lymph-node cell cytotoxicity and this correlates with the presence of tumour-specific immune complexes in antibody excess. Animals with intermediate-sized tumours had high levels of both blocking and inbibitory activity in the serum, these effects becoming apparent when neither free antibody nor free antigen could be detected. The relevance of these findings to the mechanism by which a growing tumour may escape specific cellular immune destruction is discussed.", "contents": "Serum factors modifying cell mediated immunity to rat hepatoma d23 correlated with tumour growth. Sera from rats bearing a progressively growing transplanted aminoazo-dye-induced hepatoma (hepatoma D23) have been examined for the presence of hepatoma D23-specfic antigen, antibody and immune complexes throughout the course of tumour growth. The levels of these factors have been correlated with the in vitro blocking and inhibition of cytotoxic lymph-node cells from immunized animals for cultured tumour cells. Sera from animals bearing small tumours (7-14 days after tumour implantation contain free tumour-specific antigen whilst immune complexes could not be detected. Although these sera were neither blocking nor inhibitory under the normal conditions of the test, when concentrated two and fourfold, inhibition but not blocking of lymph-node cell cytotoxicity could be detected. In comparison sera from animals bearing large tumours (24-28 days) blocked but did no inhibit in vitro lymph-node cell cytotoxicity and this correlates with the presence of tumour-specific immune complexes in antibody excess. Animals with intermediate-sized tumours had high levels of both blocking and inbibitory activity in the serum, these effects becoming apparent when neither free antibody nor free antigen could be detected. The relevance of these findings to the mechanism by which a growing tumour may escape specific cellular immune destruction is discussed."} {"id": "PMID:166944", "title": "Rat cell line 3y1 and its virogenic polyoma- and sv40- transformed derivatives.", "content": "Cell lines were established from cultures derived from Fischer rat embryos according to the transfer schedule described by Todaro and Green (1963) for mouse 3T3 cells where cell crowding and serum exhaustion were kept to a minimum. Cell growth rate did not decline greatly during the course of successive 3-day transfers. Like 3T3 cells the rat cell lines possess very low saturation desities under standard culture conditions. A clonal cell line with a relatively high plating efficiency as obtained from one of the cell lines, 3YL. In these cloned cultures, virus growth was not detectable upon infection with SV40, while a small amount of virus was produced upon infection with polyoma virus. Morphological transformation of the cloned 3Y1 cells by SV40 and polyoma virus could be assayed with single-hit kinetics and with effieiencies comparable to those of the previously available transformation systems for each virus. Independent cell lines transformed by SV40 were consistently virus-free and all the lines tested produced SV40 upon fusion with permissive monkey cells. Most of the independent transfromed cell lines isolated after polyoma infection appeared to be virus-free, although the cultures of some lines produced a small amount of polyoma virus spontaneously after a prolonged cultivation. Most of the virus-free polyoma-transformed lines produced virus upon fusion with permissive mouse cells.", "contents": "Rat cell line 3y1 and its virogenic polyoma- and sv40- transformed derivatives. Cell lines were established from cultures derived from Fischer rat embryos according to the transfer schedule described by Todaro and Green (1963) for mouse 3T3 cells where cell crowding and serum exhaustion were kept to a minimum. Cell growth rate did not decline greatly during the course of successive 3-day transfers. Like 3T3 cells the rat cell lines possess very low saturation desities under standard culture conditions. A clonal cell line with a relatively high plating efficiency as obtained from one of the cell lines, 3YL. In these cloned cultures, virus growth was not detectable upon infection with SV40, while a small amount of virus was produced upon infection with polyoma virus. Morphological transformation of the cloned 3Y1 cells by SV40 and polyoma virus could be assayed with single-hit kinetics and with effieiencies comparable to those of the previously available transformation systems for each virus. Independent cell lines transformed by SV40 were consistently virus-free and all the lines tested produced SV40 upon fusion with permissive monkey cells. Most of the independent transfromed cell lines isolated after polyoma infection appeared to be virus-free, although the cultures of some lines produced a small amount of polyoma virus spontaneously after a prolonged cultivation. Most of the virus-free polyoma-transformed lines produced virus upon fusion with permissive mouse cells."} {"id": "PMID:166945", "title": "Control of nuclear division in sv40 and adenovirus type 12 transformed mouse 3t3 cells.", "content": "Untransformed, non-tumorigenic mouse cells respond to cytochalasin B (CB) with limited nuclear division. BALB/c mouse embryo fibroblasts (MEF) and both BALB/c 3T3 and Swiss 3T3 cells become binucleated in the presence of CB and cells with three or more nuclei are very rare or undetectable. MEF are diploid (40 chromosomes) and 3T3 cells are subtetraploid (74-76 chromosomes). Transformation of MEF by SV40 produces a dramatic change in response to CB. These cells, which contain SV40 T-antigen, become highly multinucleated in the presence of CB. More than 20% of the cells have at least seven nuclei. Also premature chromosome condensation (PCC), an abnormality rare in CB-treated normal cells but one which is common to highly multinucleated cells, is frequent and occurs in at least 10% of mitoses. SV40-transformed MEF have 40 or 80 chromosomes, e.g. are diploid or tetraploid. Transformation of 3T3 by SV40 or adenovirus type 12 does not result in a marked change in the response to CB. Although some trinucleate and tetranucleate cells are formed, cells with more nuclei are undetectable or rare. PCC is also rare. These cells show chromosome numbers somewhat lower than their untransformed parents and in one line the chromosome number appears to decrease with passage of the cells. This failure to undergo a marked change in responsiveness to CB following transformation is not a characteristic of all transformed 3T3 cells. SVT2, a line of 3T3 which was transformed by SV40 prior to its establishment as a continuous line, responds to CB with a high degree of multinucleation. These cells are diploid. These results suggests that 3T3 cells are constitutive for controlled nuclear division and that this feature may be related to chromosome constitution.", "contents": "Control of nuclear division in sv40 and adenovirus type 12 transformed mouse 3t3 cells. Untransformed, non-tumorigenic mouse cells respond to cytochalasin B (CB) with limited nuclear division. BALB/c mouse embryo fibroblasts (MEF) and both BALB/c 3T3 and Swiss 3T3 cells become binucleated in the presence of CB and cells with three or more nuclei are very rare or undetectable. MEF are diploid (40 chromosomes) and 3T3 cells are subtetraploid (74-76 chromosomes). Transformation of MEF by SV40 produces a dramatic change in response to CB. These cells, which contain SV40 T-antigen, become highly multinucleated in the presence of CB. More than 20% of the cells have at least seven nuclei. Also premature chromosome condensation (PCC), an abnormality rare in CB-treated normal cells but one which is common to highly multinucleated cells, is frequent and occurs in at least 10% of mitoses. SV40-transformed MEF have 40 or 80 chromosomes, e.g. are diploid or tetraploid. Transformation of 3T3 by SV40 or adenovirus type 12 does not result in a marked change in the response to CB. Although some trinucleate and tetranucleate cells are formed, cells with more nuclei are undetectable or rare. PCC is also rare. These cells show chromosome numbers somewhat lower than their untransformed parents and in one line the chromosome number appears to decrease with passage of the cells. This failure to undergo a marked change in responsiveness to CB following transformation is not a characteristic of all transformed 3T3 cells. SVT2, a line of 3T3 which was transformed by SV40 prior to its establishment as a continuous line, responds to CB with a high degree of multinucleation. These cells are diploid. These results suggests that 3T3 cells are constitutive for controlled nuclear division and that this feature may be related to chromosome constitution."} {"id": "PMID:166946", "title": "Subpopulations of multiparous rat lymph-node cells cytotoxic for rat tumour cells and capable of suppressing cytotoxicity in vitro.", "content": "Lymph-node cells (LNC) from multiparous pregnant rats were separated on columns prepared from nylon wool, and tested for cytotoxicity against target tumour cells. Reactivity of LNC towards hepatoma D23 and mammary carcinoma AAF57 was demonstrated in cell populations retained on the nylon wool, and not with cells eluted from the column. Although only 25% of the samples of unfractionated LNC were cytotoxic for tumour cells, retained cell fractions were cytotoxic in 11 out of 12 tests (p = less than 0.05). Similarly retained LNC were also cytotoxic for 15-day-old embryo cells but not for normal adult rat fibroblasts. Using multiparous rat serum it was shown that the reactivity of the retained LNC population could be abrogated in eight out of 11 tests (p = less than 0.05). The LNC population recovered from the nylon wool constituted 28 to 35% of the original LNC preparation, and consisted of 60-70% Ig-bearing cells together with a subpopulation of cells responding to soluble PHA. Separation of multiparous LNC on glass beads coated with rat Ig and then rabbit anti-rat Ig (in excess) also demonstrated the retained cell population to be cytotoxic against tumour cells. Approximately 17-20% of the original cell population was recovered from cells retained on the column, and consisted of an enriched Ig-bearing cell population (65-80% Ig-bearing cells) and LNC responsive to PHA. Carbonyl iron treatment of multiparous rat LNC was found to remove detectable cytotoxicity from multiparous rat LNC preparations. The cytotoxicity of multiparous rat LNC retained on nylon wool was also abolished following incubation with carbonyl iron. Definite conclusions as to the nature of the effector cell cannot be drawn from this test, since carbonyl iron treatment was found to remove not only phagocytic cells from LNC preparations but also a proportion of other cell populations including Ig-bearing lymphocytes... In addition to detecting a cytotoxic LNC population reactive towards tumour-associated embryonic antigens (retained fractions from nylon-wool column separation), a subpopulation of multiparous rat LNC was demonstrated in cell fractions eluted from the nylon wool which was shown to suppress the cytotoxicity of the retained multiparous LNC population. The exact nature of this subpopulation of LNC and the mechanism of action is at present not known.", "contents": "Subpopulations of multiparous rat lymph-node cells cytotoxic for rat tumour cells and capable of suppressing cytotoxicity in vitro. Lymph-node cells (LNC) from multiparous pregnant rats were separated on columns prepared from nylon wool, and tested for cytotoxicity against target tumour cells. Reactivity of LNC towards hepatoma D23 and mammary carcinoma AAF57 was demonstrated in cell populations retained on the nylon wool, and not with cells eluted from the column. Although only 25% of the samples of unfractionated LNC were cytotoxic for tumour cells, retained cell fractions were cytotoxic in 11 out of 12 tests (p = less than 0.05). Similarly retained LNC were also cytotoxic for 15-day-old embryo cells but not for normal adult rat fibroblasts. Using multiparous rat serum it was shown that the reactivity of the retained LNC population could be abrogated in eight out of 11 tests (p = less than 0.05). The LNC population recovered from the nylon wool constituted 28 to 35% of the original LNC preparation, and consisted of 60-70% Ig-bearing cells together with a subpopulation of cells responding to soluble PHA. Separation of multiparous LNC on glass beads coated with rat Ig and then rabbit anti-rat Ig (in excess) also demonstrated the retained cell population to be cytotoxic against tumour cells. Approximately 17-20% of the original cell population was recovered from cells retained on the column, and consisted of an enriched Ig-bearing cell population (65-80% Ig-bearing cells) and LNC responsive to PHA. Carbonyl iron treatment of multiparous rat LNC was found to remove detectable cytotoxicity from multiparous rat LNC preparations. The cytotoxicity of multiparous rat LNC retained on nylon wool was also abolished following incubation with carbonyl iron. Definite conclusions as to the nature of the effector cell cannot be drawn from this test, since carbonyl iron treatment was found to remove not only phagocytic cells from LNC preparations but also a proportion of other cell populations including Ig-bearing lymphocytes... In addition to detecting a cytotoxic LNC population reactive towards tumour-associated embryonic antigens (retained fractions from nylon-wool column separation), a subpopulation of multiparous rat LNC was demonstrated in cell fractions eluted from the nylon wool which was shown to suppress the cytotoxicity of the retained multiparous LNC population. The exact nature of this subpopulation of LNC and the mechanism of action is at present not known."} {"id": "PMID:166947", "title": "Epidemiological studies on feline leukaemia virus infection. I. A serological survey in urban cats.", "content": "A survey of the incidence of feline leukaemia virus (FeLV) infection in cats in a large urban area was made by studying the prevalence of antibodies to feline leukaemia virus-associated cell membrane antigens. Two serological tests were used, immunofluorescence and a mixed immunoglobulin rosette technique. The overall incidence of cats with antibodies was 40%, contrasting with 6% in the surrounding rural area. Only 6% of urban kittens were positive while 50% of adults had antibodies. The incidence in adults rose from 29% at 5-6 months to 74% in cats over 3 years. Stray cats had an incidence twice as high as that of domestic pets. These results support and extend earlier findings that FeLV infection is common and is horizontally transmitted.", "contents": "Epidemiological studies on feline leukaemia virus infection. I. A serological survey in urban cats. A survey of the incidence of feline leukaemia virus (FeLV) infection in cats in a large urban area was made by studying the prevalence of antibodies to feline leukaemia virus-associated cell membrane antigens. Two serological tests were used, immunofluorescence and a mixed immunoglobulin rosette technique. The overall incidence of cats with antibodies was 40%, contrasting with 6% in the surrounding rural area. Only 6% of urban kittens were positive while 50% of adults had antibodies. The incidence in adults rose from 29% at 5-6 months to 74% in cats over 3 years. Stray cats had an incidence twice as high as that of domestic pets. These results support and extend earlier findings that FeLV infection is common and is horizontally transmitted."} {"id": "PMID:166948", "title": "Oncogenic transformation of primary hamster cells by herpes simplex virus type 2 (hsv-2) and an hsv-2 temperature-sensitive mutant.", "content": "Six oncogenically transformed cell lines were obtained following infection of hamster embryo fibroblasts with UV-irradiated herpes simplex virus type 2 (HSV-2) or with an HSV-2 temperature-sensitive mutant. All lines produced undifferentiated fibrosarcomas in newborn hamsters, four of the six lines produced metastatic tumors in the lung, and sera from tumor-bearing hamsters contained neutralizing antibody to HSV-2. HSV-specific cell-surface antigen (s) was detected by immunogluorescence tests in all six of the lines established from primary tumors. Antibody to an early, HSV-specific, non-structural polypeptide (VP134) reacted by immunofluorescence with antigen(s) in fixed preparation of three of the six tumor-cell lines.", "contents": "Oncogenic transformation of primary hamster cells by herpes simplex virus type 2 (hsv-2) and an hsv-2 temperature-sensitive mutant. Six oncogenically transformed cell lines were obtained following infection of hamster embryo fibroblasts with UV-irradiated herpes simplex virus type 2 (HSV-2) or with an HSV-2 temperature-sensitive mutant. All lines produced undifferentiated fibrosarcomas in newborn hamsters, four of the six lines produced metastatic tumors in the lung, and sera from tumor-bearing hamsters contained neutralizing antibody to HSV-2. HSV-specific cell-surface antigen (s) was detected by immunogluorescence tests in all six of the lines established from primary tumors. Antibody to an early, HSV-specific, non-structural polypeptide (VP134) reacted by immunofluorescence with antigen(s) in fixed preparation of three of the six tumor-cell lines."} {"id": "PMID:166949", "title": "Antibody patterns to herpesviruses in kaposi's sarcoma: serological association of european kaposi's sarcoma with cytomegalovirus.", "content": "Sera from patients with Kaposi's sarcoma (KS) were examined for antibody titres to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) types 1 and 2 by four techniques: indirect haemagglutination (IHA), complement fixation (CF), virus neutralization (NT) and indirect immunofluorescence (IF). The patients were classified, according to the stage of disease, as progressive and regressive. Control sera were obtained from healthy adults, matched for age, sex, race, socioeconomic status and geographic location, as well as from patients with melanoma, some of whom were receiving chemotherapy similar to that given to the KS patients. All KS sera contained CMV-neutralizing antibodies. Seventy-five percent of the European KS patients, mainly regressors, showed elevated anti-CMV titres by IHA with a significant increase in the geometric mean over the corresponding healthy adult group and the melanoma group. An overrepresentation of high anti-CMV titres, although less marked, was found by CF. There was no significant association with antibodies to EBV, HSV-1 and HSV-2 related antigens. By contrast, the African KS patients, mainly progressors, did not show a serologic association with CMV or with EBV and HSV-1 and 2. The implication of these results is discussed.", "contents": "Antibody patterns to herpesviruses in kaposi's sarcoma: serological association of european kaposi's sarcoma with cytomegalovirus. Sera from patients with Kaposi's sarcoma (KS) were examined for antibody titres to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) types 1 and 2 by four techniques: indirect haemagglutination (IHA), complement fixation (CF), virus neutralization (NT) and indirect immunofluorescence (IF). The patients were classified, according to the stage of disease, as progressive and regressive. Control sera were obtained from healthy adults, matched for age, sex, race, socioeconomic status and geographic location, as well as from patients with melanoma, some of whom were receiving chemotherapy similar to that given to the KS patients. All KS sera contained CMV-neutralizing antibodies. Seventy-five percent of the European KS patients, mainly regressors, showed elevated anti-CMV titres by IHA with a significant increase in the geometric mean over the corresponding healthy adult group and the melanoma group. An overrepresentation of high anti-CMV titres, although less marked, was found by CF. There was no significant association with antibodies to EBV, HSV-1 and HSV-2 related antigens. By contrast, the African KS patients, mainly progressors, did not show a serologic association with CMV or with EBV and HSV-1 and 2. The implication of these results is discussed."} {"id": "PMID:166950", "title": "Ion-selective electrodes and enzyme electrodes in environmental and clinical studies.", "content": "Electrodes have been developed for the assay of glucose, urea, amino acids, uric acid, phosphate, nitrate and perchlorate. The electrodes for the organic compounds are enzyme electrodes which are prepared by chemically immobilizing an enzyme over the outside of a conventional ion-selective electrode. These electrodes will be discussed in depth. The progress and the development of the electrodes that show sensitivity and selectivity for phosphate, nitrate and perchlorate will be outlined. The basis of these sensors is a complex of a transition metal of either an analog of thiourea or an organic chelator, such as 1,10-phenanthraline. Such electrodes respond linearly to phosphate, nitrate or perchlorate, and show selectivity over sulphate, halides and acetate. The linear range of all these electrodes is approx. 10(-1)-10(-5) M with a near Nernstian slope and a reproducibility of 1%. The electrodes are stable and can be used continuously.", "contents": "Ion-selective electrodes and enzyme electrodes in environmental and clinical studies. Electrodes have been developed for the assay of glucose, urea, amino acids, uric acid, phosphate, nitrate and perchlorate. The electrodes for the organic compounds are enzyme electrodes which are prepared by chemically immobilizing an enzyme over the outside of a conventional ion-selective electrode. These electrodes will be discussed in depth. The progress and the development of the electrodes that show sensitivity and selectivity for phosphate, nitrate and perchlorate will be outlined. The basis of these sensors is a complex of a transition metal of either an analog of thiourea or an organic chelator, such as 1,10-phenanthraline. Such electrodes respond linearly to phosphate, nitrate or perchlorate, and show selectivity over sulphate, halides and acetate. The linear range of all these electrodes is approx. 10(-1)-10(-5) M with a near Nernstian slope and a reproducibility of 1%. The electrodes are stable and can be used continuously."} {"id": "PMID:166953", "title": "Synergistic effects of fad and acth on the 32-p turnover in the adrenal of rats treated with a one shot administration of dexamethasone phosphate.", "content": "The effects of Flavin Adenine Dinucleotide (FAD) and of vitamin A for two days to 25 days old rats has been studied on liver of rats treated with a one shot administration of dexamethasone phosphate were investigated. Efforts were made to determine whether or not ACTH participates in the action of FAD which affects adrenal atrophy induced by steroid hormone administration. The large decrease in adrenals 32-P turnover in rat treated with a one shot administration of dexamethasone phosphate was reduced by intraperitoneal administration of FAD or ACTH alone. This tendency of reduced loss was further promoted by an administration of ACTH simultaneously with the FAD. These results suggest the presence of a new physiological role for FAD i.e. FAD is able to potentiate the action of ACTH. The role was discussed of a possible synergism between FAD and ACTH with regard to their action on the induction of adrenal atrophy by steroid administration.", "contents": "Synergistic effects of fad and acth on the 32-p turnover in the adrenal of rats treated with a one shot administration of dexamethasone phosphate. The effects of Flavin Adenine Dinucleotide (FAD) and of vitamin A for two days to 25 days old rats has been studied on liver of rats treated with a one shot administration of dexamethasone phosphate were investigated. Efforts were made to determine whether or not ACTH participates in the action of FAD which affects adrenal atrophy induced by steroid hormone administration. The large decrease in adrenals 32-P turnover in rat treated with a one shot administration of dexamethasone phosphate was reduced by intraperitoneal administration of FAD or ACTH alone. This tendency of reduced loss was further promoted by an administration of ACTH simultaneously with the FAD. These results suggest the presence of a new physiological role for FAD i.e. FAD is able to potentiate the action of ACTH. The role was discussed of a possible synergism between FAD and ACTH with regard to their action on the induction of adrenal atrophy by steroid administration."} {"id": "PMID:166958", "title": "Interference of pregnancy steroid hormones with FPN test for estimation of phenothiazine derivatives in urine.", "content": "Interference of pregnancy steroid hormones with FPN test for estimation of some phenothiazine derivatives in urine has been investigated. The FPN test was positive in 97.9% of urine samples obtained from pregnant women. It is supposed that metabolites of estrogens and progestagens present in higher amounts in urine samples of these women are responsible for this positivity.", "contents": "Interference of pregnancy steroid hormones with FPN test for estimation of phenothiazine derivatives in urine. Interference of pregnancy steroid hormones with FPN test for estimation of some phenothiazine derivatives in urine has been investigated. The FPN test was positive in 97.9% of urine samples obtained from pregnant women. It is supposed that metabolites of estrogens and progestagens present in higher amounts in urine samples of these women are responsible for this positivity."} {"id": "PMID:166959", "title": "Ongoing occipital rhythms and the VER. I. Stimulation at peaks of the alpha-rhythm.", "content": "As a first step toward determining the source of variability in the visually evoked response (VER) between subjects, we have examined the relationships between the VER and the alpha-rhythm. This was done by comparing the VER's to photic stimuli delivered at positive and negative peaks of the alpha-rhythm (alpha-synchronized stimuli) with VER's to flashes delivered at a fixed interval, unsynchronized with the alpha-rhythm. Average VER's for the three classes of stimuli were calcuated for each of ten subjects. In addition, a grand average VER (GVVER) WAS CALCULATED FOR EACH STIMULUS CLASS BY AVERAGING THE INDIVIDUAL AVERAGE VER's. Quantitative comparisons between GVER's were made using cross- correlograms. Cross-correlograms were calculated between each of the GVER's, and between the GVER's to alpha-synchronized stimulation and their controls. These data show that the first 120 msec. poststimulus interval of the Gver's to alpha-synchronized stimulation are highly correlated with the prestimulus alpha- rhythm. The data also show a component occurring in al GVER's which is independent of the alpha-rhythm. This component begins 120 msec. After stimulation, reaches peak amplitude at 200 msec, and decays to baseline at 240 msec. Thses findings suggest that much of the variability in VER recordings may be due to alpha-activity which has been insufficiently attenuated by averaging.", "contents": "Ongoing occipital rhythms and the VER. I. Stimulation at peaks of the alpha-rhythm. As a first step toward determining the source of variability in the visually evoked response (VER) between subjects, we have examined the relationships between the VER and the alpha-rhythm. This was done by comparing the VER's to photic stimuli delivered at positive and negative peaks of the alpha-rhythm (alpha-synchronized stimuli) with VER's to flashes delivered at a fixed interval, unsynchronized with the alpha-rhythm. Average VER's for the three classes of stimuli were calcuated for each of ten subjects. In addition, a grand average VER (GVVER) WAS CALCULATED FOR EACH STIMULUS CLASS BY AVERAGING THE INDIVIDUAL AVERAGE VER's. Quantitative comparisons between GVER's were made using cross- correlograms. Cross-correlograms were calculated between each of the GVER's, and between the GVER's to alpha-synchronized stimulation and their controls. These data show that the first 120 msec. poststimulus interval of the Gver's to alpha-synchronized stimulation are highly correlated with the prestimulus alpha- rhythm. The data also show a component occurring in al GVER's which is independent of the alpha-rhythm. This component begins 120 msec. After stimulation, reaches peak amplitude at 200 msec, and decays to baseline at 240 msec. Thses findings suggest that much of the variability in VER recordings may be due to alpha-activity which has been insufficiently attenuated by averaging."} {"id": "PMID:166960", "title": "Growth of calcium oxalate crystals. II. Inhibition by natural urinary crystal growth inhibitors.", "content": "A method is described for quantitatively determining the inhibitory activity of pure components, isolates, or mixtures of components (such as urine) on the growth of calcium oxalate crystals. Results with known calcium phosphate crystal growth inhibitors--magnesium, citrate, and pyrophosphate--suggest that these components contribute little to the ability to normal urine to inhibit the growth of calcium oxalate crystals. As yet unidentified urinary components seem to be responsible for most of this activity. The urinary crystal growth inhibitors appear to function by adsorbing on the surface of the growing crystals, thereby preventing the further incorporation of lattice ions. The fit of experimental data to the Langmuir absorption isotherm supports this conclusion.", "contents": "Growth of calcium oxalate crystals. II. Inhibition by natural urinary crystal growth inhibitors. A method is described for quantitatively determining the inhibitory activity of pure components, isolates, or mixtures of components (such as urine) on the growth of calcium oxalate crystals. Results with known calcium phosphate crystal growth inhibitors--magnesium, citrate, and pyrophosphate--suggest that these components contribute little to the ability to normal urine to inhibit the growth of calcium oxalate crystals. As yet unidentified urinary components seem to be responsible for most of this activity. The urinary crystal growth inhibitors appear to function by adsorbing on the surface of the growing crystals, thereby preventing the further incorporation of lattice ions. The fit of experimental data to the Langmuir absorption isotherm supports this conclusion."} {"id": "PMID:166961", "title": "Pathogenesis of pyelonephritis. Escherichia coli-induced renal ultrastructural changes.", "content": "Escherichia coli-induced renal ultrastructural changes were observed 4 hr after the intravenous injection of 2 times 10-minus 6 bacteria. The initial changes consisted of mitochondrial swelling followed by intracellular vacuolation, nuclear membrane dilation, and increased lysosomal phagocytic activity. Alterations in the appearance of proximal tubular lysosomes included a loss of osmiophilic staining properties. Many of the involved cells showed necrosis and can presumably act as a nidus for bacterial proliferation.", "contents": "Pathogenesis of pyelonephritis. Escherichia coli-induced renal ultrastructural changes. Escherichia coli-induced renal ultrastructural changes were observed 4 hr after the intravenous injection of 2 times 10-minus 6 bacteria. The initial changes consisted of mitochondrial swelling followed by intracellular vacuolation, nuclear membrane dilation, and increased lysosomal phagocytic activity. Alterations in the appearance of proximal tubular lysosomes included a loss of osmiophilic staining properties. Many of the involved cells showed necrosis and can presumably act as a nidus for bacterial proliferation."} {"id": "PMID:166965", "title": "A new fluorescent method for the demonstration of macromolecular aldehydes.", "content": "The fluorochrome, p-hydrazinoacridine (HA), is used to stain selectively natural macromolecular aldehydes as occur in elastic tissue as well as periodic acid (oxidized) or hydrochloric acid (hydrolyzed) engendered polyaldehydes (e.g., respectively of glycogen, mucosubstances and deoxyribonucleic acid). The reaction is independent of SO2 required in Schiff-type reactions. The mechanism of the staining reaction is presumably via the formation of fluorescent hydrazones from aldehyde condensation with HA. Aldehyde blocking agents, i.e., thiosemicarbazide and sodium borohydride, block the staining reactions with HA. In view of the controversy surrounding the mechanism of Schiff-type reactions and the lack of an adequate explanation for the affinity of miscellaneous fluorochromes for elastic tissue, p-hydrazinoacridine appears to be an ideal reagent, combining a simple staining procedure, excellent histological results and a straightforward mechanism for its selectivity.", "contents": "A new fluorescent method for the demonstration of macromolecular aldehydes. The fluorochrome, p-hydrazinoacridine (HA), is used to stain selectively natural macromolecular aldehydes as occur in elastic tissue as well as periodic acid (oxidized) or hydrochloric acid (hydrolyzed) engendered polyaldehydes (e.g., respectively of glycogen, mucosubstances and deoxyribonucleic acid). The reaction is independent of SO2 required in Schiff-type reactions. The mechanism of the staining reaction is presumably via the formation of fluorescent hydrazones from aldehyde condensation with HA. Aldehyde blocking agents, i.e., thiosemicarbazide and sodium borohydride, block the staining reactions with HA. In view of the controversy surrounding the mechanism of Schiff-type reactions and the lack of an adequate explanation for the affinity of miscellaneous fluorochromes for elastic tissue, p-hydrazinoacridine appears to be an ideal reagent, combining a simple staining procedure, excellent histological results and a straightforward mechanism for its selectivity."} {"id": "PMID:166966", "title": "Ultrastructural demonstration of NAD-pyrophosphorylase activity in mouse liver nuclei.", "content": "Ultrastructural demonstration of NAD-pyrophosphorylase activity (E.C.2.7.7.1) in isolated mouse liver nuclei was investigated with the use of an electronhistochemical procedure based on the precipitation of pyrophosphate ions with lead ions under conditions permitting simultaneous ATPase inhibition by formaldehyde/ethanol prefixation. In isolated mouse liver nuclei activity of NAD-pyrophosphorylase was found in nucleoli, in interchromatin granules, coiled bodies and strand-like structures in nucleoplasm.", "contents": "Ultrastructural demonstration of NAD-pyrophosphorylase activity in mouse liver nuclei. Ultrastructural demonstration of NAD-pyrophosphorylase activity (E.C.2.7.7.1) in isolated mouse liver nuclei was investigated with the use of an electronhistochemical procedure based on the precipitation of pyrophosphate ions with lead ions under conditions permitting simultaneous ATPase inhibition by formaldehyde/ethanol prefixation. In isolated mouse liver nuclei activity of NAD-pyrophosphorylase was found in nucleoli, in interchromatin granules, coiled bodies and strand-like structures in nucleoplasm."} {"id": "PMID:166967", "title": "Ultrastructural demonstration of phosphatases by perfusion fixation followed by perfusion incubation of rat liver.", "content": "An alternative to previous methods (tissue chopper, frozen sections) for the ultrastructural demonstration of phosphatases is described. The present approach is based on a short vascular perfusion of rat liver with glutaraldehyde through the inferior caval vein, followed by vascular perfusion incubation with a medium containing the enzyme substrates. The effect of glutaraldehyde on three different types of phosphatases was investigated, namely a lysosomal enzyme (acid phosphatase) a tightly bound microsomal enzyme (G6Pase) and a loosely bound microsomal enzyme (IDPase). It is demonstrated that by perfusion with glutaraldehyde for three minutes good cellular morphology is obtained and that 50-60% of the initial activity of glucose-6-phosphatase, inosine-diphosphatase and acid phosphatase remains. The localization and deposition of G6Pase activity were distinct and observed throughout the endoplasmic reticulum and the nuclear envelope. For acid phosphatase, the reaction product was confined to various types of lysosomes including presumed autophagic vacuoles. No signs of enzyme diffusion were noted. The present approach seems to offer some advantages: it is simple and requires no extra equipment, penetration of the fixative and incubation enzyme medium is good, and finally freeze artifacts are avoided.", "contents": "Ultrastructural demonstration of phosphatases by perfusion fixation followed by perfusion incubation of rat liver. An alternative to previous methods (tissue chopper, frozen sections) for the ultrastructural demonstration of phosphatases is described. The present approach is based on a short vascular perfusion of rat liver with glutaraldehyde through the inferior caval vein, followed by vascular perfusion incubation with a medium containing the enzyme substrates. The effect of glutaraldehyde on three different types of phosphatases was investigated, namely a lysosomal enzyme (acid phosphatase) a tightly bound microsomal enzyme (G6Pase) and a loosely bound microsomal enzyme (IDPase). It is demonstrated that by perfusion with glutaraldehyde for three minutes good cellular morphology is obtained and that 50-60% of the initial activity of glucose-6-phosphatase, inosine-diphosphatase and acid phosphatase remains. The localization and deposition of G6Pase activity were distinct and observed throughout the endoplasmic reticulum and the nuclear envelope. For acid phosphatase, the reaction product was confined to various types of lysosomes including presumed autophagic vacuoles. No signs of enzyme diffusion were noted. The present approach seems to offer some advantages: it is simple and requires no extra equipment, penetration of the fixative and incubation enzyme medium is good, and finally freeze artifacts are avoided."} {"id": "PMID:166968", "title": "Ultrastructural localization of glucose 6-phosphatase activity in tracheal epithelium of the rat.", "content": "Ultrastructural localization of glucose 6-phosphatase activity was studied in the tracheal epithelium of the rat. The reaction product for the enzyme activity was localized in the endoplasmic reticulum and nuclear envelope of all cell types composing the tracheal epithelium, namely ciliated cells, goblet cells, brush cells and basal cells. This pattern of localization is similar to that shown by hepatocytes, proximal convoluted tubule cells of the kidney and a variety of other cell types. The function of this enzyme in tracheal epithelial cells is discussed.", "contents": "Ultrastructural localization of glucose 6-phosphatase activity in tracheal epithelium of the rat. Ultrastructural localization of glucose 6-phosphatase activity was studied in the tracheal epithelium of the rat. The reaction product for the enzyme activity was localized in the endoplasmic reticulum and nuclear envelope of all cell types composing the tracheal epithelium, namely ciliated cells, goblet cells, brush cells and basal cells. This pattern of localization is similar to that shown by hepatocytes, proximal convoluted tubule cells of the kidney and a variety of other cell types. The function of this enzyme in tracheal epithelial cells is discussed."} {"id": "PMID:166969", "title": "Mitochondrial structure in the rat adrenal cortex.", "content": "Two distinct classes of mitochondria are described in the normal adrenal cortex of the Sprague Dawley CFY rat. Polyaminar mitochondria were frequently observed in the zona fasciculata and zona reticularis, particularly after ACTH stimulation of the cortex resulting from cold-stress exposure. It is uncertain whether such organelles are degenerating forms, or whether they have a specific functional role related to steroidogenesis in the normal cortical cell. In both normal and stressed adrenal cortices, protrusions of the outer membrane of mitochondria were evident, and were often seen penetrating lipid droplets. It is suggested that these protrusions may have some significance in the transport of cholesterol from the lipid droplet to the inner mitochondrial memrane 'desmolase complex', thus facilitating side-chain cleavage of cholesterol to pregnenolone.", "contents": "Mitochondrial structure in the rat adrenal cortex. Two distinct classes of mitochondria are described in the normal adrenal cortex of the Sprague Dawley CFY rat. Polyaminar mitochondria were frequently observed in the zona fasciculata and zona reticularis, particularly after ACTH stimulation of the cortex resulting from cold-stress exposure. It is uncertain whether such organelles are degenerating forms, or whether they have a specific functional role related to steroidogenesis in the normal cortical cell. In both normal and stressed adrenal cortices, protrusions of the outer membrane of mitochondria were evident, and were often seen penetrating lipid droplets. It is suggested that these protrusions may have some significance in the transport of cholesterol from the lipid droplet to the inner mitochondrial memrane 'desmolase complex', thus facilitating side-chain cleavage of cholesterol to pregnenolone."} {"id": "PMID:166972", "title": "Influence of cycloheximide on the lung.", "content": "We examined the time course of the influence of cycloheximide on descending pressure-volume curves of excised lungs and on protein and lecithin synthesis and oxygen consumption by lung slices. We also looked at the influence of cycloheximide on granular pneumocyte ultrastructure. Excised lungs from cycloheximide-treated animals are more compliant than controls. After ventilation with air, lungs from control and cycloheximide animals show increased retractive forces and a shift to the right of the deflation P-V curve. Incubation at 38 degrees C for 30 min reverses these changes in control lungs, but not in lungs from cycloheximide-treated rabbits. There is no change in liquid delfation P-V curves after cycloheximide. Cycloheximide causes an immediate decrease of 50% in incorporation of radioactive leucine into protein by lung slices. Incorporation of radioactive palmitate into lecithin and oxygen consumption are also decreased by 50% 6 h after cycloheximide. Lamellar bodies in granular pneumocytes are smaller after cycloheximide. Cycloheximide causes a significant increase in the surface density of the lamellar body envelope. Cytoplasmic area of granular pneumocytes is increased after cycloheximide.", "contents": "Influence of cycloheximide on the lung. We examined the time course of the influence of cycloheximide on descending pressure-volume curves of excised lungs and on protein and lecithin synthesis and oxygen consumption by lung slices. We also looked at the influence of cycloheximide on granular pneumocyte ultrastructure. Excised lungs from cycloheximide-treated animals are more compliant than controls. After ventilation with air, lungs from control and cycloheximide animals show increased retractive forces and a shift to the right of the deflation P-V curve. Incubation at 38 degrees C for 30 min reverses these changes in control lungs, but not in lungs from cycloheximide-treated rabbits. There is no change in liquid delfation P-V curves after cycloheximide. Cycloheximide causes an immediate decrease of 50% in incorporation of radioactive leucine into protein by lung slices. Incorporation of radioactive palmitate into lecithin and oxygen consumption are also decreased by 50% 6 h after cycloheximide. Lamellar bodies in granular pneumocytes are smaller after cycloheximide. Cycloheximide causes a significant increase in the surface density of the lamellar body envelope. Cytoplasmic area of granular pneumocytes is increased after cycloheximide."} {"id": "PMID:166973", "title": "Comparison of virus recovery techniques for assessing the virucidal activity of disinfectant spray products.", "content": "A comparison was made of virus recovery from inoculated glass surfaces by 3 different viral recovery techniques used in spray test methods. On a total of 7, 5, and 5 observations, for the cover glass crushing, cotton swab rubbing, and microscopic slide shaking techniques, respectively, the log reduction of the median tissue culture infective dose (log TCID-50/ml) averaged 1.48, 2.57, and 2.22, the mean percentage recovery was 77.98, 61.55, and 66.94%, and the coefficient of variation was 4.37, 10.01, and 7.42%. The cover glass technique was found to be the least variable and the most effective and precise of the 3 methods.", "contents": "Comparison of virus recovery techniques for assessing the virucidal activity of disinfectant spray products. A comparison was made of virus recovery from inoculated glass surfaces by 3 different viral recovery techniques used in spray test methods. On a total of 7, 5, and 5 observations, for the cover glass crushing, cotton swab rubbing, and microscopic slide shaking techniques, respectively, the log reduction of the median tissue culture infective dose (log TCID-50/ml) averaged 1.48, 2.57, and 2.22, the mean percentage recovery was 77.98, 61.55, and 66.94%, and the coefficient of variation was 4.37, 10.01, and 7.42%. The cover glass technique was found to be the least variable and the most effective and precise of the 3 methods."} {"id": "PMID:166974", "title": "Detection of ochratoxin A in barley, using silica gel minicolumns.", "content": "A simplified procedure has been developed to detect ochratoxin A in cereals which can be used in the field where equipment for thin layer chromatography is not available. The procedure includes extraction of the acidified sample with chloroform, purification over sodium bicarbonate, and minicolumn chromatography. Under longwave ultraviolet light ochratoxin A appears as a blue-green fluorescent band at the lower end of the column. Contamination levels as low as 12 ppb can be detected by this method.", "contents": "Detection of ochratoxin A in barley, using silica gel minicolumns. A simplified procedure has been developed to detect ochratoxin A in cereals which can be used in the field where equipment for thin layer chromatography is not available. The procedure includes extraction of the acidified sample with chloroform, purification over sodium bicarbonate, and minicolumn chromatography. Under longwave ultraviolet light ochratoxin A appears as a blue-green fluorescent band at the lower end of the column. Contamination levels as low as 12 ppb can be detected by this method."} {"id": "PMID:166975", "title": "Quantitative fluorodensitometric determination and survey of aflatoxins in nutmeg.", "content": "A study is presented for the quantitative fluorodensitometric analysis of aflatoxins in spices, in particular nutmeg (Semen myristicae). Samples were extracted with chloroform, followed by silica gel column cleanup according to the AOAC officail first action method, 26.019(a), and by 2-dimensional thin layer chromatography according to the antidiagonal technique. The method includes a confirmatory test for aflatoxins by hemiacetal formation. The concentrations of aflatoxins in samples were determined by measurement of the fluorescent intensities of the separated aflatoxin spots from sample and standards on the same chromato-plate with a reflectance flying-spot sensitometer. With such a technique, a coefficient of variation value of 5.22 plus or minus 1.24% (P = 99%) was calculated for a series of 5 standard B-1 spots and averaged for 13 TLC plates, demonstrating the precision of the chromatographic and densitometric procedures. An average recovery of 108.4 plus or minus 5.8% (P = 95%) was obtained for 11 spiked nutmeg extracts (5.0-20.0 mu-g B-1 added/kg), whereas an average recovery of 92.6 plus or minus 4.9 (P = 95%) was established for 13 spiked nutmeg samples (5.0-20.0 mu-g B-1 added/kg). The coefficient of variation of the complete analytical procedure for ground nutmeg was 8.80%. In a survey on the occurrence of aflatoxins in 40 commercial nutmeg samples (covering 12 different brands) in The Netherlands, aflatoxins were detected in 30 ground samples (32 ground samples analyzed) in concentrations ranging from 1.0 to 23.2 mu-g B-1/kg or 2.7 to 36.5 mu-g B-1 + B-2 + G-1 + G-2/kg, whereas no aflatoxins were present in whole nutmeg kernels (8 samples analyzed). The lowest level of detection was 1.0 mu-g B-1/kg. In addition, 50 commercial spices consisting of 19 different types of commodities other than nutmeg wer assayed for aflatoxins according to the same procedure. No aflatoxins were detected in these samples, with the exception of 1 sample of bay leaf which contained 5.1 mu-g B-1/kg.", "contents": "Quantitative fluorodensitometric determination and survey of aflatoxins in nutmeg. A study is presented for the quantitative fluorodensitometric analysis of aflatoxins in spices, in particular nutmeg (Semen myristicae). Samples were extracted with chloroform, followed by silica gel column cleanup according to the AOAC officail first action method, 26.019(a), and by 2-dimensional thin layer chromatography according to the antidiagonal technique. The method includes a confirmatory test for aflatoxins by hemiacetal formation. The concentrations of aflatoxins in samples were determined by measurement of the fluorescent intensities of the separated aflatoxin spots from sample and standards on the same chromato-plate with a reflectance flying-spot sensitometer. With such a technique, a coefficient of variation value of 5.22 plus or minus 1.24% (P = 99%) was calculated for a series of 5 standard B-1 spots and averaged for 13 TLC plates, demonstrating the precision of the chromatographic and densitometric procedures. An average recovery of 108.4 plus or minus 5.8% (P = 95%) was obtained for 11 spiked nutmeg extracts (5.0-20.0 mu-g B-1 added/kg), whereas an average recovery of 92.6 plus or minus 4.9 (P = 95%) was established for 13 spiked nutmeg samples (5.0-20.0 mu-g B-1 added/kg). The coefficient of variation of the complete analytical procedure for ground nutmeg was 8.80%. In a survey on the occurrence of aflatoxins in 40 commercial nutmeg samples (covering 12 different brands) in The Netherlands, aflatoxins were detected in 30 ground samples (32 ground samples analyzed) in concentrations ranging from 1.0 to 23.2 mu-g B-1/kg or 2.7 to 36.5 mu-g B-1 + B-2 + G-1 + G-2/kg, whereas no aflatoxins were present in whole nutmeg kernels (8 samples analyzed). The lowest level of detection was 1.0 mu-g B-1/kg. In addition, 50 commercial spices consisting of 19 different types of commodities other than nutmeg wer assayed for aflatoxins according to the same procedure. No aflatoxins were detected in these samples, with the exception of 1 sample of bay leaf which contained 5.1 mu-g B-1/kg."} {"id": "PMID:166976", "title": "Role of adenylate kinase in the regulation of macromolecular biosynthesis in a putative mutant of Escherichia coli defective in membrane phospholipid biosynthesis.", "content": "The regulation of macromolecular biosynthesis was studied in a temperature-sensitive mutant of Escherichia coli previously identified as containing a single mutation causing a thermolabile sn-glycerol-3-phosphate acyltransferase, the first enzyme of the pathway for phospholipid biosynthesis. When this mutant was shifted to a nonpermissive temperature, phospholipid synthesis, as well as ribonucleic acid, deoxyribonucleic acid, and protein synthesis, decreased in a coordinate manner, suggesting the existence of a common regulatory mechanism. During the same time that the rate of macromolecular synthesis was decreasing at the nonpermissive temperature, the intracellular concentration of adenosine 5'-triphosphate dropped dramatically and the concentration of adenosine monophosphate increased. The concentration of adenosine 5'-diphosphate dropped, but not as markedly. The decrease in macromolecular synthesis and the changes in the adenine nucleotide concentrations can now be attributed to a thermolabile adenylate kinase. The inactivation of adenylate kinase prevented the cell from converting adenosine 5'-monophosphate to adenosine 5'-diphosphate and consequently from making adenosine 5'-triphosphate. This in turn caused a decrease in the rate of macromolecular synthesis and cell growth. Adenylate kinase, therefore, is a key enzyme in controlling the rate of cell growth. The nature of the possible relationship between adenylate kinase and glycerol-3-phosphate acyltransferase is discussed.", "contents": "Role of adenylate kinase in the regulation of macromolecular biosynthesis in a putative mutant of Escherichia coli defective in membrane phospholipid biosynthesis. The regulation of macromolecular biosynthesis was studied in a temperature-sensitive mutant of Escherichia coli previously identified as containing a single mutation causing a thermolabile sn-glycerol-3-phosphate acyltransferase, the first enzyme of the pathway for phospholipid biosynthesis. When this mutant was shifted to a nonpermissive temperature, phospholipid synthesis, as well as ribonucleic acid, deoxyribonucleic acid, and protein synthesis, decreased in a coordinate manner, suggesting the existence of a common regulatory mechanism. During the same time that the rate of macromolecular synthesis was decreasing at the nonpermissive temperature, the intracellular concentration of adenosine 5'-triphosphate dropped dramatically and the concentration of adenosine monophosphate increased. The concentration of adenosine 5'-diphosphate dropped, but not as markedly. The decrease in macromolecular synthesis and the changes in the adenine nucleotide concentrations can now be attributed to a thermolabile adenylate kinase. The inactivation of adenylate kinase prevented the cell from converting adenosine 5'-monophosphate to adenosine 5'-diphosphate and consequently from making adenosine 5'-triphosphate. This in turn caused a decrease in the rate of macromolecular synthesis and cell growth. Adenylate kinase, therefore, is a key enzyme in controlling the rate of cell growth. The nature of the possible relationship between adenylate kinase and glycerol-3-phosphate acyltransferase is discussed."} {"id": "PMID:166977", "title": "Multiple forms of cytochrome b in Mycobacterium phlei: kinetics of reduction.", "content": "The kinetics of reduction of the b-type cytochromes in the electron transport particles (ETP) from Mycobacterium phlei were studied with nicotinamide adenine dinucleotide, reduced form (NADH) or succinate as electron donors. There appeared to be three active cytochromes b in the ETP,bS563 and bS559, which were reducible by either substrate, and bN563, which was reducible by NADH but not by succinate. In the presence of adenosine 5'-triphosphate, a substantial increase in b563 reduction was observed with succinate at anaerobiosis. This was followed by a decrease in absorption. Adenosine 5'-triphosphate did not effect an increase in cytochrome b563 reduction at transition with NADH, but the occurrence of a secondary decrease in absorption was reflected in a decrease in total enzymatic reduction. The adenosine 5'-triphosphate effect was altered in trypsin-treated ETP, and abolished by uncoupling agents or by removal of the coupling factor-latent adenosine triphosphatase. In the presence of a supernatant fraction obtained during the preparation of the ETP, b563 reduction with succinate was greatly increased. A smaller increase was observed with NADH. Cytochrome b reduction was also studied in ETP inhibited by 2-n-nonylhydroxyquinoline-N-oxide, which appears to inhibit at bS563. On the basis of these data the interrelationships among the b-type cytochromes can be described in relation to the M. phlei electron transport chain.", "contents": "Multiple forms of cytochrome b in Mycobacterium phlei: kinetics of reduction. The kinetics of reduction of the b-type cytochromes in the electron transport particles (ETP) from Mycobacterium phlei were studied with nicotinamide adenine dinucleotide, reduced form (NADH) or succinate as electron donors. There appeared to be three active cytochromes b in the ETP,bS563 and bS559, which were reducible by either substrate, and bN563, which was reducible by NADH but not by succinate. In the presence of adenosine 5'-triphosphate, a substantial increase in b563 reduction was observed with succinate at anaerobiosis. This was followed by a decrease in absorption. Adenosine 5'-triphosphate did not effect an increase in cytochrome b563 reduction at transition with NADH, but the occurrence of a secondary decrease in absorption was reflected in a decrease in total enzymatic reduction. The adenosine 5'-triphosphate effect was altered in trypsin-treated ETP, and abolished by uncoupling agents or by removal of the coupling factor-latent adenosine triphosphatase. In the presence of a supernatant fraction obtained during the preparation of the ETP, b563 reduction with succinate was greatly increased. A smaller increase was observed with NADH. Cytochrome b reduction was also studied in ETP inhibited by 2-n-nonylhydroxyquinoline-N-oxide, which appears to inhibit at bS563. On the basis of these data the interrelationships among the b-type cytochromes can be described in relation to the M. phlei electron transport chain."} {"id": "PMID:166978", "title": "Replication of R-factor R1 in Scherichia coli K-12 at different growth rates.", "content": "The R-factor R1drd-19 mediates resistance to beta-lactam antibiotics via a beta-lactamase. A strain of Escherichia coli K-12 carrying R1drd-19 was grown at different growth rates by using different carbon sources. The specific rate of production of the R1 beta-lactamase increased linearly with the growth rate and with the gene dosage. The content of R1 deoxyribonucleic acid was estimated by alkaline sucrose gradient centrifugation and by analysis of the specific rate of beta-lactamase synthesis in nutritional shift-up experiments and was found to decrease fivefold when the growth rate was increased from 0.4 to 1.8 doublings per h. The number of R1 molecules per cell decreased from six to two in the same growth range. The presence of the plasmid affected the mean cell size significantly; at a growth rate of 0.4 doublings per h the R-+ cells were on the average 50% bigger than the R-minus cells, whereas the effect was less than 10% at a growth rate of 1.8 doublings per h. Several reports in the leterature state that the initiation mass of chromosome replication is constant. In this paper it is shown that the initiation mass of R1 replication is proportional to the growth rate. Thus, the replication of the plasmid R1 and of the chromosome are independently regulated processes. It is argued that plasmid replication is under negative control.", "contents": "Replication of R-factor R1 in Scherichia coli K-12 at different growth rates. The R-factor R1drd-19 mediates resistance to beta-lactam antibiotics via a beta-lactamase. A strain of Escherichia coli K-12 carrying R1drd-19 was grown at different growth rates by using different carbon sources. The specific rate of production of the R1 beta-lactamase increased linearly with the growth rate and with the gene dosage. The content of R1 deoxyribonucleic acid was estimated by alkaline sucrose gradient centrifugation and by analysis of the specific rate of beta-lactamase synthesis in nutritional shift-up experiments and was found to decrease fivefold when the growth rate was increased from 0.4 to 1.8 doublings per h. The number of R1 molecules per cell decreased from six to two in the same growth range. The presence of the plasmid affected the mean cell size significantly; at a growth rate of 0.4 doublings per h the R-+ cells were on the average 50% bigger than the R-minus cells, whereas the effect was less than 10% at a growth rate of 1.8 doublings per h. Several reports in the leterature state that the initiation mass of chromosome replication is constant. In this paper it is shown that the initiation mass of R1 replication is proportional to the growth rate. Thus, the replication of the plasmid R1 and of the chromosome are independently regulated processes. It is argued that plasmid replication is under negative control."} {"id": "PMID:166979", "title": "Organization and control in the arginine biosynthetic pathway of Neurospora.", "content": "Eight enzymes involved in the conversion of acetylglutamate to arginine in Neurospora crassa were studied. The data indicate that of three enzymes early in the sequence, only the first, acetylglutamate kinase, is a nonorganellar enzyme. The next two, N-acetyl-gamma-glutamyl-phosphate reductase and acetylornithine aminotransferase, are in the mitochondrion, which was previously shown to contain the subsequent enzymes: acetylornithine-glutamate acetyltransferase, ornithine carbamyltransferase, and carbamyl-phosphate synthetase A (arginine specific). The last two enzymes of the pathway, argininosuccinate synthetase and argininosuccinate lyase, were previously shown to be cytosolic. All enzymes but one have low amplitudes or repression. Their levels respond little to arginine excess and are about twofold elevated (threefold for ornithine carbamyltransferase) as a result of arginine limitation in the arg-12-8 strain. No restriction of the incorporation of mitochondrial enzymes into mitochondria could be detected when the levels of these enzymes were elevated. Two enzymes, acetylglutamate kinase and carbamyl-phosphate synthetase A, which initiate the synthesis of the ornithine and guanidino moieties of arginine, respectively, show the lowest specific activities in crude extract. These enzymes display special regulatroy features. Acetylglutamate kinase, which has a typically low amplitude of repression, is subject to feedback inhibition. Carbamyl-phosphate synthetase A is wholly insensitive to arginine or citrulline in vitro or in vivo, but displays a very large amplitude of repression (about 60-fold). It is unique in that it can be almost completely repressed by growth of mycelia in excess arginine. These data suggest that mitochondrial localization may be incompatible with a mechanism of feedback inhibition by a cytosolic effector, arginine. Further, they suggest that the high repressibility of carbamyl-phosphate synthetase A compensates for its feedback insensitivity.", "contents": "Organization and control in the arginine biosynthetic pathway of Neurospora. Eight enzymes involved in the conversion of acetylglutamate to arginine in Neurospora crassa were studied. The data indicate that of three enzymes early in the sequence, only the first, acetylglutamate kinase, is a nonorganellar enzyme. The next two, N-acetyl-gamma-glutamyl-phosphate reductase and acetylornithine aminotransferase, are in the mitochondrion, which was previously shown to contain the subsequent enzymes: acetylornithine-glutamate acetyltransferase, ornithine carbamyltransferase, and carbamyl-phosphate synthetase A (arginine specific). The last two enzymes of the pathway, argininosuccinate synthetase and argininosuccinate lyase, were previously shown to be cytosolic. All enzymes but one have low amplitudes or repression. Their levels respond little to arginine excess and are about twofold elevated (threefold for ornithine carbamyltransferase) as a result of arginine limitation in the arg-12-8 strain. No restriction of the incorporation of mitochondrial enzymes into mitochondria could be detected when the levels of these enzymes were elevated. Two enzymes, acetylglutamate kinase and carbamyl-phosphate synthetase A, which initiate the synthesis of the ornithine and guanidino moieties of arginine, respectively, show the lowest specific activities in crude extract. These enzymes display special regulatroy features. Acetylglutamate kinase, which has a typically low amplitude of repression, is subject to feedback inhibition. Carbamyl-phosphate synthetase A is wholly insensitive to arginine or citrulline in vitro or in vivo, but displays a very large amplitude of repression (about 60-fold). It is unique in that it can be almost completely repressed by growth of mycelia in excess arginine. These data suggest that mitochondrial localization may be incompatible with a mechanism of feedback inhibition by a cytosolic effector, arginine. Further, they suggest that the high repressibility of carbamyl-phosphate synthetase A compensates for its feedback insensitivity."} {"id": "PMID:166980", "title": "Ultrastructal morphology of some prokaryotic microorganisms associated with the hindgut of cockroaches.", "content": "Scanning electron microscopy and transmission electron microscopy have been used to visualize the morphology and ultrastructure of two types of microorganisms in the hindgut of the cockroach Blaberus posticus. Both organisms, designated as either short or long rods, are attached to chitinous projections from the gut wall. Micrographs suggest that the organisms are prokaryotic with a cell wall complex characteristic of gram-negative bacteria. However, certain differences were noted between the cell wall complex of the two types. Two forms of the long-rod type were noted, with one form appearing to be a \"degenerate\" or \"transitional\" cell. In the degenerate cells, vesicles are observed that often are contiguous with the cytoplasmic membrane. There are indications that the long-rod type may divide by longitudinal fission. Neither the short- nor long-rod type has been cultivated in its respective recognizable form.", "contents": "Ultrastructal morphology of some prokaryotic microorganisms associated with the hindgut of cockroaches. Scanning electron microscopy and transmission electron microscopy have been used to visualize the morphology and ultrastructure of two types of microorganisms in the hindgut of the cockroach Blaberus posticus. Both organisms, designated as either short or long rods, are attached to chitinous projections from the gut wall. Micrographs suggest that the organisms are prokaryotic with a cell wall complex characteristic of gram-negative bacteria. However, certain differences were noted between the cell wall complex of the two types. Two forms of the long-rod type were noted, with one form appearing to be a \"degenerate\" or \"transitional\" cell. In the degenerate cells, vesicles are observed that often are contiguous with the cytoplasmic membrane. There are indications that the long-rod type may divide by longitudinal fission. Neither the short- nor long-rod type has been cultivated in its respective recognizable form."} {"id": "PMID:166981", "title": "Mechanism of the isomerization of isopentenyl pyrophosphate in Rhodotorual rubra-1.", "content": "Stereospecifically labeled mevalonic acid was incorporated into the carotenoids of Rhodotorula. The randomized results are discussed in relation to mechanisms proposed for the conversion of isopentenyl pyrophosphate to dimethylallyl pyrophosphate and the prenol transferase enzyme system to Rhondotorula rubra.", "contents": "Mechanism of the isomerization of isopentenyl pyrophosphate in Rhodotorual rubra-1. Stereospecifically labeled mevalonic acid was incorporated into the carotenoids of Rhodotorula. The randomized results are discussed in relation to mechanisms proposed for the conversion of isopentenyl pyrophosphate to dimethylallyl pyrophosphate and the prenol transferase enzyme system to Rhondotorula rubra."} {"id": "PMID:166982", "title": "Increased ouabain-sensitive 86Rb+ uptake and sodium and potassium ion-activated adenosine triphosphatase activity in transformed cell lines.", "content": "During the log phase of growth both the active, ouabain-sensitive K+ uptake, measured as 86Rb+, and the sodium and potassium ion-activated ATPase ((Na+ + K+)-ATPase) activity of SV40-transformed 3T3 cells were 2.5-and 5,5-fold higher, respectively, than in untransformed 3T3 cells. A similar higher active K+ uptake was found for Rous sarcoma virus and SV40-transformed baby hamster kidney cells compared with untransformed BHK cells. The active K+ uptake in SV403T3 and normal 3T3 cells decreased when the growth rate of both cell types diminished. Reduction in ouabain-sensitive ATP hydrolysis only occurred later, however, when appreciable decreases in cell viability were seen. Arrhenius plots of the (Na+ + K+)-ATPase activity of SV403T3 cells indicated a discontinuity at 24 degrees, whereas no similar discontinuity was indicated for 3T3 cells. The consequences of elevated K+ transport and (Na+ + K+)-ATPase activity in transformed cells and the possibility that the increased activity might be related to differences inphospholipid fatty acyl chain fluidity are discussed.", "contents": "Increased ouabain-sensitive 86Rb+ uptake and sodium and potassium ion-activated adenosine triphosphatase activity in transformed cell lines. During the log phase of growth both the active, ouabain-sensitive K+ uptake, measured as 86Rb+, and the sodium and potassium ion-activated ATPase ((Na+ + K+)-ATPase) activity of SV40-transformed 3T3 cells were 2.5-and 5,5-fold higher, respectively, than in untransformed 3T3 cells. A similar higher active K+ uptake was found for Rous sarcoma virus and SV40-transformed baby hamster kidney cells compared with untransformed BHK cells. The active K+ uptake in SV403T3 and normal 3T3 cells decreased when the growth rate of both cell types diminished. Reduction in ouabain-sensitive ATP hydrolysis only occurred later, however, when appreciable decreases in cell viability were seen. Arrhenius plots of the (Na+ + K+)-ATPase activity of SV403T3 cells indicated a discontinuity at 24 degrees, whereas no similar discontinuity was indicated for 3T3 cells. The consequences of elevated K+ transport and (Na+ + K+)-ATPase activity in transformed cells and the possibility that the increased activity might be related to differences inphospholipid fatty acyl chain fluidity are discussed."} {"id": "PMID:166983", "title": "Adenylate kinase of human erythrocyte. Isolation and properties of the predominant inherited form.", "content": "Adenylate kinase exists in the human erythrocyte in a number of molecular forms with two allels at a single polymorphic locus coding for most of the enzyme forms. The predominant enzyme form, AK a, was purified to constant specific activity in excess of 3000 and appeared homogeneous by chromatography, electrophoresis, and ultracentrifugation. Sedimentation velocity and partial specific volume measurments of AK a yielded values of s20,w = 2.1 S and 0.722 cm-3per g. The molecular weight of the native enzyme was estimated to be 22,500 by sedimentation equilibrium and gel filtration analyses. The molecular weight of the denatured enzyme did not differ, indicating an absence of subunit structure in confirmation of genetic evidence of a single locus coding for the enzyme. The isolated enzyme demonstrated remarkable stability to denaturants (heat, guanidine HCl, urea) in the presence of appropriate stabilizing agents and could not be distinguished from rabbit muscle enzyme on this basis (as well as by a number of other kinetic and physicochemical parameters). The erythrocyte adenylate kinases have a common molecular size but differ in their charge properties. They demonstrate anomalous electrophoretic behavior, migrating anionic to hemoglobin in starch gel, yet exhibit isoelectric points considerably alkaline to hemoglobin (e.g. AK a, pI = 9.0) by isoelectric focusing.", "contents": "Adenylate kinase of human erythrocyte. Isolation and properties of the predominant inherited form. Adenylate kinase exists in the human erythrocyte in a number of molecular forms with two allels at a single polymorphic locus coding for most of the enzyme forms. The predominant enzyme form, AK a, was purified to constant specific activity in excess of 3000 and appeared homogeneous by chromatography, electrophoresis, and ultracentrifugation. Sedimentation velocity and partial specific volume measurments of AK a yielded values of s20,w = 2.1 S and 0.722 cm-3per g. The molecular weight of the native enzyme was estimated to be 22,500 by sedimentation equilibrium and gel filtration analyses. The molecular weight of the denatured enzyme did not differ, indicating an absence of subunit structure in confirmation of genetic evidence of a single locus coding for the enzyme. The isolated enzyme demonstrated remarkable stability to denaturants (heat, guanidine HCl, urea) in the presence of appropriate stabilizing agents and could not be distinguished from rabbit muscle enzyme on this basis (as well as by a number of other kinetic and physicochemical parameters). The erythrocyte adenylate kinases have a common molecular size but differ in their charge properties. They demonstrate anomalous electrophoretic behavior, migrating anionic to hemoglobin in starch gel, yet exhibit isoelectric points considerably alkaline to hemoglobin (e.g. AK a, pI = 9.0) by isoelectric focusing."} {"id": "PMID:166984", "title": "Thf complete amino acid sequence of C-I (apoLp-Ser), an apolipoprotein from human very low density lipoproteins.", "content": "C-I was prepared from very low density lipoproteins of patients with familial type V hyperliporproteinemia. Peptides from tryptic digests of unmodified and succinylated C-I, chymotryptic peptides, and the products of cayanogen bromide cleavage were isolated and characterized. Sequence analysis of tryptic peptides was performed by the dansyl (5-dimethylaminonaphthalene-1-sulfonyl) technique and hydrolytic regeneration of the amino acid residues from the phenylthiocarbamyl derivatives. Alignment of the tryptic fragments within the cyanogen bromide and succinyl-tryptic peptides was confirmed by the overlap chymotryptic peptides. The complete amino acid sequence of C-I, 57 residues in length, does not reveal any obvious basis for its lipophilic properties.", "contents": "Thf complete amino acid sequence of C-I (apoLp-Ser), an apolipoprotein from human very low density lipoproteins. C-I was prepared from very low density lipoproteins of patients with familial type V hyperliporproteinemia. Peptides from tryptic digests of unmodified and succinylated C-I, chymotryptic peptides, and the products of cayanogen bromide cleavage were isolated and characterized. Sequence analysis of tryptic peptides was performed by the dansyl (5-dimethylaminonaphthalene-1-sulfonyl) technique and hydrolytic regeneration of the amino acid residues from the phenylthiocarbamyl derivatives. Alignment of the tryptic fragments within the cyanogen bromide and succinyl-tryptic peptides was confirmed by the overlap chymotryptic peptides. The complete amino acid sequence of C-I, 57 residues in length, does not reveal any obvious basis for its lipophilic properties."} {"id": "PMID:166985", "title": "Piericiden A sensitivity, site 1 phosphorylation, and reduced nicotinamide adenine dinucleotide dehydrogenase during iron-limited growth of Candida utilis.", "content": "It has been reported that cells of Candida utilis, grown in continuous culture under iron-limited conditions, develop site 1 phosphorylation, without the appearance of piericidin sensitivity and without changes in the iron-sulfur centers of NADH dehydrogenase, on aeration in the presence of cycloheximide, as well as on increasing the supply of iron during growth. These findings were reinvestigated in the present study. The parameters and properties followed during these transitions were sensitivity of NADH oxidation to piericidin, presence or absence of coupling site 1, EPR signals appearing on reduction with NADH or dithionite, the specific activities of NADH oxidase, NADH-ferricyanide reductase, and NADH-5-hydroxy-1,4-naphthoquinone (juglone) reductase, and the kinetic behavior of NADH dehydrogenase in the ferricyanide assay. Monitoring the rates of oxidation of NADH in submitochondrial particles with artificial oxidants, observing the kinetics of the ferricyanide assay, and measuring the concentration of iron-sulfur centers elicited by EPR permitted ascertaining the type of NADH dehydrogenase present and its relative concentration in different experimental situations. It was found that on gradually increasing the concentration of iron during continuous culture (transition from ironlimited to iron- and substrate-limited growth), as well as on aeration of iron-limited cells, coupling site 1, piericidin sensitivity, NADH-ferricyanide activity, and iron-sulfur centers 1 and 2 increased concurrently, with concomitant decline of NADH-juglone reductase activity. Cycloheximide prevented all these changes. Iron-sulfur centers 3 plus 4 underwent relatively little increase during these transitions. It is concluded that in both of these experimental conditions a replacement of the type of NADH dehydrogenase present in exponential phase cells by that characteristic of stationary phase cells occurs and that the appearance of site 1 phosphorylation, piercidin sensitivity, and iron-sulfur centers 1 plus 2, all associated with the latter enzyme, is a consequence of this replacement. No evidence was found for the development of coupling site 1 without the appearance of piericidin sensir th", "contents": "Piericiden A sensitivity, site 1 phosphorylation, and reduced nicotinamide adenine dinucleotide dehydrogenase during iron-limited growth of Candida utilis. It has been reported that cells of Candida utilis, grown in continuous culture under iron-limited conditions, develop site 1 phosphorylation, without the appearance of piericidin sensitivity and without changes in the iron-sulfur centers of NADH dehydrogenase, on aeration in the presence of cycloheximide, as well as on increasing the supply of iron during growth. These findings were reinvestigated in the present study. The parameters and properties followed during these transitions were sensitivity of NADH oxidation to piericidin, presence or absence of coupling site 1, EPR signals appearing on reduction with NADH or dithionite, the specific activities of NADH oxidase, NADH-ferricyanide reductase, and NADH-5-hydroxy-1,4-naphthoquinone (juglone) reductase, and the kinetic behavior of NADH dehydrogenase in the ferricyanide assay. Monitoring the rates of oxidation of NADH in submitochondrial particles with artificial oxidants, observing the kinetics of the ferricyanide assay, and measuring the concentration of iron-sulfur centers elicited by EPR permitted ascertaining the type of NADH dehydrogenase present and its relative concentration in different experimental situations. It was found that on gradually increasing the concentration of iron during continuous culture (transition from ironlimited to iron- and substrate-limited growth), as well as on aeration of iron-limited cells, coupling site 1, piericidin sensitivity, NADH-ferricyanide activity, and iron-sulfur centers 1 and 2 increased concurrently, with concomitant decline of NADH-juglone reductase activity. Cycloheximide prevented all these changes. Iron-sulfur centers 3 plus 4 underwent relatively little increase during these transitions. It is concluded that in both of these experimental conditions a replacement of the type of NADH dehydrogenase present in exponential phase cells by that characteristic of stationary phase cells occurs and that the appearance of site 1 phosphorylation, piercidin sensitivity, and iron-sulfur centers 1 plus 2, all associated with the latter enzyme, is a consequence of this replacement. No evidence was found for the development of coupling site 1 without the appearance of piericidin sensir th"} {"id": "PMID:166986", "title": "The distribution and dissociation of cyclic adenosine 3':5'-monophosphate-dependent protein kinases in adipose, cardiac, and other tissues.", "content": "In crude extracts of adipose tissue the protein kinase dissociates slowly at 30 degrees into regulatory and catalytic subunits in the presence of 700 mug per ml of histone or 0.5 M NaCl. If the kinase is first dissociated by adding 10 muM adenosine 3':5'-monophosphate (cAMP), reassociation occurs instantaneously after removal of the cAMP by Sephadex G-25 chromatography. In contrast, in crude xtracts of heart, the protein kinase dissociates rapidly in the presence of 700 mug per ml of histone or 0.5 M NaCl and reassociates slowly after removal of cAMP. These differences are accounted for by the existence of two types of protein kinases in these tissues, referred to as types I and II. DEAE-cellulose chromatography of extracts of adipose tissue produces only one peak of cAMP-dependent protein kinase activity (type II) which elutes between 0.15 and 0.25 M NaCl. Similar chromatography of heart extracts resolves enzyme activity into two peaks; a type I enzyme which elutes between 0.05 and 0.1 M and predominates (greater than 75% of total activity), and a type II enzyme which elutes between 0.15 and 0.25 M NaCl. The dissociation properties of the types I and II enzymes from heart and adipose tissue are retained after partial purification by DEAE-cellulose and Sepharose 6B chromatography. Rechromatography of the separated peaks of the cardiac enzymes does not change the elution pattern. Sucrose density gradient centrifugation and gel filtration studies indicate that the molecular weights of these enzymes are very similar. The type II enzyme isolated by DEAE-cellulose chromatography of heart extracts resembles the adipose tissue enzyme, i.e. it undergoes slow dissociation at 30 degrees in the presence of histone or 0.5 M NaCl. The adipose tissue kinase and the heart type II kinase are not identical, however, since they do not elute at exactly the same point on DEAE-cellulose columns. A survey of several tissues indicates the presence of type I and II protein kinases similar to the enzymes in adipose tissue and heart as determined by DEAE-cellulose chromatography of crude extracts and by dissociation of the enzymes with histone. The presence of MgATP prevents dissociation of type I enzyme from heart by 0.5 M NaCl or histone. The profile of the enzyme on DEAE-cellulose, however, is not changed...", "contents": "The distribution and dissociation of cyclic adenosine 3':5'-monophosphate-dependent protein kinases in adipose, cardiac, and other tissues. In crude extracts of adipose tissue the protein kinase dissociates slowly at 30 degrees into regulatory and catalytic subunits in the presence of 700 mug per ml of histone or 0.5 M NaCl. If the kinase is first dissociated by adding 10 muM adenosine 3':5'-monophosphate (cAMP), reassociation occurs instantaneously after removal of the cAMP by Sephadex G-25 chromatography. In contrast, in crude xtracts of heart, the protein kinase dissociates rapidly in the presence of 700 mug per ml of histone or 0.5 M NaCl and reassociates slowly after removal of cAMP. These differences are accounted for by the existence of two types of protein kinases in these tissues, referred to as types I and II. DEAE-cellulose chromatography of extracts of adipose tissue produces only one peak of cAMP-dependent protein kinase activity (type II) which elutes between 0.15 and 0.25 M NaCl. Similar chromatography of heart extracts resolves enzyme activity into two peaks; a type I enzyme which elutes between 0.05 and 0.1 M and predominates (greater than 75% of total activity), and a type II enzyme which elutes between 0.15 and 0.25 M NaCl. The dissociation properties of the types I and II enzymes from heart and adipose tissue are retained after partial purification by DEAE-cellulose and Sepharose 6B chromatography. Rechromatography of the separated peaks of the cardiac enzymes does not change the elution pattern. Sucrose density gradient centrifugation and gel filtration studies indicate that the molecular weights of these enzymes are very similar. The type II enzyme isolated by DEAE-cellulose chromatography of heart extracts resembles the adipose tissue enzyme, i.e. it undergoes slow dissociation at 30 degrees in the presence of histone or 0.5 M NaCl. The adipose tissue kinase and the heart type II kinase are not identical, however, since they do not elute at exactly the same point on DEAE-cellulose columns. A survey of several tissues indicates the presence of type I and II protein kinases similar to the enzymes in adipose tissue and heart as determined by DEAE-cellulose chromatography of crude extracts and by dissociation of the enzymes with histone. The presence of MgATP prevents dissociation of type I enzyme from heart by 0.5 M NaCl or histone. The profile of the enzyme on DEAE-cellulose, however, is not changed..."} {"id": "PMID:166987", "title": "The regulated catabolism of endogenous and exogenous phosphatidylinositol by Saccharomyces cerevisiae leading to extracellular glycerophosphorylinositol and inositol.", "content": "It was previously shown that phosphatidylinositol catabolism leads to the accumulation of glycerophosphorylinositol in the culture medium of Saccharomyces cerevisiae. We now find that lack of an energy source (glucose) reduces the formation of glycerophosphorylinositol and increases extra-cellular inositol. This situation is reversed by refeeding glucose. [3H]Phosphatidylinositol is the precursor of extra-cellular [3H]inositol with energy-starved cells. Extracellular glycerophosphorylcholine and glycerophosphorylethanolamine accumulate more slowly than glycerophosphorylinositol in the growth medium and do not appear to be a strongly affected by energy starvation. Phosphatidylinositol deacylation appears to occur at the cell surface in a regulated manner. Exogenously added phosphatidylinositol apparently does not mix randomly with the endogenous pool since it is not converted to either inositol-containing sphingolipid or to diphosphoinositide, both previously shown to be derived in part from cellular phosphatidylinositol. Labeled exogenous phosphatidylinositol is, however, quantitatively converted to glycerophosphorylinositol with the probable intermediat formation of monoacyl-glycerophosphorylinositol. Breakdown of exogenous phosphatidylinositol requires an energy source and does not lead to free inositol. Deacylation of exogenously added 1-acyl-glycerophosphorylinositol occurs much faster than deacylation of phosphatidylinositol and does not require an energy source. Glycerophosphorylethanolamine formation from exogenous phosphatidylethanolamine occurs about as fast as the breakdown of phosphatidylinositol and is also inhibited in the absence of energy source. The much slower deacylation of exogenous phosphatidylcholine was also affected by an energy source. Glycerophosphorylinosiyolaccumulates in the culture medium of Kloeckera apiculata, Saccharomyces carlsbergenis, and Neurospora crassa.", "contents": "The regulated catabolism of endogenous and exogenous phosphatidylinositol by Saccharomyces cerevisiae leading to extracellular glycerophosphorylinositol and inositol. It was previously shown that phosphatidylinositol catabolism leads to the accumulation of glycerophosphorylinositol in the culture medium of Saccharomyces cerevisiae. We now find that lack of an energy source (glucose) reduces the formation of glycerophosphorylinositol and increases extra-cellular inositol. This situation is reversed by refeeding glucose. [3H]Phosphatidylinositol is the precursor of extra-cellular [3H]inositol with energy-starved cells. Extracellular glycerophosphorylcholine and glycerophosphorylethanolamine accumulate more slowly than glycerophosphorylinositol in the growth medium and do not appear to be a strongly affected by energy starvation. Phosphatidylinositol deacylation appears to occur at the cell surface in a regulated manner. Exogenously added phosphatidylinositol apparently does not mix randomly with the endogenous pool since it is not converted to either inositol-containing sphingolipid or to diphosphoinositide, both previously shown to be derived in part from cellular phosphatidylinositol. Labeled exogenous phosphatidylinositol is, however, quantitatively converted to glycerophosphorylinositol with the probable intermediat formation of monoacyl-glycerophosphorylinositol. Breakdown of exogenous phosphatidylinositol requires an energy source and does not lead to free inositol. Deacylation of exogenously added 1-acyl-glycerophosphorylinositol occurs much faster than deacylation of phosphatidylinositol and does not require an energy source. Glycerophosphorylethanolamine formation from exogenous phosphatidylethanolamine occurs about as fast as the breakdown of phosphatidylinositol and is also inhibited in the absence of energy source. The much slower deacylation of exogenous phosphatidylcholine was also affected by an energy source. Glycerophosphorylinosiyolaccumulates in the culture medium of Kloeckera apiculata, Saccharomyces carlsbergenis, and Neurospora crassa."} {"id": "PMID:166988", "title": "Equilibrium and water proton relaxation rate enhancement properties of formyltetrahydrofolate synthetase-manganous ion-substrate complexes.", "content": "Binding of Mn(pi)-nucleotide complexes to the enzyme formyltertrahydrofolate synthetase (EC 6.3.4.3) from Clostridium cylindrosporum has been examined in the presence and absence of other substrates by solvent proton relaxation mearurements. MnADP and MnATP form ternary complexes with the enzyme with highly enhanced proton relaxation rates for water. The enhancement parameters, epsilont, for the MnADP and MnATP ternary complexes are 19.8 and 12.5, respectively at 24.3 MHZ and 25 degrees. Titration curves with constant total concentrations of enzyme and Mn(pi) with variable nucleotide concentration are similar to those observed in similar titrations with the endp and MnATP are 175 muM and 64 muM, respectively at 25 degrees. Addition of tetrahydrofolate to solutions of the MnADP OR MnATP ternary complexes lowers the observed relaxation enhancement markedly. An analysis of titration curves with constant total concentrations of enzyme, Mn(pi), and nucleotide with variable tetrahydrofolate concentration gives the dissociation constant for tetrahydrofolate from the respective quaternary complexes. The affinity of the enzyme for tetrahydrofolate is increased 6-fold when MnADP is present at the active site whereas a 3-fold increase is observed with MnATP present. Furthermore, there is a 20-fold increase in the enzyme's affinity for tetrahydrofolate when both MnADP and the third substrate, formate, are present. The observed relaxation rate of water for solutions of the complex, enzyme-MnADP-tetrahydrofolate-formate, is deenhanced with respect to the rate observed for the simple aquo-Mn(pi) solution. Addition of nitrate to solutions of the above complex increases the affinity of the enzyme for tetrahydrofolate and MnADP by an additional factor of 5 and lowers the relaxation rate further to a value which approaches that for solutions of the enzyme and substrates which lack the paramagnetic cation.", "contents": "Equilibrium and water proton relaxation rate enhancement properties of formyltetrahydrofolate synthetase-manganous ion-substrate complexes. Binding of Mn(pi)-nucleotide complexes to the enzyme formyltertrahydrofolate synthetase (EC 6.3.4.3) from Clostridium cylindrosporum has been examined in the presence and absence of other substrates by solvent proton relaxation mearurements. MnADP and MnATP form ternary complexes with the enzyme with highly enhanced proton relaxation rates for water. The enhancement parameters, epsilont, for the MnADP and MnATP ternary complexes are 19.8 and 12.5, respectively at 24.3 MHZ and 25 degrees. Titration curves with constant total concentrations of enzyme and Mn(pi) with variable nucleotide concentration are similar to those observed in similar titrations with the endp and MnATP are 175 muM and 64 muM, respectively at 25 degrees. Addition of tetrahydrofolate to solutions of the MnADP OR MnATP ternary complexes lowers the observed relaxation enhancement markedly. An analysis of titration curves with constant total concentrations of enzyme, Mn(pi), and nucleotide with variable tetrahydrofolate concentration gives the dissociation constant for tetrahydrofolate from the respective quaternary complexes. The affinity of the enzyme for tetrahydrofolate is increased 6-fold when MnADP is present at the active site whereas a 3-fold increase is observed with MnATP present. Furthermore, there is a 20-fold increase in the enzyme's affinity for tetrahydrofolate when both MnADP and the third substrate, formate, are present. The observed relaxation rate of water for solutions of the complex, enzyme-MnADP-tetrahydrofolate-formate, is deenhanced with respect to the rate observed for the simple aquo-Mn(pi) solution. Addition of nitrate to solutions of the above complex increases the affinity of the enzyme for tetrahydrofolate and MnADP by an additional factor of 5 and lowers the relaxation rate further to a value which approaches that for solutions of the enzyme and substrates which lack the paramagnetic cation."} {"id": "PMID:166989", "title": "Electron paramagnetic resonance and water proton relaxation rate studies of formyltetrahydrofolate synthetase-manganous ion complexes. Evidence for involvement of substrates in the promotion of a catalytically competent active site.", "content": "Conformational properties of the active site of formyltetrahydrofolate synthetase from Clostridium cylindrosorum have been examined by EPR spectroscopy and by solvent proton relaxation rate (PPR) studies of manganous complexes with the enzyme. Ternary enzyme-Mn-nucleotide complexes give EPR spectra which are very similar to those for the binary Mn-nucleotide complexes. However, upon addition of tetrahydrofolate to form the quaternary complexes, enzyme-MnADP-tetrahydrofolate and enzyme MnATP-tetrahydrofolate the EPR line shapes are changed substantially. Spectra for the quaternary complexes exhibit narrow line widths, and the splitting patterns are characteristic of a slightly asymmetric electronic environment for the bound Mn(II). Addition of formate to the ADP quatenary complex induces a further significant narrowing of the EPR line widths, although in the absence of tetrahydrofolate, formate does not influence the EPR spectrum for the enzyme-MnADP species. Both Pi and nitrate cause changes in the EPR patterns for the higher complexes of the enzyme which involve both ADP and tetrahydololate. However, the Pi effect is not influenced by the presence of formate whereas the characteristic effect of nitrate is potentiated only when formate is present. EPR sectra for the thernary complex with the beta, gamma-methylene analog of ATP App(CH2)p differ significantly from spectra for the binary App(CH)p complex is not influenced by further additions of tetrahydrofolate and of tetrahydorfolate and formate. The failure of spectra for the App(CH)p complex to respond to additions of the other substrates for the reaction is in marked contrast to the behavior found for the natural nucleotide substrates and is tentatively attributed to the lack of a protein-mediated interaction between the nucleotide and tetrahydrofolate binding sites in the analog complex. The frequency dependence of solvent PRR in the presence of the various complexes allows an estimate of the correlation times for electron-nuclear dipolar interaction and thereby the extent of hydration of the bound Mn(II) among the various complexes..", "contents": "Electron paramagnetic resonance and water proton relaxation rate studies of formyltetrahydrofolate synthetase-manganous ion complexes. Evidence for involvement of substrates in the promotion of a catalytically competent active site. Conformational properties of the active site of formyltetrahydrofolate synthetase from Clostridium cylindrosorum have been examined by EPR spectroscopy and by solvent proton relaxation rate (PPR) studies of manganous complexes with the enzyme. Ternary enzyme-Mn-nucleotide complexes give EPR spectra which are very similar to those for the binary Mn-nucleotide complexes. However, upon addition of tetrahydrofolate to form the quaternary complexes, enzyme-MnADP-tetrahydrofolate and enzyme MnATP-tetrahydrofolate the EPR line shapes are changed substantially. Spectra for the quaternary complexes exhibit narrow line widths, and the splitting patterns are characteristic of a slightly asymmetric electronic environment for the bound Mn(II). Addition of formate to the ADP quatenary complex induces a further significant narrowing of the EPR line widths, although in the absence of tetrahydrofolate, formate does not influence the EPR spectrum for the enzyme-MnADP species. Both Pi and nitrate cause changes in the EPR patterns for the higher complexes of the enzyme which involve both ADP and tetrahydololate. However, the Pi effect is not influenced by the presence of formate whereas the characteristic effect of nitrate is potentiated only when formate is present. EPR sectra for the thernary complex with the beta, gamma-methylene analog of ATP App(CH2)p differ significantly from spectra for the binary App(CH)p complex is not influenced by further additions of tetrahydrofolate and of tetrahydorfolate and formate. The failure of spectra for the App(CH)p complex to respond to additions of the other substrates for the reaction is in marked contrast to the behavior found for the natural nucleotide substrates and is tentatively attributed to the lack of a protein-mediated interaction between the nucleotide and tetrahydrofolate binding sites in the analog complex. The frequency dependence of solvent PRR in the presence of the various complexes allows an estimate of the correlation times for electron-nuclear dipolar interaction and thereby the extent of hydration of the bound Mn(II) among the various complexes.."} {"id": "PMID:166990", "title": "Reduced diphosphopyridine nucleotide peroxidase. Intermediates formed on reduction of the enzyme with dithionite or reduced diphosphopyridine nucleotide.", "content": "DPNH peroxidase is a flavin adenine dinucleotide-containing flavoprotein. Anaerobic titration of enzyme with dithionite has shown that the active site of the enzyme contains 2 mol of flavin and in addition 1 mol of a non-flavin electron acceptor that is tentatively identified as a disulfide group. Thus complete reduction of the enzyme requires 3 mol of dithionite per mole of active site. The first mole of dithionite reduces the non-flavin acceptor; complex formation between the reduced acceptor and one of the bound flavin molecules causes the formation of a long wavelength absorption band between 500 and 670 nm. The second mole of dithionite reduces the flavin that interacts with the reduced non-flavin group, and the long wavelength band disappears. The third mole of dithionite reduces the second mole of flavin. All groups are reoxidized in the presence of air. DPNH reacts with only two of the enzyme-bound electron acceptors. The first mole of DPNH reduces the non-flavin group to form an intermediate (I) that is almost identical with that formed by dithionite. The second mole of DPNH complexes with the second flavin of Intermediate I to form Intermediate II. This reaction causes a further absorbance increase in the long wavelength region; the tail of the absorption band now extends to 960 nm. The titration data (potassium phosphate, 0.05 M, pH 7.0) can be fitted with dissociation constants of 1 times 10-7 M for the formation of I, and 3 times 10-6 M for the conversion of I to II. In air, species II is oxidized to I; I is stable in air, but is oxidized stoichiometrically to oxidized enzyme by H2O2. Present evidence suggests that bound DPN-plus is responsible for the air stability of species I. Intermediate I, but not oxidized enzyme, reacts slowly with phenylmercuric acetate. This reaction causes loss of the air-stable intermediate and parallel loss in enzyme activity. The inactive enzyme cannot be reduced by DPNH to Species I; DPNH can, however, still react with the second flavin to form the autoxidizable complex. With other methods of enzyme inactivation there is also a direct correlation between residual enzyme activity and the ability of enzyme to form the air-stable intermediate. It is concluded that the air-stable intermediate is an important catalytic species.", "contents": "Reduced diphosphopyridine nucleotide peroxidase. Intermediates formed on reduction of the enzyme with dithionite or reduced diphosphopyridine nucleotide. DPNH peroxidase is a flavin adenine dinucleotide-containing flavoprotein. Anaerobic titration of enzyme with dithionite has shown that the active site of the enzyme contains 2 mol of flavin and in addition 1 mol of a non-flavin electron acceptor that is tentatively identified as a disulfide group. Thus complete reduction of the enzyme requires 3 mol of dithionite per mole of active site. The first mole of dithionite reduces the non-flavin acceptor; complex formation between the reduced acceptor and one of the bound flavin molecules causes the formation of a long wavelength absorption band between 500 and 670 nm. The second mole of dithionite reduces the flavin that interacts with the reduced non-flavin group, and the long wavelength band disappears. The third mole of dithionite reduces the second mole of flavin. All groups are reoxidized in the presence of air. DPNH reacts with only two of the enzyme-bound electron acceptors. The first mole of DPNH reduces the non-flavin group to form an intermediate (I) that is almost identical with that formed by dithionite. The second mole of DPNH complexes with the second flavin of Intermediate I to form Intermediate II. This reaction causes a further absorbance increase in the long wavelength region; the tail of the absorption band now extends to 960 nm. The titration data (potassium phosphate, 0.05 M, pH 7.0) can be fitted with dissociation constants of 1 times 10-7 M for the formation of I, and 3 times 10-6 M for the conversion of I to II. In air, species II is oxidized to I; I is stable in air, but is oxidized stoichiometrically to oxidized enzyme by H2O2. Present evidence suggests that bound DPN-plus is responsible for the air stability of species I. Intermediate I, but not oxidized enzyme, reacts slowly with phenylmercuric acetate. This reaction causes loss of the air-stable intermediate and parallel loss in enzyme activity. The inactive enzyme cannot be reduced by DPNH to Species I; DPNH can, however, still react with the second flavin to form the autoxidizable complex. With other methods of enzyme inactivation there is also a direct correlation between residual enzyme activity and the ability of enzyme to form the air-stable intermediate. It is concluded that the air-stable intermediate is an important catalytic species."} {"id": "PMID:166991", "title": "Hydrophobic binding sites on human interferon.", "content": "Human interferon binds to a omega-carboxpentyl-agarose column at low ionic strength (0.15 M NaCl) and is still retained when the ionic strength is raised (to 1.0 M NaCl). The binding can be reversed, however, by ethylene glycol, indicating a hydrophobic interaction. The binding of human interferon to omega-aminohexyl-agarose is weak, even at a low ionic strength, and is probably exclusively electrostatic. This disparate binding behavior may be caused by the presence of a positive charge, adjacent to the hydrophobic binding site, on human interferon. The interaction of human interferon with omega-carboxypentyl-agarose is quite selective, inasmuch as the majority of proteins present in interferon preparations pass through the column unretained. Hydrophobic chromatography of human interferon may thus be useful in its purification.", "contents": "Hydrophobic binding sites on human interferon. Human interferon binds to a omega-carboxpentyl-agarose column at low ionic strength (0.15 M NaCl) and is still retained when the ionic strength is raised (to 1.0 M NaCl). The binding can be reversed, however, by ethylene glycol, indicating a hydrophobic interaction. The binding of human interferon to omega-aminohexyl-agarose is weak, even at a low ionic strength, and is probably exclusively electrostatic. This disparate binding behavior may be caused by the presence of a positive charge, adjacent to the hydrophobic binding site, on human interferon. The interaction of human interferon with omega-carboxypentyl-agarose is quite selective, inasmuch as the majority of proteins present in interferon preparations pass through the column unretained. Hydrophobic chromatography of human interferon may thus be useful in its purification."} {"id": "PMID:166992", "title": "On the fidelity of DNA replication. Characterization of polynucleotides with errors in base-pairing synthesized by avian myeloblastosis virus deoxyribonucleic acid polymerase.", "content": "Polynucleotide templates were copied by avian myeloblastosis virus DNA polymerase (\"reverse transcriptase\") and the frequency and distribution of errors were determined. The error rate with [r(pA)2500-d(pT)12-18] template-initiator under a variety of conditions was approximately 1/600, i.e. one incorrect dCMP incorporated for 600 correct dTMP polymerized. Addition of the metal chelator o-phenanthroline to the reaction inhibited the incorporation of correct and incorrect nucleotides proportionately. The enzyme inhibited a pH optimum of 8.5 and the error rate remained constant over a range of pH (6.0 to 10.0). The rate of polymerization was greater at higher temperatures and approximately doubled for every 10 degrees increase. The error rate was constant at all temperatures. These results indicate that the purified avian myeloblastosis virus DNA polymerase synthesizes polydeoxynucleotides with an unusually large number of errors in base-pairing. Velocity sedimentation of the products of the reaction obtained at various times during the course of synthesis indicate that: (a) the entire length of the 14 S template was copied, and (b) the incorporation of the incorrect nucleotide did not terminate chain propagation. Isopyknic banding in neutral and alkaline cesium sulfate gradients showed that the noncomplementary nucleotides are incorporated into the polydeoxynucleotide product. Stepwise degradation and nearest neighbor analysis of the reaction product indicated that (a) the correct and incorrect nucleotides are present in phosphodiester linkages, (b) the errors are not concentrated at either termini; and (c) the errors are uniformly distributed throughout the newly synthesized polydeoxynucleotide.", "contents": "On the fidelity of DNA replication. Characterization of polynucleotides with errors in base-pairing synthesized by avian myeloblastosis virus deoxyribonucleic acid polymerase. Polynucleotide templates were copied by avian myeloblastosis virus DNA polymerase (\"reverse transcriptase\") and the frequency and distribution of errors were determined. The error rate with [r(pA)2500-d(pT)12-18] template-initiator under a variety of conditions was approximately 1/600, i.e. one incorrect dCMP incorporated for 600 correct dTMP polymerized. Addition of the metal chelator o-phenanthroline to the reaction inhibited the incorporation of correct and incorrect nucleotides proportionately. The enzyme inhibited a pH optimum of 8.5 and the error rate remained constant over a range of pH (6.0 to 10.0). The rate of polymerization was greater at higher temperatures and approximately doubled for every 10 degrees increase. The error rate was constant at all temperatures. These results indicate that the purified avian myeloblastosis virus DNA polymerase synthesizes polydeoxynucleotides with an unusually large number of errors in base-pairing. Velocity sedimentation of the products of the reaction obtained at various times during the course of synthesis indicate that: (a) the entire length of the 14 S template was copied, and (b) the incorporation of the incorrect nucleotide did not terminate chain propagation. Isopyknic banding in neutral and alkaline cesium sulfate gradients showed that the noncomplementary nucleotides are incorporated into the polydeoxynucleotide product. Stepwise degradation and nearest neighbor analysis of the reaction product indicated that (a) the correct and incorrect nucleotides are present in phosphodiester linkages, (b) the errors are not concentrated at either termini; and (c) the errors are uniformly distributed throughout the newly synthesized polydeoxynucleotide."} {"id": "PMID:166993", "title": "Carbamylphosphate synthetase from Salmonella typhimurium. Regulations, subunit composition, and function of the subunits.", "content": "Carbamylphosphate synthetase was purified to homogeneity from a derepressed strain of Salmonella typhimurium by a procedure based on affinity chromatography employing immobilized glutamine. The enzyme catalyzes the synthesis of carbamylphosphate from either ammonia or glutamine together with ATP and bicarbonate. The ATP saturation curve of either nitrogen donor is sigmoidal (n equals 1.5) but the affinity for ATP is higher with ammonia. In addition to the feedback inhibition by UMP and activation by ornithine which we previously reported (1), the activity was found to be stimulated by IMP and phosphoribosyl-1-pyrophosphate. Evidence from pool measurements in enteric bacteria by others suggests that of the latter two compounds only phosphoribosyl-1-pyrophosphate is physiologically significant. All effectors regulate enzyme activity by altering its affinity for ATP. Glutamine also modulates the affinity for ATP; it is increased as glutamine concentratiions decrease, an effect that could serve to insulate the cell against major changes in carbamylphosphate synthesis in response to fluctuations in concentration of glutamine. The molecular weight of the holoenzyme was estimated to be 150,000 by sucrose density gradient centrifugation in triethanolamine and Tris-acetate buffers in which the enzyme is a monomer. In the presence of ornithine in potassium phosphate buffer, the enzyme is an oligomer with a molecular weight of 580,000. This transition has been exploited as an alternate route of purifying the enzyme to homogeneity using successive sucrose density centrifugation. Polyacrylamide gel electrophoresis of the enzyme in the presence of sodium dodecyl sulfate shows that the enzyme consists of two unequal subunits with molecular weights of 110,000 and 45,000. The two subunits were separated by gel filtration in the presence of 1 M potassium thiocyanate, ATP, MgCl2, glutamine, NH4Cl, ornithine, and UMP. The heavy subunit catalyzes the synthesis of carbamylphosphate from ammonia but not glutamine. The ATP saturation curve for the separated heavy subunit is still sigmoidal (n equals 1.4 and So.5 equals 0.3 mM). The ammonia dependent activity of the heavy subunit is stimulated by the activators ornithine, IMP, and phosphoribosyl-1-pyrophosphate but is only marginally inhibited by high concentrations of UMP. The addition of the light subunit restored full ability to utilize glutamine as well as normal sensitivity to UMP. Purified subunits were used for in vitro complementation studies with strains carrying mutations in pyrA, the structural gene encoding carbamylphosphate synthetase. The results indicate that the pyrA region encodes both subunits and that the structural genes for the two polypeptides are linked. A deletion mutant lacking both subunits of carbamylphosphate synthetase also lacked any ability to synthetize carbamylphosphate from ammonia. Hence, unlike certain other bacteria, S. typhimurium does not possess a carbamate kinase.", "contents": "Carbamylphosphate synthetase from Salmonella typhimurium. Regulations, subunit composition, and function of the subunits. Carbamylphosphate synthetase was purified to homogeneity from a derepressed strain of Salmonella typhimurium by a procedure based on affinity chromatography employing immobilized glutamine. The enzyme catalyzes the synthesis of carbamylphosphate from either ammonia or glutamine together with ATP and bicarbonate. The ATP saturation curve of either nitrogen donor is sigmoidal (n equals 1.5) but the affinity for ATP is higher with ammonia. In addition to the feedback inhibition by UMP and activation by ornithine which we previously reported (1), the activity was found to be stimulated by IMP and phosphoribosyl-1-pyrophosphate. Evidence from pool measurements in enteric bacteria by others suggests that of the latter two compounds only phosphoribosyl-1-pyrophosphate is physiologically significant. All effectors regulate enzyme activity by altering its affinity for ATP. Glutamine also modulates the affinity for ATP; it is increased as glutamine concentratiions decrease, an effect that could serve to insulate the cell against major changes in carbamylphosphate synthesis in response to fluctuations in concentration of glutamine. The molecular weight of the holoenzyme was estimated to be 150,000 by sucrose density gradient centrifugation in triethanolamine and Tris-acetate buffers in which the enzyme is a monomer. In the presence of ornithine in potassium phosphate buffer, the enzyme is an oligomer with a molecular weight of 580,000. This transition has been exploited as an alternate route of purifying the enzyme to homogeneity using successive sucrose density centrifugation. Polyacrylamide gel electrophoresis of the enzyme in the presence of sodium dodecyl sulfate shows that the enzyme consists of two unequal subunits with molecular weights of 110,000 and 45,000. The two subunits were separated by gel filtration in the presence of 1 M potassium thiocyanate, ATP, MgCl2, glutamine, NH4Cl, ornithine, and UMP. The heavy subunit catalyzes the synthesis of carbamylphosphate from ammonia but not glutamine. The ATP saturation curve for the separated heavy subunit is still sigmoidal (n equals 1.4 and So.5 equals 0.3 mM). The ammonia dependent activity of the heavy subunit is stimulated by the activators ornithine, IMP, and phosphoribosyl-1-pyrophosphate but is only marginally inhibited by high concentrations of UMP. The addition of the light subunit restored full ability to utilize glutamine as well as normal sensitivity to UMP. Purified subunits were used for in vitro complementation studies with strains carrying mutations in pyrA, the structural gene encoding carbamylphosphate synthetase. The results indicate that the pyrA region encodes both subunits and that the structural genes for the two polypeptides are linked. A deletion mutant lacking both subunits of carbamylphosphate synthetase also lacked any ability to synthetize carbamylphosphate from ammonia. Hence, unlike certain other bacteria, S. typhimurium does not possess a carbamate kinase."} {"id": "PMID:166994", "title": "Characteristics of 5'-guanylyl imidodiphosphate-activated adenylate cyclase.", "content": "Characteristics of adenylate cyclase stimulation by the GTP analog 5'-guanyl imidodiphosphate Gpp(NH)p have been examined in intact frog erythrocytes, frog erythrocyte membranes, and solubilized canine myocardial preparations. Gpp(NH)p caused marked enzyme activation in the erythrocyte membranes and in solubilized myocardial preparations, but had much lesser effects in intact cells. Enzyme activation by Gpp(NH)p exhibited a definite lag period, requiring 10 to 15 min for complete activation at 37 degrees. Activation was essentially irreversible after a 5-hour dialysis sufficient to reduce the Gpp(NH)p levels below threshold for stimulation. Gpp(NH)p-\"activated\" enzyme differed from native enzyme in several respects, such as its greater temperature stability, and its insensitivity to further stimulation by other activators, such as catecholamine or fluoride. These differences suggest that the enzyme, once fully activated by Gpp(NH)p, may have undergone some modification that is not subject ot facile reversal.", "contents": "Characteristics of 5'-guanylyl imidodiphosphate-activated adenylate cyclase. Characteristics of adenylate cyclase stimulation by the GTP analog 5'-guanyl imidodiphosphate Gpp(NH)p have been examined in intact frog erythrocytes, frog erythrocyte membranes, and solubilized canine myocardial preparations. Gpp(NH)p caused marked enzyme activation in the erythrocyte membranes and in solubilized myocardial preparations, but had much lesser effects in intact cells. Enzyme activation by Gpp(NH)p exhibited a definite lag period, requiring 10 to 15 min for complete activation at 37 degrees. Activation was essentially irreversible after a 5-hour dialysis sufficient to reduce the Gpp(NH)p levels below threshold for stimulation. Gpp(NH)p-\"activated\" enzyme differed from native enzyme in several respects, such as its greater temperature stability, and its insensitivity to further stimulation by other activators, such as catecholamine or fluoride. These differences suggest that the enzyme, once fully activated by Gpp(NH)p, may have undergone some modification that is not subject ot facile reversal."} {"id": "PMID:166995", "title": "Purification and regulatory properties of chicken heart prostaglandin E 9-ketoreductase.", "content": "Prostaglandin E 9-ketoreductase was purified from chicken heart by ammonium sulfate fractionation, and DEAE-Sephadex, hydroxylapatite and phosphocellulose chromatography. Two peaks of activity were resolved during the phosphocellulose chromatographic step. Both peaks were stimulated by a substance that was not bound to the phosphocellulose column. This stimulatory substance was destroyed by treatment with phosphodiesterase and 0.1 M NaOH. It was heat-stable (100 degrees, 2 min), nondialyzable, and resistant to treatment with pronase, ribonuclease, and deoxyribonuclease; but it was dialyzable after heating or digestion with pronase. Sodium pyrophosphate also enhanced the activities of the prostaglandin E 9-ketoreductases as did angiotensin I; but not angiotensin II. In the presence of 3':5'-cyclic AMP, AMP, or several other ribonucleotides, the enhancing effects of the natural stimulatory substance, sodium pyrophosphate or angiotensin I were blocked, but these ribonucleotides themselves had little effect on the enzymes activity. The substrate specificities of the two prostaglandin E 9-ketoreductases were also studied. Both the 9-keto group and the 15-keto group of 15-ketoprostaglandin F2 alpha could be converted to the corresponding hydroxyl group; the 15-keto group was reduced faster than the 9-keto group. Prostaglandin D2, a prostaglandin with a 9-hydroxyl and an 11-keto group, could not be converted to prostaglandin F2 alpha nor could cyclohexanone be converted to cyclohexanol by the prostaglandin E 9-ketoreductase.", "contents": "Purification and regulatory properties of chicken heart prostaglandin E 9-ketoreductase. Prostaglandin E 9-ketoreductase was purified from chicken heart by ammonium sulfate fractionation, and DEAE-Sephadex, hydroxylapatite and phosphocellulose chromatography. Two peaks of activity were resolved during the phosphocellulose chromatographic step. Both peaks were stimulated by a substance that was not bound to the phosphocellulose column. This stimulatory substance was destroyed by treatment with phosphodiesterase and 0.1 M NaOH. It was heat-stable (100 degrees, 2 min), nondialyzable, and resistant to treatment with pronase, ribonuclease, and deoxyribonuclease; but it was dialyzable after heating or digestion with pronase. Sodium pyrophosphate also enhanced the activities of the prostaglandin E 9-ketoreductases as did angiotensin I; but not angiotensin II. In the presence of 3':5'-cyclic AMP, AMP, or several other ribonucleotides, the enhancing effects of the natural stimulatory substance, sodium pyrophosphate or angiotensin I were blocked, but these ribonucleotides themselves had little effect on the enzymes activity. The substrate specificities of the two prostaglandin E 9-ketoreductases were also studied. Both the 9-keto group and the 15-keto group of 15-ketoprostaglandin F2 alpha could be converted to the corresponding hydroxyl group; the 15-keto group was reduced faster than the 9-keto group. Prostaglandin D2, a prostaglandin with a 9-hydroxyl and an 11-keto group, could not be converted to prostaglandin F2 alpha nor could cyclohexanone be converted to cyclohexanol by the prostaglandin E 9-ketoreductase."} {"id": "PMID:166996", "title": "The role of Ca-2+ and cyclic adenosine 3':5'-monophosphate in insulin release induced in vitro by the divalent cation ionophore A23187.", "content": "Insulin release from isolated perifused pancreatic islets was stimulated by the divalent ionophore A23187 in the absence of exogenous glucose. In addition, A23187 produced a 2-fold elevation of cyclic adenosine 3':5'-monophosphate (cAMP) levels in isolated perifused islets. The elevation of cAMP levels coincided with peak insulin release. Ionophore-induced insulin release was unaffected by pretreatment of the islets with theophylline (5 mM). Stimulation of insulin release produced by the ionophore occurred either in the presence or absence of extracellular Ca-2+; however, cAMP accumulation required the presence of extracellular Ca-2+. The ionophore (10 muM) had no effect on adenylate cyclase activity of homogenates of isolated islets. The results of this study are interpreted as indicating that intracellular Ca-2+ has an essential role in the insulin releasing mechanism, whereas the cAMP system has a modulatory effect on this process.", "contents": "The role of Ca-2+ and cyclic adenosine 3':5'-monophosphate in insulin release induced in vitro by the divalent cation ionophore A23187. Insulin release from isolated perifused pancreatic islets was stimulated by the divalent ionophore A23187 in the absence of exogenous glucose. In addition, A23187 produced a 2-fold elevation of cyclic adenosine 3':5'-monophosphate (cAMP) levels in isolated perifused islets. The elevation of cAMP levels coincided with peak insulin release. Ionophore-induced insulin release was unaffected by pretreatment of the islets with theophylline (5 mM). Stimulation of insulin release produced by the ionophore occurred either in the presence or absence of extracellular Ca-2+; however, cAMP accumulation required the presence of extracellular Ca-2+. The ionophore (10 muM) had no effect on adenylate cyclase activity of homogenates of isolated islets. The results of this study are interpreted as indicating that intracellular Ca-2+ has an essential role in the insulin releasing mechanism, whereas the cAMP system has a modulatory effect on this process."} {"id": "PMID:166997", "title": "The kinetics of glucocorticoid binding to the soluble specific binding protein of mouse fibroblasts.", "content": "The kinetics of binding of glucocorticoids to the soluble, specific binding protein of mouse fibroblasts has been examined. The rate at which both potent and weak glucocorticoids achieve binding equilibrium is very slow. Second order rate constants of association range from 3 times 10-5 M- minus 1 min- minus 1 for cortisol to 6.7 times 10-5 M- minus 1 min- minus 1 for triamcinolone acetonide. Studies of the rates of binding at high steroid concentrations suggest that the slow rate of binding may be explained by a two-step mechanism. Active glucocorticoids, regardless of their potency, bind initially in a rapid manner to form a weak complex with the binding protein. The dissociation constant for the weak binding reaction is 0.87 times 10- minus 7 M for triamcinolone acetonide and 2.4 times 10- minus 7 M for cortisol. The weak binding complex becomes converted slowly to a tight complex. The first order rate constants for this conversion and the rate constants of dissociation from the tight complex have been determined for cortisol, dexamethasone and triamcinolone acetonide. The binding affinity of steroids of different biological potency is correlated with their rate of dissociation from this second tight binding state.", "contents": "The kinetics of glucocorticoid binding to the soluble specific binding protein of mouse fibroblasts. The kinetics of binding of glucocorticoids to the soluble, specific binding protein of mouse fibroblasts has been examined. The rate at which both potent and weak glucocorticoids achieve binding equilibrium is very slow. Second order rate constants of association range from 3 times 10-5 M- minus 1 min- minus 1 for cortisol to 6.7 times 10-5 M- minus 1 min- minus 1 for triamcinolone acetonide. Studies of the rates of binding at high steroid concentrations suggest that the slow rate of binding may be explained by a two-step mechanism. Active glucocorticoids, regardless of their potency, bind initially in a rapid manner to form a weak complex with the binding protein. The dissociation constant for the weak binding reaction is 0.87 times 10- minus 7 M for triamcinolone acetonide and 2.4 times 10- minus 7 M for cortisol. The weak binding complex becomes converted slowly to a tight complex. The first order rate constants for this conversion and the rate constants of dissociation from the tight complex have been determined for cortisol, dexamethasone and triamcinolone acetonide. The binding affinity of steroids of different biological potency is correlated with their rate of dissociation from this second tight binding state."} {"id": "PMID:166998", "title": "Chemical synthesis and sequence studies of deoxyribooligonucleotides which constitute the duplex sequence of the lactose operator of Escherichia coli.", "content": "We have synthesized the deoxyribooligonucleotide fragments, constituting the sequence of the lac operator of Escherichia coli. Two of these fragments, d(pApApTpTpGpTpTpApT) (nonamer) and d(pApApTpTpGpTpGpApG) (nonamer), corresponding to the 5' termini of lac operator have been synthesized by the phosphodiester method. The remaining four fragments, d(ApCpApApTpT) (hexamer), d(ApTpApApCpApApTpT) (nonamer), d(ApApTpTpGpTpGpApGpCpGpG) (dodecamer), and d(ApApTpTpGpTpTpApTpCpCpGpCpTpC) (pentadecamer), have been synthesized by an improved phosphotriester method. All of the compounds were first characterized by venom and spleen phosphodiesterase digestion to obtain their base composition. The sequence of these oligonucleotides was fully confirmed by the characteristic mobility shifts of their partial venom phosphodiesterase digestion products on two-dimensional homochromatography. A comparative study of the two methods for the synthesis of oligonucleotides has revealed that the phosphotriester method is more convenient than the phosphodiester method because of higher yields and ease of handling large scale preparations.", "contents": "Chemical synthesis and sequence studies of deoxyribooligonucleotides which constitute the duplex sequence of the lactose operator of Escherichia coli. We have synthesized the deoxyribooligonucleotide fragments, constituting the sequence of the lac operator of Escherichia coli. Two of these fragments, d(pApApTpTpGpTpTpApT) (nonamer) and d(pApApTpTpGpTpGpApG) (nonamer), corresponding to the 5' termini of lac operator have been synthesized by the phosphodiester method. The remaining four fragments, d(ApCpApApTpT) (hexamer), d(ApTpApApCpApApTpT) (nonamer), d(ApApTpTpGpTpGpApGpCpGpG) (dodecamer), and d(ApApTpTpGpTpTpApTpCpCpGpCpTpC) (pentadecamer), have been synthesized by an improved phosphotriester method. All of the compounds were first characterized by venom and spleen phosphodiesterase digestion to obtain their base composition. The sequence of these oligonucleotides was fully confirmed by the characteristic mobility shifts of their partial venom phosphodiesterase digestion products on two-dimensional homochromatography. A comparative study of the two methods for the synthesis of oligonucleotides has revealed that the phosphotriester method is more convenient than the phosphodiester method because of higher yields and ease of handling large scale preparations."} {"id": "PMID:166999", "title": "DNA sequence analysis. Terminal sequences of bacteriophage phi80.", "content": "Sequences of the cohesive ends and the 3'-terminal regions of phi80 DNA have been determined. Sequences of the cohesive ends were obtained through the use of two standard methods. The first method involved the incorporation of all four labeled deoxyribonucleotides into the phi80 cohesive ends using DNA polymerase I. The DNA was then partially digested with micrococcal nuclease or pancreatic DNase. The products were separated by two-dimensional electrophoresis and characterized by composition, 3'-terminal, and nearest neighbor analyses. The second method involved partial incorporation using one, two, or three labeled deoxyribonucleotides followed by similar analyses. Sequences of the double-stranded regions adjacent to the cohesive ends were determined by three new methods. These methods were: (a) the DNA was specifically labeled at the 3' terminus and then partially degraded. Labeled oligonucleotide products were sequenced by their mobilities on various separation systems. (b) The cohesive ends were enlarged by limited degradation with exonuclease III. After this treatment, the DNA was partially repaired with labeled nucleotides, digested, and the products were analyzed. (c) A synthetic ologonucleotide primer was bound to phi80 DNA which had been repaired with DNA polymerase I, and then partially digested with lambda-exonuclease. The primer was extended into the region of interest by partial repair with labeled nucleotides. The extended primer was isolated and analyzed.", "contents": "DNA sequence analysis. Terminal sequences of bacteriophage phi80. Sequences of the cohesive ends and the 3'-terminal regions of phi80 DNA have been determined. Sequences of the cohesive ends were obtained through the use of two standard methods. The first method involved the incorporation of all four labeled deoxyribonucleotides into the phi80 cohesive ends using DNA polymerase I. The DNA was then partially digested with micrococcal nuclease or pancreatic DNase. The products were separated by two-dimensional electrophoresis and characterized by composition, 3'-terminal, and nearest neighbor analyses. The second method involved partial incorporation using one, two, or three labeled deoxyribonucleotides followed by similar analyses. Sequences of the double-stranded regions adjacent to the cohesive ends were determined by three new methods. These methods were: (a) the DNA was specifically labeled at the 3' terminus and then partially degraded. Labeled oligonucleotide products were sequenced by their mobilities on various separation systems. (b) The cohesive ends were enlarged by limited degradation with exonuclease III. After this treatment, the DNA was partially repaired with labeled nucleotides, digested, and the products were analyzed. (c) A synthetic ologonucleotide primer was bound to phi80 DNA which had been repaired with DNA polymerase I, and then partially digested with lambda-exonuclease. The primer was extended into the region of interest by partial repair with labeled nucleotides. The extended primer was isolated and analyzed."} {"id": "PMID:167000", "title": "Cytochrome P-450 of adrenal mitochondria. Spin states as detected by difference spectroscopy.", "content": "Adrenal mitochondrial cytochrome P-450 which functions in cholesterol side chain cleavage (P-450scc) exhibited type I (lambdamax 385, lambdamin 420 nm) and inverse type I (lambdamin 385, lambdamax 420 nm) difference spectra with several steroids. The magnitude and type of response were dependent on the particular steroid and on the extent to which cholesterol was bound to the cytochrome in the intact mitochondrion. the inverse type I difference spectrum induced by 3beta-hydroxy-pregn-5-ene-20-one (pregnenolone) was dependent on the proportion of high spin cholesterol-cytochrome P-450scc complexes. With rat adrenal mitochondria cholest-5-ene-3beta, 20alpha-diol (20alpha-hydroxycholesterol) invariably induced a smaller inverse type I response and, under conditions where cytochrome P-450scc was nearly free of cholesterol, even produced a small type I response. Two distinct steroid binding sites on cytochrome P-450scc were detected by, respectively, the slow type I response to cholest-5-ene-3beta, 25-diol (25-hydroxycholesterol) and the rapid type I response to a subsequent addition of cholest-5-ene-3beta, 20alpha, 22 R-triol (20alpha, 22R-dihydroxycholesterol). The relative proportions of the spectral responses to these steroids were dependent on the previous extent of adrenal activation by adrenocorticotropic hormone (ACTH), because this stimulatory process altered the combination of mitochondrial cholesterol with cytochrome P-450scc. It is proposed that the two steroid binding sites on cytochrome P-450scc interact with steroids in the following way: site I binds cholesterol, 25-hydroxycholesterol, and 20alpha, 22R-dihydroxycholesterol with formation of a partially high spin cytochrome; site II binds both pregnenolone and 20alpha-OH cholesterol resulting in a low spin cytochrome. Interactions between sites I and II are not competitive, and occupancy of site II ensures a low spin state irrespective of the occupancy of site I. A second mode of interaction by 20alpha, 22R-dihydroxycholesterol stabilizes a high spin cytochrome and is competitive with site II binding by 20alpha-hydroxycholesterol or pregnenolone. Formation of a maximally high spin cytochrome follows occupancy by 20alpha, 22R-dihydroxycholesterol at both sites.", "contents": "Cytochrome P-450 of adrenal mitochondria. Spin states as detected by difference spectroscopy. Adrenal mitochondrial cytochrome P-450 which functions in cholesterol side chain cleavage (P-450scc) exhibited type I (lambdamax 385, lambdamin 420 nm) and inverse type I (lambdamin 385, lambdamax 420 nm) difference spectra with several steroids. The magnitude and type of response were dependent on the particular steroid and on the extent to which cholesterol was bound to the cytochrome in the intact mitochondrion. the inverse type I difference spectrum induced by 3beta-hydroxy-pregn-5-ene-20-one (pregnenolone) was dependent on the proportion of high spin cholesterol-cytochrome P-450scc complexes. With rat adrenal mitochondria cholest-5-ene-3beta, 20alpha-diol (20alpha-hydroxycholesterol) invariably induced a smaller inverse type I response and, under conditions where cytochrome P-450scc was nearly free of cholesterol, even produced a small type I response. Two distinct steroid binding sites on cytochrome P-450scc were detected by, respectively, the slow type I response to cholest-5-ene-3beta, 25-diol (25-hydroxycholesterol) and the rapid type I response to a subsequent addition of cholest-5-ene-3beta, 20alpha, 22 R-triol (20alpha, 22R-dihydroxycholesterol). The relative proportions of the spectral responses to these steroids were dependent on the previous extent of adrenal activation by adrenocorticotropic hormone (ACTH), because this stimulatory process altered the combination of mitochondrial cholesterol with cytochrome P-450scc. It is proposed that the two steroid binding sites on cytochrome P-450scc interact with steroids in the following way: site I binds cholesterol, 25-hydroxycholesterol, and 20alpha, 22R-dihydroxycholesterol with formation of a partially high spin cytochrome; site II binds both pregnenolone and 20alpha-OH cholesterol resulting in a low spin cytochrome. Interactions between sites I and II are not competitive, and occupancy of site II ensures a low spin state irrespective of the occupancy of site I. A second mode of interaction by 20alpha, 22R-dihydroxycholesterol stabilizes a high spin cytochrome and is competitive with site II binding by 20alpha-hydroxycholesterol or pregnenolone. Formation of a maximally high spin cytochrome follows occupancy by 20alpha, 22R-dihydroxycholesterol at both sites."} {"id": "PMID:167001", "title": "Cytochrome P-450 of adrenal mitochondria. In vitro and in vivo changes in spin states.", "content": "Steroid-induced difference spectra have been used to examine the combination of cholesterol with adrenal mitochondrial cytochrome P-450 which participates in cholesterol side chain cleavage (P-450scc) and the depletion of cholesterol from the cytochrome which results from turnover of the enzyme system. Type I difference spectra-induced by cholest-5-ene-3beta, 25-diol (25-hydroxycholesterol) and cholest-5-ene-3beta, 20 alpha, 22R-triol (20alpha, 22R dihydroxycholesterol) have been used to quantitate binding of cholesterol to two sites (I and II) on cytochrome P-450scc. The action of adrenocorticotropic hormone (ACTH) in vivo and the action of calcium or phosphate ions on isolated mitochondria stimulate the combination of cholesterol with site I but not site II. Cholesterol derived from lecithin-cholesterol micelles, however, binds to both sites. Malate-induced cholesterol depletion occurred at a comparable rate to the transfer of cholesterol from lecithin-cholesterol micelles. However, a residual proportion of cholesterol-cytochrome P-450scc complexes remained, even after 10 min of exposure to malate, and was of similar magnitude in mitochondria from both cycloheximide-treated and stressed rats. It is suggested that this reflects a less reactive form of cholesterol-cytochrome complex. Steroid-induced difference spectra indicate that sites I and II on cytochrome P-450scc are similarly depleted after metabolism of mitochondrial cholesterol in vitro and after inhibition of the action of ACTH in vivo. Anaerobiosis of adrenal cells after excision of the accumulation of cholesterol at cytochrome P-450cc. When anaerobiosis was prevented, cytochrome P-450scc in the freshly isolated mitochondria was apparently essentially free of complexed cholesterol, irrespective of the extent of ACTH action. For 30 min after suspension of the mitochondria in 0.25 M sucrose at 4 degrees, cholesterol combines with cytochrome P-450scc. The extent of this process was not affected by the presence of cycloheximide during ether stress treatment of the rats. It is concluded that there are at least two pools of mitochondrial cholesterol with access to cytochrome P-450scc but that ACTH stimulates only the pool which most readily interacts with the cytochrome.", "contents": "Cytochrome P-450 of adrenal mitochondria. In vitro and in vivo changes in spin states. Steroid-induced difference spectra have been used to examine the combination of cholesterol with adrenal mitochondrial cytochrome P-450 which participates in cholesterol side chain cleavage (P-450scc) and the depletion of cholesterol from the cytochrome which results from turnover of the enzyme system. Type I difference spectra-induced by cholest-5-ene-3beta, 25-diol (25-hydroxycholesterol) and cholest-5-ene-3beta, 20 alpha, 22R-triol (20alpha, 22R dihydroxycholesterol) have been used to quantitate binding of cholesterol to two sites (I and II) on cytochrome P-450scc. The action of adrenocorticotropic hormone (ACTH) in vivo and the action of calcium or phosphate ions on isolated mitochondria stimulate the combination of cholesterol with site I but not site II. Cholesterol derived from lecithin-cholesterol micelles, however, binds to both sites. Malate-induced cholesterol depletion occurred at a comparable rate to the transfer of cholesterol from lecithin-cholesterol micelles. However, a residual proportion of cholesterol-cytochrome P-450scc complexes remained, even after 10 min of exposure to malate, and was of similar magnitude in mitochondria from both cycloheximide-treated and stressed rats. It is suggested that this reflects a less reactive form of cholesterol-cytochrome complex. Steroid-induced difference spectra indicate that sites I and II on cytochrome P-450scc are similarly depleted after metabolism of mitochondrial cholesterol in vitro and after inhibition of the action of ACTH in vivo. Anaerobiosis of adrenal cells after excision of the accumulation of cholesterol at cytochrome P-450cc. When anaerobiosis was prevented, cytochrome P-450scc in the freshly isolated mitochondria was apparently essentially free of complexed cholesterol, irrespective of the extent of ACTH action. For 30 min after suspension of the mitochondria in 0.25 M sucrose at 4 degrees, cholesterol combines with cytochrome P-450scc. The extent of this process was not affected by the presence of cycloheximide during ether stress treatment of the rats. It is concluded that there are at least two pools of mitochondrial cholesterol with access to cytochrome P-450scc but that ACTH stimulates only the pool which most readily interacts with the cytochrome."} {"id": "PMID:167002", "title": "Insulin binding to liver plasm membranes in the obese hyperglycemic (ob/ob) mouse. Demonstration of a decreased number of functionally normal receptors.", "content": "In previous studies, the insulin resistance of the obese hyperglycemic mouse (ob/ob) was found to be associated with decreased insulin binding to liver, fat, and lymphocytes. The present study demonstrates that the insulin receptors in the liver membranes of the ob/ob mouse are decreased in number, but are indistinguishable from normal by other criteria including affinity, kinetics of association and dissociation, temperature dependence of binding, and biological specificity of the binding reaction. The receptor in liver membranes of the ob/ob mouse is also indistinguishable with respect to insulin receptor site-site interactions. Degradation of both insulin and of receptor sites was studied and did not account for differences observed in binding. We conclude that the insulin receptor from the ob/ob mouse is a functionally normal receptor and that its presence in diminished number accounts for the observed decrease in insulin binding to liver plasma membranes.", "contents": "Insulin binding to liver plasm membranes in the obese hyperglycemic (ob/ob) mouse. Demonstration of a decreased number of functionally normal receptors. In previous studies, the insulin resistance of the obese hyperglycemic mouse (ob/ob) was found to be associated with decreased insulin binding to liver, fat, and lymphocytes. The present study demonstrates that the insulin receptors in the liver membranes of the ob/ob mouse are decreased in number, but are indistinguishable from normal by other criteria including affinity, kinetics of association and dissociation, temperature dependence of binding, and biological specificity of the binding reaction. The receptor in liver membranes of the ob/ob mouse is also indistinguishable with respect to insulin receptor site-site interactions. Degradation of both insulin and of receptor sites was studied and did not account for differences observed in binding. We conclude that the insulin receptor from the ob/ob mouse is a functionally normal receptor and that its presence in diminished number accounts for the observed decrease in insulin binding to liver plasma membranes."} {"id": "PMID:167003", "title": "The role of calcium in regulation of cyclic nucleotide content in human umbilical artery.", "content": "In term gestational human umbilical artery segments incubated in room air at 37 degrees, histamine, acetylcholine, bradykinin, K+, and serotonin (agonists that cause contraction) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering the content of adenosine 3':5'-monosphophate (cAMP); prostaglandin E1 (PGE1), which relaxes the artery, causes cAMP accumulation without affecting the cGMP content (Clyman, R. I., Sandler, J.A., Manganiello, V.C., and Vaughan, M. (1975) J. Clin. Invest., in press). It has been postulated that Ca-2+ is important in the regulation of cyclic nucleotides in other tissues. In the umbilical artery the control of cAMP content by PGE1 was independent of Ca-2+. After incubation in Ca-2+-free medium, the c GMP contentof the artery segments was decreased by 50% and was unaffected by histamine, acetylcholine, bradykinin, and K+. Readdition of Ca-2+ (2.7 mM) or Sr-2+ (3.6 mM) to the medium partially restored the basal cGMP content and the agonist effects on the cGMP content. However, Sr-2+ was not as effective as Ca-2+ in this regard. Ionophores A23187 and X537A (agents that facilitate Ca-2+ movement through membranes) mimicked the effects of these Ca-2+-dependent agonists on cGMP content. Incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (0.1 mM) increased both the basal content of cGMP and the histamine-induced accumulation 3-fold. This effect was dependent on the presence of Ca-2+ also. Accumulation of cGMP induced by serotonin, on the other hand, was not diminished in Ca-2+-depleted arteries and, in fact, seemed to be inhibited by 2.7 mM Ca-2+. These observations are consistent with the existence in the umbilical artery of two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca-2+.", "contents": "The role of calcium in regulation of cyclic nucleotide content in human umbilical artery. In term gestational human umbilical artery segments incubated in room air at 37 degrees, histamine, acetylcholine, bradykinin, K+, and serotonin (agonists that cause contraction) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering the content of adenosine 3':5'-monosphophate (cAMP); prostaglandin E1 (PGE1), which relaxes the artery, causes cAMP accumulation without affecting the cGMP content (Clyman, R. I., Sandler, J.A., Manganiello, V.C., and Vaughan, M. (1975) J. Clin. Invest., in press). It has been postulated that Ca-2+ is important in the regulation of cyclic nucleotides in other tissues. In the umbilical artery the control of cAMP content by PGE1 was independent of Ca-2+. After incubation in Ca-2+-free medium, the c GMP contentof the artery segments was decreased by 50% and was unaffected by histamine, acetylcholine, bradykinin, and K+. Readdition of Ca-2+ (2.7 mM) or Sr-2+ (3.6 mM) to the medium partially restored the basal cGMP content and the agonist effects on the cGMP content. However, Sr-2+ was not as effective as Ca-2+ in this regard. Ionophores A23187 and X537A (agents that facilitate Ca-2+ movement through membranes) mimicked the effects of these Ca-2+-dependent agonists on cGMP content. Incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (0.1 mM) increased both the basal content of cGMP and the histamine-induced accumulation 3-fold. This effect was dependent on the presence of Ca-2+ also. Accumulation of cGMP induced by serotonin, on the other hand, was not diminished in Ca-2+-depleted arteries and, in fact, seemed to be inhibited by 2.7 mM Ca-2+. These observations are consistent with the existence in the umbilical artery of two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca-2+."} {"id": "PMID:167004", "title": "The cyclic adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum. Binding characteristics of aggregation-competent cells and variation of binding levels during the life cycle.", "content": "Both cyclic guanosine 3':5'-monophosphate and dithiothreitol stimulate binding of cyclic adenosine 3':5'-monophosphate (cAMP) to aggregation-competent amoebae. Both compounds appear to function solely by preventing the hydrolysis of cAMP by the cell-bound phosphodiesterase. The dissociation constant for binding of cAMP is 36 nM. Both cAMP binding and membrane-bound phosphodiesterase activities increase dramatically as cells develop aggregation competence, reach a maximum at about 11 hours, and remain at high levels for up to 48 hours if cells are maintained in shaken suspension. When amoebae are allowed to aggregate and develop naturally, binding of cAMP increases during aggregation, decreases during tip formation, and disappears during culmination. Phosphodiesterase activity parallels binding activity except that the decreased level after tip formation is retained throughout culmination. Two N-6-modified cAMP derivatives compete with cAMP for binding sites. One derivative is fluorescent (1,N-6-etheno-cAMP); the other is photolyzable [N-6(ethyl-2-diazomalonyl)cAMP]. This result opens the possibilities of using fluorescence quenching for assay of in vitro binding and of affinity labeling of binding sites. Competition by the derivatives is only partial, indicating possible heterogeneity of binding sites. Both compounds inhibit hydrolysis of cAMP by the membrane-bound phosphodiesterase.", "contents": "The cyclic adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum. Binding characteristics of aggregation-competent cells and variation of binding levels during the life cycle. Both cyclic guanosine 3':5'-monophosphate and dithiothreitol stimulate binding of cyclic adenosine 3':5'-monophosphate (cAMP) to aggregation-competent amoebae. Both compounds appear to function solely by preventing the hydrolysis of cAMP by the cell-bound phosphodiesterase. The dissociation constant for binding of cAMP is 36 nM. Both cAMP binding and membrane-bound phosphodiesterase activities increase dramatically as cells develop aggregation competence, reach a maximum at about 11 hours, and remain at high levels for up to 48 hours if cells are maintained in shaken suspension. When amoebae are allowed to aggregate and develop naturally, binding of cAMP increases during aggregation, decreases during tip formation, and disappears during culmination. Phosphodiesterase activity parallels binding activity except that the decreased level after tip formation is retained throughout culmination. Two N-6-modified cAMP derivatives compete with cAMP for binding sites. One derivative is fluorescent (1,N-6-etheno-cAMP); the other is photolyzable [N-6(ethyl-2-diazomalonyl)cAMP]. This result opens the possibilities of using fluorescence quenching for assay of in vitro binding and of affinity labeling of binding sites. Competition by the derivatives is only partial, indicating possible heterogeneity of binding sites. Both compounds inhibit hydrolysis of cAMP by the membrane-bound phosphodiesterase."} {"id": "PMID:167005", "title": "Preparation and characterization of liver cells made permeable to macromolecules by treatment with toluene.", "content": "Isolated individual liver cells were made permeable to charged molecules and macromolecules by treatment with toluene, and the properties of such cells were examined in detail. The optimal conditions of toluene treatment, as determined by assay of aminoacyl-tRNA synthetase activities, was 7 to 9% toluene for 2 min at 0 degrees. Conditions are also described for maintaining the treated cells for periods up to 1 hour. Toluene treatment was found to be as efficient as various disruptive methods for making internal enzymes accessible to exogenous substrates, and this was true for enzymes in the cytosol, membrane, or organelle fractions. Electron microscopic and biochemical examination of toluen-treated cells indicated that they were relatively intact and lost only small amounts of cellular constituents to the suspension medium. The data in this paper suggest that toluene treatment of individual cells might prove useful for studies of macromolecular synthesis in liver;", "contents": "Preparation and characterization of liver cells made permeable to macromolecules by treatment with toluene. Isolated individual liver cells were made permeable to charged molecules and macromolecules by treatment with toluene, and the properties of such cells were examined in detail. The optimal conditions of toluene treatment, as determined by assay of aminoacyl-tRNA synthetase activities, was 7 to 9% toluene for 2 min at 0 degrees. Conditions are also described for maintaining the treated cells for periods up to 1 hour. Toluene treatment was found to be as efficient as various disruptive methods for making internal enzymes accessible to exogenous substrates, and this was true for enzymes in the cytosol, membrane, or organelle fractions. Electron microscopic and biochemical examination of toluen-treated cells indicated that they were relatively intact and lost only small amounts of cellular constituents to the suspension medium. The data in this paper suggest that toluene treatment of individual cells might prove useful for studies of macromolecular synthesis in liver;"} {"id": "PMID:167006", "title": "Characterization of gastric mucosal membranes. VIII. The localization of peptides by iodination and phosphorylation.", "content": "Two fractions of gastric mucosal membranes obtained by Ficoll-sucrose density gradient centrifugation were studied by a variety of techniques to localize the polypeptides. Gel electrophoresis showed the presence of five major polypeptides and several minor ones. Only one of these, 82,000 daltons, was available for iodination in the intact tissue. The two membrane fractions differed in their accessibility to peroxidase. The denser fraction showed two major defined iodination peaks at 82,000 and 102,000 daltons. Freeze-thawing and iodinating with 131-I produced additional labeling of peaks as well as relabeling the 82,000-dalton component, showing it was accessible from both sides of the membrane. The two major components were also sensitive to cross-linking, the 102,000 polypeptide being especially sensitive to --SH oxidation. Proteolysis with trypsin removed both components in the denser membrane fraction, in addition to inhibiting the K+-ATPase and K+-p-nitrophenylphosphatase of that fraction. Phosphorylation with [gamma-32-P]ATP labeled the 102,000-dalton component and K+, HCO3- minus and p-nitrophenylphosphate reduced the level of labeling. Hence the 102,000 region contains a subunit of the ATPase, is readily iodinated in inside-out vesicles, and is the most available for interpeptide S--S cross-linking.", "contents": "Characterization of gastric mucosal membranes. VIII. The localization of peptides by iodination and phosphorylation. Two fractions of gastric mucosal membranes obtained by Ficoll-sucrose density gradient centrifugation were studied by a variety of techniques to localize the polypeptides. Gel electrophoresis showed the presence of five major polypeptides and several minor ones. Only one of these, 82,000 daltons, was available for iodination in the intact tissue. The two membrane fractions differed in their accessibility to peroxidase. The denser fraction showed two major defined iodination peaks at 82,000 and 102,000 daltons. Freeze-thawing and iodinating with 131-I produced additional labeling of peaks as well as relabeling the 82,000-dalton component, showing it was accessible from both sides of the membrane. The two major components were also sensitive to cross-linking, the 102,000 polypeptide being especially sensitive to --SH oxidation. Proteolysis with trypsin removed both components in the denser membrane fraction, in addition to inhibiting the K+-ATPase and K+-p-nitrophenylphosphatase of that fraction. Phosphorylation with [gamma-32-P]ATP labeled the 102,000-dalton component and K+, HCO3- minus and p-nitrophenylphosphate reduced the level of labeling. Hence the 102,000 region contains a subunit of the ATPase, is readily iodinated in inside-out vesicles, and is the most available for interpeptide S--S cross-linking."} {"id": "PMID:167007", "title": "Oligo(A) not coded by DNA generating 3'-terminal heterogeneity in a lambda phage RNA.", "content": "An RNA species from Escherichia coli infected with phage lambda was purified by hybridization to lambda 1-strand DNA and shown to have variable length. This variability was due to a variable number of adenylate residues attached to the 3' end of the molecule. Pancreatic RNase treatment of the RNA-DNA hybrid removed the 3'-terminal adenylate residues, generating a homogeneous RNA molecule terminating with -Up. The results indicate the presence of adenylate residues not coded by the DNA template at the terminus of this transcript from intact cells.", "contents": "Oligo(A) not coded by DNA generating 3'-terminal heterogeneity in a lambda phage RNA. An RNA species from Escherichia coli infected with phage lambda was purified by hybridization to lambda 1-strand DNA and shown to have variable length. This variability was due to a variable number of adenylate residues attached to the 3' end of the molecule. Pancreatic RNase treatment of the RNA-DNA hybrid removed the 3'-terminal adenylate residues, generating a homogeneous RNA molecule terminating with -Up. The results indicate the presence of adenylate residues not coded by the DNA template at the terminus of this transcript from intact cells."} {"id": "PMID:167008", "title": "Gonadotropin receptors. Solubilization and purification by affinity chromatography.", "content": "Specific gonadotropin receptors of the rat testis were purified 15,000-fold after detergent extraction by a single affinity chromatography step on agarose coupled to human chorionic gonadotropin. Receptors were eluted in the free form at pH 3.2 and did not aggregate in the absence of detergent. The purified receptors displayed about 50% of the maximum theoretical binding activity, and retained the high binding affinity and hormonal specificity of the original gonadotropin receptors of the cell membrane.", "contents": "Gonadotropin receptors. Solubilization and purification by affinity chromatography. Specific gonadotropin receptors of the rat testis were purified 15,000-fold after detergent extraction by a single affinity chromatography step on agarose coupled to human chorionic gonadotropin. Receptors were eluted in the free form at pH 3.2 and did not aggregate in the absence of detergent. The purified receptors displayed about 50% of the maximum theoretical binding activity, and retained the high binding affinity and hormonal specificity of the original gonadotropin receptors of the cell membrane."} {"id": "PMID:167009", "title": "Glycogenolytic response to glucagon of cultured fetal hepatocytes. Refractoriness following prior exposure to glucagon.", "content": "The glycogenolytic effect of glucagon has been studied in fetal hepatocytes cultured for 3 to 4 days in the presence of cortisol (10 muM). The hepatocytes, when transplanted from young fetuses (15-day-old), contain only minute amounts of glycogen, whereas when cultured 3 to 4 days in the presence of cortisol, they contain high levels of stored glycogen. Glucagon induced a rapid but partial mobilization of glycogen, which was maximal after 2 hours. The half-maximal response was observed with about 0.1 nM glucagon. The glycogenolytic effect of glucagon in fetal hepatocytes is probably mediated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) as in adult liver. This effect was mimicked by cyclic AMP and N-6, O-2-dibutyryl cyclic AMP, (dibutyryl cyclic AMP), and potentiated by theophylline. Glucagon addition was followed by accumulation of cyclic AMP in the cells within 2 min. Glucagon produces a marked stimulation of the rate of glycogen breakdown and an inhibition of the rate of incorporation of [14-C] glucose into glycogen. The glycogeneolytic effect of a single addition of glucagon was reversed within 4 hours. A second addition of glucagon at this time was unable to induce a new glycogenolytic response. A resistance to glucagon stimulation appeared in the cells after a first exposure to the hormone. This refractoriness was also shown by the loss of glucagon-dependent cyclic AMP accumulation and was not linked to the release by the cells of a \"hormone antagonist\" into the medium. The hepatocytes resistant to the action of glucagon retained their response to cyclic AMP, dibutyryl cyclic AMP, and norepinephrine. Finally, glycogenolytic concentrations of cyclic AMP and of its dibutyryl derivative failed to induce a refractoriness to glucagon.", "contents": "Glycogenolytic response to glucagon of cultured fetal hepatocytes. Refractoriness following prior exposure to glucagon. The glycogenolytic effect of glucagon has been studied in fetal hepatocytes cultured for 3 to 4 days in the presence of cortisol (10 muM). The hepatocytes, when transplanted from young fetuses (15-day-old), contain only minute amounts of glycogen, whereas when cultured 3 to 4 days in the presence of cortisol, they contain high levels of stored glycogen. Glucagon induced a rapid but partial mobilization of glycogen, which was maximal after 2 hours. The half-maximal response was observed with about 0.1 nM glucagon. The glycogenolytic effect of glucagon in fetal hepatocytes is probably mediated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) as in adult liver. This effect was mimicked by cyclic AMP and N-6, O-2-dibutyryl cyclic AMP, (dibutyryl cyclic AMP), and potentiated by theophylline. Glucagon addition was followed by accumulation of cyclic AMP in the cells within 2 min. Glucagon produces a marked stimulation of the rate of glycogen breakdown and an inhibition of the rate of incorporation of [14-C] glucose into glycogen. The glycogeneolytic effect of a single addition of glucagon was reversed within 4 hours. A second addition of glucagon at this time was unable to induce a new glycogenolytic response. A resistance to glucagon stimulation appeared in the cells after a first exposure to the hormone. This refractoriness was also shown by the loss of glucagon-dependent cyclic AMP accumulation and was not linked to the release by the cells of a \"hormone antagonist\" into the medium. The hepatocytes resistant to the action of glucagon retained their response to cyclic AMP, dibutyryl cyclic AMP, and norepinephrine. Finally, glycogenolytic concentrations of cyclic AMP and of its dibutyryl derivative failed to induce a refractoriness to glucagon."} {"id": "PMID:167010", "title": "Kinetics of adenosine triphosphate synthesis in bovine heart submitochondrial particles.", "content": "The kinetics of ATP synthesis by submitochondrial particles were studied with a continuous flow mixing technique allowing measurements of ATP synthesis between 15 and 120 ms after mixing for estimation of the initial rate. During the initial 100 ms, ATP synthesis proceeded at a faster rate when driven by an artificially imposed electrochemical proton gradient than when driven by the respiratory substrate NADH. The rate of ATP synthesis driven by the artificial electrochemical proton gradient was dependent upon the magnitude of the gradient, and was affected similarly by variations of either the pH gradient or membrane potential. Initiation of ATP synthesis driven by NADH oxidation with ADP plus Pi resulted in an initial rate of phosphorylation equivalent to that during steady state respiration. However, a lag in phosphorylation was observed when ATP synthesis was initiated by oxygen or NADH. Valinomycin caused transient uncoupling of ATP synthesis driven by respiration since it strongly inhibited ATP synthesis during the initial 100 ms but it had no effect during steady state phosphorylation. The kinetic results strongly suggest that an electrochemical proton gradient is an obligate intermediate between electron transport and ATP synthesis on the main pathway of energy transduction.", "contents": "Kinetics of adenosine triphosphate synthesis in bovine heart submitochondrial particles. The kinetics of ATP synthesis by submitochondrial particles were studied with a continuous flow mixing technique allowing measurements of ATP synthesis between 15 and 120 ms after mixing for estimation of the initial rate. During the initial 100 ms, ATP synthesis proceeded at a faster rate when driven by an artificially imposed electrochemical proton gradient than when driven by the respiratory substrate NADH. The rate of ATP synthesis driven by the artificial electrochemical proton gradient was dependent upon the magnitude of the gradient, and was affected similarly by variations of either the pH gradient or membrane potential. Initiation of ATP synthesis driven by NADH oxidation with ADP plus Pi resulted in an initial rate of phosphorylation equivalent to that during steady state respiration. However, a lag in phosphorylation was observed when ATP synthesis was initiated by oxygen or NADH. Valinomycin caused transient uncoupling of ATP synthesis driven by respiration since it strongly inhibited ATP synthesis during the initial 100 ms but it had no effect during steady state phosphorylation. The kinetic results strongly suggest that an electrochemical proton gradient is an obligate intermediate between electron transport and ATP synthesis on the main pathway of energy transduction."} {"id": "PMID:167011", "title": "Inactivation of Salmonella phosphoribosylpyrophosphate synthetase by oxidation of a specific sulfhydryl group with potassium permanganate.", "content": "Phosphoribosylpyrophosphate synthetase from Salmonella typhimurium contains four cysteine residues per subunit. Three of these react readily with 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB), forming an active derivative with kinetic and physical properties similar to the native enzyme, but one reacts only under denaturing conditions. Stoichiometric amounts of KMnO4 inactivate the DTNB-treated enzyme. The loss of activity is correlated with the oxidation of the remaining cysteinyl group to cysteic acid by KMnO4. Amino acid analysis indicates that no other residues are altered. The rate of inactivation of the enzyme is decreased 30-fold by saturatin g concentrations of the substrate ATP. Inorganic phosphate also protects substantially against KMnO4. Titration of the native enzyme with limiting amounts of KMnO4 shows that the sulfhydryl group essential for activity competes effectively with the other sulfhydryl groups for KMnO4. These results suggest that the essential sulfhydryl group is near the active site, and that KMnO4, a phosphate analogue, can act as an active site-directed reagent at the ATP binding site of the enzyme. The KMnO4-oxidized enzyme is more highly aggregated than untreated enzyme and fails to bind ATP appreciably.", "contents": "Inactivation of Salmonella phosphoribosylpyrophosphate synthetase by oxidation of a specific sulfhydryl group with potassium permanganate. Phosphoribosylpyrophosphate synthetase from Salmonella typhimurium contains four cysteine residues per subunit. Three of these react readily with 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB), forming an active derivative with kinetic and physical properties similar to the native enzyme, but one reacts only under denaturing conditions. Stoichiometric amounts of KMnO4 inactivate the DTNB-treated enzyme. The loss of activity is correlated with the oxidation of the remaining cysteinyl group to cysteic acid by KMnO4. Amino acid analysis indicates that no other residues are altered. The rate of inactivation of the enzyme is decreased 30-fold by saturatin g concentrations of the substrate ATP. Inorganic phosphate also protects substantially against KMnO4. Titration of the native enzyme with limiting amounts of KMnO4 shows that the sulfhydryl group essential for activity competes effectively with the other sulfhydryl groups for KMnO4. These results suggest that the essential sulfhydryl group is near the active site, and that KMnO4, a phosphate analogue, can act as an active site-directed reagent at the ATP binding site of the enzyme. The KMnO4-oxidized enzyme is more highly aggregated than untreated enzyme and fails to bind ATP appreciably."} {"id": "PMID:167012", "title": "The interaction of human plasma glycoaminoglycans with plasma lipoproteins.", "content": "Modifications of existing methods have allowed for the isolation and purification of various species of plasma glycosaminoglycans on the basis of their sulfate content and molecular size. All of the preparations precipitated human plasma low density lipoproteins (LDL); maximal precipitation occurred with amounts of glycans corresponding to 50 mug of hexuronate and 12 mg of LDL. The interaction of glycans with pyrene-labeled lipoproteins was also studied, measuring variations of the fluorescence emitted by the monomer (M) and excimer (E) species of the bound pyrene. The ratio IE/IM is proportional to c/eta, where c is the microscopic concentration of the pyrene confined to the hydrocarbon region of the lipoprotein and eta is the microviscosity of that region. To 0.12 mg of pyrene-labeled LDL, very low density lipoproteins (VLDL) or high density lipoproteins (HDL) were added increasing amounts of the various glycan preparations. The sulfate-rich species decreased the IE/IM ratio of LDL and HDL but not that of VLDL. This finding suggests that the glycan caused a change in lipoprotein conformation associated with either an increased volume or increased microscopic viscosity of the hydrocarbon region. The modification of LDL conformation could be prevented by proteolytic treatment of the sulfate-rich species or by addition to the system of suitable amounts of sulfate-poor species or of chrondroitin-4-sulfate, but could not be prevented by increased ionic concentration. These results suggest that the two main species of plasma glycans are important in maintaining adequate rheological properties of plasma lipoproteins.", "contents": "The interaction of human plasma glycoaminoglycans with plasma lipoproteins. Modifications of existing methods have allowed for the isolation and purification of various species of plasma glycosaminoglycans on the basis of their sulfate content and molecular size. All of the preparations precipitated human plasma low density lipoproteins (LDL); maximal precipitation occurred with amounts of glycans corresponding to 50 mug of hexuronate and 12 mg of LDL. The interaction of glycans with pyrene-labeled lipoproteins was also studied, measuring variations of the fluorescence emitted by the monomer (M) and excimer (E) species of the bound pyrene. The ratio IE/IM is proportional to c/eta, where c is the microscopic concentration of the pyrene confined to the hydrocarbon region of the lipoprotein and eta is the microviscosity of that region. To 0.12 mg of pyrene-labeled LDL, very low density lipoproteins (VLDL) or high density lipoproteins (HDL) were added increasing amounts of the various glycan preparations. The sulfate-rich species decreased the IE/IM ratio of LDL and HDL but not that of VLDL. This finding suggests that the glycan caused a change in lipoprotein conformation associated with either an increased volume or increased microscopic viscosity of the hydrocarbon region. The modification of LDL conformation could be prevented by proteolytic treatment of the sulfate-rich species or by addition to the system of suitable amounts of sulfate-poor species or of chrondroitin-4-sulfate, but could not be prevented by increased ionic concentration. These results suggest that the two main species of plasma glycans are important in maintaining adequate rheological properties of plasma lipoproteins."} {"id": "PMID:167013", "title": "Stimulation of synthesis of free chondroitin sulfate chains by beta-D-xylosides in cultured cells.", "content": "Beta-Xylosides stimulate 2- to 6-fold the synthesis of glycosaminoglycans by three types of nonconnective tissue cells (RG-C6, NB41A, and rat hepatoma cells, and normal and simian virus 40 (SV40)-transformed normal human skin fibroblasts. The effect, which is specific for the anomeric linkage and the glycone, is observed in the presence and absence of puromycin. Beta-Xylosides may substitute for xylosylated core protein as initiators of synthesis of chondroitin sulfate chains. No stimulation of synthesis of heparan sulfate was observed. With the use of a fluorogenic xyloside, 4-methylumbelliferyl-beta-D-xyloside, it was demonstrated that the free chondroitin sulfate chains secreted into the medium bear the xyloside at the reducing end, and have an average molecular weight of 16,500.", "contents": "Stimulation of synthesis of free chondroitin sulfate chains by beta-D-xylosides in cultured cells. Beta-Xylosides stimulate 2- to 6-fold the synthesis of glycosaminoglycans by three types of nonconnective tissue cells (RG-C6, NB41A, and rat hepatoma cells, and normal and simian virus 40 (SV40)-transformed normal human skin fibroblasts. The effect, which is specific for the anomeric linkage and the glycone, is observed in the presence and absence of puromycin. Beta-Xylosides may substitute for xylosylated core protein as initiators of synthesis of chondroitin sulfate chains. No stimulation of synthesis of heparan sulfate was observed. With the use of a fluorogenic xyloside, 4-methylumbelliferyl-beta-D-xyloside, it was demonstrated that the free chondroitin sulfate chains secreted into the medium bear the xyloside at the reducing end, and have an average molecular weight of 16,500."} {"id": "PMID:167014", "title": "Regulation of glycogen synthetase. Specificity and stoichiometry of phosphorylation of the skeletal muscle enzyme by cyclic 3':5'-AMP-dependent protein kinase.", "content": "Complete conversion of skeletal muscle glycogen synthetase from the I form to the D form requires incorporation of 2 mol of phosphate per enzyme subunit (90,000 g). Incubation of sythetase I with low concentrations of adenosine 3':5'-monophosphate(cAMP)-dependent protein kinase (10 units/ml) and ATP (0.1 to 0.3 mM) plus magnesium acetate (10 mM) results in incorporation within 1/2 hour of 1 mol of phosphate persubunit concomitant with a decrease in the synthetase activity ratio (minus glucose-6-P/plus glucose-6-P) from 0.85 to 0.25. Further incubation for 6 hours does not greatly increase the phosphate content of the synthetase or promote conversion to the D form. This level of phosphorylation is not increased by raising the concentration of protein kinase to 150 units/ml and is not influenced by the presence of glucose-6-P, UDP-glucose, or glycogen. However, at protein kinase concentrations of 10,000 to 30,000 units/ml a second mol of phosphate is incorporated per subunit, and the sythetase activity ratio decreases to 0.05 or less. In addition to the 2 mol of phosphate persubunit which are required for formation of sythetase D, further phosphorylation can be observed which is not associated with changes in synthetase activity. This phosphorylation occurs at a slow rate, is increased by raising the ATP concentration to 2 to 4mM, and is not blocked by the heat-stable protein inhibitor of cAMP-dependent protein kinase. These data indicate that skeletal muscle glycogen synthetase contains multiple phosphorylation sites only two of which are involved in the synthetase I to D conversion.", "contents": "Regulation of glycogen synthetase. Specificity and stoichiometry of phosphorylation of the skeletal muscle enzyme by cyclic 3':5'-AMP-dependent protein kinase. Complete conversion of skeletal muscle glycogen synthetase from the I form to the D form requires incorporation of 2 mol of phosphate per enzyme subunit (90,000 g). Incubation of sythetase I with low concentrations of adenosine 3':5'-monophosphate(cAMP)-dependent protein kinase (10 units/ml) and ATP (0.1 to 0.3 mM) plus magnesium acetate (10 mM) results in incorporation within 1/2 hour of 1 mol of phosphate persubunit concomitant with a decrease in the synthetase activity ratio (minus glucose-6-P/plus glucose-6-P) from 0.85 to 0.25. Further incubation for 6 hours does not greatly increase the phosphate content of the synthetase or promote conversion to the D form. This level of phosphorylation is not increased by raising the concentration of protein kinase to 150 units/ml and is not influenced by the presence of glucose-6-P, UDP-glucose, or glycogen. However, at protein kinase concentrations of 10,000 to 30,000 units/ml a second mol of phosphate is incorporated per subunit, and the sythetase activity ratio decreases to 0.05 or less. In addition to the 2 mol of phosphate persubunit which are required for formation of sythetase D, further phosphorylation can be observed which is not associated with changes in synthetase activity. This phosphorylation occurs at a slow rate, is increased by raising the ATP concentration to 2 to 4mM, and is not blocked by the heat-stable protein inhibitor of cAMP-dependent protein kinase. These data indicate that skeletal muscle glycogen synthetase contains multiple phosphorylation sites only two of which are involved in the synthetase I to D conversion."} {"id": "PMID:167015", "title": "Studies and sequences of Escherichia coli 4.5 S RNA.", "content": "4.5 S RNA, a biologically stable species with electrophoretic properties intermediate between 5 S and transfer RNAs, has been isolated from Escherichia coli and characterized. No function has yet been found for this molecule. Its primary structure and behavior suggests an unusually stable and possibly unique secondary structure. Even from single species of E. coli, there is some sequence heterogeneity within the molecule. The sequence of a major species from MRE 600 is: (see article). Methods for getting sequence overlaps on this highly structured RNA are described, and a possible functional role for 4.5 S RNA is discussed.", "contents": "Studies and sequences of Escherichia coli 4.5 S RNA. 4.5 S RNA, a biologically stable species with electrophoretic properties intermediate between 5 S and transfer RNAs, has been isolated from Escherichia coli and characterized. No function has yet been found for this molecule. Its primary structure and behavior suggests an unusually stable and possibly unique secondary structure. Even from single species of E. coli, there is some sequence heterogeneity within the molecule. The sequence of a major species from MRE 600 is: (see article). Methods for getting sequence overlaps on this highly structured RNA are described, and a possible functional role for 4.5 S RNA is discussed."} {"id": "PMID:167016", "title": "Nucleotide sequence studies of normal and genetically altered glycine transfer ribonucleic acids from Escherichia coli.", "content": "The total nucleotide sequence of tRNAGGA/G -Gly2 from Escherichia coli is pG-C-G-G-G-C-A-U-C-G-U-A-U-A-A-U-G-G-C-U-A-U-U-A-C-C-U-C-A-G-C-C-U-N-C-C-A-A-G-C-U-G-A-U-G-A-U-G-C-G-G-G-T-psi-C-G-A-U-U-C-C-C-G-C-U-G-C-C-C-G-C-U-C-C-AOH, where T- at position 53 is ribothymidylic acid, and psi- at position 54 is pseudouridylic acid; N- at position 36 is an unidentified derivative of uridylic acid, and is present in modified form in a portion of tRNAGGA/G -Gly 2 molecules isolated from E. coli cells. The missense suppressor mutation, glyTsuA36(HA), results in a C yields U base substitution at the 3' end of the anticodon of tRNAGGA/G -Gly 2 (nucleotide position 38). A secondary effect of this base substitution is the modification of the A residue directly adjacent to the 3' end of the anticodon of tRNAsuA36(HA), -Gly 2 suggesting that the enzymes responsible for this modification recognize the anticodon sequences of prospective tRNA substrates. The creation of a missense-suppressing tRNA, tRNAsuA36(HA), -Gly 2 by an alteration of the anticodon sequence of tRNAGGA/G -Gly 2 is analogous to mechanisms whereby other suppressor tRNAs have arisen. The high degree of nucleotide sequence homology between the amino acid acceptor stems and anticodon regions of four glycine isoaccepting tRNAs specified by E. coli and bacteriophage T4 suggests that these regions may be recognized by the glycyl-tRNA synthetase; the involvement of the anticodon region in the synthetase recognition process is supported by the greatly decreased rate of aminoacylation of tRNAsuA36(HA) -Gly 2.", "contents": "Nucleotide sequence studies of normal and genetically altered glycine transfer ribonucleic acids from Escherichia coli. The total nucleotide sequence of tRNAGGA/G -Gly2 from Escherichia coli is pG-C-G-G-G-C-A-U-C-G-U-A-U-A-A-U-G-G-C-U-A-U-U-A-C-C-U-C-A-G-C-C-U-N-C-C-A-A-G-C-U-G-A-U-G-A-U-G-C-G-G-G-T-psi-C-G-A-U-U-C-C-C-G-C-U-G-C-C-C-G-C-U-C-C-AOH, where T- at position 53 is ribothymidylic acid, and psi- at position 54 is pseudouridylic acid; N- at position 36 is an unidentified derivative of uridylic acid, and is present in modified form in a portion of tRNAGGA/G -Gly 2 molecules isolated from E. coli cells. The missense suppressor mutation, glyTsuA36(HA), results in a C yields U base substitution at the 3' end of the anticodon of tRNAGGA/G -Gly 2 (nucleotide position 38). A secondary effect of this base substitution is the modification of the A residue directly adjacent to the 3' end of the anticodon of tRNAsuA36(HA), -Gly 2 suggesting that the enzymes responsible for this modification recognize the anticodon sequences of prospective tRNA substrates. The creation of a missense-suppressing tRNA, tRNAsuA36(HA), -Gly 2 by an alteration of the anticodon sequence of tRNAGGA/G -Gly 2 is analogous to mechanisms whereby other suppressor tRNAs have arisen. The high degree of nucleotide sequence homology between the amino acid acceptor stems and anticodon regions of four glycine isoaccepting tRNAs specified by E. coli and bacteriophage T4 suggests that these regions may be recognized by the glycyl-tRNA synthetase; the involvement of the anticodon region in the synthetase recognition process is supported by the greatly decreased rate of aminoacylation of tRNAsuA36(HA) -Gly 2."} {"id": "PMID:167017", "title": "The nucleotide sequence of a precursor to the glycine- and threonine-specific transfer ribonucleic acids of Escherichia coli.", "content": "The primary nucleotide sequence of an Escherichia coli tRNA precursor molecule has been determined. This precursor RNA, specified by the transducing phage lambdah80dglyTsuA36 thrT tyrT, accumulates in a mutant strain temperature-sensitive for RNase P activity. The 170-nucleotide precursor RNA is processed by E. coli extracts to form mature tRNA Gly 2 suA36 and tRNA Thr ACU/C. The sequence of the precursor is pG-U-U-C-C-A-G-G-A-U-G-C-G-G-G-C-A-U-C-G-U-A-U-A-A-U-G-G-C-U-A-U-U-A-C-C-U-C-A-G-C-C-U-N-C-U-A-A-G-C-U-G-A-U-G-A-U-G-C-G-G-G-T-psi-C-G-A-U-U-C-C-C-G-C-U-G-C-C-C-G-C-U-C-C-A-A-G-A-U-G-U-G-C-U-G-A-U-A-U-A-G-C-U-C-A-G-D-D-G-G-D-A-G-A-G-C-G-C-A-C-C-C-U-U-G-G-U-mt6A-A-G-G-G-U-G-A-G-m7G-U-C-G-G-C-A-G-T-psi-C-G-A-A-U-C-U-G-C-C-U-A-U-C-A-G-C-A-C-C-A-C-U-UOH(tRNA sequences are italicized). It contains the entire primary nucleotide sequences of tRNA Gly2 suA36 and tRNA Thr ACU/C, including the common 3'-terminal sequence, CCA. Nineteen additional nucleotides are present, with 10 at the 5' end, 3 at the 3' end, and the remaining 6 in the inter-tRNA spacer region. RNase P cleaves the precursor specifically at the 5' ends of the mature tRNA sequences.", "contents": "The nucleotide sequence of a precursor to the glycine- and threonine-specific transfer ribonucleic acids of Escherichia coli. The primary nucleotide sequence of an Escherichia coli tRNA precursor molecule has been determined. This precursor RNA, specified by the transducing phage lambdah80dglyTsuA36 thrT tyrT, accumulates in a mutant strain temperature-sensitive for RNase P activity. The 170-nucleotide precursor RNA is processed by E. coli extracts to form mature tRNA Gly 2 suA36 and tRNA Thr ACU/C. The sequence of the precursor is pG-U-U-C-C-A-G-G-A-U-G-C-G-G-G-C-A-U-C-G-U-A-U-A-A-U-G-G-C-U-A-U-U-A-C-C-U-C-A-G-C-C-U-N-C-U-A-A-G-C-U-G-A-U-G-A-U-G-C-G-G-G-T-psi-C-G-A-U-U-C-C-C-G-C-U-G-C-C-C-G-C-U-C-C-A-A-G-A-U-G-U-G-C-U-G-A-U-A-U-A-G-C-U-C-A-G-D-D-G-G-D-A-G-A-G-C-G-C-A-C-C-C-U-U-G-G-U-mt6A-A-G-G-G-U-G-A-G-m7G-U-C-G-G-C-A-G-T-psi-C-G-A-A-U-C-U-G-C-C-U-A-U-C-A-G-C-A-C-C-A-C-U-UOH(tRNA sequences are italicized). It contains the entire primary nucleotide sequences of tRNA Gly2 suA36 and tRNA Thr ACU/C, including the common 3'-terminal sequence, CCA. Nineteen additional nucleotides are present, with 10 at the 5' end, 3 at the 3' end, and the remaining 6 in the inter-tRNA spacer region. RNase P cleaves the precursor specifically at the 5' ends of the mature tRNA sequences."} {"id": "PMID:167018", "title": "The nucleotide sequence in the promoter region of the gene N in bacteriophage lambda.", "content": "The sequence of 18 nucleotides in the region preceding the initiation of transcription of the gene N of bacteriophage lambda has been determined to be as follows (see article). The basic approach used for the sequence determination involved Escherichia coli DNA polymerase I-catalyzed elongation of the octadecanucleotide primer, dT-C-A-G-T-G-C-G-T-C-C-T-G-C-T-G-A-rU, possessing the appropriate polarity and nucleotide sequence corresponding to the 5' end of the gene N transcript. Following hybridization of the primer to the r-stand of bacteriophage lambda CI85657, sequences of the newly grown ollgonucleotide chains were determined by a) partial exonuclease digestion followed by two-dimensional fingerprinting; b) determination of pyrimidine tracts; and c) nearest neighbor analyses. Primer elongation was carried out in a controlled manner, the size of the newly grown chains being kept short by the following techniques: a) insertion of a ribonucleotide unit as the 3' terminus of the primer; b) use of a limited number of deoxynucleoside 5'-triphosphates in the elongation reaction; and c) enlongation of the primer using all the four nucleoside triphosphates with one of the triphosphates being supplied in a limiting concentration.", "contents": "The nucleotide sequence in the promoter region of the gene N in bacteriophage lambda. The sequence of 18 nucleotides in the region preceding the initiation of transcription of the gene N of bacteriophage lambda has been determined to be as follows (see article). The basic approach used for the sequence determination involved Escherichia coli DNA polymerase I-catalyzed elongation of the octadecanucleotide primer, dT-C-A-G-T-G-C-G-T-C-C-T-G-C-T-G-A-rU, possessing the appropriate polarity and nucleotide sequence corresponding to the 5' end of the gene N transcript. Following hybridization of the primer to the r-stand of bacteriophage lambda CI85657, sequences of the newly grown ollgonucleotide chains were determined by a) partial exonuclease digestion followed by two-dimensional fingerprinting; b) determination of pyrimidine tracts; and c) nearest neighbor analyses. Primer elongation was carried out in a controlled manner, the size of the newly grown chains being kept short by the following techniques: a) insertion of a ribonucleotide unit as the 3' terminus of the primer; b) use of a limited number of deoxynucleoside 5'-triphosphates in the elongation reaction; and c) enlongation of the primer using all the four nucleoside triphosphates with one of the triphosphates being supplied in a limiting concentration."} {"id": "PMID:167019", "title": "The regulation of phosphoenolpyruvate carboxykinase (GTP) synthesis in rat kidney cortex. The role of acid-base balance and glucocorticoids.", "content": "The effects of metabolic acidosis and of hormones on the activity, synthesis, and degradation of renal cytosolic P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) were studied in the rat using isotopic -immunochemical procedures. At normal acid-base balance, the synthesis of the enzyme accounted for between 2 and 3.5% of the synthesis of all soluble protein in the kidney cortex. P-enolpyruvate carboxykinase synthesis was selectively stimulated in acute metabolic acidosis, so that the relative rate of synthesis of the enzyme was increased to 7% 13 hours after oral administration of ammonium chloride. The stimulation of P-enolpyruvate carboxykinase synthesis preceded any increase in the assayable activity of the enzyme. The administration of sodium bicarbonate to acutely acidotic rats returned the rate of enzyme synthesis to normal in 8 hours. The effect of acidosis on both the synthesis and the activity of P-enolpyruvate carboxykinase was prevented by actinomycin D, cordycepin, and cycloheximide. The degradation in vivo of pulse-labeled P-enolpyruvate carboxykinase was not affected by acidosis. Thus, the stimulation of P-enolpyruvate carboxykinase synthesis is the major mechanism for the increase in the level of the enzyme observed in metabolic acidosis. The administration of glucocorticoid triamcinolone resulted in an increase in the relative rate of P-enolpyruvate carboxykinase synthesis and a commensurate increase in the activity of the enzyme in the renal cortex. Both changes were abolished by actinomycin D. Fasting was characterized by a high enzyme activity and a rapid rate of enzyme synthesis in the kidney cortex. This high rate of synthesis was reduced after the administration of sodium bicarbonate, but not after glucose feeding. Moreover, the injection of insulin to diabetic rats did not repress P-enolpyruvate carboxykinase synthesis in the renal cortex. Theophylline plus N-6, 0-2'-dibutyryl adenosine 3':5'-monophosphate stimulated P-enolpyruvate carboxykinase synthesis in the kidney of intact rats. However, the latter effect was probably due to glucocorticoid secretion, since it did not occur in adrenalectomized animals. The administration of parathyroid extracts did not result in the induction of the enzyme. Thus, the hormonal regulation of cytosolic P-enolpyruvate carboxykinase synthesis in the kidney differs markedly from that in the liver.", "contents": "The regulation of phosphoenolpyruvate carboxykinase (GTP) synthesis in rat kidney cortex. The role of acid-base balance and glucocorticoids. The effects of metabolic acidosis and of hormones on the activity, synthesis, and degradation of renal cytosolic P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) were studied in the rat using isotopic -immunochemical procedures. At normal acid-base balance, the synthesis of the enzyme accounted for between 2 and 3.5% of the synthesis of all soluble protein in the kidney cortex. P-enolpyruvate carboxykinase synthesis was selectively stimulated in acute metabolic acidosis, so that the relative rate of synthesis of the enzyme was increased to 7% 13 hours after oral administration of ammonium chloride. The stimulation of P-enolpyruvate carboxykinase synthesis preceded any increase in the assayable activity of the enzyme. The administration of sodium bicarbonate to acutely acidotic rats returned the rate of enzyme synthesis to normal in 8 hours. The effect of acidosis on both the synthesis and the activity of P-enolpyruvate carboxykinase was prevented by actinomycin D, cordycepin, and cycloheximide. The degradation in vivo of pulse-labeled P-enolpyruvate carboxykinase was not affected by acidosis. Thus, the stimulation of P-enolpyruvate carboxykinase synthesis is the major mechanism for the increase in the level of the enzyme observed in metabolic acidosis. The administration of glucocorticoid triamcinolone resulted in an increase in the relative rate of P-enolpyruvate carboxykinase synthesis and a commensurate increase in the activity of the enzyme in the renal cortex. Both changes were abolished by actinomycin D. Fasting was characterized by a high enzyme activity and a rapid rate of enzyme synthesis in the kidney cortex. This high rate of synthesis was reduced after the administration of sodium bicarbonate, but not after glucose feeding. Moreover, the injection of insulin to diabetic rats did not repress P-enolpyruvate carboxykinase synthesis in the renal cortex. Theophylline plus N-6, 0-2'-dibutyryl adenosine 3':5'-monophosphate stimulated P-enolpyruvate carboxykinase synthesis in the kidney of intact rats. However, the latter effect was probably due to glucocorticoid secretion, since it did not occur in adrenalectomized animals. The administration of parathyroid extracts did not result in the induction of the enzyme. Thus, the hormonal regulation of cytosolic P-enolpyruvate carboxykinase synthesis in the kidney differs markedly from that in the liver."} {"id": "PMID:167020", "title": "A spin label study of egg white avidin.", "content": "Avidin is a tetrametric protein (mass 68,000 daltons) that binds 4 molecules of vitamin biotin (1). The biotin binding sites, 1 per subunit, are grouped in two pairs at opposite ends of the avidin molecule (GREEN, N.M., KONIECZNY, L., TOMS, E.J., and VALENTINE, R.C. (1971) Biochem. J. 125, 781). We have studied the topography of the avidin binding sites with the aid of four spin-labeled analogs of biotin: 4-biotinamido-2,2,6,6-tetramethyl-1-piperidinyloxy (II), 3-biotinamido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (III), 3-biotinamidomethyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (IV), 4-(biotinylglycyl)-amino-2,2,6,6-tetramethyl-1-piperidinyloxy (V). Fluorescence and optical absorption spectroscopy indicated that II to V occupied the same binding sites on avidin as did biotin. The electron spin resonance spectrum of the 4:1 complex between II and avidin contained broad line components characteristic of a highly immobilized spin label. Dipole-dipole interactions between spin labels bound to adjacent sites split each of the three major hyperfine lines into doublets with a separation of 13.8 G. The distance between adjacent bound nitroxide groups was calculated from this splitting to be 16 A. The dissociation of the 4:1 complex between II and avidin was biphasic with approximately half of the labels dissociating at a rate (kdiss equal to 2.51 times 10- minus 4 s- minus 1) that was much faster than the remainder (kdiss equal to 1.22 times 10- minus 5 s- minus 1). The electron spin resonance spectrum of the 2:1 complex between II and avidin clearly showed that, immediately after mixing, the spin labels were distributed in a random fashion among the available binding sites but that they slowly redistributed themselves so that each label bound to a site which was adjacent to an unoccupied site. The final time-independent electron spin resonance spectrum exhibited a splitting 69 G between the low and high field hyperfine lines which is characteristic of a highly immobilized, noninteracting spin label. Spin labels III and IV interacted with avidin in a similar fashion to that described for II with the exception that their dipolar splittings were 11.9 G and 14.2 G, respectively. From these splittings it was estimated that the distance between adjacent avidin-bound nitroxides was 16.7 A for labeled III and 15.7 A for label IV. The electron spin resonance spectrum of label V bound to avidin was characteristic of a noninteracting highly immobilized nitroxide with a maximum splitting of 62 G. The spectrum of V bound to avidin was independent of both time and the amount of bound label. The rate of dissociation of V from a 4:1 complex with avidin was monophasic. A model is proposed in which the recognition site for the heterocyclic ring system of biotin is represented as a cleft located within a hydrophobic depression in the surface of avidin.", "contents": "A spin label study of egg white avidin. Avidin is a tetrametric protein (mass 68,000 daltons) that binds 4 molecules of vitamin biotin (1). The biotin binding sites, 1 per subunit, are grouped in two pairs at opposite ends of the avidin molecule (GREEN, N.M., KONIECZNY, L., TOMS, E.J., and VALENTINE, R.C. (1971) Biochem. J. 125, 781). We have studied the topography of the avidin binding sites with the aid of four spin-labeled analogs of biotin: 4-biotinamido-2,2,6,6-tetramethyl-1-piperidinyloxy (II), 3-biotinamido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (III), 3-biotinamidomethyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (IV), 4-(biotinylglycyl)-amino-2,2,6,6-tetramethyl-1-piperidinyloxy (V). Fluorescence and optical absorption spectroscopy indicated that II to V occupied the same binding sites on avidin as did biotin. The electron spin resonance spectrum of the 4:1 complex between II and avidin contained broad line components characteristic of a highly immobilized spin label. Dipole-dipole interactions between spin labels bound to adjacent sites split each of the three major hyperfine lines into doublets with a separation of 13.8 G. The distance between adjacent bound nitroxide groups was calculated from this splitting to be 16 A. The dissociation of the 4:1 complex between II and avidin was biphasic with approximately half of the labels dissociating at a rate (kdiss equal to 2.51 times 10- minus 4 s- minus 1) that was much faster than the remainder (kdiss equal to 1.22 times 10- minus 5 s- minus 1). The electron spin resonance spectrum of the 2:1 complex between II and avidin clearly showed that, immediately after mixing, the spin labels were distributed in a random fashion among the available binding sites but that they slowly redistributed themselves so that each label bound to a site which was adjacent to an unoccupied site. The final time-independent electron spin resonance spectrum exhibited a splitting 69 G between the low and high field hyperfine lines which is characteristic of a highly immobilized, noninteracting spin label. Spin labels III and IV interacted with avidin in a similar fashion to that described for II with the exception that their dipolar splittings were 11.9 G and 14.2 G, respectively. From these splittings it was estimated that the distance between adjacent avidin-bound nitroxides was 16.7 A for labeled III and 15.7 A for label IV. The electron spin resonance spectrum of label V bound to avidin was characteristic of a noninteracting highly immobilized nitroxide with a maximum splitting of 62 G. The spectrum of V bound to avidin was independent of both time and the amount of bound label. The rate of dissociation of V from a 4:1 complex with avidin was monophasic. A model is proposed in which the recognition site for the heterocyclic ring system of biotin is represented as a cleft located within a hydrophobic depression in the surface of avidin."} {"id": "PMID:167021", "title": "Enhanced differential synthesis of proteins in a mammalian cell-free system by addition of polyamines.", "content": "Addition of the polyamines spermidine, spermine, or putrescine to a fractionated mammalian cell-free protein-synthesis system programmed by a variety of mRNAs results in a 3- to 5-fold stimulation of amino acid incorporation over that found in the absence of added polyamine. The mRNAs used as template were adenovirus mRNA, globin 9s mRNA, and RNA from the bacteriophages R17, Qbeta, and MS2. The relative amounts of 10 adenovirus polypeptides synthesized in vitro are altered by the addition of polyamines to the translation system to reflect more closely the relative amounts of these polypeptides synthesized in vivo. This qualititive improvement in translation products on addition of polyamines allow the analysis of a number of products which are at best only marginally synthesized in the absence of added polyamines. The low level of synthesis due to endogenous mRNA is stimulated by spermidine and spermine but a lesser extent by putrescine.", "contents": "Enhanced differential synthesis of proteins in a mammalian cell-free system by addition of polyamines. Addition of the polyamines spermidine, spermine, or putrescine to a fractionated mammalian cell-free protein-synthesis system programmed by a variety of mRNAs results in a 3- to 5-fold stimulation of amino acid incorporation over that found in the absence of added polyamine. The mRNAs used as template were adenovirus mRNA, globin 9s mRNA, and RNA from the bacteriophages R17, Qbeta, and MS2. The relative amounts of 10 adenovirus polypeptides synthesized in vitro are altered by the addition of polyamines to the translation system to reflect more closely the relative amounts of these polypeptides synthesized in vivo. This qualititive improvement in translation products on addition of polyamines allow the analysis of a number of products which are at best only marginally synthesized in the absence of added polyamines. The low level of synthesis due to endogenous mRNA is stimulated by spermidine and spermine but a lesser extent by putrescine."} {"id": "PMID:167022", "title": "The interaction of NADH-cytochrome b5 reductase and cytochrome b5 bound to egg lecithin liposomes.", "content": "Incubation of liposomes prepared by sonication of egg lecithin with the amphipathic form of cytochrome b5 results in the binding of a maximum of 244 molecules of cytochrome b5 per liposomal vesicle. Interactions of the phospholipid with the hydrophobic segment of cytochrome b5 are involved in this binding which does not disrupt the liposome. When a small amount of NADH-cytochrome b5 reductase is bound liposomes simultaneously with cytochrome b5, the two proteins catalyze the reduction of cytochrome c by NADH. A qualitative kinetic analysis reveals that all of the cytochrome b5 interacts with reductase, a result consistent with these protein undergoing translational diffusion in the plane of the membrane. This system and the purified stearyl coenzyme A desaturase provide a model to study the dynamics of protein andlipid interactions in this membrane-bound oxidative sequence.", "contents": "The interaction of NADH-cytochrome b5 reductase and cytochrome b5 bound to egg lecithin liposomes. Incubation of liposomes prepared by sonication of egg lecithin with the amphipathic form of cytochrome b5 results in the binding of a maximum of 244 molecules of cytochrome b5 per liposomal vesicle. Interactions of the phospholipid with the hydrophobic segment of cytochrome b5 are involved in this binding which does not disrupt the liposome. When a small amount of NADH-cytochrome b5 reductase is bound liposomes simultaneously with cytochrome b5, the two proteins catalyze the reduction of cytochrome c by NADH. A qualitative kinetic analysis reveals that all of the cytochrome b5 interacts with reductase, a result consistent with these protein undergoing translational diffusion in the plane of the membrane. This system and the purified stearyl coenzyme A desaturase provide a model to study the dynamics of protein andlipid interactions in this membrane-bound oxidative sequence."} {"id": "PMID:167023", "title": "Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro.", "content": "In vitro incubation of frog erythrocytes with (minus)-isoproterenol, 0.1 mM, at 23 degrees for 10 to 24 hours caused a 63% decline (rho less than 0.001) in the maximum (minus)-isoproterenol-stimulated adenylate cyclase activity in the erythrocyte membranes. Affinity for (minus)-isoproterenol as judged by the concentration which half-maximally stimulated the enzyme was not markedly altered. Basal enzyme activity and stimulation by fluoride or prostaglandin E1 remained unaltered. The number of beta-adrenergic receptor binding sites, assessed by binding studies with the beta-adrenergic antagonist (minus)-[3-H] alprenolol, declined by 50% (rho less than 0.005) in the (minus)-isoproterenol-treated cells. The binding affinity of the sites was not changed. Regulation of the concentration of functionally active beta-adrenergic receptors in membranes may be one of the mechanisms by which chronic exposure to catecholamines desensitizes tissues to beta-adrenergic stimulation.", "contents": "Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. In vitro incubation of frog erythrocytes with (minus)-isoproterenol, 0.1 mM, at 23 degrees for 10 to 24 hours caused a 63% decline (rho less than 0.001) in the maximum (minus)-isoproterenol-stimulated adenylate cyclase activity in the erythrocyte membranes. Affinity for (minus)-isoproterenol as judged by the concentration which half-maximally stimulated the enzyme was not markedly altered. Basal enzyme activity and stimulation by fluoride or prostaglandin E1 remained unaltered. The number of beta-adrenergic receptor binding sites, assessed by binding studies with the beta-adrenergic antagonist (minus)-[3-H] alprenolol, declined by 50% (rho less than 0.005) in the (minus)-isoproterenol-treated cells. The binding affinity of the sites was not changed. Regulation of the concentration of functionally active beta-adrenergic receptors in membranes may be one of the mechanisms by which chronic exposure to catecholamines desensitizes tissues to beta-adrenergic stimulation."} {"id": "PMID:167024", "title": "Isolation of a unique peptide inhibitor of hormone-responsive adenylate cyclase.", "content": "We have perfused isolated rat livers with hypocalcemic (4.4 mg 100 ml) Krebs-Ringer bicarbonate albumin buffer. After 15 min of perfusion, a substance appeared in the perfusate which decreased rat renal adenylate cyclase activation by parathyroid hormone (PTH). The material in the perfusate was purified greater than 50,000-fold by Bio-Gel P-10 chromatography. The purified antagonist decreased the activation of rat renal cortical adenylate cyclase by PTH, glucagon, and epinephrine 75 to 100%. Concentration response curves for each of the hormones indicated a noncompetitive interaction of the inhibitor with the hormone. The inhibition was not species-specific, as the activation of the parathyroid hormone-responsive adenylate cyclase in cat renal cortex was also abolished by the inhibitor from the perfused rat liver. The inhibitor is a peptide, Mr equal to similar to 1000, which is heat-stable, acid-stable, alkai-labile, and is destroyed by trypsin, leucine aminopeptidase, and elastase. It is not destroyed by phosphodiesterase, 5'-nucleotidase, alkaline phosphatase, neuraminidase, RNase, or phospholipase A. The inhibitor is not produced by isolated rat livers perfused with normocalcemic perfusion media. It is unclear whether the peptide is synthesized by the liver or whether it is a breakdown product of a larger peptide or protein in the liver. This is the first reported peptide inhibitor of adenylate cyclase.", "contents": "Isolation of a unique peptide inhibitor of hormone-responsive adenylate cyclase. We have perfused isolated rat livers with hypocalcemic (4.4 mg 100 ml) Krebs-Ringer bicarbonate albumin buffer. After 15 min of perfusion, a substance appeared in the perfusate which decreased rat renal adenylate cyclase activation by parathyroid hormone (PTH). The material in the perfusate was purified greater than 50,000-fold by Bio-Gel P-10 chromatography. The purified antagonist decreased the activation of rat renal cortical adenylate cyclase by PTH, glucagon, and epinephrine 75 to 100%. Concentration response curves for each of the hormones indicated a noncompetitive interaction of the inhibitor with the hormone. The inhibition was not species-specific, as the activation of the parathyroid hormone-responsive adenylate cyclase in cat renal cortex was also abolished by the inhibitor from the perfused rat liver. The inhibitor is a peptide, Mr equal to similar to 1000, which is heat-stable, acid-stable, alkai-labile, and is destroyed by trypsin, leucine aminopeptidase, and elastase. It is not destroyed by phosphodiesterase, 5'-nucleotidase, alkaline phosphatase, neuraminidase, RNase, or phospholipase A. The inhibitor is not produced by isolated rat livers perfused with normocalcemic perfusion media. It is unclear whether the peptide is synthesized by the liver or whether it is a breakdown product of a larger peptide or protein in the liver. This is the first reported peptide inhibitor of adenylate cyclase."} {"id": "PMID:167026", "title": "The effectiveness of various antibiotics in methyl methacrylate.", "content": "The effectiveness of different antibiotics mixed with Simplex P has been tested in vitro. A laboratory model was designed to simulate the constant immersion of bone cement in tissue fluid. Clindamycin, and to a lesser extent Cephalothin, were shown to be effective when used in this manner against Staphylococcus aureus and epidermidis. Effective inhibition of Gram-negative organisms could not be demonstrated with any of the antibiotics tested. The addition of up to 3 grams of antibiotic powder per unit of 40 grams of Simplex P did not appear to alter the expansive properties of the cement. Such release of antibiotics as did occur was thought to be related to the slow absorption of water by the slightly porous methyl methacrylate.", "contents": "The effectiveness of various antibiotics in methyl methacrylate. The effectiveness of different antibiotics mixed with Simplex P has been tested in vitro. A laboratory model was designed to simulate the constant immersion of bone cement in tissue fluid. Clindamycin, and to a lesser extent Cephalothin, were shown to be effective when used in this manner against Staphylococcus aureus and epidermidis. Effective inhibition of Gram-negative organisms could not be demonstrated with any of the antibiotics tested. The addition of up to 3 grams of antibiotic powder per unit of 40 grams of Simplex P did not appear to alter the expansive properties of the cement. Such release of antibiotics as did occur was thought to be related to the slow absorption of water by the slightly porous methyl methacrylate."} {"id": "PMID:167028", "title": "Isolation and subfractionation on ficoll gradients of adult rat hepatocytes. Size, morphology, and biochemical characteristics of cell fractions.", "content": "The recirculating perfusion of adult rat liver with a Ca-++-free Hanks' solution produces a release of the adhesiveness of cells and a cleaving of the desmosomes. The addition of collagenase and hyaluronidase to the perfusion medium leads to complete dissociation of the liver tissue into a mixture of isolated cells and cell cords in which the hepatocytes remain connected with specific junctional differentiations, namely the gap and tight junctions. Individual cells are released by submitting the suspension of cell trabeculae to a gentle rolling. The gap junctions are ruptured at least in one of the two adjacent cells and remain generally attached to the other cell taking with them a small portion of cytoplasm. This technique of isolation of hepatocytes yields about 60-65% of the parenchymal cells contained in a liver; endothelial cells and other cells of the connective tissue are not recovered. The ultrastructural preservation of the isolated hepatocytes is excellent and the glucose-6-phosphatase activity, confined to the endoplasmic reticulum, appears unaltered in most cells. Protein, DNA and RNA recovery in the preparations of isolated hepatocytes is satisfactory, amounting to 70% of that found in liver homogenate; glycogen, the most labile component examined, is partly lost or degraded during the manipulations. Cell diameters measured by different methods confirm the preservation of the original volume of the in situ hepatocytes and the presence of more than one type of parenchymal cell. By submitting this heterogeneous cell population to an isopycnic density gradient centrifugation, two types of hepatocytes can be distinguished: the light hepatocytes, with a mean diameter of 20.5 mum and a mean density of 1.10, are characterized by an extended smooth-walled endoplasmic reticulum entrapping dispersed alpha-glycogen particles; the heavy hepatocytes, with a mean diameter of 19.0 mum and a mean density of 1.14, present a relatively reduced compartment of smooth endoplasmic reticulum, but large accumulations of glycogen. It is suggested that the cell fraction of low density is enriched in centrolobular cells and the high density fraction in perilobular hepatocytes.", "contents": "Isolation and subfractionation on ficoll gradients of adult rat hepatocytes. Size, morphology, and biochemical characteristics of cell fractions. The recirculating perfusion of adult rat liver with a Ca-++-free Hanks' solution produces a release of the adhesiveness of cells and a cleaving of the desmosomes. The addition of collagenase and hyaluronidase to the perfusion medium leads to complete dissociation of the liver tissue into a mixture of isolated cells and cell cords in which the hepatocytes remain connected with specific junctional differentiations, namely the gap and tight junctions. Individual cells are released by submitting the suspension of cell trabeculae to a gentle rolling. The gap junctions are ruptured at least in one of the two adjacent cells and remain generally attached to the other cell taking with them a small portion of cytoplasm. This technique of isolation of hepatocytes yields about 60-65% of the parenchymal cells contained in a liver; endothelial cells and other cells of the connective tissue are not recovered. The ultrastructural preservation of the isolated hepatocytes is excellent and the glucose-6-phosphatase activity, confined to the endoplasmic reticulum, appears unaltered in most cells. Protein, DNA and RNA recovery in the preparations of isolated hepatocytes is satisfactory, amounting to 70% of that found in liver homogenate; glycogen, the most labile component examined, is partly lost or degraded during the manipulations. Cell diameters measured by different methods confirm the preservation of the original volume of the in situ hepatocytes and the presence of more than one type of parenchymal cell. By submitting this heterogeneous cell population to an isopycnic density gradient centrifugation, two types of hepatocytes can be distinguished: the light hepatocytes, with a mean diameter of 20.5 mum and a mean density of 1.10, are characterized by an extended smooth-walled endoplasmic reticulum entrapping dispersed alpha-glycogen particles; the heavy hepatocytes, with a mean diameter of 19.0 mum and a mean density of 1.14, present a relatively reduced compartment of smooth endoplasmic reticulum, but large accumulations of glycogen. It is suggested that the cell fraction of low density is enriched in centrolobular cells and the high density fraction in perilobular hepatocytes."} {"id": "PMID:167029", "title": "Isolation of centrolobular and perilobular hepatocytes after phenobarbital treatment.", "content": "Daily phenobarbital (PB) injections, on 3-7 consecutive days, induce an intense proliferation of smooth endoplasmic reticulum (ER) associated with a decrease of the glucose-6-phosphatase activity. This situation first affects the centrolobular hepatocytes, enhancing the degree of liver lobule heterogeneity. This experimental model was used for isolation and further subfractionation of hepatocytes on Ficoll density gradients, as described in the preceding paper. Profiles of protein, DNA, RNA, glycogen, phosphorylase, and glucose-6-phosphatase were determined all along the gradient. Two liver cell populations were distinguished: (a) light hepatocytes (mean density 1.10) present the same morphological characteristics as centrolobular cells, i.e., an abundant smooth ER composed of tubular elements, numerous small mitochondria, and few glycogen particles; (b) heavy hepatocytes (mean density 1.14) are characterized by large and compact glycogen areas and prominent rough endoplasmic cisternae, as are the perilobular cells. After incubation in the Wachstein-Meisel medium, Centrolobular hepatocytes exhibit dispersed reaction sites of glucose-6-phosphatase activity, whereas perilobular cells present a continuous and intense reaction. Morphometric determinations were carried out for both cell populations. Centrolobular PB hepatocytes are considerably enlarged (mean diameter: 23.7 mum); perilobular hepatocytes have a significantly smaller mean diameter of 19.2 mum, which is close to the values of control liver cells.", "contents": "Isolation of centrolobular and perilobular hepatocytes after phenobarbital treatment. Daily phenobarbital (PB) injections, on 3-7 consecutive days, induce an intense proliferation of smooth endoplasmic reticulum (ER) associated with a decrease of the glucose-6-phosphatase activity. This situation first affects the centrolobular hepatocytes, enhancing the degree of liver lobule heterogeneity. This experimental model was used for isolation and further subfractionation of hepatocytes on Ficoll density gradients, as described in the preceding paper. Profiles of protein, DNA, RNA, glycogen, phosphorylase, and glucose-6-phosphatase were determined all along the gradient. Two liver cell populations were distinguished: (a) light hepatocytes (mean density 1.10) present the same morphological characteristics as centrolobular cells, i.e., an abundant smooth ER composed of tubular elements, numerous small mitochondria, and few glycogen particles; (b) heavy hepatocytes (mean density 1.14) are characterized by large and compact glycogen areas and prominent rough endoplasmic cisternae, as are the perilobular cells. After incubation in the Wachstein-Meisel medium, Centrolobular hepatocytes exhibit dispersed reaction sites of glucose-6-phosphatase activity, whereas perilobular cells present a continuous and intense reaction. Morphometric determinations were carried out for both cell populations. Centrolobular PB hepatocytes are considerably enlarged (mean diameter: 23.7 mum); perilobular hepatocytes have a significantly smaller mean diameter of 19.2 mum, which is close to the values of control liver cells."} {"id": "PMID:167030", "title": "Receptor mobility and the binding of cells to lectin-coated fibers.", "content": "The ability of cells to bind to nylon fibers coated with lectin molecules interspaced with varying numbers of albumin molecules has been analyzed. The cells used were lymphoma cells, normal lymphocytes, myeloid leukemia cells, and normal and transformed fibroblasts, and the fibers were coated with different densities of concanavalin A or the lectins from soybean or wheat germ. Cells fixed with glutaraldehyde did not bind to lectin-coated fibers. The number of cells bound to fibers could be increased by increasing the density of lectin molecules on the fiber, the density of specific receptors on the cell, or the mobility of the receptors. It is suggested that binding of cells to fibers involves alignment and binding of specific cell surface receptors with lectin molecules immobilized on the fibers, and that this alignment requires short-range rapid lateral mobility (RLM) of the receptors. The titration of cell binding to fibers coated with different densities of lectin and albumin has been used to measure the relative RLM of unoccupied cell surface receptors for the lectin. The results indicate a relationship of RLM to lectin-induced cell-to-cell binding. The RLM or receptors for concanavalin A (Con A) was generally found to be higher than that of receptors for the lectins from wheat germ or soybean. Receptor RLM could be decreased by use of metabolic inhibitors or by lowering the temperature. Receptors for Con A had a lower RLM on normal fibroblasts than on SV40-transformed fibroblasts, and trypsinization of normal fibroblasts increased Con A receptor RLM. Normal lymphocytes, lymphoma cells, and lines of myeloid leukemia cells that can be induced to differentiate had a high receptor RLM, whereas lines of myeloid leukemia cells that could not be induced to differentiate had a low receptor RLM. These results suggest that the RLM of Con A receptors is related to the transformation of fibroblasts and the ability of myeloid leukemia cells to undergo differentiation", "contents": "Receptor mobility and the binding of cells to lectin-coated fibers. The ability of cells to bind to nylon fibers coated with lectin molecules interspaced with varying numbers of albumin molecules has been analyzed. The cells used were lymphoma cells, normal lymphocytes, myeloid leukemia cells, and normal and transformed fibroblasts, and the fibers were coated with different densities of concanavalin A or the lectins from soybean or wheat germ. Cells fixed with glutaraldehyde did not bind to lectin-coated fibers. The number of cells bound to fibers could be increased by increasing the density of lectin molecules on the fiber, the density of specific receptors on the cell, or the mobility of the receptors. It is suggested that binding of cells to fibers involves alignment and binding of specific cell surface receptors with lectin molecules immobilized on the fibers, and that this alignment requires short-range rapid lateral mobility (RLM) of the receptors. The titration of cell binding to fibers coated with different densities of lectin and albumin has been used to measure the relative RLM of unoccupied cell surface receptors for the lectin. The results indicate a relationship of RLM to lectin-induced cell-to-cell binding. The RLM or receptors for concanavalin A (Con A) was generally found to be higher than that of receptors for the lectins from wheat germ or soybean. Receptor RLM could be decreased by use of metabolic inhibitors or by lowering the temperature. Receptors for Con A had a lower RLM on normal fibroblasts than on SV40-transformed fibroblasts, and trypsinization of normal fibroblasts increased Con A receptor RLM. Normal lymphocytes, lymphoma cells, and lines of myeloid leukemia cells that can be induced to differentiate had a high receptor RLM, whereas lines of myeloid leukemia cells that could not be induced to differentiate had a low receptor RLM. These results suggest that the RLM of Con A receptors is related to the transformation of fibroblasts and the ability of myeloid leukemia cells to undergo differentiation"} {"id": "PMID:167031", "title": "The relation between sporulation and the induction of antibiotic synthesis and of amino acid uptake in Bacillus brevis.", "content": "The induction and localization of tyrocidine-synthesizing enzymes is shown to be parallel, during growth of Bacillus brevis (ATCC 8185, American Type Culture Collection, Rockville, Md.), with the induction of uptake of constitutive amino acids and of components of pantetheine, a coenzyme of tyrocidine synthesis. Antibiotic synthesis appears at the end of logarithmic growth when the first soluble enzymes may be obtained from homogenates. During this period, binding proteins for metabolite uptake were isolated by intensive sonication which, when studied by chromatography, were identified by the appearance of low molecular weight fractions binding the radioactively marked metabolites; their induction was prevented by addition of rifampicin. The major purpose of this study was a comparison of antibiotic production and sporulation, the progress of which was followed by electron microscopy. The onset of tyrocidine synthesis and metabolite uptake coincided with the appearance of septum formation indicating that sporulation had progressed to stage II. With the progress of spore encapsulation, the tyrocidine production migrated from the soluble fraction into the forespore, terminating with the separation of forespores from the sporangium membrane. The resulting concentration of antibiotic in the forespore may indicate its function in sporulation, the nature of which, however, was not explored.", "contents": "The relation between sporulation and the induction of antibiotic synthesis and of amino acid uptake in Bacillus brevis. The induction and localization of tyrocidine-synthesizing enzymes is shown to be parallel, during growth of Bacillus brevis (ATCC 8185, American Type Culture Collection, Rockville, Md.), with the induction of uptake of constitutive amino acids and of components of pantetheine, a coenzyme of tyrocidine synthesis. Antibiotic synthesis appears at the end of logarithmic growth when the first soluble enzymes may be obtained from homogenates. During this period, binding proteins for metabolite uptake were isolated by intensive sonication which, when studied by chromatography, were identified by the appearance of low molecular weight fractions binding the radioactively marked metabolites; their induction was prevented by addition of rifampicin. The major purpose of this study was a comparison of antibiotic production and sporulation, the progress of which was followed by electron microscopy. The onset of tyrocidine synthesis and metabolite uptake coincided with the appearance of septum formation indicating that sporulation had progressed to stage II. With the progress of spore encapsulation, the tyrocidine production migrated from the soluble fraction into the forespore, terminating with the separation of forespores from the sporangium membrane. The resulting concentration of antibiotic in the forespore may indicate its function in sporulation, the nature of which, however, was not explored."} {"id": "PMID:167032", "title": "\"Ultramicroinjection\" of macromolecules or small particles into animal cells. A new technique based on virus-induced cell fusion.", "content": "A new method is described for the introduction of macromolecules and small particles into animal cells. The first step in this procedure is the trapping of particles in ghosts of human erythrocytes. This is achieved by the gradual hemolysis of erythrocytes in the presence of the particles to be trapped. The second step is the Sendai virus-induced fusion of the ghosts containing the particles with cells. By this method, ferritin and latex spheres (diameter 0.1 mum) have been \"injected\" into cells.", "contents": "\"Ultramicroinjection\" of macromolecules or small particles into animal cells. A new technique based on virus-induced cell fusion. A new method is described for the introduction of macromolecules and small particles into animal cells. The first step in this procedure is the trapping of particles in ghosts of human erythrocytes. This is achieved by the gradual hemolysis of erythrocytes in the presence of the particles to be trapped. The second step is the Sendai virus-induced fusion of the ghosts containing the particles with cells. By this method, ferritin and latex spheres (diameter 0.1 mum) have been \"injected\" into cells."} {"id": "PMID:167033", "title": "An ultracytochemical study of the respiratory potency, integrity, and fate of the sea urchin sperm mitochondria during early embryogenesis.", "content": "Cytochrome oxidase activity via cytochrome c, as demonstrated by the diaminobenzidine procedure, has been employed in this electron microscope cytochemical study to determine the respiratory potency, integrity and fate of the Arbacia sperm mitochondrion at fertilization and during early embryogenesis. The sperm mitochondrion remained intact and was intensely positive for cytochrome oxidase activity both during and after penetration into the egg. The mitochondrion remained highly reactive throughout zygote formation, up to the eight-cell stage. The sperm mitochondrion formed many projections and buds in the cytoplasm of immature oocytes, monospermic and polyspermic eggs, and in blastomeres. At all stages of early embryogenesis, close juxtaposition and structural contact were observed between the highly reactive sperm mitochondrion and the less reactive egg mitochondria. The results suggest that following fertilization the mitochondrion of the sea urchin spermatozoon retains some degree of metabolic autonomy within the ooplasm. The structural integrity of the paternal mitochondrion is maintained along with a functional respiratory enzyme system (cytochrome c-a3). The hypothesis that the fertilizing sperm mitochondrion may have some relevance to sea urchin development is discussed.", "contents": "An ultracytochemical study of the respiratory potency, integrity, and fate of the sea urchin sperm mitochondria during early embryogenesis. Cytochrome oxidase activity via cytochrome c, as demonstrated by the diaminobenzidine procedure, has been employed in this electron microscope cytochemical study to determine the respiratory potency, integrity and fate of the Arbacia sperm mitochondrion at fertilization and during early embryogenesis. The sperm mitochondrion remained intact and was intensely positive for cytochrome oxidase activity both during and after penetration into the egg. The mitochondrion remained highly reactive throughout zygote formation, up to the eight-cell stage. The sperm mitochondrion formed many projections and buds in the cytoplasm of immature oocytes, monospermic and polyspermic eggs, and in blastomeres. At all stages of early embryogenesis, close juxtaposition and structural contact were observed between the highly reactive sperm mitochondrion and the less reactive egg mitochondria. The results suggest that following fertilization the mitochondrion of the sea urchin spermatozoon retains some degree of metabolic autonomy within the ooplasm. The structural integrity of the paternal mitochondrion is maintained along with a functional respiratory enzyme system (cytochrome c-a3). The hypothesis that the fertilizing sperm mitochondrion may have some relevance to sea urchin development is discussed."} {"id": "PMID:167034", "title": "Antagonism by dibutyryl adenosine cyclic 3',5'-monophosphate and testololactone of concanavalin A capping.", "content": "Exposure of CHO-K1 cells in vitro to dibutyryl adenosine cyclic 3',5'-monophosphate (DBcAMP) plus testololactone produces a rapid, reversible antagonism of ligand-induced collection of initially dispersed concanavalin A (Con A) binding sites into a caplike mass. Morphologically, as Con A capping occurs, the cells become less spread and then round completely. With prolonged Con A exposure, cells cultured in either the absence or the presence of DBcAMP plus testololactone cap and round. Capping is blocked by cold treatment and respiratory inhibitors. Colcemid at concentrations greater than 1 muM promotes both Con A capping and cell rounding. Cytochalasin B at similar concentrations inhibits both capping and cell rounding. Treatment of cells with Con A has little effect on intracellular cAMP concentration. Possible mechanisms by which cAMP may modulate the movement of Con A binding sites are discussed.", "contents": "Antagonism by dibutyryl adenosine cyclic 3',5'-monophosphate and testololactone of concanavalin A capping. Exposure of CHO-K1 cells in vitro to dibutyryl adenosine cyclic 3',5'-monophosphate (DBcAMP) plus testololactone produces a rapid, reversible antagonism of ligand-induced collection of initially dispersed concanavalin A (Con A) binding sites into a caplike mass. Morphologically, as Con A capping occurs, the cells become less spread and then round completely. With prolonged Con A exposure, cells cultured in either the absence or the presence of DBcAMP plus testololactone cap and round. Capping is blocked by cold treatment and respiratory inhibitors. Colcemid at concentrations greater than 1 muM promotes both Con A capping and cell rounding. Cytochalasin B at similar concentrations inhibits both capping and cell rounding. Treatment of cells with Con A has little effect on intracellular cAMP concentration. Possible mechanisms by which cAMP may modulate the movement of Con A binding sites are discussed."} {"id": "PMID:167035", "title": "Galactose and glucose metabolism in galactokinase deficient, galactose-1-P-uridyl transferase deficient and normal human fibroblasts.", "content": "Despite the genetic interruption of the Leloir pathway both galactosemic patients and galactosemic fibroblasts can convert galactose to CO2 and TCA precipitable products, although at less than the normal rate. These observations stimulated investigations into the identity of the alternative metabolic routes which allows for galactose metabolism in the absence of in vitro galactose-1-P-uridyl transferase. Four lines of galactosemic cells, each without detectable gal-transferase, produced 14CO2 from [1-14C]-galactose (0.094 mumoles in 20 cc of medium) at approximately 39% +/- 16% the rate of transferase positive cells over a 48-hour period. However, galactokinase deficient fibroblasts produced 14CO2 and TCA precipitable products from [1-14C]-galactose or [U-14C]-galactose at only 3% to 9% the rate of normal fibroblasts. Therefore it seems likely that gal-transferase deficient fibroblasts must first synthesize galactose-1-P for further metabolism of galactose.", "contents": "Galactose and glucose metabolism in galactokinase deficient, galactose-1-P-uridyl transferase deficient and normal human fibroblasts. Despite the genetic interruption of the Leloir pathway both galactosemic patients and galactosemic fibroblasts can convert galactose to CO2 and TCA precipitable products, although at less than the normal rate. These observations stimulated investigations into the identity of the alternative metabolic routes which allows for galactose metabolism in the absence of in vitro galactose-1-P-uridyl transferase. Four lines of galactosemic cells, each without detectable gal-transferase, produced 14CO2 from [1-14C]-galactose (0.094 mumoles in 20 cc of medium) at approximately 39% +/- 16% the rate of transferase positive cells over a 48-hour period. However, galactokinase deficient fibroblasts produced 14CO2 and TCA precipitable products from [1-14C]-galactose or [U-14C]-galactose at only 3% to 9% the rate of normal fibroblasts. Therefore it seems likely that gal-transferase deficient fibroblasts must first synthesize galactose-1-P for further metabolism of galactose."} {"id": "PMID:167036", "title": "Somatic genetic analysis of cyclic AMP action: selection of unresponsive mutants.", "content": "Dibutyryl cyclic AMP and theophylline kill S49.1 mouse lymphoma tissue culture cells. When cells are grown in soft agar with these drugs, the few clones that survive are resistant to cytolysis. The rate of mutation to resistance is 1-3 times 10-7/cell/generation in both diploid and tetraploid cells. The incidence of mutants is increased by treatment with a chemical mutagen, ICR 191. The mutation is consistently associated with greatly reduced or absent cytoplasmic cyclic AMP binding protein. These results suggest that a somatic mutation leads to a defect of the protein kinase regulatory subunit and that activity of this kinase is required for induction of cell death by cyclic AMP.", "contents": "Somatic genetic analysis of cyclic AMP action: selection of unresponsive mutants. Dibutyryl cyclic AMP and theophylline kill S49.1 mouse lymphoma tissue culture cells. When cells are grown in soft agar with these drugs, the few clones that survive are resistant to cytolysis. The rate of mutation to resistance is 1-3 times 10-7/cell/generation in both diploid and tetraploid cells. The incidence of mutants is increased by treatment with a chemical mutagen, ICR 191. The mutation is consistently associated with greatly reduced or absent cytoplasmic cyclic AMP binding protein. These results suggest that a somatic mutation leads to a defect of the protein kinase regulatory subunit and that activity of this kinase is required for induction of cell death by cyclic AMP."} {"id": "PMID:167037", "title": "Somatic genetic analysis of cyclic AMP action: characterization of unresponsive mutants.", "content": "N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate kills cultured mouse lymphosarcoma cells, but not resistant mutants derived by a single-step clonal selection. Resistant clones lack the cyclic AMP binding proteins present in wild type, cyclic AMP sensitive clones. Both endogenous cyclic AMP, accumulated in response to isoproterenol or cholera toxin, and exogenous dibutyryl cyclic AMP induce cyclic AMP phosphodiesterase, slow growth, and eventually kill wild type cells. In the resistant mutants, however, the endogenous and exogenous cyclic nucleotides appear to be completely inactive. These results indicate that an intracellular receptor for cyclic AMP, previously shown to be associated with a cyclic AMP-dependent protein kinase, mediates cyclic AMP's regulation of growth and phosphodiesterase synthesis.", "contents": "Somatic genetic analysis of cyclic AMP action: characterization of unresponsive mutants. N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate kills cultured mouse lymphosarcoma cells, but not resistant mutants derived by a single-step clonal selection. Resistant clones lack the cyclic AMP binding proteins present in wild type, cyclic AMP sensitive clones. Both endogenous cyclic AMP, accumulated in response to isoproterenol or cholera toxin, and exogenous dibutyryl cyclic AMP induce cyclic AMP phosphodiesterase, slow growth, and eventually kill wild type cells. In the resistant mutants, however, the endogenous and exogenous cyclic nucleotides appear to be completely inactive. These results indicate that an intracellular receptor for cyclic AMP, previously shown to be associated with a cyclic AMP-dependent protein kinase, mediates cyclic AMP's regulation of growth and phosphodiesterase synthesis."} {"id": "PMID:167038", "title": "The relation of endogenous adenosine cyclic 3':5'-monophosphate to the antagonistic effects of adenosine and colchicine on cell shape.", "content": "Adenosine and colchicine have antagonistic effects on cell shape. When Chinese Hamster lung fibroblasts (CHE36-6) or SV40 transformed 3T3 (SV3T3) cells are incubated with colchicine (1 muM) for one hour at 37 degrees C, they round up into spheres with short spikes. Cells treated with adenosine (1 muM-minus 4 mM) for one hour become refractile and develop spindly processes. However, when the two compounds are added simultaneously, the characteristic responses to either drug are abolished and the cells appear normal. The counteraction is specific for adenine and its derivatives, adenosine being the most effective of the compounds we tested. Accumulation of colchicine or adenosine is not altered significantly by the presence of the other drug, ruling out decreases in uptake as the basis of the mutual antagonism. The morphological changes can be observed under conditions where there are no changes in intracellular cAMP levels (such as incubation with low concentrations of adenosine or cordycepin, an adenosine analog that cannot be directly converted to cAMP). Colchicine does not alter cAMP content of control or adenosine-treated cells. These data show that adenine compounds have potent effects on cell shape, and the antagonistic effects of adenosine and colchicine on cell shape are not mediated through changes in intracellular cAMP levels.", "contents": "The relation of endogenous adenosine cyclic 3':5'-monophosphate to the antagonistic effects of adenosine and colchicine on cell shape. Adenosine and colchicine have antagonistic effects on cell shape. When Chinese Hamster lung fibroblasts (CHE36-6) or SV40 transformed 3T3 (SV3T3) cells are incubated with colchicine (1 muM) for one hour at 37 degrees C, they round up into spheres with short spikes. Cells treated with adenosine (1 muM-minus 4 mM) for one hour become refractile and develop spindly processes. However, when the two compounds are added simultaneously, the characteristic responses to either drug are abolished and the cells appear normal. The counteraction is specific for adenine and its derivatives, adenosine being the most effective of the compounds we tested. Accumulation of colchicine or adenosine is not altered significantly by the presence of the other drug, ruling out decreases in uptake as the basis of the mutual antagonism. The morphological changes can be observed under conditions where there are no changes in intracellular cAMP levels (such as incubation with low concentrations of adenosine or cordycepin, an adenosine analog that cannot be directly converted to cAMP). Colchicine does not alter cAMP content of control or adenosine-treated cells. These data show that adenine compounds have potent effects on cell shape, and the antagonistic effects of adenosine and colchicine on cell shape are not mediated through changes in intracellular cAMP levels."} {"id": "PMID:167039", "title": "Difference in transport of leucine in attached and suspended 3T3 cells.", "content": "3T3 cells in subconfluent culture take up leucine through a transport system which has a relatively high affinity for leucine (M system). When the culture becomes confluent, the M system is turned off and leucine is transported by another system which has a low affinity for leucine (S system). The M system is reactivated by transferring the cells into subconfluent cultures. In suspension cultures 3T3 cells, initiated from confluent cultures, the M system is not activated and leucine is transported by the S system. In cells suspended from subconfluent culture, the M system continues to operate at a high level for four hours and then is gradually turned off. Tumor virus transformed 3T3 cells (SV3T3 and Py3T3) grow quite well in suspension culture and transport leucine both in monolayer and suspension through a high affinity system, with a high Vmax value. A derivative of 3T3, 3T3/41, which grows in suspension much more slowly than tumor virus transformed 3T3 cells, also takes up leucine through a high affinity transport system both in monolayer and suspension but its Vmax value is lower than that of the transformed cells.", "contents": "Difference in transport of leucine in attached and suspended 3T3 cells. 3T3 cells in subconfluent culture take up leucine through a transport system which has a relatively high affinity for leucine (M system). When the culture becomes confluent, the M system is turned off and leucine is transported by another system which has a low affinity for leucine (S system). The M system is reactivated by transferring the cells into subconfluent cultures. In suspension cultures 3T3 cells, initiated from confluent cultures, the M system is not activated and leucine is transported by the S system. In cells suspended from subconfluent culture, the M system continues to operate at a high level for four hours and then is gradually turned off. Tumor virus transformed 3T3 cells (SV3T3 and Py3T3) grow quite well in suspension culture and transport leucine both in monolayer and suspension through a high affinity system, with a high Vmax value. A derivative of 3T3, 3T3/41, which grows in suspension much more slowly than tumor virus transformed 3T3 cells, also takes up leucine through a high affinity transport system both in monolayer and suspension but its Vmax value is lower than that of the transformed cells."} {"id": "PMID:167040", "title": "Effects of discrete nuclear u.v-microbeam irradiation on herpes virus and SV40 infection.", "content": "The requirement for a nucleolus in the expression of structural genes of nuclear viruses was examined by means of experiments in which the nucleolus or other parts of the nucleus was inactivated by a microbean of unltraviolet light. These experiments showed that the expression of such genes is not dependent on cucleolar function. This conclusion is discussed in the light of previous experiments in which similar inactiviation of nucleolus was shown to prevent the expression of cellular structural genes.", "contents": "Effects of discrete nuclear u.v-microbeam irradiation on herpes virus and SV40 infection. The requirement for a nucleolus in the expression of structural genes of nuclear viruses was examined by means of experiments in which the nucleolus or other parts of the nucleus was inactivated by a microbean of unltraviolet light. These experiments showed that the expression of such genes is not dependent on cucleolar function. This conclusion is discussed in the light of previous experiments in which similar inactiviation of nucleolus was shown to prevent the expression of cellular structural genes."} {"id": "PMID:167041", "title": "The binding of the mucoprotein from gastric mucus to cells in tissue culture and the inhibition of cell adhesion.", "content": "The mucoprotein, which is responsible for the formation of gastric mucous gel in pig, has been shown to bind equally well to suspensions of baby hamster kidney cells, polyoma-virus-transformed baby hamster kidney cells and HeLa cells. The binding of the mucoprotein to the cells is dependent on Ca 2", "contents": "The binding of the mucoprotein from gastric mucus to cells in tissue culture and the inhibition of cell adhesion. The mucoprotein, which is responsible for the formation of gastric mucous gel in pig, has been shown to bind equally well to suspensions of baby hamster kidney cells, polyoma-virus-transformed baby hamster kidney cells and HeLa cells. The binding of the mucoprotein to the cells is dependent on Ca 2"} {"id": "PMID:167042", "title": "Phase-contrast and electron-microscopic observations on a membranous complex in primary spermatocytes of the mouse.", "content": "A prominent cytoplasmic inclusion present in living mouse primary spermatocytes has been observed by both light and electron microscopy. It began to form at prometaphase and continued to increase in thickness and length as the cells developed. By metaphase it was a distinct sausage-shaped boundary that enclosed a portion of the cytoplasm between the spindle and the cell membrane. At the end of metaphase, the inclusion reached its maximum length. At telophase, it was divided between the daughter secondaries. The inclusion persisted as a circular contour in the interphase secondary spermatocyte. Electron microscopy of the same cultured cells that were previously observed with light microscopy revealed that the inclusion was a distinctive formation of membranes. It consisted of agranular cisternae and vesicles, and was therefore a membranous complex. Many of the smaller vesicles in the membranous complex resembled those found in the spindle. The cisternae in the membranous complex were identical to the cisternal endoplasmic reticulum of interphase primary spermatocytes. Nevertheless, the organization of vesicles and cisternae into the membranous complex was unique for the primaries in division stages, since such an organization was not present in their interphase stages.", "contents": "Phase-contrast and electron-microscopic observations on a membranous complex in primary spermatocytes of the mouse. A prominent cytoplasmic inclusion present in living mouse primary spermatocytes has been observed by both light and electron microscopy. It began to form at prometaphase and continued to increase in thickness and length as the cells developed. By metaphase it was a distinct sausage-shaped boundary that enclosed a portion of the cytoplasm between the spindle and the cell membrane. At the end of metaphase, the inclusion reached its maximum length. At telophase, it was divided between the daughter secondaries. The inclusion persisted as a circular contour in the interphase secondary spermatocyte. Electron microscopy of the same cultured cells that were previously observed with light microscopy revealed that the inclusion was a distinctive formation of membranes. It consisted of agranular cisternae and vesicles, and was therefore a membranous complex. Many of the smaller vesicles in the membranous complex resembled those found in the spindle. The cisternae in the membranous complex were identical to the cisternal endoplasmic reticulum of interphase primary spermatocytes. Nevertheless, the organization of vesicles and cisternae into the membranous complex was unique for the primaries in division stages, since such an organization was not present in their interphase stages."} {"id": "PMID:167046", "title": "Trimethylsilylation of penicillic acid and patulin, and the stability of the products.", "content": "Penicillic acid and patulin have been effectively silylated by N,O-bis(trimethylsilyl)acetamide, alone or with trimethylchlorosilane in benzene. The silylation products are stable, if stored under refrigeration, for at least 15 days.", "contents": "Trimethylsilylation of penicillic acid and patulin, and the stability of the products. Penicillic acid and patulin have been effectively silylated by N,O-bis(trimethylsilyl)acetamide, alone or with trimethylchlorosilane in benzene. The silylation products are stable, if stored under refrigeration, for at least 15 days."} {"id": "PMID:167047", "title": "Determination of penicillic acid and patulin by gas-liquid chromatography with an electron-capture detector.", "content": "Quantitative and concurrent determinations of penicillic acid and patulin have been achieved after separation of these compounds, as their trimethylsilyl derivatives, by gas-liquid chromatography with electron-capture detection and a column of 10% of DC-200 plus 15% of QF-1 on Gas-Chrom Q; the minimum determinable amounts of penicillic acid and patulin were 0.05 and 0.1 ng, respectively. The procedure devised for determining these compounds in grain involves extraction with solvents, followed by further clean-up by thin-layer chromatography; the detection limit of this procedure is about 0.02 ppm, and recovery at the level of 0.05 ppm is about 90%. The significant separation of penicillic acid and patulin produced in moldy rice is demonstrated on the gas chromatograms, and this makes possible a micro-assay for these toxic compounds in contaminated grain.", "contents": "Determination of penicillic acid and patulin by gas-liquid chromatography with an electron-capture detector. Quantitative and concurrent determinations of penicillic acid and patulin have been achieved after separation of these compounds, as their trimethylsilyl derivatives, by gas-liquid chromatography with electron-capture detection and a column of 10% of DC-200 plus 15% of QF-1 on Gas-Chrom Q; the minimum determinable amounts of penicillic acid and patulin were 0.05 and 0.1 ng, respectively. The procedure devised for determining these compounds in grain involves extraction with solvents, followed by further clean-up by thin-layer chromatography; the detection limit of this procedure is about 0.02 ppm, and recovery at the level of 0.05 ppm is about 90%. The significant separation of penicillic acid and patulin produced in moldy rice is demonstrated on the gas chromatograms, and this makes possible a micro-assay for these toxic compounds in contaminated grain."} {"id": "PMID:167048", "title": "Inorganic saltsin the fluorometric detection of presticides.", "content": "A method is described for the detection and quantification of pesticides on silica gel ghromatograms by in situ fluorometry. Simple inorganic salts are used to induce fluorescence in a number of pesticidal compounds. Intensified fluorescence is shown for one naturally fluorescent pesticide. Spectral data and instrumental limits of detection are given.", "contents": "Inorganic saltsin the fluorometric detection of presticides. A method is described for the detection and quantification of pesticides on silica gel ghromatograms by in situ fluorometry. Simple inorganic salts are used to induce fluorescence in a number of pesticidal compounds. Intensified fluorescence is shown for one naturally fluorescent pesticide. Spectral data and instrumental limits of detection are given."} {"id": "PMID:167050", "title": "Chromatographic-fluorometric analysis of antileprotic sulfones.", "content": "Modifications to the power supply system of a spectrophotofluorometer are described. These modifications stabilize the output of the xenon are lamp and permit the determination of nanogram quantities of antileprotic sulfones. The sulfones are removed from plasma by a single extraction with ethyl acetate, then separated by high-pressure liquid chromatography on silica, and detected in the effluent by their fluorescence. The method is specific, rapid, and reproducible.", "contents": "Chromatographic-fluorometric analysis of antileprotic sulfones. Modifications to the power supply system of a spectrophotofluorometer are described. These modifications stabilize the output of the xenon are lamp and permit the determination of nanogram quantities of antileprotic sulfones. The sulfones are removed from plasma by a single extraction with ethyl acetate, then separated by high-pressure liquid chromatography on silica, and detected in the effluent by their fluorescence. The method is specific, rapid, and reproducible."} {"id": "PMID:167051", "title": "Rapid identification of amino acid derivatives from the sequenator.", "content": "A simple procedure is described for converting thiazolinones, from the protein sequenator, to the more stable phenylthiohydantoins without using the conventional HCI conversion procedure. The thiazolinones are applied to a silica gel plate and converted to phenylthiohydantoins by heating at 140 for 5-10 min, in the presence of heptafluorobutyric acid, prior to chromatography. After chromatography, measurements of the yields of the derivatives on the plate can be made with a variable-wave-length thin-layer chromatography scanner. This is shown to be a useful adjunct for identifications.", "contents": "Rapid identification of amino acid derivatives from the sequenator. A simple procedure is described for converting thiazolinones, from the protein sequenator, to the more stable phenylthiohydantoins without using the conventional HCI conversion procedure. The thiazolinones are applied to a silica gel plate and converted to phenylthiohydantoins by heating at 140 for 5-10 min, in the presence of heptafluorobutyric acid, prior to chromatography. After chromatography, measurements of the yields of the derivatives on the plate can be made with a variable-wave-length thin-layer chromatography scanner. This is shown to be a useful adjunct for identifications."} {"id": "PMID:167052", "title": "Analysis for organophosphorus insecticides and metabolites.", "content": "Extraction and cleanup methods used for the analysis of organophosphate pesticides are similar to those used for chlorinated hydrocarbons but differ in some important details. Many organophosphates are lost during extraction of acetonitrile solutions containing organophosphates with petroleum ether; dichloromethane is substituted. Also, cleanup by column chromatography on mixed adsorbents containing charcoal results in better recoveries than can be obtained on Florisil alone. The detectors used for measurement of organophosphates by GLC are almost unique for this group of compounds. TLC is very useful for confirming the identities of the compounds, and several promising optical methods are available for their measurement. Methods for the analysis of metabolites of this group are basically similar, since all organophosphates undergo dealkylation reactions and cleavage of the acid anhydride bond. However, measurement of the polar group which is removed during phosphorylation or other reactions involving cleavage of the acid anhydride bond is a problem unique for each compound.", "contents": "Analysis for organophosphorus insecticides and metabolites. Extraction and cleanup methods used for the analysis of organophosphate pesticides are similar to those used for chlorinated hydrocarbons but differ in some important details. Many organophosphates are lost during extraction of acetonitrile solutions containing organophosphates with petroleum ether; dichloromethane is substituted. Also, cleanup by column chromatography on mixed adsorbents containing charcoal results in better recoveries than can be obtained on Florisil alone. The detectors used for measurement of organophosphates by GLC are almost unique for this group of compounds. TLC is very useful for confirming the identities of the compounds, and several promising optical methods are available for their measurement. Methods for the analysis of metabolites of this group are basically similar, since all organophosphates undergo dealkylation reactions and cleavage of the acid anhydride bond. However, measurement of the polar group which is removed during phosphorylation or other reactions involving cleavage of the acid anhydride bond is a problem unique for each compound."} {"id": "PMID:167053", "title": "Analysis of fumigants and fumigant residues.", "content": "The terms fumigant and fumigant residue are defined. Interrelationships between physically and chemically bound residues, storage environments, nature of the substrate and other influencing factors are outlined. Analytical methods include polarography by DME and RPE, titrimetry, spectrophotometry, and GC with microthermal conductivity, hydrogen flame ionization, electron capture, microcoulometric, thermionic, and flame photometric detector systems, with backup by enzymatic, radiometric, NAA and X-ray flourescence methods. Various aspects are illustrated with different fumigants used commercially. Supplementary methods to extend the power and usefulness of analytical methods in fumigant research are indicated.", "contents": "Analysis of fumigants and fumigant residues. The terms fumigant and fumigant residue are defined. Interrelationships between physically and chemically bound residues, storage environments, nature of the substrate and other influencing factors are outlined. Analytical methods include polarography by DME and RPE, titrimetry, spectrophotometry, and GC with microthermal conductivity, hydrogen flame ionization, electron capture, microcoulometric, thermionic, and flame photometric detector systems, with backup by enzymatic, radiometric, NAA and X-ray flourescence methods. Various aspects are illustrated with different fumigants used commercially. Supplementary methods to extend the power and usefulness of analytical methods in fumigant research are indicated."} {"id": "PMID:167054", "title": "Control and localization of rat adrenal cyclic guanosine 3', 5'-monophosphate. Comparison with adrenal cyclic adenosine 3', 5'-monophosphate.", "content": "Cyclic AMP and cyclic GMP were measured in rat adrenal glands after either hypophysectomy alone or after hypophysectomy and treatment with ACTH. Adrenal cyclic GMP levels rise in acutely hypophysectomized rats to a maximum at 1 h of approximately 200% of control levels; there is a return to base line at 4-12 h after hypophysectomy. In contrast, adrenal cyclic AMP falls immediately to about 50% of control levels after hypophysectomy and remains at approximately 1 pmol per mg tissue. Doses of ACTH beyond the physiological range markedly suppress adrenal cyclic GMP while producing a 50-fold or greater rise in cyclic AMP in hypophysectomized rats. This pattern of adrenal cyclic GMP rise was unchanged in acutely hypophysectomized animals treated with desamethasone. N-6-2'-0 dibutyryl cyclic AMP acted similarly to the effect of ACTH in bringing about a suppression of adrenal cyclic GMP levels. Physiological i.v. pulse doses of ACTH produced a rapid dose related increase in adrenal cyclic GMP. In vitro incubation of quartered adrenal pairs with 500 mU ACTH produced elevated cyclic AMP levels and suppression of cyclic GMP. Whereas adrenal cyclic AMP fell rapidly to 50% of control levels after hypophysectomy and remained at about 1 pmol per mg tissue for 7 days, adrenal cyclic GMP showed a biphasic rhythm in long-term hypophysectomized animals. After an initial peak at 1 h after hypophysectomy, adrenal cyclic GMP declined to baseline at 4-12 h but thereafter progressively rose with time, eventually reaching levels over 1 pmol per mg tissue. Fluorescent immunocytochemical staining of rat adrenal zona fasciculata showed cyclic AMP largely confined to cytoplasmic elements with little fluorescence contained in nuclei. In constant, cyclic GMP was found discretely positioned in nuclei with prominent fluorescence in nucleoli in addition to cytoplasmic localization. It is concluded that in hypophysectomized rats ACTH, either directly or in conjunction with altertion of adrenal cyclic AMP, appears to be one factor which regulates adrenal cyclic GMP. The direction of cyclic GMP change and the different subcellular localization of the nucleotides suggest divergent roles for cyclic AMP and cyclic GMP in adrenocortical function. Furthermore, our observations suggest a role for adrenal cyclic GMP in nuclear directed events.", "contents": "Control and localization of rat adrenal cyclic guanosine 3', 5'-monophosphate. Comparison with adrenal cyclic adenosine 3', 5'-monophosphate. Cyclic AMP and cyclic GMP were measured in rat adrenal glands after either hypophysectomy alone or after hypophysectomy and treatment with ACTH. Adrenal cyclic GMP levels rise in acutely hypophysectomized rats to a maximum at 1 h of approximately 200% of control levels; there is a return to base line at 4-12 h after hypophysectomy. In contrast, adrenal cyclic AMP falls immediately to about 50% of control levels after hypophysectomy and remains at approximately 1 pmol per mg tissue. Doses of ACTH beyond the physiological range markedly suppress adrenal cyclic GMP while producing a 50-fold or greater rise in cyclic AMP in hypophysectomized rats. This pattern of adrenal cyclic GMP rise was unchanged in acutely hypophysectomized animals treated with desamethasone. N-6-2'-0 dibutyryl cyclic AMP acted similarly to the effect of ACTH in bringing about a suppression of adrenal cyclic GMP levels. Physiological i.v. pulse doses of ACTH produced a rapid dose related increase in adrenal cyclic GMP. In vitro incubation of quartered adrenal pairs with 500 mU ACTH produced elevated cyclic AMP levels and suppression of cyclic GMP. Whereas adrenal cyclic AMP fell rapidly to 50% of control levels after hypophysectomy and remained at about 1 pmol per mg tissue for 7 days, adrenal cyclic GMP showed a biphasic rhythm in long-term hypophysectomized animals. After an initial peak at 1 h after hypophysectomy, adrenal cyclic GMP declined to baseline at 4-12 h but thereafter progressively rose with time, eventually reaching levels over 1 pmol per mg tissue. Fluorescent immunocytochemical staining of rat adrenal zona fasciculata showed cyclic AMP largely confined to cytoplasmic elements with little fluorescence contained in nuclei. In constant, cyclic GMP was found discretely positioned in nuclei with prominent fluorescence in nucleoli in addition to cytoplasmic localization. It is concluded that in hypophysectomized rats ACTH, either directly or in conjunction with altertion of adrenal cyclic AMP, appears to be one factor which regulates adrenal cyclic GMP. The direction of cyclic GMP change and the different subcellular localization of the nucleotides suggest divergent roles for cyclic AMP and cyclic GMP in adrenocortical function. Furthermore, our observations suggest a role for adrenal cyclic GMP in nuclear directed events."} {"id": "PMID:167062", "title": "Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle.", "content": "Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.", "contents": "Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle. Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro."} {"id": "PMID:167063", "title": "Adrenal responsiveness in lactating holstein cows.", "content": "Ten Holstein cows, in second to fifth lactation, received 200 IU adrenocorticotrophin at approximately 4, 8, 16, 24, 32, and 40 wk of lactation. Blood samples were collected from indwelling jugular catheters at -60 and 0 min pre-injection and at 2, 6, 10, 15, 20, 30, 45, 60, 120, 180, 240, 360, 540, and 720 min postinjection. Post-injection concentrations of glucocorticoids were influenced by milk yield, stage of lactation, age, and mean environmental temperature but not by pre-injection concentration of glucocorticoids or days pregnant. As milk yield, cow age, and daily temperature (range 6.4 to 26.9 C) increased, glucocorticoid response decreased whereas it increased with advancing stage of lactation. Curves of adrenal response for the six injection times during lactation were not parallel, and average response adjusted for significant independent variables increased roughly in linear fashion from 15 to 53 ng/ml between 4 and 40 wk of lactation. Adrenal responsiveness was less in cows injected on days when temperatures were above 21.1 C than in those injected below this temperature. There was no evidence that adrenal function or milk production was altered in high producing cows at higher environmental temperatures differently from in low producing cows. The change in adrenal function during advancing lactation was not associated with pre-treatment peripheral plasma glucocorticoid concentrations which did not change. There appears to be a well mainained adrenal potential and sustained adrenocortical activity throughout lactation.", "contents": "Adrenal responsiveness in lactating holstein cows. Ten Holstein cows, in second to fifth lactation, received 200 IU adrenocorticotrophin at approximately 4, 8, 16, 24, 32, and 40 wk of lactation. Blood samples were collected from indwelling jugular catheters at -60 and 0 min pre-injection and at 2, 6, 10, 15, 20, 30, 45, 60, 120, 180, 240, 360, 540, and 720 min postinjection. Post-injection concentrations of glucocorticoids were influenced by milk yield, stage of lactation, age, and mean environmental temperature but not by pre-injection concentration of glucocorticoids or days pregnant. As milk yield, cow age, and daily temperature (range 6.4 to 26.9 C) increased, glucocorticoid response decreased whereas it increased with advancing stage of lactation. Curves of adrenal response for the six injection times during lactation were not parallel, and average response adjusted for significant independent variables increased roughly in linear fashion from 15 to 53 ng/ml between 4 and 40 wk of lactation. Adrenal responsiveness was less in cows injected on days when temperatures were above 21.1 C than in those injected below this temperature. There was no evidence that adrenal function or milk production was altered in high producing cows at higher environmental temperatures differently from in low producing cows. The change in adrenal function during advancing lactation was not associated with pre-treatment peripheral plasma glucocorticoid concentrations which did not change. There appears to be a well mainained adrenal potential and sustained adrenocortical activity throughout lactation."} {"id": "PMID:167066", "title": "Transport of dietary cholesterol into blood and milk of the goat.", "content": "Position 4 labeled carbon-14 cholesterol was placed in abomasums (stomachs) of two lactating goats. Blood and milk samples were collected from the animals for 5 to 13 days. Specific activities of cholesterol and cholesteryl esters in various fractions of blood serum and milk were determined to reveal pathways by which dietary cholesterol enters milk. Results with the two animals showed similar trends. Within 24 h both cholesterol and cholesteryl esters of the three principal serum lipoproteins of the goat were labeled, and this labeling persisted in substantial degree for the 13-day experiment. Specific acities for cholesteryl esters in milk fat globules exhibited several remarkable attributes: they fluctuated in intensity with a 3-to 4-day cycle reaching a maximum at 7 to 8 days after tracer injection; they exceeded cholesteryl ester specific activity in the skim milk by an order of magnitude; and at their maximum they exceeded all specific activities for serum components. The results of this investigation exemplify the ease with which dietary cholesterol enters and crosses membranes in the animal body.", "contents": "Transport of dietary cholesterol into blood and milk of the goat. Position 4 labeled carbon-14 cholesterol was placed in abomasums (stomachs) of two lactating goats. Blood and milk samples were collected from the animals for 5 to 13 days. Specific activities of cholesterol and cholesteryl esters in various fractions of blood serum and milk were determined to reveal pathways by which dietary cholesterol enters milk. Results with the two animals showed similar trends. Within 24 h both cholesterol and cholesteryl esters of the three principal serum lipoproteins of the goat were labeled, and this labeling persisted in substantial degree for the 13-day experiment. Specific acities for cholesteryl esters in milk fat globules exhibited several remarkable attributes: they fluctuated in intensity with a 3-to 4-day cycle reaching a maximum at 7 to 8 days after tracer injection; they exceeded cholesteryl ester specific activity in the skim milk by an order of magnitude; and at their maximum they exceeded all specific activities for serum components. The results of this investigation exemplify the ease with which dietary cholesterol enters and crosses membranes in the animal body."} {"id": "PMID:167067", "title": "Origin of cyclic adenosine monophosphate in saliva.", "content": "The level of cyclic adenosine monophosphate (AMP) in duct saliva from the dog submandibular gland was increased after cyclic AMP was administered intravenously in vivo. Isoproterenol increased the level of cyclic AMP in plasma and saliva in vivo and in salivary gland slices in vitro, but increased the level only slightly in saliva in a prefused dog submaxillary gland.", "contents": "Origin of cyclic adenosine monophosphate in saliva. The level of cyclic adenosine monophosphate (AMP) in duct saliva from the dog submandibular gland was increased after cyclic AMP was administered intravenously in vivo. Isoproterenol increased the level of cyclic AMP in plasma and saliva in vivo and in salivary gland slices in vitro, but increased the level only slightly in saliva in a prefused dog submaxillary gland."} {"id": "PMID:167077", "title": "A procedure for removing red cells and dead cells from lymphoid cell suspensions.", "content": "A procedure is described for simultaneously removing red cells and dead cells from lymphoid cell suspensions, based on the observation that when populations of lymphoid cells are centrifuged on a mixture of Isopaque/Ficoll, dead cells and red cells sediment whereas viable cells float. The technique very efficiently removed red cells from a wide range of lymphoid cell suspensions and eliminated lymphocytes killed by mechanical stress, by antibody and complement and by prolonged tissue culture. The depletion of red cells was greater than 99% and the recovery of viable lymphocytes usually greater than 90%, the resulting cell suspensions being around 95-100% viable. The immunological activity of B cells, helper T cells and cytotoxic T cells virtually unimpaired by the separation procedure.", "contents": "A procedure for removing red cells and dead cells from lymphoid cell suspensions. A procedure is described for simultaneously removing red cells and dead cells from lymphoid cell suspensions, based on the observation that when populations of lymphoid cells are centrifuged on a mixture of Isopaque/Ficoll, dead cells and red cells sediment whereas viable cells float. The technique very efficiently removed red cells from a wide range of lymphoid cell suspensions and eliminated lymphocytes killed by mechanical stress, by antibody and complement and by prolonged tissue culture. The depletion of red cells was greater than 99% and the recovery of viable lymphocytes usually greater than 90%, the resulting cell suspensions being around 95-100% viable. The immunological activity of B cells, helper T cells and cytotoxic T cells virtually unimpaired by the separation procedure."} {"id": "PMID:167078", "title": "Epidermal synthesis of prostaglandins and their effect on levels of cyclic adenosine 3', 5'monophosphate.", "content": "Extracts of guinea-pig and human skin epidermis were analyzed for prostaglandins PGE1, E2, and F2alpha by radioimmunoassy, and found to contain a total of 62.0 (guinea pig) and 144.7 (human) ng/gm wet weight. the three prostaglandins occurred in approximately equal amounts. Guinea=pig epidermal homogenates converted labeled arachidonic acid to PGE2 and PGF2alpha, the rate of formaiton being 10 and 2.5 pmoles per mg protein in O.K hr, respectively. Conversion in the dermis occurred to a much smaller extent. Homogenates of univolved and involved epidermis from 10 subjects with psoriasis produced PGE2 from arachidonic acid at rates of 6.48 and 2...", "contents": "Epidermal synthesis of prostaglandins and their effect on levels of cyclic adenosine 3', 5'monophosphate. Extracts of guinea-pig and human skin epidermis were analyzed for prostaglandins PGE1, E2, and F2alpha by radioimmunoassy, and found to contain a total of 62.0 (guinea pig) and 144.7 (human) ng/gm wet weight. the three prostaglandins occurred in approximately equal amounts. Guinea=pig epidermal homogenates converted labeled arachidonic acid to PGE2 and PGF2alpha, the rate of formaiton being 10 and 2.5 pmoles per mg protein in O.K hr, respectively. Conversion in the dermis occurred to a much smaller extent. Homogenates of univolved and involved epidermis from 10 subjects with psoriasis produced PGE2 from arachidonic acid at rates of 6.48 and 2..."} {"id": "PMID:167079", "title": "An in vitro and in vivo investigation of the phototoxic effect and its amelioration with radioprotective compounds.", "content": "Electron spin resonance spectroscopy has been used to demonstrate that the phototoxic antimalarial drug, 6,8-dichloro-2-phenyl-a-2-piperidnylquinolinemethanol (WR 7930), when irradiated with long-wave ultraviolet (UV) light (lambda greater than 320 nm) while held in a glassy matrix at 73 degrees K, enters a triplet state and releases hydrogen atoms in its environment. The steady-state concentration of triplet WR 7930 molecules and of hydrogen atoms is reduced 2 to 3 times when mercaptoethylamine (MEA) is also present in the UV-irradiated glass. Organosulfur radicals form on MEA while hydrogen atoms and triplet-state molecules are reduced in number. Hydrogen atoms and triplet WR 7930 molecules are considered as mediators of the phototoxicity of the antimalarial drug. Thus, hydrogen atom scavanging and chemical quenching of the triplet state are possible mechanisms by which protection against phototoxic effects could be gained. Protection is demonstrated in mice receiving 20 mg per kg WR 7930 intraperitoneally and exposed to long-wave UV for 20 hr when the radioprotective aminothiol-forming compound, 2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate (WR 2721), is administered at 400 mg per kg immediately before irradiation. When no protective drug is administered concurrently, WR 7930 administration results in intense erythema, edema, and eventual necrosis of ear tissues.", "contents": "An in vitro and in vivo investigation of the phototoxic effect and its amelioration with radioprotective compounds. Electron spin resonance spectroscopy has been used to demonstrate that the phototoxic antimalarial drug, 6,8-dichloro-2-phenyl-a-2-piperidnylquinolinemethanol (WR 7930), when irradiated with long-wave ultraviolet (UV) light (lambda greater than 320 nm) while held in a glassy matrix at 73 degrees K, enters a triplet state and releases hydrogen atoms in its environment. The steady-state concentration of triplet WR 7930 molecules and of hydrogen atoms is reduced 2 to 3 times when mercaptoethylamine (MEA) is also present in the UV-irradiated glass. Organosulfur radicals form on MEA while hydrogen atoms and triplet-state molecules are reduced in number. Hydrogen atoms and triplet WR 7930 molecules are considered as mediators of the phototoxicity of the antimalarial drug. Thus, hydrogen atom scavanging and chemical quenching of the triplet state are possible mechanisms by which protection against phototoxic effects could be gained. Protection is demonstrated in mice receiving 20 mg per kg WR 7930 intraperitoneally and exposed to long-wave UV for 20 hr when the radioprotective aminothiol-forming compound, 2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate (WR 2721), is administered at 400 mg per kg immediately before irradiation. When no protective drug is administered concurrently, WR 7930 administration results in intense erythema, edema, and eventual necrosis of ear tissues."} {"id": "PMID:167085", "title": "Non-chromaffin paraganglioma of the nasopharynx.", "content": "A case of non-chromaffin paraganglioma of the nasopharynx is presented. Previously reported cases are discussed and classified, and theories of origin are reviewed in the light of new evidence suggesting a common origin for this rare tumour and juvenile angiofibroma of the nasopharynx.", "contents": "Non-chromaffin paraganglioma of the nasopharynx. A case of non-chromaffin paraganglioma of the nasopharynx is presented. Previously reported cases are discussed and classified, and theories of origin are reviewed in the light of new evidence suggesting a common origin for this rare tumour and juvenile angiofibroma of the nasopharynx."} {"id": "PMID:167086", "title": "Effects of glucagon and dibutyryl adenosine 3', 5'-cyclic monophosphate on oxidative desaturation of fatty acids in the rat.", "content": "The present work was undertaken to study the effect of anti-insulinic and glycogenolytic factors on the oxidative desaturation of fatty acids. The effects of glucagon and dibutyryl cyclic AMP on the desaturation of linoleic acid to gamma-linolenic acid, alpha-linolenic acid to octadeca-6,9,12,15-tetraenoic acid, stearic acid to oleic acid, and eicosa-8,11,14-trienoic acid to eicosa-5,8,11,14-tetraenoic acid by rat liver microsomal preparations were investigated. Fasted rats had low desaturating activity, but refeeding a fat-free diet enhanced the activity. Administration of glucagon or dibutyryl cyclic AMP abolished the increase of the 6-desaturase activity elicited by refeeding. However, a similar effect on the 9-desaturase and 5-desaturase activity was not observed. The relationship between these effects and glucose metabolism is discussed.", "contents": "Effects of glucagon and dibutyryl adenosine 3', 5'-cyclic monophosphate on oxidative desaturation of fatty acids in the rat. The present work was undertaken to study the effect of anti-insulinic and glycogenolytic factors on the oxidative desaturation of fatty acids. The effects of glucagon and dibutyryl cyclic AMP on the desaturation of linoleic acid to gamma-linolenic acid, alpha-linolenic acid to octadeca-6,9,12,15-tetraenoic acid, stearic acid to oleic acid, and eicosa-8,11,14-trienoic acid to eicosa-5,8,11,14-tetraenoic acid by rat liver microsomal preparations were investigated. Fasted rats had low desaturating activity, but refeeding a fat-free diet enhanced the activity. Administration of glucagon or dibutyryl cyclic AMP abolished the increase of the 6-desaturase activity elicited by refeeding. However, a similar effect on the 9-desaturase and 5-desaturase activity was not observed. The relationship between these effects and glucose metabolism is discussed."} {"id": "PMID:167087", "title": "Turnover and tissue distribution of 125-I-labeled low density lipoprotein in swine and dogs.", "content": "Swine plasma low density lipoprotein (LDL) isolated ultracentrifugally (d 1.019-1.063) was labeled with 125-I, dialyzed, and reisolated by centrifugation at d 1.063. Over 96% of the radioactivity was shown to be associated with the apoprotein. After reinjection into the donor animal, disapperance of 125-I was followed for up to 122 hr. At all time intervals examined, over 95% of the total plasma 125-I was recovered in LDL (D 1.006-1.063), i.e., there was apparently no transfer of radioactivity to high density or very low density lipoproteins. The disappearance curve was biexponential, with half-lives of 0.83 plus or minus 0.06 and 22.5 plus or minus 1.7 hr for the first and second phases, respectively (13 studies). The mean calculated fractional catabolic rate was 0.041 plus or minus 0.003 hr-minus 1. Similar results were obtained in three dogs using autologous LDL of density 1.020-1.050; fractional catabolic rates were 0.031, 0.031, and 0.029 hr-minus 1. Tissue distribution of 125-I was determined in swine killed at various time intervals after [125-I]LDL injection with corrections for radioactivity in trapped plasma. Of the tissues examined, the liver showed by far the highest concentration. Total hepatic radioactivity, expressed as a percentage of total plasma radioactivity, was rather constant and independent of the time of killing from 3 to 122 hr (15.8 plus or minus 1.9%). The total extravascular LDL pool calculated from analysis of the plasma disappearance curves was about 20-30% of the size of the plasma LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool and that it is infairly rapid equilibrium with the plasma pool. To what extent the liver is involved in irreversible degradation cannot be inferred from these findings.", "contents": "Turnover and tissue distribution of 125-I-labeled low density lipoprotein in swine and dogs. Swine plasma low density lipoprotein (LDL) isolated ultracentrifugally (d 1.019-1.063) was labeled with 125-I, dialyzed, and reisolated by centrifugation at d 1.063. Over 96% of the radioactivity was shown to be associated with the apoprotein. After reinjection into the donor animal, disapperance of 125-I was followed for up to 122 hr. At all time intervals examined, over 95% of the total plasma 125-I was recovered in LDL (D 1.006-1.063), i.e., there was apparently no transfer of radioactivity to high density or very low density lipoproteins. The disappearance curve was biexponential, with half-lives of 0.83 plus or minus 0.06 and 22.5 plus or minus 1.7 hr for the first and second phases, respectively (13 studies). The mean calculated fractional catabolic rate was 0.041 plus or minus 0.003 hr-minus 1. Similar results were obtained in three dogs using autologous LDL of density 1.020-1.050; fractional catabolic rates were 0.031, 0.031, and 0.029 hr-minus 1. Tissue distribution of 125-I was determined in swine killed at various time intervals after [125-I]LDL injection with corrections for radioactivity in trapped plasma. Of the tissues examined, the liver showed by far the highest concentration. Total hepatic radioactivity, expressed as a percentage of total plasma radioactivity, was rather constant and independent of the time of killing from 3 to 122 hr (15.8 plus or minus 1.9%). The total extravascular LDL pool calculated from analysis of the plasma disappearance curves was about 20-30% of the size of the plasma LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool. These data are consistent with the conclusion that the liver accounts for a very large fraction of the total extravascular LDL pool and that it is infairly rapid equilibrium with the plasma pool. To what extent the liver is involved in irreversible degradation cannot be inferred from these findings."} {"id": "PMID:167090", "title": "Influence of the pituitary gland on insulin secretion in the genetically obese (ob/ob) mouse.", "content": "The influence of the pituitary gland of lean and genetically obese (ob/ob) mice on insulin secretion from microdissected pancreatic islets of lean and ob/ob mice has been studied by perifusing the pituitaries of these animals in series with the isolated islets and measuring insulin secretion at 5-min intervals over a period of 60 min. It has been shown that the pituitary perifusate of both lean and obese mice stimulate insulin secretion from lean mouse islets but not from obese mouse islets. The maximum stimulation occurs in the first 10 min and with the lean mouse pituitaries returns to the basal level in about 20 min, whereas with the obese mouse pituitaries insulin secretion is about double that from the control islets even after 40 min. A concentration of pure porcine ACTH equivalent to about three times the amount released from the pituitary gland under the experimental conditions used, caused only a small stimulation of insulin release. Possible interpretations of these findings and further lines of investigation are discussed.", "contents": "Influence of the pituitary gland on insulin secretion in the genetically obese (ob/ob) mouse. The influence of the pituitary gland of lean and genetically obese (ob/ob) mice on insulin secretion from microdissected pancreatic islets of lean and ob/ob mice has been studied by perifusing the pituitaries of these animals in series with the isolated islets and measuring insulin secretion at 5-min intervals over a period of 60 min. It has been shown that the pituitary perifusate of both lean and obese mice stimulate insulin secretion from lean mouse islets but not from obese mouse islets. The maximum stimulation occurs in the first 10 min and with the lean mouse pituitaries returns to the basal level in about 20 min, whereas with the obese mouse pituitaries insulin secretion is about double that from the control islets even after 40 min. A concentration of pure porcine ACTH equivalent to about three times the amount released from the pituitary gland under the experimental conditions used, caused only a small stimulation of insulin release. Possible interpretations of these findings and further lines of investigation are discussed."} {"id": "PMID:167092", "title": "Concentrations of cyclic AMP in rabbit ovarian tissue during the preovulatory period and pseudopregnancy after induction of ovulation by administration of human chorionic gonadotrophin.", "content": "Concentrations of cyclic AMP were measured in rabbit ovaries at various times after injection of an ovulatory dose of human chorionic gonadotrophin (HCG). A biphasic increase in cyclic AMP concentration occurred during the preovulatory period, with peaks 30 min and 3-4 h after HCG injection. Concentrations of cyclic AMP had returned to those observed in ovaries of control oestrous animals before the onset of ovulation 10-12 h after administration of HCG, and remained low throughout the period of pseudopregnancy. Concentrations of cyclic AMP in the newly formed and developing corpora lutea were similar to the concentrations observed in the remainder of the tissue during this period. No significant increase in cyclic AMP concentration was observed 7-9 days after initiation of ovulation. Concentrations of ATP were also investigated during the preovulatory period. The dose-response relationship of HCG to cyclic AMP production in oestrous rabbit ovaries was investigated.", "contents": "Concentrations of cyclic AMP in rabbit ovarian tissue during the preovulatory period and pseudopregnancy after induction of ovulation by administration of human chorionic gonadotrophin. Concentrations of cyclic AMP were measured in rabbit ovaries at various times after injection of an ovulatory dose of human chorionic gonadotrophin (HCG). A biphasic increase in cyclic AMP concentration occurred during the preovulatory period, with peaks 30 min and 3-4 h after HCG injection. Concentrations of cyclic AMP had returned to those observed in ovaries of control oestrous animals before the onset of ovulation 10-12 h after administration of HCG, and remained low throughout the period of pseudopregnancy. Concentrations of cyclic AMP in the newly formed and developing corpora lutea were similar to the concentrations observed in the remainder of the tissue during this period. No significant increase in cyclic AMP concentration was observed 7-9 days after initiation of ovulation. Concentrations of ATP were also investigated during the preovulatory period. The dose-response relationship of HCG to cyclic AMP production in oestrous rabbit ovaries was investigated."} {"id": "PMID:167093", "title": "The pituitary-adrenal system of the genetically obese (ob/ob) mouse.", "content": "Adult genetically obese (ob/ob) mice which are characterized by adrenal hypertrophy and increased secretion of corticosteroids have considerably increased levels of ACTH in the pituitary gland. At 5 weeks of age there is no difference in the pituitary ACTH content of lean and obese animals and dietary restriction, sufficient to maintain body weight at normal values, reduces the pituitary ACTH content of adult obese mice from 14 times the level found in lean litter-mate controls to almost normal values. Using an in-vitro perifusion system, the release of ACTH from isolated pituitary glands was studied. Pituitaries from lean and obese mice responded similarly to stimulation with a crude extract of hypothalamic tissue containing coticotrophin releasing factor (CRF). The CRF content of the hypothalamus in both groups appears to be similar. In contrast with the high pituitary content, plasma values for ACTH in unstressed obese mice are not increased. The results are discussed in relation to other evidence for a hypothalamic disorder in ob/ob mice.", "contents": "The pituitary-adrenal system of the genetically obese (ob/ob) mouse. Adult genetically obese (ob/ob) mice which are characterized by adrenal hypertrophy and increased secretion of corticosteroids have considerably increased levels of ACTH in the pituitary gland. At 5 weeks of age there is no difference in the pituitary ACTH content of lean and obese animals and dietary restriction, sufficient to maintain body weight at normal values, reduces the pituitary ACTH content of adult obese mice from 14 times the level found in lean litter-mate controls to almost normal values. Using an in-vitro perifusion system, the release of ACTH from isolated pituitary glands was studied. Pituitaries from lean and obese mice responded similarly to stimulation with a crude extract of hypothalamic tissue containing coticotrophin releasing factor (CRF). The CRF content of the hypothalamus in both groups appears to be similar. In contrast with the high pituitary content, plasma values for ACTH in unstressed obese mice are not increased. The results are discussed in relation to other evidence for a hypothalamic disorder in ob/ob mice."} {"id": "PMID:167094", "title": "In vitro studies on allotype suppression. III. compounds of antiallyotype serum active in release from allotype suppression.", "content": "Spleen cells of b4b6 rabbits, shown to be deficient in their ability to produce b4Ig due to prenatal exposure to anti-b4, formed anti-T2 antibodies marked with the b4 determinant in response to solubilized T2 phage (S-T2) only when cultured in the presence of antibodies specific for the nonsuppressed type (b6), thus confirming and extending the previously reported observation of release from b4 suppression in cultured cells of b4-suppressed b4b5 rabbits treated with anti-b5 serum. Only antiallotype sera made in b4 rabbits were active in reversing b4 suppression. Anti-b5 or anti-b6 sera from rabbits of allotypes b6 or b5, respectively, when used in concentrations which completely or partially inhibited the formation of anti-T2 antibodies marked with the corresponding nonsuppressed allotype of the spleen donor, proved to be almost completely ineffective in causing release of suppression. Exceptions were noted when spleen cells of rabbits advanced in spontaneous escape from suppression were tested with such sera. The addition of normal b4 serum to non-b4 antiallotypic sera rendered them as effective in releasing b4 suppression in vitro as were antisera from b4 rabbits. Furthermore, the capacity of a b4 antiallotype serum to cause reversal of b4 suppression could be potentiated by the addition of normal b4 serum, indicating that nonantibody b4 Ig is a limiting factor in such a serum. Thus, the release from allotype suppression observed in cultures of spleen cells from b4-suppressed heterozygous rabbits is dependent upon the presence of two components: antibodies directed against the nonsuppressed allotype of the donor and normal b4Ig. These findings are interpreted in terms of alternate hypotheses involving (a) a mechanism of b4 derepression and (b) inactivation of a suppressor cell with recognition for a b4-labeled target.", "contents": "In vitro studies on allotype suppression. III. compounds of antiallyotype serum active in release from allotype suppression. Spleen cells of b4b6 rabbits, shown to be deficient in their ability to produce b4Ig due to prenatal exposure to anti-b4, formed anti-T2 antibodies marked with the b4 determinant in response to solubilized T2 phage (S-T2) only when cultured in the presence of antibodies specific for the nonsuppressed type (b6), thus confirming and extending the previously reported observation of release from b4 suppression in cultured cells of b4-suppressed b4b5 rabbits treated with anti-b5 serum. Only antiallotype sera made in b4 rabbits were active in reversing b4 suppression. Anti-b5 or anti-b6 sera from rabbits of allotypes b6 or b5, respectively, when used in concentrations which completely or partially inhibited the formation of anti-T2 antibodies marked with the corresponding nonsuppressed allotype of the spleen donor, proved to be almost completely ineffective in causing release of suppression. Exceptions were noted when spleen cells of rabbits advanced in spontaneous escape from suppression were tested with such sera. The addition of normal b4 serum to non-b4 antiallotypic sera rendered them as effective in releasing b4 suppression in vitro as were antisera from b4 rabbits. Furthermore, the capacity of a b4 antiallotype serum to cause reversal of b4 suppression could be potentiated by the addition of normal b4 serum, indicating that nonantibody b4 Ig is a limiting factor in such a serum. Thus, the release from allotype suppression observed in cultures of spleen cells from b4-suppressed heterozygous rabbits is dependent upon the presence of two components: antibodies directed against the nonsuppressed allotype of the donor and normal b4Ig. These findings are interpreted in terms of alternate hypotheses involving (a) a mechanism of b4 derepression and (b) inactivation of a suppressor cell with recognition for a b4-labeled target."} {"id": "PMID:167095", "title": "Secretion of a specific collagenase by stimulated macrophages.", "content": "Thioglycollate-stimulated mouse macrophages release a specific collagenase into their medium during in vitro culture. The macrophage collagenase has been characterized as a typical metal proteinase which catalyzes the cleavage of the native collagen molecule into three and one-quarter fragments. The extracellular accumulation and low activity in cell lysates suggest that collagenase is a secretion product of the stimulated macrophage. Prolonged secretion of the enzyme at a constant rate for more than 7 days in culture and its inhibition by cycloheximide provide evidence for biosynthesis in vitro. In contrast, secretion of collagenase is barely detectable from unstimulated macrophages which can, however, be stimulated to secret the enzyme by ingestion and intralysosomal storage of latex particles or dextran sulfate. Macrophages laden with latex, an undigestable particle, continue to release collagenase for at least 20 days. Several established mouse cell lines have also been examined for their capacity to secrete collagenase. Collagenase is one of a class of inducible neutral proteinases by which the activated macrophage can modify its extracellular environment.", "contents": "Secretion of a specific collagenase by stimulated macrophages. Thioglycollate-stimulated mouse macrophages release a specific collagenase into their medium during in vitro culture. The macrophage collagenase has been characterized as a typical metal proteinase which catalyzes the cleavage of the native collagen molecule into three and one-quarter fragments. The extracellular accumulation and low activity in cell lysates suggest that collagenase is a secretion product of the stimulated macrophage. Prolonged secretion of the enzyme at a constant rate for more than 7 days in culture and its inhibition by cycloheximide provide evidence for biosynthesis in vitro. In contrast, secretion of collagenase is barely detectable from unstimulated macrophages which can, however, be stimulated to secret the enzyme by ingestion and intralysosomal storage of latex particles or dextran sulfate. Macrophages laden with latex, an undigestable particle, continue to release collagenase for at least 20 days. Several established mouse cell lines have also been examined for their capacity to secrete collagenase. Collagenase is one of a class of inducible neutral proteinases by which the activated macrophage can modify its extracellular environment."} {"id": "PMID:167096", "title": "Elastase secretion by stimulated macrophages. Characterization and regulation.", "content": "Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.", "contents": "Elastase secretion by stimulated macrophages. Characterization and regulation. Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema."} {"id": "PMID:167097", "title": "New mutant and congenic mouse stocks expressing the murine leukemia virus-associated thymocyte surface antigen GIX.", "content": "For several reasons the G(IX) antigen (1) has a prominent place in current work on murine leukemia virus (MuLV): In the prototype G(IX+) mouse strain 129, the G(IX) trait is mendelian, and is expressed selectively (though not exclusively) on thymocytes. Thus, expression of this cell surface component is under the control of cellular genes and is subject to the controls governing the differentiation of T lymphocytes (2). Although the 129 mouse produces no demonstrable leukemia virus such as that found in the AKR strain, it was soon realized that G(IX) antigen must in some way be related to MuLV, because productive infection with MuLV is frequently associated with appearance of G(IX) antigen on cells that are genotypically G(IX-), most notably on MuLV-infected rat cells, or cells that belong to other differentiation pathways (1). The basis of this connection between G(IX) and MuLV has recently become clear from the demonstration that G(IX) is one of MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) is one of the antigens present on gp69/71 (3,4), the major glycoprotein component of the MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) antigen always denotes the presence of gp69/71 (though not all variants of gp69/71 need necessarily carry G(IX)). Study of the circumstances under which G(IX) is expressed on the cell surface is thus potentially a powerful approach to understanding how the expression of C-type viral genomes is controlled. Such studies are greatly facilitated by the availability of mutant and congenic strains of inbred mice which differ from the nonmutant or partner strains only with respect to one or another manifestation of the viral genome. It is for this reason that we record here (Table I) some details of two G(IX) mutant and two G(IX) congenic stocks derived in our colonies at Memorial Sloan-Kettering Cancer Center (MSKCC). In addition, to these four strains, Table I includes data for the three relevant partner strains, and for strain AKR, for comparison. These eight strains all differ from one another with respect to one or more MuLV-related traits.", "contents": "New mutant and congenic mouse stocks expressing the murine leukemia virus-associated thymocyte surface antigen GIX. For several reasons the G(IX) antigen (1) has a prominent place in current work on murine leukemia virus (MuLV): In the prototype G(IX+) mouse strain 129, the G(IX) trait is mendelian, and is expressed selectively (though not exclusively) on thymocytes. Thus, expression of this cell surface component is under the control of cellular genes and is subject to the controls governing the differentiation of T lymphocytes (2). Although the 129 mouse produces no demonstrable leukemia virus such as that found in the AKR strain, it was soon realized that G(IX) antigen must in some way be related to MuLV, because productive infection with MuLV is frequently associated with appearance of G(IX) antigen on cells that are genotypically G(IX-), most notably on MuLV-infected rat cells, or cells that belong to other differentiation pathways (1). The basis of this connection between G(IX) and MuLV has recently become clear from the demonstration that G(IX) is one of MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) is one of the antigens present on gp69/71 (3,4), the major glycoprotein component of the MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) antigen always denotes the presence of gp69/71 (though not all variants of gp69/71 need necessarily carry G(IX)). Study of the circumstances under which G(IX) is expressed on the cell surface is thus potentially a powerful approach to understanding how the expression of C-type viral genomes is controlled. Such studies are greatly facilitated by the availability of mutant and congenic strains of inbred mice which differ from the nonmutant or partner strains only with respect to one or another manifestation of the viral genome. It is for this reason that we record here (Table I) some details of two G(IX) mutant and two G(IX) congenic stocks derived in our colonies at Memorial Sloan-Kettering Cancer Center (MSKCC). In addition, to these four strains, Table I includes data for the three relevant partner strains, and for strain AKR, for comparison. These eight strains all differ from one another with respect to one or more MuLV-related traits."} {"id": "PMID:167098", "title": "Expression of murine leukemia virus envelope glycoprotein gp69/71 on mouse thymocytes. Evidence for two structural variants distinguished by presence vs. absence of GIX antigen.", "content": "Thymocytes of several mouse strains were tested for expression of the gp69/71 envelope component of murine leukemia virus by surface iodination, followed by immunoprecipitation and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Theses strains included two congenic lines differing from their partner stocks with respect to expression of GIX antigen demonstrable in the cytoxicity assay. We conclude that:(a) two structural variants of gp69/71 can be expressed on mouse thymocytes, (b) these are distinguishable by a small difference in mobility in SDS gels, (c) one carries GIX antigen and the other not, (d) they are coded, or their expression is regulated, by different chromosomal loci that are not closely linked, and (e) both can be expressed together on the thymocytes of inbred mice. In the intact thymocyte plasma membrane, the sites of group-specific antigen shared by the two gp69/71 variants, unlike the GIX type specificity carried by only one of them, are probably inaccessible to antibody.", "contents": "Expression of murine leukemia virus envelope glycoprotein gp69/71 on mouse thymocytes. Evidence for two structural variants distinguished by presence vs. absence of GIX antigen. Thymocytes of several mouse strains were tested for expression of the gp69/71 envelope component of murine leukemia virus by surface iodination, followed by immunoprecipitation and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Theses strains included two congenic lines differing from their partner stocks with respect to expression of GIX antigen demonstrable in the cytoxicity assay. We conclude that:(a) two structural variants of gp69/71 can be expressed on mouse thymocytes, (b) these are distinguishable by a small difference in mobility in SDS gels, (c) one carries GIX antigen and the other not, (d) they are coded, or their expression is regulated, by different chromosomal loci that are not closely linked, and (e) both can be expressed together on the thymocytes of inbred mice. In the intact thymocyte plasma membrane, the sites of group-specific antigen shared by the two gp69/71 variants, unlike the GIX type specificity carried by only one of them, are probably inaccessible to antibody."} {"id": "PMID:167099", "title": "Fibroblast surface antigen produced but not retained by virus-transformed human cells.", "content": "Normal human fibroblasts contain a cell type-specific glycoprotein antigen (SF) that is known to be slowly shed into the medium and to be present also in human serum. Immunofluorescence with anti-SF antibodies showed that SF antigen has a highly nonrandom fibrillar distribution in surface of normal fibroblasts. Simian virus 40-transformed fibroblasts also produced the SF antigen, as shown by radioimmunoassay or immunodiffusion tests, but it was not retained by the surface of these cells. This creates a major difference between the surfaces of normal and malignant cells.", "contents": "Fibroblast surface antigen produced but not retained by virus-transformed human cells. Normal human fibroblasts contain a cell type-specific glycoprotein antigen (SF) that is known to be slowly shed into the medium and to be present also in human serum. Immunofluorescence with anti-SF antibodies showed that SF antigen has a highly nonrandom fibrillar distribution in surface of normal fibroblasts. Simian virus 40-transformed fibroblasts also produced the SF antigen, as shown by radioimmunoassay or immunodiffusion tests, but it was not retained by the surface of these cells. This creates a major difference between the surfaces of normal and malignant cells."} {"id": "PMID:167102", "title": "The identification and purification of multiple forms of theta-haemolysin (theta-toxin) of Clostridium perfringens type A.", "content": "The theta-haemolysin of Clostridium perfringens was purified from culture supernatant fluids of type A strains by fractional ammonium sulphate precipitation and isoelectric focusing in narrow pH 5 to 8 gradients. Four components detected on electrofocusing were designated theta-1(pI6-8to6-9),theta-2(pI6-5to6-6),theta-3(pI6-1to6-3) and theta-4(pI5-7to5-9). Specific activities ranged from 0-4 x 10-6 to 1-2 x 10-6 haemolytic units/mg protein and 2950 to 3600 LD-50/mg protein. Each haemolytic component was activated by cysteine hydrochloride, and inactivated by cholesterol, by addition of sheep erythrocyte ghosts and by heating at 60 degrees C for 10 min; mouse erythrocytes were more resistant than sheep erythrocytes to haemolysis. A reaction of identity was obtained between components in gel diffusion. Sodium dodecyl sulphate polyacrylamide discgel electrophoresis gave molecular weights in the range 59,000 to 62,000 for each component. A similar value was obtained for theta-1 on density gradient ultracentrifugation. Although the multiple forms were free of 11 factors present in culture supernatants, crossed immunoelectrophoresis and disc gel electrophoresis revealed minor contaminants. These studies reveal that theta-haemolysin has physical properties in common with other oxygen-labile haemolysins.", "contents": "The identification and purification of multiple forms of theta-haemolysin (theta-toxin) of Clostridium perfringens type A. The theta-haemolysin of Clostridium perfringens was purified from culture supernatant fluids of type A strains by fractional ammonium sulphate precipitation and isoelectric focusing in narrow pH 5 to 8 gradients. Four components detected on electrofocusing were designated theta-1(pI6-8to6-9),theta-2(pI6-5to6-6),theta-3(pI6-1to6-3) and theta-4(pI5-7to5-9). Specific activities ranged from 0-4 x 10-6 to 1-2 x 10-6 haemolytic units/mg protein and 2950 to 3600 LD-50/mg protein. Each haemolytic component was activated by cysteine hydrochloride, and inactivated by cholesterol, by addition of sheep erythrocyte ghosts and by heating at 60 degrees C for 10 min; mouse erythrocytes were more resistant than sheep erythrocytes to haemolysis. A reaction of identity was obtained between components in gel diffusion. Sodium dodecyl sulphate polyacrylamide discgel electrophoresis gave molecular weights in the range 59,000 to 62,000 for each component. A similar value was obtained for theta-1 on density gradient ultracentrifugation. Although the multiple forms were free of 11 factors present in culture supernatants, crossed immunoelectrophoresis and disc gel electrophoresis revealed minor contaminants. These studies reveal that theta-haemolysin has physical properties in common with other oxygen-labile haemolysins."} {"id": "PMID:167103", "title": "Nature of the determinant responsible for the adhesion of lactobacilli to chicken crop epithelial cells.", "content": "Using an in vitro method, some factors affecting the attachment of a strain of lactobacillus to chicken crop epithelial cells have been studied. Time of contact beyond 10 min, pH value, age or growth temperature of the bacterial culture, or nature of the energy source in the growth medium had little or no effect on attachment. Heating to 100 degrees C for 10 min, or treatment with EDTA or surface active compounds was also without effect. Treatment with sodium periodate markedly decreased adhesion, proteolytic enzymes had a smaller effect but wheat germ lipase was completely inactive. The pronounced inhibition of adhesion by periodate suggested the invovement of carbohydrate. However, enzymes known to attack carbohydrate substrates were inactive in reducing adhesion. Concanavalin A, which binds specifically to certain sugar residues, reduced attachment. It is suggested that these concanavalin A receptors on the lactobacillus are responsible for its attachment to crop epithelial cells.", "contents": "Nature of the determinant responsible for the adhesion of lactobacilli to chicken crop epithelial cells. Using an in vitro method, some factors affecting the attachment of a strain of lactobacillus to chicken crop epithelial cells have been studied. Time of contact beyond 10 min, pH value, age or growth temperature of the bacterial culture, or nature of the energy source in the growth medium had little or no effect on attachment. Heating to 100 degrees C for 10 min, or treatment with EDTA or surface active compounds was also without effect. Treatment with sodium periodate markedly decreased adhesion, proteolytic enzymes had a smaller effect but wheat germ lipase was completely inactive. The pronounced inhibition of adhesion by periodate suggested the invovement of carbohydrate. However, enzymes known to attack carbohydrate substrates were inactive in reducing adhesion. Concanavalin A, which binds specifically to certain sugar residues, reduced attachment. It is suggested that these concanavalin A receptors on the lactobacillus are responsible for its attachment to crop epithelial cells."} {"id": "PMID:167104", "title": "Chemical mutagenesis of Fusarium oxysporum f. sp. lycopersici: non-selected changes in pathogenicity of auxotrophic mutants.", "content": "Single and multiple auxotrophic mutants of the Fusarium oxysporum f. sp.lycopersici strains which cause Fusarium crown-rot and Fusarium wilt of tomato were obtained by chemical mutagenesis with nitrous acid, nitrosoguandidine and ethylmethaneulphonate. The mutagenesis and selection procedures, adapted for use with a plant pathogenic fungus, are described. Changes in pathogenicity were observed when the auxotrophs were compared with the wild type but no correlation was observed between changes in pathogenicity and the particular nutritional requirement.", "contents": "Chemical mutagenesis of Fusarium oxysporum f. sp. lycopersici: non-selected changes in pathogenicity of auxotrophic mutants. Single and multiple auxotrophic mutants of the Fusarium oxysporum f. sp.lycopersici strains which cause Fusarium crown-rot and Fusarium wilt of tomato were obtained by chemical mutagenesis with nitrous acid, nitrosoguandidine and ethylmethaneulphonate. The mutagenesis and selection procedures, adapted for use with a plant pathogenic fungus, are described. Changes in pathogenicity were observed when the auxotrophs were compared with the wild type but no correlation was observed between changes in pathogenicity and the particular nutritional requirement."} {"id": "PMID:167105", "title": "Fate of parental simian virus 40 DNA in permissive monkey kidney cells.", "content": "The fate of parental SV40 DNA in monkey kidney cells was investigated by infecting the cells with purified virus labelled with [3-H]-thymidine. 5-Bromodeoxyuridine (200 mug/ml) was added to the cells at 2 h after infection to label virus progeny DNA. At 72 h post-infection the cells were harvested and virus DNA was extracted and fractionated by isopycnic sedimentation in CsCL solution. The following DNAs with characteristic densities were found: light (LL), 1.70 g/ml; hybrid (HL), 1-75 g/ml and heavy DNA (HH), 1-80 g/ml. Of the total cell-associated [3-H]-radioactivity (derived from parental virus), more than 90% was recovered in unreplicated parental DNA(LL DNA), about 2% was recovered in the HL DNA and about 1-7% was associated with the HH DNA. The unreplicated parental DNA was present as uncoated intact DNA complexed with proteins present in the infected cell. The HL DNA contains one light parental and one heavy progeny DNA strand. The nature of the radioactivity present in the HH DNA remains to be determined.", "contents": "Fate of parental simian virus 40 DNA in permissive monkey kidney cells. The fate of parental SV40 DNA in monkey kidney cells was investigated by infecting the cells with purified virus labelled with [3-H]-thymidine. 5-Bromodeoxyuridine (200 mug/ml) was added to the cells at 2 h after infection to label virus progeny DNA. At 72 h post-infection the cells were harvested and virus DNA was extracted and fractionated by isopycnic sedimentation in CsCL solution. The following DNAs with characteristic densities were found: light (LL), 1.70 g/ml; hybrid (HL), 1-75 g/ml and heavy DNA (HH), 1-80 g/ml. Of the total cell-associated [3-H]-radioactivity (derived from parental virus), more than 90% was recovered in unreplicated parental DNA(LL DNA), about 2% was recovered in the HL DNA and about 1-7% was associated with the HH DNA. The unreplicated parental DNA was present as uncoated intact DNA complexed with proteins present in the infected cell. The HL DNA contains one light parental and one heavy progeny DNA strand. The nature of the radioactivity present in the HH DNA remains to be determined."} {"id": "PMID:167106", "title": "Polyamine metabolism in cells infected with herpes simplex virus.", "content": "Ifection of LS cells with HSV-1 resulted in an inhibition of spermidine and spermine synthesis from putrescine, possibly through inhibition of host cell protein synthesis. The rate of putrescine uptake increased soon after infection, and later, polyamines were lost from the cells. Inhibition of spermidine and spermine synthesis by methylglyoxal bis (amidinohydrazone) did not affect virus replication.", "contents": "Polyamine metabolism in cells infected with herpes simplex virus. Ifection of LS cells with HSV-1 resulted in an inhibition of spermidine and spermine synthesis from putrescine, possibly through inhibition of host cell protein synthesis. The rate of putrescine uptake increased soon after infection, and later, polyamines were lost from the cells. Inhibition of spermidine and spermine synthesis by methylglyoxal bis (amidinohydrazone) did not affect virus replication."} {"id": "PMID:167107", "title": "Are cytotoxicity and interferon inducing activity of poly(I).poly(C) invariably linked in interferon-treated L cells.", "content": "Interferon-treated L cells exhibit a specific enhanced susceptibility to the cytotoxic and interferon inducing activities of double-stranded RNAs such as poly(1). poly(C). These activities remained closely linked through widely varying assay conditions, involving, for example, different time anddosage schedules of poly(1). poly (C),suggesting that there is at least one common step in the mechanisms leading to interferon formation and toxicity in interferon-primed cells exposed to poly(1).poly(C). However, some procedures such as addition of metabolic inhibitors (actinomycin D, cycloheximide) and repeated administration of poly(1).poly(C) suppressed the interferon inducing capacity of poly(1).poly(C) without a concomitant decrease of toxicity. Other procedures such as brief treatment of the cells with interferon or DEAE-dextran permitted full expression of the interferon inducing activity of poly(1).poly(C) without any sign of toxicity. The latter results suggest that the mechanisms underlying interferon production and toxicity of poly(1).poly(C) in interferon-treated L cells diverge from a certain point onward.", "contents": "Are cytotoxicity and interferon inducing activity of poly(I).poly(C) invariably linked in interferon-treated L cells. Interferon-treated L cells exhibit a specific enhanced susceptibility to the cytotoxic and interferon inducing activities of double-stranded RNAs such as poly(1). poly(C). These activities remained closely linked through widely varying assay conditions, involving, for example, different time anddosage schedules of poly(1). poly (C),suggesting that there is at least one common step in the mechanisms leading to interferon formation and toxicity in interferon-primed cells exposed to poly(1).poly(C). However, some procedures such as addition of metabolic inhibitors (actinomycin D, cycloheximide) and repeated administration of poly(1).poly(C) suppressed the interferon inducing capacity of poly(1).poly(C) without a concomitant decrease of toxicity. Other procedures such as brief treatment of the cells with interferon or DEAE-dextran permitted full expression of the interferon inducing activity of poly(1).poly(C) without any sign of toxicity. The latter results suggest that the mechanisms underlying interferon production and toxicity of poly(1).poly(C) in interferon-treated L cells diverge from a certain point onward."} {"id": "PMID:167108", "title": "Ultrastructural aspects of BK virus uptake and replication in human fibroblasts.", "content": "After exposure of human embryonic fibroblasts to BK virus, virus particles adsorbed to the plasma membrane were engulfed by pinocytosis or captured by vesicles, possibly originating from the endoplasmic reticulum, within 2 h after infection. Most of the virus particles were then transported into lysosomes or into the nucleus, while a small amount of virus was found free in the cytoplasm. Virus particles entered the nucleus between 2 and 12 h after infection, were still detectable in the nucleus at 24 h after infectionand becamse morphologically undiscernible at 30 h after infection, suggesting that a nuclear uncoating mechanism was active between 24 and 30 h after infection. Virus progeny started to appear in the nucleus of infected cells at 4 days after infection, but not until 7 to 8 days after infection did the virus escape into the cytoplasm and cell degeneration became evident. The possible explanations for the long replicative cycle of BK virus are discussed.", "contents": "Ultrastructural aspects of BK virus uptake and replication in human fibroblasts. After exposure of human embryonic fibroblasts to BK virus, virus particles adsorbed to the plasma membrane were engulfed by pinocytosis or captured by vesicles, possibly originating from the endoplasmic reticulum, within 2 h after infection. Most of the virus particles were then transported into lysosomes or into the nucleus, while a small amount of virus was found free in the cytoplasm. Virus particles entered the nucleus between 2 and 12 h after infection, were still detectable in the nucleus at 24 h after infectionand becamse morphologically undiscernible at 30 h after infection, suggesting that a nuclear uncoating mechanism was active between 24 and 30 h after infection. Virus progeny started to appear in the nucleus of infected cells at 4 days after infection, but not until 7 to 8 days after infection did the virus escape into the cytoplasm and cell degeneration became evident. The possible explanations for the long replicative cycle of BK virus are discussed."} {"id": "PMID:167109", "title": "Iterferon induction in mice by BHK cells persistently infected with HVJ.", "content": "Intraperitoneal injection into mice of BHK-HVJ cells (BHK cells persistently infected with HVJ) induced considerable amounts of circulating interferon. Sonication of BHK-HVJ cells almost totally abolished their interferon inducing capacities. This result suggests that a certain native organized structure of virus infected cells might be essential for production of interferon in this system, as is suggested in the in vitro sytem.", "contents": "Iterferon induction in mice by BHK cells persistently infected with HVJ. Intraperitoneal injection into mice of BHK-HVJ cells (BHK cells persistently infected with HVJ) induced considerable amounts of circulating interferon. Sonication of BHK-HVJ cells almost totally abolished their interferon inducing capacities. This result suggests that a certain native organized structure of virus infected cells might be essential for production of interferon in this system, as is suggested in the in vitro sytem."} {"id": "PMID:167110", "title": "Transformation by a temperature sensitive mutant of Rous sarcoma virus in the absence of serum.", "content": "Cultures of chicken embryo fibroblasts infected with the temperature-sensitive transformation mutant of Rous sarcoma virus, tsLA24PR-A, were arrested between mitosis and S phase by exposure to serum-free medium at the non-permissive temperature (41degree C) for 2 days. On shifting to the permissive temperature (35degree C) the cells assumed a transformed morphology and increased uptake of [2minus 3H]-Deoxy-glucose. There was a concomitant increase in acid insoluble [3H]-thymidine. This suggests that the virus transforming function can cause stationary cells to enter their growth cycle. The level of release of infectious virus was shown to decrease on cell cycle arrest in serum-free medium and not to recover on a shift to 35 degrees, when cellular DNA synthesis and transformation was induced. Cultures rendered stationary in medium containing serum depleted of multiplication stimulating factor did not show this reduction in virus production.", "contents": "Transformation by a temperature sensitive mutant of Rous sarcoma virus in the absence of serum. Cultures of chicken embryo fibroblasts infected with the temperature-sensitive transformation mutant of Rous sarcoma virus, tsLA24PR-A, were arrested between mitosis and S phase by exposure to serum-free medium at the non-permissive temperature (41degree C) for 2 days. On shifting to the permissive temperature (35degree C) the cells assumed a transformed morphology and increased uptake of [2minus 3H]-Deoxy-glucose. There was a concomitant increase in acid insoluble [3H]-thymidine. This suggests that the virus transforming function can cause stationary cells to enter their growth cycle. The level of release of infectious virus was shown to decrease on cell cycle arrest in serum-free medium and not to recover on a shift to 35 degrees, when cellular DNA synthesis and transformation was induced. Cultures rendered stationary in medium containing serum depleted of multiplication stimulating factor did not show this reduction in virus production."} {"id": "PMID:167111", "title": "Evidence for a host cell surface antigen on the envelope of avian tumour viruses.", "content": "Avian sarcoma viruses of the A, B, C, D and E subgroups are inactivated about 100-fold by the serum of rabbits immunized against chick embryo (CE) cells, in the presence, but not in the absence, of complement. The inactivation is not due to the action of the antiserum and complement on the CE cell cultures used for virus assay, nor to anti-Forssman antibodies, but it is presumably due to antibodies to some antigen(s) common to the surface of CE cells and to the virus envelope. This host cell surface antigen (HSCA) is also present on the surface of the helper viruses RAV1 and RAV2 of Bryan strain Rous sacroma virus. However, it cannot be said whether it is identical for viruses of all subgroups. A parallel electron microscopical study has revealed a characteristic swelling and loss of opacity to electrons of virus particles treated with the antiserum and complement, which appears to precede virolysis. Avian sarcoma viruses are not inactivated, in the presence or absence of complement, by antiserum to BHK21 hamster cells transformed by RSV and carrying virus-induced surface antigen (VISA). Therefore, the virus particles do not carry any surface antigen common to transformed non-permissive and permissive cells.", "contents": "Evidence for a host cell surface antigen on the envelope of avian tumour viruses. Avian sarcoma viruses of the A, B, C, D and E subgroups are inactivated about 100-fold by the serum of rabbits immunized against chick embryo (CE) cells, in the presence, but not in the absence, of complement. The inactivation is not due to the action of the antiserum and complement on the CE cell cultures used for virus assay, nor to anti-Forssman antibodies, but it is presumably due to antibodies to some antigen(s) common to the surface of CE cells and to the virus envelope. This host cell surface antigen (HSCA) is also present on the surface of the helper viruses RAV1 and RAV2 of Bryan strain Rous sacroma virus. However, it cannot be said whether it is identical for viruses of all subgroups. A parallel electron microscopical study has revealed a characteristic swelling and loss of opacity to electrons of virus particles treated with the antiserum and complement, which appears to precede virolysis. Avian sarcoma viruses are not inactivated, in the presence or absence of complement, by antiserum to BHK21 hamster cells transformed by RSV and carrying virus-induced surface antigen (VISA). Therefore, the virus particles do not carry any surface antigen common to transformed non-permissive and permissive cells."} {"id": "PMID:167112", "title": "Genetic control of resistance of chick embryo cultures to RSV (RAV 50).", "content": "The genetic control of resistance of chick embryo cultures to RSV (RAV 50) was studied in crosses between the highly inbred Reaseheath lines, I, C and W and in the test-cross between WC(F1) and RPRL line 7. Embryo cultures resistant to RSV(RAV2) were also resistant to RSV(RAV 50). Genetic analysis of the segregation results of resistance and susceptibility in the F2, back-crosses, and test-cross populations suggests that the tvb genes pleiotropically control the resistance of the embryo cultures to RSV(RAV 50).", "contents": "Genetic control of resistance of chick embryo cultures to RSV (RAV 50). The genetic control of resistance of chick embryo cultures to RSV (RAV 50) was studied in crosses between the highly inbred Reaseheath lines, I, C and W and in the test-cross between WC(F1) and RPRL line 7. Embryo cultures resistant to RSV(RAV2) were also resistant to RSV(RAV 50). Genetic analysis of the segregation results of resistance and susceptibility in the F2, back-crosses, and test-cross populations suggests that the tvb genes pleiotropically control the resistance of the embryo cultures to RSV(RAV 50)."} {"id": "PMID:167113", "title": "Location and abundance of poly (A) sequences in Sendai virus messenger RNA molecules.", "content": "Adenine-rich sequences from 18S Sendai virus messenger RNA species were 99% adenylate, 3'-OH terminal, and were present in at least 50% of the RNA molecules. Intact virus messenger RNA molecules were resistant to exonucleolytic attack by polynucleotide phosphorylase, suggesting that their 3'-termini are masked.", "contents": "Location and abundance of poly (A) sequences in Sendai virus messenger RNA molecules. Adenine-rich sequences from 18S Sendai virus messenger RNA species were 99% adenylate, 3'-OH terminal, and were present in at least 50% of the RNA molecules. Intact virus messenger RNA molecules were resistant to exonucleolytic attack by polynucleotide phosphorylase, suggesting that their 3'-termini are masked."} {"id": "PMID:167114", "title": "Replication of reticuloendotheliosis viruses in cell culture: chronic infection.", "content": "After an initial acute infection with cell killing, chicken or duck embryo fibroblasts infected in culture with reticuloendotheliosis viruses set up a chronic infection with no cell killing or morphological transformation. Essentially all of the chronically infected cells produced virus. The virus production was not sensitive to cytosine arabinoside or mitomycin C as was virus production in an acute infection. The chronically infected cells had a strong group-specific resistancto the c.p.e. of superinfecting reticuloendotheliosis viruses. However, they were sensitive to vesicular stomatitis virus and avian leukosis-sarcoma viruses. After double infection, single cells produced reticuloendotheliosis virus and avian leukosis-sarcoma virus.", "contents": "Replication of reticuloendotheliosis viruses in cell culture: chronic infection. After an initial acute infection with cell killing, chicken or duck embryo fibroblasts infected in culture with reticuloendotheliosis viruses set up a chronic infection with no cell killing or morphological transformation. Essentially all of the chronically infected cells produced virus. The virus production was not sensitive to cytosine arabinoside or mitomycin C as was virus production in an acute infection. The chronically infected cells had a strong group-specific resistancto the c.p.e. of superinfecting reticuloendotheliosis viruses. However, they were sensitive to vesicular stomatitis virus and avian leukosis-sarcoma viruses. After double infection, single cells produced reticuloendotheliosis virus and avian leukosis-sarcoma virus."} {"id": "PMID:167115", "title": "Protein synthesis in Sendai virus-infected cells.", "content": "The rate of protein synthesis in chicken embryo cells infected with Sendai virus 18 to 20 h previously was about two times greater than in mock-infected controls. At this time of infection six stable virus-induced proteins, four major structural proteins (P, NH, NP and M) and two non-structural proteins (28K and 61K), were identified by electrophoresis in SDS-polyacrylamide gel of total cell extracts. The structural glycopeptide F was not detected in the infected cell extracts. Pulse-chase experiments showed that PN NP, M and 28K proteins either did not undergo any post-translational processing or the processing occurred very rapidly. By contrast, a glycopeptide NH was apparently derived from one of two unstable precursons, 69K or 63K, which were revealed only after a short pulse. The synthesis of virus-specific proteins appeared to be regulated since its rate varied for individual classes of proteins. In nucleocapsid-particles isolated from infected cells two major structural proteins (P and NP) were found. A minor component with a very large mol. wt. was revealed in these particles as well as in the virus particle.", "contents": "Protein synthesis in Sendai virus-infected cells. The rate of protein synthesis in chicken embryo cells infected with Sendai virus 18 to 20 h previously was about two times greater than in mock-infected controls. At this time of infection six stable virus-induced proteins, four major structural proteins (P, NH, NP and M) and two non-structural proteins (28K and 61K), were identified by electrophoresis in SDS-polyacrylamide gel of total cell extracts. The structural glycopeptide F was not detected in the infected cell extracts. Pulse-chase experiments showed that PN NP, M and 28K proteins either did not undergo any post-translational processing or the processing occurred very rapidly. By contrast, a glycopeptide NH was apparently derived from one of two unstable precursons, 69K or 63K, which were revealed only after a short pulse. The synthesis of virus-specific proteins appeared to be regulated since its rate varied for individual classes of proteins. In nucleocapsid-particles isolated from infected cells two major structural proteins (P and NP) were found. A minor component with a very large mol. wt. was revealed in these particles as well as in the virus particle."} {"id": "PMID:167116", "title": "Early alteration of poliovirus in infected cells and its specific inhibition.", "content": "HeLa cells infected with radioactive poliovirus type 2 were disrupted with ultrasonic treatment, followed by addition of a non-ionic detergent. Two types of virus particles were found to sediment at 80 to 90% the rate of native virus. The first of these appeared to be a complex of native virus particles and membrane components, since treatment with 0-2% SDS released infectious native particles. The second was non-infectious and its sedimentation rate was not greatly altered by SDS. One hour after infection this non-infectious particle was the major product of cell-mediated eclipse. We have confirmed that 10 to 30 mg-g/ml S-7, a substituted thiopyrimidine, blocks infection of cells by poliovirus in a specific manner. Analysis of cells infected with radioactive poliovirus type 2 in the presence of S-7 showed that the virus particles remained as the complex which can be disrupted with SDS. In addition to blocking cell-mediated eclipse, S-7 stabilizes poliovirus against heat inactivation in vitro at the same concentrations which block infection. This action resembles the effect of 10-2 M-glutathione, which is also known to block cell-mediated eclipse of poliovirus.", "contents": "Early alteration of poliovirus in infected cells and its specific inhibition. HeLa cells infected with radioactive poliovirus type 2 were disrupted with ultrasonic treatment, followed by addition of a non-ionic detergent. Two types of virus particles were found to sediment at 80 to 90% the rate of native virus. The first of these appeared to be a complex of native virus particles and membrane components, since treatment with 0-2% SDS released infectious native particles. The second was non-infectious and its sedimentation rate was not greatly altered by SDS. One hour after infection this non-infectious particle was the major product of cell-mediated eclipse. We have confirmed that 10 to 30 mg-g/ml S-7, a substituted thiopyrimidine, blocks infection of cells by poliovirus in a specific manner. Analysis of cells infected with radioactive poliovirus type 2 in the presence of S-7 showed that the virus particles remained as the complex which can be disrupted with SDS. In addition to blocking cell-mediated eclipse, S-7 stabilizes poliovirus against heat inactivation in vitro at the same concentrations which block infection. This action resembles the effect of 10-2 M-glutathione, which is also known to block cell-mediated eclipse of poliovirus."} {"id": "PMID:167117", "title": "Characterization of adenovirus antibodies by single radial diffusion in agarose gels containing immobilized intact virus particles.", "content": "The interaction between antibodies and surface antigens of intact immobilized adenovirus particles was studied by single radial immunodiffusion tests (SRDT) in agarose gels. Purified virus particles and antisera against virus particles of selected serotypes representing different subgroups and against structural components of certain serotypes were employed. Antibodies against hexons, pentons and fibres all gave visible zones. Antisera against the latter components were more efficient in forming zones and this was though to be due to the occurrence of relatively smaller amounts of vertex capsomers and fibre antigen at the virus particle surface. The capacity of antibodies against vertex capsomers to form zones was demonstrated in tests with virus particles of intermediate types. The SRDT with immobilized virus particles was found to be highly sensitive for the demonstration of virus particle surface antigens shared between serotypes. Results obtained in previous studies using virus particles haemagglutination-inhibition (HI) tests including anti-antiserum were confirmed. Cross-reactions mainly occurred within subgroups and were ascribed to a sharing of vertex capsomere antigens. In preliminary studies a rapid typing was achieved by examination of paired human sera from five cases of adenovirus infections.", "contents": "Characterization of adenovirus antibodies by single radial diffusion in agarose gels containing immobilized intact virus particles. The interaction between antibodies and surface antigens of intact immobilized adenovirus particles was studied by single radial immunodiffusion tests (SRDT) in agarose gels. Purified virus particles and antisera against virus particles of selected serotypes representing different subgroups and against structural components of certain serotypes were employed. Antibodies against hexons, pentons and fibres all gave visible zones. Antisera against the latter components were more efficient in forming zones and this was though to be due to the occurrence of relatively smaller amounts of vertex capsomers and fibre antigen at the virus particle surface. The capacity of antibodies against vertex capsomers to form zones was demonstrated in tests with virus particles of intermediate types. The SRDT with immobilized virus particles was found to be highly sensitive for the demonstration of virus particle surface antigens shared between serotypes. Results obtained in previous studies using virus particles haemagglutination-inhibition (HI) tests including anti-antiserum were confirmed. Cross-reactions mainly occurred within subgroups and were ascribed to a sharing of vertex capsomere antigens. In preliminary studies a rapid typing was achieved by examination of paired human sera from five cases of adenovirus infections."} {"id": "PMID:167118", "title": "A genetic recombination map of foot-and-mouth disease virus.", "content": "Sixty ts mutants were isolated from the Pacheco strain of type O foot-and-mouth disease virus after treatment with either 5-fluorouracil or hydroxylamine. The conditions affecting recombination and assay of the ts+ recombinants were standardized. Using two ts mutants resistant to guanidine, three-factor crosses, supported by two-factor crosses, located 34 of the mutations in a linear arrangement. The recombination frequencies between certain pairs of mutations were additive. The guanidine character of the two resistant mutants mapped as a single site mutation and was located near the middle of the map.", "contents": "A genetic recombination map of foot-and-mouth disease virus. Sixty ts mutants were isolated from the Pacheco strain of type O foot-and-mouth disease virus after treatment with either 5-fluorouracil or hydroxylamine. The conditions affecting recombination and assay of the ts+ recombinants were standardized. Using two ts mutants resistant to guanidine, three-factor crosses, supported by two-factor crosses, located 34 of the mutations in a linear arrangement. The recombination frequencies between certain pairs of mutations were additive. The guanidine character of the two resistant mutants mapped as a single site mutation and was located near the middle of the map."} {"id": "PMID:167119", "title": "Chromatographic studies on picornavirus capsid polypeptides.", "content": "The polypeptides of encephalomyocarditis, Mouse-Elberfeld and type 5 rhinoviruses behave similarly when chromatographed on calcium phosphate (brushite), each being eluted by a linear phosphate buffer gradient containing sodium dodecyl sulphate in three major peaks, CI, C2 and C3. Analysis of the peaks by polyacrylamide gel electrophoresis suggests that the major capsid polypeptides of these three picornaviruses elute in the order: delta (peak CI), gamma with (peak C2) and alpha (peak C3).", "contents": "Chromatographic studies on picornavirus capsid polypeptides. The polypeptides of encephalomyocarditis, Mouse-Elberfeld and type 5 rhinoviruses behave similarly when chromatographed on calcium phosphate (brushite), each being eluted by a linear phosphate buffer gradient containing sodium dodecyl sulphate in three major peaks, CI, C2 and C3. Analysis of the peaks by polyacrylamide gel electrophoresis suggests that the major capsid polypeptides of these three picornaviruses elute in the order: delta (peak CI), gamma with (peak C2) and alpha (peak C3)."} {"id": "PMID:167120", "title": "Efficacy of exogenous interferon treatment initiated after onset of multiplication of vesicular stomatitis virus in the brains of mice.", "content": "Initiation of treatment with potent interferon preparations (6-4 x 10-6 units per dose) 4 days after intranasal inoculation of VSV (at a time when virus has already multiplied in the brains of most mice) resulted in a marked increase in mouse survival. In a series of 6 experiments only 11 to 18% of control mice survived whereas 52% of interferon treated mice survival. These results suggest the usefulness of exogenous interferon even when treatment is begun late in the course of an acute virus disease.", "contents": "Efficacy of exogenous interferon treatment initiated after onset of multiplication of vesicular stomatitis virus in the brains of mice. Initiation of treatment with potent interferon preparations (6-4 x 10-6 units per dose) 4 days after intranasal inoculation of VSV (at a time when virus has already multiplied in the brains of most mice) resulted in a marked increase in mouse survival. In a series of 6 experiments only 11 to 18% of control mice survived whereas 52% of interferon treated mice survival. These results suggest the usefulness of exogenous interferon even when treatment is begun late in the course of an acute virus disease."} {"id": "PMID:167121", "title": "The lact of antiviral effect of (polyinosinic acid): (polycytidylic acid) when attached to insoluble supports.", "content": "A local antiviral effect can be observed when (poly rI)-(poly rC), bound to Visking discs by u.v. irradiation, is incubated with monolayers of human foreskin fibroblast cells. Radioactive labelling of cytosine residues in (poly rI)-(poly rC) with -125I, has provided a much more sensitive method for determining the fate of the insoluble (poly rI)-(poly rC) than has been available hitherto. The antiviral effect is not related to the amount of (poly rI)-(POLY RC) present on the insoluble support but rather to the amount of polynucleotide lost from the support during incubation. Treatment of (poly rI)-(poly rC) which had been bound to cyanogen bromide-activated Sepharose with eigher dilute alkali or pancreatic ribonuclease released virtually all the polynucleotide. A small amount of (poly rI)-(poly rC) is released from the insoluble matrix in the presence of serum-free Minimum Eagle's Medium.", "contents": "The lact of antiviral effect of (polyinosinic acid): (polycytidylic acid) when attached to insoluble supports. A local antiviral effect can be observed when (poly rI)-(poly rC), bound to Visking discs by u.v. irradiation, is incubated with monolayers of human foreskin fibroblast cells. Radioactive labelling of cytosine residues in (poly rI)-(poly rC) with -125I, has provided a much more sensitive method for determining the fate of the insoluble (poly rI)-(poly rC) than has been available hitherto. The antiviral effect is not related to the amount of (poly rI)-(POLY RC) present on the insoluble support but rather to the amount of polynucleotide lost from the support during incubation. Treatment of (poly rI)-(poly rC) which had been bound to cyanogen bromide-activated Sepharose with eigher dilute alkali or pancreatic ribonuclease released virtually all the polynucleotide. A small amount of (poly rI)-(poly rC) is released from the insoluble matrix in the presence of serum-free Minimum Eagle's Medium."} {"id": "PMID:167130", "title": "Degeneration of muscle in association with carcinoma of the bronchus.", "content": "The clinical features and necropsy findings are described in three cases in which severe and rapidly progressive muscle weakness developed in association with carcinoma of the bronchus. In all three cases, muscular weakness was directly responsible for death. Histological and ultramicroscopical examination in all cases showed an unusual type of degeneration of muscle fibres accompanied by degeneration of intramuscular nerve fibres, but without involvement of the central nervous system, or of the peripheral nerve trunks. The findings are compared with those of previously reported cases, and possible mechanisms for the muscle degeneration are discussed.", "contents": "Degeneration of muscle in association with carcinoma of the bronchus. The clinical features and necropsy findings are described in three cases in which severe and rapidly progressive muscle weakness developed in association with carcinoma of the bronchus. In all three cases, muscular weakness was directly responsible for death. Histological and ultramicroscopical examination in all cases showed an unusual type of degeneration of muscle fibres accompanied by degeneration of intramuscular nerve fibres, but without involvement of the central nervous system, or of the peripheral nerve trunks. The findings are compared with those of previously reported cases, and possible mechanisms for the muscle degeneration are discussed."} {"id": "PMID:167131", "title": "Intranuclear \"paramyxovirus-like\" material in multiple sclerosis, adreno-leukodystrophy and Kuf's disease.", "content": "Detailed comparative ultrastructural examination of multiple sclerosis (MS) plaques, inflammatory CNS lesions from adreno-leukodystrophy(A-LD), tissue from a case of chronic granulomatous meningitis, biopsy samples of necrotic cerebral cortex and CNS tissue from a case of Kuf's disease (adult-type ceroid lipofuscinosis), has revealed that the intranuclear filamentous material previously thought to be related to a viral infection in MS is a non-specific finding. These intranuclear strands were, however, found in greatest frequency in the acute lesions of MS and were absent from chronically demyelinated areas. The macrophages, lymphocytes and fibrocytes containing filamentous material in the nuclei were mainly perivascular. In A-LD, some macrophages in active lesions contained similar nuclei, and in Kuf's disease they were present in some glial cells in the cerebral cortex.", "contents": "Intranuclear \"paramyxovirus-like\" material in multiple sclerosis, adreno-leukodystrophy and Kuf's disease. Detailed comparative ultrastructural examination of multiple sclerosis (MS) plaques, inflammatory CNS lesions from adreno-leukodystrophy(A-LD), tissue from a case of chronic granulomatous meningitis, biopsy samples of necrotic cerebral cortex and CNS tissue from a case of Kuf's disease (adult-type ceroid lipofuscinosis), has revealed that the intranuclear filamentous material previously thought to be related to a viral infection in MS is a non-specific finding. These intranuclear strands were, however, found in greatest frequency in the acute lesions of MS and were absent from chronically demyelinated areas. The macrophages, lymphocytes and fibrocytes containing filamentous material in the nuclei were mainly perivascular. In A-LD, some macrophages in active lesions contained similar nuclei, and in Kuf's disease they were present in some glial cells in the cerebral cortex."} {"id": "PMID:167132", "title": "Cerebral sponginess and GM3 gangliosidosis; ultrastructure and probable pathogenesis.", "content": "Extensive multifocal vacuolation of the cerebral hemispheres, brain stem, cerebellum, optic nerves and spinal cord were demonstrated in a 3 1/2 month-old infant. This co-existed with marked increases in cerebral and hepatic ganglioside GM3 (hematoside), absence of its higher homologues (GM1 and GM2) and absence of tissue N-acetylgalactosaminyl transferase. Ultrastructurally, there are major abnormalities in myelin and astroglia. The absence of identifiable \"storage\" material is believed to correlate with an enzymatic defect involved in ganglioside anabolism. A familial occurrence of this disorder is strongly suggested by the clinical history.", "contents": "Cerebral sponginess and GM3 gangliosidosis; ultrastructure and probable pathogenesis. Extensive multifocal vacuolation of the cerebral hemispheres, brain stem, cerebellum, optic nerves and spinal cord were demonstrated in a 3 1/2 month-old infant. This co-existed with marked increases in cerebral and hepatic ganglioside GM3 (hematoside), absence of its higher homologues (GM1 and GM2) and absence of tissue N-acetylgalactosaminyl transferase. Ultrastructurally, there are major abnormalities in myelin and astroglia. The absence of identifiable \"storage\" material is believed to correlate with an enzymatic defect involved in ganglioside anabolism. A familial occurrence of this disorder is strongly suggested by the clinical history."} {"id": "PMID:167133", "title": "Gemistocytic astrocytes in gliomas. An autoradiographic study.", "content": "Tritiated thymidine (3-H-T) was administered intravenously to seven patients with cerebral gliomas. Autoradiographs of biopsy specimens excised within the next four hours and of autopsy specimens from three of these patients obtained three weeks to six months after the single pulse of 3-H-T revealed the following: (a) no gemistocytic astrocytes and only a few giant astrocytes were labeled in biopsy specimens, despite a high overall labeling index of 5-10% (percentage of cells labeled in the total cell population); and (b) scattered foci of labeled genistocytes occurred in autopsy specimens, despite a sharp drop in overall labeling index. In histologic sections of these same specimens, genistocytes and giant cells occurred as the major cell types in an irradiated tumor, in large clusters near foci of degeneration, and as isolated cells in anaplastic foci. These findings suggest that: 1) gemistocytes and giant astrocytes are similar in origin and growth potential regardless of minor variations in morphology; 2) these cells multiply slowly, if at all, and are closely related to regressive changes within the tumor; 3) these cells may reflect profound proliferative activity in adjacent neoplastic cells; and 4) the labeling index and malignant potential of the tumor as a whole depend upon the more rapidly dividing tumor elements. Thus, if genistocytes and giant cells indicate malignancy, they do so secondarily, and the biologically harmless gemistocyte may be the loser in an intense competition for the substrates needed in cell proliferation.", "contents": "Gemistocytic astrocytes in gliomas. An autoradiographic study. Tritiated thymidine (3-H-T) was administered intravenously to seven patients with cerebral gliomas. Autoradiographs of biopsy specimens excised within the next four hours and of autopsy specimens from three of these patients obtained three weeks to six months after the single pulse of 3-H-T revealed the following: (a) no gemistocytic astrocytes and only a few giant astrocytes were labeled in biopsy specimens, despite a high overall labeling index of 5-10% (percentage of cells labeled in the total cell population); and (b) scattered foci of labeled genistocytes occurred in autopsy specimens, despite a sharp drop in overall labeling index. In histologic sections of these same specimens, genistocytes and giant cells occurred as the major cell types in an irradiated tumor, in large clusters near foci of degeneration, and as isolated cells in anaplastic foci. These findings suggest that: 1) gemistocytes and giant astrocytes are similar in origin and growth potential regardless of minor variations in morphology; 2) these cells multiply slowly, if at all, and are closely related to regressive changes within the tumor; 3) these cells may reflect profound proliferative activity in adjacent neoplastic cells; and 4) the labeling index and malignant potential of the tumor as a whole depend upon the more rapidly dividing tumor elements. Thus, if genistocytes and giant cells indicate malignancy, they do so secondarily, and the biologically harmless gemistocyte may be the loser in an intense competition for the substrates needed in cell proliferation."} {"id": "PMID:167134", "title": "The third circulation revisited.", "content": "The author reviews modern information concerning the formation, flow and functions of the cerebrospinal fluid. Particular attention is given to the lymphatic-like features of the third circulation and to its importance as an internal milieu for nervous tissue.", "contents": "The third circulation revisited. The author reviews modern information concerning the formation, flow and functions of the cerebrospinal fluid. Particular attention is given to the lymphatic-like features of the third circulation and to its importance as an internal milieu for nervous tissue."} {"id": "PMID:167135", "title": "Continuous intraventricular cerebrospinal fluid pressure recording in hydrocephalic children during wakefulness and sleep.", "content": "Continuous 24-hour recordings of intracranial pressure and electroencephalographic activity were made on five hydrocephalic children in whom, in the resting wakefulness state, the intracranial pressure (ICP) was considered normal. An increase in both the mean ICP and its oscillations related to cardiac systole was recorded during slow-wave sleep. Further episodic increases, up to a factor of 7 compared to wakefulness values, occurred during sleep. In three patients it was possible to correlate such episodic increases to the rapid eye movement phases of sleep. The authors discuss these phenomena and their possible implication in the progression of hydrocephalus.", "contents": "Continuous intraventricular cerebrospinal fluid pressure recording in hydrocephalic children during wakefulness and sleep. Continuous 24-hour recordings of intracranial pressure and electroencephalographic activity were made on five hydrocephalic children in whom, in the resting wakefulness state, the intracranial pressure (ICP) was considered normal. An increase in both the mean ICP and its oscillations related to cardiac systole was recorded during slow-wave sleep. Further episodic increases, up to a factor of 7 compared to wakefulness values, occurred during sleep. In three patients it was possible to correlate such episodic increases to the rapid eye movement phases of sleep. The authors discuss these phenomena and their possible implication in the progression of hydrocephalus."} {"id": "PMID:167136", "title": "Radiation of infratentorial and supratentorial brain-stem tumors.", "content": "A retrospective survey of 41 patients with unbiopsied thalamic, pontine, and medullary tumors treated with radiation therapy demonstrated 30% to 40% 3-year survival, with seven long-term survivors. Eleven of the 12 patients surviving over 3 years have essentially normal neurological function. Of seven patients in whom histological diagnoses were eventually obtained, four proved to have glioblastomas and three low-grade astrocytomas. Autopsy revealed that all glioblastomatous tumors extended beyond the treatment field; this suggested that larger volumes, perhaps the whole brain, should be irradiated. High doses (at least 5000 rads) should be used since the 3-year survival among those receiving such doses was 45%.", "contents": "Radiation of infratentorial and supratentorial brain-stem tumors. A retrospective survey of 41 patients with unbiopsied thalamic, pontine, and medullary tumors treated with radiation therapy demonstrated 30% to 40% 3-year survival, with seven long-term survivors. Eleven of the 12 patients surviving over 3 years have essentially normal neurological function. Of seven patients in whom histological diagnoses were eventually obtained, four proved to have glioblastomas and three low-grade astrocytomas. Autopsy revealed that all glioblastomatous tumors extended beyond the treatment field; this suggested that larger volumes, perhaps the whole brain, should be irradiated. High doses (at least 5000 rads) should be used since the 3-year survival among those receiving such doses was 45%."} {"id": "PMID:167137", "title": "Effect of dietary fat and sucrose on the activities of several rat hepatic enzymes and their diurnal response to a meal.", "content": "Regulation of the cytoplasmic enzymes, pyruvate kinase (PK), glucokinase (GK), phosphoenolpy ruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), ATP citrate-lyase (ATP-CL), NAD-malate dehydrogenase (NAD-MD), NADP-malate dehydrogenase (NADP-MD), glutamic-pyruvic transaminase (GPT), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD), in rat liver by dietary fat (F diet) and dietary sucrose (S diet) was investigated. Mealfeeding the S diet to adult rats for 5 and 9 months resulted in a diurnal dietary response (i.e., food response) variation of FDP, GK, ATP-CL, 6PGD, and PK, while meal-feeding the S diet to young rats resulted in diurnal dietary response variation of ATP-CL, G6PD, NADP-MD, 6PGD, GPT, and PK. Meal-feeding the fat diet results in essentially no diurnal variation in enzyme activity. The overall effect of meal-feeding, as compared with ad libitum feeding, of the S diet was to increase the levels of G6PD, ATP-CL, and NADP-MD and to decrease the level of PEck in the meal-fed rats. Young rats meal-fed the two diets have higher enzyme activities than meal-fed adult rats for the observed enzymes (except for GPT and NAD-MD). In general, hepatic levels of the enzymes studied are low in the F diet-fed animals and markedly higher for the S diet-fed animals. These results suggest that dietary carbohydrate specifically induces those enzymes involved in carbohydrate metabolism, whereas dietary fat does not affect their levels. On the basis of prior evidence for an early requirement of RNA synthesis for sucrose induction of G6PD, this widespread induction of liver enzymes by carbohydrate must indicate either increased synthesis of ribosomal RNA with later regulation of synthesis specifically of these enzymes or increased synthesis of a rather large group of specific messenger RNAs i.e., coordinate genetic control of a number of these enzyme messenger RNAs.", "contents": "Effect of dietary fat and sucrose on the activities of several rat hepatic enzymes and their diurnal response to a meal. Regulation of the cytoplasmic enzymes, pyruvate kinase (PK), glucokinase (GK), phosphoenolpy ruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), ATP citrate-lyase (ATP-CL), NAD-malate dehydrogenase (NAD-MD), NADP-malate dehydrogenase (NADP-MD), glutamic-pyruvic transaminase (GPT), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD), in rat liver by dietary fat (F diet) and dietary sucrose (S diet) was investigated. Mealfeeding the S diet to adult rats for 5 and 9 months resulted in a diurnal dietary response (i.e., food response) variation of FDP, GK, ATP-CL, 6PGD, and PK, while meal-feeding the S diet to young rats resulted in diurnal dietary response variation of ATP-CL, G6PD, NADP-MD, 6PGD, GPT, and PK. Meal-feeding the fat diet results in essentially no diurnal variation in enzyme activity. The overall effect of meal-feeding, as compared with ad libitum feeding, of the S diet was to increase the levels of G6PD, ATP-CL, and NADP-MD and to decrease the level of PEck in the meal-fed rats. Young rats meal-fed the two diets have higher enzyme activities than meal-fed adult rats for the observed enzymes (except for GPT and NAD-MD). In general, hepatic levels of the enzymes studied are low in the F diet-fed animals and markedly higher for the S diet-fed animals. These results suggest that dietary carbohydrate specifically induces those enzymes involved in carbohydrate metabolism, whereas dietary fat does not affect their levels. On the basis of prior evidence for an early requirement of RNA synthesis for sucrose induction of G6PD, this widespread induction of liver enzymes by carbohydrate must indicate either increased synthesis of ribosomal RNA with later regulation of synthesis specifically of these enzymes or increased synthesis of a rather large group of specific messenger RNAs i.e., coordinate genetic control of a number of these enzyme messenger RNAs."} {"id": "PMID:167138", "title": "Ultrastructure of gastointestinal smooth muscle in ducks with a vitamin E-selenium deficiency.", "content": "The earliest ultrastructural lesions involving smooth muscle of duck duodenum and gizzard produced by a vitamin E-selenium deficiency were a degereration of sarcoplasmic reticulum and mitochondria. Lysosomes were not observed during these earliest alterations of deficient smooth muscle. Lipid droplets and mineral deposits were present in more severely degernerating smooth muscle that was being infiltrated by heterophils. In areas of necrotic smooth muscle, myoblasts were forming while macrophages, fibroblasts, and an occasional syncytial giant cell contained lipid droplets and surrounded coalesced mineral crystals. Endothelial cells of capillaries and stromal connective tissue were less severely affected with lesions developing after the earliest signs of smooth muscle degeneration. Neuroaxonal degeneration of nonmyelinated nerve fibers was not observed until after most of the smooth muscle had undergone either degeneration or necrosis. A possible explanation for the pathogenesis of the smooth muscle necrosis is discussed in light of the ultrastructural findings.", "contents": "Ultrastructure of gastointestinal smooth muscle in ducks with a vitamin E-selenium deficiency. The earliest ultrastructural lesions involving smooth muscle of duck duodenum and gizzard produced by a vitamin E-selenium deficiency were a degereration of sarcoplasmic reticulum and mitochondria. Lysosomes were not observed during these earliest alterations of deficient smooth muscle. Lipid droplets and mineral deposits were present in more severely degernerating smooth muscle that was being infiltrated by heterophils. In areas of necrotic smooth muscle, myoblasts were forming while macrophages, fibroblasts, and an occasional syncytial giant cell contained lipid droplets and surrounded coalesced mineral crystals. Endothelial cells of capillaries and stromal connective tissue were less severely affected with lesions developing after the earliest signs of smooth muscle degeneration. Neuroaxonal degeneration of nonmyelinated nerve fibers was not observed until after most of the smooth muscle had undergone either degeneration or necrosis. A possible explanation for the pathogenesis of the smooth muscle necrosis is discussed in light of the ultrastructural findings."} {"id": "PMID:167144", "title": "Capsular and vascular invasion: important prognostic factors in Wilms' tumor.", "content": "The influence of capsular and vascular invasion on prognosis was determined retrospectively in 52 children with Wilms' tumor. Local recurrence was more prevalent (0.26) in patients with rupture or capsular invasion than in any other group. Inadequate postnephrectomy irradiation or infiltration of the liver by nephroblastoma cells appeared to be predisposing factors in the development of these reccurrences. Of the 26 patients with gross or microscopic vascular invasion, 13 developed metastasis. This proportion was significantly higher than in patients without vascular involvement (p less than 0.05). These observations emphasize the importance of microscopic detection of capsular and vascular invasion in staging of Wilm's tumor.", "contents": "Capsular and vascular invasion: important prognostic factors in Wilms' tumor. The influence of capsular and vascular invasion on prognosis was determined retrospectively in 52 children with Wilms' tumor. Local recurrence was more prevalent (0.26) in patients with rupture or capsular invasion than in any other group. Inadequate postnephrectomy irradiation or infiltration of the liver by nephroblastoma cells appeared to be predisposing factors in the development of these reccurrences. Of the 26 patients with gross or microscopic vascular invasion, 13 developed metastasis. This proportion was significantly higher than in patients without vascular involvement (p less than 0.05). These observations emphasize the importance of microscopic detection of capsular and vascular invasion in staging of Wilm's tumor."} {"id": "PMID:167147", "title": "Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity.", "content": "Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg.", "contents": "Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity. Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg."} {"id": "PMID:167148", "title": "Effects of verapamil on myocardial contractility, cardiac adenosine 3,'5'-monophosphate and heart phosphorylase.", "content": "The effects of verapamil on myocardial isometric force on contraction, cardiac adenosine 3,'5'-monophosphate (cyclic AMP) and heart phosphorylase alpha activity were studied in the isolated perfused rat heart. When hearts were perfused with verapamil (5.98 times 10- minus 8 M), force of contraction was reduced approximately 50% within 4 to 5 minutes; at this point, the concentration of cyclic AMP was significantly lower than control but phosphorylase alpha activity was unchanged. In hearts perfused continuously for 60 minutes with verapamil, force of contraction and cyclic AMP levels returned to normal within 20 minutes after administration of verapamil was begun. Isoproterenol (0.355 nmol/min) reversed the depressant effect of verapamil on cardiac contractility and restored heart cyclic AMP levels to normal. Methoxamine (35.5 nmol/min) given to verapamil-depressed hearts, caused contractile force to return to normal, but cardiac cyclic AMP levels remained low. Mephentermine (23.0 nmol/min) had no effect on cardiac contraction, cyclic AMP or phosphorylase alpha activity in hearts depressed by verapamil. It was concluded that with the concentration of verapamil used in these experiments, the drug caused a transient decrease in force of contraction and myocardial cyclic AMP. Both the depression in myocardial contractility and in cardiac cyclic AMP caused by verapamil were reversed promptly by isoproterenol, whereas methoxamine overcame acutely only the negative inotropic effect of verapamil. Mephentermine had no effect on hearts depressed by verapamil.", "contents": "Effects of verapamil on myocardial contractility, cardiac adenosine 3,'5'-monophosphate and heart phosphorylase. The effects of verapamil on myocardial isometric force on contraction, cardiac adenosine 3,'5'-monophosphate (cyclic AMP) and heart phosphorylase alpha activity were studied in the isolated perfused rat heart. When hearts were perfused with verapamil (5.98 times 10- minus 8 M), force of contraction was reduced approximately 50% within 4 to 5 minutes; at this point, the concentration of cyclic AMP was significantly lower than control but phosphorylase alpha activity was unchanged. In hearts perfused continuously for 60 minutes with verapamil, force of contraction and cyclic AMP levels returned to normal within 20 minutes after administration of verapamil was begun. Isoproterenol (0.355 nmol/min) reversed the depressant effect of verapamil on cardiac contractility and restored heart cyclic AMP levels to normal. Methoxamine (35.5 nmol/min) given to verapamil-depressed hearts, caused contractile force to return to normal, but cardiac cyclic AMP levels remained low. Mephentermine (23.0 nmol/min) had no effect on cardiac contraction, cyclic AMP or phosphorylase alpha activity in hearts depressed by verapamil. It was concluded that with the concentration of verapamil used in these experiments, the drug caused a transient decrease in force of contraction and myocardial cyclic AMP. Both the depression in myocardial contractility and in cardiac cyclic AMP caused by verapamil were reversed promptly by isoproterenol, whereas methoxamine overcame acutely only the negative inotropic effect of verapamil. Mephentermine had no effect on hearts depressed by verapamil."} {"id": "PMID:167149", "title": "Dose-response relationships for arginine vasopressin and synthetic analogs on three types of rat blood vessels: possible evidence for regional differences in vasopressin receptor sites within a mammal.", "content": "These experiments were undertaken to determine the comparative relationships between chemical structure and biologic (contractile) activity of a series of vasopressin hormone analogs on different rat blood vessels (e.g., aorta, mesenteric arteriole and mesenteric venule). The functional contributions to, and interactions with, phenolic hydroxyl and aromatic groups as well as basicity in positions 2, 3 and 8, respectively, to or with hormone-receptor affinity and intrinsic (contractile) activity, were determined by analyzing the dose-response curves of five vasopressin peptides lacking one or more of these functional groups. The findings demonstrate that: 1) the structure-action relationships for vasopressin peptide-induced contractions on rat blood vessels vary with the particular type of macro- or microvessel (i.e., aorta, arteriole and venule); 2) the phenolic and aromatic groups in positions 2 and 3, respectively, are not only important for hormone-receptor affinity but intrinsic activity as well; 3) the potency (EC50) values for arginine vasopressin as well as the potencies and intrinsic activities of synthetic vasopressin analogs varied between the three different types of rat blood vessels examined; and 4) circulating levels (i.e., 10- minus 11- minus 10- minus 12 M) of [8-arginine]-vasopressin are capable of inducing contractile effects on mesenteric arterioles and venules. The quantitative data obtained in this study support the notion that a heterogeneity of the receptor, which subserves contraction, probably exists in blood vessels within and between vascular beds of a single mammalian species.", "contents": "Dose-response relationships for arginine vasopressin and synthetic analogs on three types of rat blood vessels: possible evidence for regional differences in vasopressin receptor sites within a mammal. These experiments were undertaken to determine the comparative relationships between chemical structure and biologic (contractile) activity of a series of vasopressin hormone analogs on different rat blood vessels (e.g., aorta, mesenteric arteriole and mesenteric venule). The functional contributions to, and interactions with, phenolic hydroxyl and aromatic groups as well as basicity in positions 2, 3 and 8, respectively, to or with hormone-receptor affinity and intrinsic (contractile) activity, were determined by analyzing the dose-response curves of five vasopressin peptides lacking one or more of these functional groups. The findings demonstrate that: 1) the structure-action relationships for vasopressin peptide-induced contractions on rat blood vessels vary with the particular type of macro- or microvessel (i.e., aorta, arteriole and venule); 2) the phenolic and aromatic groups in positions 2 and 3, respectively, are not only important for hormone-receptor affinity but intrinsic activity as well; 3) the potency (EC50) values for arginine vasopressin as well as the potencies and intrinsic activities of synthetic vasopressin analogs varied between the three different types of rat blood vessels examined; and 4) circulating levels (i.e., 10- minus 11- minus 10- minus 12 M) of [8-arginine]-vasopressin are capable of inducing contractile effects on mesenteric arterioles and venules. The quantitative data obtained in this study support the notion that a heterogeneity of the receptor, which subserves contraction, probably exists in blood vessels within and between vascular beds of a single mammalian species."} {"id": "PMID:167150", "title": "Muscarinic cholinergic regulation of cyclic guanosine 3,5-monophosphate in autonomic ganglia: possible role in synaptic transmission.", "content": "The effects of acetylcholine, and of agents which selectively mimic or block its nicotinic and muscarinic actions, have been studied on the levels of guanosine 3,5-monophosphate (cyclic GMP) and adenosine 3,5-monophosphate (cyclic AMP) in slices of bovine superior cervical ganglion. Low doses of either acetylcholine or the muscarinic agonist, bethanechol, caused a substantial increase in the level of cyclic GMP, and slightly increased the level of cyclic AMP; the acetylcholine- and the bethanechol-induced increases in cyclic GMP were blocked by atropine, the muscarinic antagonist, but not by hexamethonium, the nicotinic antagonist. The nicotinic agonist N,N-dimethylphenylpiperazinium did not alter the level of either of the cyclic nucleotides. Dopamine increased the level of cyclic AMP and acetylcholine partially prevented this dopamine-induced increase in cyclic AMP. The data are consistent with a model for the ganglion in which muscarinic cholinergic synaptic transmission is mediated by an increase in the level of cyclic GMP in the postganglionic neurons and dopaminergic transmission by an increase in the level of cyclic AMP in these neurons.", "contents": "Muscarinic cholinergic regulation of cyclic guanosine 3,5-monophosphate in autonomic ganglia: possible role in synaptic transmission. The effects of acetylcholine, and of agents which selectively mimic or block its nicotinic and muscarinic actions, have been studied on the levels of guanosine 3,5-monophosphate (cyclic GMP) and adenosine 3,5-monophosphate (cyclic AMP) in slices of bovine superior cervical ganglion. Low doses of either acetylcholine or the muscarinic agonist, bethanechol, caused a substantial increase in the level of cyclic GMP, and slightly increased the level of cyclic AMP; the acetylcholine- and the bethanechol-induced increases in cyclic GMP were blocked by atropine, the muscarinic antagonist, but not by hexamethonium, the nicotinic antagonist. The nicotinic agonist N,N-dimethylphenylpiperazinium did not alter the level of either of the cyclic nucleotides. Dopamine increased the level of cyclic AMP and acetylcholine partially prevented this dopamine-induced increase in cyclic AMP. The data are consistent with a model for the ganglion in which muscarinic cholinergic synaptic transmission is mediated by an increase in the level of cyclic GMP in the postganglionic neurons and dopaminergic transmission by an increase in the level of cyclic AMP in these neurons."} {"id": "PMID:167151", "title": "Effects of pharmacologic agents on release of lysosomal enzymes from alveolar mononuclear cells.", "content": "Several pharmacologic agents were tested for inhibition of phagocyte-induced release of lysosomal enzymes from guinea-pig alveolar mononuclear cells and peritoneal leukocytes. The activities of the lysosomal enzyme beta-glucuronidase and the cytoplasmic enzyme lactate dehydrogenase were determined in the cells and media following a 2-hour incubation period of cells and zymosan particles. Adrenergic and cholinergic agents, the 3,'5'-adenosine and guanosine cyclic nucleotides, and theophylline had no effect on phagocytosis or release of beta-glucuronidase or lactate dehydrogenase from alveolar cells. Cytochalasin B stimulated lysosomal but not cytoplasmic enzyme release from these cells in the absence of zymosan. Colchicine and hydrocortisone inhibited phagocytosis and beta-glucuronidase extrusion, and phenylbutazone inhibited only beta-glucuronidase release. Colchicine and phenylbutazone also inhibited enzyme release stimulated by cytochalasin B indicating that they were affecting postphagocytic events. The cyclic nucleotides and theophylline were without effect on the peritoneal leukocytes; dexamethasone and phenylbutazone inhibited enzyme release with only the former antagonizing phagocytosis.", "contents": "Effects of pharmacologic agents on release of lysosomal enzymes from alveolar mononuclear cells. Several pharmacologic agents were tested for inhibition of phagocyte-induced release of lysosomal enzymes from guinea-pig alveolar mononuclear cells and peritoneal leukocytes. The activities of the lysosomal enzyme beta-glucuronidase and the cytoplasmic enzyme lactate dehydrogenase were determined in the cells and media following a 2-hour incubation period of cells and zymosan particles. Adrenergic and cholinergic agents, the 3,'5'-adenosine and guanosine cyclic nucleotides, and theophylline had no effect on phagocytosis or release of beta-glucuronidase or lactate dehydrogenase from alveolar cells. Cytochalasin B stimulated lysosomal but not cytoplasmic enzyme release from these cells in the absence of zymosan. Colchicine and hydrocortisone inhibited phagocytosis and beta-glucuronidase extrusion, and phenylbutazone inhibited only beta-glucuronidase release. Colchicine and phenylbutazone also inhibited enzyme release stimulated by cytochalasin B indicating that they were affecting postphagocytic events. The cyclic nucleotides and theophylline were without effect on the peritoneal leukocytes; dexamethasone and phenylbutazone inhibited enzyme release with only the former antagonizing phagocytosis."} {"id": "PMID:167152", "title": "Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction.", "content": "1. End-plate currents have been studied in gylcerol-treated frog sartorius nerve-muscle preparations with the voltage-clamp technique. 2. Adding the anticholinesterase prostigmine (3 muM) to the solution bathing the muscle caused a 2-7 (mean 3-3) times increase in the time constant of decay of end-plate currents. The anticholinesterase edrophonium (15 muM) also prolonged the time course of end-plate currents. 3. Pre-treatment of the preparation with collagenase, which leads to the removal of acetylcholinesterase in the synaptic cleft, prolongs the time course of end-plate currents. 4. Curare (1-2 muM), cobratoxin (0-13 muM), or alpha-bungarotoxin (0-13-0-26 muM) decreased the time constant of decay of end-plate currents in the presence of prostigmine. 5. These observations are consistant with the suggestion that repeated binding of acetylcholine (ACh) molecules to receptors as the ACh escapes from the synaptic cleft can contribute to the prolongation of end-plate currents which occurrs when acetylcholinesterase activity is eliminated. 6. Increasing the amount of transmitter released from the presynaptic nerve terminal leads to a prolongation of end-plate currents in the presence of prostigmine. 7. In the presence of prostigmine, the second of two end-plate currents (interval 2-10 msec) decays more slowly than the first. 8. ACh (1-40 muM) or carbachol (40 muM) applied in the solution bathing the muscle prolongs end-plate currents in the presence of prostigmine. 9. It is suggested on the basis of the observations described in paragraphs 6 to 8 that the time constant of decay of end-plate currents in the presence of prostigmine increases with increasing concentrations of ACh in the synaptic cleft. In the absence of prostigmine, increasing the concentration of ACh in the synaptic cleft did not change the time constant for decay of end-plate currents. 10. We interpret these results to suggest that ACh can have a cooperative action on receptors such that the association of ACh with one receptor (defined as binding a single ACh molecule) favours the binding or retention of ACh at other receptors. This implies that receptors can interact.", "contents": "Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction. 1. End-plate currents have been studied in gylcerol-treated frog sartorius nerve-muscle preparations with the voltage-clamp technique. 2. Adding the anticholinesterase prostigmine (3 muM) to the solution bathing the muscle caused a 2-7 (mean 3-3) times increase in the time constant of decay of end-plate currents. The anticholinesterase edrophonium (15 muM) also prolonged the time course of end-plate currents. 3. Pre-treatment of the preparation with collagenase, which leads to the removal of acetylcholinesterase in the synaptic cleft, prolongs the time course of end-plate currents. 4. Curare (1-2 muM), cobratoxin (0-13 muM), or alpha-bungarotoxin (0-13-0-26 muM) decreased the time constant of decay of end-plate currents in the presence of prostigmine. 5. These observations are consistant with the suggestion that repeated binding of acetylcholine (ACh) molecules to receptors as the ACh escapes from the synaptic cleft can contribute to the prolongation of end-plate currents which occurrs when acetylcholinesterase activity is eliminated. 6. Increasing the amount of transmitter released from the presynaptic nerve terminal leads to a prolongation of end-plate currents in the presence of prostigmine. 7. In the presence of prostigmine, the second of two end-plate currents (interval 2-10 msec) decays more slowly than the first. 8. ACh (1-40 muM) or carbachol (40 muM) applied in the solution bathing the muscle prolongs end-plate currents in the presence of prostigmine. 9. It is suggested on the basis of the observations described in paragraphs 6 to 8 that the time constant of decay of end-plate currents in the presence of prostigmine increases with increasing concentrations of ACh in the synaptic cleft. In the absence of prostigmine, increasing the concentration of ACh in the synaptic cleft did not change the time constant for decay of end-plate currents. 10. We interpret these results to suggest that ACh can have a cooperative action on receptors such that the association of ACh with one receptor (defined as binding a single ACh molecule) favours the binding or retention of ACh at other receptors. This implies that receptors can interact."} {"id": "PMID:167156", "title": "Studies on convulsants in the isolated frog spinal cord. II. Effects on root potentials.", "content": "1. In the isolated frog spinal cord picrotoxin, bicuculline, and strychnine were evaluated for their effects on synaptically induced root potentials recorded by the sucrose gap technique. 2. Picrotoxin (greater than 10- minus 4 M) completely blocked the dorsal root potential (DRP) elicited by stimulating the ventral root of the same segment (VR-DRP). Although picrotoxin antagonized the DRP elicited by stimulation of either an adjacent dorsal root (DR-DRP) or the lateral column (LC-DRP), a slower component to these potentials appeared and increased in size as the concentration of picrotoxin was increased. Thus picrotoxin brings out a later, picrotoxin resistant component to the DR-DRP and LC-DRP. 3. Strychnine (10- minus 8-10- minus 5 M) reduced and abolished the VR-DRP without prolongation and progressively increased and prolonged the DR-DRP (and LC-DRP) and the DR-VRP. Strychnine in higher concentrations (greater than 10- minus 4 M) also reduced the amplitude and prolonged the duration of the compound action potential of afferent fibres. 4. These results combined with those presented in the preceding paper (Barker, Nicoll & Padjen, 1975) suggest that (1) a GABA-like transmitter mediates the final step in the DR-DRP and LC-DRP pathways and that (2) either taurine or beta-alanine may mediate the last step in the VR-DRP pathway.", "contents": "Studies on convulsants in the isolated frog spinal cord. II. Effects on root potentials. 1. In the isolated frog spinal cord picrotoxin, bicuculline, and strychnine were evaluated for their effects on synaptically induced root potentials recorded by the sucrose gap technique. 2. Picrotoxin (greater than 10- minus 4 M) completely blocked the dorsal root potential (DRP) elicited by stimulating the ventral root of the same segment (VR-DRP). Although picrotoxin antagonized the DRP elicited by stimulation of either an adjacent dorsal root (DR-DRP) or the lateral column (LC-DRP), a slower component to these potentials appeared and increased in size as the concentration of picrotoxin was increased. Thus picrotoxin brings out a later, picrotoxin resistant component to the DR-DRP and LC-DRP. 3. Strychnine (10- minus 8-10- minus 5 M) reduced and abolished the VR-DRP without prolongation and progressively increased and prolonged the DR-DRP (and LC-DRP) and the DR-VRP. Strychnine in higher concentrations (greater than 10- minus 4 M) also reduced the amplitude and prolonged the duration of the compound action potential of afferent fibres. 4. These results combined with those presented in the preceding paper (Barker, Nicoll & Padjen, 1975) suggest that (1) a GABA-like transmitter mediates the final step in the DR-DRP and LC-DRP pathways and that (2) either taurine or beta-alanine may mediate the last step in the VR-DRP pathway."} {"id": "PMID:167157", "title": "The sensitivity of adrenal responses to synthetic adrenocorticotrophin in the conscious unrestrained calf.", "content": "1. Changes in cortisol and corticosterone output and blood flow from the adrenal gland have been determined in the conscious unrestrained calf during I.V. infusions of synthetic adrenocorticotrophin (Synacthen) at 0-5 ng-kg(-1) min- minus 1 (low dose), 5 ng-kg- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1(very high dose). 2. Infusions at the low dose produced a rise in adrenal output of both cortisol and corticosterone to maximum values of approximately 100 and 30 ng-kg- minus 1 min- minus 1 respectively. Mean output of both steroids was significantly increased within 5 min, reached a maximum within 10 min and had fallen to resting levels 10 min after the infusion was discontinued. 3. The effects of infusions at both the high and very high doses were closely similar; maximal cortisol outputs were within the range 600-800 ng-kg- minus 1 min- minus 1 and corticosterone 350-500 ng-kg- minus 1 min- minus 1 in both groups. 4. When the infusions were terminated, pronounced differences were observed in the rates at which steroid outputs declined. Basal levels were restored within 10 min following the low dose and within 60 min in medium dose animals, but both cortisol and corticosterone output were still elevated 2 hr after infusion in high dose animals. In calves infused at the very high dose, cortisol output did not fall significantly during 2 hr period. The ratio of cortisol: corticosterone released from the adrenal gland immediately before infusion (3-2 +/- 0-3) approximated to the proportions in which the two steroids were found in the arterial plasma, but fell progressively to a minimum (1-3 +/- 0-1) with increasing doses of Synacthen. Conversely, the ratio of the steroids in the arterial plasma was increased during infusions at the low dose, but not at the higher doses. 6. No significant change in adrenal blood flow occurred during Synacthen infusion in low dose animals despite the increase in steroid output. In medium dose animals blood flow through the gland rose during infusion by approximately 75 per cent while in both high and very high dose animals the flow increased by up to 300 percent. 7. In the three groups in which adrenal hyperaemia occurred, blood flow had fallen to within the resting range 45 min after infusion: in each case this fall was much more rapid than the fall in steroid output. No significant increase in aortic blood pressure or heart rate accompanied infusion of Synacthen, indicating that adrenal hyperaemia was dependent upon vasodilatation with the gland. 8. Administration of cycloheximide (10 mg/kg) by I.V. injection either before or during an infusion of Synacthen, inhibited steroidogenesis without affecting the vasodilator response.", "contents": "The sensitivity of adrenal responses to synthetic adrenocorticotrophin in the conscious unrestrained calf. 1. Changes in cortisol and corticosterone output and blood flow from the adrenal gland have been determined in the conscious unrestrained calf during I.V. infusions of synthetic adrenocorticotrophin (Synacthen) at 0-5 ng-kg(-1) min- minus 1 (low dose), 5 ng-kg- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1(very high dose). 2. Infusions at the low dose produced a rise in adrenal output of both cortisol and corticosterone to maximum values of approximately 100 and 30 ng-kg- minus 1 min- minus 1 respectively. Mean output of both steroids was significantly increased within 5 min, reached a maximum within 10 min and had fallen to resting levels 10 min after the infusion was discontinued. 3. The effects of infusions at both the high and very high doses were closely similar; maximal cortisol outputs were within the range 600-800 ng-kg- minus 1 min- minus 1 and corticosterone 350-500 ng-kg- minus 1 min- minus 1 in both groups. 4. When the infusions were terminated, pronounced differences were observed in the rates at which steroid outputs declined. Basal levels were restored within 10 min following the low dose and within 60 min in medium dose animals, but both cortisol and corticosterone output were still elevated 2 hr after infusion in high dose animals. In calves infused at the very high dose, cortisol output did not fall significantly during 2 hr period. The ratio of cortisol: corticosterone released from the adrenal gland immediately before infusion (3-2 +/- 0-3) approximated to the proportions in which the two steroids were found in the arterial plasma, but fell progressively to a minimum (1-3 +/- 0-1) with increasing doses of Synacthen. Conversely, the ratio of the steroids in the arterial plasma was increased during infusions at the low dose, but not at the higher doses. 6. No significant change in adrenal blood flow occurred during Synacthen infusion in low dose animals despite the increase in steroid output. In medium dose animals blood flow through the gland rose during infusion by approximately 75 per cent while in both high and very high dose animals the flow increased by up to 300 percent. 7. In the three groups in which adrenal hyperaemia occurred, blood flow had fallen to within the resting range 45 min after infusion: in each case this fall was much more rapid than the fall in steroid output. No significant increase in aortic blood pressure or heart rate accompanied infusion of Synacthen, indicating that adrenal hyperaemia was dependent upon vasodilatation with the gland. 8. Administration of cycloheximide (10 mg/kg) by I.V. injection either before or during an infusion of Synacthen, inhibited steroidogenesis without affecting the vasodilator response."} {"id": "PMID:167158", "title": "Two populations or granular vesicles in constricted post-ganglionic sympathetic nerves.", "content": "1. A comparative study has been made of the effects of different fixatives on the ultrastructural appearance of granular vesicles accumulated against a constriction in cat hypogastric nerves. 2. After fixation in either osmium tetroxide or in glutaraldehyde followed by post-osmication accumulations of large granular vesicles (65-90 nm in diameter) were observed in profiles of swollen axons. 3. Fixation in acrolein and sodium dichromate revealed a second population of small granular vesicles (mostly 30-50 nm in diameter) in addition to the large vesicles seen after the other fixatives. 4. In reserpinized cats the small granular vesicles were absent. The large granular vesicles were much less numerous, irrespective of the fixative used. 5. It is suggested that either the small vesicles occur in normal noradrenergic axons but are only revealed by catecholamine-sensitive fixatives or they occur as a result of constricting the nerve trunk. Evidence for and against these possibilities is discussed.", "contents": "Two populations or granular vesicles in constricted post-ganglionic sympathetic nerves. 1. A comparative study has been made of the effects of different fixatives on the ultrastructural appearance of granular vesicles accumulated against a constriction in cat hypogastric nerves. 2. After fixation in either osmium tetroxide or in glutaraldehyde followed by post-osmication accumulations of large granular vesicles (65-90 nm in diameter) were observed in profiles of swollen axons. 3. Fixation in acrolein and sodium dichromate revealed a second population of small granular vesicles (mostly 30-50 nm in diameter) in addition to the large vesicles seen after the other fixatives. 4. In reserpinized cats the small granular vesicles were absent. The large granular vesicles were much less numerous, irrespective of the fixative used. 5. It is suggested that either the small vesicles occur in normal noradrenergic axons but are only revealed by catecholamine-sensitive fixatives or they occur as a result of constricting the nerve trunk. Evidence for and against these possibilities is discussed."} {"id": "PMID:167161", "title": "Preservation of early discharge of muscle afferents in acrylamide neuropathy.", "content": "1. Responses to stretch and the 'early discharge' have been studied in acrylamide neuropathy in the expectation that functional block of the nerve terminals would allow these two processes to be dissociated. 2. Of 538 single group I and group II muscle afferents which were nonresponsive to stretch, ninety-nine displayed 'early discharge' which appeared to be identical with that described in normally functioning muscle stretch afferents. 3. Preservation of 'early discharge' in non-responsive fibres indicates these impulses do not arise from excitation of the muscle spindle itself. The evidence indicates that 'early discharge' is usually ephaptically excited by the muscle action potential.", "contents": "Preservation of early discharge of muscle afferents in acrylamide neuropathy. 1. Responses to stretch and the 'early discharge' have been studied in acrylamide neuropathy in the expectation that functional block of the nerve terminals would allow these two processes to be dissociated. 2. Of 538 single group I and group II muscle afferents which were nonresponsive to stretch, ninety-nine displayed 'early discharge' which appeared to be identical with that described in normally functioning muscle stretch afferents. 3. Preservation of 'early discharge' in non-responsive fibres indicates these impulses do not arise from excitation of the muscle spindle itself. The evidence indicates that 'early discharge' is usually ephaptically excited by the muscle action potential."} {"id": "PMID:167162", "title": "Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions.", "content": "1. In the intact organism, an increase in K+ concentration decreases the reactivity of blood vessels to sympathetic stimulation. The present experiments were designed to determine whether or not K+ interferes with adrenergic neurotransmission. 2. Helical strips cut from dogs' saphenous veins were incubated (4 hr) in Krebs-Ringer solution containing [7-3H]norepinephrine (5 times 10(-8) g/ml). The preparations were mounted for superfusion and isometric tension recording; the superfusate was collected for estimation of total radioactivity and for chromatographic separation of 3H-labelled norepinephrine and metabolites. 3. Supramaximal electric stimulation (5 Hz, 9 V, 2 msec) increased the tension and the [3H]norepinephrine efflux. Increasing the K+ concentration from 5-9 to 1, 15, and 20 m-equiv/l. caused a progressive depression of these contractions and diminished the total 3H efflux in proportion to the relaxation; the decrease in 3H efflux reflected a decrease in intact [3H]norepinephrine. The same increase in K+ concentration did not alter basal tension or basal 3H efflux. 4. Addition of tyramine (4 times 10(-6) g/ml. min) to the superfusate augmented both the tension and the efflux, but these actions were not depresesd by increasing the K+ concentration. 5. Cocaine, phentolamine, and phenoxybenzamine did not prevent the depression by K+ of the response to electric stimulation. 6. These experiments show that K+ causes relaxation of venous smooth muscle constricted by sympathetic stimulation and does so by inhibiting the release of norepinephrine from nerve endings. By contrast, K+ does not inhibit norepinephrine release in response to tyramine. 7. During submaximal electric stimulation (5 Hz, 1-8--3 V, 2 msec), increasing the K+ concentration from 5-9 to 10 and 15 m-equiv/l. potentiated the contractions and increased the [3H]norepinephrine efflux; at 20 m-equil/l, K+ caused transient increases in tension and 3H efflux followed by relaxation and decreased norepinephrine release. After addition of cocaine (10(-5) g/ml. min), K+ only caused relaxation and decrease in 3H efflux, showing that, in addition to inhibition of norepinephrine release, K+ also inhibits the reuptake process. 8. In higher concentrations (40 m-equil/l.), K+ caused both a liberation of norepinephrine and a direct activation of the smooth muscle cells.", "contents": "Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions. 1. In the intact organism, an increase in K+ concentration decreases the reactivity of blood vessels to sympathetic stimulation. The present experiments were designed to determine whether or not K+ interferes with adrenergic neurotransmission. 2. Helical strips cut from dogs' saphenous veins were incubated (4 hr) in Krebs-Ringer solution containing [7-3H]norepinephrine (5 times 10(-8) g/ml). The preparations were mounted for superfusion and isometric tension recording; the superfusate was collected for estimation of total radioactivity and for chromatographic separation of 3H-labelled norepinephrine and metabolites. 3. Supramaximal electric stimulation (5 Hz, 9 V, 2 msec) increased the tension and the [3H]norepinephrine efflux. Increasing the K+ concentration from 5-9 to 1, 15, and 20 m-equiv/l. caused a progressive depression of these contractions and diminished the total 3H efflux in proportion to the relaxation; the decrease in 3H efflux reflected a decrease in intact [3H]norepinephrine. The same increase in K+ concentration did not alter basal tension or basal 3H efflux. 4. Addition of tyramine (4 times 10(-6) g/ml. min) to the superfusate augmented both the tension and the efflux, but these actions were not depresesd by increasing the K+ concentration. 5. Cocaine, phentolamine, and phenoxybenzamine did not prevent the depression by K+ of the response to electric stimulation. 6. These experiments show that K+ causes relaxation of venous smooth muscle constricted by sympathetic stimulation and does so by inhibiting the release of norepinephrine from nerve endings. By contrast, K+ does not inhibit norepinephrine release in response to tyramine. 7. During submaximal electric stimulation (5 Hz, 1-8--3 V, 2 msec), increasing the K+ concentration from 5-9 to 10 and 15 m-equiv/l. potentiated the contractions and increased the [3H]norepinephrine efflux; at 20 m-equil/l, K+ caused transient increases in tension and 3H efflux followed by relaxation and decreased norepinephrine release. After addition of cocaine (10(-5) g/ml. min), K+ only caused relaxation and decrease in 3H efflux, showing that, in addition to inhibition of norepinephrine release, K+ also inhibits the reuptake process. 8. In higher concentrations (40 m-equil/l.), K+ caused both a liberation of norepinephrine and a direct activation of the smooth muscle cells."} {"id": "PMID:167169", "title": "The production of neuraminidase by food poisoning strains of Clostridium welchii (C. perfringens).", "content": "The production of neuraminidase by a classical strain of Clostridium welchii (C. perfringens) type A was studied. Good yields were produced in 5% Proteose Peptone-water medium (PPW5); the enzyme was essentially extracellular but some further neuraminidase could be released by ultrasonic disintegration of the cells. This also released N-acyl neuraminic acid-aldolase (NAN-aldolase) and the degree to which this interferes with the assay for neuraminidase was evaluated. Forty-one British reference food-poisoning strains of C. welchii type A were examined for extracellular neuraminidase production in PPW5. Twelve of 17 strains that produce so-called heat-sensitive spores were neuraminidase positive whereas 20 of 24 strains that are non-haemolytic and produce very heat-resistant sporeswere neuraminidase negative. Variation was found in the ability to produce neuraminidase among strains of a single Hobbs' serotype; four Hobbs' type-13 strains produced neuraminidase but a fifth did not. Disruption of the cells of a Hobbs' type-2 strain that did not produce any extracellular neuraminidase released NAN-aldolase but there was no evidence of cell-associated neuraminidase. British food-poisoning strains of C. welchii type A thus include some that are clearly neuraminidase positive and some that still cannot be shown to produce neuraminidase. There is no correlation between lack of neuraminidase production and the ability to cause food poisoning, although the majority of non-haemolytic heat-resistant strains do not produce neuraminidase. It remains possible that neuraminidase may play a part in C. welchii gas gangrene; it is suggested that the ability to define neuraminidase-negative strains may now be of value in investigating this possibility.", "contents": "The production of neuraminidase by food poisoning strains of Clostridium welchii (C. perfringens). The production of neuraminidase by a classical strain of Clostridium welchii (C. perfringens) type A was studied. Good yields were produced in 5% Proteose Peptone-water medium (PPW5); the enzyme was essentially extracellular but some further neuraminidase could be released by ultrasonic disintegration of the cells. This also released N-acyl neuraminic acid-aldolase (NAN-aldolase) and the degree to which this interferes with the assay for neuraminidase was evaluated. Forty-one British reference food-poisoning strains of C. welchii type A were examined for extracellular neuraminidase production in PPW5. Twelve of 17 strains that produce so-called heat-sensitive spores were neuraminidase positive whereas 20 of 24 strains that are non-haemolytic and produce very heat-resistant sporeswere neuraminidase negative. Variation was found in the ability to produce neuraminidase among strains of a single Hobbs' serotype; four Hobbs' type-13 strains produced neuraminidase but a fifth did not. Disruption of the cells of a Hobbs' type-2 strain that did not produce any extracellular neuraminidase released NAN-aldolase but there was no evidence of cell-associated neuraminidase. British food-poisoning strains of C. welchii type A thus include some that are clearly neuraminidase positive and some that still cannot be shown to produce neuraminidase. There is no correlation between lack of neuraminidase production and the ability to cause food poisoning, although the majority of non-haemolytic heat-resistant strains do not produce neuraminidase. It remains possible that neuraminidase may play a part in C. welchii gas gangrene; it is suggested that the ability to define neuraminidase-negative strains may now be of value in investigating this possibility."} {"id": "PMID:167170", "title": "Induction of mutation in Staphylococcus aureus by ethylmethane sulphonate.", "content": "Staphylococcus aureus strains were treated with ethylmethane sulphonate with the object of obtaining mutants that differed from the wild type in one of the properties that might contribute to virulence. Mutants with isolated loss or deficient production of gamma-haemolysin, coagulase, leucocidin and staphylokinase were obtained. Changes in more than one property were often observed. The loss of delta-lysin production was always coupled with an appreciable reduction in P-V leucocidin production. With that exception, systematised combined loss of a restricted number of staphylococcal characteristics was not observed. Mutants that had lost all characteristics of S. aureus were phage-resistant. Isolated loss of staphylokinase production and deficient P-V leucocidin production were found to be due to the independent loss of two prophages.", "contents": "Induction of mutation in Staphylococcus aureus by ethylmethane sulphonate. Staphylococcus aureus strains were treated with ethylmethane sulphonate with the object of obtaining mutants that differed from the wild type in one of the properties that might contribute to virulence. Mutants with isolated loss or deficient production of gamma-haemolysin, coagulase, leucocidin and staphylokinase were obtained. Changes in more than one property were often observed. The loss of delta-lysin production was always coupled with an appreciable reduction in P-V leucocidin production. With that exception, systematised combined loss of a restricted number of staphylococcal characteristics was not observed. Mutants that had lost all characteristics of S. aureus were phage-resistant. Isolated loss of staphylokinase production and deficient P-V leucocidin production were found to be due to the independent loss of two prophages."} {"id": "PMID:167172", "title": "The membrane action of antidiuretic hormone (ADH) on toad urinary bladder.", "content": "Radioactive tracer and electrical techniques were used to study the transport of nonelectrolytes and sodium, respectively, across toad urinary bladders in the presence and absence of ADH. The permeability of lipophilic molecules was roughly proportional to bulk phase oil/water partition coefficients both in the presence and absence of hormone; i.e., ADH elicited a general nonselective increase in the permeation of all nine solutes tested. The branched nonelectrolyte, isobutyramide, was less permeable than its straight-chain isomer, n-butyramide, in control tissues. ADH reduced the discrimination between these structural isomers. Hydrophilic solutes permeated more rapidly than expected. In the presence of hormone, there was no change in the permeation of large hydrophilic solutes considered to move via an extracellular pathway, but there was a marked increase in the permeability of water and other small hydrophilic solutes. Collectively, these results suggest that ADH acts to increase the motional freedom or fluidity of lipids in the cell membrane which is considered to be the preferred pathway for the permeation of lipophilic and small hydrophilic molecules. At concentrations of cAMP and ADH which elicit equivalent increments in the shortcircuit current, the effects of these agents on nonelectrolyte transport and membrane electrical conductance are divergent. Such observations suggest that some membrane effects of ADH may not be directly dependent upon cAMP. ADH in the mucosal solution increased the permeability of the toad bladder when the surface charge on the outer surface of the apical membrane was screened with the polyvalent cation, La-3+. These experiments emphasize that interaction of ADH with membranes of toad urinary bladder may account for at least some effects of this hormone.", "contents": "The membrane action of antidiuretic hormone (ADH) on toad urinary bladder. Radioactive tracer and electrical techniques were used to study the transport of nonelectrolytes and sodium, respectively, across toad urinary bladders in the presence and absence of ADH. The permeability of lipophilic molecules was roughly proportional to bulk phase oil/water partition coefficients both in the presence and absence of hormone; i.e., ADH elicited a general nonselective increase in the permeation of all nine solutes tested. The branched nonelectrolyte, isobutyramide, was less permeable than its straight-chain isomer, n-butyramide, in control tissues. ADH reduced the discrimination between these structural isomers. Hydrophilic solutes permeated more rapidly than expected. In the presence of hormone, there was no change in the permeation of large hydrophilic solutes considered to move via an extracellular pathway, but there was a marked increase in the permeability of water and other small hydrophilic solutes. Collectively, these results suggest that ADH acts to increase the motional freedom or fluidity of lipids in the cell membrane which is considered to be the preferred pathway for the permeation of lipophilic and small hydrophilic molecules. At concentrations of cAMP and ADH which elicit equivalent increments in the shortcircuit current, the effects of these agents on nonelectrolyte transport and membrane electrical conductance are divergent. Such observations suggest that some membrane effects of ADH may not be directly dependent upon cAMP. ADH in the mucosal solution increased the permeability of the toad bladder when the surface charge on the outer surface of the apical membrane was screened with the polyvalent cation, La-3+. These experiments emphasize that interaction of ADH with membranes of toad urinary bladder may account for at least some effects of this hormone."} {"id": "PMID:167182", "title": "Assay for Epstein-Barr virus based on stimulation of DNA synthesis in mixed leukocytes from human umbilical cord blood.", "content": "Relationships between the rate of DNA synthesis in cultured human umbilical cord leukocytes and the multiplicity of added Epstein-Barr virus (EBV) were studied. At low multiplicities of approximately 0.1 transforming units/cell (approximately 10 physical particles/cell), inoculated cultures demonstrated increased rates of DNA synthesis, by comparison to uninoculated cultures, 3 days after inoculation. Stimulation of DNA synthesis was evident of progressively longer intervals after inoculations of 10-fold dilutions of virus. The rate of DNA synthesis, determined by short [-3H]thymidine pulses, reflected as small as twofold changes in multiplicity and thus can serve as a quantitative assay for the virus. Changes in the rate of DNA synthesis were evident before increases in cell number or alteration in morphology. Stimulation of DNA synthesis in umbilical cord leukocytes was inhibited by treatment of EBV with antibody and also in graded fashion, by progressive doses of UV irradiation to the virus. Induction of DNA synthesis by EBV was serum dependent. Estimates of the number of cells transformed were obtained by extrapolation from a standard curve relating known numbers of transformed cells to [-3H]thymidine incorporation and also by cloning cells after exposure to virus. At the low multiplicities of infection used in these experiments approximately 0.04 to 0.002 of the total cellular population was transformed. The high efficiency of cell transformation by EBV by comparison to other DNA tumor viruses is emphasized.", "contents": "Assay for Epstein-Barr virus based on stimulation of DNA synthesis in mixed leukocytes from human umbilical cord blood. Relationships between the rate of DNA synthesis in cultured human umbilical cord leukocytes and the multiplicity of added Epstein-Barr virus (EBV) were studied. At low multiplicities of approximately 0.1 transforming units/cell (approximately 10 physical particles/cell), inoculated cultures demonstrated increased rates of DNA synthesis, by comparison to uninoculated cultures, 3 days after inoculation. Stimulation of DNA synthesis was evident of progressively longer intervals after inoculations of 10-fold dilutions of virus. The rate of DNA synthesis, determined by short [-3H]thymidine pulses, reflected as small as twofold changes in multiplicity and thus can serve as a quantitative assay for the virus. Changes in the rate of DNA synthesis were evident before increases in cell number or alteration in morphology. Stimulation of DNA synthesis in umbilical cord leukocytes was inhibited by treatment of EBV with antibody and also in graded fashion, by progressive doses of UV irradiation to the virus. Induction of DNA synthesis by EBV was serum dependent. Estimates of the number of cells transformed were obtained by extrapolation from a standard curve relating known numbers of transformed cells to [-3H]thymidine incorporation and also by cloning cells after exposure to virus. At the low multiplicities of infection used in these experiments approximately 0.04 to 0.002 of the total cellular population was transformed. The high efficiency of cell transformation by EBV by comparison to other DNA tumor viruses is emphasized."} {"id": "PMID:167183", "title": "Evidence for the existence of protomers in the assembly of encephalomyocarditis virus.", "content": "Two capsid precursor subunits, which sediment on glycerol gradients at 13S and 14S, respectively, have been identified in cytoplasmic extracts of encephalomyocarditis virus-infected HeLa cells. The 13S subunit, which was detected after a 10-min pulse label with -3H-labeled amino acids, contained only capsid precursor chain A (mol wt 100,000). When the 10-min pulse label in such cells was chased for 20 min, the A-containing 13S subunit in the cytoplasmic extracts was replaced by a 14S subunit containing equimolar proportions of three chains: epsilon, gamma, and alpha. This (epsilon, gamma, alpha)-containing 14S subunit could be dissociated into 6S subunits with the same polypeptide composition. The sedimentation properties and the polypeptide stoichiometry of these three precursor subunits, when compared with those of the 13S, (beta, gamma, alpha)(5), and 5S, (beta, gamma, alpha), subunits derived by acid dissociation of purified virions, suggest the following structural assignments: 13S, (A)(5); 14S, (epsilon, gamma, alpha)(5), 6S, (epsilon, gamma, alpha). The molecular weights of the individually isolated capsid chains were determined by gel filtration in 6 M guanidine hydrochloride to be: epsilon, 36,000; alpha, 32,000; beta, 29,500; gamma, 26,500; and delta, 7,800. With the exception of the delta-chain, these values are in reasonable agreement with the values previously determined by electrophoresis on sodium dodecyl sulfatepolyacrylamide gels. These data support the hypothesis that picornavirus capsids are assembled from identical protomers according to the following scheme: (A) leads to (A)(5) leads to (epsilon, gamma, alpha)(5) leads to (delta, beta, gamma, alpha)60-n(epsilon, gamma, alpha)n where n is the number of immature protomers per virion.", "contents": "Evidence for the existence of protomers in the assembly of encephalomyocarditis virus. Two capsid precursor subunits, which sediment on glycerol gradients at 13S and 14S, respectively, have been identified in cytoplasmic extracts of encephalomyocarditis virus-infected HeLa cells. The 13S subunit, which was detected after a 10-min pulse label with -3H-labeled amino acids, contained only capsid precursor chain A (mol wt 100,000). When the 10-min pulse label in such cells was chased for 20 min, the A-containing 13S subunit in the cytoplasmic extracts was replaced by a 14S subunit containing equimolar proportions of three chains: epsilon, gamma, and alpha. This (epsilon, gamma, alpha)-containing 14S subunit could be dissociated into 6S subunits with the same polypeptide composition. The sedimentation properties and the polypeptide stoichiometry of these three precursor subunits, when compared with those of the 13S, (beta, gamma, alpha)(5), and 5S, (beta, gamma, alpha), subunits derived by acid dissociation of purified virions, suggest the following structural assignments: 13S, (A)(5); 14S, (epsilon, gamma, alpha)(5), 6S, (epsilon, gamma, alpha). The molecular weights of the individually isolated capsid chains were determined by gel filtration in 6 M guanidine hydrochloride to be: epsilon, 36,000; alpha, 32,000; beta, 29,500; gamma, 26,500; and delta, 7,800. With the exception of the delta-chain, these values are in reasonable agreement with the values previously determined by electrophoresis on sodium dodecyl sulfatepolyacrylamide gels. These data support the hypothesis that picornavirus capsids are assembled from identical protomers according to the following scheme: (A) leads to (A)(5) leads to (epsilon, gamma, alpha)(5) leads to (delta, beta, gamma, alpha)60-n(epsilon, gamma, alpha)n where n is the number of immature protomers per virion."} {"id": "PMID:167184", "title": "Structural polypeptides of rabbit, bovine, and human papillomaviruses.", "content": "The number and apparent molecular weight of the structural polypeptides of Shope rabbit papilloma virus (RPV), bovine papilloma virus (BPV), and human papilloma virus (HPV) were estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Up to 10 polypeptides were detected in highly purified BPV and HPV full particles; a close homology was found between the polypeptide composition of both viruses. Purified RPV virions gave a similar polypeptide pattern. The main components of the three papillomaviruses are the major polypeptide (VP1) with a mol wt of approximately 54,000 and the three smaller polypeptides (VP8, 9, 10) with mol wt of about 16,500, 15,500 and 12,500, respectively. VP8, VP9, and VP10 are never detected in empty capsids. When BPV virions were disrupted with alkaline buffer, the six lower-molecular-weight polypeptides (VP5 to 10) remained associated with viral DNA. This suggests that they are internal components of the virions and that the four higher-molecular-weight polypeptides (VP1 to 4) may represent external components. The polypeptide compositions of BPV and polyoma virus, another papovavirus, have been compared. The number of BPV and polyoma virus components (10 and 6, respectively) and the molecular weight of their major polypeptide (54,000 and 44,500, respectively) are different; however, the three main DNA-associated polypeptides of BPV (VP8, 9, 10) and the three histone-like components of polyoma virus (VP4, 5, 6) were shown to have identical apparent molecular weights. The possibility that some of the minor components of papillomaviruses may be proteolytic degradation products or cell protein contaiminants is discussed.", "contents": "Structural polypeptides of rabbit, bovine, and human papillomaviruses. The number and apparent molecular weight of the structural polypeptides of Shope rabbit papilloma virus (RPV), bovine papilloma virus (BPV), and human papilloma virus (HPV) were estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Up to 10 polypeptides were detected in highly purified BPV and HPV full particles; a close homology was found between the polypeptide composition of both viruses. Purified RPV virions gave a similar polypeptide pattern. The main components of the three papillomaviruses are the major polypeptide (VP1) with a mol wt of approximately 54,000 and the three smaller polypeptides (VP8, 9, 10) with mol wt of about 16,500, 15,500 and 12,500, respectively. VP8, VP9, and VP10 are never detected in empty capsids. When BPV virions were disrupted with alkaline buffer, the six lower-molecular-weight polypeptides (VP5 to 10) remained associated with viral DNA. This suggests that they are internal components of the virions and that the four higher-molecular-weight polypeptides (VP1 to 4) may represent external components. The polypeptide compositions of BPV and polyoma virus, another papovavirus, have been compared. The number of BPV and polyoma virus components (10 and 6, respectively) and the molecular weight of their major polypeptide (54,000 and 44,500, respectively) are different; however, the three main DNA-associated polypeptides of BPV (VP8, 9, 10) and the three histone-like components of polyoma virus (VP4, 5, 6) were shown to have identical apparent molecular weights. The possibility that some of the minor components of papillomaviruses may be proteolytic degradation products or cell protein contaiminants is discussed."} {"id": "PMID:167185", "title": "Post-transcriptional restriction of human adenovirus expression in monkey cells.", "content": "Infection of the continuous simian cell lines CV-1 and BSC-1 with human adenovirus type 2 (Ad2) is abortive. However, the restriction of Ad2 reproduction in these cells can be overcome by increasing the Ad2 infectious dose or by coinfection with simian virus 40. Vero, another established simian cell line free of detectable endogenous simian virus 40 DNA, is not restricted in its ability to promote Ad2 growth even at low input multiplicities of Ad2 and in the absence of SV40 helper. The amount of structural Ad2 proteins in total cell extracts of enhanced BSC-1 cells is at least two orders of magnitude higher than that of unenhanced cells. In contrast, comparable quantities of Ad2 mRNA specifying these proteins are found in both the enhanced and the unenhanced cell. Both sets of mRNA can be translated in a cell-free system with equal efficiency.", "contents": "Post-transcriptional restriction of human adenovirus expression in monkey cells. Infection of the continuous simian cell lines CV-1 and BSC-1 with human adenovirus type 2 (Ad2) is abortive. However, the restriction of Ad2 reproduction in these cells can be overcome by increasing the Ad2 infectious dose or by coinfection with simian virus 40. Vero, another established simian cell line free of detectable endogenous simian virus 40 DNA, is not restricted in its ability to promote Ad2 growth even at low input multiplicities of Ad2 and in the absence of SV40 helper. The amount of structural Ad2 proteins in total cell extracts of enhanced BSC-1 cells is at least two orders of magnitude higher than that of unenhanced cells. In contrast, comparable quantities of Ad2 mRNA specifying these proteins are found in both the enhanced and the unenhanced cell. Both sets of mRNA can be translated in a cell-free system with equal efficiency."} {"id": "PMID:167186", "title": "Selective inhibition of herpes simplex virus by 5-amino-2,5-dideoxy-5-iodouridine.", "content": "5-Amino-2,5-dideoxy-5-iodouridine, a nel thymidine analogue, is a potent inhibitor of herpes simplex virus type 1 replication. In contrast to most other nucleoside analogues which possess antiviral activity, 5-amino-2,5-dideoxy-5-iodouridine exhibits little, if any, cellular toxicity. Preliminary evidence suggests that 5-amino-2,5-dideoxy-5-iodouridine selectively inhibits viral-specific DNA synthesis.", "contents": "Selective inhibition of herpes simplex virus by 5-amino-2,5-dideoxy-5-iodouridine. 5-Amino-2,5-dideoxy-5-iodouridine, a nel thymidine analogue, is a potent inhibitor of herpes simplex virus type 1 replication. In contrast to most other nucleoside analogues which possess antiviral activity, 5-amino-2,5-dideoxy-5-iodouridine exhibits little, if any, cellular toxicity. Preliminary evidence suggests that 5-amino-2,5-dideoxy-5-iodouridine selectively inhibits viral-specific DNA synthesis."} {"id": "PMID:167187", "title": "Temperature-sensitive mutants of simian virus 40 selected by transforming ability.", "content": "Eight temperature-sensitive mutants of simian virus 40 which transform rat cells at 32.5 C but not at 38.5 C have been isolated. All the mutants were also temperature sensitive for replication in African green monkey kidney cells and five of them were classified into a single complementation group. No mutant incapable of transforming rat cells at either temperature was isolated.", "contents": "Temperature-sensitive mutants of simian virus 40 selected by transforming ability. Eight temperature-sensitive mutants of simian virus 40 which transform rat cells at 32.5 C but not at 38.5 C have been isolated. All the mutants were also temperature sensitive for replication in African green monkey kidney cells and five of them were classified into a single complementation group. No mutant incapable of transforming rat cells at either temperature was isolated."} {"id": "PMID:167188", "title": "Characterization of T antigen in cells infected with a temperature-sensitive mutant of simian virus 40.", "content": "T antigen induced in African green monkey kidney cells by a temperature-sensitive mutant of simian virus 40, defective in a function required for cell transformation, was characterized. The number of T antigen-positive cells estimated by an immunofluorescent techniques was almost equal at permissive (32.5 C) and restrictive (38.5 C) temperatures, but was slightly reduced when the infected cells were incubated at a higher temperature (40.5 C). However, a complement fixation test indicated that the amount of T antigen induced by the mutant is not significantly different from that induced by wild-type virus at 40.5 C. These results suggest that the T antigen-inducing ability of the mutant is not defective. Two distinct molecular species of T antigen were induced by the mutant at the permissive temperature, whereas only one form was observed at the restrictive temperature. The larger molecular form (14 to 15S) induced by the mutant at the permissive temperature was more heat labile than that induced by wild-type virus, suggesting that the mutated gene product is a component of the larger molecular form.", "contents": "Characterization of T antigen in cells infected with a temperature-sensitive mutant of simian virus 40. T antigen induced in African green monkey kidney cells by a temperature-sensitive mutant of simian virus 40, defective in a function required for cell transformation, was characterized. The number of T antigen-positive cells estimated by an immunofluorescent techniques was almost equal at permissive (32.5 C) and restrictive (38.5 C) temperatures, but was slightly reduced when the infected cells were incubated at a higher temperature (40.5 C). However, a complement fixation test indicated that the amount of T antigen induced by the mutant is not significantly different from that induced by wild-type virus at 40.5 C. These results suggest that the T antigen-inducing ability of the mutant is not defective. Two distinct molecular species of T antigen were induced by the mutant at the permissive temperature, whereas only one form was observed at the restrictive temperature. The larger molecular form (14 to 15S) induced by the mutant at the permissive temperature was more heat labile than that induced by wild-type virus, suggesting that the mutated gene product is a component of the larger molecular form."} {"id": "PMID:167189", "title": "Both NS and L proteins are required for in vitro RNA synthesis by vesicular stomatitis virus.", "content": "Vesicular stomatitis virions, Indiana serotype, were solubilized with high salt solubilizer and separated by ultracentrifugation into a supernatant fraction containing L, G, NS, and M proteins and pellet fraction containing the RNA complexed with N protein. NS protein was purified from the supernatnat fluid by sequential chromatography on phosphocellulose and diethylaminoethyl cellulose columns. The purified NS protein was assayed in a standard transcription system in combination with purified L protein and purified template (pellet fraction) prepared by renografin or CsCl banding. Results of the polymerase assays indicate that both L and NS proteins are required to reconstitute transcription activity with a highly purified template composed of only RNA and N protein. The NS protein polymerase activity is destroyed by trypsin but withstands 90 C temperatures for 10 min. Cytoplasmic NS protein can substitute for virion NS protein in the in vitro transcription assay.", "contents": "Both NS and L proteins are required for in vitro RNA synthesis by vesicular stomatitis virus. Vesicular stomatitis virions, Indiana serotype, were solubilized with high salt solubilizer and separated by ultracentrifugation into a supernatant fraction containing L, G, NS, and M proteins and pellet fraction containing the RNA complexed with N protein. NS protein was purified from the supernatnat fluid by sequential chromatography on phosphocellulose and diethylaminoethyl cellulose columns. The purified NS protein was assayed in a standard transcription system in combination with purified L protein and purified template (pellet fraction) prepared by renografin or CsCl banding. Results of the polymerase assays indicate that both L and NS proteins are required to reconstitute transcription activity with a highly purified template composed of only RNA and N protein. The NS protein polymerase activity is destroyed by trypsin but withstands 90 C temperatures for 10 min. Cytoplasmic NS protein can substitute for virion NS protein in the in vitro transcription assay."} {"id": "PMID:167190", "title": "Recombination between endogenous and exogenous RNA tumor virus genes as analyzed by nucleic acid hybridization.", "content": "Certain chicken cells that do not spontaneously release virus particles have been shown to produce a subgroup E avian RNA tumor virus, Rous-associated virus 60 (RAV-60), after infection with viruses of other subgroups. The nucleic acids of RAV-60 were analyzed for sequence homologies with the viral nucleic acids contained in the uninfected cell and with those of RAV-2, the exogenous virus used for the preparation of this particular RAV-60 isolate. In addition, these nucleic acids were compared with those of RAV-0, an endogenous virus spontaneously released from line 100 chicken cells. RAV-60 appears to be intermediate between RAV-0 and RAV-2 in its genetic composition, based on the pattern of hybridization obtained with the nucleic acids of these viruses and on the melting profiles of the various hybrid combinations. Of the three viruses tested, RAV-0 appears to have the greatest sequence homology with the viral nucleic acids of the uninfected cell. Hybridization between RAV-60 3-H-labeled complementary DNA and either DNA or RNA from the uninfected cell indicates that RAV-60 contains some nucleic acid sequences which are not present in the cell. In addition, some RAV-60 sequences which hybridize with the cell nucleic acid contain significant amounts of mismatching, as indicated by the lower thermal stability of these hybrid duplexes. Hybrid formation between these partially homologous sequences was excluded under stringent annealing conditions. The data indicate that RAV-60 is a recombinant between exogenous and endogenous viral genes.", "contents": "Recombination between endogenous and exogenous RNA tumor virus genes as analyzed by nucleic acid hybridization. Certain chicken cells that do not spontaneously release virus particles have been shown to produce a subgroup E avian RNA tumor virus, Rous-associated virus 60 (RAV-60), after infection with viruses of other subgroups. The nucleic acids of RAV-60 were analyzed for sequence homologies with the viral nucleic acids contained in the uninfected cell and with those of RAV-2, the exogenous virus used for the preparation of this particular RAV-60 isolate. In addition, these nucleic acids were compared with those of RAV-0, an endogenous virus spontaneously released from line 100 chicken cells. RAV-60 appears to be intermediate between RAV-0 and RAV-2 in its genetic composition, based on the pattern of hybridization obtained with the nucleic acids of these viruses and on the melting profiles of the various hybrid combinations. Of the three viruses tested, RAV-0 appears to have the greatest sequence homology with the viral nucleic acids of the uninfected cell. Hybridization between RAV-60 3-H-labeled complementary DNA and either DNA or RNA from the uninfected cell indicates that RAV-60 contains some nucleic acid sequences which are not present in the cell. In addition, some RAV-60 sequences which hybridize with the cell nucleic acid contain significant amounts of mismatching, as indicated by the lower thermal stability of these hybrid duplexes. Hybrid formation between these partially homologous sequences was excluded under stringent annealing conditions. The data indicate that RAV-60 is a recombinant between exogenous and endogenous viral genes."} {"id": "PMID:167191", "title": "Nucleic acid homology of murine xenotropic type C viruses.", "content": "Two major subclasses of xenotropic (X-tropic) murine type C viruses can be distinguished by nucleic acid hybridization. The most frequently encountered subclass (MuLV-X-alpha) includes isolates from BALB/c, C57BL/6J, C58/J, AKR/J, CBA/J, and DBA/2J inbred strains and from the Asian feral mouse subspecies Mus musculus molossinus. The other subclass (MuLV-X-beta) consists of viruses isolated from the NIH Swiss and NZB/BINJ strains. Thus, significant polymorphism exists among the endogenous type C virogenes of a single species, Mus musculus. MuLV-X-alpha genes are found in strains that also have endogenous mouse-tropic viruses (either N-tropic, B-tropic, or both), whereas the MuLV-X-beta subclass is restricted to mouse strains from which mouse-tropic viruses have not yet been isolated. The results are consistent with a model which proposes that mouse-tropic endogenous viruses are derived from the MuLV-X-alpha subclass.", "contents": "Nucleic acid homology of murine xenotropic type C viruses. Two major subclasses of xenotropic (X-tropic) murine type C viruses can be distinguished by nucleic acid hybridization. The most frequently encountered subclass (MuLV-X-alpha) includes isolates from BALB/c, C57BL/6J, C58/J, AKR/J, CBA/J, and DBA/2J inbred strains and from the Asian feral mouse subspecies Mus musculus molossinus. The other subclass (MuLV-X-beta) consists of viruses isolated from the NIH Swiss and NZB/BINJ strains. Thus, significant polymorphism exists among the endogenous type C virogenes of a single species, Mus musculus. MuLV-X-alpha genes are found in strains that also have endogenous mouse-tropic viruses (either N-tropic, B-tropic, or both), whereas the MuLV-X-beta subclass is restricted to mouse strains from which mouse-tropic viruses have not yet been isolated. The results are consistent with a model which proposes that mouse-tropic endogenous viruses are derived from the MuLV-X-alpha subclass."} {"id": "PMID:167192", "title": "DNA synthesis in polyoma virus infection. III. Mechanism of inhibition of viral DNA replication by cycloheximide.", "content": "The formation of viral DNA was inhibited in polyoma virus-infected cells in which protein synthesis had been blocked by cycloheximide. The present studies show the following. (i) The pool of replicating viral DNA molecules was reduced in cycloheximide-treated cells by an amount consistent with inhibition of [3-H]thymidine incorporation into viral DNA, whereas the rate of turnover of the replicating population was not affected. (ii) The rate of conversion of replicating molecules into closed-circular DNA was not affected by cycloheximide. (iii) The rate of elongation of nascent viral DNA fragments into strands of unit genome length was unaffected by cycloheximide. It is concluded that viral DNA synthesis is inhibited in the absence of protein synthesis exclusively at the level of initiation of new rounds of genome replication. Replicating molecules already initiated at the time of addition of cycloheximide matured into progeny closed-circular DNA at a normal rate.", "contents": "DNA synthesis in polyoma virus infection. III. Mechanism of inhibition of viral DNA replication by cycloheximide. The formation of viral DNA was inhibited in polyoma virus-infected cells in which protein synthesis had been blocked by cycloheximide. The present studies show the following. (i) The pool of replicating viral DNA molecules was reduced in cycloheximide-treated cells by an amount consistent with inhibition of [3-H]thymidine incorporation into viral DNA, whereas the rate of turnover of the replicating population was not affected. (ii) The rate of conversion of replicating molecules into closed-circular DNA was not affected by cycloheximide. (iii) The rate of elongation of nascent viral DNA fragments into strands of unit genome length was unaffected by cycloheximide. It is concluded that viral DNA synthesis is inhibited in the absence of protein synthesis exclusively at the level of initiation of new rounds of genome replication. Replicating molecules already initiated at the time of addition of cycloheximide matured into progeny closed-circular DNA at a normal rate."} {"id": "PMID:167193", "title": "Polyadenylic acid on poliovirus RNA. II. poly(A) on intracellular RNAs.", "content": "The content, size, and mechanism of synthesis of 3'-terminal poly(A) on the various intracellular species of poliovirus RNA have been examined. All viral RNA species bound to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. At 3 h after infection, the poly(A) on virion RNA, relicative intermediate RNA, polyribosomal RNA, and total cytoplasmic 35S RNA was heterogeneous in size with an average length of 75 nucleotides. By 6 h after infection many of the intracellular RNA's had poly(A) of over 150 nucleotides in length, but the poly(A) in virion RNA did not increase in size suggesting that the amount of poly(A) which can be encapsidated is limited. At all times, the double-stranded poliovirus RNA molecules had poly(A) of 150 to 200 nucleotides. Investigation of the kinetics of poly(A) appearance in the replicative intermediate and in finished 35S molecules indicated that poly(A) is the last portion of the 35S RNA to be synthesized; no nascent poly(A) could be detected in the replicative intermediate. Although this result indicates that poliovirus RNA is synthesized 5' leads to 3' like other RNA's, it also suggests that much of the poly(A) found in the replicative intermediate is an artifact possibly arising from the binding of finished 35S RNA molecules to the replicative intermediate during extraction. The addition of poly(A) to 35S RNA molecules was not sensitive to guanidene.", "contents": "Polyadenylic acid on poliovirus RNA. II. poly(A) on intracellular RNAs. The content, size, and mechanism of synthesis of 3'-terminal poly(A) on the various intracellular species of poliovirus RNA have been examined. All viral RNA species bound to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. At 3 h after infection, the poly(A) on virion RNA, relicative intermediate RNA, polyribosomal RNA, and total cytoplasmic 35S RNA was heterogeneous in size with an average length of 75 nucleotides. By 6 h after infection many of the intracellular RNA's had poly(A) of over 150 nucleotides in length, but the poly(A) in virion RNA did not increase in size suggesting that the amount of poly(A) which can be encapsidated is limited. At all times, the double-stranded poliovirus RNA molecules had poly(A) of 150 to 200 nucleotides. Investigation of the kinetics of poly(A) appearance in the replicative intermediate and in finished 35S molecules indicated that poly(A) is the last portion of the 35S RNA to be synthesized; no nascent poly(A) could be detected in the replicative intermediate. Although this result indicates that poliovirus RNA is synthesized 5' leads to 3' like other RNA's, it also suggests that much of the poly(A) found in the replicative intermediate is an artifact possibly arising from the binding of finished 35S RNA molecules to the replicative intermediate during extraction. The addition of poly(A) to 35S RNA molecules was not sensitive to guanidene."} {"id": "PMID:167194", "title": "Polyadenylic acid on poliovirus RNA. III. In vitro addition of polyadenylic acid to poliovirus RNAs.", "content": "A crude RNA polymerase preparation was made from HeLa cells infected for 3 h with poliovirus. All virus-specific RNA species labeled in vitro (35S RNA, replicative intermediate RNA [RI], and double-stranded RNA [dsRNA]) would bind to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. After incubation for 45 min with [3-H]ATP in the presence of the other three nucleoside triphosphates, the labeled poly(A) on the RI and dsRNA migrated on gels as relatively homogenous peaks approximately 200 nucleotides in length. In contrast, the poly(A) from the 35S RNA had a heterogeneous size distribution ranging from 50 to 250 nucleotides. In the absence of UTP, CTP, and GTP, the size of the newly labeled poly(A) on the dsRNA and RI RNA was the same as it was in the presence of all four nucleoside triphosphates. However the poly(A) on the 35S RNA lacked the larger sequences seen when the other three nucleoside triphosphates were present. When [3-H]ATP was used as the label in infected and uninfected extracts, heterogeneous single-stranded RNA sedimenting at less than 28S was also labeled. This heterogeneous RNA probably represents HeLa cytoplasmic RNA to which small lengths of poly(A) (approximately 15 nucleotides) had been added. These results indicate that in the in vitro system poly(A) can be added to both newly synthesized and preexisting RNA molecules. Furthermore, an enzyme capable of terminal addition of poly(A) exists in both infected and uninfected extracts.", "contents": "Polyadenylic acid on poliovirus RNA. III. In vitro addition of polyadenylic acid to poliovirus RNAs. A crude RNA polymerase preparation was made from HeLa cells infected for 3 h with poliovirus. All virus-specific RNA species labeled in vitro (35S RNA, replicative intermediate RNA [RI], and double-stranded RNA [dsRNA]) would bind to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. After incubation for 45 min with [3-H]ATP in the presence of the other three nucleoside triphosphates, the labeled poly(A) on the RI and dsRNA migrated on gels as relatively homogenous peaks approximately 200 nucleotides in length. In contrast, the poly(A) from the 35S RNA had a heterogeneous size distribution ranging from 50 to 250 nucleotides. In the absence of UTP, CTP, and GTP, the size of the newly labeled poly(A) on the dsRNA and RI RNA was the same as it was in the presence of all four nucleoside triphosphates. However the poly(A) on the 35S RNA lacked the larger sequences seen when the other three nucleoside triphosphates were present. When [3-H]ATP was used as the label in infected and uninfected extracts, heterogeneous single-stranded RNA sedimenting at less than 28S was also labeled. This heterogeneous RNA probably represents HeLa cytoplasmic RNA to which small lengths of poly(A) (approximately 15 nucleotides) had been added. These results indicate that in the in vitro system poly(A) can be added to both newly synthesized and preexisting RNA molecules. Furthermore, an enzyme capable of terminal addition of poly(A) exists in both infected and uninfected extracts."} {"id": "PMID:167195", "title": "Presence of herpes simplex virus-related antigens in transformed L cells.", "content": "Antiserum prepared against herpes simplex virus type 1 (HSV-1)-infected L cells, i.e., lytic antiserum, was shown by an indirect immunofluorescence test to stain 90 percent of HSV-transformed L or HeLa cells. Immunofluorescence in these cells was always most intense in the perinuclear cytoplasmic region. Similar results were obtained with antiserum prepared against HSV-transformed L cells. These data indicate that HSV-transformed cells (both L and HeLa) express HSV-related antigens. Antiserum prepared against HSV-1-transformed L cells, i.e., transformed-cell antiserum, was found to agglutinate purified HSV type 1 virions but failed to neutralize infectivity. This suggests that HSV-1 structural antigens are expressed in HSV-1-transformed L cells. Immunodiffusion studies showed that at least two HSV-related antigens could be demonstrated with antigens from HSV-1-transformed L cells and transformed-cell antiserum. These two antigens were shown to be present in all clonal lines of HSV-1-transformed cells examined, six L cell lines and one HeLa cell line. Therefore, we conclude that transformation of cells by HSV-1, which is known to be associated with acquisition of viral thymidine kinase, must also be associated with the presence of these two antigens. We performed experiments showing that there are species of HSV-related antibody in HSV-transformed cell antiserum that could not be absorbed out with antigens from HSV-infected L cells. Antibodies present in lytic antiserum were completely removed by antigen preparations from cells lytically infected with HSV-1. Also, lytic antiserum failed to block HSV-related staining of transformed L cells in a direct immunofluorescence test. These results are compatible with one of two notions: either (i) certain genes are expressed during transformation that are not expressed during lytic infection, or (ii) these genes are expressed to a much more reduced extent during lytic infection than in transformed cells.", "contents": "Presence of herpes simplex virus-related antigens in transformed L cells. Antiserum prepared against herpes simplex virus type 1 (HSV-1)-infected L cells, i.e., lytic antiserum, was shown by an indirect immunofluorescence test to stain 90 percent of HSV-transformed L or HeLa cells. Immunofluorescence in these cells was always most intense in the perinuclear cytoplasmic region. Similar results were obtained with antiserum prepared against HSV-transformed L cells. These data indicate that HSV-transformed cells (both L and HeLa) express HSV-related antigens. Antiserum prepared against HSV-1-transformed L cells, i.e., transformed-cell antiserum, was found to agglutinate purified HSV type 1 virions but failed to neutralize infectivity. This suggests that HSV-1 structural antigens are expressed in HSV-1-transformed L cells. Immunodiffusion studies showed that at least two HSV-related antigens could be demonstrated with antigens from HSV-1-transformed L cells and transformed-cell antiserum. These two antigens were shown to be present in all clonal lines of HSV-1-transformed cells examined, six L cell lines and one HeLa cell line. Therefore, we conclude that transformation of cells by HSV-1, which is known to be associated with acquisition of viral thymidine kinase, must also be associated with the presence of these two antigens. We performed experiments showing that there are species of HSV-related antibody in HSV-transformed cell antiserum that could not be absorbed out with antigens from HSV-infected L cells. Antibodies present in lytic antiserum were completely removed by antigen preparations from cells lytically infected with HSV-1. Also, lytic antiserum failed to block HSV-related staining of transformed L cells in a direct immunofluorescence test. These results are compatible with one of two notions: either (i) certain genes are expressed during transformation that are not expressed during lytic infection, or (ii) these genes are expressed to a much more reduced extent during lytic infection than in transformed cells."} {"id": "PMID:167196", "title": "Anatomy of herpes simplex virus DNA. II. Size, composition, and arrangement of inverted terminal repetitions.", "content": "Electron microscope studies on self-annealed intact single strands and on partially denatured molecules show that herpes simplex virus 1 DNA consists of two unequal regions, each bounded by inverted redundant sequences. Thus the region L (70 percent of the contour length of the DNA) separates the left terminal region a1b from its inverted repeat b'a'1, each of which comprises 6 percent of the DNA. The region S (9.4 percent of DNA) separates the right terminal region cas (4.3 percent of the DNA) from its inverted repeat a'sc'. The regions of the two termini which are inverted and repeated itnernally differ in topology. Thus, cas is guanine plus cytosine rich, whereas only the terminal 1 percent of the a1b region, designated as subregion a1, is guanine plus cytosine rich.", "contents": "Anatomy of herpes simplex virus DNA. II. Size, composition, and arrangement of inverted terminal repetitions. Electron microscope studies on self-annealed intact single strands and on partially denatured molecules show that herpes simplex virus 1 DNA consists of two unequal regions, each bounded by inverted redundant sequences. Thus the region L (70 percent of the contour length of the DNA) separates the left terminal region a1b from its inverted repeat b'a'1, each of which comprises 6 percent of the DNA. The region S (9.4 percent of DNA) separates the right terminal region cas (4.3 percent of the DNA) from its inverted repeat a'sc'. The regions of the two termini which are inverted and repeated itnernally differ in topology. Thus, cas is guanine plus cytosine rich, whereas only the terminal 1 percent of the a1b region, designated as subregion a1, is guanine plus cytosine rich."} {"id": "PMID:167197", "title": "Effect of DNA-negative and maturation-defective conditions on accumulation of functional messengers for T4 bacteriophage-specific dihydrofolate reductase and deoxynucleoside monophosphate kinase.", "content": "Messengers for T4 phage-specific deoxynucleoside monophosphate kinase overaccumulated in nonpermissive hosts infected with amber-defective viruses that displayed either the DNA-negative or maturation-defective phenotype. Under both conditions, however, transcription of functional messengers for dihydrofolate reductase followed essentially normal kinetics.", "contents": "Effect of DNA-negative and maturation-defective conditions on accumulation of functional messengers for T4 bacteriophage-specific dihydrofolate reductase and deoxynucleoside monophosphate kinase. Messengers for T4 phage-specific deoxynucleoside monophosphate kinase overaccumulated in nonpermissive hosts infected with amber-defective viruses that displayed either the DNA-negative or maturation-defective phenotype. Under both conditions, however, transcription of functional messengers for dihydrofolate reductase followed essentially normal kinetics."} {"id": "PMID:167198", "title": "Experience with the thoraco-abdominal incision for nephroblastoma in children less than 3 years old.", "content": "Our results with the routine use of a modified thoraco-abdominal incision in the treatment of patients with nephroblastoma are reported herein. We have used this incision successfully in 5 patients less than 3 years old and are impressed with the improved exposure. In our limited experience the thoracic extension has not adversely altered the operative or postoperative course.", "contents": "Experience with the thoraco-abdominal incision for nephroblastoma in children less than 3 years old. Our results with the routine use of a modified thoraco-abdominal incision in the treatment of patients with nephroblastoma are reported herein. We have used this incision successfully in 5 patients less than 3 years old and are impressed with the improved exposure. In our limited experience the thoracic extension has not adversely altered the operative or postoperative course."} {"id": "PMID:167200", "title": "A review of 100 renal and perinephric sonograms with anatomic diagnoses.", "content": "Sonography is a non-invasive safe, convenient, quick and pain-free diagnostic modality, which can differentiate fluid masses from solid tumors and give a 3-dimensional representation of organs and masses in the retroperitoneum by biplanar sections. Sonography depends on the fact that high frequency sound has many characteristics of light and is, in fact, a sophisticated method of transillumination. A review of the first 100 consecutive patients who had sonography and anatomic diagnosis of the renal or perinephric abnormality shows the versatility and potentials of sonography. Of these 100 sonograms of renal and perinephric abnormalities 92 were correct by anatomic diagnosis.", "contents": "A review of 100 renal and perinephric sonograms with anatomic diagnoses. Sonography is a non-invasive safe, convenient, quick and pain-free diagnostic modality, which can differentiate fluid masses from solid tumors and give a 3-dimensional representation of organs and masses in the retroperitoneum by biplanar sections. Sonography depends on the fact that high frequency sound has many characteristics of light and is, in fact, a sophisticated method of transillumination. A review of the first 100 consecutive patients who had sonography and anatomic diagnosis of the renal or perinephric abnormality shows the versatility and potentials of sonography. Of these 100 sonograms of renal and perinephric abnormalities 92 were correct by anatomic diagnosis."} {"id": "PMID:167201", "title": "Beware of the normal excretory urogram.", "content": "Excretory urography is not an infallible diagnostic procedure and should not be relied upon exclusively. A normal study must never result in the rejection of additional data derived from history, physical examination and laboratory tests. Two case histories are presented to underscore this caveat. Excretory urography must be supplemented additional radiographic evaluations when the conventional study fails to completely explain the clinical situation.", "contents": "Beware of the normal excretory urogram. Excretory urography is not an infallible diagnostic procedure and should not be relied upon exclusively. A normal study must never result in the rejection of additional data derived from history, physical examination and laboratory tests. Two case histories are presented to underscore this caveat. Excretory urography must be supplemented additional radiographic evaluations when the conventional study fails to completely explain the clinical situation."} {"id": "PMID:167203", "title": "A serologic survey of pronghorns in Alberta and Saskatchewan, 1970-1972.", "content": "To determine the exposure of free-ranging pronghorns (Antilocapra americana Ord) to selected pathogens, serum samples were obtained from 33 live-trapped animals from southwestern Saskatchewan in 1970, and from 26 and 51 animals from southeastern Alberta, in 1971 and 1972, respectively. Antibodies were found to the agents of parainfluenza 3, bovine virus diarrhea, eastern and western encephalomyelitis, infectious bovine rhinotracheitis and the chlamydial group. No serologic reactors were found to the agents of bluetongue, epizootic hemorrhagic disease, brucellosis, or leptospirosis (4 serotypes).", "contents": "A serologic survey of pronghorns in Alberta and Saskatchewan, 1970-1972. To determine the exposure of free-ranging pronghorns (Antilocapra americana Ord) to selected pathogens, serum samples were obtained from 33 live-trapped animals from southwestern Saskatchewan in 1970, and from 26 and 51 animals from southeastern Alberta, in 1971 and 1972, respectively. Antibodies were found to the agents of parainfluenza 3, bovine virus diarrhea, eastern and western encephalomyelitis, infectious bovine rhinotracheitis and the chlamydial group. No serologic reactors were found to the agents of bluetongue, epizootic hemorrhagic disease, brucellosis, or leptospirosis (4 serotypes)."} {"id": "PMID:167204", "title": "Herpersvirus strigis: host spectrum and distribution in infected owls.", "content": "Herpesvirus strigis, a new species of the genus Herpesvirus, is a pathogen for several species of owls in the order Srigiformes. Natural infection has been observed in the Eagle Owl (Bubo bubo L.), Long-eared Owl (Asio otus L.) and Snowy Owl (nyctea scandiaca L.) In addition the Little Owl (Athene noctua Scopolic) and Tengmalms Owl (Aegolius funereus L.) was experimentally infected. On the other hand the Tawny Owl (Strix aluco L.) and Barn Owl (Tyto albo Scopoli) proved resistant to a massive experimental infection. Of representatives from nine other orders of birds and mammals, only the Old World Kestrel (Falco tinnunculus L.) was found susceptible to this virus. Distribution of viral antigen in various organs of infected owls, as determined by immunofluorescence and by quantitative virus assay, was in accordance with the occurrence of macroscopic and microscopic lesions.", "contents": "Herpersvirus strigis: host spectrum and distribution in infected owls. Herpesvirus strigis, a new species of the genus Herpesvirus, is a pathogen for several species of owls in the order Srigiformes. Natural infection has been observed in the Eagle Owl (Bubo bubo L.), Long-eared Owl (Asio otus L.) and Snowy Owl (nyctea scandiaca L.) In addition the Little Owl (Athene noctua Scopolic) and Tengmalms Owl (Aegolius funereus L.) was experimentally infected. On the other hand the Tawny Owl (Strix aluco L.) and Barn Owl (Tyto albo Scopoli) proved resistant to a massive experimental infection. Of representatives from nine other orders of birds and mammals, only the Old World Kestrel (Falco tinnunculus L.) was found susceptible to this virus. Distribution of viral antigen in various organs of infected owls, as determined by immunofluorescence and by quantitative virus assay, was in accordance with the occurrence of macroscopic and microscopic lesions."} {"id": "PMID:167205", "title": "An outbreak of a hemorrhagic disease in white-tailed deer in Kentucky.", "content": "In 1971, an outbreak of a hemorrhagic disease occurred in captive and free-ranging white-tailed deer (Odocoileus virginianus) in Mammoth Cave National Park, Kentucky, Clinical signs and gross pathological lesions were consistent with those of epizootic hemorrhagic disease and bluetongue, as were serological and histopathological findings for samples sent to other laboratories. The infection rate among the 104 captive deer was 88-92%, and that among the free-ranging Park deer appeared to be similar. Mortality was negligible in the Park deer, but 65 (62%) of the captive deer died. The deaths were bimodally distributed over a 36-day period, and the mortality rate decreased from 97-100% for deer clinically ill during the first 17 days of the outbreak to 58% for deer first exhibiting clinical signs on day 16 or later. Mortality was equal in males and females, but less in yearlings than among fawns or adults. Winter mortality among survivors of the initial outbreak was associated with low ambient temperatures and sometimes fungal and bacterial abscesses, possibly sequelae or complications of the hemorrhagic disease. The pregnancy and birth rates among surviving does appeared to be normal.", "contents": "An outbreak of a hemorrhagic disease in white-tailed deer in Kentucky. In 1971, an outbreak of a hemorrhagic disease occurred in captive and free-ranging white-tailed deer (Odocoileus virginianus) in Mammoth Cave National Park, Kentucky, Clinical signs and gross pathological lesions were consistent with those of epizootic hemorrhagic disease and bluetongue, as were serological and histopathological findings for samples sent to other laboratories. The infection rate among the 104 captive deer was 88-92%, and that among the free-ranging Park deer appeared to be similar. Mortality was negligible in the Park deer, but 65 (62%) of the captive deer died. The deaths were bimodally distributed over a 36-day period, and the mortality rate decreased from 97-100% for deer clinically ill during the first 17 days of the outbreak to 58% for deer first exhibiting clinical signs on day 16 or later. Mortality was equal in males and females, but less in yearlings than among fawns or adults. Winter mortality among survivors of the initial outbreak was associated with low ambient temperatures and sometimes fungal and bacterial abscesses, possibly sequelae or complications of the hemorrhagic disease. The pregnancy and birth rates among surviving does appeared to be normal."} {"id": "PMID:167206", "title": "Cytomegalic inclusion disease in the east African headgehog.", "content": "Cytomegaly with intranuclear inclusion bodies was found in the duct epithelium of the salivary glands of five of ten hedgehogs (Atelerix albiventris). Cytomegalovirus infection was presumed to be the cause.", "contents": "Cytomegalic inclusion disease in the east African headgehog. Cytomegaly with intranuclear inclusion bodies was found in the duct epithelium of the salivary glands of five of ten hedgehogs (Atelerix albiventris). Cytomegalovirus infection was presumed to be the cause."} {"id": "PMID:167207", "title": "Fatal pox infection in a rough-legged hawk.", "content": "Natural pox infection occurred in a free-living rough-legged hawk (Buteo lagopus) in northeastern North Dakota. Gross, histological and electron microscopic findings were typical of pox infection, and characteristic lesions developed in red-tailed hawks (Buteo jamaicensis) but not in great horned owls (Bubo virginianus) following inoculation with case material. Death of the rough-legged hawk was attributed to starvation rsulting from inability to capture prey and to blood loss from foot lesions.", "contents": "Fatal pox infection in a rough-legged hawk. Natural pox infection occurred in a free-living rough-legged hawk (Buteo lagopus) in northeastern North Dakota. Gross, histological and electron microscopic findings were typical of pox infection, and characteristic lesions developed in red-tailed hawks (Buteo jamaicensis) but not in great horned owls (Bubo virginianus) following inoculation with case material. Death of the rough-legged hawk was attributed to starvation rsulting from inability to capture prey and to blood loss from foot lesions."} {"id": "PMID:167208", "title": "The pathogenicity of bovine strains of foot and mouth disease virus for impala and wildebeest.", "content": "Impala (Aepyceros melampus) and wildebeest (Connochaetes taurinus) were infected with bovine strains of foot and mouth disease virus by intradermolingual inoculation. No clinical signs developed in the impala but mild atypical lesions developed in the tongues of the wildebeest with generalized spread to one foot in two of the eight animals exposed. All the impala but only some of the wildebeest developed viraemia. No virus could be isolated from any tissues in either species after the 7th day following virus inoculation. Immune response occurred in both species. A field survey revealed few animals of either species with significant antibody titers and no virus 'carriers' were found.", "contents": "The pathogenicity of bovine strains of foot and mouth disease virus for impala and wildebeest. Impala (Aepyceros melampus) and wildebeest (Connochaetes taurinus) were infected with bovine strains of foot and mouth disease virus by intradermolingual inoculation. No clinical signs developed in the impala but mild atypical lesions developed in the tongues of the wildebeest with generalized spread to one foot in two of the eight animals exposed. All the impala but only some of the wildebeest developed viraemia. No virus could be isolated from any tissues in either species after the 7th day following virus inoculation. Immune response occurred in both species. A field survey revealed few animals of either species with significant antibody titers and no virus 'carriers' were found."} {"id": "PMID:167209", "title": "Herpes simplex virus in idiopathic facial paralysis (Bell palsy).", "content": "Sera from all 41 adult patients with idiopathic facil paralysis (Bell palsy) and 35 (85%) of 41 matched controls who had never had Bell palsy contained antibodies to herpes simplex virus (P smaller than.05). The frequency of antibodies to herpes zoster virus did not differ in patients and controls. A rise in antibody titer, indicating primary herpes simplex virus infection, was not found in these patients. That Bell palsy may be caused by reactivation of herpes simplex virus is suggested by (1) clinical, neurologic, laboratory, and immunologic similarities between idiopathic facial paralysis and known manifestations of reactivated herpes simplex virus infection, and (2) the known neurotropism of herpes simplex virus, including its presence in latent form in the trigeminal ganglia, and parallels with known facial paralysis due to varicella zoster virus, a closely related agent. The presence of antibodies to herpes simplex virus is the only common factor among the patients tested in this study.", "contents": "Herpes simplex virus in idiopathic facial paralysis (Bell palsy). Sera from all 41 adult patients with idiopathic facil paralysis (Bell palsy) and 35 (85%) of 41 matched controls who had never had Bell palsy contained antibodies to herpes simplex virus (P smaller than.05). The frequency of antibodies to herpes zoster virus did not differ in patients and controls. A rise in antibody titer, indicating primary herpes simplex virus infection, was not found in these patients. That Bell palsy may be caused by reactivation of herpes simplex virus is suggested by (1) clinical, neurologic, laboratory, and immunologic similarities between idiopathic facial paralysis and known manifestations of reactivated herpes simplex virus infection, and (2) the known neurotropism of herpes simplex virus, including its presence in latent form in the trigeminal ganglia, and parallels with known facial paralysis due to varicella zoster virus, a closely related agent. The presence of antibodies to herpes simplex virus is the only common factor among the patients tested in this study."} {"id": "PMID:167215", "title": "Methylxanthine induced small intestinal secretion.", "content": "Methylxanthines, being potent phosphodiesterase inhibitors, produce increased intestinal cyclic AMP levels and would be predicted to produce increased net intestinal fluid secretion. Their effect when presented to the intestinal lumen, which would be analogous to human ingestion, had not been previously determined. Isolated loops of rat jejunum were perfused with solutions of caffeine and theophylline in vivo. There was a decrease in net fluid absorption in both neonatal and mature animals exposed to theophylline. Mature animals exposed to caffeine developed a prompt secretory response, comparable to thax induced by cholera toxin. The data indicate that methylxanthines are potent intestinal secretagogues when administered intraluminally and suggest that secretory stimulation could be important in the gastrointestinal symptomatology elicited in man by these compounds.", "contents": "Methylxanthine induced small intestinal secretion. Methylxanthines, being potent phosphodiesterase inhibitors, produce increased intestinal cyclic AMP levels and would be predicted to produce increased net intestinal fluid secretion. Their effect when presented to the intestinal lumen, which would be analogous to human ingestion, had not been previously determined. Isolated loops of rat jejunum were perfused with solutions of caffeine and theophylline in vivo. There was a decrease in net fluid absorption in both neonatal and mature animals exposed to theophylline. Mature animals exposed to caffeine developed a prompt secretory response, comparable to thax induced by cholera toxin. The data indicate that methylxanthines are potent intestinal secretagogues when administered intraluminally and suggest that secretory stimulation could be important in the gastrointestinal symptomatology elicited in man by these compounds."} {"id": "PMID:167216", "title": "[Glomus tumors of the eyelids (author's transl)].", "content": "Two new observations of glomus tumors in the eyelid are reported, one of the angiomatous type, the other of the more adenoid type. The typical symptoms of other than ophthalmological localisations are described. The clinical diagnosis is possible. In the few cases reported by ophthalmologists the diagnosis is made by the histologist.", "contents": "[Glomus tumors of the eyelids (author's transl)]. Two new observations of glomus tumors in the eyelid are reported, one of the angiomatous type, the other of the more adenoid type. The typical symptoms of other than ophthalmological localisations are described. The clinical diagnosis is possible. In the few cases reported by ophthalmologists the diagnosis is made by the histologist."} {"id": "PMID:167229", "title": "Multiple Herpesvirus simiae isolation from a rhesus monkey which died of cerebral infarction.", "content": "A rhesus monkey housed in the New England Regional Primate Research Center for more than 4 yr died after an illness of 19 da. Clinical signs included central nervous system involvement and ulcers on the labial mucosa. Microscopically, the cause of death was established as multiple cerebral infarction. Lesions characteristic of herpesvirus infections were not present in the brain nor in any other tissue; however, Herpesvirus simiae was isolated from oral and anal swabs as well as from tongue and lung tissue. Inoculation of this agent in H simiae antibody negative rhesus monkeys resulted in infection, as indicated by virus isolation, serologic conversion, conjunctivitis, and development of ulcers at the mucoepithelial border, but fatal infection did not develop.", "contents": "Multiple Herpesvirus simiae isolation from a rhesus monkey which died of cerebral infarction. A rhesus monkey housed in the New England Regional Primate Research Center for more than 4 yr died after an illness of 19 da. Clinical signs included central nervous system involvement and ulcers on the labial mucosa. Microscopically, the cause of death was established as multiple cerebral infarction. Lesions characteristic of herpesvirus infections were not present in the brain nor in any other tissue; however, Herpesvirus simiae was isolated from oral and anal swabs as well as from tongue and lung tissue. Inoculation of this agent in H simiae antibody negative rhesus monkeys resulted in infection, as indicated by virus isolation, serologic conversion, conjunctivitis, and development of ulcers at the mucoepithelial border, but fatal infection did not develop."} {"id": "PMID:167230", "title": "Husbandry of the \"nude\" mouse in conventional and germfree environments.", "content": "The \"nude\" mouse is a unique tool for immunologic studies. Its relatively short life span dictates the application of rigid environmental controls to increase longevity if the mouse is to assume the role of a practical experimental animal. In this paper we discussed the husbandry procedures employed to raise \"nude\" mice in our facilities under conventional, defined flora, and germfree conditions. Conventional and defined flora mice were raised on laminar flow stay-clean rocks, and germfree \"nudes\" were housed in self-contained germfree isolators. The major cause of morbidity and mortality among conventional and defined flora \"nude\" mice was fulminating hepatitis. We presented evidence that the etiologic agent of the disease was mouse hepatitis virus (MHV). Germfree \"nude\" mice were completely free from viral and bacterial diseases.", "contents": "Husbandry of the \"nude\" mouse in conventional and germfree environments. The \"nude\" mouse is a unique tool for immunologic studies. Its relatively short life span dictates the application of rigid environmental controls to increase longevity if the mouse is to assume the role of a practical experimental animal. In this paper we discussed the husbandry procedures employed to raise \"nude\" mice in our facilities under conventional, defined flora, and germfree conditions. Conventional and defined flora mice were raised on laminar flow stay-clean rocks, and germfree \"nudes\" were housed in self-contained germfree isolators. The major cause of morbidity and mortality among conventional and defined flora \"nude\" mice was fulminating hepatitis. We presented evidence that the etiologic agent of the disease was mouse hepatitis virus (MHV). Germfree \"nude\" mice were completely free from viral and bacterial diseases."} {"id": "PMID:167231", "title": "Human vascular smooth muscle in culture. Growth and ultrastructure.", "content": "Mixed primary cultures of endothelial and smooth muscle cells were obtained from human umbilical cord vessels after prolonged collagenase digestion of their luminal surfaces. Morphologically homogeneous populations of vascular smooth muscle were then selectively isolated and subcultured for up to 16 weeks. Ultrastructurally, cultured cells were characterized by the presence of bundles of myofilaments with dense bodies similar to native umbilical vessel smooth muscle. Mature cultures developed a distinctive topographical organization consisting of bands of parallel cells and intertwined, multilayered areas. Elaborate intercellular attachments formed along contiguous cell surfaces. Large amounts of extracellular material accumulated, including amorphous substance, elastic fiber microfibrils, and 250- to 300-A,faintly-banded fibrils. In older cultures, focal proliferation, extracellular material secretion and cellular degeneration produced nodular protrusions somewhat resembling atherosclerotic lesions in vivo. Endothelium and smooth muscle cultured from this readily available human source may provide useful comparative material for pathophysiologic studies of vascular disease.", "contents": "Human vascular smooth muscle in culture. Growth and ultrastructure. Mixed primary cultures of endothelial and smooth muscle cells were obtained from human umbilical cord vessels after prolonged collagenase digestion of their luminal surfaces. Morphologically homogeneous populations of vascular smooth muscle were then selectively isolated and subcultured for up to 16 weeks. Ultrastructurally, cultured cells were characterized by the presence of bundles of myofilaments with dense bodies similar to native umbilical vessel smooth muscle. Mature cultures developed a distinctive topographical organization consisting of bands of parallel cells and intertwined, multilayered areas. Elaborate intercellular attachments formed along contiguous cell surfaces. Large amounts of extracellular material accumulated, including amorphous substance, elastic fiber microfibrils, and 250- to 300-A,faintly-banded fibrils. In older cultures, focal proliferation, extracellular material secretion and cellular degeneration produced nodular protrusions somewhat resembling atherosclerotic lesions in vivo. Endothelium and smooth muscle cultured from this readily available human source may provide useful comparative material for pathophysiologic studies of vascular disease."} {"id": "PMID:167232", "title": "Prevention of pulmonary vascular changes of chronic alveolar hypoxia by inhibition of angiotensin I-converting enzyme in the rat.", "content": "To test the hypothesis that the renin-angiotensin system is involved in the development of the pulmonary vascular patholigic changes of chronic alveolar hypoxia, two groups of rats were exposed to 0.5 atm. for 21 days. One group received SQ 20,881 (2 mg. per kg.) every 8 hours subcutaneously and the second group received normal saline. A third group of rats was maintained at normobaria. Rats receiving SQ 20,881 had significantly less pulmonary arterial hypertrophy and right ventricular hypertrophy than hypobaric animals. SQ 20,881-treated rats showed a significant increase in adrenal weight but a marked reduction in the thickness of the zona glomerulosa, as compared with the other groups. Our findings indicate that angiotensin II is necessary in the development of the pulmonary vascular structural changes of chronic alveolar hypoxia.", "contents": "Prevention of pulmonary vascular changes of chronic alveolar hypoxia by inhibition of angiotensin I-converting enzyme in the rat. To test the hypothesis that the renin-angiotensin system is involved in the development of the pulmonary vascular patholigic changes of chronic alveolar hypoxia, two groups of rats were exposed to 0.5 atm. for 21 days. One group received SQ 20,881 (2 mg. per kg.) every 8 hours subcutaneously and the second group received normal saline. A third group of rats was maintained at normobaria. Rats receiving SQ 20,881 had significantly less pulmonary arterial hypertrophy and right ventricular hypertrophy than hypobaric animals. SQ 20,881-treated rats showed a significant increase in adrenal weight but a marked reduction in the thickness of the zona glomerulosa, as compared with the other groups. Our findings indicate that angiotensin II is necessary in the development of the pulmonary vascular structural changes of chronic alveolar hypoxia."} {"id": "PMID:167233", "title": "The ultrastructure of the accessory sex organs of the male rat. 9. The effect of an antiandrogenic compound, SKF 22,340.", "content": "The coagulating gland and the dorsal lobe of the rat prostate were studied after administration of the antiandrogenic compound SKF 22,340. There was a general involution of the organs, with macroscopic atrophy and a reduced amount of secretory material. Ultrastructurally the cells contained fewer organelles as compared with the controls. There were also loss of cytoplasm and reduction both of cell height and width. Within the dorsal lobe, prominent nuclear and nucleolar changes were found. The alterations observed in the present study are similar to changes which were found in animals treated with another antiandrogenic compound, cyproterone acetate. The results are discussed in relation to the available biochemical data.", "contents": "The ultrastructure of the accessory sex organs of the male rat. 9. The effect of an antiandrogenic compound, SKF 22,340. The coagulating gland and the dorsal lobe of the rat prostate were studied after administration of the antiandrogenic compound SKF 22,340. There was a general involution of the organs, with macroscopic atrophy and a reduced amount of secretory material. Ultrastructurally the cells contained fewer organelles as compared with the controls. There were also loss of cytoplasm and reduction both of cell height and width. Within the dorsal lobe, prominent nuclear and nucleolar changes were found. The alterations observed in the present study are similar to changes which were found in animals treated with another antiandrogenic compound, cyproterone acetate. The results are discussed in relation to the available biochemical data."} {"id": "PMID:167234", "title": "Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice.", "content": "Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation.", "contents": "Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice. Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation."} {"id": "PMID:167241", "title": "Liver disease of the alcoholic.", "content": "Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.", "contents": "Liver disease of the alcoholic. Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis."} {"id": "PMID:167239", "title": "Adrenergic beta-receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age.", "content": "The relaxing effect of isoproterenol on aortic strips from rats decreases and disappears with increasing age of the animal. In aortas from young rats (1 month) the cAMP level increases after stimulation with isoproterenol (3.6 muM), whereas in old aortas (6 months) the cAMP level was unchanged. Basal and NaF stimulated adenyl cyclase activities are increased in aortas from rats 6 months of age compared with those one month old. The phosphodiesterase activities decrease with increasing age both low (10-7M) and high (10-4M) substrate concentration.", "contents": "Adrenergic beta-receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age. The relaxing effect of isoproterenol on aortic strips from rats decreases and disappears with increasing age of the animal. In aortas from young rats (1 month) the cAMP level increases after stimulation with isoproterenol (3.6 muM), whereas in old aortas (6 months) the cAMP level was unchanged. Basal and NaF stimulated adenyl cyclase activities are increased in aortas from rats 6 months of age compared with those one month old. The phosphodiesterase activities decrease with increasing age both low (10-7M) and high (10-4M) substrate concentration."} {"id": "PMID:167248", "title": "Nasopharyngeal angiofibroma in the elderly: report of a case.", "content": "Although nasopharyngeal angiofibromas usually occur during puberty and adolescence, thus being considered as juvenile, very rare documented reports describe this condition in old persons. The case of a 62-year-old man with a nasopharyngeal angiofibroma successfully resected is presented. It was the only lesion found in an old individual among 283 cases seen during a 20-year period in a large city hospital.", "contents": "Nasopharyngeal angiofibroma in the elderly: report of a case. Although nasopharyngeal angiofibromas usually occur during puberty and adolescence, thus being considered as juvenile, very rare documented reports describe this condition in old persons. The case of a 62-year-old man with a nasopharyngeal angiofibroma successfully resected is presented. It was the only lesion found in an old individual among 283 cases seen during a 20-year period in a large city hospital."} {"id": "PMID:167249", "title": "IV. Multiple glomus tumors in the head and neck.", "content": "Eight of 76 glomus tumors in the head and neck region are multiple. The most common association is with carotid body tumors; the most common pattern is an ipsilateral glomus tympanicum and carotid body tumor. The approach to clinical evaluation is based on a complete otolaryngologic, neurologic, and neuroradiologic evaluation of all patients with glomus tumors. The rationale for priorities in management is the resection of the most dangerous lesions first. This study confirms the previous observations that glomus tumors have a definite proclivity for multicentricity (10 percent) and a high incidence for other associated malignancies (8 percent).", "contents": "IV. Multiple glomus tumors in the head and neck. Eight of 76 glomus tumors in the head and neck region are multiple. The most common association is with carotid body tumors; the most common pattern is an ipsilateral glomus tympanicum and carotid body tumor. The approach to clinical evaluation is based on a complete otolaryngologic, neurologic, and neuroradiologic evaluation of all patients with glomus tumors. The rationale for priorities in management is the resection of the most dangerous lesions first. This study confirms the previous observations that glomus tumors have a definite proclivity for multicentricity (10 percent) and a high incidence for other associated malignancies (8 percent)."} {"id": "PMID:167258", "title": "Lipd profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats.", "content": "Three major density classes of lipoproteins and a residual protein (d greater than 1.21) were isolated by ultracentrifugation from plasma of fasted, fed normal, and choline-deficient rats. Lipid extracts were obtained from total plasma and the various density classes of lipoproteins, and each extract was examined in detail by thin layer and gas chromatographies. The results indicated essentially identical compositions of molecular species of phosphatidyl choline, which suggested their rapid equilibration among the different plasma lipoprotein classes. In contrast, the molecular species of the triacylglycerols and cholesteryl esters showed significant differences among the chylomicrons, very low and low, and high density lipoproteins, which excluded the possibility of their ready equilibration in vivo. Omission of choline from diet resulted in a sharp and statistically significant decrease in all lipid components of the very low and low density lipoproteins with 2 days. After 10 days of choline deficiency, the lipid levels of chylomicrons and very low and low density lipoproteins were ca. one-half the levels found in the choline supplemented animals, and there were discernible distortions in their lipid composition. Reintroduction of choline led to a prompt return to normal levels and lipid composition of both chylomicron and very low and low density lipoprotein fractions. The lack of equilibration of the triacylglycerols among the lipoprotein classes under normal conditions and in choline deficiency demonstrates an as yet unrecgnized source of compartmentation of plasma lipids.", "contents": "Lipd profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats. Three major density classes of lipoproteins and a residual protein (d greater than 1.21) were isolated by ultracentrifugation from plasma of fasted, fed normal, and choline-deficient rats. Lipid extracts were obtained from total plasma and the various density classes of lipoproteins, and each extract was examined in detail by thin layer and gas chromatographies. The results indicated essentially identical compositions of molecular species of phosphatidyl choline, which suggested their rapid equilibration among the different plasma lipoprotein classes. In contrast, the molecular species of the triacylglycerols and cholesteryl esters showed significant differences among the chylomicrons, very low and low, and high density lipoproteins, which excluded the possibility of their ready equilibration in vivo. Omission of choline from diet resulted in a sharp and statistically significant decrease in all lipid components of the very low and low density lipoproteins with 2 days. After 10 days of choline deficiency, the lipid levels of chylomicrons and very low and low density lipoproteins were ca. one-half the levels found in the choline supplemented animals, and there were discernible distortions in their lipid composition. Reintroduction of choline led to a prompt return to normal levels and lipid composition of both chylomicron and very low and low density lipoprotein fractions. The lack of equilibration of the triacylglycerols among the lipoprotein classes under normal conditions and in choline deficiency demonstrates an as yet unrecgnized source of compartmentation of plasma lipids."} {"id": "PMID:167259", "title": "Phospholipase C catalyzed formation of sphinogomyelin--14C from lecithin and N-(-14C)-oleoyl-sphingosine.", "content": "Commercial preparations of Clostreidium perfringens were incubated with phosphatidyl choline and N-1-(-14C) oleoylsphingosine. A radioactive product was formed which cochromatogramed with spingomyelin standard in three different solvent systems. Several other phospholipases and phosphatases were unable to catalyze this reaction. Neither choline, phosphoryl choline, cytidine diphosphate choline nor p-nitrophenyl phosphoryl choline were acitve donors. Sphingomyelin was only slightly active as a phosphoryl choline donor.", "contents": "Phospholipase C catalyzed formation of sphinogomyelin--14C from lecithin and N-(-14C)-oleoyl-sphingosine. Commercial preparations of Clostreidium perfringens were incubated with phosphatidyl choline and N-1-(-14C) oleoylsphingosine. A radioactive product was formed which cochromatogramed with spingomyelin standard in three different solvent systems. Several other phospholipases and phosphatases were unable to catalyze this reaction. Neither choline, phosphoryl choline, cytidine diphosphate choline nor p-nitrophenyl phosphoryl choline were acitve donors. Sphingomyelin was only slightly active as a phosphoryl choline donor."} {"id": "PMID:167260", "title": "Sterospecific analysis of hepatoma, host liver, and normal rat liver triglycerides from animals on chow and fat free diets.", "content": "Triglycerides from normal liver, host liver, and heptoma of rats maintained on chow and fat-free diets were subjected to sterospecific analysis. Normal and host liver triglycerides from animals on the same diet did not exhibit significant differences. Fat-free diet reduced polyunsaturated fatty acids in normal and in host liver triglycerides. Each position of hepatoma and liver triglyceride glycerol exhibited a characteristic fatty acid composition. Palmitate concentrations were reduced dramatically and stearate levels were increased significantly at the 1 position of hepatoma triglycerides, relative to the corresponding position of liver triglycerides which were affected little by diet ot tumor. Except for higher percentages of C-20 and higher fatty acids, common to all three positions, the composition of hepatoma triglycerides at the 2 position appeared normal. The 3 position of hepatoma triglycerides contained significantly higher percentages of stearate than liver. Data obtained previously for Ehrlich ascites cell triglycerides were in good agreement with this hepatoma. Data from these two neoplasms suggest that the metabolic system that regulates or controls the fatty acid composition at the 1 and 3 positions of normal tissue triglycerides does not function normally in neoplasms.", "contents": "Sterospecific analysis of hepatoma, host liver, and normal rat liver triglycerides from animals on chow and fat free diets. Triglycerides from normal liver, host liver, and heptoma of rats maintained on chow and fat-free diets were subjected to sterospecific analysis. Normal and host liver triglycerides from animals on the same diet did not exhibit significant differences. Fat-free diet reduced polyunsaturated fatty acids in normal and in host liver triglycerides. Each position of hepatoma and liver triglyceride glycerol exhibited a characteristic fatty acid composition. Palmitate concentrations were reduced dramatically and stearate levels were increased significantly at the 1 position of hepatoma triglycerides, relative to the corresponding position of liver triglycerides which were affected little by diet ot tumor. Except for higher percentages of C-20 and higher fatty acids, common to all three positions, the composition of hepatoma triglycerides at the 2 position appeared normal. The 3 position of hepatoma triglycerides contained significantly higher percentages of stearate than liver. Data obtained previously for Ehrlich ascites cell triglycerides were in good agreement with this hepatoma. Data from these two neoplasms suggest that the metabolic system that regulates or controls the fatty acid composition at the 1 and 3 positions of normal tissue triglycerides does not function normally in neoplasms."} {"id": "PMID:167261", "title": "Biosynthesis and structure of glycosyl diglycerides, steryl glucosides, and acylated steryl glucosides.", "content": "A particulate enzyme fraction from Mycobacterim smegmatis catalyzed the transfer of -14C-glucose from the UDP--14C-glucose into neutral glycolipids. The two major radioactive components were purified by column chromatography on O-diethylamino ethyl cellulose (acetate) and thin layer chromatography on silica gel in several solvents. The first product yielded a water-soluble component upon saponification, which had a hexoseglycerol ratio of 1:1 with all of the hexose being identified as glucose. The second product yielded a water-soluble component upon saponification which contained hexose and glycerol in a 2:1 ratio and, in addition to glucose, contained lesser amounts of mannose and galactose. Palmitate and oleate were the predominant fatty acids and were present in equimolar amounts. The products thus have been identified as monoglycosyldiglyceride and diglycosyldiglyceride. The diglycosyldiglyceride could also be labeled with -14C-galactose when UDP--14C-galactose served as the donor, but the monoglycosyldiglyceride was only slightly labeled with -14C-galactose. Membrane fractions from mung bean seedlings catalyzed the transfer of -14C-glucose from UDP--14C-glucose into a neutral glycolipid which has been purified by thin layer chromatography and analyzed by combined gas liquid chromatography-mass spectrometry. It was determined to be a steryl glucoside with the two major sterol components being betasitosterol and stigmasterol linked to beta-D-glucose. Particulate fractions from developing cotton fibers also catalyzed the formation of steryl glucosides and, in addition, they catalyzed the esterification of steryl glucosides at the 6 position of glucose with fatty acids (primarily palmitate and oleate) from an andogenous acyl donor. Both the glucosyl transferase and the acyltransferase have been solubilized with Triton X-100 and partially purified by chromatography on Sephadex G-200. The acyltransferase activity was reconstituted by the addition of the steryl glucoside and a phospholipid acyl donor.", "contents": "Biosynthesis and structure of glycosyl diglycerides, steryl glucosides, and acylated steryl glucosides. A particulate enzyme fraction from Mycobacterim smegmatis catalyzed the transfer of -14C-glucose from the UDP--14C-glucose into neutral glycolipids. The two major radioactive components were purified by column chromatography on O-diethylamino ethyl cellulose (acetate) and thin layer chromatography on silica gel in several solvents. The first product yielded a water-soluble component upon saponification, which had a hexoseglycerol ratio of 1:1 with all of the hexose being identified as glucose. The second product yielded a water-soluble component upon saponification which contained hexose and glycerol in a 2:1 ratio and, in addition to glucose, contained lesser amounts of mannose and galactose. Palmitate and oleate were the predominant fatty acids and were present in equimolar amounts. The products thus have been identified as monoglycosyldiglyceride and diglycosyldiglyceride. The diglycosyldiglyceride could also be labeled with -14C-galactose when UDP--14C-galactose served as the donor, but the monoglycosyldiglyceride was only slightly labeled with -14C-galactose. Membrane fractions from mung bean seedlings catalyzed the transfer of -14C-glucose from UDP--14C-glucose into a neutral glycolipid which has been purified by thin layer chromatography and analyzed by combined gas liquid chromatography-mass spectrometry. It was determined to be a steryl glucoside with the two major sterol components being betasitosterol and stigmasterol linked to beta-D-glucose. Particulate fractions from developing cotton fibers also catalyzed the formation of steryl glucosides and, in addition, they catalyzed the esterification of steryl glucosides at the 6 position of glucose with fatty acids (primarily palmitate and oleate) from an andogenous acyl donor. Both the glucosyl transferase and the acyltransferase have been solubilized with Triton X-100 and partially purified by chromatography on Sephadex G-200. The acyltransferase activity was reconstituted by the addition of the steryl glucoside and a phospholipid acyl donor."} {"id": "PMID:167262", "title": "Inhibtion of diplopterol synthesis in Tetrahymena pyriformis by a hypocholesteremic compound.", "content": "The hypocholesteremic compound, 3beta-(beta-dimethylaminoethoxy)-androst-5-en-17-one was earlier shown to inhibit the synthesis of tetrahymanol and two undentified lipids. It now has been demonstrated that one of the unidentified compounds is diplopterol.", "contents": "Inhibtion of diplopterol synthesis in Tetrahymena pyriformis by a hypocholesteremic compound. The hypocholesteremic compound, 3beta-(beta-dimethylaminoethoxy)-androst-5-en-17-one was earlier shown to inhibit the synthesis of tetrahymanol and two undentified lipids. It now has been demonstrated that one of the unidentified compounds is diplopterol."} {"id": "PMID:167263", "title": "Effects of repeated endurance exercise on serum enzyme activities in well-conditioned males.", "content": "Daily fluctuations in serum enzyme activities during distance running in 3 well-conditioned males were measured for 8 consecutive days. During the study the exercise regimen comprised 8 mile runs on days 1, 2 and 5; a 10.5 mile run on day 3; a 15 mile run on day 4 and resting on days 6-8. Heart rate, rectal temperature, hematocrit, plasma hemoglobin, creatine phosphokinase (CPK, glutamic-oxaloacetic and glutamic-pyruvic transaminases, lactate dehydrogenase (LDH), adenylate kinase (AK), and lactate and pyruvate were measured before and after exercise and during the resting days. Significant increases occurred in heart rate and rectal temperature with each run but were unrelated to enzyme levels. Pre-exercise CPK levels, 49 plus or minus 1 mIU/ml on day 1, rose progressively to 123 plus or minus 25 mIU/ml on day 5, and returned to initial control levels by day 8. Post-exercise CPK levels were significantly greater than pre-exercise levels on each running day but were unrelated to the severity of the exercise. LDH and AK levels did not significantly change with the exercise stress, but pre-exercise AK levels in these trained males were higher than values in non-trained males (10-20 vs. 0-5 mIU/ml) (3). Post-exercise enzyme levels appeared unrelated to final heart rate, rectal temperature or plasma hemoglobin. These results suggest that (1) CPK, unlike the other enzymes studied, is a sensitive index of exercise stress in well-conditioned runners and (2) elevated CPK and AK levels in such runners represent physiologic responses. Appropriate caution should be used in making clinical judgements from these enzyme assays in trained individuals.", "contents": "Effects of repeated endurance exercise on serum enzyme activities in well-conditioned males. Daily fluctuations in serum enzyme activities during distance running in 3 well-conditioned males were measured for 8 consecutive days. During the study the exercise regimen comprised 8 mile runs on days 1, 2 and 5; a 10.5 mile run on day 3; a 15 mile run on day 4 and resting on days 6-8. Heart rate, rectal temperature, hematocrit, plasma hemoglobin, creatine phosphokinase (CPK, glutamic-oxaloacetic and glutamic-pyruvic transaminases, lactate dehydrogenase (LDH), adenylate kinase (AK), and lactate and pyruvate were measured before and after exercise and during the resting days. Significant increases occurred in heart rate and rectal temperature with each run but were unrelated to enzyme levels. Pre-exercise CPK levels, 49 plus or minus 1 mIU/ml on day 1, rose progressively to 123 plus or minus 25 mIU/ml on day 5, and returned to initial control levels by day 8. Post-exercise CPK levels were significantly greater than pre-exercise levels on each running day but were unrelated to the severity of the exercise. LDH and AK levels did not significantly change with the exercise stress, but pre-exercise AK levels in these trained males were higher than values in non-trained males (10-20 vs. 0-5 mIU/ml) (3). Post-exercise enzyme levels appeared unrelated to final heart rate, rectal temperature or plasma hemoglobin. These results suggest that (1) CPK, unlike the other enzymes studied, is a sensitive index of exercise stress in well-conditioned runners and (2) elevated CPK and AK levels in such runners represent physiologic responses. Appropriate caution should be used in making clinical judgements from these enzyme assays in trained individuals."} {"id": "PMID:167264", "title": "The bone marrow in multiple myeloma: correlation of plasma cell ultrastructure and clinical state.", "content": "The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation.", "contents": "The bone marrow in multiple myeloma: correlation of plasma cell ultrastructure and clinical state. The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation."} {"id": "PMID:167265", "title": "Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans.", "content": "The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.", "contents": "Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans. The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue."} {"id": "PMID:167266", "title": "Apolipoproteins in human pregnancy.", "content": "Apolipoproteins are important in the structure and metabolism of lipoproteins, and alterations in levels of apoproteins or in their interrelations occur in some forms of hyperlipemia. Pregnancy is regularly accompanied by hyperlipoproteinemia, but while data on lipoprotein lipids is available, the apopipoproteins have not been studied. To characterize the lipemia of pregnancy more completely, we studied some of the apolipoproteins in plasmas of pregnancy women. Thirty-eight normal fasting women were studied between the 18th and 39th weeks of gestation and again 23 plus or minus 17 weeks after delivery. Eight additional women were sampled every 4-6 wk during the second and third trimesters of gestation. Plasma and lipoprotein lipids were assayed by standard procedures and Apolipoprotein B (ApoB) was measured by radioimmunoassay. The interrelations of Apolipoprotein A (ApoA) in high-density lipoprotein (HDL) and of Apolipoprotein C (ApoC) in very-low-density lipoprotein (VLDL) were assessed by disc gel electrophoresis in four women during the last trimester of gestation and again 6-8 mo post partum and in four nongravid controls. Gestational triglycerides (TG) and cholesterol (Chol) were elevated in 95% of the pregnant women. TG in lipoproteins rose progressively during gestation, with VLDL-TG rising the most. Low-density lipoprotein (LDL) and HDL became enriched by TG relative to other components. Total-and VLDL-ApoB increased, while LDL-ApoB remained unchanged, resulting in a change in the density distribution of ApoB. (VLDL-ApoB X 100/total ApoB rose from 3.6% to 6.7%, P less than 0.02.) The accumulation of TG-rich LDL and the increases of VLDL-ApoB may be the result of changes in the rates of secretion or intravascular catabolism of VLDL. Which process is altered remains to be determined. The relative amounts of ApoC-II and ApoC-III in VLDL and the ApoA-I/ApoA-II ratios in HDL were unchanged in pregnancy. These results differ from those seen following high-carbohydrate diets.", "contents": "Apolipoproteins in human pregnancy. Apolipoproteins are important in the structure and metabolism of lipoproteins, and alterations in levels of apoproteins or in their interrelations occur in some forms of hyperlipemia. Pregnancy is regularly accompanied by hyperlipoproteinemia, but while data on lipoprotein lipids is available, the apopipoproteins have not been studied. To characterize the lipemia of pregnancy more completely, we studied some of the apolipoproteins in plasmas of pregnancy women. Thirty-eight normal fasting women were studied between the 18th and 39th weeks of gestation and again 23 plus or minus 17 weeks after delivery. Eight additional women were sampled every 4-6 wk during the second and third trimesters of gestation. Plasma and lipoprotein lipids were assayed by standard procedures and Apolipoprotein B (ApoB) was measured by radioimmunoassay. The interrelations of Apolipoprotein A (ApoA) in high-density lipoprotein (HDL) and of Apolipoprotein C (ApoC) in very-low-density lipoprotein (VLDL) were assessed by disc gel electrophoresis in four women during the last trimester of gestation and again 6-8 mo post partum and in four nongravid controls. Gestational triglycerides (TG) and cholesterol (Chol) were elevated in 95% of the pregnant women. TG in lipoproteins rose progressively during gestation, with VLDL-TG rising the most. Low-density lipoprotein (LDL) and HDL became enriched by TG relative to other components. Total-and VLDL-ApoB increased, while LDL-ApoB remained unchanged, resulting in a change in the density distribution of ApoB. (VLDL-ApoB X 100/total ApoB rose from 3.6% to 6.7%, P less than 0.02.) The accumulation of TG-rich LDL and the increases of VLDL-ApoB may be the result of changes in the rates of secretion or intravascular catabolism of VLDL. Which process is altered remains to be determined. The relative amounts of ApoC-II and ApoC-III in VLDL and the ApoA-I/ApoA-II ratios in HDL were unchanged in pregnancy. These results differ from those seen following high-carbohydrate diets."} {"id": "PMID:167267", "title": "Intestinal amoebiasis and amoebic liver abscess in Brisbane, 1956 to 1973. Clinical syndromes and the results of medical and surgical management.", "content": "Nineteen patients presented to teaching hospitals in Brisbane with symptomatic amoebiasis from 1965 to 1973. The majority of patients gave a history of overseas travel or residence. Intestinal amoebiasis most frequently occurred in its non-dysenteric form, so that there were some problems in differentiating it from more commonly occurring forms of colitis. The potential for amoeboma to be mistaken for a neoplasm was evident. Amoebic liver abscess was confirmed in 10 cases and, in nine of these, the abscess was localized to the right lobe of the liver. A total colectomy had been performed in one case and an abdominoperineal resection of the rectum in another before hospital admission in Brisbane and confirmation of the diagnosis of amoebiasis. Five of the patients with amoebic liver abscess underwent laparotomy soon after admission because of upper abdominal symptoms and signs which resembled those of other surgical conditions. Although the indirect haemagglutination test was of considerable assistance in diagnosing amoebiasis, it was apparent that attention to detail in the collection and examination of faecal specimens remained of major importance. A trial of metronidazole, which is both effective and relatively safe, is advocated in cases of diagnostic difficulty, when amoebiasis is suspected but unproven, and when the adoption of an alternative diagnosis would lead to the initiation of less satisfactory drug therapy or involve otherwise unnecessary surgery.", "contents": "Intestinal amoebiasis and amoebic liver abscess in Brisbane, 1956 to 1973. Clinical syndromes and the results of medical and surgical management. Nineteen patients presented to teaching hospitals in Brisbane with symptomatic amoebiasis from 1965 to 1973. The majority of patients gave a history of overseas travel or residence. Intestinal amoebiasis most frequently occurred in its non-dysenteric form, so that there were some problems in differentiating it from more commonly occurring forms of colitis. The potential for amoeboma to be mistaken for a neoplasm was evident. Amoebic liver abscess was confirmed in 10 cases and, in nine of these, the abscess was localized to the right lobe of the liver. A total colectomy had been performed in one case and an abdominoperineal resection of the rectum in another before hospital admission in Brisbane and confirmation of the diagnosis of amoebiasis. Five of the patients with amoebic liver abscess underwent laparotomy soon after admission because of upper abdominal symptoms and signs which resembled those of other surgical conditions. Although the indirect haemagglutination test was of considerable assistance in diagnosing amoebiasis, it was apparent that attention to detail in the collection and examination of faecal specimens remained of major importance. A trial of metronidazole, which is both effective and relatively safe, is advocated in cases of diagnostic difficulty, when amoebiasis is suspected but unproven, and when the adoption of an alternative diagnosis would lead to the initiation of less satisfactory drug therapy or involve otherwise unnecessary surgery."} {"id": "PMID:167268", "title": "Virus isolation and titration at 33 degrees and 37 degrees C.", "content": "Various prototype viruses and original specimens were comparatively titrated in cell cultures at 33 degrees and 37 degrees C. Higher titers at 37 degrees were consistently obtained with adenoviruses; for other viruses (enteroviruses, herpesvirus hominis, vaccinia virus, parainfluenza viruses) the titers were mostly identical at either temperature. Original specimens and prototye strains showed the same behavior. The habit to cultivate viruses from throat swabs at 33 degrees C is unsatisfactory for adenoviruses.", "contents": "Virus isolation and titration at 33 degrees and 37 degrees C. Various prototype viruses and original specimens were comparatively titrated in cell cultures at 33 degrees and 37 degrees C. Higher titers at 37 degrees were consistently obtained with adenoviruses; for other viruses (enteroviruses, herpesvirus hominis, vaccinia virus, parainfluenza viruses) the titers were mostly identical at either temperature. Original specimens and prototye strains showed the same behavior. The habit to cultivate viruses from throat swabs at 33 degrees C is unsatisfactory for adenoviruses."} {"id": "PMID:167269", "title": "False positive rubella virus haemagglutination inhibition reactions: occurrence and disclosure.", "content": "A floatation centrifugation procedure is described by which antibodies and non-specific rubella virus haemagglutination inhibitors can be completely separated. Using this method it was shown that false positive reactions occur with the conventional pretreatments of sera for removing inhibitors, especially with the heparin-McCl2 procedure. Other methods for removal of inhibitors were examined in view of recent knowledge about the chemical nature of the inhibitors. Treatment with phospholipase C proved useful for disclosure of false positive reactions, while floatation centrifugation was the most sensitive method for demonstration of low antibody concentrations.", "contents": "False positive rubella virus haemagglutination inhibition reactions: occurrence and disclosure. A floatation centrifugation procedure is described by which antibodies and non-specific rubella virus haemagglutination inhibitors can be completely separated. Using this method it was shown that false positive reactions occur with the conventional pretreatments of sera for removing inhibitors, especially with the heparin-McCl2 procedure. Other methods for removal of inhibitors were examined in view of recent knowledge about the chemical nature of the inhibitors. Treatment with phospholipase C proved useful for disclosure of false positive reactions, while floatation centrifugation was the most sensitive method for demonstration of low antibody concentrations."} {"id": "PMID:167278", "title": "The effect of azide on the spectral and catalytic properties of ascorbate oxidase.", "content": "(1) 45% of the total copper of green zucchini ascorbate oxidase is EPR-detectable. At least two species of copper are present, one with a small A parallel (Type 1) and one with a large A parallel (Type 2). Computer simulated spectra indicated 50% contribution by each type of copper. (2) Azide inhibited ascorbate oxidase activity by an uncompetitive mechanism. EPR and optical spectra performed on titration of ascorbate oxidase with azide indicated the formation of a copper-azide complex. The Type 2 copper appears to be the binding site of azide. The involvement of the EPR non-detectable copper as an anion binding site with high affinity toward azide can not be excluded.", "contents": "The effect of azide on the spectral and catalytic properties of ascorbate oxidase. (1) 45% of the total copper of green zucchini ascorbate oxidase is EPR-detectable. At least two species of copper are present, one with a small A parallel (Type 1) and one with a large A parallel (Type 2). Computer simulated spectra indicated 50% contribution by each type of copper. (2) Azide inhibited ascorbate oxidase activity by an uncompetitive mechanism. EPR and optical spectra performed on titration of ascorbate oxidase with azide indicated the formation of a copper-azide complex. The Type 2 copper appears to be the binding site of azide. The involvement of the EPR non-detectable copper as an anion binding site with high affinity toward azide can not be excluded."} {"id": "PMID:167279", "title": "Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12.", "content": "The dam-3 mutation results in a five-fold reduction in the number of 6-methyl-adenine (6-meA) residues in the DNA of E. coli K12 or phage lambda. The DNA of phage fd appears to be devoid of 6-meA when propagated on dam-3 bacteria. The phenotypic differences between dam-3 and dam+ bacteria include: (i) increased free phage in lysogenic dam-3 cultures, (2) increased sensitivity to methyl methanesulfonate (MMS), (3) inviability of dam-3 lex-I strains, (4) lower molecular weight of DNA in dam-3 bacteria in the absence of DNA ligase and (5) increased rate of DNA degradation in dam-3 recA strains.", "contents": "Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12. The dam-3 mutation results in a five-fold reduction in the number of 6-methyl-adenine (6-meA) residues in the DNA of E. coli K12 or phage lambda. The DNA of phage fd appears to be devoid of 6-meA when propagated on dam-3 bacteria. The phenotypic differences between dam-3 and dam+ bacteria include: (i) increased free phage in lysogenic dam-3 cultures, (2) increased sensitivity to methyl methanesulfonate (MMS), (3) inviability of dam-3 lex-I strains, (4) lower molecular weight of DNA in dam-3 bacteria in the absence of DNA ligase and (5) increased rate of DNA degradation in dam-3 recA strains."} {"id": "PMID:167280", "title": "Mutagenicity testing with Salmonella typhimurium strains. II. The effect of unusual phenotypes on the mutagenic response.", "content": "The enhanced sensitivity of some Salmonella typhimurium strains to the mutagenic action of a number of chemicals appears to be due to the defect in the uvrB gene product and not to an inability to produce H-2-S or to the absence of formic acid hydrogenlyase which also characterizes these strains.", "contents": "Mutagenicity testing with Salmonella typhimurium strains. II. The effect of unusual phenotypes on the mutagenic response. The enhanced sensitivity of some Salmonella typhimurium strains to the mutagenic action of a number of chemicals appears to be due to the defect in the uvrB gene product and not to an inability to produce H-2-S or to the absence of formic acid hydrogenlyase which also characterizes these strains."} {"id": "PMID:167293", "title": "Comparative studies on the biological activities of cardiotoxin, melittin and prymnesin.", "content": "The actions of cardiotoxin (CTX), melittin and prymnesin were compared on dog erythrocytes, chicken biventer cervicis muscle, rabbit conjunctiva, acetylcholinesterase, succinate-cytochrome c reductase and turbidity of the rat liver mitochondrial suspension. 1. CTX and melittin were approximately equipotent in the various biological activities, while prymnesin was not. 2. The rate of direct ehmolysis induced by CTX was slow, while that induced by either melittin or prymnesin was fast. 3. Phosphate ions, 10mM Ca++, as well as 1 mM reduced glutathione, considerably inhibited the CTX-induced hemolysis, but only slightly inhibited that induced by melittin or prymnesin. 4. CTX, melittin and prymnesin caused contracture of the chicken biventer cervicis muscle. Prymnesin was much less active in this preparation as compared with its hemolytic potency. The CTX contracture was completely inhibited by high Ca++ (10mM) medium, while the melittin contracture was not. 5. The rate of CTX contracture to reach the peak tension was increased when the concentration of CTX was increased, while the rate of melittin contracture did not change very much as the concentrations varied. 6. All three toxins caused a local irritation of the conjunctival sac of the rabbit eye. 7. Both CTX and melittin inhibited acetylcholinesterase and succinate-cytochrome c reductase activities, and also increased the turbidity of the rat liver mitochondrial suspension, while prymnesin was totally inactive in these respects. It is concluded that the mechanism of actions of these toxins may be different at the molecular level. The role of the detergent properties of these toxins in their biological activities is discussed.", "contents": "Comparative studies on the biological activities of cardiotoxin, melittin and prymnesin. The actions of cardiotoxin (CTX), melittin and prymnesin were compared on dog erythrocytes, chicken biventer cervicis muscle, rabbit conjunctiva, acetylcholinesterase, succinate-cytochrome c reductase and turbidity of the rat liver mitochondrial suspension. 1. CTX and melittin were approximately equipotent in the various biological activities, while prymnesin was not. 2. The rate of direct ehmolysis induced by CTX was slow, while that induced by either melittin or prymnesin was fast. 3. Phosphate ions, 10mM Ca++, as well as 1 mM reduced glutathione, considerably inhibited the CTX-induced hemolysis, but only slightly inhibited that induced by melittin or prymnesin. 4. CTX, melittin and prymnesin caused contracture of the chicken biventer cervicis muscle. Prymnesin was much less active in this preparation as compared with its hemolytic potency. The CTX contracture was completely inhibited by high Ca++ (10mM) medium, while the melittin contracture was not. 5. The rate of CTX contracture to reach the peak tension was increased when the concentration of CTX was increased, while the rate of melittin contracture did not change very much as the concentrations varied. 6. All three toxins caused a local irritation of the conjunctival sac of the rabbit eye. 7. Both CTX and melittin inhibited acetylcholinesterase and succinate-cytochrome c reductase activities, and also increased the turbidity of the rat liver mitochondrial suspension, while prymnesin was totally inactive in these respects. It is concluded that the mechanism of actions of these toxins may be different at the molecular level. The role of the detergent properties of these toxins in their biological activities is discussed."} {"id": "PMID:167294", "title": "The in vitro effects of vinblastine and vincristine on the responses of the guinea-pig vas deferens to nerve stimulation.", "content": "1. Neither vinblastine nor vincristine (1x10-4M) appeared to cause a specific blockade of transmission through the guinea-pig hypogastric ganglion, since responses to preganglionic nerve trunk stimulation were lost no sooner than responses to postganglionic nerve trunk stimulation. 2. The responses to postganglionic nerve trunk stimulation were blocked by vinblastine or vincristine at a time when responses to stimulation of intramural nerve fibres were little affected. 3. The results do not support the suggestion that inhibition of the exocytotic release of transmitter is responsible for the early in vitro effects of these drugs.", "contents": "The in vitro effects of vinblastine and vincristine on the responses of the guinea-pig vas deferens to nerve stimulation. 1. Neither vinblastine nor vincristine (1x10-4M) appeared to cause a specific blockade of transmission through the guinea-pig hypogastric ganglion, since responses to preganglionic nerve trunk stimulation were lost no sooner than responses to postganglionic nerve trunk stimulation. 2. The responses to postganglionic nerve trunk stimulation were blocked by vinblastine or vincristine at a time when responses to stimulation of intramural nerve fibres were little affected. 3. The results do not support the suggestion that inhibition of the exocytotic release of transmitter is responsible for the early in vitro effects of these drugs."} {"id": "PMID:167317", "title": "Ultrastructural changes accompanying the induced differentiation of clonal rat nerve and glia.", "content": "Dibutyryladenosine 3'-5' monophosphate (DBcAMP) induces ultrastructural transformations in clonal rat nerve and glia. Cells cultured in the presence of DBcAMP contain large numbers of aligned microtubules and microfilaments in their elongated processes, while control cultures without DBcAMP are relatively devoid of these structures. In addition, the cells exposed to DBcAMP contain 2000 A to 6000 A vesicles which are not observed in control cells.", "contents": "Ultrastructural changes accompanying the induced differentiation of clonal rat nerve and glia. Dibutyryladenosine 3'-5' monophosphate (DBcAMP) induces ultrastructural transformations in clonal rat nerve and glia. Cells cultured in the presence of DBcAMP contain large numbers of aligned microtubules and microfilaments in their elongated processes, while control cultures without DBcAMP are relatively devoid of these structures. In addition, the cells exposed to DBcAMP contain 2000 A to 6000 A vesicles which are not observed in control cells."} {"id": "PMID:167318", "title": "Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. I. Analysis of amino acids at maximum of potentiation.", "content": "In order to determine the chemical changes which might occur during post-tetanic potentiation, amino acids from the motor regions of the ventral horn of the spinal cord (potentiated and unpotentiated sides) of 10 different cats were analyzed. The intermittent tetanic stimulation of the Nn. gastroc. (only on the potentiated side) was carried out until a maximum of potentiation was reached (3--4 min). The monosynaptic reflexes were obtained from the ventral roots (L7 or S1) of both sides. The amino acids of the potentiated side were compared to those of the unpotentiated side (control) using a 14-C-dansyl chloride procedure. The two main amino acids considered to be excitatory neurotransmitters, glutamic acid and aspartic acid, showed a more than 20 per cent increase on the potentiated side as compared to the control side. Glycine, which plays an inhibitory role, especially in the spinal cord, reacted with 6 per cent decrease, whereas GABA which is also considered as an inhibitory neurotransmitter showed a change of + 11 per cent on the potentiated side as compared to the unpotentiated side. The importance of the potentiation time for those changes is pointed out.", "contents": "Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. I. Analysis of amino acids at maximum of potentiation. In order to determine the chemical changes which might occur during post-tetanic potentiation, amino acids from the motor regions of the ventral horn of the spinal cord (potentiated and unpotentiated sides) of 10 different cats were analyzed. The intermittent tetanic stimulation of the Nn. gastroc. (only on the potentiated side) was carried out until a maximum of potentiation was reached (3--4 min). The monosynaptic reflexes were obtained from the ventral roots (L7 or S1) of both sides. The amino acids of the potentiated side were compared to those of the unpotentiated side (control) using a 14-C-dansyl chloride procedure. The two main amino acids considered to be excitatory neurotransmitters, glutamic acid and aspartic acid, showed a more than 20 per cent increase on the potentiated side as compared to the control side. Glycine, which plays an inhibitory role, especially in the spinal cord, reacted with 6 per cent decrease, whereas GABA which is also considered as an inhibitory neurotransmitter showed a change of + 11 per cent on the potentiated side as compared to the unpotentiated side. The importance of the potentiation time for those changes is pointed out."} {"id": "PMID:167319", "title": "The effect of pentobarbital on basal and ether-stimulated ACTH secretion in intact and adrenalectomized rats.", "content": "Pentobarbital in a dose of 3.5 mg/100 g b.w. did not suppress the high basal a.m. levels of plasma ACTH in adrenalectomized male rats. In both intact and adrenalectomized rats prior administration of the drug slightly depressed the rise in plasma ACTH induced by 2.5 min of ether inhalation, but this depression is of questionable statistical significance.", "contents": "The effect of pentobarbital on basal and ether-stimulated ACTH secretion in intact and adrenalectomized rats. Pentobarbital in a dose of 3.5 mg/100 g b.w. did not suppress the high basal a.m. levels of plasma ACTH in adrenalectomized male rats. In both intact and adrenalectomized rats prior administration of the drug slightly depressed the rise in plasma ACTH induced by 2.5 min of ether inhalation, but this depression is of questionable statistical significance."} {"id": "PMID:167320", "title": "Growth hormone effects on sleep and wakefulness in the rat.", "content": "The sleep-wakefulness pattern and brain protein levels were determined in rats for 3 h following these conditions: administration of an inhibitor of protein synthesis (anisomycin), administration of several doses of rat growth hormone (GH) or thyrotropin, and administration of a combination of anisomycin + GH or thyrotropin. Anisomycin inhibited sleep and increased wakefulness, GH increased REM sleep, and thyrotropin produced no change. The combined administration of GH and anisomycin returned sleep to control levels. Anisomycin produced a time-dependent decrease in brain protein levels, GH produced changes in brain protein levels as compared to controls in the second hour only, and thyrotropin had no effect upon brain protein levels. The results are discussed in terms of the possible relationship between sleep and proteins.", "contents": "Growth hormone effects on sleep and wakefulness in the rat. The sleep-wakefulness pattern and brain protein levels were determined in rats for 3 h following these conditions: administration of an inhibitor of protein synthesis (anisomycin), administration of several doses of rat growth hormone (GH) or thyrotropin, and administration of a combination of anisomycin + GH or thyrotropin. Anisomycin inhibited sleep and increased wakefulness, GH increased REM sleep, and thyrotropin produced no change. The combined administration of GH and anisomycin returned sleep to control levels. Anisomycin produced a time-dependent decrease in brain protein levels, GH produced changes in brain protein levels as compared to controls in the second hour only, and thyrotropin had no effect upon brain protein levels. The results are discussed in terms of the possible relationship between sleep and proteins."} {"id": "PMID:167326", "title": "[Bilateral carcinoma of the breast].", "content": "Bilateral breast cancer is examined in the light of the literature data and a personal series. Lobular, asynchronous forms, either in situ or infiltrating, are usually involved. The fact that in situ changes are often found in the second neoplasia, with metastases solely in its tributary lymph nodes, suggests that such carcinoma was already present at the time of the first operation, though not clinically detectable. Since bilateral forms are commonly hormone-dependent, multiple biopsies should be routine on the contralateral breast. Preventive mastectomy associated with ovariectomy shold be performed on the slightest sign of carcinomatous or even precancerous alterations.", "contents": "[Bilateral carcinoma of the breast]. Bilateral breast cancer is examined in the light of the literature data and a personal series. Lobular, asynchronous forms, either in situ or infiltrating, are usually involved. The fact that in situ changes are often found in the second neoplasia, with metastases solely in its tributary lymph nodes, suggests that such carcinoma was already present at the time of the first operation, though not clinically detectable. Since bilateral forms are commonly hormone-dependent, multiple biopsies should be routine on the contralateral breast. Preventive mastectomy associated with ovariectomy shold be performed on the slightest sign of carcinomatous or even precancerous alterations."} {"id": "PMID:167334", "title": "Odontodysplasia. Report of two cases and review of the literature.", "content": "Odontodysplasia is a rare developmental anomaly affecting the tooth structures in both deciduous and permanent dentitions. The enamel is thin and uneven in thickness, and the detinal tissue surrounds very large pulp chambers. Denticles are present in the pulp organ. The maxilla is involved twice as frequently as the mandible. Most of the affected teeth are in the anterior segments; however, all other teeth can be affected. The cause is unknown. Because of the tendency of the affected teeth to develop abscesses, the most common treatment is extraction. Two additional cases are reported, and the literature is reviewed.", "contents": "Odontodysplasia. Report of two cases and review of the literature. Odontodysplasia is a rare developmental anomaly affecting the tooth structures in both deciduous and permanent dentitions. The enamel is thin and uneven in thickness, and the detinal tissue surrounds very large pulp chambers. Denticles are present in the pulp organ. The maxilla is involved twice as frequently as the mandible. Most of the affected teeth are in the anterior segments; however, all other teeth can be affected. The cause is unknown. Because of the tendency of the affected teeth to develop abscesses, the most common treatment is extraction. Two additional cases are reported, and the literature is reviewed."} {"id": "PMID:167342", "title": "[Changes in the muscle fiber induced by p-phenylenediamine in the rat].", "content": "P-phenylenediamine (PPD) induces skeletal muscle lesions in rats which have been chosen as a model for investigation of the inflammatory and degenerative pattern of the muscle fibers. With the use of histochemical and ultrastructural criteria, the morphology of the lesions have been analysed in the diaphragm. Fifteen minutes after the induction by PPD, a subsarclemmal oedema can be shown by electron microscopy. Enzymatic changes appear during the first hour. The pathologic features are more prominent after twenty-four hours. The lesions are characterized by a segmental necrosis adjacent to unaltered fibers and by particular types of fibers such as target, snake coils, core fiber. A comparison between the lesions induced by PPD and those occurring during other types of myopathies has been made.", "contents": "[Changes in the muscle fiber induced by p-phenylenediamine in the rat]. P-phenylenediamine (PPD) induces skeletal muscle lesions in rats which have been chosen as a model for investigation of the inflammatory and degenerative pattern of the muscle fibers. With the use of histochemical and ultrastructural criteria, the morphology of the lesions have been analysed in the diaphragm. Fifteen minutes after the induction by PPD, a subsarclemmal oedema can be shown by electron microscopy. Enzymatic changes appear during the first hour. The pathologic features are more prominent after twenty-four hours. The lesions are characterized by a segmental necrosis adjacent to unaltered fibers and by particular types of fibers such as target, snake coils, core fiber. A comparison between the lesions induced by PPD and those occurring during other types of myopathies has been made."} {"id": "PMID:167348", "title": "[Gram negative bacillus septicemias. Results of treatment of 31 gram negative bacillus septicemias using intravenous nalidixic acid].", "content": "Enterobacteria multiresistant to usual antibiotics, often remain sensitive to nalidixic acid, sometimes as a result of synergy with polymixins. Use of the intravenous route makes it possible to obtain more than adequate serum levels. Pharmacological study has indicated appropriate doses in terms of renal function. Intravenous nalidixic acid has been used in the treatment of 31 cases of Gram negative septicaemia, with success in 22. These results are all the more significant given that the patients were all seriously ill, cultures having grown multiresistant organisms and that nalidixic acid was used only after other antibiotics had failed.", "contents": "[Gram negative bacillus septicemias. Results of treatment of 31 gram negative bacillus septicemias using intravenous nalidixic acid]. Enterobacteria multiresistant to usual antibiotics, often remain sensitive to nalidixic acid, sometimes as a result of synergy with polymixins. Use of the intravenous route makes it possible to obtain more than adequate serum levels. Pharmacological study has indicated appropriate doses in terms of renal function. Intravenous nalidixic acid has been used in the treatment of 31 cases of Gram negative septicaemia, with success in 22. These results are all the more significant given that the patients were all seriously ill, cultures having grown multiresistant organisms and that nalidixic acid was used only after other antibiotics had failed."} {"id": "PMID:167349", "title": "Enzymatic synthesis of oligonucleotides of defined sequence. Addition of short blocks of nucleotide residues to oligonucleotide primers.", "content": "Polynucleotide phosphorylase from Escherichia coli can be used to catalyse the addition of short tracts of deoxyadenylate residues to the 3'-termini of deoxyribooligonucleotides of the type pdAn-dN (where dN = dC, dT or dG) using dADP as donor. Similarly, the enzyme can also be used to catalyse the addition of short tracts of adenylate residues to the 3'-termini of ribooligonucleotides of the type An-N (where N = C, U or G) using ADP as donor. In the ribooligonucleotide series, phosphorolytic cleavage of the primer oligonucleotides is significant and results in the concommitant production of oligoadenylates lacking the N residue. Oligomers of the same length, with and without the residue N, were readily separated by thermal elution from cellulose-pdT9 columns. This latter procedure therefore provides a simple method for purification of the oligoadenylates containing an internal base substitution and it also provides a convenient assay for oligonucleotide phosphorolysis.", "contents": "Enzymatic synthesis of oligonucleotides of defined sequence. Addition of short blocks of nucleotide residues to oligonucleotide primers. Polynucleotide phosphorylase from Escherichia coli can be used to catalyse the addition of short tracts of deoxyadenylate residues to the 3'-termini of deoxyribooligonucleotides of the type pdAn-dN (where dN = dC, dT or dG) using dADP as donor. Similarly, the enzyme can also be used to catalyse the addition of short tracts of adenylate residues to the 3'-termini of ribooligonucleotides of the type An-N (where N = C, U or G) using ADP as donor. In the ribooligonucleotide series, phosphorolytic cleavage of the primer oligonucleotides is significant and results in the concommitant production of oligoadenylates lacking the N residue. Oligomers of the same length, with and without the residue N, were readily separated by thermal elution from cellulose-pdT9 columns. This latter procedure therefore provides a simple method for purification of the oligoadenylates containing an internal base substitution and it also provides a convenient assay for oligonucleotide phosphorolysis."} {"id": "PMID:167350", "title": "Solid support synthesis of oligothymidylates using phosphorochloridates and 1-alkylimidazoles.", "content": "A study of the synthesis of oligothymidylates via phosphotriester intermediates on a polystyrene support is described. The sequence involves condensation of a phenyl nucleoside-3' -phosphorochloridate with the 5'-hydroxyl group of the carrier bound oligonucleotide derivative in the presence of 1-methylimidazole. Conditions for preparation of the phenyl nucleo-side phosphorochloridate as well as for the condensation on the support are discussed. d-TpTpTpT was obtained in 31% overall yield from carrier bound thymidine in one series of experiments, and d-TpTpTpTpT was obtained in 9% yield in another. The cycle for addition of one nucleotide unit can be completed in about six hours.", "contents": "Solid support synthesis of oligothymidylates using phosphorochloridates and 1-alkylimidazoles. A study of the synthesis of oligothymidylates via phosphotriester intermediates on a polystyrene support is described. The sequence involves condensation of a phenyl nucleoside-3' -phosphorochloridate with the 5'-hydroxyl group of the carrier bound oligonucleotide derivative in the presence of 1-methylimidazole. Conditions for preparation of the phenyl nucleo-side phosphorochloridate as well as for the condensation on the support are discussed. d-TpTpTpT was obtained in 31% overall yield from carrier bound thymidine in one series of experiments, and d-TpTpTpTpT was obtained in 9% yield in another. The cycle for addition of one nucleotide unit can be completed in about six hours."} {"id": "PMID:167351", "title": "The 3' terminal oligonucleotide of E. coli 16S ribosomal RNA: the sequence in both wild-type and RNase iii- cells is complementary to the polypurine tracts common to mRNA initiator regions.", "content": "Application of Sanger techniques to the analysis of the 3' terminal oligonucleotide from E. coli 32-P-labelled 16 S rRNA yields the sequence AUCACCUCCUUAOH. This sequence is identical in RNA isolated from two wild-type strains (MRE600 and E. coli B, SY106) and from a mutant strain (AB301/105) defective in RNase III. Data presented here explains the previous derivation of an incorrect sequence (AUCCUCACUUCAOH) by others. The functional significance of complementarity between the 3' terminus of 16S rRNA and poly-purine tracts commonly found in mRNA initiator regions is discussed.", "contents": "The 3' terminal oligonucleotide of E. coli 16S ribosomal RNA: the sequence in both wild-type and RNase iii- cells is complementary to the polypurine tracts common to mRNA initiator regions. Application of Sanger techniques to the analysis of the 3' terminal oligonucleotide from E. coli 32-P-labelled 16 S rRNA yields the sequence AUCACCUCCUUAOH. This sequence is identical in RNA isolated from two wild-type strains (MRE600 and E. coli B, SY106) and from a mutant strain (AB301/105) defective in RNase III. Data presented here explains the previous derivation of an incorrect sequence (AUCCUCACUUCAOH) by others. The functional significance of complementarity between the 3' terminus of 16S rRNA and poly-purine tracts commonly found in mRNA initiator regions is discussed."} {"id": "PMID:167352", "title": "Specifity of DNA-basic polypeptide interactions. Influence of neutral residues incorporated into polylysine and polyarginine.", "content": "An approach is described for evaluation of the specificity of basic polypeptides concerning the base pair composition of DNA. The polypeptides were covalently bound to CNBr activated agarose and two DNAs strongly different in base composition but of equal molecular weight were loaded and detached by a NaCl gradient. The difference in the NaCl concerntrations between the elution maxima of the two DNAs was taken as a measure for the recognition specificity. The results obtained confirmed the known AT- und GC-specificity of polylysine and polyarginine, respectively. Neutral residues incorporated into polylysine generally reduce the interaction affinity and also the AT-specificity of their host. This behavior is very pronounced with three homogeneous fractions of clupeine containing about one third of neutral aliphatic amino acids within clusters of arginine; the base pair specificity of these arginine copolymers was found to be practically nil.", "contents": "Specifity of DNA-basic polypeptide interactions. Influence of neutral residues incorporated into polylysine and polyarginine. An approach is described for evaluation of the specificity of basic polypeptides concerning the base pair composition of DNA. The polypeptides were covalently bound to CNBr activated agarose and two DNAs strongly different in base composition but of equal molecular weight were loaded and detached by a NaCl gradient. The difference in the NaCl concerntrations between the elution maxima of the two DNAs was taken as a measure for the recognition specificity. The results obtained confirmed the known AT- und GC-specificity of polylysine and polyarginine, respectively. Neutral residues incorporated into polylysine generally reduce the interaction affinity and also the AT-specificity of their host. This behavior is very pronounced with three homogeneous fractions of clupeine containing about one third of neutral aliphatic amino acids within clusters of arginine; the base pair specificity of these arginine copolymers was found to be practically nil."} {"id": "PMID:167353", "title": "Repair methylation of parental DNA in synchronized cultures of Novikoff hepatoma cells.", "content": "Parental and filial DNA strands were isolated from a Novikoff rat hepatoma cell line, synchronized by S-phase arrest with excess thymidine, that had completed up to one round of DNA replication in the presence of (14-C-methyl)methionine and (6-3-H) bromodeoxyuridine. Both strands were methylated, the proportion of total methyl label in parental DNA increasing slightly with time in S-phase. The studies were repeated with (14-C-methyl)methionine and (3-H)deoxycytidine to determine if parental methylation occurred on extant or repair-inserted cytosine residues. Both (14-C) and (3-H) were found in parental DNA. The (14-C)/(3-H) ration of parental DNA-5-methylcytosine was about twice that in filial DNA while the (3-H) data showed twice the concentration of 5-methylcytosine in parental compared to filial DNA. Thus parental methylation occurred on repair-inserted cytosine residues and resulted in overmethylation. That the DNA damage and repair was due to 5-phase arrest was shown by repeating the studies using a sequential mitotic-G1 arrest method. With this method little (14-C) or (3-H) was found in parental DNA. We conclude that S-phase arrest leads to DNA damage and repair with subsequent overmethylation of repair-inserted cytosines; that sequential mitotic-G1 arrest minimizes DNA damage; and, that the latter technique, suitable for synchronization of large quantities of cells, may prove useful in relatively artifact-free studies of eukaryotic DNA replication.", "contents": "Repair methylation of parental DNA in synchronized cultures of Novikoff hepatoma cells. Parental and filial DNA strands were isolated from a Novikoff rat hepatoma cell line, synchronized by S-phase arrest with excess thymidine, that had completed up to one round of DNA replication in the presence of (14-C-methyl)methionine and (6-3-H) bromodeoxyuridine. Both strands were methylated, the proportion of total methyl label in parental DNA increasing slightly with time in S-phase. The studies were repeated with (14-C-methyl)methionine and (3-H)deoxycytidine to determine if parental methylation occurred on extant or repair-inserted cytosine residues. Both (14-C) and (3-H) were found in parental DNA. The (14-C)/(3-H) ration of parental DNA-5-methylcytosine was about twice that in filial DNA while the (3-H) data showed twice the concentration of 5-methylcytosine in parental compared to filial DNA. Thus parental methylation occurred on repair-inserted cytosine residues and resulted in overmethylation. That the DNA damage and repair was due to 5-phase arrest was shown by repeating the studies using a sequential mitotic-G1 arrest method. With this method little (14-C) or (3-H) was found in parental DNA. We conclude that S-phase arrest leads to DNA damage and repair with subsequent overmethylation of repair-inserted cytosines; that sequential mitotic-G1 arrest minimizes DNA damage; and, that the latter technique, suitable for synchronization of large quantities of cells, may prove useful in relatively artifact-free studies of eukaryotic DNA replication."} {"id": "PMID:167354", "title": "Determination of the sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 DNA.", "content": "The sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 bacteriophage DNA have been determined to be pT-C-T-C-A-C-A-G-T-G-T-A-C-G-T-C-C-C (1-strand) and pA-G-G-G-A-C-A-C-A-G-C-G-C-T-C (r-strand). The 5'-termini of whole DNA or separated strands were kinased using polynucleotide kinase and (gamma-32-P) rATP. The DNA was partially digested with pancreatic DNase and the fragments were separated by two dimensional electrophoresis and homochromatography. To complete the sequence, snake venom phosphodiesterase digestions of these fragments were carried out. The relationship of these sequences to the proposed cleavage of concatemeric DNA during DNA replication is discussed.", "contents": "Determination of the sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 DNA. The sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 bacteriophage DNA have been determined to be pT-C-T-C-A-C-A-G-T-G-T-A-C-G-T-C-C-C (1-strand) and pA-G-G-G-A-C-A-C-A-G-C-G-C-T-C (r-strand). The 5'-termini of whole DNA or separated strands were kinased using polynucleotide kinase and (gamma-32-P) rATP. The DNA was partially digested with pancreatic DNase and the fragments were separated by two dimensional electrophoresis and homochromatography. To complete the sequence, snake venom phosphodiesterase digestions of these fragments were carried out. The relationship of these sequences to the proposed cleavage of concatemeric DNA during DNA replication is discussed."} {"id": "PMID:167355", "title": "The determination of secondary structure in the poly(C) tract of encephalomyocarditis virus RNA with sodium bisulphite.", "content": "The degree of secondary structure in the poly(C) tract of encephalomyocarditis virus (EMCV) RNA has been investigated using sodium bisulphite, which brings about the hydrolysis of non-base-paired cytidylic acid to uridylic acid in RNA. The percentage conversion of C to U in the poly(C) region of native EMCV RNA was similar to that found in a synthetic polynucleotide lacking secondary structure [poly(C)]. When poly(I) was annealed to either native or denatured EMCV RNA, it protected the poly(C) tract from the action of bisulphite. It is concluded that the poly(C) tract of EMCV RNA in solution is very largely single-stranded.", "contents": "The determination of secondary structure in the poly(C) tract of encephalomyocarditis virus RNA with sodium bisulphite. The degree of secondary structure in the poly(C) tract of encephalomyocarditis virus (EMCV) RNA has been investigated using sodium bisulphite, which brings about the hydrolysis of non-base-paired cytidylic acid to uridylic acid in RNA. The percentage conversion of C to U in the poly(C) region of native EMCV RNA was similar to that found in a synthetic polynucleotide lacking secondary structure [poly(C)]. When poly(I) was annealed to either native or denatured EMCV RNA, it protected the poly(C) tract from the action of bisulphite. It is concluded that the poly(C) tract of EMCV RNA in solution is very largely single-stranded."} {"id": "PMID:167356", "title": "Differentiation between exonucleases and endonucleases and between haplotomic and diplotomic endonucleases using 3-h-dna-coated wells of plastic depression plates as substrate.", "content": "Using our new method for assaying DNases with radioactively labeled DNA bound to wells of plastic depression plates as substrate, we could distinguish between endonucleases and exonucleases and between haplotomic and diplotomic endonucleases. Oligonucleotides smaller than 30 detach from the DNA binding sites of the well into the reaction mixture. Thus, a lag period was evident before endonucleases produced small soluble oligonucleotides, while exonucleases released mononucleotides or short oligonucleotides without any lag period. Haplotomic and diplotomic endonucleases were detected because of the different rates in which they produce small soluble oligonucleotides which were expressed in different lag periods. Under conditions in which the haplotomic DNase 1 changes its mode of action to become a diplotomic enzyme, the shift was clearly detected by a change in the lag period in the well assay.", "contents": "Differentiation between exonucleases and endonucleases and between haplotomic and diplotomic endonucleases using 3-h-dna-coated wells of plastic depression plates as substrate. Using our new method for assaying DNases with radioactively labeled DNA bound to wells of plastic depression plates as substrate, we could distinguish between endonucleases and exonucleases and between haplotomic and diplotomic endonucleases. Oligonucleotides smaller than 30 detach from the DNA binding sites of the well into the reaction mixture. Thus, a lag period was evident before endonucleases produced small soluble oligonucleotides, while exonucleases released mononucleotides or short oligonucleotides without any lag period. Haplotomic and diplotomic endonucleases were detected because of the different rates in which they produce small soluble oligonucleotides which were expressed in different lag periods. Under conditions in which the haplotomic DNase 1 changes its mode of action to become a diplotomic enzyme, the shift was clearly detected by a change in the lag period in the well assay."} {"id": "PMID:167357", "title": "The modified nucleosides of tRNAs. II. Synthesis of 2'-O-methylcytidylyl (3'-5') cytidine.", "content": "The synthesis of 2'-O-methylcytidylyl (3'-5')cytidine by the triester method using as protecting groups, 2,2,2-trichloroethyl for phosphate hydroxyl group, p-chlorophenyoxyacetyl for 5-hydroxyl group, methoxymethylidene for 2',3'-cis-diol system, and benzoyl for the exo-amino group of cytidine is presented. The obtained product was characterised by UV, electrophoresis, chromatography and an enzymatic digestion.", "contents": "The modified nucleosides of tRNAs. II. Synthesis of 2'-O-methylcytidylyl (3'-5') cytidine. The synthesis of 2'-O-methylcytidylyl (3'-5')cytidine by the triester method using as protecting groups, 2,2,2-trichloroethyl for phosphate hydroxyl group, p-chlorophenyoxyacetyl for 5-hydroxyl group, methoxymethylidene for 2',3'-cis-diol system, and benzoyl for the exo-amino group of cytidine is presented. The obtained product was characterised by UV, electrophoresis, chromatography and an enzymatic digestion."} {"id": "PMID:167365", "title": "Structural and compositional changes attending the ultracentrifugation of very low density lipoproteins.", "content": "The effects of repetitive ultracentrifugation on the physical and chemical properties of very low density lipoproteins (VLDL) were investigated. VLDL recentrifuged one to seven times were characterized by chemical analyses, analytical ultracentrifugation and electron microscopy. The VLDL content of triglyceride was increased and the proportion of phospholipid decreased by ultracentrifugation. Recentrifugation of VLDL decreased the number of Sf-o 20-100 particles and generated particles of Sf-o greater than 400. The bulk of the material removed from VLDL by ultracentrifugation was lipoprotein having pre-beta mobility on paper electrophoresis, flotation rates of Sf-o 10-100 and a particle size of 300-400 A-O. Two ultracentrifugations separated an average of 14% of the starting VLDL protein. Characterization of the apoproteins in this material by polyacrylamide gel electrophoresis, gel chromatography, immunoprecipitation and amino acid analysis demonstrated a relatively high proportion of beta-apoprotein and relatively little C-apoproteins.", "contents": "Structural and compositional changes attending the ultracentrifugation of very low density lipoproteins. The effects of repetitive ultracentrifugation on the physical and chemical properties of very low density lipoproteins (VLDL) were investigated. VLDL recentrifuged one to seven times were characterized by chemical analyses, analytical ultracentrifugation and electron microscopy. The VLDL content of triglyceride was increased and the proportion of phospholipid decreased by ultracentrifugation. Recentrifugation of VLDL decreased the number of Sf-o 20-100 particles and generated particles of Sf-o greater than 400. The bulk of the material removed from VLDL by ultracentrifugation was lipoprotein having pre-beta mobility on paper electrophoresis, flotation rates of Sf-o 10-100 and a particle size of 300-400 A-O. Two ultracentrifugations separated an average of 14% of the starting VLDL protein. Characterization of the apoproteins in this material by polyacrylamide gel electrophoresis, gel chromatography, immunoprecipitation and amino acid analysis demonstrated a relatively high proportion of beta-apoprotein and relatively little C-apoproteins."} {"id": "PMID:167364", "title": "[Carcinoma of the breast in the male. Clinicopathological study of 10 cases].", "content": "The carcinoma of the male breast is a rare lesion, being aproximatelly 100 times less frequent than in women. Of 1930 cases of mammary cancer seen at the Hospital of Oncology of the National Medical Center, I.M.S.S. during a period of 10 years we found 10 histologically proved cases of carcinoma of the male breast. Their microscopic appearence was that of an invasive ductal carcinoma. The surgical treatment consisted in radical mastectomy on six patients, supermastectomy is one case and simple mastectomy in other. Two patients received radio and chemotherapy. In three patients bilateral orchiectomy was done and in other two cases a bilateral adrenalectomy was performed. The results of the review of these cases are compared with other previously reported.", "contents": "[Carcinoma of the breast in the male. Clinicopathological study of 10 cases]. The carcinoma of the male breast is a rare lesion, being aproximatelly 100 times less frequent than in women. Of 1930 cases of mammary cancer seen at the Hospital of Oncology of the National Medical Center, I.M.S.S. during a period of 10 years we found 10 histologically proved cases of carcinoma of the male breast. Their microscopic appearence was that of an invasive ductal carcinoma. The surgical treatment consisted in radical mastectomy on six patients, supermastectomy is one case and simple mastectomy in other. Two patients received radio and chemotherapy. In three patients bilateral orchiectomy was done and in other two cases a bilateral adrenalectomy was performed. The results of the review of these cases are compared with other previously reported."} {"id": "PMID:167368", "title": "[Experience in the use of competitive binding of hormones with proteins for the determination of non-metabolized glucocorticoids in the blood and urine in some pituitary-adrenal diseases].", "content": "A method of competitive protein-binding analysis was applied to the study of nonmetabolized glucocorticoids (NMG) in the plasma and urine of healthy persons and those suffering from hyper- and hypocorticism. NMG determination by this method reflected adequately the funcitonal condition of the adrenal cortex under normal conditions and in hypophyseo-adrenal diseases, including tests with ACTH and dexametazan, and coordinated with the results obtained by standard chemical methods.", "contents": "[Experience in the use of competitive binding of hormones with proteins for the determination of non-metabolized glucocorticoids in the blood and urine in some pituitary-adrenal diseases]. A method of competitive protein-binding analysis was applied to the study of nonmetabolized glucocorticoids (NMG) in the plasma and urine of healthy persons and those suffering from hyper- and hypocorticism. NMG determination by this method reflected adequately the funcitonal condition of the adrenal cortex under normal conditions and in hypophyseo-adrenal diseases, including tests with ACTH and dexametazan, and coordinated with the results obtained by standard chemical methods."} {"id": "PMID:167373", "title": "Serum prolactin levels and prolactin binding activity in adrenals and kidneys of male rats after dehydration, salt loading, and unilateral nephrectomy.", "content": "Serum prolactin (PRL) levels and PRL binding activity in microsomal membranes from kidneys and adrenals were measured in control, water-deprived, unilaterally nephrectomized, and salt-loaded male rats. Unilateral nephrectomy and water deprivation increased serum prolactin levels significantly. Unilateral nephrectomy did not alter PRL binding activity in the kidneys, but significantly increased it in the adrenal glands. Salt loading had no effect on serum prolactin levels or PRL binding in the kidneys; but significantly increased PRL binding in the adrenal glands. Inhibition curves and tests of cross reactivity with LH, FSH, TSH, and GH showed that binding of PRL to its receptors in the kidneys and adrenals was specific. These observations suggest that PRL has a role in salt and water metabolism and that PRL receptors in the kidney and adrenals participate in this regulatory system.", "contents": "Serum prolactin levels and prolactin binding activity in adrenals and kidneys of male rats after dehydration, salt loading, and unilateral nephrectomy. Serum prolactin (PRL) levels and PRL binding activity in microsomal membranes from kidneys and adrenals were measured in control, water-deprived, unilaterally nephrectomized, and salt-loaded male rats. Unilateral nephrectomy and water deprivation increased serum prolactin levels significantly. Unilateral nephrectomy did not alter PRL binding activity in the kidneys, but significantly increased it in the adrenal glands. Salt loading had no effect on serum prolactin levels or PRL binding in the kidneys; but significantly increased PRL binding in the adrenal glands. Inhibition curves and tests of cross reactivity with LH, FSH, TSH, and GH showed that binding of PRL to its receptors in the kidneys and adrenals was specific. These observations suggest that PRL has a role in salt and water metabolism and that PRL receptors in the kidney and adrenals participate in this regulatory system."} {"id": "PMID:167374", "title": "Inhibition by levamisole of metastases by cells transformed by herpes simplex virus type I.", "content": "Levamisole was tested to determine whether the drug could reduce metastases by HSV-1-transformed cells in a model hamster system. The results presented reveal an inhibition of metastases to the lungs even when the drug is inoculated after development of subcutaneous tumors at the site of inoculation of the cells.", "contents": "Inhibition by levamisole of metastases by cells transformed by herpes simplex virus type I. Levamisole was tested to determine whether the drug could reduce metastases by HSV-1-transformed cells in a model hamster system. The results presented reveal an inhibition of metastases to the lungs even when the drug is inoculated after development of subcutaneous tumors at the site of inoculation of the cells."} {"id": "PMID:167369", "title": "[Estradiol receptors in the sex organs and some other organs of male rats].", "content": "A study was made of specific binding of estradiol (E2) by cytosol and the extracts of the nuclei of the testes, the prostate, the kidneys and the liver of the sexually-mature male rats. In the cytosol of all the mentioned organs there were found macromolecules with a high affinity (Kac similar 1--4-10(9)M(-1)). Low capacity ti the hormone (Nc similar to (1--2)--minus 14 mol per 1 mg of protein) and a marked hormonal sterospecificity--only the preparations with an estrogenic activity, but not testosterone, 5alpha-dihydrotestosterone, progesterone and corticosterone competed for H-3--E2 binding. The capacity of cytosol of these organs to bind E2 apecifically was eliminated by pronase, but not by RNA-ase and DNA-ase. The mentioned properties of the E2-binding macromolecules of cytosol of the testes, the prostate, the kidneys and the liver permitted to refer them to the estrogenic protein-receptors. Specific E2-binding was also revealed in the extracts of the nuclei of these organs, but its level was extremely low.", "contents": "[Estradiol receptors in the sex organs and some other organs of male rats]. A study was made of specific binding of estradiol (E2) by cytosol and the extracts of the nuclei of the testes, the prostate, the kidneys and the liver of the sexually-mature male rats. In the cytosol of all the mentioned organs there were found macromolecules with a high affinity (Kac similar 1--4-10(9)M(-1)). Low capacity ti the hormone (Nc similar to (1--2)--minus 14 mol per 1 mg of protein) and a marked hormonal sterospecificity--only the preparations with an estrogenic activity, but not testosterone, 5alpha-dihydrotestosterone, progesterone and corticosterone competed for H-3--E2 binding. The capacity of cytosol of these organs to bind E2 apecifically was eliminated by pronase, but not by RNA-ase and DNA-ase. The mentioned properties of the E2-binding macromolecules of cytosol of the testes, the prostate, the kidneys and the liver permitted to refer them to the estrogenic protein-receptors. Specific E2-binding was also revealed in the extracts of the nuclei of these organs, but its level was extremely low."} {"id": "PMID:167375", "title": "Follicle stimulating hormone stimulation of 125-I-human chorionic gonadotropin binding in porcine granulosa cell cultures.", "content": "In order to see if FSH acts directly upon the granulosa cell to stimulate hCG binding, granulosa cells harvested from small 1-2 mm porcine follicles were grown in 250 ml flasks in chemically defined media containing 0.05 mug/ml highly purified human FSH for 2, 4, and 6 days. The defined medium consisted of culture medium 199 plus 0.4% bovine serum albumin, 0.2% lactalbumin hydrolysate and 10 munit/ml insulin. The cultures were harvested by scraping with a rubber policeman and incubated with 0.1 mug/ml 131-I- or 125-I-hCG. Binding expressed as cpm/culture or per mg protein yielded similar results. In five separate experiments addition of FSH stimulated hCG binding two- to fourfold above control cultures. In a typical experiment after 2 days of culture, the specific binding of control cultures to hCG was 962 plus or minus 45 cpm/culture (-x plus or minus SE; n = 3) and the binding in cultures grown in the presence of 0.05 mug/ml FSH was 3933 plus or minus 1787 (n = 3; P less than 0.01). Granulosa cells harvested from large (8-12 mm) follicles grown under similar conditions bound 29,669 plus or minus 948 cpm/culture (n = 4). These data demonstrate that FSH may have a direct stimulatory role upon induction of granulosa cell LH-hCG receptors in vitro.", "contents": "Follicle stimulating hormone stimulation of 125-I-human chorionic gonadotropin binding in porcine granulosa cell cultures. In order to see if FSH acts directly upon the granulosa cell to stimulate hCG binding, granulosa cells harvested from small 1-2 mm porcine follicles were grown in 250 ml flasks in chemically defined media containing 0.05 mug/ml highly purified human FSH for 2, 4, and 6 days. The defined medium consisted of culture medium 199 plus 0.4% bovine serum albumin, 0.2% lactalbumin hydrolysate and 10 munit/ml insulin. The cultures were harvested by scraping with a rubber policeman and incubated with 0.1 mug/ml 131-I- or 125-I-hCG. Binding expressed as cpm/culture or per mg protein yielded similar results. In five separate experiments addition of FSH stimulated hCG binding two- to fourfold above control cultures. In a typical experiment after 2 days of culture, the specific binding of control cultures to hCG was 962 plus or minus 45 cpm/culture (-x plus or minus SE; n = 3) and the binding in cultures grown in the presence of 0.05 mug/ml FSH was 3933 plus or minus 1787 (n = 3; P less than 0.01). Granulosa cells harvested from large (8-12 mm) follicles grown under similar conditions bound 29,669 plus or minus 948 cpm/culture (n = 4). These data demonstrate that FSH may have a direct stimulatory role upon induction of granulosa cell LH-hCG receptors in vitro."} {"id": "PMID:167371", "title": "[Reactivity of the adrenals to ACTH in rats with alloxan diabetes].", "content": "Experiments were conducted on rats. A study was made of the adrenal gland ACTH reactivity under conditions of alloxan diabetes. The function of the adrenal gland increased one month after the administration of alloxan; this was indicated by an increase of their absolute and relative weight, by an elevation of the corticosterone content in the peripheral blood and the glands proper. ACTH stimulated the adrenal gland function in rats with an intact pancreas, increasing the weight of the adrenal glands, the level of corticosterones in the blood and the adrenal glands. ACTH reactivity proved to be lowered in rats with alloxan diabetes. The blood corticosterone level increased in them less and changes in the weight of the glands and of the hormone concentration in them proved to be statistically insignificant.", "contents": "[Reactivity of the adrenals to ACTH in rats with alloxan diabetes]. Experiments were conducted on rats. A study was made of the adrenal gland ACTH reactivity under conditions of alloxan diabetes. The function of the adrenal gland increased one month after the administration of alloxan; this was indicated by an increase of their absolute and relative weight, by an elevation of the corticosterone content in the peripheral blood and the glands proper. ACTH stimulated the adrenal gland function in rats with an intact pancreas, increasing the weight of the adrenal glands, the level of corticosterones in the blood and the adrenal glands. ACTH reactivity proved to be lowered in rats with alloxan diabetes. The blood corticosterone level increased in them less and changes in the weight of the glands and of the hormone concentration in them proved to be statistically insignificant."} {"id": "PMID:167370", "title": "[Effect of ACTH, TTH, and STH on respiration and oxidative phosphorylation in the liver of hypophysectomized rats].", "content": "An experimental study was make of the changes in respiration and of the oxidative phosphorylation in the hepatic mitochondria of the hypophysectomized albino rats, with consideration to the regulatory effects of the ACTH, TTH, and STH. There was an intensification of the conjugation of the oxidative and of the phosphorylation processes in the mitochondria of the liver of hypophysectomized albino rats as a result of ACTH replacement therapy in a dose of 3 Units per 100 g of weight. TTH given in a dose of 0.03 IU per 100 g of weight under conditions of hypophysectomy stimulated oxidation of alpha-ketoglutaric acid in the mitochondria of the liver of albino rats; phosphorylation remained reduced, i.e. there was seen a dissociation of the process of oxidative phosphorylation. As a result of replacement therapy with the STH given in a dose of 10 gamma per 100 g of weight the energy metabolism in the liver of hypophysectomized albino rats changed in the direction of an increase in the P/O coefficient of the hepatic mitochondria. ACTH, TTH, and STH were given from the 15th to the 21st days after hypophysectomy, twice a day, subcutaneously.", "contents": "[Effect of ACTH, TTH, and STH on respiration and oxidative phosphorylation in the liver of hypophysectomized rats]. An experimental study was make of the changes in respiration and of the oxidative phosphorylation in the hepatic mitochondria of the hypophysectomized albino rats, with consideration to the regulatory effects of the ACTH, TTH, and STH. There was an intensification of the conjugation of the oxidative and of the phosphorylation processes in the mitochondria of the liver of hypophysectomized albino rats as a result of ACTH replacement therapy in a dose of 3 Units per 100 g of weight. TTH given in a dose of 0.03 IU per 100 g of weight under conditions of hypophysectomy stimulated oxidation of alpha-ketoglutaric acid in the mitochondria of the liver of albino rats; phosphorylation remained reduced, i.e. there was seen a dissociation of the process of oxidative phosphorylation. As a result of replacement therapy with the STH given in a dose of 10 gamma per 100 g of weight the energy metabolism in the liver of hypophysectomized albino rats changed in the direction of an increase in the P/O coefficient of the hepatic mitochondria. ACTH, TTH, and STH were given from the 15th to the 21st days after hypophysectomy, twice a day, subcutaneously."} {"id": "PMID:167376", "title": "Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations.", "content": "A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.", "contents": "Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations. A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000."} {"id": "PMID:167377", "title": "Inhibitory effect of prolactin on the development of fatty liver induced by ACTH in thrat.", "content": "The action and interaction of ACTH and prolactin in the development of fatty liver were investigated in intact rats treated with exogenous hormones. Administration of ACTH or of combinations of ACTH and GH to intact female rats was found to elicit significantly greater increase in liver total lipids content and concentration than administration of combinations of ACTH, or ACTH and GH, with prolactin. In addition, the results support the data reported by Bates et al. (6) that simultaneous application of GH, prolactin and ACTH reduces the effct of ACTH, upon adrenal gland weight.", "contents": "Inhibitory effect of prolactin on the development of fatty liver induced by ACTH in thrat. The action and interaction of ACTH and prolactin in the development of fatty liver were investigated in intact rats treated with exogenous hormones. Administration of ACTH or of combinations of ACTH and GH to intact female rats was found to elicit significantly greater increase in liver total lipids content and concentration than administration of combinations of ACTH, or ACTH and GH, with prolactin. In addition, the results support the data reported by Bates et al. (6) that simultaneous application of GH, prolactin and ACTH reduces the effct of ACTH, upon adrenal gland weight."} {"id": "PMID:167378", "title": "Protection of A/He mice by a Friend virus pseudotype against challenge with Friend virus.", "content": "Prior inoculation of 7-wk-old A/He mice with the Graffi pseudotype of Friend virus protected the animals against subsequent challenge with Friend virus. Graffi leukemia virus itself did not induce protection, probably because it failed to replicate in these mice.", "contents": "Protection of A/He mice by a Friend virus pseudotype against challenge with Friend virus. Prior inoculation of 7-wk-old A/He mice with the Graffi pseudotype of Friend virus protected the animals against subsequent challenge with Friend virus. Graffi leukemia virus itself did not induce protection, probably because it failed to replicate in these mice."} {"id": "PMID:167379", "title": "Rubella and rheumatoid arthritis: hyaluronic acid and susceptibility of cultured rheumatoid synovial cells to viruses.", "content": "Synovial cell lines were established from patients with rheumatoid arthritis (RA) and from normal human embryos. High levels of hyaluronic acid (HA) were produced by some RA cell lines, some of which were partially or completely resistant to infection with Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and rubella virus (RV). Normal fetal synovial cells lines were susceptible to NDV, VSV, and RV. Infection with virus became possible after treatment of RA cells with hyaluronidase to depolymerize HA, and HA prevented infection of normal synovial cells with VSV. These results provide evidence that HA and not chronic or latent viral infection is responsible for the lack of susceptibility of RA synovial cells to certain viruses.", "contents": "Rubella and rheumatoid arthritis: hyaluronic acid and susceptibility of cultured rheumatoid synovial cells to viruses. Synovial cell lines were established from patients with rheumatoid arthritis (RA) and from normal human embryos. High levels of hyaluronic acid (HA) were produced by some RA cell lines, some of which were partially or completely resistant to infection with Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and rubella virus (RV). Normal fetal synovial cells lines were susceptible to NDV, VSV, and RV. Infection with virus became possible after treatment of RA cells with hyaluronidase to depolymerize HA, and HA prevented infection of normal synovial cells with VSV. These results provide evidence that HA and not chronic or latent viral infection is responsible for the lack of susceptibility of RA synovial cells to certain viruses."} {"id": "PMID:167380", "title": "Specific adenosine binding proteins from rat liver.", "content": "Specific adenosine-binding proteins from homogenates of rat liver have been fractionated on a DEAE-cellulose column. Three major peaks have been identified with respect to histone phosphokinase and cAMP and adenosine-binding activities. Peak I contains only histone phosphokinase activity not stimulated by cAMP. Peak II contains histone phosphokinase slightly stimulated by cAMP. Both cAMP- and adenosine-binding activities are found in this fraction. The major adenosine-binding protein is associated with Peak III. Histone phosphokinase in Peak III which also binds cAMP is stimulated 2-fold by 2.5 muM cAMP whereas adenosine at 2.5 X 10(-4)M inhibits these enzymes equally well in each of three peaks. The specificity of adenosine binding is discussed.", "contents": "Specific adenosine binding proteins from rat liver. Specific adenosine-binding proteins from homogenates of rat liver have been fractionated on a DEAE-cellulose column. Three major peaks have been identified with respect to histone phosphokinase and cAMP and adenosine-binding activities. Peak I contains only histone phosphokinase activity not stimulated by cAMP. Peak II contains histone phosphokinase slightly stimulated by cAMP. Both cAMP- and adenosine-binding activities are found in this fraction. The major adenosine-binding protein is associated with Peak III. Histone phosphokinase in Peak III which also binds cAMP is stimulated 2-fold by 2.5 muM cAMP whereas adenosine at 2.5 X 10(-4)M inhibits these enzymes equally well in each of three peaks. The specificity of adenosine binding is discussed."} {"id": "PMID:167381", "title": "Differences and similarities between guanosine 3',5'-cyclic monophosphate phosphodiesterase and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in neuroblastoma cells in culture.", "content": "There are phosphodiesterase activities in both particulate and supernatant fractions which hydrolyze guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) with an apparent Km of 2-8 muM and with an apparent Km of 44-222 muM. 4-(3-Butoxy-4-methoxybenzyl-2-imidazolidinone (RO20-1724) did not inhibit cGMP phosphodiesterase activity in homogenates of mouse neuroblastoma cells, but markedly inhibited cAMP phosphodiesterase activity. Papaverine and theophylline inhibited both cGMP and cAMP phosphodiesterase activities to about the same extent. The former was more potent than the latter. The specific activity of cGMP phosphodiesterase as a function of protein concentrations first increased and then decreased. The specific activity of cAMP phosphodiesterase decreased under a similar experimental condition.", "contents": "Differences and similarities between guanosine 3',5'-cyclic monophosphate phosphodiesterase and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in neuroblastoma cells in culture. There are phosphodiesterase activities in both particulate and supernatant fractions which hydrolyze guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) with an apparent Km of 2-8 muM and with an apparent Km of 44-222 muM. 4-(3-Butoxy-4-methoxybenzyl-2-imidazolidinone (RO20-1724) did not inhibit cGMP phosphodiesterase activity in homogenates of mouse neuroblastoma cells, but markedly inhibited cAMP phosphodiesterase activity. Papaverine and theophylline inhibited both cGMP and cAMP phosphodiesterase activities to about the same extent. The former was more potent than the latter. The specific activity of cGMP phosphodiesterase as a function of protein concentrations first increased and then decreased. The specific activity of cAMP phosphodiesterase decreased under a similar experimental condition."} {"id": "PMID:167382", "title": "Quantitative histochemical study of a vitamin E analog on rat gastric cyclic AMP.", "content": "The vitamin E analog, 2,2,7,8-tetramethyl-5,6-orthoquinonechroman, unlike vitamin E itself, had been reported to be a potent inhibitor of beef liver cyclic AMP-PDE in vitro (about 3.5 times more inhibitory than theophylline under the same conditions). In this in vivo study, single intraperitoneal injections were given to fasted rats, 15 min before killing, of a solution of 20, and of a suspension of 130, mg analog/kg in 4% ethanol. No significant increases over the 4% ethanol control values in cyclic AMP levels were produced in any of the histological regions of the glandular stomach. However, injection of the 4% ethanol itself produced a rise of about 50% (peak value 4.1 pmoles/mg wet wt, 0.16 pmoles/mug protein-nitrogen) in the cyclic AMP concentrations in the parietal cell region and had no significant effect in any of the other histological zones where the concentrations were much lower.", "contents": "Quantitative histochemical study of a vitamin E analog on rat gastric cyclic AMP. The vitamin E analog, 2,2,7,8-tetramethyl-5,6-orthoquinonechroman, unlike vitamin E itself, had been reported to be a potent inhibitor of beef liver cyclic AMP-PDE in vitro (about 3.5 times more inhibitory than theophylline under the same conditions). In this in vivo study, single intraperitoneal injections were given to fasted rats, 15 min before killing, of a solution of 20, and of a suspension of 130, mg analog/kg in 4% ethanol. No significant increases over the 4% ethanol control values in cyclic AMP levels were produced in any of the histological regions of the glandular stomach. However, injection of the 4% ethanol itself produced a rise of about 50% (peak value 4.1 pmoles/mg wet wt, 0.16 pmoles/mug protein-nitrogen) in the cyclic AMP concentrations in the parietal cell region and had no significant effect in any of the other histological zones where the concentrations were much lower."} {"id": "PMID:167383", "title": "Concerning the relationship between protein synthesis and adenosine-3',5'-cyclic phosphate-stimulated steroidogenesis in isolated rat adrenal cells.", "content": "Inhibitors of protein synthesis decrease protein synthesis in isolated rat adrenal cells to a greater extent than they decrease adenosine-3',5'-cyclic phosphate (cyclic AMP)-stimulated steroidogenesis. At low concentrations of the inhibitors, varying degrees of recovery of the rate of steroidogenesis occurs with increasing time of incubation. As the concentration is increased, the time required to achieve any recovery of the rate of steroidogenesis increases and the extent of recovery decreases. The recovery also depends on the amount of cyclic AMP present. During the process of recovery the inhibition of protein synthesis continues in a linear manner. An explanation consistent with these data involves a rapidly turningover protein, the concentration of which is independent of the level of cyclic AMP present. However, the extent of transformation of this protein to an active form depends on the concentration of cyclic AMP.", "contents": "Concerning the relationship between protein synthesis and adenosine-3',5'-cyclic phosphate-stimulated steroidogenesis in isolated rat adrenal cells. Inhibitors of protein synthesis decrease protein synthesis in isolated rat adrenal cells to a greater extent than they decrease adenosine-3',5'-cyclic phosphate (cyclic AMP)-stimulated steroidogenesis. At low concentrations of the inhibitors, varying degrees of recovery of the rate of steroidogenesis occurs with increasing time of incubation. As the concentration is increased, the time required to achieve any recovery of the rate of steroidogenesis increases and the extent of recovery decreases. The recovery also depends on the amount of cyclic AMP present. During the process of recovery the inhibition of protein synthesis continues in a linear manner. An explanation consistent with these data involves a rapidly turningover protein, the concentration of which is independent of the level of cyclic AMP present. However, the extent of transformation of this protein to an active form depends on the concentration of cyclic AMP."} {"id": "PMID:167384", "title": "Effects of steroid hormones on replication of murine sarcoma virus in mouse embryo cultures.", "content": "The androgenic steroid hormone, testosterone, inhibited focus formation by the murine Moloney sarcoma virus in mouse embryo cells. The inhibition of focus formation was enhanced by cyclic AMP. Although focus formation was inhibited, there was no inhibition of viral replication. The glucogenic adrenal corticosteroids, cortisol and dexamethasone, and 17-beta-estradiol and progesterone did not affect focus formation by MuSV(M).", "contents": "Effects of steroid hormones on replication of murine sarcoma virus in mouse embryo cultures. The androgenic steroid hormone, testosterone, inhibited focus formation by the murine Moloney sarcoma virus in mouse embryo cells. The inhibition of focus formation was enhanced by cyclic AMP. Although focus formation was inhibited, there was no inhibition of viral replication. The glucogenic adrenal corticosteroids, cortisol and dexamethasone, and 17-beta-estradiol and progesterone did not affect focus formation by MuSV(M)."} {"id": "PMID:167389", "title": "The development of superficial infraslow potential oscillations of the brain in chick embryos.", "content": "The development of superficial infraslow potential oscillations (ISPO) of brain hemispheres, cerebellum and optic lobes was studied in chick embryos between day 9 and 21 of incubation. The ISPO were firstly registered in brain hemispheres at day 10 of incubation, i.e. 5 days before the onset of spontaneous EEG activity. The ISPO in 10-day-old embryos had an average frequency of 9.9 c/min and an amplitude of 0.14 mV. During further development till hatching the frequency decreased to 7.5 c/min and the amplitude increased to 1.39 mV. Similar ISPO with the same developmental trend were also registered from the surface of the cerebellum and optic lobes. Superficial ISPO were not synchronized either between both hemispheres or between different fields of the same hemisphere.", "contents": "The development of superficial infraslow potential oscillations of the brain in chick embryos. The development of superficial infraslow potential oscillations (ISPO) of brain hemispheres, cerebellum and optic lobes was studied in chick embryos between day 9 and 21 of incubation. The ISPO were firstly registered in brain hemispheres at day 10 of incubation, i.e. 5 days before the onset of spontaneous EEG activity. The ISPO in 10-day-old embryos had an average frequency of 9.9 c/min and an amplitude of 0.14 mV. During further development till hatching the frequency decreased to 7.5 c/min and the amplitude increased to 1.39 mV. Similar ISPO with the same developmental trend were also registered from the surface of the cerebellum and optic lobes. Superficial ISPO were not synchronized either between both hemispheres or between different fields of the same hemisphere."} {"id": "PMID:167390", "title": "Functional differentiation of splanchnic A delta fibres in relation to viscerosomatic reflexes.", "content": "The splanchnic afferent signal in the myelinated fibre spectrum was analysed in cats and its relationship to viscerosomatic reflex activity was studied. In addition to Abeta and Adelta components, a further elevation was observed in the sympathetic chain neurogram. According to the conduction rate (15 plus or minus 4 m/sec), it was caused by myelinated fibres 2-3 mu in diameter. The presence of this component at thoracic dorsal root level, or in the sympathetic chain in stimulation of the postganglionic part of the nerve trunk, confirmed the afferent nature of the observed activity. The threshold stimulus for these fibres, which were termed group Adelta2, was four times higher than for Abeta fibres. Correlation of the neurogram with evoked activity in the intercostal nerves confirmed the different functional role of group Adelta2 fibres. Adelta2 fibre activity evokes the early component of the two-component viscerosomatic discharge and Adelta2 fibre activity its later component. The authors discuss the functional significance of Adelta2 fibres, which probably mediate nociceptive information from the viscera.", "contents": "Functional differentiation of splanchnic A delta fibres in relation to viscerosomatic reflexes. The splanchnic afferent signal in the myelinated fibre spectrum was analysed in cats and its relationship to viscerosomatic reflex activity was studied. In addition to Abeta and Adelta components, a further elevation was observed in the sympathetic chain neurogram. According to the conduction rate (15 plus or minus 4 m/sec), it was caused by myelinated fibres 2-3 mu in diameter. The presence of this component at thoracic dorsal root level, or in the sympathetic chain in stimulation of the postganglionic part of the nerve trunk, confirmed the afferent nature of the observed activity. The threshold stimulus for these fibres, which were termed group Adelta2, was four times higher than for Abeta fibres. Correlation of the neurogram with evoked activity in the intercostal nerves confirmed the different functional role of group Adelta2 fibres. Adelta2 fibre activity evokes the early component of the two-component viscerosomatic discharge and Adelta2 fibre activity its later component. The authors discuss the functional significance of Adelta2 fibres, which probably mediate nociceptive information from the viscera."} {"id": "PMID:167391", "title": "Relationship between the activity of postsynaptic spinal cord elements and propriospinal and spino-bulbo-spinal reflexes.", "content": "The relationship between the activity of the lumbar spinal interneurones and propriospinal (PS) and spino-bulbo-spinal (SBS) efferent reflex responses evoked by somatic (muscle, skin) and splanchnic nerve stimulation was studied in chloralose-anaestetized adult cats. During stimulation of one somatic nerve, the postsynaptic cord elements could be divided into three groups, according to whether their activity was was synchronous with the PS component of the efferent discharge (PS group), with the SBS component (SBS group) or with both (PS-SBS-group). Group SBS and PS-SBS interneurones were localized in the ventral quadrant of the grey matter. On stimulation of different nerves, the same interneurone could in one case respond synchronously with the PS component of the efferent discharge and in another with the SBS component. The membrane of units which did not generate propagated spike potentials during PS or SBS reflex activity was hyperpolarized in this period, or failed to display changes characteristic for postsynaptic inhibition. Convergence of somatic and visceral afferentation was observed in all three groups of postsynaptic elements. In type PS-SBS and SBS units it was massive (occurring in 85% and 100% of the cases respectively). The results confirmed the intimacy of functional contact of PS and SBS systems activated by somatic and visceral afferents.", "contents": "Relationship between the activity of postsynaptic spinal cord elements and propriospinal and spino-bulbo-spinal reflexes. The relationship between the activity of the lumbar spinal interneurones and propriospinal (PS) and spino-bulbo-spinal (SBS) efferent reflex responses evoked by somatic (muscle, skin) and splanchnic nerve stimulation was studied in chloralose-anaestetized adult cats. During stimulation of one somatic nerve, the postsynaptic cord elements could be divided into three groups, according to whether their activity was was synchronous with the PS component of the efferent discharge (PS group), with the SBS component (SBS group) or with both (PS-SBS-group). Group SBS and PS-SBS interneurones were localized in the ventral quadrant of the grey matter. On stimulation of different nerves, the same interneurone could in one case respond synchronously with the PS component of the efferent discharge and in another with the SBS component. The membrane of units which did not generate propagated spike potentials during PS or SBS reflex activity was hyperpolarized in this period, or failed to display changes characteristic for postsynaptic inhibition. Convergence of somatic and visceral afferentation was observed in all three groups of postsynaptic elements. In type PS-SBS and SBS units it was massive (occurring in 85% and 100% of the cases respectively). The results confirmed the intimacy of functional contact of PS and SBS systems activated by somatic and visceral afferents."} {"id": "PMID:167392", "title": "Nonspecific collagenolytic activity of the femoral bone in immobilized rat extremities.", "content": "Nonspecific collagenolytic activity was studied in rat bones after immobilization. The left hind limb was immobilized by sectioning the sciatic nerve. Enzyme activity was determined by using synthetic pentapeptide substrate (Pz-Pro-Leu-Gly-Pro-D-Arg). After immobilization the activity of nonspecific collagenase increased and reached its maximum on the third day after the operation. The activity was decreased after one week and attained levels of control bones three weeks after sciatic nerve section.", "contents": "Nonspecific collagenolytic activity of the femoral bone in immobilized rat extremities. Nonspecific collagenolytic activity was studied in rat bones after immobilization. The left hind limb was immobilized by sectioning the sciatic nerve. Enzyme activity was determined by using synthetic pentapeptide substrate (Pz-Pro-Leu-Gly-Pro-D-Arg). After immobilization the activity of nonspecific collagenase increased and reached its maximum on the third day after the operation. The activity was decreased after one week and attained levels of control bones three weeks after sciatic nerve section."} {"id": "PMID:167393", "title": "Kaposi's varicelliform eruption complicating local facial trauma. Case report.", "content": "A patient who had facial lacerations and then developed Kaposi's varicelliform eruption is reported. Presently, there is no specific therapy for this disease.", "contents": "Kaposi's varicelliform eruption complicating local facial trauma. Case report. A patient who had facial lacerations and then developed Kaposi's varicelliform eruption is reported. Presently, there is no specific therapy for this disease."} {"id": "PMID:167396", "title": "L-Histidine: failure to affect the sleep-waking cycle in man.", "content": "L-Histidine was administered to three patients with intractable narcolepsy (20 g/day for 2 weeks), to 4 normal volunteers (32.4 g/day for 5 days), and to a patient with progressive systemic sclerosis (48.6 g/day for 16 days). No effect was observed on noctural EEG sleep patterns in any of the subjects or on the symptoms of the patients with narcolepsy. These results fail to support the hypothesis that histamine is a waking factor.", "contents": "L-Histidine: failure to affect the sleep-waking cycle in man. L-Histidine was administered to three patients with intractable narcolepsy (20 g/day for 2 weeks), to 4 normal volunteers (32.4 g/day for 5 days), and to a patient with progressive systemic sclerosis (48.6 g/day for 16 days). No effect was observed on noctural EEG sleep patterns in any of the subjects or on the symptoms of the patients with narcolepsy. These results fail to support the hypothesis that histamine is a waking factor."} {"id": "PMID:167397", "title": "Molecur mechanism of action of the radioprotective substance WR 2721.", "content": "The radioprotective effect of WR 2721 on catalase and the type and loci of its interaction with the enzyme have been investigated by means of spectrophotometric and electron spin resonance, (ESR) methods. The radiation damage, indicated by a change in enzymatic activity and in the Soret absorption band, has been the less the larger the WR 2721 concentration. In the case of ESR investigations, addition of WR 2721 has resulted in a reduction of the spin concentration of Cu-2+. Since cysteamine has exhibited similar results, however, to a lesser extent, it can be assumed that the RS-ions are responsible for the protective effect. From the results obtained it can be concluded that (the dephosphorilized) WR 2721 forms a complex with the enzyme and acts as an electron donor.", "contents": "Molecur mechanism of action of the radioprotective substance WR 2721. The radioprotective effect of WR 2721 on catalase and the type and loci of its interaction with the enzyme have been investigated by means of spectrophotometric and electron spin resonance, (ESR) methods. The radiation damage, indicated by a change in enzymatic activity and in the Soret absorption band, has been the less the larger the WR 2721 concentration. In the case of ESR investigations, addition of WR 2721 has resulted in a reduction of the spin concentration of Cu-2+. Since cysteamine has exhibited similar results, however, to a lesser extent, it can be assumed that the RS-ions are responsible for the protective effect. From the results obtained it can be concluded that (the dephosphorilized) WR 2721 forms a complex with the enzyme and acts as an electron donor."} {"id": "PMID:167398", "title": "Roentgen features of the superficial depressed type of early gastric carcinoma.", "content": "The superficial depressed type of early gastric carcinoma is described. The macroscopic appearance is characterized by an irregular erosion, often associated with a deeper central ulceration. The surrounding mucosal folds exhibit abrupt termination, narrowing, and clubbing. The roentgen diagnosis requires good demonstrations of detail. The double-contrast technique is most important and informative and can be used to study almost any part of the stomach.", "contents": "Roentgen features of the superficial depressed type of early gastric carcinoma. The superficial depressed type of early gastric carcinoma is described. The macroscopic appearance is characterized by an irregular erosion, often associated with a deeper central ulceration. The surrounding mucosal folds exhibit abrupt termination, narrowing, and clubbing. The roentgen diagnosis requires good demonstrations of detail. The double-contrast technique is most important and informative and can be used to study almost any part of the stomach."} {"id": "PMID:167399", "title": "Intracranial tumors: correlation of angiography with dynamic radionuclide studies.", "content": "In a group of 100 supratentorial brain tumors, 23% demonstrated increased activity during the dynamic portion of the brain scan. Increased activity correlates best with the following angiographic characteristics: (a) increased size of supplying vessels, and (b) vascular supply simultaneously from both parenchymal and meningeal arteries. Increased activity has no correlation with the presence of early venous drainage, peritumoral edema, or degree of tumor vascularity and/or stain.", "contents": "Intracranial tumors: correlation of angiography with dynamic radionuclide studies. In a group of 100 supratentorial brain tumors, 23% demonstrated increased activity during the dynamic portion of the brain scan. Increased activity correlates best with the following angiographic characteristics: (a) increased size of supplying vessels, and (b) vascular supply simultaneously from both parenchymal and meningeal arteries. Increased activity has no correlation with the presence of early venous drainage, peritumoral edema, or degree of tumor vascularity and/or stain."} {"id": "PMID:167407", "title": "The effect of phlebotomy on canine erythrocyte metabolism.", "content": "Enzyme activity declines with erythrocyte age in most mammals. To test this concept in the dog, we decreased the PCV to less than 20 by phlebotomy. The erythrocytes were restored rapidly (1.57 per cent per day). The resulting decline in the mean erythrocyte age was accompanied by increased activity by most of the erythrocyte enzymes studied. Enzymes with lower initial enzymatic activity (hexokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and glutathione reductase) increased proportionally more than those with higher initial activity (lactate dehydrogenase, 3-phosphoglycerate kinase, glyceraldehyde-3-dehydrogenase and glucose-6-dehydrogenase). Among species, increases in enzyme activity after phlebotomy appear to be related to each species' life span. Most of the metabolites increased concomitantly with the highest reticulocyte period. Diphosphoglycerate concentrations did not change significantly during the experiment.", "contents": "The effect of phlebotomy on canine erythrocyte metabolism. Enzyme activity declines with erythrocyte age in most mammals. To test this concept in the dog, we decreased the PCV to less than 20 by phlebotomy. The erythrocytes were restored rapidly (1.57 per cent per day). The resulting decline in the mean erythrocyte age was accompanied by increased activity by most of the erythrocyte enzymes studied. Enzymes with lower initial enzymatic activity (hexokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and glutathione reductase) increased proportionally more than those with higher initial activity (lactate dehydrogenase, 3-phosphoglycerate kinase, glyceraldehyde-3-dehydrogenase and glucose-6-dehydrogenase). Among species, increases in enzyme activity after phlebotomy appear to be related to each species' life span. Most of the metabolites increased concomitantly with the highest reticulocyte period. Diphosphoglycerate concentrations did not change significantly during the experiment."} {"id": "PMID:167408", "title": "The demonstration by interference tests of an infective agent in fetuses from ewes inoculated with Border disease tissue.", "content": "Fetuses and placental tissues were taken from pregnant ewes at intervals varying between eight and 21 days after inoculation with tissue suspensions from cases of Border disease. Virus isolation procedures involving the detection of a cytopathic effect in tissue cultures with or without interference tests produced universally negative results but interference tests, using a plaque technique with the NADL strain of bovine virus diarrhoea virus as a challenge virus, detected the presence of an agent in tissues from six out of 10 fetuses. Inoculated ewes allowed to proceed to term showed a serological response characteristic of Border disease infection, as measured by four different tests. Although hairy shaker lambs were not seen, the occurence of abortion and stillbirth due to causes other than bacterial agents, was an indication that the Border disease agent was present. Electron microscopy of fetal fluids failed to detect viral particles.", "contents": "The demonstration by interference tests of an infective agent in fetuses from ewes inoculated with Border disease tissue. Fetuses and placental tissues were taken from pregnant ewes at intervals varying between eight and 21 days after inoculation with tissue suspensions from cases of Border disease. Virus isolation procedures involving the detection of a cytopathic effect in tissue cultures with or without interference tests produced universally negative results but interference tests, using a plaque technique with the NADL strain of bovine virus diarrhoea virus as a challenge virus, detected the presence of an agent in tissues from six out of 10 fetuses. Inoculated ewes allowed to proceed to term showed a serological response characteristic of Border disease infection, as measured by four different tests. Although hairy shaker lambs were not seen, the occurence of abortion and stillbirth due to causes other than bacterial agents, was an indication that the Border disease agent was present. Electron microscopy of fetal fluids failed to detect viral particles."} {"id": "PMID:167409", "title": "Changes in enterocyte mitochondria associated with deficiency of copper in cattle.", "content": "Comparisons were made between specimens of intestinal mucosa from three young Friesian steers, killed when showing clinical signs associated with copper deficiency, and three controls that had received supplementary copper. Copper deficiency was associated with marked depletion of cytochrome oxidase in the epithelium of the duodenum, jejunum and ileum, and with partial villus atrophy in the duodenum and jejunum. Enterocytes from the duodenum, jejunum and ileum showed mitochondrial abnormalities ranging from slight swelling to marked localised dilation. Many of the mitochondria not affected by swelling had a distinctly condensed appearance. These changes are discussed in relation to the copper-responsive diarrhoea that affects a proportion of cattle suffering from copper deficiency.", "contents": "Changes in enterocyte mitochondria associated with deficiency of copper in cattle. Comparisons were made between specimens of intestinal mucosa from three young Friesian steers, killed when showing clinical signs associated with copper deficiency, and three controls that had received supplementary copper. Copper deficiency was associated with marked depletion of cytochrome oxidase in the epithelium of the duodenum, jejunum and ileum, and with partial villus atrophy in the duodenum and jejunum. Enterocytes from the duodenum, jejunum and ileum showed mitochondrial abnormalities ranging from slight swelling to marked localised dilation. Many of the mitochondria not affected by swelling had a distinctly condensed appearance. These changes are discussed in relation to the copper-responsive diarrhoea that affects a proportion of cattle suffering from copper deficiency."} {"id": "PMID:167410", "title": "Experimental infection of calves with respiratory syncytial virus.", "content": "Three bovine isolates and one human isolate of RS virus were given intranasally to gnotobiotic, colostrum-deprived and conventional calves. All isolates produced a biphasic pyrexia associated with a serous nasal discharge. Virus was recovered from nasal secretions 4-10 days after inoculation from nasal, tracheal and bronchial mucosae and lung of animals killed 7-13 days after inoculation. Infection did not produce any macroscopic lesions, but histologically there was a focal degenerative rhinitis and a catarrhal bronchiolitis with the occasional formation of syncytia in bronchioles and alveoli.", "contents": "Experimental infection of calves with respiratory syncytial virus. Three bovine isolates and one human isolate of RS virus were given intranasally to gnotobiotic, colostrum-deprived and conventional calves. All isolates produced a biphasic pyrexia associated with a serous nasal discharge. Virus was recovered from nasal secretions 4-10 days after inoculation from nasal, tracheal and bronchial mucosae and lung of animals killed 7-13 days after inoculation. Infection did not produce any macroscopic lesions, but histologically there was a focal degenerative rhinitis and a catarrhal bronchiolitis with the occasional formation of syncytia in bronchioles and alveoli."} {"id": "PMID:167425", "title": "[Spinal chrodoma - III. Review of the literature since 1960].", "content": "Vertebral chordomas develop from the intrarachidial -- and more often the intrasomatic --vestiges of the embryonic notochord, and are rare caancers that are more likely to become manifest, usually between 30 and 40 years of age, with a painful radiculo-medullary syndrome than with the clear signs of a tumour. The insidious evolution of this type of cancer, which gives rise to few metastases, and its ambiguous radiological appearance explain why it is usually diagnosed late after an anatomo-pathological examination. The fundamental histological element is the physaliphorous cell, ultrastructural studies of which have demonstrated that the large \"mucous\" inclusions of interstitial material. The discovery, by Murad and Murthy, of particles enclosed in a membrane in the chordomatous cells indicates possible viral involvement. Radio-surgical treatment results in more comfortable survival (very variable) although it involves repeated high-dose cobalto-therapy and repeated surgical excisions.", "contents": "[Spinal chrodoma - III. Review of the literature since 1960]. Vertebral chordomas develop from the intrarachidial -- and more often the intrasomatic --vestiges of the embryonic notochord, and are rare caancers that are more likely to become manifest, usually between 30 and 40 years of age, with a painful radiculo-medullary syndrome than with the clear signs of a tumour. The insidious evolution of this type of cancer, which gives rise to few metastases, and its ambiguous radiological appearance explain why it is usually diagnosed late after an anatomo-pathological examination. The fundamental histological element is the physaliphorous cell, ultrastructural studies of which have demonstrated that the large \"mucous\" inclusions of interstitial material. The discovery, by Murad and Murthy, of particles enclosed in a membrane in the chordomatous cells indicates possible viral involvement. Radio-surgical treatment results in more comfortable survival (very variable) although it involves repeated high-dose cobalto-therapy and repeated surgical excisions."} {"id": "PMID:167426", "title": "[Determination of urinary cyclic AMP in phosphorus and calcium pathology].", "content": "Quantitative analysis of urinary cyclic AMP in phospho-calcic pathology. The authors describe a method measuring amounts of cyclic AMP. Normal daily elimination in urine was measured in a group of normal subjects. Elimination was found to be raised in two-thirds of the patients with primary hyperparathryroidism, normal in those with idiopathic hypercalcaemia and neoplastic hypercalcaemia, and subnormal in patients with hypoparathyroidism. The urinary excretion of cyclic AMP after perfusion of parathyroid hormone was very low in cases of pseudo-hypoparathyroidism compared with that in surgical hypoparathroid controls. The results are compared with data from the literature. The theoretical and diagnostic value of these quantitative analyses is discussed.", "contents": "[Determination of urinary cyclic AMP in phosphorus and calcium pathology]. Quantitative analysis of urinary cyclic AMP in phospho-calcic pathology. The authors describe a method measuring amounts of cyclic AMP. Normal daily elimination in urine was measured in a group of normal subjects. Elimination was found to be raised in two-thirds of the patients with primary hyperparathryroidism, normal in those with idiopathic hypercalcaemia and neoplastic hypercalcaemia, and subnormal in patients with hypoparathyroidism. The urinary excretion of cyclic AMP after perfusion of parathyroid hormone was very low in cases of pseudo-hypoparathyroidism compared with that in surgical hypoparathroid controls. The results are compared with data from the literature. The theoretical and diagnostic value of these quantitative analyses is discussed."} {"id": "PMID:167428", "title": "Turnover of plasma total and very low density lipoprotein triglyceride in man.", "content": "Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg - kg-1- hr-1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg - kg-1 - hr-1. A highly significant correlation was present between the two turnover rates (r equal + 0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics.", "contents": "Turnover of plasma total and very low density lipoprotein triglyceride in man. Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg - kg-1- hr-1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg - kg-1 - hr-1. A highly significant correlation was present between the two turnover rates (r equal + 0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics."} {"id": "PMID:167429", "title": "The esterification of cholesterol in plasma after acute myocardial infarction.", "content": "The rate of plasma cholesterol esterification (LCAT activity) and the concentration of eight proteins in the plasma have been studied in the ten male patients during the course of acute myocardial infarction. Samples were drawn 22 hr, 3 days, 8 days, 2 weeks, and 7 weeks after the onset of the acute myocardial infarction. The changes of the plasma proteins were typical for the acute-phase reaction. LCAT activity decreased initially during the illness. The lowest values were found after 8 days. Concomitantly, a reducation in the plasma concentration of total and free cholesterol and cholesteryl esters was demonstrated. The rate of cholesterol esterification correlated significantly with the concentration of prealbumin, alpha-lipoprotein, and albumin. Seven weeks after onset of the infarction, the LCAT values were equal to those in a reference group. The results suggest that the synthesis of LCAT was decreased during the acute-phase reaction.", "contents": "The esterification of cholesterol in plasma after acute myocardial infarction. The rate of plasma cholesterol esterification (LCAT activity) and the concentration of eight proteins in the plasma have been studied in the ten male patients during the course of acute myocardial infarction. Samples were drawn 22 hr, 3 days, 8 days, 2 weeks, and 7 weeks after the onset of the acute myocardial infarction. The changes of the plasma proteins were typical for the acute-phase reaction. LCAT activity decreased initially during the illness. The lowest values were found after 8 days. Concomitantly, a reducation in the plasma concentration of total and free cholesterol and cholesteryl esters was demonstrated. The rate of cholesterol esterification correlated significantly with the concentration of prealbumin, alpha-lipoprotein, and albumin. Seven weeks after onset of the infarction, the LCAT values were equal to those in a reference group. The results suggest that the synthesis of LCAT was decreased during the acute-phase reaction."} {"id": "PMID:167430", "title": "Herpesvirus hominis infections in renal transplant recipients.", "content": "A longitudinal, prospective study of herpesvirus hominis (HVH, herpes simplex virus) was carried out in immunosuppressed renal allograft recipients using serologic, virologic and clinical techniques. The final study group consisted of 37 patients of which 31 were followed for at least 2 months and 26 for more than 1 year. A 4-fold rise or more in HVH complement-fixing antibody in relation to titers measured at the time of transplantation was found in 11 patients. Eight of these 11 patients had clinically recognizable herpetic lesions. An additional 9 patients had lesions without titer rise being demonstrable. The 20 of the 37 patients studied (54%) had evidence of active infection with HVH. Because of pain and discomfort herpetic sores were of clinical importance in 11 patients and lasted for 1 month or more in 9. Herpetic keratitis was seen in 3 and left permanent damage to sight in 2. Multiple, extensive, prolonged and sometimes destructive herpetic lesions affected 5 (16%) of all patients studied.", "contents": "Herpesvirus hominis infections in renal transplant recipients. A longitudinal, prospective study of herpesvirus hominis (HVH, herpes simplex virus) was carried out in immunosuppressed renal allograft recipients using serologic, virologic and clinical techniques. The final study group consisted of 37 patients of which 31 were followed for at least 2 months and 26 for more than 1 year. A 4-fold rise or more in HVH complement-fixing antibody in relation to titers measured at the time of transplantation was found in 11 patients. Eight of these 11 patients had clinically recognizable herpetic lesions. An additional 9 patients had lesions without titer rise being demonstrable. The 20 of the 37 patients studied (54%) had evidence of active infection with HVH. Because of pain and discomfort herpetic sores were of clinical importance in 11 patients and lasted for 1 month or more in 9. Herpetic keratitis was seen in 3 and left permanent damage to sight in 2. Multiple, extensive, prolonged and sometimes destructive herpetic lesions affected 5 (16%) of all patients studied."} {"id": "PMID:167431", "title": "Antibiotic susceptibility testing of anaerobic bacteria by the standardized disc diffusion method with special reference to bacteroides fragilis.", "content": "The susceptibility of 90 strains of Bacteroides fragilis to 16 antibacterial drugs was determined by the agar plate dilution test and the disc diffusion test. Good correlation of results was obtained with the two methods, and regression line analysis could be performed for beta-lactam antibiotics, erythromycin, tetracyclines, lincomycin and clindamycin. Thus the standardized disc diffusion method can be used for susceptibility testing, but only a clear distinction between sensitive and resistant strains can be seen.", "contents": "Antibiotic susceptibility testing of anaerobic bacteria by the standardized disc diffusion method with special reference to bacteroides fragilis. The susceptibility of 90 strains of Bacteroides fragilis to 16 antibacterial drugs was determined by the agar plate dilution test and the disc diffusion test. Good correlation of results was obtained with the two methods, and regression line analysis could be performed for beta-lactam antibiotics, erythromycin, tetracyclines, lincomycin and clindamycin. Thus the standardized disc diffusion method can be used for susceptibility testing, but only a clear distinction between sensitive and resistant strains can be seen."} {"id": "PMID:167432", "title": "[Complications in primary tumors of the small intestine].", "content": "Of 112 000 patients undergoing surgery between 1952 and 1973, 67 had a primary tumor of the small intestine. 22 patients had a benign tumor, 8 a carcinoid, 21 carcinoma and 15 sarcoma. Benign tumors were more frequent in the duodenum and ileum, carcinoids in the terminal ileum and carcinomas in the duodenum and jejunum. Sarcomas were found equally in all parts of the small intestine. The most common symptom for all types of the tumor was variable pain in the abdomen. Loss of weight occurred only in patients with carcinomas and sarcomas; heavy intestinal blood loss was most common in patients with benign tumors. Benign tumors often show invagination, while sarcomas cause occlusive ileus or perforation. All duodenal tumors show heavy intestinal bleeding but hematemesis is rare. Emergency surgery was necessary in 42% of patients with benign tumors or sarcoma and in 30% of patients with carcinoma. Five-year survival in patients with benign tumors is excellent (100%). Compared to this, five-year survival in patients with carcinoma, sarcoma or carcinoids is only 15%.", "contents": "[Complications in primary tumors of the small intestine]. Of 112 000 patients undergoing surgery between 1952 and 1973, 67 had a primary tumor of the small intestine. 22 patients had a benign tumor, 8 a carcinoid, 21 carcinoma and 15 sarcoma. Benign tumors were more frequent in the duodenum and ileum, carcinoids in the terminal ileum and carcinomas in the duodenum and jejunum. Sarcomas were found equally in all parts of the small intestine. The most common symptom for all types of the tumor was variable pain in the abdomen. Loss of weight occurred only in patients with carcinomas and sarcomas; heavy intestinal blood loss was most common in patients with benign tumors. Benign tumors often show invagination, while sarcomas cause occlusive ileus or perforation. All duodenal tumors show heavy intestinal bleeding but hematemesis is rare. Emergency surgery was necessary in 42% of patients with benign tumors or sarcoma and in 30% of patients with carcinoma. Five-year survival in patients with benign tumors is excellent (100%). Compared to this, five-year survival in patients with carcinoma, sarcoma or carcinoids is only 15%."} {"id": "PMID:167434", "title": "Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate.", "content": "The in vitro destruction of tumor cells by specifically sensitized mouse lymphocytes was inhibited by adenosine; this inhibition was markedly potentiated by the presence of an inhibitor of adenosine deaminase. The inhibition of cytolysis by adenosine was accompanied by a rapid elevation in lymphocytic adenosine 3',5'-monophosphate (cyclic AMP) concentrations. Both the inhibition of cytolysis and the elevation of cyclic AMP were reversed by prolonged incubation of the lymphocytes in the presence of adenosine or, more rapidly, by removal of the adenosine. Low concentrations of adenosine also caused an elevation of cyclic AMP in human lymphocytes, and this effect of adenosine may contribute to the lack of immune response associated with adenosine deaminase deficiency.", "contents": "Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. The in vitro destruction of tumor cells by specifically sensitized mouse lymphocytes was inhibited by adenosine; this inhibition was markedly potentiated by the presence of an inhibitor of adenosine deaminase. The inhibition of cytolysis by adenosine was accompanied by a rapid elevation in lymphocytic adenosine 3',5'-monophosphate (cyclic AMP) concentrations. Both the inhibition of cytolysis and the elevation of cyclic AMP were reversed by prolonged incubation of the lymphocytes in the presence of adenosine or, more rapidly, by removal of the adenosine. Low concentrations of adenosine also caused an elevation of cyclic AMP in human lymphocytes, and this effect of adenosine may contribute to the lack of immune response associated with adenosine deaminase deficiency."} {"id": "PMID:167435", "title": "Cell-mediated immunity to antigens associated with endogenous murine C-type leukemia viruses.", "content": "Splenic lymphocytes from (BALB/c times A/J) F 1 mice are cytotoxic for BALB/c fibroblasts infected with an endogenous C-type leukemia virus, but are not cytotoxic for uninfected BALB/c fibroblasts. These results indicate that mice do not exhibit cell-mediated immune tolerance to antigens associated with endogenous C-type viruses.", "contents": "Cell-mediated immunity to antigens associated with endogenous murine C-type leukemia viruses. Splenic lymphocytes from (BALB/c times A/J) F 1 mice are cytotoxic for BALB/c fibroblasts infected with an endogenous C-type leukemia virus, but are not cytotoxic for uninfected BALB/c fibroblasts. These results indicate that mice do not exhibit cell-mediated immune tolerance to antigens associated with endogenous C-type viruses."} {"id": "PMID:167436", "title": "Changes in protein levels in perfusates of freely moving cats: relation to behavioral state.", "content": "Perfusates from the brains of freely moving cats, obtained by means of a push-pull cannula, contain high concentrations of proteins. The levels vary in a cyclic fashion and are higher during rapid eye movement sleep than during the waking state. The proteins represent a distinctive class of tissue protein and their changing levels appear to reflect an alteration in the protein content of the extracellular space of brain related to behavioral state.", "contents": "Changes in protein levels in perfusates of freely moving cats: relation to behavioral state. Perfusates from the brains of freely moving cats, obtained by means of a push-pull cannula, contain high concentrations of proteins. The levels vary in a cyclic fashion and are higher during rapid eye movement sleep than during the waking state. The proteins represent a distinctive class of tissue protein and their changing levels appear to reflect an alteration in the protein content of the extracellular space of brain related to behavioral state."} {"id": "PMID:167437", "title": "Immunofluorescent localization of cyclic AMP in toad urinary bladder: possible intercellular transfer.", "content": "By use of an immunofluorescent cytochemical staining technique, adenosine 3',5'-monophosphate (cyclic AMP) has been localized in toad bladder epithelial cells. Within 2 minutes after addition of vasopressin, staining intensity increases in both mitochondria-rich and granular cells. This finding, taken together with the precise anatomical relation between these two epithelial cell types and the observation that after separation of the two cell types vasopressin stimulates cyclic AMP accumulation in only mitochondria-rich cells, suggests that cyclic AMP may be transferred from mitochrondria-rich to granular cells as part of the response of the toad urinary bladder to vasopressin.", "contents": "Immunofluorescent localization of cyclic AMP in toad urinary bladder: possible intercellular transfer. By use of an immunofluorescent cytochemical staining technique, adenosine 3',5'-monophosphate (cyclic AMP) has been localized in toad bladder epithelial cells. Within 2 minutes after addition of vasopressin, staining intensity increases in both mitochondria-rich and granular cells. This finding, taken together with the precise anatomical relation between these two epithelial cell types and the observation that after separation of the two cell types vasopressin stimulates cyclic AMP accumulation in only mitochondria-rich cells, suggests that cyclic AMP may be transferred from mitochrondria-rich to granular cells as part of the response of the toad urinary bladder to vasopressin."} {"id": "PMID:167439", "title": "Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation.", "content": "Cyclic adenosine monophosphate (cyclic AMP) and 11 derivatives were applied to rat cerebellar Purkinje cells by iontophoresis. Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively. The ability of the 11 analogs to inhibit neuronal firing correlated ( r= + .78) with their reported potency in activating cyclic AMP-dependent protein kinase. These results extend previous studies, pointing to the mediation by cyclic AMP of the noradrenergic inhibition of Purkinje neurons, and provide new physiological evidence that protein phosphorylation is a major step in the action of cyclic AMP.", "contents": "Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation. Cyclic adenosine monophosphate (cyclic AMP) and 11 derivatives were applied to rat cerebellar Purkinje cells by iontophoresis. Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively. The ability of the 11 analogs to inhibit neuronal firing correlated ( r= + .78) with their reported potency in activating cyclic AMP-dependent protein kinase. These results extend previous studies, pointing to the mediation by cyclic AMP of the noradrenergic inhibition of Purkinje neurons, and provide new physiological evidence that protein phosphorylation is a major step in the action of cyclic AMP."} {"id": "PMID:167440", "title": "[Transcobalamins in megaloblastic anemias].", "content": "Transcobalamins are proteins which carry vitamin B12 and which are normally partly unsaturated. This study of transcobalamins was carried out in 17 subjects with megaloblastic anemia (12 true cases of pernicious anemia and 5 cases of folate deficiency). Among the latter, the transcobalamins were studied in 4 cases of pernicious anemia, before and after treatment with vitamin B12. The distribution of endogenous B12 was determined in four normal controls and two cases of pernicious anemia. This vitamin is normally distributed roughly equally between the three transcobalamins, whereas in B12 deficiency, T.C.2 is very unsaturated together with T.C.1 to a lesser degree. The latent fixation capacity of the serum is increased together with the latent fixation capacity of T.C. I and, above all, T.C. II but that of T.C. III is reduced in patients with pernicious anemia. In folate deficiency, only the latent fixation capacity of T.C. II is increased. When vitamin B12 is administered in physiological dosage, T.C. I becomes gradually saturated. In pharmacological dosage, total fixation capacity together with that of T.C. I and T.C. II become gradually reduced, but in spite of high levels of circulating B12, these proteins remain partially unsaturated. Various theories are suggested to explain the variations of these three transcobalamins in megaloblastic anemia but the problem is still unclear.", "contents": "[Transcobalamins in megaloblastic anemias]. Transcobalamins are proteins which carry vitamin B12 and which are normally partly unsaturated. This study of transcobalamins was carried out in 17 subjects with megaloblastic anemia (12 true cases of pernicious anemia and 5 cases of folate deficiency). Among the latter, the transcobalamins were studied in 4 cases of pernicious anemia, before and after treatment with vitamin B12. The distribution of endogenous B12 was determined in four normal controls and two cases of pernicious anemia. This vitamin is normally distributed roughly equally between the three transcobalamins, whereas in B12 deficiency, T.C.2 is very unsaturated together with T.C.1 to a lesser degree. The latent fixation capacity of the serum is increased together with the latent fixation capacity of T.C. I and, above all, T.C. II but that of T.C. III is reduced in patients with pernicious anemia. In folate deficiency, only the latent fixation capacity of T.C. II is increased. When vitamin B12 is administered in physiological dosage, T.C. I becomes gradually saturated. In pharmacological dosage, total fixation capacity together with that of T.C. I and T.C. II become gradually reduced, but in spite of high levels of circulating B12, these proteins remain partially unsaturated. Various theories are suggested to explain the variations of these three transcobalamins in megaloblastic anemia but the problem is still unclear."} {"id": "PMID:167441", "title": "[Search for anti-intrinsic factor antibodies in the diagnosis of Biermer's anemia].", "content": "The diagnostic interest of a search for anti-intrinsic factor antibodies is emphasized from the authors research on more than 200 patients or controls. Antibodies of type I, so-called blocking antibodies, were detected in 66% of cases where the diagnosis of pernicious anemia was made. Type II, so-called precipitating antibodies, were found in 47% of patients with antibodies of type I and only in the latter. Certain etiological factors, already noted in the world literature, were found, in particular the link with the female sex and with blood group A. The specificity of these antibodies is very great and false positives are exceptional. We did not find them in any of the 104 controls. They were observed, however, in 5 of the 56 patients where the diagnosis of pernicious anemia was not definite, but it is likely that, in these 5 cases, pernicious anemia existed with some other disease. Our study also showed the limits of other methods of investigation of this disease; hypovitaminimia B12 is often corrected by treatment without proper inductions and B12 malabsorption on the Schilling test may not be corrected by the addition of intrinsic factor.", "contents": "[Search for anti-intrinsic factor antibodies in the diagnosis of Biermer's anemia]. The diagnostic interest of a search for anti-intrinsic factor antibodies is emphasized from the authors research on more than 200 patients or controls. Antibodies of type I, so-called blocking antibodies, were detected in 66% of cases where the diagnosis of pernicious anemia was made. Type II, so-called precipitating antibodies, were found in 47% of patients with antibodies of type I and only in the latter. Certain etiological factors, already noted in the world literature, were found, in particular the link with the female sex and with blood group A. The specificity of these antibodies is very great and false positives are exceptional. We did not find them in any of the 104 controls. They were observed, however, in 5 of the 56 patients where the diagnosis of pernicious anemia was not definite, but it is likely that, in these 5 cases, pernicious anemia existed with some other disease. Our study also showed the limits of other methods of investigation of this disease; hypovitaminimia B12 is often corrected by treatment without proper inductions and B12 malabsorption on the Schilling test may not be corrected by the addition of intrinsic factor."} {"id": "PMID:167442", "title": "[Biermer's anemia with chronic lymphoid leukemia and hemolysis with autoantibodies].", "content": "The authors report a case of chronic lymphatic leukemia occurring four years after the onset of pernicious anemia. Multiple immunological abnormalities were detected. Hemolytic anemia with auto-antibodies and anti-thyroglobulin antibodies. Anti-intrinsic factor antibodies of type 1 were found but disappeared later. This case, the 9 th in the world literature, emphasizes the links between pernicious anemia, an auto-immune disease, and malignant disorders of the lymphatic and immune systems.", "contents": "[Biermer's anemia with chronic lymphoid leukemia and hemolysis with autoantibodies]. The authors report a case of chronic lymphatic leukemia occurring four years after the onset of pernicious anemia. Multiple immunological abnormalities were detected. Hemolytic anemia with auto-antibodies and anti-thyroglobulin antibodies. Anti-intrinsic factor antibodies of type 1 were found but disappeared later. This case, the 9 th in the world literature, emphasizes the links between pernicious anemia, an auto-immune disease, and malignant disorders of the lymphatic and immune systems."} {"id": "PMID:167443", "title": "[Folate deficiency and neurologic disorders].", "content": "Estimation of serum folate was carried out in 74 patients with various neurological disorders. Levels less than normal were detected in 63 of them, with mainly peripheral neuritis, cerebellar syndromes and/or psychological disorders. The role of certain etiological factors was demonstrated, e.g. alcoholism, malnutrition, diarrhea, anti-epileptic treatment. Links between these neurological disorders and the folate deficiency remain to be demonstrated. In at least 8 cases, treatment with folic acid seems to have had a favourable influence on the course of these disorders.", "contents": "[Folate deficiency and neurologic disorders]. Estimation of serum folate was carried out in 74 patients with various neurological disorders. Levels less than normal were detected in 63 of them, with mainly peripheral neuritis, cerebellar syndromes and/or psychological disorders. The role of certain etiological factors was demonstrated, e.g. alcoholism, malnutrition, diarrhea, anti-epileptic treatment. Links between these neurological disorders and the folate deficiency remain to be demonstrated. In at least 8 cases, treatment with folic acid seems to have had a favourable influence on the course of these disorders."} {"id": "PMID:167444", "title": "[Macrocytic animia due to the combination trimethoprim-sulfamethoxazole].", "content": "The authors report a case of macrocytic anemia due to folate deficiency occurring suddenly after the administration of trimethoprime-sulfamethoxazole and completely cured by folic acid. This type of complication occurs particularly often in patients who already have a relative folate deficiency. In our case only moderate alcoholism was found. Thus individual predisposition due to enzyme abnormality must be considered. Prophylactic administration of folic acid in patients receiving this drug association is thus advisable.", "contents": "[Macrocytic animia due to the combination trimethoprim-sulfamethoxazole]. The authors report a case of macrocytic anemia due to folate deficiency occurring suddenly after the administration of trimethoprime-sulfamethoxazole and completely cured by folic acid. This type of complication occurs particularly often in patients who already have a relative folate deficiency. In our case only moderate alcoholism was found. Thus individual predisposition due to enzyme abnormality must be considered. Prophylactic administration of folic acid in patients receiving this drug association is thus advisable."} {"id": "PMID:167445", "title": "[Lysozyme in hematologic diseases].", "content": "Blood lysozyme estimation seems to be important in hematological practice. Serum levels are roughly proportional to the size of the pool and, above all, granulocytic renewal. Thus levels are increased compared with levels of circulating polynuclear cells. In bone marrow disorders, and particularly in myelofibrosis, owing to the infective granulopoiesis and/or increased destruction of the neutrophil polymorphs. It is lowered in neutropenia with a scanty bone marrow. It provides an important contribution to diagnosis of the type of acute leukemia, the fall in the lymphoblastic forms contrast with normal or increased levels in myeloblastic forms. Finally, there is a marked increase in lysosome urea in acute monocytic or myelomonocytic leukemia.", "contents": "[Lysozyme in hematologic diseases]. Blood lysozyme estimation seems to be important in hematological practice. Serum levels are roughly proportional to the size of the pool and, above all, granulocytic renewal. Thus levels are increased compared with levels of circulating polynuclear cells. In bone marrow disorders, and particularly in myelofibrosis, owing to the infective granulopoiesis and/or increased destruction of the neutrophil polymorphs. It is lowered in neutropenia with a scanty bone marrow. It provides an important contribution to diagnosis of the type of acute leukemia, the fall in the lymphoblastic forms contrast with normal or increased levels in myeloblastic forms. Finally, there is a marked increase in lysosome urea in acute monocytic or myelomonocytic leukemia."} {"id": "PMID:167453", "title": "Surveillance of enterovirus infections in Bangkok. I. Isolation of enterovirus from faecal specimens of healthy children.", "content": "During the period August 1970 through July 1973, about 50 faecal specimens collected each month from healthy pre-school children of lower economic status in Bangkok were studied for virus isolation using primary monkey kidney cells and new born mice. From a total of 1,823 samples, 557 (30.5%) were positive: 86 (4.8%) polioviruses, 77 (4.2%) coxsackieviruses B, 223 (12.2%) echoviruses, and 127 strains (7.0%) of unidentified viruses. Altogether, 45 serotypes of enteric viruses were identified. More than 30 serotypes, including the 3 types of poliovirus, were present each year. Infection rates were higher in males than in females and highest at one year of age, the rates decreasing with progressing age. There was no marked seasonal variation of enterovirus infections in Bangkok. The poliovirus infection index was low from September to January, and the index of polio and non-polio enterovirus infections was highest in April.", "contents": "Surveillance of enterovirus infections in Bangkok. I. Isolation of enterovirus from faecal specimens of healthy children. During the period August 1970 through July 1973, about 50 faecal specimens collected each month from healthy pre-school children of lower economic status in Bangkok were studied for virus isolation using primary monkey kidney cells and new born mice. From a total of 1,823 samples, 557 (30.5%) were positive: 86 (4.8%) polioviruses, 77 (4.2%) coxsackieviruses B, 223 (12.2%) echoviruses, and 127 strains (7.0%) of unidentified viruses. Altogether, 45 serotypes of enteric viruses were identified. More than 30 serotypes, including the 3 types of poliovirus, were present each year. Infection rates were higher in males than in females and highest at one year of age, the rates decreasing with progressing age. There was no marked seasonal variation of enterovirus infections in Bangkok. The poliovirus infection index was low from September to January, and the index of polio and non-polio enterovirus infections was highest in April."} {"id": "PMID:167454", "title": "Parasitology survey and seroepidemiology of amoebiasis in South Kalimantan (Borneo), Indonesia.", "content": "A parasitology surevy was conducted among inhabitants of 7 villages in 3 regencies in South Kalimantan Province, Indonesia. A total of 2,169 stool specimens, 2,756 blood smears and 1,027 serum specimens were obtained, representing samples from approximately 10%, 12% and 5% of the population, respectively. One to 8 different intestinal parasitic infections were detected in 97% of the people. Those parasites most frequently found were Trichuris trichiura (83%), Ascaris lumbricoides (79%), and hookworm (65%), followed by Entamoeba coli (37%), Endolimaxnana (12%), Entamoeba histolytica (12%), Iodamoeba b\u00fctschlii (11%), Giardia lamblia (5%), Entamoeba hartmanni (2%), Chilomastix mesnili (2%). Other parasites found were Enterobius vermicularis, Strongyloides stercoralis, Capillaria sp., Echinostoma sp., Hymenolepis diminuta, and Trichomonas hominis. Giardia lamblia was found more often in younger people and Entamoeba coli, Iodamoeba b\u00fctschlii and hookworm in the older age group. Ascaris lumbricoides occurred more frequently in females, and hookworm in males. Plasmodium vivax and Plasmodium falciparum were found in the blood smears of 4.4% of the people, mostly in the younger age groups. Seroepidemiological studies on amoebiasis were done by use of the indirect hemagglutination test with antigens prepared from the HK9 strain of Entamoeba histolytica maintained in axenic cultures. The frequency distribution of the reciprocal antibody titers showed a bimodal distribution with 34% of the population demonstrating positive reactions at titers of 1:128 or greater.", "contents": "Parasitology survey and seroepidemiology of amoebiasis in South Kalimantan (Borneo), Indonesia. A parasitology surevy was conducted among inhabitants of 7 villages in 3 regencies in South Kalimantan Province, Indonesia. A total of 2,169 stool specimens, 2,756 blood smears and 1,027 serum specimens were obtained, representing samples from approximately 10%, 12% and 5% of the population, respectively. One to 8 different intestinal parasitic infections were detected in 97% of the people. Those parasites most frequently found were Trichuris trichiura (83%), Ascaris lumbricoides (79%), and hookworm (65%), followed by Entamoeba coli (37%), Endolimaxnana (12%), Entamoeba histolytica (12%), Iodamoeba b\u00fctschlii (11%), Giardia lamblia (5%), Entamoeba hartmanni (2%), Chilomastix mesnili (2%). Other parasites found were Enterobius vermicularis, Strongyloides stercoralis, Capillaria sp., Echinostoma sp., Hymenolepis diminuta, and Trichomonas hominis. Giardia lamblia was found more often in younger people and Entamoeba coli, Iodamoeba b\u00fctschlii and hookworm in the older age group. Ascaris lumbricoides occurred more frequently in females, and hookworm in males. Plasmodium vivax and Plasmodium falciparum were found in the blood smears of 4.4% of the people, mostly in the younger age groups. Seroepidemiological studies on amoebiasis were done by use of the indirect hemagglutination test with antigens prepared from the HK9 strain of Entamoeba histolytica maintained in axenic cultures. The frequency distribution of the reciprocal antibody titers showed a bimodal distribution with 34% of the population demonstrating positive reactions at titers of 1:128 or greater."} {"id": "PMID:167457", "title": "Unusual malignant tumours of the maxilary sinuses.", "content": "Six rare tumours of the maxillary sinus occuring in South African Blacks are described. The incidence of sarcomas and tumours of glandular epithelium in the nasal sinus region is discussed and the literature is reviewed.", "contents": "Unusual malignant tumours of the maxilary sinuses. Six rare tumours of the maxillary sinus occuring in South African Blacks are described. The incidence of sarcomas and tumours of glandular epithelium in the nasal sinus region is discussed and the literature is reviewed."} {"id": "PMID:167458", "title": "Plasma fatty acids and the control of lipolysis by cathecholamines.", "content": "The role of lipolysis in adipose tissue is described in relation to the maintentance of plasma levels of fatty acids. The molecular details of the hormonal control of lipolysis in the human adipocyte are discussed.", "contents": "Plasma fatty acids and the control of lipolysis by cathecholamines. The role of lipolysis in adipose tissue is described in relation to the maintentance of plasma levels of fatty acids. The molecular details of the hormonal control of lipolysis in the human adipocyte are discussed."} {"id": "PMID:167459", "title": "Errors in metabolic regulation. A regulatory defect in the human adipocyte.", "content": "Some of the control elements required for the fine regulation of metabolic processes in the adipocyte are described. These include substrate carriers, hormone receptors, allosteric enzymes and template surfaces. A possible example of an acquired defect of a rate-determining enzyme of glycolysis in the lipoma adipocyte is described. This is manifest as an impaired sensitivity of phosphofructokinase to feedback inhibtion by citrate. The orgin and consequences of this lesion are discussed.", "contents": "Errors in metabolic regulation. A regulatory defect in the human adipocyte. Some of the control elements required for the fine regulation of metabolic processes in the adipocyte are described. These include substrate carriers, hormone receptors, allosteric enzymes and template surfaces. A possible example of an acquired defect of a rate-determining enzyme of glycolysis in the lipoma adipocyte is described. This is manifest as an impaired sensitivity of phosphofructokinase to feedback inhibtion by citrate. The orgin and consequences of this lesion are discussed."} {"id": "PMID:167460", "title": "Epipodophyllotoxin (VP 16-213) in the treatmetn of diffuse histiocytic lymphoma.", "content": "Twenty-seven patients with diffuse histiocytic lymphoma, of whom 20 had failed to respond to all other forms of chemotherapy and radiotherapy, were treated with intravenous VP 16-213. Initial dramatic response was obtained in 5 (19%), good objective response in 12 (4%), and the remaining 10 (37%) either failed to respond or thad only minimal objective change in theri disease status. The response characteristically occured within two courses of therapy, but 8 of the 17 (47relapsed at this stage resulted in remission again begin achieved in these patients. It is concluded that VP 16-213 is an effective agent in diffuse histiocytic lymphoma, but it is of limited value when used as a single agent. This drug has surprisingly little myelotoxicity, and prospective studies are now in progress to evaluate its role in combination therapy.", "contents": "Epipodophyllotoxin (VP 16-213) in the treatmetn of diffuse histiocytic lymphoma. Twenty-seven patients with diffuse histiocytic lymphoma, of whom 20 had failed to respond to all other forms of chemotherapy and radiotherapy, were treated with intravenous VP 16-213. Initial dramatic response was obtained in 5 (19%), good objective response in 12 (4%), and the remaining 10 (37%) either failed to respond or thad only minimal objective change in theri disease status. The response characteristically occured within two courses of therapy, but 8 of the 17 (47relapsed at this stage resulted in remission again begin achieved in these patients. It is concluded that VP 16-213 is an effective agent in diffuse histiocytic lymphoma, but it is of limited value when used as a single agent. This drug has surprisingly little myelotoxicity, and prospective studies are now in progress to evaluate its role in combination therapy."} {"id": "PMID:167461", "title": "[Clinical characteristics and genetic identity of the basal cell nevus syndrome (Gorlin-Goltz syndrome)].", "content": "The clinical, genetic, radiological, dental and dermatological aspects of 3 patients with the autosomal dominant basal cell naevus syndrome are reported. An analysis of the phenotypic features of 72 cases described in the literature is presented and compared with a previous analysis. Ash leaf hypopigmentation similar to that found in tuberous sclerosis represents a unique finding in this syndrome. Other similarities to the phacomatoses are discussed. We were able to support a previous report that patients with the basal cell naevus syndrome have a normal end-organ response to parathormone stimulation, and that it is most probably not related to pseudohypoparathyroidism, as earlier reports suggested.", "contents": "[Clinical characteristics and genetic identity of the basal cell nevus syndrome (Gorlin-Goltz syndrome)]. The clinical, genetic, radiological, dental and dermatological aspects of 3 patients with the autosomal dominant basal cell naevus syndrome are reported. An analysis of the phenotypic features of 72 cases described in the literature is presented and compared with a previous analysis. Ash leaf hypopigmentation similar to that found in tuberous sclerosis represents a unique finding in this syndrome. Other similarities to the phacomatoses are discussed. We were able to support a previous report that patients with the basal cell naevus syndrome have a normal end-organ response to parathormone stimulation, and that it is most probably not related to pseudohypoparathyroidism, as earlier reports suggested."} {"id": "PMID:167462", "title": "Current management of hepatic tumors.", "content": "Today, the presence of a hepatic tumor can be diagnosed with considerable accuracy by means of isotope scans, arteriogram and ultrasonic imaging. Its localization to one lobe or other lobes is also generally achievable but with less accuracy because it is not yet possible to visualize the interlobar fissure by a noninvasive technique. Exploratory laparotomy with a view to resection is the preferred approach if the patient is in good general condition. Percutaneous biopsy of a hepatic lesion should be avoided unless laparotomy is not contemplated. Resection is the mainstay of therapy for all forms of hepatic malignant tumors and is the only modality that gives some prospect of cure. The prohibitively high operative mortality rate of former years, mostly due to hemorrhage, has gradually decreased with improved understanding of hepatic anatomy and innovations in surgical technique. By means of adequate vascular control and, if necessary, parenchymal cold perfusion, major resections of difficult and bulky lesions can now be accomplished with safety. Systemic chemotherapy with single agents, intra-arterial infusion chemotherapy and hepatic dearterialization have each been found to be of modest therapeutic value in a variable proportion of patients with diffuse unresectable cancer of the liver. The results of current experience indicate that the response rate is not high and long term control of tumor is rare. Multiple drug combinations with or without infusion therapy or dearterialization are being tried in many centers. Therapeutic strategy and end results for the different forms of benign and malignant neoplasms of the liver are discussed.", "contents": "Current management of hepatic tumors. Today, the presence of a hepatic tumor can be diagnosed with considerable accuracy by means of isotope scans, arteriogram and ultrasonic imaging. Its localization to one lobe or other lobes is also generally achievable but with less accuracy because it is not yet possible to visualize the interlobar fissure by a noninvasive technique. Exploratory laparotomy with a view to resection is the preferred approach if the patient is in good general condition. Percutaneous biopsy of a hepatic lesion should be avoided unless laparotomy is not contemplated. Resection is the mainstay of therapy for all forms of hepatic malignant tumors and is the only modality that gives some prospect of cure. The prohibitively high operative mortality rate of former years, mostly due to hemorrhage, has gradually decreased with improved understanding of hepatic anatomy and innovations in surgical technique. By means of adequate vascular control and, if necessary, parenchymal cold perfusion, major resections of difficult and bulky lesions can now be accomplished with safety. Systemic chemotherapy with single agents, intra-arterial infusion chemotherapy and hepatic dearterialization have each been found to be of modest therapeutic value in a variable proportion of patients with diffuse unresectable cancer of the liver. The results of current experience indicate that the response rate is not high and long term control of tumor is rare. Multiple drug combinations with or without infusion therapy or dearterialization are being tried in many centers. Therapeutic strategy and end results for the different forms of benign and malignant neoplasms of the liver are discussed."} {"id": "PMID:167463", "title": "Gliobastoma multiforme of the cerebellum.", "content": "Glioblastoma multiforme of the cerebellum is rare. Approximately 33 case of cerebellar glioblastoma have been reported. Two-thirds of the cases occurred in adults and the male to female ratio was 2:1. The mean age was 46.7 years in adults and 10.4 years in children. Most of the tumors were lateral in location. Two of the patients (6%) had multiple glioblastomas. The time from onset of symptoms to death was approximately one year.", "contents": "Gliobastoma multiforme of the cerebellum. Glioblastoma multiforme of the cerebellum is rare. Approximately 33 case of cerebellar glioblastoma have been reported. Two-thirds of the cases occurred in adults and the male to female ratio was 2:1. The mean age was 46.7 years in adults and 10.4 years in children. Most of the tumors were lateral in location. Two of the patients (6%) had multiple glioblastomas. The time from onset of symptoms to death was approximately one year."} {"id": "PMID:167466", "title": "A survey of asthma mortality in patients between ages 35 and 64 in the Greater London hospitals in 1971.", "content": "We have examined the death certificates from all patients aged 35-64 years who were recorded as dying from asthma in Greater London Council hospitals in 1971. Of the 47 death certificates studied, nine suggested that the primary cause of death was not asthma. From the remaining 38 deaths we have obtained 36 case records and found that 15 deaths occurred outside hospital and another two patients died in hospital having been admitted in a stable state. We have examined the remaining 19 case records to find out the circumstances of death in patients with asthma who die in hospital. We have been unable to exclude the possibility that many of the deaths in hospital were avoidable. Assessment of severity in most patients was incomplete, as judged by a retrospective analysis of case records, and many of the patients would be regarded as having had insufficient treatment. Four patients did not receive corticosteroids and in a further three the dose given was small. No physiological assessment of airflow obstruction was made in over half the patients. A comparison with 19 survivors of an admission to hospital with asthma did not provide enough information to account for the deaths. The survivors were in hospital for a shorter period of time, were slightly less ill, and were given comparable treatment regimens. Both groups of patients were inadequately assessed, and sedatives were given to approximately 70% of all subjects studied. The deaths in hospital usually occurred suddenly in the early morning in general medical wards.", "contents": "A survey of asthma mortality in patients between ages 35 and 64 in the Greater London hospitals in 1971. We have examined the death certificates from all patients aged 35-64 years who were recorded as dying from asthma in Greater London Council hospitals in 1971. Of the 47 death certificates studied, nine suggested that the primary cause of death was not asthma. From the remaining 38 deaths we have obtained 36 case records and found that 15 deaths occurred outside hospital and another two patients died in hospital having been admitted in a stable state. We have examined the remaining 19 case records to find out the circumstances of death in patients with asthma who die in hospital. We have been unable to exclude the possibility that many of the deaths in hospital were avoidable. Assessment of severity in most patients was incomplete, as judged by a retrospective analysis of case records, and many of the patients would be regarded as having had insufficient treatment. Four patients did not receive corticosteroids and in a further three the dose given was small. No physiological assessment of airflow obstruction was made in over half the patients. A comparison with 19 survivors of an admission to hospital with asthma did not provide enough information to account for the deaths. The survivors were in hospital for a shorter period of time, were slightly less ill, and were given comparable treatment regimens. Both groups of patients were inadequately assessed, and sedatives were given to approximately 70% of all subjects studied. The deaths in hospital usually occurred suddenly in the early morning in general medical wards."} {"id": "PMID:167468", "title": "Ultrastructural pathology of leaf cells of ryegrass (Lolium multiflorum) infected with ryegrass mosaic virus.", "content": "Ryegrass mosaic virus particles and virus induced lamellar inclusions were found in mesophyll and epidermal cells of virus infected ryegrass leaves. The lamellar inclusions were occasionally found in phloem cells also. Virus particles occurred in cytoplasm, inside plasmodesmata and often in membrane bound sacs embedded in a matrix between plasmalemma and cell wall at or near plasmodesmata. Electron dense plugs protruding from plasmodesmata, finger-like cell wall outgrowths and cell wall deposits usually at plasmodesmata were also observed. Cytopathological changes in organelles in infected cells included dense deposits in the cisternae of endosplasmic reticulum and Golgi apparatus, mitochondria with electron-dense or opaque matrix, proliferating cristae and deteriorating unit membrane; and disintegrating chloroplasts.", "contents": "Ultrastructural pathology of leaf cells of ryegrass (Lolium multiflorum) infected with ryegrass mosaic virus. Ryegrass mosaic virus particles and virus induced lamellar inclusions were found in mesophyll and epidermal cells of virus infected ryegrass leaves. The lamellar inclusions were occasionally found in phloem cells also. Virus particles occurred in cytoplasm, inside plasmodesmata and often in membrane bound sacs embedded in a matrix between plasmalemma and cell wall at or near plasmodesmata. Electron dense plugs protruding from plasmodesmata, finger-like cell wall outgrowths and cell wall deposits usually at plasmodesmata were also observed. Cytopathological changes in organelles in infected cells included dense deposits in the cisternae of endosplasmic reticulum and Golgi apparatus, mitochondria with electron-dense or opaque matrix, proliferating cristae and deteriorating unit membrane; and disintegrating chloroplasts."} {"id": "PMID:167469", "title": "Structure and development of P-protein in phloem parenchyma and companion cells of legumes.", "content": "Phloem parenchyma and companion cells from four species of legumes, Phaseolus vulgaris L., Melilotus alba Desr., Desmodium canadense, L. and Dolichos lablab L., were examined electron microscopically to estabish the presence, structure and development of P-protein. P-protein components consisting of granular, fibrillar, tubular or crystalline structures were found in parenchyma cells of all species and in companion cells of M. alba. The earliest stages of P-protein formation were closely associated with dictyosome cisternae, dictyosome vesicles and/or spiny vesicles. After their formation, the P-protein bodies were frequently transformed into one or more structurally different components. Although these components appeared to be develop-mentally related, their specific associations and transformations differed in each species examined.", "contents": "Structure and development of P-protein in phloem parenchyma and companion cells of legumes. Phloem parenchyma and companion cells from four species of legumes, Phaseolus vulgaris L., Melilotus alba Desr., Desmodium canadense, L. and Dolichos lablab L., were examined electron microscopically to estabish the presence, structure and development of P-protein. P-protein components consisting of granular, fibrillar, tubular or crystalline structures were found in parenchyma cells of all species and in companion cells of M. alba. The earliest stages of P-protein formation were closely associated with dictyosome cisternae, dictyosome vesicles and/or spiny vesicles. After their formation, the P-protein bodies were frequently transformed into one or more structurally different components. Although these components appeared to be develop-mentally related, their specific associations and transformations differed in each species examined."} {"id": "PMID:167470", "title": "Structural and functional dynamics of oogenesis in Glossina austeni: general features, previtellogenesis and nurse cells.", "content": "Glossina austeni oogenesis throughout its nine-day pregnancy cycle is described with the focus on previtellogenic stages. The ultrastructural details of the oocyte-nurse cell relationship and cyst formation is presented. The oocyte develops in a syncytial association with 15 nurse cells with the entire unit surrounded by a follicular epithelium. The nurse cells have large elaborate nucleoli. Evidence of nuclear emissions and the presence of an unusual cytoplasmic membrane association were found. A variety of nuclear inclusions are seen in the oocyte. Glycogen, lipid, ribosomes and membrane organelles accumulate in the oocyte during previtellogenesis.", "contents": "Structural and functional dynamics of oogenesis in Glossina austeni: general features, previtellogenesis and nurse cells. Glossina austeni oogenesis throughout its nine-day pregnancy cycle is described with the focus on previtellogenic stages. The ultrastructural details of the oocyte-nurse cell relationship and cyst formation is presented. The oocyte develops in a syncytial association with 15 nurse cells with the entire unit surrounded by a follicular epithelium. The nurse cells have large elaborate nucleoli. Evidence of nuclear emissions and the presence of an unusual cytoplasmic membrane association were found. A variety of nuclear inclusions are seen in the oocyte. Glycogen, lipid, ribosomes and membrane organelles accumulate in the oocyte during previtellogenesis."} {"id": "PMID:167471", "title": "The histology and fine structure of the olfactory organ of the squid Lolliguncula brevis Blainville.", "content": "The olfactory organ of the squid has a thick, pseudostratified epithelium containing five morphological types of ciliated receptors. In the simplest receptors the cilia originate separately in the distal pole of the cell. All other receptors have some type of cilia filled cavity, varying from a simple pocket of cilia at the surface to a completely closed vesicle filled with cilia in cells deep in the epithelium. The receptors are compared to cells in the rhinophore of Nautilus and the olfactory organs of coleoid cephalopods. Possible functions of the olfactory organ, based on its morphology, are discussed.", "contents": "The histology and fine structure of the olfactory organ of the squid Lolliguncula brevis Blainville. The olfactory organ of the squid has a thick, pseudostratified epithelium containing five morphological types of ciliated receptors. In the simplest receptors the cilia originate separately in the distal pole of the cell. All other receptors have some type of cilia filled cavity, varying from a simple pocket of cilia at the surface to a completely closed vesicle filled with cilia in cells deep in the epithelium. The receptors are compared to cells in the rhinophore of Nautilus and the olfactory organs of coleoid cephalopods. Possible functions of the olfactory organ, based on its morphology, are discussed."} {"id": "PMID:167472", "title": "Morphological variations in gap junctions of ovarian granulosa cells.", "content": "Granulosa cells in ovarian follicles of rat, mouse, rabbit and hamster were studied by lanthanum tracer and freeze-fracture techniques. Abundant gap junctions exhibited striking intraspecific variation in size and pattern of particle aggregation. The smaller gap junctions showed close packing of the intramembranous A face particles. In large gap junctions, ranging up to 6 mu in diameter, particles were packed in rectilinear arrays separated by a labyrinthine network of particle-free 'aisles'. Small clusters of particles in a particle-poor circumferential zone suggested enlargement of junctions by peripheral accretion. Linear intramembranous structures, resembling those of occluding junctions, occasionally bounded large gap junctions. Spherical intracytoplasmic structures limited by gap junctional membranes were shown by tracer studies to arise by invagination of the cell surface. These were intrepreted as a means of disposal of junctions by interiorization.", "contents": "Morphological variations in gap junctions of ovarian granulosa cells. Granulosa cells in ovarian follicles of rat, mouse, rabbit and hamster were studied by lanthanum tracer and freeze-fracture techniques. Abundant gap junctions exhibited striking intraspecific variation in size and pattern of particle aggregation. The smaller gap junctions showed close packing of the intramembranous A face particles. In large gap junctions, ranging up to 6 mu in diameter, particles were packed in rectilinear arrays separated by a labyrinthine network of particle-free 'aisles'. Small clusters of particles in a particle-poor circumferential zone suggested enlargement of junctions by peripheral accretion. Linear intramembranous structures, resembling those of occluding junctions, occasionally bounded large gap junctions. Spherical intracytoplasmic structures limited by gap junctional membranes were shown by tracer studies to arise by invagination of the cell surface. These were intrepreted as a means of disposal of junctions by interiorization."} {"id": "PMID:167473", "title": "Responsiveness of urinary cyclic AMP and phosphate to parathyroid extract in patients with parathyroid disorders.", "content": "Responsiveness of urinary cyclic AMP and phosphate to 200 units of parathyroid extract was evaluated in 5 normal subjects, 2 patients with idiopathic hypoparathyroidism, 4 patients with pseudohypoparathyroidism and 3 patients with primary hyperparathyroidism. Among them, 3 patients with pseudohypoparathyroidism were examined prior to and during therapy with vitamin D. Two patients with primary hyperparathyroidism were examined before and after removal of adenomas. In control subjects, percent increase in cyclic AMP after parathyroid extract administration was 7265 plus or minus 3312%, and in phosphate 290 plus or minus 72%. It was found that in idiopathic hypoparathyroidism the response of cyclic AMP was in the normal range, though that of phosphate was higher than normal. In pseudohypoparathyroidism, as distinguished from what Drezner et al. called pseudohypoparathyroidism type II, the response of cyclic AMP was uniformly low, while that of phosphate was variable. Similar results were obtained during treatment with vitamin D. In primary hyperparathyroidism, the responses of both cyclic AMP and phosphate were lower than normal. After removal of adenomas, the response of phosphate became norma., but the response of cyclic AMP rose to a subnormal level in one patient, and remained low in the other. For the diagnosis of pseudohypoparathyroidism, the response in cyclic AMP was considered to be a more reliable index than that in phosphate whether the patient was being treated with vitamin D or not.", "contents": "Responsiveness of urinary cyclic AMP and phosphate to parathyroid extract in patients with parathyroid disorders. Responsiveness of urinary cyclic AMP and phosphate to 200 units of parathyroid extract was evaluated in 5 normal subjects, 2 patients with idiopathic hypoparathyroidism, 4 patients with pseudohypoparathyroidism and 3 patients with primary hyperparathyroidism. Among them, 3 patients with pseudohypoparathyroidism were examined prior to and during therapy with vitamin D. Two patients with primary hyperparathyroidism were examined before and after removal of adenomas. In control subjects, percent increase in cyclic AMP after parathyroid extract administration was 7265 plus or minus 3312%, and in phosphate 290 plus or minus 72%. It was found that in idiopathic hypoparathyroidism the response of cyclic AMP was in the normal range, though that of phosphate was higher than normal. In pseudohypoparathyroidism, as distinguished from what Drezner et al. called pseudohypoparathyroidism type II, the response of cyclic AMP was uniformly low, while that of phosphate was variable. Similar results were obtained during treatment with vitamin D. In primary hyperparathyroidism, the responses of both cyclic AMP and phosphate were lower than normal. After removal of adenomas, the response of phosphate became norma., but the response of cyclic AMP rose to a subnormal level in one patient, and remained low in the other. For the diagnosis of pseudohypoparathyroidism, the response in cyclic AMP was considered to be a more reliable index than that in phosphate whether the patient was being treated with vitamin D or not."} {"id": "PMID:167476", "title": "Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs.", "content": "Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made.", "contents": "Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs. Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made."} {"id": "PMID:167477", "title": "Androgen receptor in nuclei of rat testis.", "content": "Testis nuclei of hypophysectomized rats selectively accumulate labeled testosterone and 5alpha-dihydrotestosterone following the injection of tritiated testosterone in vivo. Testosterone and 5alpha-dihydrotestosterone are bound to macromolecules in nuclei and can be extracted with 0.5 M KCl. Accumulation of protein bound radioactive androgens in nuclei of isolated seminiferous tubules is similar to that of whole testis. The relative amounts of testosterone and dihydrotestosterone in purified nuclei were similar to the relative amounts bound to cytoplasmic receptors, suggesting that cytoplasmic androgen-receptor complexes may be transported into the nuclei. Binding of labeled androgen is saturable and inhibited by prior injection of unlabeled testosterone or cyproterone acetate. Nuclear binding sites are destroyed by the proteolytic enzyme pronase, but not by DNase. Like the cytoplasmic androgen-receptor complexes in rat testis, nuclear androgen-protein complexes are heat labile and dissociate slowly at 0 degrees C. androgens fail to accumulate in testis nuclei of the Stanley-Gumbreck androgen insensitive rat, a species lacking cytoplasmic androgen receptors in testis and other androgen target tissues.", "contents": "Androgen receptor in nuclei of rat testis. Testis nuclei of hypophysectomized rats selectively accumulate labeled testosterone and 5alpha-dihydrotestosterone following the injection of tritiated testosterone in vivo. Testosterone and 5alpha-dihydrotestosterone are bound to macromolecules in nuclei and can be extracted with 0.5 M KCl. Accumulation of protein bound radioactive androgens in nuclei of isolated seminiferous tubules is similar to that of whole testis. The relative amounts of testosterone and dihydrotestosterone in purified nuclei were similar to the relative amounts bound to cytoplasmic receptors, suggesting that cytoplasmic androgen-receptor complexes may be transported into the nuclei. Binding of labeled androgen is saturable and inhibited by prior injection of unlabeled testosterone or cyproterone acetate. Nuclear binding sites are destroyed by the proteolytic enzyme pronase, but not by DNase. Like the cytoplasmic androgen-receptor complexes in rat testis, nuclear androgen-protein complexes are heat labile and dissociate slowly at 0 degrees C. androgens fail to accumulate in testis nuclei of the Stanley-Gumbreck androgen insensitive rat, a species lacking cytoplasmic androgen receptors in testis and other androgen target tissues."} {"id": "PMID:167479", "title": "Protamine-precipitated estrogen receptor: a solid-phase ligand exchange assay.", "content": "Cytoplasmic estrogen receptor can exist either free (R) or bound to estradiol-17beta (RE). Both forms can be precipitated from cytosols by protamine sulfate. After protamine precipitation R binds 3-H-estradiol-17beta quantitatively at either 0 degrees or 30 degrees, while precipitated RE binds 3-H-estradiol-17beta only at 30 degrees by exchanging with previously bound hormone. Using these observations, we have developed a method for separate determination of both cytoplasmic R and RE. This method should also be applicable for assay of other steroid receptors, especially in cases where interfering components are present in the whole cytosol.", "contents": "Protamine-precipitated estrogen receptor: a solid-phase ligand exchange assay. Cytoplasmic estrogen receptor can exist either free (R) or bound to estradiol-17beta (RE). Both forms can be precipitated from cytosols by protamine sulfate. After protamine precipitation R binds 3-H-estradiol-17beta quantitatively at either 0 degrees or 30 degrees, while precipitated RE binds 3-H-estradiol-17beta only at 30 degrees by exchanging with previously bound hormone. Using these observations, we have developed a method for separate determination of both cytoplasmic R and RE. This method should also be applicable for assay of other steroid receptors, especially in cases where interfering components are present in the whole cytosol."} {"id": "PMID:167480", "title": "Dual infections of mice: visceral larva migrans and sublethal infection with Japanese encephalitis virus.", "content": "Experiments in 3 weeks old albino mice with Toxocara canis and sublethal infection with JE virus established a marked synergestic effect in dually infected mice. The results are discussed to indicate the possible role of visceral larva migrans in creating exploxive outbreaks of \"acute encephalopathy syndrome\" in individuals having simultaneous infection with a virus (es) which, alone, might produce only mild illness. The nature of the possible mechanisms involved yet remains to be understood.", "contents": "Dual infections of mice: visceral larva migrans and sublethal infection with Japanese encephalitis virus. Experiments in 3 weeks old albino mice with Toxocara canis and sublethal infection with JE virus established a marked synergestic effect in dually infected mice. The results are discussed to indicate the possible role of visceral larva migrans in creating exploxive outbreaks of \"acute encephalopathy syndrome\" in individuals having simultaneous infection with a virus (es) which, alone, might produce only mild illness. The nature of the possible mechanisms involved yet remains to be understood."} {"id": "PMID:167481", "title": "[DNA-, RNA-, lipidsynthesis and the specific activity of the glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in the different morphologic stages of Plasmodium vinckei].", "content": "DNA-, RNA-, and lipidsynthesis, glucose-6-phosphate-dehydrogenase, glucose-6-phosphatase and succinate-dehydrogenase were studied in the different morphologic stages of blood schizogony of Plasmodium vinckei. For the separation of these stages of the maturation cycle a discontinuous Ficoll-density gradient was developed. By this method the morphologic stages were separated and obtained in sufficient amounts. DNA-, RNA- and lipidsynthesis was not continuous in the intraerythrocytic cycle of the parasite. The glucose-6-phosphate dehydrogenase activity of the infected erythrocytes decreases whereas that of the glucose-6-phosphatase increases in the maturation cycle of P. vinckei.", "contents": "[DNA-, RNA-, lipidsynthesis and the specific activity of the glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in the different morphologic stages of Plasmodium vinckei]. DNA-, RNA-, and lipidsynthesis, glucose-6-phosphate-dehydrogenase, glucose-6-phosphatase and succinate-dehydrogenase were studied in the different morphologic stages of blood schizogony of Plasmodium vinckei. For the separation of these stages of the maturation cycle a discontinuous Ficoll-density gradient was developed. By this method the morphologic stages were separated and obtained in sufficient amounts. DNA-, RNA- and lipidsynthesis was not continuous in the intraerythrocytic cycle of the parasite. The glucose-6-phosphate dehydrogenase activity of the infected erythrocytes decreases whereas that of the glucose-6-phosphatase increases in the maturation cycle of P. vinckei."} {"id": "PMID:167483", "title": "[Morphologic, biochemical and functional properties of the mitochondria of the rabbit gastric mucosa].", "content": "Purified fractions of the rabbit gastric mucosa and liver mitochondria were isolated. Electrone microscopy and functional studies of mitochondria showed the most intact mitochondria of gastric mucosa to be localized in gradient fractions of p=1.16-1.18, and those of the liver in fractions with p=1.19-1.20. The gastric mitochondria differed from the liver mitochondria by specific localization in oxyntic cells, abundance of crists, small matrix volume, presence of high respiratory control at lesser values of pH, high respiratory activity, great amount of cytochromes of electron transport chain in inner mitochondria membrane, two-fold excess of cytochroma a in relation to b and c, absence of b5 and by presence of great amount of phosphathydilaethanolamine and unsaturated fatty acids.", "contents": "[Morphologic, biochemical and functional properties of the mitochondria of the rabbit gastric mucosa]. Purified fractions of the rabbit gastric mucosa and liver mitochondria were isolated. Electrone microscopy and functional studies of mitochondria showed the most intact mitochondria of gastric mucosa to be localized in gradient fractions of p=1.16-1.18, and those of the liver in fractions with p=1.19-1.20. The gastric mitochondria differed from the liver mitochondria by specific localization in oxyntic cells, abundance of crists, small matrix volume, presence of high respiratory control at lesser values of pH, high respiratory activity, great amount of cytochromes of electron transport chain in inner mitochondria membrane, two-fold excess of cytochroma a in relation to b and c, absence of b5 and by presence of great amount of phosphathydilaethanolamine and unsaturated fatty acids."} {"id": "PMID:167489", "title": "Primary signet ring cell carcinoma of bladder exemplifying vesical epithelial multipotentiality.", "content": "The eighth reported case of primary signet ring cell carcinoma of the urinary bladder is described clinically and pathologically. It is unusual because of complete replacement of the transitional epithelium by squamous and glandular metaplasia. The latter was particularly striking, demonstrating \"normal\" colonic mucosa, cystitis glandularis, well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and the rare signet ring cell carcinoma variant. The possible origin of such changes is discussed.", "contents": "Primary signet ring cell carcinoma of bladder exemplifying vesical epithelial multipotentiality. The eighth reported case of primary signet ring cell carcinoma of the urinary bladder is described clinically and pathologically. It is unusual because of complete replacement of the transitional epithelium by squamous and glandular metaplasia. The latter was particularly striking, demonstrating \"normal\" colonic mucosa, cystitis glandularis, well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and the rare signet ring cell carcinoma variant. The possible origin of such changes is discussed."} {"id": "PMID:167490", "title": "Sarcoidosis and malakoplakia.", "content": "A case of malakoplakia in a patient with generalized sarcoidosis is reported. A discussion of the histologic and clinical characteristics is presented. This is the sixth case in the literature of concemitant malakoplakia and sarcoidosis. The suggestion is made that the two disorders may be related.", "contents": "Sarcoidosis and malakoplakia. A case of malakoplakia in a patient with generalized sarcoidosis is reported. A discussion of the histologic and clinical characteristics is presented. This is the sixth case in the literature of concemitant malakoplakia and sarcoidosis. The suggestion is made that the two disorders may be related."} {"id": "PMID:167491", "title": "Depressed in vitro aggregation of platelets of chronic hemodialysis patients (CHDP): a role for cyclic AMP.", "content": "1) On log-log-coordiantes a direct correlation has bee shown to exist between plasma cyclic AMP and plasma Cr levels. 2) hemodialysis results in a significant reduction in the arterial plasma cyclic AMP levels, but a return of plasma cyclic AMP to pre-dialysis levels is seen within 30 mins post-dialysis. 3) the dialyzer clearance of cyclic AMP, both in vitro and vivo, is commensurate with its M.W. 4) In vitro platelet aggregation responses, to ADP, EPI, and COLL are not influenced by PRP cell counts between 150,000 and 300,000/mm3. 5) the BT of NC and CHDP are not significantly different, indicating that the in vivo hemostatic properties of the CHDP are otherwise intact. 6)the CHDP have PVPC significantly lower than the NC, a finding commensurate with the usual mold thrombocytopenia of renal failure. 7)the aggreation responses of the CHDP to COLL and to both Lo and Hi concentrations of ADP and EPI are significantly less than those of the NC. 8)A statistically significant inverse correlation between aggregation response and plasma cyclic AMP is observed.", "contents": "Depressed in vitro aggregation of platelets of chronic hemodialysis patients (CHDP): a role for cyclic AMP. 1) On log-log-coordiantes a direct correlation has bee shown to exist between plasma cyclic AMP and plasma Cr levels. 2) hemodialysis results in a significant reduction in the arterial plasma cyclic AMP levels, but a return of plasma cyclic AMP to pre-dialysis levels is seen within 30 mins post-dialysis. 3) the dialyzer clearance of cyclic AMP, both in vitro and vivo, is commensurate with its M.W. 4) In vitro platelet aggregation responses, to ADP, EPI, and COLL are not influenced by PRP cell counts between 150,000 and 300,000/mm3. 5) the BT of NC and CHDP are not significantly different, indicating that the in vivo hemostatic properties of the CHDP are otherwise intact. 6)the CHDP have PVPC significantly lower than the NC, a finding commensurate with the usual mold thrombocytopenia of renal failure. 7)the aggreation responses of the CHDP to COLL and to both Lo and Hi concentrations of ADP and EPI are significantly less than those of the NC. 8)A statistically significant inverse correlation between aggregation response and plasma cyclic AMP is observed."} {"id": "PMID:167493", "title": "Studies on the effects of hemodialysis on plasma lipoproteins.", "content": "Plasma Lps of the patients on maintenance hemodialysis and the patients with other specific renal diseases have been studied. The patients on hemodialysis frequently showed gross abnormality in their plasma Lps, which was differentiated from the abnormalities demonstrated in other renal diseases or clinical entities. An exception was type-III hyperlipoproteinemia; i.e. Lp electrophoretograms of the hemodialysis patients resembled those ultracentrifugal fractions had been made had VLDL of beta-migration in paper electrophoresis and another had VLDL or pre-beta-migration. During hemodialysis, intravascular lipolysis, accelerated by heparin infusion, affected all plasma Lps, producing an increase of alpha-Lps and cholestrol ester-rich-beta-Lp. The accelerated triglyceride hydrolysis under circumstances of high glucose availability may stimulate resynthesis of endogenous triglyceriderich Lps, which characterizes the plasma Lp abnormality in more than half of the hemodialysis patients. The abnormality may not be attribuate to the predisposing renal disease but due to an accumlation of the characteristic Lp during the course of maintenace hemodialysis. A possible cause of accelerated atherosclerosis in the hemodialysis patients may be the accumulation of remnants of plasma Lp catabolism and the stimulated synthesis of triglycerdie-rich plasma Lp.", "contents": "Studies on the effects of hemodialysis on plasma lipoproteins. Plasma Lps of the patients on maintenance hemodialysis and the patients with other specific renal diseases have been studied. The patients on hemodialysis frequently showed gross abnormality in their plasma Lps, which was differentiated from the abnormalities demonstrated in other renal diseases or clinical entities. An exception was type-III hyperlipoproteinemia; i.e. Lp electrophoretograms of the hemodialysis patients resembled those ultracentrifugal fractions had been made had VLDL of beta-migration in paper electrophoresis and another had VLDL or pre-beta-migration. During hemodialysis, intravascular lipolysis, accelerated by heparin infusion, affected all plasma Lps, producing an increase of alpha-Lps and cholestrol ester-rich-beta-Lp. The accelerated triglyceride hydrolysis under circumstances of high glucose availability may stimulate resynthesis of endogenous triglyceriderich Lps, which characterizes the plasma Lp abnormality in more than half of the hemodialysis patients. The abnormality may not be attribuate to the predisposing renal disease but due to an accumlation of the characteristic Lp during the course of maintenace hemodialysis. A possible cause of accelerated atherosclerosis in the hemodialysis patients may be the accumulation of remnants of plasma Lp catabolism and the stimulated synthesis of triglycerdie-rich plasma Lp."} {"id": "PMID:167495", "title": "Protective effect of modified silica gel fraction (MSGF) on the storage of canine liver for transplantation.", "content": "MSGF protects the function of canine ischemic (20mins) liver stored for 14 hrs. No significant liver protection, from irreversible damage, in dogs transplanted with ischemic livers, flushed with Ringer's lactate, Collins' solution, Sacks' solution or SGF before hypothermic storage was noted. Sacks' solution, although consistently better than Ringer's lactate and similiar to Collins' solution and SGF, was not half as good as MSGF.", "contents": "Protective effect of modified silica gel fraction (MSGF) on the storage of canine liver for transplantation. MSGF protects the function of canine ischemic (20mins) liver stored for 14 hrs. No significant liver protection, from irreversible damage, in dogs transplanted with ischemic livers, flushed with Ringer's lactate, Collins' solution, Sacks' solution or SGF before hypothermic storage was noted. Sacks' solution, although consistently better than Ringer's lactate and similiar to Collins' solution and SGF, was not half as good as MSGF."} {"id": "PMID:167500", "title": "[Comparison of the sensitivity of laboratory animals and tissue cultures to infection with Aujeszky's disease virus].", "content": "In mice and guinea-pigs high susceptibility was demonstrated following i. c. administration of the virus, approximately equalling to that of rabbits and tissue cultures. Also a relatively high susceptibility of guinea-pigs was demonstrated, with very distinct clinical symptoms of the disease, as compared with mice and rats after the other manners of infection. On the basis of the results obtained white mice were utilized for routine diagnostic of Aujeszky disease. After i. c. administration of positive, virus-containing material encephalitis develops with a rapid exitus occurring 12-24 hours earlier than in the rabbits. In brain tissue antigen was always demonstrated by immunofluorescence examination. Along with the biological experiment replicas of pig organs were examined by immunofluorescence method. Maximum of positive yellow-green fluorescence is found in the cytoplasma of epithelial tonsillar cells, sporadically in the cell nuclei. Epithelial cells are deformed according to the infection degree. The amount of antigen in the brain tissue is not so pronounced as in the tonsillar tissue, yet in animals with clinical pathological symptoms the antigen was always demonstrated.", "contents": "[Comparison of the sensitivity of laboratory animals and tissue cultures to infection with Aujeszky's disease virus]. In mice and guinea-pigs high susceptibility was demonstrated following i. c. administration of the virus, approximately equalling to that of rabbits and tissue cultures. Also a relatively high susceptibility of guinea-pigs was demonstrated, with very distinct clinical symptoms of the disease, as compared with mice and rats after the other manners of infection. On the basis of the results obtained white mice were utilized for routine diagnostic of Aujeszky disease. After i. c. administration of positive, virus-containing material encephalitis develops with a rapid exitus occurring 12-24 hours earlier than in the rabbits. In brain tissue antigen was always demonstrated by immunofluorescence examination. Along with the biological experiment replicas of pig organs were examined by immunofluorescence method. Maximum of positive yellow-green fluorescence is found in the cytoplasma of epithelial tonsillar cells, sporadically in the cell nuclei. Epithelial cells are deformed according to the infection degree. The amount of antigen in the brain tissue is not so pronounced as in the tonsillar tissue, yet in animals with clinical pathological symptoms the antigen was always demonstrated."} {"id": "PMID:167503", "title": "Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer.", "content": "After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock.", "contents": "Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer. After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock."} {"id": "PMID:167504", "title": "Newer knowledge in comparative virology--its contribution to human health research.", "content": "Like other comparative sciences, and despite its recent beginning comparative virology has already contributed useful applications and observations to human health research. Teachings derived from the study of Marek's disease found application in that of Burkitt's lymphoma, and may lead to a possible vaccine against the human disease. Equally useful information came from the study of canine distemper in the development of a chorio-allantoic membrane attenuated measles vaccine, and in our knowledge of subacute sclerosing panencephalitis (SSPE) of humans; from the study of reovirus-like agents of infant mice and neonatal calves in that of an acute nonbacterial gastro-enteritis of infants and young children; and from that of the cancer-producing viruses of chickens, cats, and dogs to a better understanding of some human neoplasias. Finally, Aleutian mink disease may be an excellent natural model for the study of the collagen diseases of man, and scrapie of sheep one for that of a human chronic degenerative disease of the central nervous system of humans such as Kuru. Comparative virology has proved quite productive in a relatively short period, and is unlikely to be neglected in the future.", "contents": "Newer knowledge in comparative virology--its contribution to human health research. Like other comparative sciences, and despite its recent beginning comparative virology has already contributed useful applications and observations to human health research. Teachings derived from the study of Marek's disease found application in that of Burkitt's lymphoma, and may lead to a possible vaccine against the human disease. Equally useful information came from the study of canine distemper in the development of a chorio-allantoic membrane attenuated measles vaccine, and in our knowledge of subacute sclerosing panencephalitis (SSPE) of humans; from the study of reovirus-like agents of infant mice and neonatal calves in that of an acute nonbacterial gastro-enteritis of infants and young children; and from that of the cancer-producing viruses of chickens, cats, and dogs to a better understanding of some human neoplasias. Finally, Aleutian mink disease may be an excellent natural model for the study of the collagen diseases of man, and scrapie of sheep one for that of a human chronic degenerative disease of the central nervous system of humans such as Kuru. Comparative virology has proved quite productive in a relatively short period, and is unlikely to be neglected in the future."} {"id": "PMID:167510", "title": "Lipidosislike renal changes in rats treated with chlorphentermine or with tricyclic antidepressants.", "content": "Histological, histochemical and ultrastructural examinations were performed on renal tissues of rats after prolonged oral administration of the anorectic drug chlorphentermine or of the tricyclic antidepressants iprindole, imipramine and clomipramine. All drugs caused the formation of multilamellated cytoplasmic inclusions throughout the nephron and the collecting duct system, and in interstitial cells. The cytological alterations were most prominent in the glomerular podocytes, in the proximal convoluted tubules, and in the collecting duct system. In view of the histochemical properties (staining with Baker's acid hematein) and the ultrastructural appearance of the cytoplasmic inclusions the cellular alterations are interpreted as a renal manifestation of a generalized lipidosis induced by drugs of amphiphilic character.", "contents": "Lipidosislike renal changes in rats treated with chlorphentermine or with tricyclic antidepressants. Histological, histochemical and ultrastructural examinations were performed on renal tissues of rats after prolonged oral administration of the anorectic drug chlorphentermine or of the tricyclic antidepressants iprindole, imipramine and clomipramine. All drugs caused the formation of multilamellated cytoplasmic inclusions throughout the nephron and the collecting duct system, and in interstitial cells. The cytological alterations were most prominent in the glomerular podocytes, in the proximal convoluted tubules, and in the collecting duct system. In view of the histochemical properties (staining with Baker's acid hematein) and the ultrastructural appearance of the cytoplasmic inclusions the cellular alterations are interpreted as a renal manifestation of a generalized lipidosis induced by drugs of amphiphilic character."} {"id": "PMID:167511", "title": "Intracytoplasmic granule-lamella structures in visceral epithelial cells of human glomeruli.", "content": "A description is given of the rare occurrence of peculiar oblong structures having a maximal length of about 4.5 micron and a width of 0.5 micron, in the visceral epithelial cells of human glomeruli. These inclusions are marked by regular arrangement of parallel lamellae which are either in parts or over their whole surface associated with ribosome-like particles. Besides speculations on their origin and nature, some literature data come up for discussion.", "contents": "Intracytoplasmic granule-lamella structures in visceral epithelial cells of human glomeruli. A description is given of the rare occurrence of peculiar oblong structures having a maximal length of about 4.5 micron and a width of 0.5 micron, in the visceral epithelial cells of human glomeruli. These inclusions are marked by regular arrangement of parallel lamellae which are either in parts or over their whole surface associated with ribosome-like particles. Besides speculations on their origin and nature, some literature data come up for discussion."} {"id": "PMID:167528", "title": "Biological age and habitual physical activity in relation to physical fitness in 12- and 13-year-old schoolboys.", "content": "The purpose of this study was to investigate the relationship between biological age, habitual physical activity and anthropometrical and physiological characteristics in 12- and 13-year-old schoolboys (n = 70). At the beginning and the end of the school year 1971/2 biological age was determined by measuring skeletal age from left hand X-ray photographs. Habitual physical activity was determined by questionnaire interview and pedometers. All anthropometrical characteristics showed significant correlations (P less than 0.05) with skeletal age except for bicipital and tricipital skinfolds. Out of 9 physical fitness tests handgrip was the only test that showed a significant correlation (0.52) with skeletal age. Pedometer scores gave significant negative correlations (P less than 0.05) with anthropometrical characteristics except for tricipital skinfold. The fitness tests bent arm hang, 12 min run walk, sit and reach and W-170 showed significant correlations (P less than 0.05) with pedometer scores.", "contents": "Biological age and habitual physical activity in relation to physical fitness in 12- and 13-year-old schoolboys. The purpose of this study was to investigate the relationship between biological age, habitual physical activity and anthropometrical and physiological characteristics in 12- and 13-year-old schoolboys (n = 70). At the beginning and the end of the school year 1971/2 biological age was determined by measuring skeletal age from left hand X-ray photographs. Habitual physical activity was determined by questionnaire interview and pedometers. All anthropometrical characteristics showed significant correlations (P less than 0.05) with skeletal age except for bicipital and tricipital skinfolds. Out of 9 physical fitness tests handgrip was the only test that showed a significant correlation (0.52) with skeletal age. Pedometer scores gave significant negative correlations (P less than 0.05) with anthropometrical characteristics except for tricipital skinfold. The fitness tests bent arm hang, 12 min run walk, sit and reach and W-170 showed significant correlations (P less than 0.05) with pedometer scores."} {"id": "PMID:167530", "title": "Size and distribution of SV 40 DNA Sequences covalently linked with the DNA of permissive mammalian cells.", "content": "CV-1 cells productively infected with SV 40 contain viral DNA which is covalently linked with the host cell DNA. These linear duplex viral-host DNA molecules are replicated during the infectious cycle. They can be selectively isolated and purified by two successive cycles of DNA-DNA hybridization and elution steps using first CV-1 cell and then SV 40-DNA immobilized on filters. In an attempt to clarify the nature of the host DNA sequences neighbouring the viral DNA it was found that reiterated host DNA must be within the range of 800 bases from the viral sequences. Reassociation kinetics and treatment of the reassociated viral-host DNA sequences with single strand-specific S1 nuclease have shown that unique host DNA sequences are always present in close neighbourhood of the viral DNA. Most of the SV 40 DNA sequences are probably intergrated as fragments of subgenomic length.", "contents": "Size and distribution of SV 40 DNA Sequences covalently linked with the DNA of permissive mammalian cells. CV-1 cells productively infected with SV 40 contain viral DNA which is covalently linked with the host cell DNA. These linear duplex viral-host DNA molecules are replicated during the infectious cycle. They can be selectively isolated and purified by two successive cycles of DNA-DNA hybridization and elution steps using first CV-1 cell and then SV 40-DNA immobilized on filters. In an attempt to clarify the nature of the host DNA sequences neighbouring the viral DNA it was found that reiterated host DNA must be within the range of 800 bases from the viral sequences. Reassociation kinetics and treatment of the reassociated viral-host DNA sequences with single strand-specific S1 nuclease have shown that unique host DNA sequences are always present in close neighbourhood of the viral DNA. Most of the SV 40 DNA sequences are probably intergrated as fragments of subgenomic length."} {"id": "PMID:167531", "title": "[Xenotransplantation of established tumor cells in congenital thymusless \"nude\" mice (author's transl)].", "content": "Successful xenotransplantation of 5 different established tumor cell-lines was performed in the congenital thymusless mouse mutant \"nude\". The tumors were one human carcinoma of the cervix (HeLa), one Burkitt's lymphoma as well as two Polyoma virus-induced tumors from rats and one spontaneous tumor from hamster. During an observation period of 21-28 days all cells formed rapidly growing tumors at the injection site. The critical cell dose varied in the different lines between 10-4 and 10-6 cells. Histological appearance of the neoplasias resembled that of the primary tumors. Two established lines from normal fibroblasts (3-T-3) and kidney (CV-1) failed to grow. Our results indicate that xenotransplantation in \"nude\" mice may serve as a simple in-vivo assay for testing the oncogenicity of tissue culture cells.", "contents": "[Xenotransplantation of established tumor cells in congenital thymusless \"nude\" mice (author's transl)]. Successful xenotransplantation of 5 different established tumor cell-lines was performed in the congenital thymusless mouse mutant \"nude\". The tumors were one human carcinoma of the cervix (HeLa), one Burkitt's lymphoma as well as two Polyoma virus-induced tumors from rats and one spontaneous tumor from hamster. During an observation period of 21-28 days all cells formed rapidly growing tumors at the injection site. The critical cell dose varied in the different lines between 10-4 and 10-6 cells. Histological appearance of the neoplasias resembled that of the primary tumors. Two established lines from normal fibroblasts (3-T-3) and kidney (CV-1) failed to grow. Our results indicate that xenotransplantation in \"nude\" mice may serve as a simple in-vivo assay for testing the oncogenicity of tissue culture cells."} {"id": "PMID:167532", "title": "Respiratory activity of Ehrlich ascites tumour cell nuclei.", "content": "1. Intact Ehrlich ascites tumour cells exhibit a residual respiration which is insensitive to site-specific inhibitors of mitochrondrial electron transport. Treatment of the tumour-bearing mice with phenobarbital does not influence the rate of this inhibitor-resistant respiration. 2. Among the respiratory pigments analysed spectrophotometrically in the microsomal fraction prepared from ascites cells, only small amounts of flavoproteins (NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase) were detectable. 3. Ascites-cell nuclei respire with NADH or NADPH, but not with succinate, as substrates and the respiration is unaffected by inhibitors of mitochondrial electron and energy transfer. These nuclei contain cytochrome b5, whereas cytochrome P-450 or mitochondrial-like cytochromes are lacking. 4. It is concluded that the NAD(P)H-dependent electron transport in nuclei is responsible for the inhibitor-insensitive O2 uptake of intact cells. Conversely, mixed function oxidation reactions of the endoplasmic reticulum have no role in this connection. Moreover, it is assumed that nuclear respiration is involved in the control of the cellular redox potential. 5. The relevance of the data obtained with respect to some assumptions concerning the biogenesis of the endoplasmic reticulum is discussed.", "contents": "Respiratory activity of Ehrlich ascites tumour cell nuclei. 1. Intact Ehrlich ascites tumour cells exhibit a residual respiration which is insensitive to site-specific inhibitors of mitochrondrial electron transport. Treatment of the tumour-bearing mice with phenobarbital does not influence the rate of this inhibitor-resistant respiration. 2. Among the respiratory pigments analysed spectrophotometrically in the microsomal fraction prepared from ascites cells, only small amounts of flavoproteins (NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase) were detectable. 3. Ascites-cell nuclei respire with NADH or NADPH, but not with succinate, as substrates and the respiration is unaffected by inhibitors of mitochondrial electron and energy transfer. These nuclei contain cytochrome b5, whereas cytochrome P-450 or mitochondrial-like cytochromes are lacking. 4. It is concluded that the NAD(P)H-dependent electron transport in nuclei is responsible for the inhibitor-insensitive O2 uptake of intact cells. Conversely, mixed function oxidation reactions of the endoplasmic reticulum have no role in this connection. Moreover, it is assumed that nuclear respiration is involved in the control of the cellular redox potential. 5. The relevance of the data obtained with respect to some assumptions concerning the biogenesis of the endoplasmic reticulum is discussed."} {"id": "PMID:167533", "title": "The fine structure of the cysticercoid of Hymenolepis diminuta. III. The scolex.", "content": "Transmission electron microscopy of the scolex of the 8-day-old Hymenolepis diminuta cysticercoid demonstrates its resemblance to the scolex of the adult. A syncytial tegument composed of external and internal layers is connected by cytoplasmic extensions. Fully developed microtriches are present. Furthermore, a basement membrane, muscle layers, and medullary region containing flame cells, nerve tissue, and other cell bodies are observed. Of particular interest is the presence of discrete sensory endings whose function is discussed.", "contents": "The fine structure of the cysticercoid of Hymenolepis diminuta. III. The scolex. Transmission electron microscopy of the scolex of the 8-day-old Hymenolepis diminuta cysticercoid demonstrates its resemblance to the scolex of the adult. A syncytial tegument composed of external and internal layers is connected by cytoplasmic extensions. Fully developed microtriches are present. Furthermore, a basement membrane, muscle layers, and medullary region containing flame cells, nerve tissue, and other cell bodies are observed. Of particular interest is the presence of discrete sensory endings whose function is discussed."} {"id": "PMID:167535", "title": "Studies on the immunizing capacity of orally administered particulate antigens. I. The efficiency of killed Bordetella pertussis cells.", "content": "The single i.p. injection of 2.5 times 10-8 killed B. pertussis cells protected 23 out of a group of 24 NMRI mice (95.8%) against the subsequent intracerebral infection, whilst 13 out of 24 mice (54.2%) survived the intracerebral challenge with virulent B. pertussis cells after prior oral administration of 2.5 times 10-11 killed B. pertussis cells, as demonstrated by the mouse protection test. Similar treatment with non-specific substances, such as egg white and saline, did not result in any increase of resistance. Systemic anaphylactic hypersensitivity to bovine serum albumin could also be achieved, when either both the protein antigen and the B. pertussis vaccine were given by the oral route or when the B. pertussis vaccine was injected intraperitoneally into mice which had received the soluble protein antigen by the oral route. Such effects were not produced at all in the reverse situation, when the B. pertussis vaccine was orally administered in mice, which were given the soluble protein antigen by the intraperitoneal route. After oral inoculation of 6 times 10-11 killed B. pertussis cells neither splenomegaly nor blood lymphocytosis became detectable. It is still unknown, in which manner the orally administered B. pertussis vaccine effects protection against the intracerebral infection with virulent bacteria as well as susceptibility for systemic anaphylaxis. The data presented do not favor the view that those effects are due to the phenomenon of persorption.", "contents": "Studies on the immunizing capacity of orally administered particulate antigens. I. The efficiency of killed Bordetella pertussis cells. The single i.p. injection of 2.5 times 10-8 killed B. pertussis cells protected 23 out of a group of 24 NMRI mice (95.8%) against the subsequent intracerebral infection, whilst 13 out of 24 mice (54.2%) survived the intracerebral challenge with virulent B. pertussis cells after prior oral administration of 2.5 times 10-11 killed B. pertussis cells, as demonstrated by the mouse protection test. Similar treatment with non-specific substances, such as egg white and saline, did not result in any increase of resistance. Systemic anaphylactic hypersensitivity to bovine serum albumin could also be achieved, when either both the protein antigen and the B. pertussis vaccine were given by the oral route or when the B. pertussis vaccine was injected intraperitoneally into mice which had received the soluble protein antigen by the oral route. Such effects were not produced at all in the reverse situation, when the B. pertussis vaccine was orally administered in mice, which were given the soluble protein antigen by the intraperitoneal route. After oral inoculation of 6 times 10-11 killed B. pertussis cells neither splenomegaly nor blood lymphocytosis became detectable. It is still unknown, in which manner the orally administered B. pertussis vaccine effects protection against the intracerebral infection with virulent bacteria as well as susceptibility for systemic anaphylaxis. The data presented do not favor the view that those effects are due to the phenomenon of persorption."} {"id": "PMID:167536", "title": "Outbursting wedges of the colonies of Clostridium welchii containing chain forming mutants after ultra violet irradiation.", "content": "Cl. welchii NCTC 6785 was irradiated with UV light. The 40 minutes irradiated cells after 3-8 days ageing at room temperature (22-25 degrees C) and 48 hours initial incubation at 37 degrees C produced hairy outbursting wedges. These wedges gave rise to the colonies composed of chain forming mutants, which on transfer into the fluid medium grew into a pure chain forming culture.", "contents": "Outbursting wedges of the colonies of Clostridium welchii containing chain forming mutants after ultra violet irradiation. Cl. welchii NCTC 6785 was irradiated with UV light. The 40 minutes irradiated cells after 3-8 days ageing at room temperature (22-25 degrees C) and 48 hours initial incubation at 37 degrees C produced hairy outbursting wedges. These wedges gave rise to the colonies composed of chain forming mutants, which on transfer into the fluid medium grew into a pure chain forming culture."} {"id": "PMID:167537", "title": "[Pass-way of Epstein-Barr virus in the abortive infection of human lymphoid cells (author's transl)].", "content": "Biologically active, 3-H-thymidine-labeled Epstein-Barr virus has been purified by a method, specifically developed for these experiments, and used to infect the human lymphoid cell lines NC37 and Raji. At a late stage of this abortive infection (after 40 hr), 3-H-DNA has been recovered from the nuclei of the infected cells. This DNA has the density and size of free viral DNA. No evidence for integration was observed, in that less than 0,5 viral genome per cell had become covalently bound to cellular DNA. Simultaneously, the viral infection was studied by electron-microscopy.", "contents": "[Pass-way of Epstein-Barr virus in the abortive infection of human lymphoid cells (author's transl)]. Biologically active, 3-H-thymidine-labeled Epstein-Barr virus has been purified by a method, specifically developed for these experiments, and used to infect the human lymphoid cell lines NC37 and Raji. At a late stage of this abortive infection (after 40 hr), 3-H-DNA has been recovered from the nuclei of the infected cells. This DNA has the density and size of free viral DNA. No evidence for integration was observed, in that less than 0,5 viral genome per cell had become covalently bound to cellular DNA. Simultaneously, the viral infection was studied by electron-microscopy."} {"id": "PMID:167541", "title": "Water structure in striated muscle by spin labelling technique.", "content": "The electron paramagnetic resonance (epr) spectra of a nitroxide-type free radical (4-hydroxy-2,2,6,6-tetramethyl-piperidinooxyl, tempol) of equilibrated in muscle water were measured. The results were analyzed in terms of the correlation time or microviscosity. The correlation time of spin probe was only four-five times higher in muscle water than in physiological solutions. The mobility gradually decreased with decreasing relative water content, a restricted mobility having been observed at low relative water content (i equals 0.3) only. The experimental results can be interpreted without assuming the major part of water phase in striated muscle to be ice-like or semicrystalline.", "contents": "Water structure in striated muscle by spin labelling technique. The electron paramagnetic resonance (epr) spectra of a nitroxide-type free radical (4-hydroxy-2,2,6,6-tetramethyl-piperidinooxyl, tempol) of equilibrated in muscle water were measured. The results were analyzed in terms of the correlation time or microviscosity. The correlation time of spin probe was only four-five times higher in muscle water than in physiological solutions. The mobility gradually decreased with decreasing relative water content, a restricted mobility having been observed at low relative water content (i equals 0.3) only. The experimental results can be interpreted without assuming the major part of water phase in striated muscle to be ice-like or semicrystalline."} {"id": "PMID:167542", "title": "Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin.", "content": "Previous studies have revealed that the endothelial cells of cerebral vessels are linked by tight junctions preventing an intercellular passage of exogenous peroxidase. However, under normal conditions, vesicular transport of the tracer has been demonstrated in parts of cerebral vessels, especially in arterioles with a diameter of 30-100 mu. Solutions, containing 50-800 mug of buffered 5-hydroxytryptamine sulphate (serotonin), were perfused through the cerebral ventricles on mice after intravenous injection of horseradish peroxidase. Usually, the biogenic amine enhanced the vesicular transport of exogenous peroxidase. The serotonin-induced increased transport was observed in vessels on the surface of the brain as well as in vessels located in the parenchyma. No cell damage was observed. Increased transport was observed in arterioles, venules, and in capillaries. Therefore, it is not likely that the serotonin effect is a constriction of smooth muscle cells causing an opening of the tight junctions followed by an intercellular movement of tracer. The most reasonable assumption behind the mechanism is that serotonin affects the plasmamembrane of endothelial cells resulting in an enhanced production and transfer of cytoplasmic vesicles.", "contents": "Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin. Previous studies have revealed that the endothelial cells of cerebral vessels are linked by tight junctions preventing an intercellular passage of exogenous peroxidase. However, under normal conditions, vesicular transport of the tracer has been demonstrated in parts of cerebral vessels, especially in arterioles with a diameter of 30-100 mu. Solutions, containing 50-800 mug of buffered 5-hydroxytryptamine sulphate (serotonin), were perfused through the cerebral ventricles on mice after intravenous injection of horseradish peroxidase. Usually, the biogenic amine enhanced the vesicular transport of exogenous peroxidase. The serotonin-induced increased transport was observed in vessels on the surface of the brain as well as in vessels located in the parenchyma. No cell damage was observed. Increased transport was observed in arterioles, venules, and in capillaries. Therefore, it is not likely that the serotonin effect is a constriction of smooth muscle cells causing an opening of the tight junctions followed by an intercellular movement of tracer. The most reasonable assumption behind the mechanism is that serotonin affects the plasmamembrane of endothelial cells resulting in an enhanced production and transfer of cytoplasmic vesicles."} {"id": "PMID:167539", "title": "Clinical cytology of the liver.", "content": "A combined cytologic and histologic study of 149 needle-biopsy specimens of liver tissue was done. These specimens represented a wide range of normal and pathologic conditions. Malignancy was demonstrated in 27 cases--18 by both methods of study, one by histologic study alone, and eight by cytologic study alone. In the last group of eight, four were considered conclusive for malignancy and four were suspicious. These results confirm the findings of others who also report the advantages of combined cytologic and histologic study of needle-biopsy specimens for diagnosing malignancy. Similar results have been obtained with cytologic study of fine-needle aspirates. The commonly occurring cytologic findings in liver specimens are presented with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma.", "contents": "Clinical cytology of the liver. A combined cytologic and histologic study of 149 needle-biopsy specimens of liver tissue was done. These specimens represented a wide range of normal and pathologic conditions. Malignancy was demonstrated in 27 cases--18 by both methods of study, one by histologic study alone, and eight by cytologic study alone. In the last group of eight, four were considered conclusive for malignancy and four were suspicious. These results confirm the findings of others who also report the advantages of combined cytologic and histologic study of needle-biopsy specimens for diagnosing malignancy. Similar results have been obtained with cytologic study of fine-needle aspirates. The commonly occurring cytologic findings in liver specimens are presented with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma."} {"id": "PMID:167543", "title": "Calcium metabolism.", "content": "It is evident that in the past decade much new information has been gathered regarding calcium metabolism at the physiological and extracellular level. In addition, new information is becoming available regarding intracellular mechanisms of calcium transport and mobilization. Finally, during the past decade the hormone calcitonin has been introduced as well as a hormone derived from vitamin D, namely 1,25-(OH)2D3, has been discovered and demonstrated to play a central role in the regulation of calcium metabolism. The exciting developments will undoubtedly foster the revelation of new information during the next decade which hopefully will bring about an elucidation of the molecular mechanisms of calcium metabolism.", "contents": "Calcium metabolism. It is evident that in the past decade much new information has been gathered regarding calcium metabolism at the physiological and extracellular level. In addition, new information is becoming available regarding intracellular mechanisms of calcium transport and mobilization. Finally, during the past decade the hormone calcitonin has been introduced as well as a hormone derived from vitamin D, namely 1,25-(OH)2D3, has been discovered and demonstrated to play a central role in the regulation of calcium metabolism. The exciting developments will undoubtedly foster the revelation of new information during the next decade which hopefully will bring about an elucidation of the molecular mechanisms of calcium metabolism."} {"id": "PMID:167540", "title": "Cytologic detection of early Paget's disease of breast with improved cellular collection method.", "content": "Improved cellular collection method and cytologic criteria for diagnosis of Paget's disease of the breast are presented. When indicated, the cytologic test is highly recommended for the early detection and pre-operative diagnosis of the minimal breast cancer10.", "contents": "Cytologic detection of early Paget's disease of breast with improved cellular collection method. Improved cellular collection method and cytologic criteria for diagnosis of Paget's disease of the breast are presented. When indicated, the cytologic test is highly recommended for the early detection and pre-operative diagnosis of the minimal breast cancer10."} {"id": "PMID:167545", "title": "Renal tumours in children.", "content": "A ten-year series of renal tumours in children up to 14 years of age was collected from the files of the Finnish Cancer Register. After histological evaluation of the material, 74 cases were accepted as primary renal tumours. Fifty-eight of these were typical Wilms' tumours, three rhabdomyosarcomas, six foetal hamartomas and seven unclassified malignant tumours. Wilms' tumours were classified into three types on the basis of the histological differentiation. The total five year survival in the Wilms group was 50 per cent with no difference between patients over and under the age of one year. Of the subtypes of Wilms' tumours the sarcomatous type showed worse prognosis than average; only three out of 16 patients were alive after a five-year follow-up time. None of the patients with foetal hamartoma died of tumour, although two fatalities, connected with the surgery, were recorded. The value of histological classification of Wilms' tumours and the importance of the recognition of the foetal hamartoma is emphasized.", "contents": "Renal tumours in children. A ten-year series of renal tumours in children up to 14 years of age was collected from the files of the Finnish Cancer Register. After histological evaluation of the material, 74 cases were accepted as primary renal tumours. Fifty-eight of these were typical Wilms' tumours, three rhabdomyosarcomas, six foetal hamartomas and seven unclassified malignant tumours. Wilms' tumours were classified into three types on the basis of the histological differentiation. The total five year survival in the Wilms group was 50 per cent with no difference between patients over and under the age of one year. Of the subtypes of Wilms' tumours the sarcomatous type showed worse prognosis than average; only three out of 16 patients were alive after a five-year follow-up time. None of the patients with foetal hamartoma died of tumour, although two fatalities, connected with the surgery, were recorded. The value of histological classification of Wilms' tumours and the importance of the recognition of the foetal hamartoma is emphasized."} {"id": "PMID:167547", "title": "Carbon monoxide as a degradation product of cytochrome C and of ascorbic acid.", "content": "Cytochrome c has been incubated with 4 different reducing agents at 37 degrees C for 24 h at pH 7.0, and the spectral changes and the production of carbon monoxide have been followed. Only with hydrazine hydrate cytochrome c produced some carbon monoxide. Accidentally, carbon monoxide formation from ascorbic acid was found, amounting to about 0.1 mumol from 15 mumol of ascorbic acid in 24 h under the above conditions.", "contents": "Carbon monoxide as a degradation product of cytochrome C and of ascorbic acid. Cytochrome c has been incubated with 4 different reducing agents at 37 degrees C for 24 h at pH 7.0, and the spectral changes and the production of carbon monoxide have been followed. Only with hydrazine hydrate cytochrome c produced some carbon monoxide. Accidentally, carbon monoxide formation from ascorbic acid was found, amounting to about 0.1 mumol from 15 mumol of ascorbic acid in 24 h under the above conditions."} {"id": "PMID:167544", "title": "Degenerative changes in the human vestibular sensory epithelia.", "content": "A study of the vestibular end organs from humans of different ages is presented. The inner ears were exposed by microdissection, and the vestibular sensory regions were either sectioned and studied with light or electron microscopy, or prepared and studied with the surface specimen technique. A change, which can be related to aging, is the accumulation of lipofuscin inclusions in sensory and supporting cells, especially pronounced in the type I sensory cell. Changes of the hair bundles, such as disarrangement of cilia, increased fragility of cilia and formation of giant cilia, have also been observed in aged individuals. In three cases there was a history of vestibular disturbance of vertigo. All three cases had shown caloric hypo-reactivity. In two cases, one with a history of herpes zoster oticus and another with a brain stem glioma, no morphological changes which could be attributed to the diseases, were found. The third case showed degeneration of macula utriculi and the lateral and superior cristae, possibly as a result of vascular disturbance.", "contents": "Degenerative changes in the human vestibular sensory epithelia. A study of the vestibular end organs from humans of different ages is presented. The inner ears were exposed by microdissection, and the vestibular sensory regions were either sectioned and studied with light or electron microscopy, or prepared and studied with the surface specimen technique. A change, which can be related to aging, is the accumulation of lipofuscin inclusions in sensory and supporting cells, especially pronounced in the type I sensory cell. Changes of the hair bundles, such as disarrangement of cilia, increased fragility of cilia and formation of giant cilia, have also been observed in aged individuals. In three cases there was a history of vestibular disturbance of vertigo. All three cases had shown caloric hypo-reactivity. In two cases, one with a history of herpes zoster oticus and another with a brain stem glioma, no morphological changes which could be attributed to the diseases, were found. The third case showed degeneration of macula utriculi and the lateral and superior cristae, possibly as a result of vascular disturbance."} {"id": "PMID:167548", "title": "Rate limiting factors in sympathetic neurotransmitter secretion.", "content": "Isolated superfused field stimulated preparations of guinea-pig vas deferens, in which the neural stores of noradrenaline (NA) had been labelled by preincubation with tritium-marked (-)-NA, were used to study the factors regulating the amount of NA secreted from the nerves, per applied shock. The results indicate that \"Stimulation secretion coupling\" in this tissue is subject to 2 different kinds of facilitation, one independent and one dependent on nerve stimulation frequency. Kinetic analysis of the calcium dependence of transmitter secretion, after removal of alpha-adrenoceptor mediated negative feedback control, suggests that there is a definite upper limit to the amount of transmitter which can be secreted, per pulse, from each \"secretary area\" of the nerves. The low Q(10) value of this apparent V(maz) suggests that the rate limiting factor is non-enzymatic in nature. It is proposed that the ultimately rate limiting factor in NA secretion may rather be the number of vesicles in each potential \"secretary area\" which are in a suitable position within the nerve for active participation in the secretion of transmitter.", "contents": "Rate limiting factors in sympathetic neurotransmitter secretion. Isolated superfused field stimulated preparations of guinea-pig vas deferens, in which the neural stores of noradrenaline (NA) had been labelled by preincubation with tritium-marked (-)-NA, were used to study the factors regulating the amount of NA secreted from the nerves, per applied shock. The results indicate that \"Stimulation secretion coupling\" in this tissue is subject to 2 different kinds of facilitation, one independent and one dependent on nerve stimulation frequency. Kinetic analysis of the calcium dependence of transmitter secretion, after removal of alpha-adrenoceptor mediated negative feedback control, suggests that there is a definite upper limit to the amount of transmitter which can be secreted, per pulse, from each \"secretary area\" of the nerves. The low Q(10) value of this apparent V(maz) suggests that the rate limiting factor is non-enzymatic in nature. It is proposed that the ultimately rate limiting factor in NA secretion may rather be the number of vesicles in each potential \"secretary area\" which are in a suitable position within the nerve for active participation in the secretion of transmitter."} {"id": "PMID:167549", "title": "Effects on the ventral spinocerebellar tract neurones from Deiters' nucleus and the medial longitudinal fascicle in the cat.", "content": "Effects from the vestibulospinal tract (VST) and from fibres descending in the medial longitudinal fascicle (MLF) on the cells of origin of the ventral spinocerebellar tract (VSCT) have been studied with intracellular recording. Out of 110 VSCT neurones, the VST evoked monosynaptic EPSPs in 27, di- or polysynaptic EPSPs in 56 and disynaptic IPSPs in 26. In 93 tested VSCT cells, MLF stimulation evoked monosynaptic EPSPs in 26, monosynaptic IPSPs in 2, di- or polysynaptic EPSPs in 25 and disynaptic IPSPs in 21. Convergence of monosynaptic EPSPs from VST and MLF was found in a small proportion of cells whereas the two descending pathways evoked reciprocal effects in another small group of neurones. Convergence of monosynaptic EPSPs from VST or MLF and from group I afferents was also modest. In 9 VSCT neurones there was convergence of monosynaptic excitation and disynaptic inhibition from the vestibulospinal tract and the same pattern from MLF was recorded in 9 neurones. The results are discussed in view of the hypothesis that VSCT neurones carry information on the interneuronal ttransmission in the spinal cord.", "contents": "Effects on the ventral spinocerebellar tract neurones from Deiters' nucleus and the medial longitudinal fascicle in the cat. Effects from the vestibulospinal tract (VST) and from fibres descending in the medial longitudinal fascicle (MLF) on the cells of origin of the ventral spinocerebellar tract (VSCT) have been studied with intracellular recording. Out of 110 VSCT neurones, the VST evoked monosynaptic EPSPs in 27, di- or polysynaptic EPSPs in 56 and disynaptic IPSPs in 26. In 93 tested VSCT cells, MLF stimulation evoked monosynaptic EPSPs in 26, monosynaptic IPSPs in 2, di- or polysynaptic EPSPs in 25 and disynaptic IPSPs in 21. Convergence of monosynaptic EPSPs from VST and MLF was found in a small proportion of cells whereas the two descending pathways evoked reciprocal effects in another small group of neurones. Convergence of monosynaptic EPSPs from VST or MLF and from group I afferents was also modest. In 9 VSCT neurones there was convergence of monosynaptic excitation and disynaptic inhibition from the vestibulospinal tract and the same pattern from MLF was recorded in 9 neurones. The results are discussed in view of the hypothesis that VSCT neurones carry information on the interneuronal ttransmission in the spinal cord."} {"id": "PMID:167550", "title": "Mitochondrial respiration in the ventricular myocardium and in the white and deep red myotomal muscles of juvenile tuna fish (thunnus thynnus L.).", "content": "The respiratory activity of mitochondria isolated from the outer and inner layers of the ventricular myocardium and from the white and deep red myotomal muscles of juvenile Thunnus thynnus has been compared. The highest values for the succinate oxidase and succinate cytochrome c reductase activities have been found in the mitochondria of the outer myocardial layer, followed by mitochondria of the deep red muscle, the inner myocardial layer and the white muscle in that order. Differences in mitochondrial NADH-cytochrome c reductase activity run parallel, in a lower order of magnitude, to the differences in the oxidation of succinate. This finding is discussed in relation to the different metabolic attitudes of the muscle tissues towards anaerobic glycolysis. The outer myocardial layer of the juvenile tuna ventricle has been shown to have a higher metabolic activity than the inner layer, in contrast to the situation in adult ventricular myocardium.", "contents": "Mitochondrial respiration in the ventricular myocardium and in the white and deep red myotomal muscles of juvenile tuna fish (thunnus thynnus L.). The respiratory activity of mitochondria isolated from the outer and inner layers of the ventricular myocardium and from the white and deep red myotomal muscles of juvenile Thunnus thynnus has been compared. The highest values for the succinate oxidase and succinate cytochrome c reductase activities have been found in the mitochondria of the outer myocardial layer, followed by mitochondria of the deep red muscle, the inner myocardial layer and the white muscle in that order. Differences in mitochondrial NADH-cytochrome c reductase activity run parallel, in a lower order of magnitude, to the differences in the oxidation of succinate. This finding is discussed in relation to the different metabolic attitudes of the muscle tissues towards anaerobic glycolysis. The outer myocardial layer of the juvenile tuna ventricle has been shown to have a higher metabolic activity than the inner layer, in contrast to the situation in adult ventricular myocardium."} {"id": "PMID:167551", "title": "The action of dibutyryl adenosine-3':5'-cyclic monophosphoric acid and theophylline on the isolated cat parotid gland.", "content": "In the isolated cat parotid gland intraarterially applied dibutyryl cyclic AMP (db-cAMP) (1.0 mM) produced a slow, but often maintained salivary flow. db-cAMP was also able to potentiate secretion evoked by supramaximal doses of intraarterially applied acetylcholine. Similar secretory effects were obtained also after intraarterial application of theophylline (1.0 mM). The secretory responses due to db-cAMP or theophylline were unaccompanied by measurable acinar membrane potential changes and stayed unchanged after cutting the parasympathetic innervation of the gland and after blocking both cholinergic and beta-adrenergic receptors with atropine (10-minus 7 M), and with D-(minus)-N-isopropyl-p-nitrophenol-ethanolamine (INPEA) (10-minus 5 M), respectively. The possibility of the existence of an acinar adenylate cyclase system functionally linked to the beta-adrenergic membrane receptor is discussed.", "contents": "The action of dibutyryl adenosine-3':5'-cyclic monophosphoric acid and theophylline on the isolated cat parotid gland. In the isolated cat parotid gland intraarterially applied dibutyryl cyclic AMP (db-cAMP) (1.0 mM) produced a slow, but often maintained salivary flow. db-cAMP was also able to potentiate secretion evoked by supramaximal doses of intraarterially applied acetylcholine. Similar secretory effects were obtained also after intraarterial application of theophylline (1.0 mM). The secretory responses due to db-cAMP or theophylline were unaccompanied by measurable acinar membrane potential changes and stayed unchanged after cutting the parasympathetic innervation of the gland and after blocking both cholinergic and beta-adrenergic receptors with atropine (10-minus 7 M), and with D-(minus)-N-isopropyl-p-nitrophenol-ethanolamine (INPEA) (10-minus 5 M), respectively. The possibility of the existence of an acinar adenylate cyclase system functionally linked to the beta-adrenergic membrane receptor is discussed."} {"id": "PMID:167553", "title": "Adult hypophosphatasia.", "content": "A case of adult hypophosphatasia under treatment with a high orthophosphate (P1) intake is described. The patient is a 53-year-old woman. Her symptoms have progressed for seven years, and it has been necessary to perform osteosynthesis of both crura. The diagnosis rests upon a characteristic clinical picture, low serum alkaline phosphatase activity, high urinary excretion of phosphoethanolamine, and an invariably elevated concentration of inorganic pyrophosphate (PP1) in plasma accompanied by a very high excretion of this compound in the urine. An improved technique allowed specific determinations of microquantities of PP1 in biologic materials. The concentrations of PP1 in the plasma and urine remained unchanged when the patient's intake of phosphorus was increased to 1.98 g/day. The PP1/P1 ratio in the urine was 10-20 before treatment. During treatment P1 excretion increased. PP1 excretion did not change, and the ratio decreased to around 7. The renal tubular transport of PP1 probably was saturated, and therefore PP1, which was circulating in abnormally high concentrations in the patient's fluids, could not be removed by loading with P1. Four months of treatment did not benefit the patient.", "contents": "Adult hypophosphatasia. A case of adult hypophosphatasia under treatment with a high orthophosphate (P1) intake is described. The patient is a 53-year-old woman. Her symptoms have progressed for seven years, and it has been necessary to perform osteosynthesis of both crura. The diagnosis rests upon a characteristic clinical picture, low serum alkaline phosphatase activity, high urinary excretion of phosphoethanolamine, and an invariably elevated concentration of inorganic pyrophosphate (PP1) in plasma accompanied by a very high excretion of this compound in the urine. An improved technique allowed specific determinations of microquantities of PP1 in biologic materials. The concentrations of PP1 in the plasma and urine remained unchanged when the patient's intake of phosphorus was increased to 1.98 g/day. The PP1/P1 ratio in the urine was 10-20 before treatment. During treatment P1 excretion increased. PP1 excretion did not change, and the ratio decreased to around 7. The renal tubular transport of PP1 probably was saturated, and therefore PP1, which was circulating in abnormally high concentrations in the patient's fluids, could not be removed by loading with P1. Four months of treatment did not benefit the patient."} {"id": "PMID:167554", "title": "Mammalian liver alcohol dehydrogenases.", "content": "Literature on the properties of liver alcohol dehydrogenase (ADH) from man, horse and rat is reviewed and discussed under two major headings: 1) physical and chemical properties of ADH and 2) structure-function relationship in isoenzymes. Under the first heading are discussed: molecular weight, subunit composition catalytic sites per molecule, sulfhydryl groups, end groups, amino acid composition, role of Zn++ in the structure and function, coenzyme specificity and binding, conformational changes, substrate specificity, catalytic mechanism and recent results from x-ray crystallography of horse liver ADH. The physicochemical properties of ADH from man, horse and rat are for the most part similar. All three enzymes have identical molecular weights, similar amino acid compositions, consist of two subunits, and are all metalloenzymes containing Zn++: horse and human ADH contain one coenzyme binding site per subunit; no results are available for the rat ADH. ADH catalyses interconversion of a large variety of saturated and unsaturated aliphatic and aromatic alcohols and the corresponding aldehydes and ketones utilizing NAD(H). The physiological role of ADH is uncertain. ADH readily combines with reduced coenzymes to form binary complexes with low dissociation constants (10-7 to 10-8M); in the ternary complexes with coenzymes and substrate-competitive inhibitors, these constants are even lower. In the presence of suitable inhibitors, the enzymes can be titrated by coenzymes employing fluorometric and spectrophotometric procedures. The rate of the overall reaction catalyzed by ADH is determined by the dissociation rates of coenzymes, the slowest steps in the reaction sequence. Under the second heading are discussed: liver ADH isoenzymes of horse, man, rat, rhesus monkey and other species, and the significance of steroid activity which accounts for the distinct substrate specificity of some isoenzymes. ADH from horse liver is a heterogeneous enzyme consisting of subunits of distinct substrate specificity and primary structure. The difference in the amino acid sequence between subunit E (active with classical ADH substrates, but not with steroids) and subunit S (active also with steroids) amounts to six amino acids out of 374. Human ADH is also heterogeneous, and at least five genes code for polypeptides which, by dimerization, form different isoenzymes. Experimental evidence suggests that rat ADH is a single unique protein which, like horse liver ADH, SS, is active with steroids. The physiological significance of steroid activity of ADHs is unknown. (Four tables with comparative data and one figure are presented).", "contents": "Mammalian liver alcohol dehydrogenases. Literature on the properties of liver alcohol dehydrogenase (ADH) from man, horse and rat is reviewed and discussed under two major headings: 1) physical and chemical properties of ADH and 2) structure-function relationship in isoenzymes. Under the first heading are discussed: molecular weight, subunit composition catalytic sites per molecule, sulfhydryl groups, end groups, amino acid composition, role of Zn++ in the structure and function, coenzyme specificity and binding, conformational changes, substrate specificity, catalytic mechanism and recent results from x-ray crystallography of horse liver ADH. The physicochemical properties of ADH from man, horse and rat are for the most part similar. All three enzymes have identical molecular weights, similar amino acid compositions, consist of two subunits, and are all metalloenzymes containing Zn++: horse and human ADH contain one coenzyme binding site per subunit; no results are available for the rat ADH. ADH catalyses interconversion of a large variety of saturated and unsaturated aliphatic and aromatic alcohols and the corresponding aldehydes and ketones utilizing NAD(H). The physiological role of ADH is uncertain. ADH readily combines with reduced coenzymes to form binary complexes with low dissociation constants (10-7 to 10-8M); in the ternary complexes with coenzymes and substrate-competitive inhibitors, these constants are even lower. In the presence of suitable inhibitors, the enzymes can be titrated by coenzymes employing fluorometric and spectrophotometric procedures. The rate of the overall reaction catalyzed by ADH is determined by the dissociation rates of coenzymes, the slowest steps in the reaction sequence. Under the second heading are discussed: liver ADH isoenzymes of horse, man, rat, rhesus monkey and other species, and the significance of steroid activity which accounts for the distinct substrate specificity of some isoenzymes. ADH from horse liver is a heterogeneous enzyme consisting of subunits of distinct substrate specificity and primary structure. The difference in the amino acid sequence between subunit E (active with classical ADH substrates, but not with steroids) and subunit S (active also with steroids) amounts to six amino acids out of 374. Human ADH is also heterogeneous, and at least five genes code for polypeptides which, by dimerization, form different isoenzymes. Experimental evidence suggests that rat ADH is a single unique protein which, like horse liver ADH, SS, is active with steroids. The physiological significance of steroid activity of ADHs is unknown. (Four tables with comparative data and one figure are presented)."} {"id": "PMID:167555", "title": "The effects of aliphatic alcohols on the biophysical and biochemical correlates of membrane function.", "content": "The simplicity of the structure of aliphatic alcohols suggests that their interaction with receptors in the classical sense is unlikely. The actions of alcohols may involve a relatively nonspecific disruption of cell membranes, possibly physically dissolving into neuronal membranes especially, resulting in the malfunction of normal physiological processes. Studies of alcohol-membrane interactions have employed the use of artificial and nonneural membranes, invertebrate neurons for electrophysiological measurements and brain tissue for studying ion fluxes and enzymatic activities. For the most part these studies have been inclusive because high concentrations of alcohols were needed to elicit any effect. Also, it is difficult to extrapolate the data to in vivo mammalian systems, especially relative to the clinical signs of depression of the central nervous system.", "contents": "The effects of aliphatic alcohols on the biophysical and biochemical correlates of membrane function. The simplicity of the structure of aliphatic alcohols suggests that their interaction with receptors in the classical sense is unlikely. The actions of alcohols may involve a relatively nonspecific disruption of cell membranes, possibly physically dissolving into neuronal membranes especially, resulting in the malfunction of normal physiological processes. Studies of alcohol-membrane interactions have employed the use of artificial and nonneural membranes, invertebrate neurons for electrophysiological measurements and brain tissue for studying ion fluxes and enzymatic activities. For the most part these studies have been inclusive because high concentrations of alcohols were needed to elicit any effect. Also, it is difficult to extrapolate the data to in vivo mammalian systems, especially relative to the clinical signs of depression of the central nervous system."} {"id": "PMID:167556", "title": "Interactions of ethanol with cyclic AMP.", "content": "Ethanol and other alcohols stimulate adenylate cyclase activity in various tissues and potentiate its stimulation by some hormones. This effect, however, usually requires a high alcohol concentration. In some cases, an unknown substance, different from cyclic AMP, was formed from ATP in the presence of an alcohol and mimicked stimulation of adenylate cyclase. Ethanol inhibits phosphodiesterase activity in some tissues. In the brain, only the low affinity enzyme of pons-medulla region is inhibited. ATP levels and ATPase activities are affected by ethanol treatment and this can lead to secondary changes of the cyclic AMP levels. Cyclic AMP levels in the brain and liver are decreased by acute ethanol administration while levels in other organs are unchanged. High doses of ethanol inhibit the postdecapitation-induced rise of cyclic AMP level in the brain while low ethanol doses potentiate the postdecapitation rise of cyclic AMP in the lower brain stem. Chronic ethanol administration increases basal adenylate cyclase activity and cyclic AMP levels, and decreases stimulation of adenylate cyclase by norepinephrine in the brain. In contrast, the stimulation of cyclic AMP formation by norepinephrine and other biogenic amines is increased in the brain of ethanol-withdrawn animals. Chronic administration of ethanol affects also cyclic AMP levels and cyclic AMP formation in some peripheral organs. Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation.", "contents": "Interactions of ethanol with cyclic AMP. Ethanol and other alcohols stimulate adenylate cyclase activity in various tissues and potentiate its stimulation by some hormones. This effect, however, usually requires a high alcohol concentration. In some cases, an unknown substance, different from cyclic AMP, was formed from ATP in the presence of an alcohol and mimicked stimulation of adenylate cyclase. Ethanol inhibits phosphodiesterase activity in some tissues. In the brain, only the low affinity enzyme of pons-medulla region is inhibited. ATP levels and ATPase activities are affected by ethanol treatment and this can lead to secondary changes of the cyclic AMP levels. Cyclic AMP levels in the brain and liver are decreased by acute ethanol administration while levels in other organs are unchanged. High doses of ethanol inhibit the postdecapitation-induced rise of cyclic AMP level in the brain while low ethanol doses potentiate the postdecapitation rise of cyclic AMP in the lower brain stem. Chronic ethanol administration increases basal adenylate cyclase activity and cyclic AMP levels, and decreases stimulation of adenylate cyclase by norepinephrine in the brain. In contrast, the stimulation of cyclic AMP formation by norepinephrine and other biogenic amines is increased in the brain of ethanol-withdrawn animals. Chronic administration of ethanol affects also cyclic AMP levels and cyclic AMP formation in some peripheral organs. Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation."} {"id": "PMID:167557", "title": "Rate-limiting steps in ethanol metabolism and approaches to changing these rates biochemically.", "content": "Ethanol is oxidized to acetate primarily by a system involving liver alcohol and aldehyde dehydrogenases coupled with reoxidation of NADH by the mitochondria. All of these steps are at least partially rate-limiting in ethanol metabolism, with alcohol dehydrogenase and oxidative phosphorylation probably slower than the others. More research is required to assess the quantitative roles of various steps. Many agents are ineffective in changing the rate of metabolism of ethanol, but fructose and dinitrophenol may increase the rate by up to 1.5-fold in vivo. The failure of single agents to increase the rate substantially may indicate that when one step is accelerated, another step becomes rate-limited. Therefore, combinations of agents that affect several steps simultaneously may be required for acceleration. Effective experimental methods for inhibiting alcohol dehydrogenase in vivo are available.", "contents": "Rate-limiting steps in ethanol metabolism and approaches to changing these rates biochemically. Ethanol is oxidized to acetate primarily by a system involving liver alcohol and aldehyde dehydrogenases coupled with reoxidation of NADH by the mitochondria. All of these steps are at least partially rate-limiting in ethanol metabolism, with alcohol dehydrogenase and oxidative phosphorylation probably slower than the others. More research is required to assess the quantitative roles of various steps. Many agents are ineffective in changing the rate of metabolism of ethanol, but fructose and dinitrophenol may increase the rate by up to 1.5-fold in vivo. The failure of single agents to increase the rate substantially may indicate that when one step is accelerated, another step becomes rate-limited. Therefore, combinations of agents that affect several steps simultaneously may be required for acceleration. Effective experimental methods for inhibiting alcohol dehydrogenase in vivo are available."} {"id": "PMID:167559", "title": "The effects of feeding various carbohydrates on the development of hypercholesterolemia and atherosclerosis.", "content": "It is possible to establish atherosclerosis in rabbits by feeding semi-synthetic diets that are high in carbohydrate and saturated fat and devoid of cholesterol. Addition of saturated fat to laboratory chow does not render the chow atherogenic. When rabbits were fed diets which differ only in the carbohydrate component, starch was found to be more atherogenic than sucrose which, in turn, was more atherogenic than glucose. All the diets were hypercholesteremic and hypertriglyceridemic. In another series of experiments diets containing fructose or sucrose were more atherogenic than diets containing glucose, lactose or sorbitol. Baboons were feed semi-synthetic diets containing fructose, sucrose, starch or glucose (but no cholesterol) for one year. Serum cholesterol levels were 155-165 mg/dl in all test groups. The normal baboon cholesterol level is 115 mg/dl. Serum triglycerides were elevated from the normal level of 73 mg/dl to about 110 mg/dl in the groups fed starch and glucose and to about 125 mg/dl in the groups fed fructose and sucrose. Liver and lung cholesterol ester levels were also raised. The test groups all showed aortic sudanophilia. The most severe sudanophilia was observed in the fructose group (11.2% of surface area) and the least in the glucose group (6.2% of surface area). The biliary cholesterol specific activities (after administration of (3-H)-melvalonic acid) were the same in all groups, but biliary bile acid specific activity was higher in the control baboons than in test animals. These data, plus the higher primary/secondary bile acid ratio observed in the test animals, suggest that reduced bile acid synthesis may be one cause of the hypercholesteremia observed in animals fed the semi-synthetic diets.", "contents": "The effects of feeding various carbohydrates on the development of hypercholesterolemia and atherosclerosis. It is possible to establish atherosclerosis in rabbits by feeding semi-synthetic diets that are high in carbohydrate and saturated fat and devoid of cholesterol. Addition of saturated fat to laboratory chow does not render the chow atherogenic. When rabbits were fed diets which differ only in the carbohydrate component, starch was found to be more atherogenic than sucrose which, in turn, was more atherogenic than glucose. All the diets were hypercholesteremic and hypertriglyceridemic. In another series of experiments diets containing fructose or sucrose were more atherogenic than diets containing glucose, lactose or sorbitol. Baboons were feed semi-synthetic diets containing fructose, sucrose, starch or glucose (but no cholesterol) for one year. Serum cholesterol levels were 155-165 mg/dl in all test groups. The normal baboon cholesterol level is 115 mg/dl. Serum triglycerides were elevated from the normal level of 73 mg/dl to about 110 mg/dl in the groups fed starch and glucose and to about 125 mg/dl in the groups fed fructose and sucrose. Liver and lung cholesterol ester levels were also raised. The test groups all showed aortic sudanophilia. The most severe sudanophilia was observed in the fructose group (11.2% of surface area) and the least in the glucose group (6.2% of surface area). The biliary cholesterol specific activities (after administration of (3-H)-melvalonic acid) were the same in all groups, but biliary bile acid specific activity was higher in the control baboons than in test animals. These data, plus the higher primary/secondary bile acid ratio observed in the test animals, suggest that reduced bile acid synthesis may be one cause of the hypercholesteremia observed in animals fed the semi-synthetic diets."} {"id": "PMID:167566", "title": "Piribedil and apomorphine: pre- and postsynaptic effects on dopamine synthesis and neuronal activity.", "content": "Piribedil and apomorphine can cause a complete but temporary inhibition in firing of the DA-containing neurons. The cells recover to approximately 30 to 40% of the original firing rate, and with subsequent administration of the drug become more and more resistant to further inhibition. At this point they are also resistant to inhibition by other direct- or indirect-acting DA agonists that are normally able to inhibit the firing of DA cells. This effect may be due to an interaction of the DA agonists with the postsynaptic DA receptors, but apomorphine at least is able to inhibit the firing of DA cells directly when iontophoresed onto the DA cell body (Aghajanian and Bunney, 1973). These drugs can block the increase in DA synthesis observed in the absence of impulse flow, indicating a presynaptic site of acttion. Taken together, these results suggest that in interpreting the effects of drugs interacting with the DA systems several points of interaction should be considered.", "contents": "Piribedil and apomorphine: pre- and postsynaptic effects on dopamine synthesis and neuronal activity. Piribedil and apomorphine can cause a complete but temporary inhibition in firing of the DA-containing neurons. The cells recover to approximately 30 to 40% of the original firing rate, and with subsequent administration of the drug become more and more resistant to further inhibition. At this point they are also resistant to inhibition by other direct- or indirect-acting DA agonists that are normally able to inhibit the firing of DA cells. This effect may be due to an interaction of the DA agonists with the postsynaptic DA receptors, but apomorphine at least is able to inhibit the firing of DA cells directly when iontophoresed onto the DA cell body (Aghajanian and Bunney, 1973). These drugs can block the increase in DA synthesis observed in the absence of impulse flow, indicating a presynaptic site of acttion. Taken together, these results suggest that in interpreting the effects of drugs interacting with the DA systems several points of interaction should be considered."} {"id": "PMID:167570", "title": "The efficiency of protective hoods used by sandblasters to reduce silica dust exposure.", "content": "Several types of respiratory protective hoods used by sandblasters were investigated in two steel fabrication yards. MSA Gravimetric Dust Samplers were used to collect respirable dust samples outside and inside hoods during sandblasting. Colorimetric and x-ray diffraction techniques were applied to the samples for free-silica determination. The majority of the sandblasters, who wore various types of air-supplied hoods, were exposed to an average level of silica dust several times higher than the TLV. Sandblasters wearing non-air-supplied hoods were at the greatest risk. Modern well maintained and properly worn air-supplied hoods offered fair protection during sandblasting periods, but the concentration of suspended respirable dust in ambient air during non-blasting intervals exceeded the TLV by several times.", "contents": "The efficiency of protective hoods used by sandblasters to reduce silica dust exposure. Several types of respiratory protective hoods used by sandblasters were investigated in two steel fabrication yards. MSA Gravimetric Dust Samplers were used to collect respirable dust samples outside and inside hoods during sandblasting. Colorimetric and x-ray diffraction techniques were applied to the samples for free-silica determination. The majority of the sandblasters, who wore various types of air-supplied hoods, were exposed to an average level of silica dust several times higher than the TLV. Sandblasters wearing non-air-supplied hoods were at the greatest risk. Modern well maintained and properly worn air-supplied hoods offered fair protection during sandblasting periods, but the concentration of suspended respirable dust in ambient air during non-blasting intervals exceeded the TLV by several times."} {"id": "PMID:167571", "title": "A retrospective study of clinical, physiologic and immunologic changes in workers exposed to toluene diisocyanate.", "content": "A retrospective study was made of workers in a toluene disocyanate plant using an immunologic test procedure developed at the NIOSH laboratories. Case histories of 32 workers in seven response groupings are presented. Sensitization was found to correlate with the frequency and severity of significant exposures to TDI. Immunologic changes producing tolerance to TDI exposure also resulted in negative response to the antigen challenge tests. Some individuals exposed to TDI may have protective antibodies but still experience bronchoconstriction.", "contents": "A retrospective study of clinical, physiologic and immunologic changes in workers exposed to toluene diisocyanate. A retrospective study was made of workers in a toluene disocyanate plant using an immunologic test procedure developed at the NIOSH laboratories. Case histories of 32 workers in seven response groupings are presented. Sensitization was found to correlate with the frequency and severity of significant exposures to TDI. Immunologic changes producing tolerance to TDI exposure also resulted in negative response to the antigen challenge tests. Some individuals exposed to TDI may have protective antibodies but still experience bronchoconstriction."} {"id": "PMID:167572", "title": "A technique for dynamic calibration of a continuous toluene diisocyanate monitor.", "content": "A method was developed for generation of atmospheric concentrations of toluene dissocyanate at 0.005 to 0.08 parts per million. This paper describes an analytical methods for the calibration of a continuous 701 Monitor using a diffusion cell to generate constant concentrations of TDI.", "contents": "A technique for dynamic calibration of a continuous toluene diisocyanate monitor. A method was developed for generation of atmospheric concentrations of toluene dissocyanate at 0.005 to 0.08 parts per million. This paper describes an analytical methods for the calibration of a continuous 701 Monitor using a diffusion cell to generate constant concentrations of TDI."} {"id": "PMID:167573", "title": "Policy and procedural guidelines for the health and safety of workers in virus laboratories.", "content": "Through the use of a (a) a questionnaire, designed to elicit background information, (b) a serological survey, designed to obtain a picture of virus dissemination, and (c) a library review, designed to gain insight into the area of virus laboratory problems, the state of hazard in animal virus laboratories at Yale was evaluated. On the basis of this evaluation, a series of recommended guidelines for protecting the health and safety of workers in those laboratories was formulated.", "contents": "Policy and procedural guidelines for the health and safety of workers in virus laboratories. Through the use of a (a) a questionnaire, designed to elicit background information, (b) a serological survey, designed to obtain a picture of virus dissemination, and (c) a library review, designed to gain insight into the area of virus laboratory problems, the state of hazard in animal virus laboratories at Yale was evaluated. On the basis of this evaluation, a series of recommended guidelines for protecting the health and safety of workers in those laboratories was formulated."} {"id": "PMID:167574", "title": "The genesis of cell types in the adenohypophysis of the human fetus as observed with immunocytochemistry.", "content": "Hypophyses of 21 human fetuses, ranging in gestational age from 6 to 23 weeks, were studied by immunocytochemical and histological staining to ascertain (1) the time of origin of specific cell types and (2) the development of parenchymal cell zonation in the pars distalis. No hormones were identified at six weeks. Probable corticotrophin-containing cells appeared at seven weeks. Somatotrophs were observed first at 10.5 weeks; correlation with other reports indicates that they appear at eight to nine weeks. Melanotrophs were detected at 14 weeks; the cells containing melanotrophin were far fewer than corticotrophs. The youngest fetus to possess gonadotrophs was 10.5 weeks old. In all specimens gonadotrophs (LH-cells) stained well with immunocytochemical procedures but poorly with histological methods. Thyrotrophs first occurred at 13 weeks. Zonal distribution of cell types in the pars distalis was evident almost from the time of their appearance. Somatotrophs were most numerous laterally and immediately anterior to the residual cleft. At 10.5 weeks corticotrophs were confined chiefly to the borders of vascularized connective tissue (trabeculae) and to the lateral peripheral region of the pars distalis. Thyrotrophs appeared chiefly in the anteromedian zone, particularly in its superior portion, but were found laterally also. In the older specimens, gonadotrophs generally occurred throughout the pars distalis but were less numerous near the trabeculae and in the anterolateral region. There was good correlation between the time of appearance of various cell types and published data on secretory capacity of the gland.", "contents": "The genesis of cell types in the adenohypophysis of the human fetus as observed with immunocytochemistry. Hypophyses of 21 human fetuses, ranging in gestational age from 6 to 23 weeks, were studied by immunocytochemical and histological staining to ascertain (1) the time of origin of specific cell types and (2) the development of parenchymal cell zonation in the pars distalis. No hormones were identified at six weeks. Probable corticotrophin-containing cells appeared at seven weeks. Somatotrophs were observed first at 10.5 weeks; correlation with other reports indicates that they appear at eight to nine weeks. Melanotrophs were detected at 14 weeks; the cells containing melanotrophin were far fewer than corticotrophs. The youngest fetus to possess gonadotrophs was 10.5 weeks old. In all specimens gonadotrophs (LH-cells) stained well with immunocytochemical procedures but poorly with histological methods. Thyrotrophs first occurred at 13 weeks. Zonal distribution of cell types in the pars distalis was evident almost from the time of their appearance. Somatotrophs were most numerous laterally and immediately anterior to the residual cleft. At 10.5 weeks corticotrophs were confined chiefly to the borders of vascularized connective tissue (trabeculae) and to the lateral peripheral region of the pars distalis. Thyrotrophs appeared chiefly in the anteromedian zone, particularly in its superior portion, but were found laterally also. In the older specimens, gonadotrophs generally occurred throughout the pars distalis but were less numerous near the trabeculae and in the anterolateral region. There was good correlation between the time of appearance of various cell types and published data on secretory capacity of the gland."} {"id": "PMID:167575", "title": "Morphological effects of a large single dose of cycloheximide on the intestinal epithelium of the rat.", "content": "Adult male rats received 15 mg/kg cycloheximide and the subsequent morphological effects at three and six hours after injection were evaluated using histometry, light and electron microscopy, histological demonstration of terminal web and acid phosphatase, and radioautography with tritiated thymidine. Rapid atrophy of the villi took place, progressing from the villus tip by premature exfoliation of epithelial cells. The crypts also diminished by random exfoliation of many crypt cells and by partial or complete disintegration. Mitosis and epithelial cell migration were absent. By six hours, the area occupied by the villi and the crypts per unit length of histological section was decreased by about 70-90% in most of the small intestine but only by about 40-60% in the duodenum and the terminal ileum. In the upper half of the villi, the epithelium was strongly positive for acid phosphatase and contained large numbers of round bodies resembling primary lysosomes. In the lower half, the microvillous border and terminal web were found to be disrupted. Animals receiving only 5 mg/kg cycloheximide also showed the atrophy of villi and crypts, and the round bodies resembling lysosomes. Evidence from several sources has indicated that protein synthesis in normal villus epithelial cells subsides toward the villus tip and becomes minimal at exfoliation. At exfoliation, proteins responsible for epithelial cohesion probably fail because they are no longer replenished. Cycloheximide appears to accelerate this process.", "contents": "Morphological effects of a large single dose of cycloheximide on the intestinal epithelium of the rat. Adult male rats received 15 mg/kg cycloheximide and the subsequent morphological effects at three and six hours after injection were evaluated using histometry, light and electron microscopy, histological demonstration of terminal web and acid phosphatase, and radioautography with tritiated thymidine. Rapid atrophy of the villi took place, progressing from the villus tip by premature exfoliation of epithelial cells. The crypts also diminished by random exfoliation of many crypt cells and by partial or complete disintegration. Mitosis and epithelial cell migration were absent. By six hours, the area occupied by the villi and the crypts per unit length of histological section was decreased by about 70-90% in most of the small intestine but only by about 40-60% in the duodenum and the terminal ileum. In the upper half of the villi, the epithelium was strongly positive for acid phosphatase and contained large numbers of round bodies resembling primary lysosomes. In the lower half, the microvillous border and terminal web were found to be disrupted. Animals receiving only 5 mg/kg cycloheximide also showed the atrophy of villi and crypts, and the round bodies resembling lysosomes. Evidence from several sources has indicated that protein synthesis in normal villus epithelial cells subsides toward the villus tip and becomes minimal at exfoliation. At exfoliation, proteins responsible for epithelial cohesion probably fail because they are no longer replenished. Cycloheximide appears to accelerate this process."} {"id": "PMID:167576", "title": "Cytomegalovirus studies of autopsy tissue. I. Virus isolation.", "content": "From January through September 1973, 55 virus isolates were recovered from lung and kidney specimens from 44 (8.8%) of 502 unselected autopsy cases. Cytomegalovirus (CMV) was isolated 42 times in 34 cases (36 from lung, four from kidney, and one each from pleural and bronchial tissues). Virus isolation was approximately six times more sensitive than histologic detection of CMV infections. Major causes of death included solid malignant tumors, leukemia, lymphoma, and renal allograft rejection; 13 patients had a variety of other diseases, predominantly cardiopulmonary. CMV was recovered from more males than females. The mean age of the CMV-positive group did not differ significantly from that of the CMV-negative group. CMV-positive cases were not preselected on the basis of specimen processing time. Serologic results indicate that recovery of CMV from an autopsy case was seven times more likely when the complement-fixing antibody titer was 1:16 or more.", "contents": "Cytomegalovirus studies of autopsy tissue. I. Virus isolation. From January through September 1973, 55 virus isolates were recovered from lung and kidney specimens from 44 (8.8%) of 502 unselected autopsy cases. Cytomegalovirus (CMV) was isolated 42 times in 34 cases (36 from lung, four from kidney, and one each from pleural and bronchial tissues). Virus isolation was approximately six times more sensitive than histologic detection of CMV infections. Major causes of death included solid malignant tumors, leukemia, lymphoma, and renal allograft rejection; 13 patients had a variety of other diseases, predominantly cardiopulmonary. CMV was recovered from more males than females. The mean age of the CMV-positive group did not differ significantly from that of the CMV-negative group. CMV-positive cases were not preselected on the basis of specimen processing time. Serologic results indicate that recovery of CMV from an autopsy case was seven times more likely when the complement-fixing antibody titer was 1:16 or more."} {"id": "PMID:167577", "title": "Cytomegalovirus studies of autopsy tissue. II. Incidence of inclusion bodies and related pathologic data.", "content": "Cytomegaloviruses (CMV) were recovered from lung tissue in 34 (6.8%) of 502 unselected autopsy cases. Inclusion bodies were detected in the lung in nine of these cases (26%) and in organs other than the lung in three others. Overall, the incidence of inclusion bodies in this series of 502 cases was 2.4%. Our data strongly indicate that virus isolation is more sensitive than histopathologic study in establishing the presence of CMV infection. However, CMV was not recovered from one kidney and one liver in which inclusion bodies were present, although the virus was isolated from lung. Four of five cases of renal allograft rejection were positive for both CMV and inclusion bodies. The incidence of CMV recovery and inclusion body detection in leukemia and lymphoma cases was more than twice that in cases with other diseases. CMV inclusion bodies with or without associated inflammation were found, in descending order of frequency, in the lung, kidney, liver, pancreas, adrenal gland, esophagus, prostate, testes, thyroid gland, parathyroid gland, stomach, small intestine, large intestine, and heart.", "contents": "Cytomegalovirus studies of autopsy tissue. II. Incidence of inclusion bodies and related pathologic data. Cytomegaloviruses (CMV) were recovered from lung tissue in 34 (6.8%) of 502 unselected autopsy cases. Inclusion bodies were detected in the lung in nine of these cases (26%) and in organs other than the lung in three others. Overall, the incidence of inclusion bodies in this series of 502 cases was 2.4%. Our data strongly indicate that virus isolation is more sensitive than histopathologic study in establishing the presence of CMV infection. However, CMV was not recovered from one kidney and one liver in which inclusion bodies were present, although the virus was isolated from lung. Four of five cases of renal allograft rejection were positive for both CMV and inclusion bodies. The incidence of CMV recovery and inclusion body detection in leukemia and lymphoma cases was more than twice that in cases with other diseases. CMV inclusion bodies with or without associated inflammation were found, in descending order of frequency, in the lung, kidney, liver, pancreas, adrenal gland, esophagus, prostate, testes, thyroid gland, parathyroid gland, stomach, small intestine, large intestine, and heart."} {"id": "PMID:167579", "title": "Ultrastructure of the skeletal muscles in acromegaly--before and after hypophysectomy.", "content": "Electron microscopic examination of the skeletal muscles in a patient with acromegaly and marked elevation of the serum growth hormone reveals altered mitochondria (pleomorphism, elongation, matrical pallor, and cristae abnormalities), glycogen granules infiltration, inclusion bodies, and vesicular dilatations. Nine months after surgical removal of the pituitary tumor, the serum growth hormone levels were markedly diminished. A repeat examination of the skeletal muscle shows that the previous ultrastructural changes in the muscles are related to the growth hormone levels.", "contents": "Ultrastructure of the skeletal muscles in acromegaly--before and after hypophysectomy. Electron microscopic examination of the skeletal muscles in a patient with acromegaly and marked elevation of the serum growth hormone reveals altered mitochondria (pleomorphism, elongation, matrical pallor, and cristae abnormalities), glycogen granules infiltration, inclusion bodies, and vesicular dilatations. Nine months after surgical removal of the pituitary tumor, the serum growth hormone levels were markedly diminished. A repeat examination of the skeletal muscle shows that the previous ultrastructural changes in the muscles are related to the growth hormone levels."} {"id": "PMID:167582", "title": "Anaerobic infections of the female genital tract.", "content": "Anaerobic bacterial organisms are a frequent cause of female genital tract infections. There has been a lack of appreciation of the significant role anaerobes play in obstetric and gynecologic infections. Utilization of newer appropriate anaerobic culture techniques has shown the importance of these organisms as pathogens in serious infections of the genital tract. Many species of anaerobic bacteria appear to be part of the normal microflora of the lower genital tract in female subjects. Similar organisms are frequently isolated from pelvic infections. Bacteroides, anaerobic cocci, and Clostridia are the most commonly isolated anaerobes associated with clinical infections. The clinician must recognize the presence of anaerobic infections, utilize proper anaerobic culture methods, and institute appropriate antibiotic and/or surgical therapy.", "contents": "Anaerobic infections of the female genital tract. Anaerobic bacterial organisms are a frequent cause of female genital tract infections. There has been a lack of appreciation of the significant role anaerobes play in obstetric and gynecologic infections. Utilization of newer appropriate anaerobic culture techniques has shown the importance of these organisms as pathogens in serious infections of the genital tract. Many species of anaerobic bacteria appear to be part of the normal microflora of the lower genital tract in female subjects. Similar organisms are frequently isolated from pelvic infections. Bacteroides, anaerobic cocci, and Clostridia are the most commonly isolated anaerobes associated with clinical infections. The clinician must recognize the presence of anaerobic infections, utilize proper anaerobic culture methods, and institute appropriate antibiotic and/or surgical therapy."} {"id": "PMID:167583", "title": "Comparison of antibiotic therapy in presumptive bacterial conjunctivitis.", "content": "One hundred twenty patients who met criteria for presumptive bacterial infections of the conjunctiva were closely recorded for two weeks in a double-blind study that compared the effectiveness of gentamicin with a combination of neomycin and polymyxin B sulfates. The neomycin and polymyxin B combination demonstrated statistical superiority as measured by patient improvement and failure to respond to therapy. However, difficulties including chance distribution of bacteria and variability of organism resistance may have detracted from statistical results.", "contents": "Comparison of antibiotic therapy in presumptive bacterial conjunctivitis. One hundred twenty patients who met criteria for presumptive bacterial infections of the conjunctiva were closely recorded for two weeks in a double-blind study that compared the effectiveness of gentamicin with a combination of neomycin and polymyxin B sulfates. The neomycin and polymyxin B combination demonstrated statistical superiority as measured by patient improvement and failure to respond to therapy. However, difficulties including chance distribution of bacteria and variability of organism resistance may have detracted from statistical results."} {"id": "PMID:167585", "title": "Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium.", "content": "The effect of ischemia on the integrity of myocardial lysosomes was observed 3 1/2 and 24 hours after the production of infarcts in 20 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. Biopsies from normal, marginal and infarcted areas were fixed and incubated to localize the lysosomal enzymes acid phosphatase and aryl sulphatase. Reaction product in normal cells was localized in small circular or oblong profiles between bundles of myofilaments and adjacent to mitochondria. In addition, curvilinear, membrane-bound profiles containing reaction product were found in close apposition to transverse tubules and near the free margins of the myocardial cells. Thus the distribution of elements of the sarcoplasmic reticulum. Additional reaction product was also seen in residual bodies, on myelin figures, and in the few conventional appearing spherical lysosomes. Little or no acid phosphatase or aryl sulphatase reaction product was seen in the sarcoplasmic reticulum of infarcted myocardium. The degree of cellular degeneration correlated with disappearance of enzyme activity from the sarcoplasmic reticulum and included disruption of membranes and loss of mitochondrial matrix and erosion of I but not A bands. Marginal areas showed variable amounts of cellular degeneration. Separation of myofilament bundles and loss of glycogen correlated with the localized disappearance of acid phosphatase and aryl sulphatase activity in marginal tissue. Disruption of mitochondrial and erosion of I bands correlated with extensive loss of these enzymes. The data suggest that degeneration of myocardial cells following ischemic injury is associated with release of endogenous lysosomal enzymes from the sarcoplasmic reticulum.", "contents": "Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium. The effect of ischemia on the integrity of myocardial lysosomes was observed 3 1/2 and 24 hours after the production of infarcts in 20 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. Biopsies from normal, marginal and infarcted areas were fixed and incubated to localize the lysosomal enzymes acid phosphatase and aryl sulphatase. Reaction product in normal cells was localized in small circular or oblong profiles between bundles of myofilaments and adjacent to mitochondria. In addition, curvilinear, membrane-bound profiles containing reaction product were found in close apposition to transverse tubules and near the free margins of the myocardial cells. Thus the distribution of elements of the sarcoplasmic reticulum. Additional reaction product was also seen in residual bodies, on myelin figures, and in the few conventional appearing spherical lysosomes. Little or no acid phosphatase or aryl sulphatase reaction product was seen in the sarcoplasmic reticulum of infarcted myocardium. The degree of cellular degeneration correlated with disappearance of enzyme activity from the sarcoplasmic reticulum and included disruption of membranes and loss of mitochondrial matrix and erosion of I but not A bands. Marginal areas showed variable amounts of cellular degeneration. Separation of myofilament bundles and loss of glycogen correlated with the localized disappearance of acid phosphatase and aryl sulphatase activity in marginal tissue. Disruption of mitochondrial and erosion of I bands correlated with extensive loss of these enzymes. The data suggest that degeneration of myocardial cells following ischemic injury is associated with release of endogenous lysosomal enzymes from the sarcoplasmic reticulum."} {"id": "PMID:167586", "title": "Mixed endocrine pancreatic tumors producing several peptide hormones.", "content": "Twenty-four endocrine pancreatic tumors were examined immunohistochemically for insulin, glucagon, gastrin and ACTH. In seven of these tumors, more than one peptide-hormone-containing cell type was observed. These seven tumors were also examined with conventional staining methods for the presence of A1, A2, and B cells. The results showed that these staining methods do not always distinguish between the different hormone-producing cell types of endocrine pancreatic tumors. In spite of the fact that several types of hormone-secreting cells were found in the tumors, the case histories described symptoms characteristic of hypersecretion of only one of the hormones. The hormone of the predominating cell type could not always explain the clinical symptoms. Our results indicate the endocrine pancreatic tumors often are multihormonal. Therefore, it would seem advisable to screen serum from all insuloma patients for a variety of peptide hormones.", "contents": "Mixed endocrine pancreatic tumors producing several peptide hormones. Twenty-four endocrine pancreatic tumors were examined immunohistochemically for insulin, glucagon, gastrin and ACTH. In seven of these tumors, more than one peptide-hormone-containing cell type was observed. These seven tumors were also examined with conventional staining methods for the presence of A1, A2, and B cells. The results showed that these staining methods do not always distinguish between the different hormone-producing cell types of endocrine pancreatic tumors. In spite of the fact that several types of hormone-secreting cells were found in the tumors, the case histories described symptoms characteristic of hypersecretion of only one of the hormones. The hormone of the predominating cell type could not always explain the clinical symptoms. Our results indicate the endocrine pancreatic tumors often are multihormonal. Therefore, it would seem advisable to screen serum from all insuloma patients for a variety of peptide hormones."} {"id": "PMID:167587", "title": "Experimental parainfluenza-type-1-virus-induced encephalopathy in the adult mouse. An ultrastructural study of early lesions.", "content": "The adult mouse inoculated intracerebrally with 6/94 strain of parainfluenza type 1 virus developed selective degenerative lesions in cerebral white matter. Ultrastrucrally, the infiltration of mononuclear cells, mostly lymphoid cells, apparently preceded the alterations of white matter parenchyma. The prominent feature of the white matter lesion was a lytic degeneration of both axon and myelin that seemed to be triggered by the mononuclear cell infiltration. Nucleocapsids of paramyxovirus were found only in ependymal cells and the very early stages of the infection. It is suggested that the mechanism of the white matter degeneration might be that of a virus-induced cell-mediated immune response directed at both the axon and myelin.", "contents": "Experimental parainfluenza-type-1-virus-induced encephalopathy in the adult mouse. An ultrastructural study of early lesions. The adult mouse inoculated intracerebrally with 6/94 strain of parainfluenza type 1 virus developed selective degenerative lesions in cerebral white matter. Ultrastrucrally, the infiltration of mononuclear cells, mostly lymphoid cells, apparently preceded the alterations of white matter parenchyma. The prominent feature of the white matter lesion was a lytic degeneration of both axon and myelin that seemed to be triggered by the mononuclear cell infiltration. Nucleocapsids of paramyxovirus were found only in ependymal cells and the very early stages of the infection. It is suggested that the mechanism of the white matter degeneration might be that of a virus-induced cell-mediated immune response directed at both the axon and myelin."} {"id": "PMID:167588", "title": "Phylogenetic significance of the skin of New World monkeys (order primates, infraorder Platyrrhini).", "content": "The combined properties of a given cutaneous system, like other characters classically employed by systematic zoologists, are useful criteria in the assessment of primate taxonomy and phylogeny. From the synthesis of all available data, it is also concluded that (1) the results define a baseline regarding the normal histology and histochemistry of the skin of most genera and many species of New World monkeys; (2) intrageneric and intraspecific subtleties in cutaneous variation exist in primate integument; (3) single and multiple cutaneous traits contribute to the characterization and accurate identification of most levels of taxa within the primate hierarchy; (4) some traits, however, negate recent taxonomic practices, e.g., the familial position of Callimico; (5) basic cutaneous patterns confirm currently accepted concepts of taxonomy and phylogeny; and (6) the various cutaneous signatures of extant platyrrhines record a history of adaptive radiation in isolation, and suggest that the designation of at least two distinct families is warranted.", "contents": "Phylogenetic significance of the skin of New World monkeys (order primates, infraorder Platyrrhini). The combined properties of a given cutaneous system, like other characters classically employed by systematic zoologists, are useful criteria in the assessment of primate taxonomy and phylogeny. From the synthesis of all available data, it is also concluded that (1) the results define a baseline regarding the normal histology and histochemistry of the skin of most genera and many species of New World monkeys; (2) intrageneric and intraspecific subtleties in cutaneous variation exist in primate integument; (3) single and multiple cutaneous traits contribute to the characterization and accurate identification of most levels of taxa within the primate hierarchy; (4) some traits, however, negate recent taxonomic practices, e.g., the familial position of Callimico; (5) basic cutaneous patterns confirm currently accepted concepts of taxonomy and phylogeny; and (6) the various cutaneous signatures of extant platyrrhines record a history of adaptive radiation in isolation, and suggest that the designation of at least two distinct families is warranted."} {"id": "PMID:167589", "title": "Age changes in the pubic symphysis of Macaca mulatta.", "content": "Age changes in the pubic symphyses of 142 Cayo Santiago rhesus monkeys (known age, sex and maternal genealogy) are described. Symphyseal development is sexually dimorphic. Males generate a ridge and furrow system which is gradually replaced by a solid ankylosis at the mid-sagittal plane. Female development parallels that of the male until puberty. With pregnancy and delivery, relaxation and reaggregation of pelvic ligaments binding the symphysis destroy the symphyseal face. Continued bearing of offspring inhibits mid-sagittal ankylosis. Limited estimates of skeletal age can be made by using symphyseal development as an indicator of senescence.", "contents": "Age changes in the pubic symphysis of Macaca mulatta. Age changes in the pubic symphyses of 142 Cayo Santiago rhesus monkeys (known age, sex and maternal genealogy) are described. Symphyseal development is sexually dimorphic. Males generate a ridge and furrow system which is gradually replaced by a solid ankylosis at the mid-sagittal plane. Female development parallels that of the male until puberty. With pregnancy and delivery, relaxation and reaggregation of pelvic ligaments binding the symphysis destroy the symphyseal face. Continued bearing of offspring inhibits mid-sagittal ankylosis. Limited estimates of skeletal age can be made by using symphyseal development as an indicator of senescence."} {"id": "PMID:167584", "title": "Resocialization of schizophrenic patients.", "content": "An increasing number of chronic schizophrenic veterans is being discharged through various community placement programs. Because of years of separation from the social changes that have occurred in the society they once knew, these veterans need to be reoriented to community living. This study describes the responses of four chronic schizophrenic veterans who participated in a program of intensive reorientation. After exposure to this program, the veterans' ability to show empathy for one another was more eventful than their accomplishment of specific skills. Follow-up evaluations indicated that the veterans had gained social interest and competence and demonstrated less pathology.", "contents": "Resocialization of schizophrenic patients. An increasing number of chronic schizophrenic veterans is being discharged through various community placement programs. Because of years of separation from the social changes that have occurred in the society they once knew, these veterans need to be reoriented to community living. This study describes the responses of four chronic schizophrenic veterans who participated in a program of intensive reorientation. After exposure to this program, the veterans' ability to show empathy for one another was more eventful than their accomplishment of specific skills. Follow-up evaluations indicated that the veterans had gained social interest and competence and demonstrated less pathology."} {"id": "PMID:167590", "title": "Impaired renal response to parathyroid hormone in potassium depletion.", "content": "In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation was due to inhibition of adenylate cyclase. 4) The phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation.", "contents": "Impaired renal response to parathyroid hormone in potassium depletion. In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation was due to inhibition of adenylate cyclase. 4) The phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation."} {"id": "PMID:167591", "title": "Uptake of adenosine by dispersed chich embryonic cardiac cells.", "content": "Adenosine is involved in the regulation of coronary blood flow, but its mechanism of action is not clear. The present investigation is an attempt to understand the mechanism(s) of uptake of adenosine in dispersed chick embryonic cardiac cells and its relationship to the adenosine hypothesis. Adenosine is readily taken up by these cardiac cells, and a small fraction is incorporated into adenine nucleotides, whereas a major fraction is deaminated to inosine. The mechanism of uptake is different in 12- to 15-day-old chick embryos compared to 16- to 22-day-old embryos. The younger embryo heart cells show the incorporation of adenosine into adenine mononucleotides of the incubation medium as well as all the adenine nucleotides of the cells, whereas the older embryo heart cells show incorporation of adenosine only into the adenine nucleotides of the cells. The isolated cells used in the present study do not leak any significant amounts of adenosine kinase and/or nucleotides, and free adenosine was not found in the cells, even with extracellular concentrations as high as 1 mM. The absence of free adenosine in isolated dispersed cells reflects the activities of adenosine kinase and adenosine deaminase and is compatible with the adenosine hypothesis for the regulation of coronary blood flow.", "contents": "Uptake of adenosine by dispersed chich embryonic cardiac cells. Adenosine is involved in the regulation of coronary blood flow, but its mechanism of action is not clear. The present investigation is an attempt to understand the mechanism(s) of uptake of adenosine in dispersed chick embryonic cardiac cells and its relationship to the adenosine hypothesis. Adenosine is readily taken up by these cardiac cells, and a small fraction is incorporated into adenine nucleotides, whereas a major fraction is deaminated to inosine. The mechanism of uptake is different in 12- to 15-day-old chick embryos compared to 16- to 22-day-old embryos. The younger embryo heart cells show the incorporation of adenosine into adenine mononucleotides of the incubation medium as well as all the adenine nucleotides of the cells, whereas the older embryo heart cells show incorporation of adenosine only into the adenine nucleotides of the cells. The isolated cells used in the present study do not leak any significant amounts of adenosine kinase and/or nucleotides, and free adenosine was not found in the cells, even with extracellular concentrations as high as 1 mM. The absence of free adenosine in isolated dispersed cells reflects the activities of adenosine kinase and adenosine deaminase and is compatible with the adenosine hypothesis for the regulation of coronary blood flow."} {"id": "PMID:167592", "title": "Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration.", "content": "The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.", "contents": "Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration. The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system."} {"id": "PMID:167593", "title": "Angiotensin and the hemodynamics of chronic salt deprivation.", "content": "Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance.", "contents": "Angiotensin and the hemodynamics of chronic salt deprivation. Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance."} {"id": "PMID:167594", "title": "Aggregation and release in thrombocytes of the duck.", "content": "Avian thromboyctes are aggregated by a number of substances that cause platelet aggregation, and evidence suggests that this response is related to the release of serotonin (5-hydroxytryptamine, 5-HT) from intracellular granules. In this study duck thrombocytes released 5-HT during collagen-induced aggregation, but thrombocytes incubated with 14C-labeled adenine did not release radioactive adenine nucleotides. These results indicate the existence of a metabolic pool of adenine nucleotides that is separate from released constituents of the cell. No unlabeled adenine compounds were detected in the supernatants of aggregated thrombocytes indicating either the rapid alteration of released nucleotides or the absence of a specific release pool of adenine nucleotides. Finally there is no release of the intracellular enzyme markers, lactate dehydrogenase, beta-glucuronidase, and acid phosphatase, during collagen-induced aggregation. These findings suggest that avian thrombocytes exhibit a specific release reaction and that serotonin acts as the functional counterpart of ADP in platelet aggregation.", "contents": "Aggregation and release in thrombocytes of the duck. Avian thromboyctes are aggregated by a number of substances that cause platelet aggregation, and evidence suggests that this response is related to the release of serotonin (5-hydroxytryptamine, 5-HT) from intracellular granules. In this study duck thrombocytes released 5-HT during collagen-induced aggregation, but thrombocytes incubated with 14C-labeled adenine did not release radioactive adenine nucleotides. These results indicate the existence of a metabolic pool of adenine nucleotides that is separate from released constituents of the cell. No unlabeled adenine compounds were detected in the supernatants of aggregated thrombocytes indicating either the rapid alteration of released nucleotides or the absence of a specific release pool of adenine nucleotides. Finally there is no release of the intracellular enzyme markers, lactate dehydrogenase, beta-glucuronidase, and acid phosphatase, during collagen-induced aggregation. These findings suggest that avian thrombocytes exhibit a specific release reaction and that serotonin acts as the functional counterpart of ADP in platelet aggregation."} {"id": "PMID:167595", "title": "A phylogenetic study of the role of cyclic AMP in lipid synthesis in vertebrates.", "content": "The effect of cyclic AMP on the incorporation of acetate-2-14C into sterols and fatty acid in vitro in slices of liver and intestine was examined in various representatives of the vertebrate group. In no instance was an effect on lipid synthesis noted in intestine. Cyclic AMP exerted no significant effects on hepatic lipogenesis in lower vertebrates, including the nurse shark, catfish, toad, or iguana. However, the nucleotide strongly inhibited the incorporation of acetate-2-14C into fatty acid by the chicken liver. Similar inhibition of fatty acid synthesis was also noted in rat liver, but in this mammalian species hepatic sterol synthesis was also strikingly suppressed by cyclic AMP. Interruption of the enterohepatic circuit in the rat, while enhancing rates of sterol synthesis in both liver and intestine, neither enhanced nor diminished hepatic susceptibility to suppressed sterologenesis by cyclic AMP, nor did it confer on the intestine any newfound capacity for cyclic AMP-regulated lipid synthesis.", "contents": "A phylogenetic study of the role of cyclic AMP in lipid synthesis in vertebrates. The effect of cyclic AMP on the incorporation of acetate-2-14C into sterols and fatty acid in vitro in slices of liver and intestine was examined in various representatives of the vertebrate group. In no instance was an effect on lipid synthesis noted in intestine. Cyclic AMP exerted no significant effects on hepatic lipogenesis in lower vertebrates, including the nurse shark, catfish, toad, or iguana. However, the nucleotide strongly inhibited the incorporation of acetate-2-14C into fatty acid by the chicken liver. Similar inhibition of fatty acid synthesis was also noted in rat liver, but in this mammalian species hepatic sterol synthesis was also strikingly suppressed by cyclic AMP. Interruption of the enterohepatic circuit in the rat, while enhancing rates of sterol synthesis in both liver and intestine, neither enhanced nor diminished hepatic susceptibility to suppressed sterologenesis by cyclic AMP, nor did it confer on the intestine any newfound capacity for cyclic AMP-regulated lipid synthesis."} {"id": "PMID:167596", "title": "Comparison of two five-year follow-up studies: 1948 to 1952 and 1967 to 1972.", "content": "Results of a 5-year follow-up of 100 randomly selected patients committed to a community-oriented mental hospital in 1947 are compared with those of a 5-year follow-up of 100 randomly selected patients admitted to a community-based mental health center in 1967. The data show that both programs were successful in kepping patients with historis of long-standing mental illness in the community, even thought the 1947 group did not receive any modern psychotropic medication. One uoexpected finding of the comparison is the suggestion that these drugs might not be indispensable; in fact, they might actually prolong the social dependency of some discharged patients.", "contents": "Comparison of two five-year follow-up studies: 1948 to 1952 and 1967 to 1972. Results of a 5-year follow-up of 100 randomly selected patients committed to a community-oriented mental hospital in 1947 are compared with those of a 5-year follow-up of 100 randomly selected patients admitted to a community-based mental health center in 1967. The data show that both programs were successful in kepping patients with historis of long-standing mental illness in the community, even thought the 1947 group did not receive any modern psychotropic medication. One uoexpected finding of the comparison is the suggestion that these drugs might not be indispensable; in fact, they might actually prolong the social dependency of some discharged patients."} {"id": "PMID:167597", "title": "Brief transference-focused therapy of hospitalized psychiatric patients.", "content": "A therapeutic approach referred to as brief transference-focused therapy for hospitalized psychiatric patients is discussed with its three key constituents being early selective intervention, the nurturing of positive transference, and the active participation of the patient in determining posthospital treatment. Clinical examples are presented in which these constituents are illustrated. Gains and limitations of this treatment are discussed.", "contents": "Brief transference-focused therapy of hospitalized psychiatric patients. A therapeutic approach referred to as brief transference-focused therapy for hospitalized psychiatric patients is discussed with its three key constituents being early selective intervention, the nurturing of positive transference, and the active participation of the patient in determining posthospital treatment. Clinical examples are presented in which these constituents are illustrated. Gains and limitations of this treatment are discussed."} {"id": "PMID:167599", "title": "Roentgenographic findings in fucosidosis type 2.", "content": "The roentgen findings are described in 2 siblings with fucosidosis Type 2. They have mild dysostosis multiplex with predominant involvement of the spine, pelvis, and femoral capital epiphyses. The roentgen descriptions of the previously reported cases are reviewed. Based on the descriptive data currently available, there are no consistent differences which would permit the distinction of fucosidosis Type 1 from Type 2 on roentgen grounds.", "contents": "Roentgenographic findings in fucosidosis type 2. The roentgen findings are described in 2 siblings with fucosidosis Type 2. They have mild dysostosis multiplex with predominant involvement of the spine, pelvis, and femoral capital epiphyses. The roentgen descriptions of the previously reported cases are reviewed. Based on the descriptive data currently available, there are no consistent differences which would permit the distinction of fucosidosis Type 1 from Type 2 on roentgen grounds."} {"id": "PMID:167600", "title": "Light and electron microscopic study of dysplastic rosette-like structures occurring in the disorganized mature retina.", "content": "Histopathologic examination of six, adult human eyes revealed \"rosette-like\" structures in the retina which appear to have developed after maturation of the retina. These structures resemble dysplastic rosettes which are generally interpreted as a sign of maldevelopment of the retina (retinal dysplasia). The underlying lesions in the eyes of these patients were ocular ischemia, sickle-cell retinopathy, diabetic retinopathy, central retinal vein occlusion, and trauma. It is suggested that a distinction should be made between these degenerative-regressive changes and dysplastic rosettes which represent an abortive attempt of regeneration by germinal cells.", "contents": "Light and electron microscopic study of dysplastic rosette-like structures occurring in the disorganized mature retina. Histopathologic examination of six, adult human eyes revealed \"rosette-like\" structures in the retina which appear to have developed after maturation of the retina. These structures resemble dysplastic rosettes which are generally interpreted as a sign of maldevelopment of the retina (retinal dysplasia). The underlying lesions in the eyes of these patients were ocular ischemia, sickle-cell retinopathy, diabetic retinopathy, central retinal vein occlusion, and trauma. It is suggested that a distinction should be made between these degenerative-regressive changes and dysplastic rosettes which represent an abortive attempt of regeneration by germinal cells."} {"id": "PMID:167614", "title": "Studies on the liver of Xenopus laevis. I. The ultrastructure of the parenchymal cell.", "content": "The liver of Xenopus laevis was examined with electron microscopy. Its structure was found to be markedly different from that of mammals, particularly regarding the morphology of the hepatocytes to be classified as typical. It was established that the main function of such a cell is the storage of glycogen, and further that it possesses only scant organelles and other inclusions. Since this type of cell was found most frequently in the liver of untreated animals, it was designated as normal cell. The fact appears noteworthy that in the normal liver of Xenopus laevis an abundance of cell types occur which are otherwise found to be proliferated under experimental conditions, e.g. cells with pronouncedly augmented RER, enlarged Golgi complexes, increased lipid inclusions etc. This high number of divergent hepatocytes and the fact that all intermediate stages between the individual extremes are present and not to be accounted for by the position of the cell within the liver was interpreted as being the expression of a cyclic passage of the various stages of activity. It is of special interest that augmented degradation of glycogen in the liver cell takes place only during vitellogenesis. Acute and chronic hunger, as well as adaptation to cold, hardly affect the morphology of the normal cell, especially as far as the glycogen is concerned. The possible causes for this are discussed.", "contents": "Studies on the liver of Xenopus laevis. I. The ultrastructure of the parenchymal cell. The liver of Xenopus laevis was examined with electron microscopy. Its structure was found to be markedly different from that of mammals, particularly regarding the morphology of the hepatocytes to be classified as typical. It was established that the main function of such a cell is the storage of glycogen, and further that it possesses only scant organelles and other inclusions. Since this type of cell was found most frequently in the liver of untreated animals, it was designated as normal cell. The fact appears noteworthy that in the normal liver of Xenopus laevis an abundance of cell types occur which are otherwise found to be proliferated under experimental conditions, e.g. cells with pronouncedly augmented RER, enlarged Golgi complexes, increased lipid inclusions etc. This high number of divergent hepatocytes and the fact that all intermediate stages between the individual extremes are present and not to be accounted for by the position of the cell within the liver was interpreted as being the expression of a cyclic passage of the various stages of activity. It is of special interest that augmented degradation of glycogen in the liver cell takes place only during vitellogenesis. Acute and chronic hunger, as well as adaptation to cold, hardly affect the morphology of the normal cell, especially as far as the glycogen is concerned. The possible causes for this are discussed."} {"id": "PMID:167615", "title": "Fine structure of the interrenal cell in the quail and the pigeon.", "content": "The ultrastructural characteristics of the interrenal cell were investigated in the quail and the pigeon after fixation by intravascular abdominal perfusion. There is no significant fine structural difference between cells belonging to subcapsular and central regions of the gland. The interrenal cell in both species possesses nuclear bodies, polymorphic mitochondria with tubulo-vesicular cristae and tubular crystalline inclusions, considerable amounts of endoplasmic reticulum, ergastoplasm, a well developed Golgi apparatus, coated vesicles, microtubules, filaments, cilia, ribosomes, a profusion of liposomes, dense bodies with varied inner structure, pinocytic invaginations of cell membrane and intercellular attachment devices. The pigeon adrenorcortical cell also possesses intranuclear lipidlike inclusions and fibrous bundle (this being never recorded in adrenocortical cell), annulate lamellae, and a variety of cytosomes, probably lipofucsin in nature. The significance and cytophysiological role of various organelles and inclusions have been discussed in the light of earlier data obtained on avian adrenocortical cells.", "contents": "Fine structure of the interrenal cell in the quail and the pigeon. The ultrastructural characteristics of the interrenal cell were investigated in the quail and the pigeon after fixation by intravascular abdominal perfusion. There is no significant fine structural difference between cells belonging to subcapsular and central regions of the gland. The interrenal cell in both species possesses nuclear bodies, polymorphic mitochondria with tubulo-vesicular cristae and tubular crystalline inclusions, considerable amounts of endoplasmic reticulum, ergastoplasm, a well developed Golgi apparatus, coated vesicles, microtubules, filaments, cilia, ribosomes, a profusion of liposomes, dense bodies with varied inner structure, pinocytic invaginations of cell membrane and intercellular attachment devices. The pigeon adrenorcortical cell also possesses intranuclear lipidlike inclusions and fibrous bundle (this being never recorded in adrenocortical cell), annulate lamellae, and a variety of cytosomes, probably lipofucsin in nature. The significance and cytophysiological role of various organelles and inclusions have been discussed in the light of earlier data obtained on avian adrenocortical cells."} {"id": "PMID:167616", "title": "Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.", "content": "To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.", "contents": "Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets. To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume."} {"id": "PMID:167617", "title": "Inhalation anesthetics and cytochrome P-450-dependent reactions in rat liver microsomes.", "content": "The activities of liver microsomal enzymes were studied in preparations from unanesthetized rats and rats anesthetized for one hour with nitrous oxide, diethyl ether, halothane or chloroform. Most of the enzymes studied were cytochrome P-450-dependent oxygenases that hydroxylate endogenous substrates. The other microsomal enzymes, assayed for comparison, included the cytochrome P-450-dependent aminopyrine demethylase, glucose-6-phosphatase, a dehydrogenase, and NADPH-cytochrome P-450 reductase. No anesthetic was associated with a significant change in activity of any enzyme studied. In rats pretreated with phenobarbital no anesthetic except chloroform changed enzymic activity. All hydroxylations were inhibited markedly by chloroform, as were a microsomal dehydrogenation, hydrolysis of glucose-6-phosphate, and NADPH-cytochrome P-450 reductase activity. Administration of alpha-tocopherol did not prevent the inhibition associated with chloroform in phenobarbital-induced animals. It is concluded that cytochrome P-450-dependent hydroxylations involved in metabolic processes normally proceeding in the endoplasmic reticulum of the liver are not permanently affected by the anesthetics used in this study. The inhibitory effect of chloroform after pretreatment with phenobarbital is unspecific and affects a large number of different microsomal enzymes. Evidence that mechanisms other than lipid peroxidation may be responsible for the toxic effects of chloroform in the liver is presented.", "contents": "Inhalation anesthetics and cytochrome P-450-dependent reactions in rat liver microsomes. The activities of liver microsomal enzymes were studied in preparations from unanesthetized rats and rats anesthetized for one hour with nitrous oxide, diethyl ether, halothane or chloroform. Most of the enzymes studied were cytochrome P-450-dependent oxygenases that hydroxylate endogenous substrates. The other microsomal enzymes, assayed for comparison, included the cytochrome P-450-dependent aminopyrine demethylase, glucose-6-phosphatase, a dehydrogenase, and NADPH-cytochrome P-450 reductase. No anesthetic was associated with a significant change in activity of any enzyme studied. In rats pretreated with phenobarbital no anesthetic except chloroform changed enzymic activity. All hydroxylations were inhibited markedly by chloroform, as were a microsomal dehydrogenation, hydrolysis of glucose-6-phosphate, and NADPH-cytochrome P-450 reductase activity. Administration of alpha-tocopherol did not prevent the inhibition associated with chloroform in phenobarbital-induced animals. It is concluded that cytochrome P-450-dependent hydroxylations involved in metabolic processes normally proceeding in the endoplasmic reticulum of the liver are not permanently affected by the anesthetics used in this study. The inhibitory effect of chloroform after pretreatment with phenobarbital is unspecific and affects a large number of different microsomal enzymes. Evidence that mechanisms other than lipid peroxidation may be responsible for the toxic effects of chloroform in the liver is presented."} {"id": "PMID:167620", "title": "Virus-like particles in buffy coat cells of normal goats and goats infected with progressive pneumonia virus.", "content": "By electron microscopy, virus-like particles (VLP) were seen in neutrophils and lymphocytes from buffy coats prepared from 5 goats inoculated with progressive pneumonia virus (PPV) and 3 noninoculated goats. The VLP were 80 to 120 nm in diameter, limited by a unit membrane, and resembled PPV, visna virus, and other members of the oncornavirus family. Some VLP seemed to have electron-dense nucleoids and external spikes. In neutrophils, VLP were observed budding into vacuoles; rarely, intravacuolar clusters were seen. In lymphocytes, VLP were seen in vacuoles. Free VLP and budding of VLP from external cell surfaces were not seen. In vitro incubation of buffy coat cells with mitogens did not affect the frequency of VLP. Although the VLP are similar to PPV, the exact nature of the particles and their relationship to PPV is not clearly understood.", "contents": "Virus-like particles in buffy coat cells of normal goats and goats infected with progressive pneumonia virus. By electron microscopy, virus-like particles (VLP) were seen in neutrophils and lymphocytes from buffy coats prepared from 5 goats inoculated with progressive pneumonia virus (PPV) and 3 noninoculated goats. The VLP were 80 to 120 nm in diameter, limited by a unit membrane, and resembled PPV, visna virus, and other members of the oncornavirus family. Some VLP seemed to have electron-dense nucleoids and external spikes. In neutrophils, VLP were observed budding into vacuoles; rarely, intravacuolar clusters were seen. In lymphocytes, VLP were seen in vacuoles. Free VLP and budding of VLP from external cell surfaces were not seen. In vitro incubation of buffy coat cells with mitogens did not affect the frequency of VLP. Although the VLP are similar to PPV, the exact nature of the particles and their relationship to PPV is not clearly understood."} {"id": "PMID:167621", "title": "Comparison of the characteristics of avian reoviruses isolated from the digestive and respiratory tract, with viruses isolated from the synovia.", "content": "Two-week-old gnotobiotic chicks were inoculated in the foot pad with viruses isolated from synovia and synovial membrane-WVU 1464-29H, WVU 1675, WVU 2937, WVU 2986, and WVU 71-212; from digestive tract-reoviruses 24, 25, and 59; or from respiratory tract-reovirus Fahey-Crawley (FC). All viruses induced swelling of the foot pad and inflammatory changes of synovial membrane. Serum from virus-infected chicks had a common agar gel precipitin (AGP) line. On the basis of the plaque-reduction test in primary chicken kidney (PCK) cells, the viruses were classified into 4 major serotypes. All viruses produced cytopathic effects (CPE) in primary chicken tissue cultures. Other than reovirus FC and WVU 1464-29H, all viruses produced CPE in the Vero cell line.", "contents": "Comparison of the characteristics of avian reoviruses isolated from the digestive and respiratory tract, with viruses isolated from the synovia. Two-week-old gnotobiotic chicks were inoculated in the foot pad with viruses isolated from synovia and synovial membrane-WVU 1464-29H, WVU 1675, WVU 2937, WVU 2986, and WVU 71-212; from digestive tract-reoviruses 24, 25, and 59; or from respiratory tract-reovirus Fahey-Crawley (FC). All viruses induced swelling of the foot pad and inflammatory changes of synovial membrane. Serum from virus-infected chicks had a common agar gel precipitin (AGP) line. On the basis of the plaque-reduction test in primary chicken kidney (PCK) cells, the viruses were classified into 4 major serotypes. All viruses produced cytopathic effects (CPE) in primary chicken tissue cultures. Other than reovirus FC and WVU 1464-29H, all viruses produced CPE in the Vero cell line."} {"id": "PMID:167623", "title": "An unusual case of feline leukemia and an associated syncytium-forming virus.", "content": "A 3-year-old female Siamese cat was admitted to a local animal hospital with a history of recent extreme lethargy and anorexia. A hemorrhagic tumor was removed from an area of oral buccal skin and diagnosed histopathologically as lymphosarcoma. Rapid physical deterioration occurred, and the cat became moribund 2 weeks after surgical operation. Necropsy revealed at least 200 spherical hemorrhagic neoplastic nodules attached to the omentum, mesentery, and peritoneum. Examination of histopathologic sections confirmed the striking characteristics of an extremely vascular and highly invasive malignant lymphoma, which was designated feline tumor No. 01 (FeT-01). There was no evidence of peripheral blood leukemia. Electron microscopic examination of tumor tissue revealed numerous viral particles having characteristics common to both feline leukemia virus (FeLV) and feline syncytium-forming virus (FeSFV). Primary cells and cultures propagated from tumor tissue were found to be negative or weakly positive for group-specific (gs) antigen by radioimmunoassay but strongly positive when assayed by indirect immunofluorescence. Co-cultivation of cells from tumor tissue, with normal prescreened feline embryo cells, revealed the presence of numerous FeSFV-like viral particles in the absence of C-type virus. A FeSFV was isolated from these passaged cells, with characteristics similar to FeSFV isolates previously described in the literature. The apparent presence of FeSFV in lymphosarcomatous tissue and the apparent absence of FeLV C-type particles in passaged cells indicate the need to make a more intensive study of the FeSFV group of viruses and the possible etiologic relationship to feline malignancies.", "contents": "An unusual case of feline leukemia and an associated syncytium-forming virus. A 3-year-old female Siamese cat was admitted to a local animal hospital with a history of recent extreme lethargy and anorexia. A hemorrhagic tumor was removed from an area of oral buccal skin and diagnosed histopathologically as lymphosarcoma. Rapid physical deterioration occurred, and the cat became moribund 2 weeks after surgical operation. Necropsy revealed at least 200 spherical hemorrhagic neoplastic nodules attached to the omentum, mesentery, and peritoneum. Examination of histopathologic sections confirmed the striking characteristics of an extremely vascular and highly invasive malignant lymphoma, which was designated feline tumor No. 01 (FeT-01). There was no evidence of peripheral blood leukemia. Electron microscopic examination of tumor tissue revealed numerous viral particles having characteristics common to both feline leukemia virus (FeLV) and feline syncytium-forming virus (FeSFV). Primary cells and cultures propagated from tumor tissue were found to be negative or weakly positive for group-specific (gs) antigen by radioimmunoassay but strongly positive when assayed by indirect immunofluorescence. Co-cultivation of cells from tumor tissue, with normal prescreened feline embryo cells, revealed the presence of numerous FeSFV-like viral particles in the absence of C-type virus. A FeSFV was isolated from these passaged cells, with characteristics similar to FeSFV isolates previously described in the literature. The apparent presence of FeSFV in lymphosarcomatous tissue and the apparent absence of FeLV C-type particles in passaged cells indicate the need to make a more intensive study of the FeSFV group of viruses and the possible etiologic relationship to feline malignancies."} {"id": "PMID:167624", "title": "Comparative pathogenicity of avian encephalomyelitis viruses in chicken embryos.", "content": "Multiplications of wild, various embryo-adapting and completely embryo-adapted avian encephalomyelitis (AE) viruses in chicken embryos were compared by the fluorescent-antibody technique (FAT). With a wild AE virus, viral antigens were randomly seen in the central nervous system (CNS), appearing least often in the cerebellum. Other organs seldom became test positive, except for heart and kidney. Even with 4 chicken brain-passaged viruses in the process of embryo adaptation, there was little augmentation of antigens except in the alimentary tract. However, the 2 midpassage viruses showed a peculiar localization of antigens in the white matter of the lumbosacral cord, together with the appearance of test-positive spinal ganglion cells. With 2 strains of embryo-adapted AE virus, the antigens appeared first in the spinal ganglion cells and secondly in the lumbosacral cord and then spread to the cerebrum. Subsequently, clinical signs of AE were evident. This peculiar invasion order was a prominent feature.", "contents": "Comparative pathogenicity of avian encephalomyelitis viruses in chicken embryos. Multiplications of wild, various embryo-adapting and completely embryo-adapted avian encephalomyelitis (AE) viruses in chicken embryos were compared by the fluorescent-antibody technique (FAT). With a wild AE virus, viral antigens were randomly seen in the central nervous system (CNS), appearing least often in the cerebellum. Other organs seldom became test positive, except for heart and kidney. Even with 4 chicken brain-passaged viruses in the process of embryo adaptation, there was little augmentation of antigens except in the alimentary tract. However, the 2 midpassage viruses showed a peculiar localization of antigens in the white matter of the lumbosacral cord, together with the appearance of test-positive spinal ganglion cells. With 2 strains of embryo-adapted AE virus, the antigens appeared first in the spinal ganglion cells and secondly in the lumbosacral cord and then spread to the cerebrum. Subsequently, clinical signs of AE were evident. This peculiar invasion order was a prominent feature."} {"id": "PMID:167625", "title": "Cross-reactions of normal bovine serums to foot-and-mouth disease virus in plaque-reduction neutralization and radial immunodiffusion.", "content": "Serums from 150 cattle with no known exposure to foot-and-mouth disease (FMD) virus were tested by both the plaque-reduction neutralization (PRN) technique and the radial immunodiffusion (RID) technique to evaluate the significance and the extent of cross-reactions in these tests. Serums from 30 cattle from each of 5 locations were tested against representative viruses of each of the 7 types of FMD virus. High levels of cross-reactions with both the RID and PRN techniques were found in serums of specific groups. Higher levels of cross-reactions were noted for Asia, SAT I, SAT II, and SAT III than for A, O, or C viruses with the PRN technique, and higher levels for SAT II and SAT III with the RID technique. The reactions for most serums appeared to be quite specific; a given serum was often reactive with only 1 or 2 viruses.", "contents": "Cross-reactions of normal bovine serums to foot-and-mouth disease virus in plaque-reduction neutralization and radial immunodiffusion. Serums from 150 cattle with no known exposure to foot-and-mouth disease (FMD) virus were tested by both the plaque-reduction neutralization (PRN) technique and the radial immunodiffusion (RID) technique to evaluate the significance and the extent of cross-reactions in these tests. Serums from 30 cattle from each of 5 locations were tested against representative viruses of each of the 7 types of FMD virus. High levels of cross-reactions with both the RID and PRN techniques were found in serums of specific groups. Higher levels of cross-reactions were noted for Asia, SAT I, SAT II, and SAT III than for A, O, or C viruses with the PRN technique, and higher levels for SAT II and SAT III with the RID technique. The reactions for most serums appeared to be quite specific; a given serum was often reactive with only 1 or 2 viruses."} {"id": "PMID:167627", "title": "Pulmonary tuberculosis and coexisting carcinoma: a 10-year experience and review of the literature.", "content": "Of 7,986 patients admitted to Mount Wilson State Hospital for Pulmonary Diseases between 1960 and 1970, 72 were proven to have coexisting pulmonary tuberculosis and bronchogenic carcinoma. The patients usually were in the older age group, and usually smoked. There was a high predilection for the tumor to occur in the upper lobes. Active tuberculosis was present in 50 per cent of the patients and tumor and tuberculosis was present in the same area 80 per cent of the time. Cell diagnosis was possible in 60 per cent of the patients without thoracotomy. Diagnosis was usually made late in the course of the disease and therapeutic results were poor. Only 13 patients were operable and only four are presently alive. Earlier recognition is vital to adequate treatment. A plan for earlier recognition based on a high degree of suspicion is presented.", "contents": "Pulmonary tuberculosis and coexisting carcinoma: a 10-year experience and review of the literature. Of 7,986 patients admitted to Mount Wilson State Hospital for Pulmonary Diseases between 1960 and 1970, 72 were proven to have coexisting pulmonary tuberculosis and bronchogenic carcinoma. The patients usually were in the older age group, and usually smoked. There was a high predilection for the tumor to occur in the upper lobes. Active tuberculosis was present in 50 per cent of the patients and tumor and tuberculosis was present in the same area 80 per cent of the time. Cell diagnosis was possible in 60 per cent of the patients without thoracotomy. Diagnosis was usually made late in the course of the disease and therapeutic results were poor. Only 13 patients were operable and only four are presently alive. Earlier recognition is vital to adequate treatment. A plan for earlier recognition based on a high degree of suspicion is presented."} {"id": "PMID:167628", "title": "Postpartum hemorrhage into a large nonfunctioning islet cell tumor of the pancreas.", "content": "A case of postpartum hemorrhage into a nonfunctioning islet cell tumor of the pancreas is presented. The manifestations and surgical management of this tumor are discussed. The incidence and pathological significance of such a tumor are examined.", "contents": "Postpartum hemorrhage into a large nonfunctioning islet cell tumor of the pancreas. A case of postpartum hemorrhage into a nonfunctioning islet cell tumor of the pancreas is presented. The manifestations and surgical management of this tumor are discussed. The incidence and pathological significance of such a tumor are examined."} {"id": "PMID:167630", "title": "Current and future concepts of lung cancer.", "content": "We discuss here some of the last decade's diagnostic and therapeutic advances in the treatment of lung cancer, as well as current and future research objectives. Roentgenographs from selected patients illustrate the natural history of lung cancer. We present perspectives concerning selection from the growing diagnostic armamentarium, with comments upon early detection and localization of \"occult\" cancers with the help of flexible bronchoscopy. Operative approaches have changed over the past 4 decades; we review how and why they evolved, including perspectives concerning mediastinoscopy. There is a presentation on a radiotherapeutic research approach to oat-cell cancers and the current status of immunotherapy. Such issues as animal models available for lung cancer research emerge in the general discussion, and it becomes clear that lung cancer merits a truly interdisciplinary approach in order to bring meaningful advances to the patient's bedside.", "contents": "Current and future concepts of lung cancer. We discuss here some of the last decade's diagnostic and therapeutic advances in the treatment of lung cancer, as well as current and future research objectives. Roentgenographs from selected patients illustrate the natural history of lung cancer. We present perspectives concerning selection from the growing diagnostic armamentarium, with comments upon early detection and localization of \"occult\" cancers with the help of flexible bronchoscopy. Operative approaches have changed over the past 4 decades; we review how and why they evolved, including perspectives concerning mediastinoscopy. There is a presentation on a radiotherapeutic research approach to oat-cell cancers and the current status of immunotherapy. Such issues as animal models available for lung cancer research emerge in the general discussion, and it becomes clear that lung cancer merits a truly interdisciplinary approach in order to bring meaningful advances to the patient's bedside."} {"id": "PMID:167631", "title": "Polymyxin B reactions, IgE antibody, and T-cell deficiency. Immunochemical studies in a patient after bone marrow transplantation.", "content": "A patient with aplastic anemia was immunosuppressed with cyclophosphamide and transplanted with allogenic bone marrow. While lacking demonstrable T-cell activity posttransplantation, he developed a generalized macular erythematous eruption and fever, clinically attributed to intranasal polymyxin B. A specific IgE antibody, demonstrated by direct skin testing, Prausnitz-Kustner passive transfer, and indirect passive hemagglutination was temporally related to the reaction. Discontinuation of the drug led to prompt defervescence and resolution of the drug eruption.", "contents": "Polymyxin B reactions, IgE antibody, and T-cell deficiency. Immunochemical studies in a patient after bone marrow transplantation. A patient with aplastic anemia was immunosuppressed with cyclophosphamide and transplanted with allogenic bone marrow. While lacking demonstrable T-cell activity posttransplantation, he developed a generalized macular erythematous eruption and fever, clinically attributed to intranasal polymyxin B. A specific IgE antibody, demonstrated by direct skin testing, Prausnitz-Kustner passive transfer, and indirect passive hemagglutination was temporally related to the reaction. Discontinuation of the drug led to prompt defervescence and resolution of the drug eruption."} {"id": "PMID:167644", "title": "Effectiveness of neomycin and polymyxin ointments: prevention of Staphylococcus Aureus keratitis in rabbits.", "content": "Combinations of neomycin sulfate and polymyxin B sulfate are commonly used in ophthalmic ointments for the treatment or the prevention of bacterial keratoconjunctivitis. In this study we evaluated the effectiveness of various ointments containing these two antibiotics, alone and in combination, in preventing Staphylococcus aureus keratitis in rabbits. Rabbit eyes were infected by intracorneal inoculation, treated topically with ointment and graded by gross observation 24 hours after inoculation. Treatment with ointments containing neomycin alone offered significant protection against these corneal infections. The polymyxin B ointments, as well as the vehicle controls, were ineffective in preventing S aureus infections in the rabbit eyes. However, by far, the most effective ointment formulations tested were the combination ointments and specifically those containing 1.75-3.50 mg neomycin and 3,000-6,000 units polymycin B per gram of ointment.", "contents": "Effectiveness of neomycin and polymyxin ointments: prevention of Staphylococcus Aureus keratitis in rabbits. Combinations of neomycin sulfate and polymyxin B sulfate are commonly used in ophthalmic ointments for the treatment or the prevention of bacterial keratoconjunctivitis. In this study we evaluated the effectiveness of various ointments containing these two antibiotics, alone and in combination, in preventing Staphylococcus aureus keratitis in rabbits. Rabbit eyes were infected by intracorneal inoculation, treated topically with ointment and graded by gross observation 24 hours after inoculation. Treatment with ointments containing neomycin alone offered significant protection against these corneal infections. The polymyxin B ointments, as well as the vehicle controls, were ineffective in preventing S aureus infections in the rabbit eyes. However, by far, the most effective ointment formulations tested were the combination ointments and specifically those containing 1.75-3.50 mg neomycin and 3,000-6,000 units polymycin B per gram of ointment."} {"id": "PMID:167650", "title": "Effects of anesthesia on intermediary metabolism.", "content": "Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done.", "contents": "Effects of anesthesia on intermediary metabolism. Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done."} {"id": "PMID:167654", "title": "Neuroregulators and sleep mechanisms.", "content": "Information which has emerged thus far relates to the overall transmitter mechanisms of sleep. The data, while conflicting, point to the involvement of many neuroregulators at numerous integrative levels of the process. However the long term question still remain: what triggers and maintain sleep, what stops sleep, what occurs to the body and brain during sleep--in essence, why sleep? These questions are now problems for behavioral neurochemists, whereas in a previous era, they were problems for philosophers. Unfortunately, our answers to date, while in another idiom, have hardly been more complete or satisfying. To answer these questions, it will be necessary to understand, in detail, the manner in which neurobiochemical processes relate to the functional physiology of sleep. Although existing studies have given invaluable insight into the neurochemical anatomy of sleep, we have only recently acquired the technical and biochemical expertise necessary to investigate sleep as it occurs normally. Future research must focus on the dynamic changes associated with the regulatory mechanisms of neurotransmitters. Many questions can be asked. With sleep transitions, what changes occur in transmitter content, synthesis, or release? Are there changes in metabolic pathways, reflecting a shift from intra- to interneuronal metabolism? What changes occur in pre- and postsynaptic neurotransmitter receptors to affect sensitivity? What constraints do genetic (245) and environmental (246) factors impose upon these mechanisms? Knowledge of such parameters will allow us to construct more complete models of the neuroregulatory basis of sleep and waking. However, as we acquire this knowledge, we must avoid the temptation of assuming causation when the evidence merely shows correlation. Neuroregulation are involved in the control of number different behaviors; and, at present, we have few, if any, methods of establishing causative links between a specific neuroregulator and a specific behavioral state. Yet, even without an understanding of what \"causes\" sleep, we may be able to develop pharmacological agents which permits discrete alteration of sleep mechanisms in a more physiological and specific manner. This potential for manipulation of sleep is of obvious importance in illnesses such as insomnia, narcolepsy, and sleep apnea (247, 248). In addition, it may be valuable in the treatment of such conditions as psychosis and depression, where sleep disturbances are an important component of the illness. For example, delirium tremens might be best understood as a psychotic episode which is the result of an aspect of sleep emerging into wakefulness. The range and breadth of both the basic questions and the potential application of sleep research portend an exciting future for this field.", "contents": "Neuroregulators and sleep mechanisms. Information which has emerged thus far relates to the overall transmitter mechanisms of sleep. The data, while conflicting, point to the involvement of many neuroregulators at numerous integrative levels of the process. However the long term question still remain: what triggers and maintain sleep, what stops sleep, what occurs to the body and brain during sleep--in essence, why sleep? These questions are now problems for behavioral neurochemists, whereas in a previous era, they were problems for philosophers. Unfortunately, our answers to date, while in another idiom, have hardly been more complete or satisfying. To answer these questions, it will be necessary to understand, in detail, the manner in which neurobiochemical processes relate to the functional physiology of sleep. Although existing studies have given invaluable insight into the neurochemical anatomy of sleep, we have only recently acquired the technical and biochemical expertise necessary to investigate sleep as it occurs normally. Future research must focus on the dynamic changes associated with the regulatory mechanisms of neurotransmitters. Many questions can be asked. With sleep transitions, what changes occur in transmitter content, synthesis, or release? Are there changes in metabolic pathways, reflecting a shift from intra- to interneuronal metabolism? What changes occur in pre- and postsynaptic neurotransmitter receptors to affect sensitivity? What constraints do genetic (245) and environmental (246) factors impose upon these mechanisms? Knowledge of such parameters will allow us to construct more complete models of the neuroregulatory basis of sleep and waking. However, as we acquire this knowledge, we must avoid the temptation of assuming causation when the evidence merely shows correlation. Neuroregulation are involved in the control of number different behaviors; and, at present, we have few, if any, methods of establishing causative links between a specific neuroregulator and a specific behavioral state. Yet, even without an understanding of what \"causes\" sleep, we may be able to develop pharmacological agents which permits discrete alteration of sleep mechanisms in a more physiological and specific manner. This potential for manipulation of sleep is of obvious importance in illnesses such as insomnia, narcolepsy, and sleep apnea (247, 248). In addition, it may be valuable in the treatment of such conditions as psychosis and depression, where sleep disturbances are an important component of the illness. For example, delirium tremens might be best understood as a psychotic episode which is the result of an aspect of sleep emerging into wakefulness. The range and breadth of both the basic questions and the potential application of sleep research portend an exciting future for this field."} {"id": "PMID:167658", "title": "Effect of calcium and magnesium ions on the susceptibility of Pseudomonas species to tetracycline, gentamicin polymyxin B, and carbenicillin.", "content": "The effect of calcium and magnesium on the susceptibility of 13 species of Pseudomonas to tetracycline, gentamicin, polymyxin B, and carbenicillin was measured. The majority of the minimum inhibitory concentrations (MICs) of these antibiotics was increased if these cations were added to the test media. The increases in MICs caused by calcium or magnesium were similar, but the combination of both ions generally caused a greater change than either alone. Although the MIC of polymyxin B was most affected by calcium and magnesium, its interpretive susceptibilities (i.e., whether susceptible or resistant) were least changed. Susceptibility tests on Pseudomonas species probably should be done with Muller-Hinton broth supplemented with physiological concentrations of calcium and magnesium to better approximate the in vivo activity of these antibiotics. When the susceptibility tests were performed with Mueller-Hinton agar, the MICs were slightly less than those obtained with Mueller-Hinton broth supplemented with both cations but greater than those obtained with Mueller-Hinton broth supplemented with individual cations.", "contents": "Effect of calcium and magnesium ions on the susceptibility of Pseudomonas species to tetracycline, gentamicin polymyxin B, and carbenicillin. The effect of calcium and magnesium on the susceptibility of 13 species of Pseudomonas to tetracycline, gentamicin, polymyxin B, and carbenicillin was measured. The majority of the minimum inhibitory concentrations (MICs) of these antibiotics was increased if these cations were added to the test media. The increases in MICs caused by calcium or magnesium were similar, but the combination of both ions generally caused a greater change than either alone. Although the MIC of polymyxin B was most affected by calcium and magnesium, its interpretive susceptibilities (i.e., whether susceptible or resistant) were least changed. Susceptibility tests on Pseudomonas species probably should be done with Muller-Hinton broth supplemented with physiological concentrations of calcium and magnesium to better approximate the in vivo activity of these antibiotics. When the susceptibility tests were performed with Mueller-Hinton agar, the MICs were slightly less than those obtained with Mueller-Hinton broth supplemented with both cations but greater than those obtained with Mueller-Hinton broth supplemented with individual cations."} {"id": "PMID:167659", "title": "Inhibition of the growth of hemadsorption 2 virus by three acyl derivatives of amino acids.", "content": "Three acyl derivatives of amino acids, dicarbobenzoxy-l-lysine sodium, carbobenzoxy-l-aspartic acid-beta-benzyl ester potassium, and N-3-phenylpropionyl-S-benzyl-l-cysteine potassium inhibit the growth of parainfluenza 1 (hemadsorption 2) virus. The growth of simian virus 40, vaccinia, poliomyelitis type 1, Semliki Forest, Eastern equine encephalitis, and Western equine encephalitis viruses was not affected by these compounds. Four other acyl derivatives of amino acids did not inhibit the growth of any of the viruses tested.", "contents": "Inhibition of the growth of hemadsorption 2 virus by three acyl derivatives of amino acids. Three acyl derivatives of amino acids, dicarbobenzoxy-l-lysine sodium, carbobenzoxy-l-aspartic acid-beta-benzyl ester potassium, and N-3-phenylpropionyl-S-benzyl-l-cysteine potassium inhibit the growth of parainfluenza 1 (hemadsorption 2) virus. The growth of simian virus 40, vaccinia, poliomyelitis type 1, Semliki Forest, Eastern equine encephalitis, and Western equine encephalitis viruses was not affected by these compounds. Four other acyl derivatives of amino acids did not inhibit the growth of any of the viruses tested."} {"id": "PMID:167660", "title": "Growth curves of anaerobic bacteria in solid media.", "content": "Simple pour plate and spectrophotometric techniques for the evaluation of growth curves of several anaerobic bacteria on solid media are described. Three basic patterns of anaerobic growth were observed. The curves obtained were very reproducible when studied on separate occasions. The curves obtained by spectrophotometric measurement were comparable to those obtained by the pour plate method, especially when a large bacterial inoculum was used. Limitations in the interpretation of the results are discussed. The methods and principles reported could provide the basis for the determination of bacterial growth on solid media using other organisms and different experimental conditions.", "contents": "Growth curves of anaerobic bacteria in solid media. Simple pour plate and spectrophotometric techniques for the evaluation of growth curves of several anaerobic bacteria on solid media are described. Three basic patterns of anaerobic growth were observed. The curves obtained were very reproducible when studied on separate occasions. The curves obtained by spectrophotometric measurement were comparable to those obtained by the pour plate method, especially when a large bacterial inoculum was used. Limitations in the interpretation of the results are discussed. The methods and principles reported could provide the basis for the determination of bacterial growth on solid media using other organisms and different experimental conditions."} {"id": "PMID:167661", "title": "Effects of lead on the lipid composition of Micrococcus luteus cells.", "content": "Micrococcus luteus cells cultivated in medium containing lead salts exhibited a sequence of changes in the quantity of total cellular lipids with essentially no changes from normal cellular yields. The lipid composition of cells cultivated one to four times was moderately decreased (phase I) whereas that of cells cultivated five to six times was reduced by as much as 50% (phase II). Cells cultivated more than six times in lead-containing media had progressively greater quantities of lipid (phase III) approaching that found in control cells. These cells with reestablished lipid contents showed no further effects from more prolonged exposure to lead salts. Chromatographic studies of total lipids of cells of each lipid phase revealed relatively complete lipid compositions. These results indicated that lead is apparently affecting a common biochemical parameter in the biosynthesis of lipids of lipid phase II cells. Changes in the relative quantities of individual components were observed in both the nonpolar and polar lipids in each lipid phase. The most notable changes were the decrease in aliphatic hydrocarbons with concomitant increases in the diglycerides and components identified as a complex family of ketones. Microscopy examinations of control and lead-treated cells revealed electron dense inclusion bodies in membrane fragments in only lead-treated cells.", "contents": "Effects of lead on the lipid composition of Micrococcus luteus cells. Micrococcus luteus cells cultivated in medium containing lead salts exhibited a sequence of changes in the quantity of total cellular lipids with essentially no changes from normal cellular yields. The lipid composition of cells cultivated one to four times was moderately decreased (phase I) whereas that of cells cultivated five to six times was reduced by as much as 50% (phase II). Cells cultivated more than six times in lead-containing media had progressively greater quantities of lipid (phase III) approaching that found in control cells. These cells with reestablished lipid contents showed no further effects from more prolonged exposure to lead salts. Chromatographic studies of total lipids of cells of each lipid phase revealed relatively complete lipid compositions. These results indicated that lead is apparently affecting a common biochemical parameter in the biosynthesis of lipids of lipid phase II cells. Changes in the relative quantities of individual components were observed in both the nonpolar and polar lipids in each lipid phase. The most notable changes were the decrease in aliphatic hydrocarbons with concomitant increases in the diglycerides and components identified as a complex family of ketones. Microscopy examinations of control and lead-treated cells revealed electron dense inclusion bodies in membrane fragments in only lead-treated cells."} {"id": "PMID:167662", "title": "Comparative study of four microporous filters for concentrating viruses from drinking water.", "content": "Four microporous virus-absorbent filter media for recovering low levels of virus from 380 liters of drinking water were compared. In addition two of the filter media were compared with 1,900 liters of drinking water. The filter media evaluated were MF nitrocellulose membranes (293 mm), AA Cox M-780 epoxy-fiberglass-asbestos disks (267 mm), K-27 yarn-wound fiberglass cartridges + AA Cox M-780 disks (127 mm), and Balston epoxy-fiberglass tubes (24.5 by 63.5 mm). The filters were used to concentrate seeded poliovirus from 380 liters of finished drinking water. Sodium thiosulfate was added to the drinking water to neutralize chlorine, and hydrochloric acid was added to adjust the pH to 3.5. Virus was eluted from the filters with glycine-NaOH buffer at pH 11.5. In terms of virus recovery efficiency, the filter media ranked Balston greater than Cox 267-mm greater than MF 293-mm congruent to K-27 + Cox 127-mm, but differences were slight. The Balston filters and holders were also superior to the other systems in terms of size, weight, cost, and handling factors. Experiments with 2- and 8-mum porosity Balston filters showed no statistically significant difference in virus recovery. Virus was readily detected by the Balston and the MF 293-mm systems at input levels of 12 to 22 PFU/1,900 liters. Preliminary experiments indicated that an elution pH lower than 11.5 may be satisfactory.", "contents": "Comparative study of four microporous filters for concentrating viruses from drinking water. Four microporous virus-absorbent filter media for recovering low levels of virus from 380 liters of drinking water were compared. In addition two of the filter media were compared with 1,900 liters of drinking water. The filter media evaluated were MF nitrocellulose membranes (293 mm), AA Cox M-780 epoxy-fiberglass-asbestos disks (267 mm), K-27 yarn-wound fiberglass cartridges + AA Cox M-780 disks (127 mm), and Balston epoxy-fiberglass tubes (24.5 by 63.5 mm). The filters were used to concentrate seeded poliovirus from 380 liters of finished drinking water. Sodium thiosulfate was added to the drinking water to neutralize chlorine, and hydrochloric acid was added to adjust the pH to 3.5. Virus was eluted from the filters with glycine-NaOH buffer at pH 11.5. In terms of virus recovery efficiency, the filter media ranked Balston greater than Cox 267-mm greater than MF 293-mm congruent to K-27 + Cox 127-mm, but differences were slight. The Balston filters and holders were also superior to the other systems in terms of size, weight, cost, and handling factors. Experiments with 2- and 8-mum porosity Balston filters showed no statistically significant difference in virus recovery. Virus was readily detected by the Balston and the MF 293-mm systems at input levels of 12 to 22 PFU/1,900 liters. Preliminary experiments indicated that an elution pH lower than 11.5 may be satisfactory."} {"id": "PMID:167663", "title": "Gardner-Diamond syndrome with multiple glomus tumors.", "content": "The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. The diagnosis of multiple glomus tumors was confirmed by biopsy, and the Gardner-Diamond syndrome was confirmed by reproduction of the painful purpura with the intradermal injection of the patient's sonicated erythrocytes.", "contents": "Gardner-Diamond syndrome with multiple glomus tumors. The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. The diagnosis of multiple glomus tumors was confirmed by biopsy, and the Gardner-Diamond syndrome was confirmed by reproduction of the painful purpura with the intradermal injection of the patient's sonicated erythrocytes."} {"id": "PMID:167664", "title": "Calcium balance in children treated with diphosphonates.", "content": "Serial mineral balances have been obtained in 3 children undergoing therapy with EHDP (ethane-1-hydroxy-1, 1-diphosphonate) for diseases involving ectopic calcification. Although clinical outcome was not uniformly satisfactory, all cases showed an overall reduction in calcium balance. This was due to increased faecal excretion of calcium and was most marked after a long duration of therapy. Although these results conflict with reported experience in adults, they are in agreement with published observations of the effects of EHDP on calcium absorption in experimental animals.", "contents": "Calcium balance in children treated with diphosphonates. Serial mineral balances have been obtained in 3 children undergoing therapy with EHDP (ethane-1-hydroxy-1, 1-diphosphonate) for diseases involving ectopic calcification. Although clinical outcome was not uniformly satisfactory, all cases showed an overall reduction in calcium balance. This was due to increased faecal excretion of calcium and was most marked after a long duration of therapy. Although these results conflict with reported experience in adults, they are in agreement with published observations of the effects of EHDP on calcium absorption in experimental animals."} {"id": "PMID:167665", "title": "Psoriatic therapeutics and glucose-6-phosphate dehydrogenase.", "content": "The inhibitory effects of various agents on the enzyme glucose-6-phosphate dehydrogenase have been studied in vitro. Stress is laid on the calculation of kinetic parameters such as true K-I values. The most active inhibitor was methotrexate, closely followed by cGMP. The increase in inhibitory activity after incubation of methotrexate with liver slices is discussed.", "contents": "Psoriatic therapeutics and glucose-6-phosphate dehydrogenase. The inhibitory effects of various agents on the enzyme glucose-6-phosphate dehydrogenase have been studied in vitro. Stress is laid on the calculation of kinetic parameters such as true K-I values. The most active inhibitor was methotrexate, closely followed by cGMP. The increase in inhibitory activity after incubation of methotrexate with liver slices is discussed."} {"id": "PMID:167666", "title": "Wound infection during the Yom Kippur war: observations concerning antibiotic prophylaxis and therapy.", "content": "Eighty-eight episodes of wound associated infection were identified among 624 consecutively admitted battlefield casualties. Ninety-one per cent of infections occurred during the administration of antibiotic therapy or prophylaxis and 65% were associated with the use of multiple antibacterial agents. Gram negative bacillary and mixed microbial infection predominated and were found to increase in relative incidence after the second day of hospitalization. Appropriate therapy, based on disc sensitivity testing, was administered in only 33% of infectious episodes. The practice of antibiotic wound prophylaxis may contribute to the incidence and nature of infection in battlefield wounds. Problems unique to the handling of battlefield wounded are discussed in comparing the present data with those of other war associated and civilian studies.", "contents": "Wound infection during the Yom Kippur war: observations concerning antibiotic prophylaxis and therapy. Eighty-eight episodes of wound associated infection were identified among 624 consecutively admitted battlefield casualties. Ninety-one per cent of infections occurred during the administration of antibiotic therapy or prophylaxis and 65% were associated with the use of multiple antibacterial agents. Gram negative bacillary and mixed microbial infection predominated and were found to increase in relative incidence after the second day of hospitalization. Appropriate therapy, based on disc sensitivity testing, was administered in only 33% of infectious episodes. The practice of antibiotic wound prophylaxis may contribute to the incidence and nature of infection in battlefield wounds. Problems unique to the handling of battlefield wounded are discussed in comparing the present data with those of other war associated and civilian studies."} {"id": "PMID:167667", "title": "Flavoxate, a potent phosphodiesterase inhibitor.", "content": "The c-AMP phosphodiesterase inhibiting properties of flavoxate and of its main metabolite i.e. 3-methylflavone-8-carboxylic acid (MFCA), were assayed in vitro and compared to those of theophylline. Flavoxate and MFCA are competitive phosphodiesterase inhibitors, and are 21 and respectively 5 times more potent than theophylline. The smooth muscle relaxing activity of flavoxate possibly relies on this enzymatic mechanism.", "contents": "Flavoxate, a potent phosphodiesterase inhibitor. The c-AMP phosphodiesterase inhibiting properties of flavoxate and of its main metabolite i.e. 3-methylflavone-8-carboxylic acid (MFCA), were assayed in vitro and compared to those of theophylline. Flavoxate and MFCA are competitive phosphodiesterase inhibitors, and are 21 and respectively 5 times more potent than theophylline. The smooth muscle relaxing activity of flavoxate possibly relies on this enzymatic mechanism."} {"id": "PMID:167668", "title": "High synovial fluid white blood cell counts in pseudogout; Possible confusion with septic arthritis.", "content": "During a 12-month period, we have treated five patients with acute inflammatory arthritis and synovial fluid leukocyte counts of 65,000 to 100,00/cu mm with 93% to 100% polymorphonuclear cells, calcium pyrophosphate dihydrate crystals in the synovial fluid, and negative cultures. Four of these five were origingally treated for septic joints. We would like to emphasize this relatively uncommon, but important manifestation of pseudogout.", "contents": "High synovial fluid white blood cell counts in pseudogout; Possible confusion with septic arthritis. During a 12-month period, we have treated five patients with acute inflammatory arthritis and synovial fluid leukocyte counts of 65,000 to 100,00/cu mm with 93% to 100% polymorphonuclear cells, calcium pyrophosphate dihydrate crystals in the synovial fluid, and negative cultures. Four of these five were origingally treated for septic joints. We would like to emphasize this relatively uncommon, but important manifestation of pseudogout."} {"id": "PMID:167670", "title": "Changes in phosphatase activity associated with cell wall defects in Chlamydomonas reinhardi.", "content": "Experiments were performed to isolate mutants lacking alkaline phosphatase in Chlamydomonas reinhardi. Mutants with null enzyme activity were obtained. A cytological study of these mutants however revealed cell wall defects, suggesting that the loss of phosphatase activity in these strains is not due to the inactivation of the corresponding phosphatase structural gene but rather to the leakage of this enzyme as a consequence of the cell wall abnormality. Incidentally, this finding provides the basis of a convenient method for selecting easily cell wall mutants of Chlamydomonas.", "contents": "Changes in phosphatase activity associated with cell wall defects in Chlamydomonas reinhardi. Experiments were performed to isolate mutants lacking alkaline phosphatase in Chlamydomonas reinhardi. Mutants with null enzyme activity were obtained. A cytological study of these mutants however revealed cell wall defects, suggesting that the loss of phosphatase activity in these strains is not due to the inactivation of the corresponding phosphatase structural gene but rather to the leakage of this enzyme as a consequence of the cell wall abnormality. Incidentally, this finding provides the basis of a convenient method for selecting easily cell wall mutants of Chlamydomonas."} {"id": "PMID:167671", "title": "On the structure of the peptidoglycan of cell walls from Myxobacter AL-1 (myxobacterales).", "content": "Basically the peptidoglycan of Myxobater AL-1 consists of alternating beta-1,4-linked N-acetylglucosamic-N-acetylmuramic acid chains. After splitting the aminosugar backbone with a specific algal enzyme three subunits arise: a monomer, a dimer and a timer. Investigation of the monomer with specific enzymes and comparison of the degradation products to standards derived from other bacterial peptidoglycans suggest the following structure of the monomer peptide: L-alanyl-D-glutamic-L-meso-diaminopimelic-D-alanine. A D-alanyl-D-meso-diaminopimelic acid bond is the bridgebond between the peptides of the subunits.", "contents": "On the structure of the peptidoglycan of cell walls from Myxobacter AL-1 (myxobacterales). Basically the peptidoglycan of Myxobater AL-1 consists of alternating beta-1,4-linked N-acetylglucosamic-N-acetylmuramic acid chains. After splitting the aminosugar backbone with a specific algal enzyme three subunits arise: a monomer, a dimer and a timer. Investigation of the monomer with specific enzymes and comparison of the degradation products to standards derived from other bacterial peptidoglycans suggest the following structure of the monomer peptide: L-alanyl-D-glutamic-L-meso-diaminopimelic-D-alanine. A D-alanyl-D-meso-diaminopimelic acid bond is the bridgebond between the peptides of the subunits."} {"id": "PMID:167672", "title": "The effect of soluble antigens from polyoma tumor and liver cells on stimulation of lymph nodes measured by incorporation of 14C-leucine.", "content": "The effect of solube antigens from polyoma tumor cells, liver antigens and PHA on lymph node cells from tumor bearers and on normal lymph node cells in CBA mice was studied. The stimulation index was calculated on the basis of incorporation of 14C-leucine in short-term cultures. The stimulation index was lower in lymphocytes derived from tumor bearers than those from normal donors. The blastoid responses to polyoma-associated antigens and PHA were similar, in contrast to liver-associated antigens. It was concluded that stimulation of liver antigens may be connected with different chemical structure, mainly of carbohydrate components.", "contents": "The effect of soluble antigens from polyoma tumor and liver cells on stimulation of lymph nodes measured by incorporation of 14C-leucine. The effect of solube antigens from polyoma tumor cells, liver antigens and PHA on lymph node cells from tumor bearers and on normal lymph node cells in CBA mice was studied. The stimulation index was calculated on the basis of incorporation of 14C-leucine in short-term cultures. The stimulation index was lower in lymphocytes derived from tumor bearers than those from normal donors. The blastoid responses to polyoma-associated antigens and PHA were similar, in contrast to liver-associated antigens. It was concluded that stimulation of liver antigens may be connected with different chemical structure, mainly of carbohydrate components."} {"id": "PMID:167673", "title": "Training examiners to administer a quantitative neurological examination for a multicenter clinical trial.", "content": "A battery of quantitative neurological tests was used in a multicenter clinical trial to compare ACTH with placebo for the treatment of patients with multiple sclerosis in acute exacerbation. Since the battery of tests was administered in ten centers by physical therapists, it was critical that the examiners were well trained and remained so. Results of experiments showed that physical therapists could be successfully trained to administer the tests in a uniform fashion and remained trained for three years, the duration of the clinical trial. The fact that physical therapists are not taught tell-tale side effects of a treatment, and hence do not perceive these as do the physician examiners, introduces another level of objectivity into neurological clinical trials.", "contents": "Training examiners to administer a quantitative neurological examination for a multicenter clinical trial. A battery of quantitative neurological tests was used in a multicenter clinical trial to compare ACTH with placebo for the treatment of patients with multiple sclerosis in acute exacerbation. Since the battery of tests was administered in ten centers by physical therapists, it was critical that the examiners were well trained and remained so. Results of experiments showed that physical therapists could be successfully trained to administer the tests in a uniform fashion and remained trained for three years, the duration of the clinical trial. The fact that physical therapists are not taught tell-tale side effects of a treatment, and hence do not perceive these as do the physician examiners, introduces another level of objectivity into neurological clinical trials."} {"id": "PMID:167677", "title": "Rhinovirus type 14 RNA polymerase complexes.", "content": "Rhinovirus type 14 RNA-dependent RNA polymerase complexes were isolated from microsomal and soluble fraction of infected KB cells. Maximum activities were measured at at 6 and 7 hours post inoculation (p.i.) for microsomal and soluble polymerases, respectively. Both polymerase activities are considerably reduced by 8 to 9 hours, p.i., and interval in which the in vivo rate of synthesis of viral RNA is maximal. In vitro RNA products of RNA polymerases in both fractions consist of ribonuclease-sensitive and ribonuclease-resistant RNA of heterogeneous sizes. Detergent treatment of the microsomal RNA polymerase(s) did not affect the total amount of RNA synthesized, the proportion of ribonuclease-sensitive RNA synthesized or the size of the RNA products. The data suggest that RV14RNA polymerase complexes are intially associated with membranes but are then irreversibly released into the soluble phase of the cytoplasm; possible explanations for this phenomena are discussed.", "contents": "Rhinovirus type 14 RNA polymerase complexes. Rhinovirus type 14 RNA-dependent RNA polymerase complexes were isolated from microsomal and soluble fraction of infected KB cells. Maximum activities were measured at at 6 and 7 hours post inoculation (p.i.) for microsomal and soluble polymerases, respectively. Both polymerase activities are considerably reduced by 8 to 9 hours, p.i., and interval in which the in vivo rate of synthesis of viral RNA is maximal. In vitro RNA products of RNA polymerases in both fractions consist of ribonuclease-sensitive and ribonuclease-resistant RNA of heterogeneous sizes. Detergent treatment of the microsomal RNA polymerase(s) did not affect the total amount of RNA synthesized, the proportion of ribonuclease-sensitive RNA synthesized or the size of the RNA products. The data suggest that RV14RNA polymerase complexes are intially associated with membranes but are then irreversibly released into the soluble phase of the cytoplasm; possible explanations for this phenomena are discussed."} {"id": "PMID:167678", "title": "Evidence of chronic persistent infections with polyomaviruses (BK type) in renal transplant recipients.", "content": "Ten renal transplant recipients showing a significant increase in human polyomavirus antibodies, indicative of an acute infection, were followed up serologically over periods ranging from two months to more than two years. Fifty-four serum specimens were available for the study and they were tested by both haemagglutination-inhibition and complement-fixation. Polyomavirus antigens were prepared from the BK and SV40-like strains of polyomaviruses, and from the SV40 virus. One strain of polyomavirus, related to the BK strain was isolated from the urine of one of these patients. Two other BK strains were recovered from the urine and kidney, respectively, of transplant recipients not included in this study. Sera of these two patients were not obtained until the transplantation was made; they were already highly positive for polyomavirus antibodies, precluding the demonstration of an increase in antibody titer. Serologic results have shown that HAI antibodies persist at high titers throughout the observation period. This persistence ranged from two to four months (four cases), seven to eleven months (three cases) and thirteen to twenty months (three cases). In none of the cases could a decrease of high titer be demonstrated. Moreover, density gradient studies have shown that specific IgM antibodies also tend to persist over many months. Similar serologic results were obtained in complement-fixation tests with a BK antigen. Titers were at least 1 in 30 in the study group, but were not observed among healthy blood donors. All sera were uniformly negative for SV40 and SV40-like antigens. One polyomavirus isolation was successful from urine obtained six months after initial serologic evidence for a polyomavirus infection. The other two viruses were isolated from materials taken four and seven months after first detection of polyomavirus antibodies at high titer. Both serologic evidence and viral isolations seem to indicate that polyomaviruses (BK type) might cause a chronic infection in humans.", "contents": "Evidence of chronic persistent infections with polyomaviruses (BK type) in renal transplant recipients. Ten renal transplant recipients showing a significant increase in human polyomavirus antibodies, indicative of an acute infection, were followed up serologically over periods ranging from two months to more than two years. Fifty-four serum specimens were available for the study and they were tested by both haemagglutination-inhibition and complement-fixation. Polyomavirus antigens were prepared from the BK and SV40-like strains of polyomaviruses, and from the SV40 virus. One strain of polyomavirus, related to the BK strain was isolated from the urine of one of these patients. Two other BK strains were recovered from the urine and kidney, respectively, of transplant recipients not included in this study. Sera of these two patients were not obtained until the transplantation was made; they were already highly positive for polyomavirus antibodies, precluding the demonstration of an increase in antibody titer. Serologic results have shown that HAI antibodies persist at high titers throughout the observation period. This persistence ranged from two to four months (four cases), seven to eleven months (three cases) and thirteen to twenty months (three cases). In none of the cases could a decrease of high titer be demonstrated. Moreover, density gradient studies have shown that specific IgM antibodies also tend to persist over many months. Similar serologic results were obtained in complement-fixation tests with a BK antigen. Titers were at least 1 in 30 in the study group, but were not observed among healthy blood donors. All sera were uniformly negative for SV40 and SV40-like antigens. One polyomavirus isolation was successful from urine obtained six months after initial serologic evidence for a polyomavirus infection. The other two viruses were isolated from materials taken four and seven months after first detection of polyomavirus antibodies at high titer. Both serologic evidence and viral isolations seem to indicate that polyomaviruses (BK type) might cause a chronic infection in humans."} {"id": "PMID:167679", "title": "Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production.", "content": "Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.", "contents": "Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production. Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines."} {"id": "PMID:167680", "title": "The enhancing effect of copper, nickel, and cobalt ions on plaque formation by Semliki Forest virus (SFV) in chicken embryo fibroblasts.", "content": "In cultured chicken embryo fibroblasts treated with copper-(copper cation 10-minus 3.5-10-minus 5 M), nickel and cobalt salts an enhancement of the plating efficiency of Semliki Forest virus could be observed. This augmented plaque formation was most probably due to a higher adsorption rate of virions to the cell surface under the influence of the transition metal ions. The plating efficiency of West Nile virus in chicken-embryo fibroblasts and, to a lesser degree, of poliovius type 1 and 2 in KB-cells was also enhanced by copper sulfate.", "contents": "The enhancing effect of copper, nickel, and cobalt ions on plaque formation by Semliki Forest virus (SFV) in chicken embryo fibroblasts. In cultured chicken embryo fibroblasts treated with copper-(copper cation 10-minus 3.5-10-minus 5 M), nickel and cobalt salts an enhancement of the plating efficiency of Semliki Forest virus could be observed. This augmented plaque formation was most probably due to a higher adsorption rate of virions to the cell surface under the influence of the transition metal ions. The plating efficiency of West Nile virus in chicken-embryo fibroblasts and, to a lesser degree, of poliovius type 1 and 2 in KB-cells was also enhanced by copper sulfate."} {"id": "PMID:167681", "title": "Virulence of temperature-sensitive mutants of foot-and-mouth disease virus.", "content": "A number of temperature-sensitive mutants isolated from two strains of foot-and-mouth disease virus were examined for their virulence in suckling mice. The majority of the mutants were found to be less virulent than the parent virus strains, ranging from slight to total attenuation, but two mutants retained parental levels of virulence. There was no correlation between mutant cut-off temperatures and virulence, or the revertant content of mutant preparations and virulence. It was not always possible to regain parental levels of virulence by isolating phenotypic revertants or wild-type recombinants from genetic crosses, but recombinants were significantly more virulent than either of the two input viruses in a genetic cross.", "contents": "Virulence of temperature-sensitive mutants of foot-and-mouth disease virus. A number of temperature-sensitive mutants isolated from two strains of foot-and-mouth disease virus were examined for their virulence in suckling mice. The majority of the mutants were found to be less virulent than the parent virus strains, ranging from slight to total attenuation, but two mutants retained parental levels of virulence. There was no correlation between mutant cut-off temperatures and virulence, or the revertant content of mutant preparations and virulence. It was not always possible to regain parental levels of virulence by isolating phenotypic revertants or wild-type recombinants from genetic crosses, but recombinants were significantly more virulent than either of the two input viruses in a genetic cross."} {"id": "PMID:167684", "title": "A bovine adenovirus type 3: isolation, characterization, and experimental infection in calves.", "content": "A virus was isolated from a group of feedlot cattle with acute respiratory disease that was characterized by physicochemical methods as an adenovirus and identified serologically as a bovine adenovirus type 3. Intratracheal inoculation of three 4 month old colostrum deprived calves resulted in pyrexia, hyperpnea, dyspnea, anorexia and in one animal a mild diarrhea.", "contents": "A bovine adenovirus type 3: isolation, characterization, and experimental infection in calves. A virus was isolated from a group of feedlot cattle with acute respiratory disease that was characterized by physicochemical methods as an adenovirus and identified serologically as a bovine adenovirus type 3. Intratracheal inoculation of three 4 month old colostrum deprived calves resulted in pyrexia, hyperpnea, dyspnea, anorexia and in one animal a mild diarrhea."} {"id": "PMID:167683", "title": "Experimental studies concerning the possibility of a latent carrier state in bovine herpes mammillitis (BHM).", "content": "Adult bovines, young calves and young rats were infected with bovine herpes mammillitis (BHM) virus providing a group of BHM-recovered animals in which to investigate a possible latent carrier state. The progression of the acute infection and serological response was essentially similar to that previously reported. The effect of natural (calving, littering) and artificial (corticosteroid treatment) stress on these animals following recovery from infection was investigated, but reactivation of BHM was never detected. Long term observation of cocultures of BHM virus infected-and-recovered bovine teat dermis with bovine embryo cells failed to reveal any evidence for the induction of BHM virus replication even in those cocultures treated with mitomycin C or bromodeoxyuridine. Similarly, cocultures utilizing lumbar dorsal root ganglia from the same animals were also negative with respect to the induction of virus replication. Experiments using cytosine arabinoside indicated that an artificial in vitro latent carrier state of BHM virus could be maintained for 6 days with subsequent sporadic virus reactivation, but an attempt to maintain such a state for 12 days was unsuccessful, with no subsequent virus reactivation.", "contents": "Experimental studies concerning the possibility of a latent carrier state in bovine herpes mammillitis (BHM). Adult bovines, young calves and young rats were infected with bovine herpes mammillitis (BHM) virus providing a group of BHM-recovered animals in which to investigate a possible latent carrier state. The progression of the acute infection and serological response was essentially similar to that previously reported. The effect of natural (calving, littering) and artificial (corticosteroid treatment) stress on these animals following recovery from infection was investigated, but reactivation of BHM was never detected. Long term observation of cocultures of BHM virus infected-and-recovered bovine teat dermis with bovine embryo cells failed to reveal any evidence for the induction of BHM virus replication even in those cocultures treated with mitomycin C or bromodeoxyuridine. Similarly, cocultures utilizing lumbar dorsal root ganglia from the same animals were also negative with respect to the induction of virus replication. Experiments using cytosine arabinoside indicated that an artificial in vitro latent carrier state of BHM virus could be maintained for 6 days with subsequent sporadic virus reactivation, but an attempt to maintain such a state for 12 days was unsuccessful, with no subsequent virus reactivation."} {"id": "PMID:167685", "title": "Human and primate poxviruses: I. Growth characteristics of cytolytic and tumor variants.", "content": "The dual potential of poxviruses to be cytolytic and tumorgenic has been extended. Yaba monkey tumor virus formed foci on monkey and human embryonic cells. Cytolytic or plaque-forming virus was isolated from Yaba tumor homogenates by selective sucrose centrifugation and passage through monkey or human embryonic cells. Monkey pox virus (MPV) was cytolytic for monkey cells or human embryonic cells, but upon passage onto young monolayers of human carcinoma cells, HeLa, produced a restricted cytopathic effect on first transfer, foci on second transfer and cytolysis after the fourth transfer. If HeLa monolayers were compact, the rapid growth precluded overt expression of cytolytic MPV. Electron micrographs of cytolytic Yaba indicated that Yaba development was similar to vaccinia and MPV but not totally organized. Growth curves of vaccinia, MPV and cytolytic Yaba were essentially identical in monkey and human embryonic cell lines.", "contents": "Human and primate poxviruses: I. Growth characteristics of cytolytic and tumor variants. The dual potential of poxviruses to be cytolytic and tumorgenic has been extended. Yaba monkey tumor virus formed foci on monkey and human embryonic cells. Cytolytic or plaque-forming virus was isolated from Yaba tumor homogenates by selective sucrose centrifugation and passage through monkey or human embryonic cells. Monkey pox virus (MPV) was cytolytic for monkey cells or human embryonic cells, but upon passage onto young monolayers of human carcinoma cells, HeLa, produced a restricted cytopathic effect on first transfer, foci on second transfer and cytolysis after the fourth transfer. If HeLa monolayers were compact, the rapid growth precluded overt expression of cytolytic MPV. Electron micrographs of cytolytic Yaba indicated that Yaba development was similar to vaccinia and MPV but not totally organized. Growth curves of vaccinia, MPV and cytolytic Yaba were essentially identical in monkey and human embryonic cell lines."} {"id": "PMID:167686", "title": "Exacerbation and reactivation of Herpesvirus hominis infection in mice by cyclophosphamide.", "content": "Cyclophosphamide has been shown to potentiate the growth of Herpesvirus hominis in the skin of Webster Schneider mice. Higher skin yields of virus were obtained, marked dissemination of virus to the brain was produced and mortality in mice was increased. Serum neutralizing antibody titres were suppressed. The system may serve as a good model for the study of specific antiherpes drugs.", "contents": "Exacerbation and reactivation of Herpesvirus hominis infection in mice by cyclophosphamide. Cyclophosphamide has been shown to potentiate the growth of Herpesvirus hominis in the skin of Webster Schneider mice. Higher skin yields of virus were obtained, marked dissemination of virus to the brain was produced and mortality in mice was increased. Serum neutralizing antibody titres were suppressed. The system may serve as a good model for the study of specific antiherpes drugs."} {"id": "PMID:167687", "title": "Studies of Marek's disease herpesvirus and turkey herpesvirus specific common antigen which stimulates the production of neutralizing antibodies.", "content": "An agar-gel precipitation antigen prepared from the skin (feather-Ag) of chicken infected with JM strain of Marek's disease herpesvirus (MDHV) and cell extracts of cultures infected with either Type 2 plaque producing agent (PPA) of MDHV or turkey herpesvirus (HVT) (Type 2-Ag, HVT-Ag) had 1 precipitation line in common. Hyperimmune sera to the common antigen (common-Ag) neutralized to a greater extent by homologous antiserum. Absorption of HVT antiserum or hyperimmune serum to Type 2 PPA with common-Ag reduced their neutralizing activity. This reduction was almost complete with homologous antigen but less complete with heterologous antigen. The location of antigen in Type 2 PPA and HVT infected cells was determined using hyperimmune serum to the common-Ag in fluorescent antibody tests. Antigen mainly occurred in the cytoplasm of cells corresponding to the rounded refractile cells in the plaques, whereas unfixed cells showed antigen on the cytoplasmic membrane. The common-Ag associated with MDHV or HVT infections might be a virus structural component which is associated with the envelope.", "contents": "Studies of Marek's disease herpesvirus and turkey herpesvirus specific common antigen which stimulates the production of neutralizing antibodies. An agar-gel precipitation antigen prepared from the skin (feather-Ag) of chicken infected with JM strain of Marek's disease herpesvirus (MDHV) and cell extracts of cultures infected with either Type 2 plaque producing agent (PPA) of MDHV or turkey herpesvirus (HVT) (Type 2-Ag, HVT-Ag) had 1 precipitation line in common. Hyperimmune sera to the common antigen (common-Ag) neutralized to a greater extent by homologous antiserum. Absorption of HVT antiserum or hyperimmune serum to Type 2 PPA with common-Ag reduced their neutralizing activity. This reduction was almost complete with homologous antigen but less complete with heterologous antigen. The location of antigen in Type 2 PPA and HVT infected cells was determined using hyperimmune serum to the common-Ag in fluorescent antibody tests. Antigen mainly occurred in the cytoplasm of cells corresponding to the rounded refractile cells in the plaques, whereas unfixed cells showed antigen on the cytoplasmic membrane. The common-Ag associated with MDHV or HVT infections might be a virus structural component which is associated with the envelope."} {"id": "PMID:167689", "title": "Sporadic bovine meningo-encephalitis-isolation of a paramyxovirus.", "content": "Isolation of a viral agent (107) directly from brain explants of a 15-month-old heifer with symptoms of a sporadic encephalomyelitis is described. The virus shares properties with the paramyxovirus family. It grows in a variety of cell cultures from different species, and induces nuclear and cytoplasmic inclusion bodies in infected cells. Nucleocapsids measuring 17 nm in diameter were found in the nucleus and cytoplasm of these cells when studied electron microscopically, thus indicating a close relationship of the agent to the measles-distemper-rinderpest group. No infectious virus was released from infected cells, although alignment of nucleocapsids was observed beneath the cell membrane, and no hemagglutinating activity could be detected with the methods employed. The 107 agent was compared serologically with parainfluenza viruses type 1, 2 and 3, simian virus 5, mumps and Newcastle disease virus (NDV), two bovine respiratory syncytial viruses and measles/subacute sclerosing panencephalitis, distemper and rinderpest viruses, always using 107 virus infected CV1 cells and antiserum of the different viruses in indirect FA tests. Positive FA reactions were observed only with two sera obtained from SSPE patients with high antibody titer to SSPE virus, and with one rabbit-anti-rinderpest serum. The titers of these sera to 107 virus, however, were significantly lower than those against homologous viruses. Five out of 9 sera from randomly selected healthy cattle showed antibody titers between 1:10 and 1:80 to 107 virus in FA tests. The significance of these results is discussed with respect to the epidemiology of SSPE in children and its possible implication with rinderpest in Europe.", "contents": "Sporadic bovine meningo-encephalitis-isolation of a paramyxovirus. Isolation of a viral agent (107) directly from brain explants of a 15-month-old heifer with symptoms of a sporadic encephalomyelitis is described. The virus shares properties with the paramyxovirus family. It grows in a variety of cell cultures from different species, and induces nuclear and cytoplasmic inclusion bodies in infected cells. Nucleocapsids measuring 17 nm in diameter were found in the nucleus and cytoplasm of these cells when studied electron microscopically, thus indicating a close relationship of the agent to the measles-distemper-rinderpest group. No infectious virus was released from infected cells, although alignment of nucleocapsids was observed beneath the cell membrane, and no hemagglutinating activity could be detected with the methods employed. The 107 agent was compared serologically with parainfluenza viruses type 1, 2 and 3, simian virus 5, mumps and Newcastle disease virus (NDV), two bovine respiratory syncytial viruses and measles/subacute sclerosing panencephalitis, distemper and rinderpest viruses, always using 107 virus infected CV1 cells and antiserum of the different viruses in indirect FA tests. Positive FA reactions were observed only with two sera obtained from SSPE patients with high antibody titer to SSPE virus, and with one rabbit-anti-rinderpest serum. The titers of these sera to 107 virus, however, were significantly lower than those against homologous viruses. Five out of 9 sera from randomly selected healthy cattle showed antibody titers between 1:10 and 1:80 to 107 virus in FA tests. The significance of these results is discussed with respect to the epidemiology of SSPE in children and its possible implication with rinderpest in Europe."} {"id": "PMID:167690", "title": "The effect of arginine deprivation on the cytopathogenic effect and replication of human cytomegalovirus.", "content": "Arginine is necessary for the development of the cytopathogenic effect of human cytomegalovirus in human embryonic fibroblasts. It is also required, though in greater concentrations, for the production of infective virions, the requirement being at an early stage of replication. Inhibitor studies suggested that this block in replication caused by arginine deficiency was prior to the formation of viral DNA. Withdrawal of arginine from the medium 24 or 48 hours after infection resulted in a decline in virus production indicating that the continued presence of the amino acid is necessary for constant virus production. Infected cultures deprived of arginine could be stimulated to produce cytopathic effects and infective virions by replacement of the amino acid even eight days after inoculation, demonstrating that the information for cytomegalovirus replication remains intact within the cell. This establishment of latency in vitro may be related to the ability of the virus to establish a similar state in vivo.", "contents": "The effect of arginine deprivation on the cytopathogenic effect and replication of human cytomegalovirus. Arginine is necessary for the development of the cytopathogenic effect of human cytomegalovirus in human embryonic fibroblasts. It is also required, though in greater concentrations, for the production of infective virions, the requirement being at an early stage of replication. Inhibitor studies suggested that this block in replication caused by arginine deficiency was prior to the formation of viral DNA. Withdrawal of arginine from the medium 24 or 48 hours after infection resulted in a decline in virus production indicating that the continued presence of the amino acid is necessary for constant virus production. Infected cultures deprived of arginine could be stimulated to produce cytopathic effects and infective virions by replacement of the amino acid even eight days after inoculation, demonstrating that the information for cytomegalovirus replication remains intact within the cell. This establishment of latency in vitro may be related to the ability of the virus to establish a similar state in vivo."} {"id": "PMID:167691", "title": "Early cytoplasmic vacuolization of African green monkey kidney cells by SV40.", "content": "As early as 3--4 hours after infection with SV40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10--20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by preincubating the virus with specific antiserum, or by heating the virus with MgCl2. The ECV could be induced by UV-irradiated SV40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV40 virion and the vacuolization is not associated with the replication of SV40.", "contents": "Early cytoplasmic vacuolization of African green monkey kidney cells by SV40. As early as 3--4 hours after infection with SV40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10--20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by preincubating the virus with specific antiserum, or by heating the virus with MgCl2. The ECV could be induced by UV-irradiated SV40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV40 virion and the vacuolization is not associated with the replication of SV40."} {"id": "PMID:167692", "title": "Identification of strains of herpes simplex virus by comparison of the density of their DNA using the preparative ultracentrifuge.", "content": "The buoyant densities of the DNA of herpes simplex virus type 1, type 2 and Pseudorabies virus, as determined in the analytical ultracentrifuge, are 1.725, 1.727 and 1.731 correlating with G+C contents of 67, 69 and 73 per cent respectively. The density differences for the DNA's of type 1 and type 2 herpes simplex viruses have been confirmed in experiments with isotopically labelled DNA from four type 1 and six type 2 strains by preparative CsCl gradient ultracentrifugation. The DNA of all the type 2 strains was denser than that of any of the type 1 strains examined. Despite these differences in DNA base composition of type 1 and type 2 strains, nearest neighbour analysis of their DNA's disclosed no obvious differences in doublet pattern or general design.", "contents": "Identification of strains of herpes simplex virus by comparison of the density of their DNA using the preparative ultracentrifuge. The buoyant densities of the DNA of herpes simplex virus type 1, type 2 and Pseudorabies virus, as determined in the analytical ultracentrifuge, are 1.725, 1.727 and 1.731 correlating with G+C contents of 67, 69 and 73 per cent respectively. The density differences for the DNA's of type 1 and type 2 herpes simplex viruses have been confirmed in experiments with isotopically labelled DNA from four type 1 and six type 2 strains by preparative CsCl gradient ultracentrifugation. The DNA of all the type 2 strains was denser than that of any of the type 1 strains examined. Despite these differences in DNA base composition of type 1 and type 2 strains, nearest neighbour analysis of their DNA's disclosed no obvious differences in doublet pattern or general design."} {"id": "PMID:167695", "title": "[Microadenomas and hypersecreting pituitary adenomas].", "content": "The early radiographic changes of the sella turcica in the cases of hypersecreting pituitary adenomas (Cushing disease, acromegaly, amenorrhea-galactorrhea) are reported and discussed. The finding of the double contour of the sellar floor and the small crescentic bulging of its antero-inferior wall, with the aid of the tomographic cuts of the sella, has permited the diagnosis of the microadenoma'a localization. With this it si possible the achievement of a selective excision of the lesion in the initial stage, when the tumor has not caused yet irreversible damage to the inside normal pituitary tissue. This surgery is performed in the precocious stage with the primary goal to preserve the normal gland, without hurt it to avoid postoperative hipopituitarism. A anatomo-radiologic classification of the alterations sella turcica in 4 grades is made, which is of great utility for the surgical prognostic, since we have observed clinical and biological cure over 90% in the grade 1, 75% in the grade 2, 50% in the grade 3 and up to 10% in the grade 4 in the first surgery.", "contents": "[Microadenomas and hypersecreting pituitary adenomas]. The early radiographic changes of the sella turcica in the cases of hypersecreting pituitary adenomas (Cushing disease, acromegaly, amenorrhea-galactorrhea) are reported and discussed. The finding of the double contour of the sellar floor and the small crescentic bulging of its antero-inferior wall, with the aid of the tomographic cuts of the sella, has permited the diagnosis of the microadenoma'a localization. With this it si possible the achievement of a selective excision of the lesion in the initial stage, when the tumor has not caused yet irreversible damage to the inside normal pituitary tissue. This surgery is performed in the precocious stage with the primary goal to preserve the normal gland, without hurt it to avoid postoperative hipopituitarism. A anatomo-radiologic classification of the alterations sella turcica in 4 grades is made, which is of great utility for the surgical prognostic, since we have observed clinical and biological cure over 90% in the grade 1, 75% in the grade 2, 50% in the grade 3 and up to 10% in the grade 4 in the first surgery."} {"id": "PMID:167696", "title": "[The cell-independent influence on calcification in living bone and in vitro (author's transl)].", "content": "While there is no doubt that collagen is an important extra-cellular factor in the calcification of bone tissues, the exact nature of the process remains unclear. It has been explained in turn by the nucleation effect of corresponding lattice distances of apatite and collagen, that is, an oriented crystal overgrowth of the two substances which decreases the energy of nucleus formation, or by conformity between fibril-bundles and calciumphosphate crystal, or by the binding of phosphate to anionic positions of the collagen, as well as by the bone-forming effect of a non-collagen protein which is, however, separable from collagen. Because of their high viscosity proteo-polysaccharides inhibit crystal formation. Alkaline soluble proteo-pholysaccharides, however, appear to promote calcification in vitro and also in tissue of living bone. Lathyrogene and penicillamine impair the cross-linking in the bone collagen; this probably explains their disturbing effect on ossification. Diphosphonates would, like anorganic pyrophosphate, inhibit both the formation and dissolution of apatite crystal. Our research shows, however, that methanie-bis-phosphonate clearly promotes calcification, in vitro and in vivo. In vitro, and probably also in vivo, magnesium inhibits the formation of apatite crystal nucleus. Our research indicates moreover that magnesium also slows down the reduction of calcified bone tissue on account of its inhibiting effect on parathormone emission.", "contents": "[The cell-independent influence on calcification in living bone and in vitro (author's transl)]. While there is no doubt that collagen is an important extra-cellular factor in the calcification of bone tissues, the exact nature of the process remains unclear. It has been explained in turn by the nucleation effect of corresponding lattice distances of apatite and collagen, that is, an oriented crystal overgrowth of the two substances which decreases the energy of nucleus formation, or by conformity between fibril-bundles and calciumphosphate crystal, or by the binding of phosphate to anionic positions of the collagen, as well as by the bone-forming effect of a non-collagen protein which is, however, separable from collagen. Because of their high viscosity proteo-polysaccharides inhibit crystal formation. Alkaline soluble proteo-pholysaccharides, however, appear to promote calcification in vitro and also in tissue of living bone. Lathyrogene and penicillamine impair the cross-linking in the bone collagen; this probably explains their disturbing effect on ossification. Diphosphonates would, like anorganic pyrophosphate, inhibit both the formation and dissolution of apatite crystal. Our research shows, however, that methanie-bis-phosphonate clearly promotes calcification, in vitro and in vivo. In vitro, and probably also in vivo, magnesium inhibits the formation of apatite crystal nucleus. Our research indicates moreover that magnesium also slows down the reduction of calcified bone tissue on account of its inhibiting effect on parathormone emission."} {"id": "PMID:167697", "title": "Effects of chlorpromazine and diazepam on neuronal activities of the lateral vestibular nucleus in cats.", "content": "The effects of chlorpromazine and diazepam on vestibular neuronal activity were studied in gallamine immobilized cats. Chlorpromazine depressed all the P, N1 and N2-waves of field potentials in the lateral vestibular nucleus evoked by electrical stimulation of the vestibular nerve. Diazepam also reduced the amplitude of postsynaptic components (N1 and N2-waves), while the presynaptic one (P-wave) was slightly increased. Chlorpromazine suppressed the spontaneous as well as the increased vestibular neuronal firing following stimulation of the vestibular nerve. Diazepam enhanced the increased vestibular neuronal firing excited by the nerve stimulation and had no effect on the spontaneous unitary discharges.", "contents": "Effects of chlorpromazine and diazepam on neuronal activities of the lateral vestibular nucleus in cats. The effects of chlorpromazine and diazepam on vestibular neuronal activity were studied in gallamine immobilized cats. Chlorpromazine depressed all the P, N1 and N2-waves of field potentials in the lateral vestibular nucleus evoked by electrical stimulation of the vestibular nerve. Diazepam also reduced the amplitude of postsynaptic components (N1 and N2-waves), while the presynaptic one (P-wave) was slightly increased. Chlorpromazine suppressed the spontaneous as well as the increased vestibular neuronal firing following stimulation of the vestibular nerve. Diazepam enhanced the increased vestibular neuronal firing excited by the nerve stimulation and had no effect on the spontaneous unitary discharges."} {"id": "PMID:167698", "title": "Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study.", "content": "Histologic, histochemical, and ultrastructural studies of a tuberous xanthoma from a patient with homozygous type II hyperlipoproteinemia showed that all of the lipid was within histiocytic foam cells; no lipid was identified in interstitial regions or in blood vessels. Primitive mesenchymal cells, elongated perivascular and fibroblast-like cells, and lysosome-filled macrophages also were present within the xanthoma, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich foam cells. Morphologically, the lipid was in four different forms: large droplets, which were the dominant form, and membrane-bound crystals, concentric lamellar bodies, and ceroid. The paucity of membrane-bound lipid forms, relative to the abundant free lipid droplets, indicated that lysosomal digestion was a minor metabolic pathway for the intracellular metabolism of lipid in the xanthoma. Thus, nonlysosomal lipid storage in foam cells is a characteristic tissue response to the underlying metabolic defect in type II hyperlipoproteinemia.", "contents": "Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study. Histologic, histochemical, and ultrastructural studies of a tuberous xanthoma from a patient with homozygous type II hyperlipoproteinemia showed that all of the lipid was within histiocytic foam cells; no lipid was identified in interstitial regions or in blood vessels. Primitive mesenchymal cells, elongated perivascular and fibroblast-like cells, and lysosome-filled macrophages also were present within the xanthoma, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich foam cells. Morphologically, the lipid was in four different forms: large droplets, which were the dominant form, and membrane-bound crystals, concentric lamellar bodies, and ceroid. The paucity of membrane-bound lipid forms, relative to the abundant free lipid droplets, indicated that lysosomal digestion was a minor metabolic pathway for the intracellular metabolism of lipid in the xanthoma. Thus, nonlysosomal lipid storage in foam cells is a characteristic tissue response to the underlying metabolic defect in type II hyperlipoproteinemia."} {"id": "PMID:167699", "title": "Human model for studying seed-soil factors in blood-borne metastasis.", "content": "The relationship between tumor \"seed\" and tissue \"soil\" in blood-borne metastasis is poorly understood. Therefore, an explanatory human model is proposed. It is based on the hypothesis that the spread of lung cancer cells to the adrenal vein provides in man not only a variable attribute, lung cancer seed, but also a constant attribute, adrenal venous soil, as in a scientific experiment. Out of 100 cases of lung cancer, four histologic types proved their invasive potentiality in 45 subjects by colonizing the adrenal parenchyma proper and yet differed appreciably in their ability to grow in the adrenal venous blood. Hence, in all probability, the systematic study of venous blood will help in the discovery of the potentialities and limitations of human blood in tumor metastasis.", "contents": "Human model for studying seed-soil factors in blood-borne metastasis. The relationship between tumor \"seed\" and tissue \"soil\" in blood-borne metastasis is poorly understood. Therefore, an explanatory human model is proposed. It is based on the hypothesis that the spread of lung cancer cells to the adrenal vein provides in man not only a variable attribute, lung cancer seed, but also a constant attribute, adrenal venous soil, as in a scientific experiment. Out of 100 cases of lung cancer, four histologic types proved their invasive potentiality in 45 subjects by colonizing the adrenal parenchyma proper and yet differed appreciably in their ability to grow in the adrenal venous blood. Hence, in all probability, the systematic study of venous blood will help in the discovery of the potentialities and limitations of human blood in tumor metastasis."} {"id": "PMID:167702", "title": "Fine structure and origin of amyloid deposits in pituitary adenoma.", "content": "A pituitary adenoma with amyloid deposits was studied by light and electron microscopy. The amyloid material was radially oriented, deposited in the extracellular space, and often intermingled with small vesicles. It was surrounded by histiocytes with deep cytoplasmic invaginations. The histiocytes contained large autophagic vacuoles in which amyloid was also present. These features are similar to other forms of amyloidosis and suggest a histiocytic origin of the amyloid.", "contents": "Fine structure and origin of amyloid deposits in pituitary adenoma. A pituitary adenoma with amyloid deposits was studied by light and electron microscopy. The amyloid material was radially oriented, deposited in the extracellular space, and often intermingled with small vesicles. It was surrounded by histiocytes with deep cytoplasmic invaginations. The histiocytes contained large autophagic vacuoles in which amyloid was also present. These features are similar to other forms of amyloidosis and suggest a histiocytic origin of the amyloid."} {"id": "PMID:167703", "title": "Spironolactone bodies in an adrenal adenoma.", "content": "Spironolactone bodies were observed in an adrenal cortical adenoma that was removed from a patient with primary hyperaldosteronism (Conn syndrome) treated preoperatively with spironolactone. The electron microscopical evaluation of this adrenal cortical adenoma shows origin of spironolactone bodies from whorls of endoplasmic reticulum in cells with the cytoplasmic features of those from the zona glomerulosa of the adrenal gland. There was no evidence that the bodies were derived from mitochondria, which confirms recent ultrastructural findings in patients treated with spironolactone. These bodies have been described in the adrenal cortex only in patients who have received spironolactone, and the pharmacologic specificity of the bodies strongly suggests a direct mode of action by spironolactone on aldosterone production by cells of the adrenal zona glomerulosa.", "contents": "Spironolactone bodies in an adrenal adenoma. Spironolactone bodies were observed in an adrenal cortical adenoma that was removed from a patient with primary hyperaldosteronism (Conn syndrome) treated preoperatively with spironolactone. The electron microscopical evaluation of this adrenal cortical adenoma shows origin of spironolactone bodies from whorls of endoplasmic reticulum in cells with the cytoplasmic features of those from the zona glomerulosa of the adrenal gland. There was no evidence that the bodies were derived from mitochondria, which confirms recent ultrastructural findings in patients treated with spironolactone. These bodies have been described in the adrenal cortex only in patients who have received spironolactone, and the pharmacologic specificity of the bodies strongly suggests a direct mode of action by spironolactone on aldosterone production by cells of the adrenal zona glomerulosa."} {"id": "PMID:167704", "title": "EMC virus and cultured human fetal pancreatic cells. Ultrastructural observations.", "content": "Tissue cultures of pancreatic acinar cells of seven human fetuses were infected with either the M or the E variant of the encephalomyocarditis (EMC) virus. Between the third and fifth days after infection, severe ultrastructural damage was noted. Margination, condensation, and fragmentation of the nuclear chromatin and the appearance of numerous cytoplasmic vesicles filled with finely granular material were the major changes observed. Viral particles were not identified. One hundred plaque-forming units (PFU) were sufficient to induce these alterations with the M variant while 10,000 PFU were needed to obtain the same results with the EMC-E virus. The described lesions are qualitatively similar to those induced in vivo in experimental CD-1 mice infected with the virus.", "contents": "EMC virus and cultured human fetal pancreatic cells. Ultrastructural observations. Tissue cultures of pancreatic acinar cells of seven human fetuses were infected with either the M or the E variant of the encephalomyocarditis (EMC) virus. Between the third and fifth days after infection, severe ultrastructural damage was noted. Margination, condensation, and fragmentation of the nuclear chromatin and the appearance of numerous cytoplasmic vesicles filled with finely granular material were the major changes observed. Viral particles were not identified. One hundred plaque-forming units (PFU) were sufficient to induce these alterations with the M variant while 10,000 PFU were needed to obtain the same results with the EMC-E virus. The described lesions are qualitatively similar to those induced in vivo in experimental CD-1 mice infected with the virus."} {"id": "PMID:167705", "title": "Thyroid peroxidase deficiency in Batten-Spielmeyer-Vogt disease.", "content": "Thyroid tissue from two patients with Batten-Spielmeyer-Vogt disease (BSV) was studied for peroxidase enzyme activity and for morphological abnormalities by light and electron microscopy. Diagnosis was confirmed by the demonstration of intracytoplasmic material identical to that described in other reported cases of BSV. There was a substantial decrease in peroxidase activity in the thyroid tissue from both patients. An abnormally low level of peroxidase activity had previously been demonstrated in the white blood cells of these patients. Thyroid biopsy offers obvious advantages over brain biopsy, provides adequate tissue for enzyme analysis, and allows the demonstration of the intracytoplasmic structures characteristic of BSV.", "contents": "Thyroid peroxidase deficiency in Batten-Spielmeyer-Vogt disease. Thyroid tissue from two patients with Batten-Spielmeyer-Vogt disease (BSV) was studied for peroxidase enzyme activity and for morphological abnormalities by light and electron microscopy. Diagnosis was confirmed by the demonstration of intracytoplasmic material identical to that described in other reported cases of BSV. There was a substantial decrease in peroxidase activity in the thyroid tissue from both patients. An abnormally low level of peroxidase activity had previously been demonstrated in the white blood cells of these patients. Thyroid biopsy offers obvious advantages over brain biopsy, provides adequate tissue for enzyme analysis, and allows the demonstration of the intracytoplasmic structures characteristic of BSV."} {"id": "PMID:167706", "title": "Characteristics of the sleep of men in simulated space flights.", "content": "A study of the sleep of men in simulated space flight has shown that, during different effects (diminished motor activity, noise, rotation), monotony and time of the exposure is the general pathogenetic factor producing sleep disturbances. The monotony factor was responsible for typical changes in sleep function (difficulty involved in falling asleep, disturbed continuity of sleep as a process, decline in the depth, etc.), whose degree was related not only to the professional importance of the experiment but also to the individual intolerance to the main exposure. In these cases, the action of somnogenic mechanisms developed against the background of the action of analyzers (vestibular, accoustic, proprioceptive) that were under load and whose excitation during hypokinesia, noise, and rotation, especially in poorly adapted people, led to cumulation and was expressed in the phenomenon of spontaneous awakening. In addition to that, the genesis of dyssomnia, particularly during bedrest and water immersion, included hemodynamic disturbances induced by blood redistribution due to the recumbent position and monotonous motor activity. The psychosomatic feelings (congestion, edema, irresistible desire to stand up and stretch) brought about emotional strain which was later enhanced by the duration of the exposure.", "contents": "Characteristics of the sleep of men in simulated space flights. A study of the sleep of men in simulated space flight has shown that, during different effects (diminished motor activity, noise, rotation), monotony and time of the exposure is the general pathogenetic factor producing sleep disturbances. The monotony factor was responsible for typical changes in sleep function (difficulty involved in falling asleep, disturbed continuity of sleep as a process, decline in the depth, etc.), whose degree was related not only to the professional importance of the experiment but also to the individual intolerance to the main exposure. In these cases, the action of somnogenic mechanisms developed against the background of the action of analyzers (vestibular, accoustic, proprioceptive) that were under load and whose excitation during hypokinesia, noise, and rotation, especially in poorly adapted people, led to cumulation and was expressed in the phenomenon of spontaneous awakening. In addition to that, the genesis of dyssomnia, particularly during bedrest and water immersion, included hemodynamic disturbances induced by blood redistribution due to the recumbent position and monotonous motor activity. The psychosomatic feelings (congestion, edema, irresistible desire to stand up and stretch) brought about emotional strain which was later enhanced by the duration of the exposure."} {"id": "PMID:167707", "title": "Development of a live attenuated varicella vaccine.", "content": "The Oka strain of varicella virus, isolated in our labolatory, was serially cultivated in guinea-pig embryo cultures (GPEC), and a considerable amount of cell-free virus was obtained from infected cell. GPEC passage virus at the 6th passage level was used in a small scale field trial. Susceptible children of 1 to 10 years old were injected subcutaneously with 100 to 1,000 PFU of virus. No clinical reactions due to the vaccination were observed in any children, and a high rate of antibody response was obtained with viral doses of more than 200 PFU. Attenuated virus obtained by passage in GPEC was propagated in human diploid (WI-38) cells, and it was also effective in inducing an immune response without clinical reactions. The results show that the Oka strain of varicella virus passaged in GPEC and human diploid (WI-38) cells may be used safely and effectively as a live attenuated vaccine.", "contents": "Development of a live attenuated varicella vaccine. The Oka strain of varicella virus, isolated in our labolatory, was serially cultivated in guinea-pig embryo cultures (GPEC), and a considerable amount of cell-free virus was obtained from infected cell. GPEC passage virus at the 6th passage level was used in a small scale field trial. Susceptible children of 1 to 10 years old were injected subcutaneously with 100 to 1,000 PFU of virus. No clinical reactions due to the vaccination were observed in any children, and a high rate of antibody response was obtained with viral doses of more than 200 PFU. Attenuated virus obtained by passage in GPEC was propagated in human diploid (WI-38) cells, and it was also effective in inducing an immune response without clinical reactions. The results show that the Oka strain of varicella virus passaged in GPEC and human diploid (WI-38) cells may be used safely and effectively as a live attenuated vaccine."} {"id": "PMID:167708", "title": "Application of a live attenuated varicella vaccine to hospitalized children and its protective effect on spread of varicella infection.", "content": "Twenty-three hospitalized children with no history of varicella or no detectable complement fixing (CF) antibody, were vaccinated with a live attenuated varicella vaccine (Oka strain) immediately after the occurrence of a case of varicella in a children's ward of hospital. These children suffered from the nephrotic syndrome, nephritis, purulent meningitis, hepatitis etc., and 12 of them were receiving steroid therapy. An antibody response was noticed in all the vaccinated children, with mild fever in 6 and a mild rash in 2 of 6. It was uncertain whether these reactions were due to vaccinatin or to naturally acquired infection modified by vaccination. No other clinical reactions or abnormalities of the blood or urine were detected. Thus the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. In another trial, 16 children with renal diseases were also vaccinated. All the children showed an immune response with no clinical reactions and no abnormalities in blood and urine examinations. Thus live varicella vaccine (Oka strain) can be used safely and effectively for hospitalized children, and its effectiveness in preventing spread of varicella infection was confirmed.", "contents": "Application of a live attenuated varicella vaccine to hospitalized children and its protective effect on spread of varicella infection. Twenty-three hospitalized children with no history of varicella or no detectable complement fixing (CF) antibody, were vaccinated with a live attenuated varicella vaccine (Oka strain) immediately after the occurrence of a case of varicella in a children's ward of hospital. These children suffered from the nephrotic syndrome, nephritis, purulent meningitis, hepatitis etc., and 12 of them were receiving steroid therapy. An antibody response was noticed in all the vaccinated children, with mild fever in 6 and a mild rash in 2 of 6. It was uncertain whether these reactions were due to vaccinatin or to naturally acquired infection modified by vaccination. No other clinical reactions or abnormalities of the blood or urine were detected. Thus the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. In another trial, 16 children with renal diseases were also vaccinated. All the children showed an immune response with no clinical reactions and no abnormalities in blood and urine examinations. Thus live varicella vaccine (Oka strain) can be used safely and effectively for hospitalized children, and its effectiveness in preventing spread of varicella infection was confirmed."} {"id": "PMID:167710", "title": "Multiple cyclic nucleotide phosphodiesterase activities from rat tissues and occurrence of a calcium-plus-magnesium-ion-dependent phosphodiesterase and its protein activator.", "content": "1. Supernatant fluids from rat cerebral cortex, cerebellum, kidney, heart and liver contained more phosphodiesterase activity hydrolysing cyclic GMP than that hydrolysing cyclic AMP when assayed with sub-saturating concentrations of substrate. 2. These activities were resolved into several fractions by Sephadex G-200 gel filtration; no two tissues had similar activity profiles. 3. With every tissue examined, a fraction (fraction II) with a molecular weight of about 150,000 was obtained which hydrolysed cyclic GMP preferentially at sub-saturating substrate concentrations in the presence of micromolar concentration of Ca2+, millimolar concentration of Mg2+ and a protein activator. 4. The activity of fraction II accounted for about 60 percent in liver, more than 80 percent in heart and cerebellum, and almost 100 percent in cerebral cortex of the total activity for cyclic GMP hydrolysis, calculated from the activity profiles. 5. Km values of fraction II samples from kidney, heart and liver for cyclic GMP were 1.3, 1.7 and 5 muM respectively. 6. 3-Isobutyl-1-methylxanthine inhibited hydrolysis of cyclic GMP by fraction II with an I50 value of 3muM for heart and liver and 50 muM for cerebrum. 7. The activator protein, with an estimated molecular weight of about 30,000 was isolated from all the tissues listed in 1.8. The concentrations of activator protein and of the isolated enzyme, fraction II, did not correspond exactly.", "contents": "Multiple cyclic nucleotide phosphodiesterase activities from rat tissues and occurrence of a calcium-plus-magnesium-ion-dependent phosphodiesterase and its protein activator. 1. Supernatant fluids from rat cerebral cortex, cerebellum, kidney, heart and liver contained more phosphodiesterase activity hydrolysing cyclic GMP than that hydrolysing cyclic AMP when assayed with sub-saturating concentrations of substrate. 2. These activities were resolved into several fractions by Sephadex G-200 gel filtration; no two tissues had similar activity profiles. 3. With every tissue examined, a fraction (fraction II) with a molecular weight of about 150,000 was obtained which hydrolysed cyclic GMP preferentially at sub-saturating substrate concentrations in the presence of micromolar concentration of Ca2+, millimolar concentration of Mg2+ and a protein activator. 4. The activity of fraction II accounted for about 60 percent in liver, more than 80 percent in heart and cerebellum, and almost 100 percent in cerebral cortex of the total activity for cyclic GMP hydrolysis, calculated from the activity profiles. 5. Km values of fraction II samples from kidney, heart and liver for cyclic GMP were 1.3, 1.7 and 5 muM respectively. 6. 3-Isobutyl-1-methylxanthine inhibited hydrolysis of cyclic GMP by fraction II with an I50 value of 3muM for heart and liver and 50 muM for cerebrum. 7. The activator protein, with an estimated molecular weight of about 30,000 was isolated from all the tissues listed in 1.8. The concentrations of activator protein and of the isolated enzyme, fraction II, did not correspond exactly."} {"id": "PMID:167711", "title": "Inhibition by ricin of protein synthesis in vitro. Inhibition of the binding of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 to ribosomes.", "content": "The binding of EF2 (elongation factor 2) and of ADP-ribosyl-EF 2 to rat liver ribosomes is inhibited by ricin. This result suggests that the native enzyme and its ADP-ribose derivative have the same or closely related binding sites on the ribosome. The inhibition by ricin of the binding of EF 2 to ribosomes is consistent with the previous observation that ricin affects EF 2-catalysed translocation during polypeptide chain elongation.", "contents": "Inhibition by ricin of protein synthesis in vitro. Inhibition of the binding of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 to ribosomes. The binding of EF2 (elongation factor 2) and of ADP-ribosyl-EF 2 to rat liver ribosomes is inhibited by ricin. This result suggests that the native enzyme and its ADP-ribose derivative have the same or closely related binding sites on the ribosome. The inhibition by ricin of the binding of EF 2 to ribosomes is consistent with the previous observation that ricin affects EF 2-catalysed translocation during polypeptide chain elongation."} {"id": "PMID:167712", "title": "Purification and some properties of a soluble benzene-oxidizing system from a strain of Pseudomonas.", "content": "1. A soluble enzyme system which oxidizes benzene to cis-1,2-dihydroxycyclohexa-3,5-diene (cis-benzene glycol) was obtained from a species of Pseudomonas grown on benzene as the major carbon source. 2. The system was shown to consist of three protein components. Two of these were non-haem-iron proteins of molecular weight approx. 21,000 and approx. 186,000 and the other was a flavoprotein of molecular weight approx. 60,000. 3. Fe2+ and NADH were essential cofactors for benzene oxidation.", "contents": "Purification and some properties of a soluble benzene-oxidizing system from a strain of Pseudomonas. 1. A soluble enzyme system which oxidizes benzene to cis-1,2-dihydroxycyclohexa-3,5-diene (cis-benzene glycol) was obtained from a species of Pseudomonas grown on benzene as the major carbon source. 2. The system was shown to consist of three protein components. Two of these were non-haem-iron proteins of molecular weight approx. 21,000 and approx. 186,000 and the other was a flavoprotein of molecular weight approx. 60,000. 3. Fe2+ and NADH were essential cofactors for benzene oxidation."} {"id": "PMID:167713", "title": "Incorporation of isotopic carbon into cerebral glycogen from non-glucose substrates.", "content": "1. Measurable incorporation of radioactive carbon from [U-14C]pyruvate, [U-14C]-glutamate and [14C]bicarbonate into the glycogen synthesized by brain slices in vitro was demonstrated. 2. The fructose diphosphatase activity of guinea-pig brain was determined and found to be about 0.03 mumol of substrate degraded/min per g of fresh tissue. 3. The specific radioactivity of the glucose carbon from glycogen relative to that of the precursor added to the incubation medium gave approximate values of 0.195 for glucose, 0.006 for pyruvate, 0.039 for glutamate and 0.001 for bicarbonate.", "contents": "Incorporation of isotopic carbon into cerebral glycogen from non-glucose substrates. 1. Measurable incorporation of radioactive carbon from [U-14C]pyruvate, [U-14C]-glutamate and [14C]bicarbonate into the glycogen synthesized by brain slices in vitro was demonstrated. 2. The fructose diphosphatase activity of guinea-pig brain was determined and found to be about 0.03 mumol of substrate degraded/min per g of fresh tissue. 3. The specific radioactivity of the glucose carbon from glycogen relative to that of the precursor added to the incubation medium gave approximate values of 0.195 for glucose, 0.006 for pyruvate, 0.039 for glutamate and 0.001 for bicarbonate."} {"id": "PMID:167714", "title": "Role of glycerol 3-phosphate dehydrogenase in glyceride metabolism. Effect of diet on enzyme activities in chicken liver.", "content": "1. The metabolic role of hepatic NAD-linked glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) was investigated vis-a-vis glyceride synthesis, glyceride degradation and the maintainence of the NAD redox state. 2. Five-week-old chickens were placed on five dietary regimes: a control group, a group on an increased-carbohydrate-lowered-fat diet, a group on a high-fat-lowered-carbohydrate diet, a starved group and a starved-refed group. In each group the specific activity (mumol/min per g wet wt. of tissue) of hepatic glycerol 3-phosphate dehydrogenase was compared with the activities of the beta-oxoacyl-(acyl-carrier protein) reductase component of fatty acid synthetase, glycerol kinase (EC 2.7.1.30) and lactate dehydrogenase (EC 1.1.1.27). 3. During starvation, the activities of glycerol 3-phosphate dehydrogenase, glycerol kinase and lactate dehydrogenase rose significantly. After re-feeding these activities returned to near normal. All three activities rose slightly on the high-fat diet. Lactate dehydrogenase activity rose slightly, whereas those of the other two enzymes fell slightly on the increased-carbohydrate-lowered-fat diet. 4. The activity of the beta-oxoacyl-(acyl-carrier protein) reductase component of fatty acid synthetase, a lipid-synthesizing enzyme, contrasted strikingly with the other three enzyme activities. Its activity was slightly elevated on the increased-carbohydrate diet and significantly diminished on the high-fat diet and during starvation. 5. The changes in activity of the chicken liver isoenzyme of glycerol 3-phosphate dehydrogenase in response to dietary stresses suggest that the enzyme has an important metabolic role other than or in addition to glyceride biosynthesis.", "contents": "Role of glycerol 3-phosphate dehydrogenase in glyceride metabolism. Effect of diet on enzyme activities in chicken liver. 1. The metabolic role of hepatic NAD-linked glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) was investigated vis-a-vis glyceride synthesis, glyceride degradation and the maintainence of the NAD redox state. 2. Five-week-old chickens were placed on five dietary regimes: a control group, a group on an increased-carbohydrate-lowered-fat diet, a group on a high-fat-lowered-carbohydrate diet, a starved group and a starved-refed group. In each group the specific activity (mumol/min per g wet wt. of tissue) of hepatic glycerol 3-phosphate dehydrogenase was compared with the activities of the beta-oxoacyl-(acyl-carrier protein) reductase component of fatty acid synthetase, glycerol kinase (EC 2.7.1.30) and lactate dehydrogenase (EC 1.1.1.27). 3. During starvation, the activities of glycerol 3-phosphate dehydrogenase, glycerol kinase and lactate dehydrogenase rose significantly. After re-feeding these activities returned to near normal. All three activities rose slightly on the high-fat diet. Lactate dehydrogenase activity rose slightly, whereas those of the other two enzymes fell slightly on the increased-carbohydrate-lowered-fat diet. 4. The activity of the beta-oxoacyl-(acyl-carrier protein) reductase component of fatty acid synthetase, a lipid-synthesizing enzyme, contrasted strikingly with the other three enzyme activities. Its activity was slightly elevated on the increased-carbohydrate diet and significantly diminished on the high-fat diet and during starvation. 5. The changes in activity of the chicken liver isoenzyme of glycerol 3-phosphate dehydrogenase in response to dietary stresses suggest that the enzyme has an important metabolic role other than or in addition to glyceride biosynthesis."} {"id": "PMID:167715", "title": "Electron-paramagnetic-resonance spectroscopy studies of iron-sulphur centres of submitochondrial particles from iron- and sulphur-deficient. Candida utilis.", "content": "1. Measurements were made at 12 degrees K of the electron-paramagnetic-resonance (e.p.r.) spectra of submitochondrial particles from Candida utilis cells grown under conditions that alter the amount of the mitochondrial NADH dehydrogenase (EC 1.6.99.3). 2. Iron-limited growth decreases the extent of iron-sulphur e.p.r. signals to undetectable values that are less than 1 percent of those normally found with glycerol-limited growth. 3. Small but significant signals attributable to the NADH dehydrogenase were detected in submitochondrial particles from sulphate-limited cells. 4. Measurements made on submitochondrial particles prepared from these and other phenotypically modified cells lead us to conclude that the presence of low-temperature e.p.r.-detectable iron-sulphur centres attributable to the NADH dehydrogenase are necessary but not sufficient for the coupling of ATP synthesis to the NADH dehydrogenase reaction in the mitochondrial membrane of C. utilis. 6. The amplitude of the g=2.01 signal observed in non-reduced submitochondrial particles is approximately tenfold diminished by iron limitation but not significantly altered by sulphate limitation.", "contents": "Electron-paramagnetic-resonance spectroscopy studies of iron-sulphur centres of submitochondrial particles from iron- and sulphur-deficient. Candida utilis. 1. Measurements were made at 12 degrees K of the electron-paramagnetic-resonance (e.p.r.) spectra of submitochondrial particles from Candida utilis cells grown under conditions that alter the amount of the mitochondrial NADH dehydrogenase (EC 1.6.99.3). 2. Iron-limited growth decreases the extent of iron-sulphur e.p.r. signals to undetectable values that are less than 1 percent of those normally found with glycerol-limited growth. 3. Small but significant signals attributable to the NADH dehydrogenase were detected in submitochondrial particles from sulphate-limited cells. 4. Measurements made on submitochondrial particles prepared from these and other phenotypically modified cells lead us to conclude that the presence of low-temperature e.p.r.-detectable iron-sulphur centres attributable to the NADH dehydrogenase are necessary but not sufficient for the coupling of ATP synthesis to the NADH dehydrogenase reaction in the mitochondrial membrane of C. utilis. 6. The amplitude of the g=2.01 signal observed in non-reduced submitochondrial particles is approximately tenfold diminished by iron limitation but not significantly altered by sulphate limitation."} {"id": "PMID:167716", "title": "Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens.", "content": "1. Various lectins [phaseolus vulgaris phytohaemagglutinin, Glycine max (soy-bean) agglutinin, Triticum vulgaris (wheat-germ) agglutinin and Axinella polyploides agglutinin] and antibodies to pig Ig (immunoglobulin) that are found by pig lymphocytes were assessed in terms of their capacities to stimulate lymphocyte transformation and to enhance phosphatidylinositol turnover. Transformation was measured after 45h of culture by incorporation of [6-(3)H]thymidine into DNA, whereas phosphatidylinositol metabolism was assessed after 1h of cultuis and G. max agglutinins and rabbit antibodies to pig Ig) increased phosphatidylinositol turnover, but non-transforming agents (T. vulgaris and A. polyploides agglutinins and Fab fragments of rabbit antibodies to pig Ig) failed to induce any significant enhancement. Subsequent cross-linkage of the bound, non-transforming Fab fragments with a goat antiserum to rabbit Ig stimulated transformation and phosphatidylinositol turnover. 3. Each transforming agent gave characteristic optimal dose responses that were similar for both phosphatidylinositol turnover and transformation. 4. The results indicate that activation of T- and B-lymphocytes is accompanied by enhanced phosphatidylinositol turnover and that in the case of B-cells this enhancement depends on the cross-linkage of surface receptors. They are consistent with the proposal that turnover represents an essential early step in the transformation process.", "contents": "Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens. 1. Various lectins [phaseolus vulgaris phytohaemagglutinin, Glycine max (soy-bean) agglutinin, Triticum vulgaris (wheat-germ) agglutinin and Axinella polyploides agglutinin] and antibodies to pig Ig (immunoglobulin) that are found by pig lymphocytes were assessed in terms of their capacities to stimulate lymphocyte transformation and to enhance phosphatidylinositol turnover. Transformation was measured after 45h of culture by incorporation of [6-(3)H]thymidine into DNA, whereas phosphatidylinositol metabolism was assessed after 1h of cultuis and G. max agglutinins and rabbit antibodies to pig Ig) increased phosphatidylinositol turnover, but non-transforming agents (T. vulgaris and A. polyploides agglutinins and Fab fragments of rabbit antibodies to pig Ig) failed to induce any significant enhancement. Subsequent cross-linkage of the bound, non-transforming Fab fragments with a goat antiserum to rabbit Ig stimulated transformation and phosphatidylinositol turnover. 3. Each transforming agent gave characteristic optimal dose responses that were similar for both phosphatidylinositol turnover and transformation. 4. The results indicate that activation of T- and B-lymphocytes is accompanied by enhanced phosphatidylinositol turnover and that in the case of B-cells this enhancement depends on the cross-linkage of surface receptors. They are consistent with the proposal that turnover represents an essential early step in the transformation process."} {"id": "PMID:167717", "title": "Lack of relationship between activity of chromatin-bound proteinase and cell growth rates.", "content": "Proteinase associated with chromatin isolated from liver and hepatoma of rat is stimulated by salt, and, of the histone fractions, lysine-rich (F1) histone is preferentially degraded by this enzyme at an ionic strength comparable with that found in the nucleus. However, there appears to be no strict relationship between the activity of the proteinase and growth rates of hepatomas. Chromatin isolated from a fast-growing tumour, Ehrlich ascites carcinoma, shows no apparent proteinase activity in the presence of salt.", "contents": "Lack of relationship between activity of chromatin-bound proteinase and cell growth rates. Proteinase associated with chromatin isolated from liver and hepatoma of rat is stimulated by salt, and, of the histone fractions, lysine-rich (F1) histone is preferentially degraded by this enzyme at an ionic strength comparable with that found in the nucleus. However, there appears to be no strict relationship between the activity of the proteinase and growth rates of hepatomas. Chromatin isolated from a fast-growing tumour, Ehrlich ascites carcinoma, shows no apparent proteinase activity in the presence of salt."} {"id": "PMID:167718", "title": "The properties of hydrogen peroxide production under hyperoxic and hypoxic conditions of perfused rat liver.", "content": "The properties of H2O2 production in the \"haemoglobin-free\", \"non-circulatory\" perfused liver of rats were examined. The H2O2 production with 1 mM-lactate and 0.15 mM-pyruvate was 82nmol/min per g of liver or 333nmol/min per 100g body wt. in the liver of fed rats at 30 degrees C. This rate decreased to almost half in the livers of starved and phenobarbital-pretreated rats. When H2O2 production was stimulated by urate infusion, almost all of the H2O2 produced by the uricase reaction was decomposed by the catalase reaction. During the demethylation reaction of aminopyrine, no change in H2O2 production was detected by the present method; thus microsomal H2O2 production observed in isolated subcellular fractions appeared not to contribute significantly to the H2O2 production in the whole organ. Whereas the rate of the glycolate-dependent H2O2 production was halved at an intracellular O2 concentration that caused a 10 percent increase in the reduction state of cytochrome c, the half-maximal rate of H2O2 production with lactate and pyruvate was observed at an O2 concentration that caused a 40 percent increase in the reduction state of cytochrome c in the liver. No further increase in the rates of H2O2 production was obtained by increasing O2 pressure up to 5 times 10(5) Pa. The rate of ethanol oxidation through the catalase \"peroxidatic\" reaction varied, depending on the substrate availability. The maximal capability of this pathway in ethanol oxidation reached approx. 1.5 mumol/min per g of liver, when a mixture of urate, glycollate and octanoate was infused to enhance H2O2 production.", "contents": "The properties of hydrogen peroxide production under hyperoxic and hypoxic conditions of perfused rat liver. The properties of H2O2 production in the \"haemoglobin-free\", \"non-circulatory\" perfused liver of rats were examined. The H2O2 production with 1 mM-lactate and 0.15 mM-pyruvate was 82nmol/min per g of liver or 333nmol/min per 100g body wt. in the liver of fed rats at 30 degrees C. This rate decreased to almost half in the livers of starved and phenobarbital-pretreated rats. When H2O2 production was stimulated by urate infusion, almost all of the H2O2 produced by the uricase reaction was decomposed by the catalase reaction. During the demethylation reaction of aminopyrine, no change in H2O2 production was detected by the present method; thus microsomal H2O2 production observed in isolated subcellular fractions appeared not to contribute significantly to the H2O2 production in the whole organ. Whereas the rate of the glycolate-dependent H2O2 production was halved at an intracellular O2 concentration that caused a 10 percent increase in the reduction state of cytochrome c, the half-maximal rate of H2O2 production with lactate and pyruvate was observed at an O2 concentration that caused a 40 percent increase in the reduction state of cytochrome c in the liver. No further increase in the rates of H2O2 production was obtained by increasing O2 pressure up to 5 times 10(5) Pa. The rate of ethanol oxidation through the catalase \"peroxidatic\" reaction varied, depending on the substrate availability. The maximal capability of this pathway in ethanol oxidation reached approx. 1.5 mumol/min per g of liver, when a mixture of urate, glycollate and octanoate was infused to enhance H2O2 production."} {"id": "PMID:167719", "title": "The selectivity and stoicheiometry of membrane binding sites for polyribosomes, ribosomes and ribosomal subunits in vitro.", "content": "Differences in the binding sites for polyribosomes, template-depleted ribosomes and large ribosomal subunits were found in microsomal derivatives of the rough endoplasmic reticulum. 1. The stoicheiometry of polyribosome and ribosome interaction in vitro with membranes was shown to be influenced by the relative concentration of interactants and the duration of their mixing. Large ribosomal subunits required a more prolonged mixing schedule to achieve saturation of membranes than did polyribosomes. 2. By using a procedure which minimized the effects on binidng by the stoicheiometric variables, competition between populations of polyribosomes, ribosomes and subunits for membrane sites showed that subunits, and to a lesser extent ribosomes, failed to block polyribosome attachment. 3. Polyribosomes isolated from liver, kidney and hepatoma 5123C entirely bound to a common membrane site, but some polyribosomes from myeloma MOPC-21 bound to other sites, perhaps influenced by their unique nascent proteins. 4. Subunit-binding sites appear on rough membranes only after endogenous polyribosomes have been removed, but no evidence that resulting changes in surface constituents are responsible was found. Large-subunit binding was largely abolished by lowering MgC12 concentration of 0.1 mM, whereas under the same conditions polyribosome binding was undiminished. 5. The large-subunit site appears to be distinct from the polyribosome site not only in the restriction of its affinity for particles but also spatially, to the extent that bound subunits do not hinder access of polyribosomes to their sites.", "contents": "The selectivity and stoicheiometry of membrane binding sites for polyribosomes, ribosomes and ribosomal subunits in vitro. Differences in the binding sites for polyribosomes, template-depleted ribosomes and large ribosomal subunits were found in microsomal derivatives of the rough endoplasmic reticulum. 1. The stoicheiometry of polyribosome and ribosome interaction in vitro with membranes was shown to be influenced by the relative concentration of interactants and the duration of their mixing. Large ribosomal subunits required a more prolonged mixing schedule to achieve saturation of membranes than did polyribosomes. 2. By using a procedure which minimized the effects on binidng by the stoicheiometric variables, competition between populations of polyribosomes, ribosomes and subunits for membrane sites showed that subunits, and to a lesser extent ribosomes, failed to block polyribosome attachment. 3. Polyribosomes isolated from liver, kidney and hepatoma 5123C entirely bound to a common membrane site, but some polyribosomes from myeloma MOPC-21 bound to other sites, perhaps influenced by their unique nascent proteins. 4. Subunit-binding sites appear on rough membranes only after endogenous polyribosomes have been removed, but no evidence that resulting changes in surface constituents are responsible was found. Large-subunit binding was largely abolished by lowering MgC12 concentration of 0.1 mM, whereas under the same conditions polyribosome binding was undiminished. 5. The large-subunit site appears to be distinct from the polyribosome site not only in the restriction of its affinity for particles but also spatially, to the extent that bound subunits do not hinder access of polyribosomes to their sites."} {"id": "PMID:167720", "title": "The control of tricarboxylate-cycle oxidations in blowfly flight muscle. The oxidized and reduced nicotinamide-adenine dinucleotide content of flight muscle and isolated mitochondria, the adenosine triphosphate and adenosine diphosphate content of mitochondria, and the energy status of the mitochondria during controlled respiration.", "content": "1. A study is presented of the mitochondrial NADH content during controlled (state 4) and active (state 3) pyruvate oxidation by blowfly flight-muscle mitochondria. The results confirm and extend those of an earlier study (Hansford, 1972), which indicated an increased reduction in state 3. Nicotinamide nucleotide is normally highly oxidized during state 4; however, there can be substantial reduction in the presence of carnitine or high concentrations of proline, or on lengthy incubation in the presence of either of the systems used to generate intramitochondrial tricarboxylate-cycle intermediate. 2. Omission of phosphate leads to substantial reduction and this can be reversed by adding phosphate or acetate. 3. Estimations of NAD-+ and NADH in fly thoraces show a marked increase in NADH on flight, tending to corroborate the results of mitochondrial experiments and testifying to the importance of dehydrogenase activation in this tissue. 4. Determination of intramitochondrial adenine nucleotides reveals a total of 4-5 nmol/mg of protein, and an ADP content of less than 0.1 nmol/mg during state 4 oxidation of pyruvate and proline. ATP content is found to increase slowly during state 4 and this is attributed to the net phosphorylation of AMP. 5. The uncoupling agent carbonyl cyanide p=trifluoromethoxyphenylhydrazone leads to hydrolysis of some, but not all, of the mitochondrial ATP. Studies of mitochondrial ATPase (adenosine triphosphatase), measured by external pH change, show that it is inactive unless the mitochondria are allowed to respire for several minutes in state 4 in the presence of phosphate before the addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone. It is suggested that phosphate uptake is essential for maximal ATPase activity. 6. Studies of the fluorescence of the fluorochrome 8-anilino-1-naphthalensulphonic acid suggest that the energy status of the mitochondrion is high during state 4-pyruvate oxidattion, and decrease slightly in state 3. The implications of these findings are discussed.", "contents": "The control of tricarboxylate-cycle oxidations in blowfly flight muscle. The oxidized and reduced nicotinamide-adenine dinucleotide content of flight muscle and isolated mitochondria, the adenosine triphosphate and adenosine diphosphate content of mitochondria, and the energy status of the mitochondria during controlled respiration. 1. A study is presented of the mitochondrial NADH content during controlled (state 4) and active (state 3) pyruvate oxidation by blowfly flight-muscle mitochondria. The results confirm and extend those of an earlier study (Hansford, 1972), which indicated an increased reduction in state 3. Nicotinamide nucleotide is normally highly oxidized during state 4; however, there can be substantial reduction in the presence of carnitine or high concentrations of proline, or on lengthy incubation in the presence of either of the systems used to generate intramitochondrial tricarboxylate-cycle intermediate. 2. Omission of phosphate leads to substantial reduction and this can be reversed by adding phosphate or acetate. 3. Estimations of NAD-+ and NADH in fly thoraces show a marked increase in NADH on flight, tending to corroborate the results of mitochondrial experiments and testifying to the importance of dehydrogenase activation in this tissue. 4. Determination of intramitochondrial adenine nucleotides reveals a total of 4-5 nmol/mg of protein, and an ADP content of less than 0.1 nmol/mg during state 4 oxidation of pyruvate and proline. ATP content is found to increase slowly during state 4 and this is attributed to the net phosphorylation of AMP. 5. The uncoupling agent carbonyl cyanide p=trifluoromethoxyphenylhydrazone leads to hydrolysis of some, but not all, of the mitochondrial ATP. Studies of mitochondrial ATPase (adenosine triphosphatase), measured by external pH change, show that it is inactive unless the mitochondria are allowed to respire for several minutes in state 4 in the presence of phosphate before the addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone. It is suggested that phosphate uptake is essential for maximal ATPase activity. 6. Studies of the fluorescence of the fluorochrome 8-anilino-1-naphthalensulphonic acid suggest that the energy status of the mitochondrion is high during state 4-pyruvate oxidattion, and decrease slightly in state 3. The implications of these findings are discussed."} {"id": "PMID:167721", "title": "The influence of environmental agents on prostaglandin biosynthesis and metabolism in the lung. Inhibition of lung 15-hydroxyprostaglandin dehydrogenase by exposure of guinea pigs to 100 per cent oxygen at atmospheric pressure.", "content": "Enzymes in the 100 000g supernatant fraction of guinea-pig lungs, in the presence of NAD-+, converted PGF-2 alpha (prostaglanding F-2 alpha) into a less-polar compound. The u.v. spectrum of this metabolite showed a strong absorption band at 230 nm, which is characteristic of a carbonyl group in conjugation with a double bond. Reduction of this metabolite with NaBH4 resulted in a compound that behaved like PGF2 ALPHA on t.l.c. and g.l.c. From this evidence we concluded that PGF2alpha is metabolized in vitro to 15-oxo-PGF2 alpha by the NAD-+-dependent prostaglandin dehydrogenase system of guinea-pig lung. The effect of exposure of the animal to SO-2 and O2 on the rate of prostaglanding biosynthesis and catabolism by lung fractions in vitro was studied. Exposure of guinea pigs to 500 p.m. of SO2 for 5h or to 50p.p.m for 9 days (6h/day) did not alter the production or degradation of prostaglandings by lung fractions in vitro. In contrast, exposure of guinea pigs to 100% O2 for 48 h inhibited the rate of prostaglanding metabolism in vitro by 60-70% without significantly altering the rate of biosynthesis by lung fractions. Inhibition of prostaglandin dehydrogenase activity in vitro by lung fractions after exposure of the animal to O2 was dependent on the duration of exposure. Gluthathione S-aryltransferase and catechol O-methyltransferase activites of guinea-pig lung 100 000g supernatant were unaltered by exposure of the animal to O2. Thus it appears that inhibition of pulmonary prostaglandin dehydrogenase by exposure of the animal to O2 is not the result of a general toxic response. It was postulated that the inhibition of prostaglanding dehydrogenase may occur after exposure of the animal to other oxidant gases.", "contents": "The influence of environmental agents on prostaglandin biosynthesis and metabolism in the lung. Inhibition of lung 15-hydroxyprostaglandin dehydrogenase by exposure of guinea pigs to 100 per cent oxygen at atmospheric pressure. Enzymes in the 100 000g supernatant fraction of guinea-pig lungs, in the presence of NAD-+, converted PGF-2 alpha (prostaglanding F-2 alpha) into a less-polar compound. The u.v. spectrum of this metabolite showed a strong absorption band at 230 nm, which is characteristic of a carbonyl group in conjugation with a double bond. Reduction of this metabolite with NaBH4 resulted in a compound that behaved like PGF2 ALPHA on t.l.c. and g.l.c. From this evidence we concluded that PGF2alpha is metabolized in vitro to 15-oxo-PGF2 alpha by the NAD-+-dependent prostaglandin dehydrogenase system of guinea-pig lung. The effect of exposure of the animal to SO-2 and O2 on the rate of prostaglanding biosynthesis and catabolism by lung fractions in vitro was studied. Exposure of guinea pigs to 500 p.m. of SO2 for 5h or to 50p.p.m for 9 days (6h/day) did not alter the production or degradation of prostaglandings by lung fractions in vitro. In contrast, exposure of guinea pigs to 100% O2 for 48 h inhibited the rate of prostaglanding metabolism in vitro by 60-70% without significantly altering the rate of biosynthesis by lung fractions. Inhibition of prostaglandin dehydrogenase activity in vitro by lung fractions after exposure of the animal to O2 was dependent on the duration of exposure. Gluthathione S-aryltransferase and catechol O-methyltransferase activites of guinea-pig lung 100 000g supernatant were unaltered by exposure of the animal to O2. Thus it appears that inhibition of pulmonary prostaglandin dehydrogenase by exposure of the animal to O2 is not the result of a general toxic response. It was postulated that the inhibition of prostaglanding dehydrogenase may occur after exposure of the animal to other oxidant gases."} {"id": "PMID:167722", "title": "Properties of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesized in hepatoma cells in the presence of amino acid analogues.", "content": "Phosphoenolpyruvate carboxykinase (GTP) was induced by a combination of dibutyryl cyclic AMP, theophyline and dexamethasone in Reuber H35 hepatoma cells under conditions where an amino acid in the medium was replaced by an appropriate analogue. 2. With canavanine replacing arginine or with 5-fluorotryptophan or 6-fluorotryptophan replacing tryptophan the induced enzyme had a lower catalytic activity-relative to antibody reactivity. 3. These aberrant enzyme molecules were heat-labile in vitro. 4. Measurements of enzyme degradation in vivo indicated that the canavanine-containing enzyme and the 6-fluorotryptophan-containing enzyme were degraded more rapidly than the enzyme containing all natural amino acids.", "contents": "Properties of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesized in hepatoma cells in the presence of amino acid analogues. Phosphoenolpyruvate carboxykinase (GTP) was induced by a combination of dibutyryl cyclic AMP, theophyline and dexamethasone in Reuber H35 hepatoma cells under conditions where an amino acid in the medium was replaced by an appropriate analogue. 2. With canavanine replacing arginine or with 5-fluorotryptophan or 6-fluorotryptophan replacing tryptophan the induced enzyme had a lower catalytic activity-relative to antibody reactivity. 3. These aberrant enzyme molecules were heat-labile in vitro. 4. Measurements of enzyme degradation in vivo indicated that the canavanine-containing enzyme and the 6-fluorotryptophan-containing enzyme were degraded more rapidly than the enzyme containing all natural amino acids."} {"id": "PMID:167723", "title": "Increased degradation rates of protein synthesized in hepatoma cells in the presence of amino acid analogues.", "content": "1. Reuber H35 hepatoma cells incorporate the arginine analogue canavanine into cell protein when arginine is omitted from the incubation medium. 2. By labelling arginine-containing proteins with (14-C)leucine and then canavanine-containing proteins with (3-H)leucine in the same cells, it is possible to measure the degradation of both types of protein during a subsequent 'chase' period. With this technique it has been shown that canavanine-containing proteins are degraded at a rate severalfold greater than normal proteins. Comparable results were found when 6-fluorotryptophan was used as an analogue to tryptophan. 3. Control experiments in which the labelling order was reversed or where the animo acid and its analogue were incubated in separate cell cultures support the conclusion that abberrant proteins are rapidly degraded in vivo.", "contents": "Increased degradation rates of protein synthesized in hepatoma cells in the presence of amino acid analogues. 1. Reuber H35 hepatoma cells incorporate the arginine analogue canavanine into cell protein when arginine is omitted from the incubation medium. 2. By labelling arginine-containing proteins with (14-C)leucine and then canavanine-containing proteins with (3-H)leucine in the same cells, it is possible to measure the degradation of both types of protein during a subsequent 'chase' period. With this technique it has been shown that canavanine-containing proteins are degraded at a rate severalfold greater than normal proteins. Comparable results were found when 6-fluorotryptophan was used as an analogue to tryptophan. 3. Control experiments in which the labelling order was reversed or where the animo acid and its analogue were incubated in separate cell cultures support the conclusion that abberrant proteins are rapidly degraded in vivo."} {"id": "PMID:167724", "title": "Dynamics of oestrogen-receptor distribution between the cytosol and nuclear fractions of immature rat uterus after oestradiol administration.", "content": "1. The nuclear-myofibrilar (800g pellet) fraction of the uterus from immature (22-23 days old) rats not exposed to oestrogen exhibits saturable binding of oestradiol. The nuclear binding capacity represents approximately 10% of that of the cytosol fraction (approx. 3.5 fmol/mug of DNA). The predominant part (0.3.5 fmol/mug of DNA) of the nuclear binind sites are present in the residual pellet after extraction with 0.5 M-KC1. 2. By using an exchange technique in vitro, determinations of the nuclear binding sites have been carried out after administration of 1 mug of oestradiol in vivo. Within 0.5h after the hormone injection, the concentration of nuclear bindng sites increased to approx. 0.4 fmol/mug of DNA in the 0.5 M-KC1-extractable fraction, and to approx. 1.2 fmol/mug of DNA in the residual fraction. Meanwhile the cytosol oestrogen-receptor concentration decreased to approx. 10% of its initial value. In the following period from 0.5 h after the oestradiol injection onwards, the concentration of nuclear oestrogen receptors decreased with halflife values of approx. 140 and 200 min for the KC1(0.5 M)-extractable and residual form respectively. At the same time, the cytosol receptor concentration increased to reach approx. 50% of the initial value by the 6h. This increase could not be blocked by cycloheximide. The initial concentration of cytosol receptor was restored approx. 11h after the injection and the increase during the 6-11h period was sensitive to cycloheximide inhibition, suggesting protein-synthesis-dependence of the process. 3. With the (more) physiological dose of oestradiol (0.1 mug), the decrease the cytosol receptor was only 50% by 4h and this was followed by a period (up to 12h after injection) during which the initial concentration was restored. During this period the increase of the receptor can be blocked by cycloheximide.", "contents": "Dynamics of oestrogen-receptor distribution between the cytosol and nuclear fractions of immature rat uterus after oestradiol administration. 1. The nuclear-myofibrilar (800g pellet) fraction of the uterus from immature (22-23 days old) rats not exposed to oestrogen exhibits saturable binding of oestradiol. The nuclear binding capacity represents approximately 10% of that of the cytosol fraction (approx. 3.5 fmol/mug of DNA). The predominant part (0.3.5 fmol/mug of DNA) of the nuclear binind sites are present in the residual pellet after extraction with 0.5 M-KC1. 2. By using an exchange technique in vitro, determinations of the nuclear binding sites have been carried out after administration of 1 mug of oestradiol in vivo. Within 0.5h after the hormone injection, the concentration of nuclear bindng sites increased to approx. 0.4 fmol/mug of DNA in the 0.5 M-KC1-extractable fraction, and to approx. 1.2 fmol/mug of DNA in the residual fraction. Meanwhile the cytosol oestrogen-receptor concentration decreased to approx. 10% of its initial value. In the following period from 0.5 h after the oestradiol injection onwards, the concentration of nuclear oestrogen receptors decreased with halflife values of approx. 140 and 200 min for the KC1(0.5 M)-extractable and residual form respectively. At the same time, the cytosol receptor concentration increased to reach approx. 50% of the initial value by the 6h. This increase could not be blocked by cycloheximide. The initial concentration of cytosol receptor was restored approx. 11h after the injection and the increase during the 6-11h period was sensitive to cycloheximide inhibition, suggesting protein-synthesis-dependence of the process. 3. With the (more) physiological dose of oestradiol (0.1 mug), the decrease the cytosol receptor was only 50% by 4h and this was followed by a period (up to 12h after injection) during which the initial concentration was restored. During this period the increase of the receptor can be blocked by cycloheximide."} {"id": "PMID:167725", "title": "The properties and extracellular location of 5'-nucleotidase of the rat fat-cell plasma membrane.", "content": "1. A phosphohydrolase specific for 5'-nucleotides was characterized by using a particulate fraction from isolated fat-cells. 2. The activity of intact cells towards 5'-AMP was studied. 3. The activity in either situation had the same KM for AMP (45 muM) and was inhibited by low concentrations of ATP (less than 50 muM), but less potently by the ATP analogues AMP-P(CH2)P(adenylyl (beta gamma-methylene)diphosphonate) and AMP-P)NH)P (adenylylimidodiphosphate). 4. Homogenization of intact fat-cells caused no increase in activity and at least 85% of the activity was recovered in the particulate preparation. 5. The preparation of fat-cells used in this work was not freely permeable to AMP. 6. The ability of intact fat-cells to hydrolyse AMP implies that 5'-nucleotidase is an ectoenzyme in fat-cells. 7. Concentrations of ATP 100 times lower than intracellular concentrations inhibit the enzyme when added extracellularly to intact fat-cells, implying that this effect is also medicated at the extracellular face of the membrane. 8. Antibodies raised to whole liver cells and whole fat-cells inhibit 5'-nucleotidase in intact cells. 9. Incubation of intact fat-cells with adrenaline (1 mug/ml) or insulin (50 mui.u./ml) failed to alter the KM or Vmax. of the enzyme.", "contents": "The properties and extracellular location of 5'-nucleotidase of the rat fat-cell plasma membrane. 1. A phosphohydrolase specific for 5'-nucleotides was characterized by using a particulate fraction from isolated fat-cells. 2. The activity of intact cells towards 5'-AMP was studied. 3. The activity in either situation had the same KM for AMP (45 muM) and was inhibited by low concentrations of ATP (less than 50 muM), but less potently by the ATP analogues AMP-P(CH2)P(adenylyl (beta gamma-methylene)diphosphonate) and AMP-P)NH)P (adenylylimidodiphosphate). 4. Homogenization of intact fat-cells caused no increase in activity and at least 85% of the activity was recovered in the particulate preparation. 5. The preparation of fat-cells used in this work was not freely permeable to AMP. 6. The ability of intact fat-cells to hydrolyse AMP implies that 5'-nucleotidase is an ectoenzyme in fat-cells. 7. Concentrations of ATP 100 times lower than intracellular concentrations inhibit the enzyme when added extracellularly to intact fat-cells, implying that this effect is also medicated at the extracellular face of the membrane. 8. Antibodies raised to whole liver cells and whole fat-cells inhibit 5'-nucleotidase in intact cells. 9. Incubation of intact fat-cells with adrenaline (1 mug/ml) or insulin (50 mui.u./ml) failed to alter the KM or Vmax. of the enzyme."} {"id": "PMID:167726", "title": "Metabolic interactions of glucose, acetoacetate and adrenaline in rat submaxillary gland in vitro.", "content": "1. The metabolic interactions between glucose, acetoacetate and adrenaline were studied in submaxillary-gland slices. 2. Acetoacetate (2.5 mM) inhibited glucose removal by 22% and entry of glucose carbon into the tricarboxylic acid cycle by 54%. 3. Acetoacetate caused an increase in (glucose 6-phosphate) together with an increase in (citrate), a finding that suggests that the phosphofructokinase step might be inhibited by the elevated (citrate). Support for this suggestion was obtained in experiments in which fluoracetate was used to elevate (citrate). 4. A further site of action of acetoacetate at the pyruvate dehydrogenase step was suggested by an increase in the lactate+pyruvate pool, and the finding that pyruvate removal and (3-14C)pyruvate oxidation were inhibited by acetoacetate. 5. Adrenaline, a stimulator of secretion by this tissue, increased glucose removal by 25%. Adrenaline increased glucose removal to the same extent when acetoacetate was also present in the incubation medium. In both cases the increase was accompanied by a fall in (glucose 6-phosphate). 6. Adrenaline also overcame the inhibition of pyruvate removal caused by acetoacetate. 7. The tissue (ATP) decreased by about 50% on addition of adrenaline, and a similar fall was observed in vivo after adrenergic stimulation by isoproterenol. 8. Omission of Ca-2+ from the medium prevented the fall in (glucose 6-phosphate) and (ATP) caused by adrenaline, although adrenaline was still able to stimulate glucose removal. The inhibitory effect of acetoacetate on gluocse removal was reversed by adrenaline, but there was no stimulation above the control rates. Inhibition of pyruvate removal by acetoacetate was not overcome by adrenaline in the absence of Ca-2+. 9. Dibutyryl cyclic AMP had no effect on glucose removal or on (ATP). 10. Possible mechanisms by which adrenaline can bring about its metabolic effects are discussed.", "contents": "Metabolic interactions of glucose, acetoacetate and adrenaline in rat submaxillary gland in vitro. 1. The metabolic interactions between glucose, acetoacetate and adrenaline were studied in submaxillary-gland slices. 2. Acetoacetate (2.5 mM) inhibited glucose removal by 22% and entry of glucose carbon into the tricarboxylic acid cycle by 54%. 3. Acetoacetate caused an increase in (glucose 6-phosphate) together with an increase in (citrate), a finding that suggests that the phosphofructokinase step might be inhibited by the elevated (citrate). Support for this suggestion was obtained in experiments in which fluoracetate was used to elevate (citrate). 4. A further site of action of acetoacetate at the pyruvate dehydrogenase step was suggested by an increase in the lactate+pyruvate pool, and the finding that pyruvate removal and (3-14C)pyruvate oxidation were inhibited by acetoacetate. 5. Adrenaline, a stimulator of secretion by this tissue, increased glucose removal by 25%. Adrenaline increased glucose removal to the same extent when acetoacetate was also present in the incubation medium. In both cases the increase was accompanied by a fall in (glucose 6-phosphate). 6. Adrenaline also overcame the inhibition of pyruvate removal caused by acetoacetate. 7. The tissue (ATP) decreased by about 50% on addition of adrenaline, and a similar fall was observed in vivo after adrenergic stimulation by isoproterenol. 8. Omission of Ca-2+ from the medium prevented the fall in (glucose 6-phosphate) and (ATP) caused by adrenaline, although adrenaline was still able to stimulate glucose removal. The inhibitory effect of acetoacetate on gluocse removal was reversed by adrenaline, but there was no stimulation above the control rates. Inhibition of pyruvate removal by acetoacetate was not overcome by adrenaline in the absence of Ca-2+. 9. Dibutyryl cyclic AMP had no effect on glucose removal or on (ATP). 10. Possible mechanisms by which adrenaline can bring about its metabolic effects are discussed."} {"id": "PMID:167727", "title": "Differential effects of lipid depletion on membrane sodium-plus-potassium ion-dependent adenosine triphosphatase and potassium ion-dependent phosphatase.", "content": "The phospholipid-dependence of the (Na-++K-+)-dependent ATPase (adenosine triphosphatase) (EC 3.6.1.3) and associated K-+-dependent phosphatase activity (EC 3.6.1.7) have been compared. Unlike the (Na-++K-+)-dependent ATPase activities, the K-+-dependent phosphatase activities of a number of different preparations were not closely correlated with their total phospholipid contents. After partial lipid depletion with a single extraction in Lubrol W the residual ATPase and phosphatase activities were correlated, but their magnitudes were quite different: on average only about 5% of the former remained compared with 50% of the latter. A similar differential effect on these activities was found after extraction with deoxycholate. In contrast with the ATPase, consistent restoration of the phosphatase activity of Lubrol-extracted enzymes by added exogenous phospholipids was not observed. We conclude that, although the K-+-dependent phosphatase may be lipid-dependent, the lipid requirement must be different from that of the complete ATPase system, and this difference should help investigations of their relationship.", "contents": "Differential effects of lipid depletion on membrane sodium-plus-potassium ion-dependent adenosine triphosphatase and potassium ion-dependent phosphatase. The phospholipid-dependence of the (Na-++K-+)-dependent ATPase (adenosine triphosphatase) (EC 3.6.1.3) and associated K-+-dependent phosphatase activity (EC 3.6.1.7) have been compared. Unlike the (Na-++K-+)-dependent ATPase activities, the K-+-dependent phosphatase activities of a number of different preparations were not closely correlated with their total phospholipid contents. After partial lipid depletion with a single extraction in Lubrol W the residual ATPase and phosphatase activities were correlated, but their magnitudes were quite different: on average only about 5% of the former remained compared with 50% of the latter. A similar differential effect on these activities was found after extraction with deoxycholate. In contrast with the ATPase, consistent restoration of the phosphatase activity of Lubrol-extracted enzymes by added exogenous phospholipids was not observed. We conclude that, although the K-+-dependent phosphatase may be lipid-dependent, the lipid requirement must be different from that of the complete ATPase system, and this difference should help investigations of their relationship."} {"id": "PMID:167792", "title": "[Anti-inflammatory activity of a new quinoid polyradical (FL-70)].", "content": "The anti-inflammatory activity of FL 70, a derivative of 2,5-dihydroxy-benzoic acid, was examined in a number of conventional experimental models. In addition, FL-70 was tested for its inhibitory action on enzymes. The results were as follows: 1. The induction of a local inflammatory reaction and the subsequent i.v. injection of trypan blue showed that FL 70 reduces the capillary permeability. 2, FL-70 significantly suppresses exudation in the formalin-induced peritonitis of the rat. 3. A slight inhibition of an edema in the footpad of the rat induced by formalin-dextran was not shown to be statistically significant. 4. Local swelling could be markedly inhibited in the turpentine-oil induced inflammatory reaction of the rabbit. 5. Exudation and formation of granulomatous tissue was inhibited in Selye's granuloma. 6. FL-70 markedly inhibited the local inflammatory reaction accompanying the cutaneous reaction in experimental vaccinia infection of the rabbit skin. The size of the infiltration after intracutaneous infection of the virus was not reduced. 7. FL-70 could not prevent the onset of clinical signs, if administered in experimental allergic encephalitis. 8. The activity of acid phosphatase was inhibited by FL-70. Alcaline phosphatase, cholinesterase, leucin aminopeptidase, glucose-6- phosphatase-dehydrogenase (G-6-PDH), trypsin and chymotrypsin were unaffe-ted. FL-70 inhibits the following, G-6-PDH activated reduction process: glucose-6-phosphate (see article).", "contents": "[Anti-inflammatory activity of a new quinoid polyradical (FL-70)]. The anti-inflammatory activity of FL 70, a derivative of 2,5-dihydroxy-benzoic acid, was examined in a number of conventional experimental models. In addition, FL-70 was tested for its inhibitory action on enzymes. The results were as follows: 1. The induction of a local inflammatory reaction and the subsequent i.v. injection of trypan blue showed that FL 70 reduces the capillary permeability. 2, FL-70 significantly suppresses exudation in the formalin-induced peritonitis of the rat. 3. A slight inhibition of an edema in the footpad of the rat induced by formalin-dextran was not shown to be statistically significant. 4. Local swelling could be markedly inhibited in the turpentine-oil induced inflammatory reaction of the rabbit. 5. Exudation and formation of granulomatous tissue was inhibited in Selye's granuloma. 6. FL-70 markedly inhibited the local inflammatory reaction accompanying the cutaneous reaction in experimental vaccinia infection of the rabbit skin. The size of the infiltration after intracutaneous infection of the virus was not reduced. 7. FL-70 could not prevent the onset of clinical signs, if administered in experimental allergic encephalitis. 8. The activity of acid phosphatase was inhibited by FL-70. Alcaline phosphatase, cholinesterase, leucin aminopeptidase, glucose-6- phosphatase-dehydrogenase (G-6-PDH), trypsin and chymotrypsin were unaffe-ted. FL-70 inhibits the following, G-6-PDH activated reduction process: glucose-6-phosphate (see article)."} {"id": "PMID:167793", "title": "Snythesis and antiprotozoal activity of nitro derivatives of 2, 2'-biimidazole.", "content": "We synthesized a series of 2,2'-biimidazoles with different substituents and screened them against Entamoeba histolytica, Trichomonas vaginalis and Giardia muris. A 5-nitro group is necessary for the inclusion of activity and an amino group exercises favourable effect on in vivi activity.", "contents": "Snythesis and antiprotozoal activity of nitro derivatives of 2, 2'-biimidazole. We synthesized a series of 2,2'-biimidazoles with different substituents and screened them against Entamoeba histolytica, Trichomonas vaginalis and Giardia muris. A 5-nitro group is necessary for the inclusion of activity and an amino group exercises favourable effect on in vivi activity."} {"id": "PMID:167796", "title": "A search for microtubular inclusions in endothelial cells in a variety of skin diseases.", "content": "An electron microscopic study of a variety of skin diseases has demonstrated microtubular 'inclusions' in vascular endothelium in bullous pemphigoid for the first time. The 'inclusions' are similar to those originally reported in lupus erythematosus by Fresco (1968) and presently being detected in an increasing number and variety of pathological processes.", "contents": "A search for microtubular inclusions in endothelial cells in a variety of skin diseases. An electron microscopic study of a variety of skin diseases has demonstrated microtubular 'inclusions' in vascular endothelium in bullous pemphigoid for the first time. The 'inclusions' are similar to those originally reported in lupus erythematosus by Fresco (1968) and presently being detected in an increasing number and variety of pathological processes."} {"id": "PMID:167797", "title": "Micro-determination of cyclic AMP levels in human epidermis, dermis and haif follicles.", "content": "In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.", "contents": "Micro-determination of cyclic AMP levels in human epidermis, dermis and haif follicles. In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin."} {"id": "PMID:167798", "title": "Cyclic AMP in skin: effects of acute ischaemia.", "content": "The cyclic adenosine 3',5'-monophosphate (cyclic AMP) content of pig skin was measured several seconds to minutes after removal of the skin from the body. It increased very rapidly, reached a maximum by 2 min after removal (4 times higher than the initial level), then decreased very slowly. Propranolol injected into the animal before or added after the removal of the skin did not suppress this phenomenon. The practical significance of this finding (increase of cyclic AMP level in skin after ischaemia) is obvious-in order to measure cyclic AMP level in vivo, the sample must be frozen immediately to avoid an 'artificial' increase in cyclic AMP.", "contents": "Cyclic AMP in skin: effects of acute ischaemia. The cyclic adenosine 3',5'-monophosphate (cyclic AMP) content of pig skin was measured several seconds to minutes after removal of the skin from the body. It increased very rapidly, reached a maximum by 2 min after removal (4 times higher than the initial level), then decreased very slowly. Propranolol injected into the animal before or added after the removal of the skin did not suppress this phenomenon. The practical significance of this finding (increase of cyclic AMP level in skin after ischaemia) is obvious-in order to measure cyclic AMP level in vivo, the sample must be frozen immediately to avoid an 'artificial' increase in cyclic AMP."} {"id": "PMID:167799", "title": "Further studies on adenyl cyclase in psoriasis.", "content": "Slices of human skin obtained with a keratome were pre-incubated with [3H]adenine to label the ATP pool from which cyclic AMP was subsequently formed. The accumulation of radioactive cyclic AMP was measured as an index of adenyl cyclase activity. The data showed that both the ability to incorporate [3H] into ATP and adenyl cyclase activity were significantly lower in psoriatic plaques than in uninvolved skin of the psoriatic patients, or in normal skin of control subjects. The response of adenyl cyclase to the stimulation of 3.3 muM adrenaline was less than five fold in psoriatic plaques as compared to twelve to thirty-two fold in the uninvolved skin. The response to the stimulation of prostaglandin E2 (5 mug/ml) showed no significant difference between the plaque and normal skin. The adenyl cyclase activity in uninvolved skin of psoriatic patients appeared normal. Propranolol (10 muM) blocked the stimulatory effect of adrenaline but not that of PGE2 in normal skin. These results suggest that the adenyl cyclase system of the skin has different regulatory sites for adrenaline and PGE2 and that the enzyme is defective in the epidermis of the psoriatic plaque, especially at the adrenaline regulatory site.", "contents": "Further studies on adenyl cyclase in psoriasis. Slices of human skin obtained with a keratome were pre-incubated with [3H]adenine to label the ATP pool from which cyclic AMP was subsequently formed. The accumulation of radioactive cyclic AMP was measured as an index of adenyl cyclase activity. The data showed that both the ability to incorporate [3H] into ATP and adenyl cyclase activity were significantly lower in psoriatic plaques than in uninvolved skin of the psoriatic patients, or in normal skin of control subjects. The response of adenyl cyclase to the stimulation of 3.3 muM adrenaline was less than five fold in psoriatic plaques as compared to twelve to thirty-two fold in the uninvolved skin. The response to the stimulation of prostaglandin E2 (5 mug/ml) showed no significant difference between the plaque and normal skin. The adenyl cyclase activity in uninvolved skin of psoriatic patients appeared normal. Propranolol (10 muM) blocked the stimulatory effect of adrenaline but not that of PGE2 in normal skin. These results suggest that the adenyl cyclase system of the skin has different regulatory sites for adrenaline and PGE2 and that the enzyme is defective in the epidermis of the psoriatic plaque, especially at the adrenaline regulatory site."} {"id": "PMID:167800", "title": "Effect of dietary copper deficiency. in the rat on fatty acid composition of adipose tissue and desaturase activity of liver microsomes.", "content": "1. Male rats were maintained from wearing to between 4 and 16 weeks of age on a semisynthetic diet which was deficient in copper. 2. Methyl esters of fatty acids from adipose tissue of the rats were analysed by gas-liquid chromatography and the desaturase activity of liver microsomes, with [1-14C]=stearic acid as the substrate, was determined. Liver and plasma Cu concentration, cytohrome c oxidas (EC 1.9.3.I) activity and caeruloplasmin activity were determined as indices of Cu status. 3. Cu deficiency was associated with decreased mono-unsaturated:saturated ratios for C16 and C18 fatty acids from subcutaneous adipose tissue and decreased desaturase activity for liver microsomes. When Cu-deficient rats were given free access to the Cu-adequate diet or were injected intraperitoneally with an aqueous solution of CuSO4, that is, when the animals were related with Cu, the indices of Cu status, and desaturase activity for liver microsomes returned to values found in control animals. 4. When Cu or a Cu-chelator (Neocuproine) was added to microsomes, there was no effect on the activity of the desaturase enzyme system; the stability of the desaturase was not affected by Cu. 5. These results are indicative of an involvement of Cu in the desaturase reaction. It is suggested that the site of this involvement could be the terminal component of the microsomal electron transport chain.", "contents": "Effect of dietary copper deficiency. in the rat on fatty acid composition of adipose tissue and desaturase activity of liver microsomes. 1. Male rats were maintained from wearing to between 4 and 16 weeks of age on a semisynthetic diet which was deficient in copper. 2. Methyl esters of fatty acids from adipose tissue of the rats were analysed by gas-liquid chromatography and the desaturase activity of liver microsomes, with [1-14C]=stearic acid as the substrate, was determined. Liver and plasma Cu concentration, cytohrome c oxidas (EC 1.9.3.I) activity and caeruloplasmin activity were determined as indices of Cu status. 3. Cu deficiency was associated with decreased mono-unsaturated:saturated ratios for C16 and C18 fatty acids from subcutaneous adipose tissue and decreased desaturase activity for liver microsomes. When Cu-deficient rats were given free access to the Cu-adequate diet or were injected intraperitoneally with an aqueous solution of CuSO4, that is, when the animals were related with Cu, the indices of Cu status, and desaturase activity for liver microsomes returned to values found in control animals. 4. When Cu or a Cu-chelator (Neocuproine) was added to microsomes, there was no effect on the activity of the desaturase enzyme system; the stability of the desaturase was not affected by Cu. 5. These results are indicative of an involvement of Cu in the desaturase reaction. It is suggested that the site of this involvement could be the terminal component of the microsomal electron transport chain."} {"id": "PMID:167801", "title": "The action of colicin E2 on supercoiled lambda DNA.II. Experiments in vitro.", "content": "An in vitro system has been developed to test whether colicin E2 possesses DNase activity. Purified colicin E2 preparations introduced one single-strand scission in supercoiled lambda phage DNA. Glycerol gradient fractionation of colicin E2 supports the association of in vitro action with in vivo cell-killing activity. Colicin E2 preparations also attacked superhelical SV40 DNA yielding open circles and fragments and single-stranded fd DNA molecules causing one or more endonucleolytic breaks. The possible role of contaminating nucleases in the activity of colicin E2 preparations is discussed.", "contents": "The action of colicin E2 on supercoiled lambda DNA.II. Experiments in vitro. An in vitro system has been developed to test whether colicin E2 possesses DNase activity. Purified colicin E2 preparations introduced one single-strand scission in supercoiled lambda phage DNA. Glycerol gradient fractionation of colicin E2 supports the association of in vitro action with in vivo cell-killing activity. Colicin E2 preparations also attacked superhelical SV40 DNA yielding open circles and fragments and single-stranded fd DNA molecules causing one or more endonucleolytic breaks. The possible role of contaminating nucleases in the activity of colicin E2 preparations is discussed."} {"id": "PMID:167802", "title": "Spin-label studies of tropomyosin.", "content": "Studies are reported on nitroxide spin-labeled tropomyosin. The labels attach to sulfhydryl groups and to amino groups. The amino spins are highly mobile, the sulfhydryl much less so. Spin count studies show an average of approximately 0.5 labeled sulfhydryl/tropomyosin molecule and only approximately 0.15 labeled amino group/molecule. The spectra are used tostudy the denaturation of tropomyosin by guanidine hydrochloride. The information obtained reveals the course of denaturation at sites near the sulfhydryl group. It is found that these sites are more susceptible to guanidine than the bulk of the molecule; denaturation at the sulfhydryl sites is complete by 1.5 M guanidine, whereas optical studies indicate the molecule as a whole is not completely denatured until the concentration reaches 3.5 M. Spectra are also shown of tropomyosin fibers oriented variously with respect to the applied magnetic field. Strong orientation effects are seen and these indicate that the sulfhydryl-attached spins (but not the amino-attached spins) have a definite orientation in the fiber. Interpretation of the spectra reveals that the normal to the nitroxide plane is inclined to the fiber axis at an angle of 50 degrees. Circular dichroism studies in the tyrosine region also reveal drastic changes with guanidine denaturation, confirming the idea that denaturation produces pronounced increase in mobility at the beta carbon (as in the sulfhydryl casey). A strong negative band existing only in helical tropomyosin at pH's where the tyrosines are uncharged appears to be due to interaction of tyrosines with the helical backbone, whereas the appearance of a strong positive CD band at 250 nm at high pH (approximately11) seems to be ascribable to interaction between the charged phenolic groups and the dissymmetric backbone alpha-carbon atom.", "contents": "Spin-label studies of tropomyosin. Studies are reported on nitroxide spin-labeled tropomyosin. The labels attach to sulfhydryl groups and to amino groups. The amino spins are highly mobile, the sulfhydryl much less so. Spin count studies show an average of approximately 0.5 labeled sulfhydryl/tropomyosin molecule and only approximately 0.15 labeled amino group/molecule. The spectra are used tostudy the denaturation of tropomyosin by guanidine hydrochloride. The information obtained reveals the course of denaturation at sites near the sulfhydryl group. It is found that these sites are more susceptible to guanidine than the bulk of the molecule; denaturation at the sulfhydryl sites is complete by 1.5 M guanidine, whereas optical studies indicate the molecule as a whole is not completely denatured until the concentration reaches 3.5 M. Spectra are also shown of tropomyosin fibers oriented variously with respect to the applied magnetic field. Strong orientation effects are seen and these indicate that the sulfhydryl-attached spins (but not the amino-attached spins) have a definite orientation in the fiber. Interpretation of the spectra reveals that the normal to the nitroxide plane is inclined to the fiber axis at an angle of 50 degrees. Circular dichroism studies in the tyrosine region also reveal drastic changes with guanidine denaturation, confirming the idea that denaturation produces pronounced increase in mobility at the beta carbon (as in the sulfhydryl casey). A strong negative band existing only in helical tropomyosin at pH's where the tyrosines are uncharged appears to be due to interaction of tyrosines with the helical backbone, whereas the appearance of a strong positive CD band at 250 nm at high pH (approximately11) seems to be ascribable to interaction between the charged phenolic groups and the dissymmetric backbone alpha-carbon atom."} {"id": "PMID:167803", "title": "Correlation between quaternary structure and ligand dissociation kinetics for fully liganded hemoglobin.", "content": "The quaternary structures of fully liganded adult hemoglobin and hemoglobin Kansas (alpha2beta2 102 Asn-thr) bound by carbon monoxide or nitric oxide were spectroscopically characterized using high-resolution nuclear magnetic resonance (NMR) and ultraviolet circular dichroism (CD). The spectral markers used for the quarternary transition were the line in the NMR spectrum in H2O-14 ppm downfield from 2,2-dimethyl-2-silapentane-5-sulfonate and the negative peak at 285 nm in the ultraviolet CD spectrum. In the nitrosyl derivatives, these two structural markers were compared with the electron paramagnetic resonance (EPR) spectrum at room temperature for the purpose of correlating structural changes in the protein with changes at the heme...", "contents": "Correlation between quaternary structure and ligand dissociation kinetics for fully liganded hemoglobin. The quaternary structures of fully liganded adult hemoglobin and hemoglobin Kansas (alpha2beta2 102 Asn-thr) bound by carbon monoxide or nitric oxide were spectroscopically characterized using high-resolution nuclear magnetic resonance (NMR) and ultraviolet circular dichroism (CD). The spectral markers used for the quarternary transition were the line in the NMR spectrum in H2O-14 ppm downfield from 2,2-dimethyl-2-silapentane-5-sulfonate and the negative peak at 285 nm in the ultraviolet CD spectrum. In the nitrosyl derivatives, these two structural markers were compared with the electron paramagnetic resonance (EPR) spectrum at room temperature for the purpose of correlating structural changes in the protein with changes at the heme..."} {"id": "PMID:167804", "title": "Mapping of the SV40 specific sequences transcribed in vitro from chromatin of SV40 transformed cells.", "content": "Chromatin was isolated from SV40 transformed mouse cells (SV3T3) and transcribed with Escherichia coli RNA polymerase. The SV40 specific transcripts were analyzed by annealing the RNA to the minus strands of purified fragments of SV40 DNA produced by cleavage of the DNA with a restriction enzyme isolated from Hemophilus aegyptius. Quantitation of the frequency of transcription from the region (fragments A and D) was transcribed five to ten times more frequently than the remaining regions. These results are in good agreement with the transcription pattern observed in the transformed cell. In contrast, transcription of purified SV3T3 DNA by E. coli polymerase produced roughly equal frequencies of transcription from all regions of the integrated SV40 DNA. Comparison of the results with the known distribution of initiation sites for E. coli RNA polymerase on linear SV40 DNA indicates that the major initiation site is relatively unavailable in SV3T3 chromatin whereas other sites are available. This restriction is not observed when purified SV3T3 DNA is used as a template and must therefore result from the association of protein or other macromolecules with the DNA of the chromatin.", "contents": "Mapping of the SV40 specific sequences transcribed in vitro from chromatin of SV40 transformed cells. Chromatin was isolated from SV40 transformed mouse cells (SV3T3) and transcribed with Escherichia coli RNA polymerase. The SV40 specific transcripts were analyzed by annealing the RNA to the minus strands of purified fragments of SV40 DNA produced by cleavage of the DNA with a restriction enzyme isolated from Hemophilus aegyptius. Quantitation of the frequency of transcription from the region (fragments A and D) was transcribed five to ten times more frequently than the remaining regions. These results are in good agreement with the transcription pattern observed in the transformed cell. In contrast, transcription of purified SV3T3 DNA by E. coli polymerase produced roughly equal frequencies of transcription from all regions of the integrated SV40 DNA. Comparison of the results with the known distribution of initiation sites for E. coli RNA polymerase on linear SV40 DNA indicates that the major initiation site is relatively unavailable in SV3T3 chromatin whereas other sites are available. This restriction is not observed when purified SV3T3 DNA is used as a template and must therefore result from the association of protein or other macromolecules with the DNA of the chromatin."} {"id": "PMID:167805", "title": "Initial membrane reaction in the biosynthesis of peptidoglycan. Spin-labeled intermediates as receptors for vancomycin and ristocetin.", "content": "Phospho-N-acetylmuramyl-pentapeptide translocase (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla:undecaprenyl phosphate, phospho-MurNAc-pentapeptide transferase) catalyzes the initial membrane reaction in the biosynthesis of peptidoglycan. The spin-labeled nucleotide, UDP-MurNAc-Ala-DGlu-Lys (Nepsilon-2,2,5,5-tetramethyl-N-oxyl-pyrroline-3-carbonyl)-DAla-DAla, was used as a substrate by this enzyme for the synthesis of membrane-associated undecaprenyl-diphosphate-MurNAc-Ala-DGlu-Lys(Nepsilon-Tempyo)-DAla-DAla. The spin-labeled substrate and product complex with the antibiotics vancomycin and ristocetin. The association constants for the spin-labeled nucleotide are 6.2 times 10(5) and 6.2 times 10(4) M-1 for vancomycin and ristocetin, respectively. The association constants for the spin-labeled lipid intermediate are 3.0 times 10(4) and 2.1 times 10(4) M-1 for vancomycin and ristocetin, respectively. These results indicate that the acyl-DAla termini of membranes-associated spin-labeled undecaprenyl-diphosphate-MurNAc-pentapeptide are accessible to vancomycin and ristocetin and that the association constants are smaller than those determined for the corresponding antibiotic spin-labeled UDP-MurNAc-pentapeptide complexes.", "contents": "Initial membrane reaction in the biosynthesis of peptidoglycan. Spin-labeled intermediates as receptors for vancomycin and ristocetin. Phospho-N-acetylmuramyl-pentapeptide translocase (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla:undecaprenyl phosphate, phospho-MurNAc-pentapeptide transferase) catalyzes the initial membrane reaction in the biosynthesis of peptidoglycan. The spin-labeled nucleotide, UDP-MurNAc-Ala-DGlu-Lys (Nepsilon-2,2,5,5-tetramethyl-N-oxyl-pyrroline-3-carbonyl)-DAla-DAla, was used as a substrate by this enzyme for the synthesis of membrane-associated undecaprenyl-diphosphate-MurNAc-Ala-DGlu-Lys(Nepsilon-Tempyo)-DAla-DAla. The spin-labeled substrate and product complex with the antibiotics vancomycin and ristocetin. The association constants for the spin-labeled nucleotide are 6.2 times 10(5) and 6.2 times 10(4) M-1 for vancomycin and ristocetin, respectively. The association constants for the spin-labeled lipid intermediate are 3.0 times 10(4) and 2.1 times 10(4) M-1 for vancomycin and ristocetin, respectively. These results indicate that the acyl-DAla termini of membranes-associated spin-labeled undecaprenyl-diphosphate-MurNAc-pentapeptide are accessible to vancomycin and ristocetin and that the association constants are smaller than those determined for the corresponding antibiotic spin-labeled UDP-MurNAc-pentapeptide complexes."} {"id": "PMID:167806", "title": "A link between rhodopsin and disc membrane cyclic nucleotide phosphodiesterase. Action spectrum and sensitivity to illumination.", "content": "Frog (Rana pipiens) rod outer segment disc membranes contain guanosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.1.c) which, in the presence of ATP, is stimulated 5- to 20-fold by illumination. The effectiveness of monochromatic light of different wavelengths in activating phosphodiesterase was examined. The action spectrum has a maximum of 500 nm, and the entire spectrum from 350 to 800 nm closely matches the absorption spectrum of rhodopsin, which is apparently the pigment which mediates the effects of light on phosphodiesterase activity. trans-Retinal alone does not mimic light. Half-maximal activation of the phosphodiesterase occurs with a light exposure which bleaches 1/2000 of the rhodopsins. Half-maximal activation can also be achieved by mixing 1 part of illuminated disc membranes in which the rhodopsin is bleached with 99 parts of unilluminated membranes. Regeneration of bleached rhodopsin by addition of 11-cis-retinal is illuminated disc membranes reverses the ability of these membranes to activate phosphodiesterase in unilluminated membranes. If the rhodopsin regenerated by 11-cis-retinal is illuminated again, it regains the ability to activate phosphodiesterase. These studies show that the levels of cyclic nucleotides in vetebrate rod outer segments are regulated by minute amounts of light and clearly indicate that rhodopsin is the photopigment whose state of illumination is closely linked to the enzymatic activity of disc membrane phosphodiesterase.", "contents": "A link between rhodopsin and disc membrane cyclic nucleotide phosphodiesterase. Action spectrum and sensitivity to illumination. Frog (Rana pipiens) rod outer segment disc membranes contain guanosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.1.c) which, in the presence of ATP, is stimulated 5- to 20-fold by illumination. The effectiveness of monochromatic light of different wavelengths in activating phosphodiesterase was examined. The action spectrum has a maximum of 500 nm, and the entire spectrum from 350 to 800 nm closely matches the absorption spectrum of rhodopsin, which is apparently the pigment which mediates the effects of light on phosphodiesterase activity. trans-Retinal alone does not mimic light. Half-maximal activation of the phosphodiesterase occurs with a light exposure which bleaches 1/2000 of the rhodopsins. Half-maximal activation can also be achieved by mixing 1 part of illuminated disc membranes in which the rhodopsin is bleached with 99 parts of unilluminated membranes. Regeneration of bleached rhodopsin by addition of 11-cis-retinal is illuminated disc membranes reverses the ability of these membranes to activate phosphodiesterase in unilluminated membranes. If the rhodopsin regenerated by 11-cis-retinal is illuminated again, it regains the ability to activate phosphodiesterase. These studies show that the levels of cyclic nucleotides in vetebrate rod outer segments are regulated by minute amounts of light and clearly indicate that rhodopsin is the photopigment whose state of illumination is closely linked to the enzymatic activity of disc membrane phosphodiesterase."} {"id": "PMID:167807", "title": "Regulation of Membrane Flexibility in Human Erythrocytes.", "content": "We have used spin-labels to detect prostaglandin E induced changes in erythrocyte membranes. The observed changes in spin-label resonance spectra can be mimicked in erythrocyte ghosts by loading them with cAMP or cGMP. These changes can also be observed by adding either of these cyclic nucleotides to intact cells. This entry of cyclic nucleotides into intact cells is blocked by an inhibitor of the anion channel. We suggest that the observed changes in paramagnetic resonance spectra are due to changes in lipid \"fluidity\" that are brought about by changes in the biochemical state of membrane-associated proteins (such as spectrin) and in the direct or indirect biophysical interactions of these proteins with membrane lipids.", "contents": "Regulation of Membrane Flexibility in Human Erythrocytes. We have used spin-labels to detect prostaglandin E induced changes in erythrocyte membranes. The observed changes in spin-label resonance spectra can be mimicked in erythrocyte ghosts by loading them with cAMP or cGMP. These changes can also be observed by adding either of these cyclic nucleotides to intact cells. This entry of cyclic nucleotides into intact cells is blocked by an inhibitor of the anion channel. We suggest that the observed changes in paramagnetic resonance spectra are due to changes in lipid \"fluidity\" that are brought about by changes in the biochemical state of membrane-associated proteins (such as spectrin) and in the direct or indirect biophysical interactions of these proteins with membrane lipids."} {"id": "PMID:167808", "title": "Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding.", "content": "Cholesterol feeding in miniature swine resulted in a hypercholesterolemia with a distinctive hyperlipoproteinemia and the subsequent development of atherosclerosis. Alterations in the type and distribution of plasma lipoproteins induced by cholesterol feeding were as follows: (a) the occurrence of beta-migrating lipoproteins (B-VLDL) as well as very low density lipoproteins in the d less than 1.006 ultracentrifugal fraction; (b) an increased prominence of the intermediate lipoproteins (d = 1.006-1.02); (c) an increased prominence of low density lipoproteins; and (d) the occurrence of a distinctive lipoprotein with alpha mobility which was referred to as HDLc (cholesterol induced). Characterization of the various plasma lipoproteins included chemical composition, size by electron microscopy, and apoprotein content. The B-VLDL resembled the beta-migrating lipoproteins of human Type III hyperlipoproteinemia and contained a prominent protein equivalent to the arginine-rich apoprotein in addition to the B apoprotein, apo-A-I, and the fast-migrating apoproteins (apo-C). The HDLc were rich in cholesterol, ranged in size from 100 to 240 A in diameter, and contained the arginine-rich apoprotein and apo-A0I but lacked the B apoprotein. The arginine-rich apoproteins isolated from B-VLDL and HDLc by gel chromatography were similar in amino acid analyses, with glutamic acid as their amino-terminal residue. The occurrence of a spectrum of cholesterol-rich lipoproteins which contained the arginine-rich apoprotein with the occurrence of accelerated atherosclerosis suggested an interesting, although speculative, association.", "contents": "Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding. Cholesterol feeding in miniature swine resulted in a hypercholesterolemia with a distinctive hyperlipoproteinemia and the subsequent development of atherosclerosis. Alterations in the type and distribution of plasma lipoproteins induced by cholesterol feeding were as follows: (a) the occurrence of beta-migrating lipoproteins (B-VLDL) as well as very low density lipoproteins in the d less than 1.006 ultracentrifugal fraction; (b) an increased prominence of the intermediate lipoproteins (d = 1.006-1.02); (c) an increased prominence of low density lipoproteins; and (d) the occurrence of a distinctive lipoprotein with alpha mobility which was referred to as HDLc (cholesterol induced). Characterization of the various plasma lipoproteins included chemical composition, size by electron microscopy, and apoprotein content. The B-VLDL resembled the beta-migrating lipoproteins of human Type III hyperlipoproteinemia and contained a prominent protein equivalent to the arginine-rich apoprotein in addition to the B apoprotein, apo-A-I, and the fast-migrating apoproteins (apo-C). The HDLc were rich in cholesterol, ranged in size from 100 to 240 A in diameter, and contained the arginine-rich apoprotein and apo-A0I but lacked the B apoprotein. The arginine-rich apoproteins isolated from B-VLDL and HDLc by gel chromatography were similar in amino acid analyses, with glutamic acid as their amino-terminal residue. The occurrence of a spectrum of cholesterol-rich lipoproteins which contained the arginine-rich apoprotein with the occurrence of accelerated atherosclerosis suggested an interesting, although speculative, association."} {"id": "PMID:167809", "title": "13-C nuclear magnetic resonance studies on the lipid organization in enveloped virions (vesicular stomatitis virus).", "content": "13-C nuclear magnetic resonance (NMR) studies are described regarding the lipid organization in the envelope of the vesicular stomatitis virion. The fatty acid chains (oleic acid) and the choline moiety of the 3-sn-phosphatidylcholine and spingomyelin have been labeled specifically with 13-C by growing the virions in prelabeled host cells (BHK 21 cells). The results suggest that 130C NMR spectroscopy is a very feasible method for the study of natural membranes provided the isotope is highly enriched in specific positions and incorporated biochemically. Spin-lattice relaxation (T1) measurements of particular C atoms have been carried out with whole virions, with virions deprived of their surface projections by trypsinization but unaltered in their shape and size, and with liposomes prepared from the total lipid mixture of the envelope in order to get insight into the molecular structure of this model membrane. The mobility of the central part of 11-13-C-labeled oleic acid incorporated into the ester and amide lipids and the choline group of 3-sn-phosphatidylcholine and sphingomyelin is very restricted as indicated by their short T1 times. It is concluded from the data presented here that the high cholesterol content (cholesterol/P: 0.7) of the envelope lipid phase is responsible for the rather rigidly packed envelope structure. The mode and extent of the interactions between lipids and glycoprotein surface projections are subjects for further study.", "contents": "13-C nuclear magnetic resonance studies on the lipid organization in enveloped virions (vesicular stomatitis virus). 13-C nuclear magnetic resonance (NMR) studies are described regarding the lipid organization in the envelope of the vesicular stomatitis virion. The fatty acid chains (oleic acid) and the choline moiety of the 3-sn-phosphatidylcholine and spingomyelin have been labeled specifically with 13-C by growing the virions in prelabeled host cells (BHK 21 cells). The results suggest that 130C NMR spectroscopy is a very feasible method for the study of natural membranes provided the isotope is highly enriched in specific positions and incorporated biochemically. Spin-lattice relaxation (T1) measurements of particular C atoms have been carried out with whole virions, with virions deprived of their surface projections by trypsinization but unaltered in their shape and size, and with liposomes prepared from the total lipid mixture of the envelope in order to get insight into the molecular structure of this model membrane. The mobility of the central part of 11-13-C-labeled oleic acid incorporated into the ester and amide lipids and the choline group of 3-sn-phosphatidylcholine and sphingomyelin is very restricted as indicated by their short T1 times. It is concluded from the data presented here that the high cholesterol content (cholesterol/P: 0.7) of the envelope lipid phase is responsible for the rather rigidly packed envelope structure. The mode and extent of the interactions between lipids and glycoprotein surface projections are subjects for further study."} {"id": "PMID:167810", "title": "The amino acid sequence of chick skin collagen alpha1-CB7.", "content": "The amino acid sequence of chick skin collagen alpha1-CB7, the 268 CNBr peptide from the helical portion of the alpha1 chain, has been determined by automatic and manual degradation of tryptic and chymotryptic peptides, and of the COOH-terminal fragment produced by cleavage with animal collagenase. The resulting sequence shows 94% identity with that of the corresponding peptide from calf skin collage (Fietzek, P. P., Rexrodt, F. W., Hopper, K. E., and K\u00fchn, K. (1973), Eur. J. Biochem. 38, 396). The bond cleaved by animal collagenase has been identified as Gly-Ile at residues 221-222 of alpha1-CB7.", "contents": "The amino acid sequence of chick skin collagen alpha1-CB7. The amino acid sequence of chick skin collagen alpha1-CB7, the 268 CNBr peptide from the helical portion of the alpha1 chain, has been determined by automatic and manual degradation of tryptic and chymotryptic peptides, and of the COOH-terminal fragment produced by cleavage with animal collagenase. The resulting sequence shows 94% identity with that of the corresponding peptide from calf skin collage (Fietzek, P. P., Rexrodt, F. W., Hopper, K. E., and K\u00fchn, K. (1973), Eur. J. Biochem. 38, 396). The bond cleaved by animal collagenase has been identified as Gly-Ile at residues 221-222 of alpha1-CB7."} {"id": "PMID:167811", "title": "Adrenocorticotropic hormone stimulation of adrenal RNA polymerase I and III activities. Nucleotide incorporation into internal positions and 3' chain termini.", "content": "In the presence of 50 mM (NH4)2SO4 and low concentrations of alpha-amanitin (7.7 mug/ml), adrenal nuclei synthesize predominately rRNA as characterized by size and base composition. Approximately 10% of the RNA synthesized under these conditions sediments at 4-5 S; this RNA synthesizing activity is inhibited by high concentrations of alpha-amanitin (231 mug/ml) indicating the presence of RNA polymerase III activity. ACTH administration to guinea pigs results in a twofold increase in adrenal nuclear RNA polymerase I and III activities at 14 hr of hormone treatment. Analysis of the amount of radiolabeled nucleoside triphosphate incorporated in vitro into 3' chain termini and into internal nucleotide positions has been utilized to measure the number of RNA chains and the average chain length synthesized in vitro. Incorporation into 3' chain termini is not changed by ACTH; incorporation into internal nucleotides is doubled in parallel with the increase in RNA polymerase I activity. These results are not due to an altered Km of RNA polymerase I for the four nucleoside triphosphates, nor to differential R Nase or phosphatase activity. These studies suggest that the regulation of RNA polymerase I by ACTH is accomplished in part through an increase in the rate of RNA chain elongation.", "contents": "Adrenocorticotropic hormone stimulation of adrenal RNA polymerase I and III activities. Nucleotide incorporation into internal positions and 3' chain termini. In the presence of 50 mM (NH4)2SO4 and low concentrations of alpha-amanitin (7.7 mug/ml), adrenal nuclei synthesize predominately rRNA as characterized by size and base composition. Approximately 10% of the RNA synthesized under these conditions sediments at 4-5 S; this RNA synthesizing activity is inhibited by high concentrations of alpha-amanitin (231 mug/ml) indicating the presence of RNA polymerase III activity. ACTH administration to guinea pigs results in a twofold increase in adrenal nuclear RNA polymerase I and III activities at 14 hr of hormone treatment. Analysis of the amount of radiolabeled nucleoside triphosphate incorporated in vitro into 3' chain termini and into internal nucleotide positions has been utilized to measure the number of RNA chains and the average chain length synthesized in vitro. Incorporation into 3' chain termini is not changed by ACTH; incorporation into internal nucleotides is doubled in parallel with the increase in RNA polymerase I activity. These results are not due to an altered Km of RNA polymerase I for the four nucleoside triphosphates, nor to differential R Nase or phosphatase activity. These studies suggest that the regulation of RNA polymerase I by ACTH is accomplished in part through an increase in the rate of RNA chain elongation."} {"id": "PMID:167812", "title": "Synthetic position 5 analogs of adrenocorticotropin fragments and their in vitro lipolytic activity.", "content": "Twenty-three analogs of the ACTH-(4-10)-heptapeptide sequence, which forms the \"active core\" of adrenocorticotropin (ACTH) and related hormones, have been synthesized by the solid-phase method. These analogs all contain structural modifications at or near the 5-glutamic acid residue of ACTH. The peptides were purified to electrophoretic and chromatographic homogeneity. The peptides were assayed for lipolytic activity in an isolated cell system derived from rabbit adipose tissue. In this system, it was determined that residue 5 plays a very important \"spacer\" role in the peptide, but that this spacer function is not very dependent on the nature of the side chain of the position 5 amino acid. It was found, however, that a number of analogs containing basic residues (arginine or lysine) in position 3 and/or position 5 of ACTH-(3-10) and ACTH-(4-10) fragments have 5 to 10 times the activity of the respective parent peptides. The presence of a latent anionic locus in the rabbit fat-cell receptor for ACTH is suggested by this study.", "contents": "Synthetic position 5 analogs of adrenocorticotropin fragments and their in vitro lipolytic activity. Twenty-three analogs of the ACTH-(4-10)-heptapeptide sequence, which forms the \"active core\" of adrenocorticotropin (ACTH) and related hormones, have been synthesized by the solid-phase method. These analogs all contain structural modifications at or near the 5-glutamic acid residue of ACTH. The peptides were purified to electrophoretic and chromatographic homogeneity. The peptides were assayed for lipolytic activity in an isolated cell system derived from rabbit adipose tissue. In this system, it was determined that residue 5 plays a very important \"spacer\" role in the peptide, but that this spacer function is not very dependent on the nature of the side chain of the position 5 amino acid. It was found, however, that a number of analogs containing basic residues (arginine or lysine) in position 3 and/or position 5 of ACTH-(3-10) and ACTH-(4-10) fragments have 5 to 10 times the activity of the respective parent peptides. The presence of a latent anionic locus in the rabbit fat-cell receptor for ACTH is suggested by this study."} {"id": "PMID:167813", "title": "Effect of the human plasma apolipoproteins and phosphatidylcholine acyl donor on the activity of lecithin: cholesterol acyltransferase.", "content": "The human plasma apoproteins apoA-I and apoC-I enhanced the activity of partially purified lecithin: cholesterol acyltransferase five to tenfold with chemically defined phosphatidylcholine:cholesterol single bilayer vesicles as substrates. By contrast, apoproteins apoA-II, apoC-II, and apoC-III did not give any enhancement of enzyme activity. The activation by apoA-I and apoC-I differed, depending upon the nature of the hydrocarbon chains of phosphatidylcholine acyl donor. ApoA-I was most effective with a phosphatidylcholine containing an unsaturated fatty acyl chain. ApoC-I activated LCAT to the same extent with both saturated and unsaturated phosphatidylcholine substrates. Two of the four peptides obtained by cyanogen bromide cleavage of apoA-I retained some ability to activate LCAT. The efficacy of each of these peptides was approximately 25% that of the whole protein. Cyanogen bromide fragments of apoC-I were inactive. The apoproteins from HDL, HDL2, and HDL3, at low protein concentrations, were equally effective as activators of LCATand less effective than apoA-I. Higher concentrations of apoHDL, apoHDL2, and apoHDL3 inhibited LCAT activity. ApoC and apoA-II were both found to inhibit the activation of LCAT by apoA-I. The inhibition of LCAT by higher concentrations of apoHDL was not correlated with the aopA-II and apoC content.", "contents": "Effect of the human plasma apolipoproteins and phosphatidylcholine acyl donor on the activity of lecithin: cholesterol acyltransferase. The human plasma apoproteins apoA-I and apoC-I enhanced the activity of partially purified lecithin: cholesterol acyltransferase five to tenfold with chemically defined phosphatidylcholine:cholesterol single bilayer vesicles as substrates. By contrast, apoproteins apoA-II, apoC-II, and apoC-III did not give any enhancement of enzyme activity. The activation by apoA-I and apoC-I differed, depending upon the nature of the hydrocarbon chains of phosphatidylcholine acyl donor. ApoA-I was most effective with a phosphatidylcholine containing an unsaturated fatty acyl chain. ApoC-I activated LCAT to the same extent with both saturated and unsaturated phosphatidylcholine substrates. Two of the four peptides obtained by cyanogen bromide cleavage of apoA-I retained some ability to activate LCAT. The efficacy of each of these peptides was approximately 25% that of the whole protein. Cyanogen bromide fragments of apoC-I were inactive. The apoproteins from HDL, HDL2, and HDL3, at low protein concentrations, were equally effective as activators of LCATand less effective than apoA-I. Higher concentrations of apoHDL, apoHDL2, and apoHDL3 inhibited LCAT activity. ApoC and apoA-II were both found to inhibit the activation of LCAT by apoA-I. The inhibition of LCAT by higher concentrations of apoHDL was not correlated with the aopA-II and apoC content."} {"id": "PMID:167814", "title": "Synthesis of a new phosphatidylserine spin-label and calcium-induced lateral phase separation in phosphatidylserine-phosphatidylcholine membranes.", "content": "A new phosphatidylserine spin label with nitroxide stearate attached at the 2 position has been synthesized by the reaction of spin-labeled CDP-diglyceride with L-serine under the catalytic action of phosphatidylserine synthetase. Some structural properties of pure phosphatidylserine (PS) and binary PS-phosphatidylcholine (PC) membranes were studied with the spin label. PS membrane became solidified on lowering solution pH, 50% solidification being attained at pH 3.5. The membrane was also solidified by addition of Ca-2+. The effect of Ba-2+,Sr-2+, and Mg-2+ was smaller than that of Ca-2+. The calcium-induced lateral phase separation in the binary membrane was studied from the side of the calcium-receiving lipid. The results confirmed and extended our previous conclusion drawn with PC spin label. The phase diagram of the binary membrane in the presence of Ca-2+ was determined. Not all PS molecules were aggregated to form the solid patches but some remained dissolved in the fluid PC matrix. The fluid PS fraction was larger for the membranes containing more PC. The membrane with 10% PS still had a significant fraction of solid phase. The rate of calcium-induced aggregation was greatly dependent on the PS content. The aggregation was almost complete within 5 min in the membrane containing 67% PS, while it was still proceeding after several hours in the membrane with 20% PS. The rate-limiting step was suggested to be in the formation of \"stable\" nuclei consisting of larger aggregates. The possible biological significance of the ionotropic phase separation was discussed whereby a transient density fluctuation was emphasized.", "contents": "Synthesis of a new phosphatidylserine spin-label and calcium-induced lateral phase separation in phosphatidylserine-phosphatidylcholine membranes. A new phosphatidylserine spin label with nitroxide stearate attached at the 2 position has been synthesized by the reaction of spin-labeled CDP-diglyceride with L-serine under the catalytic action of phosphatidylserine synthetase. Some structural properties of pure phosphatidylserine (PS) and binary PS-phosphatidylcholine (PC) membranes were studied with the spin label. PS membrane became solidified on lowering solution pH, 50% solidification being attained at pH 3.5. The membrane was also solidified by addition of Ca-2+. The effect of Ba-2+,Sr-2+, and Mg-2+ was smaller than that of Ca-2+. The calcium-induced lateral phase separation in the binary membrane was studied from the side of the calcium-receiving lipid. The results confirmed and extended our previous conclusion drawn with PC spin label. The phase diagram of the binary membrane in the presence of Ca-2+ was determined. Not all PS molecules were aggregated to form the solid patches but some remained dissolved in the fluid PC matrix. The fluid PS fraction was larger for the membranes containing more PC. The membrane with 10% PS still had a significant fraction of solid phase. The rate of calcium-induced aggregation was greatly dependent on the PS content. The aggregation was almost complete within 5 min in the membrane containing 67% PS, while it was still proceeding after several hours in the membrane with 20% PS. The rate-limiting step was suggested to be in the formation of \"stable\" nuclei consisting of larger aggregates. The possible biological significance of the ionotropic phase separation was discussed whereby a transient density fluctuation was emphasized."} {"id": "PMID:167815", "title": "Kinetics of gonadotropin binding by receptors of the rat testis. Analysis by a nonlinear curve-fitting method.", "content": "The kinetics of the reaction between human chorionic gonadotropin (hCG) and specific gonadotropin receptors in the rat testis were determined at 24 and 37 degrees, over a wide range of hormone concentrations. Hormone concentrations were corrected for the binding activity of the (-125I)hCG tracer preparations. Analysis of the experimental data was performed with an interactive nonlinear curve fitting program, based upon the second-order chemical kinetic differential equation. The mean values for the association rate constant (k1) were 4.7 x 10-7 M-1 min-1 at 24 degrees, and 11.0 x 10-7 M-1 min-1 at 37 degrees. At both temperatures, the values of kl were independent of hormone concentration. Initial dissociation rates were consistent with first order kinetics, with dissociation rate constant (k2) of 1.7 x 10 minus -3 and 4.6 x 10 minus -3 min minus -1 at 24 and 37 degrees, respectively. When studied over longer periods at 24 degrees, the dissociation process appeared to be multiexponential. The kinetics of degradation of (-125I)hCG and receptors were determined at both temperatures, and a mathematical model was developed by modification of the second-order chemical kinetic differential equation to take these factors into account. The application of such a model to hCG kinetic binding data demonstrated that reactant degradation had little significant effect on the derivation of the association rate constant (k1), but caused significant overestimation of the dissociation rate constant (k2) values derived from association experiments. The model was also applied by computer simulation to a theoretical analysis of the effects of degradation of free hormone and receptor sites upon kinetic and steadystate binding data. By this method, the initial velocities of hormone binding were shown to be less affected by degradation than the steady-state levels of hormone-receptor complex. Also, reactant degradation in simulated steady-state experiments caused an underestimate of the apparent equilibrium association constant, but had relatively less effect on the determination of binding site concentration.", "contents": "Kinetics of gonadotropin binding by receptors of the rat testis. Analysis by a nonlinear curve-fitting method. The kinetics of the reaction between human chorionic gonadotropin (hCG) and specific gonadotropin receptors in the rat testis were determined at 24 and 37 degrees, over a wide range of hormone concentrations. Hormone concentrations were corrected for the binding activity of the (-125I)hCG tracer preparations. Analysis of the experimental data was performed with an interactive nonlinear curve fitting program, based upon the second-order chemical kinetic differential equation. The mean values for the association rate constant (k1) were 4.7 x 10-7 M-1 min-1 at 24 degrees, and 11.0 x 10-7 M-1 min-1 at 37 degrees. At both temperatures, the values of kl were independent of hormone concentration. Initial dissociation rates were consistent with first order kinetics, with dissociation rate constant (k2) of 1.7 x 10 minus -3 and 4.6 x 10 minus -3 min minus -1 at 24 and 37 degrees, respectively. When studied over longer periods at 24 degrees, the dissociation process appeared to be multiexponential. The kinetics of degradation of (-125I)hCG and receptors were determined at both temperatures, and a mathematical model was developed by modification of the second-order chemical kinetic differential equation to take these factors into account. The application of such a model to hCG kinetic binding data demonstrated that reactant degradation had little significant effect on the derivation of the association rate constant (k1), but caused significant overestimation of the dissociation rate constant (k2) values derived from association experiments. The model was also applied by computer simulation to a theoretical analysis of the effects of degradation of free hormone and receptor sites upon kinetic and steadystate binding data. By this method, the initial velocities of hormone binding were shown to be less affected by degradation than the steady-state levels of hormone-receptor complex. Also, reactant degradation in simulated steady-state experiments caused an underestimate of the apparent equilibrium association constant, but had relatively less effect on the determination of binding site concentration."} {"id": "PMID:167816", "title": "Demonstration and partial characterization of cytosol receptors for testosterone.", "content": "Androgen uptake was investigated in several peripheral organs after administration of (1,2,6,7 minus -3H)testosterone to castrated male rats. The animals were killed after 30 min, the organs were taken out, and the radioactivity was determined after tissue combustion. A relatively high accumulation of androgen was found in pancreas, adrenals, spleen, thigh muscle, kidneys, and liver in addition to the classical androgen target organs coagulation glands, seminal vesicles, prostate, preputial glands, and harderian glands. In a second serier of experiments, nuclear and cytosol fractions were prepared from prostate, seminal vesicles, coagulation glands, preputial glands, spleen, submaxillary glands, kidneys, and pancreas from castrated male rats give (1,2,6,7 minus -3H)testosterone, and these fractions were then characterized by thin-layer and radio-gas chromatography with respect to their patterns of labeled steroids. Only prostate and seminal vesicles were found to contain significant amounts of nuclear 5alpha-(-3H)dihydrotestosterone. The major nuclear androgen was (-3H)testosterone that was the only detectable labeled steroid in coagulation glands, preputial glands, and spleen and that constituted 70% or more of the nuclear radioactivity in seminal vesicles, submaxillary glands, kidneys, and pancreas. These results indicate that testosterone itself may be the predominant active androgen principle in vivo in most androgen target organs and that conversion to 5alpha-dihydrotestosterone is generally not a prerequisite for androgen activity. Using an ultrasensitive micromodification of isoelectric focusing (cf. M. Katsumata and A. S. Goldman (1974), Biochem. Biophys. Acta 359, 112. It was possible to show that cytosol from kidney; submaxillary gland, thigh muscle, and levator ani muscle and nuclei from kidney and submaxillary gland contained androgen-binding proteins with pI's in the region 4.6-5.1 (\"4.6 minus 5.1 Complex\"). This complex also formed in vitro after incubation of (1,2,6,7 minus -3H)testosterone with cytosol from kidney and submaxillary gland. (1,2,6,7 minus -3H)Testosterone was bound with high affinity to receptor proteins in cytosol from both kidney, submaxillary gland, and thigh muscle with dissociation constants of 5.0 x 10 minus -12 M (kidney), 3.3 x 10 mi;nus -11 M and 4.1 x 10 minus -10 M (two types of binding sites, submaxillary gland), 2.4 x 10 minus -12 M (thigh muscle) and 1.9 x 10 minus -12 M (levator ani muscle). The number of binding sites was in all cases between 1 and 20 fmol/mg of protein. On the basis of these results the hypothesis is presented that a common class of testosterone receptors is present in most organs and that these receptors can be detected both in vivo and in vitro provided methods sensitive enough are utilized.", "contents": "Demonstration and partial characterization of cytosol receptors for testosterone. Androgen uptake was investigated in several peripheral organs after administration of (1,2,6,7 minus -3H)testosterone to castrated male rats. The animals were killed after 30 min, the organs were taken out, and the radioactivity was determined after tissue combustion. A relatively high accumulation of androgen was found in pancreas, adrenals, spleen, thigh muscle, kidneys, and liver in addition to the classical androgen target organs coagulation glands, seminal vesicles, prostate, preputial glands, and harderian glands. In a second serier of experiments, nuclear and cytosol fractions were prepared from prostate, seminal vesicles, coagulation glands, preputial glands, spleen, submaxillary glands, kidneys, and pancreas from castrated male rats give (1,2,6,7 minus -3H)testosterone, and these fractions were then characterized by thin-layer and radio-gas chromatography with respect to their patterns of labeled steroids. Only prostate and seminal vesicles were found to contain significant amounts of nuclear 5alpha-(-3H)dihydrotestosterone. The major nuclear androgen was (-3H)testosterone that was the only detectable labeled steroid in coagulation glands, preputial glands, and spleen and that constituted 70% or more of the nuclear radioactivity in seminal vesicles, submaxillary glands, kidneys, and pancreas. These results indicate that testosterone itself may be the predominant active androgen principle in vivo in most androgen target organs and that conversion to 5alpha-dihydrotestosterone is generally not a prerequisite for androgen activity. Using an ultrasensitive micromodification of isoelectric focusing (cf. M. Katsumata and A. S. Goldman (1974), Biochem. Biophys. Acta 359, 112. It was possible to show that cytosol from kidney; submaxillary gland, thigh muscle, and levator ani muscle and nuclei from kidney and submaxillary gland contained androgen-binding proteins with pI's in the region 4.6-5.1 (\"4.6 minus 5.1 Complex\"). This complex also formed in vitro after incubation of (1,2,6,7 minus -3H)testosterone with cytosol from kidney and submaxillary gland. (1,2,6,7 minus -3H)Testosterone was bound with high affinity to receptor proteins in cytosol from both kidney, submaxillary gland, and thigh muscle with dissociation constants of 5.0 x 10 minus -12 M (kidney), 3.3 x 10 mi;nus -11 M and 4.1 x 10 minus -10 M (two types of binding sites, submaxillary gland), 2.4 x 10 minus -12 M (thigh muscle) and 1.9 x 10 minus -12 M (levator ani muscle). The number of binding sites was in all cases between 1 and 20 fmol/mg of protein. On the basis of these results the hypothesis is presented that a common class of testosterone receptors is present in most organs and that these receptors can be detected both in vivo and in vitro provided methods sensitive enough are utilized."} {"id": "PMID:167817", "title": "Fucosyl-glycoprotein and precursor polls in HeLa cells.", "content": "An enzymatic-radioactive isotope method has been developed for the direct quantitation of L-fucose in amounts as low at 0.5 plus or minus 0.05 nmol. Fucose kinase is used to transfer [32-P]phosphate from ATP to [3-H]fucose. The labeled enzymatic products are then separated electrophoretically and the amount and specific activity of the fucose are determined from the known specific activity of the phosphate donor. This assay has been used to measure the GDP-L-fucose and macromolecualar fucose in HeLa cells after extraction and purification of the sugar. It has been determined there are 0.5 nmol of GDP-L-fucose in 10-7 cells with a nine- to tenfold dilution of specific activity in converting L-[3-H] fucose to GDP-L-[3-H]fucose. After 2 to 3 days of labeling, the GDP-L-[3-H]fucose pool is essentially at equilibrium with the macromolecular pool, and hence it can be concluded that the dilution of label is due to a nine- to tenfold contribution to GDP-L-fucose from an endogenous source, as compared to exogenously supplied fucose. The fucosyl-glycoprotein pool has been shown to be much larger containing 6 to 8 nmol of fucose in 10-7 cells. It has further been shown that GDP-fucose is the only soluble fucose intermediate present in significant amount.", "contents": "Fucosyl-glycoprotein and precursor polls in HeLa cells. An enzymatic-radioactive isotope method has been developed for the direct quantitation of L-fucose in amounts as low at 0.5 plus or minus 0.05 nmol. Fucose kinase is used to transfer [32-P]phosphate from ATP to [3-H]fucose. The labeled enzymatic products are then separated electrophoretically and the amount and specific activity of the fucose are determined from the known specific activity of the phosphate donor. This assay has been used to measure the GDP-L-fucose and macromolecualar fucose in HeLa cells after extraction and purification of the sugar. It has been determined there are 0.5 nmol of GDP-L-fucose in 10-7 cells with a nine- to tenfold dilution of specific activity in converting L-[3-H] fucose to GDP-L-[3-H]fucose. After 2 to 3 days of labeling, the GDP-L-[3-H]fucose pool is essentially at equilibrium with the macromolecular pool, and hence it can be concluded that the dilution of label is due to a nine- to tenfold contribution to GDP-L-fucose from an endogenous source, as compared to exogenously supplied fucose. The fucosyl-glycoprotein pool has been shown to be much larger containing 6 to 8 nmol of fucose in 10-7 cells. It has further been shown that GDP-fucose is the only soluble fucose intermediate present in significant amount."} {"id": "PMID:167818", "title": "Molecular weights of estrogen and androgen binding proteins in the liver of Xenopus laevis.", "content": "[3-H]Estradiol-17beta and [3-H]dihydrotestosterone binding proteins in the cytosol fraction of liver from both male and female Xenopus laevis were characterized by electrophoresis on polyacrylamide gels. These binding proteins, which were indistinguishable based upon their mobilities on gels of different acrylamide concentrations, migrated as single components with a molecular weight of 2.0 x 10-4. Separation of native or sodium dodecyl sulfate denatured specific estrogen-binding components on dodecyl sulfate free acrylamide gels gave similar results, i.e., a single species of molecular weight 2.0-2.5 x 10-4. The same molecular weight also was obtained when cytosol was prepared in the presence of either diisopropyl fluorophosphate or phenylmethanesulfonyl fluoride, protease inhibitors. Evidence that the liver components binding either [3-H]estradiol-17-beta or [3-H]dihydrotestosterone were not plasma contaminants was provided by the observation that the plasma sex-steroid binding globulin of Xenopus had a different mobility when separated by polyacrylamide gel electrophoresis.", "contents": "Molecular weights of estrogen and androgen binding proteins in the liver of Xenopus laevis. [3-H]Estradiol-17beta and [3-H]dihydrotestosterone binding proteins in the cytosol fraction of liver from both male and female Xenopus laevis were characterized by electrophoresis on polyacrylamide gels. These binding proteins, which were indistinguishable based upon their mobilities on gels of different acrylamide concentrations, migrated as single components with a molecular weight of 2.0 x 10-4. Separation of native or sodium dodecyl sulfate denatured specific estrogen-binding components on dodecyl sulfate free acrylamide gels gave similar results, i.e., a single species of molecular weight 2.0-2.5 x 10-4. The same molecular weight also was obtained when cytosol was prepared in the presence of either diisopropyl fluorophosphate or phenylmethanesulfonyl fluoride, protease inhibitors. Evidence that the liver components binding either [3-H]estradiol-17-beta or [3-H]dihydrotestosterone were not plasma contaminants was provided by the observation that the plasma sex-steroid binding globulin of Xenopus had a different mobility when separated by polyacrylamide gel electrophoresis."} {"id": "PMID:167819", "title": "Magnetic resonance and kinetic studies of pyruvate, phosphate dikinase. Interaction of oxalate with the phosphorylated form of the enzyme.", "content": "Pyruvate, orthophosphate dikinase (EC 2.7.9.1) carries out its catalytic function in three successive partial reactions, the final step being the reaction of pyruvate with a stable phosphoenzyme intermediate to give phosphoenolpyruvate and free enzyme (Evans, H.J., and Wood, H. G. (1968), Proc. Natl. Acad. Sci. U.S.A. 61, 1448). Interactions of oxalate, a structural analog of enolpyruvate, with the phosphorylated form of the enzyme have been investigated by kinetic inhibition measurements and by magnetic resonance studies of manganous ion complexes with the enzyme. Oxalate inhibits the reaction catalyzed by pyruvate, phosphate dikinase, and the inhibition is linearly competitive with respect to pyruvate. The inhibitor constant for oxalate of 25 mu-M is fourfold lower than the Michaelis constant for pyruvate. The enhancement in the longitudinal relaxation rate of water protons (PRR) which occurs upon binding of Mn(II) to the enzyme has been used to monitor binding of oxalate to Mn(II)-enzyme complexes. PRR titrations indicate that the dissociation constant of oxalate from the Mn(II) complex of the free form of the enzyme is an order of magnitude weaker than the kinetically determined Ki. On the other hand, titrations of solutions which contain the phosphorylated form of the enzyme reveal a much stronger binding of oxalate. Moreover, the strength of oxalate binding to the phosphorylated enzyme is a function both of the species and of the concentration of monovalent cations in the solution. In the presence of Tl+, which has the most favorable activator constant for the final partial reaction, the dissociation constant for oxalate from its complex with the phosphorylated enzyme is less than 1 mu-M. Electron paramagnetic resonance (EPR) spectra for the enzyme-bound Mn(II) are sensitive to structural perturbations which occur upon binding of substrates or of oxalate to the enzyme. The EPR spectrum for the Mn(II)-phosphoenzyme-oxalate species is distinguished from spectra for other complexes of the enzyme by unusually narrow line widths and consequent resolution of fine structure from electronic quadrupole splitting. The narrow lines in the EPR spectrum are indicative of a rigid, pseudocrystalline environment for the bound Mn(II). The magnitude and frequency dependence of the PRR for the Mn(II)-phosphoenzyme-oxalate complex indicate that if any water molecules are bound to the Mn(II), their exchange with the bulk water is severely retarded. The kinetic and magnetic resonance studies support the hypothesis that oxalate mimics the reactive intermediate, enolpyruvate, in a complex with the phosphorylated enzyme which may resemble the structure of the transition state of the final partial reaction.", "contents": "Magnetic resonance and kinetic studies of pyruvate, phosphate dikinase. Interaction of oxalate with the phosphorylated form of the enzyme. Pyruvate, orthophosphate dikinase (EC 2.7.9.1) carries out its catalytic function in three successive partial reactions, the final step being the reaction of pyruvate with a stable phosphoenzyme intermediate to give phosphoenolpyruvate and free enzyme (Evans, H.J., and Wood, H. G. (1968), Proc. Natl. Acad. Sci. U.S.A. 61, 1448). Interactions of oxalate, a structural analog of enolpyruvate, with the phosphorylated form of the enzyme have been investigated by kinetic inhibition measurements and by magnetic resonance studies of manganous ion complexes with the enzyme. Oxalate inhibits the reaction catalyzed by pyruvate, phosphate dikinase, and the inhibition is linearly competitive with respect to pyruvate. The inhibitor constant for oxalate of 25 mu-M is fourfold lower than the Michaelis constant for pyruvate. The enhancement in the longitudinal relaxation rate of water protons (PRR) which occurs upon binding of Mn(II) to the enzyme has been used to monitor binding of oxalate to Mn(II)-enzyme complexes. PRR titrations indicate that the dissociation constant of oxalate from the Mn(II) complex of the free form of the enzyme is an order of magnitude weaker than the kinetically determined Ki. On the other hand, titrations of solutions which contain the phosphorylated form of the enzyme reveal a much stronger binding of oxalate. Moreover, the strength of oxalate binding to the phosphorylated enzyme is a function both of the species and of the concentration of monovalent cations in the solution. In the presence of Tl+, which has the most favorable activator constant for the final partial reaction, the dissociation constant for oxalate from its complex with the phosphorylated enzyme is less than 1 mu-M. Electron paramagnetic resonance (EPR) spectra for the enzyme-bound Mn(II) are sensitive to structural perturbations which occur upon binding of substrates or of oxalate to the enzyme. The EPR spectrum for the Mn(II)-phosphoenzyme-oxalate species is distinguished from spectra for other complexes of the enzyme by unusually narrow line widths and consequent resolution of fine structure from electronic quadrupole splitting. The narrow lines in the EPR spectrum are indicative of a rigid, pseudocrystalline environment for the bound Mn(II). The magnitude and frequency dependence of the PRR for the Mn(II)-phosphoenzyme-oxalate complex indicate that if any water molecules are bound to the Mn(II), their exchange with the bulk water is severely retarded. The kinetic and magnetic resonance studies support the hypothesis that oxalate mimics the reactive intermediate, enolpyruvate, in a complex with the phosphorylated enzyme which may resemble the structure of the transition state of the final partial reaction."} {"id": "PMID:167820", "title": "A study of protein-sodium dodecyl sulfate complexes by transient electric birefringence.", "content": "The method of transient electric birefringence has been applied to study the conformation of protein-sodium dodecyl sulfate complexes. A model of a deformable prolate ellipsoid has been proposed for the protein-dodecyl sulfate complex. This model is compared to the models proposed by J. A. Reynolds and C. Tanford (1970), J. Biol. Chem. 245, 5161) and K. Shirahama, K. Tsujii, and T. Takagi (1974, J. Biochem. 75, 309). Differences between these latter two models are resolved by the model presented here. In addition, it has been demonstrated that protein molecular weights may be obtained from the slow relaxation time for transient electric birefringence of protein-dodecyl sulfate complexes.", "contents": "A study of protein-sodium dodecyl sulfate complexes by transient electric birefringence. The method of transient electric birefringence has been applied to study the conformation of protein-sodium dodecyl sulfate complexes. A model of a deformable prolate ellipsoid has been proposed for the protein-dodecyl sulfate complex. This model is compared to the models proposed by J. A. Reynolds and C. Tanford (1970), J. Biol. Chem. 245, 5161) and K. Shirahama, K. Tsujii, and T. Takagi (1974, J. Biochem. 75, 309). Differences between these latter two models are resolved by the model presented here. In addition, it has been demonstrated that protein molecular weights may be obtained from the slow relaxation time for transient electric birefringence of protein-dodecyl sulfate complexes."} {"id": "PMID:167821", "title": "Characterization of procollagen-derived peptides unique to the precursor molecule.", "content": "A disulfide-bonded fragment with a molecular weight of about 100,000 was identified in the medium of cultured chick cranial bone and its derivation from procollagen was established by immunological criteria. The molecular weight of the fragment was reduced to 33,000 after cleavage of disulfide bonds, indicating a triple-stranded structure. The amino acid composition of the fragment lacked hydroxyproline and hydroxylysine and differed markedly from that of collagen in other respects. A similar but somewhat larger fragment was isolated after bacterial collagenase digestion of chick bone procollagen purified by chromatography on DEAE-cellulose. The characterization and comparison of these fragments further define the nature of the additional regions in procollagen and, when combined with information derived from studies of acid-extracted and dermatosparactic procollagens, support a mechanism for the conversion of procollagen to collagen which involves more than one proteolytic step.", "contents": "Characterization of procollagen-derived peptides unique to the precursor molecule. A disulfide-bonded fragment with a molecular weight of about 100,000 was identified in the medium of cultured chick cranial bone and its derivation from procollagen was established by immunological criteria. The molecular weight of the fragment was reduced to 33,000 after cleavage of disulfide bonds, indicating a triple-stranded structure. The amino acid composition of the fragment lacked hydroxyproline and hydroxylysine and differed markedly from that of collagen in other respects. A similar but somewhat larger fragment was isolated after bacterial collagenase digestion of chick bone procollagen purified by chromatography on DEAE-cellulose. The characterization and comparison of these fragments further define the nature of the additional regions in procollagen and, when combined with information derived from studies of acid-extracted and dermatosparactic procollagens, support a mechanism for the conversion of procollagen to collagen which involves more than one proteolytic step."} {"id": "PMID:167822", "title": "Conformational changes in the progesterone binding globulin-progesterone complex.", "content": "An improved purification procedure for the progesterone-binding globulin (PBG) of the pregnant guinea pig has been developed utilizing sulfopropyl Sephadex, a strong cation exchanger, in the first step. The method exploits the low pI (2.8) and favorable acid stability of the glycoprotein. Subsequent chromatographies on DEAE-cellulose and Sephadex G-200 afford a highly purified PBG that exhibits the previously observed polydispersity (R.M. Burton et al. (1974), Biochemistry 13, 3554-3561). Circular dichroism, optical rotatory dispersion, and difference uv spectra all indicate the purified protein to undergo a conformational transition upon forming a complex with a steroid ligand. The CD and ORD spectra cannot be interpreted in terms of tertiary structure probably due to carbohydrate contributions. However, the difference spectra indicate strong perturbation of both a tryptophan residue and the steroid chromophore in the complex.", "contents": "Conformational changes in the progesterone binding globulin-progesterone complex. An improved purification procedure for the progesterone-binding globulin (PBG) of the pregnant guinea pig has been developed utilizing sulfopropyl Sephadex, a strong cation exchanger, in the first step. The method exploits the low pI (2.8) and favorable acid stability of the glycoprotein. Subsequent chromatographies on DEAE-cellulose and Sephadex G-200 afford a highly purified PBG that exhibits the previously observed polydispersity (R.M. Burton et al. (1974), Biochemistry 13, 3554-3561). Circular dichroism, optical rotatory dispersion, and difference uv spectra all indicate the purified protein to undergo a conformational transition upon forming a complex with a steroid ligand. The CD and ORD spectra cannot be interpreted in terms of tertiary structure probably due to carbohydrate contributions. However, the difference spectra indicate strong perturbation of both a tryptophan residue and the steroid chromophore in the complex."} {"id": "PMID:167823", "title": "Actions of insulin, epinephrine, and dibutyryl cyclic adenosine 5'-monophosphate on fat cell protein phosphorylations. Cyclic adenosine 5'-monophosphate dependent and independent mechanisms.", "content": "Endogenous and hormone-induced protein (polypeptide) phosphorylations were studied in isolated rat fat cells, in fat pads, and in subcellular fractions obtained from fat tissue under different physiological conditions. Insulin (25-100 muU/ml) increased the incorporation of 32P into two proteins: insulin-phosphorylated proteins (IPP 140 and IPP 50; similar to 140,000 and 50,000 daltons, respectively). Epinephrine (10(-7)-10(-6) M) increased the incorporation of 32P into another protein: epinephrine-phosphorylated protein (EPP 60-65; similar to 60,000-65,000 daltons). Endogenous IPP 140 phosphorylation in fat cells obtained from fasted and refed rats was similar to that of insulin in normal cells. Studies of insulin and epinephrine interactions showed that insulin increased IPP 140 phosphorylation even in the presence of epinephrine or lithium (25 mM times 10(-3) M). dibutyryl cyclic AMP (5 times 10(-4) M) markedly stimulated EPP 60-65 phosphorylation, but neither epinephrine (10(-7)-10(-6) M) nor dibutyryl cyclic AMP reproduced insulin's phosphorylation of APP 140. Lithium inhibited both endogenous and epinephrine-stimulate EPP 60-65 phosphorylation, but did not inhibit that induced by dibutyryl cyclic AMP. These findings suggest that insulin stimulated a specific, cyclic AMP independent protein kinase for IPP 140 phosphorylation. Cell-free extracts from insulin-treated fat tissue catalyzed the specific transfer of 32P from ATP to IPP 140 more rapidly than control extracts. No differences in the total receptor protein or total protein kinase activity using [gamma(-32P]ATP were noted between insulin-treated and control preparations. IPP 140 may be either (a) an insulin-sensitive protein kinase (phosphotransferase) or (b) a protein whose function is regulated by an insulin-sensitive protein kinase or phosphatase.", "contents": "Actions of insulin, epinephrine, and dibutyryl cyclic adenosine 5'-monophosphate on fat cell protein phosphorylations. Cyclic adenosine 5'-monophosphate dependent and independent mechanisms. Endogenous and hormone-induced protein (polypeptide) phosphorylations were studied in isolated rat fat cells, in fat pads, and in subcellular fractions obtained from fat tissue under different physiological conditions. Insulin (25-100 muU/ml) increased the incorporation of 32P into two proteins: insulin-phosphorylated proteins (IPP 140 and IPP 50; similar to 140,000 and 50,000 daltons, respectively). Epinephrine (10(-7)-10(-6) M) increased the incorporation of 32P into another protein: epinephrine-phosphorylated protein (EPP 60-65; similar to 60,000-65,000 daltons). Endogenous IPP 140 phosphorylation in fat cells obtained from fasted and refed rats was similar to that of insulin in normal cells. Studies of insulin and epinephrine interactions showed that insulin increased IPP 140 phosphorylation even in the presence of epinephrine or lithium (25 mM times 10(-3) M). dibutyryl cyclic AMP (5 times 10(-4) M) markedly stimulated EPP 60-65 phosphorylation, but neither epinephrine (10(-7)-10(-6) M) nor dibutyryl cyclic AMP reproduced insulin's phosphorylation of APP 140. Lithium inhibited both endogenous and epinephrine-stimulate EPP 60-65 phosphorylation, but did not inhibit that induced by dibutyryl cyclic AMP. These findings suggest that insulin stimulated a specific, cyclic AMP independent protein kinase for IPP 140 phosphorylation. Cell-free extracts from insulin-treated fat tissue catalyzed the specific transfer of 32P from ATP to IPP 140 more rapidly than control extracts. No differences in the total receptor protein or total protein kinase activity using [gamma(-32P]ATP were noted between insulin-treated and control preparations. IPP 140 may be either (a) an insulin-sensitive protein kinase (phosphotransferase) or (b) a protein whose function is regulated by an insulin-sensitive protein kinase or phosphatase."} {"id": "PMID:167824", "title": "2-substituted derivatives of adenosine and inosine cyclic 3',5'-phosphate. Synthesis, enzymic activity, and analysis of the structural requirements of the binding locale of the 2-substituent on bovine brain protein kinase.", "content": "A number of 2-substituted cyclic nucleotide derivatives were synthesized and investigated as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterase. Ring closure of 5-amino-1-beta-D-ribofuranosylimidazol-4-carboxamide cyclic 3',5'-phosphate (1) with various aldehydes according to a new procedure (Meyer, R. B., Jr., Shuman, D.A., and Robins, R. K. (1974), J. Am. Chem. Soc. 96, 4962) gave new derivatives of adenosine cyclic 3',5'-phosphate with the following 2-substituents: n-propyl, n-hexl, n-octyl, n-decyl, styryl, o-methoxyphenyl, and 2-thienyl. Alkylation of 2-mercaptoadenosine cyclic 3',5'-phosphate (20, Meyer et al., 1974) gave new cAMP derivatives with the following 2-substituent: ethylthio, n-propylthio, isopropylthio, allylthio, n-decylthio, and benzylthio. Deamination of 2-methyl-,2-n-butyl-, and 2-ethylthioadenosine cyclic 3',5'-phosphate. Using multiple regression analysis, a striking relationship was found between the relative potency of the compounds as activators of bovine brain cAMP-dependent protein kinase and parameters describing the hydrophobic, steric, and electronic character of the substituents on these compounds. All compounds were substrates for a cyclic nucleotide phosphodiesterase preparation from rabbit kidney. Additionally, the compounds were as a group, good inhibitors of the hydrolysis of cAMP by phosphodiesterase preparations from rabbit lung, beef heart, and dog heart.", "contents": "2-substituted derivatives of adenosine and inosine cyclic 3',5'-phosphate. Synthesis, enzymic activity, and analysis of the structural requirements of the binding locale of the 2-substituent on bovine brain protein kinase. A number of 2-substituted cyclic nucleotide derivatives were synthesized and investigated as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterase. Ring closure of 5-amino-1-beta-D-ribofuranosylimidazol-4-carboxamide cyclic 3',5'-phosphate (1) with various aldehydes according to a new procedure (Meyer, R. B., Jr., Shuman, D.A., and Robins, R. K. (1974), J. Am. Chem. Soc. 96, 4962) gave new derivatives of adenosine cyclic 3',5'-phosphate with the following 2-substituents: n-propyl, n-hexl, n-octyl, n-decyl, styryl, o-methoxyphenyl, and 2-thienyl. Alkylation of 2-mercaptoadenosine cyclic 3',5'-phosphate (20, Meyer et al., 1974) gave new cAMP derivatives with the following 2-substituent: ethylthio, n-propylthio, isopropylthio, allylthio, n-decylthio, and benzylthio. Deamination of 2-methyl-,2-n-butyl-, and 2-ethylthioadenosine cyclic 3',5'-phosphate. Using multiple regression analysis, a striking relationship was found between the relative potency of the compounds as activators of bovine brain cAMP-dependent protein kinase and parameters describing the hydrophobic, steric, and electronic character of the substituents on these compounds. All compounds were substrates for a cyclic nucleotide phosphodiesterase preparation from rabbit kidney. Additionally, the compounds were as a group, good inhibitors of the hydrolysis of cAMP by phosphodiesterase preparations from rabbit lung, beef heart, and dog heart."} {"id": "PMID:167825", "title": "Temperature dependence of the optical activity of human serum low density lipoprotein. The role of lipids.", "content": "Low density lipoprotein (LDL) (1.024-1.045 G/cm3) was prepared by ultracentrifugal flotation from serum of normal fasting subjects. Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra in the ultraviolet region were measured at 2, 25, and 37 degrees on LDL, lipid extracted from LDL, and on pure component lipids. All exhibit reversible, temperature-dependent optical activities. Sphingomyelin has a strong negative CD band around 195 nm. Cholesterol and cholesteryl esters have a CD minimum at 208 nm. They have positive CD bands around 201 and 198 nm which decrease sharply and become negative at 198 and 193 nm, respectively. The CD of the total lipid extract of LDL is negative and drops monotonically below 200 nm. Thus, the lipid moiety could account for the increasing negativity of the CD of LDL below 195 nm. After subtraction of the ellipticity corresponding to amounts of lipids in organic solvents equivalent to those found in LDL, the 208-210 nm trough of LDL diminishes markedly. This is accompanied by a blue-shift of the extrema from 195-196 to 193 nm and an increase in the magnitude of the positive ellipticity. The fractions of helix and of beta form in the protein, determined by the method of Y. H. Chen, J. T. Yang, and K. H. Chau ((1974), Biochemistry 13, 3350), in the wavelength interval of 250-240 nm, remain essentially unchanged between 2 and 37 degrees. These observations suggest that a substantial part of the thermal change in the CD spectrum of LDL between 208 and 210 nm may be attributable to lipids.", "contents": "Temperature dependence of the optical activity of human serum low density lipoprotein. The role of lipids. Low density lipoprotein (LDL) (1.024-1.045 G/cm3) was prepared by ultracentrifugal flotation from serum of normal fasting subjects. Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra in the ultraviolet region were measured at 2, 25, and 37 degrees on LDL, lipid extracted from LDL, and on pure component lipids. All exhibit reversible, temperature-dependent optical activities. Sphingomyelin has a strong negative CD band around 195 nm. Cholesterol and cholesteryl esters have a CD minimum at 208 nm. They have positive CD bands around 201 and 198 nm which decrease sharply and become negative at 198 and 193 nm, respectively. The CD of the total lipid extract of LDL is negative and drops monotonically below 200 nm. Thus, the lipid moiety could account for the increasing negativity of the CD of LDL below 195 nm. After subtraction of the ellipticity corresponding to amounts of lipids in organic solvents equivalent to those found in LDL, the 208-210 nm trough of LDL diminishes markedly. This is accompanied by a blue-shift of the extrema from 195-196 to 193 nm and an increase in the magnitude of the positive ellipticity. The fractions of helix and of beta form in the protein, determined by the method of Y. H. Chen, J. T. Yang, and K. H. Chau ((1974), Biochemistry 13, 3350), in the wavelength interval of 250-240 nm, remain essentially unchanged between 2 and 37 degrees. These observations suggest that a substantial part of the thermal change in the CD spectrum of LDL between 208 and 210 nm may be attributable to lipids."} {"id": "PMID:167826", "title": "The DNA melting transition in aqueous magnesium salt solutions.", "content": "The melting transition of the magnesium salt of DNA has been systematically examined in the presence of various types of anions. The addition of ClO4- to a concentration of 3.0 N results in the biphasic optical transition, with the first phase exhibiting rapid reversibility and independence of the DNA concentration. This subtransition, which is interpreted as an intramolecular condensation to a collapsed form of DNA, is followed by a DNA concentration-dependent aggregation reaction. The aggregation can be reversed by increasing the ClO4- concentration to 6.0 N while elevating the temperature to post-transition levels. Alternatively, both the collapse and the aggregation can be prevented by melting in the presence of trichloroacetate, the most strongly chaotropic solvent for DNA which has been reported (K. Hamaguchi and E. P. Geiduschek (1962), J. Am. Chem. Soc. 84, 1329). The forces responsible for mediating both the collapse and the aggregation are superficially similar to those involved in maintaining duplex stability. The collapsed form, in particular, possibly possesses features in common with the condensed structures which can be produced in aqueous solution of certain polymers, such as polyethylene glycol (Lerman, L.S. (1971), Proc. Natl. Acad. Sci. U.S.A. 68, 1886).", "contents": "The DNA melting transition in aqueous magnesium salt solutions. The melting transition of the magnesium salt of DNA has been systematically examined in the presence of various types of anions. The addition of ClO4- to a concentration of 3.0 N results in the biphasic optical transition, with the first phase exhibiting rapid reversibility and independence of the DNA concentration. This subtransition, which is interpreted as an intramolecular condensation to a collapsed form of DNA, is followed by a DNA concentration-dependent aggregation reaction. The aggregation can be reversed by increasing the ClO4- concentration to 6.0 N while elevating the temperature to post-transition levels. Alternatively, both the collapse and the aggregation can be prevented by melting in the presence of trichloroacetate, the most strongly chaotropic solvent for DNA which has been reported (K. Hamaguchi and E. P. Geiduschek (1962), J. Am. Chem. Soc. 84, 1329). The forces responsible for mediating both the collapse and the aggregation are superficially similar to those involved in maintaining duplex stability. The collapsed form, in particular, possibly possesses features in common with the condensed structures which can be produced in aqueous solution of certain polymers, such as polyethylene glycol (Lerman, L.S. (1971), Proc. Natl. Acad. Sci. U.S.A. 68, 1886)."} {"id": "PMID:167827", "title": "Malate dehydrogenase, anticooperative NADH, and L-malate binding in ternary complexes with Supernatant pig heart enzyme.", "content": "Supernatant malate dehydrogenase from pig heart, a dimeric protein containing two very similar or identical subunits, shows negatively cooperative (anticooperative) interactions between NADH binding sites in the presence, but not in the absence, of 0.1 M L-malate. This behavior is observed consitently whether the technique used employs protein fluorescence quenching, NADH fluorescence enhancement, or ultrafiltration dialysis. Fluorescence titration shows that L-malate is also anticooperatively bound in the presence of saturating concentrations of NADH. The data are consistent with an \"induced asymmetry\" model in which conformational change accompanies the formation of the ternary complex. Two of the three chromatographically resolvable forms of the enzyme have been tested and found to have anticooperative behavior.", "contents": "Malate dehydrogenase, anticooperative NADH, and L-malate binding in ternary complexes with Supernatant pig heart enzyme. Supernatant malate dehydrogenase from pig heart, a dimeric protein containing two very similar or identical subunits, shows negatively cooperative (anticooperative) interactions between NADH binding sites in the presence, but not in the absence, of 0.1 M L-malate. This behavior is observed consitently whether the technique used employs protein fluorescence quenching, NADH fluorescence enhancement, or ultrafiltration dialysis. Fluorescence titration shows that L-malate is also anticooperatively bound in the presence of saturating concentrations of NADH. The data are consistent with an \"induced asymmetry\" model in which conformational change accompanies the formation of the ternary complex. Two of the three chromatographically resolvable forms of the enzyme have been tested and found to have anticooperative behavior."} {"id": "PMID:167828", "title": "The role of arginyl residues in directing carboxymethylation of horse liver alcohol dehydrogenase.", "content": "The selective carboxymethylation by iodoacetate of Cys-46 in the active center of horse liver alcohol dehydrogenase has been shown to be mediated by interaction of the anionic reagent with the arginyl residue(s) previously shown to be responsible for binding NADH (L.G. Lange, J.F. Riordan, and B.L. Vallee (1974), Biochemistry 13, 4361). Thus, sequential and reversible chemical modification of arginine with butanedione and of cysteine with pmercuribenzoate demonstrate that the essential thiol groups are not affected by arginine modification. Importantly, the rate of incorporation of [14C]idoacetate into native horse liver alcohol dehydrogenase is ten times faster than that for the butanedione-modified enzyme. Moreover, as evidenced by peptide isolation, the radiolabel incorporated into the latter occurs at low levels in several different peptides as opposed to the single, strongly labeled CmCys-46 peptide obtained from the native enzyme. The demonstration that the arginyl residue(s) involved in coenzyme binding promotes enhanced reactivity of the active site thiol supports the general hypothesis that the spatial arrangement of structural features allowing expression of enzymatic function may also account for enhanced chemical reactivity of certain active site residues (B.L Vallee and J.F. Riordan (1969), Annu. Rev. Biochem. 38, 733).", "contents": "The role of arginyl residues in directing carboxymethylation of horse liver alcohol dehydrogenase. The selective carboxymethylation by iodoacetate of Cys-46 in the active center of horse liver alcohol dehydrogenase has been shown to be mediated by interaction of the anionic reagent with the arginyl residue(s) previously shown to be responsible for binding NADH (L.G. Lange, J.F. Riordan, and B.L. Vallee (1974), Biochemistry 13, 4361). Thus, sequential and reversible chemical modification of arginine with butanedione and of cysteine with pmercuribenzoate demonstrate that the essential thiol groups are not affected by arginine modification. Importantly, the rate of incorporation of [14C]idoacetate into native horse liver alcohol dehydrogenase is ten times faster than that for the butanedione-modified enzyme. Moreover, as evidenced by peptide isolation, the radiolabel incorporated into the latter occurs at low levels in several different peptides as opposed to the single, strongly labeled CmCys-46 peptide obtained from the native enzyme. The demonstration that the arginyl residue(s) involved in coenzyme binding promotes enhanced reactivity of the active site thiol supports the general hypothesis that the spatial arrangement of structural features allowing expression of enzymatic function may also account for enhanced chemical reactivity of certain active site residues (B.L Vallee and J.F. Riordan (1969), Annu. Rev. Biochem. 38, 733)."} {"id": "PMID:167829", "title": "Nucleotide regulation of a eukaryotic protein synthesis initiation complex;.", "content": "Formation of a ternary initiation complex containing Met-tRNAf, GTP and eukaryotic initiation factor 2, is the first step in sequential assembly of the initiation complex. The concentration of GTP required for half maximal formation of the ternary complex is 2.5 with 10(-6) M. GDP is a potent competitive inhibitor of ternary complex formation with Ki = 3.4 with 10(-7) M. The nucleotide binding site on eukaryotic initiation factor 2 demonstrates relative specificity for GDP with KD(GDP) = 3.0 with 10(-8) M; 100-fold higher concentrations of GTP than GDP are required for displacement of either [(3)H]GDP or [(3)h]gtp from the necleotide binding site. An ATP-dependent stimulation of ternary complex formation observed in partially purified initiation factor preparations is due to nucleoside diphosphate kinase (EC 2.7.4.6) which serves to remove inhibitory levels of GDP by phosphorylation with ATP. Since GTP is hydrolyzed to GDP during protein synthesis, this provides a mechanism by which the ATP:ADP ratio may regulate the rate of initiation of protein synthesis.", "contents": "Nucleotide regulation of a eukaryotic protein synthesis initiation complex;. Formation of a ternary initiation complex containing Met-tRNAf, GTP and eukaryotic initiation factor 2, is the first step in sequential assembly of the initiation complex. The concentration of GTP required for half maximal formation of the ternary complex is 2.5 with 10(-6) M. GDP is a potent competitive inhibitor of ternary complex formation with Ki = 3.4 with 10(-7) M. The nucleotide binding site on eukaryotic initiation factor 2 demonstrates relative specificity for GDP with KD(GDP) = 3.0 with 10(-8) M; 100-fold higher concentrations of GTP than GDP are required for displacement of either [(3)H]GDP or [(3)h]gtp from the necleotide binding site. An ATP-dependent stimulation of ternary complex formation observed in partially purified initiation factor preparations is due to nucleoside diphosphate kinase (EC 2.7.4.6) which serves to remove inhibitory levels of GDP by phosphorylation with ATP. Since GTP is hydrolyzed to GDP during protein synthesis, this provides a mechanism by which the ATP:ADP ratio may regulate the rate of initiation of protein synthesis."} {"id": "PMID:167830", "title": "Studies of coenzyme binding to rabbit muscle glyceraldehyde-3-phoshate dehydrogenase.", "content": "The binding of NAD+, NADH and adenosine diphosphoribose (Ado-PP-Rib) to a stable, highly active and nucleotide-free preparation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) has been studied. All three nucleotides quench the protein fluorescence to the same extent when they bind to the enzyme, and this property has been used to measure the dissociation constants for the two high-affinity binding sites for the nucleotides. The results indicate negative interactions between, or non-identify of, these two binding sites, to which NAD+ and NADH bind with similar affinity. The binding of NAD+ to the enzyme has been studied by spectrophotometric titrations at 360 nm. It appears that the binding of NAD+ to each of the four subunits of the enzyme contributes equally to the intensity of this 'Racker' band. The dissociation constants associated with the binding of the third and fourth molecules of NAD+ estimated from such titrations confirm some previous estimates. The binding of NADH to the enzyme causes a decrease of intensity of the absorbance of the coenzyme at 340 nm, and the dissociation constants for binding of the third and fourth molecules of NADH have been estimated from spectrophotometric titrations. They are the same as those for NAD+. Judging by the apparent dissociation constants, negative interactions on binding the third molecule of NAD+ or NADH are more marked than those associated with the binding of the second and fourth molecules, suggesting that a major conformational change occurs at half-saturation of the tetramer with coenzyme.", "contents": "Studies of coenzyme binding to rabbit muscle glyceraldehyde-3-phoshate dehydrogenase. The binding of NAD+, NADH and adenosine diphosphoribose (Ado-PP-Rib) to a stable, highly active and nucleotide-free preparation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) has been studied. All three nucleotides quench the protein fluorescence to the same extent when they bind to the enzyme, and this property has been used to measure the dissociation constants for the two high-affinity binding sites for the nucleotides. The results indicate negative interactions between, or non-identify of, these two binding sites, to which NAD+ and NADH bind with similar affinity. The binding of NAD+ to the enzyme has been studied by spectrophotometric titrations at 360 nm. It appears that the binding of NAD+ to each of the four subunits of the enzyme contributes equally to the intensity of this 'Racker' band. The dissociation constants associated with the binding of the third and fourth molecules of NAD+ estimated from such titrations confirm some previous estimates. The binding of NADH to the enzyme causes a decrease of intensity of the absorbance of the coenzyme at 340 nm, and the dissociation constants for binding of the third and fourth molecules of NADH have been estimated from spectrophotometric titrations. They are the same as those for NAD+. Judging by the apparent dissociation constants, negative interactions on binding the third molecule of NAD+ or NADH are more marked than those associated with the binding of the second and fourth molecules, suggesting that a major conformational change occurs at half-saturation of the tetramer with coenzyme."} {"id": "PMID:167831", "title": "EPR studies on compound I of horseradish peroxidase.", "content": "Compound I of horseradish peroxidase (donor: hydrogen-peroxide oxidoreductase EC 1.11.1.7) was studied by EPR at low temperatures. An asymmetric signal was found, about 15 Gauss wide and with a g-value of 1.995, which could be detected only at temperatures below 20 K and which had an intensity corresponding to about 1% of the heme content. In a titration with H2O2, the signal intensity was proportional to the concentration of Compound I, reaching a maximum when equivalent amounts of H2O2 were added. This indicates that the signal is not due to an impurity, and it is suggested that a free radical is formed, relaxed by a near-by fast-relaxing iron.", "contents": "EPR studies on compound I of horseradish peroxidase. Compound I of horseradish peroxidase (donor: hydrogen-peroxide oxidoreductase EC 1.11.1.7) was studied by EPR at low temperatures. An asymmetric signal was found, about 15 Gauss wide and with a g-value of 1.995, which could be detected only at temperatures below 20 K and which had an intensity corresponding to about 1% of the heme content. In a titration with H2O2, the signal intensity was proportional to the concentration of Compound I, reaching a maximum when equivalent amounts of H2O2 were added. This indicates that the signal is not due to an impurity, and it is suggested that a free radical is formed, relaxed by a near-by fast-relaxing iron."} {"id": "PMID:167832", "title": "Isolation of an activator of multiple forms of cyclic nucleotides phosphodiesterase of rat cerebrum by isoelectric focusing.", "content": "An isoelectric focusing technique was used to isolate multiple forms of cyclic nucleotide phosphodiesterase from a 105 000 times g soluble supernatant fraction of sonicated rat cerebrum. These separated peaks of activity had iso-electric points of 5.1, 5.6, 6.0, 6.6, 8.0, and 9.0. The activities were not stimulated by an endogenous activator of the enzyme but were inhibited by EGTA treatment. However, activator-sensitive forms of the enzyme could be separated from brain if the preparation of rat cerebrum was dialyzed against an EGTA containing buffer prior to electrofocusing. The procedure was also used to isolate a column fraction that stimulated maximum velocities of cyclic AMP and cyclic GMP hydrolysis. This fraction was itself devoid of phosphodiesterase activity and had an isoelectric point of 4.7.", "contents": "Isolation of an activator of multiple forms of cyclic nucleotides phosphodiesterase of rat cerebrum by isoelectric focusing. An isoelectric focusing technique was used to isolate multiple forms of cyclic nucleotide phosphodiesterase from a 105 000 times g soluble supernatant fraction of sonicated rat cerebrum. These separated peaks of activity had iso-electric points of 5.1, 5.6, 6.0, 6.6, 8.0, and 9.0. The activities were not stimulated by an endogenous activator of the enzyme but were inhibited by EGTA treatment. However, activator-sensitive forms of the enzyme could be separated from brain if the preparation of rat cerebrum was dialyzed against an EGTA containing buffer prior to electrofocusing. The procedure was also used to isolate a column fraction that stimulated maximum velocities of cyclic AMP and cyclic GMP hydrolysis. This fraction was itself devoid of phosphodiesterase activity and had an isoelectric point of 4.7."} {"id": "PMID:167833", "title": "Characterization of human alpha-galactosidase A and B before and after neuraminidase treatment.", "content": "It has been previously reported that following neuraminidase treatment alpha-galactosidase A is converted into the B form, as revealed by electrophoresis. By a variety of techniques such as isoelectrofocusing, DEAE-chromatography and by enzyme kinetic parameters, no conversion of alpha-galactosidase A into B, or the reverse, could be detected after neuraminidase treatment. Only an apparent transformation of alpha-galactosidase A into B was revealed by Cellogel electrophoresis. In addition, a discrepancy was noticed between the pattern of electrophoretic migration on starch gel and Cellogel and the net electrical charges of the two alpha-galactosidases as deduced by isoelectrofocusing and DEAE-cellulose. Neuraminidase treatment did not affect the activity of alpha-galactosidase A towards the natural substrate, ceramidetrihexoside, but the activity of alpha-galactosidase B decreased by about 30% under the same conditions. The two forms of alpha-galactosidases A and B used in this study were extensively purified by classical procedures.", "contents": "Characterization of human alpha-galactosidase A and B before and after neuraminidase treatment. It has been previously reported that following neuraminidase treatment alpha-galactosidase A is converted into the B form, as revealed by electrophoresis. By a variety of techniques such as isoelectrofocusing, DEAE-chromatography and by enzyme kinetic parameters, no conversion of alpha-galactosidase A into B, or the reverse, could be detected after neuraminidase treatment. Only an apparent transformation of alpha-galactosidase A into B was revealed by Cellogel electrophoresis. In addition, a discrepancy was noticed between the pattern of electrophoretic migration on starch gel and Cellogel and the net electrical charges of the two alpha-galactosidases as deduced by isoelectrofocusing and DEAE-cellulose. Neuraminidase treatment did not affect the activity of alpha-galactosidase A towards the natural substrate, ceramidetrihexoside, but the activity of alpha-galactosidase B decreased by about 30% under the same conditions. The two forms of alpha-galactosidases A and B used in this study were extensively purified by classical procedures."} {"id": "PMID:167834", "title": "Studies on the heme environment of horse heart ferric cytochrome c. Azide and imidazole complexes of ferric cytochrome c.", "content": "Horse heart ferric cytochrome c was investigated by the following three methods: (I) Light absorption spectrophotometry at 23 degrees C and 77 degrees K; (II) Electron paramagnetic resonance (EPR) spectroscopy at 20 degrees K; (III) Precise equilibrium measurements of ferric cytochrome c with azide and imidazole between 14.43 and 30.90 degrees C. I and II have demonstrated that: (1) Ferric cytochrome c azide and imidazole complexes were in the purely low spin state between 20 degrees K and 23 degrees C; (2) The energy for the three t2g orbitals calculated in one hole formalism shows that azide or imidazole bind to the heme iron in a similar manner to met-hemoglobin azide or imidazole complexes, respectively. III has demonstrated that: (1) The change of standard enthalpy and that of standard entropy were -2.3 kcal/mol and -1.6 cal/mol per degree for the azide complex formation, and -1.4 kcal/mol and 2.9 cal/mol per degree for the imidazole complex formation. (2) A linear relationship between the change of entropy and that of enthalpy was observed for the above data for the cyanide complex formation. The complex formation of ferric cytochrome c was discussed based on the results of X-ray crystallographic studies compared with hemoglobin and myoglobin.", "contents": "Studies on the heme environment of horse heart ferric cytochrome c. Azide and imidazole complexes of ferric cytochrome c. Horse heart ferric cytochrome c was investigated by the following three methods: (I) Light absorption spectrophotometry at 23 degrees C and 77 degrees K; (II) Electron paramagnetic resonance (EPR) spectroscopy at 20 degrees K; (III) Precise equilibrium measurements of ferric cytochrome c with azide and imidazole between 14.43 and 30.90 degrees C. I and II have demonstrated that: (1) Ferric cytochrome c azide and imidazole complexes were in the purely low spin state between 20 degrees K and 23 degrees C; (2) The energy for the three t2g orbitals calculated in one hole formalism shows that azide or imidazole bind to the heme iron in a similar manner to met-hemoglobin azide or imidazole complexes, respectively. III has demonstrated that: (1) The change of standard enthalpy and that of standard entropy were -2.3 kcal/mol and -1.6 cal/mol per degree for the azide complex formation, and -1.4 kcal/mol and 2.9 cal/mol per degree for the imidazole complex formation. (2) A linear relationship between the change of entropy and that of enthalpy was observed for the above data for the cyanide complex formation. The complex formation of ferric cytochrome c was discussed based on the results of X-ray crystallographic studies compared with hemoglobin and myoglobin."} {"id": "PMID:167835", "title": "Primary structure of cytochrome c from the insect Ceratitis capitata.", "content": "The complete amino acid sequence of cytochrome c from the Dipterous Ceratitis capitata (serie Acalypterae) has been determined by combining automatic and manual methods of sequence analysis. No overlaps between positions 79 and 80, 86 and 87, 91 and 92 as well as between 99 and 100 were obtained. The alignment of these peptides was done by homology with other sequences of cytochromes c from insects already described. Comparison with the sequences of cytochromes c of other Diptera studied so far shows three changes (positions 50, 60 and 61, according to vertebrate cytochrome c numeration) from the Acalypteran Drosophila melanogaster and five changes (positions 9, 36, 50, 60 and 61) from that of the Calypteran Haematobia irritans.", "contents": "Primary structure of cytochrome c from the insect Ceratitis capitata. The complete amino acid sequence of cytochrome c from the Dipterous Ceratitis capitata (serie Acalypterae) has been determined by combining automatic and manual methods of sequence analysis. No overlaps between positions 79 and 80, 86 and 87, 91 and 92 as well as between 99 and 100 were obtained. The alignment of these peptides was done by homology with other sequences of cytochromes c from insects already described. Comparison with the sequences of cytochromes c of other Diptera studied so far shows three changes (positions 50, 60 and 61, according to vertebrate cytochrome c numeration) from the Acalypteran Drosophila melanogaster and five changes (positions 9, 36, 50, 60 and 61) from that of the Calypteran Haematobia irritans."} {"id": "PMID:167836", "title": "The demonstration of ferrihemochrome intermediates in heinz body formation following the reduction of oxyhemoglobin A by acetylphenylhydrazone.", "content": "Interaction of acetylphenylhydrazine with oxyhemoglobin A in a hemolysate or in intact red cells resulted in the formation of ferrihemochromes as shown by a characteristic optical spectrum. The same optical spectrum was observed in a suspension of red cell ghosts containing numerous Heinz bodies. Electron paramagnetic resonance of actylphenylhydrazine-incubated red cells disclosed the presence of previously identified reversible ferrihemochromes, which can be reduced to functional hemoglobin, and irreversible ferrihemochromes, which cannot be reduced to functional hemoglobin. (Ferrihemochromes are defined as low spin forms of ferric hemoglobin having heme ligands endogenous to the protein structure). In contrast, only irreversible ferrihemochromes could be observed in ghosts containing Heinz bodies. In addition both optical and magnetic features of sulfhemoglobin were observed in an acetylphenylhydrazine-treated red cell hemolysate. Similar optical features are produced by the interaction of aromatic nitrogen-containg reductants with purified oxyhemoglobin in the presence of (NH4)2S. This reaction is not effected by the presence of catalase, suggesting that H2O2 is not an intermediate of the reaction. It is concluded that the mechanism of action of acetylphenylhydrazine with oxyhemoglobin is two-fold, ultimate reduction to high spin ferric hemoglobin followed by ferrihemochrome formation. Thus it appears that the pathway of denaturation of hemolytic anemias and thalassemia or induced by chemical reagents, entails a common route involving the formation of ferric hemoglobin by a reductive mechanism, followed by reversible ferrihemochromes, irreversible ferrihemochromes, and ultimately, precipitation.", "contents": "The demonstration of ferrihemochrome intermediates in heinz body formation following the reduction of oxyhemoglobin A by acetylphenylhydrazone. Interaction of acetylphenylhydrazine with oxyhemoglobin A in a hemolysate or in intact red cells resulted in the formation of ferrihemochromes as shown by a characteristic optical spectrum. The same optical spectrum was observed in a suspension of red cell ghosts containing numerous Heinz bodies. Electron paramagnetic resonance of actylphenylhydrazine-incubated red cells disclosed the presence of previously identified reversible ferrihemochromes, which can be reduced to functional hemoglobin, and irreversible ferrihemochromes, which cannot be reduced to functional hemoglobin. (Ferrihemochromes are defined as low spin forms of ferric hemoglobin having heme ligands endogenous to the protein structure). In contrast, only irreversible ferrihemochromes could be observed in ghosts containing Heinz bodies. In addition both optical and magnetic features of sulfhemoglobin were observed in an acetylphenylhydrazine-treated red cell hemolysate. Similar optical features are produced by the interaction of aromatic nitrogen-containg reductants with purified oxyhemoglobin in the presence of (NH4)2S. This reaction is not effected by the presence of catalase, suggesting that H2O2 is not an intermediate of the reaction. It is concluded that the mechanism of action of acetylphenylhydrazine with oxyhemoglobin is two-fold, ultimate reduction to high spin ferric hemoglobin followed by ferrihemochrome formation. Thus it appears that the pathway of denaturation of hemolytic anemias and thalassemia or induced by chemical reagents, entails a common route involving the formation of ferric hemoglobin by a reductive mechanism, followed by reversible ferrihemochromes, irreversible ferrihemochromes, and ultimately, precipitation."} {"id": "PMID:167837", "title": "Isolation and partial characterization of the major apolipoprotein component of bovine serum high density lipoprotein.", "content": "The delipidated protein component of bovine serum high density lipoprotein was fractionated by gel filtration on a Sephadex G-150 column (equilibrated with buffer containing 6 M urea) into three fractions: I, II and III. Fractions I and II together constitute 88% of all the protein weight of bovine high density lipoprotein, whereas fraction III accounts for the remaining 12%. Analysis of the fractions by sodium dodecyl sulfate-polyacrylamide electrophoresis reveals that fraction I consists mostly of aggregated forms of fraction II and some higher molecular weight species, probably irreversible aggregates of fraction II. The irreversible aggregates are apparently formed during the delipidation procedure or upon aging of the lipoprotein. The major protein component of the high density bovine lipoprotein is found in fraction II; it has a molecular weight of 27 000 plus or minus 1500 and appears to be homogeneous by several physicochemical criteria. The amino acid composition of fractions I and II are essentially identical; their spectral properties, including absorption, fluorescence, and circular dichroism spectra, are similar; however, fraction I appears to contain traces of oxidized lipid and more secondary alpha-helical organization than fraction II. By comparison with the intact lipoprotein, which contains about 65% of alpha-helical structure, fractions I and II have diminished alpha-helical organization, 55% and 43%, respectively. Fraction III, on sodium dodecyl sulfate-polyacrylamide electrophoresis, separates into two protein bands of equivalent intensity, having molecular weights around 13 000 and 11 000. Fraction III is markedly distinct from the other two, in amino acid composition and spectral properties, especially in its red-shifted fluorescence and very low content of alpha-helical structure. The protein composition of bovine serum high density lipoprotein is compared with recently published results for high density lipoprotein apoproteins of man, chimpanzee, rhesus monkey, pig and rat. Similarities and differences are discussed in terms of possible evolutionary and functional factors.", "contents": "Isolation and partial characterization of the major apolipoprotein component of bovine serum high density lipoprotein. The delipidated protein component of bovine serum high density lipoprotein was fractionated by gel filtration on a Sephadex G-150 column (equilibrated with buffer containing 6 M urea) into three fractions: I, II and III. Fractions I and II together constitute 88% of all the protein weight of bovine high density lipoprotein, whereas fraction III accounts for the remaining 12%. Analysis of the fractions by sodium dodecyl sulfate-polyacrylamide electrophoresis reveals that fraction I consists mostly of aggregated forms of fraction II and some higher molecular weight species, probably irreversible aggregates of fraction II. The irreversible aggregates are apparently formed during the delipidation procedure or upon aging of the lipoprotein. The major protein component of the high density bovine lipoprotein is found in fraction II; it has a molecular weight of 27 000 plus or minus 1500 and appears to be homogeneous by several physicochemical criteria. The amino acid composition of fractions I and II are essentially identical; their spectral properties, including absorption, fluorescence, and circular dichroism spectra, are similar; however, fraction I appears to contain traces of oxidized lipid and more secondary alpha-helical organization than fraction II. By comparison with the intact lipoprotein, which contains about 65% of alpha-helical structure, fractions I and II have diminished alpha-helical organization, 55% and 43%, respectively. Fraction III, on sodium dodecyl sulfate-polyacrylamide electrophoresis, separates into two protein bands of equivalent intensity, having molecular weights around 13 000 and 11 000. Fraction III is markedly distinct from the other two, in amino acid composition and spectral properties, especially in its red-shifted fluorescence and very low content of alpha-helical structure. The protein composition of bovine serum high density lipoprotein is compared with recently published results for high density lipoprotein apoproteins of man, chimpanzee, rhesus monkey, pig and rat. Similarities and differences are discussed in terms of possible evolutionary and functional factors."} {"id": "PMID:167838", "title": "Self-association of the major protein component of bovine serum high density lipoprotein.", "content": "The major protein component of bovine high density lipoprotein was investigated in solution by fluorescence polarization and ultracentrifugal techniques. A fluorescent derivative of this protein with 1-dimethylaminonaphthalene-5-sulfonyl chloride was employed in the fluorescence experiments. Over the concentration range from 5-10(-7) M to 5-10(-4) M of the protein monomer at pH values from 2 to 11 and ionic strengths from 0.03 to 2.0, at 23 degrees C, the major protein of bovine high density lipoproteinapoprotein (Apo-HOL-I) was found to exist in a stable aggregated form. The aggregate was not affected by dioxane additions of up to 20% nor by Triton X-100 to 0.2%, but dissociated readily in the presence of 0.07% sodium dodecylsulfate or 6 M urea. At concentrations below 5-10(-7) M, dissociation of the protein aggregate started spontaneously and continued down to 10(-8) M, the lowest measurable concentration. Several physiocochemical properties of the major protein of bovine high density lipoprotein were determined in the stable aggregate form. Molecular weight was 104 000 from ultracentrifugal analysis and 80 000 from gel-filtration. Rotational relaxation time was 115 ns at 25 degrees C, and s-0 20,w was 4.78 s. The results suggest very strong protein-protein interactions (Kd less than 10(-7) M) that are not electrostatic in nature. Hydrophobic interactions of a magnitude that could be affected by 20% dioxane or 0.2% Triton X-100 detergent are also excluded. There is saturation of the interaction sites by the aggregation of a few protein monomer units possibly to form a tetramer which is moderately asymmetric (1:4 axial ratio, assuming an ellipsoid of revolution) and relatively rigid. The strong protein-protein interactions in this pure apolipoprotein suggest the possibility of competition of inter-protein associations with protein-lipid interactions in in vitro lipid binding or lipoprotein reconstitution experiments.", "contents": "Self-association of the major protein component of bovine serum high density lipoprotein. The major protein component of bovine high density lipoprotein was investigated in solution by fluorescence polarization and ultracentrifugal techniques. A fluorescent derivative of this protein with 1-dimethylaminonaphthalene-5-sulfonyl chloride was employed in the fluorescence experiments. Over the concentration range from 5-10(-7) M to 5-10(-4) M of the protein monomer at pH values from 2 to 11 and ionic strengths from 0.03 to 2.0, at 23 degrees C, the major protein of bovine high density lipoproteinapoprotein (Apo-HOL-I) was found to exist in a stable aggregated form. The aggregate was not affected by dioxane additions of up to 20% nor by Triton X-100 to 0.2%, but dissociated readily in the presence of 0.07% sodium dodecylsulfate or 6 M urea. At concentrations below 5-10(-7) M, dissociation of the protein aggregate started spontaneously and continued down to 10(-8) M, the lowest measurable concentration. Several physiocochemical properties of the major protein of bovine high density lipoprotein were determined in the stable aggregate form. Molecular weight was 104 000 from ultracentrifugal analysis and 80 000 from gel-filtration. Rotational relaxation time was 115 ns at 25 degrees C, and s-0 20,w was 4.78 s. The results suggest very strong protein-protein interactions (Kd less than 10(-7) M) that are not electrostatic in nature. Hydrophobic interactions of a magnitude that could be affected by 20% dioxane or 0.2% Triton X-100 detergent are also excluded. There is saturation of the interaction sites by the aggregation of a few protein monomer units possibly to form a tetramer which is moderately asymmetric (1:4 axial ratio, assuming an ellipsoid of revolution) and relatively rigid. The strong protein-protein interactions in this pure apolipoprotein suggest the possibility of competition of inter-protein associations with protein-lipid interactions in in vitro lipid binding or lipoprotein reconstitution experiments."} {"id": "PMID:167839", "title": "Effects of local anesthetics on membrane properties. II. Enhancement of the susceptibility of mammalian cells to agglutination by plant lectins.", "content": "Treatment of untransformed mouse and hamster cells with the tertiary amine local anesthetics dibucaine, tetracaine and procaine increases their susceptibility to agglutination by low doses of the plant lectin concanavalin A. Agglutination of anesthetic-treated untransformed cells by low doses of concanavalin A is accompanied by redistribution of concanavalin A receptors on the cell surface to form patches, similar to that occurring in spontaneous agglutination of virus-transformed cells by concanavalin A. Immunofluorescence and freeze-fracture electronmicroscopic observations indicate that local anesthetics per se do not induce this redistribution of concanavalin A receptors but modify the plasma membrane so that receptor redistribution is facilitated on binding of concanavalin A to the cell surface. Fluorescence polarization measurements on the rotational freedom of the membrane-associated probe, diphenylhexatriene, indicate that local anesthetics produce a small increase in the fluidity of membrane lipids. Spontaneous agglutination of transformed cells by low doses of concanavalin A is inhibited by colchicine and vinblastine but these alkaloids have no effect on concanavalin A agglutination of anesthetic-treated cells. Evidence is presented which suggests that local anesthetics may impair membrane peripheral proteins sensitive to colchicine (microtubules) and cytochalasin-B (microfilaments). Combined treatment of untransformed 3T3 cells with colchicine and cytochalasin B mimics the effect of local anesthetics in enhancing susceptibility to agglutination by low doses of concanavalin A. A hypothesis is presented on the respective roles of colchicine-sensitive and cytochalasin B-sensitive peripheral membrane proteins in controlling the topographical distribution of lectin receptors on the cell surface.", "contents": "Effects of local anesthetics on membrane properties. II. Enhancement of the susceptibility of mammalian cells to agglutination by plant lectins. Treatment of untransformed mouse and hamster cells with the tertiary amine local anesthetics dibucaine, tetracaine and procaine increases their susceptibility to agglutination by low doses of the plant lectin concanavalin A. Agglutination of anesthetic-treated untransformed cells by low doses of concanavalin A is accompanied by redistribution of concanavalin A receptors on the cell surface to form patches, similar to that occurring in spontaneous agglutination of virus-transformed cells by concanavalin A. Immunofluorescence and freeze-fracture electronmicroscopic observations indicate that local anesthetics per se do not induce this redistribution of concanavalin A receptors but modify the plasma membrane so that receptor redistribution is facilitated on binding of concanavalin A to the cell surface. Fluorescence polarization measurements on the rotational freedom of the membrane-associated probe, diphenylhexatriene, indicate that local anesthetics produce a small increase in the fluidity of membrane lipids. Spontaneous agglutination of transformed cells by low doses of concanavalin A is inhibited by colchicine and vinblastine but these alkaloids have no effect on concanavalin A agglutination of anesthetic-treated cells. Evidence is presented which suggests that local anesthetics may impair membrane peripheral proteins sensitive to colchicine (microtubules) and cytochalasin-B (microfilaments). Combined treatment of untransformed 3T3 cells with colchicine and cytochalasin B mimics the effect of local anesthetics in enhancing susceptibility to agglutination by low doses of concanavalin A. A hypothesis is presented on the respective roles of colchicine-sensitive and cytochalasin B-sensitive peripheral membrane proteins in controlling the topographical distribution of lectin receptors on the cell surface."} {"id": "PMID:167840", "title": "Bile salt alteration of ion transport across jejunal mucosa.", "content": "The effect of conjugated dihydroxy and trihydroxy bile salts on electrolyte transport across isolated rabbit jejunal mucosa was studied. Both taurochenodeoxycholic acid and taurocholic acid increased the short-circuit current (Isc) in bicarbonate-Ringer solution but not in a bicarbonate-free, chloride-free solution. Taurochenodeoxycholic acid was significantly more effective than taurocholic acid in increasing Isc. The presence of theophylline prevented the taurochenodeoxycholic acid- and taurocholic acid-induced increase in Isc. Transmural ion fluxes across jejunal mucosa demonstrated that 2 mM taurochenodeoxycholic acid decreased net Na+ absorption, increased net Cl- secretion and increased the residual flux (which probably represents HCO3- secretion). These studies support the hypothesis that cyclic AMP may be a mediator of intestinal electrolyte secretion.", "contents": "Bile salt alteration of ion transport across jejunal mucosa. The effect of conjugated dihydroxy and trihydroxy bile salts on electrolyte transport across isolated rabbit jejunal mucosa was studied. Both taurochenodeoxycholic acid and taurocholic acid increased the short-circuit current (Isc) in bicarbonate-Ringer solution but not in a bicarbonate-free, chloride-free solution. Taurochenodeoxycholic acid was significantly more effective than taurocholic acid in increasing Isc. The presence of theophylline prevented the taurochenodeoxycholic acid- and taurocholic acid-induced increase in Isc. Transmural ion fluxes across jejunal mucosa demonstrated that 2 mM taurochenodeoxycholic acid decreased net Na+ absorption, increased net Cl- secretion and increased the residual flux (which probably represents HCO3- secretion). These studies support the hypothesis that cyclic AMP may be a mediator of intestinal electrolyte secretion."} {"id": "PMID:167842", "title": "Interaction of lysine-rich histone and DNA in chromatin structure.", "content": "The heat denaturation and renaturation curves of rat liver and ascites hepatoma (AH 108A) chromatins were measured. In these renaturation curves, there are small sigmoidal regions. These sigmoidal regions remained in redenaturation curves and were largely stable to DNAase I digestion. When the chromatins were treated stepwise with NaClO4 and lysine-rich histones were removed, the sigmoidal regions in the renaturation curves disappeared. These results suggested that the sigmoidal regions reflected the interaction of DNA and lysine-rich histones.", "contents": "Interaction of lysine-rich histone and DNA in chromatin structure. The heat denaturation and renaturation curves of rat liver and ascites hepatoma (AH 108A) chromatins were measured. In these renaturation curves, there are small sigmoidal regions. These sigmoidal regions remained in redenaturation curves and were largely stable to DNAase I digestion. When the chromatins were treated stepwise with NaClO4 and lysine-rich histones were removed, the sigmoidal regions in the renaturation curves disappeared. These results suggested that the sigmoidal regions reflected the interaction of DNA and lysine-rich histones."} {"id": "PMID:167843", "title": "Non-histone chromosomal proteins from virus-transformed and untransformed 3T3 mouse fibroblasts.", "content": "A peak in the non-histone chromosomal protein polyacrylamide gel electrophoresis profiles has been detected which is higher in log phase 3T3 and 3T3/SV40 cells than in density-inhibited 3T3 cells. Radioactive incorporation is substantially higher into this peak in log phase 3T3 than in 3T3/SV40 and density-inhibited 3T3 cells. Reversion of 3T3/SV40 cells with dibutyryl cyclic AMP and theophylline produces increased radioactive incorporation into the peak. Electrophoresis of non-histone chromosomal proteins extracted at different stages of the cell cycle in density inhibited 3T3 cells following serum stimulation shows a cyclic variation in the amount of this peak with maximum accumulation in late G1. In contrast the height of an equivalent peak in synchronously growing 3T3/SV40 cells remains constant throughout the cell cycle. It is postulated that the protein(s) of this peak may have a regulatory role in cell growth.", "contents": "Non-histone chromosomal proteins from virus-transformed and untransformed 3T3 mouse fibroblasts. A peak in the non-histone chromosomal protein polyacrylamide gel electrophoresis profiles has been detected which is higher in log phase 3T3 and 3T3/SV40 cells than in density-inhibited 3T3 cells. Radioactive incorporation is substantially higher into this peak in log phase 3T3 than in 3T3/SV40 and density-inhibited 3T3 cells. Reversion of 3T3/SV40 cells with dibutyryl cyclic AMP and theophylline produces increased radioactive incorporation into the peak. Electrophoresis of non-histone chromosomal proteins extracted at different stages of the cell cycle in density inhibited 3T3 cells following serum stimulation shows a cyclic variation in the amount of this peak with maximum accumulation in late G1. In contrast the height of an equivalent peak in synchronously growing 3T3/SV40 cells remains constant throughout the cell cycle. It is postulated that the protein(s) of this peak may have a regulatory role in cell growth."} {"id": "PMID:167844", "title": "DNA synthesis in L-cells in the presence of 5-fluorodeoxyuridine.", "content": "After 16 h of incubation with 10-minus6 M FdUrd, the rate of (32P) orthophosphate uptake into DNA isolated from L-cells amounted to 15% of that of an untreated culture, although cell division had stopped several hours earlier. All 4 deoxynucleotides were present in this DNA but its nucleotide composition, as measured by enzymatic digestion and chromatography, reflected a decreased thymidine precursor pool in FdUrd-treated cells. Sedimentation analysis in alkaline sucrose gradients revealed that the DNA formed in the presence of FdUrd had a sedimentation coefficient of 10 S which corresponded to a single-stranded molecular weight of 5.5.105. This DNA could be \"chased\" into a high molecular weight DNA if the FdUrd block was bypassed with added dThd or BrdUrd. Other analyses failed to detect RNA covalently linked to the DNA fragments at a level of more than 5% RNA or about 90 ribonucleotides. The accumulation of these DNA fragments could be explained by assuming that in the presence of limiting precursor pool the rate of DNA chain initiation is greater than the rate of chain elongation.", "contents": "DNA synthesis in L-cells in the presence of 5-fluorodeoxyuridine. After 16 h of incubation with 10-minus6 M FdUrd, the rate of (32P) orthophosphate uptake into DNA isolated from L-cells amounted to 15% of that of an untreated culture, although cell division had stopped several hours earlier. All 4 deoxynucleotides were present in this DNA but its nucleotide composition, as measured by enzymatic digestion and chromatography, reflected a decreased thymidine precursor pool in FdUrd-treated cells. Sedimentation analysis in alkaline sucrose gradients revealed that the DNA formed in the presence of FdUrd had a sedimentation coefficient of 10 S which corresponded to a single-stranded molecular weight of 5.5.105. This DNA could be \"chased\" into a high molecular weight DNA if the FdUrd block was bypassed with added dThd or BrdUrd. Other analyses failed to detect RNA covalently linked to the DNA fragments at a level of more than 5% RNA or about 90 ribonucleotides. The accumulation of these DNA fragments could be explained by assuming that in the presence of limiting precursor pool the rate of DNA chain initiation is greater than the rate of chain elongation."} {"id": "PMID:167845", "title": "A cell-free mammalian protein-synthesizing system stimulated by RNA from avian myeloblastosis virus.", "content": "Carcinoma cells, oncornavirus-infected cells and fetal bovine tissue provide salt wash ribosomal factors capable of responding to avian myeloblastosis virus (AM virus)-RNA and stimulating the incorporation of amino acids into proteins as well as catalyzing the binding of N-acetylated (35S) methionyl-tRNA. The exogenously dependent amino acid incorporation system is stimulated by the high molecular weight species of AM virus-RNA only, particularly the fraction containing polyadenylate (poly(A)) residues; the system is also markedly inhibited by the low molecular weight AM virus-RNA species. Activity for the exogenous system displays very definite divalent/monovalent cation optima and requires the presence of mammalian transfer RNA.", "contents": "A cell-free mammalian protein-synthesizing system stimulated by RNA from avian myeloblastosis virus. Carcinoma cells, oncornavirus-infected cells and fetal bovine tissue provide salt wash ribosomal factors capable of responding to avian myeloblastosis virus (AM virus)-RNA and stimulating the incorporation of amino acids into proteins as well as catalyzing the binding of N-acetylated (35S) methionyl-tRNA. The exogenously dependent amino acid incorporation system is stimulated by the high molecular weight species of AM virus-RNA only, particularly the fraction containing polyadenylate (poly(A)) residues; the system is also markedly inhibited by the low molecular weight AM virus-RNA species. Activity for the exogenous system displays very definite divalent/monovalent cation optima and requires the presence of mammalian transfer RNA."} {"id": "PMID:167846", "title": "The oxidation of tiron by superoxide anion. Kinetics of the reaction in aqueous solution in chloroplasts.", "content": "The rate of reaction between superoxide anion (O2) and 1,2-dihydroxybenzene-3,5-disulfonic acid (tiron) was measured with pulse radiolysis-generated O2. A kinetic spectrophotometric method utilizing competition between p-benzoquinone and tiron for O2 was employed. In this system, the known rate of reduction of p-benzoquinone was compared with the rate of oxidation of tiron to the semiquinone. From the concentration dependence of the rate of tiron oxidation, the absolute second order rate constant for the reaction was determined to be 5x10-8 M-minus1-s-minus1. Ascorbate reduced O2 to hydrogen peroxide with a rate constant of 10-8 M-minus1-s-minus1 as determined by the same method. The tiron semiquinone may be used as an indicator free radical for the formation of superoxide anion in biological systems because of the rapid rate of oxidation of the catechol by O2 compared to the rate of O2 formation is most enzymatic systems. Tiron oxidation was used to follow the formation of superoxide anion in swollen chloroplasts. The chloroplasts photochemically reduced molecular oxygen which was further reduced to hydrogen peroxide by tiron. Tiron oxidation specifically required O2 since O2 was consumed in the reaction and tiron did not reduce the P700 cation radical or other components of Photosystem I under anaerobic conditions.", "contents": "The oxidation of tiron by superoxide anion. Kinetics of the reaction in aqueous solution in chloroplasts. The rate of reaction between superoxide anion (O2) and 1,2-dihydroxybenzene-3,5-disulfonic acid (tiron) was measured with pulse radiolysis-generated O2. A kinetic spectrophotometric method utilizing competition between p-benzoquinone and tiron for O2 was employed. In this system, the known rate of reduction of p-benzoquinone was compared with the rate of oxidation of tiron to the semiquinone. From the concentration dependence of the rate of tiron oxidation, the absolute second order rate constant for the reaction was determined to be 5x10-8 M-minus1-s-minus1. Ascorbate reduced O2 to hydrogen peroxide with a rate constant of 10-8 M-minus1-s-minus1 as determined by the same method. The tiron semiquinone may be used as an indicator free radical for the formation of superoxide anion in biological systems because of the rapid rate of oxidation of the catechol by O2 compared to the rate of O2 formation is most enzymatic systems. Tiron oxidation was used to follow the formation of superoxide anion in swollen chloroplasts. The chloroplasts photochemically reduced molecular oxygen which was further reduced to hydrogen peroxide by tiron. Tiron oxidation specifically required O2 since O2 was consumed in the reaction and tiron did not reduce the P700 cation radical or other components of Photosystem I under anaerobic conditions."} {"id": "PMID:167847", "title": "Electron transport in the membrane of lutoids from the latex of Hevea brasiliensis.", "content": "1. An antimycin-insensitive NADH-cytochrome c oxidoreductase (E.C. 1.6.99.3) activity can be demonstrated in the membrane of lutoids isolated from the latex of Hevea brasiliensis. This electron transport system can also use ferricyanide as an electron acceptor, but is unable to oxidize NADPH. 2. Two beta-type cytochromes are present in the membranes. Cytochrome beta563 is partially reduced by NADH and ascorbate, but is not reducible by NADPH. It shows a double peak at 555 and 561 nm at 77 degrees K. A second cytochrome, cytochrome beta561, seems to be reducible by hydrosulfite only. 3. In the reduced state, these cytochromes do not combine with CO. The occurrence of cytochrome P-450 could not be demonstrated. 4. The role of the NADH oxidation system is considered in relation to the biosynthesis of polyisoprene compounds in the latex.", "contents": "Electron transport in the membrane of lutoids from the latex of Hevea brasiliensis. 1. An antimycin-insensitive NADH-cytochrome c oxidoreductase (E.C. 1.6.99.3) activity can be demonstrated in the membrane of lutoids isolated from the latex of Hevea brasiliensis. This electron transport system can also use ferricyanide as an electron acceptor, but is unable to oxidize NADPH. 2. Two beta-type cytochromes are present in the membranes. Cytochrome beta563 is partially reduced by NADH and ascorbate, but is not reducible by NADPH. It shows a double peak at 555 and 561 nm at 77 degrees K. A second cytochrome, cytochrome beta561, seems to be reducible by hydrosulfite only. 3. In the reduced state, these cytochromes do not combine with CO. The occurrence of cytochrome P-450 could not be demonstrated. 4. The role of the NADH oxidation system is considered in relation to the biosynthesis of polyisoprene compounds in the latex."} {"id": "PMID:167848", "title": "Energy-linked and energy-independent transhydrogenase activities in Escherichia coli vesicles.", "content": "Active transport vesicles of Escherichia coli were shown to possess low levels of energy-independent and energy-dependent nicotinamide nucleotide transhydrogenase activities. Breakage of such vesicles in a French pressure cell resulted in a fraction which had an 8-10-fold increased respiration- and ATP-driven transhydrogenase activities. Stimulation of the ATPase activity in vesicles with Triton X-100 was also paralledled by a 2-fold increase in the energy-independent transhydrogenase. Disruption of the vesicles similarly resulted in increases in the energy-independent transhydrogenase, NADH and succinate oxidase activities but a decrease in succinate supported proline uptake. In the light of these findings, the \"sidedness' of the vesicle membranes is discussed.", "contents": "Energy-linked and energy-independent transhydrogenase activities in Escherichia coli vesicles. Active transport vesicles of Escherichia coli were shown to possess low levels of energy-independent and energy-dependent nicotinamide nucleotide transhydrogenase activities. Breakage of such vesicles in a French pressure cell resulted in a fraction which had an 8-10-fold increased respiration- and ATP-driven transhydrogenase activities. Stimulation of the ATPase activity in vesicles with Triton X-100 was also paralledled by a 2-fold increase in the energy-independent transhydrogenase. Disruption of the vesicles similarly resulted in increases in the energy-independent transhydrogenase, NADH and succinate oxidase activities but a decrease in succinate supported proline uptake. In the light of these findings, the \"sidedness' of the vesicle membranes is discussed."} {"id": "PMID:167849", "title": "Two electron donation sites for exogenous reductants in chloroplast photosystem II.", "content": "Two sites are distinguished for the oxidation of exogenous donors by Photosystem II in non-oxygen evolving chloroplasts. In the presence of lipophilic donors (e.g. phenylenediamine, benzidine, diphenylcarbazide), the rate for Signal IIf rereduction following a flash increases as the concentration of exogenous reductant increases. There is a decrease (20-40%) in Signal IIf magnitude accompanying donor addition at low (smaller than 10(-%) M) concentrations, but the extent of the decrease does not change further with increasing donor concentrations. Complementary polarographic experiments monitoring donor (phenylenediamine) oxidation show an increase in oxidation rate with increasing donor concentration. In the presence of the hydrophilic donor, Mn-2+, the Signal IIf decay halftime remains constant with increasing Mn-2+ concentration. However, the flash-induced Signal IIf magnitude pregressively decreases with increasing Mn-2+ concentration. These results are interpreted in terms of two competing paths for the reduction of P680+. In one path P680+ reduction is accompanied by the appearance of Signal IIf, and lipophilic donors subsequently rereduce the Signal IIf species in a series reaction. This reduction follows pseudo-first order kinetics as a function of donor concentration. In the second path Mn-2+ reduces P680+ in a parallel reaction that competes with the formation of the Signal IIf species. This results in a decrease in the magnitude of Signal IIf, but no change in its decay time.", "contents": "Two electron donation sites for exogenous reductants in chloroplast photosystem II. Two sites are distinguished for the oxidation of exogenous donors by Photosystem II in non-oxygen evolving chloroplasts. In the presence of lipophilic donors (e.g. phenylenediamine, benzidine, diphenylcarbazide), the rate for Signal IIf rereduction following a flash increases as the concentration of exogenous reductant increases. There is a decrease (20-40%) in Signal IIf magnitude accompanying donor addition at low (smaller than 10(-%) M) concentrations, but the extent of the decrease does not change further with increasing donor concentrations. Complementary polarographic experiments monitoring donor (phenylenediamine) oxidation show an increase in oxidation rate with increasing donor concentration. In the presence of the hydrophilic donor, Mn-2+, the Signal IIf decay halftime remains constant with increasing Mn-2+ concentration. However, the flash-induced Signal IIf magnitude pregressively decreases with increasing Mn-2+ concentration. These results are interpreted in terms of two competing paths for the reduction of P680+. In one path P680+ reduction is accompanied by the appearance of Signal IIf, and lipophilic donors subsequently rereduce the Signal IIf species in a series reaction. This reduction follows pseudo-first order kinetics as a function of donor concentration. In the second path Mn-2+ reduces P680+ in a parallel reaction that competes with the formation of the Signal IIf species. This results in a decrease in the magnitude of Signal IIf, but no change in its decay time."} {"id": "PMID:167850", "title": "Nature of photochemical reactions in chromatophores of Chromatium D. III. Heterogeneity of the photosynthetic units.", "content": "The effect of isooctane extraction on photooxidation of c-type cytochromes was investigated in Chromatium chromatophores. Photooxidation of cytochrome c-555 was not affected by isooctane-extraction was abolished by thorough extraction of ubiquinone-7, but the quantum yield of the cytochrome photooxidation remained unchanged until 90% of the total ubiquinone was extracted. The photooxidation of cytochrome c-552 was recovered by the addition of ubiquinone-7 but not by menaquinone. A dark incubation of sufficient length was needed for maximal quantum yield of cytochrome c-555 photooxidation in the presence of 30 mM ascorbate. It is proposed that there are two types of photosynthetic units (or associations of molecules involved in the primary redox reactions) in Chromatium chromatophores. The combinations of primary electron donor-reaction center chlorophyll-primary electron acceptor may be cytochrome c-552-P890=ubiquinone in one type and cytochrome c-555-P890-X in another.", "contents": "Nature of photochemical reactions in chromatophores of Chromatium D. III. Heterogeneity of the photosynthetic units. The effect of isooctane extraction on photooxidation of c-type cytochromes was investigated in Chromatium chromatophores. Photooxidation of cytochrome c-555 was not affected by isooctane-extraction was abolished by thorough extraction of ubiquinone-7, but the quantum yield of the cytochrome photooxidation remained unchanged until 90% of the total ubiquinone was extracted. The photooxidation of cytochrome c-552 was recovered by the addition of ubiquinone-7 but not by menaquinone. A dark incubation of sufficient length was needed for maximal quantum yield of cytochrome c-555 photooxidation in the presence of 30 mM ascorbate. It is proposed that there are two types of photosynthetic units (or associations of molecules involved in the primary redox reactions) in Chromatium chromatophores. The combinations of primary electron donor-reaction center chlorophyll-primary electron acceptor may be cytochrome c-552-P890=ubiquinone in one type and cytochrome c-555-P890-X in another."} {"id": "PMID:167851", "title": "Stereochemistry of the hydrogen transfer to NAD catalyzed by D-galactose dehydrogenase from Pseudomonas fluorescens.", "content": "The stereochemistry of the hydrogen transfer to NAD catalyzed by D-galactose dehydrogenase (E.C. 1.1.1.48) from P. fluorescens was investigated. The label at C-1 of D-[1--3H] galactose was enzymatically transferred to NAD and the resulting [4--3H]NADH was isolated and its stereochemistry at C-4 investigated. It was found that the label was exclusively located at the 4(S) position in NADH which calls for classification as a B-enzyme. This result was confirmed by an alternate approach in which [4--3H]NAD was reduced by D-galactose as catalyzed by D-galactose dehydrogenase. The sterochemistry at C-4 of the nicotinamide ring would then have to opposite to that in the first experiment. As expected, the label was now exclusively located in the 4(R) position, again confirming the B-calssification of the enzyme.", "contents": "Stereochemistry of the hydrogen transfer to NAD catalyzed by D-galactose dehydrogenase from Pseudomonas fluorescens. The stereochemistry of the hydrogen transfer to NAD catalyzed by D-galactose dehydrogenase (E.C. 1.1.1.48) from P. fluorescens was investigated. The label at C-1 of D-[1--3H] galactose was enzymatically transferred to NAD and the resulting [4--3H]NADH was isolated and its stereochemistry at C-4 investigated. It was found that the label was exclusively located at the 4(S) position in NADH which calls for classification as a B-enzyme. This result was confirmed by an alternate approach in which [4--3H]NAD was reduced by D-galactose as catalyzed by D-galactose dehydrogenase. The sterochemistry at C-4 of the nicotinamide ring would then have to opposite to that in the first experiment. As expected, the label was now exclusively located in the 4(R) position, again confirming the B-calssification of the enzyme."} {"id": "PMID:167852", "title": "Differentiation of fluorides-stimulated and non-fluoride-stimulated components of beef brain cortex adenylate cyclase cy calcium ions, ethyleneglycol-bis-(beta-aminoethyl ether) N,N'-tetraacetic acid and Triton X-100.", "content": "Beef brain cortex adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) activity is 84--88% inhibited by 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid in the absence of F- but only 50--60% inhibited by 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid in the presence of F-. In either case, further increase in EGTA concentration did not alter the degree of inhibition. The inhibition can be completely reversed in both cases by addition of 3 - 10(-5) M Ca2+, (yielding a [free Ca2+] of approximately 2 - 10(-6) M) and 5 - 10(-5) M Mn2+ or Co2+ and partially by 5 - 10(-5) M Sr2+ but not by addition of 5 - 10(-5) M Ba2+, Zn2+, Ni2+ or Fe2+. A [free Ca2+] of 7.2 - 10(-5) M markedly inhibited cyclase activity in the presence of F-. Solubilization by 1.8% Triton X-100 resulted in an enzyme preparation no longer stimulated by NaF and 100% inhibited by the addition of 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid either in the absence or presence of NaF. However, in contrast to ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-TETRAACETIC ACID, EDTA had no measurable effect on adenylate cyclase either in the presence or absence of NaF and ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid did not affect ATPase or phosphodiesterase activities. The data is rationalized by the postulation of two independent enzyme components in brain cortex: one component is about six-fold activated by NaF and the NaF effect is enhanced by low concentrations of Ca2+ and Mg2+. A second component is totally Ca2+ dependent and inhibited by high concentrations of F-. Mn2+, Co2+ and Sr2+ appear to be in vitro Ca2+ substitutes for both enzyme systems. On this basis, Triton X-100 treatment results in about a three-fold increase in specific activity of the Ca2+ dependent cyclase component but a complete abolition of the NaF stimulated component.", "contents": "Differentiation of fluorides-stimulated and non-fluoride-stimulated components of beef brain cortex adenylate cyclase cy calcium ions, ethyleneglycol-bis-(beta-aminoethyl ether) N,N'-tetraacetic acid and Triton X-100. Beef brain cortex adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) activity is 84--88% inhibited by 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid in the absence of F- but only 50--60% inhibited by 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid in the presence of F-. In either case, further increase in EGTA concentration did not alter the degree of inhibition. The inhibition can be completely reversed in both cases by addition of 3 - 10(-5) M Ca2+, (yielding a [free Ca2+] of approximately 2 - 10(-6) M) and 5 - 10(-5) M Mn2+ or Co2+ and partially by 5 - 10(-5) M Sr2+ but not by addition of 5 - 10(-5) M Ba2+, Zn2+, Ni2+ or Fe2+. A [free Ca2+] of 7.2 - 10(-5) M markedly inhibited cyclase activity in the presence of F-. Solubilization by 1.8% Triton X-100 resulted in an enzyme preparation no longer stimulated by NaF and 100% inhibited by the addition of 5 - 10(-5) M ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid either in the absence or presence of NaF. However, in contrast to ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-TETRAACETIC ACID, EDTA had no measurable effect on adenylate cyclase either in the presence or absence of NaF and ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid did not affect ATPase or phosphodiesterase activities. The data is rationalized by the postulation of two independent enzyme components in brain cortex: one component is about six-fold activated by NaF and the NaF effect is enhanced by low concentrations of Ca2+ and Mg2+. A second component is totally Ca2+ dependent and inhibited by high concentrations of F-. Mn2+, Co2+ and Sr2+ appear to be in vitro Ca2+ substitutes for both enzyme systems. On this basis, Triton X-100 treatment results in about a three-fold increase in specific activity of the Ca2+ dependent cyclase component but a complete abolition of the NaF stimulated component."} {"id": "PMID:167853", "title": "Stereochemistry of the hydrogen transfer to NAD catalyzed by (S)alanine dehydrogenase from Bacillus subtilis.", "content": "The stereochemistry of the hydrogen transfer to NAD catalyzed by (S)alanine dehydrogenase [ (S)alanine: NAD oxidoreductase (EC 1.4.1.1) ] from B. subtilis was investigated. The label at C-2 of (S) [2,3--3H] alanine was enzymatically transferred to NAD, and the [4--3H]NADH produced isolated and the stereochemistry at C-4 investigated. It was found that the label was exclusively located at the (R) position which indicates that (S)alanine dehydrogenase is an A-type enzyme. This result was confirmed in an alternate way by reducing enzymatically [4--3H]NAD with non labeled (S)alanine and (S)alanine dehydrogenase and investigating the stereochemistry of the ]4--3H]NADH produced. As expected, the label was now exclusively located at the (S) position. This proves that (S)alanine dehydrogenase isolated from B. subtilis should be classified as an A-enzyme with regard to the stereochemistry of the hydrogen transfer to NAD.", "contents": "Stereochemistry of the hydrogen transfer to NAD catalyzed by (S)alanine dehydrogenase from Bacillus subtilis. The stereochemistry of the hydrogen transfer to NAD catalyzed by (S)alanine dehydrogenase [ (S)alanine: NAD oxidoreductase (EC 1.4.1.1) ] from B. subtilis was investigated. The label at C-2 of (S) [2,3--3H] alanine was enzymatically transferred to NAD, and the [4--3H]NADH produced isolated and the stereochemistry at C-4 investigated. It was found that the label was exclusively located at the (R) position which indicates that (S)alanine dehydrogenase is an A-type enzyme. This result was confirmed in an alternate way by reducing enzymatically [4--3H]NAD with non labeled (S)alanine and (S)alanine dehydrogenase and investigating the stereochemistry of the ]4--3H]NADH produced. As expected, the label was now exclusively located at the (S) position. This proves that (S)alanine dehydrogenase isolated from B. subtilis should be classified as an A-enzyme with regard to the stereochemistry of the hydrogen transfer to NAD."} {"id": "PMID:167854", "title": "The intracellular localization of long-chain acyl-CoA synthetase in brown adipose tissue.", "content": "1. The acyl-CoA synthetase activity in brown adipose tissue of cold-exposed guinea pig has been studied by measuring the rate of palmitoylcarnitine formation in the presence of excess carnitine palmitoyltransferase. 2. The rate of palmitoylcarnitine formation in the mitochondria was found to be 161 plus or minus 64 nmol.mg-minus-1. min-minus-1 (n=9). 3. In the absence of added palmitate and bovine serum albumin a total of 35 plus or minus 1 nmol endogenous fatty acids.mg-minus-1 were activated with three different mitochondrial preparations. 4. Three different experimental approaches have been used to study the subcellular localization of the enzyme: (a) conventional differential centrifugation (De Duve, C., Pressman, B.C., Gianetto, R., Wattiaux, R. and Appelmans, F. (1955) Biochem. J. 60, 604-617) (B) the determination of the sediterm of different marker enzymes (Slinde, E. and Flatmark. T. (1973) Anal. Biochem. 56, 324-340) and (c) the determination of the stoichiometry between the activities of these enzymes sedimented at higher centrifugal effects. 5. Throughout all fractionation procedures, the long-chain acyl-CoA synthetase follows strictly the amine oxidase generally considered to be exclusively located on the mitochondrial outer membrane.", "contents": "The intracellular localization of long-chain acyl-CoA synthetase in brown adipose tissue. 1. The acyl-CoA synthetase activity in brown adipose tissue of cold-exposed guinea pig has been studied by measuring the rate of palmitoylcarnitine formation in the presence of excess carnitine palmitoyltransferase. 2. The rate of palmitoylcarnitine formation in the mitochondria was found to be 161 plus or minus 64 nmol.mg-minus-1. min-minus-1 (n=9). 3. In the absence of added palmitate and bovine serum albumin a total of 35 plus or minus 1 nmol endogenous fatty acids.mg-minus-1 were activated with three different mitochondrial preparations. 4. Three different experimental approaches have been used to study the subcellular localization of the enzyme: (a) conventional differential centrifugation (De Duve, C., Pressman, B.C., Gianetto, R., Wattiaux, R. and Appelmans, F. (1955) Biochem. J. 60, 604-617) (B) the determination of the sediterm of different marker enzymes (Slinde, E. and Flatmark. T. (1973) Anal. Biochem. 56, 324-340) and (c) the determination of the stoichiometry between the activities of these enzymes sedimented at higher centrifugal effects. 5. Throughout all fractionation procedures, the long-chain acyl-CoA synthetase follows strictly the amine oxidase generally considered to be exclusively located on the mitochondrial outer membrane."} {"id": "PMID:167855", "title": "Effects of several common long chain fatty acids on the properties and lipid composition of the very low density lipoprotein secreted by the perfused rat liver.", "content": "1. Livers from normal fed male rats were perfused in vitro with a bloodless medium which contained intially 3% bovine serum albumin and 100 mg% glucose. Albumin alone, or myristate (14 : 0), palmitate (16 : 0), palmitoleate (16 : 1), stearate (18 : 0), oleate (18 : 1), or linoleate (18:2) was infused at a constant rate (496 mumol/4 h), as a complex with albumin, during the experiment. 2. The very low density lipoprotein secreted by the liver after infusion of unsaturated fatty acids (16 : 1, 18 :1, 18 : 2) has a faster rate-zonal mobility in the ultracentrifuge and is, therefore, probably a larger particle with fewer moles of phospholipid and cholesterol relative to triacyglycerol (triacyglycerol/phospholipids/cholesterol = 100/25.1/16.4) than the very low density lipoproteins produced after infusion of saturated (14 : 0, 16 : 0, 18 : 0) fatty acids (triacyglycerol/phospholipids/cholesterol = 100/30.1/19.1). The molar ratio of phosphoipids/cholesterol of the very low density lipoprotein was similar regardless of which fatty acid was infused. The predominant fatty acid of the very low density lipoprotein or hepatic triacyglycerol, in all cases, was the infused acid. 3. We conclude that free fatty acid regulates the quantity and proportions of triacyglycerol, phospholipids, and cholesterol secreted by the liver in the very low density lipoprotein, and therefore, may secondarily influence concentrations of lipids in the very low density lipoprotein and other plasma lipoproteins circulating in vivo.", "contents": "Effects of several common long chain fatty acids on the properties and lipid composition of the very low density lipoprotein secreted by the perfused rat liver. 1. Livers from normal fed male rats were perfused in vitro with a bloodless medium which contained intially 3% bovine serum albumin and 100 mg% glucose. Albumin alone, or myristate (14 : 0), palmitate (16 : 0), palmitoleate (16 : 1), stearate (18 : 0), oleate (18 : 1), or linoleate (18:2) was infused at a constant rate (496 mumol/4 h), as a complex with albumin, during the experiment. 2. The very low density lipoprotein secreted by the liver after infusion of unsaturated fatty acids (16 : 1, 18 :1, 18 : 2) has a faster rate-zonal mobility in the ultracentrifuge and is, therefore, probably a larger particle with fewer moles of phospholipid and cholesterol relative to triacyglycerol (triacyglycerol/phospholipids/cholesterol = 100/25.1/16.4) than the very low density lipoproteins produced after infusion of saturated (14 : 0, 16 : 0, 18 : 0) fatty acids (triacyglycerol/phospholipids/cholesterol = 100/30.1/19.1). The molar ratio of phosphoipids/cholesterol of the very low density lipoprotein was similar regardless of which fatty acid was infused. The predominant fatty acid of the very low density lipoprotein or hepatic triacyglycerol, in all cases, was the infused acid. 3. We conclude that free fatty acid regulates the quantity and proportions of triacyglycerol, phospholipids, and cholesterol secreted by the liver in the very low density lipoprotein, and therefore, may secondarily influence concentrations of lipids in the very low density lipoprotein and other plasma lipoproteins circulating in vivo."} {"id": "PMID:167856", "title": "The effects of hyperlipidemia on lipoprotein metabolism in squirrel monkeys and rabbits.", "content": "We studied the metabolism of different classes of lipoprotein in squirrel monkeys and rabbits. Lipoproteins were labeled in vivo in donor animals with (3H)leucine and (3H)cholesterol. The rate of disappearance from plasma of recipient squirrel monkeys of the protein moiety of the very low density lipoproteins was rapid, that of high density lipoproteins slow, and the rate for low density lipoproteins was intermediate. The fractional turnover of the apoprotein of low density lipoproteins was slightly reduced in hyperlipidemic monkeys, but the absolute rates of synthesis and catabolism were increased. Hyperdipidemia in rabbits resulted in a dramatic reduction in the fractional catabolic rate of low density lipoprotein apoprotein. Hyperlipidemia in the donors of biosynthetic low density lipoproteins also influenced the rates of catabolism in rabbits. We showed the cycloheximide that although there was recycling of (3H)leucine into other proteins, the reutilization of leucine from low density lipoproteins for nascent low density lipoproteins was not significant. In most tissues the ratio of cholesterol:protein radioactivity was much greater than that for plasma 24 h after administration of labeled low density lipoproteins, but the ratios for aortic intima plus inner media and for plasma low density lipoproteins were similar. The presence of atherosclerosis resulted in a large increase in the apparent uptake of low density lipoproteins by the aortas of rabbits and monkeys.", "contents": "The effects of hyperlipidemia on lipoprotein metabolism in squirrel monkeys and rabbits. We studied the metabolism of different classes of lipoprotein in squirrel monkeys and rabbits. Lipoproteins were labeled in vivo in donor animals with (3H)leucine and (3H)cholesterol. The rate of disappearance from plasma of recipient squirrel monkeys of the protein moiety of the very low density lipoproteins was rapid, that of high density lipoproteins slow, and the rate for low density lipoproteins was intermediate. The fractional turnover of the apoprotein of low density lipoproteins was slightly reduced in hyperlipidemic monkeys, but the absolute rates of synthesis and catabolism were increased. Hyperdipidemia in rabbits resulted in a dramatic reduction in the fractional catabolic rate of low density lipoprotein apoprotein. Hyperlipidemia in the donors of biosynthetic low density lipoproteins also influenced the rates of catabolism in rabbits. We showed the cycloheximide that although there was recycling of (3H)leucine into other proteins, the reutilization of leucine from low density lipoproteins for nascent low density lipoproteins was not significant. In most tissues the ratio of cholesterol:protein radioactivity was much greater than that for plasma 24 h after administration of labeled low density lipoproteins, but the ratios for aortic intima plus inner media and for plasma low density lipoproteins were similar. The presence of atherosclerosis resulted in a large increase in the apparent uptake of low density lipoproteins by the aortas of rabbits and monkeys."} {"id": "PMID:167857", "title": "Induction of cystathionase in foetal rat liver explants. Effects of dexamethasone, N-6, O-2 -dibutyryladenosine 3,5 -monophosphate and glucagon in vitro.", "content": "At the 18th day of gestation and thereafter foetal rat liver explants in organ culture showed the competence to respond to dexamethasone by increased cystathionase activity, whereas the ability to respond to dibutyryl cyclic AMP or glucagon became evident at a later developmental stage (during the last 2 days prior to term). Simultaneous incubation with cycloheximide inhibited the stimulatory effect of these agents on foetal rat liver cystathionase activity in vitro. Dexamethasone and glucagon were both capable of increasing liver cystathionase activity both in newborn and 3-day-old animals in vivo.", "contents": "Induction of cystathionase in foetal rat liver explants. Effects of dexamethasone, N-6, O-2 -dibutyryladenosine 3,5 -monophosphate and glucagon in vitro. At the 18th day of gestation and thereafter foetal rat liver explants in organ culture showed the competence to respond to dexamethasone by increased cystathionase activity, whereas the ability to respond to dibutyryl cyclic AMP or glucagon became evident at a later developmental stage (during the last 2 days prior to term). Simultaneous incubation with cycloheximide inhibited the stimulatory effect of these agents on foetal rat liver cystathionase activity in vitro. Dexamethasone and glucagon were both capable of increasing liver cystathionase activity both in newborn and 3-day-old animals in vivo."} {"id": "PMID:167858", "title": "Reduced glucocorticoid responsiveness and receptor concentration in splenic leukocytes of senescent rats.", "content": "Glucocorticoids are 63% less effective in inhibiting [5-3-h] uridine uptake by splenic leukocytes of senescent rats (24-14 months) than by those of mature adult animals (12-14 months). Scatchard analyses reveal 57% fewer specific glucocorticoid binding sites in cytosols of the senescent group. Reduced binding of cortisol by cytosol macromolecules of intact viable leukocytes at 37 degrees C is also apparent in the older rats. Specific binding of glucocorticoids to cytoplasmic macromolecules appears to be closely linked, if not required, for inhibition of [5-3-hi1 uridine uptake. This is evidenced by the fact that both inhibition and specific binding are simultaneously blocked by progesterone administration. In addition, the amount of specific binding as well as the degree of inhibition of [5-3-h] uridine uptake is concentration dependent up to 2. 10-6 M cortisol. Thus, decreased glucocorticoid reponsiveness in the cells from senescent rats appears to be due primarily to decreased concentrations of specific glucocorticoid receptors.", "contents": "Reduced glucocorticoid responsiveness and receptor concentration in splenic leukocytes of senescent rats. Glucocorticoids are 63% less effective in inhibiting [5-3-h] uridine uptake by splenic leukocytes of senescent rats (24-14 months) than by those of mature adult animals (12-14 months). Scatchard analyses reveal 57% fewer specific glucocorticoid binding sites in cytosols of the senescent group. Reduced binding of cortisol by cytosol macromolecules of intact viable leukocytes at 37 degrees C is also apparent in the older rats. Specific binding of glucocorticoids to cytoplasmic macromolecules appears to be closely linked, if not required, for inhibition of [5-3-hi1 uridine uptake. This is evidenced by the fact that both inhibition and specific binding are simultaneously blocked by progesterone administration. In addition, the amount of specific binding as well as the degree of inhibition of [5-3-h] uridine uptake is concentration dependent up to 2. 10-6 M cortisol. Thus, decreased glucocorticoid reponsiveness in the cells from senescent rats appears to be due primarily to decreased concentrations of specific glucocorticoid receptors."} {"id": "PMID:167859", "title": "Modifying actions of calcium ionophores on insulin release.", "content": "Beta-Cell-rich pancreatic islets were microdissected from noninbred ob/obmice and exposed to the calcium ionophores X-537A and A-23187. X-537A differed from A-23187 in being a potent insulin secretagogue at non-stimulating glucose concentrations. Both ionophores inhibited the stimulation of insulin release obtained after adding 20 mM glucose to the incubation medium. The latter observation is consistent with the idea of a reduced beta-cell function when the Ca-2+ in the functionally important intracellular pool (s) exceeds a certain concentration. The ionophore inhibition of the glucose-stimulated insulin release may at least in part result from decreased formation of cyclic AMP, since X-537A proved to be as effective as L-epinephrine in reducing the islet content of this nucleotide in the presence of a phosphodiesterase inhibitor. The secretagogic action of X-537A at a low glucose concentration persisted when different ions were omitted from the incubation medium and was actually considerably enhanced in the absence of extracellular Ca-2+. The insulin-releasing action of X-537A was neither influenced by 3-O-methyglucose nor by drugs blocking the alpha or beta-adrenergic receptor sites. Exposure of the pancreatic beta-cells to metabolic inhibitors in concentrations which significantly reduced the secretory response to glucose, potentiated stimulation of insulin release by X-537A, suggesting that this effect may in part be accounted for by intracellular dissolution of secretory granules.", "contents": "Modifying actions of calcium ionophores on insulin release. Beta-Cell-rich pancreatic islets were microdissected from noninbred ob/obmice and exposed to the calcium ionophores X-537A and A-23187. X-537A differed from A-23187 in being a potent insulin secretagogue at non-stimulating glucose concentrations. Both ionophores inhibited the stimulation of insulin release obtained after adding 20 mM glucose to the incubation medium. The latter observation is consistent with the idea of a reduced beta-cell function when the Ca-2+ in the functionally important intracellular pool (s) exceeds a certain concentration. The ionophore inhibition of the glucose-stimulated insulin release may at least in part result from decreased formation of cyclic AMP, since X-537A proved to be as effective as L-epinephrine in reducing the islet content of this nucleotide in the presence of a phosphodiesterase inhibitor. The secretagogic action of X-537A at a low glucose concentration persisted when different ions were omitted from the incubation medium and was actually considerably enhanced in the absence of extracellular Ca-2+. The insulin-releasing action of X-537A was neither influenced by 3-O-methyglucose nor by drugs blocking the alpha or beta-adrenergic receptor sites. Exposure of the pancreatic beta-cells to metabolic inhibitors in concentrations which significantly reduced the secretory response to glucose, potentiated stimulation of insulin release by X-537A, suggesting that this effect may in part be accounted for by intracellular dissolution of secretory granules."} {"id": "PMID:167860", "title": "Inhibitory effect of cortisone acetate on the stimulation of rat liver cytosol L-serrine. Pyruvate aminotransferase by dibutyryl adenosine 3,5-monophosphate.", "content": "An injection of cortisone acetate at a dose of 5 mg/100 g body weight concomitant with dibutyryl cyclic AMP prevents the increase in the activity of rat liver cytosol serine aminotransferase (L-serine:pyruvate aminotransferase, EC 2.6.1.51) elicited by the nucleotide with a lag of about 2 h. If the glucocorticoid is given 2 h prior to the nucleotide inducer, the lag disappears. The inhibitory effect of cortisone acetate gradually decays and is no longer detectable 12 h following its administration. Theophylline, insulin and glucose at doses which affect significantly the level of tyrosine aminotransferase, have not effect on the level of serine aminotransferase and on the cortisone inhibition. The inhibitory effect of the glucocorticoid on the dibutyryl cyclic AMP-mediated increase in serin aminotransferase diminishes with the age of animall. Increases in the enzyme activity by a single dose of glucagon can also be inhibited by cortisone acetate and actinomycin D as in the case with dibutyryl cyclic AMP as an inducer. The possibility of the existence of a specific inhibitory factor which is formed in response to cortisone acetate is discussed.", "contents": "Inhibitory effect of cortisone acetate on the stimulation of rat liver cytosol L-serrine. Pyruvate aminotransferase by dibutyryl adenosine 3,5-monophosphate. An injection of cortisone acetate at a dose of 5 mg/100 g body weight concomitant with dibutyryl cyclic AMP prevents the increase in the activity of rat liver cytosol serine aminotransferase (L-serine:pyruvate aminotransferase, EC 2.6.1.51) elicited by the nucleotide with a lag of about 2 h. If the glucocorticoid is given 2 h prior to the nucleotide inducer, the lag disappears. The inhibitory effect of cortisone acetate gradually decays and is no longer detectable 12 h following its administration. Theophylline, insulin and glucose at doses which affect significantly the level of tyrosine aminotransferase, have not effect on the level of serine aminotransferase and on the cortisone inhibition. The inhibitory effect of the glucocorticoid on the dibutyryl cyclic AMP-mediated increase in serin aminotransferase diminishes with the age of animall. Increases in the enzyme activity by a single dose of glucagon can also be inhibited by cortisone acetate and actinomycin D as in the case with dibutyryl cyclic AMP as an inducer. The possibility of the existence of a specific inhibitory factor which is formed in response to cortisone acetate is discussed."} {"id": "PMID:167861", "title": "On the location of the sulfhydryl group in bovine plasma albumin.", "content": "A series of spin labels has been empolyed to explore the environment of the sulfhydryl group in bovine plasma albumin. The spin labels consist of the nitroxide-free radical and a maleimide (or iodoacetamide)-attaching group separated by varying chain lenghths. Both sets of spin labels preferentially bind to the sulfhydryl group under appropriate conditions. From the change in the electron spin resonance spectra of these nitroxides as a function of chain length, we conclude that the sulfhydryl group is located in a crevice approx. 9.5 A in depth.", "contents": "On the location of the sulfhydryl group in bovine plasma albumin. A series of spin labels has been empolyed to explore the environment of the sulfhydryl group in bovine plasma albumin. The spin labels consist of the nitroxide-free radical and a maleimide (or iodoacetamide)-attaching group separated by varying chain lenghths. Both sets of spin labels preferentially bind to the sulfhydryl group under appropriate conditions. From the change in the electron spin resonance spectra of these nitroxides as a function of chain length, we conclude that the sulfhydryl group is located in a crevice approx. 9.5 A in depth."} {"id": "PMID:167862", "title": "The application of collagenase, purified by affintiy chromatography, to the isolation of insoluble elastin from bovine aorta.", "content": "Clostridium histolyticum collagenase (clostridiopeptidase A, EC 3.4.4.16), purified by affinity chromatography, was applied to the isolation of insoluble elastin from bovine aorta. The extremely low level of N-terminal residues (1.6 mol per 10(6) g of protein) present in this preparation indicated the almost complete lack of hydrolytic damage caused by the isolation procedure. The amino acid profile of the aortic elastin was found to be almost identical to that of insoluble elastin prepared from bovine ligamentum nuchae by the same method.", "contents": "The application of collagenase, purified by affintiy chromatography, to the isolation of insoluble elastin from bovine aorta. Clostridium histolyticum collagenase (clostridiopeptidase A, EC 3.4.4.16), purified by affinity chromatography, was applied to the isolation of insoluble elastin from bovine aorta. The extremely low level of N-terminal residues (1.6 mol per 10(6) g of protein) present in this preparation indicated the almost complete lack of hydrolytic damage caused by the isolation procedure. The amino acid profile of the aortic elastin was found to be almost identical to that of insoluble elastin prepared from bovine ligamentum nuchae by the same method."} {"id": "PMID:167863", "title": "Nitrogenase. VIII. M\u00f6ssbauer and EPR spectroscopy. The MoFe protein component from Azotobacter vinelandii OP.", "content": "We have studied the molybdenum-iron protein (MoFe protein, also known as component I) from Azobacter vinelandi using M\u00f6ssbauer spectroscopy and electron paramagnetic resonance on samples enriched with 57Fe. These spectra can be interpreted in terms of two EPR active centers, each of which is reducible by one electron. A total of four different chemical environments of Fe can be discerned. One of them is a cluster of Fe atoms with a net electronic spin of 3/2, one of them is high-spin ferrous iron and the remaining two are iron in a reduced state (probably in clusters). The results are as follows: Chemical analysis yields 11.5 Fe atoms and 12.5 labile sulfur atoms per molybdenum atom; the molecule contains two Mo atoms per 300 000 daltons. The EPR spectrum of the MoFe protein exhibits g values at 4.32, 3.65 and 2.01, associated with the ground state doublet of a S = 3/2 spin system. The spin Hamiltonian H = D(S2/z minus 5/4 + lambda(S2/x minus S2/y)) + gbeta/o S-H fits the experimental data for go = 2.00 and lambda = 0.055. Quantitative analysis of the temperature dependence of the EPR spectrum yields D/k = 7.5 degrees K and 0.91 spins/molybdenum atom, which suggests that the MoFe protein has two EPR active centers. Quantitative evaluation of M\u00f6ssbauer spectra shows that approximately 8 iron atoms give rise to one quadrupole doublet; at lower temperatures magnetic spectra, associated with the groud electronic doublet, are observed; at least two magnetically inequivalent sites can be distinguished. Taken together the data suggest that each EPR center contains 4 iron atoms. The EPR and M\u00f6ssbauer data can only be reconciled if these iron atoms reside in a spin-coupled (S = 3/2) cluster. Under nitrogen fixing conditions the magnetic M\u00f6ssbauer spectra disappeared concurrently with the EPR signal and quadrupole doublets are obserced at all temperatures. The data suggest that each EPR active center is reduced by one electron. The M\u00f6ssbauer investigation reveals three other spectral components characteristic of iron nuclei in an environment of integer or zero electronic spin, i.e. they reside in complexes which are \"EPR-silent\". One of the components (3-4 iron atoms) has M\u00f6ssbauer parameters characteristic of the high-spin ferrous iron as in reduced ruberdoxin. However, measurements in strong fields indicate a diamagnetic environment. Another component, representing 9-11 iron atoms, seems to be diamagnetic also. It is suggested that these atoms are incorporated in spin-coupled clusters.", "contents": "Nitrogenase. VIII. M\u00f6ssbauer and EPR spectroscopy. The MoFe protein component from Azotobacter vinelandii OP. We have studied the molybdenum-iron protein (MoFe protein, also known as component I) from Azobacter vinelandi using M\u00f6ssbauer spectroscopy and electron paramagnetic resonance on samples enriched with 57Fe. These spectra can be interpreted in terms of two EPR active centers, each of which is reducible by one electron. A total of four different chemical environments of Fe can be discerned. One of them is a cluster of Fe atoms with a net electronic spin of 3/2, one of them is high-spin ferrous iron and the remaining two are iron in a reduced state (probably in clusters). The results are as follows: Chemical analysis yields 11.5 Fe atoms and 12.5 labile sulfur atoms per molybdenum atom; the molecule contains two Mo atoms per 300 000 daltons. The EPR spectrum of the MoFe protein exhibits g values at 4.32, 3.65 and 2.01, associated with the ground state doublet of a S = 3/2 spin system. The spin Hamiltonian H = D(S2/z minus 5/4 + lambda(S2/x minus S2/y)) + gbeta/o S-H fits the experimental data for go = 2.00 and lambda = 0.055. Quantitative analysis of the temperature dependence of the EPR spectrum yields D/k = 7.5 degrees K and 0.91 spins/molybdenum atom, which suggests that the MoFe protein has two EPR active centers. Quantitative evaluation of M\u00f6ssbauer spectra shows that approximately 8 iron atoms give rise to one quadrupole doublet; at lower temperatures magnetic spectra, associated with the groud electronic doublet, are observed; at least two magnetically inequivalent sites can be distinguished. Taken together the data suggest that each EPR center contains 4 iron atoms. The EPR and M\u00f6ssbauer data can only be reconciled if these iron atoms reside in a spin-coupled (S = 3/2) cluster. Under nitrogen fixing conditions the magnetic M\u00f6ssbauer spectra disappeared concurrently with the EPR signal and quadrupole doublets are obserced at all temperatures. The data suggest that each EPR active center is reduced by one electron. The M\u00f6ssbauer investigation reveals three other spectral components characteristic of iron nuclei in an environment of integer or zero electronic spin, i.e. they reside in complexes which are \"EPR-silent\". One of the components (3-4 iron atoms) has M\u00f6ssbauer parameters characteristic of the high-spin ferrous iron as in reduced ruberdoxin. However, measurements in strong fields indicate a diamagnetic environment. Another component, representing 9-11 iron atoms, seems to be diamagnetic also. It is suggested that these atoms are incorporated in spin-coupled clusters."} {"id": "PMID:167864", "title": "A critical evaluation of the proposal that serum apolipoproteins are the major constituents of the human erythrocyte membrane.", "content": "1. The EDTA and Triton X-100 extracts of human erythrocyte ghosts gave no precipitin lines in double diffusion analyses with antibodies to either lipoprotein A, lipoprotein B, lipoprotein C, lipoprotein D, Lp(a) lipoprotein or arginine-rich apolipoprotein of normal human serum (for nomenclature for serum lipoprotein families and apolipoptoteins, see Alaupovic, P., Kostner, G., Lee, D. M., McConathy, W.J. and Magnani, HN. (1972) Expo. Annu. Biochem. Med. 31, 145-160 and Alaupovic, P., Lee, D.M. and McConathy, W.J., (1972) Biochim. Biophys. Acta 260, 689-707.) These membrane preparations also reacted negatively with commercially available antisera to alpha- and beta-lipoproteins. 2. The normal serum very low density, low density and high density lipoproteins formed no precipitin lines with antibodies to either intact or EDTA-extracted ghosts. 3. The serum apolipoproteins and their constitutive polypeptides (A-I, A-II, B, C-I, C-II, C-III, D and arginine-rich apolipoprotein) reacted negatively with antibodies to intact or EDTA-extracted ghosts. The EDTA and Triton X-100 extracts of erythrocyte ghosts gave no reaction with monospecific antibodies to serum apolipoproteins and their constitutive polypeptides. 4. Ghosts dissolved 2% sodium dodecyl sulfate gave positive immunoprecipitin lines with antisera to alpha- and beta-lipoproteins. However, the sodium dodecyl sulfate solution in concentrations greater than 0.1% also formed precipitin lines with antisera to the same lipoproteins. 5. These results do not support the suggestion (Langdon, R.G. (1974) Biochim. Biophys. Acta 342, 213-228) that serum apolipoptoteins are integral protein constituents of human erythrocyte ghosts. The immunoprecipitin lines observed in the latter study might have been due to the presence of trace amounts of serum lipoproteins loosely attached to the cellular surfaces or, more probably, resulted from nonspecific interactions between the proteins and the sodium dodecyl sulfate used as the solubilizing agent", "contents": "A critical evaluation of the proposal that serum apolipoproteins are the major constituents of the human erythrocyte membrane. 1. The EDTA and Triton X-100 extracts of human erythrocyte ghosts gave no precipitin lines in double diffusion analyses with antibodies to either lipoprotein A, lipoprotein B, lipoprotein C, lipoprotein D, Lp(a) lipoprotein or arginine-rich apolipoprotein of normal human serum (for nomenclature for serum lipoprotein families and apolipoptoteins, see Alaupovic, P., Kostner, G., Lee, D. M., McConathy, W.J. and Magnani, HN. (1972) Expo. Annu. Biochem. Med. 31, 145-160 and Alaupovic, P., Lee, D.M. and McConathy, W.J., (1972) Biochim. Biophys. Acta 260, 689-707.) These membrane preparations also reacted negatively with commercially available antisera to alpha- and beta-lipoproteins. 2. The normal serum very low density, low density and high density lipoproteins formed no precipitin lines with antibodies to either intact or EDTA-extracted ghosts. 3. The serum apolipoproteins and their constitutive polypeptides (A-I, A-II, B, C-I, C-II, C-III, D and arginine-rich apolipoprotein) reacted negatively with antibodies to intact or EDTA-extracted ghosts. The EDTA and Triton X-100 extracts of erythrocyte ghosts gave no reaction with monospecific antibodies to serum apolipoproteins and their constitutive polypeptides. 4. Ghosts dissolved 2% sodium dodecyl sulfate gave positive immunoprecipitin lines with antisera to alpha- and beta-lipoproteins. However, the sodium dodecyl sulfate solution in concentrations greater than 0.1% also formed precipitin lines with antisera to the same lipoproteins. 5. These results do not support the suggestion (Langdon, R.G. (1974) Biochim. Biophys. Acta 342, 213-228) that serum apolipoptoteins are integral protein constituents of human erythrocyte ghosts. The immunoprecipitin lines observed in the latter study might have been due to the presence of trace amounts of serum lipoproteins loosely attached to the cellular surfaces or, more probably, resulted from nonspecific interactions between the proteins and the sodium dodecyl sulfate used as the solubilizing agent"} {"id": "PMID:167867", "title": "[Photochemical generation of the cation-radical of bacteriochlorophyll b and the anion-radical of bacteriochlorophyll b and bacteriopheophytin b, components of the photosynthesizing bacteria Rhodopseudomonas viridis].", "content": "The mechanism of photochemical redox reaction of bacteriochlorophyll b, bacteriopheophitin b was studied. The oxidation of bacteriochlorophyll b was carried out in ethanole by means of p-benzoquinone. In ESR spectra the singlet line with delta H = 8.4 gs and g = 2.0025 corresponded to cation-radical. The changes within the region of 400-500 nm, 500-600 nm and the band with the maximum at 685 nm corresponded to cation-radical in the absorption spectra. Photoreduction of bacteriochlorophyll b and bacteriopheophitin b was carried out in triet containing phenilhydrosin. Anion-radicals of bacteriochlorophyll b and bacteriopheophitin b observed in the ESR spectra had singlet form with weak and superthin structure and correspondently with delta H = 10 gs, delta H = 12 gs. The spectrophotometric characteristics of the above pigments were obtained.", "contents": "[Photochemical generation of the cation-radical of bacteriochlorophyll b and the anion-radical of bacteriochlorophyll b and bacteriopheophytin b, components of the photosynthesizing bacteria Rhodopseudomonas viridis]. The mechanism of photochemical redox reaction of bacteriochlorophyll b, bacteriopheophitin b was studied. The oxidation of bacteriochlorophyll b was carried out in ethanole by means of p-benzoquinone. In ESR spectra the singlet line with delta H = 8.4 gs and g = 2.0025 corresponded to cation-radical. The changes within the region of 400-500 nm, 500-600 nm and the band with the maximum at 685 nm corresponded to cation-radical in the absorption spectra. Photoreduction of bacteriochlorophyll b and bacteriopheophitin b was carried out in triet containing phenilhydrosin. Anion-radicals of bacteriochlorophyll b and bacteriopheophitin b observed in the ESR spectra had singlet form with weak and superthin structure and correspondently with delta H = 10 gs, delta H = 12 gs. The spectrophotometric characteristics of the above pigments were obtained."} {"id": "PMID:167871", "title": "Presence of the methylester of 5-carboxymethyl uridine in the wobble position of the anticodon of tRNAIII Arg from brewer's yeast.", "content": "The methylester of 5-carboxymethyluridine (mcm5U), its degradation product 5-carboxymethyluridine (cm5U) and the corresponding nucleotide (cm5Up) were isolated from brewer's yeast tRNAIII Arg or from the dodecanucleotide containing the anticodon. Their chromatographic and electrophoretic properties and their UV absorbing spectra were identical to that of the corresponding synthetic compounds. The gas chromatographic behavior and the mass spectrum of mcm5U obtained from tRNAIII Arg and of a synthetic sample were also identical ; the rare occurence of a thermal reciprocal bimolecular methyl-hydrogen transfer in the mass spectrometer ion source was observed. A mild alkaline treatment of tRNAIII Arg leads to the saponification of mcm5U into cm5U (within the tRNA), which can be again esterified in the presence of a yeast homogenate and (methyl-14C) S adenosylmethionine. The radioactivity was found in the mcm5U located in the wobble position of the anticodon of tRNAIII Arg. The presence of this odd nucleotide in that position could possibly restrict the codon-anticodon interaction of tRNAIII Arg.", "contents": "Presence of the methylester of 5-carboxymethyl uridine in the wobble position of the anticodon of tRNAIII Arg from brewer's yeast. The methylester of 5-carboxymethyluridine (mcm5U), its degradation product 5-carboxymethyluridine (cm5U) and the corresponding nucleotide (cm5Up) were isolated from brewer's yeast tRNAIII Arg or from the dodecanucleotide containing the anticodon. Their chromatographic and electrophoretic properties and their UV absorbing spectra were identical to that of the corresponding synthetic compounds. The gas chromatographic behavior and the mass spectrum of mcm5U obtained from tRNAIII Arg and of a synthetic sample were also identical ; the rare occurence of a thermal reciprocal bimolecular methyl-hydrogen transfer in the mass spectrometer ion source was observed. A mild alkaline treatment of tRNAIII Arg leads to the saponification of mcm5U into cm5U (within the tRNA), which can be again esterified in the presence of a yeast homogenate and (methyl-14C) S adenosylmethionine. The radioactivity was found in the mcm5U located in the wobble position of the anticodon of tRNAIII Arg. The presence of this odd nucleotide in that position could possibly restrict the codon-anticodon interaction of tRNAIII Arg."} {"id": "PMID:167868", "title": "[IR-spectroscopic study of cytochrome C-phospholipid lipoprotein and proteolipid model membranes].", "content": "It is shown by the methods of IR-spectroscopy and peptide hydrogen-deuterium exchange that a) considerable changes in the protein spectra occur (beta-conformation in the protein structure appears) during the interaction in water of cytochrome c molecules with lipid membranes containing negatively charged polar groups; b) further significant changes of the protein spectrum occur under the action of 1% OsO4 and heating up to n plus 95 degrees C; c) the conformational state of the pure protein in water; after the treatments of the proteolipid memebranes with 1% OsO4 and heating up to n degrees C no significant changes of protein spectrum occur, that may suggest hydrophobic interactions between the protein and lipids; d) the treatment of both pure cytichrome c and the model membranes with 1% glutaraldehyde, 30, 60% ethanol and acetone solutions in water does not reveal substantial changes in IR-spectra of the protein moiety.", "contents": "[IR-spectroscopic study of cytochrome C-phospholipid lipoprotein and proteolipid model membranes]. It is shown by the methods of IR-spectroscopy and peptide hydrogen-deuterium exchange that a) considerable changes in the protein spectra occur (beta-conformation in the protein structure appears) during the interaction in water of cytochrome c molecules with lipid membranes containing negatively charged polar groups; b) further significant changes of the protein spectrum occur under the action of 1% OsO4 and heating up to n plus 95 degrees C; c) the conformational state of the pure protein in water; after the treatments of the proteolipid memebranes with 1% OsO4 and heating up to n degrees C no significant changes of protein spectrum occur, that may suggest hydrophobic interactions between the protein and lipids; d) the treatment of both pure cytichrome c and the model membranes with 1% glutaraldehyde, 30, 60% ethanol and acetone solutions in water does not reveal substantial changes in IR-spectra of the protein moiety."} {"id": "PMID:167869", "title": "[Reduction paths of reaction centers of photosystem I of photosynthesis].", "content": "The behaviour of ESR signal I in blue-green algae and chloroplasts is considered under various illumination and with various previous treatment. It is shown that the main process determining the kinetics of P700 plus reduction is the reaction with reduced components of the electron transfer chain between the two photosystems. If the accumulation of the products is inhibited by any way, then the reduction rate depends on the reactions with reducing agents in the incubation medium accumulated under irradiation before experiment. These exogenic reducing agents may be removed from the chloroplasts with repeated washings, and from algae-by means of the dark incubation for a long time. The relation of cyclic and noncyclic electron transfer is considered with and without artificial cyclic flow mediator.", "contents": "[Reduction paths of reaction centers of photosystem I of photosynthesis]. The behaviour of ESR signal I in blue-green algae and chloroplasts is considered under various illumination and with various previous treatment. It is shown that the main process determining the kinetics of P700 plus reduction is the reaction with reduced components of the electron transfer chain between the two photosystems. If the accumulation of the products is inhibited by any way, then the reduction rate depends on the reactions with reducing agents in the incubation medium accumulated under irradiation before experiment. These exogenic reducing agents may be removed from the chloroplasts with repeated washings, and from algae-by means of the dark incubation for a long time. The relation of cyclic and noncyclic electron transfer is considered with and without artificial cyclic flow mediator."} {"id": "PMID:167872", "title": "The mechanism of ferrocytochrome C oxidation by a horseradish isoperoxidase.", "content": "The oxidation of ferrocytochrome c catalysed by highly purified horse-radish isoperoxidase P2 was studied kinetically. To take into account the low turnover number of the enzyme and the tendency to autocatalytic oxidation of ferrocytochrome c, experimental conditions were used which prevented us from using the steady-state treatment. According to kinetic results reported by several authors, a kinetic scheme involving a ternary complex between the enzyme and the substrates was postulated and simulated on a hybrid computer. By assuming that the interaction of peroxidase with hydrogen peroxide is much faster than the interaction with ferrocytochrome c, one can verify that this scheme explains the fact that initial velocity does not vary in relation to the hydrogen peroxide concentration and that a sudden change of slope occurs in the kinetic curve for an initial hydrogen peroxide/ferrocytochrome c ratio lower than 0.5.", "contents": "The mechanism of ferrocytochrome C oxidation by a horseradish isoperoxidase. The oxidation of ferrocytochrome c catalysed by highly purified horse-radish isoperoxidase P2 was studied kinetically. To take into account the low turnover number of the enzyme and the tendency to autocatalytic oxidation of ferrocytochrome c, experimental conditions were used which prevented us from using the steady-state treatment. According to kinetic results reported by several authors, a kinetic scheme involving a ternary complex between the enzyme and the substrates was postulated and simulated on a hybrid computer. By assuming that the interaction of peroxidase with hydrogen peroxide is much faster than the interaction with ferrocytochrome c, one can verify that this scheme explains the fact that initial velocity does not vary in relation to the hydrogen peroxide concentration and that a sudden change of slope occurs in the kinetic curve for an initial hydrogen peroxide/ferrocytochrome c ratio lower than 0.5."} {"id": "PMID:167870", "title": "[Oscillator generator in the lower portion of the glycolytic system].", "content": "A mathematical model explaining the mechanism of autooscillation generation in the lower part of the glycolytic system is suggested. The model is based on substrate inhibition of glyceraldehydephosphatedehydrigenase (GAPDH) with glyceraldehydephosphate (GAP). Pyrimidinenucleotides (NADplus and NADH) are shown not to play an important role in the given oscillation mechanism and can not be considered to simplify the model.", "contents": "[Oscillator generator in the lower portion of the glycolytic system]. A mathematical model explaining the mechanism of autooscillation generation in the lower part of the glycolytic system is suggested. The model is based on substrate inhibition of glyceraldehydephosphatedehydrigenase (GAPDH) with glyceraldehydephosphate (GAP). Pyrimidinenucleotides (NADplus and NADH) are shown not to play an important role in the given oscillation mechanism and can not be considered to simplify the model."} {"id": "PMID:167873", "title": "On the control of septation in Escherichia coli.", "content": "Mutants of E. coli defective in cell septation (ftsA to ftsG, conditional thermosensitive mutants isolated by Ricard and Hirota) were studied with respect to their membrane protein composition, murein hydrolase activities and rates of synthesis of murein and phospholipids. Three classes of mutants have been distinguished: 1) those affected in both murein and phospholipid synthesis; 2) those affected in either murein or phospholipid synthesis and 3) those affected in neither of these parameters. Overall murein hydrolase activities, after activation, is of the same order in all the mutants screened. In addition to soluble products of murein splitting, we have found insoluble products that appear to be in dynamic equilibrium with the murein of the sacculus. Endogenous levels of cyclic adenosine 3',5'-monophosphate measured after blocking septation showed no variation. This suggests that the cyclic nucleotide is not involved in the metabolic control of septation.", "contents": "On the control of septation in Escherichia coli. Mutants of E. coli defective in cell septation (ftsA to ftsG, conditional thermosensitive mutants isolated by Ricard and Hirota) were studied with respect to their membrane protein composition, murein hydrolase activities and rates of synthesis of murein and phospholipids. Three classes of mutants have been distinguished: 1) those affected in both murein and phospholipid synthesis; 2) those affected in either murein or phospholipid synthesis and 3) those affected in neither of these parameters. Overall murein hydrolase activities, after activation, is of the same order in all the mutants screened. In addition to soluble products of murein splitting, we have found insoluble products that appear to be in dynamic equilibrium with the murein of the sacculus. Endogenous levels of cyclic adenosine 3',5'-monophosphate measured after blocking septation showed no variation. This suggests that the cyclic nucleotide is not involved in the metabolic control of septation."} {"id": "PMID:167874", "title": "Effects of microtubule inhibitors and cytochalasin B on thyroid metabolism in vitro.", "content": "Mitotic spindle inhibitors (colchicine, vinblastine, vincristine, 020, ethanol) and cytochalasin B inhibit the phagocytosis of colloid by thyroid cells and the secretion of thyroid hormones. This inhibition has been linked to interferences with the microtubular microfilament system of the follicular cell. In order to test the possibility of using such inhibitors to selectively block secretion, the action of suppressing or highly inhibitory concentrations on other metabolic parameters has been studied on dog thyroid slices in vitro: glucose oxidation, lactate formation, iodide binding to protein, cyclic 3'5' AMP accumulation. It is shown that at a concentration of 10 mM colchicine is entirely non specific as it greatly inhibits all facets of metabolism and all the stimulatory effects of cyclic 3'5' AMP and thyrotropin. The other mictrotubule inhibitors, although affecting thyroid metabolism in various ways were more specified. The enhancement by vineblastine of glucose oxidation ald iodine binding to proteins suggests an activation of they thyroid H2O2 generating system. D2O on the other hand selectively inhibits secretion and the binding of iodide to proteins. Cytochalasin B, presumably by inhibiting hexose transport, decreased glycolysis and the uptake of iodide. However this effect cannot account for the complete inhibition of thyroid secretion.", "contents": "Effects of microtubule inhibitors and cytochalasin B on thyroid metabolism in vitro. Mitotic spindle inhibitors (colchicine, vinblastine, vincristine, 020, ethanol) and cytochalasin B inhibit the phagocytosis of colloid by thyroid cells and the secretion of thyroid hormones. This inhibition has been linked to interferences with the microtubular microfilament system of the follicular cell. In order to test the possibility of using such inhibitors to selectively block secretion, the action of suppressing or highly inhibitory concentrations on other metabolic parameters has been studied on dog thyroid slices in vitro: glucose oxidation, lactate formation, iodide binding to protein, cyclic 3'5' AMP accumulation. It is shown that at a concentration of 10 mM colchicine is entirely non specific as it greatly inhibits all facets of metabolism and all the stimulatory effects of cyclic 3'5' AMP and thyrotropin. The other mictrotubule inhibitors, although affecting thyroid metabolism in various ways were more specified. The enhancement by vineblastine of glucose oxidation ald iodine binding to proteins suggests an activation of they thyroid H2O2 generating system. D2O on the other hand selectively inhibits secretion and the binding of iodide to proteins. Cytochalasin B, presumably by inhibiting hexose transport, decreased glycolysis and the uptake of iodide. However this effect cannot account for the complete inhibition of thyroid secretion."} {"id": "PMID:167875", "title": "[The effect of SH group inhibitors on phosphate transport in Chlorella pyrenoidosa].", "content": "The effect of Sulphydryl reagents have been investigated. pCMB inhibits the transport of phosphate in Chlorella pyrenoidosa. This inhibition is immediate and does not change as a function of time of incubation. This inhibition affects non starved and starved cells (phosphate omitted). pCMPS and Mersalyl act in the same manner as pCMB. When these compounds are used at low concentrations, inhibition of phosphate uptake is observed only in starved cells. The substrate (phosphate) cannot provide protection against this inhibition. NEM inhibits phosphate uptake and this inhibition increases as a function of time of incubation. When the time of incubation is very short (about 15 seconds) the effects seems to be superficial and NEM reacts with SH groups involved in the transport system. When phosphate is present (for 15 seconds of incubation with NEM) the inhibition is less important than when phosphate is omitted. The substrate protects against NEM, but this protection disappears as the incubation with NEM is prolonged. NEM inhibits phosphate uptake in non starved and starved cells, however, it is observed that the inhibition is less important in starved cells than in non starved cells. The authors conclude that two kinds of SH groups might exist in the phosphate transport system, one reacting with pCMB and the other with NEM.", "contents": "[The effect of SH group inhibitors on phosphate transport in Chlorella pyrenoidosa]. The effect of Sulphydryl reagents have been investigated. pCMB inhibits the transport of phosphate in Chlorella pyrenoidosa. This inhibition is immediate and does not change as a function of time of incubation. This inhibition affects non starved and starved cells (phosphate omitted). pCMPS and Mersalyl act in the same manner as pCMB. When these compounds are used at low concentrations, inhibition of phosphate uptake is observed only in starved cells. The substrate (phosphate) cannot provide protection against this inhibition. NEM inhibits phosphate uptake and this inhibition increases as a function of time of incubation. When the time of incubation is very short (about 15 seconds) the effects seems to be superficial and NEM reacts with SH groups involved in the transport system. When phosphate is present (for 15 seconds of incubation with NEM) the inhibition is less important than when phosphate is omitted. The substrate protects against NEM, but this protection disappears as the incubation with NEM is prolonged. NEM inhibits phosphate uptake in non starved and starved cells, however, it is observed that the inhibition is less important in starved cells than in non starved cells. The authors conclude that two kinds of SH groups might exist in the phosphate transport system, one reacting with pCMB and the other with NEM."} {"id": "PMID:167876", "title": "[Applications of electron paramagnetic resonance to the study of biological molecules].", "content": "In a first part, an elementary theoretical introduction to ESR is given. In a second part, selected examples illustrate the possibilities of this method. Studies of hemoproteins, flavoproteins, model complexes and phospholipid systems are described. This review is made for biochemists who have no experience in ESR.", "contents": "[Applications of electron paramagnetic resonance to the study of biological molecules]. In a first part, an elementary theoretical introduction to ESR is given. In a second part, selected examples illustrate the possibilities of this method. Studies of hemoproteins, flavoproteins, model complexes and phospholipid systems are described. This review is made for biochemists who have no experience in ESR."} {"id": "PMID:167877", "title": "Electron spin resonance study of melanin treated with reducing agents.", "content": "The electron spin resonances (ESR) of several native and modified melanins have been determined. Melanins isolated from black wool and synthesized from 3,4-dihydroxyl-L-phenylalanine (L-DOPA) and tyrosine all show similar ESR signals. Modification of the isolated melanins by treatment with reducing agents causes some lightening in color and slight changes in the ESR spectra. Lithium and liquid ammonia (Birch) reduction applied to melanins from wool and L-DOPA gave very different results, as reflected by ESR spectra, but in both cases the changes were much greater than those produced by other treatments. In general, reductive treatments in nonaqueous media in the presence of metals increase the free radical content and line width, whereas treatment in aqueous media resulted in decreased free radical content. These observations are consistent with a melanin pigment which is an irregular polymer and has unpaired electrons localized on different but similar monomer units.", "contents": "Electron spin resonance study of melanin treated with reducing agents. The electron spin resonances (ESR) of several native and modified melanins have been determined. Melanins isolated from black wool and synthesized from 3,4-dihydroxyl-L-phenylalanine (L-DOPA) and tyrosine all show similar ESR signals. Modification of the isolated melanins by treatment with reducing agents causes some lightening in color and slight changes in the ESR spectra. Lithium and liquid ammonia (Birch) reduction applied to melanins from wool and L-DOPA gave very different results, as reflected by ESR spectra, but in both cases the changes were much greater than those produced by other treatments. In general, reductive treatments in nonaqueous media in the presence of metals increase the free radical content and line width, whereas treatment in aqueous media resulted in decreased free radical content. These observations are consistent with a melanin pigment which is an irregular polymer and has unpaired electrons localized on different but similar monomer units."} {"id": "PMID:167878", "title": "Iontophoresis of cyclic AMP.", "content": "The design, calibration, and operation of a source of controlled amounts of cyclic AMP (c-AMP) are described. Typically, 1.5 s pulses containing 10(10)-10(-12) molecules of c-AMP can be delivered to a region about 10 mum in diameter on an agar plate. The resulting concentration profiles are given as functions of distance and time. The diffusion coefficient of c-AMP in agar was measured to be 0.97 times 10(-5) cm2-s-1 at 21 degrees C.", "contents": "Iontophoresis of cyclic AMP. The design, calibration, and operation of a source of controlled amounts of cyclic AMP (c-AMP) are described. Typically, 1.5 s pulses containing 10(10)-10(-12) molecules of c-AMP can be delivered to a region about 10 mum in diameter on an agar plate. The resulting concentration profiles are given as functions of distance and time. The diffusion coefficient of c-AMP in agar was measured to be 0.97 times 10(-5) cm2-s-1 at 21 degrees C."} {"id": "PMID:167879", "title": "Stimulation of late interphase Dictyostelium discoideum amoebae with an external cyclic AMP signal.", "content": "The microelectrode system described in the accompanying paper was used to investigate properties of fields of Dictyostelium discoideum amoebae in late interphase. Cells in the fields were competent to respond chemotactically to, and to relay, a c-AMP signal, but not to produce an aggregative signal autonomously. The experimental results are generally consistent with c-AMP being the sole compound required for chemotaxis and signal relaying. A periodic signal from the microelectrode can initiate and control aggregation and can complete with spontaneously arising aggregates. The electrode was used to measure the refractory period for relaying which decreases from 9 min or more to between 2 and 3 min with increasing developmental age, and to measure thresholds for chemotaxis and signal relaying. The results are discussed in relation to models for the control of aggregation in D. discoideum.", "contents": "Stimulation of late interphase Dictyostelium discoideum amoebae with an external cyclic AMP signal. The microelectrode system described in the accompanying paper was used to investigate properties of fields of Dictyostelium discoideum amoebae in late interphase. Cells in the fields were competent to respond chemotactically to, and to relay, a c-AMP signal, but not to produce an aggregative signal autonomously. The experimental results are generally consistent with c-AMP being the sole compound required for chemotaxis and signal relaying. A periodic signal from the microelectrode can initiate and control aggregation and can complete with spontaneously arising aggregates. The electrode was used to measure the refractory period for relaying which decreases from 9 min or more to between 2 and 3 min with increasing developmental age, and to measure thresholds for chemotaxis and signal relaying. The results are discussed in relation to models for the control of aggregation in D. discoideum."} {"id": "PMID:167880", "title": "The effects of protein deprivation on cell-mediated immunity.", "content": "The effect of protein insufficiency on immune responsiveness was investigated in inbred mice fed isocaloric diets low and normal in protein. Mice were tested for aberrations of cell-mediated and humoral immunities. Protein insufficiency enhances cell-mediated immunity while depressing or not affecting humoral immunity. Cell-mediated immunity was enhanced in testing: allogeneic skin graft rejection, spleen cell responsiveness to phytohemagglutinin, the graft-vs-host reaction, macrophage function, and resistance to viral and bacterial infections.", "contents": "The effects of protein deprivation on cell-mediated immunity. The effect of protein insufficiency on immune responsiveness was investigated in inbred mice fed isocaloric diets low and normal in protein. Mice were tested for aberrations of cell-mediated and humoral immunities. Protein insufficiency enhances cell-mediated immunity while depressing or not affecting humoral immunity. Cell-mediated immunity was enhanced in testing: allogeneic skin graft rejection, spleen cell responsiveness to phytohemagglutinin, the graft-vs-host reaction, macrophage function, and resistance to viral and bacterial infections."} {"id": "PMID:167881", "title": "Immune deficiency in congenital rubella and other viral infections.", "content": "No immunologic explanation has been found for the chronicity commonly observed in congenital viral infections. In the presence of a humoral immune response, there is continued viral excretion--in rubella for many months, and in the herpes viruses perhaps for life. Infection with rubella early in utero has a profound effect on the developing immune system. Defects observed are: complete immune paralysis, PHA unresponsiveness, immunoglobulin abnormalities, and loss of antibody to rubella. These defects are transient; absence of IgA may be permanent. No such defects have been observed in other congenital viral infections, but precocious development of immune globulin levels and germinal follicles occurs.", "contents": "Immune deficiency in congenital rubella and other viral infections. No immunologic explanation has been found for the chronicity commonly observed in congenital viral infections. In the presence of a humoral immune response, there is continued viral excretion--in rubella for many months, and in the herpes viruses perhaps for life. Infection with rubella early in utero has a profound effect on the developing immune system. Defects observed are: complete immune paralysis, PHA unresponsiveness, immunoglobulin abnormalities, and loss of antibody to rubella. These defects are transient; absence of IgA may be permanent. No such defects have been observed in other congenital viral infections, but precocious development of immune globulin levels and germinal follicles occurs."} {"id": "PMID:167885", "title": "The pituitary dwarf mouse: a model for study of endocrine immunodeficiency disease.", "content": "Pituitary dwarf mutants of the Snell-Bagg and Ames mouse strains develop severe immunodeficiency of the thymus-dependent system which frequently leads to a fatal wasting syndrome. This immunodeficiency is a consequence of defective pituitary influences which will cause 1) an inadequate production of immunocompetent cells due to a central developmental defect primarily affecting the thymus and 2) the inability of immunocompetent cells to undergo a rapid and efficient antigen-induced proliferation and differentiation into antibody-forming cells. The relevance of the dwarf mouse model to a possible association between human immunodeficiency and endocrine disease is briefly discussed.", "contents": "The pituitary dwarf mouse: a model for study of endocrine immunodeficiency disease. Pituitary dwarf mutants of the Snell-Bagg and Ames mouse strains develop severe immunodeficiency of the thymus-dependent system which frequently leads to a fatal wasting syndrome. This immunodeficiency is a consequence of defective pituitary influences which will cause 1) an inadequate production of immunocompetent cells due to a central developmental defect primarily affecting the thymus and 2) the inability of immunocompetent cells to undergo a rapid and efficient antigen-induced proliferation and differentiation into antibody-forming cells. The relevance of the dwarf mouse model to a possible association between human immunodeficiency and endocrine disease is briefly discussed."} {"id": "PMID:167888", "title": "The effects of ATP on platelets: evidence against the central role of released ADP in primary aggregation.", "content": "The influence of freshly purified ATP on the effects of aggregating agents on human platelets was studied. ATP inhibited aggregation induced by ADP competitively (Ki = 20 muM) and immediately without need for prior incubation. ATP had no effect on primary aggregation induced by adrenaline, thrombin, vasopressin, or 5-hydroxytryptamine (5HT). ATP inhibited the shape change and the consumption of metabolic ATP induced by ADP but did not inhibit these effects when induced by thrombin, vasopressin, or 5HT. ATP counteracted the inhibition by ADP of PGE1-stimulated cyclic AMP production in platelets but did not reduce inhibition by adrenaline. It is concluded that adrenaline, thrombin, 5HT, and vasopressin each can induce primary aggregation of human platelets by a mechanism independent of extracellular ADP.", "contents": "The effects of ATP on platelets: evidence against the central role of released ADP in primary aggregation. The influence of freshly purified ATP on the effects of aggregating agents on human platelets was studied. ATP inhibited aggregation induced by ADP competitively (Ki = 20 muM) and immediately without need for prior incubation. ATP had no effect on primary aggregation induced by adrenaline, thrombin, vasopressin, or 5-hydroxytryptamine (5HT). ATP inhibited the shape change and the consumption of metabolic ATP induced by ADP but did not inhibit these effects when induced by thrombin, vasopressin, or 5HT. ATP counteracted the inhibition by ADP of PGE1-stimulated cyclic AMP production in platelets but did not reduce inhibition by adrenaline. It is concluded that adrenaline, thrombin, 5HT, and vasopressin each can induce primary aggregation of human platelets by a mechanism independent of extracellular ADP."} {"id": "PMID:167889", "title": "A survey of intestinal parasitism in a community on the Pan American Highway route in eastern Panama.", "content": "A survey of intestinal parasitism was conducted at Yaviza, a town in eastern Panama's Province of Darien. Single stool specimens from 202 persons, representing 11 percent of the town's total population, were examined. In all, 181 (90 per cent) of the specimens examined were found positive for one or more potentially pathogenic parasites. The most common parasite found was Trichuris trichiura, which was observed in 80 per cent of the samples. Others were Ascaris lumbricoides, in 62 per cent of the samples; hookworm, in 41 per cent; Entamoeba histolytica, in 16 per cent; Stronhyloides stercoralis, in 7 per cent; Giardia lamblia, in 5 per cent; and Hymenolepis diminuta, in 0.5 per cent. The aim of the survey was to gather baseline data on parasite prevalence before the Pan American Highway passes through this area. Construction of the highway is producing marked environmental change. in eastern Panama, and it is anticipated that the date from the survey will prove useful in later efforts to assess the health impact of that change.", "contents": "A survey of intestinal parasitism in a community on the Pan American Highway route in eastern Panama. A survey of intestinal parasitism was conducted at Yaviza, a town in eastern Panama's Province of Darien. Single stool specimens from 202 persons, representing 11 percent of the town's total population, were examined. In all, 181 (90 per cent) of the specimens examined were found positive for one or more potentially pathogenic parasites. The most common parasite found was Trichuris trichiura, which was observed in 80 per cent of the samples. Others were Ascaris lumbricoides, in 62 per cent of the samples; hookworm, in 41 per cent; Entamoeba histolytica, in 16 per cent; Stronhyloides stercoralis, in 7 per cent; Giardia lamblia, in 5 per cent; and Hymenolepis diminuta, in 0.5 per cent. The aim of the survey was to gather baseline data on parasite prevalence before the Pan American Highway passes through this area. Construction of the highway is producing marked environmental change. in eastern Panama, and it is anticipated that the date from the survey will prove useful in later efforts to assess the health impact of that change."} {"id": "PMID:167892", "title": "Investigation of the vasodilator and antisecretory role of prostaglandins in the rat gastric mucosa by use of non-steroidal anti-inflammatory drugs.", "content": "1 The effects of non-steroidal anti-inflammatory drugs on gastric acid secretion and mucosal blood flow were studied in the rat. 2 Indomethacin, in ulcerogenic doses, caused a dose-dependent rise in pentagastrin-stimulated acid secretion, but decreased mucosal blood flow per unit acid secretion. 3 During resting conditions, indomethacin had no significant effect on acid output, but reduced mucosal blood flow. 4 Pretreatment with indomethacin, phenylbutazone or meclofenamate potentiated the secretory response to dibutyryl cyclic adenosine 3',5'-monophosphate. 5 Indomethacin markedly reduced the mucosal prostaglandin-like activity at a time when mucosal erosion formation had reached steady levels. 6 These results provide evidence that prostaglandins have a local role in the regulation of blood flow and acid secretion in the rat gastric mucosa, and suggest that non-steroidal anti-inflammatory drugs cause mucosal erosions by disrupting these processes.", "contents": "Investigation of the vasodilator and antisecretory role of prostaglandins in the rat gastric mucosa by use of non-steroidal anti-inflammatory drugs. 1 The effects of non-steroidal anti-inflammatory drugs on gastric acid secretion and mucosal blood flow were studied in the rat. 2 Indomethacin, in ulcerogenic doses, caused a dose-dependent rise in pentagastrin-stimulated acid secretion, but decreased mucosal blood flow per unit acid secretion. 3 During resting conditions, indomethacin had no significant effect on acid output, but reduced mucosal blood flow. 4 Pretreatment with indomethacin, phenylbutazone or meclofenamate potentiated the secretory response to dibutyryl cyclic adenosine 3',5'-monophosphate. 5 Indomethacin markedly reduced the mucosal prostaglandin-like activity at a time when mucosal erosion formation had reached steady levels. 6 These results provide evidence that prostaglandins have a local role in the regulation of blood flow and acid secretion in the rat gastric mucosa, and suggest that non-steroidal anti-inflammatory drugs cause mucosal erosions by disrupting these processes."} {"id": "PMID:167893", "title": "The effect of reserpine on hypothalamo-pituitary-adrenocortical function in the rat.", "content": "1. The effect of reserpine on hypothalamo-pituitary-adrenocortical (HPA) function in the rat was investigated by the use of direct and indirect indices of pituitary adrenocorticotrophic activity. 2. Administration of a single dose of the drug induced prolonged hypersecretion of corticotrophin (ACTH). 3. Corticotrophin release in response to the drug no longer occurred after repeated daily injections, indicating that some form of 'adaptation' occurred. 4. The increase in HPA activity normally caused by exposure to cold was prevented by reserpine once 'adaptation' to the drug had been produced. 5. Inhibition of stress-induced ACTH release was due neither to depletion of pituitary stores of the hormone, nor to a corticosteroid feedback effect.", "contents": "The effect of reserpine on hypothalamo-pituitary-adrenocortical function in the rat. 1. The effect of reserpine on hypothalamo-pituitary-adrenocortical (HPA) function in the rat was investigated by the use of direct and indirect indices of pituitary adrenocorticotrophic activity. 2. Administration of a single dose of the drug induced prolonged hypersecretion of corticotrophin (ACTH). 3. Corticotrophin release in response to the drug no longer occurred after repeated daily injections, indicating that some form of 'adaptation' occurred. 4. The increase in HPA activity normally caused by exposure to cold was prevented by reserpine once 'adaptation' to the drug had been produced. 5. Inhibition of stress-induced ACTH release was due neither to depletion of pituitary stores of the hormone, nor to a corticosteroid feedback effect."} {"id": "PMID:167894", "title": "The effects of adenosine triphosphate and adenosine diphosphate on transmission at the rat and frog neuromuscular junctions.", "content": "1 The effects of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were investigated on evoked end-plate potentials (e.p.ps) and on miniature end-plate potentials (min. e.p.ps) recorded from muscle fibres of the rat diaphragm and the frog sartorius.2 ATP and ADP decreased the quantum content of the e.p.ps and the frequency of the min. e.p.ps. The maximum effects produced by the two substances were similar.3 The potency of ATP was found to be similar to that of adenosine. In the presence of adenosine, in a concentration producing its maximum effect, the addition of ATP had no further effect. This is compatible with the idea that ATP acts in the same way as adenosine.", "contents": "The effects of adenosine triphosphate and adenosine diphosphate on transmission at the rat and frog neuromuscular junctions. 1 The effects of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were investigated on evoked end-plate potentials (e.p.ps) and on miniature end-plate potentials (min. e.p.ps) recorded from muscle fibres of the rat diaphragm and the frog sartorius.2 ATP and ADP decreased the quantum content of the e.p.ps and the frequency of the min. e.p.ps. The maximum effects produced by the two substances were similar.3 The potency of ATP was found to be similar to that of adenosine. In the presence of adenosine, in a concentration producing its maximum effect, the addition of ATP had no further effect. This is compatible with the idea that ATP acts in the same way as adenosine."} {"id": "PMID:167899", "title": "Hepatic resection.", "content": "One hundred and twenty-five hepatic resections were done in the University Surgical Unit at the Queen Mary Hospital, Hong Kong, from 1964 to 1974 for conditions varying from primary hepatoma and recurrent pyogenic cholangitis to spontaneous rupture of the liver due to a bleeding haemangioma. The overall mortality was 17.6 per cent. A case was classed as an operative death unless the patient was discharged from hospital. There has been long term survival after resection for primary carcinoma of the liver and no mortality when resection was carried out for benign conditions.", "contents": "Hepatic resection. One hundred and twenty-five hepatic resections were done in the University Surgical Unit at the Queen Mary Hospital, Hong Kong, from 1964 to 1974 for conditions varying from primary hepatoma and recurrent pyogenic cholangitis to spontaneous rupture of the liver due to a bleeding haemangioma. The overall mortality was 17.6 per cent. A case was classed as an operative death unless the patient was discharged from hospital. There has been long term survival after resection for primary carcinoma of the liver and no mortality when resection was carried out for benign conditions."} {"id": "PMID:167900", "title": "Effect of surgical trauma on plasma concentrations of cyclic AMP and cortisol.", "content": "The response of plasma cortisol and cyclic AMP concentrations to surgical trauma was examined in 7 general surgical patients. Five patients made uncomplicated recoveries and showed peak cortisol levels at 6 hours postoperatively, returning to normal by 24 hours. On patient developed postoperative pneumonia and the plasma cortisol remained elevated up to 48 hours, and the final patient showed no cortisol response at all. The plasma cyclic AMP concentrations showed a consistent rise during the operation itself, which was statistically significant when compared with preoperative levels (P less than 0.0125). Concentrations had fallen to normal by 6 hours in all the cases, except in the patient who developed pneumonia, where the plasma cyclic AMP also showed a prolonged elevation. The significance of these findings requires further elucidation, but the temporal relationship of the cyclic AMP and cortisol peaks would support the hypothesis that cyclic AMP may play a part in the mediation of ACTH release following surgical trauma.", "contents": "Effect of surgical trauma on plasma concentrations of cyclic AMP and cortisol. The response of plasma cortisol and cyclic AMP concentrations to surgical trauma was examined in 7 general surgical patients. Five patients made uncomplicated recoveries and showed peak cortisol levels at 6 hours postoperatively, returning to normal by 24 hours. On patient developed postoperative pneumonia and the plasma cortisol remained elevated up to 48 hours, and the final patient showed no cortisol response at all. The plasma cyclic AMP concentrations showed a consistent rise during the operation itself, which was statistically significant when compared with preoperative levels (P less than 0.0125). Concentrations had fallen to normal by 6 hours in all the cases, except in the patient who developed pneumonia, where the plasma cyclic AMP also showed a prolonged elevation. The significance of these findings requires further elucidation, but the temporal relationship of the cyclic AMP and cortisol peaks would support the hypothesis that cyclic AMP may play a part in the mediation of ACTH release following surgical trauma."} {"id": "PMID:167903", "title": "Plasma corticotrophin levels in addison-schilder's disease.", "content": "Raised plasma immunoreactive corticotrophin (ACTH) levels were found in five boys with the sex-linked disorder progressive leucodystrophy associated with adrenal insufficiency (Addison-Schilder's disease) and in a symptom-free brother of one of them. Similar ACTH concentrations were found using two antisera, one against the N-terminal part of the ACTH molecule and the other against the C-terminal part. In one patient the circulating ACTH had normal biological activity as measured using the cytochemical ACTH bioassay. Immunoreactive beta/-melanocyte-stimulating hormone was also determined in one patient and found to be raised.", "contents": "Plasma corticotrophin levels in addison-schilder's disease. Raised plasma immunoreactive corticotrophin (ACTH) levels were found in five boys with the sex-linked disorder progressive leucodystrophy associated with adrenal insufficiency (Addison-Schilder's disease) and in a symptom-free brother of one of them. Similar ACTH concentrations were found using two antisera, one against the N-terminal part of the ACTH molecule and the other against the C-terminal part. In one patient the circulating ACTH had normal biological activity as measured using the cytochemical ACTH bioassay. Immunoreactive beta/-melanocyte-stimulating hormone was also determined in one patient and found to be raised."} {"id": "PMID:167905", "title": "Biochemical studies on myelin isolated from the brains of patients with Down's syndrome.", "content": "Amyelination has been deduced from the data on chemical studies of myelin isolated from the brains of Down's syndrome. The lack of cholesterol and much reduced phosphohydrolase activity in mongol myelin possibly suggest a fault in the structure of myelin.", "contents": "Biochemical studies on myelin isolated from the brains of patients with Down's syndrome. Amyelination has been deduced from the data on chemical studies of myelin isolated from the brains of Down's syndrome. The lack of cholesterol and much reduced phosphohydrolase activity in mongol myelin possibly suggest a fault in the structure of myelin."} {"id": "PMID:167906", "title": "Raphe origin of serotonergic nerves terminating in the cerebral ventricles.", "content": "The dorsal and median raphe nuclei of the midbrain are known to contain the perikarya of origin of the major serotonergic (indoleamine) neurons projecting to the parenchyma of the forebrain. Lesions were placed in these nuclei to determine whether serotonin-containing nerve terminals in the cerebral ventricular system are also derived from the raphe nuclei. Brain tissue from control rats and rats 2-7 days after placement of raphe lesions was examined by fluorescence and electron microscopy. By the third day after lesion there was a marked reduction in the formaldehyde-induced fluorescence of supra-ependymal terminals. By the same time virtually all supra-ependymal terminals showed advanced degenerative changes as visualized by electron microscopy. There was a degeneration of supra-ependymal terminals in all parts of the cerebral ventricular system examined, including the epithalamic region (e.g., habenula and pineal recess; serotonin-containing terminals in the latter areas had previously been thought to arise from modified pinealocytes in the pineal recess). We conclude that most, if not all, supra-ependymal nerve terminals are derived from serotonergic cells of origin in the raphe nuclei.", "contents": "Raphe origin of serotonergic nerves terminating in the cerebral ventricles. The dorsal and median raphe nuclei of the midbrain are known to contain the perikarya of origin of the major serotonergic (indoleamine) neurons projecting to the parenchyma of the forebrain. Lesions were placed in these nuclei to determine whether serotonin-containing nerve terminals in the cerebral ventricular system are also derived from the raphe nuclei. Brain tissue from control rats and rats 2-7 days after placement of raphe lesions was examined by fluorescence and electron microscopy. By the third day after lesion there was a marked reduction in the formaldehyde-induced fluorescence of supra-ependymal terminals. By the same time virtually all supra-ependymal terminals showed advanced degenerative changes as visualized by electron microscopy. There was a degeneration of supra-ependymal terminals in all parts of the cerebral ventricular system examined, including the epithalamic region (e.g., habenula and pineal recess; serotonin-containing terminals in the latter areas had previously been thought to arise from modified pinealocytes in the pineal recess). We conclude that most, if not all, supra-ependymal nerve terminals are derived from serotonergic cells of origin in the raphe nuclei."} {"id": "PMID:167909", "title": "Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hippocampal slice.", "content": "Field potentials evoked by stimulation of afferent fibers in stratum radiatum were recorded in the CA1 region of the hippocampal slice maintained in vitro. Stimulation rates of 3-50/sec produced a large increase in amplitude of the population spike in CA1. This increase was maintained for several hours after the tetanization. The facilitation phenomenon appeared to be specific to the synapse of stratum radiatum afferents onto CA1 pyramidal cells since: (1) stimulation outside the radiatum layer did not produce the effect, (2) antidromic field potentials recorded in CA3 were unchanged, (3) EPSP threshold in CA1 was unchanged, and (4) alveus tetanization did not produce a facilitatory effect.", "contents": "Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hippocampal slice. Field potentials evoked by stimulation of afferent fibers in stratum radiatum were recorded in the CA1 region of the hippocampal slice maintained in vitro. Stimulation rates of 3-50/sec produced a large increase in amplitude of the population spike in CA1. This increase was maintained for several hours after the tetanization. The facilitation phenomenon appeared to be specific to the synapse of stratum radiatum afferents onto CA1 pyramidal cells since: (1) stimulation outside the radiatum layer did not produce the effect, (2) antidromic field potentials recorded in CA3 were unchanged, (3) EPSP threshold in CA1 was unchanged, and (4) alveus tetanization did not produce a facilitatory effect."} {"id": "PMID:167911", "title": "Subcellular analysis of the accumulation of estrogen by the brain of male and female rats.", "content": "Three experiments were preformed to provide additional information on the interaction of estrogen with subcellular components of the brain of male and female rats. In experiment 1 tritiated estradiol was administered to adult gonadectomized male and female rats which were then sacrificed 15,60 or 120 min later. Hypothalamic, cortical and pituitary samples were taken and were separated into nuclear and cytosol fractions. For the hypothalamic tissue from females nuclear concentration of radioactivity increased throughout the 2 h period while for males nuclear concentration rose during the first h and then declined. There was a significant sex difference in hypothalamic nuclear concentration of estrogen, male levels being lower. For both sexes cytosol levels progressively declined. For cortical tissue, nuclear radioactivity levels were low and relatively constant for both sexes, while cytosol levels fell during the 2 h period. Pituitary tissue showed a pattern in both nuclear and cytosol fractions which resembled the hypothalamic pattern although absolute levels were higher in the nuclear fraction. In experiment 2 male and female rats were administered labeled and unlabeled estradiol concurrently and were sacrificed 60 and 120 min later. Radioactivity levels were reduced in hypothalamic and pituitarynuclei, but not in cortical nuclei in comparison with animals not administered unlabeled hormone. In experiment 3 males and females were administered tritiated estradiol and were sacrificed 2 h later. The brain of each animal was split longitudinally. One half of each hypothalamic and cortical sample was subjected to nuclear separation while the other half was digested in tissue solubilizer before radioactivity counting. The former procedure showed a substantially greater nuclear concentration of radioactivity for hypothalamic tissue from females than from males. The whole tissue analysis showed only a slight sex difference for hypothalamic tissue. Sex differences were small by either procedure for cortical tissue. It was concluded that the hypothalamus of both male and female rats contains a limited capacit nuclear binding system for estrogen, but that the system is quantitatively less effective in binding estrogen in males.", "contents": "Subcellular analysis of the accumulation of estrogen by the brain of male and female rats. Three experiments were preformed to provide additional information on the interaction of estrogen with subcellular components of the brain of male and female rats. In experiment 1 tritiated estradiol was administered to adult gonadectomized male and female rats which were then sacrificed 15,60 or 120 min later. Hypothalamic, cortical and pituitary samples were taken and were separated into nuclear and cytosol fractions. For the hypothalamic tissue from females nuclear concentration of radioactivity increased throughout the 2 h period while for males nuclear concentration rose during the first h and then declined. There was a significant sex difference in hypothalamic nuclear concentration of estrogen, male levels being lower. For both sexes cytosol levels progressively declined. For cortical tissue, nuclear radioactivity levels were low and relatively constant for both sexes, while cytosol levels fell during the 2 h period. Pituitary tissue showed a pattern in both nuclear and cytosol fractions which resembled the hypothalamic pattern although absolute levels were higher in the nuclear fraction. In experiment 2 male and female rats were administered labeled and unlabeled estradiol concurrently and were sacrificed 60 and 120 min later. Radioactivity levels were reduced in hypothalamic and pituitarynuclei, but not in cortical nuclei in comparison with animals not administered unlabeled hormone. In experiment 3 males and females were administered tritiated estradiol and were sacrificed 2 h later. The brain of each animal was split longitudinally. One half of each hypothalamic and cortical sample was subjected to nuclear separation while the other half was digested in tissue solubilizer before radioactivity counting. The former procedure showed a substantially greater nuclear concentration of radioactivity for hypothalamic tissue from females than from males. The whole tissue analysis showed only a slight sex difference for hypothalamic tissue. Sex differences were small by either procedure for cortical tissue. It was concluded that the hypothalamus of both male and female rats contains a limited capacit nuclear binding system for estrogen, but that the system is quantitatively less effective in binding estrogen in males."} {"id": "PMID:167913", "title": "Physiological and pharmacological evidence for a serotonergic projection to the hippocampus.", "content": "Rat hippocampal pyramidal cells were studied for their response to serotonin applied iontophoretically and to stimulation of the midbrain raphe nuclei. Ninety-two percent of the cells studied were inhibited by serotonin. Fourty-eight percent of the cells responded by inhibition to dorsal and median raphe stimulation. The inhibitory response to raphe stimulation was absent when the rats were pretreated with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor; PCPA effects were alleviated by 5-HTP or 5-HT administration. The response to raphe stimulation was blocked by emthysergide and cyproheptadine. The responses to raphe stimulation were potentiated by chlorimipramine, a serotonin reuptake blocker. These data satisfy several of the criteria required to identify serotonin as the inhibitory neurotransmitter for the raphe-hippocampal pathway", "contents": "Physiological and pharmacological evidence for a serotonergic projection to the hippocampus. Rat hippocampal pyramidal cells were studied for their response to serotonin applied iontophoretically and to stimulation of the midbrain raphe nuclei. Ninety-two percent of the cells studied were inhibited by serotonin. Fourty-eight percent of the cells responded by inhibition to dorsal and median raphe stimulation. The inhibitory response to raphe stimulation was absent when the rats were pretreated with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor; PCPA effects were alleviated by 5-HTP or 5-HT administration. The response to raphe stimulation was blocked by emthysergide and cyproheptadine. The responses to raphe stimulation were potentiated by chlorimipramine, a serotonin reuptake blocker. These data satisfy several of the criteria required to identify serotonin as the inhibitory neurotransmitter for the raphe-hippocampal pathway"} {"id": "PMID:167914", "title": "Denervation in the primary olfactory pathway of mice. II. Effects on carnosine and other amine compounds.", "content": "Carnosine (beta-alanyl-histidine) is present in the olfactory bulb and olfactory eqithelium of mice and rats at 1-2 nmole/mg tissue. Peripheral deafferentation or central denervation causes a rapid, selective decrease of this depeptide from the reciprocal portion of the primary olfactory pathway. These data demonstrate the localization of carnosine within the primary olfactory chemoreceptor neurons and suggest a possible role for this compound in neural transmission.", "contents": "Denervation in the primary olfactory pathway of mice. II. Effects on carnosine and other amine compounds. Carnosine (beta-alanyl-histidine) is present in the olfactory bulb and olfactory eqithelium of mice and rats at 1-2 nmole/mg tissue. Peripheral deafferentation or central denervation causes a rapid, selective decrease of this depeptide from the reciprocal portion of the primary olfactory pathway. These data demonstrate the localization of carnosine within the primary olfactory chemoreceptor neurons and suggest a possible role for this compound in neural transmission."} {"id": "PMID:167915", "title": "A possible non-oncogenic effect of C type bone cell virus on serum calcium levels of potentially leukemic mice.", "content": "In bone of C3H/Fg mice, particles structurally identical to C-type leukemia virus arise from membranes of osteocytes and osteoblasts. Although these virus apparently do not induce morphologic or neoplastic change in bone they may have other, more subtle, effects. Thus, comparison of sera from male C3H/Fg mice, a high leukemia-prone strain, with C57BL and C3H/HeJ mice, low leukemia strains which do not contain C-type virus in bone, reveals that serum calcium levels are significantly lower in the former than in the latter. Further, when C3H/Fg mice develop frank leukemia there is a corresponding increase in virus particles while the serum calcium concentration levels fall to even lower values. The presence of leukemia itself appears not to be the cause as indicated by the failure of implanted lymphocytic leukemic cells in C3H/Fg mice to significantly affect serum calcium concentration. It is postulated that the effects of the virus could be due either to increased osteo blastic activity or to inhibition of osteocytic osteolytic activity or to both.", "contents": "A possible non-oncogenic effect of C type bone cell virus on serum calcium levels of potentially leukemic mice. In bone of C3H/Fg mice, particles structurally identical to C-type leukemia virus arise from membranes of osteocytes and osteoblasts. Although these virus apparently do not induce morphologic or neoplastic change in bone they may have other, more subtle, effects. Thus, comparison of sera from male C3H/Fg mice, a high leukemia-prone strain, with C57BL and C3H/HeJ mice, low leukemia strains which do not contain C-type virus in bone, reveals that serum calcium levels are significantly lower in the former than in the latter. Further, when C3H/Fg mice develop frank leukemia there is a corresponding increase in virus particles while the serum calcium concentration levels fall to even lower values. The presence of leukemia itself appears not to be the cause as indicated by the failure of implanted lymphocytic leukemic cells in C3H/Fg mice to significantly affect serum calcium concentration. It is postulated that the effects of the virus could be due either to increased osteo blastic activity or to inhibition of osteocytic osteolytic activity or to both."} {"id": "PMID:167916", "title": "Comparison of whole calvarial bones and long bones during early growth in rats. Histology and collagen composition.", "content": "The distribution of ossified collagen (bone) and uncalcified collagen (fibrous tissue and cartilage) was compared histologically for rat and dog calvaria at birth. The relative amount of bone and uncalcified collagen was quantitated morphologically for rat calvaria during the first four weeks of rapid growth. Whereas dog calvaria are essentially ossified at birth, rat calvaria at birth consist mostly of fibrous tissue but rapidly become ossified with growth. Bacterial collagenase was used to separate uncalcified collagen from calcified collagen of whole membranous bones (frontal and parietal) and long bones (femur and humerus) at birth from man, monkey, dog, guinea pig, rabbit and rat. By this means quantitative changes in the relative fractions of the two forms of collagen were determined during the first eight weeks of postnatal growth for each type of rat bone. Quantitative biochemical data on whole rat bones (calvarium, femur, humerus) confirmed measurements based on histology which showed that at birth rat calvaria are mostly uncalcified as compared to other species whose bones are mostly ossified at birth. With growth rat membranous bones ossify more rapidly than long bones.", "contents": "Comparison of whole calvarial bones and long bones during early growth in rats. Histology and collagen composition. The distribution of ossified collagen (bone) and uncalcified collagen (fibrous tissue and cartilage) was compared histologically for rat and dog calvaria at birth. The relative amount of bone and uncalcified collagen was quantitated morphologically for rat calvaria during the first four weeks of rapid growth. Whereas dog calvaria are essentially ossified at birth, rat calvaria at birth consist mostly of fibrous tissue but rapidly become ossified with growth. Bacterial collagenase was used to separate uncalcified collagen from calcified collagen of whole membranous bones (frontal and parietal) and long bones (femur and humerus) at birth from man, monkey, dog, guinea pig, rabbit and rat. By this means quantitative changes in the relative fractions of the two forms of collagen were determined during the first eight weeks of postnatal growth for each type of rat bone. Quantitative biochemical data on whole rat bones (calvarium, femur, humerus) confirmed measurements based on histology which showed that at birth rat calvaria are mostly uncalcified as compared to other species whose bones are mostly ossified at birth. With growth rat membranous bones ossify more rapidly than long bones."} {"id": "PMID:167917", "title": "The effect of a myelin apoprotein on lipid structure: a spin probe study.", "content": "Spin probes, stable free radical derivatives of stearic acid and cholestanone, were used to observe the effects of the \"Folch-Lees\" protein isolated from the white matter of bovine brain on the organization and motion of lipid molecules. The incorporation of the organic solvent soluble form of this protein decreased the tendency of a variety of lipid molecules with zero, positive or negative net charges to arrange themselves close to the normal to the lipid bilayer. The aqueous form of the protein also had a profound chaotropic effect on the molecular geometry of the lipid, but only if the lipids had a net negative charge (the protein has a net positive charge in the pH range investigated). Examination of the ESR spectra indicated that this protein altered the geometry of the lipid structure without causing major changes in the mobility of the individual lipid molecules.", "contents": "The effect of a myelin apoprotein on lipid structure: a spin probe study. Spin probes, stable free radical derivatives of stearic acid and cholestanone, were used to observe the effects of the \"Folch-Lees\" protein isolated from the white matter of bovine brain on the organization and motion of lipid molecules. The incorporation of the organic solvent soluble form of this protein decreased the tendency of a variety of lipid molecules with zero, positive or negative net charges to arrange themselves close to the normal to the lipid bilayer. The aqueous form of the protein also had a profound chaotropic effect on the molecular geometry of the lipid, but only if the lipids had a net negative charge (the protein has a net positive charge in the pH range investigated). Examination of the ESR spectra indicated that this protein altered the geometry of the lipid structure without causing major changes in the mobility of the individual lipid molecules."} {"id": "PMID:167918", "title": "In vitro synthesis of estrogen glucuronides and sulfates by human renal tissue.", "content": "17beta-[6,7-3H]Estradiol (E2) was incubated with slices and homogenates of adult human renal tissue. The metabolites formed were identified by chromatography on DEAE-Sephadex, thin layer chromatography and crystallization with carrier steroids or steroid derivatives. The major metabolites formed by slices were estradiol-17-glucuronide (E217G), estrone sulfate and estradiol-3-sulfate. This is the first report of in vitro synthesis of estrogen sulfates by adult renal tissue. Minor quantities of the 3-glucuronides of estrone and estradiol were also found. An oxygen atmosphere appeared to stimulate the production of E217G. A time study with tissue slices showed similarities between the in vitro pattern of glucuronide synthesis and the excretion pattern of these compounds seen in earlier in vivo studies. Homogenates fortified with uridine diphosphoglucuronic acid formed the same pattern of glucuronide products but in lesser amounts. No sulfates were formed under these conditions. Testosterone did not act as a substrate in the experimental conditions used.", "contents": "In vitro synthesis of estrogen glucuronides and sulfates by human renal tissue. 17beta-[6,7-3H]Estradiol (E2) was incubated with slices and homogenates of adult human renal tissue. The metabolites formed were identified by chromatography on DEAE-Sephadex, thin layer chromatography and crystallization with carrier steroids or steroid derivatives. The major metabolites formed by slices were estradiol-17-glucuronide (E217G), estrone sulfate and estradiol-3-sulfate. This is the first report of in vitro synthesis of estrogen sulfates by adult renal tissue. Minor quantities of the 3-glucuronides of estrone and estradiol were also found. An oxygen atmosphere appeared to stimulate the production of E217G. A time study with tissue slices showed similarities between the in vitro pattern of glucuronide synthesis and the excretion pattern of these compounds seen in earlier in vivo studies. Homogenates fortified with uridine diphosphoglucuronic acid formed the same pattern of glucuronide products but in lesser amounts. No sulfates were formed under these conditions. Testosterone did not act as a substrate in the experimental conditions used."} {"id": "PMID:167919", "title": "Biosynthesis of mitochondrial phospholipids using endogenously generated diglycerides.", "content": "When isolated mitochondria or microsomes from rat liver were treated with phospholipase C, the incorporation of radioactive phospholipid precursors was markedly enhanced, presumably as a result of production of diglycerides by hydrolysis of endogenous phospholipids. Incorporation of CDP[14C]choline into lecithin in rat liver or BHK-21 mitochondria could be attributed to residual contamination from elements of the endoplasmic reticulum, with added diglycerides or with endogenous diglycerides produced by the phospholipase C treatment. A similar stimulation of [gamma32P]ATP incorporation into phospholipids was observed with exogenous or endogenous diglycerides, but the mitochondrial diglyceride kinase in either case was also related to the degree of microsomal contaminants. It was concluded that previous studies showing negligible capacity of mitochondria for lecithin biosynthesis de novo were not explainable on the basis of limited accessibility of added diglycerides, and that formation of phosphatidic acid by diglyceride kinase was not of significance in rat liver mitochondria.", "contents": "Biosynthesis of mitochondrial phospholipids using endogenously generated diglycerides. When isolated mitochondria or microsomes from rat liver were treated with phospholipase C, the incorporation of radioactive phospholipid precursors was markedly enhanced, presumably as a result of production of diglycerides by hydrolysis of endogenous phospholipids. Incorporation of CDP[14C]choline into lecithin in rat liver or BHK-21 mitochondria could be attributed to residual contamination from elements of the endoplasmic reticulum, with added diglycerides or with endogenous diglycerides produced by the phospholipase C treatment. A similar stimulation of [gamma32P]ATP incorporation into phospholipids was observed with exogenous or endogenous diglycerides, but the mitochondrial diglyceride kinase in either case was also related to the degree of microsomal contaminants. It was concluded that previous studies showing negligible capacity of mitochondria for lecithin biosynthesis de novo were not explainable on the basis of limited accessibility of added diglycerides, and that formation of phosphatidic acid by diglyceride kinase was not of significance in rat liver mitochondria."} {"id": "PMID:167920", "title": "Adenovirus type 19 keratoconjunctivitis in Canada.", "content": "We describe an outbreak of epidemic keratoconjunctivitis occurring in Montreal during the winter of 1974. Adenovirus type 19 was the only virus isolated. We confirm the presence of type 19 adenovirus in Canada; it produces severe keratoconjunctivitis. The incubation period, method of spread and clinical findings resemble those seen in outbreaks of type 8 EKC. The prevalence of adenovirus type 19 in the population of Canada is unknown. Although some object to the use of the term EKC for infection caused by adenoviruses other than type 8, we believe that EKC should be regarded as an entity requiring virus isolation and antibody determination to identify the adenovirus type responsible for it.", "contents": "Adenovirus type 19 keratoconjunctivitis in Canada. We describe an outbreak of epidemic keratoconjunctivitis occurring in Montreal during the winter of 1974. Adenovirus type 19 was the only virus isolated. We confirm the presence of type 19 adenovirus in Canada; it produces severe keratoconjunctivitis. The incubation period, method of spread and clinical findings resemble those seen in outbreaks of type 8 EKC. The prevalence of adenovirus type 19 in the population of Canada is unknown. Although some object to the use of the term EKC for infection caused by adenoviruses other than type 8, we believe that EKC should be regarded as an entity requiring virus isolation and antibody determination to identify the adenovirus type responsible for it."} {"id": "PMID:167922", "title": "Effect of immunization with attenuated Mycobacterium bovis (BCG) on experimental herpetic keratitis.", "content": "Mycobacterium bovis (BCG, Pasteur strain) was injected intraperitoneally into guinea pigs and rabbits on the 19th and 5th days prior to the intracorneal inoculation of Herpesvirus hominis. During a three-day and nine-day observation period, respectively, the BCG had no significant effect on the clinical course of the herpetic keratitis and no effect on the titer of virus present in the infected corneas.", "contents": "Effect of immunization with attenuated Mycobacterium bovis (BCG) on experimental herpetic keratitis. Mycobacterium bovis (BCG, Pasteur strain) was injected intraperitoneally into guinea pigs and rabbits on the 19th and 5th days prior to the intracorneal inoculation of Herpesvirus hominis. During a three-day and nine-day observation period, respectively, the BCG had no significant effect on the clinical course of the herpetic keratitis and no effect on the titer of virus present in the infected corneas."} {"id": "PMID:167923", "title": "The effect of caesium on adrenergic transmission in rabbit vas deferens.", "content": "The effect of caesium on the responses of rabbit vas deferens to transmural stimulation was investigated. The tissue responded to transmural stimulation with a phasic spike contraction followed bya sustained contractile response. The sustained response was inhibited by phentolamine and guanethidine and thus apparently results from noradrenaline release from adrenergic nerves. Addition of 2-5mM Cs+ greatly potentiated this secondary response without altering the sensitivity of the tissue to added (minus)-noradrenaline. This potentiation was not due to Cs+ decreasing the neuronal uptake of noradrenaline, or by Cs+ altering prostaglandin synthesis. Addition of 2mM Cs+ significantly increased the amount of (plus or minus)-[3-H] metaraminol released from tissues in response to transmural stimulation (5 Hz). It is suggested that caesium potentiated responses of rabbit vas deferens to transmural stimulation by increasing the amount of transmitter released per nerve impulse, possibly as a result of prolongation of the action potential.", "contents": "The effect of caesium on adrenergic transmission in rabbit vas deferens. The effect of caesium on the responses of rabbit vas deferens to transmural stimulation was investigated. The tissue responded to transmural stimulation with a phasic spike contraction followed bya sustained contractile response. The sustained response was inhibited by phentolamine and guanethidine and thus apparently results from noradrenaline release from adrenergic nerves. Addition of 2-5mM Cs+ greatly potentiated this secondary response without altering the sensitivity of the tissue to added (minus)-noradrenaline. This potentiation was not due to Cs+ decreasing the neuronal uptake of noradrenaline, or by Cs+ altering prostaglandin synthesis. Addition of 2mM Cs+ significantly increased the amount of (plus or minus)-[3-H] metaraminol released from tissues in response to transmural stimulation (5 Hz). It is suggested that caesium potentiated responses of rabbit vas deferens to transmural stimulation by increasing the amount of transmitter released per nerve impulse, possibly as a result of prolongation of the action potential."} {"id": "PMID:167924", "title": "Feedback inhibition of adrenocorticotropin release by corticosterone infusions in the adrenalectomized rat.", "content": "Advantage was taken of a specific and sensitive bioassay for rat plasma adrenocorticotropin (ACTH) based on the dispersion of rat adrenal cells with trysin, to investigate the relationship between plasma corticosterone concentration and inhibition of ACTH release under steady-state conditions achieved by graded rates (0-5.12 mug/min per 100 g body weight) of intravenous infusion of the steroid for 45 min in 28-day adrenalectomized rats. In contrast to prior reports involving suppression of stress-induced ACTH release, the inhibitory effect of corticosterone was shown, under our experimental conditions, to be exerted also on the basal rate of ACTH secretion. Indeed, a slight though not significant decrease of plasma ACTH concentration was observed with the corticosterone infusion rate of 0.64 mg/min per 100 g body weight, and further progressive and highly significant drops in concentration were recorded for infusion rates of 2.56 and 5.12 mg/min per 100 g body weight. An increase of the metabolic clearance rate of corticosterone, observed as a function of the infusion rate, was ascribed to saturation by the steroid of the plasma transcortin binding sites.", "contents": "Feedback inhibition of adrenocorticotropin release by corticosterone infusions in the adrenalectomized rat. Advantage was taken of a specific and sensitive bioassay for rat plasma adrenocorticotropin (ACTH) based on the dispersion of rat adrenal cells with trysin, to investigate the relationship between plasma corticosterone concentration and inhibition of ACTH release under steady-state conditions achieved by graded rates (0-5.12 mug/min per 100 g body weight) of intravenous infusion of the steroid for 45 min in 28-day adrenalectomized rats. In contrast to prior reports involving suppression of stress-induced ACTH release, the inhibitory effect of corticosterone was shown, under our experimental conditions, to be exerted also on the basal rate of ACTH secretion. Indeed, a slight though not significant decrease of plasma ACTH concentration was observed with the corticosterone infusion rate of 0.64 mg/min per 100 g body weight, and further progressive and highly significant drops in concentration were recorded for infusion rates of 2.56 and 5.12 mg/min per 100 g body weight. An increase of the metabolic clearance rate of corticosterone, observed as a function of the infusion rate, was ascribed to saturation by the steroid of the plasma transcortin binding sites."} {"id": "PMID:167925", "title": "Phosphorylation of the membrane components of chromaffin granules: synthesis of diphosphatidylinositol and presence of phosphatidylinositol kinase in granule membranes.", "content": "Adenosine triphosphate (ATP) induces the release of catecholamines, endogenous ATP, and soluble protein from chromaffin granules isolated from the adrenal medulla. When ATP exerts this action, it is hydrolyzed by enzymes present in the granule membrane, and part of the Pi liberated from ATP is transferred to the protein and lipid of the granule membrane. The phosphorylated lipid component, which was identified by thin-layer and ion-exchange chromatography as diphosphatidylinositol, was formed from ATP and monophosphatidylinositol. This latter phospholipid was the substrate for the enzyme phosphatidylinositol kinase. Both substrate and enzyme are components of the granule membranes, because they have a similar subcellular distribution as dopamine beta-hydroxylase (a granule membrane marker). The formation of diphosphatidylinositol was Mg(2 plus)-dependent, it was further stimulated by Mn(2 plus), it was inhibited by N-ethylmaleimide and the reaction had an optimal pH of 5. The synthesis of diphosphatidylinositol was also shown to occur in chromaffin granules \"in situ\". during the stimulation of the adrenal medulla by acetylcholine.", "contents": "Phosphorylation of the membrane components of chromaffin granules: synthesis of diphosphatidylinositol and presence of phosphatidylinositol kinase in granule membranes. Adenosine triphosphate (ATP) induces the release of catecholamines, endogenous ATP, and soluble protein from chromaffin granules isolated from the adrenal medulla. When ATP exerts this action, it is hydrolyzed by enzymes present in the granule membrane, and part of the Pi liberated from ATP is transferred to the protein and lipid of the granule membrane. The phosphorylated lipid component, which was identified by thin-layer and ion-exchange chromatography as diphosphatidylinositol, was formed from ATP and monophosphatidylinositol. This latter phospholipid was the substrate for the enzyme phosphatidylinositol kinase. Both substrate and enzyme are components of the granule membranes, because they have a similar subcellular distribution as dopamine beta-hydroxylase (a granule membrane marker). The formation of diphosphatidylinositol was Mg(2 plus)-dependent, it was further stimulated by Mn(2 plus), it was inhibited by N-ethylmaleimide and the reaction had an optimal pH of 5. The synthesis of diphosphatidylinositol was also shown to occur in chromaffin granules \"in situ\". during the stimulation of the adrenal medulla by acetylcholine."} {"id": "PMID:167926", "title": "The demonstration of transmissible gastroenteritis viral antigens by immunoelectrophoresis and counterimmunoelectrophoresis.", "content": "Immunoelectrophoresis of alkaline intestinal extracts, or the supernatants after precipitation of these extracts with 60% ammonium sulfate, prepared from piglets experimentally infected with the DL or Purdue strains of transmissible gastroenteritis virus, revealed up to three antigens. Two antigens migrated towards the anode, and the third migrated towards the cathode. Antigens with anodal or cathodal mobility were also demonstrated in the same materials by counterimmunoelectrophoresis, and the procedure for counterimmunoelectrophoresis was modified to detect both antigens in a single test.", "contents": "The demonstration of transmissible gastroenteritis viral antigens by immunoelectrophoresis and counterimmunoelectrophoresis. Immunoelectrophoresis of alkaline intestinal extracts, or the supernatants after precipitation of these extracts with 60% ammonium sulfate, prepared from piglets experimentally infected with the DL or Purdue strains of transmissible gastroenteritis virus, revealed up to three antigens. Two antigens migrated towards the anode, and the third migrated towards the cathode. Antigens with anodal or cathodal mobility were also demonstrated in the same materials by counterimmunoelectrophoresis, and the procedure for counterimmunoelectrophoresis was modified to detect both antigens in a single test."} {"id": "PMID:167927", "title": "Virus survival on inanimate surfaces.", "content": "The persistence of several types of viruses on hard, inanimate surfaces under different relative humidities, temperatures, and types of surfaces was investigated. No differences in survival on glass, vinyl asbestos tile, ceramic tile, and stainless steel were found. Under conditions of low humidity and room temperature, adenovirus, poliovirus, and herpes simplex virus survived for at least 8 weeks. Vaccinia and coxsackie viruses survived for at least 2 weeks but differences due to surfaces found in many environments, in addition to the laboratory, emphasizes the possible role of hard surfaces in the transmission of viruses.", "contents": "Virus survival on inanimate surfaces. The persistence of several types of viruses on hard, inanimate surfaces under different relative humidities, temperatures, and types of surfaces was investigated. No differences in survival on glass, vinyl asbestos tile, ceramic tile, and stainless steel were found. Under conditions of low humidity and room temperature, adenovirus, poliovirus, and herpes simplex virus survived for at least 8 weeks. Vaccinia and coxsackie viruses survived for at least 2 weeks but differences due to surfaces found in many environments, in addition to the laboratory, emphasizes the possible role of hard surfaces in the transmission of viruses."} {"id": "PMID:167928", "title": "Aerobic adaptation in yeast. II. Changes in enzyme profiles during a step-down anaerobic-aerobic transfer.", "content": "The levels of various enzymes and components of the glycolytic and respiratory pathways of the yeast Saccharomyces cerevisiae have been determined during a step-down, anaerobic-to-aerobic transition. These activities were determined as an adjunct to the respective metabolite data reported in the first paper in this series. It is clear from the data that anaerobic conditions induce an environment conducive to express glycolytic enzyme activities, while manifesting a differential induction/repression effect on oxidative enzymes. An NAD/NADH mediated mechanism is proposed to explain this difference. Of the enzymes assayed only cytochrome c oxidase shows any direct response to oxygen challenge and consequently it is suggested that the assembly of this enzyme is the trigger mechanism and rate-limiting step in aerobic adaptation.", "contents": "Aerobic adaptation in yeast. II. Changes in enzyme profiles during a step-down anaerobic-aerobic transfer. The levels of various enzymes and components of the glycolytic and respiratory pathways of the yeast Saccharomyces cerevisiae have been determined during a step-down, anaerobic-to-aerobic transition. These activities were determined as an adjunct to the respective metabolite data reported in the first paper in this series. It is clear from the data that anaerobic conditions induce an environment conducive to express glycolytic enzyme activities, while manifesting a differential induction/repression effect on oxidative enzymes. An NAD/NADH mediated mechanism is proposed to explain this difference. Of the enzymes assayed only cytochrome c oxidase shows any direct response to oxygen challenge and consequently it is suggested that the assembly of this enzyme is the trigger mechanism and rate-limiting step in aerobic adaptation."} {"id": "PMID:167929", "title": "Aerobic adaptation in yeast, IV. Alterations in enzyme synthesis during anaerobic-aerobic transitions in exponentially growing cultures.", "content": "As a corollary to the metabolite data obtained from yeast cultures undergoing an exponential anaerobic-aerobic phase transition, levels of various glycolytic and citric acid cycle enzyme activities have been monitored in these cells. The relation of the changes in these enzyme activities in cells grown on either glucose or galactose is discussed on light of different metabolic postures these cells demonstrate as a result of their transitions. A general discussion is presented which compares the results obtained in this series of papers from both step-down and exponential transfer experiments and relates these data to control of mitochondriogenesis in yeast.", "contents": "Aerobic adaptation in yeast, IV. Alterations in enzyme synthesis during anaerobic-aerobic transitions in exponentially growing cultures. As a corollary to the metabolite data obtained from yeast cultures undergoing an exponential anaerobic-aerobic phase transition, levels of various glycolytic and citric acid cycle enzyme activities have been monitored in these cells. The relation of the changes in these enzyme activities in cells grown on either glucose or galactose is discussed on light of different metabolic postures these cells demonstrate as a result of their transitions. A general discussion is presented which compares the results obtained in this series of papers from both step-down and exponential transfer experiments and relates these data to control of mitochondriogenesis in yeast."} {"id": "PMID:167930", "title": "Ultrastructure of the Alnus crispa var. mollis Fern. root nodule endophyte.", "content": "Nitrogen-fixing, field-obtained root nodules of the silky green alder were studied by transmission electron microscopy. The nodule endophyte exhibited a prokaryotic cytology and was present in two forms: the hypha(0.3-1.0mum), which was branched and septate, and the vesicle (3-5mum), which was also septate and developed at the parental hypha tip. Bacteria-like cells, previously observed in light microscopy studies, were not seen in the present work. The actinomycete-like endophyte penetrated through the host cell wall and becane enveloped by a capsular material (0.1mum), the whole being enclosed by host membranes. In some host cells, the endophyte appeared to lyse and become a mass of shrunken debris. The fine structure of the Alnus crispa var. mollis root nodule endophyte was found to be similar to that of other nonleguminous root nodule endophytes.", "contents": "Ultrastructure of the Alnus crispa var. mollis Fern. root nodule endophyte. Nitrogen-fixing, field-obtained root nodules of the silky green alder were studied by transmission electron microscopy. The nodule endophyte exhibited a prokaryotic cytology and was present in two forms: the hypha(0.3-1.0mum), which was branched and septate, and the vesicle (3-5mum), which was also septate and developed at the parental hypha tip. Bacteria-like cells, previously observed in light microscopy studies, were not seen in the present work. The actinomycete-like endophyte penetrated through the host cell wall and becane enveloped by a capsular material (0.1mum), the whole being enclosed by host membranes. In some host cells, the endophyte appeared to lyse and become a mass of shrunken debris. The fine structure of the Alnus crispa var. mollis root nodule endophyte was found to be similar to that of other nonleguminous root nodule endophytes."} {"id": "PMID:167931", "title": "An immunoprecipitin study of the incidence of influenza A antibodies in animal sera in the Ottawa area.", "content": "A survey of over 600 'normal' sera from 14 animal species by immunoprecipitin tests in cellulose acetate using viron antigens revealed a high incidence of precipitating activity against a broad range of influenza A virus strains, particularly A2hHong Kong/1/68 and /PR8. However, serum treatments trypsin-heat-periodate, NaIO4, V. cholerae receptor-destroying enzyme (RDE), or kaolin eliminated most precipitating activity, which suggests that it was due to \"non-specific\" inhibitors of influenze viruses. A resistant minority could not be identified as inhibitor or antibody on this basis. Precipitation of the influenza A major type-specific antigen in virus-soluble antigens by human 7S gamma globulin antibody (IgG), demonstrated to be specific for influenza virus, was established as a reference reaction to identify similar immunoprecipitin reactions occurring between virus-soluble antigens and normal or immune sera. Complement fixation tests provided supplementary evidence for the presence of influenza A antibodies in these sera. Influenza A antibodies were found in only a few sera of six animal species: cat, dog, rabbit, goat, chipmunk, and sheep. Thus the animal species examined in the Ottawa area have not revealed an unequivocal reservoir for human influenza A viruses.", "contents": "An immunoprecipitin study of the incidence of influenza A antibodies in animal sera in the Ottawa area. A survey of over 600 'normal' sera from 14 animal species by immunoprecipitin tests in cellulose acetate using viron antigens revealed a high incidence of precipitating activity against a broad range of influenza A virus strains, particularly A2hHong Kong/1/68 and /PR8. However, serum treatments trypsin-heat-periodate, NaIO4, V. cholerae receptor-destroying enzyme (RDE), or kaolin eliminated most precipitating activity, which suggests that it was due to \"non-specific\" inhibitors of influenze viruses. A resistant minority could not be identified as inhibitor or antibody on this basis. Precipitation of the influenza A major type-specific antigen in virus-soluble antigens by human 7S gamma globulin antibody (IgG), demonstrated to be specific for influenza virus, was established as a reference reaction to identify similar immunoprecipitin reactions occurring between virus-soluble antigens and normal or immune sera. Complement fixation tests provided supplementary evidence for the presence of influenza A antibodies in these sera. Influenza A antibodies were found in only a few sera of six animal species: cat, dog, rabbit, goat, chipmunk, and sheep. Thus the animal species examined in the Ottawa area have not revealed an unequivocal reservoir for human influenza A viruses."} {"id": "PMID:167932", "title": "Patterns of motoneuron dysfunction and recovery.", "content": "Electrophysiological studies have been carried out on five patients with neuropathies of different etiologies. In each patient serial estimates were made of the numbers of functioning motor units in various muscles. It was found that the intensity of the neuropathic process and the rate of recovery differed in a consistent way among the motoneuron pools investigated. The lesion was more severe in extensor digitorum brevis neurons than in thenar neurons, while the hypothenar ones were least affected. A stage of partial synaptic failure has been recognized in which a motoneuron appears to be no longer able to excite a muscle fiber, but still capable of maintaining certain trophic activities. By comparing the number of functioning motor units with the size of the maximum evoked muscle response it has been possible to detect the adoption of denervated muscle fibers by axonal sprouts from 'healthy' surviving neurons (collateral reinnervation). Lastly, in some muscles it appears that the adopted muscle fibers may subsequently be recaptured by the original motoneurons following recovery of the latter from the neurotoxic insult.", "contents": "Patterns of motoneuron dysfunction and recovery. Electrophysiological studies have been carried out on five patients with neuropathies of different etiologies. In each patient serial estimates were made of the numbers of functioning motor units in various muscles. It was found that the intensity of the neuropathic process and the rate of recovery differed in a consistent way among the motoneuron pools investigated. The lesion was more severe in extensor digitorum brevis neurons than in thenar neurons, while the hypothenar ones were least affected. A stage of partial synaptic failure has been recognized in which a motoneuron appears to be no longer able to excite a muscle fiber, but still capable of maintaining certain trophic activities. By comparing the number of functioning motor units with the size of the maximum evoked muscle response it has been possible to detect the adoption of denervated muscle fibers by axonal sprouts from 'healthy' surviving neurons (collateral reinnervation). Lastly, in some muscles it appears that the adopted muscle fibers may subsequently be recaptured by the original motoneurons following recovery of the latter from the neurotoxic insult."} {"id": "PMID:167933", "title": "Clinical usefulness of gastric acidity studies.", "content": "Tests of gastric secretion are seldom diagnostic in the investigation of gastric and duodenal ulceration, but they can provide evidence that is helpful in arriving at a diagnosis. Common tests include basal acid output, pentagastrin-stimulated maximal and peak acid output, and the Hollander test. There is some evidence that they may be useful in selecting the type of operation for peptic ulceration. Indications for performing these tests relate to the Zollinger-Ellison syndrome, duodenal ulcer, recurrent dyspepsia after operation for duodenal ulcer, and decisions concerning the choice of operation for peptic ulcer. In order to perform these functions they must be properly conducted and interpreted; they are simply an adjunct to clinical judgement, and complementary to other laboratory tests.", "contents": "Clinical usefulness of gastric acidity studies. Tests of gastric secretion are seldom diagnostic in the investigation of gastric and duodenal ulceration, but they can provide evidence that is helpful in arriving at a diagnosis. Common tests include basal acid output, pentagastrin-stimulated maximal and peak acid output, and the Hollander test. There is some evidence that they may be useful in selecting the type of operation for peptic ulceration. Indications for performing these tests relate to the Zollinger-Ellison syndrome, duodenal ulcer, recurrent dyspepsia after operation for duodenal ulcer, and decisions concerning the choice of operation for peptic ulcer. In order to perform these functions they must be properly conducted and interpreted; they are simply an adjunct to clinical judgement, and complementary to other laboratory tests."} {"id": "PMID:167934", "title": "Unilateral hypoglossal nerve atrophy as a late complication of radiation therapy ofhead and neck carcinoma: a report of four cases and a review of the literature on peripheral and cranial nerve damages after radiation therapy.", "content": "The case histories of four patients who developed hemiatrophy of the tongue from 3 to9 years after a course of curative radiation therapy for carcinomas of the head and neck are presented. These patients subsequently followed for from 1 1/2 to 6 years withoutlocal recurrence of the tumor, distant metastasis, or involvement of other cranial nerves, indicative of only a unilateral hypoglossal nerve atrophy. A review of the literatureshowed that peripheral and cranial nerve damages after radiation therapy have been reported for the optic nerve, hypoglossal nerve, oculomotor nerve, abducens nerve, recurrent laryngeal nerve, brachial plexus nerves and peripheral nerves of the extremeties. Reviewof clinical and experimental data indicated that in most cases, the damages were probably caused by extensive connective tissue fibrosis around and infiltrating the nerve trunks. Three possible types of peripheral and cranial nerve damages after radiation therapy are identified.", "contents": "Unilateral hypoglossal nerve atrophy as a late complication of radiation therapy ofhead and neck carcinoma: a report of four cases and a review of the literature on peripheral and cranial nerve damages after radiation therapy. The case histories of four patients who developed hemiatrophy of the tongue from 3 to9 years after a course of curative radiation therapy for carcinomas of the head and neck are presented. These patients subsequently followed for from 1 1/2 to 6 years withoutlocal recurrence of the tumor, distant metastasis, or involvement of other cranial nerves, indicative of only a unilateral hypoglossal nerve atrophy. A review of the literatureshowed that peripheral and cranial nerve damages after radiation therapy have been reported for the optic nerve, hypoglossal nerve, oculomotor nerve, abducens nerve, recurrent laryngeal nerve, brachial plexus nerves and peripheral nerves of the extremeties. Reviewof clinical and experimental data indicated that in most cases, the damages were probably caused by extensive connective tissue fibrosis around and infiltrating the nerve trunks. Three possible types of peripheral and cranial nerve damages after radiation therapy are identified."} {"id": "PMID:167938", "title": "Complete and apparently specif local tumor regression using syngeneic or xenogeneic \"tumor-immune\" RNA extracts.", "content": "Syngeneic and xenogeneic RNA-rich extracts of lymphoid tissues were used in an immunotherapeutic regimen to treat strain 2 guinea pigs that were given intradermal injections of a uniformly lethal dose (1 x 10(6)) of line 10 diethylnitrosamine-induced transplantable hepatoma cells. When 1 X 10(7) syngeneic nonsensitive peritoneal exudate cells, 2.5 mg RNA from line 10-immune strain 2 guinea pigs or line 10-immune Rhesus monkeys, and 1.0 mg of a line-10 tumor-specific antigen preparation were injected s.c. under the tumor cells injected 5 days previously, complete local tumor regression in all treated animals was observed. If either nonsensitive peritoneal exudate cells, RNA, or line 10 tumor-specific antigen was omitted, or if Escherichia coli RNA or RNA from animals sensitized to a different tumor (line 1) was used, little or no tumor regression was observed, suggesting that the action of the RNA may have resulted in an antitumor response specific for the noplasm being treated. The long-term tumor-free survival of all treated animals indicates that the action of the RNA is systemic, since metastases are known to occur frequently by the time our therapeutic regimen was given. Also, in testing the biological activity of the \"tumor-immune\" RNA in the in vitro cell-migration-inhibition assay, both the syngeneic and xenogeneic RNA extracts could transfer tumor-specific immunological sensitivity, as demonstrated by the elaboration of migration-inhibitory factor by the RNA-treated nonsensitive peritonial exudate cells in the presence of the line 10 tumor-specific antigen.", "contents": "Complete and apparently specif local tumor regression using syngeneic or xenogeneic \"tumor-immune\" RNA extracts. Syngeneic and xenogeneic RNA-rich extracts of lymphoid tissues were used in an immunotherapeutic regimen to treat strain 2 guinea pigs that were given intradermal injections of a uniformly lethal dose (1 x 10(6)) of line 10 diethylnitrosamine-induced transplantable hepatoma cells. When 1 X 10(7) syngeneic nonsensitive peritoneal exudate cells, 2.5 mg RNA from line 10-immune strain 2 guinea pigs or line 10-immune Rhesus monkeys, and 1.0 mg of a line-10 tumor-specific antigen preparation were injected s.c. under the tumor cells injected 5 days previously, complete local tumor regression in all treated animals was observed. If either nonsensitive peritoneal exudate cells, RNA, or line 10 tumor-specific antigen was omitted, or if Escherichia coli RNA or RNA from animals sensitized to a different tumor (line 1) was used, little or no tumor regression was observed, suggesting that the action of the RNA may have resulted in an antitumor response specific for the noplasm being treated. The long-term tumor-free survival of all treated animals indicates that the action of the RNA is systemic, since metastases are known to occur frequently by the time our therapeutic regimen was given. Also, in testing the biological activity of the \"tumor-immune\" RNA in the in vitro cell-migration-inhibition assay, both the syngeneic and xenogeneic RNA extracts could transfer tumor-specific immunological sensitivity, as demonstrated by the elaboration of migration-inhibitory factor by the RNA-treated nonsensitive peritonial exudate cells in the presence of the line 10 tumor-specific antigen."} {"id": "PMID:167935", "title": "Antitumor activity of selected amino acid derivatives against various tumor systems.", "content": "We have previously reported that from 350 amino acid (A-A) derivatives five were selected after the primary in vivo and in vitro screening tests. The five compounds which were found to possess potential antitumor activity against Ehrlich ascites carcinoma are as follows: beta-naphthalene-sulfonyl-DL-tryptophan (A-91), beta-naphthyl-aminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), n-9-fluorenylactyl-L-phenylalanine (A-192), and N-propoinyl-L-valine (A-195). The effect on life prolongation and tumor growth of these selected A-A derivatives against various types of tumors, including ascites and solid tumors in mice and ascites hepatomas in rats, was examined. A-A derivatives were administered once daily 3 consecutive days starting 24 hours after tumor implantation. Experimental results showed that among the five A-A derivatives possessing considerable activity against Ehlich carcinoma, A-144 and A-145 were found to be more effective than chromomycin A and showed activity similar to that of cyclophosphamide against ascites Sarcoma 180. A-A derivatives showed slight antitumor activity against SR61 and L1210 leukemias. In rat ascites hepatoma, such as AH13, AH7974, AH60C, and Yoshida sarcoma, only A-145 showed a significant prolongation of the lifespan in the control groups. The five selected A-A derivatives significantly inhibited the growth of Nakahara-Fukuoka sarcoma and solid Sarcoma 180. These findings indicate that among the five A-A derivatives, A-15 appeared to be the most active against ascites and solid tumors.", "contents": "Antitumor activity of selected amino acid derivatives against various tumor systems. We have previously reported that from 350 amino acid (A-A) derivatives five were selected after the primary in vivo and in vitro screening tests. The five compounds which were found to possess potential antitumor activity against Ehrlich ascites carcinoma are as follows: beta-naphthalene-sulfonyl-DL-tryptophan (A-91), beta-naphthyl-aminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), n-9-fluorenylactyl-L-phenylalanine (A-192), and N-propoinyl-L-valine (A-195). The effect on life prolongation and tumor growth of these selected A-A derivatives against various types of tumors, including ascites and solid tumors in mice and ascites hepatomas in rats, was examined. A-A derivatives were administered once daily 3 consecutive days starting 24 hours after tumor implantation. Experimental results showed that among the five A-A derivatives possessing considerable activity against Ehlich carcinoma, A-144 and A-145 were found to be more effective than chromomycin A and showed activity similar to that of cyclophosphamide against ascites Sarcoma 180. A-A derivatives showed slight antitumor activity against SR61 and L1210 leukemias. In rat ascites hepatoma, such as AH13, AH7974, AH60C, and Yoshida sarcoma, only A-145 showed a significant prolongation of the lifespan in the control groups. The five selected A-A derivatives significantly inhibited the growth of Nakahara-Fukuoka sarcoma and solid Sarcoma 180. These findings indicate that among the five A-A derivatives, A-15 appeared to be the most active against ascites and solid tumors."} {"id": "PMID:167939", "title": "Changes in lactate dehydrogenase enzyme pattern in Chinese hamster cells infected and transformed with Simian virus 40.", "content": "The lactate dehydrogenase (LDH) isozyme patterns of consecutive passages of Chinese hamster embryo cultures were monitored. At early passages the population displayed two LDH bands, M4 and M3H; however, at higher passages the cultures exhibited M2H2, M2H, and M4. When primary cultures of Chinese hamster embryo cells were infected with simian virus 40 (SV40), no change in the LDH pattern was observed; however, the total activity of LDH increased. Twenty-three of 25 transformed colonies isolated from SV40-infected primary cells by their ability to grow in methyl cellulose produced only M4 or M4-M3H isozymes bands. Four of the SV40-transformed clones that produced only the M4 isozyme were tested for LDH activity and found to have activities 2.5 to 3 times greater than the control cells. Chinese hamster kidney epithelial cells transformed with SV40 virus had a decrease in the H subunit production, from 57 to 31%, compared with normal kidney epithelial cells. This decrease in H subunit production led to an increase in the cathode-migrating isozymes. Therefore, a shift to the cathode-migrating isozyme was observed in SV40-transformed cells. This change in LDH pattern might represent a reversion to the enzyme pattern present in fetal cells.", "contents": "Changes in lactate dehydrogenase enzyme pattern in Chinese hamster cells infected and transformed with Simian virus 40. The lactate dehydrogenase (LDH) isozyme patterns of consecutive passages of Chinese hamster embryo cultures were monitored. At early passages the population displayed two LDH bands, M4 and M3H; however, at higher passages the cultures exhibited M2H2, M2H, and M4. When primary cultures of Chinese hamster embryo cells were infected with simian virus 40 (SV40), no change in the LDH pattern was observed; however, the total activity of LDH increased. Twenty-three of 25 transformed colonies isolated from SV40-infected primary cells by their ability to grow in methyl cellulose produced only M4 or M4-M3H isozymes bands. Four of the SV40-transformed clones that produced only the M4 isozyme were tested for LDH activity and found to have activities 2.5 to 3 times greater than the control cells. Chinese hamster kidney epithelial cells transformed with SV40 virus had a decrease in the H subunit production, from 57 to 31%, compared with normal kidney epithelial cells. This decrease in H subunit production led to an increase in the cathode-migrating isozymes. Therefore, a shift to the cathode-migrating isozyme was observed in SV40-transformed cells. This change in LDH pattern might represent a reversion to the enzyme pattern present in fetal cells."} {"id": "PMID:167940", "title": "Isolation of variant cells from SV-40 transformed human diploid fibroblasts.", "content": "Variant cell lines that are sensitive to density-dependent inhibition of growth have been isolated from three of four SV40-transformed human fibroblast cell lines. Variants were isolated by plating the transformed cells at low density, by treating them with 5-fluorodeoxyuridine, or by growing them on glutaraldehyde-fixed monolayers of normal cells. The variant cell lines, isolated at a frequency of about 2% of all cells forming colonies after treatment, were initially recognized by colonial morphology, and the variant pheno-types were confirmed, after subculturing, by saturation-density determinations. The variant cell lines reach saturation densities that are 40% or less than those of the parent cell lines, and plate in soft agar medium at reduced efficiency, compared with the parent cells. They retain SV40 T antigen. The modal chromosome numbers of two of the variant cell lines were increased, compared with those of the parent cell lines; two other variants were indistinguishable in chromosome number from the parent cells. Stability of these properties over a 6-month period was demonstrated with two of the variants.", "contents": "Isolation of variant cells from SV-40 transformed human diploid fibroblasts. Variant cell lines that are sensitive to density-dependent inhibition of growth have been isolated from three of four SV40-transformed human fibroblast cell lines. Variants were isolated by plating the transformed cells at low density, by treating them with 5-fluorodeoxyuridine, or by growing them on glutaraldehyde-fixed monolayers of normal cells. The variant cell lines, isolated at a frequency of about 2% of all cells forming colonies after treatment, were initially recognized by colonial morphology, and the variant pheno-types were confirmed, after subculturing, by saturation-density determinations. The variant cell lines reach saturation densities that are 40% or less than those of the parent cell lines, and plate in soft agar medium at reduced efficiency, compared with the parent cells. They retain SV40 T antigen. The modal chromosome numbers of two of the variant cell lines were increased, compared with those of the parent cell lines; two other variants were indistinguishable in chromosome number from the parent cells. Stability of these properties over a 6-month period was demonstrated with two of the variants."} {"id": "PMID:167936", "title": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) in the treatment of solid tumors in children.", "content": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) was administered to 46 children with various solid tumors which were resistant to conventional therapy. Two or more courses of NSC-45388 were administered to 13 of 18 children with neuroblastoma, seven of 11 children with rhabdomyosarcoma, three of four children with Wilms' tumor, one of three children with Ewing's tumor, and six of ten children with miscellaneous neoplastic disorders. Major toxic effects included nausea, vomiting, decreased hemoglobin level, thrombocytopenia, and leukopenia. A therapeutic regimen of 200-450 mg/m2/day for 5 consecutive days can be administered safely every 22 days. Objective responses were observed in three children with neuroblastoma and in one child with rhabdomyosarcoma. This drug has minimal but definite activity as a single agent in children with advanced neuroblastoma and rhabdomyosarcoma and should be evaluated further in combination therapy.", "contents": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) in the treatment of solid tumors in children. 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) was administered to 46 children with various solid tumors which were resistant to conventional therapy. Two or more courses of NSC-45388 were administered to 13 of 18 children with neuroblastoma, seven of 11 children with rhabdomyosarcoma, three of four children with Wilms' tumor, one of three children with Ewing's tumor, and six of ten children with miscellaneous neoplastic disorders. Major toxic effects included nausea, vomiting, decreased hemoglobin level, thrombocytopenia, and leukopenia. A therapeutic regimen of 200-450 mg/m2/day for 5 consecutive days can be administered safely every 22 days. Objective responses were observed in three children with neuroblastoma and in one child with rhabdomyosarcoma. This drug has minimal but definite activity as a single agent in children with advanced neuroblastoma and rhabdomyosarcoma and should be evaluated further in combination therapy."} {"id": "PMID:167941", "title": "Carcinogenicity of nitrosation products of ephedrine, sarcosine, folic acid, and creatinine.", "content": "Carcinogenic activity of several synthetic N-nitroso compounds was evaluated in C57BL/6J X C3HeB/FeJ F1 mice. Test substances, suspended in trioctanoin, were injected i.p. in three equal doses given on Days 1, 4, and 7 after birth and animals were held without further treatment for up to 85 weeks. Nitrosoephedrine at a total dose of 600 mg/kg induced metastasizing liver cell carcinomas in 28 of 30 animals. Nitrososarcosine (225 mg/kg) induced similar tumors in 8 of 14 animals. Nitrosofolic acid (375 mg/kg) induced lung adenocarcinomas in 4 of 28 mice. Creatinine-5-oxime (600 mg/kg) showed no evidence of carcinogenic activity. Diethylnitrosamine (12 mg/kg given in four doses), included as a positive control, caused metastasizing liver cell tumors in 23 of 25 animals.", "contents": "Carcinogenicity of nitrosation products of ephedrine, sarcosine, folic acid, and creatinine. Carcinogenic activity of several synthetic N-nitroso compounds was evaluated in C57BL/6J X C3HeB/FeJ F1 mice. Test substances, suspended in trioctanoin, were injected i.p. in three equal doses given on Days 1, 4, and 7 after birth and animals were held without further treatment for up to 85 weeks. Nitrosoephedrine at a total dose of 600 mg/kg induced metastasizing liver cell carcinomas in 28 of 30 animals. Nitrososarcosine (225 mg/kg) induced similar tumors in 8 of 14 animals. Nitrosofolic acid (375 mg/kg) induced lung adenocarcinomas in 4 of 28 mice. Creatinine-5-oxime (600 mg/kg) showed no evidence of carcinogenic activity. Diethylnitrosamine (12 mg/kg given in four doses), included as a positive control, caused metastasizing liver cell tumors in 23 of 25 animals."} {"id": "PMID:167937", "title": "Chemotherapeutic management of bronchogenic carcinoma: trials with NSC-140117, a new methanesulfonic acid ester of aminoglycol.", "content": "A new drug, NSC-140117, was used in the management of 15 patients who had late bronchogenic carcinoma and were unable to receive surgical or radiotherapeutic treatment. Good responses in the form of 90% shrinkage in the size of the lesionswere encountered in nine patients (60%). Response is still being maintained from 6 months to 1.5 years after the start of therapy. No toxic effects, including hematopoietic toxicity, were encountered.", "contents": "Chemotherapeutic management of bronchogenic carcinoma: trials with NSC-140117, a new methanesulfonic acid ester of aminoglycol. A new drug, NSC-140117, was used in the management of 15 patients who had late bronchogenic carcinoma and were unable to receive surgical or radiotherapeutic treatment. Good responses in the form of 90% shrinkage in the size of the lesionswere encountered in nine patients (60%). Response is still being maintained from 6 months to 1.5 years after the start of therapy. No toxic effects, including hematopoietic toxicity, were encountered."} {"id": "PMID:167942", "title": "Ultrastructural characteristics of human neurilemoma cell nuclei.", "content": "Nuclei of human neurilemoma cells exhibit deep and extensive invaginations of part of their surface. Such invaginations contain cytoplasmic matter. However, in areas of the nucleoplasm distant from the invaginations, small membrane-bound bodies, some of which contain a \"nucleoid,\" occur either singly or grouped together and enclosed within a large membrane body. These small bodies are not considered virus-like. Degenerated nuclei from cultured tumor tissue contain spherical bodies, 130 to 230 nm in diameter, with spikes on their surface similar to those seen on envelopes of herpes-type viruses. Significance of these bodies in vivo and in vitro tumor tissues is not known.", "contents": "Ultrastructural characteristics of human neurilemoma cell nuclei. Nuclei of human neurilemoma cells exhibit deep and extensive invaginations of part of their surface. Such invaginations contain cytoplasmic matter. However, in areas of the nucleoplasm distant from the invaginations, small membrane-bound bodies, some of which contain a \"nucleoid,\" occur either singly or grouped together and enclosed within a large membrane body. These small bodies are not considered virus-like. Degenerated nuclei from cultured tumor tissue contain spherical bodies, 130 to 230 nm in diameter, with spikes on their surface similar to those seen on envelopes of herpes-type viruses. Significance of these bodies in vivo and in vitro tumor tissues is not known."} {"id": "PMID:167943", "title": "Pancreatic islet-cell and other tumors in rats given heliotrine, a monoester pyrrolizidine alkaloid, and nicotinamide.", "content": "Three rats of six males, surviving 22 to 27.5 months after one or two intragastric doses of the monoester pyrrolizidine alkaloid, heliotrine (230 mg/kg body weight), and pretreatment with nicotinamide (350 mg/kg body weight) by pretreatment with nicotinamide (350 mg/kg body weight) by i.p. injections, developed pancreatic islet-cell tumors, accompanied in one of the rats by transitory cell papillomas of the urinary bladder and interstitial testicular tumors and in another by a hepatoma. The lesions in the livers showed progression from megalocytosis, to microscopic hepatocellular hyperplasia, to increasingly larger nodules and hepatoma. One rat, given heliotrine, but no nicotinamide, also developed adenoma of the pancreatic islet cells. Adenomas of the pituitary were present among the experimental and also among the control rats killed between 19 and 27.5 months after the beginning of the experiment, and they are not likely to have been caused by the alkaloid. Heliotrine, in which the crucial double bond in the pyrrolizidine moiety is sterically hindered, appears to be less readily sequestered by the liver and also to affect other organs. Alkylation of nicotinamide at the N-1 position prevents its being reused for coenzyme biosynthesis. Hence, pretreatment of rats with large doses of nicotinamide prevents the depletion of nicotinamide adenine dinucleotide coenzymes and liver necrosis in rats given heliotrine (230 mg/kg body weight).", "contents": "Pancreatic islet-cell and other tumors in rats given heliotrine, a monoester pyrrolizidine alkaloid, and nicotinamide. Three rats of six males, surviving 22 to 27.5 months after one or two intragastric doses of the monoester pyrrolizidine alkaloid, heliotrine (230 mg/kg body weight), and pretreatment with nicotinamide (350 mg/kg body weight) by pretreatment with nicotinamide (350 mg/kg body weight) by i.p. injections, developed pancreatic islet-cell tumors, accompanied in one of the rats by transitory cell papillomas of the urinary bladder and interstitial testicular tumors and in another by a hepatoma. The lesions in the livers showed progression from megalocytosis, to microscopic hepatocellular hyperplasia, to increasingly larger nodules and hepatoma. One rat, given heliotrine, but no nicotinamide, also developed adenoma of the pancreatic islet cells. Adenomas of the pituitary were present among the experimental and also among the control rats killed between 19 and 27.5 months after the beginning of the experiment, and they are not likely to have been caused by the alkaloid. Heliotrine, in which the crucial double bond in the pyrrolizidine moiety is sterically hindered, appears to be less readily sequestered by the liver and also to affect other organs. Alkylation of nicotinamide at the N-1 position prevents its being reused for coenzyme biosynthesis. Hence, pretreatment of rats with large doses of nicotinamide prevents the depletion of nicotinamide adenine dinucleotide coenzymes and liver necrosis in rats given heliotrine (230 mg/kg body weight)."} {"id": "PMID:167944", "title": "Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer.", "content": "An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of \"soft\" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, \"scirrhous\" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.", "contents": "Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of \"soft\" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, \"scirrhous\" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth."} {"id": "PMID:167945", "title": "A comparative study of inner membrane enzymes and transport systems in mitochondria from R3230AC mammary tumor and normal rat mammary gland.", "content": "Mitochondria from a rat mammary tumor (R3230AC) have been compared with mitochondria from pregnant and lactating rat mammary glands, with particular attention paid to inner membrane enzymes and Transport proteins. In the tumor the mitochondrial adenosine triphosphatase was not activated by 2,4-dinitrophenol, in contrast to the mammary mitochondria from lactating or pregnant rats. Translocation of adenosine diphosphate across the inner membrane was found to be more rapid in the tumor by virtue of lovered Km adenosine diphosphate and raised Vmax. Transport of phosphate and dicarboxylic acids occurred at similar rates in all three types of mitochondria. The inner membrane proteins were also examined directly by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and some differences are noted. These results, although they indicate subtle differences between the inner mitochondrial membranes of tumor as compared with those of pregnant or lactating rat mammary glands, cannot form the basis of an explanation for enhanced glucose utilization and aerobic lactic acid production in this tumor.", "contents": "A comparative study of inner membrane enzymes and transport systems in mitochondria from R3230AC mammary tumor and normal rat mammary gland. Mitochondria from a rat mammary tumor (R3230AC) have been compared with mitochondria from pregnant and lactating rat mammary glands, with particular attention paid to inner membrane enzymes and Transport proteins. In the tumor the mitochondrial adenosine triphosphatase was not activated by 2,4-dinitrophenol, in contrast to the mammary mitochondria from lactating or pregnant rats. Translocation of adenosine diphosphate across the inner membrane was found to be more rapid in the tumor by virtue of lovered Km adenosine diphosphate and raised Vmax. Transport of phosphate and dicarboxylic acids occurred at similar rates in all three types of mitochondria. The inner membrane proteins were also examined directly by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and some differences are noted. These results, although they indicate subtle differences between the inner mitochondrial membranes of tumor as compared with those of pregnant or lactating rat mammary glands, cannot form the basis of an explanation for enhanced glucose utilization and aerobic lactic acid production in this tumor."} {"id": "PMID:167946", "title": "Turnover of high-molecular-weight cell surface proteins during growth and expression of malignant transformation.", "content": "The turnover of cell surface proteins in normal rat kidney cells transformed by a temperature-sensitive Rous sarcoma virus has been studied by polyacrylamide gel electrophoresis and autoradiography using cell monolayers prelabeled by lactoperoxidase-catalyzed radioiodination. Labeling of serum-starved cells under conditions that are nonpermissive for the expression of transformation reveals most of the radioactivity in the 250,000 molecular weight region. Parallel labeling of cells simultaneously exposed to serum limitation, under conditions that are permissive for the expression of transformation, reveals some radioactivity in the same slow-migrating region, but most of the label appears in the two faster migrating regions. The relative turnover of such external proteins has been investigated by examining the relative alterations in iodinated proteins after addition of normal levels of serum to a medium of serum-starved cells. There is a greater relative turnover of the high-molecular-weight external component under conditions in which ther transformation phenotype is expressed, as compared with conditions that limit the expression of transformation.", "contents": "Turnover of high-molecular-weight cell surface proteins during growth and expression of malignant transformation. The turnover of cell surface proteins in normal rat kidney cells transformed by a temperature-sensitive Rous sarcoma virus has been studied by polyacrylamide gel electrophoresis and autoradiography using cell monolayers prelabeled by lactoperoxidase-catalyzed radioiodination. Labeling of serum-starved cells under conditions that are nonpermissive for the expression of transformation reveals most of the radioactivity in the 250,000 molecular weight region. Parallel labeling of cells simultaneously exposed to serum limitation, under conditions that are permissive for the expression of transformation, reveals some radioactivity in the same slow-migrating region, but most of the label appears in the two faster migrating regions. The relative turnover of such external proteins has been investigated by examining the relative alterations in iodinated proteins after addition of normal levels of serum to a medium of serum-starved cells. There is a greater relative turnover of the high-molecular-weight external component under conditions in which ther transformation phenotype is expressed, as compared with conditions that limit the expression of transformation."} {"id": "PMID:167947", "title": "Clonal isolation of epithelial cells from mouse lung adenoma.", "content": "Clones of epithelial-like cells were established from urethan-induced mouse lung adenoma. Electron microscopy of one clone showed that the cells contained lamellar inclusion bodies similar in appearance to those seen in the adenoma precursor, the type II alveolar pneumocyte. The clones exhibited characteristics associated with both \"transformed\" and \"normal\" cells in culture; i.e., although aneuploid, the cells grew at a slower rate than most transformed cells, did not form colonies in soft agar and, after prolonged subculture, were not tumorigenic when transplanted s.c. into appropriate hosts. Hydrocortisone treatment of the cloned cells led to growth stimulation and the eventual acquisition of neoplastic potential. Epithelial tumors were produced more readily in athymic, nude mice than in antilymphocyte serum-treated A/He mice. The cells are producing a C-type RNA virus into the culture medium.", "contents": "Clonal isolation of epithelial cells from mouse lung adenoma. Clones of epithelial-like cells were established from urethan-induced mouse lung adenoma. Electron microscopy of one clone showed that the cells contained lamellar inclusion bodies similar in appearance to those seen in the adenoma precursor, the type II alveolar pneumocyte. The clones exhibited characteristics associated with both \"transformed\" and \"normal\" cells in culture; i.e., although aneuploid, the cells grew at a slower rate than most transformed cells, did not form colonies in soft agar and, after prolonged subculture, were not tumorigenic when transplanted s.c. into appropriate hosts. Hydrocortisone treatment of the cloned cells led to growth stimulation and the eventual acquisition of neoplastic potential. Epithelial tumors were produced more readily in athymic, nude mice than in antilymphocyte serum-treated A/He mice. The cells are producing a C-type RNA virus into the culture medium."} {"id": "PMID:167948", "title": "Rosetting of antibody-sensitized tumor cells with anti-immunoglobulin antibody-coated erythrocytes by a new method for detecting antigens on cells.", "content": "Tumor cells were treated with rabbit antibody to tumor-associated cell surface antigens and tested with erythrocytes coated with antibody specific for the sensitizing rabbit immunoglobulin. The sensitized tumor cells formed rosettes with the indicator cells. By this method, we confirmed that line 1 and line 10 hepatoma cells (from two tumors independently induced by diethylnitrosamine in strain 2 guinea pigs) bear antigens not present on normal liver cells. We also confirmed that line 1 and line 10 cells bear antigenically different tumor-associated cell surface antigens. This method appears simpler than other serological methods for detecting tumor-associated cell surface antigens on tumor cells. Also, this method may be a general one for detecting and enumerating cells bearing surface antigens.", "contents": "Rosetting of antibody-sensitized tumor cells with anti-immunoglobulin antibody-coated erythrocytes by a new method for detecting antigens on cells. Tumor cells were treated with rabbit antibody to tumor-associated cell surface antigens and tested with erythrocytes coated with antibody specific for the sensitizing rabbit immunoglobulin. The sensitized tumor cells formed rosettes with the indicator cells. By this method, we confirmed that line 1 and line 10 hepatoma cells (from two tumors independently induced by diethylnitrosamine in strain 2 guinea pigs) bear antigens not present on normal liver cells. We also confirmed that line 1 and line 10 cells bear antigenically different tumor-associated cell surface antigens. This method appears simpler than other serological methods for detecting tumor-associated cell surface antigens on tumor cells. Also, this method may be a general one for detecting and enumerating cells bearing surface antigens."} {"id": "PMID:167949", "title": "Morphological patterns of primary nonendocrine human pancreas carcinoma.", "content": "The study of histological sections of 406 cases of nonendocrine pancreas carcinoma at Memorial Hospital indicated that morphological patterns of pancreas carcinoma could be delineated as follows: duct cell adenocarcinoma (76%), giant-cell carcinoma (5%), microadenocarcinoma (4%), adenosquamous cancinoma (4%), mucinous adenocarcinoma (2%), anaplastic carcinoma (2%), cystadenocarcinoma (1%), acinar cell carcinoma (1%), carcinoma in childhood (under 1%), unclassified (7%). In 195 cases of patients with pancreas carcinoma, search was made for changes in the pancreas duct epithelium and these were compared to duct epithelium in a control group of 100 pancreases from autopsies of patients with nonpancreatic cancer. The following incidences were found for pancreas cancer and nonpancreatic cancer, respectively: mucous cell hypertrophy, 39 versus 28%; pyloric gland metaplasia, 28 and 17%; epidermoid metaplasia, 6 and 12%; papillary hyperplasia, 42 and 12%; atypical duct hyperplasia, 14% and none; cancinoma in situ in 19% and none in the control group. Mucin in the majority of pancreas cancers suggested that the cell type of origin of the common pancreas cancer is the mucin-producing duct epithelium. The association of atypias and carcinomas in situ in the patients with pancreas carcinoma implies, by analogy to other organs, that there may be a significant latent period between the appearance of carcinoma in situ and the grossly recognizable pancreas cancer.", "contents": "Morphological patterns of primary nonendocrine human pancreas carcinoma. The study of histological sections of 406 cases of nonendocrine pancreas carcinoma at Memorial Hospital indicated that morphological patterns of pancreas carcinoma could be delineated as follows: duct cell adenocarcinoma (76%), giant-cell carcinoma (5%), microadenocarcinoma (4%), adenosquamous cancinoma (4%), mucinous adenocarcinoma (2%), anaplastic carcinoma (2%), cystadenocarcinoma (1%), acinar cell carcinoma (1%), carcinoma in childhood (under 1%), unclassified (7%). In 195 cases of patients with pancreas carcinoma, search was made for changes in the pancreas duct epithelium and these were compared to duct epithelium in a control group of 100 pancreases from autopsies of patients with nonpancreatic cancer. The following incidences were found for pancreas cancer and nonpancreatic cancer, respectively: mucous cell hypertrophy, 39 versus 28%; pyloric gland metaplasia, 28 and 17%; epidermoid metaplasia, 6 and 12%; papillary hyperplasia, 42 and 12%; atypical duct hyperplasia, 14% and none; cancinoma in situ in 19% and none in the control group. Mucin in the majority of pancreas cancers suggested that the cell type of origin of the common pancreas cancer is the mucin-producing duct epithelium. The association of atypias and carcinomas in situ in the patients with pancreas carcinoma implies, by analogy to other organs, that there may be a significant latent period between the appearance of carcinoma in situ and the grossly recognizable pancreas cancer."} {"id": "PMID:167950", "title": "Acetoacetate coenzyme A transferase activity in rat hepatomas.", "content": "The presence of succinyl-coenzyme A:acetoacetate CoA transferase (CoA transferase) (EC 2.8.3.5), an initiator of ketone body utilization in nonhepatic tissue, was examined in liver from normal, partly hepatectomized, neonatal, and tumor-bearing rats, as well as in a series of transplantable rat hepatomas ranging widely in growth rate. While levels of CoA transferase are extremely low in normal, host, and regenerating liver, considerable amounts of activity are detectable in neonatal liver and in the hepatomas. In fact, the content of CoA transferase in the series of Morris hepatomas increases progressively with increase in tumor-growth rate. The fastest-growing tumor studied (7288Ctc) contains about the same amount of CoA transferase activity as rat skeletal muscle (i.e., an activity of about 0.1 mumole of acetoacetate used per min per g tissue). These results clearly indicate that the faster-growing hepatomas have adequate capacity to utilize ketone bodies in bioenergetic or biosynthetic activities. Furthermore, the enzymes from normal and hepatoma 7288Ctc tissues are quite similar with respect to (a) size of about 10(5) daltons, (b) reaction mechanism requiring formation of an enzyme:CoA intermediate (from ping-pong kinetic data), and (c) various kinetic parameters (such as Michaelis constants, product competitive inhibition constants, and acetoacetate substrate inhibition). The enzymes from rat skeletal muscle and Morris hepatoma 7288Ctc have the same isoelectric point (7.6), which differs from that for the rat heart enzyme (6.8).", "contents": "Acetoacetate coenzyme A transferase activity in rat hepatomas. The presence of succinyl-coenzyme A:acetoacetate CoA transferase (CoA transferase) (EC 2.8.3.5), an initiator of ketone body utilization in nonhepatic tissue, was examined in liver from normal, partly hepatectomized, neonatal, and tumor-bearing rats, as well as in a series of transplantable rat hepatomas ranging widely in growth rate. While levels of CoA transferase are extremely low in normal, host, and regenerating liver, considerable amounts of activity are detectable in neonatal liver and in the hepatomas. In fact, the content of CoA transferase in the series of Morris hepatomas increases progressively with increase in tumor-growth rate. The fastest-growing tumor studied (7288Ctc) contains about the same amount of CoA transferase activity as rat skeletal muscle (i.e., an activity of about 0.1 mumole of acetoacetate used per min per g tissue). These results clearly indicate that the faster-growing hepatomas have adequate capacity to utilize ketone bodies in bioenergetic or biosynthetic activities. Furthermore, the enzymes from normal and hepatoma 7288Ctc tissues are quite similar with respect to (a) size of about 10(5) daltons, (b) reaction mechanism requiring formation of an enzyme:CoA intermediate (from ping-pong kinetic data), and (c) various kinetic parameters (such as Michaelis constants, product competitive inhibition constants, and acetoacetate substrate inhibition). The enzymes from rat skeletal muscle and Morris hepatoma 7288Ctc have the same isoelectric point (7.6), which differs from that for the rat heart enzyme (6.8)."} {"id": "PMID:167951", "title": "Tumor-selective inhibition of the incorporation of 3H-labeled amino acids into protein by cyanate.", "content": "Sodium cyanate at a dose level of 125 or 250 mg/kg i.p. caused an inhibition of incorporation of 3H-labeled amino acids into cytoplasmic and nuclear proteins of the rapidly growing hepatoma 7777 and the slowly growing hepatoma 9618A. There was no inhibitory effect on 3H-labeled amino acid incorporation into protein in the livers of rats bearing these tumors. Studies on the effects of sodium cyanate on incorporation of 3H-labeled amino acids into total acid-insoluble material indicated that a greater than 85% inhibition could be achieved in hepatoma 5123C, hepatoma 9618A2, and the MK3 kidney tumor with either little or no effect in host liver, kidneys, brain, skeletal muscle, intestinal mucosa, and regenerating liver after partial hepatectomy.", "contents": "Tumor-selective inhibition of the incorporation of 3H-labeled amino acids into protein by cyanate. Sodium cyanate at a dose level of 125 or 250 mg/kg i.p. caused an inhibition of incorporation of 3H-labeled amino acids into cytoplasmic and nuclear proteins of the rapidly growing hepatoma 7777 and the slowly growing hepatoma 9618A. There was no inhibitory effect on 3H-labeled amino acid incorporation into protein in the livers of rats bearing these tumors. Studies on the effects of sodium cyanate on incorporation of 3H-labeled amino acids into total acid-insoluble material indicated that a greater than 85% inhibition could be achieved in hepatoma 5123C, hepatoma 9618A2, and the MK3 kidney tumor with either little or no effect in host liver, kidneys, brain, skeletal muscle, intestinal mucosa, and regenerating liver after partial hepatectomy."} {"id": "PMID:167952", "title": "Comparison of the cytidine 5'-diphosphate and adenosine 5'-diphosphate reductase activities of mammalian ribonucleotide reductase.", "content": "A comparison of the cytidine 5'-diphosphate (CDP) and adenosine 5'-diphosphate (ADP) reductase activities from Ehrlich tumor cells was made to determine if the properties of the enzyme for these substrates were the same, except for the allosteric effector. It was observed that various purification steps did not result in an enzyme fraction that had a constant ratio of CDP:ADP reductase activities. The optimal Mg2+ ion concentration for CDP reduction was 3 to 4 mM, while the optimal Mg2+ ion concentration for ADP reduction was 0.1 mM inhibited ADP reduction. CDP reduction was relatively insensitive to the presence of dimethylformamide or dimethyl sulfoxide in the reaction mixture, but ADP reduction was decreased in the presence of these two compounds. Periodate-oxidized adenosine 5'-monophosphate, on incubation with the enzyme, had a greater effect on CDP reduction but little or no effect on ADP reduction. The response of the CDP and ADP reductase activities to the same negative effector was essentially the same. Both CDP and ADP reductions showed similar decreases in the presence of various concentrations of deoxyadenosine 5'-triphosphate. These data suggest that the Ehrlich tumor cell reductase enzyme system could consist of at least two different enzymes that may be regulated by the same allosteric protein.", "contents": "Comparison of the cytidine 5'-diphosphate and adenosine 5'-diphosphate reductase activities of mammalian ribonucleotide reductase. A comparison of the cytidine 5'-diphosphate (CDP) and adenosine 5'-diphosphate (ADP) reductase activities from Ehrlich tumor cells was made to determine if the properties of the enzyme for these substrates were the same, except for the allosteric effector. It was observed that various purification steps did not result in an enzyme fraction that had a constant ratio of CDP:ADP reductase activities. The optimal Mg2+ ion concentration for CDP reduction was 3 to 4 mM, while the optimal Mg2+ ion concentration for ADP reduction was 0.1 mM inhibited ADP reduction. CDP reduction was relatively insensitive to the presence of dimethylformamide or dimethyl sulfoxide in the reaction mixture, but ADP reduction was decreased in the presence of these two compounds. Periodate-oxidized adenosine 5'-monophosphate, on incubation with the enzyme, had a greater effect on CDP reduction but little or no effect on ADP reduction. The response of the CDP and ADP reductase activities to the same negative effector was essentially the same. Both CDP and ADP reductions showed similar decreases in the presence of various concentrations of deoxyadenosine 5'-triphosphate. These data suggest that the Ehrlich tumor cell reductase enzyme system could consist of at least two different enzymes that may be regulated by the same allosteric protein."} {"id": "PMID:167953", "title": "Rat mammary gland atypia produced by iodine blockade with perchlorate.", "content": "Prior published work from our laboratory concluded that there was a need for appropriate metabolic activity of iodine in breast tissue for normal growth and development. Results from studies in rats that were made iodine deficient showed histological changes in the breasts that were atypical and dysplastic. These tissue findings were further affected by the presence of estrogen and thyroxine. These changes parallel the iodine uptake of the tissues, thus representing a difference in the utilization of iodine by the mammary glands. Using an ion blockade agent, sodium perchlorate, breast tissues lacking iodine were evaluated by both endocrine and histological techniques. A dose-response series was completed that showed that perchlorate therapy for 8 weeks at 400 mg/100 ml produced breast blockade by a reduction in iodine uptake of greater than 52% of the control. At these levels, the histological experimentation showed atypia and some pleomorphism of the cells, particularly in the glands of the lobules. Blockade was less effective in estrogen-treated groups. It is especially notable that both histological changes and uptake reduction were greatest in those breasts that had been rendered euthyroid by thyroxine replacement, thus clearly indicating the necessity of iodine itself for maintenance of normal breast development. By this blockade the responses of iodine inadequacy in the breast were shown to cause abnormal tissue changes relative to the percentage of the block obtained.", "contents": "Rat mammary gland atypia produced by iodine blockade with perchlorate. Prior published work from our laboratory concluded that there was a need for appropriate metabolic activity of iodine in breast tissue for normal growth and development. Results from studies in rats that were made iodine deficient showed histological changes in the breasts that were atypical and dysplastic. These tissue findings were further affected by the presence of estrogen and thyroxine. These changes parallel the iodine uptake of the tissues, thus representing a difference in the utilization of iodine by the mammary glands. Using an ion blockade agent, sodium perchlorate, breast tissues lacking iodine were evaluated by both endocrine and histological techniques. A dose-response series was completed that showed that perchlorate therapy for 8 weeks at 400 mg/100 ml produced breast blockade by a reduction in iodine uptake of greater than 52% of the control. At these levels, the histological experimentation showed atypia and some pleomorphism of the cells, particularly in the glands of the lobules. Blockade was less effective in estrogen-treated groups. It is especially notable that both histological changes and uptake reduction were greatest in those breasts that had been rendered euthyroid by thyroxine replacement, thus clearly indicating the necessity of iodine itself for maintenance of normal breast development. By this blockade the responses of iodine inadequacy in the breast were shown to cause abnormal tissue changes relative to the percentage of the block obtained."} {"id": "PMID:167954", "title": "Preferential inhibition by homopolyribonucleotides of the methylation of ribosomal ribonucleic acid and disruption of the production of ribosomes in a rat tumor.", "content": "The literature indicates that some mechanism other than the interferon or host-mediated immune enhancement might also be responsible for an antitumor effect of polyinosinate-polycytidylate [poly(I)-poly(C)]. We have examined the effect of this drug on the synthesis of ribosomes and other macromolecules in a rat tumor, the Novikoff ascites hepatoma. The nucleolus was one of the primary targets affected by the administration of poly(I)-poly(C) in vivo. A progressive decline of the activity of nucleolar ribosomal RNA methylases began within 2 hr, followed by a decline of the nucleolar RNA content. The activity of nucleolar RNA polymerase was inhibited only at later time intervals. Labeling of tumor macromolecules in vivo revealed that the methylation of ribosomal RNA and the production of ribosomes, particularly in the small subunits, were immediately and progressively affected, followed by inhibition of the synthesis of DNA, RNA, and protein at later times. In addition, poly(I)-poly(C) also induced disaggregation of polyribosomes and restricted the movements of nuclear RNA to cytoplasm and of cytoplasmic protein to nucleus. These in vivo effects of poly(I)-poly(C) on tumor cells was observed neither on the host livers nor on livers of normal rats. Studies on isolated nucleoli showed that the in vitro addition of polyinosinate and several other compounds actively inhibited tumor ribosomal RNA methylases but were devoid of inhibitory effect against liver ribosomal RNA methylases; these results augment other studies in the literature in suggesting a selective effect of the polyinosinate moiety on tumor cells. We conclude from this study that initial impairment of the methylation of ribosomal precursor RNA, following exposure of tumor cells to poly(I)-poly(C), is responsible for the destruction of ribosomes, preferentially the small subunits, during the maturation processes. Failure to provide new ribosomes thus triggers the events limiting the growth of tumor cells.", "contents": "Preferential inhibition by homopolyribonucleotides of the methylation of ribosomal ribonucleic acid and disruption of the production of ribosomes in a rat tumor. The literature indicates that some mechanism other than the interferon or host-mediated immune enhancement might also be responsible for an antitumor effect of polyinosinate-polycytidylate [poly(I)-poly(C)]. We have examined the effect of this drug on the synthesis of ribosomes and other macromolecules in a rat tumor, the Novikoff ascites hepatoma. The nucleolus was one of the primary targets affected by the administration of poly(I)-poly(C) in vivo. A progressive decline of the activity of nucleolar ribosomal RNA methylases began within 2 hr, followed by a decline of the nucleolar RNA content. The activity of nucleolar RNA polymerase was inhibited only at later time intervals. Labeling of tumor macromolecules in vivo revealed that the methylation of ribosomal RNA and the production of ribosomes, particularly in the small subunits, were immediately and progressively affected, followed by inhibition of the synthesis of DNA, RNA, and protein at later times. In addition, poly(I)-poly(C) also induced disaggregation of polyribosomes and restricted the movements of nuclear RNA to cytoplasm and of cytoplasmic protein to nucleus. These in vivo effects of poly(I)-poly(C) on tumor cells was observed neither on the host livers nor on livers of normal rats. Studies on isolated nucleoli showed that the in vitro addition of polyinosinate and several other compounds actively inhibited tumor ribosomal RNA methylases but were devoid of inhibitory effect against liver ribosomal RNA methylases; these results augment other studies in the literature in suggesting a selective effect of the polyinosinate moiety on tumor cells. We conclude from this study that initial impairment of the methylation of ribosomal precursor RNA, following exposure of tumor cells to poly(I)-poly(C), is responsible for the destruction of ribosomes, preferentially the small subunits, during the maturation processes. Failure to provide new ribosomes thus triggers the events limiting the growth of tumor cells."} {"id": "PMID:167955", "title": "Hormone dependence and estradiol receptors in the D series of mammary nodule outgrowth lines and tumors.", "content": "Preneoplastic mammary nodule outgrowth lines were examined for their ability to grow and produce tumors in ovariectomized BALB/c mice. In addition, these nodule outgrowth lines and tumors derived from them were investigated for cytoplasmic estrogen receptor proteins by qualitative and quantitative techniques. Early ovariectomy, performed within 4 weeks after transplantation, slightly delayed but did not permanently block the ability of three different nodule lines to completely fill the fat pad with nodule tissue. Ovariectomy performed later than 4 weeks after transplantation or adrenalectomy performed early or late had no effect on nodule growth. Neither early nor late ovariectomy or adrenalectomy had an effect on the maintenance of the nodule alveolar phenotype. Ovariectomy performed 3 weeks after transplantation had little effect on the tumor potential of the low oncogenic line D1 or the high oncogenic line D2. Samples of nodule outgrowths transplanted from ovariectomized mice responded to a chemical carcinogen in a similar manner, as did nodule outgrowths transplanted from control experiments. Thus, the altered hormonal environmenment in ovariectomized mice apparently did not select for subpopulations of nodule cells with altered tumorigenic potentials. The ovarian independence of the nodule lines and tumors derived from them was correlated with a very low level of cytoplasmic estrogen receptor. These results, along with other data, illustrate the nature of the independence on ovarian hormonal control for tumorigenesis in these mammary tumor virus-free nodule lines.", "contents": "Hormone dependence and estradiol receptors in the D series of mammary nodule outgrowth lines and tumors. Preneoplastic mammary nodule outgrowth lines were examined for their ability to grow and produce tumors in ovariectomized BALB/c mice. In addition, these nodule outgrowth lines and tumors derived from them were investigated for cytoplasmic estrogen receptor proteins by qualitative and quantitative techniques. Early ovariectomy, performed within 4 weeks after transplantation, slightly delayed but did not permanently block the ability of three different nodule lines to completely fill the fat pad with nodule tissue. Ovariectomy performed later than 4 weeks after transplantation or adrenalectomy performed early or late had no effect on nodule growth. Neither early nor late ovariectomy or adrenalectomy had an effect on the maintenance of the nodule alveolar phenotype. Ovariectomy performed 3 weeks after transplantation had little effect on the tumor potential of the low oncogenic line D1 or the high oncogenic line D2. Samples of nodule outgrowths transplanted from ovariectomized mice responded to a chemical carcinogen in a similar manner, as did nodule outgrowths transplanted from control experiments. Thus, the altered hormonal environmenment in ovariectomized mice apparently did not select for subpopulations of nodule cells with altered tumorigenic potentials. The ovarian independence of the nodule lines and tumors derived from them was correlated with a very low level of cytoplasmic estrogen receptor. These results, along with other data, illustrate the nature of the independence on ovarian hormonal control for tumorigenesis in these mammary tumor virus-free nodule lines."} {"id": "PMID:167956", "title": "5'-nucleotide phosphodiesterase isoenzyme in patients with hepatitis B infection.", "content": "The hypothesis that hepatitis B infection is etiologically related to hepatoma has been investigated by studying the interrelationships between hepatitis B surface antigen (HBsAg, Australia antigen) and the fast-moving 5'-nucleotide phosphodiesterase Band V isoenzyme (5'-NPDase-V). Sera from 58 patients with viral hepatitis were tested for 5'-NPDase-V and HBsAg. The isoenzyme was found in 34 of 37 patients who were also positive for HBsAg but in only 4 of 21 hepatitis patients who were HBsAg negative. Five patients convalescing from hepatitis were negative for both HBsAg and the isoenzyme. Preparative gel electrophoresis showed that these 2 markers were different proteins. Of 34 hepatoma patients, 29 were positive for 5'-NPDase-V. Only 1 isoenzyme-positive patient was positive for HBsAg by counterimmunoelectrophoresis. However, of 16 isoenzyme-positive hepatoma patients available for radioimmunoassay, 8 were NBsAg positive (50%). None of 21 hepatoma samples tested for antibody to NBsAg was positive. Of 21 \"normal\" carriers of HBsAg and 10 carriers with Down's syndrome, 4 persons were detected with the isoenzyme. The results suggest that HBsAg and 5'-NPDase-V in the presence of liver damage are associated and thus provide a new marker enzyme between hepatitis B infection and hepatoma.", "contents": "5'-nucleotide phosphodiesterase isoenzyme in patients with hepatitis B infection. The hypothesis that hepatitis B infection is etiologically related to hepatoma has been investigated by studying the interrelationships between hepatitis B surface antigen (HBsAg, Australia antigen) and the fast-moving 5'-nucleotide phosphodiesterase Band V isoenzyme (5'-NPDase-V). Sera from 58 patients with viral hepatitis were tested for 5'-NPDase-V and HBsAg. The isoenzyme was found in 34 of 37 patients who were also positive for HBsAg but in only 4 of 21 hepatitis patients who were HBsAg negative. Five patients convalescing from hepatitis were negative for both HBsAg and the isoenzyme. Preparative gel electrophoresis showed that these 2 markers were different proteins. Of 34 hepatoma patients, 29 were positive for 5'-NPDase-V. Only 1 isoenzyme-positive patient was positive for HBsAg by counterimmunoelectrophoresis. However, of 16 isoenzyme-positive hepatoma patients available for radioimmunoassay, 8 were NBsAg positive (50%). None of 21 hepatoma samples tested for antibody to NBsAg was positive. Of 21 \"normal\" carriers of HBsAg and 10 carriers with Down's syndrome, 4 persons were detected with the isoenzyme. The results suggest that HBsAg and 5'-NPDase-V in the presence of liver damage are associated and thus provide a new marker enzyme between hepatitis B infection and hepatoma."} {"id": "PMID:167957", "title": "Properties of acidic saccharides produced by B16 melanoma cells treated with 1-methyl-3-isobutylxanthine.", "content": "A cyclic nucleotide phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine, promoted the differentiation and maturation of B16 melanoma cells, phenomena associated with biological alterations in the surface properties of the cells. 1-Methyl-3-isobutylxanthien inhibited cell replication and increased the intracellular content of melanin and cyclic adenosine 3':5'-monophosphate. Significantly greater amounts of sialoglycoproteins were associated with 1-methyl-3-isobutylxanthine-treated cells. However, the total amount of [3H] glucosamine incorporated into anionic polysaccharide (both sialoglycopeptide and mucopolysaccharides) was not significantly changed.", "contents": "Properties of acidic saccharides produced by B16 melanoma cells treated with 1-methyl-3-isobutylxanthine. A cyclic nucleotide phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine, promoted the differentiation and maturation of B16 melanoma cells, phenomena associated with biological alterations in the surface properties of the cells. 1-Methyl-3-isobutylxanthien inhibited cell replication and increased the intracellular content of melanin and cyclic adenosine 3':5'-monophosphate. Significantly greater amounts of sialoglycoproteins were associated with 1-methyl-3-isobutylxanthine-treated cells. However, the total amount of [3H] glucosamine incorporated into anionic polysaccharide (both sialoglycopeptide and mucopolysaccharides) was not significantly changed."} {"id": "PMID:167958", "title": "Comparison of physical and immunological properties of plasma membranes of two mouse leukemia cell lines, P388 and L1210.", "content": "A method for the isolation of the plasma membranes of the mouse leukemic cell P388 is described. The method includes surface labeling of the cell membrane with 125I. The 125I specific activity of the plasma membrane preparation is 10- to 13-fold higher than that of the cell homogenate; enzyme assays and electron microscopy further corroborate the purity of the P388 plasma membrane preparation. The predominant iodinated membrane proteins have molecular weights of 85,000, 66,000, and 13,000 daltons. Antibodies prepared against P388 and L1210 plasma membranes inhibit the growth of the corresponding cells in the absence of complement. They show cross-reactivity to each other but do not affect the growth of HeLa cells.", "contents": "Comparison of physical and immunological properties of plasma membranes of two mouse leukemia cell lines, P388 and L1210. A method for the isolation of the plasma membranes of the mouse leukemic cell P388 is described. The method includes surface labeling of the cell membrane with 125I. The 125I specific activity of the plasma membrane preparation is 10- to 13-fold higher than that of the cell homogenate; enzyme assays and electron microscopy further corroborate the purity of the P388 plasma membrane preparation. The predominant iodinated membrane proteins have molecular weights of 85,000, 66,000, and 13,000 daltons. Antibodies prepared against P388 and L1210 plasma membranes inhibit the growth of the corresponding cells in the absence of complement. They show cross-reactivity to each other but do not affect the growth of HeLa cells."} {"id": "PMID:167959", "title": "Changes in lymphoid cyclic adenosine 3':5'-monophosphate metabolism during murine leukemogenesis.", "content": "Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were slightly increased in preleukemic AKR mouse thymus cells, compared with nonleukemic thymus cells, but were markedly reduced in leukemic cells. Adenylate cyclase activity rose during the preleukemic and leukemic phases of leukemogenesis. Although the drop of epinephrine-induced stimulation of thymus adenylate cyclase in the preleukemic phase was probably age related, there was an additional decrease of adenylate cyclase activation by epinephrine in leukemic cells. Cyclic AMP phosphodiesterase activity was slightly higher in preleukemic cells and more than fourfold AKR thymus. These observations suggest that cyclic AMP phosphodiesterase is largely responsible for the low levels of cyclic AMP in leukemic cells. Significant changes in cyclic AMP metabolism are already detectable before neoplastic cells may be found in the thymus.", "contents": "Changes in lymphoid cyclic adenosine 3':5'-monophosphate metabolism during murine leukemogenesis. Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were slightly increased in preleukemic AKR mouse thymus cells, compared with nonleukemic thymus cells, but were markedly reduced in leukemic cells. Adenylate cyclase activity rose during the preleukemic and leukemic phases of leukemogenesis. Although the drop of epinephrine-induced stimulation of thymus adenylate cyclase in the preleukemic phase was probably age related, there was an additional decrease of adenylate cyclase activation by epinephrine in leukemic cells. Cyclic AMP phosphodiesterase activity was slightly higher in preleukemic cells and more than fourfold AKR thymus. These observations suggest that cyclic AMP phosphodiesterase is largely responsible for the low levels of cyclic AMP in leukemic cells. Significant changes in cyclic AMP metabolism are already detectable before neoplastic cells may be found in the thymus."} {"id": "PMID:167960", "title": "Sarcoma-negative leukemia-positive transformed cell culture established from a murine sarcoma virus-induced rat bone tumor.", "content": "Inoculation of the Soehner-Dmochowski isolate of the Moloney strain of murine sarcoma virus (MSV), designated MSV-SD, consistently leads to the development of bone tumors in the susceptible New Zealand black (NB) rats. Two separate cell cultures have been established from 2 individual MSV-SD-induced NB rat bone tumors. Cells of 1 bone tumor culture, designated RBT-E, are in early in vitro passages. These cells form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at a greatly enhanced rate, 5 times that of normal nontransformed rat embryo cells. Cells of the RBT-E culture release both MSV and murine leukemia virus (MuLV) and therefore contain sarcoma-positive leukemia-positive transformed cells. The other rat bone tumor culture, designated RBT-L, produced MSV at early passages. RBT-L culture has been passaged over 130 times in vitro. Cells of the RBT-L culture form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at an enhanced rate (3 times that of rat embryo cells), indicating the presence of transformed cells within the RBT-L culture. However, cells of the RBT-L culture at late passages (Passage 130 or more) produce only MuLV and no detectable MSV activity (as shown by the lack of tumor-inducing activity and the lack of focus-forming activities by direct assay or by infectious center assay). Attempts to rescue MSV activity from RBT-L cells by cocultivation with MuLV-producing mouse cells were not successful. The MuLV found in the RBT-L cells, however, is a competent helper virus capable of rescuing the MSV genome from MSV-SD-induced hamster bone tumor cells. All the available evidence supports the notion that late passages of the RBT-L culture contain transformed cells that do not produce conventionally detectable MSV. These cells are referred to as sarcoma-negative leukemia-positive cells. The sarcoma-negative leukemia-positive cells represent a different kind of MSV-induced transformed cells and provide a unique system for studies in search of MSV markers such as MSV-specific antigens and MSV-specific nucleotide sequences.", "contents": "Sarcoma-negative leukemia-positive transformed cell culture established from a murine sarcoma virus-induced rat bone tumor. Inoculation of the Soehner-Dmochowski isolate of the Moloney strain of murine sarcoma virus (MSV), designated MSV-SD, consistently leads to the development of bone tumors in the susceptible New Zealand black (NB) rats. Two separate cell cultures have been established from 2 individual MSV-SD-induced NB rat bone tumors. Cells of 1 bone tumor culture, designated RBT-E, are in early in vitro passages. These cells form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at a greatly enhanced rate, 5 times that of normal nontransformed rat embryo cells. Cells of the RBT-E culture release both MSV and murine leukemia virus (MuLV) and therefore contain sarcoma-positive leukemia-positive transformed cells. The other rat bone tumor culture, designated RBT-L, produced MSV at early passages. RBT-L culture has been passaged over 130 times in vitro. Cells of the RBT-L culture form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at an enhanced rate (3 times that of rat embryo cells), indicating the presence of transformed cells within the RBT-L culture. However, cells of the RBT-L culture at late passages (Passage 130 or more) produce only MuLV and no detectable MSV activity (as shown by the lack of tumor-inducing activity and the lack of focus-forming activities by direct assay or by infectious center assay). Attempts to rescue MSV activity from RBT-L cells by cocultivation with MuLV-producing mouse cells were not successful. The MuLV found in the RBT-L cells, however, is a competent helper virus capable of rescuing the MSV genome from MSV-SD-induced hamster bone tumor cells. All the available evidence supports the notion that late passages of the RBT-L culture contain transformed cells that do not produce conventionally detectable MSV. These cells are referred to as sarcoma-negative leukemia-positive cells. The sarcoma-negative leukemia-positive cells represent a different kind of MSV-induced transformed cells and provide a unique system for studies in search of MSV markers such as MSV-specific antigens and MSV-specific nucleotide sequences."} {"id": "PMID:167961", "title": "Morphological differentiation of cultured mouse glioblastoma cells induced by dibutyryl cyclic adenosine monophosphate.", "content": "A culture line of mouse glioblastoma cells changed morphologically to differentiated astrocyte-like cells when cultured in medium with dibutyryl cyclic adenosine monophosphate and theophylline. Morphological alteration occurred within only 5 hr when 3 mM dibutyryl cyclic adenosine monophosphate and 1 mM theophylline were used, and in 1 day when 1 mM theophylline were used. Cells showing this morphological change reverted completely to immature cells when they were transferred to medium without these two chemicals. Addition of 1 or 3 mM dibutyryl cyclic guanosine monophosphate with 1 mM theophylline to the medium also induced development of cytoplasmic processes from these cells and the cells became stellate, although the cytoplasmic processes were not as long or as numerous as those induced by dibutyryl cyclic adenosine monophosphate, and the altered cells could not be referred to as differentiated glia cells. Sodium butyrate induced morphological alterations similar to those induced by dibutyryl cyclic guanosine monophosphate, but fewer cells showed these alterations. Addition of cyclic adenosine monophosphate or cyclic guanosine monophosphate in the presence of theophylline or addition of theophylline alone did not induce morphological changes of the cells.", "contents": "Morphological differentiation of cultured mouse glioblastoma cells induced by dibutyryl cyclic adenosine monophosphate. A culture line of mouse glioblastoma cells changed morphologically to differentiated astrocyte-like cells when cultured in medium with dibutyryl cyclic adenosine monophosphate and theophylline. Morphological alteration occurred within only 5 hr when 3 mM dibutyryl cyclic adenosine monophosphate and 1 mM theophylline were used, and in 1 day when 1 mM theophylline were used. Cells showing this morphological change reverted completely to immature cells when they were transferred to medium without these two chemicals. Addition of 1 or 3 mM dibutyryl cyclic guanosine monophosphate with 1 mM theophylline to the medium also induced development of cytoplasmic processes from these cells and the cells became stellate, although the cytoplasmic processes were not as long or as numerous as those induced by dibutyryl cyclic adenosine monophosphate, and the altered cells could not be referred to as differentiated glia cells. Sodium butyrate induced morphological alterations similar to those induced by dibutyryl cyclic guanosine monophosphate, but fewer cells showed these alterations. Addition of cyclic adenosine monophosphate or cyclic guanosine monophosphate in the presence of theophylline or addition of theophylline alone did not induce morphological changes of the cells."} {"id": "PMID:167962", "title": "Cyclic adenosine 3':5'-monophosphate levels and activities of related enzymes in normal and leukemic lymphocytes.", "content": "The role of cyclic adenosine 3':5'-monophosphate (cyclic 3':5'-AMP) in the regulation of cell division in lymphocytes obtained from healthy donors and from patients with chronic lymphocytic leukemia (CLL) was investigated by determining the levels of cyclic 3':5'-AMP and glycogen and also the activities of several enzymes that are closely associated with the metabolism of these cellular components. Intracellular levels of cyclic 3':5'-AMP were measured in normal and CLL lymphocytes in nondividing, dividing, and quiescent [after phytohemagglutinin (PHA) addition]states. In normal lymphocytes the levels of cyclic 3':5'-AMP fluctuated throughout the cell cycle after PHA addition, whereas in CLL lymphocytes the levels were approximately 3-fold lower than in normal cells and remained relatively constant before, during, and after mitogenic stimulation. Normal cells contained approximately 3-fold lower levels of glycogen than CLL cells, whereas glycogen phosphorylase activities were increased 2- to 4-fold above those in nondividing cells in normal but not in CLL lymphocytes after stimulation with PHA. Furthermore, cyclic 3':5'-AMP phosphodiesterase activities were higher in CLL lymphocytes than in normal ones. Collectively, these studies demonstrated that (a) the intracellular levels of cyclic 3':5'-AMP differ in these two cell types; (b) the levels of cyclic 3':5'-AMP and glycogen qualitatively correlate with the activities of the enzymes that are related to these components; and (c) an inverse relationship between the levels of cyclic 3':5'-AMP and cell growth exists in mitogen-stimulated lymphocytes from healthy donors but not from patients with CLL. These biochemical differences are presumed to exist between normal and \"leukemic\" lymphocytes, but alternatively they may reflect normal populations of immunologically distinct lymphocytes.", "contents": "Cyclic adenosine 3':5'-monophosphate levels and activities of related enzymes in normal and leukemic lymphocytes. The role of cyclic adenosine 3':5'-monophosphate (cyclic 3':5'-AMP) in the regulation of cell division in lymphocytes obtained from healthy donors and from patients with chronic lymphocytic leukemia (CLL) was investigated by determining the levels of cyclic 3':5'-AMP and glycogen and also the activities of several enzymes that are closely associated with the metabolism of these cellular components. Intracellular levels of cyclic 3':5'-AMP were measured in normal and CLL lymphocytes in nondividing, dividing, and quiescent [after phytohemagglutinin (PHA) addition]states. In normal lymphocytes the levels of cyclic 3':5'-AMP fluctuated throughout the cell cycle after PHA addition, whereas in CLL lymphocytes the levels were approximately 3-fold lower than in normal cells and remained relatively constant before, during, and after mitogenic stimulation. Normal cells contained approximately 3-fold lower levels of glycogen than CLL cells, whereas glycogen phosphorylase activities were increased 2- to 4-fold above those in nondividing cells in normal but not in CLL lymphocytes after stimulation with PHA. Furthermore, cyclic 3':5'-AMP phosphodiesterase activities were higher in CLL lymphocytes than in normal ones. Collectively, these studies demonstrated that (a) the intracellular levels of cyclic 3':5'-AMP differ in these two cell types; (b) the levels of cyclic 3':5'-AMP and glycogen qualitatively correlate with the activities of the enzymes that are related to these components; and (c) an inverse relationship between the levels of cyclic 3':5'-AMP and cell growth exists in mitogen-stimulated lymphocytes from healthy donors but not from patients with CLL. These biochemical differences are presumed to exist between normal and \"leukemic\" lymphocytes, but alternatively they may reflect normal populations of immunologically distinct lymphocytes."} {"id": "PMID:167963", "title": "Production of a serine-protease with macrophage migration-inhibitory factor activity by virus-transformed cells and human tumor cell lines.", "content": "BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed.", "contents": "Production of a serine-protease with macrophage migration-inhibitory factor activity by virus-transformed cells and human tumor cell lines. BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed."} {"id": "PMID:167964", "title": "The distribution and properties of aspartyl transfer RNA in human and animal tumors.", "content": "The elution profile of aspartyl transfer RNA (aspartyl-tRNA) from reversed phase 5 chromatography for tRNA from a spectrum of animal tissues and tumors and human tumors has been examined. It was found that SV40-induced hamster tumors, BHK21/cl 13 cells in culture, certain carcinogen-induced tumors in the Ehrlich ascites tumor, and a number of human carcinomas and adenocarcinomas contained a distinct increase (3- to 20-fold) in the percentage of a late-eluting aspartyl-tRNA over that found in nonmalignant tissues, other animal tumors, and in human melanomas and sarcomas. The ability of the late-eluting aspartyl-tRNAAspIV to bind to ribosomes in the presence of the codons for aspartic acid was compared to that of aspartyl-tRNAAspIII and was found to be approximately the same. Also, the ability of each of the 4 isoaccepting species of aspartyl-tRNA to engage in ribosomal incorporation of aspartic acid into a polypeptide was determined. All 4 isoacceptors function equally well in the amino acid incorporation.", "contents": "The distribution and properties of aspartyl transfer RNA in human and animal tumors. The elution profile of aspartyl transfer RNA (aspartyl-tRNA) from reversed phase 5 chromatography for tRNA from a spectrum of animal tissues and tumors and human tumors has been examined. It was found that SV40-induced hamster tumors, BHK21/cl 13 cells in culture, certain carcinogen-induced tumors in the Ehrlich ascites tumor, and a number of human carcinomas and adenocarcinomas contained a distinct increase (3- to 20-fold) in the percentage of a late-eluting aspartyl-tRNA over that found in nonmalignant tissues, other animal tumors, and in human melanomas and sarcomas. The ability of the late-eluting aspartyl-tRNAAspIV to bind to ribosomes in the presence of the codons for aspartic acid was compared to that of aspartyl-tRNAAspIII and was found to be approximately the same. Also, the ability of each of the 4 isoaccepting species of aspartyl-tRNA to engage in ribosomal incorporation of aspartic acid into a polypeptide was determined. All 4 isoacceptors function equally well in the amino acid incorporation."} {"id": "PMID:167965", "title": "Human neuroblastoma in nude mice.", "content": "For establishment of a reproducible model of human neuroblastoma, 2 to 5 million of established neuroblastoma cell lines (SK-N-SH, SK-N-MC) were injected s.c. or i.p. into 20 nu/nu mice of a predominantly Swiss back-ground. Following latency periods of 8 to 21 days, tumors developed at the injection site and grew to 4-ml volumes within 3 weeks. Histologically, the tumors resembled the original metastases from which the tumors were derived; however, the SK-N-SH appeared to have evidence of morphological differentiation. When compared to monolayer culture, the heterotransplanted SK-N-SH tumor had decreased dopamine-beta-hydroxylase activity and elevated cyclic adenosine 3':5'-monophosphate phosphodiesterase activity. Activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the transplanted SK-N-MC tumor was not appreciably different from the activity in the cultured cells. Serum dopamine-beta-hydroxylase levels in the mice bearing SK-N-SH tumor increased threefold. The SK-N-MC cultured cells lacked dopamine-beta-hydroxylase and did not alter existing serum levels in the SK-N-MC tumor-bearing mice. 67Ga injected i.v. was found to localize in the tumor after 24 hr. Human neuroblastoma in the nude mouse can be a reproducible and informative model for tumor pharmacology, screening, radionuclides, tumor localization and imaging, and investigating morphological differentiation.", "contents": "Human neuroblastoma in nude mice. For establishment of a reproducible model of human neuroblastoma, 2 to 5 million of established neuroblastoma cell lines (SK-N-SH, SK-N-MC) were injected s.c. or i.p. into 20 nu/nu mice of a predominantly Swiss back-ground. Following latency periods of 8 to 21 days, tumors developed at the injection site and grew to 4-ml volumes within 3 weeks. Histologically, the tumors resembled the original metastases from which the tumors were derived; however, the SK-N-SH appeared to have evidence of morphological differentiation. When compared to monolayer culture, the heterotransplanted SK-N-SH tumor had decreased dopamine-beta-hydroxylase activity and elevated cyclic adenosine 3':5'-monophosphate phosphodiesterase activity. Activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the transplanted SK-N-MC tumor was not appreciably different from the activity in the cultured cells. Serum dopamine-beta-hydroxylase levels in the mice bearing SK-N-SH tumor increased threefold. The SK-N-MC cultured cells lacked dopamine-beta-hydroxylase and did not alter existing serum levels in the SK-N-MC tumor-bearing mice. 67Ga injected i.v. was found to localize in the tumor after 24 hr. Human neuroblastoma in the nude mouse can be a reproducible and informative model for tumor pharmacology, screening, radionuclides, tumor localization and imaging, and investigating morphological differentiation."} {"id": "PMID:167966", "title": "Evaluation of the cell-mediated immune response to murine sarcoma virus by (125I)iododeoxyuridine assay and comparison with chromium 51 and microcytotoxicity assays.", "content": "The cell-mediated immune response of C57BL/6 mice to murine sarcoma virus (MSV) was examined by the [125I]-iododeoxyuridine release cytotoxicity assay using MSV-induced sarcoma tissue culture cell lines as target cells. Cellular cytotoxicity was detected as early as 3 days after virus inoculation. Most mice assayed between 12 and 17 days after MSV inoculation gave positive results with maximum levels of activity present on Days 13 and 14. Reactivity was frequently detected for up to 100 days after MSV inoculation, although at low levels (5 to 10%). Additional experiments comparing the kinetics of the cellular response as measured by different in vitro cytotoxicity assays were performed. The results showed a good direct correlation between the [125I]iododeoxyuridine release assay and a 51Cr release assay. A similar pattern of reactivity was also observed when the cellular response was measured by a visual microcytotoxicity assay, although reactivity dropped off more rapidly and became undetectable in most instances by 20 days after injection of MSV. Studies on effector cell type revealed that cytotoxicity in all three assays was T-cell dependent, being eliminated by treatment with anti-theta plus complement. Macrophages did not appear to play a role, since treatment with carbonyl iron and magnet had no effect.", "contents": "Evaluation of the cell-mediated immune response to murine sarcoma virus by (125I)iododeoxyuridine assay and comparison with chromium 51 and microcytotoxicity assays. The cell-mediated immune response of C57BL/6 mice to murine sarcoma virus (MSV) was examined by the [125I]-iododeoxyuridine release cytotoxicity assay using MSV-induced sarcoma tissue culture cell lines as target cells. Cellular cytotoxicity was detected as early as 3 days after virus inoculation. Most mice assayed between 12 and 17 days after MSV inoculation gave positive results with maximum levels of activity present on Days 13 and 14. Reactivity was frequently detected for up to 100 days after MSV inoculation, although at low levels (5 to 10%). Additional experiments comparing the kinetics of the cellular response as measured by different in vitro cytotoxicity assays were performed. The results showed a good direct correlation between the [125I]iododeoxyuridine release assay and a 51Cr release assay. A similar pattern of reactivity was also observed when the cellular response was measured by a visual microcytotoxicity assay, although reactivity dropped off more rapidly and became undetectable in most instances by 20 days after injection of MSV. Studies on effector cell type revealed that cytotoxicity in all three assays was T-cell dependent, being eliminated by treatment with anti-theta plus complement. Macrophages did not appear to play a role, since treatment with carbonyl iron and magnet had no effect."} {"id": "PMID:167967", "title": "Organized inclusions in astrocytic and amorphous inclusions in neuronal mitochondria of human frontal brain tissue.", "content": "Brain tissue specimens were obtained early post mortem from the frontal lobe of seven unselected elderly subjects known to have been free of neurologic disease. Electron microscopically, two types of intramitochondrial inclusions were seen in four of seven cases. In two cases a few astrocyte mitochondria of the gyral white matter showed dense, elongated inclusions with an ordered linear substructure. These inclusions were, as a rule, accompanied by a row of prismatic cristae. In three cases some nerve cell mitochondria contained amorphous material of medium density and compact appearance. The globular masses often occupied the whole width of the mitochondrion. A relationship between the observed finding and a particular disease or morbid condition was not apparent. The inclusions are regarded as the morphologic substrate of a nonspecific metabolic change or degenerative process of the mitochondrion.", "contents": "Organized inclusions in astrocytic and amorphous inclusions in neuronal mitochondria of human frontal brain tissue. Brain tissue specimens were obtained early post mortem from the frontal lobe of seven unselected elderly subjects known to have been free of neurologic disease. Electron microscopically, two types of intramitochondrial inclusions were seen in four of seven cases. In two cases a few astrocyte mitochondria of the gyral white matter showed dense, elongated inclusions with an ordered linear substructure. These inclusions were, as a rule, accompanied by a row of prismatic cristae. In three cases some nerve cell mitochondria contained amorphous material of medium density and compact appearance. The globular masses often occupied the whole width of the mitochondrion. A relationship between the observed finding and a particular disease or morbid condition was not apparent. The inclusions are regarded as the morphologic substrate of a nonspecific metabolic change or degenerative process of the mitochondrion."} {"id": "PMID:167968", "title": "Annulate lamellae and crystalline inclusions in granular endoplasmic reticulum of the islet organ and associated tissues of a cyclostome, Myxine glutinosa.", "content": "Cytoplasmic annylate lamellae were found in the islet organ of a cyclostome, the hagfish (Myxine glutinosa), predominantly in cells interpreted as young proliferating beta-cells, and also in endocrine cells and enterocytes of the bile duct and gut and in the endothelial cells of small blood vessels. A close association was observed annulate lamellae and granular endoplasmic reticulum. Both in cells with and in those without annulate lamellae, crystalline inclusions of proteinaceous nature were seen in granular endoplasmic reticulum. These inclusions were occasionally closely associated to annulate lamellae, and a direct continuity could be seen between granular endoplasmic reticulum and the outer nuclear membrane surrounding an inclusion partially situated in the perinuclear cisterna. Rod-shaped structures and rounded electron dense bodies were seen in the nuclei of some islet parenchymal cells. The presence of annulate lamellae in the islet organ and associated tissues of Myxine glutinosa is believed to be related to the very high phylogenetic age of this species. The close association observed between annulate lamellae, granular endoplasmic reticulum, crystalline inclusions, and sometimes also nuclear membranes, may be of functional significance.", "contents": "Annulate lamellae and crystalline inclusions in granular endoplasmic reticulum of the islet organ and associated tissues of a cyclostome, Myxine glutinosa. Cytoplasmic annylate lamellae were found in the islet organ of a cyclostome, the hagfish (Myxine glutinosa), predominantly in cells interpreted as young proliferating beta-cells, and also in endocrine cells and enterocytes of the bile duct and gut and in the endothelial cells of small blood vessels. A close association was observed annulate lamellae and granular endoplasmic reticulum. Both in cells with and in those without annulate lamellae, crystalline inclusions of proteinaceous nature were seen in granular endoplasmic reticulum. These inclusions were occasionally closely associated to annulate lamellae, and a direct continuity could be seen between granular endoplasmic reticulum and the outer nuclear membrane surrounding an inclusion partially situated in the perinuclear cisterna. Rod-shaped structures and rounded electron dense bodies were seen in the nuclei of some islet parenchymal cells. The presence of annulate lamellae in the islet organ and associated tissues of Myxine glutinosa is believed to be related to the very high phylogenetic age of this species. The close association observed between annulate lamellae, granular endoplasmic reticulum, crystalline inclusions, and sometimes also nuclear membranes, may be of functional significance."} {"id": "PMID:167969", "title": "Characterization by different techniques of adrenocorticotropin and gonadotropin producing cells in lerot pituitary (Eliomys quercinus).", "content": "Adrenocorticotropin and gonadotropin producing cells were localized in the adenohypothysis of normal Lerots by using anti-beta 1-24 ACTH, anti-LH, anti-LH beta, anti-PMSG antisera. In order to study their fine structure two techniques were employed: a superimposition technique which consists of detailed comparisons between the same cells in light, fluorescence and electron microscopic preparations and an immunocytochemical technique on ultra-thin sections using the peroxidase anti-peroxidase complex technique. The superimposistion technique allows an excellent description of cell ultrastructure of individually identified cells of each type. With this method we were able to describe the corticotropin secreting cells as lucent cells with electron dense granules ranging in size from 2500 to 3500 A. The gonodotropin secreting cells are darker and their granules are about 2000 A in diameter.", "contents": "Characterization by different techniques of adrenocorticotropin and gonadotropin producing cells in lerot pituitary (Eliomys quercinus). Adrenocorticotropin and gonadotropin producing cells were localized in the adenohypothysis of normal Lerots by using anti-beta 1-24 ACTH, anti-LH, anti-LH beta, anti-PMSG antisera. In order to study their fine structure two techniques were employed: a superimposition technique which consists of detailed comparisons between the same cells in light, fluorescence and electron microscopic preparations and an immunocytochemical technique on ultra-thin sections using the peroxidase anti-peroxidase complex technique. The superimposistion technique allows an excellent description of cell ultrastructure of individually identified cells of each type. With this method we were able to describe the corticotropin secreting cells as lucent cells with electron dense granules ranging in size from 2500 to 3500 A. The gonodotropin secreting cells are darker and their granules are about 2000 A in diameter."} {"id": "PMID:167970", "title": "Light- and electron-microscopic studies on the secretory cytology of the adenohypophysis of the Japanese quail, Coturnix coturnix japonica.", "content": "The effects of thyroidectomy, adrenalectomy, and castration on the pars distalis of male Japanese quail, and of injection of LH-RH on sexually inactive females, were investigated by light and electron microscopy. Correlation between light and electron microscopy was attained by use of alternate thin and thick sections. Six types of secretory cells were identified and the ultrastructural characteristics described. Putative endocrine functions have been designated on the basis of responses to experimental interventions and on other criteria. The putative STH cells are characterized by the presence of large dense secretory granules (250-300 nm) that are stained with orange-G by the trichrome method. They occur only in the caudal lobe and appear to be unchanged by castration, thyroidectomy, adrenalectomy and LH-RH injection. The putative prolactin cells are characterized by large (400-600 nm), spherical or polmorphic, dense secretory granules stainable with acid fuchsin and aniline blue; prominent Golgi apparatus and well developed endoplasmic reticulum with densely packed, regularly parallel lamellae. They are found mainly in the cephalic lobe. The prolactin cells develop some vacuolization after adrenalectomy and undergo some degeneration after castration. The ACTH cells, which are restricted to the cephalic lobe, are identified by the dense, spherical granules (250-300 nm) that are stained with acid fuchsin. After adrenalectomy, they lose their secretory granules and are transformed into large, chromophobic adrenalectomy cells. TSH cells are so designated by their response to thyroidectomy including loss of their fine secretory granules and transformation to large, vacuolated thyroidectomy cells. We have found TSH cells and thyroidectomy cells only in the cephalic lobe. Basophilic cells, considered to be gonadotropes, occur in both the cephalic and caudal lobes. The gonadotropes of the cephalic lobe appear to have slightly larger (120-200 nm) granules than the caudal lobe (120-150 nm). However, after castration, the gonadotropes in both lobes become hypertrophied and vacuolated and are transformed into mutually indistinguishable castration cells. Twenty minutes after injection with LH-RH, the gonadotropes of both lobes increase in size and number, degranulate, develop vacuoles in the cytoplasm, and appear very similar to castration cells.", "contents": "Light- and electron-microscopic studies on the secretory cytology of the adenohypophysis of the Japanese quail, Coturnix coturnix japonica. The effects of thyroidectomy, adrenalectomy, and castration on the pars distalis of male Japanese quail, and of injection of LH-RH on sexually inactive females, were investigated by light and electron microscopy. Correlation between light and electron microscopy was attained by use of alternate thin and thick sections. Six types of secretory cells were identified and the ultrastructural characteristics described. Putative endocrine functions have been designated on the basis of responses to experimental interventions and on other criteria. The putative STH cells are characterized by the presence of large dense secretory granules (250-300 nm) that are stained with orange-G by the trichrome method. They occur only in the caudal lobe and appear to be unchanged by castration, thyroidectomy, adrenalectomy and LH-RH injection. The putative prolactin cells are characterized by large (400-600 nm), spherical or polmorphic, dense secretory granules stainable with acid fuchsin and aniline blue; prominent Golgi apparatus and well developed endoplasmic reticulum with densely packed, regularly parallel lamellae. They are found mainly in the cephalic lobe. The prolactin cells develop some vacuolization after adrenalectomy and undergo some degeneration after castration. The ACTH cells, which are restricted to the cephalic lobe, are identified by the dense, spherical granules (250-300 nm) that are stained with acid fuchsin. After adrenalectomy, they lose their secretory granules and are transformed into large, chromophobic adrenalectomy cells. TSH cells are so designated by their response to thyroidectomy including loss of their fine secretory granules and transformation to large, vacuolated thyroidectomy cells. We have found TSH cells and thyroidectomy cells only in the cephalic lobe. Basophilic cells, considered to be gonadotropes, occur in both the cephalic and caudal lobes. The gonadotropes of the cephalic lobe appear to have slightly larger (120-200 nm) granules than the caudal lobe (120-150 nm). However, after castration, the gonadotropes in both lobes become hypertrophied and vacuolated and are transformed into mutually indistinguishable castration cells. Twenty minutes after injection with LH-RH, the gonadotropes of both lobes increase in size and number, degranulate, develop vacuoles in the cytoplasm, and appear very similar to castration cells."} {"id": "PMID:167971", "title": "Cell types in the adenohypophysis of the Japanese quail and effects of injection of luteinizing hormone-releasing hormone.", "content": "The cells of the adenohypophysis of the Japanese quail were studied by both light and electron microscopy after exposure to long photoperiods or injection of lutenizing hormone-releasing hormone (LRH). Six cell types were identified in the adenohypophysis by examining alternate thick and thin sections by light and electron microscopy. In the cephalic lobe, there are four types of glandular cells. They are the prolactin cells, ACTH cells, TSH cells, and gonadotropic cells (FSH?). In the caudal lobe, there are two types of cells, STH cells and gonadotropic cells (LH?). After exposure to long daily photoperiods, gonadotropic cells in both lobes were strongly activated. They became larger and accumulated many granules. ACTH cells became vacuolated; granules were sparse. Synthetic LRH injection (10 mug/0.2 ml/day) for 10 days to the non-photostimulated quail stimulated certain numbers of the gonadotropic cells in the both lobes, although the response of the cells was less than that induced by photostimulation. No response was seen in the other cell types.", "contents": "Cell types in the adenohypophysis of the Japanese quail and effects of injection of luteinizing hormone-releasing hormone. The cells of the adenohypophysis of the Japanese quail were studied by both light and electron microscopy after exposure to long photoperiods or injection of lutenizing hormone-releasing hormone (LRH). Six cell types were identified in the adenohypophysis by examining alternate thick and thin sections by light and electron microscopy. In the cephalic lobe, there are four types of glandular cells. They are the prolactin cells, ACTH cells, TSH cells, and gonadotropic cells (FSH?). In the caudal lobe, there are two types of cells, STH cells and gonadotropic cells (LH?). After exposure to long daily photoperiods, gonadotropic cells in both lobes were strongly activated. They became larger and accumulated many granules. ACTH cells became vacuolated; granules were sparse. Synthetic LRH injection (10 mug/0.2 ml/day) for 10 days to the non-photostimulated quail stimulated certain numbers of the gonadotropic cells in the both lobes, although the response of the cells was less than that induced by photostimulation. No response was seen in the other cell types."} {"id": "PMID:167972", "title": "Vacuolated pinealocytes in the hedgehog (Erinaceus europaeus L.) and the mole (Talpa europaea L.).", "content": "Special cells in the hedgehog and mole pineal gland which are characterized by an enormous single vacuole were studied. The presence of secretory granules (in the hedgehog) and of paracrystalline structures (in the mole) in the cytoplasm of these cells indicates that they are pinealocytes.", "contents": "Vacuolated pinealocytes in the hedgehog (Erinaceus europaeus L.) and the mole (Talpa europaea L.). Special cells in the hedgehog and mole pineal gland which are characterized by an enormous single vacuole were studied. The presence of secretory granules (in the hedgehog) and of paracrystalline structures (in the mole) in the cytoplasm of these cells indicates that they are pinealocytes."} {"id": "PMID:167973", "title": "Ultrastructural study of the neural fat-body system in the cockroach Periplaneta americana.", "content": "The neural fat-body system of the ventral nerve cord in the cockroach Periplaneta americana was studied with the light and electron microscopes. This adipose tissue surrounds the connectives and extends over the ganglia. The adipose cells typically contain numerous extremely large lipid inclusions, pleomorphic lysosomes, and tightly packed glycogen granules. The neural lamella consists of a thick inner layer rich in collagen fibers and a thin outer layer of granular material. At points where the fat body is attenuated, this granular layer is split and the outer lamina is reflected superficially to ensheath and apparently to anchor the fat body.", "contents": "Ultrastructural study of the neural fat-body system in the cockroach Periplaneta americana. The neural fat-body system of the ventral nerve cord in the cockroach Periplaneta americana was studied with the light and electron microscopes. This adipose tissue surrounds the connectives and extends over the ganglia. The adipose cells typically contain numerous extremely large lipid inclusions, pleomorphic lysosomes, and tightly packed glycogen granules. The neural lamella consists of a thick inner layer rich in collagen fibers and a thin outer layer of granular material. At points where the fat body is attenuated, this granular layer is split and the outer lamina is reflected superficially to ensheath and apparently to anchor the fat body."} {"id": "PMID:167974", "title": "The ultrastructure of topical cutaneous calcinosis.", "content": "Mineralized plaques, which develop at the site of repeated subcutaneous injections of 100 mug KMnO4/0.2 H2O in rats, were investigated by electron microscopy. The newly formed, delineated, white plaque tissue at the injection site consisted of numerous, mostly unaltered fibroblasts and collagen fibers, without participation of inflammatory cells. Some signs of cell injury were found in the center of the lesions. Numerous, irregularly distributed, small, mineralized foci were seen near the fibroblasts. These were formed by aggregation of small needle-like units (50 A in diameter and 0.05-2.0 mum long). These needle-shaped units were found either in vesicular, cell derived structures, considered to be shed cell fragments, or on collagen fibers. Intramitochondrial deposits of such needle like units were seen frequently. Fusion of smaller mineralized foci to larger plaques occured and then needle-shaped units were seen at the periphery of the electron-dense lesions. Hypotheses concerning the mechanism of experimental cutaneous calcinosis (soft tissue mineralization) are discussed and related to the findings of this study. Probable intracellular crystal deposition and mineralization in cell-derived structures were shown for the first time in topical cutaneous calcinosis.", "contents": "The ultrastructure of topical cutaneous calcinosis. Mineralized plaques, which develop at the site of repeated subcutaneous injections of 100 mug KMnO4/0.2 H2O in rats, were investigated by electron microscopy. The newly formed, delineated, white plaque tissue at the injection site consisted of numerous, mostly unaltered fibroblasts and collagen fibers, without participation of inflammatory cells. Some signs of cell injury were found in the center of the lesions. Numerous, irregularly distributed, small, mineralized foci were seen near the fibroblasts. These were formed by aggregation of small needle-like units (50 A in diameter and 0.05-2.0 mum long). These needle-shaped units were found either in vesicular, cell derived structures, considered to be shed cell fragments, or on collagen fibers. Intramitochondrial deposits of such needle like units were seen frequently. Fusion of smaller mineralized foci to larger plaques occured and then needle-shaped units were seen at the periphery of the electron-dense lesions. Hypotheses concerning the mechanism of experimental cutaneous calcinosis (soft tissue mineralization) are discussed and related to the findings of this study. Probable intracellular crystal deposition and mineralization in cell-derived structures were shown for the first time in topical cutaneous calcinosis."} {"id": "PMID:167975", "title": "Histochemical, ultrastructural and hormonal studies on the pars distalis of the echidna (Tachyglossus aculeatus).", "content": "There were no consistent significant differences between the concentrations of luteinizing hormone (LH) and adrenocorticotrophin (ACTH) in the rostral compared with the caudal zone of the echidna pars distalis. This suggests that LH is secreted by cells containing S-type granules (probably corresponding to secretory vesicles 200-300 nm diameter) which are distributed throughout the gland. Some of the cells containing vesicles 100-200 nm diameter, seen in small numbers in both zones of the gland, may be responsible for the secretion of ACTH. The concentration of pituitary LH is in the range of that found in eutherian mammals, but the concentration of ACTH is lower than that reported for other vertebrates, and this may be linked causally with the remarkably low rate of corticosteroid secretion in the echidna. The absence of significantly increased levels of pituitary LH and ACTH in a chronically orchidectomized and adrenalectomized animal adds to other evidence which suggests that mechanisms involving a negative feedback of steroid hormones on the hypothalamo-hypophysial axis may not be fully developed in the echidna.", "contents": "Histochemical, ultrastructural and hormonal studies on the pars distalis of the echidna (Tachyglossus aculeatus). There were no consistent significant differences between the concentrations of luteinizing hormone (LH) and adrenocorticotrophin (ACTH) in the rostral compared with the caudal zone of the echidna pars distalis. This suggests that LH is secreted by cells containing S-type granules (probably corresponding to secretory vesicles 200-300 nm diameter) which are distributed throughout the gland. Some of the cells containing vesicles 100-200 nm diameter, seen in small numbers in both zones of the gland, may be responsible for the secretion of ACTH. The concentration of pituitary LH is in the range of that found in eutherian mammals, but the concentration of ACTH is lower than that reported for other vertebrates, and this may be linked causally with the remarkably low rate of corticosteroid secretion in the echidna. The absence of significantly increased levels of pituitary LH and ACTH in a chronically orchidectomized and adrenalectomized animal adds to other evidence which suggests that mechanisms involving a negative feedback of steroid hormones on the hypothalamo-hypophysial axis may not be fully developed in the echidna."} {"id": "PMID:167976", "title": "Ultrastructure of the budgerigar testis during a photoperiodically induced cycle.", "content": "Spermatogenesis in the Budgerigar can be arrested by reducing the birds' photoperiod to 8 hours of daylight or less. When this occurs, Sertoli cell cytoplasm shows a great increase in the size and number of residual bodies, while the smooth endoplasmic reticulum is reduced. If the bird is kept at 8 hours of daylight for some weeks large lipid droplets are seen in Sertoli cytoplasm, and degenerated spermatids are apparently phagocytosed. The interstitium shows fewer active Leydig cells, a paucity of lipids and occasional ovoid mitochondria. The basal lamellae of the tubule which are thick and convoluted before and during spermatogenesis become thinner and straighter. It is thought that these morphological changes reflect changes in metabolic activity.", "contents": "Ultrastructure of the budgerigar testis during a photoperiodically induced cycle. Spermatogenesis in the Budgerigar can be arrested by reducing the birds' photoperiod to 8 hours of daylight or less. When this occurs, Sertoli cell cytoplasm shows a great increase in the size and number of residual bodies, while the smooth endoplasmic reticulum is reduced. If the bird is kept at 8 hours of daylight for some weeks large lipid droplets are seen in Sertoli cytoplasm, and degenerated spermatids are apparently phagocytosed. The interstitium shows fewer active Leydig cells, a paucity of lipids and occasional ovoid mitochondria. The basal lamellae of the tubule which are thick and convoluted before and during spermatogenesis become thinner and straighter. It is thought that these morphological changes reflect changes in metabolic activity."} {"id": "PMID:167977", "title": "On degeneration of peptidergic neurosecretory fibres in the albino rat.", "content": "Three types of degenerating peptidergic neurosecretory fibres have been found in the posterior pituitary of chronically dehydrated albino rats. \"Dark\" neurosecretory fibres and their swellings contain neurosecretory granules, neurotubules, shrunken mitochondria and diffusely distributed fine dense material. Some swellings are filled with synaptic vesicles and/or conglomerations of dense membranes. The transitional forms exist between these fibres and extracellular accumulations of electron dense material. Synaptic vesicles, single neurosecretory granules, lipid-like droplets and lamellar bodies occur in the latter. Some neurosecretory fibres and swellings have numerous polymorphous inclusions arising due to degradation of secretory inclusions and organelles, mitochondria and neurotubules in particular. \"Dark\" neurosecretory elements and those with numerous polymorphous inclusions are enveloped by pituicyte cytoplasm. Sometimes the plasma membranes both of the pituicytes and neurosecretory fibres are destroyed or transformed into a multi-membrane complex. It is assumed that pituicytes may phagocytize degenerating neurosecretory elements. N urosecretory fibres with a locally dissolved neuroplasm and/or large lucent vacuoles seem to be due to axonal degeneration by the \"light\" type. These neurosecretory elements, the largest of them in particular, may transform into large cavities bordered by a membrane and containing flake-like material and single-membrane vacuoles. Degeneration of neurosecretory elements seems to occur mainly due to hyperfunction of the hypothalamo-hypophysial neurosecretory system.", "contents": "On degeneration of peptidergic neurosecretory fibres in the albino rat. Three types of degenerating peptidergic neurosecretory fibres have been found in the posterior pituitary of chronically dehydrated albino rats. \"Dark\" neurosecretory fibres and their swellings contain neurosecretory granules, neurotubules, shrunken mitochondria and diffusely distributed fine dense material. Some swellings are filled with synaptic vesicles and/or conglomerations of dense membranes. The transitional forms exist between these fibres and extracellular accumulations of electron dense material. Synaptic vesicles, single neurosecretory granules, lipid-like droplets and lamellar bodies occur in the latter. Some neurosecretory fibres and swellings have numerous polymorphous inclusions arising due to degradation of secretory inclusions and organelles, mitochondria and neurotubules in particular. \"Dark\" neurosecretory elements and those with numerous polymorphous inclusions are enveloped by pituicyte cytoplasm. Sometimes the plasma membranes both of the pituicytes and neurosecretory fibres are destroyed or transformed into a multi-membrane complex. It is assumed that pituicytes may phagocytize degenerating neurosecretory elements. N urosecretory fibres with a locally dissolved neuroplasm and/or large lucent vacuoles seem to be due to axonal degeneration by the \"light\" type. These neurosecretory elements, the largest of them in particular, may transform into large cavities bordered by a membrane and containing flake-like material and single-membrane vacuoles. Degeneration of neurosecretory elements seems to occur mainly due to hyperfunction of the hypothalamo-hypophysial neurosecretory system."} {"id": "PMID:167978", "title": "Adrenocortical response in the duck exposed to corticosteroid administration and salt loading.", "content": "The functional zonation in the adrenocortical tissue of the duck was experimentally investigated after chronic administration of corticosteroids of different types (corticosterone, desoxycorticosterone, dexamethasone) and salt loading (chlorides of sodium and potassium). The cytomorphology of the interrenal cells belonging to subcapsular and central zones was explored by light- and electron microscopy and by biochemical analysis of plasma corticosterone. Corticoid-induced involution of the interrenal tissue, or hyperactivity elicited by salt loading were evident in both subcapsular and central regions of the gland. In the duck the adrenocortical tissue appears to be devoid of steroidogenic functional differentiation. The modifications of different cellular organelles and inclusions can be explained in the light of known concepts about corticosteroid metabolism. The depression of plasma corticosterone titre in corticosteroid-treated animals agrees with the image of cytological inhibition. The lowered corticosterone value in KCl-loaded ducks signifies increased peripheral metabolism of this hormone. The hypercorticosteronemia in NaCl-loaded ducks is probably related to activation of the nasal gland under osmotic stress.", "contents": "Adrenocortical response in the duck exposed to corticosteroid administration and salt loading. The functional zonation in the adrenocortical tissue of the duck was experimentally investigated after chronic administration of corticosteroids of different types (corticosterone, desoxycorticosterone, dexamethasone) and salt loading (chlorides of sodium and potassium). The cytomorphology of the interrenal cells belonging to subcapsular and central zones was explored by light- and electron microscopy and by biochemical analysis of plasma corticosterone. Corticoid-induced involution of the interrenal tissue, or hyperactivity elicited by salt loading were evident in both subcapsular and central regions of the gland. In the duck the adrenocortical tissue appears to be devoid of steroidogenic functional differentiation. The modifications of different cellular organelles and inclusions can be explained in the light of known concepts about corticosteroid metabolism. The depression of plasma corticosterone titre in corticosteroid-treated animals agrees with the image of cytological inhibition. The lowered corticosterone value in KCl-loaded ducks signifies increased peripheral metabolism of this hormone. The hypercorticosteronemia in NaCl-loaded ducks is probably related to activation of the nasal gland under osmotic stress."} {"id": "PMID:167979", "title": "Ultrastructural studies on the intranuclear inclusions of the rabbit adenohypophysis in vivo and in vitro.", "content": "Intranuclear inclusions of three basic types are described in various parts of the rabbit adenohypophysis in vivo and in organ and cell cultures. These inclusions are mostly found in the postnatal tissue but occur in both glandular and non-glandular cells. A comparison is made with similar structures encountered elsewhere. Their significance is not known.", "contents": "Ultrastructural studies on the intranuclear inclusions of the rabbit adenohypophysis in vivo and in vitro. Intranuclear inclusions of three basic types are described in various parts of the rabbit adenohypophysis in vivo and in organ and cell cultures. These inclusions are mostly found in the postnatal tissue but occur in both glandular and non-glandular cells. A comparison is made with similar structures encountered elsewhere. Their significance is not known."} {"id": "PMID:167980", "title": "Different secretory responses of periinsular and other acini in the rat pancreas after pilocarpine injection.", "content": "Histological, histochemical, and electron microscopical investigations of the rat pancreas, one to five hours after pilocarpine injection (4 mg in 1 ml normal saline solution), showed different secretory responses in periinsular and apoinsular acinar cells. The responsiveness to parasympathetic stimulation is markedly retarded and weakened in the periinsular area. It is supposed that the halo phenomenon is related not only to an inhibition of the secretion, but also to a longer lasting synthesis of zymogen granules. The insular hormones, glucagon and insulin, which are possibly locally enriched by insulo-acinar capillary anastomoses or by diffusion, may be involved in the regulation of activity in the periinsular cells.", "contents": "Different secretory responses of periinsular and other acini in the rat pancreas after pilocarpine injection. Histological, histochemical, and electron microscopical investigations of the rat pancreas, one to five hours after pilocarpine injection (4 mg in 1 ml normal saline solution), showed different secretory responses in periinsular and apoinsular acinar cells. The responsiveness to parasympathetic stimulation is markedly retarded and weakened in the periinsular area. It is supposed that the halo phenomenon is related not only to an inhibition of the secretion, but also to a longer lasting synthesis of zymogen granules. The insular hormones, glucagon and insulin, which are possibly locally enriched by insulo-acinar capillary anastomoses or by diffusion, may be involved in the regulation of activity in the periinsular cells."} {"id": "PMID:167981", "title": "Inhibition of protease activity in cultures of rous sarcoma virus-transformed cells: effect on the transformed phenotype.", "content": "We have examined the role of proteolytic activity in the genesis and maintenance of the transformed phenotype by growing cultures of chick embryo fibroblasts transfromed by Rous sarcoma virus either in medium containing plasminogen-free serum or in medium to which protease inhibitors were added. Alterations in morphology, adhesiveness, and hexose transport were used as markers for the transformed state. Addition of the trypsin inhibitors NPGB or Soy Bean Trypsin Inhibitor at concentrations which inhibited transformation-associated fibrinolysis restored adhesiveness and morphology to near normal, but did not affect the rate of hexose transport. Growth of Rous-infected cells in plasminogen-free medium blocked the appearance of morphological and adhesive alterations, but allowed the rate of hexose transport to increase to the transformed level. Thus we were able to separate the appearance of transformation-specific changes in morphology and adhesiveness (which apparently require fibrinolytic activity) from the increased rate of hexose transport (which is independent of fibrinolytic activity). Another trypsin inhibitor, TLCK, although it did not inhibit fibrinolysis, was very effective at restoring adhesiveness and morphology as well as hexose transport to normal. This raises the possibility that there is another, perhaps earlier, protease involved in the genesis of the transformed phenotype.", "contents": "Inhibition of protease activity in cultures of rous sarcoma virus-transformed cells: effect on the transformed phenotype. We have examined the role of proteolytic activity in the genesis and maintenance of the transformed phenotype by growing cultures of chick embryo fibroblasts transfromed by Rous sarcoma virus either in medium containing plasminogen-free serum or in medium to which protease inhibitors were added. Alterations in morphology, adhesiveness, and hexose transport were used as markers for the transformed state. Addition of the trypsin inhibitors NPGB or Soy Bean Trypsin Inhibitor at concentrations which inhibited transformation-associated fibrinolysis restored adhesiveness and morphology to near normal, but did not affect the rate of hexose transport. Growth of Rous-infected cells in plasminogen-free medium blocked the appearance of morphological and adhesive alterations, but allowed the rate of hexose transport to increase to the transformed level. Thus we were able to separate the appearance of transformation-specific changes in morphology and adhesiveness (which apparently require fibrinolytic activity) from the increased rate of hexose transport (which is independent of fibrinolytic activity). Another trypsin inhibitor, TLCK, although it did not inhibit fibrinolysis, was very effective at restoring adhesiveness and morphology as well as hexose transport to normal. This raises the possibility that there is another, perhaps earlier, protease involved in the genesis of the transformed phenotype."} {"id": "PMID:167982", "title": "Nucleic acid hybridization using DNA covalently coupled to cellulose.", "content": "We describe a method for linking RNA and DNA covalently to finely divided cellulose through a diazotized aryl amine, which reacts primarily with guanine and uracil (thymine) residues of single strands. The high efficiency of coupling and high capacity of the cellulose for nucleic acid make possible a product with as much as 67 mug of nucleic acid per mg of cellulose. The product is especially suitable for hybridization experiments where very low backgrounds are important, and it is stable in 99% formamide at 80 degrees C so that hybridized nucleic acid can be recovered easily. Full length linear Simian Virus 40 (SV40) DNA, produced by cleavage of SV40(I) DNA with S1 nuclease, can be coupled to diazo cellulose with an efficiency of 80-90%, and is effective in hybridization experiments with SV40 DNA, complementary RNA synthesized in vitro from SV40(I) DNA with E. coli RNA polymerase, and the SV40-specific fraction of total RNA from SV40-infected and transformed cells. In these experiments an excess of cellulose-bound DNA was used, and the efficiency of hybridization was about 90% when ribonuclease treatment of the hybrids was omitted.", "contents": "Nucleic acid hybridization using DNA covalently coupled to cellulose. We describe a method for linking RNA and DNA covalently to finely divided cellulose through a diazotized aryl amine, which reacts primarily with guanine and uracil (thymine) residues of single strands. The high efficiency of coupling and high capacity of the cellulose for nucleic acid make possible a product with as much as 67 mug of nucleic acid per mg of cellulose. The product is especially suitable for hybridization experiments where very low backgrounds are important, and it is stable in 99% formamide at 80 degrees C so that hybridized nucleic acid can be recovered easily. Full length linear Simian Virus 40 (SV40) DNA, produced by cleavage of SV40(I) DNA with S1 nuclease, can be coupled to diazo cellulose with an efficiency of 80-90%, and is effective in hybridization experiments with SV40 DNA, complementary RNA synthesized in vitro from SV40(I) DNA with E. coli RNA polymerase, and the SV40-specific fraction of total RNA from SV40-infected and transformed cells. In these experiments an excess of cellulose-bound DNA was used, and the efficiency of hybridization was about 90% when ribonuclease treatment of the hybrids was omitted."} {"id": "PMID:167983", "title": "Effects of cycloheximide on virus RNA replication in an inducible line of polyoma-transformed rat cells.", "content": "In this article, we describe two distinct effects of cycloheximide (CH), a potent inhibitior of protein synthesis, on the replication of polyoma virus (PV) DNA in an inducible line of PV-transformed rat cells (LPT cells). Exposure of LPT cells to CH causes up to an 8 fold increase in the cellular concentration of PV DNA determined by molecular hybridization. The same treatment inhibits cell division and chromosomal DNA replication. However, the amount of chromosomal DNA per cell is not affected by the drug. In LPT cells treated with mitomycin C (MMC), PV DNA replication is enhanced after 7 hr. During the period extending from 7 hr to 24 hr, the concentration of virus DNA increases at least 100 fold. CH added to the cells 0-7 hr after treatment with MMC inhibits the replication of PV DNA by 90-100%. The inhibition is less effective in cells exposed to CH from 7 hr and on. The inhibitory effect is reversible: virus DNA synthesis is resumed after removal of CH from the growth medium. Thus CH acts as an inducer of virus DNA synthesis in cells whose resident viral genome is repressed, but inhibits the autonomous replication of the activated genome following induction with MMC.", "contents": "Effects of cycloheximide on virus RNA replication in an inducible line of polyoma-transformed rat cells. In this article, we describe two distinct effects of cycloheximide (CH), a potent inhibitior of protein synthesis, on the replication of polyoma virus (PV) DNA in an inducible line of PV-transformed rat cells (LPT cells). Exposure of LPT cells to CH causes up to an 8 fold increase in the cellular concentration of PV DNA determined by molecular hybridization. The same treatment inhibits cell division and chromosomal DNA replication. However, the amount of chromosomal DNA per cell is not affected by the drug. In LPT cells treated with mitomycin C (MMC), PV DNA replication is enhanced after 7 hr. During the period extending from 7 hr to 24 hr, the concentration of virus DNA increases at least 100 fold. CH added to the cells 0-7 hr after treatment with MMC inhibits the replication of PV DNA by 90-100%. The inhibition is less effective in cells exposed to CH from 7 hr and on. The inhibitory effect is reversible: virus DNA synthesis is resumed after removal of CH from the growth medium. Thus CH acts as an inducer of virus DNA synthesis in cells whose resident viral genome is repressed, but inhibits the autonomous replication of the activated genome following induction with MMC."} {"id": "PMID:167984", "title": "Fibrin overlay methods for the detection of single transformed cells and colonies of transformed cells.", "content": "Fibrin overlay methods are described which can detect the plasminogen activator produced by single transformed cells or small colonies of transformed cells. These methods were applied to malignant cells derived from humans, mice, hamsters, rats, and chicks. The lysis observed was plasminogen dependent. Transformation of chicken cells by Rous sarcoma virus was detected 4 days after infection. The number of lysis zones produced was proportional to the virus inoculum and was identical to the number of morphologically determined foci. These methods may also have application in model systems for scoring transformation by chemicals. Transformed mouse and chicken cells were detected at the single cell level and the number of lysis zones produced was dependent on the number of cells present, the time of incubation, and the concentration of plasminogen.", "contents": "Fibrin overlay methods for the detection of single transformed cells and colonies of transformed cells. Fibrin overlay methods are described which can detect the plasminogen activator produced by single transformed cells or small colonies of transformed cells. These methods were applied to malignant cells derived from humans, mice, hamsters, rats, and chicks. The lysis observed was plasminogen dependent. Transformation of chicken cells by Rous sarcoma virus was detected 4 days after infection. The number of lysis zones produced was proportional to the virus inoculum and was identical to the number of morphologically determined foci. These methods may also have application in model systems for scoring transformation by chemicals. Transformed mouse and chicken cells were detected at the single cell level and the number of lysis zones produced was dependent on the number of cells present, the time of incubation, and the concentration of plasminogen."} {"id": "PMID:167985", "title": "Determination of limb bud chondrocytes during a transient block of the cell cycle.", "content": "The process of determination is studied by using a cell culture system derived from dissociated chick embryo limb buds. When limb bud cells obtained from embryos younger than stage 25 (undertermined) are temporarily prevented from passing through the cell cycle (either by maintaining the cells on a petri dish or in the presence of high concentrations of cyclic AMP, both of which depress thymidine-H(3) incorporation), some cells subsequently form cartilage colonies. These results support the hypothesis that a temporary block at some stage in the cell cycle causes mesoblasts to acquire the capacity to differentiate into cartilage cells.", "contents": "Determination of limb bud chondrocytes during a transient block of the cell cycle. The process of determination is studied by using a cell culture system derived from dissociated chick embryo limb buds. When limb bud cells obtained from embryos younger than stage 25 (undertermined) are temporarily prevented from passing through the cell cycle (either by maintaining the cells on a petri dish or in the presence of high concentrations of cyclic AMP, both of which depress thymidine-H(3) incorporation), some cells subsequently form cartilage colonies. These results support the hypothesis that a temporary block at some stage in the cell cycle causes mesoblasts to acquire the capacity to differentiate into cartilage cells."} {"id": "PMID:167986", "title": "Adaptation of the mitochondrial systems of Rhodotorula gracilis to low oxygen pressure.", "content": "The obligate aerobic yeast, Rhodotorula gracilis, was grown in a liquid minimal medium at 1 mm Hg partial pressure of oxygen, conditions under which growth (measured as the increase in total protein) is reduced to 30% of the maximum rate. A significant increase in the ratio between mitochondrial oxidative enzymes and total protein occurs rapidly under these conditions. A concurrent increase in the ratio area of mitochondria/area of cytoplasm was also observed. The relative increase in mitochondrial enzymes, oxidase activities and mitochondrial membranes is due to the inhibition affecting the increase in cytoplasmic structures more significantly than the increase in mitochondrial structures at low pO2. The difference between mitochondrial and cytoplasmic syntheses cannot be ascribed to changes in the availability of ATP but it might rest with some other oxygen-utilising process (pyrimidine redox coenzymes, synthesis of sterols). The experimental conditions studied appear to offer a valuable tool for the investigation of the relationships between mitochondrial and cytoplasmic structures.", "contents": "Adaptation of the mitochondrial systems of Rhodotorula gracilis to low oxygen pressure. The obligate aerobic yeast, Rhodotorula gracilis, was grown in a liquid minimal medium at 1 mm Hg partial pressure of oxygen, conditions under which growth (measured as the increase in total protein) is reduced to 30% of the maximum rate. A significant increase in the ratio between mitochondrial oxidative enzymes and total protein occurs rapidly under these conditions. A concurrent increase in the ratio area of mitochondria/area of cytoplasm was also observed. The relative increase in mitochondrial enzymes, oxidase activities and mitochondrial membranes is due to the inhibition affecting the increase in cytoplasmic structures more significantly than the increase in mitochondrial structures at low pO2. The difference between mitochondrial and cytoplasmic syntheses cannot be ascribed to changes in the availability of ATP but it might rest with some other oxygen-utilising process (pyrimidine redox coenzymes, synthesis of sterols). The experimental conditions studied appear to offer a valuable tool for the investigation of the relationships between mitochondrial and cytoplasmic structures."} {"id": "PMID:167987", "title": "The inhibitory effect of glucose on the differentiation of trophic Hartmannella culbertsoni into viable cysts.", "content": "During encystation of Hartmannella culbertsoni induced by taurine or epinephrine, 60-70% of the reserve glycogen is degraded. Glycogen phosphorylase is activated and glycogen synthetase is inhibited after 6-8 hr of exposure to the encystation medium. The carbon skeleton of glycogen but not that of protein is utilised in the synthesis of cyst wall cellulose. Exogenously added glucose (225 and 550 mM) blocks encystation, degradation of glycogen and synthesis of cellulose. Cyclic AMP synthesis is also very much reduced in cells exposed to glucose.", "contents": "The inhibitory effect of glucose on the differentiation of trophic Hartmannella culbertsoni into viable cysts. During encystation of Hartmannella culbertsoni induced by taurine or epinephrine, 60-70% of the reserve glycogen is degraded. Glycogen phosphorylase is activated and glycogen synthetase is inhibited after 6-8 hr of exposure to the encystation medium. The carbon skeleton of glycogen but not that of protein is utilised in the synthesis of cyst wall cellulose. Exogenously added glucose (225 and 550 mM) blocks encystation, degradation of glycogen and synthesis of cellulose. Cyclic AMP synthesis is also very much reduced in cells exposed to glucose."} {"id": "PMID:167988", "title": "[Small-cell carcinoma of the larynx].", "content": "In a 69-year-old man by biopsy and for the first time on necropsy a primary small-cell carcinoma of the laryngeal ventricle with metastases into the liver was detected and confirmed. Under the electron microscope in the cells endocrine granules were found which were not argyrophil.", "contents": "[Small-cell carcinoma of the larynx]. In a 69-year-old man by biopsy and for the first time on necropsy a primary small-cell carcinoma of the laryngeal ventricle with metastases into the liver was detected and confirmed. Under the electron microscope in the cells endocrine granules were found which were not argyrophil."} {"id": "PMID:167989", "title": "Reversibility of lysosomal and glucose 6-phosphatase changes produced in the rat liver by dimethylnitrosamine.", "content": "The present investigation was undertaken to discover whether repeated doses of dimethylnitrosamine (DMNA) could produce a cumulative toxic effect on the rat liver. For this purpose doses were selected at a level just too low to produce cytopathological changes, as indicated by depression of glucose-6-phosphatase and induction of autophagic vacuoles (AV) in hepatocytes, when given once only. Single subcutaneous injections of 10 or 3 mg/kg induced these cytopathological changes in the centrilobular (CLB) hepatic cells but when the dose was reduced to 1 mg/kg no such changes were seen. After daily administration of 1 mg/kg for 4 or 8 weeks we observed both glucose-6-phosphatase depression and autophagy, and in addition there was marked hypertrophy of the rough endoplasmic reticulum, nucleolar microsegregation and the appearance of distorted, often ring-shaped mitochondria with shortened cristae. Kupffer cells exhibited a marked increase in lysosomal activity. With the exception of mitochondrial changes and Kupffer cell activity this same picture was observed, although in milder form, when the dose administered was 0.3 or 0.1 mg/kg daily for the same period. When treatment was continued for 12 weeks, however, the only differences from control rats were the presence of hypertrophied rough endoplasmic reticulum (RER) at all three dose levels, nucleolar microsegregation at the upper two dose levels, and pronounced Kupffer cell activity at the top dose. These findings indicate that cumulative cytopathologic effects occur only up to 8 weeks at the dose levels studied but hypertrophy of RER and increased Kupffer cell activity persist up to 12 weeks.", "contents": "Reversibility of lysosomal and glucose 6-phosphatase changes produced in the rat liver by dimethylnitrosamine. The present investigation was undertaken to discover whether repeated doses of dimethylnitrosamine (DMNA) could produce a cumulative toxic effect on the rat liver. For this purpose doses were selected at a level just too low to produce cytopathological changes, as indicated by depression of glucose-6-phosphatase and induction of autophagic vacuoles (AV) in hepatocytes, when given once only. Single subcutaneous injections of 10 or 3 mg/kg induced these cytopathological changes in the centrilobular (CLB) hepatic cells but when the dose was reduced to 1 mg/kg no such changes were seen. After daily administration of 1 mg/kg for 4 or 8 weeks we observed both glucose-6-phosphatase depression and autophagy, and in addition there was marked hypertrophy of the rough endoplasmic reticulum, nucleolar microsegregation and the appearance of distorted, often ring-shaped mitochondria with shortened cristae. Kupffer cells exhibited a marked increase in lysosomal activity. With the exception of mitochondrial changes and Kupffer cell activity this same picture was observed, although in milder form, when the dose administered was 0.3 or 0.1 mg/kg daily for the same period. When treatment was continued for 12 weeks, however, the only differences from control rats were the presence of hypertrophied rough endoplasmic reticulum (RER) at all three dose levels, nucleolar microsegregation at the upper two dose levels, and pronounced Kupffer cell activity at the top dose. These findings indicate that cumulative cytopathologic effects occur only up to 8 weeks at the dose levels studied but hypertrophy of RER and increased Kupffer cell activity persist up to 12 weeks."} {"id": "PMID:167992", "title": "[Enzymatic characteristics of the catalytic subunit of the protein kinase complex of human lymphocytes].", "content": "In earlier reports we have shown the existence in human lymphocytes homogenate, of a cyclic-AMP dependent protein-kinase activity. We demonstrate by affinity chromatography that two subunits display respectively cyclic-AMP binding and phosphorylating properties. Divalent cations such as Ca++, Mg++ or Mn++ are required for enzymatic activity. ATP which is an obligatory cosubstrate acts as an inhibitor when its concentration is higher than 10(-6)M.", "contents": "[Enzymatic characteristics of the catalytic subunit of the protein kinase complex of human lymphocytes]. In earlier reports we have shown the existence in human lymphocytes homogenate, of a cyclic-AMP dependent protein-kinase activity. We demonstrate by affinity chromatography that two subunits display respectively cyclic-AMP binding and phosphorylating properties. Divalent cations such as Ca++, Mg++ or Mn++ are required for enzymatic activity. ATP which is an obligatory cosubstrate acts as an inhibitor when its concentration is higher than 10(-6)M."} {"id": "PMID:167993", "title": "[The binding of tritiated dexamethasone to lymphocytes of normal and leukemic subjects].", "content": "Specific binding sites for 3H-dexamethasone, possessing the characteristics of glucocorticoid receptors, were demonstrated in normal human circulating lymphocytes. The number of glucocorticoid receptors was found different from normal in half of the acute or chronic lymphoid leukaemias studied. A correlation between the number of glucocorticoid receptors and the therapeutical benefit of the glucocorticoid administration will be performed, including these preliminary observations.", "contents": "[The binding of tritiated dexamethasone to lymphocytes of normal and leukemic subjects]. Specific binding sites for 3H-dexamethasone, possessing the characteristics of glucocorticoid receptors, were demonstrated in normal human circulating lymphocytes. The number of glucocorticoid receptors was found different from normal in half of the acute or chronic lymphoid leukaemias studied. A correlation between the number of glucocorticoid receptors and the therapeutical benefit of the glucocorticoid administration will be performed, including these preliminary observations."} {"id": "PMID:167994", "title": "[Standardization of \"exchange\" techniques to measure estradiol receptors in extracts exposed to biospecific adsorbants].", "content": "The measurement of the binding of steroid hormone receptors to biospecific adsorbants requires the development of \"exchange\" techniques. Two types of techniques based on the principle of differential dissociation were standardized: solid phase exchange with hydroxylapatite and liquid phase exchange with adsorption of the ligand to charcoal dextran. In both cases, binding of oestradiol to its receptor was measured in calf uterine cytosol extracts. Results obtained by both techniques were comparable. The half-times of the oestradiol-receptor complex dissociation determined from exchange kinetics are on the same order as those obtained by direct methods used in previous studies.", "contents": "[Standardization of \"exchange\" techniques to measure estradiol receptors in extracts exposed to biospecific adsorbants]. The measurement of the binding of steroid hormone receptors to biospecific adsorbants requires the development of \"exchange\" techniques. Two types of techniques based on the principle of differential dissociation were standardized: solid phase exchange with hydroxylapatite and liquid phase exchange with adsorption of the ligand to charcoal dextran. In both cases, binding of oestradiol to its receptor was measured in calf uterine cytosol extracts. Results obtained by both techniques were comparable. The half-times of the oestradiol-receptor complex dissociation determined from exchange kinetics are on the same order as those obtained by direct methods used in previous studies."} {"id": "PMID:167995", "title": "[Radioimmunologic assay of plasma corticotropin in the green frog, Rana esculenta L].", "content": "In the green Frog (Rana esculenta) the plasma contains a polypeptide immunologically related to human and porcine corticotropins. A radiommunoassay capable of detecting 4.10-12 g hog ACTH has been used for a direct plasma ACTH assay in the Frog. Using this method, the ACTH rate was determined both in untreated frogs and in animals under various experimental conditions.", "contents": "[Radioimmunologic assay of plasma corticotropin in the green frog, Rana esculenta L]. In the green Frog (Rana esculenta) the plasma contains a polypeptide immunologically related to human and porcine corticotropins. A radiommunoassay capable of detecting 4.10-12 g hog ACTH has been used for a direct plasma ACTH assay in the Frog. Using this method, the ACTH rate was determined both in untreated frogs and in animals under various experimental conditions."} {"id": "PMID:167996", "title": "[The effect of gonadotropic hormones and the fetal hypophysis on testosterone production by the testis of 18 day mouse fetuses in organ culture].", "content": "The production of testosterone (measured by radioimmuno-assay) by the 18-day-old mouse fetal testis may be stimulated specifically by ovine LH (1 ng, p less than 0.005) and HCG in organ culture. A stimulation by FSH is observed only with high doses (10 mug, p less than 0.0005). Prolactin and ACTH have no effect. Age-matched fetal pituitaries increase significantly the testosterone production in the culture medium (p less than 0.0005).", "contents": "[The effect of gonadotropic hormones and the fetal hypophysis on testosterone production by the testis of 18 day mouse fetuses in organ culture]. The production of testosterone (measured by radioimmuno-assay) by the 18-day-old mouse fetal testis may be stimulated specifically by ovine LH (1 ng, p less than 0.005) and HCG in organ culture. A stimulation by FSH is observed only with high doses (10 mug, p less than 0.0005). Prolactin and ACTH have no effect. Age-matched fetal pituitaries increase significantly the testosterone production in the culture medium (p less than 0.0005)."} {"id": "PMID:167997", "title": "[Plasmids controlling the resistance to several antibiotics in C. perfringens type A, strain 659].", "content": "A strain of C. perfringens type A, isolated from a patient, was found to be resistant to four antibiotics: tetracycline (Tet), chloramph\u00e9nicol (Chl), erythromycin (Ero) and clindamycin (Cli). Clones resistant to only two drugs (Tet-Chl or Ero-Cli), or sensitive to all drugs were found in cultures of the wild-type strain treated by acridine dyes or ethidium bromide. DNA analysis by equilibrium centrifugation confirmed that the original strain contains two resistance plasmids, one called Rip 401 (Tet-Chl) and the other Rip 402 (Ero-Cli), which represent respectively 1.8 +/- 0.2% and 2.3 +/- 0.2% of the total amount of DNA in this strain of Cl. perfrigens.", "contents": "[Plasmids controlling the resistance to several antibiotics in C. perfringens type A, strain 659]. A strain of C. perfringens type A, isolated from a patient, was found to be resistant to four antibiotics: tetracycline (Tet), chloramph\u00e9nicol (Chl), erythromycin (Ero) and clindamycin (Cli). Clones resistant to only two drugs (Tet-Chl or Ero-Cli), or sensitive to all drugs were found in cultures of the wild-type strain treated by acridine dyes or ethidium bromide. DNA analysis by equilibrium centrifugation confirmed that the original strain contains two resistance plasmids, one called Rip 401 (Tet-Chl) and the other Rip 402 (Ero-Cli), which represent respectively 1.8 +/- 0.2% and 2.3 +/- 0.2% of the total amount of DNA in this strain of Cl. perfrigens."} {"id": "PMID:167998", "title": "[The effect of alloxan on the multiplication of different types of normal or cancerous cells, and on the transformation of chick embryo fibroblasts by Rous virus in vitro].", "content": "The action of alloxan was studied in vitro, on different categories of normal or cancerous cells. At concentrations of 250 and 350 gamma/ml, alloxan does not significantly inhibit the growth of normal cells, whereas it does inhibit the growth of cancerous cells. Furthermore, alloxan inhibits infection and transformation of chicken-embryo fibroblasts infected by the Rous virus.", "contents": "[The effect of alloxan on the multiplication of different types of normal or cancerous cells, and on the transformation of chick embryo fibroblasts by Rous virus in vitro]. The action of alloxan was studied in vitro, on different categories of normal or cancerous cells. At concentrations of 250 and 350 gamma/ml, alloxan does not significantly inhibit the growth of normal cells, whereas it does inhibit the growth of cancerous cells. Furthermore, alloxan inhibits infection and transformation of chicken-embryo fibroblasts infected by the Rous virus."} {"id": "PMID:167999", "title": "Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.", "content": "In chloralose-anesthetized dogs, we investigated the disappearance of bradykinin on passage across the renal circulation. The peptide was infused into a renal artery at various doses (5-200 ng/kg min-1); renal blood flow and the concentration of kinins in renal venous blood were then determined and the percent survival of bradykinin on passage through the kidney calculated. Bradykinin caused a dose-related increase in renal blood flow, urine flow, sodium excretion, and kinin content of renal venous blood. Intravenous administration of BPP9alpha (300 mug/kg), a peptide kininase II inhibitor, potentiated the renal vasodilator, diuretic, and natriuretic actions of bradykinin and augmented the survival of the kinin on passage through the kidney from 12.72 +/- 1.64% in control dogs to 53.92 +/- 7.48% (P less than 0.001). Furthermore, the values of peptide survival were positively correlated with the increases in renal blood flow (r = 0.92, P less than 0.01), urine flow (r = 0.75, P less than 0.01), and sodium excretion (r = 0.68, P less than 0.01) produced by bradykinin. In addition, BPP9alpha by itself increased renal blood flow (16%, P less than 0.01), urine flow (115%, P less than 0.005), and sodium excretion (167%, P less than 0.02). Similarly, the concentration of kinin in renal venous blood and the excretion of urinary kinins rose from 0.11 +/- 0.03 ng/ml and 4.1 +/- 1.1 ng/min to 0.24 +/- 0.05 ng/ml (P less than 0.005) and 38.5 +/- 12.2 ng/min (P less than 0.02). These studies suggest that kinins generated intrarenally play a role in the regulation of renal blood flow and salt-water excretion and that variations in the capacity of the kidney to inactivate kinins may be a determinant of the intrarenal activity of the kallikrein-kinin system.", "contents": "Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition. In chloralose-anesthetized dogs, we investigated the disappearance of bradykinin on passage across the renal circulation. The peptide was infused into a renal artery at various doses (5-200 ng/kg min-1); renal blood flow and the concentration of kinins in renal venous blood were then determined and the percent survival of bradykinin on passage through the kidney calculated. Bradykinin caused a dose-related increase in renal blood flow, urine flow, sodium excretion, and kinin content of renal venous blood. Intravenous administration of BPP9alpha (300 mug/kg), a peptide kininase II inhibitor, potentiated the renal vasodilator, diuretic, and natriuretic actions of bradykinin and augmented the survival of the kinin on passage through the kidney from 12.72 +/- 1.64% in control dogs to 53.92 +/- 7.48% (P less than 0.001). Furthermore, the values of peptide survival were positively correlated with the increases in renal blood flow (r = 0.92, P less than 0.01), urine flow (r = 0.75, P less than 0.01), and sodium excretion (r = 0.68, P less than 0.01) produced by bradykinin. In addition, BPP9alpha by itself increased renal blood flow (16%, P less than 0.01), urine flow (115%, P less than 0.005), and sodium excretion (167%, P less than 0.02). Similarly, the concentration of kinin in renal venous blood and the excretion of urinary kinins rose from 0.11 +/- 0.03 ng/ml and 4.1 +/- 1.1 ng/min to 0.24 +/- 0.05 ng/ml (P less than 0.005) and 38.5 +/- 12.2 ng/min (P less than 0.02). These studies suggest that kinins generated intrarenally play a role in the regulation of renal blood flow and salt-water excretion and that variations in the capacity of the kidney to inactivate kinins may be a determinant of the intrarenal activity of the kallikrein-kinin system."} {"id": "PMID:168000", "title": "Localization patterns of plasma apolipoproteins in human atherosclerotic lesions.", "content": "The localization patterns of human plasma lipoproteins and their respective apoproteins and of neutral lipid were determined in normal and atherosclerotic arteries. Specific antisera were prepared against plasma low-density lipoproteins(LDL) and their apoproteins (apoB), high-density lipoproteins(HDL) and one of their major apoproteins (apoA-I1, and apoC-III, which is a major apoprotein of very low-density lipoproteins (VLDL). Using immunofluorescence techniques, the various antigens were localized in arterial samples obtained at surgery or autopsy. The three apoproteins and neutral lipid were localized to the same tissue areas, namely, lipid core regions and certain connective tissue of atherosclerotic lesions, in 61% of the fibrous plaques and 48% of the fatty streaks examined. In marked contrast, none of the uninvolved arterial regions showed the presence of all four factors together. As controls, the localization of other serum proteins was also determined in these arteries using immunofluorescence techniques. Fibrinogen was associated with regions of maximum complementary localization of factors in 37% of the fibrous plaques and 64% of the fatty streaks. However, albumin was found in only 4-5% of these same regions. The present results suggest that not only LDL but also HDL and VLDL or their respective apoproteins as well as fibrinogen are specifically retained by certain tissue components of the atherosclerotic lesion.", "contents": "Localization patterns of plasma apolipoproteins in human atherosclerotic lesions. The localization patterns of human plasma lipoproteins and their respective apoproteins and of neutral lipid were determined in normal and atherosclerotic arteries. Specific antisera were prepared against plasma low-density lipoproteins(LDL) and their apoproteins (apoB), high-density lipoproteins(HDL) and one of their major apoproteins (apoA-I1, and apoC-III, which is a major apoprotein of very low-density lipoproteins (VLDL). Using immunofluorescence techniques, the various antigens were localized in arterial samples obtained at surgery or autopsy. The three apoproteins and neutral lipid were localized to the same tissue areas, namely, lipid core regions and certain connective tissue of atherosclerotic lesions, in 61% of the fibrous plaques and 48% of the fatty streaks examined. In marked contrast, none of the uninvolved arterial regions showed the presence of all four factors together. As controls, the localization of other serum proteins was also determined in these arteries using immunofluorescence techniques. Fibrinogen was associated with regions of maximum complementary localization of factors in 37% of the fibrous plaques and 64% of the fatty streaks. However, albumin was found in only 4-5% of these same regions. The present results suggest that not only LDL but also HDL and VLDL or their respective apoproteins as well as fibrinogen are specifically retained by certain tissue components of the atherosclerotic lesion."} {"id": "PMID:168001", "title": "Clinical conference: De subitaneis mortibus. XIII. Multifocal Purkinije cell tumors of the heart.", "content": "Multifocal Purkinje cell tumors were found in the heart of a nine-month-old black female infant who died with arrhythmias which had become progressively more frequent and severe until they were completely intractable. The Purkinje cell tumors were composed of exactly the same type of cells found in the left bundle branch and the right bundle branch, and they were also located in the expected region of the His bundle. In none of these locations were these Purkinje cells forming normal longitudinally oriented Purkinje fibers, however, and no such fibers were found anywhere in this heart. The cells of the tumors contained glycogen but not in excess of that normally expected to be present in Purkinje cells. No evidence for a generalized abnormality of glycogen metabolism or storage was present. Except for the Purkinje cells, the remaining myocardial cells of the heart were all normal. The fundamental fault appeared to be failure of the Purkinje cells to organize into the normal histological pattern which is characterized by longitudinally oriented Purkinje fibers. Instead, all the Purkinje cells were rounded or polygonal and generally aggregated together into small discrete nodules of varying size. Future cases of this nature deserve careful attention to the nature of their cardiac rhythm and conduction, and in fatal cases there should be special studies of the histological appearance of their cardiac centers of impulse formation and conduction.", "contents": "Clinical conference: De subitaneis mortibus. XIII. Multifocal Purkinije cell tumors of the heart. Multifocal Purkinje cell tumors were found in the heart of a nine-month-old black female infant who died with arrhythmias which had become progressively more frequent and severe until they were completely intractable. The Purkinje cell tumors were composed of exactly the same type of cells found in the left bundle branch and the right bundle branch, and they were also located in the expected region of the His bundle. In none of these locations were these Purkinje cells forming normal longitudinally oriented Purkinje fibers, however, and no such fibers were found anywhere in this heart. The cells of the tumors contained glycogen but not in excess of that normally expected to be present in Purkinje cells. No evidence for a generalized abnormality of glycogen metabolism or storage was present. Except for the Purkinje cells, the remaining myocardial cells of the heart were all normal. The fundamental fault appeared to be failure of the Purkinje cells to organize into the normal histological pattern which is characterized by longitudinally oriented Purkinje fibers. Instead, all the Purkinje cells were rounded or polygonal and generally aggregated together into small discrete nodules of varying size. Future cases of this nature deserve careful attention to the nature of their cardiac rhythm and conduction, and in fatal cases there should be special studies of the histological appearance of their cardiac centers of impulse formation and conduction."} {"id": "PMID:168002", "title": "Potential for clinical use of the analytical laser microprobe for element measurement.", "content": "Use of the laser microprobe for rapid emission spectroscopic analysis of elements in microscopic samples of biological material is described. The technique depends on vaporization of the microsample with a focused laser beam at a temperature that renders the vapor incandescent for spectrochemical analysis. Spectral line intensities are recorded photographically with densitometry of the negatives or photoelectrically. Current capability permits analysis of about 10(-8) to 10(-10) g of tissue, with detection limits of 10-12 to 10-15 g of element. Groups of elements can be simultaneously analyzed. Minimum sample preparation is required, and the analysis is done on the stage of a light microscope, usually on an air-dried sample on a plastic slide. We exemplify the technique in analysis of gold in cultured fibroblasts treated with gold salts and in human skin after treatment with gold salts for rheumatoid arthritis, in element changes in biopsies of transplanted human hearts, and in unique profiles of groups of elements in human cancer tissue.", "contents": "Potential for clinical use of the analytical laser microprobe for element measurement. Use of the laser microprobe for rapid emission spectroscopic analysis of elements in microscopic samples of biological material is described. The technique depends on vaporization of the microsample with a focused laser beam at a temperature that renders the vapor incandescent for spectrochemical analysis. Spectral line intensities are recorded photographically with densitometry of the negatives or photoelectrically. Current capability permits analysis of about 10(-8) to 10(-10) g of tissue, with detection limits of 10-12 to 10-15 g of element. Groups of elements can be simultaneously analyzed. Minimum sample preparation is required, and the analysis is done on the stage of a light microscope, usually on an air-dried sample on a plastic slide. We exemplify the technique in analysis of gold in cultured fibroblasts treated with gold salts and in human skin after treatment with gold salts for rheumatoid arthritis, in element changes in biopsies of transplanted human hearts, and in unique profiles of groups of elements in human cancer tissue."} {"id": "PMID:168003", "title": "Application of electron spin resonance to determination of serum drug concentrations.", "content": "Displacement of spin-labeled drugs from drug-specific antibodies in human serum can be measured by use of electron spin resonance. This \"spin immunoassay\" has advantages of speed, simplicity, and small volume requirements over other standard techniques such as gas-liquid, liquid-liquid, or thin-layer chromatography. Unlike radioimmunoassay, there is no need to separate free and bound label and there are no radiation hazards. We present clinical and experimental data showing how this method can be applied to the routine determination of morphine and diphenylhydantoin concentrations in serum.", "contents": "Application of electron spin resonance to determination of serum drug concentrations. Displacement of spin-labeled drugs from drug-specific antibodies in human serum can be measured by use of electron spin resonance. This \"spin immunoassay\" has advantages of speed, simplicity, and small volume requirements over other standard techniques such as gas-liquid, liquid-liquid, or thin-layer chromatography. Unlike radioimmunoassay, there is no need to separate free and bound label and there are no radiation hazards. We present clinical and experimental data showing how this method can be applied to the routine determination of morphine and diphenylhydantoin concentrations in serum."} {"id": "PMID:168005", "title": "Evaluation of serum lipid and lipoprotein levels in normal Chinese. The influence of dietary habit, body weight, exercise and a familial record of coronary heart disease.", "content": "The effects of dietary habit, body weight, physical activity and a familial record of coronary heart disease on serum lipid and lipoprotein levels in Chinese were examined. Increased dietary preference for animal meat products was associated with increased serum cholesterol and beta-lipoprotein levels. Increased carbohydrate intake and overweight were associated with increased serum triglyceride and pre-beta-lipoprotein levels. A familial record of coronary heart disease was associated with increased serum total lipid and pre-beta-lipoprotein levels. Based on these results, the factors which influence the serum lipid and lipoprotein concentrations in Chinese are probably similar to those in other ethnic groups.", "contents": "Evaluation of serum lipid and lipoprotein levels in normal Chinese. The influence of dietary habit, body weight, exercise and a familial record of coronary heart disease. The effects of dietary habit, body weight, physical activity and a familial record of coronary heart disease on serum lipid and lipoprotein levels in Chinese were examined. Increased dietary preference for animal meat products was associated with increased serum cholesterol and beta-lipoprotein levels. Increased carbohydrate intake and overweight were associated with increased serum triglyceride and pre-beta-lipoprotein levels. A familial record of coronary heart disease was associated with increased serum total lipid and pre-beta-lipoprotein levels. Based on these results, the factors which influence the serum lipid and lipoprotein concentrations in Chinese are probably similar to those in other ethnic groups."} {"id": "PMID:168006", "title": "The effect of heparin on serum lipoprotein-X.", "content": "Serum lipoprotein-X was investigated in 12 patients with cholestasis in basal conditions and 20 minutes after intravenous heparin. In all cases, lipoprotein-X was positive in the first sample and became negative after heparin. A decrease in triglycerides was observed in all patients after heparin with an increase in free fatty acids and mobilization of prebetalipoproteins, and a transformation of lecithin into lysoleithin in 4 cases after heparin. These facts suggest that heparin plays an important role in the mobilization of serum lipoprotein-X.", "contents": "The effect of heparin on serum lipoprotein-X. Serum lipoprotein-X was investigated in 12 patients with cholestasis in basal conditions and 20 minutes after intravenous heparin. In all cases, lipoprotein-X was positive in the first sample and became negative after heparin. A decrease in triglycerides was observed in all patients after heparin with an increase in free fatty acids and mobilization of prebetalipoproteins, and a transformation of lecithin into lysoleithin in 4 cases after heparin. These facts suggest that heparin plays an important role in the mobilization of serum lipoprotein-X."} {"id": "PMID:168007", "title": "\"Sinking\" lipoprotein in normal, hyperlipoproteinaemic and atherosclerotic patients.", "content": "The presence of a \"sinking\" lipoprotein (SLP), demonstrated by combining electrophoretic and ultracentrifugal methods, has been recorded in 13.6% of 44 normal subjects, in 62.2% of 37 hyperlipoproteinaemic patients with types IIA, IIB and IV and in 39.8% of 107 atherosclerotic patients. The recorded data suggest that the \"sinking\" lipoprotein may be related to human atherosclerosis and to hyperipoproteinaemic states. A pre-beta (S band in the fraction with density greater than 1.006 appeared in 2 out of 20 subjects receiving as isocaloric hyperglucidic diet (CHO, 80; F, 5;P, 15) for 8 days and in 3 out of 10 subjects receiving an acute ethanol oral load. The nature of the nutritionally determined lipoprotein is doubtful. It seems improbable that the newly synthetized lipoprotein is the \"true\" sinking lipoprotein as this considered to be a genetically determined marker. These data may signify that other \"sinking\" lipoproteins unrelated to LP-Berg system may exist or may be determined. It is also probable that the new synthetized lipoprotein may have some relationship with the \"intermediate\" lipoprotein.", "contents": "\"Sinking\" lipoprotein in normal, hyperlipoproteinaemic and atherosclerotic patients. The presence of a \"sinking\" lipoprotein (SLP), demonstrated by combining electrophoretic and ultracentrifugal methods, has been recorded in 13.6% of 44 normal subjects, in 62.2% of 37 hyperlipoproteinaemic patients with types IIA, IIB and IV and in 39.8% of 107 atherosclerotic patients. The recorded data suggest that the \"sinking\" lipoprotein may be related to human atherosclerosis and to hyperipoproteinaemic states. A pre-beta (S band in the fraction with density greater than 1.006 appeared in 2 out of 20 subjects receiving as isocaloric hyperglucidic diet (CHO, 80; F, 5;P, 15) for 8 days and in 3 out of 10 subjects receiving an acute ethanol oral load. The nature of the nutritionally determined lipoprotein is doubtful. It seems improbable that the newly synthetized lipoprotein is the \"true\" sinking lipoprotein as this considered to be a genetically determined marker. These data may signify that other \"sinking\" lipoproteins unrelated to LP-Berg system may exist or may be determined. It is also probable that the new synthetized lipoprotein may have some relationship with the \"intermediate\" lipoprotein."} {"id": "PMID:168008", "title": "The biochemical composition and metabolism of lipoproteins in type V hyperlipoproteinaemia.", "content": "The biochemical composition of lipoproteins in Type V hyperlipoproteinaemia was investigated with special reference to apolipoprotein-B. The in vivo metabolism of protein-labelled low density lipoprotein was also studied in five such patients (3 diabetic, 2 obese subjects). In association with pathologically elevated plasma levels of chylomicrons and very low density lipoproteins, low density lipoprotein concentration was significantly reduced. The proportions of triglyceride to apo-B and triglyceride to cholesterol were significantly increased in all lipoprotein classes, while the proportion of cholesterol to apo-B was significantly reduced. Disappearance of chylomicronaemia with treatment was associated with a prompt increase in low density lipoprotein concentration. The reduced low density lipoprotein concentration was accompanied by an accelerated fractional turnover rate, and by an absolute turnover rate which was subnormal. These results were interpreted as reduced synthesis of low density lipoprotein apoprotein and as a possible block in the conversion of very low density lipoprotein to low density lipoprotein in some Type V patients.", "contents": "The biochemical composition and metabolism of lipoproteins in type V hyperlipoproteinaemia. The biochemical composition of lipoproteins in Type V hyperlipoproteinaemia was investigated with special reference to apolipoprotein-B. The in vivo metabolism of protein-labelled low density lipoprotein was also studied in five such patients (3 diabetic, 2 obese subjects). In association with pathologically elevated plasma levels of chylomicrons and very low density lipoproteins, low density lipoprotein concentration was significantly reduced. The proportions of triglyceride to apo-B and triglyceride to cholesterol were significantly increased in all lipoprotein classes, while the proportion of cholesterol to apo-B was significantly reduced. Disappearance of chylomicronaemia with treatment was associated with a prompt increase in low density lipoprotein concentration. The reduced low density lipoprotein concentration was accompanied by an accelerated fractional turnover rate, and by an absolute turnover rate which was subnormal. These results were interpreted as reduced synthesis of low density lipoprotein apoprotein and as a possible block in the conversion of very low density lipoprotein to low density lipoprotein in some Type V patients."} {"id": "PMID:168010", "title": "Isolation of Wilms' tumor antigens by chelation.", "content": "A procedure for ethylenediaminetetraacetate extraction of minced Wilm's tumor was assessed as a method for isolating Wilm's tumor antigens. An antigen was detected by immunodiffusion using an adsorbed antiserum to this extract. This antigen was also found in ethylenediaminetetraacetate extracts of in vitro cultures of nephroblastoma cells.", "contents": "Isolation of Wilms' tumor antigens by chelation. A procedure for ethylenediaminetetraacetate extraction of minced Wilm's tumor was assessed as a method for isolating Wilm's tumor antigens. An antigen was detected by immunodiffusion using an adsorbed antiserum to this extract. This antigen was also found in ethylenediaminetetraacetate extracts of in vitro cultures of nephroblastoma cells."} {"id": "PMID:168012", "title": "Plasma apolipoprotein A levels in healthy human adults.", "content": "The apolipoprotein A concentration in the plasma of ten healthy human subjects was measured immunologically on three occasions at monthly intervals and the following results recorded. 1. There was no difference between fasting and non-fasting apoprotein A concentrations. 2. Apoliportein A levels were higher in females than in males (p less than 0.001). 3. The correlation coefficient calculated for high density lipoprotein cholesterol and apolipoprotein A was 0.62. 4. The apoprotein values varied widely between subjects and ther were considerable concentration differences from month to month in the plasma of each individual.", "contents": "Plasma apolipoprotein A levels in healthy human adults. The apolipoprotein A concentration in the plasma of ten healthy human subjects was measured immunologically on three occasions at monthly intervals and the following results recorded. 1. There was no difference between fasting and non-fasting apoprotein A concentrations. 2. Apoliportein A levels were higher in females than in males (p less than 0.001). 3. The correlation coefficient calculated for high density lipoprotein cholesterol and apolipoprotein A was 0.62. 4. The apoprotein values varied widely between subjects and ther were considerable concentration differences from month to month in the plasma of each individual."} {"id": "PMID:168013", "title": "Serum levels of thyroid-stimulating hormone in hyperlipoproteinemia.", "content": "Similar serum lipoprotein abnormalities have been demonstrated in hyperlipoproteinemia type III and hypothyroidism. In this study the levels of thyroid-stimulating hormone in serum were determined in clinically euthyroid patients with different types of hyperlipoproteinemias and in subjects with a normal lipoprotein pattern. The mean value for thyroid-stimulating hormone was significantly higher in the group with hyperlipoproteinemia type III than in normal controls (p smaller than 0.01) and in the group with hyperlipoproteinemia type II A (p smaller than 0.02). The levels of thyroid-stimulating hormone were positively correlated to the triglyceride and cholesterol concentration in the very low density lipoprotein fraction and the \"\"III-index''.", "contents": "Serum levels of thyroid-stimulating hormone in hyperlipoproteinemia. Similar serum lipoprotein abnormalities have been demonstrated in hyperlipoproteinemia type III and hypothyroidism. In this study the levels of thyroid-stimulating hormone in serum were determined in clinically euthyroid patients with different types of hyperlipoproteinemias and in subjects with a normal lipoprotein pattern. The mean value for thyroid-stimulating hormone was significantly higher in the group with hyperlipoproteinemia type III than in normal controls (p smaller than 0.01) and in the group with hyperlipoproteinemia type II A (p smaller than 0.02). The levels of thyroid-stimulating hormone were positively correlated to the triglyceride and cholesterol concentration in the very low density lipoprotein fraction and the \"\"III-index''."} {"id": "PMID:168022", "title": "A dominant syndrome of metacarpal and metatarsal asymmetry with tarsal and carpal fusions, syndactyly, articular dysplasia and platyspondyly.", "content": "A mother and daughter with metacarpal and metatarsal asymmetry, tarsal and carpal fusions, long bone articular dysplasia and platyspondyly are reported as a possible autosomal dominant syndrome affecting skeletal development. The asymmetry of the second metacarpals is perhaps the most striking finding and resulted in a range of bone lengths in the two individuals from minus 6.3 to plus 3.7 standard deviations from the mean.", "contents": "A dominant syndrome of metacarpal and metatarsal asymmetry with tarsal and carpal fusions, syndactyly, articular dysplasia and platyspondyly. A mother and daughter with metacarpal and metatarsal asymmetry, tarsal and carpal fusions, long bone articular dysplasia and platyspondyly are reported as a possible autosomal dominant syndrome affecting skeletal development. The asymmetry of the second metacarpals is perhaps the most striking finding and resulted in a range of bone lengths in the two individuals from minus 6.3 to plus 3.7 standard deviations from the mean."} {"id": "PMID:168025", "title": "The value of the external carotid circulation in the assessment of intracranial disease.", "content": "The external carotid circulation often contributes a vascular supply in intracranial disease. Adequate radiological evaluation of this circulation is important and may alter the surgical management in these patients.", "contents": "The value of the external carotid circulation in the assessment of intracranial disease. The external carotid circulation often contributes a vascular supply in intracranial disease. Adequate radiological evaluation of this circulation is important and may alter the surgical management in these patients."} {"id": "PMID:168026", "title": "Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells.", "content": "1. Intracellular K+ content, water spaces and corticosterone output were measured in isolated zona glomerulosa and zona fasciculata-reticularis cell suspensions of rat adrenal cortex, after incubation in vitro under conditions designed to alter steroidogenesis. 2. Intracellular K+ of unpurified zona glomerulosa cells was not altered after stimulation of corticosterone output with serotonin. Similarly, with zona glomerulosa cells purified by unit gravity sedimentation, no change in intracellular K+ was detected after stimulation of steroidogenesis with serotonin or angiotensin II. 3. In high-potassium medium (final concentration 8.4 mmol/1), parallel increases in intracellular K+ and corticosterone output were observed with both purified zona glomerulosa cells. However, a similar increase in intracellular K+ also occurred in high-potassium medium with zona fasciculata cells, whose steroid output is unresponsive to external potassium concentration ([K+]). 4. Ouabain at 10(-5) mol/1 depressed the intracellular [K+] of glomerulosa cells but did not alter basal or stimulated corticosterone output. Similar results were obtained with fasciculata cells. 5. Ouabain at 5 times 10(-4) mol/1 further depressed intracellular [K-+] of glomerulosa cells and inhibited basal and stimulated corticosterone output. However, this concentration of ouabain also inhibited steroidogenesis in fasciculata cells. 6. These results demonstrate a variety of situations where changes in intracellular [K+] are dissociated from those in corticosterone output and indicate that intracellular [K+] cannot be the sole mechanism regulating steroidogenesis under these conditions.", "contents": "Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells. 1. Intracellular K+ content, water spaces and corticosterone output were measured in isolated zona glomerulosa and zona fasciculata-reticularis cell suspensions of rat adrenal cortex, after incubation in vitro under conditions designed to alter steroidogenesis. 2. Intracellular K+ of unpurified zona glomerulosa cells was not altered after stimulation of corticosterone output with serotonin. Similarly, with zona glomerulosa cells purified by unit gravity sedimentation, no change in intracellular K+ was detected after stimulation of steroidogenesis with serotonin or angiotensin II. 3. In high-potassium medium (final concentration 8.4 mmol/1), parallel increases in intracellular K+ and corticosterone output were observed with both purified zona glomerulosa cells. However, a similar increase in intracellular K+ also occurred in high-potassium medium with zona fasciculata cells, whose steroid output is unresponsive to external potassium concentration ([K+]). 4. Ouabain at 10(-5) mol/1 depressed the intracellular [K+] of glomerulosa cells but did not alter basal or stimulated corticosterone output. Similar results were obtained with fasciculata cells. 5. Ouabain at 5 times 10(-4) mol/1 further depressed intracellular [K-+] of glomerulosa cells and inhibited basal and stimulated corticosterone output. However, this concentration of ouabain also inhibited steroidogenesis in fasciculata cells. 6. These results demonstrate a variety of situations where changes in intracellular [K+] are dissociated from those in corticosterone output and indicate that intracellular [K+] cannot be the sole mechanism regulating steroidogenesis under these conditions."} {"id": "PMID:168027", "title": "Mobilizing in response to a major disaster.", "content": "In an attempt to meet the emergency needs of a major disaster in what some have termed \"the greatest natural disaster in American history,\" the National Institute of Mental Health (NIMH) responded immediately by dispatching a mental health team to Wilkes Barre, Pennsylvania, to examine and deal with the mental health needs of flood survivors. After conferring with local mental health workers and rescue officials, the team concluded that there would be long-term psychiatric sequelae of the flood and that NIMH would have a useful and important role in dealing with them. The team made its report to the Director of NIMH, Dr. Bertram S. Brown, who then assigned his executive assistant, K. Patrick Okura, the task of fleshing out the present mental health program of the area and finding out how NIMH resources could best be put to use in meeting the crisis. The NIMH program, in keeping with its tradition, consisted of three parts: service, training, and evaluation. Within a 30-day period a proposal requesting frunds for a year-long program of mental health services to the residents of the flood-affected area was approved and launched. This article describes \"Operation Outreach,\" as the program was called.", "contents": "Mobilizing in response to a major disaster. In an attempt to meet the emergency needs of a major disaster in what some have termed \"the greatest natural disaster in American history,\" the National Institute of Mental Health (NIMH) responded immediately by dispatching a mental health team to Wilkes Barre, Pennsylvania, to examine and deal with the mental health needs of flood survivors. After conferring with local mental health workers and rescue officials, the team concluded that there would be long-term psychiatric sequelae of the flood and that NIMH would have a useful and important role in dealing with them. The team made its report to the Director of NIMH, Dr. Bertram S. Brown, who then assigned his executive assistant, K. Patrick Okura, the task of fleshing out the present mental health program of the area and finding out how NIMH resources could best be put to use in meeting the crisis. The NIMH program, in keeping with its tradition, consisted of three parts: service, training, and evaluation. Within a 30-day period a proposal requesting frunds for a year-long program of mental health services to the residents of the flood-affected area was approved and launched. This article describes \"Operation Outreach,\" as the program was called."} {"id": "PMID:168023", "title": "Stimulation by angiotensin II of the release of vasopressin from incubated rat neurohypophyses---possible involvement of cyclic AMP.", "content": "1. Calcium did not influence the spontaneous release of vasopressin from rat neurohypophyses in vitro when used in concentrations of 0.05, 0.5 and 2.8 mM in the bathing medium. 2. Stimulation of the basal output of vasopressin by angiotensin II (1 X 10(-9) M) required at least 0.5 mM calcium in the medium. 3. Angiotensin II stimulated the release of vasopressin within 2.5 min of incubation, maximal release was observed after 10 min. 4. Angiotensin II rapidly promoted the accumulation of tissue cyclic AMP; maximal accumulation was observed after 5 min of incubation. 5. Theophylline and dibutyryl cyclic AMP produced varying degree of stimulation of the release of vasopressin. 6. Increases in vasopressin secretion and in the accumulation of cyclic AMP were always present when neurohypophyses were exposed to optiman concentrations of angiotensin II. The results presented suggested that cyclic AMP may be an intermediate step for the release of vasopressin by endogenous angiotensin II.", "contents": "Stimulation by angiotensin II of the release of vasopressin from incubated rat neurohypophyses---possible involvement of cyclic AMP. 1. Calcium did not influence the spontaneous release of vasopressin from rat neurohypophyses in vitro when used in concentrations of 0.05, 0.5 and 2.8 mM in the bathing medium. 2. Stimulation of the basal output of vasopressin by angiotensin II (1 X 10(-9) M) required at least 0.5 mM calcium in the medium. 3. Angiotensin II stimulated the release of vasopressin within 2.5 min of incubation, maximal release was observed after 10 min. 4. Angiotensin II rapidly promoted the accumulation of tissue cyclic AMP; maximal accumulation was observed after 5 min of incubation. 5. Theophylline and dibutyryl cyclic AMP produced varying degree of stimulation of the release of vasopressin. 6. Increases in vasopressin secretion and in the accumulation of cyclic AMP were always present when neurohypophyses were exposed to optiman concentrations of angiotensin II. The results presented suggested that cyclic AMP may be an intermediate step for the release of vasopressin by endogenous angiotensin II."} {"id": "PMID:168024", "title": "Structural requirements for angiotensin analogues to accumulate cyclic AMP and release vasopressin from the incubated rat neurohypophysis.", "content": "1. Angiotensin I, a decapeptide, stimulated the accumulation of cyclic 3',5'-AMP (cyclic AMP) and the release of vasopressin from incubated rat neurohypophyses. 2. Various octapeptides related to angiotensin II were capable of producing similar neurohypophyseal effects. 3. Longer incubation periods were needed with peptides having alterations or omission (e.g. heptapeptide 2-8) at position 1 of the parent molecule to evoke similar effects to those of angiotensin II. 4. Our results suggest strongly that physiological doses of angiotensin-related molecules stimulate the secretion of vasopressin through cyclic AMP, and that the neurohypophyseal receptor responsible for these effects is similar to that involved in their peripheral actions.", "contents": "Structural requirements for angiotensin analogues to accumulate cyclic AMP and release vasopressin from the incubated rat neurohypophysis. 1. Angiotensin I, a decapeptide, stimulated the accumulation of cyclic 3',5'-AMP (cyclic AMP) and the release of vasopressin from incubated rat neurohypophyses. 2. Various octapeptides related to angiotensin II were capable of producing similar neurohypophyseal effects. 3. Longer incubation periods were needed with peptides having alterations or omission (e.g. heptapeptide 2-8) at position 1 of the parent molecule to evoke similar effects to those of angiotensin II. 4. Our results suggest strongly that physiological doses of angiotensin-related molecules stimulate the secretion of vasopressin through cyclic AMP, and that the neurohypophyseal receptor responsible for these effects is similar to that involved in their peripheral actions."} {"id": "PMID:168031", "title": "Complete Kl\u00fcver-Bucy syndrome in man.", "content": "A 22 year old right-handed man suffered a viral meningoencephalitis, possibly herpetic, resulting in bilateral damage to the temporal lobes as confirmed by appropriate clinical, electrophysiological and neuroradiological studies. Extended clinical neuropsychological evaluation documented all the characteristic features of the syndrome described by Kl\u00fcver and Bucy following bilateral ablation of the temporal lobes in adult Rhesus monkeys, including \"psychic blindness,\" oral exploration, hypermetamorphic impulse to action,\" lack of emotional responsiveness, aberrant sexual behavior, and an insatiable appetite. Additionally, a severe Wernicke's aphasia and a profound memory disorder were evident. The significance of these features as regards limbic function in the human is discussed.", "contents": "Complete Kl\u00fcver-Bucy syndrome in man. A 22 year old right-handed man suffered a viral meningoencephalitis, possibly herpetic, resulting in bilateral damage to the temporal lobes as confirmed by appropriate clinical, electrophysiological and neuroradiological studies. Extended clinical neuropsychological evaluation documented all the characteristic features of the syndrome described by Kl\u00fcver and Bucy following bilateral ablation of the temporal lobes in adult Rhesus monkeys, including \"psychic blindness,\" oral exploration, hypermetamorphic impulse to action,\" lack of emotional responsiveness, aberrant sexual behavior, and an insatiable appetite. Additionally, a severe Wernicke's aphasia and a profound memory disorder were evident. The significance of these features as regards limbic function in the human is discussed."} {"id": "PMID:168032", "title": "Multinuclide evaluation of hepatic mass lesions.", "content": "Radionuclide imaging with labeled colloids is widely used to evaluate and localize primary and metastatic tumors of the liver. The method is fairly sensitive, but the nonspecificity of focal defects remains a significant limitation. Lesions such as cysts and abscesses appear as space occupying areas that are indistinguishable from neoplastic masses. Utilizing a variety of radiopharmaceuticals, one may obtain additional information concerning such lesions. Hepatic blood flow scintiphotography is performed with the Anger camera following the intravenous injection of a high activity, small volume bolus of 99m-Tc pertechnetate. Vascular lesions such as hepatomas or hemangiomas will show increased activity in the lesion which should easily differentiate them from avascular processes such as abscesses, cirrhotic pseudomasses and most metastatic lesions, all of which remain \"cold\" on these flow studies. If one does not posses a camera, useful blood pool rectilinear scans of these lesions may be obtained with 131-I or 99m-Tc human serum albumin or ionic 113m-In. Additional information concerning the metabolic activity of focal defects on the colloid study is obtained using 75-Se-selenomethionine or 67-Ga. The former is an indicator of active protein metabolism while the latter attaches to lysozymes of metabolically active cells. With either agent, hepatomas show avid uptake, metastatic lesions show variable uptake, and cysts or chronic pseudotumors of cirrhosis show poor uptake. The two agents differ in abscess detection where 75-Se-selenomethionine uptake is poor while 67-Ga concentration generally is intense. 131-I-Rose Bengal occasionally may prove useful in demonstrating impression by an atypically positioned gallbladder or focal dilatation of the biliary tract as a cause of a defect on the colloid scan. Ultrasound examination may complement the radionuclide studies. It is useful for corroborating the presence of lesions and for evaluating their consistency (cystic vs. solid). The information obtained from this multinuclide approach has made scintigraphy examination of the livermore specific. After the completion of this non-invasive series of studies, one generally may venture an intelligent opinion concerning the etiology of the space occupying disease.", "contents": "Multinuclide evaluation of hepatic mass lesions. Radionuclide imaging with labeled colloids is widely used to evaluate and localize primary and metastatic tumors of the liver. The method is fairly sensitive, but the nonspecificity of focal defects remains a significant limitation. Lesions such as cysts and abscesses appear as space occupying areas that are indistinguishable from neoplastic masses. Utilizing a variety of radiopharmaceuticals, one may obtain additional information concerning such lesions. Hepatic blood flow scintiphotography is performed with the Anger camera following the intravenous injection of a high activity, small volume bolus of 99m-Tc pertechnetate. Vascular lesions such as hepatomas or hemangiomas will show increased activity in the lesion which should easily differentiate them from avascular processes such as abscesses, cirrhotic pseudomasses and most metastatic lesions, all of which remain \"cold\" on these flow studies. If one does not posses a camera, useful blood pool rectilinear scans of these lesions may be obtained with 131-I or 99m-Tc human serum albumin or ionic 113m-In. Additional information concerning the metabolic activity of focal defects on the colloid study is obtained using 75-Se-selenomethionine or 67-Ga. The former is an indicator of active protein metabolism while the latter attaches to lysozymes of metabolically active cells. With either agent, hepatomas show avid uptake, metastatic lesions show variable uptake, and cysts or chronic pseudotumors of cirrhosis show poor uptake. The two agents differ in abscess detection where 75-Se-selenomethionine uptake is poor while 67-Ga concentration generally is intense. 131-I-Rose Bengal occasionally may prove useful in demonstrating impression by an atypically positioned gallbladder or focal dilatation of the biliary tract as a cause of a defect on the colloid scan. Ultrasound examination may complement the radionuclide studies. It is useful for corroborating the presence of lesions and for evaluating their consistency (cystic vs. solid). The information obtained from this multinuclide approach has made scintigraphy examination of the livermore specific. After the completion of this non-invasive series of studies, one generally may venture an intelligent opinion concerning the etiology of the space occupying disease."} {"id": "PMID:168033", "title": "Critical review of tomography in radiology and nuclear medicine.", "content": "This review covers conventional radiographic tomography, radioisotopic tomography, and a review of computerized transaxial tomography. Simple, reproducible radiographic tomographic methods are increasing in use, and despite their complexity, the diagnostic results are superior to conventional radiographs. There are many different motions of the X-ray tube and the film which can be employed to create a tomogram. The perfect tomographic motion is partly determined by the geometric shape of the object to be imaged and the thickness of the plane of interest. The undirectional tomographic method blurs a point in a linear fashion; the pleuridirectional method blurs a point over a wider surface. Among the most popular directions used are linear, circular, elliptical, and hypocycloidal. The numerous applications of tomography described in this review are an encouraging, broad-based foundation from which the most clinically useful and economically feasible devices will emerge.", "contents": "Critical review of tomography in radiology and nuclear medicine. This review covers conventional radiographic tomography, radioisotopic tomography, and a review of computerized transaxial tomography. Simple, reproducible radiographic tomographic methods are increasing in use, and despite their complexity, the diagnostic results are superior to conventional radiographs. There are many different motions of the X-ray tube and the film which can be employed to create a tomogram. The perfect tomographic motion is partly determined by the geometric shape of the object to be imaged and the thickness of the plane of interest. The undirectional tomographic method blurs a point in a linear fashion; the pleuridirectional method blurs a point over a wider surface. Among the most popular directions used are linear, circular, elliptical, and hypocycloidal. The numerous applications of tomography described in this review are an encouraging, broad-based foundation from which the most clinically useful and economically feasible devices will emerge."} {"id": "PMID:168034", "title": "Comparison of 85Sr, 87mSr, 18F, and 99mTc-labeled phosphates for bone scanning.", "content": "The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents.", "contents": "Comparison of 85Sr, 87mSr, 18F, and 99mTc-labeled phosphates for bone scanning. The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents."} {"id": "PMID:168035", "title": "Biochemical anomalies of the nephrotic syndrome.", "content": "The nephrotic syndrome is the only hypoalbuminaemic state frequently associated with hyperlipidaemia. In the presence of a negative nitrogen balance, hyperlipidaemia is metabolically inappropriate and reflects the result of persistent breakaway from free fatty acid control. This lipid abnormality may result in the premature development of ischaemic heart disease in patients in whom it is not possible to control the primary renal abnormality. The authors suggest that future work should be directed towards thyroxine and insulin metabolism in nephrotic states.", "contents": "Biochemical anomalies of the nephrotic syndrome. The nephrotic syndrome is the only hypoalbuminaemic state frequently associated with hyperlipidaemia. In the presence of a negative nitrogen balance, hyperlipidaemia is metabolically inappropriate and reflects the result of persistent breakaway from free fatty acid control. This lipid abnormality may result in the premature development of ischaemic heart disease in patients in whom it is not possible to control the primary renal abnormality. The authors suggest that future work should be directed towards thyroxine and insulin metabolism in nephrotic states."} {"id": "PMID:168036", "title": "Diagnostic fiberoptic bronchoscopy: Techniques and results of biopsy in 600 patients.", "content": "Six hundred patients underwent diagnostic flexible fiberoptic bronchoscopy (FFB). The two diseases most frequently encountered were bronchogenic carcinoma in 330 patients (55 percent) and bacterial infection in 94 (16 percent). A positive cytology on biopsy material was obtained in 279 of 330 patients (85 percent) with primary lung cancer. Fluoroscopy was a valuable aid in diagnosing bronchogenic carcinoma, since 42 percent of the tumors were not visible endoscopically and required fluoroscopic control for placement of the biopsy instrument. Of the 55 patients with hemoptysis and negative chest x-ray films, nine (15 percent) had fiberoptically visible endobronchial carcinomas! In addition, two patients with carcinoma of the larynx and one with carcinoma of the nasopharynx were discovered. Transbronchial biopsy (TBB) in 68 patinets with diffuse and localized disease achieved an overall 69 percent diagnostic success, including a correct diagnosis in each of four patients with Pneumocystis carinii pneumonia. Brush biopsy provided additional valuable laboratory data in bacterial, mycobacterial and cytomegalovirsu infectious but had a poor yield in Pneumocystis infection. Complications as a result of forceps biopsy were minimal, except for brisk bleeding in six patients.", "contents": "Diagnostic fiberoptic bronchoscopy: Techniques and results of biopsy in 600 patients. Six hundred patients underwent diagnostic flexible fiberoptic bronchoscopy (FFB). The two diseases most frequently encountered were bronchogenic carcinoma in 330 patients (55 percent) and bacterial infection in 94 (16 percent). A positive cytology on biopsy material was obtained in 279 of 330 patients (85 percent) with primary lung cancer. Fluoroscopy was a valuable aid in diagnosing bronchogenic carcinoma, since 42 percent of the tumors were not visible endoscopically and required fluoroscopic control for placement of the biopsy instrument. Of the 55 patients with hemoptysis and negative chest x-ray films, nine (15 percent) had fiberoptically visible endobronchial carcinomas! In addition, two patients with carcinoma of the larynx and one with carcinoma of the nasopharynx were discovered. Transbronchial biopsy (TBB) in 68 patinets with diffuse and localized disease achieved an overall 69 percent diagnostic success, including a correct diagnosis in each of four patients with Pneumocystis carinii pneumonia. Brush biopsy provided additional valuable laboratory data in bacterial, mycobacterial and cytomegalovirsu infectious but had a poor yield in Pneumocystis infection. Complications as a result of forceps biopsy were minimal, except for brisk bleeding in six patients."} {"id": "PMID:168037", "title": "Myocardial and plasma levels of adenosine 3':5'-cyclic phosphate. Studies in experimental myocardial ischemia.", "content": "Alterations in myocardial and plasma levels of adenosine 3':5'-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic APM levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.", "contents": "Myocardial and plasma levels of adenosine 3':5'-cyclic phosphate. Studies in experimental myocardial ischemia. Alterations in myocardial and plasma levels of adenosine 3':5'-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic APM levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions."} {"id": "PMID:168038", "title": "The current status of prostaglandins and the lungs.", "content": "The prostaglandins are a group of pharmacologically potent lipid compounds whose role in pulmonary pathophysiology remains to be defined. There is not question that these compounds can induce constriction (PGF) or relaxation (PGE) of the smooth muscle in bronchi and pulmonary vessels. There is no question that the lungs are a major site of both the synthesis and degradation. These facts make speculation about the role of the prostaglandins in pulmonary disorders a tempting exercise. However, the current paucity of clinical data prevents any valid assessment of such speculation at this time and emphasizes the need for continued investigation of the role of prostaglandins in patients with lung disease.", "contents": "The current status of prostaglandins and the lungs. The prostaglandins are a group of pharmacologically potent lipid compounds whose role in pulmonary pathophysiology remains to be defined. There is not question that these compounds can induce constriction (PGF) or relaxation (PGE) of the smooth muscle in bronchi and pulmonary vessels. There is no question that the lungs are a major site of both the synthesis and degradation. These facts make speculation about the role of the prostaglandins in pulmonary disorders a tempting exercise. However, the current paucity of clinical data prevents any valid assessment of such speculation at this time and emphasizes the need for continued investigation of the role of prostaglandins in patients with lung disease."} {"id": "PMID:168039", "title": "Asymptomatic pulmonary granular cell tumor presenting as a coin lesion.", "content": "Granular cell tumor is a rare, usually benign neoplasm of neurogenic origin first described in 1926. Only 46 lesions, including the present case, of the 500 reported cases of this tumor, originated within the tracheobronchial tree. The case reported here is distinctly unusual because of its asymptomatic presentation as a coin lesion on chest roentgenogram. Electron microscopic examination of the tumor is presented.", "contents": "Asymptomatic pulmonary granular cell tumor presenting as a coin lesion. Granular cell tumor is a rare, usually benign neoplasm of neurogenic origin first described in 1926. Only 46 lesions, including the present case, of the 500 reported cases of this tumor, originated within the tracheobronchial tree. The case reported here is distinctly unusual because of its asymptomatic presentation as a coin lesion on chest roentgenogram. Electron microscopic examination of the tumor is presented."} {"id": "PMID:168040", "title": "Antibacterial activity of tobramycin against gram-negative bacteria and the combination of ampicillin/tobramycin against E. coli.", "content": "The antibacterial activity of tobramycin, gentamicin, erythromycin, cloxacillin, kanamycin, cephalexin, penicillin, carbenicillin and polymyxin were compared against 303 clinical bacterial isolates from a pediatric hospital patient population. Standard disk diffusion and agar-dilution methods were employed. Significant activity was demonstrated for tobramycin against pseudomonas, Klebsiella, Escherichia coli and both Staphylococcus aureus and albus; Tobramycin was significantly more active against Pseudomonas than gentamicin or the other antibiotics testedmcomparable activity to gentamicin was present for the other types of bacteria; Cross-resistance was not encountered between tobramycin and gentamicin. 30 isolates of E. coli were tested against the combination of tobramycin and ampicillin by the growth-curve method. Synergism was demonstrated in 4 isolates, antagonism in 1 and an additive effect in 25. A bactericidal effect was present at 24h against 17 isolates with tobramycin alone and against 25 isolates when combined with ampicillin. These results provide in vitro rationale for the consideration of tobramycin for clinical use in patients with Psuedomonas infections for the combination of ampicillin and tobramycin for the treatment of selected E.coli infections.", "contents": "Antibacterial activity of tobramycin against gram-negative bacteria and the combination of ampicillin/tobramycin against E. coli. The antibacterial activity of tobramycin, gentamicin, erythromycin, cloxacillin, kanamycin, cephalexin, penicillin, carbenicillin and polymyxin were compared against 303 clinical bacterial isolates from a pediatric hospital patient population. Standard disk diffusion and agar-dilution methods were employed. Significant activity was demonstrated for tobramycin against pseudomonas, Klebsiella, Escherichia coli and both Staphylococcus aureus and albus; Tobramycin was significantly more active against Pseudomonas than gentamicin or the other antibiotics testedmcomparable activity to gentamicin was present for the other types of bacteria; Cross-resistance was not encountered between tobramycin and gentamicin. 30 isolates of E. coli were tested against the combination of tobramycin and ampicillin by the growth-curve method. Synergism was demonstrated in 4 isolates, antagonism in 1 and an additive effect in 25. A bactericidal effect was present at 24h against 17 isolates with tobramycin alone and against 25 isolates when combined with ampicillin. These results provide in vitro rationale for the consideration of tobramycin for clinical use in patients with Psuedomonas infections for the combination of ampicillin and tobramycin for the treatment of selected E.coli infections."} {"id": "PMID:168042", "title": "[Verner-Morrison syndrome].", "content": "Based on one case the Verner-Morrison-syndrome is demonstrated and discussed in detail. Clinically profuse watery diarrhea and severe hypokalemia are predominant. The pathogenesis is not quite clear. Curative therapy consists in radical surgical removal of the endocrinologically active tumores or diffuse hyperplasia.", "contents": "[Verner-Morrison syndrome]. Based on one case the Verner-Morrison-syndrome is demonstrated and discussed in detail. Clinically profuse watery diarrhea and severe hypokalemia are predominant. The pathogenesis is not quite clear. Curative therapy consists in radical surgical removal of the endocrinologically active tumores or diffuse hyperplasia."} {"id": "PMID:168043", "title": "Protein phosphorylation and metabolic control.", "content": "The regulation of enzyme activity through the phosphorylation and dephosphorylation of specific seryl or threonyl residues in enzymes is now recognized as an important control mechanism. A great many non-enzymic proteins may also be interconverted between phosphorylated and non-phosphorylated forms, but in these instances the function served by phosphorylation is not well understood. This lack of understanding is probably due to our lack of knowledge of the specialized actions of most non-enzymic proteins. The sequences of phosphorylation and dephosphorylation of proteins are, of necessity, subject to rigid control. If this were not so, the ATP supply of a cell would be rapidly depleted. Moreover, such processes must be regulated for metabolic interconversions to have a physiological regulatory role. For the best studied system, the interconversion of phosphorylase b and phosphorylase a, many different factors controlling the phosphorylation and dephosphorylation steps have been elucidated. Probably this process is constrained so that it uses only a little energy. In this paper, these constraints are examined.", "contents": "Protein phosphorylation and metabolic control. The regulation of enzyme activity through the phosphorylation and dephosphorylation of specific seryl or threonyl residues in enzymes is now recognized as an important control mechanism. A great many non-enzymic proteins may also be interconverted between phosphorylated and non-phosphorylated forms, but in these instances the function served by phosphorylation is not well understood. This lack of understanding is probably due to our lack of knowledge of the specialized actions of most non-enzymic proteins. The sequences of phosphorylation and dephosphorylation of proteins are, of necessity, subject to rigid control. If this were not so, the ATP supply of a cell would be rapidly depleted. Moreover, such processes must be regulated for metabolic interconversions to have a physiological regulatory role. For the best studied system, the interconversion of phosphorylase b and phosphorylase a, many different factors controlling the phosphorylation and dephosphorylation steps have been elucidated. Probably this process is constrained so that it uses only a little energy. In this paper, these constraints are examined."} {"id": "PMID:168044", "title": "Energy utilization for control.", "content": "When, on addition of a suitable substrate, a chemical potential is applied to an enzymic process such as glycolysis or respiration, whether in solution or membrane-bound, all components of the process pass into a nonequilibrium state, which might be steady or non-steady and which produces the following phenomena: (1) The reactants of each enzymic reaction are displaced from their equilibrium concentration, and energy is dissipated; (2) Part of each enzyme is transferred to a transition state of its catalytic function as well as isosteric and allosteric controlling functions, displaying local and gross conformation changes, and a rate-controlling state is generated; (3) In cyclic portions of a process futile events and chemical interconversion may occur; (4) In self- and cross-coupled portions of a process, oscillation with periodic changes of states and spatial propagation as well as instabilities may be observed; (5) At each step of a process, depending on the rate of flux and the specific enzymic function, a varying proportion of the free energy changes--which are concentration-dependent and derived from the overall potential of the system-is contributed to the control of flux rates. This will be exemplified for enzymes of bioenergetic pathways.", "contents": "Energy utilization for control. When, on addition of a suitable substrate, a chemical potential is applied to an enzymic process such as glycolysis or respiration, whether in solution or membrane-bound, all components of the process pass into a nonequilibrium state, which might be steady or non-steady and which produces the following phenomena: (1) The reactants of each enzymic reaction are displaced from their equilibrium concentration, and energy is dissipated; (2) Part of each enzyme is transferred to a transition state of its catalytic function as well as isosteric and allosteric controlling functions, displaying local and gross conformation changes, and a rate-controlling state is generated; (3) In cyclic portions of a process futile events and chemical interconversion may occur; (4) In self- and cross-coupled portions of a process, oscillation with periodic changes of states and spatial propagation as well as instabilities may be observed; (5) At each step of a process, depending on the rate of flux and the specific enzymic function, a varying proportion of the free energy changes--which are concentration-dependent and derived from the overall potential of the system-is contributed to the control of flux rates. This will be exemplified for enzymes of bioenergetic pathways."} {"id": "PMID:168046", "title": "Magnetic resonance studies of specificity in binding and catalysis of phosphotransferases.", "content": "Two common characteristics of the active site structures of intermediate complexes formed in kinase reactions have been observed by magnetic resonance techniques. First, in creatine, arginine, adenylate and pyruvate kinases (EC2.73.2, 2.7.3.3, 2.7.4.3 and 2.7.1.40, respectively) water is progressively excluded and the structure at the active site is progressively immobilized as each reactant is successively added to the enzyme, as monitored by electron spin resonance (e.s.r) and the enhancement of the proton relaxation rate of water (PRR) due to paramagnetic manganese(II) probe. Significant, and often wide-spread, changes in the protein conformation accompanying successive additions of reaction components are shown with 1H n.m.r. studies of pyruvate kinase. The second characteristic is that, for the ternary enzyme-Mn-nucleotide complexes, two parameters, the e.s.r. spectrum and PRR enhancement values, fall within a range of 10% for all enzymes investigated, with the exception of bovine brain creatine kinase. These similarities suggest a homology in teriary structure at the active sites of these enzymes. An unsuspected aspect of substrate and cofactor specificity has been revealed by e.s.r. spectroscopy of the manganese(II) complexes of the transition-state analogue of creatine kinase (E-MnADP-formate-creatine) and of the ternary phosphoenolpyruvate complex. In the former case, replacement of ADP, the normal substrate, by its substrate analogues IDP or 2acute-deoxyadenosine diphosphate produced two interconvertible species of the transition-state analogue complexes, observed in the e.s.r. spectra as an isotropic species and a highly anisotropic species. With the normal substrate, only the anisotropic species is observed. Similarly, in the case of the complex pyruvate kinase-Mn-phosphoenolpyruvate, when the normal monovalent activator K+ is replaced by the inert tetramethylammonium ion, again two interconvertible species rather than the normal one species are observed by e.s.r. spectroscopy. The implications of these phenomena for the relation of specificity to catalytic efficiency are discussed.", "contents": "Magnetic resonance studies of specificity in binding and catalysis of phosphotransferases. Two common characteristics of the active site structures of intermediate complexes formed in kinase reactions have been observed by magnetic resonance techniques. First, in creatine, arginine, adenylate and pyruvate kinases (EC2.73.2, 2.7.3.3, 2.7.4.3 and 2.7.1.40, respectively) water is progressively excluded and the structure at the active site is progressively immobilized as each reactant is successively added to the enzyme, as monitored by electron spin resonance (e.s.r) and the enhancement of the proton relaxation rate of water (PRR) due to paramagnetic manganese(II) probe. Significant, and often wide-spread, changes in the protein conformation accompanying successive additions of reaction components are shown with 1H n.m.r. studies of pyruvate kinase. The second characteristic is that, for the ternary enzyme-Mn-nucleotide complexes, two parameters, the e.s.r. spectrum and PRR enhancement values, fall within a range of 10% for all enzymes investigated, with the exception of bovine brain creatine kinase. These similarities suggest a homology in teriary structure at the active sites of these enzymes. An unsuspected aspect of substrate and cofactor specificity has been revealed by e.s.r. spectroscopy of the manganese(II) complexes of the transition-state analogue of creatine kinase (E-MnADP-formate-creatine) and of the ternary phosphoenolpyruvate complex. In the former case, replacement of ADP, the normal substrate, by its substrate analogues IDP or 2acute-deoxyadenosine diphosphate produced two interconvertible species of the transition-state analogue complexes, observed in the e.s.r. spectra as an isotropic species and a highly anisotropic species. With the normal substrate, only the anisotropic species is observed. Similarly, in the case of the complex pyruvate kinase-Mn-phosphoenolpyruvate, when the normal monovalent activator K+ is replaced by the inert tetramethylammonium ion, again two interconvertible species rather than the normal one species are observed by e.s.r. spectroscopy. The implications of these phenomena for the relation of specificity to catalytic efficiency are discussed."} {"id": "PMID:168050", "title": "[Increased cAMP concentration in parotid secretion in arterial hypertension: relationship to plasma-renin activity (author's transl)].", "content": "Hypertensives with normal and increased plasma-renin activity have an increased salivary excretion of cyclic adenosine monophosphate (cAMP) such as can be obtained in normal persons by stimulation of beta-adrenergic fibres. Propanolol, as a beta-receptor blocker, reduces such increased cAMP levels in hypertensives to minimal levels. The results suggest that beta-receptors are stimulated in hypertensives with normal or increased renin activity.", "contents": "[Increased cAMP concentration in parotid secretion in arterial hypertension: relationship to plasma-renin activity (author's transl)]. Hypertensives with normal and increased plasma-renin activity have an increased salivary excretion of cyclic adenosine monophosphate (cAMP) such as can be obtained in normal persons by stimulation of beta-adrenergic fibres. Propanolol, as a beta-receptor blocker, reduces such increased cAMP levels in hypertensives to minimal levels. The results suggest that beta-receptors are stimulated in hypertensives with normal or increased renin activity."} {"id": "PMID:168051", "title": "[Acute polyneuropathy caused by diphenylhydantoin intoxication (author's transl)].", "content": "In a 34-year-old epileptic male who had been treated for more than ten years with an average of 300 mg diphenylhydantoin and 200-300 mg phenobarbitone daily severe status epilepticus occurred which could only be controlled with high doses of diphenylhydantoin and phenobarbitone intravenously. During this treatment a severe mainly motor polyneuropathy occurred acutely which was more pronounced in the distal parts of the legs, and cerebellar symptoms were noted at the same time. The neuropathy largely regressed during the following year whereas the cerebellar symptoms persisted. There is evidence for direct toxic damage of peripheral nerves due to diphenylhydantoin. Phenobarbitone in high doses inhibits degradation of diphenylhydantoin competively. In this patient it very likely contributed towards the development of sever intoxication leading to neurological defects.", "contents": "[Acute polyneuropathy caused by diphenylhydantoin intoxication (author's transl)]. In a 34-year-old epileptic male who had been treated for more than ten years with an average of 300 mg diphenylhydantoin and 200-300 mg phenobarbitone daily severe status epilepticus occurred which could only be controlled with high doses of diphenylhydantoin and phenobarbitone intravenously. During this treatment a severe mainly motor polyneuropathy occurred acutely which was more pronounced in the distal parts of the legs, and cerebellar symptoms were noted at the same time. The neuropathy largely regressed during the following year whereas the cerebellar symptoms persisted. There is evidence for direct toxic damage of peripheral nerves due to diphenylhydantoin. Phenobarbitone in high doses inhibits degradation of diphenylhydantoin competively. In this patient it very likely contributed towards the development of sever intoxication leading to neurological defects."} {"id": "PMID:168054", "title": "The physicochemical properties of the cytoplasmic androgen receptor in the kidneys of normal, carrier female (tfm/+) and androgen-insensitive (tfm/y) mice.", "content": "The physicochemical properties of the androgen-receptor complex in mouse kidney were determined. The sedimentation coefficient, 7.9S and Stokes radius of 82A, are compatible with an asymmetric protein [frictional ratio f/fo 1.98; axial ratio, assuming a prolate ellipsoid, 20] having a molecular weight of 270,000 daltons. The kidney receptor is a relatively acidic protein of esoelectric point (pI) 4.8 and readily precipitable with protamine sulfate or ammonium sulfate. Studies with protein-specific reagents suggest that both cysteine and tryptophan residues may be necessary for maintaining the functional configuration associated with androgen binding. The kidney receptor can promote the association of testosterone with purified DNA. These properties of the androgen receptor in mouse kidney are remarkably similar to those of male accessory sexual tissue. The receptor detected in carrier female mice (tfm/+ heterozygous for the gene for testicular feminization (tfm), has the same physical properties as that of normal mice. However, due to a decrease in receptor concentration, binding activity is only 69% that of normal. In cytosol from androgen-insensitive mice (tfm/+), a specific androgen receptor cannot be demonstrated by 5 different techniques.", "contents": "The physicochemical properties of the cytoplasmic androgen receptor in the kidneys of normal, carrier female (tfm/+) and androgen-insensitive (tfm/y) mice. The physicochemical properties of the androgen-receptor complex in mouse kidney were determined. The sedimentation coefficient, 7.9S and Stokes radius of 82A, are compatible with an asymmetric protein [frictional ratio f/fo 1.98; axial ratio, assuming a prolate ellipsoid, 20] having a molecular weight of 270,000 daltons. The kidney receptor is a relatively acidic protein of esoelectric point (pI) 4.8 and readily precipitable with protamine sulfate or ammonium sulfate. Studies with protein-specific reagents suggest that both cysteine and tryptophan residues may be necessary for maintaining the functional configuration associated with androgen binding. The kidney receptor can promote the association of testosterone with purified DNA. These properties of the androgen receptor in mouse kidney are remarkably similar to those of male accessory sexual tissue. The receptor detected in carrier female mice (tfm/+ heterozygous for the gene for testicular feminization (tfm), has the same physical properties as that of normal mice. However, due to a decrease in receptor concentration, binding activity is only 69% that of normal. In cytosol from androgen-insensitive mice (tfm/+), a specific androgen receptor cannot be demonstrated by 5 different techniques."} {"id": "PMID:168055", "title": "Guanidination of ovine luteinizing hormone and effects on activity.", "content": "The free amino groups in oLH, oLHalpha and oLHbeta were guanidinated by O-methylisourea. The epsilon-NH2 groups of lysine residues reacted bo substitute these positions in the sequence with the more basic homoarginine residue. The alpha-NH2 groups did not react under the conditions used. Guanidinated oLH or the products of guanidinated oLHalpha + native oLHbeta or guanidinated oLHalpha + guanidinated oLHbeta were inactive in two bioassay systems. Native oLHalpha + guanidinated oLHbeta, however, showed potencies of 39% to 55% of that observed with the native subunit recombinant or native oLH. Possible structural implications for hormone-receptor site interactions are discussed.", "contents": "Guanidination of ovine luteinizing hormone and effects on activity. The free amino groups in oLH, oLHalpha and oLHbeta were guanidinated by O-methylisourea. The epsilon-NH2 groups of lysine residues reacted bo substitute these positions in the sequence with the more basic homoarginine residue. The alpha-NH2 groups did not react under the conditions used. Guanidinated oLH or the products of guanidinated oLHalpha + native oLHbeta or guanidinated oLHalpha + guanidinated oLHbeta were inactive in two bioassay systems. Native oLHalpha + guanidinated oLHbeta, however, showed potencies of 39% to 55% of that observed with the native subunit recombinant or native oLH. Possible structural implications for hormone-receptor site interactions are discussed."} {"id": "PMID:168056", "title": "Adrenal cells in tissue culture the effects of choleragen and ACTH on steroid and cyclic-AMP metabolism.", "content": "Primary cultures of mouse adrenocortical tumors provide a sensitive system for investigating the effects of the enterotoxin of the V. cholerae (choleragen) on cyclic-AMP metabolism in the intact cell. Like ACTH, the toxin stimulates the synthesis and release of steroids from these cells but its mode of action differs from that of ACTH. The steroidogenic response to ACTH is immediate and of limited duration. The initial rate of steroidogenesis is the highest. In contrast, the steroidogenic response to choleragen is preceded by a 30-240 minute lag period which is inversely related to the concentration of the toxin. Whereas prolongation of the response to a single dose of ACTH requires hormone concentrations above those producing maximal initial steroidogenic activity, persistent steroidogenesis is induced at all levels of the toxin. Steroidogenic responses are detectable with 10 pg/ml of choleragen or less. The respective effects of ACTH and choleragen on cyclic-AMP synthesis and release into the medium parallel those on steroidogenesis. Intracellular cyclic-AMP levels in ACTH-treated cells reach a peak within 20-30 minutes and decline to normal levels within 2-4 hours. In choleragen-treated cells, after the lage period, the levels of intracellular cyclic-AMP remain above control levels indefinitely. The effects of ACTH and choleragen on cyclic-AMP biosynthesis are additive at all levels of the two compounds. The effects of choleragen are blocked by prior treatment of the toxin with a five-fold molar excess of ganglioside GM1, a presumed constituent of the toxin-binding site.", "contents": "Adrenal cells in tissue culture the effects of choleragen and ACTH on steroid and cyclic-AMP metabolism. Primary cultures of mouse adrenocortical tumors provide a sensitive system for investigating the effects of the enterotoxin of the V. cholerae (choleragen) on cyclic-AMP metabolism in the intact cell. Like ACTH, the toxin stimulates the synthesis and release of steroids from these cells but its mode of action differs from that of ACTH. The steroidogenic response to ACTH is immediate and of limited duration. The initial rate of steroidogenesis is the highest. In contrast, the steroidogenic response to choleragen is preceded by a 30-240 minute lag period which is inversely related to the concentration of the toxin. Whereas prolongation of the response to a single dose of ACTH requires hormone concentrations above those producing maximal initial steroidogenic activity, persistent steroidogenesis is induced at all levels of the toxin. Steroidogenic responses are detectable with 10 pg/ml of choleragen or less. The respective effects of ACTH and choleragen on cyclic-AMP synthesis and release into the medium parallel those on steroidogenesis. Intracellular cyclic-AMP levels in ACTH-treated cells reach a peak within 20-30 minutes and decline to normal levels within 2-4 hours. In choleragen-treated cells, after the lage period, the levels of intracellular cyclic-AMP remain above control levels indefinitely. The effects of ACTH and choleragen on cyclic-AMP biosynthesis are additive at all levels of the two compounds. The effects of choleragen are blocked by prior treatment of the toxin with a five-fold molar excess of ganglioside GM1, a presumed constituent of the toxin-binding site."} {"id": "PMID:168057", "title": "Lipolytic action of human chorionic somatomammotropin.", "content": "Human chorionic somatomammotropin extracted and purified from placenta at term was proved to have a lipolytic action in the epididymal fat pad of rats. The following mechanism appears to be involved in the lipolytic action of the hormone; human chorionic somatomammotropin activates adenyl cyclase, thereby increasing the concentration of cyclic AMP in the tissue, which, in turn, activates protein kinase to lead to the activation of hormone sensitive lipase.", "contents": "Lipolytic action of human chorionic somatomammotropin. Human chorionic somatomammotropin extracted and purified from placenta at term was proved to have a lipolytic action in the epididymal fat pad of rats. The following mechanism appears to be involved in the lipolytic action of the hormone; human chorionic somatomammotropin activates adenyl cyclase, thereby increasing the concentration of cyclic AMP in the tissue, which, in turn, activates protein kinase to lead to the activation of hormone sensitive lipase."} {"id": "PMID:168058", "title": "The effects of cyclic AMP, theophylline, angiotensin II and electrolytes upon renin release from rat kidney slices.", "content": "The effects of cyclic AMP, theophylline, angiotensin II and electrolytes upon renin release were examined by incubation of rat kidney slices. Angiotensin inhibited renin release with increasing concentrations. On the other hand, cyclic AMP and theophylline stimulated it. Calcium also seemed to play an important role in the control of renin release from kidney slices. However, the direct effects of sodium and potassium upon renin release were not conspicuous.", "contents": "The effects of cyclic AMP, theophylline, angiotensin II and electrolytes upon renin release from rat kidney slices. The effects of cyclic AMP, theophylline, angiotensin II and electrolytes upon renin release were examined by incubation of rat kidney slices. Angiotensin inhibited renin release with increasing concentrations. On the other hand, cyclic AMP and theophylline stimulated it. Calcium also seemed to play an important role in the control of renin release from kidney slices. However, the direct effects of sodium and potassium upon renin release were not conspicuous."} {"id": "PMID:168059", "title": "A case report of Turner's syndrome with ring X chromosome.", "content": "A case of Turner's syndrome with short stature and 45, XO/46, XXr mosaicism in chromosome study was presented. With special emphasis on endocrinological study, the size of the breasts was normal in contrast to the poor development of the breasts in most of types of Turner's syndrome. She showed normal thyroid function, slightly low level of urinary 17-OHCS, decreased 17-KS, poor response in metopirone test and poor response of HGH to insulin.", "contents": "A case report of Turner's syndrome with ring X chromosome. A case of Turner's syndrome with short stature and 45, XO/46, XXr mosaicism in chromosome study was presented. With special emphasis on endocrinological study, the size of the breasts was normal in contrast to the poor development of the breasts in most of types of Turner's syndrome. She showed normal thyroid function, slightly low level of urinary 17-OHCS, decreased 17-KS, poor response in metopirone test and poor response of HGH to insulin."} {"id": "PMID:168060", "title": "Qualitative abnormality of insulin secretion in a case with insulinoma.", "content": "We have presented here a case of atypical insulinoma. Despite the recurrent episodes of hypoglycemic symptoms, the plasma level of insulin has never been excessive at fasting or by regular provocative tests. Detailed examination had demonstrated qualitative abnormality of insulin secretion. Hyposuppressibility of insulin secretion by hypoglycemia, borderline diabetic curve of glucose tolerance test, blunted response ot insulin to glucagon and leucine were the principle characteristics of these abnormalities. After removal of adenoma, insulin response to glucose, glucagon and leucine was improved. Only secretion provoked a high level of insulin and this abnormal elevation was no longer seen after the removal of adenoma. A removed elevation was no longer seen after the removal of adenoma. A removed insulinoma contained 25 U of immunoreactive insulin per gram tissue, but was negative for aldehyde-fuchsin staining. On electromicroscopy only atypical beta-cell granules were seen.", "contents": "Qualitative abnormality of insulin secretion in a case with insulinoma. We have presented here a case of atypical insulinoma. Despite the recurrent episodes of hypoglycemic symptoms, the plasma level of insulin has never been excessive at fasting or by regular provocative tests. Detailed examination had demonstrated qualitative abnormality of insulin secretion. Hyposuppressibility of insulin secretion by hypoglycemia, borderline diabetic curve of glucose tolerance test, blunted response ot insulin to glucagon and leucine were the principle characteristics of these abnormalities. After removal of adenoma, insulin response to glucose, glucagon and leucine was improved. Only secretion provoked a high level of insulin and this abnormal elevation was no longer seen after the removal of adenoma. A removed elevation was no longer seen after the removal of adenoma. A removed insulinoma contained 25 U of immunoreactive insulin per gram tissue, but was negative for aldehyde-fuchsin staining. On electromicroscopy only atypical beta-cell granules were seen."} {"id": "PMID:168061", "title": "A case of acromegaly improved by pituitary apoplexy.", "content": "This report deals with a detailed course of one patient with acromegaly who had a pituitary apoplexy. The pituitary apoplexy occurred suddenly 5 days after administration of a oral hypoglycemic agent, buformin, during hospitalization. Immediately after the attack changes of the concentrations of several hormones such as serum growth-hormone, serum thyroid hormone and urinary 17-hydroxycorticosteroids were followed until the development to hypopituitary state. Simultaneously with the decrease of the concentrations of the above-mentioned hormones, a regression of the physical manifestations of acromegaly and a complete amelioration of diabetes mellitus were observed.", "contents": "A case of acromegaly improved by pituitary apoplexy. This report deals with a detailed course of one patient with acromegaly who had a pituitary apoplexy. The pituitary apoplexy occurred suddenly 5 days after administration of a oral hypoglycemic agent, buformin, during hospitalization. Immediately after the attack changes of the concentrations of several hormones such as serum growth-hormone, serum thyroid hormone and urinary 17-hydroxycorticosteroids were followed until the development to hypopituitary state. Simultaneously with the decrease of the concentrations of the above-mentioned hormones, a regression of the physical manifestations of acromegaly and a complete amelioration of diabetes mellitus were observed."} {"id": "PMID:168062", "title": "Reserpine induced changes in the estradiol uptake by the pituitary and the uterus in ovariectomized rats.", "content": "Reserpine treatment produced a marked decrease of the in vitro binding of estradiol to the nuclear fraction of the uterus. A similar observation was made when reserpine was given into the incubation medium of uterine tissue. In contrast to these findings both in vitro and in vivo reserpine administration resulted in an increase of the estradiol binding to the nuclear fraction of the anterior pituitary in ovariectomized rats. The binding capacity of cytosol fraction after reserpine administration did not show significant alterations. In addition to these observations it is worth to mention that reserpine treatment resulted in a significant decrease of the estradiol-induced increase of uterus weight in ovariectomized rats.", "contents": "Reserpine induced changes in the estradiol uptake by the pituitary and the uterus in ovariectomized rats. Reserpine treatment produced a marked decrease of the in vitro binding of estradiol to the nuclear fraction of the uterus. A similar observation was made when reserpine was given into the incubation medium of uterine tissue. In contrast to these findings both in vitro and in vivo reserpine administration resulted in an increase of the estradiol binding to the nuclear fraction of the anterior pituitary in ovariectomized rats. The binding capacity of cytosol fraction after reserpine administration did not show significant alterations. In addition to these observations it is worth to mention that reserpine treatment resulted in a significant decrease of the estradiol-induced increase of uterus weight in ovariectomized rats."} {"id": "PMID:168063", "title": "Effects of temperature on interictal discharge at penicillin epileptogenic foci.", "content": "The effects of local brain temperature on acute focal penicillin epilepsy in the exposed hippocampus of cat were studied. Results from anesthetized and from immobilized, unanesthetized animals were compared. Over the temperature range 26 to 43 degrees C (at the alveus), the interictal spike interval and duration of the spike discharge varied inversely with temperature. The former showed a Q10 of 2.4 and the latter a Q10 of 1.5, with no difference due to type of preparation. A significant trans-hippocampal thermal gradient may imply that these values are underestimates by 20% or more. The low Q10 of duration of the paroxysmal discharge was consistent with the known temperature dependence of impulse conduction velocity of intracortical neural networks. The high Q10 of the interictal interval, on the other hand, was consistent with the view that some slow endogenous, perhaps metabolic factor such as a NA,K-ATPase modulated excitability at the focus of penicillin spikes.", "contents": "Effects of temperature on interictal discharge at penicillin epileptogenic foci. The effects of local brain temperature on acute focal penicillin epilepsy in the exposed hippocampus of cat were studied. Results from anesthetized and from immobilized, unanesthetized animals were compared. Over the temperature range 26 to 43 degrees C (at the alveus), the interictal spike interval and duration of the spike discharge varied inversely with temperature. The former showed a Q10 of 2.4 and the latter a Q10 of 1.5, with no difference due to type of preparation. A significant trans-hippocampal thermal gradient may imply that these values are underestimates by 20% or more. The low Q10 of duration of the paroxysmal discharge was consistent with the known temperature dependence of impulse conduction velocity of intracortical neural networks. The high Q10 of the interictal interval, on the other hand, was consistent with the view that some slow endogenous, perhaps metabolic factor such as a NA,K-ATPase modulated excitability at the focus of penicillin spikes."} {"id": "PMID:168064", "title": "Attempts to produce spike-and-wave complexes in the electrocorticogram of the rat.", "content": "The effects of several procedures for inducing spike-and-wave complexes in other experimental animals have been examined in the rat. Systemic convulsants, pentylenetetrazol, methionine sulfoximine and fluoroacetate, topical picrotoxin, and bilateral implants of cobalt produced the appearance of polyspike discharges in the ECoG. Topical application of conjugated estrogens to both frontal cortices elicited single spike-and-slow-wave complexes which did not repeat at 3 to 5 cps. These results suggest that the rat is not a suitable species for a detailed study of spike-and-wave production.", "contents": "Attempts to produce spike-and-wave complexes in the electrocorticogram of the rat. The effects of several procedures for inducing spike-and-wave complexes in other experimental animals have been examined in the rat. Systemic convulsants, pentylenetetrazol, methionine sulfoximine and fluoroacetate, topical picrotoxin, and bilateral implants of cobalt produced the appearance of polyspike discharges in the ECoG. Topical application of conjugated estrogens to both frontal cortices elicited single spike-and-slow-wave complexes which did not repeat at 3 to 5 cps. These results suggest that the rat is not a suitable species for a detailed study of spike-and-wave production."} {"id": "PMID:168066", "title": "Oxidation of succinate in heart, brain, and kidney mitochondria in hypobaria and hypoxia.", "content": "Exposure of rats to hypobaric stress for periods of up to 36 h caused a consistent change in the succinate-NT reductase activity of the heart mitochondria whereas there was no significant change in the activities of either succinate dehydrogenase and succinate-NT reductase of the brain and the kidney. Mitochondrial succinate dehydrogenase of the heart, the brain and the kidney was activated 2- to 7-fold with the substrate and malonate. The activations obtained with oxalate, citrate and dinitrophenol were relatively lower in comparison to succinate and malonate. Benzohydroquinone and 2-nitrophenol had no stimulatory effect on the heart, the brain and the kidney mitochondria. THE ACTIVATIONS OBTAINED WITH THE VARIOUS EFFECTORS PARTIALLY (OR COMPLETELY IN THE CASE OF SUCCINATE) REVERSED ON WASHING THE MITOCHONDRIAL SAMPLES WITH THE SUCROSE HOMOGENIZING MEDIUM. The effect of ubiquinol, which also activated the enzyme, was only partially reversed after the second preincubation with succinate in the brain and the kidney whereas in the heart the activity was fully reversed. The increased activity of succinate dehydrogenase obtained with ATP and ADP was further enhanced by Mg2+ exclusively in the brain mitochondria, suggesting the possibility of Mg2+-AIP complex as the active species. Succinate-NT reductase of the heart, the brain and the kidney mitochondria showed a high activation with ubiquinone whereas its reduced form had no stimulatory effect.", "contents": "Oxidation of succinate in heart, brain, and kidney mitochondria in hypobaria and hypoxia. Exposure of rats to hypobaric stress for periods of up to 36 h caused a consistent change in the succinate-NT reductase activity of the heart mitochondria whereas there was no significant change in the activities of either succinate dehydrogenase and succinate-NT reductase of the brain and the kidney. Mitochondrial succinate dehydrogenase of the heart, the brain and the kidney was activated 2- to 7-fold with the substrate and malonate. The activations obtained with oxalate, citrate and dinitrophenol were relatively lower in comparison to succinate and malonate. Benzohydroquinone and 2-nitrophenol had no stimulatory effect on the heart, the brain and the kidney mitochondria. THE ACTIVATIONS OBTAINED WITH THE VARIOUS EFFECTORS PARTIALLY (OR COMPLETELY IN THE CASE OF SUCCINATE) REVERSED ON WASHING THE MITOCHONDRIAL SAMPLES WITH THE SUCROSE HOMOGENIZING MEDIUM. The effect of ubiquinol, which also activated the enzyme, was only partially reversed after the second preincubation with succinate in the brain and the kidney whereas in the heart the activity was fully reversed. The increased activity of succinate dehydrogenase obtained with ATP and ADP was further enhanced by Mg2+ exclusively in the brain mitochondria, suggesting the possibility of Mg2+-AIP complex as the active species. Succinate-NT reductase of the heart, the brain and the kidney mitochondria showed a high activation with ubiquinone whereas its reduced form had no stimulatory effect."} {"id": "PMID:168067", "title": "Regulatory properties of purified 3-phosphoglycerate dehydrogenase from Bacillus subtilis.", "content": "3-Phosphoglycerate dehydrogenase (3-phosphoglycerate:NAD oxidoreductase, EC. 1.1.1.95) was purified from Bacillus subtilis by conventional methods. The final preparation was homogeneous by electrophoretic analysis and had a sedimentation constant of 6.3 S. On the basis of gel filtration data the enzyme had a molecular weight of about 166000. The plot of velocity versus phosphoglycerate concentration was biphasic while similar plots for hydroxypyruvate phosphate and NADH were the conventional hyperbolic type. The enzyme was specifically inhibited by serine. The inhibition was time dependent, requiring several minutes incubation before a constant level of inhibition was achieved. Serine inhibition was of the \"mixed type\" with respect to 3-phosphoglycerate and Hill plots of these data had slopes that approached 2. Desensitization of the enzyme to serine inhibition was achieved by incubation in the absence of dithiothreitol. The desensitized enzyme was different from the native enzyme in fluoresence properties, sedimentation characteristics and in the absence of the biphasic phosphoglycerate saturation curve. Evidence was obtained for the participation of sulphydryl groups in the changes in protein structure responsible for serine inhibition as well as the dehydrogenase activity of the enzyme.", "contents": "Regulatory properties of purified 3-phosphoglycerate dehydrogenase from Bacillus subtilis. 3-Phosphoglycerate dehydrogenase (3-phosphoglycerate:NAD oxidoreductase, EC. 1.1.1.95) was purified from Bacillus subtilis by conventional methods. The final preparation was homogeneous by electrophoretic analysis and had a sedimentation constant of 6.3 S. On the basis of gel filtration data the enzyme had a molecular weight of about 166000. The plot of velocity versus phosphoglycerate concentration was biphasic while similar plots for hydroxypyruvate phosphate and NADH were the conventional hyperbolic type. The enzyme was specifically inhibited by serine. The inhibition was time dependent, requiring several minutes incubation before a constant level of inhibition was achieved. Serine inhibition was of the \"mixed type\" with respect to 3-phosphoglycerate and Hill plots of these data had slopes that approached 2. Desensitization of the enzyme to serine inhibition was achieved by incubation in the absence of dithiothreitol. The desensitized enzyme was different from the native enzyme in fluoresence properties, sedimentation characteristics and in the absence of the biphasic phosphoglycerate saturation curve. Evidence was obtained for the participation of sulphydryl groups in the changes in protein structure responsible for serine inhibition as well as the dehydrogenase activity of the enzyme."} {"id": "PMID:168068", "title": "Effects of triiodothyronine on rat-liver mitochondrial transcription process.", "content": "1. In order to demonstrate that triiodothyronine affects mitochondrial RNA synthesis by acting on the enzyme component of the DNA. RNA polymerase complex, mitochondrial RNA polymerase from thyroidectomized and hormone-treated rats was purified up to a stage in which activity was dependent on the addition of exogenous template. In these conditions and using different DNAs as templates, the enzyme from hormone-treated animals displayed an activity about double that of the activity of thyroidectomized animals. 2. Measurements of stability of mitochondrial RNA synthesized in vitro suggest, however, that the hormone can act also at the template level in mitochondrial transcription: the RNA population synthesized in vitro from hormone-treated rats is indeed much more enriched in unstable, probably messenger, RNA species. 3. The turnover of mitochondrial messenger RNA is higher after hormone treatment. 4. Adenosine cyclic 3':5'-monophosphate (cAMP) and its dibutyryl derivative added in vitro to mitochondria from thyroidectomized animals do not affect the incorporation of labeled precursor into mitochondrial RNA, suggesting that the level of the cyclic nucleotide in mitochondria is probably not involved in the hormone action. 5. It is concluded from these and previous studies that the thyroid hormone affects more than one parameter in the mitochondrial transcription process. The interrelationship between these events at molecular level remains, however, to be clarified.", "contents": "Effects of triiodothyronine on rat-liver mitochondrial transcription process. 1. In order to demonstrate that triiodothyronine affects mitochondrial RNA synthesis by acting on the enzyme component of the DNA. RNA polymerase complex, mitochondrial RNA polymerase from thyroidectomized and hormone-treated rats was purified up to a stage in which activity was dependent on the addition of exogenous template. In these conditions and using different DNAs as templates, the enzyme from hormone-treated animals displayed an activity about double that of the activity of thyroidectomized animals. 2. Measurements of stability of mitochondrial RNA synthesized in vitro suggest, however, that the hormone can act also at the template level in mitochondrial transcription: the RNA population synthesized in vitro from hormone-treated rats is indeed much more enriched in unstable, probably messenger, RNA species. 3. The turnover of mitochondrial messenger RNA is higher after hormone treatment. 4. Adenosine cyclic 3':5'-monophosphate (cAMP) and its dibutyryl derivative added in vitro to mitochondria from thyroidectomized animals do not affect the incorporation of labeled precursor into mitochondrial RNA, suggesting that the level of the cyclic nucleotide in mitochondria is probably not involved in the hormone action. 5. It is concluded from these and previous studies that the thyroid hormone affects more than one parameter in the mitochondrial transcription process. The interrelationship between these events at molecular level remains, however, to be clarified."} {"id": "PMID:168069", "title": "Existence of two alternative pathways for fructose and sorbitol metabolism in Bacillus subtilis Marburg.", "content": "Strains of Bacillus subtilis mutated for fructose phosphotransferase system (fruA), fructose-1-phosphate kinase (fruB), fructokinase (frucC) have been tested for their catabolism of sorbitol and fructose. It is shown that the previously known pathways of sorbitol and fructose degradation in B. subtilis, e.g.: (see article) may metabolize intracellular fructose produced either by sorbitol oxidation or by fructose-1-phosphate dephosphorylation. The intracellular fructore degradation via fructose-1-phosphate kinase has been found to require the fructose phosphotransferase system which ensures a vectorial transport of fructose.", "contents": "Existence of two alternative pathways for fructose and sorbitol metabolism in Bacillus subtilis Marburg. Strains of Bacillus subtilis mutated for fructose phosphotransferase system (fruA), fructose-1-phosphate kinase (fruB), fructokinase (frucC) have been tested for their catabolism of sorbitol and fructose. It is shown that the previously known pathways of sorbitol and fructose degradation in B. subtilis, e.g.: (see article) may metabolize intracellular fructose produced either by sorbitol oxidation or by fructose-1-phosphate dephosphorylation. The intracellular fructore degradation via fructose-1-phosphate kinase has been found to require the fructose phosphotransferase system which ensures a vectorial transport of fructose."} {"id": "PMID:168070", "title": "The mechanism of action of methionyl-tRNA synthetase from Escherichia coli. Inhibition by adenosine and 8-aminoadenosine of the amino-acid activation reaction.", "content": "Adenosine and 8-aminoadenosine, both competitive inhibitors of ATP-Mg2+ in the ATP-PPi exchange reaction catalyzed by methionyl-tRNA synthetase, are used to investigate the active center for methionyl-adenylate formation. Resolution of the kinetics parameters of the reaction indicates that methionine markedly enhances the affinity of the nucleosides for the enzyme, providing evidence for coupling between the sites for amino acid and the nucleoside moiety of ATP. Furthermore, occupation of both of these sites is a prerequisite for binding of pyrophosphate. Introduction of an amino group in position 8 of the adenine ring strongly increases the affinity constants for the nucleoside and for pyrophosphate in the coupled reactions described above.", "contents": "The mechanism of action of methionyl-tRNA synthetase from Escherichia coli. Inhibition by adenosine and 8-aminoadenosine of the amino-acid activation reaction. Adenosine and 8-aminoadenosine, both competitive inhibitors of ATP-Mg2+ in the ATP-PPi exchange reaction catalyzed by methionyl-tRNA synthetase, are used to investigate the active center for methionyl-adenylate formation. Resolution of the kinetics parameters of the reaction indicates that methionine markedly enhances the affinity of the nucleosides for the enzyme, providing evidence for coupling between the sites for amino acid and the nucleoside moiety of ATP. Furthermore, occupation of both of these sites is a prerequisite for binding of pyrophosphate. Introduction of an amino group in position 8 of the adenine ring strongly increases the affinity constants for the nucleoside and for pyrophosphate in the coupled reactions described above."} {"id": "PMID:168072", "title": "Chlorothricin, and inhibitor of porcine-heart malate dehydrogenases, discriminating between the mitochondrial and cytoplasmic isoenzyme.", "content": "The macrolide-type antibiotic chlorothricin was found to inhibit both the mitochondrial and the cytoplasmic form of pig heart malate dehydrogenase. Steady-state kinetic measurements revealed that in the direction of oxalacetate reduction chlorothricin is competitive with respect to NADH and non-competitive with respect to oxalacetate. Both the variation of initial velocity with NADH concentration in the presence of antibiotic, and, at several fixed levels of NADH, the variation of initial velocity with chlorothricin concentration deviates from the classical Michaelis-Menten relationship for the two isoenzymes. Since, despite the very similar kinetic behaviour of the mitochondrial and cytoplasmic species of malate dehydrogenase, the concentration of chlorothricin required for half-maximal inhibition of the two enzymes differs by more than a factor of 10 (the mitochondrial isoenzyme being more susceptible to inhibition), it is concluded that the NADH binding sites of the mitochondrial and cytoplasmic form of malate dehydrogenase from pig heart are different.", "contents": "Chlorothricin, and inhibitor of porcine-heart malate dehydrogenases, discriminating between the mitochondrial and cytoplasmic isoenzyme. The macrolide-type antibiotic chlorothricin was found to inhibit both the mitochondrial and the cytoplasmic form of pig heart malate dehydrogenase. Steady-state kinetic measurements revealed that in the direction of oxalacetate reduction chlorothricin is competitive with respect to NADH and non-competitive with respect to oxalacetate. Both the variation of initial velocity with NADH concentration in the presence of antibiotic, and, at several fixed levels of NADH, the variation of initial velocity with chlorothricin concentration deviates from the classical Michaelis-Menten relationship for the two isoenzymes. Since, despite the very similar kinetic behaviour of the mitochondrial and cytoplasmic species of malate dehydrogenase, the concentration of chlorothricin required for half-maximal inhibition of the two enzymes differs by more than a factor of 10 (the mitochondrial isoenzyme being more susceptible to inhibition), it is concluded that the NADH binding sites of the mitochondrial and cytoplasmic form of malate dehydrogenase from pig heart are different."} {"id": "PMID:168073", "title": "Deterioration of rat-liver mitochondria during isopycnic centrifugation in an isoosmotic medium.", "content": "We have investigated the effect of the centrifugation speed on the behavior of rat-liver mitochondria during isopycnic centrifugation in an isoosmotic medium. The gradient was made with a macromolecular compound, glycogen dissolved in 0.25 M aqueous sucrose. The distribution curves of several mitochondrial enzymes change when the centrifugation reaches a certain speed: they are shifted toward regions of lower density. The results are plausibly explained by supposing that the inner mitochondrial membrane becomes permeable to sucrose at high centrifugation speeds, and that the granules swell. The main causal agent of the phenomenon is the hydrostatic pressure the mitochondria are subjected to during centrifugation. Morphological observations show that mitochondria are markedly deteriorated when centrifuged at high speed in the glycogen gradient; they are swollen and the outer membrane is broken; also frequently, a large electron-dense granule is seen in the matrix near the inner mambrane.", "contents": "Deterioration of rat-liver mitochondria during isopycnic centrifugation in an isoosmotic medium. We have investigated the effect of the centrifugation speed on the behavior of rat-liver mitochondria during isopycnic centrifugation in an isoosmotic medium. The gradient was made with a macromolecular compound, glycogen dissolved in 0.25 M aqueous sucrose. The distribution curves of several mitochondrial enzymes change when the centrifugation reaches a certain speed: they are shifted toward regions of lower density. The results are plausibly explained by supposing that the inner mitochondrial membrane becomes permeable to sucrose at high centrifugation speeds, and that the granules swell. The main causal agent of the phenomenon is the hydrostatic pressure the mitochondria are subjected to during centrifugation. Morphological observations show that mitochondria are markedly deteriorated when centrifuged at high speed in the glycogen gradient; they are swollen and the outer membrane is broken; also frequently, a large electron-dense granule is seen in the matrix near the inner mambrane."} {"id": "PMID:168074", "title": "Blocks in elongation and initiation of protein synthesis induced by interferon treatment in mouse L cells.", "content": "Synthesis of polypeptide chains coded by exogenous messenger RNAs is inhibited in cell-free extracts from interferon-treated mouse L cells, due to a \"deficiency\" in some specific tRNA species. A detailed analysis shows that polypeptide chain elongation is blocked and incomplete chains are formed. After a few minutes, however, initiation of new polypeptide chains is also blocked. Messenger RNA still binds to ribosomes but initiator Met-tRNA(FMET) binding is inhibited. The block in initiation appears to be secondary to the block in elongation.", "contents": "Blocks in elongation and initiation of protein synthesis induced by interferon treatment in mouse L cells. Synthesis of polypeptide chains coded by exogenous messenger RNAs is inhibited in cell-free extracts from interferon-treated mouse L cells, due to a \"deficiency\" in some specific tRNA species. A detailed analysis shows that polypeptide chain elongation is blocked and incomplete chains are formed. After a few minutes, however, initiation of new polypeptide chains is also blocked. Messenger RNA still binds to ribosomes but initiator Met-tRNA(FMET) binding is inhibited. The block in initiation appears to be secondary to the block in elongation."} {"id": "PMID:168075", "title": "Gylcerol-3-phosphate shuttle and its function in intermediary metabolism of hamster brown-adipose tissue.", "content": "1. Brown adipose tissue of the hamster possesses high specific activities of soluble, cytoplasmic NAD-linked, as well as mitochondrial flavin-coupled, glycerol-3-phosphate dehydrogenases. The ratio of the two enzyme activities is high (close to 1), when compared with other tissues of the hamster. 2. In the presence of rotenone, NADH is oxidised very poorly by homogenates of brown adipose tissue. A high rate of oxidation is obtained upon further addition of dihydroxyacetone phosphate, which itself is negligible oxidised. When followed fluorimetrically glycerol 3-phosphate can also be observed to induce NADH oxidation, but only after a significant lag time. Similar results are obtained with isolated mitochondria plus high-speed supernatant. With high-speed supernatant alone, only dihydroxyacetone phosphate has any effect, whereas with isolated mitochondria neither dihydroxyacetone phosphate nor glycerol 3-phosphate induce any NADH disappearance. 3. Respiration induced by NADH plus dihydroxyacetone phosphate in homogenates equals 56% of the respiration induced by glycerol 3-phosphate alone. 4. Respiration induced by NADH plus dihydroxyacetone phosphate, as well as that induced by glycerol 3-phosphate, is inhibited by the same concentrations of inhibitors as are required for inhibition of the mitochondrial dehydrogenase i.e. EDTA, long-chain unsaturated fatty acids, long-chain fatty acyl CoA esters. 5. In isolated brown adipocytes in the presence of rotenone, norepinephrine significantly inhibits respiration induced by glycerol 3-phosphate. 6. The results obtained are discussed with respect to the role of glycerol 3-phosphate as an electron sink for cytosolic reducing equivalents to maintain a low level of extramitochondrial NADH. A means of maintaining a level of glycerol 3-phosphate adequate for triglyceride synthesis is also considered.", "contents": "Gylcerol-3-phosphate shuttle and its function in intermediary metabolism of hamster brown-adipose tissue. 1. Brown adipose tissue of the hamster possesses high specific activities of soluble, cytoplasmic NAD-linked, as well as mitochondrial flavin-coupled, glycerol-3-phosphate dehydrogenases. The ratio of the two enzyme activities is high (close to 1), when compared with other tissues of the hamster. 2. In the presence of rotenone, NADH is oxidised very poorly by homogenates of brown adipose tissue. A high rate of oxidation is obtained upon further addition of dihydroxyacetone phosphate, which itself is negligible oxidised. When followed fluorimetrically glycerol 3-phosphate can also be observed to induce NADH oxidation, but only after a significant lag time. Similar results are obtained with isolated mitochondria plus high-speed supernatant. With high-speed supernatant alone, only dihydroxyacetone phosphate has any effect, whereas with isolated mitochondria neither dihydroxyacetone phosphate nor glycerol 3-phosphate induce any NADH disappearance. 3. Respiration induced by NADH plus dihydroxyacetone phosphate in homogenates equals 56% of the respiration induced by glycerol 3-phosphate alone. 4. Respiration induced by NADH plus dihydroxyacetone phosphate, as well as that induced by glycerol 3-phosphate, is inhibited by the same concentrations of inhibitors as are required for inhibition of the mitochondrial dehydrogenase i.e. EDTA, long-chain unsaturated fatty acids, long-chain fatty acyl CoA esters. 5. In isolated brown adipocytes in the presence of rotenone, norepinephrine significantly inhibits respiration induced by glycerol 3-phosphate. 6. The results obtained are discussed with respect to the role of glycerol 3-phosphate as an electron sink for cytosolic reducing equivalents to maintain a low level of extramitochondrial NADH. A means of maintaining a level of glycerol 3-phosphate adequate for triglyceride synthesis is also considered."} {"id": "PMID:168076", "title": "Iron-sulfur components of succinate dehydrogenase: stoichiometry and kinetic behavior in activated preparations.", "content": "Extensively or completely activated preparations of beef heart succinate dehydrogenase have been investigated by electron paramagnetic resonance (EPR) techniques at 6 to 97 K. Reductive titrations with dithionite and rapid kinetic studies were performed with various types of soluble and membrane-bound preparations of the enzyme. The following components were detected and their behavior analyzed: a free radical, presumably arising from the covalently bound flavin on reduction, two iron-sulfur centers of the ferredoxin type, the signals of which appear on reduction, and a highpotential iron-sulfur component, detectable in the oxidized state. The high-potential component was only detected in complex II and inner-membrane preparations. This component and one of the ferredoxin-type centers were present in amounts close to stoichiometric with the flavin and were reduced by substrate. The other ferredoxin-type center was present in amounts between 0.1 and 0.5 times that of the flavin and was reduced only by dithionite. Of the components reduced by succinate, however, only a fraction (up to 50% of the high-potential iron-sulfur center and 40-60% of the ferredoxin-type iron-sulfur center) was reduced within the turnover time of the enzymes; In complex II not more than about 10% of the flavin appeared in the semiquinone form at any time. Soluble, purified preparations behaved similarly except that the high-potential component was nearly or completely absent and extensive accumulation of the free radical occurred (up to 70 to 80% of the flavin) in titration and kinetic experiments. No significant difference was observed between the rates of semiquinone formation and the reduction of the ferredoxin-type or high-potential centers by the substrate. Also no qualitative differences in the properties studied in this work became apparent between prepatations containing 4 or 8 iron atoms, respectively.", "contents": "Iron-sulfur components of succinate dehydrogenase: stoichiometry and kinetic behavior in activated preparations. Extensively or completely activated preparations of beef heart succinate dehydrogenase have been investigated by electron paramagnetic resonance (EPR) techniques at 6 to 97 K. Reductive titrations with dithionite and rapid kinetic studies were performed with various types of soluble and membrane-bound preparations of the enzyme. The following components were detected and their behavior analyzed: a free radical, presumably arising from the covalently bound flavin on reduction, two iron-sulfur centers of the ferredoxin type, the signals of which appear on reduction, and a highpotential iron-sulfur component, detectable in the oxidized state. The high-potential component was only detected in complex II and inner-membrane preparations. This component and one of the ferredoxin-type centers were present in amounts close to stoichiometric with the flavin and were reduced by substrate. The other ferredoxin-type center was present in amounts between 0.1 and 0.5 times that of the flavin and was reduced only by dithionite. Of the components reduced by succinate, however, only a fraction (up to 50% of the high-potential iron-sulfur center and 40-60% of the ferredoxin-type iron-sulfur center) was reduced within the turnover time of the enzymes; In complex II not more than about 10% of the flavin appeared in the semiquinone form at any time. Soluble, purified preparations behaved similarly except that the high-potential component was nearly or completely absent and extensive accumulation of the free radical occurred (up to 70 to 80% of the flavin) in titration and kinetic experiments. No significant difference was observed between the rates of semiquinone formation and the reduction of the ferredoxin-type or high-potential centers by the substrate. Also no qualitative differences in the properties studied in this work became apparent between prepatations containing 4 or 8 iron atoms, respectively."} {"id": "PMID:168078", "title": "Lysophospholipids in pig pancreatic zymogen granules in relation to exocytosis.", "content": "A hypothesis to explain the stimulatory role of cyclic AMP (adenosine 3':5'-monophosphate) in pancreatic enzyme secretion. has been tested. In this hypothesis cyclic AMP would activate a phospholipase activity, which would lead to a locally increased lysophospholipid formation, resulting in a fusion between the zymogen granule membrane and the apical plasma membrane. Cyclic AMP added to isolated pig pancreatic zymogen granules leads to an increased lysis of these granules, but the slowness of this effect makes its physiological significance dubious. In pancreatic homogenates or zymogen granules no stimulating effect of cyclic AMP on lipase of phospholipase activity could be demonstrated. Isolated zymogen granules have a high lysophospholipid content (27% of total phospholipids), consisting of the 1-acyl and 2-acyl forms of lysophosphatidylcholine and lysophosphatidylethanolamine. Experiments with radioactive phosphatidylcholine indicate that the lysophospholipids are due to the action of endogenous (phospho)lipases during the isolation procedure. It is concluded that these experiments do not lend support to the above hypothesis for the mechanism of action of cyclic AMP in pancreatic enzyme secretion", "contents": "Lysophospholipids in pig pancreatic zymogen granules in relation to exocytosis. A hypothesis to explain the stimulatory role of cyclic AMP (adenosine 3':5'-monophosphate) in pancreatic enzyme secretion. has been tested. In this hypothesis cyclic AMP would activate a phospholipase activity, which would lead to a locally increased lysophospholipid formation, resulting in a fusion between the zymogen granule membrane and the apical plasma membrane. Cyclic AMP added to isolated pig pancreatic zymogen granules leads to an increased lysis of these granules, but the slowness of this effect makes its physiological significance dubious. In pancreatic homogenates or zymogen granules no stimulating effect of cyclic AMP on lipase of phospholipase activity could be demonstrated. Isolated zymogen granules have a high lysophospholipid content (27% of total phospholipids), consisting of the 1-acyl and 2-acyl forms of lysophosphatidylcholine and lysophosphatidylethanolamine. Experiments with radioactive phosphatidylcholine indicate that the lysophospholipids are due to the action of endogenous (phospho)lipases during the isolation procedure. It is concluded that these experiments do not lend support to the above hypothesis for the mechanism of action of cyclic AMP in pancreatic enzyme secretion"} {"id": "PMID:168079", "title": "Interactions of heteroaromatic compounds with nucleic acids. 2. Influence of substituents on the base and sequence specificity of intercalating ligands.", "content": "This paper presents the results of a systematic study on the effects of substituents on the base and sequence specificity of tricyclic heteroaromatic compounds interacting with DNA by intercalation. All the compounds tested are derived from proflavine and acridine orange analogs with different heteroatoms in the middle ring. Their base and sequence specificities were determined by differential dialysis of the ligand against DNA samples of differing G-C content. The main results indicate that (a) the introduction of a phenyl substituent into one of the two available positions of the middle ring increases or decreases the G-C specificity of the ligand depending on the position where the substitution takes place; (b) compounds of the substitution type of neutral red (2-methyl-3-amino-7-dimethyl-amino-phenazine) show unexpectedly high G-C specificities and (c) DNA ligands of pronounced sequence specificity for adjacent G-C pairs can be constructed by combining the structural elements of neutral red with an additional phenyl residue in the same molecule. The further study of compounds related to the phenylated neutral red revealed that the G-C specificity can be improved or destroyed by additional substituents. The comparison of the G-C specificity and the DNA-affinity data of the compounds studied leads to the suggestion that the specificity arises mainly from electronic factors which are strongly controlled through steric constraints on possible ocmplex geometries. As a basis for the discussion a possible structure for the DNA complex of the phenylated neutral red is considered in which the extra phenyl ring at N-5 of the phenazinium system, protrudes into the large groove of the DNA helix while the tricyclic part of the ligand is inserted between the DNA base-pairs.", "contents": "Interactions of heteroaromatic compounds with nucleic acids. 2. Influence of substituents on the base and sequence specificity of intercalating ligands. This paper presents the results of a systematic study on the effects of substituents on the base and sequence specificity of tricyclic heteroaromatic compounds interacting with DNA by intercalation. All the compounds tested are derived from proflavine and acridine orange analogs with different heteroatoms in the middle ring. Their base and sequence specificities were determined by differential dialysis of the ligand against DNA samples of differing G-C content. The main results indicate that (a) the introduction of a phenyl substituent into one of the two available positions of the middle ring increases or decreases the G-C specificity of the ligand depending on the position where the substitution takes place; (b) compounds of the substitution type of neutral red (2-methyl-3-amino-7-dimethyl-amino-phenazine) show unexpectedly high G-C specificities and (c) DNA ligands of pronounced sequence specificity for adjacent G-C pairs can be constructed by combining the structural elements of neutral red with an additional phenyl residue in the same molecule. The further study of compounds related to the phenylated neutral red revealed that the G-C specificity can be improved or destroyed by additional substituents. The comparison of the G-C specificity and the DNA-affinity data of the compounds studied leads to the suggestion that the specificity arises mainly from electronic factors which are strongly controlled through steric constraints on possible ocmplex geometries. As a basis for the discussion a possible structure for the DNA complex of the phenylated neutral red is considered in which the extra phenyl ring at N-5 of the phenazinium system, protrudes into the large groove of the DNA helix while the tricyclic part of the ligand is inserted between the DNA base-pairs."} {"id": "PMID:168080", "title": "The isolation of nuclei and basic nucleoproteins from the cellular slime mold Dictyostelium discoideum.", "content": "A method is described for the isolation of nuclei from an axenic strain of Dictyostelium discoideum using a sorbitol/Ficoll solution and low concentration of Triton X-100. Basic proteins have been extracted from the nuclei and on polyacrylamide gel electrophoresis yield a consistent pattern in which five major groups or bands predominate. Four of these five fractions comigrate with calf thymus histones and one fraction seems to be unique to D. discoideum. The slowest moving of the five fractions is soluble in 0.5 M perchloric acid and comigrates with calf thymus histone F1. After recovery from the perchloric acid solution by precipitation with acetone this fraction yielded one major band on electrophoresis.", "contents": "The isolation of nuclei and basic nucleoproteins from the cellular slime mold Dictyostelium discoideum. A method is described for the isolation of nuclei from an axenic strain of Dictyostelium discoideum using a sorbitol/Ficoll solution and low concentration of Triton X-100. Basic proteins have been extracted from the nuclei and on polyacrylamide gel electrophoresis yield a consistent pattern in which five major groups or bands predominate. Four of these five fractions comigrate with calf thymus histones and one fraction seems to be unique to D. discoideum. The slowest moving of the five fractions is soluble in 0.5 M perchloric acid and comigrates with calf thymus histone F1. After recovery from the perchloric acid solution by precipitation with acetone this fraction yielded one major band on electrophoresis."} {"id": "PMID:168081", "title": "Kinetic equivalence of the active sites of alcohol dehydrogenase from horse liver.", "content": "The reduction, catalysed by liver alcohol dehydrogenase, of benzaldehyde in the presence and absence of pyrazole, and the oxidation of benzyl alcohol and cyclohexanol in the presence of isobutyramide, has been measured by the stopped-flow technique. In performing these experiments particular care was taken to purify the enzyme, coenzymes, substrates and inhibitors, and to minimise as much as possible the effects of a blank substrate reaction. The calculation of the amount of substrate converted to product during the various phases of the transient process was based on the absorption coefficients for the enzyme-coenzyme and enzyme-coenzyme-inhibitor complexes determined in the absence of substrate. The results show that the two active sites of liver alcohol dehydrogenase are kinetically equivalent and that the enzyme does not exhibit half-of-the-sites reactivity.", "contents": "Kinetic equivalence of the active sites of alcohol dehydrogenase from horse liver. The reduction, catalysed by liver alcohol dehydrogenase, of benzaldehyde in the presence and absence of pyrazole, and the oxidation of benzyl alcohol and cyclohexanol in the presence of isobutyramide, has been measured by the stopped-flow technique. In performing these experiments particular care was taken to purify the enzyme, coenzymes, substrates and inhibitors, and to minimise as much as possible the effects of a blank substrate reaction. The calculation of the amount of substrate converted to product during the various phases of the transient process was based on the absorption coefficients for the enzyme-coenzyme and enzyme-coenzyme-inhibitor complexes determined in the absence of substrate. The results show that the two active sites of liver alcohol dehydrogenase are kinetically equivalent and that the enzyme does not exhibit half-of-the-sites reactivity."} {"id": "PMID:168082", "title": "Ribosomal subunit localization of hemoglobin messenger RNA.", "content": "When rabbit reticulocyte polyribosomes are treated with 0.5 M KCl, they dissociate into subunits and release a protein fraction which is required for peptide chain initiation in a cell-free system using KCl-treated subunits as the source of ribosomes. Three independent methods were used to determine the fate of mRNA after KCl treatment of the subunits. These three methods (sucrose gradient analysis of RNA after dissociating it from protein with sodium dodecylsulfate, acrylamide gel electrophoresis of RNA and electron microscopic analysis of subunits) all showed the 8--9-S mRNA to be associated with the small subunit, but not the large subunit. Furthermore, no mRNA was found to be associated with either \"native\" ribosomal subunit in a reticulocyte lysate.", "contents": "Ribosomal subunit localization of hemoglobin messenger RNA. When rabbit reticulocyte polyribosomes are treated with 0.5 M KCl, they dissociate into subunits and release a protein fraction which is required for peptide chain initiation in a cell-free system using KCl-treated subunits as the source of ribosomes. Three independent methods were used to determine the fate of mRNA after KCl treatment of the subunits. These three methods (sucrose gradient analysis of RNA after dissociating it from protein with sodium dodecylsulfate, acrylamide gel electrophoresis of RNA and electron microscopic analysis of subunits) all showed the 8--9-S mRNA to be associated with the small subunit, but not the large subunit. Furthermore, no mRNA was found to be associated with either \"native\" ribosomal subunit in a reticulocyte lysate."} {"id": "PMID:168083", "title": "The sources of plasma cyclic AMP: studies in the rat using isoprenaline, nicotinic acid and glucagon.", "content": "The effects of intravenous administration of isoprenaline, glucagon and nicotinic acid on plasma concentrations of cyclic AMP in rats are described. In order to determine the relative importance of the liver as a source of extracellular cyclic AMP, the effects of the hormones were investigated in intact and functionally hepatectomised rats. The results showed that hepatectomy did not prevent an isoprenaline-stimulated increase in plasma cyclic AMP concentrations, although glucagon was without effect on plasma nucleotide concentrations in this group of animals. It is suggested that the liver is essential for the action of glucagon but that isoprenaline can increase plasma cyclic AMP concentrations in hepatectomised animals by increasing extrahepatic release of the nucleotide. Since inhibition of adipose tissue lipolysis with nicotinic acid did not prevent an isoprenaline or glucagon-stimulated increase in plasma cyclic AMP concentrations, adipose tissue is discounted as a major source of plasma cyclic AMP.", "contents": "The sources of plasma cyclic AMP: studies in the rat using isoprenaline, nicotinic acid and glucagon. The effects of intravenous administration of isoprenaline, glucagon and nicotinic acid on plasma concentrations of cyclic AMP in rats are described. In order to determine the relative importance of the liver as a source of extracellular cyclic AMP, the effects of the hormones were investigated in intact and functionally hepatectomised rats. The results showed that hepatectomy did not prevent an isoprenaline-stimulated increase in plasma cyclic AMP concentrations, although glucagon was without effect on plasma nucleotide concentrations in this group of animals. It is suggested that the liver is essential for the action of glucagon but that isoprenaline can increase plasma cyclic AMP concentrations in hepatectomised animals by increasing extrahepatic release of the nucleotide. Since inhibition of adipose tissue lipolysis with nicotinic acid did not prevent an isoprenaline or glucagon-stimulated increase in plasma cyclic AMP concentrations, adipose tissue is discounted as a major source of plasma cyclic AMP."} {"id": "PMID:168084", "title": "The effect of pregnancy on the control of lipolysis in fat cells isolated from human adipose tissue.", "content": "1. Lipolysis has been estimated by measuring the release of glycerol in isolated adipose tissue cells obtained from women in early prognancy, late pregnancy and 1 - 3 days post partum and from non-pregnant women. 2. Adipocytes of women at the end of pregnancy exhibited higher rates of lipolysis in response to adrenaline (1.5 - 15 muM) plus phentolamine (13 muM) than those of non-pregnant women or those in early pregnancy. 3. Lipolysis in response to adrenaline plus phentolamine in fat cells from women 1 - 3 days post partum was reduced compared to that at the end of gestation but was enhanced relative to that in the non-pregnant or early pregnant state. 4. Basal lipolysis also tended to be greatest at term. 5. Under conditions where the production of cyclic AMP was not rate limiting for the stimulation of lipolysis, that is in the presence of dibutyryl cyclic AMP (1 mM) or adrenaline (15 muM) plus phentolamine (13 muM) plus caffeine (1 mM), the release of glycerol in cells from women at term and in the puerperium was greater than that in women in the non-pregnant or early pregnant state. 6. Cell levels of cyclic AMP rose after incubation with adrenaline (6 muM) plus phentolamine or adrenaline (15 muM) plus phentolamine plus caffeine (1 mM) but were similar in all four groups of women. 7. It is concluded that the observed enhancement of lipolysis demonstrated in fat cells from women at the end of pregnancy reflects an increase in hormone-sensitive lipase activity rather than a modification of hormone receptor site sensitivity or of the rates of synthesis or breakdown of cyclic AMP. 8. This increase in adipose tissue lipolysis at the end of gestation could contribute to the reported rise in plasma nonesterified fatty acids in the final weeks of pregnancy.", "contents": "The effect of pregnancy on the control of lipolysis in fat cells isolated from human adipose tissue. 1. Lipolysis has been estimated by measuring the release of glycerol in isolated adipose tissue cells obtained from women in early prognancy, late pregnancy and 1 - 3 days post partum and from non-pregnant women. 2. Adipocytes of women at the end of pregnancy exhibited higher rates of lipolysis in response to adrenaline (1.5 - 15 muM) plus phentolamine (13 muM) than those of non-pregnant women or those in early pregnancy. 3. Lipolysis in response to adrenaline plus phentolamine in fat cells from women 1 - 3 days post partum was reduced compared to that at the end of gestation but was enhanced relative to that in the non-pregnant or early pregnant state. 4. Basal lipolysis also tended to be greatest at term. 5. Under conditions where the production of cyclic AMP was not rate limiting for the stimulation of lipolysis, that is in the presence of dibutyryl cyclic AMP (1 mM) or adrenaline (15 muM) plus phentolamine (13 muM) plus caffeine (1 mM), the release of glycerol in cells from women at term and in the puerperium was greater than that in women in the non-pregnant or early pregnant state. 6. Cell levels of cyclic AMP rose after incubation with adrenaline (6 muM) plus phentolamine or adrenaline (15 muM) plus phentolamine plus caffeine (1 mM) but were similar in all four groups of women. 7. It is concluded that the observed enhancement of lipolysis demonstrated in fat cells from women at the end of pregnancy reflects an increase in hormone-sensitive lipase activity rather than a modification of hormone receptor site sensitivity or of the rates of synthesis or breakdown of cyclic AMP. 8. This increase in adipose tissue lipolysis at the end of gestation could contribute to the reported rise in plasma nonesterified fatty acids in the final weeks of pregnancy."} {"id": "PMID:168085", "title": "Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity.", "content": "Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the following of its analogues: a) with extended peptide chains at the N-terminal (including \"hormonogens\") Nalpha-glycyl-glycyl-lysine-vasopressin, Nalpha-glycyl-glycyl-glycyl-arginine-vasopressin and Nalpha-D-valyl-lysine-vasopressin, b) \"carba\" modifications desamino-carba6-arginine-vasopressin, desamino-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarba-arginine-vasopressin and c) other steric alterations - desamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C-terminal tripeptide of the molecule- D-arginine or N-methylarginine in sequence position 8 - practically completely eliminated vascular activity. The same was true for Nalpha-D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of a lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-S-, -CH2CH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the \"receptor compartment\". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and uterus and for induction of menstruation.", "contents": "Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity. Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the following of its analogues: a) with extended peptide chains at the N-terminal (including \"hormonogens\") Nalpha-glycyl-glycyl-lysine-vasopressin, Nalpha-glycyl-glycyl-glycyl-arginine-vasopressin and Nalpha-D-valyl-lysine-vasopressin, b) \"carba\" modifications desamino-carba6-arginine-vasopressin, desamino-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarba-arginine-vasopressin and c) other steric alterations - desamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C-terminal tripeptide of the molecule- D-arginine or N-methylarginine in sequence position 8 - practically completely eliminated vascular activity. The same was true for Nalpha-D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of a lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-S-, -CH2CH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the \"receptor compartment\". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and uterus and for induction of menstruation."} {"id": "PMID:168086", "title": "Quantitative iodination of human blood polymorphonuclear leukocytes.", "content": "It was shown by Pincus and Klebanoff that a correlation existed between leukocytic iodination measured in vivo and microbicidal leukocytic activity. We have analyzed the results of this test in relation to time and in the presence of variable quantities of polymorphonuclear leukocytes (PMN). The values observed per time and PMN unit proved to be equivalent in the presence of 2.5 X 105 PMN or 5.0 x 105 PMN per 0.5 ml of incubation medium, measured after 10, 20 and 30 minutes or in the presence of 1.0 x 106 PMN, measured after 10 minutes. That is to say iodination is proportional to leukocyte concentration and incubation time. Increase of either the quantity of cells or the incubation time, beyond the area we defined, reduced iodination per cell and per unit of time. Concerning the patients with an insufficient iodination, we have studied 2 parameters in the presence of 5.0 x 105 PMN: 1) initial iodination measured after 10 and 20 minutes and 2) stability of iodination measured after 60 minutes. These two parameters were equally affected in two cases with myelofi-rosis, 3 patients with acquired refractory anaemia, one with chronic lymphoid leukaemia, one with erythroleukaemia, one with hairy cell leukaemia, one with systemic mastocytosis and almost complete myeloperoxidase dificiency, one with sickle cell disease, two with liver diseases and two with chronic myeloid leukaemia. The iodination at the 60th minute was more affected than at the 10th minute with a patient with myelofibrosis and 4 other patients with acquired refractory anaemias. The significance of these differences is not well understood; however the meaning of the decrease in the iodination of whatever type is that a PMN anomaly exists directly related to the myeloperoxidase H2O2 halogenation system, or to one of the stages of engulfment and/or metabolic events preceeding it and leading to the production of H2O2. This test, with the alterations we introduced, is suggested as a test for detection of functional PMN abnormalities.", "contents": "Quantitative iodination of human blood polymorphonuclear leukocytes. It was shown by Pincus and Klebanoff that a correlation existed between leukocytic iodination measured in vivo and microbicidal leukocytic activity. We have analyzed the results of this test in relation to time and in the presence of variable quantities of polymorphonuclear leukocytes (PMN). The values observed per time and PMN unit proved to be equivalent in the presence of 2.5 X 105 PMN or 5.0 x 105 PMN per 0.5 ml of incubation medium, measured after 10, 20 and 30 minutes or in the presence of 1.0 x 106 PMN, measured after 10 minutes. That is to say iodination is proportional to leukocyte concentration and incubation time. Increase of either the quantity of cells or the incubation time, beyond the area we defined, reduced iodination per cell and per unit of time. Concerning the patients with an insufficient iodination, we have studied 2 parameters in the presence of 5.0 x 105 PMN: 1) initial iodination measured after 10 and 20 minutes and 2) stability of iodination measured after 60 minutes. These two parameters were equally affected in two cases with myelofi-rosis, 3 patients with acquired refractory anaemia, one with chronic lymphoid leukaemia, one with erythroleukaemia, one with hairy cell leukaemia, one with systemic mastocytosis and almost complete myeloperoxidase dificiency, one with sickle cell disease, two with liver diseases and two with chronic myeloid leukaemia. The iodination at the 60th minute was more affected than at the 10th minute with a patient with myelofibrosis and 4 other patients with acquired refractory anaemias. The significance of these differences is not well understood; however the meaning of the decrease in the iodination of whatever type is that a PMN anomaly exists directly related to the myeloperoxidase H2O2 halogenation system, or to one of the stages of engulfment and/or metabolic events preceeding it and leading to the production of H2O2. This test, with the alterations we introduced, is suggested as a test for detection of functional PMN abnormalities."} {"id": "PMID:168087", "title": "Binding of phenoxybenzamine to rat platelets and platelet fractions.", "content": "Irreversible binding of labelled phenoxybenzamine to platelets suspended in Tyrode solution was complete by 30 min and was proportional to the concentration incubated and non-saturable. Evidence for a reversible interaction was obtained at earlier time periods. Firmly bound phenoxybenzamine was found mainly in the supernatant (105,000 times g) of platelet homogenates. Small amounts were also detected in the 10,000 times g pellet. The labelled material in the supernatant fraction appeared to have a molecular weight of 500,000 as indicated by gel column chromatography. It was non-dialyzable, precipitated by 40-80% ammonium sulfate, and was absent in smooth muscle from the vas deferens. The material was found to bind norephinephrine but did not alter platelet aggregation. A platelet thrombosthenin fraction but not albumin or platelet fibrinogen bound phenoxybenzamine and had properties similar to the material in the supernatant fraction. The relationship of the phenoxybenzamine-binding material to thrombosthenin is discussed.", "contents": "Binding of phenoxybenzamine to rat platelets and platelet fractions. Irreversible binding of labelled phenoxybenzamine to platelets suspended in Tyrode solution was complete by 30 min and was proportional to the concentration incubated and non-saturable. Evidence for a reversible interaction was obtained at earlier time periods. Firmly bound phenoxybenzamine was found mainly in the supernatant (105,000 times g) of platelet homogenates. Small amounts were also detected in the 10,000 times g pellet. The labelled material in the supernatant fraction appeared to have a molecular weight of 500,000 as indicated by gel column chromatography. It was non-dialyzable, precipitated by 40-80% ammonium sulfate, and was absent in smooth muscle from the vas deferens. The material was found to bind norephinephrine but did not alter platelet aggregation. A platelet thrombosthenin fraction but not albumin or platelet fibrinogen bound phenoxybenzamine and had properties similar to the material in the supernatant fraction. The relationship of the phenoxybenzamine-binding material to thrombosthenin is discussed."} {"id": "PMID:168088", "title": "Papaverine, cyclic AMP and the dependence of the rat aorta on extracellular calcium.", "content": "The spasmolytic effects of papaverine and dibutyryl cyclic AMP (db-cAMP) were compared on isometric contractile responses induced by addition of increasing amounts of external calcium to K+-depolarized or noradrenaline-stimulated rat aorta strips. Papaverine at a concentration active on depolarized strips (3 times 10(-5) moles/1) reduced the maximal contraction (Emax) elicited by Ca2+ in these preparations, while db-cAMP did not. Contrary to what was observed on depolarized aortae, the degree of inhibition of noradrenaline-stimulated strips did not decrease with increasing extracellular calcium concentration (Ca)e. Both db-cAMP and papaverine at a concentration which did not depress Emax (5 times 10(-6) moles/1) potentiated the relaxing effect of high (Ca)e on contractions elicited by noradrenaline. In conclusion, cyclic AMP is probably implicated in the mode of action of papaverine on the noradrenaline-stimulated rat aorta. At a concentration active on depolarized strips, papaverine is also able to impair contractility directly.", "contents": "Papaverine, cyclic AMP and the dependence of the rat aorta on extracellular calcium. The spasmolytic effects of papaverine and dibutyryl cyclic AMP (db-cAMP) were compared on isometric contractile responses induced by addition of increasing amounts of external calcium to K+-depolarized or noradrenaline-stimulated rat aorta strips. Papaverine at a concentration active on depolarized strips (3 times 10(-5) moles/1) reduced the maximal contraction (Emax) elicited by Ca2+ in these preparations, while db-cAMP did not. Contrary to what was observed on depolarized aortae, the degree of inhibition of noradrenaline-stimulated strips did not decrease with increasing extracellular calcium concentration (Ca)e. Both db-cAMP and papaverine at a concentration which did not depress Emax (5 times 10(-6) moles/1) potentiated the relaxing effect of high (Ca)e on contractions elicited by noradrenaline. In conclusion, cyclic AMP is probably implicated in the mode of action of papaverine on the noradrenaline-stimulated rat aorta. At a concentration active on depolarized strips, papaverine is also able to impair contractility directly."} {"id": "PMID:168091", "title": "Central and peripheral contribution to the antihypertensive action of indoramin.", "content": "Indoramin has been reported to reduce blood pressure in experimental animals and humans. The complex pharmacological profile of the compound suggests that it may also exert central actions. Effects on spontaneous sympathetic outflow and on sympathetic nerve and blood pressure responses to hypothalamic stimulation were examined in anesthetized cats in the present study. At a low dose (1 mg/kg) indoramin reduced blood pressure but did not significantly influence the level of efferent sympathetic nerve activity. A higher dose (5 mg/kg) lowered pressure further and inhibited activity in the splanchnic, cardiac and renal nerves indicating that reduced sympathetic outflow is a contributing factor to the hypotensive response at this dose. However, in contrast to other centrally acting antihypertensive agents, e.g., clonidine, indoramin did not inhibit the increase in sympathetic nerve activity produced by hypothalamic stimulation.", "contents": "Central and peripheral contribution to the antihypertensive action of indoramin. Indoramin has been reported to reduce blood pressure in experimental animals and humans. The complex pharmacological profile of the compound suggests that it may also exert central actions. Effects on spontaneous sympathetic outflow and on sympathetic nerve and blood pressure responses to hypothalamic stimulation were examined in anesthetized cats in the present study. At a low dose (1 mg/kg) indoramin reduced blood pressure but did not significantly influence the level of efferent sympathetic nerve activity. A higher dose (5 mg/kg) lowered pressure further and inhibited activity in the splanchnic, cardiac and renal nerves indicating that reduced sympathetic outflow is a contributing factor to the hypotensive response at this dose. However, in contrast to other centrally acting antihypertensive agents, e.g., clonidine, indoramin did not inhibit the increase in sympathetic nerve activity produced by hypothalamic stimulation."} {"id": "PMID:168089", "title": "Influence of atropine, metiamide and vagotomy on cAMP of resting and stimulated gastric mucosa.", "content": "In normal rats the effect of atropine and metiamide was studied on cAMP levels of resting and histamine-, pentagastrin-, carbachol- and insulin-stimulated gastric mucosa. In vagotomized rats gastric mucosal cAMP levels were investigated under basal conditions and after insulin. Atropine and metiamide did not alter cAMP levels of resting gastric mucosa. Truncal vagotomy caused an increase in gastric mucosal cAMP, which was not affected by insulin. All gastric secretagogues caused a significant rise in gastric mucosal cAMP levels, which was not antagonized by atropine. Metiamide effectively blocked the rise in cAMP concentration after histamine and pentagastrin, but not that evoked by cholinergic stimulation. The results are consistent with the view that the in vivo rise of gastric mucosal cAMP after carbachol or insulin is not due to a direct cholinergic action. From the spectrum of inhibitory actions of metiamide it looks as if the increase in rat gastric mucosal cAMP concentration after histamine and pentagastrin administration is mediated by H2-receptor stimulation.", "contents": "Influence of atropine, metiamide and vagotomy on cAMP of resting and stimulated gastric mucosa. In normal rats the effect of atropine and metiamide was studied on cAMP levels of resting and histamine-, pentagastrin-, carbachol- and insulin-stimulated gastric mucosa. In vagotomized rats gastric mucosal cAMP levels were investigated under basal conditions and after insulin. Atropine and metiamide did not alter cAMP levels of resting gastric mucosa. Truncal vagotomy caused an increase in gastric mucosal cAMP, which was not affected by insulin. All gastric secretagogues caused a significant rise in gastric mucosal cAMP levels, which was not antagonized by atropine. Metiamide effectively blocked the rise in cAMP concentration after histamine and pentagastrin, but not that evoked by cholinergic stimulation. The results are consistent with the view that the in vivo rise of gastric mucosal cAMP after carbachol or insulin is not due to a direct cholinergic action. From the spectrum of inhibitory actions of metiamide it looks as if the increase in rat gastric mucosal cAMP concentration after histamine and pentagastrin administration is mediated by H2-receptor stimulation."} {"id": "PMID:168090", "title": "Regional cyclic GMP content in incubated tissue slices of rat brain.", "content": "Incubated tissue slices from different regions of the rat brain contained cyclic guanosine 3',5'-monophosphate (cyclic GMP) in the following descending order of content: cerebellum greater than hypothalamus greater than striatum greater than thalamusmidbrain greater than brain stem greater that hippocampus greater than cerebral cortex. Cholinomimetic agents at 10(-5) M (carbamylcholine, pilocarpine, acetylcholine and eserine) and papavering at 14(-4) M significantly elevated cyclic GMP accumulation in the cerebral cortex. Three min incubation with carbamylcholine (10(-5) M) did not increase cyclic nucleotide accumulation in the remaining brain regions.", "contents": "Regional cyclic GMP content in incubated tissue slices of rat brain. Incubated tissue slices from different regions of the rat brain contained cyclic guanosine 3',5'-monophosphate (cyclic GMP) in the following descending order of content: cerebellum greater than hypothalamus greater than striatum greater than thalamusmidbrain greater than brain stem greater that hippocampus greater than cerebral cortex. Cholinomimetic agents at 10(-5) M (carbamylcholine, pilocarpine, acetylcholine and eserine) and papavering at 14(-4) M significantly elevated cyclic GMP accumulation in the cerebral cortex. Three min incubation with carbamylcholine (10(-5) M) did not increase cyclic nucleotide accumulation in the remaining brain regions."} {"id": "PMID:168096", "title": "The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat.", "content": "The effects of microelectrophoretic strychnine and bicuculline methochloride were studied on the time course of synaptic inhibitions of single dorsal horn neurones in the lumbar spinal cord of cats anaesthetized with pentobarbitone. The inhibitions, evoked by volleys in mixed myelinated cutaneous afferents, varied in latency and duration. In general, early inhibitions (latency less than 12msec; duration less than 36 msec) were reduced by microelectrophoretic strychnine whereas late inhibitions (latency more than 16 msec and more prolonged in duration) were usually sensitive to bicuculline. These results can be interpreted in terms of glycine and GABA as the inh ibitory transmitters of early and late inhibitions respectively.", "contents": "The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat. The effects of microelectrophoretic strychnine and bicuculline methochloride were studied on the time course of synaptic inhibitions of single dorsal horn neurones in the lumbar spinal cord of cats anaesthetized with pentobarbitone. The inhibitions, evoked by volleys in mixed myelinated cutaneous afferents, varied in latency and duration. In general, early inhibitions (latency less than 12msec; duration less than 36 msec) were reduced by microelectrophoretic strychnine whereas late inhibitions (latency more than 16 msec and more prolonged in duration) were usually sensitive to bicuculline. These results can be interpreted in terms of glycine and GABA as the inh ibitory transmitters of early and late inhibitions respectively."} {"id": "PMID:168098", "title": "Effect of hypoxia on the cerebral energy state.", "content": "The effect of hypoxia on glycogen content, adenyl cyclase activity, cyclic 3',5'-AMP concentration, lactate: pyruvate ratio and the energy charge potential connected with the pool of adenylates was evaluated in the motor area of the cortex of beagle dogs. At first, controlled hypoxia induces activation of the adenyl cyclase system while subsequently, with PaO2 values lower than 20 mm Hg, a depression of the system is observed simultaneously with a drop of the energy charge potential. When normal oxygenation is resumed, the biochemical parameters examined tend to go back to normal even though it is still necessary to resort to anaerobic mechanisms. The intracarotid perfusion with nicergoline enhances the post-hypoxic recovery of adenyl cyclase activity, even though the ergoline derivative is inactive during the stages of hypoxic suffering of the brain studied in the present work.", "contents": "Effect of hypoxia on the cerebral energy state. The effect of hypoxia on glycogen content, adenyl cyclase activity, cyclic 3',5'-AMP concentration, lactate: pyruvate ratio and the energy charge potential connected with the pool of adenylates was evaluated in the motor area of the cortex of beagle dogs. At first, controlled hypoxia induces activation of the adenyl cyclase system while subsequently, with PaO2 values lower than 20 mm Hg, a depression of the system is observed simultaneously with a drop of the energy charge potential. When normal oxygenation is resumed, the biochemical parameters examined tend to go back to normal even though it is still necessary to resort to anaerobic mechanisms. The intracarotid perfusion with nicergoline enhances the post-hypoxic recovery of adenyl cyclase activity, even though the ergoline derivative is inactive during the stages of hypoxic suffering of the brain studied in the present work."} {"id": "PMID:168099", "title": "Immediate effect of prostaglandin F2alpha during the luteal phase of the menstrual cycle.", "content": "Serum luteinizing hormone, estradiol, 17-hydroxyprogesterone, and progesterone determinations were performed in five normally ovulating women prior to, during, and after prostaglandin F2alpha (PGF2alpha was infusion. A total of 75 mg of PGF2alpha was infused over 48 hours, beginning on the 4th day of the luteal phase. Endometrial biopsies were obtained at the completion of the infusion. In all patients, transient decreases in serum progesterone and 17-hydroxyprogesterone levels were observed during PGF2alpha infusion. Subsequent rises in the serum progesterone and 17-hydroxyprogesterone levels were observed 24 hours after completion of the infusion. There was no significant change in serum luteinizing hormone levels. Premature menstrual bleeding occurred with 24 to 72 hours after the termination of the infusion, while progesterone and 17-hydroxyprogesterone levels were still elevated. Endometrial histology revealed focal stromal necrosis in the presence of the normal secretory endometrium. It is concluded that, in the human, PGF2alpha at this dose and time schedule is not luteolytic.", "contents": "Immediate effect of prostaglandin F2alpha during the luteal phase of the menstrual cycle. Serum luteinizing hormone, estradiol, 17-hydroxyprogesterone, and progesterone determinations were performed in five normally ovulating women prior to, during, and after prostaglandin F2alpha (PGF2alpha was infusion. A total of 75 mg of PGF2alpha was infused over 48 hours, beginning on the 4th day of the luteal phase. Endometrial biopsies were obtained at the completion of the infusion. In all patients, transient decreases in serum progesterone and 17-hydroxyprogesterone levels were observed during PGF2alpha infusion. Subsequent rises in the serum progesterone and 17-hydroxyprogesterone levels were observed 24 hours after completion of the infusion. There was no significant change in serum luteinizing hormone levels. Premature menstrual bleeding occurred with 24 to 72 hours after the termination of the infusion, while progesterone and 17-hydroxyprogesterone levels were still elevated. Endometrial histology revealed focal stromal necrosis in the presence of the normal secretory endometrium. It is concluded that, in the human, PGF2alpha at this dose and time schedule is not luteolytic."} {"id": "PMID:168100", "title": "[Effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)].", "content": "Isolated adrenal cells were obtained surgically from patients with primary aldosteronism, breast cancer, or Cushing's syndrome. They were prepared by the modification of Sayers method, and incubated at 37 degrees C for 2 hours under 95% O-2-5% CO-2, in the medium of calcium-free Krebs-Ringer bicarbonate buffer containing 0.2% glucose and 0.5% bovine serum albumin, to which various doses of calcium, ACTH, dibutyryl cyclic AMP or cycloheximide were added. Steroid production was measured by the method of Silber et al. In isolated normal adrenocortical cells, 11-OHCS was produced by calcium alone in the absence of ACTH or dibutyryl cyclic AMP, while it was not produced by ACTH alone without calcium. 11-OHCS production by ACTH was decreased in the high concentration of calcium (10.16 mM, 12.70 mM). Cycloheximide partially blocked an increase in 11-OHCS synthesis induced by calcium. These data suggest that adenyl cyclase of human adrenocortical cells may be stimulated by calcium alone, supporting the notion that calcium is a second messenger. The ratio of 11-OHCS production by calcium alone to that by dibutyryl cyclic AMP was higher in adenoma cells than in normal cells. This may account for the character of autonomic steroid production in adrenocortical adenoma cells.", "contents": "[Effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)]. Isolated adrenal cells were obtained surgically from patients with primary aldosteronism, breast cancer, or Cushing's syndrome. They were prepared by the modification of Sayers method, and incubated at 37 degrees C for 2 hours under 95% O-2-5% CO-2, in the medium of calcium-free Krebs-Ringer bicarbonate buffer containing 0.2% glucose and 0.5% bovine serum albumin, to which various doses of calcium, ACTH, dibutyryl cyclic AMP or cycloheximide were added. Steroid production was measured by the method of Silber et al. In isolated normal adrenocortical cells, 11-OHCS was produced by calcium alone in the absence of ACTH or dibutyryl cyclic AMP, while it was not produced by ACTH alone without calcium. 11-OHCS production by ACTH was decreased in the high concentration of calcium (10.16 mM, 12.70 mM). Cycloheximide partially blocked an increase in 11-OHCS synthesis induced by calcium. These data suggest that adenyl cyclase of human adrenocortical cells may be stimulated by calcium alone, supporting the notion that calcium is a second messenger. The ratio of 11-OHCS production by calcium alone to that by dibutyryl cyclic AMP was higher in adenoma cells than in normal cells. This may account for the character of autonomic steroid production in adrenocortical adenoma cells."} {"id": "PMID:168101", "title": "Calcium requirement for stimulation of cyclic AMP accumulation in anterior pituitary gland by LH-RH.", "content": "Removal of Ca2+ from the incubation medium by addition of 2 mM ethylene glycol bis-(beta-aminoethyl ether)-N, N'tetraacetic acid (EGTA) leads to at least 75% inhibition of the luteinizing hormone-releasing hormone (LH-RH)-induced accululation of adenosine 3'5'-monophoshpate (cyclic AMP) in rat anterior pituitary gland in vitro. This inhibitory effect of EGTA is reversed by the addition of Ca2+. A half-maximal effect of Ca2+ on LH-RH--induced cyclic AMP accumulation is observed at 2-5 X 10-5 M free Ca2+. The LH-RH-induced LH and FSH release is completely dependent upon the presence of Ca2+ in the incubation medium, a half-maximal effect being measured at 1-2 X 10-4 M free Ca2+. The basal release release of LH is increased upon Ca2+ removal.", "contents": "Calcium requirement for stimulation of cyclic AMP accumulation in anterior pituitary gland by LH-RH. Removal of Ca2+ from the incubation medium by addition of 2 mM ethylene glycol bis-(beta-aminoethyl ether)-N, N'tetraacetic acid (EGTA) leads to at least 75% inhibition of the luteinizing hormone-releasing hormone (LH-RH)-induced accululation of adenosine 3'5'-monophoshpate (cyclic AMP) in rat anterior pituitary gland in vitro. This inhibitory effect of EGTA is reversed by the addition of Ca2+. A half-maximal effect of Ca2+ on LH-RH--induced cyclic AMP accumulation is observed at 2-5 X 10-5 M free Ca2+. The LH-RH-induced LH and FSH release is completely dependent upon the presence of Ca2+ in the incubation medium, a half-maximal effect being measured at 1-2 X 10-4 M free Ca2+. The basal release release of LH is increased upon Ca2+ removal."} {"id": "PMID:168102", "title": "Testicular androgen-binding protein (ABP): comparison of ABP in rabbit testis and epididymis with a similar androgen-binding protein (TeBG) in rabbit serum.", "content": "Testicular androgen-binding proteins (ABP) in rabbit testis, caput epididymis and efferent duct fluid (EDF) were compared to a similar androgen-binding protein TeBg) in rabbit serum. The affinity of these proteins for 5alpha-dihydrotesterone (DHT) at 0 degrees C (KaABP = 1.6 X 10(9) M-1 and KaTeBG = 1.9 X 10(9) M-1) and their steroid specificities were similar (DHT greater than androstanediol greater than progesterone and androstenedione). ABP and TeBG had also almost identical Stokes radii (42.8 +/- 1.2 and 43.9 +- 0.8 A, respectively), sedimentation coefficients (4.7 +/- 0.2 S and 4.4 +/- 0.2 S, respectively) and electrophoretic mobility (Rf = 0.4 in 6 1/2% polyacrylamide gels). Calculation of molecular weights from Stokes radii and sedimentation rates indicated a molecular weight of 74,000 (69,000-78,000) for TeBG and 76,000 (71,000-82,000) for ABP. The corresponding frictional ratios were 1.61 for TeBG and 1.55 for ABP assuming a partial specific volume (v) of 0.70 cm3/g. Polyacrylamide gel electrophoresis (PAGE) at different gel concentrations gave a mean molecular radius of 2.74 nm, also indicating a molecular weight of about 75,000 (v = 0.70 cm3/g. ABP and TeBG could not be separated by PAGE; however, partial separation of ABP and TeBG was achieved by isoelectric focusing and ion-exchange chromatography on DEAE-cellulose. TeBG focused at pH 5.4, whereas ABP formed a distinct peak of bound radioactivity at pH 4.7. Also by ionexchange chromatography, ABP in both testis and epididymal supernatants was shown to have an apparently higher surface charge than TeBG in rabbit serum. The concentration of ABP in efferent duct fluid (2 X 10(-7) M = 60 pmol/mg protien) was much higher than TeBG in male rabbit serum (5.2 X 10(-8) M = 0.7 pmol/mg protein). These findings ruled against the possibility that ABP in the testis and epididymis could have been derived directly from serum. It is concluded that ABP and TeBG are very similar if not identical proteins both serving as transport and carrier proteins in their respective compartments.", "contents": "Testicular androgen-binding protein (ABP): comparison of ABP in rabbit testis and epididymis with a similar androgen-binding protein (TeBG) in rabbit serum. Testicular androgen-binding proteins (ABP) in rabbit testis, caput epididymis and efferent duct fluid (EDF) were compared to a similar androgen-binding protein TeBg) in rabbit serum. The affinity of these proteins for 5alpha-dihydrotesterone (DHT) at 0 degrees C (KaABP = 1.6 X 10(9) M-1 and KaTeBG = 1.9 X 10(9) M-1) and their steroid specificities were similar (DHT greater than androstanediol greater than progesterone and androstenedione). ABP and TeBG had also almost identical Stokes radii (42.8 +/- 1.2 and 43.9 +- 0.8 A, respectively), sedimentation coefficients (4.7 +/- 0.2 S and 4.4 +/- 0.2 S, respectively) and electrophoretic mobility (Rf = 0.4 in 6 1/2% polyacrylamide gels). Calculation of molecular weights from Stokes radii and sedimentation rates indicated a molecular weight of 74,000 (69,000-78,000) for TeBG and 76,000 (71,000-82,000) for ABP. The corresponding frictional ratios were 1.61 for TeBG and 1.55 for ABP assuming a partial specific volume (v) of 0.70 cm3/g. Polyacrylamide gel electrophoresis (PAGE) at different gel concentrations gave a mean molecular radius of 2.74 nm, also indicating a molecular weight of about 75,000 (v = 0.70 cm3/g. ABP and TeBG could not be separated by PAGE; however, partial separation of ABP and TeBG was achieved by isoelectric focusing and ion-exchange chromatography on DEAE-cellulose. TeBG focused at pH 5.4, whereas ABP formed a distinct peak of bound radioactivity at pH 4.7. Also by ionexchange chromatography, ABP in both testis and epididymal supernatants was shown to have an apparently higher surface charge than TeBG in rabbit serum. The concentration of ABP in efferent duct fluid (2 X 10(-7) M = 60 pmol/mg protien) was much higher than TeBG in male rabbit serum (5.2 X 10(-8) M = 0.7 pmol/mg protein). These findings ruled against the possibility that ABP in the testis and epididymis could have been derived directly from serum. It is concluded that ABP and TeBG are very similar if not identical proteins both serving as transport and carrier proteins in their respective compartments."} {"id": "PMID:168103", "title": "The metabolism of luteinizing hormone. Plasma clearance, urinary excretion, and tissue uptake.", "content": "The kinetics of plasma clearance, tissue uptake, and urinary excretion of tritiated ovine pituitary luteinizing hormone in adult male rats are reported. Most of the intravenously injected tritiated gonadotropin is cleared from circulation with a half-life of five minutes, and this is independent of the injected amount of hormone over a wide dose range. It was found that the hormone is rapidly removed from circulation by the kidneys, probably by glomerular filtration, and excreted in the urine. The radioactivity present in the urine is associated with material of the same molecular size as the native hormone and, moreover, the urinary hormone retains a significant amount of biological activity. A small amount of the hormone is catabolized by the kidney and liver, and our data suggest that this occurs in the cortex and hepatocytes, respectively.", "contents": "The metabolism of luteinizing hormone. Plasma clearance, urinary excretion, and tissue uptake. The kinetics of plasma clearance, tissue uptake, and urinary excretion of tritiated ovine pituitary luteinizing hormone in adult male rats are reported. Most of the intravenously injected tritiated gonadotropin is cleared from circulation with a half-life of five minutes, and this is independent of the injected amount of hormone over a wide dose range. It was found that the hormone is rapidly removed from circulation by the kidneys, probably by glomerular filtration, and excreted in the urine. The radioactivity present in the urine is associated with material of the same molecular size as the native hormone and, moreover, the urinary hormone retains a significant amount of biological activity. A small amount of the hormone is catabolized by the kidney and liver, and our data suggest that this occurs in the cortex and hepatocytes, respectively."} {"id": "PMID:168104", "title": "Effects of follicle-stimulating hormone on cultures of Sertoli cell preparations.", "content": "Sertoli cell-enriched preparations were obtained by sequential enzyme treatment of testes of 18-20 day old rats, and were maintained in culture in a chemically defined medium. The addition of highly purified follicle-stimulating hormone (FSH) to cells immediately after preparation, or after 48 h in culture, elicited an increase in the level of cyclic adenosine 3',5'-monophosphate (cAMP) when incubated in the presence of 3-isobutyl-1-methylxanthine (MIX). Luteinizing hormone (LH) had no effect on the cAMP levels. The cells cultured in the presence of FSH or dibutyryl cAMP for 48 h incorporated more [3H]leucine into trichloroacetic acid (TCA)-insoluble material than did cells cultured in the basal medium. Cycloheximide abolished the amino acid incorporation into protein precipitated by TCA. The data demonstrate that the Sertoli cell is a target cell for FSH action, and indicate that added dibutyryl cAMP can duplicate the enhancement of amino acid incorporation into protein elicited by FSH.", "contents": "Effects of follicle-stimulating hormone on cultures of Sertoli cell preparations. Sertoli cell-enriched preparations were obtained by sequential enzyme treatment of testes of 18-20 day old rats, and were maintained in culture in a chemically defined medium. The addition of highly purified follicle-stimulating hormone (FSH) to cells immediately after preparation, or after 48 h in culture, elicited an increase in the level of cyclic adenosine 3',5'-monophosphate (cAMP) when incubated in the presence of 3-isobutyl-1-methylxanthine (MIX). Luteinizing hormone (LH) had no effect on the cAMP levels. The cells cultured in the presence of FSH or dibutyryl cAMP for 48 h incorporated more [3H]leucine into trichloroacetic acid (TCA)-insoluble material than did cells cultured in the basal medium. Cycloheximide abolished the amino acid incorporation into protein precipitated by TCA. The data demonstrate that the Sertoli cell is a target cell for FSH action, and indicate that added dibutyryl cAMP can duplicate the enhancement of amino acid incorporation into protein elicited by FSH."} {"id": "PMID:168106", "title": "The excretion of proinsulin and insulin in urine.", "content": "Proinsulin-like components (PLC) and insulin have been measured in 24 hr urine samples from 8 healthy subjects. The mean excretion of PLC was 45.8 ng and that of insulin 314 ng; the PLC: insulin ratio was 0.14. Urinary PLC was increased 3.5 fold in a patient with a pancreatic islet cell tumor and the PLC: insulin ratio was 0.35. The urinary PLC: insulin ratio is lower than that of serum, presumably because of the relatively lower urinary clearance of the larger molecular weight PLC.", "contents": "The excretion of proinsulin and insulin in urine. Proinsulin-like components (PLC) and insulin have been measured in 24 hr urine samples from 8 healthy subjects. The mean excretion of PLC was 45.8 ng and that of insulin 314 ng; the PLC: insulin ratio was 0.14. Urinary PLC was increased 3.5 fold in a patient with a pancreatic islet cell tumor and the PLC: insulin ratio was 0.35. The urinary PLC: insulin ratio is lower than that of serum, presumably because of the relatively lower urinary clearance of the larger molecular weight PLC."} {"id": "PMID:168107", "title": "The effect of phenformin upon the plasma pancreatic and gut glucagon-like immunoreactivity in diabetics.", "content": "Five patients with mild maturity-onset diabetes were given 250 ml of a 20% glucose solution by intraduodenal infusion and eight other patients similarly received an amino acid solution in a dose of 0.5 g amino acids per kg body weight. The pancreatic and gut glucagon-like immunoreactivity (pancreatic GLI and gut GLI) in plasma were measured before and after the application of the two stimuli. Each person was tested twice; the first (control) test was followed by a second test after three days of treatment with phenformin 150 mg daily, plus the same 150 mg dose taken 60 min before the intubation. The plasma pancreatic GLI increased slightly during both infusions, but was not affected by phenformin. Intraduodenal infusion of both glucose and the amino acid solution induced a greater rise in plasma gut GLI. After treatment with phenformin, the fasting plasma gut GLI was higher than the control value in eleven of thirteen patients. In most cases higher gut GLI plasma levels were also found after duodenal administration of glucose and amino acids. These data furnish further evidence of the local action of antidiabetic biguanides on the intestinal wall, including its hormonal activity. The hypothesis is advanced that the phenformin-induced increase in gut GLI secretion may bring about competition of the latter with pancreatic glucagon for receptors in liver cell membranes, reducing the effect of glucagon on the liver, and thus contributing to a decrease in glycaemia.", "contents": "The effect of phenformin upon the plasma pancreatic and gut glucagon-like immunoreactivity in diabetics. Five patients with mild maturity-onset diabetes were given 250 ml of a 20% glucose solution by intraduodenal infusion and eight other patients similarly received an amino acid solution in a dose of 0.5 g amino acids per kg body weight. The pancreatic and gut glucagon-like immunoreactivity (pancreatic GLI and gut GLI) in plasma were measured before and after the application of the two stimuli. Each person was tested twice; the first (control) test was followed by a second test after three days of treatment with phenformin 150 mg daily, plus the same 150 mg dose taken 60 min before the intubation. The plasma pancreatic GLI increased slightly during both infusions, but was not affected by phenformin. Intraduodenal infusion of both glucose and the amino acid solution induced a greater rise in plasma gut GLI. After treatment with phenformin, the fasting plasma gut GLI was higher than the control value in eleven of thirteen patients. In most cases higher gut GLI plasma levels were also found after duodenal administration of glucose and amino acids. These data furnish further evidence of the local action of antidiabetic biguanides on the intestinal wall, including its hormonal activity. The hypothesis is advanced that the phenformin-induced increase in gut GLI secretion may bring about competition of the latter with pancreatic glucagon for receptors in liver cell membranes, reducing the effect of glucagon on the liver, and thus contributing to a decrease in glycaemia."} {"id": "PMID:168108", "title": "Diurnal and seasonal variation in oral glucose tolerance: studies in the Antarctic.", "content": "Oral glucose tolerance tests were performed in 12 young men in the Antarctic. Tests were done in the morning and afternoon at three monthly intervals (March, June, September, December). The characteristic diurnal variation in glucose tolerance persisted throughout the year, but was greater in the warmer months (March and December). There were significant seasonal differences in glucose tolerance; blood glucose values were lowest, both morning and afternoon, in December (midsummer). In one pair of tests performed during a reversal of normal sleep/activity pattern, the direction of the normal diurnal variation of glucose tolerance was also reversed.", "contents": "Diurnal and seasonal variation in oral glucose tolerance: studies in the Antarctic. Oral glucose tolerance tests were performed in 12 young men in the Antarctic. Tests were done in the morning and afternoon at three monthly intervals (March, June, September, December). The characteristic diurnal variation in glucose tolerance persisted throughout the year, but was greater in the warmer months (March and December). There were significant seasonal differences in glucose tolerance; blood glucose values were lowest, both morning and afternoon, in December (midsummer). In one pair of tests performed during a reversal of normal sleep/activity pattern, the direction of the normal diurnal variation of glucose tolerance was also reversed."} {"id": "PMID:168109", "title": "Effect of hypophysectomy on protein synthetic-activity of free and bound hepatic ribosomes from insulin-deficient rats.", "content": "Acute insulin deficiency in rats results in a decrease in the in vitro protein synthetic activity of isolated hepatic membrane-bound ribosomes and an increase in activity of free ribosomes. These changes are prevented by concomitant insulin treatment and are reversed by the administration of insulin. The current study evaluated the role of the pituitary in the genesis of these changes. The severity of diabetes produced by streptozotocin was less in hypophysectomized (Hx) rats, and in Hx rats receiving hormone replacement, as compared with similarly streptozotocin-treated intact rats. Although acute insulin deficiency in intact rats produced the previously described increase in protein synthetic activity of free hepatic ribosomes and decrease in activity of hepatic bound ribosomes, these changes did not occur in Hx rats, even when Hx rats received replacement doses of thyroxine, ACTH, and growth hormone. Thus, the changes in hepatic protein synthetic activity that occur in rats with acute experimental diabetes mellitus are secondary to the metabolic sequalae of insulin lack and the response of the pituitary gland to insulin deficiency.", "contents": "Effect of hypophysectomy on protein synthetic-activity of free and bound hepatic ribosomes from insulin-deficient rats. Acute insulin deficiency in rats results in a decrease in the in vitro protein synthetic activity of isolated hepatic membrane-bound ribosomes and an increase in activity of free ribosomes. These changes are prevented by concomitant insulin treatment and are reversed by the administration of insulin. The current study evaluated the role of the pituitary in the genesis of these changes. The severity of diabetes produced by streptozotocin was less in hypophysectomized (Hx) rats, and in Hx rats receiving hormone replacement, as compared with similarly streptozotocin-treated intact rats. Although acute insulin deficiency in intact rats produced the previously described increase in protein synthetic activity of free hepatic ribosomes and decrease in activity of hepatic bound ribosomes, these changes did not occur in Hx rats, even when Hx rats received replacement doses of thyroxine, ACTH, and growth hormone. Thus, the changes in hepatic protein synthetic activity that occur in rats with acute experimental diabetes mellitus are secondary to the metabolic sequalae of insulin lack and the response of the pituitary gland to insulin deficiency."} {"id": "PMID:168110", "title": "A radioreceptor-assay for glucagon: binding of enteroglucagon to liver plasma membranes.", "content": "A radioreceptor-assay for glucagon was developed employing pig liver plasma membranes isolated by means of an aqueous two-phase polymer system. The assay is simple, precise, and has a detection limit of 40 pg/ml. Acid-ethanol extracts of porcine intestinal mucosa and entero-glucagon purified by affinity chromatography interfered strongly with the binding of 125I-labelled glucagon. The affinity of enteroglucagon for the membranes was lower than that of glucagon, but even physiological concentrations of the former interfere with glucagon binding, indicating that enteroglucagon may compete with pancreatic glucagon for binding to the hepatocyte under physiological conditions.", "contents": "A radioreceptor-assay for glucagon: binding of enteroglucagon to liver plasma membranes. A radioreceptor-assay for glucagon was developed employing pig liver plasma membranes isolated by means of an aqueous two-phase polymer system. The assay is simple, precise, and has a detection limit of 40 pg/ml. Acid-ethanol extracts of porcine intestinal mucosa and entero-glucagon purified by affinity chromatography interfered strongly with the binding of 125I-labelled glucagon. The affinity of enteroglucagon for the membranes was lower than that of glucagon, but even physiological concentrations of the former interfere with glucagon binding, indicating that enteroglucagon may compete with pancreatic glucagon for binding to the hepatocyte under physiological conditions."} {"id": "PMID:168111", "title": "Factors governing glucose induced elevation of cyclic 3'5' AMP levels in pancreatic islets.", "content": "Adenosine 3'5'-cyclic monophosphate (cAMP) levels of isolated perifused pancreatic islets were elevated by high levels of glucose concomitantly with initiation of enhanced insulin secretion. The rise of cAMP was biphasic and seemed to be related to the temporal biphasic kinetics of insulin release. However, the temporal profiles of cAMP level changes and of insulin release differed; the major rise of the cAMP levels was seen during the initial phase, whereas insulin secretion was more pronounced during the second phase of release. Glucose-induced cAMP elevation required the presence of extracellular Ca++. Mannoheptulose completely blocked cAMP elevation due to high glucose. Exogenous insulin which has been shown by others to inhibit insulin secretion in vitro, blunted the glucose-induced cAMP rise. These observations and data in the literature are compatible with the concept that under physiological conditions glucose governs the intracellular cAMP levels in a Ca++ dependent manner - either directly or indirectly through metabolic effects.", "contents": "Factors governing glucose induced elevation of cyclic 3'5' AMP levels in pancreatic islets. Adenosine 3'5'-cyclic monophosphate (cAMP) levels of isolated perifused pancreatic islets were elevated by high levels of glucose concomitantly with initiation of enhanced insulin secretion. The rise of cAMP was biphasic and seemed to be related to the temporal biphasic kinetics of insulin release. However, the temporal profiles of cAMP level changes and of insulin release differed; the major rise of the cAMP levels was seen during the initial phase, whereas insulin secretion was more pronounced during the second phase of release. Glucose-induced cAMP elevation required the presence of extracellular Ca++. Mannoheptulose completely blocked cAMP elevation due to high glucose. Exogenous insulin which has been shown by others to inhibit insulin secretion in vitro, blunted the glucose-induced cAMP rise. These observations and data in the literature are compatible with the concept that under physiological conditions glucose governs the intracellular cAMP levels in a Ca++ dependent manner - either directly or indirectly through metabolic effects."} {"id": "PMID:168112", "title": "Relationship between Epstein-Barr virus-associated nuclear antigen and cell viability in human cell lines.", "content": "The relationship between the cell viability and frequency of cell with Epstein-Barr virus (EBV)-associated nuclear antigen was investigated in cultures of 4 EBV-carrier lymphoblastoid cell lines, by means of anti-complement immunofluorescence. The percentages of viable cells and those of EB nuclear antigen-positive cells were close to each other in the entire course of cultivation of all cell lines. This leads to a conclusion that absence of EB nuclear antigen in a given cell population should be evaluated in relation to cell viability.", "contents": "Relationship between Epstein-Barr virus-associated nuclear antigen and cell viability in human cell lines. The relationship between the cell viability and frequency of cell with Epstein-Barr virus (EBV)-associated nuclear antigen was investigated in cultures of 4 EBV-carrier lymphoblastoid cell lines, by means of anti-complement immunofluorescence. The percentages of viable cells and those of EB nuclear antigen-positive cells were close to each other in the entire course of cultivation of all cell lines. This leads to a conclusion that absence of EB nuclear antigen in a given cell population should be evaluated in relation to cell viability."} {"id": "PMID:168113", "title": "A tumor-specific cytotoxic and neutralizing factor in rats immunized with ascites hepatoma induced by azo dyes.", "content": "Transplantation immunity of Donryu rats against ascites hepatoma AH-64A induced by azo dye was demonstrated by intraperitoneal injection of tumor cells pretreated with heteroantibodies in vitro. Hyper-immunity was induced by successive challenges with fresh tumor cells. The cytotoxic effect of the serum of resistant rats (RRS) against AH-64A tumor cells was not reduced after absorption with normal rat liver cells, but was slightly reduced after absorption with normal rat spleen cells. The cytotoxicity was absorbed completely with 5 times 10(6) AH-64A tumor cells. AH-64A, -B, -C, and -D are ascites hepatoma cell lines originating from a single Donryu rat. AH-64A and AH-64B cross-reacted with RRS while AH-64C and AH-64D, chemically induced DBLA-6 leukemia cells and normal lymph node cells of rats, did not react with RRS in indirect immunofluorescence and cytotoxicity tests. A neutralization test was carried out by treating 2 times 10(5) tumor cell with either RRS or immune spleen cell in vitro and then injecting them subcutaneously into irradiated rats (400 R). It was found that 1:20 dilution of RRS protected the rats against AH-64A tumor cell growth while 1:40 and 1:80 dilutions of RRS caused some protection. A subcutaneous tumor mass developed after transplantation of tumor cells treated with RRS, but after about 2 weeks this began to decrease in size and disappeared completely within 6 weeks after transplantation. Treatment of AH-64A tumor cells with immune spleen cells at cell-to-cell ratios of 1:200 and 1:100 caused complete neutralization while normal spleen cells at a ratio of 1:200 had slight effect. Treat;ent with immune spleen cells prevented tumor growth from t;e start. Most of the surviving animals were resistant to c,allenge with 1 times 10(5) fresh AH-64A cells. RRS was fractionated by cellulose acetate membrane electrophoresis and the amounts of beta1- and gamma-globulin fractions were found to be 48 and 42% more than in normal rat serum. The immunoelectrophoretic pattern of resistant rat serum showed a stronger IgM precipitin line than that of normal rat serum.", "contents": "A tumor-specific cytotoxic and neutralizing factor in rats immunized with ascites hepatoma induced by azo dyes. Transplantation immunity of Donryu rats against ascites hepatoma AH-64A induced by azo dye was demonstrated by intraperitoneal injection of tumor cells pretreated with heteroantibodies in vitro. Hyper-immunity was induced by successive challenges with fresh tumor cells. The cytotoxic effect of the serum of resistant rats (RRS) against AH-64A tumor cells was not reduced after absorption with normal rat liver cells, but was slightly reduced after absorption with normal rat spleen cells. The cytotoxicity was absorbed completely with 5 times 10(6) AH-64A tumor cells. AH-64A, -B, -C, and -D are ascites hepatoma cell lines originating from a single Donryu rat. AH-64A and AH-64B cross-reacted with RRS while AH-64C and AH-64D, chemically induced DBLA-6 leukemia cells and normal lymph node cells of rats, did not react with RRS in indirect immunofluorescence and cytotoxicity tests. A neutralization test was carried out by treating 2 times 10(5) tumor cell with either RRS or immune spleen cell in vitro and then injecting them subcutaneously into irradiated rats (400 R). It was found that 1:20 dilution of RRS protected the rats against AH-64A tumor cell growth while 1:40 and 1:80 dilutions of RRS caused some protection. A subcutaneous tumor mass developed after transplantation of tumor cells treated with RRS, but after about 2 weeks this began to decrease in size and disappeared completely within 6 weeks after transplantation. Treatment of AH-64A tumor cells with immune spleen cells at cell-to-cell ratios of 1:200 and 1:100 caused complete neutralization while normal spleen cells at a ratio of 1:200 had slight effect. Treat;ent with immune spleen cells prevented tumor growth from t;e start. Most of the surviving animals were resistant to c,allenge with 1 times 10(5) fresh AH-64A cells. RRS was fractionated by cellulose acetate membrane electrophoresis and the amounts of beta1- and gamma-globulin fractions were found to be 48 and 42% more than in normal rat serum. The immunoelectrophoretic pattern of resistant rat serum showed a stronger IgM precipitin line than that of normal rat serum."} {"id": "PMID:168114", "title": "Antitumor activity of amino acid derivatives in the primary screening.", "content": "Approximately 350 amino acid derivatives were synthesized and tested for antitumor activity in four tumor systems. The effect on life prolongation and tumor growth was examined using mouse leukemia SR-61, Ehrlich ascites carcinoma, ascites sarcoma-180, and rat ascites hepatoma (AH-60C). Among these 350 derivatives, 29 compounds were found to be significantly effective in prolongation of the median life-span and inhibitory effect on tumor growth in the primary screening. Among these 29 compounds, the following five compounds were found to possess potential antitumor activity: N-(2-Naphthalene)sulfonyl-DL-tryptophan (A-91), 2-naphthylaminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), N-9-fluorenylacetyl-L-phenylalanine (A-192), and N-propionyl-L-valine (A-195). These five compounds were active in prolongation of the life-span of mice bearing Ehrlich ascites carcinoma and in the inhibition of the cell growth. Some of these amino acid derivatives inhibited biosynthesis of macromolecules, DNA, RNA, and protein, in tumor cells. These results suggest that the site of action of the five amino acid derivatives appears to result from the inhibition of macromolecules and another unknown mechanism.", "contents": "Antitumor activity of amino acid derivatives in the primary screening. Approximately 350 amino acid derivatives were synthesized and tested for antitumor activity in four tumor systems. The effect on life prolongation and tumor growth was examined using mouse leukemia SR-61, Ehrlich ascites carcinoma, ascites sarcoma-180, and rat ascites hepatoma (AH-60C). Among these 350 derivatives, 29 compounds were found to be significantly effective in prolongation of the median life-span and inhibitory effect on tumor growth in the primary screening. Among these 29 compounds, the following five compounds were found to possess potential antitumor activity: N-(2-Naphthalene)sulfonyl-DL-tryptophan (A-91), 2-naphthylaminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), N-9-fluorenylacetyl-L-phenylalanine (A-192), and N-propionyl-L-valine (A-195). These five compounds were active in prolongation of the life-span of mice bearing Ehrlich ascites carcinoma and in the inhibition of the cell growth. Some of these amino acid derivatives inhibited biosynthesis of macromolecules, DNA, RNA, and protein, in tumor cells. These results suggest that the site of action of the five amino acid derivatives appears to result from the inhibition of macromolecules and another unknown mechanism."} {"id": "PMID:168115", "title": "Effect of steroid hormones on growth of adrenocortical carcinoma transplants in mice;.", "content": "The growth of transplanted carcinomas originating in a gonadectomized C3H male mouse was much faster in intact male mice than in intact or gonadectomized females. Administration of 17beta-estradiol or testosterone propionate in pellets resulted in a marked acceleration of the carcinoma growth in intact female mice. Progesterone and deoxycorticosterone acetate exerted no influence on the carcinoma growth. Neither gonadotropins (pregnant mare's serum gonadotropin plus human chorionic gonadotropin) nor ACTH accelerated the growth. In contrast, cortisone acetate in pellets markedly reduced the growth rate of carcinoma transplants when administered simultaneously with the transplantation. Cortisone acetate also arrested the growth-accelerating effect of 17beta-estradiol on transplanted carcinomas.", "contents": "Effect of steroid hormones on growth of adrenocortical carcinoma transplants in mice;. The growth of transplanted carcinomas originating in a gonadectomized C3H male mouse was much faster in intact male mice than in intact or gonadectomized females. Administration of 17beta-estradiol or testosterone propionate in pellets resulted in a marked acceleration of the carcinoma growth in intact female mice. Progesterone and deoxycorticosterone acetate exerted no influence on the carcinoma growth. Neither gonadotropins (pregnant mare's serum gonadotropin plus human chorionic gonadotropin) nor ACTH accelerated the growth. In contrast, cortisone acetate in pellets markedly reduced the growth rate of carcinoma transplants when administered simultaneously with the transplantation. Cortisone acetate also arrested the growth-accelerating effect of 17beta-estradiol on transplanted carcinomas."} {"id": "PMID:168116", "title": "Combination effect of bis(3-methylsulfonyloxypropyl)amide and 6-mercaptopurine on AH-60C and AH-109A.", "content": "Survival period of rats bearing ascites hepatoma, AH-60C, which was less sensitive to bis (3-methylsulfonyloxypropyl)amine (864-T) and 6-mercaptopurine each alone, was prolonged by the combined treatment with these two agents. Two or 3 rats in groups of 12 animals each survived over 60 days by this combined therapy beginning from day 0. In AH-109A, which was insensitive to 6-mercaptopurine, the group treated with this combination did not survive longer than that with 864-T alone.", "contents": "Combination effect of bis(3-methylsulfonyloxypropyl)amide and 6-mercaptopurine on AH-60C and AH-109A. Survival period of rats bearing ascites hepatoma, AH-60C, which was less sensitive to bis (3-methylsulfonyloxypropyl)amine (864-T) and 6-mercaptopurine each alone, was prolonged by the combined treatment with these two agents. Two or 3 rats in groups of 12 animals each survived over 60 days by this combined therapy beginning from day 0. In AH-109A, which was insensitive to 6-mercaptopurine, the group treated with this combination did not survive longer than that with 864-T alone."} {"id": "PMID:168117", "title": "Heat sensitivity of murine sarcoma virus.", "content": "Murine sarcoma virus (Moloney) was found to be heat labile. Inactivation curve represents a first-order kinetics at temperatures between 30 degrees and 60 degrees. Inactivation constant analysis showed an inflexion at about 45 degrees, and the activation energy was calculated as 67.6 kcal/mol for higher temperature range and 7.95 kcal/mol for lower temperature range. Nature of inactivation is also discussed.", "contents": "Heat sensitivity of murine sarcoma virus. Murine sarcoma virus (Moloney) was found to be heat labile. Inactivation curve represents a first-order kinetics at temperatures between 30 degrees and 60 degrees. Inactivation constant analysis showed an inflexion at about 45 degrees, and the activation energy was calculated as 67.6 kcal/mol for higher temperature range and 7.95 kcal/mol for lower temperature range. Nature of inactivation is also discussed."} {"id": "PMID:168118", "title": "Watery diarrhea associated with pancreatic islet cell carcinoma.", "content": "A patient with severe watery diarrhea and a non-beta islet cell carcinoma of the pancreas producing five hormones (secretin, serotonin, enteroglucagon, vasoactive intestinal polypeptide, and pancreatic glucagon) is described. We have demonstrated massive pancreatic hypersecretion to be a major factor in this patient's diarrhea. Possible inter-relationships of the actions of five hormones present in excess in the patient are discussed.", "contents": "Watery diarrhea associated with pancreatic islet cell carcinoma. A patient with severe watery diarrhea and a non-beta islet cell carcinoma of the pancreas producing five hormones (secretin, serotonin, enteroglucagon, vasoactive intestinal polypeptide, and pancreatic glucagon) is described. We have demonstrated massive pancreatic hypersecretion to be a major factor in this patient's diarrhea. Possible inter-relationships of the actions of five hormones present in excess in the patient are discussed."} {"id": "PMID:168119", "title": "Modulation of stimulated acid secretion by dibutyryl cyclic AMP in the dog stomach.", "content": "An in vivo canine gastric chamber preparation was used to determine effects of exogenous cyclic AMP and dibutyryl cyclic AMP on histamine-driven acid secretion and the role of blood flow in these responses. Histamine was infused intravenously at a submaximal rate 1.2 mu/kg-min) followed by the intraarterial infusion of either cyclic AMP (0.15 mg/kg-min) or dibutyryl cyclic AMP (0.15 mg/kg-min. Acid secretion and mucosal blood flow (aminopyrine clearance) were measured at 15-minute intervals, and electrical potential difference was measured continuously. Histamine alone decreased the potential difference from 82 mV to 48 mV within 60 minutes, increased aminopyrine clearance from 1.0 ml/min to 2.4 ml/min and increased acid output to 220 muEq/15 min. All values returned towards control following termination of histamine infusion. Dibutyryl cyclic AMP significantly increased histamine stimulated acid secretion to 350 muEq/15 min, but did not alter mucosal blood flow or electrical potential. Cyclic AMP did not change secretory, circulatory or electrical response to histamine. Therefore, dibutyryl cyclic AMP appears to increase histamine-stimulated acid secretion, and the effect is not mediated by increased mucosal blood flow.", "contents": "Modulation of stimulated acid secretion by dibutyryl cyclic AMP in the dog stomach. An in vivo canine gastric chamber preparation was used to determine effects of exogenous cyclic AMP and dibutyryl cyclic AMP on histamine-driven acid secretion and the role of blood flow in these responses. Histamine was infused intravenously at a submaximal rate 1.2 mu/kg-min) followed by the intraarterial infusion of either cyclic AMP (0.15 mg/kg-min) or dibutyryl cyclic AMP (0.15 mg/kg-min. Acid secretion and mucosal blood flow (aminopyrine clearance) were measured at 15-minute intervals, and electrical potential difference was measured continuously. Histamine alone decreased the potential difference from 82 mV to 48 mV within 60 minutes, increased aminopyrine clearance from 1.0 ml/min to 2.4 ml/min and increased acid output to 220 muEq/15 min. All values returned towards control following termination of histamine infusion. Dibutyryl cyclic AMP significantly increased histamine stimulated acid secretion to 350 muEq/15 min, but did not alter mucosal blood flow or electrical potential. Cyclic AMP did not change secretory, circulatory or electrical response to histamine. Therefore, dibutyryl cyclic AMP appears to increase histamine-stimulated acid secretion, and the effect is not mediated by increased mucosal blood flow."} {"id": "PMID:168120", "title": "Comparison of metronidazole and chloroquine for the treatment of amoebic liver abscess. A controlled trial.", "content": "Chloroquine and metronidazole were compared in a randomized trial for the treatment of amoebic liver abscess in 36 patients. An additional 30 patients were treated without randomization. Chloroquine was given according to the standard protocol at Los tangeles County-University of Southern California Medical Center, which is 500 mg daily for 10 weeks, whereas metronidazole was given in a dose of 750 mg three times daily for 10 days. Criteria for the diagnosis of amoebic abscess included (a) a suitable clinical picture, (b) filling defect on hepatic scan, (c) high titer of antibody to Entamoeba histolytica by indirect hemagglutination, and (d) eventual complete recovery with treatment or appropriate findings on autopsy examination. Treatment failure, defined as illness that persisted beyond 10 days or recurred after that time, occurred in 1 of 28 patients treated with chloroquine and in 2 of 36 treated with metronidazole. In 2 patients who died it was difficult to assess the result of drug therapy. We conclude that both drugs are highly effective. Metronidazole has the advantage of effectiveness against intestinal amoebiasis and the probability of cure with a shorter course of treatment. Speed of response was slightly greater with metronidazole and was somewhat related to abscess size.", "contents": "Comparison of metronidazole and chloroquine for the treatment of amoebic liver abscess. A controlled trial. Chloroquine and metronidazole were compared in a randomized trial for the treatment of amoebic liver abscess in 36 patients. An additional 30 patients were treated without randomization. Chloroquine was given according to the standard protocol at Los tangeles County-University of Southern California Medical Center, which is 500 mg daily for 10 weeks, whereas metronidazole was given in a dose of 750 mg three times daily for 10 days. Criteria for the diagnosis of amoebic abscess included (a) a suitable clinical picture, (b) filling defect on hepatic scan, (c) high titer of antibody to Entamoeba histolytica by indirect hemagglutination, and (d) eventual complete recovery with treatment or appropriate findings on autopsy examination. Treatment failure, defined as illness that persisted beyond 10 days or recurred after that time, occurred in 1 of 28 patients treated with chloroquine and in 2 of 36 treated with metronidazole. In 2 patients who died it was difficult to assess the result of drug therapy. We conclude that both drugs are highly effective. Metronidazole has the advantage of effectiveness against intestinal amoebiasis and the probability of cure with a shorter course of treatment. Speed of response was slightly greater with metronidazole and was somewhat related to abscess size."} {"id": "PMID:168121", "title": "A controlled evaluation of intravenous adrenocorticotropic hormone and hydrocortisone in the treatment of acute colitis.", "content": "This study compares the efficacy of intravenous adrenocorticotropic hormone (ACTH) with intravenous hydrocortisone in the treatment of patients with symptomatic inflammatory bowel disease. Drug doses were pharmacologically equivalent on the basis of achieved plasma cortisol levels and continuously monitored urinary corticoid excretion rates. Drug selection and patient evaluation were accomplished with a random double blind technique. Evaluation of 22 consecutive hospital patients indicates that ACTH and hydrocortisone, when administered intravenously in pharmacologically equivalent dosage, are therapeutically equivalent, that response to ACTH is rapid, with no therapeutic lag, and that differences in therapeutic responses cannont be corrrelated with differences in systemic steroid levels.", "contents": "A controlled evaluation of intravenous adrenocorticotropic hormone and hydrocortisone in the treatment of acute colitis. This study compares the efficacy of intravenous adrenocorticotropic hormone (ACTH) with intravenous hydrocortisone in the treatment of patients with symptomatic inflammatory bowel disease. Drug doses were pharmacologically equivalent on the basis of achieved plasma cortisol levels and continuously monitored urinary corticoid excretion rates. Drug selection and patient evaluation were accomplished with a random double blind technique. Evaluation of 22 consecutive hospital patients indicates that ACTH and hydrocortisone, when administered intravenously in pharmacologically equivalent dosage, are therapeutically equivalent, that response to ACTH is rapid, with no therapeutic lag, and that differences in therapeutic responses cannont be corrrelated with differences in systemic steroid levels."} {"id": "PMID:168122", "title": "Effects of drugs influencing gastric secretion on the quantitative histological distribution of cyclic adenosine 3':5'-monophosphate in the rat stomach.", "content": "To help clarify conflicting evidence on the cyclic adenosine 3':5'-monophosphate (cyclic AMP) role in acid secretion in the rat stomach, and to establish the quantitative effects on cyclic AMP concentrations in histological regions of the glandular stomach of the 24-hr fasted rat of injections of drugs that stimulate or inhibit gastric secretion, the concentrations were measured by the firefly luminescence method using fresh-frozen microtome tissue sections cut serially through the stomach wall. The data are compatible with cyclic AMP involvement in the acid secretion. Parietal-mucous neck cell cyclic AMP levels (3.3,0.11 means, expressed as picomoles per mg of wet weight and picomoles per mug of protein-nitrogen, respectively) were the highest in any region. Pentagastrin or urecholine elevated these values slightly, and theophylline produced greater increases in all regions (parietal-mucous neck cell, 5.4, 0.22), but theophylline administered either with pentagastrin or urecholine further elevated the values (8.3, 0.31). Urecholine or pentagastrin plus theophylline each generated two approximately equal cyclic AMP concentration peaks (about one-half parietalmucous neck cell concentrations (2.7, 0.22), perhaps by negative feedback, but low dose (2 mg per kg) elevated these values more than pentagastrin or urecholine, and with theophylline they were greatly increased (9.1, 0.32). The inhibitors, atropine and prostaglandin E2, alone or with theophylline, had little influence on parietal-mucous neck cell cyclic AMP levels but caused an increase in chief cell and muscle zones.", "contents": "Effects of drugs influencing gastric secretion on the quantitative histological distribution of cyclic adenosine 3':5'-monophosphate in the rat stomach. To help clarify conflicting evidence on the cyclic adenosine 3':5'-monophosphate (cyclic AMP) role in acid secretion in the rat stomach, and to establish the quantitative effects on cyclic AMP concentrations in histological regions of the glandular stomach of the 24-hr fasted rat of injections of drugs that stimulate or inhibit gastric secretion, the concentrations were measured by the firefly luminescence method using fresh-frozen microtome tissue sections cut serially through the stomach wall. The data are compatible with cyclic AMP involvement in the acid secretion. Parietal-mucous neck cell cyclic AMP levels (3.3,0.11 means, expressed as picomoles per mg of wet weight and picomoles per mug of protein-nitrogen, respectively) were the highest in any region. Pentagastrin or urecholine elevated these values slightly, and theophylline produced greater increases in all regions (parietal-mucous neck cell, 5.4, 0.22), but theophylline administered either with pentagastrin or urecholine further elevated the values (8.3, 0.31). Urecholine or pentagastrin plus theophylline each generated two approximately equal cyclic AMP concentration peaks (about one-half parietalmucous neck cell concentrations (2.7, 0.22), perhaps by negative feedback, but low dose (2 mg per kg) elevated these values more than pentagastrin or urecholine, and with theophylline they were greatly increased (9.1, 0.32). The inhibitors, atropine and prostaglandin E2, alone or with theophylline, had little influence on parietal-mucous neck cell cyclic AMP levels but caused an increase in chief cell and muscle zones."} {"id": "PMID:168123", "title": "Effects of p-chloromercuribenzene sulfonate upon ultrastructure of canine gastric surface cells.", "content": "Exposure of the mucosal surface of exteriorized chambered fundic segments of dog stomach to p-chloromercuribenzene sulfonate (PCMBS) resulted in predictable gross and microscopic structural changes. The first visible response after PCMBS (10 mM) in isosmotic HCl was an intense release of periodic acid-Schiff-stainable mucus. Within 2 min, radioactive PCMBS was found within cells along the entire depth of the gastric glands. Surface cells at 15 min revealed vacuolization of the cell cytoplasm, dilation of the perinuclear and intercellular spaces, mitochondrial swelling, loss of microvilli, and plasmalemma irregularities. Tight junctions, Golgi, and mucous granules appeared unaltered. However, in advanced injury, mucous granules became less dense and their membranes, which were usually smooth, became fragmented and convoluted at this point. Necrotic parietal cells were extruded into the lumen. Damage, however, only rarely extended into the deeper glandular and connective tissue areas.", "contents": "Effects of p-chloromercuribenzene sulfonate upon ultrastructure of canine gastric surface cells. Exposure of the mucosal surface of exteriorized chambered fundic segments of dog stomach to p-chloromercuribenzene sulfonate (PCMBS) resulted in predictable gross and microscopic structural changes. The first visible response after PCMBS (10 mM) in isosmotic HCl was an intense release of periodic acid-Schiff-stainable mucus. Within 2 min, radioactive PCMBS was found within cells along the entire depth of the gastric glands. Surface cells at 15 min revealed vacuolization of the cell cytoplasm, dilation of the perinuclear and intercellular spaces, mitochondrial swelling, loss of microvilli, and plasmalemma irregularities. Tight junctions, Golgi, and mucous granules appeared unaltered. However, in advanced injury, mucous granules became less dense and their membranes, which were usually smooth, became fragmented and convoluted at this point. Necrotic parietal cells were extruded into the lumen. Damage, however, only rarely extended into the deeper glandular and connective tissue areas."} {"id": "PMID:168124", "title": "Effects of cyclic adenosine 3':5'-monophosphate and related agents on acid secretion by isolated rabbit gastric mucosa.", "content": "The effects of various adenosine phosphate compounds, theophylline, histamine,a nd metiamide, on steady rates of acid secretion by isolated fundic mucosa of the rabbit were measured by the pH stat method. Cyclic adenosine 3':5'-monophosphate (cyclic AMP), N(6), O(2')-dibutyryl adenosine 3':5'-monophosphate and theophylline increased the rate of acid secretion. Addition of theophylline in a concentration which has no stimulatory effect, reduces the effective concentrations cyclic AMP or histamine required for stimulation of acid secretion. Measurements of lactate, pyruvate, and CO2 appearances indicated that the increases in acid secretory rates were predominantly due to H+ and not organic acid accumulation in the luminal bath-secretion. Metiamide prevented the stimulatory effects of histamine and ATP. However, metiamide did not prevent the stimulatory effects of N(6),9(2')-dibutyryl adenosine 3':5'-monophosphate, theophylline, or 5'-AMP. The results provide further evidence for a role of cyclic AMP in governing the rate of acid secretion by rabbit stomach. The data also are consistent with histamine and ATP (at least in the concentration used) requiring adenylate cyclase activity for stimulation of acid secretion and 5'-AMP inhibiting phosphodiesterase activity.", "contents": "Effects of cyclic adenosine 3':5'-monophosphate and related agents on acid secretion by isolated rabbit gastric mucosa. The effects of various adenosine phosphate compounds, theophylline, histamine,a nd metiamide, on steady rates of acid secretion by isolated fundic mucosa of the rabbit were measured by the pH stat method. Cyclic adenosine 3':5'-monophosphate (cyclic AMP), N(6), O(2')-dibutyryl adenosine 3':5'-monophosphate and theophylline increased the rate of acid secretion. Addition of theophylline in a concentration which has no stimulatory effect, reduces the effective concentrations cyclic AMP or histamine required for stimulation of acid secretion. Measurements of lactate, pyruvate, and CO2 appearances indicated that the increases in acid secretory rates were predominantly due to H+ and not organic acid accumulation in the luminal bath-secretion. Metiamide prevented the stimulatory effects of histamine and ATP. However, metiamide did not prevent the stimulatory effects of N(6),9(2')-dibutyryl adenosine 3':5'-monophosphate, theophylline, or 5'-AMP. The results provide further evidence for a role of cyclic AMP in governing the rate of acid secretion by rabbit stomach. The data also are consistent with histamine and ATP (at least in the concentration used) requiring adenylate cyclase activity for stimulation of acid secretion and 5'-AMP inhibiting phosphodiesterase activity."} {"id": "PMID:168127", "title": "Epidemiology of herpesvirus and respiratory virus infections. Part 1. Serologic findings.", "content": "The majority of the population group studied had complement-fixation antibodies toward the following viruses: influenza type A, respiratory syncytial, cytomegalovirus, and Epstein-Barr. The herpesvirus infections (cytomegalovirus and Epstein-Barr virus) seemed to be prevalent. Only low incidences of antibodies were found toward adenovirus, influenza type B, influenza type C, and parainfluenza type II. A total of 70 aucte virus infections (increases of antibody titer) were diagnosed in 49 patients. Besides cytomegalovirus, no particular virus infection occurred in a large number. Only 11 of the 70 acute virus infections diagnosed serologically were accompanied by clinical signs of disease", "contents": "Epidemiology of herpesvirus and respiratory virus infections. Part 1. Serologic findings. The majority of the population group studied had complement-fixation antibodies toward the following viruses: influenza type A, respiratory syncytial, cytomegalovirus, and Epstein-Barr. The herpesvirus infections (cytomegalovirus and Epstein-Barr virus) seemed to be prevalent. Only low incidences of antibodies were found toward adenovirus, influenza type B, influenza type C, and parainfluenza type II. A total of 70 aucte virus infections (increases of antibody titer) were diagnosed in 49 patients. Besides cytomegalovirus, no particular virus infection occurred in a large number. Only 11 of the 70 acute virus infections diagnosed serologically were accompanied by clinical signs of disease"} {"id": "PMID:168130", "title": "ACTH-secreting 'apudoma' of gallbladder.", "content": "The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side.", "contents": "ACTH-secreting 'apudoma' of gallbladder. The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side."} {"id": "PMID:168134", "title": "[Sensitivity to noradrenaline and cold tolerance of rats treated chronically with ACTH and adrenocortical hormone (author's transl)].", "content": "Rats treated with ACTH and hydrocortisone for 4 weeks were infused i.v. with noradrenaline or exposed to cold at -15 degrees C for 2 hours, and changes in the rectal temperature and plasma concentrations of NEFA, sugar, and lactate were observed. Rats received single injection of ACTH and hydrocortisone, warm- and cold-acclimated rats were used as controls. In ACTH- and hydrocortisone-treated rats, the noradrenaline infusion caused a significant elevation of the rectal temperature, but lowering of the rectal temperature induced by the acute cold exposure in these treated rats did not differ from the changes in control groups. Moreover, considerable differences were found between these treated rats and cold-acclimated ones in plasma concentrations of NEFA, sugar and lactate after noradrenaline infusion and acute cold exposure. From the results it was inferred that chronic treatment with ACTH and hydrocortisone did not produce similar adaptive metabolic alterations to those found in the course of cold acclimation.", "contents": "[Sensitivity to noradrenaline and cold tolerance of rats treated chronically with ACTH and adrenocortical hormone (author's transl)]. Rats treated with ACTH and hydrocortisone for 4 weeks were infused i.v. with noradrenaline or exposed to cold at -15 degrees C for 2 hours, and changes in the rectal temperature and plasma concentrations of NEFA, sugar, and lactate were observed. Rats received single injection of ACTH and hydrocortisone, warm- and cold-acclimated rats were used as controls. In ACTH- and hydrocortisone-treated rats, the noradrenaline infusion caused a significant elevation of the rectal temperature, but lowering of the rectal temperature induced by the acute cold exposure in these treated rats did not differ from the changes in control groups. Moreover, considerable differences were found between these treated rats and cold-acclimated ones in plasma concentrations of NEFA, sugar and lactate after noradrenaline infusion and acute cold exposure. From the results it was inferred that chronic treatment with ACTH and hydrocortisone did not produce similar adaptive metabolic alterations to those found in the course of cold acclimation."} {"id": "PMID:168138", "title": "Somatostatin-induced inhibition of insulin secretion from isolated islets of rat pancreas in presence of glucagon.", "content": "In order to study the oeffect of somatostatin on the endocrine pancreas directly, islets isolated from rat pancreas by collagenase were incubated for 2 hrs 1) at 50 and 200 mg/100 ml glucose in the absence and presence of somatostatin (1, 10 and 100 mg/ml) and2) at 200 mg/100 ml glucose together with glucagon (5 mug/ml), with or without somatostatin (100 ng/ml). Immunologically measurable insulin was determined in the incubation media at 0, 1 and 2 hrs. Insulin release was not statistically affected by any concentration stomatostatin. On the other hand, somatostatin exerted a significant inhibitory action on glucagon-potentiated insulin secretion (mean +/- SEM, mu1/2 hrs/10 islets: glucose and glucagon: 1253 +/- 92; glucose, glucagon and somatostatin: 786 +/- 76). The insulin output in th epresence of glucose, glucagon and somatostatin was also significantly smaller than in thepresence of glucose alone (1104 +/- 126) or of glucose and somatostatin (1061 +/- 122). The failure of somatostatin to affect glucose-stimulated release of insulin from isolated islets contrasts its inhibitory action on insulin secretion as observed in the isolated perfused pancreas and in vivo. This discrepancy might be ascribed to the isolation procedure using collagenase. However, somatostatin inhibited glucagon-potentiated insulin secretion in isolated islets which resulted in even lower insulin levels than obtained in the parallel experiments without glucagon. It is concluded that the hormone of the alpha cells, or the cyclic AMP system, might play a part in the machanism of somatostatin-induced inhibition of insulin release from the beta-cell.", "contents": "Somatostatin-induced inhibition of insulin secretion from isolated islets of rat pancreas in presence of glucagon. In order to study the oeffect of somatostatin on the endocrine pancreas directly, islets isolated from rat pancreas by collagenase were incubated for 2 hrs 1) at 50 and 200 mg/100 ml glucose in the absence and presence of somatostatin (1, 10 and 100 mg/ml) and2) at 200 mg/100 ml glucose together with glucagon (5 mug/ml), with or without somatostatin (100 ng/ml). Immunologically measurable insulin was determined in the incubation media at 0, 1 and 2 hrs. Insulin release was not statistically affected by any concentration stomatostatin. On the other hand, somatostatin exerted a significant inhibitory action on glucagon-potentiated insulin secretion (mean +/- SEM, mu1/2 hrs/10 islets: glucose and glucagon: 1253 +/- 92; glucose, glucagon and somatostatin: 786 +/- 76). The insulin output in th epresence of glucose, glucagon and somatostatin was also significantly smaller than in thepresence of glucose alone (1104 +/- 126) or of glucose and somatostatin (1061 +/- 122). The failure of somatostatin to affect glucose-stimulated release of insulin from isolated islets contrasts its inhibitory action on insulin secretion as observed in the isolated perfused pancreas and in vivo. This discrepancy might be ascribed to the isolation procedure using collagenase. However, somatostatin inhibited glucagon-potentiated insulin secretion in isolated islets which resulted in even lower insulin levels than obtained in the parallel experiments without glucagon. It is concluded that the hormone of the alpha cells, or the cyclic AMP system, might play a part in the machanism of somatostatin-induced inhibition of insulin release from the beta-cell."} {"id": "PMID:168139", "title": "Studies of the biological activity of insulin, cyclic nucleotides and concanavalin A in the isolated fat cell.", "content": "The insulin or proinsulin response of the isolated rat adipocyte was destroyed by preincubation with trypsin. After 120 minutes, biological responsiveness partially regenerated. Similarly, the biological responsiveness of the isolated fat cell to non-suppressible insulin-like activity (NSILA) was only partially destroyed following trypsin digestion, and did not regenerate. In contrast to the above, cyclic AMP or dibutyryl cyclic AMP effects were unaltered by trypsin or neuraminidase digestion.", "contents": "Studies of the biological activity of insulin, cyclic nucleotides and concanavalin A in the isolated fat cell. The insulin or proinsulin response of the isolated rat adipocyte was destroyed by preincubation with trypsin. After 120 minutes, biological responsiveness partially regenerated. Similarly, the biological responsiveness of the isolated fat cell to non-suppressible insulin-like activity (NSILA) was only partially destroyed following trypsin digestion, and did not regenerate. In contrast to the above, cyclic AMP or dibutyryl cyclic AMP effects were unaltered by trypsin or neuraminidase digestion."} {"id": "PMID:168140", "title": "Effects of glucagon, phosphodiesterase inhibitors, and trypsin treatment on cyclic 3',5' adenosine monophosphate levels in isolated hepatocytes.", "content": "Cyclic 3',5' adenosine monophosphate (cyclic AMP) levels were measured in isolated hepatocytes under several conditions. Following the addition of glucagon cyclic AMP levels increased rapidly with peak values occurring at three minutes. The increase in cyclic AMP was dose dependent. Significant increases were found with 10(-10)M glucagon and a maximum increase of twenty fold was produced by 10(-8) M glucagon. This action of glucagon was augmented by the phosphodiesterase inhibitors, theophylline, SQ 20,009, and papaverine. Treatment of the hepatocytes with trypsin markedly reduced the response to glucagon.", "contents": "Effects of glucagon, phosphodiesterase inhibitors, and trypsin treatment on cyclic 3',5' adenosine monophosphate levels in isolated hepatocytes. Cyclic 3',5' adenosine monophosphate (cyclic AMP) levels were measured in isolated hepatocytes under several conditions. Following the addition of glucagon cyclic AMP levels increased rapidly with peak values occurring at three minutes. The increase in cyclic AMP was dose dependent. Significant increases were found with 10(-10)M glucagon and a maximum increase of twenty fold was produced by 10(-8) M glucagon. This action of glucagon was augmented by the phosphodiesterase inhibitors, theophylline, SQ 20,009, and papaverine. Treatment of the hepatocytes with trypsin markedly reduced the response to glucagon."} {"id": "PMID:168142", "title": "Irreversible inactivation of hypoxanthine phosphoribosyltransferase by periodate oxidized nucleotides.", "content": "Hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) from rat brain or human erytherocytes can be irreversibly inactivated by incubation with periodate-oxidized analogues of the enzyme products GMP or IMP. This inhibition is specific and directed against the product binding site of the enzyme. Inactivation is not produced by periodate-oxidized AMP or other aldehydes, for example periodate-oxidized glycerol. The inactivation is concomitant with the binding of the inhibitor to the enzyme protein. The bound inhibitor cannot be removed from the protein by dialysis, Sephadex chromatography or polyacrylamide-gel electrophoresis. Adenine phosphoribosyltransferase (EC 2.4.2.7), on the other hand, is not influenced by any of the inhibitors mentioned above.", "contents": "Irreversible inactivation of hypoxanthine phosphoribosyltransferase by periodate oxidized nucleotides. Hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) from rat brain or human erytherocytes can be irreversibly inactivated by incubation with periodate-oxidized analogues of the enzyme products GMP or IMP. This inhibition is specific and directed against the product binding site of the enzyme. Inactivation is not produced by periodate-oxidized AMP or other aldehydes, for example periodate-oxidized glycerol. The inactivation is concomitant with the binding of the inhibitor to the enzyme protein. The bound inhibitor cannot be removed from the protein by dialysis, Sephadex chromatography or polyacrylamide-gel electrophoresis. Adenine phosphoribosyltransferase (EC 2.4.2.7), on the other hand, is not influenced by any of the inhibitors mentioned above."} {"id": "PMID:168143", "title": "[Increased estradiol-estrone quotient in rat liver by hydroxysteroids: an effect of the specific hydrogen transfer between steroids].", "content": "After addition of estrone to rat liver slices, a quotient of estradiol/estrone of ca. 0.1 is reached within 1 - 2 min. By additional application of 17 beta-hydroxysteroids this quotient is changed in the direction of estradiol, although the applied concentrations of both steroids are far below the concentration of the cytoplasmic redox couple NADH/NAD. Of all the steroids tested, testosterone had the strongest influence on the quotient, especially in the liver of female rats. This influence is smaller in the livers of male rats and infantile animals. The changing of the E2/E1 quotient by testosterone can be inhibited by the antiandrogen cyproteron acetate. Steroids with hydroxy groups at C-3 or C-20 or high concentrations of non-steroids, which can be oxidized by NAD, change the E2/E1 quotient only minimally. The experiments demonstrate that in liver, the redox couple estradiol/estrone is not in equilibrium with the main redox couple of the cytoplasmic NADH/NAD. Only on account of this fact it is possible that relatively low concentrations of testosterone change the E2/E1 quotient via the C-17 leads to C-17 hydrogen transfer between steroids. Biological consequences are discussed.", "contents": "[Increased estradiol-estrone quotient in rat liver by hydroxysteroids: an effect of the specific hydrogen transfer between steroids]. After addition of estrone to rat liver slices, a quotient of estradiol/estrone of ca. 0.1 is reached within 1 - 2 min. By additional application of 17 beta-hydroxysteroids this quotient is changed in the direction of estradiol, although the applied concentrations of both steroids are far below the concentration of the cytoplasmic redox couple NADH/NAD. Of all the steroids tested, testosterone had the strongest influence on the quotient, especially in the liver of female rats. This influence is smaller in the livers of male rats and infantile animals. The changing of the E2/E1 quotient by testosterone can be inhibited by the antiandrogen cyproteron acetate. Steroids with hydroxy groups at C-3 or C-20 or high concentrations of non-steroids, which can be oxidized by NAD, change the E2/E1 quotient only minimally. The experiments demonstrate that in liver, the redox couple estradiol/estrone is not in equilibrium with the main redox couple of the cytoplasmic NADH/NAD. Only on account of this fact it is possible that relatively low concentrations of testosterone change the E2/E1 quotient via the C-17 leads to C-17 hydrogen transfer between steroids. Biological consequences are discussed."} {"id": "PMID:168144", "title": "Adopting new models for continuity of care: the ward as mini-mental-health-center.", "content": "Several years ago the staff of a traditional psychiatric ward in a Veterans Administration hospital began trying to provide continual care for their former inpatients after they left the hospital. Nursing assistants conducted basic-skills groups and other groups in board-and-care homes; staff members made themselves available to former inpatients and theri families, roommates, or board-and-care sponsors through a 24-hour telephone service and home visits; and a day-care program and follow-up groups for the ward's outpatients were set up. Later the staff establiched additional day-care and follow-up programs in a downtown satellite unit. In a recent three month period, patients made a total of 4488 visits to the satellite and hospital programs. The preceding paper discusses some of the theoretical considerations on which this program and other alternatives to traditional care are based.", "contents": "Adopting new models for continuity of care: the ward as mini-mental-health-center. Several years ago the staff of a traditional psychiatric ward in a Veterans Administration hospital began trying to provide continual care for their former inpatients after they left the hospital. Nursing assistants conducted basic-skills groups and other groups in board-and-care homes; staff members made themselves available to former inpatients and theri families, roommates, or board-and-care sponsors through a 24-hour telephone service and home visits; and a day-care program and follow-up groups for the ward's outpatients were set up. Later the staff establiched additional day-care and follow-up programs in a downtown satellite unit. In a recent three month period, patients made a total of 4488 visits to the satellite and hospital programs. The preceding paper discusses some of the theoretical considerations on which this program and other alternatives to traditional care are based."} {"id": "PMID:168145", "title": "On the distribution of some genetic markers in libya.", "content": "On a sample of N equals 169 nonrelated blood donors from Libya several blood group, serum protein group and enzyme frequencies are within the range of those of other Caucasoid populations. However, the frequencies of cDe, Jk-a, Fy-c, Hp-1, Gc-1, aP-b and AK-1 show some greater differences and seem to indicate certain Negroid influence on the genetic composition of our Libyan sample. This assumption is conceivable considering the racial history of Libya.", "contents": "On the distribution of some genetic markers in libya. On a sample of N equals 169 nonrelated blood donors from Libya several blood group, serum protein group and enzyme frequencies are within the range of those of other Caucasoid populations. However, the frequencies of cDe, Jk-a, Fy-c, Hp-1, Gc-1, aP-b and AK-1 show some greater differences and seem to indicate certain Negroid influence on the genetic composition of our Libyan sample. This assumption is conceivable considering the racial history of Libya."} {"id": "PMID:168146", "title": "Lipoproteins in lecithin-cholesterol-acyltransferase(LCAT)-deficiency. II. Further studies on the abnormal high-density-lipoproteins.", "content": "The lipoproteins from two sibs with familial lecithin-cholesterol-acyltransferase(LCAT)-deficiency were further characterized. Comparatively lipoproteins from patients with secondary LCAT-deficiency were studied. Both groups of patients had particles of unusual size and shape in the alpha1-(HD-2)-lipoprotein subfraction. The abnormal HDL-2 particles were disk-like in appearance with a major axis of about 180 A and a minor axis of about 40 A and tended to aggregate into long coinlike stacks. The abnormal HDL-2 particles contained the normal protein constituents of HDL Apo A-I, Apo A-II and Apo C but in addition a major polypeptide with a M.W. of 39000 not seen in significant amounts in normal high-density-lipoproteins. This polypeptide was found identical in size, isoelectric focusing and immunochemically with an arginine-rich normal polypeptide constituent of very-low-density-lipoproteins designated apoprotein E. Presence of this protein marker in the HDL allowed the specific immunological detection of the abnormal HDL-2 (LP-E) in plasma. Further minor biochemical abnormalities were observed in the lipoproteins of the patients with familial LCAT-deficiency. However, the main protein constituents of their HDL, the Apo A, Apo C and Apo E polypeptides, were found to be identical electrophoretically and by analytical isoelectric focusing with their normal counterparts. The data suggest that the basic genetic defect in the hereditary disease leads to a deficient activity of the LCAT-enzyme and that all abnormalities in the lipoprotein spectrum are secondary.", "contents": "Lipoproteins in lecithin-cholesterol-acyltransferase(LCAT)-deficiency. II. Further studies on the abnormal high-density-lipoproteins. The lipoproteins from two sibs with familial lecithin-cholesterol-acyltransferase(LCAT)-deficiency were further characterized. Comparatively lipoproteins from patients with secondary LCAT-deficiency were studied. Both groups of patients had particles of unusual size and shape in the alpha1-(HD-2)-lipoprotein subfraction. The abnormal HDL-2 particles were disk-like in appearance with a major axis of about 180 A and a minor axis of about 40 A and tended to aggregate into long coinlike stacks. The abnormal HDL-2 particles contained the normal protein constituents of HDL Apo A-I, Apo A-II and Apo C but in addition a major polypeptide with a M.W. of 39000 not seen in significant amounts in normal high-density-lipoproteins. This polypeptide was found identical in size, isoelectric focusing and immunochemically with an arginine-rich normal polypeptide constituent of very-low-density-lipoproteins designated apoprotein E. Presence of this protein marker in the HDL allowed the specific immunological detection of the abnormal HDL-2 (LP-E) in plasma. Further minor biochemical abnormalities were observed in the lipoproteins of the patients with familial LCAT-deficiency. However, the main protein constituents of their HDL, the Apo A, Apo C and Apo E polypeptides, were found to be identical electrophoretically and by analytical isoelectric focusing with their normal counterparts. The data suggest that the basic genetic defect in the hereditary disease leads to a deficient activity of the LCAT-enzyme and that all abnormalities in the lipoprotein spectrum are secondary."} {"id": "PMID:168147", "title": "Enzyme polymorphisms and haemoglobin variants in Greeks.", "content": "Several enzyme polymorphisms and hemoglobin variants were typed in a sample of n = 219 non-related Greek blood-donors. The following gene frequencies were observed: pa = 0.201, pb = 0.701, pc = 0.098;PGDA = 0.985, PGDc = 0.015; AK1 = 0.942, AK2 = 0.058; HbA = 0.988, HbS = 0.012. No polymorphic variation was seen in LDH, s-MDH, PHI, or SOD. The population genetical aspects of these results are discussed.", "contents": "Enzyme polymorphisms and haemoglobin variants in Greeks. Several enzyme polymorphisms and hemoglobin variants were typed in a sample of n = 219 non-related Greek blood-donors. The following gene frequencies were observed: pa = 0.201, pb = 0.701, pc = 0.098;PGDA = 0.985, PGDc = 0.015; AK1 = 0.942, AK2 = 0.058; HbA = 0.988, HbS = 0.012. No polymorphic variation was seen in LDH, s-MDH, PHI, or SOD. The population genetical aspects of these results are discussed."} {"id": "PMID:168149", "title": "Hypersarcosinemia with craniostenosis-syndactylism syndrome.", "content": "Hypersarcosinemia with craniostenosis-syndactylism syndrome. After a sarcosine loading the sarcosine-glycine ratios seem to be a more reliable criterion to distinguish different genotypes than the sarcosine tolerance curves.", "contents": "Hypersarcosinemia with craniostenosis-syndactylism syndrome. Hypersarcosinemia with craniostenosis-syndactylism syndrome. After a sarcosine loading the sarcosine-glycine ratios seem to be a more reliable criterion to distinguish different genotypes than the sarcosine tolerance curves."} {"id": "PMID:168148", "title": "Heterokaryons in the analysis of genes and gene regulation.", "content": "Cytological and chemical analysis of heterokaryons, the immediate product of cell fusion, offer new possibilities for studying the factors responsible for genetic regulation in eukaryotic cells. In comparison with proliferating cell hybrids the heterokaryon state offers the important advantage that a heterokaryon contains two complete genomes since chromosome loss does not occur, but since segregation and recombination are absent, heterokaryons cannot be used for gene mapping in the same way as proliferating cell hybrids. However, if two cell types carrying different genetic defects are fused the analysis can be used for studies of gene complementation. The biological information obtained with heterokaryons has emphasized the role of the cytoplasm in the control of nuclear activity. When a G1 nucleus is brought into contact with the cytoplasm of an S phase cell the G1 nucleus is stimulated to synthesize DNA. If the nucleus is brought into a mitotic cell, the chromatin of the G1 nucleus is forced to condense into prematurely condensed chromosomes. Inactive nuclei such as the dormant chick erythrocyte nucleus will be stimulated to initiate RNA and DNA synthesis when brought into contact with an active cytoplasm by cell fusion. Specific nuclear proteins have been shown to be responsible for this process of reactivation. Other inactive nuclei such as the nuclei of macrophages and spermatozoa have likewise been shown to be reactivated by fusion with active cells. The degree of activation in all of these cases appears to be determined by the state of the active cell. Inactive nuclei are activated to the same level as the active nucleus but seldom beyond this level. If differentiated cells are fused with undifferentiated cells, usually the differentiated character is lost rapidly after fusion. This observation is in agreement with several studies on proliferating cell hybrids indicating some type of negative control of differentiated properties. In heterokaryons obtained by fusion of cells of a similar type of histotypic differentiation usually coexpression of the differentiated markers is observed.", "contents": "Heterokaryons in the analysis of genes and gene regulation. Cytological and chemical analysis of heterokaryons, the immediate product of cell fusion, offer new possibilities for studying the factors responsible for genetic regulation in eukaryotic cells. In comparison with proliferating cell hybrids the heterokaryon state offers the important advantage that a heterokaryon contains two complete genomes since chromosome loss does not occur, but since segregation and recombination are absent, heterokaryons cannot be used for gene mapping in the same way as proliferating cell hybrids. However, if two cell types carrying different genetic defects are fused the analysis can be used for studies of gene complementation. The biological information obtained with heterokaryons has emphasized the role of the cytoplasm in the control of nuclear activity. When a G1 nucleus is brought into contact with the cytoplasm of an S phase cell the G1 nucleus is stimulated to synthesize DNA. If the nucleus is brought into a mitotic cell, the chromatin of the G1 nucleus is forced to condense into prematurely condensed chromosomes. Inactive nuclei such as the dormant chick erythrocyte nucleus will be stimulated to initiate RNA and DNA synthesis when brought into contact with an active cytoplasm by cell fusion. Specific nuclear proteins have been shown to be responsible for this process of reactivation. Other inactive nuclei such as the nuclei of macrophages and spermatozoa have likewise been shown to be reactivated by fusion with active cells. The degree of activation in all of these cases appears to be determined by the state of the active cell. Inactive nuclei are activated to the same level as the active nucleus but seldom beyond this level. If differentiated cells are fused with undifferentiated cells, usually the differentiated character is lost rapidly after fusion. This observation is in agreement with several studies on proliferating cell hybrids indicating some type of negative control of differentiated properties. In heterokaryons obtained by fusion of cells of a similar type of histotypic differentiation usually coexpression of the differentiated markers is observed."} {"id": "PMID:168150", "title": "Red-cell uridine-5-monophosphate kinase (UMPK): formal genetics, linkage analysis and population genetics from southwestern Germany.", "content": "In a population sample from southwestern Germany the frequency of UMPK1 was estimated to be 0.949. The segregation of the children's phenotypes is in agreement with the formal model: 2 common alleles UMPK1 and UMPK2 at an autosomal locus. Data on linkage relations are referred.", "contents": "Red-cell uridine-5-monophosphate kinase (UMPK): formal genetics, linkage analysis and population genetics from southwestern Germany. In a population sample from southwestern Germany the frequency of UMPK1 was estimated to be 0.949. The segregation of the children's phenotypes is in agreement with the formal model: 2 common alleles UMPK1 and UMPK2 at an autosomal locus. Data on linkage relations are referred."} {"id": "PMID:168151", "title": "Unusual sensitivity of rabbit cells to a nonbinding diphtheria toxin fragment.", "content": "Normal and transformed rabbit kidney cells are killed by heat-dissociated diphtheria toxin fragments, whereas human (heLa), mouse (L929), and hamster (BHK and 333-8-9) cells are not affected.", "contents": "Unusual sensitivity of rabbit cells to a nonbinding diphtheria toxin fragment. Normal and transformed rabbit kidney cells are killed by heat-dissociated diphtheria toxin fragments, whereas human (heLa), mouse (L929), and hamster (BHK and 333-8-9) cells are not affected."} {"id": "PMID:168152", "title": "Immunological relationship between delta herpesvirus of patas monkeys and varicells-zoster virus of humans.", "content": "The Delta herpesvirus (DHV) which produced outbreaks of exanthematous disease in patas monkeys was shown to have a close immunological relationship to varicella-zoster (V-Z) virus of man. Immunization of rhesus monkeys with DHV or V-Z virus resulted in the development of neutralizing antibodies to both viruses and also in the production of complement-fixing antibodies to V-Z virus. Immunoglobulin M neutralizing antibody to V-Z virus was demonstrated in the serum of a rhesus monkey immunized with DHV, suggesting a primary antibody response rather than recall of antibody to a related virus. Convalescent-phase sera from human zoster cases had comparable levels of neutralizing antibody for both DHV and V-Z virus. Patas monkeys involved in an outbreak of DHV infection showed seroconversion to both DHV and V-Z virus by neutralization tests and to V-Z virus by complement fixation tests. The demonstration of the close antigneic relationship between DHV and V-Z virus suggests that DHV may be useful in an animal model system for studies on the latency and reactivation of V-Z virus.", "contents": "Immunological relationship between delta herpesvirus of patas monkeys and varicells-zoster virus of humans. The Delta herpesvirus (DHV) which produced outbreaks of exanthematous disease in patas monkeys was shown to have a close immunological relationship to varicella-zoster (V-Z) virus of man. Immunization of rhesus monkeys with DHV or V-Z virus resulted in the development of neutralizing antibodies to both viruses and also in the production of complement-fixing antibodies to V-Z virus. Immunoglobulin M neutralizing antibody to V-Z virus was demonstrated in the serum of a rhesus monkey immunized with DHV, suggesting a primary antibody response rather than recall of antibody to a related virus. Convalescent-phase sera from human zoster cases had comparable levels of neutralizing antibody for both DHV and V-Z virus. Patas monkeys involved in an outbreak of DHV infection showed seroconversion to both DHV and V-Z virus by neutralization tests and to V-Z virus by complement fixation tests. The demonstration of the close antigneic relationship between DHV and V-Z virus suggests that DHV may be useful in an animal model system for studies on the latency and reactivation of V-Z virus."} {"id": "PMID:168153", "title": "Effects of Clostridium perfringens enterotoxin on metabolic indexes of everted rat ileal sacs.", "content": "Everted sacs of rat ileum were incubated in Ringer phosphate solution while oxygen uptake, glucose uptake, and lactate production were determined. Sacs treated with Clostridium perfringens enterotoxin, in the form of crude cell-free extract and purified protein, consumed significantly less oxygen than untreated sacs. However, the toxin-treated sacs took up glucose and produced lactate at levels that were not significantly different than those observed in controls. We conclude that oxidative metabolism is inhibited by the action of the toxin, whereas conversion of glucose to lactate via glycolysis seems unaffected", "contents": "Effects of Clostridium perfringens enterotoxin on metabolic indexes of everted rat ileal sacs. Everted sacs of rat ileum were incubated in Ringer phosphate solution while oxygen uptake, glucose uptake, and lactate production were determined. Sacs treated with Clostridium perfringens enterotoxin, in the form of crude cell-free extract and purified protein, consumed significantly less oxygen than untreated sacs. However, the toxin-treated sacs took up glucose and produced lactate at levels that were not significantly different than those observed in controls. We conclude that oxidative metabolism is inhibited by the action of the toxin, whereas conversion of glucose to lactate via glycolysis seems unaffected"} {"id": "PMID:168154", "title": "Specific macrophage immunity to Sendai virus: macrophage aggregation in vitro with Sendai virus by cytophilic antibodies.", "content": "When a 24-h tube culture of rabbit alveolar macrophages was infected with Sendai virus, the rate of infected cells was found to be limited. Even at a multiplicity of infection (MOI) of 500 plaque-forming units per cell, an average of 63% cells was found to synthesize viral antigens stainable by direct immunofluorescence. When the macrophages obtained from rabbits hyperimmunized by an intravenous injection of Sendai virus were infected under the same in vitro conditions, the rate of antigen synthesis averaged a low as 23%. At the time of infection of alveolar macrophages from immunized rabbits (immune macrophages), cell aggregation at an MOI 50 and cell fusion at an MOI 500 were found 24 h after infection, and these reactions were never encountered after the infection of nonimmune macrophages. When the immune macrophages were either pretreated by trypsin or incubated in medium at pH 4.0, the infection no longer caused the aggregation. The supernatant fluid obtained after incubation at pH 4.0 contained neutralizing antibody to Sendai virus. Conversely, when nonimmune macrophages were incubated in the presence of rabbit anti-Sendai virus serum or purified immunoglobulin G, the same aggregation reaction occurred after virus infection. Ultraviolet light-killed Sendai virus could be used as the counterpart of alive virus in the same aggregation reaction. These results suggest that the aggregation reaction of the immune macrophages could be attributed to the presence of specific cytophilic antibodies on their surface.", "contents": "Specific macrophage immunity to Sendai virus: macrophage aggregation in vitro with Sendai virus by cytophilic antibodies. When a 24-h tube culture of rabbit alveolar macrophages was infected with Sendai virus, the rate of infected cells was found to be limited. Even at a multiplicity of infection (MOI) of 500 plaque-forming units per cell, an average of 63% cells was found to synthesize viral antigens stainable by direct immunofluorescence. When the macrophages obtained from rabbits hyperimmunized by an intravenous injection of Sendai virus were infected under the same in vitro conditions, the rate of antigen synthesis averaged a low as 23%. At the time of infection of alveolar macrophages from immunized rabbits (immune macrophages), cell aggregation at an MOI 50 and cell fusion at an MOI 500 were found 24 h after infection, and these reactions were never encountered after the infection of nonimmune macrophages. When the immune macrophages were either pretreated by trypsin or incubated in medium at pH 4.0, the infection no longer caused the aggregation. The supernatant fluid obtained after incubation at pH 4.0 contained neutralizing antibody to Sendai virus. Conversely, when nonimmune macrophages were incubated in the presence of rabbit anti-Sendai virus serum or purified immunoglobulin G, the same aggregation reaction occurred after virus infection. Ultraviolet light-killed Sendai virus could be used as the counterpart of alive virus in the same aggregation reaction. These results suggest that the aggregation reaction of the immune macrophages could be attributed to the presence of specific cytophilic antibodies on their surface."} {"id": "PMID:168155", "title": "Measurement of biological activities of purified and crude enterotoxin of Clostridium perfringens.", "content": "Enterotoxin of Clostridium perfringens was assayed and compared with toxicity in mice and erythemal activity in guinea pigs. Conversion factors were used to express these biological activities of crude enterotoxin in terms of weight of pure enterotoxin protein. One microgram of enterotoxin was equivalent to 3.41 erythema units and to 0.68 mouse median lethal dose.", "contents": "Measurement of biological activities of purified and crude enterotoxin of Clostridium perfringens. Enterotoxin of Clostridium perfringens was assayed and compared with toxicity in mice and erythemal activity in guinea pigs. Conversion factors were used to express these biological activities of crude enterotoxin in terms of weight of pure enterotoxin protein. One microgram of enterotoxin was equivalent to 3.41 erythema units and to 0.68 mouse median lethal dose."} {"id": "PMID:168157", "title": "Pharmacodynamic study of the capillaries of normal and allergic (atopic) subjects.", "content": "Using the capillary resistance test as a method to study the cutaneous microvessels, a number of capillary active agents were investigated by applying them percutaneously in hydrophylic ointment base to manifestly allergic and definitely non-allergic volunteers. While the catecholamines and heparin increased capillary resistance in both allergic and non-allergic groups, metacholine, serotonin, the somatotropic hormone and nitroglycerin either did not change or decreased capillary resistance in the normal group and invariably increased it in the members of the allergic group. The effects of catecholamines were, completely or partially, blocked in the normal group by pretreatment of the skin with dibenzyline or propranolol. In the members of the allergic group, blockade was often weak or absent indicating some derangement in the adrenergic receptors. The significance of the findings is discussed.", "contents": "Pharmacodynamic study of the capillaries of normal and allergic (atopic) subjects. Using the capillary resistance test as a method to study the cutaneous microvessels, a number of capillary active agents were investigated by applying them percutaneously in hydrophylic ointment base to manifestly allergic and definitely non-allergic volunteers. While the catecholamines and heparin increased capillary resistance in both allergic and non-allergic groups, metacholine, serotonin, the somatotropic hormone and nitroglycerin either did not change or decreased capillary resistance in the normal group and invariably increased it in the members of the allergic group. The effects of catecholamines were, completely or partially, blocked in the normal group by pretreatment of the skin with dibenzyline or propranolol. In the members of the allergic group, blockade was often weak or absent indicating some derangement in the adrenergic receptors. The significance of the findings is discussed."} {"id": "PMID:168158", "title": "Lymphoproliferative disease in a cotton-top marmoset after inoculation with infectious mononucleosis-derived Epstein-Barr virus.", "content": "Injection of concentrated EBV derived from cells of the Kaplan line of infectious mononucleosis (IM) origin resulted in malignant lymphoproliferation in one out of three cotton-top marmosets 6 weeks after inoculation. Two additional animals receiving the same isolate after incubation with an antibody-containing human serum did not develop tumors. Inoculation of concentrated virus derived from the P3HR-1 line of Burkitt origin did not lead to lymphoproliferations in five marmosets. Three of these received non-neutralized, and two received neutralized P3HR-1 virus. The tumor obtained with the Kaplan isolate revealed characteristics of a lymphosarcome. It contained EBV-specific DNA. In addition, EBV-synthesizing lymphoblastoid lines were established from a tumorous lymph-node, as well as from the spleen of the diseased marmoset. Virus recovered from these lines transformed lymphocytes derived from spleens of healthy marmosets. The tumor-bearing animal developed low levels of anti-VCA antibodies during the course of tumor growth. These data demonstrate the oncogenic potential of EBV directly derived from cells of IM origin.", "contents": "Lymphoproliferative disease in a cotton-top marmoset after inoculation with infectious mononucleosis-derived Epstein-Barr virus. Injection of concentrated EBV derived from cells of the Kaplan line of infectious mononucleosis (IM) origin resulted in malignant lymphoproliferation in one out of three cotton-top marmosets 6 weeks after inoculation. Two additional animals receiving the same isolate after incubation with an antibody-containing human serum did not develop tumors. Inoculation of concentrated virus derived from the P3HR-1 line of Burkitt origin did not lead to lymphoproliferations in five marmosets. Three of these received non-neutralized, and two received neutralized P3HR-1 virus. The tumor obtained with the Kaplan isolate revealed characteristics of a lymphosarcome. It contained EBV-specific DNA. In addition, EBV-synthesizing lymphoblastoid lines were established from a tumorous lymph-node, as well as from the spleen of the diseased marmoset. Virus recovered from these lines transformed lymphocytes derived from spleens of healthy marmosets. The tumor-bearing animal developed low levels of anti-VCA antibodies during the course of tumor growth. These data demonstrate the oncogenic potential of EBV directly derived from cells of IM origin."} {"id": "PMID:168159", "title": "Reactivity of serum from rous-sarcoma-bearing chickens with autochthonous and with allogeneic tumor cells: preferential autochthonous recognition.", "content": "Complement-medicated cytotoxicity and indirect immunofluorescence assays showed that sera from random-bred chickens bearing Rous sarcoma (RS) tumors are usually more reactive in vitro against RS cells of autochthonous than of allogeneic origin. Absorption of such sera with autochthonous, but not with allogeneic, RS cells abrogated the fluorescence staining capacity. Sera from tumor-bearing birds did not stain normal chicken embryo cells (CEC), but reacted with a higher proportion of CEC transformed by the RS virus than with cultured PS tumor cells. Tumor cells incubated at 37 degrees C with autochthonous serum and fluorescent horse anti-chicken immunoglobulin conjugate displayed cell surface fluorescence patching.", "contents": "Reactivity of serum from rous-sarcoma-bearing chickens with autochthonous and with allogeneic tumor cells: preferential autochthonous recognition. Complement-medicated cytotoxicity and indirect immunofluorescence assays showed that sera from random-bred chickens bearing Rous sarcoma (RS) tumors are usually more reactive in vitro against RS cells of autochthonous than of allogeneic origin. Absorption of such sera with autochthonous, but not with allogeneic, RS cells abrogated the fluorescence staining capacity. Sera from tumor-bearing birds did not stain normal chicken embryo cells (CEC), but reacted with a higher proportion of CEC transformed by the RS virus than with cultured PS tumor cells. Tumor cells incubated at 37 degrees C with autochthonous serum and fluorescent horse anti-chicken immunoglobulin conjugate displayed cell surface fluorescence patching."} {"id": "PMID:168160", "title": "Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite.", "content": "Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one-half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination.", "contents": "Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite. Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one-half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination."} {"id": "PMID:168161", "title": "Antibodies to Epstein-Barr virus-associated nuclear antigen and to other viral and non-viral antigens in Hodgkin's disease.", "content": "Antibody reactivity to Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was investigated by means of the anticomplement immunofluorescence technique on sera from patients with Hodgkin's disease (HD) and from appropriate controls. Antibody levels to other EBV-determined antigens, i.e. viral capsid (VCA) and early antigens (EA), and to measles and rubella viruses, to cytomegalovirus (CMV), and to toxoplasma gondii were also measured. The results of anti-EBV antibody titrations demonstrated that anti-VCA, anti-EA and anti-EBNA reactivity was significantly higher in HD patients than in healthy subjects. There was no significant difference between the distribution of high rubella and measles antibody titers in HD and control sera. The GMT and the incidence of high titer anti-CMV and toxoplasma antibodies were greater in HD patients than in controls. The analysis of the data, according to histological subtypes, showed that the condition of lymphocyte depletion was associated in HD patients with the highest anti-EBNA antibody levels and the lymphocyte predominance with the lowest. This pattern seemed to be peculiar for anti-EBV reactivity, since anti-CMV and anti-toxoplasma antibody levels in the lymphocyte-depleted group of patients did not significantly differ from those of controls. No correlation was found between anti-VCA and anti-EBNA in individual sera of HD patients. This observation suggests that different mechanisms are probably responsible in HD for the release of EBV-related antigen from infected cells.", "contents": "Antibodies to Epstein-Barr virus-associated nuclear antigen and to other viral and non-viral antigens in Hodgkin's disease. Antibody reactivity to Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was investigated by means of the anticomplement immunofluorescence technique on sera from patients with Hodgkin's disease (HD) and from appropriate controls. Antibody levels to other EBV-determined antigens, i.e. viral capsid (VCA) and early antigens (EA), and to measles and rubella viruses, to cytomegalovirus (CMV), and to toxoplasma gondii were also measured. The results of anti-EBV antibody titrations demonstrated that anti-VCA, anti-EA and anti-EBNA reactivity was significantly higher in HD patients than in healthy subjects. There was no significant difference between the distribution of high rubella and measles antibody titers in HD and control sera. The GMT and the incidence of high titer anti-CMV and toxoplasma antibodies were greater in HD patients than in controls. The analysis of the data, according to histological subtypes, showed that the condition of lymphocyte depletion was associated in HD patients with the highest anti-EBNA antibody levels and the lymphocyte predominance with the lowest. This pattern seemed to be peculiar for anti-EBV reactivity, since anti-CMV and anti-toxoplasma antibody levels in the lymphocyte-depleted group of patients did not significantly differ from those of controls. No correlation was found between anti-VCA and anti-EBNA in individual sera of HD patients. This observation suggests that different mechanisms are probably responsible in HD for the release of EBV-related antigen from infected cells."} {"id": "PMID:168162", "title": "Nuclear proteins of rat liver and of an aminoazo-dye-induced hepatoma.", "content": "Nuclear proteins of rat liver and rat ascites hepatoma were fractionated by extraction in solutions of different salt concentration and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The difference between the electrophorograms of the different fractions of nuclear proteins isolated from liver and from hepatoma was found in the bands which have the same electrophoretic mobility as the main proteins of informofers and are extracted from nuclei at salt concentrations which extract informofers. These changes in the electrophoretic patterns of proteins with the solubility and mobility of the proteins of informofers could be related to the defective processing of heterogeneous nuclear RNA in the hepatoma. In addition the identity of electrophorograms of nuclear proteins isolated from liver and from hepatoma and the identity of most bands in the electrophorograms of nuclear proteins which are soluble in 0.35 M NaCl and chromosomal proteins which are not soluble at this salt concentration support the notion that these nonhistone nuclear proteins which can be identified as the major bands in electrophorograms of chromosomal proteins are not the specific regulators of gene expression.", "contents": "Nuclear proteins of rat liver and of an aminoazo-dye-induced hepatoma. Nuclear proteins of rat liver and rat ascites hepatoma were fractionated by extraction in solutions of different salt concentration and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The difference between the electrophorograms of the different fractions of nuclear proteins isolated from liver and from hepatoma was found in the bands which have the same electrophoretic mobility as the main proteins of informofers and are extracted from nuclei at salt concentrations which extract informofers. These changes in the electrophoretic patterns of proteins with the solubility and mobility of the proteins of informofers could be related to the defective processing of heterogeneous nuclear RNA in the hepatoma. In addition the identity of electrophorograms of nuclear proteins isolated from liver and from hepatoma and the identity of most bands in the electrophorograms of nuclear proteins which are soluble in 0.35 M NaCl and chromosomal proteins which are not soluble at this salt concentration support the notion that these nonhistone nuclear proteins which can be identified as the major bands in electrophorograms of chromosomal proteins are not the specific regulators of gene expression."} {"id": "PMID:168168", "title": "[Virus propagation, virus replication and virus elimination in the human skin in zoster].", "content": "The purpose of this study was to investigate the spreading, the replication and the elimination of Varicella-Zoster-Virus (ZV) in human skin. Typical skin lesions of thoracic zoster in different stages of development and of exanthematic vesicles in ophthalmic zoster were examined under the electron microscope. We found that ZV may be detected in fully developed vesicular skin lesions only, whereas in immature lesions and in the surrounding non involved skin axonal alterations may be seen, with no ZV present. The replication of the virus in the skin takes place almost exclusively in the malpighian keratinocytes of the involved epidermis. Blister formation in zoster is basically a result of the acantholysis of the infected epidermal cells. Mature ZV are then extruded into the intercellar space and become phagocytised by mononuclear cells which infiltrate the epidermis and eliminate the virus in large phagolysosomes. Only few virions were found in the dermis extracellularly or in dermal macrophages. In some of these cells stages of ZV-replication were also seen. Other cell types (i.e. Langerhans cells) were rarely infected. The application of the periodic acid-silver methenamine technique (PASM) in zoster revealed that a glycoprotein-rich coat surrounds each mature virion, obviously originating from the plasma membrane of the infected keratinocytes. This coat may be reason for the ability of the ZV to adhere on the cell surface and to infect the cell.", "contents": "[Virus propagation, virus replication and virus elimination in the human skin in zoster]. The purpose of this study was to investigate the spreading, the replication and the elimination of Varicella-Zoster-Virus (ZV) in human skin. Typical skin lesions of thoracic zoster in different stages of development and of exanthematic vesicles in ophthalmic zoster were examined under the electron microscope. We found that ZV may be detected in fully developed vesicular skin lesions only, whereas in immature lesions and in the surrounding non involved skin axonal alterations may be seen, with no ZV present. The replication of the virus in the skin takes place almost exclusively in the malpighian keratinocytes of the involved epidermis. Blister formation in zoster is basically a result of the acantholysis of the infected epidermal cells. Mature ZV are then extruded into the intercellar space and become phagocytised by mononuclear cells which infiltrate the epidermis and eliminate the virus in large phagolysosomes. Only few virions were found in the dermis extracellularly or in dermal macrophages. In some of these cells stages of ZV-replication were also seen. Other cell types (i.e. Langerhans cells) were rarely infected. The application of the periodic acid-silver methenamine technique (PASM) in zoster revealed that a glycoprotein-rich coat surrounds each mature virion, obviously originating from the plasma membrane of the infected keratinocytes. This coat may be reason for the ability of the ZV to adhere on the cell surface and to infect the cell."} {"id": "PMID:168170", "title": "The management of benign renal tumors of infancy. Case report of a congenital mesoblastic nephroma (leiomyomatous hamartoma).", "content": "A case of a benign renal tumor found in an infant of 11/2 months is reported. Its clinical, radiological and operative findings were similar to those described previously as Wilms' tumors. Only pathological examination revealed its benignancy. In view of the occurrence of benign congenital mesoblastic nephroma which is evidently not rare in infancy, and because of the side effects of adjuvant cytotoxic and X-ray therapy, the authors feel that the immediate therapeutic approach to a solid intrarenal tumor in infancy should be surgical only. Further therapy should depend on pathological findings.", "contents": "The management of benign renal tumors of infancy. Case report of a congenital mesoblastic nephroma (leiomyomatous hamartoma). A case of a benign renal tumor found in an infant of 11/2 months is reported. Its clinical, radiological and operative findings were similar to those described previously as Wilms' tumors. Only pathological examination revealed its benignancy. In view of the occurrence of benign congenital mesoblastic nephroma which is evidently not rare in infancy, and because of the side effects of adjuvant cytotoxic and X-ray therapy, the authors feel that the immediate therapeutic approach to a solid intrarenal tumor in infancy should be surgical only. Further therapy should depend on pathological findings."} {"id": "PMID:168171", "title": "Prevalence of pseudorabies in sows in central Illinois.", "content": "Of 1,224 serums from slaughtered sows from central Illinois, 52 (4.25%) were found to be positive for pseudorabies neutralizing antibody.", "contents": "Prevalence of pseudorabies in sows in central Illinois. Of 1,224 serums from slaughtered sows from central Illinois, 52 (4.25%) were found to be positive for pseudorabies neutralizing antibody."} {"id": "PMID:168172", "title": "On the effect of N-methyl-bis (3-mesyloxypropyl) amine hydroxychloride on Bacillus subtilis cells.", "content": "N-Methyl-bis (3-mesyloxypropyl)amine hydrochloride is now in use as an antitumer drug. In view of its activity against some bacteria the present work was conducted to study its mode of action of Bacillus subtilis. The compound was found to induce irreversible damage to bacterial DNA whereas its effect on RNA was temporary and depending on maintenance of effective concentrations of the compound.", "contents": "On the effect of N-methyl-bis (3-mesyloxypropyl) amine hydroxychloride on Bacillus subtilis cells. N-Methyl-bis (3-mesyloxypropyl)amine hydrochloride is now in use as an antitumer drug. In view of its activity against some bacteria the present work was conducted to study its mode of action of Bacillus subtilis. The compound was found to induce irreversible damage to bacterial DNA whereas its effect on RNA was temporary and depending on maintenance of effective concentrations of the compound."} {"id": "PMID:168173", "title": "Streptovirudins, new antibiotics with antibacterial and antiviral activity. I. Culture taxonomy, fermentation and production of streptovirudin complex.", "content": "A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (Krainsky, 1914) Waksman et Henrici, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses.", "contents": "Streptovirudins, new antibiotics with antibacterial and antiviral activity. I. Culture taxonomy, fermentation and production of streptovirudin complex. A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (Krainsky, 1914) Waksman et Henrici, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses."} {"id": "PMID:168175", "title": "Changes in strength of lung inflation reflex during prolonged inflation.", "content": "Recovery from respiratory inhibition produced by the lung inflation reflex was studied in anesthetized dogs, paralyzed and ventilated with a respiratory pump. During constant ventilation the lungs were periodically inflated using positive end-expiratory pressure, while the respiratory motor output was monitored in the phrenic nerve. Inhibition of the phrenic discharge was followed by gradual recovery throughout 8-min inflation periods despite constant blood gases. Recording afferent potentials in a vagus nerve indicated that adaptation of pulmonary stretch receptors contributed to the initial recovery of the phrenic discharge, but this recovery continued after the receptor discharge had stabilized. The phrenic discharge also recovered after initial inhibition in two situations which avoided stretch receptor adaptation: a) when the stretch receptor discharge from the separate lungs was alternated in an overlapping manner by asynchronous pulmonary ventilation, and b) during continuous electrical stimulation of a vagus nerve. Phrenic activity was temporarily increased above its control value after periods of lung inflation, asynchronous ventilation and vagal stimulation. It is concluded that the lung inflation reflex gradually attenuates during prolonged stimulation due to both stretch receptor adaptation and changes within the central pathways.", "contents": "Changes in strength of lung inflation reflex during prolonged inflation. Recovery from respiratory inhibition produced by the lung inflation reflex was studied in anesthetized dogs, paralyzed and ventilated with a respiratory pump. During constant ventilation the lungs were periodically inflated using positive end-expiratory pressure, while the respiratory motor output was monitored in the phrenic nerve. Inhibition of the phrenic discharge was followed by gradual recovery throughout 8-min inflation periods despite constant blood gases. Recording afferent potentials in a vagus nerve indicated that adaptation of pulmonary stretch receptors contributed to the initial recovery of the phrenic discharge, but this recovery continued after the receptor discharge had stabilized. The phrenic discharge also recovered after initial inhibition in two situations which avoided stretch receptor adaptation: a) when the stretch receptor discharge from the separate lungs was alternated in an overlapping manner by asynchronous pulmonary ventilation, and b) during continuous electrical stimulation of a vagus nerve. Phrenic activity was temporarily increased above its control value after periods of lung inflation, asynchronous ventilation and vagal stimulation. It is concluded that the lung inflation reflex gradually attenuates during prolonged stimulation due to both stretch receptor adaptation and changes within the central pathways."} {"id": "PMID:168176", "title": "High-pressure liquid chromatographic method for the determination of patulin in apple butter.", "content": "Patulin is extracted from apple butter samples with ethyl acetate and the extract is cleaned up on a silica gel column, using benzene-ethyl acetate (75+25) as the eluant. High-pressure liquid chromatography, using a 25 cm ZorbaxSil column, isooctane-ethyl ether-acetic acid (750+250+0.5) as the mobile solvent, and a 254 nm ultraviolet detector, is used for the determinative step. Under these conditions, patulin is eluted before 5-hydroxymethylfurfural, a component of apple butter which interferes with other liquid chromatographic and thin layer chromatographic methods. Recoveries of patulin added at levels of 34.6, 138.4, and 276.8 mug/kg ranged from 89.0 to 112.1%.", "contents": "High-pressure liquid chromatographic method for the determination of patulin in apple butter. Patulin is extracted from apple butter samples with ethyl acetate and the extract is cleaned up on a silica gel column, using benzene-ethyl acetate (75+25) as the eluant. High-pressure liquid chromatography, using a 25 cm ZorbaxSil column, isooctane-ethyl ether-acetic acid (750+250+0.5) as the mobile solvent, and a 254 nm ultraviolet detector, is used for the determinative step. Under these conditions, patulin is eluted before 5-hydroxymethylfurfural, a component of apple butter which interferes with other liquid chromatographic and thin layer chromatographic methods. Recoveries of patulin added at levels of 34.6, 138.4, and 276.8 mug/kg ranged from 89.0 to 112.1%."} {"id": "PMID:168177", "title": "Fluorometric measurement of aflatoxin adsorbed on florisil in minicolumns.", "content": "Filter fluorometers have been adapted to measure the fluorescence intensity of aflatoxin absorbed on a Florisil layer in minicolumns. The relationship between concentration and intensity is near linear in the aflatoxin range from 10 to 100 ng. Although individual aflatoxin fractions cannot be resolved, since the measure is one of total intensity, fluorometric measurements advance the minicolumn screening procedure to a semiquantitative level. The detection of 1 ng aflatoxin B1 is well within the limits of a filter fluorometer with a photomultiplier detector. A precision, expressed as per cent coefficient of variation, ranging from 1.2 to 4.2%, was obtained for standard B1 columns.", "contents": "Fluorometric measurement of aflatoxin adsorbed on florisil in minicolumns. Filter fluorometers have been adapted to measure the fluorescence intensity of aflatoxin absorbed on a Florisil layer in minicolumns. The relationship between concentration and intensity is near linear in the aflatoxin range from 10 to 100 ng. Although individual aflatoxin fractions cannot be resolved, since the measure is one of total intensity, fluorometric measurements advance the minicolumn screening procedure to a semiquantitative level. The detection of 1 ng aflatoxin B1 is well within the limits of a filter fluorometer with a photomultiplier detector. A precision, expressed as per cent coefficient of variation, ranging from 1.2 to 4.2%, was obtained for standard B1 columns."} {"id": "PMID:168178", "title": "Cyclic 3', 5'-adenosine monophosphate phosphodiesterase mutants of Salmonella typhimurium.", "content": "Positive selection procedures for mutants of Salmonella typhimurium lacking cyclic 3', 5'7-adenosine monophosphate (cAMP) phosphodiesterase have been devised. The gene (cpd) coding for this enzyme has been located on the chromosome and shown to be 25% co-transducible with metC using phage P22. The mutants have been used to investigate the role of the enzyme in the control of genes whose expression is known to be dependent on cAMP. Significant alterations in the regulation of some but not others of these genes have been observed in these mutants. Mutants lacking the cAMP phosphodiesterase are more sensitive than their parents to a variety of antibiotics that appear to enter the cell through cAMP-dependent transport systems. They grow faster than the wild type on succinate-ammonia-salts, and glucose-proline-salts media and are inhibited by added cAMP on glucose, citrate, or glycerol-ammonia salts media whereas the wild type is unaffected. Neither the growth of Salmonella typhimurium on glycerol or citrate media nor the level of acid hexose phosphatase in the strain is affected by the loss of cAMP phosphodiesterase. In addition, the mutant strains are extremely sensitive to high levels of cAMP. Loss of the cAMP phosphodiesterase in strains unable to synthesize cAMP (adenyl cyclase negative) reduces by 10-fold the requirement for exogenous cAMP for expression of catabolite-sensitive phenotypes. These results suggest that through its control of cAMP levels in the cell the phosphodiesterase may be involved in the regulation of certain classes of catabolite-sensitive operaons and also in protecting the cell against high levels of cAMP.", "contents": "Cyclic 3', 5'-adenosine monophosphate phosphodiesterase mutants of Salmonella typhimurium. Positive selection procedures for mutants of Salmonella typhimurium lacking cyclic 3', 5'7-adenosine monophosphate (cAMP) phosphodiesterase have been devised. The gene (cpd) coding for this enzyme has been located on the chromosome and shown to be 25% co-transducible with metC using phage P22. The mutants have been used to investigate the role of the enzyme in the control of genes whose expression is known to be dependent on cAMP. Significant alterations in the regulation of some but not others of these genes have been observed in these mutants. Mutants lacking the cAMP phosphodiesterase are more sensitive than their parents to a variety of antibiotics that appear to enter the cell through cAMP-dependent transport systems. They grow faster than the wild type on succinate-ammonia-salts, and glucose-proline-salts media and are inhibited by added cAMP on glucose, citrate, or glycerol-ammonia salts media whereas the wild type is unaffected. Neither the growth of Salmonella typhimurium on glycerol or citrate media nor the level of acid hexose phosphatase in the strain is affected by the loss of cAMP phosphodiesterase. In addition, the mutant strains are extremely sensitive to high levels of cAMP. Loss of the cAMP phosphodiesterase in strains unable to synthesize cAMP (adenyl cyclase negative) reduces by 10-fold the requirement for exogenous cAMP for expression of catabolite-sensitive phenotypes. These results suggest that through its control of cAMP levels in the cell the phosphodiesterase may be involved in the regulation of certain classes of catabolite-sensitive operaons and also in protecting the cell against high levels of cAMP."} {"id": "PMID:168179", "title": "Inhibition of an early event in the cell division cycle of Escherichia coli by FL1060, an amidinopenicillanic acid.", "content": "Analysis of exponential and synchronous cultures of Escherichia coli B/r after the addition of FL1060 indicates a block point for division by this agent some 15 to 20 min before the end of the preceding cell division cycle, a time corresponding to the beginning of the C period of the cell division cycle. Morphological examination of FL1060-treated synchronous cultures of E. coli /r was consistent with inhibition by FL1060 of a very early event in the cell division cycle. This event appears to be essential for normal cell surface elongation in a rod configuration. Temporary treatment of synchronous cultures of E. coli B/r with FL1060 resulted in division delay, the extent of which was a function of the duration of exposure to FL1060. However, even after relatively long times of FL1060 treatment the delayed divisions were still synchronous. Although FL1060 had no direct effect on deoxyribonucleic acid (DNA) synthesis, the synchronous delayed division occuring after temporary treatment with FL1060 were accompanied by a delay in the attainment of resistance of cell division to inhibitors of DNA, ribonucleic acid, and protein synthesis. These results suggest aht an FL1060-sensitive event initiates at the beginning of the C period of the cell division cycle of E. coli and is responsible for normal cell elongation. This cell elongation pathway procedes independently of DNA synthesis, but there is an interaction between this pathway and termination of a round of DNA replication in which a normal rod configuration is necessary to allow a signal for cell division to be generated upon completion of DNA replication.", "contents": "Inhibition of an early event in the cell division cycle of Escherichia coli by FL1060, an amidinopenicillanic acid. Analysis of exponential and synchronous cultures of Escherichia coli B/r after the addition of FL1060 indicates a block point for division by this agent some 15 to 20 min before the end of the preceding cell division cycle, a time corresponding to the beginning of the C period of the cell division cycle. Morphological examination of FL1060-treated synchronous cultures of E. coli /r was consistent with inhibition by FL1060 of a very early event in the cell division cycle. This event appears to be essential for normal cell surface elongation in a rod configuration. Temporary treatment of synchronous cultures of E. coli B/r with FL1060 resulted in division delay, the extent of which was a function of the duration of exposure to FL1060. However, even after relatively long times of FL1060 treatment the delayed divisions were still synchronous. Although FL1060 had no direct effect on deoxyribonucleic acid (DNA) synthesis, the synchronous delayed division occuring after temporary treatment with FL1060 were accompanied by a delay in the attainment of resistance of cell division to inhibitors of DNA, ribonucleic acid, and protein synthesis. These results suggest aht an FL1060-sensitive event initiates at the beginning of the C period of the cell division cycle of E. coli and is responsible for normal cell elongation. This cell elongation pathway procedes independently of DNA synthesis, but there is an interaction between this pathway and termination of a round of DNA replication in which a normal rod configuration is necessary to allow a signal for cell division to be generated upon completion of DNA replication."} {"id": "PMID:168180", "title": "Assembly of the mitochondrial membrane system: isolation of nuclear and cytoplasmic mutants of Saccharomyces cerevisiae with specific defects in mitochondrial functions.", "content": "A selection procedure is described which permits a large number of Saccharomyces cerevisiae mutants to be screened for specific lesions in mitochondrial respiratory enzymes and the adenosine triphosphatase. The method has been used to isolate nuclear mutant strains with specific lesions in coenzyme QH2-cytochrome c reductase, cytochrome oxidase, and adenosine triphosphatase. In addition, two cytoplasmic mutants have been found whose primary defect is in cytochrome oxidase, and others have been found that show variable degrees of abnormalities in their mitochondrial translation products.", "contents": "Assembly of the mitochondrial membrane system: isolation of nuclear and cytoplasmic mutants of Saccharomyces cerevisiae with specific defects in mitochondrial functions. A selection procedure is described which permits a large number of Saccharomyces cerevisiae mutants to be screened for specific lesions in mitochondrial respiratory enzymes and the adenosine triphosphatase. The method has been used to isolate nuclear mutant strains with specific lesions in coenzyme QH2-cytochrome c reductase, cytochrome oxidase, and adenosine triphosphatase. In addition, two cytoplasmic mutants have been found whose primary defect is in cytochrome oxidase, and others have been found that show variable degrees of abnormalities in their mitochondrial translation products."} {"id": "PMID:168181", "title": "Physiology and metabolism of pathogenic Neisseria: partial characterization of the respiratory chain of Neisseria gonorrhoeae.", "content": "The cell membrane-associated respiratory electron transport chain of Neisseria gonorrhoeae was examined using electron paramagnetic spectroscopy (EPR) at liquid helium temperatures and optical spectroscopy at liquid nitrogen and room temperatures. EPR spectra of dithionite-reduced particles indicated the presence of centers N-1 and N-3 in the site I region of the respiratory chain, whereas reduction with succinate revealed the existence of center S-1 from the succinate cytochrome c reductase segment. Free radical(s) resembling that due to falvin semiquinone were observed with both reductants. Low temperature (77 K) optical difference spectra indicated the presence of cytochromes with alpha band maxima at 549, 557, and 562. Bands at 567, 535, and 417 nm, characteristic of the CO compound of cytochrome o, were also identified. Cytochromes a1 and a3 were not detected; however, a broad but weak absorbance with an alpha band maximun at 600 nm and a Soret shoulder at 440 nm was observed. Hence the respiratory chain of N. gonorrhoeae appears to contain several nonheme iron centers, cytochrome c, two b cytochromes, with cytochrome o which probably serves as the terminal oxidase.", "contents": "Physiology and metabolism of pathogenic Neisseria: partial characterization of the respiratory chain of Neisseria gonorrhoeae. The cell membrane-associated respiratory electron transport chain of Neisseria gonorrhoeae was examined using electron paramagnetic spectroscopy (EPR) at liquid helium temperatures and optical spectroscopy at liquid nitrogen and room temperatures. EPR spectra of dithionite-reduced particles indicated the presence of centers N-1 and N-3 in the site I region of the respiratory chain, whereas reduction with succinate revealed the existence of center S-1 from the succinate cytochrome c reductase segment. Free radical(s) resembling that due to falvin semiquinone were observed with both reductants. Low temperature (77 K) optical difference spectra indicated the presence of cytochromes with alpha band maxima at 549, 557, and 562. Bands at 567, 535, and 417 nm, characteristic of the CO compound of cytochrome o, were also identified. Cytochromes a1 and a3 were not detected; however, a broad but weak absorbance with an alpha band maximun at 600 nm and a Soret shoulder at 440 nm was observed. Hence the respiratory chain of N. gonorrhoeae appears to contain several nonheme iron centers, cytochrome c, two b cytochromes, with cytochrome o which probably serves as the terminal oxidase."} {"id": "PMID:168182", "title": "Effect of cyclic nucleotides on the cyanide-insensitive respiration of polymorphonuclear leucocytes.", "content": "The effects of N6,O2'-dibutyryladenosine 3',5'-monophosphate (Bu2-cyclic AMP) and N2,O2'-dibutyrylguanosine 3',5'-monophosphate (Bu2-cyclic GMP) on the cyanide-insensitive respiration of guinea pig peritoneal exudate polymorphonuclear leucocytes were studied. Bu2-cyclic AMP inhibited the respiration induced both by phagocytosis of E. coli and by the interaction with trypsin-digested rat liver microsomes. The addition of theophylline gave rise to an inhibitory pattern similar to that with Bu2-cyclic AMP against both the respirations induced. On the other hand, Bu2-cyclic GMP did not affect the respiration induced by phagocytosis whereas it inhibited the respiration induced by the addition of myristic acid was inhibited by Bu2-cyclic AMP, which was similar to that with E. coli. The respiration induced by methylene blue was inhibited neither by Bu2-cyclic AMP nor by Bu2-cyclic GMP. These observations suggest that the cyanide-insensitive respiration of polymorphonuclear leucocytes may be classified into at least three types from the inhibitory pattern of cyclic AMP and cyclic GMP.", "contents": "Effect of cyclic nucleotides on the cyanide-insensitive respiration of polymorphonuclear leucocytes. The effects of N6,O2'-dibutyryladenosine 3',5'-monophosphate (Bu2-cyclic AMP) and N2,O2'-dibutyrylguanosine 3',5'-monophosphate (Bu2-cyclic GMP) on the cyanide-insensitive respiration of guinea pig peritoneal exudate polymorphonuclear leucocytes were studied. Bu2-cyclic AMP inhibited the respiration induced both by phagocytosis of E. coli and by the interaction with trypsin-digested rat liver microsomes. The addition of theophylline gave rise to an inhibitory pattern similar to that with Bu2-cyclic AMP against both the respirations induced. On the other hand, Bu2-cyclic GMP did not affect the respiration induced by phagocytosis whereas it inhibited the respiration induced by the addition of myristic acid was inhibited by Bu2-cyclic AMP, which was similar to that with E. coli. The respiration induced by methylene blue was inhibited neither by Bu2-cyclic AMP nor by Bu2-cyclic GMP. These observations suggest that the cyanide-insensitive respiration of polymorphonuclear leucocytes may be classified into at least three types from the inhibitory pattern of cyclic AMP and cyclic GMP."} {"id": "PMID:168183", "title": "Glycosaminoglycans and glycoproteins isolated from rabbit femur.", "content": "1. Complex carbohydrate fractions were extracted successively with 40% aqueous EDTA (pH 7.4) and 6M urea (PH 7.8) FROM ACETONE-DRIED bone powder of rabbit femur. 2. The carbohydrate fraction extracted with EDTA (E=Fr) was separated into five fractions,D1approximatelyD5 by DEAE-Dephadex A-50 column chromatography. Chemical and infrared spectral analyses, and enzymatic digestion indicate that D2 contained lessacidic glycoprotein, D3 contained sialoglycoprotein, D4 contained a low sulfated proteokeratan sulfate-like substance, and d5 contained glycoprotein-bound chondroitin sulfate A plus protein-free chondroitin sulfate A. 3. Two fractions, HU-D1 and HU-D2, were isolated from the carbohydrate fraction extracted with urea (HU-Fr) by successive digestion with collagenase [EC 3.4.99.5] and pronase, followed by gel-filtration on Sephadex G-100 and then DEAE-Sephadex A-50 column chromatography. HU-D1 and HU-D2 contained a low sulfated keratan sulfate-like substance linked to peptide and glycopeptide-bound chondroitin sulfated keratan sulfate-like substance linked to peptide and glycopeptide-bound chondroitin sulfate A, respectively. 4. The present findings indicate that rabbit femur contains low sulfated proteokeratan sulfate-like substances with varying sulfate contents and glycoprotein-bound chondroitin sulfate A as the principal glycosaminoglycans. The macromolecules bound more tightly to the tissue contain much more sulfate than the corresponding loosely bound ones.", "contents": "Glycosaminoglycans and glycoproteins isolated from rabbit femur. 1. Complex carbohydrate fractions were extracted successively with 40% aqueous EDTA (pH 7.4) and 6M urea (PH 7.8) FROM ACETONE-DRIED bone powder of rabbit femur. 2. The carbohydrate fraction extracted with EDTA (E=Fr) was separated into five fractions,D1approximatelyD5 by DEAE-Dephadex A-50 column chromatography. Chemical and infrared spectral analyses, and enzymatic digestion indicate that D2 contained lessacidic glycoprotein, D3 contained sialoglycoprotein, D4 contained a low sulfated proteokeratan sulfate-like substance, and d5 contained glycoprotein-bound chondroitin sulfate A plus protein-free chondroitin sulfate A. 3. Two fractions, HU-D1 and HU-D2, were isolated from the carbohydrate fraction extracted with urea (HU-Fr) by successive digestion with collagenase [EC 3.4.99.5] and pronase, followed by gel-filtration on Sephadex G-100 and then DEAE-Sephadex A-50 column chromatography. HU-D1 and HU-D2 contained a low sulfated keratan sulfate-like substance linked to peptide and glycopeptide-bound chondroitin sulfated keratan sulfate-like substance linked to peptide and glycopeptide-bound chondroitin sulfate A, respectively. 4. The present findings indicate that rabbit femur contains low sulfated proteokeratan sulfate-like substances with varying sulfate contents and glycoprotein-bound chondroitin sulfate A as the principal glycosaminoglycans. The macromolecules bound more tightly to the tissue contain much more sulfate than the corresponding loosely bound ones."} {"id": "PMID:168184", "title": "The participation of cytochromes in the reduction of N20 to N2 by a denitryfying bacterium.", "content": "The oxidation of cytochromes during the reduction of N2O to N2 by a denitrifying bacterium was studied spectrophotometrically. The reduced b- and c-type cytochromes are partially oxidized when N2O is added to intact cells reduced with lactate under anaerobic conditions. The oxidation of cytochromes is inhibited non-competitively by azide, cyanide, 2,4-dinitrophenol and CuSO4, which inhibit the reduction of N2O to N2. In the presence of each inhibitor at a high concentration, at which the reduction of N2O to N2 is perfectly inhibited, cytochromes are not oxidized by N2O, while when an adequate, low concentration of inhibitor is added, b-type cytochrome is partially oxidized but c-type cytochrome is apparently not oxidized. In cell-free extracts, prepared by the sonic disruption of cells, that have entirely lost their activity in the reduction of N2O to N2, cytochromes are not oxidized by N2O. From the above results, it was concluded that b-type and c-type cytochromes should participate in the electron transport mechanism of the reduction of N2O to N2.", "contents": "The participation of cytochromes in the reduction of N20 to N2 by a denitryfying bacterium. The oxidation of cytochromes during the reduction of N2O to N2 by a denitrifying bacterium was studied spectrophotometrically. The reduced b- and c-type cytochromes are partially oxidized when N2O is added to intact cells reduced with lactate under anaerobic conditions. The oxidation of cytochromes is inhibited non-competitively by azide, cyanide, 2,4-dinitrophenol and CuSO4, which inhibit the reduction of N2O to N2. In the presence of each inhibitor at a high concentration, at which the reduction of N2O to N2 is perfectly inhibited, cytochromes are not oxidized by N2O, while when an adequate, low concentration of inhibitor is added, b-type cytochrome is partially oxidized but c-type cytochrome is apparently not oxidized. In cell-free extracts, prepared by the sonic disruption of cells, that have entirely lost their activity in the reduction of N2O to N2, cytochromes are not oxidized by N2O. From the above results, it was concluded that b-type and c-type cytochromes should participate in the electron transport mechanism of the reduction of N2O to N2."} {"id": "PMID:168185", "title": "Prereplicative enzymic changes in regenerating rat liver.", "content": "After partial hepatectomy in rats, the following changes in enzymic activities were observed in the remnant liver during the prereplicative period. In the initial period of the prereplicative process, soon after removal of part of the liver, ornithine decarboxylase [EC 4.1.1.17] and IMP dehydrogenase [EC 1.2.1.14] increase. Subsequently, for entry into the S period, thymidine kinase [EC 2.7.1.75] increases simultaneously with increase in the intracellular cyclic AMP level and decrease in its phosphodiesterase [EC 3.1.4.17].", "contents": "Prereplicative enzymic changes in regenerating rat liver. After partial hepatectomy in rats, the following changes in enzymic activities were observed in the remnant liver during the prereplicative period. In the initial period of the prereplicative process, soon after removal of part of the liver, ornithine decarboxylase [EC 4.1.1.17] and IMP dehydrogenase [EC 1.2.1.14] increase. Subsequently, for entry into the S period, thymidine kinase [EC 2.7.1.75] increases simultaneously with increase in the intracellular cyclic AMP level and decrease in its phosphodiesterase [EC 3.1.4.17]."} {"id": "PMID:168186", "title": "Postitional specificity of fatty acids in pyrophosphatidic acid from Cryptococcus neoformans.", "content": "Pyrophosphatidic acid isolated from Cryptococcus neoformans was degraded to phosphatidic acid in aqueous pyridine. The phosphatidic acid was hydrolyzed by phospholipase A (EC 3.1.1.4) of Crotalus adamanteus to lysophosphatidic acid and 2-positioned fatty acids. From the analyses of the fatty acid composition of pyrophosphatidic acid and its degraded products (phosphatidid acid, lysophosphatidic acid, and fatty acid), it was concluded that most of the saturated fatty acids of pyrophosphatidic acid were at the 1,1'-positions while the unsaturated fatty acids were largely confined to the 2,2'-positions. The positional specificity of the fatty acids in pyrophosphatidic acid coincided with that of ordinary glycerophosphatides.", "contents": "Postitional specificity of fatty acids in pyrophosphatidic acid from Cryptococcus neoformans. Pyrophosphatidic acid isolated from Cryptococcus neoformans was degraded to phosphatidic acid in aqueous pyridine. The phosphatidic acid was hydrolyzed by phospholipase A (EC 3.1.1.4) of Crotalus adamanteus to lysophosphatidic acid and 2-positioned fatty acids. From the analyses of the fatty acid composition of pyrophosphatidic acid and its degraded products (phosphatidid acid, lysophosphatidic acid, and fatty acid), it was concluded that most of the saturated fatty acids of pyrophosphatidic acid were at the 1,1'-positions while the unsaturated fatty acids were largely confined to the 2,2'-positions. The positional specificity of the fatty acids in pyrophosphatidic acid coincided with that of ordinary glycerophosphatides."} {"id": "PMID:168187", "title": "Inhibition of Charonia lampas ascorbate-2-sulfate sulfohydrolase activity by adenosine 5'-diphosphate and related compounds.", "content": "1) ADP was a potent inhibitor of the ascorbic-2-sulfate sulfohydrolase activity of Charonia lampas liver. The inhibition was competitive with respect to ascorbate 2-sulfate. The Ki value was 5.9 muM. ADP did not inhibit arylsulfatase (EC 3.1.6.1) of the same organism. 2) Other nucleoside 5'-diphosphates and GTP showed similar inhibition of ascorbate-2-sulfate sulfohydrolase activity. 3) The effects of different nucleosides, nucleotides, and sugar phosphates on ascorbate-2-sulfate sulfohydrolase activity were investigated. Phosphate derivatives other than 3',5'-cyclic AMP were more or less inhibitory.", "contents": "Inhibition of Charonia lampas ascorbate-2-sulfate sulfohydrolase activity by adenosine 5'-diphosphate and related compounds. 1) ADP was a potent inhibitor of the ascorbic-2-sulfate sulfohydrolase activity of Charonia lampas liver. The inhibition was competitive with respect to ascorbate 2-sulfate. The Ki value was 5.9 muM. ADP did not inhibit arylsulfatase (EC 3.1.6.1) of the same organism. 2) Other nucleoside 5'-diphosphates and GTP showed similar inhibition of ascorbate-2-sulfate sulfohydrolase activity. 3) The effects of different nucleosides, nucleotides, and sugar phosphates on ascorbate-2-sulfate sulfohydrolase activity were investigated. Phosphate derivatives other than 3',5'-cyclic AMP were more or less inhibitory."} {"id": "PMID:168188", "title": "Inactivation and reactivation of phosphoprotein phosphatase of rabbit skeletal muscle. Role of ATP and divalent metal ions.", "content": "The regulatory mechanism of a phosphoprotein phosphatase (EC 3.1.3.16), which is considered to catalyze the dephosphorylation reaction of several phosphoproteins (glycogen synthetase-D (EC 2.4.1.11), phospho-form of phosphorylase b kinase (EC 2.7.1.38), phosphohistone and phosphorylase a (EC 2.4.1.1)), was studied with partially purified preparations from rabbit skeletal muscle. Time- and temperature-dependent inactivation and reactivation of phosphohistone phosphatase, as well as phosphorylase phosphatase (EC 3.1.3.17), were observed on pre0incubation of the enzyme(s) with ATP, and subsequent incubation with divalent metal ions (Mg2+, Mn2+, or Co2+) without any change of molecular size. Manganese, however, instantly restored the activity of the ATP-inactivated enzyme, and increased the maximal velocity of the enzyme while decreasing its affinity to phosphorylase a. However, the metal ion inhibited the reactivated enzyme competively with respect to phosphorylase a. It is suggested that phosphoprotein phosphatase(s) is a metalloenzyme, and that ATP results in a conformational change of the enzyme protein in such a way that a metal ion can be easily released due to the chelating effect of ATP, or incorporated (in the presence of excess metal ions) into the enzyme protein.", "contents": "Inactivation and reactivation of phosphoprotein phosphatase of rabbit skeletal muscle. Role of ATP and divalent metal ions. The regulatory mechanism of a phosphoprotein phosphatase (EC 3.1.3.16), which is considered to catalyze the dephosphorylation reaction of several phosphoproteins (glycogen synthetase-D (EC 2.4.1.11), phospho-form of phosphorylase b kinase (EC 2.7.1.38), phosphohistone and phosphorylase a (EC 2.4.1.1)), was studied with partially purified preparations from rabbit skeletal muscle. Time- and temperature-dependent inactivation and reactivation of phosphohistone phosphatase, as well as phosphorylase phosphatase (EC 3.1.3.17), were observed on pre0incubation of the enzyme(s) with ATP, and subsequent incubation with divalent metal ions (Mg2+, Mn2+, or Co2+) without any change of molecular size. Manganese, however, instantly restored the activity of the ATP-inactivated enzyme, and increased the maximal velocity of the enzyme while decreasing its affinity to phosphorylase a. However, the metal ion inhibited the reactivated enzyme competively with respect to phosphorylase a. It is suggested that phosphoprotein phosphatase(s) is a metalloenzyme, and that ATP results in a conformational change of the enzyme protein in such a way that a metal ion can be easily released due to the chelating effect of ATP, or incorporated (in the presence of excess metal ions) into the enzyme protein."} {"id": "PMID:168189", "title": "A simple method for preparation of snake venom phosphodiesterase almost free from 5'-nucleotidase.", "content": "A simple method, involving NAD+-Sepharose chromatography, was developed for the preparation of snake venom phosphodiesterase (EC 3.1.4.1) almost free from 5'-Nucleotidase (EC 3.1.3.5). Using an NAD+-Sepharose 4B column, phosphodiesterase was eluted in the unadsorbed fraction, whereas 5'nucleotidase was strongly adsorbed. The latter enzyme was desorbed when 0.2 M sodium bicarbonate buffer containing 1mM beta-NADH was used as a solvent. The affinity column could be used at least four times without any decrease of potency, and the method was applicable for the preparation of phosphodiesterase from the venoms of rattlesnake (Crotalus adamanteus) and Japanese mamushi (Agkistrodan halys blomhoffi).", "contents": "A simple method for preparation of snake venom phosphodiesterase almost free from 5'-nucleotidase. A simple method, involving NAD+-Sepharose chromatography, was developed for the preparation of snake venom phosphodiesterase (EC 3.1.4.1) almost free from 5'-Nucleotidase (EC 3.1.3.5). Using an NAD+-Sepharose 4B column, phosphodiesterase was eluted in the unadsorbed fraction, whereas 5'nucleotidase was strongly adsorbed. The latter enzyme was desorbed when 0.2 M sodium bicarbonate buffer containing 1mM beta-NADH was used as a solvent. The affinity column could be used at least four times without any decrease of potency, and the method was applicable for the preparation of phosphodiesterase from the venoms of rattlesnake (Crotalus adamanteus) and Japanese mamushi (Agkistrodan halys blomhoffi)."} {"id": "PMID:168190", "title": "Formate dehydrogenase. Subunit and mechanism of inhibition by cyanide and azide.", "content": "Formate dehydrogenase (EC 1.2.1.2) prepared from peas (Pisum sativum) was a two-subunit enzyme. The enzyme accelerated the formation of an NAD+-cyanide compound having an adsorption band at 330 nm. The enzyme was able to bind one NAD+ molecule per each subunit but only 1 mole of NAD+-cyanide compound was formed per two subunits. The complex of NAD+, cyanide, and the enzyme was very stable and had no catalytic activity. Azide inhibited the formate dehydrogenase reaction in two different ways. By incubation of the enzyme with azide in the presence of NAD+, half of its catalytic activity was lost. The remaining activity was also inhibited by azide but this inhibition was removed competively by formate. Contrary to the case of cyanide the inhibition by azide could be removed by dialysis and no spectral species due to the addition compound of NAD+ and azide could be observed. The data from double recipricol plots of the initial velocity and the formate concentration led to a conclusion that formate dehydrogenase has two sites with about equal catalytic activity. The Km for formate was different for the two catalytic sites (1.67 and 6.25 mM) but the difference was not noticeable in the case of the Km for NAD+.", "contents": "Formate dehydrogenase. Subunit and mechanism of inhibition by cyanide and azide. Formate dehydrogenase (EC 1.2.1.2) prepared from peas (Pisum sativum) was a two-subunit enzyme. The enzyme accelerated the formation of an NAD+-cyanide compound having an adsorption band at 330 nm. The enzyme was able to bind one NAD+ molecule per each subunit but only 1 mole of NAD+-cyanide compound was formed per two subunits. The complex of NAD+, cyanide, and the enzyme was very stable and had no catalytic activity. Azide inhibited the formate dehydrogenase reaction in two different ways. By incubation of the enzyme with azide in the presence of NAD+, half of its catalytic activity was lost. The remaining activity was also inhibited by azide but this inhibition was removed competively by formate. Contrary to the case of cyanide the inhibition by azide could be removed by dialysis and no spectral species due to the addition compound of NAD+ and azide could be observed. The data from double recipricol plots of the initial velocity and the formate concentration led to a conclusion that formate dehydrogenase has two sites with about equal catalytic activity. The Km for formate was different for the two catalytic sites (1.67 and 6.25 mM) but the difference was not noticeable in the case of the Km for NAD+."} {"id": "PMID:168191", "title": "Incorporation of nucleotides into DNA by mammalian DNA polymerase in the presence of a single deoxynucleoside triphosphate.", "content": "Rat ascites hepatoma cell DNA polymerases (EC 2.7.7.7), especially low molecular weight polymerase, could incorporate a significant amount of single nucleotide into acid-soluble products in the absence of the other three deoxynucleoside triphosphates when activated DNA was used as a template. This relaxed requirement for deoxynucleotides was not observed when poly[d(A-T).d(T-A)] was used as a template. Nearest-neighbour base analyses of the products formed in the presence of a single deoxynuclesode triphosphate revealed that the reaction is not of a terminal transferase-type but a very limited repair synthesis in which one or a few triphosphates are incorporated at numerous 3'-hydroxyl ends.", "contents": "Incorporation of nucleotides into DNA by mammalian DNA polymerase in the presence of a single deoxynucleoside triphosphate. Rat ascites hepatoma cell DNA polymerases (EC 2.7.7.7), especially low molecular weight polymerase, could incorporate a significant amount of single nucleotide into acid-soluble products in the absence of the other three deoxynucleoside triphosphates when activated DNA was used as a template. This relaxed requirement for deoxynucleotides was not observed when poly[d(A-T).d(T-A)] was used as a template. Nearest-neighbour base analyses of the products formed in the presence of a single deoxynuclesode triphosphate revealed that the reaction is not of a terminal transferase-type but a very limited repair synthesis in which one or a few triphosphates are incorporated at numerous 3'-hydroxyl ends."} {"id": "PMID:168192", "title": "Isolation and characterization of an alpha-amanitin-resistant rat myoblast mutant cell line possessing alpha-amanitin-resistant RNA polymerase II.", "content": "Cultures of the rat skeletal muscle myoblast cell line, L6, were treated with the mutagen ethylmethanesulfonate and grown in the presence of alpha-amanitin, an inhibitor of RNA polymerase II in vitro. One clonal cell line, Ama102, resistant tc the cytotoxic action of 2 mu-g/ml of alpha-amanitin was isolated and extensively characterized. Ama102 cells were about 30-fold more resistant to alpha-amanitin than their Ama+ parent cells based on a comparison of the concentration of alpha-amanitin required to reduce their plating efficiencies to similar extents. The RNA polymerase activities from Ama+ and Ama102 cells were solubilized and separated by DEAE-Sephadex chromatography. Whereas all of the Ama+ RNA polymerase II activity was inhibited by 0.1 mu-g/ml of alpha-amanitin, about 30% of the activity in the Ama102 RNA polymerase II peak was resistant to this concentration of alpha-amanitin and was inhibited only by much higher concentrations (25 mu-g/ml) of alpha-amanitin. This alpha-amanitin-resistant activity in Ama102 cells was identified as a bona fide RNA polymerase II by its chromatographic behavior on DEAE-Sephadex, salt optimum, preference for denatured DNA as template, insensitivity to inhibition by potassium phosphate, thermal inactivation kinetics, and inactivation by anti-RNA polymerase II antiserum. Both RNA polymerase IIa and IIb from Ama102 cells exhibited the partial alpha-amanitin resistance, as did this activity when purified further on phosphocellusose. Unlike the parental Ama+ cells, Ama102 cells neither fused at confluence nor showed an increase in the specific activity of creatine kinase. The altered sensitivity of the Ama102 RNA polymerase II to alpha-amanitin appears to account for the drug-resistant phenotype of these cells.", "contents": "Isolation and characterization of an alpha-amanitin-resistant rat myoblast mutant cell line possessing alpha-amanitin-resistant RNA polymerase II. Cultures of the rat skeletal muscle myoblast cell line, L6, were treated with the mutagen ethylmethanesulfonate and grown in the presence of alpha-amanitin, an inhibitor of RNA polymerase II in vitro. One clonal cell line, Ama102, resistant tc the cytotoxic action of 2 mu-g/ml of alpha-amanitin was isolated and extensively characterized. Ama102 cells were about 30-fold more resistant to alpha-amanitin than their Ama+ parent cells based on a comparison of the concentration of alpha-amanitin required to reduce their plating efficiencies to similar extents. The RNA polymerase activities from Ama+ and Ama102 cells were solubilized and separated by DEAE-Sephadex chromatography. Whereas all of the Ama+ RNA polymerase II activity was inhibited by 0.1 mu-g/ml of alpha-amanitin, about 30% of the activity in the Ama102 RNA polymerase II peak was resistant to this concentration of alpha-amanitin and was inhibited only by much higher concentrations (25 mu-g/ml) of alpha-amanitin. This alpha-amanitin-resistant activity in Ama102 cells was identified as a bona fide RNA polymerase II by its chromatographic behavior on DEAE-Sephadex, salt optimum, preference for denatured DNA as template, insensitivity to inhibition by potassium phosphate, thermal inactivation kinetics, and inactivation by anti-RNA polymerase II antiserum. Both RNA polymerase IIa and IIb from Ama102 cells exhibited the partial alpha-amanitin resistance, as did this activity when purified further on phosphocellusose. Unlike the parental Ama+ cells, Ama102 cells neither fused at confluence nor showed an increase in the specific activity of creatine kinase. The altered sensitivity of the Ama102 RNA polymerase II to alpha-amanitin appears to account for the drug-resistant phenotype of these cells."} {"id": "PMID:168193", "title": "Regulation of adenosine 3:5-monophosphate-dependent protein kinase.", "content": "The effects of epinephrine, glucagon, insulin and 1-methyl-3-isobutylxanthine on adenosine 3:5-monophosphate (cAMP)-dependent protein kinase activity were investigated in the perfused rat heart. The conditions for homogenization of heart tissue and assay of protein kinase are described. The activation state of the enzyme is expressed as the ratio of the rate of phosphorylation of histone in the absence to that in the presence of 2 mu-M cAMP. This activity ratio is stable in crude homogenates over 15 min of incubation; it is not affected by up to 30-fold dilution of the tissue volume. The ratio is elevated to a variable degree in hearts taken immediately from the animal but falls to a stable, basal level of 0.15 to 0.20 after 15 min of perfusion in vitro. An optimal concentration of epinephrine (10 mu-M) in the perfusate elevates cAMP from 0.5 to 1.3 nmol per g of tissue and increases the protein kinase activity ratio from 0.20 to 0.65. When hearts are perfused with a steady, submaximal concentration of epinephrine (0.4 mu-M), the level of cAMP and the protein kinase activity ratio rise in parallel within 15 s and remain elevated for at least 10 min. When epinephrine is removed from the perfusion medium, the level of cAMP and enzyme activity ratio decline rapidly to basal levels. Both glucagon and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine also increase the cardiac cAMP levels and protein kinase activity ratio in a dose-dependent manner. Glucagon acts as rapidly as does epinephrine whereas 1-methyl-3-isobutylxanthine requires at least 30 s before any effect can be observed. Insulin by itself does not significantly affect the cyclic nucleotide level or enzyme activity. The hormone has not been observed to lower the cAMP level or protein kinase activity in the heart under any conditions tested. In concentrations of 10 microunits per ml or greater, it does, however, cause a slight rise in the tissue level of cAMP and the protein kinase activity when these have been elevated to intermediate levels by exposure to epinephrine. This effect could only be observed when hearts were treated with catecholamine and could not be detected with glucagon or 1-methyl-3-isobutylxanthine. In all cases tested, slight increases in the protein kinase activity ratio (from 0.2 to 0.3) were accompanied by much greater increases in the amount of phosphorylase in the a form (20% to 70%). It was observed that at perfusion times greater than 3 min, there was a significant reduction in phosphorylase activity even though both the cAMP level and protein kinase activity remained elevated. In these studies, changes in the protein kinase activity correlate well with the tissue cAMP levels under all conditions tested.", "contents": "Regulation of adenosine 3:5-monophosphate-dependent protein kinase. The effects of epinephrine, glucagon, insulin and 1-methyl-3-isobutylxanthine on adenosine 3:5-monophosphate (cAMP)-dependent protein kinase activity were investigated in the perfused rat heart. The conditions for homogenization of heart tissue and assay of protein kinase are described. The activation state of the enzyme is expressed as the ratio of the rate of phosphorylation of histone in the absence to that in the presence of 2 mu-M cAMP. This activity ratio is stable in crude homogenates over 15 min of incubation; it is not affected by up to 30-fold dilution of the tissue volume. The ratio is elevated to a variable degree in hearts taken immediately from the animal but falls to a stable, basal level of 0.15 to 0.20 after 15 min of perfusion in vitro. An optimal concentration of epinephrine (10 mu-M) in the perfusate elevates cAMP from 0.5 to 1.3 nmol per g of tissue and increases the protein kinase activity ratio from 0.20 to 0.65. When hearts are perfused with a steady, submaximal concentration of epinephrine (0.4 mu-M), the level of cAMP and the protein kinase activity ratio rise in parallel within 15 s and remain elevated for at least 10 min. When epinephrine is removed from the perfusion medium, the level of cAMP and enzyme activity ratio decline rapidly to basal levels. Both glucagon and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine also increase the cardiac cAMP levels and protein kinase activity ratio in a dose-dependent manner. Glucagon acts as rapidly as does epinephrine whereas 1-methyl-3-isobutylxanthine requires at least 30 s before any effect can be observed. Insulin by itself does not significantly affect the cyclic nucleotide level or enzyme activity. The hormone has not been observed to lower the cAMP level or protein kinase activity in the heart under any conditions tested. In concentrations of 10 microunits per ml or greater, it does, however, cause a slight rise in the tissue level of cAMP and the protein kinase activity when these have been elevated to intermediate levels by exposure to epinephrine. This effect could only be observed when hearts were treated with catecholamine and could not be detected with glucagon or 1-methyl-3-isobutylxanthine. In all cases tested, slight increases in the protein kinase activity ratio (from 0.2 to 0.3) were accompanied by much greater increases in the amount of phosphorylase in the a form (20% to 70%). It was observed that at perfusion times greater than 3 min, there was a significant reduction in phosphorylase activity even though both the cAMP level and protein kinase activity remained elevated. In these studies, changes in the protein kinase activity correlate well with the tissue cAMP levels under all conditions tested."} {"id": "PMID:168194", "title": "Studies on highly metabolically active acetylation and phosphorylation of histones.", "content": "The capacity to effectively label tumor cell hostones using very short pulses of [3-H]acetate and [32-P]phosphate (1 to 10 min) has been developed. Four histone fractions F3, F2a1, F2a2, and F2b are extensively acetylated in short time periods. About 70% of the acetate accumulated on the histone during a short pulse is removed with a half-life of similar to 3 min. The rest of the metabolically active acetate is removed with a half-life of 30 to 40 min. Histones F2a1, F2a2, and F1 are acetylated at the NH2 terminus and this modification is metabolically stable. In short pulses, histones are labeled with 32-P in the order F2a2 greater than F1 greater than F3 greater than F2a1 greater than F2b. All fractions have a fairly rapid turnover time (t1/2 similar 20 to 40 min) except F1 phosphate which turns over some 5 times more slowly.", "contents": "Studies on highly metabolically active acetylation and phosphorylation of histones. The capacity to effectively label tumor cell hostones using very short pulses of [3-H]acetate and [32-P]phosphate (1 to 10 min) has been developed. Four histone fractions F3, F2a1, F2a2, and F2b are extensively acetylated in short time periods. About 70% of the acetate accumulated on the histone during a short pulse is removed with a half-life of similar to 3 min. The rest of the metabolically active acetate is removed with a half-life of 30 to 40 min. Histones F2a1, F2a2, and F1 are acetylated at the NH2 terminus and this modification is metabolically stable. In short pulses, histones are labeled with 32-P in the order F2a2 greater than F1 greater than F3 greater than F2a1 greater than F2b. All fractions have a fairly rapid turnover time (t1/2 similar 20 to 40 min) except F1 phosphate which turns over some 5 times more slowly."} {"id": "PMID:168195", "title": "The anomeric form of D-fructose 1,6-bisphosphate used as substrate in the muscle and yeast aldolase reactions.", "content": "From a series of rapid quench kinetic experiments, it has been demonstrated that muscle D-fructose bisphosphate aldolase catalyzes the cleavage of beta-D-fructose 1,6-bisphosphate but not that of the alpha anomer, although the alpha anomer may be tightly bound. Yeast D-fructose bisphosphate aldolase appears to utilize both alpha and beta anomers of the substrate, with yeast apoaldolase catalyzing the interconversion of the alpha and beta forms.", "contents": "The anomeric form of D-fructose 1,6-bisphosphate used as substrate in the muscle and yeast aldolase reactions. From a series of rapid quench kinetic experiments, it has been demonstrated that muscle D-fructose bisphosphate aldolase catalyzes the cleavage of beta-D-fructose 1,6-bisphosphate but not that of the alpha anomer, although the alpha anomer may be tightly bound. Yeast D-fructose bisphosphate aldolase appears to utilize both alpha and beta anomers of the substrate, with yeast apoaldolase catalyzing the interconversion of the alpha and beta forms."} {"id": "PMID:168196", "title": "Activation of protein kinase in thyroid slices by thyroid-stimulating hormone.", "content": "Protein kinase activity in homogenates of control thyroid slices and those incubated with thyroid-stimulating hormone (TSH) and prostaglandin EI was assayed and correlated with changes in cyclic adenosine 3':5'-monophosphate (cAMP) concentrations and binding of [3H]cAMP. Both TSH and prostaglandin E1 (25 mug/ml) increased protein kinase activity and the activity ratio (expressed as activity - cAMP to activity plus cAMP). It is unlikely that such activation reflects effects of the increased cAMP liberated at the time of homogenization. Hormone-induced activation of protein kinase persisted even after the homogenate had been diluted so that its cAMP concentration would be insufficient to achieve maximal activation of the enzyme. In contrast to the previous results of J. D. Corbin, T. R. Soderling, and C. R. Park ((1973 J. Biol. Chem. 248, 1813) using adipose tissue, homogenization of thyroid tissue in 0.5 M NaCl and chromatography using Sephadex G-100 did not seem to stabilize dissociation of protein kinase into its receptor and catalytic subunits. However, increasing amounts of NaCl in the homogenizing buffer were associated with an increase in the cAMP independence of enzyme activity. Dilution of the homogenate did not change the protein kinase activity ratio whether the homogenizing buffer contained NcCl or not. Increasing concentrations of NaF inhibited protein kinase activity. Within 1 to 3 min of incubation of thyroid slices with TSH, protein kinase activity and the activity ratio were increased significantly. This correlated quite well with increased cAMP concentrations in the slices and inhibition of [3H]cAMP binding to the homogenates. Maximal activation of the enzyme was achieved by 10 min which corresponds to the time of maximal effect on cAMP concentrations. Activation of protein kinase was achieved by 0.125 milliunit/ml of TSH and maximal effects with 0.5 to 1.25 milliunits/ml. These amounts agree well with those required for other effects of TSH. Although larger amounts of TSH produced even greater increases in cAMP concentrations this was not always associated with augmented inhibition of [3H]cAMP binding. These results are compatible with the concept that the TSH-mediated increase in cAMP is associated with activation of protein kinase in the intact cell. They also suggest that not all of the intracellular cAMP is available for activation of protein kinase.", "contents": "Activation of protein kinase in thyroid slices by thyroid-stimulating hormone. Protein kinase activity in homogenates of control thyroid slices and those incubated with thyroid-stimulating hormone (TSH) and prostaglandin EI was assayed and correlated with changes in cyclic adenosine 3':5'-monophosphate (cAMP) concentrations and binding of [3H]cAMP. Both TSH and prostaglandin E1 (25 mug/ml) increased protein kinase activity and the activity ratio (expressed as activity - cAMP to activity plus cAMP). It is unlikely that such activation reflects effects of the increased cAMP liberated at the time of homogenization. Hormone-induced activation of protein kinase persisted even after the homogenate had been diluted so that its cAMP concentration would be insufficient to achieve maximal activation of the enzyme. In contrast to the previous results of J. D. Corbin, T. R. Soderling, and C. R. Park ((1973 J. Biol. Chem. 248, 1813) using adipose tissue, homogenization of thyroid tissue in 0.5 M NaCl and chromatography using Sephadex G-100 did not seem to stabilize dissociation of protein kinase into its receptor and catalytic subunits. However, increasing amounts of NaCl in the homogenizing buffer were associated with an increase in the cAMP independence of enzyme activity. Dilution of the homogenate did not change the protein kinase activity ratio whether the homogenizing buffer contained NcCl or not. Increasing concentrations of NaF inhibited protein kinase activity. Within 1 to 3 min of incubation of thyroid slices with TSH, protein kinase activity and the activity ratio were increased significantly. This correlated quite well with increased cAMP concentrations in the slices and inhibition of [3H]cAMP binding to the homogenates. Maximal activation of the enzyme was achieved by 10 min which corresponds to the time of maximal effect on cAMP concentrations. Activation of protein kinase was achieved by 0.125 milliunit/ml of TSH and maximal effects with 0.5 to 1.25 milliunits/ml. These amounts agree well with those required for other effects of TSH. Although larger amounts of TSH produced even greater increases in cAMP concentrations this was not always associated with augmented inhibition of [3H]cAMP binding. These results are compatible with the concept that the TSH-mediated increase in cAMP is associated with activation of protein kinase in the intact cell. They also suggest that not all of the intracellular cAMP is available for activation of protein kinase."} {"id": "PMID:168197", "title": "Purification and properties of a phosphohydrolase from Enterobacter aerogenes.", "content": "A phosphohydrolase from Enterobacter aerogenes which hydrolyzes phosphate mono- and diesters has been purified approximately 50-fold to apparent homoeneity and crystallized. The enzyme is produced when the bacteria utilize phosphate diesters as sole phosphorus source. From sedimentation equilibrium experiments the molecular weight of the native enzyme is 173,000; from sodium dodecyl sulfate polyacrylamide gel electrophoresis the subunit molecular weight is 29,000, indicating that the enzyme is hexameric. The hydrolytic activity of the enzyme using both mono- and diesters is maximal at pH 5; THE Km of the enzyme for bis-p-nitrophenyl phosphate is constant from pH 5 to 8.5 whereas that for p-nitrophenyl phosphate increases about 40-fold as the pH increases over the same range. The phosphodiesterase activity is not inhibited by chelating agents but is inhibited by several divalent metal ions. 31-P NMR spectroscopy was used to identify the hydrolysis products of glycoside cyclic phosphates. The enzyme-catalyzed hydrolysis of methyl beta-D-ribofuranoside cyclic 3:5-phosphate yields exclusively the 5-phosphate whereas that of adenosine 3:5-monophosphate yields a 4:1 mixture of 3- and 5- AMP.", "contents": "Purification and properties of a phosphohydrolase from Enterobacter aerogenes. A phosphohydrolase from Enterobacter aerogenes which hydrolyzes phosphate mono- and diesters has been purified approximately 50-fold to apparent homoeneity and crystallized. The enzyme is produced when the bacteria utilize phosphate diesters as sole phosphorus source. From sedimentation equilibrium experiments the molecular weight of the native enzyme is 173,000; from sodium dodecyl sulfate polyacrylamide gel electrophoresis the subunit molecular weight is 29,000, indicating that the enzyme is hexameric. The hydrolytic activity of the enzyme using both mono- and diesters is maximal at pH 5; THE Km of the enzyme for bis-p-nitrophenyl phosphate is constant from pH 5 to 8.5 whereas that for p-nitrophenyl phosphate increases about 40-fold as the pH increases over the same range. The phosphodiesterase activity is not inhibited by chelating agents but is inhibited by several divalent metal ions. 31-P NMR spectroscopy was used to identify the hydrolysis products of glycoside cyclic phosphates. The enzyme-catalyzed hydrolysis of methyl beta-D-ribofuranoside cyclic 3:5-phosphate yields exclusively the 5-phosphate whereas that of adenosine 3:5-monophosphate yields a 4:1 mixture of 3- and 5- AMP."} {"id": "PMID:168198", "title": "The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters.", "content": "The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters have been measured by flow microcalorimetry using a phosphohydrolase isolated from Enterobacter aerogenes as catalyst. The values so obtained (kilocalories per mol) (at 25 degrees) for sodium salts are: diethyl phosphate, minus 1.8 plus or minus 0.5; ethylene phosphate, minus 6.4 plus or minus 0.2; trimethylene phosphate, minus 3.0 plus or minus 0.2; tetramethylene phosphate, minus 2.2 plus or minus 0.1; methyl beta-D-ribofuranoside cyclic 3:5-phosphate, minus 11.1 plus or minus 0.2; methyl alpha-D-glucopyranoside cyclic 4:6-phosphate, minus 6.3 plus or minus 0.1; and cyclic adenosine 3:5-monophosphate (5-ester bond), minus 11.1 plus or minus 0.4 (10-minus 3 M Mg-2+). The enthalpy of hydrolysis of the 3-ester bond of cyclic adenosine 3:5-monophosphate (10-minus 3 M Mg-2+) has been revised to minus 11.1 plus or minus 0.2 kcal/mol from the value of minus 13.2 plus or minus 0.4 kcal/mol reported previously (greengard, p., rudolph, s.a., and sturtevant, j. m. (1969) j. biol. Chem. 244, 4798). All these values pertain to the hydrolysis of singly charged diesters to form singly charged monoesters. The data for the acyclic and monocyclic phosphodiesters are in qualitative agreement with their hydrolytic reactivities. The enthalpies measured for the hydrolysis of the glycoside cyclic phosphates cannot now be explained on the basis of their structures or reactivities; perhaps a contribution to the enthalpies by solvation or a previously unrecognized geometric strain effect may be responsible for the large exothermic enthalpies of these cyclic phosphate diesters. Changes in the heat capacity, increment Cp, for some of the hydrolytic reactions were also measured.", "contents": "The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters. The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters have been measured by flow microcalorimetry using a phosphohydrolase isolated from Enterobacter aerogenes as catalyst. The values so obtained (kilocalories per mol) (at 25 degrees) for sodium salts are: diethyl phosphate, minus 1.8 plus or minus 0.5; ethylene phosphate, minus 6.4 plus or minus 0.2; trimethylene phosphate, minus 3.0 plus or minus 0.2; tetramethylene phosphate, minus 2.2 plus or minus 0.1; methyl beta-D-ribofuranoside cyclic 3:5-phosphate, minus 11.1 plus or minus 0.2; methyl alpha-D-glucopyranoside cyclic 4:6-phosphate, minus 6.3 plus or minus 0.1; and cyclic adenosine 3:5-monophosphate (5-ester bond), minus 11.1 plus or minus 0.4 (10-minus 3 M Mg-2+). The enthalpy of hydrolysis of the 3-ester bond of cyclic adenosine 3:5-monophosphate (10-minus 3 M Mg-2+) has been revised to minus 11.1 plus or minus 0.2 kcal/mol from the value of minus 13.2 plus or minus 0.4 kcal/mol reported previously (greengard, p., rudolph, s.a., and sturtevant, j. m. (1969) j. biol. Chem. 244, 4798). All these values pertain to the hydrolysis of singly charged diesters to form singly charged monoesters. The data for the acyclic and monocyclic phosphodiesters are in qualitative agreement with their hydrolytic reactivities. The enthalpies measured for the hydrolysis of the glycoside cyclic phosphates cannot now be explained on the basis of their structures or reactivities; perhaps a contribution to the enthalpies by solvation or a previously unrecognized geometric strain effect may be responsible for the large exothermic enthalpies of these cyclic phosphate diesters. Changes in the heat capacity, increment Cp, for some of the hydrolytic reactions were also measured."} {"id": "PMID:168199", "title": "Pyridoxal phosphate. An anionic probe for protein amino groups exposed on the outer and inner surfaces of intact human red blood cells.", "content": "Pyridoxal phosphate is a potent probe for exploring the \"sidedness\" of proteins in the membrane of the intact red blood cell. It reacts with amino groups with a high degree of specificity, forming a Schiff's base that can be fixed as an irreversible bond upon reduction with NaBH4; its binding site can be identified by use of [3-H]pyridoxal phosphate or NaB3-H4; it can be used as a surface probe under conditions of minimal penetration, or it can be used as a probe for proteins on the inside of the membrane under conditions of substantial uptake. Pyridoxal phosphate uptake involves a rapid and a slow component. The former represents the binding to the outer surface of the membrane; it is not substantially affected by pH and temperature, but is reduced considerably by pretreatment of cells by 4,4-diisothiocyano-2,2-stilbenedisulfonic acid, a specific inhibitor of anion transport. The slow component represents penetration into the cell; it is blocked by high pH, low temperature, or pretreatment with the disulfonic stilbene. Pyridoxal phosphate itself is also an effective and specific inhibitor of the permeation of other anions. Under conditions of minimal uptake, the only labeled proteins are three glycoproteins and a protein of apparent molecular weight 95,000. Under conditions of substantial uptake into the cell, the other major protein bands seen by staining on acrylamide gels after electrophoresis are labeled. It is concluded that virtually all of the major membrane proteins interact with pyridoxal phosphate from one side of the membrane or the other. The differences in labeling under conditions of minimal or maximal uptake can, therefore, be attributed to the sidedness in the distribution of the membrane proteins rather than to differences in their reactivity.", "contents": "Pyridoxal phosphate. An anionic probe for protein amino groups exposed on the outer and inner surfaces of intact human red blood cells. Pyridoxal phosphate is a potent probe for exploring the \"sidedness\" of proteins in the membrane of the intact red blood cell. It reacts with amino groups with a high degree of specificity, forming a Schiff's base that can be fixed as an irreversible bond upon reduction with NaBH4; its binding site can be identified by use of [3-H]pyridoxal phosphate or NaB3-H4; it can be used as a surface probe under conditions of minimal penetration, or it can be used as a probe for proteins on the inside of the membrane under conditions of substantial uptake. Pyridoxal phosphate uptake involves a rapid and a slow component. The former represents the binding to the outer surface of the membrane; it is not substantially affected by pH and temperature, but is reduced considerably by pretreatment of cells by 4,4-diisothiocyano-2,2-stilbenedisulfonic acid, a specific inhibitor of anion transport. The slow component represents penetration into the cell; it is blocked by high pH, low temperature, or pretreatment with the disulfonic stilbene. Pyridoxal phosphate itself is also an effective and specific inhibitor of the permeation of other anions. Under conditions of minimal uptake, the only labeled proteins are three glycoproteins and a protein of apparent molecular weight 95,000. Under conditions of substantial uptake into the cell, the other major protein bands seen by staining on acrylamide gels after electrophoresis are labeled. It is concluded that virtually all of the major membrane proteins interact with pyridoxal phosphate from one side of the membrane or the other. The differences in labeling under conditions of minimal or maximal uptake can, therefore, be attributed to the sidedness in the distribution of the membrane proteins rather than to differences in their reactivity."} {"id": "PMID:168200", "title": "Protein kinase stimulation of a reconstituted cholesterol side chain cleavage enzyme system in the bovine corpus luteum.", "content": "A solubilized preparation of cytochrome P-450, obtained by treatment of mitochondria from bovine corpora lutea with phospholipase A, contained all of the necessary components for the cholesterol side chain cleavage activity. The solubilized cytochrome -450 preparation could be isolated essentially free of endogenous cholesterol side chain cleavage activity by various fractionation techniques. A cholesterol side chain cleavage enzyme system was reconstituted using the isolated cytochrome P-450 preparation and purified adrenodoxin and adrenodoxin reductase (components of the enzyme system purified from the adrenal cortex). Protein kinase was partially purified from the cytosol fraction of bovine corpora lutea. It was purified 43-fold and the activity was highly dependent on cyclic adenosine 3:5-monophosphate (cyclic AMP). When ATP and this partially purified cyclic AMP-dependent protein kinase were added to the reconstituted cholesterol side chain cleavage enzyme assay in which cytochrome P-450 was limiting, a stimulation (20 to 74%) of the conversion of cholesterol into pregnenolone was observed. This stimulation was statistically significant with p value less than 0.001. The stimulatory effect of the protein kinase appeared to be dependent on ATP and was not mimicked by bovine serum albumin, indicating that the effect was specific for protein kinase. Protein kinase caused a phosphorylation of the cytochrome P-450 preparation when large amounts of this preparation were used in the assay. It is concluded from these results that the direct activation of the cytochrome P-450 component of the cholesterol side chain cleavage by protein kinase may be one of the ways by which cyclic AMP mediates the effect of luteinizine.", "contents": "Protein kinase stimulation of a reconstituted cholesterol side chain cleavage enzyme system in the bovine corpus luteum. A solubilized preparation of cytochrome P-450, obtained by treatment of mitochondria from bovine corpora lutea with phospholipase A, contained all of the necessary components for the cholesterol side chain cleavage activity. The solubilized cytochrome -450 preparation could be isolated essentially free of endogenous cholesterol side chain cleavage activity by various fractionation techniques. A cholesterol side chain cleavage enzyme system was reconstituted using the isolated cytochrome P-450 preparation and purified adrenodoxin and adrenodoxin reductase (components of the enzyme system purified from the adrenal cortex). Protein kinase was partially purified from the cytosol fraction of bovine corpora lutea. It was purified 43-fold and the activity was highly dependent on cyclic adenosine 3:5-monophosphate (cyclic AMP). When ATP and this partially purified cyclic AMP-dependent protein kinase were added to the reconstituted cholesterol side chain cleavage enzyme assay in which cytochrome P-450 was limiting, a stimulation (20 to 74%) of the conversion of cholesterol into pregnenolone was observed. This stimulation was statistically significant with p value less than 0.001. The stimulatory effect of the protein kinase appeared to be dependent on ATP and was not mimicked by bovine serum albumin, indicating that the effect was specific for protein kinase. Protein kinase caused a phosphorylation of the cytochrome P-450 preparation when large amounts of this preparation were used in the assay. It is concluded from these results that the direct activation of the cytochrome P-450 component of the cholesterol side chain cleavage by protein kinase may be one of the ways by which cyclic AMP mediates the effect of luteinizine."} {"id": "PMID:168201", "title": "Synthesis and turnover of intracisternal A-particle structural protein in cultured neuroblastoma cells.", "content": "Synthesis and turnover of the main structural protein (P73) of intracisternal A-particles were studied in mouse neuroblastoma cells in tissue culture. Triton X-100:EDTA-insoluble pellets containing 95% of the A-particle antigen in the cells were prepared and analyzed by electrophoresis in Na dodecyl-SO4-minus polyacrylamide gels. A 73,000 molecular weight component was prominent in pellets from three lines of neuroblastoma which contain numerous A-particles and this component was identified as the A-particle structural protein P73. It was absent in pellets prepared from cells which do not contain A-particles. Incorporation of labeled amino acids into P73 represented approximately 1.2% of total cell incorporation and this proportion did not change when the cell growth changed from log phase to stationary phase. Label appeared P73 within 2 min after radioactive amino acids were added to the medium. Pulse-chase and inhibitor studies confirmed antigenic measurements in demonstrating that the pool of P73 not assembled into A-particles was small. Turnover studies showed that P73 gained and lost label more rapidly than the average cell protein. In one cell line which was thoroughly characterized, approximately 60% of the main A-particle protein was estimated to turn over in a 24-hour period. Although the cells released approximately 10% of the proteins synthesized into the culture fluid, A-particle protein did not appear to be released. Analysis of culture fluid failed to reveal A-particles, soluble A-particle proteins, or A-particle antigen. It appears, therefore, that the particles are relatively rapidly synthesized and degraded, and that turnover occurs entirely intracellularly.", "contents": "Synthesis and turnover of intracisternal A-particle structural protein in cultured neuroblastoma cells. Synthesis and turnover of the main structural protein (P73) of intracisternal A-particles were studied in mouse neuroblastoma cells in tissue culture. Triton X-100:EDTA-insoluble pellets containing 95% of the A-particle antigen in the cells were prepared and analyzed by electrophoresis in Na dodecyl-SO4-minus polyacrylamide gels. A 73,000 molecular weight component was prominent in pellets from three lines of neuroblastoma which contain numerous A-particles and this component was identified as the A-particle structural protein P73. It was absent in pellets prepared from cells which do not contain A-particles. Incorporation of labeled amino acids into P73 represented approximately 1.2% of total cell incorporation and this proportion did not change when the cell growth changed from log phase to stationary phase. Label appeared P73 within 2 min after radioactive amino acids were added to the medium. Pulse-chase and inhibitor studies confirmed antigenic measurements in demonstrating that the pool of P73 not assembled into A-particles was small. Turnover studies showed that P73 gained and lost label more rapidly than the average cell protein. In one cell line which was thoroughly characterized, approximately 60% of the main A-particle protein was estimated to turn over in a 24-hour period. Although the cells released approximately 10% of the proteins synthesized into the culture fluid, A-particle protein did not appear to be released. Analysis of culture fluid failed to reveal A-particles, soluble A-particle proteins, or A-particle antigen. It appears, therefore, that the particles are relatively rapidly synthesized and degraded, and that turnover occurs entirely intracellularly."} {"id": "PMID:168202", "title": "Quenching of protein fluorescence by transient intermediates in the liver alcohol dehydrogenase reaction.", "content": "The addition of saturating concentrations of NAD-+ and alcohol to liver alcohol dehydrogenase in a stopped flow fluorimeter results in a triphasic quenching of enzyme fluorescence. A rapid quenching occurs with a rate constant of 300 to 500 s-minus 1, followed by a slower reaction at 50 to 100 s-minus 1, and ultimately followed by a very slow reaction. The addition of NAD-+ to enzyme in the absence of substrate causes a rapid quenching of enzyme fluorescence at 300 to 500 s-minus 1, with the same amplitude as the rapid phase in the presence of substrate. These studies demonstrate that NAD-+ binding to liver alcohol dehydrogenase causes a conformational change at a rate compatible with the previously reported rate constant for proton release, indicating that proton release is probably coupled to the conformational change.", "contents": "Quenching of protein fluorescence by transient intermediates in the liver alcohol dehydrogenase reaction. The addition of saturating concentrations of NAD-+ and alcohol to liver alcohol dehydrogenase in a stopped flow fluorimeter results in a triphasic quenching of enzyme fluorescence. A rapid quenching occurs with a rate constant of 300 to 500 s-minus 1, followed by a slower reaction at 50 to 100 s-minus 1, and ultimately followed by a very slow reaction. The addition of NAD-+ to enzyme in the absence of substrate causes a rapid quenching of enzyme fluorescence at 300 to 500 s-minus 1, with the same amplitude as the rapid phase in the presence of substrate. These studies demonstrate that NAD-+ binding to liver alcohol dehydrogenase causes a conformational change at a rate compatible with the previously reported rate constant for proton release, indicating that proton release is probably coupled to the conformational change."} {"id": "PMID:168203", "title": "Purine and pyrimidine transport by cultured Novikoff cells. Specificities and mechanism of transport and relationship to phosphoribosylation.", "content": "Adenine, guanine, and hypoxanthine were rapidly incorporated into the acid-soluble nucleotide pool and nucleic acids by wild type Novikoff cells. Incorporation followed normal Michaelis-Menten kinetics, but the following evidence indicates that specific transport processes precede the phosphoribosyltransferase reactions and are the rate-limiting step in purine incorporation by whole cells. Cells of an azaguanine-resistant subline of Novikoff cells which lacked hypoxanthine-guanine phosphoribosyltransferase activity and failed to incorporate guanine or hypoxanthine into the nucleotide pool, exhibited uptake of guanine and hypoxanthine by a saturable process. Similarly, wild type cells which had been preincubated in a glucose-free basal medium containing KCN and iodoacetate transported guanine and hypoxanthine normally, although a conversion of these purines to nucleotides did not occur in these cells. The mutant and KCN-iodoacetate treated wild type cells also exhibited countertransport of guanine and hypoxanthine when preloaded with various purines, uracil, and pyrimidine nucleosides. The cells also possess a saturable transport system for uracil although they lack phosphoribosyltransferase activity for uracil. In the absence of phosphoribosylation, none of the substrates was accumulated against a concentration gradient. Thus transport is by facilitated diffusion (nonconcentrative transport). Furthermore, the apparent Km values for purine uptake by untreated wild type and azaguanine-resistant cells were higher and the apparent Vmax values were lower than those for the corresponding phosphoribosyltransferases...", "contents": "Purine and pyrimidine transport by cultured Novikoff cells. Specificities and mechanism of transport and relationship to phosphoribosylation. Adenine, guanine, and hypoxanthine were rapidly incorporated into the acid-soluble nucleotide pool and nucleic acids by wild type Novikoff cells. Incorporation followed normal Michaelis-Menten kinetics, but the following evidence indicates that specific transport processes precede the phosphoribosyltransferase reactions and are the rate-limiting step in purine incorporation by whole cells. Cells of an azaguanine-resistant subline of Novikoff cells which lacked hypoxanthine-guanine phosphoribosyltransferase activity and failed to incorporate guanine or hypoxanthine into the nucleotide pool, exhibited uptake of guanine and hypoxanthine by a saturable process. Similarly, wild type cells which had been preincubated in a glucose-free basal medium containing KCN and iodoacetate transported guanine and hypoxanthine normally, although a conversion of these purines to nucleotides did not occur in these cells. The mutant and KCN-iodoacetate treated wild type cells also exhibited countertransport of guanine and hypoxanthine when preloaded with various purines, uracil, and pyrimidine nucleosides. The cells also possess a saturable transport system for uracil although they lack phosphoribosyltransferase activity for uracil. In the absence of phosphoribosylation, none of the substrates was accumulated against a concentration gradient. Thus transport is by facilitated diffusion (nonconcentrative transport). Furthermore, the apparent Km values for purine uptake by untreated wild type and azaguanine-resistant cells were higher and the apparent Vmax values were lower than those for the corresponding phosphoribosyltransferases..."} {"id": "PMID:168204", "title": "Ontogeny of glucocorticoid receptors in rat liver.", "content": "Specific receptors for glucocorticoids are present in liver cytosols of rat fetuses at least as early as the 18th day of gestation. The concentration of the receptor begins to decline after the 20th day reaching undetectable levels shortly before and after parturition. The receptor can be detected again 1 to 2 hours after birth, and its levels increase markedly to higher than adult values between the 2nd and 5th day. The reason for the failure to detect specific hormone binding near parturition appears to be due to occupation of binding sites by endogenous steroids rather than the absence of the receptor. This is indicated by the demonstration of both cytoplasmic and nuclear receptor sites in liver slices of newborn rats incubated with labeled dexamethasone at 37 degrees. The cytoplasmic receptors of fetal and adult liver differ in their relative affinity for cortisol and corticosterone. The fetal receptors have a higher affinity for corticosterone than cortisol while the reverse is true for the adult receptors. These observations suggest either the existence of dissimilar receptors in fetal and adult liver or the presence of more than one type of receptor sites. It is therefore possible that subtle differences in the nature of hepatic receptors may be partly responsible for the maturation-dependent qualitative differences in tissue responsiveness to glucocorticoids.", "contents": "Ontogeny of glucocorticoid receptors in rat liver. Specific receptors for glucocorticoids are present in liver cytosols of rat fetuses at least as early as the 18th day of gestation. The concentration of the receptor begins to decline after the 20th day reaching undetectable levels shortly before and after parturition. The receptor can be detected again 1 to 2 hours after birth, and its levels increase markedly to higher than adult values between the 2nd and 5th day. The reason for the failure to detect specific hormone binding near parturition appears to be due to occupation of binding sites by endogenous steroids rather than the absence of the receptor. This is indicated by the demonstration of both cytoplasmic and nuclear receptor sites in liver slices of newborn rats incubated with labeled dexamethasone at 37 degrees. The cytoplasmic receptors of fetal and adult liver differ in their relative affinity for cortisol and corticosterone. The fetal receptors have a higher affinity for corticosterone than cortisol while the reverse is true for the adult receptors. These observations suggest either the existence of dissimilar receptors in fetal and adult liver or the presence of more than one type of receptor sites. It is therefore possible that subtle differences in the nature of hepatic receptors may be partly responsible for the maturation-dependent qualitative differences in tissue responsiveness to glucocorticoids."} {"id": "PMID:168205", "title": "Regulation of mitochondrial membrane assembly in Neurospora crassa. Transient expression of a respiratory mutant phenotype.", "content": "Cultures of mutant cni-1, a chromosomal mutant of Neurospora crassa, undergo a marked change in respiratory properties as the age of the culture increases. Early log phase cultures have a high level of respiration that is insensitive to inhibition by cyanide or antimycin A. Late log and stationary phase cultures have reduced rates of respiration. A high percentage of this respiration is inhibited by cyanide. Mitochondria from early log phase cni-1 have an excess of cytochrome c and little or no detectable cytochrome aa3. Mitochondria from late log and stationary phase cultures have levels of c-, b-, and a-type cytochromes that are not significantly different in concentration from those found in wild type cells. The cytochrome aa3 content and the cytochrome oxidase activity of cni-1 mitochondria increase 5- to 10-fold as the age of the culture increases. Mitochondria from early log phase cells of cni-1 synthesize only polypeptides of apparent molecular weights 7,000 to 10,000 and donot synthesize any of the mitochondrial components of cytochrome oxidase. Mitochondria from late log and stationary phase cells synthesize the normal complement of mitochondrial translation products including the mitochondrial components of cytochrome oxidase. The assembly of cytochrome oxidase is likely due to the availability of the mitochondrially synthesized components of the enzyme. The regulation of mitochondrial translation in the cni-1 mutant is independent of the nutrient content of the growth medium and is due to the accumulation or depletion of some component within the cell.", "contents": "Regulation of mitochondrial membrane assembly in Neurospora crassa. Transient expression of a respiratory mutant phenotype. Cultures of mutant cni-1, a chromosomal mutant of Neurospora crassa, undergo a marked change in respiratory properties as the age of the culture increases. Early log phase cultures have a high level of respiration that is insensitive to inhibition by cyanide or antimycin A. Late log and stationary phase cultures have reduced rates of respiration. A high percentage of this respiration is inhibited by cyanide. Mitochondria from early log phase cni-1 have an excess of cytochrome c and little or no detectable cytochrome aa3. Mitochondria from late log and stationary phase cultures have levels of c-, b-, and a-type cytochromes that are not significantly different in concentration from those found in wild type cells. The cytochrome aa3 content and the cytochrome oxidase activity of cni-1 mitochondria increase 5- to 10-fold as the age of the culture increases. Mitochondria from early log phase cells of cni-1 synthesize only polypeptides of apparent molecular weights 7,000 to 10,000 and donot synthesize any of the mitochondrial components of cytochrome oxidase. Mitochondria from late log and stationary phase cells synthesize the normal complement of mitochondrial translation products including the mitochondrial components of cytochrome oxidase. The assembly of cytochrome oxidase is likely due to the availability of the mitochondrially synthesized components of the enzyme. The regulation of mitochondrial translation in the cni-1 mutant is independent of the nutrient content of the growth medium and is due to the accumulation or depletion of some component within the cell."} {"id": "PMID:168206", "title": "Binding of glucocorticoid receptors to DNA.", "content": "DNA has been implicated as the nuclear acceptor for receptor-glucocorticoid complexes. The present study concerns the interaction of these complexes, isolated from cultured rat hepatoma cells, with purified DNA. This association is rapid, reaching a maximum within a few minutes at 0 degrees, whereas dissociation requires several hours. DNA binds neither free glucocorticoids nor those complexed with transcortin or cytosol proteins different from the receptor. Receptors which are not complexed by steroid have little or no affinity for DNA. \"Activation,\" necessary for the binding of receptor-steroid complexes to isolated nuclei, also enhances DNA binding. The capacity of DNA for binding receptor-steroid complexes is large; saturation was not observed at the complex concentrations studied, using either crude or partially purified receptor preparations. The association of complexes with DNA is inhibited by divalent cations, at increasing ionic strengths, and by mercurial reagents. Complexes bind equally well to bacterial, bacteriophage, or rat DNA; however, there was either no or substantially reduced binding by bacterial 23 S rRNA. The binding of complexes to native DNA is roughly 3-fold greater than to denatured DNA. These characteristics are consistent with the possibility that DNA is the nuclear acceptor for receptor-glucocorticoid complexes; however, the actual composition of the acceptor sites remains unknown.", "contents": "Binding of glucocorticoid receptors to DNA. DNA has been implicated as the nuclear acceptor for receptor-glucocorticoid complexes. The present study concerns the interaction of these complexes, isolated from cultured rat hepatoma cells, with purified DNA. This association is rapid, reaching a maximum within a few minutes at 0 degrees, whereas dissociation requires several hours. DNA binds neither free glucocorticoids nor those complexed with transcortin or cytosol proteins different from the receptor. Receptors which are not complexed by steroid have little or no affinity for DNA. \"Activation,\" necessary for the binding of receptor-steroid complexes to isolated nuclei, also enhances DNA binding. The capacity of DNA for binding receptor-steroid complexes is large; saturation was not observed at the complex concentrations studied, using either crude or partially purified receptor preparations. The association of complexes with DNA is inhibited by divalent cations, at increasing ionic strengths, and by mercurial reagents. Complexes bind equally well to bacterial, bacteriophage, or rat DNA; however, there was either no or substantially reduced binding by bacterial 23 S rRNA. The binding of complexes to native DNA is roughly 3-fold greater than to denatured DNA. These characteristics are consistent with the possibility that DNA is the nuclear acceptor for receptor-glucocorticoid complexes; however, the actual composition of the acceptor sites remains unknown."} {"id": "PMID:168207", "title": "Characterization of a human intestinal fucolipid with blood group Lea activity.", "content": "A fucolipid that carried human blood group Lea activity was isolated from human small intestine. It contianed fucose, galactose, N-acetyl glucosamine, glucose, and ceramide in a molar ratio of 1:2:1:1:1. After periodate oxidation only 1 molecule of galactose and the N-acetylglucosamine remained. Permethylation of the lipid gave derivatives of a terminal fucose and galactose residue together with 2,4,6-tri-O-methylgalactose and 2,3,6-tri-O-methylglucose. After removal of fucose the lipid could be converted to a ceramide trihexoside with beta-galactosidase, and this, in turn, to ceramide lactoside by the action of beta-N-acetylhexosaminidase. Both enzymes converted the defucosylated derivative to a ceramide monohexoside. The methylated and the methylated and reduced derivatives of the intact lipid gave ions in mass spectrometry for a terminal hexose and deoxyhexose, a terminal trisaccharide of hexose, deoxyhexose and N-acetylhexosamine, and terminal tetra-and pentasaccharides. Ceramide fragments characteristic of hydroxy fatty acids with 16, 22, 23, and 24 carbons were found together with those of phytospingosine as the major long chain base. On the basis of these results and the immunologic activity of the fucolipid, the following structure is proposed: betaGal (1 leads to 3)betaGlcNAc (1 leads to 3)betaGal (1 leads to 4)Glc-ceramide alphaFuc (1 leads to 4).", "contents": "Characterization of a human intestinal fucolipid with blood group Lea activity. A fucolipid that carried human blood group Lea activity was isolated from human small intestine. It contianed fucose, galactose, N-acetyl glucosamine, glucose, and ceramide in a molar ratio of 1:2:1:1:1. After periodate oxidation only 1 molecule of galactose and the N-acetylglucosamine remained. Permethylation of the lipid gave derivatives of a terminal fucose and galactose residue together with 2,4,6-tri-O-methylgalactose and 2,3,6-tri-O-methylglucose. After removal of fucose the lipid could be converted to a ceramide trihexoside with beta-galactosidase, and this, in turn, to ceramide lactoside by the action of beta-N-acetylhexosaminidase. Both enzymes converted the defucosylated derivative to a ceramide monohexoside. The methylated and the methylated and reduced derivatives of the intact lipid gave ions in mass spectrometry for a terminal hexose and deoxyhexose, a terminal trisaccharide of hexose, deoxyhexose and N-acetylhexosamine, and terminal tetra-and pentasaccharides. Ceramide fragments characteristic of hydroxy fatty acids with 16, 22, 23, and 24 carbons were found together with those of phytospingosine as the major long chain base. On the basis of these results and the immunologic activity of the fucolipid, the following structure is proposed: betaGal (1 leads to 3)betaGlcNAc (1 leads to 3)betaGal (1 leads to 4)Glc-ceramide alphaFuc (1 leads to 4)."} {"id": "PMID:168208", "title": "Insulin secretion. Interrelationships of glucose, cyclic adenosine 3:5-monophosphate, and calcium.", "content": "Glucose elevates both cyclic adenosine 3:5-monophosphate (cyclic AMP) and insulin secretion rapidly and in a parallel dose-dependent fashion in perifused rat islets. Theophylline stimulates cyclic AMP much more than glucose, yet secretion is much less. When the two agents are combined, cyclic AMP is similar to theophylline alone yet secretion is augmented synergistically. Glucose-induced cyclic AMP generation and insulin secretion are dependent on extracellular calcium. Theophylline-induced insulin secretion is also extracellular calcium-dependent; however, theophylline-induced cyclic AMP elevation is independent of extracellular calcium. Thus, extracellular calcium has multiple effects on insulin secretion, some of which appear unrelated to a terminal secretory process. When glucose is combined with theophylline at physiologic levels of extracellular calcium, both the first and second phases of secretion are prominent. At extracellular calcium levels of 0.05 mM, only the second phase is prominent whereas at 10 nM extracellular calcium (ethylene glycol bis(beta-aminoethyl ether)-N,-tetraacetic acid) only the first phase is prominent. A divalent cation ionophore (a23187, Eli Lilly), which transports calcium and magnesium ions across biological membranes, was used to elucidate further the role of calcium and magnesium. If the ionophore (10 muM) is perifused for 5 min at low extracellular calcium and magnesium, and physiologic calcium is then added, a sudden spike of insulin release occurs in the absence of cyclic AMP generation. Similar results were obtained with magnesium. When the ionophore is perifused for 30 min at low calcium and magnesium, insulin secretion again occurs in the absence of cyclic AMP generation. Electron microscopic examination of the B cells following perifusion with the ionophore shows no specific alterations. These observations suggest that: (a) glucose elevates cyclic AMP, but the latter acts primarily as a positive feed-forward modulator of glucose-induced insulin release; and (b) extracellular calcium has multiple effects on insulin secretion both upon, and independent of, the cyclic AMP system.", "contents": "Insulin secretion. Interrelationships of glucose, cyclic adenosine 3:5-monophosphate, and calcium. Glucose elevates both cyclic adenosine 3:5-monophosphate (cyclic AMP) and insulin secretion rapidly and in a parallel dose-dependent fashion in perifused rat islets. Theophylline stimulates cyclic AMP much more than glucose, yet secretion is much less. When the two agents are combined, cyclic AMP is similar to theophylline alone yet secretion is augmented synergistically. Glucose-induced cyclic AMP generation and insulin secretion are dependent on extracellular calcium. Theophylline-induced insulin secretion is also extracellular calcium-dependent; however, theophylline-induced cyclic AMP elevation is independent of extracellular calcium. Thus, extracellular calcium has multiple effects on insulin secretion, some of which appear unrelated to a terminal secretory process. When glucose is combined with theophylline at physiologic levels of extracellular calcium, both the first and second phases of secretion are prominent. At extracellular calcium levels of 0.05 mM, only the second phase is prominent whereas at 10 nM extracellular calcium (ethylene glycol bis(beta-aminoethyl ether)-N,-tetraacetic acid) only the first phase is prominent. A divalent cation ionophore (a23187, Eli Lilly), which transports calcium and magnesium ions across biological membranes, was used to elucidate further the role of calcium and magnesium. If the ionophore (10 muM) is perifused for 5 min at low extracellular calcium and magnesium, and physiologic calcium is then added, a sudden spike of insulin release occurs in the absence of cyclic AMP generation. Similar results were obtained with magnesium. When the ionophore is perifused for 30 min at low calcium and magnesium, insulin secretion again occurs in the absence of cyclic AMP generation. Electron microscopic examination of the B cells following perifusion with the ionophore shows no specific alterations. These observations suggest that: (a) glucose elevates cyclic AMP, but the latter acts primarily as a positive feed-forward modulator of glucose-induced insulin release; and (b) extracellular calcium has multiple effects on insulin secretion both upon, and independent of, the cyclic AMP system."} {"id": "PMID:168209", "title": "A specific cyclic guanosine 3':5'-monophosphate-binding protein in Caulobacter crescentus.", "content": "A binding protein specific for cyclic guanosine 3':5'-monophosphate (cyclic GMP) has been partially purified from extracts of the eubacterium Caulobacter crescentus and resolved from cyclic adenosine 3':5'-monophosphate (cyclic AMP)-binding activity. Binding of cyclic GMP is not affected by the addition of cyclic AMP or 5'-GMP, but is inhibited about 50 percent by a 50-fold molar excess of dibutyryl cyclic GMP or cyclic hypoxanthine 3':5'-monophosphate. The apparent dissociation constant for the cyclic GMP-binding protein complex is 1.1 X 10(-6) M.", "contents": "A specific cyclic guanosine 3':5'-monophosphate-binding protein in Caulobacter crescentus. A binding protein specific for cyclic guanosine 3':5'-monophosphate (cyclic GMP) has been partially purified from extracts of the eubacterium Caulobacter crescentus and resolved from cyclic adenosine 3':5'-monophosphate (cyclic AMP)-binding activity. Binding of cyclic GMP is not affected by the addition of cyclic AMP or 5'-GMP, but is inhibited about 50 percent by a 50-fold molar excess of dibutyryl cyclic GMP or cyclic hypoxanthine 3':5'-monophosphate. The apparent dissociation constant for the cyclic GMP-binding protein complex is 1.1 X 10(-6) M."} {"id": "PMID:168210", "title": "Action of cytochalasin D on cells of established lines. III. Zeiosis and movements at the cell surface.", "content": "The projection of knobby protuberances at the cell surface (zeiosis) is a general cellular response to cytochalasin D (CD), resulting from herniation of endoplasm through undefended places of the cortex during cell contractions and displacement of microfilaments induced by CD. Zeiosis is prevented by agents that interfere with the contractile response to CD, such as inhibitors of energy metabolism or cyclic AMP. The developed protrusions, which remain relatively stable in the presence of CD, contain chiefly mono- or subribosomes, and occasionally other organelles normally resident in endoplasm; compact microfilament felt occupies their bases and extends into their proximal stalks. Protein synthesis in the knobs is less than half of that in the polyribosome-containing endoplasm residual in the main body of the cell. Knobs first protrude singly near the margin of the contracting cells and rapidly cluster into small groups in the periphery even at lower temperature. The clusters then migrate centripetally and coalesce into a large aggregate near the apex of the immobilized and retracted cell: this movement is energy- and temperature-dependent. Aggregation is more prominent and stable in cell lines of epithelial derivation than in fibroblastic or other lines in which nuclear extrusion occurs more readily. The latter is regarded as a special manifestation of zeiosis. Macromarkers, such as latex spherules, migrate like the zeiotic knobs on the cell surfaces in the presence of CD. The aggregated knobs, although persistent for days in the presence of CD, are rapidly recessed after withdrawal of the agent as ruffling is resumed and the cells spread. These movements are discussed in terms of current concepts of mobility of the cell membrane.", "contents": "Action of cytochalasin D on cells of established lines. III. Zeiosis and movements at the cell surface. The projection of knobby protuberances at the cell surface (zeiosis) is a general cellular response to cytochalasin D (CD), resulting from herniation of endoplasm through undefended places of the cortex during cell contractions and displacement of microfilaments induced by CD. Zeiosis is prevented by agents that interfere with the contractile response to CD, such as inhibitors of energy metabolism or cyclic AMP. The developed protrusions, which remain relatively stable in the presence of CD, contain chiefly mono- or subribosomes, and occasionally other organelles normally resident in endoplasm; compact microfilament felt occupies their bases and extends into their proximal stalks. Protein synthesis in the knobs is less than half of that in the polyribosome-containing endoplasm residual in the main body of the cell. Knobs first protrude singly near the margin of the contracting cells and rapidly cluster into small groups in the periphery even at lower temperature. The clusters then migrate centripetally and coalesce into a large aggregate near the apex of the immobilized and retracted cell: this movement is energy- and temperature-dependent. Aggregation is more prominent and stable in cell lines of epithelial derivation than in fibroblastic or other lines in which nuclear extrusion occurs more readily. The latter is regarded as a special manifestation of zeiosis. Macromarkers, such as latex spherules, migrate like the zeiotic knobs on the cell surfaces in the presence of CD. The aggregated knobs, although persistent for days in the presence of CD, are rapidly recessed after withdrawal of the agent as ruffling is resumed and the cells spread. These movements are discussed in terms of current concepts of mobility of the cell membrane."} {"id": "PMID:168211", "title": "Retention of endocrine function by an insulin-secreting pancreatic islet cell tumour from Syrain hamster through serial transplantation in nude mice.", "content": "An insulin-secreting islet cell tumour of the Syrian hamster has been transplanted serially in the congenitally immune-deficient nude mouse, in order to test the potential usefulness of this mouse mutant as a graft carrier of heterologous tumours with stable differentiated phenotypes. The incidence of tumour growth was very high, and the hamster tumour retained its functional and histologic characteristics during consecutive passages in nude mice. These results show that nude mice may be useful carriers of differentiated tumours from non-inbred species including man, and for the isolation of cell lines from such tumours.", "contents": "Retention of endocrine function by an insulin-secreting pancreatic islet cell tumour from Syrain hamster through serial transplantation in nude mice. An insulin-secreting islet cell tumour of the Syrian hamster has been transplanted serially in the congenitally immune-deficient nude mouse, in order to test the potential usefulness of this mouse mutant as a graft carrier of heterologous tumours with stable differentiated phenotypes. The incidence of tumour growth was very high, and the hamster tumour retained its functional and histologic characteristics during consecutive passages in nude mice. These results show that nude mice may be useful carriers of differentiated tumours from non-inbred species including man, and for the isolation of cell lines from such tumours."} {"id": "PMID:168212", "title": "Haemoglobin synthesis in fused cells.", "content": "When primitive erythroid cells from 5-day-old chick embryos are exposed to inactivated Sendai virus they do not undergo haemolysis but fuse with other cells by the normal process of cytoplasmic coalescence. In this way cells actively engaged in the synthesis of haemoglobin may be fused with others that are not. In heterokaryons formed by the fusion of such erythroid cells with cells from established mouse or hamster lines, haemoglobin synthesis initially continues at a high level, but then declines and ceases altogether within a period of about 60 h. This decline affects the synthesis of both haem and globin and reflects the activity of specific regulatory mechanism, for under these conditions other chick proteins continue to be synthesized. The haemoglobin synthesized in the heterokaryons is entirely chick, and not mouse or hamster, haemoglobin.", "contents": "Haemoglobin synthesis in fused cells. When primitive erythroid cells from 5-day-old chick embryos are exposed to inactivated Sendai virus they do not undergo haemolysis but fuse with other cells by the normal process of cytoplasmic coalescence. In this way cells actively engaged in the synthesis of haemoglobin may be fused with others that are not. In heterokaryons formed by the fusion of such erythroid cells with cells from established mouse or hamster lines, haemoglobin synthesis initially continues at a high level, but then declines and ceases altogether within a period of about 60 h. This decline affects the synthesis of both haem and globin and reflects the activity of specific regulatory mechanism, for under these conditions other chick proteins continue to be synthesized. The haemoglobin synthesized in the heterokaryons is entirely chick, and not mouse or hamster, haemoglobin."} {"id": "PMID:168216", "title": "Quantitative thin-layer chromatography of pyrimethamine and related diaminopyrimidines in body fluids and tissues.", "content": "Several 2,4-diaminopyrimidines which inhibit the enzyme dihydrofolate reductase are quantitated following extraction and separation on silica gel thin-layer chromatographic plates. These compounds are candidates for the treatment of brain tumors and meningeal leukemia, because they have the ability to cross the blood-brain barrier. The ultraviolet absorption of the pyrimidine ring at 275 nm is utilized to quantitate these compounds on thin-layer chromatographic plates with a scanning instrument. This method offers the advantages of speed, specificity, versatility and sensitivity, and has proven to be satisfactory for the measurement of as little as 10 ng/ml of these compounds in biological fluids.", "contents": "Quantitative thin-layer chromatography of pyrimethamine and related diaminopyrimidines in body fluids and tissues. Several 2,4-diaminopyrimidines which inhibit the enzyme dihydrofolate reductase are quantitated following extraction and separation on silica gel thin-layer chromatographic plates. These compounds are candidates for the treatment of brain tumors and meningeal leukemia, because they have the ability to cross the blood-brain barrier. The ultraviolet absorption of the pyrimidine ring at 275 nm is utilized to quantitate these compounds on thin-layer chromatographic plates with a scanning instrument. This method offers the advantages of speed, specificity, versatility and sensitivity, and has proven to be satisfactory for the measurement of as little as 10 ng/ml of these compounds in biological fluids."} {"id": "PMID:168217", "title": "Thin-layer chromatography of sulphonamides on silica gel G and polyamide layers by means of a polar mobile phase.", "content": "A thin-layer chromatographic system based on polyamide or silica gel G layers and an aqueous mobile phase was used for the separation of a series of sulphonamides. A linear relationship between RM values on polyamide layers and the acetone concentration in the mobile phase allowed the calculation of extrapolated RM values. The influence of the nature of the stationary phase on the migration of compounds is discussed.", "contents": "Thin-layer chromatography of sulphonamides on silica gel G and polyamide layers by means of a polar mobile phase. A thin-layer chromatographic system based on polyamide or silica gel G layers and an aqueous mobile phase was used for the separation of a series of sulphonamides. A linear relationship between RM values on polyamide layers and the acetone concentration in the mobile phase allowed the calculation of extrapolated RM values. The influence of the nature of the stationary phase on the migration of compounds is discussed."} {"id": "PMID:168220", "title": "Improvements in the thin-layer chromatography of natural products. I. Thin-layer chromatography of the aflatoxins.", "content": "During the period which has elapsed since the aflatoxins were first isolated, one of the main problems has been the separation of the individual aflatoxins in pure form from aflatoxin-containing extracts. This separation has been best effected by thin-layer chromatography, and in this paper we describe how some of the difficulties may be overcome by using an appropriate combination of solvent system and silica gel preparation. For the examination of aflatoxin-containing extracts from the mycelia of Aspergillus flavus moulds, an initial freeze-drying step has been found to improve appreciably the quality of the chromatograms obtained.", "contents": "Improvements in the thin-layer chromatography of natural products. I. Thin-layer chromatography of the aflatoxins. During the period which has elapsed since the aflatoxins were first isolated, one of the main problems has been the separation of the individual aflatoxins in pure form from aflatoxin-containing extracts. This separation has been best effected by thin-layer chromatography, and in this paper we describe how some of the difficulties may be overcome by using an appropriate combination of solvent system and silica gel preparation. For the examination of aflatoxin-containing extracts from the mycelia of Aspergillus flavus moulds, an initial freeze-drying step has been found to improve appreciably the quality of the chromatograms obtained."} {"id": "PMID:168222", "title": "Separation of phenylthiohydantoin-amino acids by high-pressure liquid chromatography.", "content": "A method for the separation of all phenylthiohydantoin (PTH)-amino acids except PTH-arginine and PTH-histidine by high-pressure liquid chromatography on a silica column is described. Elution is performed with a concave solvent gradient from hexane-methanol-propanol (3980:9:11) to methanol-propanol (9:11). A complete run is achieved in 40 min with a pressure drop of 1000 p.s.i. over the 250 mm X 2.1 mm column. Eluted peaks of 2-5 nmole are easily detected by their ultraviolet absorption at 254 nm. This method is superior to existing gas-liquid and thin-layer chromatographic techniques since all PTH-amino acids except PTH-arginine and PTH-histidine may be both separated and quantitated in a single run of 40 min. The use of the technique in conjunction with an automated peptide sequence analyser is illustrated.", "contents": "Separation of phenylthiohydantoin-amino acids by high-pressure liquid chromatography. A method for the separation of all phenylthiohydantoin (PTH)-amino acids except PTH-arginine and PTH-histidine by high-pressure liquid chromatography on a silica column is described. Elution is performed with a concave solvent gradient from hexane-methanol-propanol (3980:9:11) to methanol-propanol (9:11). A complete run is achieved in 40 min with a pressure drop of 1000 p.s.i. over the 250 mm X 2.1 mm column. Eluted peaks of 2-5 nmole are easily detected by their ultraviolet absorption at 254 nm. This method is superior to existing gas-liquid and thin-layer chromatographic techniques since all PTH-amino acids except PTH-arginine and PTH-histidine may be both separated and quantitated in a single run of 40 min. The use of the technique in conjunction with an automated peptide sequence analyser is illustrated."} {"id": "PMID:168223", "title": "Gas chromatography of amino acids.", "content": "This review summarizes all papers that have appeared on the gas chromatography of amino acids (including the iodoamino acids) and their enantiomers in the period 1956-mid-1974. It has been found that the methods used for analysis of amino acids can be divided into three classes: (1) degradative procedures and techniques for converting the amino acid into another chemical compound; (2) procedures based on esterification of the carboxyl group and derivatization of the a-amino and other reactive groups in at least two steps; and (3) procedures based on a simultaneous derivatization of the carboxyl and a-amino groups in one reaction medium. For the treatment of the amino acid or its alkyl ester, three approaches can be distinguished for the two latter cases, i.e., acylation, alkylation (including silylation) and condensation. Of the procedures used for the resolution of optical antipodes, two methods are discussed, namely analysis of diastereoisomers on optically inactive stationary phases and separation of enantiomers on optically active stationary phases.", "contents": "Gas chromatography of amino acids. This review summarizes all papers that have appeared on the gas chromatography of amino acids (including the iodoamino acids) and their enantiomers in the period 1956-mid-1974. It has been found that the methods used for analysis of amino acids can be divided into three classes: (1) degradative procedures and techniques for converting the amino acid into another chemical compound; (2) procedures based on esterification of the carboxyl group and derivatization of the a-amino and other reactive groups in at least two steps; and (3) procedures based on a simultaneous derivatization of the carboxyl and a-amino groups in one reaction medium. For the treatment of the amino acid or its alkyl ester, three approaches can be distinguished for the two latter cases, i.e., acylation, alkylation (including silylation) and condensation. Of the procedures used for the resolution of optical antipodes, two methods are discussed, namely analysis of diastereoisomers on optically inactive stationary phases and separation of enantiomers on optically active stationary phases."} {"id": "PMID:168225", "title": "The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration.", "content": "The plasma cortisol response to hypoglycemia is widely used as a test of hypothalamic-pituitary-adrenal function. It was the aim of this study to determine whether this test gives a reliable indication of pituitary corticotropin (ACTH) release in patients recovering from adrenocortical suppression due to corticosteroid or ACTH therapy. The 16 patients who were studied (6 on more than one occasion) had received in excess of 5 mg predinisone or equivalent daily for over 12 months. The insulin tolerance tests were carried out 18 h after stopping steroid therapy. The tests were then repeated three to four days after adrenal function had been restored (as indicated by urinary oxogenic steroid excretion of greater than 35 mg/24 h) by zinc tetracosactrin administration. The ACTH response to hypoglycemia was significantly impaired in the steroid-treated group. However with the exception of one patient who had persistently elevated resting ACTH levels there was a significant correlation (P less than 0.01) between the maximum increments in plasma cortisol and ACTH during hypoglycemia. No significant difference in sensitivity to endogenous ACTH could be demonstrated between the steroid-treated group and 12 normal control subjects. Following ACTH administration the plasma ACTH and growth hormone responses to hypoglycemia were significantly reduced, but the response in plasma cortisol was not significantly affected. It is concluded that the plasma cortisol response to hypoglycemia gives a useful indication of ACTH release in steroid-treated patients provided that they have not recently received exogenous ACTH.", "contents": "The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration. The plasma cortisol response to hypoglycemia is widely used as a test of hypothalamic-pituitary-adrenal function. It was the aim of this study to determine whether this test gives a reliable indication of pituitary corticotropin (ACTH) release in patients recovering from adrenocortical suppression due to corticosteroid or ACTH therapy. The 16 patients who were studied (6 on more than one occasion) had received in excess of 5 mg predinisone or equivalent daily for over 12 months. The insulin tolerance tests were carried out 18 h after stopping steroid therapy. The tests were then repeated three to four days after adrenal function had been restored (as indicated by urinary oxogenic steroid excretion of greater than 35 mg/24 h) by zinc tetracosactrin administration. The ACTH response to hypoglycemia was significantly impaired in the steroid-treated group. However with the exception of one patient who had persistently elevated resting ACTH levels there was a significant correlation (P less than 0.01) between the maximum increments in plasma cortisol and ACTH during hypoglycemia. No significant difference in sensitivity to endogenous ACTH could be demonstrated between the steroid-treated group and 12 normal control subjects. Following ACTH administration the plasma ACTH and growth hormone responses to hypoglycemia were significantly reduced, but the response in plasma cortisol was not significantly affected. It is concluded that the plasma cortisol response to hypoglycemia gives a useful indication of ACTH release in steroid-treated patients provided that they have not recently received exogenous ACTH."} {"id": "PMID:168226", "title": "In vitro release and biosynthesis of tumor ACTH in ectopic ACTH producing tumors.", "content": "Tumor tissues obtained from 4 patients with the ectopic ACTH syndrome were studied for release and synthesis of tumor ACTH, using an in vitro incubation system. The effect of various agents on release of tumor ACTH was evaluated in three cases; beta-MSH released and adenosine 3',5'-monophosphate (cyclic AMP) formed in the tissue were determined in one. Biosynthetic experiments using labeled amino acid incorporation were performed in two cases. Secretion of tumor ACTH was significantly stimulated in all cases by crude rat median eminence extract which was also effective in stimulating beta-MSH secretion associated with elevated tissue cyclic AMP levels in one. Addition of cyclic AMP and dibutyryl cyclic AMP caused a significant increase in release of both tumor ACTH and beta-MSH in one. Biogenic amines (norepinephrine and serotonin) markedly elevated tussie cyclic AMP levels without a corresponding increase of hormone release in one. Incorporation experiments revealed that 3H- or 14C-phenylalanine was incorporated into immunoreactive ACTH of a larger molecular size (big ACTH) in both cases by chromatographic procedures. However, biological activity of big ACTH was found to be undetectable by an in vivo steroidogenic assay. A mild tryptic digestion of the big forms resulted in the appearance of little ACTH to which the major radioactive peak shifted. These data suggest that the mechanism of release of tumor ACTH and beta-MSH is very similar to that of the pituitary, and that intracellular cyclic AMP may in part play some role in release of both hormones. It is also suggested that some ectopic ACTH producing tumors predominantly synthesize big ACTH, a possible precursor of ACTH, with less bioactivity.", "contents": "In vitro release and biosynthesis of tumor ACTH in ectopic ACTH producing tumors. Tumor tissues obtained from 4 patients with the ectopic ACTH syndrome were studied for release and synthesis of tumor ACTH, using an in vitro incubation system. The effect of various agents on release of tumor ACTH was evaluated in three cases; beta-MSH released and adenosine 3',5'-monophosphate (cyclic AMP) formed in the tissue were determined in one. Biosynthetic experiments using labeled amino acid incorporation were performed in two cases. Secretion of tumor ACTH was significantly stimulated in all cases by crude rat median eminence extract which was also effective in stimulating beta-MSH secretion associated with elevated tissue cyclic AMP levels in one. Addition of cyclic AMP and dibutyryl cyclic AMP caused a significant increase in release of both tumor ACTH and beta-MSH in one. Biogenic amines (norepinephrine and serotonin) markedly elevated tussie cyclic AMP levels without a corresponding increase of hormone release in one. Incorporation experiments revealed that 3H- or 14C-phenylalanine was incorporated into immunoreactive ACTH of a larger molecular size (big ACTH) in both cases by chromatographic procedures. However, biological activity of big ACTH was found to be undetectable by an in vivo steroidogenic assay. A mild tryptic digestion of the big forms resulted in the appearance of little ACTH to which the major radioactive peak shifted. These data suggest that the mechanism of release of tumor ACTH and beta-MSH is very similar to that of the pituitary, and that intracellular cyclic AMP may in part play some role in release of both hormones. It is also suggested that some ectopic ACTH producing tumors predominantly synthesize big ACTH, a possible precursor of ACTH, with less bioactivity."} {"id": "PMID:168227", "title": "The contribution of the zona fasciculata and glomerulosa to plasma 11-deoxycorticosterone levels in man.", "content": "Using a newly developed radioassay method, plasma 11-deoxycorticosterone (DOC) levels were studied in 6 human volunteers for diurnal variation and for response to ACTH, metyrapone, dexamethasone, and low or high dietary sodium. DOC reached its peak of 6.4 +/- 1.2 ng/100 ml at 8:00 AM, and its nadir of less than 1 ng/100 ml at midnight. Corresponding plasma cortisol values were 14.1 +/- 1.4 mug/100 ml and 5.9 +/- 1.3 mug/100 ml respectively. After intramuscular ACTH (Cortrosyn 0.25 mg), DOC rose to 28.7 +/- 1.8 ng/100 ml in 1 h. Dexamethasone treatment for 3 days reduced DOC to less than 1 ng/100 ml in all 6 subjects. Oral metyrapone for 24 h resulted in dramatically elevated DOC levels of 1568 +/- 183 ng/100 ml. High dietary sodium did not affect DOC levels which averaged 5.6 +/- 0.7 ng/100 ml. After 3 days of sodium restriction, DOC levels were unchanged at 4.8 +/- 0.5 ng/100 ml (P greater than 0.9) despite high plasma renin activity and elevated plasma and urinary aldosterone. Dexamethasone was then added, and the diet continued for a further 2 days. In contrast to the effect of dexamethasone during ad lib sodium intake, DOC was not suppressed but slightly elevated to 8.6 +/- 1.4 ng/100 ml (P = 0.01), whereas plasma aldosterone decreased from 32.9 +/- 1.5 to 22.1 +/- 2.1 ng/100 ml. Seven additional subjects underwent the same diet for 5 days without the addition of dexamethasone. There was no change in their DOC values. It is concluded that the zona fasciculata is the main source of DOC, but in the presence of dexamethasone a contribution from the zona glomerulosa during sodium depletion is uncovered.", "contents": "The contribution of the zona fasciculata and glomerulosa to plasma 11-deoxycorticosterone levels in man. Using a newly developed radioassay method, plasma 11-deoxycorticosterone (DOC) levels were studied in 6 human volunteers for diurnal variation and for response to ACTH, metyrapone, dexamethasone, and low or high dietary sodium. DOC reached its peak of 6.4 +/- 1.2 ng/100 ml at 8:00 AM, and its nadir of less than 1 ng/100 ml at midnight. Corresponding plasma cortisol values were 14.1 +/- 1.4 mug/100 ml and 5.9 +/- 1.3 mug/100 ml respectively. After intramuscular ACTH (Cortrosyn 0.25 mg), DOC rose to 28.7 +/- 1.8 ng/100 ml in 1 h. Dexamethasone treatment for 3 days reduced DOC to less than 1 ng/100 ml in all 6 subjects. Oral metyrapone for 24 h resulted in dramatically elevated DOC levels of 1568 +/- 183 ng/100 ml. High dietary sodium did not affect DOC levels which averaged 5.6 +/- 0.7 ng/100 ml. After 3 days of sodium restriction, DOC levels were unchanged at 4.8 +/- 0.5 ng/100 ml (P greater than 0.9) despite high plasma renin activity and elevated plasma and urinary aldosterone. Dexamethasone was then added, and the diet continued for a further 2 days. In contrast to the effect of dexamethasone during ad lib sodium intake, DOC was not suppressed but slightly elevated to 8.6 +/- 1.4 ng/100 ml (P = 0.01), whereas plasma aldosterone decreased from 32.9 +/- 1.5 to 22.1 +/- 2.1 ng/100 ml. Seven additional subjects underwent the same diet for 5 days without the addition of dexamethasone. There was no change in their DOC values. It is concluded that the zona fasciculata is the main source of DOC, but in the presence of dexamethasone a contribution from the zona glomerulosa during sodium depletion is uncovered."} {"id": "PMID:168228", "title": "Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man.", "content": "Plasma ACTH levels after oral and iv metyrapone administration were studied in 7 and 5 healthy women respectively both under basal conditions and after a 4-day treatment with metergoline, a specific antiserotoninergic agent. In 3 additional women, the effects of methysergide, another antiserotoninergic drug, on the plasma ACTH rise induced by oral metyrapone, were evaluated. A significant lowering of the plasma ACTH levels attained after either oral or iv metyrapone was observed following metergoline administration: 149+/-64.3 vs 239+/-49.1 pg/ml (mean peak values), P less than 0.05 in the oral test and 331+/-19.7 vs 221+/-19.5 pg/ml, P less than 0.02 in the iv test. The fall of plasma cortisol caused by metyrapone was comparable before and after the antiserotoninergic treatment. An interference of metergoline in the ACTH radioimmunoassay was also excluded. After metergoline administration, a slight reduction in the baseline plasma ACTH values was noted: 79+/-7.7 vs 67+/-7.7 pg/ml (NS). A decrease, however not statistically significant, of the metyrapone-induced plasma ACTH elevation occured after methysergide administration: 421+/-150.7 vs 344+/-135.1 pg/ml. These results can be interpreted as indicating that antiserotoninergic treatment caused an inhibition of hypophysial ACTH release in response to metyrapone. Caution is recommended, however, before concluding, on the basis of these findings, that serotonin as such plays a physiological stimulating role on ACTH secretion.", "contents": "Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man. Plasma ACTH levels after oral and iv metyrapone administration were studied in 7 and 5 healthy women respectively both under basal conditions and after a 4-day treatment with metergoline, a specific antiserotoninergic agent. In 3 additional women, the effects of methysergide, another antiserotoninergic drug, on the plasma ACTH rise induced by oral metyrapone, were evaluated. A significant lowering of the plasma ACTH levels attained after either oral or iv metyrapone was observed following metergoline administration: 149+/-64.3 vs 239+/-49.1 pg/ml (mean peak values), P less than 0.05 in the oral test and 331+/-19.7 vs 221+/-19.5 pg/ml, P less than 0.02 in the iv test. The fall of plasma cortisol caused by metyrapone was comparable before and after the antiserotoninergic treatment. An interference of metergoline in the ACTH radioimmunoassay was also excluded. After metergoline administration, a slight reduction in the baseline plasma ACTH values was noted: 79+/-7.7 vs 67+/-7.7 pg/ml (NS). A decrease, however not statistically significant, of the metyrapone-induced plasma ACTH elevation occured after methysergide administration: 421+/-150.7 vs 344+/-135.1 pg/ml. These results can be interpreted as indicating that antiserotoninergic treatment caused an inhibition of hypophysial ACTH release in response to metyrapone. Caution is recommended, however, before concluding, on the basis of these findings, that serotonin as such plays a physiological stimulating role on ACTH secretion."} {"id": "PMID:168229", "title": "Plasma aldosterone response to low dose ACTH stimulation.", "content": "The brief (60-min) infusion of a small amount (1.25 mug) of ACTH into 7 normal subjects on an unrestricted sodium intake resulted in a vigorous plasma aldosterone response in each case. This finding suggests that physiologic fluctuations in ACTH may significantly alter aldosterone secretion in normal man.", "contents": "Plasma aldosterone response to low dose ACTH stimulation. The brief (60-min) infusion of a small amount (1.25 mug) of ACTH into 7 normal subjects on an unrestricted sodium intake resulted in a vigorous plasma aldosterone response in each case. This finding suggests that physiologic fluctuations in ACTH may significantly alter aldosterone secretion in normal man."} {"id": "PMID:168230", "title": "Secretory regulation of endocrine pancreas: Cyclic AMP and glucagon secretion.", "content": "Activation of adrenergic beta receptors has been found to stimulate insulin release in vitro that may be mediated through the augmentation of cyclic AMP in the beta cell. The activation of adrenergic alpha receptors in the beta cell inhibits the insulin release. The present studies have shown that isoproterenol (0.62 mug/ml) and sodium dibutyryl cyclic AMP (50 mug/ml) stimulate the insulin secretion and inhibit the glucagon secretion in the presence of 50 mg/100 ml glucose by the isolated pancreatic perfusion of the rat, while norepinephrine (0.5 mug/ml) inhibits the insulin secretion induced by 150 mg/100 ml glucose and stimulates the glucaton secretion. Theophylline (50 mug/ml) does not stimulate the insulin and the glucagon secretion. When norepinephrine is added to theophylline, the output of glucagon does not occur. From these results it can be deduced that the pancreatic alpha cell function may be inhibited by elevation of intracellular cyclic AMP, in contrast to the beta cell function which is stimulated by an increment of cyclic AMP.", "contents": "Secretory regulation of endocrine pancreas: Cyclic AMP and glucagon secretion. Activation of adrenergic beta receptors has been found to stimulate insulin release in vitro that may be mediated through the augmentation of cyclic AMP in the beta cell. The activation of adrenergic alpha receptors in the beta cell inhibits the insulin release. The present studies have shown that isoproterenol (0.62 mug/ml) and sodium dibutyryl cyclic AMP (50 mug/ml) stimulate the insulin secretion and inhibit the glucagon secretion in the presence of 50 mg/100 ml glucose by the isolated pancreatic perfusion of the rat, while norepinephrine (0.5 mug/ml) inhibits the insulin secretion induced by 150 mg/100 ml glucose and stimulates the glucaton secretion. Theophylline (50 mug/ml) does not stimulate the insulin and the glucagon secretion. When norepinephrine is added to theophylline, the output of glucagon does not occur. From these results it can be deduced that the pancreatic alpha cell function may be inhibited by elevation of intracellular cyclic AMP, in contrast to the beta cell function which is stimulated by an increment of cyclic AMP."} {"id": "PMID:168231", "title": "Stimulation of osmotic water flow in toad bladder by prostaglandin E1. Evidence for different compartments of cyclic AMP.", "content": "The effect of prostaglandin E1 (PGE1) on osmotic water flow across toad bladder and cyclic AMP content of the mucosal epithelial cells has been determined under basal conditions and in the presence of either theophylline or antidiuretic hormone (ADH); Under basal conditions and with PGE1 concentrations from 10(-8) to 10(-5) M no evidence of stimulation of water flow was observed, and with 10(-7) M PGE1 a significant inhibition was foundmcyclic AMP content under control conditions was 8 pmol/mg protein. It was 9 at 10(-8) M PGE1, 13 at 10(-7) M, 16 at 10(-6) M, and 23 at 10(-5) M. In the presence of theophylline, 10(-8) and 10(-7) M PGE1 inhibited the theophylline-induced water flow as expected. In contrast, 10(-6) and 10(-5) M PGE1 enhanced the rate of water flow. Theophylline increased cyclic AMP content from 8 to 18 pmol/mg protein. PGE1 in the presence of theophylline caused marked increases in cyclic AMP content; The content was 23 at 10(-7) M, 41 at 10(-6) M, and 130 at 10(-5) M; Thus PGE1 stimulates theophylline-induced water flow at cyclic AMP concentrations somewhere between 23 and 41 pmol/mg. Further evidence along these lines was obtained from experiments in which the effects of PGE1 on ADH-induced water flow were studied. Inhibitory effects of PGE1 were not observed at concentrations of PGE1 which raised the level of intracellular cyclic AMP to 30 pmol/mg protein or higher. These results were obtained despite the fact that all four concentrations of PGE1 tested were found capable of inhibiting ADH-induced water flow under appropriate conditions or, in other words, were inhibiting the adenylate cyclase controlling water flow, Thus the increase in cyclic AMP content in response to PGE1 is not derived from this enzyme. Thus the stimulation of water flow by PGE1 in the presence of theophylline is thought to be caused by cyclic AMP spilling over from one compartment to the water flow compartment. No evidence was obtained to directly suggest spillover into the sodium transport compartment. Furthermore evidence is discussed to suggest that most of the cyclic AMP generated in the tissue does not originate from the enzyme controlling sodium transport. As cyclic AMP-stimulated water flow and sodium transport are thought to occur in one cell type, the granular cells, distinct pools of cyclic AMP are thought to be present in one and the same cell type. Thus one pool controls water flow and one controls sodium transport. With high concentrations of PGE1 in the presence of theophylline or high concentrations of ADH, the adenylate cyclase responsible for water flow is inhibited; However, PGE1 can stimulate a tissue adenylate cyclase to sufficiently high levels that cyclic AMP spills over into the \"water flow compartment\" and thus stimulates water flow.", "contents": "Stimulation of osmotic water flow in toad bladder by prostaglandin E1. Evidence for different compartments of cyclic AMP. The effect of prostaglandin E1 (PGE1) on osmotic water flow across toad bladder and cyclic AMP content of the mucosal epithelial cells has been determined under basal conditions and in the presence of either theophylline or antidiuretic hormone (ADH); Under basal conditions and with PGE1 concentrations from 10(-8) to 10(-5) M no evidence of stimulation of water flow was observed, and with 10(-7) M PGE1 a significant inhibition was foundmcyclic AMP content under control conditions was 8 pmol/mg protein. It was 9 at 10(-8) M PGE1, 13 at 10(-7) M, 16 at 10(-6) M, and 23 at 10(-5) M. In the presence of theophylline, 10(-8) and 10(-7) M PGE1 inhibited the theophylline-induced water flow as expected. In contrast, 10(-6) and 10(-5) M PGE1 enhanced the rate of water flow. Theophylline increased cyclic AMP content from 8 to 18 pmol/mg protein. PGE1 in the presence of theophylline caused marked increases in cyclic AMP content; The content was 23 at 10(-7) M, 41 at 10(-6) M, and 130 at 10(-5) M; Thus PGE1 stimulates theophylline-induced water flow at cyclic AMP concentrations somewhere between 23 and 41 pmol/mg. Further evidence along these lines was obtained from experiments in which the effects of PGE1 on ADH-induced water flow were studied. Inhibitory effects of PGE1 were not observed at concentrations of PGE1 which raised the level of intracellular cyclic AMP to 30 pmol/mg protein or higher. These results were obtained despite the fact that all four concentrations of PGE1 tested were found capable of inhibiting ADH-induced water flow under appropriate conditions or, in other words, were inhibiting the adenylate cyclase controlling water flow, Thus the increase in cyclic AMP content in response to PGE1 is not derived from this enzyme. Thus the stimulation of water flow by PGE1 in the presence of theophylline is thought to be caused by cyclic AMP spilling over from one compartment to the water flow compartment. No evidence was obtained to directly suggest spillover into the sodium transport compartment. Furthermore evidence is discussed to suggest that most of the cyclic AMP generated in the tissue does not originate from the enzyme controlling sodium transport. As cyclic AMP-stimulated water flow and sodium transport are thought to occur in one cell type, the granular cells, distinct pools of cyclic AMP are thought to be present in one and the same cell type. Thus one pool controls water flow and one controls sodium transport. With high concentrations of PGE1 in the presence of theophylline or high concentrations of ADH, the adenylate cyclase responsible for water flow is inhibited; However, PGE1 can stimulate a tissue adenylate cyclase to sufficiently high levels that cyclic AMP spills over into the \"water flow compartment\" and thus stimulates water flow."} {"id": "PMID:168232", "title": "Studies of the elevated extracellular concentration of cyclic AMP in uremic man.", "content": "This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured. Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of \"metabolic clearance.\" In addition, the \"plasms production rate\" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects. It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreases metabolic clearance, and (c) increased production of plasma cyclic AMP.", "contents": "Studies of the elevated extracellular concentration of cyclic AMP in uremic man. This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured. Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of \"metabolic clearance.\" In addition, the \"plasms production rate\" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects. It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreases metabolic clearance, and (c) increased production of plasma cyclic AMP."} {"id": "PMID:168233", "title": "Inhibitory effect of dietary iodine on the thyroid adenylate cyclase response to thyrotropin in the hypophysectomized rat.", "content": "In hypophysectomized rats given dietary regimens either rich or deficient in iodine, the increase in thyroid cyclic AMP concentration induced acutely by a single dose of TSH was significantly less in iodine-enriched than in iodine-deficient animals. Direct assays revealed that this difference was because the thyroid adenylate cyclase response to TSH was less in the iodine-enriched animals, phosphodiesterase activity being no different in the two groups. This effect may explain the inhibitory action of dietary iodine enrichment on diverse functional and anatomical responses of the thyroid to TSH.", "contents": "Inhibitory effect of dietary iodine on the thyroid adenylate cyclase response to thyrotropin in the hypophysectomized rat. In hypophysectomized rats given dietary regimens either rich or deficient in iodine, the increase in thyroid cyclic AMP concentration induced acutely by a single dose of TSH was significantly less in iodine-enriched than in iodine-deficient animals. Direct assays revealed that this difference was because the thyroid adenylate cyclase response to TSH was less in the iodine-enriched animals, phosphodiesterase activity being no different in the two groups. This effect may explain the inhibitory action of dietary iodine enrichment on diverse functional and anatomical responses of the thyroid to TSH."} {"id": "PMID:168234", "title": "Comparison of the sensitivity of human embryo kidney cells, HeLa cells, and WI38 cells for the primary isolation of viruses from the eye.", "content": "A comparison has been made of the efficiency of human embryo kidney (HEK) cills, HeLa cells, and WI38 cells for the isolation of viruses from the eyes of patients suffering from acute conjunctivitis or keratoconjunctivitis. From a total of 99 specimens 21 adenoviruses (serotypes 3, 4, 7, 8, and 13) were isolated in HEK cells, eight (serotypes 3 and 8) in HeLa cells, and four (serotype 3) in WI38 cells. Of the ten herpes simplex viruses isolated nine were recovered in HEK cells, seven in WI38 cells, and none in HeLa cells. The combination of HeLa cells and WI38 cells is not considered an adequate alternative to the difficult-to-obtain HEK cells for the isolation of viruses from the eye.", "contents": "Comparison of the sensitivity of human embryo kidney cells, HeLa cells, and WI38 cells for the primary isolation of viruses from the eye. A comparison has been made of the efficiency of human embryo kidney (HEK) cills, HeLa cells, and WI38 cells for the isolation of viruses from the eyes of patients suffering from acute conjunctivitis or keratoconjunctivitis. From a total of 99 specimens 21 adenoviruses (serotypes 3, 4, 7, 8, and 13) were isolated in HEK cells, eight (serotypes 3 and 8) in HeLa cells, and four (serotype 3) in WI38 cells. Of the ten herpes simplex viruses isolated nine were recovered in HEK cells, seven in WI38 cells, and none in HeLa cells. The combination of HeLa cells and WI38 cells is not considered an adequate alternative to the difficult-to-obtain HEK cells for the isolation of viruses from the eye."} {"id": "PMID:168235", "title": "Human brain in tissue culture. III. PML-SV40-induced transformation of brain cells and establishment of permanent lines.", "content": "Cells from explants and monolayer subcultures of adult human brain obtained from biopsies or autopsies of ten multiple sclerosis (MS) cases, one case each of Jakob-Creutzfeld (JC) and amyotrophic lateral sclerosis (ALS) and three cases with no central nervous system (CNS) involvement were transformed with PML-SV40 virus. Transformation was effected to establish permanent lines of these particular adult brain cells so that sufficient quantities would be available for other research projects. The procedure previously used to transform human fibroblasts (Koprowski et al., '62) was successfully applied to human brain cells. The success of transformation was dependent on the growth condition of the cultures at the time of infection. Events occurring after viral infection and during the pre-transformation and the post-transformation phases are described.", "contents": "Human brain in tissue culture. III. PML-SV40-induced transformation of brain cells and establishment of permanent lines. Cells from explants and monolayer subcultures of adult human brain obtained from biopsies or autopsies of ten multiple sclerosis (MS) cases, one case each of Jakob-Creutzfeld (JC) and amyotrophic lateral sclerosis (ALS) and three cases with no central nervous system (CNS) involvement were transformed with PML-SV40 virus. Transformation was effected to establish permanent lines of these particular adult brain cells so that sufficient quantities would be available for other research projects. The procedure previously used to transform human fibroblasts (Koprowski et al., '62) was successfully applied to human brain cells. The success of transformation was dependent on the growth condition of the cultures at the time of infection. Events occurring after viral infection and during the pre-transformation and the post-transformation phases are described."} {"id": "PMID:168236", "title": "Human brain in tissue culture. IV. Morphological characteristics.", "content": "The morphology of cells from normal and diseased brains and PML-SV40 transformed brain cells grown on glass cover slips in cultures is described. Seven types of cells are identifiable, four of which are probably of mesenchymal origin whereas the remaining three are neurologlial. A classification on the basis of the morphologic features is presented.", "contents": "Human brain in tissue culture. IV. Morphological characteristics. The morphology of cells from normal and diseased brains and PML-SV40 transformed brain cells grown on glass cover slips in cultures is described. Seven types of cells are identifiable, four of which are probably of mesenchymal origin whereas the remaining three are neurologlial. A classification on the basis of the morphologic features is presented."} {"id": "PMID:168237", "title": "Hormonal dissociation of limbic lesion effects on shuttle box avoidance in rats.", "content": "Rats with septal or hippocampal lesions, relative to normal rats, showed facilitated acquisition of a shuttle box avoidance response. The rats with septal lesions were also highly resistant to extinction compared with normal rats. When the same lesion effects were examined in hypophysectiomized rats, the animals with septal lesions continued to show facilitated performance, and those rats with hippocampal lesions performed no differently than nonoperated control animals. These findings are consistent with the hypothesis that the facilitated avoidance performance found in rats with hippocampal lesions is attributable to lesion-induced changes in hypophyseal activity, but similar changes induced by septal lesions are not.", "contents": "Hormonal dissociation of limbic lesion effects on shuttle box avoidance in rats. Rats with septal or hippocampal lesions, relative to normal rats, showed facilitated acquisition of a shuttle box avoidance response. The rats with septal lesions were also highly resistant to extinction compared with normal rats. When the same lesion effects were examined in hypophysectiomized rats, the animals with septal lesions continued to show facilitated performance, and those rats with hippocampal lesions performed no differently than nonoperated control animals. These findings are consistent with the hypothesis that the facilitated avoidance performance found in rats with hippocampal lesions is attributable to lesion-induced changes in hypophyseal activity, but similar changes induced by septal lesions are not."} {"id": "PMID:168239", "title": "IgE antipolymyxin B antibody formation in a T cell-depleted bone marrow transplant patient.", "content": "The production of IgE-class antibody specific for polymyxin B is documented in an 18-year-old white female acute myelocytic leukemic patient in relapse. The patient was rendered T cell-deficient by total body X-irradiation and antihuman thymocyte globulin for the purpose of bone marrow transplatation. Thereafter, symptoms of nasal congestion, rhinorrhea, and perinasal urtication produced by topical application of a polymyxin solution were noted. Reaginic activity mediated by an IgE antibody against polymyxin is documented by Prausnbitz-K\u00fcstner-type passive transfer reactions and by an indirect hemagglutination technique developed for these studies. The occurrence of type I hypersensitivity to this topical antibiotic is rare. It is speculated that pharmaceuticals normally having a low sensitizing potential might demonstrate increased reaginic immunogenicity in a spontaneously or iatrogenically T cell-depleted patient.", "contents": "IgE antipolymyxin B antibody formation in a T cell-depleted bone marrow transplant patient. The production of IgE-class antibody specific for polymyxin B is documented in an 18-year-old white female acute myelocytic leukemic patient in relapse. The patient was rendered T cell-deficient by total body X-irradiation and antihuman thymocyte globulin for the purpose of bone marrow transplatation. Thereafter, symptoms of nasal congestion, rhinorrhea, and perinasal urtication produced by topical application of a polymyxin solution were noted. Reaginic activity mediated by an IgE antibody against polymyxin is documented by Prausnbitz-K\u00fcstner-type passive transfer reactions and by an indirect hemagglutination technique developed for these studies. The occurrence of type I hypersensitivity to this topical antibiotic is rare. It is speculated that pharmaceuticals normally having a low sensitizing potential might demonstrate increased reaginic immunogenicity in a spontaneously or iatrogenically T cell-depleted patient."} {"id": "PMID:168247", "title": "Acid-beta-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation.", "content": "A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase mehtod, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observed in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in beta-glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequenco of the pathologic process affecting the ultrastructural-chemical organization of the organelle.", "contents": "Acid-beta-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation. A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase mehtod, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observed in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in beta-glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequenco of the pathologic process affecting the ultrastructural-chemical organization of the organelle."} {"id": "PMID:168248", "title": "The immune response to infection with vaccinia virus in mice. I. Infection and the production of antibody neutralizing cell-associated and cell-free virus.", "content": "The onset, duration and magnitude of antibody responses to a poxvirus infection were examined. Mice were inoculated intravenously with the WR strain of vaccinia virus and developed pocks on their tails. The number of pocks was related to the size of the inoculum. Virus was detectable in the spleen and infected mice were subsequently immune to intravenous and intra-nasal challenge. Sera of infected animals neutralized both cell-free and cell-associated virus. Antibody against cell-free virus appeared first; maximum titres were reached sooner but were lower than those of antibody neutralizing cell-associated virus. Titres remained high for at least 100 days after infection.", "contents": "The immune response to infection with vaccinia virus in mice. I. Infection and the production of antibody neutralizing cell-associated and cell-free virus. The onset, duration and magnitude of antibody responses to a poxvirus infection were examined. Mice were inoculated intravenously with the WR strain of vaccinia virus and developed pocks on their tails. The number of pocks was related to the size of the inoculum. Virus was detectable in the spleen and infected mice were subsequently immune to intravenous and intra-nasal challenge. Sera of infected animals neutralized both cell-free and cell-associated virus. Antibody against cell-free virus appeared first; maximum titres were reached sooner but were lower than those of antibody neutralizing cell-associated virus. Titres remained high for at least 100 days after infection."} {"id": "PMID:168249", "title": "Epidemiological studies of Epstein-Barr herpesvirus infection in Western Australia.", "content": "In a study of a Caucasian population in Western Australia the prevalence of antibodies to Epstein-Barr virus (EBV) was 41% in the 9- to 10-year age group, 80% in the 16 to 19-year age group and 92% in young adults. The age-specific annual seroconversion rates indicated two peaks of primary EBV infection in the population studied - one under 5 years of age and the other at adolescence. The geometric mean titre rose with age, from 23 at 5-6 years to 53 at 36-40 years. It was shown that in 73 families studied there was evidence of probable spread of EBV infection among siblings, particularly between those of the same sex. Serological study of patients with infectious mononucleosis indicated that 100% of those examined had antibody to EBV and the geometric mean titre was elevated to 210. Rising titres and seroconversion was demonstrated in these patients together with successful establishment of EBV-carrying cell lines from the peripheral blood in two-thirds of the cases.", "contents": "Epidemiological studies of Epstein-Barr herpesvirus infection in Western Australia. In a study of a Caucasian population in Western Australia the prevalence of antibodies to Epstein-Barr virus (EBV) was 41% in the 9- to 10-year age group, 80% in the 16 to 19-year age group and 92% in young adults. The age-specific annual seroconversion rates indicated two peaks of primary EBV infection in the population studied - one under 5 years of age and the other at adolescence. The geometric mean titre rose with age, from 23 at 5-6 years to 53 at 36-40 years. It was shown that in 73 families studied there was evidence of probable spread of EBV infection among siblings, particularly between those of the same sex. Serological study of patients with infectious mononucleosis indicated that 100% of those examined had antibody to EBV and the geometric mean titre was elevated to 210. Rising titres and seroconversion was demonstrated in these patients together with successful establishment of EBV-carrying cell lines from the peripheral blood in two-thirds of the cases."} {"id": "PMID:168250", "title": "The survival of foot-and-mouth disease virus in open air conditions.", "content": "The influence of the Open Air Factor (OAF) and daylight on the survival of foot-and-mouth disease (FMD) virus held as captured aerosols on spider microthreads has been investigated. Virus inactivation due to OAF was slight. Similarly, the effect of daylight on the survival of virus was not marked. The results are discussed in relation to the airborne spread of FMD virus in nature.", "contents": "The survival of foot-and-mouth disease virus in open air conditions. The influence of the Open Air Factor (OAF) and daylight on the survival of foot-and-mouth disease (FMD) virus held as captured aerosols on spider microthreads has been investigated. Virus inactivation due to OAF was slight. Similarly, the effect of daylight on the survival of virus was not marked. The results are discussed in relation to the airborne spread of FMD virus in nature."} {"id": "PMID:168251", "title": "The quantitative bacteriology of some commercial bivalve shellfish entering British markets.", "content": "Incidents of non-specific illness associated with the consumption of oysters have highlighted the lack of published information on the bacteriology of shellfish suitable for consumption. Investigations showed that the majority of molluscan shellfish entering English markets conform to the accepted standard of less than 5 Escherichia coli/ml. tissue. The numbers of E. coli were related to the sanitary quality of the growing area but no relation could be established between numbers of E. coli and coliforms, faecal streptococci or Clostridium welchii. The numbers of non-specific bacteria varied considerably but shellfish from sources associated with non-specific illness yielded relatively high counts at 37 degrees C. The results showed that there was no justification for a standard based on total plate counts, which often exceeded 10(6)/g. Such a standard would have to be coupled with spoilage or the incidence of non-specific illness. The relation between the numbers of non-specific bacteria growing at 20 and 37 degrees C. appears to be a useful measure for assessing the likelihood that raw shellfish are a public health risk.", "contents": "The quantitative bacteriology of some commercial bivalve shellfish entering British markets. Incidents of non-specific illness associated with the consumption of oysters have highlighted the lack of published information on the bacteriology of shellfish suitable for consumption. Investigations showed that the majority of molluscan shellfish entering English markets conform to the accepted standard of less than 5 Escherichia coli/ml. tissue. The numbers of E. coli were related to the sanitary quality of the growing area but no relation could be established between numbers of E. coli and coliforms, faecal streptococci or Clostridium welchii. The numbers of non-specific bacteria varied considerably but shellfish from sources associated with non-specific illness yielded relatively high counts at 37 degrees C. The results showed that there was no justification for a standard based on total plate counts, which often exceeded 10(6)/g. Such a standard would have to be coupled with spoilage or the incidence of non-specific illness. The relation between the numbers of non-specific bacteria growing at 20 and 37 degrees C. appears to be a useful measure for assessing the likelihood that raw shellfish are a public health risk."} {"id": "PMID:168252", "title": "Hypersensitivity in cattle after foot-and-mouth disease vaccination: response to hydroxpropylmethylcellulose.", "content": "Intravenous provocation (IVP) tests demonstrated that hydroxypropylmethylcellulose (MC) was able to elicit anaphylactic signs in cattle vaccinated with foot-and-mouth disease (FMD) vaccine produced at one centre but not with similar vaccine produced at another. The former vaccine also provoked serum reagins which were demonstrated by passive cutaneous anaphylaxis (PCA) tests in goats. Reaginic sera which reacted specifically with MC were used in PCA tests to screen samples taken serially from the vaccine production lines. The reactions observed suggested that a substance with MC or similar specificity was present in the antifoaming agent routinely added to vaccines.", "contents": "Hypersensitivity in cattle after foot-and-mouth disease vaccination: response to hydroxpropylmethylcellulose. Intravenous provocation (IVP) tests demonstrated that hydroxypropylmethylcellulose (MC) was able to elicit anaphylactic signs in cattle vaccinated with foot-and-mouth disease (FMD) vaccine produced at one centre but not with similar vaccine produced at another. The former vaccine also provoked serum reagins which were demonstrated by passive cutaneous anaphylaxis (PCA) tests in goats. Reaginic sera which reacted specifically with MC were used in PCA tests to screen samples taken serially from the vaccine production lines. The reactions observed suggested that a substance with MC or similar specificity was present in the antifoaming agent routinely added to vaccines."} {"id": "PMID:168253", "title": "Specific mitogenic activity of 8-Br-guanosine 3',5'-monophosphate (Br-cyclic GMP) on B lymphocytes.", "content": "8-Br-cyclic GMP has been found to be a specific B cell mitogen; it triggers athymic nude mice spleen cells and \"B mice\" spleen cells, nylon adherent, anti-theta and complement-treated cells to proliferate. It does not stimulate thymocytes or purified T cells. The kinetics of the response to Br-cyclic GMP and LPS are almost identical. The mitogenic effect of LPS and Br-cyclic GMP is additive when the two mitogens are given together to cells. Spleen cells (C3H/HeJ strain) that did not respond to LPS were triggered by Br-cyclic GMP to make DNA. In order to achieve maximal stimulation by Br-cyclic GMP, the drug had to be in contact with the cells for more than 24 hr. Br-cyclic GMP was found to be mitogenic for spleen cells from five different mouse strains, but not for human leukocytes. DB-cyclic AMP was found to inhibit the DNA synthesis of T lymphocytes after they interacted with Con A; DB-cyclic AMP had no effect on the ability of the B lymphocytes to be transformed by LPS. The differential effects of cyclic nucleotides on B vs. T lymphocytes are discussed.", "contents": "Specific mitogenic activity of 8-Br-guanosine 3',5'-monophosphate (Br-cyclic GMP) on B lymphocytes. 8-Br-cyclic GMP has been found to be a specific B cell mitogen; it triggers athymic nude mice spleen cells and \"B mice\" spleen cells, nylon adherent, anti-theta and complement-treated cells to proliferate. It does not stimulate thymocytes or purified T cells. The kinetics of the response to Br-cyclic GMP and LPS are almost identical. The mitogenic effect of LPS and Br-cyclic GMP is additive when the two mitogens are given together to cells. Spleen cells (C3H/HeJ strain) that did not respond to LPS were triggered by Br-cyclic GMP to make DNA. In order to achieve maximal stimulation by Br-cyclic GMP, the drug had to be in contact with the cells for more than 24 hr. Br-cyclic GMP was found to be mitogenic for spleen cells from five different mouse strains, but not for human leukocytes. DB-cyclic AMP was found to inhibit the DNA synthesis of T lymphocytes after they interacted with Con A; DB-cyclic AMP had no effect on the ability of the B lymphocytes to be transformed by LPS. The differential effects of cyclic nucleotides on B vs. T lymphocytes are discussed."} {"id": "PMID:168254", "title": "Non-T cell killing of mammary tumor cells by spleen cells: secretion of antibody and recruitment of cells.", "content": "Both T cell-mediated killing and non-T cell-mediated killing of target MTV-induced mammary tumor cells can be detected in microcytotoxicity assay tests of spleen cells from mice immunologically responsive to either the histocompatibility antigens or the virus-associated antigens of the target cells. The non-T cell-mediated cytotoxicity is antibody-dependent; otherwise inactive cells (null cells) can be recruited to activity by target cell-specific factors obtained from the supernatant of short-term cultures of sensitized B cells or provided by the introduction of a small number of sensitized B cells to the wells of the assay plate.", "contents": "Non-T cell killing of mammary tumor cells by spleen cells: secretion of antibody and recruitment of cells. Both T cell-mediated killing and non-T cell-mediated killing of target MTV-induced mammary tumor cells can be detected in microcytotoxicity assay tests of spleen cells from mice immunologically responsive to either the histocompatibility antigens or the virus-associated antigens of the target cells. The non-T cell-mediated cytotoxicity is antibody-dependent; otherwise inactive cells (null cells) can be recruited to activity by target cell-specific factors obtained from the supernatant of short-term cultures of sensitized B cells or provided by the introduction of a small number of sensitized B cells to the wells of the assay plate."} {"id": "PMID:168255", "title": "Enhanced destruction of lymphoid cell lines by peripheral blood leukocytes taken from patients with acute infectious mononucleosis.", "content": "The cytotoxicity of peripheral blood leukocytes from normal human donors and from patients with EBV-associated infectious nomonucleosis (IM) has been determined for human lymphoid cell lines (LCL) containing Epstein-Barr virus (EBV) DNA. In a 51Cr release assay, mononuclear leukocytes from all donors are spontaneously cytotoxic. Leukocytes taken from patients within the first 2 weeks of overt IM are significantly more cytotoxic. This increased cytotoxicity declines to the spontaneous level as the disease progesses. The increase shows no correlation with the degree of lymphocytosis but a positive correlation with numbers of circulating atypical cells. The reaction is apparently not directed against histocompatability antigens, known EBV membrane antigens, or other characteristics of fresh human lymphoid cells. Susceptibility to damage is shared by bone marrow-derived (B) cell lines but not thymus derived (T) cell lines. EBV-gene products cannot be soley responsible for expression of the unknown characteristic. Transformation of B cells with EBV in vivo or in vitro, however, may trigger its expression", "contents": "Enhanced destruction of lymphoid cell lines by peripheral blood leukocytes taken from patients with acute infectious mononucleosis. The cytotoxicity of peripheral blood leukocytes from normal human donors and from patients with EBV-associated infectious nomonucleosis (IM) has been determined for human lymphoid cell lines (LCL) containing Epstein-Barr virus (EBV) DNA. In a 51Cr release assay, mononuclear leukocytes from all donors are spontaneously cytotoxic. Leukocytes taken from patients within the first 2 weeks of overt IM are significantly more cytotoxic. This increased cytotoxicity declines to the spontaneous level as the disease progesses. The increase shows no correlation with the degree of lymphocytosis but a positive correlation with numbers of circulating atypical cells. The reaction is apparently not directed against histocompatability antigens, known EBV membrane antigens, or other characteristics of fresh human lymphoid cells. Susceptibility to damage is shared by bone marrow-derived (B) cell lines but not thymus derived (T) cell lines. EBV-gene products cannot be soley responsible for expression of the unknown characteristic. Transformation of B cells with EBV in vivo or in vitro, however, may trigger its expression"} {"id": "PMID:168258", "title": "The control exerted by thymic hormone (THF) on cellular cAMP levels and immune reactivity of spleen cells in the MLC assay.", "content": "We have shown previously that THF induces immunocompetence in lymphoid cells through the control of cellular cAMP levels and DNA synthesis. By the use of a one-way MLC assay it was now shown that the exposure of spleen cells to THF is accompanied by an increase, in the proliferative response of the responding cells. These effects are mediated by regulation of cellular levels of cAMP during the course of the MLC response. Thus, substances which modify cellular levels of cAMP such as DBcAMP, theophylline, and imidazole change the reactivity of cells exposed to THF in the MLC assay. It was also found here that cellular cAMP levels are critical in controlling the reactivity of normal spleen cells in the absence of THF. It is suggested that THF increases the number of competent cells in the spleen cell population capable of responding to antigenic stimulation in the MLC assay.", "contents": "The control exerted by thymic hormone (THF) on cellular cAMP levels and immune reactivity of spleen cells in the MLC assay. We have shown previously that THF induces immunocompetence in lymphoid cells through the control of cellular cAMP levels and DNA synthesis. By the use of a one-way MLC assay it was now shown that the exposure of spleen cells to THF is accompanied by an increase, in the proliferative response of the responding cells. These effects are mediated by regulation of cellular levels of cAMP during the course of the MLC response. Thus, substances which modify cellular levels of cAMP such as DBcAMP, theophylline, and imidazole change the reactivity of cells exposed to THF in the MLC assay. It was also found here that cellular cAMP levels are critical in controlling the reactivity of normal spleen cells in the absence of THF. It is suggested that THF increases the number of competent cells in the spleen cell population capable of responding to antigenic stimulation in the MLC assay."} {"id": "PMID:168259", "title": "Secondary cell-mediated cytotoxic response to syngeneic mouse tumor challenge.", "content": "When C57BL/6 mice previously immunized with murine sarcoma virus (MSV) were challenged with a Rauscher virus-induced lymphoma, RBL-5, a secondary cell-mediated cytotoxic response could be detected by the Cr release cytotoxicity assay. The level and distribution of the secondary cytotoxic response was affected by the route of challenge. Animals injected i.p. demonstrated a high level of cytotoxicity in the peritoneal exudate cells 3 days after challenge and subsequently cytotoxicity was detected in most lymphoid organs, although at lower levels. However, when the animals were challenged intramuscularly in the leg, the response was not detected as rapidly and furthermore cytotoxic lymphocytes were found only in the draining lymph node and not in other lymphoid organs. Treatment of the effector cells with anti-theta and complement showed the secondary response to be predominately dependent on T cells. In addition, the cytotoxicity was specific in that cells lacking cross-reacting antigens were not killed by these attacker cells from mice undergoing a secondary response.", "contents": "Secondary cell-mediated cytotoxic response to syngeneic mouse tumor challenge. When C57BL/6 mice previously immunized with murine sarcoma virus (MSV) were challenged with a Rauscher virus-induced lymphoma, RBL-5, a secondary cell-mediated cytotoxic response could be detected by the Cr release cytotoxicity assay. The level and distribution of the secondary cytotoxic response was affected by the route of challenge. Animals injected i.p. demonstrated a high level of cytotoxicity in the peritoneal exudate cells 3 days after challenge and subsequently cytotoxicity was detected in most lymphoid organs, although at lower levels. However, when the animals were challenged intramuscularly in the leg, the response was not detected as rapidly and furthermore cytotoxic lymphocytes were found only in the draining lymph node and not in other lymphoid organs. Treatment of the effector cells with anti-theta and complement showed the secondary response to be predominately dependent on T cells. In addition, the cytotoxicity was specific in that cells lacking cross-reacting antigens were not killed by these attacker cells from mice undergoing a secondary response."} {"id": "PMID:168260", "title": "X chromosome-linked defect of CBA/HN mice in production of tumor-reactive naturally occurring IgM antibodies.", "content": "Tumor-reactive naturally occurring antibodies (NOA) could be readily detected in sera of many mouse strains including congenitally athymic (nude) and germ free (gf) mice. Mice of the CBA/HN strain, however, were found to possess low or undetectable levels of NOA against a wide range of tumor cell lines. Genetic studies indicated that the defect in production of tumor-reactive NOA in CBA/HN mice was largely determined by the absence of an X chromosome-linked gene and is probably similar to the known X chromosome defect of this mouse strain in their antibody response to thymus-independent antigens. In spite of the low level of tumor-reactive NOA, CBA/HN mice do not have a high incidence of spontaneous tumors. These findings suggest that if tumor reactive NOA are involved in immune surveillance against malignancy they are unlikely to act directly in a quantitative manner in the detection and elimination of autochthonous tumors.", "contents": "X chromosome-linked defect of CBA/HN mice in production of tumor-reactive naturally occurring IgM antibodies. Tumor-reactive naturally occurring antibodies (NOA) could be readily detected in sera of many mouse strains including congenitally athymic (nude) and germ free (gf) mice. Mice of the CBA/HN strain, however, were found to possess low or undetectable levels of NOA against a wide range of tumor cell lines. Genetic studies indicated that the defect in production of tumor-reactive NOA in CBA/HN mice was largely determined by the absence of an X chromosome-linked gene and is probably similar to the known X chromosome defect of this mouse strain in their antibody response to thymus-independent antigens. In spite of the low level of tumor-reactive NOA, CBA/HN mice do not have a high incidence of spontaneous tumors. These findings suggest that if tumor reactive NOA are involved in immune surveillance against malignancy they are unlikely to act directly in a quantitative manner in the detection and elimination of autochthonous tumors."} {"id": "PMID:168261", "title": "Analysis of specificity of poliovirus inhibitors with inhibitor-resistant mutants of a strain of type 1 poliovirus.", "content": "Attempts were made to analyze the specificity of inhibitory activities of normal bovine and equine sera to the Mahoney strain of type 1 poliovirus. A total of five inhibitory factors were postulated to explain the complicated results. Two of the three bovine inhibitors were identical in specificity to certain equine inhibitors despite differences in their mode of virus inactivation and their molecular size. In addition to this, inhibitors that could inactivate certain resistant mutants, but not the parent virus, were newly detected in a number of normal bovine and equine sera. Antigenic variation of the resistant mutants against equine sera containing an inhibitory factor h-11 was determined by means of the kinetic neutralization test by using both anti-Mahoney and anti-M-H11 sera. These results offer evidence that some inhibitors, at least in part, are indistinguishable from specific antibody.", "contents": "Analysis of specificity of poliovirus inhibitors with inhibitor-resistant mutants of a strain of type 1 poliovirus. Attempts were made to analyze the specificity of inhibitory activities of normal bovine and equine sera to the Mahoney strain of type 1 poliovirus. A total of five inhibitory factors were postulated to explain the complicated results. Two of the three bovine inhibitors were identical in specificity to certain equine inhibitors despite differences in their mode of virus inactivation and their molecular size. In addition to this, inhibitors that could inactivate certain resistant mutants, but not the parent virus, were newly detected in a number of normal bovine and equine sera. Antigenic variation of the resistant mutants against equine sera containing an inhibitory factor h-11 was determined by means of the kinetic neutralization test by using both anti-Mahoney and anti-M-H11 sera. These results offer evidence that some inhibitors, at least in part, are indistinguishable from specific antibody."} {"id": "PMID:168262", "title": "Immunopathology of mouse hepatitis virus type 3 infection. III. Clinical and virologic observation of a persistent viral infection.", "content": "Three types of viral sensitivity were observed in various mouse strains upon MHV3 infection: resistance, full susceptibility, and semisusceptibility. In the latter type, seen in several inbred strains including C3H, approximately 50% of the adult injected animals resisted to the acute disease. Most of the surviving mice, however, developed a chronic disease with a wasting syndrome and occurrence of paralysis. The chronic period of the disease was characterized by a persistent viral infection, since MHV3 virus was recovered from brain, liver, spleen, and lymph nodes throughout the evolution in most of the animals. In addition, a correlation was observed between the clinical evolution and the titer of virus tested 4 days after infection.", "contents": "Immunopathology of mouse hepatitis virus type 3 infection. III. Clinical and virologic observation of a persistent viral infection. Three types of viral sensitivity were observed in various mouse strains upon MHV3 infection: resistance, full susceptibility, and semisusceptibility. In the latter type, seen in several inbred strains including C3H, approximately 50% of the adult injected animals resisted to the acute disease. Most of the surviving mice, however, developed a chronic disease with a wasting syndrome and occurrence of paralysis. The chronic period of the disease was characterized by a persistent viral infection, since MHV3 virus was recovered from brain, liver, spleen, and lymph nodes throughout the evolution in most of the animals. In addition, a correlation was observed between the clinical evolution and the titer of virus tested 4 days after infection."} {"id": "PMID:168263", "title": "Expression of mouse mammary tumor viral polypeptides in milks and tissues.", "content": "A 14,000-dalton polypeptide (p14) from RIII murine mammary tumor virus (MMTV) has been isolated by column chromatography in 6 M GuHCl. Antiserum prepared in rabbits specifically precipitated 125I-labeled p14; in double antibody competition, radioimmunoassays performed with limiting amounts of antibody, both purified p14 and disrupted MMTV, competed specifically with labeled antigen. The expression of this MMTV type B virus antigen could be measured by competition radioimmunoassays in milks, mammary glands, tumors, and tissue culture cells. MMTV expression measured by p14 immunoassay correlated well with the spontaneous incidence of mammary adenocarcinomas in different murine strains but not with type C MuLV p30 antigen expression. Levels of MMTV gp52, the major type-B viral glycoprotein, corresponded to p14 levels, suggesting that their control is comparably regulated. Evidence that this low m.w. polypeptide is present in feral and inbred strains of widely differing geographic origin and in MMTV with apparently different biologic properties suggests surprising conservation of MMTV protein homology.", "contents": "Expression of mouse mammary tumor viral polypeptides in milks and tissues. A 14,000-dalton polypeptide (p14) from RIII murine mammary tumor virus (MMTV) has been isolated by column chromatography in 6 M GuHCl. Antiserum prepared in rabbits specifically precipitated 125I-labeled p14; in double antibody competition, radioimmunoassays performed with limiting amounts of antibody, both purified p14 and disrupted MMTV, competed specifically with labeled antigen. The expression of this MMTV type B virus antigen could be measured by competition radioimmunoassays in milks, mammary glands, tumors, and tissue culture cells. MMTV expression measured by p14 immunoassay correlated well with the spontaneous incidence of mammary adenocarcinomas in different murine strains but not with type C MuLV p30 antigen expression. Levels of MMTV gp52, the major type-B viral glycoprotein, corresponded to p14 levels, suggesting that their control is comparably regulated. Evidence that this low m.w. polypeptide is present in feral and inbred strains of widely differing geographic origin and in MMTV with apparently different biologic properties suggests surprising conservation of MMTV protein homology."} {"id": "PMID:168264", "title": "Analysis of sera from SV40-immunized and tumor-bearing hosts for blocking activity and antibody-dependent cellular cytotoxicity.", "content": "The role of serum factors in tumor immunity to cells transformed by PARA-(defective SV40)-adenovirus 7 was investigated. It was found that sera from SV40-sensitized hosts did not block the specific cytotoxicity of SV40-sensitized spleen cells for PARA-7 cells. However, such sera could collaborate with nonsensitized spleen cells to produce specific killing. This activity could be absorbed out by PARA-7 cells but not by cells transformed by cytomegalovirus. The activity of sera from hamsters bearing tumor isografts depended upon when, after transplantation, the specimens were obtained. Sera collected greater than or equal to 10 days after grafting completely blocked immune spleen cell cytotoxicity and did not mediate target cell killing in the presence of normal spleen cells. Sera obtained at an earlier time, i.e., 3 to 6 days after transplantation, consistently were active in the antibody-dependent cellular cytotoxicity test and exhibited reduced or no blocking of antibody-independent cellular cytotoxicity. Thus, there appears to be an inverse correlation in the capacity of serum from tumor bearing hosts to block effector cell cytotoxicity and mediate antibody-dependent cellular cytotoxicity.", "contents": "Analysis of sera from SV40-immunized and tumor-bearing hosts for blocking activity and antibody-dependent cellular cytotoxicity. The role of serum factors in tumor immunity to cells transformed by PARA-(defective SV40)-adenovirus 7 was investigated. It was found that sera from SV40-sensitized hosts did not block the specific cytotoxicity of SV40-sensitized spleen cells for PARA-7 cells. However, such sera could collaborate with nonsensitized spleen cells to produce specific killing. This activity could be absorbed out by PARA-7 cells but not by cells transformed by cytomegalovirus. The activity of sera from hamsters bearing tumor isografts depended upon when, after transplantation, the specimens were obtained. Sera collected greater than or equal to 10 days after grafting completely blocked immune spleen cell cytotoxicity and did not mediate target cell killing in the presence of normal spleen cells. Sera obtained at an earlier time, i.e., 3 to 6 days after transplantation, consistently were active in the antibody-dependent cellular cytotoxicity test and exhibited reduced or no blocking of antibody-independent cellular cytotoxicity. Thus, there appears to be an inverse correlation in the capacity of serum from tumor bearing hosts to block effector cell cytotoxicity and mediate antibody-dependent cellular cytotoxicity."} {"id": "PMID:168265", "title": "Immunologic effects of neonatal infection with mouse thymic virus.", "content": "Mouse thymic virus is a herpesvirus that causes extensive thymic necrosis when given to newborn mice. During the time of acute infection spleen cells have markedly diminished reactivity to T cell phytomitogens and to allogeneic cells and are incapable of effecting a primary in vitro response to a \"T-dependent\" antigen; responses to B cell mitogens and to a T-independent antigen are unimpaired. Spleens from acutely infected mice have low theta antigen normal numbers of immunoglobulin-bearing cells. Surprisingly, despite widespread necrosis and cellular depletion, thymic cell reactivity to mitogens is unimpaired. However, the ability to thymocytes to proliferate and to generate cytotoxic killer cells in response to allogeneic cells is diminished.", "contents": "Immunologic effects of neonatal infection with mouse thymic virus. Mouse thymic virus is a herpesvirus that causes extensive thymic necrosis when given to newborn mice. During the time of acute infection spleen cells have markedly diminished reactivity to T cell phytomitogens and to allogeneic cells and are incapable of effecting a primary in vitro response to a \"T-dependent\" antigen; responses to B cell mitogens and to a T-independent antigen are unimpaired. Spleens from acutely infected mice have low theta antigen normal numbers of immunoglobulin-bearing cells. Surprisingly, despite widespread necrosis and cellular depletion, thymic cell reactivity to mitogens is unimpaired. However, the ability to thymocytes to proliferate and to generate cytotoxic killer cells in response to allogeneic cells is diminished."} {"id": "PMID:168266", "title": "The identification of HL-A antigens on fresh and cultured human endothelial cells.", "content": "Human endothelial cells were obtained from the umbilical cord veins of 16 newborns by methods previously described and tested for HL-A antigens by a microcytotoxicity method. HL-A antigens were present on all endothelial cell lines tested. When the HL-A phenotypes of fresh endothelial cells and autologous fetal lymphocytes were compared, a concordance of 70% was observed. When the HL-A phenotypes of maternal lymphocytes and fresh endothelial cells were compared, a maternal contribution to the endothelial cell phenotype was evident in 72% of the possible commmon antigens. Some HL-A antigens were deleted from 11 of 16 endothelial cell lines that were re-typed after 2 weeks in tissue culture. The majority (90%) of deleted antigens were from the second HL-A locus. When three lines of endothelials cells were again re-typed after 6 weeks in culture, no further changes in antigenicity were noted. These findings: a) demonstrate that HL-A antigens are present on human endothelium and suggest that endothelial cells are actively involved in establishing the immunogenicity of a graft, and b) demonstrate that the HL-A antigens on human endothelial cells may be modulated by in vitro culture.", "contents": "The identification of HL-A antigens on fresh and cultured human endothelial cells. Human endothelial cells were obtained from the umbilical cord veins of 16 newborns by methods previously described and tested for HL-A antigens by a microcytotoxicity method. HL-A antigens were present on all endothelial cell lines tested. When the HL-A phenotypes of fresh endothelial cells and autologous fetal lymphocytes were compared, a concordance of 70% was observed. When the HL-A phenotypes of maternal lymphocytes and fresh endothelial cells were compared, a maternal contribution to the endothelial cell phenotype was evident in 72% of the possible commmon antigens. Some HL-A antigens were deleted from 11 of 16 endothelial cell lines that were re-typed after 2 weeks in tissue culture. The majority (90%) of deleted antigens were from the second HL-A locus. When three lines of endothelials cells were again re-typed after 6 weeks in culture, no further changes in antigenicity were noted. These findings: a) demonstrate that HL-A antigens are present on human endothelium and suggest that endothelial cells are actively involved in establishing the immunogenicity of a graft, and b) demonstrate that the HL-A antigens on human endothelial cells may be modulated by in vitro culture."} {"id": "PMID:168267", "title": "Depression of in vitro responsiveness to phytohemagglutinin in spleen cells cultured from chickens with Marek's disease.", "content": "Cultures of dispersed spleen cells, prepared from MDV-infected chickens with MD visceral lymphomas, showed marked depression of responsiveness to the T cell mitogen PHA, as measured by 3H-Tdr incorporation in cells in vitro. When data are expressed quantitatively in terms of cpm/10(5) viable cells, the functional depletion of PHA-responsive cells appear to result from lower levels of 3H-Tdr incorporation in the PHA-stimulated spleen cultures from chickens with acute MD symptoms, as compared to similar cultures from uninfected isolator-reared control chickens. It is suggested that depression of PHA-induced blastogenesis is spleen cell cultures from chickens with acute MD reflects virus-related alterations in T lymphocytes.", "contents": "Depression of in vitro responsiveness to phytohemagglutinin in spleen cells cultured from chickens with Marek's disease. Cultures of dispersed spleen cells, prepared from MDV-infected chickens with MD visceral lymphomas, showed marked depression of responsiveness to the T cell mitogen PHA, as measured by 3H-Tdr incorporation in cells in vitro. When data are expressed quantitatively in terms of cpm/10(5) viable cells, the functional depletion of PHA-responsive cells appear to result from lower levels of 3H-Tdr incorporation in the PHA-stimulated spleen cultures from chickens with acute MD symptoms, as compared to similar cultures from uninfected isolator-reared control chickens. It is suggested that depression of PHA-induced blastogenesis is spleen cell cultures from chickens with acute MD reflects virus-related alterations in T lymphocytes."} {"id": "PMID:168268", "title": "Establishment of replicating long-term lines of rabbit macrophages and lymphocytes.", "content": "Macrophages (monocyte derived) and lymphocytes have been successfully cultured from rabbit peripheral blood so that replicating long-term cultures are maintained both in media and in the viable, frozen state. The macrophages are considered as such on the basis of phagocytic capabilities, gamma-globulin receptor sites as evidenced by rosette formation with sensitized red cells and disparate enzyme content from the lymphocytes.", "contents": "Establishment of replicating long-term lines of rabbit macrophages and lymphocytes. Macrophages (monocyte derived) and lymphocytes have been successfully cultured from rabbit peripheral blood so that replicating long-term cultures are maintained both in media and in the viable, frozen state. The macrophages are considered as such on the basis of phagocytic capabilities, gamma-globulin receptor sites as evidenced by rosette formation with sensitized red cells and disparate enzyme content from the lymphocytes."} {"id": "PMID:168269", "title": "An improved quantitative micro-complement fixation test.", "content": "The technical procedures for a simple quantitative micro-complement (C) fixation test are described. Major advantages of the present technique compared with the previously described method are: a) a simple measurement of the residual hemolytic activity of C by counting the radioactivity released from 51Cr-labeled sensitized sheep erythrocytes (51Cr-EA); b) an increased sensitivity of the test, brought about by the use of a relatively small number of 51CR-EA per reaction volume; and c) an increased specificity of the test, achieved by maintaining a constant amount of C available for the specific antigen--antibody reaction.", "contents": "An improved quantitative micro-complement fixation test. The technical procedures for a simple quantitative micro-complement (C) fixation test are described. Major advantages of the present technique compared with the previously described method are: a) a simple measurement of the residual hemolytic activity of C by counting the radioactivity released from 51Cr-labeled sensitized sheep erythrocytes (51Cr-EA); b) an increased sensitivity of the test, brought about by the use of a relatively small number of 51CR-EA per reaction volume; and c) an increased specificity of the test, achieved by maintaining a constant amount of C available for the specific antigen--antibody reaction."} {"id": "PMID:168272", "title": "The fine structure of developing human epidermis: light, scanning, and transmission electron microscopy of the periderm.", "content": "Eight stages in the development of the human embryonic and fetal periderm have been established, primarily on the basis of surface morphology, major changes in epidermal stratification, and differentiation. The changes in the periderm observed with the scanning electron microscope have been correlated with and supplemented by cytologic studies with the transmission electron microscope in the periderm and other epidermal layers. Light microscopy was used to determine what proportion of the epidermal thickness is accounted for by the periderm and what relationship individual periderm cells have with underlying cells. The results yield a comprehensive, three-dimensional image of the human epidermis during development and support a concept of the periderm as a layer of \"dynamic\" cells which project superficial blebs, expand in surface area, then regress at the onset of keratinization, leaving only cellular remnants associated with the adult type epidermis.", "contents": "The fine structure of developing human epidermis: light, scanning, and transmission electron microscopy of the periderm. Eight stages in the development of the human embryonic and fetal periderm have been established, primarily on the basis of surface morphology, major changes in epidermal stratification, and differentiation. The changes in the periderm observed with the scanning electron microscope have been correlated with and supplemented by cytologic studies with the transmission electron microscope in the periderm and other epidermal layers. Light microscopy was used to determine what proportion of the epidermal thickness is accounted for by the periderm and what relationship individual periderm cells have with underlying cells. The results yield a comprehensive, three-dimensional image of the human epidermis during development and support a concept of the periderm as a layer of \"dynamic\" cells which project superficial blebs, expand in surface area, then regress at the onset of keratinization, leaving only cellular remnants associated with the adult type epidermis."} {"id": "PMID:168273", "title": "Cyclic AMP, cyclic GMP, and glucocorticoids as potential metabolic regulators of epidermal proliferation and differentiation.", "content": "The two cyclic nucleotides, cyclic AMP and cyclic GMP, appear to be central to the metabolic regulation of cell proliferation and differentiation in various cells. Moreover, in many systems glucocorticoids appear to act in concert with or parallel to cyclic AMP. The available evidence suggests that these three molecular species--cyclic AMP, cyclic GMP, and glucocorticoids--may be essential to the normal regulation of epidermal proliferation and differentiation. In 1970, we suggested that perturbed epidermal homeostasis, exemplified by psoriasis, might be associated with low cellular levels of cyclic AMP and, in 1972, with high levels of cyclic GMP as well. Subsequent measurements of these two cyclic nucleotides in our laboratory showed a probable reduction in the cyclic AMP/cyclic GMP ratio in lesional psoriatic tissue. This led to the hypothesis that the cardinal features of psoriatic epidermis--glycogen accumulation, excessive proliferation, and reduced cell specialization--are the results of this reduced ratio. A corollary of this hypothesis was that a psoriatic lesion could not begin or exist without this altered cyclic nucleotide ratio. Recently, four different agents--lithium, a beta adrenergic blocking agent, antimalarials, and iodide--have been found to exacerbate psoriasis and to reduce the formation of cyclic AMP in various tissues. Consequently we believe that cyclic nucleotides are of central importance in the pathogenesis of the epidermal component of psoriasis.", "contents": "Cyclic AMP, cyclic GMP, and glucocorticoids as potential metabolic regulators of epidermal proliferation and differentiation. The two cyclic nucleotides, cyclic AMP and cyclic GMP, appear to be central to the metabolic regulation of cell proliferation and differentiation in various cells. Moreover, in many systems glucocorticoids appear to act in concert with or parallel to cyclic AMP. The available evidence suggests that these three molecular species--cyclic AMP, cyclic GMP, and glucocorticoids--may be essential to the normal regulation of epidermal proliferation and differentiation. In 1970, we suggested that perturbed epidermal homeostasis, exemplified by psoriasis, might be associated with low cellular levels of cyclic AMP and, in 1972, with high levels of cyclic GMP as well. Subsequent measurements of these two cyclic nucleotides in our laboratory showed a probable reduction in the cyclic AMP/cyclic GMP ratio in lesional psoriatic tissue. This led to the hypothesis that the cardinal features of psoriatic epidermis--glycogen accumulation, excessive proliferation, and reduced cell specialization--are the results of this reduced ratio. A corollary of this hypothesis was that a psoriatic lesion could not begin or exist without this altered cyclic nucleotide ratio. Recently, four different agents--lithium, a beta adrenergic blocking agent, antimalarials, and iodide--have been found to exacerbate psoriasis and to reduce the formation of cyclic AMP in various tissues. Consequently we believe that cyclic nucleotides are of central importance in the pathogenesis of the epidermal component of psoriasis."} {"id": "PMID:168275", "title": "In vitro activity of silver sulfadiazine against Herpesvirus hominis.", "content": "Silver sulfadiazine, at a concentration of 10 mug/ml, inhibits Herpesvirus hominis types 1 and 2 in vitro. The antiviral effect is directly related to concentration of the drug and duration of exposure.", "contents": "In vitro activity of silver sulfadiazine against Herpesvirus hominis. Silver sulfadiazine, at a concentration of 10 mug/ml, inhibits Herpesvirus hominis types 1 and 2 in vitro. The antiviral effect is directly related to concentration of the drug and duration of exposure."} {"id": "PMID:168276", "title": "Experimental aminoglycoside nephrotoxicity.", "content": "The nephrotoxicities of gentamicin and three other experimental aminoglycosides were compared at a single 60 mg. per kilogram per day dose in rats. Renal function, lysosomal enzymuria, and antibiotic concentrations in plasma, urine, and renal tissue were measured at regular intervals throughout the course of treatment. Kidney tissue was examined by light and electron microscopy in animals killed at intervals throughout the period of antibiotic administration. Proteinuria and enzymuria were early indicators of nephron dysfunction, whereas endogenous creatinine clearance declined later in the course of treatment. All animals were killed 24 hours after a previous antibiotic injection and displayed sustained renal tissue antibiotic concentrations which were 5 to 10 times higher than those in serum or urine. When assayed separately, renal cortical tissue had a fivefold greater antibiotic concentration than renal medulla. Light microscopy displayed necrosis of the pars convoluta of the proximal tubule. Electron microscopy revealed appearance of cytosegrosomes with myeloid bodies. It is possible that impaired cytoplasmic degradation of sequestered organelle membranes, resulting from aminoglycoside accumulation, is responsible for the myeloid body formation and subsequent tubular necrosis.", "contents": "Experimental aminoglycoside nephrotoxicity. The nephrotoxicities of gentamicin and three other experimental aminoglycosides were compared at a single 60 mg. per kilogram per day dose in rats. Renal function, lysosomal enzymuria, and antibiotic concentrations in plasma, urine, and renal tissue were measured at regular intervals throughout the course of treatment. Kidney tissue was examined by light and electron microscopy in animals killed at intervals throughout the period of antibiotic administration. Proteinuria and enzymuria were early indicators of nephron dysfunction, whereas endogenous creatinine clearance declined later in the course of treatment. All animals were killed 24 hours after a previous antibiotic injection and displayed sustained renal tissue antibiotic concentrations which were 5 to 10 times higher than those in serum or urine. When assayed separately, renal cortical tissue had a fivefold greater antibiotic concentration than renal medulla. Light microscopy displayed necrosis of the pars convoluta of the proximal tubule. Electron microscopy revealed appearance of cytosegrosomes with myeloid bodies. It is possible that impaired cytoplasmic degradation of sequestered organelle membranes, resulting from aminoglycoside accumulation, is responsible for the myeloid body formation and subsequent tubular necrosis."} {"id": "PMID:168277", "title": "The spectrum of electrophoretic mobility of very low density lipoproteins: role of slower migrating species in endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) and broad-beta disease (type III).", "content": "To test whether beta-migrating very low-density lipoproteins (VLDL, d less than 1.006) might not be unique to broad-beta disease (with a Type III lipoprotein pattern) but rather a caricature of an intermediate species in the catabolism of triglyceride-rich lipoproteins of normal composition and electrophoretic mobility in nonretarding media, VLDL from subjects with endogenous hypertriglyceridemia (with a Type IV pattern) or broad-beta disease were analyzed under varying dietary and pharmacologic conditions following starch-block electrophoresis. These studies revealed a spectrum in electrophoretic mobility and lipid composition throughout the Sf20 to 400 range: the more buoyant, triglyceride-rich VLDL migrated faster and the denser, triglyceride-poor VLDL more slowly, but the VLDL were broadly and continuously distributed throughout the entire beta to alpha2 regions in both disorders. However, in each subfraction of VLDL (Sf100 to 400, 60 to 100 and 20 to 60) as well as in the whole Sf20 to 400 class, the relative proportion of slower species was greater in the subjects with broad-beta disease than in those with endogenous hypertriglyceridemia. Under conditions of acutely stimulated VLDL production (following an oral fat load), a late increase in the slower species was observed as alimentary lipemia resolved. During chronic VLDL hypersecretion (with high carbohydrate feeding) both faster and slower species increased in a subject with broad-beta disease. In the same subject during clofibrate therapy, the faster species were decreased more than the slower on both normal and high carbohydrate diets. Acute acceleration of VLDL catabolism by heparin administration increased the slower VLDL at the expense of the faster, both in this subject and in a counterpart with endogenous hypertriglyceridemia. These studies are consistent with the hypothesis that slower migrating, triglyceride-poor VLDL are normal intermediate (or remnant) forms in a continuous catabolic process. The concentration of these remnants is dwarfed by that of the faster species in subjects with endogenous hypertriglyceridemia. However, in subjects with broad-beta disease they accumulate as the beta-VLDL characteristic of this disorder, most likely as a result of a relative blockade in their further catabolism.", "contents": "The spectrum of electrophoretic mobility of very low density lipoproteins: role of slower migrating species in endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) and broad-beta disease (type III). To test whether beta-migrating very low-density lipoproteins (VLDL, d less than 1.006) might not be unique to broad-beta disease (with a Type III lipoprotein pattern) but rather a caricature of an intermediate species in the catabolism of triglyceride-rich lipoproteins of normal composition and electrophoretic mobility in nonretarding media, VLDL from subjects with endogenous hypertriglyceridemia (with a Type IV pattern) or broad-beta disease were analyzed under varying dietary and pharmacologic conditions following starch-block electrophoresis. These studies revealed a spectrum in electrophoretic mobility and lipid composition throughout the Sf20 to 400 range: the more buoyant, triglyceride-rich VLDL migrated faster and the denser, triglyceride-poor VLDL more slowly, but the VLDL were broadly and continuously distributed throughout the entire beta to alpha2 regions in both disorders. However, in each subfraction of VLDL (Sf100 to 400, 60 to 100 and 20 to 60) as well as in the whole Sf20 to 400 class, the relative proportion of slower species was greater in the subjects with broad-beta disease than in those with endogenous hypertriglyceridemia. Under conditions of acutely stimulated VLDL production (following an oral fat load), a late increase in the slower species was observed as alimentary lipemia resolved. During chronic VLDL hypersecretion (with high carbohydrate feeding) both faster and slower species increased in a subject with broad-beta disease. In the same subject during clofibrate therapy, the faster species were decreased more than the slower on both normal and high carbohydrate diets. Acute acceleration of VLDL catabolism by heparin administration increased the slower VLDL at the expense of the faster, both in this subject and in a counterpart with endogenous hypertriglyceridemia. These studies are consistent with the hypothesis that slower migrating, triglyceride-poor VLDL are normal intermediate (or remnant) forms in a continuous catabolic process. The concentration of these remnants is dwarfed by that of the faster species in subjects with endogenous hypertriglyceridemia. However, in subjects with broad-beta disease they accumulate as the beta-VLDL characteristic of this disorder, most likely as a result of a relative blockade in their further catabolism."} {"id": "PMID:168278", "title": "Role of insulin and glucose in the induction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients.", "content": "It is generally assumed, but not established, that the lowering of plasma free amino acid levels following glucose intake is entirely mediated by stimulated insulin secretion. This problem was investigated in groups of healthy volunteer subjects, juvenile diabetics, and insuloma patients. The plasma concentrations of 15 individual free amino acids, glucose, and insulin or C-peptide were determined before and at intervals after either oral glucose (75 Gm.) or intravenous glucose (0.25 Gm. per kilogram of body weight) or tolbutamide (1 Gm.). Glucose lowered plasma amino acid levels in both situations of stimulated (healthy volunteer subjects) and absent (diabetic) insulin secretion. The lack of insulin response in juvenile diabetics was evident by the lack of any significant increase in C-peptide levels following glucose ingestion. Nevertheless, despite markedly greater plasma glucose levels, hypoaminoacidemia was less severe in diabetics than in normal volunteer subjects. In comparison to healthy volunteer subjects who showed significant decreases in concentrations of 14 of 15 examined amino acids by glucose, the diabetic individuals exhibited significant decreases in concentration of 8 amino acids (leucine, isoleucine, valine, tyrosine, phenylalanine, methionine, citrulline, and arginine). In face of a massively greater insulin response in an insuloma patient (greater than 1,000 muU per milliliter), the decreases in the levels of individual free amino acids following glucose were within the range of values obtained in the normal volunteer subjects. The stimulation of insulin secretion with tolbutamide also lowered the concentrations of free amino acids in plasma. However, one importnat difference distinguished the effect of tolbutamide from that of glucose. Within a few minutes after the injection of tolbutamide, there was a marked and persistent fall in alanine levels, while during the entire course of the glucose tolerance test there were no significant changes in the level of this amino acid, suggesting a difference in the mechanism of hypoaminoacidemia induced by endogenous insulin in the presence or absence of exogenous glucose. Despite a markedly greater insulin response to tolbutamide in the insuloma patient (greater than 1,500 muU per milliliter), the decreases in plasma glucose and free amino acid levels fell within the range of values obtained in normal volunteer subjects. In conclusion, the exogenous glucose per se lowers the levels of free amino acids in plasma. This effect is enhanced by insulin.", "contents": "Role of insulin and glucose in the induction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients. It is generally assumed, but not established, that the lowering of plasma free amino acid levels following glucose intake is entirely mediated by stimulated insulin secretion. This problem was investigated in groups of healthy volunteer subjects, juvenile diabetics, and insuloma patients. The plasma concentrations of 15 individual free amino acids, glucose, and insulin or C-peptide were determined before and at intervals after either oral glucose (75 Gm.) or intravenous glucose (0.25 Gm. per kilogram of body weight) or tolbutamide (1 Gm.). Glucose lowered plasma amino acid levels in both situations of stimulated (healthy volunteer subjects) and absent (diabetic) insulin secretion. The lack of insulin response in juvenile diabetics was evident by the lack of any significant increase in C-peptide levels following glucose ingestion. Nevertheless, despite markedly greater plasma glucose levels, hypoaminoacidemia was less severe in diabetics than in normal volunteer subjects. In comparison to healthy volunteer subjects who showed significant decreases in concentrations of 14 of 15 examined amino acids by glucose, the diabetic individuals exhibited significant decreases in concentration of 8 amino acids (leucine, isoleucine, valine, tyrosine, phenylalanine, methionine, citrulline, and arginine). In face of a massively greater insulin response in an insuloma patient (greater than 1,000 muU per milliliter), the decreases in the levels of individual free amino acids following glucose were within the range of values obtained in the normal volunteer subjects. The stimulation of insulin secretion with tolbutamide also lowered the concentrations of free amino acids in plasma. However, one importnat difference distinguished the effect of tolbutamide from that of glucose. Within a few minutes after the injection of tolbutamide, there was a marked and persistent fall in alanine levels, while during the entire course of the glucose tolerance test there were no significant changes in the level of this amino acid, suggesting a difference in the mechanism of hypoaminoacidemia induced by endogenous insulin in the presence or absence of exogenous glucose. Despite a markedly greater insulin response to tolbutamide in the insuloma patient (greater than 1,500 muU per milliliter), the decreases in plasma glucose and free amino acid levels fell within the range of values obtained in normal volunteer subjects. In conclusion, the exogenous glucose per se lowers the levels of free amino acids in plasma. This effect is enhanced by insulin."} {"id": "PMID:168279", "title": "Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic-adenosine monophosphate during prolonged administration.", "content": "Lithium (Li+) chloride, 2 to 3 mEq. per kilogram of body weight, was administered intraperitoneally to normal Wistar rats daily for 4 to 66 days. This resulted in a marked reduction in urine osmolality (Uosm.) and increase in the excretion of water, Na+, K+, uric acid, and phosphate. The excretion of uric acid and potassium was a direct function of UNaV. The magnitude of depression in urine osmolality was significantly related to the rate of excretion of lithium in the urine, suggesting that the change in water reabsorption is dependent on the presence of the ion in the luminal side of the tubule. During 2 per cent saline diuresis, Li+-treated rats achieved less fractional free water reabsorption (TcH2O/GFR times 100) at any level of fractional osmolar clearance (Cosm./GFR times 100) than normal rats. On the other hand, during 0.225 per cent saline diuresis, fractional free water clearance (CH2O/GFR times 100) was normal over a wide range of fractional urine flow (V/GFR times 100), indicating intact function of the ascending limb of the loop of Henle. The intravenous infusion of vasopressin (VP) or dibutyryl cyclic-adenosine monophosphate (dcAMP) to Li+-treated rats resulted in a modest rise in Uosm. and a reduction in V/GFR times 100 and CH2O/GFR times 100. Although the response to VP appeared earlier than that to dibutyryl cyclic-AMP, the magnitude of the changes in Uosm., V/GFR times 100, and CH2O/GFR times 100 was eventually the same with both substances. Comparison between normal and Li+-treated rats revealed that the response to both VP and dibutyryl cyclic-AMP was blunted, albeit to a greater extent in the former. Inhibition by Li+ of adenylate cyclase will only partially explain the present data. Impairment in the release of endogenous VP or a block distal to the formation of cyclic-AMP must have played a role. In view of a normal diluting capacity and the increase in the excretion of phosphate and uric acid, it is suggested that Li+, when administered chronically in the present doses, inhibits proximal tubular reabsorption.", "contents": "Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic-adenosine monophosphate during prolonged administration. Lithium (Li+) chloride, 2 to 3 mEq. per kilogram of body weight, was administered intraperitoneally to normal Wistar rats daily for 4 to 66 days. This resulted in a marked reduction in urine osmolality (Uosm.) and increase in the excretion of water, Na+, K+, uric acid, and phosphate. The excretion of uric acid and potassium was a direct function of UNaV. The magnitude of depression in urine osmolality was significantly related to the rate of excretion of lithium in the urine, suggesting that the change in water reabsorption is dependent on the presence of the ion in the luminal side of the tubule. During 2 per cent saline diuresis, Li+-treated rats achieved less fractional free water reabsorption (TcH2O/GFR times 100) at any level of fractional osmolar clearance (Cosm./GFR times 100) than normal rats. On the other hand, during 0.225 per cent saline diuresis, fractional free water clearance (CH2O/GFR times 100) was normal over a wide range of fractional urine flow (V/GFR times 100), indicating intact function of the ascending limb of the loop of Henle. The intravenous infusion of vasopressin (VP) or dibutyryl cyclic-adenosine monophosphate (dcAMP) to Li+-treated rats resulted in a modest rise in Uosm. and a reduction in V/GFR times 100 and CH2O/GFR times 100. Although the response to VP appeared earlier than that to dibutyryl cyclic-AMP, the magnitude of the changes in Uosm., V/GFR times 100, and CH2O/GFR times 100 was eventually the same with both substances. Comparison between normal and Li+-treated rats revealed that the response to both VP and dibutyryl cyclic-AMP was blunted, albeit to a greater extent in the former. Inhibition by Li+ of adenylate cyclase will only partially explain the present data. Impairment in the release of endogenous VP or a block distal to the formation of cyclic-AMP must have played a role. In view of a normal diluting capacity and the increase in the excretion of phosphate and uric acid, it is suggested that Li+, when administered chronically in the present doses, inhibits proximal tubular reabsorption."} {"id": "PMID:168280", "title": "Lymphocyte-associated antigens in patients with alveolar cell carcinoma.", "content": "Antiserum produced in rabbits against a virus-like particle pellet recovered from human alveolar cell carcinoma (ACC) was used for the detection of lymphocyte-associated antigen in patients with ACC. The method used was direct immunofluorescence. The results demonstrate that lymphocytes from some patients with ACC possess antigen and the presence of lymphocyte fluorescence in patients with ACC suggests widespread or metastatic disease. The presence of antigen may be of both diagnostic and prognostic value.", "contents": "Lymphocyte-associated antigens in patients with alveolar cell carcinoma. Antiserum produced in rabbits against a virus-like particle pellet recovered from human alveolar cell carcinoma (ACC) was used for the detection of lymphocyte-associated antigen in patients with ACC. The method used was direct immunofluorescence. The results demonstrate that lymphocytes from some patients with ACC possess antigen and the presence of lymphocyte fluorescence in patients with ACC suggests widespread or metastatic disease. The presence of antigen may be of both diagnostic and prognostic value."} {"id": "PMID:168281", "title": "Measurement of unsaturated \"\"granulocyte-related'' (TC I and TC III) and \"\"liver-related'' (TC II) B12 binders by instant batch separation using a microfine precipitate of silica (QUSO G32).", "content": "A microfine precipitate of silica (Quso G32) almost instantly quantitatively adsorbs the polypeptide transcobalamin II from serum without adsorbing the glycoproteins transcobalamins I and III. This provides a simple, rapid, and reproducible method for the measurement of the granulocyte-related transcobalamins I and III and the liver-related transcobalamin II in serum, and is also applicable to their purification, and the separation and purification of other polypeptide-glycoprotein mixtures.", "contents": "Measurement of unsaturated \"\"granulocyte-related'' (TC I and TC III) and \"\"liver-related'' (TC II) B12 binders by instant batch separation using a microfine precipitate of silica (QUSO G32). A microfine precipitate of silica (Quso G32) almost instantly quantitatively adsorbs the polypeptide transcobalamin II from serum without adsorbing the glycoproteins transcobalamins I and III. This provides a simple, rapid, and reproducible method for the measurement of the granulocyte-related transcobalamins I and III and the liver-related transcobalamin II in serum, and is also applicable to their purification, and the separation and purification of other polypeptide-glycoprotein mixtures."} {"id": "PMID:168282", "title": "Extranasopharyngeal juvenile angiofibroma.", "content": "A rare case of juvenile angiofibroma arising from the base of the skull outside the nasopharynx and extending into the pterygo-maxillary fossa and cheek is discribed. It is possible, by a combined zygomatic and buccal approach, successfully to excise such a tumour.", "contents": "Extranasopharyngeal juvenile angiofibroma. A rare case of juvenile angiofibroma arising from the base of the skull outside the nasopharynx and extending into the pterygo-maxillary fossa and cheek is discribed. It is possible, by a combined zygomatic and buccal approach, successfully to excise such a tumour."} {"id": "PMID:168283", "title": "Uptake of 125-I-labelled human placental lactogen and human placental lactogen by the tissues of normal and lactating rats.", "content": "The rate of clearance from the circulation and uptake into tissues of radioactive label was studied after i.v. injection of 125-I-labelled human placental lactogen (HPL) into rats at various stages of pregnancy. The half-life was obtained for the disappearance of the trichloroacetic acid-precipitable material from the plasma. The half-life, t1/2(S), calculated over the first 5 min after injection of the hormone was 5.4 equals or minus 1.1 (S.D.) min, while a half-life, t1/2(L), of 27.9 equals or minus 2.3 min was obtained from the decay period of 15-35 min. In the non-pregnant and pregnant rat the highest ratio of the radioactivity in an organ to that in the blood was 12-14:1 in the kidney. That the kidney is mainly involved in the uptake of exogenous HPL is further confirmed by the application of the histochemical immunoperoxidase technique. Human placental lactogen was localized in the cells of the proximal tubules of the cortex and to a lesser extent in the tubular lumen and the tubules of the medulla region. UPTAKE OF HPL in vivo occurs in the mammary gland tissue of the post-partum rat and reaches a maximum uptake between 15 and 30 min after injection of the hormone. Furthermore, specific uptake of HPL was observed on the alveolar cell membranes after the incubation of paraffin-embedded sections of formalin-fixed mammary gland and subsequent treatment by the peroxidase-labelled antibody method. These findings support the work of others who have demonstrated the presence of specific membrane receptors in the mammary gland for hormones with prolactin-like activity.", "contents": "Uptake of 125-I-labelled human placental lactogen and human placental lactogen by the tissues of normal and lactating rats. The rate of clearance from the circulation and uptake into tissues of radioactive label was studied after i.v. injection of 125-I-labelled human placental lactogen (HPL) into rats at various stages of pregnancy. The half-life was obtained for the disappearance of the trichloroacetic acid-precipitable material from the plasma. The half-life, t1/2(S), calculated over the first 5 min after injection of the hormone was 5.4 equals or minus 1.1 (S.D.) min, while a half-life, t1/2(L), of 27.9 equals or minus 2.3 min was obtained from the decay period of 15-35 min. In the non-pregnant and pregnant rat the highest ratio of the radioactivity in an organ to that in the blood was 12-14:1 in the kidney. That the kidney is mainly involved in the uptake of exogenous HPL is further confirmed by the application of the histochemical immunoperoxidase technique. Human placental lactogen was localized in the cells of the proximal tubules of the cortex and to a lesser extent in the tubular lumen and the tubules of the medulla region. UPTAKE OF HPL in vivo occurs in the mammary gland tissue of the post-partum rat and reaches a maximum uptake between 15 and 30 min after injection of the hormone. Furthermore, specific uptake of HPL was observed on the alveolar cell membranes after the incubation of paraffin-embedded sections of formalin-fixed mammary gland and subsequent treatment by the peroxidase-labelled antibody method. These findings support the work of others who have demonstrated the presence of specific membrane receptors in the mammary gland for hormones with prolactin-like activity."} {"id": "PMID:168284", "title": "Oestradiol-induced synthesis of a specific uterine protein in propranolol-treated rats.", "content": "While there is conflicting evidence concerning an effect of oestradiol on uterine cyclic AMP concentration, results from different laboratories (including ours) are in agreement that even when observed, the early increase in uterine cyclic AMP after oestradiol injection fails to occur when propranolol, a beta-adrenergic blocking agent, is given (50 mug, i.p.) 20 min before the oestradiol. The present work shows that pretreatment with propranolol failed to inhibit an early uterine response to oestradiol, namely the synthesis after 1 h of uterine protein, or class of proteins, IP. It is concluded that the induction of IP by oestradiol does not depend on an increase in uterine cyclic AMP concentration and that beta-adrenergic receptors do not have a role in this oestrogenic response.", "contents": "Oestradiol-induced synthesis of a specific uterine protein in propranolol-treated rats. While there is conflicting evidence concerning an effect of oestradiol on uterine cyclic AMP concentration, results from different laboratories (including ours) are in agreement that even when observed, the early increase in uterine cyclic AMP after oestradiol injection fails to occur when propranolol, a beta-adrenergic blocking agent, is given (50 mug, i.p.) 20 min before the oestradiol. The present work shows that pretreatment with propranolol failed to inhibit an early uterine response to oestradiol, namely the synthesis after 1 h of uterine protein, or class of proteins, IP. It is concluded that the induction of IP by oestradiol does not depend on an increase in uterine cyclic AMP concentration and that beta-adrenergic receptors do not have a role in this oestrogenic response."} {"id": "PMID:168285", "title": "Synthesis and secretion of a large glycoprotein in the pars intermedia.", "content": "The biosynthesis, intracellular transport and release of [3-H]-leucine-containing secretory product has been followed in the pars intermedia of Xenopus laevis and, in particular, the synthesis and secretion of a large molecular weight glycoprotein secretory product was demonstrated. However, if Xenopus adrenocorticotrophin does contain a leucine residue the results obtained provided no support for the view that it serves as a precursor for melanocytestimulating hormone in this species.", "contents": "Synthesis and secretion of a large glycoprotein in the pars intermedia. The biosynthesis, intracellular transport and release of [3-H]-leucine-containing secretory product has been followed in the pars intermedia of Xenopus laevis and, in particular, the synthesis and secretion of a large molecular weight glycoprotein secretory product was demonstrated. However, if Xenopus adrenocorticotrophin does contain a leucine residue the results obtained provided no support for the view that it serves as a precursor for melanocytestimulating hormone in this species."} {"id": "PMID:168295", "title": "Aspects of the adrenal function in the domestic fowl.", "content": "Chromatographic purification of extracts of hen peripheral plasma on Florisil columns before measurement by spectrofluorometry showed a basal level for corticosterone of 1-3 mug/100 ml, which is much lower than concentrations previously reported using acid fluorescence. Neither handling, restraint nor repeated bleeding affected the concentration of this hormone or of glucose. Adrenal function tests with two preparations of synthetic corticotrophin showed that they caused a rapid rise in blood corticosterone and eventually of glucose. Results of studies using insulin or tolbutamide i.v. suggest that there is a threshold concentration of plasma glucose (about 70 mg/100 ml) below which hypoglycaemia stimulates the hypothalamic-pituitary-adrenal system in fowls. Prolonged treatment of laying hens with protamine zinc insulin led to aphagia and cessation of egg-laying; increased concentrations of corticosterone were observed 2 days after the administration of insulin ceased, coinciding with the return to normal plasma levels of glucose. 'Chemical adrenalectomy' with metyrapone showed that the restoration of plasma glucose to a normal concentration after insulin treatment is dependent upon fully functional adrenal cortical tissue. It appears likely that the adrenal medulla is a target for corticosterone which probably regulates the tissue levels of phenylethanolamine-N-methyltransferase, one of the enzymes necessary for the biosynthesis of adrenaline.", "contents": "Aspects of the adrenal function in the domestic fowl. Chromatographic purification of extracts of hen peripheral plasma on Florisil columns before measurement by spectrofluorometry showed a basal level for corticosterone of 1-3 mug/100 ml, which is much lower than concentrations previously reported using acid fluorescence. Neither handling, restraint nor repeated bleeding affected the concentration of this hormone or of glucose. Adrenal function tests with two preparations of synthetic corticotrophin showed that they caused a rapid rise in blood corticosterone and eventually of glucose. Results of studies using insulin or tolbutamide i.v. suggest that there is a threshold concentration of plasma glucose (about 70 mg/100 ml) below which hypoglycaemia stimulates the hypothalamic-pituitary-adrenal system in fowls. Prolonged treatment of laying hens with protamine zinc insulin led to aphagia and cessation of egg-laying; increased concentrations of corticosterone were observed 2 days after the administration of insulin ceased, coinciding with the return to normal plasma levels of glucose. 'Chemical adrenalectomy' with metyrapone showed that the restoration of plasma glucose to a normal concentration after insulin treatment is dependent upon fully functional adrenal cortical tissue. It appears likely that the adrenal medulla is a target for corticosterone which probably regulates the tissue levels of phenylethanolamine-N-methyltransferase, one of the enzymes necessary for the biosynthesis of adrenaline."} {"id": "PMID:168297", "title": "A radioimmunoassay for plasma arginine-vasopressin in man and dog: application to physiological and pathological states.", "content": "A radioimmunoassay has been developed for plasma arginine-vasopressin in man and dog. The mean recovery of added arginine-vasopressin (AVP) was 60 +/-6.9 (S.D.)% and the lower threshold of detection 2.0 pmol/1. A close correlation was found between concurrent radioimmunoassay and bioassay values. The mean concentration found in peripheral venous blood in healthy men after overnight fasting was 5.3 pmol/1 (range 4.6-6.2 pmol/1.) In man, significant increases in plasma AVP occurred after dehydration (5-9-9-5 pmol/1) and significant decreases after oral water-loading (5.9-9.5 pmol/1). During i.v. infusion of graded doses of synthetic AVP in normal men, plasma levels were closely correlated with infusion rate. On stopping the infusion, plasma vasopressin fell exponentially with a half-life of between 7 and 8 min. In man, plasma AVP was unaffected by tilting head-up for 2 h, or by a non-hypotensive bleeding of 500 ml in 10 min. In the dog, haemorrhage of 5 ml/kg and over caused proportionate increases in AVP in the circulation. In normal men, plasma vasopressin was significantly correlated with concurrent urinary osmolality. Five patients with oat-cell bronchial carcinoma and hyponatraemia showed a marked increase of plasma vasopressin. Five patients with diabetes insipidus had significantly reduced, but detectable, levels of plasma AVP. The plasma concentration in these patients did not increase after water restriction.", "contents": "A radioimmunoassay for plasma arginine-vasopressin in man and dog: application to physiological and pathological states. A radioimmunoassay has been developed for plasma arginine-vasopressin in man and dog. The mean recovery of added arginine-vasopressin (AVP) was 60 +/-6.9 (S.D.)% and the lower threshold of detection 2.0 pmol/1. A close correlation was found between concurrent radioimmunoassay and bioassay values. The mean concentration found in peripheral venous blood in healthy men after overnight fasting was 5.3 pmol/1 (range 4.6-6.2 pmol/1.) In man, significant increases in plasma AVP occurred after dehydration (5-9-9-5 pmol/1) and significant decreases after oral water-loading (5.9-9.5 pmol/1). During i.v. infusion of graded doses of synthetic AVP in normal men, plasma levels were closely correlated with infusion rate. On stopping the infusion, plasma vasopressin fell exponentially with a half-life of between 7 and 8 min. In man, plasma AVP was unaffected by tilting head-up for 2 h, or by a non-hypotensive bleeding of 500 ml in 10 min. In the dog, haemorrhage of 5 ml/kg and over caused proportionate increases in AVP in the circulation. In normal men, plasma vasopressin was significantly correlated with concurrent urinary osmolality. Five patients with oat-cell bronchial carcinoma and hyponatraemia showed a marked increase of plasma vasopressin. Five patients with diabetes insipidus had significantly reduced, but detectable, levels of plasma AVP. The plasma concentration in these patients did not increase after water restriction."} {"id": "PMID:168303", "title": "The tip of the Dictyostelium discoideum pseudoplasmodium as an organizer.", "content": "We have extended Raper's original work on the organizing ability of the tip of the Dictyostelium discoideum slug. Our new results are that tips from all multicellular (pseudoplasmodial) stages act as organizers; that the structure organized by a tip depends on the developmental stage of the cells responding to the tip's signal; that tips from all stages release a qualitatively similar signal which is continuous, most probably a gradient of c-AMP; and that the signal from fruiting-body tips appears stronger than that from conus tips. We discuss these results with reference to the control of morphogenetic movement and patterned differentiation and point out that the D. discoideum tip is analagous to a classical organizer, whose signal is interpreted according to the state of determination of cells in its field of influence.", "contents": "The tip of the Dictyostelium discoideum pseudoplasmodium as an organizer. We have extended Raper's original work on the organizing ability of the tip of the Dictyostelium discoideum slug. Our new results are that tips from all multicellular (pseudoplasmodial) stages act as organizers; that the structure organized by a tip depends on the developmental stage of the cells responding to the tip's signal; that tips from all stages release a qualitatively similar signal which is continuous, most probably a gradient of c-AMP; and that the signal from fruiting-body tips appears stronger than that from conus tips. We discuss these results with reference to the control of morphogenetic movement and patterned differentiation and point out that the D. discoideum tip is analagous to a classical organizer, whose signal is interpreted according to the state of determination of cells in its field of influence."} {"id": "PMID:168304", "title": "Monosynaptic connexions between wing stretch receptors and flight motoneurones of the locust.", "content": "1. The connexions between stretch receptors of the wings and motoneurones innervating flight muscles have been studied anatomically and physiologically. 2. Filling with cobaltous chloride shows that the single neurone of a forewing stretch receptor has a complex pattern of branches within the mesothoracic ganglion and branches which extend into the pro- and meta-thoracic ganglia. The single neurone of a hindwing stretch receptor has extensive branches in the metathoracic ganglion and branches in themesothoracic ganglion. The branches of both receptors are confined to the ipsilateral halves of the ganglia. 3. A stretch receptor gives information about the velocity and extent of elevation of a wing. 4. Each spike of a forewing stretch receptor casuses an EPSP in ipsilateral mesothoracic depressor motoneurones and an IPSP in elevators. The connexions are thought to be monosynaptic for the following reasons. The EPSPs in the first basalar (depressor) motoneurone follow each spike of the stretch receptor at a frequency of 125 Hz and with a constant latency of about 1 msec. In a Ringer solution containing 20 mM-Mg2+ the amplitude EPSP declines gradually. The IPSP'S upon elevators have similar properties but occur with a latency of 4-6 msec. 5. The connexions therefore comprise a monosynaptic negative feed-back loop; elevation of the wing excites the stretch receptor which then inhibits the elevator motoneurones and excites the depressors. 6. A hindwing stretch receptor synapses upon metathoracic flight motoneurones in the same way, causing EPSPs in depressor and IPSPs in elevator motoneurones. 7. No connexions of either fore- or hindwing stretch receptors have been found with contralateral flight motoneurones. 8. Interganglionic connexions are made by both receptors. For example, both fore- and hindwing stretch receptors cause EPSPs upon the meso- and metathoracic first basalar motoneurones. 9. Stimulation of the axon of a stretch receptor with groups of three stimuli repeated every 50-100 msec thus simulating the pattern which it shows during flight, causes subthreshold waves of depolarization in depressor motoneurones. When summed with an unpatterned input, the stretch receptor is able to influence the production of spikes in motoneurones on each cycle. During flight, it is expected that the stretch receptor will influence the time at which a motoneurone will spike and hence have an effect on the amplitude of the upstroke and upon the phase relationship between spikes of motoneurones.", "contents": "Monosynaptic connexions between wing stretch receptors and flight motoneurones of the locust. 1. The connexions between stretch receptors of the wings and motoneurones innervating flight muscles have been studied anatomically and physiologically. 2. Filling with cobaltous chloride shows that the single neurone of a forewing stretch receptor has a complex pattern of branches within the mesothoracic ganglion and branches which extend into the pro- and meta-thoracic ganglia. The single neurone of a hindwing stretch receptor has extensive branches in the metathoracic ganglion and branches in themesothoracic ganglion. The branches of both receptors are confined to the ipsilateral halves of the ganglia. 3. A stretch receptor gives information about the velocity and extent of elevation of a wing. 4. Each spike of a forewing stretch receptor casuses an EPSP in ipsilateral mesothoracic depressor motoneurones and an IPSP in elevators. The connexions are thought to be monosynaptic for the following reasons. The EPSPs in the first basalar (depressor) motoneurone follow each spike of the stretch receptor at a frequency of 125 Hz and with a constant latency of about 1 msec. In a Ringer solution containing 20 mM-Mg2+ the amplitude EPSP declines gradually. The IPSP'S upon elevators have similar properties but occur with a latency of 4-6 msec. 5. The connexions therefore comprise a monosynaptic negative feed-back loop; elevation of the wing excites the stretch receptor which then inhibits the elevator motoneurones and excites the depressors. 6. A hindwing stretch receptor synapses upon metathoracic flight motoneurones in the same way, causing EPSPs in depressor and IPSPs in elevator motoneurones. 7. No connexions of either fore- or hindwing stretch receptors have been found with contralateral flight motoneurones. 8. Interganglionic connexions are made by both receptors. For example, both fore- and hindwing stretch receptors cause EPSPs upon the meso- and metathoracic first basalar motoneurones. 9. Stimulation of the axon of a stretch receptor with groups of three stimuli repeated every 50-100 msec thus simulating the pattern which it shows during flight, causes subthreshold waves of depolarization in depressor motoneurones. When summed with an unpatterned input, the stretch receptor is able to influence the production of spikes in motoneurones on each cycle. During flight, it is expected that the stretch receptor will influence the time at which a motoneurone will spike and hence have an effect on the amplitude of the upstroke and upon the phase relationship between spikes of motoneurones."} {"id": "PMID:168305", "title": "Proprioceptive motor control in fish respiration.", "content": "The response of single respiratory neurones in the medulla oblongata of carp to short twitches of individual respiratory muscles were analysed. The muscle contractions were obtained through automatic electrical stimulation and could be consistently elicited in a predetermined phase relation to the ventilatory cycle. The results show that, apart from nerve cells which take part in long-term processing of proprioceptive information from several sources, neurones also exist which possess the properties of elements of a peripheral proprioceptive control loop such as tension receptor neurones, length or stretch receptor neurones and motor neurones.", "contents": "Proprioceptive motor control in fish respiration. The response of single respiratory neurones in the medulla oblongata of carp to short twitches of individual respiratory muscles were analysed. The muscle contractions were obtained through automatic electrical stimulation and could be consistently elicited in a predetermined phase relation to the ventilatory cycle. The results show that, apart from nerve cells which take part in long-term processing of proprioceptive information from several sources, neurones also exist which possess the properties of elements of a peripheral proprioceptive control loop such as tension receptor neurones, length or stretch receptor neurones and motor neurones."} {"id": "PMID:168306", "title": "Influence of nitrate on fermentation pattern, molar growth yields and synthesis of cytochrome b in Propionibacterium pentosaceum.", "content": "Under anaerobic conditions, Propionibacterium pentosaceum reduces nitrate to nitrite until nitrate is exhausted from the medium when nitrite is converted into N2 or N2O. In the presence of nitrate, fermentation patterns for lactate, glycerol and pyruvate were different from those obtained during anaerobic growth without an inorganic electron acceptor. In the presence of these substrates, a drastic decrease in propionate formation was observed, some pyruvate accumulated during growth with lactate, and acetate was produced from glycerol. Acetate production from lactate and pyruvate was not influenced by the presence of nitrate. Furthermore, CO2 was produced by citric acid cycle activity. The fermentation pattern during nitrite reduction resembled that of P. pentosaceum grown anaerobically without an inorganic electron acceptor. Nitrits has a toxic effect, since bacteria inoculated into a medium with 9 mM-nitrite failed to grow. The cytochrome spectrum of anaerobically grown P. pentosaceum was similar with and without nitrate. In membrane fractions of bacteria grown anaerobically with nitrate, cytochrome b functioned in the transfer of electrons from lactate, glycerol I-phosphate and NADH to nitrate. Molar growth yeilds were increased in the presence of nitrate, indicating an increased production of ATP. This could be explained by citric acid cycle activity, and by ocidative phosphorylation coupled to nitrate reduction. Assuming that I mol ATP is formed in the electron transfer from lactate or glycerol I-phosphate to nitrate, and that 2 mol ATP are formed in the electron transfer from NADH to nitrate, YATP values (g dry wt bacteria/mol ATP) were obtained of between 5-0 and 12-6. The higher YATP values were similar to those obtained during anaerobic growth without an inorganic electron acceptor. This supports the assumptions about the efficiency of oxidative phosphorylation for electron transport to nitrate. Low YAPT values were found when high concentrations of nitrite (15 to 50 mM) accumulated, and were probably due to the toxic effect of nitrite.", "contents": "Influence of nitrate on fermentation pattern, molar growth yields and synthesis of cytochrome b in Propionibacterium pentosaceum. Under anaerobic conditions, Propionibacterium pentosaceum reduces nitrate to nitrite until nitrate is exhausted from the medium when nitrite is converted into N2 or N2O. In the presence of nitrate, fermentation patterns for lactate, glycerol and pyruvate were different from those obtained during anaerobic growth without an inorganic electron acceptor. In the presence of these substrates, a drastic decrease in propionate formation was observed, some pyruvate accumulated during growth with lactate, and acetate was produced from glycerol. Acetate production from lactate and pyruvate was not influenced by the presence of nitrate. Furthermore, CO2 was produced by citric acid cycle activity. The fermentation pattern during nitrite reduction resembled that of P. pentosaceum grown anaerobically without an inorganic electron acceptor. Nitrits has a toxic effect, since bacteria inoculated into a medium with 9 mM-nitrite failed to grow. The cytochrome spectrum of anaerobically grown P. pentosaceum was similar with and without nitrate. In membrane fractions of bacteria grown anaerobically with nitrate, cytochrome b functioned in the transfer of electrons from lactate, glycerol I-phosphate and NADH to nitrate. Molar growth yeilds were increased in the presence of nitrate, indicating an increased production of ATP. This could be explained by citric acid cycle activity, and by ocidative phosphorylation coupled to nitrate reduction. Assuming that I mol ATP is formed in the electron transfer from lactate or glycerol I-phosphate to nitrate, and that 2 mol ATP are formed in the electron transfer from NADH to nitrate, YATP values (g dry wt bacteria/mol ATP) were obtained of between 5-0 and 12-6. The higher YATP values were similar to those obtained during anaerobic growth without an inorganic electron acceptor. This supports the assumptions about the efficiency of oxidative phosphorylation for electron transport to nitrate. Low YAPT values were found when high concentrations of nitrite (15 to 50 mM) accumulated, and were probably due to the toxic effect of nitrite."} {"id": "PMID:168307", "title": "Purification and characterization of a polyphosphate kinase from Arthrobacter atrocyaneus.", "content": "Polyphosphate kinase, an enzyme which incorporated the gamma-phosphate of ATP into long-chain polyphosphate molecules, was purified more than 700-fold from Arthrobacter atrocyaneus by ammonium sulphate fractionation, DEAE-cellulose column chromatography and Ssphadex G-200 gel filtration. The enzyme had a broad pH optimum at 6-0 to 7-0 and required Mn2+ or Mg2+, histone, and inorganic phosphate for activity. The Km for Mn-ATP was 0-53 mM, and for inorganic phosphate was 1-67 mM. Free ATP concentrations greater than 8 muM inhibited the enzyme. Free Mn2+ or Mg2+ concentrations greater than 2 mM or 6 mM, respectively, were also inhibitory. Activity was strongly inhibited by 4 mM-ADP, 1 mM-PP1 or 20 mM-NaF. The effect of ADP might have resulted from reversing the equilibrium of the kinase reaction. The activation by phosphate ions might indicate a role for the enzyme in regulating intracellular phosphate levels or maintaining a phosphorus reserve. The level of enzymic activity in the bacteria responded to changes in inorganic phosphate concentration in the medium. Basic proteins, such as protamine, could substitute for histone as activator. Proteins such as casein or bovine serum albunim would also substitute for histone but only in the absence of inorganic phosphate. The presence of a protein might be necessary to form a complex with the product, thus preventing reversal of the reaction in vitro. The reaction product was characterized, and found to be labile in hydroxylamine, base, and acid at 100 degrees C. It behaved as a long-chain-polyphosphate molecule on chromatography in an Ebel's solvent. The enzymic activity was therefore not that of a protein kinase.", "contents": "Purification and characterization of a polyphosphate kinase from Arthrobacter atrocyaneus. Polyphosphate kinase, an enzyme which incorporated the gamma-phosphate of ATP into long-chain polyphosphate molecules, was purified more than 700-fold from Arthrobacter atrocyaneus by ammonium sulphate fractionation, DEAE-cellulose column chromatography and Ssphadex G-200 gel filtration. The enzyme had a broad pH optimum at 6-0 to 7-0 and required Mn2+ or Mg2+, histone, and inorganic phosphate for activity. The Km for Mn-ATP was 0-53 mM, and for inorganic phosphate was 1-67 mM. Free ATP concentrations greater than 8 muM inhibited the enzyme. Free Mn2+ or Mg2+ concentrations greater than 2 mM or 6 mM, respectively, were also inhibitory. Activity was strongly inhibited by 4 mM-ADP, 1 mM-PP1 or 20 mM-NaF. The effect of ADP might have resulted from reversing the equilibrium of the kinase reaction. The activation by phosphate ions might indicate a role for the enzyme in regulating intracellular phosphate levels or maintaining a phosphorus reserve. The level of enzymic activity in the bacteria responded to changes in inorganic phosphate concentration in the medium. Basic proteins, such as protamine, could substitute for histone as activator. Proteins such as casein or bovine serum albunim would also substitute for histone but only in the absence of inorganic phosphate. The presence of a protein might be necessary to form a complex with the product, thus preventing reversal of the reaction in vitro. The reaction product was characterized, and found to be labile in hydroxylamine, base, and acid at 100 degrees C. It behaved as a long-chain-polyphosphate molecule on chromatography in an Ebel's solvent. The enzymic activity was therefore not that of a protein kinase."} {"id": "PMID:168308", "title": "Taxonomy of the Clostridia: ribosomal ribonucleic acid homologies among the species.", "content": "rRNA homologies have been determined on reference strains representing 56 species of Clostridium. Competition experiments using tritium-labelled 23S rRNA were employed. The majority of the species had DNA with 27 to 28% guanine plus cytosine (%GC). These fell into rRNA homology groups I and II, which were well defined, and a third group which consisted of species which did not belong in groups I and II. Species whose DNA was 41 to 45% GC comprised a fourth group. Thirty species were placed into rRNA homology group I on the basis of having 50% or greater homology with Clostridium butyricum, C. perfringens, C. carnis, C. sporogenes, C. novyi or C. pasteurianum. Ten subgroups were delineated in homology group I. Species in each subgroup either had high homology with a particular reference species or a similar pattern of homologies to all of the reference organisms. The eleven species in rRNA homology group II had 69% or greater homology to C. lituseburense. Species in groups I and II had intergroup homologies of 20 to 40%. The six species in group II had very low homologies with groups I and II. Negligible homology also resulted when five of the species were tested against the sixth, C. ramosum. The five species having DNA with 41 to 45% GC were C. innocuum, C. sphenoides, C. indolis, C. barkeri and C. orotic um. Little rRNA homology was apparent between C. innocuum and the other high % GC species or with several Bacillus species having similar %GC DNA. Correlations between homology results and phenotypic characteristics are discussed.", "contents": "Taxonomy of the Clostridia: ribosomal ribonucleic acid homologies among the species. rRNA homologies have been determined on reference strains representing 56 species of Clostridium. Competition experiments using tritium-labelled 23S rRNA were employed. The majority of the species had DNA with 27 to 28% guanine plus cytosine (%GC). These fell into rRNA homology groups I and II, which were well defined, and a third group which consisted of species which did not belong in groups I and II. Species whose DNA was 41 to 45% GC comprised a fourth group. Thirty species were placed into rRNA homology group I on the basis of having 50% or greater homology with Clostridium butyricum, C. perfringens, C. carnis, C. sporogenes, C. novyi or C. pasteurianum. Ten subgroups were delineated in homology group I. Species in each subgroup either had high homology with a particular reference species or a similar pattern of homologies to all of the reference organisms. The eleven species in rRNA homology group II had 69% or greater homology to C. lituseburense. Species in groups I and II had intergroup homologies of 20 to 40%. The six species in group II had very low homologies with groups I and II. Negligible homology also resulted when five of the species were tested against the sixth, C. ramosum. The five species having DNA with 41 to 45% GC were C. innocuum, C. sphenoides, C. indolis, C. barkeri and C. orotic um. Little rRNA homology was apparent between C. innocuum and the other high % GC species or with several Bacillus species having similar %GC DNA. Correlations between homology results and phenotypic characteristics are discussed."} {"id": "PMID:168309", "title": "Temporal genetic mapping in the blue-green alga Anacystis nidulans using ethyl methanesulphonate.", "content": "Cultures of the blue-green alga Anacytis nidulans were synchronized with respect to DNA synthesis as well as cell division. Application of ethyl methanesulphonate at different stages of replication resulted in a peak of mutation frequency for different genetic markers; this peak can be accounted for in terms of the involvement of repair processes. A temporal map of 19 markers has been constructed by this method. Comparison of gene position obtained by temporal mapping indicates that either bidirectional replication or unidirectional replication from more than one origin occurs.", "contents": "Temporal genetic mapping in the blue-green alga Anacystis nidulans using ethyl methanesulphonate. Cultures of the blue-green alga Anacytis nidulans were synchronized with respect to DNA synthesis as well as cell division. Application of ethyl methanesulphonate at different stages of replication resulted in a peak of mutation frequency for different genetic markers; this peak can be accounted for in terms of the involvement of repair processes. A temporal map of 19 markers has been constructed by this method. Comparison of gene position obtained by temporal mapping indicates that either bidirectional replication or unidirectional replication from more than one origin occurs."} {"id": "PMID:168311", "title": "The action of Vibrio cholerae and Corynebacterium diphtheriae neuraminidases on the Sendai virus receptor of human erythrocytes.", "content": "Studies of the Sendai virus haemagglutinin receptor on the human erythrocyte surface have confirmed that it involves 2 leads to 3 linked sialic acid. Because the primary specificity of Vibrio cholerae neuraminidase is for this linkage, it is able to compete with the virus for the receptor, to which it adsorbs strongly at low temperatures. Corynebacterium diphtheriae neuraminidase, whose principal specificity is for a sialic acid linkage other than 2 leads to 3, does not easily remove Sendai virus receptors, nor does it adsorb to the erythrocyte surface. A new definition of the term \"receptor-destroying enzyme\" is given which takes both enzyme and virus specificity into account, and a modified assay method is suggested in order to overcome the problems due to enzyme adsorption.", "contents": "The action of Vibrio cholerae and Corynebacterium diphtheriae neuraminidases on the Sendai virus receptor of human erythrocytes. Studies of the Sendai virus haemagglutinin receptor on the human erythrocyte surface have confirmed that it involves 2 leads to 3 linked sialic acid. Because the primary specificity of Vibrio cholerae neuraminidase is for this linkage, it is able to compete with the virus for the receptor, to which it adsorbs strongly at low temperatures. Corynebacterium diphtheriae neuraminidase, whose principal specificity is for a sialic acid linkage other than 2 leads to 3, does not easily remove Sendai virus receptors, nor does it adsorb to the erythrocyte surface. A new definition of the term \"receptor-destroying enzyme\" is given which takes both enzyme and virus specificity into account, and a modified assay method is suggested in order to overcome the problems due to enzyme adsorption."} {"id": "PMID:168312", "title": "Individual differences in compensatory rebound of REM sleep, with particular reference to their relationship to personality and behavioral characteristics.", "content": "In subjecting 14 healthy university students to partial differential rapid eye movement (REM) sleep deprivation (PDRD), the compensatory rebound of REM sleep during the next night was determined, and showed fairly substantial individual differences in the increased percentage of REM sleep time. This rate was approximately the same for the same individual for two sleep recordings. These individual differences had no positive correlation with the decreased rate of REM time in the PDRD nights or with the percentage of REM time in the baseline night. Therefore, the individual differences in the increased percentage of REM time can be presumed to reflect individual differences in need for deprived REM sleep. Next, we looked into the relationship between the individual subject's personality and behavior characteristics, and his increased percentage of REM time. This revealed that the individuals who were extrovertive, active, optimistic, showy, and who had many friends had significantly higher increases in the percentage of REM time than the individuals who were introvertive, neurotic, inactive, nervous, modest, and who had few friends. Also discussed was the neurophysiological and biochemical basis of the central nervous system as the background for the relationship between the personality and behavioral characteristics and the increased percentage of REM sleep time.", "contents": "Individual differences in compensatory rebound of REM sleep, with particular reference to their relationship to personality and behavioral characteristics. In subjecting 14 healthy university students to partial differential rapid eye movement (REM) sleep deprivation (PDRD), the compensatory rebound of REM sleep during the next night was determined, and showed fairly substantial individual differences in the increased percentage of REM sleep time. This rate was approximately the same for the same individual for two sleep recordings. These individual differences had no positive correlation with the decreased rate of REM time in the PDRD nights or with the percentage of REM time in the baseline night. Therefore, the individual differences in the increased percentage of REM time can be presumed to reflect individual differences in need for deprived REM sleep. Next, we looked into the relationship between the individual subject's personality and behavior characteristics, and his increased percentage of REM time. This revealed that the individuals who were extrovertive, active, optimistic, showy, and who had many friends had significantly higher increases in the percentage of REM time than the individuals who were introvertive, neurotic, inactive, nervous, modest, and who had few friends. Also discussed was the neurophysiological and biochemical basis of the central nervous system as the background for the relationship between the personality and behavioral characteristics and the increased percentage of REM sleep time."} {"id": "PMID:168313", "title": "The terminal autonomic nervous system in the pancreas of newts. Electron microscopic investigations using acetylcholinesterase and zinc iodide-osmium tetroxide reactions.", "content": "The intrinsic innervation in the pancreas of newts Triturus vulgaris, Tr. montandoni and Notophthalmus. All the investigated species display: cholinergic innervation better developed than adrenergic, no qualitative differences regarding the fine structure of nerve fibers and terminals as compared to that previously described in the pancreas or in other glands, axo-axonal contacts. Their functional signification as peripheric synapses is suggested. Frequently neuro-glandular junctions with or without membrane specializations. The occurrence of the latter is discussed in connection with peripheral transmission of nervous impulse.", "contents": "The terminal autonomic nervous system in the pancreas of newts. Electron microscopic investigations using acetylcholinesterase and zinc iodide-osmium tetroxide reactions. The intrinsic innervation in the pancreas of newts Triturus vulgaris, Tr. montandoni and Notophthalmus. All the investigated species display: cholinergic innervation better developed than adrenergic, no qualitative differences regarding the fine structure of nerve fibers and terminals as compared to that previously described in the pancreas or in other glands, axo-axonal contacts. Their functional signification as peripheric synapses is suggested. Frequently neuro-glandular junctions with or without membrane specializations. The occurrence of the latter is discussed in connection with peripheral transmission of nervous impulse."} {"id": "PMID:168315", "title": "Peripheral nerve involvement in Batten-Spielmeyer-Vogt's disease.", "content": "Electromyography and sensory and motor nerve conduction were studied in 23 patients with Batten-Spielmeyer-Vogt's disease (\"juvenile amaurotic idiocy\", cerebral ceroidlipofuscinosis). A slight to moderate slowing of the sensory conduction velocity was found in the median as well as in the sural nerve, more pronounced in the distal than in the proximal segments. The findings are interpreted as evidence of impaired transmission of the peripheral nerves in Batten-Spielmeyer-Vogt's disease.", "contents": "Peripheral nerve involvement in Batten-Spielmeyer-Vogt's disease. Electromyography and sensory and motor nerve conduction were studied in 23 patients with Batten-Spielmeyer-Vogt's disease (\"juvenile amaurotic idiocy\", cerebral ceroidlipofuscinosis). A slight to moderate slowing of the sensory conduction velocity was found in the median as well as in the sural nerve, more pronounced in the distal than in the proximal segments. The findings are interpreted as evidence of impaired transmission of the peripheral nerves in Batten-Spielmeyer-Vogt's disease."} {"id": "PMID:168316", "title": "Progressive multifocal leucoencephalopathy: remission with cytarabine.", "content": "A patient with a 14 year history of sarcoidosis developed a progressive left cerebral hemisphere lesion. The clinical diagnosis of progressive multifocal leucoencephalopathy was confirmed by brain biopsy and remission occurred after treatment with cytosine arabinoside.", "contents": "Progressive multifocal leucoencephalopathy: remission with cytarabine. A patient with a 14 year history of sarcoidosis developed a progressive left cerebral hemisphere lesion. The clinical diagnosis of progressive multifocal leucoencephalopathy was confirmed by brain biopsy and remission occurred after treatment with cytosine arabinoside."} {"id": "PMID:168317", "title": "Myxoedematous polyneuropathy: a light and electron microscopic study of the peripheral nerve and muscle.", "content": "Histopathological findings of biopsied peripheral nerve and muscle were studied in a case with myxoedematous polyneuropathy. The most striking findings in the sural nerve were segmental demyelination and onion bulb formation with scanty mucinous deposits in addition to marked loss of large myelinated nerve fibres. The peroneus brevis muscle revealed the association of neuropathic and myopathic changes. It is suggested that myxoedematous polyneuropathy might be intrinsic neuropathy due to metabolic disorder of Schwann cells related to hypothyroidism, resulting in segmental demyelination, not merely compressive neuropathy due to mucinous deposits in the peripheral nerves.", "contents": "Myxoedematous polyneuropathy: a light and electron microscopic study of the peripheral nerve and muscle. Histopathological findings of biopsied peripheral nerve and muscle were studied in a case with myxoedematous polyneuropathy. The most striking findings in the sural nerve were segmental demyelination and onion bulb formation with scanty mucinous deposits in addition to marked loss of large myelinated nerve fibres. The peroneus brevis muscle revealed the association of neuropathic and myopathic changes. It is suggested that myxoedematous polyneuropathy might be intrinsic neuropathy due to metabolic disorder of Schwann cells related to hypothyroidism, resulting in segmental demyelination, not merely compressive neuropathy due to mucinous deposits in the peripheral nerves."} {"id": "PMID:168318", "title": "Peripheral neuropathy in acrodermatitis chronica atrophicans (Herxheimer).", "content": "Acrodermatitis chronica atrophicans is a dermatological condition that takes a chronically progressive course and finally leads to a widespread atrophy of the skin. Involvement of the peripheral nervous system is frequently observed, predominantly a sensory polyneuropathy. General reactions, the effect of penicillin treatment, the histological findings, and reports concerning a communicable agent transmittable from human to human as well in tissue cultures point to an infectious disease. Acrodermatitis chronica atrophicans follows a peculiar geographical distribution forming clusters of high prevalence in certain regions. Transmission by ticks is suggested.", "contents": "Peripheral neuropathy in acrodermatitis chronica atrophicans (Herxheimer). Acrodermatitis chronica atrophicans is a dermatological condition that takes a chronically progressive course and finally leads to a widespread atrophy of the skin. Involvement of the peripheral nervous system is frequently observed, predominantly a sensory polyneuropathy. General reactions, the effect of penicillin treatment, the histological findings, and reports concerning a communicable agent transmittable from human to human as well in tissue cultures point to an infectious disease. Acrodermatitis chronica atrophicans follows a peculiar geographical distribution forming clusters of high prevalence in certain regions. Transmission by ticks is suggested."} {"id": "PMID:168319", "title": "A case of type 1 muscle fibre hypotrophy and internal nuclei.", "content": "A 14 year old boy was diagnosed as suffering from type 1 muscle fibre hypotrophy with internal nuclei. On histological examination of a biopsied muscle, there was selective hypotrophy of type 1 muscle fibre with internal nuclei, and focal degenerative changes were seen in a few type 1 fibres. The small type 1 fibres were arranged in small or large groups in one bundle. An EMG study of moderately weak muscles revealed low amplitude and short duration motor unit potentials as well as normal potentials and no spontaneous discharges. The H reflexes were abnormally low in amplitude comapred with the M response. The histological and electrophysiological findings suggested that the type 1 fibre involvement in the present case may have a neurogenic basis. It is likely that the clinical features of the reported cases are too variable for a single clinical entity.", "contents": "A case of type 1 muscle fibre hypotrophy and internal nuclei. A 14 year old boy was diagnosed as suffering from type 1 muscle fibre hypotrophy with internal nuclei. On histological examination of a biopsied muscle, there was selective hypotrophy of type 1 muscle fibre with internal nuclei, and focal degenerative changes were seen in a few type 1 fibres. The small type 1 fibres were arranged in small or large groups in one bundle. An EMG study of moderately weak muscles revealed low amplitude and short duration motor unit potentials as well as normal potentials and no spontaneous discharges. The H reflexes were abnormally low in amplitude comapred with the M response. The histological and electrophysiological findings suggested that the type 1 fibre involvement in the present case may have a neurogenic basis. It is likely that the clinical features of the reported cases are too variable for a single clinical entity."} {"id": "PMID:168320", "title": "Tuberous sclerosis and Klippel-Trenaunay-Weber syndromes. Association of two complete phakomatoses in a single individual.", "content": "Tuberous sclerosis and Klippel-Trenaunay-Weber (KTW) syndromes are phakomatoses which are believed to be inherited separately. A 41 year old woman presented with the classic features of tuberous sclerosis: adenoma sebaceum, mental retardation, and seizures. In addition, the diagnostic triad of KTW involved the left lower limb: cutaneous naevi, a vascular anomaly, and osteohypertrophy. Arteriography documented the presence of visceral tumours and an arteriovenous malformation of the leg. This is the first reported association of the fully-developed symptomatology of tuberous sclerosis and KTW in one person.", "contents": "Tuberous sclerosis and Klippel-Trenaunay-Weber syndromes. Association of two complete phakomatoses in a single individual. Tuberous sclerosis and Klippel-Trenaunay-Weber (KTW) syndromes are phakomatoses which are believed to be inherited separately. A 41 year old woman presented with the classic features of tuberous sclerosis: adenoma sebaceum, mental retardation, and seizures. In addition, the diagnostic triad of KTW involved the left lower limb: cutaneous naevi, a vascular anomaly, and osteohypertrophy. Arteriography documented the presence of visceral tumours and an arteriovenous malformation of the leg. This is the first reported association of the fully-developed symptomatology of tuberous sclerosis and KTW in one person."} {"id": "PMID:168321", "title": "Myasthenic decrement and myasthenic myopathy. A study on the effects of thymectomy.", "content": "Motor unit action potentials, M responses to repetitive nerve stimulation, and anticholinesterase tests were investigated in 12 myasthenic patients before and after thymectomy. In six of them the endarterial acetylcholine test was also carried out. Responsiveness to ACTH or to prednisone treatment was evaluated before and after thymectomy. The typical myasthenic presynaptic disorders were improved by thymectomy, while signs of myasthenic myopathy (according to Rowland's definition) were apparently increased. This process of 'functional myopathophanerosis' is discussed and explained in terms of a previous presynaptic disorder blocking the voluntary recruitment threshold of those motor units which are most affected at both presynaptic and postsynaptic level.", "contents": "Myasthenic decrement and myasthenic myopathy. A study on the effects of thymectomy. Motor unit action potentials, M responses to repetitive nerve stimulation, and anticholinesterase tests were investigated in 12 myasthenic patients before and after thymectomy. In six of them the endarterial acetylcholine test was also carried out. Responsiveness to ACTH or to prednisone treatment was evaluated before and after thymectomy. The typical myasthenic presynaptic disorders were improved by thymectomy, while signs of myasthenic myopathy (according to Rowland's definition) were apparently increased. This process of 'functional myopathophanerosis' is discussed and explained in terms of a previous presynaptic disorder blocking the voluntary recruitment threshold of those motor units which are most affected at both presynaptic and postsynaptic level."} {"id": "PMID:168322", "title": "Acrylamide encephaloneuropathy due to well water pollution.", "content": "All five members of a family developed subacutely mental confusion and/or truncal ataxia. Symptoms and signs of polyneuropathy were seen later. The well water in the patients' home contained 400 ppm acrylamide. The present cases are unique in that they are cases of acrylamide poisoning induced by oral intake and percutaneous penetration, and that central nervous system symptoms were prominent.", "contents": "Acrylamide encephaloneuropathy due to well water pollution. All five members of a family developed subacutely mental confusion and/or truncal ataxia. Symptoms and signs of polyneuropathy were seen later. The well water in the patients' home contained 400 ppm acrylamide. The present cases are unique in that they are cases of acrylamide poisoning induced by oral intake and percutaneous penetration, and that central nervous system symptoms were prominent."} {"id": "PMID:168323", "title": "[Atypical juvenile neurolipidosis. Ultrastructural study of a cerebral biopsy].", "content": "Electron-microscopic findings on a brain biopsy in a 9-year-old male affected by juvenile lipidosis are reported. Two types of neuronal cytosomes were discribed: lamellar concentric bodies, resembling membranous cytoplasmic bodies, and polymorphous complex bodies, unit membrane bound including various material, mostly resembling lipofuscin. The same storage was found in glial and endothelial cells. Neurochemical data failed to pin-point any specific abnormalities. The present case cannot be classified in the category of neuronal ceroid-lipofuscinosis but seems similar to certain reported cases of atypicalneurolipidosis.", "contents": "[Atypical juvenile neurolipidosis. Ultrastructural study of a cerebral biopsy]. Electron-microscopic findings on a brain biopsy in a 9-year-old male affected by juvenile lipidosis are reported. Two types of neuronal cytosomes were discribed: lamellar concentric bodies, resembling membranous cytoplasmic bodies, and polymorphous complex bodies, unit membrane bound including various material, mostly resembling lipofuscin. The same storage was found in glial and endothelial cells. Neurochemical data failed to pin-point any specific abnormalities. The present case cannot be classified in the category of neuronal ceroid-lipofuscinosis but seems similar to certain reported cases of atypicalneurolipidosis."} {"id": "PMID:168324", "title": "Therapeutic percutaneous embolization for extra-axial vascular lesions of the head, neck, and spine.", "content": "Therapeutic percutaneous embolization of extra-axial vascular tumors and arteriovenous malformations was performed 41 times in 27 patients. Twenty-one patients (78%) had a clinically favorable result. In 11 of these patients, the procedure was preoperative and caused a dramatic reduction of surgical blood loss. In the remaining 10 patients with a favorable result, therapeutic embolization alone resulted in a significant clinical amelioration documented by a detailed follow-up varying from 2 to 5 years. In patients with uncontrollable epistaxis, the procedure was life-saving. The guidelines and instrumentation for a safe and effective technique are presented, based on the authors' experience with more than 100 cases of vascular lesions of the brain and spinal cord. A low-viscosity silicone polymer was developed by the authors and used clinically as an intravascular adhesive for the embolization of vascular tumors.", "contents": "Therapeutic percutaneous embolization for extra-axial vascular lesions of the head, neck, and spine. Therapeutic percutaneous embolization of extra-axial vascular tumors and arteriovenous malformations was performed 41 times in 27 patients. Twenty-one patients (78%) had a clinically favorable result. In 11 of these patients, the procedure was preoperative and caused a dramatic reduction of surgical blood loss. In the remaining 10 patients with a favorable result, therapeutic embolization alone resulted in a significant clinical amelioration documented by a detailed follow-up varying from 2 to 5 years. In patients with uncontrollable epistaxis, the procedure was life-saving. The guidelines and instrumentation for a safe and effective technique are presented, based on the authors' experience with more than 100 cases of vascular lesions of the brain and spinal cord. A low-viscosity silicone polymer was developed by the authors and used clinically as an intravascular adhesive for the embolization of vascular tumors."} {"id": "PMID:168325", "title": "Critical evaluation of hepatic scintiangiography for neoplastic tumors of the liver.", "content": "Dynamic hepatic scintiangiography increases the specificity of diagnosis of space-occupying lesions of the liver seen on hepatic scintigraphy. The purpose of this study was to evaluate and compare critically this procedure with histologic and radiopaque diagnosis in the evaluation of suspected hepatic neoplasms. Ninety-two patients had hepatic scintiangiography, scintigraphy, and histologic certification. In ten of these patients the findings of radiopaque arteriography were compared with those of hepatic scintiangiography. In all ten patients with hepatoma, the scintiangiographic and histologic observations correlated; nine of these ten patients had a \"tumor stain.\" Fifty-one of 59 patients with metastases to the liver had scinitangiograms that showed \"tumor stain.\" In 2 of these 59 patients, scintiangiography revealed tumor vascularity whereas the results of scintigraphy were normal. In two of four patients with metastases and two of six patients with hepatomas, scintiangiograms revealed \"tumor stain\" that was not evident on radiopaque afteriography. Conclusions from this study are: (A) neoplastic arterialization or \"tumor stain\" is more readily detected by scintiangiography than by radiopaque arteriography; (B) a normal scintigram and a \"tumor stain\" on the scintiangiogram in a patient with a known primary neoplasm outside the liver is suggestive of hepatic metastases; and (C) a normal scintigram and scintiangiogram make neoplastic involvement of the liver improbable. Dynamic hepatic scintiangiography is a simple, clinically useful method for increasing the specificity of diagnosis of diagnosis of space-occupying lesions of the liver and should be part of the evaluation for possible neoplastic involvement.", "contents": "Critical evaluation of hepatic scintiangiography for neoplastic tumors of the liver. Dynamic hepatic scintiangiography increases the specificity of diagnosis of space-occupying lesions of the liver seen on hepatic scintigraphy. The purpose of this study was to evaluate and compare critically this procedure with histologic and radiopaque diagnosis in the evaluation of suspected hepatic neoplasms. Ninety-two patients had hepatic scintiangiography, scintigraphy, and histologic certification. In ten of these patients the findings of radiopaque arteriography were compared with those of hepatic scintiangiography. In all ten patients with hepatoma, the scintiangiographic and histologic observations correlated; nine of these ten patients had a \"tumor stain.\" Fifty-one of 59 patients with metastases to the liver had scinitangiograms that showed \"tumor stain.\" In 2 of these 59 patients, scintiangiography revealed tumor vascularity whereas the results of scintigraphy were normal. In two of four patients with metastases and two of six patients with hepatomas, scintiangiograms revealed \"tumor stain\" that was not evident on radiopaque afteriography. Conclusions from this study are: (A) neoplastic arterialization or \"tumor stain\" is more readily detected by scintiangiography than by radiopaque arteriography; (B) a normal scintigram and a \"tumor stain\" on the scintiangiogram in a patient with a known primary neoplasm outside the liver is suggestive of hepatic metastases; and (C) a normal scintigram and scintiangiogram make neoplastic involvement of the liver improbable. Dynamic hepatic scintiangiography is a simple, clinically useful method for increasing the specificity of diagnosis of diagnosis of space-occupying lesions of the liver and should be part of the evaluation for possible neoplastic involvement."} {"id": "PMID:168326", "title": "The value of hepatic scintiangiography and static liver scans in superior vena caval obstruction: Case report.", "content": "Isolated increased uptake of 99mTc-sulfur colloid in a static liver scan with associated hepatic scintiangiography demonstration of collateral venous circulation is pathognomonic for superior vena caval obstruction. A case with these findings is reported and the differential diagnosis of \"hot spots\" occurring in liver scanning is discussed.", "contents": "The value of hepatic scintiangiography and static liver scans in superior vena caval obstruction: Case report. Isolated increased uptake of 99mTc-sulfur colloid in a static liver scan with associated hepatic scintiangiography demonstration of collateral venous circulation is pathognomonic for superior vena caval obstruction. A case with these findings is reported and the differential diagnosis of \"hot spots\" occurring in liver scanning is discussed."} {"id": "PMID:168327", "title": "Evaluation of a rapid and simple technique for the radioimmunoassay of triiodothyronine (T3).", "content": "This report compares T3 measurements obtained on the same serum samples by a resinstrip technique and by another existing radioimmunoassay method. The samples analyzed were obtained from a total of 90 subjects who were clinically categorized as hypothyroid, normal, hyperthyroid, or euthyroid while taking estrogen-containing compounds or while pregnant. The correlation coefficient for all 90 sera with these two different techniques was 0.94. All subjects who were clinically euthyroid (32) had a normal serum T3 concentration by the resin-strip technique. Similarly, 23 clinically hyperthyroid patients had elevated serum T3 concentrations and 15 of 17 clinically hypothyroid patients had decreased serum T3 levels.", "contents": "Evaluation of a rapid and simple technique for the radioimmunoassay of triiodothyronine (T3). This report compares T3 measurements obtained on the same serum samples by a resinstrip technique and by another existing radioimmunoassay method. The samples analyzed were obtained from a total of 90 subjects who were clinically categorized as hypothyroid, normal, hyperthyroid, or euthyroid while taking estrogen-containing compounds or while pregnant. The correlation coefficient for all 90 sera with these two different techniques was 0.94. All subjects who were clinically euthyroid (32) had a normal serum T3 concentration by the resin-strip technique. Similarly, 23 clinically hyperthyroid patients had elevated serum T3 concentrations and 15 of 17 clinically hypothyroid patients had decreased serum T3 levels."} {"id": "PMID:168328", "title": "Enzymic formation of thiamine pyrophosphate in plants.", "content": "Evidence was presented by paper chromatographic analysis on the occurrence of an enzyme capable of catalyzing a pyrophosphate transfer from ATP to thiamine in green leaves of various plants. The exclusive localization of the enzyme activity in the 105,000 X g supernatant (in a soluble form) was demonstrated by differential centrifugation of a cell homogentae in 0.25 M sucrose. The enzyme was purified by column chromatography with DEAE-cellulose and by gel filtration with Sephadex G-150. The partially pruified preparation, while contaminated with detectable activity of acid phosphatase, lost the ability of utilizing thiamine monophosphate as the substrate in place of thiamine. These findings lead to the conclusion that thiamine pyrophosphate is formed in green leaves of plants through a direct pyrophosphorylation of thiamine in the presence of ATP and Mg.", "contents": "Enzymic formation of thiamine pyrophosphate in plants. Evidence was presented by paper chromatographic analysis on the occurrence of an enzyme capable of catalyzing a pyrophosphate transfer from ATP to thiamine in green leaves of various plants. The exclusive localization of the enzyme activity in the 105,000 X g supernatant (in a soluble form) was demonstrated by differential centrifugation of a cell homogentae in 0.25 M sucrose. The enzyme was purified by column chromatography with DEAE-cellulose and by gel filtration with Sephadex G-150. The partially pruified preparation, while contaminated with detectable activity of acid phosphatase, lost the ability of utilizing thiamine monophosphate as the substrate in place of thiamine. These findings lead to the conclusion that thiamine pyrophosphate is formed in green leaves of plants through a direct pyrophosphorylation of thiamine in the presence of ATP and Mg."} {"id": "PMID:168329", "title": "Cystic partially differentiated nephroblastoma.", "content": "An unusual cystic renal tumour is described which resembles, superficially, the solitary multilocular cyst of the kidney, but which shows appreciable amounts of proliferating undifferentiated renal blastema. We believe that this tumour represents a partially differentiated nephroblastoma and that, as such, it provides support for the theory that Wilms' tumour is capable of undergoing maturation to a fully differentiated, benign cystic lesion.", "contents": "Cystic partially differentiated nephroblastoma. An unusual cystic renal tumour is described which resembles, superficially, the solitary multilocular cyst of the kidney, but which shows appreciable amounts of proliferating undifferentiated renal blastema. We believe that this tumour represents a partially differentiated nephroblastoma and that, as such, it provides support for the theory that Wilms' tumour is capable of undergoing maturation to a fully differentiated, benign cystic lesion."} {"id": "PMID:168330", "title": "Macrophages in brain tumours induced transplacentally by N-ethyl-N-nitrosourea in rats: an electron-microscope study.", "content": "The fine structure of macrophages has been studied in experimental brain tumours induced transplacentally in BD-IX rats by a single intravenous injection of 30 mg of N-ethyl-N-nitrosourea per kg of body weight on the 15th day of gestation. The tumours, depending on their localisation and size, caused various lesions in the brain, namely axonal degeneration, loss of myelin, oedema, haemorrhage and cell necrosis. The tumours and the resulting alterations elicited a strong reaction by macrophages: activation of microglial cells in situ and infiltration of the brain by leucocytes, chiefly by monocytes. Since both microglial cells and monocytes underwent morphological changes, it was difficult, or impossible, to establish the origin of these reacting cells. In a few cases, however, microglial cells and monocytes could be distinguished; this indicated that microglial cells were still being activated and leucocytes were still entering the brain. Various stages of activity of macrophages have been described: the number of lysosomes and cytoplasmic inclusions were thought to indicate activation, phagocytosis and repletion. Activation is characterised by an increase of lysosomes and frequent cell divisions. Phagocytic activity is accompanied by the appearance of inclusions which varied in different lesions: protein-like material in oedema, remnants of erythrocytes in haemorrhages and myelin-lamellae with lipid droplets in demyelination. These various inclusions were frequently present in the same cell, since the different lesions not uncommonly occurred at the same time. In the stage of repletion macrophages contained mainly lipid droplets and unidentifiable debris in their abundant cytoplasm and thus corresponded to the compound granular corpuscles.", "contents": "Macrophages in brain tumours induced transplacentally by N-ethyl-N-nitrosourea in rats: an electron-microscope study. The fine structure of macrophages has been studied in experimental brain tumours induced transplacentally in BD-IX rats by a single intravenous injection of 30 mg of N-ethyl-N-nitrosourea per kg of body weight on the 15th day of gestation. The tumours, depending on their localisation and size, caused various lesions in the brain, namely axonal degeneration, loss of myelin, oedema, haemorrhage and cell necrosis. The tumours and the resulting alterations elicited a strong reaction by macrophages: activation of microglial cells in situ and infiltration of the brain by leucocytes, chiefly by monocytes. Since both microglial cells and monocytes underwent morphological changes, it was difficult, or impossible, to establish the origin of these reacting cells. In a few cases, however, microglial cells and monocytes could be distinguished; this indicated that microglial cells were still being activated and leucocytes were still entering the brain. Various stages of activity of macrophages have been described: the number of lysosomes and cytoplasmic inclusions were thought to indicate activation, phagocytosis and repletion. Activation is characterised by an increase of lysosomes and frequent cell divisions. Phagocytic activity is accompanied by the appearance of inclusions which varied in different lesions: protein-like material in oedema, remnants of erythrocytes in haemorrhages and myelin-lamellae with lipid droplets in demyelination. These various inclusions were frequently present in the same cell, since the different lesions not uncommonly occurred at the same time. In the stage of repletion macrophages contained mainly lipid droplets and unidentifiable debris in their abundant cytoplasm and thus corresponded to the compound granular corpuscles."} {"id": "PMID:168331", "title": "Further studies on carrageenan-induced pleurisy in rats.", "content": "A study has been made of the exudate provoked by intrapleural carrageenan in rats. Various parameters have been measured including volume of exudate, numbers and types of cells. Pharmacological assay has shown the early release of histamine and 5HT into the exudate followed at later times by a release of prostaglandins, and a second release of histamine. The role of complement has been studied. Intrapleural injection of carrageenan after complement depletion produced a reduced migration of polymorphonuclear cells and also a reduction in volume of exudate. Prostaglandins remained unaffected by this treatment.", "contents": "Further studies on carrageenan-induced pleurisy in rats. A study has been made of the exudate provoked by intrapleural carrageenan in rats. Various parameters have been measured including volume of exudate, numbers and types of cells. Pharmacological assay has shown the early release of histamine and 5HT into the exudate followed at later times by a release of prostaglandins, and a second release of histamine. The role of complement has been studied. Intrapleural injection of carrageenan after complement depletion produced a reduced migration of polymorphonuclear cells and also a reduction in volume of exudate. Prostaglandins remained unaffected by this treatment."} {"id": "PMID:168332", "title": "Structural and functional characteristics of the microcirculation in neoplasms.", "content": "The microcirculation in a transplantable rat fibrosarcoma was investigated. The vasculature of the neoplasm consisted of irregular channels lined by plump endothelium which displayed mainly pentalaminar although a few heptalaminar junctions were also found. Few pericytes surround the endothelial layer while the basement-membrane varied in thickness and was often duplicated and triplicated. Challenge with histamine resulted in increased permeability in comparison with normal connective tissues similarly treated. The increased permeability was accompanied by the formation of interendothelial gaps in these irregular vascular channels. Carrageenan induced a leucocytic exudate in the neoplasm which, apart from an increase in the mononuclear concentration 2 wk after injection, varied little from normal connective tissues. It is concluded that the majority of vascular channels in this neoplasm bear some structural and functional relationship to small venules.", "contents": "Structural and functional characteristics of the microcirculation in neoplasms. The microcirculation in a transplantable rat fibrosarcoma was investigated. The vasculature of the neoplasm consisted of irregular channels lined by plump endothelium which displayed mainly pentalaminar although a few heptalaminar junctions were also found. Few pericytes surround the endothelial layer while the basement-membrane varied in thickness and was often duplicated and triplicated. Challenge with histamine resulted in increased permeability in comparison with normal connective tissues similarly treated. The increased permeability was accompanied by the formation of interendothelial gaps in these irregular vascular channels. Carrageenan induced a leucocytic exudate in the neoplasm which, apart from an increase in the mononuclear concentration 2 wk after injection, varied little from normal connective tissues. It is concluded that the majority of vascular channels in this neoplasm bear some structural and functional relationship to small venules."} {"id": "PMID:168334", "title": "Idiopathic thrombocytopenic purpura in children.", "content": "Idiopathic thrombocytopenic purpura in children 10 years of age or younger was observed to have a more favorable prognosis than in older children. Corticosteroid therapy in children judged to be at increased risk of serious hemorrhage resulted in a significantly greater number of patients with an early increase in platelets than was noted in a control group. All patients with chronic disease who responded to administration of a corticosteroid initially and then relapsed had some response to a subsequent course of therapy, although none had a sustained remission. In such patients, splenectomy was a more effective therapeutic measure than treatment with either a corticosteroid or a cytotoxic agent.", "contents": "Idiopathic thrombocytopenic purpura in children. Idiopathic thrombocytopenic purpura in children 10 years of age or younger was observed to have a more favorable prognosis than in older children. Corticosteroid therapy in children judged to be at increased risk of serious hemorrhage resulted in a significantly greater number of patients with an early increase in platelets than was noted in a control group. All patients with chronic disease who responded to administration of a corticosteroid initially and then relapsed had some response to a subsequent course of therapy, although none had a sustained remission. In such patients, splenectomy was a more effective therapeutic measure than treatment with either a corticosteroid or a cytotoxic agent."} {"id": "PMID:168335", "title": "Pseudohermaphroditis, with testes and a 46, XX karyotype.", "content": "A 14 4/12-year-old white girl, evaluated for progressive virilization and clitormegaly, was found to have the unusual combination of a 46, XX karyotype, well-developed Mullerian structures, and dysgenetic testes with Leydig cell hyperplasia. Although there have been previous case reports of 46, XX males, in all of these patients development of the Mullerian ducts had been suppressed. When contemporary classifications of human disorders of sexual differentation were reviewed, no report of a similar patient was found. We speculate that the genotype and phenotype in our patient correspond to the genetic intersexuality of the hornless goat, thereby raising the possibility that the human autosome may play a role in the control of sexual development.", "contents": "Pseudohermaphroditis, with testes and a 46, XX karyotype. A 14 4/12-year-old white girl, evaluated for progressive virilization and clitormegaly, was found to have the unusual combination of a 46, XX karyotype, well-developed Mullerian structures, and dysgenetic testes with Leydig cell hyperplasia. Although there have been previous case reports of 46, XX males, in all of these patients development of the Mullerian ducts had been suppressed. When contemporary classifications of human disorders of sexual differentation were reviewed, no report of a similar patient was found. We speculate that the genotype and phenotype in our patient correspond to the genetic intersexuality of the hornless goat, thereby raising the possibility that the human autosome may play a role in the control of sexual development."} {"id": "PMID:168336", "title": "Angiotensin-I-converting enzyme activity in idiopathic respiratory distress syndrome of the newborn infant and in experimental alveolar hypoxia in mice.", "content": "Serum angiotensin-I-converting enzyme activity was found to be elevated in infants with idiopathic respiratory distress syndrome when compared with healthy premature infants, normal infants, and acutely ill full-term infants. Serum and lung CE activity has been found to be elevated in mice exposed to hypobaric alveolar hypoxia which also stimulated renal renin production. These findings suggest that alveolar hypoxia stimulates the renin-angiotensin-aldosterone system and this system may be involved in the response to the stress of IRDS.", "contents": "Angiotensin-I-converting enzyme activity in idiopathic respiratory distress syndrome of the newborn infant and in experimental alveolar hypoxia in mice. Serum angiotensin-I-converting enzyme activity was found to be elevated in infants with idiopathic respiratory distress syndrome when compared with healthy premature infants, normal infants, and acutely ill full-term infants. Serum and lung CE activity has been found to be elevated in mice exposed to hypobaric alveolar hypoxia which also stimulated renal renin production. These findings suggest that alveolar hypoxia stimulates the renin-angiotensin-aldosterone system and this system may be involved in the response to the stress of IRDS."} {"id": "PMID:168338", "title": "Cytomegaloviremia in children with acute lymphocytic leukemia.", "content": "Leukocyte and urine cultures were done at monthly intervals in 36 children with acute lymphocytic leukemia known to be excreting cytomegalovirus in their or saliva in order to determine the relationship of viremia to clinical cytomegalic inclusion disease. Eleven of 36 (30.5%) patients had viremia. Viremia was related to clinical disease in only three patients; two with chorioretinitis and one with a CMV monomucleosis syndrom. However, the presence of viremia did not serve as a useful means to determine active CID. Viremic patients with CID all had elevated serum levels of IgM and multiple episodes of viremia. Viremia was not related to the duration, type or number of drugs used in immunosuppression, nor to the hematologic status of leukemia. Viremic patients received more blood transfusions than noviremic patients, but the administration of blood products could not be related to the acquisition of infection. Leukopenia, neutropenia, total lymphocyte count, fourfold rise or fall in complement-fixing titer, and viruria had no consistent relationship to viremia or clinical CID.", "contents": "Cytomegaloviremia in children with acute lymphocytic leukemia. Leukocyte and urine cultures were done at monthly intervals in 36 children with acute lymphocytic leukemia known to be excreting cytomegalovirus in their or saliva in order to determine the relationship of viremia to clinical cytomegalic inclusion disease. Eleven of 36 (30.5%) patients had viremia. Viremia was related to clinical disease in only three patients; two with chorioretinitis and one with a CMV monomucleosis syndrom. However, the presence of viremia did not serve as a useful means to determine active CID. Viremic patients with CID all had elevated serum levels of IgM and multiple episodes of viremia. Viremia was not related to the duration, type or number of drugs used in immunosuppression, nor to the hematologic status of leukemia. Viremic patients received more blood transfusions than noviremic patients, but the administration of blood products could not be related to the acquisition of infection. Leukopenia, neutropenia, total lymphocyte count, fourfold rise or fall in complement-fixing titer, and viruria had no consistent relationship to viremia or clinical CID."} {"id": "PMID:168339", "title": "Prenatal diagnosis and fetal pathology of I-cell disease (mucolipidosis type II).", "content": "Increased activity of several lysosomal hydrolases was demonstrated in amniotic fluid from a fifteenth week pregnancy in which the fetus had I-cell disease. Cultured cells from amniotic fluid had a decreased activity of the same enzymes. The diagnosis of I-cell disease was later confirmed by enzyme assays in cell cultures of fetal skin and by morphologic studies of several tissues from the aborted fetus. Electron microscopic studies of the fetal tissues and cultured fibroblasts had large numbers of typical inclusions of I-cell disease, thus substantiating the diagnosis and intrauterine manifestation of the disease. The results indicate that prenatal diagnosis of I-cell disease is possible with enzyme assays of amniotic fluid and in cultures of fetal cells from the fluid. Enzyme studies of amniotic fluid can provide a preliminary diagnosis within a few hours, but it is suggested that the definitive diagnosis should be based on assays in cultured cells from amniotic fluid.", "contents": "Prenatal diagnosis and fetal pathology of I-cell disease (mucolipidosis type II). Increased activity of several lysosomal hydrolases was demonstrated in amniotic fluid from a fifteenth week pregnancy in which the fetus had I-cell disease. Cultured cells from amniotic fluid had a decreased activity of the same enzymes. The diagnosis of I-cell disease was later confirmed by enzyme assays in cell cultures of fetal skin and by morphologic studies of several tissues from the aborted fetus. Electron microscopic studies of the fetal tissues and cultured fibroblasts had large numbers of typical inclusions of I-cell disease, thus substantiating the diagnosis and intrauterine manifestation of the disease. The results indicate that prenatal diagnosis of I-cell disease is possible with enzyme assays of amniotic fluid and in cultures of fetal cells from the fluid. Enzyme studies of amniotic fluid can provide a preliminary diagnosis within a few hours, but it is suggested that the definitive diagnosis should be based on assays in cultured cells from amniotic fluid."} {"id": "PMID:168344", "title": "Growth of calcium oxalate in gel systems.", "content": "Methods are described for growing calcium oxalate in silica and gelatin gels under different conditions. The results obtained indicate that, in silica gel, calcium oxalate grows into single individual crystals, twins, and rosettes. Bipyramidal calcium oxalate dihydrate crystals similar to those present in the urine of stone formers were prepared in the silica gel system. The gelatin gel offered a suitably structured substrate on which calcium oxalate monohydrate crystals grow into aggregates. The orientation pattern of calcium oxalate crystals suggests that the growth process is controlled by the stereospecificity of the gelatin medium supporting growth.", "contents": "Growth of calcium oxalate in gel systems. Methods are described for growing calcium oxalate in silica and gelatin gels under different conditions. The results obtained indicate that, in silica gel, calcium oxalate grows into single individual crystals, twins, and rosettes. Bipyramidal calcium oxalate dihydrate crystals similar to those present in the urine of stone formers were prepared in the silica gel system. The gelatin gel offered a suitably structured substrate on which calcium oxalate monohydrate crystals grow into aggregates. The orientation pattern of calcium oxalate crystals suggests that the growth process is controlled by the stereospecificity of the gelatin medium supporting growth."} {"id": "PMID:168345", "title": "Drug-biomolecule interactions: spin-probe study of effects of anesthetics on membrane lipids.", "content": "The electron spin resonance spectra of probes were used to study the organization and motion of molecules in hydrated stacked bilayer or liposome model membrane systems. The same steroid structures required for reduction of membrane permeability were required to produce well-ordered films of brain lipid. Alcohols and anesthetic agents influence the structure of model membranes, with their order of efficacy paralleling their pharmacological effectiveness. Spin probes were also used to demonstrate effects of calcium and local anesthetics on the rate of penetration of ascorbate into lipid bilayers.", "contents": "Drug-biomolecule interactions: spin-probe study of effects of anesthetics on membrane lipids. The electron spin resonance spectra of probes were used to study the organization and motion of molecules in hydrated stacked bilayer or liposome model membrane systems. The same steroid structures required for reduction of membrane permeability were required to produce well-ordered films of brain lipid. Alcohols and anesthetic agents influence the structure of model membranes, with their order of efficacy paralleling their pharmacological effectiveness. Spin probes were also used to demonstrate effects of calcium and local anesthetics on the rate of penetration of ascorbate into lipid bilayers."} {"id": "PMID:168346", "title": "Functional and structural changes in isolated rabbit liver mitochondria induced by fluorodichloromethane.", "content": "Fluorodichloromethane caused changes in substrate respiration rates and also in adenosine diphosphate (ADP)-stimulated rates of oxidation of both succinate and glutamate. Active swelling of mitochondria also occurred, but only in the presence of magnesium ion. ADP/O ratios were not significantly affected by the fluorocarbon. State IV respiration was stimulated, and the respiratory control ratio was linearly reduced with increased levels of fluorocarbon when succinate was used as substrate. Glutamate-stimulated respiration was greatly affected by the presence of the halocarbon but contrasted to the succinate responses. Low levels of fluorocarbon stimulated the state IV rate with glutamate whereas higher concentrations inhibited respiration. States III and IV respiration were completely inhibited by levels of 4.7 mg/ml of fluorodichloromethane when the nicotinamide adenine dinucleatide (NADH)-linked substrate was used. The NADH-linked substrate was more sensitive to the fluorocarbon treatment than the flavoprotein-linked substrate. The respiratory control ratio reached 1.0 at one-half the concentration required to elicit the same response with the flavoprotein-linked substrate, which suggested that NADH-dehydrogenase was inhibited. Active swelling of mitochondria occurred in the presence of magnesium and fluorocarbon, greatly exceeding controls, suggesting a loss of structural integrity and osmoregulation capacity. Increased rates of reduction of exogenously added cytochrome c also suggested changes in membrane integrity at higher fluorocarbon site of action of this compound is probably not the NADH-dehydrogenase system but the membrane system per se. Structural changes in the membrane system could account for the reported respiratory inhibition.", "contents": "Functional and structural changes in isolated rabbit liver mitochondria induced by fluorodichloromethane. Fluorodichloromethane caused changes in substrate respiration rates and also in adenosine diphosphate (ADP)-stimulated rates of oxidation of both succinate and glutamate. Active swelling of mitochondria also occurred, but only in the presence of magnesium ion. ADP/O ratios were not significantly affected by the fluorocarbon. State IV respiration was stimulated, and the respiratory control ratio was linearly reduced with increased levels of fluorocarbon when succinate was used as substrate. Glutamate-stimulated respiration was greatly affected by the presence of the halocarbon but contrasted to the succinate responses. Low levels of fluorocarbon stimulated the state IV rate with glutamate whereas higher concentrations inhibited respiration. States III and IV respiration were completely inhibited by levels of 4.7 mg/ml of fluorodichloromethane when the nicotinamide adenine dinucleatide (NADH)-linked substrate was used. The NADH-linked substrate was more sensitive to the fluorocarbon treatment than the flavoprotein-linked substrate. The respiratory control ratio reached 1.0 at one-half the concentration required to elicit the same response with the flavoprotein-linked substrate, which suggested that NADH-dehydrogenase was inhibited. Active swelling of mitochondria occurred in the presence of magnesium and fluorocarbon, greatly exceeding controls, suggesting a loss of structural integrity and osmoregulation capacity. Increased rates of reduction of exogenously added cytochrome c also suggested changes in membrane integrity at higher fluorocarbon site of action of this compound is probably not the NADH-dehydrogenase system but the membrane system per se. Structural changes in the membrane system could account for the reported respiratory inhibition."} {"id": "PMID:168347", "title": "Effects of chlorimipramine and lysergic acid diethylamide on efflux of precursor-formed 3-H-serotonin: correlations with serotonergic impulse flow.", "content": "The effects of d-lysergic acid diethylamide (LSD) and chlorimipramine (CIMI) on the firing rate of serotonergic (5-HT) neurons and on the in vivo efflux of 5-HT were investigated in parallel. A cerebroventricular perfusing technique was used to measure the efflux of 3-H-5-HT formed in vivo from 3-H-tryptophan. Impulse flow in serotonergic neurons was monitored by single unit recording from raphe (5-HT) neurons. Doses of LSD and CIMI, which caused a similar degree of inhibition of raphe cell firing, were found to affect 5-HT efflux differently. LSD, at both the 75, and 150 mug/kg doses, produced a similar decrease in 3-H-5-HT efflux. In contrast, CIMI at a low dose (5 mg/kg) did not reduce 5-HT efflux, despite an inhibition in impulse flow. At a high dose (20 mg/kg), CIMI produced an increase in 3-H-5-HT efflux. We conclude that 1) LSD decreased 3-H-5-HT efflux by directly inhibiting impulse flow in 5-HT neurons and/or by a local effect on 5-HT terminals and 2) a low dose of CIMI produces no net change in 3-H-5-HT efflux because a reduction in impulse flow-dependent 5-HT release compensates for blockade by CIMI of 5-HT reuptake.", "contents": "Effects of chlorimipramine and lysergic acid diethylamide on efflux of precursor-formed 3-H-serotonin: correlations with serotonergic impulse flow. The effects of d-lysergic acid diethylamide (LSD) and chlorimipramine (CIMI) on the firing rate of serotonergic (5-HT) neurons and on the in vivo efflux of 5-HT were investigated in parallel. A cerebroventricular perfusing technique was used to measure the efflux of 3-H-5-HT formed in vivo from 3-H-tryptophan. Impulse flow in serotonergic neurons was monitored by single unit recording from raphe (5-HT) neurons. Doses of LSD and CIMI, which caused a similar degree of inhibition of raphe cell firing, were found to affect 5-HT efflux differently. LSD, at both the 75, and 150 mug/kg doses, produced a similar decrease in 3-H-5-HT efflux. In contrast, CIMI at a low dose (5 mg/kg) did not reduce 5-HT efflux, despite an inhibition in impulse flow. At a high dose (20 mg/kg), CIMI produced an increase in 3-H-5-HT efflux. We conclude that 1) LSD decreased 3-H-5-HT efflux by directly inhibiting impulse flow in 5-HT neurons and/or by a local effect on 5-HT terminals and 2) a low dose of CIMI produces no net change in 3-H-5-HT efflux because a reduction in impulse flow-dependent 5-HT release compensates for blockade by CIMI of 5-HT reuptake."} {"id": "PMID:168348", "title": "Correlation between structure, behavioral activity and rate of biotransformation of some ACTH4-9 analogs.", "content": "The effect of substitutions in adrenocorticotropin (ACTH4-9) on extinction of pole-jumping avoidance behavior in intact rats was investigated systemically at two-dose levels. Simultaneous introduction of 4-methionine sulfoxide and 5-D-lysine, in combination with 9-phenylalanine, led to a 1000-fold increase in behavioral potency. The same substitutions induced a 1000-fold decrease in melanocyte-stimulating hormone activity. Incubations of 14-C-labeled ACTH4-9 analogs, prepared by reductive methylation, were carried out with plasma and brain extracts. The resulting metabolites were separated by paper electrophoresis and paper chromatography. The concentrations of nonmetabolized hexapeptides, which appeared to be almost entirely responsible for behavioral activity, were determined as a function of incubation time. The in vitro half-life of intact hexapeptides correlated with their behavioral activity. Therefore, the increase in behavioral potency as a result of amino acid substitutions can be explained, at least partly, by increased resistance against biotransformation.", "contents": "Correlation between structure, behavioral activity and rate of biotransformation of some ACTH4-9 analogs. The effect of substitutions in adrenocorticotropin (ACTH4-9) on extinction of pole-jumping avoidance behavior in intact rats was investigated systemically at two-dose levels. Simultaneous introduction of 4-methionine sulfoxide and 5-D-lysine, in combination with 9-phenylalanine, led to a 1000-fold increase in behavioral potency. The same substitutions induced a 1000-fold decrease in melanocyte-stimulating hormone activity. Incubations of 14-C-labeled ACTH4-9 analogs, prepared by reductive methylation, were carried out with plasma and brain extracts. The resulting metabolites were separated by paper electrophoresis and paper chromatography. The concentrations of nonmetabolized hexapeptides, which appeared to be almost entirely responsible for behavioral activity, were determined as a function of incubation time. The in vitro half-life of intact hexapeptides correlated with their behavioral activity. Therefore, the increase in behavioral potency as a result of amino acid substitutions can be explained, at least partly, by increased resistance against biotransformation."} {"id": "PMID:168349", "title": "Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes.", "content": "We have examined the effect of Delta1-tetrahydrocannabinol (delat1-THC) and 12 of its derivatives on the uptake of 3H-labeled norepinephrine (NE), dopamine (DA), serotonin (5-HT) gamma-aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Delta1-THC inhibits the accumulation of NE and 5-HT into hypothalamic preparations and DA into the corpus striatum with Ki values of about 12 to 25 muM while GABA uptake into cerebral cortical preparations is inhibited less (Ki = 140 muM). The affinities of delta6-THC, 7-hydroxy-delta1-THC, 7-hydroxy-delta6-THC and cannabidiol for 5-HT, NE and GABA transports are similar to values for delta1-THC, while cannabigerol, cannabinol and delta6-THC-7-oic acid have substantially less affinity. Thus, hydroxylation of C-7 in delta6-THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C-3(1) of ring C is critical for inhibition of NE, 5-HT and GABA uptake, since its acetylation or methylation abolishes activity. Inhibition of NE, DA, 5-HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of delta1-THC and delta6-THC and 5% of cannabidiol are fully soluble under our experimental conditions.", "contents": "Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes. We have examined the effect of Delta1-tetrahydrocannabinol (delat1-THC) and 12 of its derivatives on the uptake of 3H-labeled norepinephrine (NE), dopamine (DA), serotonin (5-HT) gamma-aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Delta1-THC inhibits the accumulation of NE and 5-HT into hypothalamic preparations and DA into the corpus striatum with Ki values of about 12 to 25 muM while GABA uptake into cerebral cortical preparations is inhibited less (Ki = 140 muM). The affinities of delta6-THC, 7-hydroxy-delta1-THC, 7-hydroxy-delta6-THC and cannabidiol for 5-HT, NE and GABA transports are similar to values for delta1-THC, while cannabigerol, cannabinol and delta6-THC-7-oic acid have substantially less affinity. Thus, hydroxylation of C-7 in delta6-THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C-3(1) of ring C is critical for inhibition of NE, 5-HT and GABA uptake, since its acetylation or methylation abolishes activity. Inhibition of NE, DA, 5-HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of delta1-THC and delta6-THC and 5% of cannabidiol are fully soluble under our experimental conditions."} {"id": "PMID:168350", "title": "Noradrenergic sensitivity of the cerebral cortex after chronic ethanol ingestion and withdrawal.", "content": "The effects of both chronic ethanol treatment and 3 days of ethanol withdrawal on the cyclic adenosine 3':5'-monophosphate (cAMP) response of cerebral cortical slices to norepinephrine (NE) were studied. ED50 cAMP responses for each group were determined using graded doses of NE. Chronic ethanol fed rats displayed subsensitivity to NE. There was a 4.3-fold shift of the dose-response curve to the right. Rats chronically fed ethanol and then put on 3 days of ethanol withdrawal developed supersensitivity. There was a 2.4-fold shift of the dose-response curve to the left. There was no difference in the maximal cAMP response observed in either the chronic alcohol or the chronic alcohol three day withdrawal experiments. It is possible that the biphasic modifications of effectors by ethanol ingestion and withdrawal from a subsensitive to a supersenitive is the result of one basic phenomenon.", "contents": "Noradrenergic sensitivity of the cerebral cortex after chronic ethanol ingestion and withdrawal. The effects of both chronic ethanol treatment and 3 days of ethanol withdrawal on the cyclic adenosine 3':5'-monophosphate (cAMP) response of cerebral cortical slices to norepinephrine (NE) were studied. ED50 cAMP responses for each group were determined using graded doses of NE. Chronic ethanol fed rats displayed subsensitivity to NE. There was a 4.3-fold shift of the dose-response curve to the right. Rats chronically fed ethanol and then put on 3 days of ethanol withdrawal developed supersensitivity. There was a 2.4-fold shift of the dose-response curve to the left. There was no difference in the maximal cAMP response observed in either the chronic alcohol or the chronic alcohol three day withdrawal experiments. It is possible that the biphasic modifications of effectors by ethanol ingestion and withdrawal from a subsensitive to a supersenitive is the result of one basic phenomenon."} {"id": "PMID:168351", "title": "Characterization of neuromuscular blocking action of piperidine derivatives.", "content": "cis and trans forms of 2-methyl-6-n-undecyl piperidines (C-11) are the main constituents of fire ant venom and have been studied for their mechanism of action on the neuromuscular transmission of the nerve-sartorius muscle preparation of frogs. At low concentrations (l times 10(-6)-2 times 10(-5) M), cis- and trans-C-11 irreversibly decreased the amplitude of spontaneous miniature end-plate potentials nerve-evoked end-plate potentials and iontophoretically induced acetylcholine depolarizations without changing the membrane potential. The quantal content and the focally recorded action potentials of nerve terminals remain unchanged. It was concluded that the piperidine derivatives block neuromuscular transmission postsynaptically through a decrease in the sensitivity of the end-plate membrane to acetylcholine. Pretreatment of the end-plate with d-tubocurarine did not effect the blocking action of trans-C-11. In direct binding experiments, trans-C-11 did not compete for the sites occupied by alpha-bungarotoxin, decamethonium, carbamylcholine and d-tubocurarine. These data suggest that trans-C-11 does not bind to the acetylcholine receptor site where the other cholinergic ligands have their affinity. It appears that these piperidine derivatives interfere with the coupling mechanism between acetylcholine-receptor binding and ionic conductance increases.", "contents": "Characterization of neuromuscular blocking action of piperidine derivatives. cis and trans forms of 2-methyl-6-n-undecyl piperidines (C-11) are the main constituents of fire ant venom and have been studied for their mechanism of action on the neuromuscular transmission of the nerve-sartorius muscle preparation of frogs. At low concentrations (l times 10(-6)-2 times 10(-5) M), cis- and trans-C-11 irreversibly decreased the amplitude of spontaneous miniature end-plate potentials nerve-evoked end-plate potentials and iontophoretically induced acetylcholine depolarizations without changing the membrane potential. The quantal content and the focally recorded action potentials of nerve terminals remain unchanged. It was concluded that the piperidine derivatives block neuromuscular transmission postsynaptically through a decrease in the sensitivity of the end-plate membrane to acetylcholine. Pretreatment of the end-plate with d-tubocurarine did not effect the blocking action of trans-C-11. In direct binding experiments, trans-C-11 did not compete for the sites occupied by alpha-bungarotoxin, decamethonium, carbamylcholine and d-tubocurarine. These data suggest that trans-C-11 does not bind to the acetylcholine receptor site where the other cholinergic ligands have their affinity. It appears that these piperidine derivatives interfere with the coupling mechanism between acetylcholine-receptor binding and ionic conductance increases."} {"id": "PMID:168352", "title": "Changes in mechanical events and adenosine 3',5'-monophosphate levels induced by enantiomers of isoproterenol in isolated rat atria and uteri.", "content": "Beta adrenergic receptors of rat atria and uteri were examined with the use of enantiomers of isoproterenol as agonists and mechanical responses and adenosine 3',5'-monophosphate (cyclic AMP) levels as measured effects. Assuming that stereoselectivity reflects the unique asymmetry of receptors, potency differences between the enantiomers are expected to provide a sensitive indication of ligand binding. All effects in each tissue were investigated under similar experimental conditions. Both isomers produced the same maximum effect on all measured responses. Enantiomeric potency differences (in log units) for positive chronotropic and inotropic responses and increases in cyclic AMP levels in atria were 3.31, 3.51 and 3.48, respectively. In uteri, the values for reduction of spontaneous contractile amplitude and increases in cyclic AMP were 2.90 and 2.79 log units, respectively. Even though these absolute values varied slightly with the experimental conditions, they were consistently smaller in uteri than in atria. In both tissues, dose-response curves for production of mechanical effects were greater than 2 log units to the left of those for increases in cyclic AMP levels. Regardless of the interpretation of this phenomenon, the results show the following. 1) The stereoselectivity for isoproterenol-induced effects is different between the two tissues at both levels of response. Therefore, it is suggested that this reflects dissimilar beta adrenergic receptor types in rat atrium vs. rat uterus. 2) The stereochemical selectivity for isoproterenol-induced mechanical effects and increases in cyclic AMP is the same in rat atrium and in rat uterus. Therefore, the data support the postulate that cyclic AMP is formed from interaction of isoproterenol with a receptor that is similar to the one activated to produce a mechanical effect.", "contents": "Changes in mechanical events and adenosine 3',5'-monophosphate levels induced by enantiomers of isoproterenol in isolated rat atria and uteri. Beta adrenergic receptors of rat atria and uteri were examined with the use of enantiomers of isoproterenol as agonists and mechanical responses and adenosine 3',5'-monophosphate (cyclic AMP) levels as measured effects. Assuming that stereoselectivity reflects the unique asymmetry of receptors, potency differences between the enantiomers are expected to provide a sensitive indication of ligand binding. All effects in each tissue were investigated under similar experimental conditions. Both isomers produced the same maximum effect on all measured responses. Enantiomeric potency differences (in log units) for positive chronotropic and inotropic responses and increases in cyclic AMP levels in atria were 3.31, 3.51 and 3.48, respectively. In uteri, the values for reduction of spontaneous contractile amplitude and increases in cyclic AMP were 2.90 and 2.79 log units, respectively. Even though these absolute values varied slightly with the experimental conditions, they were consistently smaller in uteri than in atria. In both tissues, dose-response curves for production of mechanical effects were greater than 2 log units to the left of those for increases in cyclic AMP levels. Regardless of the interpretation of this phenomenon, the results show the following. 1) The stereoselectivity for isoproterenol-induced effects is different between the two tissues at both levels of response. Therefore, it is suggested that this reflects dissimilar beta adrenergic receptor types in rat atrium vs. rat uterus. 2) The stereochemical selectivity for isoproterenol-induced mechanical effects and increases in cyclic AMP is the same in rat atrium and in rat uterus. Therefore, the data support the postulate that cyclic AMP is formed from interaction of isoproterenol with a receptor that is similar to the one activated to produce a mechanical effect."} {"id": "PMID:168353", "title": "Heterosynaptic facilitation in the giant cell of Aplysia.", "content": "1. Heterosynaptic facilitation, defined as an increase of the efficacy of synaptic transmission between a test interneurone and a post-synaptic neurone, produced by the stimulation of a separate pathway, was studied in the left pleural ganglion. The experimental procedure consisted of detecting the effects of a brief tetanus, applied to tentacular and tegumentary nerves, on the amplitude of monosynaptic and unitary post-synaptic potentials (p.s.p.s) recorded in the left giant cell and generated by stimulating the test interneurone every 10 sec. The membrane potential of the test interneurone was simultaneously recorded. 2. Following heterosynaptic stimulation, the amplitude of the test p.s.p. increased, after a delay of about 30 sec, up to 250% of its original size; this increase subsided after 2-3 min or more. 3. Only the interneurones producing in the giant cell the e.i.p.s.p. (excitatory-inhibitory post-synaptic potential) were affected by hetero-synaptic facilitation. Other interneuronal types showed no changes in their synaptic transmission on the giant cell after heterosynaptic stimulation. 4. Heterosynaptic stimulation did not produce either orthodromic or antidromic spikes in the test interneurones clearly indicating that facilitation of test p.s.p. did not result from increased spike activity in the test interneurone. 5. Often heterosynaptic facilitation of the test p.s.p. was observed due to spontaneous activity in the heterosynaptic pathway, demonstrating the normal occurrence of the phenomenon. 6. Iontophoretic injection of 5-HT at critical, presumably synaptic, sites in the neuropil, evoked a facilitation of the test p.s.p. similar to heterosynaptic facilitation. Only the e.i.p.s.p.s. were so affected by 5-HT. On the contrary, other p.s.p. types were depressed by 5-HT as a result of conductance changes in the left giant cells. 7. Both heterosynaptic facilitation and 5-HT facilitation were suppressed by the presence in the bath of 5-HT (10(-5) M) and of LSD-25 (3 X 10(-4) M). The action of injected 5-HT on the membrane conductance of the left giant cell was also depressed in the pressence of 5-HT in the bath, but was unaffected by LSD-25 (3 X 10(-4) M). 8. From the parallelism of properties of heterosynaptic and 5-HT facilitation, it is suggested that 5-HT is the probable transmitter mediating heterosynaptic facilitation. It seems likely that 5HT is released from the heterosynaptic pathway at the level of the synaptic ending of the test interneurone on to the giant cell and that it increases the efficacy of this synapse, probably acting on the quantity of synaptic transmitter liberated.", "contents": "Heterosynaptic facilitation in the giant cell of Aplysia. 1. Heterosynaptic facilitation, defined as an increase of the efficacy of synaptic transmission between a test interneurone and a post-synaptic neurone, produced by the stimulation of a separate pathway, was studied in the left pleural ganglion. The experimental procedure consisted of detecting the effects of a brief tetanus, applied to tentacular and tegumentary nerves, on the amplitude of monosynaptic and unitary post-synaptic potentials (p.s.p.s) recorded in the left giant cell and generated by stimulating the test interneurone every 10 sec. The membrane potential of the test interneurone was simultaneously recorded. 2. Following heterosynaptic stimulation, the amplitude of the test p.s.p. increased, after a delay of about 30 sec, up to 250% of its original size; this increase subsided after 2-3 min or more. 3. Only the interneurones producing in the giant cell the e.i.p.s.p. (excitatory-inhibitory post-synaptic potential) were affected by hetero-synaptic facilitation. Other interneuronal types showed no changes in their synaptic transmission on the giant cell after heterosynaptic stimulation. 4. Heterosynaptic stimulation did not produce either orthodromic or antidromic spikes in the test interneurones clearly indicating that facilitation of test p.s.p. did not result from increased spike activity in the test interneurone. 5. Often heterosynaptic facilitation of the test p.s.p. was observed due to spontaneous activity in the heterosynaptic pathway, demonstrating the normal occurrence of the phenomenon. 6. Iontophoretic injection of 5-HT at critical, presumably synaptic, sites in the neuropil, evoked a facilitation of the test p.s.p. similar to heterosynaptic facilitation. Only the e.i.p.s.p.s. were so affected by 5-HT. On the contrary, other p.s.p. types were depressed by 5-HT as a result of conductance changes in the left giant cells. 7. Both heterosynaptic facilitation and 5-HT facilitation were suppressed by the presence in the bath of 5-HT (10(-5) M) and of LSD-25 (3 X 10(-4) M). The action of injected 5-HT on the membrane conductance of the left giant cell was also depressed in the pressence of 5-HT in the bath, but was unaffected by LSD-25 (3 X 10(-4) M). 8. From the parallelism of properties of heterosynaptic and 5-HT facilitation, it is suggested that 5-HT is the probable transmitter mediating heterosynaptic facilitation. It seems likely that 5HT is released from the heterosynaptic pathway at the level of the synaptic ending of the test interneurone on to the giant cell and that it increases the efficacy of this synapse, probably acting on the quantity of synaptic transmitter liberated."} {"id": "PMID:168354", "title": "The possible role of cyclic AMP in the neurotrophic control of skeletal muscle.", "content": "1. Motoneurones provide trophic control of some of the functional characteristics of skeletal muscle fibres. This study has been designed to test whether the adenylate cyclase: cyclic AMP system may offer one potential mechanism for the mediation of neurotrophic regulation. 2. The concentration of cyclic AMP was measured at various intervals after muscle denervation. Muscle cyclic AMP concentration increases for the first 2 days after nerve section. It reaches a maximum value at 48 h and subsequently returns to the control value at 7 days. 3. Cyclic AMP concentration is unchanged by muscle disuse for the first 3 days following limb immobilization. Four days after immobilization, however, cyclic AMP increases in both the disused and contralateral control muscles. This phenomenon has been tentatively ascribed to some aspect of the inflammatory response. 4. Changing the level of nerve section, and therefore the length of the residual nerve stump, changes the temporal pattern of the increase in muscle cyclic AMP concentration. 5. Reinnervation of a denervated muscle produces a decrease in muscle cyclic AMP concentration. 6. It is concluded from the results that some aspect of nerve function provides trophic regulation of the muscle adenylate cyclase: cyclic AMP system. The mechanisms by which this regulation may be applied are considered in the Discussion.", "contents": "The possible role of cyclic AMP in the neurotrophic control of skeletal muscle. 1. Motoneurones provide trophic control of some of the functional characteristics of skeletal muscle fibres. This study has been designed to test whether the adenylate cyclase: cyclic AMP system may offer one potential mechanism for the mediation of neurotrophic regulation. 2. The concentration of cyclic AMP was measured at various intervals after muscle denervation. Muscle cyclic AMP concentration increases for the first 2 days after nerve section. It reaches a maximum value at 48 h and subsequently returns to the control value at 7 days. 3. Cyclic AMP concentration is unchanged by muscle disuse for the first 3 days following limb immobilization. Four days after immobilization, however, cyclic AMP increases in both the disused and contralateral control muscles. This phenomenon has been tentatively ascribed to some aspect of the inflammatory response. 4. Changing the level of nerve section, and therefore the length of the residual nerve stump, changes the temporal pattern of the increase in muscle cyclic AMP concentration. 5. Reinnervation of a denervated muscle produces a decrease in muscle cyclic AMP concentration. 6. It is concluded from the results that some aspect of nerve function provides trophic regulation of the muscle adenylate cyclase: cyclic AMP system. The mechanisms by which this regulation may be applied are considered in the Discussion."} {"id": "PMID:168355", "title": "Pancreatic acinar cells: effect of acetylcholine, pancreozymin, gastrin and secretin on membrane potential and resistance in vivo and in vitro.", "content": "1. Intracellular recordings of membrane potential and input resistance have been made in vivo and in vitro from the exocrine acinar cells of rat pancreas using indwelling glass micro-electrodes. 2. The resting cell membrane potential and input resistance in the in vivo experiments were not markedly different from the values obtained in the in vitro experiments. The effect of both acetylcholine (ACh) and pancreozymin (CCK-Pz) on the pancreas in vivo as well as in vitro was to reduce both the acinar cell membrane potential and the input resistance narkedly. The amplitude of the evoked depolarization and the change in input resistance evoked by supramaximal stimuli were of the same magnitude in both types of preparations. 3. Gastrin had an effect on the acinar cell potential and resistance which was indistinguishable from that of CCK-Pz or ACh. The effect of gastrin or CCK-Pz was, in contrast to that of ACh, not influenced by the presence of atropine. The reversal potential for the gastrin evoked potential change was about -20 mV. 4. Secretin in doses producing maximal volume secretion in vivo had no effect on acinar cell membrane potential and input resistance. 5. Dibutyryl cyclic AMP (5mM) and cyclic GMP (1mM) had no effect on cell membrane potential or resistance. 6. It is concluded that the in vitro superfused pancreas segment preparation is a useful model system in electrophysiological studies since it functions essentially as the in vivo preparation. In contrast to both gastrin and CCK-Pz, secretin has no effect on the bioelectrical properties of the acinar cells, indicating that there are no physiologically important secretin receptors in rat acinar cells.", "contents": "Pancreatic acinar cells: effect of acetylcholine, pancreozymin, gastrin and secretin on membrane potential and resistance in vivo and in vitro. 1. Intracellular recordings of membrane potential and input resistance have been made in vivo and in vitro from the exocrine acinar cells of rat pancreas using indwelling glass micro-electrodes. 2. The resting cell membrane potential and input resistance in the in vivo experiments were not markedly different from the values obtained in the in vitro experiments. The effect of both acetylcholine (ACh) and pancreozymin (CCK-Pz) on the pancreas in vivo as well as in vitro was to reduce both the acinar cell membrane potential and the input resistance narkedly. The amplitude of the evoked depolarization and the change in input resistance evoked by supramaximal stimuli were of the same magnitude in both types of preparations. 3. Gastrin had an effect on the acinar cell potential and resistance which was indistinguishable from that of CCK-Pz or ACh. The effect of gastrin or CCK-Pz was, in contrast to that of ACh, not influenced by the presence of atropine. The reversal potential for the gastrin evoked potential change was about -20 mV. 4. Secretin in doses producing maximal volume secretion in vivo had no effect on acinar cell membrane potential and input resistance. 5. Dibutyryl cyclic AMP (5mM) and cyclic GMP (1mM) had no effect on cell membrane potential or resistance. 6. It is concluded that the in vitro superfused pancreas segment preparation is a useful model system in electrophysiological studies since it functions essentially as the in vivo preparation. In contrast to both gastrin and CCK-Pz, secretin has no effect on the bioelectrical properties of the acinar cells, indicating that there are no physiologically important secretin receptors in rat acinar cells."} {"id": "PMID:168356", "title": "The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex.", "content": "1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied. Following stimulation of the lateral olfactory tract (l.o.t.) evoked potentials could be recorded from the cortical surface; these potentials consisted of an initial wave (the compound action potential of the l.o.t.) followed by a negative field potential which was associated with the synchronous excitation of many superficial excitatory synapses (population e.p.s.p.). Superimposed on the population e.p.s.p. was a number of positive peaks. These positive peaks reflect the synchronous discharge of many neurones and so have been called population spikes. 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres. 3. The evoked activity of individual cells in the cortex was depressed by ether and methoxyflurane. However, five of the twelve cells tested in ether showed an increase in their evoked activity at concentrations below 4-5%, but at higher concentrations these cells also became depressed. 4. Both ether and methoxyflurane depressed the sensitivity of cortical neurones to iontophoretically applied L-glutamate and may similarly depress the sensitivity of the post-synaptic membrane to the released transmitter substance. 5. Neither anaesthetic appeared to increase the threshold depolarization required for nerve impulse generation. Thus, the decrease of the discharge of the post-synaptic cells was primarily caused by a depression of chemical transmission. 6. Ether caused some cells in the cortex to alter their normal pattern of synaptically evoked discharge and both anaesthetics induced similar changes during excitation by glutamate.", "contents": "The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex. 1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied. Following stimulation of the lateral olfactory tract (l.o.t.) evoked potentials could be recorded from the cortical surface; these potentials consisted of an initial wave (the compound action potential of the l.o.t.) followed by a negative field potential which was associated with the synchronous excitation of many superficial excitatory synapses (population e.p.s.p.). Superimposed on the population e.p.s.p. was a number of positive peaks. These positive peaks reflect the synchronous discharge of many neurones and so have been called population spikes. 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres. 3. The evoked activity of individual cells in the cortex was depressed by ether and methoxyflurane. However, five of the twelve cells tested in ether showed an increase in their evoked activity at concentrations below 4-5%, but at higher concentrations these cells also became depressed. 4. Both ether and methoxyflurane depressed the sensitivity of cortical neurones to iontophoretically applied L-glutamate and may similarly depress the sensitivity of the post-synaptic membrane to the released transmitter substance. 5. Neither anaesthetic appeared to increase the threshold depolarization required for nerve impulse generation. Thus, the decrease of the discharge of the post-synaptic cells was primarily caused by a depression of chemical transmission. 6. Ether caused some cells in the cortex to alter their normal pattern of synaptically evoked discharge and both anaesthetics induced similar changes during excitation by glutamate."} {"id": "PMID:168357", "title": "The control of adaptive hypertrophy in the salt glands of geese and ducks.", "content": "1. Factors controlling adaptive hypertrophy, which occurs when marine, or potentially marine, birds drink salt water, have been investigated in geese and ducks using changes in salt-weight weight, RNA and DNA contents as indices of this process. 2. Unilateral post-ganglionic denervation in geese prevented the changes in [RNA] and [RNA]:[DNA] that occurred in the intact gland of birds given salt water for 24 hr; denervation had no significant effect in birds on fresh water throughout. 3. Atropine treatment also prevented the adaptive changes in geese given salt water. 4. In ducks give 0.3 M-NaCl for 48 hr salt-gland weight, [RNA] and [RNA]:[DNA] increase markedly. Treatment of ducks drinking fresh water with large doses of corticosterone and mammalian ACTH for 48 hr had no significant effects on salt-gland weight, RNA or DNA; mammalian prolactin treatment for 48 hr significantly raised [RNA]. 5. No changes in the total amount of DNA in the glands were observed in these experiments, thus indicating that hyperplasia does not occur within 48 hr of a bird first drinking salt water. 6. It is concluded that adaptive hypertrophy is controlled by secretory nerves, and that hormones, if they play any part in this process, have a permissive or secondary role. It is suggested that hypertrophy and the maintenance of the secretory cells in the fully-adapted state may be obligatorily related to secretory activity induced by cholinergic secretory nerves.", "contents": "The control of adaptive hypertrophy in the salt glands of geese and ducks. 1. Factors controlling adaptive hypertrophy, which occurs when marine, or potentially marine, birds drink salt water, have been investigated in geese and ducks using changes in salt-weight weight, RNA and DNA contents as indices of this process. 2. Unilateral post-ganglionic denervation in geese prevented the changes in [RNA] and [RNA]:[DNA] that occurred in the intact gland of birds given salt water for 24 hr; denervation had no significant effect in birds on fresh water throughout. 3. Atropine treatment also prevented the adaptive changes in geese given salt water. 4. In ducks give 0.3 M-NaCl for 48 hr salt-gland weight, [RNA] and [RNA]:[DNA] increase markedly. Treatment of ducks drinking fresh water with large doses of corticosterone and mammalian ACTH for 48 hr had no significant effects on salt-gland weight, RNA or DNA; mammalian prolactin treatment for 48 hr significantly raised [RNA]. 5. No changes in the total amount of DNA in the glands were observed in these experiments, thus indicating that hyperplasia does not occur within 48 hr of a bird first drinking salt water. 6. It is concluded that adaptive hypertrophy is controlled by secretory nerves, and that hormones, if they play any part in this process, have a permissive or secondary role. It is suggested that hypertrophy and the maintenance of the secretory cells in the fully-adapted state may be obligatorily related to secretory activity induced by cholinergic secretory nerves."} {"id": "PMID:168358", "title": "Electrophysiological properties of spinal motoneurones of normal and dystrophic mice.", "content": "1. The properties of spinal motoneurones of normal and dystrophic mice (129/ReJ) were examined with intracellular electrodes. 2. The following parameters of spinal motoneurones showed no significant differences between normal and dystrophic mice: resting and action potentials, the amplitude and duration of after-hyperpolarization, rheobasic current for excitation, threshold for excitation of the somadendritic membrane (IS-SD inflexion) and input resistance. 3. The changes in motoneurone properties observed 13-16 days after section of the sciatic nerve (axotomy) were similar in both normal and dystrophic mice. 4. The axonal conduction velocity of motoneurones in dystrophic mice was about ten times slower than that in normal mice. The conduction velocity of the sciatic nerve was only about 25% slower in dystrophic mice than in the normal animal. The estimated ventral root conduction velocity as well as the observed dorsal root conduction velocity in dystrophic mice was at least twenty times slower than that in normal mice. 5. In dystrophic mice, spinal motoneurones often showed multiple discharges in response to single, antidromic stimuli. The site of initiation of multiple discharge was located in the motor axon rather than in the motoneurone cell body. 6. In dystrophic mice, nerve impulses were transmitted from fibre to fibre ('cross-talk'). The site of impulse transmission among nerve fibres was near the distal portion of the spinal roots. 7. Synaptic potentials and peripheral reflex discharges evoked by stimulation of the dorsal roots showed a longer latency and were more prolonged in dystrophic mice than in the control mice. 8. The motoneurone properties of dystrophic mice showed no tendency of progressive changes with age ranging from 63 to 148 days. 9. It is concluded that the properties of motoneurone cell bodies examined in dystrophic mice are indistinguishable from those in normal mice and that the only abnormality in motoneurones of the former residues in the motor axon. 10. It is suggested that integrity of the discharge pattern of spinal motoneurones in dystrophic mice is interfered by anomalous impluse transmission in the motor axons and that the motoneurones in dystrophic mice are a homogeneous group rather than a mixture of \"normal\" and \"abnormal\" neurones.", "contents": "Electrophysiological properties of spinal motoneurones of normal and dystrophic mice. 1. The properties of spinal motoneurones of normal and dystrophic mice (129/ReJ) were examined with intracellular electrodes. 2. The following parameters of spinal motoneurones showed no significant differences between normal and dystrophic mice: resting and action potentials, the amplitude and duration of after-hyperpolarization, rheobasic current for excitation, threshold for excitation of the somadendritic membrane (IS-SD inflexion) and input resistance. 3. The changes in motoneurone properties observed 13-16 days after section of the sciatic nerve (axotomy) were similar in both normal and dystrophic mice. 4. The axonal conduction velocity of motoneurones in dystrophic mice was about ten times slower than that in normal mice. The conduction velocity of the sciatic nerve was only about 25% slower in dystrophic mice than in the normal animal. The estimated ventral root conduction velocity as well as the observed dorsal root conduction velocity in dystrophic mice was at least twenty times slower than that in normal mice. 5. In dystrophic mice, spinal motoneurones often showed multiple discharges in response to single, antidromic stimuli. The site of initiation of multiple discharge was located in the motor axon rather than in the motoneurone cell body. 6. In dystrophic mice, nerve impulses were transmitted from fibre to fibre ('cross-talk'). The site of impulse transmission among nerve fibres was near the distal portion of the spinal roots. 7. Synaptic potentials and peripheral reflex discharges evoked by stimulation of the dorsal roots showed a longer latency and were more prolonged in dystrophic mice than in the control mice. 8. The motoneurone properties of dystrophic mice showed no tendency of progressive changes with age ranging from 63 to 148 days. 9. It is concluded that the properties of motoneurone cell bodies examined in dystrophic mice are indistinguishable from those in normal mice and that the only abnormality in motoneurones of the former residues in the motor axon. 10. It is suggested that integrity of the discharge pattern of spinal motoneurones in dystrophic mice is interfered by anomalous impluse transmission in the motor axons and that the motoneurones in dystrophic mice are a homogeneous group rather than a mixture of \"normal\" and \"abnormal\" neurones."} {"id": "PMID:168359", "title": "Extracellular potassium changes in the spinal cord of the cat and their relation to slow potentials, active transport and impulse transmission.", "content": "1. By means of K-specific double-barrelled micro-electrodes the time course of changes in K+ concentration in the extracellular space of the lumbar spinal cord was examined after peripheral tetanic stimulation and after a single volley in a mixed peripheral nerve in non-anaesthetized, intercollicularly decerebrated and spinalized cats. 2. Tetanic stimulation (100 Hz) which increases the [K]e from 3 to 9 mM is followed by a phase of reduced [K]e during which [K]e decreases by 0.5 mM below resting level, lasting 1-2 minutes before returning to its original resting level. Evidence is presented that this subnormal phase of [K]e reflects active processes redistributing accumulated K+ from extracellular space. 3. The subnormal phase of [K]e can be registered only when the microelectrode is located in very close vicinity of discharging neurones and is not primarily dependent on the absolute level of increased [K]e. This can be considered as evidence that the neurones and not the glial cells are responsible for active reabsorption of K+ from the extracellular space. 4. Increased E1K]e is reflected in focally recorded potentials as a negativity and decreased [K]e as a positivity. The latency of focally recorded positivity is, however, shorter than the latency of reduced [K]e. This makes it likely that the positivity reflects not only passive hyperpolarization of glial elements, but also an active, electrogenic ion transport across neuronal membrane. 5. The shortest latency of increased [K]e induced by a single volley in a mixed peripheral nerve was found to be 9 msec; the peak, representing 0.5 mM, was attained after 40 msec and the total duration was 200 msec. A theoretical consideration is put forward that the time course of transient increase in [K]e is consistent with the suggestion that K+ which accumulates in the spinal cord after neuronal discharge is responsible for primary afferent depolarization. 6. Evidence is presented that increased [K]e, induced by a long lasting peripheral stimulation, is accompanied by decreased efficacy of impulse transmission.", "contents": "Extracellular potassium changes in the spinal cord of the cat and their relation to slow potentials, active transport and impulse transmission. 1. By means of K-specific double-barrelled micro-electrodes the time course of changes in K+ concentration in the extracellular space of the lumbar spinal cord was examined after peripheral tetanic stimulation and after a single volley in a mixed peripheral nerve in non-anaesthetized, intercollicularly decerebrated and spinalized cats. 2. Tetanic stimulation (100 Hz) which increases the [K]e from 3 to 9 mM is followed by a phase of reduced [K]e during which [K]e decreases by 0.5 mM below resting level, lasting 1-2 minutes before returning to its original resting level. Evidence is presented that this subnormal phase of [K]e reflects active processes redistributing accumulated K+ from extracellular space. 3. The subnormal phase of [K]e can be registered only when the microelectrode is located in very close vicinity of discharging neurones and is not primarily dependent on the absolute level of increased [K]e. This can be considered as evidence that the neurones and not the glial cells are responsible for active reabsorption of K+ from the extracellular space. 4. Increased E1K]e is reflected in focally recorded potentials as a negativity and decreased [K]e as a positivity. The latency of focally recorded positivity is, however, shorter than the latency of reduced [K]e. This makes it likely that the positivity reflects not only passive hyperpolarization of glial elements, but also an active, electrogenic ion transport across neuronal membrane. 5. The shortest latency of increased [K]e induced by a single volley in a mixed peripheral nerve was found to be 9 msec; the peak, representing 0.5 mM, was attained after 40 msec and the total duration was 200 msec. A theoretical consideration is put forward that the time course of transient increase in [K]e is consistent with the suggestion that K+ which accumulates in the spinal cord after neuronal discharge is responsible for primary afferent depolarization. 6. Evidence is presented that increased [K]e, induced by a long lasting peripheral stimulation, is accompanied by decreased efficacy of impulse transmission."} {"id": "PMID:168363", "title": "Depression in the excitability of relay cells of lateral geniculate nucleus following saccadic eye movements in the cat.", "content": "1. The excitability of relay cells of the lateral geniculate nucleus during a saccadic eye movement was studied in alert cats. Excitability was assessed by the firing probability of the cells in response to electrical stimulation of the optic chiasm. Modifications in the excitability were evaluated during the period following eye movements, by triggering a stimulator from potential shifts in electro-oculogram and altering delays in the stimulus pulse. 2. The cells were classified into S and T cells, based on their response properties and the latencies to chiasmatic stimulation. With a saccade in a stationary patterned field, T cells showed a burst discharge, while the discharges of S cells were completely suppressed. 3. The excitability was depressed in both S and T cells for 150-200 msec after a saccade, when the eye movement occurred in light. However, the depression did not occur in complete darkness. 4. The depression occurred also in the absence of eye movement, when the patterned visual field was moved in a saccadic fashion. 5. The depression in S cells occurred during an inhibitory period. Since S cells do not receive signals on image movement directly from the retina, the depression was due to a recurrent inhibition by signals transferred through the T ganglion-relay cell channel. 6. The depression in T cells occurred concomitantly with the burst discharge. Since the recurrent inhibition was operating less effectively during the period, the depression may be due to a phasic occlusion of the test impulse by coincident high-rate firings in the same cell. 7. The impairment in transmission of visual information through the lateral geniculate nucleus during the period following eye movements has been discussed in connexion with a neurophysiological basis for saccadic suppression.", "contents": "Depression in the excitability of relay cells of lateral geniculate nucleus following saccadic eye movements in the cat. 1. The excitability of relay cells of the lateral geniculate nucleus during a saccadic eye movement was studied in alert cats. Excitability was assessed by the firing probability of the cells in response to electrical stimulation of the optic chiasm. Modifications in the excitability were evaluated during the period following eye movements, by triggering a stimulator from potential shifts in electro-oculogram and altering delays in the stimulus pulse. 2. The cells were classified into S and T cells, based on their response properties and the latencies to chiasmatic stimulation. With a saccade in a stationary patterned field, T cells showed a burst discharge, while the discharges of S cells were completely suppressed. 3. The excitability was depressed in both S and T cells for 150-200 msec after a saccade, when the eye movement occurred in light. However, the depression did not occur in complete darkness. 4. The depression occurred also in the absence of eye movement, when the patterned visual field was moved in a saccadic fashion. 5. The depression in S cells occurred during an inhibitory period. Since S cells do not receive signals on image movement directly from the retina, the depression was due to a recurrent inhibition by signals transferred through the T ganglion-relay cell channel. 6. The depression in T cells occurred concomitantly with the burst discharge. Since the recurrent inhibition was operating less effectively during the period, the depression may be due to a phasic occlusion of the test impulse by coincident high-rate firings in the same cell. 7. The impairment in transmission of visual information through the lateral geniculate nucleus during the period following eye movements has been discussed in connexion with a neurophysiological basis for saccadic suppression."} {"id": "PMID:168366", "title": "Five seasons of sadness.", "content": "In response to her grandmother's death, moving back to her family, and beginning kindergarten, Bridget experienced a very difficult adjustment. During the period of play therapy, she began grief work: \"Emancipation from bondage to the deceased, readjustment ot the environment in which the deceased is missing, and formation of new relationships.\"15 Bridget, at the age of five, has experienced five seasons of sadness. Yet her quiet and determined strength has enabled her to readjust to her once threatening environment. The therapist suggested continued therapy in the school environment to aid Bridget in formation of new relationships. The shadow of Bridget's five seasons of sadness seems to have lifted. Her bright affect and look of expectancy seem to be asking of the other children: \"Will you be my friend? For no reason that I know Except I want you so.\"16", "contents": "Five seasons of sadness. In response to her grandmother's death, moving back to her family, and beginning kindergarten, Bridget experienced a very difficult adjustment. During the period of play therapy, she began grief work: \"Emancipation from bondage to the deceased, readjustment ot the environment in which the deceased is missing, and formation of new relationships.\"15 Bridget, at the age of five, has experienced five seasons of sadness. Yet her quiet and determined strength has enabled her to readjust to her once threatening environment. The therapist suggested continued therapy in the school environment to aid Bridget in formation of new relationships. The shadow of Bridget's five seasons of sadness seems to have lifted. Her bright affect and look of expectancy seem to be asking of the other children: \"Will you be my friend? For no reason that I know Except I want you so.\"16"} {"id": "PMID:168367", "title": "Assuring accountability for the poor: patient advocates.", "content": "The three patient advocate groups that existed in this particular state hospital and differing structures, functions and degrees of effectiveness. However, all three seemed necessary to assure that the serving institution and its professionals would become accountable for the success or failure of their methods and performance. Two of the groups (relatives group and legal aid group) seemed to be functioning effectively within certain limits which each thought to be appropriate in advocating patient causes. Thus, they were providing the countervailing force that is a necessary component of accountability when the persons to be served are a powerless group. The consumer group being the powerless group was not effective in advocating its own cause. It would have been very beneficial to this group had they succeeded. There is a therapeutic effect of having control over one's own life that fosters independence and decreases withdrawal and feelings of alienation from the social order. Certainly these are the goals of the mental health professionals for their patients. In order to realize these goals certain changes would have to be made in the mental health code would have to be changed to include formalized grievance procedures and the desirability of consumer groups would have to be formally established. If this were so, consumers of mental health services might be more effective in advocating their own causes and would be more able to hold the serving institution accountable", "contents": "Assuring accountability for the poor: patient advocates. The three patient advocate groups that existed in this particular state hospital and differing structures, functions and degrees of effectiveness. However, all three seemed necessary to assure that the serving institution and its professionals would become accountable for the success or failure of their methods and performance. Two of the groups (relatives group and legal aid group) seemed to be functioning effectively within certain limits which each thought to be appropriate in advocating patient causes. Thus, they were providing the countervailing force that is a necessary component of accountability when the persons to be served are a powerless group. The consumer group being the powerless group was not effective in advocating its own cause. It would have been very beneficial to this group had they succeeded. There is a therapeutic effect of having control over one's own life that fosters independence and decreases withdrawal and feelings of alienation from the social order. Certainly these are the goals of the mental health professionals for their patients. In order to realize these goals certain changes would have to be made in the mental health code would have to be changed to include formalized grievance procedures and the desirability of consumer groups would have to be formally established. If this were so, consumers of mental health services might be more effective in advocating their own causes and would be more able to hold the serving institution accountable"} {"id": "PMID:168375", "title": "[A case of carcinoma of the stomach with calcification (author's transl)].", "content": "The authors found only 25 cases of calcified carcinoma of the stomach in the literature. The course in this case was rapidly fatal. Calcification within the tumour infiltrates the gastric wall and has a very characteristic miliary appearance, permitting one to make the diagnosis on a straight X-Ray of the abdomen. The mechanism of precipitation of calcium within certain mucus-secreting carcinomas has not been determined. Various theories are suggested.", "contents": "[A case of carcinoma of the stomach with calcification (author's transl)]. The authors found only 25 cases of calcified carcinoma of the stomach in the literature. The course in this case was rapidly fatal. Calcification within the tumour infiltrates the gastric wall and has a very characteristic miliary appearance, permitting one to make the diagnosis on a straight X-Ray of the abdomen. The mechanism of precipitation of calcium within certain mucus-secreting carcinomas has not been determined. Various theories are suggested."} {"id": "PMID:168376", "title": "Clinical diagnosis of breast cancer.", "content": "Breast cancer is the most common malignant neoplasm in women, and 6% will develop it during their normal life expectancy. There is a group who have a high risk of developing breast cancer. The recent improvement in cure rates seems to be jue chiefly to earlier diagnosis rather than to improved methods of therapy. The physician, by careful periodic breast examinations and by the judicious use of diagnostic aids such as mammography and thermography, especially in the high risk group, has a golden opportunity to pick up cancer in a localized stage where the prognosis for cure with appropriate therapy is excellent. A tentative diagnosis of breast cancer (Table XI) can be made with a fair degree of accuracy by taking a careful history, utilizing and combining available statistics about the frequency, median age, characteristic symptom complexes of the common breast lesions and factors related to a high mammary carcinoma risk, and by a systematic and thorough breast examination supplemented with diagnostic aids when appropriate. However, biopsy and histologic examination is mandatory in all patients with a) true, three dimentional, dominant lumps even if diagnostic aids are negative except for cysts which can be safely aspirated under controlled conditions; b) suspicious lesions found by diagnostic aids even though there are no clinical findings; c) serous, serosanguineous, bloody, or watery nipple discharge; and d) other signs of cancer, i.e. eczema of the nipple, axillary adenopathy, etc., in order to determine with absolute accuracy whether the lesion is benign or malignant.", "contents": "Clinical diagnosis of breast cancer. Breast cancer is the most common malignant neoplasm in women, and 6% will develop it during their normal life expectancy. There is a group who have a high risk of developing breast cancer. The recent improvement in cure rates seems to be jue chiefly to earlier diagnosis rather than to improved methods of therapy. The physician, by careful periodic breast examinations and by the judicious use of diagnostic aids such as mammography and thermography, especially in the high risk group, has a golden opportunity to pick up cancer in a localized stage where the prognosis for cure with appropriate therapy is excellent. A tentative diagnosis of breast cancer (Table XI) can be made with a fair degree of accuracy by taking a careful history, utilizing and combining available statistics about the frequency, median age, characteristic symptom complexes of the common breast lesions and factors related to a high mammary carcinoma risk, and by a systematic and thorough breast examination supplemented with diagnostic aids when appropriate. However, biopsy and histologic examination is mandatory in all patients with a) true, three dimentional, dominant lumps even if diagnostic aids are negative except for cysts which can be safely aspirated under controlled conditions; b) suspicious lesions found by diagnostic aids even though there are no clinical findings; c) serous, serosanguineous, bloody, or watery nipple discharge; and d) other signs of cancer, i.e. eczema of the nipple, axillary adenopathy, etc., in order to determine with absolute accuracy whether the lesion is benign or malignant."} {"id": "PMID:168374", "title": "A systems analysis approach to planned change in a clinical psychiatric program.", "content": "In health car facilities, systems studies are commonly conducted as ivory-tower operations with minimal impact and little practical result. A real-life case study was presented to demonstrate how it can be used effectively in a collaborative manner to implement constructive change. Systems Analysis techniques were succe-sfully used with the staff of a psychiatric ward to plan for a satellite outpatient treatment program. The focus was on collaboration to help the ward to obtain objective information for decisions concerning the need for changes in their existing system.", "contents": "A systems analysis approach to planned change in a clinical psychiatric program. In health car facilities, systems studies are commonly conducted as ivory-tower operations with minimal impact and little practical result. A real-life case study was presented to demonstrate how it can be used effectively in a collaborative manner to implement constructive change. Systems Analysis techniques were succe-sfully used with the staff of a psychiatric ward to plan for a satellite outpatient treatment program. The focus was on collaboration to help the ward to obtain objective information for decisions concerning the need for changes in their existing system."} {"id": "PMID:168380", "title": "Adenosine cyclic 3',5',-monophosphate phosphodiesterasr inhibitors. 2.3-Substituted 5,7-dialkylpyrazolo [1,5-a]pyrimidines.", "content": "A number of 3-bromo-, 3-nitro-, and 3-ethoxycarbonyl-5,7-dialkylpyrazolo[1,5-a]pyrimidines were synthesized and screened as in vitro cAMP phosphodiesterase inhibitors. The condensation of 3-aminopyrazole with symmetrical beta-diketones (acetylacetone, heptane-3,5-dione, etc.) afforded symmetrical dialkylpyrazolo[1,5-a]pyrimidines (5). The reaction of 3-aminopyrazole with unsymmetrical beta-diketones (hexane-2,4-dione, heptane-3,5-dione, etc.) gave a mixture of 5-methyl-7-alkylpyrazolo[1,5-a]pyrimidine (3) and 5-alkyl-7-methylpyrazolo[1,5-a]pyrimidines (4). The technique for the separation of 3 from 4 is described. The inhibition constants, alpha (the ratio of the molar I50 of theophylline to the molar I50 of the test compounds), were subjected to a Hansch correlation analysis. The results indicated that PDE isolated from beef heart tissue was most sensitive to changes in the length of the alkyl group in the 5 position of the pyrazolo[1,5-a]pyrimidine ring, whereas the PDE isolated from rabbit lung tissue was more sensitive to changes in the length of the 7-alkyl group. Experimentally and theoretically, the n-propyl group was found to approximate the ideal size for the alkyl group in both the 5 and 7 positions;5,7-di-n-propyl-3-ethoxycarbonylpyrazolo[1,5-a]pyrimidine (5e) was the most potent inhibitor of both lung and heart PDE.", "contents": "Adenosine cyclic 3',5',-monophosphate phosphodiesterasr inhibitors. 2.3-Substituted 5,7-dialkylpyrazolo [1,5-a]pyrimidines. A number of 3-bromo-, 3-nitro-, and 3-ethoxycarbonyl-5,7-dialkylpyrazolo[1,5-a]pyrimidines were synthesized and screened as in vitro cAMP phosphodiesterase inhibitors. The condensation of 3-aminopyrazole with symmetrical beta-diketones (acetylacetone, heptane-3,5-dione, etc.) afforded symmetrical dialkylpyrazolo[1,5-a]pyrimidines (5). The reaction of 3-aminopyrazole with unsymmetrical beta-diketones (hexane-2,4-dione, heptane-3,5-dione, etc.) gave a mixture of 5-methyl-7-alkylpyrazolo[1,5-a]pyrimidine (3) and 5-alkyl-7-methylpyrazolo[1,5-a]pyrimidines (4). The technique for the separation of 3 from 4 is described. The inhibition constants, alpha (the ratio of the molar I50 of theophylline to the molar I50 of the test compounds), were subjected to a Hansch correlation analysis. The results indicated that PDE isolated from beef heart tissue was most sensitive to changes in the length of the alkyl group in the 5 position of the pyrazolo[1,5-a]pyrimidine ring, whereas the PDE isolated from rabbit lung tissue was more sensitive to changes in the length of the 7-alkyl group. Experimentally and theoretically, the n-propyl group was found to approximate the ideal size for the alkyl group in both the 5 and 7 positions;5,7-di-n-propyl-3-ethoxycarbonylpyrazolo[1,5-a]pyrimidine (5e) was the most potent inhibitor of both lung and heart PDE."} {"id": "PMID:168381", "title": "Synthesis and antitumor activity of 5'-phosphates and cyclic 3',5'-phosphates derived from biologically active nucleosides.", "content": "Syntheses and biological activities of 12 N6-substituted adenosine 5'-phosphates and 15 cyclic 3',5'-phosphates are described. Included among these are the cyclic phosphates of the naturally occurring anticodon adjacent modified nucleosides, N6-(delta2-isopentenyl)adenosine and N-(purin-6-ylcarbamoyl)-L-threonine ribonucleoside. Also reported in this paper are the 5'-phosphates and cyclic phosphates of the cytokinins, N6-benzyladenosine, kinetin ribonucleoside, 3-(chloro-trans-2-buten-2-yl)adenosine,6-o-chlorophenylureidopurine ribonucleoside, and 6-allylureidopurine ribonucleoside. The 5'-nucleotides were prepared by direct phosphorylation of the corresponding ribonucleosides with POCl3 and triethyl phosphate. These compounds were converted to the cyclic 3',5'-phosphates by cyclization of the corresponding 5'-nucleotides with dicyclohexylcarbodiimide. Comparison of the cytotoxicity of the ribonucleosides with their 5'-nucleotides and cyclic 3',5'-nucleotides showed that some of the 5'-phosphates and cyclic phosphates were almost as active as the parent nucleosides. The 5'-nucleotides and the cyclic phosphates were more soluble than the parent nucleosides. The cyclic 3',5'-nucleotides were examined as alternate activators of cAMP-dependent protein kinase from beef heart. While all of the analogs studied showed some activity toward this enzyme, several compounds were more effective than cAMP itself. The analogs were also tested as substrates for cyclic 3',5'-nucleotide phosphodiesterase from beef heart. The N6-alkyl-cAMP analogs were poor substrates for the enzyme, while N6-carbamoyl-cAMP derivatives were inert toward this enzyme. These compounds did not inhibit the phosphodiesterase. Some of the cyclic phosphates exhibited marginal effect in the inhibition of glycogen synthesis in skin slices.", "contents": "Synthesis and antitumor activity of 5'-phosphates and cyclic 3',5'-phosphates derived from biologically active nucleosides. Syntheses and biological activities of 12 N6-substituted adenosine 5'-phosphates and 15 cyclic 3',5'-phosphates are described. Included among these are the cyclic phosphates of the naturally occurring anticodon adjacent modified nucleosides, N6-(delta2-isopentenyl)adenosine and N-(purin-6-ylcarbamoyl)-L-threonine ribonucleoside. Also reported in this paper are the 5'-phosphates and cyclic phosphates of the cytokinins, N6-benzyladenosine, kinetin ribonucleoside, 3-(chloro-trans-2-buten-2-yl)adenosine,6-o-chlorophenylureidopurine ribonucleoside, and 6-allylureidopurine ribonucleoside. The 5'-nucleotides were prepared by direct phosphorylation of the corresponding ribonucleosides with POCl3 and triethyl phosphate. These compounds were converted to the cyclic 3',5'-phosphates by cyclization of the corresponding 5'-nucleotides with dicyclohexylcarbodiimide. Comparison of the cytotoxicity of the ribonucleosides with their 5'-nucleotides and cyclic 3',5'-nucleotides showed that some of the 5'-phosphates and cyclic phosphates were almost as active as the parent nucleosides. The 5'-nucleotides and the cyclic phosphates were more soluble than the parent nucleosides. The cyclic 3',5'-nucleotides were examined as alternate activators of cAMP-dependent protein kinase from beef heart. While all of the analogs studied showed some activity toward this enzyme, several compounds were more effective than cAMP itself. The analogs were also tested as substrates for cyclic 3',5'-nucleotide phosphodiesterase from beef heart. The N6-alkyl-cAMP analogs were poor substrates for the enzyme, while N6-carbamoyl-cAMP derivatives were inert toward this enzyme. These compounds did not inhibit the phosphodiesterase. Some of the cyclic phosphates exhibited marginal effect in the inhibition of glycogen synthesis in skin slices."} {"id": "PMID:168382", "title": "Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene (\"1,3-dideazauridine\").", "content": "In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.", "contents": "Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene (\"1,3-dideazauridine\"). In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro."} {"id": "PMID:168383", "title": "Probiotics. Antistaphylococcal and antifibrinolytic activities of omega-amino-and omega-guanidinoalkanisulfonic acids.", "content": "A series of omega-aminoalkanesulfonic acids (1-5) and omega-guanidinoalkanesulfonic acids (6-9) has been tested for antistaphylococcal and antifibrinolytic activities. Most of the omega-aminoalkanesulfonic acids and 6 produced better protection against Staphylococcus aureus infections in mice than gamma-aminobutyryl-L-histidine. Compound 4 was the best antistaphylococcal agent among the omega-aminoalkanesulfonic acids and compound 6 among the omega-guanidinoalkanesulfonic acids. Most of the omega-aminoalkanesulfonic acids have antifibrinolytic activity, while none of the omega-guanidinoalkanesulfonic acids has significant antifibrinolytic activity. Compound 4 possessed the highest antifibrinolytic activity which was equal to or greater than that of epsilon-aminohexanoic acid.", "contents": "Probiotics. Antistaphylococcal and antifibrinolytic activities of omega-amino-and omega-guanidinoalkanisulfonic acids. A series of omega-aminoalkanesulfonic acids (1-5) and omega-guanidinoalkanesulfonic acids (6-9) has been tested for antistaphylococcal and antifibrinolytic activities. Most of the omega-aminoalkanesulfonic acids and 6 produced better protection against Staphylococcus aureus infections in mice than gamma-aminobutyryl-L-histidine. Compound 4 was the best antistaphylococcal agent among the omega-aminoalkanesulfonic acids and compound 6 among the omega-guanidinoalkanesulfonic acids. Most of the omega-aminoalkanesulfonic acids have antifibrinolytic activity, while none of the omega-guanidinoalkanesulfonic acids has significant antifibrinolytic activity. Compound 4 possessed the highest antifibrinolytic activity which was equal to or greater than that of epsilon-aminohexanoic acid."} {"id": "PMID:168384", "title": "Synthesis and biological activity of some 8-substituted selenoguanosine cyclic 3',5'-phosphates and related compounds.", "content": "8-Bromoguanosine cyclic 3',5'-monophosphate, 8-bromoguanosine 5'-monophosphate, and 8-bromoguanosine served as intermediates for the chemical synthesis of a series of 8-substituted seleno cyclic nucleotides, nucleotides, and their nucleosides. Selenourea was found to be a useful reagent in synthesizing these seleno-substituted nucleoside, nucleotide, and cyclic nucleotide. A nucleic acid analyzer was used to study the hydrolysis of these cyclic nucleotides by phosphodiesterase. It was found that all of the 8-substituted selenoguanosine cyclic 3',5'-phosphates synthesized, except 8-MeSe-cGMP, were resistant to hydrolyze by phosphodiesterase. These 8-substituted seleno cyclic GMP derivatives showed some antitumor activities against murine leukemic cells (L5178Y) in vitro and in vivo.", "contents": "Synthesis and biological activity of some 8-substituted selenoguanosine cyclic 3',5'-phosphates and related compounds. 8-Bromoguanosine cyclic 3',5'-monophosphate, 8-bromoguanosine 5'-monophosphate, and 8-bromoguanosine served as intermediates for the chemical synthesis of a series of 8-substituted seleno cyclic nucleotides, nucleotides, and their nucleosides. Selenourea was found to be a useful reagent in synthesizing these seleno-substituted nucleoside, nucleotide, and cyclic nucleotide. A nucleic acid analyzer was used to study the hydrolysis of these cyclic nucleotides by phosphodiesterase. It was found that all of the 8-substituted selenoguanosine cyclic 3',5'-phosphates synthesized, except 8-MeSe-cGMP, were resistant to hydrolyze by phosphodiesterase. These 8-substituted seleno cyclic GMP derivatives showed some antitumor activities against murine leukemic cells (L5178Y) in vitro and in vivo."} {"id": "PMID:168385", "title": "Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone.", "content": "The synthesis of 4'-epi-daunorubicin and of 4'-epi-adriamycin was performed by condensation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride with daunomycinone or the protected adriamycinone derivative 17, respectively. Both the alpha and beta anomers were obtained and characterized. All new compounds are biologically active in cultured cells and the alpha anomers display noticeable activity in experimental tumors in mice. Interestingly, 4'-epi-adriamycin (4) appears nontoxic to cultured heart cells up to a concentration of 5 mug/ml.", "contents": "Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone. The synthesis of 4'-epi-daunorubicin and of 4'-epi-adriamycin was performed by condensation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride with daunomycinone or the protected adriamycinone derivative 17, respectively. Both the alpha and beta anomers were obtained and characterized. All new compounds are biologically active in cultured cells and the alpha anomers display noticeable activity in experimental tumors in mice. Interestingly, 4'-epi-adriamycin (4) appears nontoxic to cultured heart cells up to a concentration of 5 mug/ml."} {"id": "PMID:168399", "title": "Effect of 2-deoxy-D-glucose on herpesvirus-induced inhibition of cellular DNA synthesis.", "content": "In pseudorabies virus-infected cells host DNA synthesis is turned off 4 to 5 h postinfection. In the presence of 0.5 mM 2-deoxy-D-glucose, however, synthesis of both cellular and viral DNA proceeds unimpaired throughout the virus replication cycle. The uptake of radioactive thymidine into mock-infected cells is not altered in the presence of 2-deoxy-D-glucose. Virus-specific protein synthesis and particle formation also proceed in medium containing the deoxy sugar, but the virus particles produced are noninfectious and cell fusion is inhibited.", "contents": "Effect of 2-deoxy-D-glucose on herpesvirus-induced inhibition of cellular DNA synthesis. In pseudorabies virus-infected cells host DNA synthesis is turned off 4 to 5 h postinfection. In the presence of 0.5 mM 2-deoxy-D-glucose, however, synthesis of both cellular and viral DNA proceeds unimpaired throughout the virus replication cycle. The uptake of radioactive thymidine into mock-infected cells is not altered in the presence of 2-deoxy-D-glucose. Virus-specific protein synthesis and particle formation also proceed in medium containing the deoxy sugar, but the virus particles produced are noninfectious and cell fusion is inhibited."} {"id": "PMID:168400", "title": "Association of vesicular stomatitis virus glycoprotein with virion membrane: characterization of the lipophilic tail fragment.", "content": "The proteolytic enzyme, thermolysin, degraded the external segment of the membrane glycoprotein of intact vesicular stomatitis (VS) virions but left behind a small nonglycosylated fragment, presumably embedded in the virion membrane. Other proteases generated membrane-associated glycoprotein fragments differing somewhat in molecular weight. The thermolysin-resistant, virion-associated fragment, which can be selectively solubilized by either Triton X-100 or chloroform/methanol, has a molecular weight of 5,200. Amino acid analysis of the glycoprotein fragment reveals a preponderance of hydrophobic amino acids (64% of the residues); the amino-terminal amino acid is alanine as determined by dansylation. Cyanogen bromide digestion of the tail fragment generated two peptides, confirming the presence of one methionine residue per thermolysin-resistant glycoprotein fragment. The secondary structure of this glycoprotein tail peptide is maintained by at least one disulfide bridge. Thermolysin treatment is isolated VS viral glycoprotein in the presence of Triton X-100 also generated a hydrophobic peptide fragment which is very similar to the virion-associated glycoprotein fragment. The amino acid terminus of intact glycoprotein was also found to be alanine as was its dansylated Triton-micellar fragment that resisted thermolytic degradation; this finding suggests that the amino-terminal end of the VS viral glycoprotein is embedded in the virion membrane. These results suggest that the VS viral glycoprotein is an amphipathic molecule, the hydrophilic portion of which contains all the carbohydrate and a lipophilic tail segment which forms lipid or detergent micelles, thus rendering it resistant to proteolysis.", "contents": "Association of vesicular stomatitis virus glycoprotein with virion membrane: characterization of the lipophilic tail fragment. The proteolytic enzyme, thermolysin, degraded the external segment of the membrane glycoprotein of intact vesicular stomatitis (VS) virions but left behind a small nonglycosylated fragment, presumably embedded in the virion membrane. Other proteases generated membrane-associated glycoprotein fragments differing somewhat in molecular weight. The thermolysin-resistant, virion-associated fragment, which can be selectively solubilized by either Triton X-100 or chloroform/methanol, has a molecular weight of 5,200. Amino acid analysis of the glycoprotein fragment reveals a preponderance of hydrophobic amino acids (64% of the residues); the amino-terminal amino acid is alanine as determined by dansylation. Cyanogen bromide digestion of the tail fragment generated two peptides, confirming the presence of one methionine residue per thermolysin-resistant glycoprotein fragment. The secondary structure of this glycoprotein tail peptide is maintained by at least one disulfide bridge. Thermolysin treatment is isolated VS viral glycoprotein in the presence of Triton X-100 also generated a hydrophobic peptide fragment which is very similar to the virion-associated glycoprotein fragment. The amino acid terminus of intact glycoprotein was also found to be alanine as was its dansylated Triton-micellar fragment that resisted thermolytic degradation; this finding suggests that the amino-terminal end of the VS viral glycoprotein is embedded in the virion membrane. These results suggest that the VS viral glycoprotein is an amphipathic molecule, the hydrophilic portion of which contains all the carbohydrate and a lipophilic tail segment which forms lipid or detergent micelles, thus rendering it resistant to proteolysis."} {"id": "PMID:168401", "title": "Intracellular synthesis of mouse mammary tumor virus polypeptides: indication of a precursor glycoprotein.", "content": "Mouse mammary tumor virus polypeptides were detected in the cytoplasm of mouse mammary tumor cell cultures using immunological precipitation techniques. The anti-mouse mammary tumor virus serum precipitated the major virion glycoproteins gp49 and gp37.5/33.5 and a viral-related nonvirion glycoprotein of 76,000 daltons. Subcellular fractionation studies revelaed that the cell-associated virion glycoproteins were present in the membrane fraction. Pulsechase experiments indicated that a viral-related nonvirion glycoprotein of 76,000 daltons may be a precursor to one or more of the virion glycoproteins.", "contents": "Intracellular synthesis of mouse mammary tumor virus polypeptides: indication of a precursor glycoprotein. Mouse mammary tumor virus polypeptides were detected in the cytoplasm of mouse mammary tumor cell cultures using immunological precipitation techniques. The anti-mouse mammary tumor virus serum precipitated the major virion glycoproteins gp49 and gp37.5/33.5 and a viral-related nonvirion glycoprotein of 76,000 daltons. Subcellular fractionation studies revelaed that the cell-associated virion glycoproteins were present in the membrane fraction. Pulsechase experiments indicated that a viral-related nonvirion glycoprotein of 76,000 daltons may be a precursor to one or more of the virion glycoproteins."} {"id": "PMID:168402", "title": "Temperature-sensitive mutants of herpes simplex virus type 1 defective in lysis but not in transformation.", "content": "Twelve temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1), representing seven complementation groups, were isolated subsequent to 5-bromodeoxyuridine mutagenesis. These mutants were identified by their inability to replicate in a line of monkey (CV-1) cells at 39 C. Seven of these mutants, representing six complementation groups, induced thymidine kinase (tk) and transformed Ltk- cells, a line of mouse L cells lacking tk, to a tk+ phenotype at both the permissive (34 C) and nonpermissive (39 C) temperatures. Thus, the defective cistrons in these six complementation groups, although necessary for lysis, have no essential function in this transformation system. Transformation by these 12 mutants was dependent on prior UV irradiation. Infection of cells with unirradiated virus under conditions which did not permit virus replication was not sufficient to allow cell transformation. Five mutants, representing two complementation groups, were tk- and were incapable of causing the tk--to-tk+ transformation at either 34 C of 39 C. The tk defects in these mutants are probably unrelated to the ts defects, since one of these complementation groups contains a tk+ member. Therefore, transformation of Ltk- cells to a tk+ phenotype by HSV-1 requires an active viral tk gene. One complementation group was represented by a single tk- member. The role of this cistron in transformation remains undetermined since the primary block to transformation is presumed to be the tk- phenotype. Mutants representing the seven complementation groups were unable to replicate at 39 C in two lines of HSV-1-transformed cells, indicating that the activities of resident wild-type copies of the defective cistrons, if present, could not be detected by complementation.", "contents": "Temperature-sensitive mutants of herpes simplex virus type 1 defective in lysis but not in transformation. Twelve temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1), representing seven complementation groups, were isolated subsequent to 5-bromodeoxyuridine mutagenesis. These mutants were identified by their inability to replicate in a line of monkey (CV-1) cells at 39 C. Seven of these mutants, representing six complementation groups, induced thymidine kinase (tk) and transformed Ltk- cells, a line of mouse L cells lacking tk, to a tk+ phenotype at both the permissive (34 C) and nonpermissive (39 C) temperatures. Thus, the defective cistrons in these six complementation groups, although necessary for lysis, have no essential function in this transformation system. Transformation by these 12 mutants was dependent on prior UV irradiation. Infection of cells with unirradiated virus under conditions which did not permit virus replication was not sufficient to allow cell transformation. Five mutants, representing two complementation groups, were tk- and were incapable of causing the tk--to-tk+ transformation at either 34 C of 39 C. The tk defects in these mutants are probably unrelated to the ts defects, since one of these complementation groups contains a tk+ member. Therefore, transformation of Ltk- cells to a tk+ phenotype by HSV-1 requires an active viral tk gene. One complementation group was represented by a single tk- member. The role of this cistron in transformation remains undetermined since the primary block to transformation is presumed to be the tk- phenotype. Mutants representing the seven complementation groups were unable to replicate at 39 C in two lines of HSV-1-transformed cells, indicating that the activities of resident wild-type copies of the defective cistrons, if present, could not be detected by complementation."} {"id": "PMID:168403", "title": "Reaction of poliovirus RNAs with antibodies to double-stranded RNA demonstrated by an immunochemical binding assay.", "content": "An immunochemical binding assay was used to investigate the reactivity of radioactively labeled viral RNAs from poliovirus-infected cells with antibodies to the synthetic double-stranded RNA, poly(I)-poly(C). A RNase-free antibody-containing serum fraction was employed. Poliovirus replicative form reacted with the antibodies to poly(I)-poly(C) as well as or better than poly(I)-poly(C). Poliovirus replicative intermediate reacted with the antibodies to a greater extent than poliovirus single-stranded RNA, but both were less reactive than replicative form. The use of the immunochemical binding assay with sucrose-gradient fractions demonstrated that for both poliovirus single-stranded RNA and replicative form the peak of reactivity with the antibodies was coincident with the peak of radioactive material precipitated by trichloroacetic acid. The proportion of replicative intermediate that reacted with the antibody increased in sucrose-gradient fractions containing the more slowly sedimenting RI RNA.", "contents": "Reaction of poliovirus RNAs with antibodies to double-stranded RNA demonstrated by an immunochemical binding assay. An immunochemical binding assay was used to investigate the reactivity of radioactively labeled viral RNAs from poliovirus-infected cells with antibodies to the synthetic double-stranded RNA, poly(I)-poly(C). A RNase-free antibody-containing serum fraction was employed. Poliovirus replicative form reacted with the antibodies to poly(I)-poly(C) as well as or better than poly(I)-poly(C). Poliovirus replicative intermediate reacted with the antibodies to a greater extent than poliovirus single-stranded RNA, but both were less reactive than replicative form. The use of the immunochemical binding assay with sucrose-gradient fractions demonstrated that for both poliovirus single-stranded RNA and replicative form the peak of reactivity with the antibodies was coincident with the peak of radioactive material precipitated by trichloroacetic acid. The proportion of replicative intermediate that reacted with the antibody increased in sucrose-gradient fractions containing the more slowly sedimenting RI RNA."} {"id": "PMID:168404", "title": "Human cytomegalovirus. III. Virus-induced DNA polymerase.", "content": "Infection of WI-38 human fibroblasts with human cytomegalovirus (CMV) led to the stimulation of host cell DNA polymerase synthesis and induction of a novel virus-specific DNA polymerase. This cytomegalovirus-induced DNA polymerase was purified and separated from host cell enzymes by DEAE-cellulose and phosphocellulose column chromatographies. It can be distinguished from host cell enzymes by chromatographic behavior, template primer specificity, sedimentation property, and the requirement of salt for maximal activity. This virus-induced enzyme has a sedimentation coefficient of 9.2S and is found in both the nuclei and cytoplasm of virus-infected cells, but not in uninfected cells. This enzyme could efficiently use activated calf-thymus DNA, oly(dA)-oligo(dT)12-18, and poly(dC)-oligo(dG)12-18 as template primers, especially poly(dA)-oligo(dT)12-18, but it could not use poly(rA)-oligo(dT)12-18, poly(rC)-oligo(dG)12-18, or oligo(dT)12-18. The enzyme requires Mg2+ for maximal activity, is sensitive to p-hydroxymercuribenzoate, and is not a zinc metalloenzyme. In addition, the cytomegalovirus-induced DNA polymerase activity can be enhanced by adding 0.06 to 0.12 M NaCl or 0.03 to 0.06 M (NH4)2SO4 to the reaction mixture.", "contents": "Human cytomegalovirus. III. Virus-induced DNA polymerase. Infection of WI-38 human fibroblasts with human cytomegalovirus (CMV) led to the stimulation of host cell DNA polymerase synthesis and induction of a novel virus-specific DNA polymerase. This cytomegalovirus-induced DNA polymerase was purified and separated from host cell enzymes by DEAE-cellulose and phosphocellulose column chromatographies. It can be distinguished from host cell enzymes by chromatographic behavior, template primer specificity, sedimentation property, and the requirement of salt for maximal activity. This virus-induced enzyme has a sedimentation coefficient of 9.2S and is found in both the nuclei and cytoplasm of virus-infected cells, but not in uninfected cells. This enzyme could efficiently use activated calf-thymus DNA, oly(dA)-oligo(dT)12-18, and poly(dC)-oligo(dG)12-18 as template primers, especially poly(dA)-oligo(dT)12-18, but it could not use poly(rA)-oligo(dT)12-18, poly(rC)-oligo(dG)12-18, or oligo(dT)12-18. The enzyme requires Mg2+ for maximal activity, is sensitive to p-hydroxymercuribenzoate, and is not a zinc metalloenzyme. In addition, the cytomegalovirus-induced DNA polymerase activity can be enhanced by adding 0.06 to 0.12 M NaCl or 0.03 to 0.06 M (NH4)2SO4 to the reaction mixture."} {"id": "PMID:168405", "title": "Abortive infection of a rabbit cornea cell line by vesicular stomatitis virus: conversion to productive infection by superinfection with vaccinia virus.", "content": "An abortive infection of a rabbit cornea cell line (RC-60) by vesicular stomatitis virus (VSV), yielding less than 1 PFU/cell, was converted to a productive infection, yielding 1,900 PFU/cell, when cells were superinfected with vaccinia. Studies on the synthesis of VSV-directed RNA in RC-60 cells suggest that the abortive infection by VSV alone may be due in part to (i) a limited production of 40S virion RNA and (ii) a markedly reduced activity of virion-bound transcriptase activity in RC-60 cells compared to the activity in mouse L cells, a permissive host for VSV. No recognizable VSV structures, except a small amount of viral core structures, were produced by the abortive infection. In contrast, double infection of RC-60 cells with VSV and vaccinia in the presence of hydroxyurea resulted in the production of infective B particles of VSV. Although the function supplied by vaccinia responsible for the productive replication of VSV in double infected RC-60 cells has not been identified, metabolic inhibitor studies indicate that continuous vaccinia-dependent RNA synthesis is required for maximal production of infective VSV. The possibility is considered that vaccinia may supply a product or function required for VSV replication which is ordinarily supplied by the host but which is lacking in RC-60 cells.", "contents": "Abortive infection of a rabbit cornea cell line by vesicular stomatitis virus: conversion to productive infection by superinfection with vaccinia virus. An abortive infection of a rabbit cornea cell line (RC-60) by vesicular stomatitis virus (VSV), yielding less than 1 PFU/cell, was converted to a productive infection, yielding 1,900 PFU/cell, when cells were superinfected with vaccinia. Studies on the synthesis of VSV-directed RNA in RC-60 cells suggest that the abortive infection by VSV alone may be due in part to (i) a limited production of 40S virion RNA and (ii) a markedly reduced activity of virion-bound transcriptase activity in RC-60 cells compared to the activity in mouse L cells, a permissive host for VSV. No recognizable VSV structures, except a small amount of viral core structures, were produced by the abortive infection. In contrast, double infection of RC-60 cells with VSV and vaccinia in the presence of hydroxyurea resulted in the production of infective B particles of VSV. Although the function supplied by vaccinia responsible for the productive replication of VSV in double infected RC-60 cells has not been identified, metabolic inhibitor studies indicate that continuous vaccinia-dependent RNA synthesis is required for maximal production of infective VSV. The possibility is considered that vaccinia may supply a product or function required for VSV replication which is ordinarily supplied by the host but which is lacking in RC-60 cells."} {"id": "PMID:168406", "title": "Synthesis of functional bacteriophage T4-delayed early mRNA in the absence of protein synthesis.", "content": "When Escherichia coli B207 is grown either aerobically or under limited aerobic conditions, pretreated with chloramphenicol to block protein synthesis, and then infected with bacteriophage T4, the phage RNA which accumulates, termed \"immediately early\" (IE), contains the transcripts of a limited number of prereplicative genes. Among the transcripts which accumulate is the mRNA which serves as a template for deoxycytidylate hydroxymethylase (HMase) synthesis. Among the prereplicative gene transcripts which do not accumulate under these conditions are deoxycytidine triphosphatase (dCTPase), alpha-glucosyl transferase (alphg-gt), and deoxynucleotide kinase (kinase); these genes have been termed \"delayed early\" (DE). In contrast, when protein synthesis is inhibited by depleting aerobically grown E. coli B207 of K+, both IE and DE T4 RNA accumulate, but these transcripts do not contain functional HMase, dCTPase, alpha-gt, or kinase mRNA's. However, if E. coli is grown under conditions of limited aeration and then depleted of K+ prior to T4 infection, the T4 RNA which accumulates contains both IE and DE transcripts and functional HMase, dCTPase, and alpha-gt mRNA's. Functional kinase mRNA does not accumulate under these conditions. The results of these experiments indicate that the synthesis of functional DE RNA in the absence of simultaneous protein synthesis, depends on the physiological condition of the cells and the way in which protein synthesis is inhibited. In addition, data is presented which suggests that extensive transcription of DE genes in the absence of protein synthesis results in the inhibition of transcription of certain IE genes.", "contents": "Synthesis of functional bacteriophage T4-delayed early mRNA in the absence of protein synthesis. When Escherichia coli B207 is grown either aerobically or under limited aerobic conditions, pretreated with chloramphenicol to block protein synthesis, and then infected with bacteriophage T4, the phage RNA which accumulates, termed \"immediately early\" (IE), contains the transcripts of a limited number of prereplicative genes. Among the transcripts which accumulate is the mRNA which serves as a template for deoxycytidylate hydroxymethylase (HMase) synthesis. Among the prereplicative gene transcripts which do not accumulate under these conditions are deoxycytidine triphosphatase (dCTPase), alpha-glucosyl transferase (alphg-gt), and deoxynucleotide kinase (kinase); these genes have been termed \"delayed early\" (DE). In contrast, when protein synthesis is inhibited by depleting aerobically grown E. coli B207 of K+, both IE and DE T4 RNA accumulate, but these transcripts do not contain functional HMase, dCTPase, alpha-gt, or kinase mRNA's. However, if E. coli is grown under conditions of limited aeration and then depleted of K+ prior to T4 infection, the T4 RNA which accumulates contains both IE and DE transcripts and functional HMase, dCTPase, and alpha-gt mRNA's. Functional kinase mRNA does not accumulate under these conditions. The results of these experiments indicate that the synthesis of functional DE RNA in the absence of simultaneous protein synthesis, depends on the physiological condition of the cells and the way in which protein synthesis is inhibited. In addition, data is presented which suggests that extensive transcription of DE genes in the absence of protein synthesis results in the inhibition of transcription of certain IE genes."} {"id": "PMID:168407", "title": "Demyelination and cytopathic effects in cultures of mammalian dorsal root ganglia infected with encephalomyocarditis virus.", "content": "Replication of encephalomyocarditis virus and its cytopathic effects were studied in myelinated cultures of dorsal root ganglia obtained from newborn mice. Six hours after infection virus progeny was detected in the culture. At 24 h the virus titer reached 2 times 10(6) PFU per culture and remained at this level until 48 h. The first cytopathic alterations began at 24 h and consisted of rounding of Schwann and satellites cells and their detachment from neurons. Later, bead-like swellings of the myelin appeared along the axons followed by splitting and degeneration of lamellae. The cytopathic effect in the neurons started 29 h after infection, reaching complete neuronolysis at 48 h. Virus particles, scattered or arranged in crystal-like aggregates, were first seen in the cytoplasm of glial cells and then in neurons and axons.", "contents": "Demyelination and cytopathic effects in cultures of mammalian dorsal root ganglia infected with encephalomyocarditis virus. Replication of encephalomyocarditis virus and its cytopathic effects were studied in myelinated cultures of dorsal root ganglia obtained from newborn mice. Six hours after infection virus progeny was detected in the culture. At 24 h the virus titer reached 2 times 10(6) PFU per culture and remained at this level until 48 h. The first cytopathic alterations began at 24 h and consisted of rounding of Schwann and satellites cells and their detachment from neurons. Later, bead-like swellings of the myelin appeared along the axons followed by splitting and degeneration of lamellae. The cytopathic effect in the neurons started 29 h after infection, reaching complete neuronolysis at 48 h. Virus particles, scattered or arranged in crystal-like aggregates, were first seen in the cytoplasm of glial cells and then in neurons and axons."} {"id": "PMID:168408", "title": "Structure, subunit composition, and molecular weight of RD-114 RNA.", "content": "The properties and subunit composition of the RNA extracted from RD-114 virions have been studied. The RNA extracted from the virion has a sedimentation coefficient of 52S in a nondenaturing aqueous electrolyte. The estimated molecular weight by sedimentation in nondenaturing and weakly denaturing media is in the range 5.7 X 10(6) to 7.0 X 10(6). By electron microscopy, under moderately denaturing conditions, the 52S molecule is seen to be an extended single strand with a contour length of about 4.0 mum corresponding to a molecular weight of 5.74 X 10(6). It contains two characteristic secondary structure features: (i) a central Y- or T-shaped structure (the rabbit ears) with a molecular weight of 0.3 X 10(6), (ii) two symmetreically disposed loops on each side of and at equal distance from the center. The 52S molecule consists of two half-size molecules, with molecular weight 2.8 X 10(6), joined together within the central rabbit ears feature. Melting of the rabbit ears with concomitant dissociation of the 52S molecule into subunits, has been caused by either one of two strongly denaturing treatments: incubation in a mixture of CH3HgOH and glyoxal at room temperature, or thermal dissociation in a urea-formamide solvent. When half-size molecules are quenched from denaturing temperatures, a new off-center secondary structure feature termed the branch-like structure is seen. The dissociation behavior of the 52S complex and the molecular weight of the subunits have been confirmed by gel electrophoresis studies. The loop structures melt at fairly low temperatures; the dissociation of the 52S molecule into its two subunits occurs at a higher temperature corresponding to a base composition of about 63% guanosine plus cytosine. Polyadenylic acid mapping by electron microscopy shows that the 52S molecule contains two polyadenylic acid segments, one at each end. It thus appears that 52S RD-114 RNA consists of two 2.8 X 10(6) dalton subunits, each with a characteristic secondary structure loop, and joined at the 5' ends to form the rabbit ears secondary structure feature. The observations are consistent with but do not require the conclusion that the two 2.8 X 10(6) dalton subunits of 52S RD-114 RNA are identical.", "contents": "Structure, subunit composition, and molecular weight of RD-114 RNA. The properties and subunit composition of the RNA extracted from RD-114 virions have been studied. The RNA extracted from the virion has a sedimentation coefficient of 52S in a nondenaturing aqueous electrolyte. The estimated molecular weight by sedimentation in nondenaturing and weakly denaturing media is in the range 5.7 X 10(6) to 7.0 X 10(6). By electron microscopy, under moderately denaturing conditions, the 52S molecule is seen to be an extended single strand with a contour length of about 4.0 mum corresponding to a molecular weight of 5.74 X 10(6). It contains two characteristic secondary structure features: (i) a central Y- or T-shaped structure (the rabbit ears) with a molecular weight of 0.3 X 10(6), (ii) two symmetreically disposed loops on each side of and at equal distance from the center. The 52S molecule consists of two half-size molecules, with molecular weight 2.8 X 10(6), joined together within the central rabbit ears feature. Melting of the rabbit ears with concomitant dissociation of the 52S molecule into subunits, has been caused by either one of two strongly denaturing treatments: incubation in a mixture of CH3HgOH and glyoxal at room temperature, or thermal dissociation in a urea-formamide solvent. When half-size molecules are quenched from denaturing temperatures, a new off-center secondary structure feature termed the branch-like structure is seen. The dissociation behavior of the 52S complex and the molecular weight of the subunits have been confirmed by gel electrophoresis studies. The loop structures melt at fairly low temperatures; the dissociation of the 52S molecule into its two subunits occurs at a higher temperature corresponding to a base composition of about 63% guanosine plus cytosine. Polyadenylic acid mapping by electron microscopy shows that the 52S molecule contains two polyadenylic acid segments, one at each end. It thus appears that 52S RD-114 RNA consists of two 2.8 X 10(6) dalton subunits, each with a characteristic secondary structure loop, and joined at the 5' ends to form the rabbit ears secondary structure feature. The observations are consistent with but do not require the conclusion that the two 2.8 X 10(6) dalton subunits of 52S RD-114 RNA are identical."} {"id": "PMID:168409", "title": "Further evidence for the existence of a viral envelope protein defect in the Bryan high-titer strain of Rous sarcoma virus.", "content": "Electron microscopy observations of purified Bryan high-titer Rous sarcoma virus (BH RSV) using the freeze-drying technique showed that progeny made in the absence of a helper virus lacked visible surface projections or spikes. Phenotypic mixing experiments employing BH RSV and a thermolabile mutant of vesicular stomatitis virus, tl 17, yielded no evidence of pseudotype formation. Since tl 17 is known to be defective for an envelope glycoprotein, the lack of successful phenotypic mixing with BH RSV is consistent with the observed absence of viral spikes.", "contents": "Further evidence for the existence of a viral envelope protein defect in the Bryan high-titer strain of Rous sarcoma virus. Electron microscopy observations of purified Bryan high-titer Rous sarcoma virus (BH RSV) using the freeze-drying technique showed that progeny made in the absence of a helper virus lacked visible surface projections or spikes. Phenotypic mixing experiments employing BH RSV and a thermolabile mutant of vesicular stomatitis virus, tl 17, yielded no evidence of pseudotype formation. Since tl 17 is known to be defective for an envelope glycoprotein, the lack of successful phenotypic mixing with BH RSV is consistent with the observed absence of viral spikes."} {"id": "PMID:168410", "title": "Association of ribosomes with intracellular vesicular stomatitis virus particles.", "content": "Ribosomes are observed intimately associated with nucleocapsids of vesicular, stomatitis virus, especially those that line structures that are either cytoplasmic vesicles or invaginations of the plasma membrane.", "contents": "Association of ribosomes with intracellular vesicular stomatitis virus particles. Ribosomes are observed intimately associated with nucleocapsids of vesicular, stomatitis virus, especially those that line structures that are either cytoplasmic vesicles or invaginations of the plasma membrane."} {"id": "PMID:168411", "title": "Poxvirus infection in the white-backed magpie (Gymnorhina hypoleuca) and pox-like conditions in other birds in Australia.", "content": "Lesions, grossly and histologically typical of pox infection, occurred in a white-backed magpie from Melbourne, Australia. Electron microscopic examination revealed typical poxvirus particles in lesion material. The disease was experimentally transmitted to other magpies, but chickens, turkeys, pigeons, and canaries were refractory to experimental infection with magpie poxvirus. The epidemiology of magpie pox and the probable occurrence of pox-like disease in other native Australian birds are discussed.", "contents": "Poxvirus infection in the white-backed magpie (Gymnorhina hypoleuca) and pox-like conditions in other birds in Australia. Lesions, grossly and histologically typical of pox infection, occurred in a white-backed magpie from Melbourne, Australia. Electron microscopic examination revealed typical poxvirus particles in lesion material. The disease was experimentally transmitted to other magpies, but chickens, turkeys, pigeons, and canaries were refractory to experimental infection with magpie poxvirus. The epidemiology of magpie pox and the probable occurrence of pox-like disease in other native Australian birds are discussed."} {"id": "PMID:168415", "title": "Epithelioid granulomas in Hodgkin disease. A favorable prognostic sign?", "content": "Histologic sections of spleen and liver prepared from tissue obtained during exploratory laparotomy and splenectomy in 91 untreated patients with Hodgkin disease were reviewed to assess the incidence and possible implications of noncaseating, epitheliod, sarcoid-like granulomas. The 17 patients with granulomas and the 74 patients without granulomas did not differ appreciably with respect to pretreatment indexes. All patients were observed for at least 15 months following laparotomy or until the time of death (range, 15 to 67 months; median, 25 months). The 17 patients with granulomas tended to have fewer relapses, longer survival, and lower incidence of subsequent herpes zoster infection compared to the 74 without granulomas. The presence of epithelioid granulomas in association with Hodgkin disease may reflect a host response to the tumor with favorable prognostic implications.", "contents": "Epithelioid granulomas in Hodgkin disease. A favorable prognostic sign? Histologic sections of spleen and liver prepared from tissue obtained during exploratory laparotomy and splenectomy in 91 untreated patients with Hodgkin disease were reviewed to assess the incidence and possible implications of noncaseating, epitheliod, sarcoid-like granulomas. The 17 patients with granulomas and the 74 patients without granulomas did not differ appreciably with respect to pretreatment indexes. All patients were observed for at least 15 months following laparotomy or until the time of death (range, 15 to 67 months; median, 25 months). The 17 patients with granulomas tended to have fewer relapses, longer survival, and lower incidence of subsequent herpes zoster infection compared to the 74 without granulomas. The presence of epithelioid granulomas in association with Hodgkin disease may reflect a host response to the tumor with favorable prognostic implications."} {"id": "PMID:168417", "title": "Hepatitis types B and non-B. Epidemiologic background.", "content": "Two episodes of acute viral hepatitis occurred in each of 34 patients. One episode in each patient was serologically diagnosable as type B hepatitis on the basis of tests for hepatitis B surface antigen or antibody. The other episode was classified as \"non-B\" on the basis of seronegativity, reinforced by seropositivity in an alternate bout. An epidemiologic background appropriate to \"serum\" hepatitis, either transfusion (one bout) or illicit self-injection (46 bouts), was associated just as frequently with serologically non-B episodes as with identified type B disease. The diagnosis of type B hepatitis, therefore, should be made only on the basis of serologic tests specific for hepatitis B virus infection. Other cases of sporadic diseases in adults must be labeled \"viral hepatitis, type unspecifiable.\"", "contents": "Hepatitis types B and non-B. Epidemiologic background. Two episodes of acute viral hepatitis occurred in each of 34 patients. One episode in each patient was serologically diagnosable as type B hepatitis on the basis of tests for hepatitis B surface antigen or antibody. The other episode was classified as \"non-B\" on the basis of seronegativity, reinforced by seropositivity in an alternate bout. An epidemiologic background appropriate to \"serum\" hepatitis, either transfusion (one bout) or illicit self-injection (46 bouts), was associated just as frequently with serologically non-B episodes as with identified type B disease. The diagnosis of type B hepatitis, therefore, should be made only on the basis of serologic tests specific for hepatitis B virus infection. Other cases of sporadic diseases in adults must be labeled \"viral hepatitis, type unspecifiable.\""} {"id": "PMID:168422", "title": "Requirement of newly synthesized protein for the priming activity of interferon.", "content": "Pretreatment of mouse L cells with interferon (IF) enhanced IF production in response to polyinosinic-polycytidylic acid (poly I-poly C). Post-treatment of cells with IF caused no significant enhancement of IF production. The enhancing effect of IF pretreatment (priming) reached a maximum after incubation with IF (10 or 100 units/ml) for 4-6 hr at 37 C, but this effect was absent when the incubation was done at 4 C. Cells which were incubated for additional several hours at 37 C after IF pretreatment at 4 C did not develop the primed state nor the antiviral state. The presence of protein synthesis inhibitors during the IF pretreatment depressed, though not completely, the development of the primed state. The residual priming effect was lost when the cells were incubated with the inhibitors at 37 C for 2 hr before they were exposed to poly I-poly C. There was no significant difference in the binding rate of poly I-poly C to cells between IF-treated and untreated cells. The degradation rate of cell-bound poly I-poly C and its sensitivity to exogenous pancreatic ribonuclease in the pretreated cells were also similar to those in the untreated cells.", "contents": "Requirement of newly synthesized protein for the priming activity of interferon. Pretreatment of mouse L cells with interferon (IF) enhanced IF production in response to polyinosinic-polycytidylic acid (poly I-poly C). Post-treatment of cells with IF caused no significant enhancement of IF production. The enhancing effect of IF pretreatment (priming) reached a maximum after incubation with IF (10 or 100 units/ml) for 4-6 hr at 37 C, but this effect was absent when the incubation was done at 4 C. Cells which were incubated for additional several hours at 37 C after IF pretreatment at 4 C did not develop the primed state nor the antiviral state. The presence of protein synthesis inhibitors during the IF pretreatment depressed, though not completely, the development of the primed state. The residual priming effect was lost when the cells were incubated with the inhibitors at 37 C for 2 hr before they were exposed to poly I-poly C. There was no significant difference in the binding rate of poly I-poly C to cells between IF-treated and untreated cells. The degradation rate of cell-bound poly I-poly C and its sensitivity to exogenous pancreatic ribonuclease in the pretreated cells were also similar to those in the untreated cells."} {"id": "PMID:168423", "title": "Participation of mono- and polysynaptic transmission during tonic activation of the stretch reflex arcs.", "content": "Through intracellular observations of the cat spinal motoneuron both mono- and polysynaptic reflex arcs were shown to participate in repetitive activation of stretch reflex. Experiments were performed on 25 cats anesthetized by intraperitoneal (i.p.) injection of 3 cc/kg of a mixture of 1% chloralose and 10% urethane. Driving of the motoneuronal discharges accomplished by electric stimulation (16-100 Hz) of the gastrocnemius lateralis and medialis nerves. Repeated electric stimulation of muscle nerves elicited monosynaptic \"vibratory\" EPSPs and a polysynaptic \"augmenting\" EPSP in the motoneuron. The firing of the motoneuron occurred when a temporal summation of the \"vibratory\" EPSPs was sufficiently obtained. The discharge frequency of motoneuron, MNf, was expressed as a product of electrostimulus frequency, Sf, and reciprocal of an integer, n, i.e. MNf=(1/n)Sf. An increase in the stimulus intensity resulted in a dimimution of the vibratory EPSP and a remarkable increase of n. This was assumed to be due to an inhibitory process produced by the Group II fibers. The minimum value of integer n was always a determinant factor for the maximum value of MNf which was referred to as the \"preferred\" frequency of the motoneuron. Long-lasting electric stimulation of muscle nerves was followed by a more remarkable recruitment of the augmenting EPSP which made the motoneuron attain its critical threshold of firing. Motoneuronal spikes elicited by such a large augmenting EPSP were not locked to the Ia impulses. Unlocked spikes were observed only in a later stage of electric stimulation of Ia fibers.", "contents": "Participation of mono- and polysynaptic transmission during tonic activation of the stretch reflex arcs. Through intracellular observations of the cat spinal motoneuron both mono- and polysynaptic reflex arcs were shown to participate in repetitive activation of stretch reflex. Experiments were performed on 25 cats anesthetized by intraperitoneal (i.p.) injection of 3 cc/kg of a mixture of 1% chloralose and 10% urethane. Driving of the motoneuronal discharges accomplished by electric stimulation (16-100 Hz) of the gastrocnemius lateralis and medialis nerves. Repeated electric stimulation of muscle nerves elicited monosynaptic \"vibratory\" EPSPs and a polysynaptic \"augmenting\" EPSP in the motoneuron. The firing of the motoneuron occurred when a temporal summation of the \"vibratory\" EPSPs was sufficiently obtained. The discharge frequency of motoneuron, MNf, was expressed as a product of electrostimulus frequency, Sf, and reciprocal of an integer, n, i.e. MNf=(1/n)Sf. An increase in the stimulus intensity resulted in a dimimution of the vibratory EPSP and a remarkable increase of n. This was assumed to be due to an inhibitory process produced by the Group II fibers. The minimum value of integer n was always a determinant factor for the maximum value of MNf which was referred to as the \"preferred\" frequency of the motoneuron. Long-lasting electric stimulation of muscle nerves was followed by a more remarkable recruitment of the augmenting EPSP which made the motoneuron attain its critical threshold of firing. Motoneuronal spikes elicited by such a large augmenting EPSP were not locked to the Ia impulses. Unlocked spikes were observed only in a later stage of electric stimulation of Ia fibers."} {"id": "PMID:168424", "title": "Antiphosphodiesterase activity and nonspecific smooth muscle relaxation tested on intestinal smooth muscles.", "content": "Mitochondrial, microsomal and soluble fractions separated from the guinea pig taenia and from the dog longitudinal smooth muscle were used as phosphodiesterase preparation. Each preparation had low and high Km values, indicating the existence of at least two kinds of phosphodiesterase. Papaverine and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride), hydralazine, caffeine Na benzoate and aminophylline were used at test drugs. Aspaminol had little inhibitory effect on phosphodiesterase. Ki value of papaverine almost equalled the concentration (M) which was necessary to produce 50% relaxation. Relaxation of the guinea pig taenia by papaverine was preceded by an increase of intracellular cyclic AMP,. Therefore, the action of papaverine is likely to be mediated by an increase in cyclic AMP, which is caused by inhibition of the phosphodiesterase-catalyzed breakdown of cyclic AMP. There was little correlation between relaxing activities of the drugs used and their antiphosphodiesterase activities. Relaxation of the smooth muscle induced by the smooth muscle relaxants excepting papaverine is not due to inhibition of phosphodiesterase.", "contents": "Antiphosphodiesterase activity and nonspecific smooth muscle relaxation tested on intestinal smooth muscles. Mitochondrial, microsomal and soluble fractions separated from the guinea pig taenia and from the dog longitudinal smooth muscle were used as phosphodiesterase preparation. Each preparation had low and high Km values, indicating the existence of at least two kinds of phosphodiesterase. Papaverine and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride), hydralazine, caffeine Na benzoate and aminophylline were used at test drugs. Aspaminol had little inhibitory effect on phosphodiesterase. Ki value of papaverine almost equalled the concentration (M) which was necessary to produce 50% relaxation. Relaxation of the guinea pig taenia by papaverine was preceded by an increase of intracellular cyclic AMP,. Therefore, the action of papaverine is likely to be mediated by an increase in cyclic AMP, which is caused by inhibition of the phosphodiesterase-catalyzed breakdown of cyclic AMP. There was little correlation between relaxing activities of the drugs used and their antiphosphodiesterase activities. Relaxation of the smooth muscle induced by the smooth muscle relaxants excepting papaverine is not due to inhibition of phosphodiesterase."} {"id": "PMID:168428", "title": "Murine virus susceptibility of cell cultures of mouse, rat, hamster, monkey, and human origin.", "content": "Studies were initiated to determine the practicality of using various tissue cultures for the propagation of murine viruses isolated from laboratory animals. The cytopathogenic effects of 10 murine viruses known to cause disease in laboratory rodents were compared in monolayer cultures of L929, BHK-21, WI-38, BSC-1, and Vero cells. The susceptibility of primary hamster embryo, hamster kidney, mouse embryo, mouse kidney, and rat embryo cell cultures was also tested. Seven of the viruses produced effects in at least 1 of the cell substrates. The remaining 3 viruses, namely H-1, K, and mouse hepatitis, produced no effects in the cell cultures tested.", "contents": "Murine virus susceptibility of cell cultures of mouse, rat, hamster, monkey, and human origin. Studies were initiated to determine the practicality of using various tissue cultures for the propagation of murine viruses isolated from laboratory animals. The cytopathogenic effects of 10 murine viruses known to cause disease in laboratory rodents were compared in monolayer cultures of L929, BHK-21, WI-38, BSC-1, and Vero cells. The susceptibility of primary hamster embryo, hamster kidney, mouse embryo, mouse kidney, and rat embryo cell cultures was also tested. Seven of the viruses produced effects in at least 1 of the cell substrates. The remaining 3 viruses, namely H-1, K, and mouse hepatitis, produced no effects in the cell cultures tested."} {"id": "PMID:168429", "title": "Application of agar-gel precipitin test for the detection of Sendai virus antibody in rat sera.", "content": "A simplified agar-gel precipitin test was performed for the detection of Sendai virus antibody in rat sera. A close correlation was observed between detection of antibodies by complement-fixation test and agar-gel precipitin test. No correlation was found between results obtained by hemagglutination-inhibition test and agar-gel precipitin test in sera with HI titer of less than 1:8.", "contents": "Application of agar-gel precipitin test for the detection of Sendai virus antibody in rat sera. A simplified agar-gel precipitin test was performed for the detection of Sendai virus antibody in rat sera. A close correlation was observed between detection of antibodies by complement-fixation test and agar-gel precipitin test. No correlation was found between results obtained by hemagglutination-inhibition test and agar-gel precipitin test in sera with HI titer of less than 1:8."} {"id": "PMID:168435", "title": "Interaction of the 5'-ends of 28S RNA in dimerization of hamster ribosomes.", "content": "Free ribosomes extracted from hamster cells and 28S RNA purified from these ribosomes are known to form dimers. We find that spleen phosphodiesterase inhibits ribosomal dimer formation, but only when a free 5'-hydroxyl end group, produced by the action of alkaline phosphatase, is present. Hence, formation of dimer ribosomes probably involves interaction at or near the phosphorylated 5'-ends of 28S RNA. Dimer RNA molecules show a modal length, when measured on electrom micrographs, of 2.1 mum, which is about double the length of 28S RNA. Electron micrographs of 115S dimer ribosomes often show profiles consistent with our interpretation that in dimers the 28S RNA chains are loosely linked by their 5'-ends.", "contents": "Interaction of the 5'-ends of 28S RNA in dimerization of hamster ribosomes. Free ribosomes extracted from hamster cells and 28S RNA purified from these ribosomes are known to form dimers. We find that spleen phosphodiesterase inhibits ribosomal dimer formation, but only when a free 5'-hydroxyl end group, produced by the action of alkaline phosphatase, is present. Hence, formation of dimer ribosomes probably involves interaction at or near the phosphorylated 5'-ends of 28S RNA. Dimer RNA molecules show a modal length, when measured on electrom micrographs, of 2.1 mum, which is about double the length of 28S RNA. Electron micrographs of 115S dimer ribosomes often show profiles consistent with our interpretation that in dimers the 28S RNA chains are loosely linked by their 5'-ends."} {"id": "PMID:168436", "title": "Duodenoscopy and endoscopic retrograde choledochopancreatography: present position in relation to periampullary and pancreatic cancer.", "content": "Duodenoscopy and endoscopic retrograde choledochopancreatography represent a major advance in the diagnosis of periampullary and pancreatic lesions. Instruments, techniques and complications are reviewed. A combination of endoscopy and ERCP will yield diagnosis in a high proportion of patients suspected of pancreatic or ampullary carcinomata. Information is obtained which is not only of diagnostic value but is important in the surgical treatment of such patients.", "contents": "Duodenoscopy and endoscopic retrograde choledochopancreatography: present position in relation to periampullary and pancreatic cancer. Duodenoscopy and endoscopic retrograde choledochopancreatography represent a major advance in the diagnosis of periampullary and pancreatic lesions. Instruments, techniques and complications are reviewed. A combination of endoscopy and ERCP will yield diagnosis in a high proportion of patients suspected of pancreatic or ampullary carcinomata. Information is obtained which is not only of diagnostic value but is important in the surgical treatment of such patients."} {"id": "PMID:168437", "title": "Radiologic diagnosis of pancreatic cancer.", "content": "Modern radiology makes possible an accurate diagnosis of pancreatic cancer in about 95 percent of cases. Conventional upper gastrointestinal study, isotopic scanning, hypotonic duodenography, and ultrasonography are suitable as screening procedures. Special methods of high accuracy - pancreatic arteriography, endoscopic pancreatography, and transhepatic cholangiography are used as needed for definitive diagnosis.", "contents": "Radiologic diagnosis of pancreatic cancer. Modern radiology makes possible an accurate diagnosis of pancreatic cancer in about 95 percent of cases. Conventional upper gastrointestinal study, isotopic scanning, hypotonic duodenography, and ultrasonography are suitable as screening procedures. Special methods of high accuracy - pancreatic arteriography, endoscopic pancreatography, and transhepatic cholangiography are used as needed for definitive diagnosis."} {"id": "PMID:168438", "title": "Carcinoma of the exocrine pancreas: pathologic aspects.", "content": "This discussion is based upon 205 autopsied cases of carcinoma of the pancreas. Sixty-six percent were male, eighty percent white, mean age 61.5 years. Fifty-three percent of tumors occurred in the head of the pancreas. Most lesions were moderately well-differentiated adenocarcinomas. Pathologic aspects of carcinoma of the pancreas are discussed.", "contents": "Carcinoma of the exocrine pancreas: pathologic aspects. This discussion is based upon 205 autopsied cases of carcinoma of the pancreas. Sixty-six percent were male, eighty percent white, mean age 61.5 years. Fifty-three percent of tumors occurred in the head of the pancreas. Most lesions were moderately well-differentiated adenocarcinomas. Pathologic aspects of carcinoma of the pancreas are discussed."} {"id": "PMID:168439", "title": "The relationship of histology to the spread of cancer.", "content": "This paper investigates the question of whether different types of histology at the same site can affect the spread of metastases - that is, producing a greater or fewer number of metastases depending on the histological diagnosis. Autopsy records were the source of the data analyzed in this paper. The metastases were subdivided into four categories - central nervous metastases, endocrine metastases, metastases at various lymphatic areas, and a miscellaneous group of metastases called the \"remainder\" group. It was found that adenocarcinoma and oat-cell carcinoma of the lungs are more aggressive in their metastatic spread than squamous cell carcinoma at the same site. Adenocarcinoma of the cervix uteri had more widespread metastases than squamous cell carcinoma at the same site. No difference at all was detectable in the number of metastases, in men or in women, between transitional cell carcinoma and adenocarcinoma of the bladder and kidney. Cystadenocarcinoma of the ovaries appeared to be less widespread than adenocarcinoma (not otherwise specified) of the same site.", "contents": "The relationship of histology to the spread of cancer. This paper investigates the question of whether different types of histology at the same site can affect the spread of metastases - that is, producing a greater or fewer number of metastases depending on the histological diagnosis. Autopsy records were the source of the data analyzed in this paper. The metastases were subdivided into four categories - central nervous metastases, endocrine metastases, metastases at various lymphatic areas, and a miscellaneous group of metastases called the \"remainder\" group. It was found that adenocarcinoma and oat-cell carcinoma of the lungs are more aggressive in their metastatic spread than squamous cell carcinoma at the same site. Adenocarcinoma of the cervix uteri had more widespread metastases than squamous cell carcinoma at the same site. No difference at all was detectable in the number of metastases, in men or in women, between transitional cell carcinoma and adenocarcinoma of the bladder and kidney. Cystadenocarcinoma of the ovaries appeared to be less widespread than adenocarcinoma (not otherwise specified) of the same site."} {"id": "PMID:168440", "title": "Malignant melanoma and carcinoma of the breast.", "content": "Five patients with breast cancer and malignant melanoma are reported. Two patients had a third primary malignancy. In 4 out of 5 patients the breast tumor was the initial tumor discovered, and in 4 out of 5 the second tumor evolved metachronously. No specific carcinogenic factor could be established. The low malignancy potential of the melanoma by pathologic criteria may explain the lack of previous reports of this association.", "contents": "Malignant melanoma and carcinoma of the breast. Five patients with breast cancer and malignant melanoma are reported. Two patients had a third primary malignancy. In 4 out of 5 patients the breast tumor was the initial tumor discovered, and in 4 out of 5 the second tumor evolved metachronously. No specific carcinogenic factor could be established. The low malignancy potential of the melanoma by pathologic criteria may explain the lack of previous reports of this association."} {"id": "PMID:168443", "title": "Oat cell carcinoma as a malignant apudoma.", "content": "The neural crest origin of cells secreting amine and polypeptide hormones (APUD cells) is a unifying concept. The relationship of the classical endocrine system to that of tumor hormone secretion can be explained by the diffuse migration and later neoplasia of these unique cells. This paper describes the APUD cell origins of oat cell carcinoma.", "contents": "Oat cell carcinoma as a malignant apudoma. The neural crest origin of cells secreting amine and polypeptide hormones (APUD cells) is a unifying concept. The relationship of the classical endocrine system to that of tumor hormone secretion can be explained by the diffuse migration and later neoplasia of these unique cells. This paper describes the APUD cell origins of oat cell carcinoma."} {"id": "PMID:168445", "title": "Cyclic AMP and adenylate cyclase in the inner ear.", "content": "The activity of adenylate cyclase and the steady state levels of cyclic AMP (cAMP) were determined in stria vascularis (SV) and organ of Corti (OC) of the guinea pig cochlea. The activities are 12 and 19 pmoles/mg dry weight/minute for OC and SV, respectively. The activity was increased two to four-fold by NaF. The base level of cAMP is 4.2 and 4.4 nmoles/g dry weight in OC and SV, respectively. In contrast to brain, neither ischemia nor barbiturates produced major changes of the steady state levels of cAMP. No in vitro effect of cAMP upon the state of activation of glycogen phosphorylase was noticeable in either tissue. cAMP did not exert a significant in vitro inhibition of strial Na+K+-ATPase. Perilymphatic perfusion of cAMP (10-3 M) and of theophylline (5 times 10-3 M) did not produce changes in the endolymphatic potential (EP), but dibutyryl cAMP (10-3 M) led to a significant increase of EP. The alpha adrenergic blocking agent, phentolamine, produced very complex changes of the cochlear potentials. A possible role of catecholamines and cAMP in the secretory phenomena of the SV and in the transduction and/or transmission processes of the auditory sense organ are discussed.", "contents": "Cyclic AMP and adenylate cyclase in the inner ear. The activity of adenylate cyclase and the steady state levels of cyclic AMP (cAMP) were determined in stria vascularis (SV) and organ of Corti (OC) of the guinea pig cochlea. The activities are 12 and 19 pmoles/mg dry weight/minute for OC and SV, respectively. The activity was increased two to four-fold by NaF. The base level of cAMP is 4.2 and 4.4 nmoles/g dry weight in OC and SV, respectively. In contrast to brain, neither ischemia nor barbiturates produced major changes of the steady state levels of cAMP. No in vitro effect of cAMP upon the state of activation of glycogen phosphorylase was noticeable in either tissue. cAMP did not exert a significant in vitro inhibition of strial Na+K+-ATPase. Perilymphatic perfusion of cAMP (10-3 M) and of theophylline (5 times 10-3 M) did not produce changes in the endolymphatic potential (EP), but dibutyryl cAMP (10-3 M) led to a significant increase of EP. The alpha adrenergic blocking agent, phentolamine, produced very complex changes of the cochlear potentials. A possible role of catecholamines and cAMP in the secretory phenomena of the SV and in the transduction and/or transmission processes of the auditory sense organ are discussed."} {"id": "PMID:168444", "title": "Phosphodiesterase and adenyl-cyclase activities in the cerebral cotex of the aging rat.", "content": "In an effort to determine the factors responsible for the four-fold decrease in cyclic-AMP content of the rat cerebral cortex, observed to occur between the ages of 3 and 6 months, studies were performed on adenyl-cyclase and phosphodiesterase, the cyclic-AMP synthesizing and hydrolyzing enzymes. The activities and kinetic characteristics were determined for both enzymes as obtained from the cerebral cortex of rats ranging in age from one to 24 months. No age dependence was observed either in adenyl-cyclase activity, assayed with or without fluoride ion, or in phosphodiesterase activity. It was concluded that age related changes in factors other than the direc levels of these enzymes underlie the age related decline in cortical cyclic-AMP levels.", "contents": "Phosphodiesterase and adenyl-cyclase activities in the cerebral cotex of the aging rat. In an effort to determine the factors responsible for the four-fold decrease in cyclic-AMP content of the rat cerebral cortex, observed to occur between the ages of 3 and 6 months, studies were performed on adenyl-cyclase and phosphodiesterase, the cyclic-AMP synthesizing and hydrolyzing enzymes. The activities and kinetic characteristics were determined for both enzymes as obtained from the cerebral cortex of rats ranging in age from one to 24 months. No age dependence was observed either in adenyl-cyclase activity, assayed with or without fluoride ion, or in phosphodiesterase activity. It was concluded that age related changes in factors other than the direc levels of these enzymes underlie the age related decline in cortical cyclic-AMP levels."} {"id": "PMID:168454", "title": "Insulin and proinsulin release during calcium infusion in a patient with islet-cell tumor.", "content": "The infusion of calcium results in the release of gastrin, calcitonin, and serotonin from certain nonbeta islet cell tumors of the pancreas, medullary carcinomas of the thyroid, and carcinoid tumors, respectively. In this study, intravenous infusion of either calcium chloride or calcium aluconate in a patient with an islet-cell carcinoma resulted in a simultaneous rise in plasma immunoreactive insulin and proinsulin, and concurrent hypoglycemia. After resection of the tumor, calcium infusion caused no change in these parameters. Similarly, calcium infusion caused no change in plasma insulin or glucose in normal volunteers. The response of this tumor suggests that calcium infusion may be a useful provocative test to detect insulin-secreting neoplasia. A derangement of the stimulus-secretion coupling mechanism for insulin in the tumor cells may be responsible for their abnormal sensitivity to calcium ion.", "contents": "Insulin and proinsulin release during calcium infusion in a patient with islet-cell tumor. The infusion of calcium results in the release of gastrin, calcitonin, and serotonin from certain nonbeta islet cell tumors of the pancreas, medullary carcinomas of the thyroid, and carcinoid tumors, respectively. In this study, intravenous infusion of either calcium chloride or calcium aluconate in a patient with an islet-cell carcinoma resulted in a simultaneous rise in plasma immunoreactive insulin and proinsulin, and concurrent hypoglycemia. After resection of the tumor, calcium infusion caused no change in these parameters. Similarly, calcium infusion caused no change in plasma insulin or glucose in normal volunteers. The response of this tumor suggests that calcium infusion may be a useful provocative test to detect insulin-secreting neoplasia. A derangement of the stimulus-secretion coupling mechanism for insulin in the tumor cells may be responsible for their abnormal sensitivity to calcium ion."} {"id": "PMID:168455", "title": "Lp(a) lipoprotein: relationship to sinking pre-beta lipoprotein hyperlipoproteinemia, and apolipoprotein B.", "content": "To assess the relationship between the Lp(a) and the \"sinking pre-beta\" (d smaller than 1.006) lipoprotein, the concentration of Lp(a) was quantified by radial immunodiffusion and the presence or absence of sinking pre-beta was assessed by agarose electrophoresis in overnight fasting plasma samples from 485 adults, comprised of 320 with normal lipid levels, 48 with type IIa, 40 with type IIb, and 77 with type IV lipoprotein phenotypes. The median Lp(a) level was 7.6 mg/100 ml, 89% (433 of 485) having detectable Lp(a) levels. Twenty-two per cent (107 of 485) had detectable pre-beta lipoprotein in the d greater than 1.006 plasma fraction (sinking pre-beta). Of the sinking pre-beta positive plasma samples, 96% (102 and 107) exceeded the median Lp(a) level, and sinking pre-beta was detected in all 44 samples with an Lp(a) concentration exceeding 40 mg/100 ml. The relationship of Lp(a) and sinking pre-beta to lipoprotein phenotype was assessed. Compared to the normolipidemic group, the type IIa group had higher Lp(a) percentile values (p smaller than 0.02), whereas the IIb and type IV groups had significantly lower Lp(a) values than the normolipidemic group. Ninety-two per cent (296 of 320) of the normolipidemic subjects had detectable levels of Lp(a) and 22% (70 of 320) had detectable sinking pre-beta lipoprotein. Ninety-four per cent (45 of 48) of the type IIa plasmas had detectable Lp(a) levels and 27% (13 of 48) had sinking pre-beta lipoproteins. Contrasted with the IIa group, only 80% (32 of 40) of the IIb plasmas had detectable Lp(a) levels and 18% (7 of 40) had sinking pre-beta lipoprotein. In the type IV plasmas 78% (60 of 77) had detectable Lp(a) and 22% (17 of 77) had sinking pre-beta lipoprotein. Lp(a) or log Lp(a) levels were not correlated with apolipoprotein B levels (n = 485, r = 0.002 or 0.037, respectively). Furthermore, Lp(a) levels remained essentially constant in three subjects whose aprptein B levels were altered in response to pharmacological and/or dietary manipulation. A fourth subject had a 50% increase in Lp(a) but this change did not correlate with apoprotein B changes. Thus, these findings suggest that Lp(a) is metabolically independnet of low density lipoprotein even though it shares the same structural protein, apoprotein B.", "contents": "Lp(a) lipoprotein: relationship to sinking pre-beta lipoprotein hyperlipoproteinemia, and apolipoprotein B. To assess the relationship between the Lp(a) and the \"sinking pre-beta\" (d smaller than 1.006) lipoprotein, the concentration of Lp(a) was quantified by radial immunodiffusion and the presence or absence of sinking pre-beta was assessed by agarose electrophoresis in overnight fasting plasma samples from 485 adults, comprised of 320 with normal lipid levels, 48 with type IIa, 40 with type IIb, and 77 with type IV lipoprotein phenotypes. The median Lp(a) level was 7.6 mg/100 ml, 89% (433 of 485) having detectable Lp(a) levels. Twenty-two per cent (107 of 485) had detectable pre-beta lipoprotein in the d greater than 1.006 plasma fraction (sinking pre-beta). Of the sinking pre-beta positive plasma samples, 96% (102 and 107) exceeded the median Lp(a) level, and sinking pre-beta was detected in all 44 samples with an Lp(a) concentration exceeding 40 mg/100 ml. The relationship of Lp(a) and sinking pre-beta to lipoprotein phenotype was assessed. Compared to the normolipidemic group, the type IIa group had higher Lp(a) percentile values (p smaller than 0.02), whereas the IIb and type IV groups had significantly lower Lp(a) values than the normolipidemic group. Ninety-two per cent (296 of 320) of the normolipidemic subjects had detectable levels of Lp(a) and 22% (70 of 320) had detectable sinking pre-beta lipoprotein. Ninety-four per cent (45 of 48) of the type IIa plasmas had detectable Lp(a) levels and 27% (13 of 48) had sinking pre-beta lipoproteins. Contrasted with the IIa group, only 80% (32 of 40) of the IIb plasmas had detectable Lp(a) levels and 18% (7 of 40) had sinking pre-beta lipoprotein. In the type IV plasmas 78% (60 of 77) had detectable Lp(a) and 22% (17 of 77) had sinking pre-beta lipoprotein. Lp(a) or log Lp(a) levels were not correlated with apolipoprotein B levels (n = 485, r = 0.002 or 0.037, respectively). Furthermore, Lp(a) levels remained essentially constant in three subjects whose aprptein B levels were altered in response to pharmacological and/or dietary manipulation. A fourth subject had a 50% increase in Lp(a) but this change did not correlate with apoprotein B changes. Thus, these findings suggest that Lp(a) is metabolically independnet of low density lipoprotein even though it shares the same structural protein, apoprotein B."} {"id": "PMID:168456", "title": "Selective proteolysis of the receptor for parathyroid hormone in skeletal tissue.", "content": "Parathyroid hormone, calcitonin, and prostaglandin E2 activate the adenylate cyclase-cyclic AMP system in fetal-rat calvaria. These agents presumably interact with the tissue at separate receptor sites. When calvaria were preincubated with trypsin, 500 mug/ml for 45 min, the subsequent increase in 3',5'-AMP in response to parathyroid hormone was markedly diminished, whereas the response to calcitonin and prostaglandin E2 were not altered significantly. The effect was attributable to an action of the enzyme on the tissue and not to hydrolysis of the hormone. Similarily, preincubation of calvaria with trypsin prior to homogenization and preparation of a crude plasma membrane fraction decreased PTH-sensitive adenylate-cyclase activity by 58% but did not alter the degree of stimulation of the enzyme in response to calcitonin, prostaglandin E2, or sodium fluoride. These studies support the hypothesis that the actions of parathyroid hormone and calcitonin on bone are mediated through distinct receptor sites, and the receptors for parathyroid hormone can be altered selectively with trypsin.", "contents": "Selective proteolysis of the receptor for parathyroid hormone in skeletal tissue. Parathyroid hormone, calcitonin, and prostaglandin E2 activate the adenylate cyclase-cyclic AMP system in fetal-rat calvaria. These agents presumably interact with the tissue at separate receptor sites. When calvaria were preincubated with trypsin, 500 mug/ml for 45 min, the subsequent increase in 3',5'-AMP in response to parathyroid hormone was markedly diminished, whereas the response to calcitonin and prostaglandin E2 were not altered significantly. The effect was attributable to an action of the enzyme on the tissue and not to hydrolysis of the hormone. Similarily, preincubation of calvaria with trypsin prior to homogenization and preparation of a crude plasma membrane fraction decreased PTH-sensitive adenylate-cyclase activity by 58% but did not alter the degree of stimulation of the enzyme in response to calcitonin, prostaglandin E2, or sodium fluoride. These studies support the hypothesis that the actions of parathyroid hormone and calcitonin on bone are mediated through distinct receptor sites, and the receptors for parathyroid hormone can be altered selectively with trypsin."} {"id": "PMID:168477", "title": "The importance of geographical pathology.", "content": "Three different forms of cancer--the Burkitt lymphoma, nasopharyngeal carcinoma and skin cancer--are discussed in their relation to geographical distribution, the possible role of viruses, and genetic predisposition. Certain general conclusions in regard to cancer follow from these discussions. It is stated firmly that cancer is not a disease but a tissue manifestation which has not only many different presentations but also many different complex causes which consequently will need many different forms of treatment. A comparison of geographical differences is of immense value.", "contents": "The importance of geographical pathology. Three different forms of cancer--the Burkitt lymphoma, nasopharyngeal carcinoma and skin cancer--are discussed in their relation to geographical distribution, the possible role of viruses, and genetic predisposition. Certain general conclusions in regard to cancer follow from these discussions. It is stated firmly that cancer is not a disease but a tissue manifestation which has not only many different presentations but also many different complex causes which consequently will need many different forms of treatment. A comparison of geographical differences is of immense value."} {"id": "PMID:168478", "title": "Counter immunoelectrophoresis in rapid diagnosis of pox virus infections.", "content": "The use of the counter immunoelectrophoresis technique enhanced the reaction between vaccinia virus and its antibody. By means of 0.7% and 1% solutions of agarose, sharp, clear lines of precipitation were obtained within 30 minutes at 200 volts.", "contents": "Counter immunoelectrophoresis in rapid diagnosis of pox virus infections. The use of the counter immunoelectrophoresis technique enhanced the reaction between vaccinia virus and its antibody. By means of 0.7% and 1% solutions of agarose, sharp, clear lines of precipitation were obtained within 30 minutes at 200 volts."} {"id": "PMID:168481", "title": "[Spectacillin-a new-developed multi-effective penicillin in treating chronic bronchoulmonary diseases author's transl].", "content": "50 patients with a chronic disease of the bronchopulmonary system, within the therapy of an acute exacerbation received in addition to bronchosecretolytics, spasmolytic substances, and corticosterones the substance 'Spectacillin' in a dosage ranging from 2 to 6 grams per day during the period of 2 weeks. The acute exacerbation has been stopped in 34 patients and there-by the recurrence could be prevented. Although in 9 patients a clinical improvement has been obtained, no germ elimination could be ascertained; 7 cases of disease remained uninfluenced. The evalution is documentated by the clinical and laboratory findings, the germ analysis and the test of pulmonary functions. The compatibality can be evaluated as well-effective; especially the low rate of exanthema (2 patients) is to be emphasized.", "contents": "[Spectacillin-a new-developed multi-effective penicillin in treating chronic bronchoulmonary diseases author's transl]. 50 patients with a chronic disease of the bronchopulmonary system, within the therapy of an acute exacerbation received in addition to bronchosecretolytics, spasmolytic substances, and corticosterones the substance 'Spectacillin' in a dosage ranging from 2 to 6 grams per day during the period of 2 weeks. The acute exacerbation has been stopped in 34 patients and there-by the recurrence could be prevented. Although in 9 patients a clinical improvement has been obtained, no germ elimination could be ascertained; 7 cases of disease remained uninfluenced. The evalution is documentated by the clinical and laboratory findings, the germ analysis and the test of pulmonary functions. The compatibality can be evaluated as well-effective; especially the low rate of exanthema (2 patients) is to be emphasized."} {"id": "PMID:168482", "title": "A mammalian spot test: induction of genetic alterations in pigment cells of mouse embryos with x-rays and chemical mutagens.", "content": "Embroys heterozygous for five recessive coat-color genes from the cross C 57 BL/6 J Han x T-stock were x-irradiated with 100/r o r treated in utero with 50 mg/3 kg methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), respectively. Controls consisted of irradiated embryos of C 57 BL x C 57 BL matings homozygous wild-type for the genes under study, and non-treated offspring of both types of mating. The colors of the spots were observed in the adult fur were either due to expression of the recessive coat genes or were white. I. Irradiated and mutagen-treated offspring of C 57 BL x T-stock matings had almost exclusively nonwhite spots, distributed randomly over the mouse surface. 2. Irraidated offspring of C 57 BL x C 57 BL matings had only white spots which were always midventral. 3. In non-treated offspring of both types of mating no spot could be observed. After correcting for white midventral spots observed in the one type of control, the frequency of expression of one or the other of the recessive color genes is calculated to be about 11% for embryos irradiated with 100r or 101/2 days postconception, about 1% for embryos irradiated with 100r at 9 days postconception, about &% for embryos treated with 50 mg MMS/kg at 101/2 days postconception, and about 8% for embryos treated with 50 mg EMS/2 days postconception. It is discussed that the white midventral spots are preferentially the result of pigment cell killing, while the nonwhite spots are preferentially the result of gene mutations or recombinational processes like mitotic crossing over and mitotic gene conversion. Of numerical and structural chromosome aberrations only those come into question which are able to pass the filter of several mitoses. Therefore, the test system described is supposted to cover not only heitable DNA-alterations, but the whole spectrum of them.", "contents": "A mammalian spot test: induction of genetic alterations in pigment cells of mouse embryos with x-rays and chemical mutagens. Embroys heterozygous for five recessive coat-color genes from the cross C 57 BL/6 J Han x T-stock were x-irradiated with 100/r o r treated in utero with 50 mg/3 kg methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), respectively. Controls consisted of irradiated embryos of C 57 BL x C 57 BL matings homozygous wild-type for the genes under study, and non-treated offspring of both types of mating. The colors of the spots were observed in the adult fur were either due to expression of the recessive coat genes or were white. I. Irradiated and mutagen-treated offspring of C 57 BL x T-stock matings had almost exclusively nonwhite spots, distributed randomly over the mouse surface. 2. Irraidated offspring of C 57 BL x C 57 BL matings had only white spots which were always midventral. 3. In non-treated offspring of both types of mating no spot could be observed. After correcting for white midventral spots observed in the one type of control, the frequency of expression of one or the other of the recessive color genes is calculated to be about 11% for embryos irradiated with 100r or 101/2 days postconception, about 1% for embryos irradiated with 100r at 9 days postconception, about &% for embryos treated with 50 mg MMS/kg at 101/2 days postconception, and about 8% for embryos treated with 50 mg EMS/2 days postconception. It is discussed that the white midventral spots are preferentially the result of pigment cell killing, while the nonwhite spots are preferentially the result of gene mutations or recombinational processes like mitotic crossing over and mitotic gene conversion. Of numerical and structural chromosome aberrations only those come into question which are able to pass the filter of several mitoses. Therefore, the test system described is supposted to cover not only heitable DNA-alterations, but the whole spectrum of them."} {"id": "PMID:168483", "title": "Some aspects of the mechanism of action of steroid hormones.", "content": "Events related to the very early steps of steroid hormone action are reviewed, after a brief expos\u00e9 of the methods used for the measurement and calculation of protein-steroid interactions. A list of steroid binding plasma proteins is given, and their physiological variations and possible role(s) are discussed. The mechanism of entry of steroids into target cells is then considered especially the possibility of a protein mediated step. The metabolism of steroid hormone in target cells and its physiological significance are discussed, especially with reference to androgens in prostate, levator ani muscle and hypothalamus. No receptor of steroid hormone has yet been discovered if defined as the last entity with which the active steroid interacts before action is initiated. However, in the target tissues of steroid hormones, specific proteins have been detected (termed receptors) with properties that are compatible with an essential if not an obligatory role in steroid action. The properties ascribed to the cytosol receptors of different steroid hormones in various tissues, their binding properties, and their quantitative variations are reported. The transformation or activation of receptor after binding of the hormone is related to its transfer to the nucleus. The question posed by the recent observations on Non Histone Chromatin estrogen binding protein and of the \"insoluble\" nuclear receptor are discussed. Finally, a series of experiments are reviewed, dealing more specifically with the increase of protein and RNA synthesis in tissues in which steroids and RNA synthesis in tissues in which steroids promote growth (i.e. estradiol in uterus). The concept of a cascade phenomenon is reported, including the early synthesis of KIP (Key Intermediary Protein(s)) which would responsible for the secondary amplification of the response. It is discussed in connection with the present (and insufficient) knowledge of receptors and transcription machinery.", "contents": "Some aspects of the mechanism of action of steroid hormones. Events related to the very early steps of steroid hormone action are reviewed, after a brief expos\u00e9 of the methods used for the measurement and calculation of protein-steroid interactions. A list of steroid binding plasma proteins is given, and their physiological variations and possible role(s) are discussed. The mechanism of entry of steroids into target cells is then considered especially the possibility of a protein mediated step. The metabolism of steroid hormone in target cells and its physiological significance are discussed, especially with reference to androgens in prostate, levator ani muscle and hypothalamus. No receptor of steroid hormone has yet been discovered if defined as the last entity with which the active steroid interacts before action is initiated. However, in the target tissues of steroid hormones, specific proteins have been detected (termed receptors) with properties that are compatible with an essential if not an obligatory role in steroid action. The properties ascribed to the cytosol receptors of different steroid hormones in various tissues, their binding properties, and their quantitative variations are reported. The transformation or activation of receptor after binding of the hormone is related to its transfer to the nucleus. The question posed by the recent observations on Non Histone Chromatin estrogen binding protein and of the \"insoluble\" nuclear receptor are discussed. Finally, a series of experiments are reviewed, dealing more specifically with the increase of protein and RNA synthesis in tissues in which steroids and RNA synthesis in tissues in which steroids promote growth (i.e. estradiol in uterus). The concept of a cascade phenomenon is reported, including the early synthesis of KIP (Key Intermediary Protein(s)) which would responsible for the secondary amplification of the response. It is discussed in connection with the present (and insufficient) knowledge of receptors and transcription machinery."} {"id": "PMID:168487", "title": "Aerosol polymyxin and pneumonia in seriously ill patients.", "content": "Pneumonia caused by Pseudomonas aeruginosa occurs frequently in critically ill patients and is associated with a mortality rate of 70 per cent. An aerosol of polymyxin B was administered (2.5 mg per kilogram per day) to the upper airways of 292 patients in a respiratory-surgical intensive-care unit during a seven-month period, in an attempt to prevent Ps. aeruginosa pneumonia. Although only one of the patients studied acquired pneumonia due to Ps. aeruginosa, 10 others acquired pneumonia caused by a polymysinx-resistant organism. Seven pneumonias were caused by organisms not frequently pathogenic to man (flavobacteria, serratia and Streptococcus faecalis). The mortality rate for acquired pneumonia in this study, 64 per cent, is greater than that in previous studies in which either no polymyxin or cyclic polymyxin therapy was used. Continuous use of polymyxin B aerosol appears to be a dangerous form of therapy.", "contents": "Aerosol polymyxin and pneumonia in seriously ill patients. Pneumonia caused by Pseudomonas aeruginosa occurs frequently in critically ill patients and is associated with a mortality rate of 70 per cent. An aerosol of polymyxin B was administered (2.5 mg per kilogram per day) to the upper airways of 292 patients in a respiratory-surgical intensive-care unit during a seven-month period, in an attempt to prevent Ps. aeruginosa pneumonia. Although only one of the patients studied acquired pneumonia due to Ps. aeruginosa, 10 others acquired pneumonia caused by a polymysinx-resistant organism. Seven pneumonias were caused by organisms not frequently pathogenic to man (flavobacteria, serratia and Streptococcus faecalis). The mortality rate for acquired pneumonia in this study, 64 per cent, is greater than that in previous studies in which either no polymyxin or cyclic polymyxin therapy was used. Continuous use of polymyxin B aerosol appears to be a dangerous form of therapy."} {"id": "PMID:168488", "title": "Predominantly T-cell infiltrate in rheumatoid synovial membranes.", "content": "Lymphocytes infiltrating synovial membranes were characterized in eight patients with proliferative rheumatoid synovitis. Surface immunoglobulins were studied with use of immunofluorescence, and the C3 receptor was detected by adherence of red cells coated with antibody and complement - both are B-cell markers. Spontaneous rosette formation with sheep erythrocytes was used as a T-cell marker. To obtain viable lymphocytes in suspension, the villous synovium of five of these patients was digested with collagenase and deoxyribonuclease. Populations enriched in lymphocytes could be obtained by velocity sedimentation. Whereas only 9 to 35 per cent of lymphocytes bore surface immunoglobulins, the majority (70 to 85 per cent) formed sheep-erythrocyte rosettes. Cells bearing the C3 receptor constituted a distinct minority of synovial lymphocytes in frozen-tissue sections, and were found in follicle-like accumulations. These data indicate that the predominant infiltrating lymphocyte in proliferative rheumatoid synovitis is a T cell.", "contents": "Predominantly T-cell infiltrate in rheumatoid synovial membranes. Lymphocytes infiltrating synovial membranes were characterized in eight patients with proliferative rheumatoid synovitis. Surface immunoglobulins were studied with use of immunofluorescence, and the C3 receptor was detected by adherence of red cells coated with antibody and complement - both are B-cell markers. Spontaneous rosette formation with sheep erythrocytes was used as a T-cell marker. To obtain viable lymphocytes in suspension, the villous synovium of five of these patients was digested with collagenase and deoxyribonuclease. Populations enriched in lymphocytes could be obtained by velocity sedimentation. Whereas only 9 to 35 per cent of lymphocytes bore surface immunoglobulins, the majority (70 to 85 per cent) formed sheep-erythrocyte rosettes. Cells bearing the C3 receptor constituted a distinct minority of synovial lymphocytes in frozen-tissue sections, and were found in follicle-like accumulations. These data indicate that the predominant infiltrating lymphocyte in proliferative rheumatoid synovitis is a T cell."} {"id": "PMID:168490", "title": "Characterization of alpha1-antitrypsin in the inclusion bodies from the liver in alpha 1-antitrypsin deficiency.", "content": "alpha1-antitrypsin was isolated from periodic acid-Schiff-positive inclusion bodies from the hepatocytes of patients with alpha1-antitrypsin deficiency and further purified to enable more detailed chemical analysis. Amino acid and cyanogen bromide fragmentation studies showed a close similarity between hepatic and serum (PiMM) antitrypsin in contrast to the carbohydrate analysis, which revealed markedly deficient glycosylation of hepatic antitrypsin. A complete lack of sialic acid and a relative deficiency of all other carbohydrate components could fully explain the difference of approximately 6000 daltons in molecular size between the two proteins. The accumulation of hepatic globules is probably related to the physical properties of the defective antitrypsin, which include marked insolubility and tendency toward aggregation. The results strongly suggest an abnormal amino acid sequence in the peptide chain of the deficient antitrypsin. The interference with glycosylation may be related to steric hindrance.", "contents": "Characterization of alpha1-antitrypsin in the inclusion bodies from the liver in alpha 1-antitrypsin deficiency. alpha1-antitrypsin was isolated from periodic acid-Schiff-positive inclusion bodies from the hepatocytes of patients with alpha1-antitrypsin deficiency and further purified to enable more detailed chemical analysis. Amino acid and cyanogen bromide fragmentation studies showed a close similarity between hepatic and serum (PiMM) antitrypsin in contrast to the carbohydrate analysis, which revealed markedly deficient glycosylation of hepatic antitrypsin. A complete lack of sialic acid and a relative deficiency of all other carbohydrate components could fully explain the difference of approximately 6000 daltons in molecular size between the two proteins. The accumulation of hepatic globules is probably related to the physical properties of the defective antitrypsin, which include marked insolubility and tendency toward aggregation. The results strongly suggest an abnormal amino acid sequence in the peptide chain of the deficient antitrypsin. The interference with glycosylation may be related to steric hindrance."} {"id": "PMID:168493", "title": "Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease.", "content": "The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), \"atypical angina\" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients.", "contents": "Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease. The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), \"atypical angina\" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients."} {"id": "PMID:168504", "title": "Stimulation of adenosine 3',5'-monophosphate formation in guinea-pig cerebral cortical slices in a calcium free medium.", "content": "In guinea-pig cerebral cortical slices cyclic AMP concentrations increase during incubation with histamine+noradrenaline. After 10 min of incubation the levels of cyclic AMP start to decline. When calcium ions are omitted from the incubation medium, cyclic AMP levels do increase to a greater extent under the same conditions and do not drop during 30 min incubation. In the presence of calcium ions cyclic AMP synthesis can not be elicited by noradrenaline alone. In calcium-free Krebs-Ringer solution a pronounced effect of noradrenaline on cyclic AMP levels is observed. This effect of noradrenaline is shown to be mediated by a classical alpha-type receptor. 5-Hydroxytryptamine, prostaglandin E1 and dopamine do not significnatly enhance cyclic AMP formation in guinea-pig brain slices in either the presence in, or the absence of calcium ions from the incubation medium. Under depolarizing conditions of incubation the stimulatory effect of ouabain or 125 mM K+ is blocked in a calcium-free medium, while with the depolarizing agent veratridine no significant reduction of cyclic AMP formed during incubation in a calcium-free medium is obtained.", "contents": "Stimulation of adenosine 3',5'-monophosphate formation in guinea-pig cerebral cortical slices in a calcium free medium. In guinea-pig cerebral cortical slices cyclic AMP concentrations increase during incubation with histamine+noradrenaline. After 10 min of incubation the levels of cyclic AMP start to decline. When calcium ions are omitted from the incubation medium, cyclic AMP levels do increase to a greater extent under the same conditions and do not drop during 30 min incubation. In the presence of calcium ions cyclic AMP synthesis can not be elicited by noradrenaline alone. In calcium-free Krebs-Ringer solution a pronounced effect of noradrenaline on cyclic AMP levels is observed. This effect of noradrenaline is shown to be mediated by a classical alpha-type receptor. 5-Hydroxytryptamine, prostaglandin E1 and dopamine do not significnatly enhance cyclic AMP formation in guinea-pig brain slices in either the presence in, or the absence of calcium ions from the incubation medium. Under depolarizing conditions of incubation the stimulatory effect of ouabain or 125 mM K+ is blocked in a calcium-free medium, while with the depolarizing agent veratridine no significant reduction of cyclic AMP formed during incubation in a calcium-free medium is obtained."} {"id": "PMID:168505", "title": "[Electrical reaction of olfactory structure and the amygdaloid complex of the brain of dogs in a paradoxical stage of sleep].", "content": "Electrical activity of the olfactory bulb, olfactory tubercle amygdala, hippocampus, hypothalamus and neocortex during physiological sleep was studied in chronic experiments in unanesthetized unrestrained dogs;A synchronous high-frequency sinusoidal rhythm of 36-42 Hz was found in the amygdala and olfactory structures in the paradoxical phase of sleepmthis olfacto-amygdaloid rhythm, unlike that of aroused animals, was not the result of olfactory stimulation and persisted in dogs with trachael breathing; Its generation is probably of central origin; A comparison of the dynamics of this electrical activity with somatic, autonomic and teeg-correlates of sleep gives reasons to regard the olfacto-amygdaloid rhythm of 36-42 Hz as a specific EEG-correlate of the paradoxical sleep stage in dogs", "contents": "[Electrical reaction of olfactory structure and the amygdaloid complex of the brain of dogs in a paradoxical stage of sleep]. Electrical activity of the olfactory bulb, olfactory tubercle amygdala, hippocampus, hypothalamus and neocortex during physiological sleep was studied in chronic experiments in unanesthetized unrestrained dogs;A synchronous high-frequency sinusoidal rhythm of 36-42 Hz was found in the amygdala and olfactory structures in the paradoxical phase of sleepmthis olfacto-amygdaloid rhythm, unlike that of aroused animals, was not the result of olfactory stimulation and persisted in dogs with trachael breathing; Its generation is probably of central origin; A comparison of the dynamics of this electrical activity with somatic, autonomic and teeg-correlates of sleep gives reasons to regard the olfacto-amygdaloid rhythm of 36-42 Hz as a specific EEG-correlate of the paradoxical sleep stage in dogs"} {"id": "PMID:168514", "title": "Giant axonal neuropathy. A clinical entity affecting the central as well as the peripheral nervous system.", "content": "An 8-year-old girl had progressive muscle weakness and a unique posture of the lower limbs, areflexia, distal sensory impairment, and remarkably kinky hair. Histologic examination of the sural nerve showed giant axons filled with neurofilamentous masses. The clinical and histologic findings resembled those of recent cases reported as \"giant axonal neuropathy.\" Our patient's precocious puberty, Babinski's sign, and electroencephalographic abnormalities suggested central nervous system involvement. Two cases previously reported and the present one appear to represent a new clinical entity that affects the central and the peripheral nervous system.", "contents": "Giant axonal neuropathy. A clinical entity affecting the central as well as the peripheral nervous system. An 8-year-old girl had progressive muscle weakness and a unique posture of the lower limbs, areflexia, distal sensory impairment, and remarkably kinky hair. Histologic examination of the sural nerve showed giant axons filled with neurofilamentous masses. The clinical and histologic findings resembled those of recent cases reported as \"giant axonal neuropathy.\" Our patient's precocious puberty, Babinski's sign, and electroencephalographic abnormalities suggested central nervous system involvement. Two cases previously reported and the present one appear to represent a new clinical entity that affects the central and the peripheral nervous system."} {"id": "PMID:168520", "title": "\"Living cytology\" in the diagnosis of intraabdominal adenocarcinoma.", "content": "Cytologic diagnosis of adenocarcinoma metastatic to the peritoneal surface is often hampered by the difficulty of differentiating between reactive mesothelial cells and macrophages from malignant epithelial cells by light microscopy. With in vitro tissue culture technics, the fibroblastic dedifferentiation of mesothelial cells facilitates the recognition of residual neoplastic epithelial cells. Ascitic fliid from 18 patients who ultimately had histologic documentation of intraabdominal adenocarcinomatosis was studied by tissue culture technics. In 15 of the 18 patients, small islets of replicating tumor cells could be identified after the mesothelial cells had dedifferentiated into fibroblasts. With one exception the average time between collection of the specimen and recognition of adenocarcinoma was 6 days. In 14 cases, a definitive diagnosis of malignancy was made by cytologic analysis.", "contents": "\"Living cytology\" in the diagnosis of intraabdominal adenocarcinoma. Cytologic diagnosis of adenocarcinoma metastatic to the peritoneal surface is often hampered by the difficulty of differentiating between reactive mesothelial cells and macrophages from malignant epithelial cells by light microscopy. With in vitro tissue culture technics, the fibroblastic dedifferentiation of mesothelial cells facilitates the recognition of residual neoplastic epithelial cells. Ascitic fliid from 18 patients who ultimately had histologic documentation of intraabdominal adenocarcinomatosis was studied by tissue culture technics. In 15 of the 18 patients, small islets of replicating tumor cells could be identified after the mesothelial cells had dedifferentiated into fibroblasts. With one exception the average time between collection of the specimen and recognition of adenocarcinoma was 6 days. In 14 cases, a definitive diagnosis of malignancy was made by cytologic analysis."} {"id": "PMID:168521", "title": "Cervical carcinogenesis with herpes simplex virus, type 2.", "content": "In the past few years there have been a number of reports correlating a high frequency of herpes simplex virus type 2(HSV-2) infection with lesions of the uterine cervix. These studies have used a clinical history of herpetic infection or the demonstration of herpetic antibodies in the cancer patients. The present study was performed to evaluate any possible carcinogenic activity of the formalin-inoculated herpes simplex virus type 2 in the reproductive tract of the female mouse. This approach to the study was selected because of previous experience with a model system of carcinogenesis of the cervix uteri using coal tar hydrocarbons. Cytologic and histologic preparations from experimental animals and controls are presented to demonstrate the mucosal alterations and tumors observed in the animals. Noninvasive lesions of the cervix were identified in 76.8% and invasive adenocarcinoma detected in 30.2% of the mice.", "contents": "Cervical carcinogenesis with herpes simplex virus, type 2. In the past few years there have been a number of reports correlating a high frequency of herpes simplex virus type 2(HSV-2) infection with lesions of the uterine cervix. These studies have used a clinical history of herpetic infection or the demonstration of herpetic antibodies in the cancer patients. The present study was performed to evaluate any possible carcinogenic activity of the formalin-inoculated herpes simplex virus type 2 in the reproductive tract of the female mouse. This approach to the study was selected because of previous experience with a model system of carcinogenesis of the cervix uteri using coal tar hydrocarbons. Cytologic and histologic preparations from experimental animals and controls are presented to demonstrate the mucosal alterations and tumors observed in the animals. Noninvasive lesions of the cervix were identified in 76.8% and invasive adenocarcinoma detected in 30.2% of the mice."} {"id": "PMID:168522", "title": "Paget's disease of the vulva and carcinoma of the breast.", "content": "Vulvar Paget's disease is an intraepithelial change which is locally recurrent and has minimal if any propensity to invasion. Its major significance lies in the frequency with which concomitant carcinomas are discovered in association with the vulvar skin lesion. Adenocarcinoma of the vulvar apocrine glands is the most commonly associated tumor. Another apocrine adenocarcinoma, carcinoma of the breast, either antecedent or concomitant, is the second most frequently associated tumor, having been noted in 14 cases of vulvar Paget's disease. A case report illustrating this association is presented, and the importance of preoperative breast screening procedures in all patients with vulvar Paget's disease is demonstrated.", "contents": "Paget's disease of the vulva and carcinoma of the breast. Vulvar Paget's disease is an intraepithelial change which is locally recurrent and has minimal if any propensity to invasion. Its major significance lies in the frequency with which concomitant carcinomas are discovered in association with the vulvar skin lesion. Adenocarcinoma of the vulvar apocrine glands is the most commonly associated tumor. Another apocrine adenocarcinoma, carcinoma of the breast, either antecedent or concomitant, is the second most frequently associated tumor, having been noted in 14 cases of vulvar Paget's disease. A case report illustrating this association is presented, and the importance of preoperative breast screening procedures in all patients with vulvar Paget's disease is demonstrated."} {"id": "PMID:168523", "title": "Liver tumors in women on contraceptive steroids.", "content": "The possible association between oral contraceptives and benign liver tumors has recently been reported. To date the majority of cases have been diagnosed as benign hepatomas (liver cell adenomas). We have had the opportunity to study 13 such cases. Eight have been examples of focal nodular hyperplasia of the liver; however, in addition, there were examples of hepatocellular carcinoma, liver cell adenoma, and possible liver cell hamartoma; all were in women on \"the pill.\" Gynecologists are alerted to the fact that many of the patients present with symptoms of acute abdomen, syncope or shock, and intrahepatic or intraperitoneal bleeding. Prompt diagnosis and treatment may be lifesaving.", "contents": "Liver tumors in women on contraceptive steroids. The possible association between oral contraceptives and benign liver tumors has recently been reported. To date the majority of cases have been diagnosed as benign hepatomas (liver cell adenomas). We have had the opportunity to study 13 such cases. Eight have been examples of focal nodular hyperplasia of the liver; however, in addition, there were examples of hepatocellular carcinoma, liver cell adenoma, and possible liver cell hamartoma; all were in women on \"the pill.\" Gynecologists are alerted to the fact that many of the patients present with symptoms of acute abdomen, syncope or shock, and intrahepatic or intraperitoneal bleeding. Prompt diagnosis and treatment may be lifesaving."} {"id": "PMID:168524", "title": "Viral replication in human ovarian cell culture.", "content": "A method is presented for the preparation and maintenance of human ovarian cell cultures. Sections of normal ovaries removed at surgery were minced, trypsinized, and seeded as cell cultures grown in minimal essential media at 37 C. Long-term, low-passage cultures were grown in quantities sufficient to permit viral studies. Ovarian cells, of passage 23, were challenged with 57 known viruses. Of these viruses, 52 (especially viruses of the picornavirus and adenovirus groups) produced typical cytopathic effects. The significance of these studies is discussed.", "contents": "Viral replication in human ovarian cell culture. A method is presented for the preparation and maintenance of human ovarian cell cultures. Sections of normal ovaries removed at surgery were minced, trypsinized, and seeded as cell cultures grown in minimal essential media at 37 C. Long-term, low-passage cultures were grown in quantities sufficient to permit viral studies. Ovarian cells, of passage 23, were challenged with 57 known viruses. Of these viruses, 52 (especially viruses of the picornavirus and adenovirus groups) produced typical cytopathic effects. The significance of these studies is discussed."} {"id": "PMID:168526", "title": "Murine tumor induction by cytomegalovirus.", "content": "Cytomegalic inclusion disease can be induced in mice with relative ease. In the study reported here, grandular neoplasms were produced in four mice by means of immunosupression together with large doses of cytomegalovirus. The results of this study suggest that cytomegalovirus may well be an etiologic agent in the formation of salivary gland tumors.", "contents": "Murine tumor induction by cytomegalovirus. Cytomegalic inclusion disease can be induced in mice with relative ease. In the study reported here, grandular neoplasms were produced in four mice by means of immunosupression together with large doses of cytomegalovirus. The results of this study suggest that cytomegalovirus may well be an etiologic agent in the formation of salivary gland tumors."} {"id": "PMID:168529", "title": "Peritonsillolith.", "content": "Peritonsillolith appears to be an unknown entity. Two cases of lithiasis in the peritonsillar region following spontaneous rupture of peritonsillar abscesses have been reported. The authors have speculated concerning the cause of stone formation in the peritonsillar region, which has been designated \"peritonsillolith,\" on the basis of lithiasis in other regions of the body, such as gallbladder, kidneys, and salivary glands. Peritonsilloliths most likely form as a result of incomplete evacuation of pus, the dead bacteria and the pus cells providing the nidus for their formation. The salts of these stones are undoubtedly derived from the inflammatory exudates and saliva.", "contents": "Peritonsillolith. Peritonsillolith appears to be an unknown entity. Two cases of lithiasis in the peritonsillar region following spontaneous rupture of peritonsillar abscesses have been reported. The authors have speculated concerning the cause of stone formation in the peritonsillar region, which has been designated \"peritonsillolith,\" on the basis of lithiasis in other regions of the body, such as gallbladder, kidneys, and salivary glands. Peritonsilloliths most likely form as a result of incomplete evacuation of pus, the dead bacteria and the pus cells providing the nidus for their formation. The salts of these stones are undoubtedly derived from the inflammatory exudates and saliva."} {"id": "PMID:168530", "title": "The central odontogenic fibroma. Clinical and morphologic studies.", "content": "The clinical, pathologic, and ultrastructural features and pertinent case history of an 11-year-old boy with a rare benign odontogenic neoplasm, the central odontogenic fibroma, are presented. A review of the literature reveals seven other lesions with clinical and pathologic findings similar to those of this case. This study supports the concept that the central odontogenic fibroma is a distinct odontogenic neoplasm of bone which occurs most commonly in the mandible as a multilocular, radiolucent, and slowly growing expansile lesion with no tendency to recur after surgical enucleation. The ultrastructural findings indicate that the central odontogenic fibroma and the odontogenic myxoma share many common morphologic features and have an apparently similar histogenesis.", "contents": "The central odontogenic fibroma. Clinical and morphologic studies. The clinical, pathologic, and ultrastructural features and pertinent case history of an 11-year-old boy with a rare benign odontogenic neoplasm, the central odontogenic fibroma, are presented. A review of the literature reveals seven other lesions with clinical and pathologic findings similar to those of this case. This study supports the concept that the central odontogenic fibroma is a distinct odontogenic neoplasm of bone which occurs most commonly in the mandible as a multilocular, radiolucent, and slowly growing expansile lesion with no tendency to recur after surgical enucleation. The ultrastructural findings indicate that the central odontogenic fibroma and the odontogenic myxoma share many common morphologic features and have an apparently similar histogenesis."} {"id": "PMID:168531", "title": "Congenital granular-cell tumor of alveolar ridge and tongue. Report of two cases.", "content": "Granular-cell tumors in the oral cavity occur primarily on the tongue (myoblastoma) in adults and on the gum pads (congenital epulis) in infants. Because of the usual location and age, these histologically and histochemically similar tumors have been separate clinical entities. These case reports, however, report the concurrence of both clinical entities in the same patient. A 7-day-old female infant had a 1 cm. epulis on the right anterior maxilla and two 1.5 mm. masses on the anterior ventrum of the tongue. A 12-day-old girl had a 1 cm. epulis on the anterior mandible and two 1.5 mm. masses on the anterior tongue near the tip. In both cases, all lesions were histologically and histochemically similar and were granular-cell tumors. This suggests a relationship in the origin of these entities and tends to rule out an odontogenic origin for the epulis.", "contents": "Congenital granular-cell tumor of alveolar ridge and tongue. Report of two cases. Granular-cell tumors in the oral cavity occur primarily on the tongue (myoblastoma) in adults and on the gum pads (congenital epulis) in infants. Because of the usual location and age, these histologically and histochemically similar tumors have been separate clinical entities. These case reports, however, report the concurrence of both clinical entities in the same patient. A 7-day-old female infant had a 1 cm. epulis on the right anterior maxilla and two 1.5 mm. masses on the anterior ventrum of the tongue. A 12-day-old girl had a 1 cm. epulis on the anterior mandible and two 1.5 mm. masses on the anterior tongue near the tip. In both cases, all lesions were histologically and histochemically similar and were granular-cell tumors. This suggests a relationship in the origin of these entities and tends to rule out an odontogenic origin for the epulis."} {"id": "PMID:168532", "title": "Shock synthesis of amino acids II.", "content": "The synthesis of amino acids behind shock waves in methane, ethane, ammonia, and water vapor was further investigated. Aldehydes and HCN are formed separately in the non-homogeneous gas during the high temperature period and recombine with ammonia during the thermal quench period, to form chi-amino nitriles. The chi-amino nitriles are either hydrolyzed by excess water vapor during the quench period or emerge as such after the reaction is completed. A combined gas chromatograph-mass spectrometer analysis of the reaction product showed identical amounts of D and L amino acids, thus confirming the absence of contaminants. Thunder shock waves were shown to be a suitable source of energy for the production of amino acids.", "contents": "Shock synthesis of amino acids II. The synthesis of amino acids behind shock waves in methane, ethane, ammonia, and water vapor was further investigated. Aldehydes and HCN are formed separately in the non-homogeneous gas during the high temperature period and recombine with ammonia during the thermal quench period, to form chi-amino nitriles. The chi-amino nitriles are either hydrolyzed by excess water vapor during the quench period or emerge as such after the reaction is completed. A combined gas chromatograph-mass spectrometer analysis of the reaction product showed identical amounts of D and L amino acids, thus confirming the absence of contaminants. Thunder shock waves were shown to be a suitable source of energy for the production of amino acids."} {"id": "PMID:168533", "title": "Quantum chemical study of the thermodynamics, kinetics of formation and bonding of H2CN: relevance to prebiotic chemistry.", "content": "Using the Iterative Extended Huckel Theory (IEHT), energy-conformation studies have been carried out for H2CN (I), trans-HCNH (IIA), and cis-HCNH (IIB), three possible isomers formed by addition of a hydrogen atom to hydrogen cyanide. Calculations show that the order of decreasing thermodynamic stability is I greater than IIA greater than IIB. Additionally, from calculated energies along simulated reaction pathways, the formation of I from HCN+H appears to be kinetically favored over IIA. Calculated properties of the minimum energy conformers of I and IIA are described and the potential role of H2CN (I) as a reactive intermediate in prebiotic organic synthesis and its possible relevance to interstellar organic chemistry are discussed.", "contents": "Quantum chemical study of the thermodynamics, kinetics of formation and bonding of H2CN: relevance to prebiotic chemistry. Using the Iterative Extended Huckel Theory (IEHT), energy-conformation studies have been carried out for H2CN (I), trans-HCNH (IIA), and cis-HCNH (IIB), three possible isomers formed by addition of a hydrogen atom to hydrogen cyanide. Calculations show that the order of decreasing thermodynamic stability is I greater than IIA greater than IIB. Additionally, from calculated energies along simulated reaction pathways, the formation of I from HCN+H appears to be kinetically favored over IIA. Calculated properties of the minimum energy conformers of I and IIA are described and the potential role of H2CN (I) as a reactive intermediate in prebiotic organic synthesis and its possible relevance to interstellar organic chemistry are discussed."} {"id": "PMID:168534", "title": "Macromolecules and the origin of life.", "content": "From our knowledge of present day organisms, it is hard to imagine a living assembly, even at its most primitive stage, without macromolecules. In order to look for the macromolecules which possibly participated in the assembly of the primitive organisms, the reaction and formation of polymers in HCN under irradiation of ultraviolet ray of 184.9 nm. was studied. As an example of a simple way of producing an assembly of macromolecules, the mechanism of coacrevation was studied by using gelatin as the material.", "contents": "Macromolecules and the origin of life. From our knowledge of present day organisms, it is hard to imagine a living assembly, even at its most primitive stage, without macromolecules. In order to look for the macromolecules which possibly participated in the assembly of the primitive organisms, the reaction and formation of polymers in HCN under irradiation of ultraviolet ray of 184.9 nm. was studied. As an example of a simple way of producing an assembly of macromolecules, the mechanism of coacrevation was studied by using gelatin as the material."} {"id": "PMID:168535", "title": "The origin of proteins: Heteropolypeptides from hydrogen cyanide and water.", "content": "Evidence from laboratory and extraterrestrial chemistry is presented consistent with the hypothesis that the original heteropolypeptides on Earth were synthesized spontaneously from hydrogen cyanide and water without the intervening formation of chi-amino acids, a key step being the direct polymerization of atmospheric hydrogen cyanide to polyaminomalononitrile (IV) via dimeric HCN. Molecular orbital calculations (INDO) show that the most probable structure for (HCN)2 is azacyclopropenylidenimine. Successive reactions of hydrogen cyanide with the reactive nitrile side chains of IV then yield heteropolyamidines which are converted by water to heteropolypeptides. To study this postulated modification of a homopolymer to a heteropolymer, poly-chi-cyanoglycine (IX) was prepared from the N-carboxyanhydride of chi-cyanoglycine. Hydrolysis of IX, a polyamide analog of the polyamidine IV, yielded glycine. However, when IX was hydrolysed after being treated with hydrogen cyanide, other chi-amino acids were also obtained including alanine, serine, aspartic acid and glutamic acid, suggesting that the nitrile groups of IX (and therfore of IV) are indeed readily attacked by hydrogen cyanide as predicted. Further theoretical and experimental studies support the view that hydrogen cyanide polymerization along these lines is a universal process that accounts not only for the past formation of primitive proteins on Earth, but also for the yellow-brown-orange colors of Jupiter today and for the presence of water-soluble compounds hydrolyzable to chi-amino acids in materials obtained from environments as diverse as the moon, carbonaceous chondrites and the reaction chambers used to simulate organic synthesis in planetary atmospheres.", "contents": "The origin of proteins: Heteropolypeptides from hydrogen cyanide and water. Evidence from laboratory and extraterrestrial chemistry is presented consistent with the hypothesis that the original heteropolypeptides on Earth were synthesized spontaneously from hydrogen cyanide and water without the intervening formation of chi-amino acids, a key step being the direct polymerization of atmospheric hydrogen cyanide to polyaminomalononitrile (IV) via dimeric HCN. Molecular orbital calculations (INDO) show that the most probable structure for (HCN)2 is azacyclopropenylidenimine. Successive reactions of hydrogen cyanide with the reactive nitrile side chains of IV then yield heteropolyamidines which are converted by water to heteropolypeptides. To study this postulated modification of a homopolymer to a heteropolymer, poly-chi-cyanoglycine (IX) was prepared from the N-carboxyanhydride of chi-cyanoglycine. Hydrolysis of IX, a polyamide analog of the polyamidine IV, yielded glycine. However, when IX was hydrolysed after being treated with hydrogen cyanide, other chi-amino acids were also obtained including alanine, serine, aspartic acid and glutamic acid, suggesting that the nitrile groups of IX (and therfore of IV) are indeed readily attacked by hydrogen cyanide as predicted. Further theoretical and experimental studies support the view that hydrogen cyanide polymerization along these lines is a universal process that accounts not only for the past formation of primitive proteins on Earth, but also for the yellow-brown-orange colors of Jupiter today and for the presence of water-soluble compounds hydrolyzable to chi-amino acids in materials obtained from environments as diverse as the moon, carbonaceous chondrites and the reaction chambers used to simulate organic synthesis in planetary atmospheres."} {"id": "PMID:168536", "title": "Prebiotic nucleotide synthesis-demonstration of a geologically plausible pathway.", "content": "Mineral phosphate (apatite) is activated for the synthesis of nucleotides when dilute solutions containing nucleoside and ammonium oxalate are evaporated in its presence. A natural, igneous fluorapatite was found to be even more effective in nucleotide synthesis than the more soluble hydroxylapatite. The phosphorylation is considerably more efficient if urea of cyanamide is also present. Hydrolysis of solutions of cyanogen to form oxalate and urea among other products is a spontaneous process that provides a geologically plausible model for necleotide synthesis on the primitive earth.", "contents": "Prebiotic nucleotide synthesis-demonstration of a geologically plausible pathway. Mineral phosphate (apatite) is activated for the synthesis of nucleotides when dilute solutions containing nucleoside and ammonium oxalate are evaporated in its presence. A natural, igneous fluorapatite was found to be even more effective in nucleotide synthesis than the more soluble hydroxylapatite. The phosphorylation is considerably more efficient if urea of cyanamide is also present. Hydrolysis of solutions of cyanogen to form oxalate and urea among other products is a spontaneous process that provides a geologically plausible model for necleotide synthesis on the primitive earth."} {"id": "PMID:168537", "title": "Models of prebiological phosphorylation.", "content": "The hypothesis that contemporary metabolic pathways envolved from analogous chemical reaction sequences on the primitive Earth leads to a reexamination of models of prebiological phosphorylation. Present-day phosphate uptake by algae and bacteria seems to involve two transport systems: (a) A n active transport process occurring at low external phosphate concentrations (as in umpolluted natural waters), with a transport constant Ks of 10(-7) to 10(-6) M Pi. (b) Another (probably diffusive) process at higher phosphate concentrations (greater than 10-6 M)(as in the interstitial water of reducing sediments). Laboratory model experiments are described for the reation of reducing sugars with orthophosphate in the presence of cyanogen, producing glycosyl phosphates. These reactions proceed with appreciable yields only at high phosphate concentrations (greater than 10-3 M), and may thus possibly serve as simulations of prebiological phosphorylation with diffusive transport, as it may have occurred in the intestial water of reducing sediments.", "contents": "Models of prebiological phosphorylation. The hypothesis that contemporary metabolic pathways envolved from analogous chemical reaction sequences on the primitive Earth leads to a reexamination of models of prebiological phosphorylation. Present-day phosphate uptake by algae and bacteria seems to involve two transport systems: (a) A n active transport process occurring at low external phosphate concentrations (as in umpolluted natural waters), with a transport constant Ks of 10(-7) to 10(-6) M Pi. (b) Another (probably diffusive) process at higher phosphate concentrations (greater than 10-6 M)(as in the interstitial water of reducing sediments). Laboratory model experiments are described for the reation of reducing sugars with orthophosphate in the presence of cyanogen, producing glycosyl phosphates. These reactions proceed with appreciable yields only at high phosphate concentrations (greater than 10-3 M), and may thus possibly serve as simulations of prebiological phosphorylation with diffusive transport, as it may have occurred in the intestial water of reducing sediments."} {"id": "PMID:168538", "title": "Evolution of photosystems of photosynthetic organisms.", "content": "It is generally accepted that two photosystems function successively in photosynthetic electron transport chain of plants and algae. The interaction of these photosystems results in the enhancement of photosynthesis. It was suggested that only one photosystem is present in purple bacteria, the most primitive photosynthetic organisms. The functioning of this photosystem is accompanied by absorption changes at 890 nm. Recently new spectral changes were found in Chramatium chromatophores under reductive conditions, more favorable for bacterial growth. Some of that spectral changes take place even at liquid nitrogen temperature. It is proposed these absorption changes could be related to other photosystem functioning in low potential region. Such a photosystem is necessary for reduction of NAD in Chromatium, for which the reverse electron transport to NAD was not shown. In contrast to photosystems of plants, the bacterial photosystems appear to function independently because the enhancement of bacterial photosynthesis is not found. Apparently the evolution of photosystems involved interaction between independent photosystmes, one of them functioning under more oxidative conditions.", "contents": "Evolution of photosystems of photosynthetic organisms. It is generally accepted that two photosystems function successively in photosynthetic electron transport chain of plants and algae. The interaction of these photosystems results in the enhancement of photosynthesis. It was suggested that only one photosystem is present in purple bacteria, the most primitive photosynthetic organisms. The functioning of this photosystem is accompanied by absorption changes at 890 nm. Recently new spectral changes were found in Chramatium chromatophores under reductive conditions, more favorable for bacterial growth. Some of that spectral changes take place even at liquid nitrogen temperature. It is proposed these absorption changes could be related to other photosystem functioning in low potential region. Such a photosystem is necessary for reduction of NAD in Chromatium, for which the reverse electron transport to NAD was not shown. In contrast to photosystems of plants, the bacterial photosystems appear to function independently because the enhancement of bacterial photosynthesis is not found. Apparently the evolution of photosystems involved interaction between independent photosystmes, one of them functioning under more oxidative conditions."} {"id": "PMID:168543", "title": "Hormonal control of glucose metabolism.", "content": "Glucose homeostasis is accomplished through two major hormones, glucagon and insulin. These hormones, of course, must work in concert with other permissive hormones such as glucocorticoids and catecholamines to bring about a multiplicity of physiological processes such as gluconeogenesis, glycolysis, lipolysis, and proteolysis that maintain the organism's biochemical integrity.", "contents": "Hormonal control of glucose metabolism. Glucose homeostasis is accomplished through two major hormones, glucagon and insulin. These hormones, of course, must work in concert with other permissive hormones such as glucocorticoids and catecholamines to bring about a multiplicity of physiological processes such as gluconeogenesis, glycolysis, lipolysis, and proteolysis that maintain the organism's biochemical integrity."} {"id": "PMID:168544", "title": "[The effect of asbestos cement, UICC asbestos samples and quartz on the peritoneum of the mouse].", "content": "Aqueous suspensions of asbestos cement powder injected experimentally into the peritoneal cavity of mice act as a fibrogenic agent, as do chrysotile asbestos or chrysotile asbestos-containing soil samples. The fibrotic nodules caused by the dust resemble morphologically silicosis granulomas. In addition, asbestos cement has a characteristically strong cytotoxic effect during the first 2 weeks of the experiment. It is suggested that this is due to the chrysotile asbestos and/or the calcite component of the powder. Amosite and crocidolite, on the other hand, induce a diffuse peritoneal fibrosis with the appearance of numerous foreign body giant cells and asbestos bodies. Dust particles displaced to the regional lymph nodes are frequent in the animals treated with quartz, asbestos cement and asbestos-containing soil samples. A spindle cell type sarcoma arising from the visceral peritoneum is observed in animals injected with crocidolite or asbestos cement. In addition, dusts containing chrysotile asbestos induce considerable amyloidosis of the liver and spleen.", "contents": "[The effect of asbestos cement, UICC asbestos samples and quartz on the peritoneum of the mouse]. Aqueous suspensions of asbestos cement powder injected experimentally into the peritoneal cavity of mice act as a fibrogenic agent, as do chrysotile asbestos or chrysotile asbestos-containing soil samples. The fibrotic nodules caused by the dust resemble morphologically silicosis granulomas. In addition, asbestos cement has a characteristically strong cytotoxic effect during the first 2 weeks of the experiment. It is suggested that this is due to the chrysotile asbestos and/or the calcite component of the powder. Amosite and crocidolite, on the other hand, induce a diffuse peritoneal fibrosis with the appearance of numerous foreign body giant cells and asbestos bodies. Dust particles displaced to the regional lymph nodes are frequent in the animals treated with quartz, asbestos cement and asbestos-containing soil samples. A spindle cell type sarcoma arising from the visceral peritoneum is observed in animals injected with crocidolite or asbestos cement. In addition, dusts containing chrysotile asbestos induce considerable amyloidosis of the liver and spleen."} {"id": "PMID:168545", "title": "Influence of sex and sex hormones on transplantable hepatocellular carcinoma in the rat.", "content": "Palpable subcutaneous transplants of hepatocellular carcinoma-35 appeared slightly earlier in male animals; however, the number of successful growths was no greater than that in female animals. Castration and administration of testosterone or diethylstilbestrol were performed after the transplants reached 1.0-1.5 cm in size. The carcinoma was less well differentiated histologically, had more bile pigment, grew rapidly, mestastasized sooner and killed the host quickly in castrated females given testosterone propionate. Bile was present in lung metastases. There was little difference in the growth rate in intact or castrated male or female animals. Exogenous diethylstilbestrol slowed the growth of the transplants and cause weight loss in castrated males. The weight loss was felt to be related to extensive necrosis of the carcinoma.", "contents": "Influence of sex and sex hormones on transplantable hepatocellular carcinoma in the rat. Palpable subcutaneous transplants of hepatocellular carcinoma-35 appeared slightly earlier in male animals; however, the number of successful growths was no greater than that in female animals. Castration and administration of testosterone or diethylstilbestrol were performed after the transplants reached 1.0-1.5 cm in size. The carcinoma was less well differentiated histologically, had more bile pigment, grew rapidly, mestastasized sooner and killed the host quickly in castrated females given testosterone propionate. Bile was present in lung metastases. There was little difference in the growth rate in intact or castrated male or female animals. Exogenous diethylstilbestrol slowed the growth of the transplants and cause weight loss in castrated males. The weight loss was felt to be related to extensive necrosis of the carcinoma."} {"id": "PMID:168546", "title": "Rhinosporidium seeberi: spherules and their significance.", "content": "This study of the nature and functional significance of the spherules that develop in sporoblasts show them to participate in the germination of Rhinosporidium seeberi and are the precursors of the trophocytes.", "contents": "Rhinosporidium seeberi: spherules and their significance. This study of the nature and functional significance of the spherules that develop in sporoblasts show them to participate in the germination of Rhinosporidium seeberi and are the precursors of the trophocytes."} {"id": "PMID:168539", "title": "Photochemical synthesis of simple organic free radicals on simulated planteary surfaces-an ESR study.", "content": "Electron spin resonance spectroscopy provided evidence for formation of hydroxyl radicals during ultraviolet photolysis (254 nm) at -170C of H2O adsorbed on silica gel or of silica gel alone. The carboxyl radical was observed when CO or CO2 or a mixture of CO and CO2 absorbed on silica gel at -170C was irradiated. The ESR signals of these radicals slowly disappeared when the irradiated samples were warmed to room temperature. However, re-irradiation of CO or CO2, or the mixture CO and CO2 on silica gel at room temperature then produced a new species, the carbon dioxide anion radical, which slowly decayed and which was identical with that produced by direct photolysis of formic acid adsorbed on silica gel. The primary photochemical process may involve formation of hydrogen and hydroxyl radicals by means of (1) photodissociation of H2O physically adsorbed on the silica gel, or (2) absorption of the excitation energy by the silica gel surface with subsequent cleavage of the silanol bonds, or (3) dissociation of H2O molecules throug photosensitization by the surfaces or a combination of (1) to (3). Subsequent reactions of these radicals with adsorbed CO or CO2 or both yield carboxyl radicals, CO2H, the precsursors of formic acid. Our results confirm the formation of formic acid under simulated Martian conditions and provide a mechanistic basis for gauging the potential importance of gas-solid photochemistry for chemical evolution on other extraterrestrial bodies, on the primitive earth and on dust grains in the interstellar medium.", "contents": "Photochemical synthesis of simple organic free radicals on simulated planteary surfaces-an ESR study. Electron spin resonance spectroscopy provided evidence for formation of hydroxyl radicals during ultraviolet photolysis (254 nm) at -170C of H2O adsorbed on silica gel or of silica gel alone. The carboxyl radical was observed when CO or CO2 or a mixture of CO and CO2 absorbed on silica gel at -170C was irradiated. The ESR signals of these radicals slowly disappeared when the irradiated samples were warmed to room temperature. However, re-irradiation of CO or CO2, or the mixture CO and CO2 on silica gel at room temperature then produced a new species, the carbon dioxide anion radical, which slowly decayed and which was identical with that produced by direct photolysis of formic acid adsorbed on silica gel. The primary photochemical process may involve formation of hydrogen and hydroxyl radicals by means of (1) photodissociation of H2O physically adsorbed on the silica gel, or (2) absorption of the excitation energy by the silica gel surface with subsequent cleavage of the silanol bonds, or (3) dissociation of H2O molecules throug photosensitization by the surfaces or a combination of (1) to (3). Subsequent reactions of these radicals with adsorbed CO or CO2 or both yield carboxyl radicals, CO2H, the precsursors of formic acid. Our results confirm the formation of formic acid under simulated Martian conditions and provide a mechanistic basis for gauging the potential importance of gas-solid photochemistry for chemical evolution on other extraterrestrial bodies, on the primitive earth and on dust grains in the interstellar medium."} {"id": "PMID:168547", "title": "Malakoplakia of the prostate: a morphological and biochemical study.", "content": "A case of malakoplakia of the prostate is presented. Electron microscopic appearances support the origin of the Michaelis-Gutmann bodies from phagolysosomes in the histiocytes characteristic of the lesion. Biochemical analysis revealed the presence of muramic acid in the prostate with malakoplakia. This amino sugar is characteristic of bacterial cell walls and despite the absence of demonstrable bacteria in the affected tissues indicates the involvement of bacteria in the disease process.", "contents": "Malakoplakia of the prostate: a morphological and biochemical study. A case of malakoplakia of the prostate is presented. Electron microscopic appearances support the origin of the Michaelis-Gutmann bodies from phagolysosomes in the histiocytes characteristic of the lesion. Biochemical analysis revealed the presence of muramic acid in the prostate with malakoplakia. This amino sugar is characteristic of bacterial cell walls and despite the absence of demonstrable bacteria in the affected tissues indicates the involvement of bacteria in the disease process."} {"id": "PMID:168540", "title": "High frequency discharge experiment. I: Formation of organic compounds from methane and ammonia.", "content": "Investigations of the synthesis of organic compounds from methane and ammonia were carried out by using high frequency discharges. The radical of CN was observed in the early phase of the discharge. Therefore it is considered that the CN radical contributes to the successive reaction steps. An important intermediate, a tetramer of hydrogen cyanide was observed to be formed at room temperature. The amounts of this compound progressively increased with time. It was speculated that the purines which were identified in the refluxed sample were synthesized through the above tetramer. Compounds which are thought to be heterocyclic (max:250-265nm) were initially formed in the sample trapped at liquid nitrogen temperature. After hydrolysis with hydrochloric acid, Gly, Asp Ala, etc. were observed in the sample. Overall yield of organic compounds was estimates at 5-6% based on input carbon of methane.", "contents": "High frequency discharge experiment. I: Formation of organic compounds from methane and ammonia. Investigations of the synthesis of organic compounds from methane and ammonia were carried out by using high frequency discharges. The radical of CN was observed in the early phase of the discharge. Therefore it is considered that the CN radical contributes to the successive reaction steps. An important intermediate, a tetramer of hydrogen cyanide was observed to be formed at room temperature. The amounts of this compound progressively increased with time. It was speculated that the purines which were identified in the refluxed sample were synthesized through the above tetramer. Compounds which are thought to be heterocyclic (max:250-265nm) were initially formed in the sample trapped at liquid nitrogen temperature. After hydrolysis with hydrochloric acid, Gly, Asp Ala, etc. were observed in the sample. Overall yield of organic compounds was estimates at 5-6% based on input carbon of methane."} {"id": "PMID:168541", "title": "Formation of prebiochemical compounds in models of the primitive earth's atmosphere. I: CH4 NH3 and CH4 N2 atmospheres.", "content": "In order to understand the formation of organic compounds in the primitive atmosphere, the first steps of evolution in models of the primitive atmosphere were investigated. Mixtures containing C-H-N elements were subjected to a low pressure silent electric discharge for several seconds, and the resulting effluents were analysed mainly by gas chromatography, infrared spectrometry and chemical analysis. The formation of hydrocarbon (i.e. ethylene, acetylene, methylacetylene) and of nitrogen containing compounds (i.e. hydrogen cyanide, cyanogen, saturated nitriles, acylonitrile, cyanoacetylene) is reported. The influence of the initial mixture composition on the amount of compounds formed was systematically studied. The nature of the nitrogen source (N2 or NH3) in the primitive atmosphere has a great influence on the amount and on the very nature of the synthesized products. It is shown that important precursors such as cyanogen and cyanoacetylene are formed only in very rich N2 mediums. These results show the important role played by the nature of the primitive atmosphere in the determination of the chemical evolution pathways.", "contents": "Formation of prebiochemical compounds in models of the primitive earth's atmosphere. I: CH4 NH3 and CH4 N2 atmospheres. In order to understand the formation of organic compounds in the primitive atmosphere, the first steps of evolution in models of the primitive atmosphere were investigated. Mixtures containing C-H-N elements were subjected to a low pressure silent electric discharge for several seconds, and the resulting effluents were analysed mainly by gas chromatography, infrared spectrometry and chemical analysis. The formation of hydrocarbon (i.e. ethylene, acetylene, methylacetylene) and of nitrogen containing compounds (i.e. hydrogen cyanide, cyanogen, saturated nitriles, acylonitrile, cyanoacetylene) is reported. The influence of the initial mixture composition on the amount of compounds formed was systematically studied. The nature of the nitrogen source (N2 or NH3) in the primitive atmosphere has a great influence on the amount and on the very nature of the synthesized products. It is shown that important precursors such as cyanogen and cyanoacetylene are formed only in very rich N2 mediums. These results show the important role played by the nature of the primitive atmosphere in the determination of the chemical evolution pathways."} {"id": "PMID:168551", "title": "The natural history of the Silver-Russell syndrome: a longitudinal study of thirty-nine cases.", "content": "The growth of 39 children with Silver-Russell syndrome has been followed for 1-13 years. Pregnancy and labor were normal; none of the 61 sibs had the syndrome. Height at referral (mean age 4.6 years) averaged 3.6 SD below the mean and remained at this level during subsequent growth. Bone age averaged 69 percent of normal at referral but caught up by puberty, which occurred at the normal time. Nineteen cases were treated with human growth hormone without lasting effect. There is no clear-cut distinction between the Silver and Russell syndromes; the name should be Silver-Russell. It is likely that some 10 percent of cases have birth weights in the minus 1.5 to minus 2.0 SD range.", "contents": "The natural history of the Silver-Russell syndrome: a longitudinal study of thirty-nine cases. The growth of 39 children with Silver-Russell syndrome has been followed for 1-13 years. Pregnancy and labor were normal; none of the 61 sibs had the syndrome. Height at referral (mean age 4.6 years) averaged 3.6 SD below the mean and remained at this level during subsequent growth. Bone age averaged 69 percent of normal at referral but caught up by puberty, which occurred at the normal time. Nineteen cases were treated with human growth hormone without lasting effect. There is no clear-cut distinction between the Silver and Russell syndromes; the name should be Silver-Russell. It is likely that some 10 percent of cases have birth weights in the minus 1.5 to minus 2.0 SD range."} {"id": "PMID:168552", "title": "The action of neurotransmitter hormones and analogues and cyclic nucleotides and theophylline on electrolyte transport by the excretory duct of the rabbit mandibular gland.", "content": "The effects of autonomic drugs on electrolyte transport by the main duct of the rabbit mandibular gland were studied in vitro. Acetylcholine, in concentrations as low as 10(-10) M, reduced nett Na+ reabsorption and partially depolarized the transepithelial potential difference (P.D.); the effects were blocked by atropine. Acetylcholine was relatively ineffective applied from the luminal rather than the interstitial surface of the duct. Noradrenaline and isoproterenol produced similar effects to acetylcholine but the minimum effective concentrations were much higher (10(-7) M and 10(-3) M, respectively). It was concluded that the duct cells possessed specific muscarinic receptors on the basal cell membrane but that adrenergic receptors, particularly beta receptors, were either scanty or lacking altogether. Theophylline (10(-5) M) could mimic the effects of the autonomic drugs and produced a dramatic potentiation of the action of acetylcholine. Both cAMP and cGMP (4 times 10(-5) M) mimicked the acetylcholine response but cAMP was only effective when applied to the luminal cell membrane. It is proposed that cAMP is the intracellular mediator of the acetylcholine response and that it produces some of its effects by acting on an enzyme system close to the apical cell membrane.", "contents": "The action of neurotransmitter hormones and analogues and cyclic nucleotides and theophylline on electrolyte transport by the excretory duct of the rabbit mandibular gland. The effects of autonomic drugs on electrolyte transport by the main duct of the rabbit mandibular gland were studied in vitro. Acetylcholine, in concentrations as low as 10(-10) M, reduced nett Na+ reabsorption and partially depolarized the transepithelial potential difference (P.D.); the effects were blocked by atropine. Acetylcholine was relatively ineffective applied from the luminal rather than the interstitial surface of the duct. Noradrenaline and isoproterenol produced similar effects to acetylcholine but the minimum effective concentrations were much higher (10(-7) M and 10(-3) M, respectively). It was concluded that the duct cells possessed specific muscarinic receptors on the basal cell membrane but that adrenergic receptors, particularly beta receptors, were either scanty or lacking altogether. Theophylline (10(-5) M) could mimic the effects of the autonomic drugs and produced a dramatic potentiation of the action of acetylcholine. Both cAMP and cGMP (4 times 10(-5) M) mimicked the acetylcholine response but cAMP was only effective when applied to the luminal cell membrane. It is proposed that cAMP is the intracellular mediator of the acetylcholine response and that it produces some of its effects by acting on an enzyme system close to the apical cell membrane."} {"id": "PMID:168554", "title": "[Biological examination in hyperlipemia].", "content": "The authors review the various methods of investigation useful in the classification of hyperlipoproteinaemias. Estimation of cholesterol and triglycerides remain the most important elements but do not suffice alone to reach a conclusion and measurement of phospholipids would seem to be a useful addition. Electrophoresis on agar, isolating a larger quantity of prebetalipoproteins, does not always facilitate classification. Finally, ultracentrifugation is often necessary in those forms which are difficult to classify, these representing almost 20 p.cent of patients.", "contents": "[Biological examination in hyperlipemia]. The authors review the various methods of investigation useful in the classification of hyperlipoproteinaemias. Estimation of cholesterol and triglycerides remain the most important elements but do not suffice alone to reach a conclusion and measurement of phospholipids would seem to be a useful addition. Electrophoresis on agar, isolating a larger quantity of prebetalipoproteins, does not always facilitate classification. Finally, ultracentrifugation is often necessary in those forms which are difficult to classify, these representing almost 20 p.cent of patients."} {"id": "PMID:168557", "title": "Catalytic oxidation of two ribonucleosides in the 5'-position.", "content": "Guanosine and 7-beta-D-ribofuranosyltheophylline was oxidized to the corresponding nucleoside 5'-carboxylic acids by molecular oxygen and a platinum catalyst.", "contents": "Catalytic oxidation of two ribonucleosides in the 5'-position. Guanosine and 7-beta-D-ribofuranosyltheophylline was oxidized to the corresponding nucleoside 5'-carboxylic acids by molecular oxygen and a platinum catalyst."} {"id": "PMID:168558", "title": "The 5' end group of tobacco mosaic virus RNA is m7G5' ppp5' Gp.", "content": "RNA extracted from CsC1-purified virions of tobacco mosaic virus is shown to give rise to an unusual nucleotide on digestion which RNAase T2, in addition to the four major nucleotides. This minor component has the electrophoretic characteristics of a phosphorylated end group, but is partially resistant to bacterial alkaline phosphatase. It is, however, a substrate for venom phosphodiesterase or nucleotide pyrophosphatase, yielding products which imply the structure m7G5'ppp5'Gp. TMV RNA, like many animal cellular and viral mRNAs recently examined, therefore has a 5' terminus blocked by a methylated nucleotide inverted with respect to the rest of the chain.", "contents": "The 5' end group of tobacco mosaic virus RNA is m7G5' ppp5' Gp. RNA extracted from CsC1-purified virions of tobacco mosaic virus is shown to give rise to an unusual nucleotide on digestion which RNAase T2, in addition to the four major nucleotides. This minor component has the electrophoretic characteristics of a phosphorylated end group, but is partially resistant to bacterial alkaline phosphatase. It is, however, a substrate for venom phosphodiesterase or nucleotide pyrophosphatase, yielding products which imply the structure m7G5'ppp5'Gp. TMV RNA, like many animal cellular and viral mRNAs recently examined, therefore has a 5' terminus blocked by a methylated nucleotide inverted with respect to the rest of the chain."} {"id": "PMID:168559", "title": "Non-random frequencies of short oligonucleotide sequences within poliomyelitis and encephalomyocarditis virus RNAs.", "content": "In poliomyelitis and encephalomyocarditis virus RNAs the relative frequencies of several short oligonucleotide sequences differ substantially from those expected on a random basis. The frequencies of CpGp-containing sequences are low, and the frequency of GpUpApGp is considerably lower than that of GpApUpGp. The relationship of these findings to those obtained from host cell RNAs is descussed.", "contents": "Non-random frequencies of short oligonucleotide sequences within poliomyelitis and encephalomyocarditis virus RNAs. In poliomyelitis and encephalomyocarditis virus RNAs the relative frequencies of several short oligonucleotide sequences differ substantially from those expected on a random basis. The frequencies of CpGp-containing sequences are low, and the frequency of GpUpApGp is considerably lower than that of GpApUpGp. The relationship of these findings to those obtained from host cell RNAs is descussed."} {"id": "PMID:168563", "title": "Effect of selected environmental treatments on the incidence of gross Marek's disease lesions in chickens.", "content": "The effects of selected environmental treatments on the incidence of gross Marek's disease (MD) lesions in chickens contact exposed to MD virus were examined. Treatments were high levels of airborne decomposition products from chicken litter in the rearing environment, disinfectants applied to chickens and their environments, and formaldehyde fumigation of eggs and newly hatched chicks. There were no significant differences in the incidence of gross MD lesions when treated and untreated groups were compared.", "contents": "Effect of selected environmental treatments on the incidence of gross Marek's disease lesions in chickens. The effects of selected environmental treatments on the incidence of gross Marek's disease (MD) lesions in chickens contact exposed to MD virus were examined. Treatments were high levels of airborne decomposition products from chicken litter in the rearing environment, disinfectants applied to chickens and their environments, and formaldehyde fumigation of eggs and newly hatched chicks. There were no significant differences in the incidence of gross MD lesions when treated and untreated groups were compared."} {"id": "PMID:168564", "title": "Serological responses of broiler-type chickens, with and without Newcastle disease and infectious Bronchitis vaccine, to experimental infection with Mycoplasma synoviae by foot pad, air sac and aerosol.", "content": "Serum plate (SP) and tube agglutination (TA) reactions and geometric mean Mycoplasma synoviae (Ms.) hemagglutination-inhibition (HI) titers were determined on chickens infected at 21 days of age with Ms. by foot pad, air sac and aerosol. One-half had been given Newcastle disease (ND) and infectious bronchitis (IB) vaccine in the water at 20 days of age, and the other half had not been vaccinated with ND and IB vaccine. Blood was taken at 3, 4, 6 and 8 weeks after Ms. infection. Geometric mean HI titers were determined on serums of chickens that had a foot pad injection of Ms. 8 weeks after Ms. infection and were bled at 1, 3 and 5 weeks after foot pad booster. Three weeks after aerosol exposure with Ms., the geometric mean HI titer was significantly higher in the ND- and IB-vaccinated birds than in the nonvaccinated birds. In the Ms. air sac-infected group of nonvaccinated birds the geometric mean HI titer had increased significantly 3 weeks after food pad challenge with Ms. In the Ms. air sac-infected group of vaccinated birds, the geometric mean HI titer had significantly increased 3 and 5 weeks after foot pad challenge with Ms.", "contents": "Serological responses of broiler-type chickens, with and without Newcastle disease and infectious Bronchitis vaccine, to experimental infection with Mycoplasma synoviae by foot pad, air sac and aerosol. Serum plate (SP) and tube agglutination (TA) reactions and geometric mean Mycoplasma synoviae (Ms.) hemagglutination-inhibition (HI) titers were determined on chickens infected at 21 days of age with Ms. by foot pad, air sac and aerosol. One-half had been given Newcastle disease (ND) and infectious bronchitis (IB) vaccine in the water at 20 days of age, and the other half had not been vaccinated with ND and IB vaccine. Blood was taken at 3, 4, 6 and 8 weeks after Ms. infection. Geometric mean HI titers were determined on serums of chickens that had a foot pad injection of Ms. 8 weeks after Ms. infection and were bled at 1, 3 and 5 weeks after foot pad booster. Three weeks after aerosol exposure with Ms., the geometric mean HI titer was significantly higher in the ND- and IB-vaccinated birds than in the nonvaccinated birds. In the Ms. air sac-infected group of nonvaccinated birds the geometric mean HI titer had increased significantly 3 weeks after food pad challenge with Ms. In the Ms. air sac-infected group of vaccinated birds, the geometric mean HI titer had significantly increased 3 and 5 weeks after foot pad challenge with Ms."} {"id": "PMID:168565", "title": "Activity of liver fructose diphosphatase from chick embryos treated with aminoguanidine sulfate.", "content": "Injection of chick embryos with aminoguanidine sulfate (AGS) on the fourth day of incubation resulted in a decreased specific activity of liver fructose diphosphatase (FDPase) prior to hatch time. This decreased FDPase specific activity was found to be the consequence of increased levels of an enzyme inhibitor (adenosin 5'-monophosphate) rather than a specific repression of enzyme synthesis.", "contents": "Activity of liver fructose diphosphatase from chick embryos treated with aminoguanidine sulfate. Injection of chick embryos with aminoguanidine sulfate (AGS) on the fourth day of incubation resulted in a decreased specific activity of liver fructose diphosphatase (FDPase) prior to hatch time. This decreased FDPase specific activity was found to be the consequence of increased levels of an enzyme inhibitor (adenosin 5'-monophosphate) rather than a specific repression of enzyme synthesis."} {"id": "PMID:168561", "title": "Metabolism of some ethylenediamine derivatives with antiarrhythmic properties. I. Absorption, distribution in tissues and excretion of 14-C labelled N, N'-bis-[3-(p-methoxyphenoxy)-2-hydroxypropyl]-ethylenediamine dimethanesulphonate (MK-142) in rats.", "content": "14-C labelled MK-142 (specific activity 2.875 muCi/mg) (1.762 mCi/mM) passes very rapidly from the blood stream to the majority of tissues since 5 min after the iv administration the blood contained only about 5% of the administered dose. The relatively high content of MK-142 in the myocardium as compared with its content in the skeletal muscles indicates a high affinity of the examined substance to the heart muscle. MK-142 is excreted via kidneys, alimentary tract and respiratory ways.", "contents": "Metabolism of some ethylenediamine derivatives with antiarrhythmic properties. I. Absorption, distribution in tissues and excretion of 14-C labelled N, N'-bis-[3-(p-methoxyphenoxy)-2-hydroxypropyl]-ethylenediamine dimethanesulphonate (MK-142) in rats. 14-C labelled MK-142 (specific activity 2.875 muCi/mg) (1.762 mCi/mM) passes very rapidly from the blood stream to the majority of tissues since 5 min after the iv administration the blood contained only about 5% of the administered dose. The relatively high content of MK-142 in the myocardium as compared with its content in the skeletal muscles indicates a high affinity of the examined substance to the heart muscle. MK-142 is excreted via kidneys, alimentary tract and respiratory ways."} {"id": "PMID:168566", "title": "Molecular sizes of egg yolk very low density lipoproteins fractionated by ultracentrifugation.", "content": "Egg yolk very low density lipoproteins isolated from normal eggs were separated into six fractions by preparative ultracentrifugation. The sizes of the molecules in three of the fractions were estimated by gel chromatography and by electron microscopy of the lipoproteins using a negative staining technique. The three fractions had average diameters of 39 nm., 32 n., and 25 nm. and average molecular weights of 17 X 10(6), 10 X 10(6), and 5 X 10(6). There was considerable overlap of size of molecules in the three fractions. Size differences were not observed in the ultracentrifuge separated fractions of very low density lipoproteins isolated from eggs laid by hens receiving crude cottonseed oil in their diets. However, the fatty acids from these fractions differed in stearic and oleic acid contents while those from the normal egg lipoproteins did not. The floating very low density lipoproteins contained more oleic acid and less stearic acid then the sedimenting ones did.", "contents": "Molecular sizes of egg yolk very low density lipoproteins fractionated by ultracentrifugation. Egg yolk very low density lipoproteins isolated from normal eggs were separated into six fractions by preparative ultracentrifugation. The sizes of the molecules in three of the fractions were estimated by gel chromatography and by electron microscopy of the lipoproteins using a negative staining technique. The three fractions had average diameters of 39 nm., 32 n., and 25 nm. and average molecular weights of 17 X 10(6), 10 X 10(6), and 5 X 10(6). There was considerable overlap of size of molecules in the three fractions. Size differences were not observed in the ultracentrifuge separated fractions of very low density lipoproteins isolated from eggs laid by hens receiving crude cottonseed oil in their diets. However, the fatty acids from these fractions differed in stearic and oleic acid contents while those from the normal egg lipoproteins did not. The floating very low density lipoproteins contained more oleic acid and less stearic acid then the sedimenting ones did."} {"id": "PMID:168562", "title": "Pharmacological studies on 2- and 4-pyridylethylamides of acetyltropic acid (PAT-2 and PAT-4).", "content": "Two new compounds: 2- and 4-pyridylmethylamides of acetyltropic acid (PAT 2 and PAT-4) show spasmolytic effects on isolated guinea pig ileum, have mydriatic actevity in rabbits and block restraint produced ulceration in rats. PAT-4 causes a strong inhibition of the salivary secretion in mice. Both of the test compounds inhibit also the effects of ACh and vagus stimulation on the blood pressure and have local anaesthetic activity. PAT-4 inhibits the aggressive behaviour in mice and rats, prolongs the hexobarbital sleeping time, increases the pain treshold and inhibits the oxotremorine induced tremor in mice. Both PAT-2 and PAT-4 had no effect on the convulsant action of pentetrazole. EEG findings show that central cholinolytic activity is present in both compound tested.", "contents": "Pharmacological studies on 2- and 4-pyridylethylamides of acetyltropic acid (PAT-2 and PAT-4). Two new compounds: 2- and 4-pyridylmethylamides of acetyltropic acid (PAT 2 and PAT-4) show spasmolytic effects on isolated guinea pig ileum, have mydriatic actevity in rabbits and block restraint produced ulceration in rats. PAT-4 causes a strong inhibition of the salivary secretion in mice. Both of the test compounds inhibit also the effects of ACh and vagus stimulation on the blood pressure and have local anaesthetic activity. PAT-4 inhibits the aggressive behaviour in mice and rats, prolongs the hexobarbital sleeping time, increases the pain treshold and inhibits the oxotremorine induced tremor in mice. Both PAT-2 and PAT-4 had no effect on the convulsant action of pentetrazole. EEG findings show that central cholinolytic activity is present in both compound tested."} {"id": "PMID:168567", "title": "Reduction of aflatoxin effects of quail.", "content": "A natural occuring outbreak of aflatoxicosis was observed in Bobwhite quail chicks while on a brooding experiment. A slight reduction in effects was noted for birds which received Tylan in the water from 0-3 days and Terramycin from 0-35 days of age. No symptoms of aflatoxicosis were observed in birds which received a product (FloxAid) containing two antibiotics and eight vitamins from 0-14 days. It is postulated that the primary mode of protection was via the water soluble vitamin D content of the product with possibly some protection from vitamins A, E and K.", "contents": "Reduction of aflatoxin effects of quail. A natural occuring outbreak of aflatoxicosis was observed in Bobwhite quail chicks while on a brooding experiment. A slight reduction in effects was noted for birds which received Tylan in the water from 0-3 days and Terramycin from 0-35 days of age. No symptoms of aflatoxicosis were observed in birds which received a product (FloxAid) containing two antibiotics and eight vitamins from 0-14 days. It is postulated that the primary mode of protection was via the water soluble vitamin D content of the product with possibly some protection from vitamins A, E and K."} {"id": "PMID:168569", "title": "Isolation and characterization of collagen-synthesizing polysomes from chick embryos.", "content": "Collagen-synthesizing polysomes were isolated by low-speed centrifugation of the post-mitochondrial supernatant of chick homogenates. Electron microscopy of the fraction thus isolated shows it to be exclusively composed of ribosomes. Amino acid incorporation in vitro showed that these particles were efficient in the incorporation of proline, but not tryptophan, as opposed to ribosomes obtained from the supernatant of the low-speed centrifugation. The incorporation process was highly dependent on GTP, and exibited an optimal Mg2+concentration of 5.6mM. The reaction was inhibited by RNase, elongation inhibitors as anysomycin, sparsomycin, fusidic acid and GDPCP. It was also moderately inhibited by initiation inhibitors such as aurintricarboxilic acid and pyrocatechol violet. The product of the incorporation was characterized as collagen by its sensitivity towards purified collagenase, lack of tryptophan, chromatography in CM-cellulose and molecular sieve chromatography in Sephadex G-200.", "contents": "Isolation and characterization of collagen-synthesizing polysomes from chick embryos. Collagen-synthesizing polysomes were isolated by low-speed centrifugation of the post-mitochondrial supernatant of chick homogenates. Electron microscopy of the fraction thus isolated shows it to be exclusively composed of ribosomes. Amino acid incorporation in vitro showed that these particles were efficient in the incorporation of proline, but not tryptophan, as opposed to ribosomes obtained from the supernatant of the low-speed centrifugation. The incorporation process was highly dependent on GTP, and exibited an optimal Mg2+concentration of 5.6mM. The reaction was inhibited by RNase, elongation inhibitors as anysomycin, sparsomycin, fusidic acid and GDPCP. It was also moderately inhibited by initiation inhibitors such as aurintricarboxilic acid and pyrocatechol violet. The product of the incorporation was characterized as collagen by its sensitivity towards purified collagenase, lack of tryptophan, chromatography in CM-cellulose and molecular sieve chromatography in Sephadex G-200."} {"id": "PMID:168570", "title": "Regulation of sensitivity to beta-adrenergic stimulation in induction of pineal N-acetyltransferase.", "content": "Stimulation by isoproterenol causes large increases in the activity of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) after a variable lag period. Lengthening periods of exposure to light cause rapid increases in the sensitivity of pineal N-acetyltransferase to induction by isoproterenol. This supersensitivity, which develops gradually over a 12 hr period, is correlated with increasingly longer lag periods in the induction of the enzyme, and with progressively greater maximal response. Repeated administration of isoproterenol to supersensitive animals rapidly reverses the above changes and causes relative subsensitivity. The sensitivity of N-acetyltransferase to induction by dibutyryl-cyclic tamp added to pineals in organ culture was found to change in parallel with the sensitivity to isoproterenol. Stimulation of cyclic AMP levels in the pineal by isoproterenol was also greater in supersensitive rats than in the subsensitive animals, whether the supersensitivity had been caused by denervation or by exposure to light for 12 hr. The above experiments suggest that there are two sites for the regulation of the sensitivity of N-acetyltransferase to induction by catecholamines. The first site regulates the capacity of intracellular processes (i.e., induction of tn-acetyltransferase) to respond to cyclic AMP as a second messenger.", "contents": "Regulation of sensitivity to beta-adrenergic stimulation in induction of pineal N-acetyltransferase. Stimulation by isoproterenol causes large increases in the activity of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) after a variable lag period. Lengthening periods of exposure to light cause rapid increases in the sensitivity of pineal N-acetyltransferase to induction by isoproterenol. This supersensitivity, which develops gradually over a 12 hr period, is correlated with increasingly longer lag periods in the induction of the enzyme, and with progressively greater maximal response. Repeated administration of isoproterenol to supersensitive animals rapidly reverses the above changes and causes relative subsensitivity. The sensitivity of N-acetyltransferase to induction by dibutyryl-cyclic tamp added to pineals in organ culture was found to change in parallel with the sensitivity to isoproterenol. Stimulation of cyclic AMP levels in the pineal by isoproterenol was also greater in supersensitive rats than in the subsensitive animals, whether the supersensitivity had been caused by denervation or by exposure to light for 12 hr. The above experiments suggest that there are two sites for the regulation of the sensitivity of N-acetyltransferase to induction by catecholamines. The first site regulates the capacity of intracellular processes (i.e., induction of tn-acetyltransferase) to respond to cyclic AMP as a second messenger."} {"id": "PMID:168571", "title": "Reversible dissociation of a carbamoyl phosphate synthase-aspartate transcarbamoylase-dihydroorotase complex from ovarian eggs of Rana catesbeiana: effect of uridine triphosphate and other modifiers.", "content": "Glutamine-dependent carbanoyl phosphate synthase [ATP6carbamate phosphotransgerase (dephosphorylating), EC 2.7.2.9], aspartate transcarbamoylase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3), are copurified as a high-molicular-weight complex from extracts of unfertilized eggs of Rana catesbeiana. UTP is required to maintain the integrity of the complex during the last two purification steps. Removal of the nucleotide results in dissociation of the complex. Based on sedimentation behavior in glycerol gradients, the dissociated carbamoyl phosphate synthase has an apparent molecular weight of 260,000 +/- 20,000 and that of dihydroorotase is estimated at 280,000 +/- 20,000. Aspartate transcarbamoylase is broadly distributed over the gradient. The addition of ATP, 5-phosphoribosyl-1-pyrophosphate, Mg++, or inorganic phosphate to the dossociated complex results in the appearance of a peak of aspartate transcarbamoylase activity with an apparent molecular weight of 110,000 +/- 10,000. Icubation of a mixture of the dissociated enzymes with UTP and Mg++ leads to their reassociation into the high-molecular-weight complex.", "contents": "Reversible dissociation of a carbamoyl phosphate synthase-aspartate transcarbamoylase-dihydroorotase complex from ovarian eggs of Rana catesbeiana: effect of uridine triphosphate and other modifiers. Glutamine-dependent carbanoyl phosphate synthase [ATP6carbamate phosphotransgerase (dephosphorylating), EC 2.7.2.9], aspartate transcarbamoylase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3), are copurified as a high-molicular-weight complex from extracts of unfertilized eggs of Rana catesbeiana. UTP is required to maintain the integrity of the complex during the last two purification steps. Removal of the nucleotide results in dissociation of the complex. Based on sedimentation behavior in glycerol gradients, the dissociated carbamoyl phosphate synthase has an apparent molecular weight of 260,000 +/- 20,000 and that of dihydroorotase is estimated at 280,000 +/- 20,000. Aspartate transcarbamoylase is broadly distributed over the gradient. The addition of ATP, 5-phosphoribosyl-1-pyrophosphate, Mg++, or inorganic phosphate to the dossociated complex results in the appearance of a peak of aspartate transcarbamoylase activity with an apparent molecular weight of 110,000 +/- 10,000. Icubation of a mixture of the dissociated enzymes with UTP and Mg++ leads to their reassociation into the high-molecular-weight complex."} {"id": "PMID:168572", "title": "Motion of subfragment-1 in myosin and its supramolecular complexes: saturation transfer electron paramagnetic resonance.", "content": "Molecular dynamics in spin-labeled muscle proteins was studied with a recently developed electron paramagnetic resonance (EPR) technique, saturation transfer spectroscopy, which is uniquely sensitive to rotational motion in the range of 10(-7)-10(-3) sec. Rotational correlation time (tau2) were determined for a spin label analog of iodoacetamide bound to the subfragment-1 (S-1) region of myosin under a variety of conditions likely to shed light on the molecular mechanism of muscle contraction. Results show that (a) the spin labels are rigidly bound to the isolated S-1 (tau2 = 2 x 10(-7) sec) and can be used to estimate values of tau2 for the S-1 region of the myosin molecule; (b) in solutions of intact myosin, S-1 has considerable mobility relative to the rest of the myosin molecule, the value of tau2 for the S-1 segment of myosin being less than twice that for isolated S-1, while the molecular weights differ by a factor of 4 to 5; (c) in myosin filaments, tau2 increases by a factor of only about 10, suggesting motion of the S-1 regions independent of the backbone of the myosin filament, but slower than that in a single molecule; (d) addition of F-actin to solutions of myosin or S-1 increases tau2 by a factor of nearly 10(3), indicating strong immobilization of S-1 upon binding to actin. Saturation transfer spectroscopy promises to provide an extremely useful tool for the study of the motions of the crossbridges and thin filaments in reconstituted systems and in glycerinated muscle fibers.", "contents": "Motion of subfragment-1 in myosin and its supramolecular complexes: saturation transfer electron paramagnetic resonance. Molecular dynamics in spin-labeled muscle proteins was studied with a recently developed electron paramagnetic resonance (EPR) technique, saturation transfer spectroscopy, which is uniquely sensitive to rotational motion in the range of 10(-7)-10(-3) sec. Rotational correlation time (tau2) were determined for a spin label analog of iodoacetamide bound to the subfragment-1 (S-1) region of myosin under a variety of conditions likely to shed light on the molecular mechanism of muscle contraction. Results show that (a) the spin labels are rigidly bound to the isolated S-1 (tau2 = 2 x 10(-7) sec) and can be used to estimate values of tau2 for the S-1 region of the myosin molecule; (b) in solutions of intact myosin, S-1 has considerable mobility relative to the rest of the myosin molecule, the value of tau2 for the S-1 segment of myosin being less than twice that for isolated S-1, while the molecular weights differ by a factor of 4 to 5; (c) in myosin filaments, tau2 increases by a factor of only about 10, suggesting motion of the S-1 regions independent of the backbone of the myosin filament, but slower than that in a single molecule; (d) addition of F-actin to solutions of myosin or S-1 increases tau2 by a factor of nearly 10(3), indicating strong immobilization of S-1 upon binding to actin. Saturation transfer spectroscopy promises to provide an extremely useful tool for the study of the motions of the crossbridges and thin filaments in reconstituted systems and in glycerinated muscle fibers."} {"id": "PMID:168573", "title": "Inhibition by interferon of delayed-type hypersensitivity in the mouse.", "content": "The effect of interferon on delayed-type by persensitivity to picryl chloride and sheep erythrocytes was examined in the mouse. When administered to sensitized animals on the day before or the day of challenge, tissue culture interferon inhibited both the ear swelling induced by pieryl chloride and footpad swelling induced by sheep erythrocytes. Newcastle disease virus, when injected into sensitized If-1l or If-1h congenic mice a few hours before challenge, caused an inhibition of delayed-type hypersensitivity which could be related to the amount of serum interferon induced by the virus. These results indicate that interferon production may represent one of the factors responsible for the depression of cell-mediated immune reactions during virus infection.", "contents": "Inhibition by interferon of delayed-type hypersensitivity in the mouse. The effect of interferon on delayed-type by persensitivity to picryl chloride and sheep erythrocytes was examined in the mouse. When administered to sensitized animals on the day before or the day of challenge, tissue culture interferon inhibited both the ear swelling induced by pieryl chloride and footpad swelling induced by sheep erythrocytes. Newcastle disease virus, when injected into sensitized If-1l or If-1h congenic mice a few hours before challenge, caused an inhibition of delayed-type hypersensitivity which could be related to the amount of serum interferon induced by the virus. These results indicate that interferon production may represent one of the factors responsible for the depression of cell-mediated immune reactions during virus infection."} {"id": "PMID:168574", "title": "Anatomy of herpes simplex virus DNA: strain differences and heterogeneity in the locations of restriction endonuclease cleavage sites.", "content": "Digestion of herpes simplex virus DNA by the HinIII or Eco RI restriction endonucleases yielded 11 to 15 fragments with molecular weights between 1 x 10(6) and 28 x10(6). The electrophoretic profiles obtained in 0.3% agarose gels with DNA fragments from none different strains of herpes simplex virus type 1 could be readily differentiated from the patterns exhibited by the corresponding fragments from four separate strains of type 2 virus; however, with each serotype, the laboratory strains differed significantly among themselves and also from isolates passaged a minimum number of times outside the human host. Digestion of all DNAs of herpes simples virus with either enzyme reproducibly generated two classes of fragments (major and minor) which differed in molar ocncentration. Moreover, although the molecular weight of an intact herpes simplex 1(F1) DNA molecule is approximately 98 x 10(6), the summed molecular weights of all major and minor HinIII fragments totalled 160 x 10(6), and the seven major fragments alone accounted for only 60 x 10(6). These unusual features indicate the existence of limited heterogeneity in the positions of cleavage sitet along individual molecules. We have eliminated the possibility that minor fragments arose from contamination with the defective DNA of high byoyant density which appears on serial undiluted passage of the virus. In fact, this latter type of DNA was resistant to cleavage by HinIII and gave large amounts of only two species of EcoRI fragments; suggesting that the defective molecules consist of many tandem repeats of a small segment of viral DNA. The heterogeneity in the viral DNA of normal density appears to be related to the structural organization of the molecules and does not necessarily imply differences in genetic content.", "contents": "Anatomy of herpes simplex virus DNA: strain differences and heterogeneity in the locations of restriction endonuclease cleavage sites. Digestion of herpes simplex virus DNA by the HinIII or Eco RI restriction endonucleases yielded 11 to 15 fragments with molecular weights between 1 x 10(6) and 28 x10(6). The electrophoretic profiles obtained in 0.3% agarose gels with DNA fragments from none different strains of herpes simplex virus type 1 could be readily differentiated from the patterns exhibited by the corresponding fragments from four separate strains of type 2 virus; however, with each serotype, the laboratory strains differed significantly among themselves and also from isolates passaged a minimum number of times outside the human host. Digestion of all DNAs of herpes simples virus with either enzyme reproducibly generated two classes of fragments (major and minor) which differed in molar ocncentration. Moreover, although the molecular weight of an intact herpes simplex 1(F1) DNA molecule is approximately 98 x 10(6), the summed molecular weights of all major and minor HinIII fragments totalled 160 x 10(6), and the seven major fragments alone accounted for only 60 x 10(6). These unusual features indicate the existence of limited heterogeneity in the positions of cleavage sitet along individual molecules. We have eliminated the possibility that minor fragments arose from contamination with the defective DNA of high byoyant density which appears on serial undiluted passage of the virus. In fact, this latter type of DNA was resistant to cleavage by HinIII and gave large amounts of only two species of EcoRI fragments; suggesting that the defective molecules consist of many tandem repeats of a small segment of viral DNA. The heterogeneity in the viral DNA of normal density appears to be related to the structural organization of the molecules and does not necessarily imply differences in genetic content."} {"id": "PMID:168575", "title": "Action of feedback regulator on adenylate cyclase.", "content": "A factor [the feedback regulator (FR)] formed by adipocytes after the stimulation of a cAMP raising hormone has been found to be a potent inhibitor of membrane-bound adenylate cyclase [EC 4.6.1.1.; ATP pyrophosphate-lyase (cyclizing)]. In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate cyclase by lowering the Vmax without affecting the apparent Km for ATP (0.3-0.6 mM). The apparent Ka for epinephrine (5-6 muM) was also not affected by FR. The inhibitory action of FR was partially countered by Mg2+ ions. An increase in phosphorylation of plasma membrane was observed when FR was present in the incubation system. The concentration required for a 50% inhibition was four times higher when adenosine 5-(beta,gamma-imino) triphosphate [AMP-P(NH)P] replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused by FR. Increase in FR inhibition obtained by adding low concentrations of adenosine 5-(alpha,beta-methylene) triphosphate or ATP to AMP-(NH)P as the substrate supports this view. The inhibitory action was reversible. These results are consistent with the previously reported phenomena that (1) the undue to the formation of FR, and (2) the recovery of responsiveness of the stimulated cells by washing the cells with regular buffer medium is a result of the removal of FR. The hormone-initiated biphasic curve of cAMP levels in adipocytes is believed to be due to the negative feedback action of FR on adenylate cyclase. The mechanism of action of FR on inhibition of adenylate cyclase appears to be related to the phosphorylation of certain membrane components.", "contents": "Action of feedback regulator on adenylate cyclase. A factor [the feedback regulator (FR)] formed by adipocytes after the stimulation of a cAMP raising hormone has been found to be a potent inhibitor of membrane-bound adenylate cyclase [EC 4.6.1.1.; ATP pyrophosphate-lyase (cyclizing)]. In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate cyclase by lowering the Vmax without affecting the apparent Km for ATP (0.3-0.6 mM). The apparent Ka for epinephrine (5-6 muM) was also not affected by FR. The inhibitory action of FR was partially countered by Mg2+ ions. An increase in phosphorylation of plasma membrane was observed when FR was present in the incubation system. The concentration required for a 50% inhibition was four times higher when adenosine 5-(beta,gamma-imino) triphosphate [AMP-P(NH)P] replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused by FR. Increase in FR inhibition obtained by adding low concentrations of adenosine 5-(alpha,beta-methylene) triphosphate or ATP to AMP-(NH)P as the substrate supports this view. The inhibitory action was reversible. These results are consistent with the previously reported phenomena that (1) the undue to the formation of FR, and (2) the recovery of responsiveness of the stimulated cells by washing the cells with regular buffer medium is a result of the removal of FR. The hormone-initiated biphasic curve of cAMP levels in adipocytes is believed to be due to the negative feedback action of FR on adenylate cyclase. The mechanism of action of FR on inhibition of adenylate cyclase appears to be related to the phosphorylation of certain membrane components."} {"id": "PMID:168576", "title": "Nuclear receptors for thyroid hormone: evidence for nonrandom distribution within chromatin.", "content": "Chromatin receptor proteins appear to mediate some actions of thyroid hormone. In this study, sheared mammalian chromatin containing [125I]triiodothyronine (T3) bound by these receptors was separated using sucrose gradient velocity sedimentation. T3-receptor complexes were distributed throughout the chromatin fractions, but were enriched in the slowly sedimenting fractions. The latter contain most of the template capacity for RNA synthesis and most of the endogenous RNA polymerase activity but a minor portion of the total DNA. Formaldehyde treatment of chromatin containing receptor-bound [125 I ]T3 resulted in fixation of radioactivity, as evidenced by its migration with chromatin after equilibrium density gradient sedimentation in both cesium chloride and Conray. This fixation implies that the T3 receptor protein is closely associated with chromatin. These results suggest that proteins involved in the regulation of gene function may be nonrandomly distributed within chromatin subfractions, and are consistent with a direct role for thyroid hormone in regulating genetic expression.", "contents": "Nuclear receptors for thyroid hormone: evidence for nonrandom distribution within chromatin. Chromatin receptor proteins appear to mediate some actions of thyroid hormone. In this study, sheared mammalian chromatin containing [125I]triiodothyronine (T3) bound by these receptors was separated using sucrose gradient velocity sedimentation. T3-receptor complexes were distributed throughout the chromatin fractions, but were enriched in the slowly sedimenting fractions. The latter contain most of the template capacity for RNA synthesis and most of the endogenous RNA polymerase activity but a minor portion of the total DNA. Formaldehyde treatment of chromatin containing receptor-bound [125 I ]T3 resulted in fixation of radioactivity, as evidenced by its migration with chromatin after equilibrium density gradient sedimentation in both cesium chloride and Conray. This fixation implies that the T3 receptor protein is closely associated with chromatin. These results suggest that proteins involved in the regulation of gene function may be nonrandomly distributed within chromatin subfractions, and are consistent with a direct role for thyroid hormone in regulating genetic expression."} {"id": "PMID:168577", "title": "Structural changes inducted by follicle-stimulating hormone or dibutyryl cyclic AMP on presumptive Sertoli cells in culture.", "content": "Cells isolated from testes of 20-day-old rats, maintained in primary culture in a defined medium, are shown to respond to follicle-stimulating hormone or 3:5-cyclic AMP with characteristic morphological changes. No response is observed in cells treated with luteinizing hormone or 5-?AMP. The cells form a mono-layer, and have been identified as presumptive Sertoli cells structurally by identification of unique tight junctions in electron micrographs of the preparations, along with other ultrastructural properties characteristic of Sertoli cells in situ. These cells do not undergo mitosis. The presumptive Sertoli cells are shown to be morphologically and functionally different from peritubular fibroblasts grown in parallel cultures. Fibroblasts have high rates of mitosis, do not respond to follicle-stimulating hormone, and frequently form multilayers. Other information on the biochemical responses of the cells is cited, which supports the conclusion that the cultured cell preparations consist primarily of Sertoli cells.", "contents": "Structural changes inducted by follicle-stimulating hormone or dibutyryl cyclic AMP on presumptive Sertoli cells in culture. Cells isolated from testes of 20-day-old rats, maintained in primary culture in a defined medium, are shown to respond to follicle-stimulating hormone or 3:5-cyclic AMP with characteristic morphological changes. No response is observed in cells treated with luteinizing hormone or 5-?AMP. The cells form a mono-layer, and have been identified as presumptive Sertoli cells structurally by identification of unique tight junctions in electron micrographs of the preparations, along with other ultrastructural properties characteristic of Sertoli cells in situ. These cells do not undergo mitosis. The presumptive Sertoli cells are shown to be morphologically and functionally different from peritubular fibroblasts grown in parallel cultures. Fibroblasts have high rates of mitosis, do not respond to follicle-stimulating hormone, and frequently form multilayers. Other information on the biochemical responses of the cells is cited, which supports the conclusion that the cultured cell preparations consist primarily of Sertoli cells."} {"id": "PMID:168578", "title": "Folding of the DNA double helix in chromatin-like structures from simian virus 40.", "content": "Relaxed circular, covalently closed simian virus 40 DNA molecules were associated with the four histones that are present in virions. In electron micrographs the resulting complexes appear twisted, with globular structures (nucleosomes) along the DNA. Incubation with an untwisting extract converts the twisted complexes to relaxed structures. Extraction of the DNA from the relaxed complexes yields supercoiled molecules. The number of superhelical turns in these molecules corresponds to the number of nucleosomes per DNA molecule in the complexes.", "contents": "Folding of the DNA double helix in chromatin-like structures from simian virus 40. Relaxed circular, covalently closed simian virus 40 DNA molecules were associated with the four histones that are present in virions. In electron micrographs the resulting complexes appear twisted, with globular structures (nucleosomes) along the DNA. Incubation with an untwisting extract converts the twisted complexes to relaxed structures. Extraction of the DNA from the relaxed complexes yields supercoiled molecules. The number of superhelical turns in these molecules corresponds to the number of nucleosomes per DNA molecule in the complexes."} {"id": "PMID:168579", "title": "Interrelationship between poly (ADP-Rib) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb.", "content": "Mesodermal cells of embryonic chick limbs have the capacity to differentiate into either muscle or cartilage. Previous reports from this laboratory show a correlation between pyridine nucleotide levels and this differentiation, and thus suggest that fluctuations in the cellular NAD levels play a role in the control of muscle versus cartilage development. Poly(ADP-Rib) is chromatin-associated and forms from the polymerization of NAD with the excision of nicotinamide. The studies reported here show that: (A) the rate of net synthesis of poly(ADP-Rib) is correlated with the differentiation of chondrogenic cells from stage 24 limb mesodermal cells grown in vitro; (B) inhibition of chondrogenic expression caused by exposure to nicotinamide or BrdUrd is correlated with maintenance of basal levels of poly(ADP-Rib) synthesis, and this inhibition is dependent on the concentration of nicotinamide or BrdUrd exogenously supplied; (C) potentiation of chondrogenic expression caused by exposure of limb mesodermal cells in vitro to 3-acetylpyridine is correlated with stimulation of the rate of poly(ADP-Rib) synthesis if corrected for the specific activity of the ATP pool or compared to untreated cultures on a per cell basis; (D) isolated chromatin from mesodermal cells has the enzymatic machinery for synthesizing poly(ADP-Rib); (E) this machinery is inhibited by nicotinamide, thymidine, and 3-acetylpyridine; and (F) newly synthesized poly(ADP-Rib) is either associated with a discrete fraction of chromatin or is completely extracted from chromatin by the high column salts, which result in an aggregation with eventual elution at the exclusion volume position of the agarose column. Taken together, these observations provide a possible explanation for how fluctuations in cellular NAD levels can communicate with or be \"sensed\" by genomic related machinery and eventually result in differtial phenotypic expression.", "contents": "Interrelationship between poly (ADP-Rib) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb. Mesodermal cells of embryonic chick limbs have the capacity to differentiate into either muscle or cartilage. Previous reports from this laboratory show a correlation between pyridine nucleotide levels and this differentiation, and thus suggest that fluctuations in the cellular NAD levels play a role in the control of muscle versus cartilage development. Poly(ADP-Rib) is chromatin-associated and forms from the polymerization of NAD with the excision of nicotinamide. The studies reported here show that: (A) the rate of net synthesis of poly(ADP-Rib) is correlated with the differentiation of chondrogenic cells from stage 24 limb mesodermal cells grown in vitro; (B) inhibition of chondrogenic expression caused by exposure to nicotinamide or BrdUrd is correlated with maintenance of basal levels of poly(ADP-Rib) synthesis, and this inhibition is dependent on the concentration of nicotinamide or BrdUrd exogenously supplied; (C) potentiation of chondrogenic expression caused by exposure of limb mesodermal cells in vitro to 3-acetylpyridine is correlated with stimulation of the rate of poly(ADP-Rib) synthesis if corrected for the specific activity of the ATP pool or compared to untreated cultures on a per cell basis; (D) isolated chromatin from mesodermal cells has the enzymatic machinery for synthesizing poly(ADP-Rib); (E) this machinery is inhibited by nicotinamide, thymidine, and 3-acetylpyridine; and (F) newly synthesized poly(ADP-Rib) is either associated with a discrete fraction of chromatin or is completely extracted from chromatin by the high column salts, which result in an aggregation with eventual elution at the exclusion volume position of the agarose column. Taken together, these observations provide a possible explanation for how fluctuations in cellular NAD levels can communicate with or be \"sensed\" by genomic related machinery and eventually result in differtial phenotypic expression."} {"id": "PMID:168580", "title": "Somatic hybrid of thymus leukemia (.", "content": "A somatic hybrid of ASL-1 leukemia cells [H-2a, thymus leukemia (TL)1,2,3, Thy-1b] and LM(TK)-cells [H-2-k, TL(-), Thy-1 (-), thymidine kinase deficient] was formed with the aid of inactivated Sendai virus. The selection of hybrid cell clones was facilitated by the inability of ASL-1 cells to grow in vitro and of LM(TK)-cells to survive in hypoxanthine/amethopterin/thymidine medium. The H-2 antigens of both parental cells were formed in approximately equivalent amounts by the hybrid cells, and they possessed a hybrid karyotype. As determined by five independent experimental procedures (antibody and complement-mediated cytotoxicity tests, the reduction of specific antibody activity of antiserum of known titer, immunofluorescent tests, mixed hemagglutination tests, and their direct isolation), TL antigens but not Thy-1 antigens were formed by the hybrid cells. TL antigens of the hybrids failed to undergo modulation under conditions leading to the modulation of TL antigens of parental ASL-1 cells. Modulation was attempted with TL 1,3, TL 2, or TL 1,2,3 antisera of high titer. thybrid cells were incubated for up to 30 hr in medium with TL antisera. Both direct and indirect immune methods were attempted. These results indicate that cellular mechanisms controlling the expression of TL antigens may be distinguished from the capacity of the cells to undergo modulation.", "contents": "Somatic hybrid of thymus leukemia (. A somatic hybrid of ASL-1 leukemia cells [H-2a, thymus leukemia (TL)1,2,3, Thy-1b] and LM(TK)-cells [H-2-k, TL(-), Thy-1 (-), thymidine kinase deficient] was formed with the aid of inactivated Sendai virus. The selection of hybrid cell clones was facilitated by the inability of ASL-1 cells to grow in vitro and of LM(TK)-cells to survive in hypoxanthine/amethopterin/thymidine medium. The H-2 antigens of both parental cells were formed in approximately equivalent amounts by the hybrid cells, and they possessed a hybrid karyotype. As determined by five independent experimental procedures (antibody and complement-mediated cytotoxicity tests, the reduction of specific antibody activity of antiserum of known titer, immunofluorescent tests, mixed hemagglutination tests, and their direct isolation), TL antigens but not Thy-1 antigens were formed by the hybrid cells. TL antigens of the hybrids failed to undergo modulation under conditions leading to the modulation of TL antigens of parental ASL-1 cells. Modulation was attempted with TL 1,3, TL 2, or TL 1,2,3 antisera of high titer. thybrid cells were incubated for up to 30 hr in medium with TL antisera. Both direct and indirect immune methods were attempted. These results indicate that cellular mechanisms controlling the expression of TL antigens may be distinguished from the capacity of the cells to undergo modulation."} {"id": "PMID:168581", "title": "Genetic control of endogenous C-type virus production in pancreatic acinar cells of C57BL/He and C57BL/6J mice.", "content": "Electron microscopy revealed very active production of C-type virus particles in the pancreatic acinar cells of untreated normal adult mice of the C57BL/He strain. In C57BL/6J mice, a similar picture was observed after a single intraperitoneal injection of dexamethasone. No viruses were observed in the pancreas of untreated or dexamethasone-treated BALB/c and C3Hf mice. F1 hybrids of both C57BL strains with C3Hf mice produced viruses in the same manner and quantity as the C57BL parents, whereas hybrids with BALB/c mice were entirely negative. Approximately 50% of mice of the first backcross generation of (BALB/c times C57BL/He)F1 hybrids with C57BL/He mice were active producers of C-type particles, while the other 50% were negative. It is suggested that a regulator gene that controls C-type virus production does not function in the pancreatic cells of either C57BL strain, and that BALB/c mice can provide hybrids with an active regulator.", "contents": "Genetic control of endogenous C-type virus production in pancreatic acinar cells of C57BL/He and C57BL/6J mice. Electron microscopy revealed very active production of C-type virus particles in the pancreatic acinar cells of untreated normal adult mice of the C57BL/He strain. In C57BL/6J mice, a similar picture was observed after a single intraperitoneal injection of dexamethasone. No viruses were observed in the pancreas of untreated or dexamethasone-treated BALB/c and C3Hf mice. F1 hybrids of both C57BL strains with C3Hf mice produced viruses in the same manner and quantity as the C57BL parents, whereas hybrids with BALB/c mice were entirely negative. Approximately 50% of mice of the first backcross generation of (BALB/c times C57BL/He)F1 hybrids with C57BL/He mice were active producers of C-type particles, while the other 50% were negative. It is suggested that a regulator gene that controls C-type virus production does not function in the pancreatic cells of either C57BL strain, and that BALB/c mice can provide hybrids with an active regulator."} {"id": "PMID:168582", "title": "Simian virus 40 DNA directs synthesis of authentic viral polypeptides in a linked transcription-translation cell-free system.", "content": "A linked cell-free system has been developed which is capable of transcribing and translating mamalian viral DNA, and its characteristics and requirements are outlined. In this system, simian virus 40 (SV40) DNA Form I (supercoiled) directed the synthesis of discrete polypeptides up to 85,000 daltons in size. One of these products was indistingusihable from authentic major virus capsid protein VPI, as judged by mobility on sodium dodecyl sulfate/polyacrylamide gels, antibody predipitation, and peptide analyses. The cell-free products larger than VPI comprised a number of polypeptides ranging in molecular weight from 50,000 to 85,000. These polypeptides demonstrated no immunological relationship whatsoever to the structural protein VPI. However, two of these products, along with one of approximately 25,000 dlatons, were precipitated with antiserum to SV40 tumor antigen. Linear SV40 DNA generated by the cleavage of Form I DNA with the restriction endonuclease EcoR1 was an efficient template in this system and also directed the synthesis of a polypeptide migrating with VPI on polyacrylamide gels. The potential of this system for defining a functional map of a DNA genome is discussed.", "contents": "Simian virus 40 DNA directs synthesis of authentic viral polypeptides in a linked transcription-translation cell-free system. A linked cell-free system has been developed which is capable of transcribing and translating mamalian viral DNA, and its characteristics and requirements are outlined. In this system, simian virus 40 (SV40) DNA Form I (supercoiled) directed the synthesis of discrete polypeptides up to 85,000 daltons in size. One of these products was indistingusihable from authentic major virus capsid protein VPI, as judged by mobility on sodium dodecyl sulfate/polyacrylamide gels, antibody predipitation, and peptide analyses. The cell-free products larger than VPI comprised a number of polypeptides ranging in molecular weight from 50,000 to 85,000. These polypeptides demonstrated no immunological relationship whatsoever to the structural protein VPI. However, two of these products, along with one of approximately 25,000 dlatons, were precipitated with antiserum to SV40 tumor antigen. Linear SV40 DNA generated by the cleavage of Form I DNA with the restriction endonuclease EcoR1 was an efficient template in this system and also directed the synthesis of a polypeptide migrating with VPI on polyacrylamide gels. The potential of this system for defining a functional map of a DNA genome is discussed."} {"id": "PMID:168583", "title": "Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1).", "content": "Six biochemically differentiated clonal lines have been established from a transplantable glioma (tg26) of the C57BL/6 inbred mouse strain. Antibodies have been previously raised against G26 tumor cells, which define a cell surface component(s), NS-1 (nervous system antigen-1), found exclusively in the nervous system. NS-1 concentrations approximate the levels of the original G26 tumor when the clonal lines are grown as clonal tumors in vivo, but are reduced when the cells are grown in vitro. NS-1 concentrations are further reduced in vitro upon incubation of the cells with 1 mM dibutyryl 3:5-cyclic AMP. H-2 histocompatibility antigen concentration, in contrast, is unaffected by dibutyryl cAMP. In addition to expressing NS-1, the neuroectodermal origin of these cell lines is further confirmed by their synthesis of the nervous system specific acidic protein S-100 and by the high specific activity of the enzyme 2:3-cyclic nucleotide 3-phosphohydrolase. In addition, they respond to catecholamines by the elevation of intracellular 3:5-cyclic AMP levels. Whereas expression of S-100 protein is high under in vitro conditions but negligible after one passage in vivo, 2:3-cyclic nucleotide 3-phosphohydrolase is not detectable in vitro but becomes detectable again in vivo. The two membrane-bound constituents, NS-1 and 2:3-cyclic nucleotide 3-phosphohydrolase, therefore seem to be subjected to different regulatory mechanisms from that of the soluble, intracellular S-100 protein.", "contents": "Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1). Six biochemically differentiated clonal lines have been established from a transplantable glioma (tg26) of the C57BL/6 inbred mouse strain. Antibodies have been previously raised against G26 tumor cells, which define a cell surface component(s), NS-1 (nervous system antigen-1), found exclusively in the nervous system. NS-1 concentrations approximate the levels of the original G26 tumor when the clonal lines are grown as clonal tumors in vivo, but are reduced when the cells are grown in vitro. NS-1 concentrations are further reduced in vitro upon incubation of the cells with 1 mM dibutyryl 3:5-cyclic AMP. H-2 histocompatibility antigen concentration, in contrast, is unaffected by dibutyryl cAMP. In addition to expressing NS-1, the neuroectodermal origin of these cell lines is further confirmed by their synthesis of the nervous system specific acidic protein S-100 and by the high specific activity of the enzyme 2:3-cyclic nucleotide 3-phosphohydrolase. In addition, they respond to catecholamines by the elevation of intracellular 3:5-cyclic AMP levels. Whereas expression of S-100 protein is high under in vitro conditions but negligible after one passage in vivo, 2:3-cyclic nucleotide 3-phosphohydrolase is not detectable in vitro but becomes detectable again in vivo. The two membrane-bound constituents, NS-1 and 2:3-cyclic nucleotide 3-phosphohydrolase, therefore seem to be subjected to different regulatory mechanisms from that of the soluble, intracellular S-100 protein."} {"id": "PMID:168584", "title": "In vitro transformation of lymphoid cells by Abelson murine leukemia virus.", "content": "Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus. After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures. Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells. Immunoglobulin determinants were evident on the cells in some cultures. Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation. Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control.", "contents": "In vitro transformation of lymphoid cells by Abelson murine leukemia virus. Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus. After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures. Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells. Immunoglobulin determinants were evident on the cells in some cultures. Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation. Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control."} {"id": "PMID:168585", "title": "Interaction of partially purified simian virus 40 T antigen with circular viral DNA molecules.", "content": "Mixing chromatographic fractions containing simian virus 40 (SV40) T antigen with SV40 [3H]-DNA I (double-stranded, circular, supercoiled) results in the conversion of the nucleic acid to a form that will bind to a nitrocellulose filter. Unlabeled SV40 DNA I successfully competes with this reaction. Under the conditions employed, the antigen-containing fractions bind a variety of circular, viral DNA molecules. Chromatography of the antigen in three systems reveals that the T immunoreactivity migrates with DNA binding activity. In a kinetic heat inactivation experiment, the antigenic reactivity disappears simultaneously with the DNA binding activity. The data indicate the presence of a discernible DNA binding activity in fractions containing T antigen and suggest that the T antigen is the DNA binding protein being measured.", "contents": "Interaction of partially purified simian virus 40 T antigen with circular viral DNA molecules. Mixing chromatographic fractions containing simian virus 40 (SV40) T antigen with SV40 [3H]-DNA I (double-stranded, circular, supercoiled) results in the conversion of the nucleic acid to a form that will bind to a nitrocellulose filter. Unlabeled SV40 DNA I successfully competes with this reaction. Under the conditions employed, the antigen-containing fractions bind a variety of circular, viral DNA molecules. Chromatography of the antigen in three systems reveals that the T immunoreactivity migrates with DNA binding activity. In a kinetic heat inactivation experiment, the antigenic reactivity disappears simultaneously with the DNA binding activity. The data indicate the presence of a discernible DNA binding activity in fractions containing T antigen and suggest that the T antigen is the DNA binding protein being measured."} {"id": "PMID:168586", "title": "Role of bovine albumin in a serum-free suspension cell culture medium.", "content": "A serum-free culture medium, supplemented with 1% bovine serum albumin, supported the growth of both primary and continuous suspension-type cultures of various mammalian tumor cells. The role of albumin added to the medium was also studied. Defatted albumin failed to support cell growth, unless reconstituted with its lipid extract. Similarly, defatted albumin when combined with oleic and linoleic acids, also supported cell growth. Therefore, albumin-bound fatty acids play an important growth-promoting role in serum-free medium.", "contents": "Role of bovine albumin in a serum-free suspension cell culture medium. A serum-free culture medium, supplemented with 1% bovine serum albumin, supported the growth of both primary and continuous suspension-type cultures of various mammalian tumor cells. The role of albumin added to the medium was also studied. Defatted albumin failed to support cell growth, unless reconstituted with its lipid extract. Similarly, defatted albumin when combined with oleic and linoleic acids, also supported cell growth. Therefore, albumin-bound fatty acids play an important growth-promoting role in serum-free medium."} {"id": "PMID:168587", "title": "Correlation of survival from murine cytomegalovirus infection with spleen cell responsiveness to Concanavallin A.", "content": "Spleen cells from nonlethally MCMV-infected weanling and adult DBA/2 mice had diminished responses to Con A stimulation. In contrast, only lethal MCMV infections were associated with a complete suppression of the Con A response. The immune response to SRBC was depressed even in asymptomatic infections of weanling and adult mice. A marked maturation of resistance to the lethal effects of MCMV infection was found to occur during the fourth week of life.", "contents": "Correlation of survival from murine cytomegalovirus infection with spleen cell responsiveness to Concanavallin A. Spleen cells from nonlethally MCMV-infected weanling and adult DBA/2 mice had diminished responses to Con A stimulation. In contrast, only lethal MCMV infections were associated with a complete suppression of the Con A response. The immune response to SRBC was depressed even in asymptomatic infections of weanling and adult mice. A marked maturation of resistance to the lethal effects of MCMV infection was found to occur during the fourth week of life."} {"id": "PMID:168588", "title": "Lipids and cell fusion in vitro: effect of amphotericin B.", "content": "Fusion rate of Cl-1D cells mediated by Sendai virus was decreased by preincubating the cells or the virus in the presence of lysolecithin. However, a significant increase occurred when the cells were preincubated in the presence of amphotericin B. This increase was suppressed by exogenous cholesterol.", "contents": "Lipids and cell fusion in vitro: effect of amphotericin B. Fusion rate of Cl-1D cells mediated by Sendai virus was decreased by preincubating the cells or the virus in the presence of lysolecithin. However, a significant increase occurred when the cells were preincubated in the presence of amphotericin B. This increase was suppressed by exogenous cholesterol."} {"id": "PMID:168589", "title": "DES-ASP1--angiotensin II: possible role in mediating responses of the renin-angiotensin system.", "content": "In dexamethasone-treated dogs, both antiogensin II and its heptapeptide fragment (des-asp1-angiotensin II) stimulated the secretion of the adrenal steroids aldosterone, corticosterone, and cortisol. Further, there was no statistically significant difference in the steroidogenic potency of the two peptides. An interesting incidental finding was the decrease in PRA with both peptides, again with no demonstrable difference in the magnitude of the responses. The present data are consistent with the hypothesis that the heptapeptide mediates responses produced by the renin-angiotensin system in both the adrenals and the kidneys.", "contents": "DES-ASP1--angiotensin II: possible role in mediating responses of the renin-angiotensin system. In dexamethasone-treated dogs, both antiogensin II and its heptapeptide fragment (des-asp1-angiotensin II) stimulated the secretion of the adrenal steroids aldosterone, corticosterone, and cortisol. Further, there was no statistically significant difference in the steroidogenic potency of the two peptides. An interesting incidental finding was the decrease in PRA with both peptides, again with no demonstrable difference in the magnitude of the responses. The present data are consistent with the hypothesis that the heptapeptide mediates responses produced by the renin-angiotensin system in both the adrenals and the kidneys."} {"id": "PMID:168590", "title": "Effect of lithium ions on RNA synthesis in mammary gland explants of mice.", "content": "LiC1 was found to stimulate RNA synthesis in the mammary gland in a manner similar to that of prolactin. Since LiC1 is known to inhibit adenyl cyclase and thus to reduce levels of cyclic AMP, it is concluded that a reduced level of cyclic AMP may be one step in the mechanism whereby prolactin regulates the metabolism of the mammary gland.", "contents": "Effect of lithium ions on RNA synthesis in mammary gland explants of mice. LiC1 was found to stimulate RNA synthesis in the mammary gland in a manner similar to that of prolactin. Since LiC1 is known to inhibit adenyl cyclase and thus to reduce levels of cyclic AMP, it is concluded that a reduced level of cyclic AMP may be one step in the mechanism whereby prolactin regulates the metabolism of the mammary gland."} {"id": "PMID:168591", "title": "Brain catecholamines, spontaneous bioelectrical activity and aggressive behavior in ants (Formica rufa).", "content": "The effects of dopamine (DA), 1-DOPA, diethyldithiocarbamate (DDTC) and haloperidol on aggressive behavior and spontaneous bioelectrical activity of the ant (Formica rufa) were studied. Drugs such as DA, 1-DOPA and DDTC increased mutual aggressivity in ants while it failed to change aggression directed towards other species of insects (e.g., the beetle Geotrupes sp.). The amplitude of EEG waves and the amplitude of neuronal discharges within the protocerebrum decreased after administration of both DA and 1-DOPA. Both DDTC and 1-DOPA increased the concentration of adrenaline as well as DA in the brain of ants. Haloperidol decreased intrageneric aggressivity but caused no evident changes in both EEG pattern and neuronal discharges. The present study indicates that catecholamines are critically involved in the organization of aggressive behavior in ants.", "contents": "Brain catecholamines, spontaneous bioelectrical activity and aggressive behavior in ants (Formica rufa). The effects of dopamine (DA), 1-DOPA, diethyldithiocarbamate (DDTC) and haloperidol on aggressive behavior and spontaneous bioelectrical activity of the ant (Formica rufa) were studied. Drugs such as DA, 1-DOPA and DDTC increased mutual aggressivity in ants while it failed to change aggression directed towards other species of insects (e.g., the beetle Geotrupes sp.). The amplitude of EEG waves and the amplitude of neuronal discharges within the protocerebrum decreased after administration of both DA and 1-DOPA. Both DDTC and 1-DOPA increased the concentration of adrenaline as well as DA in the brain of ants. Haloperidol decreased intrageneric aggressivity but caused no evident changes in both EEG pattern and neuronal discharges. The present study indicates that catecholamines are critically involved in the organization of aggressive behavior in ants."} {"id": "PMID:168592", "title": "Noradrenergic role in the self-administration of morphine or amphetamine.", "content": "The role of brain noradrenergic neurons in mediating the reinforcing properties of small intravenous doses of morphine and d-amphetamine was investigated by pretreatment of rats with the norepinephrine-depleting agents diethyldithiocarbamate and U-14,624, inhibitors of dopamine-beta-hydroxylase (DBH). Such treatment prevented the reacquisition of a self-administration response (bar-press) for morphine (32 mug/kg/injection) or d-amphetamine (15 mug/kg/injection) made available on a CRF schedule. Pretreatment with a DBH inhibitor also prevented the development of a secondary (conditioned) reinforcer based on primary reinforcement assosiated with either drug. Observations indicating that the orienting reflex was intact are taken as evidence that depressant effects of the DBH inhibitors were not severe enough to disrupt the associative process. Therefore, any effect on learning does not seem sufficient to explain the present results. Thus, it is inferred that the mechanisms mediating reinforcement for both morphine and amphetamine were disrupted by the inhibition of central noradrenergic functions.", "contents": "Noradrenergic role in the self-administration of morphine or amphetamine. The role of brain noradrenergic neurons in mediating the reinforcing properties of small intravenous doses of morphine and d-amphetamine was investigated by pretreatment of rats with the norepinephrine-depleting agents diethyldithiocarbamate and U-14,624, inhibitors of dopamine-beta-hydroxylase (DBH). Such treatment prevented the reacquisition of a self-administration response (bar-press) for morphine (32 mug/kg/injection) or d-amphetamine (15 mug/kg/injection) made available on a CRF schedule. Pretreatment with a DBH inhibitor also prevented the development of a secondary (conditioned) reinforcer based on primary reinforcement assosiated with either drug. Observations indicating that the orienting reflex was intact are taken as evidence that depressant effects of the DBH inhibitors were not severe enough to disrupt the associative process. Therefore, any effect on learning does not seem sufficient to explain the present results. Thus, it is inferred that the mechanisms mediating reinforcement for both morphine and amphetamine were disrupted by the inhibition of central noradrenergic functions."} {"id": "PMID:168596", "title": "Effects of arterial hypoxemia and splenic nerve stimulation on myocardial adenosine 3',5'-Monophosphate in dogs.", "content": "Epinephrine infusion, 5-percent oxygen breathing, and splenic nerve stimulation were employed to increase cardiac output by 50-100% in anesthetized dogs. Epinephrine infusion as expected, increased plasma and myocardial cyclic AMP concentrations. Arterial hypoxemia increased cyclic AMP concentration in plasma but not in the heart. Practolol pretreatment abolished the increase in plasma cyclic AMP concentration and reduced the rise in cardiac output during hypoxemia. Splenic nerve stimulation was not associated with increases in either plasma or myocardial cyclic AMP. Adenylate cyclase activity was increased by addition of plasma into the incubation medium. However, splenic venous plasma obtained during splenic nerve stimulation did not increase adenylate cyclase activity more than control plasma obtained before stimulation. We conclude that the positive inotropic action of arterial hypoxemia and splenic nerve stimulation does not depend on the adenylate cyclase-cyclic AMP system.", "contents": "Effects of arterial hypoxemia and splenic nerve stimulation on myocardial adenosine 3',5'-Monophosphate in dogs. Epinephrine infusion, 5-percent oxygen breathing, and splenic nerve stimulation were employed to increase cardiac output by 50-100% in anesthetized dogs. Epinephrine infusion as expected, increased plasma and myocardial cyclic AMP concentrations. Arterial hypoxemia increased cyclic AMP concentration in plasma but not in the heart. Practolol pretreatment abolished the increase in plasma cyclic AMP concentration and reduced the rise in cardiac output during hypoxemia. Splenic nerve stimulation was not associated with increases in either plasma or myocardial cyclic AMP. Adenylate cyclase activity was increased by addition of plasma into the incubation medium. However, splenic venous plasma obtained during splenic nerve stimulation did not increase adenylate cyclase activity more than control plasma obtained before stimulation. We conclude that the positive inotropic action of arterial hypoxemia and splenic nerve stimulation does not depend on the adenylate cyclase-cyclic AMP system."} {"id": "PMID:168593", "title": "Evidence for adrenergic neurons in a memory access pathway.", "content": "Injection of a beta-adrenergic blocker, propranolol, in rats within 5 min after training of a step-dowm passive avoidance response had no effect on performance either 2 or 6 hr later, however, when testing occurred 1, 3 or 7 days after training and injection a significant performance decrement was observed. If drug injection was postponed until 1 or 3 days after training and testing was conducted 2 hr later, again poor avoidance performance was obtained. No support for a state-dependency explanation [14] of the propranolol amnesia could be found. The amnesia that followed beta-adrenergic receptor block was identical to that previously reported when norepinephrine biosynthesis was reduced [9] and supports the hypothesis of a role for adrenergic neurons in memory formation and retrieval that is different from cholinergic neurons [4,10].", "contents": "Evidence for adrenergic neurons in a memory access pathway. Injection of a beta-adrenergic blocker, propranolol, in rats within 5 min after training of a step-dowm passive avoidance response had no effect on performance either 2 or 6 hr later, however, when testing occurred 1, 3 or 7 days after training and injection a significant performance decrement was observed. If drug injection was postponed until 1 or 3 days after training and testing was conducted 2 hr later, again poor avoidance performance was obtained. No support for a state-dependency explanation [14] of the propranolol amnesia could be found. The amnesia that followed beta-adrenergic receptor block was identical to that previously reported when norepinephrine biosynthesis was reduced [9] and supports the hypothesis of a role for adrenergic neurons in memory formation and retrieval that is different from cholinergic neurons [4,10]."} {"id": "PMID:168597", "title": "Anti-prostaglandin action of colchicine.", "content": "Colchicine, given locally, inhibits urate-crystal- and CaPPD-crystal-induced inflammation. Since this inflammation is known to be mediated in part by PGE1 these observations indicate colchicine acts as an anti-PG agent. Colchicine counteracts the phlogistic action of exogenous PGE1 in both urate- and CaPPD-crystal-induced inflammation. With use of large excesses of colchicine, its anti-inflammatory action appears limited to its anti-PGE1 activity. In turn, PGE1 counteracts the antiphlogistic action of colchicine. Colchicine is less effective in reducing swelling due to CaPPD-crystals than that due to urate-crystals, a finding similar to the clinical observations that colchicine is more effective therapy for gout than for pseudogout. Some relationships are reviewed to suggest that CaPPD-crystal inflammation is a more severe membrane disorder than is urate-crystal inflammation.", "contents": "Anti-prostaglandin action of colchicine. Colchicine, given locally, inhibits urate-crystal- and CaPPD-crystal-induced inflammation. Since this inflammation is known to be mediated in part by PGE1 these observations indicate colchicine acts as an anti-PG agent. Colchicine counteracts the phlogistic action of exogenous PGE1 in both urate- and CaPPD-crystal-induced inflammation. With use of large excesses of colchicine, its anti-inflammatory action appears limited to its anti-PGE1 activity. In turn, PGE1 counteracts the antiphlogistic action of colchicine. Colchicine is less effective in reducing swelling due to CaPPD-crystals than that due to urate-crystals, a finding similar to the clinical observations that colchicine is more effective therapy for gout than for pseudogout. Some relationships are reviewed to suggest that CaPPD-crystal inflammation is a more severe membrane disorder than is urate-crystal inflammation."} {"id": "PMID:168598", "title": "Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection.", "content": "The ability of ascorbic acid, sodium salicylate, and caffeine to alter the circulating serum level of interferon was investigated in mice. The animals were singly injected subcutaneously with one of the compounds, 4-8 h later again singly injected intraperitoneally with poly I:C, and bled 6-8 h afterward. The sera from the mice were assayed for interferon titer by the use of the plaque inhibition method utilizing vesicular stomatitis virus. Ascorbic acid, sodium salicylate, and caffeine increased the serum level of interferon; however, the increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. Caffeine produced minimal increases in the interferon titer. These observations suggest that a potential prophylactic result may occur in virus infections from administration of the three compounds either singly or in combination at the proper concentration.", "contents": "Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection. The ability of ascorbic acid, sodium salicylate, and caffeine to alter the circulating serum level of interferon was investigated in mice. The animals were singly injected subcutaneously with one of the compounds, 4-8 h later again singly injected intraperitoneally with poly I:C, and bled 6-8 h afterward. The sera from the mice were assayed for interferon titer by the use of the plaque inhibition method utilizing vesicular stomatitis virus. Ascorbic acid, sodium salicylate, and caffeine increased the serum level of interferon; however, the increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. Caffeine produced minimal increases in the interferon titer. These observations suggest that a potential prophylactic result may occur in virus infections from administration of the three compounds either singly or in combination at the proper concentration."} {"id": "PMID:168599", "title": "Free radical evolution in rat liver following the ingestion of DAB.", "content": "The effect of the ingestion of the carcinogenic substance DAB on the density and distribution of organic free radicals in rat liver is studied by the electron spin resonance method. There is a remarkable parallelism between what is known about the evolution of the activity of mitochondria and the concentration variations of free radicals.", "contents": "Free radical evolution in rat liver following the ingestion of DAB. The effect of the ingestion of the carcinogenic substance DAB on the density and distribution of organic free radicals in rat liver is studied by the electron spin resonance method. There is a remarkable parallelism between what is known about the evolution of the activity of mitochondria and the concentration variations of free radicals."} {"id": "PMID:168600", "title": "Caudate nucleus lesion selectively increases paradoxical sleep episodes in the rat.", "content": "The EMG, ECG and the behavioral activity of seven rats were recorded for three days previous to and 24 hours after lesioning both caudate-putamen complexes. Following the lesion, the paradoxical sleep stage lengthened by about 248%, without noticeable changes in the slow wave sleep or in the waking stages. The greatest increase was obtained with lesions placed in the mediomedial portion of the caudate-putamen complex. In other six rats submitted to the above procedure except that the lesions were placed in the anterior cerebral cortex, and also in five more rats implanted in both caudate-putamen complexes but not lesioned, no change was noted in the waking, paradoxical sleep or slow wave sleep stages.", "contents": "Caudate nucleus lesion selectively increases paradoxical sleep episodes in the rat. The EMG, ECG and the behavioral activity of seven rats were recorded for three days previous to and 24 hours after lesioning both caudate-putamen complexes. Following the lesion, the paradoxical sleep stage lengthened by about 248%, without noticeable changes in the slow wave sleep or in the waking stages. The greatest increase was obtained with lesions placed in the mediomedial portion of the caudate-putamen complex. In other six rats submitted to the above procedure except that the lesions were placed in the anterior cerebral cortex, and also in five more rats implanted in both caudate-putamen complexes but not lesioned, no change was noted in the waking, paradoxical sleep or slow wave sleep stages."} {"id": "PMID:168604", "title": "Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol.", "content": "The pharmacological activities of delta9-THC [(minus)-delta9-trans-tetrahydrocannabinol], CBN (Cannabinol) and mixtures of delta9-THC + CBN were studied in rabbits, rats and mice. CBN, although in general less active, mimicked the effects of delta9-THC in several pharmacological tests: corneal arreflexia in rabbits; climbing rope, open-field, irritability and aggressiveness after REM sleep deprivation in rats; catatonia, analgesia and sleeping time in mice. When the mixture delta9-THC + CBN was used, a synergistic effect occurred on most of the depressant effects. On the other hand CBN did not interfere with or slightly inhibited the excitatory effects of delta9-THC. In the one peripheral test used, CBN did not alter the delta9-THC effect.", "contents": "Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol. The pharmacological activities of delta9-THC [(minus)-delta9-trans-tetrahydrocannabinol], CBN (Cannabinol) and mixtures of delta9-THC + CBN were studied in rabbits, rats and mice. CBN, although in general less active, mimicked the effects of delta9-THC in several pharmacological tests: corneal arreflexia in rabbits; climbing rope, open-field, irritability and aggressiveness after REM sleep deprivation in rats; catatonia, analgesia and sleeping time in mice. When the mixture delta9-THC + CBN was used, a synergistic effect occurred on most of the depressant effects. On the other hand CBN did not interfere with or slightly inhibited the excitatory effects of delta9-THC. In the one peripheral test used, CBN did not alter the delta9-THC effect."} {"id": "PMID:168605", "title": "Retroactive impairment of cooperative learning by imipramine and chlordiazepoxide in rats.", "content": "Pairs of rats were placed in an apparatus where their sole food source hung over an electrified grid. The current was shut off only while one rat remained on a platform out of reach of the food, thus allowing his partner to eat. Mastery of the process of taking turns at eating required about 10 daily sessions. Injection of imipramine or chlordiazepoxide a few minutes after each feeding session prevented the development of this cooperative behavior. Drug injection 3 hrs after each session had no effect. Suppression of REM sleep during the first 3 hrs after training was considered the most likely mechanism of the drug-induced impairment.", "contents": "Retroactive impairment of cooperative learning by imipramine and chlordiazepoxide in rats. Pairs of rats were placed in an apparatus where their sole food source hung over an electrified grid. The current was shut off only while one rat remained on a platform out of reach of the food, thus allowing his partner to eat. Mastery of the process of taking turns at eating required about 10 daily sessions. Injection of imipramine or chlordiazepoxide a few minutes after each feeding session prevented the development of this cooperative behavior. Drug injection 3 hrs after each session had no effect. Suppression of REM sleep during the first 3 hrs after training was considered the most likely mechanism of the drug-induced impairment."} {"id": "PMID:168606", "title": "Effects of early post-natal alpha-methyl-dopa treatment on behavior in the rat.", "content": "250 mg/kg of L-alpha-methyl-Dopa (alpha-m-Dopa) or saline were administered to rats for three weeks after birth. Subsequent tests revealed an increased locomotor activity and greater rate of acquisition but no disturbance in shuttle-box conditioning. The whole brain content of norepinephrine, dopamine and serotonin was not affected.", "contents": "Effects of early post-natal alpha-methyl-dopa treatment on behavior in the rat. 250 mg/kg of L-alpha-methyl-Dopa (alpha-m-Dopa) or saline were administered to rats for three weeks after birth. Subsequent tests revealed an increased locomotor activity and greater rate of acquisition but no disturbance in shuttle-box conditioning. The whole brain content of norepinephrine, dopamine and serotonin was not affected."} {"id": "PMID:168611", "title": "[Behavior of lipoprotein X (LP-X) in viral hepatitis].", "content": "The AA. have studied the behaviour of LP-X in fifty cases of viral hepatitis printing out a positivity in 32% of the examined cases, with a positivity of the Au-antigen in the 34% of cases. They have observed a more remarkable inclination to the cholostasis in children (40% of the cases of positivity of LP-X), concluding for a scarce specificity of such a \"marker\" of cholostasis.", "contents": "[Behavior of lipoprotein X (LP-X) in viral hepatitis]. The AA. have studied the behaviour of LP-X in fifty cases of viral hepatitis printing out a positivity in 32% of the examined cases, with a positivity of the Au-antigen in the 34% of cases. They have observed a more remarkable inclination to the cholostasis in children (40% of the cases of positivity of LP-X), concluding for a scarce specificity of such a \"marker\" of cholostasis."} {"id": "PMID:168614", "title": "Early experience with the EMI scanner for study of the brain.", "content": "Computed tomography of the head is highly accurate new radiologic technique for the evaluation of neurologic disease. Analysis of early cases indicates that the appearance produced by CT in some conditions is unique and that increasing experience allows the neuroradiologist to predict the position and nature of disease processes with greater accuracy.", "contents": "Early experience with the EMI scanner for study of the brain. Computed tomography of the head is highly accurate new radiologic technique for the evaluation of neurologic disease. Analysis of early cases indicates that the appearance produced by CT in some conditions is unique and that increasing experience allows the neuroradiologist to predict the position and nature of disease processes with greater accuracy."} {"id": "PMID:168615", "title": "Myelographic cervical nerve root deformities.", "content": "Myelograms of nerve roots and adjacent subarachnoid space were reviewed to characterize 231 cervical root deformities from both symptomatic and asymptomatic patients. Good correlation between specific features of root deformities and clinical significance could not be demonstrated. Some features were slightly suggestive of clinical significance but occurred in a sufficient number of asymptomatic patients to make them unreliable. The most accurate determinants of root deformity significance are clincal and electromyographic findings.", "contents": "Myelographic cervical nerve root deformities. Myelograms of nerve roots and adjacent subarachnoid space were reviewed to characterize 231 cervical root deformities from both symptomatic and asymptomatic patients. Good correlation between specific features of root deformities and clinical significance could not be demonstrated. Some features were slightly suggestive of clinical significance but occurred in a sufficient number of asymptomatic patients to make them unreliable. The most accurate determinants of root deformity significance are clincal and electromyographic findings."} {"id": "PMID:168616", "title": "Retrograde hepatography and indirect lymphography of the liver: an experimental study in the dog.", "content": "Retrograde infusion of large amounts of water-soluble contrast agents into the biliary system results in only a brief hepatogram. A dense hepatogram lasting for several weeks and visualization of hepatic and celiac lymph nodes equal to that in direct lymphography can be obtained after retrograde biliary infusion of Ethiodol. In serching for metastasis from tumor in the liver, gall-bladder, bile ducts, pancreas, stomach, and duodenum, radiographic visualization of these nodes may help. If proved safe, the procedure can be performed by endocopic cannulation of the common bile duct.", "contents": "Retrograde hepatography and indirect lymphography of the liver: an experimental study in the dog. Retrograde infusion of large amounts of water-soluble contrast agents into the biliary system results in only a brief hepatogram. A dense hepatogram lasting for several weeks and visualization of hepatic and celiac lymph nodes equal to that in direct lymphography can be obtained after retrograde biliary infusion of Ethiodol. In serching for metastasis from tumor in the liver, gall-bladder, bile ducts, pancreas, stomach, and duodenum, radiographic visualization of these nodes may help. If proved safe, the procedure can be performed by endocopic cannulation of the common bile duct."} {"id": "PMID:168617", "title": "Congenital asymmetry (hemihypertrophy) and abdominal disease: radiological features in 9 cases.", "content": "Coexistent abdominal disease was found in 9 cases of congenital asymmetry. These patients appear to be at risk of malignant neoplasms of the adrenal gland, kidney, and liver. Five of the 6 neoplasms in this group of patients were malignant. Approximately 25% of the reported cases of hemihypertrophy have been associated with hamartomas or congenital defects, especially genitourinary anomalies. Benign disorders encountered in this group included medullary sponge kidney, renal ectopia, renal cyst, nephromegaly, adrenomegaly, and hypospadius.", "contents": "Congenital asymmetry (hemihypertrophy) and abdominal disease: radiological features in 9 cases. Coexistent abdominal disease was found in 9 cases of congenital asymmetry. These patients appear to be at risk of malignant neoplasms of the adrenal gland, kidney, and liver. Five of the 6 neoplasms in this group of patients were malignant. Approximately 25% of the reported cases of hemihypertrophy have been associated with hamartomas or congenital defects, especially genitourinary anomalies. Benign disorders encountered in this group included medullary sponge kidney, renal ectopia, renal cyst, nephromegaly, adrenomegaly, and hypospadius."} {"id": "PMID:168618", "title": "Steroid hormone modulation of 3H-prostaglanding E1 binding to bovine corpus leteum cell membranes.", "content": "The specific binding of 3H-prostaglandin E1 (3H-PGE1) to bovine corpus luteum cell membranes was not affected by cholesterol or various progestins at concentrations of up to 9.0x10-minus-6M. At concentrations above 2.5 x 10-minus-6M; estrone, 17beta-estradiol (but not 17alpha-estradiol or 17beta-estradiol glucuronide), estroil, equilin, D-equilenin, 17-ethynyl estradiol, diethylstilbestrol, cortisol, corticosterone, deoxycorticosterone and aldosterone inhibited specific binding of 3H-PGE1. On the other hand, testosterone and dihydrotestosterone (DHT) (but not androstenedione) significantly enhanced 3H-PGE1 binding. These findings permitted the following correlations between steroid structure and modulation of 3H-PGE1 binding: steroids with a free phenolic ring and a 17beta-hydroxyl or 17-keto group or C-21 steroids with a C-20 ketone and a C-21 hydroxy group decrease, whereas C-19 steroids with a C-17 hydroxy group enhance specific binding of 3H-PGE1. PGE receptors are heterogeneous with respect to affinity for 3H-PGE1. The steroids that decreased 3H-PGE1 binding caused a lowering to a complete loss of low affinity PGE receptors. Steroids that increased 3H-PGE1 binding caused appearance of new low affinity PGE receptors. Association rate constants for 3H-PGE1 binding were decreased by 17beta-estradiol (61%) and increased by DHT (59%).", "contents": "Steroid hormone modulation of 3H-prostaglanding E1 binding to bovine corpus leteum cell membranes. The specific binding of 3H-prostaglandin E1 (3H-PGE1) to bovine corpus luteum cell membranes was not affected by cholesterol or various progestins at concentrations of up to 9.0x10-minus-6M. At concentrations above 2.5 x 10-minus-6M; estrone, 17beta-estradiol (but not 17alpha-estradiol or 17beta-estradiol glucuronide), estroil, equilin, D-equilenin, 17-ethynyl estradiol, diethylstilbestrol, cortisol, corticosterone, deoxycorticosterone and aldosterone inhibited specific binding of 3H-PGE1. On the other hand, testosterone and dihydrotestosterone (DHT) (but not androstenedione) significantly enhanced 3H-PGE1 binding. These findings permitted the following correlations between steroid structure and modulation of 3H-PGE1 binding: steroids with a free phenolic ring and a 17beta-hydroxyl or 17-keto group or C-21 steroids with a C-20 ketone and a C-21 hydroxy group decrease, whereas C-19 steroids with a C-17 hydroxy group enhance specific binding of 3H-PGE1. PGE receptors are heterogeneous with respect to affinity for 3H-PGE1. The steroids that decreased 3H-PGE1 binding caused a lowering to a complete loss of low affinity PGE receptors. Steroids that increased 3H-PGE1 binding caused appearance of new low affinity PGE receptors. Association rate constants for 3H-PGE1 binding were decreased by 17beta-estradiol (61%) and increased by DHT (59%)."} {"id": "PMID:168620", "title": "A comparison of immunologic response to intranasal and intramuscular parainfluenza-3 live virus vaccines in beef calves challenged experimentally in the feedlot.", "content": "Feeder calves were vaccinated with modified live virus (MLV) bovine parainfluenza-3 (PI-3) vaccines by the nasal and parenteral routes. Thirty days later they were challenged with the SF-4 strain of virus. Serum hemagglutination-inhibition (HI) antibodies and neutralizing antibodies in nasal secretions were compared with unvaccinated control calves. Both vaccines produced satisfactory circulating antibodies, but intranasal vaccination produced higher levels of antibodies in nasal secretions. After challenge PI-3 virus was not isolated from the vaccinated calves or two contact control unvaccinated calves but was isolated from all unvaccinated control calves isolated from vaccinated calves.", "contents": "A comparison of immunologic response to intranasal and intramuscular parainfluenza-3 live virus vaccines in beef calves challenged experimentally in the feedlot. Feeder calves were vaccinated with modified live virus (MLV) bovine parainfluenza-3 (PI-3) vaccines by the nasal and parenteral routes. Thirty days later they were challenged with the SF-4 strain of virus. Serum hemagglutination-inhibition (HI) antibodies and neutralizing antibodies in nasal secretions were compared with unvaccinated control calves. Both vaccines produced satisfactory circulating antibodies, but intranasal vaccination produced higher levels of antibodies in nasal secretions. After challenge PI-3 virus was not isolated from the vaccinated calves or two contact control unvaccinated calves but was isolated from all unvaccinated control calves isolated from vaccinated calves."} {"id": "PMID:168621", "title": "Selective inhibition of nicotinamide adenine dinucleotide dependent oxidations by substituted carbamides.", "content": "Several 1-substituted acetyl-3-aryl carbamides selectively inhibited nicotinamide adenine dinucleotide (NAD) dependent oxidation of alpha-keotoglutarate and beta-hydroxybutyrate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. The inhibition observed with 1-(N-acetylmorpholino)-3-(4-methylphenyl)carbamide was competitive in nature.", "contents": "Selective inhibition of nicotinamide adenine dinucleotide dependent oxidations by substituted carbamides. Several 1-substituted acetyl-3-aryl carbamides selectively inhibited nicotinamide adenine dinucleotide (NAD) dependent oxidation of alpha-keotoglutarate and beta-hydroxybutyrate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. The inhibition observed with 1-(N-acetylmorpholino)-3-(4-methylphenyl)carbamide was competitive in nature."} {"id": "PMID:168623", "title": "The mode of inhibition of herpes simplex and vesicular stomatitis ocular viral infections in the rabbit and hamster by an interferon inducer tilorone dihydrochloride.", "content": "Ocular viral infections are a major cause of loss of vision and their effective control by applications of chemical compounds has been extensively investigated. To achieve such a control, better understanding of virus-host-drug interactions become a necessity. Two models, hamster and rabbit cornea, were selected for assays of protection afforded by tilorone dihydrochloride against herpes simplex (HSV) and vesicular stomatitis viruses (VSV). To obtain basic biologic comparison between viral interference and interferon-induction by tilorone, the hamster cornea system was first studied to produce a mutual viral interference by double infection. Furthermore, its effect against ascending herpetic ocular infection into encephalitis was evaluated in the rabbit. This compound was reported to have promising results in improving manifestations such as corneal ulceration, uveitis and conjunctivitis.", "contents": "The mode of inhibition of herpes simplex and vesicular stomatitis ocular viral infections in the rabbit and hamster by an interferon inducer tilorone dihydrochloride. Ocular viral infections are a major cause of loss of vision and their effective control by applications of chemical compounds has been extensively investigated. To achieve such a control, better understanding of virus-host-drug interactions become a necessity. Two models, hamster and rabbit cornea, were selected for assays of protection afforded by tilorone dihydrochloride against herpes simplex (HSV) and vesicular stomatitis viruses (VSV). To obtain basic biologic comparison between viral interference and interferon-induction by tilorone, the hamster cornea system was first studied to produce a mutual viral interference by double infection. Furthermore, its effect against ascending herpetic ocular infection into encephalitis was evaluated in the rabbit. This compound was reported to have promising results in improving manifestations such as corneal ulceration, uveitis and conjunctivitis."} {"id": "PMID:168624", "title": "REM sleep distributions in post-addict rats relapsing to morphine self-administration: effects of naloxone subcutaneous pellets.", "content": "Female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes and i.v. cannulas. They were administered i.v. injections of morphine to produce tolerance and physical dependence, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence. They were subsequently withdrawn for two weeks, implanted subcutaneously with one or two pellets of naloxone base, 100 mg each, or placebo pellets, returned to the experimental cages and allowed to relapse to self-administration of either saline or morphine. Rats with placebo pellets relapsed to morphine self-administration and reestablished the dependence state. However, rats implanted with naloxone and then permitted to self-administer morphine extinguished their lever pressing (\"drug-seeking behavior\"). Similar results were obtained with rats implanted with placebo pellets and self-administering saline. The self-injections of morphine by rats implanted with placebo pellets severely suppressed REM sleep and altered its normal distribution. Rats implanted with naloxone pellets and that subsequently extinguished their lever pressing, however, did not exhibit a change in REM sleep distributions. Similarly, self-injections of isotonic saline did not exert an effect on REM sleep distributions. These findings suggest that a correlation between REM sleep distributions, drug-seeking behavior, and morphine-naloxone interaction prevailed.", "contents": "REM sleep distributions in post-addict rats relapsing to morphine self-administration: effects of naloxone subcutaneous pellets. Female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes and i.v. cannulas. They were administered i.v. injections of morphine to produce tolerance and physical dependence, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence. They were subsequently withdrawn for two weeks, implanted subcutaneously with one or two pellets of naloxone base, 100 mg each, or placebo pellets, returned to the experimental cages and allowed to relapse to self-administration of either saline or morphine. Rats with placebo pellets relapsed to morphine self-administration and reestablished the dependence state. However, rats implanted with naloxone and then permitted to self-administer morphine extinguished their lever pressing (\"drug-seeking behavior\"). Similar results were obtained with rats implanted with placebo pellets and self-administering saline. The self-injections of morphine by rats implanted with placebo pellets severely suppressed REM sleep and altered its normal distribution. Rats implanted with naloxone pellets and that subsequently extinguished their lever pressing, however, did not exhibit a change in REM sleep distributions. Similarly, self-injections of isotonic saline did not exert an effect on REM sleep distributions. These findings suggest that a correlation between REM sleep distributions, drug-seeking behavior, and morphine-naloxone interaction prevailed."} {"id": "PMID:168625", "title": "Action of phenobarbital and carbon tetrachloride on hepatic microsomal inosine diphosphatase in the rat.", "content": "Pretreatment of rats with phenobarbital decreased the in vitro activity of liver microsomal inosine diphosphatase, whereas CCl4 caused an opposite effect. These actions were essentially abolished when the activity of the enzyme was assayed in the presence of optimal concentrations of triton X-100. The detergent was shown to activate and solubilize the enzyme along with membrane protein and phospholipids. During solubilization there was a tendency towards a greater phosphatidylcholine and lower phosphatidylethanolamine content in triton-soluble membranes. Microsomes of phenobarbital-treated rats were more resistant to triton solubilization, whereas those from CCl4-treated rats were more susceptible than the controls. These results demonstrated a loose association between the enzyme and the endoplasmic reticulum and that phenobarbital or CCl4 altered the activity of IDP-ase probably by affecting the binding of the enzyme to the structure skeleton of the membrane. The role of phospholipid changes in the stability of microsomal membranes is discussed.", "contents": "Action of phenobarbital and carbon tetrachloride on hepatic microsomal inosine diphosphatase in the rat. Pretreatment of rats with phenobarbital decreased the in vitro activity of liver microsomal inosine diphosphatase, whereas CCl4 caused an opposite effect. These actions were essentially abolished when the activity of the enzyme was assayed in the presence of optimal concentrations of triton X-100. The detergent was shown to activate and solubilize the enzyme along with membrane protein and phospholipids. During solubilization there was a tendency towards a greater phosphatidylcholine and lower phosphatidylethanolamine content in triton-soluble membranes. Microsomes of phenobarbital-treated rats were more resistant to triton solubilization, whereas those from CCl4-treated rats were more susceptible than the controls. These results demonstrated a loose association between the enzyme and the endoplasmic reticulum and that phenobarbital or CCl4 altered the activity of IDP-ase probably by affecting the binding of the enzyme to the structure skeleton of the membrane. The role of phospholipid changes in the stability of microsomal membranes is discussed."} {"id": "PMID:168626", "title": "Studies on immunisation of pigs with the Bartha strain of Aujeszky's disease virus.", "content": "The K strain of Aujeszky's disease virus (ADV) grown in Vero cells was used to vaccinate pigs. Following intramuscular inoculation, the pigs remained healthy, no vaccine virus was excreted and virus could be detected only at the inoculation site. One inoculation gave good protection against challenge with a virulent strain of ADV, and the amount of virulent ADV excreted was geatly curtailed. Following vaccination only low leads of serum neutralizing antibody were detected (geometric mean titre 1/2), but three weeks after challenge very high levels were found (GMT 1/1773). Intranasal vaccination gave similar results. There was minimal excretion of vaccine virus. The clinical reaction on challenge was less severe than in the intramuscularly challenged group, although lower antibody levels were detected three wekks following challenge (GMT 1/483). A field trial, using this strain given subcutaneously, indicated that one inoculation of this vaccine is effective.", "contents": "Studies on immunisation of pigs with the Bartha strain of Aujeszky's disease virus. The K strain of Aujeszky's disease virus (ADV) grown in Vero cells was used to vaccinate pigs. Following intramuscular inoculation, the pigs remained healthy, no vaccine virus was excreted and virus could be detected only at the inoculation site. One inoculation gave good protection against challenge with a virulent strain of ADV, and the amount of virulent ADV excreted was geatly curtailed. Following vaccination only low leads of serum neutralizing antibody were detected (geometric mean titre 1/2), but three weeks after challenge very high levels were found (GMT 1/1773). Intranasal vaccination gave similar results. There was minimal excretion of vaccine virus. The clinical reaction on challenge was less severe than in the intramuscularly challenged group, although lower antibody levels were detected three wekks following challenge (GMT 1/483). A field trial, using this strain given subcutaneously, indicated that one inoculation of this vaccine is effective."} {"id": "PMID:168627", "title": "Plasma progesterone levels in sows with induced cystic ovarian follicles.", "content": "Large multiple cystic ovarian follicles were induced in three sows and small multiple cystic ovarian follicles were induced in three other sows by injections of adrenocorticotrophic hormone (ACTH) during the follicular phase of the oestrous cycle. Plasma progesterone levels in sows with large cysts were relatively high, while those of sows with small cystic follicles were low. Removal of the ovaries with large cysts from one sow resulted in a precipitous drop in progesterone levels indicating that the large cysts were primarily the source of progesterone. The method by which ACTH may induced cystic ovaries was also investigated. Plasma progesterone levels in two ovariectomised sows during ACTH treatment fluctuated markedly during a 24 h period achieving peak values of 4 or 5 ng/ml. The results suggest that progesterone of adrenal cortical origin may be a factor in the development of the cystic ovarian condition.", "contents": "Plasma progesterone levels in sows with induced cystic ovarian follicles. Large multiple cystic ovarian follicles were induced in three sows and small multiple cystic ovarian follicles were induced in three other sows by injections of adrenocorticotrophic hormone (ACTH) during the follicular phase of the oestrous cycle. Plasma progesterone levels in sows with large cysts were relatively high, while those of sows with small cystic follicles were low. Removal of the ovaries with large cysts from one sow resulted in a precipitous drop in progesterone levels indicating that the large cysts were primarily the source of progesterone. The method by which ACTH may induced cystic ovaries was also investigated. Plasma progesterone levels in two ovariectomised sows during ACTH treatment fluctuated markedly during a 24 h period achieving peak values of 4 or 5 ng/ml. The results suggest that progesterone of adrenal cortical origin may be a factor in the development of the cystic ovarian condition."} {"id": "PMID:168628", "title": "The nasal secretion and serum antibody response of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.", "content": "The nasal and serum neutralising antibody responses of lambs was compared following vaccination with live or inactivated parainfluenza 3 (PI 3) virus by either intramuscular (IM) or intranasal (IN) routes. Nasal antibody was only detected following inoculation of live virus IN or inactivated virus in Freund's complete adjuvant (FCA) IM. Immunity to aerosol challenge, as assessed by viral shedding from the nose, was conferred by (1) live virus administered by either route, (2) two IM inoculations of inactivated virus in FCA, and (3) one IM injection of inactivated virus in FCA followed by IN instillation of inactivated virus.", "contents": "The nasal secretion and serum antibody response of lambs following vaccination and aerosol challenge with parainfluenza 3 virus. The nasal and serum neutralising antibody responses of lambs was compared following vaccination with live or inactivated parainfluenza 3 (PI 3) virus by either intramuscular (IM) or intranasal (IN) routes. Nasal antibody was only detected following inoculation of live virus IN or inactivated virus in Freund's complete adjuvant (FCA) IM. Immunity to aerosol challenge, as assessed by viral shedding from the nose, was conferred by (1) live virus administered by either route, (2) two IM inoculations of inactivated virus in FCA, and (3) one IM injection of inactivated virus in FCA followed by IN instillation of inactivated virus."} {"id": "PMID:168629", "title": "[Unusual association of a papillary cystadenoma and a mixed tumor of the parotid].", "content": "The authors describe the exceptional association within the same parotid gland of two oncologically different tumours. This provides them with material for discussion concerning the value of pre- and per-operative histological tests and leads them to put in a plea for total parotidectomy leaving the facial nerve intact.", "contents": "[Unusual association of a papillary cystadenoma and a mixed tumor of the parotid]. The authors describe the exceptional association within the same parotid gland of two oncologically different tumours. This provides them with material for discussion concerning the value of pre- and per-operative histological tests and leads them to put in a plea for total parotidectomy leaving the facial nerve intact."} {"id": "PMID:168630", "title": "[2 new cases of Klippel-Trenaunay syndrome].", "content": "After a brief account of the history and pathogeny, two cases are described of sub-angiomal bone hypo and hypertrophy. Other cases in the literature are recalled. Finally, a differential diagnosis is given.", "contents": "[2 new cases of Klippel-Trenaunay syndrome]. After a brief account of the history and pathogeny, two cases are described of sub-angiomal bone hypo and hypertrophy. Other cases in the literature are recalled. Finally, a differential diagnosis is given."} {"id": "PMID:168631", "title": "Effect of the carboxyl-terminal tripeptide of vasopressin on plasma free fatty acids and cyclic adenosine monophosphate in man.", "content": "The carboxyl-terminal tripeptide of casopressin (Pro-Arg-Gly.NH2) and adrenocorticotrophic hormone (ACTH) were injected intravenously into six human subjects, and the effects of these peptides on plasma free fatty acids (FFA) and cAMP concentrations were compared with that of saline. Twenty mug of the tripetide and 100 mug of ACTH INCREASED THE PLASMA FFA CONCENTRATION TO THE SAME EXTENT, WHEREAS 200 MUG OF THE TRIPETIDE WAS WITHOUT THIS LIPOLYTIC EFFECT. ACTH and the smaller dose of the tripeptide elevated the plasma cAMP level only in the same two subjects.", "contents": "Effect of the carboxyl-terminal tripeptide of vasopressin on plasma free fatty acids and cyclic adenosine monophosphate in man. The carboxyl-terminal tripeptide of casopressin (Pro-Arg-Gly.NH2) and adrenocorticotrophic hormone (ACTH) were injected intravenously into six human subjects, and the effects of these peptides on plasma free fatty acids (FFA) and cAMP concentrations were compared with that of saline. Twenty mug of the tripetide and 100 mug of ACTH INCREASED THE PLASMA FFA CONCENTRATION TO THE SAME EXTENT, WHEREAS 200 MUG OF THE TRIPETIDE WAS WITHOUT THIS LIPOLYTIC EFFECT. ACTH and the smaller dose of the tripeptide elevated the plasma cAMP level only in the same two subjects."} {"id": "PMID:168632", "title": "Clinical conditions associated with urinary excretion of 2-hydroxybutyric acid.", "content": "Urine and blood samples from patients with different clinical disorders were examined for 2-hydroxybutyric acid (2-HB) by gas chromatography and mass spectrometry. All patients with combined lactic acidosis and ketoacidosis excreted 2-HB in the urine, in amounts up to 2.3 mmol/mmol creatinine. In blood from these patients, 2-HB was present only in trace amounts. Hard physical exercise resulted in lactic acidosis and accumulation of 2-HB. The lactate to pyruvate ratio in blood and urine was markedly increased in the patients excreting 2-HB but was normal in two patients with lactic acidosis who did not excrete 2-HB. It is concluded that an increased NADH2/NAD ratio is the most important factor for the production of 2-HB.", "contents": "Clinical conditions associated with urinary excretion of 2-hydroxybutyric acid. Urine and blood samples from patients with different clinical disorders were examined for 2-hydroxybutyric acid (2-HB) by gas chromatography and mass spectrometry. All patients with combined lactic acidosis and ketoacidosis excreted 2-HB in the urine, in amounts up to 2.3 mmol/mmol creatinine. In blood from these patients, 2-HB was present only in trace amounts. Hard physical exercise resulted in lactic acidosis and accumulation of 2-HB. The lactate to pyruvate ratio in blood and urine was markedly increased in the patients excreting 2-HB but was normal in two patients with lactic acidosis who did not excrete 2-HB. It is concluded that an increased NADH2/NAD ratio is the most important factor for the production of 2-HB."} {"id": "PMID:168633", "title": "Depresssion in narcolepsy and hypersommia.", "content": "The authors studied the occurrence of depression in 100 randomly selected patients with narcolepsy and in 30 patients with hypersomnia. In the isolated form of idiopathic narcolepsy (without signs of cataplexy, sleep paralysis or hypnagogic hallucinations) depression occurred 28.6 per cent of cases. In idiopathic narcolepsy with cataplexy or other symptoms of sleep dissociation, depression was found in 17.2 per cent of cases. In idiopathic hypersomnia the occurrence of depression was 26.1 per cent. In the majority of cases the endogenous form of depression was observed. In the symptomatic form of narcolepsy and hypersomnia the occurence of depression has not been noted in any case. In most cases a parallel clincial course has been observed between the manifestation of depression and narcolepsy or hypersomnia. During a remission of the depressive state the hypersomniac symptoms decreased or disappeared totally. The authors furter discuss the possible pathophysiological mechanisms of the above mentioned symptoms. They are of the opinion that an important role is played by the secretion and metabolism of the cerebral monamines.", "contents": "Depresssion in narcolepsy and hypersommia. The authors studied the occurrence of depression in 100 randomly selected patients with narcolepsy and in 30 patients with hypersomnia. In the isolated form of idiopathic narcolepsy (without signs of cataplexy, sleep paralysis or hypnagogic hallucinations) depression occurred 28.6 per cent of cases. In idiopathic narcolepsy with cataplexy or other symptoms of sleep dissociation, depression was found in 17.2 per cent of cases. In idiopathic hypersomnia the occurrence of depression was 26.1 per cent. In the majority of cases the endogenous form of depression was observed. In the symptomatic form of narcolepsy and hypersomnia the occurence of depression has not been noted in any case. In most cases a parallel clincial course has been observed between the manifestation of depression and narcolepsy or hypersomnia. During a remission of the depressive state the hypersomniac symptoms decreased or disappeared totally. The authors furter discuss the possible pathophysiological mechanisms of the above mentioned symptoms. They are of the opinion that an important role is played by the secretion and metabolism of the cerebral monamines."} {"id": "PMID:168634", "title": "[Exophthalmogenic effect of thyrotropin releasing hormone (TRH) in the animal experiment].", "content": "Exophthalmos has been induced in carp by injecting thyrotropin releasing hormone (TRH) (PYRO-glutamyl-histidyl-prolinamide) into the coelom. This effect was dose-dependent (dose range 5-750 mug). It was significantly potentiated by prior administration of beta-1 minus 24 coricotropin (Synacthen, Ciba) and inhibited by prednisclone. No significant increase was obtained with 2-phenylalanine-8-lysire-vasopressin (Octapressin, Sandoz). The results show that in the fish model, TRH exerts an exophthalmogenic effect by stimulating endogenous TSH, whereas in man this is not the case. They afford further evidence that the carp model does not reproduce the conditions which occur in ophthalmic Graves' disease.", "contents": "[Exophthalmogenic effect of thyrotropin releasing hormone (TRH) in the animal experiment]. Exophthalmos has been induced in carp by injecting thyrotropin releasing hormone (TRH) (PYRO-glutamyl-histidyl-prolinamide) into the coelom. This effect was dose-dependent (dose range 5-750 mug). It was significantly potentiated by prior administration of beta-1 minus 24 coricotropin (Synacthen, Ciba) and inhibited by prednisclone. No significant increase was obtained with 2-phenylalanine-8-lysire-vasopressin (Octapressin, Sandoz). The results show that in the fish model, TRH exerts an exophthalmogenic effect by stimulating endogenous TSH, whereas in man this is not the case. They afford further evidence that the carp model does not reproduce the conditions which occur in ophthalmic Graves' disease."} {"id": "PMID:168635", "title": "[Osteomalacia and antiepileptic drugs: study on the pathogenesis].", "content": "Severe osteomalacia with secondary hyperparathyroidism was observed in a 19-year-old mentally retarded girl, who had been treated for several years with antiepileptic drugs. Vitamin D3 orally administered in low doses led to complete reversal of all symptoms and normalization of blood chemistry, X-ray pictures demonstrated healing of all lesions. It is suggested that the alterations of vitamin-D metabolism occuring during the administration of phenobarbital and hydantion are of importance only in patients with an already lowered intake of vitamin D3 or reduced exposure to ultraviolet rays.", "contents": "[Osteomalacia and antiepileptic drugs: study on the pathogenesis]. Severe osteomalacia with secondary hyperparathyroidism was observed in a 19-year-old mentally retarded girl, who had been treated for several years with antiepileptic drugs. Vitamin D3 orally administered in low doses led to complete reversal of all symptoms and normalization of blood chemistry, X-ray pictures demonstrated healing of all lesions. It is suggested that the alterations of vitamin-D metabolism occuring during the administration of phenobarbital and hydantion are of importance only in patients with an already lowered intake of vitamin D3 or reduced exposure to ultraviolet rays."} {"id": "PMID:168636", "title": "[Clinical problems of amebiasis].", "content": "Dagnostic and therapeutic problems of amebiaiss, a disease rarely observed in this country, are discussed in the light of four own cases representing the various courses of the disease. These observations prompt the following conclusions: 1. Amebiasis should be considered in cases of unclear acute or chronic intestinal disease, even if the patient has never visited endemic regions. 2. Non-tropical forms of amebiasis may follow a severe course with complications such as liver abscess or ameboma. 3. The advice of a specialized laboratory is necessary for stool examinations on amebae. 4. Stool examinations for amebiasis should be combined with serological tests. The immunofluorescense test is of special value. False negative results are however possible, especially in cases without tissue inflitration where the infection is limited to the intestinal lumen. 5. Metronidazol (Flagyl) greatly simplifies the treatment of amebiasis as it is both efffective and better tolerated than most other antiamebic agents.", "contents": "[Clinical problems of amebiasis]. Dagnostic and therapeutic problems of amebiaiss, a disease rarely observed in this country, are discussed in the light of four own cases representing the various courses of the disease. These observations prompt the following conclusions: 1. Amebiasis should be considered in cases of unclear acute or chronic intestinal disease, even if the patient has never visited endemic regions. 2. Non-tropical forms of amebiasis may follow a severe course with complications such as liver abscess or ameboma. 3. The advice of a specialized laboratory is necessary for stool examinations on amebae. 4. Stool examinations for amebiasis should be combined with serological tests. The immunofluorescense test is of special value. False negative results are however possible, especially in cases without tissue inflitration where the infection is limited to the intestinal lumen. 5. Metronidazol (Flagyl) greatly simplifies the treatment of amebiasis as it is both efffective and better tolerated than most other antiamebic agents."} {"id": "PMID:168637", "title": "[Anti-lipoprotein autoantibodies with hypolipidemia in infectious rheumatism].", "content": "Presence of anti-lipoprotein activity, a new serological finding in inflammatory rheumatoid disease, has been established in sera and synovial fluids of 20 patients, among which were 6 cases of ankylosing spondylitis. In 18 of the patients, sera were negative for rheumatoid factor. Anti-lipoprotein activity can best be demonstrated by the hemagglutination technique. The binding activity is directed against autologous as well as homologous, however not against heterologous HDL and LDL. It has no specificity for Ag factors. Anti-LDL activity can also be demonstrated by means of double-diffusion tests, whereas no agar-precipitation has been noticeable using HDL as the antigen. Lipoprotein binding-activities were shown to be localized in the Fab fragments of IgG and, in 2 of the cases, also in IgA. We therefore assume that the underlying mechanism of the antilipoprotein activity is auto-immunization, despite of the fact that neither activation of complement nor a stoichiometric character of the binding reaction could be ascertained. Because hemagglutination and immunoprecipitation tests, respectively, were postive with apo-HDL und apo-LDL too, we consider the apo-protein to carry the antigenic site of the reaction. Sera with anti-lipoprotein autoantibodies from patients with chronic rheumatoid disease also presented another pecularity, i.e., a significant decrease of total lipids, cholesterol, and other components of the lipid spectrum. In patients with paraproteinemia, a similar combination of lipoprotein-binding activity and hypolipidemia or hypocholesterolemia was discussed in a previous paper. Regarding the pathogenesis of hypolipidemia or hypocholesterolemia in our patients with rheumatoid disorders, results of LDL turnover studies were indicative for an increase of the lipoprotein catabolism in the presence of anti-lipoprotein autoantibodies, together with a shift of the intra-extravascular distribution toward the intravascular pool. We assume the increased lipoprotein catabolism in these cases to be due to a trapping of lipoproteins by autoantibodies, and to accelerated degradation of these immune complexes. From a practical point of view, it may be of clinical importance that this new serological finding has been observed mainly in patients with chronic rheumatoid disease lacking a rheumatoid serum factor, and was frequently found in patients with ankylosing spondylitis (6 out of the 20 cases). As a screening method, we recommend systematic determinations of the total lipids and of serum cholesterol in all patients with inflammatory rheumatoid disease. In cases with low levels of total lipids and cholesterol, respectively, it may be useful to search for anti-lipoprotein autoantibodies using the hemagglutination method. Results are reported from some preliminary experiments on animals elicitation of an arthritis by means of intra-articular injections of autologous apo-HDL and apo-LDL, and demonstration of autoantibodies against HDL and LDL).", "contents": "[Anti-lipoprotein autoantibodies with hypolipidemia in infectious rheumatism]. Presence of anti-lipoprotein activity, a new serological finding in inflammatory rheumatoid disease, has been established in sera and synovial fluids of 20 patients, among which were 6 cases of ankylosing spondylitis. In 18 of the patients, sera were negative for rheumatoid factor. Anti-lipoprotein activity can best be demonstrated by the hemagglutination technique. The binding activity is directed against autologous as well as homologous, however not against heterologous HDL and LDL. It has no specificity for Ag factors. Anti-LDL activity can also be demonstrated by means of double-diffusion tests, whereas no agar-precipitation has been noticeable using HDL as the antigen. Lipoprotein binding-activities were shown to be localized in the Fab fragments of IgG and, in 2 of the cases, also in IgA. We therefore assume that the underlying mechanism of the antilipoprotein activity is auto-immunization, despite of the fact that neither activation of complement nor a stoichiometric character of the binding reaction could be ascertained. Because hemagglutination and immunoprecipitation tests, respectively, were postive with apo-HDL und apo-LDL too, we consider the apo-protein to carry the antigenic site of the reaction. Sera with anti-lipoprotein autoantibodies from patients with chronic rheumatoid disease also presented another pecularity, i.e., a significant decrease of total lipids, cholesterol, and other components of the lipid spectrum. In patients with paraproteinemia, a similar combination of lipoprotein-binding activity and hypolipidemia or hypocholesterolemia was discussed in a previous paper. Regarding the pathogenesis of hypolipidemia or hypocholesterolemia in our patients with rheumatoid disorders, results of LDL turnover studies were indicative for an increase of the lipoprotein catabolism in the presence of anti-lipoprotein autoantibodies, together with a shift of the intra-extravascular distribution toward the intravascular pool. We assume the increased lipoprotein catabolism in these cases to be due to a trapping of lipoproteins by autoantibodies, and to accelerated degradation of these immune complexes. From a practical point of view, it may be of clinical importance that this new serological finding has been observed mainly in patients with chronic rheumatoid disease lacking a rheumatoid serum factor, and was frequently found in patients with ankylosing spondylitis (6 out of the 20 cases). As a screening method, we recommend systematic determinations of the total lipids and of serum cholesterol in all patients with inflammatory rheumatoid disease. In cases with low levels of total lipids and cholesterol, respectively, it may be useful to search for anti-lipoprotein autoantibodies using the hemagglutination method. Results are reported from some preliminary experiments on animals elicitation of an arthritis by means of intra-articular injections of autologous apo-HDL and apo-LDL, and demonstration of autoantibodies against HDL and LDL)."} {"id": "PMID:168638", "title": "Mouse mammary tumors: alteration of incidence as apparent function of stress.", "content": "Eighty to 100 percent of female mice of the C3H/He strain carrying the Bittner oncogenic virus usually develop mammary tumors within 8 to 18 months after birth when studied under the usual housing and experimental conditions. By subjecting various groups of such mice to environmental circumstances providing different degrees of chronic stress, mammary tumor incidence at 400 days was modified, with incidences ranging from 92 percent under stress to 7 percent in a protected environment. The data suggest that moderate chronic or intermittent stress may predispose such mice to an increased risk of mammary carcinoma, possibly through a resultant compromise of their immunological competence or tumor surveillance system, and that adequate protection from physiological stress may reduce mammary tumor occurrence in mice.", "contents": "Mouse mammary tumors: alteration of incidence as apparent function of stress. Eighty to 100 percent of female mice of the C3H/He strain carrying the Bittner oncogenic virus usually develop mammary tumors within 8 to 18 months after birth when studied under the usual housing and experimental conditions. By subjecting various groups of such mice to environmental circumstances providing different degrees of chronic stress, mammary tumor incidence at 400 days was modified, with incidences ranging from 92 percent under stress to 7 percent in a protected environment. The data suggest that moderate chronic or intermittent stress may predispose such mice to an increased risk of mammary carcinoma, possibly through a resultant compromise of their immunological competence or tumor surveillance system, and that adequate protection from physiological stress may reduce mammary tumor occurrence in mice."} {"id": "PMID:168639", "title": "Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling.", "content": "Compressive forces of physiological magnitude (60 grams per square centimeter) reduce the adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate content of the epiphyses of tibiae from 16-day-old chick embryos. An equivalent hydrostatic pressure applied directly to cells isolated from this tissue also affects cyclic nucleotide accumulation. The tissue response is uniform throughout the epiphysis, whereas the cell response varies according to the area of origin.", "contents": "Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling. Compressive forces of physiological magnitude (60 grams per square centimeter) reduce the adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate content of the epiphyses of tibiae from 16-day-old chick embryos. An equivalent hydrostatic pressure applied directly to cells isolated from this tissue also affects cyclic nucleotide accumulation. The tissue response is uniform throughout the epiphysis, whereas the cell response varies according to the area of origin."} {"id": "PMID:168640", "title": "Predicting response to endocrine therapy in human breast cancer: a hypothesis.", "content": "We hypothesize that the presence of progesterone receptors in human breast tumors may be a sensitive marker for predicting response to endocrine therapy. Progesterone receptors were found in 56 percent of tumors with estrogen receptors, but were absent in tumors without estrogen receptors. Preliminary clinical correlations show that only those breast tumors with progesterone receptors regressed after endocrine therapy.", "contents": "Predicting response to endocrine therapy in human breast cancer: a hypothesis. We hypothesize that the presence of progesterone receptors in human breast tumors may be a sensitive marker for predicting response to endocrine therapy. Progesterone receptors were found in 56 percent of tumors with estrogen receptors, but were absent in tumors without estrogen receptors. Preliminary clinical correlations show that only those breast tumors with progesterone receptors regressed after endocrine therapy."} {"id": "PMID:168641", "title": "Acetaldehyde oxidation by hepatic mitochondria: decrease after chronic ethanol consumption.", "content": "Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde. This is associated with decreased mitochondrial respiration with acetaldehyde as substrate. The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury.", "contents": "Acetaldehyde oxidation by hepatic mitochondria: decrease after chronic ethanol consumption. Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde. This is associated with decreased mitochondrial respiration with acetaldehyde as substrate. The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury."} {"id": "PMID:168643", "title": "Mixed tumor of female breast of unusual duration and size.", "content": "A 72-year-old black woman presented with huge enlargement of the right breast beginning approximately 30 years earlier and progressively enlarging over the years. The breast was stony hard, painless, and inconvenient only because of size and weight. Simple mastectomy was done and pathologic examination showed a benign mixed tumor with large areas of pseudocartilage, osteoid, and bone formation. Preoperatively the serum calcium was 11.0 mg/100 ml and alkaline phosphatase, 550 mU/ml (SMA-12). Postoperative course was uneventful and within several weeks the alkaline phosphatase fell to a normal range (35-115 mU/ml). The case presented requires little comment other than its unusual nature and duration. Extensive bone formation was undoubtedly responsible for the elevated alkaline phosphatase and, as expected, it returned to normal limits following excision of the tumor. Simple mastectomy is considered the treatment of choice.", "contents": "Mixed tumor of female breast of unusual duration and size. A 72-year-old black woman presented with huge enlargement of the right breast beginning approximately 30 years earlier and progressively enlarging over the years. The breast was stony hard, painless, and inconvenient only because of size and weight. Simple mastectomy was done and pathologic examination showed a benign mixed tumor with large areas of pseudocartilage, osteoid, and bone formation. Preoperatively the serum calcium was 11.0 mg/100 ml and alkaline phosphatase, 550 mU/ml (SMA-12). Postoperative course was uneventful and within several weeks the alkaline phosphatase fell to a normal range (35-115 mU/ml). The case presented requires little comment other than its unusual nature and duration. Extensive bone formation was undoubtedly responsible for the elevated alkaline phosphatase and, as expected, it returned to normal limits following excision of the tumor. Simple mastectomy is considered the treatment of choice."} {"id": "PMID:168644", "title": "Osteoporosis, oestrogens and o\u00f6phorectomy. A proposed new test of oestrogenic potency.", "content": "The role of oestrogens, endogenous and exogenous, in the pathogenesis of osteoporis is briefly reviewed. Aspects of research into effects of oestrogens on plasma calcium and phosphorus metabolism, conducted at Groote Schuur Hospital, are incorporated in the discussion. The current role of oestrogen therapy in the prevention of osteoporosis is presented. Evidence suggests that different oestrogenic substances produce different metabolic effects. On this basis a new test for assessment of oestrogenic potency is proposed. It is concluded that appropriate or specific oestrogens are of value in the prevention of osteoporosis, but play little or no role once the process is fully developed. A positive preventive measure recommended is conservatism with regard to ovaries during gynaecological operation on young women.", "contents": "Osteoporosis, oestrogens and o\u00f6phorectomy. A proposed new test of oestrogenic potency. The role of oestrogens, endogenous and exogenous, in the pathogenesis of osteoporis is briefly reviewed. Aspects of research into effects of oestrogens on plasma calcium and phosphorus metabolism, conducted at Groote Schuur Hospital, are incorporated in the discussion. The current role of oestrogen therapy in the prevention of osteoporosis is presented. Evidence suggests that different oestrogenic substances produce different metabolic effects. On this basis a new test for assessment of oestrogenic potency is proposed. It is concluded that appropriate or specific oestrogens are of value in the prevention of osteoporosis, but play little or no role once the process is fully developed. A positive preventive measure recommended is conservatism with regard to ovaries during gynaecological operation on young women."} {"id": "PMID:168645", "title": "Effect of conjugated oestrogen therapy on circulating luteinising hormone in oophorectomised women.", "content": "In a double-blind cross-over study, conjugated equine oestrogen (Premarin) was shown to depress the raised luteinising hormone concentration found in the plasma of oophorectomised women. A dose of 1,25 mg was as effective as 2,5 mg per day.", "contents": "Effect of conjugated oestrogen therapy on circulating luteinising hormone in oophorectomised women. In a double-blind cross-over study, conjugated equine oestrogen (Premarin) was shown to depress the raised luteinising hormone concentration found in the plasma of oophorectomised women. A dose of 1,25 mg was as effective as 2,5 mg per day."} {"id": "PMID:168646", "title": "Sclerosing haemangioma of the lung. A case report.", "content": "A case of pulmonary sclerosing haemangioma composed of blood-filled cavernous spaces separated by septa containing sheets of uniform, epithelioid-type cells and numerous mast cells is described. Although the histogenesis has not been conclusively established, the appearances in this case favour a primary vascular lesion. The variable histological patterns observed in this tumour may cause problems in diagnosis; the differentiation from haemangioma, haemangiopericytoma, pulmonary chemodectoma and benign clear cell tumour of the lung is discussed.", "contents": "Sclerosing haemangioma of the lung. A case report. A case of pulmonary sclerosing haemangioma composed of blood-filled cavernous spaces separated by septa containing sheets of uniform, epithelioid-type cells and numerous mast cells is described. Although the histogenesis has not been conclusively established, the appearances in this case favour a primary vascular lesion. The variable histological patterns observed in this tumour may cause problems in diagnosis; the differentiation from haemangioma, haemangiopericytoma, pulmonary chemodectoma and benign clear cell tumour of the lung is discussed."} {"id": "PMID:168647", "title": "Focal dermal hypoplasia syndrome.", "content": "A patient with focal dermal hypoplasia syndrome is presented. In addition to the usual skin lesions, this patient showed two interesting features, viz. spontaneous involution of the papillomatous lesions on the lips, and osteopathic striae.", "contents": "Focal dermal hypoplasia syndrome. A patient with focal dermal hypoplasia syndrome is presented. In addition to the usual skin lesions, this patient showed two interesting features, viz. spontaneous involution of the papillomatous lesions on the lips, and osteopathic striae."} {"id": "PMID:168648", "title": "Sporadic ulcero-osteolytic neuropathy in Blacks. A report of two cases.", "content": "The triad of a peripheral neuropathy, skin ulceration and destruction of bones and joints of the feet is called ulcero-osteolytic neuropathy, when other common causes of similar lesions have been excluded. Malnutrition, alcoholism and local trauma predispose to the development of the condition. It is to be differentiated from burnt-out leprosy, and is a chronic condition that eventually leads to characteristic deformities.", "contents": "Sporadic ulcero-osteolytic neuropathy in Blacks. A report of two cases. The triad of a peripheral neuropathy, skin ulceration and destruction of bones and joints of the feet is called ulcero-osteolytic neuropathy, when other common causes of similar lesions have been excluded. Malnutrition, alcoholism and local trauma predispose to the development of the condition. It is to be differentiated from burnt-out leprosy, and is a chronic condition that eventually leads to characteristic deformities."} {"id": "PMID:168650", "title": "Colestipol, clofibrate, cholestyramine and combination therapy in the treatment of familial hyperbetalipoproteinaemia.", "content": "Fifty-seven patients, mean age 26 years, suffering from familial hyperbetalipoproteinaemia (Fredrickson type lla and llb), were treated on a low cholesterol, modified polyunsaturated fat diet for a period of 6-12 weeks prior to the introduction of drug therapy. No significant reduction in the serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol or triglyceride was found. Fifty patients were then treated with colestipol for 6 weeks; total and LDL cholesterol decreased by 23%, but triglyceride levels were unaffected. During the following 6 weeks, placebo was administered, and total and LDL cholesterol returned to pretreatment levels. The patients were then randomly allocated into two groups of 16. The first group continued with clofibrate therapy, while the second group received cholestyramine. In the clofibrate group a reduction in total and LDL cholesterol of the order of 17% was noted, similar to cholestethat achieved in this group on colestipol. Triglyceride levels were 15% lower on clofibrate therapy than on colestipol. In the cholestyramine group, there was a 25% decrease in total and LDL cholesterol, compared with pretreatment levels. This reduction was similar to that found when colestipol was administered. Triglyceride values were significantly raised during cholestyramine therapy. Thirteen patients were then subjected to a 6-week period of combination therapy, either clofibrate or colestipol, or clofibrate and cholestyramine. Total and LDL cholesterol were reduced by 32% on combination therapy compared with 18% on colestipol and 23% on either clofibrate or cholestyramine alone. Furthermore, on combined therapy, triglyceride concentrations fell by 20% when compared with the levels found when colestipol, clofibrate or cholestyramine were administered on their own.", "contents": "Colestipol, clofibrate, cholestyramine and combination therapy in the treatment of familial hyperbetalipoproteinaemia. Fifty-seven patients, mean age 26 years, suffering from familial hyperbetalipoproteinaemia (Fredrickson type lla and llb), were treated on a low cholesterol, modified polyunsaturated fat diet for a period of 6-12 weeks prior to the introduction of drug therapy. No significant reduction in the serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol or triglyceride was found. Fifty patients were then treated with colestipol for 6 weeks; total and LDL cholesterol decreased by 23%, but triglyceride levels were unaffected. During the following 6 weeks, placebo was administered, and total and LDL cholesterol returned to pretreatment levels. The patients were then randomly allocated into two groups of 16. The first group continued with clofibrate therapy, while the second group received cholestyramine. In the clofibrate group a reduction in total and LDL cholesterol of the order of 17% was noted, similar to cholestethat achieved in this group on colestipol. Triglyceride levels were 15% lower on clofibrate therapy than on colestipol. In the cholestyramine group, there was a 25% decrease in total and LDL cholesterol, compared with pretreatment levels. This reduction was similar to that found when colestipol was administered. Triglyceride values were significantly raised during cholestyramine therapy. Thirteen patients were then subjected to a 6-week period of combination therapy, either clofibrate or colestipol, or clofibrate and cholestyramine. Total and LDL cholesterol were reduced by 32% on combination therapy compared with 18% on colestipol and 23% on either clofibrate or cholestyramine alone. Furthermore, on combined therapy, triglyceride concentrations fell by 20% when compared with the levels found when colestipol, clofibrate or cholestyramine were administered on their own."} {"id": "PMID:168651", "title": "Pseudogout--CPPD arthropathy, Case reports.", "content": "Pseudogout, or calcium pyrophosphate arthropathy, is a crystalline synovitis, characterised either by acute attacks of joint pain, which usually occur in the large joints, or by a more chronic, progressive form of joint disease. The essential features of the disease are chondrocalcinosis and the presence of pyrophosphate crystals in the synovial fluid. The exact pathogenesis is unknown. Case reports of 2 patients with confiemed pseudogout, and of 1 who is suspected to be suffering from the disease, as well as a summary of the outstanding aspects of the condition, are presented.", "contents": "Pseudogout--CPPD arthropathy, Case reports. Pseudogout, or calcium pyrophosphate arthropathy, is a crystalline synovitis, characterised either by acute attacks of joint pain, which usually occur in the large joints, or by a more chronic, progressive form of joint disease. The essential features of the disease are chondrocalcinosis and the presence of pyrophosphate crystals in the synovial fluid. The exact pathogenesis is unknown. Case reports of 2 patients with confiemed pseudogout, and of 1 who is suspected to be suffering from the disease, as well as a summary of the outstanding aspects of the condition, are presented."} {"id": "PMID:168653", "title": "Lymphography--technique, indications and principles of interpretation.", "content": "The findings in 277 patients investigated by ethiodol lymphography are reviewed, and the applications and limitations of the procedure are presented. The non-specificity of findings is the principal reason for the lack of acceptance of this procedure, and the confusing entity of tuberculous lymphadenitis is discussed.", "contents": "Lymphography--technique, indications and principles of interpretation. The findings in 277 patients investigated by ethiodol lymphography are reviewed, and the applications and limitations of the procedure are presented. The non-specificity of findings is the principal reason for the lack of acceptance of this procedure, and the confusing entity of tuberculous lymphadenitis is discussed."} {"id": "PMID:168655", "title": "Surgical lesions of the ovary in infancy and childhood.", "content": "In 27 years, 64 patients were operated upon for ovarian lesions, 43 for tumors, 12 for nonneoplastic cysts and nine for ovarian torsion. Of all the girls in this age group who were operated upon for appendicitis, 2 percent had ovarian lesions. Of the girls referred for isosexual precocity in the last ten years, 4.7 per cent had ovarian lesions. Of the girls in this age group operated upon for malignant abdominal lesions, excluding hepatic, in the last 15 years, 10.8 per cent had ovarian tumors. Of the 11 tumors with endocrine function, four were malignant. This association is statistically significant. There were no operative deaths. There were no postoperative deaths among six patients with Stage I and II lesions. Mortality was confined to the two patients with Stage III and IV lesions. The surgical approach was designed to conserve ovarian tissue, and adjunctive chemotherapy and radiotherapy were infrequently used.", "contents": "Surgical lesions of the ovary in infancy and childhood. In 27 years, 64 patients were operated upon for ovarian lesions, 43 for tumors, 12 for nonneoplastic cysts and nine for ovarian torsion. Of all the girls in this age group who were operated upon for appendicitis, 2 percent had ovarian lesions. Of the girls referred for isosexual precocity in the last ten years, 4.7 per cent had ovarian lesions. Of the girls in this age group operated upon for malignant abdominal lesions, excluding hepatic, in the last 15 years, 10.8 per cent had ovarian tumors. Of the 11 tumors with endocrine function, four were malignant. This association is statistically significant. There were no operative deaths. There were no postoperative deaths among six patients with Stage I and II lesions. Mortality was confined to the two patients with Stage III and IV lesions. The surgical approach was designed to conserve ovarian tissue, and adjunctive chemotherapy and radiotherapy were infrequently used."} {"id": "PMID:168656", "title": "Effects of exogenous cyclic adenosine monophosphate in hemorrhagic shock.", "content": "Hemorrhageic shock produces potentially damaging alterations in the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP), which is an intracellular second messenger for many hormones. The hypothesis that the administration of exogenous cAMP might have salutary effects on cardiovascular hemodynamics in shock was tested in canine experimetns. Intravenous bolus injection of dibutyryl cAMP (2 mg. per kilogram) produced hyperglycemia, but no changes occurred in heart rate, arerial pressure cardiac output, or in the first derivative of left ventricualr pressure (dp/dt). The findings were similar in conscious and anesthetized (Nembutal) normotensive dogs, in dogs after 3 hours of shock (at blood pressure of 40 mm. Hg) and after the reinfusion of shed blood. The only hemodynamic change noted was a transient hypotensionupon injection of massive doses of dibutyryl-(db-) cAMP or cAMP (greater than 10 mg. per kilogram). The implication of these findings in light of earlier reported hemodynamic effects of cAMP is discussed.", "contents": "Effects of exogenous cyclic adenosine monophosphate in hemorrhagic shock. Hemorrhageic shock produces potentially damaging alterations in the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP), which is an intracellular second messenger for many hormones. The hypothesis that the administration of exogenous cAMP might have salutary effects on cardiovascular hemodynamics in shock was tested in canine experimetns. Intravenous bolus injection of dibutyryl cAMP (2 mg. per kilogram) produced hyperglycemia, but no changes occurred in heart rate, arerial pressure cardiac output, or in the first derivative of left ventricualr pressure (dp/dt). The findings were similar in conscious and anesthetized (Nembutal) normotensive dogs, in dogs after 3 hours of shock (at blood pressure of 40 mm. Hg) and after the reinfusion of shed blood. The only hemodynamic change noted was a transient hypotensionupon injection of massive doses of dibutyryl-(db-) cAMP or cAMP (greater than 10 mg. per kilogram). The implication of these findings in light of earlier reported hemodynamic effects of cAMP is discussed."} {"id": "PMID:168657", "title": "Prognosis of mammary carcinoma in young women.", "content": "One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.", "contents": "Prognosis of mammary carcinoma in young women. One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts."} {"id": "PMID:168661", "title": "The community of human malformation syndromes that shares ectodermal dysplasia and deformities of the hands and feet.", "content": "Syndromes of human congenital malformation may be classified be recognizing communities of syndromes that share multiple phenotypic similarities involving their principal diagnostic features. A community of syndromes that shares various expressions of ectodermal dysplasia and various deformities of the hands and feet is proposed; these syndromes are divisible into two classes according to the presence or absence of anomalies in the nasal or labial regions of the face. The dysmorphogenetic validity of the division is supported by the fact that the syndromes without nasal or labial anomalies have a high frequency of sensorineural deafness as one expression of ectodermal dysplasia whereas those without such anomalies do not. The usefulness of such a syndromal community as a base for evolving a taxonomic scheme of dysmorphogenetic relatedness amongst different syndromes is illustrated.", "contents": "The community of human malformation syndromes that shares ectodermal dysplasia and deformities of the hands and feet. Syndromes of human congenital malformation may be classified be recognizing communities of syndromes that share multiple phenotypic similarities involving their principal diagnostic features. A community of syndromes that shares various expressions of ectodermal dysplasia and various deformities of the hands and feet is proposed; these syndromes are divisible into two classes according to the presence or absence of anomalies in the nasal or labial regions of the face. The dysmorphogenetic validity of the division is supported by the fact that the syndromes without nasal or labial anomalies have a high frequency of sensorineural deafness as one expression of ectodermal dysplasia whereas those without such anomalies do not. The usefulness of such a syndromal community as a base for evolving a taxonomic scheme of dysmorphogenetic relatedness amongst different syndromes is illustrated."} {"id": "PMID:168663", "title": "[An atypical case of Aujeszky's disease in a dog (author's transl)].", "content": "Two cases of Aujeszky's disease in a cat and a dog belonging to the same owner are reported. The two animals each were five months of age. The symptoms shown by the cat were typical of Aujeszky's disease: intense itching, salivation and the head bent to one side. The main symptoms shown by the dog consisted in salivation, ptosis of one eye, a drooping ear, the head bent to one side and ataxia. As itching was not observed in the dog and the animal had spent the first months of its life in wooded surroundings, it could also have been affected with rabies, although it had been inoculated with LEP-Flury vaccine forty days prior to importation. It is of importance to the practitioner to know that itching may be absent in dogs with Aujeszky's disease and that rabies should also be suspected in these cases. Only a laboratory diagnosis will be conclusive. Studies were negative for rabies, the virus of Aujeszky's disease being found to be present in the two cases. The source of infection probably consisted in contaminated pork offal (larynges).", "contents": "[An atypical case of Aujeszky's disease in a dog (author's transl)]. Two cases of Aujeszky's disease in a cat and a dog belonging to the same owner are reported. The two animals each were five months of age. The symptoms shown by the cat were typical of Aujeszky's disease: intense itching, salivation and the head bent to one side. The main symptoms shown by the dog consisted in salivation, ptosis of one eye, a drooping ear, the head bent to one side and ataxia. As itching was not observed in the dog and the animal had spent the first months of its life in wooded surroundings, it could also have been affected with rabies, although it had been inoculated with LEP-Flury vaccine forty days prior to importation. It is of importance to the practitioner to know that itching may be absent in dogs with Aujeszky's disease and that rabies should also be suspected in these cases. Only a laboratory diagnosis will be conclusive. Studies were negative for rabies, the virus of Aujeszky's disease being found to be present in the two cases. The source of infection probably consisted in contaminated pork offal (larynges)."} {"id": "PMID:168664", "title": "[I.B.R (author's transl)].", "content": "The clinical pictures which may be produced by IBR/IPV virus in cattle are briefly reviewed. Up to the autumn of 1972, infection occurred only sporadically in the Netherlands, no typical cases of IBR having been reported up to the fall of that year. Since the winter of 1972-1973 IBR has increasingly been diagnosed, particularly during the winter months. It may, however, be mistaken for other infections of the respiratory tract. The infection apears to be spreading. The clinical features, diagnosis, epizootiology and methods of treatment are discussed. Administration of a vaccine may be indicated in some herds where IBR-virus is present or its introduction is to be expected. In that case, inoculation of a monospecific vaccine, directed against IBR virus only is to be preferred to the use of combination vaccines.", "contents": "[I.B.R (author's transl)]. The clinical pictures which may be produced by IBR/IPV virus in cattle are briefly reviewed. Up to the autumn of 1972, infection occurred only sporadically in the Netherlands, no typical cases of IBR having been reported up to the fall of that year. Since the winter of 1972-1973 IBR has increasingly been diagnosed, particularly during the winter months. It may, however, be mistaken for other infections of the respiratory tract. The infection apears to be spreading. The clinical features, diagnosis, epizootiology and methods of treatment are discussed. Administration of a vaccine may be indicated in some herds where IBR-virus is present or its introduction is to be expected. In that case, inoculation of a monospecific vaccine, directed against IBR virus only is to be preferred to the use of combination vaccines."} {"id": "PMID:168665", "title": "Electroencephalographic study of an infant with phosphoribosylpyrophosphate synthetase deficiency.", "content": "In a hypouricemic and mentally retarded infant due to a defect of 5-phosphoribosylpyrophosphate synthetase, electroencephalograms were recorded at the age of 4, 7, 10 and 11 months. Hypsarrhythmia was first observed at the age of 10 months, and markedly improved after ACTH therapy with concomitant increase in the enzyme activity of erythrocytes.", "contents": "Electroencephalographic study of an infant with phosphoribosylpyrophosphate synthetase deficiency. In a hypouricemic and mentally retarded infant due to a defect of 5-phosphoribosylpyrophosphate synthetase, electroencephalograms were recorded at the age of 4, 7, 10 and 11 months. Hypsarrhythmia was first observed at the age of 10 months, and markedly improved after ACTH therapy with concomitant increase in the enzyme activity of erythrocytes."} {"id": "PMID:168666", "title": "Reticuloendothelial system function test using 131I-labeled aggregated albumin.", "content": "The reticuloendothelial system function test using 131I-labeled aggregated human albumin (131IAA) as test particle is thought to be one of the best methods for the study of RES function of human beings. This method needs a large amount of 131IAA, but 131IAA has been used as a tracer of liver scintiscanning, and we tired to study RES function by using commercially available 131IAA specially made as tracer of liver scintiscanning. Because the amount of 131IAA used in this study was smaller than the critical dosis, our interest was focussed on the catabolic activity of 131IAA phagocytized by Kupffer's cells. The plasma obtained 60 min after 131IAA injection was fractionated into two distinct peaks by gel column chromatography; ionic 131I and protein-bound 131IAA. The ratio between ionic 131I and bound 131IAA (F/B ratio) was studied in various diseases. The F/B ratios of liver cirrhosis and hepatoma were significantly lower than that of the control. The lowered F/B ratio had no correlation with other liver function tests, data of hepatic scintiscanning, or with clinical findings. The F/B ratio was also not correlated with congo red index as RES function test.", "contents": "Reticuloendothelial system function test using 131I-labeled aggregated albumin. The reticuloendothelial system function test using 131I-labeled aggregated human albumin (131IAA) as test particle is thought to be one of the best methods for the study of RES function of human beings. This method needs a large amount of 131IAA, but 131IAA has been used as a tracer of liver scintiscanning, and we tired to study RES function by using commercially available 131IAA specially made as tracer of liver scintiscanning. Because the amount of 131IAA used in this study was smaller than the critical dosis, our interest was focussed on the catabolic activity of 131IAA phagocytized by Kupffer's cells. The plasma obtained 60 min after 131IAA injection was fractionated into two distinct peaks by gel column chromatography; ionic 131I and protein-bound 131IAA. The ratio between ionic 131I and bound 131IAA (F/B ratio) was studied in various diseases. The F/B ratios of liver cirrhosis and hepatoma were significantly lower than that of the control. The lowered F/B ratio had no correlation with other liver function tests, data of hepatic scintiscanning, or with clinical findings. The F/B ratio was also not correlated with congo red index as RES function test."} {"id": "PMID:168668", "title": "Assessment of the teratogenic potential of surfactants. Part III--dermal application of LAS and soap.", "content": "The surfactant linear alkylbenzene sulphonate (LAS) was examined for embryotoxic and teratogenic potential following percutaneous administration. Solutions containing, 0.03, 0.3 and 3% LAS were applied to shaved skin during pregnancy days 2-13 in mice, 2-15 in rats and 1-16 in rabbits. Dosages employed were 0.5 ml/rat or mouse/day and 10 ml/rabbit/day. For comparison further groups of rats and mice were similarly treated with concentrations of 0.3, 3 and 30% of a standard soap solution. Marked maternal toxicity in the form of local skin reaction, irritability, weight loss and failure to maintain or establish pregnancy was evident in mice treated with LAS 3% or soap, 3 or 30%; marked local reaction and weight loss also occurred in rabbits receiving LAS 3% but the reduction in the number of pregnancies maintained was not significant. Moderate maternal toxicity was observed among mice treated with LAS, 0.3% and mild maternal toxicity in rats receiving LAS 3% or soap 30% and rabbits receiving LAS 0.3%. Effects on litter parameters were generally restricted to dosages causing marked maternal toxicity in mice, the principal effects being higher foetal loss (with consequent reduction in viable litter size) arising from an increased incidence of total litter losses. When dams showing total litter loss were excluded from the calculations, litter parameters were not unduly different from those of controls. Although LAS at 3% was considered to show marked maternal toxicity in the rabbit, the slightly higher foetal loss and lower litter size did not differ significantly from control values.", "contents": "Assessment of the teratogenic potential of surfactants. Part III--dermal application of LAS and soap. The surfactant linear alkylbenzene sulphonate (LAS) was examined for embryotoxic and teratogenic potential following percutaneous administration. Solutions containing, 0.03, 0.3 and 3% LAS were applied to shaved skin during pregnancy days 2-13 in mice, 2-15 in rats and 1-16 in rabbits. Dosages employed were 0.5 ml/rat or mouse/day and 10 ml/rabbit/day. For comparison further groups of rats and mice were similarly treated with concentrations of 0.3, 3 and 30% of a standard soap solution. Marked maternal toxicity in the form of local skin reaction, irritability, weight loss and failure to maintain or establish pregnancy was evident in mice treated with LAS 3% or soap, 3 or 30%; marked local reaction and weight loss also occurred in rabbits receiving LAS 3% but the reduction in the number of pregnancies maintained was not significant. Moderate maternal toxicity was observed among mice treated with LAS, 0.3% and mild maternal toxicity in rats receiving LAS 3% or soap 30% and rabbits receiving LAS 0.3%. Effects on litter parameters were generally restricted to dosages causing marked maternal toxicity in mice, the principal effects being higher foetal loss (with consequent reduction in viable litter size) arising from an increased incidence of total litter losses. When dams showing total litter loss were excluded from the calculations, litter parameters were not unduly different from those of controls. Although LAS at 3% was considered to show marked maternal toxicity in the rabbit, the slightly higher foetal loss and lower litter size did not differ significantly from control values."} {"id": "PMID:168669", "title": "Influence of chronic exposure to cadmium on hepatic and renal cyclic AMP-protein kinase system.", "content": "Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) to rats for 45 days significantly elevated the endogenous levels of cyclic AMP (cAMP) in hepatic tissue. However, the cAMP binding to hepatic protein kinase was decreased following cadmium administration, as was the kinase activity ratio. Although both doses of cadmium produced slight alterations in the cAMP-independent form of hepatic protein kinase, only the 1.0 mg/kg dose significantly depressed (24%) the activity of the cAMP-dependent enzyme. In contrast to liver, chronic exposure to cadmium significantly reduced the endogenous cAMP levels in kidney cortex. Although treatment with the lower dose (0.25 mg/kg) failed to alter either the cAMP-binding capacity of the renal enzyme or the kinase activity ratio, the higher dose (1 mg/kg) of cadmium did cause a significant increase in both parameters. In addition, cadmium treatment produced a significant decrease in both the cAMP-dependent and the independent forms of protein kinase in kidney cortex. Data suggest that the concentration of cAMP as well as its interaction with cAMP-dependent and independent forms of protein kinase, are altered in both kidney and liver following the prolonged exposure to cadmium.", "contents": "Influence of chronic exposure to cadmium on hepatic and renal cyclic AMP-protein kinase system. Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) to rats for 45 days significantly elevated the endogenous levels of cyclic AMP (cAMP) in hepatic tissue. However, the cAMP binding to hepatic protein kinase was decreased following cadmium administration, as was the kinase activity ratio. Although both doses of cadmium produced slight alterations in the cAMP-independent form of hepatic protein kinase, only the 1.0 mg/kg dose significantly depressed (24%) the activity of the cAMP-dependent enzyme. In contrast to liver, chronic exposure to cadmium significantly reduced the endogenous cAMP levels in kidney cortex. Although treatment with the lower dose (0.25 mg/kg) failed to alter either the cAMP-binding capacity of the renal enzyme or the kinase activity ratio, the higher dose (1 mg/kg) of cadmium did cause a significant increase in both parameters. In addition, cadmium treatment produced a significant decrease in both the cAMP-dependent and the independent forms of protein kinase in kidney cortex. Data suggest that the concentration of cAMP as well as its interaction with cAMP-dependent and independent forms of protein kinase, are altered in both kidney and liver following the prolonged exposure to cadmium."} {"id": "PMID:168670", "title": "Teratology studies of a mixture of tallow alkyl ethoxylate and linear alkylbenzene sulfonate in rats and rabbits.", "content": "A mixture of 55% tallow alkyl ethoxylate sulfate (TAE3S) and 45% of linear alkylbenzene sulfonate (LAS) was fed to two generations of rats at dietary levels of 0.1, 0.5 or 1.0%. The rats were fed the surfactant mixture either continuously or during the organogenesis (days 6-15) period of six pregnancies. In addition, pregnant New Zealand rabbits were given 50, 100 or 300 mg/kg doses of the surfactant mixture by intubation on days 2-16 of gestation during a single pregnancy. No adverse effects were noted on conception, fetal viability or post-natal survival in either generation of rats. There were no statistical differences among the groups of rat fetuses taken by Caesarian section and examined for birth defects. Of 1210 rat fetuses, the overall incidence of abnormal young was 9.0%. Similarly, no adverse effects were seen in rabbits treated with the surfactant mixture. Of 855 rabbit fetuses, 5.7% were abnormal, but the incidences of defective fetuses in the test groups were not significantly different from those in controls. Thus, no test related effects were seen on reproduction or embryonic development in either animal species.", "contents": "Teratology studies of a mixture of tallow alkyl ethoxylate and linear alkylbenzene sulfonate in rats and rabbits. A mixture of 55% tallow alkyl ethoxylate sulfate (TAE3S) and 45% of linear alkylbenzene sulfonate (LAS) was fed to two generations of rats at dietary levels of 0.1, 0.5 or 1.0%. The rats were fed the surfactant mixture either continuously or during the organogenesis (days 6-15) period of six pregnancies. In addition, pregnant New Zealand rabbits were given 50, 100 or 300 mg/kg doses of the surfactant mixture by intubation on days 2-16 of gestation during a single pregnancy. No adverse effects were noted on conception, fetal viability or post-natal survival in either generation of rats. There were no statistical differences among the groups of rat fetuses taken by Caesarian section and examined for birth defects. Of 1210 rat fetuses, the overall incidence of abnormal young was 9.0%. Similarly, no adverse effects were seen in rabbits treated with the surfactant mixture. Of 855 rabbit fetuses, 5.7% were abnormal, but the incidences of defective fetuses in the test groups were not significantly different from those in controls. Thus, no test related effects were seen on reproduction or embryonic development in either animal species."} {"id": "PMID:168671", "title": "Relation of the pituitary gland to gonadal hormone effects on the adrenocortical 11beta-hydroxylase system in rats.", "content": "Studies were conducted to further examine the mechanisms responsible for gonadal hormone effects on the rat adrenocortical 11beta-hydroxylase system. Despite higher concentrations of cytochrome P-450 and larger 11-deoxycorticosterone (DOC)-induced difference spectra in adrenal mitochondria from females than males, no sex difference in 11beta-hydroxylase activity was observed. The pregnenolone-induced difference spectrum, indicative of cholesterol binding to cytochrome P-450, also was similar in males and females. Testosterone administration to castrated males lowered both 11beta-hydroxylase activity and mitochondrial cytochrome P-450 content. Estradiol produced the opposite effects in castrated females. However, when given to ACTH-replaced hypophysectomized rats, neither testosterone nor estradiol affected cytochrome P-450 levels or the rate of 11beta-hydroxylation. These observations, taken with the known effects of estradiol and testosterone on ACTH secretion in rats and the effects of ACTH on 11beta-hydroxylation, indicate that gonadal hormone effects on the 11beta-hydroxylase system are mediated by ACTH.", "contents": "Relation of the pituitary gland to gonadal hormone effects on the adrenocortical 11beta-hydroxylase system in rats. Studies were conducted to further examine the mechanisms responsible for gonadal hormone effects on the rat adrenocortical 11beta-hydroxylase system. Despite higher concentrations of cytochrome P-450 and larger 11-deoxycorticosterone (DOC)-induced difference spectra in adrenal mitochondria from females than males, no sex difference in 11beta-hydroxylase activity was observed. The pregnenolone-induced difference spectrum, indicative of cholesterol binding to cytochrome P-450, also was similar in males and females. Testosterone administration to castrated males lowered both 11beta-hydroxylase activity and mitochondrial cytochrome P-450 content. Estradiol produced the opposite effects in castrated females. However, when given to ACTH-replaced hypophysectomized rats, neither testosterone nor estradiol affected cytochrome P-450 levels or the rate of 11beta-hydroxylation. These observations, taken with the known effects of estradiol and testosterone on ACTH secretion in rats and the effects of ACTH on 11beta-hydroxylation, indicate that gonadal hormone effects on the 11beta-hydroxylase system are mediated by ACTH."} {"id": "PMID:168674", "title": "Bile composition and bile cast formation after transplantation of the liver in man.", "content": "Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver.", "contents": "Bile composition and bile cast formation after transplantation of the liver in man. Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver."} {"id": "PMID:168675", "title": "Detection of hepatoma associated embryonic antigen in tumour-bearer serum.", "content": "Embryonic antigen associated with an aminoazo dye-induced rat hepatoma was identified in the serum from rats bearing progressively growing tumours. Antigenic activity in serum samples was detected by their capacity to neutralize multiparous rat serum antibody reacting with surface embryonic antigens expressed upon viable hepatoma cells as assessed with use of the indirect membrane immunofluorescence test. Serum taken at various states of tumour growth from hepatoma-bearing rats was separated by Sephadex G-150 gel filtration column chromatography at pH 7.3 and pH 2.8 with use of procedures designed to identify free circulating antigen and antigen derived from immune complexes. Hepatoma-associated embryonic antigen was demonstrable in tumour-bearer serum in a free form most markedly in the later stages after implantation of tumour cells (from the end of the 2nd week to the 5th week of tumour growth). Antigenic activity in fractions derived from immune complexes was detected earlier during tumour development (from day 8 after tumour induction), and this was present in all serum samples taken up to the 5th week after tumour cell inoculation.", "contents": "Detection of hepatoma associated embryonic antigen in tumour-bearer serum. Embryonic antigen associated with an aminoazo dye-induced rat hepatoma was identified in the serum from rats bearing progressively growing tumours. Antigenic activity in serum samples was detected by their capacity to neutralize multiparous rat serum antibody reacting with surface embryonic antigens expressed upon viable hepatoma cells as assessed with use of the indirect membrane immunofluorescence test. Serum taken at various states of tumour growth from hepatoma-bearing rats was separated by Sephadex G-150 gel filtration column chromatography at pH 7.3 and pH 2.8 with use of procedures designed to identify free circulating antigen and antigen derived from immune complexes. Hepatoma-associated embryonic antigen was demonstrable in tumour-bearer serum in a free form most markedly in the later stages after implantation of tumour cells (from the end of the 2nd week to the 5th week of tumour growth). Antigenic activity in fractions derived from immune complexes was detected earlier during tumour development (from day 8 after tumour induction), and this was present in all serum samples taken up to the 5th week after tumour cell inoculation."} {"id": "PMID:168676", "title": "[Regenerative growth of asvitic hepatoma 22A].", "content": "A study was made of the recurrent growth of ascite hepatoma 22A, occurring at transplantation of 11-12-day old tumours to new hosts. The mitotic activity of the hepatoma was found to increase by 3 to 4 times (12-15 hours after inoculation). This increased cell proliferation is due mainly to a sharp shortening of all the periods of mitotic cycle. During the recurrent growth, the resting R1 cells resume their mitotic cycle. No resumption of the mitotic cycle by the resting R2 cells was observed", "contents": "[Regenerative growth of asvitic hepatoma 22A]. A study was made of the recurrent growth of ascite hepatoma 22A, occurring at transplantation of 11-12-day old tumours to new hosts. The mitotic activity of the hepatoma was found to increase by 3 to 4 times (12-15 hours after inoculation). This increased cell proliferation is due mainly to a sharp shortening of all the periods of mitotic cycle. During the recurrent growth, the resting R1 cells resume their mitotic cycle. No resumption of the mitotic cycle by the resting R2 cells was observed"} {"id": "PMID:168672", "title": "Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 1. animal preparation, instrumentation, and validity of model.", "content": "Reduce nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to the reliable.", "contents": "Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 1. animal preparation, instrumentation, and validity of model. Reduce nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to the reliable."} {"id": "PMID:168673", "title": "Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 2. effects of alterations in arterial carbon dioxide tension, blood pressure, and blood volume.", "content": "The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Paco2. In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.", "contents": "Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 2. effects of alterations in arterial carbon dioxide tension, blood pressure, and blood volume. The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Paco2. In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction."} {"id": "PMID:168678", "title": "[Glomus tumor of arterio-venous anastomoses].", "content": "Collected data of 74 national authors comprising 267 glomus tumors are reported. Based on these data and 49 personal authors' observations the clinic, pathogenesis, pathological anatomy and diagnosis of this rather rare lesion are described. Surgical intervention consisting in total removal of the tumor together with its capsule is the only proper method of treatment for the Barre-Masson disease.", "contents": "[Glomus tumor of arterio-venous anastomoses]. Collected data of 74 national authors comprising 267 glomus tumors are reported. Based on these data and 49 personal authors' observations the clinic, pathogenesis, pathological anatomy and diagnosis of this rather rare lesion are described. Surgical intervention consisting in total removal of the tumor together with its capsule is the only proper method of treatment for the Barre-Masson disease."} {"id": "PMID:168679", "title": "[Serum and liver lipase activity in chickens during the 1st month of life].", "content": "Method according to DIRSTINE (1968) was employed to study the activities of serum and liver lipase in White Leghorn cockerels during early post-incubation ontogenesis; as to serum lipase, two embryo intervals were also studied (the 13th and 20th day of incubation). From the average value of 4.4 ummol (13th day), serum lipase activity increased to the average value of 7.5 ummol (20th day). The first day after hatching the average value was 3.5 ummol which remained almost unchanged until the 9th day, with the exception of a slight drop the third day; an increase of activities was observed on the 13th day (4.9 ummol), 15th day (3.5 ummol), 21st day (7.6 ummol), 22nd day (5.5 ummol), and 24th day (8.8 ummol). The minimum average activity of 2.5 ummol was measured the 32nd day. Liver lipase activity was observed to drop from the first-day starting value of 20.6 ummol to 9.8 ummol (the second day), with a subsequent increase to 14.9 ummol (the 4th day). The maximum values were recorded the 13th day (26.2 ummol) and the 15th day (28.7 ummol) whereas the minimum average value was obtained the 32nd day (6.3 ummol). Liver lipase activity drop on the second day of age and serum lipase activity drop on the third day with subsequent increase are probably associated with the change from yolk-sac nutrition to feeding per os. Some stabilization of serum and liver lipase occurs the 32nd day; the values found in adult fowl were almost the same as the 32nd day values.", "contents": "[Serum and liver lipase activity in chickens during the 1st month of life]. Method according to DIRSTINE (1968) was employed to study the activities of serum and liver lipase in White Leghorn cockerels during early post-incubation ontogenesis; as to serum lipase, two embryo intervals were also studied (the 13th and 20th day of incubation). From the average value of 4.4 ummol (13th day), serum lipase activity increased to the average value of 7.5 ummol (20th day). The first day after hatching the average value was 3.5 ummol which remained almost unchanged until the 9th day, with the exception of a slight drop the third day; an increase of activities was observed on the 13th day (4.9 ummol), 15th day (3.5 ummol), 21st day (7.6 ummol), 22nd day (5.5 ummol), and 24th day (8.8 ummol). The minimum average activity of 2.5 ummol was measured the 32nd day. Liver lipase activity was observed to drop from the first-day starting value of 20.6 ummol to 9.8 ummol (the second day), with a subsequent increase to 14.9 ummol (the 4th day). The maximum values were recorded the 13th day (26.2 ummol) and the 15th day (28.7 ummol) whereas the minimum average value was obtained the 32nd day (6.3 ummol). Liver lipase activity drop on the second day of age and serum lipase activity drop on the third day with subsequent increase are probably associated with the change from yolk-sac nutrition to feeding per os. Some stabilization of serum and liver lipase occurs the 32nd day; the values found in adult fowl were almost the same as the 32nd day values."} {"id": "PMID:168680", "title": "Veterinary aspects of salmonid fish farming: husbandry diseases.", "content": "Most disease problems affecting farmed salmonid fish are either caused or exacerbated by bad husbandry and poor environmental conditions. The aspects of water quality and nutrition which are significant in causing husbandry problems are considered. The clinical aspects of these diseases are decribed in terms of the life cycle of salmonids, and methods of prevention are discussed.", "contents": "Veterinary aspects of salmonid fish farming: husbandry diseases. Most disease problems affecting farmed salmonid fish are either caused or exacerbated by bad husbandry and poor environmental conditions. The aspects of water quality and nutrition which are significant in causing husbandry problems are considered. The clinical aspects of these diseases are decribed in terms of the life cycle of salmonids, and methods of prevention are discussed."} {"id": "PMID:168681", "title": "Trials with Marek's disease vaccines prepared from a turkey herpes virus and an attenuated Marek's disease virus.", "content": "In field trials involving over 224,000 fowls in 11 different commercial flocks, three vaccines were used, namely a freeze-dried vaccine prepared from a turkey herpes virus, a cell-associated virus vaccine prepared from the same isolate and a cell-associated vaccine prepared from a strain of Marek's disease virus isolated from a fowl. The mortality from Marek's disease was reduced by 80 per cent to 95 per cent in birds vaccinated with the freeze-dried vaccine. Cell associated vaccines gave slightly less protection.", "contents": "Trials with Marek's disease vaccines prepared from a turkey herpes virus and an attenuated Marek's disease virus. In field trials involving over 224,000 fowls in 11 different commercial flocks, three vaccines were used, namely a freeze-dried vaccine prepared from a turkey herpes virus, a cell-associated virus vaccine prepared from the same isolate and a cell-associated vaccine prepared from a strain of Marek's disease virus isolated from a fowl. The mortality from Marek's disease was reduced by 80 per cent to 95 per cent in birds vaccinated with the freeze-dried vaccine. Cell associated vaccines gave slightly less protection."} {"id": "PMID:168691", "title": "4-Nitrobenzoic acid reductase of Ascaris lumbricoides var suum. Substrate specificity and reaction products.", "content": "1. The substrate specificity of nitro-reductase from Ascaris lumbricoides varsum was determined. This enzyme reduced nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol. The same enzyme preparation reduced azobenzene, 4-dimethylaminoazobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene. Nitrobenzaldehyde isomers were not reduced to the alcohols. 2. The products of nitro- and azo-reduction were the corresponding amines, no hydroxylamino or hydrazo compounds were detected. 3. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction and neither reaction was inhibited by oxygen. 4. Ammonium sulphate fractionation failed to separate azo- and nitro-reductase activities. The molecular weight of both azo- and nitro-reductase was about 130 000.", "contents": "4-Nitrobenzoic acid reductase of Ascaris lumbricoides var suum. Substrate specificity and reaction products. 1. The substrate specificity of nitro-reductase from Ascaris lumbricoides varsum was determined. This enzyme reduced nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol. The same enzyme preparation reduced azobenzene, 4-dimethylaminoazobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene. Nitrobenzaldehyde isomers were not reduced to the alcohols. 2. The products of nitro- and azo-reduction were the corresponding amines, no hydroxylamino or hydrazo compounds were detected. 3. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction and neither reaction was inhibited by oxygen. 4. Ammonium sulphate fractionation failed to separate azo- and nitro-reductase activities. The molecular weight of both azo- and nitro-reductase was about 130 000."} {"id": "PMID:168693", "title": "[Influence of fenoterol of cAMP levels and motility on the rat uterus in vitro (author's transl)].", "content": "CAMP levels of isolated rat uteri (2nmol/g wwt) were increased by Fenoterol (10(-4)--1 mug/ml) in a dose dependent manner reaching concentrations of more than 10nmol/g withing 2--5 min. AT 2 TIMES 10(-3) MUG/ML Fenoterol inhibited spontaneous contractions of the rat uterus in vitro. A 10,000 fold higher dosis of Fenoterol was needed to elicit a similar degree of inhibition, when contractions were induced by 0.6 mU/ml Oxytocin. However cAMP levels were elevated by Fenoterol in presence of Oxytocin, uterine contractions were not inhibited, i.e. the elevation of cAMP after administration of Fenoterol is correlated with a relaxant effect only in uteri contracting spontaneously.", "contents": "[Influence of fenoterol of cAMP levels and motility on the rat uterus in vitro (author's transl)]. CAMP levels of isolated rat uteri (2nmol/g wwt) were increased by Fenoterol (10(-4)--1 mug/ml) in a dose dependent manner reaching concentrations of more than 10nmol/g withing 2--5 min. AT 2 TIMES 10(-3) MUG/ML Fenoterol inhibited spontaneous contractions of the rat uterus in vitro. A 10,000 fold higher dosis of Fenoterol was needed to elicit a similar degree of inhibition, when contractions were induced by 0.6 mU/ml Oxytocin. However cAMP levels were elevated by Fenoterol in presence of Oxytocin, uterine contractions were not inhibited, i.e. the elevation of cAMP after administration of Fenoterol is correlated with a relaxant effect only in uteri contracting spontaneously."} {"id": "PMID:168694", "title": "[A spectrophotometric method for the determination of serum cholinesterase variants with succinyl choline as substrate (author's transl)].", "content": "A simple and rapid method for the estimation of the hydrolysis of succinyl choline by serum cholinesterase variants is described. Succinyl choline, as substrate for the enzyme assay, has many advantages over other substrates (acetyl choline, benzoyl choline and butyryl choline) which have no clinical application. Choline, the hydrolytic product of succinyl choline, is oxidized to betaine aldehyde by choline oxidase (EC 1.1.99.1), a rat liver mitochondrial preparation; this is coupled to the reduction of cytochrome c which is measured at 550 nm. Fifty normal sera (UU), 17 heterozygous (UA) and 8 atypical (AA) were tested with this method, and on the basis of resistance to dibucaine (Cinchocain; Kalow, W. & Genest, K. (1957) Canad. J. Biochem. Physiol. 35, 339-346) inhibition, three distinct groups could be established using succinyl choline as substrate. These results are comparable with the standard optical method of Kalow & Genest (cf. above) using benzoyl choline as substrate.", "contents": "[A spectrophotometric method for the determination of serum cholinesterase variants with succinyl choline as substrate (author's transl)]. A simple and rapid method for the estimation of the hydrolysis of succinyl choline by serum cholinesterase variants is described. Succinyl choline, as substrate for the enzyme assay, has many advantages over other substrates (acetyl choline, benzoyl choline and butyryl choline) which have no clinical application. Choline, the hydrolytic product of succinyl choline, is oxidized to betaine aldehyde by choline oxidase (EC 1.1.99.1), a rat liver mitochondrial preparation; this is coupled to the reduction of cytochrome c which is measured at 550 nm. Fifty normal sera (UU), 17 heterozygous (UA) and 8 atypical (AA) were tested with this method, and on the basis of resistance to dibucaine (Cinchocain; Kalow, W. & Genest, K. (1957) Canad. J. Biochem. Physiol. 35, 339-346) inhibition, three distinct groups could be established using succinyl choline as substrate. These results are comparable with the standard optical method of Kalow & Genest (cf. above) using benzoyl choline as substrate."} {"id": "PMID:168690", "title": "[Changes in the activity of alkaline phosphatase and the level of thiamine diphosphatase in simulations of B1 avitaminosis].", "content": "Alimentary B1 avitaminosis was attended by a declining activity of alkaline phosphatase in the brain and spleen of rats. A single administration of oxythiamine to rats in a dose of 400 mg/kg produced during the first hours an increased activity of alkaline phosphatase in the liver, brain and, to a lesser extent, in a number of other organs and reduced the thiamine-diphosphate content in the liver, brain and other tissues. The thiamin-diphosphate level in the brain returned back to normal in 12 hours, and in other tissues-towards the 3--5th day. In 24 hours after introduction of oxythiamine the activity of alkaline phosphatase was up in the liver alone, while in the brain the activity of the enzyme decreased. Thiamine, used in a dose of 400 mg/kg, exerted on the activity of alkaline phosphatase in a number of tissues an action similar to that of oxythiamine. It is suggested that the activation of alkaline phosphatase 3--12 hours following adminstration of a large dose of thiamine or oxythiamine is of a non-specific nature. Subcutaneous introduction of a commercial alkaline phosphatase preparation to rats brought down the thiamine-diphosphate level in all of the tissues under investigation. The presumed mechanisms accounting for the fall of thiamine-diphosphate and the possible part played in this process by alkaline phosphatase are discussed.", "contents": "[Changes in the activity of alkaline phosphatase and the level of thiamine diphosphatase in simulations of B1 avitaminosis]. Alimentary B1 avitaminosis was attended by a declining activity of alkaline phosphatase in the brain and spleen of rats. A single administration of oxythiamine to rats in a dose of 400 mg/kg produced during the first hours an increased activity of alkaline phosphatase in the liver, brain and, to a lesser extent, in a number of other organs and reduced the thiamine-diphosphate content in the liver, brain and other tissues. The thiamin-diphosphate level in the brain returned back to normal in 12 hours, and in other tissues-towards the 3--5th day. In 24 hours after introduction of oxythiamine the activity of alkaline phosphatase was up in the liver alone, while in the brain the activity of the enzyme decreased. Thiamine, used in a dose of 400 mg/kg, exerted on the activity of alkaline phosphatase in a number of tissues an action similar to that of oxythiamine. It is suggested that the activation of alkaline phosphatase 3--12 hours following adminstration of a large dose of thiamine or oxythiamine is of a non-specific nature. Subcutaneous introduction of a commercial alkaline phosphatase preparation to rats brought down the thiamine-diphosphate level in all of the tissues under investigation. The presumed mechanisms accounting for the fall of thiamine-diphosphate and the possible part played in this process by alkaline phosphatase are discussed."} {"id": "PMID:168695", "title": "Radioimmunoassay of serum deoxycorticosterone: normal values and changes of serum deoxycorticosterone after adrenal stimulation.", "content": "A sensitive radioimmunoassay for estimating serum deoxycorticosterone is described which involves descending \"overrunning\" paper chromatography. An ethanolic paper eluate is used as a solvent for unlabelled deoxycorticosterone in the preparation of the standard curve. The values of the water blanks (7 ng/l) are similar to the sensitivity of the standard curve (5.8 ng/l). The normal mean serum concentration of deoxycorticosterone was found to be 84 +/- 29 ng/l (n = 30) in males and 55 +/- 31 ng/l (n = 35) in females. Serum deoxycorticosterone rose in healthy subjects upon injection of ACTH, after induction of insulin hypoglycemia and after administration of metyrapone, while the rise was absent or blunted in patients with Addison's disease and in patients with pituitary failure.", "contents": "Radioimmunoassay of serum deoxycorticosterone: normal values and changes of serum deoxycorticosterone after adrenal stimulation. A sensitive radioimmunoassay for estimating serum deoxycorticosterone is described which involves descending \"overrunning\" paper chromatography. An ethanolic paper eluate is used as a solvent for unlabelled deoxycorticosterone in the preparation of the standard curve. The values of the water blanks (7 ng/l) are similar to the sensitivity of the standard curve (5.8 ng/l). The normal mean serum concentration of deoxycorticosterone was found to be 84 +/- 29 ng/l (n = 30) in males and 55 +/- 31 ng/l (n = 35) in females. Serum deoxycorticosterone rose in healthy subjects upon injection of ACTH, after induction of insulin hypoglycemia and after administration of metyrapone, while the rise was absent or blunted in patients with Addison's disease and in patients with pituitary failure."} {"id": "PMID:168696", "title": "[Soft tissue tumours on the back of the knee].", "content": "Soft tissue tumours behind the knee have rarely been described in literature. We have studied 74 patients with 79 tumours and pseudotumours in this area, and made a survey about pathology, clinical features, diagnosis, differentialdiagnosis and operative treatment. We have pointed out the varying nomenclature and confusion in definition ob a bursa and Baker's synovial herniation. The analysis of the casuistry showed predominantly gangliae, bursae and Baker's cysts. We have given special prominence to subfascial lipoma, malignant synovioma and nerve tumours as rare conditiones. Our own cases of synovioma and nerve tumours have been separately described.", "contents": "[Soft tissue tumours on the back of the knee]. Soft tissue tumours behind the knee have rarely been described in literature. We have studied 74 patients with 79 tumours and pseudotumours in this area, and made a survey about pathology, clinical features, diagnosis, differentialdiagnosis and operative treatment. We have pointed out the varying nomenclature and confusion in definition ob a bursa and Baker's synovial herniation. The analysis of the casuistry showed predominantly gangliae, bursae and Baker's cysts. We have given special prominence to subfascial lipoma, malignant synovioma and nerve tumours as rare conditiones. Our own cases of synovioma and nerve tumours have been separately described."} {"id": "PMID:168697", "title": "[Compression arthrodesis of the knee joint].", "content": "The results of 42 cases of compression arthrodesis of the knee joint during a 5.5 years period are reviewed. Main indications were degenerative, rheumatoid and posttraumatic arthrosis and tuberculosis of the knee joint. Other differential indications and the operative procedure following the Charnley-M\u00fcller method are described. The complications - pseudarthrosis, infection, false rotation - are discussed.", "contents": "[Compression arthrodesis of the knee joint]. The results of 42 cases of compression arthrodesis of the knee joint during a 5.5 years period are reviewed. Main indications were degenerative, rheumatoid and posttraumatic arthrosis and tuberculosis of the knee joint. Other differential indications and the operative procedure following the Charnley-M\u00fcller method are described. The complications - pseudarthrosis, infection, false rotation - are discussed."} {"id": "PMID:168700", "title": "[Vacuolisation of odontoblasts and regressive metamorphoses from viewpoint of pulp-dentin system function].", "content": "The authors, after presenting a critical definition of the problems dealt with in their present paper in addition to giving an evaluation there of from the point of view of a constant increase of knowledge, describe the biological functions of the cell with particular reference to the cell's vacuolar apparatus. They then characterize the pulpodentinal system, outlining the functional adaptation of the endodontal vascular apparatus in the light of intrascopic results, the clinical importance of which is discussed at length.", "contents": "[Vacuolisation of odontoblasts and regressive metamorphoses from viewpoint of pulp-dentin system function]. The authors, after presenting a critical definition of the problems dealt with in their present paper in addition to giving an evaluation there of from the point of view of a constant increase of knowledge, describe the biological functions of the cell with particular reference to the cell's vacuolar apparatus. They then characterize the pulpodentinal system, outlining the functional adaptation of the endodontal vascular apparatus in the light of intrascopic results, the clinical importance of which is discussed at length."} {"id": "PMID:168701", "title": "[A new butyric acid-producing bacteroides species: B. splanchnicus n. sp. (author's transl)].", "content": "Three butyric acid-producing saccharolytic Bacteroides cultures (1651/6, BM 158, and IPP 3751) were described by WERNER and REICHERTZ in 1971 (Zbl.Bakt.Hyg., I. Abt. Orig. A 217,206-216). Since then, 6 strains closely resembling 1651/6 were isolated from stool specimens and surgically removed appendices. In the present communication, strains 1651/6, S2/34, S3/38, S4/28, S6/6, A5/2 are described as members of a new species, Bacteroides splanchnicus n.sp. The strains were morphologically very similar (Gram negative non-sporing non-motile rods, 1-2.5 mu in length and 0.7 mu in width) and fermented glucose, fructose, galactose, mannose, lactose, and arabinose (pH values of 4.6-5.4, moderate gas formation). Negative reactions (pH values of 5.8-7.2) were observed with 20 other carbohydrates. The strains were positive in the glutamic acid decarboxylase test and formed indole and H2S. In peptone-yeast extract broth and peptone-yeast extract-glucose broth acetic, propionic, isobutyric, butyric, and isovaleric acids were produced. Washed cells of strains 1651/6 and S4/28 incubated anaerobically in sterile solutions of single amino acids produced butyrate from lysine only. Abundant butyric acid was also produced from glucose. The in vitro activity of 15 antibiotics on 5 strains was studied by broth dilution tests. Uniformly, the strains showed resistance to aminoglycosides and polymyxins (MIC values, 60-500 mug/ml) and susceptibility to tetracyclines, lincomycin, clindamycin, rifampicin, and erythromycin (MIC values, 0.05-0.5 mug/ml). Chloramphenicol, penicillins, and cephalosporins showed bacteriostatic activity at concentrations of 5-40 mug/ml. The serological behaviour of 5 strains was studied in cross-agglutination and gel-diffusion experiments. Cross-reactivity was pronounced in gel-diffusion tests using rabbit antisera and autoclaved extracts and extracts prepared by repeated deep-freezing and thawing of whole cell suspensions as antigens. However, antisera against the B. splanchnicus strains did not react with antigens of B. fragilis 6869, B. thetaiotaomicron AS 126, B. vulgatus AM 45 a, B. distasonis AII 104 and butyric acid-producing strains BM 158 and IPP 3751 in agglutination and gel-diffusion experiments, and there were no cross-reactions between B. splanchnicus antigens and antisera against B. fragilis 6869 and the other aforementioned strains. The new species has been confirmed by members of the ICSB Taxonomic Subcommittee for Gram negative anaerobic rods. Strains 1651/6 and S4/28 have been deposited in The National Collection of Type Cultures, London (NCTC numbers 10825 and 10826). Strain NCTC 10825 (= 1651/6) is the type of the species, B. splanchnicus.", "contents": "[A new butyric acid-producing bacteroides species: B. splanchnicus n. sp. (author's transl)]. Three butyric acid-producing saccharolytic Bacteroides cultures (1651/6, BM 158, and IPP 3751) were described by WERNER and REICHERTZ in 1971 (Zbl.Bakt.Hyg., I. Abt. Orig. A 217,206-216). Since then, 6 strains closely resembling 1651/6 were isolated from stool specimens and surgically removed appendices. In the present communication, strains 1651/6, S2/34, S3/38, S4/28, S6/6, A5/2 are described as members of a new species, Bacteroides splanchnicus n.sp. The strains were morphologically very similar (Gram negative non-sporing non-motile rods, 1-2.5 mu in length and 0.7 mu in width) and fermented glucose, fructose, galactose, mannose, lactose, and arabinose (pH values of 4.6-5.4, moderate gas formation). Negative reactions (pH values of 5.8-7.2) were observed with 20 other carbohydrates. The strains were positive in the glutamic acid decarboxylase test and formed indole and H2S. In peptone-yeast extract broth and peptone-yeast extract-glucose broth acetic, propionic, isobutyric, butyric, and isovaleric acids were produced. Washed cells of strains 1651/6 and S4/28 incubated anaerobically in sterile solutions of single amino acids produced butyrate from lysine only. Abundant butyric acid was also produced from glucose. The in vitro activity of 15 antibiotics on 5 strains was studied by broth dilution tests. Uniformly, the strains showed resistance to aminoglycosides and polymyxins (MIC values, 60-500 mug/ml) and susceptibility to tetracyclines, lincomycin, clindamycin, rifampicin, and erythromycin (MIC values, 0.05-0.5 mug/ml). Chloramphenicol, penicillins, and cephalosporins showed bacteriostatic activity at concentrations of 5-40 mug/ml. The serological behaviour of 5 strains was studied in cross-agglutination and gel-diffusion experiments. Cross-reactivity was pronounced in gel-diffusion tests using rabbit antisera and autoclaved extracts and extracts prepared by repeated deep-freezing and thawing of whole cell suspensions as antigens. However, antisera against the B. splanchnicus strains did not react with antigens of B. fragilis 6869, B. thetaiotaomicron AS 126, B. vulgatus AM 45 a, B. distasonis AII 104 and butyric acid-producing strains BM 158 and IPP 3751 in agglutination and gel-diffusion experiments, and there were no cross-reactions between B. splanchnicus antigens and antisera against B. fragilis 6869 and the other aforementioned strains. The new species has been confirmed by members of the ICSB Taxonomic Subcommittee for Gram negative anaerobic rods. Strains 1651/6 and S4/28 have been deposited in The National Collection of Type Cultures, London (NCTC numbers 10825 and 10826). Strain NCTC 10825 (= 1651/6) is the type of the species, B. splanchnicus."} {"id": "PMID:168706", "title": "Oxidation processes and ubiquinone localization in the branched respiratory system of mi-1 mutant of Neurospora crassa.", "content": "1. Stimulation of succinate oxidation in mi-1 mitochondria by Mg2+ and Pi is abolished on uncoupling, which points to the energy-linked activation of succinate oxidation. 2. Mitochondria exhibited respiratory control with succinate and NADH when the cyanide-insensitive oxidation was inhibited by salicylhydroxamic acid (SHAM). SHAM lowered the oxidation rate with NADH and succinate to the same level, though the NADH oxidation rate was 2.5 times as high as with succinate. 3. Despite the high stimulation of succinate oxidation via the SHAM-sensitive pathway in the active and controlled state of mitochondria, the redox state of UQ in all metabolic states remains unchanged. On inhibition of the cyanide-insensitive pathway, UQ reduction is greatly increased only in the controlled and active state. With NADH as a substrate, UQ does not respond to the metabolic states of mitochondria. 4. The redox changes of cytochrome c parallel those of UQ. 5. Branching of the respiratory chain in mi-1 mitochondria is discussed.", "contents": "Oxidation processes and ubiquinone localization in the branched respiratory system of mi-1 mutant of Neurospora crassa. 1. Stimulation of succinate oxidation in mi-1 mitochondria by Mg2+ and Pi is abolished on uncoupling, which points to the energy-linked activation of succinate oxidation. 2. Mitochondria exhibited respiratory control with succinate and NADH when the cyanide-insensitive oxidation was inhibited by salicylhydroxamic acid (SHAM). SHAM lowered the oxidation rate with NADH and succinate to the same level, though the NADH oxidation rate was 2.5 times as high as with succinate. 3. Despite the high stimulation of succinate oxidation via the SHAM-sensitive pathway in the active and controlled state of mitochondria, the redox state of UQ in all metabolic states remains unchanged. On inhibition of the cyanide-insensitive pathway, UQ reduction is greatly increased only in the controlled and active state. With NADH as a substrate, UQ does not respond to the metabolic states of mitochondria. 4. The redox changes of cytochrome c parallel those of UQ. 5. Branching of the respiratory chain in mi-1 mitochondria is discussed."} {"id": "PMID:168707", "title": "Universality of gonadotropic hormone effect. Effect of mammalian FSH on the ovotestis of the snail Helix pomatia.", "content": "Gonadotropic hormone (FSH) stimulated markedly spermatogenesis in the ovotestis of snails. This is indicative of the presence of receptors sensitive to gonadotropic hormone in snail spermatogonia. FSH had no influence on oogenesis.", "contents": "Universality of gonadotropic hormone effect. Effect of mammalian FSH on the ovotestis of the snail Helix pomatia. Gonadotropic hormone (FSH) stimulated markedly spermatogenesis in the ovotestis of snails. This is indicative of the presence of receptors sensitive to gonadotropic hormone in snail spermatogonia. FSH had no influence on oogenesis."} {"id": "PMID:168705", "title": "[Respiratory muscle activity in newborn children during sleep and wakefulness].", "content": "Two types of electrical activity - inspiratory and tonic (postural) ones - have been registered in the external intercostal muscles and diaphragm. Both types of the activity decrease during orthodoxical sleep as compared with the period of quiet awakefulness. During the transition of orthodoxical sleep into paradoxical one, tonic activity is completely inhibited, while inspiratory activity in the intercostal muscles remains unchanged, being increased in the diaphragm. In the period of rapid eye movements inspiratory activity of the intercostal muscles is reduced. The decreased tone of the intercostal muscles accounts for changes in respiratory movements and for the onset of asynchoronous thoracic and abdominal respiratory movements during paradoxical sleep.", "contents": "[Respiratory muscle activity in newborn children during sleep and wakefulness]. Two types of electrical activity - inspiratory and tonic (postural) ones - have been registered in the external intercostal muscles and diaphragm. Both types of the activity decrease during orthodoxical sleep as compared with the period of quiet awakefulness. During the transition of orthodoxical sleep into paradoxical one, tonic activity is completely inhibited, while inspiratory activity in the intercostal muscles remains unchanged, being increased in the diaphragm. In the period of rapid eye movements inspiratory activity of the intercostal muscles is reduced. The decreased tone of the intercostal muscles accounts for changes in respiratory movements and for the onset of asynchoronous thoracic and abdominal respiratory movements during paradoxical sleep."} {"id": "PMID:168708", "title": "[Multiple malignant tumors].", "content": "The cases of six tumour patients are presented. One patient had four, the others three or two primary cancers in 12 years. The importance of keeping operated patients under supervision is pointed out and it is stressed that on the appearance of a new tumour the physician must not suppose incurability. In the case of gastrointestinal malignomas attention should be paid to cancer to the skin.", "contents": "[Multiple malignant tumors]. The cases of six tumour patients are presented. One patient had four, the others three or two primary cancers in 12 years. The importance of keeping operated patients under supervision is pointed out and it is stressed that on the appearance of a new tumour the physician must not suppose incurability. In the case of gastrointestinal malignomas attention should be paid to cancer to the skin."} {"id": "PMID:168709", "title": "Short-loop feedback mechanism of luteinizing hormone: LH stimulated hypothalamic L-cystine arylamidase to inactivate LH-RH in the rat hypothalamus.", "content": "The effect of the intravenous administration of several hormones on L-cystine arylamidase in the hypothalamus of the rat was examined. The injection of 10 mug LH into adult male and female rats was followed within 90 min by an increase of the enzyme activity by 50%, while infantile animals were not affected. When prepuberal rats were pretreated sc with testosterone and progesterone. The iv injection of 0.1 mug oestradiol-17beta into female, and of 0.5 mug testosterone into male intact mature rats also resulted in an increase of hypothalamic enzyme activity. The maximal increase in enzyme activity was seen 16 h after steroid treatment. As it had previously been shown that L-cystine arylamidase inactivates LH-RH, it may be assumed that this enzyme is involved in the short-loop feedback of LH. This assumption is based on the observation that an elevation of plasma LH brings about an activation of the enzyme system, which subsequently leads to an increased inactivation of LH-RH in the hypothalamus. This mechanism seems to depend on the presence of certain plasma levels of oestrogen in female, and of testosterone in male animals.", "contents": "Short-loop feedback mechanism of luteinizing hormone: LH stimulated hypothalamic L-cystine arylamidase to inactivate LH-RH in the rat hypothalamus. The effect of the intravenous administration of several hormones on L-cystine arylamidase in the hypothalamus of the rat was examined. The injection of 10 mug LH into adult male and female rats was followed within 90 min by an increase of the enzyme activity by 50%, while infantile animals were not affected. When prepuberal rats were pretreated sc with testosterone and progesterone. The iv injection of 0.1 mug oestradiol-17beta into female, and of 0.5 mug testosterone into male intact mature rats also resulted in an increase of hypothalamic enzyme activity. The maximal increase in enzyme activity was seen 16 h after steroid treatment. As it had previously been shown that L-cystine arylamidase inactivates LH-RH, it may be assumed that this enzyme is involved in the short-loop feedback of LH. This assumption is based on the observation that an elevation of plasma LH brings about an activation of the enzyme system, which subsequently leads to an increased inactivation of LH-RH in the hypothalamus. This mechanism seems to depend on the presence of certain plasma levels of oestrogen in female, and of testosterone in male animals."} {"id": "PMID:168710", "title": "The specificity and application of a radioimmunoassay for the alpha-subunit of luteinizing hormone in man.", "content": "A sensitive radioimmunoassay for the alpha-subunit of LH has been developed. Differences in the immunopotency of LH, FSH, and subunit preparations were found and are described in detail. The assay has been applied to the measurement of circulating levels of alpha-subunit; higher levels of alpha-subunit were found in post-menopausal than in pre-menopausal women, or men, and a rise in alpha-subunit was seen after LH-RH but not TRH administration. Elevated levels of free alpha-subunit were found in foetal cord blood at term. These results suggest that the alpha-subunit circulates independently of the intact pituitary and placental glycoprotein hormones.", "contents": "The specificity and application of a radioimmunoassay for the alpha-subunit of luteinizing hormone in man. A sensitive radioimmunoassay for the alpha-subunit of LH has been developed. Differences in the immunopotency of LH, FSH, and subunit preparations were found and are described in detail. The assay has been applied to the measurement of circulating levels of alpha-subunit; higher levels of alpha-subunit were found in post-menopausal than in pre-menopausal women, or men, and a rise in alpha-subunit was seen after LH-RH but not TRH administration. Elevated levels of free alpha-subunit were found in foetal cord blood at term. These results suggest that the alpha-subunit circulates independently of the intact pituitary and placental glycoprotein hormones."} {"id": "PMID:168711", "title": "Influence of corticotrophin on urinary 17-ketosteroid excretion in adrenalectomized females.", "content": "Urinary excretion of 17-ketosteroids was measured during dexamethasone substitution followed by ACTH (Synacthen Depot, 1 mg daily) in 10 non-virilized adrenalectomized women. No significant changes could be demonstrated indicating ovarian androgenic dependence of ACTH in non-virilized females.", "contents": "Influence of corticotrophin on urinary 17-ketosteroid excretion in adrenalectomized females. Urinary excretion of 17-ketosteroids was measured during dexamethasone substitution followed by ACTH (Synacthen Depot, 1 mg daily) in 10 non-virilized adrenalectomized women. No significant changes could be demonstrated indicating ovarian androgenic dependence of ACTH in non-virilized females."} {"id": "PMID:168712", "title": "The effects of LH-RH on the concentration of 3',5'-cyclic AMP and RNA synthesis in rat anterior pituitary.", "content": "In an experiment performed to investigate the effect of LH-RH on the anterior pituitary of rats, we studied the changes in the concentration of 3',5'-cyclic AMP in the anterior pituitary and the uridine uptake by the anterior pituitary following the intravenous injection of 100 ng LH-RH. The results obtained are summarized as follows: 1) The tissue level of 3',5'-cyclic AMP in the anterior pituitary reached the highest peak 15 min after the injection of LH-RH. 2) The uridine uptake of the anterior pituitary began to increase 15 min after the LH-RH injection and attained a maximum level (5 to 6 times the normal level) in 30 min. 3) The fact that the uridine uptake was inhibited to a considerable extent by the addition of actinomycin D to the incubation medium suggested that uridine was incorporated into the RNA fraction.", "contents": "The effects of LH-RH on the concentration of 3',5'-cyclic AMP and RNA synthesis in rat anterior pituitary. In an experiment performed to investigate the effect of LH-RH on the anterior pituitary of rats, we studied the changes in the concentration of 3',5'-cyclic AMP in the anterior pituitary and the uridine uptake by the anterior pituitary following the intravenous injection of 100 ng LH-RH. The results obtained are summarized as follows: 1) The tissue level of 3',5'-cyclic AMP in the anterior pituitary reached the highest peak 15 min after the injection of LH-RH. 2) The uridine uptake of the anterior pituitary began to increase 15 min after the LH-RH injection and attained a maximum level (5 to 6 times the normal level) in 30 min. 3) The fact that the uridine uptake was inhibited to a considerable extent by the addition of actinomycin D to the incubation medium suggested that uridine was incorporated into the RNA fraction."} {"id": "PMID:168713", "title": "The importance of sodium balance on the effect of angiotensin II on aldosterone production.", "content": "The action of angiotensin II on the adrenal cortex can be modified by body sodium balance. The secretion rate of aldosterone was compared with the late biosynthetic pathway in dogs kept under different sodium states. The conversion of corticosterone (B) to aldosterone was significantly increased by the infusion of angiotensin II into sodium depleted dogs. ACTH infusion failed to increase the late aldosterone pathway in sodium depleted animals, even though the secretion rate increased by 10 times. These results confirm previously indirect evidence that angiotensin II has a direct stimulatory effect on the late step of aldosterone biosynthesis. This stimulation does not appear to be the result of enzyme-substrate activation by aldosterone precursors. The results favour the hypothesis that sodium balance can modulate the action of angiotensin II not only on the first steps, but that there is also a regulatory effect on the conversion of corticosterone to aldosterone.", "contents": "The importance of sodium balance on the effect of angiotensin II on aldosterone production. The action of angiotensin II on the adrenal cortex can be modified by body sodium balance. The secretion rate of aldosterone was compared with the late biosynthetic pathway in dogs kept under different sodium states. The conversion of corticosterone (B) to aldosterone was significantly increased by the infusion of angiotensin II into sodium depleted dogs. ACTH infusion failed to increase the late aldosterone pathway in sodium depleted animals, even though the secretion rate increased by 10 times. These results confirm previously indirect evidence that angiotensin II has a direct stimulatory effect on the late step of aldosterone biosynthesis. This stimulation does not appear to be the result of enzyme-substrate activation by aldosterone precursors. The results favour the hypothesis that sodium balance can modulate the action of angiotensin II not only on the first steps, but that there is also a regulatory effect on the conversion of corticosterone to aldosterone."} {"id": "PMID:168714", "title": "Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol.", "content": "In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.", "contents": "Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol. In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake."} {"id": "PMID:168715", "title": "An in vitro method to study the participation of various components in autoimmune hemolytic anemia.", "content": "A method is described which allows for the in vitro evaluation of various etiological components in autoimmune hemolytic anemia. As an example of the applicability of the technique, erythrocytes and serum from a patient with an autoimmune hemolytic anemia suspected to be due to poliovirus III were tested with poliovirus III and complement. Incubation of the patient's cells with complement, poliovirus and autologous serum was required for optimal in vitro fragility. The method is proposed as a practical and convenient in vitro technique for evaluating the participation of individual components in the pathogenesis of autoimmune hemolytic anemias.", "contents": "An in vitro method to study the participation of various components in autoimmune hemolytic anemia. A method is described which allows for the in vitro evaluation of various etiological components in autoimmune hemolytic anemia. As an example of the applicability of the technique, erythrocytes and serum from a patient with an autoimmune hemolytic anemia suspected to be due to poliovirus III were tested with poliovirus III and complement. Incubation of the patient's cells with complement, poliovirus and autologous serum was required for optimal in vitro fragility. The method is proposed as a practical and convenient in vitro technique for evaluating the participation of individual components in the pathogenesis of autoimmune hemolytic anemias."} {"id": "PMID:168716", "title": "Parallel tubular structures in lymphocytes. I. Occurrence in patients with Hodgkin's Disease.", "content": "Investigations with the electron microscope on peripheral blood of patients with Hodgkin's disease revealed parallel tubular structures in the cytoplasm of the lymphocytes, similar to those described in the literature. In normal subjects 2-9% of the lymphocytes were found to contain these structures. The number of such lymphocytes is increased in most patients as compared to normals. A correlation between an increase of inclusions containing lymphocytes and the histological or clinical classifications could not be established. An elevation of lymphocytes with tubular structures could be found in both favourable and unfavourable histological and clinical subgroups of Hodgkin patients, but especially in all groups with an unfavourable prognosis. The origin and function of the parallel tubular structures is still unknown, but their increase in lymphocytes of patients with Hodgkin's disease is of some interest in view of the involvement of these cells.", "contents": "Parallel tubular structures in lymphocytes. I. Occurrence in patients with Hodgkin's Disease. Investigations with the electron microscope on peripheral blood of patients with Hodgkin's disease revealed parallel tubular structures in the cytoplasm of the lymphocytes, similar to those described in the literature. In normal subjects 2-9% of the lymphocytes were found to contain these structures. The number of such lymphocytes is increased in most patients as compared to normals. A correlation between an increase of inclusions containing lymphocytes and the histological or clinical classifications could not be established. An elevation of lymphocytes with tubular structures could be found in both favourable and unfavourable histological and clinical subgroups of Hodgkin patients, but especially in all groups with an unfavourable prognosis. The origin and function of the parallel tubular structures is still unknown, but their increase in lymphocytes of patients with Hodgkin's disease is of some interest in view of the involvement of these cells."} {"id": "PMID:168718", "title": "Correlation between incorporation of myo-(2-3H)inositol into the phosphatidylinositol of lymphocytes and disability degree, stage and duration of multiple sclerosis.", "content": "The present study revealed a positive correlation between the degree of disability of MS patients and the rate of incorporation of myo-(2-3-H)inositol into phosphatidylinositol of lymphocytes stimulated with basic protein (BP) and phytohemagglutinin (PHA). No correlation could be found between the response of lymphocytes to measles antigen (MA) and the degree of disability, stage and duration of multiple sclerosis. No correlation could be observed between the response of lymphocytes to the stimulants studied and the duration of the disease.", "contents": "Correlation between incorporation of myo-(2-3H)inositol into the phosphatidylinositol of lymphocytes and disability degree, stage and duration of multiple sclerosis. The present study revealed a positive correlation between the degree of disability of MS patients and the rate of incorporation of myo-(2-3-H)inositol into phosphatidylinositol of lymphocytes stimulated with basic protein (BP) and phytohemagglutinin (PHA). No correlation could be found between the response of lymphocytes to measles antigen (MA) and the degree of disability, stage and duration of multiple sclerosis. No correlation could be observed between the response of lymphocytes to the stimulants studied and the duration of the disease."} {"id": "PMID:168719", "title": "Experimental parainfluenza type 1 virus-induced encephalomyelopathy in adult mouse: a histopathological study.", "content": "The pathogenicity of a strain of parainfluenza type 1 virus, isolated from the cultured brain cells from multiple sclerosis patients and designated as 6/94 virus, was studied in mouse brain. Selective degeneration of cerebral white matter, preceded by mononuclear cell infiltration, and ependymitis were prominent pathological features of the mouse intracerebrally inoculated with 6/94 virus. After inactivation by ultraviolet light the virus was still capable of producing the inflammatory and degenerative white matter lesions, although the severity of ependymitis was substantially reduced.", "contents": "Experimental parainfluenza type 1 virus-induced encephalomyelopathy in adult mouse: a histopathological study. The pathogenicity of a strain of parainfluenza type 1 virus, isolated from the cultured brain cells from multiple sclerosis patients and designated as 6/94 virus, was studied in mouse brain. Selective degeneration of cerebral white matter, preceded by mononuclear cell infiltration, and ependymitis were prominent pathological features of the mouse intracerebrally inoculated with 6/94 virus. After inactivation by ultraviolet light the virus was still capable of producing the inflammatory and degenerative white matter lesions, although the severity of ependymitis was substantially reduced."} {"id": "PMID:168720", "title": "Nuclear characteristics of malignant lymphoma in the brain.", "content": "In addition to chromatin and nucleoli, various classes of structures were often seen in nuclei of malignant lymphoma, when compared with other brain tumours. Interchromatin, perichromatin, and atypical dense granules could be ribonucleoprotein in nature on basis of their behaviours in enzymatic extraction and EDTA stain. The perichromatin fibrils became visible at the border of the condensed chromatin only after EDTA stain and might contain substrate for HnRNA. Nuclear bodies and intranuclear fibrillar rodlets also were evident.", "contents": "Nuclear characteristics of malignant lymphoma in the brain. In addition to chromatin and nucleoli, various classes of structures were often seen in nuclei of malignant lymphoma, when compared with other brain tumours. Interchromatin, perichromatin, and atypical dense granules could be ribonucleoprotein in nature on basis of their behaviours in enzymatic extraction and EDTA stain. The perichromatin fibrils became visible at the border of the condensed chromatin only after EDTA stain and might contain substrate for HnRNA. Nuclear bodies and intranuclear fibrillar rodlets also were evident."} {"id": "PMID:168717", "title": "Paradoxical sleep characteristics and cultural environment. Preliminary results.", "content": "The Temiars are a tribe of negroid pygmies of basically Proto-Malaysian affinities. Field-work in the Malaysian jungle provided some observations on the sleep-wakefulness cycle of two young Temiar adults. This cycle was monophasic circumstances permitting. Their rest-activity cycle at night was similar in the jungle and in the laboratory. Polygraphic total night-sleep recordings were made with both of them in the EEG laboratory in the Hospital Besar in Kuala Lumpur. The eye-movement frequencies of PS were compared with those from young adults of the West. Although the differences were not statistically significant, the Rem-densities of the Temiars were constantly at the low side. The significance of the results are being discussed.", "contents": "Paradoxical sleep characteristics and cultural environment. Preliminary results. The Temiars are a tribe of negroid pygmies of basically Proto-Malaysian affinities. Field-work in the Malaysian jungle provided some observations on the sleep-wakefulness cycle of two young Temiar adults. This cycle was monophasic circumstances permitting. Their rest-activity cycle at night was similar in the jungle and in the laboratory. Polygraphic total night-sleep recordings were made with both of them in the EEG laboratory in the Hospital Besar in Kuala Lumpur. The eye-movement frequencies of PS were compared with those from young adults of the West. Although the differences were not statistically significant, the Rem-densities of the Temiars were constantly at the low side. The significance of the results are being discussed."} {"id": "PMID:168721", "title": "Morphological classification of malignant lymphomas: ultrastructural, cytochemical and immunological results.", "content": "Except for tumors clearly producing immunoglobulin (e.g. plasma-cytoma), the different classes of malignant lymphomas do not correlate with a constant surface immunoglobulin pattern. Beside a prevailing IgM-surface type in a high number of different lymphoma classes even T-like or O-cells occur in most tumor types provided they are studied in a sufficient number. The possibility of dedifferentiation of immunologic cell qualities has to be envisaged. In this context intracellular lambda-chain crystals occurring in chronic lymphocytic leukaemia may provide a morphological hallmark of anaplastic deterioration of immunoglobulin synthesis. - The ambiguous significance of PAS-positive inclusions and virus-like microtubular complexes in lymphoma cells is discussed. - In conclusion the recent discovery of hairy cell leukaemia provides a good example of the value of nomenclatures based on empiricism rather than on short-lived theories.", "contents": "Morphological classification of malignant lymphomas: ultrastructural, cytochemical and immunological results. Except for tumors clearly producing immunoglobulin (e.g. plasma-cytoma), the different classes of malignant lymphomas do not correlate with a constant surface immunoglobulin pattern. Beside a prevailing IgM-surface type in a high number of different lymphoma classes even T-like or O-cells occur in most tumor types provided they are studied in a sufficient number. The possibility of dedifferentiation of immunologic cell qualities has to be envisaged. In this context intracellular lambda-chain crystals occurring in chronic lymphocytic leukaemia may provide a morphological hallmark of anaplastic deterioration of immunoglobulin synthesis. - The ambiguous significance of PAS-positive inclusions and virus-like microtubular complexes in lymphoma cells is discussed. - In conclusion the recent discovery of hairy cell leukaemia provides a good example of the value of nomenclatures based on empiricism rather than on short-lived theories."} {"id": "PMID:168722", "title": "Origin of brain macrophages and the nature of the so-called microglia.", "content": "Two aspects of the so-called microglia were studied by silver impregnation and 3H-TdR ARG in light and electron microscopy. (1) So-called microglioblasts are glioblasts differentiated from matrix cells. They are progenitors of the so-called resting microglia as well as of astrocytes and oligodendroglia. (2) Brain macrophages in stab wounds, experimental Japanese encephalitis and retrograde degeneration of the facial nucleus are all found to be of hematogenous origin. Infiltrating hematogenous cells cannot stay permanently in the brain parenchyma unless pathological alterations persist indefinitely.", "contents": "Origin of brain macrophages and the nature of the so-called microglia. Two aspects of the so-called microglia were studied by silver impregnation and 3H-TdR ARG in light and electron microscopy. (1) So-called microglioblasts are glioblasts differentiated from matrix cells. They are progenitors of the so-called resting microglia as well as of astrocytes and oligodendroglia. (2) Brain macrophages in stab wounds, experimental Japanese encephalitis and retrograde degeneration of the facial nucleus are all found to be of hematogenous origin. Infiltrating hematogenous cells cannot stay permanently in the brain parenchyma unless pathological alterations persist indefinitely."} {"id": "PMID:168723", "title": "Primary lymphoreticuloses of the nervous system in animals.", "content": "Lymphoreticular proliferative disorders occur in most species of animals including submammalian vertebrates but only occasionally affect the nervous system. Primary lymphoreticular disorders of the nervous system have been recognized in chickens as a herpesvirus-induced avian neurolymphomatosis and in mammals, patricularly in the dog, as reticulum cell sarcomas originating from perivascular mesenchymal precursor cells. Criteria have been discussed to distinguish neoplastic from inflammatory lymphoreticuloses but borderline cases exist where a clear distinction is not always possible.", "contents": "Primary lymphoreticuloses of the nervous system in animals. Lymphoreticular proliferative disorders occur in most species of animals including submammalian vertebrates but only occasionally affect the nervous system. Primary lymphoreticular disorders of the nervous system have been recognized in chickens as a herpesvirus-induced avian neurolymphomatosis and in mammals, patricularly in the dog, as reticulum cell sarcomas originating from perivascular mesenchymal precursor cells. Criteria have been discussed to distinguish neoplastic from inflammatory lymphoreticuloses but borderline cases exist where a clear distinction is not always possible."} {"id": "PMID:168725", "title": "Hereditary ornithine transcarbamylase deficiency. Report of two male cases with residual enzymatic activity.", "content": "The authors report two male cases of liver ornithine carbamyl transferase deficiency. In one the disease occurred at 8 years of age with hyperammoniemic coma leading to death in 48 hours. In the second case, symptoms appeared on the sixth day of life but the outcome was favorable. The child is normal at 15 months. In both cases, there was a residual 6-10% OCT activity. These observations are similar to two other male cases in the literature and are different from the male neonatal fatal form in which the deficiency is virtually total. They underline the genetically heterogeneous nature of OCT deficiencies and the fact that in this X-transmitted trait, hemizygotes can preserve a functional enzymatic activity compatible with life.", "contents": "Hereditary ornithine transcarbamylase deficiency. Report of two male cases with residual enzymatic activity. The authors report two male cases of liver ornithine carbamyl transferase deficiency. In one the disease occurred at 8 years of age with hyperammoniemic coma leading to death in 48 hours. In the second case, symptoms appeared on the sixth day of life but the outcome was favorable. The child is normal at 15 months. In both cases, there was a residual 6-10% OCT activity. These observations are similar to two other male cases in the literature and are different from the male neonatal fatal form in which the deficiency is virtually total. They underline the genetically heterogeneous nature of OCT deficiencies and the fact that in this X-transmitted trait, hemizygotes can preserve a functional enzymatic activity compatible with life."} {"id": "PMID:168726", "title": "Sympus monopus accompanied by nephroblastoma--A case report.", "content": "An autopsy case of sirenomelia accompanied by nephroblastoma has been reported. In this case, there were many complicating anomalies such as left renal agenesis, absence of external genital organs, imperforate anus, mass of redundant skin over sacral region, two umbilical vessels, absence of great omentum and patent ductus arteriosus. We considered this malformation as sympus monopus.", "contents": "Sympus monopus accompanied by nephroblastoma--A case report. An autopsy case of sirenomelia accompanied by nephroblastoma has been reported. In this case, there were many complicating anomalies such as left renal agenesis, absence of external genital organs, imperforate anus, mass of redundant skin over sacral region, two umbilical vessels, absence of great omentum and patent ductus arteriosus. We considered this malformation as sympus monopus."} {"id": "PMID:168727", "title": "Effect of beta-propiolactone on infectivity and haemagglutinin of the BK virus.", "content": "The effect of beta-propiolactone (BPL) on the infectivity and haemagglutinating properties of BK virus was studied. No virus multiplication was observed when Vero cell cultures were inoculated with virus treated with 0.1 per cent or higher concentration of BPL. On the other hand, treatment of BK virus with 0.1 per cent or lower concentration of BPL had no apparent effect on viral haemagglutinin. BPL at a concentration of 0.1 per cent could therefore be used to prepare BK virus haemagglutinin which contains little or no infectious virus. Inactivated haemagglutinin seems to be somewhat labile against freezing and thawing, but storage at 4 degrees C had no effect on it. Identical haemagglutination inhibiting antibody titres were obtained when human sera were tested with standard haemagglutinin or with haemagglutinin inactivated with BPL.", "contents": "Effect of beta-propiolactone on infectivity and haemagglutinin of the BK virus. The effect of beta-propiolactone (BPL) on the infectivity and haemagglutinating properties of BK virus was studied. No virus multiplication was observed when Vero cell cultures were inoculated with virus treated with 0.1 per cent or higher concentration of BPL. On the other hand, treatment of BK virus with 0.1 per cent or lower concentration of BPL had no apparent effect on viral haemagglutinin. BPL at a concentration of 0.1 per cent could therefore be used to prepare BK virus haemagglutinin which contains little or no infectious virus. Inactivated haemagglutinin seems to be somewhat labile against freezing and thawing, but storage at 4 degrees C had no effect on it. Identical haemagglutination inhibiting antibody titres were obtained when human sera were tested with standard haemagglutinin or with haemagglutinin inactivated with BPL."} {"id": "PMID:168728", "title": "A method fof production or antisera to hepatitis b antigen subtypes, and the distribution of subtypes d and y among norwegian hepatitis b patients.", "content": "A method for production of antisera to hepatitis B antigen (HBsAg) subtypes D and Y is described. The method is based on the coupling of HBsAg to a colloidal silica gel (Aerosil), and the selective adsorption of unwanted antibodies from antisera with this preparation. Some results obtained with Norwegian hepatitis patient sera are included.", "contents": "A method fof production or antisera to hepatitis b antigen subtypes, and the distribution of subtypes d and y among norwegian hepatitis b patients. A method for production of antisera to hepatitis B antigen (HBsAg) subtypes D and Y is described. The method is based on the coupling of HBsAg to a colloidal silica gel (Aerosil), and the selective adsorption of unwanted antibodies from antisera with this preparation. Some results obtained with Norwegian hepatitis patient sera are included."} {"id": "PMID:168724", "title": "Recruitment in conduction deafness. Observations using a midline loudness balance test.", "content": "A midline loudness balance test was made in 10 normal ears with blocked ear canals and in 104 conductively deaf ears with loss not exceeding 45 dB. The test was made by giving the tones simultaneously in the ears at 10, 60 and 80 dB sensation levels for 500 and 2 000 Hz. In the normal group the midline balance method indicated no reduction from the threshold differences at any of the three levels whereas significant reductions occurred in all groups of conduction deafness. The occurrence of true partial recruitment in conduction deafness demonstrated by ABLB (Fowler's) test was attributed to altered middle ear mechanics, loud tones stimulating the inner ear relatively more effectively than tones near the threshold level. The midline balance method is more closely dependent upon bone conducted sounds and on the altered relative movements of the labyrinthine windows.", "contents": "Recruitment in conduction deafness. Observations using a midline loudness balance test. A midline loudness balance test was made in 10 normal ears with blocked ear canals and in 104 conductively deaf ears with loss not exceeding 45 dB. The test was made by giving the tones simultaneously in the ears at 10, 60 and 80 dB sensation levels for 500 and 2 000 Hz. In the normal group the midline balance method indicated no reduction from the threshold differences at any of the three levels whereas significant reductions occurred in all groups of conduction deafness. The occurrence of true partial recruitment in conduction deafness demonstrated by ABLB (Fowler's) test was attributed to altered middle ear mechanics, loud tones stimulating the inner ear relatively more effectively than tones near the threshold level. The midline balance method is more closely dependent upon bone conducted sounds and on the altered relative movements of the labyrinthine windows."} {"id": "PMID:168729", "title": "Studies on the growth of feline panleukopaenia virus in cell cultures.", "content": "The growth of feline panleukopaenia virus was examined in relation to various cell growth curves of secondary feline kidney cells. In cell cultures with a high mitotic index, the manifestation of virus infection, expressed as percentage number of cells with inclusion bodies, was correspondingly high. In cultures with low mitotic index, the percentage number of cells with inclusion bodies was low. A cytopathic effect was seen by inoculation of virus with a titre of 10-3-5TCID-50/ML. This effect was most pronounced using cell cultures seeded in a quantity of 1 million cells per ml to 500,000 cells per ml with inoculation made during the first 24 hours after seeding when the mitotic index was high. Both the cytopathic effect and the occurrence of inclusion bodies were of transient nature. The peak of infection, both with regard to the cytopathic effect and the percentage number of cells with inclusion bodies, was seen three days after inoculation.", "contents": "Studies on the growth of feline panleukopaenia virus in cell cultures. The growth of feline panleukopaenia virus was examined in relation to various cell growth curves of secondary feline kidney cells. In cell cultures with a high mitotic index, the manifestation of virus infection, expressed as percentage number of cells with inclusion bodies, was correspondingly high. In cultures with low mitotic index, the percentage number of cells with inclusion bodies was low. A cytopathic effect was seen by inoculation of virus with a titre of 10-3-5TCID-50/ML. This effect was most pronounced using cell cultures seeded in a quantity of 1 million cells per ml to 500,000 cells per ml with inoculation made during the first 24 hours after seeding when the mitotic index was high. Both the cytopathic effect and the occurrence of inclusion bodies were of transient nature. The peak of infection, both with regard to the cytopathic effect and the percentage number of cells with inclusion bodies, was seen three days after inoculation."} {"id": "PMID:168730", "title": "Comparison of neutralizing and immunoprecipitating activity in guinea pig antisera against Herpes simplex virus types 1 and 2.", "content": "Guinea pig antisera against Herpes simplex virus (HSV) types 1 and 2 were compared in neutralization tests and crossed immunoelectrophoresis. It was found that the HSV type specific neutralization of guinea pig antisera could be associated with the precipitating activity to HSV type 1 and 2 glycoproteins.", "contents": "Comparison of neutralizing and immunoprecipitating activity in guinea pig antisera against Herpes simplex virus types 1 and 2. Guinea pig antisera against Herpes simplex virus (HSV) types 1 and 2 were compared in neutralization tests and crossed immunoelectrophoresis. It was found that the HSV type specific neutralization of guinea pig antisera could be associated with the precipitating activity to HSV type 1 and 2 glycoproteins."} {"id": "PMID:168731", "title": "Transplantable hamster tumors induced with the BK virus.", "content": "Two tumors induced by BK virus in hamsters of an inbred strain were serially transplanted by subcutaneous injection of tumor explants. Both the original tumors as well as the transplants grew as solid, localized, encapsulated tumors. Histologically tumors were classified as fusocellular fibrosarcomas. Polymorphic tumor tissue was by an abundance of collagen fibers and multinucleated giant cells. Cell lines established from tumors contained nuclear T antigen which stained with sera from a number of tumor-carrying hamsters, but also with SV40 T antiserum. Viron antigens were not detected in these cell lines, and no virus was isolated when tumor extracts were inoculated in Vero cells.", "contents": "Transplantable hamster tumors induced with the BK virus. Two tumors induced by BK virus in hamsters of an inbred strain were serially transplanted by subcutaneous injection of tumor explants. Both the original tumors as well as the transplants grew as solid, localized, encapsulated tumors. Histologically tumors were classified as fusocellular fibrosarcomas. Polymorphic tumor tissue was by an abundance of collagen fibers and multinucleated giant cells. Cell lines established from tumors contained nuclear T antigen which stained with sera from a number of tumor-carrying hamsters, but also with SV40 T antiserum. Viron antigens were not detected in these cell lines, and no virus was isolated when tumor extracts were inoculated in Vero cells."} {"id": "PMID:168734", "title": "Levels of cyclic AMP and electrical events during inhibition of contractile activity in vascular smooth muscle.", "content": "The possible relationship between changes in electrical and mechanical activity and in tissue levels of cyclic AMP (cAMP) during relaxation of the myogenical active rat portal vein has been elucidated in response to different inhibitory stimuli. Isoproterenol, 10(-5) M, caused an initial pronounced inhibition of spike discharge and contractions followed by a partial recover over the 15 min exposure period. This inhibitory response was associated with doubling of tissue cAMP after 1 min and a less pronounced increase in later measurements (5 and 15 min). Papaverine, 10(-4)M, caused, in contrast, an inhibition of electrical and mechanical activity which developed gradually over the entire 15 min exposure period. The levels of cAMP at 1,5 and 15 min all exceeded the corresponding values obtained with isoproterenol. The two drugs in combination gave a biphasic inhibitory response associated with a sustained large increase in the level of cAMP. These drug induced inhibitions were thus accompanied by increased levels of cAMP, but the different time courses of the electromechanical responses could not be rlated to corresponding variations in the content of cAMP. Hyperosmolality (+150 mM sucrose) and mechanical vibration (100 Hz) elicited differentiated inhibitions of smooth muscle activity without changes in tissue cAMP. The mechanical effects elicited by isoproterenol, papaverine and hyperosmolality were accompanied by approximately parallel changes in electrical spike discharge. It is concluded that increased levels of cAMP are not indispensible for vascular smooth muscle relaxation, and that the magnitude of pharmacologically induced inhibitions are not always closely related to the total tissue content of the nucleotide.", "contents": "Levels of cyclic AMP and electrical events during inhibition of contractile activity in vascular smooth muscle. The possible relationship between changes in electrical and mechanical activity and in tissue levels of cyclic AMP (cAMP) during relaxation of the myogenical active rat portal vein has been elucidated in response to different inhibitory stimuli. Isoproterenol, 10(-5) M, caused an initial pronounced inhibition of spike discharge and contractions followed by a partial recover over the 15 min exposure period. This inhibitory response was associated with doubling of tissue cAMP after 1 min and a less pronounced increase in later measurements (5 and 15 min). Papaverine, 10(-4)M, caused, in contrast, an inhibition of electrical and mechanical activity which developed gradually over the entire 15 min exposure period. The levels of cAMP at 1,5 and 15 min all exceeded the corresponding values obtained with isoproterenol. The two drugs in combination gave a biphasic inhibitory response associated with a sustained large increase in the level of cAMP. These drug induced inhibitions were thus accompanied by increased levels of cAMP, but the different time courses of the electromechanical responses could not be rlated to corresponding variations in the content of cAMP. Hyperosmolality (+150 mM sucrose) and mechanical vibration (100 Hz) elicited differentiated inhibitions of smooth muscle activity without changes in tissue cAMP. The mechanical effects elicited by isoproterenol, papaverine and hyperosmolality were accompanied by approximately parallel changes in electrical spike discharge. It is concluded that increased levels of cAMP are not indispensible for vascular smooth muscle relaxation, and that the magnitude of pharmacologically induced inhibitions are not always closely related to the total tissue content of the nucleotide."} {"id": "PMID:168735", "title": "Plasma renin activity and in vitro synthesis of aldosterone by the adrenal glands of rats with spontaneous, renal, or pinealectomy-induced hypertension.", "content": "In the present study a comparison was made on the role of the renin-aldosterone system in rats with various forms of experimental hypertension (pinealectomy-induced, renal and spontaneous). The plasma sodium and potassium concentrations as well as renin activity were measured. The in vitro production of aldosterone by quartered adrenal glands of these rats was also determined. 5 weeks after the operations the blood pressure of the pinealectomized and renal operated rats was significantly increased. The plasma sodium concentration did not differ in various groups, but that of potassium was decreased in the renal hypertensive animals. The plasma renin activity of the pinealectomized rats was elevated while in other forms of hypertension it was at the control level. The basal aldosterone production by the adrenal quarters was equal in all the groups. ACTH, dibutyryl cyclic adenosine-3',5'-monophosphate (DBA) and 5HT stimulated the aldosterone production. The responses to ACTH and DBA were greater in the adrenals of renal hypertensive rats than in the other forms of hypertension or in the controls. We suggest that the renin-aldosterone system is of importance in the maintenance of renal hypertension, while in pinealectomy-induced hypertension elevated plasma renin activity reflects an increased sympathetic activity which probably is the main cause of hypertension in these animals.", "contents": "Plasma renin activity and in vitro synthesis of aldosterone by the adrenal glands of rats with spontaneous, renal, or pinealectomy-induced hypertension. In the present study a comparison was made on the role of the renin-aldosterone system in rats with various forms of experimental hypertension (pinealectomy-induced, renal and spontaneous). The plasma sodium and potassium concentrations as well as renin activity were measured. The in vitro production of aldosterone by quartered adrenal glands of these rats was also determined. 5 weeks after the operations the blood pressure of the pinealectomized and renal operated rats was significantly increased. The plasma sodium concentration did not differ in various groups, but that of potassium was decreased in the renal hypertensive animals. The plasma renin activity of the pinealectomized rats was elevated while in other forms of hypertension it was at the control level. The basal aldosterone production by the adrenal quarters was equal in all the groups. ACTH, dibutyryl cyclic adenosine-3',5'-monophosphate (DBA) and 5HT stimulated the aldosterone production. The responses to ACTH and DBA were greater in the adrenals of renal hypertensive rats than in the other forms of hypertension or in the controls. We suggest that the renin-aldosterone system is of importance in the maintenance of renal hypertension, while in pinealectomy-induced hypertension elevated plasma renin activity reflects an increased sympathetic activity which probably is the main cause of hypertension in these animals."} {"id": "PMID:168737", "title": "Studies in asymptomatic primary hyperlipidaemia II. Clinical findings.", "content": "A clinical and laboratory examination of abnormalities not attributable to atherosclerosis has been performed on 188 male and 126 female adult subjects with hyperlipidaemia. The sample was recruited from 20000 subjects screened at a health control centre who had an initial serum cholesterol and/or triglyceride (TG) concentration above 350 mg/100 ml and 3.50 mmol/l. All were subjectively healthy and had no history of atherosclerotic disease. Known cases of secondary hyperlipidaemia were excluded. Lipoprotein (LP) analysis with preparative ultracentrifugation and electrophoresis was made on all subjects including control group with \"nonelevated\" serum lipids. Typing of hyperlipoproteinaemia (HLP) was performed according to the modified system of Fredrickson et al. Compared to controls, subjects who had elevated very low density ?LP (VLDL) (types II B, III, IV and V) were more obsese, while subjectI B and women with type IV HLP than in the control groups. Arcus corneae was seen in 29% of control groups. Arcus corneae was seen in 29% of controls and in higher frequencies in types II A and II B. A positive correlation existed between the frequency of arcus corneae and the mean low density LP cholesterol in the different types. Multiple tendon xanthomata (n equals 11) were found exclusively in type II A HLP, palmar xanthomata (n equals 3) only in the presence of floating beta-LP and eruptive xanthomata in one male with type V HLP. The mean ESR was increased in all types of HLP. The mean S-GPT and uric acid concentrations were higher in type IV HLP in both sexes than in the control groups. In men with type IV HLP S-GPT was positively correlated to tvldl tg. the uric acid level was correlated to both the VLDL TG concentration and body weight independently. Of the male subjects with HLP 1/3-1/2 had a diabetic or borderline i.v. glucose tolerance.", "contents": "Studies in asymptomatic primary hyperlipidaemia II. Clinical findings. A clinical and laboratory examination of abnormalities not attributable to atherosclerosis has been performed on 188 male and 126 female adult subjects with hyperlipidaemia. The sample was recruited from 20000 subjects screened at a health control centre who had an initial serum cholesterol and/or triglyceride (TG) concentration above 350 mg/100 ml and 3.50 mmol/l. All were subjectively healthy and had no history of atherosclerotic disease. Known cases of secondary hyperlipidaemia were excluded. Lipoprotein (LP) analysis with preparative ultracentrifugation and electrophoresis was made on all subjects including control group with \"nonelevated\" serum lipids. Typing of hyperlipoproteinaemia (HLP) was performed according to the modified system of Fredrickson et al. Compared to controls, subjects who had elevated very low density ?LP (VLDL) (types II B, III, IV and V) were more obsese, while subjectI B and women with type IV HLP than in the control groups. Arcus corneae was seen in 29% of control groups. Arcus corneae was seen in 29% of controls and in higher frequencies in types II A and II B. A positive correlation existed between the frequency of arcus corneae and the mean low density LP cholesterol in the different types. Multiple tendon xanthomata (n equals 11) were found exclusively in type II A HLP, palmar xanthomata (n equals 3) only in the presence of floating beta-LP and eruptive xanthomata in one male with type V HLP. The mean ESR was increased in all types of HLP. The mean S-GPT and uric acid concentrations were higher in type IV HLP in both sexes than in the control groups. In men with type IV HLP S-GPT was positively correlated to tvldl tg. the uric acid level was correlated to both the VLDL TG concentration and body weight independently. Of the male subjects with HLP 1/3-1/2 had a diabetic or borderline i.v. glucose tolerance."} {"id": "PMID:168739", "title": "Effect of arginine deficiency on the reproduction of human cytomegalovirus.", "content": "In arginine-deprived human embryonic fibroblasts the reproduction cycle of human cytomegalovirus (CMV) is incomplete. Infectious virus cannot be demonstrated in cell disintergrates, and from among the CMV antigens only the diffuse cytoplasmic antigen is detectable by immunofluorescence. The antigens localized in the cell membrane and those appearing during the complete cycle as large granules or inclusion-like bodies in the nucleus do not appear in the absence of arginine. The CMV genome persists in the arginine-deprived culture; after re-feeding with arginine-containing medium, maturation of virions soon ensues. Maturation could be prevented by inhibitors of protein synthesis, but not by DNA inhibitors, added simultaneously with completion of the medium.", "contents": "Effect of arginine deficiency on the reproduction of human cytomegalovirus. In arginine-deprived human embryonic fibroblasts the reproduction cycle of human cytomegalovirus (CMV) is incomplete. Infectious virus cannot be demonstrated in cell disintergrates, and from among the CMV antigens only the diffuse cytoplasmic antigen is detectable by immunofluorescence. The antigens localized in the cell membrane and those appearing during the complete cycle as large granules or inclusion-like bodies in the nucleus do not appear in the absence of arginine. The CMV genome persists in the arginine-deprived culture; after re-feeding with arginine-containing medium, maturation of virions soon ensues. Maturation could be prevented by inhibitors of protein synthesis, but not by DNA inhibitors, added simultaneously with completion of the medium."} {"id": "PMID:168740", "title": "Post-therapeutic levels of antimicrobial drugs in faeces.", "content": "After oral administration for 3 days, furazolidone disappeared from the faeces on the first, polymyxin B and ampicillin on the fourth, and trimethoprim + sulphamethoxazole and nalidixic acid on the fifth day.", "contents": "Post-therapeutic levels of antimicrobial drugs in faeces. After oral administration for 3 days, furazolidone disappeared from the faeces on the first, polymyxin B and ampicillin on the fourth, and trimethoprim + sulphamethoxazole and nalidixic acid on the fifth day."} {"id": "PMID:168741", "title": "Virus-specific changes in mouse cells inoculated with a strain of human cytomegalovirus.", "content": "Cytopathic changes and virus-specific antigens developed in, then disappeared from, mouse fibroblasts infected by a strain of human cytomegalovirus (CMV), but their disappearance was delayed in cells treated with idoxuridine prior to infection. The replication of vesicular stomatitis virus and herpes simplex virus was restricted in human CMV-infected mouse cells as long as human CMV-specific antigens were present. Virus-specific antigens could be induced by treatment with idoxuridine or arginine deficiency in mouse cells which had previously turned \"negative\".", "contents": "Virus-specific changes in mouse cells inoculated with a strain of human cytomegalovirus. Cytopathic changes and virus-specific antigens developed in, then disappeared from, mouse fibroblasts infected by a strain of human cytomegalovirus (CMV), but their disappearance was delayed in cells treated with idoxuridine prior to infection. The replication of vesicular stomatitis virus and herpes simplex virus was restricted in human CMV-infected mouse cells as long as human CMV-specific antigens were present. Virus-specific antigens could be induced by treatment with idoxuridine or arginine deficiency in mouse cells which had previously turned \"negative\"."} {"id": "PMID:168742", "title": "Interferon induction and action in transformed poikilothermic cells.", "content": "The production and effect of interferon in the virus-transformed cell line TGk1, originating from kidney cells of Testudo gracea were studied and compared to those in the primary cell culture. West Nile virus and Newcastle disease virus were used as inducers. Interferon production in TGk1 cells began 6 hr later than in the primary cell culture and reached the maximum 64 IU, 18 hr after virus inoculation. In the primary culture, interferon production increased till the 48th hr reaching a fourfold level (256 IU). A significant reduction of the antiviral effect of interferon against vesicular stomatitis virus but not against vaccinia virus was observed in the transformed cells. The decreased interferon production and effect in TGk1 cells is regarded as a consequence of the disturbance of the interferon regulatory mechanism taking place as a result of the virus-induced transformation.", "contents": "Interferon induction and action in transformed poikilothermic cells. The production and effect of interferon in the virus-transformed cell line TGk1, originating from kidney cells of Testudo gracea were studied and compared to those in the primary cell culture. West Nile virus and Newcastle disease virus were used as inducers. Interferon production in TGk1 cells began 6 hr later than in the primary cell culture and reached the maximum 64 IU, 18 hr after virus inoculation. In the primary culture, interferon production increased till the 48th hr reaching a fourfold level (256 IU). A significant reduction of the antiviral effect of interferon against vesicular stomatitis virus but not against vaccinia virus was observed in the transformed cells. The decreased interferon production and effect in TGk1 cells is regarded as a consequence of the disturbance of the interferon regulatory mechanism taking place as a result of the virus-induced transformation."} {"id": "PMID:168743", "title": "Concanavalin A as a quantitative and ultrastructural probe for normal and neoplastic cell surfaces.", "content": "Concanavalin A (Con A) has been popularly used as a cell surface probe for normal and neoplastic cells. Differences between normal fibroblasts and their transformed derivatives were examined using Con A agglutination, quantitative labeling with 125I-Con A and ultrastructural labeling with fluorescent- or ferritin-Con A. Con A agglutinates confluent-SV3T3 and 3T3 cells at midpoints of 20-60 and greater than, 500-2,000 mug/ml, respectively, and sparse cells at 5-15 and 1,200-1,500 mg/ml, respectively. Quantitative binding of 125I-Con A at 4 degrees C (10 or 15 min) with saturating lectin concentrations does not indicate a difference in the number of Con A receptors on sparse or confluent 3T3 and SV3T3 cells similar to many publications, but contrary to Noonan and Burger (1973). Under these conditions of labeling, ferritin-Con A is not internalized, indicating absence of endocytosis. The lateral mobility of Con A receptors and their relative ability to be aggregated on the cell surface by Con A was investigated with fluorescent- and ferritin-Con A. The initial distribution of Con A receptors on 3T3, SV3T3 and MSV3T3 cells under conditions of labeling at low temperature (0-5 degrees C) or to fixed cells was essentially randomly dispersed, but changes quickly to aggregated on SV3T3 and MSV3T3 (but not 3T3) after shifting the temperature to 20-37 degrees C, indicating, in general, a greater relative mobility of Con A receptors on SV3T3 and MSV3T3 cells. The aggregated Con A receptors seem to be directly involved in cell agglutination because they are usually found at the sites of cell-to-cell contact during 10 min agglutination experiments with ferritin-Con A. When confluent-3T3 cells are labeled on monolayer with ferritin-Con A at 0-4 degrees C, washed and then shifted to 20-37 degrees C for 10-15 min prior to in situ embedding, two classes of Con A receptors can be identified. One class appears to have low relative mobility and is associated with the 3T3 cell's extensive subplasma membrane microfilament network, while the other is capable of being aggregated and eventually endocytosed. On confluent-SV3T3 cells, only the latter class of receptors appears to be present, indicating a possible loss of cytoplasmic control over the distribution and mobility of lectin-binding sites on transformed cell surfaces.", "contents": "Concanavalin A as a quantitative and ultrastructural probe for normal and neoplastic cell surfaces. Concanavalin A (Con A) has been popularly used as a cell surface probe for normal and neoplastic cells. Differences between normal fibroblasts and their transformed derivatives were examined using Con A agglutination, quantitative labeling with 125I-Con A and ultrastructural labeling with fluorescent- or ferritin-Con A. Con A agglutinates confluent-SV3T3 and 3T3 cells at midpoints of 20-60 and greater than, 500-2,000 mug/ml, respectively, and sparse cells at 5-15 and 1,200-1,500 mg/ml, respectively. Quantitative binding of 125I-Con A at 4 degrees C (10 or 15 min) with saturating lectin concentrations does not indicate a difference in the number of Con A receptors on sparse or confluent 3T3 and SV3T3 cells similar to many publications, but contrary to Noonan and Burger (1973). Under these conditions of labeling, ferritin-Con A is not internalized, indicating absence of endocytosis. The lateral mobility of Con A receptors and their relative ability to be aggregated on the cell surface by Con A was investigated with fluorescent- and ferritin-Con A. The initial distribution of Con A receptors on 3T3, SV3T3 and MSV3T3 cells under conditions of labeling at low temperature (0-5 degrees C) or to fixed cells was essentially randomly dispersed, but changes quickly to aggregated on SV3T3 and MSV3T3 (but not 3T3) after shifting the temperature to 20-37 degrees C, indicating, in general, a greater relative mobility of Con A receptors on SV3T3 and MSV3T3 cells. The aggregated Con A receptors seem to be directly involved in cell agglutination because they are usually found at the sites of cell-to-cell contact during 10 min agglutination experiments with ferritin-Con A. When confluent-3T3 cells are labeled on monolayer with ferritin-Con A at 0-4 degrees C, washed and then shifted to 20-37 degrees C for 10-15 min prior to in situ embedding, two classes of Con A receptors can be identified. One class appears to have low relative mobility and is associated with the 3T3 cell's extensive subplasma membrane microfilament network, while the other is capable of being aggregated and eventually endocytosed. On confluent-SV3T3 cells, only the latter class of receptors appears to be present, indicating a possible loss of cytoplasmic control over the distribution and mobility of lectin-binding sites on transformed cell surfaces."} {"id": "PMID:168744", "title": "Cell cycle dependent agglutinability, distribution of concanavalin A binding sites and surface morphology of normal and transformed fibroblasts.", "content": "In studies on phenotypic reversion of transformed cells to normal growth patterns, we investigated the effect of dibutyryl cyclic AMP (dbc-AMP) and a protease inhibitor (TLCK) on growth of SV40-transformed mouse fibroblasts (3T3). The results did not support the hypothesis that transformed cells grown with dbc-AMP or TLCK are induced to contact-mediated growth control. The growth rate of SV-3T3 cells grown with the drugs was strongly reduced, due to accumulation of the cells in the G2 phase of the cell cycle. In addition, decreased agglutinability with concanavalin A (Con A) of those SV-3T3 cells was not caused by a direct effect of the drugs on the cell surface, but by partial synchronization of the cells in the G2 phase of the cycle. In synchronized cultures agglutinability of transformed cells reached a minimum in G2 and was maximal in mitosis and G1. Normal cells agglutinated only in mitosis. This suggested that agglutinability of cells is somehow cell cycle dependent. Cytochemical investigations on normal and transformed 3T3 cells had shown that Con A-induced redistribution of binding sites on the surface of these cells is not correlated with agglutinability. The present work on replicas confirmed this, but indicated also that normal 3T3 cells have more extended lamellipodia with less Con A binding sites than SV-3T3 cells. Preliminary scanning electron microscope data showed cell cycle dependent changes in 3T3 cells and also showed that confluent 3T3 and SV-3T3 cells suspended for agglutination tests had a different surface morphology. These results may represent additional factors important for differences in cell agglutinability by Con A.", "contents": "Cell cycle dependent agglutinability, distribution of concanavalin A binding sites and surface morphology of normal and transformed fibroblasts. In studies on phenotypic reversion of transformed cells to normal growth patterns, we investigated the effect of dibutyryl cyclic AMP (dbc-AMP) and a protease inhibitor (TLCK) on growth of SV40-transformed mouse fibroblasts (3T3). The results did not support the hypothesis that transformed cells grown with dbc-AMP or TLCK are induced to contact-mediated growth control. The growth rate of SV-3T3 cells grown with the drugs was strongly reduced, due to accumulation of the cells in the G2 phase of the cell cycle. In addition, decreased agglutinability with concanavalin A (Con A) of those SV-3T3 cells was not caused by a direct effect of the drugs on the cell surface, but by partial synchronization of the cells in the G2 phase of the cycle. In synchronized cultures agglutinability of transformed cells reached a minimum in G2 and was maximal in mitosis and G1. Normal cells agglutinated only in mitosis. This suggested that agglutinability of cells is somehow cell cycle dependent. Cytochemical investigations on normal and transformed 3T3 cells had shown that Con A-induced redistribution of binding sites on the surface of these cells is not correlated with agglutinability. The present work on replicas confirmed this, but indicated also that normal 3T3 cells have more extended lamellipodia with less Con A binding sites than SV-3T3 cells. Preliminary scanning electron microscope data showed cell cycle dependent changes in 3T3 cells and also showed that confluent 3T3 and SV-3T3 cells suspended for agglutination tests had a different surface morphology. These results may represent additional factors important for differences in cell agglutinability by Con A."} {"id": "PMID:168745", "title": "Concanavalin A as a probe for studying the mechanism of metabolic stimulation of leukocytes.", "content": "The disruption of the molecular organization of the plasma membrane of leukocytes by phagocytosable particles, or by agents such as surfactants, antibodies, phospholipase C, fatty acids and chemotactic factors, leads to a stimulation of the phagocyte oxidative metabolism. Concanavalin A (Con A) has been used as a tool to study the mechanism of this metabolic regulation. The binding of Con A to the surface of polymorphonuclear leukocytes (PMNL) or macrophages produces a rapid enhancement of oxygen uptake and glucose oxidation through the hexose monophosphate pathway (HMP). This is explained by an activation of the granular NADPH oxidase, the key enzyme in the metabolic stimulation. The effect of Con A is not due to endocytosed lectin, since Con A covalently coupled to large sepharose beads still acts as stimulant. The metabolic changes caused by Con A are reversible. If, after the onset of stimulation, sugars with high affinity for Con A are added to the leukocyte suspension, the activity of granular NADPH oxidase and the rate of respiration and glucose oxidation return to their resting values. The metabolic burst, while partially supressed by treatment of PMNL with iodoacetate, sodium flouride and cytochalasin B, is slightly increased by colchicine. Con A induces a selective release of granular enzymes (beta-glucuronidase, peroxidase, alkaline phosphatase) from PMNL, whereas no leakage of cytoplasmic enzymes is observed. The enzyme release is inhibited by iodoacetate and by drugs known to increase cell levels of cyclic AMP. Based on a current view of the mode of interaction between Con A and cell surfaces, a model of the metabolic disruption of leukocytes is presented.", "contents": "Concanavalin A as a probe for studying the mechanism of metabolic stimulation of leukocytes. The disruption of the molecular organization of the plasma membrane of leukocytes by phagocytosable particles, or by agents such as surfactants, antibodies, phospholipase C, fatty acids and chemotactic factors, leads to a stimulation of the phagocyte oxidative metabolism. Concanavalin A (Con A) has been used as a tool to study the mechanism of this metabolic regulation. The binding of Con A to the surface of polymorphonuclear leukocytes (PMNL) or macrophages produces a rapid enhancement of oxygen uptake and glucose oxidation through the hexose monophosphate pathway (HMP). This is explained by an activation of the granular NADPH oxidase, the key enzyme in the metabolic stimulation. The effect of Con A is not due to endocytosed lectin, since Con A covalently coupled to large sepharose beads still acts as stimulant. The metabolic changes caused by Con A are reversible. If, after the onset of stimulation, sugars with high affinity for Con A are added to the leukocyte suspension, the activity of granular NADPH oxidase and the rate of respiration and glucose oxidation return to their resting values. The metabolic burst, while partially supressed by treatment of PMNL with iodoacetate, sodium flouride and cytochalasin B, is slightly increased by colchicine. Con A induces a selective release of granular enzymes (beta-glucuronidase, peroxidase, alkaline phosphatase) from PMNL, whereas no leakage of cytoplasmic enzymes is observed. The enzyme release is inhibited by iodoacetate and by drugs known to increase cell levels of cyclic AMP. Based on a current view of the mode of interaction between Con A and cell surfaces, a model of the metabolic disruption of leukocytes is presented."} {"id": "PMID:168746", "title": "Enhanced cytotoxicity in mice of combinations of concanavalin A and selected antitumor drugs.", "content": "Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportioy 24 hr, the proportion of granulocytes had decreased to 56%. Adiministration of 5 mg Con A/kg 24 hr before 200 mg of 5[3,3-bis(2-chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simulatenous administration of 5 mg Con A/gm and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality per kg. In this regard, the lipid A-Con A complex had vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis.", "contents": "Enhanced cytotoxicity in mice of combinations of concanavalin A and selected antitumor drugs. Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportioy 24 hr, the proportion of granulocytes had decreased to 56%. Adiministration of 5 mg Con A/kg 24 hr before 200 mg of 5[3,3-bis(2-chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simulatenous administration of 5 mg Con A/gm and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality per kg. In this regard, the lipid A-Con A complex had vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis."} {"id": "PMID:168749", "title": "Studies on the spin state of 3-methylcholanthrene induced cytochrome P-450 from rat liver.", "content": "The time course of infuction of rat liver microsomal cytochrome P-450 by the polycyclic hydrocarbon 3-methylcholanthrene was followed by measuring the specific content of cytochrome P-450, benzpyrene hydroxylase activity, and the percent of cytochrome P-450 existing as the high-spin form (g equal to 7.9, 3.7 and 1.7) as determined by low temperature EPR spectroscopy. Significant increases in benzpyrene hydroxylase, cytochrome P-450 and high-spin ferric hemoprotein are seen twenty-four hours following 3-methylcholanthrene treatment. Administration of DL-ethionine prior to 3-methylcholanthrene treatment effectively blocks any increase in benzypyrene hydroxylase and cytochrome P-450 but not the increase in the levels of the high-spin species of the hemoprotein normally seen following 3-methylcholanthrene induction. In addition, partially purified cytochrome P-450 can be isolated from liver microsomes of 3-methylcholanthrene treated rats as low-spin ferric hemoprotein containing essentially no high-spin species (smaller than 1 per cent). This partially purified hemoprotein has the same substrate specificity as the microsomes from which it was derived. It is therefore concluded that the appearance of the high-spin form of cytochrome P-450, as quantitated by EPR, does not correlate with the induction of cytochrome P-450 and benezpyrene hydroxylase activity by 3-methylcholanthrene.", "contents": "Studies on the spin state of 3-methylcholanthrene induced cytochrome P-450 from rat liver. The time course of infuction of rat liver microsomal cytochrome P-450 by the polycyclic hydrocarbon 3-methylcholanthrene was followed by measuring the specific content of cytochrome P-450, benzpyrene hydroxylase activity, and the percent of cytochrome P-450 existing as the high-spin form (g equal to 7.9, 3.7 and 1.7) as determined by low temperature EPR spectroscopy. Significant increases in benzpyrene hydroxylase, cytochrome P-450 and high-spin ferric hemoprotein are seen twenty-four hours following 3-methylcholanthrene treatment. Administration of DL-ethionine prior to 3-methylcholanthrene treatment effectively blocks any increase in benzypyrene hydroxylase and cytochrome P-450 but not the increase in the levels of the high-spin species of the hemoprotein normally seen following 3-methylcholanthrene induction. In addition, partially purified cytochrome P-450 can be isolated from liver microsomes of 3-methylcholanthrene treated rats as low-spin ferric hemoprotein containing essentially no high-spin species (smaller than 1 per cent). This partially purified hemoprotein has the same substrate specificity as the microsomes from which it was derived. It is therefore concluded that the appearance of the high-spin form of cytochrome P-450, as quantitated by EPR, does not correlate with the induction of cytochrome P-450 and benezpyrene hydroxylase activity by 3-methylcholanthrene."} {"id": "PMID:168750", "title": "Biochemical characterization of highly purified cytochrome P-450 and other components of the mixed function oxidase system of liver microsomal membranes.", "content": "Cytochrome P-450 has been purified from liver microsomes of phenobarbital-induced rabbits in the presence of ionic and nonionic detergents to concentrations over 17 nmoles per mg of protein. The purified cytochrome P-450 LM gives a single major band on SDS-polyacrylamide gel electrophoresis representing about 90 per cent of the total protein. The polypeptide chain has a molecular weight of about 49,000 daltons. NADPH-cytochrome P-450 reductase has been purified from liver microsomes of phenobarbital-induced rats in the presence of ionic and nonionic detergents to a stage where it catalyzes the reduction of 33,000 nmoles of cytochrome c per min per mg of protein. The ratio of activities toward cytochrome P-450 and cytochrome c is constant throughout purification. The purified reductase contains equimolar amounts of FMN and FAD and gives a single major band on SDA-polyacrylamide gel electrophoresis accounting for about 70 per cent of the total protein; the molecular weight is about 80,000 daltons. The purified cytochrome P-450 is free of cytochrome b5 but contains another electron acceptor, provisionally called Factor C, which is equivalent in amount to the heme present. Two electrons are taken up per molecule of cytochrome P-450 from dithionite or from NADPH in the presence of catalytic amounts of the reductase, and both electrons are readily transferred from the reduced cytochrome P-450 to molecular oxygen or artificial electron acceptors. The reconstituted enzyme system containing purified cytochrome P-450, purified NADPH-cytochrome P-450 reductase, and phosphatidylcholine retains the ability to catalyze the hydroxylation of drugs, fatty acids, hydrocarbons, and aniline in the presence of NADPH and molecular oxygen.", "contents": "Biochemical characterization of highly purified cytochrome P-450 and other components of the mixed function oxidase system of liver microsomal membranes. Cytochrome P-450 has been purified from liver microsomes of phenobarbital-induced rabbits in the presence of ionic and nonionic detergents to concentrations over 17 nmoles per mg of protein. The purified cytochrome P-450 LM gives a single major band on SDS-polyacrylamide gel electrophoresis representing about 90 per cent of the total protein. The polypeptide chain has a molecular weight of about 49,000 daltons. NADPH-cytochrome P-450 reductase has been purified from liver microsomes of phenobarbital-induced rats in the presence of ionic and nonionic detergents to a stage where it catalyzes the reduction of 33,000 nmoles of cytochrome c per min per mg of protein. The ratio of activities toward cytochrome P-450 and cytochrome c is constant throughout purification. The purified reductase contains equimolar amounts of FMN and FAD and gives a single major band on SDA-polyacrylamide gel electrophoresis accounting for about 70 per cent of the total protein; the molecular weight is about 80,000 daltons. The purified cytochrome P-450 is free of cytochrome b5 but contains another electron acceptor, provisionally called Factor C, which is equivalent in amount to the heme present. Two electrons are taken up per molecule of cytochrome P-450 from dithionite or from NADPH in the presence of catalytic amounts of the reductase, and both electrons are readily transferred from the reduced cytochrome P-450 to molecular oxygen or artificial electron acceptors. The reconstituted enzyme system containing purified cytochrome P-450, purified NADPH-cytochrome P-450 reductase, and phosphatidylcholine retains the ability to catalyze the hydroxylation of drugs, fatty acids, hydrocarbons, and aniline in the presence of NADPH and molecular oxygen."} {"id": "PMID:168751", "title": "The role of cytochrome b5 in mixed function oxidations: effect of microsomal binding of the hemoprotein on hepatic N-demethylations.", "content": "Incubation of rat cytochrome b5 (D-b5) with rat liver microsomes resulted in specific binding of the hemoprotein. The bound hemoprotein was rapidly reduced by NADH. The NADH cytochrome c reductase activity in these preparations increased in proportion to the amount of cytochrome. In contrast to D-b5, which inhibited N-demethylation and the NADH synergism, the binding of cytochrome b5 preparations, reconstituted from heme and apocytochrome b5 had no effect on either the NADPH-dependent N-demethylation of aminopyrine or ethylmorphine or the NADH synergism observed with rat liver microsomes. In addition, manganese protoporphyrin-apocytochrome complex, when bound to microsomes in amounts equilvalent to D-b5, showed no effect on N-demethylation activity. These results suggest that homogeneous cytochrome b5 contains contaminating amounts of tightly bound detergent which presumably is removed during the extraction of the heme from the apocytochrome.", "contents": "The role of cytochrome b5 in mixed function oxidations: effect of microsomal binding of the hemoprotein on hepatic N-demethylations. Incubation of rat cytochrome b5 (D-b5) with rat liver microsomes resulted in specific binding of the hemoprotein. The bound hemoprotein was rapidly reduced by NADH. The NADH cytochrome c reductase activity in these preparations increased in proportion to the amount of cytochrome. In contrast to D-b5, which inhibited N-demethylation and the NADH synergism, the binding of cytochrome b5 preparations, reconstituted from heme and apocytochrome b5 had no effect on either the NADPH-dependent N-demethylation of aminopyrine or ethylmorphine or the NADH synergism observed with rat liver microsomes. In addition, manganese protoporphyrin-apocytochrome complex, when bound to microsomes in amounts equilvalent to D-b5, showed no effect on N-demethylation activity. These results suggest that homogeneous cytochrome b5 contains contaminating amounts of tightly bound detergent which presumably is removed during the extraction of the heme from the apocytochrome."} {"id": "PMID:168752", "title": "Electroresponsive properties of dendrites in central neurons.", "content": "A brief sketch of the historic development of the concept of neuronal integration is given. Some of the properties of dendritic spikes in chromatolyzed motoneurons, alligator Purkinje cells, and fish oculomotor neurons are reviewed, as well as the various ways in which the generation of dendritic spikes has altered our basic concept of neuronal integration. The principles of dendritic inhibition are elaborated, both as a \"tonic modulatory action\" and as a \"functional amputating system\" for dendrites that generate spikes.", "contents": "Electroresponsive properties of dendrites in central neurons. A brief sketch of the historic development of the concept of neuronal integration is given. Some of the properties of dendritic spikes in chromatolyzed motoneurons, alligator Purkinje cells, and fish oculomotor neurons are reviewed, as well as the various ways in which the generation of dendritic spikes has altered our basic concept of neuronal integration. The principles of dendritic inhibition are elaborated, both as a \"tonic modulatory action\" and as a \"functional amputating system\" for dendrites that generate spikes."} {"id": "PMID:168754", "title": "Some aspects of the electroanatomy of dendrites.", "content": "An understanding of the neuronal function requires the knowledge of the electroanatomy of dendrites, which comprise the major area and receive the main input in most neurons. Some simplifying assumptions are necessary to describe the electrical characteristics of the dendritic tree. The applicability of the simplified model of a combined equivalent dendritic cylinder proposed by Rall, was tested and verified by a combined analysis of anatomic and electrical data from the same spinal motoneurons. Assuming a uniform somadendritic membrane, estimates of the specific membrane resistance (RM: 2,700 +/- 920 omegacm2) were made by relating the neuronal input resistance with the combined dendritic trunk parameter (sigmaD3/2: 320 +/- 150-10(-6) CM3/2). From these combined anatomic and electrical data the dendritic electrotonic lengths (Lgeom: 1.5 +/- 0.3 times the length constant) were derived. Comparable L values (Ltrans: 1.5 +/- 0.3) resulted independently from analysis of membrane voltage transients during current steps. The linear dendritic cable model has proved its applicability for the analysis of small voltage deflections during current step applications at the soma as well as for the analysis of the majority of minimal postsynaptic potentials (PSP's). During the transmission along the dendritic cable the PSP undergoes changes in shape. These changes often permit a determination of the distance of the dendritic input from the soma. Unfortunately, the attenuation of the dendritic signal cannot be directly assessed. Dendritic synaptic transmission can be observed in isolation in chromatolytic motoneurons because the somal synapses are peeled off from the soma by proliferating glial cells in the course of retrograde reaction. These observations support the prediction that the PSP's with relatively short rise-times and duration originate from synapses near the soma. It may be questioned as to whether the linear dendritic cable approximation also applies to the larger voltage displacements during excitatory synaptic action. Particularly interesting is an increase of the apparent membrane resistance during depolarization known as anomalous rectification. The anomalous rectification could be reversibly eliminated and turned into a normal rectification by the application of cobalt ions or other calcium antagonists. Therefore, it appears likely that this phenomenon is caused by a voltage-(and time-) dependent reaction of the membrane, consisting of a smoothly increased calcium conductance during depolarizations that are even subthreshold for eliciting action potentials. Such a process would result in a shortening of the dendritic electrotonic length and in facilitating the postsynaptic excitatory transmission.", "contents": "Some aspects of the electroanatomy of dendrites. An understanding of the neuronal function requires the knowledge of the electroanatomy of dendrites, which comprise the major area and receive the main input in most neurons. Some simplifying assumptions are necessary to describe the electrical characteristics of the dendritic tree. The applicability of the simplified model of a combined equivalent dendritic cylinder proposed by Rall, was tested and verified by a combined analysis of anatomic and electrical data from the same spinal motoneurons. Assuming a uniform somadendritic membrane, estimates of the specific membrane resistance (RM: 2,700 +/- 920 omegacm2) were made by relating the neuronal input resistance with the combined dendritic trunk parameter (sigmaD3/2: 320 +/- 150-10(-6) CM3/2). From these combined anatomic and electrical data the dendritic electrotonic lengths (Lgeom: 1.5 +/- 0.3 times the length constant) were derived. Comparable L values (Ltrans: 1.5 +/- 0.3) resulted independently from analysis of membrane voltage transients during current steps. The linear dendritic cable model has proved its applicability for the analysis of small voltage deflections during current step applications at the soma as well as for the analysis of the majority of minimal postsynaptic potentials (PSP's). During the transmission along the dendritic cable the PSP undergoes changes in shape. These changes often permit a determination of the distance of the dendritic input from the soma. Unfortunately, the attenuation of the dendritic signal cannot be directly assessed. Dendritic synaptic transmission can be observed in isolation in chromatolytic motoneurons because the somal synapses are peeled off from the soma by proliferating glial cells in the course of retrograde reaction. These observations support the prediction that the PSP's with relatively short rise-times and duration originate from synapses near the soma. It may be questioned as to whether the linear dendritic cable approximation also applies to the larger voltage displacements during excitatory synaptic action. Particularly interesting is an increase of the apparent membrane resistance during depolarization known as anomalous rectification. The anomalous rectification could be reversibly eliminated and turned into a normal rectification by the application of cobalt ions or other calcium antagonists. Therefore, it appears likely that this phenomenon is caused by a voltage-(and time-) dependent reaction of the membrane, consisting of a smoothly increased calcium conductance during depolarizations that are even subthreshold for eliciting action potentials. Such a process would result in a shortening of the dendritic electrotonic length and in facilitating the postsynaptic excitatory transmission."} {"id": "PMID:168759", "title": "An office technique for identifying crystal in synovial fluid.", "content": "Crystal identification is made with a polarizing, color-compensated light microscope. Most microscopes can be easily and inexpensively adapted for crystal identification. The color compensator allows differentiation between the monosodium urate crystals of gout and the crystals of pseudogout, or calcium pyrophosphate deposition disease. All synovial fluid specimens should be examined. The observation of phagocytosis of crystals establishes that they are the etiologic agent responsible for an ongoing acute attack of arthritis.", "contents": "An office technique for identifying crystal in synovial fluid. Crystal identification is made with a polarizing, color-compensated light microscope. Most microscopes can be easily and inexpensively adapted for crystal identification. The color compensator allows differentiation between the monosodium urate crystals of gout and the crystals of pseudogout, or calcium pyrophosphate deposition disease. All synovial fluid specimens should be examined. The observation of phagocytosis of crystals establishes that they are the etiologic agent responsible for an ongoing acute attack of arthritis."} {"id": "PMID:168760", "title": "Nonbacterial thrombotic endocarditis in a Japanese autopsy sample. A review of eighty cases.", "content": "A study of nonbacterial thrombotic endocarditis has been carried out in a series of 3,404 autopsies performed upon atomic bomb survivors in Hiroshima in the period 1953-1970. The prevalence of the lesion was 2.4 per cent, with a greater frequency among the elderly and among females, and with a significant relationship to malignant neoplasms. In contrast to other reported series, there was a greater prevalence among cancers of the colon, rectum, and female genitourinary tract. No relationship was noted between the presence of NBTE and exposure to ionizing radiation. Histologic findings in the heart-valve leaflets in close proximity to the verrucae, like experimental studies reported by others, suggest that in association with severe systemic disease there appears a process consisting of degenerative changes in valve collagen and ground substance, with subsequent denudation of endothelium, localized almost entirely to the apposing leaflet surfaces of the left-heart valves. The verrucae of nonbacterial thrombotic endocarditis are then formed upon this abnormal leaflet surface. While the relationship between systemic disease and the pathologic changes observed in cardiac valve tissue is unclear, and although it is not known whether a \"hypercoagulable state\" may accentuate the tendency for thrombi to form upon these abnormal valves, there is no doubt that this lesion represents a clinically important complication of severe systemic disease. It also seems likely that in some cases NBTE may complicate an illness which may otherwise be curable. Increasing awareness of this pathologic entity among clinicians, coupled with appropriate laboratory techniques, most likely echocardiography, will permit more frequent diagnosis in living patients.", "contents": "Nonbacterial thrombotic endocarditis in a Japanese autopsy sample. A review of eighty cases. A study of nonbacterial thrombotic endocarditis has been carried out in a series of 3,404 autopsies performed upon atomic bomb survivors in Hiroshima in the period 1953-1970. The prevalence of the lesion was 2.4 per cent, with a greater frequency among the elderly and among females, and with a significant relationship to malignant neoplasms. In contrast to other reported series, there was a greater prevalence among cancers of the colon, rectum, and female genitourinary tract. No relationship was noted between the presence of NBTE and exposure to ionizing radiation. Histologic findings in the heart-valve leaflets in close proximity to the verrucae, like experimental studies reported by others, suggest that in association with severe systemic disease there appears a process consisting of degenerative changes in valve collagen and ground substance, with subsequent denudation of endothelium, localized almost entirely to the apposing leaflet surfaces of the left-heart valves. The verrucae of nonbacterial thrombotic endocarditis are then formed upon this abnormal leaflet surface. While the relationship between systemic disease and the pathologic changes observed in cardiac valve tissue is unclear, and although it is not known whether a \"hypercoagulable state\" may accentuate the tendency for thrombi to form upon these abnormal valves, there is no doubt that this lesion represents a clinically important complication of severe systemic disease. It also seems likely that in some cases NBTE may complicate an illness which may otherwise be curable. Increasing awareness of this pathologic entity among clinicians, coupled with appropriate laboratory techniques, most likely echocardiography, will permit more frequent diagnosis in living patients."} {"id": "PMID:168758", "title": "[Bronchial asthma and the beta adrenergic system].", "content": "The relationship between bronchial asthma and the beta adrenergic system is considered both from the physiopathologic and therapeutic point of view. A brief analysis of the sympathetic system is performed. The sympathetic nervous system is responsible for bronchodilation mediated through its beta-receptors. To evaluate this activity, beta adrenergic blockers such as propanolol are used. When this agent is administered, a descent of conductance is observed. On this condition, vagal stimulation brings about bronchoconstriction. At bronchial level, it seems that the beta-adrenergic system antagonizes vagal effect. From the physiopathologic point of view, Szentivanyi (1968) suggested a spontaneous beta block in the asthmatic. Other theories refer to a pathologic sensitivity of the peripheral bronchial receptors. The natural beta-adrenergics and the beta-adrenergic drugs enhance the synthesis of cAMP by stimulating the adenil cyclase system. This effect brings about relaxation of the bronchial smooth muscle. Considering the therapeutic effects, a comparative study of bronchodilators is performed. From all, Salbutamol has an intense broncholytic effect with little effect on heart dynamics. When sympathomimetics are bound to use in asthma, drugs such as Salbutamol and Terbutalina should be preferred because of its low cardiogenic effects. Its administration per os has rendered doubtful results.", "contents": "[Bronchial asthma and the beta adrenergic system]. The relationship between bronchial asthma and the beta adrenergic system is considered both from the physiopathologic and therapeutic point of view. A brief analysis of the sympathetic system is performed. The sympathetic nervous system is responsible for bronchodilation mediated through its beta-receptors. To evaluate this activity, beta adrenergic blockers such as propanolol are used. When this agent is administered, a descent of conductance is observed. On this condition, vagal stimulation brings about bronchoconstriction. At bronchial level, it seems that the beta-adrenergic system antagonizes vagal effect. From the physiopathologic point of view, Szentivanyi (1968) suggested a spontaneous beta block in the asthmatic. Other theories refer to a pathologic sensitivity of the peripheral bronchial receptors. The natural beta-adrenergics and the beta-adrenergic drugs enhance the synthesis of cAMP by stimulating the adenil cyclase system. This effect brings about relaxation of the bronchial smooth muscle. Considering the therapeutic effects, a comparative study of bronchodilators is performed. From all, Salbutamol has an intense broncholytic effect with little effect on heart dynamics. When sympathomimetics are bound to use in asthma, drugs such as Salbutamol and Terbutalina should be preferred because of its low cardiogenic effects. Its administration per os has rendered doubtful results."} {"id": "PMID:168761", "title": "Cyclic AMP induces ultrastructural differentiation of normal adult human adrenocortical cells cultured in vitro.", "content": "Electron microscopic studies have revealed that cyclic AMP, like ACTH, induces structural differentiation of adult human adreno-cortical cells cultured in vitro. These findings support the hypothesis that cyclic AMP can function as an intracellular mediator of the action of ACTH on the human adrenal gland.", "contents": "Cyclic AMP induces ultrastructural differentiation of normal adult human adrenocortical cells cultured in vitro. Electron microscopic studies have revealed that cyclic AMP, like ACTH, induces structural differentiation of adult human adreno-cortical cells cultured in vitro. These findings support the hypothesis that cyclic AMP can function as an intracellular mediator of the action of ACTH on the human adrenal gland."} {"id": "PMID:168762", "title": "The histogenesis of mixed cervical carcinomas. The concept of endocervical columnar-cell dysplasia.", "content": "In a case of cervical adenocarcinoma in situ, accompanied by relatively minor squamous-cell dysplasia, the neoplastic glandular cells were associated with \"abnormal\" but not clearly cancerous surface cells of the endocervix. Measurements of the nuclear DNA of these cells revealed an aneuploid pattern similar to that of epidermoid dysplasias. It is suggested that endocervical dysplasia is a valid entity and represents a step in the evolution of cervical adenocarcinoma from reserve cells comparable to the position of epidermoid dysplasia in the genesis of epidermoid carcinoma.", "contents": "The histogenesis of mixed cervical carcinomas. The concept of endocervical columnar-cell dysplasia. In a case of cervical adenocarcinoma in situ, accompanied by relatively minor squamous-cell dysplasia, the neoplastic glandular cells were associated with \"abnormal\" but not clearly cancerous surface cells of the endocervix. Measurements of the nuclear DNA of these cells revealed an aneuploid pattern similar to that of epidermoid dysplasias. It is suggested that endocervical dysplasia is a valid entity and represents a step in the evolution of cervical adenocarcinoma from reserve cells comparable to the position of epidermoid dysplasia in the genesis of epidermoid carcinoma."} {"id": "PMID:168763", "title": "Ultrastructural analysis of the testes in male pseudohermaphrodism reductase.", "content": "Light and electron microscopic observations of the testes in male pseudohermaphrodism due to deficiency of 17-ketosteroid reductase demonstrate an increased thickness of the walls of the seminiferous tubules. Although the seminiferous tubules are filled mostly by Sertoli cells containing crystalloids of Charcot-Bottcher, clusters of spermatogonia and spermatocytes are located at infrequent intervals along their lengths. Differentiation of spermatogenetic cells beyond the spermatocyte stage was not observed. Hyperplasia of Leydig cells, which are structurally similar to those of the normal testis, was pronounced. Pigment bodies were present in Leydig cells, whereas crystals of Reinke were not observed. The decreases in plasma androstenedione, testosterone and estrone following orchiectomy and the presence of a well-developed system of organelles (smooth endoplasmic reticulum and mitochondria containing tubular cristae), typical of steroid-secreting cells, indicate that the Leydig cells were active in steroid hormone synthesis, albeit deficient in 17-ketosteroid reductase activity.", "contents": "Ultrastructural analysis of the testes in male pseudohermaphrodism reductase. Light and electron microscopic observations of the testes in male pseudohermaphrodism due to deficiency of 17-ketosteroid reductase demonstrate an increased thickness of the walls of the seminiferous tubules. Although the seminiferous tubules are filled mostly by Sertoli cells containing crystalloids of Charcot-Bottcher, clusters of spermatogonia and spermatocytes are located at infrequent intervals along their lengths. Differentiation of spermatogenetic cells beyond the spermatocyte stage was not observed. Hyperplasia of Leydig cells, which are structurally similar to those of the normal testis, was pronounced. Pigment bodies were present in Leydig cells, whereas crystals of Reinke were not observed. The decreases in plasma androstenedione, testosterone and estrone following orchiectomy and the presence of a well-developed system of organelles (smooth endoplasmic reticulum and mitochondria containing tubular cristae), typical of steroid-secreting cells, indicate that the Leydig cells were active in steroid hormone synthesis, albeit deficient in 17-ketosteroid reductase activity."} {"id": "PMID:168764", "title": "Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly.", "content": "A girl had cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, absent tibiae, bowed fibulae, preaxial polydactyly of the feet, and abnormal dermal patterns at birth. She was born after a pregnancy complicated by exposure to multiple medications. This combination of malformations may represent a distinct entity unrelated to the medication or may be a complication of the intrauterine drug exposure.", "contents": "Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly. A girl had cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, absent tibiae, bowed fibulae, preaxial polydactyly of the feet, and abnormal dermal patterns at birth. She was born after a pregnancy complicated by exposure to multiple medications. This combination of malformations may represent a distinct entity unrelated to the medication or may be a complication of the intrauterine drug exposure."} {"id": "PMID:168766", "title": "The Seattle Virus Watch. VI. Observations of infections with and illness due to parainfluenza, mumps and respiratory syncytial viruses and Mycoplasma pneumoniae.", "content": "Seattle Virus Watch families were observed, 1965-1969, for infections with paramyxoviruses and M. pneumoniae by agent isolation and antibody assay of serial sera. Infection rates, based on serology, exceeded those in Tecumseh where families contained fewer young children. Rates per 100 person-years were 44.4 for parainfluenzavirus, 21.6 for respiratory syncytial (RS) virus and 12.3 for M. pneumoniae. Preschool children experienced the highest rates for RS and parainfluenza-viruses but, for the latter, rates were also high among older children and adults. Within invaded families infection rates generally varied inversely with age, although for M. pneumoniae the rates for adults and 6-9 year old children nearly equalled the infant rate. The introducers' identity and/or the age-specific infection rates in invaded families support the role of young schoolchildren in community spread of M. pneumoniae and, together with older children and adults, of RS virus. Young schoolchildren were less important than infants, preschoolers, and adults in spreading parainfluenza-viruses and less important than preschoolers and infants for mumps. The frequent infection of exposed older children and adults suggests that reinfection with all the agents studied is common. All agents spread significantly within families and secondary attack rates for the mostly non-immune infants indicated high infectivity of parainfluenza and mumps viruses. The basic high pathogenicity of these agents and of RS virus is indicated by the high frequency of illness among virus shedders (80-90%) and among seroconverting infants (greater than or equal 68%). The less frequent illness of older persons with serologically proven infection is consistent with diminished clinical response to reinfection. Parainfluenza-associated illnesses were relatively severe and contributed up to 9.3% to total respiratory illnesses. RS virus-related illnesses also were severe but contributed less (4-5%) to total respiratory disease. Mumps-associated illness was largely respiratory, 65% overall, 77% in infected infants and 75% above age 9. Thus, mumps virus emerges as another respiratory pathogen which is spread largely by 2-5-year old children rather than by schoolchildren with \"typical\" parotitis.", "contents": "The Seattle Virus Watch. VI. Observations of infections with and illness due to parainfluenza, mumps and respiratory syncytial viruses and Mycoplasma pneumoniae. Seattle Virus Watch families were observed, 1965-1969, for infections with paramyxoviruses and M. pneumoniae by agent isolation and antibody assay of serial sera. Infection rates, based on serology, exceeded those in Tecumseh where families contained fewer young children. Rates per 100 person-years were 44.4 for parainfluenzavirus, 21.6 for respiratory syncytial (RS) virus and 12.3 for M. pneumoniae. Preschool children experienced the highest rates for RS and parainfluenza-viruses but, for the latter, rates were also high among older children and adults. Within invaded families infection rates generally varied inversely with age, although for M. pneumoniae the rates for adults and 6-9 year old children nearly equalled the infant rate. The introducers' identity and/or the age-specific infection rates in invaded families support the role of young schoolchildren in community spread of M. pneumoniae and, together with older children and adults, of RS virus. Young schoolchildren were less important than infants, preschoolers, and adults in spreading parainfluenza-viruses and less important than preschoolers and infants for mumps. The frequent infection of exposed older children and adults suggests that reinfection with all the agents studied is common. All agents spread significantly within families and secondary attack rates for the mostly non-immune infants indicated high infectivity of parainfluenza and mumps viruses. The basic high pathogenicity of these agents and of RS virus is indicated by the high frequency of illness among virus shedders (80-90%) and among seroconverting infants (greater than or equal 68%). The less frequent illness of older persons with serologically proven infection is consistent with diminished clinical response to reinfection. Parainfluenza-associated illnesses were relatively severe and contributed up to 9.3% to total respiratory illnesses. RS virus-related illnesses also were severe but contributed less (4-5%) to total respiratory disease. Mumps-associated illness was largely respiratory, 65% overall, 77% in infected infants and 75% above age 9. Thus, mumps virus emerges as another respiratory pathogen which is spread largely by 2-5-year old children rather than by schoolchildren with \"typical\" parotitis."} {"id": "PMID:168767", "title": "Isolation of foamy viruses from baboon (Papio cynocephalus) tissues.", "content": "Fourty per cent of baboon kidney cell cultures were found to contain foamy virus contaminants regardless of sex of the animal, source or time of year. The older the animal, however, the higher the incidence. Fifty percent of placentas examined contained foamy virus, with first and second trimester specimens more likely to be positive. Foamy virus isolates from baboon lymphocytes were also more frequent as the age of the animal increased. Freezing and thawing these lymphocytes prevented foamy virus isolation. The foamy virus isolates were identified as types 1, 2, or 3.", "contents": "Isolation of foamy viruses from baboon (Papio cynocephalus) tissues. Fourty per cent of baboon kidney cell cultures were found to contain foamy virus contaminants regardless of sex of the animal, source or time of year. The older the animal, however, the higher the incidence. Fifty percent of placentas examined contained foamy virus, with first and second trimester specimens more likely to be positive. Foamy virus isolates from baboon lymphocytes were also more frequent as the age of the animal increased. Freezing and thawing these lymphocytes prevented foamy virus isolation. The foamy virus isolates were identified as types 1, 2, or 3."} {"id": "PMID:168768", "title": "Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype.", "content": "Univariate and bivariate analyses of cholesterol and triglycerides are performed after appropriate age adjustment on 247 individuals in 33 families where the probands have elevations of cholesterol, low density lipoprotein and triglycerides, and type IIb lipoprotein phenotype. Mixture of lognormal distributions are fitted by maximum likelihood to the data. Best fitting single and mixtures of lognormal distributions are compared with empirical cumulative plots, and the likelihood-ratio criterion is used to test for significance. A mixture of two lognormal distributions fits significantly better than one lognormal distribution for cholesterol but not for triglycerides. When a mixture of bivariate lognormals is fitted to the data, only one local maximum is found, suggesting action of a single genetic determinant in this sample. The best cutoff line is almost parallel to the triglyceride axis, indicating the relatively high involvement of cholesterol compared to triglycerides in separating the normal and abnormal groups. Using the best linear function, the difference in the two bivariate means is found to account for 61% of the total variation in log cholesterol and log triglycerides. To determine if the results are due to enrichment of the sample with familial hypercholesterolemia syndrome, seven families where the proband and/or any relative has tendon xanthomas are removed and the analyses repeated on the remaining 26 kindreds. The results of these analyses are virtually the same as those of the total sample. Also, a subsample of 21 families in which the proband and at least one additional kindred member are affected is analyzed in the same manner with similar results. For comparison, data from a study of families with combined hyperlipidemia [1] are analyzed in an analogous manner, bearing in mind that the populations sampled are probably different. Fitting a mixture of two bivariate distributions and finding the best cutoff to these data indicate that triglycerides are more involved in separating the two groups. Probably because of major differences in ascertainment, the distribution of lipid levels in oour patient group is practically indistinguishable from that of hypercholesterolemia, and the Seattle data [1] are more nearly similar to hypertriglyceridemia. It may be premature to consider familial combined hyperlipidemia as an entity distinct from both hypercholesterolemia and hypertriglyceridemia. We hope it will eventually be possible to analyze these data using a refined genetic model that includes both major gene and polygenic effects and to combine this form of analysis with quantitative tissue culture methods.", "contents": "Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype. Univariate and bivariate analyses of cholesterol and triglycerides are performed after appropriate age adjustment on 247 individuals in 33 families where the probands have elevations of cholesterol, low density lipoprotein and triglycerides, and type IIb lipoprotein phenotype. Mixture of lognormal distributions are fitted by maximum likelihood to the data. Best fitting single and mixtures of lognormal distributions are compared with empirical cumulative plots, and the likelihood-ratio criterion is used to test for significance. A mixture of two lognormal distributions fits significantly better than one lognormal distribution for cholesterol but not for triglycerides. When a mixture of bivariate lognormals is fitted to the data, only one local maximum is found, suggesting action of a single genetic determinant in this sample. The best cutoff line is almost parallel to the triglyceride axis, indicating the relatively high involvement of cholesterol compared to triglycerides in separating the normal and abnormal groups. Using the best linear function, the difference in the two bivariate means is found to account for 61% of the total variation in log cholesterol and log triglycerides. To determine if the results are due to enrichment of the sample with familial hypercholesterolemia syndrome, seven families where the proband and/or any relative has tendon xanthomas are removed and the analyses repeated on the remaining 26 kindreds. The results of these analyses are virtually the same as those of the total sample. Also, a subsample of 21 families in which the proband and at least one additional kindred member are affected is analyzed in the same manner with similar results. For comparison, data from a study of families with combined hyperlipidemia [1] are analyzed in an analogous manner, bearing in mind that the populations sampled are probably different. Fitting a mixture of two bivariate distributions and finding the best cutoff to these data indicate that triglycerides are more involved in separating the two groups. Probably because of major differences in ascertainment, the distribution of lipid levels in oour patient group is practically indistinguishable from that of hypercholesterolemia, and the Seattle data [1] are more nearly similar to hypertriglyceridemia. It may be premature to consider familial combined hyperlipidemia as an entity distinct from both hypercholesterolemia and hypertriglyceridemia. We hope it will eventually be possible to analyze these data using a refined genetic model that includes both major gene and polygenic effects and to combine this form of analysis with quantitative tissue culture methods."} {"id": "PMID:168769", "title": "Leukodystrophy, skin hyperpigmentation, and adrenal atrophy: Siemerling-Creutzfeldt disease. Transmission through several generations in two families.", "content": "Two apparently unrelated families with a history of leukodystrophy associated with adrenal insufficiency are presented. Only about 20 cases of this syndrome have been reported until now. It was first described by Siemerling and Creutzfeldt; therefore we propose the designation Siemerling-Creutzfeldt disease. Our pedigrees include 15 additional cases and prove that this disease is inherited as an X-linked or as an autosomal dominant trait with male sex limitation. Within these families, the interindividual variability of clinical signs is remarkable. Patients can survive into the fifth decade, and one has reproduced. Attempts to identify heterozygotes on the basis of endocrinologic investigations were unsuccessful.", "contents": "Leukodystrophy, skin hyperpigmentation, and adrenal atrophy: Siemerling-Creutzfeldt disease. Transmission through several generations in two families. Two apparently unrelated families with a history of leukodystrophy associated with adrenal insufficiency are presented. Only about 20 cases of this syndrome have been reported until now. It was first described by Siemerling and Creutzfeldt; therefore we propose the designation Siemerling-Creutzfeldt disease. Our pedigrees include 15 additional cases and prove that this disease is inherited as an X-linked or as an autosomal dominant trait with male sex limitation. Within these families, the interindividual variability of clinical signs is remarkable. Patients can survive into the fifth decade, and one has reproduced. Attempts to identify heterozygotes on the basis of endocrinologic investigations were unsuccessful."} {"id": "PMID:168771", "title": "Autoimmune hyperlipidemia in a patient. Atherosclerotic course and chaning immunoglobulin pattern during 21 years of study.", "content": "A 48 year old male patient presented with xanthomatosis, hyperbeta lipoproteinemia and hyper-IgA globulinemia; these two serum components occurred as a \"complex.\" The patient has subsequently been studied for 22 years (1952 to 1974). His serum cholesterol and triglyceride levels have been consistently and excessively high despite efforts to regulate them by means of diet or diet and drugs. Serum immunoglobulin A (IgA) concentration ranged from 1,400 to 3,400 mg/dl compared with a normal value of 156 plus or minus 92 mg/dl. The metabolism of lipoproteins, judged by vitamin A turnover studies was slow. Peripheral atherosclerosis became evident 15 years after beginning the study whereas cinecoronary arteriography concurrently demonstrated only minimum changes. Xanthomas exhibited marked regression only during the last 6 years, after 16 years of diet and the addition of clofibrate for 7 years. Beta lipoprotein and IgA globulin determined by immunofluorescent and immunoelectrophoretic technics were demonstrated in the atherosclerotic material obtained from the patient's arterial wall. They were also found in the plasma cells of the bone marrow. The IgA globulin-beta lipoprotein complex in the serum was broken with difficulty. The patient's isolated IgA globulin, free of lipoprotein, formed a firm complex when mixed with beta lipoprotein prepared from normal human serum. Initially, IgA globulin studies showed presence of both kappa and lambda light chains in normal proportion. But after 18 years, the IgA globulin has become monoclonal, type lambda. The plasma cells of the bone marrow have become progressively more atypical and immature. No clinical indications of multiple myeloma have been found. It is concluded that association of lipoproteins with IgA globulin in the serum of this patient with hyperlipidemia, hyper-IgA globulinemia did not prevent the development of atherosclerotic lesions and the deposition of lipids and lipoproteins in the plaques. It is possible that the lipoprotein-immunoglobulin association may have retarded the process, since it became manifest only after many years of known hyperlipidemia.", "contents": "Autoimmune hyperlipidemia in a patient. Atherosclerotic course and chaning immunoglobulin pattern during 21 years of study. A 48 year old male patient presented with xanthomatosis, hyperbeta lipoproteinemia and hyper-IgA globulinemia; these two serum components occurred as a \"complex.\" The patient has subsequently been studied for 22 years (1952 to 1974). His serum cholesterol and triglyceride levels have been consistently and excessively high despite efforts to regulate them by means of diet or diet and drugs. Serum immunoglobulin A (IgA) concentration ranged from 1,400 to 3,400 mg/dl compared with a normal value of 156 plus or minus 92 mg/dl. The metabolism of lipoproteins, judged by vitamin A turnover studies was slow. Peripheral atherosclerosis became evident 15 years after beginning the study whereas cinecoronary arteriography concurrently demonstrated only minimum changes. Xanthomas exhibited marked regression only during the last 6 years, after 16 years of diet and the addition of clofibrate for 7 years. Beta lipoprotein and IgA globulin determined by immunofluorescent and immunoelectrophoretic technics were demonstrated in the atherosclerotic material obtained from the patient's arterial wall. They were also found in the plasma cells of the bone marrow. The IgA globulin-beta lipoprotein complex in the serum was broken with difficulty. The patient's isolated IgA globulin, free of lipoprotein, formed a firm complex when mixed with beta lipoprotein prepared from normal human serum. Initially, IgA globulin studies showed presence of both kappa and lambda light chains in normal proportion. But after 18 years, the IgA globulin has become monoclonal, type lambda. The plasma cells of the bone marrow have become progressively more atypical and immature. No clinical indications of multiple myeloma have been found. It is concluded that association of lipoproteins with IgA globulin in the serum of this patient with hyperlipidemia, hyper-IgA globulinemia did not prevent the development of atherosclerotic lesions and the deposition of lipids and lipoproteins in the plaques. It is possible that the lipoprotein-immunoglobulin association may have retarded the process, since it became manifest only after many years of known hyperlipidemia."} {"id": "PMID:168772", "title": "Low density lipoprotein cholesterol (CLDL) and lipoprotein phenotyping.", "content": "Using an estimation of CLDL, 522 sera from 311 men and 211 women were studied. Lipoprotein phenotyping was done with and without knowledge of CLDL. Two hundred sixty-four of the 522 patients were considered abnormal without knowledge of CLDL. Interpretation was changed in 70 cases when CLDL was considered. Thirty-four were reclassified from 11B to IV because CLDL was not elevated. Thirty-three were reclassified from 11A to \"slightly elevated cholesterol without other evidence of hyperlipoproteinemia\" because CLDL was not elevated. Three were reclassified from normal to 11A because of elevated CLDL associated with borderline normal cholesterol.", "contents": "Low density lipoprotein cholesterol (CLDL) and lipoprotein phenotyping. Using an estimation of CLDL, 522 sera from 311 men and 211 women were studied. Lipoprotein phenotyping was done with and without knowledge of CLDL. Two hundred sixty-four of the 522 patients were considered abnormal without knowledge of CLDL. Interpretation was changed in 70 cases when CLDL was considered. Thirty-four were reclassified from 11B to IV because CLDL was not elevated. Thirty-three were reclassified from 11A to \"slightly elevated cholesterol without other evidence of hyperlipoproteinemia\" because CLDL was not elevated. Three were reclassified from normal to 11A because of elevated CLDL associated with borderline normal cholesterol."} {"id": "PMID:168774", "title": "Conjugated estrogens and hypercoagulability.", "content": "A group of 11 menopausal women receiving 1.25 mg. of conjugated estrogens daily had coagulation tests to determine the development of hypercoagulability after taking 5 and 21 tablets. There was no essential change in thrombin generation or fibrinolytic activity as measured by euglobin lysis time. There was a shift toward hypercoagulability in all three parameters of the thrombelastograms. The decrease of the antithrombin III activity was not as pronounced following the administration of conjugated estrogens as had been the change associated with oral contraceptives. Fibrin monomers were observed in some women during the first week of Premarin therapy.", "contents": "Conjugated estrogens and hypercoagulability. A group of 11 menopausal women receiving 1.25 mg. of conjugated estrogens daily had coagulation tests to determine the development of hypercoagulability after taking 5 and 21 tablets. There was no essential change in thrombin generation or fibrinolytic activity as measured by euglobin lysis time. There was a shift toward hypercoagulability in all three parameters of the thrombelastograms. The decrease of the antithrombin III activity was not as pronounced following the administration of conjugated estrogens as had been the change associated with oral contraceptives. Fibrin monomers were observed in some women during the first week of Premarin therapy."} {"id": "PMID:168776", "title": "Cryptophthalmos syndrome with basal encephaloceles.", "content": "A 2,144-g white girl was born with absence of the right ear and eye, cleft lip and palate, two basal encephaloceles, tricuspid atresia, ventricualr and atrial septal defects, detransposition of the great vessels, right aortic arch, and aberrant right subclavian artery. Through an oval defect in the center of the sphenoid bone, soft tissue protruded into the right nasopharynx. The medial portions of the roof of both orbits and the cribriform plate were absent and soft tissue protruded through this bony defect. Basal tomography was required to demonstrate the encephaloceles, which should be suspected in any child with a median cleft syndrome, a flat broad nasal root, and hypertelorism.", "contents": "Cryptophthalmos syndrome with basal encephaloceles. A 2,144-g white girl was born with absence of the right ear and eye, cleft lip and palate, two basal encephaloceles, tricuspid atresia, ventricualr and atrial septal defects, detransposition of the great vessels, right aortic arch, and aberrant right subclavian artery. Through an oval defect in the center of the sphenoid bone, soft tissue protruded into the right nasopharynx. The medial portions of the roof of both orbits and the cribriform plate were absent and soft tissue protruded through this bony defect. Basal tomography was required to demonstrate the encephaloceles, which should be suspected in any child with a median cleft syndrome, a flat broad nasal root, and hypertelorism."} {"id": "PMID:168773", "title": "Diabetic hypertriglyceridemia.", "content": "The conference opened with the clinical presentation of a 50-year-old male with fasting hyperglycemia (296 mg per cent) and hypertriglyceridemia (2736 mg per cent). The discussion began with a summary of current concepts regarding the manner in which chylomicra (intestine) and very low density lipoproteins (intestine and liver) are formed, transported into the plasma, and removed from the circulation. This was followed by a consideration of diabetic hypertriglyceridemia in which this syndrome was subdivided into two categories. The first form is seen in patients with severe fasting hyperglycemia, and is characterized by marked insulin deficiency, decreased very low density lipoprotein production, a fall in the activity of lipoprotein lipase, and hypertriglyceridemia secondary to a defect in removal of lipoproteins from the plasma. In contrast the other form of diabetic hypertriglyceridemia is seen in patients with minimal abnormalities of carbohydrate tolerance, and in this instance insulin resistance, not insulin lack, seems to play the pivotal role. In these patients, the rise in plasma triglyceride levels seems to be secondary to increased production of very low density lipoproteins, presumably as a result of the hyperinsulinemia associated with the insulin resistance. The conference ended with an attempt to relate the patient presented to the models of diabetic hypertriglyceridemia that had been defined.", "contents": "Diabetic hypertriglyceridemia. The conference opened with the clinical presentation of a 50-year-old male with fasting hyperglycemia (296 mg per cent) and hypertriglyceridemia (2736 mg per cent). The discussion began with a summary of current concepts regarding the manner in which chylomicra (intestine) and very low density lipoproteins (intestine and liver) are formed, transported into the plasma, and removed from the circulation. This was followed by a consideration of diabetic hypertriglyceridemia in which this syndrome was subdivided into two categories. The first form is seen in patients with severe fasting hyperglycemia, and is characterized by marked insulin deficiency, decreased very low density lipoprotein production, a fall in the activity of lipoprotein lipase, and hypertriglyceridemia secondary to a defect in removal of lipoproteins from the plasma. In contrast the other form of diabetic hypertriglyceridemia is seen in patients with minimal abnormalities of carbohydrate tolerance, and in this instance insulin resistance, not insulin lack, seems to play the pivotal role. In these patients, the rise in plasma triglyceride levels seems to be secondary to increased production of very low density lipoproteins, presumably as a result of the hyperinsulinemia associated with the insulin resistance. The conference ended with an attempt to relate the patient presented to the models of diabetic hypertriglyceridemia that had been defined."} {"id": "PMID:168777", "title": "Epidemic hemorrhagic keratoconjunctivitis.", "content": "A new type of acute keratoconjunctivitis developed throughout Southeast Asia, beginning in Singapore in the summer of 1970. It was highly contagious and probably was transmitted from person to person by the hand to eye route. Sixteen cases, diagnosed by viral isolation or serologic study, or both, were subjected to detailed clinical observation. The characteristic features included a short incubation period of one or two days, watery or serous discharge, subconjunctival hemorrhage, and pinpoint superficial keratopathy. The disease usually resolved rapidly within one to two weeks without sequelae.", "contents": "Epidemic hemorrhagic keratoconjunctivitis. A new type of acute keratoconjunctivitis developed throughout Southeast Asia, beginning in Singapore in the summer of 1970. It was highly contagious and probably was transmitted from person to person by the hand to eye route. Sixteen cases, diagnosed by viral isolation or serologic study, or both, were subjected to detailed clinical observation. The characteristic features included a short incubation period of one or two days, watery or serous discharge, subconjunctival hemorrhage, and pinpoint superficial keratopathy. The disease usually resolved rapidly within one to two weeks without sequelae."} {"id": "PMID:168778", "title": "Mammary and extramammary Paget's disease. An immunocytochemical study.", "content": "The localization and distribution of human casein has been investigated in 20 patients with Paget's disease (16 with the mammary and 4 with the extramammary form) by means of immunofluorescence and immunoperoxidase techniques. This milk protein has been detected in neoplastic cells in intraductal carcinomas of the nipple and in intraepidermal cells identifiable as Paget cells. The degree of the staining varied in different cells of the same case and in different cases. Some casein-containing intraepidermal cells, as revealed by immunofluorescence, could not be recognized after retaining of the sections as Paget cells: they could not morphologically be distinguished from other basally located epidermal cells. This finding raises the question of the existence of \"pre-Paget\" cells. The results obtained are discussed in relation to theories on the origin and nature of Paget cells. The immunocytochemical methods for casein detection might also be find possible application in the diagnosis of Paget's disease.", "contents": "Mammary and extramammary Paget's disease. An immunocytochemical study. The localization and distribution of human casein has been investigated in 20 patients with Paget's disease (16 with the mammary and 4 with the extramammary form) by means of immunofluorescence and immunoperoxidase techniques. This milk protein has been detected in neoplastic cells in intraductal carcinomas of the nipple and in intraepidermal cells identifiable as Paget cells. The degree of the staining varied in different cells of the same case and in different cases. Some casein-containing intraepidermal cells, as revealed by immunofluorescence, could not be recognized after retaining of the sections as Paget cells: they could not morphologically be distinguished from other basally located epidermal cells. This finding raises the question of the existence of \"pre-Paget\" cells. The results obtained are discussed in relation to theories on the origin and nature of Paget cells. The immunocytochemical methods for casein detection might also be find possible application in the diagnosis of Paget's disease."} {"id": "PMID:168779", "title": "Production of lymphokine-like factors (cytokines) by simian virus 40-infected and simian virus 40-transformed cells.", "content": "Macrophage migration inhibitory (MIF-like) activity was demonstrated in the supernatant fluids from primary cultures of African green monkey kidney cells infected with simian virus 40 (SV 40) virus. Kidney cell cultures not infected by virus had no MIF activity. Supernatant fluids from continuous cultures of nontransformed and SV 40-transformed human fibroblasts contained MIF-like activity. Productive infection with SV 40 virus results in the production of a lymphokine-like factor, as previously observed in other virus-cell systems, involving mumps virus and Newcast,le disease virus. However, while infection with these paramyxoviruses causes the production of macrophage and neutrophil chemotactic agents as well as an MIF, SV 40 infection does not induce chemotactic factors. The results reported here, taken in conjunction with previous observations by ourselves and others, suggest that the production of lymphokine-like factors (cytokines) may represent a general biologic phenomenon, and that many, if not all, cell types, when appropriately stimulated, may be capable of such activity.", "contents": "Production of lymphokine-like factors (cytokines) by simian virus 40-infected and simian virus 40-transformed cells. Macrophage migration inhibitory (MIF-like) activity was demonstrated in the supernatant fluids from primary cultures of African green monkey kidney cells infected with simian virus 40 (SV 40) virus. Kidney cell cultures not infected by virus had no MIF activity. Supernatant fluids from continuous cultures of nontransformed and SV 40-transformed human fibroblasts contained MIF-like activity. Productive infection with SV 40 virus results in the production of a lymphokine-like factor, as previously observed in other virus-cell systems, involving mumps virus and Newcast,le disease virus. However, while infection with these paramyxoviruses causes the production of macrophage and neutrophil chemotactic agents as well as an MIF, SV 40 infection does not induce chemotactic factors. The results reported here, taken in conjunction with previous observations by ourselves and others, suggest that the production of lymphokine-like factors (cytokines) may represent a general biologic phenomenon, and that many, if not all, cell types, when appropriately stimulated, may be capable of such activity."} {"id": "PMID:168780", "title": "Separation of cells with histochemically demonstrable acid phosphatase activity from suspensions of human prostatic cells in an isokinetic gradient of Ficoll in tissue culture medium.", "content": "Collagenase, trypsin, and pronase were used in separate, parallel experiments to obtain cell suspensions from human prostates obtained from surgical resections and autopsies. All of the examined prostates demonstrated benign hyperplasia. The dissociation using pronase gave both the largest number of nucleated cells and the largest proportion of viable cells from prostates. Surgically resected prostates gave a larger number of cells per gram of tissue than prostates obtained from autopsy. Cells obtained from surgically resected prostates were separated both by isopycnic sedimentation and by velocity sedimentation in a previously described isokinetic gradient. We studied fifteen prostates obtained at surgery; using pronase, we obtained 2.1 plus or minus 3.5 times 10(6) cells/g. Of these cells, 34.0 plus or minus 14.7% contained histochemically demonstrable acid phosphatase. Cells from six prostates were separated by velocity sedimentation in the isokinetic gradients; in the purest fractions from the isokinetic gradients, 81.0 plus or minus 12.2% of nucleated cells had histochemically demonstrable acid phosphatase. The cells in the purest fractions appeared to be epithelial cells. More than 99% of these separated cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying epithelial cells from human prostates.", "contents": "Separation of cells with histochemically demonstrable acid phosphatase activity from suspensions of human prostatic cells in an isokinetic gradient of Ficoll in tissue culture medium. Collagenase, trypsin, and pronase were used in separate, parallel experiments to obtain cell suspensions from human prostates obtained from surgical resections and autopsies. All of the examined prostates demonstrated benign hyperplasia. The dissociation using pronase gave both the largest number of nucleated cells and the largest proportion of viable cells from prostates. Surgically resected prostates gave a larger number of cells per gram of tissue than prostates obtained from autopsy. Cells obtained from surgically resected prostates were separated both by isopycnic sedimentation and by velocity sedimentation in a previously described isokinetic gradient. We studied fifteen prostates obtained at surgery; using pronase, we obtained 2.1 plus or minus 3.5 times 10(6) cells/g. Of these cells, 34.0 plus or minus 14.7% contained histochemically demonstrable acid phosphatase. Cells from six prostates were separated by velocity sedimentation in the isokinetic gradients; in the purest fractions from the isokinetic gradients, 81.0 plus or minus 12.2% of nucleated cells had histochemically demonstrable acid phosphatase. The cells in the purest fractions appeared to be epithelial cells. More than 99% of these separated cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying epithelial cells from human prostates."} {"id": "PMID:168781", "title": "Norepinephrine vascoconstrictor escape in isolated meseneric arteries.", "content": "When isolated superfused cat mesentric arterial rings were exposed to norepinephrine(NE) 10'-6 g/ml, force initially increased but subsequently declined despite continuedadministration of NE. Phasic contractions occurred in 48% of the vessels. Norepinephrine concentrations just above threshold induced tonic contractions without escape. When NE was administered after brief exposure of the arterial rings to low-calcium solutions, peak force development and escape were both reduced and phasic contractions were abolished. Escape did not occur in potassium-depolarized vessels. The peak response was increased and escape was reduced by substituting sodium in the Krebs solution by lithium and by substituting chloride with iodide or perchlorate. Substitution of chloride by isethionate reduced the peak NE resonse and abolished escape. Propanolol was without effect. It is suggested that escape from NE vasoconstriction in mesenteric arteries is due to fading of propagated activity.", "contents": "Norepinephrine vascoconstrictor escape in isolated meseneric arteries. When isolated superfused cat mesentric arterial rings were exposed to norepinephrine(NE) 10'-6 g/ml, force initially increased but subsequently declined despite continuedadministration of NE. Phasic contractions occurred in 48% of the vessels. Norepinephrine concentrations just above threshold induced tonic contractions without escape. When NE was administered after brief exposure of the arterial rings to low-calcium solutions, peak force development and escape were both reduced and phasic contractions were abolished. Escape did not occur in potassium-depolarized vessels. The peak response was increased and escape was reduced by substituting sodium in the Krebs solution by lithium and by substituting chloride with iodide or perchlorate. Substitution of chloride by isethionate reduced the peak NE resonse and abolished escape. Propanolol was without effect. It is suggested that escape from NE vasoconstriction in mesenteric arteries is due to fading of propagated activity."} {"id": "PMID:168782", "title": "Effect of intravenous infusion of corticosteroids on blood pressure, electrolytes, and water metabolism in sheep.", "content": "ACTH administration (80 IU/day for 5 days), which produces hypertension and charateristic metabolic effects in sheep (38), has been compared with the effect of intravenous infusion of cortisol (5 mg/h), corticosterone (0.5 mg/h), deoxycorticosterone (50 mug/h), and 11-deoxycortisol (1 mg/h), each given singly for 5 days. Further, a mixture consisting of aldosterone (3 mug/h), cortisol (5 mg/h), deoxycorticosterone (25 mug/h), corticosterone (0.5 mg/h), and 11-deoxycortisol (1 mg/h), was also infused intravenously for 5 days. In another series of experiments, 18-hydroxydeoxycorticosterone (100 mg/h) was also included in the combined-steroid solution. With the exception of 18-hydroxydeoxycorticosterone, which was not measured, the rates of infusionproduced peripheral arterial blood levels of the steroids similiar to those seen with ACTH stimulation. Blood pressure,water intake, urine output, and plasma and urinary electrolytes were measured: individual steroids had little effect on these, but manyof the metabolic changes produced by ATCH (hypokalemia and increased water intake andurine output) were produced by the combined-steroid infusion. However, the combined-steroid infusion failed to induce an increase in blood pressure similiar to that seen inthe ACTH experiments. Thus the findings are against a major role in ACTH hypertension for any steroid used, either singly or in combination. As yet unrecgnized factor/s may be involved in the ACTH-induced hypertension.", "contents": "Effect of intravenous infusion of corticosteroids on blood pressure, electrolytes, and water metabolism in sheep. ACTH administration (80 IU/day for 5 days), which produces hypertension and charateristic metabolic effects in sheep (38), has been compared with the effect of intravenous infusion of cortisol (5 mg/h), corticosterone (0.5 mg/h), deoxycorticosterone (50 mug/h), and 11-deoxycortisol (1 mg/h), each given singly for 5 days. Further, a mixture consisting of aldosterone (3 mug/h), cortisol (5 mg/h), deoxycorticosterone (25 mug/h), corticosterone (0.5 mg/h), and 11-deoxycortisol (1 mg/h), was also infused intravenously for 5 days. In another series of experiments, 18-hydroxydeoxycorticosterone (100 mg/h) was also included in the combined-steroid solution. With the exception of 18-hydroxydeoxycorticosterone, which was not measured, the rates of infusionproduced peripheral arterial blood levels of the steroids similiar to those seen with ACTH stimulation. Blood pressure,water intake, urine output, and plasma and urinary electrolytes were measured: individual steroids had little effect on these, but manyof the metabolic changes produced by ATCH (hypokalemia and increased water intake andurine output) were produced by the combined-steroid infusion. However, the combined-steroid infusion failed to induce an increase in blood pressure similiar to that seen inthe ACTH experiments. Thus the findings are against a major role in ACTH hypertension for any steroid used, either singly or in combination. As yet unrecgnized factor/s may be involved in the ACTH-induced hypertension."} {"id": "PMID:168783", "title": "Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum.", "content": "Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.", "contents": "Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum. Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process."} {"id": "PMID:168784", "title": "Insulin and epinephrine effects on heart glycogen synthase and phosphorylase activity.", "content": "The effect of intravenous epinephrine on heart glycogen synthase and phosphorylase systems in control and insulin-pretreated rats was studied. The percent of synthase in the I form decreased rapidly after epinephrine treatment but the change was small and sometimes not significant. In insulin-pretreated rats in which the percent synthase I was increased, epinephrine produced a definate and highly significant decrease. There was a simultaneous increase in percent phosphorylase a in both groups. The synthase and phosphorylase responses were statiscally significant at 2.5 mug epinephrine/kgor more. These data are compatible with a mechanism in which protein kinase is activated by an increased cAMP concentration and affects both the synthase and phosphorylasesystems simultaneously. Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a. Although insulin had little effect on the response ofthe synthase and phosphorylase systems to epinephrine, it nealry completely blocked glycogen degradation. The mechanism is unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vivo. Acetylcholine had no effect on synthase I, phosphorylase a, or cAMP in control or in insulin-pretreated animals.", "contents": "Insulin and epinephrine effects on heart glycogen synthase and phosphorylase activity. The effect of intravenous epinephrine on heart glycogen synthase and phosphorylase systems in control and insulin-pretreated rats was studied. The percent of synthase in the I form decreased rapidly after epinephrine treatment but the change was small and sometimes not significant. In insulin-pretreated rats in which the percent synthase I was increased, epinephrine produced a definate and highly significant decrease. There was a simultaneous increase in percent phosphorylase a in both groups. The synthase and phosphorylase responses were statiscally significant at 2.5 mug epinephrine/kgor more. These data are compatible with a mechanism in which protein kinase is activated by an increased cAMP concentration and affects both the synthase and phosphorylasesystems simultaneously. Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a. Although insulin had little effect on the response ofthe synthase and phosphorylase systems to epinephrine, it nealry completely blocked glycogen degradation. The mechanism is unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vivo. Acetylcholine had no effect on synthase I, phosphorylase a, or cAMP in control or in insulin-pretreated animals."} {"id": "PMID:168785", "title": "Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances.", "content": "A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.", "contents": "Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances. A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity."} {"id": "PMID:168786", "title": "CNS regulation of metabolic rate in the kangaroo rat Dipodomys ingens.", "content": "Water-perfused thermodes were chronically implanted around the preoptic nuclei and hypothalamus (POH) of kangaroo rats (Dipodomys ingens). Responses in rate of metabolic heat production to manipulations of POH temperature (Thy) were measured in unanesthetized, unrestrained animals at ambient temperatures of 10, 20, 25, and 30 degreeC. The threshold Thy and the proportionally constant (alpha) for this response consistently decreased as ambient temperature increased, but alpha was not significantly different between any two Ta's. Average values of alpha for the three animals studied ranged between -.0024 W.g minus 1.degree C minus 1 and -.0034 W.g minus1.degree C minus 1. No influence of extrahypothalamic core temperature on the characteristics of the central nervous system regulatory mechanism was observed. Ahypothesis accounting for high POH and low peripheral thermosensitivities in small mammals is presented. An additional finding was that during sleep there is a profound depression or elimination of POH thermosensitivity in this species.", "contents": "CNS regulation of metabolic rate in the kangaroo rat Dipodomys ingens. Water-perfused thermodes were chronically implanted around the preoptic nuclei and hypothalamus (POH) of kangaroo rats (Dipodomys ingens). Responses in rate of metabolic heat production to manipulations of POH temperature (Thy) were measured in unanesthetized, unrestrained animals at ambient temperatures of 10, 20, 25, and 30 degreeC. The threshold Thy and the proportionally constant (alpha) for this response consistently decreased as ambient temperature increased, but alpha was not significantly different between any two Ta's. Average values of alpha for the three animals studied ranged between -.0024 W.g minus 1.degree C minus 1 and -.0034 W.g minus1.degree C minus 1. No influence of extrahypothalamic core temperature on the characteristics of the central nervous system regulatory mechanism was observed. Ahypothesis accounting for high POH and low peripheral thermosensitivities in small mammals is presented. An additional finding was that during sleep there is a profound depression or elimination of POH thermosensitivity in this species."} {"id": "PMID:168787", "title": "Relationship between adenosine concentration and oxygen supply in rat brain.", "content": "Since adenosine is present in normal brain tissue and cerebrosipinal fluid and since it dilates the pial vessels, it is possible that adenosine, in addition to H-+, is also a mediator of the metabolic regulation of cerebral blood flow. Evidence supporting this hypothesis was obtained under various experimental conditions characterized by achange in brain oxygen supply. The brain was frozen in situ by means of a small bonerongeur precooled in liquid N2 and the tissue was processed for adenosine determination (nmol/g of tissue). Electrical stimulation of the cortex at 0, 15, 30, and 45 Hz yielded adenosine levels of 5.4 plus or minus 0.7, 10.5 plus or minus 1.7, 13.0 plusor minus 1.2, and 9.0 plus or minus 2.1 nmol/g. Arterial pressures of 87, 60, and 40mmHg gave adenosine levels of 7.5 plus or minus 0.76, 13 plus or minus 2.6, and 26.6plus or minus 3.3, respectively. Ventilation with 29.7, 20, 10.7, and5.5% O2 significantly increased the adenosine levels to 9.4 plus or minus 3.0, 6.4 plus or minus 1.2, 30.0 plus or minus 9.3, and 63.3 plus or minus 18.2 nmol/g, respectively. Hyperventilation significantly increased adenosine form 6.7 plus or minus 1.0 to 11.8 plus or minus 1.4 nmol/g. This increased adenosine level was reduced by additionof CO2 to the ventilating gas mixture. Lactate, the main H-+ donor, pyruvate, and cAMP changed in a fashion parallel to adenosine. However, cAMP showedonly a small increase in adenosine. These findings are in accordance with the concept that adenosine and H-+ may act synergistally to regulate cerebral blood flow and that endogenous adenosine may exert a small effect on cAMP formation.", "contents": "Relationship between adenosine concentration and oxygen supply in rat brain. Since adenosine is present in normal brain tissue and cerebrosipinal fluid and since it dilates the pial vessels, it is possible that adenosine, in addition to H-+, is also a mediator of the metabolic regulation of cerebral blood flow. Evidence supporting this hypothesis was obtained under various experimental conditions characterized by achange in brain oxygen supply. The brain was frozen in situ by means of a small bonerongeur precooled in liquid N2 and the tissue was processed for adenosine determination (nmol/g of tissue). Electrical stimulation of the cortex at 0, 15, 30, and 45 Hz yielded adenosine levels of 5.4 plus or minus 0.7, 10.5 plus or minus 1.7, 13.0 plusor minus 1.2, and 9.0 plus or minus 2.1 nmol/g. Arterial pressures of 87, 60, and 40mmHg gave adenosine levels of 7.5 plus or minus 0.76, 13 plus or minus 2.6, and 26.6plus or minus 3.3, respectively. Ventilation with 29.7, 20, 10.7, and5.5% O2 significantly increased the adenosine levels to 9.4 plus or minus 3.0, 6.4 plus or minus 1.2, 30.0 plus or minus 9.3, and 63.3 plus or minus 18.2 nmol/g, respectively. Hyperventilation significantly increased adenosine form 6.7 plus or minus 1.0 to 11.8 plus or minus 1.4 nmol/g. This increased adenosine level was reduced by additionof CO2 to the ventilating gas mixture. Lactate, the main H-+ donor, pyruvate, and cAMP changed in a fashion parallel to adenosine. However, cAMP showedonly a small increase in adenosine. These findings are in accordance with the concept that adenosine and H-+ may act synergistally to regulate cerebral blood flow and that endogenous adenosine may exert a small effect on cAMP formation."} {"id": "PMID:168788", "title": "The cost of schizophrenia.", "content": "The cost of schizophrenia has been estimated at $11.6 to $19.5 billion annually. About two-thirds of this cost is due to lack of productivity by schizophrenic patients and about one-fifth to treatment costs. The estimate might be considerably higher if better figures were available on the cost of maintaining patients in the community. In the absence of more effective treatment, the savings from the current trend toward shorter hospitalization cannot be expected to decrease-and may actually increase-the overall costs of schizophrenia to society. The authors make recommendations aimed at reducing the cost by helping schizophrenic patients to be more productive through a system of community alternative-care facilities, increased rehabilitation services, aftercare, and research.", "contents": "The cost of schizophrenia. The cost of schizophrenia has been estimated at $11.6 to $19.5 billion annually. About two-thirds of this cost is due to lack of productivity by schizophrenic patients and about one-fifth to treatment costs. The estimate might be considerably higher if better figures were available on the cost of maintaining patients in the community. In the absence of more effective treatment, the savings from the current trend toward shorter hospitalization cannot be expected to decrease-and may actually increase-the overall costs of schizophrenia to society. The authors make recommendations aimed at reducing the cost by helping schizophrenic patients to be more productive through a system of community alternative-care facilities, increased rehabilitation services, aftercare, and research."} {"id": "PMID:168789", "title": "Psychomotor activity as a correlate of Depression and sleep in acutely disturbed psychiatric inpatients.", "content": "Combining a lightweight telemetric mobility sensing system with nightly EEG-sleep recordings, the authors obtained continuous monitoring of rest-activity cycles among psychiatric patients hospitalized for primary depression or acute schizophreniform thought disorder. The patients with primary depression had a significantly higher percentage of their total 24-hour motor activity distributed during the night. Furthermore, this increased nocturnal motor activity did not correlate significantly with concurrent EEG-sleep measures of wakefulness. Indeed, the best predictors of wakefulness were measures of daytime activity. This desynchronization of sleep and nighttime motor activity in primary depression may explain the need for combined pharmacotherapy in some severely depressed patients. The authors suggest that expressing activity as a percentage distribution function, rather than in terms of absolute amplitude, provides an objective diagnostic index of depression.", "contents": "Psychomotor activity as a correlate of Depression and sleep in acutely disturbed psychiatric inpatients. Combining a lightweight telemetric mobility sensing system with nightly EEG-sleep recordings, the authors obtained continuous monitoring of rest-activity cycles among psychiatric patients hospitalized for primary depression or acute schizophreniform thought disorder. The patients with primary depression had a significantly higher percentage of their total 24-hour motor activity distributed during the night. Furthermore, this increased nocturnal motor activity did not correlate significantly with concurrent EEG-sleep measures of wakefulness. Indeed, the best predictors of wakefulness were measures of daytime activity. This desynchronization of sleep and nighttime motor activity in primary depression may explain the need for combined pharmacotherapy in some severely depressed patients. The authors suggest that expressing activity as a percentage distribution function, rather than in terms of absolute amplitude, provides an objective diagnostic index of depression."} {"id": "PMID:168790", "title": "Sleep-related penile tumescence as a function of age.", "content": "The authors conducted a study of nocturnal penile tumescence (NPT) in 125 healthy males aged 3 to 79 by means of EEG recordings to provide normative data on how general the phenomenon is, its range of charateristics, and how it is related to man's sexual function. The results indicate that NPT occurs consistently in a healthy male population, that its expression is significantly affected by age, that it is related to stage of psychosexual development, and that it is worthy of further investigation. Clinical experience indicates that it is a useful, objective method of discriminating among various types of biogenic and psychogenic impotence.", "contents": "Sleep-related penile tumescence as a function of age. The authors conducted a study of nocturnal penile tumescence (NPT) in 125 healthy males aged 3 to 79 by means of EEG recordings to provide normative data on how general the phenomenon is, its range of charateristics, and how it is related to man's sexual function. The results indicate that NPT occurs consistently in a healthy male population, that its expression is significantly affected by age, that it is related to stage of psychosexual development, and that it is worthy of further investigation. Clinical experience indicates that it is a useful, objective method of discriminating among various types of biogenic and psychogenic impotence."} {"id": "PMID:168791", "title": "Tissue culture of the sera in human ulcerative colitis.", "content": "1. Control human sera had no effect on human amnion cell culture. 2. The sera from nineteen of twenty-one patients with ulcerative colitis had a marked cytopathic effect on cell cultures, suggesting an autoimmune effect. The sera of three of these showed an additional cytopathic effect on human amnion cell culture, suggesting a viral-like quality. 3. The sera from patients after total colectomy and protectomy for ulcerative colitis had no effect on cell cultures. 4. Rabbit antisera did not produce demonstrable antibodies or protect against the cytopathic effect in cell culture.", "contents": "Tissue culture of the sera in human ulcerative colitis. 1. Control human sera had no effect on human amnion cell culture. 2. The sera from nineteen of twenty-one patients with ulcerative colitis had a marked cytopathic effect on cell cultures, suggesting an autoimmune effect. The sera of three of these showed an additional cytopathic effect on human amnion cell culture, suggesting a viral-like quality. 3. The sera from patients after total colectomy and protectomy for ulcerative colitis had no effect on cell cultures. 4. Rabbit antisera did not produce demonstrable antibodies or protect against the cytopathic effect in cell culture."} {"id": "PMID:168792", "title": "The case against tylectomy for carcinoma of the breast. The factor of multicentricity.", "content": "Five hundred consecutive cases of breast carcinoma were studied to determine the incidence of multicentric lesions in the resected specimens. When residual tumor in juxtaposition to the primary tumor or biopsy cavity is excluded, 41.6 per cent of specimens exhibited multicentric foci of tumor; 31 per cent of such foci were in sectors or quadrants remote from the primary tumor. In more than half of these cases the lymph nodes were uninvolved and cure rate would have been maximal had these multicentric tumor foci been removed. These findings confirm previous similar studies and we consider tylectomy an inappropriate mode of therapy for breast cancer.", "contents": "The case against tylectomy for carcinoma of the breast. The factor of multicentricity. Five hundred consecutive cases of breast carcinoma were studied to determine the incidence of multicentric lesions in the resected specimens. When residual tumor in juxtaposition to the primary tumor or biopsy cavity is excluded, 41.6 per cent of specimens exhibited multicentric foci of tumor; 31 per cent of such foci were in sectors or quadrants remote from the primary tumor. In more than half of these cases the lymph nodes were uninvolved and cure rate would have been maximal had these multicentric tumor foci been removed. These findings confirm previous similar studies and we consider tylectomy an inappropriate mode of therapy for breast cancer."} {"id": "PMID:168794", "title": "Regeneration of single skeletal muscle fibers in vitro.", "content": "A culture system utilizing single skeletal muscle fibers from adult rats was developed to study the origin and behavior of mononucleated myoblasts during muscle regeneration. The single fibers are removed manually from the leg and thigh muscles at 300-400 gm rats and maintained in vitro embedded in a fibrin clot overlain with culture medium. Regenerative events were monitored by continuous observations of the cultured fibers. During the first few hours in vitro the fibers undergo degenerative changes including the formation of myofibrillar contraction clots and pyknosis of myonuclei. The endomysial tube (basement lamina) remains intact along the entire length of the fiber and forms transparent chambers bridging the contraction clots. Single fibers are free of endomysial cells and display no cellular outgrowth in cultures, except at the cut ends. In contrast, a rich outgrowth of endomysial connective tissue cells is found with bundles consisting of two or more fibers. Isolated mononucleated cells, presumed to be muscle satellite cells, are present within the endomysial tube of single fibers at the onset of the culture period. There is no evidence that myonuclei contribute to the formation of mononucleated cells. The satellite cells enlarge and begin to proliferate during the second day in vitro to form clones of presumptive myoblasts within the endomysial tube. The early clones have a cell doubling time of about 22 hours and exhibit mitotic synchrony. After 5-7 days in vitro the satellite cell progeny begin to fuse to form multinucleated myotubes within the endomysial tube of the original fiber. The myotubes display spontaneous contractile activity and may extend throughout the length of the endomysial tube.", "contents": "Regeneration of single skeletal muscle fibers in vitro. A culture system utilizing single skeletal muscle fibers from adult rats was developed to study the origin and behavior of mononucleated myoblasts during muscle regeneration. The single fibers are removed manually from the leg and thigh muscles at 300-400 gm rats and maintained in vitro embedded in a fibrin clot overlain with culture medium. Regenerative events were monitored by continuous observations of the cultured fibers. During the first few hours in vitro the fibers undergo degenerative changes including the formation of myofibrillar contraction clots and pyknosis of myonuclei. The endomysial tube (basement lamina) remains intact along the entire length of the fiber and forms transparent chambers bridging the contraction clots. Single fibers are free of endomysial cells and display no cellular outgrowth in cultures, except at the cut ends. In contrast, a rich outgrowth of endomysial connective tissue cells is found with bundles consisting of two or more fibers. Isolated mononucleated cells, presumed to be muscle satellite cells, are present within the endomysial tube of single fibers at the onset of the culture period. There is no evidence that myonuclei contribute to the formation of mononucleated cells. The satellite cells enlarge and begin to proliferate during the second day in vitro to form clones of presumptive myoblasts within the endomysial tube. The early clones have a cell doubling time of about 22 hours and exhibit mitotic synchrony. After 5-7 days in vitro the satellite cell progeny begin to fuse to form multinucleated myotubes within the endomysial tube of the original fiber. The myotubes display spontaneous contractile activity and may extend throughout the length of the endomysial tube."} {"id": "PMID:168795", "title": "Clinical and immunologic responses of calves with colostrally acquired maternal antibody against parainfluenza-3 virus to homologous viral infection.", "content": "Exposure of colostrum-deprived calves and calves with colostrally acquired maternal antibody to aerosols of parainfluenza-3 (PI-3) virus resulted in signs of infection, leukopenia, and shedding of virus from the nasal passages. However, infection was not as severe in calves with colostrally acquired maternal antibody as it was in colostrum-deprived calves which did not have antibody to PI-3 virus before they were exposed. All calves responded immunologically to PI-3 virus, as indicated by resistance to challenge exposure and subsequent development of virus-neutralizing antibody. However, levels of serum and nasal secretion (NS) antibody at 30 days after viral exposure were lower in calves with colostrally acquired maternal antibody than in colostrum-deprived calves, and a serum antibody response in the former was primarily indicated by an anamnestic response after challenge exposure. After calves were challenge exposed to PI-3 virus, serum and NS antibodies were increased in all calves, but antibody titers were generally lower for calves that had colostrally acquired maternal antibody before their exposure than for those that acquired antibody only after PI-3 viral infection.", "contents": "Clinical and immunologic responses of calves with colostrally acquired maternal antibody against parainfluenza-3 virus to homologous viral infection. Exposure of colostrum-deprived calves and calves with colostrally acquired maternal antibody to aerosols of parainfluenza-3 (PI-3) virus resulted in signs of infection, leukopenia, and shedding of virus from the nasal passages. However, infection was not as severe in calves with colostrally acquired maternal antibody as it was in colostrum-deprived calves which did not have antibody to PI-3 virus before they were exposed. All calves responded immunologically to PI-3 virus, as indicated by resistance to challenge exposure and subsequent development of virus-neutralizing antibody. However, levels of serum and nasal secretion (NS) antibody at 30 days after viral exposure were lower in calves with colostrally acquired maternal antibody than in colostrum-deprived calves, and a serum antibody response in the former was primarily indicated by an anamnestic response after challenge exposure. After calves were challenge exposed to PI-3 virus, serum and NS antibodies were increased in all calves, but antibody titers were generally lower for calves that had colostrally acquired maternal antibody before their exposure than for those that acquired antibody only after PI-3 viral infection."} {"id": "PMID:168796", "title": "Lesions and pathogenesis of disease in young calves experimentally induced by a bovine adenovirus type 5 isolated from a calf with weak calf syndrome.", "content": "Lesions induced in each of 9 young colostrum-deprived calves closely resembled lesions seen in naturally occurring \"weak calf syndrome\" of eastern Idaho and southwestern Montana. The disease was experimentally induced by intravenous injection of bovine adenovirus type 5 that had been isolated from a calf with weak calf syndrome...", "contents": "Lesions and pathogenesis of disease in young calves experimentally induced by a bovine adenovirus type 5 isolated from a calf with weak calf syndrome. Lesions induced in each of 9 young colostrum-deprived calves closely resembled lesions seen in naturally occurring \"weak calf syndrome\" of eastern Idaho and southwestern Montana. The disease was experimentally induced by intravenous injection of bovine adenovirus type 5 that had been isolated from a calf with weak calf syndrome..."} {"id": "PMID:168797", "title": "Canine adenovirus type 2-induced immunity to two canine adenoviruses in pups with maternal antibody.", "content": "Twenty-four Beagle pups with high levels of maternal antibody to canine adenovirus type 1 (CAV-1) and canine adenovirus type 2 (CAV-2) were oronasally inoculated with CAV-2 at 4 weeks of age. The CAV-2 was isolated from pharyngeal swabs on postinoculation days 2 through 6. In spite of the infection, maternal antibody continued to decrease for 4 to 8 postinoculation weeks, and then homologous CAV-2 neutralizing antibody and, to a lesser extent, CAV-1 neutralizing antibody began to increase. When these pups were challenge inoculated with CAV-1 and CAV-2 at a time when maternal antibody to CAV-1 would normally have disappeared, they were immune. In addition, 3 pups with maternal antibody to CAV-1 and CAV-2 were intramuscularly inoculated with CAV-2 at 3 weeks of age. Virus was not isolated from these pups, and maternal antibody decreased at a normal rate. These pups were not immune to challenge inoculation with CAV-1 and CAV-2.", "contents": "Canine adenovirus type 2-induced immunity to two canine adenoviruses in pups with maternal antibody. Twenty-four Beagle pups with high levels of maternal antibody to canine adenovirus type 1 (CAV-1) and canine adenovirus type 2 (CAV-2) were oronasally inoculated with CAV-2 at 4 weeks of age. The CAV-2 was isolated from pharyngeal swabs on postinoculation days 2 through 6. In spite of the infection, maternal antibody continued to decrease for 4 to 8 postinoculation weeks, and then homologous CAV-2 neutralizing antibody and, to a lesser extent, CAV-1 neutralizing antibody began to increase. When these pups were challenge inoculated with CAV-1 and CAV-2 at a time when maternal antibody to CAV-1 would normally have disappeared, they were immune. In addition, 3 pups with maternal antibody to CAV-1 and CAV-2 were intramuscularly inoculated with CAV-2 at 3 weeks of age. Virus was not isolated from these pups, and maternal antibody decreased at a normal rate. These pups were not immune to challenge inoculation with CAV-1 and CAV-2."} {"id": "PMID:168798", "title": "A herpesvirus-type agent associated with skin lesions of green sea turtles in aquaculture.", "content": "Nine successive groups of green sea turtles (Chelonia mydas) were observed in aquaculture during the posthatchling period. During the first 6 months of growth, each group underwent an epizootic of skin lesions, named gray-patch disease. Two types of skin lesions are associated with gray-patch disease: papules and, more characteristically, spreading gray patches which appear 7 to 8 weeks after hatching. In both types of lesions, intranuclear inclusions are found in keratinocytes in the malpighian layer of the epidermis. Electron microscopic examination of scrapings from lesions and biopsies revealed many viral particles, with features characteristic of the herpesvirus group. Transmission of gray-patch disease is possible with bacteria-free preparations of viral particles.", "contents": "A herpesvirus-type agent associated with skin lesions of green sea turtles in aquaculture. Nine successive groups of green sea turtles (Chelonia mydas) were observed in aquaculture during the posthatchling period. During the first 6 months of growth, each group underwent an epizootic of skin lesions, named gray-patch disease. Two types of skin lesions are associated with gray-patch disease: papules and, more characteristically, spreading gray patches which appear 7 to 8 weeks after hatching. In both types of lesions, intranuclear inclusions are found in keratinocytes in the malpighian layer of the epidermis. Electron microscopic examination of scrapings from lesions and biopsies revealed many viral particles, with features characteristic of the herpesvirus group. Transmission of gray-patch disease is possible with bacteria-free preparations of viral particles."} {"id": "PMID:168799", "title": "Influence of vaccination with avirulent herpesvirus on subsequent infection of chickens with virulent Marek's disease herpesvirus.", "content": "Vaccination of chickens with turkey herpesvirus (HVT) or attenuated Marek's disease herpesvirus (aMDHV) blocked infection with virulent MDHV (VMDHV) for approximately 5 weeks after contact exposure. However, there was no apparent blockage of infection when challenge virus was administered intraabdominally (IA). Evidence for infection with VMDHV was based on viral isolation by in vivo assay or by detecting precipitins to \"A\" antigen associated with virulent virus. The HVT stimulated production of neutralizing antibody against VMDHV in a high percentage of chickens, whereas the aMDHV was a comparatively poor inducer of such antibody. Despite this difference, both of the vaccinal viruses conferred protection against development of Marek's disease.", "contents": "Influence of vaccination with avirulent herpesvirus on subsequent infection of chickens with virulent Marek's disease herpesvirus. Vaccination of chickens with turkey herpesvirus (HVT) or attenuated Marek's disease herpesvirus (aMDHV) blocked infection with virulent MDHV (VMDHV) for approximately 5 weeks after contact exposure. However, there was no apparent blockage of infection when challenge virus was administered intraabdominally (IA). Evidence for infection with VMDHV was based on viral isolation by in vivo assay or by detecting precipitins to \"A\" antigen associated with virulent virus. The HVT stimulated production of neutralizing antibody against VMDHV in a high percentage of chickens, whereas the aMDHV was a comparatively poor inducer of such antibody. Despite this difference, both of the vaccinal viruses conferred protection against development of Marek's disease."} {"id": "PMID:168800", "title": "Fluorescent antibody test for rapid diagnosis of coronaviral enteritis of turkeys (bluecomb).", "content": "Intestinal tissues obtained from coronavirus-infected embryos and turkeys were examined by fluorescent antibody tissue section technique (FAT). Evidence of viral antigen was demonstrated in the cytoplasm of the intestinal epithelial cells covering the villi. Embryo intestines that were examined from 24 to 96 hours after inoculation were positive for immunofluorescence (IF), whereas bursa of Fabricius was negative. Poults hatched from infected embryos were examined at 2 days of age and were positive for IF. Coronaviral antigen was detected by FAT in the cytoplasm of intestinal epithelial cells of the jejunum, ileum, duodenum, and cecum in all turkeys that were examined from 24 hours to 28 days.", "contents": "Fluorescent antibody test for rapid diagnosis of coronaviral enteritis of turkeys (bluecomb). Intestinal tissues obtained from coronavirus-infected embryos and turkeys were examined by fluorescent antibody tissue section technique (FAT). Evidence of viral antigen was demonstrated in the cytoplasm of the intestinal epithelial cells covering the villi. Embryo intestines that were examined from 24 to 96 hours after inoculation were positive for immunofluorescence (IF), whereas bursa of Fabricius was negative. Poults hatched from infected embryos were examined at 2 days of age and were positive for IF. Coronaviral antigen was detected by FAT in the cytoplasm of intestinal epithelial cells of the jejunum, ileum, duodenum, and cecum in all turkeys that were examined from 24 hours to 28 days."} {"id": "PMID:168801", "title": "Cellular proliferation induced in the lung by cadmium aerosol.", "content": "Rats were exposed to a polydispersed aerosol of 0.1 per cent cadmium chloride in physiologic saline for a single period of 2 hours, and the evolution of damage was followed for a 10-day period. Control animals were unexposed rats and rats exposed to an aerosol of physiologic saline. Wet lung weight doubled by the fourth day in animals exposed to cadmium chloride, but not in the control groups. Apart from a transient increase in fluid content at 1 day, there was no evidence that the lung weight gain was due to inflammatory edema. Uptake of [3H]thymidine markedly increased during the first four days after exposure to cadmium chloride. Light autoradiography showed that [3H]thymidine labeling occurred almost exclusively in Type II alveolar cells at 1 day: later, the label appeared in interstitial cells and cells lying free within alveoli. These changes correlated well (r=0.70) with the increase in deoxyribonucleic acid on the fourth day after exposure. Uptake of [3H]thymidine and deoxyribonucleic acid content in rats exposed to cadmium chloride showed a significant difference from the control groups (P less than 0.001). These experiments demonstrate that exposure to cadmium chloride aerosol evokes a wave of cellular proliferation in rat lung. This finding is of interest, because heavy industrial exposure to cadmium in humans is known to be associated with severe physiologic impairment and anatomic damage.", "contents": "Cellular proliferation induced in the lung by cadmium aerosol. Rats were exposed to a polydispersed aerosol of 0.1 per cent cadmium chloride in physiologic saline for a single period of 2 hours, and the evolution of damage was followed for a 10-day period. Control animals were unexposed rats and rats exposed to an aerosol of physiologic saline. Wet lung weight doubled by the fourth day in animals exposed to cadmium chloride, but not in the control groups. Apart from a transient increase in fluid content at 1 day, there was no evidence that the lung weight gain was due to inflammatory edema. Uptake of [3H]thymidine markedly increased during the first four days after exposure to cadmium chloride. Light autoradiography showed that [3H]thymidine labeling occurred almost exclusively in Type II alveolar cells at 1 day: later, the label appeared in interstitial cells and cells lying free within alveoli. These changes correlated well (r=0.70) with the increase in deoxyribonucleic acid on the fourth day after exposure. Uptake of [3H]thymidine and deoxyribonucleic acid content in rats exposed to cadmium chloride showed a significant difference from the control groups (P less than 0.001). These experiments demonstrate that exposure to cadmium chloride aerosol evokes a wave of cellular proliferation in rat lung. This finding is of interest, because heavy industrial exposure to cadmium in humans is known to be associated with severe physiologic impairment and anatomic damage."} {"id": "PMID:168803", "title": "Colour television, an imitation of the human visual system.", "content": "Colour television is examined as an attempt to imitate the human visual system in image formation, spectral sensitivities, adaptation, contrast effects, signal processing, signal modulation, signal transmission, and interpretation. Many similarities are found, but where differences occur they are discussed in relation to the differences between visual and television technologies.", "contents": "Colour television, an imitation of the human visual system. Colour television is examined as an attempt to imitate the human visual system in image formation, spectral sensitivities, adaptation, contrast effects, signal processing, signal modulation, signal transmission, and interpretation. Many similarities are found, but where differences occur they are discussed in relation to the differences between visual and television technologies."} {"id": "PMID:168804", "title": "Ulcer simulating gastric carcinoma. II. Histopathology and survival.", "content": "Forty eight benign-ulcer-simulating gastric carcinomas treated at the Second Departmxamined histologically. Twenty two cases (46%) were classified as adenocarcinomas, 15 (31%) were mucocellular and 11 (23%) were anaplastic poorly differentiated forms. Invasion was limited in the histological specimens to the mucosa or submucosa in 20 cases (43%) which also fulfilled the criterias for early gastric carcinoma. The five year survival rate, by the actuarial method, was 63%, which is good if compared with that of all gastric carcinomas. The good prognosis can mainly be explained by the high percentage of early carcinoma for which the 5 year survival rate was 77%.", "contents": "Ulcer simulating gastric carcinoma. II. Histopathology and survival. Forty eight benign-ulcer-simulating gastric carcinomas treated at the Second Departmxamined histologically. Twenty two cases (46%) were classified as adenocarcinomas, 15 (31%) were mucocellular and 11 (23%) were anaplastic poorly differentiated forms. Invasion was limited in the histological specimens to the mucosa or submucosa in 20 cases (43%) which also fulfilled the criterias for early gastric carcinoma. The five year survival rate, by the actuarial method, was 63%, which is good if compared with that of all gastric carcinomas. The good prognosis can mainly be explained by the high percentage of early carcinoma for which the 5 year survival rate was 77%."} {"id": "PMID:168805", "title": "A case of malignant arrhenoblastoma.", "content": "The patient was a 72-year-old married woman from whom a recurrent arrhenoblastoma had been removed three time in the course of six years. She was clearly virilized and her voice had become deep. Endocrine studies before removal of the recurrences showed pronounced elevation of the serum testosterone values. The 17-KS values did not as clearly parallel growth of the tumour. Histochemical examination showed moderate 3beta-steroid dehydrogenase activity in limited areas. The histological features were those of so-called intermediate type of arrhenoblastoma with a very scanty tubular component. Histologically the tumour was malignant, but with a relatively low degree of malignancy. Regardless of the treatment there was twice a recurrence of the tumour. The increase of the serum testosterone values during the follow-up period reflected recurrence on of the tumour.", "contents": "A case of malignant arrhenoblastoma. The patient was a 72-year-old married woman from whom a recurrent arrhenoblastoma had been removed three time in the course of six years. She was clearly virilized and her voice had become deep. Endocrine studies before removal of the recurrences showed pronounced elevation of the serum testosterone values. The 17-KS values did not as clearly parallel growth of the tumour. Histochemical examination showed moderate 3beta-steroid dehydrogenase activity in limited areas. The histological features were those of so-called intermediate type of arrhenoblastoma with a very scanty tubular component. Histologically the tumour was malignant, but with a relatively low degree of malignancy. Regardless of the treatment there was twice a recurrence of the tumour. The increase of the serum testosterone values during the follow-up period reflected recurrence on of the tumour."} {"id": "PMID:168802", "title": "Idiopathic facial paralysis, pregnancy, and the menstrual cycle.", "content": "The records of 42 women with Bell's palsy during pregnancy, and of 91 nonpregnant women, whose dats of onset of Bell's palsy and of the preceding menstrual cycle were precisely known, were studied for factors that might show relation between pregnancy or the menstrual cycle and Bell's palsy. Of the 42 cases in pregnancy, 31 occurred in the third trimester, five in the first two weeks postpartum, and six in the first two trimesters combined. Our calculated frequency of Bell's palsy in pregnant women is 45.1/100,000 births; for nonpregnant women of the same age group the calculated incidence is 17.4/100,000 per year. No causative relation was found between toxemia, hypertension or primigravidity, and Bell's palsy. Over 60% of the cases in nonpregnant women occurred in the first 14 days of the menstrual cycle with peaks on the first and seventh days and near ovulation. No clear evidence for an etiologic relationship was seen with edema or hormonal changes in either pregnancy or the menstrual cycle. A number of factors in pregnancy and the menstrual cycle suggested an etiologic role for herpes simplex virus reactivation in Bell's palsy. There was no evidence that prednisone treatment is contraindicated during pregnancy.", "contents": "Idiopathic facial paralysis, pregnancy, and the menstrual cycle. The records of 42 women with Bell's palsy during pregnancy, and of 91 nonpregnant women, whose dats of onset of Bell's palsy and of the preceding menstrual cycle were precisely known, were studied for factors that might show relation between pregnancy or the menstrual cycle and Bell's palsy. Of the 42 cases in pregnancy, 31 occurred in the third trimester, five in the first two weeks postpartum, and six in the first two trimesters combined. Our calculated frequency of Bell's palsy in pregnant women is 45.1/100,000 births; for nonpregnant women of the same age group the calculated incidence is 17.4/100,000 per year. No causative relation was found between toxemia, hypertension or primigravidity, and Bell's palsy. Over 60% of the cases in nonpregnant women occurred in the first 14 days of the menstrual cycle with peaks on the first and seventh days and near ovulation. No clear evidence for an etiologic relationship was seen with edema or hormonal changes in either pregnancy or the menstrual cycle. A number of factors in pregnancy and the menstrual cycle suggested an etiologic role for herpes simplex virus reactivation in Bell's palsy. There was no evidence that prednisone treatment is contraindicated during pregnancy."} {"id": "PMID:168806", "title": "Inhibition of Coccidioides immitis in vitro and enhancement of antiococcidiodial effects of amphotericin B by polymyxin B.", "content": "Growth of the spherule phase of Coccidioides immitis in liquid glucose-mineral salts medium was suppressed for 13 days by 5 to 10 mug of polymyxin B per ml. Inhibition of growth was also noted when filter paper disks containing polymyxin B were placed on the surface of arthrospore-seeded defined medium solidified with refined agar. The antibiotic evidently damaged the cytoplasmic membrane inasmuch as spherules suspended in distilled water containing 10 mug of polymyxin B per ml rapidly lost nucleotides. Leakage of nucleotides was prevented by 0.1 M Ca(2+). The anticoccidioidal activity of amphotericin B (0.02 to 0.08 mug/ml) was enhanced by 2.5 mug of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 mug/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its gamma-amino groups are masked by methanesulfonate radicals.", "contents": "Inhibition of Coccidioides immitis in vitro and enhancement of antiococcidiodial effects of amphotericin B by polymyxin B. Growth of the spherule phase of Coccidioides immitis in liquid glucose-mineral salts medium was suppressed for 13 days by 5 to 10 mug of polymyxin B per ml. Inhibition of growth was also noted when filter paper disks containing polymyxin B were placed on the surface of arthrospore-seeded defined medium solidified with refined agar. The antibiotic evidently damaged the cytoplasmic membrane inasmuch as spherules suspended in distilled water containing 10 mug of polymyxin B per ml rapidly lost nucleotides. Leakage of nucleotides was prevented by 0.1 M Ca(2+). The anticoccidioidal activity of amphotericin B (0.02 to 0.08 mug/ml) was enhanced by 2.5 mug of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 mug/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its gamma-amino groups are masked by methanesulfonate radicals."} {"id": "PMID:168807", "title": "In vitro additive effect of polymxin B and rifampin against Serratia marcesen.", "content": "The combination of polymyxin B and rifampin resulted in an additive effect against all 12 clinical isolates of Serratia marcescens examined, including multiple-drug-resistant isolates.", "contents": "In vitro additive effect of polymxin B and rifampin against Serratia marcesen. The combination of polymyxin B and rifampin resulted in an additive effect against all 12 clinical isolates of Serratia marcescens examined, including multiple-drug-resistant isolates."} {"id": "PMID:168808", "title": "Regulation of aspartokinase and homoserine dehydrogenase in acetic acid bacteria.", "content": "The regulation of aspartokinase and homoserine dehydrogenase has been studied in three Acetobacter and two Gluconobacter species. Both enzymes were regulated by feedback inhibition. Aspartokinase was inhibited by L-threonine and concertedly inhibited by L-threonine plus L-lysine. The homoserine dehydrogenase was NADP-specific and was inhibited by L-threonine. Separation of the two enzymes by ammonium sulphate fractionation was possible in Acetobacter peroxydans, A. rancens and Gluconobacter melanogenus but not in A. liquefaciens or G. oxydans.", "contents": "Regulation of aspartokinase and homoserine dehydrogenase in acetic acid bacteria. The regulation of aspartokinase and homoserine dehydrogenase has been studied in three Acetobacter and two Gluconobacter species. Both enzymes were regulated by feedback inhibition. Aspartokinase was inhibited by L-threonine and concertedly inhibited by L-threonine plus L-lysine. The homoserine dehydrogenase was NADP-specific and was inhibited by L-threonine. Separation of the two enzymes by ammonium sulphate fractionation was possible in Acetobacter peroxydans, A. rancens and Gluconobacter melanogenus but not in A. liquefaciens or G. oxydans."} {"id": "PMID:168809", "title": "Demonstration of virus in groundwater after effluent discharge onto soil.", "content": "The survival of virus present in secondary effluents discharged into a cypress dome was studied. Isolations were made from concentrates of water drawn from 10-foot (304.80 cm) deep wells. Data presented show vertical and lateral virus movement as well as survival within the dome for 28 days during a period of heavy rains when no effluent was being applied. Due to the inefficiency of virus concentration procedures, it is proposed that much of the virus present was probably not demonstrated. A rapid, relatively inexpensive concentration technique for sewage influents and effluents is discussed.", "contents": "Demonstration of virus in groundwater after effluent discharge onto soil. The survival of virus present in secondary effluents discharged into a cypress dome was studied. Isolations were made from concentrates of water drawn from 10-foot (304.80 cm) deep wells. Data presented show vertical and lateral virus movement as well as survival within the dome for 28 days during a period of heavy rains when no effluent was being applied. Due to the inefficiency of virus concentration procedures, it is proposed that much of the virus present was probably not demonstrated. A rapid, relatively inexpensive concentration technique for sewage influents and effluents is discussed."} {"id": "PMID:168810", "title": "Radiation resistance of spores of some Clostridium perfringens strains.", "content": "Clostridium perfringens spores (eight strains) were irradiated in a model system with 60Co gamma rays at -30 C. The quantal response data obtained were analyzed with extreme value statistics. It was found (at the 95% confidence level) that all eight strains followed the same rate of death and that this rate was probably (at the 95% level) not exponential. The statistics did not exclude, however, a normal, lognormal, Weibull, or related rate of spore kill. A more definitive study would be required to distinguish between the latter distributions.", "contents": "Radiation resistance of spores of some Clostridium perfringens strains. Clostridium perfringens spores (eight strains) were irradiated in a model system with 60Co gamma rays at -30 C. The quantal response data obtained were analyzed with extreme value statistics. It was found (at the 95% confidence level) that all eight strains followed the same rate of death and that this rate was probably (at the 95% level) not exponential. The statistics did not exclude, however, a normal, lognormal, Weibull, or related rate of spore kill. A more definitive study would be required to distinguish between the latter distributions."} {"id": "PMID:168817", "title": "Familial chondrocalcinosis in the Chiloe Islands, Chile.", "content": "Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group.", "contents": "Familial chondrocalcinosis in the Chiloe Islands, Chile. Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group."} {"id": "PMID:168818", "title": "Fine structural changes at Entamoeba histolytica rabbit kidney cell (RK 13) interface.", "content": "When bacteria-free trophozoites of Entamoeba histolytica were added to a monolayer of rabbit kidney cells, cellular injury occurred at the sites of contact. Changes appeared within the cell cytoplasm before there was any generalized cell membrane damage. At some points of contact there was apparent fusion of amoebic and cell cytoplasm. Electron-dense bodies, here interpreted as liposomes, were present in the amoebic cytoplasm and beneath the surface membrane. No surface lysosomes were seen. Various modes of cell damage and enzyme transfer from amoeba to cell are suggested, together with the possibility that cytopathic amoebae are infected with virus particles.", "contents": "Fine structural changes at Entamoeba histolytica rabbit kidney cell (RK 13) interface. When bacteria-free trophozoites of Entamoeba histolytica were added to a monolayer of rabbit kidney cells, cellular injury occurred at the sites of contact. Changes appeared within the cell cytoplasm before there was any generalized cell membrane damage. At some points of contact there was apparent fusion of amoebic and cell cytoplasm. Electron-dense bodies, here interpreted as liposomes, were present in the amoebic cytoplasm and beneath the surface membrane. No surface lysosomes were seen. Various modes of cell damage and enzyme transfer from amoeba to cell are suggested, together with the possibility that cytopathic amoebae are infected with virus particles."} {"id": "PMID:168819", "title": "Experimental transmission of Japanese encephalitis virus by Culex tritaeniorhynchus and C. fuscocephalus.", "content": "Experimental transmission of Japanese encephalitis virus from swine to baby chicks was accomplished using Culex tritaeniorhynchus and Culex fuscocephalus, two of three mosquito species in Taiwan from which the virus has been recovered in nature. Whereas neither species had become infective by the twelfth day, one of ten C. fuscocephalus and 11 of 51 C. tritaeniorhynchus were infective by the seventeenth day of extrinsic incubation as verified by viraemia in chicks fed upon by potentially infective mosquitoes. The highest transmission rate obtained was 81% for C. tritaeniorhynchus on the twenty-first day of extrinsic incubation.", "contents": "Experimental transmission of Japanese encephalitis virus by Culex tritaeniorhynchus and C. fuscocephalus. Experimental transmission of Japanese encephalitis virus from swine to baby chicks was accomplished using Culex tritaeniorhynchus and Culex fuscocephalus, two of three mosquito species in Taiwan from which the virus has been recovered in nature. Whereas neither species had become infective by the twelfth day, one of ten C. fuscocephalus and 11 of 51 C. tritaeniorhynchus were infective by the seventeenth day of extrinsic incubation as verified by viraemia in chicks fed upon by potentially infective mosquitoes. The highest transmission rate obtained was 81% for C. tritaeniorhynchus on the twenty-first day of extrinsic incubation."} {"id": "PMID:168821", "title": "Inhibition of lipolysis and cyclic AMP accumulation in white fat cells by tetracycline.", "content": "The effects of tetracycline on the metabolism of isolated rat white fat cells were examined. Tetracycline at a concentration of 0.05 mg/ml inhibited lipolysis due to 0.075 or 0.15 muM norepinephrine, but not that due to adenosine deaminase, theophylline, dibutyryl cyclic AMP or 1.5 muM norepinephrine. Higher concentrations of tetracycline (1 mg/ml) inhibited lipolysis due to all added agents except dibutyryl cyclic AMP. The accumulation of cyclic AMP after 5 minutes incubation with 0.15 muM norepinephrine plus adenosine deaminase was inhibited by 0.05 mg/ml of tetracycline. The large rise in cyclic AMP accumulation at 5 minutes due to 1.5 muM norepinephrine in the presence of 100 muM theophylline was only slightly inhibited by 0.05 or 0.1 mg/ml of tetracycline. Tetracycline at 1 mg/ml did markedly inhibit cyclic AMP accumulation due to all added agents. The stimulation of adenylate cyclase activity of fat cell ghosts by norepinephrine or fluoride was inhibited by 0.05 mg/ml or greater concentration of tetracycline. Insulin-stimulated glucose oxidation by fat cells was inhibited by 1 mg/ml of tetracycline. These results suggest that the anti-lipolytic action of tetracycline on rat fat cells is secondary to inhibition of cyclic AMP accumulation.", "contents": "Inhibition of lipolysis and cyclic AMP accumulation in white fat cells by tetracycline. The effects of tetracycline on the metabolism of isolated rat white fat cells were examined. Tetracycline at a concentration of 0.05 mg/ml inhibited lipolysis due to 0.075 or 0.15 muM norepinephrine, but not that due to adenosine deaminase, theophylline, dibutyryl cyclic AMP or 1.5 muM norepinephrine. Higher concentrations of tetracycline (1 mg/ml) inhibited lipolysis due to all added agents except dibutyryl cyclic AMP. The accumulation of cyclic AMP after 5 minutes incubation with 0.15 muM norepinephrine plus adenosine deaminase was inhibited by 0.05 mg/ml of tetracycline. The large rise in cyclic AMP accumulation at 5 minutes due to 1.5 muM norepinephrine in the presence of 100 muM theophylline was only slightly inhibited by 0.05 or 0.1 mg/ml of tetracycline. Tetracycline at 1 mg/ml did markedly inhibit cyclic AMP accumulation due to all added agents. The stimulation of adenylate cyclase activity of fat cell ghosts by norepinephrine or fluoride was inhibited by 0.05 mg/ml or greater concentration of tetracycline. Insulin-stimulated glucose oxidation by fat cells was inhibited by 1 mg/ml of tetracycline. These results suggest that the anti-lipolytic action of tetracycline on rat fat cells is secondary to inhibition of cyclic AMP accumulation."} {"id": "PMID:168823", "title": "Familial hyperalphalipoproteinemia.", "content": "A 26-member kindred had the newly recognized heritable hyperlipoproteinemia, familial hyperalphalipoproteinemia. In affected family members, hyperalphalipoproteinemia was not secondary to any diseases, drugs, or industrial exposures known to elevate alpha-lipoprotein (high-density) cholesterol (C-HDL) levels. Hyperalphalipoproteinemia was transmitted vertically through three generations. There were five matings of hyperalphalipoproteinemic to normal individuals, with 25 offspring. The ratio of offspring with elevated C-HDL levels to those with normal C-HDL levels was 12:13 (0.923), a ratio not significantly different from 1 (x2 equals 0.04), the ratio predicted for an autosomal dominant trait. In affected kindred members, levels of total plasma cholesterol were slightly elevated, those of low density lipoprotein cholesterol were normal to low, those of triglyceride were normal, and those of C-HDL were consistently elevated. Affected subjects were healthy, without xanthomata, and had no unique physical or neurological features.", "contents": "Familial hyperalphalipoproteinemia. A 26-member kindred had the newly recognized heritable hyperlipoproteinemia, familial hyperalphalipoproteinemia. In affected family members, hyperalphalipoproteinemia was not secondary to any diseases, drugs, or industrial exposures known to elevate alpha-lipoprotein (high-density) cholesterol (C-HDL) levels. Hyperalphalipoproteinemia was transmitted vertically through three generations. There were five matings of hyperalphalipoproteinemic to normal individuals, with 25 offspring. The ratio of offspring with elevated C-HDL levels to those with normal C-HDL levels was 12:13 (0.923), a ratio not significantly different from 1 (x2 equals 0.04), the ratio predicted for an autosomal dominant trait. In affected kindred members, levels of total plasma cholesterol were slightly elevated, those of low density lipoprotein cholesterol were normal to low, those of triglyceride were normal, and those of C-HDL were consistently elevated. Affected subjects were healthy, without xanthomata, and had no unique physical or neurological features."} {"id": "PMID:168820", "title": "Plasmalipoproteins and atherosclerosis.", "content": "The author describes and classifies the different types of lipo-proteins and their connection with the various types of hyperlipoproteinemias and he discusses their possible role in producing atherosclerosis.", "contents": "Plasmalipoproteins and atherosclerosis. The author describes and classifies the different types of lipo-proteins and their connection with the various types of hyperlipoproteinemias and he discusses their possible role in producing atherosclerosis."} {"id": "PMID:168824", "title": "Partial deficiency of hepatic glucose-6-phosphatase in an adult patient.", "content": "Patients with hepatic glucose-6-phosphatase deficiency usually have a striking clinical syndrome during childhood and are readily diagnosed by the pediatrician. An adult patient had childhood manifestations of glucose-6-phosphatase deficiency that were mild and unrecognized; symptoms of tophaceous gout, urate nephropathy and characteristic blood chemical studies suggested the diagnosis at age 39. Subsequent epinephrine and galactose tolerance tests were characteristic of hepatic glucose-6-phosphatase deficiency and direct assay of hepatic glucose-6-phosphatase confirmed a partial deficiency of the enzyme. The case emphasized that patients with this deficiency may escape diagnosis during childhood and that internists should consider the diagnosis in adolescents or young adults with acute gouty arthritis or tophaceous gout.", "contents": "Partial deficiency of hepatic glucose-6-phosphatase in an adult patient. Patients with hepatic glucose-6-phosphatase deficiency usually have a striking clinical syndrome during childhood and are readily diagnosed by the pediatrician. An adult patient had childhood manifestations of glucose-6-phosphatase deficiency that were mild and unrecognized; symptoms of tophaceous gout, urate nephropathy and characteristic blood chemical studies suggested the diagnosis at age 39. Subsequent epinephrine and galactose tolerance tests were characteristic of hepatic glucose-6-phosphatase deficiency and direct assay of hepatic glucose-6-phosphatase confirmed a partial deficiency of the enzyme. The case emphasized that patients with this deficiency may escape diagnosis during childhood and that internists should consider the diagnosis in adolescents or young adults with acute gouty arthritis or tophaceous gout."} {"id": "PMID:168825", "title": "Noradrenaline-secreting glomus jugulare tumor with cyclic change of blood pressure.", "content": "A glomus jugulare tumor secreted a large quantity of noradrenaline (NA) and produced symptoms of tinnitus, palpitation, sweating, and labile hypertension. The NA content of the tumor was 0.75 mg/gm of tissue. Electron microscopical study of the tumor demonstrated many membrane-limited osmiophilic granules. This indicates the capacity of the tumor not only to synthesize but also to store NA in the tumor. Continuous blood pressure recording showed a cyclic change of blood pressure with a cycle length of 10 to 17 minutes that terminated after intravenous doses of phentolamine (0.1 mg/kg) or diazoxide (4.5 mg/kg) and surgical removal of the tumor.", "contents": "Noradrenaline-secreting glomus jugulare tumor with cyclic change of blood pressure. A glomus jugulare tumor secreted a large quantity of noradrenaline (NA) and produced symptoms of tinnitus, palpitation, sweating, and labile hypertension. The NA content of the tumor was 0.75 mg/gm of tissue. Electron microscopical study of the tumor demonstrated many membrane-limited osmiophilic granules. This indicates the capacity of the tumor not only to synthesize but also to store NA in the tumor. Continuous blood pressure recording showed a cyclic change of blood pressure with a cycle length of 10 to 17 minutes that terminated after intravenous doses of phentolamine (0.1 mg/kg) or diazoxide (4.5 mg/kg) and surgical removal of the tumor."} {"id": "PMID:168826", "title": "The respiratory electron transport system of heterotrophically-grown Rhodopseudomonas palustris.", "content": "The enzymatic activities and the cytochrome components of the respiratory chain were investigated with membrane fractions from chemoheterotrophically growth Rhodopseudomonas palustris. Whereas the level of electron transfer carriers was not distinctly affected by a change of the culture conditions, the potential activities of the enzymes were clearly increased when the cells were grown aerobically. Reduced-minus oxidized difference spectra of the membrane fractions prepared from dark aerobically grown cells revealed the presence of three beta-types cytochromes b561, b560 and b558, and at least two c-type cytochromes c556 and c2 as electron carriers in the electron transfer chain. Cytochrome of a-type could not be detected in these membranes. Reduced plus CO minus reduced difference spectra of the membrane fractions were indicative of cytochrome o, which may be equivalent to cytochrome b560, appearing in substrate-reduced minus oxidized difference spectra. Cytochrome o was found to be the functional terminal oxidase. CO difference spectra of the high speed supernatant fraction indicated the presence of cytochrome c'. Succinate and NADH reduced the same types of cytochromes. However, a considerable amount of cytochrome b561 with associated beta and gamma bands at 531 and 429 nm, respectively, was reducible by succinate, but not by NADH. A substantial fraction of the membrane-bound b-type cytochrome was non-substrate reducible and was found in dithionite-reduced minus substrate-reduced spectra. Cytochrome c2 may be localized in a branch of the electron transport system, with the branch-point at the level of ubiquinone. The separate pathways rejoined at a common terminal oxidase. Two terminal oxidases with different KCN sensitivity were present in the respiratory chain, one of which was sensitive to low concentrations of KCN and was connected with the cytochrome chain. The other terminal oxidase which was inhibited only by high concentrations of cyanide was located in a branched pathway, through which the electrons could flow from ubiquinone to oxygen bypassing the cytochrome chain.", "contents": "The respiratory electron transport system of heterotrophically-grown Rhodopseudomonas palustris. The enzymatic activities and the cytochrome components of the respiratory chain were investigated with membrane fractions from chemoheterotrophically growth Rhodopseudomonas palustris. Whereas the level of electron transfer carriers was not distinctly affected by a change of the culture conditions, the potential activities of the enzymes were clearly increased when the cells were grown aerobically. Reduced-minus oxidized difference spectra of the membrane fractions prepared from dark aerobically grown cells revealed the presence of three beta-types cytochromes b561, b560 and b558, and at least two c-type cytochromes c556 and c2 as electron carriers in the electron transfer chain. Cytochrome of a-type could not be detected in these membranes. Reduced plus CO minus reduced difference spectra of the membrane fractions were indicative of cytochrome o, which may be equivalent to cytochrome b560, appearing in substrate-reduced minus oxidized difference spectra. Cytochrome o was found to be the functional terminal oxidase. CO difference spectra of the high speed supernatant fraction indicated the presence of cytochrome c'. Succinate and NADH reduced the same types of cytochromes. However, a considerable amount of cytochrome b561 with associated beta and gamma bands at 531 and 429 nm, respectively, was reducible by succinate, but not by NADH. A substantial fraction of the membrane-bound b-type cytochrome was non-substrate reducible and was found in dithionite-reduced minus substrate-reduced spectra. Cytochrome c2 may be localized in a branch of the electron transport system, with the branch-point at the level of ubiquinone. The separate pathways rejoined at a common terminal oxidase. Two terminal oxidases with different KCN sensitivity were present in the respiratory chain, one of which was sensitive to low concentrations of KCN and was connected with the cytochrome chain. The other terminal oxidase which was inhibited only by high concentrations of cyanide was located in a branched pathway, through which the electrons could flow from ubiquinone to oxygen bypassing the cytochrome chain."} {"id": "PMID:168827", "title": "The electron transport system of the anaerobic Propionibacterium shermanii: cytochrome and inhibitor studies.", "content": "1. Electron transport particles obtained from cell-free extracts of Propionibacterium shermanii by centrifugation at 105000 times g for 3 hrs oxidized NADH, D,L-lactate, L-glycerol-3-phosphate and succinate with oxygen and, except for succinate, with fumarate, too. 2. Spectral investigation of the electron transport particles revealed the presence of cytochromes b, d and o, and traces of cytochrome alpha1 and a c-type cytochrome. Cytochrome b was reduced by succinate to about 50%, and by NADH, lactate or glycerol-3-phosphate to 80--90%. 3. The inhibitory effects of amytal and rotenone on NADH oxidation, but not on the oxidation of the other substrates, indicated the presence of the NADH dehydrogenase complex, or \"site I region\", in the electron transport system of P. shermanii. 4. NQNO inhibited substrate oxidations by oxygen and fumarate, as well as equilibration of the flavoproteins of the substrate dehydrogenases by way of menaquinone. The inhibition occurred at low concentrations of the inhibitor and reached 80--100%, depending on the substrate tested. The site of inhibition of the respiratory activity was located between menaquinone and cytochrome b. In addition, inhibition of flavoprotein equilibration suggested that NQNO acted upon the electron transfer directed from menaquinol towards the acceptor to be reduced, either cytochrome b or the flavoproteins, which would include fumarate reductase. 5. In NQNO-inhibited particles, cytochrome b was not oxidized by oxygen-free fumarate, but readily oxidized by oxygen. It was concluded from this and the above evidence that the branching-point of the electron transport chain towards fumarate reductase was located at the menaquinone in P. shermanii. It was further concluded that all cytochromes were situated in the oxygen-linked branch of the chain, which formed a dead end of the system under anaerobic conditions. 6. Antimycin A inhibited only oxygen-linked reactions of the particles to about 50% at high concentrations of the inhibitor. Inhibitors of terminal oxidases were inactive, except for carbon monoxide.", "contents": "The electron transport system of the anaerobic Propionibacterium shermanii: cytochrome and inhibitor studies. 1. Electron transport particles obtained from cell-free extracts of Propionibacterium shermanii by centrifugation at 105000 times g for 3 hrs oxidized NADH, D,L-lactate, L-glycerol-3-phosphate and succinate with oxygen and, except for succinate, with fumarate, too. 2. Spectral investigation of the electron transport particles revealed the presence of cytochromes b, d and o, and traces of cytochrome alpha1 and a c-type cytochrome. Cytochrome b was reduced by succinate to about 50%, and by NADH, lactate or glycerol-3-phosphate to 80--90%. 3. The inhibitory effects of amytal and rotenone on NADH oxidation, but not on the oxidation of the other substrates, indicated the presence of the NADH dehydrogenase complex, or \"site I region\", in the electron transport system of P. shermanii. 4. NQNO inhibited substrate oxidations by oxygen and fumarate, as well as equilibration of the flavoproteins of the substrate dehydrogenases by way of menaquinone. The inhibition occurred at low concentrations of the inhibitor and reached 80--100%, depending on the substrate tested. The site of inhibition of the respiratory activity was located between menaquinone and cytochrome b. In addition, inhibition of flavoprotein equilibration suggested that NQNO acted upon the electron transfer directed from menaquinol towards the acceptor to be reduced, either cytochrome b or the flavoproteins, which would include fumarate reductase. 5. In NQNO-inhibited particles, cytochrome b was not oxidized by oxygen-free fumarate, but readily oxidized by oxygen. It was concluded from this and the above evidence that the branching-point of the electron transport chain towards fumarate reductase was located at the menaquinone in P. shermanii. It was further concluded that all cytochromes were situated in the oxygen-linked branch of the chain, which formed a dead end of the system under anaerobic conditions. 6. Antimycin A inhibited only oxygen-linked reactions of the particles to about 50% at high concentrations of the inhibitor. Inhibitors of terminal oxidases were inactive, except for carbon monoxide."} {"id": "PMID:168828", "title": "Physiological role for the membrane bound ascorbate-TMPD oxidase in pseudomonas putida.", "content": "The activity of the membrane-bound ascorbate-TMPD oxidase in Pseudomonas putida varies with growth conditions and age of the culture. A comparison of the effects of cyanide and azide on the oxidation of various substrates suggests that ascorbate-TMPD oxidase is not the terminal oxidase for NADH or succinate oxidation. However, it does have a role in the oxidation of nicotinate, and may act as an additional terminal oxidase under certain other growth conditions.", "contents": "Physiological role for the membrane bound ascorbate-TMPD oxidase in pseudomonas putida. The activity of the membrane-bound ascorbate-TMPD oxidase in Pseudomonas putida varies with growth conditions and age of the culture. A comparison of the effects of cyanide and azide on the oxidation of various substrates suggests that ascorbate-TMPD oxidase is not the terminal oxidase for NADH or succinate oxidation. However, it does have a role in the oxidation of nicotinate, and may act as an additional terminal oxidase under certain other growth conditions."} {"id": "PMID:168829", "title": "Kinetics and morphology of glucose-limited cultures of moulds grown in a chemostat and on solid media.", "content": "The affinity (KS value) of Geotrichum candidum for glucose determined from chemostate cultures was ca. 1 mg/1. KS values for glucose was also estimated from the radial growth rates of colonies of G. candidum and Neurospora crassa grown on media solidified with agar or silica gel. An assessment is made of the use of colony radial growth rate to determine substrate affinities. The length of apical and intercalary hyphal comparte ments, internode length and the diameter of leading hyphaat the margin of colonies grown on solid media were all reduced at low glucose concentrations.", "contents": "Kinetics and morphology of glucose-limited cultures of moulds grown in a chemostat and on solid media. The affinity (KS value) of Geotrichum candidum for glucose determined from chemostate cultures was ca. 1 mg/1. KS values for glucose was also estimated from the radial growth rates of colonies of G. candidum and Neurospora crassa grown on media solidified with agar or silica gel. An assessment is made of the use of colony radial growth rate to determine substrate affinities. The length of apical and intercalary hyphal comparte ments, internode length and the diameter of leading hyphaat the margin of colonies grown on solid media were all reduced at low glucose concentrations."} {"id": "PMID:168830", "title": "Lactate dehydrogenases in cyanobacteria.", "content": "NAD-linked lactate dehydrogenases specific for the D- and L-lactate have been demonstrated in a number of strains of unicellular cyanobacteria. The D-lactate dehydrogenase of one strain (Synechococcus 6716) was partially purified and its properties were studied. The enzyme has a molecular weight of ca. 115000-120000, is highly specific, autooxidizable, and susceptible to inhibition by iodoacetamide, oxamate and ATP. The possible physiological functions of the enzyme in the metabolism of the organism were investigated. D-lactate carbon was incorporated in cell material during photosynthetic growth with CO2, but lactate was not used as sole source for carbon for photosynthetic or chemosynthetic development. D-lactate and pyruvate were oxidized aerobically in the dark by resting cell suspensions with the assimilation mainly of the C2 and the C3 carbon atoms. In the oxidation of lactate, acetate was excreted into the medium. No fermentation of glucose was found, but a small amount of D-lactate was detected as a product of endogenous dark metabolism of the cell. All enzymes required for the production of lactate from glucose and from glycogen were found in exponentially growing cells, but the activity of some key enzymes was low or undetectable in old cultures.", "contents": "Lactate dehydrogenases in cyanobacteria. NAD-linked lactate dehydrogenases specific for the D- and L-lactate have been demonstrated in a number of strains of unicellular cyanobacteria. The D-lactate dehydrogenase of one strain (Synechococcus 6716) was partially purified and its properties were studied. The enzyme has a molecular weight of ca. 115000-120000, is highly specific, autooxidizable, and susceptible to inhibition by iodoacetamide, oxamate and ATP. The possible physiological functions of the enzyme in the metabolism of the organism were investigated. D-lactate carbon was incorporated in cell material during photosynthetic growth with CO2, but lactate was not used as sole source for carbon for photosynthetic or chemosynthetic development. D-lactate and pyruvate were oxidized aerobically in the dark by resting cell suspensions with the assimilation mainly of the C2 and the C3 carbon atoms. In the oxidation of lactate, acetate was excreted into the medium. No fermentation of glucose was found, but a small amount of D-lactate was detected as a product of endogenous dark metabolism of the cell. All enzymes required for the production of lactate from glucose and from glycogen were found in exponentially growing cells, but the activity of some key enzymes was low or undetectable in old cultures."} {"id": "PMID:168831", "title": "Enzymes of glycollate formation and oxidation in two members of the rhodospirillacae (purple non-sulphur bacteria).", "content": "1. Phototrophic cultures of Rhodomicrobium vanielii do not excrete glycollate when gassed anaerobically with nitrogen plus carbon dioxide, although the addition of alpha-hydroxy-2-pyridine methanesulphonate (HPMS) results in the excretion of a trace amount of glycollate. The inclucion of low amounts of oxygen in this gas mixture results in marked glycollate excretion, higher rates occurring in the presence of HPMS. 2. Cell extracts of Rhodomicrobium vannielii, and also of Rhodospirillum rubrum, which excretes glycollate only under aerobic conditions in the light, catalyze the formation of glycollate from phosphoglycollate and also the oxidation of glycollate to glyoxylate.", "contents": "Enzymes of glycollate formation and oxidation in two members of the rhodospirillacae (purple non-sulphur bacteria). 1. Phototrophic cultures of Rhodomicrobium vanielii do not excrete glycollate when gassed anaerobically with nitrogen plus carbon dioxide, although the addition of alpha-hydroxy-2-pyridine methanesulphonate (HPMS) results in the excretion of a trace amount of glycollate. The inclucion of low amounts of oxygen in this gas mixture results in marked glycollate excretion, higher rates occurring in the presence of HPMS. 2. Cell extracts of Rhodomicrobium vannielii, and also of Rhodospirillum rubrum, which excretes glycollate only under aerobic conditions in the light, catalyze the formation of glycollate from phosphoglycollate and also the oxidation of glycollate to glyoxylate."} {"id": "PMID:168832", "title": "Mutants of Serratia marcescens lacking cyclic nucleotide phosphodiesterase activity and requiring cyclic 3',5'-AMP for the utilization of various carbohydrates.", "content": "Adenine requiring mutants of Serratia marcescens SM-6-F'lac+ have been found to grow well in minimal-glucose medium solely supplemented with cAMP. From one of these ade strains double mutants (called ade cpd) were isolated which could no longer utilize cAMP but which still grew on 5'AMP. Dialyzed cell extracts (soluble fraction) of the double mutants, assayed for cAMP phosphodiesterase, were unable to hydrolyze cAMP whereas cell extracts of the parental strains yielded 5'AMP at a rate of 1.6-2.0 mumoles min-1 mg-1 protein. The loss of the phosphodiesterase activity in S. marcescens cpd W 1181 did not cause an accumulation of large amounts of cAMP as was found for the diesterase-negative mutant AB257pc-1 of Escherichia coli. The induced synthesis of beta-galactosidase in mutant cpd W 1181 showed about the same sensitivity to transient and permanent catabolite (glucose) repression as the corresponding cpd+ strain. Starting from S. marcescens cpd W 1182 three independent double mutants (called cpd cya) were isolated which required exogenous cAMP for utilizing various carbohydrates as carbon source, for motility and for the formation of extracellular lipase and the red pigment prodigiosine. The intracellular concentration of cAMP in these mutants, grown in nutrient broth, was 40-60% of that of the parental strain which is about 4 x 10(-4) M. However, the adenylate cyclase in cell extracts of the mutants W 1237 and W 1270 was like that of the corresponding cya+ strain (about 2 x 10(-2) mumoles min-1 mg-1 protein).", "contents": "Mutants of Serratia marcescens lacking cyclic nucleotide phosphodiesterase activity and requiring cyclic 3',5'-AMP for the utilization of various carbohydrates. Adenine requiring mutants of Serratia marcescens SM-6-F'lac+ have been found to grow well in minimal-glucose medium solely supplemented with cAMP. From one of these ade strains double mutants (called ade cpd) were isolated which could no longer utilize cAMP but which still grew on 5'AMP. Dialyzed cell extracts (soluble fraction) of the double mutants, assayed for cAMP phosphodiesterase, were unable to hydrolyze cAMP whereas cell extracts of the parental strains yielded 5'AMP at a rate of 1.6-2.0 mumoles min-1 mg-1 protein. The loss of the phosphodiesterase activity in S. marcescens cpd W 1181 did not cause an accumulation of large amounts of cAMP as was found for the diesterase-negative mutant AB257pc-1 of Escherichia coli. The induced synthesis of beta-galactosidase in mutant cpd W 1181 showed about the same sensitivity to transient and permanent catabolite (glucose) repression as the corresponding cpd+ strain. Starting from S. marcescens cpd W 1182 three independent double mutants (called cpd cya) were isolated which required exogenous cAMP for utilizing various carbohydrates as carbon source, for motility and for the formation of extracellular lipase and the red pigment prodigiosine. The intracellular concentration of cAMP in these mutants, grown in nutrient broth, was 40-60% of that of the parental strain which is about 4 x 10(-4) M. However, the adenylate cyclase in cell extracts of the mutants W 1237 and W 1270 was like that of the corresponding cya+ strain (about 2 x 10(-2) mumoles min-1 mg-1 protein)."} {"id": "PMID:168833", "title": "[Exerimental study on cancerogenic activity of Propanol-1, 2-Methylpropanol-1 and 3-Methylbutanol-1 (author's transl)].", "content": "By using Propanol-1, 2-Methylpropanol-1 cancerogenic, hepatotoxic and haematotoxic effects could pointed out by an experimental study with rats. These high alcoholics are frequently used in the chemical industry but they are also essential parts of most of the alcoholic beverages. It is recommended to define safety limit.", "contents": "[Exerimental study on cancerogenic activity of Propanol-1, 2-Methylpropanol-1 and 3-Methylbutanol-1 (author's transl)]. By using Propanol-1, 2-Methylpropanol-1 cancerogenic, hepatotoxic and haematotoxic effects could pointed out by an experimental study with rats. These high alcoholics are frequently used in the chemical industry but they are also essential parts of most of the alcoholic beverages. It is recommended to define safety limit."} {"id": "PMID:168834", "title": "[The tumor-tetanus assay--experimental studies on the biological differentiation between carcinogenesis and organ regeneration of the rat (author's transl)].", "content": "The characteristic clostridial growth which is testable, after systemic administration of tetanus spores, as a positive tumour tetanus - correlation, was manifested by a highly selective tetanus lethality of rats with progressive hepatomas following induction with dimethylaminoazobenzene and diethylnitrosamine, respectively, as well as with methylcholanthren-induced fibrosarcomas of the rat. Control tumours with transplantable Walker carcinoma cells anYoshida sarcoma cells also developed tetanus most frequently whereas healthy tumour-free rats did not show any signs of tetanus for the period of observation. There was strict time-dose-relationship of tetanus after partial hepatectomy, using the same injection technique of the spores, in sofar as the spores injected 24 hours postoperatively caused tetanus as opposed to the completely negative results following spore administration 4 days postoperatively. The mean tetanus survival time of the rats with regeneration of the liver roughly corresponded to that of the wound regeneration assay using pregant rats post partum. The interpretation of these results allows for demonstrating a fairly good agreement between the growth capacity of tumour cells on the one hand and the permanently strong tetanus reactivity on the other, as compared with the time-limited \"take\" and course of tetanus following regeneration of the liver.", "contents": "[The tumor-tetanus assay--experimental studies on the biological differentiation between carcinogenesis and organ regeneration of the rat (author's transl)]. The characteristic clostridial growth which is testable, after systemic administration of tetanus spores, as a positive tumour tetanus - correlation, was manifested by a highly selective tetanus lethality of rats with progressive hepatomas following induction with dimethylaminoazobenzene and diethylnitrosamine, respectively, as well as with methylcholanthren-induced fibrosarcomas of the rat. Control tumours with transplantable Walker carcinoma cells anYoshida sarcoma cells also developed tetanus most frequently whereas healthy tumour-free rats did not show any signs of tetanus for the period of observation. There was strict time-dose-relationship of tetanus after partial hepatectomy, using the same injection technique of the spores, in sofar as the spores injected 24 hours postoperatively caused tetanus as opposed to the completely negative results following spore administration 4 days postoperatively. The mean tetanus survival time of the rats with regeneration of the liver roughly corresponded to that of the wound regeneration assay using pregant rats post partum. The interpretation of these results allows for demonstrating a fairly good agreement between the growth capacity of tumour cells on the one hand and the permanently strong tetanus reactivity on the other, as compared with the time-limited \"take\" and course of tetanus following regeneration of the liver."} {"id": "PMID:168835", "title": "Neurological abnormalities in the leg(s) after use of intraaortic balloon pump: report of six cases.", "content": "Six patients from a group of 39 who survived after treatment with the intraaortic balloon pump (lABP) had significant neurological deficits in one or both legs associated with the use of the lABP. The device was used in a group of 89 patients initially for cardiogenic shock but its use has been expanded for patients having the following conditions: preshock; severe congestive heart failure; refractory angina; and for those undergoing open-heart surgery. The six patients who had neurological sequelae had eight lABP insertions into the thoracic aorta through the femoral artery and had neurological abnormalities and/or electromyographic abnormalities in nine lower extremities ranging from a foot drop to almost total paralysis of the lower extremity. The pathophysiology of the neurological deficit is postulated to be an obstruction to blood flow, or thromboemboli, in the femoral artery.", "contents": "Neurological abnormalities in the leg(s) after use of intraaortic balloon pump: report of six cases. Six patients from a group of 39 who survived after treatment with the intraaortic balloon pump (lABP) had significant neurological deficits in one or both legs associated with the use of the lABP. The device was used in a group of 89 patients initially for cardiogenic shock but its use has been expanded for patients having the following conditions: preshock; severe congestive heart failure; refractory angina; and for those undergoing open-heart surgery. The six patients who had neurological sequelae had eight lABP insertions into the thoracic aorta through the femoral artery and had neurological abnormalities and/or electromyographic abnormalities in nine lower extremities ranging from a foot drop to almost total paralysis of the lower extremity. The pathophysiology of the neurological deficit is postulated to be an obstruction to blood flow, or thromboemboli, in the femoral artery."} {"id": "PMID:168836", "title": "Long thoracic nerve palsy: a follow-up study.", "content": "Twelve patients who had previously been treated for palsy of the long thoracic nerve of Bell and resultant serratus anterior paralysis were examined in a follow-up study designed to determine their extent of recovery and/or residual disability. The patients' histories were reviewed, following which they were recalled for updating of the history and reexamination. It was found that those patients whose lesions were due to acute trauma had only partial or no recovery of serratus function, while those with infectious, toxic, allergic or idiopathic etiologies had partial or complete recovery. The occurrence of a prolonged interval between onset of symptoms and institution of therapy was found to adversely affect prognosis. Among those patients with no recovery of serratus anterior function, some were able to maintain relatively good active motion in the affected shoulder by substituting with the trapezius.", "contents": "Long thoracic nerve palsy: a follow-up study. Twelve patients who had previously been treated for palsy of the long thoracic nerve of Bell and resultant serratus anterior paralysis were examined in a follow-up study designed to determine their extent of recovery and/or residual disability. The patients' histories were reviewed, following which they were recalled for updating of the history and reexamination. It was found that those patients whose lesions were due to acute trauma had only partial or no recovery of serratus function, while those with infectious, toxic, allergic or idiopathic etiologies had partial or complete recovery. The occurrence of a prolonged interval between onset of symptoms and institution of therapy was found to adversely affect prognosis. Among those patients with no recovery of serratus anterior function, some were able to maintain relatively good active motion in the affected shoulder by substituting with the trapezius."} {"id": "PMID:168837", "title": "Implications of suspicious findings in breast cancer screening.", "content": "Breast cancer screening, performed on asymptomatic women over 35 years of age, has identified 32 breast cancers in 30 of 4,500 women screened. Screening included a physical examination by trained technologists, thermography, and xeromammography. This represents 26 percent of the biopsies performed (116). Results of xerommammography were suspicious in 24 cases (80 percent), and results of physical examination were suspicious in 11 (37 percent). Only six were suspicious by both methods, with one other having changes that were considered benign. Fourteen (44 percent) were microinvasive or noninvasive. Only two (6 percent) had axillary metastases. Breast cancer detected by screening is in its \"early\" stages and is usually well localized. Operative management, including removal of the entire breast, has a significant potential for cure. Thirty patients with changes considered suspicious have not yet had biopsies. Improved overall survival depends on appropriate management of all patients screened.", "contents": "Implications of suspicious findings in breast cancer screening. Breast cancer screening, performed on asymptomatic women over 35 years of age, has identified 32 breast cancers in 30 of 4,500 women screened. Screening included a physical examination by trained technologists, thermography, and xeromammography. This represents 26 percent of the biopsies performed (116). Results of xerommammography were suspicious in 24 cases (80 percent), and results of physical examination were suspicious in 11 (37 percent). Only six were suspicious by both methods, with one other having changes that were considered benign. Fourteen (44 percent) were microinvasive or noninvasive. Only two (6 percent) had axillary metastases. Breast cancer detected by screening is in its \"early\" stages and is usually well localized. Operative management, including removal of the entire breast, has a significant potential for cure. Thirty patients with changes considered suspicious have not yet had biopsies. Improved overall survival depends on appropriate management of all patients screened."} {"id": "PMID:168838", "title": "In vitro evaluation of inhibitors of platelet release and aggregation.", "content": "In order to determine which drugs would be most effective as inhibitors of platelet release and aggregation, in vitro release reactions and platelet aggregometry were used to evaluate aspirin, dipyridamole, sulfinpyrazone, flurbiprofen, low molecular weight dextran (dextran 40), prostaglandin E1 (PGE1), apyrase, and adenosine. Adenosine diphosphate-induced aggregation was most effectively inhibited by PGF1, sulfinpyrazone, and dipyridamole. The latter had to be used in large doses. Collagen and epinephrine-induced release and aggregation were inhibited by the same drugs as well as by aspirin and apyrase. Antihynocyte globulin (ATG)-induced release and aggregation could only be partially blocked by these agents. In vitro studies suggest that sulfinpyrazone is one of the most effective of platelet inhibitors currently available for clinical testing.", "contents": "In vitro evaluation of inhibitors of platelet release and aggregation. In order to determine which drugs would be most effective as inhibitors of platelet release and aggregation, in vitro release reactions and platelet aggregometry were used to evaluate aspirin, dipyridamole, sulfinpyrazone, flurbiprofen, low molecular weight dextran (dextran 40), prostaglandin E1 (PGE1), apyrase, and adenosine. Adenosine diphosphate-induced aggregation was most effectively inhibited by PGF1, sulfinpyrazone, and dipyridamole. The latter had to be used in large doses. Collagen and epinephrine-induced release and aggregation were inhibited by the same drugs as well as by aspirin and apyrase. Antihynocyte globulin (ATG)-induced release and aggregation could only be partially blocked by these agents. In vitro studies suggest that sulfinpyrazone is one of the most effective of platelet inhibitors currently available for clinical testing."} {"id": "PMID:168840", "title": "Guanidine and neuromuscular transmission. I. Effect on transmitter release occurring spontaneously and in response to single nerve stimuli.", "content": "The effect of guanidine on neuromuscular transmission was studied in human intercostal muscle and mouse diaphragm preparations in vitro. Guanidine greatly increased the number of acetylcholine (ACh) quanta released by a single motor nerve action potential. This effect of guanidine was greater at junctions with a low quantum content. The spontaneous release of ACh quanta was not substantially changed by guanidine. No change was found in the postsynaptic sensitivity to ACh released from the motor nerve or iontophoretically applied to the muscle fiber. Effects of the drug had slow onset and were very long-lasting and resistant to wash.", "contents": "Guanidine and neuromuscular transmission. I. Effect on transmitter release occurring spontaneously and in response to single nerve stimuli. The effect of guanidine on neuromuscular transmission was studied in human intercostal muscle and mouse diaphragm preparations in vitro. Guanidine greatly increased the number of acetylcholine (ACh) quanta released by a single motor nerve action potential. This effect of guanidine was greater at junctions with a low quantum content. The spontaneous release of ACh quanta was not substantially changed by guanidine. No change was found in the postsynaptic sensitivity to ACh released from the motor nerve or iontophoretically applied to the muscle fiber. Effects of the drug had slow onset and were very long-lasting and resistant to wash."} {"id": "PMID:168841", "title": "Guanidine and neuromuscular transmission. II. Effect on transmitter release in response to repetitive nerve stimulation.", "content": "The effect of guanidine on the neuromuscular transmission in human intercostal and mouse diaphragm muscle in vitro during repetitive nerve stimulation was studied. The drug greatly increased the release of acetylcholine (ACh) quanta by nerve impulses at low frequencies of nerve stimulation and at the beginning of tetani at high frequencies of stimulation. The effect was shown to be produced by an increase in fractional release from an unchanged store of ACh quanta available fro immediate release. This seems to explain why guanidine has a poor therapeutic effect in myasthenia gravis but a good effect in the myasthenic syndrome.", "contents": "Guanidine and neuromuscular transmission. II. Effect on transmitter release in response to repetitive nerve stimulation. The effect of guanidine on the neuromuscular transmission in human intercostal and mouse diaphragm muscle in vitro during repetitive nerve stimulation was studied. The drug greatly increased the release of acetylcholine (ACh) quanta by nerve impulses at low frequencies of nerve stimulation and at the beginning of tetani at high frequencies of stimulation. The effect was shown to be produced by an increase in fractional release from an unchanged store of ACh quanta available fro immediate release. This seems to explain why guanidine has a poor therapeutic effect in myasthenia gravis but a good effect in the myasthenic syndrome."} {"id": "PMID:168842", "title": "Axonal degeneration in sodium cyanate-induced neuropathy.", "content": "Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter.", "contents": "Axonal degeneration in sodium cyanate-induced neuropathy. Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter."} {"id": "PMID:168843", "title": "Phenytoin and membrane fluidity in myotonic dystrophy.", "content": "Electron spin resonance spectroscopy was used to substantiate the presence of a membrane defect in myotonic erythrocytes. There was increased membrane fluidity and decreased polarity in myotonic membranes. Phenytoin (formerly diphenylhydantoin) \"normalizes\" fluidity differences in spectra derived from myotonic erythrocytes but has no significant effect on normal spectra. These experiments demonstrate the applicability of biophysical methods to human erythrocyte membranes and support the concept of a membrane defect in myotonic dystrophy that does not have a primary myopathic, neuropathic, or vascular cause.", "contents": "Phenytoin and membrane fluidity in myotonic dystrophy. Electron spin resonance spectroscopy was used to substantiate the presence of a membrane defect in myotonic erythrocytes. There was increased membrane fluidity and decreased polarity in myotonic membranes. Phenytoin (formerly diphenylhydantoin) \"normalizes\" fluidity differences in spectra derived from myotonic erythrocytes but has no significant effect on normal spectra. These experiments demonstrate the applicability of biophysical methods to human erythrocyte membranes and support the concept of a membrane defect in myotonic dystrophy that does not have a primary myopathic, neuropathic, or vascular cause."} {"id": "PMID:168844", "title": "Phosphodiesterase inhibitors and cerebral vasospasm.", "content": "Experimental cerebral vasospasm was studied in cat and monkey models. In the cat, the basilar artery was exposed by a transclival approach and spasm induced by the application of blood to the vessel. In the monkey, spasm was produced by injecting blood into the subarachnoid space. Vessel size was determined in the cat by direct observation and, in the monkey, by cerebral angiography. Several agents known to alter the synthsis and degradation of cyclic adenosine monophosphate (AMP) were used to modity the vasospasm produced. Isoproterenol (Norisodrine) and aminophyline were effective in reversing cerebral vasospasm when applied topically and when administered parenterally. It is suggested that manipulation of the cyclic AMP pathways may be an effective method of controlling cerebral vasospasm.", "contents": "Phosphodiesterase inhibitors and cerebral vasospasm. Experimental cerebral vasospasm was studied in cat and monkey models. In the cat, the basilar artery was exposed by a transclival approach and spasm induced by the application of blood to the vessel. In the monkey, spasm was produced by injecting blood into the subarachnoid space. Vessel size was determined in the cat by direct observation and, in the monkey, by cerebral angiography. Several agents known to alter the synthsis and degradation of cyclic adenosine monophosphate (AMP) were used to modity the vasospasm produced. Isoproterenol (Norisodrine) and aminophyline were effective in reversing cerebral vasospasm when applied topically and when administered parenterally. It is suggested that manipulation of the cyclic AMP pathways may be an effective method of controlling cerebral vasospasm."} {"id": "PMID:168847", "title": "Colloid carcinoma arising in an anal fistula: case report with a brief review of the literature.", "content": "Malignant change in an anal fistula is an extremely rare but an important and dangerous complication. Less than 75 cases have been described in the English and Scandinavian literature. We now report a case of colloid carcinoma arising in an anal fistula because of its rarity and other interesting features.", "contents": "Colloid carcinoma arising in an anal fistula: case report with a brief review of the literature. Malignant change in an anal fistula is an extremely rare but an important and dangerous complication. Less than 75 cases have been described in the English and Scandinavian literature. We now report a case of colloid carcinoma arising in an anal fistula because of its rarity and other interesting features."} {"id": "PMID:168849", "title": "Two levels of genetic resistance to lymphoid leukosis.", "content": "Two levels of genetic resistance to lymphoid leukosis are recognized: 1) cellular resistance to virus infection; and 2) resistance to tumor development in leukosis-virus-infected birds. Resistance to infection is simply inherited but is very specific for the subgroup of virus. Inheritance of resistance to tumor development is more complex but appears to be less subgroup-specific. A breeder may wish to select for resistance to infection of virus eradication is the goal. If his goal is the reduction of lymphoid tumors, with virus infection not important, he may choose to select for resistance to tumor development.", "contents": "Two levels of genetic resistance to lymphoid leukosis. Two levels of genetic resistance to lymphoid leukosis are recognized: 1) cellular resistance to virus infection; and 2) resistance to tumor development in leukosis-virus-infected birds. Resistance to infection is simply inherited but is very specific for the subgroup of virus. Inheritance of resistance to tumor development is more complex but appears to be less subgroup-specific. A breeder may wish to select for resistance to infection of virus eradication is the goal. If his goal is the reduction of lymphoid tumors, with virus infection not important, he may choose to select for resistance to tumor development."} {"id": "PMID:168850", "title": "Phenotypic mixing test to detect and assay avian leukosis viruses.", "content": "A phenotypic mixing (PM) test for detecting and assaying avian leukosis viruses (ALV) of the A, B, C, and D subgroups is described. An ALV and Rous sarcoma virus RSV-0) are phenotypically mixed by co-cultivating on C/O (cells susceptible to all subgroups of ALV) cells for a certain period. Then the RSV with the new virus property is assayed on C/E cells (cells resistant to infection with subgroup E leukosis/sarcoma viruses). The test is relatively simple and rapid, and its results are unequivocal. It is as sensitive as the more lengthy complement-fixation test (COFAL). The system is suitable for detecting avian leukosis viruses in samples such as heparinized blood, plasma, and embryo extracts.", "contents": "Phenotypic mixing test to detect and assay avian leukosis viruses. A phenotypic mixing (PM) test for detecting and assaying avian leukosis viruses (ALV) of the A, B, C, and D subgroups is described. An ALV and Rous sarcoma virus RSV-0) are phenotypically mixed by co-cultivating on C/O (cells susceptible to all subgroups of ALV) cells for a certain period. Then the RSV with the new virus property is assayed on C/E cells (cells resistant to infection with subgroup E leukosis/sarcoma viruses). The test is relatively simple and rapid, and its results are unequivocal. It is as sensitive as the more lengthy complement-fixation test (COFAL). The system is suitable for detecting avian leukosis viruses in samples such as heparinized blood, plasma, and embryo extracts."} {"id": "PMID:168851", "title": "Two new isolants of infectious bronchitis virus with polyvalent immunogenicity.", "content": "The immunizing capacity of two new field isolants of avian infectious bronchitis virus (IBV) was tested in vivo. Chickens vaccinated with either isolant resisted challenge with 6 serotypes of IBV, including some of the types most commonly isolated from chickens. The two new isolants, identified herein as California \"G\" and California \"S,\" appear to be immunologically different from each other and from the other 6 types tested. The polyvalent immunogenicity of both G and S is noteworthy, and potentially a very promising characteristic for the development of effective vaccines. The immunogenicity is slightly better for G than for S, but both are still pathogenic for chickens. Therefore, they should be attenuated before being used as vaccines.", "contents": "Two new isolants of infectious bronchitis virus with polyvalent immunogenicity. The immunizing capacity of two new field isolants of avian infectious bronchitis virus (IBV) was tested in vivo. Chickens vaccinated with either isolant resisted challenge with 6 serotypes of IBV, including some of the types most commonly isolated from chickens. The two new isolants, identified herein as California \"G\" and California \"S,\" appear to be immunologically different from each other and from the other 6 types tested. The polyvalent immunogenicity of both G and S is noteworthy, and potentially a very promising characteristic for the development of effective vaccines. The immunogenicity is slightly better for G than for S, but both are still pathogenic for chickens. Therefore, they should be attenuated before being used as vaccines."} {"id": "PMID:168856", "title": "Variations in the activTY OF SOME BRAIN AND PLASMA ENZYMES UNDER THE INFLUENCE OF +Gz acceleration.", "content": "The present paper refers to the activity of some enzymes associated with the cellular cytomembranes in the plasma and brain of guinea pigs exposed to the action of repeated +10Gz acceleration. Immediately after the last run, diminution of enzymatic activity in the brain supernate ran parralel to a rise in plasma enzymatic activity. Variations in enzymatic activity suggested the liberation of enzymes connected with the neuronal organelles, perhaps consequent to alterations in the permeability or structure of the neuronal cytomembranes. These alterations might also be interpreted as being accompanied by permeabilization of the blood-brain barrier, with release of enzymes from the neuronal structures into the plasma. Changes in the permeability of the neuronal membranes might be attributed to several factors: cerebral hypoxia following the hemodynamic and ventilation alterations induced by hypergravitation, the influence upon the membrane permeability of hormones released in excess under the stress of acceleration, and the strain to which the central nervous system neurones are subjected by the multitude of afferent impulses with a starting point in the various types of receptors stimulated by hypergravitation.", "contents": "Variations in the activTY OF SOME BRAIN AND PLASMA ENZYMES UNDER THE INFLUENCE OF +Gz acceleration. The present paper refers to the activity of some enzymes associated with the cellular cytomembranes in the plasma and brain of guinea pigs exposed to the action of repeated +10Gz acceleration. Immediately after the last run, diminution of enzymatic activity in the brain supernate ran parralel to a rise in plasma enzymatic activity. Variations in enzymatic activity suggested the liberation of enzymes connected with the neuronal organelles, perhaps consequent to alterations in the permeability or structure of the neuronal cytomembranes. These alterations might also be interpreted as being accompanied by permeabilization of the blood-brain barrier, with release of enzymes from the neuronal structures into the plasma. Changes in the permeability of the neuronal membranes might be attributed to several factors: cerebral hypoxia following the hemodynamic and ventilation alterations induced by hypergravitation, the influence upon the membrane permeability of hormones released in excess under the stress of acceleration, and the strain to which the central nervous system neurones are subjected by the multitude of afferent impulses with a starting point in the various types of receptors stimulated by hypergravitation."} {"id": "PMID:168852", "title": "Identification of infectious bronchitis virus by interference with the B-1 isolant of Newcastle disease virus. Waxing and waning of interference.", "content": "The Massachusetts and the Connecticut types of infectious bronchitis virus (IBV) were identified by interference in embryonating chicken eggs (ECE) with the production of hemagglutinin by the B-1 isolant of Newcastle disease virus (NDV). This interference test appears to be specific because the above interference was eliminated by adding type-specific anti-IBV serum to the IBV-NDV system; however, interference was not detectable when fowlpox virus (FPV) and infectious laryngotracheitis virus (LTV) were substituted for IBV. Specificity of the interference test was dependent upon a system involving IBV, NDV, FPV, and LTV. The test can be done in 3 days and requires minimum laboratory facilities. Most of the experiments were done with the Massachusetts type of IBV. Only a few were with the Connecticut type. The interfering action of the above two types of IBV over the B-1 isolant of NDV waxed between the 24th and 54th hr after inoculation of NDV; it was waning at the 54th-60th hr postinoculation and was undetectable by the 66th-72nd hr.", "contents": "Identification of infectious bronchitis virus by interference with the B-1 isolant of Newcastle disease virus. Waxing and waning of interference. The Massachusetts and the Connecticut types of infectious bronchitis virus (IBV) were identified by interference in embryonating chicken eggs (ECE) with the production of hemagglutinin by the B-1 isolant of Newcastle disease virus (NDV). This interference test appears to be specific because the above interference was eliminated by adding type-specific anti-IBV serum to the IBV-NDV system; however, interference was not detectable when fowlpox virus (FPV) and infectious laryngotracheitis virus (LTV) were substituted for IBV. Specificity of the interference test was dependent upon a system involving IBV, NDV, FPV, and LTV. The test can be done in 3 days and requires minimum laboratory facilities. Most of the experiments were done with the Massachusetts type of IBV. Only a few were with the Connecticut type. The interfering action of the above two types of IBV over the B-1 isolant of NDV waxed between the 24th and 54th hr after inoculation of NDV; it was waning at the 54th-60th hr postinoculation and was undetectable by the 66th-72nd hr."} {"id": "PMID:168853", "title": "Immunity levels against avian encephalomyelitis in vaccinated poultry breeder flocks in Maine.", "content": "Four commercial poultry breeder flocks that were vaccinated under field conditions against avian encephalomyelitis (AE) with commercial live or inactivated vaccine were monitored periodically by virus-neutralization testing of blood serum samples and by challenge of their progeny eggs and chicks. The history of the flocks and results of the tests indicate that field exposure might occur during the laying period, thereby boosting immunity titers without causing clinical AE in the progeny chicks. The data also indicate field exposure of certain flocks before AE vaccination.", "contents": "Immunity levels against avian encephalomyelitis in vaccinated poultry breeder flocks in Maine. Four commercial poultry breeder flocks that were vaccinated under field conditions against avian encephalomyelitis (AE) with commercial live or inactivated vaccine were monitored periodically by virus-neutralization testing of blood serum samples and by challenge of their progeny eggs and chicks. The history of the flocks and results of the tests indicate that field exposure might occur during the laying period, thereby boosting immunity titers without causing clinical AE in the progeny chicks. The data also indicate field exposure of certain flocks before AE vaccination."} {"id": "PMID:168854", "title": "The addition of fowlpox and pigeon pox vaccine to Marek's vaccine for broilers.", "content": "Laboratory and field studies indicated that a cell-culture fowlpox vaccine was effective and safe when administered subcutaneously to day-old broiler chicks in combination with cell-associated Marek's vaccine without compromising the latter. Pox vaccines of chick embryo origin evaluated similarly provided excellent protection, although they caused local musculature swelling when injected into muscle rather than under the skin. No muscle swelling followed improper vaccination with the cell-culture fowlpox vaccine.", "contents": "The addition of fowlpox and pigeon pox vaccine to Marek's vaccine for broilers. Laboratory and field studies indicated that a cell-culture fowlpox vaccine was effective and safe when administered subcutaneously to day-old broiler chicks in combination with cell-associated Marek's vaccine without compromising the latter. Pox vaccines of chick embryo origin evaluated similarly provided excellent protection, although they caused local musculature swelling when injected into muscle rather than under the skin. No muscle swelling followed improper vaccination with the cell-culture fowlpox vaccine."} {"id": "PMID:168855", "title": "Occurrence of duck virus enteritis (duck plague) in Pennsylvania, 1968-74.", "content": "During the 7-year period 1968-74 cases of duck virus enteritis (duck plague) were diagnosed in waterfowl in Pennsylvania. Muscovy ducks were affected in 8 cases, geese in 3 cases, and mallard ducks in 1 case. In 5 of these cases either domestic or wild ducks were closely associated with infected waterfowl but were unaffected.", "contents": "Occurrence of duck virus enteritis (duck plague) in Pennsylvania, 1968-74. During the 7-year period 1968-74 cases of duck virus enteritis (duck plague) were diagnosed in waterfowl in Pennsylvania. Muscovy ducks were affected in 8 cases, geese in 3 cases, and mallard ducks in 1 case. In 5 of these cases either domestic or wild ducks were closely associated with infected waterfowl but were unaffected."} {"id": "PMID:168861", "title": "Localization and quantitation of EBV-associated nuclear antigen (EBNA) in Raji cells.", "content": "Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was localized to chromatin fibers of Raji cells. When EBNA was labeled with the horseradish-peroxidase technique of Sternberger a strong reaction covered most fiber surfaces as observed by electron microscopy. The dry mass of Raji chromatin increased after exposure to both EBV-positive and -negative serum, but the increase was significantly larger in the material treated with positive serum.", "contents": "Localization and quantitation of EBV-associated nuclear antigen (EBNA) in Raji cells. Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was localized to chromatin fibers of Raji cells. When EBNA was labeled with the horseradish-peroxidase technique of Sternberger a strong reaction covered most fiber surfaces as observed by electron microscopy. The dry mass of Raji chromatin increased after exposure to both EBV-positive and -negative serum, but the increase was significantly larger in the material treated with positive serum."} {"id": "PMID:168862", "title": "Biogenesis of intranuclear lead-protein inclusions in mouse kidney.", "content": "A single dose of lead (5 mug/g body weight), given as lead acetate by intracardiac injection, produces, within 8 hours, characteristic fibrillar intranuclear and intracytoplasmic inclusions in proximal tubular epithelial cells in mouse kidneys; after a dose of 40 mug/g body weight, such inclusion appeared within 6 hours. Their development was completely prevented by cycloheximide (one or more intraperitoneal injections of 20 mug/g body weight). The development of intranuclear inclusions was also noted in tubular epithelial cells explanted from normal mice and grown in vitro for 15 hours in a medium containing 20 mug lead/ml. Thus, the development of the characteristic fibrillar inclusion bodies depends upon de novo synthesis of inclusion body protein, induced by lead.", "contents": "Biogenesis of intranuclear lead-protein inclusions in mouse kidney. A single dose of lead (5 mug/g body weight), given as lead acetate by intracardiac injection, produces, within 8 hours, characteristic fibrillar intranuclear and intracytoplasmic inclusions in proximal tubular epithelial cells in mouse kidneys; after a dose of 40 mug/g body weight, such inclusion appeared within 6 hours. Their development was completely prevented by cycloheximide (one or more intraperitoneal injections of 20 mug/g body weight). The development of intranuclear inclusions was also noted in tubular epithelial cells explanted from normal mice and grown in vitro for 15 hours in a medium containing 20 mug lead/ml. Thus, the development of the characteristic fibrillar inclusion bodies depends upon de novo synthesis of inclusion body protein, induced by lead."} {"id": "PMID:168864", "title": "Multiple protein kinases from human lymphocytes. Identification enzymes phosphorylating exogenous histon and casein.", "content": "1. Cell-free lysates of human peripheral blood lymphocytes contained two casein kinase activities and two histone kinase activities, which could be separated by chromatography on DEAE-Sephadex. 2. Neither of the casein kinase activities were stimulated by cyclic AMP. The major activity was eluted from DEAE-Sephadex between 0.4 and 0.45M-KCl, had a molecular weight of approx. 130,000 (sucrose density gradients) and was stimulated by KCl (maximum 150mM). It also formed higher-molecular-weight aggregates when centrifuged in sucrose gradients containing 150mM-KCl. The minor activity was not retained by DEAE-Sephadex, had a molecular weight of approx. 50,000 and was not stimulated by KCl. 3. The major histone kinase activity was stimulated by cyclic AMP and was eluted from the DEAE-Sephadex column between 0.05 and 0.2M-KCl. The other activity was not stimulated by cyclic AMP and was insensitive to the rabbit muscle protein kinase inhibitor. 4. Evidence was obtained suggesting that the lymphocyte casein kinases were located primarily in the nuclei.", "contents": "Multiple protein kinases from human lymphocytes. Identification enzymes phosphorylating exogenous histon and casein. 1. Cell-free lysates of human peripheral blood lymphocytes contained two casein kinase activities and two histone kinase activities, which could be separated by chromatography on DEAE-Sephadex. 2. Neither of the casein kinase activities were stimulated by cyclic AMP. The major activity was eluted from DEAE-Sephadex between 0.4 and 0.45M-KCl, had a molecular weight of approx. 130,000 (sucrose density gradients) and was stimulated by KCl (maximum 150mM). It also formed higher-molecular-weight aggregates when centrifuged in sucrose gradients containing 150mM-KCl. The minor activity was not retained by DEAE-Sephadex, had a molecular weight of approx. 50,000 and was not stimulated by KCl. 3. The major histone kinase activity was stimulated by cyclic AMP and was eluted from the DEAE-Sephadex column between 0.05 and 0.2M-KCl. The other activity was not stimulated by cyclic AMP and was insensitive to the rabbit muscle protein kinase inhibitor. 4. Evidence was obtained suggesting that the lymphocyte casein kinases were located primarily in the nuclei."} {"id": "PMID:168865", "title": "Isolation and chemical characterization of collagen in bovine pulmonary tissues.", "content": "1. The contents of the fibrous proteins collagen and elastin in the pleural and parenchymal regions of bovine lungs were determined. The collagen content was approx. 70% (g/100g of salt-extracted defatted powder) in each tissue, and the elastin content was 28% in pleura and 13.5% in parenchyma. 2. Purification of the insoluble collagen from the pleura and parenchyma of bovine lungs by various methods was attempted. The collagen fractions isolated after incubation of the pulmonary tissues with the proteolytic enzymes collagenase (\"collagenase-soluble\" fraction) or pancreatic elastase (\"elastase-insoluble\" fraction) each contained approx. 87% of the total collagen initially present. 3. Both collagen fractions were chemically analysed for their amino acid and carbohydrate contents and were found to be similar to those of the intact interstitial collagens isolated from skin, bone and tendon. 4. The contents of the two aldimine cross-linking compounds, dehydrohydroxylysinonorleucine and dehydrodihydroxylysinonorleucine, were determined in the bovine pulmonary collagen fractions, and were found to decrease with increasing age of the animals, and were similar to the values found in intact collagens from bone and tendon.", "contents": "Isolation and chemical characterization of collagen in bovine pulmonary tissues. 1. The contents of the fibrous proteins collagen and elastin in the pleural and parenchymal regions of bovine lungs were determined. The collagen content was approx. 70% (g/100g of salt-extracted defatted powder) in each tissue, and the elastin content was 28% in pleura and 13.5% in parenchyma. 2. Purification of the insoluble collagen from the pleura and parenchyma of bovine lungs by various methods was attempted. The collagen fractions isolated after incubation of the pulmonary tissues with the proteolytic enzymes collagenase (\"collagenase-soluble\" fraction) or pancreatic elastase (\"elastase-insoluble\" fraction) each contained approx. 87% of the total collagen initially present. 3. Both collagen fractions were chemically analysed for their amino acid and carbohydrate contents and were found to be similar to those of the intact interstitial collagens isolated from skin, bone and tendon. 4. The contents of the two aldimine cross-linking compounds, dehydrohydroxylysinonorleucine and dehydrodihydroxylysinonorleucine, were determined in the bovine pulmonary collagen fractions, and were found to decrease with increasing age of the animals, and were similar to the values found in intact collagens from bone and tendon."} {"id": "PMID:168866", "title": "Decay of oxyperoxidase and oxygen radicals; a possible role for myeloperoxidase.", "content": "The formation of superoxide anion during the decay of oxyperoxidase to ferric peroxidase was detected by using a spectrophotometric assay based on the use of adrenaline. The finding that peroxidase is a potential source of superoxide suggests a possible role for myeloperoxidase in leucocytes.", "contents": "Decay of oxyperoxidase and oxygen radicals; a possible role for myeloperoxidase. The formation of superoxide anion during the decay of oxyperoxidase to ferric peroxidase was detected by using a spectrophotometric assay based on the use of adrenaline. The finding that peroxidase is a potential source of superoxide suggests a possible role for myeloperoxidase in leucocytes."} {"id": "PMID:168867", "title": "Electron transfer between azurin and cytochrone c-551 from Pseudomonas aeruginosa.", "content": "The electron-transfer reaction between azurin and cytochrome c1 isolated from Pseudomonas aeruginosa was investigated by rapid-reaction techniques. Temperture-jump studies clearly reveal two chemical relaxations, the amplitudes of which have ikentical spectral distributions, but relaxation times show different dependencies on reactant concentrations. Stopped experiments also showed complex kinetics. A model is proposed which is consistent with the kinetic and equilibrium data obtained. The central feature of this model is the proposal that two intercenvertible forms of reduced azurin exist in solution, only one of which si able to participate directly in the electron-transfer reaction with cytochrome c-551. Support for the hypothesis that two forms of reduced azurin exist is derived from studies on the electron-transfer reaction between azurin and Pseudomonas cytochrome oxidase. The possible physiological significance of such a situation is discussed.", "contents": "Electron transfer between azurin and cytochrone c-551 from Pseudomonas aeruginosa. The electron-transfer reaction between azurin and cytochrome c1 isolated from Pseudomonas aeruginosa was investigated by rapid-reaction techniques. Temperture-jump studies clearly reveal two chemical relaxations, the amplitudes of which have ikentical spectral distributions, but relaxation times show different dependencies on reactant concentrations. Stopped experiments also showed complex kinetics. A model is proposed which is consistent with the kinetic and equilibrium data obtained. The central feature of this model is the proposal that two intercenvertible forms of reduced azurin exist in solution, only one of which si able to participate directly in the electron-transfer reaction with cytochrome c-551. Support for the hypothesis that two forms of reduced azurin exist is derived from studies on the electron-transfer reaction between azurin and Pseudomonas cytochrome oxidase. The possible physiological significance of such a situation is discussed."} {"id": "PMID:168868", "title": "Phosphotriesters in rat liver deoxyribonucleic acid after the administration of the carcinogen NN-dimethylnitrosamine in vivo.", "content": "After treatment with NN-di[14C]methylnitrosamine, samples of DNA were isolated from rat livers by a conventional phenol procedure and examined for the presence of phosphotriesters. A method of capable of detecting relatively small amounts of 14C-labelled phosphotriesters was developed and used to establish that these products account for 10-12% of the total methylation pattern found after treatment with this agent in vitro. The significance of the presence of phosphotriesters in DNA is discussed.", "contents": "Phosphotriesters in rat liver deoxyribonucleic acid after the administration of the carcinogen NN-dimethylnitrosamine in vivo. After treatment with NN-di[14C]methylnitrosamine, samples of DNA were isolated from rat livers by a conventional phenol procedure and examined for the presence of phosphotriesters. A method of capable of detecting relatively small amounts of 14C-labelled phosphotriesters was developed and used to establish that these products account for 10-12% of the total methylation pattern found after treatment with this agent in vitro. The significance of the presence of phosphotriesters in DNA is discussed."} {"id": "PMID:168869", "title": "The altered specificity of cortisone reductase with certain retroandrostan-3-one substrates.", "content": "The retro steroids 17beta-hydroxy-5beta,9beta,10alpha-androstan-3-one and 5beta,9beta,10alpha-androstane-3,17-dione were good substrates for cortisone reductase in the presence of NADH, and the products corresponded to the respective 3beta-hydroxy compounds, in which the 3beta-hydroxyl group is axial and the absolute configuration is 3S. The analogous natural steroids 17beta-hydroxy-5beta,9alpha,10beta-androstan-3-one and 5beta,9alpha,10beta-androstane-3,17-dione were very poor substrates, and gave the corresponding 3alpha(equatorial,3R)-hydroxy compounds, and, in the latter case, also an appreciable amount of 3beta(axial, 3S)-hydroxy-5beta,9alpha,10beta-androstan-17-one. The natural steroids 17beta-hydroxy-5alpha,9alpha,10beta-androstan-3-one and 5alpha,9alpha,10beta-androstane-3,17-dione were better substrates than the retro steroid 17beta-hydroxy-5alpha,9beta,10alpha-androstan-3-one, but were not such good substrates as the retro steroids 17beta-hydroxy-5beta,9beta,10alpha-androstan-3-one and 5beta,9beta,10alpha-androstane-3,17-dione. Unlike these retro steroid 5beta,9beta,10alpha-androstan-3-ones, the natural steroids 17beta-hydroxy-5alpha,9alpha,10beta-androstan-3-one and 5alpha,9alpha,10beta-androstane-3,17-dione gave the corresponding 3alpha(axial,3R)-hydroxy compounds. The retro steroid 17beta-hydroxy-5alpha,9beta,10alpha-androstan-3-one was not a good substrate, and the product of reaction corresponded to the 3alpha(axial,3R)-hydroxy compound. The nature of substrate recognition by this enzyme is discussed in the light of these structure-activity relationships.", "contents": "The altered specificity of cortisone reductase with certain retroandrostan-3-one substrates. The retro steroids 17beta-hydroxy-5beta,9beta,10alpha-androstan-3-one and 5beta,9beta,10alpha-androstane-3,17-dione were good substrates for cortisone reductase in the presence of NADH, and the products corresponded to the respective 3beta-hydroxy compounds, in which the 3beta-hydroxyl group is axial and the absolute configuration is 3S. The analogous natural steroids 17beta-hydroxy-5beta,9alpha,10beta-androstan-3-one and 5beta,9alpha,10beta-androstane-3,17-dione were very poor substrates, and gave the corresponding 3alpha(equatorial,3R)-hydroxy compounds, and, in the latter case, also an appreciable amount of 3beta(axial, 3S)-hydroxy-5beta,9alpha,10beta-androstan-17-one. The natural steroids 17beta-hydroxy-5alpha,9alpha,10beta-androstan-3-one and 5alpha,9alpha,10beta-androstane-3,17-dione were better substrates than the retro steroid 17beta-hydroxy-5alpha,9beta,10alpha-androstan-3-one, but were not such good substrates as the retro steroids 17beta-hydroxy-5beta,9beta,10alpha-androstan-3-one and 5beta,9beta,10alpha-androstane-3,17-dione. Unlike these retro steroid 5beta,9beta,10alpha-androstan-3-ones, the natural steroids 17beta-hydroxy-5alpha,9alpha,10beta-androstan-3-one and 5alpha,9alpha,10beta-androstane-3,17-dione gave the corresponding 3alpha(axial,3R)-hydroxy compounds. The retro steroid 17beta-hydroxy-5alpha,9beta,10alpha-androstan-3-one was not a good substrate, and the product of reaction corresponded to the 3alpha(axial,3R)-hydroxy compound. The nature of substrate recognition by this enzyme is discussed in the light of these structure-activity relationships."} {"id": "PMID:168870", "title": "Fluorine as a hydroxy analogue. Stereospecific phosphorylation of 2-deosy-2-fluoroglycerol by glucerol kinase.", "content": "Glycerol kinase catalyses the phosphorylation of the symmetrical substrate, 2-dexoy-2-flurooglycerol, by ATP to an asymmetric product, 2-deoxy-2-fluoro-sn-glycerol 3-phosphate. The stereospecificity of the enzymic reaction was extablished by unambiguous chemical synthesis of 2-deoxy-2-fluoro-sn-glycerol labelled with 2H at C-1, followed by glycerol kinase-catalysed phosphorylation and isolation of the labelled phosphate. The configuration of the 2H-labelled phosphate was determined by n.m.r. spectroscopy. This enzymic phosphorylation of 2-dexoy-2-fluoroglycerol is absolutely stereospecific in the same sence as that of glycerol, with fluorine replacing the C-2 hydroxy group. The behaviour of fluorine as a hydroxy analogue in directing the stereospecific course of the enzyme reaction is relevant to the use of the fluorine atom of fluoro analogues of substrate as a reporter group for hydroxy-binding sites of enzymes.", "contents": "Fluorine as a hydroxy analogue. Stereospecific phosphorylation of 2-deosy-2-fluoroglycerol by glucerol kinase. Glycerol kinase catalyses the phosphorylation of the symmetrical substrate, 2-dexoy-2-flurooglycerol, by ATP to an asymmetric product, 2-deoxy-2-fluoro-sn-glycerol 3-phosphate. The stereospecificity of the enzymic reaction was extablished by unambiguous chemical synthesis of 2-deoxy-2-fluoro-sn-glycerol labelled with 2H at C-1, followed by glycerol kinase-catalysed phosphorylation and isolation of the labelled phosphate. The configuration of the 2H-labelled phosphate was determined by n.m.r. spectroscopy. This enzymic phosphorylation of 2-dexoy-2-fluoroglycerol is absolutely stereospecific in the same sence as that of glycerol, with fluorine replacing the C-2 hydroxy group. The behaviour of fluorine as a hydroxy analogue in directing the stereospecific course of the enzyme reaction is relevant to the use of the fluorine atom of fluoro analogues of substrate as a reporter group for hydroxy-binding sites of enzymes."} {"id": "PMID:168871", "title": "Deoxyribonucleic acid-dependent ribonucleic acid polymerases from normal and polyoma-transformed BHK-21/C13 cells.", "content": "DNA-dependent RNA polymerase (EC 2.7.7.6) ACTIVITIES FROM NORMAL BHK-21/C13 cells and from BHK-21/C13 cells transformed by polyoma virus (PYY cells) were solubilized and fractionated on columns of DEAE-Sephadex. Various properties of the A and B enzymes from the two types of cell were compared. 1. The yields of polymerase relative to the DNA content of the nuclear preparations are similar for both cell types. 2. The ionic-strength optima of polymerases A and B are 12.5 mM and 100mM with respect to (NH4)2SO4 for both cell types. 3. The Mn2+/Mg2+ activity ratio (measured at the respective optimum for each cation) for polymerase A from BHK-21/C13 cells was 1.48 and for the polymerase A from PYY cells was 0.55. The corresponding ratios for polymerase B were 10.11 for BHK-21/C13 cells and 22.75 for PYY cells. 4. Minor differences in the ability of the A polymerases to transcribe native and denatured DNA templates were observed; such differences were not apparent when the B polymerases were compared. 5. All the polymerases were inhibited completely by actinomycin D and by rifampicin AF/013, but not markedly so by rifampicin. Alpha-amanitin inhibited polymerase B but not polymerase A.", "contents": "Deoxyribonucleic acid-dependent ribonucleic acid polymerases from normal and polyoma-transformed BHK-21/C13 cells. DNA-dependent RNA polymerase (EC 2.7.7.6) ACTIVITIES FROM NORMAL BHK-21/C13 cells and from BHK-21/C13 cells transformed by polyoma virus (PYY cells) were solubilized and fractionated on columns of DEAE-Sephadex. Various properties of the A and B enzymes from the two types of cell were compared. 1. The yields of polymerase relative to the DNA content of the nuclear preparations are similar for both cell types. 2. The ionic-strength optima of polymerases A and B are 12.5 mM and 100mM with respect to (NH4)2SO4 for both cell types. 3. The Mn2+/Mg2+ activity ratio (measured at the respective optimum for each cation) for polymerase A from BHK-21/C13 cells was 1.48 and for the polymerase A from PYY cells was 0.55. The corresponding ratios for polymerase B were 10.11 for BHK-21/C13 cells and 22.75 for PYY cells. 4. Minor differences in the ability of the A polymerases to transcribe native and denatured DNA templates were observed; such differences were not apparent when the B polymerases were compared. 5. All the polymerases were inhibited completely by actinomycin D and by rifampicin AF/013, but not markedly so by rifampicin. Alpha-amanitin inhibited polymerase B but not polymerase A."} {"id": "PMID:168872", "title": "Evidence for a histidine and a cysteine residue in the substrate-binding site of yeast alcohol dehydrogenase.", "content": "1. Yeast alcohol dehydrogenase (EC 1.1.1.1) is inhibited by stoicheiometric concentrations of diethyl pyrocarbonate. The inhibition is due to the acylation of a single histidine residue/monomer (mol.wt. 36000). 2. Alcohol dehydrogenase is also inhibited by stoicheiometric amounts of 5,5'-dithiobis-(2-nitrobenzoate), owing to the modification of a single cysteine residue/monomer. 3. Native alcohol dehydrogenase binds two molecules of reduced coenzyme/molecule of enzyme (mol.wt. 144000). 4. Modification of a single histidine residue/monomer by treatment with diethyl pyrocarbonate prevents the binding of acetamide in the ternary complex, enzyme-NADH-acetamede, but does not prevent the binding of NADH to the enzyme. 5. Modification of a single cysteine residue/monomer does not prevent the binding of acetamide to the ternary complex. After the modification of two thiol groups/monomer by treatment with 5,5'-dithiobis-(2-nitrobenzoate), the capacity of enzyme to bind coenzyme in the ternary complex was virtually abolished. 6. From the results presented in this paper we conclude that at least one histidine and one cysteine residue are closely associated in the substrate-binding site of alcohol dehydrogenase.", "contents": "Evidence for a histidine and a cysteine residue in the substrate-binding site of yeast alcohol dehydrogenase. 1. Yeast alcohol dehydrogenase (EC 1.1.1.1) is inhibited by stoicheiometric concentrations of diethyl pyrocarbonate. The inhibition is due to the acylation of a single histidine residue/monomer (mol.wt. 36000). 2. Alcohol dehydrogenase is also inhibited by stoicheiometric amounts of 5,5'-dithiobis-(2-nitrobenzoate), owing to the modification of a single cysteine residue/monomer. 3. Native alcohol dehydrogenase binds two molecules of reduced coenzyme/molecule of enzyme (mol.wt. 144000). 4. Modification of a single histidine residue/monomer by treatment with diethyl pyrocarbonate prevents the binding of acetamide in the ternary complex, enzyme-NADH-acetamede, but does not prevent the binding of NADH to the enzyme. 5. Modification of a single cysteine residue/monomer does not prevent the binding of acetamide to the ternary complex. After the modification of two thiol groups/monomer by treatment with 5,5'-dithiobis-(2-nitrobenzoate), the capacity of enzyme to bind coenzyme in the ternary complex was virtually abolished. 6. From the results presented in this paper we conclude that at least one histidine and one cysteine residue are closely associated in the substrate-binding site of alcohol dehydrogenase."} {"id": "PMID:168873", "title": "Biosynthesis of phosphatidylethanolamines and phosphatidylcholines from ethanolamine and choline in rat liver.", "content": "1. The kinetics of phosphatidylcholine and phosphatidylethanolamine synthesis in rat liver were followed 5-60 min after the intraportal injection of [14-C]choline and [3-H]-ethanolamine. 2. At all time-intervals the specific radioactivity of CDP-choline was only about half that of phosphorylcholine. This indicated that CDP-choline was formed at a similar rate from phosphorylcholine and phosphatidylcholines, the latter probably through the reverse reaction of cholinephosphotransferase (EC 2.7.8.2.). In view of recent data obtained from experiments in vitro this implies a significant role for the cholinephosphotransferase reaction in the turnover of molecular species of phosphatidylcholine. 3. The specific radioactivity of CDP-ethanolamine was about twice that of phosphorylethanolamine at all time-intervals studied. This supports a previous suggestion that the liver phosphorylethanolamine pool is subject to compartmentation and shows that there is no rapid equilibration between different pools. In contrast with a recent study, no evidence was found for any significant methylation of phosphoryl-or CDP-ethanolamine to the corresponding choline derivative. 4. Quantitative data on the biosynthesis of molecular species of phosphoLIPIDS via CDP derivatives were calculated according to simple kinetic models. They were in the same range as those calculated from earlier data on precusors incorporated via diacylglycerols. 5. The proportion of radioactive phosphatidylethanolamines appearing in the plasma was approximately ten times lower than that for phosphatidylcholines. No selectivity was observed in the transfer into plasma of different molecular species of phosphatidylethanolamine.", "contents": "Biosynthesis of phosphatidylethanolamines and phosphatidylcholines from ethanolamine and choline in rat liver. 1. The kinetics of phosphatidylcholine and phosphatidylethanolamine synthesis in rat liver were followed 5-60 min after the intraportal injection of [14-C]choline and [3-H]-ethanolamine. 2. At all time-intervals the specific radioactivity of CDP-choline was only about half that of phosphorylcholine. This indicated that CDP-choline was formed at a similar rate from phosphorylcholine and phosphatidylcholines, the latter probably through the reverse reaction of cholinephosphotransferase (EC 2.7.8.2.). In view of recent data obtained from experiments in vitro this implies a significant role for the cholinephosphotransferase reaction in the turnover of molecular species of phosphatidylcholine. 3. The specific radioactivity of CDP-ethanolamine was about twice that of phosphorylethanolamine at all time-intervals studied. This supports a previous suggestion that the liver phosphorylethanolamine pool is subject to compartmentation and shows that there is no rapid equilibration between different pools. In contrast with a recent study, no evidence was found for any significant methylation of phosphoryl-or CDP-ethanolamine to the corresponding choline derivative. 4. Quantitative data on the biosynthesis of molecular species of phosphoLIPIDS via CDP derivatives were calculated according to simple kinetic models. They were in the same range as those calculated from earlier data on precusors incorporated via diacylglycerols. 5. The proportion of radioactive phosphatidylethanolamines appearing in the plasma was approximately ten times lower than that for phosphatidylcholines. No selectivity was observed in the transfer into plasma of different molecular species of phosphatidylethanolamine."} {"id": "PMID:168874", "title": "Evidence against an involvement of cyclic nucleotides in the induction of betacyanin synthesis by cytokinins.", "content": "1. A wide range of purine bases, nucleosides and cyclic nucleotides were shown to induce betacyanin synthesis in Amaranthus seedlings. 2. The induction of pigment by benzyladenine, dibutyryl cyclic AMP or cyclic AMP was not potentiated by aminophylline. Aminophylline was shown to inhibit Amaranthus cyclic AMP phosphodiesterase activity. 4. Incubation of seedlings with aminophylline inhibited the conversion of 6-[G--3H]benzyladenine into presumed 9- and 7-glucosylbenzyladenine. 5. Induction of betacyanin synthesis by 6-benzyladenine or by exposure to red light was not accompanied by changes in the total cyclic AMP content in seedlings. 6. It is concluded that the inducers tested act as cytokinin analogues; no evidence was obtained to support cyclic AMP as an intermediate in the induction process.", "contents": "Evidence against an involvement of cyclic nucleotides in the induction of betacyanin synthesis by cytokinins. 1. A wide range of purine bases, nucleosides and cyclic nucleotides were shown to induce betacyanin synthesis in Amaranthus seedlings. 2. The induction of pigment by benzyladenine, dibutyryl cyclic AMP or cyclic AMP was not potentiated by aminophylline. Aminophylline was shown to inhibit Amaranthus cyclic AMP phosphodiesterase activity. 4. Incubation of seedlings with aminophylline inhibited the conversion of 6-[G--3H]benzyladenine into presumed 9- and 7-glucosylbenzyladenine. 5. Induction of betacyanin synthesis by 6-benzyladenine or by exposure to red light was not accompanied by changes in the total cyclic AMP content in seedlings. 6. It is concluded that the inducers tested act as cytokinin analogues; no evidence was obtained to support cyclic AMP as an intermediate in the induction process."} {"id": "PMID:168875", "title": "Phase transitions in yeast mitochondrial membranes. The effect of temperature on the energies of activation of the respiratory enzymes of Saccharomyces cerevisiae.", "content": "The effect of temperature on the activation energies of mitochondrial enzymes of the yeast Saccharomyces cerevisiae was examined. Non-linear Arrhenius plots with discontinuities in the temperature range 14-19 degrees C and 19-22 degrees C were observed for the respiratory enzymes and mitochondrial ATPase (adenosine triphosphatase) respectively. A straight-line Arrhenius plot was observed for the matrix enzyme, malate dehydrogenase. The activation energies of the enzymes associated with succinate oxidation, namely, succinate oxidase, succinate dehydrogenase and succinate-cytochrome c oxidoreductase, were in the range 60-85kJ/mol above the transition temperature and 90-160kJ/mol below the transition temperature. In contrast, the corresponding enzymes associated with NADH oxidation showed significantly lower activation energies, 20-35kJ/mol above and 40-85kJ/mol below the transition temperature. The discontinuities in the Arrhenius plots were still observed after sonication, treatment with non-ionic detergents or freezing and thawing of the mitochondrial membranes. Discontinuities for cytochrome c oxidase activity were only observed in freshly isolated mitochondria, and no distinct breaks were observed after storage at -20 degrees C. Mitochondrial ATPase activity still showed discontinuities after sonication and freezing and thawing, but a linear plot was observed after treatment with non-ionic detergents. The results indicate that the various enzymes of the respiratory chain are located in a similar lipid macroenvironment within the mitochondrial membrane.", "contents": "Phase transitions in yeast mitochondrial membranes. The effect of temperature on the energies of activation of the respiratory enzymes of Saccharomyces cerevisiae. The effect of temperature on the activation energies of mitochondrial enzymes of the yeast Saccharomyces cerevisiae was examined. Non-linear Arrhenius plots with discontinuities in the temperature range 14-19 degrees C and 19-22 degrees C were observed for the respiratory enzymes and mitochondrial ATPase (adenosine triphosphatase) respectively. A straight-line Arrhenius plot was observed for the matrix enzyme, malate dehydrogenase. The activation energies of the enzymes associated with succinate oxidation, namely, succinate oxidase, succinate dehydrogenase and succinate-cytochrome c oxidoreductase, were in the range 60-85kJ/mol above the transition temperature and 90-160kJ/mol below the transition temperature. In contrast, the corresponding enzymes associated with NADH oxidation showed significantly lower activation energies, 20-35kJ/mol above and 40-85kJ/mol below the transition temperature. The discontinuities in the Arrhenius plots were still observed after sonication, treatment with non-ionic detergents or freezing and thawing of the mitochondrial membranes. Discontinuities for cytochrome c oxidase activity were only observed in freshly isolated mitochondria, and no distinct breaks were observed after storage at -20 degrees C. Mitochondrial ATPase activity still showed discontinuities after sonication and freezing and thawing, but a linear plot was observed after treatment with non-ionic detergents. The results indicate that the various enzymes of the respiratory chain are located in a similar lipid macroenvironment within the mitochondrial membrane."} {"id": "PMID:168876", "title": "The relation between lipid mobility and the specific hormone binding of thyroid membranes.", "content": "1. The specific binding of thyroid-stimulating hormone to isolated human thyroid membranes was examined under a variety of conditions. 2. In phosphate-saline buffer (in the presence of 0.14 M-NaCl) on increasing the temperature the binding of the hormone is increased, the plots of bound/free hormone against temperature showing a distinct break around 30 degrees C. 3. Detailed analysis showed that the increased binding is associated with an increase in the number of binding sites. 4. The motional characteristics of three membrane-bound fluorescent probes, 2-(9-anthroyl)palmitic acid, 12-(9-anthryl)stearic acid and N-1-naphthyl-N-phenylamine, were also examined as a function of temperature by measuring both fluorescence polarizations and lifetimes. 5. The results indicated that the 'fluidity' of membrane lipids also increased with temperature. The temperature-dependence of this property also shows a change at about 30 degrees C. 6. Bivalent cations decreased both membrane fluidity and hormone binding. 7. Similar correlations were found between the binding of adrenocorticotrophic hormone and the fluidity of the plasma membranes obtained from adrenal-cortical cells, with the discontinuity occurring in this case at 23 degrees C. 8. The possibility of lipid mobility being important in controlling hormone-receptor function is discussed.", "contents": "The relation between lipid mobility and the specific hormone binding of thyroid membranes. 1. The specific binding of thyroid-stimulating hormone to isolated human thyroid membranes was examined under a variety of conditions. 2. In phosphate-saline buffer (in the presence of 0.14 M-NaCl) on increasing the temperature the binding of the hormone is increased, the plots of bound/free hormone against temperature showing a distinct break around 30 degrees C. 3. Detailed analysis showed that the increased binding is associated with an increase in the number of binding sites. 4. The motional characteristics of three membrane-bound fluorescent probes, 2-(9-anthroyl)palmitic acid, 12-(9-anthryl)stearic acid and N-1-naphthyl-N-phenylamine, were also examined as a function of temperature by measuring both fluorescence polarizations and lifetimes. 5. The results indicated that the 'fluidity' of membrane lipids also increased with temperature. The temperature-dependence of this property also shows a change at about 30 degrees C. 6. Bivalent cations decreased both membrane fluidity and hormone binding. 7. Similar correlations were found between the binding of adrenocorticotrophic hormone and the fluidity of the plasma membranes obtained from adrenal-cortical cells, with the discontinuity occurring in this case at 23 degrees C. 8. The possibility of lipid mobility being important in controlling hormone-receptor function is discussed."} {"id": "PMID:168877", "title": "Subcellular localization of pulmonary antiotensin-converting enzyme (kininase II).", "content": "Goat antibodies to pig lung angiotensin-converting enzyme (kininase II) were conjugated to microperoxidase. Rat lung tissue, previously incubated with non-immune goat serum, was incubated with the antibody-microperoxidase conjugate and then with H2O2 and 3,3-diaminobenzidine. Electron microscopy revealed reaction product on the plasma membrane and caveolae of endothelial cells, especially those of capillaries and venules. These results support the hypothesis that angiotensin I and bradykinin are metabolized by enzymes on the luminal surface of pulmonary endothelial cells.", "contents": "Subcellular localization of pulmonary antiotensin-converting enzyme (kininase II). Goat antibodies to pig lung angiotensin-converting enzyme (kininase II) were conjugated to microperoxidase. Rat lung tissue, previously incubated with non-immune goat serum, was incubated with the antibody-microperoxidase conjugate and then with H2O2 and 3,3-diaminobenzidine. Electron microscopy revealed reaction product on the plasma membrane and caveolae of endothelial cells, especially those of capillaries and venules. These results support the hypothesis that angiotensin I and bradykinin are metabolized by enzymes on the luminal surface of pulmonary endothelial cells."} {"id": "PMID:168878", "title": "Hepatic clearance of adenosine 3:5-cyclic monophosphate from plasma in the rat.", "content": "Rats were given intravenous injections of cyclic [3H]AMP and the disappearance of radioactivity from plasma and its appearance in bile were followed. Livers were removed and the cyclic [3H]AMP content was measured. The binding of radioactivity to soluble proteins was measured after preparations of a cytoplasmic fraction. Experiments in vitro to determine the ability of hepatic cytoplasmic proteins to bind cyclic [3H]AMP were also carried out. A role for cytoplasmic proteins in the clearance of cyclic AMP from plasma is discounted.", "contents": "Hepatic clearance of adenosine 3:5-cyclic monophosphate from plasma in the rat. Rats were given intravenous injections of cyclic [3H]AMP and the disappearance of radioactivity from plasma and its appearance in bile were followed. Livers were removed and the cyclic [3H]AMP content was measured. The binding of radioactivity to soluble proteins was measured after preparations of a cytoplasmic fraction. Experiments in vitro to determine the ability of hepatic cytoplasmic proteins to bind cyclic [3H]AMP were also carried out. A role for cytoplasmic proteins in the clearance of cyclic AMP from plasma is discounted."} {"id": "PMID:168879", "title": "Kinetic studies on the reaction between cytochrome c oxidase and ferrocytochrome c.", "content": "In stopped-flow experiments in which oxidized cytochrome c oxidase was mixed with ferrocytochrome c in the presence of a range of oxygen concentrations and in the absence and presence of cyanide, a fast phase, reflecting a rapid approach to an equilibrium, was observed. Within this phase, one or two molecules of ferrocytochrome were oxidized per haem group of cytochrome a, depending on the concentration of ferrocytochrome c used. The reasons for this are discussed in terms of a mechanism in which all electrons enter through cytochrome a, which, in turn, is in rapid equilibrium with a second site, identified with 'visible' copper (830 nm-absorbing) Cud (Beinert et al., 1971). The value of the bimolecular rate constant for the reaction between cytochromes c2+ and a3+ was between 10(6) and 10(7) M(-1)-S(-1); some variability from preparation to preparation was observed. At high ferrocytochrome c concentrations, the initial reaction of cytochrome c2+ with cytochrome a3+ could be isolated from the reaction involving the 'visible' copper and the stoicheiometry was found to approach one molecule of cytochrome c2+ oxidized for each molecule of cytochrome a3+ reduced. At low ferrocytochrome c concentrations, however, both sites (i.e. cytochrome a and Cud) were reduced simultaneously and the stoicheiometry of the initial reaction was closer to two molecules of cytochrome c2+ oxidized per molecule of cytochrome a reduced. The bleaching of the 830 nm band lagged behind or was simultaneous with the formation of the 605 nm band and does not depend on the cytochrome c concentration, whereas the extinction at the steady-state does. The time-course of the return of the 830 nm-absorbing species is much faster than the bleaching of the 605 nm-absorbing component, and parallels that of the turnover phase of cytochrome c2+ oxidation. Additions of cyanide to the oxidase preparations had no effect on the observed stoicheiometry or kinetics of the reduction of cytochrome a and 'visible' copper, but inhibited electron transfer to the other two sites, cytochrome a3 and the undetectable copper, Cuu.", "contents": "Kinetic studies on the reaction between cytochrome c oxidase and ferrocytochrome c. In stopped-flow experiments in which oxidized cytochrome c oxidase was mixed with ferrocytochrome c in the presence of a range of oxygen concentrations and in the absence and presence of cyanide, a fast phase, reflecting a rapid approach to an equilibrium, was observed. Within this phase, one or two molecules of ferrocytochrome were oxidized per haem group of cytochrome a, depending on the concentration of ferrocytochrome c used. The reasons for this are discussed in terms of a mechanism in which all electrons enter through cytochrome a, which, in turn, is in rapid equilibrium with a second site, identified with 'visible' copper (830 nm-absorbing) Cud (Beinert et al., 1971). The value of the bimolecular rate constant for the reaction between cytochromes c2+ and a3+ was between 10(6) and 10(7) M(-1)-S(-1); some variability from preparation to preparation was observed. At high ferrocytochrome c concentrations, the initial reaction of cytochrome c2+ with cytochrome a3+ could be isolated from the reaction involving the 'visible' copper and the stoicheiometry was found to approach one molecule of cytochrome c2+ oxidized for each molecule of cytochrome a3+ reduced. At low ferrocytochrome c concentrations, however, both sites (i.e. cytochrome a and Cud) were reduced simultaneously and the stoicheiometry of the initial reaction was closer to two molecules of cytochrome c2+ oxidized per molecule of cytochrome a reduced. The bleaching of the 830 nm band lagged behind or was simultaneous with the formation of the 605 nm band and does not depend on the cytochrome c concentration, whereas the extinction at the steady-state does. The time-course of the return of the 830 nm-absorbing species is much faster than the bleaching of the 605 nm-absorbing component, and parallels that of the turnover phase of cytochrome c2+ oxidation. Additions of cyanide to the oxidase preparations had no effect on the observed stoicheiometry or kinetics of the reduction of cytochrome a and 'visible' copper, but inhibited electron transfer to the other two sites, cytochrome a3 and the undetectable copper, Cuu."} {"id": "PMID:168880", "title": "Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen-storage disease. A study of phosphorylase kinase deficiency.", "content": "1. The properties of phosphorylase a, phosphorylase b, phosphorylase kinase and phosphorylase phosphatase present in a human haemolysate were investigated. The two forms of phosphorylase have the same affinity for glucose 1-phosphate but greatly differ in Vmax. Phosphorylase b is only partially stimulated by AMP, since, in the presence of the nucleotide, it is about tenfold less active than phosphorylase a. In a fresh human haemolysate phosphorylase is mostly in the b form; it is converted into phosphorylase a by incubation at 20degreesC, and this reaction is stimulated by glycogen and cyclic AMP. Once activated, the enzyme can be inactivated after filtration of the haemolysate on Sephadex G-25. This inactivation is stimulated by caffeine and glucose and inhibited by AMP and fluoride. The phosphorylase kinase present in the haemolysate can also be measured by the rate of activation of added muscle phosphorylase b, on addition of ATP and Mg2+. 2. The activity of phosphorylase kinase was measured in haemolysates obtained from a series of patients who had been classified as suffering from type VI glycogenosis. In nine patients, all boys, an almost complete deficiency of phosphorylase kinase was observed in the haemolysate and, when it could be assayed, in the liver. A residual activity, about 20% of normal, was found in the leucocyte fraction, whereas the enzyme activity was normal in the muscle. These patients suffer from the sex-linked phosphorylase kinase deficiency previously described by others. Two pairs of siblings, each time brother and sister, displayed a partial deficiency of phosphorylase kinase in the haemolysate and leucocytes and an almost complete deficiency in the liver. This is considered as being the autosomal form of phosphorylase kinase deficiency. Other patients were characterized by a low activity of total (a+b) phosphorylase and a normal or high activity of phosphorylase kinase in their haemolysate.", "contents": "Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen-storage disease. A study of phosphorylase kinase deficiency. 1. The properties of phosphorylase a, phosphorylase b, phosphorylase kinase and phosphorylase phosphatase present in a human haemolysate were investigated. The two forms of phosphorylase have the same affinity for glucose 1-phosphate but greatly differ in Vmax. Phosphorylase b is only partially stimulated by AMP, since, in the presence of the nucleotide, it is about tenfold less active than phosphorylase a. In a fresh human haemolysate phosphorylase is mostly in the b form; it is converted into phosphorylase a by incubation at 20degreesC, and this reaction is stimulated by glycogen and cyclic AMP. Once activated, the enzyme can be inactivated after filtration of the haemolysate on Sephadex G-25. This inactivation is stimulated by caffeine and glucose and inhibited by AMP and fluoride. The phosphorylase kinase present in the haemolysate can also be measured by the rate of activation of added muscle phosphorylase b, on addition of ATP and Mg2+. 2. The activity of phosphorylase kinase was measured in haemolysates obtained from a series of patients who had been classified as suffering from type VI glycogenosis. In nine patients, all boys, an almost complete deficiency of phosphorylase kinase was observed in the haemolysate and, when it could be assayed, in the liver. A residual activity, about 20% of normal, was found in the leucocyte fraction, whereas the enzyme activity was normal in the muscle. These patients suffer from the sex-linked phosphorylase kinase deficiency previously described by others. Two pairs of siblings, each time brother and sister, displayed a partial deficiency of phosphorylase kinase in the haemolysate and leucocytes and an almost complete deficiency in the liver. This is considered as being the autosomal form of phosphorylase kinase deficiency. Other patients were characterized by a low activity of total (a+b) phosphorylase and a normal or high activity of phosphorylase kinase in their haemolysate."} {"id": "PMID:168881", "title": "Isolation and protein composition of membranes of neurosecretory vesicles and plasma membranes from the neural lobe of the bovine pituitary gland.", "content": "1. Homogenates of neural lobes of bovine pituitary glands were fractionated by differential ultracentrifugation. 2. Neurosecretory vesicles were isolated by sucrose-gradient ultracentrifugation and membranes were obtained after hypo-osmotic lysis of the particles. 3. A method is described for the isolation of a preparation of purified neuronal plasma membranes by using a fraction enriched in nerve endings as a starting material. 4. The purity of the subcellular fractions was estimated by enzyme assays and by examination with the electron microscope. 5. On the basis of the results it was estimated that neuronal plasma membranes constitute more than 30% of the protein of the nerve endings and neurosecretory vesicles more than 45% of the total amount of protein in the homogenate. 6. The proteins of membranes of neurosecretory vesicles and of plasma membranes were solubilized by means of sodium dodecyl sulphate. Polyacrylamide-gel electrophoresis of such preparations showed that both membranes contained a large number of proteins, including three glycoproteins.", "contents": "Isolation and protein composition of membranes of neurosecretory vesicles and plasma membranes from the neural lobe of the bovine pituitary gland. 1. Homogenates of neural lobes of bovine pituitary glands were fractionated by differential ultracentrifugation. 2. Neurosecretory vesicles were isolated by sucrose-gradient ultracentrifugation and membranes were obtained after hypo-osmotic lysis of the particles. 3. A method is described for the isolation of a preparation of purified neuronal plasma membranes by using a fraction enriched in nerve endings as a starting material. 4. The purity of the subcellular fractions was estimated by enzyme assays and by examination with the electron microscope. 5. On the basis of the results it was estimated that neuronal plasma membranes constitute more than 30% of the protein of the nerve endings and neurosecretory vesicles more than 45% of the total amount of protein in the homogenate. 6. The proteins of membranes of neurosecretory vesicles and of plasma membranes were solubilized by means of sodium dodecyl sulphate. Polyacrylamide-gel electrophoresis of such preparations showed that both membranes contained a large number of proteins, including three glycoproteins."} {"id": "PMID:168882", "title": "Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase.", "content": "1. The mechanism by which insulin activates pyruvate dehydrogenase in rat epididymal adipose tissue was further investigated. 2. When crude extracts, prepared from tissue segments previously exposed to insulin (2m-i.u/ml) for 2min, were supplemented with Mg-2+, Ca-2+, glucose and hexokinase and incubated at 30 degrees C, they displayed an enhanced rate of increase in pyruvate dehydrogenase activity compared with control extracts. 3. When similar extracts were instead supplemented with fluoride, ADP, creatine phosphate and creatine kinase, the rate of decrease in pyruvate dehydrogenase activity observed during incubation at 30 degrees C was unaffected by insulin treatment. 4. It is suggested that insulin increases the fraction of pyruvate dehydrogenase present in the tissue in the active dephospho form by increasing the activity of pyruvate dehydrogenase phosphate phosphatase.", "contents": "Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase. 1. The mechanism by which insulin activates pyruvate dehydrogenase in rat epididymal adipose tissue was further investigated. 2. When crude extracts, prepared from tissue segments previously exposed to insulin (2m-i.u/ml) for 2min, were supplemented with Mg-2+, Ca-2+, glucose and hexokinase and incubated at 30 degrees C, they displayed an enhanced rate of increase in pyruvate dehydrogenase activity compared with control extracts. 3. When similar extracts were instead supplemented with fluoride, ADP, creatine phosphate and creatine kinase, the rate of decrease in pyruvate dehydrogenase activity observed during incubation at 30 degrees C was unaffected by insulin treatment. 4. It is suggested that insulin increases the fraction of pyruvate dehydrogenase present in the tissue in the active dephospho form by increasing the activity of pyruvate dehydrogenase phosphate phosphatase."} {"id": "PMID:168883", "title": "The mannophosphoinositides of Corynebacterium aquaticum.", "content": "Besides the monomannophosphoinositide previously reported in Corynebacterium aquaticum small amounts of other, apparently more glycosylated, mannophosphoinositides have been identified in stationary phase cells. Moreover, by labelling cells with [32P]Pi, phosphatidylinositol was found, comprising about 1.5% of the stationary-phase phospholipids. 2. Pulse-chase experiments performed on cells in the late exponential phase of growth further suggested the sequence phosphatidylinositol leads to monomannophosphoinositide as the first step in the biosynthesis of the mannophosphoinositides. 3. Di-and tri-mannophosphoinositides are apparently the main mannophosphoinositides present during exponential growth. Monomannophosphoinositide predominates only in late stationary phase; in the earlier stationary phase, phosphatidylinositol comprises 50% of the phosphoinositide lipid, and tetramannophosphoinositide constitutes much of the remainder. 4. The metabolism and functions of the mannophosphoinositides are discussed, particularly in relation to changes in their composition throughout the growth cycle.", "contents": "The mannophosphoinositides of Corynebacterium aquaticum. Besides the monomannophosphoinositide previously reported in Corynebacterium aquaticum small amounts of other, apparently more glycosylated, mannophosphoinositides have been identified in stationary phase cells. Moreover, by labelling cells with [32P]Pi, phosphatidylinositol was found, comprising about 1.5% of the stationary-phase phospholipids. 2. Pulse-chase experiments performed on cells in the late exponential phase of growth further suggested the sequence phosphatidylinositol leads to monomannophosphoinositide as the first step in the biosynthesis of the mannophosphoinositides. 3. Di-and tri-mannophosphoinositides are apparently the main mannophosphoinositides present during exponential growth. Monomannophosphoinositide predominates only in late stationary phase; in the earlier stationary phase, phosphatidylinositol comprises 50% of the phosphoinositide lipid, and tetramannophosphoinositide constitutes much of the remainder. 4. The metabolism and functions of the mannophosphoinositides are discussed, particularly in relation to changes in their composition throughout the growth cycle."} {"id": "PMID:168884", "title": "Inactivation of glucose 6-phosphate dehydrogenase during germination and outgrowth of Bacillus cereus T endospores.", "content": "The specific activity and total activity of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) under conditions of complete cell breakage fall 10-20-fold during a 3h period of spore germination and outgrowth. The spores must germinate (lose refractility), but do not have to undergo outgrowth, for the loss of activity to occur. Glucose 6-phosphate dehydrogenase activity from cells as any stage of development is completely stable in extracts at 4 degrees C or 30 degrees C. All of the enzyme activity is found in a soluble (50000g supernatant) fraction and remains completely soluble throughout development. Soluble protein and total cellular protein remain constant for about 2h. Proteinases could not be detected or protein turnover demonstrated during the morphogenetic process. Phenylmethanesuophony fluoride and o-phenanthroline, inhibitors of proteolytic enzymes, do not prevent glucose 6-phosphate dehydrogenase inactivation when added to whole cells. Mixing experiments show no inhibitor of glucose 6-phosphate dehydrogenase to be present in late-stage cells. The enzyme is not excreted into the culture medium. Chloramphenicol and rifampicine immediately stop protein synthesis and development but not the inactivation of glucose 6-phosphate dehydrogenase. NaN3, 2,4-dinitrophenol or anaerobiosis immediately stop development and prevent the loss of enzyme activity. A requirement for metabolic energy is therefore probable. Extracts of spores pre-labelled with L[14C]leucine were made at various stages of morphogenesis and subjected to polyacrylamide-gel electrophoresis. Glucose 6-phosphate dehydrogenase, which was identified by a specific stain, did not lose 14C label, and therefore may not be degraded during the inactivation process.", "contents": "Inactivation of glucose 6-phosphate dehydrogenase during germination and outgrowth of Bacillus cereus T endospores. The specific activity and total activity of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) under conditions of complete cell breakage fall 10-20-fold during a 3h period of spore germination and outgrowth. The spores must germinate (lose refractility), but do not have to undergo outgrowth, for the loss of activity to occur. Glucose 6-phosphate dehydrogenase activity from cells as any stage of development is completely stable in extracts at 4 degrees C or 30 degrees C. All of the enzyme activity is found in a soluble (50000g supernatant) fraction and remains completely soluble throughout development. Soluble protein and total cellular protein remain constant for about 2h. Proteinases could not be detected or protein turnover demonstrated during the morphogenetic process. Phenylmethanesuophony fluoride and o-phenanthroline, inhibitors of proteolytic enzymes, do not prevent glucose 6-phosphate dehydrogenase inactivation when added to whole cells. Mixing experiments show no inhibitor of glucose 6-phosphate dehydrogenase to be present in late-stage cells. The enzyme is not excreted into the culture medium. Chloramphenicol and rifampicine immediately stop protein synthesis and development but not the inactivation of glucose 6-phosphate dehydrogenase. NaN3, 2,4-dinitrophenol or anaerobiosis immediately stop development and prevent the loss of enzyme activity. A requirement for metabolic energy is therefore probable. Extracts of spores pre-labelled with L[14C]leucine were made at various stages of morphogenesis and subjected to polyacrylamide-gel electrophoresis. Glucose 6-phosphate dehydrogenase, which was identified by a specific stain, did not lose 14C label, and therefore may not be degraded during the inactivation process."} {"id": "PMID:168885", "title": "Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat.", "content": "Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P-450, and the activities of NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were unchanged. Propan-2-ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P-450 was unchanged whereas NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were both increased by 38%. Methanol, ethanol and propan-2-ol administration resulted in a decreased type I spectral change but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan-2-ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding to the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P-450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P-450 reduction.", "contents": "Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat. Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P-450, and the activities of NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were unchanged. Propan-2-ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P-450 was unchanged whereas NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were both increased by 38%. Methanol, ethanol and propan-2-ol administration resulted in a decreased type I spectral change but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan-2-ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding to the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P-450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P-450 reduction."} {"id": "PMID:168886", "title": "Inhibition of glucose 6-phosphatase by pure and impure C-type phospholipases. Reactivation by phospholipid dispersions and protection by serum albumin.", "content": "1. Pure or impure C-type phospholipases hydrolysed rat liver microsomal phosphatides in situ at 5 degrees or 37 degrees C. At 5 degrees C mean hydrolysis of total phospholipids was 90% by Bacillus cereus and 75% by Clostridium perfringens (Clostridium welchii) C-type phospholipases. 2. Four degrees of inhibition of glucose 6-phosphatase (D-glucose 6-phosphate phosphohydrolase; EC 3.1.3.9) resulted. (a) At 37 degrees C inhibition was virtually complete and apparently irreversible. (b) At 5 degrees C phospholipase C inhibited 50-87% of the activity expressed by intact control microsomal fractions. (c) Bovine serum albumin present during delipidation alleviated most of this inhibition: at 5 degrees C phospholipase C plus bovine serum albumin inhibited by 0-35% (mean 18%):simultaneous stimulation by the destruction of its latency seems to offset glucose 6-phosphatase inhibition, sometimes completely. (d) If latency was first destroyed, phospholipase C plus bovine serum albumin inhibited 30-50% of total glucose 6-phosphatase activity at 5 degrees C. Only this inhibition is likely largely to reflect the lower availability of phospholipids, essential for maximal enzyme activity, as it is virtually completely reversed by added phospholipid dispersions. Co-dispersions of phosphatidylserine plus phosphatidylcholine (1:1, w/w) were especially effective but Triton X-100 was unable effectively to restore activity. 3. Considerable glucose 6-phosphatase activity survived 240min of treatment with phospholipase C at 5 degrees C, but in the absence of substrate or at physiological glucose 6-phosphate concentrations the delipidated enzyme was completely inactivated within 10min at 37 degrees C. However, 80mM-glucose 6-phosphate stabilized it and phospholipid dispersions substantially restored thermal stability. 4. It is concluded that glucose 6-phosphatase is at least partly phospholipid-dependent, and complete dependence is not excluded. For reasons discussed it is impossible yet to be certain which phospholipid class(es) the enzyme requires for activity.", "contents": "Inhibition of glucose 6-phosphatase by pure and impure C-type phospholipases. Reactivation by phospholipid dispersions and protection by serum albumin. 1. Pure or impure C-type phospholipases hydrolysed rat liver microsomal phosphatides in situ at 5 degrees or 37 degrees C. At 5 degrees C mean hydrolysis of total phospholipids was 90% by Bacillus cereus and 75% by Clostridium perfringens (Clostridium welchii) C-type phospholipases. 2. Four degrees of inhibition of glucose 6-phosphatase (D-glucose 6-phosphate phosphohydrolase; EC 3.1.3.9) resulted. (a) At 37 degrees C inhibition was virtually complete and apparently irreversible. (b) At 5 degrees C phospholipase C inhibited 50-87% of the activity expressed by intact control microsomal fractions. (c) Bovine serum albumin present during delipidation alleviated most of this inhibition: at 5 degrees C phospholipase C plus bovine serum albumin inhibited by 0-35% (mean 18%):simultaneous stimulation by the destruction of its latency seems to offset glucose 6-phosphatase inhibition, sometimes completely. (d) If latency was first destroyed, phospholipase C plus bovine serum albumin inhibited 30-50% of total glucose 6-phosphatase activity at 5 degrees C. Only this inhibition is likely largely to reflect the lower availability of phospholipids, essential for maximal enzyme activity, as it is virtually completely reversed by added phospholipid dispersions. Co-dispersions of phosphatidylserine plus phosphatidylcholine (1:1, w/w) were especially effective but Triton X-100 was unable effectively to restore activity. 3. Considerable glucose 6-phosphatase activity survived 240min of treatment with phospholipase C at 5 degrees C, but in the absence of substrate or at physiological glucose 6-phosphate concentrations the delipidated enzyme was completely inactivated within 10min at 37 degrees C. However, 80mM-glucose 6-phosphate stabilized it and phospholipid dispersions substantially restored thermal stability. 4. It is concluded that glucose 6-phosphatase is at least partly phospholipid-dependent, and complete dependence is not excluded. For reasons discussed it is impossible yet to be certain which phospholipid class(es) the enzyme requires for activity."} {"id": "PMID:168887", "title": "Synthesis and sideedness of membrane-bound respiratory nitrate reductase (EC1.7.99.4) in Escherichia coli lacking cytochromes.", "content": "The synthesis of nitrate reductase and its incorporation into the cytoplasmic membrane of Escherichia coli strain A1004a (5-aminolaevulinic acid auxotroph) does not require synthesis of cytochrome b. The synthesis of the apoprotein(s) of the cytochrome b of the respiratory pathway from NADH to nitrate appears to be inhibited by the absence of haem. No member of the respiratory pathway from NADH to oxygen is capable of reducing nitrate reductase directly. The site on nitrate reductase that oxidizes FMNH2 is located on the cytoplasmic aspect of the cytoplasmic membrane.", "contents": "Synthesis and sideedness of membrane-bound respiratory nitrate reductase (EC1.7.99.4) in Escherichia coli lacking cytochromes. The synthesis of nitrate reductase and its incorporation into the cytoplasmic membrane of Escherichia coli strain A1004a (5-aminolaevulinic acid auxotroph) does not require synthesis of cytochrome b. The synthesis of the apoprotein(s) of the cytochrome b of the respiratory pathway from NADH to nitrate appears to be inhibited by the absence of haem. No member of the respiratory pathway from NADH to oxygen is capable of reducing nitrate reductase directly. The site on nitrate reductase that oxidizes FMNH2 is located on the cytoplasmic aspect of the cytoplasmic membrane."} {"id": "PMID:168888", "title": "Specificity of the effect of dietary cholesterol on rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme a reductase activity.", "content": "Dietary cholesterol lowers the activity of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase without affecting various other liver microsomal enzymes. This is consistent with a specific regulatory mechanism and distinguishes the action of cholesterol on 3-hydroxy-3-methylglutaryl-CoA reductase from that of at least one other stimulus known to affect this enzyme.", "contents": "Specificity of the effect of dietary cholesterol on rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme a reductase activity. Dietary cholesterol lowers the activity of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase without affecting various other liver microsomal enzymes. This is consistent with a specific regulatory mechanism and distinguishes the action of cholesterol on 3-hydroxy-3-methylglutaryl-CoA reductase from that of at least one other stimulus known to affect this enzyme."} {"id": "PMID:168907", "title": "[Mechanisms of platelet aggregation inhibition caused by sulfonylurea compounds. 4. Discussion, summary, and literature].", "content": "6.1. It is known from the literature that in diabetes mellitus there is an increased tendency for the thrombocytes to aggregate. This fact represents a risk of thrombosis supplementary to the vascular wall lesions which develop in the course of this disease. An inhibition of platelet aggregation such as has recently been obse3rved in vitro under the influence of beta-cytotropic sulphonylureas (tolbutamide, glicalazide), must therefore be regarded as an additional, desired quality of action of these agents. 6.2. In an attempt to throw more light on this subject studies were conducted to discover whether an inhibition of platelet aggregation can be regarded as a basic property of all beta-cytotropic antidiabetic agents and whether dissociation exists between this property and the hypoglycemic effect. The possible existence of evidence for identical or similar sites of action of sulphonylureas on the control system of the thrombocytes, beta-cells and the liver was also investigated, the main point of interest being whether sulphonylurea derivatives exert their effects via the adenylate cyclase -cAMP-system. The thrombocytes were also used to discover whteher ss-cytotropic antidiabetic agents, such as non-steroidal antiphlogistic compounds, inhibit the synthesis of aggregation-promoting prostaglandins (PGE2). 6.3. The influence on adenosine diphosphate (ADP)-induced thrombocyte aggregation has been dtudied in vitro with platelet rich rat plasma (PRP) using a turbidimetric method. Preliminary studies have also been conducted with PRP obtained after previous treatment of the donor animals...", "contents": "[Mechanisms of platelet aggregation inhibition caused by sulfonylurea compounds. 4. Discussion, summary, and literature]. 6.1. It is known from the literature that in diabetes mellitus there is an increased tendency for the thrombocytes to aggregate. This fact represents a risk of thrombosis supplementary to the vascular wall lesions which develop in the course of this disease. An inhibition of platelet aggregation such as has recently been obse3rved in vitro under the influence of beta-cytotropic sulphonylureas (tolbutamide, glicalazide), must therefore be regarded as an additional, desired quality of action of these agents. 6.2. In an attempt to throw more light on this subject studies were conducted to discover whether an inhibition of platelet aggregation can be regarded as a basic property of all beta-cytotropic antidiabetic agents and whether dissociation exists between this property and the hypoglycemic effect. The possible existence of evidence for identical or similar sites of action of sulphonylureas on the control system of the thrombocytes, beta-cells and the liver was also investigated, the main point of interest being whether sulphonylurea derivatives exert their effects via the adenylate cyclase -cAMP-system. The thrombocytes were also used to discover whteher ss-cytotropic antidiabetic agents, such as non-steroidal antiphlogistic compounds, inhibit the synthesis of aggregation-promoting prostaglandins (PGE2). 6.3. The influence on adenosine diphosphate (ADP)-induced thrombocyte aggregation has been dtudied in vitro with platelet rich rat plasma (PRP) using a turbidimetric method. Preliminary studies have also been conducted with PRP obtained after previous treatment of the donor animals..."} {"id": "PMID:168905", "title": "Retardation of colony growth of in vitro bone marrow culture using sera from patients with Felty's syndrome, disseminated lupus erythematosus (SLE), rheumatoid arthritis, and other disease states.", "content": "Whole sera and serum fractions from 24 patients with Felty's syndrome, 42 patients with systemic lupus erythematosus (SLE), and 48 patients with rheumatoid arthritis (RA), as well as 30 patients with miscellaneous acute and chronic disease states, were studied for their effect on numbers of mouse bone marrow colonies grown on soft agar in the presence of human colony stimulating factor. Significant early retardation of mouse bone marrow colony counts was recorded in 87.5 percent of Felty's sera, 43 percent of SLE sera, and 12.5 percent of sera from patients with uncomplicated RA. Forty percent of 30 other control patients with acute or chronic inflammatory diseases also showed this activity. No diminution was noted with any of 40 normal control sera. Degree of marrow colony retardation could be directly correlated to amounts of test serum added. No single serum fraction isolated by ion exchange chromatography, gel filtration, or electrophoresis was identified as solely responsible for marrow growth retardation; however lipoprotein fractions including chylomicrons, LDL and HDL showed inhibiting activity in various sera.", "contents": "Retardation of colony growth of in vitro bone marrow culture using sera from patients with Felty's syndrome, disseminated lupus erythematosus (SLE), rheumatoid arthritis, and other disease states. Whole sera and serum fractions from 24 patients with Felty's syndrome, 42 patients with systemic lupus erythematosus (SLE), and 48 patients with rheumatoid arthritis (RA), as well as 30 patients with miscellaneous acute and chronic disease states, were studied for their effect on numbers of mouse bone marrow colonies grown on soft agar in the presence of human colony stimulating factor. Significant early retardation of mouse bone marrow colony counts was recorded in 87.5 percent of Felty's sera, 43 percent of SLE sera, and 12.5 percent of sera from patients with uncomplicated RA. Forty percent of 30 other control patients with acute or chronic inflammatory diseases also showed this activity. No diminution was noted with any of 40 normal control sera. Degree of marrow colony retardation could be directly correlated to amounts of test serum added. No single serum fraction isolated by ion exchange chromatography, gel filtration, or electrophoresis was identified as solely responsible for marrow growth retardation; however lipoprotein fractions including chylomicrons, LDL and HDL showed inhibiting activity in various sera."} {"id": "PMID:168908", "title": "Beta-phenylethylamine and locomotor activity in mice. Interaction with catecholaminergic neurones and receptors.", "content": "Beta-Phenylethylamine on injection into mice produced both an early and late phase of increased locomotor activity. The early phase produced by 50 mg phenylethylamine/kg was inhibited by pretreatment with phenoxybenzamine, phentolamine, alpha-methyl-tyrosine, diethyldithiocarbamate, pimozide and haloperidol, but not by propranolol, protriptyline and reserpine. The late phase produced by 100 mg phenylethylamine/kg was blocked only by pimozide and haloperidol, both of these in doses at least ten times higher than those required to block the early phase. From these results it was concluded that the increased early phase of locomotor activity was due to the release of dopamine and noradrenaline synthetic pathway, but not intact reserpine sensitive amine stores. In contrast the late phase of locomotor activity was independent of catecholamine stores and appeared to be produced by a direct action by either phenylethylamine or metabolites on dopamine receptors.", "contents": "Beta-phenylethylamine and locomotor activity in mice. Interaction with catecholaminergic neurones and receptors. Beta-Phenylethylamine on injection into mice produced both an early and late phase of increased locomotor activity. The early phase produced by 50 mg phenylethylamine/kg was inhibited by pretreatment with phenoxybenzamine, phentolamine, alpha-methyl-tyrosine, diethyldithiocarbamate, pimozide and haloperidol, but not by propranolol, protriptyline and reserpine. The late phase produced by 100 mg phenylethylamine/kg was blocked only by pimozide and haloperidol, both of these in doses at least ten times higher than those required to block the early phase. From these results it was concluded that the increased early phase of locomotor activity was due to the release of dopamine and noradrenaline synthetic pathway, but not intact reserpine sensitive amine stores. In contrast the late phase of locomotor activity was independent of catecholamine stores and appeared to be produced by a direct action by either phenylethylamine or metabolites on dopamine receptors."} {"id": "PMID:168906", "title": "Antibody levels to parainfluenza, rubella, measles, and influenza A virus in children with polymyositis.", "content": "The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenxa A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenxa 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered.", "contents": "Antibody levels to parainfluenza, rubella, measles, and influenza A virus in children with polymyositis. The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenxa A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenxa 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered."} {"id": "PMID:168912", "title": "Failure to detect antibody against Gross virus in tetraparental AKR reversible CBA mouse chimaeras.", "content": "In spite of early acquisition upon the germ line, tolerance to the Gross (gs) virus is short-lived in the AKR. From about the age of 3 months anti-gs antibodies occur and these complex with the corresponding viral antigens. Such complexes are best seen in the glomeruli by means of immunofluorescence. In marked contrast to the AKR, renal complexes were minimal in a group of AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. This was particularly surprising since large numbers of type C murine leukaemia virus-like particles were identified in the chimaeras and the tissues were found to be saturated with gs antigen. The lack of renal antigen-antibody complexes was the first suggestion that anti-gs antibody might not be present in the chimaeras and renal elution studies here support this assumption. In contrast to the AKR where \"split \" renal eluates have been shown to have anti-gs activity, no activity was demonstrated in eluates from any of the chimaras. Tolerance to the oncogenic Gross virus in the chimaeras has to be attributed to the CBA parental strain component and since this component is also held responsible for the tumour resistance of these chimaeras, both phenomena could well be related. In this context it would appear that in the absence of masking by antibody viral antigenic complexes, tumour specific sites can be recognized in the chimaeras and unlike the AKR \"normal\" tumour immunity can be effected. This hypothesis is currently bei-ng tested.", "contents": "Failure to detect antibody against Gross virus in tetraparental AKR reversible CBA mouse chimaeras. In spite of early acquisition upon the germ line, tolerance to the Gross (gs) virus is short-lived in the AKR. From about the age of 3 months anti-gs antibodies occur and these complex with the corresponding viral antigens. Such complexes are best seen in the glomeruli by means of immunofluorescence. In marked contrast to the AKR, renal complexes were minimal in a group of AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. This was particularly surprising since large numbers of type C murine leukaemia virus-like particles were identified in the chimaeras and the tissues were found to be saturated with gs antigen. The lack of renal antigen-antibody complexes was the first suggestion that anti-gs antibody might not be present in the chimaeras and renal elution studies here support this assumption. In contrast to the AKR where \"split \" renal eluates have been shown to have anti-gs activity, no activity was demonstrated in eluates from any of the chimaras. Tolerance to the oncogenic Gross virus in the chimaeras has to be attributed to the CBA parental strain component and since this component is also held responsible for the tumour resistance of these chimaeras, both phenomena could well be related. In this context it would appear that in the absence of masking by antibody viral antigenic complexes, tumour specific sites can be recognized in the chimaeras and unlike the AKR \"normal\" tumour immunity can be effected. This hypothesis is currently bei-ng tested."} {"id": "PMID:168909", "title": "Changes in rabbit lipoprotein properties by dietary cholesterol, and saturated and polyunsaturated fats.", "content": "Plasma lipids and chemical, electrophoretic and electron microscopic properties of VLDL, LDL and HDL are examined in rabbits fed a control diet (group I) or diets containing 1% cholesterol (group II), 1% cholesterol + 5% coconut oil (group III) or 1% cholesterol + 5% corn oil (group IV). The diets II, III and IV resulted in hypercholesterolemia, hypertriglyceridemia and hyperphospholipidemia. The lipid-protein composition of VLDL, LDL and HDL is changed by these diets. There is marked increase in the total cholesterol content of all lipoprotein fractions of the high fat dietary groups II, III and IV. The electrophoretic mobilities of the VLDL and LDL II and III are reduced while the respective mobilities in the corn oil group IV are nearly \"normal\". In contrast to the control LDL fraction I which is not precipitated by heparin, the LDL fractions of the dietary groups II, III and IV are readily precipitated. The apoprotein pattern of the lipoproteins in polyacrylamide gel differs distinctly between the dietary groups, most bands appearing in group IV. An abnormal stacking of lipoprotein particles in electron micrographs of VLDL, LDL and HDL of groups II and III can be observed. In contrast, these lipoprotein fractions of rabbits of the corn oil group IV have morphological properties that are similar to those of the lipoproteins of the control group. It is suggested that these findings are related to the marked reduction of atherosclerosis in rabbits fed a diet with polyunsaturated fat as compared with rabbits on cholesterol and cholesterol-coconut oil diets.", "contents": "Changes in rabbit lipoprotein properties by dietary cholesterol, and saturated and polyunsaturated fats. Plasma lipids and chemical, electrophoretic and electron microscopic properties of VLDL, LDL and HDL are examined in rabbits fed a control diet (group I) or diets containing 1% cholesterol (group II), 1% cholesterol + 5% coconut oil (group III) or 1% cholesterol + 5% corn oil (group IV). The diets II, III and IV resulted in hypercholesterolemia, hypertriglyceridemia and hyperphospholipidemia. The lipid-protein composition of VLDL, LDL and HDL is changed by these diets. There is marked increase in the total cholesterol content of all lipoprotein fractions of the high fat dietary groups II, III and IV. The electrophoretic mobilities of the VLDL and LDL II and III are reduced while the respective mobilities in the corn oil group IV are nearly \"normal\". In contrast to the control LDL fraction I which is not precipitated by heparin, the LDL fractions of the dietary groups II, III and IV are readily precipitated. The apoprotein pattern of the lipoproteins in polyacrylamide gel differs distinctly between the dietary groups, most bands appearing in group IV. An abnormal stacking of lipoprotein particles in electron micrographs of VLDL, LDL and HDL of groups II and III can be observed. In contrast, these lipoprotein fractions of rabbits of the corn oil group IV have morphological properties that are similar to those of the lipoproteins of the control group. It is suggested that these findings are related to the marked reduction of atherosclerosis in rabbits fed a diet with polyunsaturated fat as compared with rabbits on cholesterol and cholesterol-coconut oil diets."} {"id": "PMID:168913", "title": "Transformation of human cells by SV40 virus.", "content": "Fibroblast cultures were prepared from skin biopsies from 29 patients and tested for their susceptibility to transformation by simian virus SV40. Cells with a normal chromosome complement showed a mean transformation frequency of 25/106 cells but for cells from a single patient with Fanconi's anaemia, the value was 152/106 cells. An increased susceptibility to transformation was observed for cells from 6 patients with Down's syndrome 3 patients with trisomy 18, a patient with trisomy 18 for 5% of cells and a patient with trisomy 13. No increased susceptibility to transformation was found for cells with a chromosome complement of XO, XXY, XX/XX + 8, XX + partial 15q or XX + 9p. The susceptiability to transformation was related to susceptibility to SV40 virus infection, as measured by the number of infected cells which contained SV40 virus induced T antigen. This latter test was technically easier to perform and could serve to detect persons of increased susceptiability to transformation, since this may indicate an increased risk of natural malignant disease.", "contents": "Transformation of human cells by SV40 virus. Fibroblast cultures were prepared from skin biopsies from 29 patients and tested for their susceptibility to transformation by simian virus SV40. Cells with a normal chromosome complement showed a mean transformation frequency of 25/106 cells but for cells from a single patient with Fanconi's anaemia, the value was 152/106 cells. An increased susceptibility to transformation was observed for cells from 6 patients with Down's syndrome 3 patients with trisomy 18, a patient with trisomy 18 for 5% of cells and a patient with trisomy 13. No increased susceptibility to transformation was found for cells with a chromosome complement of XO, XXY, XX/XX + 8, XX + partial 15q or XX + 9p. The susceptiability to transformation was related to susceptibility to SV40 virus infection, as measured by the number of infected cells which contained SV40 virus induced T antigen. This latter test was technically easier to perform and could serve to detect persons of increased susceptiability to transformation, since this may indicate an increased risk of natural malignant disease."} {"id": "PMID:168910", "title": "[Aortic development and ageing in the rat aorta -- Comparative histochemical and histoenzymological study (author's transl)].", "content": "A comparative study was made of 36 aortic enzyme activities (E.A.) and 6 macromelecular substances at different stages of ontogenesis in 49 male rats. In the foetal aorta (19th day) the E.Z. were moderate or weak and restricted to a few metabolic pathways: glycolysis, diaphorases, esterolysis of some nucleotides and glucosaminoglycan (GAG) metabolism. During the neonatal period (1st-3rd day), the pre-existing E.A. increased; some aerobic and lipolytic activities became histochemically detectable; longitudinal and radial gradients became established. These changes seemed to provide evidence of increased morphogenic activities and metabolic exchanges. During the prepuberty and puberty period (10-20th day-2nd month) all the E.A., as well as metachromasis and pyroniophilia increased, and new E.A. appeared (GluDH, GPDH, 5/Nase, Ac.Pase-Ca++, Mg++, pH 7.2). These changes appeared to be related to cell proliferation and connective tissue increase during the period of fast aortic growth. The increase of some E.A. (Est/ase, Ch. est, ATPase-Ca++, Mg++, 5/Nase, Alk. Pase) suggested a correlation between enzymatic differentiation and hormonal maturation. During adulthood (6-12th month), the E.A. were stable except for 5/Nase, lysosomal and lipolytic activities which increased. Some E.A. were found to be high (diaphorases, glycolytic and esterolytic enzymes), or moderate (aerobic oxidoreductases, lysosome, lipolysis and GAG-linked E.A.), while others were weak or absent (glycogen pathway E.A.). These observations seemed to correlate with synthetic processes and defence mechanisms. Ageing (17th month) was characterized by an increase of metachromatic GAG and acid lipids and by a decrease of pyroninophillia. Lysosome, glycolysis and phospholipogenesis-linked E.A. increased. In some animals (individual reactivity) kreb's cycle and lypolysis-E.A. decreased.", "contents": "[Aortic development and ageing in the rat aorta -- Comparative histochemical and histoenzymological study (author's transl)]. A comparative study was made of 36 aortic enzyme activities (E.A.) and 6 macromelecular substances at different stages of ontogenesis in 49 male rats. In the foetal aorta (19th day) the E.Z. were moderate or weak and restricted to a few metabolic pathways: glycolysis, diaphorases, esterolysis of some nucleotides and glucosaminoglycan (GAG) metabolism. During the neonatal period (1st-3rd day), the pre-existing E.A. increased; some aerobic and lipolytic activities became histochemically detectable; longitudinal and radial gradients became established. These changes seemed to provide evidence of increased morphogenic activities and metabolic exchanges. During the prepuberty and puberty period (10-20th day-2nd month) all the E.A., as well as metachromasis and pyroniophilia increased, and new E.A. appeared (GluDH, GPDH, 5/Nase, Ac.Pase-Ca++, Mg++, pH 7.2). These changes appeared to be related to cell proliferation and connective tissue increase during the period of fast aortic growth. The increase of some E.A. (Est/ase, Ch. est, ATPase-Ca++, Mg++, 5/Nase, Alk. Pase) suggested a correlation between enzymatic differentiation and hormonal maturation. During adulthood (6-12th month), the E.A. were stable except for 5/Nase, lysosomal and lipolytic activities which increased. Some E.A. were found to be high (diaphorases, glycolytic and esterolytic enzymes), or moderate (aerobic oxidoreductases, lysosome, lipolysis and GAG-linked E.A.), while others were weak or absent (glycogen pathway E.A.). These observations seemed to correlate with synthetic processes and defence mechanisms. Ageing (17th month) was characterized by an increase of metachromatic GAG and acid lipids and by a decrease of pyroninophillia. Lysosome, glycolysis and phospholipogenesis-linked E.A. increased. In some animals (individual reactivity) kreb's cycle and lypolysis-E.A. decreased."} {"id": "PMID:168914", "title": "High affinity oestradiol receptors and the activity of glucose-6-phosphate dehydrogenase and lactose synthetase in mammary carcinomata of postmenopausal women.", "content": "The determination of hormone inducible proteins in endocrine tumours may yield information about the presence of hormone dependent tumour cells. We have estimated the high affinity oestradiol binding capacity in primary mammary carcinomata of 57 postmenopausal patients. Glucose-6-phosphate dehydrogenase and lactose synthetase are known from animal experiments to be hormone inducible. Therefore, in biopsies of sufficient size the activity of glucose-6-phosphate dehydrogenase (47 pateints) and lactose synthetase (23 patients) was also studied. It was found that biopsies with high binding capacity also showed high activities of glucose-6-phosphate dehydrogenase and lactose synthetase A protein (galactosyl transferase). No lactose synthetase B protein (alpha-lactalbumin) has been discovered in the tumours. The present observations may be considered suggestive evidence of a relationship between high oestradiol binding capcity and high activities of the two enzymes on the one hand and hormone dependence of the tumour on the other. However, further clinical studies are required before final conclusions in this respect can be drawn.", "contents": "High affinity oestradiol receptors and the activity of glucose-6-phosphate dehydrogenase and lactose synthetase in mammary carcinomata of postmenopausal women. The determination of hormone inducible proteins in endocrine tumours may yield information about the presence of hormone dependent tumour cells. We have estimated the high affinity oestradiol binding capacity in primary mammary carcinomata of 57 postmenopausal patients. Glucose-6-phosphate dehydrogenase and lactose synthetase are known from animal experiments to be hormone inducible. Therefore, in biopsies of sufficient size the activity of glucose-6-phosphate dehydrogenase (47 pateints) and lactose synthetase (23 patients) was also studied. It was found that biopsies with high binding capacity also showed high activities of glucose-6-phosphate dehydrogenase and lactose synthetase A protein (galactosyl transferase). No lactose synthetase B protein (alpha-lactalbumin) has been discovered in the tumours. The present observations may be considered suggestive evidence of a relationship between high oestradiol binding capcity and high activities of the two enzymes on the one hand and hormone dependence of the tumour on the other. However, further clinical studies are required before final conclusions in this respect can be drawn."} {"id": "PMID:168911", "title": "Familial hyper-HDL-(a)-cholesterolemia.", "content": "In one family the mother, two children and a maternal aunt showed a hypercholesterolemic state characterized by a unusually high percentage of cholesterol in ultracentrifugally-recovered HDL-(a)-LP. An intensely stained a-band was present in all these subjects both in plasma and in ultracentrifugal fraction, with d greater than 1063. Symptoms or signs due to the hypercholesterolemic state were not present. The father was affected by Type IIA hypercholesterolemia. This lipid defect was also present in one of the two children.", "contents": "Familial hyper-HDL-(a)-cholesterolemia. In one family the mother, two children and a maternal aunt showed a hypercholesterolemic state characterized by a unusually high percentage of cholesterol in ultracentrifugally-recovered HDL-(a)-LP. An intensely stained a-band was present in all these subjects both in plasma and in ultracentrifugal fraction, with d greater than 1063. Symptoms or signs due to the hypercholesterolemic state were not present. The father was affected by Type IIA hypercholesterolemia. This lipid defect was also present in one of the two children."} {"id": "PMID:168915", "title": "Activation of murine leukaemia virus under different physiological conditions.", "content": "The leukaemic lesions in intact and ovariectomized mice of strain ICRC, induced with 20-methylcholanthrene (20-MCA) in combination with or without hormones were investigated for the presence of mouse leukaemia virus (MuLV) by (i) bioassays and (ii) electron microscopy. The different experimental groups treated with 20-MCA were (i) intact females, (ii) ovariectomized females, (iii) ovariectomized females with pituitary graft, (iv) ovariectomized females with 10 mug oestradiol/day for 30 days and (v) ovariectomized females with 1 mug oestradiol together with 1 mg progesteron/day for 30 days. It was possible to transmit nearly all these experimentally induced leukaemias to syngeneic mice through acellular extracts, compared with very poor transmissibility of spontaneous leukaemias in the ICRC strain, indicating functional activation of viral agents on combined treatment with carcinogen and hormones. Potency of the acellular leukaemic extract from the mice of group (ii) without the ovarian hormones was much weaker than that from mice of the other experimental groups. The leukaemogenic activity of MuLV was enhanced on serial transmission in syngeneic hosts. Leukaemic lesions of ovariectomized mice treated with 20-MCA and oestradiol were also transmissible to the sucklings of allogeneic mice of strain C3H-MTV, C57-BL and Dba-MTV. The cell-free supernatant medium of the cultures of these leukaemic lesions induced leukaemias on back inoculation into syngeneic mice. Electron microscopic studies of lesions induced with carcinogen and oestradiol consistently showed abundant intracytoplasmic type A particles. Numerous intracytoplasmic type A particles as well as some type B particles were found in the leukaemic tissues of ovariectomized females treated with MCA and oestradiol combined with progesterone. Type C particles, characteristic of MuLV were seen in the leukaemic tissues of all other experimental groups. These findings indicate a significant influence of the physiological condition of the host, particularly the hormonal make up, on expression and activity of specific viral agents.", "contents": "Activation of murine leukaemia virus under different physiological conditions. The leukaemic lesions in intact and ovariectomized mice of strain ICRC, induced with 20-methylcholanthrene (20-MCA) in combination with or without hormones were investigated for the presence of mouse leukaemia virus (MuLV) by (i) bioassays and (ii) electron microscopy. The different experimental groups treated with 20-MCA were (i) intact females, (ii) ovariectomized females, (iii) ovariectomized females with pituitary graft, (iv) ovariectomized females with 10 mug oestradiol/day for 30 days and (v) ovariectomized females with 1 mug oestradiol together with 1 mg progesteron/day for 30 days. It was possible to transmit nearly all these experimentally induced leukaemias to syngeneic mice through acellular extracts, compared with very poor transmissibility of spontaneous leukaemias in the ICRC strain, indicating functional activation of viral agents on combined treatment with carcinogen and hormones. Potency of the acellular leukaemic extract from the mice of group (ii) without the ovarian hormones was much weaker than that from mice of the other experimental groups. The leukaemogenic activity of MuLV was enhanced on serial transmission in syngeneic hosts. Leukaemic lesions of ovariectomized mice treated with 20-MCA and oestradiol were also transmissible to the sucklings of allogeneic mice of strain C3H-MTV, C57-BL and Dba-MTV. The cell-free supernatant medium of the cultures of these leukaemic lesions induced leukaemias on back inoculation into syngeneic mice. Electron microscopic studies of lesions induced with carcinogen and oestradiol consistently showed abundant intracytoplasmic type A particles. Numerous intracytoplasmic type A particles as well as some type B particles were found in the leukaemic tissues of ovariectomized females treated with MCA and oestradiol combined with progesterone. Type C particles, characteristic of MuLV were seen in the leukaemic tissues of all other experimental groups. These findings indicate a significant influence of the physiological condition of the host, particularly the hormonal make up, on expression and activity of specific viral agents."} {"id": "PMID:168916", "title": "Prostaglandins and cyclic AMP in epidermis. Evidence for the independent action of prostaglandins and adrenaline on the adenyl cyclase system of pig and human epidermis, normal and psoriatic.", "content": "Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1,A2 and F2alpha are relatively ineffective. The fact that this stimulation is not inhibited by a beta-blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the beta-receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3X10(-7) M are effective in causing stimulation. This concentration may be within the physilogical range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded.", "contents": "Prostaglandins and cyclic AMP in epidermis. Evidence for the independent action of prostaglandins and adrenaline on the adenyl cyclase system of pig and human epidermis, normal and psoriatic. Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1,A2 and F2alpha are relatively ineffective. The fact that this stimulation is not inhibited by a beta-blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the beta-receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3X10(-7) M are effective in causing stimulation. This concentration may be within the physilogical range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded."} {"id": "PMID:168917", "title": "Adsorption of syndiotactic and isotactic poly(2-vinylpyridine 1-oxide) on quartz surface.", "content": "Poly(2-vinylpyridine 1-oxide) inhibits the cytotoxic effects of quartz in cell cultures but the syndiotactic polymer behaves differently from the isotactic and atactic polymers. In each case approximately 1-0 mg/m2 of the polymer represents the adsorption maximum. No difference has been found between the adsorption isotherms of the stereoisomeric polymers or the stability of the adsorbed layers. The layers are not removed by repeated washing. The observations do not support the theory that the poly(2-vinylpyridine 1-oxide) is active because it coats the quartz surface.", "contents": "Adsorption of syndiotactic and isotactic poly(2-vinylpyridine 1-oxide) on quartz surface. Poly(2-vinylpyridine 1-oxide) inhibits the cytotoxic effects of quartz in cell cultures but the syndiotactic polymer behaves differently from the isotactic and atactic polymers. In each case approximately 1-0 mg/m2 of the polymer represents the adsorption maximum. No difference has been found between the adsorption isotherms of the stereoisomeric polymers or the stability of the adsorbed layers. The layers are not removed by repeated washing. The observations do not support the theory that the poly(2-vinylpyridine 1-oxide) is active because it coats the quartz surface."} {"id": "PMID:168918", "title": "Permeation of a spin-label phosphate into the human erythrocyte.", "content": "The reduction of spin-labels by human erythrocytes can be used to follow their penetration into these cells. The neutral spin-label alcohol Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl) diffuses through the membrane very quickly. The membrane is virtually impermeable to the positively charged spin-label Tempo-choline (N,N-dimethyl-N-(2',2',6',6'-tetramethyl-4'-piperidinyl-1-oxyl)-2-hydroxyethylammonium chloride). The negatively charged spin-label Tempo phosphate (4-phospho-2,2,6,6-tetramethylpiperidinyl-l-oxyl) is reduced at 37 degrees, with a half-time of about 1 hr. The reduction occurs internally following the rate-limiting transport of the label across the erythrocyte membrane. Reduction of this spin-label is greatly diminished by the specific inhibitor of anion transport, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). The rate of transport depends strongly on the transmembrane electrical potential.", "contents": "Permeation of a spin-label phosphate into the human erythrocyte. The reduction of spin-labels by human erythrocytes can be used to follow their penetration into these cells. The neutral spin-label alcohol Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl) diffuses through the membrane very quickly. The membrane is virtually impermeable to the positively charged spin-label Tempo-choline (N,N-dimethyl-N-(2',2',6',6'-tetramethyl-4'-piperidinyl-1-oxyl)-2-hydroxyethylammonium chloride). The negatively charged spin-label Tempo phosphate (4-phospho-2,2,6,6-tetramethylpiperidinyl-l-oxyl) is reduced at 37 degrees, with a half-time of about 1 hr. The reduction occurs internally following the rate-limiting transport of the label across the erythrocyte membrane. Reduction of this spin-label is greatly diminished by the specific inhibitor of anion transport, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). The rate of transport depends strongly on the transmembrane electrical potential."} {"id": "PMID:168919", "title": "Studies on the mechanism of electron transport in the bc1-segment of the respiratory chain in yeast. II. The binding of antimycin to mitochondrial particles and the function of two different binding sites.", "content": "1. In mitochondrial particles antimycin binds to two separate specific sites with dissociation constants KD1 less than 4 - 10(-13) M and KD2 = 3 - 10(-9) M, respectively. 2. The concentrations of the two antimycin binding sites are about equal. The absolute concentration for each binding site is about 100 - 150 pmol per mg of mitochondrial protein. 3. Antimycin bound to the stronger site mainly inhibits NADH-and succinate oxidase. Binding of antimycin to the weaker binding site inhibits the electron flux to exogenously added cytochrome c after blocking cytochrome oxidase by KCN. 4. Under certain conditions cytochrome b and c1 are dispensible components for antimycin-sensitive electron transport. 5. A model of the respiratory chain in yeast is proposed which accounts for the results reported here and previously. (Lang, B., Burger, G., and Bandlow, W. (1974) Biochim. Biophys. Acta 368, 71-85).", "contents": "Studies on the mechanism of electron transport in the bc1-segment of the respiratory chain in yeast. II. The binding of antimycin to mitochondrial particles and the function of two different binding sites. 1. In mitochondrial particles antimycin binds to two separate specific sites with dissociation constants KD1 less than 4 - 10(-13) M and KD2 = 3 - 10(-9) M, respectively. 2. The concentrations of the two antimycin binding sites are about equal. The absolute concentration for each binding site is about 100 - 150 pmol per mg of mitochondrial protein. 3. Antimycin bound to the stronger site mainly inhibits NADH-and succinate oxidase. Binding of antimycin to the weaker binding site inhibits the electron flux to exogenously added cytochrome c after blocking cytochrome oxidase by KCN. 4. Under certain conditions cytochrome b and c1 are dispensible components for antimycin-sensitive electron transport. 5. A model of the respiratory chain in yeast is proposed which accounts for the results reported here and previously. (Lang, B., Burger, G., and Bandlow, W. (1974) Biochim. Biophys. Acta 368, 71-85)."} {"id": "PMID:168920", "title": "Some experiments on the primary electron acceptor in reaction centres from Rhodopseudomonas sphaeroides.", "content": "The bacterial reaction center absorbance change at 450 nm (A-450) assigned to an anionic semiquinone, has been suggested as a candidate for the reduced form of the primary electron acceptor in bacterial photosynthesis. In reaction centers of Rhodopseudomonas sphaeroides we have found kinetic discrepancies between the decay of A-450 and the recovery of photochemical competence. In addition, no proton uptake is measurable on the first turnover, although subsequent ones elicit one proton bound per electron. These results are taken to indicate that the acceptor reaction after a long dark period may be different for the first turnover than for subsequent ones. It is suggested that A-450 is still a likely candidate for the acceptor function but that in reaction centers, additional quinone may act as an adventitious primary acceptor when the \"true\" primary acceptor is reduced. Alternatively, the primary acceptor may act in a \"ping-pong\" fashion with respect to subsequent photoelectrons.", "contents": "Some experiments on the primary electron acceptor in reaction centres from Rhodopseudomonas sphaeroides. The bacterial reaction center absorbance change at 450 nm (A-450) assigned to an anionic semiquinone, has been suggested as a candidate for the reduced form of the primary electron acceptor in bacterial photosynthesis. In reaction centers of Rhodopseudomonas sphaeroides we have found kinetic discrepancies between the decay of A-450 and the recovery of photochemical competence. In addition, no proton uptake is measurable on the first turnover, although subsequent ones elicit one proton bound per electron. These results are taken to indicate that the acceptor reaction after a long dark period may be different for the first turnover than for subsequent ones. It is suggested that A-450 is still a likely candidate for the acceptor function but that in reaction centers, additional quinone may act as an adventitious primary acceptor when the \"true\" primary acceptor is reduced. Alternatively, the primary acceptor may act in a \"ping-pong\" fashion with respect to subsequent photoelectrons."} {"id": "PMID:168921", "title": "Laser-flash-activated electron paramagnetic resonance studies of primary photochemical reactions in chloroplasts.", "content": "Electron paramagnetic resonance studies of the primary reactants of Photosystems I and II have been conducted at cryogenic temperatures after laser-flash activation with monochromatic light.P-700 photooxidation occurs irreversibly in chloroplasts and in Photosystem I fragments after activation with a 730 nm laser flash at a temperature of 35 degrees K. Flash activation of chloroplasts or Photosystem II chloroplast fragments with 660 nm light results in the production of a free-radical signal (g = 2.002, linewidth approximately 8 gauss) which decays with a half-time of 5.0 ms at 35 degrees K. The half-time of decay is independent of temperature in the range of 10-77 degrees K. This reversible signal can be eliminated by preillumination of the sample at 35 degrees K with 660 nm light (but not by 730 nm light), by preillumination with 660 nm light at room temperature in the presence of 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea (DCMU) plus hydroxylamine, or by adjustment of the oxidation-reduction potential of the chloroplasts to - 150 mV prior to freezing. In the presence of ferricyanide (20-50 mM), two free-radical signals are photoinduced during a 660 nm flash at 35 degrees K. One signal decays with a half-time of 5 ms, whereas the second signal is formed irreversibly. These results are discussed in terms of a current model for the Photosystem II primary reaction at low temperature which postulates a back-reaction between P-680+ and the primary electron acceptor.", "contents": "Laser-flash-activated electron paramagnetic resonance studies of primary photochemical reactions in chloroplasts. Electron paramagnetic resonance studies of the primary reactants of Photosystems I and II have been conducted at cryogenic temperatures after laser-flash activation with monochromatic light.P-700 photooxidation occurs irreversibly in chloroplasts and in Photosystem I fragments after activation with a 730 nm laser flash at a temperature of 35 degrees K. Flash activation of chloroplasts or Photosystem II chloroplast fragments with 660 nm light results in the production of a free-radical signal (g = 2.002, linewidth approximately 8 gauss) which decays with a half-time of 5.0 ms at 35 degrees K. The half-time of decay is independent of temperature in the range of 10-77 degrees K. This reversible signal can be eliminated by preillumination of the sample at 35 degrees K with 660 nm light (but not by 730 nm light), by preillumination with 660 nm light at room temperature in the presence of 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea (DCMU) plus hydroxylamine, or by adjustment of the oxidation-reduction potential of the chloroplasts to - 150 mV prior to freezing. In the presence of ferricyanide (20-50 mM), two free-radical signals are photoinduced during a 660 nm flash at 35 degrees K. One signal decays with a half-time of 5 ms, whereas the second signal is formed irreversibly. These results are discussed in terms of a current model for the Photosystem II primary reaction at low temperature which postulates a back-reaction between P-680+ and the primary electron acceptor."} {"id": "PMID:168922", "title": "Stereospecificity of hydrogen transfer by phosphoglycerate dehydrogenase.", "content": "Phosphoglycerate dehydrogenase (EC 1.1.1.95) has been shown to be A site specific in its hydrogen transfer capacity unlike other dehydrogenases which use phosphorylated substrates. The experiments have been carried out using a coupled assay system with yeast alcohol dehydrogenase. The specific activity measurements of the reaction products indicate the possible influence of an isotope effect on this system.", "contents": "Stereospecificity of hydrogen transfer by phosphoglycerate dehydrogenase. Phosphoglycerate dehydrogenase (EC 1.1.1.95) has been shown to be A site specific in its hydrogen transfer capacity unlike other dehydrogenases which use phosphorylated substrates. The experiments have been carried out using a coupled assay system with yeast alcohol dehydrogenase. The specific activity measurements of the reaction products indicate the possible influence of an isotope effect on this system."} {"id": "PMID:168923", "title": "Further characterization of bovine thyroid prostaglandin synthase.", "content": "1. Prostaglandin synthase activity (EC 1.14.99.1) was demonstrated in bovine thyroid homogenates. 2. The synthase was characterized and shares many characteristics of the well-studied seminal vesicle enzyme and can be inhibited by indomethacin and eicosa-5,8,11,14-tetraynoic acid. 3. The enzyme is localized in the microsomal fraction and is probably associated with the plasma membranes. 4. Thyrotropin, but no other hormone tested, increased the activity of the enzyme when added to a microsomal fraction obtained from bovine thyroid. This effect is tissue-specific since thyrotropin has no effect on bovine seminal esicle or lung prostaglandin synthase. 5. Thyrotropin, cyclic AMP and the phosphodiesterase inhibitors, theophylline and quazodine increase enzyme activity when preincubated with bovine thyroid slices. 6. EDTA, when included in the pre-incubation mixture, enhances the thyrotropin effect on the enzyme but not the cyclic AMP, theophylline, or quazodine augmentation of enzyme activity in bovine thyroid slices. This suggests that phospholipase A is involved in the thyrotropin stimulation of prostaglandin formation.", "contents": "Further characterization of bovine thyroid prostaglandin synthase. 1. Prostaglandin synthase activity (EC 1.14.99.1) was demonstrated in bovine thyroid homogenates. 2. The synthase was characterized and shares many characteristics of the well-studied seminal vesicle enzyme and can be inhibited by indomethacin and eicosa-5,8,11,14-tetraynoic acid. 3. The enzyme is localized in the microsomal fraction and is probably associated with the plasma membranes. 4. Thyrotropin, but no other hormone tested, increased the activity of the enzyme when added to a microsomal fraction obtained from bovine thyroid. This effect is tissue-specific since thyrotropin has no effect on bovine seminal esicle or lung prostaglandin synthase. 5. Thyrotropin, cyclic AMP and the phosphodiesterase inhibitors, theophylline and quazodine increase enzyme activity when preincubated with bovine thyroid slices. 6. EDTA, when included in the pre-incubation mixture, enhances the thyrotropin effect on the enzyme but not the cyclic AMP, theophylline, or quazodine augmentation of enzyme activity in bovine thyroid slices. This suggests that phospholipase A is involved in the thyrotropin stimulation of prostaglandin formation."} {"id": "PMID:168924", "title": "A reactive arginine in adenylate kinase.", "content": "Adenylate kinase (ATP:AMP phosphotransferase, EV 2.7.4.3) from pig heart is inactivated by the specific arginyl reagent phenylglyoxal. During inactivation two molecules of phenyglyoxal are incorporated into the protein indicating the modification of one of the 11 arginine residues. The modification of other amino acids is ruled out. Chemical modification of this essential residue is prevented by high concentrations of the substrates AMP, ADP and MgATP2-. The protection of the substrates is explained by the formation of a ternary abortive enzyme-substrate complex ESS. The dissociation constants KD = [ES] - [S]/[ESS] are determined from the kinetic data of inactivation and protection.", "contents": "A reactive arginine in adenylate kinase. Adenylate kinase (ATP:AMP phosphotransferase, EV 2.7.4.3) from pig heart is inactivated by the specific arginyl reagent phenylglyoxal. During inactivation two molecules of phenyglyoxal are incorporated into the protein indicating the modification of one of the 11 arginine residues. The modification of other amino acids is ruled out. Chemical modification of this essential residue is prevented by high concentrations of the substrates AMP, ADP and MgATP2-. The protection of the substrates is explained by the formation of a ternary abortive enzyme-substrate complex ESS. The dissociation constants KD = [ES] - [S]/[ESS] are determined from the kinetic data of inactivation and protection."} {"id": "PMID:168925", "title": "A physical explanation of the EPR spectrum observed during catalysis by enzymes utilizing coenzyme B12.", "content": "We have proposed that the \"doublet\" EPR spectra observed during catalysis by a number of coenzyme B12-requiring enzymes arises from a weak electrostatic exchange interaction between an organic free radical and low spin Co(II), B12r. By varying the magnitude of the exchange of coupling we have quite accurately simulated the published EPR spectra from the enzyme systems: diol dehydrase, glycerol dehydrase, ribonucleotide reductase, and ethanolamine ammon-ia lyase. A dipolar model was shown to be incompatible with the observed properties of these systems.", "contents": "A physical explanation of the EPR spectrum observed during catalysis by enzymes utilizing coenzyme B12. We have proposed that the \"doublet\" EPR spectra observed during catalysis by a number of coenzyme B12-requiring enzymes arises from a weak electrostatic exchange interaction between an organic free radical and low spin Co(II), B12r. By varying the magnitude of the exchange of coupling we have quite accurately simulated the published EPR spectra from the enzyme systems: diol dehydrase, glycerol dehydrase, ribonucleotide reductase, and ethanolamine ammon-ia lyase. A dipolar model was shown to be incompatible with the observed properties of these systems."} {"id": "PMID:168926", "title": "Isolation and characterization of the plasma membrane of L-1210 cells. Iodination as a marker for the plasma membrane.", "content": "Mouse leukemia L-1210 cells were iodinated with 125I; this permitted the development of a method for the isolation of the plasma membranes. These show a 10- to 16-fold increase in the specific activity of 125I over that of the cell homogenate and a 20-fold increase in the specific activities of 5'-nucleotidase and alkaline phosphatase; 20-fold increase in the specific activities of 5'-nucleotidase and alkaline phosphatase; no mitochondrial or microsomal marker enzyme activities were detected. Sodium dodecyl sulfate gel electrophoresis of the plasma membranes shows approx. 40 peptides with molecular weights ranging from 10 000 to over 200 000; a polypeptide (Mr 50 000) predominates. Of 13 iodinated surface membrane proteins, the major radioactive peptide has a molecular weight of 85 000. The importance of the selection of the appropriate gel system for the analysis of membrane proteins is emphasized.", "contents": "Isolation and characterization of the plasma membrane of L-1210 cells. Iodination as a marker for the plasma membrane. Mouse leukemia L-1210 cells were iodinated with 125I; this permitted the development of a method for the isolation of the plasma membranes. These show a 10- to 16-fold increase in the specific activity of 125I over that of the cell homogenate and a 20-fold increase in the specific activities of 5'-nucleotidase and alkaline phosphatase; 20-fold increase in the specific activities of 5'-nucleotidase and alkaline phosphatase; no mitochondrial or microsomal marker enzyme activities were detected. Sodium dodecyl sulfate gel electrophoresis of the plasma membranes shows approx. 40 peptides with molecular weights ranging from 10 000 to over 200 000; a polypeptide (Mr 50 000) predominates. Of 13 iodinated surface membrane proteins, the major radioactive peptide has a molecular weight of 85 000. The importance of the selection of the appropriate gel system for the analysis of membrane proteins is emphasized."} {"id": "PMID:168927", "title": "Modulation of the distribution of plasma membrane intramembranous particles in contact-inhibited and transformed cells.", "content": "The intrinsic organization of the plasma membrane differs in normal and transformed cells. With the technique of freeze fracture and electron microscopy contact inhibited 3T3 cells have been shown to contain aggregated plasma membrane intramembranous particles, while transformed cells demonstrate a uniform particle distribution. The distribution of intramembrous particles in transformed cells can be affected by colchicine or vinblastine which induces a dose- and time-dependent particle aggregation. These observations suggest that microtubules and other membrane-associated colchicine-sensitive proteins probably influence the distribution of intrinsic membrane proteins and intramembranous particles in nucleated mammalian cells. An aggregated particle distribution has been observed in 3T3 cells or colchicine-treated transformed cells frozen in media, phosphate-buffered saline or following brief exposure to glycerol, sucrose or dimethyl sulfoxide containing solutions, independent of whether specimens were rapidly frozen from 37 degrees C, room temperature or 4 degrees C incubations. Cells briefly stabilized in 1% formaldehyde yields similar patterns of particle distribution as cells rapidly frozen in media or cryoprotectants. Glutaraldehyde fixation of cells, however, appears to alter the fracturing process in these cells, as visualized by an altered fracture face appearance, decreased numbers of particles, and no particle aggregates. Differences in membrane organization between normal and transformed cells have therefore been demonstrated using a series of preparative methods and colchicine and vinblastine have been shown to modulate intramembranous particle distribution in transformed 3T3 cells.", "contents": "Modulation of the distribution of plasma membrane intramembranous particles in contact-inhibited and transformed cells. The intrinsic organization of the plasma membrane differs in normal and transformed cells. With the technique of freeze fracture and electron microscopy contact inhibited 3T3 cells have been shown to contain aggregated plasma membrane intramembranous particles, while transformed cells demonstrate a uniform particle distribution. The distribution of intramembrous particles in transformed cells can be affected by colchicine or vinblastine which induces a dose- and time-dependent particle aggregation. These observations suggest that microtubules and other membrane-associated colchicine-sensitive proteins probably influence the distribution of intrinsic membrane proteins and intramembranous particles in nucleated mammalian cells. An aggregated particle distribution has been observed in 3T3 cells or colchicine-treated transformed cells frozen in media, phosphate-buffered saline or following brief exposure to glycerol, sucrose or dimethyl sulfoxide containing solutions, independent of whether specimens were rapidly frozen from 37 degrees C, room temperature or 4 degrees C incubations. Cells briefly stabilized in 1% formaldehyde yields similar patterns of particle distribution as cells rapidly frozen in media or cryoprotectants. Glutaraldehyde fixation of cells, however, appears to alter the fracturing process in these cells, as visualized by an altered fracture face appearance, decreased numbers of particles, and no particle aggregates. Differences in membrane organization between normal and transformed cells have therefore been demonstrated using a series of preparative methods and colchicine and vinblastine have been shown to modulate intramembranous particle distribution in transformed 3T3 cells."} {"id": "PMID:168928", "title": "Fluid lipid fraction in rod outer segment membrane.", "content": "Rod outer segment membrane is analyzed using the spin resonance label technique by means of two probes. The solubility of the first label,2,2,6,6-tetramethylpiperidin-1-oxyl, is correlated with the membrane fluidity which is measured using a stearic acid spin probe. The two values are compared to the solubility-fluidity relationship which characterizes a model system in which all lipids are in a fluid state. The analysis leads to the conclusion that only two thirds of the membrane lipids are fluid. This conclusion is reinforced by the observation that partial lipid removal leaves rigid lipids associated with the rhodopsin molecules.", "contents": "Fluid lipid fraction in rod outer segment membrane. Rod outer segment membrane is analyzed using the spin resonance label technique by means of two probes. The solubility of the first label,2,2,6,6-tetramethylpiperidin-1-oxyl, is correlated with the membrane fluidity which is measured using a stearic acid spin probe. The two values are compared to the solubility-fluidity relationship which characterizes a model system in which all lipids are in a fluid state. The analysis leads to the conclusion that only two thirds of the membrane lipids are fluid. This conclusion is reinforced by the observation that partial lipid removal leaves rigid lipids associated with the rhodopsin molecules."} {"id": "PMID:168929", "title": "Interactions of lectins with (Na+ + K+)-ATPase of eel electric organ.", "content": "Interaction of lectins with a detergent-solubilized ATPase from eel electric organ was studied. Concanavalin A, which binds to alpha-mannosides, altered the rate of enzyme migration in agar and inhibited the formation of an antigen-antibody precipitate: other lectins had no such effects. Concanavalin A similar amounts partially inhibited (Na+ + K+)-ATPase; this inhibition was reversible by alpha-methylglucoside. There was no corresponding effect of concanavalin A on the potassium p-nitrophenylphosphatase. Concanavalin A also did not interfere with ouabain binding. Thus, concanavalin A binds to an antigenic region also involved in Na+ and/or ATP binding, but does not interact with a K+ site.", "contents": "Interactions of lectins with (Na+ + K+)-ATPase of eel electric organ. Interaction of lectins with a detergent-solubilized ATPase from eel electric organ was studied. Concanavalin A, which binds to alpha-mannosides, altered the rate of enzyme migration in agar and inhibited the formation of an antigen-antibody precipitate: other lectins had no such effects. Concanavalin A similar amounts partially inhibited (Na+ + K+)-ATPase; this inhibition was reversible by alpha-methylglucoside. There was no corresponding effect of concanavalin A on the potassium p-nitrophenylphosphatase. Concanavalin A also did not interfere with ouabain binding. Thus, concanavalin A binds to an antigenic region also involved in Na+ and/or ATP binding, but does not interact with a K+ site."} {"id": "PMID:168930", "title": "Stimulated phosphorylation of non-histone phosphoproteins in SV-40 transformed WI-38 human diploid fibroblasts.", "content": "Because the phosphorylation of non-histone proteins has been suggested to play a role in the regulation of eukaryotic gene transcription, we have compared the phosphorylation of these proteins in normal and SV-40 transformed WI-38 human diploid fibroblasts. The rate of phosphorylation was found to be roughly ten-fold higher in the transformed cells, and this striking difference could not be accounted for by either an increased rate of phosphate transport or by the synthesis of new species of non-histone proteins which subsequently become phosphorylated. To our knowledge this is the most dramatic alteration in non-histone protein phosphorylation ever described, and therefore may have important implications for our understanding of malignant transformation.", "contents": "Stimulated phosphorylation of non-histone phosphoproteins in SV-40 transformed WI-38 human diploid fibroblasts. Because the phosphorylation of non-histone proteins has been suggested to play a role in the regulation of eukaryotic gene transcription, we have compared the phosphorylation of these proteins in normal and SV-40 transformed WI-38 human diploid fibroblasts. The rate of phosphorylation was found to be roughly ten-fold higher in the transformed cells, and this striking difference could not be accounted for by either an increased rate of phosphate transport or by the synthesis of new species of non-histone proteins which subsequently become phosphorylated. To our knowledge this is the most dramatic alteration in non-histone protein phosphorylation ever described, and therefore may have important implications for our understanding of malignant transformation."} {"id": "PMID:168931", "title": "A vascular permeability factor in lymphocyte culture supernants from patients with nephrotic syndrome. II. Pharmacological and physicochemical properties.", "content": "Pharmacological properties of the \"Skin Reactive Factor\" demonstrated in nephrotic patients are similar to guinea-pig Skin Reactive Factor. This biological activity is not antagonized by anti-histaminic and anti-serotonin drugs. It is inhibited by meclofenamate and pyridinolcanbamate. It is enhanced by diethyldithiocarbamate and normal human serum. According to this results it could be an activator of the kinin system. Biochemical studies indicate that it is a pepsin destroyed protein, unaffected by Rnase and Dnase. Its electrophoretic mobility is that of an albumin or an alpha1 globulin.", "contents": "A vascular permeability factor in lymphocyte culture supernants from patients with nephrotic syndrome. II. Pharmacological and physicochemical properties. Pharmacological properties of the \"Skin Reactive Factor\" demonstrated in nephrotic patients are similar to guinea-pig Skin Reactive Factor. This biological activity is not antagonized by anti-histaminic and anti-serotonin drugs. It is inhibited by meclofenamate and pyridinolcanbamate. It is enhanced by diethyldithiocarbamate and normal human serum. According to this results it could be an activator of the kinin system. Biochemical studies indicate that it is a pepsin destroyed protein, unaffected by Rnase and Dnase. Its electrophoretic mobility is that of an albumin or an alpha1 globulin."} {"id": "PMID:168932", "title": "Mathematical analysis of multienzyme systems. I. Modelling of the glycolysis of human erythrocytes.", "content": "A mathematical model for the glycolysis of human erythrocytes is presented which takes into account ATP-synthesis and -consumption. A set of three differential equations describes the steady states and the time-dependent changes of the metabolite concentrations under blood storage conditions. For a given parameter combination there are in general three stationary points of the system, one of which is unstable. At a low ATP-need the ATP-level is relatively constant for variations in the rate constant of the ATP-consuming processes. Above a critical level of the energy consumption the system breaks down. An important role of the 2.3P2G-bypass of the erythrocytes is its action as an \"energy buffer\", wasting ATP in case of ATP-overproduction and producing ATP in case of underproduction. A parameter combination consistent with the data on the isolated enzymes was found which gives a good agreement of theoretical predictions with the measured metabolite concentrations. Under blood preservation conditions the difference of the rates of ATP-production and -consumption is the most important factor for a high ATP-level over long periods.", "contents": "Mathematical analysis of multienzyme systems. I. Modelling of the glycolysis of human erythrocytes. A mathematical model for the glycolysis of human erythrocytes is presented which takes into account ATP-synthesis and -consumption. A set of three differential equations describes the steady states and the time-dependent changes of the metabolite concentrations under blood storage conditions. For a given parameter combination there are in general three stationary points of the system, one of which is unstable. At a low ATP-need the ATP-level is relatively constant for variations in the rate constant of the ATP-consuming processes. Above a critical level of the energy consumption the system breaks down. An important role of the 2.3P2G-bypass of the erythrocytes is its action as an \"energy buffer\", wasting ATP in case of ATP-overproduction and producing ATP in case of underproduction. A parameter combination consistent with the data on the isolated enzymes was found which gives a good agreement of theoretical predictions with the measured metabolite concentrations. Under blood preservation conditions the difference of the rates of ATP-production and -consumption is the most important factor for a high ATP-level over long periods."} {"id": "PMID:168933", "title": "The response of oscillating glycolysis to perturbations in the NADH/NAD system: a comparison between experiments and a computer model.", "content": "The glycolytic pathway is described by a set of coupled non linear differential equations of first order with respect to time. The individual terms of these equations consist of enzyme velocities assuming a steady state hypothesis for the enzymatic forms. These are specified and the system is solved numerically. Oscillations are explained by interaction of PFK with the adenylate system. The conditions for the occurrence of oscillations are tested in a series of computer runs. The phase relations between intermediates of the model agree with those found in yeast cells. As an application of the model the disturbation of oscillations by the addition of acetaldehyde is simulated. The predictions of the model agree with experimental results.", "contents": "The response of oscillating glycolysis to perturbations in the NADH/NAD system: a comparison between experiments and a computer model. The glycolytic pathway is described by a set of coupled non linear differential equations of first order with respect to time. The individual terms of these equations consist of enzyme velocities assuming a steady state hypothesis for the enzymatic forms. These are specified and the system is solved numerically. Oscillations are explained by interaction of PFK with the adenylate system. The conditions for the occurrence of oscillations are tested in a series of computer runs. The phase relations between intermediates of the model agree with those found in yeast cells. As an application of the model the disturbation of oscillations by the addition of acetaldehyde is simulated. The predictions of the model agree with experimental results."} {"id": "PMID:168935", "title": "A negative control model of hormone receptor interaction.", "content": "An original model of hormone-receptor interaction is proposed: the hormone would interact with its receptor by dissociating a regulatory unit from a catalytic unit, which, freed from the negative constraint exerted by the regulatory unit, would become active. It is shown that such a model shares some features with negatively cooperative models: 1. Scatchard plot has a hyperbolic shape; 2. Dissociation of bound labeled hormone, promoted by chemical dilution is enhanced by an excess of cold hormone. A new graph, in which the ratio between the square of bound hormone concentration and the free hormone concentration is plotted against the bound hormone concentration, allows a discrimination between both models. Moreover, the behavior of a negatively controlled receptor unlike a negatively cooperative one, is critically dependent on its physical state (soluble or particulate). The possible application of this model to hormone responsive adenylate cyclases and other biochemical systems, such as cAMP dependent protein kinases, is mentioned.", "contents": "A negative control model of hormone receptor interaction. An original model of hormone-receptor interaction is proposed: the hormone would interact with its receptor by dissociating a regulatory unit from a catalytic unit, which, freed from the negative constraint exerted by the regulatory unit, would become active. It is shown that such a model shares some features with negatively cooperative models: 1. Scatchard plot has a hyperbolic shape; 2. Dissociation of bound labeled hormone, promoted by chemical dilution is enhanced by an excess of cold hormone. A new graph, in which the ratio between the square of bound hormone concentration and the free hormone concentration is plotted against the bound hormone concentration, allows a discrimination between both models. Moreover, the behavior of a negatively controlled receptor unlike a negatively cooperative one, is critically dependent on its physical state (soluble or particulate). The possible application of this model to hormone responsive adenylate cyclases and other biochemical systems, such as cAMP dependent protein kinases, is mentioned."} {"id": "PMID:168937", "title": "Importance of the so-called 'other' sexually-transmitted diseases.", "content": "(1) Some data are presented concerning the frequency and potential morbidity of sexually-transmitted organisms other than T. pallidum or N. gonorrhoeae. (2) Most of the diseases with which these organisms are associated are more prevalent than syphilis and some, at least in one sex, are as common as gonorrhoea. A number appear to carry considerable morbidity, which in the case of Type II herpes virus--if it is responsible for cervical cancer--may ultimately cause more fatalities than syphilis. (3) It is concluded: (a) that, if syphilis and gonorrhoea were reduced to the point of representing no public health concern, many other sexually-transmitted conditions would still remain to pose significant problems: and (b) that health education and other methods of prevention should, where possible, be designed to take into consideration the epidemiological implications of the other organisms listed.", "contents": "Importance of the so-called 'other' sexually-transmitted diseases. (1) Some data are presented concerning the frequency and potential morbidity of sexually-transmitted organisms other than T. pallidum or N. gonorrhoeae. (2) Most of the diseases with which these organisms are associated are more prevalent than syphilis and some, at least in one sex, are as common as gonorrhoea. A number appear to carry considerable morbidity, which in the case of Type II herpes virus--if it is responsible for cervical cancer--may ultimately cause more fatalities than syphilis. (3) It is concluded: (a) that, if syphilis and gonorrhoea were reduced to the point of representing no public health concern, many other sexually-transmitted conditions would still remain to pose significant problems: and (b) that health education and other methods of prevention should, where possible, be designed to take into consideration the epidemiological implications of the other organisms listed."} {"id": "PMID:168938", "title": "Cytomegalovirus in female patients attending a VD clinic.", "content": "A study of 531 female patients attending a venereal disease clinic was undertaken to assess the incidence of cytomegalovirus (CMV) in the cervix. The findings were as follows: (1) 35 of 531 patients had positive cervical cultures for CMV (6-6 per cent.). (2) 28 of 531 patients were positive for Herpes virus hominis (5-3 per cent.). (3) Excluding those who were pregnant, 20 of 28 with CMV were taking oral contraceptives (71 per cent.). (4) Seven babies born to infected mothers showed no signs of cytomegalic inclusion disease. (5) 28 of 35 with CMV had associated genital infections (80 per cent.). (6) Positive cultures were obtained in twenty cases for periods up to 10 months. (7) The CMV complement-fixation test was positive in all 23 patients with positive CMV cultures who were tested. (8) Seven male consorts were examined but CMV was not isolated from any of them. (9) A case of CMV mononucleosis was detected. It is suggested that the higher incidence in patients attending a VD clinic is due to the presence of CMV in the cervix predisposing to other genital infections rather than to its being sexually transmitted.", "contents": "Cytomegalovirus in female patients attending a VD clinic. A study of 531 female patients attending a venereal disease clinic was undertaken to assess the incidence of cytomegalovirus (CMV) in the cervix. The findings were as follows: (1) 35 of 531 patients had positive cervical cultures for CMV (6-6 per cent.). (2) 28 of 531 patients were positive for Herpes virus hominis (5-3 per cent.). (3) Excluding those who were pregnant, 20 of 28 with CMV were taking oral contraceptives (71 per cent.). (4) Seven babies born to infected mothers showed no signs of cytomegalic inclusion disease. (5) 28 of 35 with CMV had associated genital infections (80 per cent.). (6) Positive cultures were obtained in twenty cases for periods up to 10 months. (7) The CMV complement-fixation test was positive in all 23 patients with positive CMV cultures who were tested. (8) Seven male consorts were examined but CMV was not isolated from any of them. (9) A case of CMV mononucleosis was detected. It is suggested that the higher incidence in patients attending a VD clinic is due to the presence of CMV in the cervix predisposing to other genital infections rather than to its being sexually transmitted."} {"id": "PMID:168939", "title": "Control of sleep states in the rat by short light-dark cycles.", "content": "The effects of 60-60 min light-dark (LD) cycles on sleep, feeding, drinking and motor activity were investigated in the rat. Waking, consummatory behaviour and motor activity were inhibited by light, while sleep was enhanced. The effects were dependent on the intensity of light. The percentage of slow wave sleep (SS) increased within the first 15 min of the light period and reached a plateau within 30 min. The reduction of SS during darkness showed a similar time-course. The percentage of paradoxical sleep (PS) started to increase only 15 min after the onset of light and continued to rise during the first 15 min of darkness. All parameters exhibited a free-running circadian rhythm. The LD-induced changes of SS were largest during the circadian phase in which the animal was active. The changes of PS which succeeded the onset or offset of light, were largest in the inactive circadian phase. The most immediate influence of changes in illumination is exerted on the slow wave component of sleep. Hypotheses to account for the temporary dissociation between the two sleep states are discussed.", "contents": "Control of sleep states in the rat by short light-dark cycles. The effects of 60-60 min light-dark (LD) cycles on sleep, feeding, drinking and motor activity were investigated in the rat. Waking, consummatory behaviour and motor activity were inhibited by light, while sleep was enhanced. The effects were dependent on the intensity of light. The percentage of slow wave sleep (SS) increased within the first 15 min of the light period and reached a plateau within 30 min. The reduction of SS during darkness showed a similar time-course. The percentage of paradoxical sleep (PS) started to increase only 15 min after the onset of light and continued to rise during the first 15 min of darkness. All parameters exhibited a free-running circadian rhythm. The LD-induced changes of SS were largest during the circadian phase in which the animal was active. The changes of PS which succeeded the onset or offset of light, were largest in the inactive circadian phase. The most immediate influence of changes in illumination is exerted on the slow wave component of sleep. Hypotheses to account for the temporary dissociation between the two sleep states are discussed."} {"id": "PMID:168940", "title": "The relation of hippocampal theta activity to arousal, attentive behaviour and somato-motor movements in unrestrained cats.", "content": "EEG recordings of hippocampal theta activity and neocortical activity were correlated with direct observations and photographic recordings of the behaviour of unrestrained cats. The behaviour studied included (1) both spontaneous and induced changes in level of arousal (sleep-wakefulness), (2) different types of orienting activity that occur as the animal is repeatedly exposed to a novel environment, and (3) activities such as walking, drinking, and grooming. With increases in arousal, amount of hippocampal theta activity increased in direct association with extent of pupillary dilatation, degree of eye opening, and extent of neocortical desynchronization. Conversely, with spontaneous or habituation-induced reductions of arousal, amount of hippocampal theta activity became reduced. Maximal hippocampal theta activity was associated with the increased eye movement phase of REM sleep and, during wakefulness, with fixed staring and visual searching behaviour ('tonic' orienting activity). In contrast, hippocampal theta activity was suppressed or attenuated during reflexive head turning ('phasic' orienting behaviour) and other stereotyped movements such as drinking, grooming and undirected locomotor activity unaccompanied by attentive behaviour. These results suggest that theta activity is primarily related to arousal and its control by attentional mechanisms.", "contents": "The relation of hippocampal theta activity to arousal, attentive behaviour and somato-motor movements in unrestrained cats. EEG recordings of hippocampal theta activity and neocortical activity were correlated with direct observations and photographic recordings of the behaviour of unrestrained cats. The behaviour studied included (1) both spontaneous and induced changes in level of arousal (sleep-wakefulness), (2) different types of orienting activity that occur as the animal is repeatedly exposed to a novel environment, and (3) activities such as walking, drinking, and grooming. With increases in arousal, amount of hippocampal theta activity increased in direct association with extent of pupillary dilatation, degree of eye opening, and extent of neocortical desynchronization. Conversely, with spontaneous or habituation-induced reductions of arousal, amount of hippocampal theta activity became reduced. Maximal hippocampal theta activity was associated with the increased eye movement phase of REM sleep and, during wakefulness, with fixed staring and visual searching behaviour ('tonic' orienting activity). In contrast, hippocampal theta activity was suppressed or attenuated during reflexive head turning ('phasic' orienting behaviour) and other stereotyped movements such as drinking, grooming and undirected locomotor activity unaccompanied by attentive behaviour. These results suggest that theta activity is primarily related to arousal and its control by attentional mechanisms."} {"id": "PMID:168941", "title": "Postfacial palsy phenomena: faulty nerve regeneration or ephaptic transmission?", "content": "Certain postfacial palsy phenomena--'facial contracture', 'crocodile tears', etc.--have been examined in relation to faulty misrouting of the nerve fibers, which thus far has been offered as an explanation for such phenomena. Analogy is made with the problem of hemifacial spasm, occurring without antecedant facial palsy. It is seen that the two conditions have many things in common and are amenable to similar methods of therapy--such as surgical decompression of the facial nerve without interrupting its fibers or by pharmacological blocking of the facial nerve. Evidence is presented to support the thesis that both the hemifacial spasm and the postfacial palsy phenomena (and a number of other neurological disorders) are due to formation of an 'artificial synapse' (an ephapse) at the site of nerve injury. This would allow for crossing over of impulses from one nerve fiber to another and interaction between afferent and efferent axons, analogous to the situation of bare, uninsulated electrical wires plac", "contents": "Postfacial palsy phenomena: faulty nerve regeneration or ephaptic transmission? Certain postfacial palsy phenomena--'facial contracture', 'crocodile tears', etc.--have been examined in relation to faulty misrouting of the nerve fibers, which thus far has been offered as an explanation for such phenomena. Analogy is made with the problem of hemifacial spasm, occurring without antecedant facial palsy. It is seen that the two conditions have many things in common and are amenable to similar methods of therapy--such as surgical decompression of the facial nerve without interrupting its fibers or by pharmacological blocking of the facial nerve. Evidence is presented to support the thesis that both the hemifacial spasm and the postfacial palsy phenomena (and a number of other neurological disorders) are due to formation of an 'artificial synapse' (an ephapse) at the site of nerve injury. This would allow for crossing over of impulses from one nerve fiber to another and interaction between afferent and efferent axons, analogous to the situation of bare, uninsulated electrical wires plac"} {"id": "PMID:168942", "title": "An electrotonically coupled pathway in the central nervous system of some teleost fish, Gymnotidae and Mormyridae.", "content": "Morphological and physiological results indicate that the magnocellular mesencephalic nucleus (MMN) is characteristic of all species of weakly electric fish, so far investigated. The potentials recorded from this nucleus are due to the fish's own electric organ discharge (EOD). After abolition of the EOD by curare the mesencephalic potential is suppressed, but it can still be obtained by artificial electric stimulation. After injection of curare the medullary pacemaker activity responsible for the EOD remains undisturbed. The results, therefore, let us exclude the hypothesis that the mesencephalic response is evoked by recurrent pacemaker activity. The very short delay (1 msec) of the mesencephalic potential is explained by the existence of a rapid conduction electrosensory pathway where the peripheral, rhombencephalic and mesencephalic elements are electrotonically coupled. This kind of transmission provides a constant synaptic delay and a one-to-one input-output ratio. The fish can receive, by means of this electrosensory pathway, a binary signal for each electrical event whether it comes from its own electric organ or from neighbouring fish.", "contents": "An electrotonically coupled pathway in the central nervous system of some teleost fish, Gymnotidae and Mormyridae. Morphological and physiological results indicate that the magnocellular mesencephalic nucleus (MMN) is characteristic of all species of weakly electric fish, so far investigated. The potentials recorded from this nucleus are due to the fish's own electric organ discharge (EOD). After abolition of the EOD by curare the mesencephalic potential is suppressed, but it can still be obtained by artificial electric stimulation. After injection of curare the medullary pacemaker activity responsible for the EOD remains undisturbed. The results, therefore, let us exclude the hypothesis that the mesencephalic response is evoked by recurrent pacemaker activity. The very short delay (1 msec) of the mesencephalic potential is explained by the existence of a rapid conduction electrosensory pathway where the peripheral, rhombencephalic and mesencephalic elements are electrotonically coupled. This kind of transmission provides a constant synaptic delay and a one-to-one input-output ratio. The fish can receive, by means of this electrosensory pathway, a binary signal for each electrical event whether it comes from its own electric organ or from neighbouring fish."} {"id": "PMID:168945", "title": "A genetic analysis of adult mortality in Leghorn by heavy-breed reciprocal crosses.", "content": "1. Genetic mechanisms of resistance to disease in 1930 pullets and 296 cockerels were investigated by using a Leghorn line (G), a heavy-breed line (H), and their reciprocal crosses G x H and H x G plus two synthetic lines, GnH and HnG which were segregating for line-intact Z chromosomes. 2. The most frequent cause of death was leukosis. 3. Gmale x Hfemale pullets had a significantly higher adult mortality (40-9%) than the reciprocal cross (27-3%). 4. A direct effect of the Z sex chromosome on the incidence of leukosis or on total adult mortality could not be demonstrated. 5. Maternal breed effects and heterosis were relatively more important than Z sex chromosome and autosomal breed effects as causes of both leukosis and total laying house mortality. 6. The heavy-breed line had higher cellular resistance to the leukosis/sarcoma virus subgroups A and B than did the Leghorn line.", "contents": "A genetic analysis of adult mortality in Leghorn by heavy-breed reciprocal crosses. 1. Genetic mechanisms of resistance to disease in 1930 pullets and 296 cockerels were investigated by using a Leghorn line (G), a heavy-breed line (H), and their reciprocal crosses G x H and H x G plus two synthetic lines, GnH and HnG which were segregating for line-intact Z chromosomes. 2. The most frequent cause of death was leukosis. 3. Gmale x Hfemale pullets had a significantly higher adult mortality (40-9%) than the reciprocal cross (27-3%). 4. A direct effect of the Z sex chromosome on the incidence of leukosis or on total adult mortality could not be demonstrated. 5. Maternal breed effects and heterosis were relatively more important than Z sex chromosome and autosomal breed effects as causes of both leukosis and total laying house mortality. 6. The heavy-breed line had higher cellular resistance to the leukosis/sarcoma virus subgroups A and B than did the Leghorn line."} {"id": "PMID:168946", "title": "Dietary aureomycin and the response of the fowl to stressors.", "content": "1. Conventional or gnotobiotic chicks, when injected from 1 d to 3 weeks of age with adrenocorticotrophic hormone (120IU/kg, three times weekly), showed a depressed growth rate, adrenal hypertrophy and depletion of cholesterol form the adrenal glands. 2. Feeding a diet supplemented with aureomycin (10 mg/kg) did not have any consistent ameliorating effect on the response of the stressed bird as judged by the above parameters. 3. It was found that treating germfree chicks with five daily injections of sterile milk on days 3 to 7 did not depress growth rate at any time, nor could differences in adrenal size or cholesterol stores be detected at the end of the 21-d experimental period. The responses were not modified by feeding an aureomycin-supplemented diet.", "contents": "Dietary aureomycin and the response of the fowl to stressors. 1. Conventional or gnotobiotic chicks, when injected from 1 d to 3 weeks of age with adrenocorticotrophic hormone (120IU/kg, three times weekly), showed a depressed growth rate, adrenal hypertrophy and depletion of cholesterol form the adrenal glands. 2. Feeding a diet supplemented with aureomycin (10 mg/kg) did not have any consistent ameliorating effect on the response of the stressed bird as judged by the above parameters. 3. It was found that treating germfree chicks with five daily injections of sterile milk on days 3 to 7 did not depress growth rate at any time, nor could differences in adrenal size or cholesterol stores be detected at the end of the 21-d experimental period. The responses were not modified by feeding an aureomycin-supplemented diet."} {"id": "PMID:168948", "title": "Analysis of O2'-methylnucleoside 5'-phosphates in snake venom hydrolysates of RNA: identification of O2'-methyl-5-carboxymethyluridine as a constituent of yeast transfer RNA.", "content": "Snake venom phosphodiesterase liberates the O2-methylnucleoside (Nm) constituents of RNA as the corresponding 5-nucleotides (PNm), which, in contrast to normal 5-nucleotides (pN), are resistant to dephosphorylation by venom 5-nucleotidase. This property provides the basis of a convenient and highly reproducible quantitative assay for Nm residues in RNA. The assay method involves: (1) hydrolysis of RNA with whole or partially-purified snake venom; (2) isolation of the pNm derivatives, as a group, by anion-exchange chromatography on DEAE-cellulose; (3) resolution of the individual pNm compounds by two-dimensional paper chromatography; (4) identification and quantitative measurement of pNm derivatives by ultraviolet absorption spectrophotometry. Using this procedure, the molar proportions of the Nm constituents of wheat embryo, yeast, and Escherichia coli tRNA have been determined. The close correspondence between the values measured by venom hydrolysis and those obtained by analysis of alkali-stable dinucleotide (Nm-Np) sequences attests to the validity of the venom assay, and further indicates that alkali-stable sequences larger than dinucleotides are not present in significant amounts in the tRNA of the above three organisms. During the present investigation, several ultraviolet-absorbing components, not immediately identifiable as ribose-methylated nucleotides, were isolated along with the expected O2-methylnucleoside 5-phosphates. Preliminary characterization of one of these compounds suggests that it is a derivative of a novel nucleoside, O2-methyl-5-carboxymethyluridine (cm5Um is released as part of an alkali-stable dinucleotide, cm5Um-Ap. The proportion of pU-2 in venom hydrolysates of yeast tRNA (0.02 mol percent, the same as the content of cm5Um-Ap in alkaline hydrolysates) suggests that O2-methyl-5-carboxymethyluridine may be confined to a single isoaccepting species of tRNA in yeast. In an allied study, reinvestigation of the alkali-stable dinucleotide sequences of baker's yeast tRNA has confirmed previous results concerning the sequence distribution of O2-methylribose in yeast tRNA (Gray, M. W. & Lane, B.G. (1967) Biochim. Biophys. Acta 134, 243-257).", "contents": "Analysis of O2'-methylnucleoside 5'-phosphates in snake venom hydrolysates of RNA: identification of O2'-methyl-5-carboxymethyluridine as a constituent of yeast transfer RNA. Snake venom phosphodiesterase liberates the O2-methylnucleoside (Nm) constituents of RNA as the corresponding 5-nucleotides (PNm), which, in contrast to normal 5-nucleotides (pN), are resistant to dephosphorylation by venom 5-nucleotidase. This property provides the basis of a convenient and highly reproducible quantitative assay for Nm residues in RNA. The assay method involves: (1) hydrolysis of RNA with whole or partially-purified snake venom; (2) isolation of the pNm derivatives, as a group, by anion-exchange chromatography on DEAE-cellulose; (3) resolution of the individual pNm compounds by two-dimensional paper chromatography; (4) identification and quantitative measurement of pNm derivatives by ultraviolet absorption spectrophotometry. Using this procedure, the molar proportions of the Nm constituents of wheat embryo, yeast, and Escherichia coli tRNA have been determined. The close correspondence between the values measured by venom hydrolysis and those obtained by analysis of alkali-stable dinucleotide (Nm-Np) sequences attests to the validity of the venom assay, and further indicates that alkali-stable sequences larger than dinucleotides are not present in significant amounts in the tRNA of the above three organisms. During the present investigation, several ultraviolet-absorbing components, not immediately identifiable as ribose-methylated nucleotides, were isolated along with the expected O2-methylnucleoside 5-phosphates. Preliminary characterization of one of these compounds suggests that it is a derivative of a novel nucleoside, O2-methyl-5-carboxymethyluridine (cm5Um is released as part of an alkali-stable dinucleotide, cm5Um-Ap. The proportion of pU-2 in venom hydrolysates of yeast tRNA (0.02 mol percent, the same as the content of cm5Um-Ap in alkaline hydrolysates) suggests that O2-methyl-5-carboxymethyluridine may be confined to a single isoaccepting species of tRNA in yeast. In an allied study, reinvestigation of the alkali-stable dinucleotide sequences of baker's yeast tRNA has confirmed previous results concerning the sequence distribution of O2-methylribose in yeast tRNA (Gray, M. W. & Lane, B.G. (1967) Biochim. Biophys. Acta 134, 243-257)."} {"id": "PMID:168949", "title": "Nutritional control of differentiation (sclerotization) of the myxomycete Physarum flavicomum.", "content": "During differentiation (sclerotization) of the Myxomycete Physarum flavicomum, the acellular phasmodium converts into numerous dormant cells surrounded by cell walls. This work establishes that a condition of nutrient imbalance triggers the differentiation process. Specifically, the unavailability of an adequate spectrum of amino acids in the medium initiates the metabolic and morphological alterations characteristic of the sclerotizing plasmodium. In the absence of extracellular amino acids, the cellular pool of amino acids and cellular protein were catabolized as differentiation proceeded. The pattern of amino acids in the cellular pool also changed during differentiation, as the content of pool amino acids was reduced at least 75 percent. The decrease in protein content was negligible after 12 h incubation but was about 40 percent at 48 h when differentiation was complete. However, in the presence of extracellular amino acids, protein degradation, amino acid pool depletion, and differentiation were all inhibited. Ammonium ions (12.4 mM) similarly delayed differentiation. Differentiation, amino acid pool depletion, and the degradation of cellular protein readily occurred in the presence of an extracellular supply of dextrose, which stimulated cell wall formation. The effect of dimethyl sulfoxide, cyclic 3'-5'-adenosine monophosphate, glutathione, diamide, and other compounds on the differentiation process are reported also.", "contents": "Nutritional control of differentiation (sclerotization) of the myxomycete Physarum flavicomum. During differentiation (sclerotization) of the Myxomycete Physarum flavicomum, the acellular phasmodium converts into numerous dormant cells surrounded by cell walls. This work establishes that a condition of nutrient imbalance triggers the differentiation process. Specifically, the unavailability of an adequate spectrum of amino acids in the medium initiates the metabolic and morphological alterations characteristic of the sclerotizing plasmodium. In the absence of extracellular amino acids, the cellular pool of amino acids and cellular protein were catabolized as differentiation proceeded. The pattern of amino acids in the cellular pool also changed during differentiation, as the content of pool amino acids was reduced at least 75 percent. The decrease in protein content was negligible after 12 h incubation but was about 40 percent at 48 h when differentiation was complete. However, in the presence of extracellular amino acids, protein degradation, amino acid pool depletion, and differentiation were all inhibited. Ammonium ions (12.4 mM) similarly delayed differentiation. Differentiation, amino acid pool depletion, and the degradation of cellular protein readily occurred in the presence of an extracellular supply of dextrose, which stimulated cell wall formation. The effect of dimethyl sulfoxide, cyclic 3'-5'-adenosine monophosphate, glutathione, diamide, and other compounds on the differentiation process are reported also."} {"id": "PMID:168950", "title": "Two forms of a mitochondrial endonuclease in Neurospora crassa.", "content": "Mitochondrial nuclease activity in Neurospora crassa occurs in membrane-bound and soluble forms in approximately equal proportions. These activities apparently are due to the same enzyme, which has an approximate molecular weight of 120 000. A portion of the insoluble enzyme appears to be associated with the inner mitochondrial membrane and is resistant to solubilization by detergent treatment as well as by physical disruption methods.", "contents": "Two forms of a mitochondrial endonuclease in Neurospora crassa. Mitochondrial nuclease activity in Neurospora crassa occurs in membrane-bound and soluble forms in approximately equal proportions. These activities apparently are due to the same enzyme, which has an approximate molecular weight of 120 000. A portion of the insoluble enzyme appears to be associated with the inner mitochondrial membrane and is resistant to solubilization by detergent treatment as well as by physical disruption methods."} {"id": "PMID:168951", "title": "Mortality among patients treated for alcoholism: a 5-year follow-up.", "content": "During a 5-year follow-up of 154 male and female patients treated for alcoholism at the Donwood Institute, 22 deaths were recorded--almost 4 times the expected number. Typical causes were accidents, suicide, cirrhosis of the liver, cancers of the upper digestive and respiratory tracts and ischemic heart disease. Compared with other samples of alcoholics, unusually few deaths occurred during the first 2 years of follow-up, which suggests the importance of the post-treatment attention given to these patients and the need to greatly extend the duration of aftercare.", "contents": "Mortality among patients treated for alcoholism: a 5-year follow-up. During a 5-year follow-up of 154 male and female patients treated for alcoholism at the Donwood Institute, 22 deaths were recorded--almost 4 times the expected number. Typical causes were accidents, suicide, cirrhosis of the liver, cancers of the upper digestive and respiratory tracts and ischemic heart disease. Compared with other samples of alcoholics, unusually few deaths occurred during the first 2 years of follow-up, which suggests the importance of the post-treatment attention given to these patients and the need to greatly extend the duration of aftercare."} {"id": "PMID:168952", "title": "Autonomic neuropathy and carcinoma of the lung.", "content": "A patient who died from oat-cell carcinoma of the lung had had abdominal pain and obstipation. Autopsy revealed autonomic neuropathy limited to the gastrointestinal tract, which was considered to be related to carcinoma as a remote effect. This interpretation was further supported by the presence of Wallerian degeneration of the dorsal columns. Autonomic neuropathy involving the gastrointestinal tract in association with malignant disease has not been previously described.", "contents": "Autonomic neuropathy and carcinoma of the lung. A patient who died from oat-cell carcinoma of the lung had had abdominal pain and obstipation. Autopsy revealed autonomic neuropathy limited to the gastrointestinal tract, which was considered to be related to carcinoma as a remote effect. This interpretation was further supported by the presence of Wallerian degeneration of the dorsal columns. Autonomic neuropathy involving the gastrointestinal tract in association with malignant disease has not been previously described."} {"id": "PMID:168953", "title": "An unusual beta-cell adenoma.", "content": "An unusual case of insulinoma in a 51-year-old man demonstrates the difficulties in diagnosing and treating hypoglycemia. From the many laboratory tests and procedures performed, the only findings typical of insulinoma were inappropriate values of plasma immunoreactive insulin in relation to the corresponding values of blood glucose, and these were sporadic. A small beta-cell adenoma in the pancreatic head was the cause of the hypoglycemia.", "contents": "An unusual beta-cell adenoma. An unusual case of insulinoma in a 51-year-old man demonstrates the difficulties in diagnosing and treating hypoglycemia. From the many laboratory tests and procedures performed, the only findings typical of insulinoma were inappropriate values of plasma immunoreactive insulin in relation to the corresponding values of blood glucose, and these were sporadic. A small beta-cell adenoma in the pancreatic head was the cause of the hypoglycemia."} {"id": "PMID:168954", "title": "Tumors of childhood in Ibadan, Nigeria.", "content": "Childhood cancer is fast becoming an important pediatric problem in several parts of Africa, with the progressive decline of infectious and nutritional diseases. The present study analyzes 1325 Nigerian children with neoplasms diagnosed over a 13-year period (1960-1972). It accounted for 12.5% of all tumors registered in our Cancer Registery over the period of study. The commonest type of malignant tumor in the Nigerian child was solid lymphoma, of which Burkitt's tumor predominated. The overall pattern of tumors in these children was strikingly different in certain aspects from what obtains in the Caucasian child. When four main groups of tumors were considered, the ratio frequency pattern in Nigerian children was one of high lymphoma, high orbital, low leukemia, low glioma type. In the Caucasian child, the ratio frequency pattern is usually one of high leukemia, high glioma, low lymphoma, low orbital type. The observed differences in frequencies of childhood tumors between population groups require further studies.", "contents": "Tumors of childhood in Ibadan, Nigeria. Childhood cancer is fast becoming an important pediatric problem in several parts of Africa, with the progressive decline of infectious and nutritional diseases. The present study analyzes 1325 Nigerian children with neoplasms diagnosed over a 13-year period (1960-1972). It accounted for 12.5% of all tumors registered in our Cancer Registery over the period of study. The commonest type of malignant tumor in the Nigerian child was solid lymphoma, of which Burkitt's tumor predominated. The overall pattern of tumors in these children was strikingly different in certain aspects from what obtains in the Caucasian child. When four main groups of tumors were considered, the ratio frequency pattern in Nigerian children was one of high lymphoma, high orbital, low leukemia, low glioma type. In the Caucasian child, the ratio frequency pattern is usually one of high leukemia, high glioma, low lymphoma, low orbital type. The observed differences in frequencies of childhood tumors between population groups require further studies."} {"id": "PMID:168955", "title": "Pancreatic neoplasms in an animal model: morphological, biological, and comparative studies.", "content": "After a short latency (15 weeks), a 100% incidence of pancreatic neoplasms was induced in Syrian golden hamsters, following the administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN). Data extracted from reports of human pancreatic neoplasms were compared with findings relative to the induced neoplasms. The latter resembled human pancreatic tumors, in both biological and morphological aspects.", "contents": "Pancreatic neoplasms in an animal model: morphological, biological, and comparative studies. After a short latency (15 weeks), a 100% incidence of pancreatic neoplasms was induced in Syrian golden hamsters, following the administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN). Data extracted from reports of human pancreatic neoplasms were compared with findings relative to the induced neoplasms. The latter resembled human pancreatic tumors, in both biological and morphological aspects."} {"id": "PMID:168956", "title": "Tubular carcinoma of the male breast: report of a case.", "content": "Tubular carcinoma of the male breast is a rare neoplasm which may have a biological behavior comparable to its counterpart in females. A case of male tubular carcinoma treated by radical mastectomy and postoperative irradiation is reported. There was a metastasis to one axillary lymph node at the time of diagnosis. No associated areas of intraductal or infiltrating scirrhous carcinoma were found. Microscopic gynecomastia was present. The patient is alive and well 8 years postoperatively.", "contents": "Tubular carcinoma of the male breast: report of a case. Tubular carcinoma of the male breast is a rare neoplasm which may have a biological behavior comparable to its counterpart in females. A case of male tubular carcinoma treated by radical mastectomy and postoperative irradiation is reported. There was a metastasis to one axillary lymph node at the time of diagnosis. No associated areas of intraductal or infiltrating scirrhous carcinoma were found. Microscopic gynecomastia was present. The patient is alive and well 8 years postoperatively."} {"id": "PMID:168957", "title": "Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes.", "content": "In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast.", "contents": "Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes. In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast."} {"id": "PMID:168958", "title": "Nonchromaffin paraganglioma (chemodectoma) of thyroid region.", "content": "A case of a paraganglioma located over the thyroid cartilage in the midline is reported. The tumor had all the appearances of a carotid body tumor, but its odd location could not be explained on the basis of previously known areas where paraganglionic tissues have been found. Since a paraganglioma has also hitherto been described within the thyroid gland, clinicians and pathologists alike are cautioned that unusually located paragangliomas may be expected in the future.", "contents": "Nonchromaffin paraganglioma (chemodectoma) of thyroid region. A case of a paraganglioma located over the thyroid cartilage in the midline is reported. The tumor had all the appearances of a carotid body tumor, but its odd location could not be explained on the basis of previously known areas where paraganglionic tissues have been found. Since a paraganglioma has also hitherto been described within the thyroid gland, clinicians and pathologists alike are cautioned that unusually located paragangliomas may be expected in the future."} {"id": "PMID:168959", "title": "The unique association of mammary stromal sarcoma with intraductal carcinoma.", "content": "The unique combination of clinically unsuspected stromal sarcoma and noninfiltrating intraductal mammary carcinoma is presented. This association has not been previously documented. The clinicopathologic features of cystosarcoma phyllodes and mammary stromal sarcoma are reviewed to provide background perspectives to illuminate the unusual aspects of this case.", "contents": "The unique association of mammary stromal sarcoma with intraductal carcinoma. The unique combination of clinically unsuspected stromal sarcoma and noninfiltrating intraductal mammary carcinoma is presented. This association has not been previously documented. The clinicopathologic features of cystosarcoma phyllodes and mammary stromal sarcoma are reviewed to provide background perspectives to illuminate the unusual aspects of this case."} {"id": "PMID:168960", "title": "Current status of estrogen receptors in human breast cancer.", "content": "In estrogen target tissues and hormone-dependent tumors, the steroid enters the cells and binds to a cytoplasmic protein called the estrogen receptor (ER). The steroid-receptor complex then migrates to the nuclei, where it initiates the biochemicial events characteristic of estrogen stimulation. Since ER is absent in tissues not responsive to estrogen, recent studies have asked whether ER assays in human breast cancer tissue might be used to identify those patients likely to respond to endocrine therapy. Data on 436 clinical trials contributed from a dozen centers around the world now clearly indicate that if a patient's tumor does not contain ER, there is virtually no chance of tumor regression following endocrine therapy. A large number of patients can be thus spared unrewarding major endocrine ablative therapy if ER assays are performed routinely. Of tumors with positiev ER, 55-60% respond to endocrine therapy. This single piece of data, when coupled with available clinical prognostic factors such as menopausal status, disease free interval, site of the dominant lesion, and especially response to previous hormonal therapies, should be practicing oncologist to select or reject endocrine therapy with considerable confidence.", "contents": "Current status of estrogen receptors in human breast cancer. In estrogen target tissues and hormone-dependent tumors, the steroid enters the cells and binds to a cytoplasmic protein called the estrogen receptor (ER). The steroid-receptor complex then migrates to the nuclei, where it initiates the biochemicial events characteristic of estrogen stimulation. Since ER is absent in tissues not responsive to estrogen, recent studies have asked whether ER assays in human breast cancer tissue might be used to identify those patients likely to respond to endocrine therapy. Data on 436 clinical trials contributed from a dozen centers around the world now clearly indicate that if a patient's tumor does not contain ER, there is virtually no chance of tumor regression following endocrine therapy. A large number of patients can be thus spared unrewarding major endocrine ablative therapy if ER assays are performed routinely. Of tumors with positiev ER, 55-60% respond to endocrine therapy. This single piece of data, when coupled with available clinical prognostic factors such as menopausal status, disease free interval, site of the dominant lesion, and especially response to previous hormonal therapies, should be practicing oncologist to select or reject endocrine therapy with considerable confidence."} {"id": "PMID:168961", "title": "Clinical management of advanced gastrointestinal cancer.", "content": "Although advanced gastrointestinal cancer is the most commonplace problem encountered by the medical oncologist, this group of diseases has proved exceedingly resistant to past chemotherapy efforts. 5-Fluorouracil (5-FU), accepted by some as standard treatment, had provided only infrequent, incomplete, and fleeting antitumor effects, which are probably more than counterbalanced by its gastrointestinal, mucocutaneous, and hematologic antihost effects. There is no evidence that any manipulation of route or schedule of administration provides any improvement in the therapeutic ratio of 5-FU. There is no evidence that this drug contributes to patient survival when used at any stage of any type of gastrointestinal carcinoma. The search for alternative single drugs to 5-FU has been disappointing. The nitrosoureas and Mitomycin C produce occasional regressions, but they do not match the meager effectiveness of 5-FU; and they, in addition, present the difficult problem of cumulative bone marrow suppression. Recent trials with combination regimens have given some indication that the long stalemate in chemotherapy of gastrointestinal cancer may be breaking. Substantial improvements in frequency of tumor regression have been recorded for gastric carcinoma with combinations of 5-FU and BCNU, 5-FU and methyl CCNU, and 5-FU, Mitomycin C, and cytosine arabinoside; for colorectal carcinoma, with the combination of 5-FU, methyl CCNU, and vincristine; and for carcinoid tumors and islet cell carcinomas, with the combination of 5-FU and Streptozotocin. There are also suggestion that such combination chemotherapy with response rates in the 30 to 50% range may produce increased survival when compared to the untreated patient and patients treated with single-drug regimens. While the accomplishments of chemotherapy for the gastrointestinal cancer patient remain less than spectacular there is nevertheless realistic hope that a respectable contribution can now be made to multidisciplinary efforts applied at a stage of disease with minimal tumor burden.", "contents": "Clinical management of advanced gastrointestinal cancer. Although advanced gastrointestinal cancer is the most commonplace problem encountered by the medical oncologist, this group of diseases has proved exceedingly resistant to past chemotherapy efforts. 5-Fluorouracil (5-FU), accepted by some as standard treatment, had provided only infrequent, incomplete, and fleeting antitumor effects, which are probably more than counterbalanced by its gastrointestinal, mucocutaneous, and hematologic antihost effects. There is no evidence that any manipulation of route or schedule of administration provides any improvement in the therapeutic ratio of 5-FU. There is no evidence that this drug contributes to patient survival when used at any stage of any type of gastrointestinal carcinoma. The search for alternative single drugs to 5-FU has been disappointing. The nitrosoureas and Mitomycin C produce occasional regressions, but they do not match the meager effectiveness of 5-FU; and they, in addition, present the difficult problem of cumulative bone marrow suppression. Recent trials with combination regimens have given some indication that the long stalemate in chemotherapy of gastrointestinal cancer may be breaking. Substantial improvements in frequency of tumor regression have been recorded for gastric carcinoma with combinations of 5-FU and BCNU, 5-FU and methyl CCNU, and 5-FU, Mitomycin C, and cytosine arabinoside; for colorectal carcinoma, with the combination of 5-FU, methyl CCNU, and vincristine; and for carcinoid tumors and islet cell carcinomas, with the combination of 5-FU and Streptozotocin. There are also suggestion that such combination chemotherapy with response rates in the 30 to 50% range may produce increased survival when compared to the untreated patient and patients treated with single-drug regimens. While the accomplishments of chemotherapy for the gastrointestinal cancer patient remain less than spectacular there is nevertheless realistic hope that a respectable contribution can now be made to multidisciplinary efforts applied at a stage of disease with minimal tumor burden."} {"id": "PMID:168962", "title": "Future prospects for immunotherapy.", "content": "The use of immunotherapy for the treatment of cancer is in its infancy. Definitive examples currently exist in both experimental animals and in humans that immunotherapy can beneficially affect the natural course of established growing malignant disease. Whether these pioneering examples will be extended so that immunotherapy can have a broad applicability in the treatment of cancer in man in not yet known and is a subject of much current work.", "contents": "Future prospects for immunotherapy. The use of immunotherapy for the treatment of cancer is in its infancy. Definitive examples currently exist in both experimental animals and in humans that immunotherapy can beneficially affect the natural course of established growing malignant disease. Whether these pioneering examples will be extended so that immunotherapy can have a broad applicability in the treatment of cancer in man in not yet known and is a subject of much current work."} {"id": "PMID:168963", "title": "Correction of a murine mammary tumor virus-associated immunological depression by selective immunosuppression with cytosine arabinoside.", "content": "Mammary tumor virus (MTV) infection has been shown to be associated with a diminished hypersensitive reaction to methylated bovine serum albumin. Since methylated bovine serum albumin-induced hypersensitivity appears to be a mixed [humoral versus cell-mediated immunity (CMI)] reaction, the deficit in reactivity could be caused by, among other things, a direct depression of CMI or an increase in a humoral, blocking component. Assay of oxazolone-induced contact sensitivity and phytohemagglutinin-induced lymphocyte stimulation revealed normal or greater than normal CMI in MTV-positive animals. Treatment of MTV-positive and -negative animals with a regimen of cytosine arabinoside designed to inhibit only humoral immunity and leave CMI intact, corrected the deficit in methylated bovine serum albumin reactivity in MTV-positive mice. Thus, it is suggested that MTV infection may facilitate the production of interfering or blocking humoral immunity.", "contents": "Correction of a murine mammary tumor virus-associated immunological depression by selective immunosuppression with cytosine arabinoside. Mammary tumor virus (MTV) infection has been shown to be associated with a diminished hypersensitive reaction to methylated bovine serum albumin. Since methylated bovine serum albumin-induced hypersensitivity appears to be a mixed [humoral versus cell-mediated immunity (CMI)] reaction, the deficit in reactivity could be caused by, among other things, a direct depression of CMI or an increase in a humoral, blocking component. Assay of oxazolone-induced contact sensitivity and phytohemagglutinin-induced lymphocyte stimulation revealed normal or greater than normal CMI in MTV-positive animals. Treatment of MTV-positive and -negative animals with a regimen of cytosine arabinoside designed to inhibit only humoral immunity and leave CMI intact, corrected the deficit in methylated bovine serum albumin reactivity in MTV-positive mice. Thus, it is suggested that MTV infection may facilitate the production of interfering or blocking humoral immunity."} {"id": "PMID:168964", "title": "Failure to detect anti-group-specific murine leukemia virus activity in tetraparental AKR-CBA chimeras.", "content": "Tetraparental AKR-CBA/H-T6 chimeras were primarily derived and investigated to determine whether factors associated with the tumor resistance of the CBA/H-T6 could overcome the innate lymphoma susceptibility of the AKR. Evidence has since shown that, on comparison with the AKR, lymphomas were not only delayed but were also less common in a group of 18 early embryo aggregation derived AKR-CBA/H-T6 tetraparental chimeras. Evidence here has shown other clear differences between the AKR and AKR-CBA/H-T6 chimeras. Whereas murine group-specific murine leukemia viral antigens were detected in the sera in both situations, immunoabsorption studies showed that, in the AKR, the antigens exist complexed to the corresponding antibodies. The situation in the chimeras was in complete contrast, since here antigens exist as a \"free\" form. This in turn has led us to suggest that the advantage in respect to tumor immunity in the AKR-CBA/H-T6 chimeras is due to the tolerance to oncogenic virus being maintained. In this situation and in contrast to the AKR, in the absence of \"masking\" antibody-viral antigenic complexes, \"normal\" tumor immunity can be effected. It has to be assumed that tolerance to the oncogenic Gross virus in the AKR-CBA/H-T6 chimeras reflects the influence of the CBA component. How this has possibly been achieved is discussed.", "contents": "Failure to detect anti-group-specific murine leukemia virus activity in tetraparental AKR-CBA chimeras. Tetraparental AKR-CBA/H-T6 chimeras were primarily derived and investigated to determine whether factors associated with the tumor resistance of the CBA/H-T6 could overcome the innate lymphoma susceptibility of the AKR. Evidence has since shown that, on comparison with the AKR, lymphomas were not only delayed but were also less common in a group of 18 early embryo aggregation derived AKR-CBA/H-T6 tetraparental chimeras. Evidence here has shown other clear differences between the AKR and AKR-CBA/H-T6 chimeras. Whereas murine group-specific murine leukemia viral antigens were detected in the sera in both situations, immunoabsorption studies showed that, in the AKR, the antigens exist complexed to the corresponding antibodies. The situation in the chimeras was in complete contrast, since here antigens exist as a \"free\" form. This in turn has led us to suggest that the advantage in respect to tumor immunity in the AKR-CBA/H-T6 chimeras is due to the tolerance to oncogenic virus being maintained. In this situation and in contrast to the AKR, in the absence of \"masking\" antibody-viral antigenic complexes, \"normal\" tumor immunity can be effected. It has to be assumed that tolerance to the oncogenic Gross virus in the AKR-CBA/H-T6 chimeras reflects the influence of the CBA component. How this has possibly been achieved is discussed."} {"id": "PMID:168965", "title": "Seroepidemiological evidence for horizontal transmission of bovine C-type virus.", "content": "Thirty colostrum-deprived calves from leukemia-free herds were foster nursed for 10 weeks on cows infected with bovine C-type virus (BLV) from multiple-case herds or on cows from leukemia-free herds. After weaning, the calves were raised in continuous contact with BLV-infected animals of approximately the same ages. Sera collected at 6 to 18 and 43 to 48 months of age were examined for the presence of antibodies to BLV by the immunofluorescent antibody test. At 6 to 18 months of age, only 1 of the 30 calves from leukemia-free herds had a detectable antibody response to BLV. By 43 to 48 months of age the number of antibody-positive animals had risen to 17. The foster dam's herd of origin did not significantly affect the rate of BLV infection. These results indicate that BLV can be horizontally transmitted from infected to noninfected animals.", "contents": "Seroepidemiological evidence for horizontal transmission of bovine C-type virus. Thirty colostrum-deprived calves from leukemia-free herds were foster nursed for 10 weeks on cows infected with bovine C-type virus (BLV) from multiple-case herds or on cows from leukemia-free herds. After weaning, the calves were raised in continuous contact with BLV-infected animals of approximately the same ages. Sera collected at 6 to 18 and 43 to 48 months of age were examined for the presence of antibodies to BLV by the immunofluorescent antibody test. At 6 to 18 months of age, only 1 of the 30 calves from leukemia-free herds had a detectable antibody response to BLV. By 43 to 48 months of age the number of antibody-positive animals had risen to 17. The foster dam's herd of origin did not significantly affect the rate of BLV infection. These results indicate that BLV can be horizontally transmitted from infected to noninfected animals."} {"id": "PMID:168966", "title": "Quantitation of virus-induced (MLr) and normal (Thy.1.2) cell surface antigens in isolated plasma membranes and the extracellular ascites fluid of mouse leukemia cells.", "content": "Plasma membranes were isolated by two methods from mouse leukemia cells containing mammary tumor virus-induced (MLr) and normal (Thy.1.2) antigens on their surfaces. A number of chemical components, enzymic activities, and the antigenic contents were determined in subcellular fractions and found to be specifically concentrated in the plasma membrane fractions. The major part of the cellular MLr, in contrast to Thy.1.2, was present in the 105,000 X gmax supernatant of the cell homogenate. This and other results indicate an easy release of the antigen from the plasma membrane. A considerable amount of MLr was also present in the ascites fluid, partly free and partly bound, supposedly in an immune complex that allowed the isolation of three components of similar molecular weights as mammary tumor virus components. The extracellular presence of MLr may illustrate that, by shedding of antigen, the tumor may protect itself against the immunological defense of the host.", "contents": "Quantitation of virus-induced (MLr) and normal (Thy.1.2) cell surface antigens in isolated plasma membranes and the extracellular ascites fluid of mouse leukemia cells. Plasma membranes were isolated by two methods from mouse leukemia cells containing mammary tumor virus-induced (MLr) and normal (Thy.1.2) antigens on their surfaces. A number of chemical components, enzymic activities, and the antigenic contents were determined in subcellular fractions and found to be specifically concentrated in the plasma membrane fractions. The major part of the cellular MLr, in contrast to Thy.1.2, was present in the 105,000 X gmax supernatant of the cell homogenate. This and other results indicate an easy release of the antigen from the plasma membrane. A considerable amount of MLr was also present in the ascites fluid, partly free and partly bound, supposedly in an immune complex that allowed the isolation of three components of similar molecular weights as mammary tumor virus components. The extracellular presence of MLr may illustrate that, by shedding of antigen, the tumor may protect itself against the immunological defense of the host."} {"id": "PMID:168967", "title": "DNA synthesis in membrane-denuded nuclei and nuclear fractions from host liver and Morris hepatomas.", "content": "Incorporation of [3H]TTP into membrane-denuded nuclei and fractions of these nuclei from host liver and Morris hepatomas has been compared. Treatment of sucrose nuclei with Triton X-100 removed 95% of the phospholipids and 15 to 20% of the protein. These membrane-denuded nuclei remained physically stable. The Triton X-100-extracted nuclei incorporated label into their DNA in nuclear-incorporating system similar to sucrose nuclei with their membranes intact. Triton X-100-treated nuclei from hepatoma 7777 incorporated six times more label and those from hepatoma 7800 incorporated three times more label than Triton X-100-treated host liver nuclei. Nuclei from the three sources incorporated more label when exogenous DNA was added to the incubation system, but the difference in incorporation between the hepatoma nuclei and the host liver nuclei disappeared. When Triton X-100-treated nuclei, prepared from a tumor-bearing animal given injections of [3H]thymidine for 10 min were fractionated on sucrose gradients after disruption by high Mg2+ concentration, the fractions from hepatoma 7777 nuclei contained six times as much label as the host liver nuclear fractions. Nuclear fractions prepared from unabeled hepatomas or host livers had DNA polymerase activity. The activity, however, is the same in fractions prepared from hepatoma 7777 or host liver nuclei. It is suggested that the nuclear membrane does not play an important role in nuclear DNA synthesis. It is further suggested that the increased incorporation found with hepatoma nuclei is dependent on a physical or chemical arrangement of components within the nucleus and not solely on different enzyme levels.", "contents": "DNA synthesis in membrane-denuded nuclei and nuclear fractions from host liver and Morris hepatomas. Incorporation of [3H]TTP into membrane-denuded nuclei and fractions of these nuclei from host liver and Morris hepatomas has been compared. Treatment of sucrose nuclei with Triton X-100 removed 95% of the phospholipids and 15 to 20% of the protein. These membrane-denuded nuclei remained physically stable. The Triton X-100-extracted nuclei incorporated label into their DNA in nuclear-incorporating system similar to sucrose nuclei with their membranes intact. Triton X-100-treated nuclei from hepatoma 7777 incorporated six times more label and those from hepatoma 7800 incorporated three times more label than Triton X-100-treated host liver nuclei. Nuclei from the three sources incorporated more label when exogenous DNA was added to the incubation system, but the difference in incorporation between the hepatoma nuclei and the host liver nuclei disappeared. When Triton X-100-treated nuclei, prepared from a tumor-bearing animal given injections of [3H]thymidine for 10 min were fractionated on sucrose gradients after disruption by high Mg2+ concentration, the fractions from hepatoma 7777 nuclei contained six times as much label as the host liver nuclear fractions. Nuclear fractions prepared from unabeled hepatomas or host livers had DNA polymerase activity. The activity, however, is the same in fractions prepared from hepatoma 7777 or host liver nuclei. It is suggested that the nuclear membrane does not play an important role in nuclear DNA synthesis. It is further suggested that the increased incorporation found with hepatoma nuclei is dependent on a physical or chemical arrangement of components within the nucleus and not solely on different enzyme levels."} {"id": "PMID:168968", "title": "Postreplication repair of alkylation damage to DNA of mammalian cells in culture.", "content": "Incorporation and alkaline sucrose sedimentation studies of DNA from mouse L-cells have demonstrated the following effects of N-methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS). Increasing the concentration of both agents increases the number of single-strand breaks or alkali-labile lesions of existing DNA, which affects the incorporation of [3H]thymidine into DNA by reducing its relative rate. DNA that is newly synthesized during the 1st hr in [3H]thymidine after MNU treatment is of lower molecular weight than is existing DNA with alkali-labile lesions in treated cells and is also lower than DNA synthesized in control cells. Such small segments formed in treated cells are elongated and joined to form high-molecular-weight DNA in the subsequent 4-hr chase in thymidine or 5-bromo-2'-deoxyuridine. Near-ultraviolet photolysis selectively degrades 5-bromo-2'-deoxyuridine-elongated DNA to segments that are nearly as small as those before chase. Further, caffeine (2 mM) present during the thymidine chase prevents nascent-strand elongation, although caffeine-insensitive chain growth occurs partly in MNU-alkylated cells. The MMS lesion (single-strand breakage in alkali) in existing DNA also temporarily interrupts replicative synthesis and makes short segments, but their elongation seems insensitive to caffeine. Our results indicate that MNU may produce both caffeine-sensitive interruptions (probably gaps), as ultraviolet damage does, and apurinic site-directed, caffeine-insensitive interruptions in nascent strands, while MMS may cause exclusively the latter. Further evidence for this is the caffeine potentiation of only MNU killing, like ultraviolet killing, of L-cells. The extent of such a specific MNU lesion is estimated to be no more than 4% of the total extent of methylation, predicting that the lesion that is accessible to caffeine-sensitive repair will be a minor product(s) other than N7-methylguanine. Mutagenic and carcinogenic effects of MNU, which are higher than those of MMS, could be ascribed to such a particular MNU lesion(s) and its repair.", "contents": "Postreplication repair of alkylation damage to DNA of mammalian cells in culture. Incorporation and alkaline sucrose sedimentation studies of DNA from mouse L-cells have demonstrated the following effects of N-methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS). Increasing the concentration of both agents increases the number of single-strand breaks or alkali-labile lesions of existing DNA, which affects the incorporation of [3H]thymidine into DNA by reducing its relative rate. DNA that is newly synthesized during the 1st hr in [3H]thymidine after MNU treatment is of lower molecular weight than is existing DNA with alkali-labile lesions in treated cells and is also lower than DNA synthesized in control cells. Such small segments formed in treated cells are elongated and joined to form high-molecular-weight DNA in the subsequent 4-hr chase in thymidine or 5-bromo-2'-deoxyuridine. Near-ultraviolet photolysis selectively degrades 5-bromo-2'-deoxyuridine-elongated DNA to segments that are nearly as small as those before chase. Further, caffeine (2 mM) present during the thymidine chase prevents nascent-strand elongation, although caffeine-insensitive chain growth occurs partly in MNU-alkylated cells. The MMS lesion (single-strand breakage in alkali) in existing DNA also temporarily interrupts replicative synthesis and makes short segments, but their elongation seems insensitive to caffeine. Our results indicate that MNU may produce both caffeine-sensitive interruptions (probably gaps), as ultraviolet damage does, and apurinic site-directed, caffeine-insensitive interruptions in nascent strands, while MMS may cause exclusively the latter. Further evidence for this is the caffeine potentiation of only MNU killing, like ultraviolet killing, of L-cells. The extent of such a specific MNU lesion is estimated to be no more than 4% of the total extent of methylation, predicting that the lesion that is accessible to caffeine-sensitive repair will be a minor product(s) other than N7-methylguanine. Mutagenic and carcinogenic effects of MNU, which are higher than those of MMS, could be ascribed to such a particular MNU lesion(s) and its repair."} {"id": "PMID:168969", "title": "Some ultrastructural features of the cell surface after SV40 transformation and somatic hybridization with normal untransformed cells.", "content": "We have studied the surface properties of four cell lines: normal human fibroblasts (GM-177), SV40 transformed Lesch-Nyhan fibroblasts (LN-SV), mouse macrophages, and somatic cell hybrids between mouse macrophages and human SV40-transformed fibroblasts (LN-SV). The concanavalin A (Con A)-peroxidase method was used to visualize the localization of the Con A binding sites by means of electron microscopy. The mean thickness of the reaction product was calculated and the distribution pattern was visualized by drawing \"glycograms,\" from which the ratio of covered to uncovered areas was measured. Ruthenium red technique was used to study the ability of the cell surface to retain ruthenium red-positive materials after rinsing in phosphate-buffered saline. Before rinsing, there were no differences between thicknesses of the ruthenium red-positive surface layers of normal and virus-transformed Lesch-Nyhan fibroblasts. After rinsing, however, significant differences in the ability to retain ruthenium red-positive material were seen in favor of the SV40-transformed Lesch-Nyhan fibroblasts (54% over 35%). Before rinsing, significant differences in the thickness of the ruthenium red-positive material were found between mouse macrophages and the hybrids between mouse macrophages and SV40-transformed human fibroblasts, with the hybrids expressing a thicker ruthenium red-positive layer than did the parental mouse macrophages. After washing, however, the ability to retain this material was greater in mouse macrophages than in hybrids. The hybrid cell surface resembles that of SV40-transformed human Lesch-Nyhan fibroblasts. The Con A-peroxidase method shows a different distribution of the reaction product. In general, in all four cases the central portions of the cells had less continuous labeling patterns than did their peripheries, while the marginal portions were very often devoid of the reaction product. Normal human fibroblasts had the most continuous surface reaction product, the thickest reaction product, and the greatest Con A:gap ratio. In all four of these measurements, the hybrid cell line expressed great similarity to the parental cell lines, especially to the mouse macrophages.", "contents": "Some ultrastructural features of the cell surface after SV40 transformation and somatic hybridization with normal untransformed cells. We have studied the surface properties of four cell lines: normal human fibroblasts (GM-177), SV40 transformed Lesch-Nyhan fibroblasts (LN-SV), mouse macrophages, and somatic cell hybrids between mouse macrophages and human SV40-transformed fibroblasts (LN-SV). The concanavalin A (Con A)-peroxidase method was used to visualize the localization of the Con A binding sites by means of electron microscopy. The mean thickness of the reaction product was calculated and the distribution pattern was visualized by drawing \"glycograms,\" from which the ratio of covered to uncovered areas was measured. Ruthenium red technique was used to study the ability of the cell surface to retain ruthenium red-positive materials after rinsing in phosphate-buffered saline. Before rinsing, there were no differences between thicknesses of the ruthenium red-positive surface layers of normal and virus-transformed Lesch-Nyhan fibroblasts. After rinsing, however, significant differences in the ability to retain ruthenium red-positive material were seen in favor of the SV40-transformed Lesch-Nyhan fibroblasts (54% over 35%). Before rinsing, significant differences in the thickness of the ruthenium red-positive material were found between mouse macrophages and the hybrids between mouse macrophages and SV40-transformed human fibroblasts, with the hybrids expressing a thicker ruthenium red-positive layer than did the parental mouse macrophages. After washing, however, the ability to retain this material was greater in mouse macrophages than in hybrids. The hybrid cell surface resembles that of SV40-transformed human Lesch-Nyhan fibroblasts. The Con A-peroxidase method shows a different distribution of the reaction product. In general, in all four cases the central portions of the cells had less continuous labeling patterns than did their peripheries, while the marginal portions were very often devoid of the reaction product. Normal human fibroblasts had the most continuous surface reaction product, the thickest reaction product, and the greatest Con A:gap ratio. In all four of these measurements, the hybrid cell line expressed great similarity to the parental cell lines, especially to the mouse macrophages."} {"id": "PMID:168970", "title": "Sequential histological and histochemical study of the rat liver during aflatoxin B1-induced carcinogenesis.", "content": "Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, succinic dehydrogenase, and alkaline and acid nucleases. No significant lesions occurred before 15 weeks. During this period, the liver was histochemically unchanged except for a periportal decrease of alkaline phosphatase and adenosine triphosphatase. Scattered hepatocytes with a strong glucose-6-phosphatase activity appeared. These changes represent toxic effects of aflatoxin B1 and are irrelevant to carcinogenesis. From 15 weeks onward, three types of liver cell hyperplastic foci and nodules developed. Histologically, and with respect to glycogen, fat, and RNA content, only two of these types were considered as potential precursors of hepatocarcinomas. However, all types exhibited a decrease or absence of the enzymes studied. Both histological and histochemical changes stressed the complex heterogeneity existing between and within hepatic foci and nodules. From 11 months on, hepatocarcinomas developed. The tumors disclosed similar histochemical changes. This similarity further supports the \"precarcinomatous\" nature of hyperplastic foci and nodules. It appears that focal changes in surface as well as in cytoplasmic and nuclear enzymes are intimately and very early linked to the carcinogenic process. Whether they are fundamental or only represent an epiphenomenon remains unclear.", "contents": "Sequential histological and histochemical study of the rat liver during aflatoxin B1-induced carcinogenesis. Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, succinic dehydrogenase, and alkaline and acid nucleases. No significant lesions occurred before 15 weeks. During this period, the liver was histochemically unchanged except for a periportal decrease of alkaline phosphatase and adenosine triphosphatase. Scattered hepatocytes with a strong glucose-6-phosphatase activity appeared. These changes represent toxic effects of aflatoxin B1 and are irrelevant to carcinogenesis. From 15 weeks onward, three types of liver cell hyperplastic foci and nodules developed. Histologically, and with respect to glycogen, fat, and RNA content, only two of these types were considered as potential precursors of hepatocarcinomas. However, all types exhibited a decrease or absence of the enzymes studied. Both histological and histochemical changes stressed the complex heterogeneity existing between and within hepatic foci and nodules. From 11 months on, hepatocarcinomas developed. The tumors disclosed similar histochemical changes. This similarity further supports the \"precarcinomatous\" nature of hyperplastic foci and nodules. It appears that focal changes in surface as well as in cytoplasmic and nuclear enzymes are intimately and very early linked to the carcinogenic process. Whether they are fundamental or only represent an epiphenomenon remains unclear."} {"id": "PMID:168971", "title": "Concanavalin A agglutination of cells from primary hepatocellular carcinomas and hepatic nodules induced by N-2-fluorenylacetamide.", "content": "A previous study demonstrated that cells of transplantable hepatocellular carcinomas were agglutinated by the plant lectin concanavalin A, while normal hepatocytes were not. In the present experiments, 95% or more of cells obtained from primary hepatocellular carcinomas which resulted from exposure of rats to N-2-fluorenylacetamide were agglutinated by this lectin. Exposure to this carcinogen also produces grossly visible foci of morphologically and biochemically altered hepatocytes which have been termed hepatic (hyperplastic; premalignant, neoplastic) nodules. Although these hepatocyte aggregates are generally accepted as precursors of the hepatocellular carcinomas, no agglutination was detected when their cells were exposed to concanavalin A. These results indicate that concanavalin A agglutinability is not acquired as a result of tumor transplantation. Furthermore, they suggest that significant alterations must occur in the cells of hepatic nodules prior to the manifestation of malignant behavior.", "contents": "Concanavalin A agglutination of cells from primary hepatocellular carcinomas and hepatic nodules induced by N-2-fluorenylacetamide. A previous study demonstrated that cells of transplantable hepatocellular carcinomas were agglutinated by the plant lectin concanavalin A, while normal hepatocytes were not. In the present experiments, 95% or more of cells obtained from primary hepatocellular carcinomas which resulted from exposure of rats to N-2-fluorenylacetamide were agglutinated by this lectin. Exposure to this carcinogen also produces grossly visible foci of morphologically and biochemically altered hepatocytes which have been termed hepatic (hyperplastic; premalignant, neoplastic) nodules. Although these hepatocyte aggregates are generally accepted as precursors of the hepatocellular carcinomas, no agglutination was detected when their cells were exposed to concanavalin A. These results indicate that concanavalin A agglutinability is not acquired as a result of tumor transplantation. Furthermore, they suggest that significant alterations must occur in the cells of hepatic nodules prior to the manifestation of malignant behavior."} {"id": "PMID:168973", "title": "Microinjection of thymidine kinase and bovine serum albumin into mammalian cells by fusion with red blood cells.", "content": "A procedure is described by which proteins can be rapidly and efficiently microinjected into large numbers of culture cells. Proteins were first introduced into mammalian red blood cells during hypotonic hemolysis, and the resealed red cells were subsequently fused to culture cells using Sendai virus. In seven experiments, thymidine kinase or 125I-BSA were transferred to culture cells during fusion. Although proteins were used in the present experiments, the microinjection procedure should work equally well for other macromolecules.", "contents": "Microinjection of thymidine kinase and bovine serum albumin into mammalian cells by fusion with red blood cells. A procedure is described by which proteins can be rapidly and efficiently microinjected into large numbers of culture cells. Proteins were first introduced into mammalian red blood cells during hypotonic hemolysis, and the resealed red cells were subsequently fused to culture cells using Sendai virus. In seven experiments, thymidine kinase or 125I-BSA were transferred to culture cells during fusion. Although proteins were used in the present experiments, the microinjection procedure should work equally well for other macromolecules."} {"id": "PMID:168977", "title": "The effect of methylene dimethanesulphonate (MDMS) on the conformation of DNA and its dependence on base composition.", "content": "The interaction of the alkanesulphonate, methylene dimethanesulphonate (MDMS) with DNA has been studied. Thermal denaturation studies on mixtures of MDMS and DNA showed a dose-dependent decrease of the melting temperature midpoint (Tm) of the DNA. In addition, an irreversible decrease in ultraviolet absorption (hypochromism) preceded the hyperchromic shift, the magnitude of the former being linearly related to both the relative concentration of MDMS and the G-C content of the DNA used. Neither the reduction in melting temperature nor the initial UV absorption decrease occurred after dialysis of the reaction mixture. Equimolar proportions of the hydrolysis products of MDMS did not give the same effects as observed with the unhydrolysed agent. A similar hypochromism followed by strand separation occurs when DNA is allowed to stand with MDMS at room temperature, the time of subsequent strand separation being related to the treatment level of the drug. A weak association of MDMS with DNA is considered to be involved resulting in a local compression of the helical structure in the vicinity of the G-C pairs. It is suggested that this conformational change may act as a substrate for repair enzymes in vivo.", "contents": "The effect of methylene dimethanesulphonate (MDMS) on the conformation of DNA and its dependence on base composition. The interaction of the alkanesulphonate, methylene dimethanesulphonate (MDMS) with DNA has been studied. Thermal denaturation studies on mixtures of MDMS and DNA showed a dose-dependent decrease of the melting temperature midpoint (Tm) of the DNA. In addition, an irreversible decrease in ultraviolet absorption (hypochromism) preceded the hyperchromic shift, the magnitude of the former being linearly related to both the relative concentration of MDMS and the G-C content of the DNA used. Neither the reduction in melting temperature nor the initial UV absorption decrease occurred after dialysis of the reaction mixture. Equimolar proportions of the hydrolysis products of MDMS did not give the same effects as observed with the unhydrolysed agent. A similar hypochromism followed by strand separation occurs when DNA is allowed to stand with MDMS at room temperature, the time of subsequent strand separation being related to the treatment level of the drug. A weak association of MDMS with DNA is considered to be involved resulting in a local compression of the helical structure in the vicinity of the G-C pairs. It is suggested that this conformational change may act as a substrate for repair enzymes in vivo."} {"id": "PMID:168978", "title": "The effects of several croton oil constituents on two types of DNA repair and cyclic nucleotide levels in mammalian cells in vitro.", "content": "The purpose of the present study was to determine the effects of two potent tumor-promoting agents on two DNA repair mechanisms and cyclic nucleotide levels in mammalian cells. Human amnion (AV3) cells were treated with low dose levels of either UV of N-acetoxy-acetylaminofluorene. Subsequently, DNA excision repair as measured by unscheduled DNA synthesis was followed in the absence or presence of non-toxic levels of either 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-dibenzoate (PDB), both potent tumor promoters, or phorbol, a non-promoter. Neither of these compounds inhibited DNA repair synthesis occurring in response to low doses of the carcinogenic agents. In addition, TPA did not inhibit \"post-replication repair\" in response to UV irradiation of growing Chinese hamster (V79-4) cells. However, both TPA and PDB did cause rapid dramatic increases in cyclic guanosine monophosphate levels in human amnion cells; phorbol had no effect. Neither of these compounds affected cyclic adenosine monophosphate levels. These results are discussed in the light of a possible mechanism of the action of tumor promoters involving \"post-replication repair\".", "contents": "The effects of several croton oil constituents on two types of DNA repair and cyclic nucleotide levels in mammalian cells in vitro. The purpose of the present study was to determine the effects of two potent tumor-promoting agents on two DNA repair mechanisms and cyclic nucleotide levels in mammalian cells. Human amnion (AV3) cells were treated with low dose levels of either UV of N-acetoxy-acetylaminofluorene. Subsequently, DNA excision repair as measured by unscheduled DNA synthesis was followed in the absence or presence of non-toxic levels of either 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-dibenzoate (PDB), both potent tumor promoters, or phorbol, a non-promoter. Neither of these compounds inhibited DNA repair synthesis occurring in response to low doses of the carcinogenic agents. In addition, TPA did not inhibit \"post-replication repair\" in response to UV irradiation of growing Chinese hamster (V79-4) cells. However, both TPA and PDB did cause rapid dramatic increases in cyclic guanosine monophosphate levels in human amnion cells; phorbol had no effect. Neither of these compounds affected cyclic adenosine monophosphate levels. These results are discussed in the light of a possible mechanism of the action of tumor promoters involving \"post-replication repair\"."} {"id": "PMID:168980", "title": "[Presence of autocomplementary RNA with viral specificity in cells infected with herpes virus].", "content": "RNA from cells infected with Herpes simplex virus contain a higher percentage of double-stranded RNA than non-infected cells. This percentage increases three-fold upon self-annealing. The complementary RNA sequences were shown to be virus-specific by the following criteria: (1) high melting temperature than double-stranded RNA from non infected cells; (2) higher density in caesium sulphate; (3) specific hybridization with viral DNA.", "contents": "[Presence of autocomplementary RNA with viral specificity in cells infected with herpes virus]. RNA from cells infected with Herpes simplex virus contain a higher percentage of double-stranded RNA than non-infected cells. This percentage increases three-fold upon self-annealing. The complementary RNA sequences were shown to be virus-specific by the following criteria: (1) high melting temperature than double-stranded RNA from non infected cells; (2) higher density in caesium sulphate; (3) specific hybridization with viral DNA."} {"id": "PMID:168981", "title": "[Description of the folliculo-stellate cells in the anterior hypophysis of the monkey Macacus irus].", "content": "Folliculo-stellar cells are present in the anterior lobe of hypophysis of the monkey Macacus irus. These cells limit strait cavities in which one can observe microvillosites at the apical pole of the cells. The folliculo-stellar cells possess long and thin fibers which insert themselves between different types of granular cells and sometimes extend to the peri-capillar regions. Numerous organelles are present in these folliculo-stellar cells, especially microfilaments.", "contents": "[Description of the folliculo-stellate cells in the anterior hypophysis of the monkey Macacus irus]. Folliculo-stellar cells are present in the anterior lobe of hypophysis of the monkey Macacus irus. These cells limit strait cavities in which one can observe microvillosites at the apical pole of the cells. The folliculo-stellar cells possess long and thin fibers which insert themselves between different types of granular cells and sometimes extend to the peri-capillar regions. Numerous organelles are present in these folliculo-stellar cells, especially microfilaments."} {"id": "PMID:168982", "title": "[Induction of cutaneous or subcutaneous fibroblastic tumors in the Afghan pika (Ochotona rufescens rufescens) by injection or bovine papilloma virus].", "content": "Newborn Afghan pikas have been inoculated with bovine papilloma virus via the subcutaneous route. Cutaneous or subcutaneous fibromas and fibrosarcomas were observed after a mean incubation period of nine months. The transmission of these tumors by homograft has been obtained. Bovine papilloma virus antibodies have been demonstrated in most of the animals inoculated at birth. They have not been detected in animals bearing transplanted tumors.", "contents": "[Induction of cutaneous or subcutaneous fibroblastic tumors in the Afghan pika (Ochotona rufescens rufescens) by injection or bovine papilloma virus]. Newborn Afghan pikas have been inoculated with bovine papilloma virus via the subcutaneous route. Cutaneous or subcutaneous fibromas and fibrosarcomas were observed after a mean incubation period of nine months. The transmission of these tumors by homograft has been obtained. Bovine papilloma virus antibodies have been demonstrated in most of the animals inoculated at birth. They have not been detected in animals bearing transplanted tumors."} {"id": "PMID:168983", "title": "Secificity of mouse endocervical cell response progesterone: presence of receptors.", "content": "The mouse cervical cell response to progesterone, corticosterone, and androgens was studied in vitro and comparatively by grafts on males. Contrary to the exocervical cells which responded more or less to the three steroid hormones, the endocervical cells responded exclusively to progesterone even in an estrogen free system. This result suggests the existence in the mouse endocervical cells of specific receptors to progesterone and indicates that the squamons cells of the uterine cervix have a different response to steroid hormones depending on where these cells are located.", "contents": "Secificity of mouse endocervical cell response progesterone: presence of receptors. The mouse cervical cell response to progesterone, corticosterone, and androgens was studied in vitro and comparatively by grafts on males. Contrary to the exocervical cells which responded more or less to the three steroid hormones, the endocervical cells responded exclusively to progesterone even in an estrogen free system. This result suggests the existence in the mouse endocervical cells of specific receptors to progesterone and indicates that the squamons cells of the uterine cervix have a different response to steroid hormones depending on where these cells are located."} {"id": "PMID:168984", "title": "[RNA fragments, in vivo inhibitors of Shope fibroma and vaccinia virus multiplication].", "content": "RNA-fragments rich in purine nucleotides and resulting from degradation of ribosomal RNA from E. coli M 500 Sho-R with pancreatic RNase exhibit only in vivo an inhibitory effect on Shope fibroma and vaccinia virus multiplication.", "contents": "[RNA fragments, in vivo inhibitors of Shope fibroma and vaccinia virus multiplication]. RNA-fragments rich in purine nucleotides and resulting from degradation of ribosomal RNA from E. coli M 500 Sho-R with pancreatic RNase exhibit only in vivo an inhibitory effect on Shope fibroma and vaccinia virus multiplication."} {"id": "PMID:168985", "title": "[C-type virus particles in lymphocytes cultured from cows with persistant lymphocytosis. Preliminary results on French cattle stock].", "content": "C type virus particles were shown in cultures of lymphocytes originating from cows with persistent lymphocytosis. These observations on French cattle are in complete accordance with data previously obtained in the USA. Viral replication is highly stimulated by the addition of phytohemagglutinin in the culture medium. Several morphological and biological properties, specific to the bovine virus differentiate this virus from C type viruses of other species.", "contents": "[C-type virus particles in lymphocytes cultured from cows with persistant lymphocytosis. Preliminary results on French cattle stock]. C type virus particles were shown in cultures of lymphocytes originating from cows with persistent lymphocytosis. These observations on French cattle are in complete accordance with data previously obtained in the USA. Viral replication is highly stimulated by the addition of phytohemagglutinin in the culture medium. Several morphological and biological properties, specific to the bovine virus differentiate this virus from C type viruses of other species."} {"id": "PMID:168986", "title": "Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.", "content": "The purpose of this study was to examine the mechanisms underlying adrenergic-cholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measure in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the intropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.", "contents": "Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium. The purpose of this study was to examine the mechanisms underlying adrenergic-cholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measure in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the intropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP."} {"id": "PMID:168987", "title": "Sleep-stage regulation of ventricular arrhythmias in the unanesthetized pig.", "content": "In two groups of purebred juvenile Hampshire pigs, left anterior descending coronary occluders were implanted. The pigs were then adapted to the recording chamber until they would manifest a criterion pattern of sleep while in it. In group A, permanent coronary artery occlusions were produced, and the effects of various sleep stages on the resultant cardiac arrhythmias were observed. Sleep intervals during which transitional and slow wave (SW) sleep alternated were correlated with increased arrhythmias relative to the awake state (P less than 0.04). The increase was maximum during sustained periods of SW sleep. Intervals during which rapid eye movement (REM) sleep predominated were correlated with a reduction in arrhythmias. In group B, temporary occlusions were made during both an awake condition and after criterion patterns of either SW or REM sleep. Occlusions after SW sleep reduced the ventricular fibrillation latency compared with that during the awake control state (P less than 0.05), whereas occlusions after REM sleep increased ventricular fibrillation latency (P less than 0.05). We conclude that SW SLEEP, BUT NOT REM sleep, has a deleterious effect on the ischemic myocardium. REM sleep may have a beneficial effect, since it increases ventricular fibrillation latency. Heart rate changes do not appear to be correlated with the effects of either sleep stage.", "contents": "Sleep-stage regulation of ventricular arrhythmias in the unanesthetized pig. In two groups of purebred juvenile Hampshire pigs, left anterior descending coronary occluders were implanted. The pigs were then adapted to the recording chamber until they would manifest a criterion pattern of sleep while in it. In group A, permanent coronary artery occlusions were produced, and the effects of various sleep stages on the resultant cardiac arrhythmias were observed. Sleep intervals during which transitional and slow wave (SW) sleep alternated were correlated with increased arrhythmias relative to the awake state (P less than 0.04). The increase was maximum during sustained periods of SW sleep. Intervals during which rapid eye movement (REM) sleep predominated were correlated with a reduction in arrhythmias. In group B, temporary occlusions were made during both an awake condition and after criterion patterns of either SW or REM sleep. Occlusions after SW sleep reduced the ventricular fibrillation latency compared with that during the awake control state (P less than 0.05), whereas occlusions after REM sleep increased ventricular fibrillation latency (P less than 0.05). We conclude that SW SLEEP, BUT NOT REM sleep, has a deleterious effect on the ischemic myocardium. REM sleep may have a beneficial effect, since it increases ventricular fibrillation latency. Heart rate changes do not appear to be correlated with the effects of either sleep stage."} {"id": "PMID:168988", "title": "Histochemical and structural changes in human myocardial cells after cardiopulmonary bypass.", "content": "The histochemical and ultrastructural effects of extracorporeal circulation and aortic cross-clamping during coronary heart surgery have been examined in drill biopsy samples of the left ventricle in 22 patients. The biopsies were obtained before and after bypass with a DeSoutter drill. Histochemical studies indicated definite differences between control and experimental biopsies, with increased succinic dehydrogenase, cytochrome oxidase, and LDH activity, while phosphorylase A and myosin ATPase activities declined. Furthermore, free phospholipid levels increased, as determined by the acid hematein reaction. Ultrastructural examination demonstrated loss of glycogen, intracellular swelling, and mitochondrial damage, which included loss of matrix density, loss of cristae, and eventual disruption in the postbypass biopsy. These results, which closely resemble the effects of ischemia and reperfusion observed in animal experiments, suggest that the initial insult is a change in membrane permeability regulation.", "contents": "Histochemical and structural changes in human myocardial cells after cardiopulmonary bypass. The histochemical and ultrastructural effects of extracorporeal circulation and aortic cross-clamping during coronary heart surgery have been examined in drill biopsy samples of the left ventricle in 22 patients. The biopsies were obtained before and after bypass with a DeSoutter drill. Histochemical studies indicated definite differences between control and experimental biopsies, with increased succinic dehydrogenase, cytochrome oxidase, and LDH activity, while phosphorylase A and myosin ATPase activities declined. Furthermore, free phospholipid levels increased, as determined by the acid hematein reaction. Ultrastructural examination demonstrated loss of glycogen, intracellular swelling, and mitochondrial damage, which included loss of matrix density, loss of cristae, and eventual disruption in the postbypass biopsy. These results, which closely resemble the effects of ischemia and reperfusion observed in animal experiments, suggest that the initial insult is a change in membrane permeability regulation."} {"id": "PMID:168990", "title": "Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs.", "content": "To obtain insight into the mechanism(s) responsible for the direct visualization of acute myocardial infarcts by myocardial scintigraphy with technetium-99m stannous pyrophosphate (99mTc-PYP), scintigraphic and morphologic studies were performed in 22 dogs subjected to occlusion of the proximal left anterior descending coronary artery (LAD). Grossly visible myocardial infarcts occurred in ten of 11 dogs with LAD occlusion for one day, five with LAD occlusion for two days, two with LAD occlusion for seven days and two with LAD occlusion for 13 days. Rare, microscopic foci of necrosis were observed in one dog with LAD occlusion for one day, and no lesions were present in two dogs subjected to temporary LAD occlusion for eight minutes and reflow for 24 hours. In the latter three dogs, 99mTc-PYP myocardial scintigrams were negative. In the 19 dogs with gross infarcts, 99mTc-PYP myocardial scintigrams were strongly positive at one and two days after LAD occlusion, much less positive at seven days and faintly positive at 13 days after occlusion. Positive myocardial scintigrams in most showed \"doughnut\" patterns, with marked peripheral concentration of radioactivity around central zones of much lower activity. On histologic examination, the one and two-day-old infarcts exhibited subendocardially located central zones and surrounding peripheral zones, both of which showed distinctive histopathological and histochemical features, including the selective occurrence in the peripheral zones of calcified muscle cells with ultrastructurally demonstrable apatite-like crystals in mitochondria. Selective occurrence of high tissue levels of 99mTc-PYP radioactivity also was demonstrated in the peripheral zones of four infarcts. Hearts with older infarcts (seven and 13 days) showed progressive replacement of necrotic myocardium by granulation tissue and progressive reduction in calcium deposits in the areas of damage. The data obtained in this study establish a temporal and topographical relationship between calcium accumulation in acute myocardial infarcts and 99mTc-PYP uptake responsible for scintigraphic detection of the lesions with this radionuclide in dogs subjected to proximal LAD occlusion.", "contents": "Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs. To obtain insight into the mechanism(s) responsible for the direct visualization of acute myocardial infarcts by myocardial scintigraphy with technetium-99m stannous pyrophosphate (99mTc-PYP), scintigraphic and morphologic studies were performed in 22 dogs subjected to occlusion of the proximal left anterior descending coronary artery (LAD). Grossly visible myocardial infarcts occurred in ten of 11 dogs with LAD occlusion for one day, five with LAD occlusion for two days, two with LAD occlusion for seven days and two with LAD occlusion for 13 days. Rare, microscopic foci of necrosis were observed in one dog with LAD occlusion for one day, and no lesions were present in two dogs subjected to temporary LAD occlusion for eight minutes and reflow for 24 hours. In the latter three dogs, 99mTc-PYP myocardial scintigrams were negative. In the 19 dogs with gross infarcts, 99mTc-PYP myocardial scintigrams were strongly positive at one and two days after LAD occlusion, much less positive at seven days and faintly positive at 13 days after occlusion. Positive myocardial scintigrams in most showed \"doughnut\" patterns, with marked peripheral concentration of radioactivity around central zones of much lower activity. On histologic examination, the one and two-day-old infarcts exhibited subendocardially located central zones and surrounding peripheral zones, both of which showed distinctive histopathological and histochemical features, including the selective occurrence in the peripheral zones of calcified muscle cells with ultrastructurally demonstrable apatite-like crystals in mitochondria. Selective occurrence of high tissue levels of 99mTc-PYP radioactivity also was demonstrated in the peripheral zones of four infarcts. Hearts with older infarcts (seven and 13 days) showed progressive replacement of necrotic myocardium by granulation tissue and progressive reduction in calcium deposits in the areas of damage. The data obtained in this study establish a temporal and topographical relationship between calcium accumulation in acute myocardial infarcts and 99mTc-PYP uptake responsible for scintigraphic detection of the lesions with this radionuclide in dogs subjected to proximal LAD occlusion."} {"id": "PMID:168991", "title": "Determination of phosphodiesterase I activity in human blood serum.", "content": "Phosphodiesterase I (EC 3.1.4.1) activity was detected in normal human blood serum. The enzyme is stable at laboratory temperature for three days, but is inactivated at pH less than 7. The pH for optimum activity increases with the substrate concentration (under the conditions used, from pH 9.0 to 10.2) and, conversely, the Km increases with pH and buffer concentration. The enzyme is inhibited by ethylenediaminetetraacetate but not by phosphate (0.1 mol/liter). We developed a simple quantitative method for its determination, based on hydrolysis of the p-nitrophenyl ester of thymidine 5'-monophosphate and subsequent measurement of the liberated p-nitrophenol at 400 nm in NaOH (0.1 mol/liter). Normal values (mean +/- 2 SD) were determined to be 33 +/- 6.4 U/liter. Preliminary studies indicate that phosphodiesterase I activity is greater than normal in serum of patients with necrotic changes in the liver or kidney or in cases of breast cancer, but not in that of patients with myocardial infarction, bone cancer, lung cancer, or chronic liver cirrhosis.", "contents": "Determination of phosphodiesterase I activity in human blood serum. Phosphodiesterase I (EC 3.1.4.1) activity was detected in normal human blood serum. The enzyme is stable at laboratory temperature for three days, but is inactivated at pH less than 7. The pH for optimum activity increases with the substrate concentration (under the conditions used, from pH 9.0 to 10.2) and, conversely, the Km increases with pH and buffer concentration. The enzyme is inhibited by ethylenediaminetetraacetate but not by phosphate (0.1 mol/liter). We developed a simple quantitative method for its determination, based on hydrolysis of the p-nitrophenyl ester of thymidine 5'-monophosphate and subsequent measurement of the liberated p-nitrophenol at 400 nm in NaOH (0.1 mol/liter). Normal values (mean +/- 2 SD) were determined to be 33 +/- 6.4 U/liter. Preliminary studies indicate that phosphodiesterase I activity is greater than normal in serum of patients with necrotic changes in the liver or kidney or in cases of breast cancer, but not in that of patients with myocardial infarction, bone cancer, lung cancer, or chronic liver cirrhosis."} {"id": "PMID:168992", "title": "Iodine organification defect following treatment of thyrotoxicosis with antithyroid drugs.", "content": "Two patients remained clinically euthyroid following treatment for thyrotoxicosis with antithyroid drugs in spite of persistently elevated thyroid radioiodine uptakes not suppressable by exogenous triiodothyronine. Perchlorate discharge tests showed a defect in the intrathyroidal organification of iodine. Circulating levels of thyroxine were normal. From our study of 105 patients treated for thyrotoxicosis with antithyroid drugs, apparent remission of thyrotoxicosis by this mechanism might occur in up to 2 percent of patients.", "contents": "Iodine organification defect following treatment of thyrotoxicosis with antithyroid drugs. Two patients remained clinically euthyroid following treatment for thyrotoxicosis with antithyroid drugs in spite of persistently elevated thyroid radioiodine uptakes not suppressable by exogenous triiodothyronine. Perchlorate discharge tests showed a defect in the intrathyroidal organification of iodine. Circulating levels of thyroxine were normal. From our study of 105 patients treated for thyrotoxicosis with antithyroid drugs, apparent remission of thyrotoxicosis by this mechanism might occur in up to 2 percent of patients."} {"id": "PMID:168993", "title": "Steroidogenesis in a virilizing ovarian tumour.", "content": "A metabolic study with tissue from a virilizing arrhenoblastoma, using as precursors [7-3H]pregnenolone, [7-3H]17alpha-hydroxypregnenolone,[4-14C]17alpha-hydroxyprogesterone and [4-14C]testosterone, revealed that in spite of a deficient activity of 3beta-hydroxysteroid dehydrogenase-5-isomerase the overall production of testosterone was compensated by an increased activity of a lyase converting [4-14C]17alpha-hydroxyprogesterone to testosterone (via androstenedione) and was comparable to the production obtained by normal ovarian tissue. The masculinizing effects of the tumour in vivo were most probably caused by accumulation of testosterone due to deficiencies in enzymes catabolizing testosterone to 17-ketosteroids and its aromatization to oestrogen. The unique property of the arrhenoblastoma to convert [4-14C]17alpha-hydroxyprogesterone to [4-14C]11-deoxycortisol (Reichstein's compound S) suggests an adrenal origin of the tumour which may explain its limited capacity to aromatize testosterone.", "contents": "Steroidogenesis in a virilizing ovarian tumour. A metabolic study with tissue from a virilizing arrhenoblastoma, using as precursors [7-3H]pregnenolone, [7-3H]17alpha-hydroxypregnenolone,[4-14C]17alpha-hydroxyprogesterone and [4-14C]testosterone, revealed that in spite of a deficient activity of 3beta-hydroxysteroid dehydrogenase-5-isomerase the overall production of testosterone was compensated by an increased activity of a lyase converting [4-14C]17alpha-hydroxyprogesterone to testosterone (via androstenedione) and was comparable to the production obtained by normal ovarian tissue. The masculinizing effects of the tumour in vivo were most probably caused by accumulation of testosterone due to deficiencies in enzymes catabolizing testosterone to 17-ketosteroids and its aromatization to oestrogen. The unique property of the arrhenoblastoma to convert [4-14C]17alpha-hydroxyprogesterone to [4-14C]11-deoxycortisol (Reichstein's compound S) suggests an adrenal origin of the tumour which may explain its limited capacity to aromatize testosterone."} {"id": "PMID:168994", "title": "Early diagnosis of congenital adrenal hyperplasia by measurement of 17-hydroxyprogesterone.", "content": "Plasma 17-hydroxyprogesterone was measured by a simple radioimmunoassay technique in six infants, aged 3 days to 3 months, with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hormonal levels in this group were compared to those of twenty normal newborns and to those found in sixty samples of umbilical vein blood from normal deliveries. Plasma 17-hydroxyprogesterone concentrations were markedly elevated in all congenital adrenal hyperplasia infants (range 544.7-1837 nmol/l, normal 3.03-19.06) at a time when urinary studies in some of these were either not diagnostic or inconclusive. In one infant whose cord blood was analysed, the level was also greatly raised. The data suggest that early definitive diagnosis of congenital adrenal hyperplasia can be established by measurement of plasma 17-hydroxyprogesterone.", "contents": "Early diagnosis of congenital adrenal hyperplasia by measurement of 17-hydroxyprogesterone. Plasma 17-hydroxyprogesterone was measured by a simple radioimmunoassay technique in six infants, aged 3 days to 3 months, with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hormonal levels in this group were compared to those of twenty normal newborns and to those found in sixty samples of umbilical vein blood from normal deliveries. Plasma 17-hydroxyprogesterone concentrations were markedly elevated in all congenital adrenal hyperplasia infants (range 544.7-1837 nmol/l, normal 3.03-19.06) at a time when urinary studies in some of these were either not diagnostic or inconclusive. In one infant whose cord blood was analysed, the level was also greatly raised. The data suggest that early definitive diagnosis of congenital adrenal hyperplasia can be established by measurement of plasma 17-hydroxyprogesterone."} {"id": "PMID:168999", "title": "Pathology of osteosarcoma.", "content": "Osteosarcoma of bone is a tumor composed of malignant cells that produce osteoid. Some tumors show predominant chondroid or fibromatoid ground substance. All, however, are highly malignant and about 80 per cent produce death with metastases. The roentgenogram affords important evidence for the correct diagnosis of many of them. Differential diagnosis should include consideration of those sarcomas with many benign giant cells and the group of \"telangiectatic\" osteosarcomas that may contain only small diagnostic areas. Malignant fibrous histiocytoma is now considered as a possible diagnosis for some malignant bone tumors, but the exact criteria for the diagnosis of this condition are still somewhat obscure. Newer modalities of adjunctive treatment, such as resection of pulmonary metastases, chemotherapy, and immunotherapy, give promise of improving the prognosis for osteosarcoma.", "contents": "Pathology of osteosarcoma. Osteosarcoma of bone is a tumor composed of malignant cells that produce osteoid. Some tumors show predominant chondroid or fibromatoid ground substance. All, however, are highly malignant and about 80 per cent produce death with metastases. The roentgenogram affords important evidence for the correct diagnosis of many of them. Differential diagnosis should include consideration of those sarcomas with many benign giant cells and the group of \"telangiectatic\" osteosarcomas that may contain only small diagnostic areas. Malignant fibrous histiocytoma is now considered as a possible diagnosis for some malignant bone tumors, but the exact criteria for the diagnosis of this condition are still somewhat obscure. Newer modalities of adjunctive treatment, such as resection of pulmonary metastases, chemotherapy, and immunotherapy, give promise of improving the prognosis for osteosarcoma."} {"id": "PMID:168995", "title": "Neurovascular complications following tibial osteotomy in children. A case report.", "content": "Anterior tibial sensory and motor losses following tibial osteotomy in children may result from any of 3 distinguishable etiologies. Peroneal nerve traction does not result in abnormalities of the dorsalis pedis pulse, pain on passive muscle stretch or a tense anterior tibial compartment. An anterior compartmental syndrome may or may not produce an abnormal pulse, but passive muscle stretch is painful and the compartment is tense and tender. Significant occusion of the anterior tibial artery produces diminution of the pulse and painful muscle stretch in the absence of a tense compartment. Certain pre-, intra- and postoperative measures can minimize the chance of these complications and facilitate their detection and treatment. These include: prophylactic fasciotomy, external pin fixation and frequent, thorough examination. If one of these complications arises, dressing should be loosened and the leg returned immediately to its preoperative position. Subsequent therapy is based on continued observation and the specific diagnosis.", "contents": "Neurovascular complications following tibial osteotomy in children. A case report. Anterior tibial sensory and motor losses following tibial osteotomy in children may result from any of 3 distinguishable etiologies. Peroneal nerve traction does not result in abnormalities of the dorsalis pedis pulse, pain on passive muscle stretch or a tense anterior tibial compartment. An anterior compartmental syndrome may or may not produce an abnormal pulse, but passive muscle stretch is painful and the compartment is tense and tender. Significant occusion of the anterior tibial artery produces diminution of the pulse and painful muscle stretch in the absence of a tense compartment. Certain pre-, intra- and postoperative measures can minimize the chance of these complications and facilitate their detection and treatment. These include: prophylactic fasciotomy, external pin fixation and frequent, thorough examination. If one of these complications arises, dressing should be loosened and the leg returned immediately to its preoperative position. Subsequent therapy is based on continued observation and the specific diagnosis."} {"id": "PMID:168996", "title": "Newer knowledge of non-collagenous protein in dentin and cortical bone matrix.", "content": "The current state of knowledge of the composition of the NCM components of bone and dentin has been summarized at the end of the appropriate sections. It is significant that increasing interest in the chemistry of hard tissue matrices has coincided with the development and refinement of a wide range of separation techniques, resulting in the isolation of an unexpectedly large number of components. The most sophisticated techniques, such as iso-electric focusing and isotachophoresis, give rise to discrete fractions often of very similar composition, particularly in terms of amino acid content. Such components might best be considered in groups, especially should such groups be identified in terms of common immunochemical properties. Dickson has used such an approach in a recent study of the proteins of sheep cortical bone. The Liverpool group has approached the problem on a broad front and thus directed attention to the number and diversity of NCM components, but it will be seen that those studies directed to the isolation of a specific component have invariably revealed the presence of several other fractions, set aside while attention was directed to the component under investigation. It is clear that the major proportion of bone and dentin NCM consists of glycoproteins of the less-acidic and anionic types. Several of the anionic components contain phosphate, levels being higher in those derived from dentin. Glycosaminoglycans, the first class of non-collagenous compounds to be identified in hard tissue matrices, are now known to comprise only about 5-7 per cent of the NCM. Precise details of the glycosaminoglycan fraction of human dentin and considerable information concerning that of bovine bone are now available. The major component in each tissue is chondroitin-4-sulfate, which exists in the form of proteoglycan, the protein moieties of those from bovine bone and human dentin being very different. Although greater interest is currently being shown in the glycoprotein fractions, several studies have been made of the calcium-binding properties of proteoglycan preparations and of individual glycosaminoglycans. Attempts to relate differences in chemical composition and properties to specific bone sites may not prove to be the best approach to the study of the precise chemistry of mineralization. It is clear, from the earlier work of Lindenbaum and Kuettner that mineralization takes place in a very narrow layer which will normally represent only a fraction of a typical zone prepared for analysis...", "contents": "Newer knowledge of non-collagenous protein in dentin and cortical bone matrix. The current state of knowledge of the composition of the NCM components of bone and dentin has been summarized at the end of the appropriate sections. It is significant that increasing interest in the chemistry of hard tissue matrices has coincided with the development and refinement of a wide range of separation techniques, resulting in the isolation of an unexpectedly large number of components. The most sophisticated techniques, such as iso-electric focusing and isotachophoresis, give rise to discrete fractions often of very similar composition, particularly in terms of amino acid content. Such components might best be considered in groups, especially should such groups be identified in terms of common immunochemical properties. Dickson has used such an approach in a recent study of the proteins of sheep cortical bone. The Liverpool group has approached the problem on a broad front and thus directed attention to the number and diversity of NCM components, but it will be seen that those studies directed to the isolation of a specific component have invariably revealed the presence of several other fractions, set aside while attention was directed to the component under investigation. It is clear that the major proportion of bone and dentin NCM consists of glycoproteins of the less-acidic and anionic types. Several of the anionic components contain phosphate, levels being higher in those derived from dentin. Glycosaminoglycans, the first class of non-collagenous compounds to be identified in hard tissue matrices, are now known to comprise only about 5-7 per cent of the NCM. Precise details of the glycosaminoglycan fraction of human dentin and considerable information concerning that of bovine bone are now available. The major component in each tissue is chondroitin-4-sulfate, which exists in the form of proteoglycan, the protein moieties of those from bovine bone and human dentin being very different. Although greater interest is currently being shown in the glycoprotein fractions, several studies have been made of the calcium-binding properties of proteoglycan preparations and of individual glycosaminoglycans. Attempts to relate differences in chemical composition and properties to specific bone sites may not prove to be the best approach to the study of the precise chemistry of mineralization. It is clear, from the earlier work of Lindenbaum and Kuettner that mineralization takes place in a very narrow layer which will normally represent only a fraction of a typical zone prepared for analysis..."} {"id": "PMID:169000", "title": "Electron microscopic observations of 20 human osteosarcomas.", "content": "Twenty primary osteosarcomas of bone and two osteosarcomas metastatic to the lung were examined by electron microscopy. The tumor cells, whether from an area exhibiting chondroid, osteoid or collagenous matrix, showed common abnormalities in configuration and fine structure. The cells tended to be spindle-shaped with centralized nuclei. The nucleus was enlarged, irregular in shape, and frequently lobulated. The choromatin was dense and arranged around the periphery of the nucleus. There was a large prominent, irregularly shaped nucleolus. Smooth membranes were sparse to absent. The rough endoplasmic reticulum was abundant, disorderly, and tended to be markedly dilated in mature cells. The mitochondria were numerous, variable in size and configuration, and were intimately surrounded by rough endoplasmic reticulum. The collagenous matrix was disorganized with the fibers and bundles randomly oriented and arranged. No structures definitely identifiable as virus-particles were seen. However, microstructures resembling unenveloped nucleocapsids of paramyxo- or related viruses were noted. All fine structure abnormalities could be associated with an increased metabolic rate and/or with abnormal protein and enzyme synthesis. No definitive diagnostic features were found. The fine structure of cell cultures derived from the osteosarcomas in this study was similar to that of the fresh tissue. No virus-like particles were seen in any of these cell lines.", "contents": "Electron microscopic observations of 20 human osteosarcomas. Twenty primary osteosarcomas of bone and two osteosarcomas metastatic to the lung were examined by electron microscopy. The tumor cells, whether from an area exhibiting chondroid, osteoid or collagenous matrix, showed common abnormalities in configuration and fine structure. The cells tended to be spindle-shaped with centralized nuclei. The nucleus was enlarged, irregular in shape, and frequently lobulated. The choromatin was dense and arranged around the periphery of the nucleus. There was a large prominent, irregularly shaped nucleolus. Smooth membranes were sparse to absent. The rough endoplasmic reticulum was abundant, disorderly, and tended to be markedly dilated in mature cells. The mitochondria were numerous, variable in size and configuration, and were intimately surrounded by rough endoplasmic reticulum. The collagenous matrix was disorganized with the fibers and bundles randomly oriented and arranged. No structures definitely identifiable as virus-particles were seen. However, microstructures resembling unenveloped nucleocapsids of paramyxo- or related viruses were noted. All fine structure abnormalities could be associated with an increased metabolic rate and/or with abnormal protein and enzyme synthesis. No definitive diagnostic features were found. The fine structure of cell cultures derived from the osteosarcomas in this study was similar to that of the fresh tissue. No virus-like particles were seen in any of these cell lines."} {"id": "PMID:168997", "title": "Collagenolytic systems in rheumatoid arthritis.", "content": "As the proliferative lesion of rheumatoid arthritis becomes polarized and invasion of articular cartilage and subchondral bone begins, it is likely that many mesenchymal cells, including periosteal and perichondral cells, and perhaps even the chondrocytes and osteoblasts themselves can be activated to produce destructive enzymes. Early in the course of RA cartilage proteoglycans are depleted, leaving the remaining collagen more susceptible to mechanical breakdown as well as to enzymatic breakdown. Specific collagenases are released by synovial cells and, in addition, by polymorphonuclear leukocytes. The latter enzyme may account for free collagenase found in synovial fluid, a finding possibly related to saturation of inhibitory proteins by proteases with greater affinity for them, leaving collagenase active. At this time in the course of rheumatoid arthritis, a joint would be under double jeopardy from enzymes released by the invading pannus as well as by collagenase free and active in the synovial fluid. Rapid destruction could occur. Although cartilage collagen has an intrinsic resistance to collagenase conferred by its primary structure and by higher order structure (e.g. intermolecular cross-links), it seems wise to cool down hot joints because increased temperature may increase the rate of collagen degradation and, therefore, cartilage destruction. In addition, superimposed sepsis or acute flares of rheumatoid disease result in enough influx of polymorphonuclear leukocytes into the joints to result in free collagenolytic activity being present. This provides a rationale for frequent aspiration of any joint fluid, septic or otherwise, containing high polymorphonuclear leukocyte counts.", "contents": "Collagenolytic systems in rheumatoid arthritis. As the proliferative lesion of rheumatoid arthritis becomes polarized and invasion of articular cartilage and subchondral bone begins, it is likely that many mesenchymal cells, including periosteal and perichondral cells, and perhaps even the chondrocytes and osteoblasts themselves can be activated to produce destructive enzymes. Early in the course of RA cartilage proteoglycans are depleted, leaving the remaining collagen more susceptible to mechanical breakdown as well as to enzymatic breakdown. Specific collagenases are released by synovial cells and, in addition, by polymorphonuclear leukocytes. The latter enzyme may account for free collagenase found in synovial fluid, a finding possibly related to saturation of inhibitory proteins by proteases with greater affinity for them, leaving collagenase active. At this time in the course of rheumatoid arthritis, a joint would be under double jeopardy from enzymes released by the invading pannus as well as by collagenase free and active in the synovial fluid. Rapid destruction could occur. Although cartilage collagen has an intrinsic resistance to collagenase conferred by its primary structure and by higher order structure (e.g. intermolecular cross-links), it seems wise to cool down hot joints because increased temperature may increase the rate of collagen degradation and, therefore, cartilage destruction. In addition, superimposed sepsis or acute flares of rheumatoid disease result in enough influx of polymorphonuclear leukocytes into the joints to result in free collagenolytic activity being present. This provides a rationale for frequent aspiration of any joint fluid, septic or otherwise, containing high polymorphonuclear leukocyte counts."} {"id": "PMID:169002", "title": "Studies on characterization of the integration sites of avian RNA tumor virus-specific DNA.", "content": "A sequential hybridization procedure is described which allows the integration sites of viral-specific DNA to be characterized according to their reassociation kinetics. In addition, this approach enables us to estimate the size of the integrated viral DNA. Endogenous virus sequences in normal cells appear to be associated with cell sequences reiterated 1200 times, and each integration unit is approximately equal to one 35S RNA subunit. In AMV-infected cells, the additional AMV-specific DNA sequences reassociate as if they were integrated adjacent to unique cellular DNA or in tandem with the endogenous viral DNA sequences.", "contents": "Studies on characterization of the integration sites of avian RNA tumor virus-specific DNA. A sequential hybridization procedure is described which allows the integration sites of viral-specific DNA to be characterized according to their reassociation kinetics. In addition, this approach enables us to estimate the size of the integrated viral DNA. Endogenous virus sequences in normal cells appear to be associated with cell sequences reiterated 1200 times, and each integration unit is approximately equal to one 35S RNA subunit. In AMV-infected cells, the additional AMV-specific DNA sequences reassociate as if they were integrated adjacent to unique cellular DNA or in tandem with the endogenous viral DNA sequences."} {"id": "PMID:168998", "title": "A study of skeletal age and height in girls with idiopathic scoliosis.", "content": "The height and skeletal age of girls with idiopathic scoliosis were studied. The skeletal age was evaluated by two independent methods and was compared with the chronological age and the corrected height of the patients. With both methods the same tendency was noticed. Early in the adolescence (ages 11 and 12 years) the skeletal development was more advanced in girls with idiopathic scoliosis than expected. Later (ages 16 and 17 years) the reverse condition was found. The standing height, corrected for the deformity, was significantly greater in idiopathic scoliosis patients than in controls of either the same chronological or skeletal age. These observations indicate that girls with adolescent idiopathic scoliosis have a growth pattern differing from normal, and that growth factors are connected to the disease.", "contents": "A study of skeletal age and height in girls with idiopathic scoliosis. The height and skeletal age of girls with idiopathic scoliosis were studied. The skeletal age was evaluated by two independent methods and was compared with the chronological age and the corrected height of the patients. With both methods the same tendency was noticed. Early in the adolescence (ages 11 and 12 years) the skeletal development was more advanced in girls with idiopathic scoliosis than expected. Later (ages 16 and 17 years) the reverse condition was found. The standing height, corrected for the deformity, was significantly greater in idiopathic scoliosis patients than in controls of either the same chronological or skeletal age. These observations indicate that girls with adolescent idiopathic scoliosis have a growth pattern differing from normal, and that growth factors are connected to the disease."} {"id": "PMID:169003", "title": "Infectious viral DNA in Rous sarcoma virus-transformed nonproducer and producer animal cells.", "content": "Nonproducer and producer RSV-transformed cells and producer nontransforming virus-infected cells harbor viral DNA specifying the respective avian tumor virus. In nonproducer Rous sarcoma cells, the residing viral DNA is linear, double-stranded and covalently linked to the chromosomal DNA. Both double-stranded and single-stranded forms of RSV DNA transfect chicken cells. The progeny virus is indistinguishable from the DNA parent with respect to the morphological, biological and antigenic properties. Unlike the DNA extracted from nonproducer RSV-transformed mammalian cells, that extracted from producer RSV-transformed chicken cells gives rise, in transfection experiments, to both sarcoma virus and its nontransforming derivative. The DNA from nontransforming virus-infected chicken cells generates only nontransforming viruses. The frequency of nontransforming virus recovery is different from that of sarcoma virus recovery, the latter being a nonlinear function of the amount of transfecting DNA, while the former may suggest a linear relationship. On the other hand, the end-point dilution of transfecting DNA for sarcoma virus recovery is approximately the same as that for nontransforming virus recovery. The following is assumed: Sarcoma viruses and nontransforming derivatives are recovered from two different species of viral DNA which carry or lack, respectively, the transforming genetic material. The size of double-stranded viral DNA is substantially smaller than 20 times 10(6) daltons. In transfection experiments, the sarcoma virus DNA is first integrated into the host cell genome before being expressed, while the nontransforming viral DNA apparently bypasses the integration step. The latter DNA generates the progeny virus when taken up, carried, and transcribed in a permissive cell.", "contents": "Infectious viral DNA in Rous sarcoma virus-transformed nonproducer and producer animal cells. Nonproducer and producer RSV-transformed cells and producer nontransforming virus-infected cells harbor viral DNA specifying the respective avian tumor virus. In nonproducer Rous sarcoma cells, the residing viral DNA is linear, double-stranded and covalently linked to the chromosomal DNA. Both double-stranded and single-stranded forms of RSV DNA transfect chicken cells. The progeny virus is indistinguishable from the DNA parent with respect to the morphological, biological and antigenic properties. Unlike the DNA extracted from nonproducer RSV-transformed mammalian cells, that extracted from producer RSV-transformed chicken cells gives rise, in transfection experiments, to both sarcoma virus and its nontransforming derivative. The DNA from nontransforming virus-infected chicken cells generates only nontransforming viruses. The frequency of nontransforming virus recovery is different from that of sarcoma virus recovery, the latter being a nonlinear function of the amount of transfecting DNA, while the former may suggest a linear relationship. On the other hand, the end-point dilution of transfecting DNA for sarcoma virus recovery is approximately the same as that for nontransforming virus recovery. The following is assumed: Sarcoma viruses and nontransforming derivatives are recovered from two different species of viral DNA which carry or lack, respectively, the transforming genetic material. The size of double-stranded viral DNA is substantially smaller than 20 times 10(6) daltons. In transfection experiments, the sarcoma virus DNA is first integrated into the host cell genome before being expressed, while the nontransforming viral DNA apparently bypasses the integration step. The latter DNA generates the progeny virus when taken up, carried, and transcribed in a permissive cell."} {"id": "PMID:169004", "title": "Infectious DNA from cells infected with Rous sarcoma virus, reticuloendotheliosis virus or Rous-associated virus-O.", "content": "We have described an efficient and quantitative assay for infectious DNA of the avian ribodeoxyviruses and have applied this method to study the possible existence of infectious viral DNAs in uninfected cells. Infectious DNA from cells infected with RSV or REV consisted of a single unit of DNA with a specific infectivity of 10(-5)-10(-6). The minimum molecular weight of RSV DNA required for infection of chicken cells was about 6 million, while the minimum molecular weight of infectious REV DNA was about 20 million. This difference may reflect complementation of the RSV DNA by endogenous avian leukosis virus-related DNA in uninfected chicken cells. Uninfected chicken cells do not contain infectious DNA for an REV, nor for a strongly transforming or a nontransforming avian leukosis virus.", "contents": "Infectious DNA from cells infected with Rous sarcoma virus, reticuloendotheliosis virus or Rous-associated virus-O. We have described an efficient and quantitative assay for infectious DNA of the avian ribodeoxyviruses and have applied this method to study the possible existence of infectious viral DNAs in uninfected cells. Infectious DNA from cells infected with RSV or REV consisted of a single unit of DNA with a specific infectivity of 10(-5)-10(-6). The minimum molecular weight of RSV DNA required for infection of chicken cells was about 6 million, while the minimum molecular weight of infectious REV DNA was about 20 million. This difference may reflect complementation of the RSV DNA by endogenous avian leukosis virus-related DNA in uninfected chicken cells. Uninfected chicken cells do not contain infectious DNA for an REV, nor for a strongly transforming or a nontransforming avian leukosis virus."} {"id": "PMID:169005", "title": "AMV RNA transcription in cell-free systems and properties of in vitro chromatin-directed RNA synthesis.", "content": "In this report we have presented evidence that viral sequences in the genome of AMV-infected myeloblasts can be transcribed in vitro. The RNA products synthesized in either nuclei isolated from these cells or by eukaryotic RNA polymerase B from the isolated chromatin contained approximately 1% virus-specific sequences. This result, which is in agreement with the fraction of viral RNA in infected cells (Garapin et al. 1971), is higher than expected from a random transcription of the genome, and thus shows that a degree of selectivity in transcription is maintained in both systems. The inhibition of synthesis of viral sequences in nuclei by alpha-amanitin as well as the finding that RNA polymerase B catalyzed the synthesis of viral sequences from chromatin support the hypothesis that the expression of viral information is mediated by nucleoplasmic RNA polymerase. An investigation of the properties of the chromatin-directed products led to the suggestion that RNA synthesis in vitro was initiated on single-stranded or denatured regions of the template; a limiting factor in the synthesis of large molecular weight RNA from isolated chromatin appeared to be the extent of the denatured region available to the enzyme. These findings are consistent with the suggestion that gene activation in eukaryotic organisms results from the unwinding of segments of chromatin DNA (Crick 1971).", "contents": "AMV RNA transcription in cell-free systems and properties of in vitro chromatin-directed RNA synthesis. In this report we have presented evidence that viral sequences in the genome of AMV-infected myeloblasts can be transcribed in vitro. The RNA products synthesized in either nuclei isolated from these cells or by eukaryotic RNA polymerase B from the isolated chromatin contained approximately 1% virus-specific sequences. This result, which is in agreement with the fraction of viral RNA in infected cells (Garapin et al. 1971), is higher than expected from a random transcription of the genome, and thus shows that a degree of selectivity in transcription is maintained in both systems. The inhibition of synthesis of viral sequences in nuclei by alpha-amanitin as well as the finding that RNA polymerase B catalyzed the synthesis of viral sequences from chromatin support the hypothesis that the expression of viral information is mediated by nucleoplasmic RNA polymerase. An investigation of the properties of the chromatin-directed products led to the suggestion that RNA synthesis in vitro was initiated on single-stranded or denatured regions of the template; a limiting factor in the synthesis of large molecular weight RNA from isolated chromatin appeared to be the extent of the denatured region available to the enzyme. These findings are consistent with the suggestion that gene activation in eukaryotic organisms results from the unwinding of segments of chromatin DNA (Crick 1971)."} {"id": "PMID:169010", "title": "Qualitative and quantitative studies of AKR-type murine leukemia virus sequences in mouse DNA.", "content": "Utilizing a single-stranded [3H]DNA probe highly representative of AKR viral 70S RNA, we have performed association kinetics experiments with cellular DNA in vast excess from 3 high-, 5 low- and 4 non-virus-yielding mouse strains. Our hybridization studies indicate that in the strains so far tested, the complete genome of the AKR-type MLV is present in the DNA of the embryos of both high- and low-virus-yielding mouse strains, while DNA of non-virus strains contains only a part of the genome. Furthermore, at least two populations of virus-specific DNA sequences can be identified (more abundant and less abundant species) according to their rate of association. Low-virus-yielding mouse strains contain a smaller number (1-2 copies) of the less abundant species, and thus a lower number of complete viral genome than do high-virus strains (3-4 copies). Non-virus-yielding strains are lacking these less abundant sequences in their genome. DNA from wild Mus musculus also contained viral sequences, the sample tested showing association kinetics identical to the non-virus-producing strains. Thus there is a good correlation between completeness of the AKR-type MLV genome in cellular DNA and the capacity of the cells to release AKR-type MLV. Mice of a non-virus-yielding strain made partially congenic for the AKR virus-inducing locus Akv-1 contained the complete virus genome, confirming that this locus consists of structural genes of the virus.", "contents": "Qualitative and quantitative studies of AKR-type murine leukemia virus sequences in mouse DNA. Utilizing a single-stranded [3H]DNA probe highly representative of AKR viral 70S RNA, we have performed association kinetics experiments with cellular DNA in vast excess from 3 high-, 5 low- and 4 non-virus-yielding mouse strains. Our hybridization studies indicate that in the strains so far tested, the complete genome of the AKR-type MLV is present in the DNA of the embryos of both high- and low-virus-yielding mouse strains, while DNA of non-virus strains contains only a part of the genome. Furthermore, at least two populations of virus-specific DNA sequences can be identified (more abundant and less abundant species) according to their rate of association. Low-virus-yielding mouse strains contain a smaller number (1-2 copies) of the less abundant species, and thus a lower number of complete viral genome than do high-virus strains (3-4 copies). Non-virus-yielding strains are lacking these less abundant sequences in their genome. DNA from wild Mus musculus also contained viral sequences, the sample tested showing association kinetics identical to the non-virus-producing strains. Thus there is a good correlation between completeness of the AKR-type MLV genome in cellular DNA and the capacity of the cells to release AKR-type MLV. Mice of a non-virus-yielding strain made partially congenic for the AKR virus-inducing locus Akv-1 contained the complete virus genome, confirming that this locus consists of structural genes of the virus."} {"id": "PMID:169028", "title": "Viral gene functions expressed and detected by temperature-sensitive mutants of herpes simplex virus.", "content": "The expression of HSV-specific gene functions by 22 ts mutants of HSV-1 in 15 complementation groups and 8 ts mutants of HSV-2 in 7 complementation groups has been studied at the nonpermissive temperature. Four cistrons of HSV-1 and three cistrons of HSV-2 with defects in viral DNA and DAN polymerase synthesis were identified. DNA-mutants of HSV-1 revealed a greater alteration in HSV polypeptide synthesis and viral assembly than DNA- mutants of HSV-2. Mutants with apparent defects in structural proteins have been identified for both HSV-1 and HSV-2 as demonstrated by their increased themolability. The general organization of the provisional HSV-1 and HSV-2 linkage maps revealed a similarity in the arrangement of functionally related cistrons, with DNA- mutants being located on the left-hand side of each map and mutants with phenotypic properties similar to those of the wild-type virus, on the right-hand side. An early polypeptide of HSV (VP175, MW 175,000) was found to accumulate in cells infected at the nonpermissive temperature withts mutants of HSV-1 in complementation group B. The VP175 polypeptide was isolated from such cells by a combination of SDS-preparative and analytical disc gel electrophoresis. Antiserum prepared to this polypeptide was found to descriminate between HSV-1 and HSV-2 by immunofluorescence. On the other hand, type-specific gene functions of HSV-1 and HSV-2 were not demonstrated through intertypic complementation and recombination tests with heterologous mutant pairs, whereas mutually exchangeable or common gene functions were readily identified. Eight ts mutants of HSV-2 were used to detect functional HSV genes in hamster embryo cells transformed by HSV-2. Normal hamster cells and SV40-transformed hamster cells failed to support the replication of the mutants at the nonpermissive temperature. However, the replication of two mutants, defective in late functions, was significantly enhanced in two independently derived HSV-2-transformed cell lines. Thus functional HSV genetic information was detected in HSV-2-transformed cells through the use of ts mutants. Moreover, it appears that the information present in both cell lines is not only specific but involves late HSV functions.", "contents": "Viral gene functions expressed and detected by temperature-sensitive mutants of herpes simplex virus. The expression of HSV-specific gene functions by 22 ts mutants of HSV-1 in 15 complementation groups and 8 ts mutants of HSV-2 in 7 complementation groups has been studied at the nonpermissive temperature. Four cistrons of HSV-1 and three cistrons of HSV-2 with defects in viral DNA and DAN polymerase synthesis were identified. DNA-mutants of HSV-1 revealed a greater alteration in HSV polypeptide synthesis and viral assembly than DNA- mutants of HSV-2. Mutants with apparent defects in structural proteins have been identified for both HSV-1 and HSV-2 as demonstrated by their increased themolability. The general organization of the provisional HSV-1 and HSV-2 linkage maps revealed a similarity in the arrangement of functionally related cistrons, with DNA- mutants being located on the left-hand side of each map and mutants with phenotypic properties similar to those of the wild-type virus, on the right-hand side. An early polypeptide of HSV (VP175, MW 175,000) was found to accumulate in cells infected at the nonpermissive temperature withts mutants of HSV-1 in complementation group B. The VP175 polypeptide was isolated from such cells by a combination of SDS-preparative and analytical disc gel electrophoresis. Antiserum prepared to this polypeptide was found to descriminate between HSV-1 and HSV-2 by immunofluorescence. On the other hand, type-specific gene functions of HSV-1 and HSV-2 were not demonstrated through intertypic complementation and recombination tests with heterologous mutant pairs, whereas mutually exchangeable or common gene functions were readily identified. Eight ts mutants of HSV-2 were used to detect functional HSV genes in hamster embryo cells transformed by HSV-2. Normal hamster cells and SV40-transformed hamster cells failed to support the replication of the mutants at the nonpermissive temperature. However, the replication of two mutants, defective in late functions, was significantly enhanced in two independently derived HSV-2-transformed cell lines. Thus functional HSV genetic information was detected in HSV-2-transformed cells through the use of ts mutants. Moreover, it appears that the information present in both cell lines is not only specific but involves late HSV functions."} {"id": "PMID:169030", "title": "Transformation of cells by herpes simplex virus--fact or fantasy?", "content": "The replication of herpes simplex virus types 1 and 2 is defective in XC cells. One lesion is the failure of viral proteins to be transported to the cell nucleus. The resistance of XC cells to the toxic effects of herpes simplex virus is apparently not due directly to the presence of RNA tumor virus in these cells. Other cell lines transformed by RNA tumor viruses exhibited no comparable resistance. The nature of the association between HSV and cell for a number of generations after first selecting \"transformants\" is not yet established; on prolonged subculture, much of the original HSV information fails to be expressed. Not more than approximately to 0.1 viral genomes per cell remains permanently associated with the host DNA. The \"transformants\" retain the capacity to synthesize HSV-specific polypeptides, as determined by radioimmunoprecipitation. The \"transformants\" have a number of characteristics which distinguish them from parental cells, and such characteristics in the light of the immunological data suggest that XC cells exposed to HSV can permanently retain HSV-specific information.", "contents": "Transformation of cells by herpes simplex virus--fact or fantasy? The replication of herpes simplex virus types 1 and 2 is defective in XC cells. One lesion is the failure of viral proteins to be transported to the cell nucleus. The resistance of XC cells to the toxic effects of herpes simplex virus is apparently not due directly to the presence of RNA tumor virus in these cells. Other cell lines transformed by RNA tumor viruses exhibited no comparable resistance. The nature of the association between HSV and cell for a number of generations after first selecting \"transformants\" is not yet established; on prolonged subculture, much of the original HSV information fails to be expressed. Not more than approximately to 0.1 viral genomes per cell remains permanently associated with the host DNA. The \"transformants\" retain the capacity to synthesize HSV-specific polypeptides, as determined by radioimmunoprecipitation. The \"transformants\" have a number of characteristics which distinguish them from parental cells, and such characteristics in the light of the immunological data suggest that XC cells exposed to HSV can permanently retain HSV-specific information."} {"id": "PMID:169034", "title": "Plasmid DNA as a possible state of Epstein-Barr virus genomes in nonproductive cells.", "content": "It has been shown that the EBV DNA in Raji cells is located in chromosomes and that most of this EBV DNA can be separated from high molecular weight cell DNA both in alkaline and neutral glycerol gradients. The data indicate that the latent EBV DNA may exist possibly as a plasmid DNA. As 50 genomes of EBV DNA are equal to 0.1% of the total cell DNA, it may be quite conceivable that such an amount of DNA should remain in a non-integrated form. Chromosomal location may be a requisite for any DNA to persist in the nucleus of cells and to be divided into daughter cells evenly. As the present studies measured only the status of the major portion of EBV genomes in Raji cells, a possibility still remains that a few genomes of EBV may be linearly integrated into cell DNA and these may be responsible for cellular transformation. Another possibility that a small piece of cellular DNA might be attached to EBV DNA in Raji cells, which might serve as a control signal for replication and/or transcription of the latent virust DNA, has also not been ruled out. Even though EBV DNA is not integrated covalently into cell DNA, the association of the virus genomes with cells is very stable and the number of EBV genomes remains unchanged throughout many cell generations. In synchronized cells, all EBV genomes replicate simultaneously at an early S phase before maximum synthesis of cell DNA replication occurs (Hamper et al. 1974). This indicates that EBV DNA in a plasmid state is strictly under a cellular control mechanism. How this latent virus DNA is controlled in cells will be examined in future studies.", "contents": "Plasmid DNA as a possible state of Epstein-Barr virus genomes in nonproductive cells. It has been shown that the EBV DNA in Raji cells is located in chromosomes and that most of this EBV DNA can be separated from high molecular weight cell DNA both in alkaline and neutral glycerol gradients. The data indicate that the latent EBV DNA may exist possibly as a plasmid DNA. As 50 genomes of EBV DNA are equal to 0.1% of the total cell DNA, it may be quite conceivable that such an amount of DNA should remain in a non-integrated form. Chromosomal location may be a requisite for any DNA to persist in the nucleus of cells and to be divided into daughter cells evenly. As the present studies measured only the status of the major portion of EBV genomes in Raji cells, a possibility still remains that a few genomes of EBV may be linearly integrated into cell DNA and these may be responsible for cellular transformation. Another possibility that a small piece of cellular DNA might be attached to EBV DNA in Raji cells, which might serve as a control signal for replication and/or transcription of the latent virust DNA, has also not been ruled out. Even though EBV DNA is not integrated covalently into cell DNA, the association of the virus genomes with cells is very stable and the number of EBV genomes remains unchanged throughout many cell generations. In synchronized cells, all EBV genomes replicate simultaneously at an early S phase before maximum synthesis of cell DNA replication occurs (Hamper et al. 1974). This indicates that EBV DNA in a plasmid state is strictly under a cellular control mechanism. How this latent virus DNA is controlled in cells will be examined in future studies."} {"id": "PMID:169040", "title": "35S a and b RNA subunits of avian RNA tumor virus strains cloned and passaged in chick and duck cells.", "content": "The RNA of transforming and nontransforming avian RNA tumor viruses was heat denatured and examined for its 35S subunit composition by polyacrylamide gel electrophoresis (gel slicing and/or autoradiography). The RNA of virus strains capable of transforming chick embryo fibroblasts in vitro always contained a subunits: the RNA of Pr-RSV of subgroups A, B or C was composed only of a subunits, even after prolonged passage in chick cells, whereas the RNA of SR-RSV-A, SR-RSV-B, SR-RSV-D(H) and B77 also contained b subunits in varying amounts, even when examined as early as possible (8-10 days) after cloning. The b subunit content did not correlate with length of time after cloning. Nontransforming viruses such as RAV-2 and nontransforming derivatives of transforming viruses such as NT-SR-RSV-A, SR-RSV-B AV-3, NC-SRV-D(H), NC-SRV-D(H)(U4), NC-B77-42 and NC-B77-43 contained only b subunits. When B77 virus grown in chick cells was passaged in duck embryo fibroblasts, the ratio of a/b subunits in its RNA did not change markedly. However, when it was cloned in duck embryo fibroblasts, the transformed clones produced virus that contained almost exclusively b subunits. On transfer to chick cells, a subunits once again appeared, and the a/b subunit ratio was soon similar to that of the original B77. B77 virus produced by cloned, transformed duck embryo fibroblasts was found to contain a large excess of nontransforming virus particles.", "contents": "35S a and b RNA subunits of avian RNA tumor virus strains cloned and passaged in chick and duck cells. The RNA of transforming and nontransforming avian RNA tumor viruses was heat denatured and examined for its 35S subunit composition by polyacrylamide gel electrophoresis (gel slicing and/or autoradiography). The RNA of virus strains capable of transforming chick embryo fibroblasts in vitro always contained a subunits: the RNA of Pr-RSV of subgroups A, B or C was composed only of a subunits, even after prolonged passage in chick cells, whereas the RNA of SR-RSV-A, SR-RSV-B, SR-RSV-D(H) and B77 also contained b subunits in varying amounts, even when examined as early as possible (8-10 days) after cloning. The b subunit content did not correlate with length of time after cloning. Nontransforming viruses such as RAV-2 and nontransforming derivatives of transforming viruses such as NT-SR-RSV-A, SR-RSV-B AV-3, NC-SRV-D(H), NC-SRV-D(H)(U4), NC-B77-42 and NC-B77-43 contained only b subunits. When B77 virus grown in chick cells was passaged in duck embryo fibroblasts, the ratio of a/b subunits in its RNA did not change markedly. However, when it was cloned in duck embryo fibroblasts, the transformed clones produced virus that contained almost exclusively b subunits. On transfer to chick cells, a subunits once again appeared, and the a/b subunit ratio was soon similar to that of the original B77. B77 virus produced by cloned, transformed duck embryo fibroblasts was found to contain a large excess of nontransforming virus particles."} {"id": "PMID:169043", "title": "A biochemical and genetic analysis of mammalian RNA-containing sarcoma viruses.", "content": "Current studies have shown that all mammalian sarcoma-producing viruses, whether isolated from laboratory experiments of naturally occurring tumors, are deletion mutants of replicating mammalian type C viruses. Nonproducer cells transformed by any of these sarcoma viruses contain RNA homologous to mammalian leukemia viruses, even though the cells contain no known proteins currently coded for by the mammalian leukemia virus. This mammalian leukemia virus information (FT-) is a genetically stable part of the mammalian sarcoma viruses (FT+). Second, another component in the Kirsten and Harvey sarcoma viruses can be identified in addition to this leukemia virus information for the homologous leukemia virus; at least part of the additional information came from rat type C viruses from the animals in which the sarcoma viruses were isolated. This indicates that these two mammalian sarcoma viruses are recombinants between mouse leukemia virus and genetic information in rat cells and suggests that the process of formation of the sarcoma virus is analogous to transduction of information in bacteriophage. Third, the Kirsten sarcoma virus seems to have a third component in it separate from either the mouse leukemia virus or rat leukemia virus information. Fourth, and FT+ leukemia virus isolated from mice, the Abelson leukemia virus which causes as B-cell leukemia, is also defective and can be shown to have information homologous to Moloney leukemia virus. Fifth, in the feline sarcoma virus, feline leukemia information can be detected, but information for the other cat virus, RD-114, cannot be detected. Finally, mutants of Kirsten sarcoma virus temperature sensitive for the maintenance of transformation have been isolated, and out of ten such mutants, thus far no complementation has been observed.", "contents": "A biochemical and genetic analysis of mammalian RNA-containing sarcoma viruses. Current studies have shown that all mammalian sarcoma-producing viruses, whether isolated from laboratory experiments of naturally occurring tumors, are deletion mutants of replicating mammalian type C viruses. Nonproducer cells transformed by any of these sarcoma viruses contain RNA homologous to mammalian leukemia viruses, even though the cells contain no known proteins currently coded for by the mammalian leukemia virus. This mammalian leukemia virus information (FT-) is a genetically stable part of the mammalian sarcoma viruses (FT+). Second, another component in the Kirsten and Harvey sarcoma viruses can be identified in addition to this leukemia virus information for the homologous leukemia virus; at least part of the additional information came from rat type C viruses from the animals in which the sarcoma viruses were isolated. This indicates that these two mammalian sarcoma viruses are recombinants between mouse leukemia virus and genetic information in rat cells and suggests that the process of formation of the sarcoma virus is analogous to transduction of information in bacteriophage. Third, the Kirsten sarcoma virus seems to have a third component in it separate from either the mouse leukemia virus or rat leukemia virus information. Fourth, and FT+ leukemia virus isolated from mice, the Abelson leukemia virus which causes as B-cell leukemia, is also defective and can be shown to have information homologous to Moloney leukemia virus. Fifth, in the feline sarcoma virus, feline leukemia information can be detected, but information for the other cat virus, RD-114, cannot be detected. Finally, mutants of Kirsten sarcoma virus temperature sensitive for the maintenance of transformation have been isolated, and out of ten such mutants, thus far no complementation has been observed."} {"id": "PMID:169044", "title": "Genetic recombination among temperature-sensitive mutnats of Rous sarcoma virus.", "content": "Genetic recombination of RSV has been studied, using ts mutations in both initiation and maintenance of transformation as markers. The progeny of a single cycle of mixed infection appears to contain no recombinants, but yields heterozygous particles or viral clumps. On subsequent cycles of infection some of these heterozygotes/clumps persist, but they also segregate recombinant viruses. Some of the markers in these recombinants show evidence of linkage and thus probably recombine by intramolecular exchanges. Studies of td ts mutants (the class most frequently isolated from stock virus) show that recombination between them occurs at a level sufficient to explain cooperative transformation by these viruses. Furthermors, this genetic recombination is probably a necessary prerequisite for cooperative transformation since complementation between the mutants is absent or inefficient. The simplest explanation for this apparent lack of complementation is that the td ts mutants are all derived by lesions in the same cistron.", "contents": "Genetic recombination among temperature-sensitive mutnats of Rous sarcoma virus. Genetic recombination of RSV has been studied, using ts mutations in both initiation and maintenance of transformation as markers. The progeny of a single cycle of mixed infection appears to contain no recombinants, but yields heterozygous particles or viral clumps. On subsequent cycles of infection some of these heterozygotes/clumps persist, but they also segregate recombinant viruses. Some of the markers in these recombinants show evidence of linkage and thus probably recombine by intramolecular exchanges. Studies of td ts mutants (the class most frequently isolated from stock virus) show that recombination between them occurs at a level sufficient to explain cooperative transformation by these viruses. Furthermors, this genetic recombination is probably a necessary prerequisite for cooperative transformation since complementation between the mutants is absent or inefficient. The simplest explanation for this apparent lack of complementation is that the td ts mutants are all derived by lesions in the same cistron."} {"id": "PMID:169052", "title": "Formation of reiterated simian virus 40 DNA.", "content": "We have described studies on the biological fate of a minicircular DNA molecule that is a specific, complex deletion mutant of SV40. When the minicircular DNA alone was used to infect monkey cells, its replication was not detected. However, after infection with the minicircles and SV40 DNA together, incorporation of (3H)thymidine into both species of viral DNA was demonstrated. This finding suggests that circular, duplex viral DNA segments, much smaller than SV40 DNA, are able to be replicated in vivo. Furthermore, 26% of the (3H)thymidine-labeled, superhelical DNA sedimented more rapidly than SV40 DNA I (21S) in neutral sucrose gradients (22S-32S). A similar amount of this rapidly sedimenting DNA was also detected when intact DAR DNA containing the triplication mutant was tested. Cleavage of the purified, rapidly sedimenting DNA with R.EcoRI produced 10.4S segments (one-third the size of unit-length SV40) in addition to full-length linears (14.5S) and a new cleavage product (16.7S). Cleavage of the 21S DNA I molecules also produced 10.4S DNA. These results indicate that the minicircular molecules are amplified in vivo, yielding not only the original triplication mutant but also a heterogeneous population of oligomers in which the 10.4S segment has been reiterated as many as 6 to 9 times. Our studies support the model proposed by Khoury et al. (1974) for the generation of the original DAR triplication mutant. In our experiments, cells were infected with a minicircular DNA molecule formed in vitro, which then served as a precursor in vivo in the formation of trimers and higher oligomers, as predicted by the proposed model. The DAR triplication mutant first appeared after the third passage in primary monkey kidney cells and rapidly became the predominant species in later passages (Fareed et al. 1974)...", "contents": "Formation of reiterated simian virus 40 DNA. We have described studies on the biological fate of a minicircular DNA molecule that is a specific, complex deletion mutant of SV40. When the minicircular DNA alone was used to infect monkey cells, its replication was not detected. However, after infection with the minicircles and SV40 DNA together, incorporation of (3H)thymidine into both species of viral DNA was demonstrated. This finding suggests that circular, duplex viral DNA segments, much smaller than SV40 DNA, are able to be replicated in vivo. Furthermore, 26% of the (3H)thymidine-labeled, superhelical DNA sedimented more rapidly than SV40 DNA I (21S) in neutral sucrose gradients (22S-32S). A similar amount of this rapidly sedimenting DNA was also detected when intact DAR DNA containing the triplication mutant was tested. Cleavage of the purified, rapidly sedimenting DNA with R.EcoRI produced 10.4S segments (one-third the size of unit-length SV40) in addition to full-length linears (14.5S) and a new cleavage product (16.7S). Cleavage of the 21S DNA I molecules also produced 10.4S DNA. These results indicate that the minicircular molecules are amplified in vivo, yielding not only the original triplication mutant but also a heterogeneous population of oligomers in which the 10.4S segment has been reiterated as many as 6 to 9 times. Our studies support the model proposed by Khoury et al. (1974) for the generation of the original DAR triplication mutant. In our experiments, cells were infected with a minicircular DNA molecule formed in vitro, which then served as a precursor in vivo in the formation of trimers and higher oligomers, as predicted by the proposed model. The DAR triplication mutant first appeared after the third passage in primary monkey kidney cells and rapidly became the predominant species in later passages (Fareed et al. 1974)..."} {"id": "PMID:169060", "title": "Stepwise relaxation of supercoiled SV40 DNA.", "content": "We have shown in this paper that agarose gel electrophoresis can be used to examine the tertiary structure of supercoiled SV40 DNA. Differences as small as one superhelical turn can be detected by this method. When used as an assay, it enabled us to purify from human tissue culture cells a protein which acts on supercoiled DNA, leading to a gradual removal of its superhelical turns. Using in turn the purified DNA relaxing protein to generate reaction intermediates of DNAs with different numbers of superhelical turns, we deduced that native SV40 DNA contains a minimum of 20 physical superhelical turns. The upper limit of this number is less accurately defined, but we think that it is not higher than 24. These numbers agree within very close limits with the numbers determined previously by various indirect physical methods.", "contents": "Stepwise relaxation of supercoiled SV40 DNA. We have shown in this paper that agarose gel electrophoresis can be used to examine the tertiary structure of supercoiled SV40 DNA. Differences as small as one superhelical turn can be detected by this method. When used as an assay, it enabled us to purify from human tissue culture cells a protein which acts on supercoiled DNA, leading to a gradual removal of its superhelical turns. Using in turn the purified DNA relaxing protein to generate reaction intermediates of DNAs with different numbers of superhelical turns, we deduced that native SV40 DNA contains a minimum of 20 physical superhelical turns. The upper limit of this number is less accurately defined, but we think that it is not higher than 24. These numbers agree within very close limits with the numbers determined previously by various indirect physical methods."} {"id": "PMID:169066", "title": "Transformation of primate and rodent cells by temperature-sensitive mutants of SV40.", "content": "Cells of mouse, hamster, human and monkey origin were transformed by wild-type SV40 and by temperature-sensitive mutants defective in gene A. The mutant-transformed cells appear to be temperature sensitive for maintenance of transformation. Evidence of reversion of the transformed phenotype of nonpermissive temperatures was obtained in experiments which assayed saturation density, colony formation, and uptake of 2-deoxy-D-glucose. In addition, S antigen modulated in shift experiments while T antigen did not. Based on these results, a model is presented for the mechanism of transformation by SV40.", "contents": "Transformation of primate and rodent cells by temperature-sensitive mutants of SV40. Cells of mouse, hamster, human and monkey origin were transformed by wild-type SV40 and by temperature-sensitive mutants defective in gene A. The mutant-transformed cells appear to be temperature sensitive for maintenance of transformation. Evidence of reversion of the transformed phenotype of nonpermissive temperatures was obtained in experiments which assayed saturation density, colony formation, and uptake of 2-deoxy-D-glucose. In addition, S antigen modulated in shift experiments while T antigen did not. Based on these results, a model is presented for the mechanism of transformation by SV40."} {"id": "PMID:169069", "title": "SV40: T antigen, the A function and transformation.", "content": "T antigen, a protein found in the nuclei of SV40-transformed and -infected cells, can be purified and characterized. Our data suggest that T antigen in transformed cells is found at least in part in a large 22S complex, suggesting that this 22S form may contain T antigen complexed with other viral or host proteins. We prefer the assumption that T antigen is correlated with the A function, although a definitive in vitro proof for this hypothesis is still missing. Mutants in the A function most likely interfere with the maintenance of transformation, a result inviting the interpretation that the A function may indeed govern DNA synthesis of the transformed cell or influence the cell's ability to pass from G1 (or G0) to S. Thus transformation by SV40 may be a direct consequence of the introduction of the SV40 replicon and the presence of its initiator function which is used by the transformed cell.", "contents": "SV40: T antigen, the A function and transformation. T antigen, a protein found in the nuclei of SV40-transformed and -infected cells, can be purified and characterized. Our data suggest that T antigen in transformed cells is found at least in part in a large 22S complex, suggesting that this 22S form may contain T antigen complexed with other viral or host proteins. We prefer the assumption that T antigen is correlated with the A function, although a definitive in vitro proof for this hypothesis is still missing. Mutants in the A function most likely interfere with the maintenance of transformation, a result inviting the interpretation that the A function may indeed govern DNA synthesis of the transformed cell or influence the cell's ability to pass from G1 (or G0) to S. Thus transformation by SV40 may be a direct consequence of the introduction of the SV40 replicon and the presence of its initiator function which is used by the transformed cell."} {"id": "PMID:169073", "title": "Cytosine arabinoside- and interferon-mediated control of polyoma and SV40 genome expression.", "content": "By metabolic DNA inhibitors such as araC, viral as well as host DNA replication is suppressed in polyoma- and SV40-infected cells. The interruption of the current viral DNA replication has no effect on the current transcription of the late viral genes. The persistence of the late transcription indicates that the onset, but not the persistence, of the viral DNA replication is a prerequisite for the persistence of the late polyoma and SV40 genome transcription. Pretreatment of monkey kidney cells with poly(I):-poly(C) nearly completely inhibits the SV40 T antigen formation; the early SV40 RNA formation is suppressed far less. This type of SV40 genome control favors the concept of a primary action of poly(I):poly(C)-mediated interference on SV40 translation.", "contents": "Cytosine arabinoside- and interferon-mediated control of polyoma and SV40 genome expression. By metabolic DNA inhibitors such as araC, viral as well as host DNA replication is suppressed in polyoma- and SV40-infected cells. The interruption of the current viral DNA replication has no effect on the current transcription of the late viral genes. The persistence of the late transcription indicates that the onset, but not the persistence, of the viral DNA replication is a prerequisite for the persistence of the late polyoma and SV40 genome transcription. Pretreatment of monkey kidney cells with poly(I):-poly(C) nearly completely inhibits the SV40 T antigen formation; the early SV40 RNA formation is suppressed far less. This type of SV40 genome control favors the concept of a primary action of poly(I):poly(C)-mediated interference on SV40 translation."} {"id": "PMID:169077", "title": "Genetics of cell transformation by simian virus 40.", "content": "The results described in this paper indicate that the integration of the SV40 genome into human chromosome 7 results in the transformation of the human cells and in the expression of SV40-induced antigens. If integration of the SV40 genome in human chromosomes other than 7 ever occurs, it does not result in cell transformation and the expression of the virus-induced antigens. The expression of the SV40 T antigen in different monkey cells transformed by an adeno 7-SV40 hybrid is also related to a specific monkey chromosome. Somatic cell hybrids between normal nondividing mouse cells and SV40-transformed human cells behave as transformed cells and contain, without exception, the human chromosome 7 carrying the SV40 genome. Since no segregation into SV40 T antigen-negative hybrid clones was observed in these hybrids, it is inferred that the presence of the human chromosome 7 carrying the SV40 genome in the hybrids is mandatory for cell division.", "contents": "Genetics of cell transformation by simian virus 40. The results described in this paper indicate that the integration of the SV40 genome into human chromosome 7 results in the transformation of the human cells and in the expression of SV40-induced antigens. If integration of the SV40 genome in human chromosomes other than 7 ever occurs, it does not result in cell transformation and the expression of the virus-induced antigens. The expression of the SV40 T antigen in different monkey cells transformed by an adeno 7-SV40 hybrid is also related to a specific monkey chromosome. Somatic cell hybrids between normal nondividing mouse cells and SV40-transformed human cells behave as transformed cells and contain, without exception, the human chromosome 7 carrying the SV40 genome. Since no segregation into SV40 T antigen-negative hybrid clones was observed in these hybrids, it is inferred that the presence of the human chromosome 7 carrying the SV40 genome in the hybrids is mandatory for cell division."} {"id": "PMID:169083", "title": "Infection of mouse blastocysts with SV40 DNA: normal development of the infected embryos and persistence of SV40-specific DNA sequences in the adult animals.", "content": "In SV40-transformed culture cells, viral-specific sequences have been found to be covalently linked to host sequences (Sambrook et al. 1968). The most appealing interpretation to explain the presence of SV40-specific sequences in adult mice following infection at the preimplantation stage would be to assume that the viral DNA was integrated at this early stage of development into the host genome and was thus conserved during further development. However, our results do not exclude an extrachromosomal existence of the SV40 genome, for example, as an independently replicating plasmid or as a lytic infection in a few permissive cells. So far our attempts to demonstrate autonomous SV40 DNA replication in early mouse embryos have been unsuccessful. We plan to investigate whether the SV40-specific information can be genetically transmitted from the infected mice to their offspring; chromosomal integration would be proven if transmission of SV40 DNA occurred in accordance with simple Mendelian expectations. The injection of mouse blastocysts with purified SV40 DNA did not detectably interfere with normal development of the embryos to healthy adult mice, which were still tumor-free at one year of age. This was not due to the trivial possibility that the viral DNA did not successfully infect and was eliminated from the injected embryos, as virus-specific DNA sequences were detected in 40% of the infected year-old animals, or in about 25% of DNA preparations extracted from some of their tissues (Table 1). It is nevertheless possible that the animals may not have been old enough to exhibit tumorigenesis of SV40 origin; to test this possibility, the experiment will have to be repeated for longer survival periods. The absence of any obvious signs of expression of viral genetic functions, i.e., tumor formation, up to one year of age of the host is reminiscent of the \"cryptic transformants\" described earlier (Smith et al. 1972) which harbor SV40 information but behave essentially like normal untransformed cells. Whether transcription or translation of the virus gene can occur in infected mice is presently an open question. Testing for expression of an integrated viral genome in diverse differentiated tissues may provide a useful model system to study the regulation of differentiation. These matters are currently being investigated.", "contents": "Infection of mouse blastocysts with SV40 DNA: normal development of the infected embryos and persistence of SV40-specific DNA sequences in the adult animals. In SV40-transformed culture cells, viral-specific sequences have been found to be covalently linked to host sequences (Sambrook et al. 1968). The most appealing interpretation to explain the presence of SV40-specific sequences in adult mice following infection at the preimplantation stage would be to assume that the viral DNA was integrated at this early stage of development into the host genome and was thus conserved during further development. However, our results do not exclude an extrachromosomal existence of the SV40 genome, for example, as an independently replicating plasmid or as a lytic infection in a few permissive cells. So far our attempts to demonstrate autonomous SV40 DNA replication in early mouse embryos have been unsuccessful. We plan to investigate whether the SV40-specific information can be genetically transmitted from the infected mice to their offspring; chromosomal integration would be proven if transmission of SV40 DNA occurred in accordance with simple Mendelian expectations. The injection of mouse blastocysts with purified SV40 DNA did not detectably interfere with normal development of the embryos to healthy adult mice, which were still tumor-free at one year of age. This was not due to the trivial possibility that the viral DNA did not successfully infect and was eliminated from the injected embryos, as virus-specific DNA sequences were detected in 40% of the infected year-old animals, or in about 25% of DNA preparations extracted from some of their tissues (Table 1). It is nevertheless possible that the animals may not have been old enough to exhibit tumorigenesis of SV40 origin; to test this possibility, the experiment will have to be repeated for longer survival periods. The absence of any obvious signs of expression of viral genetic functions, i.e., tumor formation, up to one year of age of the host is reminiscent of the \"cryptic transformants\" described earlier (Smith et al. 1972) which harbor SV40 information but behave essentially like normal untransformed cells. Whether transcription or translation of the virus gene can occur in infected mice is presently an open question. Testing for expression of an integrated viral genome in diverse differentiated tissues may provide a useful model system to study the regulation of differentiation. These matters are currently being investigated."} {"id": "PMID:169097", "title": "Studies of hamster cells transformed by adenovirus 2 and the nondefective Ad2-SV40 hybrids.", "content": "Adenovirus 2 does not produce tumors when injected into newborn hamsters, and this failure is not corrected by the acquisition of the portion of the SV40 genome present in any of the nondefective Ad2-SV40 hybrid viruses. However, nonhybrid Ad2 will transform hamster cells in vitro, and these transformed cells will produce tumors when injected into newborn hamsters. This finding, taken in conjunction with other studies (Graham et al., this volume; McAllister et al., 1969; McDougall et al., this volume; Williams 1973), suggests that the categorization of Ad2 and Ad5 as \"nononcogenic\" viruses is a reflection of host response rather than an intrinsic property of the viruses. However, transformation of hamster cells by Ad2 is inefficient, requiring 10(7)-10(8) PFU to produce a focus of transformed cells. Transformation of hamster kidney cells by the nondefective hybrids cannot be associated with portions of the SV40 genome. During the transformation process, complex interactions must occur between the hamster cell genome and the viral genome of Ad2 or the nondefective hybrids. Thus while it appears that there is very little Ad2 DNA in one nonhybrid Ad2-transformed cell line, there is a larger amount of Ad2 DNA in all of the hybrid virus-transformed cell lines. Moreover, while one Ad2+ND2-transformed line has apparently lost the SV40 portion of the viral genome, it is present and transcribed in another line transformed by the same virus. Finally, in the lines of nondefective hybrid-transformed cells examined thus far, there is extensive transcription from the Ad2 H strand. This pattern of transcription differs from transcription of the viral genome in most hybrid Ad2-transformed hamster and rat cells in which L-strand transcripion predominates.", "contents": "Studies of hamster cells transformed by adenovirus 2 and the nondefective Ad2-SV40 hybrids. Adenovirus 2 does not produce tumors when injected into newborn hamsters, and this failure is not corrected by the acquisition of the portion of the SV40 genome present in any of the nondefective Ad2-SV40 hybrid viruses. However, nonhybrid Ad2 will transform hamster cells in vitro, and these transformed cells will produce tumors when injected into newborn hamsters. This finding, taken in conjunction with other studies (Graham et al., this volume; McAllister et al., 1969; McDougall et al., this volume; Williams 1973), suggests that the categorization of Ad2 and Ad5 as \"nononcogenic\" viruses is a reflection of host response rather than an intrinsic property of the viruses. However, transformation of hamster cells by Ad2 is inefficient, requiring 10(7)-10(8) PFU to produce a focus of transformed cells. Transformation of hamster kidney cells by the nondefective hybrids cannot be associated with portions of the SV40 genome. During the transformation process, complex interactions must occur between the hamster cell genome and the viral genome of Ad2 or the nondefective hybrids. Thus while it appears that there is very little Ad2 DNA in one nonhybrid Ad2-transformed cell line, there is a larger amount of Ad2 DNA in all of the hybrid virus-transformed cell lines. Moreover, while one Ad2+ND2-transformed line has apparently lost the SV40 portion of the viral genome, it is present and transcribed in another line transformed by the same virus. Finally, in the lines of nondefective hybrid-transformed cells examined thus far, there is extensive transcription from the Ad2 H strand. This pattern of transcription differs from transcription of the viral genome in most hybrid Ad2-transformed hamster and rat cells in which L-strand transcripion predominates."} {"id": "PMID:169099", "title": "Characterization of defective simian virus 40 DNA: comparison between large-plaque and small-plaque types.", "content": "We characterized defective DNA molecules of large-plaque and small-plaque SV40 produced and accumulated during serial undiluted passages. The electron microscope heteroduplex method revealed that defective SV40 DNA contains deletions, insertions and substitutions. The majority of the large-plaque defective molecules had a simple deletion. The deletions were heterogeneous in size, and the sites of deletion appeared to be mostly overlapping. The majority of the small-plaque defective molecules had a deletion, and more than half of the deletion molecules also had an insertion at a separate site. The small-plaque SV40 genome appeared to have more sites for deletion to occur than large-plaque SV40, and the deletions have occurred at more than two sites. The change of a local nucleo tide sequence resulting from mutation may be related to the difference between the two plaque types.", "contents": "Characterization of defective simian virus 40 DNA: comparison between large-plaque and small-plaque types. We characterized defective DNA molecules of large-plaque and small-plaque SV40 produced and accumulated during serial undiluted passages. The electron microscope heteroduplex method revealed that defective SV40 DNA contains deletions, insertions and substitutions. The majority of the large-plaque defective molecules had a simple deletion. The deletions were heterogeneous in size, and the sites of deletion appeared to be mostly overlapping. The majority of the small-plaque defective molecules had a deletion, and more than half of the deletion molecules also had an insertion at a separate site. The small-plaque SV40 genome appeared to have more sites for deletion to occur than large-plaque SV40, and the deletions have occurred at more than two sites. The change of a local nucleo tide sequence resulting from mutation may be related to the difference between the two plaque types."} {"id": "PMID:169104", "title": "Endotracheal antibiotics for the prevention of tracheobronchial infections in tracheotomized unconscious patients. A comparative study of gentamicin and aminosidin-polymyxin B combination.", "content": "Endotracheal administration of gentamicin has been compared to the endotracheal administration of aminosidin plus polymyxin B as a preventive measure against tracheobronchial infections in 25 and 22 tracheotomized patients respectively who had been admitted to a neurosurgical unit. Both series were comparable as far as underlying disease, duration of hospitalization, surgical therapy. Both regimens were similarly effective from the bacteriologic and clinical points of view. Both regimens were similarly effective in preventing colonization of bronchial secretions by potential pathogens and were associated with a similar frequency of infectious episodes (eight in each group). The use of aminosidin-polymyxin B combination was associated with a lower incidence of emergence of gentamicin resistant strains, but the endotracheal administration of gentamicin was better tolerated than that of the combination. It is concluded that the combination of aminosidin-polymyxin is a useful alternative to gentamicin for the prevention of bronchopulmonary infections in unconscious tracheotomized patients.", "contents": "Endotracheal antibiotics for the prevention of tracheobronchial infections in tracheotomized unconscious patients. A comparative study of gentamicin and aminosidin-polymyxin B combination. Endotracheal administration of gentamicin has been compared to the endotracheal administration of aminosidin plus polymyxin B as a preventive measure against tracheobronchial infections in 25 and 22 tracheotomized patients respectively who had been admitted to a neurosurgical unit. Both series were comparable as far as underlying disease, duration of hospitalization, surgical therapy. Both regimens were similarly effective from the bacteriologic and clinical points of view. Both regimens were similarly effective in preventing colonization of bronchial secretions by potential pathogens and were associated with a similar frequency of infectious episodes (eight in each group). The use of aminosidin-polymyxin B combination was associated with a lower incidence of emergence of gentamicin resistant strains, but the endotracheal administration of gentamicin was better tolerated than that of the combination. It is concluded that the combination of aminosidin-polymyxin is a useful alternative to gentamicin for the prevention of bronchopulmonary infections in unconscious tracheotomized patients."} {"id": "PMID:169105", "title": "Acquired tracheomalacia: etiology and differential diagnosis.", "content": "The noninvasive diagnosis of impaired mechanical integrity or compliance of the trachea is most accurately made by fluoroscopic observation recorded on video tape or cineradiography, with or without benefit of artificial contrast media (contrast tracheography). In particular, localized buckling, collapse or dilatation indicative of focal tracheomalacia may thus be diagnosed in vivo and correlated with diseases of the central airways. Congenital tracheomalacia is a rare, bu, well described entity. Cases of acquired tracheomalacia occur with increasing frequency, but are often not clearly recognized. We contrast the dynamic behavior of the normal trachea with the abnormal dynamics characteristic of focal tracheomalacia. Such lesions may result from trauma, surgical procedures, chronic irritation, inflammation, mechanical changes, or malignancy.", "contents": "Acquired tracheomalacia: etiology and differential diagnosis. The noninvasive diagnosis of impaired mechanical integrity or compliance of the trachea is most accurately made by fluoroscopic observation recorded on video tape or cineradiography, with or without benefit of artificial contrast media (contrast tracheography). In particular, localized buckling, collapse or dilatation indicative of focal tracheomalacia may thus be diagnosed in vivo and correlated with diseases of the central airways. Congenital tracheomalacia is a rare, bu, well described entity. Cases of acquired tracheomalacia occur with increasing frequency, but are often not clearly recognized. We contrast the dynamic behavior of the normal trachea with the abnormal dynamics characteristic of focal tracheomalacia. Such lesions may result from trauma, surgical procedures, chronic irritation, inflammation, mechanical changes, or malignancy."} {"id": "PMID:169106", "title": "Fibrous histiocytoma of the trachea.", "content": "A histologically benign but locally infiltrating tumor of histiocytes, fibrous histiocytoma, was found in the trachea of a 26-year-old man. Partial resection of the trachea afforded the successful removal of the growth with no evidence of recurrence or metastases 27 months after surgery. Pathology and prognostic aspects of the tumor are discussed.", "contents": "Fibrous histiocytoma of the trachea. A histologically benign but locally infiltrating tumor of histiocytes, fibrous histiocytoma, was found in the trachea of a 26-year-old man. Partial resection of the trachea afforded the successful removal of the growth with no evidence of recurrence or metastases 27 months after surgery. Pathology and prognostic aspects of the tumor are discussed."} {"id": "PMID:169107", "title": "Evaluation of different antibiotic actions combined with rifampicin. In vitro synergism against Pseudomonas and Proteus.", "content": "Associations of penicillin, streptomycin, tetracycline and polymyxin B with rifampicin were tested for synergism against Pseudomonas and Proteus pathological strains. The combination of rifampicin and polymyxin B was clearly synergistic for all strains as it was evaluated by isobolograms and killing curvesmthe bactericidal action of this association, without any cross-resistance between its components, may eradicate gram-negative bacteria infections with marked polyvalent drug resistances.", "contents": "Evaluation of different antibiotic actions combined with rifampicin. In vitro synergism against Pseudomonas and Proteus. Associations of penicillin, streptomycin, tetracycline and polymyxin B with rifampicin were tested for synergism against Pseudomonas and Proteus pathological strains. The combination of rifampicin and polymyxin B was clearly synergistic for all strains as it was evaluated by isobolograms and killing curvesmthe bactericidal action of this association, without any cross-resistance between its components, may eradicate gram-negative bacteria infections with marked polyvalent drug resistances."} {"id": "PMID:169108", "title": "Studies on the additive effect of polymyxin B and the bactericidal activity of human serum against Serratia marcescens.", "content": "Two of twelve examined S. marcescens strains were promptly killed by 80% (v/v) fresh human serum (within 20 min), analogous to a serum-sensitive control strain of Escherichia coli; ten strains, however, were killed by fresh serum only after extended incubation (2-4 h). The combination of therapeutically achievable concentrations of polymyxin B (range 5 to 1.25 mug/ml) and fresh, but not heat-inactivated human serum was found to exert an accelerated, additive effect against 9 of 10 'delayed serum-sensitive' isolates of S. marcescens, an organism that is characterized by intrinsic resistance against polymyxins. The combination of 80% (v/v) fresh, defibrinated human blood and polymyxin B likewise resulted in an additive effect. Polymyxin B treatment of S. marcescens strains caused a prompt, marked, though reversible bile salt susceptibility of the cells; in contrast, the effect induced by fresh serum was slight and not apparent until several hours after exposure.", "contents": "Studies on the additive effect of polymyxin B and the bactericidal activity of human serum against Serratia marcescens. Two of twelve examined S. marcescens strains were promptly killed by 80% (v/v) fresh human serum (within 20 min), analogous to a serum-sensitive control strain of Escherichia coli; ten strains, however, were killed by fresh serum only after extended incubation (2-4 h). The combination of therapeutically achievable concentrations of polymyxin B (range 5 to 1.25 mug/ml) and fresh, but not heat-inactivated human serum was found to exert an accelerated, additive effect against 9 of 10 'delayed serum-sensitive' isolates of S. marcescens, an organism that is characterized by intrinsic resistance against polymyxins. The combination of 80% (v/v) fresh, defibrinated human blood and polymyxin B likewise resulted in an additive effect. Polymyxin B treatment of S. marcescens strains caused a prompt, marked, though reversible bile salt susceptibility of the cells; in contrast, the effect induced by fresh serum was slight and not apparent until several hours after exposure."} {"id": "PMID:169109", "title": "In vitro and in vivo effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on types 1 and 3 parainfulenza virus infections.", "content": "1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) had significant in vitro activity against type 1 parainfluenza (Sendai) and type 3 parainogenic (HA-1) viruses. Activity was manifested as inhibition of both viral cytopathogenic effect and of recoverable virus or viral hemagglutinin titer. The minimum Sendai virus inhibitory concentration was determined to be approximately 3.2 mug/ml. Previous studies had determined the minimum concentration inhibiting HA-1 virus was approximately 1-10 mug/ml. The effect of time of addition of ribavirin to virus-infected cells was determined; maximal activity was seen when the drug added just prior to either virus or within 4-8 h after each virus, although anti-Senadi viral effects were still apparent when ribavirin was added as late as 24 h after the virus. Ribavirin had no effect on adsorption of HA-1 or Sendai virus to cells. Lethal Sendai virus infections of mice were significantly inhibited by multiple intraperitoneal ribavirin treatment, starting either 4 h before or up to 24 h after virus inoculation. Therapy starting 48, 72 or 96 h after virus exposure had a moderate degree of efficacy. Treatment using an aerosol chamber also was of moderate effectiveness, although the procedure was considered traumatic to the animals. A nonlethal, principally upper respiratory tract infection of hamsters induced by the HA-1 virus was inhibited by ribavirin therapy. Treatment administered intraperitoneally, per os or by aerosol chamber resulted in reduced 23-day antibody titers to the virus, presumably because of reduction of virus in the animal. In a separate experiment, intraperitoneal ribavirin therapy resulted in a 1 log10 or less reduction in virus titer in nasal washings from HA-1 virus-infected hamsters, whereas, when the drug was administered intranasally in a dry powder aerosol spray, nasal virus titers were reduced up to 2 log10 and a moderate virus-induced lung consolidation was completely inhibited.", "contents": "In vitro and in vivo effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on types 1 and 3 parainfulenza virus infections. 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) had significant in vitro activity against type 1 parainfluenza (Sendai) and type 3 parainogenic (HA-1) viruses. Activity was manifested as inhibition of both viral cytopathogenic effect and of recoverable virus or viral hemagglutinin titer. The minimum Sendai virus inhibitory concentration was determined to be approximately 3.2 mug/ml. Previous studies had determined the minimum concentration inhibiting HA-1 virus was approximately 1-10 mug/ml. The effect of time of addition of ribavirin to virus-infected cells was determined; maximal activity was seen when the drug added just prior to either virus or within 4-8 h after each virus, although anti-Senadi viral effects were still apparent when ribavirin was added as late as 24 h after the virus. Ribavirin had no effect on adsorption of HA-1 or Sendai virus to cells. Lethal Sendai virus infections of mice were significantly inhibited by multiple intraperitoneal ribavirin treatment, starting either 4 h before or up to 24 h after virus inoculation. Therapy starting 48, 72 or 96 h after virus exposure had a moderate degree of efficacy. Treatment using an aerosol chamber also was of moderate effectiveness, although the procedure was considered traumatic to the animals. A nonlethal, principally upper respiratory tract infection of hamsters induced by the HA-1 virus was inhibited by ribavirin therapy. Treatment administered intraperitoneally, per os or by aerosol chamber resulted in reduced 23-day antibody titers to the virus, presumably because of reduction of virus in the animal. In a separate experiment, intraperitoneal ribavirin therapy resulted in a 1 log10 or less reduction in virus titer in nasal washings from HA-1 virus-infected hamsters, whereas, when the drug was administered intranasally in a dry powder aerosol spray, nasal virus titers were reduced up to 2 log10 and a moderate virus-induced lung consolidation was completely inhibited."} {"id": "PMID:169110", "title": "Antiviral activity of a pyrazino-pyrazine derivative.", "content": "The 2,3-dihydroxy-6-bromo-pyrazino-[2,3-beta]-pyrazine is a substance selected during the antiviral screening of pyrazino-pyrazine derivatives. The compound shows antiviral activity in vitro against measles, NDV, some influenza viruses and against herpes simplex and zoster, infectious canine hepatitis and vaccinia viruses. It had no effect on ECHO 9 virus. Therapeutic trials showed activity also on herpetic keratoconjunctivitis experimentally induced in rabbits.", "contents": "Antiviral activity of a pyrazino-pyrazine derivative. The 2,3-dihydroxy-6-bromo-pyrazino-[2,3-beta]-pyrazine is a substance selected during the antiviral screening of pyrazino-pyrazine derivatives. The compound shows antiviral activity in vitro against measles, NDV, some influenza viruses and against herpes simplex and zoster, infectious canine hepatitis and vaccinia viruses. It had no effect on ECHO 9 virus. Therapeutic trials showed activity also on herpetic keratoconjunctivitis experimentally induced in rabbits."} {"id": "PMID:169112", "title": "[Persistence of latex-agglutination inhibiting and neutralizing antibodies against enterovirus in the healthy population (author's transl)].", "content": "Sera of 122 persons were examined by the neutralization and latex-agglutination inhibition tests for antibodies against Polio type I, Coxsackie virus type A 9 and B 4, as well as Echo virus type 9. With increasing age there was a titre difference between latex-agglutination inhibiting and neutralizing antibodies, due to the earlier fall in the former. These antibodies, contrary to neutralizing ones, were in the lower titre region. The results confirmed the usefulness of the latex-agglutination inhibition test in the diagnosis of acute enterovirus infections.", "contents": "[Persistence of latex-agglutination inhibiting and neutralizing antibodies against enterovirus in the healthy population (author's transl)]. Sera of 122 persons were examined by the neutralization and latex-agglutination inhibition tests for antibodies against Polio type I, Coxsackie virus type A 9 and B 4, as well as Echo virus type 9. With increasing age there was a titre difference between latex-agglutination inhibiting and neutralizing antibodies, due to the earlier fall in the former. These antibodies, contrary to neutralizing ones, were in the lower titre region. The results confirmed the usefulness of the latex-agglutination inhibition test in the diagnosis of acute enterovirus infections."} {"id": "PMID:169114", "title": "[Carcinoma of the liver in a child after seven-year complete remission of acute lymphoblastic leukaemia(author's transl)].", "content": "A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.", "contents": "[Carcinoma of the liver in a child after seven-year complete remission of acute lymphoblastic leukaemia(author's transl)]. A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris."} {"id": "PMID:169115", "title": "[Inhibition of ethanol exidation on prolonged fasting in man: reversibility on fructose infusion(author's transl)].", "content": "Fasting for over 36 hours was found to inhibit ethanol metabolism in healthy volunteers by 43% (P less than 0.01) compared with values obtained after 12 hours' fasting. Ethanol oxidation was not inhibited by prolonged fasting when it was stimulated by intravenous fructose. The explanation for this effect is thought to lie in the inhibition of alcohol oxidation mainly by limiting the rate of NADH-reoxidation in the liver.", "contents": "[Inhibition of ethanol exidation on prolonged fasting in man: reversibility on fructose infusion(author's transl)]. Fasting for over 36 hours was found to inhibit ethanol metabolism in healthy volunteers by 43% (P less than 0.01) compared with values obtained after 12 hours' fasting. Ethanol oxidation was not inhibited by prolonged fasting when it was stimulated by intravenous fructose. The explanation for this effect is thought to lie in the inhibition of alcohol oxidation mainly by limiting the rate of NADH-reoxidation in the liver."} {"id": "PMID:169120", "title": "Corticosterone-induced changes in hypothalamic corticotropin-releasing factor (CRF) content after stress.", "content": "Central and peripheral humoral responses of the adrenocortical system were measured for 2 h after the application of several stimuli. Two min after the onset of the stresses of sham-adrenalectomy or laparotomy with intestinal traction there was a 4-6 fold increase in hypothalamic CRF content as compared to control content, This is the usual CRF response to stress. In contrast, after adrenalectomy or manipulation of the pedicles of adrenal glands; CRF content at 2 min was only slightly increased above baseline values. This finding suggests that touching the adrenal vascular and nervous supply results in a direct neural input to the hypothalamus that is qualitatively different from most other stimuli. At times later than 2 min after stress, whem plasma corticosterone levels rise in the intact rat, the patterns of CRF and ACTH responses that were observed after adrenalectomy were determined by whether corticosterone replacement therapy was given. Without corticosterone replacement, the CRF and ACTH responses to adrenalectomy resembled those of laparotomy with intestinal traction. When corticosterone was administered 2 and 40 min after adrenalectomy, the CRF and ACTH responses resembled those of sham-adrenalectomy. At 20 min, CRF content was low after laparotomy with intestinal traction or adrenalectomy and high after shan-adrenalectomy or adrenalectomy with corticosterone replacement. Plasma ACTH peaked by 20 min, and remained high for 2 h after the first 2 stimuli, and was significantly decreased from the 20 min peak by 40 min after application of the latter stimuli. CRF content increased to a second peak 80 min after laparotomy with intestinal traction or adrenalectomy. This rise in CRF must represent increased formation of the releasing factor because ACTH levels were elevated and constant for the preceding 60 min. After sham-adrenalectomy or adrenalectomy with corticosterone replacement, CRF content and ACTH are low at 80 min. Measurement of circulating ACTH levels in conjunction with CRF content after these stimuli have yielded sufficient information to assign mechanisms of altered synthesis and secretion to explain the observed changes in CRF content. Corticosterone damps the adrenocortical system response to the stimuli of sham-adrenalectomy or adrenalectomy with corticosterone replacement by two mechanisms. Firstly, it acts to inhibit CRF secretion probably via rate-sensitive feedback. Secondly, it acts to inhibit the second wave of CRF formation that is observed 80 min after stress is applied, probably via the proportional feedback mechanism.", "contents": "Corticosterone-induced changes in hypothalamic corticotropin-releasing factor (CRF) content after stress. Central and peripheral humoral responses of the adrenocortical system were measured for 2 h after the application of several stimuli. Two min after the onset of the stresses of sham-adrenalectomy or laparotomy with intestinal traction there was a 4-6 fold increase in hypothalamic CRF content as compared to control content, This is the usual CRF response to stress. In contrast, after adrenalectomy or manipulation of the pedicles of adrenal glands; CRF content at 2 min was only slightly increased above baseline values. This finding suggests that touching the adrenal vascular and nervous supply results in a direct neural input to the hypothalamus that is qualitatively different from most other stimuli. At times later than 2 min after stress, whem plasma corticosterone levels rise in the intact rat, the patterns of CRF and ACTH responses that were observed after adrenalectomy were determined by whether corticosterone replacement therapy was given. Without corticosterone replacement, the CRF and ACTH responses to adrenalectomy resembled those of laparotomy with intestinal traction. When corticosterone was administered 2 and 40 min after adrenalectomy, the CRF and ACTH responses resembled those of sham-adrenalectomy. At 20 min, CRF content was low after laparotomy with intestinal traction or adrenalectomy and high after shan-adrenalectomy or adrenalectomy with corticosterone replacement. Plasma ACTH peaked by 20 min, and remained high for 2 h after the first 2 stimuli, and was significantly decreased from the 20 min peak by 40 min after application of the latter stimuli. CRF content increased to a second peak 80 min after laparotomy with intestinal traction or adrenalectomy. This rise in CRF must represent increased formation of the releasing factor because ACTH levels were elevated and constant for the preceding 60 min. After sham-adrenalectomy or adrenalectomy with corticosterone replacement, CRF content and ACTH are low at 80 min. Measurement of circulating ACTH levels in conjunction with CRF content after these stimuli have yielded sufficient information to assign mechanisms of altered synthesis and secretion to explain the observed changes in CRF content. Corticosterone damps the adrenocortical system response to the stimuli of sham-adrenalectomy or adrenalectomy with corticosterone replacement by two mechanisms. Firstly, it acts to inhibit CRF secretion probably via rate-sensitive feedback. Secondly, it acts to inhibit the second wave of CRF formation that is observed 80 min after stress is applied, probably via the proportional feedback mechanism."} {"id": "PMID:169121", "title": "Competitive binding activity of angiotensin II analogues in an adrenal cortex radioligand-receptor assay;.", "content": "The competitive binding activities of a number of angiotensin analogues were determined in a radioligand-receptor assay employing bovine adrenal crotex homogenate and [125I] iodoangiotensin II. This assay system has been shown to provide a precise and convenient method for evaluation and comparison of the binding-inhibition potencies of angiotensin II derivatives with agonist and antagonist activities. Agonist analogues of angiotensin II showed competitive binding activities in proportion to their known biological activities upon aldosterone production by the adrenal zona glomerulosa. Thus, the [Des-Asp1] heptapeptide of angiotensin II was equipotent with the native octapeptide in terms of binding-inhibition activity, and the [Sar1] derivative of angiotensin II was more potent than the native peptide. By contrast, the [Des-Asp1, Des-Arg2] hexapeptide and the [Des-Phe8] heptapeptide showed less than 1% of the activity of angiotensin II. Angiotensin II antagonists formed by C-terminal substitution of the octapeptide with isoleucine or alanine were also found to exhibit binding-inhibition activities in proportion to their known potencies as antagonists of the action of angiotensin II upon smooth muscle. Certain antagonists, such as [1-guanidoacetic, 8-isoleucine]-angiotensin II and [1-sarcosine, 8-isoleucine]-angiotensin II displayed significantly greater binding-inhibition potency than E1Asp1, Ileu5,-angiotensin II in the adrenal receptor system. Several, such as [Sar1, Ala8]-angiotensin II and [MeAla1, Ileu8]-antiotensin II were approximately equipotent with angiotensin II, while others such as [1-succinic acid, 8-alanine]-angiotensin II and [D-Ileu8]-angiotensin II showed no significant binding-inhibition activity. The relative binding-inhibition potencies of the antagonist peptides showed a general correlation with the pA2 values of the same components determined upon the smooth muscle response of the isolated aortic strip. The binding-inhibition potency of angiotensin II antagonists was also strongly influenced by the charge of the N-terminal residue, with enhancement of activity by more basic substituents and abolition of activity by highly acidic residues. The influence of the basicity of the N-terminus upon receptor binding was also observed with the agonist analogue [Sar1]-angiotensin II, which showed a 2- to 3-fold increase in binding-inhibition potency in comparison to native angiotensin II. The significant enhancement of binding-inhibition potency by N-terminal sarcosine substitution is attributable to higher affinity of the modified peptide for the angiotensin II receptor site, and is consistent with the increased activity of [Sar1]-angiotensin II upon smooth muscle and aldosterone production in vitro. The determination of binding-inhibition activity in the adrenal radioligand receptor assay provides a valid and convenient method for analysis of the role of binding affinity in the actions of competitive antagonists upon the responses of target cells to angiotensin II.", "contents": "Competitive binding activity of angiotensin II analogues in an adrenal cortex radioligand-receptor assay;. The competitive binding activities of a number of angiotensin analogues were determined in a radioligand-receptor assay employing bovine adrenal crotex homogenate and [125I] iodoangiotensin II. This assay system has been shown to provide a precise and convenient method for evaluation and comparison of the binding-inhibition potencies of angiotensin II derivatives with agonist and antagonist activities. Agonist analogues of angiotensin II showed competitive binding activities in proportion to their known biological activities upon aldosterone production by the adrenal zona glomerulosa. Thus, the [Des-Asp1] heptapeptide of angiotensin II was equipotent with the native octapeptide in terms of binding-inhibition activity, and the [Sar1] derivative of angiotensin II was more potent than the native peptide. By contrast, the [Des-Asp1, Des-Arg2] hexapeptide and the [Des-Phe8] heptapeptide showed less than 1% of the activity of angiotensin II. Angiotensin II antagonists formed by C-terminal substitution of the octapeptide with isoleucine or alanine were also found to exhibit binding-inhibition activities in proportion to their known potencies as antagonists of the action of angiotensin II upon smooth muscle. Certain antagonists, such as [1-guanidoacetic, 8-isoleucine]-angiotensin II and [1-sarcosine, 8-isoleucine]-angiotensin II displayed significantly greater binding-inhibition potency than E1Asp1, Ileu5,-angiotensin II in the adrenal receptor system. Several, such as [Sar1, Ala8]-angiotensin II and [MeAla1, Ileu8]-antiotensin II were approximately equipotent with angiotensin II, while others such as [1-succinic acid, 8-alanine]-angiotensin II and [D-Ileu8]-angiotensin II showed no significant binding-inhibition activity. The relative binding-inhibition potencies of the antagonist peptides showed a general correlation with the pA2 values of the same components determined upon the smooth muscle response of the isolated aortic strip. The binding-inhibition potency of angiotensin II antagonists was also strongly influenced by the charge of the N-terminal residue, with enhancement of activity by more basic substituents and abolition of activity by highly acidic residues. The influence of the basicity of the N-terminus upon receptor binding was also observed with the agonist analogue [Sar1]-angiotensin II, which showed a 2- to 3-fold increase in binding-inhibition potency in comparison to native angiotensin II. The significant enhancement of binding-inhibition potency by N-terminal sarcosine substitution is attributable to higher affinity of the modified peptide for the angiotensin II receptor site, and is consistent with the increased activity of [Sar1]-angiotensin II upon smooth muscle and aldosterone production in vitro. The determination of binding-inhibition activity in the adrenal radioligand receptor assay provides a valid and convenient method for analysis of the role of binding affinity in the actions of competitive antagonists upon the responses of target cells to angiotensin II."} {"id": "PMID:169122", "title": "Degradation of thyrotropin-releasing hormone by the GH3 strain of pituitary cells in culture.", "content": "Thyrotropin-releasing hormone (TRH), pGlu-His-ProNH2, binds within 1 h to specific receptors on the GH3 strain of pituitary cells. When GH3 cells were incubated for 2 days with 3 nM [2,3-3H-Pro]TRH, an increasing fraction of the total cellular radioactivity (7% after 1 h, 81% after 43 h) was associated covalently with proteins as determined by dialysis, acid precipitation, and gel filtration; this fraction corresponded to label which could not be displaced from intact GH3 cells by the addition of excess unlabeled TRH. R5 and GH12C1 cells, strains which lack TRH receptors, accumulated 16 or 23%, respectively, as much label from [2,3-3H-Pro]TRH as did GH3 cells in 24 h. After 24 h of incubation with [2,3-3H-Pro]TRH and [14C-His]TRH, the ratio of 14C/3H in GH3 cells was the same as in the culture medium, indicating that the intact tripeptide was taken up by the cells. After 24-48 h of incubation with [2,3-3H-Pro]TRH, GH3 proteins appeared to be labeled randomly as surmised by fractionation on Sephadex G-100, DEAE cellulose, Sepharose 4B and sucrose density gradients. In cultures treated with cycloheximide (10 mug/ml) or proline (6.3 mM) the initial binding of [2,3-3H-Pro]TRH to receptors, measured after 1 h, was 97% or 102% of control. However, the incorporation of label from [2,3-3H-Pro]TRH into an acid-precipitable product after 22 h was inhibited by 81 and 74% by cycloheximide (1 mug/ml) and proline (2.5 mM). Formation of [2,3-3H] proline from [2,3-?3H-Pro] TRH was demonstrated by thin layer chromatography; the percentage of non-protein radioactivity with an Rf of proline increased from 20 to 80% in GH3 cells incubated 1 or 24 h with [2,3-3H-Pro]TRH. We conclude that after binding to receptors on GH3 cells, TRH is slowly metabolized to its constituent amino acids, and the products [2,3-3H]proline or [14C]histidine are incorporated into newly synthesized proteins.", "contents": "Degradation of thyrotropin-releasing hormone by the GH3 strain of pituitary cells in culture. Thyrotropin-releasing hormone (TRH), pGlu-His-ProNH2, binds within 1 h to specific receptors on the GH3 strain of pituitary cells. When GH3 cells were incubated for 2 days with 3 nM [2,3-3H-Pro]TRH, an increasing fraction of the total cellular radioactivity (7% after 1 h, 81% after 43 h) was associated covalently with proteins as determined by dialysis, acid precipitation, and gel filtration; this fraction corresponded to label which could not be displaced from intact GH3 cells by the addition of excess unlabeled TRH. R5 and GH12C1 cells, strains which lack TRH receptors, accumulated 16 or 23%, respectively, as much label from [2,3-3H-Pro]TRH as did GH3 cells in 24 h. After 24 h of incubation with [2,3-3H-Pro]TRH and [14C-His]TRH, the ratio of 14C/3H in GH3 cells was the same as in the culture medium, indicating that the intact tripeptide was taken up by the cells. After 24-48 h of incubation with [2,3-3H-Pro]TRH, GH3 proteins appeared to be labeled randomly as surmised by fractionation on Sephadex G-100, DEAE cellulose, Sepharose 4B and sucrose density gradients. In cultures treated with cycloheximide (10 mug/ml) or proline (6.3 mM) the initial binding of [2,3-3H-Pro]TRH to receptors, measured after 1 h, was 97% or 102% of control. However, the incorporation of label from [2,3-3H-Pro]TRH into an acid-precipitable product after 22 h was inhibited by 81 and 74% by cycloheximide (1 mug/ml) and proline (2.5 mM). Formation of [2,3-3H] proline from [2,3-?3H-Pro] TRH was demonstrated by thin layer chromatography; the percentage of non-protein radioactivity with an Rf of proline increased from 20 to 80% in GH3 cells incubated 1 or 24 h with [2,3-3H-Pro]TRH. We conclude that after binding to receptors on GH3 cells, TRH is slowly metabolized to its constituent amino acids, and the products [2,3-3H]proline or [14C]histidine are incorporated into newly synthesized proteins."} {"id": "PMID:169123", "title": "The significance of calcium for glucose stimulation of insulin release.", "content": "The significance of Ca++ for glucose stimulation of insulin release was studied in an in vitro system with beta-cell-rich pancreatic islets microdissected from oh/ob-mice. There was only a slight depression of cAMP in islets exposed to the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine after withdrawal of Ca++ from the incubation medium. The lack of a stimulatory effect of glucose noted in the absence of extracellular Ca++ is therefore probably accounted for by factors other than impaired adenylate cyclase activity. A rise of extracellular Ca++ above the concentration necessary for obtaining the optimal secretagogic effect of glucose resulted in inhibition of the glucose-stimulated insulin release, leaving basal secretions and islet contents of cAMP unaffected. Evidence was provided in support of the idea that H+ completes for Ca++ in glucose stimulation of insulin release. Both the rate of basal insulin release and that seen after stimulation with glucose were diminished by about 50% after introducing 0.2 mM La+++ in the incubation medium. These observations emphasize the significant role of Ca++ in the regulation of insulin secretion, suggesting that not only a decrease but also an increase of the functionally important intracellular pool(s) of Ca++ can result in a diminished response to glucose.", "contents": "The significance of calcium for glucose stimulation of insulin release. The significance of Ca++ for glucose stimulation of insulin release was studied in an in vitro system with beta-cell-rich pancreatic islets microdissected from oh/ob-mice. There was only a slight depression of cAMP in islets exposed to the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine after withdrawal of Ca++ from the incubation medium. The lack of a stimulatory effect of glucose noted in the absence of extracellular Ca++ is therefore probably accounted for by factors other than impaired adenylate cyclase activity. A rise of extracellular Ca++ above the concentration necessary for obtaining the optimal secretagogic effect of glucose resulted in inhibition of the glucose-stimulated insulin release, leaving basal secretions and islet contents of cAMP unaffected. Evidence was provided in support of the idea that H+ completes for Ca++ in glucose stimulation of insulin release. Both the rate of basal insulin release and that seen after stimulation with glucose were diminished by about 50% after introducing 0.2 mM La+++ in the incubation medium. These observations emphasize the significant role of Ca++ in the regulation of insulin secretion, suggesting that not only a decrease but also an increase of the functionally important intracellular pool(s) of Ca++ can result in a diminished response to glucose."} {"id": "PMID:169124", "title": "The effect of castration and testosterone replacement on specific proteins and androgen levels of the rat epididymis.", "content": "The normal weight increase of the epididymis during sexual maturation and its maintenance through adulthood were found to be dependent on the provision of androgens. Binding of [3H]dihydrotestosterone (DHT) to the epididymal 8S cytoplasmic receptor gradually decreased after castration to become undetectable after 25 days. Binding to the androgen binding protein (ABP) was absent 4 days after castration and was not reinduced by 3 weeks of testosterone (T) administration. Unilateral castration for periods of up to 27 days showed the disappearance of ABP with preservation of the 8S receptor on the castrated side, indicating a testicular source for ABP and the epididymal origin of the 8S receptor. The tissue concentrations of T and DHT in the epididymis became undetectable 30 days after castration and were restored to normal values by administration of testosterone in large doses (1.5 mg/100 g BW). Similar results were obtained in rats castrated at 10 days of age and injected with testosterone until 60 days old. The ratio DHT/T was depressed in the castrate and increased with testosterone treatment. The protein content of the epididymis (mg of protein/g wet weight) was also found to be influenced by androgens. Our results show evidence of some mechanisms involved in the trophic effect of androgens upon the epididymis and suggest the possible androgenic control of epididymal 5alpha-reductase activity. They also indicate that a testicular factor is required for the maintenance of the 8S cytoplasmic androgen receptor. It is not known whether this factor is testosterone or some other testicular secretion.", "contents": "The effect of castration and testosterone replacement on specific proteins and androgen levels of the rat epididymis. The normal weight increase of the epididymis during sexual maturation and its maintenance through adulthood were found to be dependent on the provision of androgens. Binding of [3H]dihydrotestosterone (DHT) to the epididymal 8S cytoplasmic receptor gradually decreased after castration to become undetectable after 25 days. Binding to the androgen binding protein (ABP) was absent 4 days after castration and was not reinduced by 3 weeks of testosterone (T) administration. Unilateral castration for periods of up to 27 days showed the disappearance of ABP with preservation of the 8S receptor on the castrated side, indicating a testicular source for ABP and the epididymal origin of the 8S receptor. The tissue concentrations of T and DHT in the epididymis became undetectable 30 days after castration and were restored to normal values by administration of testosterone in large doses (1.5 mg/100 g BW). Similar results were obtained in rats castrated at 10 days of age and injected with testosterone until 60 days old. The ratio DHT/T was depressed in the castrate and increased with testosterone treatment. The protein content of the epididymis (mg of protein/g wet weight) was also found to be influenced by androgens. Our results show evidence of some mechanisms involved in the trophic effect of androgens upon the epididymis and suggest the possible androgenic control of epididymal 5alpha-reductase activity. They also indicate that a testicular factor is required for the maintenance of the 8S cytoplasmic androgen receptor. It is not known whether this factor is testosterone or some other testicular secretion."} {"id": "PMID:169125", "title": "Regulation of in vitro insulin release from a transplantable Syrian hamster insulinoma.", "content": "An insulin-producing islet cell tumor of the Syrian hamster has been studied in vitro for its capacity to respond to known stimuli of insulin release. Insulin secretion during short term incubation and perifusion of fragments of tumor was detected by radioimmunoassay. Insulin release was increased 2-4 fold by 40 mM potassium in the presence of calcium, glucose (22 mM), glucagon (0.3-3.0 muM), N6,02'-dibutyryl adenosine 3',5'-monophosphate (cAMP; 6mM), and theophylline (10 mM). Concentrations of glucagon that induced insulin release were also effective in activating adenylate cyclase in the membranes of tumor cells. Thus, this tumor appears to possess a cAMP-mediated mechanism for insulin release. Somatostatin (0.8-25 mum) inhibited glucagon-induced insulin release without altering basal or glucagon stimulated adenylate cyclase activity. It would appear that inhibition of glucagon induced insulin release by somatostatin is not mediated by adenylate cyclase. We propose that insulin release by this tumor is sufficiently similar to that found in normal islets so as to make it a suitable model for biochemical studies that require large quantities of homogeneous tissue.", "contents": "Regulation of in vitro insulin release from a transplantable Syrian hamster insulinoma. An insulin-producing islet cell tumor of the Syrian hamster has been studied in vitro for its capacity to respond to known stimuli of insulin release. Insulin secretion during short term incubation and perifusion of fragments of tumor was detected by radioimmunoassay. Insulin release was increased 2-4 fold by 40 mM potassium in the presence of calcium, glucose (22 mM), glucagon (0.3-3.0 muM), N6,02'-dibutyryl adenosine 3',5'-monophosphate (cAMP; 6mM), and theophylline (10 mM). Concentrations of glucagon that induced insulin release were also effective in activating adenylate cyclase in the membranes of tumor cells. Thus, this tumor appears to possess a cAMP-mediated mechanism for insulin release. Somatostatin (0.8-25 mum) inhibited glucagon-induced insulin release without altering basal or glucagon stimulated adenylate cyclase activity. It would appear that inhibition of glucagon induced insulin release by somatostatin is not mediated by adenylate cyclase. We propose that insulin release by this tumor is sufficiently similar to that found in normal islets so as to make it a suitable model for biochemical studies that require large quantities of homogeneous tissue."} {"id": "PMID:169126", "title": "Renal receptors for calcitonin: coordinate occurrence with calcitonin-activated adenylate cyclase.", "content": "High affinity binding of 125I-labeled salmon calcitonin ([125I]SCT) and calcitonin-activated adenylate cyclase were detectable in renal plasma membranes from the rat. Addition of 5'-guanylyl-imidodiphosphate lowered the threshold for enzyme activation by peptide hormones. Renal plasma membranes from man, dog and cow contained little or no calcitonin-sensitive adenylate cyclase and showed no high affinity binding of [125I]SCT. High affinity binding sites were distributed during membrane fractionation in fractions where the specific activity of hormone-sensitive adenylate cyclase was greatest. Calcitonin binding and activation of the adenylate cyclase enzyme occurred at similar hormone concentrations. The relative potencies of calcitonin analogues were similar whether measured by competition for high affinity binding sites or by effect on adenylate cyclase. Low concentrations of Lubrol-PX, a nonionic detergent, did not affect catalytic function of the enzyme determined in the presence of sodium fluoride but caused parallel loss of high affinity [125I]SCT binding and hormonal sensitivity of the enzyme. This observation provided further evidence that interaction of calcitonin with specific receptors (identified with [125I]SCT binding) is essential for calcitonin activation of adenylate cyclase, but showed that catalytic activity of enzyme does not require functioning hormone receptors.", "contents": "Renal receptors for calcitonin: coordinate occurrence with calcitonin-activated adenylate cyclase. High affinity binding of 125I-labeled salmon calcitonin ([125I]SCT) and calcitonin-activated adenylate cyclase were detectable in renal plasma membranes from the rat. Addition of 5'-guanylyl-imidodiphosphate lowered the threshold for enzyme activation by peptide hormones. Renal plasma membranes from man, dog and cow contained little or no calcitonin-sensitive adenylate cyclase and showed no high affinity binding of [125I]SCT. High affinity binding sites were distributed during membrane fractionation in fractions where the specific activity of hormone-sensitive adenylate cyclase was greatest. Calcitonin binding and activation of the adenylate cyclase enzyme occurred at similar hormone concentrations. The relative potencies of calcitonin analogues were similar whether measured by competition for high affinity binding sites or by effect on adenylate cyclase. Low concentrations of Lubrol-PX, a nonionic detergent, did not affect catalytic function of the enzyme determined in the presence of sodium fluoride but caused parallel loss of high affinity [125I]SCT binding and hormonal sensitivity of the enzyme. This observation provided further evidence that interaction of calcitonin with specific receptors (identified with [125I]SCT binding) is essential for calcitonin activation of adenylate cyclase, but showed that catalytic activity of enzyme does not require functioning hormone receptors."} {"id": "PMID:169130", "title": "Antibodies to Epstein-Barr virus in subacute sclerosing panencephalitis patients.", "content": "Blood samples from 45 cases of subacute sclerosing panencephalitis in Israel were tested for the presence of antibodies to Epstein-Barr virus capsid antigen and early antigen by the indirect immunofluorescence method. Significantly higher titers were found in patients as compared to healthy controls with higher titers especially in Jews of Asian-African origin. Mean geometric titer was 1:42.8 in this group as compared to 1:10.8 in the control group. Antibodies to Epstein-Barr Virus early antigen were found in 50% of the patients and in none of the controls tested. Elevated titers of antibodies to Epstein-Barr Virus antigens seem to be related to impaired immunological mechanisms in subacute sclerosing panencephalitis patients, especially of a certain ethnic group.", "contents": "Antibodies to Epstein-Barr virus in subacute sclerosing panencephalitis patients. Blood samples from 45 cases of subacute sclerosing panencephalitis in Israel were tested for the presence of antibodies to Epstein-Barr virus capsid antigen and early antigen by the indirect immunofluorescence method. Significantly higher titers were found in patients as compared to healthy controls with higher titers especially in Jews of Asian-African origin. Mean geometric titer was 1:42.8 in this group as compared to 1:10.8 in the control group. Antibodies to Epstein-Barr Virus early antigen were found in 50% of the patients and in none of the controls tested. Elevated titers of antibodies to Epstein-Barr Virus antigens seem to be related to impaired immunological mechanisms in subacute sclerosing panencephalitis patients, especially of a certain ethnic group."} {"id": "PMID:169142", "title": "Change of the cytochrome oxidase level during exponential growth in Neurospora crassa.", "content": "In Neurospora cells growing in various media, the specific activity of cytochrome oxidase increases very markedly during early exponential growth, reaching a maximum after 4-5 duplication times, then it slowly declines.", "contents": "Change of the cytochrome oxidase level during exponential growth in Neurospora crassa. In Neurospora cells growing in various media, the specific activity of cytochrome oxidase increases very markedly during early exponential growth, reaching a maximum after 4-5 duplication times, then it slowly declines."} {"id": "PMID:169143", "title": "Absence of effects of dibutyryl cyclic guanosine 3',5'-monophosphate on release of alpha-amylase, 45Ca efflux, and protein synthesis in rat pancreas in vitro.", "content": "Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of alpha-amylase from rat pancreas. The nucleotide did not have a significant effect on 45Ca release from the pancreas nor did it alter the response to carbachol. The dibutyryl analogue of cyclic GMP did not duplicate or alter the inhibitory effect of carbachol on 3H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein.", "contents": "Absence of effects of dibutyryl cyclic guanosine 3',5'-monophosphate on release of alpha-amylase, 45Ca efflux, and protein synthesis in rat pancreas in vitro. Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of alpha-amylase from rat pancreas. The nucleotide did not have a significant effect on 45Ca release from the pancreas nor did it alter the response to carbachol. The dibutyryl analogue of cyclic GMP did not duplicate or alter the inhibitory effect of carbachol on 3H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein."} {"id": "PMID:169144", "title": "Microsomal metabolism as a determinant of aflatoxin toxicity.", "content": "The evidences to incriminate the possible role of microsomal drug metabolizing system in aflatoxin toxicity in rat have been reviewed. It is suggested that an effective drug metabolism results in decreased acute toxicity and the products of metabolism are more carcinogenic than the native toxin to the rat liver.", "contents": "Microsomal metabolism as a determinant of aflatoxin toxicity. The evidences to incriminate the possible role of microsomal drug metabolizing system in aflatoxin toxicity in rat have been reviewed. It is suggested that an effective drug metabolism results in decreased acute toxicity and the products of metabolism are more carcinogenic than the native toxin to the rat liver."} {"id": "PMID:169145", "title": "Fetal calf serum alters cyclic adenosine 3',5'-monophosphate's effect on heme synthesis in vitro.", "content": "An investigation of the effect of cAMP on heme synthesis of rat bone marrow cells revealed that at 10(-2) M this cyclic nucleotide inhibits heme synthesis and that optimum stimulation occurs at 10(-4) M. Some unidentified constituent of fetal calf serum in the culture medium modifies the direction and degree of cAMP's effect.", "contents": "Fetal calf serum alters cyclic adenosine 3',5'-monophosphate's effect on heme synthesis in vitro. An investigation of the effect of cAMP on heme synthesis of rat bone marrow cells revealed that at 10(-2) M this cyclic nucleotide inhibits heme synthesis and that optimum stimulation occurs at 10(-4) M. Some unidentified constituent of fetal calf serum in the culture medium modifies the direction and degree of cAMP's effect."} {"id": "PMID:169146", "title": "Appearance of sex hormone receptors in frog (Rana esculenta) tadpole skin during metamorphosis.", "content": "In tadpole skin of Rana esculenta, a specific testosterone receptor was detected during the climax in both males and females. The Kass ranged between 1 and 2.79 x 10(9)M-1.", "contents": "Appearance of sex hormone receptors in frog (Rana esculenta) tadpole skin during metamorphosis. In tadpole skin of Rana esculenta, a specific testosterone receptor was detected during the climax in both males and females. The Kass ranged between 1 and 2.79 x 10(9)M-1."} {"id": "PMID:169148", "title": "Correlation of estrogen-induced uterine eosinophilia with other parameters of estrogen stimulation, produced with estradiol-17beta and estriol.", "content": "Estradiol-17beta is a stronger estrogen than estriol for the genomic response of estrogens. Estriol is a stronger estrogen than estradiol-17beta for the estrogen-induced uterine eosinophilia and the 6 h increase in the uterine wet weight.", "contents": "Correlation of estrogen-induced uterine eosinophilia with other parameters of estrogen stimulation, produced with estradiol-17beta and estriol. Estradiol-17beta is a stronger estrogen than estriol for the genomic response of estrogens. Estriol is a stronger estrogen than estradiol-17beta for the estrogen-induced uterine eosinophilia and the 6 h increase in the uterine wet weight."} {"id": "PMID:169166", "title": "Effect of peripheral ethanol metabolism on the central nervous system.", "content": "The main symptoms of ethanol intoxication, tolerance, and physical dependence presumably, derive from the effects of ethanol on the central nervous system. It is not known clearly how and to what extent these effects are caused by ethanol itself or by its metabolic derivatives, chiefly acetaldehyde, formed in the liver, and transported into the brain through the blood stream. Since the concentrations of acetaldehyde found in the blood and brain of human subjects and experimental animals are approximately 44 times lower than the lowest effective concentrations found in in vitro experiments, it remains to be established whether acetaldehyde derived under in vivo conditions from the oxidation of ethanol in the liver plays any significant role in suppressing the respiratory metabolism or other metabolic pathways in the brain. It is concluded that the site of ethanol effects on the central nervous system is probably associated with that part of the metabolic system that is dependent on normal functioning of the neuronal cell membrane and probably has little relation to the peripheral or central metabolism of ethanol.", "contents": "Effect of peripheral ethanol metabolism on the central nervous system. The main symptoms of ethanol intoxication, tolerance, and physical dependence presumably, derive from the effects of ethanol on the central nervous system. It is not known clearly how and to what extent these effects are caused by ethanol itself or by its metabolic derivatives, chiefly acetaldehyde, formed in the liver, and transported into the brain through the blood stream. Since the concentrations of acetaldehyde found in the blood and brain of human subjects and experimental animals are approximately 44 times lower than the lowest effective concentrations found in in vitro experiments, it remains to be established whether acetaldehyde derived under in vivo conditions from the oxidation of ethanol in the liver plays any significant role in suppressing the respiratory metabolism or other metabolic pathways in the brain. It is concluded that the site of ethanol effects on the central nervous system is probably associated with that part of the metabolic system that is dependent on normal functioning of the neuronal cell membrane and probably has little relation to the peripheral or central metabolism of ethanol."} {"id": "PMID:169167", "title": "Supersensitivity to catecholamines after impairment of extraneuronal uptake or catechol-O-methyl transferase.", "content": "In cat papillary muscle and nictitating membrane block of extraneuronal catechol-O-methyl transferase (COMT) by 3',4'-dihydroxy-alpha-methyl propiophenone (U-0521) or of extraneuronal uptake by hydrocortisone causes supersensitivity to catecholamines whenever the experimental conditions result in a high sensitivity of the organ to catecholamines. After block of monoamine oxidase the extraneuronal O-methylation of (-)-[3H]norepinephrine by the isolated nictiating membrane is due to two O-methylating systems (Km and Vmax: 7.5 muM and 0.73 nmoles - g-1 - min-1, and 131 muM and 8.5 nmoles - g-1 - min-1, respectively). Hydrocortisone (28 muM) blocked the activity of the high affinity system without affecting the low affinity system. Apparently, there exists an extraneuronal compartment of high affinity that has a hydrocortisone-sensitive uptake mechnism; this compartment influences the concentration of catecholamines below the Km of this compartment. Supersensitivity ensues when either uptake or enzyme is blocked. Since the sensitivity effects of U-0521 and hydrocortisone are not additive, the high affinity compartment must a) metabolize most of the catecholamine transported into the compartment, and b) have a limited storage capacity for catecholamines after block of COMT.", "contents": "Supersensitivity to catecholamines after impairment of extraneuronal uptake or catechol-O-methyl transferase. In cat papillary muscle and nictitating membrane block of extraneuronal catechol-O-methyl transferase (COMT) by 3',4'-dihydroxy-alpha-methyl propiophenone (U-0521) or of extraneuronal uptake by hydrocortisone causes supersensitivity to catecholamines whenever the experimental conditions result in a high sensitivity of the organ to catecholamines. After block of monoamine oxidase the extraneuronal O-methylation of (-)-[3H]norepinephrine by the isolated nictiating membrane is due to two O-methylating systems (Km and Vmax: 7.5 muM and 0.73 nmoles - g-1 - min-1, and 131 muM and 8.5 nmoles - g-1 - min-1, respectively). Hydrocortisone (28 muM) blocked the activity of the high affinity system without affecting the low affinity system. Apparently, there exists an extraneuronal compartment of high affinity that has a hydrocortisone-sensitive uptake mechnism; this compartment influences the concentration of catecholamines below the Km of this compartment. Supersensitivity ensues when either uptake or enzyme is blocked. Since the sensitivity effects of U-0521 and hydrocortisone are not additive, the high affinity compartment must a) metabolize most of the catecholamine transported into the compartment, and b) have a limited storage capacity for catecholamines after block of COMT."} {"id": "PMID:169169", "title": "[Studies on circadian rhythm and the feedback mechanism of hormone secretion from the hypothalamic-pituitary-adrenal system --pertaining to the circadian variation of feedback sensitivity in the hypothalamic-pituitary axis-- (author's transl)].", "content": "In order to investigate the relationship if any between the circadian rhythm of the hypothalamic-pituitary-adrenal system and of feedback sensitivity in the hypothalamic-pituitary axis, temporal changes of serum corticoid level and of ACTH responsiveness to metyrapone were studied in 5 controls, 4 patients with loss of consciousness due to central nervous system diseases (Group A), 2 blind subjects (Group B) and 2 patients with psychiatric disorders accompanied with sleep-wake cycle disturbance (Group C). Two patients in Group A with normal circadian rhythm of serum corticoid levels exhibited abnormal rhythm in ACTH responsiveness to metyrapone. In contrast, 2 other patients in Group A with normal rhythm in ACTH responsiveness to metyrapone exhibited abnormal circadian rhythms of serum corticoid levels. In spite of the disturbed circadian rhythm of serum corticoid levels, 2 patients in Group B showed normal rhythm in ACTH responsiveness to metyrapone. Two patients in Group C exhibited abnormalities in both circadian changes. It was concluded that there might be different control mechanisms between the circadian rhythmicity of the hypothalamic-pituitary-adrenal system and of the feedback sensitivity.", "contents": "[Studies on circadian rhythm and the feedback mechanism of hormone secretion from the hypothalamic-pituitary-adrenal system --pertaining to the circadian variation of feedback sensitivity in the hypothalamic-pituitary axis-- (author's transl)]. In order to investigate the relationship if any between the circadian rhythm of the hypothalamic-pituitary-adrenal system and of feedback sensitivity in the hypothalamic-pituitary axis, temporal changes of serum corticoid level and of ACTH responsiveness to metyrapone were studied in 5 controls, 4 patients with loss of consciousness due to central nervous system diseases (Group A), 2 blind subjects (Group B) and 2 patients with psychiatric disorders accompanied with sleep-wake cycle disturbance (Group C). Two patients in Group A with normal circadian rhythm of serum corticoid levels exhibited abnormal rhythm in ACTH responsiveness to metyrapone. In contrast, 2 other patients in Group A with normal rhythm in ACTH responsiveness to metyrapone exhibited abnormal circadian rhythms of serum corticoid levels. In spite of the disturbed circadian rhythm of serum corticoid levels, 2 patients in Group B showed normal rhythm in ACTH responsiveness to metyrapone. Two patients in Group C exhibited abnormalities in both circadian changes. It was concluded that there might be different control mechanisms between the circadian rhythmicity of the hypothalamic-pituitary-adrenal system and of the feedback sensitivity."} {"id": "PMID:169168", "title": "[Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)].", "content": "The present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin. Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds. Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs. Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response. It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas. Forty-eight hours after injection, the animals were completely diabetic. Light- and electron-microscopic exadminations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells. 1egenerative and necrotic changes were also seen in a few alpha-cells. These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight. Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT: 3g/kg). Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals. It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine. Pre-treatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective. N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity. It seems that streptozotocin interfers with NAD formation in the beta-cell. Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.).", "contents": "[Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)]. The present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin. Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds. Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs. Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response. It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas. Forty-eight hours after injection, the animals were completely diabetic. Light- and electron-microscopic exadminations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells. 1egenerative and necrotic changes were also seen in a few alpha-cells. These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight. Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT: 3g/kg). Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals. It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine. Pre-treatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective. N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity. It seems that streptozotocin interfers with NAD formation in the beta-cell. Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.)."} {"id": "PMID:169170", "title": "General dentistry and oral medicine in the hospital.", "content": "General dentistry in a hospital should not be confined to restorative dentistry happens to be performed in a hospital dental clinic. In addition to expertise in restorative dentistry and other dental specialties, general practitioners participating in hospital programs must also be students of two major areas-- diagnosis of diseases involving the head and neck as well as dental management of patients with severe medical disease. In the preceding short review a few examples of disorders about which the hospital dentist may be consulted were reviewed along with the proper protocol for requesting and answering consultations. This list is necessarily short and incomplete. A different group of disorders could have been discussed in this article. The competent hospital dentist must be a continual student of disease and its possible effect upon dental treatment and oral diagnosis. The task is formidable but rewarding and interesting.", "contents": "General dentistry and oral medicine in the hospital. General dentistry in a hospital should not be confined to restorative dentistry happens to be performed in a hospital dental clinic. In addition to expertise in restorative dentistry and other dental specialties, general practitioners participating in hospital programs must also be students of two major areas-- diagnosis of diseases involving the head and neck as well as dental management of patients with severe medical disease. In the preceding short review a few examples of disorders about which the hospital dentist may be consulted were reviewed along with the proper protocol for requesting and answering consultations. This list is necessarily short and incomplete. A different group of disorders could have been discussed in this article. The competent hospital dentist must be a continual student of disease and its possible effect upon dental treatment and oral diagnosis. The task is formidable but rewarding and interesting."} {"id": "PMID:169172", "title": "Hormonal regulation of incorporation of alanine-U-14C into glucose in human fetal liver explants. Effect of dibutyryl cyclic AMP, glucagon, insulin, and triamcinolone.", "content": "Incorporation of alanine-U-14C into glucose and liver glycogen increased linearly over sixty-five hours in culture of human fetal liver explants. This rate of incorporation was stimulated two- to tenfold by incubation with N6,2'O-dibutyryl adenosine 3'-5:cyclic monophosphate (dibutyryl cyclic AMP) (0.1 mM) plus theophylline (0.5 mM) or glucagon (7.5 mug./ml.) plus theophylline. No apparent lag period was detected, and the hormonal effect continued throughout the observation period. Insulin (1 U./ml.) significantly decreased both the basal rate of incorporation and the stimulated rate resulting from dibutyryl cyclic AMP or glucagon incubation. These effects were observed at both high (10mM) and low (2.8 mM) media glucose and from both 2.3 muM and 5 mM alanine-U-14C. Triamcinolone (20 mug./ml.) alone stimulated the rate of alanine-U-14C incorporation into glucose, whereas triamcinolone in the presence of dibutyryl cyclic AMP produced an increase in incorporation greater than the sum of the individual effects. The basal incorporation of alanine-U-14C into glucose by these human fetal liver explants provide a rate of approximately 4 nmoles glucose/gm. min, which is discussed in relation to the physiologic needs of the fetus and newborn.", "contents": "Hormonal regulation of incorporation of alanine-U-14C into glucose in human fetal liver explants. Effect of dibutyryl cyclic AMP, glucagon, insulin, and triamcinolone. Incorporation of alanine-U-14C into glucose and liver glycogen increased linearly over sixty-five hours in culture of human fetal liver explants. This rate of incorporation was stimulated two- to tenfold by incubation with N6,2'O-dibutyryl adenosine 3'-5:cyclic monophosphate (dibutyryl cyclic AMP) (0.1 mM) plus theophylline (0.5 mM) or glucagon (7.5 mug./ml.) plus theophylline. No apparent lag period was detected, and the hormonal effect continued throughout the observation period. Insulin (1 U./ml.) significantly decreased both the basal rate of incorporation and the stimulated rate resulting from dibutyryl cyclic AMP or glucagon incubation. These effects were observed at both high (10mM) and low (2.8 mM) media glucose and from both 2.3 muM and 5 mM alanine-U-14C. Triamcinolone (20 mug./ml.) alone stimulated the rate of alanine-U-14C incorporation into glucose, whereas triamcinolone in the presence of dibutyryl cyclic AMP produced an increase in incorporation greater than the sum of the individual effects. The basal incorporation of alanine-U-14C into glucose by these human fetal liver explants provide a rate of approximately 4 nmoles glucose/gm. min, which is discussed in relation to the physiologic needs of the fetus and newborn."} {"id": "PMID:169173", "title": "Insulin receptors in the heart muscle. Demonstration of specific binding sites and impairment of insulin binding in the plasma membrane of the obese hyperglycemic mouse.", "content": "The presence of insulin receptors in the heart muscle was investigated by measuring the binding of 125I-insulin to specific subcellular fractions of the rat and mouse myocardium. 125I-insulin bound to the plasma membrane fraction with a high degree of specificity and affinity. Insulin analogues competed with 125I-insulin in direct proportion to their biologic potency in vitro. Unlabeled insulin within the range of its concentrations in vivo inhibited 15 to 60 per cent of the 125I-insulin binding. The specific binding sites were finite in number and represented about 90 per cent of the total binding. The insulin-binding capacity of the plasma membrane fraction was twelve- to fifteenfold higher than that of the mitochondrial fraction. As in the liver, the binding was time- and temperature-dependent with a slower but higher binding achieved at a lower temperature. The binding sites appeared to be heterogeneous with respect to affinity. At 5 degrees C., the \"higher-affinity\" site had a K of about 2 times 10(9) M-1. No more than 10 per cent of the 125I-insulin was degraded by the heart plasma membranes after one hour at 30 degrees C. or twenty-two hours at 5 degrees C. Studies in the obese hyperglycemic (ob/ob) mouse revealed that the insulin binding is impaired in the heart muscle of this animal. Over a wide range of insulin concentrations, the plasma membrane fraction of ob/ob mice bound only 25 to 40 per cent as much insulin as did membranes of the thin littermates, suggesting that, as in the liver, the fat tissue, and the thymic lymphocyte, the number of insulin-binding sites is decreased in the heart of the ob/ob mouse. This defect selectively affected the plasma membrane fraction and could not be explained by differences in membrane purification or insulin-degrading activity. Heart and liver membranes of forty-hour fasted ob/ob mice bound two to three times as much insulin as did membranes of ob/ob mice fed ad libitum. These studies demonstrate and characterize the binding of insulin to heart muscle membranes; they extend to the heart muscle the insulin receptor defect also found in liver membranes and cells, in fat cell membranes, and in thymic lymphocytes of the ob/ob mouse.", "contents": "Insulin receptors in the heart muscle. Demonstration of specific binding sites and impairment of insulin binding in the plasma membrane of the obese hyperglycemic mouse. The presence of insulin receptors in the heart muscle was investigated by measuring the binding of 125I-insulin to specific subcellular fractions of the rat and mouse myocardium. 125I-insulin bound to the plasma membrane fraction with a high degree of specificity and affinity. Insulin analogues competed with 125I-insulin in direct proportion to their biologic potency in vitro. Unlabeled insulin within the range of its concentrations in vivo inhibited 15 to 60 per cent of the 125I-insulin binding. The specific binding sites were finite in number and represented about 90 per cent of the total binding. The insulin-binding capacity of the plasma membrane fraction was twelve- to fifteenfold higher than that of the mitochondrial fraction. As in the liver, the binding was time- and temperature-dependent with a slower but higher binding achieved at a lower temperature. The binding sites appeared to be heterogeneous with respect to affinity. At 5 degrees C., the \"higher-affinity\" site had a K of about 2 times 10(9) M-1. No more than 10 per cent of the 125I-insulin was degraded by the heart plasma membranes after one hour at 30 degrees C. or twenty-two hours at 5 degrees C. Studies in the obese hyperglycemic (ob/ob) mouse revealed that the insulin binding is impaired in the heart muscle of this animal. Over a wide range of insulin concentrations, the plasma membrane fraction of ob/ob mice bound only 25 to 40 per cent as much insulin as did membranes of the thin littermates, suggesting that, as in the liver, the fat tissue, and the thymic lymphocyte, the number of insulin-binding sites is decreased in the heart of the ob/ob mouse. This defect selectively affected the plasma membrane fraction and could not be explained by differences in membrane purification or insulin-degrading activity. Heart and liver membranes of forty-hour fasted ob/ob mice bound two to three times as much insulin as did membranes of ob/ob mice fed ad libitum. These studies demonstrate and characterize the binding of insulin to heart muscle membranes; they extend to the heart muscle the insulin receptor defect also found in liver membranes and cells, in fat cell membranes, and in thymic lymphocytes of the ob/ob mouse."} {"id": "PMID:169174", "title": "Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats.", "content": "The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development.", "contents": "Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats. The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development."} {"id": "PMID:169175", "title": "Comparison of 125-I-insulin binding and degradation to isolated rat hepatocytes and liver membranes.", "content": "We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by collagenase digestion of extracellular matric. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 times 10(6) cells per milliliter) and membranes (150 mug. protein per milliliter) that gave equal binding at insulin concentrations less than 100 ng./ml., the amount of insulin specifically bound at insulin concentrations greater than 100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 per cent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists; which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 times 10(-7) M at 37 degrees) was the same for both systems wereas the Vmax was greater with use of hepatocytes. (1) Preparation of hepatocytes by collagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations less than 100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon.", "contents": "Comparison of 125-I-insulin binding and degradation to isolated rat hepatocytes and liver membranes. We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by collagenase digestion of extracellular matric. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 times 10(6) cells per milliliter) and membranes (150 mug. protein per milliliter) that gave equal binding at insulin concentrations less than 100 ng./ml., the amount of insulin specifically bound at insulin concentrations greater than 100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 per cent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists; which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 times 10(-7) M at 37 degrees) was the same for both systems wereas the Vmax was greater with use of hepatocytes. (1) Preparation of hepatocytes by collagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations less than 100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon."} {"id": "PMID:169177", "title": "Infantile polyneuropathy with defective myelination: an autopsy study.", "content": "A case is reported of a boy who developed a severe polyneuropathy in early infancy and died of respiratory failure at the age of 18 months. Autopsy revealed almost total lack of myelin sheaths in the cranial, spinal and peripheral nerves. The defect involved the entire peripheral nervous system and was confined to it, central myelination being normal. It is suggested that this case is another example of the condition described by Lyon (1969) and by Kennedy et al. (1971) in which pathological observations were confined to biopsy material. In spite of some similarities between these cases and those of hypertrophic neuropathy reported by D\u00e9jerine and Sottas in 1893, they seem to form a distinct sub-group, possibly even a separate entity: infantile polyneuropathy with defective myelination.", "contents": "Infantile polyneuropathy with defective myelination: an autopsy study. A case is reported of a boy who developed a severe polyneuropathy in early infancy and died of respiratory failure at the age of 18 months. Autopsy revealed almost total lack of myelin sheaths in the cranial, spinal and peripheral nerves. The defect involved the entire peripheral nervous system and was confined to it, central myelination being normal. It is suggested that this case is another example of the condition described by Lyon (1969) and by Kennedy et al. (1971) in which pathological observations were confined to biopsy material. In spite of some similarities between these cases and those of hypertrophic neuropathy reported by D\u00e9jerine and Sottas in 1893, they seem to form a distinct sub-group, possibly even a separate entity: infantile polyneuropathy with defective myelination."} {"id": "PMID:169176", "title": "Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep.", "content": "To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones.", "contents": "Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones."} {"id": "PMID:169179", "title": "On the pathogenesis of duchenne muscular dystrophy.", "content": "The relative merits of the three presently most active hypotheses (vascular, neurogenic, and myogenic) concerning the pathogenesis of Duchenne muscular dystrophy are analysed and discussed and the literature is comprehensively reviewed.", "contents": "On the pathogenesis of duchenne muscular dystrophy. The relative merits of the three presently most active hypotheses (vascular, neurogenic, and myogenic) concerning the pathogenesis of Duchenne muscular dystrophy are analysed and discussed and the literature is comprehensively reviewed."} {"id": "PMID:169180", "title": "Aldolase isoenzymes in liver cirrhosis and primary liver cell cancer.", "content": "The isoenzymatic pattern of aldolase was determined by immunoprecipitation with specific anti-aldolase A, B and C sera in 21 pathological liver tissues and in the sera of normals (n equals 20), liver cirrhotics (n equals 52) and hepatoma patients (n equals 22). The increase of aldolase A in primary liver cell carcinoma is not reflected in the sera of these patients, cannot be used for diagnostic purposes and is not hepatoma-specific.", "contents": "Aldolase isoenzymes in liver cirrhosis and primary liver cell cancer. The isoenzymatic pattern of aldolase was determined by immunoprecipitation with specific anti-aldolase A, B and C sera in 21 pathological liver tissues and in the sera of normals (n equals 20), liver cirrhotics (n equals 52) and hepatoma patients (n equals 22). The increase of aldolase A in primary liver cell carcinoma is not reflected in the sera of these patients, cannot be used for diagnostic purposes and is not hepatoma-specific."} {"id": "PMID:169181", "title": "Transplantation immunity of rats induced by hepatoma cells treated with heteroantibody.", "content": "Tumor cells from rat hepatomas, AH-414 and AH-64A induced by azo dye, were preincubated in vitro with different dilutions of rabbit anti-hepatoma serum. Then 10(6) cells were inoculated intraperitoneally into Donryu rats. After 6 weeks, rats surviving without tumors showed resistance to further challenge with the same tumor cells. The ratio of the number of surviving rats after challenge with 10(5) fresh tumor cells to those surviving after inoculation with serum-treated tumor cells was maximal using dilutions of antiserum of 1:240 with AH-414 tumor cells and of 1:400 with AH-64A cells. Pooled sera from AH-64A-resistant rats, 2 weeks after a 3rd challenge with 10(7) fresh tumor cells (RRS Lot III), had a cytotoxic effect on AH-64A cells at dilutions of up to 1:64 while sera isolated after the 1st or 2nd challenge (RRS Lot I or II) were weakly cytotoxic. The cytotoxicity was complement-dependent and stable on heating at 56 degrees for 30 min. RRS Lot III was active in the indirect immunofluorescence test. Rabbit anti-rat liver serum did not induce resistance to AH-64A in Donryu rats although the dilutions used had the same immune adherence or cytotoxic titer as rabbit anti-hepatoma serum. Rabbit anti-Donryu rat hepatoma serum failed to induce resistance to cells of a 3-methylcholanthrene-induced sarcoma, AMC 60, of ACI/N rats. The correlation between the immune adherence and cytotoxic titers of the rabbit antiserum and its effectiveness in sensitizing the animals against tumor cells is discussed.", "contents": "Transplantation immunity of rats induced by hepatoma cells treated with heteroantibody. Tumor cells from rat hepatomas, AH-414 and AH-64A induced by azo dye, were preincubated in vitro with different dilutions of rabbit anti-hepatoma serum. Then 10(6) cells were inoculated intraperitoneally into Donryu rats. After 6 weeks, rats surviving without tumors showed resistance to further challenge with the same tumor cells. The ratio of the number of surviving rats after challenge with 10(5) fresh tumor cells to those surviving after inoculation with serum-treated tumor cells was maximal using dilutions of antiserum of 1:240 with AH-414 tumor cells and of 1:400 with AH-64A cells. Pooled sera from AH-64A-resistant rats, 2 weeks after a 3rd challenge with 10(7) fresh tumor cells (RRS Lot III), had a cytotoxic effect on AH-64A cells at dilutions of up to 1:64 while sera isolated after the 1st or 2nd challenge (RRS Lot I or II) were weakly cytotoxic. The cytotoxicity was complement-dependent and stable on heating at 56 degrees for 30 min. RRS Lot III was active in the indirect immunofluorescence test. Rabbit anti-rat liver serum did not induce resistance to AH-64A in Donryu rats although the dilutions used had the same immune adherence or cytotoxic titer as rabbit anti-hepatoma serum. Rabbit anti-Donryu rat hepatoma serum failed to induce resistance to cells of a 3-methylcholanthrene-induced sarcoma, AMC 60, of ACI/N rats. The correlation between the immune adherence and cytotoxic titers of the rabbit antiserum and its effectiveness in sensitizing the animals against tumor cells is discussed."} {"id": "PMID:169182", "title": "The effect of age on mitochondrial enzymes and respiration.", "content": "There was no significant difference between the levels of cytochrome oxidase and malate dehydrogenase in whole liver homogenates or in mitochondria isolated from the livers of 6-month-old and 30-month-old C57/BL mice. Little change with age was found in the cytochemical localisation of either enzyme. There were no significant changes in endogenous, state III or state IV respiration of mitochondria isolated from the livers of young and old mice.", "contents": "The effect of age on mitochondrial enzymes and respiration. There was no significant difference between the levels of cytochrome oxidase and malate dehydrogenase in whole liver homogenates or in mitochondria isolated from the livers of 6-month-old and 30-month-old C57/BL mice. Little change with age was found in the cytochemical localisation of either enzyme. There were no significant changes in endogenous, state III or state IV respiration of mitochondria isolated from the livers of young and old mice."} {"id": "PMID:169183", "title": "Nonlanguage disorders of speech reflect complex neurologic apparatus.", "content": "The mute or nearly mute patient who is alert and has good understanding of speech and a right hemiparesis could have Broca's aphasia, akinesia of speech (transcortical motor aphasia), or aphemia. The patient who has Broca's aphasia does not write well, and his speech does not improve greatly with repetition. The speech of a patient with akinesia of speech improves with repetition. The aphemic patient writes normally, but his speech does not improve with repetition. The mute patient whose eyes are open but who is poorly responsive and moves little or not at all could be an akinetic mute (with either a cingulate or a thalamomesencephalic lesion) or have a locked-in syndrome. The latter is diagnosed by asking the patient to look up and down or to open and close his eyes. If he obeys these commands, the physician questions him using a code of eye movement responses. If the patient fails to respond at all, he is an akinetic mute; intense stimulation may result in speech or movement. If the patient is drowsy and has third nerve involvement, the lesion is in the thalamomesencephalic reticular formation. If the patient appears alert and has episodes of agitation, he probably has bilateral lesions in the gyri cinguli. Patients with weakness of the bulbar musculature (facial, palatal, and tongue weakness and dysphonia) may have either upper motor neuron or lower motor neuron lesions. Only bilateral upper motor neuron lesions produce permanent dysarthria. As a typical example, a patient has a transient left hemiparesis with dysarthria and almost completely recovers. Later, however, a right hemiparesis develops and the patient experiences severe bilateral facial weakness, drooling, dysphagia, and severe dysarthria. The absence of atrophy of the bulbar musculature, a hyperactive jaw jerk and gag reflex and, sometimes, inappropriate laughing or crying episodes indicate that the lesion is located above the medulla in the corticobulbar tracts. Flaccid paralysis, absence of the jaw jerk or gag reflex, and absence of other upper motor neuron signs, such as upgoing toes, indicate a lower motor neuron or neuromuscular junction problem. Appropriate tests to rule out myasthenia gravis should be done. The other conditions discussed here are often obvious from their clinical presentation. Although the specific disorder of speech sometimes is helpful in localizing the cause, in most patients, the associated deficits on neurologic examination are of greatest value.", "contents": "Nonlanguage disorders of speech reflect complex neurologic apparatus. The mute or nearly mute patient who is alert and has good understanding of speech and a right hemiparesis could have Broca's aphasia, akinesia of speech (transcortical motor aphasia), or aphemia. The patient who has Broca's aphasia does not write well, and his speech does not improve greatly with repetition. The speech of a patient with akinesia of speech improves with repetition. The aphemic patient writes normally, but his speech does not improve with repetition. The mute patient whose eyes are open but who is poorly responsive and moves little or not at all could be an akinetic mute (with either a cingulate or a thalamomesencephalic lesion) or have a locked-in syndrome. The latter is diagnosed by asking the patient to look up and down or to open and close his eyes. If he obeys these commands, the physician questions him using a code of eye movement responses. If the patient fails to respond at all, he is an akinetic mute; intense stimulation may result in speech or movement. If the patient is drowsy and has third nerve involvement, the lesion is in the thalamomesencephalic reticular formation. If the patient appears alert and has episodes of agitation, he probably has bilateral lesions in the gyri cinguli. Patients with weakness of the bulbar musculature (facial, palatal, and tongue weakness and dysphonia) may have either upper motor neuron or lower motor neuron lesions. Only bilateral upper motor neuron lesions produce permanent dysarthria. As a typical example, a patient has a transient left hemiparesis with dysarthria and almost completely recovers. Later, however, a right hemiparesis develops and the patient experiences severe bilateral facial weakness, drooling, dysphagia, and severe dysarthria. The absence of atrophy of the bulbar musculature, a hyperactive jaw jerk and gag reflex and, sometimes, inappropriate laughing or crying episodes indicate that the lesion is located above the medulla in the corticobulbar tracts. Flaccid paralysis, absence of the jaw jerk or gag reflex, and absence of other upper motor neuron signs, such as upgoing toes, indicate a lower motor neuron or neuromuscular junction problem. Appropriate tests to rule out myasthenia gravis should be done. The other conditions discussed here are often obvious from their clinical presentation. Although the specific disorder of speech sometimes is helpful in localizing the cause, in most patients, the associated deficits on neurologic examination are of greatest value."} {"id": "PMID:169189", "title": "[Effect of [ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation and fibrinolysis activity].", "content": "Inibitory effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation (in vitro and in vivo) and the fibrinolytic activity (in vivo) were examined and compared with otherinhibitors. Inhibitory effect on kinin forming activity (in vitro) of various enzymes was measured in the guinea pig ileum. FOY and Trasylol inhibited the kinin forming activities of trypsin, pancreas kallikrein and plasma kallikrein. Soybean trypsin inhibitor inhibited kinin like substance was formed in the perfusate when the rat's paw was heated at 46 degrees C. FOY and T-asylol added to the perfusion fluid produced a potent inhibition of the formation of bradykinin-like substance. When administered i.v., FOY and Trasylol did not inhibit the formation of bradykinin-like substance. In the dog, activation of plasmin in the circulatory blood and increase of hemorrhagic tendency were caused by the i.v. administration of human serum plus streptokinase. Such responses were inhibited with a previous i.v. infusion of FOY and t-AMCHA. From the above findings, it may be concluded that FOY has inhibitory effects on kinin formation and fibrinolytic activity.", "contents": "[Effect of [ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation and fibrinolysis activity]. Inibitory effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation (in vitro and in vivo) and the fibrinolytic activity (in vivo) were examined and compared with otherinhibitors. Inhibitory effect on kinin forming activity (in vitro) of various enzymes was measured in the guinea pig ileum. FOY and Trasylol inhibited the kinin forming activities of trypsin, pancreas kallikrein and plasma kallikrein. Soybean trypsin inhibitor inhibited kinin like substance was formed in the perfusate when the rat's paw was heated at 46 degrees C. FOY and T-asylol added to the perfusion fluid produced a potent inhibition of the formation of bradykinin-like substance. When administered i.v., FOY and Trasylol did not inhibit the formation of bradykinin-like substance. In the dog, activation of plasmin in the circulatory blood and increase of hemorrhagic tendency were caused by the i.v. administration of human serum plus streptokinase. Such responses were inhibited with a previous i.v. infusion of FOY and t-AMCHA. From the above findings, it may be concluded that FOY has inhibitory effects on kinin formation and fibrinolytic activity."} {"id": "PMID:169190", "title": "Differential effects of chlorpromazine, imipramine, nitrazepam and amobarbital on REM sleep and REM density in man.", "content": "The effect of chlorpromazine (CPZ), imipramine (IMP), nitrazepam (NZP) and amobarbital sodium (AMOB) on the REM period of sleep (REMP) was investigated on four subjects by means of all-night sleep polygraphy with the schedule PPPDDDPP where P is placebo and D active drug. CPZ 25 mg resulted in a slight increase in %REMP, and no significant change in REM density (1 second fraction method) and total REM activity during the drug and withdrawal nights. IMP 25 mg produced moderate decrease in %REMP in the three drug nights, whereas REM density decreased only in the first drug night. NZP 5 mg resulted in a slight parallel suppression of %REMP, REM density and total REM activity during the drug nights. AMOB 200 mg produced a slight decrease in %REMP and marked decrease in REM density during the drug nights. Rebound increase of %REMP and a tendency of carry over decrease of REM density were observed in the withdrawal nights. Decrease in the REM density was more marked in AMOB than in NZP drug night. The importance of the simultaneous analysis of %REMP and REM density for the study of effects of psychotrophic drugs on sleep was emphasized.", "contents": "Differential effects of chlorpromazine, imipramine, nitrazepam and amobarbital on REM sleep and REM density in man. The effect of chlorpromazine (CPZ), imipramine (IMP), nitrazepam (NZP) and amobarbital sodium (AMOB) on the REM period of sleep (REMP) was investigated on four subjects by means of all-night sleep polygraphy with the schedule PPPDDDPP where P is placebo and D active drug. CPZ 25 mg resulted in a slight increase in %REMP, and no significant change in REM density (1 second fraction method) and total REM activity during the drug and withdrawal nights. IMP 25 mg produced moderate decrease in %REMP in the three drug nights, whereas REM density decreased only in the first drug night. NZP 5 mg resulted in a slight parallel suppression of %REMP, REM density and total REM activity during the drug nights. AMOB 200 mg produced a slight decrease in %REMP and marked decrease in REM density during the drug nights. Rebound increase of %REMP and a tendency of carry over decrease of REM density were observed in the withdrawal nights. Decrease in the REM density was more marked in AMOB than in NZP drug night. The importance of the simultaneous analysis of %REMP and REM density for the study of effects of psychotrophic drugs on sleep was emphasized."} {"id": "PMID:169193", "title": "[The angiographic findings in focal nodular hyperplasia of the liver(author's transl)].", "content": "Four cases of FNH are described; the angiographic appearances are detailed and problems in differential diagnosis are discussed. FNH presents as a hypervascular benign space-occupying process in the liver, with a typical vascular structure and intensive prolonged and sharply demarcated parenchymal staining. It can be distinguished from malignant lesions in the liver by the absence of tumour vessels, infiltration and occlusion of vessels.", "contents": "[The angiographic findings in focal nodular hyperplasia of the liver(author's transl)]. Four cases of FNH are described; the angiographic appearances are detailed and problems in differential diagnosis are discussed. FNH presents as a hypervascular benign space-occupying process in the liver, with a typical vascular structure and intensive prolonged and sharply demarcated parenchymal staining. It can be distinguished from malignant lesions in the liver by the absence of tumour vessels, infiltration and occlusion of vessels."} {"id": "PMID:169194", "title": "[The clinical features and diagnosis of glomus tumours (author's transl)].", "content": "The symptoms of chemodectomas are described briefly and the literature reviewed. Two cases are presented; of these, one was a typical glomus jugulare tumour, the other an unusual metastasising glomus tumour. The role of radiological diagnosis is discussed and the value of angiography is stressed. Some suggestions regarding treatment are also made.", "contents": "[The clinical features and diagnosis of glomus tumours (author's transl)]. The symptoms of chemodectomas are described briefly and the literature reviewed. Two cases are presented; of these, one was a typical glomus jugulare tumour, the other an unusual metastasising glomus tumour. The role of radiological diagnosis is discussed and the value of angiography is stressed. Some suggestions regarding treatment are also made."} {"id": "PMID:169195", "title": "[Out-patient treatment and prognosis schizophrenic patients after first hospitalization (author's transl)].", "content": "99 schizophrenic patients from the General Mental Hospital in G\u00f6ttingen who had received hospital treatment for the first time, where, after their discharge from hospital, studied for a period of 1 1/2 to 4 1/2 years. Information was collected with regard to the further progress of the disease on the one hand, and the response to drugs used in treatment on the other. Less than half the patients who had suffered from the disease from several years without receiving any out-patient treatment could not be helped or cured by the following hospital treatment. Over half of them had to be readmitted to hospital at last once (mostly within one year). A persisting or newly developing illness could be ascertained by catamnestic means in about 2/3 of the patients. The post-hospital treatment was left predominantly to the GP. Psycho-social help was generally lacking. Drugs were used regulary as far as could be ascertained in only 1/5 of the patients. In most cases the after-care was stopped after several months. This data shows that the treatment before, during and after hospitalization was in many cases inadequate. For different reasons the therapeutical possibilities hat not been used to their full extent. Due to the strict separation between the out-patient and hospital therapy the schizophrenic patients received treatment too late, for too short a time, and not suited usually to their individual needs.", "contents": "[Out-patient treatment and prognosis schizophrenic patients after first hospitalization (author's transl)]. 99 schizophrenic patients from the General Mental Hospital in G\u00f6ttingen who had received hospital treatment for the first time, where, after their discharge from hospital, studied for a period of 1 1/2 to 4 1/2 years. Information was collected with regard to the further progress of the disease on the one hand, and the response to drugs used in treatment on the other. Less than half the patients who had suffered from the disease from several years without receiving any out-patient treatment could not be helped or cured by the following hospital treatment. Over half of them had to be readmitted to hospital at last once (mostly within one year). A persisting or newly developing illness could be ascertained by catamnestic means in about 2/3 of the patients. The post-hospital treatment was left predominantly to the GP. Psycho-social help was generally lacking. Drugs were used regulary as far as could be ascertained in only 1/5 of the patients. In most cases the after-care was stopped after several months. This data shows that the treatment before, during and after hospitalization was in many cases inadequate. For different reasons the therapeutical possibilities hat not been used to their full extent. Due to the strict separation between the out-patient and hospital therapy the schizophrenic patients received treatment too late, for too short a time, and not suited usually to their individual needs."} {"id": "PMID:169197", "title": "Effects of adenosine 3':5'-cyclic monophosphate and guanosine 3':5'-cyclic monophosphate on 3H-uridine incorporation into glomerulosal cells of hypophysectomized rat adrenal cortex.", "content": "The effects of cyclic AMP and cyclic GMP on the incorporation of 3H-uridine into glomerulosal cells of hypophysectomized rats were investigated by high resolution autoradiography. The quantitative analysis of autoradiographs shows that cyclic nucleotides, like ACTH, enhance the tracer incorporation into both nuclear and mitochondrial compartments. These findings are discussed in relation to previous results indicating that both cyclic nucleotides function as intracellular mediators of the trophic action of ACTH on the rat adrenal zona glomerulosa. The hypothesis that the mechanism of the glomerulotrophic action of ACTH and cyclic nucleotides involves the stimulation of nuclear and mitochondrial RNA synthesis is discussed.", "contents": "Effects of adenosine 3':5'-cyclic monophosphate and guanosine 3':5'-cyclic monophosphate on 3H-uridine incorporation into glomerulosal cells of hypophysectomized rat adrenal cortex. The effects of cyclic AMP and cyclic GMP on the incorporation of 3H-uridine into glomerulosal cells of hypophysectomized rats were investigated by high resolution autoradiography. The quantitative analysis of autoradiographs shows that cyclic nucleotides, like ACTH, enhance the tracer incorporation into both nuclear and mitochondrial compartments. These findings are discussed in relation to previous results indicating that both cyclic nucleotides function as intracellular mediators of the trophic action of ACTH on the rat adrenal zona glomerulosa. The hypothesis that the mechanism of the glomerulotrophic action of ACTH and cyclic nucleotides involves the stimulation of nuclear and mitochondrial RNA synthesis is discussed."} {"id": "PMID:169198", "title": "The differential effect of cholera toxin on the lymphocyte stimulation induced by various mitogens.", "content": "BALB/c spleen cells (5 x 10(6)) were cultured in 1 ml of serum-free RPMI 1640 medium for 3 days in order to examine the effect of cholera enterotoxin (CN) and its spontaneously formed toxoid (CD) on lymphocyte stimulation. Stimulation was assessed after addition of [3H] thymidine for the last 16 hours of culture. One microgram of CN per culture markedly reduced the baseline of [3H] thymidine incorporation and the stimulation due to phytohaemagglutinin (PHA), concanavalin A (con A) and bacterial lipopolysaccharide (LPS). One microgram of CD diminished the base-line to half, abolished the response to PHA, reduced the response to con A and had very little effect on the LPS-induced stimulation. One-tenth the amount (0-1 mug) of both CN and CD affected only the PHA reaction. A secondary response to haemocyanin in vitro was not decreased by this lower dose. The effect of 1 mug on CN on the LPS response could be reduced by pretreatment of the cells with CD, whereas the PHA reaction remained markedly diminished. Dibutyryl-cAMP added to culture tubes had a similar effect ot 1 mug of CN, affecting the PHA response much more than the response to LPS. Spleen cells of mice immunized with CD gave a significant proliferative response to both 1 mug of CD and CN. The results are interpreted as indicating a strong inhibitory effect of CN mediated by accumulation of intracellular cAMP. CD-immunized cells contain specific receptors for both CD and CN which probably compete with the sites responsible for adenylate cyclase stimulation by CN.", "contents": "The differential effect of cholera toxin on the lymphocyte stimulation induced by various mitogens. BALB/c spleen cells (5 x 10(6)) were cultured in 1 ml of serum-free RPMI 1640 medium for 3 days in order to examine the effect of cholera enterotoxin (CN) and its spontaneously formed toxoid (CD) on lymphocyte stimulation. Stimulation was assessed after addition of [3H] thymidine for the last 16 hours of culture. One microgram of CN per culture markedly reduced the baseline of [3H] thymidine incorporation and the stimulation due to phytohaemagglutinin (PHA), concanavalin A (con A) and bacterial lipopolysaccharide (LPS). One microgram of CD diminished the base-line to half, abolished the response to PHA, reduced the response to con A and had very little effect on the LPS-induced stimulation. One-tenth the amount (0-1 mug) of both CN and CD affected only the PHA reaction. A secondary response to haemocyanin in vitro was not decreased by this lower dose. The effect of 1 mug on CN on the LPS response could be reduced by pretreatment of the cells with CD, whereas the PHA reaction remained markedly diminished. Dibutyryl-cAMP added to culture tubes had a similar effect ot 1 mug of CN, affecting the PHA response much more than the response to LPS. Spleen cells of mice immunized with CD gave a significant proliferative response to both 1 mug of CD and CN. The results are interpreted as indicating a strong inhibitory effect of CN mediated by accumulation of intracellular cAMP. CD-immunized cells contain specific receptors for both CD and CN which probably compete with the sites responsible for adenylate cyclase stimulation by CN."} {"id": "PMID:169201", "title": "Sensitive assay for detection of toxin-induced damage to the cytoplasmic membrane of human diploid fibroblasts.", "content": "A sensitive assay was developed for detection and quantitation of subtle permeability changes in the cytoplasmic membrane of human diploid fibroblasts. Release of the non-metabolizable amino acid [1-14C]alpha-aminoisobutyric acid (AIB; molecular weight (103) from the cytoplasm of prelabeled cells was used as an indicator of toxin-induced membrane damage. An optimal procedure for labeling these cells was designed after varying the conditions with regard to pH, temperature, concentration of AIB, composition of medium, and incubation time. Toxin-induced release of AIB was compared with release of a previously described nucleotide label, [3H]uridine. Melittin from bee venom and the polyene antibiotics filipin and amphotericin B in low concentrations induced a strikingly greater release of AIB than of nucleotide label. The sensitivity of this assay was furthermore demonstrated by treatment with the following bacterial cytolysins: phospholipase C and theta-toxin from Clostridium perfringens, alpha-, beta-, delta-, and gamma-toxins from Staphylococcus aureus, and streptolysin S from Streptococcus pyogenes. In spite of their different modes of action, all these membrane-active toxins at low concentrations induced a significant release of AIB label. For an equal release of nucleotide label, several times higher concentrations were required.", "contents": "Sensitive assay for detection of toxin-induced damage to the cytoplasmic membrane of human diploid fibroblasts. A sensitive assay was developed for detection and quantitation of subtle permeability changes in the cytoplasmic membrane of human diploid fibroblasts. Release of the non-metabolizable amino acid [1-14C]alpha-aminoisobutyric acid (AIB; molecular weight (103) from the cytoplasm of prelabeled cells was used as an indicator of toxin-induced membrane damage. An optimal procedure for labeling these cells was designed after varying the conditions with regard to pH, temperature, concentration of AIB, composition of medium, and incubation time. Toxin-induced release of AIB was compared with release of a previously described nucleotide label, [3H]uridine. Melittin from bee venom and the polyene antibiotics filipin and amphotericin B in low concentrations induced a strikingly greater release of AIB than of nucleotide label. The sensitivity of this assay was furthermore demonstrated by treatment with the following bacterial cytolysins: phospholipase C and theta-toxin from Clostridium perfringens, alpha-, beta-, delta-, and gamma-toxins from Staphylococcus aureus, and streptolysin S from Streptococcus pyogenes. In spite of their different modes of action, all these membrane-active toxins at low concentrations induced a significant release of AIB label. For an equal release of nucleotide label, several times higher concentrations were required."} {"id": "PMID:169202", "title": "Rabbit corneal damage produced by Pseudomonas aeruginosa infection.", "content": "Gross, light microscopic, and electron microscopic examination of the rabbit corneal destruction produced by experimental Pseudomonas aeruginosa infections revealed a combination of acute inflammation and liquefaction necrosis of the cornea. Degeneration of the epithelial cells and the start of polymorphonuclear leukocyte infiltration of the cornea occurred initially. These changes were followed by loss of the epithelium, degeneration and loss of the keratocytes and endothelium, loss of the characteristic weblike pattern of the proteoglycan ground substance, dispersal of ultrastructurally normal collagen fibrils, extensive accumulation followed by degeneration of polymorphonuclear leukocytes, and accumulation of plasma proteins and fibrin in the necrotic cornea. Histochemical examination of the cornea suggested a loss of the proteoglycan ground substance but not of collagen. Rabbit corneas injected with Clostridium histolyticum collagenase showed gross and cellular changes similar to those observed during the pseudomonal infections; however, histochemical examination suggested a loss of collagen, and electron microscopy revealed ultrastructurally abnormal collagen fibrils. The results support the idea (i) that a bacterial or host-derived collagenase is not required for extensive corneal damage during a P. aeruginosa corneal infection, and (ii) that a P. aeruginosa corneal infection may severly damage the cornea by producing extensive corneal edema and by causing the loss of the corneal proteoglycan ground substance, thus resulting in dispersal of undamaged collagen fibrils, weakening of the cornea, and subsequent descemetocele formation and corneal perforation by the anterior chamber pressure.", "contents": "Rabbit corneal damage produced by Pseudomonas aeruginosa infection. Gross, light microscopic, and electron microscopic examination of the rabbit corneal destruction produced by experimental Pseudomonas aeruginosa infections revealed a combination of acute inflammation and liquefaction necrosis of the cornea. Degeneration of the epithelial cells and the start of polymorphonuclear leukocyte infiltration of the cornea occurred initially. These changes were followed by loss of the epithelium, degeneration and loss of the keratocytes and endothelium, loss of the characteristic weblike pattern of the proteoglycan ground substance, dispersal of ultrastructurally normal collagen fibrils, extensive accumulation followed by degeneration of polymorphonuclear leukocytes, and accumulation of plasma proteins and fibrin in the necrotic cornea. Histochemical examination of the cornea suggested a loss of the proteoglycan ground substance but not of collagen. Rabbit corneas injected with Clostridium histolyticum collagenase showed gross and cellular changes similar to those observed during the pseudomonal infections; however, histochemical examination suggested a loss of collagen, and electron microscopy revealed ultrastructurally abnormal collagen fibrils. The results support the idea (i) that a bacterial or host-derived collagenase is not required for extensive corneal damage during a P. aeruginosa corneal infection, and (ii) that a P. aeruginosa corneal infection may severly damage the cornea by producing extensive corneal edema and by causing the loss of the corneal proteoglycan ground substance, thus resulting in dispersal of undamaged collagen fibrils, weakening of the cornea, and subsequent descemetocele formation and corneal perforation by the anterior chamber pressure."} {"id": "PMID:169203", "title": "Hormonal regulation of drug metabolism during pregnancy.", "content": "During pregnancy, a significant change has been found in the pattern of liver response to drugs. The activity of drug-metabolizing enzymes was inhibited due to the presence of increased amounts of reduced progesterone metabolites produced by the pregnant animal. Treatment of non-pregnant rats with 5alpha-pregnan-3beta-ol-20-one or 5alpha-pregnan-3beta,20beta-diol also caused a decreased drug hydroxylation. On the other hand, the administration of 16alpha-hydroxyprogesterone resulted in an increased activity. The contrasting effects of the different steroids on the function of the endoplasmic reticulum have shown correlation with changes in microsomal phospholipid synthesis. Reduced progesterone derivatives brought about a decrease, whereas hydroxyprogesterone an enhancement. The opposite actions provided evidence to postulate that during pregnancy the formation of endoplasmic reticulum and associated induction processes of drug metabolism might be regulated by a balance displayed in the production of various progesterone metabolites.", "contents": "Hormonal regulation of drug metabolism during pregnancy. During pregnancy, a significant change has been found in the pattern of liver response to drugs. The activity of drug-metabolizing enzymes was inhibited due to the presence of increased amounts of reduced progesterone metabolites produced by the pregnant animal. Treatment of non-pregnant rats with 5alpha-pregnan-3beta-ol-20-one or 5alpha-pregnan-3beta,20beta-diol also caused a decreased drug hydroxylation. On the other hand, the administration of 16alpha-hydroxyprogesterone resulted in an increased activity. The contrasting effects of the different steroids on the function of the endoplasmic reticulum have shown correlation with changes in microsomal phospholipid synthesis. Reduced progesterone derivatives brought about a decrease, whereas hydroxyprogesterone an enhancement. The opposite actions provided evidence to postulate that during pregnancy the formation of endoplasmic reticulum and associated induction processes of drug metabolism might be regulated by a balance displayed in the production of various progesterone metabolites."} {"id": "PMID:169200", "title": "Studies on the action of hormones on the intestinal transport of L-histidine.", "content": "Intestinal absorption of L-histidine as affected by insulin, diabetes, hydrocortisone, adrenocorticotrophic hormone (ACTH) and thyroxine has been studied. Intestinal absorption of L-histidine is not significantly increased following insulin administration. Similarly, addition of insulin in vitro did not change the transport activity significantly. When rats are made diabetic on administration of alloxan monohydrate, the transport activity is increased. Hydrocortisone, adrenocorticotrophic hormone and thyroxine treatment increased the absorption of L-histidine by small intestine. However, addition in vitro of ACTH and hydrocortisone did not change the absorption of L-histidines by small intestine. It appears that the facilitative action of these hormones is not due to their direct action of the membrane.", "contents": "Studies on the action of hormones on the intestinal transport of L-histidine. Intestinal absorption of L-histidine as affected by insulin, diabetes, hydrocortisone, adrenocorticotrophic hormone (ACTH) and thyroxine has been studied. Intestinal absorption of L-histidine is not significantly increased following insulin administration. Similarly, addition of insulin in vitro did not change the transport activity significantly. When rats are made diabetic on administration of alloxan monohydrate, the transport activity is increased. Hydrocortisone, adrenocorticotrophic hormone and thyroxine treatment increased the absorption of L-histidine by small intestine. However, addition in vitro of ACTH and hydrocortisone did not change the absorption of L-histidines by small intestine. It appears that the facilitative action of these hormones is not due to their direct action of the membrane."} {"id": "PMID:169206", "title": "Adenosine 3',5'-monophosphate analogue increases the outflow facility of the primate eye.", "content": "Our previous studies showed that cyclic-AMP increases the outflow facility of the eye of the rabbit. In this investigation, an analogue of cyclic-AMP, the 8-methylthio derivative, perfused into the anterior chamber of the eye of the vervet monkey, increased outflow facility twofold. This observation supports the hypothesis that cyclic-AMP mediates the action of adrenergic agents to reduce intraocular pressure in the primate eye.", "contents": "Adenosine 3',5'-monophosphate analogue increases the outflow facility of the primate eye. Our previous studies showed that cyclic-AMP increases the outflow facility of the eye of the rabbit. In this investigation, an analogue of cyclic-AMP, the 8-methylthio derivative, perfused into the anterior chamber of the eye of the vervet monkey, increased outflow facility twofold. This observation supports the hypothesis that cyclic-AMP mediates the action of adrenergic agents to reduce intraocular pressure in the primate eye."} {"id": "PMID:169208", "title": "Tracheobronchial resection and reconstruction. A report of five cases.", "content": "During the past six years, five patients have undergone tracheal or tracheobronchial reconstruction in our Department. In three patients, a segmental tracheal resection was performed because of post-tracheostomy stricture or cylindroma of the trachea. Two patients were treated for a carcinoid type of bronchial adenoma--one by sleeve resection of an intermediate bronchus and one by pneumonectomy with partial resection and reconstruction of part of the trachea. The exact location, length and nature of the lesions were demonstrated by endoscopy, tomography and tracheobronchography. The surgical and anesthetic problems associated with tracheobronchial reconstruction are discussed.", "contents": "Tracheobronchial resection and reconstruction. A report of five cases. During the past six years, five patients have undergone tracheal or tracheobronchial reconstruction in our Department. In three patients, a segmental tracheal resection was performed because of post-tracheostomy stricture or cylindroma of the trachea. Two patients were treated for a carcinoid type of bronchial adenoma--one by sleeve resection of an intermediate bronchus and one by pneumonectomy with partial resection and reconstruction of part of the trachea. The exact location, length and nature of the lesions were demonstrated by endoscopy, tomography and tracheobronchography. The surgical and anesthetic problems associated with tracheobronchial reconstruction are discussed."} {"id": "PMID:169220", "title": "Estrogen treatment of excessively tall girls.", "content": "40 excessively tall girls with a mean height prediction of 182 cm were treated for serious psychosocial reasons continuously with ethinylestradiol 0.3 mg daily and with norethisterone 10 mg daily for 5-7 days every 4th week. Their age at the start of treatment ranged from 9.4 to 13.8 years, and the mean duration of treatment was 1.7 years. Bone age was assessed according to the TANNER-WHITEHOUSE-II (RUS) method, and height predictions were calculated using the age-specific regression equations of TANNER et al. Results were compared with those in 9 untreated control cases. Mean reduction of predicted height in all patients was 4.6 +/- 2.4 cm, and the most marked reduction was found in the youngest group of patients. However, even in patients after menarche and with a bone age above 14 years at start of treatment, there was still a considerable reduction of adult height. Bone maturation was accelerated by treatment (1.4 years per year), and the most marked acceleration was observed during the first 6 months (1.7 years per year). Growth velocity was normal or slightly subnormal during the first 6 months and very low thereafter. During treatment, there was a considerable weight gain which was, in part, lost again when treatment was discontinued. Posttherapeutic amenorrhea was infrequent, and normal and regular menstruations reappeared in the majority of the patients about 1 month after discontinuation. It is concluded that estrogen treatment in high doses is effective in reducing adult stature in girls and that somatic and psychological side effects are minimal when treatment is started after onset of spontaneous puberty. Although early treatment tends to give better results, beneficial results may still be obtained in older patients.", "contents": "Estrogen treatment of excessively tall girls. 40 excessively tall girls with a mean height prediction of 182 cm were treated for serious psychosocial reasons continuously with ethinylestradiol 0.3 mg daily and with norethisterone 10 mg daily for 5-7 days every 4th week. Their age at the start of treatment ranged from 9.4 to 13.8 years, and the mean duration of treatment was 1.7 years. Bone age was assessed according to the TANNER-WHITEHOUSE-II (RUS) method, and height predictions were calculated using the age-specific regression equations of TANNER et al. Results were compared with those in 9 untreated control cases. Mean reduction of predicted height in all patients was 4.6 +/- 2.4 cm, and the most marked reduction was found in the youngest group of patients. However, even in patients after menarche and with a bone age above 14 years at start of treatment, there was still a considerable reduction of adult height. Bone maturation was accelerated by treatment (1.4 years per year), and the most marked acceleration was observed during the first 6 months (1.7 years per year). Growth velocity was normal or slightly subnormal during the first 6 months and very low thereafter. During treatment, there was a considerable weight gain which was, in part, lost again when treatment was discontinued. Posttherapeutic amenorrhea was infrequent, and normal and regular menstruations reappeared in the majority of the patients about 1 month after discontinuation. It is concluded that estrogen treatment in high doses is effective in reducing adult stature in girls and that somatic and psychological side effects are minimal when treatment is started after onset of spontaneous puberty. Although early treatment tends to give better results, beneficial results may still be obtained in older patients."} {"id": "PMID:169224", "title": "Isolation and characterization of Clostridium perfringens mutants altered in both hemagglutinin and sialidase production.", "content": "The relationship between the production of hemagglutinin and sialidase activities by Clostridium perfringens was investigated by screening for mutants producing reduced levels of hemagglutinin activity. Twelve mutants were isolated; all produced reduced levels of sialidase activity and several had other altered phenotypic markers. Revertants that regained the ability to produce active hemagglutinin were isolated. All of these revertants produced increased sialidase activity. These results show that the production of hemagglutinin activity is directly related to the production of sialidase activity. Evidence is also presented that the processes of sporulation and the production of extracellular proteins are interrelated.", "contents": "Isolation and characterization of Clostridium perfringens mutants altered in both hemagglutinin and sialidase production. The relationship between the production of hemagglutinin and sialidase activities by Clostridium perfringens was investigated by screening for mutants producing reduced levels of hemagglutinin activity. Twelve mutants were isolated; all produced reduced levels of sialidase activity and several had other altered phenotypic markers. Revertants that regained the ability to produce active hemagglutinin were isolated. All of these revertants produced increased sialidase activity. These results show that the production of hemagglutinin activity is directly related to the production of sialidase activity. Evidence is also presented that the processes of sporulation and the production of extracellular proteins are interrelated."} {"id": "PMID:169225", "title": "Pyrimidine biosynthetic pathway of Baccillus subtilis.", "content": "Biochemical and genetic data were obtained from a series of 51 Pyr- strains of Bacillus subtilis. The observed enzymatic deficiencies allowed the mutants to be placed into 12 clases, some of which represent defects in more than one of the six known pyrimidine biosynthetic enzymes. Mapping analysis by transformation has shown that all the Pyr- mutations are located in a single small area of the B. subtilis genome. A correlation of the biochemical defects and the genetic data has been made. Those mutations conferring similar enzymatic deficiencies were found to be contiguous on the B. subtilis map. Regulatory aspects of the pyrimidine pathway have also been investigated and are compared to previously reported results from other organisms. Evidence is presented which bears upon the possible physical association of the first three enzymes and the association of at least some of the enzymes of this pathway with particulate elements of the cell. A model for the organization of the enzymes is presented with dihydroorotate dehydrogenase as the central enzyme in a proposed aggregate.", "contents": "Pyrimidine biosynthetic pathway of Baccillus subtilis. Biochemical and genetic data were obtained from a series of 51 Pyr- strains of Bacillus subtilis. The observed enzymatic deficiencies allowed the mutants to be placed into 12 clases, some of which represent defects in more than one of the six known pyrimidine biosynthetic enzymes. Mapping analysis by transformation has shown that all the Pyr- mutations are located in a single small area of the B. subtilis genome. A correlation of the biochemical defects and the genetic data has been made. Those mutations conferring similar enzymatic deficiencies were found to be contiguous on the B. subtilis map. Regulatory aspects of the pyrimidine pathway have also been investigated and are compared to previously reported results from other organisms. Evidence is presented which bears upon the possible physical association of the first three enzymes and the association of at least some of the enzymes of this pathway with particulate elements of the cell. A model for the organization of the enzymes is presented with dihydroorotate dehydrogenase as the central enzyme in a proposed aggregate."} {"id": "PMID:169226", "title": "Effects of varying the carbon source limiting growth on yield and maintenance characteristics of Escherichia coli in continuous culture.", "content": "The magnitudes of Yo (grams [dry weight] formed per gram of atom O) and mo, the maintenance respiration (milligram-atoms of O per gram [dry weight] per hour), of Escherichia coli B have been determined by growing the organism in aerobic continuous culture limited by a number of different substrates. The value found were as follows: glucose--tyo = 12.5, mo = 0.9; glucose plus 2.7 mM cyclic adenosine 3',5'-monophosphate (cAMP)--Yo = 31.2, mo = 9.3; galactose--Yo = 13.2, mo = 1.8; mannitol--Yo = 20.1, mo = 6.1; L-glutamate--Yo = 25.5, mo = 17.7; glycerol--Yo = 14.9, mo = 10.0; succinate--Yo = 11.2, mo = 12.1; and acetate--Yo = 14.7, mo = 25.4. During growth in anaerobic continuous culture with limiting glucose YATP was found to be 10.3 g (dry weight)/mol of adenosine 5'-triphosphate (ATP) and m ATP was 18.9 mmol of ATP/g (dry weight) per h. The aerobic growth yields of cells growing on glucose, glucose plus cAMP, mannitol, and glutamate were consistent with the hypothesis that carbohydrates partially repress oxidative phosphorylation, but the yields of cells growing on glycerol, succinate, acetate, and galactose were all lower than expected. We conclude that, like the efficiency of oxidative phosphorylation, both the maintenance respiration and the amount of ATP necessary to serve maintenance processes are determined by the identity of the growth substrates. Yields smaller than expected may be explained by the absence of respiratory control exerted by phosphate acceptors.", "contents": "Effects of varying the carbon source limiting growth on yield and maintenance characteristics of Escherichia coli in continuous culture. The magnitudes of Yo (grams [dry weight] formed per gram of atom O) and mo, the maintenance respiration (milligram-atoms of O per gram [dry weight] per hour), of Escherichia coli B have been determined by growing the organism in aerobic continuous culture limited by a number of different substrates. The value found were as follows: glucose--tyo = 12.5, mo = 0.9; glucose plus 2.7 mM cyclic adenosine 3',5'-monophosphate (cAMP)--Yo = 31.2, mo = 9.3; galactose--Yo = 13.2, mo = 1.8; mannitol--Yo = 20.1, mo = 6.1; L-glutamate--Yo = 25.5, mo = 17.7; glycerol--Yo = 14.9, mo = 10.0; succinate--Yo = 11.2, mo = 12.1; and acetate--Yo = 14.7, mo = 25.4. During growth in anaerobic continuous culture with limiting glucose YATP was found to be 10.3 g (dry weight)/mol of adenosine 5'-triphosphate (ATP) and m ATP was 18.9 mmol of ATP/g (dry weight) per h. The aerobic growth yields of cells growing on glucose, glucose plus cAMP, mannitol, and glutamate were consistent with the hypothesis that carbohydrates partially repress oxidative phosphorylation, but the yields of cells growing on glycerol, succinate, acetate, and galactose were all lower than expected. We conclude that, like the efficiency of oxidative phosphorylation, both the maintenance respiration and the amount of ATP necessary to serve maintenance processes are determined by the identity of the growth substrates. Yields smaller than expected may be explained by the absence of respiratory control exerted by phosphate acceptors."} {"id": "PMID:169227", "title": "Two modes of excision repair in toluene-treated Escherichia coli.", "content": "In toluene-treated Escherichia coli incision breaks accumulate during post-irradiation incubation in the presence of adenosine 5'-triphosphate (ATP). It is shown that incised deoxyribonucleic acid (DNA) is converted to high-molecular-weight DNA during reincubation in the presence of the four deoxyribonucleoside triphosphates (dNTP's) and nicotinamide adenine dinucleotide (NAD). This restitution process is ATP independent and N-ethylmaleimide insensitive and takes place only in polA+ strains. It is defective in strains carrying a mutation in the 5' leads to 3' exonucleolytic activity associated with DNA polymerase I. Repair of accumulated incision breaks differs from repair in which all the steps of the excision repair process occur simultaneously or in rapid succession. The latter is observed if toluene-treated E. coli are incubated immediately after irradiation in the presence of the four dNTP's, NAD, and ATP. It is shown that under these conditions dimer excision occurs to a larger extent than during repair of accumulated incision breaks and that, except in strains defective in polynucleotide ligase, incision breaks do not accumulate. This consecutive mode of repair is detectable in polA+ strains and at low doses also in polA mutants.", "contents": "Two modes of excision repair in toluene-treated Escherichia coli. In toluene-treated Escherichia coli incision breaks accumulate during post-irradiation incubation in the presence of adenosine 5'-triphosphate (ATP). It is shown that incised deoxyribonucleic acid (DNA) is converted to high-molecular-weight DNA during reincubation in the presence of the four deoxyribonucleoside triphosphates (dNTP's) and nicotinamide adenine dinucleotide (NAD). This restitution process is ATP independent and N-ethylmaleimide insensitive and takes place only in polA+ strains. It is defective in strains carrying a mutation in the 5' leads to 3' exonucleolytic activity associated with DNA polymerase I. Repair of accumulated incision breaks differs from repair in which all the steps of the excision repair process occur simultaneously or in rapid succession. The latter is observed if toluene-treated E. coli are incubated immediately after irradiation in the presence of the four dNTP's, NAD, and ATP. It is shown that under these conditions dimer excision occurs to a larger extent than during repair of accumulated incision breaks and that, except in strains defective in polynucleotide ligase, incision breaks do not accumulate. This consecutive mode of repair is detectable in polA+ strains and at low doses also in polA mutants."} {"id": "PMID:169228", "title": "Transient repression of catabolite-sensitive enzyme synthesis elicited by 2,4-dinitrophenol.", "content": "Transient inhibition of catabolic enzyme synthesis in Escherichia coli occurred when a low concentration of 2,4-dinitrophenol (DNP) was simultaneously added with inducer. Using mutant strains defective for gamma-gene product or constitutive for lac enzymes, it was found that the inhibition is not due to the exclusion of inducer by uncoupling. The addition of cyclic adenosine 3',5'-monophosphate overcame repression. The components of the lac operon coordinately responded to DNP inhibition. From deoxyribonucleic acid-ribonucleic acid hybridization experiments, it was found that the inhibition of beta-galactosidase induction occurred at the level of messenger ribonucleic acid synthesis specific for the lac operon. It seems probable that DNP represses induction in a similar manner to that of transient repression observed upon the addition of glucose. Furthermore, it was found that transient repression disappeared if cells were preincubated with DNP before induction. This indicates that new contact of cells with DNP is obligatory for transient repression. From these results, it is suggested that the cell membrane may be responsible for regulation of catabolite-sensitive enzyme synthesis.", "contents": "Transient repression of catabolite-sensitive enzyme synthesis elicited by 2,4-dinitrophenol. Transient inhibition of catabolic enzyme synthesis in Escherichia coli occurred when a low concentration of 2,4-dinitrophenol (DNP) was simultaneously added with inducer. Using mutant strains defective for gamma-gene product or constitutive for lac enzymes, it was found that the inhibition is not due to the exclusion of inducer by uncoupling. The addition of cyclic adenosine 3',5'-monophosphate overcame repression. The components of the lac operon coordinately responded to DNP inhibition. From deoxyribonucleic acid-ribonucleic acid hybridization experiments, it was found that the inhibition of beta-galactosidase induction occurred at the level of messenger ribonucleic acid synthesis specific for the lac operon. It seems probable that DNP represses induction in a similar manner to that of transient repression observed upon the addition of glucose. Furthermore, it was found that transient repression disappeared if cells were preincubated with DNP before induction. This indicates that new contact of cells with DNP is obligatory for transient repression. From these results, it is suggested that the cell membrane may be responsible for regulation of catabolite-sensitive enzyme synthesis."} {"id": "PMID:169229", "title": "pyrR identical to pyrH in Salmonella typhimurium: control of expression of the pyr genes.", "content": "Mutants of Salmonella typhimurium showing constitutive synthesis of the pyrimidine biosynthetic enzymes coded for by the pyrA-F genes (G. A. O'Donavan and J. C. Gerhart, 1972) have been reinvestigated. The high rate of expression of the pyrB-F genes in these mutants as well as their pyrimidine excretion is shown to be due to mutations in the gene pyrH encoding uridine 5'-monophosphate kinase. Thus, the term pyrR used for these mutants should be replaced by the designation pyrH.", "contents": "pyrR identical to pyrH in Salmonella typhimurium: control of expression of the pyr genes. Mutants of Salmonella typhimurium showing constitutive synthesis of the pyrimidine biosynthetic enzymes coded for by the pyrA-F genes (G. A. O'Donavan and J. C. Gerhart, 1972) have been reinvestigated. The high rate of expression of the pyrB-F genes in these mutants as well as their pyrimidine excretion is shown to be due to mutations in the gene pyrH encoding uridine 5'-monophosphate kinase. Thus, the term pyrR used for these mutants should be replaced by the designation pyrH."} {"id": "PMID:169230", "title": "Tryptophan biosynthesis in Salmonella typhimurium: location in trpB of a genetic difference between strains LT2 and LT7.", "content": "Salmonella typhimurium prototrophs carrying a trpR mutation synthesize tryptophan biosynthetic enzymes constitutively. When feedback inhibition of anthranilate synthetase but not 5'-phosphoribosylpyrophosphate phosphoribosyltransferase activity was by-passed by growing cells on media supplemented with anthranilic acid, all trpR prototrophs overproduced and excreted tryptophan. However, the rate of tryptophan production depended on both the ancestry of the trpR strain and the integrity of its trpA gene. Prototrophs with trp genes derived from S. typhimurium strain LT2 produced tryptophan more efficiently than those with trp genes derived from strain LT7. This strain difference was cryptic insofar as it did not affect the growth rate; it was revealed only as a rate-limiting step in the constitutive biosynthesis of tryptophan in the presence of anthranilic acid, and was due to a lesion in the LT7-derived trpB gene. Strains with LT7-derived trp genes bearing a deletion in trpA produced tryptophan as readily as LT2 trpR prototrophs. This indicated that LT7-specific 5-phosphoribosylpyrophosphate phosphoribosyltransferase must be aggregated with the trpA gene produce to give an observable reduction of constitutive tryptophan production. The discovery of this strain difference has particular implications for studies involving the activities of trpA and B genes and their products in S. typhimurium and may have general significance for other studies involving different strains of Salmonella.", "contents": "Tryptophan biosynthesis in Salmonella typhimurium: location in trpB of a genetic difference between strains LT2 and LT7. Salmonella typhimurium prototrophs carrying a trpR mutation synthesize tryptophan biosynthetic enzymes constitutively. When feedback inhibition of anthranilate synthetase but not 5'-phosphoribosylpyrophosphate phosphoribosyltransferase activity was by-passed by growing cells on media supplemented with anthranilic acid, all trpR prototrophs overproduced and excreted tryptophan. However, the rate of tryptophan production depended on both the ancestry of the trpR strain and the integrity of its trpA gene. Prototrophs with trp genes derived from S. typhimurium strain LT2 produced tryptophan more efficiently than those with trp genes derived from strain LT7. This strain difference was cryptic insofar as it did not affect the growth rate; it was revealed only as a rate-limiting step in the constitutive biosynthesis of tryptophan in the presence of anthranilic acid, and was due to a lesion in the LT7-derived trpB gene. Strains with LT7-derived trp genes bearing a deletion in trpA produced tryptophan as readily as LT2 trpR prototrophs. This indicated that LT7-specific 5-phosphoribosylpyrophosphate phosphoribosyltransferase must be aggregated with the trpA gene produce to give an observable reduction of constitutive tryptophan production. The discovery of this strain difference has particular implications for studies involving the activities of trpA and B genes and their products in S. typhimurium and may have general significance for other studies involving different strains of Salmonella."} {"id": "PMID:169231", "title": "Kinetics of the onset of catabolite repression in Escherichia coli as determined by lac messenger ribonucleic acid initiations and intracellular cyclic adenosine 3',5'-monophosphate levels.", "content": "The rates of synthesis of beta-galactosidase (EC 3.2.1.23) and the intracellular levels of cyclic 3',5'-adenosine monophosphate (cAMP) soon after the addition of glucose or glycerol to exponentially growing cultures of Escherichia coli have been determined. Within 10 s of its addition, glucose, but not glycerol, lowered the apparent initiation frequency of lac messenger ribonucleic acid. The glucose-generated reduction in initiations is identified as catabolite repression by its reversibility with cAMP. The intracellular cAMP levels respond virtually identically to glucose and glycerol additions. Thus, no correlation was observed between the rate of messenger ribonucleic acid initiation and the level of cAMP.", "contents": "Kinetics of the onset of catabolite repression in Escherichia coli as determined by lac messenger ribonucleic acid initiations and intracellular cyclic adenosine 3',5'-monophosphate levels. The rates of synthesis of beta-galactosidase (EC 3.2.1.23) and the intracellular levels of cyclic 3',5'-adenosine monophosphate (cAMP) soon after the addition of glucose or glycerol to exponentially growing cultures of Escherichia coli have been determined. Within 10 s of its addition, glucose, but not glycerol, lowered the apparent initiation frequency of lac messenger ribonucleic acid. The glucose-generated reduction in initiations is identified as catabolite repression by its reversibility with cAMP. The intracellular cAMP levels respond virtually identically to glucose and glycerol additions. Thus, no correlation was observed between the rate of messenger ribonucleic acid initiation and the level of cAMP."} {"id": "PMID:169232", "title": "A kinetic study of the alpha-keto acid dehydrogenase complexes from pig heart mitochondria.", "content": "The kinetic mechanisms of the 2-oxoglutarate and pyruvate dehydrogenease complexes from pig heart mitochondria were studied at pH 7.5 and 25 degrees. A three-site ping-pong mechanism for the actin of both complexes was proposed on the basis of the parallel lines obtained when 1/v was plotted against 2-oxoglutarate or pyruvate concentration for various levels of CoA and a level of NAD+ near its Michaelis constant value. Rate equations were derived from the proposed mechanism. Michaelis constants for the reactants of the 2-oxoglutarate dehydrogenase complex reaction are: 2-oxoglutarate, 0.220 mM; CoA, 0.025 mM; NAD+, 0.050 mM. Those of the pyruvate dehydrogenase complex are: pyruvate, 0.015 mM; CoA, 0.021 mM; NAD+, 0.079 mM. Product inhibition studies showed that succinyl-CoA or acetyl-CoA was competitive with respect to CoA, and NADH was competitive with respect to NAD+ in both overall reactions, and that succinyl-CoA or acetyl-CoA and NADH were uncompetitive with respect to 2-oxoglutarate or pyruvate, respectively. However, noncompetitive (rather than uncompetitive) inhibition patterns were observed for succinyl-CoA or acetyl-CoA versus NAD+ and for NADH versus CoA. These results are consistent with the proposed mechanisms.", "contents": "A kinetic study of the alpha-keto acid dehydrogenase complexes from pig heart mitochondria. The kinetic mechanisms of the 2-oxoglutarate and pyruvate dehydrogenease complexes from pig heart mitochondria were studied at pH 7.5 and 25 degrees. A three-site ping-pong mechanism for the actin of both complexes was proposed on the basis of the parallel lines obtained when 1/v was plotted against 2-oxoglutarate or pyruvate concentration for various levels of CoA and a level of NAD+ near its Michaelis constant value. Rate equations were derived from the proposed mechanism. Michaelis constants for the reactants of the 2-oxoglutarate dehydrogenase complex reaction are: 2-oxoglutarate, 0.220 mM; CoA, 0.025 mM; NAD+, 0.050 mM. Those of the pyruvate dehydrogenase complex are: pyruvate, 0.015 mM; CoA, 0.021 mM; NAD+, 0.079 mM. Product inhibition studies showed that succinyl-CoA or acetyl-CoA was competitive with respect to CoA, and NADH was competitive with respect to NAD+ in both overall reactions, and that succinyl-CoA or acetyl-CoA and NADH were uncompetitive with respect to 2-oxoglutarate or pyruvate, respectively. However, noncompetitive (rather than uncompetitive) inhibition patterns were observed for succinyl-CoA or acetyl-CoA versus NAD+ and for NADH versus CoA. These results are consistent with the proposed mechanisms."} {"id": "PMID:169233", "title": "Photoreduction of cytochrome c1.", "content": "1. Ferricytochrome c1 solution was reduced completely between pH 7 and 10 by illumination under anaerobic conditions. Photoreduction was not affected by the ionic strength of the medium. However, it did not take place at pH lower than 6 or higher than 10, or in the presence of p-hydroxymercuric benzoate. The ferricyanide-reoxidized photoreduced c1 was not further reduced upon illumination. The reductant was most probably a specific sulfhydryl group in the subunit containing the heme of the cytochrome since this subunit contained one less p-HMB-titratable group in the photoreduced sample than in the untreated preparation. 2. The photoreduced cytochrome c1 showed the same spectra as the native cytochrome, and was not reactive with carbon monoxide. The equilibrium constant of the reaction c12+ + c3+ equilibrium c13+ + c2+ for the photoreduced c1 was found to be slightly lower (Keq = 2.6) than that for the native c1 (Keq = 3.5). The antimycin A-sensitive electron acceptor activity of ferricyanide-reoxidized photoreduced c13+ catalyzed by succinate-cytochrome c reductase was about 80% of that of the native c1. 3. A somewhat simplified method for isolation of cytochrome c1 was developed. Anaerobic ammonium sulfate fractionation and calcium phosphate gel chromatography were still used in order to achieve the purity level of about 25 nmol of heme/mg of protein. The cytochrome c1 prepared by this procedure showed the same properties tested as that by the beta-mercaptoethanol method (Yu, C.A., Yu, L., and King, T.E. (1972) J. Biol. Chem. 247, 1012-1019).", "contents": "Photoreduction of cytochrome c1. 1. Ferricytochrome c1 solution was reduced completely between pH 7 and 10 by illumination under anaerobic conditions. Photoreduction was not affected by the ionic strength of the medium. However, it did not take place at pH lower than 6 or higher than 10, or in the presence of p-hydroxymercuric benzoate. The ferricyanide-reoxidized photoreduced c1 was not further reduced upon illumination. The reductant was most probably a specific sulfhydryl group in the subunit containing the heme of the cytochrome since this subunit contained one less p-HMB-titratable group in the photoreduced sample than in the untreated preparation. 2. The photoreduced cytochrome c1 showed the same spectra as the native cytochrome, and was not reactive with carbon monoxide. The equilibrium constant of the reaction c12+ + c3+ equilibrium c13+ + c2+ for the photoreduced c1 was found to be slightly lower (Keq = 2.6) than that for the native c1 (Keq = 3.5). The antimycin A-sensitive electron acceptor activity of ferricyanide-reoxidized photoreduced c13+ catalyzed by succinate-cytochrome c reductase was about 80% of that of the native c1. 3. A somewhat simplified method for isolation of cytochrome c1 was developed. Anaerobic ammonium sulfate fractionation and calcium phosphate gel chromatography were still used in order to achieve the purity level of about 25 nmol of heme/mg of protein. The cytochrome c1 prepared by this procedure showed the same properties tested as that by the beta-mercaptoethanol method (Yu, C.A., Yu, L., and King, T.E. (1972) J. Biol. Chem. 247, 1012-1019)."} {"id": "PMID:169234", "title": "Amino acid sequence homology of mammalian type C RNA virus major internal proteins.", "content": "The NH2-terminal amino acid sequence of the major group-specific antigen, the major internal virion protein (p30; approximate molecular weight 30,000) of several mammalian type C RNA viruses was determined by the Edman degradation procedure using an automated protein sequenator. All of the proteins analyzed show a high degree of over-all sequence homology and also contain specific regions or single residues. All p30s begin with the sequence prolyl-leucylarginyl (Pro-Leu-Arg) and have an invariant, conserved region from residues 11 to 24. In this region only a single amino acid difference appears between the cat and mouse p30s. At position 17 alanine is found in the cat, and serine in all the mouse proteins. This homologous region starts at position 10 for RD-114 and baboon virus p30s, and at position 18 in the protein of the virus isolated from gibbon ape. The region extending from residue 4 to 10 shows considerable variability between p30s isolated from different mammalian species. Out of 24 residues compared, only a single amino acid difference was found between six different mouse p30s. At position 4, three have leucine, two have alanine, and one has serine. The comparative sequence data demonstrate that the viral p30s are products of related genes in the viruses from various mammalian species.", "contents": "Amino acid sequence homology of mammalian type C RNA virus major internal proteins. The NH2-terminal amino acid sequence of the major group-specific antigen, the major internal virion protein (p30; approximate molecular weight 30,000) of several mammalian type C RNA viruses was determined by the Edman degradation procedure using an automated protein sequenator. All of the proteins analyzed show a high degree of over-all sequence homology and also contain specific regions or single residues. All p30s begin with the sequence prolyl-leucylarginyl (Pro-Leu-Arg) and have an invariant, conserved region from residues 11 to 24. In this region only a single amino acid difference appears between the cat and mouse p30s. At position 17 alanine is found in the cat, and serine in all the mouse proteins. This homologous region starts at position 10 for RD-114 and baboon virus p30s, and at position 18 in the protein of the virus isolated from gibbon ape. The region extending from residue 4 to 10 shows considerable variability between p30s isolated from different mammalian species. Out of 24 residues compared, only a single amino acid difference was found between six different mouse p30s. At position 4, three have leucine, two have alanine, and one has serine. The comparative sequence data demonstrate that the viral p30s are products of related genes in the viruses from various mammalian species."} {"id": "PMID:169235", "title": "The purine nucleotide cycle. Control of phosphofructokinase and glycolytic oscillations in muscle extracts.", "content": "Linked oscillations of the glycolytic pathway and the purine nucleotide cycle were studied in particle-free extracts of rat skeletal muscle. Under the conditions used, an accumulation of about 1 muM fructose diphosphate can trigger a sudden increase in phosphofructokinase activity. The activation by fructose diphosphate depends on the presence of AMP. When the AMP concentration drops, phosphofructokinase becomes inhibited, even though the fructose disphosphate concentration remains high. It is concluded that the oscillatory behavior can be of advantage for maintaining a high average [ATP]/[ADP] ratio.", "contents": "The purine nucleotide cycle. Control of phosphofructokinase and glycolytic oscillations in muscle extracts. Linked oscillations of the glycolytic pathway and the purine nucleotide cycle were studied in particle-free extracts of rat skeletal muscle. Under the conditions used, an accumulation of about 1 muM fructose diphosphate can trigger a sudden increase in phosphofructokinase activity. The activation by fructose diphosphate depends on the presence of AMP. When the AMP concentration drops, phosphofructokinase becomes inhibited, even though the fructose disphosphate concentration remains high. It is concluded that the oscillatory behavior can be of advantage for maintaining a high average [ATP]/[ADP] ratio."} {"id": "PMID:169236", "title": "Purification and properties of the light-activated cyclic nucleotide phosphodiesterase of rod outer segments.", "content": "Frog (Rana catesbiana) rod outer segment disc membranes contain a cyclic nucleotide phosphodiesterase (EC 3.1.4.17) which is activated by light in the presence of ATP. This enzyme is firmly bound to the disc membrane, but can be eluted from the membrane with 10 mM Tris-HCl buffer, pH 7.4 and 2 mM EDTA. The eluted phosphodiesterase has reduced activity, but can be activated approximately 10-fold by polycations such as protamine and polylysine. The eluted phosphodiesterase can no longer be activated by light in the presence of ATP, that is, activation by light apparently depends on the native orientation of phosphodiesterase in relationship to other disc membrane components. The eluted phosphodiesterase was purified to homogeneity as judged by analytical polyacrylamide gel electrophoresis and polyacrylamide gel isoelectric focusing. The over-all purification from intact retina was approximately 925-fold. The purification of phosphodiesterase from the isolated rod outer segment preparation was about 185-fold with a 28% yield. Phosphodiesterase accounts for approximately 0.5% of the disc membrane protein. The eluted phosphodiesterase (inactive form) has a sedimentation coefficient of 12.4 S corresponding to an approximate molecular weight of 240,000. Sodium dodecyl sulfate polyacrylamide gel electrophoresis separates the purified phosphodiesterase into two subunits of 120,000 and 110,000 daltons. With cyclic 3':5'-GMP (cGMP) as substrate the Km for the purified phosphodiesterase is 70 muM. Protamine increases the Vmax without changing the Km for cGMP. The isoelectric point (pI) of the native dimer is 5.7. Limited exposure of the eluted phosphodiesterase (inactive form) to trypsin produces a somewhat greater activation than is obtained with 0.5 mg/ml of protamine. The trypsin-activated phosphodiesterase has a sedimentation coefficient of 7.8 S corresponding to an approximate molecular weight of 170,000. The 110,000-dalton subunit is much less sensitive to trypsin hydrolysis and the 120,000-dalton subunit is rapidly replaced by smaller fragments. On the basis of the molecular weight of the purified phosphodiesterase (240,000) and the concentrations of phosphodiesterase and rhodopsin in the rod outer segment, it is estimated that the molar ratio ophosphodiesterase to rhodopsin in the rod outer segment is approximately 1:900. Since all of the disc phosphodiesterase molecules are activated when 0.1% of the rhodopsins are bleached, we conclude that in the presence of ATP 1 molecule of bleached rhodopsin can activate 1 molecule of phosphodiesterase.", "contents": "Purification and properties of the light-activated cyclic nucleotide phosphodiesterase of rod outer segments. Frog (Rana catesbiana) rod outer segment disc membranes contain a cyclic nucleotide phosphodiesterase (EC 3.1.4.17) which is activated by light in the presence of ATP. This enzyme is firmly bound to the disc membrane, but can be eluted from the membrane with 10 mM Tris-HCl buffer, pH 7.4 and 2 mM EDTA. The eluted phosphodiesterase has reduced activity, but can be activated approximately 10-fold by polycations such as protamine and polylysine. The eluted phosphodiesterase can no longer be activated by light in the presence of ATP, that is, activation by light apparently depends on the native orientation of phosphodiesterase in relationship to other disc membrane components. The eluted phosphodiesterase was purified to homogeneity as judged by analytical polyacrylamide gel electrophoresis and polyacrylamide gel isoelectric focusing. The over-all purification from intact retina was approximately 925-fold. The purification of phosphodiesterase from the isolated rod outer segment preparation was about 185-fold with a 28% yield. Phosphodiesterase accounts for approximately 0.5% of the disc membrane protein. The eluted phosphodiesterase (inactive form) has a sedimentation coefficient of 12.4 S corresponding to an approximate molecular weight of 240,000. Sodium dodecyl sulfate polyacrylamide gel electrophoresis separates the purified phosphodiesterase into two subunits of 120,000 and 110,000 daltons. With cyclic 3':5'-GMP (cGMP) as substrate the Km for the purified phosphodiesterase is 70 muM. Protamine increases the Vmax without changing the Km for cGMP. The isoelectric point (pI) of the native dimer is 5.7. Limited exposure of the eluted phosphodiesterase (inactive form) to trypsin produces a somewhat greater activation than is obtained with 0.5 mg/ml of protamine. The trypsin-activated phosphodiesterase has a sedimentation coefficient of 7.8 S corresponding to an approximate molecular weight of 170,000. The 110,000-dalton subunit is much less sensitive to trypsin hydrolysis and the 120,000-dalton subunit is rapidly replaced by smaller fragments. On the basis of the molecular weight of the purified phosphodiesterase (240,000) and the concentrations of phosphodiesterase and rhodopsin in the rod outer segment, it is estimated that the molar ratio ophosphodiesterase to rhodopsin in the rod outer segment is approximately 1:900. Since all of the disc phosphodiesterase molecules are activated when 0.1% of the rhodopsins are bleached, we conclude that in the presence of ATP 1 molecule of bleached rhodopsin can activate 1 molecule of phosphodiesterase."} {"id": "PMID:169237", "title": "Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats.", "content": "Glucagon can stimulate gluconeogenesis from 2 mM lactate nearly 4-fold in isolated liver cells from fed rats; exogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP) is equally effective, but epinephrine can stimulate only 1.5-fold. Half-maximal effects are obtained with glucagon at 0.3 nM, cyclic AMP at 30 muM and epinephrine at 0.2 muM. Insulin reduces by 50% the stimulation by suboptimal concentrations of glucagon (0.5 nM). A half-maximal effect is obtained with 0.3 nM insulin (45 microunits/ml). Glucagon in the presence of theophylline (1 mM) causes a rapid rise and subsequent fall in intracellular cyclic AMP with a peak between 3 and 6 min. Some of the fall can be accounted for by loss of nucleotide into the medium. This efflux is suppressed by probenecid, suggesting the presence of a membrane transport mechanism for the cyclic nucleotide. Glucagon can raise intracellular cyclic AMP about 30-fold; a half-maximal effect is obtained with 1.5 nM hormone. Epinephrine (plus theophylline, 1 mM) can raise intracellular cyclic AMP about 2-fold; the peak elevation is reached in less than 1 min and declines during the next 15 min to near the basal level. Insulin (10 nM) does not lower the basal level of cyclic AMP within the hepatocyte, but suppresses by about 50% the rise in intracellular and total cyclic AMP caused by exposure to an intermediate concentration of glucagon. No inhibition of adenylate cyclase by insulin can be shown. Basal gluconeogenesis is not significantly depressed by calcium deficiency but stimulation by glucagon is reduced by 50%. Calcium deficiency does not reduce accumulation of cyclic AMP in response to glucagon but diminishes stimulation of gluconeogenesis by exogenous cyclic AMP. Glucagon has a rapid stimulatory effect on the flux of 45Ca2+ from medium to tissue.", "contents": "Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats. Glucagon can stimulate gluconeogenesis from 2 mM lactate nearly 4-fold in isolated liver cells from fed rats; exogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP) is equally effective, but epinephrine can stimulate only 1.5-fold. Half-maximal effects are obtained with glucagon at 0.3 nM, cyclic AMP at 30 muM and epinephrine at 0.2 muM. Insulin reduces by 50% the stimulation by suboptimal concentrations of glucagon (0.5 nM). A half-maximal effect is obtained with 0.3 nM insulin (45 microunits/ml). Glucagon in the presence of theophylline (1 mM) causes a rapid rise and subsequent fall in intracellular cyclic AMP with a peak between 3 and 6 min. Some of the fall can be accounted for by loss of nucleotide into the medium. This efflux is suppressed by probenecid, suggesting the presence of a membrane transport mechanism for the cyclic nucleotide. Glucagon can raise intracellular cyclic AMP about 30-fold; a half-maximal effect is obtained with 1.5 nM hormone. Epinephrine (plus theophylline, 1 mM) can raise intracellular cyclic AMP about 2-fold; the peak elevation is reached in less than 1 min and declines during the next 15 min to near the basal level. Insulin (10 nM) does not lower the basal level of cyclic AMP within the hepatocyte, but suppresses by about 50% the rise in intracellular and total cyclic AMP caused by exposure to an intermediate concentration of glucagon. No inhibition of adenylate cyclase by insulin can be shown. Basal gluconeogenesis is not significantly depressed by calcium deficiency but stimulation by glucagon is reduced by 50%. Calcium deficiency does not reduce accumulation of cyclic AMP in response to glucagon but diminishes stimulation of gluconeogenesis by exogenous cyclic AMP. Glucagon has a rapid stimulatory effect on the flux of 45Ca2+ from medium to tissue."} {"id": "PMID:169238", "title": "Effect of denaturation on the susceptibility of proteins to enzymic phosphorylation.", "content": "Heat-denatured chicken egg white lysozyme and the reduced carboxymethylated maleylated derivative of this protein were found to serve as substrates for rabbit skeletal muscle cyclic AMP-dependent protein kinase. The native form of the protein was not a substrate. Two phosphoryl groups per mole of lysozyme were incorporated in the reaction. It was determined that the phosphoryl moieties were bound to serine 24 and serine 50 in the modified protein. Serine 24 was phosphorylated approximately 3 times as fast as serine 50. Reduced carboxymethylated maleylated derivatives of bovine serum albumin, phosphorylase b, and creatine kinase also served as substrates for the protein kinase whereas their native forms did not. The reduced carboxymethylated maleylated derivative of the inhibitory subunit of troponin was a poorer substrate than the native form of the protein. Maleylated histones F1 and F2b were also poorer substrates than the nonderivatized forms. The significance of these experiments with reference to the specificity of cyclic AMP-dependent protein kinase is discussed.", "contents": "Effect of denaturation on the susceptibility of proteins to enzymic phosphorylation. Heat-denatured chicken egg white lysozyme and the reduced carboxymethylated maleylated derivative of this protein were found to serve as substrates for rabbit skeletal muscle cyclic AMP-dependent protein kinase. The native form of the protein was not a substrate. Two phosphoryl groups per mole of lysozyme were incorporated in the reaction. It was determined that the phosphoryl moieties were bound to serine 24 and serine 50 in the modified protein. Serine 24 was phosphorylated approximately 3 times as fast as serine 50. Reduced carboxymethylated maleylated derivatives of bovine serum albumin, phosphorylase b, and creatine kinase also served as substrates for the protein kinase whereas their native forms did not. The reduced carboxymethylated maleylated derivative of the inhibitory subunit of troponin was a poorer substrate than the native form of the protein. Maleylated histones F1 and F2b were also poorer substrates than the nonderivatized forms. The significance of these experiments with reference to the specificity of cyclic AMP-dependent protein kinase is discussed."} {"id": "PMID:169239", "title": "Studies of individual carbon sites of proteins in solution by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Relaxation behavior.", "content": "The aromatic regions in proton-decoupled natural abundance 13C Fourier transform nuclear magnetic resonance spectra (at 14.2 kG) of small native proteins contain broad methine carbon bands and narrow nonprotonated carbon resonances. Some factors that affect the use of natural abundance 13C Fourier transform NMR spectroscopy for monitoring individual nonprotonated aromatic carbon sites of native proteins in solution are discussed. The effect of protein size is evaluated by comparing the 13C NMR spectra of horse heart ferrocytochrome c, hen egg white lysozyme, horse carbon monoxide myoglobin, and human adult carbon monoxide hemoglobin. Numerous single carbon resonances are observed in the aromatic regions of 13C NMR spectra of cytochrome c, lysozyme, and myoglobin. The much larger hemoglobin yields few resolved individual carbon resonances. Theoretical and some experimental values are presented for the natural linewidths (W), spin-lattice relaxation times (T1), and nuclear Overhauser enhancements (NOE) of nonprotonated aromatic carbons and Czeta of arginine residues. In general, the 13C-1H dipolar mechanism dominates the relaxation of these carbons. 13C-14N dipolar relaxation contributes significantly to 1/T1 of C epsilon2 of tryptophan residues and Czeta of arginine residues of proteins in D2O. The NOE of each nonprotonated aromatic carbon is within experimental error of the calculated value of about 1.2. As a result, integrated intensities can be used for making a carbon count. Theoretical results are presented for the effect of internal rotation on W, T1, and the NOE. A comparison with the experimental T1 and NOE values indicates that if there is internal rotation of aromatic amino acid side chains, it is not fast relative to the over-all rotational motion of the protein.", "contents": "Studies of individual carbon sites of proteins in solution by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Relaxation behavior. The aromatic regions in proton-decoupled natural abundance 13C Fourier transform nuclear magnetic resonance spectra (at 14.2 kG) of small native proteins contain broad methine carbon bands and narrow nonprotonated carbon resonances. Some factors that affect the use of natural abundance 13C Fourier transform NMR spectroscopy for monitoring individual nonprotonated aromatic carbon sites of native proteins in solution are discussed. The effect of protein size is evaluated by comparing the 13C NMR spectra of horse heart ferrocytochrome c, hen egg white lysozyme, horse carbon monoxide myoglobin, and human adult carbon monoxide hemoglobin. Numerous single carbon resonances are observed in the aromatic regions of 13C NMR spectra of cytochrome c, lysozyme, and myoglobin. The much larger hemoglobin yields few resolved individual carbon resonances. Theoretical and some experimental values are presented for the natural linewidths (W), spin-lattice relaxation times (T1), and nuclear Overhauser enhancements (NOE) of nonprotonated aromatic carbons and Czeta of arginine residues. In general, the 13C-1H dipolar mechanism dominates the relaxation of these carbons. 13C-14N dipolar relaxation contributes significantly to 1/T1 of C epsilon2 of tryptophan residues and Czeta of arginine residues of proteins in D2O. The NOE of each nonprotonated aromatic carbon is within experimental error of the calculated value of about 1.2. As a result, integrated intensities can be used for making a carbon count. Theoretical results are presented for the effect of internal rotation on W, T1, and the NOE. A comparison with the experimental T1 and NOE values indicates that if there is internal rotation of aromatic amino acid side chains, it is not fast relative to the over-all rotational motion of the protein."} {"id": "PMID:169240", "title": "Studies of individual carbon sites of proteins in solution by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Strategies for assignments.", "content": "Natural abundance 13C Fourier transform NMR spectra (at 15.18 MHz, in 20-mm sample tubes) of aqueous native proteins yield numerous narrow single carbon resonances of nonprotonated aromatic carbons. Techniques for the assignment of these resonances are presented. Each technique is applied to one or more of the following proteins: ferricytochrome c from horse heart and Candida krusei, ferrocytochrome c and cyanoferricytochrome c from horse heart, lysozyme from hen egg white, cyanoferrimyoglobins from horse and sperm whale skeletal muscle, and carbon monoxide myoglobin from horse. In all of the protein spectra we have examined, methine aromatic carbons give rise to broad bands. Studies of the narrow resonances of nonprotonated aromatic carbons of proteins are facilitated by removal of these broad bands by means of the convolution-difference method, preferably from spectra recorded under conditions of noise-modulated off-resonance proton decoupling. We present a summary of the chemical shift ranges for the various types of nonprotonated aromatic carbons of amino acid residues and hemes of diamagnetic proteins, based on our results for hen egg white lysozyme, horse heart ferrocytochrome c, horse carbon monoxide myoglobin, and carbon monoxide hemoglobins from various species...", "contents": "Studies of individual carbon sites of proteins in solution by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Strategies for assignments. Natural abundance 13C Fourier transform NMR spectra (at 15.18 MHz, in 20-mm sample tubes) of aqueous native proteins yield numerous narrow single carbon resonances of nonprotonated aromatic carbons. Techniques for the assignment of these resonances are presented. Each technique is applied to one or more of the following proteins: ferricytochrome c from horse heart and Candida krusei, ferrocytochrome c and cyanoferricytochrome c from horse heart, lysozyme from hen egg white, cyanoferrimyoglobins from horse and sperm whale skeletal muscle, and carbon monoxide myoglobin from horse. In all of the protein spectra we have examined, methine aromatic carbons give rise to broad bands. Studies of the narrow resonances of nonprotonated aromatic carbons of proteins are facilitated by removal of these broad bands by means of the convolution-difference method, preferably from spectra recorded under conditions of noise-modulated off-resonance proton decoupling. We present a summary of the chemical shift ranges for the various types of nonprotonated aromatic carbons of amino acid residues and hemes of diamagnetic proteins, based on our results for hen egg white lysozyme, horse heart ferrocytochrome c, horse carbon monoxide myoglobin, and carbon monoxide hemoglobins from various species..."} {"id": "PMID:169241", "title": "Purification of cerebral glucose-6-phosphatase. An enzyme involved in sleep.", "content": "An insoluble phosphoprotein of rat brain acquires radioactivity from inorganic phosphate more rapidly during sleep than during wakefulness. It was purified in two ways. The first was solvent delipidation of brain tissue followed by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis. The second was sucrose gradient centrifugation of a brain homogenate to remove myelin, and gel filtration on Sephadex G-100 and adsorption chromatography on DEAE-Sephadex in the presence of sodium deoxycholate. The products were homogeneous within the limits of the analytical methods used. The apparent molecular weight of the phosphoprotein was 28,000 on sodium dodecyl sulfate polyacrylamide gels, but was much higher in the presence of sodium deoxycholate. The protein had a high content of aspartic and glutamic acids compared to basic amino acids. Analysis of a base hydrolysate, as well as studies of the kinetics of hydrolysis, showed that the radioactive phosphorus was attached to histidine. The NH2-terminal residue was identified as isoleucine. The phosphoprotein purified by the second method was enzymatically active. When it was incubated in vitro with a 32P-labeled supernatant fraction from rat brain (and later with glucose [6-32P]phosphate), a radioactive phosphorylated protein intermediate was formed. Exploration of the several enzymatic activities of the preparation indicated close correspondence to those reported for the glucose-6-phosphatases of liver and kidney. Glucose-6-phosphatase activity was found in all parts of the brain in the membranous subcellular fractions of neurons. It was shown to be co-purified with the sleep-related phosphoprotein. This report constitutes, we believe, the first complete purification of glucose-6-phosphatase from any tissue and an instance in which a change in the state of a cerebral enzyme has been linked to a normal change in the physiological state of the brain.", "contents": "Purification of cerebral glucose-6-phosphatase. An enzyme involved in sleep. An insoluble phosphoprotein of rat brain acquires radioactivity from inorganic phosphate more rapidly during sleep than during wakefulness. It was purified in two ways. The first was solvent delipidation of brain tissue followed by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis. The second was sucrose gradient centrifugation of a brain homogenate to remove myelin, and gel filtration on Sephadex G-100 and adsorption chromatography on DEAE-Sephadex in the presence of sodium deoxycholate. The products were homogeneous within the limits of the analytical methods used. The apparent molecular weight of the phosphoprotein was 28,000 on sodium dodecyl sulfate polyacrylamide gels, but was much higher in the presence of sodium deoxycholate. The protein had a high content of aspartic and glutamic acids compared to basic amino acids. Analysis of a base hydrolysate, as well as studies of the kinetics of hydrolysis, showed that the radioactive phosphorus was attached to histidine. The NH2-terminal residue was identified as isoleucine. The phosphoprotein purified by the second method was enzymatically active. When it was incubated in vitro with a 32P-labeled supernatant fraction from rat brain (and later with glucose [6-32P]phosphate), a radioactive phosphorylated protein intermediate was formed. Exploration of the several enzymatic activities of the preparation indicated close correspondence to those reported for the glucose-6-phosphatases of liver and kidney. Glucose-6-phosphatase activity was found in all parts of the brain in the membranous subcellular fractions of neurons. It was shown to be co-purified with the sleep-related phosphoprotein. This report constitutes, we believe, the first complete purification of glucose-6-phosphatase from any tissue and an instance in which a change in the state of a cerebral enzyme has been linked to a normal change in the physiological state of the brain."} {"id": "PMID:169242", "title": "Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity.", "content": "The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3'-mono-than 3',5'-di-substituted iodothyronines. A 4'-hydroxyl group is essential, but the 3' substituent can be several halogen or non-halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen-free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites.", "contents": "Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity. The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3'-mono-than 3',5'-di-substituted iodothyronines. A 4'-hydroxyl group is essential, but the 3' substituent can be several halogen or non-halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen-free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites."} {"id": "PMID:169243", "title": "The mechanism of action of cholera toxin in pigeon erythrocyte lysates.", "content": "The adenylate cyclase activity of intact pigeon erythrocytes begins to rise after about 20 min of exposure to cholera toxin. The maximum rate at which the cyclase activity increases appears to be limited by the number of toxin molecules which can reach an intracellular target. If the erythrocytes are made permeable to the toxin by a bacterial hemolysin, no such limit exists, and adenylate cyclase activity starts to rise immediately upon the addition of toxin, and continues to rise to a maximum at an initially constant rate which is dependent upon the concentration of toxin. On lysed erythrocytes, the addition of cholera antitoxin immediately prevents any further rise in adenylate cyclase activity, but does not reverse any activation already achieved. Erythrocyte lysates may also be activated by isolated peptide A1 of cholera toxin, although activation of adenylate cyclase of intact erythrocytes requires the complete toxin molecule. In the intact cells, toxin first attaches by its Component B to surface receptors of which there are about 30 per erythrocyte. Subsequently, peptide A1 but not Component B is inserted into the erythrocyte. It takes only about 1 min at 37 degrees for peptide A1 to be sufficiently deep within the cell membrane to be inaccessible to extracellular antitoxin, but its complete transit through the membrane appears to take longer. The surface receptors are used only once, for they remain blocked by Component B. The number of receptors available on the surface may be increased by soaking cells in ganglioside GM1. Cholera toxin also decreases the rate of apparently spontaneous loss of adenylate cyclase activity and increases the response to epinephrine. Theophylline inhibits the action of cholera toxin.", "contents": "The mechanism of action of cholera toxin in pigeon erythrocyte lysates. The adenylate cyclase activity of intact pigeon erythrocytes begins to rise after about 20 min of exposure to cholera toxin. The maximum rate at which the cyclase activity increases appears to be limited by the number of toxin molecules which can reach an intracellular target. If the erythrocytes are made permeable to the toxin by a bacterial hemolysin, no such limit exists, and adenylate cyclase activity starts to rise immediately upon the addition of toxin, and continues to rise to a maximum at an initially constant rate which is dependent upon the concentration of toxin. On lysed erythrocytes, the addition of cholera antitoxin immediately prevents any further rise in adenylate cyclase activity, but does not reverse any activation already achieved. Erythrocyte lysates may also be activated by isolated peptide A1 of cholera toxin, although activation of adenylate cyclase of intact erythrocytes requires the complete toxin molecule. In the intact cells, toxin first attaches by its Component B to surface receptors of which there are about 30 per erythrocyte. Subsequently, peptide A1 but not Component B is inserted into the erythrocyte. It takes only about 1 min at 37 degrees for peptide A1 to be sufficiently deep within the cell membrane to be inaccessible to extracellular antitoxin, but its complete transit through the membrane appears to take longer. The surface receptors are used only once, for they remain blocked by Component B. The number of receptors available on the surface may be increased by soaking cells in ganglioside GM1. Cholera toxin also decreases the rate of apparently spontaneous loss of adenylate cyclase activity and increases the response to epinephrine. Theophylline inhibits the action of cholera toxin."} {"id": "PMID:169244", "title": "Interaction of the estradiol receptor from calf uterus with its nuclear acceptor sites.", "content": "The specific interaction between 17 beta-estradiol-receptor complex and nuclear acceptors was analyzed by immobilizing various nuclear proteins to CNBr-activated agarose. The specific, high affinity sites identified in a fraction of basic proteins that can be solubilized from purified nuclei of calf uterus (Puca, G.A., Sica, V., and Nola. E (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 979-983) were chromatographed on Sephadex G-100 columns. Elution of the acceptor activity depends on the pH and ionic strength of the buffer used. With 5 mM HCl, however, a peak of acceptor activity with a molecular weight of about 70,000 was partially dissociated from the other basic nuclear proteins. The high affinity binding of the receptor to the acceptor proteins was estradiol-, but not progesterone-, cortisone-, or testosterone-dependent; it was very sensitive to ionic strength and showed a physiological pH optimum. Low affinity binding, such as that seen between receptor and histone, showed no estradiol dependence and little ionic strength and pH sensitivity. Native or heat-denatured DNA strongly modified the receptor-acceptor interaction, reducing the number of binding sites of acceptor for the receptor without changing the high affinity of the interaction. Heating of the acceptor protein before its covalent linkage to agarose considerably increased the affinity of the resulting agarose derivative. Free sulfhydryl groups of the receptor but not of the acceptor molecule play an important role in the acceptor-receptor interaction. When receptor and acceptor preparations were incubated in solution, the resulting complex was included on a Sephadex G-100 column and it eluted from DEAE-cellulose columns at lower ionic strength than the receptor alone. Even though not absolutely specific, these two properties allowed determination of the molecular weight (85,000) of the acceptor protein at neutral pH and more nearly physiological ionic strength. The apparent KD of the acceptor-receptor interaction was determined to be 2 x 10(-10) M at O degrees. Apparently similar, high affinity binding sites for estradiol receptors are also present in nuclei of other tissues.", "contents": "Interaction of the estradiol receptor from calf uterus with its nuclear acceptor sites. The specific interaction between 17 beta-estradiol-receptor complex and nuclear acceptors was analyzed by immobilizing various nuclear proteins to CNBr-activated agarose. The specific, high affinity sites identified in a fraction of basic proteins that can be solubilized from purified nuclei of calf uterus (Puca, G.A., Sica, V., and Nola. E (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 979-983) were chromatographed on Sephadex G-100 columns. Elution of the acceptor activity depends on the pH and ionic strength of the buffer used. With 5 mM HCl, however, a peak of acceptor activity with a molecular weight of about 70,000 was partially dissociated from the other basic nuclear proteins. The high affinity binding of the receptor to the acceptor proteins was estradiol-, but not progesterone-, cortisone-, or testosterone-dependent; it was very sensitive to ionic strength and showed a physiological pH optimum. Low affinity binding, such as that seen between receptor and histone, showed no estradiol dependence and little ionic strength and pH sensitivity. Native or heat-denatured DNA strongly modified the receptor-acceptor interaction, reducing the number of binding sites of acceptor for the receptor without changing the high affinity of the interaction. Heating of the acceptor protein before its covalent linkage to agarose considerably increased the affinity of the resulting agarose derivative. Free sulfhydryl groups of the receptor but not of the acceptor molecule play an important role in the acceptor-receptor interaction. When receptor and acceptor preparations were incubated in solution, the resulting complex was included on a Sephadex G-100 column and it eluted from DEAE-cellulose columns at lower ionic strength than the receptor alone. Even though not absolutely specific, these two properties allowed determination of the molecular weight (85,000) of the acceptor protein at neutral pH and more nearly physiological ionic strength. The apparent KD of the acceptor-receptor interaction was determined to be 2 x 10(-10) M at O degrees. Apparently similar, high affinity binding sites for estradiol receptors are also present in nuclei of other tissues."} {"id": "PMID:169245", "title": "Inhibition of basal and hormone-stimulated adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide prostaglandin H2.", "content": "The prostaglandin endoperoxide PGH2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid), at a concentration of 2.8 x 10(-5) M inhibited basal adenylate cyclase activity 11% and epinephrine-stimulated activity 30 to 35%. PGH2 inhibited epinephrine-stimulated enzyme activity in the presence of 10 mM theophylline, 2.5 mM adenosine 3':5'-monophosphate (cAMP), or in the absence of inhibitors or substrates of the cAMP phosphodiesterase. When the cAMP phosphodiesterase was assayed directly using 62 nM and 1.1 muM cAMP, PGH2 did not affect the 100,000 x g particulate cAMP phosphodiesterase from fat cells. The inhibition of adenylate cyclase by PGH2 was readily reversible. A 6-min preincubation of ghost membranes with PGH2, followed by washing, did not alter subsequent epinephrine-stimulated adenylate cyclase activity. During epinephrine stimulation, the PGH2 inhibition was apparent on initial rates of cAMP synthesis, and the addition of PGH2 to the enzyme system at any point during an assay markedly reduced the rate of cAMP synthesis. Between 2.8 x 10(-7) M and 2.8 x 10(-5) M, PGH2 inhibited epinephrine-stimulated enzyme activity in a concentration-dependent manner. The stimulation of adenylate cyclase by thyroid-stimulating hormone, glucagon, and adrenocorticotropic hormone as well as by epinephrine was antagonized by PGH2, suggesting that PGH2 may be an endogenous feedback regulator of hormone-stimulated lipolysis in adipose tissue.", "contents": "Inhibition of basal and hormone-stimulated adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide prostaglandin H2. The prostaglandin endoperoxide PGH2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid), at a concentration of 2.8 x 10(-5) M inhibited basal adenylate cyclase activity 11% and epinephrine-stimulated activity 30 to 35%. PGH2 inhibited epinephrine-stimulated enzyme activity in the presence of 10 mM theophylline, 2.5 mM adenosine 3':5'-monophosphate (cAMP), or in the absence of inhibitors or substrates of the cAMP phosphodiesterase. When the cAMP phosphodiesterase was assayed directly using 62 nM and 1.1 muM cAMP, PGH2 did not affect the 100,000 x g particulate cAMP phosphodiesterase from fat cells. The inhibition of adenylate cyclase by PGH2 was readily reversible. A 6-min preincubation of ghost membranes with PGH2, followed by washing, did not alter subsequent epinephrine-stimulated adenylate cyclase activity. During epinephrine stimulation, the PGH2 inhibition was apparent on initial rates of cAMP synthesis, and the addition of PGH2 to the enzyme system at any point during an assay markedly reduced the rate of cAMP synthesis. Between 2.8 x 10(-7) M and 2.8 x 10(-5) M, PGH2 inhibited epinephrine-stimulated enzyme activity in a concentration-dependent manner. The stimulation of adenylate cyclase by thyroid-stimulating hormone, glucagon, and adrenocorticotropic hormone as well as by epinephrine was antagonized by PGH2, suggesting that PGH2 may be an endogenous feedback regulator of hormone-stimulated lipolysis in adipose tissue."} {"id": "PMID:169246", "title": "Synthesis and study of the estrogenic activity of 2,4-bis(bromomethyl)estradiol-17 beta 3-methyl ether.", "content": "Synthesis of 2,4-bis(bromomethyl)estradiol-17 beta 3-methyl ether (BBE2M) was accomplished by reducing a methanolic solution of 2,4-bis(bromomethyl)estrone methyl ether with sodium borohydride. In 0.5 M phosphate buffer, pH 7.0, 25 degrees, BBE2M readily reacts with Ellman's anion and alkylates cysteine to form a steroid-amino acid conjugate. Stoichiometry of the reaction indicates that the bromosteroid is divalent with cysteine. Tryptophan and histidine react more slowly with the bromosteroid. Estrogenic activity of BBE2M was evaluated in ovariectomized rats by uterine intraluminal administration and quantitation of glucose-6-phosphate dehydrogenase (D-glucose-6-P:NADP+ oxidoreductase, EC 1.1.1.49) activity in the uterus. BBE2M induced glucose-6-phosphate dehydrogenase activity as did estradiol-17 beta or estradiol-17 beta 3-methyl ether (E2M). BBE2M was more persistent in activity than E2M. Histological examination of uterus following BBE2M treatment shows classic estrogenic morphology. BBE2M covalently binds to the cytoplasmic estrogen receptor of calf uterus. Such binding is prevented by pretreatment of the receptor protein with estradiol-17 beta. The covalently bound steroid-receptor complex appears to stimulate RNA synthesis in isolated nuclei from calf endometrium.", "contents": "Synthesis and study of the estrogenic activity of 2,4-bis(bromomethyl)estradiol-17 beta 3-methyl ether. Synthesis of 2,4-bis(bromomethyl)estradiol-17 beta 3-methyl ether (BBE2M) was accomplished by reducing a methanolic solution of 2,4-bis(bromomethyl)estrone methyl ether with sodium borohydride. In 0.5 M phosphate buffer, pH 7.0, 25 degrees, BBE2M readily reacts with Ellman's anion and alkylates cysteine to form a steroid-amino acid conjugate. Stoichiometry of the reaction indicates that the bromosteroid is divalent with cysteine. Tryptophan and histidine react more slowly with the bromosteroid. Estrogenic activity of BBE2M was evaluated in ovariectomized rats by uterine intraluminal administration and quantitation of glucose-6-phosphate dehydrogenase (D-glucose-6-P:NADP+ oxidoreductase, EC 1.1.1.49) activity in the uterus. BBE2M induced glucose-6-phosphate dehydrogenase activity as did estradiol-17 beta or estradiol-17 beta 3-methyl ether (E2M). BBE2M was more persistent in activity than E2M. Histological examination of uterus following BBE2M treatment shows classic estrogenic morphology. BBE2M covalently binds to the cytoplasmic estrogen receptor of calf uterus. Such binding is prevented by pretreatment of the receptor protein with estradiol-17 beta. The covalently bound steroid-receptor complex appears to stimulate RNA synthesis in isolated nuclei from calf endometrium."} {"id": "PMID:169247", "title": "Singlet oxygen production associated with enzyme-catalyzed lipid peroxidation in liver microsomes.", "content": "Evidence for the formation of singlet oxygen during the oxidation of NADPH by liver microsomes is presented. The evidence is based primarily on the enzyme-dependent formation of dibenzoylethylene from diphenylfuran, a reaction which is specific for singlet oxygen. The apparent formation of singlet oxygen is coupled to the occurrence of peroxidation of microsomal lipid, a phenomenon known to be associated with NADPH oxidation by the particles. Both the peroxidation of lipid and the apparent formation of singlet oxygen are related to the amount of Fe3+ present in the system and the results are consistent with the possibility that the singlet oxygen formed by this system is derived from the breakdown of lipid peroxides. If 1O2 is formed from breakdown of lipid peroxides, it would be dependent on O-/-2 formation because superoxide anion has been shown to undergo reactions in this system which generate extremely reactive free radicals (probably hydroxyl) that initiate lipid peroxidation. These peroxides are quite unstable and their degradation may be the source of 1O2. We have consistently observed that O-/-2 itself is not a reactive radical with respect to lipids or radical scavengers. Hence, O-/-2 cannot be the radical which initiates lipid peroxidation on which 1O2 generation appears to depend. The results may offer at least part of the explanation for the dietary requirement for alpha-tocopherol which not only scavenges free radicals but quenches singlet oxygen as well. This report also includes description of studies indicating that another enzyme, xanthine oxidase, which forms superoxide anion during its activity under aerobic conditions, does not form singlet oxygen during its function. This finding is in contrast to reports of others which indicate that xanthine oxidase activity does produce 1O2.", "contents": "Singlet oxygen production associated with enzyme-catalyzed lipid peroxidation in liver microsomes. Evidence for the formation of singlet oxygen during the oxidation of NADPH by liver microsomes is presented. The evidence is based primarily on the enzyme-dependent formation of dibenzoylethylene from diphenylfuran, a reaction which is specific for singlet oxygen. The apparent formation of singlet oxygen is coupled to the occurrence of peroxidation of microsomal lipid, a phenomenon known to be associated with NADPH oxidation by the particles. Both the peroxidation of lipid and the apparent formation of singlet oxygen are related to the amount of Fe3+ present in the system and the results are consistent with the possibility that the singlet oxygen formed by this system is derived from the breakdown of lipid peroxides. If 1O2 is formed from breakdown of lipid peroxides, it would be dependent on O-/-2 formation because superoxide anion has been shown to undergo reactions in this system which generate extremely reactive free radicals (probably hydroxyl) that initiate lipid peroxidation. These peroxides are quite unstable and their degradation may be the source of 1O2. We have consistently observed that O-/-2 itself is not a reactive radical with respect to lipids or radical scavengers. Hence, O-/-2 cannot be the radical which initiates lipid peroxidation on which 1O2 generation appears to depend. The results may offer at least part of the explanation for the dietary requirement for alpha-tocopherol which not only scavenges free radicals but quenches singlet oxygen as well. This report also includes description of studies indicating that another enzyme, xanthine oxidase, which forms superoxide anion during its activity under aerobic conditions, does not form singlet oxygen during its function. This finding is in contrast to reports of others which indicate that xanthine oxidase activity does produce 1O2."} {"id": "PMID:169248", "title": "Thyrotropin receptors in thyroid plasma membranes. Characteristics of thyrotropin binding and solubilization of thyrotropin receptor activity by tryptic digestion.", "content": "Biologically active bovine 125I-thyrotropin preparations have been prepared, characterized, and used to evaluate the optimal conditions for thyrotropin binding to bovine thyroid plasma membranes in vitro. Binding of 125I-TSH has a pH optimum around 6.0 and is sensitive to the choice and concentration of buffer. Binding is inhibited by salts, especially those containing magnesium and calcium ions; magnesium concentrations optimal for adenylate cyclase assays (2 to 5 mM) result in 85 to 98% inhibition of binding. Binding is temperature sensitive. At 37 degrees binding has its highest initial level; however, instability of the membrane at this temperature causes a rapid loss of binding activity. Binding at 0 degrees is optimal in 30 min and at the same level as initial binding at 37 degrees; since there is no decrease in binding activity, it has been chosen as the optimal temperature. Thyrotropin, luteinizing hormone, the beta subunit of thyrotropin, and the alpha subunit of thyrotropin have relative binding affinities for the thyrotropin receptors of 100, 10, 2, and less than 0.5, respectively. In all of these characteristics, 125I-thyrotropin at 1.5 x 10(-5) M concentrations has the same properties of binding to bovine plasma membranes as do [3H]thyrotropin preparations which have been previously characterized (Amir, S.M., Carraway, T.F., Jr., Kohn, L.D., and Winand, R.V. (1973) J. Biol. Chem. 248, 4092-4100) and used to study binding at 5 x 10(-6) M concentrations. 125I-TSH binding as a function of hormone concentration results in curved Scatchard plots; however, Hill plots of these same binding data are linear and have a slope of 0.65. Taken together, these data suggest that the heterogeneity in thyrotropin binding constants which is evident in the Scatchard plot reflects a negatively cooperative relationship among the thyrotropin receptor sites, i.e. decreased hormonal affinity as hormone concentrations increase. Adenylate cyclase studies yield kinetic plots which also exhibit negative cooperativity; corrections for thyrotropin bound under the adverse binding conditions of the adenylate cyclase assays suggest that Km values for thyrotropin in this enzymatic assay are compatible with binding constants measured by the 125I-thyrotropin preparations. Tryptic digestion destroys binding activity on the thyroid plasma membrane but releases specific thyrotropin receptor activity into the supernatant phase. Chromatography on Sephadex G-100 indicates that this solubilized receptor fragment has a molecular weight between 15,000 and 30,000.", "contents": "Thyrotropin receptors in thyroid plasma membranes. Characteristics of thyrotropin binding and solubilization of thyrotropin receptor activity by tryptic digestion. Biologically active bovine 125I-thyrotropin preparations have been prepared, characterized, and used to evaluate the optimal conditions for thyrotropin binding to bovine thyroid plasma membranes in vitro. Binding of 125I-TSH has a pH optimum around 6.0 and is sensitive to the choice and concentration of buffer. Binding is inhibited by salts, especially those containing magnesium and calcium ions; magnesium concentrations optimal for adenylate cyclase assays (2 to 5 mM) result in 85 to 98% inhibition of binding. Binding is temperature sensitive. At 37 degrees binding has its highest initial level; however, instability of the membrane at this temperature causes a rapid loss of binding activity. Binding at 0 degrees is optimal in 30 min and at the same level as initial binding at 37 degrees; since there is no decrease in binding activity, it has been chosen as the optimal temperature. Thyrotropin, luteinizing hormone, the beta subunit of thyrotropin, and the alpha subunit of thyrotropin have relative binding affinities for the thyrotropin receptors of 100, 10, 2, and less than 0.5, respectively. In all of these characteristics, 125I-thyrotropin at 1.5 x 10(-5) M concentrations has the same properties of binding to bovine plasma membranes as do [3H]thyrotropin preparations which have been previously characterized (Amir, S.M., Carraway, T.F., Jr., Kohn, L.D., and Winand, R.V. (1973) J. Biol. Chem. 248, 4092-4100) and used to study binding at 5 x 10(-6) M concentrations. 125I-TSH binding as a function of hormone concentration results in curved Scatchard plots; however, Hill plots of these same binding data are linear and have a slope of 0.65. Taken together, these data suggest that the heterogeneity in thyrotropin binding constants which is evident in the Scatchard plot reflects a negatively cooperative relationship among the thyrotropin receptor sites, i.e. decreased hormonal affinity as hormone concentrations increase. Adenylate cyclase studies yield kinetic plots which also exhibit negative cooperativity; corrections for thyrotropin bound under the adverse binding conditions of the adenylate cyclase assays suggest that Km values for thyrotropin in this enzymatic assay are compatible with binding constants measured by the 125I-thyrotropin preparations. Tryptic digestion destroys binding activity on the thyroid plasma membrane but releases specific thyrotropin receptor activity into the supernatant phase. Chromatography on Sephadex G-100 indicates that this solubilized receptor fragment has a molecular weight between 15,000 and 30,000."} {"id": "PMID:169249", "title": "Characteristics of a solubilized thyrotropin receptor from bovine thyroid plasma membranes.", "content": "The thyrotropin receptor from bovine thyroid plasma membranes has been solubilized using lithium diiodosalicylate, and an assay to measure thyrotropin binding to the solubilized receptor has been developed. Both the solubilized thyrotropin receptor and the thyrotropin receptor on thyroid plasma membranes have effectively identical nonlinear Scatchard plots and negatively sloped Hill plots, i.e. both preparations have receptors which appear to exhibit a similar negatively cooperative relationship. Although the pH optimum of thyrotropin binding to the solubilized receptor is the same as that of the thyroid plasma membrane receptor, pH 6.0, the pH dependency curve of the solubilized receptor is slightly different in its outline. Thyrotropin binding to the solubilized receptor is less sensitive to salt inhibition than is binding to the thyroid plasma membrane receptor; however, optimal binding remains at 0 degrees. The relative affinities of thyrotropin and two glycoprotein hormones which can be considered structural analogs, luteinizing hormone and human chorionic gonadotropin, are 100:10:5, respectively, toward plasma membrane receptors, but 100:25:40 toward the solubilized receptors. The solubilized receptor preparation is heterogeneous in size in that it has binding components with molecular weights of 286,000, 160,000, 75,000, and 15,000 to 30,000. Tryptic digestion converts all three higher molecular weight components to the 15,000 to 30,000 molecular weight species, and the 15,000 to 30,000 molecular weight receptor component has all of the binding properties of the solubilized receptor preparation before tryptic digestion including an identical nonlinear Scatchard plot. It has the same size as and coelutes from Sephadex G-100 with a 15,000 to 30,000 molecular weight receptor released by tryptic digestion of bovine thyroid plasma membranes or tryptic digestion of bovine or dog thyroid cells in culture. The tryptic fragment of the solubilized receptor or preparations has been purified almost 250-fold by affinity chromatography on thyrotropin-Sepharose columns. The binding activity is lost when the solubilized thyrotropin receptor preparation is exposed to beads of neuraminidase-Sepharose or conconavalin A-Sepharose.", "contents": "Characteristics of a solubilized thyrotropin receptor from bovine thyroid plasma membranes. The thyrotropin receptor from bovine thyroid plasma membranes has been solubilized using lithium diiodosalicylate, and an assay to measure thyrotropin binding to the solubilized receptor has been developed. Both the solubilized thyrotropin receptor and the thyrotropin receptor on thyroid plasma membranes have effectively identical nonlinear Scatchard plots and negatively sloped Hill plots, i.e. both preparations have receptors which appear to exhibit a similar negatively cooperative relationship. Although the pH optimum of thyrotropin binding to the solubilized receptor is the same as that of the thyroid plasma membrane receptor, pH 6.0, the pH dependency curve of the solubilized receptor is slightly different in its outline. Thyrotropin binding to the solubilized receptor is less sensitive to salt inhibition than is binding to the thyroid plasma membrane receptor; however, optimal binding remains at 0 degrees. The relative affinities of thyrotropin and two glycoprotein hormones which can be considered structural analogs, luteinizing hormone and human chorionic gonadotropin, are 100:10:5, respectively, toward plasma membrane receptors, but 100:25:40 toward the solubilized receptors. The solubilized receptor preparation is heterogeneous in size in that it has binding components with molecular weights of 286,000, 160,000, 75,000, and 15,000 to 30,000. Tryptic digestion converts all three higher molecular weight components to the 15,000 to 30,000 molecular weight species, and the 15,000 to 30,000 molecular weight receptor component has all of the binding properties of the solubilized receptor preparation before tryptic digestion including an identical nonlinear Scatchard plot. It has the same size as and coelutes from Sephadex G-100 with a 15,000 to 30,000 molecular weight receptor released by tryptic digestion of bovine thyroid plasma membranes or tryptic digestion of bovine or dog thyroid cells in culture. The tryptic fragment of the solubilized receptor or preparations has been purified almost 250-fold by affinity chromatography on thyrotropin-Sepharose columns. The binding activity is lost when the solubilized thyrotropin receptor preparation is exposed to beads of neuraminidase-Sepharose or conconavalin A-Sepharose."} {"id": "PMID:169250", "title": "Thyrotropin effects on thyroid cells in culture. Effects of trypsin on the thyrotropin receptor and on thyrotropin-mediated cyclic 3':5'-AMP changes.", "content": "Dog, human, and bovine thyroid cells in culture have been shown to develop follicle-like structures when cells are cultured in conditions of confluency and when cells are incubated in the presence of bovine thyrotropin or N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate during the first 24 to 48 hours after trypsinization. If thyrotropin is added 48 hours after trypsinization, these cells do not form follicle-like structures but remain as a monolayer culture. Although thyroid cells which grow as a monolayer have a thyrotropin receptor on their plasma membranes with the same in vitro binding properties as the thyrotropin receptor on the plasma membranes of the follicle-forming thyroid cells, there is a 1- to 2-fold greater number of receptors per mg of membrane protein when follicle-forming and monolayer cultures are compared...", "contents": "Thyrotropin effects on thyroid cells in culture. Effects of trypsin on the thyrotropin receptor and on thyrotropin-mediated cyclic 3':5'-AMP changes. Dog, human, and bovine thyroid cells in culture have been shown to develop follicle-like structures when cells are cultured in conditions of confluency and when cells are incubated in the presence of bovine thyrotropin or N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate during the first 24 to 48 hours after trypsinization. If thyrotropin is added 48 hours after trypsinization, these cells do not form follicle-like structures but remain as a monolayer culture. Although thyroid cells which grow as a monolayer have a thyrotropin receptor on their plasma membranes with the same in vitro binding properties as the thyrotropin receptor on the plasma membranes of the follicle-forming thyroid cells, there is a 1- to 2-fold greater number of receptors per mg of membrane protein when follicle-forming and monolayer cultures are compared..."} {"id": "PMID:169251", "title": "Functional arginine residues involved in coenzyme binding by glutamate dehydrogenases.", "content": "Reaction of the NADP-dependent glutamate dehydrogenase of Neurospora with 1,2-cyclohexanedione results in a biphasic loss of enzyme activity. At the end of the rapid phase of the reaction (t1/2 = 1.5 min) the enzyme activity is diminished by approximately 60% with the simultaneous loss of 1 residue of arginine per subunit. After 60 min, the enzyme activity is completely lost with the modification of a total of 2 arginine residues per subunit. Reaction of bovine liver glutamate dehydrogenase with cyclohexanedione causes a rapid loss of approximately 45% of the enzyme activity and modification of about 1.5 residues of arginine per subunit. More prolonged treatment results in reaction of an additional 4 residues of arginine per subunit but is without further effect on the residual activity. The activity of the Neurospora enzyme is not protected by substrate, coenzyme, or a combination of both; however, the activity of the bovine enzyme is partially protected by high levels of NAD or NADP. Although the Km for alpha-ketoglutarate is unchanged by a limited modification of either enzyme with cyclohexanedione, the Km for coenzyme is increased about 2-fold for the Neurospora enzyme and about 1.5-fold for the bovine enzyme. The Ki of the Neurospora dehydrogenase for the competitive inhibitor 2'-monophosphoadenosine-5'-diphosphoribose is unchanged by the enzyme modification, but nicotinamide mononucleotide, a competitive inhibitor for the native Neurospora enzyme, does not inhibit the glutamate dehydrogenase with 1 modified arginine residue. This finding implies that the modified arginine is at or near the nicotinamide binding iste of the enzyme.", "contents": "Functional arginine residues involved in coenzyme binding by glutamate dehydrogenases. Reaction of the NADP-dependent glutamate dehydrogenase of Neurospora with 1,2-cyclohexanedione results in a biphasic loss of enzyme activity. At the end of the rapid phase of the reaction (t1/2 = 1.5 min) the enzyme activity is diminished by approximately 60% with the simultaneous loss of 1 residue of arginine per subunit. After 60 min, the enzyme activity is completely lost with the modification of a total of 2 arginine residues per subunit. Reaction of bovine liver glutamate dehydrogenase with cyclohexanedione causes a rapid loss of approximately 45% of the enzyme activity and modification of about 1.5 residues of arginine per subunit. More prolonged treatment results in reaction of an additional 4 residues of arginine per subunit but is without further effect on the residual activity. The activity of the Neurospora enzyme is not protected by substrate, coenzyme, or a combination of both; however, the activity of the bovine enzyme is partially protected by high levels of NAD or NADP. Although the Km for alpha-ketoglutarate is unchanged by a limited modification of either enzyme with cyclohexanedione, the Km for coenzyme is increased about 2-fold for the Neurospora enzyme and about 1.5-fold for the bovine enzyme. The Ki of the Neurospora dehydrogenase for the competitive inhibitor 2'-monophosphoadenosine-5'-diphosphoribose is unchanged by the enzyme modification, but nicotinamide mononucleotide, a competitive inhibitor for the native Neurospora enzyme, does not inhibit the glutamate dehydrogenase with 1 modified arginine residue. This finding implies that the modified arginine is at or near the nicotinamide binding iste of the enzyme."} {"id": "PMID:169252", "title": "Free fatty acids as feedback regulators of adenylate cyclase and cyclic 3':5'-AMP accumulation in rat fat cells.", "content": "Rat fat cells incubated with lipolytic agents released substances to the medium which acted as feedback regulators of cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. The feedback regulators were not removed by adenosine deaminase. Dialyzed medium that had previously been incubated with fat cells in the presence of norepinephrine markedly inhibited cyclic AMP accumulation by fresh cells, whereas dialyzed medium from control cells did not inhibit cyclic AMP accumulation. The effects of lipolytic agents could be mimicked by adding dialyzed medium previously incubated with fat cells in the presence of oleic acid. This suggested that free fatty acids were the nondialyzable and adenosine deaminase-insensitive inhibitors of cyclic AMP accumulation released to the medium by fat cells incubated with lipolytic agents. The regulatory function of free fatty acids was related to the molar ratio of fatty acid to albumin. Profound inhibition of both lipolysis and cyclic AMP accumulation was seen as the free fatty acid/albumin ratio exceeded 3. The inhibition of cyclic AMP accumulation by oleate was seen as soon as there was a detectable increase in cyclic AMP due to lipolytic agents. Protein kinase activity (in the presence of cyclic AMP) of the infranatant obtained after centrifugation of fat cell homogenates at 48,000 x g was inhibited by medium from cells incubated with lipolytic agents or added oleate. Adenylate cyclase activity of rat fat cell ghosts was also inhibited by dialyzed or nondialyzed medium that previously had been incubated with lipolytic agents or added fatty acids. The direct addition of oleate markedly inhibited adenylate cyclase activity as the free fatty acid/albumin ratio exceeded 2. These data suggest that the prolonged drop in cyclic AMP accumulation seen during the incubation of rat fat cells with lipolytic agents is due to the inhibition of adenylate cyclase. This occurs when the free fatty acid/albumin ratio exceeds 3.", "contents": "Free fatty acids as feedback regulators of adenylate cyclase and cyclic 3':5'-AMP accumulation in rat fat cells. Rat fat cells incubated with lipolytic agents released substances to the medium which acted as feedback regulators of cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. The feedback regulators were not removed by adenosine deaminase. Dialyzed medium that had previously been incubated with fat cells in the presence of norepinephrine markedly inhibited cyclic AMP accumulation by fresh cells, whereas dialyzed medium from control cells did not inhibit cyclic AMP accumulation. The effects of lipolytic agents could be mimicked by adding dialyzed medium previously incubated with fat cells in the presence of oleic acid. This suggested that free fatty acids were the nondialyzable and adenosine deaminase-insensitive inhibitors of cyclic AMP accumulation released to the medium by fat cells incubated with lipolytic agents. The regulatory function of free fatty acids was related to the molar ratio of fatty acid to albumin. Profound inhibition of both lipolysis and cyclic AMP accumulation was seen as the free fatty acid/albumin ratio exceeded 3. The inhibition of cyclic AMP accumulation by oleate was seen as soon as there was a detectable increase in cyclic AMP due to lipolytic agents. Protein kinase activity (in the presence of cyclic AMP) of the infranatant obtained after centrifugation of fat cell homogenates at 48,000 x g was inhibited by medium from cells incubated with lipolytic agents or added oleate. Adenylate cyclase activity of rat fat cell ghosts was also inhibited by dialyzed or nondialyzed medium that previously had been incubated with lipolytic agents or added fatty acids. The direct addition of oleate markedly inhibited adenylate cyclase activity as the free fatty acid/albumin ratio exceeded 2. These data suggest that the prolonged drop in cyclic AMP accumulation seen during the incubation of rat fat cells with lipolytic agents is due to the inhibition of adenylate cyclase. This occurs when the free fatty acid/albumin ratio exceeds 3."} {"id": "PMID:169253", "title": "Lack of feedback regulation of cyclic 3':5'-AMP accumulation by free fatty acids in chicken fat cells.", "content": "Fat cells isolated from the mesenteric adipose tissue of chickens (pullets) responded to glucagon with an increase in lipolysis and a sustained rise in cyclic adenosine 3':5'-monophosphate (cyclic AMP) over a 30-min incubation. The prolonged accumulation of cyclic AMP due to glucagon in chicken fat cells was primarily intracellular. In addition, there was little increase in cyclic AMP accumulation due to theophylline alone or potentiation of the increase due to glucagon. These data indicate that chicken fat cells, unlike rat fat cells, are relatively insensitive to theophylline. Neither lipolysis nor cyclic AMP accumulation by chicken fat cells was inhibited by free fatty acid to albumin ratios (3 to 7) which markedly reduced both events in rat fat cells. However, in the absence of albumin from the medium, lipolysis in chicken fat cells was reduced, but not to the same extent as in rat fat cells. Chicken fat cells did accumulate more intracellular free fatty acids in response to lipolytic agents than did rat fat cells. The uptake of oleate by rat and chicken fat cells was identical. Glucagon-induced accumulation of cyclic AMP by chicken fat cell ghosts was unaffected by added oleate. Under identical conditions glucagon-induced adenylate cyclase activity of rat fat cell ghosts was markedly inhibited by added oleate. Triglyceride lipase activity of the pH 5.2 precipitate from a 40,000 x g infranatant of homogenized fat cells from chickens was less sensitive than that from rat fat cells to the ratio of oleate to albumin. These results suggest that the maintenance of cyclic AMP levels in chicken fat cells incubated with lipolytic agents results from the relative insensitivity of chicken fat cells to free fatty acid inhibition of cyclic AMP accumulation.", "contents": "Lack of feedback regulation of cyclic 3':5'-AMP accumulation by free fatty acids in chicken fat cells. Fat cells isolated from the mesenteric adipose tissue of chickens (pullets) responded to glucagon with an increase in lipolysis and a sustained rise in cyclic adenosine 3':5'-monophosphate (cyclic AMP) over a 30-min incubation. The prolonged accumulation of cyclic AMP due to glucagon in chicken fat cells was primarily intracellular. In addition, there was little increase in cyclic AMP accumulation due to theophylline alone or potentiation of the increase due to glucagon. These data indicate that chicken fat cells, unlike rat fat cells, are relatively insensitive to theophylline. Neither lipolysis nor cyclic AMP accumulation by chicken fat cells was inhibited by free fatty acid to albumin ratios (3 to 7) which markedly reduced both events in rat fat cells. However, in the absence of albumin from the medium, lipolysis in chicken fat cells was reduced, but not to the same extent as in rat fat cells. Chicken fat cells did accumulate more intracellular free fatty acids in response to lipolytic agents than did rat fat cells. The uptake of oleate by rat and chicken fat cells was identical. Glucagon-induced accumulation of cyclic AMP by chicken fat cell ghosts was unaffected by added oleate. Under identical conditions glucagon-induced adenylate cyclase activity of rat fat cell ghosts was markedly inhibited by added oleate. Triglyceride lipase activity of the pH 5.2 precipitate from a 40,000 x g infranatant of homogenized fat cells from chickens was less sensitive than that from rat fat cells to the ratio of oleate to albumin. These results suggest that the maintenance of cyclic AMP levels in chicken fat cells incubated with lipolytic agents results from the relative insensitivity of chicken fat cells to free fatty acid inhibition of cyclic AMP accumulation."} {"id": "PMID:169254", "title": "Purification of tryptophan transfer RNA from chick cells and its identity with \"spot 1\" RNA of Rous sarcoma virus.", "content": "Tryptophan transfer RNA from chick cells chromatographs differently in the reversed-phase column chromatographic system 5 depending upon whether it is aminoacylated or not. This property was utilized to prepare pure tryptophan tRNA. Oligonucleotide fingerprints of tryptophan tRNA purified in this manner are identical with those reported for \"spot 1\" RNA isolated from Rous sarcoma virus.", "contents": "Purification of tryptophan transfer RNA from chick cells and its identity with \"spot 1\" RNA of Rous sarcoma virus. Tryptophan transfer RNA from chick cells chromatographs differently in the reversed-phase column chromatographic system 5 depending upon whether it is aminoacylated or not. This property was utilized to prepare pure tryptophan tRNA. Oligonucleotide fingerprints of tryptophan tRNA purified in this manner are identical with those reported for \"spot 1\" RNA isolated from Rous sarcoma virus."} {"id": "PMID:169255", "title": "A study of the binding of Mn2+ to bovine pancreatic deoxyribonuclease I and to deoxyribonucleic acid by electron paramagnetic resonance.", "content": "EPR studies of Mn2+ binding to bovine pancreatic deoxyribonuclease I show that the enzyme can bind three Mn2+ ions at pH 7.5 and 2 degrees. Two sites bind Mn2+ strongly, with a Kd of 10(-4)M, and the third binds Mn2+ weakly, with a Kd of 10(-3)M. Ca2+ competes with the two strong sites, whereas Mg2+ competes only with one of them, indicating that both sites are not equivalent. Mn2+ binding to DNA has been confirmed by EPR measurements. Two types of sites, with different affinities for Mn2+ binding, were found on DNA molecules, one with a Kd of 1.2 times 10(-4)M and the other with a Kd of 10(-3)M. Mg2+ ions can displace Mn2+ from the high affinity sites, but not from the low affinity sites. These results suggest the Mn2+ binds not only to the phosphate groups, but also to the electron donor groups of the base rings.", "contents": "A study of the binding of Mn2+ to bovine pancreatic deoxyribonuclease I and to deoxyribonucleic acid by electron paramagnetic resonance. EPR studies of Mn2+ binding to bovine pancreatic deoxyribonuclease I show that the enzyme can bind three Mn2+ ions at pH 7.5 and 2 degrees. Two sites bind Mn2+ strongly, with a Kd of 10(-4)M, and the third binds Mn2+ weakly, with a Kd of 10(-3)M. Ca2+ competes with the two strong sites, whereas Mg2+ competes only with one of them, indicating that both sites are not equivalent. Mn2+ binding to DNA has been confirmed by EPR measurements. Two types of sites, with different affinities for Mn2+ binding, were found on DNA molecules, one with a Kd of 1.2 times 10(-4)M and the other with a Kd of 10(-3)M. Mg2+ ions can displace Mn2+ from the high affinity sites, but not from the low affinity sites. These results suggest the Mn2+ binds not only to the phosphate groups, but also to the electron donor groups of the base rings."} {"id": "PMID:169256", "title": "Interaction of L-alpha-palmitoyl lysophosphatidylcholine with the AI polypeptide of high density lipoprotein.", "content": "The AI polypeptide chain from human high density serum lipoprotein has two accessible conformational states in aqueous solution. L-alpha-Palmitoyl lysophosphatidylcholine induces the transition between these two states at an equilibrium concentration of ligand of 2 X 10(-5)M, and the protein has a maximum binding capacity of 95 to 100 mol of lipid/mol of protein. The present study, together with previous investigations in this laboratory, suggests that the conformational state of AI in the presence of high levels of bound amphiphiles is similar to the in vivo state, and further, that this complex does not result from the insertion of AI into amphiphilic micelles. The mode of interaction of AI with amphiphilic ligands is shown to be significantly different from that of membrane proteins thus far investigated.", "contents": "Interaction of L-alpha-palmitoyl lysophosphatidylcholine with the AI polypeptide of high density lipoprotein. The AI polypeptide chain from human high density serum lipoprotein has two accessible conformational states in aqueous solution. L-alpha-Palmitoyl lysophosphatidylcholine induces the transition between these two states at an equilibrium concentration of ligand of 2 X 10(-5)M, and the protein has a maximum binding capacity of 95 to 100 mol of lipid/mol of protein. The present study, together with previous investigations in this laboratory, suggests that the conformational state of AI in the presence of high levels of bound amphiphiles is similar to the in vivo state, and further, that this complex does not result from the insertion of AI into amphiphilic micelles. The mode of interaction of AI with amphiphilic ligands is shown to be significantly different from that of membrane proteins thus far investigated."} {"id": "PMID:169257", "title": "Pulmonary angiotensin-converting enzyme. Structural and catalytic properties.", "content": "Angiotensin-converting enzyme has been solubilized from a particulate fraction of rabbit lung and purified to apparent homogeneity in 11% yield by a procedure including fractionation with DEAE-cellulose and calcium phosphate gel, elution from Sephadex G-200, and lectin affinity chromatography. The molecular weight estimated by equilibrium sedimentation was approximately 129,000, either in the absence or presence of 6 M guanidine hydrochloride. A slightly higher value of 140,000 determined for the reduced, denatured protein by gel electrophoresis in the presence of sodium dodecyl sulfate and a much higher figure derived from gel filtration are probably due to the glycoprotein nature of the enzyme. Its oligosaccharide content accounted for 26% of the weight calculated from its amino acid and carbohydrate composition. The estimated content of sugar residues per mole was: galactose, 57; N-acetylglucosamine, 53; mannose, 43; N-acetylneuraminic acid, 19; and fucose, 4. Threonine and alanine were identified, respectively, as NH2-terminal and COOH-terminal residues by the dansylation procedure and by digestion with carboxypeptidase A. The enzyme was found to contain approximately 1 g atom of zinc per mol. Km values for hydrolysis of hippurylhistidylleucine and angiotensin I were 2.3 and 0.07 mM, and the corresponding turnover numbers were 15,430 and 792 mol/min/mol at 37 degrees. Bradykinin was also a substrate, and release of its COOH-terminal dipeptide, Phe-Arg, was catalyzed at a comparable rate to that of His-Leu from the COOH terminus of angiotensin I. Enzyme activity required the presence of chloride ions and was inhibited by EDTA and by low concentrations of Bothrops bradykinin-potentiating peptides. In addition, hydrolysis of hippurylhistidylleucine was inhibited competitively by other defined peptides, including di- and tripeptides, which were not substrates.", "contents": "Pulmonary angiotensin-converting enzyme. Structural and catalytic properties. Angiotensin-converting enzyme has been solubilized from a particulate fraction of rabbit lung and purified to apparent homogeneity in 11% yield by a procedure including fractionation with DEAE-cellulose and calcium phosphate gel, elution from Sephadex G-200, and lectin affinity chromatography. The molecular weight estimated by equilibrium sedimentation was approximately 129,000, either in the absence or presence of 6 M guanidine hydrochloride. A slightly higher value of 140,000 determined for the reduced, denatured protein by gel electrophoresis in the presence of sodium dodecyl sulfate and a much higher figure derived from gel filtration are probably due to the glycoprotein nature of the enzyme. Its oligosaccharide content accounted for 26% of the weight calculated from its amino acid and carbohydrate composition. The estimated content of sugar residues per mole was: galactose, 57; N-acetylglucosamine, 53; mannose, 43; N-acetylneuraminic acid, 19; and fucose, 4. Threonine and alanine were identified, respectively, as NH2-terminal and COOH-terminal residues by the dansylation procedure and by digestion with carboxypeptidase A. The enzyme was found to contain approximately 1 g atom of zinc per mol. Km values for hydrolysis of hippurylhistidylleucine and angiotensin I were 2.3 and 0.07 mM, and the corresponding turnover numbers were 15,430 and 792 mol/min/mol at 37 degrees. Bradykinin was also a substrate, and release of its COOH-terminal dipeptide, Phe-Arg, was catalyzed at a comparable rate to that of His-Leu from the COOH terminus of angiotensin I. Enzyme activity required the presence of chloride ions and was inhibited by EDTA and by low concentrations of Bothrops bradykinin-potentiating peptides. In addition, hydrolysis of hippurylhistidylleucine was inhibited competitively by other defined peptides, including di- and tripeptides, which were not substrates."} {"id": "PMID:169258", "title": "Isolation and characterization of cytidine diphosphate diglyceride from beef liver.", "content": "Cytidine diphosphate diglyceride was isolated from beef liver by a combination of silicic acid column, DEAE-cellulose column, and this layer chromatography. The product (5.8 to 17.4 mumol/kg of liver) contained cytidine/phosphate/fatty acids in the molar proportions 1.05/2.0/2.05 (theoretical, 1.0/2.0/2.0) (average for three preparations). The liponucleotide was split quantitatively by a partially purified hydrolase from Escherichia coli, specific for CDP-diglyceride, (Raetz, C. R. H., Hirschberg, C. B., Dowhan, W., Wickner, W. T., and Kennedy, E. P. (1972) J. Biol. Chem. 247, 2245-2247) into phosphatidic acid and a water-soluble nucleotide that was chromatographically identical with CMP. No dCMP was located in these hydrolysates. The liver liponucleotide was more effective than a synthetic preparation of CDP-diglyceride in promoting the formation of phosphatidylinositol with guinea pig brain microsomes. The fatty acid composition of CDP-diglyceride was compared with metabolically related phospholipids from beef liver. The liponucleotide had a similar composition to phosphatidylinositol, characterized by a high level of stearate and with arachidonate as the major unsaturated fatty acid. The content of arachidonate in both lipids was significantly higher than that in phosphatidic acid. The profile of fatty acids of cardiolipin was quite unlike that of CDP-diglyceride. These findings suggest several alternatives for the metabolic origins of beef liver CDP-diglyceride: (a) CDP-diglyceride is formed from an atypical pool of phosphatidic acid, (b) the enzyme is selective for arachidonoyl-containing species of phosphatidic acid, (c) the liponucleotide may also be derived from phosphatidylinositol by the back-reaction of CDP-diglyceride: inositol phosphatidyltransferase.", "contents": "Isolation and characterization of cytidine diphosphate diglyceride from beef liver. Cytidine diphosphate diglyceride was isolated from beef liver by a combination of silicic acid column, DEAE-cellulose column, and this layer chromatography. The product (5.8 to 17.4 mumol/kg of liver) contained cytidine/phosphate/fatty acids in the molar proportions 1.05/2.0/2.05 (theoretical, 1.0/2.0/2.0) (average for three preparations). The liponucleotide was split quantitatively by a partially purified hydrolase from Escherichia coli, specific for CDP-diglyceride, (Raetz, C. R. H., Hirschberg, C. B., Dowhan, W., Wickner, W. T., and Kennedy, E. P. (1972) J. Biol. Chem. 247, 2245-2247) into phosphatidic acid and a water-soluble nucleotide that was chromatographically identical with CMP. No dCMP was located in these hydrolysates. The liver liponucleotide was more effective than a synthetic preparation of CDP-diglyceride in promoting the formation of phosphatidylinositol with guinea pig brain microsomes. The fatty acid composition of CDP-diglyceride was compared with metabolically related phospholipids from beef liver. The liponucleotide had a similar composition to phosphatidylinositol, characterized by a high level of stearate and with arachidonate as the major unsaturated fatty acid. The content of arachidonate in both lipids was significantly higher than that in phosphatidic acid. The profile of fatty acids of cardiolipin was quite unlike that of CDP-diglyceride. These findings suggest several alternatives for the metabolic origins of beef liver CDP-diglyceride: (a) CDP-diglyceride is formed from an atypical pool of phosphatidic acid, (b) the enzyme is selective for arachidonoyl-containing species of phosphatidic acid, (c) the liponucleotide may also be derived from phosphatidylinositol by the back-reaction of CDP-diglyceride: inositol phosphatidyltransferase."} {"id": "PMID:169259", "title": "Human phosphoribosylpyrophosphate synthetase. Comparison of purified normal and mutant enzymes.", "content": "Human phosphoribosylpyrophosphate synthetase has been purified 4500-fold to electrophoretic homogeneity from the erythrocytes of normal individuals and of two brothers in whom excessive activity of this enzyme results in excessive rated of purine nucleotide and uric acid synthesis de novo and gouty arthritis. Structural differences between the normal and mutant enzymes are indicated by a lower isoelectric point for the mutant enzyme (pI 4.85) than for the normal enzyme (pI 5.10); decreased electrophoretic mobility of the mutant preparation on cellulose acetate gel at low inorganic phosphate concentrations; increased (2.4-fold) inactivation of the mutant enzyme activity relative to the normal by identical amounts of a specific antiserum which precipitates identical quantities of normal and mutant enzyme; increased thermal lability of the mutant enzyme at 55 degrees; and an increased (2.2-fold) specific enzyme activity for the mutant enzyme despite the comparable purity of the preparations. Antibody inactivation, quantitative precipitin, and immunodiffusion studies as well as the disparity in specific enzyme activities during the course of purification suggest that a structural alteration in the mutant enzyme leads to increased catalytic activity per enzyme molecule, either from a primary alteration in the structural gene(s) for phosphoribosylpyrophosphate synthetase or from a post-transcriptional alteration in the enzyme. Purified preparations of normal and mutant enzymes showed nearly identical affinity constants for magnesium and the substrates, ATP and ribose 5-phosphate, as well as similar inhibition constants for the products, PP-ribose-P and AMP, and the inhibitors ADP, GDP, and 2,3-diphosphoglycerate. An increased maximal velocity of the reaction was, thus, the sole kinetic difference identified. The increased velocity of the mutant enzyme reaction was constant over a range of inorganic phosphate concentrations from 0.1 to 100 mM. Subunit molecular weights of the enzyme preparations, estimated by sodium dodecyl sulfate-polyacrylamide electrophoresis, were identical (32,000), although the undenatured mutant enzyme showed a greater proportion of stainable protein in the smaller of two molecular weight forms (both greater than 500,000) of the enzyme demonstrated on polyacrylamide gel electrophoresis in the presence of 1 mM sodium phosphate.", "contents": "Human phosphoribosylpyrophosphate synthetase. Comparison of purified normal and mutant enzymes. Human phosphoribosylpyrophosphate synthetase has been purified 4500-fold to electrophoretic homogeneity from the erythrocytes of normal individuals and of two brothers in whom excessive activity of this enzyme results in excessive rated of purine nucleotide and uric acid synthesis de novo and gouty arthritis. Structural differences between the normal and mutant enzymes are indicated by a lower isoelectric point for the mutant enzyme (pI 4.85) than for the normal enzyme (pI 5.10); decreased electrophoretic mobility of the mutant preparation on cellulose acetate gel at low inorganic phosphate concentrations; increased (2.4-fold) inactivation of the mutant enzyme activity relative to the normal by identical amounts of a specific antiserum which precipitates identical quantities of normal and mutant enzyme; increased thermal lability of the mutant enzyme at 55 degrees; and an increased (2.2-fold) specific enzyme activity for the mutant enzyme despite the comparable purity of the preparations. Antibody inactivation, quantitative precipitin, and immunodiffusion studies as well as the disparity in specific enzyme activities during the course of purification suggest that a structural alteration in the mutant enzyme leads to increased catalytic activity per enzyme molecule, either from a primary alteration in the structural gene(s) for phosphoribosylpyrophosphate synthetase or from a post-transcriptional alteration in the enzyme. Purified preparations of normal and mutant enzymes showed nearly identical affinity constants for magnesium and the substrates, ATP and ribose 5-phosphate, as well as similar inhibition constants for the products, PP-ribose-P and AMP, and the inhibitors ADP, GDP, and 2,3-diphosphoglycerate. An increased maximal velocity of the reaction was, thus, the sole kinetic difference identified. The increased velocity of the mutant enzyme reaction was constant over a range of inorganic phosphate concentrations from 0.1 to 100 mM. Subunit molecular weights of the enzyme preparations, estimated by sodium dodecyl sulfate-polyacrylamide electrophoresis, were identical (32,000), although the undenatured mutant enzyme showed a greater proportion of stainable protein in the smaller of two molecular weight forms (both greater than 500,000) of the enzyme demonstrated on polyacrylamide gel electrophoresis in the presence of 1 mM sodium phosphate."} {"id": "PMID:169260", "title": "Reversibility of adenosine 3':5'-monophosphate-dependent protein kinase reactions.", "content": "Using a homogeneous enzyme from rabbit skeletal muscle, it has been demonstrated that the cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase reaction is reversible. In addition to the phosphorylated protein substrate, the reverse reaction requires Mg2+, ADP, and cyclic AMP when the holoenzyme is used as the source of enzyme. It is independent of cyclic AMP when the catalytic subunit of the protein kinase is used. The optimum pH for the reverse reaction with 32P-labeled casein as the substrate is 5.7, essentially the same as that for the forward reaction. Among the nucleotide subtrates tested, ADP serves as the best phosphoryl group acceptor. The Km of the enzyme for ADP is 3.3 mM and that for 32P-casein is 1.7 mg/ml. The equilibrium constant at 30 degrees is approximately 0.042 at a magnesium concentration of 10 mM and a pH of 6.9. This result indicates that the free energy of hydrolysis (deltaG0obs) of the phosphorylated protein substrate is relatively high, i.e. approximately -6.5 kcal/mol under these conditions.", "contents": "Reversibility of adenosine 3':5'-monophosphate-dependent protein kinase reactions. Using a homogeneous enzyme from rabbit skeletal muscle, it has been demonstrated that the cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase reaction is reversible. In addition to the phosphorylated protein substrate, the reverse reaction requires Mg2+, ADP, and cyclic AMP when the holoenzyme is used as the source of enzyme. It is independent of cyclic AMP when the catalytic subunit of the protein kinase is used. The optimum pH for the reverse reaction with 32P-labeled casein as the substrate is 5.7, essentially the same as that for the forward reaction. Among the nucleotide subtrates tested, ADP serves as the best phosphoryl group acceptor. The Km of the enzyme for ADP is 3.3 mM and that for 32P-casein is 1.7 mg/ml. The equilibrium constant at 30 degrees is approximately 0.042 at a magnesium concentration of 10 mM and a pH of 6.9. This result indicates that the free energy of hydrolysis (deltaG0obs) of the phosphorylated protein substrate is relatively high, i.e. approximately -6.5 kcal/mol under these conditions."} {"id": "PMID:169261", "title": "Interaction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction.", "content": "The denatured alpha1(I) chain and the cyanogen bromide peptide, alpha1(I)-CB5, of chick skin collagen cause the release of serotonin and leakage of lactic dehydrogenase from human platelets in a manner similar to the release reaction mediated by adenosine diphosphate and native collagen. These peptides also cause a decrease in the level of adenosine 3':5'-monophosphate (cAMP) in platelets. Adenylate cyclase activity of platelets is partially inhibited by these peptides as well as by native collagen, ADP, and epinephrine, but cAMP phosphodiesterase activity is unaltered by these substances. In contrast, the level of platelet guanosine 3':5'-monophosphate (cGMP) is increased by the collagen peptides as well as the other aggregating agents. The increase is associated with increased guanylate cyclase, but normal cGMP phosphodiesterase activities of platelets. Optical rotatory and viscometric measurements of the alpha1 chains and alpha1-CB5 of chick skin in 0.01 M phosphate/0.15 M sodium chloride, pH 7.4, at various temperatures as a function of time indicate that no detectable renaturation occurs at 37 degrees for at least 30 min of observation. Molecular sieve chromatography of alpha1-CB5 in the phosphate buffer at 37 degrees shows that its elution position is identical to that performed under denaturing conditions (at 45 degrees) with no evidence of higher molecular weight aggregates, and the alpha1-CB5 glycopeptide fraction eluting from the column at the position of its monomer retains the platelet aggregating activity. Additionally, electron microscopic examination of the platelet-rich plasma that had been reacted with these peptides fail to show any ordered collagen structures. These data indicate that the denatured alpha1 chain and alpha1-CB5 glycopeptide of chick skin collagen mediate platelet aggregation through the \"physiologic\" release reaction in a manner similar to that induced by other aggregating agents such as ADP, epinephrine, or native collagen, and support the conclusion that the aggregating activity of the alpha1 chain and alpha1-CB5 is not likely to be due to the formation of polymerized products.", "contents": "Interaction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction. The denatured alpha1(I) chain and the cyanogen bromide peptide, alpha1(I)-CB5, of chick skin collagen cause the release of serotonin and leakage of lactic dehydrogenase from human platelets in a manner similar to the release reaction mediated by adenosine diphosphate and native collagen. These peptides also cause a decrease in the level of adenosine 3':5'-monophosphate (cAMP) in platelets. Adenylate cyclase activity of platelets is partially inhibited by these peptides as well as by native collagen, ADP, and epinephrine, but cAMP phosphodiesterase activity is unaltered by these substances. In contrast, the level of platelet guanosine 3':5'-monophosphate (cGMP) is increased by the collagen peptides as well as the other aggregating agents. The increase is associated with increased guanylate cyclase, but normal cGMP phosphodiesterase activities of platelets. Optical rotatory and viscometric measurements of the alpha1 chains and alpha1-CB5 of chick skin in 0.01 M phosphate/0.15 M sodium chloride, pH 7.4, at various temperatures as a function of time indicate that no detectable renaturation occurs at 37 degrees for at least 30 min of observation. Molecular sieve chromatography of alpha1-CB5 in the phosphate buffer at 37 degrees shows that its elution position is identical to that performed under denaturing conditions (at 45 degrees) with no evidence of higher molecular weight aggregates, and the alpha1-CB5 glycopeptide fraction eluting from the column at the position of its monomer retains the platelet aggregating activity. Additionally, electron microscopic examination of the platelet-rich plasma that had been reacted with these peptides fail to show any ordered collagen structures. These data indicate that the denatured alpha1 chain and alpha1-CB5 glycopeptide of chick skin collagen mediate platelet aggregation through the \"physiologic\" release reaction in a manner similar to that induced by other aggregating agents such as ADP, epinephrine, or native collagen, and support the conclusion that the aggregating activity of the alpha1 chain and alpha1-CB5 is not likely to be due to the formation of polymerized products."} {"id": "PMID:169262", "title": "The carboxylic acid groups of bovine luteinizing hormone. The effects of their modification on receptor site binding and subunit-subunit interaction.", "content": "The modification of the carboxyl groups of the subunits of bovine luteinizing hormone to neutral derivatives by carbodiimide-mediated coupling with glycine methyl ester has been studied. The modified alpha subunit, which has 8 residues of glycine methyl ester incorporated, will no longer recombine with native beta (hormone-specific) subunit, but the modified beta subunit, with 6 to 7 glycine methyl esters incorporated, will recombine with native alpha to yield a partially active hormone. Derivatization of the intact hormone results in dissociation to subunits together with formation of a major side product which is covalently cross-linked. Significant cross-linked product was not obtained during modification of individual subunits, thus indicating an orientation between an activated carboxyl group(s) and a nucleophile(s) in the intact hormone which favors coupling. Separation of subunits from the derivatized, noncross-linked fraction by countercurrent distribution reveals a heterogeneous preparation of the modified alpha subunit which also will not recombine with either a native or modified beta subunit. The beta subunit from the modified intact hormone was indistinguishable from the modified isolated beta subunit in amino acid composition and in ability to recombine with native alpha subunit. The results are consonant with data from this and other laboratories in which various modifications of the alpha chain, the subunit common to the glycoproteins, more seriously affect recombination than similar modifications of the beta subunits. The number of carboxyl groups modified in each subunit is compatible with but not in total agreement with assignments of amides reported from sequence studies.", "contents": "The carboxylic acid groups of bovine luteinizing hormone. The effects of their modification on receptor site binding and subunit-subunit interaction. The modification of the carboxyl groups of the subunits of bovine luteinizing hormone to neutral derivatives by carbodiimide-mediated coupling with glycine methyl ester has been studied. The modified alpha subunit, which has 8 residues of glycine methyl ester incorporated, will no longer recombine with native beta (hormone-specific) subunit, but the modified beta subunit, with 6 to 7 glycine methyl esters incorporated, will recombine with native alpha to yield a partially active hormone. Derivatization of the intact hormone results in dissociation to subunits together with formation of a major side product which is covalently cross-linked. Significant cross-linked product was not obtained during modification of individual subunits, thus indicating an orientation between an activated carboxyl group(s) and a nucleophile(s) in the intact hormone which favors coupling. Separation of subunits from the derivatized, noncross-linked fraction by countercurrent distribution reveals a heterogeneous preparation of the modified alpha subunit which also will not recombine with either a native or modified beta subunit. The beta subunit from the modified intact hormone was indistinguishable from the modified isolated beta subunit in amino acid composition and in ability to recombine with native alpha subunit. The results are consonant with data from this and other laboratories in which various modifications of the alpha chain, the subunit common to the glycoproteins, more seriously affect recombination than similar modifications of the beta subunits. The number of carboxyl groups modified in each subunit is compatible with but not in total agreement with assignments of amides reported from sequence studies."} {"id": "PMID:169263", "title": "Site of synthesis of membrane and nonmembrane proteins of vesicular stomatitis virus.", "content": "Upon infection of Chinese hamster ovary cells (CHO), vesicular stomatitis (VSV) virus synthesizes two membrane proteins (the VSV glycoprotein and the VSV matrix or membrane (M) protein) and three nonmembrane proteins (the VSV nucleocapsid, the viral transcriptase, and an NS protein). We have used the VSV-infected cell as a model system for the study of the site of synthesis of these membrane and nonmembrane proteins. We have isolated VSV mRNA from free polyribosomes, membrane-bound polyribosomes, and the postribosomal supernatant, and identified the individual species of VSV mRNA present in each fraction. The mRNA which encodes the VSV glycoprotein is found exclusively on membrane-bound polyribosomes, while the mRNAs which encode the VSV, M, N, and NS proteins are found in free polyribosomes, in the membrane fraction of the cell, and in the postribosomal supernatant. Our results suggest that the VSV glycoprotein is synthesized exclusively on membrane polyribosomes, while at least some of the M, N, and NS proteins are made on free polyribosomes.", "contents": "Site of synthesis of membrane and nonmembrane proteins of vesicular stomatitis virus. Upon infection of Chinese hamster ovary cells (CHO), vesicular stomatitis (VSV) virus synthesizes two membrane proteins (the VSV glycoprotein and the VSV matrix or membrane (M) protein) and three nonmembrane proteins (the VSV nucleocapsid, the viral transcriptase, and an NS protein). We have used the VSV-infected cell as a model system for the study of the site of synthesis of these membrane and nonmembrane proteins. We have isolated VSV mRNA from free polyribosomes, membrane-bound polyribosomes, and the postribosomal supernatant, and identified the individual species of VSV mRNA present in each fraction. The mRNA which encodes the VSV glycoprotein is found exclusively on membrane-bound polyribosomes, while the mRNAs which encode the VSV, M, N, and NS proteins are found in free polyribosomes, in the membrane fraction of the cell, and in the postribosomal supernatant. Our results suggest that the VSV glycoprotein is synthesized exclusively on membrane polyribosomes, while at least some of the M, N, and NS proteins are made on free polyribosomes."} {"id": "PMID:169264", "title": "Multiple thermotropic phase transitions in Escherichia coli membranes and membrane lipids. A comparison of results obtained by nitroxyl stearate paramagnetic resonance, pyrene excimer fluorescence, and enzyme activity measurements.", "content": "At characteristic temperatures, membranes from Escherichia coli cells enriched in exogenous elaidic acid exhibit two abrupt changes in the slope of Arrhenius plots of two enzyme activities. For NADH oxidase, these changes occur at 27 degrees and 32 degrees, whereas for D-lactate oxidase, these changes occur at 31 degrees and 36 degrees. Pyrene excimer fluorescence and spin-labeled fatty acid paramagnetic resonance results indicate that the beginning, midpoint, and end of a single structural change(order leads to disorder transition) occurs at 25.5-29.0 degrees, 30.0-31.0 degrees, and 33.0-35.5 degrees, respectively. These data suggest that for NADH oxidase, the observed activity changes correspond to the beginning and midpoint of a single membrane lipid structural change, whereas for D-lactate, the activity changes correspond to the midpoint and end of that structural change. In addition to the membrane structural change spanning the range of 25.5-35.5 degrees, a second change (9.5-21.0 degrees) was also observed. This transition was detected by 5- and 16-2,2-dimethyloxazolidinyl-1-oxyl (doxyl) stearates, but not by 12-doxyl stearate or pyrene. Structural changes in the extracted lipids were observed in the temperature ranges 4.0-9.0 degrees, 14.0-20.0 degrees, and 25.0-35.5 degrees. The two higher ranges correlate well with the ranges for structural changes observed in the intact membrane. Observations of these multiple transitions in both intact membranes and extracted lipids strongly suggest that these lipids segregate into domains of different fluidity and composition.", "contents": "Multiple thermotropic phase transitions in Escherichia coli membranes and membrane lipids. A comparison of results obtained by nitroxyl stearate paramagnetic resonance, pyrene excimer fluorescence, and enzyme activity measurements. At characteristic temperatures, membranes from Escherichia coli cells enriched in exogenous elaidic acid exhibit two abrupt changes in the slope of Arrhenius plots of two enzyme activities. For NADH oxidase, these changes occur at 27 degrees and 32 degrees, whereas for D-lactate oxidase, these changes occur at 31 degrees and 36 degrees. Pyrene excimer fluorescence and spin-labeled fatty acid paramagnetic resonance results indicate that the beginning, midpoint, and end of a single structural change(order leads to disorder transition) occurs at 25.5-29.0 degrees, 30.0-31.0 degrees, and 33.0-35.5 degrees, respectively. These data suggest that for NADH oxidase, the observed activity changes correspond to the beginning and midpoint of a single membrane lipid structural change, whereas for D-lactate, the activity changes correspond to the midpoint and end of that structural change. In addition to the membrane structural change spanning the range of 25.5-35.5 degrees, a second change (9.5-21.0 degrees) was also observed. This transition was detected by 5- and 16-2,2-dimethyloxazolidinyl-1-oxyl (doxyl) stearates, but not by 12-doxyl stearate or pyrene. Structural changes in the extracted lipids were observed in the temperature ranges 4.0-9.0 degrees, 14.0-20.0 degrees, and 25.0-35.5 degrees. The two higher ranges correlate well with the ranges for structural changes observed in the intact membrane. Observations of these multiple transitions in both intact membranes and extracted lipids strongly suggest that these lipids segregate into domains of different fluidity and composition."} {"id": "PMID:169265", "title": "Coordinate regulation of adenylate cyclase and carbohydrate permeases by the phosphoenolpyruvate:sugar phosphotransferase system in Salmonella typhimurium.", "content": "Adenylate cyclase (EC 4.6.1.1) and several carbohydrate permeases are inhibited by D-glucose and other substrates of the phosphoenolpyruvate:sugar phosphotransferase system. These activities are coordinately altered by sugar substrates of the phosphotransferase system in a variety of bacterial strains which contain differing cellular levels of the protein components of the phosphotransferase system: Enzyme I, a small heat-stable protein, and Enzyme II. It is suggested that the activities of adenylate cyclase and the permease proteins are subject to allosteric regulation and that the allosteric effector is a regulatory protein which can be phosphorylated by the phosphotransferase system.", "contents": "Coordinate regulation of adenylate cyclase and carbohydrate permeases by the phosphoenolpyruvate:sugar phosphotransferase system in Salmonella typhimurium. Adenylate cyclase (EC 4.6.1.1) and several carbohydrate permeases are inhibited by D-glucose and other substrates of the phosphoenolpyruvate:sugar phosphotransferase system. These activities are coordinately altered by sugar substrates of the phosphotransferase system in a variety of bacterial strains which contain differing cellular levels of the protein components of the phosphotransferase system: Enzyme I, a small heat-stable protein, and Enzyme II. It is suggested that the activities of adenylate cyclase and the permease proteins are subject to allosteric regulation and that the allosteric effector is a regulatory protein which can be phosphorylated by the phosphotransferase system."} {"id": "PMID:169267", "title": "Arthritic disorders of the adult radiocarpal joint: anatomic considerations and an evaluation of fifty consecutive abnormal cases.", "content": "The anatomy and pathology of the radiocarpal compartment of the adult wrist are described in a study of human cadavers and 50 consecutive patients with radiocarpal joint abnormalities. The most frequently encountered diseases were adult onset rheumatoid arthritis (42) and calcium pyrophosphate deposition disease (22%). Features allowing radiographic diagnosis included the degree of symmetry and the presence of demineralization, sclerosis, joint space narrowing, subchondral cysts and erosions. Evaluation of abnormalities in other compartments of the wrist and the ulnar styloid is mandatory.", "contents": "Arthritic disorders of the adult radiocarpal joint: anatomic considerations and an evaluation of fifty consecutive abnormal cases. The anatomy and pathology of the radiocarpal compartment of the adult wrist are described in a study of human cadavers and 50 consecutive patients with radiocarpal joint abnormalities. The most frequently encountered diseases were adult onset rheumatoid arthritis (42) and calcium pyrophosphate deposition disease (22%). Features allowing radiographic diagnosis included the degree of symmetry and the presence of demineralization, sclerosis, joint space narrowing, subchondral cysts and erosions. Evaluation of abnormalities in other compartments of the wrist and the ulnar styloid is mandatory."} {"id": "PMID:169268", "title": "[A functional flagella with a 6 + 0 pattern].", "content": "The male gamete of the Gregarine Lecudina tuzetae has been studied with transmission electron microscopy and microcinematography. It is characterized by a flagellar axoneme of 6 + 0 pattern, a reduction of the chondriome, and the abundance of storage polysaccharide or lipid bodies. The movements of the flagella are of the undulating type and they are performed in the three dimensions of space. They are very slow, with a cycle time of about 2s. The structure of the axoneme components are similar to those of flagella with a 9 + 2 pattern. Each doublet has overall dimensions of 350 x 220 A; the space between the adjacent doublets is about 160 A. The A subfiber bears arms like dynein arms. The diameter of the axoneme is about 1,000 A. The basal body consists of a cylinder of dense material 2,500 A long and 1,300-1,400 A in diameter; a microtubule 200 A in diameter is present in the axis. This study shows that a 6 + 0 pattern can generate a flagellar movement. The mechanism of the flagellar movement of the male gamete of L. tuzetae does not require the presence of central microtubules and it would include molecular interactions of the dynein-tubulin type between the adjacent peripheric doublets. The slowness of the movements is discussed in terms of the axoneme's structure and its energy supply. Finally, the phylogenetic significance of this flagella is examined on the basis of the morphopoietic potentialities of the centriolar structures.", "contents": "[A functional flagella with a 6 + 0 pattern]. The male gamete of the Gregarine Lecudina tuzetae has been studied with transmission electron microscopy and microcinematography. It is characterized by a flagellar axoneme of 6 + 0 pattern, a reduction of the chondriome, and the abundance of storage polysaccharide or lipid bodies. The movements of the flagella are of the undulating type and they are performed in the three dimensions of space. They are very slow, with a cycle time of about 2s. The structure of the axoneme components are similar to those of flagella with a 9 + 2 pattern. Each doublet has overall dimensions of 350 x 220 A; the space between the adjacent doublets is about 160 A. The A subfiber bears arms like dynein arms. The diameter of the axoneme is about 1,000 A. The basal body consists of a cylinder of dense material 2,500 A long and 1,300-1,400 A in diameter; a microtubule 200 A in diameter is present in the axis. This study shows that a 6 + 0 pattern can generate a flagellar movement. The mechanism of the flagellar movement of the male gamete of L. tuzetae does not require the presence of central microtubules and it would include molecular interactions of the dynein-tubulin type between the adjacent peripheric doublets. The slowness of the movements is discussed in terms of the axoneme's structure and its energy supply. Finally, the phylogenetic significance of this flagella is examined on the basis of the morphopoietic potentialities of the centriolar structures."} {"id": "PMID:169269", "title": "The permeability of muscle capillaries to horseradish peroxidase.", "content": "The main objective of this study was to determine the pathways by which horseradish peroxidase (HRP) can cross the endothelium of muscle capillaries. Specimens of mouse diaphragm were fixed for cytochemical analysis at various intervals after intervenous injection of 0.5 mg HRP, at 4 min after intervenous injection of varied amounts of HRP, and at 4 min after intervenous injections in various volumes of isotonic NaCl. Our findings indicate that endothelial junctions serve as a barrier which may allow passage of very limited amounts of HRP. They also suggest that endothelial vesicles transfer HRP from the capillary lumen to the pericapillary interstitium as well as in the reverse direction. Increasing the volume of solution injected to approximately 30% of total blood volume did not increase the amount of HRP that left the capillary lumen. Our results with HRP do not provide clearcut evidence that endothelial junctions are the site of the small pore.", "contents": "The permeability of muscle capillaries to horseradish peroxidase. The main objective of this study was to determine the pathways by which horseradish peroxidase (HRP) can cross the endothelium of muscle capillaries. Specimens of mouse diaphragm were fixed for cytochemical analysis at various intervals after intervenous injection of 0.5 mg HRP, at 4 min after intervenous injection of varied amounts of HRP, and at 4 min after intervenous injections in various volumes of isotonic NaCl. Our findings indicate that endothelial junctions serve as a barrier which may allow passage of very limited amounts of HRP. They also suggest that endothelial vesicles transfer HRP from the capillary lumen to the pericapillary interstitium as well as in the reverse direction. Increasing the volume of solution injected to approximately 30% of total blood volume did not increase the amount of HRP that left the capillary lumen. Our results with HRP do not provide clearcut evidence that endothelial junctions are the site of the small pore."} {"id": "PMID:169270", "title": "Characterization of an SV40-transformed 3T3 cell line expressing an unusual phenotype.", "content": "A transformed variant derived as a clone from normal 3T3 cells infected with simian virus 40 (SV40) has been found to possess a phenotype intermediate between that of normal cells and that characteristic of the transformed state, yet cells of the variant still test positively for the SV40-specific nuclear T-antigen. The variant exercises growth control, although not as stringently as do normal cells. Its cell size more closely resembles that of normal cells than of transformed cells. The variant also exhibits levels of spontaneous agglutination that are in line with those characteristic of the normal cells from which it was derived, and far higher than corresponding values for cells exhibiting the fully transformed phenotype. Plasma membranes of variant cells more closely resemble those of transformed cells than of normal cells as estimated by polyacrylamide gel electrophoresis. Perhaps the most distinguishing characteristic of the transformed variant is its complete immunity to agglutination by concanavalin A (Con A), even at concentrations of the lectin as high as 500 mug/ml. Moreover, trypsinization does not render variant cells as agglutinable in the presence of Con A as are untreated fully transformed cells. By contrast the variant displays a low tolerance of Con A toxicity, as monitored by ability to grow after treatment with the lectin, and on this count resembles transformed cells. Moreover a survey of several normal cell lines has revealed that even they do not consistently show resistance to Con A toxicity. These observations indicate that Con A-mediated agglutination and inability to grow after treatment with Con A are quite independent and do not bear a cause and effect relationship.", "contents": "Characterization of an SV40-transformed 3T3 cell line expressing an unusual phenotype. A transformed variant derived as a clone from normal 3T3 cells infected with simian virus 40 (SV40) has been found to possess a phenotype intermediate between that of normal cells and that characteristic of the transformed state, yet cells of the variant still test positively for the SV40-specific nuclear T-antigen. The variant exercises growth control, although not as stringently as do normal cells. Its cell size more closely resembles that of normal cells than of transformed cells. The variant also exhibits levels of spontaneous agglutination that are in line with those characteristic of the normal cells from which it was derived, and far higher than corresponding values for cells exhibiting the fully transformed phenotype. Plasma membranes of variant cells more closely resemble those of transformed cells than of normal cells as estimated by polyacrylamide gel electrophoresis. Perhaps the most distinguishing characteristic of the transformed variant is its complete immunity to agglutination by concanavalin A (Con A), even at concentrations of the lectin as high as 500 mug/ml. Moreover, trypsinization does not render variant cells as agglutinable in the presence of Con A as are untreated fully transformed cells. By contrast the variant displays a low tolerance of Con A toxicity, as monitored by ability to grow after treatment with the lectin, and on this count resembles transformed cells. Moreover a survey of several normal cell lines has revealed that even they do not consistently show resistance to Con A toxicity. These observations indicate that Con A-mediated agglutination and inability to grow after treatment with Con A are quite independent and do not bear a cause and effect relationship."} {"id": "PMID:169271", "title": "The growth of the pollen tube wall in Oenothera organensis.", "content": "The growth of the pollen tube wall of Oenothera is effected by the expulsion of fibrillar material from the cytoplasm into the developing wall. This material may also be seen in the cytoplasm, contained in membrane-bound vesicles. It is not clear how the content of the vesicles is discharged, but it appears not to involve the participation of microtubules. The source of the cytoplasmic fibrillar bodies depends upon the stage of development of the pollen tube. The earilest growth is derived from the inclusion into the wall of vesicles containing pre-formed materials present in the grain on pollination. During the next stage of growth the wall is derived from the content of double-membraned inclusions also present in the pollen. The content of the former vesicles is not so similar to the wall as the latter, but intermediates between the 2 types of vesicle may be seen in the cytoplasm, indicating that the former are formed from the latter. Most of the tube wall is derived from the products of dictyosomes in the pollen grain or tube. These dicytosomes are few in number and they must be exceedingly active. This, and the observation that dictyosome vesicles are frequently associated with banked complexes of mitochondria, indicates that some steps in the metabolism of the vesicular content, perhaps phosphorylation, take place distant from the dicytosomes. These different sources of fibrillar material presumably permit the rapid starting of tube growth, without any attendant metabolism. However, it would be impossible to include enough pre-formed wall material in the grain to enable the full growth of the tube, so once started, it seems that the tube then relies on the elaboration of simple reserves for the contruction of its wall. These reserves are likely to be held in the pollen, and may be the large numbers of starch grains characteristic of the pollen cytoplasm.", "contents": "The growth of the pollen tube wall in Oenothera organensis. The growth of the pollen tube wall of Oenothera is effected by the expulsion of fibrillar material from the cytoplasm into the developing wall. This material may also be seen in the cytoplasm, contained in membrane-bound vesicles. It is not clear how the content of the vesicles is discharged, but it appears not to involve the participation of microtubules. The source of the cytoplasmic fibrillar bodies depends upon the stage of development of the pollen tube. The earilest growth is derived from the inclusion into the wall of vesicles containing pre-formed materials present in the grain on pollination. During the next stage of growth the wall is derived from the content of double-membraned inclusions also present in the pollen. The content of the former vesicles is not so similar to the wall as the latter, but intermediates between the 2 types of vesicle may be seen in the cytoplasm, indicating that the former are formed from the latter. Most of the tube wall is derived from the products of dictyosomes in the pollen grain or tube. These dicytosomes are few in number and they must be exceedingly active. This, and the observation that dictyosome vesicles are frequently associated with banked complexes of mitochondria, indicates that some steps in the metabolism of the vesicular content, perhaps phosphorylation, take place distant from the dicytosomes. These different sources of fibrillar material presumably permit the rapid starting of tube growth, without any attendant metabolism. However, it would be impossible to include enough pre-formed wall material in the grain to enable the full growth of the tube, so once started, it seems that the tube then relies on the elaboration of simple reserves for the contruction of its wall. These reserves are likely to be held in the pollen, and may be the large numbers of starch grains characteristic of the pollen cytoplasm."} {"id": "PMID:169276", "title": "High speed liquid-solid chromatography of phenothiazines using columns packed with spherosil porous silica beads.", "content": "Spherosil, a spherical porous silica, has been investigated for use in high speed liquid-solid chromatography and compared to Lichrosorb Si-60, using three phenothiazines as test solutes. Particle size distribution for four different size ranges with nominal mean diameters of 5, 10, 20 and 40 mu m is given. Distribution is very homogeneous. Columns from 15 to 100 cm in length and 1/4 or 1/8 in.o.d. have been prepared and efficiency measured by determination of HETP with the three phenothiazines: [methylamino-3-propyl]-10-chloro-3-phenothiazine [k' = 3]; [N-methyl-N-[dimethylamino-3-propyl]amino-3-propyl]-10-chloro-3-phenothiazine [k' = 6.5]; and [dimethylamino-3-propyl]-10-chloro-3-phenothiazine-N-oxide [k' = 15]. Influence of column length and incidence of bead diameter have been studied. 1/4 in.o.d. columns are easier to fill than 1/8 in.o.d. columns for Spherosil 5 mu m and have, therefore, a greater efficiency. HETP, H, varies according to flow rate as H = DVn with 0.4 less than n less than 0.6 and according to particle size ad H = A d beta p with 1.7 less than beta less than 1.8. The best figures for H are between 0.1 or 0.2 mm for a flow rate of 1800 ml hr-1 cm-2 [k' = 15]. The separation of a mixture of 6 phenothiazines with the mobile phase, anhydrous ethyl acetate 60 V, water saturated ethyl acetate 20 V, anhydrous methanol 20 V, 33% aqueous solution of ethylamine 0.25 V, is given. Its duration is 20 min. instead of 90 min. by thin-layer chromatography.", "contents": "High speed liquid-solid chromatography of phenothiazines using columns packed with spherosil porous silica beads. Spherosil, a spherical porous silica, has been investigated for use in high speed liquid-solid chromatography and compared to Lichrosorb Si-60, using three phenothiazines as test solutes. Particle size distribution for four different size ranges with nominal mean diameters of 5, 10, 20 and 40 mu m is given. Distribution is very homogeneous. Columns from 15 to 100 cm in length and 1/4 or 1/8 in.o.d. have been prepared and efficiency measured by determination of HETP with the three phenothiazines: [methylamino-3-propyl]-10-chloro-3-phenothiazine [k' = 3]; [N-methyl-N-[dimethylamino-3-propyl]amino-3-propyl]-10-chloro-3-phenothiazine [k' = 6.5]; and [dimethylamino-3-propyl]-10-chloro-3-phenothiazine-N-oxide [k' = 15]. Influence of column length and incidence of bead diameter have been studied. 1/4 in.o.d. columns are easier to fill than 1/8 in.o.d. columns for Spherosil 5 mu m and have, therefore, a greater efficiency. HETP, H, varies according to flow rate as H = DVn with 0.4 less than n less than 0.6 and according to particle size ad H = A d beta p with 1.7 less than beta less than 1.8. The best figures for H are between 0.1 or 0.2 mm for a flow rate of 1800 ml hr-1 cm-2 [k' = 15]. The separation of a mixture of 6 phenothiazines with the mobile phase, anhydrous ethyl acetate 60 V, water saturated ethyl acetate 20 V, anhydrous methanol 20 V, 33% aqueous solution of ethylamine 0.25 V, is given. Its duration is 20 min. instead of 90 min. by thin-layer chromatography."} {"id": "PMID:169278", "title": "Urinary and plasma cyclic adenosine 3',5'-monophosphate in patients with idiopathic edema.", "content": "Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone.", "contents": "Urinary and plasma cyclic adenosine 3',5'-monophosphate in patients with idiopathic edema. Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone."} {"id": "PMID:169279", "title": "A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man.", "content": "An assay for plasma glucocorticoid activity has been developed using specific glucocorticoid receptors. Unlike other assays for cortisol and certain synthetic corticosteroids, this radioreceptor assay measures the glucocorticoid activity of all natural an synthetic steroids. Steroids extracted from as little as 0.05 ml of plasma are incubated with 3H-dexamethasone and cytosol receptors from cultured rat hepatome cells. From 0.5 to 50 ng of cortisol are accurately detected. Glucocorticoid activities of adult determined by the assay correlate closely with corticoid levels obtained in the CBG-isotope and fluorometric assays. Other steroids are measured in proportion to both concentration and potency as glucocorticoids. Relative activities include: cortisol 100, dexamethasone 940, prednisolone 230, prednisone 3, estradiol 1 and androstenedione 1. A similar ranking of steroids was found using receptors from a human source (fetal lung). The assay has been useful in detecting glucocorticoid activity in unidentified medications and in measuring plasma glucocorticoid levels after administration of synthetic corticosteroids. A modification of the assay is described for also estimating the level of free (unbound) glucocorticoid activity in plasma. Assays are performed before and after removal by charcoal of steroids not bound to plasma transcortin. This consideration is shown to be particularly important with prednisolone where the unbound steroid level is much less than the total. Thus, the radioreceptor assay provides a relatively simple technique for measuring the total of free plasma of glucocorticoid activity in man due to any natural or synthetic steroid or combination of steroids.", "contents": "A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man. An assay for plasma glucocorticoid activity has been developed using specific glucocorticoid receptors. Unlike other assays for cortisol and certain synthetic corticosteroids, this radioreceptor assay measures the glucocorticoid activity of all natural an synthetic steroids. Steroids extracted from as little as 0.05 ml of plasma are incubated with 3H-dexamethasone and cytosol receptors from cultured rat hepatome cells. From 0.5 to 50 ng of cortisol are accurately detected. Glucocorticoid activities of adult determined by the assay correlate closely with corticoid levels obtained in the CBG-isotope and fluorometric assays. Other steroids are measured in proportion to both concentration and potency as glucocorticoids. Relative activities include: cortisol 100, dexamethasone 940, prednisolone 230, prednisone 3, estradiol 1 and androstenedione 1. A similar ranking of steroids was found using receptors from a human source (fetal lung). The assay has been useful in detecting glucocorticoid activity in unidentified medications and in measuring plasma glucocorticoid levels after administration of synthetic corticosteroids. A modification of the assay is described for also estimating the level of free (unbound) glucocorticoid activity in plasma. Assays are performed before and after removal by charcoal of steroids not bound to plasma transcortin. This consideration is shown to be particularly important with prednisolone where the unbound steroid level is much less than the total. Thus, the radioreceptor assay provides a relatively simple technique for measuring the total of free plasma of glucocorticoid activity in man due to any natural or synthetic steroid or combination of steroids."} {"id": "PMID:169280", "title": "Skeletal resistance to endogenous parathyroid hormone in pateints with early renal failure. A possible cause for secondary hyperparathyroidism.", "content": "Studies were carried out to evaluate whether skeletal resistance to acute increments in endogenous parathyroid hormone exists in patients with mild to moderate renal insufficiency. Hypocalcemia was induced with the infusion of ethyl-enediamine-tetra-acetate (EDTA) in 10 normal subjects and 13 patients with mild renal failure. After the induction of hypocalcemia, the concentration of serum calcium increased gradually and reached preinfusion levels by 22 h in the normal subjects; in contrast, the levels of serum calcium in patients with mild renal insufficiency were significantly lower than the preinfusion values even at the end of 26 h following the EDTA infusion. This delayed recovery occurred despite significantly higher levels of serum immunoreactive parathyroid hormone (IPTH) in the patients than in the normal subjects. The increase in the levels of IPTH reflect elevations in the concentrations of biologically active hormone since urinary cyclic AMP increased significantly. Urinary calcium excretion following the EDTA infusion was not different in both groups and, therefore, could not account for the delayed recovery of serum calcium values in the patients with renal insufficiency. These results indicate that secondary hyperparathyroidism exists early in patients with renal failure and such patients have exaggerated parathyroid hormone secretion in response to acute hypocalcemia. The data are consistent with the concept that skeletal resistance to increments in endogenous parathyroid hormone is present in such patients. This abnormality is, at least partly, responsible for the hypocalcemia and secondary hyperparathyroidism of renal insufficiency.", "contents": "Skeletal resistance to endogenous parathyroid hormone in pateints with early renal failure. A possible cause for secondary hyperparathyroidism. Studies were carried out to evaluate whether skeletal resistance to acute increments in endogenous parathyroid hormone exists in patients with mild to moderate renal insufficiency. Hypocalcemia was induced with the infusion of ethyl-enediamine-tetra-acetate (EDTA) in 10 normal subjects and 13 patients with mild renal failure. After the induction of hypocalcemia, the concentration of serum calcium increased gradually and reached preinfusion levels by 22 h in the normal subjects; in contrast, the levels of serum calcium in patients with mild renal insufficiency were significantly lower than the preinfusion values even at the end of 26 h following the EDTA infusion. This delayed recovery occurred despite significantly higher levels of serum immunoreactive parathyroid hormone (IPTH) in the patients than in the normal subjects. The increase in the levels of IPTH reflect elevations in the concentrations of biologically active hormone since urinary cyclic AMP increased significantly. Urinary calcium excretion following the EDTA infusion was not different in both groups and, therefore, could not account for the delayed recovery of serum calcium values in the patients with renal insufficiency. These results indicate that secondary hyperparathyroidism exists early in patients with renal failure and such patients have exaggerated parathyroid hormone secretion in response to acute hypocalcemia. The data are consistent with the concept that skeletal resistance to increments in endogenous parathyroid hormone is present in such patients. This abnormality is, at least partly, responsible for the hypocalcemia and secondary hyperparathyroidism of renal insufficiency."} {"id": "PMID:169281", "title": "Effects of progestins on estradiol receptor levels in human endometrium.", "content": "Medroxyprogesterone acetate (Provera) was administered orally during 2-4 days to women undergoing endometrial curettage during the follicular phase of the menstrual cycle. Estradiol (E2) receptor levels were estimated from the amounts of 2H-E2 tightly bound in nuclei after incubation of endometrial tissue with an excess of the labeled hormone. An average value (9 subjects) of 1.5 pmole E2/mg DNA +/- 0.7 (mean +1- SD) was found. This value is significantly lower than the average E2 receptor levels in proliferative endometrium of untreated subjects (3.2 +/- 1.3, n = 33) and equals the level observed in the early secretory phase (1.5 +/- 0.5, n = 5). These results indicate that one of the progestin effects on human endometrium is the reduction of E2 receptor levels.", "contents": "Effects of progestins on estradiol receptor levels in human endometrium. Medroxyprogesterone acetate (Provera) was administered orally during 2-4 days to women undergoing endometrial curettage during the follicular phase of the menstrual cycle. Estradiol (E2) receptor levels were estimated from the amounts of 2H-E2 tightly bound in nuclei after incubation of endometrial tissue with an excess of the labeled hormone. An average value (9 subjects) of 1.5 pmole E2/mg DNA +/- 0.7 (mean +1- SD) was found. This value is significantly lower than the average E2 receptor levels in proliferative endometrium of untreated subjects (3.2 +/- 1.3, n = 33) and equals the level observed in the early secretory phase (1.5 +/- 0.5, n = 5). These results indicate that one of the progestin effects on human endometrium is the reduction of E2 receptor levels."} {"id": "PMID:169282", "title": "Evidence for partial 21-hydroxylase deficiency among heterozygote carriers of congenital adrenal hyperplasia.", "content": "Concentrations of 17-hydroxyprogesterone are significantly greater in heterozygous carriers of CVAH than in controls 30 and 60 minutes after an infusion of 25 units of synthetic ACTH 1-24 and 2 hours after beginning a 4-hour infusion of 50 units ACTH. The majority of carriers were clearly above the control range at these collection times. Hence, heterozygous carriers have a partial enzyme deficiency although all cannot be diagnosed based on 17-hydroxyprogesterone levels after ACTH stimulation.", "contents": "Evidence for partial 21-hydroxylase deficiency among heterozygote carriers of congenital adrenal hyperplasia. Concentrations of 17-hydroxyprogesterone are significantly greater in heterozygous carriers of CVAH than in controls 30 and 60 minutes after an infusion of 25 units of synthetic ACTH 1-24 and 2 hours after beginning a 4-hour infusion of 50 units ACTH. The majority of carriers were clearly above the control range at these collection times. Hence, heterozygous carriers have a partial enzyme deficiency although all cannot be diagnosed based on 17-hydroxyprogesterone levels after ACTH stimulation."} {"id": "PMID:169283", "title": "Pattern of plasma ACTH, hGH, and cortisol during menstrual cycle.", "content": "The pattern of secretion of plasma ACTH, hGH, TSH, LH, FSH and cortisol was studied in 12 menstrual cycles, representing 5 normal volunteers. Results were plotted by taking the LH-FSH midcycle peak as day 0. The typical menstrual cyclic LH and FSH pattern was observed in each case. ACTH, cortisol and hGH varied significantly throughout the menstrual cycle. ACTH was characterized by a decrease during the follicular phase, a nadir at day -2, followed by a significant increase to a peak at day 0, then a subsequent decrease and constant levels during the luteal phase until day +8. Cortisol was lowest in the follicular phase until day -4, and highest from day -2 to day 0. During the luteal phase, cortisol remained constant but was significantly higher than in the follicular phase (days -7 to -4). hGH showed a significant increase during the periovulatory period (days -3 to +3). No significant changes of plasma TSH were observed. These results suggest that pituitary hormones other than gonadotropins may be involved in the ovulatory mechanism, and reveal a degree of stimulation of the pituitary-adrenal axis without establishing whether the effect is direct or indirect.", "contents": "Pattern of plasma ACTH, hGH, and cortisol during menstrual cycle. The pattern of secretion of plasma ACTH, hGH, TSH, LH, FSH and cortisol was studied in 12 menstrual cycles, representing 5 normal volunteers. Results were plotted by taking the LH-FSH midcycle peak as day 0. The typical menstrual cyclic LH and FSH pattern was observed in each case. ACTH, cortisol and hGH varied significantly throughout the menstrual cycle. ACTH was characterized by a decrease during the follicular phase, a nadir at day -2, followed by a significant increase to a peak at day 0, then a subsequent decrease and constant levels during the luteal phase until day +8. Cortisol was lowest in the follicular phase until day -4, and highest from day -2 to day 0. During the luteal phase, cortisol remained constant but was significantly higher than in the follicular phase (days -7 to -4). hGH showed a significant increase during the periovulatory period (days -3 to +3). No significant changes of plasma TSH were observed. These results suggest that pituitary hormones other than gonadotropins may be involved in the ovulatory mechanism, and reveal a degree of stimulation of the pituitary-adrenal axis without establishing whether the effect is direct or indirect."} {"id": "PMID:169284", "title": "Radioreceptor assay of insulin: Comparison of plasma and pancreatic insulins and proinsulins.", "content": "Porcine proinsulin, related intermediates and plasma immunoreactive insulin components have been studied by radioreceptor assay. Using the purified rat liver membrane or cultured human lymphocyte radioreceptor assay, porcine proinsulin is %5, split proinsulin 6% (54-55 split in connecting peptide) desdipeptide proinsulin 20% (deletion of amino acids 62 and 63 of connecting peptide) and desnonapeptide proinsulin 27% (deletion of amino acids 55-63 of connecting peptide) as active as porcine insulin in both assay systems; these values closely parallel the in vitro bioactivity of these preparations. In the lymphocyte radioreceptor assay the human plasma immunoreactive insulin-like component has the same potency as porcine insulin per immunoreactive unit, whereas the plasma immunoreactive proinsulin-like component is only 15% as active. Since both plasma immunoreactive components are somewhat less reactive than would be expected from puriified human insulin and proinsulin, the data suggest that both plasma components contain immunoreactive molecules that do not react in the radioreceptor assay.", "contents": "Radioreceptor assay of insulin: Comparison of plasma and pancreatic insulins and proinsulins. Porcine proinsulin, related intermediates and plasma immunoreactive insulin components have been studied by radioreceptor assay. Using the purified rat liver membrane or cultured human lymphocyte radioreceptor assay, porcine proinsulin is %5, split proinsulin 6% (54-55 split in connecting peptide) desdipeptide proinsulin 20% (deletion of amino acids 62 and 63 of connecting peptide) and desnonapeptide proinsulin 27% (deletion of amino acids 55-63 of connecting peptide) as active as porcine insulin in both assay systems; these values closely parallel the in vitro bioactivity of these preparations. In the lymphocyte radioreceptor assay the human plasma immunoreactive insulin-like component has the same potency as porcine insulin per immunoreactive unit, whereas the plasma immunoreactive proinsulin-like component is only 15% as active. Since both plasma immunoreactive components are somewhat less reactive than would be expected from puriified human insulin and proinsulin, the data suggest that both plasma components contain immunoreactive molecules that do not react in the radioreceptor assay."} {"id": "PMID:169285", "title": "Potentiation of adrenocortical response upon intermittent stimulation with corticotropin in normal subjects.", "content": "Modifications of adrenocortical steroidogenic response to ACTH as a consequence of acute prior exposure to this hormone, were studied in 106 normal subjects divided in 15 experimental groups. Adrenocortical response was assessed by the changes in plasma cortisol level and in urinary excretion of cortisol, 17-ketogenic and 17-ketosteroids; in some experiments plasma 11-deoxycortisol, corticosterone, progesterone and 17-hydroxyprogesterone were determined as well, together with urinary excretion of the unconjugated form of 11-deoxycortisol and corticosterone. Slow (8-h) intravenous administration of ACTH in amounts producing maximal response, leaves the adrenal cortex in a hyperresponsive state in case of further stimulation for up to 3 days, while the adrenocortical secretion comes back to baseline in the meantime. This potentiation phenomenon seems to concern essentially cortisol secretion since, among the compounds measured only cortisol and 11-deoxycortisol secretions increased progressively in amplitude when ACTH was administered repeatedly. Futhermore the degree of ACTH-induced adrenocortical hyperresponsiveness was found to depend on the amount of ACTH injected and on the time during which the adrenal cells are exposed to high peptide hormone concentrations. Increased adrenocortical responsiveness to ACTH persists when endogenous corticotropin secretion was suppressed for a few days by dexamethasone in normal subjects. Thus the potentiation phenomenon is not critically dependent on continued exposure of adrenal cells to endogenous corticotropin.", "contents": "Potentiation of adrenocortical response upon intermittent stimulation with corticotropin in normal subjects. Modifications of adrenocortical steroidogenic response to ACTH as a consequence of acute prior exposure to this hormone, were studied in 106 normal subjects divided in 15 experimental groups. Adrenocortical response was assessed by the changes in plasma cortisol level and in urinary excretion of cortisol, 17-ketogenic and 17-ketosteroids; in some experiments plasma 11-deoxycortisol, corticosterone, progesterone and 17-hydroxyprogesterone were determined as well, together with urinary excretion of the unconjugated form of 11-deoxycortisol and corticosterone. Slow (8-h) intravenous administration of ACTH in amounts producing maximal response, leaves the adrenal cortex in a hyperresponsive state in case of further stimulation for up to 3 days, while the adrenocortical secretion comes back to baseline in the meantime. This potentiation phenomenon seems to concern essentially cortisol secretion since, among the compounds measured only cortisol and 11-deoxycortisol secretions increased progressively in amplitude when ACTH was administered repeatedly. Futhermore the degree of ACTH-induced adrenocortical hyperresponsiveness was found to depend on the amount of ACTH injected and on the time during which the adrenal cells are exposed to high peptide hormone concentrations. Increased adrenocortical responsiveness to ACTH persists when endogenous corticotropin secretion was suppressed for a few days by dexamethasone in normal subjects. Thus the potentiation phenomenon is not critically dependent on continued exposure of adrenal cells to endogenous corticotropin."} {"id": "PMID:169286", "title": "Radioreceptor-inactive growth hormone associated with stimulated secretion in normal subjects.", "content": "We have previously reported systematic discrepancies between radioreceptor (RRA) and radioimmunoassay (RIA) measurements of growth hormone (hGH) in acromegalic patients. Due to limitations in RRA sensitivity, such comparisons could not be made in normal subjects. RRA methodology has now been adapted to allow detection of hGH at normal circulating levels. Since variations in Na+, K+, Ca++, and Mg++, incubation at 37 C and 4 C, and delayed tracer addition failed to improve assay sensitivity, specimen size was increased to 300 mul and incubation volume to 1.5 ml, while holding the quantity of added receptor constant. Best assay sensitivity, in room temperature incubations in 25 mM Tris for 16 h at pH 7.6 and 10 mM Ca++, was 0.66 +/- 0.30 ng hGH per ml serum. Under these conditions, 200 mug hepatic receptor protein bount 15.8 +/- 0.83% of added 125I-hGH, and 8.72 +/- 0.85% of bound tracer was displaced by 0.25 ng added unlabeled hGH. Nonspecific depression of binding by serum did not impair assay sensitivity with most receptor preparations. The basal hGH measured by RIA (antiserum 68-416) in a group of normal short children was 1.97 ng/ml, similar to the RRA result, 1.89 ng/ml (P = NS). Comparative measurements were also made in selected samples of sufficient volume during the 1 1/2 h following administration of hGH secretagogues (insulin, arginine, L-dopa). In these samples, the RIA value was 9.34 +/- 0.68 and the RRA value 6.29 +/- 0.62 ng/ml (P less than 0.01); the RIA/RRA was 1.77 +/- 0.18. Thus, no significant measurement discrepancy was found in basal samples from normal subjects, in contrast to previous findings in acromegalics. The appearance of such a discrepancy within 90 min after stimulation of hGH might be due to RIA/RRA discordance in secreted molecular subspecies, or might arise from peripheral hGH metabolism.", "contents": "Radioreceptor-inactive growth hormone associated with stimulated secretion in normal subjects. We have previously reported systematic discrepancies between radioreceptor (RRA) and radioimmunoassay (RIA) measurements of growth hormone (hGH) in acromegalic patients. Due to limitations in RRA sensitivity, such comparisons could not be made in normal subjects. RRA methodology has now been adapted to allow detection of hGH at normal circulating levels. Since variations in Na+, K+, Ca++, and Mg++, incubation at 37 C and 4 C, and delayed tracer addition failed to improve assay sensitivity, specimen size was increased to 300 mul and incubation volume to 1.5 ml, while holding the quantity of added receptor constant. Best assay sensitivity, in room temperature incubations in 25 mM Tris for 16 h at pH 7.6 and 10 mM Ca++, was 0.66 +/- 0.30 ng hGH per ml serum. Under these conditions, 200 mug hepatic receptor protein bount 15.8 +/- 0.83% of added 125I-hGH, and 8.72 +/- 0.85% of bound tracer was displaced by 0.25 ng added unlabeled hGH. Nonspecific depression of binding by serum did not impair assay sensitivity with most receptor preparations. The basal hGH measured by RIA (antiserum 68-416) in a group of normal short children was 1.97 ng/ml, similar to the RRA result, 1.89 ng/ml (P = NS). Comparative measurements were also made in selected samples of sufficient volume during the 1 1/2 h following administration of hGH secretagogues (insulin, arginine, L-dopa). In these samples, the RIA value was 9.34 +/- 0.68 and the RRA value 6.29 +/- 0.62 ng/ml (P less than 0.01); the RIA/RRA was 1.77 +/- 0.18. Thus, no significant measurement discrepancy was found in basal samples from normal subjects, in contrast to previous findings in acromegalics. The appearance of such a discrepancy within 90 min after stimulation of hGH might be due to RIA/RRA discordance in secreted molecular subspecies, or might arise from peripheral hGH metabolism."} {"id": "PMID:169287", "title": "Circulating NSILA-s in man: Preliminary studies of stimuli in vivo and of binding to plasma components.", "content": "The insulin-like peptide NSILA-s (non-suppressible insulin-like activity soluble in acid ethanol) was measured in plasma using gel filtration in acid and a new radioreceptor assay. Total plasma NSILA-s levels, which are elevated in some patients with extrapancreatic tumors and hypoglycemia, were also found to be elevated in pregnancy. Patients with hypopituitarism had subnormal concentrations of total plasma NSILA-s which rose promptly and reached a peak 1 h after intravenous hGH. In contrast ot this acute stimulus, chronic elevation of hGH resulted in an elevated level of NSILA-s in only 1 of 10 acromegalics. In normal subjects, oral glucose loading resulted in a rise in NSILA-s (mean peak equals 151% of basal) while insulin induced hypoglycemia produced a small and variable fall. Among the other conditions studied, anorexia nervosa was associated with low levels of NSILA-s. Using gel filtration we found that at physiologic pH about 93% of endogenous NSILA-s is reversibly bound to larger molecules. We show that in normal adults the insulin-like bioactivity in plasma due to free NSILA-s in the basal state is equal to that exerted by insulin itself, and that the free NSILA-s in the circulation of patients with extra-pancreatic tumors approximates the elevated level of insulin in patients with insulin-secreting pancreatic tumors.", "contents": "Circulating NSILA-s in man: Preliminary studies of stimuli in vivo and of binding to plasma components. The insulin-like peptide NSILA-s (non-suppressible insulin-like activity soluble in acid ethanol) was measured in plasma using gel filtration in acid and a new radioreceptor assay. Total plasma NSILA-s levels, which are elevated in some patients with extrapancreatic tumors and hypoglycemia, were also found to be elevated in pregnancy. Patients with hypopituitarism had subnormal concentrations of total plasma NSILA-s which rose promptly and reached a peak 1 h after intravenous hGH. In contrast ot this acute stimulus, chronic elevation of hGH resulted in an elevated level of NSILA-s in only 1 of 10 acromegalics. In normal subjects, oral glucose loading resulted in a rise in NSILA-s (mean peak equals 151% of basal) while insulin induced hypoglycemia produced a small and variable fall. Among the other conditions studied, anorexia nervosa was associated with low levels of NSILA-s. Using gel filtration we found that at physiologic pH about 93% of endogenous NSILA-s is reversibly bound to larger molecules. We show that in normal adults the insulin-like bioactivity in plasma due to free NSILA-s in the basal state is equal to that exerted by insulin itself, and that the free NSILA-s in the circulation of patients with extra-pancreatic tumors approximates the elevated level of insulin in patients with insulin-secreting pancreatic tumors."} {"id": "PMID:169288", "title": "The effect of iodized oil on the TSH response to TRH in endemic goiter patients.", "content": "The TSH and T3 response to synthetic TRH was evaluated in 4 groups of patients: normal controls and goitrous subjects from the urban area of Sao Paulo (urinary iodine excretion: 172.2 +/- 48.3 mug I/g creatinine) and nongoitrous and goitrous subjects from the endemic areas of Sao Bento (urinary iodine excretion: 53.8 +/- 17.1 mug I/g). Plasma T4 and T3 were within our normal range in all groups of patients. The mean plasma TSH was significantly higher (5.2 +/- 3.3 muU/ml) in goitrous subjects living in Sao Bento as compared to normal control groups both in urban or endemic areas, and after TRH these patients had an exaggerated and sustained TSH response with a significantly higher peak level (21.1 +/- 7.9 muU/ml). T3 concentration rose in all subjects following TRH and all patients from the Sao Bento endemic areas had a significantly higher proportionate increase in plasma T3 at 120 min. After an injection of iodized oil basal plasma TSH returned to the normal range in the goitrous subjects from Sao Bento. The mean peak TSH response to TRH was 9.1 +/- 3.8 muU/ml at 3 months after the iodized oil injection, and only at 6 months after the iodized oil TSH response was significantly reduced (peak level: 6.1 +/- 2.4 muU/ml). It is confirmed that plasma TSH levels are increased in endemic goitrous patients but not in normal controls living in the same endemic area and it is suggested that the pituitary threshold for inhibition of secretion of TSH by T4 and T3 has been reset in these goitrous subjects to achieve a persistently higher secretion rate of TSH.", "contents": "The effect of iodized oil on the TSH response to TRH in endemic goiter patients. The TSH and T3 response to synthetic TRH was evaluated in 4 groups of patients: normal controls and goitrous subjects from the urban area of Sao Paulo (urinary iodine excretion: 172.2 +/- 48.3 mug I/g creatinine) and nongoitrous and goitrous subjects from the endemic areas of Sao Bento (urinary iodine excretion: 53.8 +/- 17.1 mug I/g). Plasma T4 and T3 were within our normal range in all groups of patients. The mean plasma TSH was significantly higher (5.2 +/- 3.3 muU/ml) in goitrous subjects living in Sao Bento as compared to normal control groups both in urban or endemic areas, and after TRH these patients had an exaggerated and sustained TSH response with a significantly higher peak level (21.1 +/- 7.9 muU/ml). T3 concentration rose in all subjects following TRH and all patients from the Sao Bento endemic areas had a significantly higher proportionate increase in plasma T3 at 120 min. After an injection of iodized oil basal plasma TSH returned to the normal range in the goitrous subjects from Sao Bento. The mean peak TSH response to TRH was 9.1 +/- 3.8 muU/ml at 3 months after the iodized oil injection, and only at 6 months after the iodized oil TSH response was significantly reduced (peak level: 6.1 +/- 2.4 muU/ml). It is confirmed that plasma TSH levels are increased in endemic goitrous patients but not in normal controls living in the same endemic area and it is suggested that the pituitary threshold for inhibition of secretion of TSH by T4 and T3 has been reset in these goitrous subjects to achieve a persistently higher secretion rate of TSH."} {"id": "PMID:169289", "title": "Effect of the diphosphonate EHDP on bone mineral metabolism during prolonged bed rest.", "content": "The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.", "contents": "Effect of the diphosphonate EHDP on bone mineral metabolism during prolonged bed rest. The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses."} {"id": "PMID:169290", "title": "Increase in numbers of gonadotropin receptors on granulosa cells during follicle maturation.", "content": "The binding of both human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) to a homogeneous population of isolated intact granulosa cells from increasingly mature porcine ovaan follicles has been studied. The number of receptor sites per granulosa cell increases 35-fold as the follicle enlarges, although cell size remains constant. This may explain the increased biologic responsiveness to gonadotropin of mature cells from large follicles. The affinity for both hormones, as determined by equilibrium dissociation constants, is high, and does not appear to change significantly as the cells mature. Comparison of dissociation constants, numbers of binding sites, and competitive inhibition between hCH and hLH, indicates that these two hormones probably interact with the same receptor on the granulosa cells.", "contents": "Increase in numbers of gonadotropin receptors on granulosa cells during follicle maturation. The binding of both human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) to a homogeneous population of isolated intact granulosa cells from increasingly mature porcine ovaan follicles has been studied. The number of receptor sites per granulosa cell increases 35-fold as the follicle enlarges, although cell size remains constant. This may explain the increased biologic responsiveness to gonadotropin of mature cells from large follicles. The affinity for both hormones, as determined by equilibrium dissociation constants, is high, and does not appear to change significantly as the cells mature. Comparison of dissociation constants, numbers of binding sites, and competitive inhibition between hCH and hLH, indicates that these two hormones probably interact with the same receptor on the granulosa cells."} {"id": "PMID:169291", "title": "A radioreceptor assay for follicle-stimulating hormone.", "content": "A highly specific and sensitive radioreceptor assay for FSH has been developed, using partially purified plasma membranes from bovine testes. Highly purifed hFSH was radioiodinated by the lactoperoxidase method. The limit of detection of purified hFSH was 1 ng/ml on the basis of 2 times standard deviation of the zero value. The assay was applicable for measurements of FSH in serum; however, the sensitivity decreased slightly to 2.5 ng/ml. The precision of the assay was less than +/- 10% within-assays and +/- 15% between-assays as expressed by the coefficient of variation. The assay was highly specific for FSH of various species. Slight inhibition of uptake of 125I-hFSH was observed with LH and TSH; but no competition was seen with 10,000 ng/ml of insulin, prolactin, hGH, hCG, and subunits of LH. Purified hFSH (LER-1575C) was measured to be 200 times the potency of the reference FSH/LH (LER-907); and purified ovine FSH (LER-1491) and rat FSH (FSH-I-1) were estimated to be 35 times and 71 times that of oFSH-S-1 (NIH), respectively. The content of FSH in human pituitary was estimated to be 226.8 +/- 118.8 mIU/mg, and the index of discrimination (radioimmunoassay/radioreceptor assay) for pituitary FSH was demonstrated to be 1.71 +/- 0.49. For measurements of serum hFSH, the index of discrimination (radioimmunoassay/radioreceptor assay) was demonstrated to be 1.08 +/- 0.20.", "contents": "A radioreceptor assay for follicle-stimulating hormone. A highly specific and sensitive radioreceptor assay for FSH has been developed, using partially purified plasma membranes from bovine testes. Highly purifed hFSH was radioiodinated by the lactoperoxidase method. The limit of detection of purified hFSH was 1 ng/ml on the basis of 2 times standard deviation of the zero value. The assay was applicable for measurements of FSH in serum; however, the sensitivity decreased slightly to 2.5 ng/ml. The precision of the assay was less than +/- 10% within-assays and +/- 15% between-assays as expressed by the coefficient of variation. The assay was highly specific for FSH of various species. Slight inhibition of uptake of 125I-hFSH was observed with LH and TSH; but no competition was seen with 10,000 ng/ml of insulin, prolactin, hGH, hCG, and subunits of LH. Purified hFSH (LER-1575C) was measured to be 200 times the potency of the reference FSH/LH (LER-907); and purified ovine FSH (LER-1491) and rat FSH (FSH-I-1) were estimated to be 35 times and 71 times that of oFSH-S-1 (NIH), respectively. The content of FSH in human pituitary was estimated to be 226.8 +/- 118.8 mIU/mg, and the index of discrimination (radioimmunoassay/radioreceptor assay) for pituitary FSH was demonstrated to be 1.71 +/- 0.49. For measurements of serum hFSH, the index of discrimination (radioimmunoassay/radioreceptor assay) was demonstrated to be 1.08 +/- 0.20."} {"id": "PMID:169292", "title": "ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site.", "content": "The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity.", "contents": "ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site. The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity."} {"id": "PMID:169293", "title": "The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions.", "content": "The contribution of hydrogen peroxide (H2O2) and one of its unstable intermediates, superoxide anion (O2), to the oxidative reactions that occur in phagocytizing leukocytes was explored by depleting these cells of O2. This was accomplished by allowing them to phagocytize latex particles coated with superoxide dismutase (SOD), which catalyzes the generation of H2O2 from O2. Although the rate and extent of phagocytosis of latex coated with bovine serum albumin was similar to latex coated with SOD, the rate of oxygen consumption, [14C]formate oxidation, [1-14C]glucose oxidation, and iodination of zymosan particles was significantly enhanced by SOD. In contrast, the rate and extent of reduction of nitroblue tetrazolium (NBT) was diminished by 60%. These studies indicate that the majority of NBT reduction by leukocytes is due to O2, whereas stimulation of the hexose monophosphate shunt and iodination of ingested particles requires H2O2 generated from the increased reduction of oxygen by phagocytizing leukocytes.", "contents": "The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions. The contribution of hydrogen peroxide (H2O2) and one of its unstable intermediates, superoxide anion (O2), to the oxidative reactions that occur in phagocytizing leukocytes was explored by depleting these cells of O2. This was accomplished by allowing them to phagocytize latex particles coated with superoxide dismutase (SOD), which catalyzes the generation of H2O2 from O2. Although the rate and extent of phagocytosis of latex coated with bovine serum albumin was similar to latex coated with SOD, the rate of oxygen consumption, [14C]formate oxidation, [1-14C]glucose oxidation, and iodination of zymosan particles was significantly enhanced by SOD. In contrast, the rate and extent of reduction of nitroblue tetrazolium (NBT) was diminished by 60%. These studies indicate that the majority of NBT reduction by leukocytes is due to O2, whereas stimulation of the hexose monophosphate shunt and iodination of ingested particles requires H2O2 generated from the increased reduction of oxygen by phagocytizing leukocytes."} {"id": "PMID:169294", "title": "Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat.", "content": "The metabolism of intravenously injected large and small chylomicrons from intestinal lymph and of very low density lipoproteins from blood plasma was studied in functionally eviscerated \"supradiaphragmetic\" rats. For studies with lymph lipoproteins, recipient animals were injected with 4-amino-pyrazolopyrimidine 18 h before injection of lipoprotein to prevent secretion of very low density lipoproteins into their blood plasma. In all cases, most of the triglycerides (labeled with 14C) were rapidly metabolized, whereas cholesteryl esters (labeled with 3H) persisted in the blood. Most of the cholesteryl esters remained in smaller \"remnant\" lipoproteins, less dense that 1.006, which retained an apparently spherical shape, as determined by electron microscopy of negatively stained preparations. Whereas the diameters and chemical compositions of large chylomicrons were substantially different from those of small chylomicrons and very low density lipoproteins, all remnants were similar in these respects. Average remnant diameters were 400-600 A and remnants were enriched in cholesteryl esters and in protein insoluble in tetramethylurea. In addition to triglycerides, remnants were depleted of phospholiarticle size, the composition of remnants, like that of their precursors, was consistent with the \"pseudomicellar\" model of lipoproteins, in which a core of nonpolar lipids is covered by a monolayer of polar lipids and protein. These results domonstrate the fundamental similarity of the initial step in the metabolism of triglyceride-rich lipoproteins from intestinal mucosa and liver and show that loss of triglycerides from the core of the particles is accompanied by removal of polar components from the surface.", "contents": "Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat. The metabolism of intravenously injected large and small chylomicrons from intestinal lymph and of very low density lipoproteins from blood plasma was studied in functionally eviscerated \"supradiaphragmetic\" rats. For studies with lymph lipoproteins, recipient animals were injected with 4-amino-pyrazolopyrimidine 18 h before injection of lipoprotein to prevent secretion of very low density lipoproteins into their blood plasma. In all cases, most of the triglycerides (labeled with 14C) were rapidly metabolized, whereas cholesteryl esters (labeled with 3H) persisted in the blood. Most of the cholesteryl esters remained in smaller \"remnant\" lipoproteins, less dense that 1.006, which retained an apparently spherical shape, as determined by electron microscopy of negatively stained preparations. Whereas the diameters and chemical compositions of large chylomicrons were substantially different from those of small chylomicrons and very low density lipoproteins, all remnants were similar in these respects. Average remnant diameters were 400-600 A and remnants were enriched in cholesteryl esters and in protein insoluble in tetramethylurea. In addition to triglycerides, remnants were depleted of phospholiarticle size, the composition of remnants, like that of their precursors, was consistent with the \"pseudomicellar\" model of lipoproteins, in which a core of nonpolar lipids is covered by a monolayer of polar lipids and protein. These results domonstrate the fundamental similarity of the initial step in the metabolism of triglyceride-rich lipoproteins from intestinal mucosa and liver and show that loss of triglycerides from the core of the particles is accompanied by removal of polar components from the surface."} {"id": "PMID:169295", "title": "Cryoimmunoglobulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis.", "content": "Cryogloculins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasuclitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vascultis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasclitis. Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM. A monoclonal rheumatoid factor did not detect 7S-ANTI-7S complexes in the cryoprecipitates, but acid eluates from some cryoglobulins absorbed with insoluble IgG revealed an antiglobulin of the IgG class. Serial studies performed on vasculitis patients treated with cyclophosphamide disclosed a relationship between clinical evidence of vasculitis and the presence of cryoglobulins. The antigen (IgG) and antibody (largely IgM rheumatoid factor) nature of these cryglobulins is presented as evidence that the widespread vascular complications of RA are mediated, at least in part, by circulating immune complexes.", "contents": "Cryoimmunoglobulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis. Cryogloculins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasuclitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vascultis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasclitis. Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM. A monoclonal rheumatoid factor did not detect 7S-ANTI-7S complexes in the cryoprecipitates, but acid eluates from some cryoglobulins absorbed with insoluble IgG revealed an antiglobulin of the IgG class. Serial studies performed on vasculitis patients treated with cyclophosphamide disclosed a relationship between clinical evidence of vasculitis and the presence of cryoglobulins. The antigen (IgG) and antibody (largely IgM rheumatoid factor) nature of these cryglobulins is presented as evidence that the widespread vascular complications of RA are mediated, at least in part, by circulating immune complexes."} {"id": "PMID:169296", "title": "Insulin receptor deficiency in genetic and acquired obesity.", "content": "We have previously shown that in the insulin-resistant obese hyperglycemic mouse (ob/ob) there is a deficiency in the number of insulin receptor sites on hepatocytes, adipocytes, and thymic lymphocytes. We now find that concentration of insulin receptors on liver plasma membranes is decreased in the db/db mouse, another form of inherited obesity, and in normal mice that became obese after treatment with gold thioglucose, while thin mice, heterozygous for the ob mutation (ob/+), have normal insulin binding. With acute and chronic food restriction of the ob/ob and gold thioglucose obese mice, there is reduction in hyperinsulinemia and an associated increase in the insulin receptor concentration toward normal. In contrast, when fasting ob/ob mice were given exogenous insulin to maintain the hyperinsulinemia, insulin receptors failed to increase. Thus, in all cases, there was a consistent relationship between the degree of hyperinsulinemia and of insulin receptor loss. These findings suggest that decreased insulin binding is a characteristic feature of the insulin resistance of obesity, and that sustained hyperinsulinemia is a major factor in the control of the concentration of insulin receptors on target cells.", "contents": "Insulin receptor deficiency in genetic and acquired obesity. We have previously shown that in the insulin-resistant obese hyperglycemic mouse (ob/ob) there is a deficiency in the number of insulin receptor sites on hepatocytes, adipocytes, and thymic lymphocytes. We now find that concentration of insulin receptors on liver plasma membranes is decreased in the db/db mouse, another form of inherited obesity, and in normal mice that became obese after treatment with gold thioglucose, while thin mice, heterozygous for the ob mutation (ob/+), have normal insulin binding. With acute and chronic food restriction of the ob/ob and gold thioglucose obese mice, there is reduction in hyperinsulinemia and an associated increase in the insulin receptor concentration toward normal. In contrast, when fasting ob/ob mice were given exogenous insulin to maintain the hyperinsulinemia, insulin receptors failed to increase. Thus, in all cases, there was a consistent relationship between the degree of hyperinsulinemia and of insulin receptor loss. These findings suggest that decreased insulin binding is a characteristic feature of the insulin resistance of obesity, and that sustained hyperinsulinemia is a major factor in the control of the concentration of insulin receptors on target cells."} {"id": "PMID:169297", "title": "Effect of Klebsiella pneumoniae enterotoxin on intestinal transport in the rat.", "content": "The effects on intestinal transport of either a semipurified preparation of enterotoxin elaborated by Klebsiella pneumoniae or similaryly prepared control material were tested by marker perfusion studies in the small intestine of rats. At a concentration of 2 mg/ml, the enterotoxin produced net secretion of water, Na, and Cl in both jejunal and ileal segments; HCO3 transport was not affected. Net secretion was evident within 30 min after intorduction of the toxin and was maximal after 90 min. The addition of 56 mM glucose to the enterotoxin-containing perfusion fluid resulted in reversal of water and Na transport to net absorption in both intestinal segments. The enterotoxin also produced a significant depression of xylose absorption in both the jejunum and ileum but did not affect the absorption of either glucose or L-leucine. Intestinal structure was not altered after perfusion of the toxin but insillation of approximately one-quarter of the total perfusion dose into a ligated jejunal loop for 18 h produced fluid secretion and structural abnormalities. These observations confirm the fact that other species of coliform bacteria in addition to tescherichia coli are capable of elaborating an enterotoxin. Such species commonly contaminate the small intestine of persons with tropical sprue and it is suggested that chronic exposure of the intestinal mucosa to the enterotoxin elaborated by these bacteria may be a factor in the pathogenesis of intestinal abnormalities in thid disorder.", "contents": "Effect of Klebsiella pneumoniae enterotoxin on intestinal transport in the rat. The effects on intestinal transport of either a semipurified preparation of enterotoxin elaborated by Klebsiella pneumoniae or similaryly prepared control material were tested by marker perfusion studies in the small intestine of rats. At a concentration of 2 mg/ml, the enterotoxin produced net secretion of water, Na, and Cl in both jejunal and ileal segments; HCO3 transport was not affected. Net secretion was evident within 30 min after intorduction of the toxin and was maximal after 90 min. The addition of 56 mM glucose to the enterotoxin-containing perfusion fluid resulted in reversal of water and Na transport to net absorption in both intestinal segments. The enterotoxin also produced a significant depression of xylose absorption in both the jejunum and ileum but did not affect the absorption of either glucose or L-leucine. Intestinal structure was not altered after perfusion of the toxin but insillation of approximately one-quarter of the total perfusion dose into a ligated jejunal loop for 18 h produced fluid secretion and structural abnormalities. These observations confirm the fact that other species of coliform bacteria in addition to tescherichia coli are capable of elaborating an enterotoxin. Such species commonly contaminate the small intestine of persons with tropical sprue and it is suggested that chronic exposure of the intestinal mucosa to the enterotoxin elaborated by these bacteria may be a factor in the pathogenesis of intestinal abnormalities in thid disorder."} {"id": "PMID:169298", "title": "Thrombin-induced protein phosphorylation in human platelets.", "content": "Intact human platelets loaded with 32PO4 contain multiple phosphorylated proteins. Thrombin treatment of intact 32PO4-loaded platelets results in a 2-6-fold increase in phosphorylation of a platelet protein (designated \"peak 7\" protein) of approximately 40,000 mol wt as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by gel filtration on Sephadex G-150. A similar increase in phosphorylation was observed in a platelet protein (designated \"peak 9\" protein) of approximately 20,000 mol wt. The time for half-maximal phosphorylation of peak 7 and peak 9 protein was 10-14 s. The concentration of thrombin at half-maximal phosphorylation was 0.25 U/ml for both proteins. Prior incubation of platelets with dibutyryl cyclic adenosine 3',5'-monophosphate or prostaglandin E1 inhibited thrombin-induced peak 7 and peak 9 protein phosphorylation. The erythroagglutinating phytohemagglutinin of Phaseolus vulgaris, a non-proteolytic release-inducing agent, induced peak 7 and peak 9 protein phosphorylation. Thus, the characteristics of peak 7 and peak 9 protein phosphorylation are similar to those of the platelet release reaction, suggesting that the phosphorylation of these proteins may play a role in the platelet release reaction. When platelet sonicates or the supernatant fraction from platelet sonicates were incubated with [gamma-32P]ATP there was phosphorylation of both peak 7 and peak 9 proteins. This phosphorylation was unaffected by either added thrombin or adenosine 3',5'-cyclic monophosphate (cAMP) despite the presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. Thus, the thrombin-dependent phosphorylation depends upon intact platelets. When the supernatant fraction from platelet sonicates was fractionated by histone-Sepharose affinity chromatography, two distinct protein kinase enzymes were resolved, one a cAMP-dependent holoenzyme and the other a cAMP-independent enzyme. The isolated cAMP-dependent enzyme fraction catalyzed the cAMP-(but not thrombin-) stimulated phosphorylation of a protein that co-electrophoresed with peak 7 protein.", "contents": "Thrombin-induced protein phosphorylation in human platelets. Intact human platelets loaded with 32PO4 contain multiple phosphorylated proteins. Thrombin treatment of intact 32PO4-loaded platelets results in a 2-6-fold increase in phosphorylation of a platelet protein (designated \"peak 7\" protein) of approximately 40,000 mol wt as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by gel filtration on Sephadex G-150. A similar increase in phosphorylation was observed in a platelet protein (designated \"peak 9\" protein) of approximately 20,000 mol wt. The time for half-maximal phosphorylation of peak 7 and peak 9 protein was 10-14 s. The concentration of thrombin at half-maximal phosphorylation was 0.25 U/ml for both proteins. Prior incubation of platelets with dibutyryl cyclic adenosine 3',5'-monophosphate or prostaglandin E1 inhibited thrombin-induced peak 7 and peak 9 protein phosphorylation. The erythroagglutinating phytohemagglutinin of Phaseolus vulgaris, a non-proteolytic release-inducing agent, induced peak 7 and peak 9 protein phosphorylation. Thus, the characteristics of peak 7 and peak 9 protein phosphorylation are similar to those of the platelet release reaction, suggesting that the phosphorylation of these proteins may play a role in the platelet release reaction. When platelet sonicates or the supernatant fraction from platelet sonicates were incubated with [gamma-32P]ATP there was phosphorylation of both peak 7 and peak 9 proteins. This phosphorylation was unaffected by either added thrombin or adenosine 3',5'-cyclic monophosphate (cAMP) despite the presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. Thus, the thrombin-dependent phosphorylation depends upon intact platelets. When the supernatant fraction from platelet sonicates was fractionated by histone-Sepharose affinity chromatography, two distinct protein kinase enzymes were resolved, one a cAMP-dependent holoenzyme and the other a cAMP-independent enzyme. The isolated cAMP-dependent enzyme fraction catalyzed the cAMP-(but not thrombin-) stimulated phosphorylation of a protein that co-electrophoresed with peak 7 protein."} {"id": "PMID:169303", "title": "The significance of inhibitor-resistant alkaline phosphatase in the cytochemical demonstration of transport adenosine triphosphatase.", "content": "The hydrolysis of disodium p-nitrophenyl phosphate at pH 9.0 by slices of formaldehydee-fixed rat renal cortex was investigated by colorimetric estimation of the nitrophenol liberated. It was found that three types of activity could be identified on the basis of their responses to inhibitors and cations: (a) alkaline phosphatase sensitive to inhibition by L-tetramisole; (b) potassium-dependent phosphatase, probably identifiable with the phosphatase component of sodium-potassium-dependent transport adenosine triphosphatase (?Na-K-ATPase); and (c) alkaline phosphatase insensitive to L-tetramisole. It was found that in the presence of strontium ions, as used in Na-K-ATPase cytochemistry, the activities of the second and third types of enzyme were approximately equal. The implications of these findings for the cytochemical demonstration of Na-K-ATPase are discussed.", "contents": "The significance of inhibitor-resistant alkaline phosphatase in the cytochemical demonstration of transport adenosine triphosphatase. The hydrolysis of disodium p-nitrophenyl phosphate at pH 9.0 by slices of formaldehydee-fixed rat renal cortex was investigated by colorimetric estimation of the nitrophenol liberated. It was found that three types of activity could be identified on the basis of their responses to inhibitors and cations: (a) alkaline phosphatase sensitive to inhibition by L-tetramisole; (b) potassium-dependent phosphatase, probably identifiable with the phosphatase component of sodium-potassium-dependent transport adenosine triphosphatase (?Na-K-ATPase); and (c) alkaline phosphatase insensitive to L-tetramisole. It was found that in the presence of strontium ions, as used in Na-K-ATPase cytochemistry, the activities of the second and third types of enzyme were approximately equal. The implications of these findings for the cytochemical demonstration of Na-K-ATPase are discussed."} {"id": "PMID:169304", "title": "Use of the unlabeled antibody immunohistochemical technique for the detection of human antibody.", "content": "Two methods have been developed which permit use of the unlabeled antibody immunohistochemical technique for detection of human antibody, without the need for immunization of humans with peroxidase. Human antibody to herpes simplex virus (HSV) reacted with human cell cultures infected with HSV was the experimental system. In the first method an attempt was made to employ rabbit peroxidase-antiperoxidase (PAP) soluble complexes in connectin with human antibody. This was done by sequential addition to the HSV-infected cells of (a) human anti-HSV, (b) rabbit antihuman globulin, (c) guinea pig antirabbit globulin (the bridging reagent) and (d) rabbit PAP. Strong specific staining of HSV-infected cells was obtained; however, difficulties were encountered with nonspecific reactions on uninfected cells. In the second method PAP soluble complexes prepared with baboon antiperoxidase were bridged to the human anti-HSV antibody by rabbit antihuman globulin. Because of the phylogenetic relatedness of human and baboon globulins this resulted in firm binding which gave strong specific staining of HSV-infected cells without significant reaction in uninfected cells.", "contents": "Use of the unlabeled antibody immunohistochemical technique for the detection of human antibody. Two methods have been developed which permit use of the unlabeled antibody immunohistochemical technique for detection of human antibody, without the need for immunization of humans with peroxidase. Human antibody to herpes simplex virus (HSV) reacted with human cell cultures infected with HSV was the experimental system. In the first method an attempt was made to employ rabbit peroxidase-antiperoxidase (PAP) soluble complexes in connectin with human antibody. This was done by sequential addition to the HSV-infected cells of (a) human anti-HSV, (b) rabbit antihuman globulin, (c) guinea pig antirabbit globulin (the bridging reagent) and (d) rabbit PAP. Strong specific staining of HSV-infected cells was obtained; however, difficulties were encountered with nonspecific reactions on uninfected cells. In the second method PAP soluble complexes prepared with baboon antiperoxidase were bridged to the human anti-HSV antibody by rabbit antihuman globulin. Because of the phylogenetic relatedness of human and baboon globulins this resulted in firm binding which gave strong specific staining of HSV-infected cells without significant reaction in uninfected cells."} {"id": "PMID:169306", "title": "Epidermal activity of NAD-dependent isocitrate dehydrogenase in psoriasis during treatment with dithranol.", "content": "The activity of ICDH(NAD) was measured in subcorneal and basal epidermal layers in 8 patients with psoriasis and in 7 healthy controls treated once a day with 0.15% dithranol in white petrolatum for 2 weeks. Skin biopsies were taken before and on days 2, 6, and 14 of the treatment. Lowry's microtechniques were used in conjunction with a bioluminescent system (bacterial luciferase) for enzymatic assays. The enzymic activity could be related to the type of keratinization present in the stratum corneum overlying the epidermal areas under study. In orthokeratotic areas from the controls, in noninvolved, and in treated involved skin the activity was low. In parakeratotic areas, as found in treated noninvolved and in involved psoriatic skin, the enzymic activity was increased to a level at least twice that found in orthokeratosis. Since ICDH(NAD) activity reflects an aspect of mitochondrial function, the results suggest that mitochondrial activity may be important in control of keratinization.", "contents": "Epidermal activity of NAD-dependent isocitrate dehydrogenase in psoriasis during treatment with dithranol. The activity of ICDH(NAD) was measured in subcorneal and basal epidermal layers in 8 patients with psoriasis and in 7 healthy controls treated once a day with 0.15% dithranol in white petrolatum for 2 weeks. Skin biopsies were taken before and on days 2, 6, and 14 of the treatment. Lowry's microtechniques were used in conjunction with a bioluminescent system (bacterial luciferase) for enzymatic assays. The enzymic activity could be related to the type of keratinization present in the stratum corneum overlying the epidermal areas under study. In orthokeratotic areas from the controls, in noninvolved, and in treated involved skin the activity was low. In parakeratotic areas, as found in treated noninvolved and in involved psoriatic skin, the enzymic activity was increased to a level at least twice that found in orthokeratosis. Since ICDH(NAD) activity reflects an aspect of mitochondrial function, the results suggest that mitochondrial activity may be important in control of keratinization."} {"id": "PMID:169308", "title": "Varicella-Zoster Immunoglobulins during Varicella, Latency, and Zoster.", "content": "Antibodies to membrane antigens of cells infected by varicella-zoster virus were detected by immunofluorescence. Rises in varicella-zoster IgA, IgG, and tigM were detected after both varicella and zoster. Prompt antibody responses were observed in patients with generalized zoster as well as in those with localized zoster. A delayed response was found, moreover, in one patient who did not develop disseminated disease. Antibody to varicella-zoster virus was detected in the sera of all three patients tested prior to and in all but one of 63 patients tested soon after onset of zoster. The level of varicella-zoster IgA and IgG rose in two of three immune patients after household exposure to infection with varicella-zoster virus. Varicella-zoster IgG was detected in the cord blood of infants whose mothers were immune to varicella.", "contents": "Varicella-Zoster Immunoglobulins during Varicella, Latency, and Zoster. Antibodies to membrane antigens of cells infected by varicella-zoster virus were detected by immunofluorescence. Rises in varicella-zoster IgA, IgG, and tigM were detected after both varicella and zoster. Prompt antibody responses were observed in patients with generalized zoster as well as in those with localized zoster. A delayed response was found, moreover, in one patient who did not develop disseminated disease. Antibody to varicella-zoster virus was detected in the sera of all three patients tested prior to and in all but one of 63 patients tested soon after onset of zoster. The level of varicella-zoster IgA and IgG rose in two of three immune patients after household exposure to infection with varicella-zoster virus. Varicella-zoster IgG was detected in the cord blood of infants whose mothers were immune to varicella."} {"id": "PMID:169309", "title": "Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody.", "content": "Factors that affect the spread of Streptococcus pneumoniae and the antibody responses associated with colonization were studied in 64 families for periods of eight to 52 weeks. Surveillance included daily recording of respiratory symptoms and bimonthly pharyngeal cultures for identification of the pneumococcal carrier state. Rhinovirus cultures were included for a portion of the study period. Intrafamilial carriage of a single type of S. pneumoniae and simultaneous spread to more than one family member were commonmspread often occurred in association with an upper respiratory tract infection; simultaneous transmission of S. pneumoniae and a rhinovirus was documented. Preexisting, type-specific serum antibody did not prevent acquisition of homotypic S. pneumoniae but did appear to shorten the duration of pharyngeal carriage. Sera of all 11 adults had greater than 150 ng of antibody nitrogen/ml of homotypic serum antibody (measured by a radioimmunoassay) before colonization. In contrast, only one of 13 preschool children had homotypic antibody concentrations of this magnitude before colonization. A threefold or greater rise in the concentration of homotypic antibody occurred in 13 of 24 children (54%) after acquisition of S. pneumoniae; the increase in antibody concentration was associated with illness in six of the children. On the other hand, acquisition of S. pneumoniae in adults was not associated with an increase in concentration of homotypic serum antibody.", "contents": "Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody. Factors that affect the spread of Streptococcus pneumoniae and the antibody responses associated with colonization were studied in 64 families for periods of eight to 52 weeks. Surveillance included daily recording of respiratory symptoms and bimonthly pharyngeal cultures for identification of the pneumococcal carrier state. Rhinovirus cultures were included for a portion of the study period. Intrafamilial carriage of a single type of S. pneumoniae and simultaneous spread to more than one family member were commonmspread often occurred in association with an upper respiratory tract infection; simultaneous transmission of S. pneumoniae and a rhinovirus was documented. Preexisting, type-specific serum antibody did not prevent acquisition of homotypic S. pneumoniae but did appear to shorten the duration of pharyngeal carriage. Sera of all 11 adults had greater than 150 ng of antibody nitrogen/ml of homotypic serum antibody (measured by a radioimmunoassay) before colonization. In contrast, only one of 13 preschool children had homotypic antibody concentrations of this magnitude before colonization. A threefold or greater rise in the concentration of homotypic antibody occurred in 13 of 24 children (54%) after acquisition of S. pneumoniae; the increase in antibody concentration was associated with illness in six of the children. On the other hand, acquisition of S. pneumoniae in adults was not associated with an increase in concentration of homotypic serum antibody."} {"id": "PMID:169311", "title": "Experimental infection with herpes simplex virus type 2 in newborn rats: Effects of treatment with iododeoxyuridine and cytosine arabinoside.", "content": "Sprague-Dawley rats were inoculated, within 36 hr of birth, with either of two strains of herpes simplex virus type 2. The effects of treatment for five days with either 5-iododeoxyuridine or cytosine arabinoside in near toxic doses were studied. Evaluation of treatment based on rate of survival, incidence of lesions, and isolation of virus from the central nervous system showed no appreciable difference between treated and untreated littermates. Drug-related effects of retardation of growth and defective development of the cerebellum and retina were found. The validity of therapy with either of these drugs in generalized herpetic infections is questioned because activity was minimal against the infecting agent even when the dosage of the drug was sufficient to produce serious defects in certain developing tissues.", "contents": "Experimental infection with herpes simplex virus type 2 in newborn rats: Effects of treatment with iododeoxyuridine and cytosine arabinoside. Sprague-Dawley rats were inoculated, within 36 hr of birth, with either of two strains of herpes simplex virus type 2. The effects of treatment for five days with either 5-iododeoxyuridine or cytosine arabinoside in near toxic doses were studied. Evaluation of treatment based on rate of survival, incidence of lesions, and isolation of virus from the central nervous system showed no appreciable difference between treated and untreated littermates. Drug-related effects of retardation of growth and defective development of the cerebellum and retina were found. The validity of therapy with either of these drugs in generalized herpetic infections is questioned because activity was minimal against the infecting agent even when the dosage of the drug was sufficient to produce serious defects in certain developing tissues."} {"id": "PMID:169312", "title": "Antiviral activity of adenine arabinoside and iododeoxyuridine in human fetal intestinal and tracheal organ cultures.", "content": "In vitro antiviral activities of two potentially clinically useful antiviral compounds, adenine arabinoside and iododeoxyuridine, were examined in human fetal intestinal and tracheal organ cultures infected with Herpesvirus hominis (types 1 and 2) or vaccinia virus. The two compounds were similarly active against the viruses in organ culture, and minimal inhibitory concentrations could be determined by titration of organ culture fluid harvests into tissue culture or directly in the organ cultures themselves. Minimal inhibitory concentrations were consistently lower in tracheal than in intestinal organ cultures and were consistently higher for H. hominis type 2 than for H. hominis type 1. Thus the organ cultures are promising systems in which to evaluate antiviral activity against those agents that replicate in vitro only in organ culture, and they may have particular application to the study of herpetic tracheitis and esophagitis.", "contents": "Antiviral activity of adenine arabinoside and iododeoxyuridine in human fetal intestinal and tracheal organ cultures. In vitro antiviral activities of two potentially clinically useful antiviral compounds, adenine arabinoside and iododeoxyuridine, were examined in human fetal intestinal and tracheal organ cultures infected with Herpesvirus hominis (types 1 and 2) or vaccinia virus. The two compounds were similarly active against the viruses in organ culture, and minimal inhibitory concentrations could be determined by titration of organ culture fluid harvests into tissue culture or directly in the organ cultures themselves. Minimal inhibitory concentrations were consistently lower in tracheal than in intestinal organ cultures and were consistently higher for H. hominis type 2 than for H. hominis type 1. Thus the organ cultures are promising systems in which to evaluate antiviral activity against those agents that replicate in vitro only in organ culture, and they may have particular application to the study of herpetic tracheitis and esophagitis."} {"id": "PMID:169313", "title": "Immunofluorescent staining for the measurement of antibodies to Herpesvirus hominis.", "content": "Frozen sections of Herpesvirus hominis-inoculated mouse brain provide excellent antigens for indirect immunofluorescent staining of antibodies to H. hominis in serum. Indirect immunofluorescent staining is a rapid, sensitive, and reproducible method for the measurement of antibodies to H. hominis. The method can be applied to the clinical and epidemiological studies of H. hominis infections.", "contents": "Immunofluorescent staining for the measurement of antibodies to Herpesvirus hominis. Frozen sections of Herpesvirus hominis-inoculated mouse brain provide excellent antigens for indirect immunofluorescent staining of antibodies to H. hominis in serum. Indirect immunofluorescent staining is a rapid, sensitive, and reproducible method for the measurement of antibodies to H. hominis. The method can be applied to the clinical and epidemiological studies of H. hominis infections."} {"id": "PMID:169317", "title": "Variations in hybridization of RNA from different mouse tissues and embryos to endogenous C-type virus DNA transcripts.", "content": "Several adult tissues, newborns, and embryos of uninfected BALB/c mice were analysed for RNA complementary to [3H]-DNA transcripts synthesized from an endogenous type-C virus of BALB/c 3T3. The technique of RNA:DNA hybridization was used and the extent of hybridization was measured by the use of a single-strand-specific nuclease (S-I), purified from Aspergillus oryzae. Virus-specific RNA was detected in all adult and embryonic tissues tested. However, the RNA extracted from tissues having higher proliferative activity, such as spleen, small intestine, uterus and embryos, hybridize the [3H]-DNA probe to a greater extent than the RNA from tissues with low proliferative activity, such as kidney and liver. These observations add further support to the view that the repression of the virus genome in normal cells is not complete, and suggest the existence of a correlation between a qualitative or quantitative change in the endogenous C-type virus genome transcription pattern and cell proliferation.", "contents": "Variations in hybridization of RNA from different mouse tissues and embryos to endogenous C-type virus DNA transcripts. Several adult tissues, newborns, and embryos of uninfected BALB/c mice were analysed for RNA complementary to [3H]-DNA transcripts synthesized from an endogenous type-C virus of BALB/c 3T3. The technique of RNA:DNA hybridization was used and the extent of hybridization was measured by the use of a single-strand-specific nuclease (S-I), purified from Aspergillus oryzae. Virus-specific RNA was detected in all adult and embryonic tissues tested. However, the RNA extracted from tissues having higher proliferative activity, such as spleen, small intestine, uterus and embryos, hybridize the [3H]-DNA probe to a greater extent than the RNA from tissues with low proliferative activity, such as kidney and liver. These observations add further support to the view that the repression of the virus genome in normal cells is not complete, and suggest the existence of a correlation between a qualitative or quantitative change in the endogenous C-type virus genome transcription pattern and cell proliferation."} {"id": "PMID:169318", "title": "Genetic susceptibility of chicken times quail hybrid embryos to avian RNA tumour viruses.", "content": "An attempt was made to hybridize the chicken (Gallus domesticus) male with Japanese quail (Coturnix coturnix japonica) female in order to study the genetic susceptibility of hybrid embryos to avian RNA tumour viruses of subgroups, A, B, D and E. In the hybrids the results supported the prevailing concept that susceptibility is dominant over resistance regardless of the dominant trait contributed by either parent. It was also observed that the Ie gene of the chicken was unable to suppress the 'quail-coded' susceptibility to subgroup E virus in the hybrid system, suggesting the lack of penetrance of the Ie gene. Despite the fact that some hybrids were resistant to viruses of subgroups B and D, they were susceptible to subgroup E virus, which was not expected on the basis of the concept that subgroup B-resistant cells cannot be E-susceptible. Also, the hybrids were susceptible to E virus regardless of gs antigen expression and presence of the Ie gene in the genome. This indicates that our earlier suggestion that the Ie gene is another expression of the gs antigen-determining gene is inconsistent.", "contents": "Genetic susceptibility of chicken times quail hybrid embryos to avian RNA tumour viruses. An attempt was made to hybridize the chicken (Gallus domesticus) male with Japanese quail (Coturnix coturnix japonica) female in order to study the genetic susceptibility of hybrid embryos to avian RNA tumour viruses of subgroups, A, B, D and E. In the hybrids the results supported the prevailing concept that susceptibility is dominant over resistance regardless of the dominant trait contributed by either parent. It was also observed that the Ie gene of the chicken was unable to suppress the 'quail-coded' susceptibility to subgroup E virus in the hybrid system, suggesting the lack of penetrance of the Ie gene. Despite the fact that some hybrids were resistant to viruses of subgroups B and D, they were susceptible to subgroup E virus, which was not expected on the basis of the concept that subgroup B-resistant cells cannot be E-susceptible. Also, the hybrids were susceptible to E virus regardless of gs antigen expression and presence of the Ie gene in the genome. This indicates that our earlier suggestion that the Ie gene is another expression of the gs antigen-determining gene is inconsistent."} {"id": "PMID:169319", "title": "Virus-specific proteins associated with the replication complex of poliovirus RNA.", "content": "The poliovirus replication complex was isolated and purified from infected HeLa S3 cells. Preparations with RNA-dependent RNA polymerase activity were concentrated 200- and 1000-fold with respect to the original virus and total protein content. The enzyme activity was found to be associated with the proteins NCVPI, 2, 3, 4, (5), 6 and VPl/NCVPx. The structural proteins VP2, 3 and 4 were not present. Addition of cycloheximide to infected cells resulted in a decrease in the in vitro polymerase activity and a loss in NCVPI content. Treatment of the infected cells with toloylsulphonyl-phenylalanine chloromethyl ketone (TPCK) and iodoacetamide (IAA) led to an inhibition of in vivo RNA synthesis. The 750 g supernatant fluids obtained from extracts of these cells were able to block RNA synthesis in vitro. Electrophoretic profiles of the respective protein compositions indicate that large virus precursor proteins are responsible for the inhibition of poliovirus RNA synthesis in vivo and in vitro.", "contents": "Virus-specific proteins associated with the replication complex of poliovirus RNA. The poliovirus replication complex was isolated and purified from infected HeLa S3 cells. Preparations with RNA-dependent RNA polymerase activity were concentrated 200- and 1000-fold with respect to the original virus and total protein content. The enzyme activity was found to be associated with the proteins NCVPI, 2, 3, 4, (5), 6 and VPl/NCVPx. The structural proteins VP2, 3 and 4 were not present. Addition of cycloheximide to infected cells resulted in a decrease in the in vitro polymerase activity and a loss in NCVPI content. Treatment of the infected cells with toloylsulphonyl-phenylalanine chloromethyl ketone (TPCK) and iodoacetamide (IAA) led to an inhibition of in vivo RNA synthesis. The 750 g supernatant fluids obtained from extracts of these cells were able to block RNA synthesis in vitro. Electrophoretic profiles of the respective protein compositions indicate that large virus precursor proteins are responsible for the inhibition of poliovirus RNA synthesis in vivo and in vitro."} {"id": "PMID:169325", "title": "Alcoholic neuropathy. An electron-microscopic study.", "content": "The sural nerves of 6 patients with different signs of alcoholic neuropathy were studied qualitatively and quantitatively by electron microscopy. Myelinated and unmyelinated fibres showed degenerative changes of the Wallerian type. Concomitant involvement of the myelin appears to be secondary to axonal lesions. Regenerative processes, although frequently observed, did not balance the destruction of fibres in the degenerative phase. Quantitative studies indicated a reduced number of myelinated fibres and decreased percentage of the area covered in cross-section by myelinated and unmyelinated axons. The histograms of myelinated fibres showed a shift to the left of the peak of large and small fibres and an increased number of small-sized fibres. Similarly the histograms of unmyelinated fibres showed a shift to the left and a bimodal distribution with an increased number of small-sized fibres. Imbalance in degenerative and regenerative processes seems to be the basis of the chronic partial denervation observed in the nerves of alcoholic patients in this study.", "contents": "Alcoholic neuropathy. An electron-microscopic study. The sural nerves of 6 patients with different signs of alcoholic neuropathy were studied qualitatively and quantitatively by electron microscopy. Myelinated and unmyelinated fibres showed degenerative changes of the Wallerian type. Concomitant involvement of the myelin appears to be secondary to axonal lesions. Regenerative processes, although frequently observed, did not balance the destruction of fibres in the degenerative phase. Quantitative studies indicated a reduced number of myelinated fibres and decreased percentage of the area covered in cross-section by myelinated and unmyelinated axons. The histograms of myelinated fibres showed a shift to the left of the peak of large and small fibres and an increased number of small-sized fibres. Similarly the histograms of unmyelinated fibres showed a shift to the left and a bimodal distribution with an increased number of small-sized fibres. Imbalance in degenerative and regenerative processes seems to be the basis of the chronic partial denervation observed in the nerves of alcoholic patients in this study."} {"id": "PMID:169326", "title": "Ultrastructural studies in human polymyositis.", "content": "Biopsy of muscle from 13 cases of human polymyositis permitted an ultrastructural study in which attention was directed to the cellular population of the inflammatory reaction. The constant feature was the presence of small and large lymphocytes, and cells of the latter type were frequently in intimate contact with the surface of the muscle fibres. Macrophages were seen both within and outside degenerating muscle fibres. Plasma cells were seen in 2 cases. Filaments bearing some resemblance to virus inclusions were seen in one case. The implications of the cellular reaction in human polymyositis are discussed and the literature of ultrastructural observations on the muscle in this disease is briefly reviewed.", "contents": "Ultrastructural studies in human polymyositis. Biopsy of muscle from 13 cases of human polymyositis permitted an ultrastructural study in which attention was directed to the cellular population of the inflammatory reaction. The constant feature was the presence of small and large lymphocytes, and cells of the latter type were frequently in intimate contact with the surface of the muscle fibres. Macrophages were seen both within and outside degenerating muscle fibres. Plasma cells were seen in 2 cases. Filaments bearing some resemblance to virus inclusions were seen in one case. The implications of the cellular reaction in human polymyositis are discussed and the literature of ultrastructural observations on the muscle in this disease is briefly reviewed."} {"id": "PMID:169327", "title": "Prognosis in adult polymyositis.", "content": "The effects of long-term corticosteroid treatment have been assessed in 20 patients with polymyositis. Cases were only accepted if a muscle biopsy showed the characteristic features of inflammation and muscle fibre degeneration. If the muscle disorder was only a minor feature of generalised collagen disease or there was evidence of coexisting neuropathy, the patients were excluded. Over a mean follow-up period of 5 years, 8 patients died and only 4 improved. These results have been compared with those in other series. An attempt has been made to correlate muscle biopsy findings with prognosis, and the reasons for the poor outcome are discussed.", "contents": "Prognosis in adult polymyositis. The effects of long-term corticosteroid treatment have been assessed in 20 patients with polymyositis. Cases were only accepted if a muscle biopsy showed the characteristic features of inflammation and muscle fibre degeneration. If the muscle disorder was only a minor feature of generalised collagen disease or there was evidence of coexisting neuropathy, the patients were excluded. Over a mean follow-up period of 5 years, 8 patients died and only 4 improved. These results have been compared with those in other series. An attempt has been made to correlate muscle biopsy findings with prognosis, and the reasons for the poor outcome are discussed."} {"id": "PMID:169328", "title": "Demonstration of enzymes related to myelinogenesis in established human brain cell cultures.", "content": "CNP, CGalT and PAPS-CST, enzymes involved in myelinogenesis were demonstrated in cultures derived from human brain. Little or no CNP activity could be found in cultures derived from non-neurogenic tissue. Transformation of brain cultures by PML-SV40 virus resulted in a 3 to 10-fold increase in the specific activity of CNP.", "contents": "Demonstration of enzymes related to myelinogenesis in established human brain cell cultures. CNP, CGalT and PAPS-CST, enzymes involved in myelinogenesis were demonstrated in cultures derived from human brain. Little or no CNP activity could be found in cultures derived from non-neurogenic tissue. Transformation of brain cultures by PML-SV40 virus resulted in a 3 to 10-fold increase in the specific activity of CNP."} {"id": "PMID:169329", "title": "Analysis of liver scanning in a general hospital.", "content": "The specificity and sensitivity of liver scanning in a general referral population of 125 patients was studied. All patients had a liver biopsy prior to the scan or not more than 10 days later. The results of this study were compared with one earlier and one ongoing study in the same laboratory. The differences in accuracy are mostly attributable to the difference in the populations studied. It is apparent that the multiple-view scintillation camera technique is not superior to the rectilinear two-view scans for studying the liver.", "contents": "Analysis of liver scanning in a general hospital. The specificity and sensitivity of liver scanning in a general referral population of 125 patients was studied. All patients had a liver biopsy prior to the scan or not more than 10 days later. The results of this study were compared with one earlier and one ongoing study in the same laboratory. The differences in accuracy are mostly attributable to the difference in the populations studied. It is apparent that the multiple-view scintillation camera technique is not superior to the rectilinear two-view scans for studying the liver."} {"id": "PMID:169330", "title": "Evaluation of soft-tissue calcifications in dermatomyositis with 99mTc-phosphate compounds: case report.", "content": "A whole-body scan with 99mTc-pyrophosphate and 85Sr-nitrate demonstrates extension of calcinosis in one case of dermatomyositis with cutaneous, subcutaneous, and muscular calcinosis. The authors suggest the potential use of 99mTc-phosphate compounds as an auxiliary instrument in the evaluation of dermatomyositis-polymyositis syndrome.", "contents": "Evaluation of soft-tissue calcifications in dermatomyositis with 99mTc-phosphate compounds: case report. A whole-body scan with 99mTc-pyrophosphate and 85Sr-nitrate demonstrates extension of calcinosis in one case of dermatomyositis with cutaneous, subcutaneous, and muscular calcinosis. The authors suggest the potential use of 99mTc-phosphate compounds as an auxiliary instrument in the evaluation of dermatomyositis-polymyositis syndrome."} {"id": "PMID:169331", "title": "Gallium uptake in benign tumor of liver: case report.", "content": "A case of positive tracer localization in a benign tumor of the liver on a 67Ga-citrate scan is reported. The authors were unable to find any previous reports of positive localization of gallium in this type of liver tumor.", "contents": "Gallium uptake in benign tumor of liver: case report. A case of positive tracer localization in a benign tumor of the liver on a 67Ga-citrate scan is reported. The authors were unable to find any previous reports of positive localization of gallium in this type of liver tumor."} {"id": "PMID:169333", "title": "Effects of dietary protein and calcium levels on renal glucose-6-phosphatase activity of intact and thyroparathyroidectomized rats.", "content": "In order to determine the relationship of parathyroid hormone and levels of dietary protein and calcium with the activity of renal glucose-6-phosphatase (G6Pase), effects of two levels of dietary protein, namely, 25 and 75%, on the enzyme activity were compared at three levels of dietary calcium, namely, 0.06, 0.63, and 1.83%, with the use of intact and thyroparathyroidectomized (TPTX) rats. In intact rats, 0.06% dietary calcium caused an increase in renal G6Pase activity in rats fed the high carbohydrate diet, and dietary calcium in excess (1.83%) caused the enzyme activity to decrease. Similar responses in the activity of renal G6Pase to the variation of dietary calcium levels were seen in rats fed the high protein diet, but significant differences were not obtained. In TPTX rats fed the high carbohydrate diet, the activity of renal G6Pase was significantly decreased compared with that of intact rats. When TPTX rats were fed the high protein diet, however, no significant decrease in the enzyme activity was observed. Free access to aqueous 0.1% CaC1(2) solution by TPTX rats tended to restore the activity of renal G6Pase and serum calcium concentrations depressed by thyroparathyroidectomy. In addition, a significant correlation was observed between the total activity of renal G6Pase and serum calcium concentrations. Hypothyroidism produced by oral administration of propylthiouracil (0.05% of diets) did not affect the enzyme activity in the kidneys of rats fed the high carbohydrate and the high protein diets. The results suggest that the activity of renal G6Pase of rats fed the high protein diet might be less susceptible both to dietary calcium levels and to parathyroid function than that of rats fed the high carbohydrate diet.", "contents": "Effects of dietary protein and calcium levels on renal glucose-6-phosphatase activity of intact and thyroparathyroidectomized rats. In order to determine the relationship of parathyroid hormone and levels of dietary protein and calcium with the activity of renal glucose-6-phosphatase (G6Pase), effects of two levels of dietary protein, namely, 25 and 75%, on the enzyme activity were compared at three levels of dietary calcium, namely, 0.06, 0.63, and 1.83%, with the use of intact and thyroparathyroidectomized (TPTX) rats. In intact rats, 0.06% dietary calcium caused an increase in renal G6Pase activity in rats fed the high carbohydrate diet, and dietary calcium in excess (1.83%) caused the enzyme activity to decrease. Similar responses in the activity of renal G6Pase to the variation of dietary calcium levels were seen in rats fed the high protein diet, but significant differences were not obtained. In TPTX rats fed the high carbohydrate diet, the activity of renal G6Pase was significantly decreased compared with that of intact rats. When TPTX rats were fed the high protein diet, however, no significant decrease in the enzyme activity was observed. Free access to aqueous 0.1% CaC1(2) solution by TPTX rats tended to restore the activity of renal G6Pase and serum calcium concentrations depressed by thyroparathyroidectomy. In addition, a significant correlation was observed between the total activity of renal G6Pase and serum calcium concentrations. Hypothyroidism produced by oral administration of propylthiouracil (0.05% of diets) did not affect the enzyme activity in the kidneys of rats fed the high carbohydrate and the high protein diets. The results suggest that the activity of renal G6Pase of rats fed the high protein diet might be less susceptible both to dietary calcium levels and to parathyroid function than that of rats fed the high carbohydrate diet."} {"id": "PMID:169336", "title": "Radiographic survey of perlite workers.", "content": "Chest roentgenograms of 240 perlite workers employed for 1 to 23 years in the industry, showed no evidence of pneumoconiosis associated with perlite exposures. One individual, found to have simple pneumoconiosis, and one found to have complicated pneumoconiosis, had formerly been diatomaceous earth workers. Since only 28 of the men had been in the industry over 15 years and only seven for 20 years or more, continued surveillance is essential to make sure that there are no effects with more prolonged exposures. Studies of pulmonary function of the individuals who have had relatively long exposures are needed to supplement radiographic evidence.", "contents": "Radiographic survey of perlite workers. Chest roentgenograms of 240 perlite workers employed for 1 to 23 years in the industry, showed no evidence of pneumoconiosis associated with perlite exposures. One individual, found to have simple pneumoconiosis, and one found to have complicated pneumoconiosis, had formerly been diatomaceous earth workers. Since only 28 of the men had been in the industry over 15 years and only seven for 20 years or more, continued surveillance is essential to make sure that there are no effects with more prolonged exposures. Studies of pulmonary function of the individuals who have had relatively long exposures are needed to supplement radiographic evidence."} {"id": "PMID:169338", "title": "Pulmonary sarcoidosis: A clinico-pathological study.", "content": "The light and electron microscopic changes in biopsy tissue from the lung of a 30-year-old housewife severeley incapacitated by diffuse pulmonary sarcoidosis with pulmonary hypertension are presented. The lung tissue was distorted by numerous granulomas in the interstitial tissues and within alveoli. Many pulmonary blood vessels including arteries were damaged by the granulomas. The ultrastructural features of the epithelioid cells were found to be distinctive and probably specific. The giant cells which accompanied the epithelioid cells contained two types of inclusion body: one appeared to be related to the Schaumann body but the nature and origin of the second type was not clear. Many of the granulomas were surrounded by avascular fibrous tissue which contained, in addition to mature fibroblasts, myofibroblasts and a primitive form of cell that appeared to be a fibroblast precursor. It was conjectured that the myofibroblasts, through their contractile powers, might increase the distortion of the lung architecture and thereby the patient's disability. The alveolar walls were thickened by a diffuse infiltrate of macrophages and epithelioid cells but there was no excess of collagen and elastic fibres. The evidence suggested that the epithelioid cells developed from macrophages. From the cellular nature of the diffuse infiltration of the alveolar walls and the absence of fibrosis it seemed that the disease was still at an early and active stage, a conclusion strengthened by the fact that treatment with corticosteroids led to marked and sustained clinical improvement.", "contents": "Pulmonary sarcoidosis: A clinico-pathological study. The light and electron microscopic changes in biopsy tissue from the lung of a 30-year-old housewife severeley incapacitated by diffuse pulmonary sarcoidosis with pulmonary hypertension are presented. The lung tissue was distorted by numerous granulomas in the interstitial tissues and within alveoli. Many pulmonary blood vessels including arteries were damaged by the granulomas. The ultrastructural features of the epithelioid cells were found to be distinctive and probably specific. The giant cells which accompanied the epithelioid cells contained two types of inclusion body: one appeared to be related to the Schaumann body but the nature and origin of the second type was not clear. Many of the granulomas were surrounded by avascular fibrous tissue which contained, in addition to mature fibroblasts, myofibroblasts and a primitive form of cell that appeared to be a fibroblast precursor. It was conjectured that the myofibroblasts, through their contractile powers, might increase the distortion of the lung architecture and thereby the patient's disability. The alveolar walls were thickened by a diffuse infiltrate of macrophages and epithelioid cells but there was no excess of collagen and elastic fibres. The evidence suggested that the epithelioid cells developed from macrophages. From the cellular nature of the diffuse infiltration of the alveolar walls and the absence of fibrosis it seemed that the disease was still at an early and active stage, a conclusion strengthened by the fact that treatment with corticosteroids led to marked and sustained clinical improvement."} {"id": "PMID:169339", "title": "Malignant chondroid syringoma of the thigh. Report of a case with electron microscopy of the tumour.", "content": "A case of malignant chondroid syringoma occurring in a 52-year-old female is reported. The tumour presented as a large, cystic lesion of the thigh. Local recurrence and secondary deposits in the inguinal region occurred at an early stage. The rarity of these malignant tumours and metastasising sweat gland tumours in general is emphasised.", "contents": "Malignant chondroid syringoma of the thigh. Report of a case with electron microscopy of the tumour. A case of malignant chondroid syringoma occurring in a 52-year-old female is reported. The tumour presented as a large, cystic lesion of the thigh. Local recurrence and secondary deposits in the inguinal region occurred at an early stage. The rarity of these malignant tumours and metastasising sweat gland tumours in general is emphasised."} {"id": "PMID:169340", "title": "Hepatotoxicity of chemotherapy following nephrectomy and radiation therapy for right-sided Wilms tumor.", "content": "Two children developed hepatotoxicity during treatment for right-sided Wilms Tumor. Treatment consisted of nephrectomy, irradiation, and chemotherapy with actinomycin D and vincristine. Hepatic enlargement, thrombocytopenia, and abnormalities in liver function and seen on the liver scan occurred at the time of the course of chemotherapy administered 20 days after completion of irradiation. These abnormalities disappeared when treatment was temporarily suspended. Vincristine and actinomycin D were subsequently reintroduced without evidence of hepatotoxicity. Actinomycin D after irradiation for right-sided Wilms tumor may produce severe liver toxicity.", "contents": "Hepatotoxicity of chemotherapy following nephrectomy and radiation therapy for right-sided Wilms tumor. Two children developed hepatotoxicity during treatment for right-sided Wilms Tumor. Treatment consisted of nephrectomy, irradiation, and chemotherapy with actinomycin D and vincristine. Hepatic enlargement, thrombocytopenia, and abnormalities in liver function and seen on the liver scan occurred at the time of the course of chemotherapy administered 20 days after completion of irradiation. These abnormalities disappeared when treatment was temporarily suspended. Vincristine and actinomycin D were subsequently reintroduced without evidence of hepatotoxicity. Actinomycin D after irradiation for right-sided Wilms tumor may produce severe liver toxicity."} {"id": "PMID:169341", "title": "Adriamycin cardiotoxicity in a child with Wilms tumor. Report of a case and review of the literature.", "content": "A case of adriamycin-induced carciomyopathy in a 5 3/4-year-old girl with metastatic Wilms tumor is reported. Potentiation of the adriamycin cardiotoxicity by irradiation to the heart is proposed; the clinical and pathologic findings are discussed.", "contents": "Adriamycin cardiotoxicity in a child with Wilms tumor. Report of a case and review of the literature. A case of adriamycin-induced carciomyopathy in a 5 3/4-year-old girl with metastatic Wilms tumor is reported. Potentiation of the adriamycin cardiotoxicity by irradiation to the heart is proposed; the clinical and pathologic findings are discussed."} {"id": "PMID:169345", "title": "Interactions of morphine, adenosine, adenosine triphosphate and phosphodiesterase inhibitors on the field-stimulated guinea-pig ileum.", "content": "Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index to the relative potency of various narcotic analgesics. This property suggests that this preparation might be used as a model in attempts to elucidate the mechanism(s) by which morphine induces analgesia in the central nervous system. Since it has been demonstrated that some adenosine derivative may function as an endogenous inhibitory transmitter in the gut, the effects of adenosine, adenosine triphosphate (ATP) and morphine on the ileum were further characterized and compared. Morphine, adenosine and ATP produce a substantial inhibition of the isometric contractions induced by transmural field stimulation. The inhibition produced by each is antagonized by 2.5 times 10(-7) M tolazoline whereas that produced by ATP is potentiated by 4 times 10(-7) M 5-hydroxytryptamine. The inhibitory effects of morphine and ATP can also be markedly potentiated by two of the several phosphodiesterase inhibitors tested, Ro 20-1724 and dipyridamole. In addition, pretreatment of the ileum with either adenosine, ATP or morphine can produce a significant potentiation of the inhibitory effects of norepinephrine. The above suggests that cyclic adenosine 3',5'-monophosphate may play a role in mediating some of the inhibitory effects produced by exogenous adenosine, ATP and morphine. In addition, the similarities between the effects produced by these substances indicates that the biochemical pathways responsible for mediating the effects of each may share some common elements.", "contents": "Interactions of morphine, adenosine, adenosine triphosphate and phosphodiesterase inhibitors on the field-stimulated guinea-pig ileum. Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index to the relative potency of various narcotic analgesics. This property suggests that this preparation might be used as a model in attempts to elucidate the mechanism(s) by which morphine induces analgesia in the central nervous system. Since it has been demonstrated that some adenosine derivative may function as an endogenous inhibitory transmitter in the gut, the effects of adenosine, adenosine triphosphate (ATP) and morphine on the ileum were further characterized and compared. Morphine, adenosine and ATP produce a substantial inhibition of the isometric contractions induced by transmural field stimulation. The inhibition produced by each is antagonized by 2.5 times 10(-7) M tolazoline whereas that produced by ATP is potentiated by 4 times 10(-7) M 5-hydroxytryptamine. The inhibitory effects of morphine and ATP can also be markedly potentiated by two of the several phosphodiesterase inhibitors tested, Ro 20-1724 and dipyridamole. In addition, pretreatment of the ileum with either adenosine, ATP or morphine can produce a significant potentiation of the inhibitory effects of norepinephrine. The above suggests that cyclic adenosine 3',5'-monophosphate may play a role in mediating some of the inhibitory effects produced by exogenous adenosine, ATP and morphine. In addition, the similarities between the effects produced by these substances indicates that the biochemical pathways responsible for mediating the effects of each may share some common elements."} {"id": "PMID:169346", "title": "Effect of chlorpropamide on renal response to parathyroid hormone in normal subjects and in patients with hypoparathyroidism and pseudohypoparathyroidism.", "content": "Chlorpropamide inhibited by 35 to 65% the increase in the urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) following a large dose (250 U) of parathyroid hormone (PTH) in normal subjects and patients with hypoparathyroidism and pseudohypoparathyroidism. By contrast, in normal subjects, the response of urinary cyclic AMP excretion to smaller amounts of PTH (15 and 30 U) was not decreased by chlorpropamide. Chlorpropamide did not decrease the phosphaturic response to any dose of PTH. The probable explanation for the discrepant effects of chlorpropamide on urinary cyclic AMP and phosphate excretions is that phosphaturia results from a minimal elevation of cyclic AMP and that chlorpropamide does not decrease cyclic AMP production to such a low level. Chlorpropamide decreased the accumulation of renal cyclic AMP in response to PTH in the parathyroidectomized rat, suggesting that this may be the mechanism of action for this drug in decreasing the urinary excretion of cyclic AMP in response to PTH in man. Tolazamide, another sulfonylurea, did not inhibit the elevation of urinary cyclic AMP excretion after PTH. Therefore, the sulfonylurea part of the molecule is probably not involved in the inhibition produced by chlorpropamide.", "contents": "Effect of chlorpropamide on renal response to parathyroid hormone in normal subjects and in patients with hypoparathyroidism and pseudohypoparathyroidism. Chlorpropamide inhibited by 35 to 65% the increase in the urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) following a large dose (250 U) of parathyroid hormone (PTH) in normal subjects and patients with hypoparathyroidism and pseudohypoparathyroidism. By contrast, in normal subjects, the response of urinary cyclic AMP excretion to smaller amounts of PTH (15 and 30 U) was not decreased by chlorpropamide. Chlorpropamide did not decrease the phosphaturic response to any dose of PTH. The probable explanation for the discrepant effects of chlorpropamide on urinary cyclic AMP and phosphate excretions is that phosphaturia results from a minimal elevation of cyclic AMP and that chlorpropamide does not decrease cyclic AMP production to such a low level. Chlorpropamide decreased the accumulation of renal cyclic AMP in response to PTH in the parathyroidectomized rat, suggesting that this may be the mechanism of action for this drug in decreasing the urinary excretion of cyclic AMP in response to PTH in man. Tolazamide, another sulfonylurea, did not inhibit the elevation of urinary cyclic AMP excretion after PTH. Therefore, the sulfonylurea part of the molecule is probably not involved in the inhibition produced by chlorpropamide."} {"id": "PMID:169348", "title": "Protein kinases activated by cAMP in the genital tract of spayed mice treated with oestradiol-17beta.", "content": "The cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37), has been studied in the vaginal epithelium, vaginal stroma, endometrium, and whole uterus of spayed mice treated with oestradiol-17 beta, and in the vaginal epithelium and uterus of spayed mice. Two protein kinase isoenzymes (PK I and PK II) were found in whole uterus, endometrium, and vaginal stroma. Vaginal epithelium contained only one isoenzyme (PK II). Oestradiol treatment increased PK I relative to PK II in the uterus. The isoenzyme pattern in the vaginal epithelium was unaltered after such treatment. The total protein kinase activity was 70% higher in uterine extracts (cytosol) than in extracts from vaginal epithelium. Oestradiol treatment did not influence the total protein kinase activity in either tissue.", "contents": "Protein kinases activated by cAMP in the genital tract of spayed mice treated with oestradiol-17beta. The cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37), has been studied in the vaginal epithelium, vaginal stroma, endometrium, and whole uterus of spayed mice treated with oestradiol-17 beta, and in the vaginal epithelium and uterus of spayed mice. Two protein kinase isoenzymes (PK I and PK II) were found in whole uterus, endometrium, and vaginal stroma. Vaginal epithelium contained only one isoenzyme (PK II). Oestradiol treatment increased PK I relative to PK II in the uterus. The isoenzyme pattern in the vaginal epithelium was unaltered after such treatment. The total protein kinase activity was 70% higher in uterine extracts (cytosol) than in extracts from vaginal epithelium. Oestradiol treatment did not influence the total protein kinase activity in either tissue."} {"id": "PMID:169349", "title": "Regulation of seminiferous tubular function by FSH and androgen.", "content": "Seminiferous tubules contain a cytoplasmic androgen receptor similar to the receptors in the epididymis and ventral prostate. The presence of a cytoplasmic receptor indicates that androgens maintain spermatogenesis by a direct action on certain types of cells within the seminiferous tubule. The Sertoli cell appears to be one of the cell types containing androgen receptors and the receptor might also be present in spermatogonia, primary spermatocytes, or peritubular cells. The Sertoli cell is stimulated by FSH to produce an androgen-binding protein which may serve to increase the accumulation of androgen in the seminiferous epithelium and make it available for binding by intracellular androgen receptors. This may be a way in which FSH enhances the action of androgen on spermatogenesis. Androgens act on the Sertoli cell to increase its response to FSH. This action of androgens on the Sertoli cell results in increased production of androgen-binding protein and may enhance the production of other substances which exert trophic effects on spermatogenesis.", "contents": "Regulation of seminiferous tubular function by FSH and androgen. Seminiferous tubules contain a cytoplasmic androgen receptor similar to the receptors in the epididymis and ventral prostate. The presence of a cytoplasmic receptor indicates that androgens maintain spermatogenesis by a direct action on certain types of cells within the seminiferous tubule. The Sertoli cell appears to be one of the cell types containing androgen receptors and the receptor might also be present in spermatogonia, primary spermatocytes, or peritubular cells. The Sertoli cell is stimulated by FSH to produce an androgen-binding protein which may serve to increase the accumulation of androgen in the seminiferous epithelium and make it available for binding by intracellular androgen receptors. This may be a way in which FSH enhances the action of androgen on spermatogenesis. Androgens act on the Sertoli cell to increase its response to FSH. This action of androgens on the Sertoli cell results in increased production of androgen-binding protein and may enhance the production of other substances which exert trophic effects on spermatogenesis."} {"id": "PMID:169351", "title": "Synthesis and cell culture studies on the antiviral activity of 5-mercaptomethyl-2'-deoxyuridine.", "content": "Treatment of 5-mercaptomethyluracil (I) with trimethylsilyl chloride in the presence of triethylamine gave 2,4,5-tris-(trimethylsilyl)-5-mercaptomethyluracil (II) which, upon coupling with 2-deoxy-3,5-di-O-(p-toluoyl)-D-erythro-pentofuranosyl chloride, furnished as anomeric mixture of fully substituted 2'-deoxy ribonucleosides. The nucleoside with beta configuration (III) was predominantly formed and was isolated as a crystalline solid. The free nucleoside IV was obtained by removal of blocking groups by sodium methoxide catalyzed deacylation, deionization under reducing atmosphere, and chromatography on neutral alumina. IV is oxidized to the corresponding disulfide V in solution in the absence of thiols. IV was found to be markedly inhibitory against the herpes virus of infectious bovine rhinotracheitis (IBR). Against this virus, IV was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside when added 18 hr before virus infection.", "contents": "Synthesis and cell culture studies on the antiviral activity of 5-mercaptomethyl-2'-deoxyuridine. Treatment of 5-mercaptomethyluracil (I) with trimethylsilyl chloride in the presence of triethylamine gave 2,4,5-tris-(trimethylsilyl)-5-mercaptomethyluracil (II) which, upon coupling with 2-deoxy-3,5-di-O-(p-toluoyl)-D-erythro-pentofuranosyl chloride, furnished as anomeric mixture of fully substituted 2'-deoxy ribonucleosides. The nucleoside with beta configuration (III) was predominantly formed and was isolated as a crystalline solid. The free nucleoside IV was obtained by removal of blocking groups by sodium methoxide catalyzed deacylation, deionization under reducing atmosphere, and chromatography on neutral alumina. IV is oxidized to the corresponding disulfide V in solution in the absence of thiols. IV was found to be markedly inhibitory against the herpes virus of infectious bovine rhinotracheitis (IBR). Against this virus, IV was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside when added 18 hr before virus infection."} {"id": "PMID:169352", "title": "Flavonoids. 8. Synthesis and antifertility and estrogen receptor binding activities of coumarins and delta3-isoflavenes.", "content": "A series of coumarins and delta3-isoflavenes was prepared. Although antifertility activity was shown by all of these compounds, the required dosage in mice varied from 13.5 mug/kg/day to 50 mg/kg/day. The most potent compounds were the 2-methyl-4-ethylisoflavenes, two of which (2a and 2b) were about equipotent with DES on a molar basis. They were followed by the 2,2-dimethylisoflavenes, the 2-unsubstituted isoflavene, and the coumarins. The most active compounds possessed an acetoxy group at C-7 and an oxygen function at C-4'. Presence of fluorine at C-4' or diethylaminoethoxy at C-M decreased the antifertility activity. The uterotropic activity followed the same trends as the antifertility activity with some evidence for the separation of the two effects in the 2,2-dimethylisoflavene series. Based on a limited study it appears that two phenolic hydroxyl groups are required for the presence of good estrogen receptor binding activity. An apparent lack of correlation between the estrogen binding activity and uterotropic or antifertility effects is probably explained by in vivo metabolism.", "contents": "Flavonoids. 8. Synthesis and antifertility and estrogen receptor binding activities of coumarins and delta3-isoflavenes. A series of coumarins and delta3-isoflavenes was prepared. Although antifertility activity was shown by all of these compounds, the required dosage in mice varied from 13.5 mug/kg/day to 50 mg/kg/day. The most potent compounds were the 2-methyl-4-ethylisoflavenes, two of which (2a and 2b) were about equipotent with DES on a molar basis. They were followed by the 2,2-dimethylisoflavenes, the 2-unsubstituted isoflavene, and the coumarins. The most active compounds possessed an acetoxy group at C-7 and an oxygen function at C-4'. Presence of fluorine at C-4' or diethylaminoethoxy at C-M decreased the antifertility activity. The uterotropic activity followed the same trends as the antifertility activity with some evidence for the separation of the two effects in the 2,2-dimethylisoflavene series. Based on a limited study it appears that two phenolic hydroxyl groups are required for the presence of good estrogen receptor binding activity. An apparent lack of correlation between the estrogen binding activity and uterotropic or antifertility effects is probably explained by in vivo metabolism."} {"id": "PMID:169353", "title": "Uptake in vitro of nucleic acid precursors and nucleic acids by Zajdela ascitic hepatoma cells.", "content": "Zajdela ascitic hepatoma cells are shown to take up pyrimidine bases at much lower rates than obtained in slices from normal rat liver. The rates of uptake of adenine and uridine by the Zajdela cells are, however, as high as in the slices. Like the slices, again, the Zajdela cells take up E. coli RNA and DNA at very low rates but, unlike the slices, thses cells degrade rapidly the RNA taken up. The Zajdela cells resemble parenchymal cell suspensions derived from normal rat liver in regard to the uptake of pyrimidine bases and the ability to degrade heterologous RNA.", "contents": "Uptake in vitro of nucleic acid precursors and nucleic acids by Zajdela ascitic hepatoma cells. Zajdela ascitic hepatoma cells are shown to take up pyrimidine bases at much lower rates than obtained in slices from normal rat liver. The rates of uptake of adenine and uridine by the Zajdela cells are, however, as high as in the slices. Like the slices, again, the Zajdela cells take up E. coli RNA and DNA at very low rates but, unlike the slices, thses cells degrade rapidly the RNA taken up. The Zajdela cells resemble parenchymal cell suspensions derived from normal rat liver in regard to the uptake of pyrimidine bases and the ability to degrade heterologous RNA."} {"id": "PMID:169357", "title": "Quantum chemical study of relative reactivities of a series of amines and nitriles: relevance to prebiotic chemistry.", "content": "Using the Iterative Extended Hucken Theory (IEHT) calculations of the elctron distribution and orbital energies of a series of thirteen amines, nitriles and amino-nitriles relevant to prebiotic and cosmo-chemistry have been carried out. Ground state properties such as the energy and nature of the highest occupied (HOMO) and lowest empty (LEMO) molecular orbitals, net atomic charges and number of non-bonding electrons have been identified as criteria for correlating the relative nucleophilicity of amine and nitrile nitrogens and the electrophilicity of nitrile and other unsaturated carbon atoms. The results of such correlations can be partially verified by known chemical behavior of these compounds and are used to predict and understand their role in prebiotic organic synthesis.", "contents": "Quantum chemical study of relative reactivities of a series of amines and nitriles: relevance to prebiotic chemistry. Using the Iterative Extended Hucken Theory (IEHT) calculations of the elctron distribution and orbital energies of a series of thirteen amines, nitriles and amino-nitriles relevant to prebiotic and cosmo-chemistry have been carried out. Ground state properties such as the energy and nature of the highest occupied (HOMO) and lowest empty (LEMO) molecular orbitals, net atomic charges and number of non-bonding electrons have been identified as criteria for correlating the relative nucleophilicity of amine and nitrile nitrogens and the electrophilicity of nitrile and other unsaturated carbon atoms. The results of such correlations can be partially verified by known chemical behavior of these compounds and are used to predict and understand their role in prebiotic organic synthesis."} {"id": "PMID:169358", "title": "Study of double and triple simultaneous substitutions of amino acids in cytochromes C.", "content": "A statistical analysis aimed at obtaining some informations on a possible correlation between simultaneous amino acid substitutions is proposed. This method is applied to a set of cytochrome C, at the level of tandem and triple substitutions separated along the peptide chain by 1 to 15 peptide bonds. Monte-Carlo simulations are performed and the results are compared. We find a significant occurrence of three adjacent amino acid substitutions in which the first replacement requires a two nucleotide substitution. A possible explanation of this fact is proposed on the basis of covarions.", "contents": "Study of double and triple simultaneous substitutions of amino acids in cytochromes C. A statistical analysis aimed at obtaining some informations on a possible correlation between simultaneous amino acid substitutions is proposed. This method is applied to a set of cytochrome C, at the level of tandem and triple substitutions separated along the peptide chain by 1 to 15 peptide bonds. Monte-Carlo simulations are performed and the results are compared. We find a significant occurrence of three adjacent amino acid substitutions in which the first replacement requires a two nucleotide substitution. A possible explanation of this fact is proposed on the basis of covarions."} {"id": "PMID:169359", "title": "Evaluation of antitumor activity of Bordetella pertussis in two murine tumor models.", "content": "The antitumor activity of three preparations of killed Bordetella pertussis (Bp) (Eli Lilly crude and fluid pertussis vaccines and Parke-Davis pertussis vaccine) was studied in the B16 melanoma and CaD2 mammary adenocarcinoma models. In these tumor systems; Bp had weak and variable tumor inhibitory activity and did not augment tumor rejection immunity. The intratumor injection of Bp did not affect the growth of the B16 tumor but significantly inhibited the growth of the CaD2 tumor. However, the established tumor did not regress. Admixture of Bp with B16 cells before inoculation inhibited tumor growth and prolonged survival of inoculated mice. Admixture of Bp with CaD2 cells completely suppressed tumor cell growth in 60% of inoculated mice. Intratumor injection of CaD2 with Bp combined with surgery provided no protection against subsequent development of metastases.", "contents": "Evaluation of antitumor activity of Bordetella pertussis in two murine tumor models. The antitumor activity of three preparations of killed Bordetella pertussis (Bp) (Eli Lilly crude and fluid pertussis vaccines and Parke-Davis pertussis vaccine) was studied in the B16 melanoma and CaD2 mammary adenocarcinoma models. In these tumor systems; Bp had weak and variable tumor inhibitory activity and did not augment tumor rejection immunity. The intratumor injection of Bp did not affect the growth of the B16 tumor but significantly inhibited the growth of the CaD2 tumor. However, the established tumor did not regress. Admixture of Bp with B16 cells before inoculation inhibited tumor growth and prolonged survival of inoculated mice. Admixture of Bp with CaD2 cells completely suppressed tumor cell growth in 60% of inoculated mice. Intratumor injection of CaD2 with Bp combined with surgery provided no protection against subsequent development of metastases."} {"id": "PMID:169360", "title": "Tumor induction by carcinogenic agents in aquarium fish.", "content": "The effects of nine carcinogens on 1,220 guppies [Poecilea reticulata (Lebistes reticulatus)] and 40 zebra fish (Danio rerio) were studied. Multiple exposure techniques included skin application, im and ip injections, feeding, implantation in pellets, and dissolving of the compound in the aquarium water. 7-12-Dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzidine produced no tumors in the fish. N-2-Fluorenylacetamide, omicron-aminoazotoluene, 4-dimethylaminoazobenzene, diethylnitrosamine, and dimethylnitrosamine induced tumors in the livers of some of the fish. These neoplasms included cholangiomas, hepatoadenomas, cholangiocarcinomas, and hepatocellular cancers. Nitrosomorpholine caused not only hepatic tumors in guppies and zebra fish but also intestinal adenocarcinomas and poorly differentiated connective-tissue lesions in the abdominal cavities of zebra fish. Experimental induction of tumors in aquarium fish offers wide possibilities for comparative cancer research. Fish are a suitable model for the testing of compounds for carcinogenic activity and for the screening of environmental carcinogens.", "contents": "Tumor induction by carcinogenic agents in aquarium fish. The effects of nine carcinogens on 1,220 guppies [Poecilea reticulata (Lebistes reticulatus)] and 40 zebra fish (Danio rerio) were studied. Multiple exposure techniques included skin application, im and ip injections, feeding, implantation in pellets, and dissolving of the compound in the aquarium water. 7-12-Dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzidine produced no tumors in the fish. N-2-Fluorenylacetamide, omicron-aminoazotoluene, 4-dimethylaminoazobenzene, diethylnitrosamine, and dimethylnitrosamine induced tumors in the livers of some of the fish. These neoplasms included cholangiomas, hepatoadenomas, cholangiocarcinomas, and hepatocellular cancers. Nitrosomorpholine caused not only hepatic tumors in guppies and zebra fish but also intestinal adenocarcinomas and poorly differentiated connective-tissue lesions in the abdominal cavities of zebra fish. Experimental induction of tumors in aquarium fish offers wide possibilities for comparative cancer research. Fish are a suitable model for the testing of compounds for carcinogenic activity and for the screening of environmental carcinogens."} {"id": "PMID:169361", "title": "Response of microbodies in Morris hepatoma 9618A to clofibrate.", "content": "Regulation of the formation of microbodies in Morris hepatoma 9618A was studied by examination of the response of the organelles to clofibrate. The fine structures of microbodies in the hepatoma cells closely resembled those in hepatocytes of normal adult rats. In clofibrate-treated rats, the tumor cells showed a slight increase in the size of microbodies and in catalase activity; however, the tumor microbodies did not increase in number. In contrast, in adult clofibrate-treated rats and rats on the day of birth whose mothers received clofibrate during the gestation period, the hepatocytes showed microbodies that were greater in both number and size, and the catalase activity in the liver was definitely elevated.", "contents": "Response of microbodies in Morris hepatoma 9618A to clofibrate. Regulation of the formation of microbodies in Morris hepatoma 9618A was studied by examination of the response of the organelles to clofibrate. The fine structures of microbodies in the hepatoma cells closely resembled those in hepatocytes of normal adult rats. In clofibrate-treated rats, the tumor cells showed a slight increase in the size of microbodies and in catalase activity; however, the tumor microbodies did not increase in number. In contrast, in adult clofibrate-treated rats and rats on the day of birth whose mothers received clofibrate during the gestation period, the hepatocytes showed microbodies that were greater in both number and size, and the catalase activity in the liver was definitely elevated."} {"id": "PMID:169362", "title": "Zinc intake, neoplastic DNA synthesis, and chemical carcinogenesis in rats and mice.", "content": "DNA synthesis in a transplanted hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was significantly reduced (P less than 0.01) in rats maintained on diets low (0.4 mug/g) or high (greater than or equal to 500 mug/g) in zinc when compared with control animals given 60 mug zinc/g. 3-Methylcholanthrene-induced carcinogenesis was considerably lowered in mice receiving the same low or high zinc diets during the induction periods.", "contents": "Zinc intake, neoplastic DNA synthesis, and chemical carcinogenesis in rats and mice. DNA synthesis in a transplanted hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was significantly reduced (P less than 0.01) in rats maintained on diets low (0.4 mug/g) or high (greater than or equal to 500 mug/g) in zinc when compared with control animals given 60 mug zinc/g. 3-Methylcholanthrene-induced carcinogenesis was considerably lowered in mice receiving the same low or high zinc diets during the induction periods."} {"id": "PMID:169363", "title": "C-Type virus particles in a cell line from a lymphosarcoma of a nude mouse.", "content": "C-type virus particles were observed by electron microscopy in cultures of a cell line (NML-1) derived from a lymphosarcoma that arose spontaneously in a nude NIH outbred mouse. The presence of such particles indicated that human tumors heterotransplanted in nude mice might become contaminated with murine oncornaviruses.", "contents": "C-Type virus particles in a cell line from a lymphosarcoma of a nude mouse. C-type virus particles were observed by electron microscopy in cultures of a cell line (NML-1) derived from a lymphosarcoma that arose spontaneously in a nude NIH outbred mouse. The presence of such particles indicated that human tumors heterotransplanted in nude mice might become contaminated with murine oncornaviruses."} {"id": "PMID:169364", "title": "Oncogenesis by Marek's disease herpesvirus in chickens lacking expression of endogenous (gs, chick helper factor, Rous-associated virus-O) and exogenous avian RNA tumor viruses.", "content": "Chickens free of exogenous avian leukosis virus (ALV) infection, replicating endogenous ALV (Rous-associated virus-O), gs antigen, and chick helper factor were fully susceptible to induction of Marek's disease (MD) by ALV-free MD viruses. Dual infection with Rous-associated virus-2 and MD virus did not significantly alter the character of the MD lesions. Thus exogenous ALV infection was not requisite for MD virus-induced oncogenesis. Although participation of endogenous RNA tumor virus genes in MD lesion induction could not be excluded, expression of such genes in MD tumors as gs antigen was not established.", "contents": "Oncogenesis by Marek's disease herpesvirus in chickens lacking expression of endogenous (gs, chick helper factor, Rous-associated virus-O) and exogenous avian RNA tumor viruses. Chickens free of exogenous avian leukosis virus (ALV) infection, replicating endogenous ALV (Rous-associated virus-O), gs antigen, and chick helper factor were fully susceptible to induction of Marek's disease (MD) by ALV-free MD viruses. Dual infection with Rous-associated virus-2 and MD virus did not significantly alter the character of the MD lesions. Thus exogenous ALV infection was not requisite for MD virus-induced oncogenesis. Although participation of endogenous RNA tumor virus genes in MD lesion induction could not be excluded, expression of such genes in MD tumors as gs antigen was not established."} {"id": "PMID:169365", "title": "Antibodies to Herpes simplex virus in Jewish women with cervical cancer and in healthy Jewish women of Israel.", "content": "Herpes simplex virus (HSV) antibody titers were examined in sera from 39 Jewish women with squamous cell carcinoma of the uterine cervix (CaCx) and in sera from controls matched by age and country of origin. Highly significant differences were found between the cases and controls for both HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Compared to findings in other demographic areas, the geometric mean titer (GMT) of HSV-1 among the CaCx cases were considerably higher, whereas the GMT for HSV-2 was in the same range. The percentage of HSV-2-positive patients, as defined by the HSV-2/HSV-1 antibody titer ratio was low compared to that found in other demographic areas; this was presumably due to the high incidence of HSV-1 infection in the population. The HSV-1 and HSV-2 infection rate in the Israeli Jewish female population was estimated by antibody titers for 94 healthy subjects. The GMT of HSV-1 was considerably higher, whereas the GMT of HSV-2 was lower, than those reported elsewhere. The association found previously between HSV-2 and CaCx remained true for Jewish women. Their low incidence of CaCx, which did not seem to result from lower susceptibility, might be explained by the low incidence of HSV-2 infection.", "contents": "Antibodies to Herpes simplex virus in Jewish women with cervical cancer and in healthy Jewish women of Israel. Herpes simplex virus (HSV) antibody titers were examined in sera from 39 Jewish women with squamous cell carcinoma of the uterine cervix (CaCx) and in sera from controls matched by age and country of origin. Highly significant differences were found between the cases and controls for both HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Compared to findings in other demographic areas, the geometric mean titer (GMT) of HSV-1 among the CaCx cases were considerably higher, whereas the GMT for HSV-2 was in the same range. The percentage of HSV-2-positive patients, as defined by the HSV-2/HSV-1 antibody titer ratio was low compared to that found in other demographic areas; this was presumably due to the high incidence of HSV-1 infection in the population. The HSV-1 and HSV-2 infection rate in the Israeli Jewish female population was estimated by antibody titers for 94 healthy subjects. The GMT of HSV-1 was considerably higher, whereas the GMT of HSV-2 was lower, than those reported elsewhere. The association found previously between HSV-2 and CaCx remained true for Jewish women. Their low incidence of CaCx, which did not seem to result from lower susceptibility, might be explained by the low incidence of HSV-2 infection."} {"id": "PMID:169366", "title": "Aging changes in CD-1 HaM/ICR mice reared under standard laboratory conditions.", "content": "Three hundred CD-1 HaM/ICR mice were observed for 2 years, and useful necropsies were done on 99 males and 102 females. Mortality was 50% at 16 months in the males and 18 months in the females. Among mice that came to autopsy, total tumor incidence was 54% for males and 75% for females, with most neoplasms occurring after 18 months. Adenomas or adenocarcinomas of the lung were the most frequent, followed by lymphoreticular tumors, vascular tumors, hepatomas, subcutaneous fibrosarcomas, and adenocarcinomas of the mammary glands. Some degree of amyloidosis was seen in half the mice of both sexes, beginning at 8 months in males and 12 months in females. Variability in tumor incidence among small groups if mice emphasized the need for adequate samples.", "contents": "Aging changes in CD-1 HaM/ICR mice reared under standard laboratory conditions. Three hundred CD-1 HaM/ICR mice were observed for 2 years, and useful necropsies were done on 99 males and 102 females. Mortality was 50% at 16 months in the males and 18 months in the females. Among mice that came to autopsy, total tumor incidence was 54% for males and 75% for females, with most neoplasms occurring after 18 months. Adenomas or adenocarcinomas of the lung were the most frequent, followed by lymphoreticular tumors, vascular tumors, hepatomas, subcutaneous fibrosarcomas, and adenocarcinomas of the mammary glands. Some degree of amyloidosis was seen in half the mice of both sexes, beginning at 8 months in males and 12 months in females. Variability in tumor incidence among small groups if mice emphasized the need for adequate samples."} {"id": "PMID:169367", "title": "Extraction of tumor-specific antigen from cells and plasma membranes of line-10 hepatoma.", "content": "Tumor-specific antigen was extracted with 3 M KCl from line-10 guinea pig hepatoma cells. The yield of antigenic activity, estimated by production of delayed cutaneous hypersensitivity reactions in line-10 immune guinea pigs, was 10-30% of the antigen present in intact cells. By ultracentrifugation criteria, the extracted antigen was soluble. Gel filtration, ion exchange chromatography, and salting-out studies showed that the antigen was heterogeneous in size and net charge. The possibility that 3 M KCl extracted a homogeneous population of molecules associating into polymers of various sizes at low ionic strength was ruled out by heterogeneity on Sephadex G-200 chromatography at high ionic strength. After osmotic lysis of sucrose-loaded line-10 cells, whole plasma membranes or large membrane fragments were obtained in a yield of about 20%. The isolation procedure did not cause detectable loss of membrane antigenic activity. The membranes had 33 skin test U/mg membrane protein, compared to the intact cell value of 1.7 skin test U/mg cell protein. Extracts of plasma membranes had 10-20% of the antigenic activity of the starting membrane material. In contrast to the wide variety of proteins liberated from intact cells, much of the protein extracted from the membranes was in the molecular weight range above 250,000.", "contents": "Extraction of tumor-specific antigen from cells and plasma membranes of line-10 hepatoma. Tumor-specific antigen was extracted with 3 M KCl from line-10 guinea pig hepatoma cells. The yield of antigenic activity, estimated by production of delayed cutaneous hypersensitivity reactions in line-10 immune guinea pigs, was 10-30% of the antigen present in intact cells. By ultracentrifugation criteria, the extracted antigen was soluble. Gel filtration, ion exchange chromatography, and salting-out studies showed that the antigen was heterogeneous in size and net charge. The possibility that 3 M KCl extracted a homogeneous population of molecules associating into polymers of various sizes at low ionic strength was ruled out by heterogeneity on Sephadex G-200 chromatography at high ionic strength. After osmotic lysis of sucrose-loaded line-10 cells, whole plasma membranes or large membrane fragments were obtained in a yield of about 20%. The isolation procedure did not cause detectable loss of membrane antigenic activity. The membranes had 33 skin test U/mg membrane protein, compared to the intact cell value of 1.7 skin test U/mg cell protein. Extracts of plasma membranes had 10-20% of the antigenic activity of the starting membrane material. In contrast to the wide variety of proteins liberated from intact cells, much of the protein extracted from the membranes was in the molecular weight range above 250,000."} {"id": "PMID:169369", "title": "An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.", "content": "One hundred ninety-six whole human breasts were examined by a subgross sampling technique with histologic confirmation. The method permitted the enumeration and identification of essentially all the focal dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesions. Of the 196, 119 were suitable for complete quantitative morphologic analysis of the focal lesions by type. They consisted of 67 breasts obtained by autopsy, 29 cancerous breasts obtained by mastectomy, and 23 contralateral to those with cancer. All lesions, photographed subgrossly, were subsequently confirmed and correlated histologically. Morphologic evidence supported the hypothesis that most lesions traditionally grouped as mammary dysplasia or fibrocystic disease, including apocrine cysts, sclerosing adenosis, fibroadenomas, various forms of lobules (sclerotic, dilated, hypersecretory, hyperplastic, atypical, or anaplastic), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), arose in terminal ductal-lobular units (TDLU) or in the lobules themselves. A probable exception was papilloma of ducts larger than terminal ones. Isolated foci of DCIS within the TDLU were seen in 40% of cancerous breasts, which indicated that the disease often was multifocal. Of the contralateral breasts, the 60% with clinical cancer contained such lesions, and data were in accord with the clinically known fact that women with previous breast cancer have a high rate of the disease in the remaining one. An atypical lobule (AL) of type A (ALA) had the following characteristics: a) It was more common in cancerous breasts or in those contralateral to cancer than in breasts not so identified; b) it had lobular morphology and was a terminal structure on the mammary tree; c) it tended to persist after the menopause, whereas normal lobules usually atrophied; d) it variable degrees of anaplasia forming an arbitrary continuum from normal lobules to ductal carcinoma in situ; and e) as ALA progressed to DCIS, the unfolded lobule resembled a duct which gave the false impression that DCIS was a ductal lesion. The morphologic evidence supported that hypothesis that the lesions herein called AL were derived from TDLU and were precancerous.", "contents": "An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. One hundred ninety-six whole human breasts were examined by a subgross sampling technique with histologic confirmation. The method permitted the enumeration and identification of essentially all the focal dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesions. Of the 196, 119 were suitable for complete quantitative morphologic analysis of the focal lesions by type. They consisted of 67 breasts obtained by autopsy, 29 cancerous breasts obtained by mastectomy, and 23 contralateral to those with cancer. All lesions, photographed subgrossly, were subsequently confirmed and correlated histologically. Morphologic evidence supported the hypothesis that most lesions traditionally grouped as mammary dysplasia or fibrocystic disease, including apocrine cysts, sclerosing adenosis, fibroadenomas, various forms of lobules (sclerotic, dilated, hypersecretory, hyperplastic, atypical, or anaplastic), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), arose in terminal ductal-lobular units (TDLU) or in the lobules themselves. A probable exception was papilloma of ducts larger than terminal ones. Isolated foci of DCIS within the TDLU were seen in 40% of cancerous breasts, which indicated that the disease often was multifocal. Of the contralateral breasts, the 60% with clinical cancer contained such lesions, and data were in accord with the clinically known fact that women with previous breast cancer have a high rate of the disease in the remaining one. An atypical lobule (AL) of type A (ALA) had the following characteristics: a) It was more common in cancerous breasts or in those contralateral to cancer than in breasts not so identified; b) it had lobular morphology and was a terminal structure on the mammary tree; c) it tended to persist after the menopause, whereas normal lobules usually atrophied; d) it variable degrees of anaplasia forming an arbitrary continuum from normal lobules to ductal carcinoma in situ; and e) as ALA progressed to DCIS, the unfolded lobule resembled a duct which gave the false impression that DCIS was a ductal lesion. The morphologic evidence supported that hypothesis that the lesions herein called AL were derived from TDLU and were precancerous."} {"id": "PMID:169370", "title": "Aerosolized BCG (Tice strain) treatment of bronchogenic carcinoma: phase I study.", "content": "Twenty patients with pathologically proved non-resectable bronchogenic carcinoma were treated with 100 aerosolized BCG (Tice strain) doses in addition to conventional treatment. The procedure is based on findings that, generally BCG must be closely associated with neoplastic cells to be effective as an immunotherapeutic agent. Bronchogenic malignancy, usually of mucosal origin, is logically treated in this manner. We report here the findings and developments of 10 patients who were treated at least five times each (for a total of 81 treatments) and pertinent experience relating to these and another 10 patients treated a total of 19 times. Local and systemic reactions were frequent and consisted of fever, cough, dyspnea, nausea, vomiting, anorexia, and malaise. Four of the 20 patients (20%) had reactions with the first treatment; by the fourth treatment 6 of 6 (100%) were affected. Prednisone given prophylactically reduced the intensity and the frequency of reactions. There were no severe side effects, obvious BCG infections, or significant changes in pulmonary or liver functions or hematologic values. No patient acquired purified protein derivative sensitivity, although 3 persons converted other skin tests to positive. There was no improvement in actuarial survival time.", "contents": "Aerosolized BCG (Tice strain) treatment of bronchogenic carcinoma: phase I study. Twenty patients with pathologically proved non-resectable bronchogenic carcinoma were treated with 100 aerosolized BCG (Tice strain) doses in addition to conventional treatment. The procedure is based on findings that, generally BCG must be closely associated with neoplastic cells to be effective as an immunotherapeutic agent. Bronchogenic malignancy, usually of mucosal origin, is logically treated in this manner. We report here the findings and developments of 10 patients who were treated at least five times each (for a total of 81 treatments) and pertinent experience relating to these and another 10 patients treated a total of 19 times. Local and systemic reactions were frequent and consisted of fever, cough, dyspnea, nausea, vomiting, anorexia, and malaise. Four of the 20 patients (20%) had reactions with the first treatment; by the fourth treatment 6 of 6 (100%) were affected. Prednisone given prophylactically reduced the intensity and the frequency of reactions. There were no severe side effects, obvious BCG infections, or significant changes in pulmonary or liver functions or hematologic values. No patient acquired purified protein derivative sensitivity, although 3 persons converted other skin tests to positive. There was no improvement in actuarial survival time."} {"id": "PMID:169371", "title": "Malignant tumors in American black and Nigerian children: a comparative study.", "content": "Results of a study on the relative frequencies of tumors in American black and Nigerian children were compared with data from the Childhood Cancer Registries in Manchester, United Kingdom, and Kampala, Uganda. The American black child living in Washington, D.C. and the Caucasian child living in Manchester had similar high frequencies for leukemia and glioma, whereas the incidence of lymphoma and retinoblastoma was low. African children living in Nigeria or Uganda had the opposite frequency patterns. These differences in frequencies of tumors between two ethnologically related population groups, American black and Nigerian, suggested the influence of environmental factors in the etiology of these tumors, even though exposure to environmental carcinogens was short. The rarity of Ewing's sarcoma and testicular tumors in American black and Nigerian children suggested a genetic influence.", "contents": "Malignant tumors in American black and Nigerian children: a comparative study. Results of a study on the relative frequencies of tumors in American black and Nigerian children were compared with data from the Childhood Cancer Registries in Manchester, United Kingdom, and Kampala, Uganda. The American black child living in Washington, D.C. and the Caucasian child living in Manchester had similar high frequencies for leukemia and glioma, whereas the incidence of lymphoma and retinoblastoma was low. African children living in Nigeria or Uganda had the opposite frequency patterns. These differences in frequencies of tumors between two ethnologically related population groups, American black and Nigerian, suggested the influence of environmental factors in the etiology of these tumors, even though exposure to environmental carcinogens was short. The rarity of Ewing's sarcoma and testicular tumors in American black and Nigerian children suggested a genetic influence."} {"id": "PMID:169372", "title": "Hemolytic anemia induced by murine erythroblastosis virus: possible mechanisms of hemolysis and effects of an interferon inducer.", "content": "Murine erythroblastosis virus (MuEV), also called murine leukemia virus-Kirsten, is a member of the murine type-C-RNA leukemia-sarcoma group of oncogenic viruses. Like other members of this group, MuEV can elicit both a hemolytic disorder and an oncogenic response. Neonatal rats infected with MuEV succumb to this hemolytic disorder unless they are treated with the synthetic double-stranded polyribonucleotide, polyinosinic-polycytidylic acid (poly I-poly C). Animals receiving poly I-poly C had markedly reduced levels of virus reproduction as measured by bioassay and electron microscopy. The proliferation of erythroblasts after MuEV infection in animals not receiving poly I-poly C appeared to be an erythropoietin-dependent compensatory response to hemolysis. The hemolysis itself seemed to require virus reproduction in the cell types affected. Administration of poly I-poly C to MuEV-infected rats inhibited virus reproduction and thus may circumvent the hemolytic disease syndrome. The ultrastructure of the virus and of the virus reproduction was also studied.", "contents": "Hemolytic anemia induced by murine erythroblastosis virus: possible mechanisms of hemolysis and effects of an interferon inducer. Murine erythroblastosis virus (MuEV), also called murine leukemia virus-Kirsten, is a member of the murine type-C-RNA leukemia-sarcoma group of oncogenic viruses. Like other members of this group, MuEV can elicit both a hemolytic disorder and an oncogenic response. Neonatal rats infected with MuEV succumb to this hemolytic disorder unless they are treated with the synthetic double-stranded polyribonucleotide, polyinosinic-polycytidylic acid (poly I-poly C). Animals receiving poly I-poly C had markedly reduced levels of virus reproduction as measured by bioassay and electron microscopy. The proliferation of erythroblasts after MuEV infection in animals not receiving poly I-poly C appeared to be an erythropoietin-dependent compensatory response to hemolysis. The hemolysis itself seemed to require virus reproduction in the cell types affected. Administration of poly I-poly C to MuEV-infected rats inhibited virus reproduction and thus may circumvent the hemolytic disease syndrome. The ultrastructure of the virus and of the virus reproduction was also studied."} {"id": "PMID:169373", "title": "Inhibitory effect of adult bovine serum on release of infectious Epstein-Barr virus from a virus-carrier cell line.", "content": "When certain bovine sera (BS) were used to culture P3HR-1 cells, the amount of infectious Epstein-Barr virus (EBV) released into the culture fluid was significantly less than that obtained when calf serum (CS) or fetal calf serum (FCS) was used. A direct dose-response relationship was noted between the concentration of BS and the degree of inhibition of virus production. Cell growth was not inhibited nor was virus infectivity neutralized by BS. Similarly, EBV infectivity was not reduced by spent medium containing BS. The inhibition of virus production by BS could be reversed by replacement of the serum supplement with CS. The formation of viral capsid antigen and of infectious virus within the cells was not inhibited by BS, whereas the amount of virus released was significantly decreased in comparison with culture media containing FCS or CS. These findings suggested the presence of a factor(s) in the BS which inhibited the release of EBV from the cell.", "contents": "Inhibitory effect of adult bovine serum on release of infectious Epstein-Barr virus from a virus-carrier cell line. When certain bovine sera (BS) were used to culture P3HR-1 cells, the amount of infectious Epstein-Barr virus (EBV) released into the culture fluid was significantly less than that obtained when calf serum (CS) or fetal calf serum (FCS) was used. A direct dose-response relationship was noted between the concentration of BS and the degree of inhibition of virus production. Cell growth was not inhibited nor was virus infectivity neutralized by BS. Similarly, EBV infectivity was not reduced by spent medium containing BS. The inhibition of virus production by BS could be reversed by replacement of the serum supplement with CS. The formation of viral capsid antigen and of infectious virus within the cells was not inhibited by BS, whereas the amount of virus released was significantly decreased in comparison with culture media containing FCS or CS. These findings suggested the presence of a factor(s) in the BS which inhibited the release of EBV from the cell."} {"id": "PMID:169374", "title": "Establishment of two canine sarcoma cell lines: productive infection with feline leukemia virus.", "content": "Two canine sarcoma cell lines (11028, 11031) were established in vitro and have been transferred 213 and 306 times, respectively, since 1970. These cell lines had a chromosome pattern consistent with their canine origin. Both cultures were infected with feline leukemia virus (FeLV), which caused a morphologic and karyotypic changes. The cells became rounded after infection with FeLV and both cultures showed the presence of a single, large, acrocentric chromosome considered to be a marker chromosome. All tumors were transplanted into newborn beagle pups, but only the 11028-FeLV formed metastatic tumors. No helper or focus-forming activity or virus particles were found in the uninfected cultures. Helper activity and virus were demonstrated in both sarcoma lines after infection with FeLV, though no focus-forming activity was noted. Helper activity of progeny virus could be assayed on either cat or dog embryo cells.", "contents": "Establishment of two canine sarcoma cell lines: productive infection with feline leukemia virus. Two canine sarcoma cell lines (11028, 11031) were established in vitro and have been transferred 213 and 306 times, respectively, since 1970. These cell lines had a chromosome pattern consistent with their canine origin. Both cultures were infected with feline leukemia virus (FeLV), which caused a morphologic and karyotypic changes. The cells became rounded after infection with FeLV and both cultures showed the presence of a single, large, acrocentric chromosome considered to be a marker chromosome. All tumors were transplanted into newborn beagle pups, but only the 11028-FeLV formed metastatic tumors. No helper or focus-forming activity or virus particles were found in the uninfected cultures. Helper activity and virus were demonstrated in both sarcoma lines after infection with FeLV, though no focus-forming activity was noted. Helper activity of progeny virus could be assayed on either cat or dog embryo cells."} {"id": "PMID:169375", "title": "Effect of BCG on dimethylhydrazine induction of colon tumors in rats.", "content": "The effect of BCG injection into the colon wall on the induction of colon tumors by 1,2-dimethylhydrazine dihydrochloride (DMH) was assessed in male rats. Persistent, generalized BCG infection followed the intracolonic injection of 6.7 times 10(6) organisms in otherwise untreated rats. In rats given DMH (30 mg/kg/wk) intragastrically for 5 weeks and then infected with BCG, colon tumors developed at the same rate and in the same incidence as in uninfected rats, but more tumors were mucinous adenocarcinomas and metastasized to the abdominal lymph nodes. In a few rats with large, established colon tumors, the injection of BCG into tumors induced no apparent change in them when examined at autopsy 1-22 weeks later.", "contents": "Effect of BCG on dimethylhydrazine induction of colon tumors in rats. The effect of BCG injection into the colon wall on the induction of colon tumors by 1,2-dimethylhydrazine dihydrochloride (DMH) was assessed in male rats. Persistent, generalized BCG infection followed the intracolonic injection of 6.7 times 10(6) organisms in otherwise untreated rats. In rats given DMH (30 mg/kg/wk) intragastrically for 5 weeks and then infected with BCG, colon tumors developed at the same rate and in the same incidence as in uninfected rats, but more tumors were mucinous adenocarcinomas and metastasized to the abdominal lymph nodes. In a few rats with large, established colon tumors, the injection of BCG into tumors induced no apparent change in them when examined at autopsy 1-22 weeks later."} {"id": "PMID:169376", "title": "Lymphocytes and leukemia viruses: tropism and transtropism of murine leukemia virus.", "content": "The tropism of naturally occurring murine leukemia virus (MuLV) was investigated in short-term lymphocyte cultures. The tropism of MuLV was readily defined in fibroblast cultures, but not in lymphocyte cultures. Lymphocytes free of infectious MuLV could be infected across the tropism barrier by partially purified MuLv or by in vitro contact with MuLV-producing lymphocytes. Stimulation of lymphocytes was not required for this cross-infection and replication of MuLV. When cross-infected lymphocytes and was specifically associated with lymphocytes were stimulated in vitro by allogeneic cells, they facilitated MuLV infection of ordinarily non-permissive fibroblasts. This phenomenon (transtropism) required antigenically stimulated lymphocytes and was specifically associated with infection of the lymphocyte by MuLV across the tropism barrier. Thus in contrast with the resting lymphocyte, the transformed lymphocyte acquired the ability to disseminate infectious MuLV to nonpermissive cells. These findings suggest a novel relationship between lymphocytes and leukemia viruses. They indicate one mechanism whereby antigenic stimulation may enhance the development of virus-induced lymphoid neoplasms.", "contents": "Lymphocytes and leukemia viruses: tropism and transtropism of murine leukemia virus. The tropism of naturally occurring murine leukemia virus (MuLV) was investigated in short-term lymphocyte cultures. The tropism of MuLV was readily defined in fibroblast cultures, but not in lymphocyte cultures. Lymphocytes free of infectious MuLV could be infected across the tropism barrier by partially purified MuLv or by in vitro contact with MuLV-producing lymphocytes. Stimulation of lymphocytes was not required for this cross-infection and replication of MuLV. When cross-infected lymphocytes and was specifically associated with lymphocytes were stimulated in vitro by allogeneic cells, they facilitated MuLV infection of ordinarily non-permissive fibroblasts. This phenomenon (transtropism) required antigenically stimulated lymphocytes and was specifically associated with infection of the lymphocyte by MuLV across the tropism barrier. Thus in contrast with the resting lymphocyte, the transformed lymphocyte acquired the ability to disseminate infectious MuLV to nonpermissive cells. These findings suggest a novel relationship between lymphocytes and leukemia viruses. They indicate one mechanism whereby antigenic stimulation may enhance the development of virus-induced lymphoid neoplasms."} {"id": "PMID:169377", "title": "Feline oncornavirus-associated cell membrane antigen. IV. Antibody titers in cats with naturally occurring leukemia, lymphoma, and other diseases.", "content": "Cats with naturally occurring leukemia and lymphoma had low or negative humoral antibody titers to the feline oncornavirus-associated cell membrane antigen (FOCMA). Geographic differences were seen in the relative frequencies of various forms of lymphoproliferative neoplasms. Lymphatic leukemia and thymic lymphoma were most common in Boston, whereas alimentary lymphoma was most frequent in Glasgow. No significant differences were found in geometric mean FOCMA antibody titers for the various forms of leukemia-lymphoma or for feline leukemia virus (FeLV)-positive as compared to FeLV-negative cats. Approximately 70% of 76 Boston cats with nonregenerative anemias were FeLV gs antigen (gsa) positive; this was similar to the percentage with leukemia-lymphoma from the same population that was positive. Fifty-five to 62% of the Boston cats with other infectious diseases, such as peritonitis and septicemia, were gsa positive. We postulate that this is due to a predisposition to infectious diseases by the immunosuppressive action of FeLV. Young cats from the Boston population that developed lymphoma, infectious peritonitis, and certain other diseases were more likely to be FeLV gsa positive than older cats with the same diseases.", "contents": "Feline oncornavirus-associated cell membrane antigen. IV. Antibody titers in cats with naturally occurring leukemia, lymphoma, and other diseases. Cats with naturally occurring leukemia and lymphoma had low or negative humoral antibody titers to the feline oncornavirus-associated cell membrane antigen (FOCMA). Geographic differences were seen in the relative frequencies of various forms of lymphoproliferative neoplasms. Lymphatic leukemia and thymic lymphoma were most common in Boston, whereas alimentary lymphoma was most frequent in Glasgow. No significant differences were found in geometric mean FOCMA antibody titers for the various forms of leukemia-lymphoma or for feline leukemia virus (FeLV)-positive as compared to FeLV-negative cats. Approximately 70% of 76 Boston cats with nonregenerative anemias were FeLV gs antigen (gsa) positive; this was similar to the percentage with leukemia-lymphoma from the same population that was positive. Fifty-five to 62% of the Boston cats with other infectious diseases, such as peritonitis and septicemia, were gsa positive. We postulate that this is due to a predisposition to infectious diseases by the immunosuppressive action of FeLV. Young cats from the Boston population that developed lymphoma, infectious peritonitis, and certain other diseases were more likely to be FeLV gsa positive than older cats with the same diseases."} {"id": "PMID:169378", "title": "Antitumor effects of antibody-diphtheria toxin conjugates. II. Immunotherapy with conjugates directed against tumor antigens induced by simian virus 40.", "content": "Hamster and rabbit antibodies against antigens on the surface of simian virus 40 (SV40)-transformed hamster sarcoma or lymphoma cells were purified by immunoadsorption on SV40-transformed cells and conjugated to diphtheria toxin with glutaraldehyde. Treatment with a single dose of antibody-toxin conjugate partially protected hamsters concurrently challenged with 10(3) SV40-transformed sarcoma cells, as evidenced by a reduction in tumor incidence, an increase in tumor latency, and a prolongation of the life-spans of hamsters that developed tumors. Treatment of established sarcomas was ineffective, but repeated treatment with the conjugates induced complete regressions in 20-56% of hamsters bearing established transplants in the SV40-induced lymphoma.", "contents": "Antitumor effects of antibody-diphtheria toxin conjugates. II. Immunotherapy with conjugates directed against tumor antigens induced by simian virus 40. Hamster and rabbit antibodies against antigens on the surface of simian virus 40 (SV40)-transformed hamster sarcoma or lymphoma cells were purified by immunoadsorption on SV40-transformed cells and conjugated to diphtheria toxin with glutaraldehyde. Treatment with a single dose of antibody-toxin conjugate partially protected hamsters concurrently challenged with 10(3) SV40-transformed sarcoma cells, as evidenced by a reduction in tumor incidence, an increase in tumor latency, and a prolongation of the life-spans of hamsters that developed tumors. Treatment of established sarcomas was ineffective, but repeated treatment with the conjugates induced complete regressions in 20-56% of hamsters bearing established transplants in the SV40-induced lymphoma."} {"id": "PMID:169379", "title": "Effect of host age, virus dose, and route of inoculation on tumor incidence, latency, and morphology in Syrian hamsters inoculated intravenously with oncogenic DNA simian virus 40.", "content": "Three-week-old to 12-month-old male Syrian hamsters were inoculated iv with 10(8.5) median tissue culture infective dose of simian virus 40 (SV40). Three-week-old hamsters were similarly inoculated with aliquots of SV40 of progressively decreasing titers. The tumor incidence and, to a lesser extent, the tumor latency were directly dependent on the age of the animals at the time of virus exposure and on the dose of the virus. However, this age-dose dependence was not of the magnitude usually observed in hamsters inoculated with SV40 sc or im. Moreover, the wide morphologic spectrum of neoplasms induced, i.e., lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma, by iv route of inoculation, contrasted sharply with the anaplastic and spindle-cell sarcomas which were the only types of malignant tumors resulting when other routes were used.", "contents": "Effect of host age, virus dose, and route of inoculation on tumor incidence, latency, and morphology in Syrian hamsters inoculated intravenously with oncogenic DNA simian virus 40. Three-week-old to 12-month-old male Syrian hamsters were inoculated iv with 10(8.5) median tissue culture infective dose of simian virus 40 (SV40). Three-week-old hamsters were similarly inoculated with aliquots of SV40 of progressively decreasing titers. The tumor incidence and, to a lesser extent, the tumor latency were directly dependent on the age of the animals at the time of virus exposure and on the dose of the virus. However, this age-dose dependence was not of the magnitude usually observed in hamsters inoculated with SV40 sc or im. Moreover, the wide morphologic spectrum of neoplasms induced, i.e., lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma, by iv route of inoculation, contrasted sharply with the anaplastic and spindle-cell sarcomas which were the only types of malignant tumors resulting when other routes were used."} {"id": "PMID:169380", "title": "Mouse mammary tumor virus polypeptide precursors in intracytoplasmic A particles.", "content": "Intracytoplasmic A particles were analyzed by immunodiffusion and sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) before and after enzymatic cleavage with trypsin. A common antigen in A particles was detected by antisera prepared against purified intracytoplasmic A particles, purified mouse mammary tumor virus (MMTV), and a purified MMTV core polypeptide (p28). Despite this correlation, no SDS--polyacrylamide band migrating at p28 was observed in purified intracytoplasmic A particles. However, after incubation with trypsin, A particles subjected to SDS--PAGE produced only two polypeptide bands. They were observed at p28 and p15-10. Ouchterlony analysis of the trypsin-cleaved A particles revealed no alteration in the antigenicity of the particles. These results suggested that some structural components of intracytoplasmic A particles are polypeptide precursors of MMTV core proteins.", "contents": "Mouse mammary tumor virus polypeptide precursors in intracytoplasmic A particles. Intracytoplasmic A particles were analyzed by immunodiffusion and sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) before and after enzymatic cleavage with trypsin. A common antigen in A particles was detected by antisera prepared against purified intracytoplasmic A particles, purified mouse mammary tumor virus (MMTV), and a purified MMTV core polypeptide (p28). Despite this correlation, no SDS--polyacrylamide band migrating at p28 was observed in purified intracytoplasmic A particles. However, after incubation with trypsin, A particles subjected to SDS--PAGE produced only two polypeptide bands. They were observed at p28 and p15-10. Ouchterlony analysis of the trypsin-cleaved A particles revealed no alteration in the antigenicity of the particles. These results suggested that some structural components of intracytoplasmic A particles are polypeptide precursors of MMTV core proteins."} {"id": "PMID:169381", "title": "Estrogen receptor assay in human breast cancer.", "content": "A Workshop on Receptor Assay in Breast Cancer Tissue at the Fourth International Congress on Hormonal Steroids was held in Mexico City, September 2-7, 1974. This report reviews the various methods of steroid receptor assay in breast cancer discussed at this Workshop.", "contents": "Estrogen receptor assay in human breast cancer. A Workshop on Receptor Assay in Breast Cancer Tissue at the Fourth International Congress on Hormonal Steroids was held in Mexico City, September 2-7, 1974. This report reviews the various methods of steroid receptor assay in breast cancer discussed at this Workshop."} {"id": "PMID:169382", "title": "Low oncogenic potential of avian endogenous RNA tumor virus infection or expression.", "content": "Of chickens either spontaneously producing or exogenously infected in ovo with Rous-associated virus, type O (RAV-O), an endogenous virus of the chicken, only 1 died with lymphoid leukosis (LL), the most common neoplasm associated with the leukosis-sarcoma virus group. Because the chickens were not kept in strict isolation, it could not be assumed that the one LL was induced by RAV-O. In contrast, RAV-1-infected chickens from the same lines had a high incidence of LL and other neoplasms. Over 800 chickens of several inbred lines were maintained in plastic isolators free of exogenous avian leukosis-sarcoma virus infection for from 500 to nearly 1,000 days of age. No LL was observed, even though some lines are known to produce RAV-O spontaneously or to express inherited gs antigen. Three neoplasms of unknown etiology were observed, but none generally associated with leukosis virus infection. We concluded that avian endogenous virus expression had little, if any, oncogenic potential, and that exogenous avian leukosis viruses were responsible for most naturally occurring neoplasms.", "contents": "Low oncogenic potential of avian endogenous RNA tumor virus infection or expression. Of chickens either spontaneously producing or exogenously infected in ovo with Rous-associated virus, type O (RAV-O), an endogenous virus of the chicken, only 1 died with lymphoid leukosis (LL), the most common neoplasm associated with the leukosis-sarcoma virus group. Because the chickens were not kept in strict isolation, it could not be assumed that the one LL was induced by RAV-O. In contrast, RAV-1-infected chickens from the same lines had a high incidence of LL and other neoplasms. Over 800 chickens of several inbred lines were maintained in plastic isolators free of exogenous avian leukosis-sarcoma virus infection for from 500 to nearly 1,000 days of age. No LL was observed, even though some lines are known to produce RAV-O spontaneously or to express inherited gs antigen. Three neoplasms of unknown etiology were observed, but none generally associated with leukosis virus infection. We concluded that avian endogenous virus expression had little, if any, oncogenic potential, and that exogenous avian leukosis viruses were responsible for most naturally occurring neoplasms."} {"id": "PMID:169383", "title": "Ecotropic leukemia viruses in congenic C57BL mice: natural dissemination by milk-borne infection.", "content": "The incidence of infectious murine leukemia virus (MuLV) in congenic-resistant C57BL mice was studied. No constant relationship between the incidence of MuLV and the H-2 complex was apparent. Two lines, B10 and B10.A, were examined in detail because the incidence of MuLV in B10 was low and the virus appeared relatively late in life, whereas B10.A animals had a relatively high incidence of infection by MuLV early in life. Further studies of B10.A mice revealed an almost universal concordance between the virologic status of the mother and her offspring. This was particularly evident when (B10 times B10.A)F1 animals were compared with (B10.A times B10)F1 mice: Although genetically identical, the incidence of MuLV in the latter was high, whereas in the former it was low. Transmission of MuLV by milk was proved by foster-nursing experiments; when the infants of MuLV-positive B10.A mothers were suckled on MuLV-negative B10.A mothers, they were free of MuLV. Milk-borne infection may account for the natural dissemination of MuLV among some inbred lines of mice.", "contents": "Ecotropic leukemia viruses in congenic C57BL mice: natural dissemination by milk-borne infection. The incidence of infectious murine leukemia virus (MuLV) in congenic-resistant C57BL mice was studied. No constant relationship between the incidence of MuLV and the H-2 complex was apparent. Two lines, B10 and B10.A, were examined in detail because the incidence of MuLV in B10 was low and the virus appeared relatively late in life, whereas B10.A animals had a relatively high incidence of infection by MuLV early in life. Further studies of B10.A mice revealed an almost universal concordance between the virologic status of the mother and her offspring. This was particularly evident when (B10 times B10.A)F1 animals were compared with (B10.A times B10)F1 mice: Although genetically identical, the incidence of MuLV in the latter was high, whereas in the former it was low. Transmission of MuLV by milk was proved by foster-nursing experiments; when the infants of MuLV-positive B10.A mothers were suckled on MuLV-negative B10.A mothers, they were free of MuLV. Milk-borne infection may account for the natural dissemination of MuLV among some inbred lines of mice."} {"id": "PMID:169384", "title": "C-type viruses in chimpanzee (Pan sp.) placentas.", "content": "C-type virus particles were observed by electron microscopy in placentas from 7 of 9 chimpanzees (Pan sp.). These viruses were morphologically similar to those observed in placentas of other primates.", "contents": "C-type viruses in chimpanzee (Pan sp.) placentas. C-type virus particles were observed by electron microscopy in placentas from 7 of 9 chimpanzees (Pan sp.). These viruses were morphologically similar to those observed in placentas of other primates."} {"id": "PMID:169387", "title": "Mitochondrial and herpesvirus-specific deoxypyrimidine kinases.", "content": "To characterize and compare the thymidine (TdR) and deoxycytidine (CdR) kinase isozymes of uninfected and herpesvirus-infected cells: (i) the subcellular distribution of the isozymes has been studied; (ii) a specific assay for CdR kinase has been devised; (iii) the TdR kinase isozymes have been partially purified; and (iv) the purified enzymes have been analyzed by disc polyacrylamide gel electrophoresis, isoelectric focusing, and glycerol gradient centrifugation and by substrate competition and dCTP inhibition studies. The results indicate that there are interesting individual differences with respect to nucleoside acceptor specificity between the cytosol and mitochondrial pyrimidine deoxyribonucleoside kinases of uninfected cells and between the enzymes induced by different herpesviruses. In the cytosol of uninfected mouse, chicken, and owl monkey kidney cells, two different proteins, TdR kinase F and CdR kinase 2, catalyze the phosphorylations of TdR and CdR, respectively. TdR kinase F does not phosphorylate CdR, nor does CdR kinase 2 phosphorylate TdR. A second TdR kinase isozyme present in HeLa(BU25) mitochondria (TdR kinase B) also lacks CdR phosphorylating activity. In contrast, a genetically distinctive deoxypyrimidine kinase (TdR kinase A) of mouse, human, and chick mitochondria catalyzes the phosphorylation of both TdR and CdT. Three herpesviruses, marmoset herpesvirus and herpes simplex virus types 1 and 2, induce in the cytosol fraction of LM(TK-) mouse cells isozymes which share common properties with mitochondrial TdR kinase A, including the ability to catalyze the phosphorylation of both TdR and CdR. However, the herpesvirus-induced deoxypyrimidine kinases differ from mitochondrial TdR kinase A with respect to sedimentation coefficient, sensitivity to dCTP inhibition, and antigenic determinants. The herpesvirus-specific and the mitochondrial deoxypyrimidine kinases exhibit a preference for TdR over CdR as nucleoside acceptor. Pseudorabies virus and herpesvirus of turkeys induce cytosol TdR kinases resembling the other herpesvirus-induced TdR kinases in several properties, but like cellular TdR kinase F, the pseudorabies virus and herpesvirus of turkeys TdR kinases lack detectable CdR phosphorylating activities. Finally, a marmoset herpesvirus nutant resistant to bromodeoxyuridine, equine herpesvirus type 1, and Herpesvirus aotus induces neither TdR nor CdR phosphorylating enzymes during productive infections.", "contents": "Mitochondrial and herpesvirus-specific deoxypyrimidine kinases. To characterize and compare the thymidine (TdR) and deoxycytidine (CdR) kinase isozymes of uninfected and herpesvirus-infected cells: (i) the subcellular distribution of the isozymes has been studied; (ii) a specific assay for CdR kinase has been devised; (iii) the TdR kinase isozymes have been partially purified; and (iv) the purified enzymes have been analyzed by disc polyacrylamide gel electrophoresis, isoelectric focusing, and glycerol gradient centrifugation and by substrate competition and dCTP inhibition studies. The results indicate that there are interesting individual differences with respect to nucleoside acceptor specificity between the cytosol and mitochondrial pyrimidine deoxyribonucleoside kinases of uninfected cells and between the enzymes induced by different herpesviruses. In the cytosol of uninfected mouse, chicken, and owl monkey kidney cells, two different proteins, TdR kinase F and CdR kinase 2, catalyze the phosphorylations of TdR and CdR, respectively. TdR kinase F does not phosphorylate CdR, nor does CdR kinase 2 phosphorylate TdR. A second TdR kinase isozyme present in HeLa(BU25) mitochondria (TdR kinase B) also lacks CdR phosphorylating activity. In contrast, a genetically distinctive deoxypyrimidine kinase (TdR kinase A) of mouse, human, and chick mitochondria catalyzes the phosphorylation of both TdR and CdT. Three herpesviruses, marmoset herpesvirus and herpes simplex virus types 1 and 2, induce in the cytosol fraction of LM(TK-) mouse cells isozymes which share common properties with mitochondrial TdR kinase A, including the ability to catalyze the phosphorylation of both TdR and CdR. However, the herpesvirus-induced deoxypyrimidine kinases differ from mitochondrial TdR kinase A with respect to sedimentation coefficient, sensitivity to dCTP inhibition, and antigenic determinants. The herpesvirus-specific and the mitochondrial deoxypyrimidine kinases exhibit a preference for TdR over CdR as nucleoside acceptor. Pseudorabies virus and herpesvirus of turkeys induce cytosol TdR kinases resembling the other herpesvirus-induced TdR kinases in several properties, but like cellular TdR kinase F, the pseudorabies virus and herpesvirus of turkeys TdR kinases lack detectable CdR phosphorylating activities. Finally, a marmoset herpesvirus nutant resistant to bromodeoxyuridine, equine herpesvirus type 1, and Herpesvirus aotus induces neither TdR nor CdR phosphorylating enzymes during productive infections."} {"id": "PMID:169388", "title": "DNA synthesis and DNA polymerase activity of herpes simplex virus type 1 temperature-sensitive mutants.", "content": "Fifteen temperature-sensitive mutants of herpes simplex virus type 1 were studied with regard to the relationship between their ability to synthesize viral DNA and to induce viral DNA polymerase (DP) activity at permissive (34 C) and nonpermissive (39 C) temperatures. At 34 C, all mutants synthesized viral DNA, while at 39 C four mutants demonstrated a DNA+ phenotype, three were DNA+/-, and eight were DNA-. DNA+ mutants induced levels of DP activity similar to thhose of the wild-type virus at both temperatures, and DNA+/- mutants induced reduced levels of DP activity at 39 C but not at 34 C. Among the DNA- mutants three were DP+, two were DP+/-, and three showed reduced DP activity at 34 C with no DP activity at 39 C. DNA-, DP- mutants induced the synthesis of a temperature-sensitive DP as determined by in vivo studies.", "contents": "DNA synthesis and DNA polymerase activity of herpes simplex virus type 1 temperature-sensitive mutants. Fifteen temperature-sensitive mutants of herpes simplex virus type 1 were studied with regard to the relationship between their ability to synthesize viral DNA and to induce viral DNA polymerase (DP) activity at permissive (34 C) and nonpermissive (39 C) temperatures. At 34 C, all mutants synthesized viral DNA, while at 39 C four mutants demonstrated a DNA+ phenotype, three were DNA+/-, and eight were DNA-. DNA+ mutants induced levels of DP activity similar to thhose of the wild-type virus at both temperatures, and DNA+/- mutants induced reduced levels of DP activity at 39 C but not at 34 C. Among the DNA- mutants three were DP+, two were DP+/-, and three showed reduced DP activity at 34 C with no DP activity at 39 C. DNA-, DP- mutants induced the synthesis of a temperature-sensitive DP as determined by in vivo studies."} {"id": "PMID:169389", "title": "Properties of feline leukemia virus. III. Analysis of the RNA.", "content": "The kinetics of virus labeling was used to study the maturation of viral RNA in the Rickard strain of feline leukemia virus. Viral RNA labeled over differing intervals was characterized by gel electrophoresis and velocity sedimentation in sucrose gradients made up in aqueous buffer and 99% dimethyl sulfoxide. Labeled virus was found within 30 min after adding radioactive uridine to the cells and production of labeled virus reached a maximum at 4 to 5 h after pulse labeling. Native RNA from feline leukemia virus resolved into three size classes when analyzed by electrophoresis on 2.0% polyacrylamide-0.5% agarose gels: a 6.2 x 10(6) to 7.1 x 10(6) mol wt (50 to 60S) class, an 8.7 x 10(4) mol wt (approximately 8S) class, and a 2.5 x 10(4) mol wt (4 to 5S) class. From two experiments during which RNA degradation appeared minimal, these made up to 57 to 76%, 2 to 5%, and 6 to 12%, respectively, of the total RNA. The 8S RNA in feline leukemia virus has not previously been reported. The 50 to 60S RNA from virus harvested after 4 h of labeling electrophoretically migrated faster and sedimented more slowly in sucrose gradients than did the same RNA species harvested after 20 h of labeling. This argues for an intravirion modification of the high-molecular-weight RNA. The large subunits of denatured viral RNA from both 4- and 20-h labeled-viral RNA electrophoretically migrated with an estimated molecular weight of 3.2 x 10(6) but sedimented with 28S ribosomal RNA (1.8 X 10(6) mol wt) when analyzed by velocity sedimentation through 99% dimethyl sulfoxide.", "contents": "Properties of feline leukemia virus. III. Analysis of the RNA. The kinetics of virus labeling was used to study the maturation of viral RNA in the Rickard strain of feline leukemia virus. Viral RNA labeled over differing intervals was characterized by gel electrophoresis and velocity sedimentation in sucrose gradients made up in aqueous buffer and 99% dimethyl sulfoxide. Labeled virus was found within 30 min after adding radioactive uridine to the cells and production of labeled virus reached a maximum at 4 to 5 h after pulse labeling. Native RNA from feline leukemia virus resolved into three size classes when analyzed by electrophoresis on 2.0% polyacrylamide-0.5% agarose gels: a 6.2 x 10(6) to 7.1 x 10(6) mol wt (50 to 60S) class, an 8.7 x 10(4) mol wt (approximately 8S) class, and a 2.5 x 10(4) mol wt (4 to 5S) class. From two experiments during which RNA degradation appeared minimal, these made up to 57 to 76%, 2 to 5%, and 6 to 12%, respectively, of the total RNA. The 8S RNA in feline leukemia virus has not previously been reported. The 50 to 60S RNA from virus harvested after 4 h of labeling electrophoretically migrated faster and sedimented more slowly in sucrose gradients than did the same RNA species harvested after 20 h of labeling. This argues for an intravirion modification of the high-molecular-weight RNA. The large subunits of denatured viral RNA from both 4- and 20-h labeled-viral RNA electrophoretically migrated with an estimated molecular weight of 3.2 x 10(6) but sedimented with 28S ribosomal RNA (1.8 X 10(6) mol wt) when analyzed by velocity sedimentation through 99% dimethyl sulfoxide."} {"id": "PMID:169390", "title": "Site on the RNA of an avian sarcoma virus at which primer is bound.", "content": "In vitro transcription of the avian tumor virus RNA by RNA-directed DNA polymerase is initiated on the unique cellular 4S RNA. Previous studies have shown that on the average there is one such RNA primer hydrogen bonded to each viral 35S RNA. The present study confirms that finding and demonstrates that, at least for the majority of 35S RNA molecules, the primer is bound at a site close to the 5'-terminus.", "contents": "Site on the RNA of an avian sarcoma virus at which primer is bound. In vitro transcription of the avian tumor virus RNA by RNA-directed DNA polymerase is initiated on the unique cellular 4S RNA. Previous studies have shown that on the average there is one such RNA primer hydrogen bonded to each viral 35S RNA. The present study confirms that finding and demonstrates that, at least for the majority of 35S RNA molecules, the primer is bound at a site close to the 5'-terminus."} {"id": "PMID:169391", "title": "Escherichia coli capsule bacteriophages. IV. Primary structure of the bacteriophage 29 receptor, the E. coli serotype 29 capsular polysaccharide.", "content": "Using periodate oxidation, methylation analysis, characterization of oligosaccharides by Smith degradation or partial acid hydrolysis, as well as proton magnetic resonance, the primary structure of the Escherichia coli serotype 29 capsular polysaccharide (the receptor of E. coli K phage 29) was reinvestigated. The polymer was found to consist of hexasaccharide repeating units of the following structure: (see article).", "contents": "Escherichia coli capsule bacteriophages. IV. Primary structure of the bacteriophage 29 receptor, the E. coli serotype 29 capsular polysaccharide. Using periodate oxidation, methylation analysis, characterization of oligosaccharides by Smith degradation or partial acid hydrolysis, as well as proton magnetic resonance, the primary structure of the Escherichia coli serotype 29 capsular polysaccharide (the receptor of E. coli K phage 29) was reinvestigated. The polymer was found to consist of hexasaccharide repeating units of the following structure: (see article)."} {"id": "PMID:169392", "title": "Adenovirus transcription. II. RNA sequences complementary to simian virus 40 and adenovirus 2DNA in AD2+ND1- and AD2+ND3-infected cells.", "content": "The genomes of the two nondefective adenovirus 2/simian virus 40 (Ad2/SV 40) hybrid viruses, nondefective Ad2/SV 40 hybrid virus 1 (Ad2+ND1) and nondefective hybrid virus 3 (Ad2+ND3), WERE FORMED BY A DELETION OF ABOUT 5% OF Ad2 DNA and insertion of part of the SV40 genome. We have compared the cytoplasmic RNA synthesized during both the early and late stages of lytic infection of human cells by these hybrid viruses to that expressed in Ad2-infected and SV40-infected cells. Separated strands of the six fragments of 32P-labeled Ad2 DNA produced by cleavage with the restriction endonuclease EcoRI (isolated from Escherichia coli) and the four fragments of 32P-labeled SV40 DNA produced by cleavage with both a restriction nuclease isolated from Haemophilus parainfluenzae, Hpa1, and EcoRI were prepared by electrophoresis of denatured DNA in agarose gels. The fraction of each fragment strand expressed as cytoplasmic RNA was determined by annealing fragmented 32P-labeled strands to an excess of cellular RNA extracted from infected cells. The segment of Ad2 DNA deleted from both hybrid virus genomes is transcribed into cytoplasmic mRNA during the early phase of Ad2 infection. Hence, we suggest that Ad2 codes for at least one \"early\" gene product which is nonessential for virus growth in cell culture. In both early Ad2+ND1 and Ad2+ND3-infected cells, 1,000 bases of Ad2 DNA adjacent to the integrated SV40 sequences are expressed as cytoplasmic RNA but are not similarly expressed in early Ad2-infected cells. The 3' termini of this early hybrid virus RNA maps in the vicinity of 0.18 on the conventional SV40 map and probably terminates at the same position as early lytic SV40 cytoplasmic RNA. Therefore, the base sequence in this region of SV40 DNA specifies the 3' termini of early messenger RNA present in both hybrid virus and SV40-infected cells.", "contents": "Adenovirus transcription. II. RNA sequences complementary to simian virus 40 and adenovirus 2DNA in AD2+ND1- and AD2+ND3-infected cells. The genomes of the two nondefective adenovirus 2/simian virus 40 (Ad2/SV 40) hybrid viruses, nondefective Ad2/SV 40 hybrid virus 1 (Ad2+ND1) and nondefective hybrid virus 3 (Ad2+ND3), WERE FORMED BY A DELETION OF ABOUT 5% OF Ad2 DNA and insertion of part of the SV40 genome. We have compared the cytoplasmic RNA synthesized during both the early and late stages of lytic infection of human cells by these hybrid viruses to that expressed in Ad2-infected and SV40-infected cells. Separated strands of the six fragments of 32P-labeled Ad2 DNA produced by cleavage with the restriction endonuclease EcoRI (isolated from Escherichia coli) and the four fragments of 32P-labeled SV40 DNA produced by cleavage with both a restriction nuclease isolated from Haemophilus parainfluenzae, Hpa1, and EcoRI were prepared by electrophoresis of denatured DNA in agarose gels. The fraction of each fragment strand expressed as cytoplasmic RNA was determined by annealing fragmented 32P-labeled strands to an excess of cellular RNA extracted from infected cells. The segment of Ad2 DNA deleted from both hybrid virus genomes is transcribed into cytoplasmic mRNA during the early phase of Ad2 infection. Hence, we suggest that Ad2 codes for at least one \"early\" gene product which is nonessential for virus growth in cell culture. In both early Ad2+ND1 and Ad2+ND3-infected cells, 1,000 bases of Ad2 DNA adjacent to the integrated SV40 sequences are expressed as cytoplasmic RNA but are not similarly expressed in early Ad2-infected cells. The 3' termini of this early hybrid virus RNA maps in the vicinity of 0.18 on the conventional SV40 map and probably terminates at the same position as early lytic SV40 cytoplasmic RNA. Therefore, the base sequence in this region of SV40 DNA specifies the 3' termini of early messenger RNA present in both hybrid virus and SV40-infected cells."} {"id": "PMID:169393", "title": "Plaque assay of avian sarcoma viruses using casein.", "content": "The caseinolytic activity of several strains of Rous sarcoma virus (RSV), conditional and nonconditional mutants of RSV, and nontransforming avian leukosis viruses was investigated. Only those viruses capable of transforming chick fibroblasts in vitro induced lysis of casein incorporated into an agar overlay. Lysis produced distinct clear areas in the turbid casein-agar gel which allowed a quantitative \"plaque\" assay of cell transformation. Casein plaque formation could not be separated from morphological conversion in cultures infected by wild-type RSV strains. In plates infected by mutants temperature sensitive for transformation, the caseinolytic activity appeared to be affected by temperature to a lesser extent than morphological conversion.", "contents": "Plaque assay of avian sarcoma viruses using casein. The caseinolytic activity of several strains of Rous sarcoma virus (RSV), conditional and nonconditional mutants of RSV, and nontransforming avian leukosis viruses was investigated. Only those viruses capable of transforming chick fibroblasts in vitro induced lysis of casein incorporated into an agar overlay. Lysis produced distinct clear areas in the turbid casein-agar gel which allowed a quantitative \"plaque\" assay of cell transformation. Casein plaque formation could not be separated from morphological conversion in cultures infected by wild-type RSV strains. In plates infected by mutants temperature sensitive for transformation, the caseinolytic activity appeared to be affected by temperature to a lesser extent than morphological conversion."} {"id": "PMID:169394", "title": "Denaturation map of polyoma DNA.", "content": "A denaturation map of polyoma DNA cleaved by Eco R1 to form linear molecules was established by electron microscopy. Partial denaturation, under the same conditions, of fragments obtained by Haemophilus influenzae restriction enzymes allowed us to align the denaturation map with the already established physical map of polyoma DNA (Griffin et al., 1974).", "contents": "Denaturation map of polyoma DNA. A denaturation map of polyoma DNA cleaved by Eco R1 to form linear molecules was established by electron microscopy. Partial denaturation, under the same conditions, of fragments obtained by Haemophilus influenzae restriction enzymes allowed us to align the denaturation map with the already established physical map of polyoma DNA (Griffin et al., 1974)."} {"id": "PMID:169395", "title": "Polyadenylic acid sequences in rhinovirus RNA species from infected human diploid cells.", "content": "Polyadenylic acid sequences were shown to be present in rhinovirus virion RNA. Virus-specified RNA from human embryo lung cells infected with rhinovirus also contained polyadenylic acid but did not contain any polyuridylic acid sequences.", "contents": "Polyadenylic acid sequences in rhinovirus RNA species from infected human diploid cells. Polyadenylic acid sequences were shown to be present in rhinovirus virion RNA. Virus-specified RNA from human embryo lung cells infected with rhinovirus also contained polyadenylic acid but did not contain any polyuridylic acid sequences."} {"id": "PMID:169396", "title": "Base sequence differences between the RNA components of Harvey sarcoma virus.", "content": "The 50 to 70S RNA of the Harvey sarcoma-Moloney leukemia virus (MLV) complex consists of 30 to 40S RNA subunits of two different size classes and contains sequences homologous to Moloney mouse leukemia virus and to information contained in a C-type rat virus, termed NRK virus. We have isolated by preparative gel electrophoresis the large (component 1) and the small (component 2) 30 to 40S RNA species from the Harvey sarcoma-MLV complex. Harvey RNA component 1 was completely complementary to DNA transcribed from MLV RNA and showed no homology to DNA transcribed from NRK virus when annealed under conditions of DNA excess. Harvey RNA component 2 was about 65% complementary to MLV DNA and about 33% complementary to NRK virus DNA. Approximately 60 to 80% of the MLV-specific sequences in RNA component 2 is either a distinct molecular species or is part of a hydrid molecular including NRK virus- and MLV-specific sequences. The rest of the MLV sequences in component 2 could be accounted for by degraded component 1 co-purifying with component 2. The possible role of these sequences in the ability of the virus to transform cells is discussed.", "contents": "Base sequence differences between the RNA components of Harvey sarcoma virus. The 50 to 70S RNA of the Harvey sarcoma-Moloney leukemia virus (MLV) complex consists of 30 to 40S RNA subunits of two different size classes and contains sequences homologous to Moloney mouse leukemia virus and to information contained in a C-type rat virus, termed NRK virus. We have isolated by preparative gel electrophoresis the large (component 1) and the small (component 2) 30 to 40S RNA species from the Harvey sarcoma-MLV complex. Harvey RNA component 1 was completely complementary to DNA transcribed from MLV RNA and showed no homology to DNA transcribed from NRK virus when annealed under conditions of DNA excess. Harvey RNA component 2 was about 65% complementary to MLV DNA and about 33% complementary to NRK virus DNA. Approximately 60 to 80% of the MLV-specific sequences in RNA component 2 is either a distinct molecular species or is part of a hydrid molecular including NRK virus- and MLV-specific sequences. The rest of the MLV sequences in component 2 could be accounted for by degraded component 1 co-purifying with component 2. The possible role of these sequences in the ability of the virus to transform cells is discussed."} {"id": "PMID:169397", "title": "Mapping simian virus 40 mutants by construction of partial heterozygotes.", "content": "Simian virus 40 temperature-sensitive mutants ts A28, A30, B1, B11, and D101 are associated with the region of the genome defined by the restriction endonuclease fragments Hind-I, H, F, G, and E, respectively.", "contents": "Mapping simian virus 40 mutants by construction of partial heterozygotes. Simian virus 40 temperature-sensitive mutants ts A28, A30, B1, B11, and D101 are associated with the region of the genome defined by the restriction endonuclease fragments Hind-I, H, F, G, and E, respectively."} {"id": "PMID:169398", "title": "Mucinous adenocarcinoma of the renal pelvis: discussion of possible pathogenesis.", "content": "A case of mucinous adenocarcinoma of the renal pelvis is reported. The role of infectious agents and the embryologic formation in relation to the malignancy are discussed. Diagnosis of this rare malignancy rests on a high degree of suspicion, coupled with radiologic and cytologic procedures.", "contents": "Mucinous adenocarcinoma of the renal pelvis: discussion of possible pathogenesis. A case of mucinous adenocarcinoma of the renal pelvis is reported. The role of infectious agents and the embryologic formation in relation to the malignancy are discussed. Diagnosis of this rare malignancy rests on a high degree of suspicion, coupled with radiologic and cytologic procedures."} {"id": "PMID:169402", "title": "Acute granulomatous hepatitis. Occurrence in cytomegalovirus mononucleosis.", "content": "Two previously healthy adults with acute granulomatous hepatitis attributable to cytomegalovirus (CMV) monucleosis had prolonged fever, heterophil-negative lymphocytosis with numerous atypical forms, minor alterations in hepatic function, and evidence on biopsy, of a nonspecific acute hepatitis with granulomata. Infection with CMV was corroborated by a rising titer of complement-fixing antibody in case 1 and by a high titer of antibody that later fell in case 2. It is important to exclude CMV ivfection as an etiologic factor in cases of acute granulomatous hepatitis and fever of unknown origin.", "contents": "Acute granulomatous hepatitis. Occurrence in cytomegalovirus mononucleosis. Two previously healthy adults with acute granulomatous hepatitis attributable to cytomegalovirus (CMV) monucleosis had prolonged fever, heterophil-negative lymphocytosis with numerous atypical forms, minor alterations in hepatic function, and evidence on biopsy, of a nonspecific acute hepatitis with granulomata. Infection with CMV was corroborated by a rising titer of complement-fixing antibody in case 1 and by a high titer of antibody that later fell in case 2. It is important to exclude CMV ivfection as an etiologic factor in cases of acute granulomatous hepatitis and fever of unknown origin."} {"id": "PMID:169405", "title": "Xeromammography in early detection of breast cancer.", "content": "Sixty-four carcinomas were detected in 1,315 women examined by xeromammography in 1973. Seventeen carcinomas were occult and 14 were detected in women referred for clinically benign lesions. The remaining 33 carcinomas were diagnosed on the basis of both clinical and roentgenographic examination. There were three false-negatives. Two of these lesions were obscured by very dense fibrocystic disease. The third lesion was called benign due to an error in interpretation. There were eight false-positives; four of these demonstrated intraductal hyperplasia and asymmetry, which may be a precursor to frank malignant change. Xeromammography is suggested as a highly accurate means of detecting occult mammary carcinomas and clarifying the nature of clinically suspected lesions.", "contents": "Xeromammography in early detection of breast cancer. Sixty-four carcinomas were detected in 1,315 women examined by xeromammography in 1973. Seventeen carcinomas were occult and 14 were detected in women referred for clinically benign lesions. The remaining 33 carcinomas were diagnosed on the basis of both clinical and roentgenographic examination. There were three false-negatives. Two of these lesions were obscured by very dense fibrocystic disease. The third lesion was called benign due to an error in interpretation. There were eight false-positives; four of these demonstrated intraductal hyperplasia and asymmetry, which may be a precursor to frank malignant change. Xeromammography is suggested as a highly accurate means of detecting occult mammary carcinomas and clarifying the nature of clinically suspected lesions."} {"id": "PMID:169417", "title": "Complement requirement of neutralizing antibodies in different classes of immunoglobulin appearing in rabbits and guinea pigs after primary and booster immunizations with herpes simplex virus.", "content": "Rabbits and guinea pigs were immunized with herpes simplex virus and bled periodically. The sera were fractionated into slow IgG, fast IgG and IgM by DEAE-cellulose column chromatography, and complement-requiring (CRN) and nonrequiring neutralizing (N) antibody activities were estimated. In early sera of rabbits, the two IgG and IgM fractions possessed about equal CRN activities, although some animals showed a slightly lower activity in fast IgG. In guinea pigs, the early CRN activity resided mainly in slow IgS (7 S gamma2). The early IgG antibody of guinea pigs differed from that of rabbits in that it resembled IgM in resistances to heating at 70 C and to 2-merceptoethanol. The level of CRN IgM antibody in rabbits declined following a peak reached in 2 to 3 weeks, whereas such a decline was never observed in guinea pigs. N IgG antibody was developed a few weeks after the first immunization in rabbits and much retarded in guinea pigs. In both species, booster immunization quickly evoked N antibody in the two IgG fractions and also CRN IgM antibody, but in the case of rabbits the IgM antibody disappeared soon. It is concluded that IgG plays an important role in humoral immunity from the initial stage of the immunization course.", "contents": "Complement requirement of neutralizing antibodies in different classes of immunoglobulin appearing in rabbits and guinea pigs after primary and booster immunizations with herpes simplex virus. Rabbits and guinea pigs were immunized with herpes simplex virus and bled periodically. The sera were fractionated into slow IgG, fast IgG and IgM by DEAE-cellulose column chromatography, and complement-requiring (CRN) and nonrequiring neutralizing (N) antibody activities were estimated. In early sera of rabbits, the two IgG and IgM fractions possessed about equal CRN activities, although some animals showed a slightly lower activity in fast IgG. In guinea pigs, the early CRN activity resided mainly in slow IgS (7 S gamma2). The early IgG antibody of guinea pigs differed from that of rabbits in that it resembled IgM in resistances to heating at 70 C and to 2-merceptoethanol. The level of CRN IgM antibody in rabbits declined following a peak reached in 2 to 3 weeks, whereas such a decline was never observed in guinea pigs. N IgG antibody was developed a few weeks after the first immunization in rabbits and much retarded in guinea pigs. In both species, booster immunization quickly evoked N antibody in the two IgG fractions and also CRN IgM antibody, but in the case of rabbits the IgM antibody disappeared soon. It is concluded that IgG plays an important role in humoral immunity from the initial stage of the immunization course."} {"id": "PMID:169419", "title": "Influence of dialysate calcium concentration and vitamin D on serum parathyroid hormone during repetitive dialysis.", "content": "An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration. The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used. Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments. Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate. No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis. Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml. Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients. After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients. These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis. Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary.", "contents": "Influence of dialysate calcium concentration and vitamin D on serum parathyroid hormone during repetitive dialysis. An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration. The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used. Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments. Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate. No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis. Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml. Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients. After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients. These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis. Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary."} {"id": "PMID:169420", "title": "Renal phosphate reabsorption in the rat: effect of inhibitors.", "content": "The maximum rate of inorganic phosphorus (P1) reabsorption (Tmp1) was measured during phosphate infusion in chronically parathyroidectomized rats. In either initially hydropenic rats or others which underwent moderate preliminary saline loading, Tmp1 tended to rise during early phosphate infusion and then decline, so that steady-state Tmp1 values were similar to the P1 reabsorption rates at the animals' own evelated endogenous plasma P1 concentrations. These results indicate that the \"self-depression\" of Tmp1 during phosphate infusion is not dependent upon the progressive stimulation of endogenous parathyroid hormone secretion. Parathyroid hormone and dibutyryl cyclic adenosine monophosphate (AMP) decreased Tmp1 substantially, whereas acetazolamide inhibited P1 reabsorption at lower filtered P1 loads but did not diminish Tmp1.", "contents": "Renal phosphate reabsorption in the rat: effect of inhibitors. The maximum rate of inorganic phosphorus (P1) reabsorption (Tmp1) was measured during phosphate infusion in chronically parathyroidectomized rats. In either initially hydropenic rats or others which underwent moderate preliminary saline loading, Tmp1 tended to rise during early phosphate infusion and then decline, so that steady-state Tmp1 values were similar to the P1 reabsorption rates at the animals' own evelated endogenous plasma P1 concentrations. These results indicate that the \"self-depression\" of Tmp1 during phosphate infusion is not dependent upon the progressive stimulation of endogenous parathyroid hormone secretion. Parathyroid hormone and dibutyryl cyclic adenosine monophosphate (AMP) decreased Tmp1 substantially, whereas acetazolamide inhibited P1 reabsorption at lower filtered P1 loads but did not diminish Tmp1."} {"id": "PMID:169433", "title": "[The requirements of vitamin D (cholecalciferol) and of 25-hydrocalciferol (25HCC) in premature children during their early life (author's transl)].", "content": "The necessary daily amount of vitamin D3 in premature infants was calculated by H\u00f6vels and his group as being 25 mcg (1000 I.U.). This was in agreement with our own investigations. Without vitamin D3, however, the incidence of rikkets in premature and small-for-dates newborns occurred usually at the beginning of the second month of life. Clinical signs of rickets are still absent at this time, while an increased activity of the serum alkaline phosphatase signals the beginning of the illness. Three groups of prematurely born infants received up to 50 days daily oral doses of 12.5 mcg vitamin D3 (=500 I.U.), 25 mcg vitamin D3 (=1000 I.U.) or 9 mcg 25-hydroxycholecalciferol (25-HCC), respectively, while one untreated group served as control. No differences were noted between the four groups in the serum values of calcium and phosphorus. The activity of the alkaline phosphatase tended to be higher in the untreated and the 500 I.U. groups. The differences were prouved by the chi2-test to be significant (see table 2 and 3). It appeared that 9 mcg of 25-HCC prevented the rise in alkaline phosphatase slightly better than 25 mcg of vitamin D3 (1000 I.U.). On a mcg base 25-HCC seems three times as effective as cholecalciferol. One could speculate about a delayed hydroxylation of cholecalciferol (vitamin D3) to 25-HCC.", "contents": "[The requirements of vitamin D (cholecalciferol) and of 25-hydrocalciferol (25HCC) in premature children during their early life (author's transl)]. The necessary daily amount of vitamin D3 in premature infants was calculated by H\u00f6vels and his group as being 25 mcg (1000 I.U.). This was in agreement with our own investigations. Without vitamin D3, however, the incidence of rikkets in premature and small-for-dates newborns occurred usually at the beginning of the second month of life. Clinical signs of rickets are still absent at this time, while an increased activity of the serum alkaline phosphatase signals the beginning of the illness. Three groups of prematurely born infants received up to 50 days daily oral doses of 12.5 mcg vitamin D3 (=500 I.U.), 25 mcg vitamin D3 (=1000 I.U.) or 9 mcg 25-hydroxycholecalciferol (25-HCC), respectively, while one untreated group served as control. No differences were noted between the four groups in the serum values of calcium and phosphorus. The activity of the alkaline phosphatase tended to be higher in the untreated and the 500 I.U. groups. The differences were prouved by the chi2-test to be significant (see table 2 and 3). It appeared that 9 mcg of 25-HCC prevented the rise in alkaline phosphatase slightly better than 25 mcg of vitamin D3 (1000 I.U.). On a mcg base 25-HCC seems three times as effective as cholecalciferol. One could speculate about a delayed hydroxylation of cholecalciferol (vitamin D3) to 25-HCC."} {"id": "PMID:169435", "title": "Synthesis of type I collagen by human smooth muscle cells in vitro.", "content": "Human vascular smooth muscle cells, derived from explants of medial smooth muscle of a fetal aorta, were grown in vitro and examined with phase and electron microscopy for characteristic morphologic features of smooth muscle cells and for the biosynthesis of connective tissue proteins. Their patterns of growth and ultrastructure were similar to those described for other species of cultured arterial smooth muscle cells. Most cells contained varying amounts of myofilaments interpersed with dense bodies, rough and smooth endoplasmic reticulum, mitochondria, various sized vesicles, lysosomes, and lipid droplets. Extracellularly, small amounts of electron-dense material and microfilaments were observed adjacent to or between the cells. The over-all morphology suggested that the smooth muscle cells were actively engaged in protein synthesis. Although we could not identify banded collagen fibrils in 10- to 14-day-old cultures by electron microscopy, the cells synthesized and secreted a collagen characterized as type I collagen. A hydroxyproline-containing protein composed of two alpha-1 and one alpha-2 chains was extracted from the cell layer. The triple helical precursor of type I collagen, procollagen, was secreted into the medium.", "contents": "Synthesis of type I collagen by human smooth muscle cells in vitro. Human vascular smooth muscle cells, derived from explants of medial smooth muscle of a fetal aorta, were grown in vitro and examined with phase and electron microscopy for characteristic morphologic features of smooth muscle cells and for the biosynthesis of connective tissue proteins. Their patterns of growth and ultrastructure were similar to those described for other species of cultured arterial smooth muscle cells. Most cells contained varying amounts of myofilaments interpersed with dense bodies, rough and smooth endoplasmic reticulum, mitochondria, various sized vesicles, lysosomes, and lipid droplets. Extracellularly, small amounts of electron-dense material and microfilaments were observed adjacent to or between the cells. The over-all morphology suggested that the smooth muscle cells were actively engaged in protein synthesis. Although we could not identify banded collagen fibrils in 10- to 14-day-old cultures by electron microscopy, the cells synthesized and secreted a collagen characterized as type I collagen. A hydroxyproline-containing protein composed of two alpha-1 and one alpha-2 chains was extracted from the cell layer. The triple helical precursor of type I collagen, procollagen, was secreted into the medium."} {"id": "PMID:169436", "title": "Peroxisome depletion in rat liver during pneumococcal sepsis.", "content": "Biochemical and morphometric analysis reveal that the peroxisomal content of rat liver cells is markedly reduced during pneumococcal sepsis. It is suggested that during some bacterial infections, hepatic synthesis of acute-phase serum proteins occurs at the expense of peroxisomal protein synthesis and results in reduction of the peroxisomal protein pool and number of peroxisomes.", "contents": "Peroxisome depletion in rat liver during pneumococcal sepsis. Biochemical and morphometric analysis reveal that the peroxisomal content of rat liver cells is markedly reduced during pneumococcal sepsis. It is suggested that during some bacterial infections, hepatic synthesis of acute-phase serum proteins occurs at the expense of peroxisomal protein synthesis and results in reduction of the peroxisomal protein pool and number of peroxisomes."} {"id": "PMID:169437", "title": "Cellular membranes and membrane-bound enzymes in vitamin E deficiency. A histochemical, cytochemical, biochemical, and morphologic study of the liver of the Pekin duckling.", "content": "The objective of this investigation was to find out whether vitamin E deficiency, apart from influencing the lipid component of cellular membranes, also influences the protein component. For that purpose a number of membrane-bound enzymes in the liver of the Pekin duckling were histochemically, cytochemically, and biochemically examined. Furthermore, cells, cellular membranes, and protein particles in membranes were morphometrically investigated. Histochemically five membrane-bound enzymes appeared to be stimulated in vitamin E deficiency: 5'-nucleotidase, glucose-6-phosphatase, isocitrate dehydrogenase (NADP), tetrazolium reductase (NADH), and tetrazolium reductase (NADPH). 5'-Nucleotidase and glucose-6-phosphatase were also investigated cytochemically and biochemically. The cytochemical localization of these enzymes was identical in control and vitamin E-deficient ducklings. Biochemically, a stimulation of these two enzymes also could be demonstrated. The increase per milligram of DNA appeared to be largest whereas the increase per milligram of protein, per milligram of phospholipid, and per milligram of RNA was only half of the increase per milligram of DNA. This can be explained by the 30 per cent increase of the cell volume in vitamin E deficiency leading to an increase of protein, phospholipid, and RNA per cell. The thickness of membranes and the diameter of protein particles in membranes were measured in liver parenchymal cells. In vitamin E deficiency the thickness of the outer mitochondrial membrane and the diameter of protein particles in this membrane were smaller whereas the thickness of the endoplasmic reticular membrane was larger. The increase of the activities of mitochondrial and microsomal enzymes and the decrease of the thickness of the outer mitochondrial membrane and of its protein particles are interpreted to be the result of the influence of free radicals on membranes with electron transport functions. The increase of 5'-nucleotidase activity in the plasma membrane is likely to have a different cause; it may be related to the transport of nucleotides across this membrane.", "contents": "Cellular membranes and membrane-bound enzymes in vitamin E deficiency. A histochemical, cytochemical, biochemical, and morphologic study of the liver of the Pekin duckling. The objective of this investigation was to find out whether vitamin E deficiency, apart from influencing the lipid component of cellular membranes, also influences the protein component. For that purpose a number of membrane-bound enzymes in the liver of the Pekin duckling were histochemically, cytochemically, and biochemically examined. Furthermore, cells, cellular membranes, and protein particles in membranes were morphometrically investigated. Histochemically five membrane-bound enzymes appeared to be stimulated in vitamin E deficiency: 5'-nucleotidase, glucose-6-phosphatase, isocitrate dehydrogenase (NADP), tetrazolium reductase (NADH), and tetrazolium reductase (NADPH). 5'-Nucleotidase and glucose-6-phosphatase were also investigated cytochemically and biochemically. The cytochemical localization of these enzymes was identical in control and vitamin E-deficient ducklings. Biochemically, a stimulation of these two enzymes also could be demonstrated. The increase per milligram of DNA appeared to be largest whereas the increase per milligram of protein, per milligram of phospholipid, and per milligram of RNA was only half of the increase per milligram of DNA. This can be explained by the 30 per cent increase of the cell volume in vitamin E deficiency leading to an increase of protein, phospholipid, and RNA per cell. The thickness of membranes and the diameter of protein particles in membranes were measured in liver parenchymal cells. In vitamin E deficiency the thickness of the outer mitochondrial membrane and the diameter of protein particles in this membrane were smaller whereas the thickness of the endoplasmic reticular membrane was larger. The increase of the activities of mitochondrial and microsomal enzymes and the decrease of the thickness of the outer mitochondrial membrane and of its protein particles are interpreted to be the result of the influence of free radicals on membranes with electron transport functions. The increase of 5'-nucleotidase activity in the plasma membrane is likely to have a different cause; it may be related to the transport of nucleotides across this membrane."} {"id": "PMID:169438", "title": "Encephalitis in suckling rats induced with rat cytomegalovirus.", "content": "Encephalitis has been induced in suckling rats by intracerebral inoculation of rat cytomegalovirus. This agent has been carried through five animal passages without changes in virulence. Principal sites of viral attack were the meninges and ependyma with limited parenchymal invasion from these sites. Characteristic features of cytomegalovirus disease observed included cytomegaly, formation of nuclear and cytoplasmic inclusions, and polykaryocytosis. Fundamental tinctorial and optical differences were noted between nuclear and cytoplasmic inclusions, the latter being characterized by their phloxinophilia which contrasts with the hematoxylinophilia of nuclear inclusions. Differential interference microscopy improved visualization and photography of cytoplasmic inclusions. Hydrocephalus developed in a few of the animals and was studied in late phases of the disease.", "contents": "Encephalitis in suckling rats induced with rat cytomegalovirus. Encephalitis has been induced in suckling rats by intracerebral inoculation of rat cytomegalovirus. This agent has been carried through five animal passages without changes in virulence. Principal sites of viral attack were the meninges and ependyma with limited parenchymal invasion from these sites. Characteristic features of cytomegalovirus disease observed included cytomegaly, formation of nuclear and cytoplasmic inclusions, and polykaryocytosis. Fundamental tinctorial and optical differences were noted between nuclear and cytoplasmic inclusions, the latter being characterized by their phloxinophilia which contrasts with the hematoxylinophilia of nuclear inclusions. Differential interference microscopy improved visualization and photography of cytoplasmic inclusions. Hydrocephalus developed in a few of the animals and was studied in late phases of the disease."} {"id": "PMID:169440", "title": "Physiology of the natural polyamines putrescine, spermidine and spermine.", "content": "The biochemistry and biological function of the naturally occurring polyamines, putrescine, spermidine, and spermine, have been reviewed with special reference to animal organisms. These compounds are universally distributed in all living material. Their biosynthesis from ornithine and methionine is accurately controlled and may fluctuate according to the metabolic needs of the cell. Polyamines strongly and specifically interact with nucleic acids in vitro. It appears that under physiological conditions a substantial portion of cellular polyamines is noncovalently bound to nucleic acids and nucleic acid-containing structures such as ribosomes. Polyamines are able to stimulate protein and ribonucleic acid synthesis in vitro. In several systems characterized by rapid growth polyamines and ribonucleic acid accumulate in parrallel. Evidence that polyamines may have an essential role in protein and/or nucleic acid synthesis is substantiated by recent observations on polyamine-deficient bacterial mutants, although no specific function has been established with certainty as yet. Some clinical applications of polyamine research related to cancer are also discussed briefly.", "contents": "Physiology of the natural polyamines putrescine, spermidine and spermine. The biochemistry and biological function of the naturally occurring polyamines, putrescine, spermidine, and spermine, have been reviewed with special reference to animal organisms. These compounds are universally distributed in all living material. Their biosynthesis from ornithine and methionine is accurately controlled and may fluctuate according to the metabolic needs of the cell. Polyamines strongly and specifically interact with nucleic acids in vitro. It appears that under physiological conditions a substantial portion of cellular polyamines is noncovalently bound to nucleic acids and nucleic acid-containing structures such as ribosomes. Polyamines are able to stimulate protein and ribonucleic acid synthesis in vitro. In several systems characterized by rapid growth polyamines and ribonucleic acid accumulate in parrallel. Evidence that polyamines may have an essential role in protein and/or nucleic acid synthesis is substantiated by recent observations on polyamine-deficient bacterial mutants, although no specific function has been established with certainty as yet. Some clinical applications of polyamine research related to cancer are also discussed briefly."} {"id": "PMID:169441", "title": "Loss of epinephrine stimulated synthesis of cyclic adenosine 3':5' monophosphate during maturation of rabbit and human reticulocytes.", "content": "The adenylate cyclase activity of rabbit reticulocytes is localized in the stroma. Rabbit reticulocytes are four times more active than mature erythrocytes in transforming in situ formed [14C] adenosine triphosphate into [14C] cyclic adenosine 3':5'-monophosphate. Similarly, anaemic human red blood cells show higher activity in effecting this transformation. The adenylate cyclase activity is stimulated by epinephrine, 40% in rabbit reticulocytes, and 70-80% in anaemic human RBC but not in erythrocytes. Both the reticulocytes and erythrocytes can bind [14C] epinephrine, but the reticulocytes bind a relatively large amount. A glycogen phosphorylase that can be activated by cyclic adenosine 3':5'-monophosphate is detected only in reticulocytes. Both reticulocytes and erythrocytes contain a phosphodiesterase which can hydrolyse cyclic 3':5'-adenosine monophosphate and which is activated by imidazole and inhibited by methyl xanthines.", "contents": "Loss of epinephrine stimulated synthesis of cyclic adenosine 3':5' monophosphate during maturation of rabbit and human reticulocytes. The adenylate cyclase activity of rabbit reticulocytes is localized in the stroma. Rabbit reticulocytes are four times more active than mature erythrocytes in transforming in situ formed [14C] adenosine triphosphate into [14C] cyclic adenosine 3':5'-monophosphate. Similarly, anaemic human red blood cells show higher activity in effecting this transformation. The adenylate cyclase activity is stimulated by epinephrine, 40% in rabbit reticulocytes, and 70-80% in anaemic human RBC but not in erythrocytes. Both the reticulocytes and erythrocytes can bind [14C] epinephrine, but the reticulocytes bind a relatively large amount. A glycogen phosphorylase that can be activated by cyclic adenosine 3':5'-monophosphate is detected only in reticulocytes. Both reticulocytes and erythrocytes contain a phosphodiesterase which can hydrolyse cyclic 3':5'-adenosine monophosphate and which is activated by imidazole and inhibited by methyl xanthines."} {"id": "PMID:169443", "title": "[A electromyographic study of the vestibular reflexes. A clinical experimental study on human beings (author's transl)].", "content": "It is reported about myography on testpersons with normal vestibular function as well as on patients after operativ dissection of the VIII. nerve, neuropathia nerv. vest. and M. Meni\u00e8re. On the base of these findings it is supposed that myography proofes to be a useful help in the judgement of the specific influence of the vestibular organs on the motoric system. The myographic changes of the muscular activity after caloric stimulation give exact information about the entire vestibular system and especially about the vestibular-spinal-pathways. The best way of testing the vestibular activity is performed on musculars with symmetric, simultaneous and reziproke intented innervation, f.i. on the sternocleidomastoidei muscels in slight deflected position of the head. Most significant for the vestibular influence are an increase of the base-activity and the appearance of groups of potentials which are related to the vestibular stimulus in time and intensity.", "contents": "[A electromyographic study of the vestibular reflexes. A clinical experimental study on human beings (author's transl)]. It is reported about myography on testpersons with normal vestibular function as well as on patients after operativ dissection of the VIII. nerve, neuropathia nerv. vest. and M. Meni\u00e8re. On the base of these findings it is supposed that myography proofes to be a useful help in the judgement of the specific influence of the vestibular organs on the motoric system. The myographic changes of the muscular activity after caloric stimulation give exact information about the entire vestibular system and especially about the vestibular-spinal-pathways. The best way of testing the vestibular activity is performed on musculars with symmetric, simultaneous and reziproke intented innervation, f.i. on the sternocleidomastoidei muscels in slight deflected position of the head. Most significant for the vestibular influence are an increase of the base-activity and the appearance of groups of potentials which are related to the vestibular stimulus in time and intensity."} {"id": "PMID:169444", "title": "Neurologic implications of glomus tumors in the head and neck.", "content": "Seventy-six patients with glomus tumors were evaluated. The incidenc- of cranial nerve paralysis in 37 percent and the incidence of intracranial extension is 14.6 percent. Jugular foramen syndrome is associated with 50 percent, and hypoglossal nerve involvement with 75 percent incidence of posterior fossa extension. Horner's syndrome is associated with 50 percent of middle cranial fossa invasion. The incidence of CNS tumor involvement with cranial nerve paralysis (not including VIIth nerve) is 52 percent.", "contents": "Neurologic implications of glomus tumors in the head and neck. Seventy-six patients with glomus tumors were evaluated. The incidenc- of cranial nerve paralysis in 37 percent and the incidence of intracranial extension is 14.6 percent. Jugular foramen syndrome is associated with 50 percent, and hypoglossal nerve involvement with 75 percent incidence of posterior fossa extension. Horner's syndrome is associated with 50 percent of middle cranial fossa invasion. The incidence of CNS tumor involvement with cranial nerve paralysis (not including VIIth nerve) is 52 percent."} {"id": "PMID:169452", "title": "Role of cytidine triphosphate and cytidine diphosphate in promoting inositol entry into microsomal phosphatidylinositol.", "content": "The Mn2+ activated incorporation of myo-inositol-3H into subfractions of phosphatidylinositol in rat liver microsomes was studied in the presence and absence of cytidine triphosphate or cytidine diphosphate choline using phosphate buffer. The distribution of labeled inositol among molecular species of microsomal phosphatidylinositol was also investigated in vivo. In other experiments, the release of radioactivity from microsomes labeled with inositol-3H in the phospholipid was measured after the addition of Mn2+, unlabeled inositol, and cytidine nucleotide. Similar chase experiments were conducted with microsomes containing phosphatidylcholine-14C or phosphatidylethanolamine-14C. The addition of cytidine triphosphate or cytidine diphosphate choline stimulated the rate of inositol-3H entry into microsomal phosphatidylinositol by 3.5 to 4-fold and the monoenoic plus dienoic, trienoic, tetraenoic, and polyenoic species contained 6-7, 6, 78-81, and 7-9%, of radioactivity, respectively. These latter patterns were very similar to those observed among the corresponding molecular species when the Mn2+ stimulated entry of free inositol into phospholipid was studied in the absence of added cytidine nucleotide. In chase experiments, the release of radioactivity from phospholipid in the presence of cytidine trephosphate or cytidine diphosphate choline was greatly enhanced by the addition of free inositol when microsomes containing phosphatidylinositol-3H, but not phosphatidylcholine-14C or phosphatidylethanolamine-14C, were employed. Therefore, under the present conditions, cytidine triphosphate and cytidine diphosphate choline appear to stimulate the entry of inositol into phosphatidylinositol by enhancing the Mn2+ activated exchange reaction in rat liver microsomes. The results suggest further that phosphatidylinositol is the preferred substrate when this reaction is stimulated by cytidine nucleotide.", "contents": "Role of cytidine triphosphate and cytidine diphosphate in promoting inositol entry into microsomal phosphatidylinositol. The Mn2+ activated incorporation of myo-inositol-3H into subfractions of phosphatidylinositol in rat liver microsomes was studied in the presence and absence of cytidine triphosphate or cytidine diphosphate choline using phosphate buffer. The distribution of labeled inositol among molecular species of microsomal phosphatidylinositol was also investigated in vivo. In other experiments, the release of radioactivity from microsomes labeled with inositol-3H in the phospholipid was measured after the addition of Mn2+, unlabeled inositol, and cytidine nucleotide. Similar chase experiments were conducted with microsomes containing phosphatidylcholine-14C or phosphatidylethanolamine-14C. The addition of cytidine triphosphate or cytidine diphosphate choline stimulated the rate of inositol-3H entry into microsomal phosphatidylinositol by 3.5 to 4-fold and the monoenoic plus dienoic, trienoic, tetraenoic, and polyenoic species contained 6-7, 6, 78-81, and 7-9%, of radioactivity, respectively. These latter patterns were very similar to those observed among the corresponding molecular species when the Mn2+ stimulated entry of free inositol into phospholipid was studied in the absence of added cytidine nucleotide. In chase experiments, the release of radioactivity from phospholipid in the presence of cytidine trephosphate or cytidine diphosphate choline was greatly enhanced by the addition of free inositol when microsomes containing phosphatidylinositol-3H, but not phosphatidylcholine-14C or phosphatidylethanolamine-14C, were employed. Therefore, under the present conditions, cytidine triphosphate and cytidine diphosphate choline appear to stimulate the entry of inositol into phosphatidylinositol by enhancing the Mn2+ activated exchange reaction in rat liver microsomes. The results suggest further that phosphatidylinositol is the preferred substrate when this reaction is stimulated by cytidine nucleotide."} {"id": "PMID:169459", "title": "Japanese encephalitis in an Australian soldier returned from Vietnam.", "content": "An imported case of Japanese encephalitis is reported and discussed. Recent literature on the clinical aspects of the disease is reviewed. Although the disease is unlikely to become a problem in Australia, it will remain a serious hazard to nonimmune personnel moving into an endemic area.", "contents": "Japanese encephalitis in an Australian soldier returned from Vietnam. An imported case of Japanese encephalitis is reported and discussed. Recent literature on the clinical aspects of the disease is reviewed. Although the disease is unlikely to become a problem in Australia, it will remain a serious hazard to nonimmune personnel moving into an endemic area."} {"id": "PMID:169455", "title": "[Composition and content of cytochromes in Rhodopseudomonas palustris in relation to growth conditions].", "content": "Differential spectra, CO spectra and spectra of hemochromes were studied in the cells of Rhodopseudomonas palustris grown in aerobic conditions in the light and in the darkness; the terminal oxidase was cytochrome a. This cytochrome was not detected in the cells cultivated in anaerobic conditions in the light. The content of cytochromes b was higher in the cells grown in aerobic conditions in the darkness; the content of cytochromes c was higher in the cells cultivated in anaerobic conditions in the light.", "contents": "[Composition and content of cytochromes in Rhodopseudomonas palustris in relation to growth conditions]. Differential spectra, CO spectra and spectra of hemochromes were studied in the cells of Rhodopseudomonas palustris grown in aerobic conditions in the light and in the darkness; the terminal oxidase was cytochrome a. This cytochrome was not detected in the cells cultivated in anaerobic conditions in the light. The content of cytochromes b was higher in the cells grown in aerobic conditions in the darkness; the content of cytochromes c was higher in the cells cultivated in anaerobic conditions in the light."} {"id": "PMID:169457", "title": "[Function of cytochrome c in a mutant of Candida mycoderma yeasts lacking in cytochromes b and a+a3].", "content": "The mutant of Candida mycoderma was studied, which lacked cytochromes b and a+a3. The mutant contained only cytochrome c which functioned with cytochrome c peroxidase in the absence of any cytochrome c oxidases.", "contents": "[Function of cytochrome c in a mutant of Candida mycoderma yeasts lacking in cytochromes b and a+a3]. The mutant of Candida mycoderma was studied, which lacked cytochromes b and a+a3. The mutant contained only cytochrome c which functioned with cytochrome c peroxidase in the absence of any cytochrome c oxidases."} {"id": "PMID:169456", "title": "[NAD-dependent N-methylglutamate dehydrogenase--new enzyme metabolizing methylamine in methylotrophs].", "content": "The properties of N-methylglutamate dehydrogenase, a new enzyme of methylamine metabolism in a facultative methylotroph Pseudomonas methylica, strain 2, were investigated. The enzyme was strictly dependent on the NAD presence and was not connected with particles in cell-free preparations. The enzyme appeared to be incucible and its activity increased after the growth of the cells in a medium containing methylamine.", "contents": "[NAD-dependent N-methylglutamate dehydrogenase--new enzyme metabolizing methylamine in methylotrophs]. The properties of N-methylglutamate dehydrogenase, a new enzyme of methylamine metabolism in a facultative methylotroph Pseudomonas methylica, strain 2, were investigated. The enzyme was strictly dependent on the NAD presence and was not connected with particles in cell-free preparations. The enzyme appeared to be incucible and its activity increased after the growth of the cells in a medium containing methylamine."} {"id": "PMID:169464", "title": "In vitro repair of UV-or x-irradiated bacteriophage T4 DNA by extract from blue-green alga Anacystis nidulans.", "content": "The cell-free extract from blue-green alga Anacystis nidulans contains enzymatic activities which repair in vitro transforming DNA of bacteriophage T4 damaged by UV light or X-rays. The repair effect of the extract was observed with double-stranded irradiated DNA but not with denatured irradiated DNA. The level of restoration of the transforming activity depends on the protein concentration in the reaction mixture and on the dose of irradiation. A fraction of DNA lesions induced by X-rays is repaired by a NAD-dependent polynucleotide ligase present in the extract. The repair of UV-induced lesions is the most efficient in the presence of magnesium ions, NAD, ATP and the four deoxynucleoside triphosphates. The results indicate that the repair of UV-irradiated DNA is performed with the participation of DNA polymerase and polynucleotide ligase which function in the cell-free extract of the algae on the background of a low deoxyribonuclease activity.", "contents": "In vitro repair of UV-or x-irradiated bacteriophage T4 DNA by extract from blue-green alga Anacystis nidulans. The cell-free extract from blue-green alga Anacystis nidulans contains enzymatic activities which repair in vitro transforming DNA of bacteriophage T4 damaged by UV light or X-rays. The repair effect of the extract was observed with double-stranded irradiated DNA but not with denatured irradiated DNA. The level of restoration of the transforming activity depends on the protein concentration in the reaction mixture and on the dose of irradiation. A fraction of DNA lesions induced by X-rays is repaired by a NAD-dependent polynucleotide ligase present in the extract. The repair of UV-induced lesions is the most efficient in the presence of magnesium ions, NAD, ATP and the four deoxynucleoside triphosphates. The results indicate that the repair of UV-irradiated DNA is performed with the participation of DNA polymerase and polynucleotide ligase which function in the cell-free extract of the algae on the background of a low deoxyribonuclease activity."} {"id": "PMID:169465", "title": "[Translation of hormone receptor interactions into biological function. A hypothesis (author's transl)].", "content": "Published data revealing discrepancies between the kinetics of hormone binding and adenylate cyclase activation are critically analyzed. This analysis gave rise to the hypothesis concerning the translation of hormone receptor interactions into biological function, i.e.: adenylate cyclase activation. Because the lifetime of the hormone receptor complex is too long, other steps in signal transfer are considered for the control of adenylate cyclase activity.", "contents": "[Translation of hormone receptor interactions into biological function. A hypothesis (author's transl)]. Published data revealing discrepancies between the kinetics of hormone binding and adenylate cyclase activation are critically analyzed. This analysis gave rise to the hypothesis concerning the translation of hormone receptor interactions into biological function, i.e.: adenylate cyclase activation. Because the lifetime of the hormone receptor complex is too long, other steps in signal transfer are considered for the control of adenylate cyclase activity."} {"id": "PMID:169466", "title": "Sinusitis of the maxillary antrum.", "content": "Twenty-four adults with clinical evidence of sinusitis were studied by 65 needle punctures of the maxillary antrum. Fourteen of 15 sinuses with normal transillumination and 19 of 26 that were dull had normal aspirates, whereas 24 of 24 that were opaque had abnormal aspirates (P less than 0.001). Marked mucosal thickening as determined radiologically (Water's view) was associated with abnormal aspirates whereas lesser mucosal thickening was not (P less than 0.001). In acute sinusitis, there was a strong correlation between high aspirate leukocyte counts (greater than 1000 per cubic millimeter) and infection as manifested by bacterial titers of greater than 10(5) per milliliter or the isolation of virus fungus (P greater than 0.001). Anterior-nasal-swab cultures correlated poorly with direct aspirate culters. Organisms frequently recovered from the sinus included Haemophilus influenzae, Strepto coccus pneumoniae, and anaerobic bacteria. Rhinovirus was recovered twice. Antibiotics were usedful in patients with acute sinusitis if the organism was sensitive in vitro (P less than 0.001).", "contents": "Sinusitis of the maxillary antrum. Twenty-four adults with clinical evidence of sinusitis were studied by 65 needle punctures of the maxillary antrum. Fourteen of 15 sinuses with normal transillumination and 19 of 26 that were dull had normal aspirates, whereas 24 of 24 that were opaque had abnormal aspirates (P less than 0.001). Marked mucosal thickening as determined radiologically (Water's view) was associated with abnormal aspirates whereas lesser mucosal thickening was not (P less than 0.001). In acute sinusitis, there was a strong correlation between high aspirate leukocyte counts (greater than 1000 per cubic millimeter) and infection as manifested by bacterial titers of greater than 10(5) per milliliter or the isolation of virus fungus (P greater than 0.001). Anterior-nasal-swab cultures correlated poorly with direct aspirate culters. Organisms frequently recovered from the sinus included Haemophilus influenzae, Strepto coccus pneumoniae, and anaerobic bacteria. Rhinovirus was recovered twice. Antibiotics were usedful in patients with acute sinusitis if the organism was sensitive in vitro (P less than 0.001)."} {"id": "PMID:169471", "title": "How specific are nuclear \"receptors\" for thyroid hormones?", "content": "The presence of \"high-affinity-saturable\" binding sites for thyroid hormones of similar characteristics not only in isolated nuclei but in all the major extranuclear cellular components, as well as the failure of cytosol to promote nuclear binding, invalidates the analogy with steroid hormone receptors and necessitates a more critical assessment of the physiological relevance of current approaches to binding of thyroid hormone in vitro nuclear preparations.", "contents": "How specific are nuclear \"receptors\" for thyroid hormones? The presence of \"high-affinity-saturable\" binding sites for thyroid hormones of similar characteristics not only in isolated nuclei but in all the major extranuclear cellular components, as well as the failure of cytosol to promote nuclear binding, invalidates the analogy with steroid hormone receptors and necessitates a more critical assessment of the physiological relevance of current approaches to binding of thyroid hormone in vitro nuclear preparations."} {"id": "PMID:169474", "title": "Is the evolution of insulin Darwinian or due to selectively neutral mutation?", "content": "A model for the evolution of insulin mainly in terms of adaptive processes is discussed. The model depends critically on the relationship of sequence changes to the three-dimensional structure and the role of various parts of this structure in the conversion of the proinsulin molecule to the active form, the storage of insulin, its transport to the site of action and its interaction with a receptor.", "contents": "Is the evolution of insulin Darwinian or due to selectively neutral mutation? A model for the evolution of insulin mainly in terms of adaptive processes is discussed. The model depends critically on the relationship of sequence changes to the three-dimensional structure and the role of various parts of this structure in the conversion of the proinsulin molecule to the active form, the storage of insulin, its transport to the site of action and its interaction with a receptor."} {"id": "PMID:169480", "title": "Dopamine- and apomorphine-sensitive adenylate cyclase in homogenates of rabbit retina.", "content": "Dopamine (0.5-100 muM) as well as apomorphine (1-100 muM) were found to be potent stimulators of adenylate cyclase in homogenates of rabbit retina. When compared with the dopamine-effect at 10 muM, half-stimulation was also obtained in response to noradrenaline or adrenaline, whereas isoprenaline or phenylephrine were ineffective. Furthermore, the dopamine-induced production of cyclic AMP wab blocked by chloropromazine and haloperidol. These data would suggest the occurrence of a specific \"dopamine receptor\" in the retina of the rabbit.", "contents": "Dopamine- and apomorphine-sensitive adenylate cyclase in homogenates of rabbit retina. Dopamine (0.5-100 muM) as well as apomorphine (1-100 muM) were found to be potent stimulators of adenylate cyclase in homogenates of rabbit retina. When compared with the dopamine-effect at 10 muM, half-stimulation was also obtained in response to noradrenaline or adrenaline, whereas isoprenaline or phenylephrine were ineffective. Furthermore, the dopamine-induced production of cyclic AMP wab blocked by chloropromazine and haloperidol. These data would suggest the occurrence of a specific \"dopamine receptor\" in the retina of the rabbit."} {"id": "PMID:169481", "title": "Glucose-6-phosphatase (EC 3.1.3.9) and esterase (EC 3.1.1.1) activities of microsomes prepared from perfused rat livers after partial outflow block or phalloidin poisoning.", "content": "Microsomes were prepared from perfused rat livers after different perfusion procedures. The yield of microsomal protein and the kinetic data (Km, Vmax) of glucose-6-phosphatase (3.1.3.9) and esterase (3.1.1.1) activities were analysed in each preparation. No marked differences were detected between conventionally prepared liver microsomes and those from livers perfused 1 hr with an erythrocytes-free medium under the conditions of open outflow. If the outflow pressure was increased artificially, the yield of microsomal protein decreased. The Vmax of both enzymes was markedly increased, whereas the Km values remained unchanged. The same microsomal alterations occurred when perfused rat livers were poisoned with phalloidin in vitro under the condition of open outflow. Our findings indicate that microsomal alterations in livers from poisoned animals might be due to microcirculatory disturbances, and not primary effects of the toxin on the endoplasmatic reticulum.", "contents": "Glucose-6-phosphatase (EC 3.1.3.9) and esterase (EC 3.1.1.1) activities of microsomes prepared from perfused rat livers after partial outflow block or phalloidin poisoning. Microsomes were prepared from perfused rat livers after different perfusion procedures. The yield of microsomal protein and the kinetic data (Km, Vmax) of glucose-6-phosphatase (3.1.3.9) and esterase (3.1.1.1) activities were analysed in each preparation. No marked differences were detected between conventionally prepared liver microsomes and those from livers perfused 1 hr with an erythrocytes-free medium under the conditions of open outflow. If the outflow pressure was increased artificially, the yield of microsomal protein decreased. The Vmax of both enzymes was markedly increased, whereas the Km values remained unchanged. The same microsomal alterations occurred when perfused rat livers were poisoned with phalloidin in vitro under the condition of open outflow. Our findings indicate that microsomal alterations in livers from poisoned animals might be due to microcirculatory disturbances, and not primary effects of the toxin on the endoplasmatic reticulum."} {"id": "PMID:169482", "title": "Adenylate cyclase and phosphodiesterase in the rat gastric mucosa after starvation, feeding and pentagastrin.", "content": "The effects of starvation, feeding and pentagastrin on gastric mucosal adenylate cyclase (AC) and phosphodiesterase (PDE) activity were studied in the rat. 1. Starvation for 24 hrs and 48 hrs reduced both NaF stimulated and basal AC activities. 2. Feeding of starved rats slowly raised the AC activity up to 430% within 4 hrs after feeding. This effect was more pronounced under basal conditions than with NaF stimulation. 3. A single i.p. injection of pentagastrin (125 mug/kg) caused a stimulation of basal AC lasting 45 min, which was followed by a subsequent decrease in the basal and NaF stimulated enzyme activity. 4. PDE activity was not influenced by starvation and feeding but underwent a transient inhibition by pentagastrin. Accordingly gastric mucosal cAMP levels after starvation, feeding and pentagastrin are regulated by changes in AC and not in PDE activity. The rise in AC activity after feeding appears to be related to functions other than H+ and pepsin secretion.", "contents": "Adenylate cyclase and phosphodiesterase in the rat gastric mucosa after starvation, feeding and pentagastrin. The effects of starvation, feeding and pentagastrin on gastric mucosal adenylate cyclase (AC) and phosphodiesterase (PDE) activity were studied in the rat. 1. Starvation for 24 hrs and 48 hrs reduced both NaF stimulated and basal AC activities. 2. Feeding of starved rats slowly raised the AC activity up to 430% within 4 hrs after feeding. This effect was more pronounced under basal conditions than with NaF stimulation. 3. A single i.p. injection of pentagastrin (125 mug/kg) caused a stimulation of basal AC lasting 45 min, which was followed by a subsequent decrease in the basal and NaF stimulated enzyme activity. 4. PDE activity was not influenced by starvation and feeding but underwent a transient inhibition by pentagastrin. Accordingly gastric mucosal cAMP levels after starvation, feeding and pentagastrin are regulated by changes in AC and not in PDE activity. The rise in AC activity after feeding appears to be related to functions other than H+ and pepsin secretion."} {"id": "PMID:169483", "title": "Comparative effects of adenosine and adenine and guanine nucleotides on drug biotransformation in rats.", "content": "The effect of various nucleotides and adenosine on the hepatic biotransformation of hexobarbital sodium (HB) and p-chloro-N-methylaniline (PCMA) was determined in male rats. Intraperitoneal administration of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), alone and in combination with theophylline, and the cyclic adenosine 3',5'-monophosphate (cAMP)-theophylline combination prolonged HB sleeping time by more than 70%. cAMP or dibutyryl cyclic guanosine 3',5'-monophosphate (DBcGMP), alone or in combination with theophylline, failed to significantly alter the duration of HB-induced hypnosis. Plasma levels of HB upon awakening suggested that the increase in sleeping time was apparently not due to an altered sensitivity of the brain to the barbiturate. The effect appears to be related to an impairment of HB metabolism since only those compounds that inhibited HB oxidation when added to liver slices prolonged hypnosis. In addition, 5'-AMP, adenosine, and cyclic guanosine 3',5'-monophosphate (cGMP) failed to alter HB biotransformation by liver slices. A similar pattern of impairment of metabolism by liver slices was observed when PCMA was used as the substrate. The inhibitory effect of DBcAMP was not altered by concurrent addition of either cGMP or DBcGMP. No impairment in the rate of microsomal PCMA biotransformation resulted from addition of adenosine or any of the nucleotides used in this study.", "contents": "Comparative effects of adenosine and adenine and guanine nucleotides on drug biotransformation in rats. The effect of various nucleotides and adenosine on the hepatic biotransformation of hexobarbital sodium (HB) and p-chloro-N-methylaniline (PCMA) was determined in male rats. Intraperitoneal administration of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), alone and in combination with theophylline, and the cyclic adenosine 3',5'-monophosphate (cAMP)-theophylline combination prolonged HB sleeping time by more than 70%. cAMP or dibutyryl cyclic guanosine 3',5'-monophosphate (DBcGMP), alone or in combination with theophylline, failed to significantly alter the duration of HB-induced hypnosis. Plasma levels of HB upon awakening suggested that the increase in sleeping time was apparently not due to an altered sensitivity of the brain to the barbiturate. The effect appears to be related to an impairment of HB metabolism since only those compounds that inhibited HB oxidation when added to liver slices prolonged hypnosis. In addition, 5'-AMP, adenosine, and cyclic guanosine 3',5'-monophosphate (cGMP) failed to alter HB biotransformation by liver slices. A similar pattern of impairment of metabolism by liver slices was observed when PCMA was used as the substrate. The inhibitory effect of DBcAMP was not altered by concurrent addition of either cGMP or DBcGMP. No impairment in the rate of microsomal PCMA biotransformation resulted from addition of adenosine or any of the nucleotides used in this study."} {"id": "PMID:169484", "title": "Pre- and post-junctional receptor-mediated cholinergic interactions with adrenergic transmission in guinea-pig vas deferens.", "content": "Isolated, superfused, field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline, was used to study the interaction between exogenous and endogenous acetylcholine and adrenergic neuroeffector function. Exogenous acetylcholine was found to exert a dual muscarinic effect on the preparation, consisting of depression of the secretion of tracer noradrenaline from the sympathetic nerves, as well as enhancement of the nerve stimulation-induced contraction of the preparation. The results indicate that endogenous acetylcholine may play an analogous role, since eserine enhanced the nerve stimulation-induced contraction, without markedly affecting the secretion of labelled noradrenaline (the effect was abolished by atropine), while higher concentrations of atropine depressed the contraction and actually enhanced the secretion of labelled noradrenaline. The findings support the concept that guinea-pig vas deferens has a dual, cholinergic as well as adrenergic, innervation, and that the cholinergic nerves exert a dual modulatory effect on sympathetic neuro-effector function in this tissue: Firstly they appear to restrict the secretion of sympathetic neurotransmitter (via pre-junctional muscarinic receptors, on the adrenergic nerve terminals), and secondly they seem to enhance the excitability of the smooth muscle to sympathetic neurotransmitter (via post-junctional muscarinic receptors, on the smooth muscle cells).", "contents": "Pre- and post-junctional receptor-mediated cholinergic interactions with adrenergic transmission in guinea-pig vas deferens. Isolated, superfused, field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline, was used to study the interaction between exogenous and endogenous acetylcholine and adrenergic neuroeffector function. Exogenous acetylcholine was found to exert a dual muscarinic effect on the preparation, consisting of depression of the secretion of tracer noradrenaline from the sympathetic nerves, as well as enhancement of the nerve stimulation-induced contraction of the preparation. The results indicate that endogenous acetylcholine may play an analogous role, since eserine enhanced the nerve stimulation-induced contraction, without markedly affecting the secretion of labelled noradrenaline (the effect was abolished by atropine), while higher concentrations of atropine depressed the contraction and actually enhanced the secretion of labelled noradrenaline. The findings support the concept that guinea-pig vas deferens has a dual, cholinergic as well as adrenergic, innervation, and that the cholinergic nerves exert a dual modulatory effect on sympathetic neuro-effector function in this tissue: Firstly they appear to restrict the secretion of sympathetic neurotransmitter (via pre-junctional muscarinic receptors, on the adrenergic nerve terminals), and secondly they seem to enhance the excitability of the smooth muscle to sympathetic neurotransmitter (via post-junctional muscarinic receptors, on the smooth muscle cells)."} {"id": "PMID:169485", "title": "Effects of 6-hydroxydopamine Treatment at birth on the submaxillary gland of the rat.", "content": "Six and 18 months after neonatal administration of 6-hydroxy-dopamine or surgical sympathetic denervation the submaxillary gland of the rat showed a marked depletion of noradrenaline stores. Six months afer removal of the superior cervical ganglion the gland's endogenous noradrenaline was lowered to 0.032 +/- 0.004 mug/g while after neonatal 6-hydroxydopamine the values were 0.228 +/- 0.023 mug/g (controls 2.145 +/- 0.382 mug/g). Eighteen months after either type of sympathetic denervation the neurotransmitter was still depleted. In rats treated with 6-hydroxydopamine the sailagogue effect of injected noradrenaline was potentiated 2.7-fold while the potentiation of the effect of noradrenaline was 3.6 times after surgical denervation. The magnitude of the supersensitivity developed to isoprenaline did not differ between both types of denervation. No supersensitivity to the cholinomimetic agent, methacholine, was observed. Cocaine administration or removal of the superior cervical ganglion slightly increased the supersensivity to noradrenaline in rats treated with 6-hydroxydopamine. Eighteen months after surgical or chemical denervation, the activity of choline-acetyl-transferase in the submaxillary gland was increased by about 50%. Of the respiratory enzymes studied, sussinic dehydrogenase, fumarase and cytochrome oxidase, the activity of only the latter was markedly reduced by a chronic sympathetic denervation. From the results obtained it is concluded that neonatal treatment with 6-hydroxy-dopamine causes a permanent and almost complete sympathectomy of the submaxillary gland of the rat.", "contents": "Effects of 6-hydroxydopamine Treatment at birth on the submaxillary gland of the rat. Six and 18 months after neonatal administration of 6-hydroxy-dopamine or surgical sympathetic denervation the submaxillary gland of the rat showed a marked depletion of noradrenaline stores. Six months afer removal of the superior cervical ganglion the gland's endogenous noradrenaline was lowered to 0.032 +/- 0.004 mug/g while after neonatal 6-hydroxydopamine the values were 0.228 +/- 0.023 mug/g (controls 2.145 +/- 0.382 mug/g). Eighteen months after either type of sympathetic denervation the neurotransmitter was still depleted. In rats treated with 6-hydroxydopamine the sailagogue effect of injected noradrenaline was potentiated 2.7-fold while the potentiation of the effect of noradrenaline was 3.6 times after surgical denervation. The magnitude of the supersensitivity developed to isoprenaline did not differ between both types of denervation. No supersensitivity to the cholinomimetic agent, methacholine, was observed. Cocaine administration or removal of the superior cervical ganglion slightly increased the supersensivity to noradrenaline in rats treated with 6-hydroxydopamine. Eighteen months after surgical or chemical denervation, the activity of choline-acetyl-transferase in the submaxillary gland was increased by about 50%. Of the respiratory enzymes studied, sussinic dehydrogenase, fumarase and cytochrome oxidase, the activity of only the latter was markedly reduced by a chronic sympathetic denervation. From the results obtained it is concluded that neonatal treatment with 6-hydroxy-dopamine causes a permanent and almost complete sympathectomy of the submaxillary gland of the rat."} {"id": "PMID:169486", "title": "The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle.", "content": "In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP.", "contents": "The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle. In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP."} {"id": "PMID:169487", "title": "On the role of alpha-methyldopamine in the antihypertensive effect of alpha-methyldopa.", "content": "In renal hypertensive rats the cerebral concentration of alpha-methyldopa, alpha-methyldopamine, alpha-methylnoradrenaline, dopamine and noradrenaline as well as the blood-pressure were determined simultaneously. The antihypertensive effect followed a time course identical to that of the increase in the cerebral concentration of alpha-methyldopamine and of the decrease in the concentration of dopamine, whereas lowering of blood pressure on the one hand, and changes in the levels of alpha-methylnoradrenaline and noradrenaline, on the other, were not related to each other. Dose-response relationships showed the same correlations and lack of correlations, respectively. These results suggest that non-betat-hydroxylated catecholamines play a major role in mediating the antihypertensive effect of alpha-methyldopa or, alternatively, that only the newly biosynthesized alpha-methyl-noradrenaline is effective in lowering blood pressure.", "contents": "On the role of alpha-methyldopamine in the antihypertensive effect of alpha-methyldopa. In renal hypertensive rats the cerebral concentration of alpha-methyldopa, alpha-methyldopamine, alpha-methylnoradrenaline, dopamine and noradrenaline as well as the blood-pressure were determined simultaneously. The antihypertensive effect followed a time course identical to that of the increase in the cerebral concentration of alpha-methyldopamine and of the decrease in the concentration of dopamine, whereas lowering of blood pressure on the one hand, and changes in the levels of alpha-methylnoradrenaline and noradrenaline, on the other, were not related to each other. Dose-response relationships showed the same correlations and lack of correlations, respectively. These results suggest that non-betat-hydroxylated catecholamines play a major role in mediating the antihypertensive effect of alpha-methyldopa or, alternatively, that only the newly biosynthesized alpha-methyl-noradrenaline is effective in lowering blood pressure."} {"id": "PMID:169489", "title": "Polypeptides isolated from ribosome-like structures occluded in avian myeloblastosis virus (AMV).", "content": "The protein composititon of ribosome-like particles isolated from AMV was determined by acrylamide gel electrophoresis and by immunological methods. It was established that the protein spectrum of ribosome-like particles differed significantly form the total protein spectrum of AMV. The most characteristic protein components of ribosome-like particles had a molecular weight in the range of 70 000--110 000. Apart from these proteins, the viral ribosomal particles contained a small amount of proteins with a molecular weight of 14 000--35 000 that could not be removed even by extensive purification. Immunological studies of the proteins of ribosome-like particles revealed the presence of antigenic determinants of ribosomal proteins. Furthermore, throughout the purification procedure the material contained components that reacted with antibodies against gs antigens.", "contents": "Polypeptides isolated from ribosome-like structures occluded in avian myeloblastosis virus (AMV). The protein composititon of ribosome-like particles isolated from AMV was determined by acrylamide gel electrophoresis and by immunological methods. It was established that the protein spectrum of ribosome-like particles differed significantly form the total protein spectrum of AMV. The most characteristic protein components of ribosome-like particles had a molecular weight in the range of 70 000--110 000. Apart from these proteins, the viral ribosomal particles contained a small amount of proteins with a molecular weight of 14 000--35 000 that could not be removed even by extensive purification. Immunological studies of the proteins of ribosome-like particles revealed the presence of antigenic determinants of ribosomal proteins. Furthermore, throughout the purification procedure the material contained components that reacted with antibodies against gs antigens."} {"id": "PMID:169490", "title": "Mammalian tropism of B77(RBI) virus. Expression of virus genome in the hamster sarcoma cell clones.", "content": "In contrast to the B77 virus, its B77(RBI) rat variant continuously produced by the rat RBI sarcoma cells in vivo and in vitro, efficiently induced progressively growing tumors in hamsters and transformed hamster embryo cells in vitro. Both, induced tumors and transformed cell cultures showed production of infectious virus and presence of the avian gs-antigen. Clonal analysis of the established hamster sarcoma cell line RBHtc brought evidence that despite the quantitative differences in the virus production and gs-antigen content among various clonal populations, full expression of the B77(RBI) virus genome does occur in each cell of the virus-induced hamster sarcoma. The permissive relationship of the B77(RBI) virus with rat and hamster cells as well as changed antigenic composititon implies that a genetic change of the virus occured, which is reflected in its increased mammalian tropism and its genetically stable firus-productive interaction with mammalian cells. The possible explanations of these phenomena are discussed.", "contents": "Mammalian tropism of B77(RBI) virus. Expression of virus genome in the hamster sarcoma cell clones. In contrast to the B77 virus, its B77(RBI) rat variant continuously produced by the rat RBI sarcoma cells in vivo and in vitro, efficiently induced progressively growing tumors in hamsters and transformed hamster embryo cells in vitro. Both, induced tumors and transformed cell cultures showed production of infectious virus and presence of the avian gs-antigen. Clonal analysis of the established hamster sarcoma cell line RBHtc brought evidence that despite the quantitative differences in the virus production and gs-antigen content among various clonal populations, full expression of the B77(RBI) virus genome does occur in each cell of the virus-induced hamster sarcoma. The permissive relationship of the B77(RBI) virus with rat and hamster cells as well as changed antigenic composititon implies that a genetic change of the virus occured, which is reflected in its increased mammalian tropism and its genetically stable firus-productive interaction with mammalian cells. The possible explanations of these phenomena are discussed."} {"id": "PMID:169491", "title": "The experience with clinical application of hydron pouches in tumor chemotherapy.", "content": "Hydron pouches were applied in three cases of embryonal hepatomas in infants. Cyclophosphamide (one case) and methotrexate (two cases) were used for filling of pouches in order to accomplish local chemotherapeutical effect directly on the tumor. Histopathological examination showed good compatibility of pouches to the liver tissue. No therapeutical effect was observed in a set of experiments due to a small size of pouches as compared to big masses of tumor. Some suggestions for further development of this method are presented.", "contents": "The experience with clinical application of hydron pouches in tumor chemotherapy. Hydron pouches were applied in three cases of embryonal hepatomas in infants. Cyclophosphamide (one case) and methotrexate (two cases) were used for filling of pouches in order to accomplish local chemotherapeutical effect directly on the tumor. Histopathological examination showed good compatibility of pouches to the liver tissue. No therapeutical effect was observed in a set of experiments due to a small size of pouches as compared to big masses of tumor. Some suggestions for further development of this method are presented."} {"id": "PMID:169493", "title": "In vitro cellular responsiveness in multiple sclerosis patients to a viral isolate from multiple sclerosis brain tissue and to other antigens.", "content": "The Clausen modification of the leukocyte migration test was used to test patients with multiple sclerosis, normal subjects, and patients with other neurologic diseases for cell-mediated immunity to 6/94 virus (a parainfluenza virus previously isolated from the brain tissue of a multiple sclerosis patient), c-RNA virus isolated from a tumor, and the nonviral antigens Candida and purified protein derivative. Leukocytes of multiple sclerosis patient showed significantly less mean inhibition of migration by the 6/94 virus (but not by the c-RNA virus, purified protein derivative, and Candida) than did the cells of normal controls and patients with other neurologic diseases. The relationship of these findings to previous observations in this area and to the pathogenesis of multiple sclerosis is discussed.", "contents": "In vitro cellular responsiveness in multiple sclerosis patients to a viral isolate from multiple sclerosis brain tissue and to other antigens. The Clausen modification of the leukocyte migration test was used to test patients with multiple sclerosis, normal subjects, and patients with other neurologic diseases for cell-mediated immunity to 6/94 virus (a parainfluenza virus previously isolated from the brain tissue of a multiple sclerosis patient), c-RNA virus isolated from a tumor, and the nonviral antigens Candida and purified protein derivative. Leukocytes of multiple sclerosis patient showed significantly less mean inhibition of migration by the 6/94 virus (but not by the c-RNA virus, purified protein derivative, and Candida) than did the cells of normal controls and patients with other neurologic diseases. The relationship of these findings to previous observations in this area and to the pathogenesis of multiple sclerosis is discussed."} {"id": "PMID:169494", "title": "Mononeuropathy due to vincristine toxicity.", "content": "Vincristine sulfate is a known neurotoxin. Peripheral neuropathy is the most common toxic manifestation and is usually of the symmetrical, mixed, sensory-motor type. With this report we alert other physicians to another feature of vincristine neurotoxicity, namely, mononeuropathy.", "contents": "Mononeuropathy due to vincristine toxicity. Vincristine sulfate is a known neurotoxin. Peripheral neuropathy is the most common toxic manifestation and is usually of the symmetrical, mixed, sensory-motor type. With this report we alert other physicians to another feature of vincristine neurotoxicity, namely, mononeuropathy."} {"id": "PMID:169495", "title": "Some perspectives on the role of biostatistics and epidemiology in the prevention and control of mental disorders.", "content": "The paper reviews progress made in the past 30 years in the development of statistical and epidemiological methods in the mental health field. Applications have included determinations of need for psychiatric care and supporting personnel; interpretation of morbidity indices, and cross-national comparisons of diagnoses of mental disorders. Much remains to be done. Progress would include better measurement of incidence, duration, and prevalence of mental disorders; more precise estimates of service needs; more effective programs to prevent or reduce disability. Particularly needed are field-research units under long-term funding with the task of assessing effectiveness of mental health programs at the catchment-area level.", "contents": "Some perspectives on the role of biostatistics and epidemiology in the prevention and control of mental disorders. The paper reviews progress made in the past 30 years in the development of statistical and epidemiological methods in the mental health field. Applications have included determinations of need for psychiatric care and supporting personnel; interpretation of morbidity indices, and cross-national comparisons of diagnoses of mental disorders. Much remains to be done. Progress would include better measurement of incidence, duration, and prevalence of mental disorders; more precise estimates of service needs; more effective programs to prevent or reduce disability. Particularly needed are field-research units under long-term funding with the task of assessing effectiveness of mental health programs at the catchment-area level."} {"id": "PMID:169499", "title": "Neurological complications of haemophilia.", "content": "Peripheral nerve lesions are well recognised complications of the haemophilias but impairment of autonomic function has not previously been reported. Two patients of the severe older haemophiliac population in the area were found to have impotence in association with signs of peripheral nerve damage. The basis proposed for this is autonomic nerve injury associated with intramuscular haemorrhage.", "contents": "Neurological complications of haemophilia. Peripheral nerve lesions are well recognised complications of the haemophilias but impairment of autonomic function has not previously been reported. Two patients of the severe older haemophiliac population in the area were found to have impotence in association with signs of peripheral nerve damage. The basis proposed for this is autonomic nerve injury associated with intramuscular haemorrhage."} {"id": "PMID:169500", "title": "Response of pituitary-adrenal axis on partal stress.", "content": "The circulating level of ACTH (by radioimmunoassay) and cortisol (by competitive protein binding) were determined at 1- to 2-hour intervals during spontaneous labor (N=8) and induced labor (N=28) and after delivery. There were no differences in ACTH levels between primiparous and multiparous women. The primiparous women displayed a higher level of cortisol throughout labor than the multiparous women, but not after delivery. After spontaneous onset of labor, ACTH levels were always lower than after elective induction of labor, while there were no differences in the levels of cortisol. The hypertensive complications of pregnancy did not affect the secretion of ACTH. In normal pregnancy the rise of cortisol during labor and after delivery was significant, but it was not significant in the group of patients with hypertensive complications.", "contents": "Response of pituitary-adrenal axis on partal stress. The circulating level of ACTH (by radioimmunoassay) and cortisol (by competitive protein binding) were determined at 1- to 2-hour intervals during spontaneous labor (N=8) and induced labor (N=28) and after delivery. There were no differences in ACTH levels between primiparous and multiparous women. The primiparous women displayed a higher level of cortisol throughout labor than the multiparous women, but not after delivery. After spontaneous onset of labor, ACTH levels were always lower than after elective induction of labor, while there were no differences in the levels of cortisol. The hypertensive complications of pregnancy did not affect the secretion of ACTH. In normal pregnancy the rise of cortisol during labor and after delivery was significant, but it was not significant in the group of patients with hypertensive complications."} {"id": "PMID:169501", "title": "Invasive vulvar Paget's disease.", "content": "Seven cases of invasive vulvar Paget's disease are presented. These are compared with 10 cases of intraepithelial vulvar Paget's disease. On the basis of both clinical and histopathologic observations, the concept of intraepithelial vulvar Paget's disease is supported, and this entity is distinguished from the invasive form. Therapy for the latter is discussed.", "contents": "Invasive vulvar Paget's disease. Seven cases of invasive vulvar Paget's disease are presented. These are compared with 10 cases of intraepithelial vulvar Paget's disease. On the basis of both clinical and histopathologic observations, the concept of intraepithelial vulvar Paget's disease is supported, and this entity is distinguished from the invasive form. Therapy for the latter is discussed."} {"id": "PMID:169502", "title": "Dermatitis from neutral red therapy of herpes genitalis.", "content": "A case of contact dermatitis from neutral red dye applied for treatment of herpes genitalis is presented. A review of the literature revealed 5 other patients with a similar reaction. We suggest that neutral red dye treatment for herpes should be used with caution in patients with an allergic history.", "contents": "Dermatitis from neutral red therapy of herpes genitalis. A case of contact dermatitis from neutral red dye applied for treatment of herpes genitalis is presented. A review of the literature revealed 5 other patients with a similar reaction. We suggest that neutral red dye treatment for herpes should be used with caution in patients with an allergic history."} {"id": "PMID:169506", "title": "Growth and skeletal maturation in asthmatic children: effect of corticosteroid treatment.", "content": "The effects of corticosteroid treatment on growth and skeletal maturation were evaluated in 189 children with severe asthma who were referred for care at a residential treatment center. Height age on admission was significantly retarded in 8-10% of patients who had received little corticosteroid treatment previously and in 35% of patients who had taken steroids daily for more than 2 years. Children who had been treated with steroids intermittently or on alternate days were comparable to those who had taken steroids rarely. During an average residential period of 17 months, patients whose daily steroid treatment was discontinued had a relative gain in height age of 5 months; children who were started on daily steroids had a 5-month delay in growth. Evaluation of skeletal maturation at the time of admission revealed that skeletal age was more retarded than height age in the boys and less retarded than the height age in the girls. During the period of residence, the changes in bone age paralleled the changes in height age.", "contents": "Growth and skeletal maturation in asthmatic children: effect of corticosteroid treatment. The effects of corticosteroid treatment on growth and skeletal maturation were evaluated in 189 children with severe asthma who were referred for care at a residential treatment center. Height age on admission was significantly retarded in 8-10% of patients who had received little corticosteroid treatment previously and in 35% of patients who had taken steroids daily for more than 2 years. Children who had been treated with steroids intermittently or on alternate days were comparable to those who had taken steroids rarely. During an average residential period of 17 months, patients whose daily steroid treatment was discontinued had a relative gain in height age of 5 months; children who were started on daily steroids had a 5-month delay in growth. Evaluation of skeletal maturation at the time of admission revealed that skeletal age was more retarded than height age in the boys and less retarded than the height age in the girls. During the period of residence, the changes in bone age paralleled the changes in height age."} {"id": "PMID:169507", "title": "1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance.", "content": "This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, \"pseudodeficiency\" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.", "contents": "1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance. This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, \"pseudodeficiency\" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder."} {"id": "PMID:169508", "title": "Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents.", "content": "Levodopa, 0.5 gm/1.73 sq m, and propranolol, 0.75 mg/kg, were administered orally to 23 children with short stature and 10 children suffering from various disorders. Glucose and insulin tolerance tests and arginine infusions were also utilized in some of these subjects to determine growth hormone (GH) response. Seventeen subjects with short stature had a GH peak greater than 5 ng/ml to the combined levodopa-propranolol provocative test (DPPT). The mean GH peak concentration obtained in this group was 19.6 +/- 1.8 (SEM) ng/ml, and in 94.1% of these children the peak was obtained at either 30, 60, or 90 minutes following the administration of the two drugs. Six subjects with short stature who failed to respond to the DPPT had abnormal responses to at least two other stimulatory tests and were classified as GH-deficient. Two subjects among the ten suffering from various disorders failed to respond to the DPPT. The first was a case of chromophobe adenoma of the pituitary gland with primary amenorrhea and luteinizing hormone deficiency, and the second a case of Hand-Sch\u00fcller-Christian disease. The DPPT appears to be a reliable, safe, and easy-to-perform test to determine GH reserve.", "contents": "Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents. Levodopa, 0.5 gm/1.73 sq m, and propranolol, 0.75 mg/kg, were administered orally to 23 children with short stature and 10 children suffering from various disorders. Glucose and insulin tolerance tests and arginine infusions were also utilized in some of these subjects to determine growth hormone (GH) response. Seventeen subjects with short stature had a GH peak greater than 5 ng/ml to the combined levodopa-propranolol provocative test (DPPT). The mean GH peak concentration obtained in this group was 19.6 +/- 1.8 (SEM) ng/ml, and in 94.1% of these children the peak was obtained at either 30, 60, or 90 minutes following the administration of the two drugs. Six subjects with short stature who failed to respond to the DPPT had abnormal responses to at least two other stimulatory tests and were classified as GH-deficient. Two subjects among the ten suffering from various disorders failed to respond to the DPPT. The first was a case of chromophobe adenoma of the pituitary gland with primary amenorrhea and luteinizing hormone deficiency, and the second a case of Hand-Sch\u00fcller-Christian disease. The DPPT appears to be a reliable, safe, and easy-to-perform test to determine GH reserve."} {"id": "PMID:169521", "title": "Reduction of Clostridium perfringens by feed additive antibiotics in the ceca of chickens infected with Eimeria tenella.", "content": "Two experiments were performed ot investigate the effect of feed additive antibiotics on Clostridium perfringens and Enterobacteriaceae in the ceca of chickens infected with Eimeria tenella. In the first experiment, chickens were continuously fed rations containing thiopeptin, 2 mg./kg.; bacitracin, 20 mg./kg.; penicillin, 12 mg./kg.; or chlortetracycline, 22 mg./kg. One day after antibiotic feed was given, each bird received an oral inoculation of 30,000 E. tenella oocysts. The growth of C. perfringens was stimulated by the infection in unmedicated chickens. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline suppressed the number of C. perfringens recovered 5 and 7 days after infection. Enterobacteriaceae were increased by the infection, but dietary antibiotics did not reduce the increase. In the second experiment, chickens were given feed containing amprolium plus ethopabate, 125 plus 8 mg./kg., and a combination of the coccidiostat and one of 4 antibiotics: thiopeptin, bacitracin, penicillin, or chlortetracycline. Birds were each given an oral inoculation of 30,000 coccidiostat-resistant E. tenella oocysts. Infection resulted in an increase of C. perfringens in the unmedicated control and the coccidiostat-treated groups. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline reduced the number of C. perfringens found 5 and 7 days after infection. Counts of Enterobacteriaceae were increased by the infection, but dietary antibiotics did not suppress the increased counts. In both experiments, dietary administration of antibiotics did not reduce gross cecal lesions.", "contents": "Reduction of Clostridium perfringens by feed additive antibiotics in the ceca of chickens infected with Eimeria tenella. Two experiments were performed ot investigate the effect of feed additive antibiotics on Clostridium perfringens and Enterobacteriaceae in the ceca of chickens infected with Eimeria tenella. In the first experiment, chickens were continuously fed rations containing thiopeptin, 2 mg./kg.; bacitracin, 20 mg./kg.; penicillin, 12 mg./kg.; or chlortetracycline, 22 mg./kg. One day after antibiotic feed was given, each bird received an oral inoculation of 30,000 E. tenella oocysts. The growth of C. perfringens was stimulated by the infection in unmedicated chickens. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline suppressed the number of C. perfringens recovered 5 and 7 days after infection. Enterobacteriaceae were increased by the infection, but dietary antibiotics did not reduce the increase. In the second experiment, chickens were given feed containing amprolium plus ethopabate, 125 plus 8 mg./kg., and a combination of the coccidiostat and one of 4 antibiotics: thiopeptin, bacitracin, penicillin, or chlortetracycline. Birds were each given an oral inoculation of 30,000 coccidiostat-resistant E. tenella oocysts. Infection resulted in an increase of C. perfringens in the unmedicated control and the coccidiostat-treated groups. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline reduced the number of C. perfringens found 5 and 7 days after infection. Counts of Enterobacteriaceae were increased by the infection, but dietary antibiotics did not suppress the increased counts. In both experiments, dietary administration of antibiotics did not reduce gross cecal lesions."} {"id": "PMID:169524", "title": "Assignment of gene(s) for cell transformation to human chromosome 7 carrying the simian virus 40 genome.", "content": "Somatic cell hybrid clones between either C57BL/6 or Balb/c mouse peritoneal macrophages and two different simian virus 40 (SV40)-transformed human cell lines deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase) were obtained in hypoxanthine-aminopterin-thymidine selective medium. All the hybrid cell clones contained the human chromosome 7, which carries the SV40 genome, and were SV40 tumor (T)-antigen positive. No hybrid cell clones studied displayed the density-dependent inhibition of cell growth characteristic of normal cells; all clones had a high saturation density and gave origin to cell colonies when plated in soft agar. Since the expression of the transformed phenotype was always associated with the presence of the human chromosome 7, which carries the SV40 genome, it is concluded that this chromosome contains gene(s) [Tr gene(s)] coding for \"transforming factor(s).\"", "contents": "Assignment of gene(s) for cell transformation to human chromosome 7 carrying the simian virus 40 genome. Somatic cell hybrid clones between either C57BL/6 or Balb/c mouse peritoneal macrophages and two different simian virus 40 (SV40)-transformed human cell lines deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase) were obtained in hypoxanthine-aminopterin-thymidine selective medium. All the hybrid cell clones contained the human chromosome 7, which carries the SV40 genome, and were SV40 tumor (T)-antigen positive. No hybrid cell clones studied displayed the density-dependent inhibition of cell growth characteristic of normal cells; all clones had a high saturation density and gave origin to cell colonies when plated in soft agar. Since the expression of the transformed phenotype was always associated with the presence of the human chromosome 7, which carries the SV40 genome, it is concluded that this chromosome contains gene(s) [Tr gene(s)] coding for \"transforming factor(s).\""} {"id": "PMID:169525", "title": "Augmentation of lymphocyte cytotoxicity by antibody to herpesvirus saimiri associated antigens.", "content": "Sera from owl monkeys infected with Herpesvirus saimiri (HVS) mediated antibody-dependent lymphocyte cytotoxicity (ADLC) against virus-infected owl monkey kidney cells. Peripheral blood lymphocytes from rhesus monkeys served as effector cells in this cytotoxic assay. ADLC titers increased along with membrane immunofluorescence (MF) titers but among some sera, the ADLC titers were much higher than expected from the MF titers, suggesting that multiple serum factors were involved in mediating ADLC in this system. Absorption of both low and high titered sera with HVS-infected owl monkey kidney cells removed all ADLC activity. Preliminary results from serial serum samples from two infected monkeys that developed leukemia and/or lymphoma demonstrated that ADLC but not MF titers increased to high titers with progression of disease and followed essentially a different kinetic pattern than that noted by MF. The possible significance of these findings in relation to malignant disease induced by this virus is discussed.", "contents": "Augmentation of lymphocyte cytotoxicity by antibody to herpesvirus saimiri associated antigens. Sera from owl monkeys infected with Herpesvirus saimiri (HVS) mediated antibody-dependent lymphocyte cytotoxicity (ADLC) against virus-infected owl monkey kidney cells. Peripheral blood lymphocytes from rhesus monkeys served as effector cells in this cytotoxic assay. ADLC titers increased along with membrane immunofluorescence (MF) titers but among some sera, the ADLC titers were much higher than expected from the MF titers, suggesting that multiple serum factors were involved in mediating ADLC in this system. Absorption of both low and high titered sera with HVS-infected owl monkey kidney cells removed all ADLC activity. Preliminary results from serial serum samples from two infected monkeys that developed leukemia and/or lymphoma demonstrated that ADLC but not MF titers increased to high titers with progression of disease and followed essentially a different kinetic pattern than that noted by MF. The possible significance of these findings in relation to malignant disease induced by this virus is discussed."} {"id": "PMID:169526", "title": "A structural change of the plasma membrane induced by oncogenic viruses: quantitative studies with the freeze-fracture technique.", "content": "In BHK21 hamster cells a significant increase in density of intramembranous particles occurs in freeze-fractured plasma membranes after transformation by hamster sarcoma and polyoma viruses. A similar change has been observed in chick embryo cells infected and transformed by a mutant of Rous sarcoma virus thermosensitive for transformation, at both permissive and nonpermissive temperatures. There is also an increase in particle density in chick cells infected with the Rous-associated avian leukosis virus type 1. The newly appeared particles may represent the insertion of new proteins in hydrophobic regions of plasma membrane, in response to the action of oncogenic viruses.", "contents": "A structural change of the plasma membrane induced by oncogenic viruses: quantitative studies with the freeze-fracture technique. In BHK21 hamster cells a significant increase in density of intramembranous particles occurs in freeze-fractured plasma membranes after transformation by hamster sarcoma and polyoma viruses. A similar change has been observed in chick embryo cells infected and transformed by a mutant of Rous sarcoma virus thermosensitive for transformation, at both permissive and nonpermissive temperatures. There is also an increase in particle density in chick cells infected with the Rous-associated avian leukosis virus type 1. The newly appeared particles may represent the insertion of new proteins in hydrophobic regions of plasma membrane, in response to the action of oncogenic viruses."} {"id": "PMID:169527", "title": "Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 5: Effects of lubricants and flow conditions.", "content": "The effect of talc, magnesium stearate, stearic acid, and Acrawax C, which are commonly used as lubricants, on the dry-binding efficiency of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone, and mannitol were investigated. The effect of Aerosil which is sometimes utilized as a flow conditioner for directly compressible powder blends was also studied. The type and concentration of lubricant or flow conditioner appeared to influence the binding efficiency of the binders investigated to various degrees. The results showed that the bonding characteristics of all the binders tested except mannitol were reduced by the addition of the lubricants and the flow conditioner.", "contents": "Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 5: Effects of lubricants and flow conditions. The effect of talc, magnesium stearate, stearic acid, and Acrawax C, which are commonly used as lubricants, on the dry-binding efficiency of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone, and mannitol were investigated. The effect of Aerosil which is sometimes utilized as a flow conditioner for directly compressible powder blends was also studied. The type and concentration of lubricant or flow conditioner appeared to influence the binding efficiency of the binders investigated to various degrees. The results showed that the bonding characteristics of all the binders tested except mannitol were reduced by the addition of the lubricants and the flow conditioner."} {"id": "PMID:169529", "title": "The development of mitochondrial oxidative enzymes in rat heart muscle.", "content": "Three different developmental patterns have been found in the heart muscle mitochondria: (a) Activity of inner membrane enzymes, succinate-cytochrome c reductase and rotenone-sensitive NADH-cytochrome c reductase, was found to increase rapidly after birth till the 25th day; no further increase was found till the 60th day. Both brances of the respiratory chain, i.e. NADH-dependent and flavoprotein-linked were found to develop in parallel. (b) Activity of retoenone insensitive-NADH cytochrome c reductase, an outer membrane enzyme, did not show any change during developement. (c) Activity of monoamine oxidase, another outer membrane enzyme, was found to increase after the 10th day of postnatal life and the increase in activity continued till the 60th day.", "contents": "The development of mitochondrial oxidative enzymes in rat heart muscle. Three different developmental patterns have been found in the heart muscle mitochondria: (a) Activity of inner membrane enzymes, succinate-cytochrome c reductase and rotenone-sensitive NADH-cytochrome c reductase, was found to increase rapidly after birth till the 25th day; no further increase was found till the 60th day. Both brances of the respiratory chain, i.e. NADH-dependent and flavoprotein-linked were found to develop in parallel. (b) Activity of retoenone insensitive-NADH cytochrome c reductase, an outer membrane enzyme, did not show any change during developement. (c) Activity of monoamine oxidase, another outer membrane enzyme, was found to increase after the 10th day of postnatal life and the increase in activity continued till the 60th day."} {"id": "PMID:169530", "title": "Activity of the inner and outer membrane oxidative enzymes in brown adipose tissue mitochondria.", "content": "1. The specific activity of cytochrome-oxidase, succinate-cytochrome c reductase and su-cinate-oxidase of brown adipose tissue mitochondria of 17-day-old rats was found to be twice as high in brwon adipose tissue mitochondria as in the liver. The specific activity of rotenone-sensitive NADH-cytochrome c reductase and NADH-oxidase was found to be six times higher in brown adipose tissue mitochondria than in the liver. 2. Brown adipose tissue mitochondria have extremely low activity of outer membrane enzymes. When compared with liver the specific activity of rotenone-insensitive NADH-cytochrome c reductase was found to be seven times lower, the specific activity of monoamineoxidase up to 30 times lower according to the substrate used. 3. The optimum conditions for the determination of both NADH-cytochrome c reductases in brown adipose tissue mitochondria were more specified on the base of the following findings: (a) the outer membrane rotenone-insensitive NADH-cytochrome c reductase is strongly inactivated by freezing-thawing, (b) freezing-thawing, alone is insufficient to release completely maximal activity of rotenone-sensitive NADH-cytochrone c reductase, freezing-thawing activite can be further potentiated by e.g. trypsin treatment. 4. The activities of the outer membranes of brown-adipose tissue mitochondria are discussed with regards to the structural integrity of the outer membrane, the activities of the inner membrane enzymes are discussed with regards to the functional specifity of the tissue.", "contents": "Activity of the inner and outer membrane oxidative enzymes in brown adipose tissue mitochondria. 1. The specific activity of cytochrome-oxidase, succinate-cytochrome c reductase and su-cinate-oxidase of brown adipose tissue mitochondria of 17-day-old rats was found to be twice as high in brwon adipose tissue mitochondria as in the liver. The specific activity of rotenone-sensitive NADH-cytochrome c reductase and NADH-oxidase was found to be six times higher in brown adipose tissue mitochondria than in the liver. 2. Brown adipose tissue mitochondria have extremely low activity of outer membrane enzymes. When compared with liver the specific activity of rotenone-insensitive NADH-cytochrome c reductase was found to be seven times lower, the specific activity of monoamineoxidase up to 30 times lower according to the substrate used. 3. The optimum conditions for the determination of both NADH-cytochrome c reductases in brown adipose tissue mitochondria were more specified on the base of the following findings: (a) the outer membrane rotenone-insensitive NADH-cytochrome c reductase is strongly inactivated by freezing-thawing, (b) freezing-thawing, alone is insufficient to release completely maximal activity of rotenone-sensitive NADH-cytochrone c reductase, freezing-thawing activite can be further potentiated by e.g. trypsin treatment. 4. The activities of the outer membranes of brown-adipose tissue mitochondria are discussed with regards to the structural integrity of the outer membrane, the activities of the inner membrane enzymes are discussed with regards to the functional specifity of the tissue."} {"id": "PMID:169532", "title": "REM sleep and the analytic process: a psychophysiologic bridge.", "content": "Recent research on the physiology of REM sleep has supported the hypothesis that it serves processes of psychologic adaptation. This study examines the relationship between physiologic parameters of REM sleep and evidence in analytic material of the need for adaptation. Significant correlations were found between defensive strain before sleep and REM latency, and between change in defensive strain from evening to morning and total REM time.", "contents": "REM sleep and the analytic process: a psychophysiologic bridge. Recent research on the physiology of REM sleep has supported the hypothesis that it serves processes of psychologic adaptation. This study examines the relationship between physiologic parameters of REM sleep and evidence in analytic material of the need for adaptation. Significant correlations were found between defensive strain before sleep and REM latency, and between change in defensive strain from evening to morning and total REM time."} {"id": "PMID:169533", "title": "Clinical measurement in psychoanalysis: an approach.", "content": "Measurement of the complex phenomena in psychoanalysis is approached by defining interrelated elements in the analytic situation and specifying the range of their variation in scales which can be both generalized and made specific for an individual patient. Using this approach in transcripts of psychoanalytic sessions, we rate painful emotion, impairment of defensive maneuvers, and activation of threatening conflictual fantasies. This preliminary study involved rating of tape-recorded sessions by psychoanalytically oriented judges. Quantitative estimates appeared to relate in many ways to qualitative fluctuations in the patient's state. Such an approach may be helpful in developing more effective clinical theory about emotions, defensive processes, and transference fantasies.", "contents": "Clinical measurement in psychoanalysis: an approach. Measurement of the complex phenomena in psychoanalysis is approached by defining interrelated elements in the analytic situation and specifying the range of their variation in scales which can be both generalized and made specific for an individual patient. Using this approach in transcripts of psychoanalytic sessions, we rate painful emotion, impairment of defensive maneuvers, and activation of threatening conflictual fantasies. This preliminary study involved rating of tape-recorded sessions by psychoanalytically oriented judges. Quantitative estimates appeared to relate in many ways to qualitative fluctuations in the patient's state. Such an approach may be helpful in developing more effective clinical theory about emotions, defensive processes, and transference fantasies."} {"id": "PMID:169536", "title": "Some effects of ACTH 4-10 on performance during a serial reaction task.", "content": "Eighteen subjects worked continuously for half an hour in a self-paced reaction task. Half of the subjects were injected with ACTH 4-10 (30 mg/s.c.) and the other half with a placebo. The subjects injected with ACTH 4-10 showed a larger improvement in reaction time during the experimental session than the placebo group. However, this effect disappeared in a short retest, which was given half an hour after the experimental session. These results suggest that ACTH 4-10 has no effect on skill acquisition, but counteracts the build-up of reactive inhibition during the experimental session; that is, the peptide suppresses the decrease in motivation, which usually occurs during continuous performance tasks. This notion is confirmed by an analysis of the frequency distributions of the reaction times. Treatment effects were only found for the long reaction times. Long reaction times tend to occur with increasing frequency as a function of time-on-task and are an indication for the level of motivation of the subject. It was concluded that ACTH 4-10 counteracts the usual decay in performance as a function of time-on-task due to increasing boredom and mental fatigue.", "contents": "Some effects of ACTH 4-10 on performance during a serial reaction task. Eighteen subjects worked continuously for half an hour in a self-paced reaction task. Half of the subjects were injected with ACTH 4-10 (30 mg/s.c.) and the other half with a placebo. The subjects injected with ACTH 4-10 showed a larger improvement in reaction time during the experimental session than the placebo group. However, this effect disappeared in a short retest, which was given half an hour after the experimental session. These results suggest that ACTH 4-10 has no effect on skill acquisition, but counteracts the build-up of reactive inhibition during the experimental session; that is, the peptide suppresses the decrease in motivation, which usually occurs during continuous performance tasks. This notion is confirmed by an analysis of the frequency distributions of the reaction times. Treatment effects were only found for the long reaction times. Long reaction times tend to occur with increasing frequency as a function of time-on-task and are an indication for the level of motivation of the subject. It was concluded that ACTH 4-10 counteracts the usual decay in performance as a function of time-on-task due to increasing boredom and mental fatigue."} {"id": "PMID:169537", "title": "[Effects of alpha-methyl-dopa on new born kitten sleep. Behavioral evolution during the first month post-birth (author's transl)].", "content": "The paradoxical sleep (PS)-suppressing effect of alpha-methyl-Dopa was studied in kittens at birth. The new burn animal received daily injections of alpha-methyl-Dopa during the 2 first weeks of life. States of sleep were studied during the treatment (days 1 to 14) and after administration of the drug way halted (days 15 and 16). Daily injections of alpha-methyl-Dopa induce an average PS-deprivation of 72%. This deprievation is compensated for by a significant increase in quiet sleep (QS)-rate which is found to be up to 3.5 times that of kittens not receiving alpha-methyl-Dopa. A progressive return of PS-ratio to normal, without PS rebound, is observed after drug administration ceases. Alpha-methyl-Dopa produces a sedative effect on the kitten which remains relatively hypotonic during the treatment. Behavioural studies carried out over the first month after birth show no significant delay in the ponderal growth nor in the acquisition of stereotyped behaviour patterns. However motor coordination is delayed 2 weeks in these kittens.", "contents": "[Effects of alpha-methyl-dopa on new born kitten sleep. Behavioral evolution during the first month post-birth (author's transl)]. The paradoxical sleep (PS)-suppressing effect of alpha-methyl-Dopa was studied in kittens at birth. The new burn animal received daily injections of alpha-methyl-Dopa during the 2 first weeks of life. States of sleep were studied during the treatment (days 1 to 14) and after administration of the drug way halted (days 15 and 16). Daily injections of alpha-methyl-Dopa induce an average PS-deprivation of 72%. This deprievation is compensated for by a significant increase in quiet sleep (QS)-rate which is found to be up to 3.5 times that of kittens not receiving alpha-methyl-Dopa. A progressive return of PS-ratio to normal, without PS rebound, is observed after drug administration ceases. Alpha-methyl-Dopa produces a sedative effect on the kitten which remains relatively hypotonic during the treatment. Behavioural studies carried out over the first month after birth show no significant delay in the ponderal growth nor in the acquisition of stereotyped behaviour patterns. However motor coordination is delayed 2 weeks in these kittens."} {"id": "PMID:169538", "title": "Effects of a new butyrophenone derivate (Buronil) on nocturnal sleep in normal man.", "content": "Nocturnal sleep was studied in eight young normal volunteers (3 female and 5 male students) with polygraphic technique during 2 periods of 10 night each. After 2 adaptation and 2 baseline nights with placebo, they were given methylperone (Buronil) 10 or 50 mg per night during three nights and then again placebo for three withdrawal nights. The study was made double blind. The scoring of the records was done according to the manual by Rechtschaffen and Kales (1968). No changes of sleep stages were seen during the drug periods. The lower dose gave an increase of sleep latency but a decrease of number of awakenings during the night. An increase of REM-periods was shown after 50 mg and also a decrease of REM-latency and REM-density. The only significant change during withdrawal periods was a decrease of REM-sleep after methylperone 50 mg, so there was no \"barbiturate type\" of withdrawal. The change was also different from that of chloropromazine, which has no clear rebound effect.", "contents": "Effects of a new butyrophenone derivate (Buronil) on nocturnal sleep in normal man. Nocturnal sleep was studied in eight young normal volunteers (3 female and 5 male students) with polygraphic technique during 2 periods of 10 night each. After 2 adaptation and 2 baseline nights with placebo, they were given methylperone (Buronil) 10 or 50 mg per night during three nights and then again placebo for three withdrawal nights. The study was made double blind. The scoring of the records was done according to the manual by Rechtschaffen and Kales (1968). No changes of sleep stages were seen during the drug periods. The lower dose gave an increase of sleep latency but a decrease of number of awakenings during the night. An increase of REM-periods was shown after 50 mg and also a decrease of REM-latency and REM-density. The only significant change during withdrawal periods was a decrease of REM-sleep after methylperone 50 mg, so there was no \"barbiturate type\" of withdrawal. The change was also different from that of chloropromazine, which has no clear rebound effect."} {"id": "PMID:169543", "title": "Ultrastructural changes in the placenta of the ewe following foetal infusion of cortisol.", "content": "The placental changes which followed continuous infusion of cortisol into the sheep foetus in the later stages of gestation were, like the hormonal changes, broadly similar to those of spontaneous parturition. There was, however, a premature separation of foetal and maternal tissues in certain areas of the placental cotyledons, and this separation appeared to protect the foetal epithelium from the degenerative changes which normally take place in the short space of time between the birth of the lamb and the delivery of the foetal membranes. The results suggest that an experimental model in which premature labour is induced by the administration of cortisol to the foetus is probably incomplete, and that additional factors almost certainly contribute to the cascade phenomenon of spontaneous parturition.", "contents": "Ultrastructural changes in the placenta of the ewe following foetal infusion of cortisol. The placental changes which followed continuous infusion of cortisol into the sheep foetus in the later stages of gestation were, like the hormonal changes, broadly similar to those of spontaneous parturition. There was, however, a premature separation of foetal and maternal tissues in certain areas of the placental cotyledons, and this separation appeared to protect the foetal epithelium from the degenerative changes which normally take place in the short space of time between the birth of the lamb and the delivery of the foetal membranes. The results suggest that an experimental model in which premature labour is induced by the administration of cortisol to the foetus is probably incomplete, and that additional factors almost certainly contribute to the cascade phenomenon of spontaneous parturition."} {"id": "PMID:169541", "title": "Musculosketal symptoms and non-REM sleep disturbance in patients with \"fibrositis syndrome\" and healthy subjects.", "content": "In sleep studies of (a) patients with the \"fibrositis syndrome\" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpha-rhythms in the non-rapid-eye-movement (NREM) sleep EEG. This phenomenon has been termed alpha-delta sleep. In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of muscoloskeletal and mood symptoms comparable to the symptoms seen chronically in the patients. It is suggested that the external arousing stimulus, which induced alpha-delta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism. Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms. It is proposed that the \"fibrositis\" symptom complex be considered a \"non-restorative sleep syndrome\". Evidence froms presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms.", "contents": "Musculosketal symptoms and non-REM sleep disturbance in patients with \"fibrositis syndrome\" and healthy subjects. In sleep studies of (a) patients with the \"fibrositis syndrome\" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpha-rhythms in the non-rapid-eye-movement (NREM) sleep EEG. This phenomenon has been termed alpha-delta sleep. In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of muscoloskeletal and mood symptoms comparable to the symptoms seen chronically in the patients. It is suggested that the external arousing stimulus, which induced alpha-delta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism. Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms. It is proposed that the \"fibrositis\" symptom complex be considered a \"non-restorative sleep syndrome\". Evidence froms presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms."} {"id": "PMID:169550", "title": "A biochemical hypothesis to explain the mechanism of luteal regression.", "content": "It seems likely that luteal regression may involve a direct biochemical action of prostaglandin F2alpha (PGF2alpha) on the luteal cell since there are now several reports that PGF2alpha can directly inhibit steroidogenesis in vitro. However, the mechanism of such an action of PGF2alpha remains obscure. This article initially reviews the central role of adenosine 3,I5I-mono-phosphate (c-AMP) in initiating and maintaining the structural and functional changes occurring on luteinisation. A mechanism is suggested, supported by results obtained using granulosa cells in tissue culture, in which PGF2alpha initiates functional luteolysis by inhibiting further synthesis of c-AMP. This mechanism is then used in conjunction with further in vitro observations to provide a possible explanation for the inability of PGF2alpha to regress newly formed corpora lutea. Finally, the possible mechanisms of structural regression are discussed.", "contents": "A biochemical hypothesis to explain the mechanism of luteal regression. It seems likely that luteal regression may involve a direct biochemical action of prostaglandin F2alpha (PGF2alpha) on the luteal cell since there are now several reports that PGF2alpha can directly inhibit steroidogenesis in vitro. However, the mechanism of such an action of PGF2alpha remains obscure. This article initially reviews the central role of adenosine 3,I5I-mono-phosphate (c-AMP) in initiating and maintaining the structural and functional changes occurring on luteinisation. A mechanism is suggested, supported by results obtained using granulosa cells in tissue culture, in which PGF2alpha initiates functional luteolysis by inhibiting further synthesis of c-AMP. This mechanism is then used in conjunction with further in vitro observations to provide a possible explanation for the inability of PGF2alpha to regress newly formed corpora lutea. Finally, the possible mechanisms of structural regression are discussed."} {"id": "PMID:169551", "title": "Secretion rate of prostaglandin F during induced labor in goats.", "content": "Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.", "contents": "Secretion rate of prostaglandin F during induced labor in goats. Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest."} {"id": "PMID:169552", "title": "Compartive behavioral effects of dibutyryl cyclic AMP and prostaglandin E1 in mice.", "content": "Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to stuey the interaction of PGE1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE1 (0.01-5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. decreases in SLMA were produced by PGE1 (79%), DBcAMP (41%) and DBcAMP-PGE1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE1 or DBcAMP+PGE1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed.", "contents": "Compartive behavioral effects of dibutyryl cyclic AMP and prostaglandin E1 in mice. Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to stuey the interaction of PGE1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE1 (0.01-5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. decreases in SLMA were produced by PGE1 (79%), DBcAMP (41%) and DBcAMP-PGE1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE1 or DBcAMP+PGE1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed."} {"id": "PMID:169553", "title": "Structural requirements for the binding of prostaglandins.", "content": "The binding of prostaglandins and analogs to the lipocyte PGE receptor was shown to exhibit a high degree of structural specificity. Small changes, particulary at the 9-keto or 15-hydroxyl position, were found to drastically diminish interaction with the receptor. Studies of a rather substantial number of compounds revealed a close relationshio between affinity for the lipocyte PGE receptor and the ability to stimulate cyclic AMP synthesis in the isolated mouse ovary. In general, activities in these two parameters follow the biological potencies generally recognized for the compounds.", "contents": "Structural requirements for the binding of prostaglandins. The binding of prostaglandins and analogs to the lipocyte PGE receptor was shown to exhibit a high degree of structural specificity. Small changes, particulary at the 9-keto or 15-hydroxyl position, were found to drastically diminish interaction with the receptor. Studies of a rather substantial number of compounds revealed a close relationshio between affinity for the lipocyte PGE receptor and the ability to stimulate cyclic AMP synthesis in the isolated mouse ovary. In general, activities in these two parameters follow the biological potencies generally recognized for the compounds."} {"id": "PMID:169555", "title": "RNA synthesis by isolated Yoshida ascites hepatoma A.H. 130 cells mitochondria.", "content": "Mitochondria isolated from Yoshida ascites hepatoma A.H. 130 cells are able to incorporate 3H-UTP into RNA. The reaction has been extensively characterized and appear to be supported by a typical DNA-dependent RNA polymerase, and no special differences with the system of normal rat liver mitochondria have been found.", "contents": "RNA synthesis by isolated Yoshida ascites hepatoma A.H. 130 cells mitochondria. Mitochondria isolated from Yoshida ascites hepatoma A.H. 130 cells are able to incorporate 3H-UTP into RNA. The reaction has been extensively characterized and appear to be supported by a typical DNA-dependent RNA polymerase, and no special differences with the system of normal rat liver mitochondria have been found."} {"id": "PMID:169556", "title": "On the diuretic action produced dibutyryl cyclic AMP in dogs.", "content": "Experiments were undertaken on order to elucidate the mechanism of diuresis induced by dibutyryl cyclic AMP in dogs. Intravenous injections of dibutyryl cyclic AMP produced an increase in urine flow in dogs hydrated with saline. It was also noted that dibutyryl cyclic AMP produced an increase in myocardial contraction, renal blood flow and glomerular filtration rate; In addition, unilateral injection of dibutyryl cyclic AMP into the left renal artery produced diuresis bilaterally. Based on the above findings it was suggested that the diuretic action induced by dibutyryl cyclic AMP is associated with its hemodynamic effect.", "contents": "On the diuretic action produced dibutyryl cyclic AMP in dogs. Experiments were undertaken on order to elucidate the mechanism of diuresis induced by dibutyryl cyclic AMP in dogs. Intravenous injections of dibutyryl cyclic AMP produced an increase in urine flow in dogs hydrated with saline. It was also noted that dibutyryl cyclic AMP produced an increase in myocardial contraction, renal blood flow and glomerular filtration rate; In addition, unilateral injection of dibutyryl cyclic AMP into the left renal artery produced diuresis bilaterally. Based on the above findings it was suggested that the diuretic action induced by dibutyryl cyclic AMP is associated with its hemodynamic effect."} {"id": "PMID:169557", "title": "Technique of lymphography in the rat.", "content": "Most the lymphatic system in the rat was directly observed in our experiment by radiological means. The lymphatics of the limbs were firstly revealed by subcutaneous injection of Patent Blue V. Lipiodol was used as radio-opaque compound injected by a micro-technique fully described by the authors.", "contents": "Technique of lymphography in the rat. Most the lymphatic system in the rat was directly observed in our experiment by radiological means. The lymphatics of the limbs were firstly revealed by subcutaneous injection of Patent Blue V. Lipiodol was used as radio-opaque compound injected by a micro-technique fully described by the authors."} {"id": "PMID:169558", "title": "Vinblastine-induced ultrastructural changes in perisinusoidal cells of the rat liver.", "content": "Vinblastine, given intravenously to rats, leads to disappearance of microtubules, formation of paracrystalline inclusions and accumulation of fat droplets in the cytoplasm of the perisinusoidal cells of the liver suggesting that microtubules of the perisinusoidal cells play a role in lipid metabolism.", "contents": "Vinblastine-induced ultrastructural changes in perisinusoidal cells of the rat liver. Vinblastine, given intravenously to rats, leads to disappearance of microtubules, formation of paracrystalline inclusions and accumulation of fat droplets in the cytoplasm of the perisinusoidal cells of the liver suggesting that microtubules of the perisinusoidal cells play a role in lipid metabolism."} {"id": "PMID:169559", "title": "Comparison of the effects of vitamin D3, dihydrotachysterol, and parathormone on calcium kinetics in the rat.", "content": "Rats were treated with 100 I.U. (= 2.5 mcg) Vit. D3/day during 14 days and submitted to a radio-Calcium assay of Calcium kinetics. The results were compared with those obtained in weight-matched pair-fed controls, and with those obtained in former experiments applying dihydrotachysterol and parathormone. Vit. D3, which is transformed to a hormone, increased the fast exchange compartment, the exchange rate between the compartments, the endogenous fecal Calcium excretion rate, and the bone uptake and release rates. These findings indicate that the Vit. D-hormone is more similar in its action to the other hormone, parathormone, than to its close chemical relative dihydrotachysterol.", "contents": "Comparison of the effects of vitamin D3, dihydrotachysterol, and parathormone on calcium kinetics in the rat. Rats were treated with 100 I.U. (= 2.5 mcg) Vit. D3/day during 14 days and submitted to a radio-Calcium assay of Calcium kinetics. The results were compared with those obtained in weight-matched pair-fed controls, and with those obtained in former experiments applying dihydrotachysterol and parathormone. Vit. D3, which is transformed to a hormone, increased the fast exchange compartment, the exchange rate between the compartments, the endogenous fecal Calcium excretion rate, and the bone uptake and release rates. These findings indicate that the Vit. D-hormone is more similar in its action to the other hormone, parathormone, than to its close chemical relative dihydrotachysterol."} {"id": "PMID:169562", "title": "Heterodox practitioners and the availability of specialist advice.", "content": "The characteristics of the principal categories of more professional heterodox practice are examined. It is concluded that rheumatic diseases are one of the likeliest fields for conflcit between orthodox and fringe medicine. The distribution of manpower engaged in alternative systems of health care is compared with that of orthodox medical services. The limited data on utilization of unorthodox remedies are reviewed. Far from conflict ensuing, it is argued that dialogue must develop in order to submit procedures like manipulation to satisfactory clinical trial.", "contents": "Heterodox practitioners and the availability of specialist advice. The characteristics of the principal categories of more professional heterodox practice are examined. It is concluded that rheumatic diseases are one of the likeliest fields for conflcit between orthodox and fringe medicine. The distribution of manpower engaged in alternative systems of health care is compared with that of orthodox medical services. The limited data on utilization of unorthodox remedies are reviewed. Far from conflict ensuing, it is argued that dialogue must develop in order to submit procedures like manipulation to satisfactory clinical trial."} {"id": "PMID:169564", "title": "[Mixed tumors and cylindromas].", "content": "The lacrimals glands may be the focus of the pleomorphic tumours with the same property as the major and minor salivary glands. Their localisation causes different clinical and therapeutic consequences. The cylindromes or Adenoid Cystic Carcinoma are to be put on a parallel with the pleomorphic tumours, though the issue of the clinical evolution is very different for each of them.", "contents": "[Mixed tumors and cylindromas]. The lacrimals glands may be the focus of the pleomorphic tumours with the same property as the major and minor salivary glands. Their localisation causes different clinical and therapeutic consequences. The cylindromes or Adenoid Cystic Carcinoma are to be put on a parallel with the pleomorphic tumours, though the issue of the clinical evolution is very different for each of them."} {"id": "PMID:169566", "title": "Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of dietary manipulation.", "content": "To study the metabolism of the abnormal plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency we performed five dietary experiments designed to perturb their distribution and composition. Four patients with the disease were given successive diets that differed in triglyceride, carbohydrate, or cholestrol content, and after each dietary period the lipoproteins were analyzed by combinations of preparative and analytical ultracentrifugation, gel filtration, chromatography, and disc gel electrophorsis. Lowering the intake of long chain, dietary triglyceride descreased the concentrations of the large very low density lipoproteins, the large and intermediate low density lipoproteins, and the small high density lipoproteins by as much ad 79 %, but either increased or did not change the concentrations of the small very low and low density lipoproteins. Re-adding long chain triglycerdine to the diet generally reversed these effects, but increasing the dietary cholesterol without lowering the dietary triglyceride only decreased the concentration of plasma cholesteryl ester. We conclude that the concentrations of the large very low and low sensity lipoproteins, the intermediate-sized low density lipoproteins, and the small high density lipoproteins are related to the absorption and subsequent transport of long chain dietary fatty acids. Since these lipoproteins are rich in unesterified cholesterol and lecithin, two polar lipids that form a substantial part of the surfaces of chylomicrons, components of chylomicron surfaces may accumulate in the patient's plasma following enzymic removal of chylomicron triglyceride and contribute to several of the abnormal lipoproteins.", "contents": "Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of dietary manipulation. To study the metabolism of the abnormal plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency we performed five dietary experiments designed to perturb their distribution and composition. Four patients with the disease were given successive diets that differed in triglyceride, carbohydrate, or cholestrol content, and after each dietary period the lipoproteins were analyzed by combinations of preparative and analytical ultracentrifugation, gel filtration, chromatography, and disc gel electrophorsis. Lowering the intake of long chain, dietary triglyceride descreased the concentrations of the large very low density lipoproteins, the large and intermediate low density lipoproteins, and the small high density lipoproteins by as much ad 79 %, but either increased or did not change the concentrations of the small very low and low density lipoproteins. Re-adding long chain triglycerdine to the diet generally reversed these effects, but increasing the dietary cholesterol without lowering the dietary triglyceride only decreased the concentration of plasma cholesteryl ester. We conclude that the concentrations of the large very low and low sensity lipoproteins, the intermediate-sized low density lipoproteins, and the small high density lipoproteins are related to the absorption and subsequent transport of long chain dietary fatty acids. Since these lipoproteins are rich in unesterified cholesterol and lecithin, two polar lipids that form a substantial part of the surfaces of chylomicrons, components of chylomicron surfaces may accumulate in the patient's plasma following enzymic removal of chylomicron triglyceride and contribute to several of the abnormal lipoproteins."} {"id": "PMID:169567", "title": "Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of incubation with lecithin: cholesterol acyltransferase in vitro.", "content": "To study the effect of lecithin: cholesterol acyltransferase (LCAT) on the plasma lipoproteins of patients with familial LCAT deficiency, whole plasma or the lipoprotein fraction of d smaller than 1.006 g/ml (VLDL) was incubated in the presence of LCAT and subsequently examined by chemical, physical, and immunological techniques. The following occured upon incubating either hyperlipemic or nonlipemic plasma: The concentrations of polar lipids decreased, particulary in the large molecular weight lipoprotein subfraction of d 1.019-1.063 g/ml (LDL2) and in the lipoprotein fraction of 1.06301.25 g/ml (HDL). The concentration of cholesteryl ester (CE) increased, particularly in the VLDL and in the lipoprotein fractions of d 1.006-1.019 g/ml (LDL1) and LDL2. The concentration of arginine-rich apolipoprotein decreased in the HDL and increased in the VLDL and LDL1. The concentrations of the C-apoliproteins appeared to change in the opposite direction. The concentration of apolipoprotein B in the LDL increased concomitantly with an increase in the concentration and flotation rsate of the small LDL2. The concentration apolipoprotein A-I in the HDL increased; and a major component in the HDL fraction became identical in apperance to normal HDL. Upon incubating a patient's isolated VLDL in the presence of LCAT, lipoproteins with properties similar to normal LDL2 were formed. These experiments show that the LCAT reaction can alter the apolipoprotein content and physical properties as well as the lipid content of the patient's lipoproteins.", "contents": "Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of incubation with lecithin: cholesterol acyltransferase in vitro. To study the effect of lecithin: cholesterol acyltransferase (LCAT) on the plasma lipoproteins of patients with familial LCAT deficiency, whole plasma or the lipoprotein fraction of d smaller than 1.006 g/ml (VLDL) was incubated in the presence of LCAT and subsequently examined by chemical, physical, and immunological techniques. The following occured upon incubating either hyperlipemic or nonlipemic plasma: The concentrations of polar lipids decreased, particulary in the large molecular weight lipoprotein subfraction of d 1.019-1.063 g/ml (LDL2) and in the lipoprotein fraction of 1.06301.25 g/ml (HDL). The concentration of cholesteryl ester (CE) increased, particularly in the VLDL and in the lipoprotein fractions of d 1.006-1.019 g/ml (LDL1) and LDL2. The concentration of arginine-rich apolipoprotein decreased in the HDL and increased in the VLDL and LDL1. The concentrations of the C-apoliproteins appeared to change in the opposite direction. The concentration of apolipoprotein B in the LDL increased concomitantly with an increase in the concentration and flotation rsate of the small LDL2. The concentration apolipoprotein A-I in the HDL increased; and a major component in the HDL fraction became identical in apperance to normal HDL. Upon incubating a patient's isolated VLDL in the presence of LCAT, lipoproteins with properties similar to normal LDL2 were formed. These experiments show that the LCAT reaction can alter the apolipoprotein content and physical properties as well as the lipid content of the patient's lipoproteins."} {"id": "PMID:169571", "title": "[Encapsulating peri-hepatitis. Apropos of 4 cases].", "content": "The authors report 4 cases of encapsulating peri-hepatitis, including an angiographic study. Selective arteriography of the coeliac trunk showed extremely sinuous intra-hepatic arteries in 3 of these cases, and obstruction of the portal vein, in one case. Catheterisation of the hepatic veins showed a pressure gradient between the obstructed hepatic vein and the free supra-hepatic pressure, showing a post-sinusoidal block. In 2 of the 4 cases, ascites was chylous. Lymphography carried out via lymphatics in the foot was negative in 3 cases where it was carried out. One case showed, on two successive laparoscopies, that micro-nodular cirrhosis was present before the development of encapsulating peri-hepatitis.", "contents": "[Encapsulating peri-hepatitis. Apropos of 4 cases]. The authors report 4 cases of encapsulating peri-hepatitis, including an angiographic study. Selective arteriography of the coeliac trunk showed extremely sinuous intra-hepatic arteries in 3 of these cases, and obstruction of the portal vein, in one case. Catheterisation of the hepatic veins showed a pressure gradient between the obstructed hepatic vein and the free supra-hepatic pressure, showing a post-sinusoidal block. In 2 of the 4 cases, ascites was chylous. Lymphography carried out via lymphatics in the foot was negative in 3 cases where it was carried out. One case showed, on two successive laparoscopies, that micro-nodular cirrhosis was present before the development of encapsulating peri-hepatitis."} {"id": "PMID:169572", "title": "[Cytogenetic study of 30 couples having had several spontaneous abortions].", "content": "In 30 couples consulting after two or more failed pregnancies, the authors detected two women with reciprocal translocation in the heterozygous condition: t (5 ; 6) (q 35 ; q 21) in one case. t (5 ; 10) (q 15 ; q 25) in the other case. In both cases, there was, later, birth of a normal boy of karyotype 46, XY. It thus appears obvious that the balanced structural changes which occur in the fertility of these couples, reduces the latter.", "contents": "[Cytogenetic study of 30 couples having had several spontaneous abortions]. In 30 couples consulting after two or more failed pregnancies, the authors detected two women with reciprocal translocation in the heterozygous condition: t (5 ; 6) (q 35 ; q 21) in one case. t (5 ; 10) (q 15 ; q 25) in the other case. In both cases, there was, later, birth of a normal boy of karyotype 46, XY. It thus appears obvious that the balanced structural changes which occur in the fertility of these couples, reduces the latter."} {"id": "PMID:169573", "title": "[Radiologic study of gastric transit after ingestion of natural soda water].", "content": "Is a barium meal modified when soda water is used as a drink? In a series of 60 patients, the authors studied radiologically, a barium meal after taking ordinary tap water and after taking soda water. They observed after taking soda water, an increase in volume of the air pocket at the upper end of the stomach with, in 69% of cases, return to normal within 10 minutes. Gastric emptying occurred more rapidly with soda water in 40% of cases, and identically in 30% of cases.", "contents": "[Radiologic study of gastric transit after ingestion of natural soda water]. Is a barium meal modified when soda water is used as a drink? In a series of 60 patients, the authors studied radiologically, a barium meal after taking ordinary tap water and after taking soda water. They observed after taking soda water, an increase in volume of the air pocket at the upper end of the stomach with, in 69% of cases, return to normal within 10 minutes. Gastric emptying occurred more rapidly with soda water in 40% of cases, and identically in 30% of cases."} {"id": "PMID:169574", "title": "[Pathology of peripheral nerves (elementary lesions, their development and different types of neuropathies) (1st part)].", "content": "The ultrastructural features of the normal components of the endoneurium are described. The sequence of events of axonal (wallerian) and segmental demyelination are enumerated. The process of ageing in the peripheral nervous system is analysed.", "contents": "[Pathology of peripheral nerves (elementary lesions, their development and different types of neuropathies) (1st part)]. The ultrastructural features of the normal components of the endoneurium are described. The sequence of events of axonal (wallerian) and segmental demyelination are enumerated. The process of ageing in the peripheral nervous system is analysed."} {"id": "PMID:169577", "title": "[Arrector muscle in patients with scleroderma. Histological and histo-enzymological study].", "content": "In a previous paper, we have found, at post-mortem examination of three cases of scleroderma, the oesophageal smooth muscle alterations already predicted by physiologists and reported by Treacy. These lesions mostly consist of a loss of the staining properties of the differenciated cytoplasm of the muscle cell, preceding any appearance of interstitial fibrosis. We have already reported these muscle lesions at all other levels of the digestive tract (stomach, small and large bowels), and also in the bladder muscle. In the present study, we have attempted to precise these notions in biopsies and have studied the arrector pili muscles in normal skin of 13 sclerodermic patients by means of histochemical (Regaud, Mallory, etc. ...) and enzyme stains. In all cases, we have been able to identify morphological alterations of the muscle fiber, mostly consisting in an irregular pattern of enzyme properties, especially when diaphorases, dehydrogenases and ATP ases were concerned. This work seems to confirm that the primary site of the sclerodermal lesions is situated in the smooth muscle fiber.", "contents": "[Arrector muscle in patients with scleroderma. Histological and histo-enzymological study]. In a previous paper, we have found, at post-mortem examination of three cases of scleroderma, the oesophageal smooth muscle alterations already predicted by physiologists and reported by Treacy. These lesions mostly consist of a loss of the staining properties of the differenciated cytoplasm of the muscle cell, preceding any appearance of interstitial fibrosis. We have already reported these muscle lesions at all other levels of the digestive tract (stomach, small and large bowels), and also in the bladder muscle. In the present study, we have attempted to precise these notions in biopsies and have studied the arrector pili muscles in normal skin of 13 sclerodermic patients by means of histochemical (Regaud, Mallory, etc. ...) and enzyme stains. In all cases, we have been able to identify morphological alterations of the muscle fiber, mostly consisting in an irregular pattern of enzyme properties, especially when diaphorases, dehydrogenases and ATP ases were concerned. This work seems to confirm that the primary site of the sclerodermal lesions is situated in the smooth muscle fiber."} {"id": "PMID:169578", "title": "[Ultrastructural study of the arrector muscle in the patient with scleroderma. Preliminary analysis apropos of 3 cases].", "content": "An electron microscope study of the arrector pili muscle, using biopsies obtained from clinically and histologically healthy skin in 3 cases of scleroderma, showed the primary origin of the muscle disorders. They showed a certain number of changes, both of the differentiated cytoplasm and of the common cytoplasm.", "contents": "[Ultrastructural study of the arrector muscle in the patient with scleroderma. Preliminary analysis apropos of 3 cases]. An electron microscope study of the arrector pili muscle, using biopsies obtained from clinically and histologically healthy skin in 3 cases of scleroderma, showed the primary origin of the muscle disorders. They showed a certain number of changes, both of the differentiated cytoplasm and of the common cytoplasm."} {"id": "PMID:169579", "title": "[Psychosomatic study of duodenal ulcers in young adults in the military].", "content": "The authors report the relationship between psychological disturbances and duodenal ulcer, and discuss the conclusions of three studies carried out in military personnel. The group of young adults during war time, permitted them to analyse the role of psychological trauma in the onset and relapse of this disease. In young soldiers during peace time, there was significant affective immaturity. Finally, a study of young adults before call up, permitted comparison with military personnel. Rather than a study of specific characteristics, it appears that one should consider their dynamic organisation in order to understand the onset of symptoms.", "contents": "[Psychosomatic study of duodenal ulcers in young adults in the military]. The authors report the relationship between psychological disturbances and duodenal ulcer, and discuss the conclusions of three studies carried out in military personnel. The group of young adults during war time, permitted them to analyse the role of psychological trauma in the onset and relapse of this disease. In young soldiers during peace time, there was significant affective immaturity. Finally, a study of young adults before call up, permitted comparison with military personnel. Rather than a study of specific characteristics, it appears that one should consider their dynamic organisation in order to understand the onset of symptoms."} {"id": "PMID:169581", "title": "[Pathology of the peripheral nerve. (Teasing, the various degrees of denervation, onion bulbs) (2nd part)].", "content": "Anatomical data for the interpretation of teased fibres are described. The different degrees of degeneration in a peripheral neuropathy are enumerated and criteria to identify them are given. The onion bulb formation process is analysed and some morphologically different types are proposed.", "contents": "[Pathology of the peripheral nerve. (Teasing, the various degrees of denervation, onion bulbs) (2nd part)]. Anatomical data for the interpretation of teased fibres are described. The different degrees of degeneration in a peripheral neuropathy are enumerated and criteria to identify them are given. The onion bulb formation process is analysed and some morphologically different types are proposed."} {"id": "PMID:169582", "title": "[Muscular disorders of the patient with scleroderma. Clinical study].", "content": "In scleroderma, the scapular striated muscles may be affected showing rapid fatigability, and sometimes, muscle wasting with EMG changes. The smooth muscle changes, well known in the esophagus, where they lead to loss of peristalsis, may also be marked in other parts of the digestive tract. They lead to various symptoms, such as cramps, vomiting and diarrhea.", "contents": "[Muscular disorders of the patient with scleroderma. Clinical study]. In scleroderma, the scapular striated muscles may be affected showing rapid fatigability, and sometimes, muscle wasting with EMG changes. The smooth muscle changes, well known in the esophagus, where they lead to loss of peristalsis, may also be marked in other parts of the digestive tract. They lead to various symptoms, such as cramps, vomiting and diarrhea."} {"id": "PMID:169583", "title": "[Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis].", "content": "The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of \"metacritical aggravation\" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct.", "contents": "[Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis]. The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of \"metacritical aggravation\" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct."} {"id": "PMID:169584", "title": "[Bone metastases of colonic and rectal neoplasms. Apropos of 11 cases].", "content": "The authors report 11 personal cases and discuss the characteristics of bony metastases in carcinoma of the colon and rectum. The frequency of these metastases is fairly low (1.3% of all cases of bony metastases) as tumours of the large intestine do not tend to migrate to the bones. Sometimes bony metastases are the presenting symptom but, usually the metastases occur within 5 years of the diagnosis of the primary tumour. The clinical picture shows no special characteristics. Radiologically, these bony metastases may be either single or multiple. Their distribution recalls that of other metastases in the bones with a few differences, however. The special frequence of pelvic involvement, distal localisations (hands or feet) are not exceptional. Metastases usually give rise to osteolysis. The mixed appearances are, however, not rare, and usually give a pseudo-sarcomatous appearance, with invasion of the soft parts and very marked periosteal reaction. Sometimes, bony condensation may be noted. The treatment of rectal and colonic cancer with bony metastases, is disappointing as the disease is always fatal within a relatively short period, usually less than one year after the diagnosis of the bone involvement. The histological appearances of the bony lesions depend on differenciation of the tumour and the characteristics of the neighbouring bony abnormalities which, in our experience, usually include both osteolysis and osteogenesis.", "contents": "[Bone metastases of colonic and rectal neoplasms. Apropos of 11 cases]. The authors report 11 personal cases and discuss the characteristics of bony metastases in carcinoma of the colon and rectum. The frequency of these metastases is fairly low (1.3% of all cases of bony metastases) as tumours of the large intestine do not tend to migrate to the bones. Sometimes bony metastases are the presenting symptom but, usually the metastases occur within 5 years of the diagnosis of the primary tumour. The clinical picture shows no special characteristics. Radiologically, these bony metastases may be either single or multiple. Their distribution recalls that of other metastases in the bones with a few differences, however. The special frequence of pelvic involvement, distal localisations (hands or feet) are not exceptional. Metastases usually give rise to osteolysis. The mixed appearances are, however, not rare, and usually give a pseudo-sarcomatous appearance, with invasion of the soft parts and very marked periosteal reaction. Sometimes, bony condensation may be noted. The treatment of rectal and colonic cancer with bony metastases, is disappointing as the disease is always fatal within a relatively short period, usually less than one year after the diagnosis of the bone involvement. The histological appearances of the bony lesions depend on differenciation of the tumour and the characteristics of the neighbouring bony abnormalities which, in our experience, usually include both osteolysis and osteogenesis."} {"id": "PMID:169585", "title": "[Abnormalities of lumbar transverse processes].", "content": "The transverse processes of the lumbar vertebrae sometimes present rare abnormalities, or major abnormalities, which may be contrasted with congenital lesions concerning their volume, shape and direction. After a rapid review of the general and clinical characteristics, radiological analysis of the 59 cases collected in the literature and 6 personal cases, permits a provisional classification of the three varieties of lesion encountered. Apart from the rareness of cases known up to now, the interest of this study is to attract attention to the etiology which is still unknown, whether congenital or traumatic, and consequently, to the possible medico-legal consequences. Once again, as in other fields, the authors attract attention to the undoubted advantages of routine XRay of the lumbar spine and of the sacral area, one of which may be to discover the true etiology of the abnormalities encountered.", "contents": "[Abnormalities of lumbar transverse processes]. The transverse processes of the lumbar vertebrae sometimes present rare abnormalities, or major abnormalities, which may be contrasted with congenital lesions concerning their volume, shape and direction. After a rapid review of the general and clinical characteristics, radiological analysis of the 59 cases collected in the literature and 6 personal cases, permits a provisional classification of the three varieties of lesion encountered. Apart from the rareness of cases known up to now, the interest of this study is to attract attention to the etiology which is still unknown, whether congenital or traumatic, and consequently, to the possible medico-legal consequences. Once again, as in other fields, the authors attract attention to the undoubted advantages of routine XRay of the lumbar spine and of the sacral area, one of which may be to discover the true etiology of the abnormalities encountered."} {"id": "PMID:169586", "title": "[Various clinical aspects of cutaneous leishmaniasis, a disease too often unrecognized in the Paris area. Diagnostic and therapeutic problems].", "content": "Muco-cutaneous leishmaniasis is now more frequently observed in France owing to population movements. One should learn to recognise the disease, the various aspects of which are presented here (7 cases). They recall the necessity of associating direct search for leishmania in the serous exsudate from the lesions or on histological sections, routine culture of swabs on agar jelly en riched with blood and on heart-brain blood medium. The immunoglobulin estimation sometimes revealed significant increase in their levels, but the sero-immunologic reactions by the indirect immuno-fluorescent method, were all negative. The best treatment is N-methylglucamine antimoniate by intradermal injection under the lesions or, in some cases, the parenteral route. On the other hand, metronidazole does not seem to be efficacious in skin leishmaniasis in this part of the world.", "contents": "[Various clinical aspects of cutaneous leishmaniasis, a disease too often unrecognized in the Paris area. Diagnostic and therapeutic problems]. Muco-cutaneous leishmaniasis is now more frequently observed in France owing to population movements. One should learn to recognise the disease, the various aspects of which are presented here (7 cases). They recall the necessity of associating direct search for leishmania in the serous exsudate from the lesions or on histological sections, routine culture of swabs on agar jelly en riched with blood and on heart-brain blood medium. The immunoglobulin estimation sometimes revealed significant increase in their levels, but the sero-immunologic reactions by the indirect immuno-fluorescent method, were all negative. The best treatment is N-methylglucamine antimoniate by intradermal injection under the lesions or, in some cases, the parenteral route. On the other hand, metronidazole does not seem to be efficacious in skin leishmaniasis in this part of the world."} {"id": "PMID:169587", "title": "[Suppurative trichophytosis of animal origin. Apropos of 38 recent cases].", "content": "This study of 38 cases observed over a period of 7 years emphasizes the constancy of rural contamination, whether professional or not. An enquiry carried out among veterinary surgeons in this region, showed the increasing frequency of the animal infection particularly in young oxen, hence the increased risk of kerions. The author recalls the clinical description of kerion of the scalp in children and sycosis barbae in adults, in which one may also encounter folliculitis of the limbs. The parasite isolated, included various strains of Trichophyton, e.g., Trichophyton Trimentagrophytes, Tr. verrucosum and, more rarely, Tr. magnini. On the other hand, bacteriological examination was usually negative, there were only two cases of secondary staphylococcal infection. The authors emphasize their concept of the disease which is probably an immune process. Finally, rather than the usual treatment, they emphasize the possibilities of social re-insertion; the disease should be recognised as an occupational disease.", "contents": "[Suppurative trichophytosis of animal origin. Apropos of 38 recent cases]. This study of 38 cases observed over a period of 7 years emphasizes the constancy of rural contamination, whether professional or not. An enquiry carried out among veterinary surgeons in this region, showed the increasing frequency of the animal infection particularly in young oxen, hence the increased risk of kerions. The author recalls the clinical description of kerion of the scalp in children and sycosis barbae in adults, in which one may also encounter folliculitis of the limbs. The parasite isolated, included various strains of Trichophyton, e.g., Trichophyton Trimentagrophytes, Tr. verrucosum and, more rarely, Tr. magnini. On the other hand, bacteriological examination was usually negative, there were only two cases of secondary staphylococcal infection. The authors emphasize their concept of the disease which is probably an immune process. Finally, rather than the usual treatment, they emphasize the possibilities of social re-insertion; the disease should be recognised as an occupational disease."} {"id": "PMID:169588", "title": "[Anti-nuclear antibodies in collagen diseases].", "content": "The authors sought serum antinuclear antibodies by the indirect immunofluorescent method in 3,260 patients, and found these antibodies in 293 of them. 90 patients had a level equal or greater than 1/50. Among the latter, 54 had some form of collagen disease. The following facts are emphasized: -- antinuclear antibodies are always present in lupus erythematosus. Their levels fall under the influence of treatment when nephritis occurs; -- their frequency is greater (13 cases out of 16) during scleroderma, with often a hazy appearance; -- they are lower during rheumatoid arthritis (23% of cases had a significant level), and their presence is not a sign of worse prognosis; -- they were absent in other forms of collagen diseases.", "contents": "[Anti-nuclear antibodies in collagen diseases]. The authors sought serum antinuclear antibodies by the indirect immunofluorescent method in 3,260 patients, and found these antibodies in 293 of them. 90 patients had a level equal or greater than 1/50. Among the latter, 54 had some form of collagen disease. The following facts are emphasized: -- antinuclear antibodies are always present in lupus erythematosus. Their levels fall under the influence of treatment when nephritis occurs; -- their frequency is greater (13 cases out of 16) during scleroderma, with often a hazy appearance; -- they are lower during rheumatoid arthritis (23% of cases had a significant level), and their presence is not a sign of worse prognosis; -- they were absent in other forms of collagen diseases."} {"id": "PMID:169589", "title": "[Salmonellosis: retrospective study of 136 cases hospitalized at the C.H.U. of Tours].", "content": "136 cases of salmonellosis were seen in the Tours Hospital Center from 1965 to 1971. Salmonella typhi produced 32 cases of typhoid fever and 2 focal infections: a bacterial pleural effusion and an osteoarthritis. Salmonella para B induced 16 cases of typhoid fever. All these 50 patients were given chloramphenicol that was effective in vitro and in vivo as well. They usually exhibited very few and mild signs or symptoms but long lasting fever. Complications were very rare. There was no death. Paradoxically, the 86 \"minor\" salmonellosis (i.e. caused by other Salmonella species than S. typhi, S. paratyphi A, B or C) exhibited a much more overt symptomatology. Though all the \"major\" salmonellosis occurred in previously healthy patients and caused no death, the \"minor\" salmonellosis occurred mostly in seriously ill patients and had a lethal outcome for 5 out of 86. There was no typhoid fever epidemic in Touraine during recent years. Lysotyping ruled out the hypothesis of an endemic local reservoir. On the other hand, two hospital outbreaks of \"minor\" salmonellosis were recognized: one in a psychiatric ward due to S. java in 1967, the other in a pediatric ward due to S. wien in 1971-1972 respectively.", "contents": "[Salmonellosis: retrospective study of 136 cases hospitalized at the C.H.U. of Tours]. 136 cases of salmonellosis were seen in the Tours Hospital Center from 1965 to 1971. Salmonella typhi produced 32 cases of typhoid fever and 2 focal infections: a bacterial pleural effusion and an osteoarthritis. Salmonella para B induced 16 cases of typhoid fever. All these 50 patients were given chloramphenicol that was effective in vitro and in vivo as well. They usually exhibited very few and mild signs or symptoms but long lasting fever. Complications were very rare. There was no death. Paradoxically, the 86 \"minor\" salmonellosis (i.e. caused by other Salmonella species than S. typhi, S. paratyphi A, B or C) exhibited a much more overt symptomatology. Though all the \"major\" salmonellosis occurred in previously healthy patients and caused no death, the \"minor\" salmonellosis occurred mostly in seriously ill patients and had a lethal outcome for 5 out of 86. There was no typhoid fever epidemic in Touraine during recent years. Lysotyping ruled out the hypothesis of an endemic local reservoir. On the other hand, two hospital outbreaks of \"minor\" salmonellosis were recognized: one in a psychiatric ward due to S. java in 1967, the other in a pediatric ward due to S. wien in 1971-1972 respectively."} {"id": "PMID:169593", "title": "Antimicrobial susceptibility of clinical isolates of gram-negative bacilli.", "content": "No one can doubt the increased incidence of gram-negative bacillary infections and the importance of an awareness of this increase. Today's hospital, where one finds aggressive surgery, patients with multiple indwelling polyethylene lines and Foley catheters, and widespread use of prophylactic antibiotics, serves as a haven for resistant gram-negative bacilli. Twenty-five strains of Escherichia coli, Klebsiella sp, Enterobacter sp, Pseudomonas sp, indole-negative Proteus sp, indole-positive Proteus sp, and Serratia sp from hospitalized patients were tested for susceptibility to eight commonly used antibiotics using an inocula replicating method. Gentamicin proved to be the most effective antibiotic against the majority; most strains were inhibited by 3.12mug/ml or less. Other antibiotics, although not so active against all species, were effective against selected species.", "contents": "Antimicrobial susceptibility of clinical isolates of gram-negative bacilli. No one can doubt the increased incidence of gram-negative bacillary infections and the importance of an awareness of this increase. Today's hospital, where one finds aggressive surgery, patients with multiple indwelling polyethylene lines and Foley catheters, and widespread use of prophylactic antibiotics, serves as a haven for resistant gram-negative bacilli. Twenty-five strains of Escherichia coli, Klebsiella sp, Enterobacter sp, Pseudomonas sp, indole-negative Proteus sp, indole-positive Proteus sp, and Serratia sp from hospitalized patients were tested for susceptibility to eight commonly used antibiotics using an inocula replicating method. Gentamicin proved to be the most effective antibiotic against the majority; most strains were inhibited by 3.12mug/ml or less. Other antibiotics, although not so active against all species, were effective against selected species."} {"id": "PMID:169594", "title": "Carotid-cavernous fistula: a complication of maxillofacial trauma.", "content": "Fistulas of the internal carotid-cavernous sinus are an unusual arteriovenous malformation. Two types exist: (1) spontaneous fistulas and (2) traumatic fistulas. This paper deals with the traumatic variety which is seen more commonly in men as a direct result of severe maxillofacial injury. Recent anatomic studies are correlated with the physical findings associated with carotid-cavernous fistula, ie, headache, chemosis, exophthalmos, pulsatile bruit, and multiple cranial nerve paralyses. A case report illustrates these findings. The differential diagnosis which varies from tumors, to cavernous sinus thrombosis, to intraorbital aneurysm is discussed. The role of angiography in diagnosis is described. Present management consists of intracranial ligation of the internal carotid artery with use of a muscle embolus to occlude the fistula and selective ligation of the cervical carotid.", "contents": "Carotid-cavernous fistula: a complication of maxillofacial trauma. Fistulas of the internal carotid-cavernous sinus are an unusual arteriovenous malformation. Two types exist: (1) spontaneous fistulas and (2) traumatic fistulas. This paper deals with the traumatic variety which is seen more commonly in men as a direct result of severe maxillofacial injury. Recent anatomic studies are correlated with the physical findings associated with carotid-cavernous fistula, ie, headache, chemosis, exophthalmos, pulsatile bruit, and multiple cranial nerve paralyses. A case report illustrates these findings. The differential diagnosis which varies from tumors, to cavernous sinus thrombosis, to intraorbital aneurysm is discussed. The role of angiography in diagnosis is described. Present management consists of intracranial ligation of the internal carotid artery with use of a muscle embolus to occlude the fistula and selective ligation of the cervical carotid."} {"id": "PMID:169598", "title": "Hypercholesterolaemia in primary cancer of the liver.", "content": "Hepatic synthesis of cholesterol in higher animals is normally markedly suppressed by dietary cholesterol. This feedback regulation has been shown to be absent in all experimental hepatomas studied, and also in the only 2 humans with primary hepatocellular cancer (PHC) who have been investigated. Another patient who presented with hypercholesterolaemia is described in whom cholesterogenesis in the tumour was not suppressed by cholesterol feeding. In order to determine the frequency with which hypercholesterolaemia occurs in PHC, serum cholesterol levels were measured in 132 Black patients with this tumour. Raised levels were found in 14 of the patients (11%). In only 2 of these was hypercholesterolaemia associated with obstructive jaundice.", "contents": "Hypercholesterolaemia in primary cancer of the liver. Hepatic synthesis of cholesterol in higher animals is normally markedly suppressed by dietary cholesterol. This feedback regulation has been shown to be absent in all experimental hepatomas studied, and also in the only 2 humans with primary hepatocellular cancer (PHC) who have been investigated. Another patient who presented with hypercholesterolaemia is described in whom cholesterogenesis in the tumour was not suppressed by cholesterol feeding. In order to determine the frequency with which hypercholesterolaemia occurs in PHC, serum cholesterol levels were measured in 132 Black patients with this tumour. Raised levels were found in 14 of the patients (11%). In only 2 of these was hypercholesterolaemia associated with obstructive jaundice."} {"id": "PMID:169600", "title": "The potential for carcinoma existing synchronously on a microscopic level within the second breast.", "content": "In the present study, 23 of 314 patients presented with asymptomatic lesions in the second breast, comparing favorably with the incidence of asymptomatic carcinomas of the second breast reported in other series. The type of biopys used appears important, most surgeons advocating resection of a segment of breast ranging from 20 to 30 per cent of the quadrant being sampled. It appears that treatment of carcinoma of the second breast is essentially curative when the lesion is not noted clinically. Adequate treatment of the second breast lesion appears to reduce the at risk group within the second breast. It is usually stated that 10 per cent of patients will have a second carcinoma of the breast develop. In this study, metachronous lesions developed in six of 291 patients. Considering that these tumors all recurred in the outer quadrant of the remaining breast, the possibility arises that it may be more productive to do all biopsies in the tail of the second breast rather than to perform the so-called mirror image biopsy that was used in the present study. Results from this and other studies do appear to indicate that the utilization of a mirror image biopsy or outer quadrant biopsy is an effective way to detect and treat occult malignant tumors as well as the earliest forms of premalignant disease.", "contents": "The potential for carcinoma existing synchronously on a microscopic level within the second breast. In the present study, 23 of 314 patients presented with asymptomatic lesions in the second breast, comparing favorably with the incidence of asymptomatic carcinomas of the second breast reported in other series. The type of biopys used appears important, most surgeons advocating resection of a segment of breast ranging from 20 to 30 per cent of the quadrant being sampled. It appears that treatment of carcinoma of the second breast is essentially curative when the lesion is not noted clinically. Adequate treatment of the second breast lesion appears to reduce the at risk group within the second breast. It is usually stated that 10 per cent of patients will have a second carcinoma of the breast develop. In this study, metachronous lesions developed in six of 291 patients. Considering that these tumors all recurred in the outer quadrant of the remaining breast, the possibility arises that it may be more productive to do all biopsies in the tail of the second breast rather than to perform the so-called mirror image biopsy that was used in the present study. Results from this and other studies do appear to indicate that the utilization of a mirror image biopsy or outer quadrant biopsy is an effective way to detect and treat occult malignant tumors as well as the earliest forms of premalignant disease."} {"id": "PMID:169604", "title": "[The incidence of lymphosarcoma (leukaemia) and feline leukaemia virus (FeLV) in cats in the Netherlands (author's transl)].", "content": "Seven different groups of cats were examined to study the incidence and distribution of feline leukaemia virus (FeLV) in the Netherlands. The indirect fluorescent antibody (IFA) technique was used to detect FeLV antigen. Of the cats with lymphosarcoma (leukaemia), 73.2 per cent and of those with infectious peritonitis, 32.4 per cent were found to be positive for FeLV antigen. Of the sixty-six cats with other tumours, only one, a cat with carcinoma of the mammary gland; was positive for FeLV antigen. Of 557 cats with various lesions, forty-two (7.5 percent) were positive for FeLV antigen. The IFA-test was found to be a useful adjunct in establishing the correct diagnosis. Of all stud cats which had been in contact with FeLV-positive cats, 24.7 percent were positive for FeLV antigen, wheras all those which had not been in contact with these cats, were negative. There was a marked difference between the proportions of FeLV-positive cats in the groups of clinically normal cats which had (20.6 per cent) and which had not (0.4 per cent) been in contact with FeLV-positive cats. Follow-up studies showed that 67.8 percent of the clinically normal, FeLV-positive cats had died from or been sacrificed because of FeLV-associated diseases within twenty months.", "contents": "[The incidence of lymphosarcoma (leukaemia) and feline leukaemia virus (FeLV) in cats in the Netherlands (author's transl)]. Seven different groups of cats were examined to study the incidence and distribution of feline leukaemia virus (FeLV) in the Netherlands. The indirect fluorescent antibody (IFA) technique was used to detect FeLV antigen. Of the cats with lymphosarcoma (leukaemia), 73.2 per cent and of those with infectious peritonitis, 32.4 per cent were found to be positive for FeLV antigen. Of the sixty-six cats with other tumours, only one, a cat with carcinoma of the mammary gland; was positive for FeLV antigen. Of 557 cats with various lesions, forty-two (7.5 percent) were positive for FeLV antigen. The IFA-test was found to be a useful adjunct in establishing the correct diagnosis. Of all stud cats which had been in contact with FeLV-positive cats, 24.7 percent were positive for FeLV antigen, wheras all those which had not been in contact with these cats, were negative. There was a marked difference between the proportions of FeLV-positive cats in the groups of clinically normal cats which had (20.6 per cent) and which had not (0.4 per cent) been in contact with FeLV-positive cats. Follow-up studies showed that 67.8 percent of the clinically normal, FeLV-positive cats had died from or been sacrificed because of FeLV-associated diseases within twenty months."} {"id": "PMID:169605", "title": "[Pathological anatomy of the malformation of the lung (author's transl)].", "content": "With short sidelights to embryology a survey of clinically important malformations of the airways, respiratory tissue, and vessels is given and their differential diagnosis with similiar acquired lesions discussed.", "contents": "[Pathological anatomy of the malformation of the lung (author's transl)]. With short sidelights to embryology a survey of clinically important malformations of the airways, respiratory tissue, and vessels is given and their differential diagnosis with similiar acquired lesions discussed."} {"id": "PMID:169610", "title": "The effect of agents which modulate levels of the cyclic nucleotides on human lymphotoxin secretion and activity in vitro.", "content": "The ability of concanavalin-A (Con-A) to activate lymphocytes to secrete human lymphotoxin (LT) was tested in the presence of agents known to modify the intracellular levels of cyclic nucleotides (cAMP and cGMP). Lymphocytes were treated with these agents at different stages of activation: (1) during the first encounter with mitogens, and (2) after they had been fully activated and were restimulated. Two agents, Dibutyryl cAMP and theophylline, dramatically inhibit the amount of LT secreted during both \"primary\" and \"secondary\" activation by Con-A. In contrast; DL-isoproterenol had a weak effect during primary activation, but greatly reduced the level of LT secreted during secondary activation. Agents which affect the intracellular level of cGMP were also tested. Imidazole had no effect on LT secretion by either primary or secondary Con-A activated cells. In contrast, carbamyl choline greatly reduced LT secretion to a level comparable to Dibutyryl cAMP and theophylline. All agents tested protected, to some degree, the sensitive alpha-L cell against LT-induced destruction in vitro. Agents which affect the levels of cyclic nucleotides affect both the effectiveness of the aggressor cell and the sensitivity of the target cells in vitro.", "contents": "The effect of agents which modulate levels of the cyclic nucleotides on human lymphotoxin secretion and activity in vitro. The ability of concanavalin-A (Con-A) to activate lymphocytes to secrete human lymphotoxin (LT) was tested in the presence of agents known to modify the intracellular levels of cyclic nucleotides (cAMP and cGMP). Lymphocytes were treated with these agents at different stages of activation: (1) during the first encounter with mitogens, and (2) after they had been fully activated and were restimulated. Two agents, Dibutyryl cAMP and theophylline, dramatically inhibit the amount of LT secreted during both \"primary\" and \"secondary\" activation by Con-A. In contrast; DL-isoproterenol had a weak effect during primary activation, but greatly reduced the level of LT secreted during secondary activation. Agents which affect the intracellular level of cGMP were also tested. Imidazole had no effect on LT secretion by either primary or secondary Con-A activated cells. In contrast, carbamyl choline greatly reduced LT secretion to a level comparable to Dibutyryl cAMP and theophylline. All agents tested protected, to some degree, the sensitive alpha-L cell against LT-induced destruction in vitro. Agents which affect the levels of cyclic nucleotides affect both the effectiveness of the aggressor cell and the sensitivity of the target cells in vitro."} {"id": "PMID:169612", "title": "[Ultrastructure of the cytoplasm of the lower holotrichous infusorian Tracheloraphis prenanti].", "content": "The ciliature of T. prenanti Dragesco 1960 (forma oligocineta Raikov et Kovaleva, 1968) consists of 14-18 ventral and lateral longitudinal kineties with paired kinetosomes, carrying either two cilia or one cilium per kinetosome pair (in the latter case, the nonciliated kinetosome is always the posterior one). The ectoplasmic fibrillar system belongs to the postciliary type. A pair of kinetosomes shares a common basal plate. The anterior kinetosome gives rise to a short ribbon of transverse microtubules, the posterior one, to a poorly developed kinetodesmal filament and to a strong ribbon of postciliary microtubules. The latter proceeds backwards along 8 to 12 kinetosome pairs, being incorporated into a laminated postciliodesma which accompanies each kinety on its right side. Rows of Golgi elements, sending secretory vesicles and channels towards the body surface, exist beneath the kinetosome bases. Each kinety is accompanied on its left by a microfibrillar myoneme, surrounded by perimyary vesicles and underlain by a row of mitochondria. The median part of the dorsal surface is nonciliated; the cytoplasm here is rich of membrane systems, contains peripheral, electron-dense, extrusible inclusions and sometimes also bacteria. The electron-dense inclusions develop in the endoplasm, in close contact with mitochondria. The endoplasm contains also large microfibrillar spheres of unknown nature.", "contents": "[Ultrastructure of the cytoplasm of the lower holotrichous infusorian Tracheloraphis prenanti]. The ciliature of T. prenanti Dragesco 1960 (forma oligocineta Raikov et Kovaleva, 1968) consists of 14-18 ventral and lateral longitudinal kineties with paired kinetosomes, carrying either two cilia or one cilium per kinetosome pair (in the latter case, the nonciliated kinetosome is always the posterior one). The ectoplasmic fibrillar system belongs to the postciliary type. A pair of kinetosomes shares a common basal plate. The anterior kinetosome gives rise to a short ribbon of transverse microtubules, the posterior one, to a poorly developed kinetodesmal filament and to a strong ribbon of postciliary microtubules. The latter proceeds backwards along 8 to 12 kinetosome pairs, being incorporated into a laminated postciliodesma which accompanies each kinety on its right side. Rows of Golgi elements, sending secretory vesicles and channels towards the body surface, exist beneath the kinetosome bases. Each kinety is accompanied on its left by a microfibrillar myoneme, surrounded by perimyary vesicles and underlain by a row of mitochondria. The median part of the dorsal surface is nonciliated; the cytoplasm here is rich of membrane systems, contains peripheral, electron-dense, extrusible inclusions and sometimes also bacteria. The electron-dense inclusions develop in the endoplasm, in close contact with mitochondria. The endoplasm contains also large microfibrillar spheres of unknown nature."} {"id": "PMID:169613", "title": "[Electron microscopic study of intracellular digestion in intestinal cells of the ixodid tick Hyalomma asiaticum. I. Formation of primary and secondary lysosomes].", "content": "The formation of primary and secondary lysosomes in digestive cells of midgut of the tick H. asiaticum was investigated using ultracytochemical methods for acid phosphatase. This enzyme is synthesized in the rough endoplasmic reticulum cisternae to be concentrated in the Golgi complex. Vesicles 0.1-0.15 mum in diameter filled with the enzyme are propagated from the distal Golgi cisternae which are primary lysosomes. Secondary lysosomes are produced in result of fusion of primary lysosomes with heterophagosomes that appear during endocytosis. Another type of structures responsible for transport of lysosomal enzymes into heterophagosomes is represented by dense bodies 0.3-0.5 mum in size. These are rich in acid phosphatase being different stages of heterophagolysosomes and telolysosomes.", "contents": "[Electron microscopic study of intracellular digestion in intestinal cells of the ixodid tick Hyalomma asiaticum. I. Formation of primary and secondary lysosomes]. The formation of primary and secondary lysosomes in digestive cells of midgut of the tick H. asiaticum was investigated using ultracytochemical methods for acid phosphatase. This enzyme is synthesized in the rough endoplasmic reticulum cisternae to be concentrated in the Golgi complex. Vesicles 0.1-0.15 mum in diameter filled with the enzyme are propagated from the distal Golgi cisternae which are primary lysosomes. Secondary lysosomes are produced in result of fusion of primary lysosomes with heterophagosomes that appear during endocytosis. Another type of structures responsible for transport of lysosomal enzymes into heterophagosomes is represented by dense bodies 0.3-0.5 mum in size. These are rich in acid phosphatase being different stages of heterophagolysosomes and telolysosomes."} {"id": "PMID:169614", "title": "[Morphological and cytochemical characteristics of human cells transformed and made malignant by Rous and polyoma viruses].", "content": "In cells of human embryo skin--muscle tissue transformed by the Rouse sarcoma virus (23rd cell line) and polyoma virus (P-2 cell line), the mitotic activity was 48 0/00 for 23rd line, 51 0/00 for P-2 line as against 28 0/00 in the control cells. The transformed cells possessed greater amounts of RNA and DNA and protein--bound SH-groups, different forms of glycogen deposits, as well as higher acid phosphatase enzyme activities; there was practically no difference in acid mucopolysaccharide content or NAD-H2-diaphorase and succinate dehydrogenase activities.", "contents": "[Morphological and cytochemical characteristics of human cells transformed and made malignant by Rous and polyoma viruses]. In cells of human embryo skin--muscle tissue transformed by the Rouse sarcoma virus (23rd cell line) and polyoma virus (P-2 cell line), the mitotic activity was 48 0/00 for 23rd line, 51 0/00 for P-2 line as against 28 0/00 in the control cells. The transformed cells possessed greater amounts of RNA and DNA and protein--bound SH-groups, different forms of glycogen deposits, as well as higher acid phosphatase enzyme activities; there was practically no difference in acid mucopolysaccharide content or NAD-H2-diaphorase and succinate dehydrogenase activities."} {"id": "PMID:169615", "title": "[Bovine enzootic leukemia and study of c-type particles in a cow with acute lymphatic leukemia and in cattle of the same herd with persistent lymphocytosis].", "content": "A case of acute lymphatic leukemia in a 7-month-pregnant Italian Friesian cow, aged about 6 years and belonging to a small dairy herd of 11 cows is described. Hematologic, histopatologic and ultrastructural examinations were performed, the ultrastructural studies were confined to the lymphnodes, thymus and buffy-coat cultures from peripheral blood. The remaining animals were subjected to hematologic examination and electron microscopy examination of buffy-coat cultures from peripheral blood. C-type particles were found in phytohemagglutinin (PHA)-treated and untreated buffy-coat cultures from the leukemic cow and from the animals with persistent lymphocytosis. C-type particles were also found in milk samples from 3 cows with persistent lymphocytosis.", "contents": "[Bovine enzootic leukemia and study of c-type particles in a cow with acute lymphatic leukemia and in cattle of the same herd with persistent lymphocytosis]. A case of acute lymphatic leukemia in a 7-month-pregnant Italian Friesian cow, aged about 6 years and belonging to a small dairy herd of 11 cows is described. Hematologic, histopatologic and ultrastructural examinations were performed, the ultrastructural studies were confined to the lymphnodes, thymus and buffy-coat cultures from peripheral blood. The remaining animals were subjected to hematologic examination and electron microscopy examination of buffy-coat cultures from peripheral blood. C-type particles were found in phytohemagglutinin (PHA)-treated and untreated buffy-coat cultures from the leukemic cow and from the animals with persistent lymphocytosis. C-type particles were also found in milk samples from 3 cows with persistent lymphocytosis."} {"id": "PMID:169616", "title": "[Multivariate analysis of aminoacyl-tRNA synthetase activities of liver and hepatomas (author's transl)].", "content": "Data on the aminoacyl-tRNA synthetase activities in normal liver and in three transplantable rat hepatomas, viz Yoshida's AH 130 and Morris's 5123C and 7793, were studied by means of factor analysis, a powerful technique of multivariate analysis particularly suitable foridentifying factors which theoretically may account for the pattern of interrelations between several variables. The analysis has been performed on 51 patterns of enzyme activities, covering 17 out of the 20 aminoacyl-tRNA synthetases; 80% on average of the total variability of the 17 enzyme activities may be accounted for by the first 4 factors extracted. The enzymes seem to fall into different groups, depending on their relationship with the factors thus identified. The results suggest that enzymes belonging to the same group share a common control mechanism, and are independent of the enzymes belonging to different groups, both in normal liver and in hepatomas.", "contents": "[Multivariate analysis of aminoacyl-tRNA synthetase activities of liver and hepatomas (author's transl)]. Data on the aminoacyl-tRNA synthetase activities in normal liver and in three transplantable rat hepatomas, viz Yoshida's AH 130 and Morris's 5123C and 7793, were studied by means of factor analysis, a powerful technique of multivariate analysis particularly suitable foridentifying factors which theoretically may account for the pattern of interrelations between several variables. The analysis has been performed on 51 patterns of enzyme activities, covering 17 out of the 20 aminoacyl-tRNA synthetases; 80% on average of the total variability of the 17 enzyme activities may be accounted for by the first 4 factors extracted. The enzymes seem to fall into different groups, depending on their relationship with the factors thus identified. The results suggest that enzymes belonging to the same group share a common control mechanism, and are independent of the enzymes belonging to different groups, both in normal liver and in hepatomas."} {"id": "PMID:169622", "title": "[The ultrastructure of mixed mammary gland tumours in bitches. III. The early stages of the myoepithelial proliferation (author's transl)].", "content": "The early stages of myoepithelial proliferation in 14 mixed canine mammary tumours were studied by light- and electron microscopy. Two different early stages can be distinguished: 1. Proliferations inside the basal lamina with partial maintenance of the organoid pattern. 2. Proliferations with a break through the basal lamina and transposition of tumour cells into the surrounding connective tissue. The intracytoplasmic fibrillae of myoepithelial tumour cells are striped periodically and thicker than those of normal myothelia. It is suggested that the amorphous as well as the fibrous intercellular substance in the early stages is derived from the described myoepithelial tumour cells.", "contents": "[The ultrastructure of mixed mammary gland tumours in bitches. III. The early stages of the myoepithelial proliferation (author's transl)]. The early stages of myoepithelial proliferation in 14 mixed canine mammary tumours were studied by light- and electron microscopy. Two different early stages can be distinguished: 1. Proliferations inside the basal lamina with partial maintenance of the organoid pattern. 2. Proliferations with a break through the basal lamina and transposition of tumour cells into the surrounding connective tissue. The intracytoplasmic fibrillae of myoepithelial tumour cells are striped periodically and thicker than those of normal myothelia. It is suggested that the amorphous as well as the fibrous intercellular substance in the early stages is derived from the described myoepithelial tumour cells."} {"id": "PMID:169628", "title": "[Use of cross-absorbed sera in neutralization tests with viral titration by the cytopathogenic effect].", "content": "A new method for intratypic antigenic differentiation of poliovirus strains has been developed. The method is based on the use of cross-absorbed sera in neutralization tests where virus is titrated by the cytopathic effect. Qualitative differences between the antigenic structure of vaccine and \"wild\" strains as well as between some \"wild\" strains of the same serologic type have been found. The method may be used in practical laboratories.", "contents": "[Use of cross-absorbed sera in neutralization tests with viral titration by the cytopathogenic effect]. A new method for intratypic antigenic differentiation of poliovirus strains has been developed. The method is based on the use of cross-absorbed sera in neutralization tests where virus is titrated by the cytopathic effect. Qualitative differences between the antigenic structure of vaccine and \"wild\" strains as well as between some \"wild\" strains of the same serologic type have been found. The method may be used in practical laboratories."} {"id": "PMID:169629", "title": "[Results of examining wild monkeys for the presence of smallpox antibodies and smallpox group viruses].", "content": "The results of examinations of sera, blood and organs of different species of monkeys from some Asian and African countries for the presence of antibody to smallpox and viruses of the smallpox group. Significant titers of smallpox antibodies (antihemagglutinins virus-neutralizing and, in some cases, precipitating antibody) were found in a considerable number of monkeys shot near foci with human cases (Equatorial province of Zair Republic). In the same monkeys kidney tissues yielded 3 isolates of smallpox virus group two of which were indistinguishable in the laboratory tests from variola virus. On the basis of these data it is concluded that smallpox viruses circulate among wildlife monkeys in some areas of Equatorial Africa. Further studies along these lines are necessary.", "contents": "[Results of examining wild monkeys for the presence of smallpox antibodies and smallpox group viruses]. The results of examinations of sera, blood and organs of different species of monkeys from some Asian and African countries for the presence of antibody to smallpox and viruses of the smallpox group. Significant titers of smallpox antibodies (antihemagglutinins virus-neutralizing and, in some cases, precipitating antibody) were found in a considerable number of monkeys shot near foci with human cases (Equatorial province of Zair Republic). In the same monkeys kidney tissues yielded 3 isolates of smallpox virus group two of which were indistinguishable in the laboratory tests from variola virus. On the basis of these data it is concluded that smallpox viruses circulate among wildlife monkeys in some areas of Equatorial Africa. Further studies along these lines are necessary."} {"id": "PMID:169634", "title": "Ocular complications in renal transplant recipients.", "content": "Twenty-five patients were examined for ocular complaints following renal transplantation. Besides the expected complications of posterior subcapsular cataract and cytomegalovirus retinitis, other findings-such as focal depigmentation of the retinal pigment epithelium, a lack of hypertensive retinopathy, elevated intraocular tensions, microaneurysms, preretinal wrinkling, serous detachments of the retina, hemorrhages and exudates-were observed.A laboratory clue to the onset of cytomegalovirus retinitis was a rapid rise in cytomegalovirus (CMV) antibody titer and a positive CMV plaque count in tissue culture.", "contents": "Ocular complications in renal transplant recipients. Twenty-five patients were examined for ocular complaints following renal transplantation. Besides the expected complications of posterior subcapsular cataract and cytomegalovirus retinitis, other findings-such as focal depigmentation of the retinal pigment epithelium, a lack of hypertensive retinopathy, elevated intraocular tensions, microaneurysms, preretinal wrinkling, serous detachments of the retina, hemorrhages and exudates-were observed.A laboratory clue to the onset of cytomegalovirus retinitis was a rapid rise in cytomegalovirus (CMV) antibody titer and a positive CMV plaque count in tissue culture."} {"id": "PMID:169631", "title": "[Morphological manifestations of the intracellular toxic effect of microorganisms of the ornithosis-lymphogranuloma-trachoma group].", "content": "Interactions of the causative agents of meningopneumonia and ovine abortion with pulmonary macrophages in experimental infection in white mice were studied by histological, immunofluorescent and electron microscopic methods. The causative agent of meningopneumonia did not multiply in colonies and caused toxic lesions in the cells and formed cytoplasmic oxiphilic inclusion bodies. Being the product of cell degeneration, these oxiphilic inclusion bodies were conducive to long-term survival of the cell and slow release from them of elementary bodies of meningopneumonia agent. The agent of ovine abortion multiplied in colonies without toxic affection of the cells or formation of oxiphilic inclusion bodies. It is suggested that oxiphilic inclusion bodies represent morphological manifestation of the intracellular toxic effect of rickettsial and ornithosis-like agents possessing dissociated (non-colonial) mode of multiplication.", "contents": "[Morphological manifestations of the intracellular toxic effect of microorganisms of the ornithosis-lymphogranuloma-trachoma group]. Interactions of the causative agents of meningopneumonia and ovine abortion with pulmonary macrophages in experimental infection in white mice were studied by histological, immunofluorescent and electron microscopic methods. The causative agent of meningopneumonia did not multiply in colonies and caused toxic lesions in the cells and formed cytoplasmic oxiphilic inclusion bodies. Being the product of cell degeneration, these oxiphilic inclusion bodies were conducive to long-term survival of the cell and slow release from them of elementary bodies of meningopneumonia agent. The agent of ovine abortion multiplied in colonies without toxic affection of the cells or formation of oxiphilic inclusion bodies. It is suggested that oxiphilic inclusion bodies represent morphological manifestation of the intracellular toxic effect of rickettsial and ornithosis-like agents possessing dissociated (non-colonial) mode of multiplication."} {"id": "PMID:169630", "title": "[Damaging effect of 2 simian viruses on mammalian cell chromosomes].", "content": "A green monkey myxovirus (SV5) causes chromosome breaks in embryonal diploid fibroblasts of man, cotton rats, striped hairy-footed hamster, and in cells of one heteroploid line of newborn lamb kidney. Adenovirus SV15 is mutagenic for all cultures under study (diploid strains of human and cotton rat embryo fibroblasts and three continuous kidney cell lines from newborn lambs). The mutagenic activity of these viruses may be manifested without their undergoing a complete cycle of replication.", "contents": "[Damaging effect of 2 simian viruses on mammalian cell chromosomes]. A green monkey myxovirus (SV5) causes chromosome breaks in embryonal diploid fibroblasts of man, cotton rats, striped hairy-footed hamster, and in cells of one heteroploid line of newborn lamb kidney. Adenovirus SV15 is mutagenic for all cultures under study (diploid strains of human and cotton rat embryo fibroblasts and three continuous kidney cell lines from newborn lambs). The mutagenic activity of these viruses may be manifested without their undergoing a complete cycle of replication."} {"id": "PMID:169633", "title": "[Characteristics of experimental para-influenza in Syrian hamsters infected by different routes].", "content": "The pathomorphological and virological study of peculiar features of parainfluenza infection caused by intranasal, aerosol and oral administration of the virus was carried out. The most marked lesions in the respiratory tract were observed in hamsters infected by the intranasal route, whereas with other routes of infection the intensity of lesions was minimal. Such differences in the pathomorphological manifestations of the process are most probably due to uneven distribution of the virus in the respiratory organs and to peculiar features of the immunological response of the animals.", "contents": "[Characteristics of experimental para-influenza in Syrian hamsters infected by different routes]. The pathomorphological and virological study of peculiar features of parainfluenza infection caused by intranasal, aerosol and oral administration of the virus was carried out. The most marked lesions in the respiratory tract were observed in hamsters infected by the intranasal route, whereas with other routes of infection the intensity of lesions was minimal. Such differences in the pathomorphological manifestations of the process are most probably due to uneven distribution of the virus in the respiratory organs and to peculiar features of the immunological response of the animals."} {"id": "PMID:169640", "title": "Serologic studies of acute respiratory infections in military personnel.", "content": "The advantages, disadvantages, and uses of serological epidemiology are discussed in relation to acute respiratory infections in military personnel. The prevalence of antibody reflects both current and past experience with respiratory agents and is a measure of susceptinility. Incidence data calculated by testing two serial serum samples, on entry and discharge from the service, has indicated high influenza and mycoplasma pneumoniae rates in South American recruits and low rates of adenovirus and parainfluenza infections. Serologic analysis of reinfection rates showed high protection against influenza infections at HI antibody levels of over 1:40, against adenovirus infections at neutralizing titers of 1:5, and against M. pneumoniae infections at TRI antibody levels over 1:8. Antibody responses persisting at least 7 mo following immunization were demonstrated in 70% of 428 vaccinated young adults for A2 antigen and 20% for influenza B antigen. No relation of ABO blood groups to respiratory infection was found. The lack of myxovirus infections in four Polaris submarines is presented.", "contents": "Serologic studies of acute respiratory infections in military personnel. The advantages, disadvantages, and uses of serological epidemiology are discussed in relation to acute respiratory infections in military personnel. The prevalence of antibody reflects both current and past experience with respiratory agents and is a measure of susceptinility. Incidence data calculated by testing two serial serum samples, on entry and discharge from the service, has indicated high influenza and mycoplasma pneumoniae rates in South American recruits and low rates of adenovirus and parainfluenza infections. Serologic analysis of reinfection rates showed high protection against influenza infections at HI antibody levels of over 1:40, against adenovirus infections at neutralizing titers of 1:5, and against M. pneumoniae infections at TRI antibody levels over 1:8. Antibody responses persisting at least 7 mo following immunization were demonstrated in 70% of 428 vaccinated young adults for A2 antigen and 20% for influenza B antigen. No relation of ABO blood groups to respiratory infection was found. The lack of myxovirus infections in four Polaris submarines is presented."} {"id": "PMID:169641", "title": "[Dermatoglyphics in children with embryonic tumors (author's transl)].", "content": "Dermatoglyphics were analyzed in 60 children with embryonic tumors. In comparison with normal children, several differences were found. Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained. These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details.", "contents": "[Dermatoglyphics in children with embryonic tumors (author's transl)]. Dermatoglyphics were analyzed in 60 children with embryonic tumors. In comparison with normal children, several differences were found. Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained. These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details."} {"id": "PMID:169642", "title": "Electron microscopic and electron histochemical studies on embryonal rhabdomyosarcoma of the orbit.", "content": "A small number of differentiated tumor cells could be found besides a great number of undifferentiated ones. Abnormal dense granules were found in the nuclei of undifferentiated tumor cells, not in differentiated ones. Non-specific filaments were seen in the cytoplasm of undifferentiated tumor cells. Differentiated tumor cells demonstrated various stages of myofibrillar structures such as A, I, and Z bands, many glycogen granules, mitochondria and a basement membrane. Polyglucose particles synthesized from glycose-1-phosphate by phosphorylase activity were located in the cytoplasmic matrix of undifferentiated and differentiated tumor cells and in the karyolymph of undifferentiated tumor cells. Polyglucose partices increased in number according to the degree of differentiation of tumor cells.", "contents": "Electron microscopic and electron histochemical studies on embryonal rhabdomyosarcoma of the orbit. A small number of differentiated tumor cells could be found besides a great number of undifferentiated ones. Abnormal dense granules were found in the nuclei of undifferentiated tumor cells, not in differentiated ones. Non-specific filaments were seen in the cytoplasm of undifferentiated tumor cells. Differentiated tumor cells demonstrated various stages of myofibrillar structures such as A, I, and Z bands, many glycogen granules, mitochondria and a basement membrane. Polyglucose particles synthesized from glycose-1-phosphate by phosphorylase activity were located in the cytoplasmic matrix of undifferentiated and differentiated tumor cells and in the karyolymph of undifferentiated tumor cells. Polyglucose partices increased in number according to the degree of differentiation of tumor cells."} {"id": "PMID:169643", "title": "The use of fluorescent probes for studying the interaction of proteins with black lipid membranes.", "content": "The number of 1-anilino-8-naphthalene sulphonate (ANS) molecules bound to black phosphatidylcholine (PC) and phosphatidylinositol (PI)-membranes was calculated. The fluorescences change of membrane bound ANS was measured after the additon of positively charged proteins to the same side as ANS. Cytochrome c caused a fluorescence decrease, lysozyme and protamine an increase. These effects were completely reversible in the case of cytochrome c and lysozyme and only partly reversible in the case of protamine by increasing the ionic strength. The fluorescence polarization of membrane bound ANS was not significantly changed by protein addition. The results are discussed with respect to the binding of proteins to black lipid membranes and the use of ANS as a probe compared with other fluorescent probes.", "contents": "The use of fluorescent probes for studying the interaction of proteins with black lipid membranes. The number of 1-anilino-8-naphthalene sulphonate (ANS) molecules bound to black phosphatidylcholine (PC) and phosphatidylinositol (PI)-membranes was calculated. The fluorescences change of membrane bound ANS was measured after the additon of positively charged proteins to the same side as ANS. Cytochrome c caused a fluorescence decrease, lysozyme and protamine an increase. These effects were completely reversible in the case of cytochrome c and lysozyme and only partly reversible in the case of protamine by increasing the ionic strength. The fluorescence polarization of membrane bound ANS was not significantly changed by protein addition. The results are discussed with respect to the binding of proteins to black lipid membranes and the use of ANS as a probe compared with other fluorescent probes."} {"id": "PMID:169649", "title": "Ultrastructure of acinar cells of submaxillary gland after treatment with ACTH and cortisone.", "content": "The applied hormones cause changes in the ultrastructure of acinar cells, and the changes caused by each of them are different. The effect of ACTH on these cells is more distinct and the nature of the changes permits the suggestion that ACTH acts mainly on secretory activity (increase). The changes caused by treatment with cortisone cannot be interpreted unequivocally.", "contents": "Ultrastructure of acinar cells of submaxillary gland after treatment with ACTH and cortisone. The applied hormones cause changes in the ultrastructure of acinar cells, and the changes caused by each of them are different. The effect of ACTH on these cells is more distinct and the nature of the changes permits the suggestion that ACTH acts mainly on secretory activity (increase). The changes caused by treatment with cortisone cannot be interpreted unequivocally."} {"id": "PMID:169651", "title": "[Studies on the influence of the host system on the result of the neutralization of monodispersed and untreated foot- and mouth disease virus (author's transl)].", "content": "Monodispersed foot- and mouth disease virus was obtained by filtration through membranes having a porosity only twice the diameter of the virus. This monodispersed virus was neutralized by immune sera in the same manner as not treated virus. This was shown by the inactivation curve comparing the amount of virus used for the test (calculated as ID50) with the neutralization titre (ND50) or comparing the reduction of infectivity (also calculated as ID50) with the dilution factor of the antiserum. When the virus was assayed by counting the plaque forming units, the monodispersed virus needed more antiserum to be neutralized than a not treated virus suspension. The same mixtures of virus and antiserum were inoculated into different host systems. Using suckling mice there was observed only about 1% of the infectivity measured in primary calf kidney cells. Primary calf kidney cells showed only a tenth of the infectivity seen in BHK-21 cells. The difference between the results in mice and calf kidney cells has been found to be caused by the existence of infectious virus in the mice, which does not cause illness or death in the presence of antibodies. Comparing the same size of cell sheet there is more virus absorbed by BHK-cells in the presence of antibodies than by calf kidney cells. The different results obtained in different hosts for the same virus antibody mixtures are discussed with respect to the detection of small amounts of antibodies and to the limits for the comparison of neutralization titres.", "contents": "[Studies on the influence of the host system on the result of the neutralization of monodispersed and untreated foot- and mouth disease virus (author's transl)]. Monodispersed foot- and mouth disease virus was obtained by filtration through membranes having a porosity only twice the diameter of the virus. This monodispersed virus was neutralized by immune sera in the same manner as not treated virus. This was shown by the inactivation curve comparing the amount of virus used for the test (calculated as ID50) with the neutralization titre (ND50) or comparing the reduction of infectivity (also calculated as ID50) with the dilution factor of the antiserum. When the virus was assayed by counting the plaque forming units, the monodispersed virus needed more antiserum to be neutralized than a not treated virus suspension. The same mixtures of virus and antiserum were inoculated into different host systems. Using suckling mice there was observed only about 1% of the infectivity measured in primary calf kidney cells. Primary calf kidney cells showed only a tenth of the infectivity seen in BHK-21 cells. The difference between the results in mice and calf kidney cells has been found to be caused by the existence of infectious virus in the mice, which does not cause illness or death in the presence of antibodies. Comparing the same size of cell sheet there is more virus absorbed by BHK-cells in the presence of antibodies than by calf kidney cells. The different results obtained in different hosts for the same virus antibody mixtures are discussed with respect to the detection of small amounts of antibodies and to the limits for the comparison of neutralization titres."} {"id": "PMID:169652", "title": "Influence of Bordetella pertussis and bacterial endotoxins on the immunological reactivity of germfree mice.", "content": "As compared to specifically pathogen-free NMRI mice, in principle, the immunological reactivity of germfree mice of the same strain and age was not found to be reduced. This is documented by the cellular kinetics of the primary immune responses, evoked by the intraperitoneal (i.p.) injection of either a \"saturated\" dose of 4 times 10(8) sheep erythrocytes (SE) or the simultaneous injection of 4 times 10(8) SE and 3 times 10(9) killed Bordetella pertussis organisms (PO). Thereby, adjuvancy of PO was not found to be reduced in germfree mice. The only difference consisted in the demonstration of significantly reduced numbers of both direct and indirect plaque-forming spleen cells (PFC) on the 4th day after primary antigenic stimulation. This is suggested to be due to a lack of sufficient training of the immunological apparatus of germfree mice. Both in germfree and conventional mice significant splenomegaly, blood leukocytosis as well as increase in the numbers of pre-existing \"background\" PFC became detectable following a single i.p. injection of 3 times 10(9) PO without SE. Similarly, the injection of endotoxin from Serratia marcescens produced a moderate increase in the numbers of \"background\" PFC. From the data presented it is suggested that strict gnotobiotic conditions do not cause noteworthy deficiency in immunological competence.", "contents": "Influence of Bordetella pertussis and bacterial endotoxins on the immunological reactivity of germfree mice. As compared to specifically pathogen-free NMRI mice, in principle, the immunological reactivity of germfree mice of the same strain and age was not found to be reduced. This is documented by the cellular kinetics of the primary immune responses, evoked by the intraperitoneal (i.p.) injection of either a \"saturated\" dose of 4 times 10(8) sheep erythrocytes (SE) or the simultaneous injection of 4 times 10(8) SE and 3 times 10(9) killed Bordetella pertussis organisms (PO). Thereby, adjuvancy of PO was not found to be reduced in germfree mice. The only difference consisted in the demonstration of significantly reduced numbers of both direct and indirect plaque-forming spleen cells (PFC) on the 4th day after primary antigenic stimulation. This is suggested to be due to a lack of sufficient training of the immunological apparatus of germfree mice. Both in germfree and conventional mice significant splenomegaly, blood leukocytosis as well as increase in the numbers of pre-existing \"background\" PFC became detectable following a single i.p. injection of 3 times 10(9) PO without SE. Similarly, the injection of endotoxin from Serratia marcescens produced a moderate increase in the numbers of \"background\" PFC. From the data presented it is suggested that strict gnotobiotic conditions do not cause noteworthy deficiency in immunological competence."} {"id": "PMID:169657", "title": "The significance of serum progesterone and serum unconjugated oestradiol-17beta in unaborted hydatidiform mole.", "content": "Both serum progesterone and serum unconjugated oestradiol-17beta (Oe2) were measured by competitive protein binding assay and radioimmunoassay respectively in 42 cases of unaborted hydatidiform mole. Serum human chorionic gonadotrophin (HCG) was measured by a haemagglutination-inhibition technique. In 26 cases of intact molar pregnancies without theca lutein cysts (TLC), serum progesterone ranged from 18.0 to 289.0 ng/ml with a mean +/- standard error of the mean (SEM) of 65.9 +/- 13.1 ng/ml; serum Oe2 ranged from 4.0 to 37.0 ng/ml with a mean +/- SEM of 17.9 +/- 1.9 ng/ml; serum HCG ranged from 60 to 1920 IU/ml with a mean +/- SEM of 531.5 +/- 105.7 IU/ml. In contrast, 16 cases of intact molar pregnancies with TLC had serum progesterone ranging from 34.1 to 288.0 ng/ml with a mean +/- SEM of 134.1 +/- 2.4 ng/ml; serum Oe2 ranging from 1.7 to 76.3 ng/ml with a mean +/- SEM of 31.5 +/- 5.3 ng/ml; serum HCG ranging from 320 to 2560 IU/ml with a mean +/- SEM 1400 +/- 196.2 ng/ml. The differences between the mean of these three hormones in hydatidiform mole with and without TLC were significant (progesterone: P less than 0.005; Oe2: P less than 0,0125; HCG: P less than 0.005). There was a significant correlation between serum HCG and serum Oe2 (coefficient of correlation r = +0.3565, P less than 0.0125) and between serum Oe2 and serum progesterone (r = +0.3787, P less than 0.0125). There was no significant difference in the mean levels of serum progesterone, Oe2 and HCG in hydatidiform mole with and without subsequent malignant sequelae. The mean ratios of Oe2/progesterone were essentially similar in moles with and without TLC and with and without malignant sequelae. The significance of these findings are discussed.", "contents": "The significance of serum progesterone and serum unconjugated oestradiol-17beta in unaborted hydatidiform mole. Both serum progesterone and serum unconjugated oestradiol-17beta (Oe2) were measured by competitive protein binding assay and radioimmunoassay respectively in 42 cases of unaborted hydatidiform mole. Serum human chorionic gonadotrophin (HCG) was measured by a haemagglutination-inhibition technique. In 26 cases of intact molar pregnancies without theca lutein cysts (TLC), serum progesterone ranged from 18.0 to 289.0 ng/ml with a mean +/- standard error of the mean (SEM) of 65.9 +/- 13.1 ng/ml; serum Oe2 ranged from 4.0 to 37.0 ng/ml with a mean +/- SEM of 17.9 +/- 1.9 ng/ml; serum HCG ranged from 60 to 1920 IU/ml with a mean +/- SEM of 531.5 +/- 105.7 IU/ml. In contrast, 16 cases of intact molar pregnancies with TLC had serum progesterone ranging from 34.1 to 288.0 ng/ml with a mean +/- SEM of 134.1 +/- 2.4 ng/ml; serum Oe2 ranging from 1.7 to 76.3 ng/ml with a mean +/- SEM of 31.5 +/- 5.3 ng/ml; serum HCG ranging from 320 to 2560 IU/ml with a mean +/- SEM 1400 +/- 196.2 ng/ml. The differences between the mean of these three hormones in hydatidiform mole with and without TLC were significant (progesterone: P less than 0.005; Oe2: P less than 0,0125; HCG: P less than 0.005). There was a significant correlation between serum HCG and serum Oe2 (coefficient of correlation r = +0.3565, P less than 0.0125) and between serum Oe2 and serum progesterone (r = +0.3787, P less than 0.0125). There was no significant difference in the mean levels of serum progesterone, Oe2 and HCG in hydatidiform mole with and without subsequent malignant sequelae. The mean ratios of Oe2/progesterone were essentially similar in moles with and without TLC and with and without malignant sequelae. The significance of these findings are discussed."} {"id": "PMID:169659", "title": "Pentose shunt, phosphoribosylpyrophosphate generation and purine-phosphoribosyltransferases in erythrocytes of patients with polycythemia vera.", "content": "Erythrocytes of patients with polycythemia vera exhibited increased activity of oxidative pentose shunt, accelerated generation of phosphoribosylpyrophosphate, increased incorporation of 14C-adenine into nucleotides, and increased activity and thermostability of adenine-phosphoribosyltransferase. These abnormalities are attributed to age dependency of the pathways concerned and presence in polycythemia vera of an erythrocyte population younger than normal.", "contents": "Pentose shunt, phosphoribosylpyrophosphate generation and purine-phosphoribosyltransferases in erythrocytes of patients with polycythemia vera. Erythrocytes of patients with polycythemia vera exhibited increased activity of oxidative pentose shunt, accelerated generation of phosphoribosylpyrophosphate, increased incorporation of 14C-adenine into nucleotides, and increased activity and thermostability of adenine-phosphoribosyltransferase. These abnormalities are attributed to age dependency of the pathways concerned and presence in polycythemia vera of an erythrocyte population younger than normal."} {"id": "PMID:169660", "title": "Parallel tubular structures in lymphocytes. II. Correlation with cellular immunity and cytomegalovirus and Epstein-Barr virus antibodies in Hodgkin's disease.", "content": "The increased incidence of parallel tubular structures in lymphocytes of patients with Hodgkin's disease was investigated for a correlation with either impairment of cellular immunity (measured by DNCB-skin test and PHA-induced lymphocyte stimulation in vitro) or an increase of antibodies against cytomegalovirus or Epstein-Barr virus. No correlations were found. Statistical analysis revealed antibody titers especially in the group of patients with high percentages of lymphocytes containing the tubular inclusions. This probably reflects only the connection between these findings and the progression of the disease. The nature and function of the parallel tubular structures have to be investigated further. In Hodgkin's disease they may have significance for the understanding of an alteration in lymphocyte function and morphology.", "contents": "Parallel tubular structures in lymphocytes. II. Correlation with cellular immunity and cytomegalovirus and Epstein-Barr virus antibodies in Hodgkin's disease. The increased incidence of parallel tubular structures in lymphocytes of patients with Hodgkin's disease was investigated for a correlation with either impairment of cellular immunity (measured by DNCB-skin test and PHA-induced lymphocyte stimulation in vitro) or an increase of antibodies against cytomegalovirus or Epstein-Barr virus. No correlations were found. Statistical analysis revealed antibody titers especially in the group of patients with high percentages of lymphocytes containing the tubular inclusions. This probably reflects only the connection between these findings and the progression of the disease. The nature and function of the parallel tubular structures have to be investigated further. In Hodgkin's disease they may have significance for the understanding of an alteration in lymphocyte function and morphology."} {"id": "PMID:169662", "title": "Cyclic changes in the uterine phosphatases of Suncus murinus sindensis Anderson, the Indian common house shrew.", "content": "Cyclic changes in the phosphatases were studied histochemically in the uterine complex of the female Suncus. Alkaline phosphatase activity showed constant and predictable changes in the various phases of the cycle with the maximum activity during metaestrus. Acid phosphatase and ATPase activities also showed constant changes with moderate activity during diestrus and proestrus but with maximal activities during estrus and metaestrus. No proper localization of the enzyme is discernible in the case of G-1-Pase and G-6-Pase.", "contents": "Cyclic changes in the uterine phosphatases of Suncus murinus sindensis Anderson, the Indian common house shrew. Cyclic changes in the phosphatases were studied histochemically in the uterine complex of the female Suncus. Alkaline phosphatase activity showed constant and predictable changes in the various phases of the cycle with the maximum activity during metaestrus. Acid phosphatase and ATPase activities also showed constant changes with moderate activity during diestrus and proestrus but with maximal activities during estrus and metaestrus. No proper localization of the enzyme is discernible in the case of G-1-Pase and G-6-Pase."} {"id": "PMID:169663", "title": "Histochemical localization of enzyme activity in the kidneys of male marmosets (Callithrix jacchus and Callithrix penicillata).", "content": "The distribution of several hydrolases and oxidoreductases was studied in the renal parenchyma of adult male marmosets (Callithrix jacchus and Callithrix penicillata). The oxidative enzymes showed a high reactivity in the proximal and distal tubules, whereas the hydrolases reacted strongly in the proximal tubules but only weakly or not at all in the thick limb of Henle's loop, distal tubules and collecting ducts. The NAD-dependent enzymes (except alpha-GPDH) showed a stronger reactivity in the proximal tubules, while the NADP-dependent ones were more reactive in the thick limb of Henle's loop and distal convoluted tubules. Two groups of interstitial cells were found in the medulla. A first group inside the outer medulla, showing cells rich in acid phosphatase and nonspecific esterases and a second group, close to the papilla, reactive to a certain number of oxidative enzymes. A different reactivity in cells of the distal convoluted tubules, thick limb of Henle's loops and collecting ducts (dark cells) was seen in the case of some enzymes like nonspecific esterase, alpha-GPDH and SDH.", "contents": "Histochemical localization of enzyme activity in the kidneys of male marmosets (Callithrix jacchus and Callithrix penicillata). The distribution of several hydrolases and oxidoreductases was studied in the renal parenchyma of adult male marmosets (Callithrix jacchus and Callithrix penicillata). The oxidative enzymes showed a high reactivity in the proximal and distal tubules, whereas the hydrolases reacted strongly in the proximal tubules but only weakly or not at all in the thick limb of Henle's loop, distal tubules and collecting ducts. The NAD-dependent enzymes (except alpha-GPDH) showed a stronger reactivity in the proximal tubules, while the NADP-dependent ones were more reactive in the thick limb of Henle's loop and distal convoluted tubules. Two groups of interstitial cells were found in the medulla. A first group inside the outer medulla, showing cells rich in acid phosphatase and nonspecific esterases and a second group, close to the papilla, reactive to a certain number of oxidative enzymes. A different reactivity in cells of the distal convoluted tubules, thick limb of Henle's loops and collecting ducts (dark cells) was seen in the case of some enzymes like nonspecific esterase, alpha-GPDH and SDH."} {"id": "PMID:169666", "title": "Unusual infections of the nervous system in malignant lymphomas.", "content": "Infection of the nervous system by toxoplasma, cytomegalovirus and varicella-zoster virus is described in three adult patients with malignant lymphoma. Morphologic identification of these organisms in otherwise nonspecific lesions is emphasized. Since such intercurrent infections are not usually diagnosed clinically in debiliated patients, their recognition at autopsy is important, particularly in view of the wide spread distribution of these organisms in normal population.", "contents": "Unusual infections of the nervous system in malignant lymphomas. Infection of the nervous system by toxoplasma, cytomegalovirus and varicella-zoster virus is described in three adult patients with malignant lymphoma. Morphologic identification of these organisms in otherwise nonspecific lesions is emphasized. Since such intercurrent infections are not usually diagnosed clinically in debiliated patients, their recognition at autopsy is important, particularly in view of the wide spread distribution of these organisms in normal population."} {"id": "PMID:169664", "title": "[Primary and secondary glioblastoma. Distinction by glutamate dehydrogenase activity].", "content": "The study by bistochemical method of some dehydrogenases in 74 glioblastoma multiforma permits to distinguish several metabolic groups. But if particular attention is payed to the activity of glutamate dehydrogenase, it is noted to be observed only in the small, dedifferentiated cells when the survival postoperative time was more than twelve months. As it is known that an operated glioblastoma does not survive more than one year, except if it is a secondary glioblastoma, it is concluded that the existence of this enzyme in those little cells permits to distinguish secondary from primitive glioblastoma.", "contents": "[Primary and secondary glioblastoma. Distinction by glutamate dehydrogenase activity]. The study by bistochemical method of some dehydrogenases in 74 glioblastoma multiforma permits to distinguish several metabolic groups. But if particular attention is payed to the activity of glutamate dehydrogenase, it is noted to be observed only in the small, dedifferentiated cells when the survival postoperative time was more than twelve months. As it is known that an operated glioblastoma does not survive more than one year, except if it is a secondary glioblastoma, it is concluded that the existence of this enzyme in those little cells permits to distinguish secondary from primitive glioblastoma."} {"id": "PMID:169665", "title": "[Necrotizing herpetic encephalitis. Electro-clinical and pathological studies on two infantile cases (author's transl)].", "content": "The electroclinical and pathological features of two infantile cases of acute necrotizing herpetic encephalitis are reported. The distribution of the lesions has been compared with those observed in fourteen other cases including four with EEG records. Various electroencephalographic features have been recorded including repetitive slow spikes and periodic stereotyped paroxysmal discharges. The pathological data are interpreted to attempt unravelling the physiopathology of the EEG features.", "contents": "[Necrotizing herpetic encephalitis. Electro-clinical and pathological studies on two infantile cases (author's transl)]. The electroclinical and pathological features of two infantile cases of acute necrotizing herpetic encephalitis are reported. The distribution of the lesions has been compared with those observed in fourteen other cases including four with EEG records. Various electroencephalographic features have been recorded including repetitive slow spikes and periodic stereotyped paroxysmal discharges. The pathological data are interpreted to attempt unravelling the physiopathology of the EEG features."} {"id": "PMID:169670", "title": "[Recent medical research on yoga and states of concentration].", "content": "Traditional oriental thinking attracts the growing scientific interest of occidental practitioners. Dr. Pierre Et\u00e9venon, head of the Department of Neuro-Psycho-Pharmacology at the French Institute for Health and Medical Research (INSERM), held several conversations and scientific exchanges with the author, and kindly provided copies of some of his works. They are at the basis of the present paper. M. A. Descamps (Paris) found that asanas--yoga postures-- are generators of dynamic action when there is an extension of the spinal column, whilst they lead to quiet states when there is a flexion of it. Claeys and Gones (Belgium) proved that overall global relaxation, as well as differential relaxation were far more effective and deep when obtained by yogis than those attempted by University students majoring in Physical Education. Lonsdorfer and Nussbaum (France) studied several parameters concerning hatha-yoga and concluded that it provides a regular functioning of the main bodily functions fostering thus a psycho-physical balance. Wallace and Benson (U.S.A.) proved that transcendental meditation increases aerobic metabolism, counteracting anaerobic metabolism which is related to mental distress. Et\u00e9venon (Paris) investigated neurophysiological effects of yoga in connection to ancient Indian concepts (Upanishads) on sleeping, meditation and degree of consciousness. Dr. Et\u00e9venon has studied the phylogenetic evolution of waking-sleeping cycles, focusing on phylogenetic and ontongenetic appearances of REM cycles (activated sleep). A correlation has been made with EEG studies during states of concentration (yoga, transcendental meditation, Zen). These states have been found to be specific brain activities, and different from deep sleep, in spite of certain similarities in the EEG. Several hypothesis are set forth to explain brain activities underlying sites of concentration. The possibilities of developing a conscious mastering of dreams are also under research, and special attention is paid to the works of Saint Denys (1867), and hindu tradition. This paper discusses also the psychological, therapeutic and anthropological implications of recent discoveries in the field.", "contents": "[Recent medical research on yoga and states of concentration]. Traditional oriental thinking attracts the growing scientific interest of occidental practitioners. Dr. Pierre Et\u00e9venon, head of the Department of Neuro-Psycho-Pharmacology at the French Institute for Health and Medical Research (INSERM), held several conversations and scientific exchanges with the author, and kindly provided copies of some of his works. They are at the basis of the present paper. M. A. Descamps (Paris) found that asanas--yoga postures-- are generators of dynamic action when there is an extension of the spinal column, whilst they lead to quiet states when there is a flexion of it. Claeys and Gones (Belgium) proved that overall global relaxation, as well as differential relaxation were far more effective and deep when obtained by yogis than those attempted by University students majoring in Physical Education. Lonsdorfer and Nussbaum (France) studied several parameters concerning hatha-yoga and concluded that it provides a regular functioning of the main bodily functions fostering thus a psycho-physical balance. Wallace and Benson (U.S.A.) proved that transcendental meditation increases aerobic metabolism, counteracting anaerobic metabolism which is related to mental distress. Et\u00e9venon (Paris) investigated neurophysiological effects of yoga in connection to ancient Indian concepts (Upanishads) on sleeping, meditation and degree of consciousness. Dr. Et\u00e9venon has studied the phylogenetic evolution of waking-sleeping cycles, focusing on phylogenetic and ontongenetic appearances of REM cycles (activated sleep). A correlation has been made with EEG studies during states of concentration (yoga, transcendental meditation, Zen). These states have been found to be specific brain activities, and different from deep sleep, in spite of certain similarities in the EEG. Several hypothesis are set forth to explain brain activities underlying sites of concentration. The possibilities of developing a conscious mastering of dreams are also under research, and special attention is paid to the works of Saint Denys (1867), and hindu tradition. This paper discusses also the psychological, therapeutic and anthropological implications of recent discoveries in the field."} {"id": "PMID:169671", "title": "The diagnostic value of hypothalamic-pituitary-adrenocortical function tests in patients with Cushing's syndrome.", "content": "The following examinations, including the estimation of urinary neutral steroid metabolites, plasma cortisol, the percentage of unbound-cortisol, cortisol production rate, plasma adrenocorticotrophin (ACTH), dexamethasone suppression test, ACTH stimulation test, metopirone test, lysine-vasopressin (LVP) test and insulin tolerance test, were conducted in 16 patients with Cushing's syndrome for the presence of hypercoticism and for identifying the cause of this syndrome. Of these tests, the measurements of plasma cortisol late in the day and single dose dexamethasone suppression test were most useful for the diagnosis of hypercorticism because of their reliability and simplicity. Urinary 17-KGS, THF/THE ratio, cortisol production rate and low dose dexamethasone suppression test were also useful, whereas insulin test and LVP test were less valuable for this purpose. For the identification of the causes of this syndrome, lysine vasopressin test and metopirone test were most reliable, and plasma ACTH was also useful for this purpose, whereas insulin test and ACTH stimulation test were less valuable.", "contents": "The diagnostic value of hypothalamic-pituitary-adrenocortical function tests in patients with Cushing's syndrome. The following examinations, including the estimation of urinary neutral steroid metabolites, plasma cortisol, the percentage of unbound-cortisol, cortisol production rate, plasma adrenocorticotrophin (ACTH), dexamethasone suppression test, ACTH stimulation test, metopirone test, lysine-vasopressin (LVP) test and insulin tolerance test, were conducted in 16 patients with Cushing's syndrome for the presence of hypercoticism and for identifying the cause of this syndrome. Of these tests, the measurements of plasma cortisol late in the day and single dose dexamethasone suppression test were most useful for the diagnosis of hypercorticism because of their reliability and simplicity. Urinary 17-KGS, THF/THE ratio, cortisol production rate and low dose dexamethasone suppression test were also useful, whereas insulin test and LVP test were less valuable for this purpose. For the identification of the causes of this syndrome, lysine vasopressin test and metopirone test were most reliable, and plasma ACTH was also useful for this purpose, whereas insulin test and ACTH stimulation test were less valuable."} {"id": "PMID:169672", "title": "Preparation of single cell suspensions from hepatoma cells in culture.", "content": "Fundamental examination was carried out on the liberation of single cells from hepatoma cells in culture. dRLa-74 cells derived from rat hepatoma, which hardly disperse as single cell suspensions with several proteolytic enzymes or EDTA alone, dispersed with a high yield of single cells by the combination of trypsin and EDTA. HUH-6 cells derived from human hepatoblastoma also showed similar results. The degree of cell dissociation by the combination was dependent on the incubation temperature or pH.", "contents": "Preparation of single cell suspensions from hepatoma cells in culture. Fundamental examination was carried out on the liberation of single cells from hepatoma cells in culture. dRLa-74 cells derived from rat hepatoma, which hardly disperse as single cell suspensions with several proteolytic enzymes or EDTA alone, dispersed with a high yield of single cells by the combination of trypsin and EDTA. HUH-6 cells derived from human hepatoblastoma also showed similar results. The degree of cell dissociation by the combination was dependent on the incubation temperature or pH."} {"id": "PMID:169673", "title": "Undifferentiated patterns of key glycolytic and gluconeogenic enzymes in epithelial cell lines derived from rat liver.", "content": "Established epithelial cell lines derived from livers of 7-day (B, B-R, B-3-4-7, J-C-1, J-C-13, J-5-2-1, E-C-4 and E-C-7) and adult (AL-2, AL-3, AL-4, AL-5 and AL-6) rats were analyzed for hexokinase (HK), pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glucose 6-phosphatase (G6Pase) and fructose 1,6-diphosphatase (FDPase). None of the cell lines showed appreciable activities of adult type liver enzymes (HK Type IVs (glucokinase), PK Type L, G6Pase and FDPase). On the contrary, the activities of fetal type liver enzymes (HK Types I and II, PK Type M2 and G6PD) increased markedly as compared with dispersed cells or tissues of adult liver. 6PGD gave minimum changes in activity, and the 6PGD/G6PD ratio decreased consistently. HK Type III was found only in J-C-13, AL-5 and AL-6, while HK Type IVf (high Km) was present in all the cell lines examined. Possible explanations for the undifferentiated patterns of carbohydrate-metabolizing enzymes in the established cell lines, which have several evidence of hepatocyte origin, are presented.", "contents": "Undifferentiated patterns of key glycolytic and gluconeogenic enzymes in epithelial cell lines derived from rat liver. Established epithelial cell lines derived from livers of 7-day (B, B-R, B-3-4-7, J-C-1, J-C-13, J-5-2-1, E-C-4 and E-C-7) and adult (AL-2, AL-3, AL-4, AL-5 and AL-6) rats were analyzed for hexokinase (HK), pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glucose 6-phosphatase (G6Pase) and fructose 1,6-diphosphatase (FDPase). None of the cell lines showed appreciable activities of adult type liver enzymes (HK Type IVs (glucokinase), PK Type L, G6Pase and FDPase). On the contrary, the activities of fetal type liver enzymes (HK Types I and II, PK Type M2 and G6PD) increased markedly as compared with dispersed cells or tissues of adult liver. 6PGD gave minimum changes in activity, and the 6PGD/G6PD ratio decreased consistently. HK Type III was found only in J-C-13, AL-5 and AL-6, while HK Type IVf (high Km) was present in all the cell lines examined. Possible explanations for the undifferentiated patterns of carbohydrate-metabolizing enzymes in the established cell lines, which have several evidence of hepatocyte origin, are presented."} {"id": "PMID:169674", "title": "Response of cat cerebellar vermis induced by sound. II. The role of the mossy and climbing fibers in acoustic transmission to the cerebellar cortex and influence of stimuli parameters.", "content": "Experiments were performed on cats under Chloralose or Nembutal anesthesia. The parameters of the acoustic click stimuli were found to have a strong influence on the responses registered from both the surface of the cerebellar vermis lobuli V up VII as well as from single units. It was shown that a stimulus frequency rate not greater than 1/2 s should be used, since higher frequencies caused strong attenuation of the response. The type of anesthesia did not change the latencies of reactions of both evoked potentials and single units. However, decreasing the strength of the click resulted in increased response latencies, in the case of single unit reactions. A very strong influence of weak visual stimuli on units was also observed. It is suggested that mossy fibers are the most important fibers in the transmission of acoustic information to the cerebellar cortex.", "contents": "Response of cat cerebellar vermis induced by sound. II. The role of the mossy and climbing fibers in acoustic transmission to the cerebellar cortex and influence of stimuli parameters. Experiments were performed on cats under Chloralose or Nembutal anesthesia. The parameters of the acoustic click stimuli were found to have a strong influence on the responses registered from both the surface of the cerebellar vermis lobuli V up VII as well as from single units. It was shown that a stimulus frequency rate not greater than 1/2 s should be used, since higher frequencies caused strong attenuation of the response. The type of anesthesia did not change the latencies of reactions of both evoked potentials and single units. However, decreasing the strength of the click resulted in increased response latencies, in the case of single unit reactions. A very strong influence of weak visual stimuli on units was also observed. It is suggested that mossy fibers are the most important fibers in the transmission of acoustic information to the cerebellar cortex."} {"id": "PMID:169683", "title": "Encephalomyocarditis (EMC) virus infection of the femoral vein of newborn mice.", "content": "The EMC virus was found to infect and injure the femoral veins of newborn mice. EMC viral crystals were found in the advential fibroblasts of these veins. In view of the extensive damage observed in the extremely small amount of tissue examined electron microscopically, the extent of the viral phlebitis must have been considerable. The relationship of these findings to the pathogenesis of thrombophlebitis in man provokes interesting speculations.", "contents": "Encephalomyocarditis (EMC) virus infection of the femoral vein of newborn mice. The EMC virus was found to infect and injure the femoral veins of newborn mice. EMC viral crystals were found in the advential fibroblasts of these veins. In view of the extensive damage observed in the extremely small amount of tissue examined electron microscopically, the extent of the viral phlebitis must have been considerable. The relationship of these findings to the pathogenesis of thrombophlebitis in man provokes interesting speculations."} {"id": "PMID:169685", "title": "Incorporation of the dietary trans fatty acid (C18:1) into the serum lipids, the serum lipoproteins and adipose tissue.", "content": "Two diets, identical except for differences in trans and cis fatty acids, were fed to rabbits in order to evaluate the effects of dietary trans fatty acids on the fatty acid composition of serum lipids, lipoproteins and adipose tissue. The animals were first starved to deplete adipose tissue stores and then were red a diet containing 15% of the calories as C18:1 trans fatty acid (elaidic acid). A second group received a diet containing an equivalent amount of C18:1 cis fatty acid (oleic acid). A third group of animals, the control group, was fed only the baseline low fat rabbit chow. Dietary trans fatty acid was incorporated into all serum lipid and lipoprotein fractions and into the adipose tissue. In the serum the triglycerides contained the greatest amount of trans fatty acid followed by the phospholipids with cholesterol esters containing the least. The trans fatty acids of the phospholipids and cholesterol esters were distributed equally among the lipoprotein fractions, but the triglycerides of high density lipoproteins contained less trans fatty acids than did the triglycerides of other lipoproteins. Adipose tissue developed a high content of C18:1 trans fatty acid (21.7%), apparently at the expense of C18:1 cis fatty acid. In addition to the incorporation of C18:1 trans fatty acid, the content of other fatty acids, including C18:2 and the total of C18:1 cis and trans, was influenced by the substitution of dietary trans for cis fatty acids. The serum phospholipids of the trans-fed rabbits contained more C18:2 than the phospholipids of the cis-fed rabbits. The serum cholesterol esters of the trans-fed rabbits contained more C18:2 and a smaller total of C18:1 (cis puls trans) than the cholesterol esters of the cis-fed rabbits. These differences indicated that C18:1 trans fatty acid was not necessarily the metabolic equivalent of 18:1 cis fatty acid. These results suggested that dietary trans fatty acids which are contained in hydrogenated margarines, shortenings and oils of the human diet are readily incorporated into the lipids of the body including membranous structures such as lipoproteins.", "contents": "Incorporation of the dietary trans fatty acid (C18:1) into the serum lipids, the serum lipoproteins and adipose tissue. Two diets, identical except for differences in trans and cis fatty acids, were fed to rabbits in order to evaluate the effects of dietary trans fatty acids on the fatty acid composition of serum lipids, lipoproteins and adipose tissue. The animals were first starved to deplete adipose tissue stores and then were red a diet containing 15% of the calories as C18:1 trans fatty acid (elaidic acid). A second group received a diet containing an equivalent amount of C18:1 cis fatty acid (oleic acid). A third group of animals, the control group, was fed only the baseline low fat rabbit chow. Dietary trans fatty acid was incorporated into all serum lipid and lipoprotein fractions and into the adipose tissue. In the serum the triglycerides contained the greatest amount of trans fatty acid followed by the phospholipids with cholesterol esters containing the least. The trans fatty acids of the phospholipids and cholesterol esters were distributed equally among the lipoprotein fractions, but the triglycerides of high density lipoproteins contained less trans fatty acids than did the triglycerides of other lipoproteins. Adipose tissue developed a high content of C18:1 trans fatty acid (21.7%), apparently at the expense of C18:1 cis fatty acid. In addition to the incorporation of C18:1 trans fatty acid, the content of other fatty acids, including C18:2 and the total of C18:1 cis and trans, was influenced by the substitution of dietary trans for cis fatty acids. The serum phospholipids of the trans-fed rabbits contained more C18:2 than the phospholipids of the cis-fed rabbits. The serum cholesterol esters of the trans-fed rabbits contained more C18:2 and a smaller total of C18:1 (cis puls trans) than the cholesterol esters of the cis-fed rabbits. These differences indicated that C18:1 trans fatty acid was not necessarily the metabolic equivalent of 18:1 cis fatty acid. These results suggested that dietary trans fatty acids which are contained in hydrogenated margarines, shortenings and oils of the human diet are readily incorporated into the lipids of the body including membranous structures such as lipoproteins."} {"id": "PMID:169686", "title": "Hepatocellular carcinoma and intermediate alpha1-antitrypsin deficiency (MZ phenotype).", "content": "A case history of a 16-year-old boy with hepatocellular carcinoma and an intermediate deficiency of alpha1-antitrypsin (MZ phenotype) is presented. Previous reports have suggested that hepatocellular carcinoma may be associated with the Z variant of antitrypsin and either a severe or intermediate antitrypsin deficiency. The present case is unusual because of the rather high level of the serum trypsin inhibitory capacity for an MZ heterozygote (1.633 units), which may be due to involvement of the liver by the tumor or to a recent partial hepatectomy. PAS-positive antitrypsin globules were seen in the primary tumor and in nodules metastatic to the mesentery, as well as in nonneoplastic portions of the liver. Hepatocellular carcinoma is another disease state that may occur preferentially in individuals with either severe or intermediate deficiencies of alpha1-antitrypsin.", "contents": "Hepatocellular carcinoma and intermediate alpha1-antitrypsin deficiency (MZ phenotype). A case history of a 16-year-old boy with hepatocellular carcinoma and an intermediate deficiency of alpha1-antitrypsin (MZ phenotype) is presented. Previous reports have suggested that hepatocellular carcinoma may be associated with the Z variant of antitrypsin and either a severe or intermediate antitrypsin deficiency. The present case is unusual because of the rather high level of the serum trypsin inhibitory capacity for an MZ heterozygote (1.633 units), which may be due to involvement of the liver by the tumor or to a recent partial hepatectomy. PAS-positive antitrypsin globules were seen in the primary tumor and in nodules metastatic to the mesentery, as well as in nonneoplastic portions of the liver. Hepatocellular carcinoma is another disease state that may occur preferentially in individuals with either severe or intermediate deficiencies of alpha1-antitrypsin."} {"id": "PMID:169687", "title": "Ex-hospital clients evaluate their aftercare experiences.", "content": "Seventy-two previously hospitalized clients of an inner-city community clinic, assigned to three treatment groups - medication-only, medication plus individual therapy, and medication plus therapy plus group experiences - evaluated their respective aftercare programs by responding to five questions. As compared with the others, medication-only clients were less inclined to see either the clinic or the medication as preventing rehospitalization, were alone in reporting that the clinic was responsible for preventing rehospitalization to the extent that the medication was effective, and responded to the question of rehospitalization by emphasizing worsening symptoms. Others emphasized therapy failure. Clients agreed with the professionals - aftercare should not be medication alone.", "contents": "Ex-hospital clients evaluate their aftercare experiences. Seventy-two previously hospitalized clients of an inner-city community clinic, assigned to three treatment groups - medication-only, medication plus individual therapy, and medication plus therapy plus group experiences - evaluated their respective aftercare programs by responding to five questions. As compared with the others, medication-only clients were less inclined to see either the clinic or the medication as preventing rehospitalization, were alone in reporting that the clinic was responsible for preventing rehospitalization to the extent that the medication was effective, and responded to the question of rehospitalization by emphasizing worsening symptoms. Others emphasized therapy failure. Clients agreed with the professionals - aftercare should not be medication alone."} {"id": "PMID:169688", "title": "Nosocomial and maternally acquired herpesvirus hominis infections. A report of four fatal cases in neonates.", "content": "Four fatal cases of neonatal herpes simplex infection occurred during a two-month period in the perinatal intensive care unit of a hospital. Virus isolation or serologic studies, or both, implicated herpesvirus hominis type 2 in all four cases. Three of the infants developed symptoms in the first week of life and were probably infected in utero or at delivery. The fourth infant did not develop signs of illness until age 6 weeks, an interval much longer than that expected with disease acquired at birth. An epidemiologic investigation indicated that the most likely source of this fourth infant's herpes infection was by indirect contact with one of the other three infected neonates. Nosocomial spread of herpes simplex virus within a hospital nursery, although uncommon, may pose an added risk to the newborn infant if nursery techniques among infants are compromised.", "contents": "Nosocomial and maternally acquired herpesvirus hominis infections. A report of four fatal cases in neonates. Four fatal cases of neonatal herpes simplex infection occurred during a two-month period in the perinatal intensive care unit of a hospital. Virus isolation or serologic studies, or both, implicated herpesvirus hominis type 2 in all four cases. Three of the infants developed symptoms in the first week of life and were probably infected in utero or at delivery. The fourth infant did not develop signs of illness until age 6 weeks, an interval much longer than that expected with disease acquired at birth. An epidemiologic investigation indicated that the most likely source of this fourth infant's herpes infection was by indirect contact with one of the other three infected neonates. Nosocomial spread of herpes simplex virus within a hospital nursery, although uncommon, may pose an added risk to the newborn infant if nursery techniques among infants are compromised."} {"id": "PMID:169689", "title": "Hypoglycemia in hypopituitary children.", "content": "Fifty-two children with growth hormone (GH) deficiency were examined for factors that might influence development of hypoglycemia. Symptomatic and asymptomatic hypoglycemia occurred with equal frequency in children with isolated GH and multiple anterior pituitary deficiencies. Of 52 children, nine (17%) had symptomatic hypoglycemia and 14 (27%) had asymptomatic hypoglycemia. Symptomatic hypoglycemia was more frequent in children who were both young (less than 4 years of age) and lean (elevated height age/weight age [HA/WA] ratio). With HGH therapy, these children had decreases in HA/WA ratios and improvement in carbohydrate homeostasis. Insulin responses to oral glucose and intravenous arginine administration were substantially lowered in children with symptomatic hypoglycemia, A deficiency of gluconeogenic substrate or impairment of amino acid mobilization may be a factor in the development of hypoglycemia in hypopituitarism similar to that postulated for ketotic hypoglycemia.", "contents": "Hypoglycemia in hypopituitary children. Fifty-two children with growth hormone (GH) deficiency were examined for factors that might influence development of hypoglycemia. Symptomatic and asymptomatic hypoglycemia occurred with equal frequency in children with isolated GH and multiple anterior pituitary deficiencies. Of 52 children, nine (17%) had symptomatic hypoglycemia and 14 (27%) had asymptomatic hypoglycemia. Symptomatic hypoglycemia was more frequent in children who were both young (less than 4 years of age) and lean (elevated height age/weight age [HA/WA] ratio). With HGH therapy, these children had decreases in HA/WA ratios and improvement in carbohydrate homeostasis. Insulin responses to oral glucose and intravenous arginine administration were substantially lowered in children with symptomatic hypoglycemia, A deficiency of gluconeogenic substrate or impairment of amino acid mobilization may be a factor in the development of hypoglycemia in hypopituitarism similar to that postulated for ketotic hypoglycemia."} {"id": "PMID:169691", "title": "Primary aldosteronism. A study in contrasts.", "content": "Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia.", "contents": "Primary aldosteronism. A study in contrasts. Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia."} {"id": "PMID:169692", "title": "Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis.", "content": "The level of serum angiotensin-converting enzyme (ACE) was elevated in 15 of 17 patients with active sarcoidosis. Serum ACE was studied to determine the effect of chronic lung disease upon the blood level of an enzyme believed to originate from the lungs. The assay was performed in approximately 200 control subjects and 200 patients with chronic lung disease using hippuryl-L-histidyl-L-leucine as substrate. Enzyme activity greater in male control subjects than in female subjects of comparable age and greater in children than in adults. Serum ACE was significantly reduced in patients with chronic obstructive lung disease, lung cancer, tuberculosis and cystic fibrosis, as compared to control subjects, and was even lower in those receiving corticosteroids. Of greatest interest, however, was that levels in patients with active sarcoidosis not receiving steroids were greater than 2 standard deviations above the mean for the adult control subjects (greater than 11.6 units) whereas levels in patients with sarcoidosis receiving steroids and in those with resolved disease were normal. A survey of subjects with other granulomatous diseases failed to reveal any other condition that was significantly associated with a similar elevation of serum ACE levels. Elevation of ACE levels in sarcoidosis appears to be associated with the active disease process and does not appear to be a familial inherited enzyme abnormality. An assay of serum ACE is a useful tool for regulating therapy in sarcoidosis and for confirming the diagnosis, since it readily distinguishes these patients from others with tuberculosis, lung cancer or lymphoma.", "contents": "Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. The level of serum angiotensin-converting enzyme (ACE) was elevated in 15 of 17 patients with active sarcoidosis. Serum ACE was studied to determine the effect of chronic lung disease upon the blood level of an enzyme believed to originate from the lungs. The assay was performed in approximately 200 control subjects and 200 patients with chronic lung disease using hippuryl-L-histidyl-L-leucine as substrate. Enzyme activity greater in male control subjects than in female subjects of comparable age and greater in children than in adults. Serum ACE was significantly reduced in patients with chronic obstructive lung disease, lung cancer, tuberculosis and cystic fibrosis, as compared to control subjects, and was even lower in those receiving corticosteroids. Of greatest interest, however, was that levels in patients with active sarcoidosis not receiving steroids were greater than 2 standard deviations above the mean for the adult control subjects (greater than 11.6 units) whereas levels in patients with sarcoidosis receiving steroids and in those with resolved disease were normal. A survey of subjects with other granulomatous diseases failed to reveal any other condition that was significantly associated with a similar elevation of serum ACE levels. Elevation of ACE levels in sarcoidosis appears to be associated with the active disease process and does not appear to be a familial inherited enzyme abnormality. An assay of serum ACE is a useful tool for regulating therapy in sarcoidosis and for confirming the diagnosis, since it readily distinguishes these patients from others with tuberculosis, lung cancer or lymphoma."} {"id": "PMID:169693", "title": "Immunology of sarcoidosis.", "content": "The cardinal immunologic changes in sarcoidosis consist of depression of delayed-type hypersensitivity, hyperreactive circulating antibody responses and the Kveim-Siltzbach skin test phenomenon. Depression of delayed-type hypersensitivity is demonstrated by skin tests using tuberculin, mumps, pertussis, trichophytin, oidiomycin, dinitrochlorobenzene and Californian keyhole limpet hemocyanin. The cultured lymphocytes from patients with depression of delayed-type hypersensitivity react poorly to phytohemagglutinin, and there is a close correlation between anergy of lymphocytes in culture and by cutaneous anergy. In vivo cutaneous anergy mirrors in vitro cellular hyporeactivity. Other technics used to expose immunologic defects in peripheral lymphocytes of patients with sarcoidosis include tests of T and B cell function, rosetie formation and migration inhibition. Whereas there is cutaneous anergy and impaired cellular immunity in patients with sarcoidosis, the reverse holds for circulating factors. There are increased circulating immunoglobulin levels, increased circulating antibody levels to Epstein-Barr, herpes simplex, rubella, measles and parainfluenza viruses, increase antibody response to mismatched blood and occasional false-positive Wassermann reactions, but there is no increase in circulating autoan tibodies. There is no evidence that patients with sarcoidosis belong predominantly to any particular histocompatibility locus. Worldwide figures for the Kveim-Siltzbach skin test are presented. They provide evidence of its specificity in various international series. The causes of nonspecific reactions are discussed.", "contents": "Immunology of sarcoidosis. The cardinal immunologic changes in sarcoidosis consist of depression of delayed-type hypersensitivity, hyperreactive circulating antibody responses and the Kveim-Siltzbach skin test phenomenon. Depression of delayed-type hypersensitivity is demonstrated by skin tests using tuberculin, mumps, pertussis, trichophytin, oidiomycin, dinitrochlorobenzene and Californian keyhole limpet hemocyanin. The cultured lymphocytes from patients with depression of delayed-type hypersensitivity react poorly to phytohemagglutinin, and there is a close correlation between anergy of lymphocytes in culture and by cutaneous anergy. In vivo cutaneous anergy mirrors in vitro cellular hyporeactivity. Other technics used to expose immunologic defects in peripheral lymphocytes of patients with sarcoidosis include tests of T and B cell function, rosetie formation and migration inhibition. Whereas there is cutaneous anergy and impaired cellular immunity in patients with sarcoidosis, the reverse holds for circulating factors. There are increased circulating immunoglobulin levels, increased circulating antibody levels to Epstein-Barr, herpes simplex, rubella, measles and parainfluenza viruses, increase antibody response to mismatched blood and occasional false-positive Wassermann reactions, but there is no increase in circulating autoan tibodies. There is no evidence that patients with sarcoidosis belong predominantly to any particular histocompatibility locus. Worldwide figures for the Kveim-Siltzbach skin test are presented. They provide evidence of its specificity in various international series. The causes of nonspecific reactions are discussed."} {"id": "PMID:169695", "title": "Hereditary cataracts in deer mice (Peromyscus maniculatus).", "content": "A new type of hereditary cataract was predicted in the deer mouse (Peromyscus maniculatus) by the presence of syndactyly of the hind feet. Early morphologic changes were found in the equatorial cells that differentiated into new lens fibers. Later swelling at the anterior and posterior poles of these cells produced lens opacities. Anterior and posterior subcapsular cataracts progressed to a hypermature shrunken lens.", "contents": "Hereditary cataracts in deer mice (Peromyscus maniculatus). A new type of hereditary cataract was predicted in the deer mouse (Peromyscus maniculatus) by the presence of syndactyly of the hind feet. Early morphologic changes were found in the equatorial cells that differentiated into new lens fibers. Later swelling at the anterior and posterior poles of these cells produced lens opacities. Anterior and posterior subcapsular cataracts progressed to a hypermature shrunken lens."} {"id": "PMID:169696", "title": "A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.", "content": "A 23-year-old man had slow psychomotor development at 6 months of age and developed intermittent corneal clouding at about 18 months. He developed a truncal ataxia and hypotonia of the limbs combined with spasticity and active deep reflexes that did not progress. His skeleton and facies were normal. Between 1 and 13 years of age, he developed severe optic atrophy, absence of retinal blood vessels, and an extinguished electroretinogram. Biochemical analysis of cultured fibroblasts indicated no lysosomal hydrolase deficiency; cellular metachromasia was absent and there was no mucopolysaccharidoses. Ultrastructural studies indicated single-membrane-limited vacuoles containing lamellated membranes and a polymorphous substance in tissue-cultured cells and conjunctiva.", "contents": "A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration. A 23-year-old man had slow psychomotor development at 6 months of age and developed intermittent corneal clouding at about 18 months. He developed a truncal ataxia and hypotonia of the limbs combined with spasticity and active deep reflexes that did not progress. His skeleton and facies were normal. Between 1 and 13 years of age, he developed severe optic atrophy, absence of retinal blood vessels, and an extinguished electroretinogram. Biochemical analysis of cultured fibroblasts indicated no lysosomal hydrolase deficiency; cellular metachromasia was absent and there was no mucopolysaccharidoses. Ultrastructural studies indicated single-membrane-limited vacuoles containing lamellated membranes and a polymorphous substance in tissue-cultured cells and conjunctiva."} {"id": "PMID:169697", "title": "The influence of prostaglandin endoperoxides on platelet ultrastructure.", "content": "Prostaglandin endoperoxides produced during aggregation of blood platelets are potent promoters of platelet aggregation and the release reaction. The present investigation has studied the effects of prostaglandin endoperoxides produced by platelet microsomes after incubation with arachidonic acid on the ultrastructure of platelets. Prostaglandin endoperoxides caused platelet pseudopod formation and internal transformation associated with a contractile wave within the platelet. The contractile process was similar to that seen following incubation of platelets with collagen or thrombin but was more complete than that seen with 25 muM ADP. Platelet aggregation was more prominent in unstirred samples incubated with the prostaglandin endoperoxides than in samples similarly incubated with 25 muM ADP. Dilatation of the open canalicular system was not a prominent feature except at 45 minutes after addition of the endoperoxides to the platelets, when the platelets appeared to be in a recovery phase. We conclude that the endoperoxides promote platelet stickiness and platelet aggregation by directly or indirectly stimulating the platelet contractile system.", "contents": "The influence of prostaglandin endoperoxides on platelet ultrastructure. Prostaglandin endoperoxides produced during aggregation of blood platelets are potent promoters of platelet aggregation and the release reaction. The present investigation has studied the effects of prostaglandin endoperoxides produced by platelet microsomes after incubation with arachidonic acid on the ultrastructure of platelets. Prostaglandin endoperoxides caused platelet pseudopod formation and internal transformation associated with a contractile wave within the platelet. The contractile process was similar to that seen following incubation of platelets with collagen or thrombin but was more complete than that seen with 25 muM ADP. Platelet aggregation was more prominent in unstirred samples incubated with the prostaglandin endoperoxides than in samples similarly incubated with 25 muM ADP. Dilatation of the open canalicular system was not a prominent feature except at 45 minutes after addition of the endoperoxides to the platelets, when the platelets appeared to be in a recovery phase. We conclude that the endoperoxides promote platelet stickiness and platelet aggregation by directly or indirectly stimulating the platelet contractile system."} {"id": "PMID:169698", "title": "The course and nature of acinar cell death following pancreatic ligation in the guinea pig.", "content": "The course and nature of acinar cell death (ACD) following pancreatic ligation in the guinea pig was studied as a possible model for human disease. Ultrastructural studies after various periods of ligation suggested a biphasic pattern of ACD. Early phase ACD involved only a small portion of acinar cells and occurred within a few hours of ligation. It was preceded by swelling and vesiculation of the rough endoplasmic reticulum. Morphometric measurements disclosed celular swelling at this time, and NaCl equilibration studies demonstrated a change in cellular osmoregulation. Late phase ACD, characterized by cellular wasting and autophagic vacuole formation, became prominent several days after ligation. Marked increases in lysosomal enzyme activities were found in tissue homogenates at this time, and acid phosphatase electron histochemistry localized the majority of this increased activity to lysosomes and autophagic vacuoles within the acinar cells. The etiology and nature of both phases of ACD are discussed.", "contents": "The course and nature of acinar cell death following pancreatic ligation in the guinea pig. The course and nature of acinar cell death (ACD) following pancreatic ligation in the guinea pig was studied as a possible model for human disease. Ultrastructural studies after various periods of ligation suggested a biphasic pattern of ACD. Early phase ACD involved only a small portion of acinar cells and occurred within a few hours of ligation. It was preceded by swelling and vesiculation of the rough endoplasmic reticulum. Morphometric measurements disclosed celular swelling at this time, and NaCl equilibration studies demonstrated a change in cellular osmoregulation. Late phase ACD, characterized by cellular wasting and autophagic vacuole formation, became prominent several days after ligation. Marked increases in lysosomal enzyme activities were found in tissue homogenates at this time, and acid phosphatase electron histochemistry localized the majority of this increased activity to lysosomes and autophagic vacuoles within the acinar cells. The etiology and nature of both phases of ACD are discussed."} {"id": "PMID:169699", "title": "Production of ferritin by rat hepatoma cells in vitro. Demonstration of protein subunits and ferritin by immunofluorescence.", "content": "Using precipitating antibodies to ACI rat liver ferritin and to sodium-dodecyl-sulfate-dissociated protein subunits of ACI rat liver ferritin, we have demonstrated the presence of ferritin-positive sites and subunit-positive sites in situ in several rat hepatoma cell lines by immunofluorescence. Hepatoma cells from three transplantable rat hepatomas (Reuber H-139, Reuber H-35, and Morris 5123) were explanted and propagated. Rabbit antibodies specific for either protein subunits of ferritin or ferritin were prepared by affinity chromatography or by dissociation of antibody-antigen complexes with 0.1 M acetic acid followed by differential ultracentrifugation. Explants of Reuber H-139, Reuber H-35, and Morris 5123 hepatoma cells, grown either in ordinary McCoy's 5a medium or in such medium enriched with iron (0.002% Fe), gave positive immunofluorescence for subunits as well as ferritin. Exposure of a clonal strain of Morris 5123 hepatoma cells to iron-enriched culture medium for varying lengths of time of up to 24 hours resulted in progressive increase in the quantity of ferritin-specific immunofluorescent cytoplasmic material, which was at first present diffusely, and later in clumps. By contrast, during the initial 24-hour period, subunit-specific immunofluorescence remained at relatively low intensity, with diffuse distribution through the cytoplasma. Our findings indicate a) the presence, in the cytoplasm, of the three kinds of hepatoma cells, of unassembled or only partly assembled subunits of fragments of subunits as well as of ferritin, and b) rapid assembly of the protein subunits into apoferritin and ferritin after administration of iron, so that the concentration of subunits in the cytoplasm was not significantly increased.", "contents": "Production of ferritin by rat hepatoma cells in vitro. Demonstration of protein subunits and ferritin by immunofluorescence. Using precipitating antibodies to ACI rat liver ferritin and to sodium-dodecyl-sulfate-dissociated protein subunits of ACI rat liver ferritin, we have demonstrated the presence of ferritin-positive sites and subunit-positive sites in situ in several rat hepatoma cell lines by immunofluorescence. Hepatoma cells from three transplantable rat hepatomas (Reuber H-139, Reuber H-35, and Morris 5123) were explanted and propagated. Rabbit antibodies specific for either protein subunits of ferritin or ferritin were prepared by affinity chromatography or by dissociation of antibody-antigen complexes with 0.1 M acetic acid followed by differential ultracentrifugation. Explants of Reuber H-139, Reuber H-35, and Morris 5123 hepatoma cells, grown either in ordinary McCoy's 5a medium or in such medium enriched with iron (0.002% Fe), gave positive immunofluorescence for subunits as well as ferritin. Exposure of a clonal strain of Morris 5123 hepatoma cells to iron-enriched culture medium for varying lengths of time of up to 24 hours resulted in progressive increase in the quantity of ferritin-specific immunofluorescent cytoplasmic material, which was at first present diffusely, and later in clumps. By contrast, during the initial 24-hour period, subunit-specific immunofluorescence remained at relatively low intensity, with diffuse distribution through the cytoplasma. Our findings indicate a) the presence, in the cytoplasm, of the three kinds of hepatoma cells, of unassembled or only partly assembled subunits of fragments of subunits as well as of ferritin, and b) rapid assembly of the protein subunits into apoferritin and ferritin after administration of iron, so that the concentration of subunits in the cytoplasm was not significantly increased."} {"id": "PMID:169700", "title": "Quantitative study on the effect of an ACTH-producing pituitary tumor on the ultrastructure of the mouse adrenal gland.", "content": "The ultrastructure of the adrenal cortex was studied by quantitative stereologic techniques in LAF1 mice bearing a transplantable, ACTH-secreting pituitary tumor (AtT). The tumor stimulated a significant increase in volume and surface area of smooth endoplasmic reticulum and mitochondrial membranes in all three zones of the adrenal cortex. Concomitantly, plasma corticosterone was increased significantly in tumor-bearing animals. The AtT was an adenoma of the chromophobe type. Continuity of the nuclear membrane with the rough endoplasmic reticulum was readily observed in tumor parenchymal cells.", "contents": "Quantitative study on the effect of an ACTH-producing pituitary tumor on the ultrastructure of the mouse adrenal gland. The ultrastructure of the adrenal cortex was studied by quantitative stereologic techniques in LAF1 mice bearing a transplantable, ACTH-secreting pituitary tumor (AtT). The tumor stimulated a significant increase in volume and surface area of smooth endoplasmic reticulum and mitochondrial membranes in all three zones of the adrenal cortex. Concomitantly, plasma corticosterone was increased significantly in tumor-bearing animals. The AtT was an adenoma of the chromophobe type. Continuity of the nuclear membrane with the rough endoplasmic reticulum was readily observed in tumor parenchymal cells."} {"id": "PMID:169701", "title": "The lead line in bone---a lesion apparently due to chondroclastic indigestion.", "content": "The metaphyseal line of increased radiodensity which occurs in lead poisoning was studied in children and young monkeys with lead encephalopathy and in guinea pigs. The histologic lesion consists of impaired resorption of calcified metaphyseal cartilage, depressed bone deposition on cartilaginous surfaces, and the accumulation of numerous multinucleate giant cells, some containing lead inclusions. By electron microscopy, the giant cells appear to be osteoclasts and chondroclasts containing large amounts of mineralized cartilage matrix. We interpret the lead line to be the result of a lead-induced inability of cartilage-resorbing cells to degrade mineralized matrix, with a resultant impairment of metaphyseal cartilage resorption. The radiodensity of the lead line would thus be due to persistent mineralized metaphyseal cartilage and not to a primary osseous change. Some observations on lead inclusions in these cells suggest that the fibrillar component forms before the amorphous part.", "contents": "The lead line in bone---a lesion apparently due to chondroclastic indigestion. The metaphyseal line of increased radiodensity which occurs in lead poisoning was studied in children and young monkeys with lead encephalopathy and in guinea pigs. The histologic lesion consists of impaired resorption of calcified metaphyseal cartilage, depressed bone deposition on cartilaginous surfaces, and the accumulation of numerous multinucleate giant cells, some containing lead inclusions. By electron microscopy, the giant cells appear to be osteoclasts and chondroclasts containing large amounts of mineralized cartilage matrix. We interpret the lead line to be the result of a lead-induced inability of cartilage-resorbing cells to degrade mineralized matrix, with a resultant impairment of metaphyseal cartilage resorption. The radiodensity of the lead line would thus be due to persistent mineralized metaphyseal cartilage and not to a primary osseous change. Some observations on lead inclusions in these cells suggest that the fibrillar component forms before the amorphous part."} {"id": "PMID:169703", "title": "Coronary artery cyclic AMP content during adrenergic receptor stimulation.", "content": "The purpose of this study was to test the hypothesis that the mechanical response of coronary smooth muscle following adrenergic receptor stimulation was mediated by changes in cyclic AMP content. Dibutyryl cyclic AMP caused relaxation of coronary artery strips. Aminophyline caused relaxation and a 254% elevation of cyclic AMP content (P less than 0.005). Phenylephrine caused contraction but no significant change in cyclic AMP content (P greater than 0.4). Epinephrine alone caused contraction and a 99% elevation of cyclic AMP content (P less than 0.001). The alpha blocker, phentolamine, reversed the mechanicaal response to epinephrine, but it did not significantly (P greater than 0.15) reduce the effect of epinephrine on cyclic AMP content. Propranolol enhanced the contractile response to epinephrine and attenuated the epinephrine-induced increase in cyclic AMP content. These results suggest that the contraction of coronary arteries associated with alpha-receptor stimulation is not mediated by changes in cyclic AMP content; however, relaxation associated with beta-receptor stimulation may be mediated by an increase in cyclic AMP content.", "contents": "Coronary artery cyclic AMP content during adrenergic receptor stimulation. The purpose of this study was to test the hypothesis that the mechanical response of coronary smooth muscle following adrenergic receptor stimulation was mediated by changes in cyclic AMP content. Dibutyryl cyclic AMP caused relaxation of coronary artery strips. Aminophyline caused relaxation and a 254% elevation of cyclic AMP content (P less than 0.005). Phenylephrine caused contraction but no significant change in cyclic AMP content (P greater than 0.4). Epinephrine alone caused contraction and a 99% elevation of cyclic AMP content (P less than 0.001). The alpha blocker, phentolamine, reversed the mechanicaal response to epinephrine, but it did not significantly (P greater than 0.15) reduce the effect of epinephrine on cyclic AMP content. Propranolol enhanced the contractile response to epinephrine and attenuated the epinephrine-induced increase in cyclic AMP content. These results suggest that the contraction of coronary arteries associated with alpha-receptor stimulation is not mediated by changes in cyclic AMP content; however, relaxation associated with beta-receptor stimulation may be mediated by an increase in cyclic AMP content."} {"id": "PMID:169704", "title": "Estimation of cyclic AMP turnover in normal and methylprednisolone-treated dogs: effect of catecholamines.", "content": "The turnover rate of plasma cAMP was measured in unanesthetized normal and methylprednisolone (MP)-treated dogs with [8-3H]cAMP. Determination of specific activity was based on saturation of the specific binding protein, thus bypassing the need to know the plasma level of cAMP. In normal dogs the infusion of epinephrine increased plasma glucose by 33% and both the plasma level and rate of appearance (Ra) of cAMP 2.5-fold. Treatment with MP decreased the concentration as well as the turnover rate of cAMP by about 50%. It greatly potentiated not only the hyperglycemic effect (4-fold) of epinephrine but also the rise of plasma cAMP (8.5-fold) and that of Ra (6.8-fold). Norepinephrine infusion increased cAMP only by 50%. This effect was not potentiated by MP treatment and not altered by Na nicotinate. There was a linear correlation between plasma cAMP concentration and the rate of disappearance (Rd) of cAMP. It is concluded that: a) the increase of hepatic glycogenolysis is accompanied by a rise of cAMP output, whereas that of lipolysis is not; b) glucocorticoid treatment affects cAMP turnover; and c) the plasma level of cAMP is controlled by Ra, whereas Rd is the result of the mass-action effect of the concentration.", "contents": "Estimation of cyclic AMP turnover in normal and methylprednisolone-treated dogs: effect of catecholamines. The turnover rate of plasma cAMP was measured in unanesthetized normal and methylprednisolone (MP)-treated dogs with [8-3H]cAMP. Determination of specific activity was based on saturation of the specific binding protein, thus bypassing the need to know the plasma level of cAMP. In normal dogs the infusion of epinephrine increased plasma glucose by 33% and both the plasma level and rate of appearance (Ra) of cAMP 2.5-fold. Treatment with MP decreased the concentration as well as the turnover rate of cAMP by about 50%. It greatly potentiated not only the hyperglycemic effect (4-fold) of epinephrine but also the rise of plasma cAMP (8.5-fold) and that of Ra (6.8-fold). Norepinephrine infusion increased cAMP only by 50%. This effect was not potentiated by MP treatment and not altered by Na nicotinate. There was a linear correlation between plasma cAMP concentration and the rate of disappearance (Rd) of cAMP. It is concluded that: a) the increase of hepatic glycogenolysis is accompanied by a rise of cAMP output, whereas that of lipolysis is not; b) glucocorticoid treatment affects cAMP turnover; and c) the plasma level of cAMP is controlled by Ra, whereas Rd is the result of the mass-action effect of the concentration."} {"id": "PMID:169705", "title": "Hypercholesterolemia of total starvation: its mechanism via tissue mobilization of cholesterol.", "content": "After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero.", "contents": "Hypercholesterolemia of total starvation: its mechanism via tissue mobilization of cholesterol. After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero."} {"id": "PMID:169708", "title": "Hepatoma associated with anabolic steroid therapy.", "content": "A patient with Fanconi's anemia who developed a hepatoma after 50 months of therapy with anabolic steroids is reported. The lesion presented as a cold focal defect on a Tc99m sulfur colloid scintigram, but was avascular on dynamic scintigraphy. Both the unusual avascularity of the hepatoma, and its association with anabolic steriod therapy are discussed.", "contents": "Hepatoma associated with anabolic steroid therapy. A patient with Fanconi's anemia who developed a hepatoma after 50 months of therapy with anabolic steroids is reported. The lesion presented as a cold focal defect on a Tc99m sulfur colloid scintigram, but was avascular on dynamic scintigraphy. Both the unusual avascularity of the hepatoma, and its association with anabolic steriod therapy are discussed."} {"id": "PMID:169709", "title": "[Electron microscopic investigations of vitreous collagen after treating the vitreous with liquefying substances (author's transl)].", "content": "By electron microscopic studies collagenase, hyaluronidase, HCl, ascorbic acid, and iron ions have been found to attack the collagen fibers of bovine vitreous. Because of the possible role of ascorbic acid in collagen synthesis and the ability of ascorbic acid to degrade hyaluronic acid and collagen we suggest that the ascorbic acid of the vitreous essentially participates in construction and metabolism of the vitreous body.", "contents": "[Electron microscopic investigations of vitreous collagen after treating the vitreous with liquefying substances (author's transl)]. By electron microscopic studies collagenase, hyaluronidase, HCl, ascorbic acid, and iron ions have been found to attack the collagen fibers of bovine vitreous. Because of the possible role of ascorbic acid in collagen synthesis and the ability of ascorbic acid to degrade hyaluronic acid and collagen we suggest that the ascorbic acid of the vitreous essentially participates in construction and metabolism of the vitreous body."} {"id": "PMID:169715", "title": "On the function of sleep.", "content": "It is proposed that sleep serves the function of maintaining immobility in animals at times when immobility is an optimum behavioural survival strategem. Sleep is of great evolutionary age and is always carefully tailored to the life-style of each animal; abundant in some species and absent from others. The survival advantages conferred on an animal by the power of sleep to schedule behaviour effectively may justify its existence and persistence in the evolution of species.", "contents": "On the function of sleep. It is proposed that sleep serves the function of maintaining immobility in animals at times when immobility is an optimum behavioural survival strategem. Sleep is of great evolutionary age and is always carefully tailored to the life-style of each animal; abundant in some species and absent from others. The survival advantages conferred on an animal by the power of sleep to schedule behaviour effectively may justify its existence and persistence in the evolution of species."} {"id": "PMID:169716", "title": "Mammary cancer in the dog: a study of 120 cases.", "content": "Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated.", "contents": "Mammary cancer in the dog: a study of 120 cases. Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated."} {"id": "PMID:169719", "title": "The chemotaxis of selected cell types to connective tissue degradation products.", "content": "Because rheumatoid inflammation is associated with the presence of large numbers of leukocytes in joint effusions, the question of whether enzymatic splitting of collagen and fibrin can lead to generation of chemotactic factors was investigated. Fibrinogen was purified from the plasma of four different species, and the homogeneity of the preparations was established by physicochemical and immunologic techniques. Fibrin was prepared and then lysed with plasmin to obtain fibrin degradation products (FDP). Similarly, purified collagenase was used to lyse collagen in vitro, and the chemotactic activity of the reaction mixtures was analyzed. The experiments presented indicate that fibrinogen, fibrin, and plasmin do not possess any intrinsic chemotactic activity. However, when fibrin was split by plasmin, FDP of human, bovine, sheep, and equine origin all proved to be strong leukotactic agents for polymorphonuclear leukocytes (PMN). Purified collagenase per se was found to be a cell type-specific chemotactic agent for PMN. Not only were collagen degradation products not chemotactic, but they also inhibited the leukotactic activity of the purified collagenase. Furthermore, this inhibition of the chemotactic activity of collagenase was independent of its enzymatic activity. The results presented suggest that there is a direct correlation between the process of fibrinolysis and the chemotactic attraction of leukocytes and between the presence of collagenase and leukotaxis. This system may serve as a model to explain the mechanisms by which cells accumulate in inflamed joints.", "contents": "The chemotaxis of selected cell types to connective tissue degradation products. Because rheumatoid inflammation is associated with the presence of large numbers of leukocytes in joint effusions, the question of whether enzymatic splitting of collagen and fibrin can lead to generation of chemotactic factors was investigated. Fibrinogen was purified from the plasma of four different species, and the homogeneity of the preparations was established by physicochemical and immunologic techniques. Fibrin was prepared and then lysed with plasmin to obtain fibrin degradation products (FDP). Similarly, purified collagenase was used to lyse collagen in vitro, and the chemotactic activity of the reaction mixtures was analyzed. The experiments presented indicate that fibrinogen, fibrin, and plasmin do not possess any intrinsic chemotactic activity. However, when fibrin was split by plasmin, FDP of human, bovine, sheep, and equine origin all proved to be strong leukotactic agents for polymorphonuclear leukocytes (PMN). Purified collagenase per se was found to be a cell type-specific chemotactic agent for PMN. Not only were collagen degradation products not chemotactic, but they also inhibited the leukotactic activity of the purified collagenase. Furthermore, this inhibition of the chemotactic activity of collagenase was independent of its enzymatic activity. The results presented suggest that there is a direct correlation between the process of fibrinolysis and the chemotactic attraction of leukocytes and between the presence of collagenase and leukotaxis. This system may serve as a model to explain the mechanisms by which cells accumulate in inflamed joints."} {"id": "PMID:169722", "title": "Prostaglandins in the rheumatic diseases.", "content": "The prostaglandins may participate in the pathogenesis of the inflammatory rheumatic diseases by acting as mediators of inflammation and in promoting bone resorption. Levels of PGB (presumed to arise from PGE) in synovial fluids are elevated in the majority of a group of patients with inflammatory rheumatic diseases, as compared to similar patients treated with aspirin and indomethacin and patients with osteoarthritis. Rheumatoid synovium produces large amounts of PGE2 in organ culture. In addition, fibroblast cell lines derived from rheumatoid synovia synthesize more PGE and more cAMP than do cells from normal synovia or skin. The media from rheumatoid synovial organ cultures contain large quantities of bone-resorbing activity toward mouse calvaria in vitro. The bone resorption can be accounted for by PGE2 produced by the synovia, because the activity and PG synthesis are inhibited by more than 90% by incubation of the tissue with indomethacin, because it is quantitatively extractable into ether, and because it bears a relationship to the concentrations of PGE2 present, as measured by radioimmunoassay.", "contents": "Prostaglandins in the rheumatic diseases. The prostaglandins may participate in the pathogenesis of the inflammatory rheumatic diseases by acting as mediators of inflammation and in promoting bone resorption. Levels of PGB (presumed to arise from PGE) in synovial fluids are elevated in the majority of a group of patients with inflammatory rheumatic diseases, as compared to similar patients treated with aspirin and indomethacin and patients with osteoarthritis. Rheumatoid synovium produces large amounts of PGE2 in organ culture. In addition, fibroblast cell lines derived from rheumatoid synovia synthesize more PGE and more cAMP than do cells from normal synovia or skin. The media from rheumatoid synovial organ cultures contain large quantities of bone-resorbing activity toward mouse calvaria in vitro. The bone resorption can be accounted for by PGE2 produced by the synovia, because the activity and PG synthesis are inhibited by more than 90% by incubation of the tissue with indomethacin, because it is quantitatively extractable into ether, and because it bears a relationship to the concentrations of PGE2 present, as measured by radioimmunoassay."} {"id": "PMID:169725", "title": "[Mechanism of hyocorticosteronemia action of Strongyloides ratti in the rat].", "content": "In order to explain the hypocorticosteronemia which establishes itself in rats with Strongyloides ratti parasites, we are proceeding with a functional exploration of the hypothalamo-hypophyso-corticosurrenal axis in experimentally infested rodents. The adreno-cortico-tropic-hormone test (A.C.T.H.), stress to ether and the Lysin-8-Vasopressin and Metopirone tests lead to concordant results: -- the hypothalamo-pituitary-corticosurrenal present a functional integrity which allows it to react normally to direct stimulation or to feed-back; -- the deficiency seems to relate to the hypothalamic secretion of the cortico-releasing factor; -- the cause would stem from an inhibition of the nervous mechanism which regulates this neurosecretion.", "contents": "[Mechanism of hyocorticosteronemia action of Strongyloides ratti in the rat]. In order to explain the hypocorticosteronemia which establishes itself in rats with Strongyloides ratti parasites, we are proceeding with a functional exploration of the hypothalamo-hypophyso-corticosurrenal axis in experimentally infested rodents. The adreno-cortico-tropic-hormone test (A.C.T.H.), stress to ether and the Lysin-8-Vasopressin and Metopirone tests lead to concordant results: -- the hypothalamo-pituitary-corticosurrenal present a functional integrity which allows it to react normally to direct stimulation or to feed-back; -- the deficiency seems to relate to the hypothalamic secretion of the cortico-releasing factor; -- the cause would stem from an inhibition of the nervous mechanism which regulates this neurosecretion."} {"id": "PMID:169728", "title": "Detection of agents that alter the bacterial cell surface.", "content": "Proteus mirabilis is not killed by polymyxin B, normal serum, or sodium deoxycholate. Exposure to polymyxin B renders the cells susceptible to killing by the latter two agents. The data suggest that this synergism is due to polymyxin B-induced surface changes. The results point out an inadequacy of existing methods of screening for antibiotics; they fail to detect agents which, while showing no in vitro effect on growth, may alter a resistant organism so that it becomes more susceptible to other antimicrobials or host defense mechanisms. A method is described which can be used to detect such cell surface-modifying agents.", "contents": "Detection of agents that alter the bacterial cell surface. Proteus mirabilis is not killed by polymyxin B, normal serum, or sodium deoxycholate. Exposure to polymyxin B renders the cells susceptible to killing by the latter two agents. The data suggest that this synergism is due to polymyxin B-induced surface changes. The results point out an inadequacy of existing methods of screening for antibiotics; they fail to detect agents which, while showing no in vitro effect on growth, may alter a resistant organism so that it becomes more susceptible to other antimicrobials or host defense mechanisms. A method is described which can be used to detect such cell surface-modifying agents."} {"id": "PMID:169726", "title": "Non-myogenic tumors involving skeletal muscle. A survey with special reference to alveolar soft part sarcoma.", "content": "Skeletal muscle is remarkably free of neoplasms despite its great body mass. Metastatic tumors to skeletal muscle are distinctly uncommon. Primary myogenous tumors (defined as those whose cytoplasm contains myofibrils) are infrequent, compared to primary lesions of supporting stroma and vascular origin. Almost all non-myogenic tumors of striated muscle occur also in other areas of the body and many represent extension from contiguous structures. The distinctive non-myogenic tumor which occurs exclusively in skeletal muscle, alveolar soft part sarcoma, has ultrastrucutral features of a secretory lesion with distinctive membrane bound crystalloids which may be lipid in nature. The ultrastructural features of alveolar soft part sarcoma do not support a myogenous derivation.", "contents": "Non-myogenic tumors involving skeletal muscle. A survey with special reference to alveolar soft part sarcoma. Skeletal muscle is remarkably free of neoplasms despite its great body mass. Metastatic tumors to skeletal muscle are distinctly uncommon. Primary myogenous tumors (defined as those whose cytoplasm contains myofibrils) are infrequent, compared to primary lesions of supporting stroma and vascular origin. Almost all non-myogenic tumors of striated muscle occur also in other areas of the body and many represent extension from contiguous structures. The distinctive non-myogenic tumor which occurs exclusively in skeletal muscle, alveolar soft part sarcoma, has ultrastrucutral features of a secretory lesion with distinctive membrane bound crystalloids which may be lipid in nature. The ultrastructural features of alveolar soft part sarcoma do not support a myogenous derivation."} {"id": "PMID:169729", "title": "Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa.", "content": "Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.", "contents": "Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa. Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic."} {"id": "PMID:169727", "title": "Diagnostic value of cytologic specimens obtained from children with cancer.", "content": "The practical value of cytologic examination in the clinical management of children with cancer was determined by analyzing 2,363 cytologic specimens collected during a two year period. The specimens included cerebrospinal fluid, pleural and peritoneal effusions, urine and tracheal aspirates from 347 children with cancer. Malignant tumor cells were detected in 266 specimens obtained from 106 children with the following malignant neoplasms: leukemia 44/133, malignant lymphoma 13/64, soft tissue sarcoma 13/48, neuroblastoma 13/26, Wilms' tumor 4/18, malignant teratoma 4/13, osteogenic sarcoma 7/11, Ewing's sarcoma 2/10, brain tumor 5/6 and retinoblastoma 1/1. No malignant cells were detected in fluids from 18 patients with other tumors. The malignant cells were identified most ofter in spinal fluid, pleural and peritoneal effusions. Cytologic examination appears to be of value in the clinical management of children with cancer.", "contents": "Diagnostic value of cytologic specimens obtained from children with cancer. The practical value of cytologic examination in the clinical management of children with cancer was determined by analyzing 2,363 cytologic specimens collected during a two year period. The specimens included cerebrospinal fluid, pleural and peritoneal effusions, urine and tracheal aspirates from 347 children with cancer. Malignant tumor cells were detected in 266 specimens obtained from 106 children with the following malignant neoplasms: leukemia 44/133, malignant lymphoma 13/64, soft tissue sarcoma 13/48, neuroblastoma 13/26, Wilms' tumor 4/18, malignant teratoma 4/13, osteogenic sarcoma 7/11, Ewing's sarcoma 2/10, brain tumor 5/6 and retinoblastoma 1/1. No malignant cells were detected in fluids from 18 patients with other tumors. The malignant cells were identified most ofter in spinal fluid, pleural and peritoneal effusions. Cytologic examination appears to be of value in the clinical management of children with cancer."} {"id": "PMID:169730", "title": "Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B.", "content": "Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular material, possibly nucleic acids and/or ribosomes. These aggregations were only produced by minimum inhibitory or higher concentrations of the antibiotic as shown with Salmonella and Escherichia strains differing in their polymyxin susceptibility. The outer membrane of Salmonella typhimurium revealed characteristic blebs when treated with polymyxin B. This was investigated by the gentle methods of spray-freezing and freeze-etching. The obtained electron micrographs suggest that the polymyxin-induced blebs are projections of the outer monolayer of the outer membrane. A possible mechanism of penetration of polymyxin B through the cell envelope of gram-negative bacteria is presented.", "contents": "Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B. Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular material, possibly nucleic acids and/or ribosomes. These aggregations were only produced by minimum inhibitory or higher concentrations of the antibiotic as shown with Salmonella and Escherichia strains differing in their polymyxin susceptibility. The outer membrane of Salmonella typhimurium revealed characteristic blebs when treated with polymyxin B. This was investigated by the gentle methods of spray-freezing and freeze-etching. The obtained electron micrographs suggest that the polymyxin-induced blebs are projections of the outer monolayer of the outer membrane. A possible mechanism of penetration of polymyxin B through the cell envelope of gram-negative bacteria is presented."} {"id": "PMID:169731", "title": "Removal of enteroviruses from sewage by bench-scale rotary-tube trickling filters.", "content": "The efficacy of a rotary-tube type of trickling filter for removing coxsackievirus A9, poliovirus 1, and echovirus 12 suspended in raw settled sewage was investigated. At filtration rates equivalent to about 10 MGD (million gallons per day)/acre (ca. 3,785 m3/day per acre), the filters removed 95% of the poliovirus, 83% of echovirus 12, and 94% of coxsackievirus A9. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals were remarkably similar, averaging 94, 92, 93, and 95%, respectively. At filtration rates equivalent to about 23 MGD/acre, 59% of the poliovirus, 63% of the echovirus 23, and 81% of the coxsackievirus A9 were removed. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals at this filtration rate were 68, 75, 72, and 56%, respectively. Viruses were assumed to be adsorbed to the biological slime growing in the filters, but attempts to disassociate the viruses from the slime were unsuccessful, indicating that the slime-virus complex is very stable or that the viruses were somehow inactivated. The data indicate that coliform and fecal streptococci reductions in this type sewage treatment process can be used as an index of virus reduction. Disinfection, however, must be used to ensure a virus-free final effluent.", "contents": "Removal of enteroviruses from sewage by bench-scale rotary-tube trickling filters. The efficacy of a rotary-tube type of trickling filter for removing coxsackievirus A9, poliovirus 1, and echovirus 12 suspended in raw settled sewage was investigated. At filtration rates equivalent to about 10 MGD (million gallons per day)/acre (ca. 3,785 m3/day per acre), the filters removed 95% of the poliovirus, 83% of echovirus 12, and 94% of coxsackievirus A9. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals were remarkably similar, averaging 94, 92, 93, and 95%, respectively. At filtration rates equivalent to about 23 MGD/acre, 59% of the poliovirus, 63% of the echovirus 23, and 81% of the coxsackievirus A9 were removed. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals at this filtration rate were 68, 75, 72, and 56%, respectively. Viruses were assumed to be adsorbed to the biological slime growing in the filters, but attempts to disassociate the viruses from the slime were unsuccessful, indicating that the slime-virus complex is very stable or that the viruses were somehow inactivated. The data indicate that coliform and fecal streptococci reductions in this type sewage treatment process can be used as an index of virus reduction. Disinfection, however, must be used to ensure a virus-free final effluent."} {"id": "PMID:169732", "title": "Microbiological hazards of household toilets: droplet production and the fate of residual organisms.", "content": "Large numbers of bacteria and viruses when seeded into household toilets were shown to remain in the bowl after flushing, and even continual flushing could not remove a persistent fraction. This was found to be due to the adsorption of the organsims to the porcelain surfaces of the bowl, with gradual elution occuring after each flush. Droplets produced by flushing toilets were found to harbor both bacteria and viruses which had been seeded. The detection of bacteria and firuses falling out onto surfaces in bathrooms after flushing indicated that they remain airborne long enough to settle on surfaces throughout the bathroom. Thus, there is a possibility that a person may acquire an infection from an aerosol produced by a toilet.", "contents": "Microbiological hazards of household toilets: droplet production and the fate of residual organisms. Large numbers of bacteria and viruses when seeded into household toilets were shown to remain in the bowl after flushing, and even continual flushing could not remove a persistent fraction. This was found to be due to the adsorption of the organsims to the porcelain surfaces of the bowl, with gradual elution occuring after each flush. Droplets produced by flushing toilets were found to harbor both bacteria and viruses which had been seeded. The detection of bacteria and firuses falling out onto surfaces in bathrooms after flushing indicated that they remain airborne long enough to settle on surfaces throughout the bathroom. Thus, there is a possibility that a person may acquire an infection from an aerosol produced by a toilet."} {"id": "PMID:169733", "title": "Survival of human enteric and other sewage microorganisms under simulated deep-sea conditions.", "content": "The survival of pure cultures of Escherichia coli, Streptococcus faecalis, Clostridium perfringens, and Vibrio parahaemolyticus under simulated deep-sea conditions of low temperature (4 C), seawater, and hydrostatic pressures ranging from 1 to 1,000 atm was determined over a period exceeding 300 h. The viability of E. coli and total aerobic bacteria in seawater-diluted raw sewage subjected to these deep-sea conditions was also measured. There was a greater survival of both E. coli and S. faecalis at 250 and 500 atm than at 1 atm at 4 C. S. faecalis was quite insensitive to 1,000 atm, whereas with E. coli there was a 10-fold die-off per 50-h exposure to 1,000 atm. In contrast, V. parahaemolyticus and C. perfringens were quite sensitive to pressures exceeding 250 atm, and with both of these species there was a total loss of viability of approximately 10(8) cells per ml within 100 h at 1,000 arm and within 200 h at 500 atm. The viability of the naturally occurring fecal coliforms in sewage exposed to moderate pressures at 4 C was found to be similar to the survival patterns demonstrated with pure cultures of E. coli. The total numbers of aerobic bacteria in these sewage samples, however, stabilized at 500 and 1,000 atm after 100 h, and at 1 and 250 atm there was significant growth of sewage-associated bacteria, which apparently utilized the organic compounds in the seawater-diluted sewage samples. A preliminary classification of some of these bacteria indicated that approximately 90% (160 isolates) of the organisms that survived over a 400-h exposure to 500 and 1,000 atm were Arthrobacter/Corynebacterium species, and the representative organisms capable of growing at 1 and 250 atm in seawater at 4 C were gram-positive cellulose digesters and an unidentified gram-negative coccus. The significance of these results with respect to the contamination of the deep ocean with human pathogens and the possibility of sewage-associated microorganisms growing and competing with indigenous marine microbial flora in situ is discussed.", "contents": "Survival of human enteric and other sewage microorganisms under simulated deep-sea conditions. The survival of pure cultures of Escherichia coli, Streptococcus faecalis, Clostridium perfringens, and Vibrio parahaemolyticus under simulated deep-sea conditions of low temperature (4 C), seawater, and hydrostatic pressures ranging from 1 to 1,000 atm was determined over a period exceeding 300 h. The viability of E. coli and total aerobic bacteria in seawater-diluted raw sewage subjected to these deep-sea conditions was also measured. There was a greater survival of both E. coli and S. faecalis at 250 and 500 atm than at 1 atm at 4 C. S. faecalis was quite insensitive to 1,000 atm, whereas with E. coli there was a 10-fold die-off per 50-h exposure to 1,000 atm. In contrast, V. parahaemolyticus and C. perfringens were quite sensitive to pressures exceeding 250 atm, and with both of these species there was a total loss of viability of approximately 10(8) cells per ml within 100 h at 1,000 arm and within 200 h at 500 atm. The viability of the naturally occurring fecal coliforms in sewage exposed to moderate pressures at 4 C was found to be similar to the survival patterns demonstrated with pure cultures of E. coli. The total numbers of aerobic bacteria in these sewage samples, however, stabilized at 500 and 1,000 atm after 100 h, and at 1 and 250 atm there was significant growth of sewage-associated bacteria, which apparently utilized the organic compounds in the seawater-diluted sewage samples. A preliminary classification of some of these bacteria indicated that approximately 90% (160 isolates) of the organisms that survived over a 400-h exposure to 500 and 1,000 atm were Arthrobacter/Corynebacterium species, and the representative organisms capable of growing at 1 and 250 atm in seawater at 4 C were gram-positive cellulose digesters and an unidentified gram-negative coccus. The significance of these results with respect to the contamination of the deep ocean with human pathogens and the possibility of sewage-associated microorganisms growing and competing with indigenous marine microbial flora in situ is discussed."} {"id": "PMID:169734", "title": "Inhibition of Clostridium botulinum by strains of Clostridium perfringens isolated from soil.", "content": "Thirty-one soil samples were examined for the presence of organisms capable of inhibiting growth and toxin production of strains of Clostridium botulinum type A. Such organisms were found in eight samples of soil. Inhibiting strains of C. perfringens were found in five samples, of C. sporogenes in three and of Bacillus cereus in three. Three of the C. perfringens strains produced an inhibitor effective on all 11 strains of C. botulinum type A against which they were tested, seven of eight proteolytic type B strains, one nonproteolytic type B strain, five of nine type E strains and all seven type F strains, whether proteolytic or nonproteolytic. They did not inhibit any of 26 type C strains, 6 type D strains, 4 type E strains, or 24 C. sporogenes strains. In mixed culture, an inhibitor strain of C. perfringens repressed growth and toxin production by a C. botulinum type A strain even though it was outnumbered by the latter about 40 times. It also repressed growth and toxin production of C. botulinum in mixed culture of soils in which this latter organism naturally occurred when cooked meat medium but not when trypticase medium was used.", "contents": "Inhibition of Clostridium botulinum by strains of Clostridium perfringens isolated from soil. Thirty-one soil samples were examined for the presence of organisms capable of inhibiting growth and toxin production of strains of Clostridium botulinum type A. Such organisms were found in eight samples of soil. Inhibiting strains of C. perfringens were found in five samples, of C. sporogenes in three and of Bacillus cereus in three. Three of the C. perfringens strains produced an inhibitor effective on all 11 strains of C. botulinum type A against which they were tested, seven of eight proteolytic type B strains, one nonproteolytic type B strain, five of nine type E strains and all seven type F strains, whether proteolytic or nonproteolytic. They did not inhibit any of 26 type C strains, 6 type D strains, 4 type E strains, or 24 C. sporogenes strains. In mixed culture, an inhibitor strain of C. perfringens repressed growth and toxin production by a C. botulinum type A strain even though it was outnumbered by the latter about 40 times. It also repressed growth and toxin production of C. botulinum in mixed culture of soils in which this latter organism naturally occurred when cooked meat medium but not when trypticase medium was used."} {"id": "PMID:169751", "title": "Nitrosyl-hemoglobin formation in the blood of animals exposed to nitric oxide.", "content": "Animals were exposed to nitric oxide (NO) in order to study its biological effect. First a method was developed to exclude nitrogen dioxide formed during exposure of NO. Nitrosyl-hemoglobin (NOHb) in the blood of mice, rats, and rabbits exposed to NO was determined by electron spin resonance spectrometry at -100C. The content of NOHb in the blood of the mouse reached the maximum (0.13% of the total hemoglobin) 20 minutes after the exposure was begun and thereafter a state of equilibrium was maintained. The NOHv level decreased to one half in several minutes after the mouse was removed to a filtered air environment. Dose-response relationship was observed between gas concentrations and the maximum NOHb level.", "contents": "Nitrosyl-hemoglobin formation in the blood of animals exposed to nitric oxide. Animals were exposed to nitric oxide (NO) in order to study its biological effect. First a method was developed to exclude nitrogen dioxide formed during exposure of NO. Nitrosyl-hemoglobin (NOHb) in the blood of mice, rats, and rabbits exposed to NO was determined by electron spin resonance spectrometry at -100C. The content of NOHb in the blood of the mouse reached the maximum (0.13% of the total hemoglobin) 20 minutes after the exposure was begun and thereafter a state of equilibrium was maintained. The NOHv level decreased to one half in several minutes after the mouse was removed to a filtered air environment. Dose-response relationship was observed between gas concentrations and the maximum NOHb level."} {"id": "PMID:169753", "title": "Evaluation of craniofacial surgery in the treatment of facial deformities.", "content": "Surgical access to the cranial, orbital, and facial areas, as developed by Tessier, has produced not only definitive repair of previously uncorrectable congenital deformities such as orbital hypertelorism and facial stenosis (e.g., Crouzon's, Apert's syndromes) but also has improved markedly the treatment of traumatic and neoplastic defects. The surgical approach allows complete dissection of facial soft tisses including the orbits from the underlying bones followed by corrective osteotomies and fixation. Mobilization of the frontal lobes through a frontal bone flap exposure may be required. The ramifications of this latest intrusion by surgeons into a previously inviolate anatomic area have involved neurosurgeons, ophthalmologists, anesthesiologists, and dental and psycho-social disciplines. The disciplines of genetics and embryology are being influenced by this new field of surgery, much as the study of immunology was influenced by transplantation surgery two decades ago. This report analyzes a 10 year experience with over 100 patients with emphasis on patient selection by disease, age, intellectual status, morbidity, complications, and the psycho-social reactions of patient and family. Procedures initially planned to correct dental and aesthetic defects are proving beneficial for other functions including hearing, taste and smell, articulation and tongue movement, respiratory function, vision, and possibly bone growth. The development of self image, a normal process always in operation, is also strikingly altered. These operations may last as long as 14 to 16 hours. We have had no deaths or postoperative blindness. One postoperative cerebrospinal fluid leak was successfully repaired. Three partial losses of bone grafts and four instances of late cellulitis have occurred. Prevention of infection seems related to avoidance of dead spaces and primary closure of all mucosal, dural, conjunctival and skin surfaces.", "contents": "Evaluation of craniofacial surgery in the treatment of facial deformities. Surgical access to the cranial, orbital, and facial areas, as developed by Tessier, has produced not only definitive repair of previously uncorrectable congenital deformities such as orbital hypertelorism and facial stenosis (e.g., Crouzon's, Apert's syndromes) but also has improved markedly the treatment of traumatic and neoplastic defects. The surgical approach allows complete dissection of facial soft tisses including the orbits from the underlying bones followed by corrective osteotomies and fixation. Mobilization of the frontal lobes through a frontal bone flap exposure may be required. The ramifications of this latest intrusion by surgeons into a previously inviolate anatomic area have involved neurosurgeons, ophthalmologists, anesthesiologists, and dental and psycho-social disciplines. The disciplines of genetics and embryology are being influenced by this new field of surgery, much as the study of immunology was influenced by transplantation surgery two decades ago. This report analyzes a 10 year experience with over 100 patients with emphasis on patient selection by disease, age, intellectual status, morbidity, complications, and the psycho-social reactions of patient and family. Procedures initially planned to correct dental and aesthetic defects are proving beneficial for other functions including hearing, taste and smell, articulation and tongue movement, respiratory function, vision, and possibly bone growth. The development of self image, a normal process always in operation, is also strikingly altered. These operations may last as long as 14 to 16 hours. We have had no deaths or postoperative blindness. One postoperative cerebrospinal fluid leak was successfully repaired. Three partial losses of bone grafts and four instances of late cellulitis have occurred. Prevention of infection seems related to avoidance of dead spaces and primary closure of all mucosal, dural, conjunctival and skin surfaces."} {"id": "PMID:169754", "title": "The prediction of hormonal dependency of mammary cancer.", "content": "The estrogen receptor protein (estrophilin) was determined in specimens from 359 primary breast cancers and from metastatic tumors of 214 patients. Ninety-eight patients were eventually treated by some form of endocrine therapy: 82 patients were treated by ablative therapy, and 16 by hormonal additive treatment. The records of 81 of the 98 patients whose tumors were characterized for estrogen receptor content and who had received some type of endocrine therapy were reviewed by a peer review group that assessed the objective data for these patients regarding objective remission or failure to treatment. A positive estrophilin determination was defined as receptor content greater than 250 fmole per gram of tumor for premenopausal females and greater than 750 fmole per gram of tumor for postmenopausal and previously castrated patients. Estrogen receptor determinations may be made from tumor specimens as small as 200 mg. Sixty-nine patients underwent some form of ablative therapy. Twenty-seven of these patients were found to have significant receptor determinations. Of those patients in whom a definite determination was made of their post-treatment response, roughly two-thirds experienced objective remissions. None of the 42 patients with negative estrogen receptor determination experienced an objective remission to ablative endocrine therapy. Only one of 6 patients with negative determinations benefited from additive hormonal therapy; 4 of 6 patients with positive determinations benefited from additive therapy. Not all women with receptor containing mammary cancer will respond favorably to endocrine therapy, but those patients whose tumors lack a critical amount of estrophilin have little chance of benefit from either endocrine ablation or hormone administration. The estrogen receptor content of the primary tumor indicates the hormonal dependency of the tumor and may be used to predict the response to endocrine treatment when recurrent disease appears.", "contents": "The prediction of hormonal dependency of mammary cancer. The estrogen receptor protein (estrophilin) was determined in specimens from 359 primary breast cancers and from metastatic tumors of 214 patients. Ninety-eight patients were eventually treated by some form of endocrine therapy: 82 patients were treated by ablative therapy, and 16 by hormonal additive treatment. The records of 81 of the 98 patients whose tumors were characterized for estrogen receptor content and who had received some type of endocrine therapy were reviewed by a peer review group that assessed the objective data for these patients regarding objective remission or failure to treatment. A positive estrophilin determination was defined as receptor content greater than 250 fmole per gram of tumor for premenopausal females and greater than 750 fmole per gram of tumor for postmenopausal and previously castrated patients. Estrogen receptor determinations may be made from tumor specimens as small as 200 mg. Sixty-nine patients underwent some form of ablative therapy. Twenty-seven of these patients were found to have significant receptor determinations. Of those patients in whom a definite determination was made of their post-treatment response, roughly two-thirds experienced objective remissions. None of the 42 patients with negative estrogen receptor determination experienced an objective remission to ablative endocrine therapy. Only one of 6 patients with negative determinations benefited from additive hormonal therapy; 4 of 6 patients with positive determinations benefited from additive therapy. Not all women with receptor containing mammary cancer will respond favorably to endocrine therapy, but those patients whose tumors lack a critical amount of estrophilin have little chance of benefit from either endocrine ablation or hormone administration. The estrogen receptor content of the primary tumor indicates the hormonal dependency of the tumor and may be used to predict the response to endocrine treatment when recurrent disease appears."} {"id": "PMID:169755", "title": "Effect of thymectomy on zoxazolamine paralysis and metabolism in untreated and (PCN) pregnenolone-16alpha-carbonitril- or ACTH-pretreated rats.", "content": "The effect of thymectomy on zoxazolamine paralysis and metabolism was investigated in young female untreated and PCN- or ACTH-pretreated rats. Thymectomy performed at least 24 hr before injection of zoxazolamine significantly prolonges paralysis time. Pretreatment with PCN (an inducer of hepatic microsomal enzymes) or ACTH (known to alter protein binding and excretion of zoxazolamine) shortened paralysis in thymectomized animals; but only in comparison to thymus ablated controls. The surgical intervention seemed to decrease the metabolism of zoxazolamine in the 9,000g supernatant fraction of the liver.", "contents": "Effect of thymectomy on zoxazolamine paralysis and metabolism in untreated and (PCN) pregnenolone-16alpha-carbonitril- or ACTH-pretreated rats. The effect of thymectomy on zoxazolamine paralysis and metabolism was investigated in young female untreated and PCN- or ACTH-pretreated rats. Thymectomy performed at least 24 hr before injection of zoxazolamine significantly prolonges paralysis time. Pretreatment with PCN (an inducer of hepatic microsomal enzymes) or ACTH (known to alter protein binding and excretion of zoxazolamine) shortened paralysis in thymectomized animals; but only in comparison to thymus ablated controls. The surgical intervention seemed to decrease the metabolism of zoxazolamine in the 9,000g supernatant fraction of the liver."} {"id": "PMID:169756", "title": "Effect of methadone on the male reproductive system.", "content": "Daily injections (s.c.) of methadone HCL (5, 10 or 20 mg/kg) for 5 or 10 days caused significant regression (p less than or equal to 0.05) in the weights of sex accessory organs and testes in mature mice. Similar treatment regimens led to significant elevations in the levels of cyclic adenosine monophosphate (cAMP) in the prostate gland (P less than or equal to 0.05). Daily injuctions of morphine sulfate (10, 20 or 40 mg/kg) likewise caused significant increases in cAMP levels in the prostate gland (P less than or equal to 0.05). When either of these drugs were incubated in vitro with prostate glands obtained from normal mice, the cAMP levels were also observed to be elevated (P less than or equal to 0.05). The results reveal that so-called analgesic drugs can exert deleterious actions upon male reproductive tissues in the mouse.", "contents": "Effect of methadone on the male reproductive system. Daily injections (s.c.) of methadone HCL (5, 10 or 20 mg/kg) for 5 or 10 days caused significant regression (p less than or equal to 0.05) in the weights of sex accessory organs and testes in mature mice. Similar treatment regimens led to significant elevations in the levels of cyclic adenosine monophosphate (cAMP) in the prostate gland (P less than or equal to 0.05). Daily injuctions of morphine sulfate (10, 20 or 40 mg/kg) likewise caused significant increases in cAMP levels in the prostate gland (P less than or equal to 0.05). When either of these drugs were incubated in vitro with prostate glands obtained from normal mice, the cAMP levels were also observed to be elevated (P less than or equal to 0.05). The results reveal that so-called analgesic drugs can exert deleterious actions upon male reproductive tissues in the mouse."} {"id": "PMID:169758", "title": "Further studies on the effect of cyclic nucleotides on testis DNA synthesis.", "content": "The inhibitory effect of dibutyryl cyclic AMP (dbcAPM) on in vitro rat testis DNA synthesis appears to be relatively specific in nature. Of 7 organs studied, only testis and kidney in vitro DNA synthesis was significantly affected. In addition, another cyclic nucleotide, dibutyryl cyclic GMP (by dbc AMP), had no effect on in vitro testis DNA synthesis. This was true whether testis tissue was mature or immature. Similarly, by dbcAMP had no significant effect on in vitro testicular protein or RNA synthesis. The inhibition of in vitro testicular DNA synthesis by dbcAMP occurs while 3H-cAMP is accumulating in testis tissue. dbcGMP was found to have no antagonistic effect towards the inhibitory effect of dbcAMP on in vitro testis DNA synthesis.", "contents": "Further studies on the effect of cyclic nucleotides on testis DNA synthesis. The inhibitory effect of dibutyryl cyclic AMP (dbcAPM) on in vitro rat testis DNA synthesis appears to be relatively specific in nature. Of 7 organs studied, only testis and kidney in vitro DNA synthesis was significantly affected. In addition, another cyclic nucleotide, dibutyryl cyclic GMP (by dbc AMP), had no effect on in vitro testis DNA synthesis. This was true whether testis tissue was mature or immature. Similarly, by dbcAMP had no significant effect on in vitro testicular protein or RNA synthesis. The inhibition of in vitro testicular DNA synthesis by dbcAMP occurs while 3H-cAMP is accumulating in testis tissue. dbcGMP was found to have no antagonistic effect towards the inhibitory effect of dbcAMP on in vitro testis DNA synthesis."} {"id": "PMID:169759", "title": "[Antibodies in patients with cervicouterine carcinoma].", "content": "Cervical smears and serum samples were obtained from 28 ABO compatible patients with carcinoma of the cervix (CaCx) in O to IV clinical stages. Serum IgG antibodies against autologous CaCx cells were detected by immunofluorescence reactions in 24/24 patients with carcinoma of the cervix in I to IV clinical stages. These antibodies also reacted against alogeneic CaCx cells 53/54. Negative reactions were obtained n 4/4 cases of carcinoma of the cervix in stage O, and in control group, 10 normal persons and in 33 neoplastic sera from patients with other malignancies. Hence, detection of serum antibodies against CaCx cells could be an additional tool for CaCx detection.", "contents": "[Antibodies in patients with cervicouterine carcinoma]. Cervical smears and serum samples were obtained from 28 ABO compatible patients with carcinoma of the cervix (CaCx) in O to IV clinical stages. Serum IgG antibodies against autologous CaCx cells were detected by immunofluorescence reactions in 24/24 patients with carcinoma of the cervix in I to IV clinical stages. These antibodies also reacted against alogeneic CaCx cells 53/54. Negative reactions were obtained n 4/4 cases of carcinoma of the cervix in stage O, and in control group, 10 normal persons and in 33 neoplastic sera from patients with other malignancies. Hence, detection of serum antibodies against CaCx cells could be an additional tool for CaCx detection."} {"id": "PMID:169761", "title": "[Neonatal lactic acidosis and hypoglycemia due to a congenital hepatic fructose-1,6-diphosphatase deficiency].", "content": "Famialial defect of hepatic fructose-1,6-diphosphatase. Diagnosis was suspected in a male newborn since a brother was also concerned by the disease. The disease may be therefore diagnosed early, when the onset is neonatal. In the neonatal distress syndromes due to hereditery disorders of metabolism, a semiologic field may be isolated in which symptoms begin after an interval of short duration with hypoglycemia, hepatomegaly, lactic acidosis and ketosis (\"enlarged liver hypoglycemia\"). This possibility leads first to a symptomatic treatment of hypoglycemia and acidoketosis, then to the feeding with human milk and simple functional tests for the diagnostic approach.", "contents": "[Neonatal lactic acidosis and hypoglycemia due to a congenital hepatic fructose-1,6-diphosphatase deficiency]. Famialial defect of hepatic fructose-1,6-diphosphatase. Diagnosis was suspected in a male newborn since a brother was also concerned by the disease. The disease may be therefore diagnosed early, when the onset is neonatal. In the neonatal distress syndromes due to hereditery disorders of metabolism, a semiologic field may be isolated in which symptoms begin after an interval of short duration with hypoglycemia, hepatomegaly, lactic acidosis and ketosis (\"enlarged liver hypoglycemia\"). This possibility leads first to a symptomatic treatment of hypoglycemia and acidoketosis, then to the feeding with human milk and simple functional tests for the diagnostic approach."} {"id": "PMID:169762", "title": "Activity of some enzymes which synthesize and metabolize catecholamines in the brain and peripheral organs in developing rats.", "content": "Activities of monoamine oxidase (MAO), DOPA-decarboxylase (DD), phenoletha-nolamine-N-methyltransferase (PNMT) and phosphodiesterase (PDE) were studied in the brain and its parts, heart, kidneys, adrenals and liver in developing rats. In vitro, the action of nialamid on MAO activity in the liver, RO-4-4602 on DD activity in the liver, and D(-) INPEA on PNMT activity in the adrenals was investigated. The influence of 6-hydroxydopamine (6-OHDA), 200 mg/kg i. p., on MAO activity in the liver of developing rats was also studied. Irregular changes in activities of examined enzymes during development were observed. 6-OHDA, nialamid and RO-4-4602 inhibited enzyme activities in young rats more strongly than in adult animals.", "contents": "Activity of some enzymes which synthesize and metabolize catecholamines in the brain and peripheral organs in developing rats. Activities of monoamine oxidase (MAO), DOPA-decarboxylase (DD), phenoletha-nolamine-N-methyltransferase (PNMT) and phosphodiesterase (PDE) were studied in the brain and its parts, heart, kidneys, adrenals and liver in developing rats. In vitro, the action of nialamid on MAO activity in the liver, RO-4-4602 on DD activity in the liver, and D(-) INPEA on PNMT activity in the adrenals was investigated. The influence of 6-hydroxydopamine (6-OHDA), 200 mg/kg i. p., on MAO activity in the liver of developing rats was also studied. Irregular changes in activities of examined enzymes during development were observed. 6-OHDA, nialamid and RO-4-4602 inhibited enzyme activities in young rats more strongly than in adult animals."} {"id": "PMID:169763", "title": "Action of biogenic amines injected intracerebrally on duration of hexobarbital-induced sleep in rats.", "content": "The influence of intracerebrally injected biogenic amines and cyclic AMP dibutyrate on duration of sleep induced with hexobarbital (50 mg/kg i.v.) in rats was studied. Duration of sleep was markedly prolonged by adrenaline, noradrenaline, dopamine, 5-hydroxydopamine and acetylcholine. Cyclic AMP dibutyrate injected 30 minutes before hexobarbital shortened time of sleep. The role of biogenic amines in hexobarbital-induced sleep is discussed.", "contents": "Action of biogenic amines injected intracerebrally on duration of hexobarbital-induced sleep in rats. The influence of intracerebrally injected biogenic amines and cyclic AMP dibutyrate on duration of sleep induced with hexobarbital (50 mg/kg i.v.) in rats was studied. Duration of sleep was markedly prolonged by adrenaline, noradrenaline, dopamine, 5-hydroxydopamine and acetylcholine. Cyclic AMP dibutyrate injected 30 minutes before hexobarbital shortened time of sleep. The role of biogenic amines in hexobarbital-induced sleep is discussed."} {"id": "PMID:169764", "title": "[Cytomegaly and central nervous system abnormalities. Report of 2 cases associated with agenesia of the corpus callosum and cystic encephalopathy].", "content": "Two cases of cytomegaly of the central nervous system of infants, disclosing typical viral inclusions in the brain tissues, associated with agenesia of the corpus callosum and cystic symmetrical post-infarction encephalopathy are reported. It is suggested that the callosal defect was caused by cystic degeneration occuring within the lamina reuniens and the prematurely fused sulcus medianus, in early intrauterine life. The possibility of cytomegalic etiology of the malformation is discussed. However the occurrence of viral disease in a previous abnormal brain cannot be discarded. The cystic symmetrical encephalopathy is explained through a redistribution (shunting) of the cerebral blood flow, brought about by the existence of a peculiar mechanism which he calls - priority blood supplying system. This proposed system probably acts independently of the cerebral blood flow autoregulatory mechanisms in emergency states, shunting the blood to the vitaly more important homeostatic neurovegetative centers. This mechanism, in spite of its actual effectiveness, if prolonged, may be deleterious to the excluded territories and produce irreversible damages. The morphologic expression of these damages are the multiple symmetrical brain infarctions. Following occasional survival, the tissue debris of the destroyed structures in the involved areas, are slowly and progressively removed by reabsorption and replaced by unusual symmetrical cavitations.", "contents": "[Cytomegaly and central nervous system abnormalities. Report of 2 cases associated with agenesia of the corpus callosum and cystic encephalopathy]. Two cases of cytomegaly of the central nervous system of infants, disclosing typical viral inclusions in the brain tissues, associated with agenesia of the corpus callosum and cystic symmetrical post-infarction encephalopathy are reported. It is suggested that the callosal defect was caused by cystic degeneration occuring within the lamina reuniens and the prematurely fused sulcus medianus, in early intrauterine life. The possibility of cytomegalic etiology of the malformation is discussed. However the occurrence of viral disease in a previous abnormal brain cannot be discarded. The cystic symmetrical encephalopathy is explained through a redistribution (shunting) of the cerebral blood flow, brought about by the existence of a peculiar mechanism which he calls - priority blood supplying system. This proposed system probably acts independently of the cerebral blood flow autoregulatory mechanisms in emergency states, shunting the blood to the vitaly more important homeostatic neurovegetative centers. This mechanism, in spite of its actual effectiveness, if prolonged, may be deleterious to the excluded territories and produce irreversible damages. The morphologic expression of these damages are the multiple symmetrical brain infarctions. Following occasional survival, the tissue debris of the destroyed structures in the involved areas, are slowly and progressively removed by reabsorption and replaced by unusual symmetrical cavitations."} {"id": "PMID:169765", "title": "Adrenoleukodystrophy. A clinical and pathological study of 17 cases.", "content": "Adrenoleukodystrophy was diagnosed pathologically in 17 male patients. The diagnosis was suggested by clinical and laboratory signs of primary adrenal failure and by neurological signs referable to the degeneration of white matter. Neurological findings usually predominated over clinical stigmata of adrenal failure. Adrenal biopsy has proved to be the most reliable diagnostic test, while brain biopsy has often been misleading. The histological picture of the brain lesion differs substantially from that of the adrenal, but the presence of similar ultrastructural cytoplasmic inclusions suggests a common metabolic disorder. Morphological analysis of the cerebral lesion indicates that the destruction may spread in a caudal-rostral direction. The intense inflammatory cell response occurs within the demyelinated areas, behing the area of active myelin breakdown, and appears to be a secondary feature of white matter degeneration.", "contents": "Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Adrenoleukodystrophy was diagnosed pathologically in 17 male patients. The diagnosis was suggested by clinical and laboratory signs of primary adrenal failure and by neurological signs referable to the degeneration of white matter. Neurological findings usually predominated over clinical stigmata of adrenal failure. Adrenal biopsy has proved to be the most reliable diagnostic test, while brain biopsy has often been misleading. The histological picture of the brain lesion differs substantially from that of the adrenal, but the presence of similar ultrastructural cytoplasmic inclusions suggests a common metabolic disorder. Morphological analysis of the cerebral lesion indicates that the destruction may spread in a caudal-rostral direction. The intense inflammatory cell response occurs within the demyelinated areas, behing the area of active myelin breakdown, and appears to be a secondary feature of white matter degeneration."} {"id": "PMID:169766", "title": "APO low density lipoprotein localization. Intracranial and extracranial atherosclerotic lesions from human normolipoproteinemics and hyperlipoproteinemics.", "content": "APO low density lipoprotein (apoB), the major protein in plasma low (LDL) and very low (VLDL) density lipoproteins, was localized in extracranial and intracranial arteries from normolipoproteinemics and hyperlipoproteinemics to determine if apoB extensiveness and localization varied with plasma lipoprotein profile. Specimens of carotid bifureation, internal carotid, basilar, and middle cerebral arteries from 23 subjects with normal lipoprotein levels, four with elevated LDL (type II), and 13 with elevated VLDL (type IV) values were studied with the employment of immunofluorescence techniques. Although the apoB localization pattern was identical in each group, extensiveness of positive localization was greatest in lesions from type II cases and the same in lesions from type IV and normolipoproteinemics. This suggests that sites of apoB retention are dependent on the chemical and structural changes in atherosclerotic arteries, whereas extensiveness correlates with the apoB concentration gradient between plasma and tissue.", "contents": "APO low density lipoprotein localization. Intracranial and extracranial atherosclerotic lesions from human normolipoproteinemics and hyperlipoproteinemics. APO low density lipoprotein (apoB), the major protein in plasma low (LDL) and very low (VLDL) density lipoproteins, was localized in extracranial and intracranial arteries from normolipoproteinemics and hyperlipoproteinemics to determine if apoB extensiveness and localization varied with plasma lipoprotein profile. Specimens of carotid bifureation, internal carotid, basilar, and middle cerebral arteries from 23 subjects with normal lipoprotein levels, four with elevated LDL (type II), and 13 with elevated VLDL (type IV) values were studied with the employment of immunofluorescence techniques. Although the apoB localization pattern was identical in each group, extensiveness of positive localization was greatest in lesions from type II cases and the same in lesions from type IV and normolipoproteinemics. This suggests that sites of apoB retention are dependent on the chemical and structural changes in atherosclerotic arteries, whereas extensiveness correlates with the apoB concentration gradient between plasma and tissue."} {"id": "PMID:169767", "title": "Reye's syndrome and cerebellar intracytoplasmic inclusion bodies.", "content": "A patient with Reye syndrome had intracytoplasmic inclusion bodies in Purkinje cells. Electron microscopical examination demonstrated the inclusions to contain internal particles, but these were not identifiable as known virions. Results of viral studies were normal.", "contents": "Reye's syndrome and cerebellar intracytoplasmic inclusion bodies. A patient with Reye syndrome had intracytoplasmic inclusion bodies in Purkinje cells. Electron microscopical examination demonstrated the inclusions to contain internal particles, but these were not identifiable as known virions. Results of viral studies were normal."} {"id": "PMID:169768", "title": "Acute SSPE.", "content": "Two patients had acute fulminanting encephalitis and the typical pathological changes of subacute slcerosing panencephalitis (SSPE). It is suggested that SSPE should be considered in the differential diagnosis of acute viral encephalitis.", "contents": "Acute SSPE. Two patients had acute fulminanting encephalitis and the typical pathological changes of subacute slcerosing panencephalitis (SSPE). It is suggested that SSPE should be considered in the differential diagnosis of acute viral encephalitis."} {"id": "PMID:169770", "title": "Synovial sarcoma of the laryngopharynx.", "content": "Synovial sarcoma of the laryngopharynx is an extremely rare neoplasm. To date, only two such cases have been reported. We describe two additional patients in whom this lesion occurred as a primary neoplasm of the laryngopharynx. Hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. The difficulties that may be encountered in histologic diagnosis are emphasized. Our findings suggest that an aggressive surgical approach is indicated. Adjuvant therapy with irradiation and the chemotherapeutic agent, doxorubicin (Adriamycin), may contribute to better survival rates.", "contents": "Synovial sarcoma of the laryngopharynx. Synovial sarcoma of the laryngopharynx is an extremely rare neoplasm. To date, only two such cases have been reported. We describe two additional patients in whom this lesion occurred as a primary neoplasm of the laryngopharynx. Hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. The difficulties that may be encountered in histologic diagnosis are emphasized. Our findings suggest that an aggressive surgical approach is indicated. Adjuvant therapy with irradiation and the chemotherapeutic agent, doxorubicin (Adriamycin), may contribute to better survival rates."} {"id": "PMID:169771", "title": "Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction.", "content": "In 1961, Hallowell Davis proposed the occurrence of the following general sequence of interrelated events in sense organs, in response to specific sensory inputs: (1) the generation of receptor potentials in the sensory cells; (2) chemical transmission across the synapses between hair cells and afferent dendrites; and (3) the triggering of postsynaptic generator potentials capable of eliciting the actual nerve action potentials. Although at the time of his writing there was no evidence for this hypothesis in the auditory organ, there is now good support for the occurrence of all three events and for their general importance in the sensory transduction process.", "contents": "Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction. In 1961, Hallowell Davis proposed the occurrence of the following general sequence of interrelated events in sense organs, in response to specific sensory inputs: (1) the generation of receptor potentials in the sensory cells; (2) chemical transmission across the synapses between hair cells and afferent dendrites; and (3) the triggering of postsynaptic generator potentials capable of eliciting the actual nerve action potentials. Although at the time of his writing there was no evidence for this hypothesis in the auditory organ, there is now good support for the occurrence of all three events and for their general importance in the sensory transduction process."} {"id": "PMID:169772", "title": "Epstein-Barr virus associated with episodes of recurrent tonsillitis.", "content": "A group of patients with a history of recurrent tonsillitis were observed during an acute episode to determine the cause of the infection. The microbial pathogen that was consistently implicated was the Epstein-Barr virus. Seventeen (65%) of 26 patients exhibited a substantial seroconversion to the early antigen of Epstein-Barr-virus-infected lymphoblastoid cells (P3HR-1). We conclude that there is a high incidence of tonsillitis associated with the Epstein-Barr virus. The propensity of the virus for the palatine tonsils, a rich source of B cells, in suggested. Furthermore, the value of monitoring early antigen titers to confirm the nature of the infection is apparent, bearing relevance to future studies of this virus.", "contents": "Epstein-Barr virus associated with episodes of recurrent tonsillitis. A group of patients with a history of recurrent tonsillitis were observed during an acute episode to determine the cause of the infection. The microbial pathogen that was consistently implicated was the Epstein-Barr virus. Seventeen (65%) of 26 patients exhibited a substantial seroconversion to the early antigen of Epstein-Barr-virus-infected lymphoblastoid cells (P3HR-1). We conclude that there is a high incidence of tonsillitis associated with the Epstein-Barr virus. The propensity of the virus for the palatine tonsils, a rich source of B cells, in suggested. Furthermore, the value of monitoring early antigen titers to confirm the nature of the infection is apparent, bearing relevance to future studies of this virus."} {"id": "PMID:169773", "title": "Temporal bone findings in cryptococcal meningitis.", "content": "A 19-year-old woman with cryptococcal meningitis died as a result of her disease, in spite of both intravenous and intraventricular administration of amphotericin B. Gross and microscopic examinations revealed multiple cysts containing Cryptococcus neoformans within the central nervous system. Studies of the temporal bones revealed both neural and end organ destruction with the presence of Cryptococcus when stained by Gomori methenamine silver nitrate method. We present the results of audiometric and vestibular examinations. The case history depicts a progressive neurological involvement by Cryptococcus.", "contents": "Temporal bone findings in cryptococcal meningitis. A 19-year-old woman with cryptococcal meningitis died as a result of her disease, in spite of both intravenous and intraventricular administration of amphotericin B. Gross and microscopic examinations revealed multiple cysts containing Cryptococcus neoformans within the central nervous system. Studies of the temporal bones revealed both neural and end organ destruction with the presence of Cryptococcus when stained by Gomori methenamine silver nitrate method. We present the results of audiometric and vestibular examinations. The case history depicts a progressive neurological involvement by Cryptococcus."} {"id": "PMID:169774", "title": "Pulmonary interstitial fibrosis from paraquat in the hamster.", "content": "The effects of paraquat in hamsters were evaluated to find a rodent model of interstitial pulmonary disease free from spontaneous infection. Because the repeated doses necessary to produce chronic lung injury suggested hypersensitivity mechanisms, concurrently administered Freund adjuvant and adenocorticotrophic hormone (ACTH) were tested separately. Effects were measured by mortality, change in body weight, and morphometric estimate of lung injury. Findings were as follows: (1) only repeated doses in a very narrow range produced chronic interstitial injury; (2) ACTH clearly protected animals from the general systemic and pulmonary effects of paraquat; and (3) adjuvant specifically protected against the pulmonary injury alone. There was no evidence of immunologic contribution to paraquat injury.", "contents": "Pulmonary interstitial fibrosis from paraquat in the hamster. The effects of paraquat in hamsters were evaluated to find a rodent model of interstitial pulmonary disease free from spontaneous infection. Because the repeated doses necessary to produce chronic lung injury suggested hypersensitivity mechanisms, concurrently administered Freund adjuvant and adenocorticotrophic hormone (ACTH) were tested separately. Effects were measured by mortality, change in body weight, and morphometric estimate of lung injury. Findings were as follows: (1) only repeated doses in a very narrow range produced chronic interstitial injury; (2) ACTH clearly protected animals from the general systemic and pulmonary effects of paraquat; and (3) adjuvant specifically protected against the pulmonary injury alone. There was no evidence of immunologic contribution to paraquat injury."} {"id": "PMID:169775", "title": "The effects of additives on the thermal behaviour of gypsum-bonded casting investments. Part I.", "content": "In the formulation of gypsum-bonded casting investments, small amounts of certain modifiers are sometimes added to increase the investment's thermal expansion. In the present investigation, a systematic study has been made of the effects on thermal expansion of adding boric acid and sodium chloride to the investment powder, and glycerol to the mixing water. The combination of 0.2 per cent of sodium chloride in the powder, and 10 per cent of glycerol in the mixing water, appears to offer most promise in the formulation of an investment with a high thermal expansion.", "contents": "The effects of additives on the thermal behaviour of gypsum-bonded casting investments. Part I. In the formulation of gypsum-bonded casting investments, small amounts of certain modifiers are sometimes added to increase the investment's thermal expansion. In the present investigation, a systematic study has been made of the effects on thermal expansion of adding boric acid and sodium chloride to the investment powder, and glycerol to the mixing water. The combination of 0.2 per cent of sodium chloride in the powder, and 10 per cent of glycerol in the mixing water, appears to offer most promise in the formulation of an investment with a high thermal expansion."} {"id": "PMID:169776", "title": "The sterilization of gutta-percha points.", "content": "The traditional methods employed for the sterilization of gutta-percha points are unsatisfactory. The use of propylene oxide for this purpose is described and experimental evidence is advanced to support this use.", "contents": "The sterilization of gutta-percha points. The traditional methods employed for the sterilization of gutta-percha points are unsatisfactory. The use of propylene oxide for this purpose is described and experimental evidence is advanced to support this use."} {"id": "PMID:169777", "title": "Urinary cyclic AMP in diagnosis and management of hypercalcaemia: studies of patients without primary hyperparathyroidism.", "content": "Urinary adenosine -3' ,5' - cyclic monophosphate was measured in 14 patients with hypercalcaemia not caused by primary hyperparathyroidism. Increased levels were found in patients with malignant disease without bone metastases and believed to be examples of paraendocrine syndrome. Decreased levels were found in patients with metastatic carcinoma involving bone, and in patients with multiple myeloma, lymphoma and immobilisation after fracture. Results obtained during treatment for hypercalaemia are described in three patients. In two hypercalcaemic patients (one with hyperthyroidism and one with breast cancer with bone metastases) normal levels were found. This measurement is a useful substitute for assay of serum parathyroid hormone and is of value in the diagnosis of hypercalcaemia, in monitoring effects of treatment and in revealing underlying mechanisms.", "contents": "Urinary cyclic AMP in diagnosis and management of hypercalcaemia: studies of patients without primary hyperparathyroidism. Urinary adenosine -3' ,5' - cyclic monophosphate was measured in 14 patients with hypercalcaemia not caused by primary hyperparathyroidism. Increased levels were found in patients with malignant disease without bone metastases and believed to be examples of paraendocrine syndrome. Decreased levels were found in patients with metastatic carcinoma involving bone, and in patients with multiple myeloma, lymphoma and immobilisation after fracture. Results obtained during treatment for hypercalaemia are described in three patients. In two hypercalcaemic patients (one with hyperthyroidism and one with breast cancer with bone metastases) normal levels were found. This measurement is a useful substitute for assay of serum parathyroid hormone and is of value in the diagnosis of hypercalcaemia, in monitoring effects of treatment and in revealing underlying mechanisms."} {"id": "PMID:169778", "title": "Urinary excretion of cyclic AMP in primary hyperparathyroidism.", "content": "Urinary adenosine 3' 5' - cyclic monophosphate (cyclic AMP) was assessed by a competitive protein binding method in 19 patients with primary hyperparathyroidism (PHPT) and in 15 control subjects. The mean value of 6.6 +/- S.E. 0-64 muM per 24 hours for the patients with PHPT was higher (P less than 0-001) than the mean control value of 3-2 +/- 0-24 muM per 24 hours. In all hypercalcaemic patients without renal insufficiency, urinary cyclic AMP excretion was more than 4 muM per 24 hours and decreased in the 15 patients investigated after parathyroidectomy. In a normocalcaemic hyperparathyroid patient and in three hyperparathyroid patients with renal insufficiency, urinary cyclic AMP was less than 4 muM per 24 hours.", "contents": "Urinary excretion of cyclic AMP in primary hyperparathyroidism. Urinary adenosine 3' 5' - cyclic monophosphate (cyclic AMP) was assessed by a competitive protein binding method in 19 patients with primary hyperparathyroidism (PHPT) and in 15 control subjects. The mean value of 6.6 +/- S.E. 0-64 muM per 24 hours for the patients with PHPT was higher (P less than 0-001) than the mean control value of 3-2 +/- 0-24 muM per 24 hours. In all hypercalcaemic patients without renal insufficiency, urinary cyclic AMP excretion was more than 4 muM per 24 hours and decreased in the 15 patients investigated after parathyroidectomy. In a normocalcaemic hyperparathyroid patient and in three hyperparathyroid patients with renal insufficiency, urinary cyclic AMP was less than 4 muM per 24 hours."} {"id": "PMID:169779", "title": "Type V hyperlipoproteinaemia re-visted: findings in a sydney population.", "content": "The clinical and biochemical features of eleven patients with Type V hyperlipoproteinaemia have been reviewed. All patients were male, and there was a high incidence in the group of obesity, vascular disease, acute abdominal pain, gout, diabetes mellitus and alcoholism. Plasma cholesterol concentrations ranged from 212 to 1512 mg/100ml and triglycerides from 708 to 7670 mg/100 ml. Lipaemia was associated with significant hyponatraemia, and also interfered with the determination of plasma glucose and serum amylase. Chylomicronaemia and hyperprebetalipoproteinaemia were accompanied by reduction in the pools of beta and alpha lipoproteins. All lipoprotein classes were relatively depleted of cholesterol compared to triglyceride. There was a variable pattern of treatment response. In some patients alcohol withdrawal produced a rapid improvement in plasma lipids. In diabetes mellitus there were two types of response: a rapid one in chronic insulin deficiency, and secondly, a more gradual one in mild diabetes associated with hyperinsulinaemia. In other patients there was a rapid response to carbohydrate-calorie restriction but the respective contributions of each of the steps remained unclear.", "contents": "Type V hyperlipoproteinaemia re-visted: findings in a sydney population. The clinical and biochemical features of eleven patients with Type V hyperlipoproteinaemia have been reviewed. All patients were male, and there was a high incidence in the group of obesity, vascular disease, acute abdominal pain, gout, diabetes mellitus and alcoholism. Plasma cholesterol concentrations ranged from 212 to 1512 mg/100ml and triglycerides from 708 to 7670 mg/100 ml. Lipaemia was associated with significant hyponatraemia, and also interfered with the determination of plasma glucose and serum amylase. Chylomicronaemia and hyperprebetalipoproteinaemia were accompanied by reduction in the pools of beta and alpha lipoproteins. All lipoprotein classes were relatively depleted of cholesterol compared to triglyceride. There was a variable pattern of treatment response. In some patients alcohol withdrawal produced a rapid improvement in plasma lipids. In diabetes mellitus there were two types of response: a rapid one in chronic insulin deficiency, and secondly, a more gradual one in mild diabetes associated with hyperinsulinaemia. In other patients there was a rapid response to carbohydrate-calorie restriction but the respective contributions of each of the steps remained unclear."} {"id": "PMID:169780", "title": "Hepatitis B antigen and auto-antibodies in chronic liver diseases in Hong Kong.", "content": "The frequency of occurrence of hepatitis B antigen (HBAg) and certain tissue autoantibodies [antinuclear antibody (ANA), smooth muscle antibody (SMA) and mitochondrial antibody (MIA)] were studied with the microtiter complement fixation and immunofluorescence techniques respectively in a group of patients suffering from chronic liver diseases. These were chronic hepatitis (30), cirrhosis of the liver (66) and hepatocellular carcinoma, mostly with underlying cirrhosis (100). A group of closely matched hospital in-patients served as controls. HBAg was found in high frequency in the patients with liver disease (60% in chronic hepatitis, 36.4% in cirrhosis and 49% in hepatocellular carcinoma) whereas tissue auto-antibodies were found in lower frequencies (16.7%, 10.6% and 13% in the three groups respectively). However, in both the frequency was significantly higher than that in the controls (9.2% for HBAg and 0.8% for auto-antibodies). There was a negative correlation between HBAg and tissue auto-antibodies in the group of patients with liver disease when taken as a whole (x2=14.3, P less than 0.001). These results suggest a possible aetiological role played by hepatitis virus B in hepatocellular carcinoma through chronic hepatitis and cirrhosis in Hong Kong while the mutual exclusion between HBAg and auto-antibodies supports the hypothesis of heterogeneity in the aetiology of chronic liver diseases. The patients with auto-antibodies may belong to the auto-immune category but no definate conclusion can be reached until the role played by hepatitis virus A in chronic liver diseases is clarified when more reliable techniques for its identification are available.", "contents": "Hepatitis B antigen and auto-antibodies in chronic liver diseases in Hong Kong. The frequency of occurrence of hepatitis B antigen (HBAg) and certain tissue autoantibodies [antinuclear antibody (ANA), smooth muscle antibody (SMA) and mitochondrial antibody (MIA)] were studied with the microtiter complement fixation and immunofluorescence techniques respectively in a group of patients suffering from chronic liver diseases. These were chronic hepatitis (30), cirrhosis of the liver (66) and hepatocellular carcinoma, mostly with underlying cirrhosis (100). A group of closely matched hospital in-patients served as controls. HBAg was found in high frequency in the patients with liver disease (60% in chronic hepatitis, 36.4% in cirrhosis and 49% in hepatocellular carcinoma) whereas tissue auto-antibodies were found in lower frequencies (16.7%, 10.6% and 13% in the three groups respectively). However, in both the frequency was significantly higher than that in the controls (9.2% for HBAg and 0.8% for auto-antibodies). There was a negative correlation between HBAg and tissue auto-antibodies in the group of patients with liver disease when taken as a whole (x2=14.3, P less than 0.001). These results suggest a possible aetiological role played by hepatitis virus B in hepatocellular carcinoma through chronic hepatitis and cirrhosis in Hong Kong while the mutual exclusion between HBAg and auto-antibodies supports the hypothesis of heterogeneity in the aetiology of chronic liver diseases. The patients with auto-antibodies may belong to the auto-immune category but no definate conclusion can be reached until the role played by hepatitis virus A in chronic liver diseases is clarified when more reliable techniques for its identification are available."} {"id": "PMID:169781", "title": "Inappropiate ADH secretion associated with massive vincristine overdosage.", "content": "A patient with acute lymphocytic leukemia is described who developed meningeal leukemia 14 months after the initial diagnosis was made. As part of his antileukemic therapy, at that time, he received prednisone and vincristine, given prophylactically to maintain a bone marrow remission. He inadvertently received 15 mg of vincristine instead of 1.5 mg. Following this overdosage he developed pancytopaenia, mild neurotoxicity and subsequently a grand mal seizure associated with the delayed onset of hyponatremia. This was presumed to be due to the inappropriate secretion of antidiuretic hormone (ADH) secondary to vincristine toxicity. This responded to fluid restriction and anti-epileptiform therapy.", "contents": "Inappropiate ADH secretion associated with massive vincristine overdosage. A patient with acute lymphocytic leukemia is described who developed meningeal leukemia 14 months after the initial diagnosis was made. As part of his antileukemic therapy, at that time, he received prednisone and vincristine, given prophylactically to maintain a bone marrow remission. He inadvertently received 15 mg of vincristine instead of 1.5 mg. Following this overdosage he developed pancytopaenia, mild neurotoxicity and subsequently a grand mal seizure associated with the delayed onset of hyponatremia. This was presumed to be due to the inappropriate secretion of antidiuretic hormone (ADH) secondary to vincristine toxicity. This responded to fluid restriction and anti-epileptiform therapy."} {"id": "PMID:169782", "title": "Ectopic adrenocorticotrophic hormone production and neoplasm.", "content": "Three patients presented with severe hypokalaemic, hypochloraemic alkalosis, muscle weakness and later cutaneoud pigmentation. There were few signs of Cushing's syndrome. Two had bronchial and one pancreatic neoplasm. Plasma cortisol and urinary steroid metabolites were extremely elevated and synacthen stimulation showed significant adrenal capacity even with adrenal metastases. Aminoglutethamide reduced plasma cortisol in two patients.", "contents": "Ectopic adrenocorticotrophic hormone production and neoplasm. Three patients presented with severe hypokalaemic, hypochloraemic alkalosis, muscle weakness and later cutaneoud pigmentation. There were few signs of Cushing's syndrome. Two had bronchial and one pancreatic neoplasm. Plasma cortisol and urinary steroid metabolites were extremely elevated and synacthen stimulation showed significant adrenal capacity even with adrenal metastases. Aminoglutethamide reduced plasma cortisol in two patients."} {"id": "PMID:169784", "title": "Inheritance of a lethal immunodeficiency disease of Arabian foals.", "content": "A fatal syndrome of certain Arabian foals which begins at about 25 days of age (range 14 to 46 days) and which runs a course of about 23 days (range 13 to 42 days) is described. The syndrome, which affected 17 foals on a single farm is further characterised by pneumonia, in some instances by dermatitis (dermatophilosis) and other infections, together with a progressive decline in health till death at about 49 days of age (range 34 to 77 days), despite intensive therapy. Four of the foals, on histopathological evidence, had adenviral pneumonia, in 2 foals there was histopathological evidence of an immunodeficiency disease and an adenovirus was isolated from 1 foal. It is argued, however, that the 17 foals were affected by a single, specific syndrome (an immunodeficiency disease) and that this disease is inherited as a simple, recessive, autosomal gene.", "contents": "Inheritance of a lethal immunodeficiency disease of Arabian foals. A fatal syndrome of certain Arabian foals which begins at about 25 days of age (range 14 to 46 days) and which runs a course of about 23 days (range 13 to 42 days) is described. The syndrome, which affected 17 foals on a single farm is further characterised by pneumonia, in some instances by dermatitis (dermatophilosis) and other infections, together with a progressive decline in health till death at about 49 days of age (range 34 to 77 days), despite intensive therapy. Four of the foals, on histopathological evidence, had adenviral pneumonia, in 2 foals there was histopathological evidence of an immunodeficiency disease and an adenovirus was isolated from 1 foal. It is argued, however, that the 17 foals were affected by a single, specific syndrome (an immunodeficiency disease) and that this disease is inherited as a simple, recessive, autosomal gene."} {"id": "PMID:169785", "title": "Bluetongue in sheep and goats.", "content": "A description is given of the symptomatology, pathology and pathogenesis of bluetongue in sheep and goats. The economic significance of the disease in South Africa is discussed.", "contents": "Bluetongue in sheep and goats. A description is given of the symptomatology, pathology and pathogenesis of bluetongue in sheep and goats. The economic significance of the disease in South Africa is discussed."} {"id": "PMID:169786", "title": "Bluetongue: the disease in cattle.", "content": "Most researchers in South Africa found that although BT virus could be isolated from apparently healthy cattle and from inoculated cattle the virus did not produce overt clinical disease in cattle. However, when epizootics were reported outside Africa, clinical signs were observed in cattle in Israel, Palestine, Syria, Portugal, and Spain. Most natural BT infections in cattle in the United States do not result in overt clinical signs. However, in certain infected herds, approximately 5% of the cattle show from mild to severe disease. Except for severe cases, spontaneous recovery is usual. The clinical diagnosis of BT in cattle is difficult and requires laboratory assistance. Culicoides variipennis can serve as a vector of BT virus from cattle to cattle, cattle to sheep, sheep to cattle, and sheep to sheep. In utero transmission occurs in cattle and can result in abortion, hydraencephaly, congenital deformity, and birth of viraemic calves which may or may not develop BT antibody. Calves inoculated in utero or those born to infected dams may have a persistent viraemia with or without BT antibody. tone such animal has been held in insect-secure quarters and has continued to harbour virus for 3 years. Bluetongue virus was isolated from the semen of experimentally infected bulls. Calves inoculated with BT virus and also given an immuno-suppressant developed marked clinical disease in 8 to 12 days. Bluetongue virus is very closely associated with the erythrocytes of infected cattle, sheep, and goats. Cattle are considered important and relatively long-term virus reservoirs. In attempts to determine the maximum period of viraemia in cattle it is necessary to inoculate washed erythrocytes, rather than whole blood, and to use susceptible sheep as the assay system rather than embryonated chicken eggs.", "contents": "Bluetongue: the disease in cattle. Most researchers in South Africa found that although BT virus could be isolated from apparently healthy cattle and from inoculated cattle the virus did not produce overt clinical disease in cattle. However, when epizootics were reported outside Africa, clinical signs were observed in cattle in Israel, Palestine, Syria, Portugal, and Spain. Most natural BT infections in cattle in the United States do not result in overt clinical signs. However, in certain infected herds, approximately 5% of the cattle show from mild to severe disease. Except for severe cases, spontaneous recovery is usual. The clinical diagnosis of BT in cattle is difficult and requires laboratory assistance. Culicoides variipennis can serve as a vector of BT virus from cattle to cattle, cattle to sheep, sheep to cattle, and sheep to sheep. In utero transmission occurs in cattle and can result in abortion, hydraencephaly, congenital deformity, and birth of viraemic calves which may or may not develop BT antibody. Calves inoculated in utero or those born to infected dams may have a persistent viraemia with or without BT antibody. tone such animal has been held in insect-secure quarters and has continued to harbour virus for 3 years. Bluetongue virus was isolated from the semen of experimentally infected bulls. Calves inoculated with BT virus and also given an immuno-suppressant developed marked clinical disease in 8 to 12 days. Bluetongue virus is very closely associated with the erythrocytes of infected cattle, sheep, and goats. Cattle are considered important and relatively long-term virus reservoirs. In attempts to determine the maximum period of viraemia in cattle it is necessary to inoculate washed erythrocytes, rather than whole blood, and to use susceptible sheep as the assay system rather than embryonated chicken eggs."} {"id": "PMID:169787", "title": "Bluetongue-like disease of deer.", "content": "A comparison has been made of the disease produced in white-tailed deer by the viruses of epizootic haemorrhagic disease and bluetongue. The similar nature of these diseases in deer and of some of the viral properties has been described. Although these two viruses are considered to be distinct, it is possible by employing an unnatural procedure to produce antibody which will demonstrate a minor antigenic component common to both viruses. Biological features that differ between the two viruses have also been noted.", "contents": "Bluetongue-like disease of deer. A comparison has been made of the disease produced in white-tailed deer by the viruses of epizootic haemorrhagic disease and bluetongue. The similar nature of these diseases in deer and of some of the viral properties has been described. Although these two viruses are considered to be distinct, it is possible by employing an unnatural procedure to produce antibody which will demonstrate a minor antigenic component common to both viruses. Biological features that differ between the two viruses have also been noted."} {"id": "PMID:169788", "title": "Ibaraki disease and its relationship to bluetongue.", "content": "Ibaraki disease, an epizootic disease of cattle in Japan resembling bluetongue, is characterized by fever and lesions affecting the mucous membranes, the skin, the musculature and vascular system. Degeneration of striated muscular tissue is observed in the oesophagus, larynx, pharynx, tongue and the skeletal muscles. Oedema and haemorrhage are marked in the mouth, lips, abomasum, around the coronets, etc., and are occasionally followed by degeneration of the epithelium leading to erosions or ulcerations. Severe lesions affecting the oesophageal and laryngopharyngeal musculature cause difficulty in swallowing which in turn produces dehydration and emaciation, and occasionally the aspiration pneumonia, which constitute the major causes of death of affected animals. These clinical and pathological findings indicate the similarity of the disease to bluetongue in sheep and cattle. Ibaraki disease was first recognised in Japan in 1959 and 1960. Seasonally its occurrence is limited to late summer and autumn, and geographically to the central and western parts of Japan, roughly south of 37 degrees north latitude. It is absent from the higher altitudes. The seasonal and geographical incidence suggests the possibility of an arthropod vector; but direct evidence for such a vector is still lacking. Serological data suggest the presence of Ibaraki virus on Bali Island in Indonesia and in Taiwan. The disease can be transmitted serially in calves by the intravenous inoculation of blood obtained at the height of a febrile reaction. Ibaraki virus can be isolated in bovine cell cultures from both natural and experimentally produced cases of the disease. The virus multiplies and induces cytopathic effects in primary cultures of bovine, sheep and hamster lung origin, and L cells; but it does not grow in primary cultures of horse and swine kidney nor in HeLa cell cultures. The virus is readily passaged serially in 4 to 5-day-old eggs by yolk-sac inoculation and incubation at 33.5 degrees C. It multiplies in the brains of mice of any age after incracerebral inoculation but younger mice give a better viral growth and develop encephalitis. No evidence has been obtained that rabbits and guinea pigs are susceptible to Ibaraki virus...", "contents": "Ibaraki disease and its relationship to bluetongue. Ibaraki disease, an epizootic disease of cattle in Japan resembling bluetongue, is characterized by fever and lesions affecting the mucous membranes, the skin, the musculature and vascular system. Degeneration of striated muscular tissue is observed in the oesophagus, larynx, pharynx, tongue and the skeletal muscles. Oedema and haemorrhage are marked in the mouth, lips, abomasum, around the coronets, etc., and are occasionally followed by degeneration of the epithelium leading to erosions or ulcerations. Severe lesions affecting the oesophageal and laryngopharyngeal musculature cause difficulty in swallowing which in turn produces dehydration and emaciation, and occasionally the aspiration pneumonia, which constitute the major causes of death of affected animals. These clinical and pathological findings indicate the similarity of the disease to bluetongue in sheep and cattle. Ibaraki disease was first recognised in Japan in 1959 and 1960. Seasonally its occurrence is limited to late summer and autumn, and geographically to the central and western parts of Japan, roughly south of 37 degrees north latitude. It is absent from the higher altitudes. The seasonal and geographical incidence suggests the possibility of an arthropod vector; but direct evidence for such a vector is still lacking. Serological data suggest the presence of Ibaraki virus on Bali Island in Indonesia and in Taiwan. The disease can be transmitted serially in calves by the intravenous inoculation of blood obtained at the height of a febrile reaction. Ibaraki virus can be isolated in bovine cell cultures from both natural and experimentally produced cases of the disease. The virus multiplies and induces cytopathic effects in primary cultures of bovine, sheep and hamster lung origin, and L cells; but it does not grow in primary cultures of horse and swine kidney nor in HeLa cell cultures. The virus is readily passaged serially in 4 to 5-day-old eggs by yolk-sac inoculation and incubation at 33.5 degrees C. It multiplies in the brains of mice of any age after incracerebral inoculation but younger mice give a better viral growth and develop encephalitis. No evidence has been obtained that rabbits and guinea pigs are susceptible to Ibaraki virus..."} {"id": "PMID:169789", "title": "Serological methods in the diagnosis of bluetongue.", "content": "The viral antibodies in the serum of cattle, sheep and deer are not detectable in the ordinary direct CF test. We have shown that the so-called \"non complement-fixing\" viral antibodies in the serum of these animal species can be demonstrated by the MDCF test. The MDCF test, as well as the micro AGP test, are group reactive, with all BT isolates studied. However, it is possible with these tests to differentiate antigenically BT virus from EHD virus. The FAT was also useful in differentiating BT virus grown in TC cells from the EHD virus. In the PRN test, all the BT virus isolates studied cross reacted and although quantitative differences were frequently observed, no obvious antigenic classification was possible with the antiserums used in this work. Reactions between the BT viral isolates and the EHD virus were all within the limits of what is presently considered to be non-specific inhibition.", "contents": "Serological methods in the diagnosis of bluetongue. The viral antibodies in the serum of cattle, sheep and deer are not detectable in the ordinary direct CF test. We have shown that the so-called \"non complement-fixing\" viral antibodies in the serum of these animal species can be demonstrated by the MDCF test. The MDCF test, as well as the micro AGP test, are group reactive, with all BT isolates studied. However, it is possible with these tests to differentiate antigenically BT virus from EHD virus. The FAT was also useful in differentiating BT virus grown in TC cells from the EHD virus. In the PRN test, all the BT virus isolates studied cross reacted and although quantitative differences were frequently observed, no obvious antigenic classification was possible with the antiserums used in this work. Reactions between the BT viral isolates and the EHD virus were all within the limits of what is presently considered to be non-specific inhibition."} {"id": "PMID:169790", "title": "The comparative sensitivity of sheep and chicken embryos to bluetongue virus and observations on viraemia in experimentally infected sheep.", "content": "The virus titre in sheep blood samples received from BT-suspected cases in the field was assayed in sheep and in chicken embryos. These infected blood samples represented 3 different BT virus types: 4, 10 and 16. Three identical experiments were performed, one with each of the 3 different virus types. Ten-fold dilutions of the infected blood samples were prepared and 1 ml of each blood dilution was inoculated IV into series of 10 to 12-month old susceptible sheep; at the same time 0.1 ml of each dilution was inoculated IV into series of 10 to 13-day-old chicken embryos. The virus titre was found to be similar when assayed in the two host systems. There was no correlation between the amount of virus inoculated and the severity of symptoms in the inoculated sheep. The virus content in daily blood samples collected from the experimental sheep was assayed by IV inoculation of CE. Virus was isolated from all the reacting sheep and was detected sometimes as early as 1 day PI and as late as 30 days PI. A high titre of log10 4.0 to 7.0 per 1 ml of blood was recorded during several consecutive days before and after the onset of clinical signs. There seemed to be an inverse ratio between the amount of virus inoculated and the number of days the virus persisted in the bloodstream. The neutralisation index in day 22 serum samples was 3.5 to 4.5. Virus was isolated from some of the reacting sheep on the day that these antibody levels were recorded. Since the comparative simultaneous titrations of BT virus in sheep and in CE yielded similar results, the IV inoculation of CE is advocated as the routine method to be employed for laboratory diagnosis of this disease.", "contents": "The comparative sensitivity of sheep and chicken embryos to bluetongue virus and observations on viraemia in experimentally infected sheep. The virus titre in sheep blood samples received from BT-suspected cases in the field was assayed in sheep and in chicken embryos. These infected blood samples represented 3 different BT virus types: 4, 10 and 16. Three identical experiments were performed, one with each of the 3 different virus types. Ten-fold dilutions of the infected blood samples were prepared and 1 ml of each blood dilution was inoculated IV into series of 10 to 12-month old susceptible sheep; at the same time 0.1 ml of each dilution was inoculated IV into series of 10 to 13-day-old chicken embryos. The virus titre was found to be similar when assayed in the two host systems. There was no correlation between the amount of virus inoculated and the severity of symptoms in the inoculated sheep. The virus content in daily blood samples collected from the experimental sheep was assayed by IV inoculation of CE. Virus was isolated from all the reacting sheep and was detected sometimes as early as 1 day PI and as late as 30 days PI. A high titre of log10 4.0 to 7.0 per 1 ml of blood was recorded during several consecutive days before and after the onset of clinical signs. There seemed to be an inverse ratio between the amount of virus inoculated and the number of days the virus persisted in the bloodstream. The neutralisation index in day 22 serum samples was 3.5 to 4.5. Virus was isolated from some of the reacting sheep on the day that these antibody levels were recorded. Since the comparative simultaneous titrations of BT virus in sheep and in CE yielded similar results, the IV inoculation of CE is advocated as the routine method to be employed for laboratory diagnosis of this disease."} {"id": "PMID:169791", "title": "The epizootiology of bluetongue: the African situation.", "content": "Bluetongue virus is transmitted biologically by various species of Culicoides, notably C. pallidipennis and C. variipennis. Factors such as rainfall, temperature and relative altitude, which influence the breeding of the insect vectors also govern the incidence and distribution of the disease. The host range of bluetongue virus includes sheep, cattle, goats and various antelopes. Many other, as yet unidentified hosts could perhaps harbour the virus and influence the epizootiology of the disease. The close relationship between C. pallidipennis and cattle is indicated and the efficient mechanism for virus maintenance which this relationship constitutes is emphasised. It is further postulated that sheep are not essential for the continued survival of bluetongue virus, but merely function as accidental or indicator hosts.", "contents": "The epizootiology of bluetongue: the African situation. Bluetongue virus is transmitted biologically by various species of Culicoides, notably C. pallidipennis and C. variipennis. Factors such as rainfall, temperature and relative altitude, which influence the breeding of the insect vectors also govern the incidence and distribution of the disease. The host range of bluetongue virus includes sheep, cattle, goats and various antelopes. Many other, as yet unidentified hosts could perhaps harbour the virus and influence the epizootiology of the disease. The close relationship between C. pallidipennis and cattle is indicated and the efficient mechanism for virus maintenance which this relationship constitutes is emphasised. It is further postulated that sheep are not essential for the continued survival of bluetongue virus, but merely function as accidental or indicator hosts."} {"id": "PMID:169793", "title": "Epizootiology of bluetongue: the situation in the United States of America.", "content": "Bluetongue was first reported in the United States in 1948 in sheep in Texas. The virus has now been isolated from sheep in 19 States. When the disease first occurs in a flock, the morbidity may reach 50 to 75% and mortality 20 to 50%. In subsequent years, the morbidity may be only 1 to 2% with very few deaths. Difference in breed susceptibility has not been observed. Natural bluetongue infection has not been observed in Angora or dairy goats. Bluetongue virus was first isolated from cattle, in Oregon, in 1959. The virus has now been isolated from cattle in 13 States. In cattle, the disease is usually inapparent but can cause mild to severe clinical disease and neonatal losses. Natural clinical bluetongue has also been reported in bighorn sheep, exotic ruminants in a zoo, mule deer, and white-tailed deer. Serological evidence of exposure to the virus has also been found in other species of ruminants in the wild. Inoculation of virulent bluetongue virus, vaccine virus, or natural disease can cause congenital deformities and neonatal losses in calves, lambs, and white-tailed deer fawns. Culicoides is considered the important insect vector of bluetongue. The virus has also been isolated from sheep keds and cattle lice. U.S. field strains of the virus fit into four serologic groups. No cross reactions were found between bluetongue and epizootic haemorrhagic disease of deer viruses. Cattle are considered significant virus reservoirs. It is necessary to use washed erythrocytes, rather than whole blood, and to inoculate susceptible sheep, rather than embryonated chicken eggs, to detect longer-term viraemia in cattle.", "contents": "Epizootiology of bluetongue: the situation in the United States of America. Bluetongue was first reported in the United States in 1948 in sheep in Texas. The virus has now been isolated from sheep in 19 States. When the disease first occurs in a flock, the morbidity may reach 50 to 75% and mortality 20 to 50%. In subsequent years, the morbidity may be only 1 to 2% with very few deaths. Difference in breed susceptibility has not been observed. Natural bluetongue infection has not been observed in Angora or dairy goats. Bluetongue virus was first isolated from cattle, in Oregon, in 1959. The virus has now been isolated from cattle in 13 States. In cattle, the disease is usually inapparent but can cause mild to severe clinical disease and neonatal losses. Natural clinical bluetongue has also been reported in bighorn sheep, exotic ruminants in a zoo, mule deer, and white-tailed deer. Serological evidence of exposure to the virus has also been found in other species of ruminants in the wild. Inoculation of virulent bluetongue virus, vaccine virus, or natural disease can cause congenital deformities and neonatal losses in calves, lambs, and white-tailed deer fawns. Culicoides is considered the important insect vector of bluetongue. The virus has also been isolated from sheep keds and cattle lice. U.S. field strains of the virus fit into four serologic groups. No cross reactions were found between bluetongue and epizootic haemorrhagic disease of deer viruses. Cattle are considered significant virus reservoirs. It is necessary to use washed erythrocytes, rather than whole blood, and to inoculate susceptible sheep, rather than embryonated chicken eggs, to detect longer-term viraemia in cattle."} {"id": "PMID:169794", "title": "The control of bluetongue in an enzootic situation.", "content": "On account of the wide host range of bluetongue virus and its biological transmission by insects, control of the disease in an enzootic situation is based primarily on the active immunisation of susceptible animals as well as on the prevention of contact between the insect vectors and the susceptible hosts. In spite of their unquestionable value, the egg attenuated vaccines which are currently employed for prophylactic immunisation, have certain shortcomings. The existence of 16 known serotypes of bluetongue virus makes it difficult to achieve a very wide spectrum of immunity in sheep vaccinated once or twice only. The problems which are experienced with the immunisation of lambs born in spring are indicated. The present vaccine can also present problems when used in breeding animals. Furthermore, the costs involved in the annual vaccination of large numbers of animals are considerable. The need for a vaccine for cattle is indicated. Work is also being conducted at present on the development of an inactivated vaccine for use in sheep. The use of novel virological techniques may aid in the future development of absolutely safe and highly efficient vaccines against bluetongue.", "contents": "The control of bluetongue in an enzootic situation. On account of the wide host range of bluetongue virus and its biological transmission by insects, control of the disease in an enzootic situation is based primarily on the active immunisation of susceptible animals as well as on the prevention of contact between the insect vectors and the susceptible hosts. In spite of their unquestionable value, the egg attenuated vaccines which are currently employed for prophylactic immunisation, have certain shortcomings. The existence of 16 known serotypes of bluetongue virus makes it difficult to achieve a very wide spectrum of immunity in sheep vaccinated once or twice only. The problems which are experienced with the immunisation of lambs born in spring are indicated. The present vaccine can also present problems when used in breeding animals. Furthermore, the costs involved in the annual vaccination of large numbers of animals are considerable. The need for a vaccine for cattle is indicated. Work is also being conducted at present on the development of an inactivated vaccine for use in sheep. The use of novel virological techniques may aid in the future development of absolutely safe and highly efficient vaccines against bluetongue."} {"id": "PMID:169796", "title": "Bluetongue certification -- Australian policy.", "content": "Australian quarantine policies with respect to BT are based on regarding this disease as one of high risk and major potential economic importance to our ruminant population. There are deficiencies in our knowledge of world distribution, epidemiology and pathogenesis. There may be unknown vectors and unsuspected animal reservoir hosts. The international distribution of BT could be extending through the movements of insects or cattle. If introduced into Australia, the cattle and sheep populations would probably be at continuous risk as eradication would be difficult or impossible. Costs to the sheep industry at least could be high and productivity gravely affected. To reduce the probability of introduction, imports of ruminants and semen have, for the last 16 years, been restricted to a very small number of countries presumed free from BT. Future policies will almost certainly be based on these same considerations taking into account scientific advances in diagnosis and virus detection. The establishment of an off-shore high security quarantine station will facilitate imports of ruminants even from known BT-infected countries.", "contents": "Bluetongue certification -- Australian policy. Australian quarantine policies with respect to BT are based on regarding this disease as one of high risk and major potential economic importance to our ruminant population. There are deficiencies in our knowledge of world distribution, epidemiology and pathogenesis. There may be unknown vectors and unsuspected animal reservoir hosts. The international distribution of BT could be extending through the movements of insects or cattle. If introduced into Australia, the cattle and sheep populations would probably be at continuous risk as eradication would be difficult or impossible. Costs to the sheep industry at least could be high and productivity gravely affected. To reduce the probability of introduction, imports of ruminants and semen have, for the last 16 years, been restricted to a very small number of countries presumed free from BT. Future policies will almost certainly be based on these same considerations taking into account scientific advances in diagnosis and virus detection. The establishment of an off-shore high security quarantine station will facilitate imports of ruminants even from known BT-infected countries."} {"id": "PMID:169798", "title": "Control of bluetongue in an epizootic situation: Australian plans.", "content": "Epizootics of BT outside Africa have occurred in the Middle East, Indian subcontinent, Spain and Portugal, and the United States of America. The disease has only been eradicated from a major region once, this being Spain and Portugal in 1956-60 when it was achieved by quarantine, compulsory vaccination and slaughter of some infected animals. Because of the serious economic effect that BT would have on the Australian sheep industry the policy in this country is to attempt eradication, if at all feasible. The prospects of eradication will be greatly enhanced if the disease can be diagnosed quickly, when the outbreak is still localised. The laboratory diagnosis of BT involves inoculation of blood samples, collected from febrile animals on the suspect property, into groups of susceptible sheep in insect-proof quarters. The diagnosis would be confirmed at the reference laboratory in South Africa by serological and other identity tests. The diagnosis of an outbreak that originated in the northern cattle areas might be very difficult, because of the probable mild clinical nature of the disease in cattle. It is suggested that sentinel sheep flocks be maintained in these areas in strategic places near likely points of entry. Control measures, based on current knowledge of the epizootiology and pathogenesis of bluetongue; are discussed. The disease is transmitted by Culicoides that ingest infected blood from viraemic ruminants. Control is based on reducing the number of viraemic ruminants in the infected area, reducing the population density of Culicoides, and reducing the availability of susceptible ruminants. It is vital to prevent the movement of potentially infected ruminants to new localities. Contingent plans for the eradication of an epizootic of BT in Australia have been prepared. These call for the creation of two control zones. In the inner infected area, which extends for about five miles around known infected farms, there would be an intensive disinsection programme with aerial and ground spraying. Ruminants in the infected area would probably be slaughtered. The quarantine zone would extend for another 50 miles and in this area there would be prohibition of the movement of ruminants from farms. Regular clinical inspections and serological surveys would be carried out to detect secondary outbreaks. If control measures failed, it might be necessary to mount urgently a massive vaccination campaign to prevent disastrous losses to the Australian sheep industry. The difficulties in obtaining sufficient quantities of monovalent vaccine from overseas at short notice are discussed. Plans have been made to produce BT vaccine in Australia, in a specially designed high security laboratory, should the need arise.", "contents": "Control of bluetongue in an epizootic situation: Australian plans. Epizootics of BT outside Africa have occurred in the Middle East, Indian subcontinent, Spain and Portugal, and the United States of America. The disease has only been eradicated from a major region once, this being Spain and Portugal in 1956-60 when it was achieved by quarantine, compulsory vaccination and slaughter of some infected animals. Because of the serious economic effect that BT would have on the Australian sheep industry the policy in this country is to attempt eradication, if at all feasible. The prospects of eradication will be greatly enhanced if the disease can be diagnosed quickly, when the outbreak is still localised. The laboratory diagnosis of BT involves inoculation of blood samples, collected from febrile animals on the suspect property, into groups of susceptible sheep in insect-proof quarters. The diagnosis would be confirmed at the reference laboratory in South Africa by serological and other identity tests. The diagnosis of an outbreak that originated in the northern cattle areas might be very difficult, because of the probable mild clinical nature of the disease in cattle. It is suggested that sentinel sheep flocks be maintained in these areas in strategic places near likely points of entry. Control measures, based on current knowledge of the epizootiology and pathogenesis of bluetongue; are discussed. The disease is transmitted by Culicoides that ingest infected blood from viraemic ruminants. Control is based on reducing the number of viraemic ruminants in the infected area, reducing the population density of Culicoides, and reducing the availability of susceptible ruminants. It is vital to prevent the movement of potentially infected ruminants to new localities. Contingent plans for the eradication of an epizootic of BT in Australia have been prepared. These call for the creation of two control zones. In the inner infected area, which extends for about five miles around known infected farms, there would be an intensive disinsection programme with aerial and ground spraying. Ruminants in the infected area would probably be slaughtered. The quarantine zone would extend for another 50 miles and in this area there would be prohibition of the movement of ruminants from farms. Regular clinical inspections and serological surveys would be carried out to detect secondary outbreaks. If control measures failed, it might be necessary to mount urgently a massive vaccination campaign to prevent disastrous losses to the Australian sheep industry. The difficulties in obtaining sufficient quantities of monovalent vaccine from overseas at short notice are discussed. Plans have been made to produce BT vaccine in Australia, in a specially designed high security laboratory, should the need arise."} {"id": "PMID:169799", "title": "Eradication of subgroups A and B lymphoid leukosis virus from commercial poultry breeding flocks.", "content": "A specific-pathogen-free pedigreed breeding population of White Leghorns was determined to be free of lymphoid leukosis subgroups (LL-A and LL-B) on the basis of the standard resistance-inducing factor (RIF) test of sera of individual birds. The fourth pedigreed generation (G-4) was the first to test free of viruses of both sub-groups. In three subsequent pedigreed generations (G-5 through G-7) no viremic birds were found. The RIF test of sera was also used to detect carriers infected with LL-A and LL-B in sample populations of commercial broiler, brown-egg layer, and other White Leghorn breeding lines. When only known nonviremic dams were used for reproduction, in only one instance were viremic birds detected in samples of their progeny in succeeding generations. Some implications for a virus-free breeding program are discussed.", "contents": "Eradication of subgroups A and B lymphoid leukosis virus from commercial poultry breeding flocks. A specific-pathogen-free pedigreed breeding population of White Leghorns was determined to be free of lymphoid leukosis subgroups (LL-A and LL-B) on the basis of the standard resistance-inducing factor (RIF) test of sera of individual birds. The fourth pedigreed generation (G-4) was the first to test free of viruses of both sub-groups. In three subsequent pedigreed generations (G-5 through G-7) no viremic birds were found. The RIF test of sera was also used to detect carriers infected with LL-A and LL-B in sample populations of commercial broiler, brown-egg layer, and other White Leghorn breeding lines. When only known nonviremic dams were used for reproduction, in only one instance were viremic birds detected in samples of their progeny in succeeding generations. Some implications for a virus-free breeding program are discussed."} {"id": "PMID:169800", "title": "Morphological changes of chicken tracheas and tracheal organ cultures infected with avian infectious bronchitis virus studied in scanning electron microscope.", "content": "Chicken tracheas infected in vitro in organ culture and in vivo with avian infectious bronchitis virus (IBV) were studied by scanning electron microscopy. In in vitro infection in organ culture the columnar epithelial cells lining the tracheal ring lost their cilia and rounded up in 48 hr. There were numerous elevations and holes on the infected cell surface. Subsequently the cells sloughed off. In in vivo infection the tracheal epithelial cells lost their cilia in 4 days. These cells without cilia appeared bulging, and the surfaces were covered with microvillus-like structures. Subsequently a pseudomembrane was present in most areas. In 10 days postinfection the cilia started regenerating, and in 12 days postinfection there was complete regeneration of cells and cilia, giving a normal appearance to the trachea.", "contents": "Morphological changes of chicken tracheas and tracheal organ cultures infected with avian infectious bronchitis virus studied in scanning electron microscope. Chicken tracheas infected in vitro in organ culture and in vivo with avian infectious bronchitis virus (IBV) were studied by scanning electron microscopy. In in vitro infection in organ culture the columnar epithelial cells lining the tracheal ring lost their cilia and rounded up in 48 hr. There were numerous elevations and holes on the infected cell surface. Subsequently the cells sloughed off. In in vivo infection the tracheal epithelial cells lost their cilia in 4 days. These cells without cilia appeared bulging, and the surfaces were covered with microvillus-like structures. Subsequently a pseudomembrane was present in most areas. In 10 days postinfection the cilia started regenerating, and in 12 days postinfection there was complete regeneration of cells and cilia, giving a normal appearance to the trachea."} {"id": "PMID:169801", "title": "Rous sarcoma regression in chickens resistant or susceptible to Marek's disease.", "content": "In 4 experiments, strains of chickens relatively susceptible (S-strain, P-line) or resistant (N-line, PDRC) to Marek's disease (MD) were challenged with Rous sarcoma virus (RSV) at 6-8 weeks old. RSV tumors occurred in 94-100% of the birds in each strain, but the number with tumors that regressed during the 40-46-day experiment varied from 7% (S-strain) to 91% (PDRC). The N-line and P-line birds, derived from a random-bred flock with selection only for susceptibility or resistance to MD, regressed their tumors at about equal rates (respectively 59 and 65%). Thus, although the genetic strains differed in ability to regress RSV tumors, the difference was not necessarily related to genetic resistance or susceptibility to MD. Other birds in 2 of the experiments, infected 2-4 weeks earlier with JM or GA isolants of MD virus, had significantly (P less than 0.01) lower incidence of RSV tumor regression than did controls provided that they developed gross lesions of MD.", "contents": "Rous sarcoma regression in chickens resistant or susceptible to Marek's disease. In 4 experiments, strains of chickens relatively susceptible (S-strain, P-line) or resistant (N-line, PDRC) to Marek's disease (MD) were challenged with Rous sarcoma virus (RSV) at 6-8 weeks old. RSV tumors occurred in 94-100% of the birds in each strain, but the number with tumors that regressed during the 40-46-day experiment varied from 7% (S-strain) to 91% (PDRC). The N-line and P-line birds, derived from a random-bred flock with selection only for susceptibility or resistance to MD, regressed their tumors at about equal rates (respectively 59 and 65%). Thus, although the genetic strains differed in ability to regress RSV tumors, the difference was not necessarily related to genetic resistance or susceptibility to MD. Other birds in 2 of the experiments, infected 2-4 weeks earlier with JM or GA isolants of MD virus, had significantly (P less than 0.01) lower incidence of RSV tumor regression than did controls provided that they developed gross lesions of MD."} {"id": "PMID:169802", "title": "Growth of Mycoplasma synoviae in a medium supplemented with nicotinamide instead of B-nicotinamide adenine dinucleotide.", "content": "The cultivation of Mycoplasma synoviae (MS) on growth medium requires supplementation with B-nicotinamide adenine dinucleotide (NAD), an expensive and relatively unstable compound. Strains of MS were adapted (selected) to grow in a medium supplemented instead with nicotinamide, a stable and inexpensive substance that can be heat-sterilized in the medium without impairing its growth-promoting properties. MS plate agglutinating antigens grown in nicotinamide-enriched media were comparable in yield and serological reaction to antigens grown with NAD supplementation.", "contents": "Growth of Mycoplasma synoviae in a medium supplemented with nicotinamide instead of B-nicotinamide adenine dinucleotide. The cultivation of Mycoplasma synoviae (MS) on growth medium requires supplementation with B-nicotinamide adenine dinucleotide (NAD), an expensive and relatively unstable compound. Strains of MS were adapted (selected) to grow in a medium supplemented instead with nicotinamide, a stable and inexpensive substance that can be heat-sterilized in the medium without impairing its growth-promoting properties. MS plate agglutinating antigens grown in nicotinamide-enriched media were comparable in yield and serological reaction to antigens grown with NAD supplementation."} {"id": "PMID:169803", "title": "Avian encephalomyelitis virus in chicken pancreatic cell cultures.", "content": "Monolayer cell cultures consisting of epithelioid cells were made from pancreatic tissue of 10-to-13-day-old chicks. The maximum virus titer of the cell-culture fluid was obtained 8 days after inoculation with an embryo-adapted avian encephalomyelitis virus (AEV). Virus titers also increased in cell cultures inoculated with a chick-pancreas-passed AEV or a field isolant. Cell cultures inoculated with 3 strains of AEV maintained virus titers of 10(2.9)-10(3.7) 50% embryo-infective doses/ml for 15-20 days. In other cell cultures from pancreatic tissues of chicks preinfected orally with the chick-pancreas-passed AEV or the field isolant, the virus titers decreased for several days after cultivation and thereafter increased and persisted until at least the 25th or 30th day. Neither a cytopathic effect nor any inclusion body was observed in the cell cultures infected with AEV. No AEV-antigen-positive cell was detected by direct fluorescent-antibody technique.", "contents": "Avian encephalomyelitis virus in chicken pancreatic cell cultures. Monolayer cell cultures consisting of epithelioid cells were made from pancreatic tissue of 10-to-13-day-old chicks. The maximum virus titer of the cell-culture fluid was obtained 8 days after inoculation with an embryo-adapted avian encephalomyelitis virus (AEV). Virus titers also increased in cell cultures inoculated with a chick-pancreas-passed AEV or a field isolant. Cell cultures inoculated with 3 strains of AEV maintained virus titers of 10(2.9)-10(3.7) 50% embryo-infective doses/ml for 15-20 days. In other cell cultures from pancreatic tissues of chicks preinfected orally with the chick-pancreas-passed AEV or the field isolant, the virus titers decreased for several days after cultivation and thereafter increased and persisted until at least the 25th or 30th day. Neither a cytopathic effect nor any inclusion body was observed in the cell cultures infected with AEV. No AEV-antigen-positive cell was detected by direct fluorescent-antibody technique."} {"id": "PMID:169808", "title": "Transformation of cultured rat liver cells by murine sarcoma viruses.", "content": "Cultured liver cells (TRL-2 cells), originating from a BD-6 rat, an inbred black rat strain, and possessing several marker enzymes, and characteristic ultrastructures of hepatic cells, were infected with murine sarcoma viruses (MSV: Kirsten and Gazdar strains). On day 5-6 after virus inoculation, the monolayered epithelial cells focally began to pile up forming small polypoid projections, and on day 7 round-shaped cells were released from the polypoid foci. These cells first grew in a chain or as an islet of cells, but at confluent stage, they grew in suspension with some epithelioid cells attaching to the bottom of the flasks. Virus titer and focus count gave a one-hit dose response. However, 100 to 1,000 times higher titer of MSV was necessary to transform TRL-2 cells than to transform syngeneic fibroblasts, which suggested a higher repression of MSV in the epithelial cells. Those transformed TRL-2 cells showed only murine group-specific virual antigens. One of the minimal MSV-producing, MSV-transformed TRL-2 lines was subcutaneously transplanted into weanling BD-6 rats, producing progressively growing tumors with possible histology of hepatocellular carcinoma.", "contents": "Transformation of cultured rat liver cells by murine sarcoma viruses. Cultured liver cells (TRL-2 cells), originating from a BD-6 rat, an inbred black rat strain, and possessing several marker enzymes, and characteristic ultrastructures of hepatic cells, were infected with murine sarcoma viruses (MSV: Kirsten and Gazdar strains). On day 5-6 after virus inoculation, the monolayered epithelial cells focally began to pile up forming small polypoid projections, and on day 7 round-shaped cells were released from the polypoid foci. These cells first grew in a chain or as an islet of cells, but at confluent stage, they grew in suspension with some epithelioid cells attaching to the bottom of the flasks. Virus titer and focus count gave a one-hit dose response. However, 100 to 1,000 times higher titer of MSV was necessary to transform TRL-2 cells than to transform syngeneic fibroblasts, which suggested a higher repression of MSV in the epithelial cells. Those transformed TRL-2 cells showed only murine group-specific virual antigens. One of the minimal MSV-producing, MSV-transformed TRL-2 lines was subcutaneously transplanted into weanling BD-6 rats, producing progressively growing tumors with possible histology of hepatocellular carcinoma."} {"id": "PMID:169804", "title": "Serotyping of avian infectious bronchitis viruses by the virus-neutralization test.", "content": "The antigenic relationships of 12 strains of infectious bronchitis virus (IBV) were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. Such a procedure consists of reciprocal neutralization tests performed by reacting 32-320 EID50 or plaque-forming units of virus with 20 antibody units of antiserum. Eight serologic groups were identified by chicken embryo assay, and 4 by plaque-reduction (90%). In general, serologic groupings were not distinct but reflected numerous intergroup relationships. The contrasting results exhibited by indicator systems are viewed as differences in the accuracy of the methods employed. It is suggested that before an IBV classification scheme can be proposed, agreement must be reached on the most suitable indicator system, techniques must be standardized, and reference viruses and antisera distributed to several institutions for comparison testing. In addition, cross-protection studies are needed to determine the importance of IBV serotypes and/or variants on vaccine efficacy.", "contents": "Serotyping of avian infectious bronchitis viruses by the virus-neutralization test. The antigenic relationships of 12 strains of infectious bronchitis virus (IBV) were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. Such a procedure consists of reciprocal neutralization tests performed by reacting 32-320 EID50 or plaque-forming units of virus with 20 antibody units of antiserum. Eight serologic groups were identified by chicken embryo assay, and 4 by plaque-reduction (90%). In general, serologic groupings were not distinct but reflected numerous intergroup relationships. The contrasting results exhibited by indicator systems are viewed as differences in the accuracy of the methods employed. It is suggested that before an IBV classification scheme can be proposed, agreement must be reached on the most suitable indicator system, techniques must be standardized, and reference viruses and antisera distributed to several institutions for comparison testing. In addition, cross-protection studies are needed to determine the importance of IBV serotypes and/or variants on vaccine efficacy."} {"id": "PMID:169811", "title": "T-lymphocyte cell lines derived from patients with acute lymphoblastic leukemia.", "content": "Several lymphoid cell lines with thymus-dependent lymphocyte (T-cell) characteristics have been established from 2 patients with acute lymphoblastic leukemia (ALL). These cell lines are considered to be leukemic T-cells on the basis of their abnormal chromosome constitution, growth in heterologous animals, ability to form rosettes with sheep red blood cells and the absence of immunoglobulin production, and destruction by antithymus cell sera. Sera from patients with leukemia did not react with these cultured cells but there was a strong reaction with infectious mononucleosis sera despite the fact that the cultured leukemia T-cells had no detectable Epstein-Barr virus (EBV) nor its genome.", "contents": "T-lymphocyte cell lines derived from patients with acute lymphoblastic leukemia. Several lymphoid cell lines with thymus-dependent lymphocyte (T-cell) characteristics have been established from 2 patients with acute lymphoblastic leukemia (ALL). These cell lines are considered to be leukemic T-cells on the basis of their abnormal chromosome constitution, growth in heterologous animals, ability to form rosettes with sheep red blood cells and the absence of immunoglobulin production, and destruction by antithymus cell sera. Sera from patients with leukemia did not react with these cultured cells but there was a strong reaction with infectious mononucleosis sera despite the fact that the cultured leukemia T-cells had no detectable Epstein-Barr virus (EBV) nor its genome."} {"id": "PMID:169812", "title": "Biochemical and immunologic characterization of an oncornavirus glycoprotein.", "content": "Studies were carried out on an oncogenic C-type virus, Scripps leukemia virus (SLV), produced by a lymphoblastoid cell line (SCRF 60A) from a New Zealand Black (NZB) mouse. A 70,000 dalton glycoprotein on the virion surface constitutes about 10% of the virion amino acids and about 50% of the glucosamine. The protein can be isolated from surface iodinated SCRF 60A cells as well as from a line of nonproducer cells. This protein reacts with sera which neutralize Moloney, Kirsten, Rauscher, AKR, and, of course, Scripps viruses. These data suggest that this is the principal antigen detected by immunofluorescence on the surface of cells infected with murine leukemia virus (MuLV) and that this antigen may be involved in virus neutralization.", "contents": "Biochemical and immunologic characterization of an oncornavirus glycoprotein. Studies were carried out on an oncogenic C-type virus, Scripps leukemia virus (SLV), produced by a lymphoblastoid cell line (SCRF 60A) from a New Zealand Black (NZB) mouse. A 70,000 dalton glycoprotein on the virion surface constitutes about 10% of the virion amino acids and about 50% of the glucosamine. The protein can be isolated from surface iodinated SCRF 60A cells as well as from a line of nonproducer cells. This protein reacts with sera which neutralize Moloney, Kirsten, Rauscher, AKR, and, of course, Scripps viruses. These data suggest that this is the principal antigen detected by immunofluorescence on the surface of cells infected with murine leukemia virus (MuLV) and that this antigen may be involved in virus neutralization."} {"id": "PMID:169813", "title": "Spontaneous Herpesvirus saimiri lymphoma in owl monkeys.", "content": "Three examples of spontaneous malignant lymphoma were observed in owl monkeys 23, 81, and 183 days after arrival in our laboratories. The pathological features of the disease were analogous to experimentally induced Herpesvirus saimiri lymphoma. H. saimiri was recovered from 2 animals (it was not attempted from one case) and one isolate was shown to reproduce characteristic H. saimiri malignant lymphoma. Each monkey originated in Peru in contrast to our usual source of owl monkeys which originate in Barranquilla, Colombia. Samples collected from owl monkeys in Peru did not reveal antibodies to H. saimiri nor were virus isolated from cocultured leukocytes. Squirrel monkeys in the same geographical location all carried H. saimiri. The observations indicate that H. saimiri lymphoma can occur as a spontaneous disease and that the virus can cross the same taxonomic lines in nature as in the laboratory.", "contents": "Spontaneous Herpesvirus saimiri lymphoma in owl monkeys. Three examples of spontaneous malignant lymphoma were observed in owl monkeys 23, 81, and 183 days after arrival in our laboratories. The pathological features of the disease were analogous to experimentally induced Herpesvirus saimiri lymphoma. H. saimiri was recovered from 2 animals (it was not attempted from one case) and one isolate was shown to reproduce characteristic H. saimiri malignant lymphoma. Each monkey originated in Peru in contrast to our usual source of owl monkeys which originate in Barranquilla, Colombia. Samples collected from owl monkeys in Peru did not reveal antibodies to H. saimiri nor were virus isolated from cocultured leukocytes. Squirrel monkeys in the same geographical location all carried H. saimiri. The observations indicate that H. saimiri lymphoma can occur as a spontaneous disease and that the virus can cross the same taxonomic lines in nature as in the laboratory."} {"id": "PMID:169814", "title": "Experiments to vaccinate marmoset monkeys against malignant lymphoma.", "content": "Humoral antibodies can be induced in cotton topped (CT) marmosets with killed Herpesvirus saimiri (HVS) vaccines. The serum antibodies delayed, but did not prevent, malignant lymphoma in actively and passively immunized monkeys after inoculation with 10(3.8)TCID50 of cell-free HVS. Experiments are in progress to determine whether the vaccines are able to protect against smaller challenge dosages of HVS. The immunized monkeys were not resistant against transplantation of tumor cells. Infection with Epstein-Barr virus (EBV) and Marek's disease virus (MDV) did not protect against the tumors caused by superinfection with HVS. Attenuation of HVS was not achieved by passaging the HVS genome through different monkey species.", "contents": "Experiments to vaccinate marmoset monkeys against malignant lymphoma. Humoral antibodies can be induced in cotton topped (CT) marmosets with killed Herpesvirus saimiri (HVS) vaccines. The serum antibodies delayed, but did not prevent, malignant lymphoma in actively and passively immunized monkeys after inoculation with 10(3.8)TCID50 of cell-free HVS. Experiments are in progress to determine whether the vaccines are able to protect against smaller challenge dosages of HVS. The immunized monkeys were not resistant against transplantation of tumor cells. Infection with Epstein-Barr virus (EBV) and Marek's disease virus (MDV) did not protect against the tumors caused by superinfection with HVS. Attenuation of HVS was not achieved by passaging the HVS genome through different monkey species."} {"id": "PMID:169815", "title": "Comparisons of surface markers on Herpesvirus-associated lymphoid cells of nonhuman primates and established human lymphoid cell lines.", "content": "Herpesvirus saimiri (HVS)-owl monkey lymphoid cells were found to have high levels of surface receptor for sheep erythrocytes and erythrocytes of 3 other species. These HVS-lymphoid cells lacked a receptor for modified complement. Lymphoid cells of one HVS-owl monkey line showed evidence for the presence of surface immunofluorescent staining with anti-kappa chain serum. Cells of an established HVS-marmoset lymphoid line had similar surface markers. Of 4 established human lymphoid cell lines, all lacked a receptor for sheep erythrocytes, 3 showed evidence for the presence of receptor for modified complement, and 3 showed immunofluorescent evidence for the presence on the surface of both heavy and light chain immunoglobulin. Preliminary data on an established Epstein-Barr virus (EBV)-owl monkey lymphoid cell line indicated a lack of receptor for sheep erythrocytes, presence of receptor for modified complement, and surface immunofluorescent staining with both anti-heavy and anti-light chain sera.", "contents": "Comparisons of surface markers on Herpesvirus-associated lymphoid cells of nonhuman primates and established human lymphoid cell lines. Herpesvirus saimiri (HVS)-owl monkey lymphoid cells were found to have high levels of surface receptor for sheep erythrocytes and erythrocytes of 3 other species. These HVS-lymphoid cells lacked a receptor for modified complement. Lymphoid cells of one HVS-owl monkey line showed evidence for the presence of surface immunofluorescent staining with anti-kappa chain serum. Cells of an established HVS-marmoset lymphoid line had similar surface markers. Of 4 established human lymphoid cell lines, all lacked a receptor for sheep erythrocytes, 3 showed evidence for the presence of receptor for modified complement, and 3 showed immunofluorescent evidence for the presence on the surface of both heavy and light chain immunoglobulin. Preliminary data on an established Epstein-Barr virus (EBV)-owl monkey lymphoid cell line indicated a lack of receptor for sheep erythrocytes, presence of receptor for modified complement, and surface immunofluorescent staining with both anti-heavy and anti-light chain sera."} {"id": "PMID:169816", "title": "EB virus: malignant lymphoma in cottontop marmosets following inoculation and recovery of the virus from cells of an experimental tumor maintained in organ culture.", "content": "The oncogenic potential of Epstein-Barr virus (EBV) was investigated in cottontop marmosets. Neoplasia resembling human malignant lymphomas, reticulum cell sarcoma type, occurred following inoculation of materials containing EBV. One of 4 monkeys that received autologous cells transformed in vitro by EBV developed lymphoma in mesenteric lymph nodes seven and one-half months after inoculation. Three of 4 marmosets inoculated with cell-free EBV developed lymphoma. The latent period for given with EBV accelerated the course of disease. Nevertheless malignant lymphoma occurred in an animal given only cell-free virus. Six of 8 marmosets inoculated with EBV demonstrated antibodies to the virus. Four marmosets not exposed to the virus, of which 2 received immunosuppressive drugs, have not developed tumors, nor EBV antibodies. EBV antigen detectable by immunofluorescences has been found in 2% of cells shed from one tumor maintained in organ culture. These results imply that EBV is capable of inducing malignant lymphoma in at least one primate species. Additional experimental evidence is required, however, before its oncogenic capacity in this host can be accepted without reservation.", "contents": "EB virus: malignant lymphoma in cottontop marmosets following inoculation and recovery of the virus from cells of an experimental tumor maintained in organ culture. The oncogenic potential of Epstein-Barr virus (EBV) was investigated in cottontop marmosets. Neoplasia resembling human malignant lymphomas, reticulum cell sarcoma type, occurred following inoculation of materials containing EBV. One of 4 monkeys that received autologous cells transformed in vitro by EBV developed lymphoma in mesenteric lymph nodes seven and one-half months after inoculation. Three of 4 marmosets inoculated with cell-free EBV developed lymphoma. The latent period for given with EBV accelerated the course of disease. Nevertheless malignant lymphoma occurred in an animal given only cell-free virus. Six of 8 marmosets inoculated with EBV demonstrated antibodies to the virus. Four marmosets not exposed to the virus, of which 2 received immunosuppressive drugs, have not developed tumors, nor EBV antibodies. EBV antigen detectable by immunofluorescences has been found in 2% of cells shed from one tumor maintained in organ culture. These results imply that EBV is capable of inducing malignant lymphoma in at least one primate species. Additional experimental evidence is required, however, before its oncogenic capacity in this host can be accepted without reservation."} {"id": "PMID:169817", "title": "A comparative study on the presence of C-type viral particles in placentas from primates and other animals.", "content": "C-type particles are found in human, baboon, marmoset, rhesus, patas, and cynomolgus monkeys. A cebus monkey and two chimpanzee placentas have failed thus far to show the presence of these particles. Of the nonprimate tissues examined one mouse and one guinea pig placenta were positive whereas a rabbit placenta was negative. Variations in number of particles present in tissues as well as number of animals of a given species containing particles are noted. The isolation of foamyviruses from placenta cultures makes critical evaluation and interpretation of findings imperative. Several considerations suggest that the presence of foamyviruses is coincidental.", "contents": "A comparative study on the presence of C-type viral particles in placentas from primates and other animals. C-type particles are found in human, baboon, marmoset, rhesus, patas, and cynomolgus monkeys. A cebus monkey and two chimpanzee placentas have failed thus far to show the presence of these particles. Of the nonprimate tissues examined one mouse and one guinea pig placenta were positive whereas a rabbit placenta was negative. Variations in number of particles present in tissues as well as number of animals of a given species containing particles are noted. The isolation of foamyviruses from placenta cultures makes critical evaluation and interpretation of findings imperative. Several considerations suggest that the presence of foamyviruses is coincidental."} {"id": "PMID:169818", "title": "Human amnion and lung tissue culture systems for possible detection and study of human RNA tumor viruses.", "content": "A human lung and an amnion cell line were identified as highly susceptible to transformation by the rhabdomyosarcoma-114 (RD-114) virus pseudotype of murine sarcoma virus (MSV). MSV transformation on these two cell lines demonstrated a) \"one-hit\" kinetics with an MSV stock which contained a 100-fold excess of MSV over its detectable associate RD-114 helper virus and b) only a slight increase (2X) in focus-forming titers by the addition of optimal concentrations of RD-114 helper virus. These findings indicated that the primary MSV interaction with those amnion and lung cells was that of non-productive transformation; and this was confirmed by the isolation of sarcoma-positive leukemia (helper) virus-negative (S+Lminus) cells from cloned terminal foci of MSV transformed human amnion and lung cells. These MSV-susceptible human cell lines are the first human cells identified as capable of demonstrating the defective nature of MSV. Human candidate oncornaviruses have not, however, been detected to date with the use of normal lung and amnion cells and their S+Lminus derivatives as indicator systems. These cell lines were useful for the isolation and identification of a new RD-114-like virus from a cat cell line.", "contents": "Human amnion and lung tissue culture systems for possible detection and study of human RNA tumor viruses. A human lung and an amnion cell line were identified as highly susceptible to transformation by the rhabdomyosarcoma-114 (RD-114) virus pseudotype of murine sarcoma virus (MSV). MSV transformation on these two cell lines demonstrated a) \"one-hit\" kinetics with an MSV stock which contained a 100-fold excess of MSV over its detectable associate RD-114 helper virus and b) only a slight increase (2X) in focus-forming titers by the addition of optimal concentrations of RD-114 helper virus. These findings indicated that the primary MSV interaction with those amnion and lung cells was that of non-productive transformation; and this was confirmed by the isolation of sarcoma-positive leukemia (helper) virus-negative (S+Lminus) cells from cloned terminal foci of MSV transformed human amnion and lung cells. These MSV-susceptible human cell lines are the first human cells identified as capable of demonstrating the defective nature of MSV. Human candidate oncornaviruses have not, however, been detected to date with the use of normal lung and amnion cells and their S+Lminus derivatives as indicator systems. These cell lines were useful for the isolation and identification of a new RD-114-like virus from a cat cell line."} {"id": "PMID:169819", "title": "Complement-fixation-inhibition as a test for antibodies in cats and humans to C-type RNA tumor virus antigen.", "content": "The complement-fixation-inhibition (CFI) test was evaluated as a means of detecting humoral antibodies in cat sera and in human sera to mammalian C-type RNA virus interspecies antigen(s). CFI antibody titers of greater than or equal 1:2 were detected in sera from all tumor bearing (23) and normal cats (23), however, sera from most germ free cats were negative. When the same cat sera were tested for blocking antibody by the paired radioiodine labeled antibody technique the correlation between the radioimmune assay and CFI tests was 85%. Sera from 378 cancer patients and 193 normal people were tested for antibodies to the mammalian oncornavirus interspecies-specific antigen in the CFI test. This test used a rabbit antiserum prepared toward a purified feline leukemia virus (FeLV) interspecies antigen. Disrupted Rauscher murine leukemia virus (RLV) was used as source of interspecies antigen in the CFI test. A significantly (P=0.01) higher number of reactions occurred with sera from patients with lymphosarcoma (70.4%), osteosarcoma (41.0%), reticulum cell sarcoma (56.7%), and rhabdomyosarcoma (31.8%) as opposed to sera from normal individuals (6.2%). Of 51 sera from patients with acute lymphocytic leukemia 23.5% (P=0.05) were reactive. Of the sera from 88 breast cancer patients 22.7% reacted, as opposed to 7.8% of 116 normal females and 13.9% of 43 patients with benign breast disease. CFI antibody titers were shown to be dependent on RLV antigen concentration. Absorption with human A and B red blood cell (RBC) and Forssman antigen did not reduce the CFI titers in human sera whereas absorption with RLV reduced them significantly. By indirect radioimmunoelectrophoresis the antibody in selected human sera was shown to be an IgG.", "contents": "Complement-fixation-inhibition as a test for antibodies in cats and humans to C-type RNA tumor virus antigen. The complement-fixation-inhibition (CFI) test was evaluated as a means of detecting humoral antibodies in cat sera and in human sera to mammalian C-type RNA virus interspecies antigen(s). CFI antibody titers of greater than or equal 1:2 were detected in sera from all tumor bearing (23) and normal cats (23), however, sera from most germ free cats were negative. When the same cat sera were tested for blocking antibody by the paired radioiodine labeled antibody technique the correlation between the radioimmune assay and CFI tests was 85%. Sera from 378 cancer patients and 193 normal people were tested for antibodies to the mammalian oncornavirus interspecies-specific antigen in the CFI test. This test used a rabbit antiserum prepared toward a purified feline leukemia virus (FeLV) interspecies antigen. Disrupted Rauscher murine leukemia virus (RLV) was used as source of interspecies antigen in the CFI test. A significantly (P=0.01) higher number of reactions occurred with sera from patients with lymphosarcoma (70.4%), osteosarcoma (41.0%), reticulum cell sarcoma (56.7%), and rhabdomyosarcoma (31.8%) as opposed to sera from normal individuals (6.2%). Of 51 sera from patients with acute lymphocytic leukemia 23.5% (P=0.05) were reactive. Of the sera from 88 breast cancer patients 22.7% reacted, as opposed to 7.8% of 116 normal females and 13.9% of 43 patients with benign breast disease. CFI antibody titers were shown to be dependent on RLV antigen concentration. Absorption with human A and B red blood cell (RBC) and Forssman antigen did not reduce the CFI titers in human sera whereas absorption with RLV reduced them significantly. By indirect radioimmunoelectrophoresis the antibody in selected human sera was shown to be an IgG."} {"id": "PMID:169820", "title": "Immune response of healthy and leukemic cats to the feline oncornavirus-associated cell membrane antigen.", "content": "Feline leukemia is an infectious disease caused by a horizontally transmitted virus. Infection of animals or cultured cells with feline oncornaviruses results in the expression of a specific cell membrane antigen, feline oncornavirus-associated cell membrane antigen (FOCMA). The humoral antibody response to FOCMA is directly correlated with tumor progression. The measurement of this antibody is a useful tool for determining virus exposure. Using this procedure it was determined that cats living in leukemia \"cluster\" households as well as cats used as contact controls in virus injection experiments have a risk of infection of 90% or higher.", "contents": "Immune response of healthy and leukemic cats to the feline oncornavirus-associated cell membrane antigen. Feline leukemia is an infectious disease caused by a horizontally transmitted virus. Infection of animals or cultured cells with feline oncornaviruses results in the expression of a specific cell membrane antigen, feline oncornavirus-associated cell membrane antigen (FOCMA). The humoral antibody response to FOCMA is directly correlated with tumor progression. The measurement of this antibody is a useful tool for determining virus exposure. Using this procedure it was determined that cats living in leukemia \"cluster\" households as well as cats used as contact controls in virus injection experiments have a risk of infection of 90% or higher."} {"id": "PMID:169823", "title": "Quantitative and qualitative differences in DNA complementary to avian myeloblastosis virus between normal and leukemic chicken cells.", "content": "Hybridization of avian myeloblastosis virus (AMV) RNA with DNA immobilized on filters or in liquid with a vast DNA excess was used to measure the viral specific DNA sequences in chicken cells. Newly synthesized viral DNA (v-DNA) appears within an hour after infection of chicken embryo fibroblasts (CEF) with avian oncornaviruses. A fraction of newly synthesized v-DNA becomes integrated into the cellular genome and the remainder gradually disappears. A covalent linkage between v-DNA and cellular DNA was demonstrated to exist in CEF and in leukemic myeloblasts by alkaline sucrose velocity sedimentation. Hybridization of AMV RNA in DNA excess has revealed that there are 2 clases of viral specific sequences within normal as well as in leukemic cells. The 2 types of sequences differ in their rate of hybridization. The amount of both types of DNA sequences is about 2 times higher in leukemic cells than in normal cells. Both the fast- and slowly reacting sequences in leukemic cells exhibit a higher Tm (2 degrees C) than the respective DNA sequences in normal cells. Furthermore, when nucleotide sequences in AMV RNA complementary to normal DNA are removed first by exhaustive hybridization with normal DNA, the residual RNA only hybridizes with leukemic DNA but not with normal DNA. These results suggest that leukemic cells contain viral specific DNA sequences which are absent in normal cells. Endogenous v-DNA has been shown to be integrated in cellular DNA region(s) with a reiteration frequency of approximately 1,200 copies per cell and each integration unit appears to have a size approximately equivalent to the 35S RNA subunit of the viral genome. Viral sequences acquired after infection appear to be integrated in the unique region of cell DNA, or in tandem with the endogenous viral sequences.", "contents": "Quantitative and qualitative differences in DNA complementary to avian myeloblastosis virus between normal and leukemic chicken cells. Hybridization of avian myeloblastosis virus (AMV) RNA with DNA immobilized on filters or in liquid with a vast DNA excess was used to measure the viral specific DNA sequences in chicken cells. Newly synthesized viral DNA (v-DNA) appears within an hour after infection of chicken embryo fibroblasts (CEF) with avian oncornaviruses. A fraction of newly synthesized v-DNA becomes integrated into the cellular genome and the remainder gradually disappears. A covalent linkage between v-DNA and cellular DNA was demonstrated to exist in CEF and in leukemic myeloblasts by alkaline sucrose velocity sedimentation. Hybridization of AMV RNA in DNA excess has revealed that there are 2 clases of viral specific sequences within normal as well as in leukemic cells. The 2 types of sequences differ in their rate of hybridization. The amount of both types of DNA sequences is about 2 times higher in leukemic cells than in normal cells. Both the fast- and slowly reacting sequences in leukemic cells exhibit a higher Tm (2 degrees C) than the respective DNA sequences in normal cells. Furthermore, when nucleotide sequences in AMV RNA complementary to normal DNA are removed first by exhaustive hybridization with normal DNA, the residual RNA only hybridizes with leukemic DNA but not with normal DNA. These results suggest that leukemic cells contain viral specific DNA sequences which are absent in normal cells. Endogenous v-DNA has been shown to be integrated in cellular DNA region(s) with a reiteration frequency of approximately 1,200 copies per cell and each integration unit appears to have a size approximately equivalent to the 35S RNA subunit of the viral genome. Viral sequences acquired after infection appear to be integrated in the unique region of cell DNA, or in tandem with the endogenous viral sequences."} {"id": "PMID:169824", "title": "Control of reversion of Moloney virus sarcoma virus transformed cells.", "content": "Mouse cells transformed by the Moloney murine sarcoma virus (MSV) native to the species can give rise to revertants which are supersusceptible to a second cycle of transformation. The MSV retransformed cells can give rise to several complex functional states even after several cycles of cloning: a) Formation of sarcoma positive, leukemia negative (S+Lminus) type cells of which some sublines may be inducible for MSV by halogenated pyrimidines; b) detection of initially SminusLminus cells which spontaneously become transformed and S+Lminus; c) the derivation of flat murine leukemia virus positive (MuLV+) cells which have an atypical MuLV and may become MSV+ as well as MuLV+; d) the release of free MSV from some cell clones with an apparent absence of MuLV. A general feature of all the above variants is a failure of detection of spontaneous reversion occurring after the second cycle of transformation. The nature of MuLV spontaneously released is that of a poorly replicating MuLV which exhibits cross-interference with other MuLV pseudotypes of MSV and the envelope which is most similar to that of Moloney leukemia virus (MLV). The examination for spontaneous reversion in human S+Lminus cells transformed by the same type of genome capable of good frequency of reversion in mouse cells, did not yield human revertant cells.", "contents": "Control of reversion of Moloney virus sarcoma virus transformed cells. Mouse cells transformed by the Moloney murine sarcoma virus (MSV) native to the species can give rise to revertants which are supersusceptible to a second cycle of transformation. The MSV retransformed cells can give rise to several complex functional states even after several cycles of cloning: a) Formation of sarcoma positive, leukemia negative (S+Lminus) type cells of which some sublines may be inducible for MSV by halogenated pyrimidines; b) detection of initially SminusLminus cells which spontaneously become transformed and S+Lminus; c) the derivation of flat murine leukemia virus positive (MuLV+) cells which have an atypical MuLV and may become MSV+ as well as MuLV+; d) the release of free MSV from some cell clones with an apparent absence of MuLV. A general feature of all the above variants is a failure of detection of spontaneous reversion occurring after the second cycle of transformation. The nature of MuLV spontaneously released is that of a poorly replicating MuLV which exhibits cross-interference with other MuLV pseudotypes of MSV and the envelope which is most similar to that of Moloney leukemia virus (MLV). The examination for spontaneous reversion in human S+Lminus cells transformed by the same type of genome capable of good frequency of reversion in mouse cells, did not yield human revertant cells."} {"id": "PMID:169825", "title": "Detection of Epstein-Barr virus DNA in human tumors.", "content": "The presence of Epstein-Barr virus (EBV) DNA in biopsies of human tumors was tested by complementary RNA (cRNA) hybridization on membranes and DNA-DNA reassociation kinetics. DNA-DNA reassociation kinetics can detect as few as 1 EBV genome in every 50 cells, and the cRNA method can detect EBV genomes if 2 or more are present in a cell. Twenty-three out of 24 African Burkitt's lymphoma biopsies, 18 out of 23 African nasopharyngeal carcinomas (NPC), and 8 out of 24 other African tumors were positive for EBV DNA. Three cases of American Burkitt's lymphoma were tested by the cRNA method, and EBV DNA was not detected. Three out of 25 American tumors other than American Burkitt's lymphoma contained 0.1 to 0.3 genomes per cell of EBV DNA.", "contents": "Detection of Epstein-Barr virus DNA in human tumors. The presence of Epstein-Barr virus (EBV) DNA in biopsies of human tumors was tested by complementary RNA (cRNA) hybridization on membranes and DNA-DNA reassociation kinetics. DNA-DNA reassociation kinetics can detect as few as 1 EBV genome in every 50 cells, and the cRNA method can detect EBV genomes if 2 or more are present in a cell. Twenty-three out of 24 African Burkitt's lymphoma biopsies, 18 out of 23 African nasopharyngeal carcinomas (NPC), and 8 out of 24 other African tumors were positive for EBV DNA. Three cases of American Burkitt's lymphoma were tested by the cRNA method, and EBV DNA was not detected. Three out of 25 American tumors other than American Burkitt's lymphoma contained 0.1 to 0.3 genomes per cell of EBV DNA."} {"id": "PMID:169829", "title": "In vivo interactions between murine leukemia and sarcoma viruses.", "content": "Experiments have been performed with the aim of elucidating the nature and the extent of the in vivo interactions between murine leukemia viruses (MuLVs) and murine sarcoma virus (MSV). BALB/c and CBA mice, injected neonatally with Graffi or passage A Gross viruses (MuLV-Gi, MuLV-G), have been inoculated as young adults with murine sarcoma virus, Moloney strain (MSV-M). A higher percentage of nonregressing sarcomas appeared in these animals, sometimes accompanied simultaneously by leukemia. The immune reactivity of mice receiving MuLV-Gi at birth was found to be significantly depressed when evaluated by the hemolytic palque-forming cell (PFC) technique. However, in mice infected with MuLV-Gi and MSV-M the number of PFC ranged within the control values or slightly increased. The potentiation of MSV-M oncogenicity following infection with MuLV was studied in a more natural situation. Adult AKR mice, known to release endogenous MuLV continuously, were injected with MSV-M. The incidence of induced sarcomas was similar to that observed in control BALB/c mice inoculated with MSV-M. Moreover, tumors developed with a very long latent period. On the other hand, the great majority of tumors showed no regression and ultimately killed the host. Additional experiments, making use of immunologic manipulation of the host and Fl hybrids, suggest that the relative resistance to MSV-M oncogenesis in AKR mice is influenced by genetic and immunologic factors. MSV recovered from MSV-M-induced tumors in AKR and C58 mice was typed by highly specific mouse antisera. The results clearly showed that formation of a new MSV pseudotype occurred in vivo, the endogenous Gross virus acting as helper.", "contents": "In vivo interactions between murine leukemia and sarcoma viruses. Experiments have been performed with the aim of elucidating the nature and the extent of the in vivo interactions between murine leukemia viruses (MuLVs) and murine sarcoma virus (MSV). BALB/c and CBA mice, injected neonatally with Graffi or passage A Gross viruses (MuLV-Gi, MuLV-G), have been inoculated as young adults with murine sarcoma virus, Moloney strain (MSV-M). A higher percentage of nonregressing sarcomas appeared in these animals, sometimes accompanied simultaneously by leukemia. The immune reactivity of mice receiving MuLV-Gi at birth was found to be significantly depressed when evaluated by the hemolytic palque-forming cell (PFC) technique. However, in mice infected with MuLV-Gi and MSV-M the number of PFC ranged within the control values or slightly increased. The potentiation of MSV-M oncogenicity following infection with MuLV was studied in a more natural situation. Adult AKR mice, known to release endogenous MuLV continuously, were injected with MSV-M. The incidence of induced sarcomas was similar to that observed in control BALB/c mice inoculated with MSV-M. Moreover, tumors developed with a very long latent period. On the other hand, the great majority of tumors showed no regression and ultimately killed the host. Additional experiments, making use of immunologic manipulation of the host and Fl hybrids, suggest that the relative resistance to MSV-M oncogenesis in AKR mice is influenced by genetic and immunologic factors. MSV recovered from MSV-M-induced tumors in AKR and C58 mice was typed by highly specific mouse antisera. The results clearly showed that formation of a new MSV pseudotype occurred in vivo, the endogenous Gross virus acting as helper."} {"id": "PMID:169830", "title": "Hexose transport in sarcoma virus transformed cells.", "content": "Avian and mammalian fibroblast cultures transformed by type C sarcoma viruses show a dramatic enhancement of the rate of hexose transport at the beginning of transformation which is quantitatively and qualitatively different from that seen by variation in culture conditions of nontransformed control cells. The identification of this change as being a transport alteration independent of total glucose metabolism has been shown by use of nonmetabolizable analogues, 2-deoxyglucose, 3-O-methylglucose, and L-glucose. Increased transport rates were not dependent on levels of hexokinase activity. Transport studies of 3-O-methylglucose confirmed these conclusions and further revealed an additional altered nature of hexose transport after transformation by sarcoma virus. 3-O-methylglucose was not only transported more rapidly in the transformed cells than in the parental nontransformed cells, but the sugar \"infiltrated\" into the transformed cells despite the inhibitory effect of cytochalasin B. This was not seen with control cells. The sarcoma cells were also able to transport L-glucose in contrast to lack of uptake by nontransformed cells. Under conditions in which cell toxicity was not a factor, 2-deoxyglucose and several other sugars present in culture media inhibited transformation by sarcoma viruses. These same sugars reduced the incidence of sarcomas produced by virus in vivo when administered daily to test animals. The transport changes also correlate well with the transformed state as found by other laboratories using temperature-sensitive mutants and revertant cell lines. Collectively these data suggest that manipulation of transport systems may prove useful for control of certain malignancies.", "contents": "Hexose transport in sarcoma virus transformed cells. Avian and mammalian fibroblast cultures transformed by type C sarcoma viruses show a dramatic enhancement of the rate of hexose transport at the beginning of transformation which is quantitatively and qualitatively different from that seen by variation in culture conditions of nontransformed control cells. The identification of this change as being a transport alteration independent of total glucose metabolism has been shown by use of nonmetabolizable analogues, 2-deoxyglucose, 3-O-methylglucose, and L-glucose. Increased transport rates were not dependent on levels of hexokinase activity. Transport studies of 3-O-methylglucose confirmed these conclusions and further revealed an additional altered nature of hexose transport after transformation by sarcoma virus. 3-O-methylglucose was not only transported more rapidly in the transformed cells than in the parental nontransformed cells, but the sugar \"infiltrated\" into the transformed cells despite the inhibitory effect of cytochalasin B. This was not seen with control cells. The sarcoma cells were also able to transport L-glucose in contrast to lack of uptake by nontransformed cells. Under conditions in which cell toxicity was not a factor, 2-deoxyglucose and several other sugars present in culture media inhibited transformation by sarcoma viruses. These same sugars reduced the incidence of sarcomas produced by virus in vivo when administered daily to test animals. The transport changes also correlate well with the transformed state as found by other laboratories using temperature-sensitive mutants and revertant cell lines. Collectively these data suggest that manipulation of transport systems may prove useful for control of certain malignancies."} {"id": "PMID:169831", "title": "Biochemical properties of wild mouse oncornaviruses with lymphomagenic and neurotropic activities.", "content": "The close immunologic relation between the group-specific and polymerase proteins of the wild mouse derived and the established strains of mouse type C oncornaviruses, and the lack of any unusual structural polypeptide or RNA components in the wild mouse virions, eliminate the possibility of detectable contamination by a class of virus different from the mouse oncornavirus class in the wild mouse virus preparations. Liquid hybridization studies with a wild mouse viral 70S 3H-RNA and cellular DNA under conditions of DNA excess, suggest that a significant fraction but not all of the virus-specific nucleotide sequences is present in all normal and tumored wild mouse tissues tested. These virus related sequences may possibly be attributed to a hypothetical endogenous inherited type C virus genome(s) carried by all wild mice or to an infection by one or more but not all of the different exogenous strains of wild mouse type C viruses which could possibly be present in the virus preparation used. The findings are consistent with wild mouse derived type C viruses being either entirely exogenous or a mixture of endogenous and exogenous viruses. This interpretation is also consistent with the earlier observation that certain wild mouse type C viruses are exogenously transmitted, transplacentally, and via milk. The possible relation of the virus heterogeneity or the distinct characteristics of the virus surface molecules to the diverse pathogenicity of the wild mouse oncornaviruses is discussed.", "contents": "Biochemical properties of wild mouse oncornaviruses with lymphomagenic and neurotropic activities. The close immunologic relation between the group-specific and polymerase proteins of the wild mouse derived and the established strains of mouse type C oncornaviruses, and the lack of any unusual structural polypeptide or RNA components in the wild mouse virions, eliminate the possibility of detectable contamination by a class of virus different from the mouse oncornavirus class in the wild mouse virus preparations. Liquid hybridization studies with a wild mouse viral 70S 3H-RNA and cellular DNA under conditions of DNA excess, suggest that a significant fraction but not all of the virus-specific nucleotide sequences is present in all normal and tumored wild mouse tissues tested. These virus related sequences may possibly be attributed to a hypothetical endogenous inherited type C virus genome(s) carried by all wild mice or to an infection by one or more but not all of the different exogenous strains of wild mouse type C viruses which could possibly be present in the virus preparation used. The findings are consistent with wild mouse derived type C viruses being either entirely exogenous or a mixture of endogenous and exogenous viruses. This interpretation is also consistent with the earlier observation that certain wild mouse type C viruses are exogenously transmitted, transplacentally, and via milk. The possible relation of the virus heterogeneity or the distinct characteristics of the virus surface molecules to the diverse pathogenicity of the wild mouse oncornaviruses is discussed."} {"id": "PMID:169832", "title": "Immunological control of virus-induced tumors in primates.", "content": "Cells infected by oncogenic viruses may transform, may develop a latent carrier state, or may be destroyed but understanding of the control of the results of infection is incomplete. Even if cells transform, ultimate development of a tumor may be immunologically controlled. For example, cells of some marmoset species transform after infection with RNA tumor viruses, and animals react to the transformed cells with cell-mediated and humoral immune responses. Both virus specific and cross-reacting cell membrane antigens have been demonstrated. Immune deficiency accelerates tumor growth or causes recurrence of a regressing tumor. In contrast certain simian herpesvirus (Herpesvirus saimiri, HVS and Herpesvirus ateles, HVA), which cause no or minor disease in their natural hosts, induce lymphomas or lymphoblastic leukemias in other primate species. The immune response of the natural host species to HVS is greater than that of animals developing malignancies after experimental infection. HVS and HVA share many properties with Epstein-Barr virus (EBV) of man, including antigens appearing early and late during infection and their related antibody responses but no evidence exists that they induce malignancies in their natural hosts. However, if induction is as infrequent as that with EBV and Burkitt's lymphoma (BL), we have not observed sufficient numbers of squirrel or spider monkeys to have seen a BL-like tumor. Interference with the immune systems of animals carrying HVS or HVA may induce tumor development, and clarify our understanding of the relationships between EBV and BL.", "contents": "Immunological control of virus-induced tumors in primates. Cells infected by oncogenic viruses may transform, may develop a latent carrier state, or may be destroyed but understanding of the control of the results of infection is incomplete. Even if cells transform, ultimate development of a tumor may be immunologically controlled. For example, cells of some marmoset species transform after infection with RNA tumor viruses, and animals react to the transformed cells with cell-mediated and humoral immune responses. Both virus specific and cross-reacting cell membrane antigens have been demonstrated. Immune deficiency accelerates tumor growth or causes recurrence of a regressing tumor. In contrast certain simian herpesvirus (Herpesvirus saimiri, HVS and Herpesvirus ateles, HVA), which cause no or minor disease in their natural hosts, induce lymphomas or lymphoblastic leukemias in other primate species. The immune response of the natural host species to HVS is greater than that of animals developing malignancies after experimental infection. HVS and HVA share many properties with Epstein-Barr virus (EBV) of man, including antigens appearing early and late during infection and their related antibody responses but no evidence exists that they induce malignancies in their natural hosts. However, if induction is as infrequent as that with EBV and Burkitt's lymphoma (BL), we have not observed sufficient numbers of squirrel or spider monkeys to have seen a BL-like tumor. Interference with the immune systems of animals carrying HVS or HVA may induce tumor development, and clarify our understanding of the relationships between EBV and BL."} {"id": "PMID:169834", "title": "Horizontal transmission of feline leukemia virus in cats.", "content": "Traditionally, cancer has not been considered an infectious disease although some multiple cases of leukemia in man and cattle have been reported. The discovery that feline lymphosarcoma was associated with an RNA virus (feline leukemia virus(FeLV)) meant that infectious transmission of the disease was a possibility. The critical question was whether the predominant method of transmission from one animal to another was 'vertical' (via the gametes) or 'horizontal' (via contagion or infection). A number of epidemiological studies have shown that the chances of healthy cats contracting lymphosarcoma are greatly increased when a cat with the disease lives in close proximity. It does not matter whether the healthy cats are related to the sick animal or not. It has also been established that viremic normal cats have an approximately 900 times greater chance of developing leukemia than cats whose FeLV status is unknown. Infectious FeLV is present in the excretions and blood of viremic animals. In the natural environment, feline lymphosarcoma occurs in clusters. The results in pet cats have been supported by experiments with cat colonies under controlled conditions and prove that horizontal transmission of FeLV occurs. This does not mean that epigenetic (infection in utero or via the milk) or vertical transmission cannot also occur. It should be possible to break the cycle of horizontal transmission of the virus by vaccination and thus control FeLV-related diseases.", "contents": "Horizontal transmission of feline leukemia virus in cats. Traditionally, cancer has not been considered an infectious disease although some multiple cases of leukemia in man and cattle have been reported. The discovery that feline lymphosarcoma was associated with an RNA virus (feline leukemia virus(FeLV)) meant that infectious transmission of the disease was a possibility. The critical question was whether the predominant method of transmission from one animal to another was 'vertical' (via the gametes) or 'horizontal' (via contagion or infection). A number of epidemiological studies have shown that the chances of healthy cats contracting lymphosarcoma are greatly increased when a cat with the disease lives in close proximity. It does not matter whether the healthy cats are related to the sick animal or not. It has also been established that viremic normal cats have an approximately 900 times greater chance of developing leukemia than cats whose FeLV status is unknown. Infectious FeLV is present in the excretions and blood of viremic animals. In the natural environment, feline lymphosarcoma occurs in clusters. The results in pet cats have been supported by experiments with cat colonies under controlled conditions and prove that horizontal transmission of FeLV occurs. This does not mean that epigenetic (infection in utero or via the milk) or vertical transmission cannot also occur. It should be possible to break the cycle of horizontal transmission of the virus by vaccination and thus control FeLV-related diseases."} {"id": "PMID:169835", "title": "Cytocidal action of anticancer antigens: evaluation of the sensitivity of cultured animal and human cancer cells.", "content": "The cultured cell lines Yoshida ascites sarcoma, L-1210 mouse leukemia, OAT cell line derived from human lung cancer of the oat cell type, and P3HR-1 cell line derived from Burkitt's lymphoma have been used for the cell-killing kinetics study of anticancer agents and evaluation of the sensitivity of cells using the soft agar cloning assay method. It has been found that there are 2 types of actions: 1) Type I (cytocidal and concentration-dependent action). The dose survival curves of Type I agents fit the equation log S=log nminuskD (S, surviving fraction; D, concentration of agents; n and k are constant). The sensitivity of cells can be expressed by mean lethal dose 90% (MLD90=1/k). Four cell lines were compared on this basis, and some problems concerning the chemotherapy of human cancer are discussed. Alkylating agents and anticancer antibiotics belonged to this group.2) Type II (cytostatic and time-dependent action). The dose survival curves fit the Gompertz equation S=exp[(minusbeta/alpha)(1minus e-aD)] (beta, population reduction parameter; alpha, constant). The exposure survival curve is negative exponential, indicating that exposure time rather than concentration is the key fo effective cell killing of Type II agents. Difficulties in expression of sensitivity to Type II agents are discussed. Antimetabolites, Vinca alkaloids, and L-asparaginase belonged to this group. The cell-killing kinetics of anticancer agents and comparison of the sensitivity of cells may provide some indications not only of optimal dosage schedules but also of a new approach in screening systems for truly effective agents for human cancer.", "contents": "Cytocidal action of anticancer antigens: evaluation of the sensitivity of cultured animal and human cancer cells. The cultured cell lines Yoshida ascites sarcoma, L-1210 mouse leukemia, OAT cell line derived from human lung cancer of the oat cell type, and P3HR-1 cell line derived from Burkitt's lymphoma have been used for the cell-killing kinetics study of anticancer agents and evaluation of the sensitivity of cells using the soft agar cloning assay method. It has been found that there are 2 types of actions: 1) Type I (cytocidal and concentration-dependent action). The dose survival curves of Type I agents fit the equation log S=log nminuskD (S, surviving fraction; D, concentration of agents; n and k are constant). The sensitivity of cells can be expressed by mean lethal dose 90% (MLD90=1/k). Four cell lines were compared on this basis, and some problems concerning the chemotherapy of human cancer are discussed. Alkylating agents and anticancer antibiotics belonged to this group.2) Type II (cytostatic and time-dependent action). The dose survival curves fit the Gompertz equation S=exp[(minusbeta/alpha)(1minus e-aD)] (beta, population reduction parameter; alpha, constant). The exposure survival curve is negative exponential, indicating that exposure time rather than concentration is the key fo effective cell killing of Type II agents. Difficulties in expression of sensitivity to Type II agents are discussed. Antimetabolites, Vinca alkaloids, and L-asparaginase belonged to this group. The cell-killing kinetics of anticancer agents and comparison of the sensitivity of cells may provide some indications not only of optimal dosage schedules but also of a new approach in screening systems for truly effective agents for human cancer."} {"id": "PMID:169836", "title": "Nonhuman primate models for lymphoma, leukemia, and other neoplasms.", "content": "Herpesvirus saimiri (HVS) is an oncogenic virus for a variety of nonhuman primates. HVS does not produce overt disease upon inoculation in the natural host (squirrel monkey) but consistently induces neoplasms including lymphomas and lymphocytic leukemias in 4 other species of monkeys. Various drugs inhibit replication of HVS in vitro including cytosine arabinoside and adenine arabinoside. In addition, the lymphoma and leukemia induced in owl monkeys responds to vincristine and prednisolone, cyclophosphamide, cytosine arabinoside, and human interferon. Of the various chemical carcinogens studied, the antitumor agent procarbazine induces neoplasms in a variety of species including monkeys. Thus far this compound has induced acute myelogenous leukemia (AML), lymphoma, and hemangiosarcomas in macaques. We have induced primary liver tumors in macaques with several nitrosamines and aflatoxin B1 and these tumors produce alpha-fetoprotein (AFP) which can be assayed for both diagnosis and therapy. Thus far, therapy of hepatocellular carcinoma has been most successful with surgical resection; and the tumor mass and serum AFP have been less responsive to single agent chemotherapy. These nonhuman primate models are useful for an understanding of the cause, diagnosis, prevention, and treatment of the human disease.", "contents": "Nonhuman primate models for lymphoma, leukemia, and other neoplasms. Herpesvirus saimiri (HVS) is an oncogenic virus for a variety of nonhuman primates. HVS does not produce overt disease upon inoculation in the natural host (squirrel monkey) but consistently induces neoplasms including lymphomas and lymphocytic leukemias in 4 other species of monkeys. Various drugs inhibit replication of HVS in vitro including cytosine arabinoside and adenine arabinoside. In addition, the lymphoma and leukemia induced in owl monkeys responds to vincristine and prednisolone, cyclophosphamide, cytosine arabinoside, and human interferon. Of the various chemical carcinogens studied, the antitumor agent procarbazine induces neoplasms in a variety of species including monkeys. Thus far this compound has induced acute myelogenous leukemia (AML), lymphoma, and hemangiosarcomas in macaques. We have induced primary liver tumors in macaques with several nitrosamines and aflatoxin B1 and these tumors produce alpha-fetoprotein (AFP) which can be assayed for both diagnosis and therapy. Thus far, therapy of hepatocellular carcinoma has been most successful with surgical resection; and the tumor mass and serum AFP have been less responsive to single agent chemotherapy. These nonhuman primate models are useful for an understanding of the cause, diagnosis, prevention, and treatment of the human disease."} {"id": "PMID:169837", "title": "Biohazards and simian viruses.", "content": "Nonhuman primates are extensively used in laboratories as experimental animals. It is necessary, however, to realize that their employment may be dangerous to man and other species of primates, if recognition of their flora and fauna, especially viral, is not considered and if appropriate controls are not followed. Several outbreaks have occurred, resulting in high mortality and morbidity of man and simian. A number of recommendations are provided which, if followed, will minimize the waste of time, money, and life.", "contents": "Biohazards and simian viruses. Nonhuman primates are extensively used in laboratories as experimental animals. It is necessary, however, to realize that their employment may be dangerous to man and other species of primates, if recognition of their flora and fauna, especially viral, is not considered and if appropriate controls are not followed. Several outbreaks have occurred, resulting in high mortality and morbidity of man and simian. A number of recommendations are provided which, if followed, will minimize the waste of time, money, and life."} {"id": "PMID:169838", "title": "In vitro transformation of cells from human neoplasms.", "content": "The possible involvement of RNA tumor virus genomes in human cell transformation was investigated. Forty-nine cell cultures from neoplastic, normal, or embryo tissues were examined for transformation, following inoculation of murine leukemia virus (MuLV), feline leukemia virus (FeLV) grown in human cells, or bone marrow aspirates from leukemia patients. Five cultures exhibited transformation (1 after inoculation of MuLV grown in human cells; 4 after inoculation of human leukemic bone marrow), and 4 were established as cell lines. They were derived from giant cell tumor and fibrosarcomas. The established transformed cells formed colonies in soft agar, grew progressively in immunosuppressed mice, and carried antigens common to FeLV and MuLV. Although virus particles were not seen in these cultures, 68S RNA was detected in their media. Medium from nontransformed parent cultures also contained 68S RNA but in amounts about 15 times less than in transformed cultures. Transformed human cells passaged in mice produced both type C virus particles and 68S RNA. Antigens common to MuLV and FeLV were found in these particles. However, the results of biological and serological studies indicate their difference from conventional MuLV and FeLV. The relationship of this virus and 68S RNA found in transformed cultures remains to be determined.", "contents": "In vitro transformation of cells from human neoplasms. The possible involvement of RNA tumor virus genomes in human cell transformation was investigated. Forty-nine cell cultures from neoplastic, normal, or embryo tissues were examined for transformation, following inoculation of murine leukemia virus (MuLV), feline leukemia virus (FeLV) grown in human cells, or bone marrow aspirates from leukemia patients. Five cultures exhibited transformation (1 after inoculation of MuLV grown in human cells; 4 after inoculation of human leukemic bone marrow), and 4 were established as cell lines. They were derived from giant cell tumor and fibrosarcomas. The established transformed cells formed colonies in soft agar, grew progressively in immunosuppressed mice, and carried antigens common to FeLV and MuLV. Although virus particles were not seen in these cultures, 68S RNA was detected in their media. Medium from nontransformed parent cultures also contained 68S RNA but in amounts about 15 times less than in transformed cultures. Transformed human cells passaged in mice produced both type C virus particles and 68S RNA. Antigens common to MuLV and FeLV were found in these particles. However, the results of biological and serological studies indicate their difference from conventional MuLV and FeLV. The relationship of this virus and 68S RNA found in transformed cultures remains to be determined."} {"id": "PMID:169854", "title": "[Liver damage caused by laxatives. A contribution to the hepatotoxicity of 4,4'-(2-quinolylmethylene)-diphenol-hydrochloride].", "content": "A female patient developed a recurrent hepatitis-like liver damage after ingestion of a laxative containing 4,4'-(2-quinolyl-methylene)-diphenol-hydrochloride. After cessation of the drug the clinical picture improved. The hyperbilirubinemia decreased and the definitely elevated GOT, GPT, alkaline phosphatase and gamma-GTP became normal. Histologically hepato-cellular damage was seen with intra-hepatic cholestasis. As a cause for these symptoms, resembling those after taking oxyphenisatin-containing preparations, immunological procedures were thought responsible, such as \"unpredictable hepatic drug reactions\".", "contents": "[Liver damage caused by laxatives. A contribution to the hepatotoxicity of 4,4'-(2-quinolylmethylene)-diphenol-hydrochloride]. A female patient developed a recurrent hepatitis-like liver damage after ingestion of a laxative containing 4,4'-(2-quinolyl-methylene)-diphenol-hydrochloride. After cessation of the drug the clinical picture improved. The hyperbilirubinemia decreased and the definitely elevated GOT, GPT, alkaline phosphatase and gamma-GTP became normal. Histologically hepato-cellular damage was seen with intra-hepatic cholestasis. As a cause for these symptoms, resembling those after taking oxyphenisatin-containing preparations, immunological procedures were thought responsible, such as \"unpredictable hepatic drug reactions\"."} {"id": "PMID:169856", "title": "Metabolism of D- and L-norgestrel in humans.", "content": "Levels of DL-norgestrel, D-norgestrel, L-norgestrel and norethisterone were measured in blood by radioimmunoassay after oral administration of the progestin to 3 healthy male subjects and the half-lives calculated. Half-lives for D-norgestrel were much lower than those of L-norgestrel and similar to those of norethisterone. Measurement of norgestrel in blood can therefore be misleading unless the biologically active D-isomer is estimated. Since there was no difference in half-lives between norgestrel and norethisterone the greater potency of the former is probably due to it more strongly binding to target organ receptors.", "contents": "Metabolism of D- and L-norgestrel in humans. Levels of DL-norgestrel, D-norgestrel, L-norgestrel and norethisterone were measured in blood by radioimmunoassay after oral administration of the progestin to 3 healthy male subjects and the half-lives calculated. Half-lives for D-norgestrel were much lower than those of L-norgestrel and similar to those of norethisterone. Measurement of norgestrel in blood can therefore be misleading unless the biologically active D-isomer is estimated. Since there was no difference in half-lives between norgestrel and norethisterone the greater potency of the former is probably due to it more strongly binding to target organ receptors."} {"id": "PMID:169861", "title": "Methanol extraction residue of BCG in the treatment of transplanted rat tumours.", "content": "Subcutaneous growth of immunogenic chemically induced rat sarcomata and a hepatoma was restricted when cells were injected into syngeneic animals in admixture with MER. Rats rejecting mixed inocula were immune to further challenge with the same tumour. Growth of a chemically induced mammary carcinoma which lacks detectable immunogenicity was suppressed when low cell inocula were injected in admixture with MER or intact BCG organisms, although animals were not immune to re-challenge. These studies indicate that clinically MER may be a suitable alternative to BCG for contact suppression of tumour growth or incorporation into tumour cell:adjuvant vaccines for active immunotherapy.", "contents": "Methanol extraction residue of BCG in the treatment of transplanted rat tumours. Subcutaneous growth of immunogenic chemically induced rat sarcomata and a hepatoma was restricted when cells were injected into syngeneic animals in admixture with MER. Rats rejecting mixed inocula were immune to further challenge with the same tumour. Growth of a chemically induced mammary carcinoma which lacks detectable immunogenicity was suppressed when low cell inocula were injected in admixture with MER or intact BCG organisms, although animals were not immune to re-challenge. These studies indicate that clinically MER may be a suitable alternative to BCG for contact suppression of tumour growth or incorporation into tumour cell:adjuvant vaccines for active immunotherapy."} {"id": "PMID:169862", "title": "An electron microscopic study of tumour cell adhesiveness induced by aggregation promoting factor from rat ascites hepatoma cells.", "content": "A substance capable of inducing tumour cell aggregation, which is supposed to be a glycoprotein showing noncytotoxicity, was separated from rat ascites hepatoma cells and partially purified by chromatography. Adhesiveness of rat ascites hepatoma cells induced by this substance was characterized by gradual development of known binding structures during a period of 24 h after contact with the substance; simple apposition and intermediate junctions developed in the early stage, and desmosomes and focal tight junctions in the later stage. It was assumed that the substance might be involved in the development of such binding structures as a triggering mechanism of tumour cell adhesiveness.", "contents": "An electron microscopic study of tumour cell adhesiveness induced by aggregation promoting factor from rat ascites hepatoma cells. A substance capable of inducing tumour cell aggregation, which is supposed to be a glycoprotein showing noncytotoxicity, was separated from rat ascites hepatoma cells and partially purified by chromatography. Adhesiveness of rat ascites hepatoma cells induced by this substance was characterized by gradual development of known binding structures during a period of 24 h after contact with the substance; simple apposition and intermediate junctions developed in the early stage, and desmosomes and focal tight junctions in the later stage. It was assumed that the substance might be involved in the development of such binding structures as a triggering mechanism of tumour cell adhesiveness."} {"id": "PMID:169865", "title": "Inappropriate production of collagen and prolyl hydroxylase by human breast cancer cells in vivo.", "content": "Thirty-two scirrhous cancers of breast have been examined to determine the origin of the collagen stroma in these tumours. Employing two immunohistochemical techniques it has been shown that the malignant epithelial cells in 30 of these tumours contain not only collagen but also prolyl hydroxylase, a key enzyme in collagen biosynthesis. Neither this enzyme nor collagen was detectable in the spindle cells in the stroma of these tumours. Neither the epithelium in normal breast, that in fibrocystic disease and in fibroadenomata, nor the malignant epithelium in two medullary cancers of breast contained either collagen or prolyl hydroxylase. These results strongly suggest that the malignant epithelium of scirrhous breast cancers produces its own collagen stroma and that the scirrhous reaction in these tumours is not a host response to tumour invasion. The production of collagen and prolyl hydroxylase by breast cancer cells (of the scirrhous type) therefore represents another example of inappropriate protein production by a human tumour.", "contents": "Inappropriate production of collagen and prolyl hydroxylase by human breast cancer cells in vivo. Thirty-two scirrhous cancers of breast have been examined to determine the origin of the collagen stroma in these tumours. Employing two immunohistochemical techniques it has been shown that the malignant epithelial cells in 30 of these tumours contain not only collagen but also prolyl hydroxylase, a key enzyme in collagen biosynthesis. Neither this enzyme nor collagen was detectable in the spindle cells in the stroma of these tumours. Neither the epithelium in normal breast, that in fibrocystic disease and in fibroadenomata, nor the malignant epithelium in two medullary cancers of breast contained either collagen or prolyl hydroxylase. These results strongly suggest that the malignant epithelium of scirrhous breast cancers produces its own collagen stroma and that the scirrhous reaction in these tumours is not a host response to tumour invasion. The production of collagen and prolyl hydroxylase by breast cancer cells (of the scirrhous type) therefore represents another example of inappropriate protein production by a human tumour."} {"id": "PMID:169866", "title": "Electron spin resonance study of changes during the development of a mouse myeloid leukaemia. I. Paramagnetic metal ions.", "content": "The blood, spleen and liver of mice were examined by means of electron spin resonance (e.s.r.), throughout the course of myeloid leukaemia induced by intravenous injection of leukaemic spleen cells. In blood, marked increases in the concentrations of iron transferrin and ceruloplasmin occurred within the first 3 days after injection. In the spleen, changes in the concentrations of paramagnetic copper and iron complexes were detectable by about the 5th day, before any measurable splenic enlargement, whilst in the liver changes were detectable by about the 8th day. The changes occurring in blood, spleen and liver during the development of leukaemia appear to be related and they are discussed in terms of iron transport.", "contents": "Electron spin resonance study of changes during the development of a mouse myeloid leukaemia. I. Paramagnetic metal ions. The blood, spleen and liver of mice were examined by means of electron spin resonance (e.s.r.), throughout the course of myeloid leukaemia induced by intravenous injection of leukaemic spleen cells. In blood, marked increases in the concentrations of iron transferrin and ceruloplasmin occurred within the first 3 days after injection. In the spleen, changes in the concentrations of paramagnetic copper and iron complexes were detectable by about the 5th day, before any measurable splenic enlargement, whilst in the liver changes were detectable by about the 8th day. The changes occurring in blood, spleen and liver during the development of leukaemia appear to be related and they are discussed in terms of iron transport."} {"id": "PMID:169867", "title": "Loss of anti-tumour immunogenicity of a somatic cell hybrid line with increasing subculture.", "content": "Good immunoprotection was afforded by A9/SEWA somatic hybrid cells in the C3H mouse/C3H Py tumour system, confirming results previously obtained in the A.SW mouse/SEWA tumour system. However, in this study the immunogenicity decreased with increasing serial subculture of the hybrid line and concomitant chromosome loss.", "contents": "Loss of anti-tumour immunogenicity of a somatic cell hybrid line with increasing subculture. Good immunoprotection was afforded by A9/SEWA somatic hybrid cells in the C3H mouse/C3H Py tumour system, confirming results previously obtained in the A.SW mouse/SEWA tumour system. However, in this study the immunogenicity decreased with increasing serial subculture of the hybrid line and concomitant chromosome loss."} {"id": "PMID:169868", "title": "Serum antibody responses to an ascitic variant of rat hepatoma D23.", "content": "Antibody was detected by membrane immunofluorescence tests in sera of rats bearing an ascitic variant of a transplanted hepatoma, and in concentrated cell-free ascitic fluid. Ascites hepatoma cells were also shown to have immunoglobulin, possibly tumour specific antibody, bound to their surface. The kinetics of antibody responses to ascites hepatoma and hepatoma cells from solid tumours were compared: both tumour types gave positive reactions by the third day after implantation; antibody was present throughout subsequent tumour growth with the ascites whereas antibody was not detected after tumour became palpable in rats injected with hepatoma cells from solid tumour. Antibody responses to ascites tumour were investigated in rats bearing solid hepatoma tumour. Subcutaneous hepatoma did not influence the antibody response to ascites, but rats bearing intraperitoneal tumours showed a diminished serum antibody response to ascitic hepatoma.", "contents": "Serum antibody responses to an ascitic variant of rat hepatoma D23. Antibody was detected by membrane immunofluorescence tests in sera of rats bearing an ascitic variant of a transplanted hepatoma, and in concentrated cell-free ascitic fluid. Ascites hepatoma cells were also shown to have immunoglobulin, possibly tumour specific antibody, bound to their surface. The kinetics of antibody responses to ascites hepatoma and hepatoma cells from solid tumours were compared: both tumour types gave positive reactions by the third day after implantation; antibody was present throughout subsequent tumour growth with the ascites whereas antibody was not detected after tumour became palpable in rats injected with hepatoma cells from solid tumour. Antibody responses to ascites tumour were investigated in rats bearing solid hepatoma tumour. Subcutaneous hepatoma did not influence the antibody response to ascites, but rats bearing intraperitoneal tumours showed a diminished serum antibody response to ascitic hepatoma."} {"id": "PMID:169869", "title": "Effects of 5-fluorouracil on the cell kinetic and growth parameters of hepatoma 3924A.", "content": "The effect of 5-fluorouracil (5-FU) on the growth and cellular proliferation of hepatoma 3924A was studied using the following parameters as indices of tumour response: (1) volume measurements, (2) cell kinetic analysis including estimates of both growth and cell loss fractions, (3) changes in tumour histology and (4) tumour DNA content and DNA synthesis. Of a series of single intraperitoneally injected doses (25-300 mg/kg body weight), 150 mg/kg interrupted tumour growth most effectively with minimal toxicity within 168 h, and after 10 days treated tumour volumes were only 42% of untreated tumour size. Doses of 25 mg/kg failed to change the rate of growth while 300 mg/kg exceeded the LD50. Alterations of both tumour cell proliferation and histology developed well in advance of changes observed in growth. A dose of 150 mg/kg body weight blocked the transition of cells from G1 through S for a 24 h interval when cell kinetics were measured by 3H-TdR autoradiography. However, 3H-UdR incorporation into DNA following 5-FU suggested that cellular recovery from the drug was delayed for an additional 24 h. Concurrently, significant losses of tumour tissue and tumour DNA occurred during the first 48 h with an expected increase in both necrotic and connective tissue. During the subsequent 120 h both tumour and necrotic tissue had returned to non-treated levels, while kinetic analysis revealed (a) a slight reduction in the cell cycle time and growth fraction and (b) an increased cell loss factor. The observations from this tumour model system suggest that before using tumour volume or weight as an index of therapeutic response, the relationship between the kinetics of tumour cellularity and tumour volume must be defined.", "contents": "Effects of 5-fluorouracil on the cell kinetic and growth parameters of hepatoma 3924A. The effect of 5-fluorouracil (5-FU) on the growth and cellular proliferation of hepatoma 3924A was studied using the following parameters as indices of tumour response: (1) volume measurements, (2) cell kinetic analysis including estimates of both growth and cell loss fractions, (3) changes in tumour histology and (4) tumour DNA content and DNA synthesis. Of a series of single intraperitoneally injected doses (25-300 mg/kg body weight), 150 mg/kg interrupted tumour growth most effectively with minimal toxicity within 168 h, and after 10 days treated tumour volumes were only 42% of untreated tumour size. Doses of 25 mg/kg failed to change the rate of growth while 300 mg/kg exceeded the LD50. Alterations of both tumour cell proliferation and histology developed well in advance of changes observed in growth. A dose of 150 mg/kg body weight blocked the transition of cells from G1 through S for a 24 h interval when cell kinetics were measured by 3H-TdR autoradiography. However, 3H-UdR incorporation into DNA following 5-FU suggested that cellular recovery from the drug was delayed for an additional 24 h. Concurrently, significant losses of tumour tissue and tumour DNA occurred during the first 48 h with an expected increase in both necrotic and connective tissue. During the subsequent 120 h both tumour and necrotic tissue had returned to non-treated levels, while kinetic analysis revealed (a) a slight reduction in the cell cycle time and growth fraction and (b) an increased cell loss factor. The observations from this tumour model system suggest that before using tumour volume or weight as an index of therapeutic response, the relationship between the kinetics of tumour cellularity and tumour volume must be defined."} {"id": "PMID:169870", "title": "A new method for monitoring subclinical virus infections of the central nervous system in mice.", "content": "The course of a subclinical virus infection of the central nervous system (CNS) of mice has been followed by measuring spontaneous motor activity using Animex equipment. A significant drop in activity occurred on the 5th and 6th day after inoculation with the A774 (avirulent) strain of Semliki Forest virus (SFV) before histological changes were apparent but at the same time as maximum brain virus titre. The relationship of the fall in activity to changes in the pattern of weight gain, food and water intake was also investigated.", "contents": "A new method for monitoring subclinical virus infections of the central nervous system in mice. The course of a subclinical virus infection of the central nervous system (CNS) of mice has been followed by measuring spontaneous motor activity using Animex equipment. A significant drop in activity occurred on the 5th and 6th day after inoculation with the A774 (avirulent) strain of Semliki Forest virus (SFV) before histological changes were apparent but at the same time as maximum brain virus titre. The relationship of the fall in activity to changes in the pattern of weight gain, food and water intake was also investigated."} {"id": "PMID:169871", "title": "Morphological and virological investigations of cell strains cultured from the brain in Jakob-Creutzfeldt disease and subacute sclerosing panencephalitis.", "content": "Cell strains were established in culture from fragments of the brain from 2 cases each of Jakob-Creutzfeldt (JC) disease and subacute sclerosing panencephalitis (SSPE). After about 12 weeks strains from the former spontaneously formed persistent heaped up nodules of cells which appeared to produce reticulin-like fibrils as well as confluent sheets of rounded and spindle, fibroblast-like cells. Similar sheets of cells were obtained from the cases of SSPE but the only nodules formed were smaller and ephemeral. Attempts to detect virus in all 4 strains were made by inoculation of supernatant fluids into cultures of other laboratory cells, haemadsorption, co-cultivation, electron microscopy and immunofluorescence, and testing for interferon production. No evidence was found by any of these methods of the persistent presence of virus in the strains. Immunofluorescence revealed a probable anti-glial cell IgM autoantibody in one case of JC disease. Morphologically some cells resembled astrocytes and others fibroblasts. Those from JC disease contained more vacuoles and redundant membranes than did those from the cases of SSPE, features that are particularly striking in brain cells in human and animal cases of the spongiform encephalopathies.", "contents": "Morphological and virological investigations of cell strains cultured from the brain in Jakob-Creutzfeldt disease and subacute sclerosing panencephalitis. Cell strains were established in culture from fragments of the brain from 2 cases each of Jakob-Creutzfeldt (JC) disease and subacute sclerosing panencephalitis (SSPE). After about 12 weeks strains from the former spontaneously formed persistent heaped up nodules of cells which appeared to produce reticulin-like fibrils as well as confluent sheets of rounded and spindle, fibroblast-like cells. Similar sheets of cells were obtained from the cases of SSPE but the only nodules formed were smaller and ephemeral. Attempts to detect virus in all 4 strains were made by inoculation of supernatant fluids into cultures of other laboratory cells, haemadsorption, co-cultivation, electron microscopy and immunofluorescence, and testing for interferon production. No evidence was found by any of these methods of the persistent presence of virus in the strains. Immunofluorescence revealed a probable anti-glial cell IgM autoantibody in one case of JC disease. Morphologically some cells resembled astrocytes and others fibroblasts. Those from JC disease contained more vacuoles and redundant membranes than did those from the cases of SSPE, features that are particularly striking in brain cells in human and animal cases of the spongiform encephalopathies."} {"id": "PMID:169872", "title": "Hypersensitive and insensitive extremities. The dermatological aspects.", "content": "The importance of physically intact hands and feet is taken for granted and consequently not appreciated until they are functionally impaired by vascular or neural injury of disease. The pathogenesis and clinical manifestations of cutaneous lesions complicating hypersensitive and insensitive limbs are described. The current therapeutic approaches and measures for these conditions are presented. Protection and prophylaxis trauma for neurologically impaired parts are emphasized.", "contents": "Hypersensitive and insensitive extremities. The dermatological aspects. The importance of physically intact hands and feet is taken for granted and consequently not appreciated until they are functionally impaired by vascular or neural injury of disease. The pathogenesis and clinical manifestations of cutaneous lesions complicating hypersensitive and insensitive limbs are described. The current therapeutic approaches and measures for these conditions are presented. Protection and prophylaxis trauma for neurologically impaired parts are emphasized."} {"id": "PMID:169873", "title": "Intraendothelial tubular aggregates in experimental wounds.", "content": "Intraendothelial tubular aggregates were found in small dermal blood vessels in three healing superficial wounds in patients receiving systemic corticosteroids. Similar inclusions were also demonstrated in two wounds in healthy subjects, but were not found in normal (unwounded) skin of either healthy subjects or steroid-treated patients. Tubular aggregates of similar structure have previously been described as occurring in 'connective tissue' or 'auto-immune' diseases, including lupus erythematosus and dermatomyositis, both in the skin and in internal organs. Although it has been suggested that such aggregates are of viral origin, their morphogenesis and significance remain undertermined. Our findings do not support a viral cause, but suggest that these structures are probably a product of regenerating endothelium.", "contents": "Intraendothelial tubular aggregates in experimental wounds. Intraendothelial tubular aggregates were found in small dermal blood vessels in three healing superficial wounds in patients receiving systemic corticosteroids. Similar inclusions were also demonstrated in two wounds in healthy subjects, but were not found in normal (unwounded) skin of either healthy subjects or steroid-treated patients. Tubular aggregates of similar structure have previously been described as occurring in 'connective tissue' or 'auto-immune' diseases, including lupus erythematosus and dermatomyositis, both in the skin and in internal organs. Although it has been suggested that such aggregates are of viral origin, their morphogenesis and significance remain undertermined. Our findings do not support a viral cause, but suggest that these structures are probably a product of regenerating endothelium."} {"id": "PMID:169874", "title": "Generalized bullous and haemorrhagic lichen sclerosus et atrophicus. Marked improvement with ACTH.", "content": "An unusual case of lichen sclerosus et atrophicus is described, in which lesions were bullous and haemorrhagic and extended over almost the entire surface of the skin. A marked improvement followed treatment with ACTH.", "contents": "Generalized bullous and haemorrhagic lichen sclerosus et atrophicus. Marked improvement with ACTH. An unusual case of lichen sclerosus et atrophicus is described, in which lesions were bullous and haemorrhagic and extended over almost the entire surface of the skin. A marked improvement followed treatment with ACTH."} {"id": "PMID:169875", "title": "Radiography in functional lacrimal testing.", "content": "A functional study of the lacrimal drainage apparatus was made in 25 patients. Angiographin was instilled into the conjunctival sac and serial radiographs were taken. The films were interpreted in conjunction with the intubation macro-dacryocystograms. Although this is a useful procedure, the use of angiographin compares unfavourably with ultra-fluid Lipiodol in a similar procedure.", "contents": "Radiography in functional lacrimal testing. A functional study of the lacrimal drainage apparatus was made in 25 patients. Angiographin was instilled into the conjunctival sac and serial radiographs were taken. The films were interpreted in conjunction with the intubation macro-dacryocystograms. Although this is a useful procedure, the use of angiographin compares unfavourably with ultra-fluid Lipiodol in a similar procedure."} {"id": "PMID:169876", "title": "Homonymous hemianopia in multiple sclerosis. With report of bilateral case.", "content": "A patient with multiple sclerosis and bilateral retrochiasmal visual field defects is reported. Homonymous field defects are rare in multiple sclerosis despite the frequency of pathological involvement of the retrochiasmal visual pathways. A higher incidence might be found with a higher index of suspicion and careful visual field testing with qualitative confrontation technique. Other reasons for the infrequent clinical detection of retrochiasmal lesions are considered. Such lesions may exist without demonstrable defect. This may be explained by anatomical factors, for example, fibre arrangement, or physiological factors, such as, geniculate or retrogeniculate integration. Lesions producing demonstrable defects may be asymptomatic because they: affect only the peripheral field, are small scotomas that do not impair visual acuity, affect only one eye, or occur late in the course of disease when masked by optic nerve involvement.", "contents": "Homonymous hemianopia in multiple sclerosis. With report of bilateral case. A patient with multiple sclerosis and bilateral retrochiasmal visual field defects is reported. Homonymous field defects are rare in multiple sclerosis despite the frequency of pathological involvement of the retrochiasmal visual pathways. A higher incidence might be found with a higher index of suspicion and careful visual field testing with qualitative confrontation technique. Other reasons for the infrequent clinical detection of retrochiasmal lesions are considered. Such lesions may exist without demonstrable defect. This may be explained by anatomical factors, for example, fibre arrangement, or physiological factors, such as, geniculate or retrogeniculate integration. Lesions producing demonstrable defects may be asymptomatic because they: affect only the peripheral field, are small scotomas that do not impair visual acuity, affect only one eye, or occur late in the course of disease when masked by optic nerve involvement."} {"id": "PMID:169877", "title": "Collagenase and other proteinases in the cornea of the retinol-deficient rat.", "content": "1. Enzymes that may contribute to liquefaction of the cornea in retinol-deficient animals and in man have been studied using rat cornea. The established technique of culturing tissue fragments and determining the activity of collagenase (EC 3-4-24-3) and other enzymes in the medium after different periods of culture was used. 2. A collagenolytic system was detected in the media from cultures of rat corneas. This system probably consists of at least two enzymes, a collagenase and a neutral proteinase. 3. Both proteolytic and specific collagenolytic activity were greater in media from retinol-deficient rat corneas. The hydroxyproline level increased in parallel with the increase in enzyme activity. 4. In the final stages of retinol deficiency the cornea is invaded by granulocytes and other cells of the blood and we suggest that destruction of cornea collagen may be due largely to the activity of the enzymes from these cells.", "contents": "Collagenase and other proteinases in the cornea of the retinol-deficient rat. 1. Enzymes that may contribute to liquefaction of the cornea in retinol-deficient animals and in man have been studied using rat cornea. The established technique of culturing tissue fragments and determining the activity of collagenase (EC 3-4-24-3) and other enzymes in the medium after different periods of culture was used. 2. A collagenolytic system was detected in the media from cultures of rat corneas. This system probably consists of at least two enzymes, a collagenase and a neutral proteinase. 3. Both proteolytic and specific collagenolytic activity were greater in media from retinol-deficient rat corneas. The hydroxyproline level increased in parallel with the increase in enzyme activity. 4. In the final stages of retinol deficiency the cornea is invaded by granulocytes and other cells of the blood and we suggest that destruction of cornea collagen may be due largely to the activity of the enzymes from these cells."} {"id": "PMID:169878", "title": "Conformational energy refinement of horse-heart ferricytochrome c.", "content": "The reported X-ray structure of horse-heart ferricytochrome c has been refined by conformational energy calculations, using a three-stage computational procedure. In stage I, the atomic positions are adjusted to conform to idealized bond lengths and bond angles characteristic of small amino acid derivatives, while yet remaining as close as possible to the X-ray coordinates. In stage II, atomic overlaps are eliminated by adjusting the backbone and side-chain dihedral angles to minimize the nonbonded energy, hydrogen-bonded energy, and rotational energy contributions. In the final stage of refinement, the electrostatic energy and a more accurate hydrogen-bonded energy treatment are considered, in addition to the energy contributions of stage II. A \"fitting potential\" of gradually decreasing strength is imposed in both stages II and III, in order to keep the computed structure as similar to the x-ray structure as is consistent with a low-energy conformation. The final computed structure of cytochrome c exhibits a very low conformational energy (-504 kcal/mol) and also closely resembles the X-ray structure (RMS deviation = 0.77 A for all atoms). However, a special treatment was required in order to alter the location of the phenyl ring of phenylalanine-82. In contrast to the originally published X-ray structure, which shows the phenyl ring pointing away from the heme, the phenyl ring in the computed structure is tucked into the heme crevice, in a position similar to that observed in the reduced form of tuna cytochrome c, in the oxidized form of Rhodospirillum rubrum cytochrome c2, and also in the recently determined structure of oxidized tuna cytochrome c.", "contents": "Conformational energy refinement of horse-heart ferricytochrome c. The reported X-ray structure of horse-heart ferricytochrome c has been refined by conformational energy calculations, using a three-stage computational procedure. In stage I, the atomic positions are adjusted to conform to idealized bond lengths and bond angles characteristic of small amino acid derivatives, while yet remaining as close as possible to the X-ray coordinates. In stage II, atomic overlaps are eliminated by adjusting the backbone and side-chain dihedral angles to minimize the nonbonded energy, hydrogen-bonded energy, and rotational energy contributions. In the final stage of refinement, the electrostatic energy and a more accurate hydrogen-bonded energy treatment are considered, in addition to the energy contributions of stage II. A \"fitting potential\" of gradually decreasing strength is imposed in both stages II and III, in order to keep the computed structure as similar to the x-ray structure as is consistent with a low-energy conformation. The final computed structure of cytochrome c exhibits a very low conformational energy (-504 kcal/mol) and also closely resembles the X-ray structure (RMS deviation = 0.77 A for all atoms). However, a special treatment was required in order to alter the location of the phenyl ring of phenylalanine-82. In contrast to the originally published X-ray structure, which shows the phenyl ring pointing away from the heme, the phenyl ring in the computed structure is tucked into the heme crevice, in a position similar to that observed in the reduced form of tuna cytochrome c, in the oxidized form of Rhodospirillum rubrum cytochrome c2, and also in the recently determined structure of oxidized tuna cytochrome c."} {"id": "PMID:169879", "title": "The influence of amino acid substitutions on the conformational energy of cytochrome c.", "content": "Conformational energies have been evaluated for each of the staggered side-chain conformations associated with the 261 amino acid substitutions known to occur among 60 eucaryotic species. At least 86% of these substitutions can be sterically accommodated (one at a time) within the structure of horse-heart cytochrome c resulting from conformational energy refinement. Simultaneous incorporation of all pertinent amino acid substitutions found in eight representative species into the refined horse-heart structure is also shown to be sterically possible, with few exceptions. In two cases (Pekin duck cytochrome with 10 substitutions and Samia cynthia cytochrome with 24 substitutions), all substitutions could be readily incorporated, and the total energies associated with their computed structures differed by less than 10 kcal/mol from that of horse-heart cytochrome c. In the cytochromes from rattlesnake (22 substitutions), tuna (18 substitutions), and Neurospora crassa (36 substitutions), tyrosine could not be substituted for phenylalanine at position 46, within the constraints of the calculations. However, when all of the remaining substitutions were incorporated into these three cytochromes, their computed conformational energies differed by less than 30 kcal/mol from that of horse-heart cytochrome c. Between two and four amino acid substitutions cause high energies in the cytochromes from human, baker's yeast, and cotton seed, but all of the remaining substitutions are consistent with a low energy conformation. These results suggest that the structures of homologous proteins may be even more similar than has previously been recognized. Substitutions of all possible amino acid types at the invariant positions (where all eucaryotic cytochromes c bear the same amino acid) have revealed some cases where different amino acids can be accommodated, thus demonstrating that the biological constraints on amino acid substitutions are often different from the purely steric constraints investigated in this work.", "contents": "The influence of amino acid substitutions on the conformational energy of cytochrome c. Conformational energies have been evaluated for each of the staggered side-chain conformations associated with the 261 amino acid substitutions known to occur among 60 eucaryotic species. At least 86% of these substitutions can be sterically accommodated (one at a time) within the structure of horse-heart cytochrome c resulting from conformational energy refinement. Simultaneous incorporation of all pertinent amino acid substitutions found in eight representative species into the refined horse-heart structure is also shown to be sterically possible, with few exceptions. In two cases (Pekin duck cytochrome with 10 substitutions and Samia cynthia cytochrome with 24 substitutions), all substitutions could be readily incorporated, and the total energies associated with their computed structures differed by less than 10 kcal/mol from that of horse-heart cytochrome c. In the cytochromes from rattlesnake (22 substitutions), tuna (18 substitutions), and Neurospora crassa (36 substitutions), tyrosine could not be substituted for phenylalanine at position 46, within the constraints of the calculations. However, when all of the remaining substitutions were incorporated into these three cytochromes, their computed conformational energies differed by less than 30 kcal/mol from that of horse-heart cytochrome c. Between two and four amino acid substitutions cause high energies in the cytochromes from human, baker's yeast, and cotton seed, but all of the remaining substitutions are consistent with a low energy conformation. These results suggest that the structures of homologous proteins may be even more similar than has previously been recognized. Substitutions of all possible amino acid types at the invariant positions (where all eucaryotic cytochromes c bear the same amino acid) have revealed some cases where different amino acids can be accommodated, thus demonstrating that the biological constraints on amino acid substitutions are often different from the purely steric constraints investigated in this work."} {"id": "PMID:169880", "title": "Cobalt-cytochrome c. I. Preparation, properties, and enzymic activity.", "content": "An improved procedure for the preparation of cobalt-cytochrome c has been developed. Various factors influencing the cobalt insertion process are discussed. The optical spectra of cobalt-cytochrome c suggest a six-coordinated species. The spectral shifts occurring with oxidation-reduction are compared with those observed for deoxy-cobaltohemoglobin and ferrocytochrome c and attributed to the effect of d(z2) electron on stereoelectronic interactions between the axial ligands and the porphyrin pi systems. Cobalt-cytochrome c has Em,7 = -140 +/- 20 mV as compared to an Em,7 of +250mV for ferrocytochrome c. An explanation for this negative Em,7 is offered. Cobaltocytochrome c is oxidized by cytochrome oxidase at about 45% of the rate for native cytochrome c. On the other hand cobalticytochrome c was not reduced by microsomal NADH or NADPH cytochrome c reductase nor by mitochondrial NADH or succinate cytochrome c reductase. It appears that the integrity of the reductase binding site is destroyed and the oxidase binding site has been modified by cobalt substitution.", "contents": "Cobalt-cytochrome c. I. Preparation, properties, and enzymic activity. An improved procedure for the preparation of cobalt-cytochrome c has been developed. Various factors influencing the cobalt insertion process are discussed. The optical spectra of cobalt-cytochrome c suggest a six-coordinated species. The spectral shifts occurring with oxidation-reduction are compared with those observed for deoxy-cobaltohemoglobin and ferrocytochrome c and attributed to the effect of d(z2) electron on stereoelectronic interactions between the axial ligands and the porphyrin pi systems. Cobalt-cytochrome c has Em,7 = -140 +/- 20 mV as compared to an Em,7 of +250mV for ferrocytochrome c. An explanation for this negative Em,7 is offered. Cobaltocytochrome c is oxidized by cytochrome oxidase at about 45% of the rate for native cytochrome c. On the other hand cobalticytochrome c was not reduced by microsomal NADH or NADPH cytochrome c reductase nor by mitochondrial NADH or succinate cytochrome c reductase. It appears that the integrity of the reductase binding site is destroyed and the oxidase binding site has been modified by cobalt substitution."} {"id": "PMID:169881", "title": "Controlled digestion with trypsin as a structural probe for the N-terminal peptide of soluble and membranous cytochrome c.", "content": "When purified bovine cytochrome c1 is digested with trypsin under controlled conditions, the heme polypeptide is preferentially converted from a species of molecular weight 30,600 to a heme polypeptide of molecular weight 29,000. The trypsin sensitive peptide bond is located in the N-terminal region of the cytochrome. Both the reduced and oxidized cytochrome are susceptible to hydrolysis by trypsin at the same locus, but the reduced cytochrome is cleaved at an initial rate approximately twofold greater than the oxidized cytochrome. Membranous cytochrome c1, as occurring in cytochrome b-c1 complex or succinate-cytochrome c reductase complex, is not susceptible to trypsin proteolysis under similar conditions, nor after more extensive treatment of the membranes with trypsin, in spite of the fact that cytochrome c1 presumably comes into contact with cytochrome c at the membrane surface during electron transport. These findings are consistent with a model for the structure of cytochrome c1 in situ in which the cytochrome is an integral membrane protein, located primarily in the membrane continuum, while still having the heme-containing portion of the protein available at the membrane surface for electron transfer to cytochrome c.", "contents": "Controlled digestion with trypsin as a structural probe for the N-terminal peptide of soluble and membranous cytochrome c. When purified bovine cytochrome c1 is digested with trypsin under controlled conditions, the heme polypeptide is preferentially converted from a species of molecular weight 30,600 to a heme polypeptide of molecular weight 29,000. The trypsin sensitive peptide bond is located in the N-terminal region of the cytochrome. Both the reduced and oxidized cytochrome are susceptible to hydrolysis by trypsin at the same locus, but the reduced cytochrome is cleaved at an initial rate approximately twofold greater than the oxidized cytochrome. Membranous cytochrome c1, as occurring in cytochrome b-c1 complex or succinate-cytochrome c reductase complex, is not susceptible to trypsin proteolysis under similar conditions, nor after more extensive treatment of the membranes with trypsin, in spite of the fact that cytochrome c1 presumably comes into contact with cytochrome c at the membrane surface during electron transport. These findings are consistent with a model for the structure of cytochrome c1 in situ in which the cytochrome is an integral membrane protein, located primarily in the membrane continuum, while still having the heme-containing portion of the protein available at the membrane surface for electron transfer to cytochrome c."} {"id": "PMID:169882", "title": "The specificity of induced conformational changes. The case of yeast glyceraldehyde-3-phosphate dehydrogenase.", "content": "The specificity of induced conformational changes and of the probes used to detect them has been investigated in yeast glyceraldehyde-3-phosphate dehydrogenase. Cyanylation of the active-site SH groups in two of the four identical subunits of glyceraldehyde-3-phosphate dehydrogenase has no effect on reactivity of the unmodified SH groups toward the cyanylating reagent (2-nitro-5-thiocyanogenzoic acid, NTCB) but results in total loss of catalytic activity. Cyanylation of the dicarboxamidomethylated enzyme was four orders of magnitude slower than with the unmodified enzyme in contrast to cyanylation of the dicyanylated enzyme. Cyanylation by NTCB as well as alkylation by iodoacetate and acylation with beta-(2-furyl)acryloyl phosphate are enhanced in the presence of NAD+ while alkylation by iodoacetamide is inhibited by NAD+. In the absence of NAD+, hydrolysis of the acylated enzyme is faster than phosphorolysis while the reverse is true in the presence of NAD+. NAD+ accelerates hydrolysis of the 3-phosphoglyceroylated enzyme about 60-fold but decreases the rate of hydrolysis of the furylacryloylated enzyme by a factor of 17. Other examples of the specificity of the induced conformational changes and the probes are described. The conformational changes induced by NAD+ make the protein specifically reactive toward its physiological substrates and less reactive toward extraneous competing compounds.", "contents": "The specificity of induced conformational changes. The case of yeast glyceraldehyde-3-phosphate dehydrogenase. The specificity of induced conformational changes and of the probes used to detect them has been investigated in yeast glyceraldehyde-3-phosphate dehydrogenase. Cyanylation of the active-site SH groups in two of the four identical subunits of glyceraldehyde-3-phosphate dehydrogenase has no effect on reactivity of the unmodified SH groups toward the cyanylating reagent (2-nitro-5-thiocyanogenzoic acid, NTCB) but results in total loss of catalytic activity. Cyanylation of the dicarboxamidomethylated enzyme was four orders of magnitude slower than with the unmodified enzyme in contrast to cyanylation of the dicyanylated enzyme. Cyanylation by NTCB as well as alkylation by iodoacetate and acylation with beta-(2-furyl)acryloyl phosphate are enhanced in the presence of NAD+ while alkylation by iodoacetamide is inhibited by NAD+. In the absence of NAD+, hydrolysis of the acylated enzyme is faster than phosphorolysis while the reverse is true in the presence of NAD+. NAD+ accelerates hydrolysis of the 3-phosphoglyceroylated enzyme about 60-fold but decreases the rate of hydrolysis of the furylacryloylated enzyme by a factor of 17. Other examples of the specificity of the induced conformational changes and the probes are described. The conformational changes induced by NAD+ make the protein specifically reactive toward its physiological substrates and less reactive toward extraneous competing compounds."} {"id": "PMID:169883", "title": "Thermotropic lipid clustering in tetrahymena membranes.", "content": "The effect of temperature on the core structure of endoplasmic reticulum membranes has been visualized directly in cells of the poikilothermic eukaryote Tetrahymena pyriformis by freeze-etch electron microscopy. Moreover, the effect of temperature on the smooth microsomal membrane vesicles isolated from these cells, as well as on the extracted membrane lipids, has been examined by fluorescence probing, electron spin resonance, proton nuclear magnetic resonance, and calorimetry. Freeze-etch electron microscopy of T. pyriformis cells, equilibrated at different temperatures between 28 and 5 degrees, reveals the emergence of smooth areas on the fracture faces of endoplasmic reticulum membranes at temperatures below similar to 17 degrees. In this temperature range, we also find discontinuities in the glucose 6-phosphatase activity, in the fluorescence intensity of 8-anilino-1-naphthalensulfonate, in the partition of 4-doxyldecane, and in the separation of the outer hyperfine extrema of 5-doxylstearic acid in the microsomal membranes. These membranes apparently contain at least two lipid environments of different fluidity as indicated by the 12-doxylstearic acid spin-label. Proton nuclear magnetic resonance of the extracted membrane lipids indicates an abrupt change of the fatty acid chain mobilities at temperatures below similar to 17 degrees. This, however, is not due to a true thermal liquid crystalline in equilibrium crystalline phase transition. Calorimetric measurements also support this conclusion. The thermotropic alterations observed within the membranes are interpreted to be due primarily to a clustering of \"rigid\" liquid crystalline lipid environments which exclude membrane-intercalating proteins.", "contents": "Thermotropic lipid clustering in tetrahymena membranes. The effect of temperature on the core structure of endoplasmic reticulum membranes has been visualized directly in cells of the poikilothermic eukaryote Tetrahymena pyriformis by freeze-etch electron microscopy. Moreover, the effect of temperature on the smooth microsomal membrane vesicles isolated from these cells, as well as on the extracted membrane lipids, has been examined by fluorescence probing, electron spin resonance, proton nuclear magnetic resonance, and calorimetry. Freeze-etch electron microscopy of T. pyriformis cells, equilibrated at different temperatures between 28 and 5 degrees, reveals the emergence of smooth areas on the fracture faces of endoplasmic reticulum membranes at temperatures below similar to 17 degrees. In this temperature range, we also find discontinuities in the glucose 6-phosphatase activity, in the fluorescence intensity of 8-anilino-1-naphthalensulfonate, in the partition of 4-doxyldecane, and in the separation of the outer hyperfine extrema of 5-doxylstearic acid in the microsomal membranes. These membranes apparently contain at least two lipid environments of different fluidity as indicated by the 12-doxylstearic acid spin-label. Proton nuclear magnetic resonance of the extracted membrane lipids indicates an abrupt change of the fatty acid chain mobilities at temperatures below similar to 17 degrees. This, however, is not due to a true thermal liquid crystalline in equilibrium crystalline phase transition. Calorimetric measurements also support this conclusion. The thermotropic alterations observed within the membranes are interpreted to be due primarily to a clustering of \"rigid\" liquid crystalline lipid environments which exclude membrane-intercalating proteins."} {"id": "PMID:169884", "title": "A spin-label study on fusion of red blood cells induced by hemagglutinating virus of Japan.", "content": "Fusion of red blood cells (RBC) induced by hemagglutinating virus of Japan (HVJ) has been studied using a phosphatidylcholine spin label. The spin label was readily incorporated and diffused into the lipid bilayer portion of the viral envelope. The exchange broadening in the electron spin resonance (ESR) spectrum of densely labeled virus disappeared rapidly when the virus was mixed with RBC at 37 degrees. The spectrum gradually approached that of the host cell spin labeled with the phosphatidylcholine label. The results directly indicate transfer and intermixing of phospholipid molecules between the viral envelope and RBC membrane. The transfer reaction was strongly dependent on temperature. No transfer was observed at lower temperatures where the virus adsorbed to the cell and caused aggregation but no hemolysis and fusion. The transfer rate remained negligibly small until 19 degrees and increased rapidly between 25 and 30 degrees. The virus-induced hemolysis showed similar temperature dependence. The transfer rate was greatly reduced under inhibitory conditions of fusion: glutaraldehyde treatment of RBC, trypsin treatment of HVJ, or the presence of concanavalin A. Only slight transfer was observed from fusion-inactive influenza virus to RBC. The transfer was greatly enhanced by the help of HVJ. The close parallelism suggests that the transfer and intermixing are necessary steps to the cell fusion. The transfer rate was dependent on fluidity of the host cell membrane and independent of the viral dose. The virus-induced transfer of phospholipid molecules between RBC's was also detected by the spin label. Its temperature dependence was quite similar to that for the virus-to-cell transfer. The intercellular transfer was nearly proportional to the viral dose.", "contents": "A spin-label study on fusion of red blood cells induced by hemagglutinating virus of Japan. Fusion of red blood cells (RBC) induced by hemagglutinating virus of Japan (HVJ) has been studied using a phosphatidylcholine spin label. The spin label was readily incorporated and diffused into the lipid bilayer portion of the viral envelope. The exchange broadening in the electron spin resonance (ESR) spectrum of densely labeled virus disappeared rapidly when the virus was mixed with RBC at 37 degrees. The spectrum gradually approached that of the host cell spin labeled with the phosphatidylcholine label. The results directly indicate transfer and intermixing of phospholipid molecules between the viral envelope and RBC membrane. The transfer reaction was strongly dependent on temperature. No transfer was observed at lower temperatures where the virus adsorbed to the cell and caused aggregation but no hemolysis and fusion. The transfer rate remained negligibly small until 19 degrees and increased rapidly between 25 and 30 degrees. The virus-induced hemolysis showed similar temperature dependence. The transfer rate was greatly reduced under inhibitory conditions of fusion: glutaraldehyde treatment of RBC, trypsin treatment of HVJ, or the presence of concanavalin A. Only slight transfer was observed from fusion-inactive influenza virus to RBC. The transfer was greatly enhanced by the help of HVJ. The close parallelism suggests that the transfer and intermixing are necessary steps to the cell fusion. The transfer rate was dependent on fluidity of the host cell membrane and independent of the viral dose. The virus-induced transfer of phospholipid molecules between RBC's was also detected by the spin label. Its temperature dependence was quite similar to that for the virus-to-cell transfer. The intercellular transfer was nearly proportional to the viral dose."} {"id": "PMID:169885", "title": "High molecular weight forms of adrenocorticotropic hormone in the mouse pituitary and in a mouse pituitary tumor cell line.", "content": "Denaturing solvents have been used to determine the molecular weight of the adrenocorticotropic hormone (ACTH) activity in mouse pituitary, in an ACTH secreting mouse pituitary tumor cell line (AtT-20/D-16v), and in the tissue culture medium from the pituitary tumor cells. ACTH activity was quantitated by radioimmunoassay and by bioassay. It is possible to utilize guanidine hydrochloride or sodium dodecyl sulfate in characterizing the multiple forms of ACTH because treatment of porcine ACTH (the 39 amino acid polypeptide form of ACTH, alpha(1-39)), pituitary extracts, tumor cell extracts, and tumor cell tissue culture medium with these denaturants does not diminish the immunological ACTH activity. Based on gel filtration in the presence of guanidine hydrocholoride, extracts of the pituitary tumor cells and the mouse pituitary contain three distinct molecular weight classes of ACTH activity. The major form of ACTH has a molecular weight similar to alpha(1-39) (molecular weight 4000-5500), but there are significant amounts of two higher molecular weight forms of ACTH: molecular weight 6500-9000 and molecular weight 20,000-30,000. The 6500-9000 molecular weight form of ACTH is the major form of ACTH in the tissue culture medium; there is no peak of alpha(1-39) size ACTH in the medium. In the radioimmunoasay all three forms of ACTH generate competitive binding curves parallel to that of porcine alpha(1-39); in the bioassay (stimulation of steroidogenesis in a mouse adrenal tumor cell line) the dose response curve for each of the molecular forms of ACTH is parallel to that for porcine alpha(1-39).", "contents": "High molecular weight forms of adrenocorticotropic hormone in the mouse pituitary and in a mouse pituitary tumor cell line. Denaturing solvents have been used to determine the molecular weight of the adrenocorticotropic hormone (ACTH) activity in mouse pituitary, in an ACTH secreting mouse pituitary tumor cell line (AtT-20/D-16v), and in the tissue culture medium from the pituitary tumor cells. ACTH activity was quantitated by radioimmunoassay and by bioassay. It is possible to utilize guanidine hydrochloride or sodium dodecyl sulfate in characterizing the multiple forms of ACTH because treatment of porcine ACTH (the 39 amino acid polypeptide form of ACTH, alpha(1-39)), pituitary extracts, tumor cell extracts, and tumor cell tissue culture medium with these denaturants does not diminish the immunological ACTH activity. Based on gel filtration in the presence of guanidine hydrocholoride, extracts of the pituitary tumor cells and the mouse pituitary contain three distinct molecular weight classes of ACTH activity. The major form of ACTH has a molecular weight similar to alpha(1-39) (molecular weight 4000-5500), but there are significant amounts of two higher molecular weight forms of ACTH: molecular weight 6500-9000 and molecular weight 20,000-30,000. The 6500-9000 molecular weight form of ACTH is the major form of ACTH in the tissue culture medium; there is no peak of alpha(1-39) size ACTH in the medium. In the radioimmunoasay all three forms of ACTH generate competitive binding curves parallel to that of porcine alpha(1-39); in the bioassay (stimulation of steroidogenesis in a mouse adrenal tumor cell line) the dose response curve for each of the molecular forms of ACTH is parallel to that for porcine alpha(1-39)."} {"id": "PMID:169886", "title": "Thyrotropin-releasing hormone regulates the number of its own receptors in the GH3 strain of pituitary cells in culture.", "content": "Thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide, binds rapidly and reversibly to specific membrane receptors on GH3 cells, a clonal strain of rat pituitary cells grown in culture. GH3 cells were incubated for 1-72 hr with unlabeled TRH, washed, and then incubated for 1 hr with [3H]TRH. Under these conditions 80% of any bound, unlabeled TRH exchanges with [3H]TRH in the medium, and the amount of radioactivity bound to the cells gives a measure of the number of TRH receptors. In GH3 cells, the number of available TRH receptors decreased from 92% of control after 1 hr to 35% after 48 or 72 hr of incubation with unlabeled TRH. Binding of [3H]TRH to both intact control and TRH-treated cells was half-maximal at 8 nM [3H]TRH, but the maximum amount of [3H]TRH bound was decreased by 75% in cells previously incubated for 48 hr with unlabeled TRH. Equilibrium binding studies were performed using membrane fractions prepared from control cells and cells previously exposed to TRH for various periods. The dissociation constant of the TRH-receptor complex was the same in all cases, but the maximum amount of TRH bound decreased progressively in membrane fractions from cells incubated with TRH for 1-51 hr. TRH receptors were not found in cytoplasmic fractions of control or TRH-treated cells. The loss of TRH receptors was reversible within 4 days. In the continued presence of the tripeptide the number of receptors remained low for 12 days. After incubation for 2 days with different concentrations of TRH, the number of receptors was decreased to 33% of control at 100-300 nM TRH, and half of this decrease occurred at about 1 nM TRH; half-maximal biological responses occur at 2 nM TRH. The biologically active Ntau-methylhistidyl derivative of TRH also effected a loss of receptors, while three inactive analogs of TRH did not cause reductions in the number of TRH receptors. In cultures incubated for 40 hr with cycloheximide, protein synthesis was inhibited by 85%, but the number of TRH receptors was 76% of control suggesting that the receptor has a long half-life. When GH3 cells were incubated with cycloheximide plus TRH, the number of TRH receptors decreased by only 23% as compared to a decrease of 73% in cells incubated with TRH alone, suggesting that receptor loss is partially dependent on active protein synthesis. We conclude that in GH3 cells TRH regulates the number of its own receptors.", "contents": "Thyrotropin-releasing hormone regulates the number of its own receptors in the GH3 strain of pituitary cells in culture. Thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide, binds rapidly and reversibly to specific membrane receptors on GH3 cells, a clonal strain of rat pituitary cells grown in culture. GH3 cells were incubated for 1-72 hr with unlabeled TRH, washed, and then incubated for 1 hr with [3H]TRH. Under these conditions 80% of any bound, unlabeled TRH exchanges with [3H]TRH in the medium, and the amount of radioactivity bound to the cells gives a measure of the number of TRH receptors. In GH3 cells, the number of available TRH receptors decreased from 92% of control after 1 hr to 35% after 48 or 72 hr of incubation with unlabeled TRH. Binding of [3H]TRH to both intact control and TRH-treated cells was half-maximal at 8 nM [3H]TRH, but the maximum amount of [3H]TRH bound was decreased by 75% in cells previously incubated for 48 hr with unlabeled TRH. Equilibrium binding studies were performed using membrane fractions prepared from control cells and cells previously exposed to TRH for various periods. The dissociation constant of the TRH-receptor complex was the same in all cases, but the maximum amount of TRH bound decreased progressively in membrane fractions from cells incubated with TRH for 1-51 hr. TRH receptors were not found in cytoplasmic fractions of control or TRH-treated cells. The loss of TRH receptors was reversible within 4 days. In the continued presence of the tripeptide the number of receptors remained low for 12 days. After incubation for 2 days with different concentrations of TRH, the number of receptors was decreased to 33% of control at 100-300 nM TRH, and half of this decrease occurred at about 1 nM TRH; half-maximal biological responses occur at 2 nM TRH. The biologically active Ntau-methylhistidyl derivative of TRH also effected a loss of receptors, while three inactive analogs of TRH did not cause reductions in the number of TRH receptors. In cultures incubated for 40 hr with cycloheximide, protein synthesis was inhibited by 85%, but the number of TRH receptors was 76% of control suggesting that the receptor has a long half-life. When GH3 cells were incubated with cycloheximide plus TRH, the number of TRH receptors decreased by only 23% as compared to a decrease of 73% in cells incubated with TRH alone, suggesting that receptor loss is partially dependent on active protein synthesis. We conclude that in GH3 cells TRH regulates the number of its own receptors."} {"id": "PMID:169887", "title": "Photoaffinity labeling of adenosine 3',5'-cyclic monophosphate binding sites of human red cell membranes.", "content": "To identify and investigate the cAMP binding sites of human red cell membranes a photoaffinity analog of cAMP, 8-azidoadenosine 3',5'-cyclic monophosphate (8-N3cAMP), has been synthesized. This analog activates cAMP-dependent protein kinase(s) in the red cell membrane. It exhibits tight, but reversible binding to the membranes which is competitive with cAMP. Photolysis of [32P]-8-N3cAMP with red cell membranes results in covalent incorporation of radioactive label onto two specific membrane proteins. This incorporation requires activating light and is reduced to background levels with addition of low levels of cAMP. Prephotolysis of 8-N3cAMP completely abolished its ability to photolabel membrane proteins. Both the reversible and photocatalyzed binding of 8-N3cAMP show saturation kinetics. The molecular weights of the two primarily labeled proteins are approximately 49,000 and 55,000. The differential effects of cAMP, ATP, and adenosine on the photocatalyzed incorporation of [32P]-8-N3cAMP onto these two proteins suggest that they have biochemically different properties. The potential usefulness of this compound for investigating various molecular aspects of cAMP action is discussed.", "contents": "Photoaffinity labeling of adenosine 3',5'-cyclic monophosphate binding sites of human red cell membranes. To identify and investigate the cAMP binding sites of human red cell membranes a photoaffinity analog of cAMP, 8-azidoadenosine 3',5'-cyclic monophosphate (8-N3cAMP), has been synthesized. This analog activates cAMP-dependent protein kinase(s) in the red cell membrane. It exhibits tight, but reversible binding to the membranes which is competitive with cAMP. Photolysis of [32P]-8-N3cAMP with red cell membranes results in covalent incorporation of radioactive label onto two specific membrane proteins. This incorporation requires activating light and is reduced to background levels with addition of low levels of cAMP. Prephotolysis of 8-N3cAMP completely abolished its ability to photolabel membrane proteins. Both the reversible and photocatalyzed binding of 8-N3cAMP show saturation kinetics. The molecular weights of the two primarily labeled proteins are approximately 49,000 and 55,000. The differential effects of cAMP, ATP, and adenosine on the photocatalyzed incorporation of [32P]-8-N3cAMP onto these two proteins suggest that they have biochemically different properties. The potential usefulness of this compound for investigating various molecular aspects of cAMP action is discussed."} {"id": "PMID:169888", "title": "Photoaffinity labeling of a protein kinase from bovine brain with 8-azidoadenosine 3',5'-monophosphate.", "content": "8-Azidoadenosine 3',5'-monophosphate (8-N3-cAMP) containing 32P has been used as a photoaffinity label specific for the adenosine 3',5'-monophosphate (cAMP) binding site(s) present in a partially purified preparation of soluble protein kinase from bovine brain. 8-N3-cAMP and cAMP were found to compete for the same binding site(s) in this preparation, as determined by a standard filter assay. When this protein preparation was equilibrated with [32P]-8-N3-cAMP, and then irradiated at 253.7 nm, the incorporation of radioactivity was predominantly into a protein with an apparent molecular weight of 49,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. This labeled protein comigrated in the gel with the only protein which is endogenously phosphorylated by [gamma-32P]ATP, a protein which has been shown to be the regulatory subunit of the protein kinase (H. Maeno, P. L. Reyes, T. Ueda, S. A. Rudolph, and P. Greengard (1974), Arch. Biochem. Biophys. 164, 551). The incorporation of [32P]-8-N3-cAMP into this protein was half-maximal at a concentration of 7 x 10(-8) M. In accordance with a proposed mechanism involving the formation of a highly reactive nitrene intermediate upon irradiation of the azide, the incorporation of radioactivity into protein was maximal within 10 min of irradiation, and was almost eliminated by preirradiation of the photolabile ligand. Moreover, this incorporation was virtually abolished by a 50-fold excess of cAMP, but not by AMP, ADP, ATP, or adenosine. We suggest that 8-N3-cAMP may prove to be a useful molecular probe of the cAMP-binding site in receptor proteins and report its use in conjunction with sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a highly sensitive and selective radiochemical marker for cAMP-binding proteins.", "contents": "Photoaffinity labeling of a protein kinase from bovine brain with 8-azidoadenosine 3',5'-monophosphate. 8-Azidoadenosine 3',5'-monophosphate (8-N3-cAMP) containing 32P has been used as a photoaffinity label specific for the adenosine 3',5'-monophosphate (cAMP) binding site(s) present in a partially purified preparation of soluble protein kinase from bovine brain. 8-N3-cAMP and cAMP were found to compete for the same binding site(s) in this preparation, as determined by a standard filter assay. When this protein preparation was equilibrated with [32P]-8-N3-cAMP, and then irradiated at 253.7 nm, the incorporation of radioactivity was predominantly into a protein with an apparent molecular weight of 49,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. This labeled protein comigrated in the gel with the only protein which is endogenously phosphorylated by [gamma-32P]ATP, a protein which has been shown to be the regulatory subunit of the protein kinase (H. Maeno, P. L. Reyes, T. Ueda, S. A. Rudolph, and P. Greengard (1974), Arch. Biochem. Biophys. 164, 551). The incorporation of [32P]-8-N3-cAMP into this protein was half-maximal at a concentration of 7 x 10(-8) M. In accordance with a proposed mechanism involving the formation of a highly reactive nitrene intermediate upon irradiation of the azide, the incorporation of radioactivity into protein was maximal within 10 min of irradiation, and was almost eliminated by preirradiation of the photolabile ligand. Moreover, this incorporation was virtually abolished by a 50-fold excess of cAMP, but not by AMP, ADP, ATP, or adenosine. We suggest that 8-N3-cAMP may prove to be a useful molecular probe of the cAMP-binding site in receptor proteins and report its use in conjunction with sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a highly sensitive and selective radiochemical marker for cAMP-binding proteins."} {"id": "PMID:169889", "title": "DNA binding by cyclic adenosine 3',5'-monophosphate dependent protein kinase from calf thymus nuclei.", "content": "Cyclic adenosine 3',5'-monophosphate (cAMP) dependent protein kinase and proteins specifically binding cAMP have been extracted from calf thymus nuclei and analyzed for their abilities to bind to DNA. Approximately 70% of the cAMP-binding activity in the nucleus can be ascribed to a nuclear acidic protein with physical and biochemical characteristics of the regulatory (R) subunit of cAMP-dependent protein kinase. Several peaks of protein kinase activity and of cAMP-binding activity are resolved by affinity chromatography of nuclear acidic proteins on calf thymus DNA covalently linked to aminoethyl Sephrarose 4B. When an extensively purified protein kinase is subjected to chromatography on the DNA column in the presence of 10(-7) M cAMP, the R subunit of the kinase is eluted from the column at 0.05 M NaCl while the catalytic (C) subunit of the enzyme is eluted at 0.1-0.2 M NaCl. When chromatographed in the presence of histones, the R subunit is retained on the column and is eluted at 0.6-0.9 M NaCl. In the presence of cAMP, association of the C subunit with DNA is enhanced, as determined by sucrose density gradient centrifugation of DNA-protein kinase complexes. cAMP increases the capacity of the calf thymus cAMP-dependent protein kinase preparation to bind labeled calf thymus DNA, as determined by a technique employing filter retention of DNA-protein complexes. This protein kinase preparation binds calf thymus DNA in preference to salmon DNA, Escherichia coli DNA, or yeast RNA. Binding of protein kinases to DNA may be part of a mechanism for localizing cyclic nucleotide stimulated protein phosphorylation at specific sites in the chromatin.", "contents": "DNA binding by cyclic adenosine 3',5'-monophosphate dependent protein kinase from calf thymus nuclei. Cyclic adenosine 3',5'-monophosphate (cAMP) dependent protein kinase and proteins specifically binding cAMP have been extracted from calf thymus nuclei and analyzed for their abilities to bind to DNA. Approximately 70% of the cAMP-binding activity in the nucleus can be ascribed to a nuclear acidic protein with physical and biochemical characteristics of the regulatory (R) subunit of cAMP-dependent protein kinase. Several peaks of protein kinase activity and of cAMP-binding activity are resolved by affinity chromatography of nuclear acidic proteins on calf thymus DNA covalently linked to aminoethyl Sephrarose 4B. When an extensively purified protein kinase is subjected to chromatography on the DNA column in the presence of 10(-7) M cAMP, the R subunit of the kinase is eluted from the column at 0.05 M NaCl while the catalytic (C) subunit of the enzyme is eluted at 0.1-0.2 M NaCl. When chromatographed in the presence of histones, the R subunit is retained on the column and is eluted at 0.6-0.9 M NaCl. In the presence of cAMP, association of the C subunit with DNA is enhanced, as determined by sucrose density gradient centrifugation of DNA-protein kinase complexes. cAMP increases the capacity of the calf thymus cAMP-dependent protein kinase preparation to bind labeled calf thymus DNA, as determined by a technique employing filter retention of DNA-protein complexes. This protein kinase preparation binds calf thymus DNA in preference to salmon DNA, Escherichia coli DNA, or yeast RNA. Binding of protein kinases to DNA may be part of a mechanism for localizing cyclic nucleotide stimulated protein phosphorylation at specific sites in the chromatin."} {"id": "PMID:169890", "title": "Optical and magnetic resonance studies of formate binding to horse liver catalase and sperm whale myoglobin.", "content": "The binding of formate ion, a substrate for the peroxidatic reaction of catalase, has been investigated by magnetic resonance techniques. Comparative studies of formate binding to ferric myoglobin have also been performed. The nuclear magnetic relaxation (NMR) rate of formate and water protons is enhanced by the presence of ferric horse liver catalase. The enhancement is not changed significantly by the addition of cyanide, indicating that water and formate are still bound in the presence of cyanide. Formate proton to heme iron distances determined by magnetic resonance techniques indicate that formate does not directly bind to the heme iron of catalase or myoglobin but to the globin, and NMR relaxation occurs as a result of outersphere mechanisms. Evidence that water forms an innersphere complex with the iron atom of the catalase heme is presented. In similar experiments with ferric myoglobin, the addition of cyanide caused a large decrease in the enhancement of the proton relaxation rate of both formate and water, indicating the displacement of water and formate from the heme and the vicinity of the heme, respectively. Broad, high-spin, ferric ion electron paramagnetic resonance absorptions of catalase and myoglobin at room temperature obtained in the presence and absence of formate show that formate does not alter appreciably the heme environment of catalase or myoglobin or the spin state of the heme iron. Studies on the binding of formate to catalase as monitored by changes in the heme absorption spectrum in the visible region show one-to-one stoichiometry with heme concentration. However, the small changes observed in the visible region of the optical spectrum on addition of formate ion are attributed to a secondary effect of formate on the heme environment, rather than direct binding of formate to the heme moiety.", "contents": "Optical and magnetic resonance studies of formate binding to horse liver catalase and sperm whale myoglobin. The binding of formate ion, a substrate for the peroxidatic reaction of catalase, has been investigated by magnetic resonance techniques. Comparative studies of formate binding to ferric myoglobin have also been performed. The nuclear magnetic relaxation (NMR) rate of formate and water protons is enhanced by the presence of ferric horse liver catalase. The enhancement is not changed significantly by the addition of cyanide, indicating that water and formate are still bound in the presence of cyanide. Formate proton to heme iron distances determined by magnetic resonance techniques indicate that formate does not directly bind to the heme iron of catalase or myoglobin but to the globin, and NMR relaxation occurs as a result of outersphere mechanisms. Evidence that water forms an innersphere complex with the iron atom of the catalase heme is presented. In similar experiments with ferric myoglobin, the addition of cyanide caused a large decrease in the enhancement of the proton relaxation rate of both formate and water, indicating the displacement of water and formate from the heme and the vicinity of the heme, respectively. Broad, high-spin, ferric ion electron paramagnetic resonance absorptions of catalase and myoglobin at room temperature obtained in the presence and absence of formate show that formate does not alter appreciably the heme environment of catalase or myoglobin or the spin state of the heme iron. Studies on the binding of formate to catalase as monitored by changes in the heme absorption spectrum in the visible region show one-to-one stoichiometry with heme concentration. However, the small changes observed in the visible region of the optical spectrum on addition of formate ion are attributed to a secondary effect of formate on the heme environment, rather than direct binding of formate to the heme moiety."} {"id": "PMID:169891", "title": "A heat stable paraoxonase (O,O-diethyl O-p-nitrophenyl phosphate O-p-nitrophenyl hydrolase) from Russell's viper venom.", "content": "Fractionation of Russell's viper venom revealed separate phosphohydrolase activities directed against p-nitrophenyl phosphate, bis(p-nitrophenyl) phosphate, p-nitrophenylthymidylic acid, and O,O-diethyl p-nitrophenyl phosphate (paraoxon). On gel fractionation, the first two activities are eluted ahead of the latter. They could be resolved further by phosphocellulose cation exchange chromatography. The hydrolytic activities directed against p-nitrophenylthymidylic acid hydrolyzing component is heat labile, while the paraoxon hydrolyzing component manifests an unusually high degree of heat stability. Gel filtration yields 9600 for the molecular weight of the \"paraoxonase\". This enzyme, as all known enzymes of this type, requires the presence of a divalent cation. Maximum activity is obtained in the presence of Ca2+. In the presence of Sr2+ the reaction rate is 50% of that of Ca2+; other divalent cations show lower activities. The presence of the enzyme is species specific. Of four species tested, only Russell's viper venom showed significant paraoxonase activity. Enzyme activity is intact following incubation with iodoacetate of p-chloromercuribenzoate. Activity is partially preserved even in the presence of 8 M urea.", "contents": "A heat stable paraoxonase (O,O-diethyl O-p-nitrophenyl phosphate O-p-nitrophenyl hydrolase) from Russell's viper venom. Fractionation of Russell's viper venom revealed separate phosphohydrolase activities directed against p-nitrophenyl phosphate, bis(p-nitrophenyl) phosphate, p-nitrophenylthymidylic acid, and O,O-diethyl p-nitrophenyl phosphate (paraoxon). On gel fractionation, the first two activities are eluted ahead of the latter. They could be resolved further by phosphocellulose cation exchange chromatography. The hydrolytic activities directed against p-nitrophenylthymidylic acid hydrolyzing component is heat labile, while the paraoxon hydrolyzing component manifests an unusually high degree of heat stability. Gel filtration yields 9600 for the molecular weight of the \"paraoxonase\". This enzyme, as all known enzymes of this type, requires the presence of a divalent cation. Maximum activity is obtained in the presence of Ca2+. In the presence of Sr2+ the reaction rate is 50% of that of Ca2+; other divalent cations show lower activities. The presence of the enzyme is species specific. Of four species tested, only Russell's viper venom showed significant paraoxonase activity. Enzyme activity is intact following incubation with iodoacetate of p-chloromercuribenzoate. Activity is partially preserved even in the presence of 8 M urea."} {"id": "PMID:169892", "title": "Functional consequences of modifying highly reactive arginyl residues of fructose 1,6-bisphosphatase. Loss of monovalent cation activation.", "content": "Modification of pig kidney fructose 1,6-bisphosphatase with 2,3-butanedione (in the presence of AMP) results in the loss of activation of the enzyme by monovalent cations. Under these conditions about 8 arginyl residues per mole of enzyme were modified. No other residues were modified. No loss of monovalent cation activation occurs when modification with 2,3-butanedione is carried out in the presence of AMP plus the substrate fructose 1,6-bisphosphate and 3.2 less arginyl residues were modified. Since fructose 1,6-bisphosphatase contains 4 subunits, it is suggested that one arginyl residue per subunit plays an essential role in monovalent cation activation of the enzyme. Studies on sulfhydryl group reactivity toward 5,5'-dithiobis(2-nitrobenzoic acid) explain the protection exerted by fructose 1,6-bisphosphate against the loss of monovalent cation activation in terms of an enzyme conformational change induced by substrate, which makes unreactive the essential arginyl residue. The results of the present paper, as well as previous evidence, are discussed in terms of the mechanism of monovalent cation activation of fructose 1,6-biphosphatase.", "contents": "Functional consequences of modifying highly reactive arginyl residues of fructose 1,6-bisphosphatase. Loss of monovalent cation activation. Modification of pig kidney fructose 1,6-bisphosphatase with 2,3-butanedione (in the presence of AMP) results in the loss of activation of the enzyme by monovalent cations. Under these conditions about 8 arginyl residues per mole of enzyme were modified. No other residues were modified. No loss of monovalent cation activation occurs when modification with 2,3-butanedione is carried out in the presence of AMP plus the substrate fructose 1,6-bisphosphate and 3.2 less arginyl residues were modified. Since fructose 1,6-bisphosphatase contains 4 subunits, it is suggested that one arginyl residue per subunit plays an essential role in monovalent cation activation of the enzyme. Studies on sulfhydryl group reactivity toward 5,5'-dithiobis(2-nitrobenzoic acid) explain the protection exerted by fructose 1,6-bisphosphate against the loss of monovalent cation activation in terms of an enzyme conformational change induced by substrate, which makes unreactive the essential arginyl residue. The results of the present paper, as well as previous evidence, are discussed in terms of the mechanism of monovalent cation activation of fructose 1,6-biphosphatase."} {"id": "PMID:169893", "title": "Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5' terminus.", "content": "KOH digestion of methyl-labeled poly(A)+ mRNA purified by (dT)-cellulose chromatography produced mononucleotide and multiple peaks of a large oligonucleotide (-6 to -8 charge) when separated on the basis of charge by Pellionex-WAX high-speed liquid chromatography in 7 M urea. Heat denaturation of the RNA before application to (dT)-cellulose was required to release contaminants (mostly 18S rRNA) that persisted even after repeated binding to (dT)-cellulose at room temperature. Analysis of the purified poly(A)+ mRNA by enzyme digestion, acid hydrolysis, and a variety of chromatographic techniques has shown that the monucleotide (53%) is due entirely to N6-methyladenosine. The large oligonucleotides (47%) were found to contain 7-methylguanosine and the 2'-0-methyl derivatives of all four nucleosides. No radioactivity was found associated with the poly(A) segment. Periodate oxidation of the mRNA followed by beta elimination released only labeled 7-methylguanine consistent with a blocked 5' terminus containing an unusual 5'-5' bond. Alkaline phosphatase treatment of intact mRNA had no effect on the migration of the KOH produced oligonucleotides on Pellionex-WAX. When RNA from which 7-methylguanine was removed by beta elimination was used for the phosphatase treatment, distinct dinucleotides (NmpNp) and trinucleotides (NmpNmpNp) occurred after KOH hydrolysis and Pellionex-WAX chromatography. Thus Novikoff hepatoma poly(A)+ mRNA molecules can contain either one or two 2'-0-methylnucleotides linked by a 5'-5' bond to a terminal 7-methylguanosine and the 2'-0-methylation can occur with any of the four nucleotides. The 5' terminus may be represented by m7G5'ppp5' (Nmp)lor2Np, a general structure proposed earlier as a possible 5' terminus for all eucaryotic mRNA molecules (Rottman, F., Shatkin, A., and Perry, R. (1974), Cell 3, 197). The composition analyses indicate that there are 3.0 N6-methyladenosine residues, 1.0 7-methylguanosine residue, and 1.7 2'-0-methylnucleoside residues per average mRNA molecule.", "contents": "Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5' terminus. KOH digestion of methyl-labeled poly(A)+ mRNA purified by (dT)-cellulose chromatography produced mononucleotide and multiple peaks of a large oligonucleotide (-6 to -8 charge) when separated on the basis of charge by Pellionex-WAX high-speed liquid chromatography in 7 M urea. Heat denaturation of the RNA before application to (dT)-cellulose was required to release contaminants (mostly 18S rRNA) that persisted even after repeated binding to (dT)-cellulose at room temperature. Analysis of the purified poly(A)+ mRNA by enzyme digestion, acid hydrolysis, and a variety of chromatographic techniques has shown that the monucleotide (53%) is due entirely to N6-methyladenosine. The large oligonucleotides (47%) were found to contain 7-methylguanosine and the 2'-0-methyl derivatives of all four nucleosides. No radioactivity was found associated with the poly(A) segment. Periodate oxidation of the mRNA followed by beta elimination released only labeled 7-methylguanine consistent with a blocked 5' terminus containing an unusual 5'-5' bond. Alkaline phosphatase treatment of intact mRNA had no effect on the migration of the KOH produced oligonucleotides on Pellionex-WAX. When RNA from which 7-methylguanine was removed by beta elimination was used for the phosphatase treatment, distinct dinucleotides (NmpNp) and trinucleotides (NmpNmpNp) occurred after KOH hydrolysis and Pellionex-WAX chromatography. Thus Novikoff hepatoma poly(A)+ mRNA molecules can contain either one or two 2'-0-methylnucleotides linked by a 5'-5' bond to a terminal 7-methylguanosine and the 2'-0-methylation can occur with any of the four nucleotides. The 5' terminus may be represented by m7G5'ppp5' (Nmp)lor2Np, a general structure proposed earlier as a possible 5' terminus for all eucaryotic mRNA molecules (Rottman, F., Shatkin, A., and Perry, R. (1974), Cell 3, 197). The composition analyses indicate that there are 3.0 N6-methyladenosine residues, 1.0 7-methylguanosine residue, and 1.7 2'-0-methylnucleoside residues per average mRNA molecule."} {"id": "PMID:169894", "title": "Nuclear ribonucleoprotein complexes containing U1 and U2 RNA.", "content": "Nuclear ribonucleoprotein (RNP) complexes that contain the U1 and U2 RNA of chromatin of Novikoff hepatoma cells were extracted with 0.01 M Tris-HCl (pH 8.0) after the nuclei were initially washed with 0.075 M NaCl and 0.025 M EDTA (pH 8.0). These RNP complexes were purified by chromatography on Sepharose 6B columns and centrifugation on sucrose density gradients. The identity of the U1 and U2 RNA in these particles was established by their electrophoretic mobility in polyacrylamide gels and their T1 RNase fingerprints which were identical with those of authentic U1 and U2 RNA (R. Reddy et al. (1974), J. Biol. Chem.249, 6486-6494; H. Shibata et al. (1974), Mol. Cell. Biochem. 4, 3-19). The nuclear riboncleoproteins had a buoyant density of 1.47 g/ml in CsCl gradients. Two-dimensional polyacrylamide gel electrophoresis of their proteins showed these RNP complexes contain 10 polypeptide spots, of which two are phosphorylated in vivo.", "contents": "Nuclear ribonucleoprotein complexes containing U1 and U2 RNA. Nuclear ribonucleoprotein (RNP) complexes that contain the U1 and U2 RNA of chromatin of Novikoff hepatoma cells were extracted with 0.01 M Tris-HCl (pH 8.0) after the nuclei were initially washed with 0.075 M NaCl and 0.025 M EDTA (pH 8.0). These RNP complexes were purified by chromatography on Sepharose 6B columns and centrifugation on sucrose density gradients. The identity of the U1 and U2 RNA in these particles was established by their electrophoretic mobility in polyacrylamide gels and their T1 RNase fingerprints which were identical with those of authentic U1 and U2 RNA (R. Reddy et al. (1974), J. Biol. Chem.249, 6486-6494; H. Shibata et al. (1974), Mol. Cell. Biochem. 4, 3-19). The nuclear riboncleoproteins had a buoyant density of 1.47 g/ml in CsCl gradients. Two-dimensional polyacrylamide gel electrophoresis of their proteins showed these RNP complexes contain 10 polypeptide spots, of which two are phosphorylated in vivo."} {"id": "PMID:169895", "title": "Steroid-receptor quantitation and characterization by electrophoresis in highly cross-linked polyacrylamide gels.", "content": "Conditions for discontinuous polyacrylamide gel electrophoresis have been defined in which progesterone receptors of chick oviduct cytosol and a variety of steroid-binding proteins from other sources are stable and amenable to quantitative analysis. The essential modifications from standard procedures include the use of (1) separation gels in which the cross-linking agent/acrylamide monomer = 15:85, (2) glycerol (10% v/v) in all phases of the Trisglycine-HCl buffer system (pH 10.2 in the separation phase during electrophoresis at 0 degrees), and (3) a layer of a charged reducing agent, thioglycolate, beneath the sample layer. Electrophoresis of untreated oviduct cytosol labeled with [3H]progesterone +/- competing steroids revealed a heterodisperse slow peak and a sharp fast peak. Both peaks displayed the steroid-binding specificity and saturability that are characteristic of intracellular receptors. Recovery of steroid from both the slow and fast components increased linearly with sample load up to 60 mul of cytosol (1.2 mg of protein)/gel (6 mm diameter). The specific progesterone binding detected by this technique was comparable to that detected by charcoal-dextran treatment or ion exchange filtration. Relative electrophoretic mobilities (Rf) of globular protein standards and steroid-protein complexes in cytosol and chick serum were measured in separation gels with total gel concentrations (T) systematically varied from 5 to 15% (w/v). Data were processed by computer programs to obtain weighted linear regressions of log Rf on T (Ferguson plots) and the joint 95% confidence limits of the slopes (-KR) and intercepts of these plots. Molecular radii (R) of the binding components and apparent molecular weights (M) were calculated from the linear correlation of R with KR 1/2 for the standards. The value of M is approximately 158,000 obtained for the cytosol fast component was independent of the length of the separation gel, the presence of a stacking gel or prior exposure of the cytosol to KCl. It was higher than expected from the sedimentation coefficient of 4.2 S in the same pH 10.2 buffer. Electrophoresis in 170-mm separation gels without stacking gels revealed that KCl extracts of protamine-precipitated cytosol contain a different receptor form, of lower net negative charge than the cytosol fast form. The results demonstrate the utility of electrophoresis in highly cross-linked gels of several concentrations to discriminate between various receptor forms and steroid-binding components of serum. This method may lead to overestimates of M for highly asymmetric receptor forms.", "contents": "Steroid-receptor quantitation and characterization by electrophoresis in highly cross-linked polyacrylamide gels. Conditions for discontinuous polyacrylamide gel electrophoresis have been defined in which progesterone receptors of chick oviduct cytosol and a variety of steroid-binding proteins from other sources are stable and amenable to quantitative analysis. The essential modifications from standard procedures include the use of (1) separation gels in which the cross-linking agent/acrylamide monomer = 15:85, (2) glycerol (10% v/v) in all phases of the Trisglycine-HCl buffer system (pH 10.2 in the separation phase during electrophoresis at 0 degrees), and (3) a layer of a charged reducing agent, thioglycolate, beneath the sample layer. Electrophoresis of untreated oviduct cytosol labeled with [3H]progesterone +/- competing steroids revealed a heterodisperse slow peak and a sharp fast peak. Both peaks displayed the steroid-binding specificity and saturability that are characteristic of intracellular receptors. Recovery of steroid from both the slow and fast components increased linearly with sample load up to 60 mul of cytosol (1.2 mg of protein)/gel (6 mm diameter). The specific progesterone binding detected by this technique was comparable to that detected by charcoal-dextran treatment or ion exchange filtration. Relative electrophoretic mobilities (Rf) of globular protein standards and steroid-protein complexes in cytosol and chick serum were measured in separation gels with total gel concentrations (T) systematically varied from 5 to 15% (w/v). Data were processed by computer programs to obtain weighted linear regressions of log Rf on T (Ferguson plots) and the joint 95% confidence limits of the slopes (-KR) and intercepts of these plots. Molecular radii (R) of the binding components and apparent molecular weights (M) were calculated from the linear correlation of R with KR 1/2 for the standards. The value of M is approximately 158,000 obtained for the cytosol fast component was independent of the length of the separation gel, the presence of a stacking gel or prior exposure of the cytosol to KCl. It was higher than expected from the sedimentation coefficient of 4.2 S in the same pH 10.2 buffer. Electrophoresis in 170-mm separation gels without stacking gels revealed that KCl extracts of protamine-precipitated cytosol contain a different receptor form, of lower net negative charge than the cytosol fast form. The results demonstrate the utility of electrophoresis in highly cross-linked gels of several concentrations to discriminate between various receptor forms and steroid-binding components of serum. This method may lead to overestimates of M for highly asymmetric receptor forms."} {"id": "PMID:169896", "title": "Quantitative demonstration of the reciprocity of ligand effects in the ternary complex of chicken heart lactate dehydrogenase with nicotinamide adenine dinucleotide oxalate.", "content": "The reciprocity of effects of two ligands simultaneously bound to a protein as a ternary complex may be proven by measurements of four standard free energies of binding. Two of these are for the binding of each ligand in the absence of the other, and the other two for the binding of each ligand in the presence of saturating amounts of the other (conditional free energies). These four quantities have been measured for the complexes of oxalate and nicotinamide adenine dinucleotide with chick heart lactate dehydrogenase. The differences between conditional and unconditional free energies are: oxalate, -1.1 +/- 0.3 kcal; NADH,-1.3 +/- 0.2 kcal, thus proving the reciprocity within experimental error.", "contents": "Quantitative demonstration of the reciprocity of ligand effects in the ternary complex of chicken heart lactate dehydrogenase with nicotinamide adenine dinucleotide oxalate. The reciprocity of effects of two ligands simultaneously bound to a protein as a ternary complex may be proven by measurements of four standard free energies of binding. Two of these are for the binding of each ligand in the absence of the other, and the other two for the binding of each ligand in the presence of saturating amounts of the other (conditional free energies). These four quantities have been measured for the complexes of oxalate and nicotinamide adenine dinucleotide with chick heart lactate dehydrogenase. The differences between conditional and unconditional free energies are: oxalate, -1.1 +/- 0.3 kcal; NADH,-1.3 +/- 0.2 kcal, thus proving the reciprocity within experimental error."} {"id": "PMID:169897", "title": "Carbon-13 nuclear magnetic resonance spectroscopy of [2-13C]carboxymethylcytochrome c.", "content": "Horse heart cytochrome c has been carboxymethylated under various reaction conditions using [2-13C]bromoacetate. Direct analysis of reaction products using 13C nuclear magnetic resonance spectroscopy shows that the protein can be much more extensively modified than has previously been assumed. The proximity of one carboxymethylmethionine residue to the paramagnetic center of the ferric protein allows it to be distinguished from a more constant carboxymethylmethionine residue on the basis of the chemical shift of its labeled methylene group. Refolding of cytochrome c after alkylation at low pH apparently gives a different configuration of modified methionine residues within the protein compared to that produced by alkylation at neutral pH in the presence of cyanide.", "contents": "Carbon-13 nuclear magnetic resonance spectroscopy of [2-13C]carboxymethylcytochrome c. Horse heart cytochrome c has been carboxymethylated under various reaction conditions using [2-13C]bromoacetate. Direct analysis of reaction products using 13C nuclear magnetic resonance spectroscopy shows that the protein can be much more extensively modified than has previously been assumed. The proximity of one carboxymethylmethionine residue to the paramagnetic center of the ferric protein allows it to be distinguished from a more constant carboxymethylmethionine residue on the basis of the chemical shift of its labeled methylene group. Refolding of cytochrome c after alkylation at low pH apparently gives a different configuration of modified methionine residues within the protein compared to that produced by alkylation at neutral pH in the presence of cyanide."} {"id": "PMID:169898", "title": "A protective function of superoxide dismutase during respiratory chain activity.", "content": "(1) Aerobic incubation of heart muscle submitochondrial particles in phosphate buffer after treatment with NADH causes a progressive and substantial inhibition of the NADH oxidation system. Succinate oxidation remains almost unaffected by NADH treatment. (2) The loss of NADH oxidase activity is due to an inhibition of the respiratory chain-linked NADH dehydrogenase. This inhibition of the enzyme is very similar to that caused by combination of the organic mercurial mersalyl with NADH dehydrogenase. (3) The inhibition of NADH oxidation is largely prevented by compounds that are known to react with superoxide ions (02-.), including superoxide dismutase, cytochrome c, tiron and Mn2+. EDTA also has a protective effect, but a number of other metal chelating agents, and several proteins, including catalase, are without effect. (4) It is concluded that the inhibition of NADH oxidation of NADH oxidation by superoxide ions or by mersalyl is reversible and is therefore not due to the loss of oxidoreduction components from the respiratory chain or to an irreversible change in protein conformation. (6) The function of mitochondrial superxide dismutase is discussed in relation to the key role of NADH dehydrogenase in energy-conserving reactions and the formation of hydrogen peroxide during mitochondrial oxidations.", "contents": "A protective function of superoxide dismutase during respiratory chain activity. (1) Aerobic incubation of heart muscle submitochondrial particles in phosphate buffer after treatment with NADH causes a progressive and substantial inhibition of the NADH oxidation system. Succinate oxidation remains almost unaffected by NADH treatment. (2) The loss of NADH oxidase activity is due to an inhibition of the respiratory chain-linked NADH dehydrogenase. This inhibition of the enzyme is very similar to that caused by combination of the organic mercurial mersalyl with NADH dehydrogenase. (3) The inhibition of NADH oxidation is largely prevented by compounds that are known to react with superoxide ions (02-.), including superoxide dismutase, cytochrome c, tiron and Mn2+. EDTA also has a protective effect, but a number of other metal chelating agents, and several proteins, including catalase, are without effect. (4) It is concluded that the inhibition of NADH oxidation of NADH oxidation by superoxide ions or by mersalyl is reversible and is therefore not due to the loss of oxidoreduction components from the respiratory chain or to an irreversible change in protein conformation. (6) The function of mitochondrial superxide dismutase is discussed in relation to the key role of NADH dehydrogenase in energy-conserving reactions and the formation of hydrogen peroxide during mitochondrial oxidations."} {"id": "PMID:169899", "title": "Chlorophyll radical cation in photosystem II of chloroplasts. Millisecond decay at low temperature.", "content": "We compare the absorption changes, in the near infrared and in the green part of the spectrum, induced in spinach chloroplasts suspensions, at -- 170 degrees C, by continuous light and by flashes. (1) Following flash excitation, an absorption increase peaking at 825 nm which reverses rapidly (t 1/2 = 3.0 ms) is not affected by ferricyanide; it is suppressed when chloroplasts are preilluminated in the presence of 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea (DCMU) and hydroxylamine. The reversion of that signal is simultaneous with a partial back reoxidation of C-550 (fully reduced by the flash) and with partial (about 25%) oxidation of cytochrome b559. The magnitude of the signal peaking at 825 nm (that we attribute to the radical cation of the trap chlorophyll of Photosystem II, acting as a primary electron donor) decreases progressively within a series of successive flashes. (2) An absorption increase (40% of which is slowly reversible) with a broad peak around 810 nm is induced by continuous light or by a flash. It is suppressed by pretreatment with ferricyanide, but it is little affected by the treatment with 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea and hydroxylamine. We attribute it to oxidized P700. (3) With chloroplasts pretreated with 10 mM ferricyanide, an absorption increase, whose magnitude is nearly independent of wavelength between 790 and 870 nm, can be induced by continuous light. One saturating flash produces only 20% of the signal. This absorption change (20% of which is reversible in 30 s) might be due to a secondary donor of Photosystem II.", "contents": "Chlorophyll radical cation in photosystem II of chloroplasts. Millisecond decay at low temperature. We compare the absorption changes, in the near infrared and in the green part of the spectrum, induced in spinach chloroplasts suspensions, at -- 170 degrees C, by continuous light and by flashes. (1) Following flash excitation, an absorption increase peaking at 825 nm which reverses rapidly (t 1/2 = 3.0 ms) is not affected by ferricyanide; it is suppressed when chloroplasts are preilluminated in the presence of 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea (DCMU) and hydroxylamine. The reversion of that signal is simultaneous with a partial back reoxidation of C-550 (fully reduced by the flash) and with partial (about 25%) oxidation of cytochrome b559. The magnitude of the signal peaking at 825 nm (that we attribute to the radical cation of the trap chlorophyll of Photosystem II, acting as a primary electron donor) decreases progressively within a series of successive flashes. (2) An absorption increase (40% of which is slowly reversible) with a broad peak around 810 nm is induced by continuous light or by a flash. It is suppressed by pretreatment with ferricyanide, but it is little affected by the treatment with 3-(3',4'-dichlorophenyl)-1,1'-dimethylurea and hydroxylamine. We attribute it to oxidized P700. (3) With chloroplasts pretreated with 10 mM ferricyanide, an absorption increase, whose magnitude is nearly independent of wavelength between 790 and 870 nm, can be induced by continuous light. One saturating flash produces only 20% of the signal. This absorption change (20% of which is reversible in 30 s) might be due to a secondary donor of Photosystem II."} {"id": "PMID:169900", "title": "Surface binding and interiorization of homologous and heterologous serum lipoproteins by rat aortic smooth muscle cells in culture.", "content": "Rat aortic smooth muscle cells in culture were incubated with rat or human iodinated low and high density lipoprotein at 5-50 mug/ml for 3 h. With the homologous lipoproteins, 25-49% of total cellular protein radioactivity was trypsin releasable and was considered as surface-bound radioactivity, while the balance represented cellular uptake. The ratio of surface-bound to cellular label was higher when the cells were incubated with human lipoproteins and was about 9 : 1 with human high density lipoprotein. Cellular uptake of rat low density lipoprotein was about twice that of rat high density lipoprotein, while degradation of labeled protein, which had presumably followed protein uptake, was similar and ranged from 20 to 25% of protein uptake in 3 h. Experiments designed to test the effect of cell density on lipoprotein uptake have shown that the uptake was related inversely to cell density. Thus, the lower lipoprotein uptake encountered in the rat smooth muscle cells, compared to that described for human fibroblasts (Goldstein, J.L. and Brown, M.S. (1974) J. Biol. Chem. 249, 5153-5162), could be due in part to the much lower cell density used in the latter studies, as well as to cell type and species difference.", "contents": "Surface binding and interiorization of homologous and heterologous serum lipoproteins by rat aortic smooth muscle cells in culture. Rat aortic smooth muscle cells in culture were incubated with rat or human iodinated low and high density lipoprotein at 5-50 mug/ml for 3 h. With the homologous lipoproteins, 25-49% of total cellular protein radioactivity was trypsin releasable and was considered as surface-bound radioactivity, while the balance represented cellular uptake. The ratio of surface-bound to cellular label was higher when the cells were incubated with human lipoproteins and was about 9 : 1 with human high density lipoprotein. Cellular uptake of rat low density lipoprotein was about twice that of rat high density lipoprotein, while degradation of labeled protein, which had presumably followed protein uptake, was similar and ranged from 20 to 25% of protein uptake in 3 h. Experiments designed to test the effect of cell density on lipoprotein uptake have shown that the uptake was related inversely to cell density. Thus, the lower lipoprotein uptake encountered in the rat smooth muscle cells, compared to that described for human fibroblasts (Goldstein, J.L. and Brown, M.S. (1974) J. Biol. Chem. 249, 5153-5162), could be due in part to the much lower cell density used in the latter studies, as well as to cell type and species difference."} {"id": "PMID:169901", "title": "Effect of ascorbic acid on ACTH-induced cyclic AMP formation and steroidogenesis in isolated adrenal cells of vitamin E-deficient rats.", "content": "Isolated adrenal cells from Vitamin E-deficient and control rats were prepared by a trypsin digestion method. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) formation was studied in response to adrenocorticotropin (ACTH) in the presence and absence of ascorbate by measuring the conversion of prelabeled adenosine 5'-triphosphate [14C]ATP to cyclic [14C]AMP. Ascorbate (0.5 mM) inhibited ACTH-induced cyclic [14C]AMP formation in adrenal cells isolated from Vitamin E-deficient rats but had no effect in the control cells. The inhibitory effect of ascorbate on ACTH-induced cyclic AMP formation in Vitamin E-deficient rats decreased as the concentration of ACTH increased. In Vitamin E-deficient rats ascorbate inhibited ACTH-induced cyclic [14C]AMP formation after 30 min of incubation. There was no further significant accumulation of cyclic [14C]AMP at 60 min or 120 min although in the absence of ascorbate cyclic [14C]AMP continued to be formed. The in vitro addition of alpha-tocopherol reduced the inhibition of ACTH-induced cyclic [14C]AMP formation by ascorbate in Vitamin E-deficient rats. These studies suggest that alpha-tocopherol and ascorbate may affect ACTH-induced cyclic AMP formation through interaction with the membrane-bound enzyme adenylate cyclase.", "contents": "Effect of ascorbic acid on ACTH-induced cyclic AMP formation and steroidogenesis in isolated adrenal cells of vitamin E-deficient rats. Isolated adrenal cells from Vitamin E-deficient and control rats were prepared by a trypsin digestion method. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) formation was studied in response to adrenocorticotropin (ACTH) in the presence and absence of ascorbate by measuring the conversion of prelabeled adenosine 5'-triphosphate [14C]ATP to cyclic [14C]AMP. Ascorbate (0.5 mM) inhibited ACTH-induced cyclic [14C]AMP formation in adrenal cells isolated from Vitamin E-deficient rats but had no effect in the control cells. The inhibitory effect of ascorbate on ACTH-induced cyclic AMP formation in Vitamin E-deficient rats decreased as the concentration of ACTH increased. In Vitamin E-deficient rats ascorbate inhibited ACTH-induced cyclic [14C]AMP formation after 30 min of incubation. There was no further significant accumulation of cyclic [14C]AMP at 60 min or 120 min although in the absence of ascorbate cyclic [14C]AMP continued to be formed. The in vitro addition of alpha-tocopherol reduced the inhibition of ACTH-induced cyclic [14C]AMP formation by ascorbate in Vitamin E-deficient rats. These studies suggest that alpha-tocopherol and ascorbate may affect ACTH-induced cyclic AMP formation through interaction with the membrane-bound enzyme adenylate cyclase."} {"id": "PMID:169902", "title": "Ontogeny of cyclic AMP-dependent protein phosphokinase during hepatic development of the rat.", "content": "The ontogeny of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) and cyclic AMP-binding activity in subcellular fractions of liver was examined during prenatal and postnatal development of the male rat. 1. Protein kinase activity and cyclic AMP-binding activity were found in the nuclear, microsomal, lysosomal-mitochondrial, and soluble liver fractions. 2. The protein kinase activity of the soluble (105 000 X g supernatant) fraction measured with histone F1 as substrate was stimulated by cyclic AMP. Cyclic AMP did not stimulate the protein kinase activity of the particulate fractions. 3. The protein kinase activity of all subcellular fractions increased rapidly from the activity observed in prenatal liver (3-4 days before birth) to reach maximal activity in 2-day-old rats. Thereafter, the protein kinase activity declined more slowly and regained the prenatal levels at 10 days after birth. 4. Considerable latent protein kinase activity was associated with liver microsomal fractions which could be activated by treatment of microsomes with Triton X-100. The latent microsomal protein kinase activity was highest in prenatal liver, at the time of birth, and 2 days after birth. During the subsequent postnatal development the latent microsomal protein kinase activity gradually declined to insignificantly low levels. 5. During the developmental period examined (4 days before birth to age 60-90 days) marked alterations of the cyclic AMP-binding activity were determined in all subcellular fractions of rat liver. In general, cytosol, microsomal, and lysosomal-mitochondrial cyclic AMP-binding activity was highest in 10-11 day-old rats. Nuclear cyclic AMP-binding activity was highest 3-4 days before birth and declined at birth and during the postnatal period. There was no correlation between the developmental alteration of cyclic AMP-binding activity and cyclic AMP dependency of the protein kinase activity in any of the subcellular fractions. This suggests that the measured cyclic AMP-binding activity does not reflect developmental alterations of the cyclic AMP-binding regulatory subunit of cyclic AMP-dependent protein kinase.", "contents": "Ontogeny of cyclic AMP-dependent protein phosphokinase during hepatic development of the rat. The ontogeny of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) and cyclic AMP-binding activity in subcellular fractions of liver was examined during prenatal and postnatal development of the male rat. 1. Protein kinase activity and cyclic AMP-binding activity were found in the nuclear, microsomal, lysosomal-mitochondrial, and soluble liver fractions. 2. The protein kinase activity of the soluble (105 000 X g supernatant) fraction measured with histone F1 as substrate was stimulated by cyclic AMP. Cyclic AMP did not stimulate the protein kinase activity of the particulate fractions. 3. The protein kinase activity of all subcellular fractions increased rapidly from the activity observed in prenatal liver (3-4 days before birth) to reach maximal activity in 2-day-old rats. Thereafter, the protein kinase activity declined more slowly and regained the prenatal levels at 10 days after birth. 4. Considerable latent protein kinase activity was associated with liver microsomal fractions which could be activated by treatment of microsomes with Triton X-100. The latent microsomal protein kinase activity was highest in prenatal liver, at the time of birth, and 2 days after birth. During the subsequent postnatal development the latent microsomal protein kinase activity gradually declined to insignificantly low levels. 5. During the developmental period examined (4 days before birth to age 60-90 days) marked alterations of the cyclic AMP-binding activity were determined in all subcellular fractions of rat liver. In general, cytosol, microsomal, and lysosomal-mitochondrial cyclic AMP-binding activity was highest in 10-11 day-old rats. Nuclear cyclic AMP-binding activity was highest 3-4 days before birth and declined at birth and during the postnatal period. There was no correlation between the developmental alteration of cyclic AMP-binding activity and cyclic AMP dependency of the protein kinase activity in any of the subcellular fractions. This suggests that the measured cyclic AMP-binding activity does not reflect developmental alterations of the cyclic AMP-binding regulatory subunit of cyclic AMP-dependent protein kinase."} {"id": "PMID:169903", "title": "Effects of cholera toxin on cyclic adenosine 3',5'-monophosphate concentration and secretory processes in the exocrine pancreas.", "content": "1. The effect of purified cholera toxin on secretory processes of exocrine pancreas has been studied in the isolated, saline-perfused cat pancreas and in incubated pieces of rat pancreas. 2. The toxin evoked a biphasic secretory response from the perfused cat pancreas. An initial small phase, which began within minutes of toxin application, was an artefact due to the presence of NaN3 in the cholera toxin preparation as supplied; it could be entirely reproduced by NaN3 at the concentration expected during toxin stimulation. A second, sustained phase of secretion, due to the action of the toxin proper, began within 30-60 min, increasing in magnitude for many hours and persisting in the absence of toxin. It was accompanied by a parellel rise in tissue cyclic AMP concentration, and could be potentiated by theophylline. 3. The composition of the secretion stimulated by cholera toxin resembled that evoked by secretin; e.g. it contained a high concentration of bicarbonate and only basal amounts of digestive enzymes. 4. Similarly, cholera toxin did not stimulate enzyme secretion by incubated rat pancreas, despite large rises in tissue cyclic AMP concentration. 5. Because cholera toxin has thus far been shown to have no other effect than that of stimulating adenylate cyclase, these observations support the conclusion that cyclic AMP does mediate the electrolyte secretory response of the pancreas to secretin, but offers no evidence that cyclic AMP plays a similar role in the regulation of pancreatic enzyme secretion stimulated by cholecystokinin-pancreozymin or acetylcholine.", "contents": "Effects of cholera toxin on cyclic adenosine 3',5'-monophosphate concentration and secretory processes in the exocrine pancreas. 1. The effect of purified cholera toxin on secretory processes of exocrine pancreas has been studied in the isolated, saline-perfused cat pancreas and in incubated pieces of rat pancreas. 2. The toxin evoked a biphasic secretory response from the perfused cat pancreas. An initial small phase, which began within minutes of toxin application, was an artefact due to the presence of NaN3 in the cholera toxin preparation as supplied; it could be entirely reproduced by NaN3 at the concentration expected during toxin stimulation. A second, sustained phase of secretion, due to the action of the toxin proper, began within 30-60 min, increasing in magnitude for many hours and persisting in the absence of toxin. It was accompanied by a parellel rise in tissue cyclic AMP concentration, and could be potentiated by theophylline. 3. The composition of the secretion stimulated by cholera toxin resembled that evoked by secretin; e.g. it contained a high concentration of bicarbonate and only basal amounts of digestive enzymes. 4. Similarly, cholera toxin did not stimulate enzyme secretion by incubated rat pancreas, despite large rises in tissue cyclic AMP concentration. 5. Because cholera toxin has thus far been shown to have no other effect than that of stimulating adenylate cyclase, these observations support the conclusion that cyclic AMP does mediate the electrolyte secretory response of the pancreas to secretin, but offers no evidence that cyclic AMP plays a similar role in the regulation of pancreatic enzyme secretion stimulated by cholecystokinin-pancreozymin or acetylcholine."} {"id": "PMID:169904", "title": "The effect of antiestrogens on egg yolk protein synthesis and estrogen-binding to chromatin in the rooster liver.", "content": "Nafoxidine and CI-628, two well known antiestrogenic compounds, reduce the stimulating effect of estradiol on the estrogen-binding capacity of the liver chromatin from roosters. In vitro both antiestrogens compete with [3H]estradiol for the binding sites on the liver chromatin. They inhibit the estrogen-induced synthesis of egg yolk proteins (vitellogenin) and fail to induce this estrogen-specific protein synthesis by themselves. They show the ability, however, to increase the estrogen-binding sites on the liver chromatin to some extent.", "contents": "The effect of antiestrogens on egg yolk protein synthesis and estrogen-binding to chromatin in the rooster liver. Nafoxidine and CI-628, two well known antiestrogenic compounds, reduce the stimulating effect of estradiol on the estrogen-binding capacity of the liver chromatin from roosters. In vitro both antiestrogens compete with [3H]estradiol for the binding sites on the liver chromatin. They inhibit the estrogen-induced synthesis of egg yolk proteins (vitellogenin) and fail to induce this estrogen-specific protein synthesis by themselves. They show the ability, however, to increase the estrogen-binding sites on the liver chromatin to some extent."} {"id": "PMID:169905", "title": "An analysis of the binding of the chick oviduct progesterone-receptor to chromatin.", "content": "The binding of progesterone-receptor complexes to chromatin from target and nontarget tissues was studied in vitro. Chromatin from both target and nontarget tissues responds in a similar manner to saly and cofactors and has the same K(D) (approx. 3.10(-9) M) for the progesterone-receptor complex. The only observed difference in the binding of the progesterone-receptor complex to target and nontarget chromatins is the difference in total number of acceptor sites. oviduct chromatin has approx. 1300 sites/pg DNA, spleen chromatin has approx. 840 sites/pg DNA, and erythrocyte chromatin has about 330 sites/pg DNA. The K(D) and number of acceptor sites for progesterone-receptor complex binding to oviduct chromatin remains the same even after extensive purification of the progesterone-receptor complex. Activation of cytosol labeled with [3H]progesterone by preincubation at 25 degrees C, analogous to that required for maximal nuclear binding, occurs if the binding studies to chromatin are performed in 0.025 M salt. The absence of an observable temperature effect when the studies are performed at 0.15 M salt is due to the activation of the receptor by salt. The dissociation of the progesterone-receptor complex from chromatin exhibits a single dissociation rate and the initial event is the appearance of free progesterone rather than a progesterone-receptor complex. Lastly, the treatment of chromatin with an antibody prepared against either single-stranded DNA or double-stranded DNA does not alter the extent of binding of the progesterone-receptor complex. Similarly, pretreatment of chromatin with a single-stranded nuclease does not inhibit the capacity of chromatin to bind the hormone-receptor complex.", "contents": "An analysis of the binding of the chick oviduct progesterone-receptor to chromatin. The binding of progesterone-receptor complexes to chromatin from target and nontarget tissues was studied in vitro. Chromatin from both target and nontarget tissues responds in a similar manner to saly and cofactors and has the same K(D) (approx. 3.10(-9) M) for the progesterone-receptor complex. The only observed difference in the binding of the progesterone-receptor complex to target and nontarget chromatins is the difference in total number of acceptor sites. oviduct chromatin has approx. 1300 sites/pg DNA, spleen chromatin has approx. 840 sites/pg DNA, and erythrocyte chromatin has about 330 sites/pg DNA. The K(D) and number of acceptor sites for progesterone-receptor complex binding to oviduct chromatin remains the same even after extensive purification of the progesterone-receptor complex. Activation of cytosol labeled with [3H]progesterone by preincubation at 25 degrees C, analogous to that required for maximal nuclear binding, occurs if the binding studies to chromatin are performed in 0.025 M salt. The absence of an observable temperature effect when the studies are performed at 0.15 M salt is due to the activation of the receptor by salt. The dissociation of the progesterone-receptor complex from chromatin exhibits a single dissociation rate and the initial event is the appearance of free progesterone rather than a progesterone-receptor complex. Lastly, the treatment of chromatin with an antibody prepared against either single-stranded DNA or double-stranded DNA does not alter the extent of binding of the progesterone-receptor complex. Similarly, pretreatment of chromatin with a single-stranded nuclease does not inhibit the capacity of chromatin to bind the hormone-receptor complex."} {"id": "PMID:169906", "title": "Stimulation of sugar transport in rat diaphragm by 8-bromoguanosine 3', 5'-monophosphate.", "content": "The cyclic GMP derivative, 8-bromo cyclic GMP, increases the uptake of D-xylose and of 2-deoxy D-glucose into intact rat diaphragm incubated in vitro. 8-Bromo cyclic GMP does not stimulate the incorporation of [14C]glucose into glycogen in the diaphragm, or the uptake of alphalpha-amino isobutyric acid into this tissue. The effect of 8-bromo cyclic GMP on the diaphragm is consistent with the hypothesis that cyclic GMP plays a role in the regulation of sugar transport in muscle.", "contents": "Stimulation of sugar transport in rat diaphragm by 8-bromoguanosine 3', 5'-monophosphate. The cyclic GMP derivative, 8-bromo cyclic GMP, increases the uptake of D-xylose and of 2-deoxy D-glucose into intact rat diaphragm incubated in vitro. 8-Bromo cyclic GMP does not stimulate the incorporation of [14C]glucose into glycogen in the diaphragm, or the uptake of alphalpha-amino isobutyric acid into this tissue. The effect of 8-bromo cyclic GMP on the diaphragm is consistent with the hypothesis that cyclic GMP plays a role in the regulation of sugar transport in muscle."} {"id": "PMID:169907", "title": "Measurement of particle sizes by elastic and quasi-elastic light scattering.", "content": "A method of measuring an average particle radius in a highly polydisperse dispersion using the wavelength dependence of turbidity is described. For particles which are no larger than 0.3 of the wavelength of light used, a polynomial representation of the scattering cross-section can be used. For larger particles, more extensive numerical calculations are required. The use of the method is illustrated by determining the average particle radius of casein micelles by both elastic and quasi-elastic light scattering techniques. A polydisperse homogeneous sphere model is found to be a reasonably accurate representation of casein micelles. Several modifications of the model which would improve the agreement between the two techniques are mentioned briefly.", "contents": "Measurement of particle sizes by elastic and quasi-elastic light scattering. A method of measuring an average particle radius in a highly polydisperse dispersion using the wavelength dependence of turbidity is described. For particles which are no larger than 0.3 of the wavelength of light used, a polynomial representation of the scattering cross-section can be used. For larger particles, more extensive numerical calculations are required. The use of the method is illustrated by determining the average particle radius of casein micelles by both elastic and quasi-elastic light scattering techniques. A polydisperse homogeneous sphere model is found to be a reasonably accurate representation of casein micelles. Several modifications of the model which would improve the agreement between the two techniques are mentioned briefly."} {"id": "PMID:169908", "title": "Tritiation of endotoxin.", "content": "Tritiated endotoxin was synthesized by three different methods: (1) sodium boro[3H]hydride reduction of native endotoxin; (2) sodium boro[3H]hydride reduction of endotoxin that had been oxidized previously with sodium metaperiodate; and (3) exposure of dry endotoxin to 3H2 gas. Sodium borohydride reduces aldehyde groups and sodium metaperiodate oxidizes vicinal glycol groups to aldehydes. Chromatographic analysis of the three tritiated endotoxins, using agarose, revealed that the biological activity associated with each labeled product appeared at the void volume, and in each case the biological activity coincided with a peak in radioactivity. The labeled product of the first method had a specific radioactivity of 0.18 mCi/g and a biological activity equal to that of native endotoxin. The labeled products of the second and third methods had specific activities of 2.1 mCi/g and 60.0 mCi/g, respectively, while their biological activities were one hundred-fold less than native endotoxin, as determined by the Limulus amebocyte lysate assay. These three labeled endotoxins are potentially ueled endotoxin.", "contents": "Tritiation of endotoxin. Tritiated endotoxin was synthesized by three different methods: (1) sodium boro[3H]hydride reduction of native endotoxin; (2) sodium boro[3H]hydride reduction of endotoxin that had been oxidized previously with sodium metaperiodate; and (3) exposure of dry endotoxin to 3H2 gas. Sodium borohydride reduces aldehyde groups and sodium metaperiodate oxidizes vicinal glycol groups to aldehydes. Chromatographic analysis of the three tritiated endotoxins, using agarose, revealed that the biological activity associated with each labeled product appeared at the void volume, and in each case the biological activity coincided with a peak in radioactivity. The labeled product of the first method had a specific radioactivity of 0.18 mCi/g and a biological activity equal to that of native endotoxin. The labeled products of the second and third methods had specific activities of 2.1 mCi/g and 60.0 mCi/g, respectively, while their biological activities were one hundred-fold less than native endotoxin, as determined by the Limulus amebocyte lysate assay. These three labeled endotoxins are potentially ueled endotoxin."} {"id": "PMID:169909", "title": "Studies on the reconstitution of bovine erythrocyte superoxide dismutase. V. Preparation and properties of derivatives in which both zinc and copper sites contain copper.", "content": "1. We have developed a procedure for preparing derivatives of bovine superoxide dismutase in which primarily the Cu binding sites are occupied by Cu2+ (2 Cu2+-) and in which both the Zn and Cu binding sites are occupied by Cu2+ (4 Cu2+-). 2. The 2 Cu2+ protein shows approximately one-half the superoxide dismutase activity of an equivalent amount of native protein. A two-fold enhancement of the activity of 2 Cu2+-dismutase was observed upon occupation of the Zn sites either with Zn2+ or Cu2+. 3. The electron paramagnetic resonance spectrum of 4 Cu2+ protein was recorded over the temperature range 5-100 degrees K and the results suggest an antiferro-magnetic interaction between Cu2+ in the Zn site and Cu2+ in the Cu site having a coupling constant of approx. 52 cm-1. 4. The binuclear Cu2+ complex was found to accept only one electron from ferrocyanide. 5. One-half the total Cu+ of dithionite reduced 4 Cu+ protein was found to react rapidly with bathocupreine sulfonate whereas the other half reacted slowly. Reduced native protein did not react with bathocupreine sulfonate below 70 degrees C.", "contents": "Studies on the reconstitution of bovine erythrocyte superoxide dismutase. V. Preparation and properties of derivatives in which both zinc and copper sites contain copper. 1. We have developed a procedure for preparing derivatives of bovine superoxide dismutase in which primarily the Cu binding sites are occupied by Cu2+ (2 Cu2+-) and in which both the Zn and Cu binding sites are occupied by Cu2+ (4 Cu2+-). 2. The 2 Cu2+ protein shows approximately one-half the superoxide dismutase activity of an equivalent amount of native protein. A two-fold enhancement of the activity of 2 Cu2+-dismutase was observed upon occupation of the Zn sites either with Zn2+ or Cu2+. 3. The electron paramagnetic resonance spectrum of 4 Cu2+ protein was recorded over the temperature range 5-100 degrees K and the results suggest an antiferro-magnetic interaction between Cu2+ in the Zn site and Cu2+ in the Cu site having a coupling constant of approx. 52 cm-1. 4. The binuclear Cu2+ complex was found to accept only one electron from ferrocyanide. 5. One-half the total Cu+ of dithionite reduced 4 Cu+ protein was found to react rapidly with bathocupreine sulfonate whereas the other half reacted slowly. Reduced native protein did not react with bathocupreine sulfonate below 70 degrees C."} {"id": "PMID:169910", "title": "Regulation of GMP reductase in Salmonella typhimurium.", "content": "The levels of guanosine 5'-phosphate reductase (EC 1.6.6.8) in Salmonella typhimurium appear to be modulated by changes in the ratio of the adenine and guanine nucleotide pools. Alterations of this ratio may be induced by high levels of guanosine in the culture medium or by genetic lesions in one of several purine interconversion enzymes, such as pur A or pur B mutants. The induction of the reductase requires transcription and translation processes and, in contrast to earlier observation with Escherichia coli, is not dependent on cyclic adenosine 3',5'-phosphate or the cyclic adenosine 3',5'-phosphate receptor protein.", "contents": "Regulation of GMP reductase in Salmonella typhimurium. The levels of guanosine 5'-phosphate reductase (EC 1.6.6.8) in Salmonella typhimurium appear to be modulated by changes in the ratio of the adenine and guanine nucleotide pools. Alterations of this ratio may be induced by high levels of guanosine in the culture medium or by genetic lesions in one of several purine interconversion enzymes, such as pur A or pur B mutants. The induction of the reductase requires transcription and translation processes and, in contrast to earlier observation with Escherichia coli, is not dependent on cyclic adenosine 3',5'-phosphate or the cyclic adenosine 3',5'-phosphate receptor protein."} {"id": "PMID:169911", "title": "Studies of a halophilic NADH dehydrogenase. II. Kinetic properties of the enzyme in relation to salt activation.", "content": "1. An NADH dehydrogenase, obtained from an extremely halophilic bacterium, was activated by various salts when enzyme activity was measured as the observed velocity, whereas the maximum velocity was unaffected by either the salt concentration or the nature of the salt. 2. Two ion effects were observed; a quantitative cation effect, reflected in changes in the apparent Michaelis constant for 2,6-dichlorophenolindophenol, and a qualitative anion effect, reflected in the apparent Michaelis and dissociation constants for NADH. 3. The data suggest that cations act by neutralizing electrostatic charges surrounding the 2,6-dichlorophenolindophenol-binding site, whereas the anions affect the conformation of the enzyme by altering the accessibility of the NADH-binding site to the bulk solvent. 4. Thus, the apparent activation of this enzyme, obtained from an extremely halophilic bacterium, is a reflection of measuring enzyme activity at non-saturating substrate concentrations.", "contents": "Studies of a halophilic NADH dehydrogenase. II. Kinetic properties of the enzyme in relation to salt activation. 1. An NADH dehydrogenase, obtained from an extremely halophilic bacterium, was activated by various salts when enzyme activity was measured as the observed velocity, whereas the maximum velocity was unaffected by either the salt concentration or the nature of the salt. 2. Two ion effects were observed; a quantitative cation effect, reflected in changes in the apparent Michaelis constant for 2,6-dichlorophenolindophenol, and a qualitative anion effect, reflected in the apparent Michaelis and dissociation constants for NADH. 3. The data suggest that cations act by neutralizing electrostatic charges surrounding the 2,6-dichlorophenolindophenol-binding site, whereas the anions affect the conformation of the enzyme by altering the accessibility of the NADH-binding site to the bulk solvent. 4. Thus, the apparent activation of this enzyme, obtained from an extremely halophilic bacterium, is a reflection of measuring enzyme activity at non-saturating substrate concentrations."} {"id": "PMID:169912", "title": "Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells.", "content": "In continuing our study of the thyroidal autoregulation phenomenon, we have investigated the effects of iodide on several thyroidal responses to thyrotropin. Thus, we have found that the 2--4-fold thyrotropin stimulation of protein iodination in beef thyroid cells was reduced about 30% by 4 h of preincubation with 10 muM iodide, and virtually abolished with 50 muM iodide. Similarly the 8-fold thyrotropin stimulation of cyclic AMP accumulation in the cells was reduced about 30% by 3 h of preincubation with 50 muM iodide. It appears therefore that the so-called autoregulation of the thyroid gland does include influences of iodide on the thyrotropin stimulation of cyclic AMP production, iodide transport, and protein iodination which can be demonstrated in vitro in the dispersed thyroid cell system. Two other effects of thyrotropin, namely, the stimulation of [14C]leucine incorporation into protein and of iodide efflux were not at all affected by treatment with excess iodide, and hence may not be subject to the autoregulatory influence of iodide.", "contents": "Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells. In continuing our study of the thyroidal autoregulation phenomenon, we have investigated the effects of iodide on several thyroidal responses to thyrotropin. Thus, we have found that the 2--4-fold thyrotropin stimulation of protein iodination in beef thyroid cells was reduced about 30% by 4 h of preincubation with 10 muM iodide, and virtually abolished with 50 muM iodide. Similarly the 8-fold thyrotropin stimulation of cyclic AMP accumulation in the cells was reduced about 30% by 3 h of preincubation with 50 muM iodide. It appears therefore that the so-called autoregulation of the thyroid gland does include influences of iodide on the thyrotropin stimulation of cyclic AMP production, iodide transport, and protein iodination which can be demonstrated in vitro in the dispersed thyroid cell system. Two other effects of thyrotropin, namely, the stimulation of [14C]leucine incorporation into protein and of iodide efflux were not at all affected by treatment with excess iodide, and hence may not be subject to the autoregulatory influence of iodide."} {"id": "PMID:169913", "title": "Intracellular formation of analogs of cyclic AMP. Studies with brain slices labeled with radioactive derivatives of adenine and adenosine.", "content": "A variety of radioactive analogs of adenine and adenosine were incubated with guinea pig cerebral cortical slices. Neither 1,N6-etheno[14C] adenosine nor 1,N6-etheno[14C] adenine were significantly incorporated into intracellular nucleotides. 2-chloro[8-3H] adenine was incorporated, but at a very low rate and conclusive evidence for the formation of intracellular radioactive 2-chloro-cyclic AMP was not obtained. N6-Benzyl[14C] adenosine was converted only to intracellular monophosphates and significant formation of radioactive N6-benzylcyclic AMP was not detected during a subsequent incubation. 2'-Deoxy-[8-14C] adenosine was converted to both intracellular radioactive 2'-deoxy-adenine nucleotides and radioactive adenine nucleotides. Stimulation of these labeled slices with a variety of agents resulted in formation of both radioactive 2'-deoxycyclic AMP and cyclic AMP. Investigation of the effect of various other compounds on uptake of adenine or adenosine suggested that certain other adenosine analogs might serve as precursors of abnormal cyclic nucleotides in intact cells.", "contents": "Intracellular formation of analogs of cyclic AMP. Studies with brain slices labeled with radioactive derivatives of adenine and adenosine. A variety of radioactive analogs of adenine and adenosine were incubated with guinea pig cerebral cortical slices. Neither 1,N6-etheno[14C] adenosine nor 1,N6-etheno[14C] adenine were significantly incorporated into intracellular nucleotides. 2-chloro[8-3H] adenine was incorporated, but at a very low rate and conclusive evidence for the formation of intracellular radioactive 2-chloro-cyclic AMP was not obtained. N6-Benzyl[14C] adenosine was converted only to intracellular monophosphates and significant formation of radioactive N6-benzylcyclic AMP was not detected during a subsequent incubation. 2'-Deoxy-[8-14C] adenosine was converted to both intracellular radioactive 2'-deoxy-adenine nucleotides and radioactive adenine nucleotides. Stimulation of these labeled slices with a variety of agents resulted in formation of both radioactive 2'-deoxycyclic AMP and cyclic AMP. Investigation of the effect of various other compounds on uptake of adenine or adenosine suggested that certain other adenosine analogs might serve as precursors of abnormal cyclic nucleotides in intact cells."} {"id": "PMID:169914", "title": "The effect of temperature on the spectroscopic properties of the heme c octapeptide from cytochrome c.", "content": "The effect of temperature on the optical properties of the acetylated heme c octapeptide from cytochrome c was examined. At above ambient temperatures the observed optical spectrum with maxima at 549 and 424 nm was characteristic of high-spin ferrous hemeproteins. At below ambient temperatures the optical spectrum became characteristic of low-spin ferrous hemeproteins with maxima at 547, 518, and 410 nm. A thermodynamic characterization of this two component system yielded a deltaHO of -10.1 +/- 0.7 kcal/mol and a delta S0 of-37.6 +/- 2.5 e.u. for the temperature dependent process. Discussion of the spectroscopic and thermodynamic parameters was presented in terms of the consistent magnetic and structural properties of heme complexes.", "contents": "The effect of temperature on the spectroscopic properties of the heme c octapeptide from cytochrome c. The effect of temperature on the optical properties of the acetylated heme c octapeptide from cytochrome c was examined. At above ambient temperatures the observed optical spectrum with maxima at 549 and 424 nm was characteristic of high-spin ferrous hemeproteins. At below ambient temperatures the optical spectrum became characteristic of low-spin ferrous hemeproteins with maxima at 547, 518, and 410 nm. A thermodynamic characterization of this two component system yielded a deltaHO of -10.1 +/- 0.7 kcal/mol and a delta S0 of-37.6 +/- 2.5 e.u. for the temperature dependent process. Discussion of the spectroscopic and thermodynamic parameters was presented in terms of the consistent magnetic and structural properties of heme complexes."} {"id": "PMID:169915", "title": "Organization of phospholipids in human red cell membranes as detected by the action of various purified phospholipases.", "content": "1. The action of eight purified phospholipases on intact human erythrocytes has been investigated. Four enzymes, e.g. phospholipases A2 from pancreas and Crotalus adamanteus, phospholipase C from Bacillus cereus, and phospholipase D from cabbage produce neither haemolysis nor hydrolysis of phospholipids in intact cells. On the other hand, both phospholipases A2 from bee venom and Naja naja cause a non-haemolytic breakdown of more than 50% of the lecithin, while sphingomyelinase C from Staphylococcus aureus is able to produce a non-lytic degradation of more than 80% of the sphingomyelin. 2. Phospholipase C from Clostridium welchii appeared to be the only lipolytic enzyme tested, which produces haemolysis of human erythrocytes. Evidence is presented that the unique properties of the enzyme itself, rather than possible contaminations in the purified preparation, are responsible for the observed haemolytic effect. 3. With non-sealed ghosts, all phospholipases produce essentially complete breakdown of those phospholipids which can be considered as proper substrates for the enzymes involved. 4. Due to its absolute requirement for Ca2+, pancreatic phospholipase A2 can be trapped inside resealed ghosts in the presence of EDTA, without producing phospholipid breakdown during the resealing procedure. Subsequent addition of Ca2+ stimulates phospholipase A2 activity at the inside of the resealed cell, eventually leading to lysis. Before lysis occurs, however, 25% of the lecithin, half of the phosphatidylethanolamine and some 65% of the phosphatidylserine can be hydrolysed. This observation is explained in relation to an asymmetric phospholipid distribution in red cell membranes.", "contents": "Organization of phospholipids in human red cell membranes as detected by the action of various purified phospholipases. 1. The action of eight purified phospholipases on intact human erythrocytes has been investigated. Four enzymes, e.g. phospholipases A2 from pancreas and Crotalus adamanteus, phospholipase C from Bacillus cereus, and phospholipase D from cabbage produce neither haemolysis nor hydrolysis of phospholipids in intact cells. On the other hand, both phospholipases A2 from bee venom and Naja naja cause a non-haemolytic breakdown of more than 50% of the lecithin, while sphingomyelinase C from Staphylococcus aureus is able to produce a non-lytic degradation of more than 80% of the sphingomyelin. 2. Phospholipase C from Clostridium welchii appeared to be the only lipolytic enzyme tested, which produces haemolysis of human erythrocytes. Evidence is presented that the unique properties of the enzyme itself, rather than possible contaminations in the purified preparation, are responsible for the observed haemolytic effect. 3. With non-sealed ghosts, all phospholipases produce essentially complete breakdown of those phospholipids which can be considered as proper substrates for the enzymes involved. 4. Due to its absolute requirement for Ca2+, pancreatic phospholipase A2 can be trapped inside resealed ghosts in the presence of EDTA, without producing phospholipid breakdown during the resealing procedure. Subsequent addition of Ca2+ stimulates phospholipase A2 activity at the inside of the resealed cell, eventually leading to lysis. Before lysis occurs, however, 25% of the lecithin, half of the phosphatidylethanolamine and some 65% of the phosphatidylserine can be hydrolysed. This observation is explained in relation to an asymmetric phospholipid distribution in red cell membranes."} {"id": "PMID:169916", "title": "Further purification of \"Triton subchloroplast fraction I\" (TSF-I particles). Isolation of a cytochrome-free high-P-700 particle and a complex containing cytochromes f and b6, plastocyanin and iron-sulfur protein(s).", "content": "The \"Triton Subchloroplast Fraction I\" or \"TSF-I particles\" can be further fractionated into a cytochrome fraction and a P-700-containing fraction essentially free of cytochromes. The cytochrome complex contains cytochromes f and b6 in approx. equimolar amounts, and, in addition, also plastocyanin and one iron-sulfur protein, all in the bound state. Bound plastocyanin was characterized by EPR spectroscopy. The EPR spectrum of the bound iron-sulfur protein resembles that previously detected in Phostosystem I particles under highly reducing conditions at lower than -560 mV. The redox potential of P-700 in the cytochrome-free high-P-700 particles was measured to be +468 mV; those of cytochromes f and b6 are +345 and -140 mV, respectively. Among the four components present in the complex, only cytochrome f can be coupled to a Photosystem I particle and undergoes photooxidation. This coupled photooxidation is totoally inhibited by KCN and only partially inhibited by HgCl2. The similarity of the complex containing cytochromes f and b6, plastocyanin, and an iron-sulfur protein to complexes III and IV of the mitochondrial respiratory redox chain and a possible involvement of the complex in cyclic photophosphorylation are noted and discussed.", "contents": "Further purification of \"Triton subchloroplast fraction I\" (TSF-I particles). Isolation of a cytochrome-free high-P-700 particle and a complex containing cytochromes f and b6, plastocyanin and iron-sulfur protein(s). The \"Triton Subchloroplast Fraction I\" or \"TSF-I particles\" can be further fractionated into a cytochrome fraction and a P-700-containing fraction essentially free of cytochromes. The cytochrome complex contains cytochromes f and b6 in approx. equimolar amounts, and, in addition, also plastocyanin and one iron-sulfur protein, all in the bound state. Bound plastocyanin was characterized by EPR spectroscopy. The EPR spectrum of the bound iron-sulfur protein resembles that previously detected in Phostosystem I particles under highly reducing conditions at lower than -560 mV. The redox potential of P-700 in the cytochrome-free high-P-700 particles was measured to be +468 mV; those of cytochromes f and b6 are +345 and -140 mV, respectively. Among the four components present in the complex, only cytochrome f can be coupled to a Photosystem I particle and undergoes photooxidation. This coupled photooxidation is totoally inhibited by KCN and only partially inhibited by HgCl2. The similarity of the complex containing cytochromes f and b6, plastocyanin, and an iron-sulfur protein to complexes III and IV of the mitochondrial respiratory redox chain and a possible involvement of the complex in cyclic photophosphorylation are noted and discussed."} {"id": "PMID:169919", "title": "EEG and neurophysiological studies of early infantile autism.", "content": "My aims in this presentation are to review EEG findings that have been published recently in children variously labeled as autistic, schizophrenic, or psychotic. I will also report new results from EEG investigations of an expanded series of Dr. DeMyer's subjects. Sleep research and studies of cerebral evoked responses and the contingent negative variation will be reviewed, and preliminary results of wuantitative analyses of EEG from autistic and normal children will be reported.", "contents": "EEG and neurophysiological studies of early infantile autism. My aims in this presentation are to review EEG findings that have been published recently in children variously labeled as autistic, schizophrenic, or psychotic. I will also report new results from EEG investigations of an expanded series of Dr. DeMyer's subjects. Sleep research and studies of cerebral evoked responses and the contingent negative variation will be reviewed, and preliminary results of wuantitative analyses of EEG from autistic and normal children will be reported."} {"id": "PMID:169920", "title": "Serotonin inhibition and sleep.", "content": "Methysergide a clinically used blocker of serotonin receptors, was given for 48 hr to 11 normal adults, at a dose of 8 mg per 24 hr. Total REM sleep time was decreased, although total sleep time was unchanged. Stage 4 decreased and stage 3 increased, while total slow wave sleep remained constant. There was a tendency toward a decrease in the number of intact sleep cycles. The relationship of these data to published reports on p-chlorophenylalanine is discussed.", "contents": "Serotonin inhibition and sleep. Methysergide a clinically used blocker of serotonin receptors, was given for 48 hr to 11 normal adults, at a dose of 8 mg per 24 hr. Total REM sleep time was decreased, although total sleep time was unchanged. Stage 4 decreased and stage 3 increased, while total slow wave sleep remained constant. There was a tendency toward a decrease in the number of intact sleep cycles. The relationship of these data to published reports on p-chlorophenylalanine is discussed."} {"id": "PMID:169921", "title": "Hypnosis and eye movements.", "content": "Eye movements (with closed lids) were studied in a group of highly hypnotizable experimental subjects experienced in self-hypnosis, and compared with a random sample of control subjects that had never been hypnotized and were low in waking suggestibility. Approximately half the experimental subjects rolled their eyes upwards to a greater extent when hypnosis was induced than during eye closure while awake. In some subjects eye flutter occurred during hypnosis, but not in the awake condition. During passive hypnosis the mean rates of rapid eye movements were lower, but those of slow eye movements were higher than during the resting awake condition of the same subjects or the random control subjects. The mean rates of horizontal eye movements during suggestions about begin in a train and watching passing telephone poles were higher for the experimental subjects in the hypnosis and 'imagination' sessions than that of the random control group in the imagination session. A proportion of the experimental subjects made more lateral eye movements during hypnosis than during the imagination session, but an equal proportion did not differ between the two conditions. The mean rates and durations of horizontal eye movements during dreaming about a tennis match were greater during hypnosis ('hypnotic' dream), than during the awake condition a few minutes later ('natural' dream), or the awake condition in the imagination session ('imagination' dream) of the same subjects or random controls. The performance and subjective involvement of the experimental subjects during the Barber suggestibility scale, 'nystagmus' suggestions and 'dreaming' did not differ significantly between the two hypnosis sessions, but in most cases were significantly greater during hypnosis than during the imagination session of the same group or the random control group.", "contents": "Hypnosis and eye movements. Eye movements (with closed lids) were studied in a group of highly hypnotizable experimental subjects experienced in self-hypnosis, and compared with a random sample of control subjects that had never been hypnotized and were low in waking suggestibility. Approximately half the experimental subjects rolled their eyes upwards to a greater extent when hypnosis was induced than during eye closure while awake. In some subjects eye flutter occurred during hypnosis, but not in the awake condition. During passive hypnosis the mean rates of rapid eye movements were lower, but those of slow eye movements were higher than during the resting awake condition of the same subjects or the random control subjects. The mean rates of horizontal eye movements during suggestions about begin in a train and watching passing telephone poles were higher for the experimental subjects in the hypnosis and 'imagination' sessions than that of the random control group in the imagination session. A proportion of the experimental subjects made more lateral eye movements during hypnosis than during the imagination session, but an equal proportion did not differ between the two conditions. The mean rates and durations of horizontal eye movements during dreaming about a tennis match were greater during hypnosis ('hypnotic' dream), than during the awake condition a few minutes later ('natural' dream), or the awake condition in the imagination session ('imagination' dream) of the same subjects or random controls. The performance and subjective involvement of the experimental subjects during the Barber suggestibility scale, 'nystagmus' suggestions and 'dreaming' did not differ significantly between the two hypnosis sessions, but in most cases were significantly greater during hypnosis than during the imagination session of the same group or the random control group."} {"id": "PMID:169923", "title": "The hepatic chalone. II. Chemical and biological properties of the rabbit liver chalone.", "content": "A factor has been purified from rabbit liver which decreases the incorporation of 3H-thymidine in DNA of regenerating rat liver slices. This effect is due mostly to an inhibition of DNA synthesis from the deoxynucleoside triphosphates. The purified rabbit liver factor thus interferes with the liver cell division cycle. This inhibitor of DNA synthesis is specific for liver cells; it is not toxic for cultured hepatocytes and its action on DNA synthesis is reversible: at low dose, the inhibition of DNA synthesis in regenerating liver slices is transitory. The purified rabbit liver inhibitor is thus a chalone. The purified rabbit liver chalone ultrafiltrates through 1.2 nm pores, is destroyed by trypsine and pronase, carries a negative charge at pH 8.8 and a positive charge at pH 4.6; it is thermostable and likely a small peptide. It also inhibits RNA and protein synthesis in regenerating liver slices. The inhibition of protein synthesis is immediately maximal then decreases with time, while the maximum inhibition of DNA and RNA synthesis appears after a delay. When a low dose of chalone is used (0.2 unit per 5 ml), the inhibition of DNA and RNA synthesis disappears after some time: this is not due to a destruction of the chalone, but to a loss of sensitivity of the slices incubated in Hanks solution. The inhibitor content of liver cells, normal or malignant, seems inversely correlated with their state of growth. It is much lower in the liver of a young animal or in regenerating liver than in adult liver. Hepatomas produced by feeding DAB contain three times less inhibitor than the normal liver. The purified liver chalone is 5-10 times less active on the incorporation of 3H-thymidine in DNA of DAB hepatoma slices than in DNA of regenerating liver slices. It has no apparent action on adult liver slices; this might be due to the fact that 3H-thymidine incorporation into DNA of the adult organ depends, for the greater part, on other processes than DNA replication in hepatocytes.", "contents": "The hepatic chalone. II. Chemical and biological properties of the rabbit liver chalone. A factor has been purified from rabbit liver which decreases the incorporation of 3H-thymidine in DNA of regenerating rat liver slices. This effect is due mostly to an inhibition of DNA synthesis from the deoxynucleoside triphosphates. The purified rabbit liver factor thus interferes with the liver cell division cycle. This inhibitor of DNA synthesis is specific for liver cells; it is not toxic for cultured hepatocytes and its action on DNA synthesis is reversible: at low dose, the inhibition of DNA synthesis in regenerating liver slices is transitory. The purified rabbit liver inhibitor is thus a chalone. The purified rabbit liver chalone ultrafiltrates through 1.2 nm pores, is destroyed by trypsine and pronase, carries a negative charge at pH 8.8 and a positive charge at pH 4.6; it is thermostable and likely a small peptide. It also inhibits RNA and protein synthesis in regenerating liver slices. The inhibition of protein synthesis is immediately maximal then decreases with time, while the maximum inhibition of DNA and RNA synthesis appears after a delay. When a low dose of chalone is used (0.2 unit per 5 ml), the inhibition of DNA and RNA synthesis disappears after some time: this is not due to a destruction of the chalone, but to a loss of sensitivity of the slices incubated in Hanks solution. The inhibitor content of liver cells, normal or malignant, seems inversely correlated with their state of growth. It is much lower in the liver of a young animal or in regenerating liver than in adult liver. Hepatomas produced by feeding DAB contain three times less inhibitor than the normal liver. The purified liver chalone is 5-10 times less active on the incorporation of 3H-thymidine in DNA of DAB hepatoma slices than in DNA of regenerating liver slices. It has no apparent action on adult liver slices; this might be due to the fact that 3H-thymidine incorporation into DNA of the adult organ depends, for the greater part, on other processes than DNA replication in hepatocytes."} {"id": "PMID:169924", "title": "Lp (a) blood types. Comparison of immunological testing with results of polyacrylamide gel electrophoresis.", "content": "The results of serum beta-lipoproteins typing of 100 random human sera for Lp (a) antigen by the standard immunological method were compared with those of polyacrylamide gel electrophoresis which may detect an Lp (a) band migrating more slowly than the bulk of LDL. This band was found in all the 33 Lp (a+) but also in 9 of the 67 Lp (a-) sera examined.", "contents": "Lp (a) blood types. Comparison of immunological testing with results of polyacrylamide gel electrophoresis. The results of serum beta-lipoproteins typing of 100 random human sera for Lp (a) antigen by the standard immunological method were compared with those of polyacrylamide gel electrophoresis which may detect an Lp (a) band migrating more slowly than the bulk of LDL. This band was found in all the 33 Lp (a+) but also in 9 of the 67 Lp (a-) sera examined."} {"id": "PMID:169925", "title": "Axon voltage-clamp simulations. III. Postsynaptic region.", "content": "This is the third in a series of four papers in which we present the numerical simulations of the application of the voltage clamp technique to excitable cells. In this paper we discuss the problem of voltage clamping a region of a cylindrical cell using microelectrodes for current injection and voltage recording. A recently developed technique (Llin\u00e1s et al., 1974) of internal application of oil drops to electrically insulate a short length of the postsynaptic region of the squid giant synapse is evaluated by simulation of the voltage clamp of an excitable cylindrical cell of finite length with variable placement of the current and voltage electrodes. Our results show that ENa can be determined quite accurately with feasible oil gap lengths but that the determination of the reversal potential for the synaptic conductance, ES, can be considerably in error. The error in the determination of ES dependp, and especially the membrane resistance at the time the synaptic conductance occurs. It is shown that the application of tetraethylammonium chloride to block the active potassium conductance very significantly reduces the error in the determination of ES. In addition we discuss the effects of cable length and electrode position on the apparent amplitude and time course of the syn aptic conductance change. These results are particularly relevant to the application of the voltage clamp technique to cells with nonsomatic synapses. The method of simulation presented here provides a tool for evaluation of voltage clamp analysis of synaptic transmission for any cell with known membrane parameters and geometry.", "contents": "Axon voltage-clamp simulations. III. Postsynaptic region. This is the third in a series of four papers in which we present the numerical simulations of the application of the voltage clamp technique to excitable cells. In this paper we discuss the problem of voltage clamping a region of a cylindrical cell using microelectrodes for current injection and voltage recording. A recently developed technique (Llin\u00e1s et al., 1974) of internal application of oil drops to electrically insulate a short length of the postsynaptic region of the squid giant synapse is evaluated by simulation of the voltage clamp of an excitable cylindrical cell of finite length with variable placement of the current and voltage electrodes. Our results show that ENa can be determined quite accurately with feasible oil gap lengths but that the determination of the reversal potential for the synaptic conductance, ES, can be considerably in error. The error in the determination of ES dependp, and especially the membrane resistance at the time the synaptic conductance occurs. It is shown that the application of tetraethylammonium chloride to block the active potassium conductance very significantly reduces the error in the determination of ES. In addition we discuss the effects of cable length and electrode position on the apparent amplitude and time course of the syn aptic conductance change. These results are particularly relevant to the application of the voltage clamp technique to cells with nonsomatic synapses. The method of simulation presented here provides a tool for evaluation of voltage clamp analysis of synaptic transmission for any cell with known membrane parameters and geometry."} {"id": "PMID:169926", "title": "A proton-relaxation enhancement study of the interaction of manganous ions with phospholipids in aqueous dispersions.", "content": "An interaction of dipalmitoylphosphatidylcholine (PC) and phosphatidylserine (PS) with manganous ions has been investigated by measuring the effect of bound manganese upon the longitudinal relaxation rate, 1/T1, of the solvent water protons and evaluating the enhancement factor epsilon b. The observed enhancement values were used to determine the number of interacting sites per polar head group, n, and the values of association constants, KA, of manganese to PC and PS. Changes in epsilon b correlate with structural changes at the interacting site. By increasing the temperature one can see an abrupt decrease in epsilon b within the temperature interval from 40 to 50 degrees C indicating the thermal phase transition of PC as established by calorimetry, fluorescence and high-resolution NMR measurements. That an enhancement of 1/T1 of the solvent-water protons occurs at all is explained by assuming a restricted rotation of the Mn2+-aquo complex in the bound state. In addition we suppose that the rotation of the Mn2+-aquo complex is the mechanism which dominates the relaxation of the water protons in teh bulk solvent when phospholipids are present.", "contents": "A proton-relaxation enhancement study of the interaction of manganous ions with phospholipids in aqueous dispersions. An interaction of dipalmitoylphosphatidylcholine (PC) and phosphatidylserine (PS) with manganous ions has been investigated by measuring the effect of bound manganese upon the longitudinal relaxation rate, 1/T1, of the solvent water protons and evaluating the enhancement factor epsilon b. The observed enhancement values were used to determine the number of interacting sites per polar head group, n, and the values of association constants, KA, of manganese to PC and PS. Changes in epsilon b correlate with structural changes at the interacting site. By increasing the temperature one can see an abrupt decrease in epsilon b within the temperature interval from 40 to 50 degrees C indicating the thermal phase transition of PC as established by calorimetry, fluorescence and high-resolution NMR measurements. That an enhancement of 1/T1 of the solvent-water protons occurs at all is explained by assuming a restricted rotation of the Mn2+-aquo complex in the bound state. In addition we suppose that the rotation of the Mn2+-aquo complex is the mechanism which dominates the relaxation of the water protons in teh bulk solvent when phospholipids are present."} {"id": "PMID:169927", "title": "Effect of DNA base composition on the intercalation of proflavine. A kinetic study.", "content": "The effect of DNA base composition on the kinetics of the association between DNA and proflavine has been investigated using the temperature jump relaxation method. It is found that, regardless of the G + C base composition the results fit a two step mechanism, the second of which exhibits characteristics of intercalation of proflavine into DNA. However, they two equilibrium constants corresponding to these steps, KI and KII, depend on the nature of the DNAs. The constant KI is found to be an order of magnitude greater for M. lysodeikticus DNA (72% G + C) than for calf thymus DNA (48% G + C). Increasing G-C content thus appears to favor the intermediate non-intercalated complex of proflavine with DNA. Methylation of M. lysodeikticus DNA with dimethyl sulfate, preferentially yielding N7 methyl guanine as the modified base, again leads to an apparent two step mechanism, with the value of KI unchanged with respect to untreated DNA, while the affinity of proflavine for the intercalated complex measured by the value of KII increases for methylated DNA.", "contents": "Effect of DNA base composition on the intercalation of proflavine. A kinetic study. The effect of DNA base composition on the kinetics of the association between DNA and proflavine has been investigated using the temperature jump relaxation method. It is found that, regardless of the G + C base composition the results fit a two step mechanism, the second of which exhibits characteristics of intercalation of proflavine into DNA. However, they two equilibrium constants corresponding to these steps, KI and KII, depend on the nature of the DNAs. The constant KI is found to be an order of magnitude greater for M. lysodeikticus DNA (72% G + C) than for calf thymus DNA (48% G + C). Increasing G-C content thus appears to favor the intermediate non-intercalated complex of proflavine with DNA. Methylation of M. lysodeikticus DNA with dimethyl sulfate, preferentially yielding N7 methyl guanine as the modified base, again leads to an apparent two step mechanism, with the value of KI unchanged with respect to untreated DNA, while the affinity of proflavine for the intercalated complex measured by the value of KII increases for methylated DNA."} {"id": "PMID:169929", "title": "Acute monoblastic leukemia: diagnosis and treatment of ten cases.", "content": "During a large clinicopathologic study of acute nonlymphocytic leukemia (ANLL), ten patients were identified in whom the leukemic blasts demonstrated striking morphologic and cytochemical similarities and who seemed to form a specific subgroup of ANLL. The patients' leukemic blasts were studied in routine blood and bone marrow preparations and by cytochemical and ultrastructural techniques. In routine smears, the blasts showed no clear evidence of differentiation. Cytochemically, the blasts exhibited strongly positive nonspecific esterase activity, which was completely inhibited by incubation with sodium fluoride, and were myeloperoxidase and sudan black B negative. Ultrastructural features of the blasts were similar to those described for monocytic leukemias. Striking clinical features included the occurrence primarily in young patients, the high frequency of lymphadenopathy at presentation, and the high incidence of post-treatment disseminated intravascular coagulation. Complete remissions were frequently initially obtained with duanorubicin in combination with various other agents and later in the disease with VP16-213. Based on the cytochemical and ultrastructural features, we concluded that this form of ANLL was a variety of acute monocytic leukemia. Recognition of the entity is important for optimal therapy.", "contents": "Acute monoblastic leukemia: diagnosis and treatment of ten cases. During a large clinicopathologic study of acute nonlymphocytic leukemia (ANLL), ten patients were identified in whom the leukemic blasts demonstrated striking morphologic and cytochemical similarities and who seemed to form a specific subgroup of ANLL. The patients' leukemic blasts were studied in routine blood and bone marrow preparations and by cytochemical and ultrastructural techniques. In routine smears, the blasts showed no clear evidence of differentiation. Cytochemically, the blasts exhibited strongly positive nonspecific esterase activity, which was completely inhibited by incubation with sodium fluoride, and were myeloperoxidase and sudan black B negative. Ultrastructural features of the blasts were similar to those described for monocytic leukemias. Striking clinical features included the occurrence primarily in young patients, the high frequency of lymphadenopathy at presentation, and the high incidence of post-treatment disseminated intravascular coagulation. Complete remissions were frequently initially obtained with duanorubicin in combination with various other agents and later in the disease with VP16-213. Based on the cytochemical and ultrastructural features, we concluded that this form of ANLL was a variety of acute monocytic leukemia. Recognition of the entity is important for optimal therapy."} {"id": "PMID:169931", "title": "The effects of tetraphenylboron on neuromuscular transmission in the frog.", "content": "1 The effect of tetraphenylboron (TPB) were studied on the frog sciatic nerve-sartorius muscle preparation. 2 TPB (0.01-1 mM) blocked indirectly elicited twitches of the preparation. 3 TPB (0.01-0.1 mM) produced no depolarization but lowered membrane resistance. TPB increased miniature endplate potential (m.e.p.p.) frequency, the rate of rise of the endplate potential (e.p.p.), and slowed the rate of rise and rate of fall of the muscle action potential. 4 In Mg2+ solutions the quantal content of e.p.ps was initially increased by TPB (0.01 mM). This was followed by a decrease of e.p.p. and m.e.p.p. amplitudes, accompanied by a lack of e.p.p. failures. 5 Larger concentrations of TPB (0.1 mM) produced an increase in e.p.p. amplitude followed by the sudden abolition of e.p.ps. This effect was associated with abolition of the nerve terminal spike. 6 TPB (0.1 mM) exhibited no postjunctional blocking action. 7 The results indicate that TPB acts prejunctionally, initially causing an increased release of acetylcholine. Subsequently, transmitter output is reduced by a reduction of quantal size.", "contents": "The effects of tetraphenylboron on neuromuscular transmission in the frog. 1 The effect of tetraphenylboron (TPB) were studied on the frog sciatic nerve-sartorius muscle preparation. 2 TPB (0.01-1 mM) blocked indirectly elicited twitches of the preparation. 3 TPB (0.01-0.1 mM) produced no depolarization but lowered membrane resistance. TPB increased miniature endplate potential (m.e.p.p.) frequency, the rate of rise of the endplate potential (e.p.p.), and slowed the rate of rise and rate of fall of the muscle action potential. 4 In Mg2+ solutions the quantal content of e.p.ps was initially increased by TPB (0.01 mM). This was followed by a decrease of e.p.p. and m.e.p.p. amplitudes, accompanied by a lack of e.p.p. failures. 5 Larger concentrations of TPB (0.1 mM) produced an increase in e.p.p. amplitude followed by the sudden abolition of e.p.ps. This effect was associated with abolition of the nerve terminal spike. 6 TPB (0.1 mM) exhibited no postjunctional blocking action. 7 The results indicate that TPB acts prejunctionally, initially causing an increased release of acetylcholine. Subsequently, transmitter output is reduced by a reduction of quantal size."} {"id": "PMID:169932", "title": "An inhibitory effect of atropine on responses of the vas deferens of the mouse to field stimulation.", "content": "1 Atropine is shown to impair responses of the vas deferens of the mouse to field stimulation by acting at a site proximal to the smooth muscle cells. 2 The inhibitory effect of atropine is prevented by desmethylimipramine and reversed by dexamphetamine, and appears similar to the adrenergic-neurone blockade of guanethidine. 3 Electronmicroscopical studies show the presence in vas of presumptive noradrenergic axons which have acetylcholinesterase reaction product associated with their axolemmae. 4 These results are discussed in relation to the controversial hypothesis of a 'cholinergic link' in noradrenergic transmission.", "contents": "An inhibitory effect of atropine on responses of the vas deferens of the mouse to field stimulation. 1 Atropine is shown to impair responses of the vas deferens of the mouse to field stimulation by acting at a site proximal to the smooth muscle cells. 2 The inhibitory effect of atropine is prevented by desmethylimipramine and reversed by dexamphetamine, and appears similar to the adrenergic-neurone blockade of guanethidine. 3 Electronmicroscopical studies show the presence in vas of presumptive noradrenergic axons which have acetylcholinesterase reaction product associated with their axolemmae. 4 These results are discussed in relation to the controversial hypothesis of a 'cholinergic link' in noradrenergic transmission."} {"id": "PMID:169933", "title": "The effects of cyclic N-2-O-dibutyryl- adenosine 3',5'-monophosphate, adrenaline and aminophylline on the isometric contractility of the isolated hemidiaphragm of the rat.", "content": "1 N-2-O-dibutyryl adenosine 3',5'-monophosphate (db cyclic AMP), adrenaline and aminophylline produce a potentiation of the tension developed (Td) and the maximum rate of rise of tension (dT/dt max) in the rat isolated diaphragm during indirect electrical stimulation. Aminophylline and db cyclic AMP also produce the same effect during direct stimulation. 2 Propranolol produced a depression of the action of adrenaline on Td and dT/dt max during indirect stimulation of the diaphragm. On the other hand, the potentiating actions of db cyclic AMP and of aminophylline on Td and dT/dt max during indirect stimulation were unaffected by propranolol. 3 The results support the idea that cyclic AMP may be involved not only in regulating the processes associated with synthesis, mobilization and storage of transmitter in the motor nerve terminal, but also in modifying some metabolic processes which regulate the function of the contractile elements.", "contents": "The effects of cyclic N-2-O-dibutyryl- adenosine 3',5'-monophosphate, adrenaline and aminophylline on the isometric contractility of the isolated hemidiaphragm of the rat. 1 N-2-O-dibutyryl adenosine 3',5'-monophosphate (db cyclic AMP), adrenaline and aminophylline produce a potentiation of the tension developed (Td) and the maximum rate of rise of tension (dT/dt max) in the rat isolated diaphragm during indirect electrical stimulation. Aminophylline and db cyclic AMP also produce the same effect during direct stimulation. 2 Propranolol produced a depression of the action of adrenaline on Td and dT/dt max during indirect stimulation of the diaphragm. On the other hand, the potentiating actions of db cyclic AMP and of aminophylline on Td and dT/dt max during indirect stimulation were unaffected by propranolol. 3 The results support the idea that cyclic AMP may be involved not only in regulating the processes associated with synthesis, mobilization and storage of transmitter in the motor nerve terminal, but also in modifying some metabolic processes which regulate the function of the contractile elements."} {"id": "PMID:169934", "title": "Some characteristics of pre- and post-synaptic inhibitory receptors at the hermit crab neuromuscular junction.", "content": "1 The effects of gamma-aminobutyric acid (GABA), beta-guanidinopropionic acid (betaGP) and picrotoxin on the pre- and post-synaptic receptors of the hermit crab neuromuscular junction were studied quantitatively usine electrophysiological techniques. Reductions in excitatory junction potential (e.j.p.) amplitude and membrane resistance were measured simultaneously from the same cells. 2 The pre- and post-synaptic receptors were activated by the same order of concentration of GABA, whereas betaGP stimulated the pre-synaptic receptors at a concentration ten times lower than was required to affect the post-synaptic membrane. 3 Picrotoxin appeared to antagonize the pre-synaptic action of betaGP in a competitive manner. The affinity constants (+/- s.e. mean) for picrotoxin 5 times 10(-6)M and 2 times 10(-4)M were 6.80(+/-0.46) times 10(5)M-1 and 6.42(+/-1.8) times 10(5)M-1 respectively. 4 The effect of GABA on e.j.p. amplitude also appeared to be antagonized competitively by picrotoxin whereas the post-synaptic effect was antagonized in a non-competitive manner. 5 Possible differences in the nature of the pre- and post-synaptic receptors are discussed.", "contents": "Some characteristics of pre- and post-synaptic inhibitory receptors at the hermit crab neuromuscular junction. 1 The effects of gamma-aminobutyric acid (GABA), beta-guanidinopropionic acid (betaGP) and picrotoxin on the pre- and post-synaptic receptors of the hermit crab neuromuscular junction were studied quantitatively usine electrophysiological techniques. Reductions in excitatory junction potential (e.j.p.) amplitude and membrane resistance were measured simultaneously from the same cells. 2 The pre- and post-synaptic receptors were activated by the same order of concentration of GABA, whereas betaGP stimulated the pre-synaptic receptors at a concentration ten times lower than was required to affect the post-synaptic membrane. 3 Picrotoxin appeared to antagonize the pre-synaptic action of betaGP in a competitive manner. The affinity constants (+/- s.e. mean) for picrotoxin 5 times 10(-6)M and 2 times 10(-4)M were 6.80(+/-0.46) times 10(5)M-1 and 6.42(+/-1.8) times 10(5)M-1 respectively. 4 The effect of GABA on e.j.p. amplitude also appeared to be antagonized competitively by picrotoxin whereas the post-synaptic effect was antagonized in a non-competitive manner. 5 Possible differences in the nature of the pre- and post-synaptic receptors are discussed."} {"id": "PMID:169935", "title": "Extraction from ox retractor penis of an inhibitory substance which mimics its atropine-resistant neurogenic relaxation.", "content": "The inhibitory post-ganglionic transmission in the retractor penis of the ox resembles that of the dog and is not cholinergic or adrenergic. Acid extracts of this tissue have yielded an unidentified, labile, inhibitory substance which mimics the effect of its inhibitory nerves.", "contents": "Extraction from ox retractor penis of an inhibitory substance which mimics its atropine-resistant neurogenic relaxation. The inhibitory post-ganglionic transmission in the retractor penis of the ox resembles that of the dog and is not cholinergic or adrenergic. Acid extracts of this tissue have yielded an unidentified, labile, inhibitory substance which mimics the effect of its inhibitory nerves."} {"id": "PMID:169936", "title": "The effects of hypercholesterolaemic plasma on vascular sensitivity to noradrenaline.", "content": "1. The pressor responses to injected noradrenaline (NA) of 42 isolated perfused femoral arteries of the rabbit were studied. 2. Potentiation of the responses was found when hypercholesterolaemic plasma was perfused through the arteries. No change was found with normal plasma. 3. Potentiation of the responses was found when isolated beta-lipoprotein in Krebs solution was perfused. No change was found with similar amounts of bovine-albumen. 4. Pure cholesterol dissolved directly into normal plasma, and dissolved via propanol into Krebs solution or plasma caused no potentiation. Propanol alone in Krebs or plasma had no effect. 5. Potentiation was caused by a decreased equilibrium coefficient (Keq) for the NA-adrenoceptor interaction and an increased maximal pressor response (Rmax). 6. It is concluded that cholesterol carried on its apoprotein is capable of potentiating the pressor effects of noradrenaline.", "contents": "The effects of hypercholesterolaemic plasma on vascular sensitivity to noradrenaline. 1. The pressor responses to injected noradrenaline (NA) of 42 isolated perfused femoral arteries of the rabbit were studied. 2. Potentiation of the responses was found when hypercholesterolaemic plasma was perfused through the arteries. No change was found with normal plasma. 3. Potentiation of the responses was found when isolated beta-lipoprotein in Krebs solution was perfused. No change was found with similar amounts of bovine-albumen. 4. Pure cholesterol dissolved directly into normal plasma, and dissolved via propanol into Krebs solution or plasma caused no potentiation. Propanol alone in Krebs or plasma had no effect. 5. Potentiation was caused by a decreased equilibrium coefficient (Keq) for the NA-adrenoceptor interaction and an increased maximal pressor response (Rmax). 6. It is concluded that cholesterol carried on its apoprotein is capable of potentiating the pressor effects of noradrenaline."} {"id": "PMID:169937", "title": "Dopamine-induced amylase secretion from guinea-pig submandibular gland.", "content": "1. The effects of dopamine, 5-hydroxydopamine (5-OHDA) and noradrenaline on amylase secretion from the guinea-pig submandibular gland were investigated under in vitro conditions. 2. All three amines greatly enhanced amylase secretion. Blockade of dopamine beta-hydroxylase did not inhibit the response to dopamine. 3. Noradrenaline and dopamine stimulated amylase release from salivary glands of reserpine-treated animals, whereas 5-OHDA had no stimulatory effect on secretion in guinea-pigs pretreated with reserpine. 4. Haloperidol completely inhibited dopamine-induced enzyme discharge, but did not affect noradrenaline-initiated secretion. 5. Apomorphine caused a slight enzyme release by itself; it diminished the dopamine secretory effect, but did not modify that of noradrenaline. 6. Pimozide and fluspirilene attenuated the dopamine-induced enzyme discharge, but compared with haloperidol they were less effective. 7. It is concluded that dopamine exerts a secretagogic action different from that of noradrenaline. The possible presence of a specific dopamine receptor in salivary glands is discussed.", "contents": "Dopamine-induced amylase secretion from guinea-pig submandibular gland. 1. The effects of dopamine, 5-hydroxydopamine (5-OHDA) and noradrenaline on amylase secretion from the guinea-pig submandibular gland were investigated under in vitro conditions. 2. All three amines greatly enhanced amylase secretion. Blockade of dopamine beta-hydroxylase did not inhibit the response to dopamine. 3. Noradrenaline and dopamine stimulated amylase release from salivary glands of reserpine-treated animals, whereas 5-OHDA had no stimulatory effect on secretion in guinea-pigs pretreated with reserpine. 4. Haloperidol completely inhibited dopamine-induced enzyme discharge, but did not affect noradrenaline-initiated secretion. 5. Apomorphine caused a slight enzyme release by itself; it diminished the dopamine secretory effect, but did not modify that of noradrenaline. 6. Pimozide and fluspirilene attenuated the dopamine-induced enzyme discharge, but compared with haloperidol they were less effective. 7. It is concluded that dopamine exerts a secretagogic action different from that of noradrenaline. The possible presence of a specific dopamine receptor in salivary glands is discussed."} {"id": "PMID:169938", "title": "Fatal Clostridium welchii septicaemia following acute cholecystitis.", "content": "A case of Clostridium welchii septicaemia following acute cholecystitis is described. The onset was acute and a rapidly fatal outcome ensued. Radiological findings were negative. An approach to the antibiotic treatment and general management is discussed.", "contents": "Fatal Clostridium welchii septicaemia following acute cholecystitis. A case of Clostridium welchii septicaemia following acute cholecystitis is described. The onset was acute and a rapidly fatal outcome ensued. Radiological findings were negative. An approach to the antibiotic treatment and general management is discussed."} {"id": "PMID:169939", "title": "Value of infarct-specific isotope (99mTc-labelled stannous pyrophosphate) in myocardial scanning.", "content": "With the use of 99mTc-labelled stannous pyrophosphate scans positive for myocardial infarction were obtained from 28 patients in the acute stage of the disease. In some cases the scan was positive when the initial electrocardiogram gave equivocal results. Negative scans were obtained from a control group of patients and from eight patients in hospital with chest pain but with no other evidence of recent myocardial infarction.", "contents": "Value of infarct-specific isotope (99mTc-labelled stannous pyrophosphate) in myocardial scanning. With the use of 99mTc-labelled stannous pyrophosphate scans positive for myocardial infarction were obtained from 28 patients in the acute stage of the disease. In some cases the scan was positive when the initial electrocardiogram gave equivocal results. Negative scans were obtained from a control group of patients and from eight patients in hospital with chest pain but with no other evidence of recent myocardial infarction."} {"id": "PMID:169942", "title": "Arsine toxicity aboard the Asiafreighter.", "content": "Eight sailors on board the Asiafreighter were exposed to arsine that had escaped from a cylinder in the cargo hold. Four suffered severe toxicity and within a few hours had developed fever, weakness, nausea, vomiting, diarrhoea, abdominal pain, and haemoglobinuria. These patients had pronounced intravascular haemolysis, which in one patient was complete. This patient was also stuporose and anoxic, a condition attributed to failure of oxygen transport and sludging of red cell debris in the cerebral and pulmonary circulations, but he regained a normal level of consciousness after exchange transfusion. Evidence of marrow depression was present: the reticulocyte response to the haemolysis was poor and there was a thrombocytopenia. All four patients developed renal failure, one being totally anuric for five weeks. Two patients developed peripheral neuropathy, and one was still severely disabled six months after the incident. The other four patients had a similar, though less severe, illness.", "contents": "Arsine toxicity aboard the Asiafreighter. Eight sailors on board the Asiafreighter were exposed to arsine that had escaped from a cylinder in the cargo hold. Four suffered severe toxicity and within a few hours had developed fever, weakness, nausea, vomiting, diarrhoea, abdominal pain, and haemoglobinuria. These patients had pronounced intravascular haemolysis, which in one patient was complete. This patient was also stuporose and anoxic, a condition attributed to failure of oxygen transport and sludging of red cell debris in the cerebral and pulmonary circulations, but he regained a normal level of consciousness after exchange transfusion. Evidence of marrow depression was present: the reticulocyte response to the haemolysis was poor and there was a thrombocytopenia. All four patients developed renal failure, one being totally anuric for five weeks. Two patients developed peripheral neuropathy, and one was still severely disabled six months after the incident. The other four patients had a similar, though less severe, illness."} {"id": "PMID:169950", "title": "Treatment of wounds from animals suspected of carrying neurotropic viruses.", "content": "The methods used at the Clinical Research Centre, Northwick Park Hospital, to treat wounds potentially infected with neurotropic viruses are outlined. Emphasis is laid on first aid and on surgical attention. Patients should remain under medical supervision for at least four weeks after the injury, the need for specific post-exposure treatment depending on the nature of the exposure.", "contents": "Treatment of wounds from animals suspected of carrying neurotropic viruses. The methods used at the Clinical Research Centre, Northwick Park Hospital, to treat wounds potentially infected with neurotropic viruses are outlined. Emphasis is laid on first aid and on surgical attention. Patients should remain under medical supervision for at least four weeks after the injury, the need for specific post-exposure treatment depending on the nature of the exposure."} {"id": "PMID:169951", "title": "Test for left-right chemospecificity in frog cutaneous nerves.", "content": "Studies of the effects of competitive reinnervation by left and right cutaneous nerves were carried out in Rana pipiens in an effort to test for the existence of left-right biochemical differentiation of neural tissue. The dorsal cutaneous nerves were cut, transposed and allowed to regenerate under different conditions of denervation and competition and the resultant reinnervation and reflex patterns were determined by behavioral and electrophysiological mapping techniques. Contrary to earlier findings, there was no indication in the present investigation that the growth patterns were influenced by the laterality of the fibers. Other factors such as availability of terminal sites created by complete or partial denervation and the tendency of fibers to seek terminal connections seemed to override any qualifications imposed by the existence of lateral specificity on the formation of terminal contacts.", "contents": "Test for left-right chemospecificity in frog cutaneous nerves. Studies of the effects of competitive reinnervation by left and right cutaneous nerves were carried out in Rana pipiens in an effort to test for the existence of left-right biochemical differentiation of neural tissue. The dorsal cutaneous nerves were cut, transposed and allowed to regenerate under different conditions of denervation and competition and the resultant reinnervation and reflex patterns were determined by behavioral and electrophysiological mapping techniques. Contrary to earlier findings, there was no indication in the present investigation that the growth patterns were influenced by the laterality of the fibers. Other factors such as availability of terminal sites created by complete or partial denervation and the tendency of fibers to seek terminal connections seemed to override any qualifications imposed by the existence of lateral specificity on the formation of terminal contacts."} {"id": "PMID:169953", "title": "Endogenous phosphorylation of four cerebral cortical membrane proteins: role of cyclic nucleotides, ATP and divalent cations.", "content": "Endogenous phosphorylation of 4 membrane-bound protein components of cerebral cortex was studied in vitro. Cyclic AMP was shown to stimulate phosphorylation to a major extent in protein components designated D, E and G, but to a minor extent in protein component F. The time course of phosphorylation of each of these components is affected differently by (a) the presence of cyclic nucleotides or zinc ions and (b) the concentration of ATP and magnesium ions in the reaction mixture. Although a different membrane preparation was used here than by Ueda et al., molecular weight determination and response to divalent cations, magnesium and zinc, suggest that components D and E may be the same as their proteins I and II. The newly described phosphoproteins, F and G, are respectively the least and most stimulated by the addition of cyclic AMP. Under certain conditions phosphate content in protein E can be increased by cyclic AMP and decreased by cyclic GMP.23Author", "contents": "Endogenous phosphorylation of four cerebral cortical membrane proteins: role of cyclic nucleotides, ATP and divalent cations. Endogenous phosphorylation of 4 membrane-bound protein components of cerebral cortex was studied in vitro. Cyclic AMP was shown to stimulate phosphorylation to a major extent in protein components designated D, E and G, but to a minor extent in protein component F. The time course of phosphorylation of each of these components is affected differently by (a) the presence of cyclic nucleotides or zinc ions and (b) the concentration of ATP and magnesium ions in the reaction mixture. Although a different membrane preparation was used here than by Ueda et al., molecular weight determination and response to divalent cations, magnesium and zinc, suggest that components D and E may be the same as their proteins I and II. The newly described phosphoproteins, F and G, are respectively the least and most stimulated by the addition of cyclic AMP. Under certain conditions phosphate content in protein E can be increased by cyclic AMP and decreased by cyclic GMP.23Author"} {"id": "PMID:169955", "title": "Thyrotropin releasing hormone (TRH): apparent receptor binding in rat brain membranes.", "content": "Thyrotropin releasing hormone (TRH) binds to membranes of rat brain tissue via high- and low-affinity binding components. The high-affinity binding of TRH to brain membranes resembles binding to pituitary membranes in terms of its affinity and specificity for most peptides. In equilibrium studies, the affinity and specificity for most peptides. In equilibrium studies, the dissociation constant for high-affinity binding to brain membranes is about 50 dissociation constant for high-affinity binding to brain membranes is about 50nM, which is about the same as for aat pituitary membranes, while low-affinity binding to brain membranes has a dissociation constant of about 5 muM. Liver membranes display low-affinity binding for TRH with a dissociation constant similar to the low-affinity binding component of brain membranes. No high-affinity binding can be detected with liver membranes. Negligible saturable binding to TRH can be detected with membranes of any tissues examined other than liver, pituitary and brain...", "contents": "Thyrotropin releasing hormone (TRH): apparent receptor binding in rat brain membranes. Thyrotropin releasing hormone (TRH) binds to membranes of rat brain tissue via high- and low-affinity binding components. The high-affinity binding of TRH to brain membranes resembles binding to pituitary membranes in terms of its affinity and specificity for most peptides. In equilibrium studies, the affinity and specificity for most peptides. In equilibrium studies, the dissociation constant for high-affinity binding to brain membranes is about 50 dissociation constant for high-affinity binding to brain membranes is about 50nM, which is about the same as for aat pituitary membranes, while low-affinity binding to brain membranes has a dissociation constant of about 5 muM. Liver membranes display low-affinity binding for TRH with a dissociation constant similar to the low-affinity binding component of brain membranes. No high-affinity binding can be detected with liver membranes. Negligible saturable binding to TRH can be detected with membranes of any tissues examined other than liver, pituitary and brain..."} {"id": "PMID:169966", "title": "Metabolic responses of the awake cerebral cortex to anoxia hypoxia spreading depression and epileptiform activity.", "content": "Using the time sharing fluorometer/reflectometer the measurement of NADH fluorescence as well as the reflected light was obtained from the surface of the awake rat brain cortex. The light was transferred to and from the brain via a flexible light pipe (made of quartz fibers) connected to a cannula implanted permanently above the brain. Exposing the rat to pure nitrogen atmosphere increased the fluorescence (reduction of NADH) by 32.3 +/- 6.1% in comparison to the normoxic fluorescence level. During cortical spreading depression (SD) the NADH fluorescence decreased (oxidation of NADH) by 17.3 +/- 2.8%. Exposing the rat to nitrogen after SD was elicited blocked the oxidation cycle observed during SD. Exposing the awake ras to 10, 7.5 or 5% O2 did not block the response of the brain to spreading depression or to Metrazol applied locally to the cortex. Under hypoxic conditions the brain showed a typical response to SD, namely, an oxidation cycle of NADH except that the duration of the cycle was longer and the decrease in the NADH level was smaller. The EEG activity recovered to normal even under 5%. The same effect of hypoxia was found when Metrazol was applied and epileptic activity was developed.", "contents": "Metabolic responses of the awake cerebral cortex to anoxia hypoxia spreading depression and epileptiform activity. Using the time sharing fluorometer/reflectometer the measurement of NADH fluorescence as well as the reflected light was obtained from the surface of the awake rat brain cortex. The light was transferred to and from the brain via a flexible light pipe (made of quartz fibers) connected to a cannula implanted permanently above the brain. Exposing the rat to pure nitrogen atmosphere increased the fluorescence (reduction of NADH) by 32.3 +/- 6.1% in comparison to the normoxic fluorescence level. During cortical spreading depression (SD) the NADH fluorescence decreased (oxidation of NADH) by 17.3 +/- 2.8%. Exposing the rat to nitrogen after SD was elicited blocked the oxidation cycle observed during SD. Exposing the awake ras to 10, 7.5 or 5% O2 did not block the response of the brain to spreading depression or to Metrazol applied locally to the cortex. Under hypoxic conditions the brain showed a typical response to SD, namely, an oxidation cycle of NADH except that the duration of the cycle was longer and the decrease in the NADH level was smaller. The EEG activity recovered to normal even under 5%. The same effect of hypoxia was found when Metrazol was applied and epileptic activity was developed."} {"id": "PMID:169967", "title": "Recruitment and firing rate modulation of motor unit tension in a small muscle of the cat's foot.", "content": "Maintained contractions were elicited in the first deep lumbrical muscle of the cat's foot by electrical stimulation of the contralateral motor cortex or, reflexly, by pinching of the foot pad. The discharges of all significant motor units of the muscle were monitored by electromyography, and contractions of the various motor units were observed in isometric recordings of muscle tension. Over a wide range, muscle tension could be enhanced by an increased intensity of pad pinching or cortical stimulation. This increase in muscle tension was caused by a recruitment of new motor units as well as by an increase in the firing rate of already active motor units. The latter mechanism was clearly of great importance. Pad pinching or cortical stimulation could sometimes cause the muscle to produce a tension close to that of a maximum tetanic contraction. This was several times greater than the mean tension that would have been caused by motor unit recruitment alone (i.e. by the motor units firing at their minimum steady rate). Cortical stimulation as well as pad pinching commonly recruited weak units more easily than stronger ones of the same muscle. The recruitment order obtained in response to pad pinching often differed, however, in various details from the recruitment caused by cortical stimulation.", "contents": "Recruitment and firing rate modulation of motor unit tension in a small muscle of the cat's foot. Maintained contractions were elicited in the first deep lumbrical muscle of the cat's foot by electrical stimulation of the contralateral motor cortex or, reflexly, by pinching of the foot pad. The discharges of all significant motor units of the muscle were monitored by electromyography, and contractions of the various motor units were observed in isometric recordings of muscle tension. Over a wide range, muscle tension could be enhanced by an increased intensity of pad pinching or cortical stimulation. This increase in muscle tension was caused by a recruitment of new motor units as well as by an increase in the firing rate of already active motor units. The latter mechanism was clearly of great importance. Pad pinching or cortical stimulation could sometimes cause the muscle to produce a tension close to that of a maximum tetanic contraction. This was several times greater than the mean tension that would have been caused by motor unit recruitment alone (i.e. by the motor units firing at their minimum steady rate). Cortical stimulation as well as pad pinching commonly recruited weak units more easily than stronger ones of the same muscle. The recruitment order obtained in response to pad pinching often differed, however, in various details from the recruitment caused by cortical stimulation."} {"id": "PMID:169968", "title": "Evaluation of inactivated infectious bovine rhinotracheitis vaccines.", "content": "Sixty-five calves of approximately three months of age and of mixed sex were vaccinated twice at four week intervals with either attenuated or inactivated infectious bovine rhinotracheitis vaccines. Following initial vaccination there was no demonstrable serum infectious bovine rhinotracheitis titer in any of the calves receiving the inactivated vaccine with 20.7% of the calves receiving the attenuated vaccines having demonstrable titers. Following a second administration of vaccine at eight weeks post-initial vaccination 63.9% of the calves receiving the inactivated vaccine had no demonstrable titer with 72.4% of the calves receiving the attenuated vaccine exhibiting a blood titer of four or greater.", "contents": "Evaluation of inactivated infectious bovine rhinotracheitis vaccines. Sixty-five calves of approximately three months of age and of mixed sex were vaccinated twice at four week intervals with either attenuated or inactivated infectious bovine rhinotracheitis vaccines. Following initial vaccination there was no demonstrable serum infectious bovine rhinotracheitis titer in any of the calves receiving the inactivated vaccine with 20.7% of the calves receiving the attenuated vaccines having demonstrable titers. Following a second administration of vaccine at eight weeks post-initial vaccination 63.9% of the calves receiving the inactivated vaccine had no demonstrable titer with 72.4% of the calves receiving the attenuated vaccine exhibiting a blood titer of four or greater."} {"id": "PMID:169969", "title": "Identification of multiple equine infectious anemia antigens by immunodiffusion reactions.", "content": "Equine infectious anemia (EIA) cell antigens prepared from infected equine spleen, equine leukocyte cultures or a persistently infected equine dermis cell line contained at least two serologically reacting components. For convenience one component was designated as soluble antigen (SA) and the other as cell-associated antigen (CAA). The SA appeared as a single component when it was prepared from EIA virus precipitated from infectious tissue culture fluid with polyethylene glycol and ether treated but it was mixed with CAA when the source was infected cells. Cytolytic or mechanical disruption of infected cells appeared to accelerate the release of CAA. Reaction to each component could be identified in double and radial immunodiffusion tests by increasing the concentrations of SA in a two-component antigenic mixture. The CAA component does not appear to affect the value of the immunodiffusion test as a diagnostic aid.", "contents": "Identification of multiple equine infectious anemia antigens by immunodiffusion reactions. Equine infectious anemia (EIA) cell antigens prepared from infected equine spleen, equine leukocyte cultures or a persistently infected equine dermis cell line contained at least two serologically reacting components. For convenience one component was designated as soluble antigen (SA) and the other as cell-associated antigen (CAA). The SA appeared as a single component when it was prepared from EIA virus precipitated from infectious tissue culture fluid with polyethylene glycol and ether treated but it was mixed with CAA when the source was infected cells. Cytolytic or mechanical disruption of infected cells appeared to accelerate the release of CAA. Reaction to each component could be identified in double and radial immunodiffusion tests by increasing the concentrations of SA in a two-component antigenic mixture. The CAA component does not appear to affect the value of the immunodiffusion test as a diagnostic aid."} {"id": "PMID:169970", "title": "In vitro antimicrobial sensitivity of Mycoplasmas isolated from the bovine genital tract.", "content": "The in vitro antimicrobial sensitivity of 14 mycoplasma and 13 ureaplasma strains isolated from the genital tracts of bulls was examined. It was found that at relatively low concentrations, tetracycline, declomycin and tylosin were lethal to both types of organisms. Lincospectin, berenil, streptomycin and erythromycin were lethal to mycoplasmas but were only inhibitory to the ureaplasma strains at the same concentrations. Polymyxin B and novobiocin were ineffective at the levels tested.", "contents": "In vitro antimicrobial sensitivity of Mycoplasmas isolated from the bovine genital tract. The in vitro antimicrobial sensitivity of 14 mycoplasma and 13 ureaplasma strains isolated from the genital tracts of bulls was examined. It was found that at relatively low concentrations, tetracycline, declomycin and tylosin were lethal to both types of organisms. Lincospectin, berenil, streptomycin and erythromycin were lethal to mycoplasmas but were only inhibitory to the ureaplasma strains at the same concentrations. Polymyxin B and novobiocin were ineffective at the levels tested."} {"id": "PMID:169971", "title": "Viral susceptibility of a cell line derived from the pig oviduct.", "content": "Seventeen of 24 RNA viruses and eight of nine DNA viruses replicated in a cell line derived from a pig fallopian tube. The following RNA viruses grew poorly in it: the virus of transmissible gastroenteritis of pig and the swine-influenza, Sendai and bovine para-influenza type 3 viruses. Among other RNA viruses an untyped swine para-myxovirus and some picornaviruses, rhabdoviruses and togaviruses attained high titers and produced an extensive cytopathic effect. Among the DNA viruses a porcine adeno, equine rhinopneumonitis, infectious bovine rhinotraceheitis, pseudorabies and porcine cytomegalo viruses replicated in pig fallopian tube cells as well as in other cells generally used to grow them.", "contents": "Viral susceptibility of a cell line derived from the pig oviduct. Seventeen of 24 RNA viruses and eight of nine DNA viruses replicated in a cell line derived from a pig fallopian tube. The following RNA viruses grew poorly in it: the virus of transmissible gastroenteritis of pig and the swine-influenza, Sendai and bovine para-influenza type 3 viruses. Among other RNA viruses an untyped swine para-myxovirus and some picornaviruses, rhabdoviruses and togaviruses attained high titers and produced an extensive cytopathic effect. Among the DNA viruses a porcine adeno, equine rhinopneumonitis, infectious bovine rhinotraceheitis, pseudorabies and porcine cytomegalo viruses replicated in pig fallopian tube cells as well as in other cells generally used to grow them."} {"id": "PMID:169972", "title": "Transmissible gastroenteritis (TGE) of swine: effect of age of swine testes cells culture monolayers on plaque assays of TGE virus.", "content": "A continuous line of swine testes cell culture monolayers was infected at various ages with both cell culture-adapted transmissible gastroenteritis (TGE) virus and tissue infected with TGE virus. Both produced increasing numbers of plaques as the cell monolayers aged from two to five days. Therefore, allowing the swine testes cell monolayer to age five to six days before inoculation should increase the likelihood of detecting TGE virus by plaque assay.", "contents": "Transmissible gastroenteritis (TGE) of swine: effect of age of swine testes cells culture monolayers on plaque assays of TGE virus. A continuous line of swine testes cell culture monolayers was infected at various ages with both cell culture-adapted transmissible gastroenteritis (TGE) virus and tissue infected with TGE virus. Both produced increasing numbers of plaques as the cell monolayers aged from two to five days. Therefore, allowing the swine testes cell monolayer to age five to six days before inoculation should increase the likelihood of detecting TGE virus by plaque assay."} {"id": "PMID:169973", "title": "An outbreak of avian encephalomyelitis in turkeys in Canada.", "content": "An outbreak of avian encephalomyelitis in two week old turkey poults is described. The disease was diagnosed by the fluorescent antibody technique and was confirmed by neutralization tests conducted in chicks.", "contents": "An outbreak of avian encephalomyelitis in turkeys in Canada. An outbreak of avian encephalomyelitis in two week old turkey poults is described. The disease was diagnosed by the fluorescent antibody technique and was confirmed by neutralization tests conducted in chicks."} {"id": "PMID:169974", "title": "An adrenal cell system suitable for long term study of factors affecting steroidogenesis.", "content": "Cell suspensions of normal adult rad adrenals have been prepared by trypsinization and incubated in Ham's nutrient mixture F10 containing horse serum, fetal calf serum, and lima bean trypsin inhibitor. In most experiments culture medium was not changed during incubation. In this system the number of cells fell to 50% after 2 days, then slowly declined to 20% after 1 month of incubation. A corticosterone (B) response was seen to as little as 5 muU of ACTH per millilitre, a concentration which is within the range found in normal rat serum. With maximal stimulation (100 mU ACTH/ml) the rate of accumulation was highest during the first 24 h then slowly decreased over the following 9 days. When in separate experiments ACTH was added after various times of incubation up to 3 weeks, there was a B response which continued for as long as 1 week after the ACTH was added; the later the time at which ACTH was added the lesser was the initial B response and the longer the lag period before a substantial response occurred. In cell suspensions in medium containing 5.0 mequiv. of K+ per litre, aldosterone content increased for approximately 24 h, then showed little or no change over the next 9 days. With increased K+ concentration, aldosterone was found in greater amounts and accumulation continued for longer periods, both without and with ACTH. This adrenal cell system appears suitable for long term study of factors affecting steroidogenesis.", "contents": "An adrenal cell system suitable for long term study of factors affecting steroidogenesis. Cell suspensions of normal adult rad adrenals have been prepared by trypsinization and incubated in Ham's nutrient mixture F10 containing horse serum, fetal calf serum, and lima bean trypsin inhibitor. In most experiments culture medium was not changed during incubation. In this system the number of cells fell to 50% after 2 days, then slowly declined to 20% after 1 month of incubation. A corticosterone (B) response was seen to as little as 5 muU of ACTH per millilitre, a concentration which is within the range found in normal rat serum. With maximal stimulation (100 mU ACTH/ml) the rate of accumulation was highest during the first 24 h then slowly decreased over the following 9 days. When in separate experiments ACTH was added after various times of incubation up to 3 weeks, there was a B response which continued for as long as 1 week after the ACTH was added; the later the time at which ACTH was added the lesser was the initial B response and the longer the lag period before a substantial response occurred. In cell suspensions in medium containing 5.0 mequiv. of K+ per litre, aldosterone content increased for approximately 24 h, then showed little or no change over the next 9 days. With increased K+ concentration, aldosterone was found in greater amounts and accumulation continued for longer periods, both without and with ACTH. This adrenal cell system appears suitable for long term study of factors affecting steroidogenesis."} {"id": "PMID:169975", "title": "Adrenocorticotropin secretion rates following histamine injection in adult and newborn dogs.", "content": "The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1-7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 mug/kg, while the last dose was 62-108 mug/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1-7 days each received one injection of histamine of 76-116 mug/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion.", "contents": "Adrenocorticotropin secretion rates following histamine injection in adult and newborn dogs. The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1-7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 mug/kg, while the last dose was 62-108 mug/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1-7 days each received one injection of histamine of 76-116 mug/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion."} {"id": "PMID:169976", "title": "Uncoupling of lipolysis from cyclic AMP by procaine: a tool for studying the mechanism of action of antilipolytic agents.", "content": "The initial rate of net glycerol release in norepinephrine-stimulated adipose tissue fragments was inhibited (40-78%) by procaine-HCl (1-5mM), whereas basal (unstimulated) lipolysis was unaffected. A dose-related inhibition of norepinephrine-induced lipolysis by procaine-HCl (0.1-1 mM) also occurred in adipocytes. Procaine-induced antilipolysis was associated with an augmented rather than a reduced hormone-stimulated increment in intracellular cyclic AMP. The dissociation of lipolysis from cyclic AMP accumulation has been termed the uncoupling effect of procaine. This effect of procaine was employed to define the precise mechanism of action of the antilipolytic drug clofibrate (Atromid-S) which inhibits lipolysis by reducing cyclic AMP. A reduction in cyclic AMP by clofibrate was demonstrated in norepinephrine-stimulated cells exposed to procaine (uncoupled system). Thus, the inhibitory effect of clofibrate on cyclic AMP could not be attributed to accumulation of products of lipolysis. Because neither procaine-HCl nor clofibrate had any effect on the low Km 3':5'-cyclic-AMP phosphodiesterase (EC 3.1.4.17) activity in hormone stimulated cells, the clofibrate-induced reduction in cyclic AMP was attributed to its direct action on adipocyte adenylate cyclase.", "contents": "Uncoupling of lipolysis from cyclic AMP by procaine: a tool for studying the mechanism of action of antilipolytic agents. The initial rate of net glycerol release in norepinephrine-stimulated adipose tissue fragments was inhibited (40-78%) by procaine-HCl (1-5mM), whereas basal (unstimulated) lipolysis was unaffected. A dose-related inhibition of norepinephrine-induced lipolysis by procaine-HCl (0.1-1 mM) also occurred in adipocytes. Procaine-induced antilipolysis was associated with an augmented rather than a reduced hormone-stimulated increment in intracellular cyclic AMP. The dissociation of lipolysis from cyclic AMP accumulation has been termed the uncoupling effect of procaine. This effect of procaine was employed to define the precise mechanism of action of the antilipolytic drug clofibrate (Atromid-S) which inhibits lipolysis by reducing cyclic AMP. A reduction in cyclic AMP by clofibrate was demonstrated in norepinephrine-stimulated cells exposed to procaine (uncoupled system). Thus, the inhibitory effect of clofibrate on cyclic AMP could not be attributed to accumulation of products of lipolysis. Because neither procaine-HCl nor clofibrate had any effect on the low Km 3':5'-cyclic-AMP phosphodiesterase (EC 3.1.4.17) activity in hormone stimulated cells, the clofibrate-induced reduction in cyclic AMP was attributed to its direct action on adipocyte adenylate cyclase."} {"id": "PMID:169977", "title": "[Nitrosoguanidine-induced attenuated Clostridium perfringens type A mutant in gas gangrene].", "content": "A fully virulent classical type A strain of Clostridium perfringens was treated during its logarithmic growth phase with 100 mug/ml of N-m\u00e9thyl-N'-nitro-N-nitrosoguanidine, the bacteria being exposed to the mutagen for 30 min at 37 degrees C in a phosphate buffer adjusted to pH 6.2; after treatment the suspension was streaked on sheep blood agar plates, and colonies that showed an alteration in the theta-hemolysis pattern were selected for isolation. The virulence of two mutants, thus altered in their theta-hemolysis, was studied. One, designated LNG 5, was still capable of killing most of the inoculated guinea pigs in less than 24 h with all the clinical, macroscopic, and bacteriological signs of gas gangrene; however, histological sections showed that tissue damage was not as marked as with the wild strain. On the contrary, the second mutant, labelled LNG 11, was completely avirulent as far as gas gangrene was concerned; indeed, the injection of fluid cultures containing 1 times 10(8) - 10(9)/ml viable bacteria, was not followed by any clinical, bacteriological, or histological signs of gas gangrene. However, strain LNG 11 did give rise to a firm swelling of the inoculated thigh with a corresponding acute inflammatory response of the connective tissue, although the muscle fiber was unaltered. Eventually, this local reaction was followed by necrosis of the skin accompanied by an acute or subacute inflammation with fibroblastic proliferation. These superficial lesions healed spontaneously. They could not be reproduced with crude filtrate alone or with washed bacilli. Strain LNG 11 was therefore considered to be soletly an attenuated strain since, although avirulent as far as gas gangrene is concerned. it is still capable of producing low levels of toxic material. This appears to be the first time that such a strain of C. perfringens type A has been obtained by nitrosoguanidine treatment.", "contents": "[Nitrosoguanidine-induced attenuated Clostridium perfringens type A mutant in gas gangrene]. A fully virulent classical type A strain of Clostridium perfringens was treated during its logarithmic growth phase with 100 mug/ml of N-m\u00e9thyl-N'-nitro-N-nitrosoguanidine, the bacteria being exposed to the mutagen for 30 min at 37 degrees C in a phosphate buffer adjusted to pH 6.2; after treatment the suspension was streaked on sheep blood agar plates, and colonies that showed an alteration in the theta-hemolysis pattern were selected for isolation. The virulence of two mutants, thus altered in their theta-hemolysis, was studied. One, designated LNG 5, was still capable of killing most of the inoculated guinea pigs in less than 24 h with all the clinical, macroscopic, and bacteriological signs of gas gangrene; however, histological sections showed that tissue damage was not as marked as with the wild strain. On the contrary, the second mutant, labelled LNG 11, was completely avirulent as far as gas gangrene was concerned; indeed, the injection of fluid cultures containing 1 times 10(8) - 10(9)/ml viable bacteria, was not followed by any clinical, bacteriological, or histological signs of gas gangrene. However, strain LNG 11 did give rise to a firm swelling of the inoculated thigh with a corresponding acute inflammatory response of the connective tissue, although the muscle fiber was unaltered. Eventually, this local reaction was followed by necrosis of the skin accompanied by an acute or subacute inflammation with fibroblastic proliferation. These superficial lesions healed spontaneously. They could not be reproduced with crude filtrate alone or with washed bacilli. Strain LNG 11 was therefore considered to be soletly an attenuated strain since, although avirulent as far as gas gangrene is concerned. it is still capable of producing low levels of toxic material. This appears to be the first time that such a strain of C. perfringens type A has been obtained by nitrosoguanidine treatment."} {"id": "PMID:169978", "title": "Supersensitivity of central neurons--a brief review of an emerging concept.", "content": "The concept that \"denervation\" or \"pharmacological disuse\" supersensitivity develops in central neuronal systems subsequent to sustained attenuation of normal neurohumoral mechanisms is reviewed. Particular emphasis is placed on biochemical and electrophysiological parameters of supersensitivity in dopaminergic (striatal) neuronal systems. The possible applicability of theories invoking changes in receptor sensitivity to the phenomenon of narcotic tolerance and physical dependence and to psychoactive drug therapy is discussed.", "contents": "Supersensitivity of central neurons--a brief review of an emerging concept. The concept that \"denervation\" or \"pharmacological disuse\" supersensitivity develops in central neuronal systems subsequent to sustained attenuation of normal neurohumoral mechanisms is reviewed. Particular emphasis is placed on biochemical and electrophysiological parameters of supersensitivity in dopaminergic (striatal) neuronal systems. The possible applicability of theories invoking changes in receptor sensitivity to the phenomenon of narcotic tolerance and physical dependence and to psychoactive drug therapy is discussed."} {"id": "PMID:169979", "title": "Pituitary melanocorticotrophinoma with amyloid deposition.", "content": "The light and electron microscopic features of a pituitary adenoma composed of adrenocorticotrophic hormone (ACTH) and melanocyte stimulating hormone (MSH) cells with perivascular amyloid deposition is reported. Histochemical and fine structural data indicate that this material is APUDamyloid and is present in the extra-cellular perivascular spaces. It is suggested that the differences in fine structure and of distribution of the amyloid in pituitary adenomas is dependent upon the cell of origin.", "contents": "Pituitary melanocorticotrophinoma with amyloid deposition. The light and electron microscopic features of a pituitary adenoma composed of adrenocorticotrophic hormone (ACTH) and melanocyte stimulating hormone (MSH) cells with perivascular amyloid deposition is reported. Histochemical and fine structural data indicate that this material is APUDamyloid and is present in the extra-cellular perivascular spaces. It is suggested that the differences in fine structure and of distribution of the amyloid in pituitary adenomas is dependent upon the cell of origin."} {"id": "PMID:169980", "title": "Why transcortical reflexes?", "content": "Experiments in humans and in monkeys have indicated that load perturbations, occurring during voluntary movements and postural activity, may be automatically compensated for. Overall muscle stiffness opposing load changes is determined by the visco-elastic properties of the muscle, by segmental reflex actions and finally by long-loop reflexes. Under certain circumstances, for instance when the subject or the experimental monkey is \"prepared\" to counteract perturbations which are unpredictable in time, the long-loop \"reflexes\" appear to be responsible for most of the corrective muscle tension. Experiments in anaesthetized monkeys revealed that signals from stretch afferents reach neurons of the motor cortex, possibly via a relay in the cortical area 3a. The latencies of these responses to well controlled muscle stretches were in the same range as motor cortical cell discharges recorded in alert monkeys subjected to load perturbations. Furthermore, these responses of cells in the motor cortex also had the appropriate timing to indicate a causal relationship with the long-latency electromyographic responses to load changes referred to above. These experimental results therefore strongly support the hypothesis, first proposed by Phillips (1969), of a transcortical servo-loop adjusting motor cortical output according to the load conditions in which movements are performed. The major advantage of transcortical regulations as opposed to segmental regulations, seems to be a powerful gain control acting at the cortical level; it was repeatedly shown that the long-loop reflexes are strongly modifiable and under voluntary control. It is suggested that an adaptive gain control at the cortical level is a prerequisite to preserve the complex capabilities of the motor cortex as the chief \"executive\" for skilled, preprogrammed movements. A loss of this adaptive gain control may be, at least partly, the cause of motor disorders such as rigidity in Parkinsonian patients, as reported by Tatton and Lee (1975). It is suggested that further investigations of the control of transcortical reflexes may aid in the understanding of the pathophysiology of motor disabilities.", "contents": "Why transcortical reflexes? Experiments in humans and in monkeys have indicated that load perturbations, occurring during voluntary movements and postural activity, may be automatically compensated for. Overall muscle stiffness opposing load changes is determined by the visco-elastic properties of the muscle, by segmental reflex actions and finally by long-loop reflexes. Under certain circumstances, for instance when the subject or the experimental monkey is \"prepared\" to counteract perturbations which are unpredictable in time, the long-loop \"reflexes\" appear to be responsible for most of the corrective muscle tension. Experiments in anaesthetized monkeys revealed that signals from stretch afferents reach neurons of the motor cortex, possibly via a relay in the cortical area 3a. The latencies of these responses to well controlled muscle stretches were in the same range as motor cortical cell discharges recorded in alert monkeys subjected to load perturbations. Furthermore, these responses of cells in the motor cortex also had the appropriate timing to indicate a causal relationship with the long-latency electromyographic responses to load changes referred to above. These experimental results therefore strongly support the hypothesis, first proposed by Phillips (1969), of a transcortical servo-loop adjusting motor cortical output according to the load conditions in which movements are performed. The major advantage of transcortical regulations as opposed to segmental regulations, seems to be a powerful gain control acting at the cortical level; it was repeatedly shown that the long-loop reflexes are strongly modifiable and under voluntary control. It is suggested that an adaptive gain control at the cortical level is a prerequisite to preserve the complex capabilities of the motor cortex as the chief \"executive\" for skilled, preprogrammed movements. A loss of this adaptive gain control may be, at least partly, the cause of motor disorders such as rigidity in Parkinsonian patients, as reported by Tatton and Lee (1975). It is suggested that further investigations of the control of transcortical reflexes may aid in the understanding of the pathophysiology of motor disabilities."} {"id": "PMID:169982", "title": "Prognosis and treatment of Wilms' tumor at Great Ormond Street Hospital for Sick Children--1960-1972.", "content": "Eighty-one children with a diagnosis of Wilms' tumor who were treated at the Great Ormond Street Hospital for Sick Children between 1960 and 1972 are reviewed. The National Wilms' Tumor Study group staging system is used. Distribution by age and sex in each stage together with survival rate is given. Treatment and prognostic factors are discussed. Wilms' tumor is most common in children below the age of 3 years. There was a survival rate of 87% in Stage I, 36% in Stage II, 8% in Stage III, and 33% in Stage IV. The survival was worse in patients with locally advanced tumor than in patients who had pulmonary metastases in association with a locally resectable tumor. Whole abdominal irradiation is necessary in all patients in whom the tumor has breached the renal capsule. Single agent chemotherapy has not proved effective in preventing relapse in patients with advanced tumors. More intensive therapy is needed in this group to prevent both local recurrence and distant metastases. The addition of multiple drug chemotherapy to nephrectomy and whole abdominal irradiation is already improving the disease-free survival.", "contents": "Prognosis and treatment of Wilms' tumor at Great Ormond Street Hospital for Sick Children--1960-1972. Eighty-one children with a diagnosis of Wilms' tumor who were treated at the Great Ormond Street Hospital for Sick Children between 1960 and 1972 are reviewed. The National Wilms' Tumor Study group staging system is used. Distribution by age and sex in each stage together with survival rate is given. Treatment and prognostic factors are discussed. Wilms' tumor is most common in children below the age of 3 years. There was a survival rate of 87% in Stage I, 36% in Stage II, 8% in Stage III, and 33% in Stage IV. The survival was worse in patients with locally advanced tumor than in patients who had pulmonary metastases in association with a locally resectable tumor. Whole abdominal irradiation is necessary in all patients in whom the tumor has breached the renal capsule. Single agent chemotherapy has not proved effective in preventing relapse in patients with advanced tumors. More intensive therapy is needed in this group to prevent both local recurrence and distant metastases. The addition of multiple drug chemotherapy to nephrectomy and whole abdominal irradiation is already improving the disease-free survival."} {"id": "PMID:169983", "title": "Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication.", "content": "In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks. All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively. The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively. The median survival of the evaluable patients is 8 months (range 1-13 months). The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia. Adriamycin seems to be an effective agent in hepatocellular carcinoma. Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor.", "contents": "Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication. In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks. All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively. The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively. The median survival of the evaluable patients is 8 months (range 1-13 months). The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia. Adriamycin seems to be an effective agent in hepatocellular carcinoma. Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor."} {"id": "PMID:169984", "title": "Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).", "content": "The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy.", "contents": "Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441). The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy."} {"id": "PMID:169985", "title": "Ectopic placental proteins in nontrophoblastic tumors. Serial measurements following chemotherapy.", "content": "Four men with metastatic carcinoma (two bronchus, one stomach, one primary unknown) and ectopic placental protein production (one chorionic gonadotropin (hCG and its alpha subunit; one placental lactogen (hPL); one hCG alone; one hCG and hPL) were studied with serial retrospective measurements of the ectopic protein concentrations in serum, correlated with objective assessment of clinical status. The biochemical marker and clinical response were documented during treatment with a variety of agents and during periods without therapy. Of nine assessable periods, seven showed concordance of biochemical marker and clinical responses.", "contents": "Ectopic placental proteins in nontrophoblastic tumors. Serial measurements following chemotherapy. Four men with metastatic carcinoma (two bronchus, one stomach, one primary unknown) and ectopic placental protein production (one chorionic gonadotropin (hCG and its alpha subunit; one placental lactogen (hPL); one hCG alone; one hCG and hPL) were studied with serial retrospective measurements of the ectopic protein concentrations in serum, correlated with objective assessment of clinical status. The biochemical marker and clinical response were documented during treatment with a variety of agents and during periods without therapy. Of nine assessable periods, seven showed concordance of biochemical marker and clinical responses."} {"id": "PMID:169986", "title": "Herpes simplex encephalitis in Hodgkins disease. Isolation of drug-sensitive virus from brain following unsuccessful treatment with idoxuridine.", "content": "Herpes simplex encephalitis developed in a patient with Hodgkin's disease under therapy. Despite treatment with idoxuridine in a total dose of 280 mg/kg intravenously, he died without showing any clinical response. At autopsy, there was no gross or microscopic evidence of Hodgkin's disease, and virus isolated from the brain postmortem was inhibited in vitro by idoxuridine 0.5 mug/ml. Failure of idoxuridine to affect the course of infection by a drug-sensitive virus may be due to poor tissue penetration, although the role of the Hodgkin's disease cannot be discounted.", "contents": "Herpes simplex encephalitis in Hodgkins disease. Isolation of drug-sensitive virus from brain following unsuccessful treatment with idoxuridine. Herpes simplex encephalitis developed in a patient with Hodgkin's disease under therapy. Despite treatment with idoxuridine in a total dose of 280 mg/kg intravenously, he died without showing any clinical response. At autopsy, there was no gross or microscopic evidence of Hodgkin's disease, and virus isolated from the brain postmortem was inhibited in vitro by idoxuridine 0.5 mug/ml. Failure of idoxuridine to affect the course of infection by a drug-sensitive virus may be due to poor tissue penetration, although the role of the Hodgkin's disease cannot be discounted."} {"id": "PMID:169987", "title": "Ultrastructure of human bronchiolo-alveolar cell carcinoma.", "content": "Ultrastructural features were correlated with a series of special staining reactions in eight cases of bronchiolo-alveolar carcinoma. Ultrastructural, all tumors were similarly composed of large cells with abundant cytoplasm and small nuclei in close contact with each other. Straight membranes or complex interdigitations occurred within adjacent tumor cells, attached to each other by scattered desmosomes. Microvilli or cilia abutted from free surfaces of the cells, and were noted in different stages of evolution. Numerous organelles were seen in the cytoplasm, including prominent mitochondria and single or coalescent secretory vacuoles with granular matrix resembling mucin. Other cytosomes less commonly found were irregular, partially lamellated inclusions and dark, homogeneous structures without limiting membranes. The stroma of the tumors was rich in elastin and collagen. Both the number of secretory vacuoles in the cytoplasm of tumor cells and the amount of connective tissue fibrils in the stroma of the tumors correlated well with the findings in the series of special staining reactions. No definite ultrastructural feature was present to identify the tumors as orginating from Type II alveolar epithelial cells, but the possibility exists that they arose in the bronchiole, from undifferentiated basal cells or mucinous cells per se. Our impression in these eight cases studied is consistent with the view that bronchiolo-alveolar carcinomas are indistinguishable at the ultrastructural level from other bronchogenic adenocarcinomas.", "contents": "Ultrastructure of human bronchiolo-alveolar cell carcinoma. Ultrastructural features were correlated with a series of special staining reactions in eight cases of bronchiolo-alveolar carcinoma. Ultrastructural, all tumors were similarly composed of large cells with abundant cytoplasm and small nuclei in close contact with each other. Straight membranes or complex interdigitations occurred within adjacent tumor cells, attached to each other by scattered desmosomes. Microvilli or cilia abutted from free surfaces of the cells, and were noted in different stages of evolution. Numerous organelles were seen in the cytoplasm, including prominent mitochondria and single or coalescent secretory vacuoles with granular matrix resembling mucin. Other cytosomes less commonly found were irregular, partially lamellated inclusions and dark, homogeneous structures without limiting membranes. The stroma of the tumors was rich in elastin and collagen. Both the number of secretory vacuoles in the cytoplasm of tumor cells and the amount of connective tissue fibrils in the stroma of the tumors correlated well with the findings in the series of special staining reactions. No definite ultrastructural feature was present to identify the tumors as orginating from Type II alveolar epithelial cells, but the possibility exists that they arose in the bronchiole, from undifferentiated basal cells or mucinous cells per se. Our impression in these eight cases studied is consistent with the view that bronchiolo-alveolar carcinomas are indistinguishable at the ultrastructural level from other bronchogenic adenocarcinomas."} {"id": "PMID:169988", "title": "An ultrastructural study of mixed hepatoblastoma with osteoid elements.", "content": "A case of mixed hepatoblastoma with osteoid elements was studied by light and electron microscopy. The ultrastructure of the epithelial elements showed a lack of differentiation and simple cytoplasmic organelles. However, an occasional cytoplasmic crystalloid structure were seen. The ultrastructure of the osteoid foci showed fibroblast-like cells capable of collagen formation, clearly distinguishable from the epithelial elements. These cells had neoplastic characteristics of nuclear pleomorphism and high nucleo-cytoplasmic ratio. These findings support the belief that hepatoblastoma arises from a multipotential blastema capable of both epithelial and mesenchymal differentiation, with the osteoid elements being an intrinsic neoplastic component of the tumor.", "contents": "An ultrastructural study of mixed hepatoblastoma with osteoid elements. A case of mixed hepatoblastoma with osteoid elements was studied by light and electron microscopy. The ultrastructure of the epithelial elements showed a lack of differentiation and simple cytoplasmic organelles. However, an occasional cytoplasmic crystalloid structure were seen. The ultrastructure of the osteoid foci showed fibroblast-like cells capable of collagen formation, clearly distinguishable from the epithelial elements. These cells had neoplastic characteristics of nuclear pleomorphism and high nucleo-cytoplasmic ratio. These findings support the belief that hepatoblastoma arises from a multipotential blastema capable of both epithelial and mesenchymal differentiation, with the osteoid elements being an intrinsic neoplastic component of the tumor."} {"id": "PMID:169989", "title": "Primary liver cancer coincident with Schistosomiasis japonica. A study of 24 necropsies.", "content": "The etiologic relationship of parasitic liver disease to primary liver cancer has long been debated. For this reason, a review of 4611 necropsies was carried out to determine the frequency with which hepatocellular carcinoma occurred in association with schistosomiasis. Of 227 cases of hepatocellular carcinoma, 24 (10.6%) were associated with schistosomiasis japonica. This was significantly higher than the incidence of this carcinoma without schistosomiasis (2.78%). The majority of the 24 cases exhibited the features of a mixed macronodular and micronodular cirrhosis (Gall's posthepatitic cirrhosis); this was super-imposed upon and caused a masking of schistosomiasis fibrosis. By radioimmunoassay hepatitis B antigen was positive in 27% of these cases. A review of the literature indicated that chronic schistosomiasis, on its own, is unlikely to be the cause of primary liver cell carcinoma. Histologic features resembling post-hepatitic cirrhosis combined with a high frequency of hepatitis B antigen suggest that viral hepatitis rather than S. japonicum is the more likely etiologic factor involved, or has a synergistic effect on carcinogenesis.", "contents": "Primary liver cancer coincident with Schistosomiasis japonica. A study of 24 necropsies. The etiologic relationship of parasitic liver disease to primary liver cancer has long been debated. For this reason, a review of 4611 necropsies was carried out to determine the frequency with which hepatocellular carcinoma occurred in association with schistosomiasis. Of 227 cases of hepatocellular carcinoma, 24 (10.6%) were associated with schistosomiasis japonica. This was significantly higher than the incidence of this carcinoma without schistosomiasis (2.78%). The majority of the 24 cases exhibited the features of a mixed macronodular and micronodular cirrhosis (Gall's posthepatitic cirrhosis); this was super-imposed upon and caused a masking of schistosomiasis fibrosis. By radioimmunoassay hepatitis B antigen was positive in 27% of these cases. A review of the literature indicated that chronic schistosomiasis, on its own, is unlikely to be the cause of primary liver cell carcinoma. Histologic features resembling post-hepatitic cirrhosis combined with a high frequency of hepatitis B antigen suggest that viral hepatitis rather than S. japonicum is the more likely etiologic factor involved, or has a synergistic effect on carcinogenesis."} {"id": "PMID:169992", "title": "Radioautographic study of the rat brain and pituitary after injection of 3H dexamethasone.", "content": "The central nervous system and the pituitary of adrenalectomized male rats injected with 3H-dexamethasone were examined by radioautography. At 1 hr after the injection, radioactivity concentration was high in the medial basal hypothalamus, the pituitary and the pineal gland. In the hypothalamus, radioactive material was found to be selectively concentrated in neurons in the ventral part of nucleus arcuatus and in the infundibular region. In the anterior pituitary, a large proportion of cells showed silver grains both in the cytoplasm and over the cell nuclei. However, in a small number of cells, the radioactive material was associated with the cell nuclei. Less radioactivity was present in the intermediate and posterior lobes. The pineal gland contained more silver grains than did other regions of the brain. The results obtained in the present study suggest essentially an action of dexamethasone in the medial basal hypothalamus and at the level of the pituitary.", "contents": "Radioautographic study of the rat brain and pituitary after injection of 3H dexamethasone. The central nervous system and the pituitary of adrenalectomized male rats injected with 3H-dexamethasone were examined by radioautography. At 1 hr after the injection, radioactivity concentration was high in the medial basal hypothalamus, the pituitary and the pineal gland. In the hypothalamus, radioactive material was found to be selectively concentrated in neurons in the ventral part of nucleus arcuatus and in the infundibular region. In the anterior pituitary, a large proportion of cells showed silver grains both in the cytoplasm and over the cell nuclei. However, in a small number of cells, the radioactive material was associated with the cell nuclei. Less radioactivity was present in the intermediate and posterior lobes. The pineal gland contained more silver grains than did other regions of the brain. The results obtained in the present study suggest essentially an action of dexamethasone in the medial basal hypothalamus and at the level of the pituitary."} {"id": "PMID:169993", "title": "Inhibitor induced alterations of chromatoid bodies in male germ line cells of Xenopus laevis.", "content": "The action of inhibitors of protein synthesis on the structure of cytoplasmic inclusions found in the male germ cell line of the anuran, Xenopus laevis, has been studied by light and electron microscopy. Results indicate that one such inclusion, the chromatoid body, is sensitive to treatment with either chloramphenicol or puromycin. These drugs administered in vivo or in vitro cause up to a thirty-fold increase in the volume of the chromatoid body in all stages where it is normally present. Maximum size increase obtainable is the same for either drug, but is different and characteristic for each germ cell stage. Drug action is dose dependent, with \"chromatoid body syndrome\" occurring over a relatively narrow concentration range. Cyclohexamide, in contrast to chloramphenicol or puromycin, does not produce a clear increase in the size of chromatoid bodies, and is capable of blocking the action of the other drugs at normally effective concentrations. Results obtained in this investigation suggest that primary spermatogonia contain enough chromatoid body material to account for the total amount present in all subsequent germ cell stages. This fact, coupled with other studies where chromatoid-like bodies have been observed, suggests the hypothesis that the chromatoid body represents at least in part an aggregation stage of materials associated with the microtubule population of the germ cell line. Alternately, or in addition, ribonucleoprotein may contribute to the structure of the chromatoid body.", "contents": "Inhibitor induced alterations of chromatoid bodies in male germ line cells of Xenopus laevis. The action of inhibitors of protein synthesis on the structure of cytoplasmic inclusions found in the male germ cell line of the anuran, Xenopus laevis, has been studied by light and electron microscopy. Results indicate that one such inclusion, the chromatoid body, is sensitive to treatment with either chloramphenicol or puromycin. These drugs administered in vivo or in vitro cause up to a thirty-fold increase in the volume of the chromatoid body in all stages where it is normally present. Maximum size increase obtainable is the same for either drug, but is different and characteristic for each germ cell stage. Drug action is dose dependent, with \"chromatoid body syndrome\" occurring over a relatively narrow concentration range. Cyclohexamide, in contrast to chloramphenicol or puromycin, does not produce a clear increase in the size of chromatoid bodies, and is capable of blocking the action of the other drugs at normally effective concentrations. Results obtained in this investigation suggest that primary spermatogonia contain enough chromatoid body material to account for the total amount present in all subsequent germ cell stages. This fact, coupled with other studies where chromatoid-like bodies have been observed, suggests the hypothesis that the chromatoid body represents at least in part an aggregation stage of materials associated with the microtubule population of the germ cell line. Alternately, or in addition, ribonucleoprotein may contribute to the structure of the chromatoid body."} {"id": "PMID:169994", "title": "Ultrastructure of the adenohypophysis in the teleost Poecilia latipinna.", "content": "In the sailfin molly, Poecilia latipinna, seven morphological endocrine cell-types could be distinguished with the electron microscope. Each of these was identified with one of the seven cell-types distinguished with the light microscope, to most of which endocrine functions have previously been allocated. Corticotrophs and prolactin cells form the rostral pars distalis, and the proximal pars distalis consists of an outer layer of gonadotrophs and an inner zone containing growth hormone cells and thyrotrophs. The pars intermedia contains two cell-types, of uncertain function. Stellate cells (interstitial cells) occur throughout the adenohypophysis, but are most numerous and prominent in the rostral pars distalis. The inner proximal pars distalis contains a cell-type not previously distinguished in this species with the light microscope, the Z-cell, which could be aminergic. The ultrastructural features of each cell-type are described in detail, and discussed in comparisons with the homologous cells described in other teleosts. There is good agreement for different teleosts in the ultrastructural details of each cell type.", "contents": "Ultrastructure of the adenohypophysis in the teleost Poecilia latipinna. In the sailfin molly, Poecilia latipinna, seven morphological endocrine cell-types could be distinguished with the electron microscope. Each of these was identified with one of the seven cell-types distinguished with the light microscope, to most of which endocrine functions have previously been allocated. Corticotrophs and prolactin cells form the rostral pars distalis, and the proximal pars distalis consists of an outer layer of gonadotrophs and an inner zone containing growth hormone cells and thyrotrophs. The pars intermedia contains two cell-types, of uncertain function. Stellate cells (interstitial cells) occur throughout the adenohypophysis, but are most numerous and prominent in the rostral pars distalis. The inner proximal pars distalis contains a cell-type not previously distinguished in this species with the light microscope, the Z-cell, which could be aminergic. The ultrastructural features of each cell-type are described in detail, and discussed in comparisons with the homologous cells described in other teleosts. There is good agreement for different teleosts in the ultrastructural details of each cell type."} {"id": "PMID:169995", "title": "Corticoid uptake by the paraventricular nucleus in the hypothalamus of the duck, Anas platyrhynchos.", "content": "3H-corticoids were localized by autoradiography in small neurons in the area of the magnocellular paraventricular nucleus of mallard ducks. Correlative data show that: (1) the label is principally unmetabolized steroid, (2) the hypothalamus competitively binds corticosterone, (3) the paraventricular nucleus contains immunoreactive neurophysin, is richly innervated by boutons of monoaminergic nerves and is involved in the adaptive response to osmotic stress.", "contents": "Corticoid uptake by the paraventricular nucleus in the hypothalamus of the duck, Anas platyrhynchos. 3H-corticoids were localized by autoradiography in small neurons in the area of the magnocellular paraventricular nucleus of mallard ducks. Correlative data show that: (1) the label is principally unmetabolized steroid, (2) the hypothalamus competitively binds corticosterone, (3) the paraventricular nucleus contains immunoreactive neurophysin, is richly innervated by boutons of monoaminergic nerves and is involved in the adaptive response to osmotic stress."} {"id": "PMID:169990", "title": "Disposition of cytosine arabinoside (NSC-63878) and its metabolites: a pharmacokinetic simulation.", "content": "A computer-based model of the pharmacokinetics of cytosine arabinoside (ara-C) and its active metabolite, ara-CTP, has been developed. This model, which is an intracellular extension of the Bischoff-Dedrick model of multi-organ pharmcokinetics gives predictions which are in agreement with the recent measurements of Chou et al on tissue concentrations of ara-CTP and Borsa et al on blood levels of ara-C. It is shown that the ara-CTP halving time in tissue is much greater than the ara-C halving time in blood because of low tissue levels of phosphatase. For a single dose at the LD10 level in mice, significant splenic DNA inhibition is calculated to occur for 26 hours, while the ara-C levels are negligible in 6 hours. The calculated duration of cytostatic effect at lower dosages (2.5 mg/kg) is 10 or 12 hours, while ara-C blood levels are negligible within 3 hours. Implications for cell kinetics and scheduling studies are also briefly described.", "contents": "Disposition of cytosine arabinoside (NSC-63878) and its metabolites: a pharmacokinetic simulation. A computer-based model of the pharmacokinetics of cytosine arabinoside (ara-C) and its active metabolite, ara-CTP, has been developed. This model, which is an intracellular extension of the Bischoff-Dedrick model of multi-organ pharmcokinetics gives predictions which are in agreement with the recent measurements of Chou et al on tissue concentrations of ara-CTP and Borsa et al on blood levels of ara-C. It is shown that the ara-CTP halving time in tissue is much greater than the ara-C halving time in blood because of low tissue levels of phosphatase. For a single dose at the LD10 level in mice, significant splenic DNA inhibition is calculated to occur for 26 hours, while the ara-C levels are negligible in 6 hours. The calculated duration of cytostatic effect at lower dosages (2.5 mg/kg) is 10 or 12 hours, while ara-C blood levels are negligible within 3 hours. Implications for cell kinetics and scheduling studies are also briefly described."} {"id": "PMID:169996", "title": "Ontogenesis of the alpha-MSH, beta-MSH and ACTH cells in the foetal hypophysis of the rat. Correlation with the growth of the adrenals and adrenocortical activity.", "content": "Pituitary sections from 15 to 21 day-old rat foetuses have been studied with the immunofluorescence technique, using antibodies anti alpha-MSH, anti beta-MSH and anti beta (1-24) ACTH. The first ACTH cells appear on day 17 of pregnancy in the pars distalis of the hypophysis and only on day 18 in the pars intermedia. beta-msh cells have been observed on day 16 in the pars anterior and on day 17 in the pars intermedia, while alpha-MSH cells appear only on day 18 and exclusively in the pars intermedia. The cytodifferentiation of the beta-MSH and ACTH cells occurs in the pars intermedia with about a 24 hours delay in comparison to that of the pars distalis. The first revealed cells are always located in the posterior half of the pituitary gland. The corticostimulating activity of the hypophysis has been tested with the fluorescence intensity of the corticotrophs, the adrenal weight, the adrenal content in corticosterone and the plasma corticosterone level. The fluorescence of the corticotrophs increases on day 18, shows a maximum on day 19 and decreases until term. The adrenal weight rises regularly between day 16 to day 20, thereafer the increase subsides. Adrenal and plasma corticosterone concentrations reach a peak on day 19 of pregnancy. These data suggest that hypophyseal corticostimulating activity is very high between days 18 and 19 and decreases between days 19 and 21.", "contents": "Ontogenesis of the alpha-MSH, beta-MSH and ACTH cells in the foetal hypophysis of the rat. Correlation with the growth of the adrenals and adrenocortical activity. Pituitary sections from 15 to 21 day-old rat foetuses have been studied with the immunofluorescence technique, using antibodies anti alpha-MSH, anti beta-MSH and anti beta (1-24) ACTH. The first ACTH cells appear on day 17 of pregnancy in the pars distalis of the hypophysis and only on day 18 in the pars intermedia. beta-msh cells have been observed on day 16 in the pars anterior and on day 17 in the pars intermedia, while alpha-MSH cells appear only on day 18 and exclusively in the pars intermedia. The cytodifferentiation of the beta-MSH and ACTH cells occurs in the pars intermedia with about a 24 hours delay in comparison to that of the pars distalis. The first revealed cells are always located in the posterior half of the pituitary gland. The corticostimulating activity of the hypophysis has been tested with the fluorescence intensity of the corticotrophs, the adrenal weight, the adrenal content in corticosterone and the plasma corticosterone level. The fluorescence of the corticotrophs increases on day 18, shows a maximum on day 19 and decreases until term. The adrenal weight rises regularly between day 16 to day 20, thereafer the increase subsides. Adrenal and plasma corticosterone concentrations reach a peak on day 19 of pregnancy. These data suggest that hypophyseal corticostimulating activity is very high between days 18 and 19 and decreases between days 19 and 21."} {"id": "PMID:169997", "title": "Trophic influences of sympathetic nerves and cyclic AMP on differentiation and proliferation of isolated smooth muscle cells in culture.", "content": "Smooth muscle cells of the newborn guinea-pig vas deferens dispersed into single cells and grown in culture maintain their differentiation for approximately 5 days before undergoing dedifferentiation and mitosis. The presence of sympathetic nerve fibres in contact with the isolated cells delays this process by 3-7 days (Chamley et al., 1974). A similar delay in dedifferentiation of vas deferens smooth muscle cells in tissue culture in the presence of sympathetic ganglion extract is described in the present report, demonstrating that the trophic effect is elicited by a chemical substance. This effect is mimicked by the presence of either a confluent layer of RKA epithelial cells, dibutyryl cyclic AMP or theophylline. A similar, but considerably weaker, effect is also obtained with spinal cord and liver extracts and noradrenaline. Acetylcholine does not show an effect. It is suggested that a trophic substance (probably not noradrenaline) from sympathetic neurons activates the adenyl cyclase system of smooth muscle cells to increase the intracellular level of cyclic AMP which in turn promotes and maintains the differentiation of the cultured smooth muscle cells.", "contents": "Trophic influences of sympathetic nerves and cyclic AMP on differentiation and proliferation of isolated smooth muscle cells in culture. Smooth muscle cells of the newborn guinea-pig vas deferens dispersed into single cells and grown in culture maintain their differentiation for approximately 5 days before undergoing dedifferentiation and mitosis. The presence of sympathetic nerve fibres in contact with the isolated cells delays this process by 3-7 days (Chamley et al., 1974). A similar delay in dedifferentiation of vas deferens smooth muscle cells in tissue culture in the presence of sympathetic ganglion extract is described in the present report, demonstrating that the trophic effect is elicited by a chemical substance. This effect is mimicked by the presence of either a confluent layer of RKA epithelial cells, dibutyryl cyclic AMP or theophylline. A similar, but considerably weaker, effect is also obtained with spinal cord and liver extracts and noradrenaline. Acetylcholine does not show an effect. It is suggested that a trophic substance (probably not noradrenaline) from sympathetic neurons activates the adenyl cyclase system of smooth muscle cells to increase the intracellular level of cyclic AMP which in turn promotes and maintains the differentiation of the cultured smooth muscle cells."} {"id": "PMID:169998", "title": "The retinal pigment epithelium and photoreceptor cells. Light- and electron microscopic studies on monkey eyes.", "content": "In the perifoveal retina of the monkey, Cercopithecus aethiops, the melanin granules are accumulated in apical cytoplasmatic protrusions of the pigment epithelial cells, facing the end of the cones. The rods are inserted deeper into the pigment epithelium than the cones; they reach the bottom of the infoldings of the apical surface membrane of the pigment epithelial cells. No melanin granules or other inclusions are situated at the end of the rods. The outer extremity of the rods is considerably inclined and in sections often appears as groups of rod discs which are incompletely or completely separated from the main part of the outer segments. This separation is regarded as an artifact caused by the inclination of the rods, and it is therefore not considered to represent phagocytosis of the outer segments by the pigment epithelium. The inclusions of the pigment epithelial cells are classified in five categories which seem to be related to each other owing to their shared structural characteristics. It is suggested that melanin granules are produced, modified and destroyed by the pigment epithelial cells of the adult. Because of the relations between the photoreceptors and the melanin granules it is suggested that light scattered by the melanin granules may pass backwards through the outer segments of the cones, but not of the rods.", "contents": "The retinal pigment epithelium and photoreceptor cells. Light- and electron microscopic studies on monkey eyes. In the perifoveal retina of the monkey, Cercopithecus aethiops, the melanin granules are accumulated in apical cytoplasmatic protrusions of the pigment epithelial cells, facing the end of the cones. The rods are inserted deeper into the pigment epithelium than the cones; they reach the bottom of the infoldings of the apical surface membrane of the pigment epithelial cells. No melanin granules or other inclusions are situated at the end of the rods. The outer extremity of the rods is considerably inclined and in sections often appears as groups of rod discs which are incompletely or completely separated from the main part of the outer segments. This separation is regarded as an artifact caused by the inclination of the rods, and it is therefore not considered to represent phagocytosis of the outer segments by the pigment epithelium. The inclusions of the pigment epithelial cells are classified in five categories which seem to be related to each other owing to their shared structural characteristics. It is suggested that melanin granules are produced, modified and destroyed by the pigment epithelial cells of the adult. Because of the relations between the photoreceptors and the melanin granules it is suggested that light scattered by the melanin granules may pass backwards through the outer segments of the cones, but not of the rods."} {"id": "PMID:169999", "title": "Ultrastructural identification of umbilical cord vein endothelium in situ and in culture.", "content": "The ultrastructure of human umbilical cord vein endothelium in situ, after isolation by collagenase treatment, and in primary culture is described. The cultured cells formed a monolayer with typical \"butt\" and interdigitated junctions with specialized areas, and contained Weibel-Palade bodies, rod-shaped tubular organelles considered specific of endothelial cells. These morphological features were not present in cultures of human skin fibroblasts and fibroblast-like cells derived from umbilical cords. It is thus concluded that endothelial cells retain their characteristic fine structure in primary culture. Simple ultrastructural studies can thus be used to identify endothelial cells in culture.", "contents": "Ultrastructural identification of umbilical cord vein endothelium in situ and in culture. The ultrastructure of human umbilical cord vein endothelium in situ, after isolation by collagenase treatment, and in primary culture is described. The cultured cells formed a monolayer with typical \"butt\" and interdigitated junctions with specialized areas, and contained Weibel-Palade bodies, rod-shaped tubular organelles considered specific of endothelial cells. These morphological features were not present in cultures of human skin fibroblasts and fibroblast-like cells derived from umbilical cords. It is thus concluded that endothelial cells retain their characteristic fine structure in primary culture. Simple ultrastructural studies can thus be used to identify endothelial cells in culture."} {"id": "PMID:170000", "title": "Immunofluorescent localization of sites binding anti-synthetic LHRH serum in the median eminence of the greenfinch (Chloris chloris L.).", "content": "With an indirect immunofluorescence technique and an antiserum raised against synthetic LHRH, immunofluorescent granules were observed in fine radially oriented fibres in the palisade layer of the zoma externa in both the anterior and the posterior divisions of the median eminence in the greenfinch. There was no specific immunofluorescence in the tractus supraoptico-hypophyseus. It is concluded that the greenfinch median eminence contains material which is similar to mammalian LHRH.", "contents": "Immunofluorescent localization of sites binding anti-synthetic LHRH serum in the median eminence of the greenfinch (Chloris chloris L.). With an indirect immunofluorescence technique and an antiserum raised against synthetic LHRH, immunofluorescent granules were observed in fine radially oriented fibres in the palisade layer of the zoma externa in both the anterior and the posterior divisions of the median eminence in the greenfinch. There was no specific immunofluorescence in the tractus supraoptico-hypophyseus. It is concluded that the greenfinch median eminence contains material which is similar to mammalian LHRH."} {"id": "PMID:170001", "title": "Studies on the function of polyadenylic acid on poliovirus RNA.", "content": "RNAase H was used to remove selectively over 83% of 3' terminal polyadenylic acid [poly(A)] from poliovirus RNA. In a single cycle infection with this poly(A)-deficient RNA, no evidence for multiplication of the RNA was found. To elucidate further the function of poliovirus poly (A), the translational capacity of the RNAase H-treated and untreated RNA was studied in a cell-free protein synthesizing system prepared from HeLa cells. Removal of most of the poly(A) did not affect the pattern or amount of polypeptides synthesized. We conclude that the poly(A) on poliovirus RNA is probably necessary to the replication of the molecule.", "contents": "Studies on the function of polyadenylic acid on poliovirus RNA. RNAase H was used to remove selectively over 83% of 3' terminal polyadenylic acid [poly(A)] from poliovirus RNA. In a single cycle infection with this poly(A)-deficient RNA, no evidence for multiplication of the RNA was found. To elucidate further the function of poliovirus poly (A), the translational capacity of the RNAase H-treated and untreated RNA was studied in a cell-free protein synthesizing system prepared from HeLa cells. Removal of most of the poly(A) did not affect the pattern or amount of polypeptides synthesized. We conclude that the poly(A) on poliovirus RNA is probably necessary to the replication of the molecule."} {"id": "PMID:170002", "title": "Creatine kinase, myokinase, and acetylcholinesterase activities in muscle-forming primary cultures of mouse teratocarcinoma cells.", "content": "Multipotential mouse teratocarcinoma cells in embryoid bodies were explanted on plastic or collagen substrates. Various modes of cell determination, including myogenesis, occurred. The predominant avenue of differentiation soon became myogenesis: many multinucleated myotubes formed and yielded an extensive network of skeletal muscle fibers. The process does not proceed to normal completion, as the fibers have a paucity of striations and are not contractile. Activities of several enzymes ordinarily associated with muscle differentiation were examined. Acetylcholinesterase activity increases, especially during myotube formation, as in normal myogenesis. However, creatine kinase activity rises during myotube formation and then drops abnormally, and myokinase activity fails to increase appreciably. The fetal isozymic form of creatine kinase is expressed in the cultures, although well differentiated solid tumors taken from mice show attainment of the adult muscle isozyme type if skeletal muscle is demonstrably present. The results are consistent with the interpretation that coordinately regulated changes in gene expressions controlling these functions may be required for later stages of myogenesis.", "contents": "Creatine kinase, myokinase, and acetylcholinesterase activities in muscle-forming primary cultures of mouse teratocarcinoma cells. Multipotential mouse teratocarcinoma cells in embryoid bodies were explanted on plastic or collagen substrates. Various modes of cell determination, including myogenesis, occurred. The predominant avenue of differentiation soon became myogenesis: many multinucleated myotubes formed and yielded an extensive network of skeletal muscle fibers. The process does not proceed to normal completion, as the fibers have a paucity of striations and are not contractile. Activities of several enzymes ordinarily associated with muscle differentiation were examined. Acetylcholinesterase activity increases, especially during myotube formation, as in normal myogenesis. However, creatine kinase activity rises during myotube formation and then drops abnormally, and myokinase activity fails to increase appreciably. The fetal isozymic form of creatine kinase is expressed in the cultures, although well differentiated solid tumors taken from mice show attainment of the adult muscle isozyme type if skeletal muscle is demonstrably present. The results are consistent with the interpretation that coordinately regulated changes in gene expressions controlling these functions may be required for later stages of myogenesis."} {"id": "PMID:170003", "title": "Genetic control of chlorophyll biosynthesis in chlamydomonas: analysis of a mutant affecting synthesis of delta-aminolevulinic acid.", "content": "A Mendelian mutation, r-1, in Chlamydomonas reinhardtii has been isolated which elevates protoporphyrin accumulation of the Mendelian protoporphyrin mutants brS-1 and brC-1 more than 20 fold. This increased protoporphyrin accumulation is shown to result from increased delta-aminolevulinic acid synthesis in the double mutants brS-1 r-1 and brC-1 r-1 over that of brS-1 and brC-1 alone. By itself, the r-1 mutation has no detectable protoporphyrin accumulation and has reduced levels of delta-aminolevulinic acid synthesizing activity, chlorophyll, protoheme, and cytochrome oxidase activity. The low levels of chlorophyll and protoheme in r-1 can be increased by feeding delta-aminolevulinic acid. We hypothesize that r-1 may be a mutation of the gene coding for the delta-aminolevulinic acid synthesizing enzyme which reduces the sensitivity of this enzyme to feedback inhibition by protoporphyrin or heme as well as reducing the overall activity of the enzyme. Evidence is also presented for a single delta-aminolevulinic acid synthesizing enzyme serving both chlorophyll and heme biosynthesis.", "contents": "Genetic control of chlorophyll biosynthesis in chlamydomonas: analysis of a mutant affecting synthesis of delta-aminolevulinic acid. A Mendelian mutation, r-1, in Chlamydomonas reinhardtii has been isolated which elevates protoporphyrin accumulation of the Mendelian protoporphyrin mutants brS-1 and brC-1 more than 20 fold. This increased protoporphyrin accumulation is shown to result from increased delta-aminolevulinic acid synthesis in the double mutants brS-1 r-1 and brC-1 r-1 over that of brS-1 and brC-1 alone. By itself, the r-1 mutation has no detectable protoporphyrin accumulation and has reduced levels of delta-aminolevulinic acid synthesizing activity, chlorophyll, protoheme, and cytochrome oxidase activity. The low levels of chlorophyll and protoheme in r-1 can be increased by feeding delta-aminolevulinic acid. We hypothesize that r-1 may be a mutation of the gene coding for the delta-aminolevulinic acid synthesizing enzyme which reduces the sensitivity of this enzyme to feedback inhibition by protoporphyrin or heme as well as reducing the overall activity of the enzyme. Evidence is also presented for a single delta-aminolevulinic acid synthesizing enzyme serving both chlorophyll and heme biosynthesis."} {"id": "PMID:170009", "title": "[Effects of theophylline on chemically induced liver tumorogenesis and on bladder membranes in rats].", "content": "The addition of theophylline to the diet of rats given the carcinogen 4-dimethylaminoazobenzene did not significantly impair the development of hepatomas. In contrast, the feeding of theophylline has been associated to some histopathological changes in bladder membrane leading to the occurrence of malignant papillomas.", "contents": "[Effects of theophylline on chemically induced liver tumorogenesis and on bladder membranes in rats]. The addition of theophylline to the diet of rats given the carcinogen 4-dimethylaminoazobenzene did not significantly impair the development of hepatomas. In contrast, the feeding of theophylline has been associated to some histopathological changes in bladder membrane leading to the occurrence of malignant papillomas."} {"id": "PMID:170010", "title": "[Interconvertibility of molecular forms of 3'5' cyclic AMP phosphodiesterase of human platelets].", "content": "Three forms of cyclic AMP phosphodiesterase from human platelets are resolved upon sucrose gradient centrifugation : 2.5S (monomer), 4.8S (dimer) and 7S (tetramer). They are interconvertible and form an association-dissociation equilibrium depending on the concentration of enzyme. The dissociated form has a high Km for cyclic AMP (Km : 3-5.10(-4) M) whereas the associated form has a low Km (Km : 3-5.10(-5) M).", "contents": "[Interconvertibility of molecular forms of 3'5' cyclic AMP phosphodiesterase of human platelets]. Three forms of cyclic AMP phosphodiesterase from human platelets are resolved upon sucrose gradient centrifugation : 2.5S (monomer), 4.8S (dimer) and 7S (tetramer). They are interconvertible and form an association-dissociation equilibrium depending on the concentration of enzyme. The dissociated form has a high Km for cyclic AMP (Km : 3-5.10(-4) M) whereas the associated form has a low Km (Km : 3-5.10(-5) M)."} {"id": "PMID:170007", "title": "[Coprologic survey in Bilharzia infected children of the Adzope region (Ivory Coast)].", "content": "During a stool examination survey on 174 bilharzia attained children living in a rural area of Ivory Coast, 93% were found to have intestinal parasites mainly Entamoeba coli, Necator americanus and Ascaris lumbricoides. The prevalence of the cysts of Entamoeba histolytica (4,7%) is lower than the one found in France (7%). Concerning the other intestinal parasites, their respective occurrence have been compared with those noted in other regions of Ivory Coast and of Africa.", "contents": "[Coprologic survey in Bilharzia infected children of the Adzope region (Ivory Coast)]. During a stool examination survey on 174 bilharzia attained children living in a rural area of Ivory Coast, 93% were found to have intestinal parasites mainly Entamoeba coli, Necator americanus and Ascaris lumbricoides. The prevalence of the cysts of Entamoeba histolytica (4,7%) is lower than the one found in France (7%). Concerning the other intestinal parasites, their respective occurrence have been compared with those noted in other regions of Ivory Coast and of Africa."} {"id": "PMID:170013", "title": "[Androgen receptors in the cytosol of normal mucosa and of pharyngo-laryngeal epitheliomas in humans].", "content": "Specific binding for 5 alpha dihydrotestosterone has been characterized in cytosol fraction from human pharyngeal and laryngeal mucosae. The high binding affinity of the protein receptor (Kd 2 x 10(-10)M) and its low capacity are similar in both sexes, and similar in both normal mucosa and epithelioma.", "contents": "[Androgen receptors in the cytosol of normal mucosa and of pharyngo-laryngeal epitheliomas in humans]. Specific binding for 5 alpha dihydrotestosterone has been characterized in cytosol fraction from human pharyngeal and laryngeal mucosae. The high binding affinity of the protein receptor (Kd 2 x 10(-10)M) and its low capacity are similar in both sexes, and similar in both normal mucosa and epithelioma."} {"id": "PMID:170014", "title": "[Pralidoxime prevents certain teratogenic effects induced by bidrin in quail embryos].", "content": "Bidrin treatment of quail embryos results in axial anomalies as well as malformations of the beak and the limbs. Whereas the administration of pralidoxime to teratogen-treated embryos prevents the appearance of the axial anomalies, the morphogenesis of the beak and limbs remains profoundly altered.", "contents": "[Pralidoxime prevents certain teratogenic effects induced by bidrin in quail embryos]. Bidrin treatment of quail embryos results in axial anomalies as well as malformations of the beak and the limbs. Whereas the administration of pralidoxime to teratogen-treated embryos prevents the appearance of the axial anomalies, the morphogenesis of the beak and limbs remains profoundly altered."} {"id": "PMID:170018", "title": "Noninvasive quantitation of myocardial infarction with technetium 99m pyrophosphate.", "content": "We sought to quantitate infarct size using radioactive imaging techniques. Infarcts were created in closed chest dogs. Using a scintillation camera interfaced to a computer, infarct images were made in the anterior, left lateral, LAO, and RAO projections, 48 hours after infarction and 75 to 90 min following the intravenous injection of 15 mCi of Technetium 99m pyrophosphate (Tc-PYP). Images were computer enhanced and area was calibrated with a radioactive grid source of known dimensions. Image radioactivity was normalized for decay and dose corrected for body weight. Animals were sacrificed two hours following the injection Tc-PYP. Postmortem images were also computer enhanced and calibrated. Gross infarct area and weight were estimated and transmural biopsies were evaluated for Tc-PYP activity and analyzed for creatine phosphokinase (CPK) content. Contiguous biopsies were pathologically analyzed and graded. There was a negative correlation between tissue Tc-PYP activity and CPK content (r=0.89). Pathologic severity worsened with increased Tc-PYP activity and diminished CPK content. There was a good correlation between gross infarct area and image infarct area, both in vivo (r", "contents": "Noninvasive quantitation of myocardial infarction with technetium 99m pyrophosphate. We sought to quantitate infarct size using radioactive imaging techniques. Infarcts were created in closed chest dogs. Using a scintillation camera interfaced to a computer, infarct images were made in the anterior, left lateral, LAO, and RAO projections, 48 hours after infarction and 75 to 90 min following the intravenous injection of 15 mCi of Technetium 99m pyrophosphate (Tc-PYP). Images were computer enhanced and area was calibrated with a radioactive grid source of known dimensions. Image radioactivity was normalized for decay and dose corrected for body weight. Animals were sacrificed two hours following the injection Tc-PYP. Postmortem images were also computer enhanced and calibrated. Gross infarct area and weight were estimated and transmural biopsies were evaluated for Tc-PYP activity and analyzed for creatine phosphokinase (CPK) content. Contiguous biopsies were pathologically analyzed and graded. There was a negative correlation between tissue Tc-PYP activity and CPK content (r=0.89). Pathologic severity worsened with increased Tc-PYP activity and diminished CPK content. There was a good correlation between gross infarct area and image infarct area, both in vivo (r"} {"id": "PMID:170019", "title": "Biochemical studies on tissues from a patient with Lafora disease.", "content": "Tissues from the cerebral cortex, liver and myocardium of a patient with Lafora disease were obtained at autopsy and were studied biochemically. 1. Glucose content in the myocardium and liver was almost nil while that in the controls was 0.66 mg/g wet weight in the former and 8.80 mg/g wet weight in the latter. Glycogen content in the cerebral cortex and myocardium was about 10 and 3 times more than in controls. 2. Polyglucosan extracted from the cerebral cortex, liver and myocardium had a longer exterior glucose chain than that in the liver of the control but a normal, alpha or beta 1,4-glucosidic linkage was observed. 3. The activities of glucose-6-phosphatase and amylo-1,6-glucosidase in the cerebral cortex, liver and myocardium were well preserved. The activities of acid maltase in the three organs mentioned above and of neutral maltase in the myocardium were elevated twice and one and half times more than the control. Phosphorylase levels in the myocardium were extremely small, while in the cerebral cortex and liver normal activities were observed. In light of these findings, glycogen metabolism in Lafora disease is discussed.", "contents": "Biochemical studies on tissues from a patient with Lafora disease. Tissues from the cerebral cortex, liver and myocardium of a patient with Lafora disease were obtained at autopsy and were studied biochemically. 1. Glucose content in the myocardium and liver was almost nil while that in the controls was 0.66 mg/g wet weight in the former and 8.80 mg/g wet weight in the latter. Glycogen content in the cerebral cortex and myocardium was about 10 and 3 times more than in controls. 2. Polyglucosan extracted from the cerebral cortex, liver and myocardium had a longer exterior glucose chain than that in the liver of the control but a normal, alpha or beta 1,4-glucosidic linkage was observed. 3. The activities of glucose-6-phosphatase and amylo-1,6-glucosidase in the cerebral cortex, liver and myocardium were well preserved. The activities of acid maltase in the three organs mentioned above and of neutral maltase in the myocardium were elevated twice and one and half times more than the control. Phosphorylase levels in the myocardium were extremely small, while in the cerebral cortex and liver normal activities were observed. In light of these findings, glycogen metabolism in Lafora disease is discussed."} {"id": "PMID:170015", "title": "[Ultrastructural observations of the velamentous astrocyte impregnated by Golgi's method].", "content": "Electron microscopy of the velamentous astrocyte in the cat inferior colliculus was performed on serial semi-thin and ultra-thin Golgi preparations. The glial origin of the velum has been considered and its topographical relationships with the other structures of the neuropile have been described.", "contents": "[Ultrastructural observations of the velamentous astrocyte impregnated by Golgi's method]. Electron microscopy of the velamentous astrocyte in the cat inferior colliculus was performed on serial semi-thin and ultra-thin Golgi preparations. The glial origin of the velum has been considered and its topographical relationships with the other structures of the neuropile have been described."} {"id": "PMID:170020", "title": "Effects of apolipoproteins on lipoprotein lipase activity of human adipose tissue.", "content": "The effect of apolipoproteins isolated from HDL and VLDL on the activity of lipoprotein lipase (LPL) of adipose tissue was studied. The CII apoprotein was found to activate LPL. This activation was strongly inhibited by CI, AI (apo-Lp-Gln I), and the arginine-rich apoprotein, whereas AII and CIII exhibited a considerably lower inhibitor effect.", "contents": "Effects of apolipoproteins on lipoprotein lipase activity of human adipose tissue. The effect of apolipoproteins isolated from HDL and VLDL on the activity of lipoprotein lipase (LPL) of adipose tissue was studied. The CII apoprotein was found to activate LPL. This activation was strongly inhibited by CI, AI (apo-Lp-Gln I), and the arginine-rich apoprotein, whereas AII and CIII exhibited a considerably lower inhibitor effect."} {"id": "PMID:170021", "title": "Biochemical typing of hyperlipoproteinemia. The development of a nomogram.", "content": "The accurate biochemical typing of hyperlipoproteinemia would require quantification of lipoprotein fractions. At present, typing is frequently based on the lipoprotein electrophoresis pattern together with serum lipid analyses. Lack of facilities for lipoprotein electrophoresis has however focused the clinical interest for classification of hyperlipoproteinemia into other means of a simple biochemical typing. In the present study a nomogram was developed to allow biochemical typing of hyperlipoproteinemia from serum cholesterol and triglyceride values. Serum cholesterol was determined according to a Liebermann-Burchard reaction by the method of Cramer and Isaksson [1], serum triglycerides by the determination of glyceride glycerol according to Carlson [2], and serum lipoprotein electrophoresis was performed on agarose gel [3]. Cholesterol content [4] of alpha-lipoproteins (\"alpha-LP cholesterol\") was obtained in serum after the precipitation of very-low-density lipoproteins(VLDL) and low-density lipoproteins(LDL) by manganese chloride and heparin [5]. Preparative ultracentrifugation was performed in a one-step, gradient procedure [6] isolating VLDL, d less than 1.006, LDL, d 1.006--1.063 g/ml and high-density lipoprotein (HDL) including very-high-density lipoproteins, d greater than 1.063 g/ml, or alternatively at d 1.006 g/ml according to the procedure by Gustafson et al. [7].", "contents": "Biochemical typing of hyperlipoproteinemia. The development of a nomogram. The accurate biochemical typing of hyperlipoproteinemia would require quantification of lipoprotein fractions. At present, typing is frequently based on the lipoprotein electrophoresis pattern together with serum lipid analyses. Lack of facilities for lipoprotein electrophoresis has however focused the clinical interest for classification of hyperlipoproteinemia into other means of a simple biochemical typing. In the present study a nomogram was developed to allow biochemical typing of hyperlipoproteinemia from serum cholesterol and triglyceride values. Serum cholesterol was determined according to a Liebermann-Burchard reaction by the method of Cramer and Isaksson [1], serum triglycerides by the determination of glyceride glycerol according to Carlson [2], and serum lipoprotein electrophoresis was performed on agarose gel [3]. Cholesterol content [4] of alpha-lipoproteins (\"alpha-LP cholesterol\") was obtained in serum after the precipitation of very-low-density lipoproteins(VLDL) and low-density lipoproteins(LDL) by manganese chloride and heparin [5]. Preparative ultracentrifugation was performed in a one-step, gradient procedure [6] isolating VLDL, d less than 1.006, LDL, d 1.006--1.063 g/ml and high-density lipoprotein (HDL) including very-high-density lipoproteins, d greater than 1.063 g/ml, or alternatively at d 1.006 g/ml according to the procedure by Gustafson et al. [7]."} {"id": "PMID:170016", "title": "[Influence of dibutyryl cyclic AMP and theophylline on the frequency of nuclear microtubules and microfilaments of sympathetic neurons].", "content": "In vivo dibutyryl cyclic AMP and theophylline, as does electrical stimulation, increase the frequency of nuclear microtubules and microfilaments in neurons of cat stellate ganglia. These and previous results lead us to conclude that cyclic AMP mediates the process of assembly of these two structural components from preformed protein subunits and thus triggers the formation of highly organized nuclear inclusions corresponding to the so-called intranuclear rodlets of light microscopy.", "contents": "[Influence of dibutyryl cyclic AMP and theophylline on the frequency of nuclear microtubules and microfilaments of sympathetic neurons]. In vivo dibutyryl cyclic AMP and theophylline, as does electrical stimulation, increase the frequency of nuclear microtubules and microfilaments in neurons of cat stellate ganglia. These and previous results lead us to conclude that cyclic AMP mediates the process of assembly of these two structural components from preformed protein subunits and thus triggers the formation of highly organized nuclear inclusions corresponding to the so-called intranuclear rodlets of light microscopy."} {"id": "PMID:170017", "title": "[Inactivation of enteroviruses in seawater].", "content": "Virus survival in the laboratory was examined in non sterile and sterile seawater. Five enteric viruses were studied (Poliovirus, Coxsackie A and B) at four temperatures 4, 12, 22, 37 degrees. Thirty to forty days were required for a 3 log (99.9%) reduction at 22 degrees C, without regard to the virus type, in sterile seawater. Survival times were longer at lower temperatures, but shorter in non sterile seawater. A correlation between virus inactivation and particles of natural seawaters was suggested.", "contents": "[Inactivation of enteroviruses in seawater]. Virus survival in the laboratory was examined in non sterile and sterile seawater. Five enteric viruses were studied (Poliovirus, Coxsackie A and B) at four temperatures 4, 12, 22, 37 degrees. Thirty to forty days were required for a 3 log (99.9%) reduction at 22 degrees C, without regard to the virus type, in sterile seawater. Survival times were longer at lower temperatures, but shorter in non sterile seawater. A correlation between virus inactivation and particles of natural seawaters was suggested."} {"id": "PMID:170024", "title": "Variability of polymorphic cellular enzymes in medical students with different serum lipid levels: a preliminary survey.", "content": "Groups of male Caucasian medical students who had, relative to their classmates, eitherhigh or low lipid levels were screened for electrophoretic variants of haptoglobin, transferrin, and 10 polymorphic erythrocyte enzymes. Members of both the \"high\" and \"low\" lipid groups were found to be polymorphic at 7 genetic loci, 6 of which were enzymatic. Consistently, at most polymorphic loci the high lipid groups had somewhat higher frequencies of nonpredominant phenotypes (patterns other than the phenotype reported to occur most frequently in U.S.A. Caucasian populations). A higher frequency of the less common nonpredominant phenotypes (reported Caucasian population frequency less than 0.200) in the high lipid groups was primarily responsible for the observed variations in the phenotypic distributions. Gene frequency distributions were correspondingly skewed. In 14 comparisons between the high and low lipid groups the least common allele of the 7 polymorphic series had a higher frequency in the high lipid group 9 times and in the low lipid group only once. Collectively, our preliminary observations suggest quantitative and qualitative genetic trends related to serum lipid levels that warrant more extensive investigation.", "contents": "Variability of polymorphic cellular enzymes in medical students with different serum lipid levels: a preliminary survey. Groups of male Caucasian medical students who had, relative to their classmates, eitherhigh or low lipid levels were screened for electrophoretic variants of haptoglobin, transferrin, and 10 polymorphic erythrocyte enzymes. Members of both the \"high\" and \"low\" lipid groups were found to be polymorphic at 7 genetic loci, 6 of which were enzymatic. Consistently, at most polymorphic loci the high lipid groups had somewhat higher frequencies of nonpredominant phenotypes (patterns other than the phenotype reported to occur most frequently in U.S.A. Caucasian populations). A higher frequency of the less common nonpredominant phenotypes (reported Caucasian population frequency less than 0.200) in the high lipid groups was primarily responsible for the observed variations in the phenotypic distributions. Gene frequency distributions were correspondingly skewed. In 14 comparisons between the high and low lipid groups the least common allele of the 7 polymorphic series had a higher frequency in the high lipid group 9 times and in the low lipid group only once. Collectively, our preliminary observations suggest quantitative and qualitative genetic trends related to serum lipid levels that warrant more extensive investigation."} {"id": "PMID:170026", "title": "A competitive protein binding radioassay for 17alpha-ethynylestradiol in human plasma.", "content": "A competitive protein binding radioassay system using a rabbit uterine cytosol preparation for the measurement of ethynylestradiol [EE2e] in human plasma has been developed. Sephadex LH-20 column chromatography is used for the separation of the estrogens prior to assay. EE2 levels were measured in 23 normotensive subjects on contraceptive pills containing either 50 mug of EE2 or mestranol. The EE2 values ranged from 144 to 248 pg with a mean of 211 pg (S.D. +/- 37.94). The method is sensitive enough to detect 25 pg of EE2 in plasma. The intra- and inter-assay coefficients of variation were 7.54% and 10.75%, respectively. Water blanks and plasma blanks from subjects not on pills gave negligible readings for EE2.", "contents": "A competitive protein binding radioassay for 17alpha-ethynylestradiol in human plasma. A competitive protein binding radioassay system using a rabbit uterine cytosol preparation for the measurement of ethynylestradiol [EE2e] in human plasma has been developed. Sephadex LH-20 column chromatography is used for the separation of the estrogens prior to assay. EE2 levels were measured in 23 normotensive subjects on contraceptive pills containing either 50 mug of EE2 or mestranol. The EE2 values ranged from 144 to 248 pg with a mean of 211 pg (S.D. +/- 37.94). The method is sensitive enough to detect 25 pg of EE2 in plasma. The intra- and inter-assay coefficients of variation were 7.54% and 10.75%, respectively. Water blanks and plasma blanks from subjects not on pills gave negligible readings for EE2."} {"id": "PMID:170027", "title": "Hypothalamic hormone interaction in acromegaly.", "content": "The growth hormone response to the administration of the currently available synthetic hypothalamic hormones was assessed in eleven patients with acromegaly. Eight of them showed a positive GH response to thyrotrophin releasing hormone and three showed no response. The GH response to TRH was shown to be unrelated to the thyrotrophin response to TRH. The GH response to TRH was inhibited by the administration of growth hormone release inhibiting hormone. Luteinizing hormone/follicle stimulating hormone releasing hormone (LHRH) caused a positive GH response in four patients, but this was trivial in three. The TRH mediated GH release in acromegaly is not mediated via TSH and appears to be attributable to loss of specificity of the receptor sites on the somatotroph to the hypothalamic hormones.", "contents": "Hypothalamic hormone interaction in acromegaly. The growth hormone response to the administration of the currently available synthetic hypothalamic hormones was assessed in eleven patients with acromegaly. Eight of them showed a positive GH response to thyrotrophin releasing hormone and three showed no response. The GH response to TRH was shown to be unrelated to the thyrotrophin response to TRH. The GH response to TRH was inhibited by the administration of growth hormone release inhibiting hormone. Luteinizing hormone/follicle stimulating hormone releasing hormone (LHRH) caused a positive GH response in four patients, but this was trivial in three. The TRH mediated GH release in acromegaly is not mediated via TSH and appears to be attributable to loss of specificity of the receptor sites on the somatotroph to the hypothalamic hormones."} {"id": "PMID:170028", "title": "Malignant metastatic insulinoma treated with streptozotocin.", "content": "A patient with metastatic insulinoma who suffered from severe hypoglycaemic attacks was treated with 7-5 g of streptozotocin (Upjohn). Shortly after the start of treatment, the hypoglycaemic attacks ceased; fasting blood glucose levels and serum immunoreactive insulin values returned to normal upon completion of the treatment. Two years after treatment, the patient is well and active and has not had any attacks. The oral glucose tolerance test and tolbutamide stimulation test now show serum immunoreactive insulin excretion patterns similar to those seen in diabetics.", "contents": "Malignant metastatic insulinoma treated with streptozotocin. A patient with metastatic insulinoma who suffered from severe hypoglycaemic attacks was treated with 7-5 g of streptozotocin (Upjohn). Shortly after the start of treatment, the hypoglycaemic attacks ceased; fasting blood glucose levels and serum immunoreactive insulin values returned to normal upon completion of the treatment. Two years after treatment, the patient is well and active and has not had any attacks. The oral glucose tolerance test and tolbutamide stimulation test now show serum immunoreactive insulin excretion patterns similar to those seen in diabetics."} {"id": "PMID:170030", "title": "Detection of inborn errors of metabolism. IV. Galactokinase deficiency.", "content": "Galactokinase deficient fibroblasts are not distinguishable from galactosemic fibroblasts by a test suggested earlier by Hill & Puck (1973). They can be so distinguished by the test described here, since they are unable to incorporate radioactive galactose into TCA-insoluble material under normal conditions of incubation while both galactosemic and normal cells incorporate considerable amounts. The importance of this is discussed in relationship to antenatal screening.", "contents": "Detection of inborn errors of metabolism. IV. Galactokinase deficiency. Galactokinase deficient fibroblasts are not distinguishable from galactosemic fibroblasts by a test suggested earlier by Hill & Puck (1973). They can be so distinguished by the test described here, since they are unable to incorporate radioactive galactose into TCA-insoluble material under normal conditions of incubation while both galactosemic and normal cells incorporate considerable amounts. The importance of this is discussed in relationship to antenatal screening."} {"id": "PMID:170031", "title": "Further studies of Lp(a) lipoprotein/pre- beta1-lipoprotein in patients with coronary heart disease.", "content": "The present study of 100 patients (46 of whom were included in a previous study) with suspected or proven coronary heart disease (CHD) confirms that Lp(a) lipoprotein and pre-beta1-lipoprotein are closely related, if not identical, and that Lp(a) lipoprotein/pre-beta-lipoprotein occurs more frequently in patients with CHD than in healthy people. Analysis of this lipoprotein component may have predictive value with respect to CHD.", "contents": "Further studies of Lp(a) lipoprotein/pre- beta1-lipoprotein in patients with coronary heart disease. The present study of 100 patients (46 of whom were included in a previous study) with suspected or proven coronary heart disease (CHD) confirms that Lp(a) lipoprotein and pre-beta1-lipoprotein are closely related, if not identical, and that Lp(a) lipoprotein/pre-beta-lipoprotein occurs more frequently in patients with CHD than in healthy people. Analysis of this lipoprotein component may have predictive value with respect to CHD."} {"id": "PMID:170032", "title": "Pituitary-adrenal response to static exercise in man.", "content": "1. Changes in plasma concentrations of catecholamines and cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma cortisol increased after the subject pushed for 3 min at 50% of maximum force. 2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma cortisol and in plasma ACTH but no changes in growth hormone were observed.", "contents": "Pituitary-adrenal response to static exercise in man. 1. Changes in plasma concentrations of catecholamines and cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma cortisol increased after the subject pushed for 3 min at 50% of maximum force. 2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma cortisol and in plasma ACTH but no changes in growth hormone were observed."} {"id": "PMID:170035", "title": "Dispersion along fiber tracts and in the coupling between tracts and a cortical network.", "content": "Dispersion in a neuronal coritcal network was modeled using CSMP, a Continuous Systems Modeling Program. The signal dispersion over pathways was simulated by use of a serial product approximating the convolution integral. The program was written in a sufficiently general format to be applied to a variety of biological signals. Calculated signals from a fiber tract and activation of a cortical network were compared with experimental data from cats. The network consists of excitatory cells in a forward limb which send collaterals to interneurons that, once excited, feed back to inhibit the excitatory cells. The model was consistent with data from neuronal assemblies in the prepyriform cortex and fibers in the lateral olfactory tract.", "contents": "Dispersion along fiber tracts and in the coupling between tracts and a cortical network. Dispersion in a neuronal coritcal network was modeled using CSMP, a Continuous Systems Modeling Program. The signal dispersion over pathways was simulated by use of a serial product approximating the convolution integral. The program was written in a sufficiently general format to be applied to a variety of biological signals. Calculated signals from a fiber tract and activation of a cortical network were compared with experimental data from cats. The network consists of excitatory cells in a forward limb which send collaterals to interneurons that, once excited, feed back to inhibit the excitatory cells. The model was consistent with data from neuronal assemblies in the prepyriform cortex and fibers in the lateral olfactory tract."} {"id": "PMID:170036", "title": "Sorting of signals from thermosensitive areas.", "content": "Of the several models proposed for the neural regulation of temperature in cold-exposed animals, two have been previously restated in dynamic form using CSMP. Subsequently, computer simulations have led to the design and execution of experiments for selection of the more appropriate model for cold-exposed rats. These experiments, as described in the present paper, have been interpreted as being consistent with the model which sorts signals from thermosensitive areas and channels the selected signals over separate neural pathways to independently control each mode of heat production. Since this model requires multiplication of neural signals, possible neuronal mechanisms which may underline such multiplication are discussed. In addition, parameter variation to account for febril responses and rate sensitivity have been evaluated.", "contents": "Sorting of signals from thermosensitive areas. Of the several models proposed for the neural regulation of temperature in cold-exposed animals, two have been previously restated in dynamic form using CSMP. Subsequently, computer simulations have led to the design and execution of experiments for selection of the more appropriate model for cold-exposed rats. These experiments, as described in the present paper, have been interpreted as being consistent with the model which sorts signals from thermosensitive areas and channels the selected signals over separate neural pathways to independently control each mode of heat production. Since this model requires multiplication of neural signals, possible neuronal mechanisms which may underline such multiplication are discussed. In addition, parameter variation to account for febril responses and rate sensitivity have been evaluated."} {"id": "PMID:170037", "title": "The distribution of collagenase in the rat uterus during postpartum involution. An immunohistochemical study.", "content": "A monospecific rabbit anti-rat uterus collagenase antibody has been prepared and used to study the distribution of the enzyme in the rat uterus during postpartum involution. Cryostat sections of rat uteri from 24 to 240 hours postpartum were stained by the indirect immunofluorescent method. Nonpregnant rat uterus revelaed positive staining in basement membranes, in endometrial stroma, in perimuscular and in vascular connective tissue. During postpartum involution of the uterus two types of changes in uterine collagenase were observed: (1) variations in the distrubiton of the enzyme, which became selectively localized in the epithelial basement membrane and in the wall of small blood vessels, and (2) variations in the overall intensity of fluorescent staining, which decreased immediately after delivery and slowly increased back to nonpregnant levels in 5 days. The significance of these findings is discussed in relation to the mechanisms of control of collagenase activity in vivo.", "contents": "The distribution of collagenase in the rat uterus during postpartum involution. An immunohistochemical study. A monospecific rabbit anti-rat uterus collagenase antibody has been prepared and used to study the distribution of the enzyme in the rat uterus during postpartum involution. Cryostat sections of rat uteri from 24 to 240 hours postpartum were stained by the indirect immunofluorescent method. Nonpregnant rat uterus revelaed positive staining in basement membranes, in endometrial stroma, in perimuscular and in vascular connective tissue. During postpartum involution of the uterus two types of changes in uterine collagenase were observed: (1) variations in the distrubiton of the enzyme, which became selectively localized in the epithelial basement membrane and in the wall of small blood vessels, and (2) variations in the overall intensity of fluorescent staining, which decreased immediately after delivery and slowly increased back to nonpregnant levels in 5 days. The significance of these findings is discussed in relation to the mechanisms of control of collagenase activity in vivo."} {"id": "PMID:170040", "title": "Oxidation of reduced nicotinamide adenine dinucleotide by particles from Mycobacterium lepraemurium.", "content": "Particles from Mycobacterium lepraemurium catalysed the oxidation of NADH with oxygen as the terminal electron acceptor. The preparations contained cytochromes of the a + a3'b and c types, as well as CO-binding pigments. The NADH oxidase activity was sensitive to inhibitors of the flavoprotein system as well as to HQNO and antimycin A. In addition, a cytochrome oxidase sensitive to cyanide was also present. The system was inhibited by the thiol-binding agent, PCMB, and thus indicated the involvement of sulphydryl group in the enzymatic oxidation of NADH. The sensitivity of the NADH oxidase system to all the inhibitors of the respiratory chain and the effect of these inhibitors on the absorption spectra suggested that cytochromes of the b, c, a + a3 types are involved in the transfer of electrons in NADH oxidation.", "contents": "Oxidation of reduced nicotinamide adenine dinucleotide by particles from Mycobacterium lepraemurium. Particles from Mycobacterium lepraemurium catalysed the oxidation of NADH with oxygen as the terminal electron acceptor. The preparations contained cytochromes of the a + a3'b and c types, as well as CO-binding pigments. The NADH oxidase activity was sensitive to inhibitors of the flavoprotein system as well as to HQNO and antimycin A. In addition, a cytochrome oxidase sensitive to cyanide was also present. The system was inhibited by the thiol-binding agent, PCMB, and thus indicated the involvement of sulphydryl group in the enzymatic oxidation of NADH. The sensitivity of the NADH oxidase system to all the inhibitors of the respiratory chain and the effect of these inhibitors on the absorption spectra suggested that cytochromes of the b, c, a + a3 types are involved in the transfer of electrons in NADH oxidation."} {"id": "PMID:170041", "title": "Phosphorylation of DNA polymerase.", "content": "Both E. coli and calf thymus DNA polymerase can be phosphorylated by cAMP-dependent protein kinase and phosphorylation appears to stimulate the DNA polymerase reaction. Conversely, dephosphorylation of the polymerase molecule, by a protein phosphatase, inhibits the polymerase reaction.", "contents": "Phosphorylation of DNA polymerase. Both E. coli and calf thymus DNA polymerase can be phosphorylated by cAMP-dependent protein kinase and phosphorylation appears to stimulate the DNA polymerase reaction. Conversely, dephosphorylation of the polymerase molecule, by a protein phosphatase, inhibits the polymerase reaction."} {"id": "PMID:170043", "title": "Prevention of acute pulmonary edema during isolated perfusion for 24 hours.", "content": "Fifty-nine canine lungs were perfused with cryoprecipitated plasma, silica gel fraction, or modified silica gel fraction (MSGF) af different perfusate pressures for periods up to 24 hours under hypothermic conditions. High perfusate pressures accounted for all poor perfusion results. The use of MSGF at a low perfusate pressure protected all the lungs from the appearance of pulmonary edema during perfusion, and the morphology was consistently maintained for 24 hours.", "contents": "Prevention of acute pulmonary edema during isolated perfusion for 24 hours. Fifty-nine canine lungs were perfused with cryoprecipitated plasma, silica gel fraction, or modified silica gel fraction (MSGF) af different perfusate pressures for periods up to 24 hours under hypothermic conditions. High perfusate pressures accounted for all poor perfusion results. The use of MSGF at a low perfusate pressure protected all the lungs from the appearance of pulmonary edema during perfusion, and the morphology was consistently maintained for 24 hours."} {"id": "PMID:170044", "title": "Malignant mediastinal chemodectoma.", "content": "A 20-year-old man with a posterior mediastinal mass and erosion of the rib proved to have a malignant chemodectoma. The case is of interest because of the rare location and malignant fatal course.", "contents": "Malignant mediastinal chemodectoma. A 20-year-old man with a posterior mediastinal mass and erosion of the rib proved to have a malignant chemodectoma. The case is of interest because of the rare location and malignant fatal course."} {"id": "PMID:170045", "title": "Inappropriate secretion of antidiuretic hormone associated with adenovirus pneumonia.", "content": "Metabolic abnormalities compatible with inappropriate secretion of ADH developed during the course of severe viral pneumonia in a 17-year-old Navy recruit. With a regimen of strict fluid restriction, normalization of these abnormalities occurred. Marked leukopenia and hypoxia were also present, but gradually improved with resolution of the pneumonia. Inappropriate ADH secretion has been associated most often with bacterial pneumonia and this patient represents one of the few with viral pneumonia complicated by this syndrome. While the previous cases were assoicated with influenza virus, this patient was infected with adenovirus-7 which is endemic in the military recruit population.", "contents": "Inappropriate secretion of antidiuretic hormone associated with adenovirus pneumonia. Metabolic abnormalities compatible with inappropriate secretion of ADH developed during the course of severe viral pneumonia in a 17-year-old Navy recruit. With a regimen of strict fluid restriction, normalization of these abnormalities occurred. Marked leukopenia and hypoxia were also present, but gradually improved with resolution of the pneumonia. Inappropriate ADH secretion has been associated most often with bacterial pneumonia and this patient represents one of the few with viral pneumonia complicated by this syndrome. While the previous cases were assoicated with influenza virus, this patient was infected with adenovirus-7 which is endemic in the military recruit population."} {"id": "PMID:170048", "title": "The volume and DNA content of extrachromosomal inclusions in the dorsal foot-pad nuclei of Tricholioproctia impatiens (Sarcophagidae, Diptera).", "content": "The chromosomes of the giant dorsal foot-pad cells of Tricholioproctia impatiens produce numerous extrachromosomal bodies which consist of a central spherical core of DNA surrounded by a ribonucleoprotein layer. The bodies are either free within the nucleoplasm or attached by thin threads of chromatin to chromosomal bands. The DNA content and the volume of DNA of unattached spherules fell into distinct classes in a regular geometric progression.", "contents": "The volume and DNA content of extrachromosomal inclusions in the dorsal foot-pad nuclei of Tricholioproctia impatiens (Sarcophagidae, Diptera). The chromosomes of the giant dorsal foot-pad cells of Tricholioproctia impatiens produce numerous extrachromosomal bodies which consist of a central spherical core of DNA surrounded by a ribonucleoprotein layer. The bodies are either free within the nucleoplasm or attached by thin threads of chromatin to chromosomal bands. The DNA content and the volume of DNA of unattached spherules fell into distinct classes in a regular geometric progression."} {"id": "PMID:170051", "title": "[In vivo dissolving of gall-stones: the effect of chenodeoxycholic acid. (author's transl)].", "content": "Chenodeoxycholic acid (CDCA) was administered for an average of 15 months to 14 patients with gall-stones. The gall-stones were radiolucent in all but one instance (solitary calcified stone). Stones dissolved completely after 12 and 15 months of therapy, respectively, in two patients, while in four the size of the stones diminished. No change occurred in the remaining patients. In five patients multiple stones dissolved, while in one a radiolucent solitary stone dissolved. In one patient, with a negative cholecystogram for a time before being treated with CDCA, the gall-bladder perforated while on treatment. CDCA was well tolerated by all patients: upper abdominal discomfort disappeared during CDCA treatment in two patients and improved in nine. Only side-effect was occasional mild diarrhoea in five patients. Bile was analysed in seven patients, supersaturation with cholesterol being found in five. Biliary lipid composition became normal during CDCA treatment in these five patients. Serum triglyceride levels fell during CDCA administration in ten of eleven patients in which serum measurements were made; the greatest fall occurred in the five patients with hypertriglyceridaemia. The fall in triglyceride levels was associated with a diminution of the pre-beta-lipo-protein fraction and the chylomicron fraction. No significant change occurred in serum cholesterol levels.", "contents": "[In vivo dissolving of gall-stones: the effect of chenodeoxycholic acid. (author's transl)]. Chenodeoxycholic acid (CDCA) was administered for an average of 15 months to 14 patients with gall-stones. The gall-stones were radiolucent in all but one instance (solitary calcified stone). Stones dissolved completely after 12 and 15 months of therapy, respectively, in two patients, while in four the size of the stones diminished. No change occurred in the remaining patients. In five patients multiple stones dissolved, while in one a radiolucent solitary stone dissolved. In one patient, with a negative cholecystogram for a time before being treated with CDCA, the gall-bladder perforated while on treatment. CDCA was well tolerated by all patients: upper abdominal discomfort disappeared during CDCA treatment in two patients and improved in nine. Only side-effect was occasional mild diarrhoea in five patients. Bile was analysed in seven patients, supersaturation with cholesterol being found in five. Biliary lipid composition became normal during CDCA treatment in these five patients. Serum triglyceride levels fell during CDCA administration in ten of eleven patients in which serum measurements were made; the greatest fall occurred in the five patients with hypertriglyceridaemia. The fall in triglyceride levels was associated with a diminution of the pre-beta-lipo-protein fraction and the chylomicron fraction. No significant change occurred in serum cholesterol levels."} {"id": "PMID:170052", "title": "[Lipoprotein pattern in acute and chronic liver disease (author's transl)].", "content": "Lipoprotein electrophoresis with measurement of serum lipids was performed on 115 patients with various forms of liver disease. There was a reduction in alpha-lipoproteins and an increase in beta-lipoproteins, as well as a reduced separability of pre-beta and beta fractions in those with acute viral hepatitis. All these changes regressed completely with healing. Similar changes were shown also in chronic liver disease and were most marked in acute liver failure, but also marked in decompensated liver cirrhosis and chronic progressive hepatitis, while less marked in chronic persistent hepatitis and compensated liver cirrhosis. In patients with fatty livers there were no characteristic findings other than a slight increase in pre-beta lipoproteins. On the other hand, the lipoprotein pattern was markedly changed in cases with tumour in the region of the gallbladder, but similar changes were noted also with tumours at other sites. They are, therfore, unlikely to be liver-specific.", "contents": "[Lipoprotein pattern in acute and chronic liver disease (author's transl)]. Lipoprotein electrophoresis with measurement of serum lipids was performed on 115 patients with various forms of liver disease. There was a reduction in alpha-lipoproteins and an increase in beta-lipoproteins, as well as a reduced separability of pre-beta and beta fractions in those with acute viral hepatitis. All these changes regressed completely with healing. Similar changes were shown also in chronic liver disease and were most marked in acute liver failure, but also marked in decompensated liver cirrhosis and chronic progressive hepatitis, while less marked in chronic persistent hepatitis and compensated liver cirrhosis. In patients with fatty livers there were no characteristic findings other than a slight increase in pre-beta lipoproteins. On the other hand, the lipoprotein pattern was markedly changed in cases with tumour in the region of the gallbladder, but similar changes were noted also with tumours at other sites. They are, therfore, unlikely to be liver-specific."} {"id": "PMID:170053", "title": "Antibacterial Drugs today: II.", "content": "Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism. This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs. With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed. Part II of the review discusses the cephalosporins, polymyxins and aminoglycosides. The place of each in therapy is defined.", "contents": "Antibacterial Drugs today: II. Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism. This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs. With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed. Part II of the review discusses the cephalosporins, polymyxins and aminoglycosides. The place of each in therapy is defined."} {"id": "PMID:170055", "title": "Fish gonadotropin(s). I. Bioassay of salmon gonadotropin(s) in vitro with immature trout gonads.", "content": "1. The effect of salmon gonadotropin(s) (SG) on cyclic AMP (cAMP) levels in immature trout gonadal tissue of both sexes was measured by radioimmunoassay. 2. A dose-response line was obtained to SG in gonads of both male and female trout. 3. As little as 0.45 SG units (1 SG unit = 1 mug NIH-LH-S18 in the chick bioassay) significantly increased cAMP formation in the presence of 8 mM theophylline; mammalian LH, FSH, LTH, ACTH, TSH and HCG were inactive. 4. The assay for SG was investigated with respect to time of incubation and two phosphodiesterase inhibitors; some conditions for the cAMP radioimmunoassay (cAMP-RIA) were compared.", "contents": "Fish gonadotropin(s). I. Bioassay of salmon gonadotropin(s) in vitro with immature trout gonads. 1. The effect of salmon gonadotropin(s) (SG) on cyclic AMP (cAMP) levels in immature trout gonadal tissue of both sexes was measured by radioimmunoassay. 2. A dose-response line was obtained to SG in gonads of both male and female trout. 3. As little as 0.45 SG units (1 SG unit = 1 mug NIH-LH-S18 in the chick bioassay) significantly increased cAMP formation in the presence of 8 mM theophylline; mammalian LH, FSH, LTH, ACTH, TSH and HCG were inactive. 4. The assay for SG was investigated with respect to time of incubation and two phosphodiesterase inhibitors; some conditions for the cAMP radioimmunoassay (cAMP-RIA) were compared."} {"id": "PMID:170056", "title": "Fish gonadotropin(s). II. Isolation of gonadotropin(s) from chum salmon pituitary glands using affinity chromatography.", "content": "A highly purified gonadotropic hormone preparation has been obtained from chum salmon (Oncorhynchus keta) pituitaries by extraction with ethanolic or aqueous buffer, affinity chromatography on Con A Sepharose and gel filtration on Sephadex G-75 superfine. A purified fraction from Sephadex G-75 averaged 448 mug NIH-LH-S18/mg glycoprotein as measured by the uptake of radiophosphate into chick testes. A total of 1.1 g of salmon gonadotropin (s) (SG)/kg fresh tissue was recovered when the isolation began with an aqueous extraction. Analytical polyacrylamide gel electrophoresis (P.A.G.E.) of the purified fraction from Sephadex G-75 displayed a single broad zone in non-dissociating conditions and two bands in 8 M urea. Polyacrylamide gel electrofocusing yielded six sharp bands with an isoelectric point range of 4.38 to 5.05, and four bands with an isoelectric point range of 4.31 to 4.95 in 8 M urea. A molecular weight of 41,000 was determined by gel filtration. A subunit molecular weight of 17,800 +/- 10% was found by P.A.G.E. in 0.1% sodium dodecyl sulphate (SDS), suggesting that native SG consists of two subunits. Purified preparations were highly stable in Tris-Cl buffers and retained their activity for several months when stored at -73 degrees C.", "contents": "Fish gonadotropin(s). II. Isolation of gonadotropin(s) from chum salmon pituitary glands using affinity chromatography. A highly purified gonadotropic hormone preparation has been obtained from chum salmon (Oncorhynchus keta) pituitaries by extraction with ethanolic or aqueous buffer, affinity chromatography on Con A Sepharose and gel filtration on Sephadex G-75 superfine. A purified fraction from Sephadex G-75 averaged 448 mug NIH-LH-S18/mg glycoprotein as measured by the uptake of radiophosphate into chick testes. A total of 1.1 g of salmon gonadotropin (s) (SG)/kg fresh tissue was recovered when the isolation began with an aqueous extraction. Analytical polyacrylamide gel electrophoresis (P.A.G.E.) of the purified fraction from Sephadex G-75 displayed a single broad zone in non-dissociating conditions and two bands in 8 M urea. Polyacrylamide gel electrofocusing yielded six sharp bands with an isoelectric point range of 4.38 to 5.05, and four bands with an isoelectric point range of 4.31 to 4.95 in 8 M urea. A molecular weight of 41,000 was determined by gel filtration. A subunit molecular weight of 17,800 +/- 10% was found by P.A.G.E. in 0.1% sodium dodecyl sulphate (SDS), suggesting that native SG consists of two subunits. Purified preparations were highly stable in Tris-Cl buffers and retained their activity for several months when stored at -73 degrees C."} {"id": "PMID:170057", "title": "Fish gonadotropin(s). III. Evidence for more than one gonadotropin in chum salmon pituitary glands.", "content": "Two proteins with gonadotropin activity have been isolated from a highly purified chum salmon (Oncorhynchus keta) gonadotropin preparation (G-75 Fraction II) by chromatography on DEAE Bio Gel A. These gonadotropins exhibited distinct behaviour in polyacrylamide gel electrophoresis, chromatography on Sephadex G-75 superfine, and ratios of cAMP stimulation in immature rainbow trout ovaries and testes. Rechromatography of G-75 Fraction II on Sephadex G-75 superfine gave a symmetrical protein peak with a coincident cAMP activity profile. Repeated freezing and thawing elicited a shift in the cAMP activity profile toward the trailing edge of the protein peak. Data are discussed in terms of two gonadotropin molecules which respond differently to phase changes. Charge polymorphism was exhibited by isoelectric focusing in polyacrylamide gels of one of the DEAE fractions. Five UV absorbing bands were observed which stimulated cAMP production in immature rainbow trout gonads. Three of these bands increased adenyl cyclase activity in trout ovaries and testes. One of the bands stimulated cAMP production primarily in trout testes and the other stimulated trout ovaries, providing evidence for two gonadotropins, each of which is sex specific.", "contents": "Fish gonadotropin(s). III. Evidence for more than one gonadotropin in chum salmon pituitary glands. Two proteins with gonadotropin activity have been isolated from a highly purified chum salmon (Oncorhynchus keta) gonadotropin preparation (G-75 Fraction II) by chromatography on DEAE Bio Gel A. These gonadotropins exhibited distinct behaviour in polyacrylamide gel electrophoresis, chromatography on Sephadex G-75 superfine, and ratios of cAMP stimulation in immature rainbow trout ovaries and testes. Rechromatography of G-75 Fraction II on Sephadex G-75 superfine gave a symmetrical protein peak with a coincident cAMP activity profile. Repeated freezing and thawing elicited a shift in the cAMP activity profile toward the trailing edge of the protein peak. Data are discussed in terms of two gonadotropin molecules which respond differently to phase changes. Charge polymorphism was exhibited by isoelectric focusing in polyacrylamide gels of one of the DEAE fractions. Five UV absorbing bands were observed which stimulated cAMP production in immature rainbow trout gonads. Three of these bands increased adenyl cyclase activity in trout ovaries and testes. One of the bands stimulated cAMP production primarily in trout testes and the other stimulated trout ovaries, providing evidence for two gonadotropins, each of which is sex specific."} {"id": "PMID:170058", "title": "Effect of insulin on metabolism of cyclic adenosine 3',5'-monophosphate by plasma cell tumor (MPC-11).", "content": "Addition of insulin to cultured mouse plasma tumor cells (MPC-11) increases the entry of tritiated cyclic adenosine 3',5'-monophosphate (3H-cAMP). No increase of entry of N6-O2-dibutyryl adenosine 3',5' cyclic monophosphate (DBcAMP), 5' adenosine monophosphate (5' AMP) or adenosine was noted in the presence of insulin. The stimulation of cAMP transport by insulin was concentration dependent and inactivated insulin had no effect on nucleotide transport. Intracellular radioactivity after transport of cAMP was largely 5'AMP, while most of the extracellular radioactivity remained as cAMP after incubation.", "contents": "Effect of insulin on metabolism of cyclic adenosine 3',5'-monophosphate by plasma cell tumor (MPC-11). Addition of insulin to cultured mouse plasma tumor cells (MPC-11) increases the entry of tritiated cyclic adenosine 3',5'-monophosphate (3H-cAMP). No increase of entry of N6-O2-dibutyryl adenosine 3',5' cyclic monophosphate (DBcAMP), 5' adenosine monophosphate (5' AMP) or adenosine was noted in the presence of insulin. The stimulation of cAMP transport by insulin was concentration dependent and inactivated insulin had no effect on nucleotide transport. Intracellular radioactivity after transport of cAMP was largely 5'AMP, while most of the extracellular radioactivity remained as cAMP after incubation."} {"id": "PMID:170059", "title": "Isolation and culture of FSH responsive Sertoli cells.", "content": "Methods for the isolation and culture of enriched populations of Sertoli cells from 20-60 day old rats are described. The identity of the Sertoli cells was verified by bright light and electron microscopy. Freshly isolated Sertoli cells specifically bound follicle stimulating hormone (FSH) but not luteinizing hormone (LH) and responded to FSH stimulation with dramatic increase in cyclic AMP level. Isolated Sertoli cells, maintained in culture for 11 days, showed no evidence of proliferation but retained their characteristic ultrastructural features and FSH binding ability. Incubation of cultured cells with FSH resulted in a significant stimulation of cyclic AMP and androgen binding protein (ABP). Since the freshly isolated or cultured cells were predominantly (greater than 80%) Sertoli cells, these results provide direct evidence that the Sertoli cells represent a primary target site for FSH activity in the testes. The culture method also provides a valuable in vitro model for the study of chronic effects of various agents on the Sertoli cell.", "contents": "Isolation and culture of FSH responsive Sertoli cells. Methods for the isolation and culture of enriched populations of Sertoli cells from 20-60 day old rats are described. The identity of the Sertoli cells was verified by bright light and electron microscopy. Freshly isolated Sertoli cells specifically bound follicle stimulating hormone (FSH) but not luteinizing hormone (LH) and responded to FSH stimulation with dramatic increase in cyclic AMP level. Isolated Sertoli cells, maintained in culture for 11 days, showed no evidence of proliferation but retained their characteristic ultrastructural features and FSH binding ability. Incubation of cultured cells with FSH resulted in a significant stimulation of cyclic AMP and androgen binding protein (ABP). Since the freshly isolated or cultured cells were predominantly (greater than 80%) Sertoli cells, these results provide direct evidence that the Sertoli cells represent a primary target site for FSH activity in the testes. The culture method also provides a valuable in vitro model for the study of chronic effects of various agents on the Sertoli cell."} {"id": "PMID:170060", "title": "Estrogen binding protein of rat liver.", "content": "An estrogen binding protein for estradiol-17beta is present in the liver cytosol of female intact and one day oophorectomized rats. The dissociation constant reveals high affinity binding (Kd: 0.69 +/- 0.14 times 10(-10) M). Quantitation of EBP using a dextran-coated charcoal method shows that this specific macromolecular binding is much less than in the rat uterus, but similar to that in DMBA-induced mammary tumors. Sucrose density gradient analysis shows sedimentation at 8-9 S and 4-5 S when compared to bovine serum albumin.", "contents": "Estrogen binding protein of rat liver. An estrogen binding protein for estradiol-17beta is present in the liver cytosol of female intact and one day oophorectomized rats. The dissociation constant reveals high affinity binding (Kd: 0.69 +/- 0.14 times 10(-10) M). Quantitation of EBP using a dextran-coated charcoal method shows that this specific macromolecular binding is much less than in the rat uterus, but similar to that in DMBA-induced mammary tumors. Sucrose density gradient analysis shows sedimentation at 8-9 S and 4-5 S when compared to bovine serum albumin."} {"id": "PMID:170061", "title": "Demonstration of a specific receptor for prolactin in porcine granulosa cells.", "content": "Porcine granulosa cells and subcellular fractions from these cells have been shown to have a specific receptor for ovine prolactin (OPRL). Ovine growth hormone demonstrated 7% of the potency of OPRL in displacing 125I-OPRL from its binding site; FSH, TSH, LH, insulin and ACTH showed negligible cross-reactivity. Scatchard analysis of the displacement curves suggested that 125I-OPRL has a high affinity for its receptor with a dissociation constant (Kd) for the granulosa cell-receptor of 7.4-7.7 times 10(-10) M with no change as the follicle enlarges. In contrast, the specific binding of prolactin decreased markedly with maturation of the follicles with an apparent decrease in binding sites/cell from 555 in small follicles to 300 in large (preovulatory) follicles. The demonstrated Kd's were within the range of prolactin concentrations easily attained in vivo and were in good agreement with values obtained in our laboratory and elsewhere for the prolactin receptor from mammary gland and other tissues. Consequently, these studies may provide a basis for a better understanding of the role of prolactin in ovarian function.", "contents": "Demonstration of a specific receptor for prolactin in porcine granulosa cells. Porcine granulosa cells and subcellular fractions from these cells have been shown to have a specific receptor for ovine prolactin (OPRL). Ovine growth hormone demonstrated 7% of the potency of OPRL in displacing 125I-OPRL from its binding site; FSH, TSH, LH, insulin and ACTH showed negligible cross-reactivity. Scatchard analysis of the displacement curves suggested that 125I-OPRL has a high affinity for its receptor with a dissociation constant (Kd) for the granulosa cell-receptor of 7.4-7.7 times 10(-10) M with no change as the follicle enlarges. In contrast, the specific binding of prolactin decreased markedly with maturation of the follicles with an apparent decrease in binding sites/cell from 555 in small follicles to 300 in large (preovulatory) follicles. The demonstrated Kd's were within the range of prolactin concentrations easily attained in vivo and were in good agreement with values obtained in our laboratory and elsewhere for the prolactin receptor from mammary gland and other tissues. Consequently, these studies may provide a basis for a better understanding of the role of prolactin in ovarian function."} {"id": "PMID:170062", "title": "Autoradiographic localization of corticosterone receptors (type III) to the collecting tubule of the rat kidney.", "content": "Recently, a class of receptors exhibiting high affinity for corticosterone was described in rat kidney (Feldman, D. et al., Endocrinology 92: 1429, 1973). These receptor sites exhibited negligible affinity for dexamethasone and aldosterone and were designated Type III to distinguish them from sites having high affinity for aldosterone (Type I), and sites with high affinity for dexamethasone and corticosterone (Type II). To visually localize Type III sites in the kidney and demonstrate whether or not they represent intracellular steroid receptors, we used an autoradiographic procedure for diffusible substances. Male adrenalectomized rats were injected intravenously with the following combination of steroids per 100 g body weight: 4 x 10(-9) mol [3H]corticosterone, 4 x 10(-9) mol unlabeled aldosterone, and 4 x 10(-9) mol unlabeled dexamethasone. To differentiate \"nonspecific\" binding, each experimental animal was paired with a control animal that received the same steroids plus 250-fold unlabeled corticosterone. At 3 min, 10 min, and 30 min, kidneys were removed, cut into quadrants, and frozen in isopentane cooled by liquid nitrogen. For autoradiography, 4 mum frozen sections were cut, pressed into contact with emulsion precoated slides at -30 C, melted and simultaneously dried under a jet of dry nitrogen gas, and exposed at 4 C for 2 to 6 weeks. At all three time intervals, silver grains representing [3H]corticosterone binding sites, were concentrated over collecting tubules, only in the outer medulla and cortex (those in the inner medulla and papilla were not labeled). In the labeled segments of the nephron, some of the cells showed an apparent high ratio of cytoplasmic to nuclear grains and in others nuclear labeling was more prominent. A small population of cells within labeled collecting tubules (possibly dark cells) were not labeled. Although no function can yet be ascribed to Type III receptors in the kidney, they may represent an important steroid-mediated renal mechanism.", "contents": "Autoradiographic localization of corticosterone receptors (type III) to the collecting tubule of the rat kidney. Recently, a class of receptors exhibiting high affinity for corticosterone was described in rat kidney (Feldman, D. et al., Endocrinology 92: 1429, 1973). These receptor sites exhibited negligible affinity for dexamethasone and aldosterone and were designated Type III to distinguish them from sites having high affinity for aldosterone (Type I), and sites with high affinity for dexamethasone and corticosterone (Type II). To visually localize Type III sites in the kidney and demonstrate whether or not they represent intracellular steroid receptors, we used an autoradiographic procedure for diffusible substances. Male adrenalectomized rats were injected intravenously with the following combination of steroids per 100 g body weight: 4 x 10(-9) mol [3H]corticosterone, 4 x 10(-9) mol unlabeled aldosterone, and 4 x 10(-9) mol unlabeled dexamethasone. To differentiate \"nonspecific\" binding, each experimental animal was paired with a control animal that received the same steroids plus 250-fold unlabeled corticosterone. At 3 min, 10 min, and 30 min, kidneys were removed, cut into quadrants, and frozen in isopentane cooled by liquid nitrogen. For autoradiography, 4 mum frozen sections were cut, pressed into contact with emulsion precoated slides at -30 C, melted and simultaneously dried under a jet of dry nitrogen gas, and exposed at 4 C for 2 to 6 weeks. At all three time intervals, silver grains representing [3H]corticosterone binding sites, were concentrated over collecting tubules, only in the outer medulla and cortex (those in the inner medulla and papilla were not labeled). In the labeled segments of the nephron, some of the cells showed an apparent high ratio of cytoplasmic to nuclear grains and in others nuclear labeling was more prominent. A small population of cells within labeled collecting tubules (possibly dark cells) were not labeled. Although no function can yet be ascribed to Type III receptors in the kidney, they may represent an important steroid-mediated renal mechanism."} {"id": "PMID:170063", "title": "Effect of porcine calcitonin on the metabolism of calcium and cyclic AMP in rat skeletal tissue in vivo.", "content": "Infusion of 50 mU/100 g body wt of calcitonin induced a rapid and marked increase of cyclic AMP in calvaria as well as in plasma of thyroparathyroidectomized rats. These changes preceded the decrease in plasma calcium concentration seen after hormone administration. The possible relationship of this stimulation of cyclic AMP accumulation to the hypocalcemic effect of calcitonin was examined under several experimental settings. It was found that a dose of calcitonin sufficient to cause a significant decrease of plasma calcium failed to produce any detectable accumulation cyclic AMP in calvaria, but when high doses of calcitonin were given, there was an apparent correlation between the integrated change of cyclic AMP metabolism and the duration and magnitude of hypocalcemia. Experiments employing the ophylline and imidazole, which alter cyclic AMP metabolism, led to an apparent dissociation between the hypocalcemic effect of calcitonin and its stimulation of cyclic AMP accumulation in bone.", "contents": "Effect of porcine calcitonin on the metabolism of calcium and cyclic AMP in rat skeletal tissue in vivo. Infusion of 50 mU/100 g body wt of calcitonin induced a rapid and marked increase of cyclic AMP in calvaria as well as in plasma of thyroparathyroidectomized rats. These changes preceded the decrease in plasma calcium concentration seen after hormone administration. The possible relationship of this stimulation of cyclic AMP accumulation to the hypocalcemic effect of calcitonin was examined under several experimental settings. It was found that a dose of calcitonin sufficient to cause a significant decrease of plasma calcium failed to produce any detectable accumulation cyclic AMP in calvaria, but when high doses of calcitonin were given, there was an apparent correlation between the integrated change of cyclic AMP metabolism and the duration and magnitude of hypocalcemia. Experiments employing the ophylline and imidazole, which alter cyclic AMP metabolism, led to an apparent dissociation between the hypocalcemic effect of calcitonin and its stimulation of cyclic AMP accumulation in bone."} {"id": "PMID:170064", "title": "The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat.", "content": "The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.", "contents": "The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat. The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant."} {"id": "PMID:170065", "title": "On the mechanism of prolactin and estrogen action in 7,12 dimethylbenz(A)anthracene-induced mammary carcinoma in the rat. II. In vivo tumor responses and estrogen receptor.", "content": "In order to test the in vivo effect of prolactin on estrogen receptor (ER) binding capacity in tumors induced by 7,12 dimethylbenz(a)anthrancene (DMBA-tumor), growth of the tumors from changes in prolactin and estrogen levels was compared retrospectively with cytoplasmic ER levels. It was demonstrated that some tumors required prolactin, some needed prolactin-estrogen during their growth period anda small number were not influenced by hormonal milieu. ER was present in hormonally dependent tumors but was low or absent in hormonaly-independent tumors. Deletion of hormones by endocrine ablation in the host rat resulted in tumor regression loss of ER. Replenishment of ER and subsequent tumor growth were accomplished by injection of prolactin or prolactin-estrogen in endocrine ablated rats but were not achieved in rats bearing tumors exposed to prolactin-nafoxidine. Our results demonstrate that both estrogen and prolactin were essential for growth of hormonally dependent DMBA-tumors. Tumor growth was also prevented when cytoplasmic ER was not replenished , indicating that ER may be an indispensable prerequisite for growth. Prolactin, independently of or cooperatively with estrogen, stimulated ER binding capacity. These results support the hypothesis that there may exist a prolactin regulatory mechanism of estrogen action at the tumor site. The interactions of estrogen and prolactin in situ in modulating hormonal receptor binding capacities may contribute to the overall stimulatory effect of these two hormones on DMBA-tumors.", "contents": "On the mechanism of prolactin and estrogen action in 7,12 dimethylbenz(A)anthracene-induced mammary carcinoma in the rat. II. In vivo tumor responses and estrogen receptor. In order to test the in vivo effect of prolactin on estrogen receptor (ER) binding capacity in tumors induced by 7,12 dimethylbenz(a)anthrancene (DMBA-tumor), growth of the tumors from changes in prolactin and estrogen levels was compared retrospectively with cytoplasmic ER levels. It was demonstrated that some tumors required prolactin, some needed prolactin-estrogen during their growth period anda small number were not influenced by hormonal milieu. ER was present in hormonally dependent tumors but was low or absent in hormonaly-independent tumors. Deletion of hormones by endocrine ablation in the host rat resulted in tumor regression loss of ER. Replenishment of ER and subsequent tumor growth were accomplished by injection of prolactin or prolactin-estrogen in endocrine ablated rats but were not achieved in rats bearing tumors exposed to prolactin-nafoxidine. Our results demonstrate that both estrogen and prolactin were essential for growth of hormonally dependent DMBA-tumors. Tumor growth was also prevented when cytoplasmic ER was not replenished , indicating that ER may be an indispensable prerequisite for growth. Prolactin, independently of or cooperatively with estrogen, stimulated ER binding capacity. These results support the hypothesis that there may exist a prolactin regulatory mechanism of estrogen action at the tumor site. The interactions of estrogen and prolactin in situ in modulating hormonal receptor binding capacities may contribute to the overall stimulatory effect of these two hormones on DMBA-tumors."} {"id": "PMID:170066", "title": "The effects of exogenous gonadotropins on ovarian adenylate cyclase activity.", "content": "Adenylate cyclase was assayed in pellets prepared by centrifuging for 10 min at 600 x g homogenates of ovaries of immature rats treated with PMS and hCG. Activity was detected in the absence of any stimulatory agents and increased markedly in the presence of fluoride. Dose-dependent activity occurred in vitro in response to LH ranging from 0.2 to 10 mug/ml of incubate but not at higher concentrations. Marked changes in adenylate cyclase activities were observed with preparations from ovaries excised at various times after gonadotropin treatment. These changes, measured as the response to both fluoride and LH were observed to occur in four main stages. An initial decrease occurred 1/2 to 1 day after administration of hCG. Activity then increased and remained significantly elevated from day 3 to 7. A second but more dramatic rise was observed on day 8 and this enhanced level of activity remained elevated until day 13. A decreased level of activity occurred on day 15. Unstimulated activity remained low for the 16 day period studied although significant rises were observed on day 3 and days 8 to 15 after the administration of hCG. We have suggested that these changes in the adenylate cyclase activity modulate the level of cyclic AMP in the luteal cells and thereby induce changes in the activity of enzymes involved in progestin biosynthesis.", "contents": "The effects of exogenous gonadotropins on ovarian adenylate cyclase activity. Adenylate cyclase was assayed in pellets prepared by centrifuging for 10 min at 600 x g homogenates of ovaries of immature rats treated with PMS and hCG. Activity was detected in the absence of any stimulatory agents and increased markedly in the presence of fluoride. Dose-dependent activity occurred in vitro in response to LH ranging from 0.2 to 10 mug/ml of incubate but not at higher concentrations. Marked changes in adenylate cyclase activities were observed with preparations from ovaries excised at various times after gonadotropin treatment. These changes, measured as the response to both fluoride and LH were observed to occur in four main stages. An initial decrease occurred 1/2 to 1 day after administration of hCG. Activity then increased and remained significantly elevated from day 3 to 7. A second but more dramatic rise was observed on day 8 and this enhanced level of activity remained elevated until day 13. A decreased level of activity occurred on day 15. Unstimulated activity remained low for the 16 day period studied although significant rises were observed on day 3 and days 8 to 15 after the administration of hCG. We have suggested that these changes in the adenylate cyclase activity modulate the level of cyclic AMP in the luteal cells and thereby induce changes in the activity of enzymes involved in progestin biosynthesis."} {"id": "PMID:170067", "title": "Glucocorticoid and mineralocorticoid receptors in gut mucosa.", "content": "Both glucocorticoid and mineralocorticoid hormones are known to be involved in the physiology and pathophysiology of the gastrointestinal tract. Studies on the mechanism of action of steroid hormones indicate an initial obligatory step of binding to stereospecific receptor proteins in the cytoplasm of target tissue cells. Mucosal cells from the gastrointestinal tract of adrenalectomized, gonadectomized rats contain cytoplasmic glucocorticoid receptors which bind tritiated dexamethasone with an affinity (Kdiss4C) of approximately 10(-8)M. The concentration of glucocorticoid receptors per unit cytoplasmic protein is in order duodenum greater than jejunum greater than ileum=stomach greater than colon, and their affinity for steroid hormones is in order dexamethasone greater than corticosterone greater than deoxycorticosterone=aldosterone. No glucocorticoid receptors could be demonstrated in esophageal mucosal cells. Binding sites for tritiated aldosterone, with affinity characteristics appropriate for physiological mineralocorticoid receptors, were demonstrated in duodenum, jejunum, ileum and colon. No similar sites could be shown in the mucosa of the gastric antrum.", "contents": "Glucocorticoid and mineralocorticoid receptors in gut mucosa. Both glucocorticoid and mineralocorticoid hormones are known to be involved in the physiology and pathophysiology of the gastrointestinal tract. Studies on the mechanism of action of steroid hormones indicate an initial obligatory step of binding to stereospecific receptor proteins in the cytoplasm of target tissue cells. Mucosal cells from the gastrointestinal tract of adrenalectomized, gonadectomized rats contain cytoplasmic glucocorticoid receptors which bind tritiated dexamethasone with an affinity (Kdiss4C) of approximately 10(-8)M. The concentration of glucocorticoid receptors per unit cytoplasmic protein is in order duodenum greater than jejunum greater than ileum=stomach greater than colon, and their affinity for steroid hormones is in order dexamethasone greater than corticosterone greater than deoxycorticosterone=aldosterone. No glucocorticoid receptors could be demonstrated in esophageal mucosal cells. Binding sites for tritiated aldosterone, with affinity characteristics appropriate for physiological mineralocorticoid receptors, were demonstrated in duodenum, jejunum, ileum and colon. No similar sites could be shown in the mucosa of the gastric antrum."} {"id": "PMID:170068", "title": "Increased rate of response of the pituitary-adrenal system in rats adapted to chronic stress.", "content": "The response and adaptation of the pituitary-adrenal system to chronic stresses was investigated. These included individual caging, confinement, and exposure to cold for varying periods of time. Studies were carried out demonstrating that during the period of adaptation when plasma corticosterone concentrations returned toward their prestress level despite continued exposure to the stressor, the animals responded to additional stimuli of ether for 1 min, a saline injection, or release from confinement with a faster increase (within 2.5 min) in plasma corticosterone than controls (10 min). This increased responsiveness was not limited to the adrenal since plasma ACTH showed a greater increase 2.5 min after ether in animals confined for 40 min than in nonconfined rats. It is concluded that during adaptation to a chronic stress the pituitary-adrenal system is not inhibited by the circulating steroid level but is actually hypersensitive to additional stimuli. Thus, chronic stress may cause an increased drive to the ACTH-secreting mechanism which compensates or overrides the cortical feedback.", "contents": "Increased rate of response of the pituitary-adrenal system in rats adapted to chronic stress. The response and adaptation of the pituitary-adrenal system to chronic stresses was investigated. These included individual caging, confinement, and exposure to cold for varying periods of time. Studies were carried out demonstrating that during the period of adaptation when plasma corticosterone concentrations returned toward their prestress level despite continued exposure to the stressor, the animals responded to additional stimuli of ether for 1 min, a saline injection, or release from confinement with a faster increase (within 2.5 min) in plasma corticosterone than controls (10 min). This increased responsiveness was not limited to the adrenal since plasma ACTH showed a greater increase 2.5 min after ether in animals confined for 40 min than in nonconfined rats. It is concluded that during adaptation to a chronic stress the pituitary-adrenal system is not inhibited by the circulating steroid level but is actually hypersensitive to additional stimuli. Thus, chronic stress may cause an increased drive to the ACTH-secreting mechanism which compensates or overrides the cortical feedback."} {"id": "PMID:170069", "title": "The effect of fasting on tissue cyclic cAMP and plasma glucagon in the obese hyperglycemic mouse.", "content": "The effect of 48 h of fasting in C57B1/6J-ob/ob and +/+ mice on body weight (BW), blood glucose (BG), serum immunreactive insulin (IRI), plasma immunoreactive glucagon (IRG) and on tissue levels of cyclic adenosine monophosphate (cAMP) were studied. Both groups of mice lost weight and demonstrated a decrease in BG and IRI with fasting. However, the BG and IRI of the ob/ob animals were initially highter and remained higher than those of the 2% of their initial weight while the +/+ lost 14 %. The +/+ mice exhibited an increase in cAMP levels in skeletal muscle, fat and liver with fasting, while the ob/ob mice had increased levels of cAMP in fat, but not in muscle. They also had a paradoxical decrease in liver cAMP levels with fasting, and associated with this was the lack of stimulation of glycogenolysis. Glycogenolysis was significant in the livers of fasted +/+ mice. The plasma IRG levels of the fed ob/ob mice were significantly higher (1.8) times) than those of the fed +/+ mice. Islet cAMP levels were decreased with fasting in ob/ob mice. However, the levels were significantly higher in 48-h faster ob/ob mice compared to the fasted +/+ group. The apparent paradoxical response to fasting observed in the livers of the ob/ob mice remains unexplained.", "contents": "The effect of fasting on tissue cyclic cAMP and plasma glucagon in the obese hyperglycemic mouse. The effect of 48 h of fasting in C57B1/6J-ob/ob and +/+ mice on body weight (BW), blood glucose (BG), serum immunreactive insulin (IRI), plasma immunoreactive glucagon (IRG) and on tissue levels of cyclic adenosine monophosphate (cAMP) were studied. Both groups of mice lost weight and demonstrated a decrease in BG and IRI with fasting. However, the BG and IRI of the ob/ob animals were initially highter and remained higher than those of the 2% of their initial weight while the +/+ lost 14 %. The +/+ mice exhibited an increase in cAMP levels in skeletal muscle, fat and liver with fasting, while the ob/ob mice had increased levels of cAMP in fat, but not in muscle. They also had a paradoxical decrease in liver cAMP levels with fasting, and associated with this was the lack of stimulation of glycogenolysis. Glycogenolysis was significant in the livers of fasted +/+ mice. The plasma IRG levels of the fed ob/ob mice were significantly higher (1.8) times) than those of the fed +/+ mice. Islet cAMP levels were decreased with fasting in ob/ob mice. However, the levels were significantly higher in 48-h faster ob/ob mice compared to the fasted +/+ group. The apparent paradoxical response to fasting observed in the livers of the ob/ob mice remains unexplained."} {"id": "PMID:170070", "title": "Anterior pituitary vasodilation after hemorrhage in the dog.", "content": "A miniature thermoelectric probe was used to record continuously tissue blood flow in the anterior pituitary gland of anesthetized dogs. The output of the flow probe is linear in the range of tissue blood flow encountered in the pituitary. Probe placement required minimal tissue trauma, and zero blood flow was recorded at the end of each experiment. Little or no change in flow followed hemorrhage of 10 ml/kg body weight. However, hemorrhages of 20 or 30 ml/kg were followed by a biphasic deviation from control level, with an initial transient decrease in flow, followed by recovery to control at about 19 min and a rise above control to 90% of maximum at about 32 min. Hypothalamohypophysial vascular resistance was found to decrease significantly following hemorrhages of 20 or 30 ml/kg, and this was shown to be independent of resistance changes in the femoral vascular bed. It is concluded that anterior pituitary blood flow is well maintained following moderate hemorrhage as a result of intrinsic vasodilation in the hypothalamo-hypophysial vascular bed.", "contents": "Anterior pituitary vasodilation after hemorrhage in the dog. A miniature thermoelectric probe was used to record continuously tissue blood flow in the anterior pituitary gland of anesthetized dogs. The output of the flow probe is linear in the range of tissue blood flow encountered in the pituitary. Probe placement required minimal tissue trauma, and zero blood flow was recorded at the end of each experiment. Little or no change in flow followed hemorrhage of 10 ml/kg body weight. However, hemorrhages of 20 or 30 ml/kg were followed by a biphasic deviation from control level, with an initial transient decrease in flow, followed by recovery to control at about 19 min and a rise above control to 90% of maximum at about 32 min. Hypothalamohypophysial vascular resistance was found to decrease significantly following hemorrhages of 20 or 30 ml/kg, and this was shown to be independent of resistance changes in the femoral vascular bed. It is concluded that anterior pituitary blood flow is well maintained following moderate hemorrhage as a result of intrinsic vasodilation in the hypothalamo-hypophysial vascular bed."} {"id": "PMID:170071", "title": "Specific prolactin binding sites in the prostate and testis of rats.", "content": "Specific binding sites for prolactin have been detected in membrane preparations from the testis, epididymis, seminal vesicles and prostate of male rats. The binding was time and temperature dependent. In prostatic tissue the binding of prolactin was a saturable process with an association constant (Ka) of 3 X 10(9) M-1 and a binding capacity of 125 femtomoles per mg of protein. The binding of prolactin to the prostate was inhibited only by lactogenic hormones. In the testis the low binding of prolactin increased slightly from 20 to 70 days of age. On the other hand, in the prostate the highest specific binding was found in membrane preparation from 20-day-old rats while 270-day-old rats had only 10% as much specific binding. The administration of estrogen also lowered prolactin binding to prostatic membranes. Castration caused an even greater decrease in the binding of [125I] iodo PRL in the prostate whereas in the liver this procedure resulted in a major increase in the binding of labeled prolactin.", "contents": "Specific prolactin binding sites in the prostate and testis of rats. Specific binding sites for prolactin have been detected in membrane preparations from the testis, epididymis, seminal vesicles and prostate of male rats. The binding was time and temperature dependent. In prostatic tissue the binding of prolactin was a saturable process with an association constant (Ka) of 3 X 10(9) M-1 and a binding capacity of 125 femtomoles per mg of protein. The binding of prolactin to the prostate was inhibited only by lactogenic hormones. In the testis the low binding of prolactin increased slightly from 20 to 70 days of age. On the other hand, in the prostate the highest specific binding was found in membrane preparation from 20-day-old rats while 270-day-old rats had only 10% as much specific binding. The administration of estrogen also lowered prolactin binding to prostatic membranes. Castration caused an even greater decrease in the binding of [125I] iodo PRL in the prostate whereas in the liver this procedure resulted in a major increase in the binding of labeled prolactin."} {"id": "PMID:170072", "title": "The effect of hypophysectomy on the function of the insulin-sensitive central nervous system glucoregulator receptor.", "content": "Hypophysectomized and healthy control rats were studied to investigate the mechanism of action of the insulin-sensitive glucoregulator receptor of the central nervous system (CNS). Glucagon-free insulin (500 muU) was injected into the carotid artery, and the peripheral blood glucose was monitored. An immediate significant fall in the blood sugar was observed in intact as well as in hypophysectomized rats. To control these experiments buffer was injected into the carotid artery, or 500 muU insulin was given through the jugular vein of intact and hypophysectomized animals. The systemic blood sugar level remained unchanged for 10-15 min in the control experiments. The results indicate that the function of this insulin-sensitive glucoregulator CNS receptor is not impaired in the hypophysectomized state. The initial phase of its effect, the sudden decrease of the blood sugar level, appears to be independent of pituitary hormone secretion.", "contents": "The effect of hypophysectomy on the function of the insulin-sensitive central nervous system glucoregulator receptor. Hypophysectomized and healthy control rats were studied to investigate the mechanism of action of the insulin-sensitive glucoregulator receptor of the central nervous system (CNS). Glucagon-free insulin (500 muU) was injected into the carotid artery, and the peripheral blood glucose was monitored. An immediate significant fall in the blood sugar was observed in intact as well as in hypophysectomized rats. To control these experiments buffer was injected into the carotid artery, or 500 muU insulin was given through the jugular vein of intact and hypophysectomized animals. The systemic blood sugar level remained unchanged for 10-15 min in the control experiments. The results indicate that the function of this insulin-sensitive glucoregulator CNS receptor is not impaired in the hypophysectomized state. The initial phase of its effect, the sudden decrease of the blood sugar level, appears to be independent of pituitary hormone secretion."} {"id": "PMID:170073", "title": "Influence of thyroid hormone on glycogen metabolism in rat liver.", "content": "The livers removed from thyroidectomized and L-T4 supplemented rats were rapidly frozen by Freon-12 chilled with liquid nitrogen, and concentrations of metabolites which affect glycogen synthetase and phosphorylase were determined. Serum and liver glycose levels were not changed in any thyroid functioning. But liver G6P and ATP were increased by thyroidectomy and decreased by L-T4 supplement, while cAMP was increased by the hormone supplement. The \"enzyme activity\" ratio of glycogen synthetase a to phosphorylase a was increased by thyroidectomy and decreased by L-T4 supplement. The most intimate correlation was observed between the \"enzyme activity\" ratio and the ratio of the \"energy charge\" ratio of cAMP among other indices calculated from changes in the metabolite concentrations in the various thyroid functioning. The change in the substrate levels brought about by thyroidectomy and L-T4 supplement appeared to modulate both the enzyme activities which in turn regulate the glycogen metabolism.", "contents": "Influence of thyroid hormone on glycogen metabolism in rat liver. The livers removed from thyroidectomized and L-T4 supplemented rats were rapidly frozen by Freon-12 chilled with liquid nitrogen, and concentrations of metabolites which affect glycogen synthetase and phosphorylase were determined. Serum and liver glycose levels were not changed in any thyroid functioning. But liver G6P and ATP were increased by thyroidectomy and decreased by L-T4 supplement, while cAMP was increased by the hormone supplement. The \"enzyme activity\" ratio of glycogen synthetase a to phosphorylase a was increased by thyroidectomy and decreased by L-T4 supplement. The most intimate correlation was observed between the \"enzyme activity\" ratio and the ratio of the \"energy charge\" ratio of cAMP among other indices calculated from changes in the metabolite concentrations in the various thyroid functioning. The change in the substrate levels brought about by thyroidectomy and L-T4 supplement appeared to modulate both the enzyme activities which in turn regulate the glycogen metabolism."} {"id": "PMID:170074", "title": "Determination of the association constants and maximum binding capacities between estradiol and cytosol of the uterus by the least-squares analysis of the Scatchard plot.", "content": "The association constants and the binding capacities of association of small molecules with macromolecules have been determined by the tangent analysis, the graphical analysis, and the computer data analysis, by trial and convergence of the Scatchard plot. The analytical method for the calculation of the binding parameters based on the Scatchard plot was derived and the optimum values of the binding parameters were obtained by the least squares calculation based on the analytical method. The errors by the analytical method were smaller than those by the graphical method in the equilibrium system between 3H-estradiol and some cytosols of uterus.", "contents": "Determination of the association constants and maximum binding capacities between estradiol and cytosol of the uterus by the least-squares analysis of the Scatchard plot. The association constants and the binding capacities of association of small molecules with macromolecules have been determined by the tangent analysis, the graphical analysis, and the computer data analysis, by trial and convergence of the Scatchard plot. The analytical method for the calculation of the binding parameters based on the Scatchard plot was derived and the optimum values of the binding parameters were obtained by the least squares calculation based on the analytical method. The errors by the analytical method were smaller than those by the graphical method in the equilibrium system between 3H-estradiol and some cytosols of uterus."} {"id": "PMID:170075", "title": "Respiratory effects in toluene diisocyanate manufacture: a multidisciplinary approach.", "content": "A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become \"clinically sensitized\" to TDI and have been removed from regular TDI exposure. To date, the total number of workers who report the presence of recurring respiratory symptoms has not increased in comparison with the pre-exposure survey. Pulmonary function data after one full year of TDI exposure are not yet available. Pre- and post-shift ventilatory function studies do not indicate significant differences between the exposed and control groups. Selected individuals had carefully controlled inhalation challenge tests to monitored concentrations of TDI vapor under laboratory conditions. In workers suspected of having become \"sensitized\", immediate and/or late air flow obstruction was demonstrated and could be related to dose of inhaled TDI.", "contents": "Respiratory effects in toluene diisocyanate manufacture: a multidisciplinary approach. A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become \"clinically sensitized\" to TDI and have been removed from regular TDI exposure. To date, the total number of workers who report the presence of recurring respiratory symptoms has not increased in comparison with the pre-exposure survey. Pulmonary function data after one full year of TDI exposure are not yet available. Pre- and post-shift ventilatory function studies do not indicate significant differences between the exposed and control groups. Selected individuals had carefully controlled inhalation challenge tests to monitored concentrations of TDI vapor under laboratory conditions. In workers suspected of having become \"sensitized\", immediate and/or late air flow obstruction was demonstrated and could be related to dose of inhaled TDI."} {"id": "PMID:170076", "title": "Nervous system degeneration produced by acrylamide monomer.", "content": "Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.", "contents": "Nervous system degeneration produced by acrylamide monomer. Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration."} {"id": "PMID:170077", "title": "Physiological and toxicological aspects of smoke produced during the combustion of polymeric materials.", "content": "Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered.", "contents": "Physiological and toxicological aspects of smoke produced during the combustion of polymeric materials. Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered."} {"id": "PMID:170078", "title": "Epidemiology of toluene diisocyanate (TDI)-induced respiratory disease.", "content": "This paper describes our experience with the respiratory effects of TDI. Five respiratory reactions attributable to TDI are described with supporting evidence. The reactions are sensitization, irritation from overexposure, acute loss of ventilatory capacity, accelerated loss of pulmonary function and induction of a general asthmatic state. Evidence is presented that suggests a safe exposure level.", "contents": "Epidemiology of toluene diisocyanate (TDI)-induced respiratory disease. This paper describes our experience with the respiratory effects of TDI. Five respiratory reactions attributable to TDI are described with supporting evidence. The reactions are sensitization, irritation from overexposure, acute loss of ventilatory capacity, accelerated loss of pulmonary function and induction of a general asthmatic state. Evidence is presented that suggests a safe exposure level."} {"id": "PMID:170080", "title": "Enzymatic changes in lung tissue of asbestotic guinea pigs.", "content": "The changes in the activities of some mitochondrial and soluble enzymes in the lungs of guinea pig, caused by three varieties of asbestos dust 120 days after intratracheal injection, were studied. Marked increase was observed in mitochondrial cytochrome oxidase, diaphorase and malic dehydrogenase. Among the soluble enzymes, lactic dehydrogenase showed the maximum variation.", "contents": "Enzymatic changes in lung tissue of asbestotic guinea pigs. The changes in the activities of some mitochondrial and soluble enzymes in the lungs of guinea pig, caused by three varieties of asbestos dust 120 days after intratracheal injection, were studied. Marked increase was observed in mitochondrial cytochrome oxidase, diaphorase and malic dehydrogenase. Among the soluble enzymes, lactic dehydrogenase showed the maximum variation."} {"id": "PMID:170081", "title": "On the activity and regulation of anaplerotic and gluconeogenetic enzymes during the growth process of baker's yeast. The biphasic growth.", "content": "The anaplerotic and gluconeogenetic metabolism of baker's yeast was studied at the enzymatic level during glucose-ethanol diauxic growth in the presence and absence of aspartate. Of the two possible anaplerotic systems, only the pyruvate carboxylase by-pass was present during the whole growth process. The second system, the glyoxylate by-pass (isocitrate lyase as the indicator), like the specific enzymes of the gluconeogenetic metabolism, phosphoenolpyruvate carboxykinase and hexosediphosphatase began to appear only after the glucose had been consumed. The addition of glucose during the growth phase based on ethanol effected a rapid disappearance of phosphoenolpyruvate carboxykinase and hexosediphosphatase activities. The activity of pyruvate carboxylase decreased when the growth medium was supplied with asparate. The presence of aspartate had no effect on the activities of the other enzymes studied.", "contents": "On the activity and regulation of anaplerotic and gluconeogenetic enzymes during the growth process of baker's yeast. The biphasic growth. The anaplerotic and gluconeogenetic metabolism of baker's yeast was studied at the enzymatic level during glucose-ethanol diauxic growth in the presence and absence of aspartate. Of the two possible anaplerotic systems, only the pyruvate carboxylase by-pass was present during the whole growth process. The second system, the glyoxylate by-pass (isocitrate lyase as the indicator), like the specific enzymes of the gluconeogenetic metabolism, phosphoenolpyruvate carboxykinase and hexosediphosphatase began to appear only after the glucose had been consumed. The addition of glucose during the growth phase based on ethanol effected a rapid disappearance of phosphoenolpyruvate carboxykinase and hexosediphosphatase activities. The activity of pyruvate carboxylase decreased when the growth medium was supplied with asparate. The presence of aspartate had no effect on the activities of the other enzymes studied."} {"id": "PMID:170082", "title": "Dynamic control on the rate of the reduction of the b type cytochromes in submitochondrial particles.", "content": "1. In the presence of antimycin and KCN the reduction of cytochrome b in phosphorylating submitochondrial particles followed a biphasic first-order kinetics. The transition from the first, rapid phase to the second, slow phase occurred while the reduction of chtochromes c + c1 and a through or around the antimycin block was still linear with time. Thus, the phase transition was due to a fall-off in the rate of cytochrome b reduction. 2. The biphasic reduction of cytochrome b was observed over a wide temperature range (0--30 degrees C), with succinate of NADH as electron donors and with phosphorylating particles or coupled rat-heart mitochondria. With rat-heart mitochondria the same biphasic reduction was observed in the presence of either carbonyl cyanide p-trifluoromethoxyphenylhydrazone or oligomycin. 3. In both the rapid and the slow phases, the rate of reduction of cytochrome b-561 was equal to that of b-565. Thus both cytochromes b-561 and b-565 were affected by the mechanism which determined the reduction-rate. Furthermore, each of these cytochromes could be reduced individually with rate constants typical of the slow phase. 4. The proportion of rapidly reduced to slowly reduced cytochrome b was independent of the degree of its reducibility and could be controlled by teh experimental conditions. When antimycin was used as the only inhibitor, 96% of the b-type cytochromes were reduced in the rapid phase. If the c and a-type cytochromes were first reduced by ascorbate and tetramethyl-p-phenylenediamine in the presence of KCN and antimycin, all the b-type cytochromes were fully reduced at the slow-rate. 5. With succinate, the rate of the rapid phase depended on the activation level of the succinic-dehydrogenase. The rate constant of the second phase was unaffected by the succinic dehydrogenase activity, if the preparation was more than 20% active. Furthermore, the rate constant of the slow reduction was the same with succinate, NADH, or even with durohydroquinone (which reacted directly with cytochromes b). 6. It is suggested that cytochrome b can exist in two forms: kinetically active or sluggish. The active form is rapidly reduced by the endogenous quinone (QH2) or durohydroquinone. The rate of the reduction of the active form by succinate or NADH is probably determined by the rate of the reduction of Q by the dehydrogenases. The second form of cytochrome b is characterized by its sluggish reduction by QH2 or durohydroquinone. 7. It is proposed that the transformation from the active to the sluggish form is induced by the reduction of a controlling group, named Y, located on the oxygen side of the antimycin inhibition site. When Y is oxidized, cytochrome b is in its active form, and when Y is reduced, cytochrome b is in its sluggish form. The nature of this kinetic control and a comparison with the mechanism controlling the reducibility of cytochrome b are discussed.", "contents": "Dynamic control on the rate of the reduction of the b type cytochromes in submitochondrial particles. 1. In the presence of antimycin and KCN the reduction of cytochrome b in phosphorylating submitochondrial particles followed a biphasic first-order kinetics. The transition from the first, rapid phase to the second, slow phase occurred while the reduction of chtochromes c + c1 and a through or around the antimycin block was still linear with time. Thus, the phase transition was due to a fall-off in the rate of cytochrome b reduction. 2. The biphasic reduction of cytochrome b was observed over a wide temperature range (0--30 degrees C), with succinate of NADH as electron donors and with phosphorylating particles or coupled rat-heart mitochondria. With rat-heart mitochondria the same biphasic reduction was observed in the presence of either carbonyl cyanide p-trifluoromethoxyphenylhydrazone or oligomycin. 3. In both the rapid and the slow phases, the rate of reduction of cytochrome b-561 was equal to that of b-565. Thus both cytochromes b-561 and b-565 were affected by the mechanism which determined the reduction-rate. Furthermore, each of these cytochromes could be reduced individually with rate constants typical of the slow phase. 4. The proportion of rapidly reduced to slowly reduced cytochrome b was independent of the degree of its reducibility and could be controlled by teh experimental conditions. When antimycin was used as the only inhibitor, 96% of the b-type cytochromes were reduced in the rapid phase. If the c and a-type cytochromes were first reduced by ascorbate and tetramethyl-p-phenylenediamine in the presence of KCN and antimycin, all the b-type cytochromes were fully reduced at the slow-rate. 5. With succinate, the rate of the rapid phase depended on the activation level of the succinic-dehydrogenase. The rate constant of the second phase was unaffected by the succinic dehydrogenase activity, if the preparation was more than 20% active. Furthermore, the rate constant of the slow reduction was the same with succinate, NADH, or even with durohydroquinone (which reacted directly with cytochromes b). 6. It is suggested that cytochrome b can exist in two forms: kinetically active or sluggish. The active form is rapidly reduced by the endogenous quinone (QH2) or durohydroquinone. The rate of the reduction of the active form by succinate or NADH is probably determined by the rate of the reduction of Q by the dehydrogenases. The second form of cytochrome b is characterized by its sluggish reduction by QH2 or durohydroquinone. 7. It is proposed that the transformation from the active to the sluggish form is induced by the reduction of a controlling group, named Y, located on the oxygen side of the antimycin inhibition site. When Y is oxidized, cytochrome b is in its active form, and when Y is reduced, cytochrome b is in its sluggish form. The nature of this kinetic control and a comparison with the mechanism controlling the reducibility of cytochrome b are discussed."} {"id": "PMID:170083", "title": "tRNA nucleotidyltransferase-catalyzed incorporation of CMP and AMP into RNA-bacteriophage genome fragments.", "content": "Fragments of bacteriophage RNAs R17, MS2 and Qbeta obtained by incubation with commercial snake venom phosphodiesterase become substrates of the Escherichia coli tRNA nucleotidyltransferase. The transferase adds back CMP and AMP in conditions in which it remains highly specific of CCA-deprived tRNAs. The results suggest that the fragment from the 3' end of the viral genome and/or possibly one or more internal fragment(s) are recognized by the transferase. These observations might indicate that bacteriophage RNAs contain certain features probably present in all tRNAs and which are recognized by the transferase.", "contents": "tRNA nucleotidyltransferase-catalyzed incorporation of CMP and AMP into RNA-bacteriophage genome fragments. Fragments of bacteriophage RNAs R17, MS2 and Qbeta obtained by incubation with commercial snake venom phosphodiesterase become substrates of the Escherichia coli tRNA nucleotidyltransferase. The transferase adds back CMP and AMP in conditions in which it remains highly specific of CCA-deprived tRNAs. The results suggest that the fragment from the 3' end of the viral genome and/or possibly one or more internal fragment(s) are recognized by the transferase. These observations might indicate that bacteriophage RNAs contain certain features probably present in all tRNAs and which are recognized by the transferase."} {"id": "PMID:170084", "title": "Paramagnetic and fluorescent probes attached to \"buried\" sulfhydryl groups in human carbonic anhydrases. Application to inhibitor binding, denaturation and refolding.", "content": "1. The single -SH groups in the human carbonic anhydrases B and C have been modified under denaturing conditions. The modified enzymes recover catalytic activity after dilution of the denaturing medium with buffer. By this method a spin label and a fluorescent probe were specifically introduced into the molecules. 2. The modified and reactivated enzymes have similar kinetic properties, inhibitor-binding constants, circular dichroism spectra, and stabilities towards guanidine hydrochloride as the native enzymes. However, the esterase activity of the modified C enzyme is reduced to about 50%. 3. The spectra associated with the probes are insensitive to inhibitor binding in case of the B enzyme, whereas changes of electron paramagnetic resonance spectrum and fluorescence intensity respectively, were observed for the probe-containing C enzymes. The cysteines are located in different parts of the tertiary structures of the homologous B and C enzymes, and these observations suggest that small conformational changes accompanying inhibitor binding are localized to regions of the molecules near the active-site cavity. 4. During denaturation of the spin-labeled B enzyme in 1.7 M guanidine hydrochloride a transient mobilization of the probe occurs, but the mobility is ultimately reduced to a low level. This observation supports previous evidence that denaturation under these conditions, in or near the transition region, mainly yields incorrectly folded molecules rather than stable intermediates between native and fully denatured molecules. 5. During refolding of fully denatured, spin-labeled B and C enzymes the mobility of the probe is drastically reduced within less than 0.1 s after dilution. This would reflect a very short lifetime of the randomly coiled state under these conditions.", "contents": "Paramagnetic and fluorescent probes attached to \"buried\" sulfhydryl groups in human carbonic anhydrases. Application to inhibitor binding, denaturation and refolding. 1. The single -SH groups in the human carbonic anhydrases B and C have been modified under denaturing conditions. The modified enzymes recover catalytic activity after dilution of the denaturing medium with buffer. By this method a spin label and a fluorescent probe were specifically introduced into the molecules. 2. The modified and reactivated enzymes have similar kinetic properties, inhibitor-binding constants, circular dichroism spectra, and stabilities towards guanidine hydrochloride as the native enzymes. However, the esterase activity of the modified C enzyme is reduced to about 50%. 3. The spectra associated with the probes are insensitive to inhibitor binding in case of the B enzyme, whereas changes of electron paramagnetic resonance spectrum and fluorescence intensity respectively, were observed for the probe-containing C enzymes. The cysteines are located in different parts of the tertiary structures of the homologous B and C enzymes, and these observations suggest that small conformational changes accompanying inhibitor binding are localized to regions of the molecules near the active-site cavity. 4. During denaturation of the spin-labeled B enzyme in 1.7 M guanidine hydrochloride a transient mobilization of the probe occurs, but the mobility is ultimately reduced to a low level. This observation supports previous evidence that denaturation under these conditions, in or near the transition region, mainly yields incorrectly folded molecules rather than stable intermediates between native and fully denatured molecules. 5. During refolding of fully denatured, spin-labeled B and C enzymes the mobility of the probe is drastically reduced within less than 0.1 s after dilution. This would reflect a very short lifetime of the randomly coiled state under these conditions."} {"id": "PMID:170085", "title": "An affinity-column procedure using poly(L-proline) for the purification of prolyl hydroxylase. Purification of the enzyme from chick embryos.", "content": "An affinity column procedure is reported for purifying prolyl hydroxylase. The procedure is based on the affinity of the enzyme for its competitive polypeptide inhibitor, and involves affinity chromatography in a column containing poly(L-proline) of molecular weight 30000 linked to agarose, and the elution of the enzyme from the column with poly(L-proline) of molecular weight 5700. The enzyme is finally separated from this polyproline by gel filtration. The procedure was employed for purifying prolyl hydroxylase from an ammonium sulphate fraction of chick embryo extract. The recovery of enzyme activity varied in ten enzyme preparations from 50 to 82%, and the purified preparations synthesized from 59.3 to 91.5 mumol hydroxyproline per mg enzyme per h at 37 degrees C with a saturating concentration of (Pro-Pro-Gly)5 as substrate. The enzyme was pure when examined by polyacrylamide gel electrophoresis as a native protein or in the presence of sodium dodecyl sulphate, and the amino acid composition of the enzyme agreed with that reported previously with only minor exceptions. The molecular weight of the enzyme measured by equilibrium in an analytical ultracentrifuge was 240000, indicating that the enzyme had been isolated in the tetramer form.", "contents": "An affinity-column procedure using poly(L-proline) for the purification of prolyl hydroxylase. Purification of the enzyme from chick embryos. An affinity column procedure is reported for purifying prolyl hydroxylase. The procedure is based on the affinity of the enzyme for its competitive polypeptide inhibitor, and involves affinity chromatography in a column containing poly(L-proline) of molecular weight 30000 linked to agarose, and the elution of the enzyme from the column with poly(L-proline) of molecular weight 5700. The enzyme is finally separated from this polyproline by gel filtration. The procedure was employed for purifying prolyl hydroxylase from an ammonium sulphate fraction of chick embryo extract. The recovery of enzyme activity varied in ten enzyme preparations from 50 to 82%, and the purified preparations synthesized from 59.3 to 91.5 mumol hydroxyproline per mg enzyme per h at 37 degrees C with a saturating concentration of (Pro-Pro-Gly)5 as substrate. The enzyme was pure when examined by polyacrylamide gel electrophoresis as a native protein or in the presence of sodium dodecyl sulphate, and the amino acid composition of the enzyme agreed with that reported previously with only minor exceptions. The molecular weight of the enzyme measured by equilibrium in an analytical ultracentrifuge was 240000, indicating that the enzyme had been isolated in the tetramer form."} {"id": "PMID:170086", "title": "Biospecific affinity chromatography in aqueous-organic cosolvent mixtures. The effect of ethylene glycol on the binding of lactate dehydrogenase to an immobilised-AMP analogue.", "content": "The effect of the weak polarity-reducing agent, ethylene glycol, on the binding of pig heart lactate dehydrogenase to N6-(6-aminohexyl)-AMP-Sepharose has been investigated. In the absence of the reagent and under the conditions used, a non-specific interaction of the enzyme with the adsorbent led to recoveries of enzyme activity as low as 60% when the enzyme was eluted from the columns with a linear NADH gradient. The inclusion of low concentrations of ethylene glycol in column irrigants considerably improved the recovery of enzyme activity with quantitative recoveries being obtained in the presence of 20-30%. Concentrations of ethylene glycol about 35% altered the native conformation of lactate dehydrogenase and led to a decreased affinity for the immobilised ligand. Under these conditions, the altered protein fluorescence and decreased ability to bind NADH could be correlated with the chromatographic behaviour of the enzyme on columns of N6-(6-aminohexyl)-AMP-Sepharose. These effects were exploited to elute the enzyme from a column of immobilised-AMP with a linear gradient of ethylene glycol.", "contents": "Biospecific affinity chromatography in aqueous-organic cosolvent mixtures. The effect of ethylene glycol on the binding of lactate dehydrogenase to an immobilised-AMP analogue. The effect of the weak polarity-reducing agent, ethylene glycol, on the binding of pig heart lactate dehydrogenase to N6-(6-aminohexyl)-AMP-Sepharose has been investigated. In the absence of the reagent and under the conditions used, a non-specific interaction of the enzyme with the adsorbent led to recoveries of enzyme activity as low as 60% when the enzyme was eluted from the columns with a linear NADH gradient. The inclusion of low concentrations of ethylene glycol in column irrigants considerably improved the recovery of enzyme activity with quantitative recoveries being obtained in the presence of 20-30%. Concentrations of ethylene glycol about 35% altered the native conformation of lactate dehydrogenase and led to a decreased affinity for the immobilised ligand. Under these conditions, the altered protein fluorescence and decreased ability to bind NADH could be correlated with the chromatographic behaviour of the enzyme on columns of N6-(6-aminohexyl)-AMP-Sepharose. These effects were exploited to elute the enzyme from a column of immobilised-AMP with a linear gradient of ethylene glycol."} {"id": "PMID:170087", "title": "Metabolism of isolated kidney tubules. Independent actions of catecholamines on renal cyclic adenosine 3':5'-monophosphate levels and gluconeogenesis.", "content": "Isolated kidney cortex tubules from starved rats have been used to study the actions of catecholamines on renal adenosine 3':5' monophosphate (Ado-3':5'-P) levels and gluconeogenesis. In accordance with previous workers, norepinephrine was found to increase glucose formation from lactate and pyruvate and to a smaller degree from malate, succinate, fumarate and glutamine. The stimulatory effect of 0.5 muM norepinephrine was additive to that of 0.1 mM Ado-3':5-P, indicating an Ado-3':5'-P-independent mechanism of catecholamine action. The effects of parathyroid hormone and oleate on gluconeogenesis were also additive to that of norepinephrine. A comparative study of the actions of different catecholamine derivatives revealed that gluconeogenesis was stimulated in parallel to the alpha-adrenergic potency of the hormones, whereas Ado-3':5'-P levels were increased according to the known beta-stimulatory potency of the agents. Although isoproterenol was by far the most effective in raising Ado-3':5'-P levels, it was without effect on glucose formation from pyruvate, when added at 0.1 muM. At the same concentration, phenylephrine, which had no effect on Ado-3':5'-P levels, was the best stimulator of gluconeogenesis. The alpha-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a beta-blocking agent. The fact that the stimulatory effect of Ado-3':5'-P was also blocked by propranolol, indicated an unspecific mechanism of action of this substance. The results indicate that the stimulatory effect of catecholamines on renal gluconeogenesis are mediated by an alpha-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents.", "contents": "Metabolism of isolated kidney tubules. Independent actions of catecholamines on renal cyclic adenosine 3':5'-monophosphate levels and gluconeogenesis. Isolated kidney cortex tubules from starved rats have been used to study the actions of catecholamines on renal adenosine 3':5' monophosphate (Ado-3':5'-P) levels and gluconeogenesis. In accordance with previous workers, norepinephrine was found to increase glucose formation from lactate and pyruvate and to a smaller degree from malate, succinate, fumarate and glutamine. The stimulatory effect of 0.5 muM norepinephrine was additive to that of 0.1 mM Ado-3':5-P, indicating an Ado-3':5'-P-independent mechanism of catecholamine action. The effects of parathyroid hormone and oleate on gluconeogenesis were also additive to that of norepinephrine. A comparative study of the actions of different catecholamine derivatives revealed that gluconeogenesis was stimulated in parallel to the alpha-adrenergic potency of the hormones, whereas Ado-3':5'-P levels were increased according to the known beta-stimulatory potency of the agents. Although isoproterenol was by far the most effective in raising Ado-3':5'-P levels, it was without effect on glucose formation from pyruvate, when added at 0.1 muM. At the same concentration, phenylephrine, which had no effect on Ado-3':5'-P levels, was the best stimulator of gluconeogenesis. The alpha-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a beta-blocking agent. The fact that the stimulatory effect of Ado-3':5'-P was also blocked by propranolol, indicated an unspecific mechanism of action of this substance. The results indicate that the stimulatory effect of catecholamines on renal gluconeogenesis are mediated by an alpha-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents."} {"id": "PMID:170088", "title": "Muscle pyruvate kinase: interaction with substrates and analogues studied by difference spectroscopy. Comparative studies of the substrate-binding sites of various ATP phosphotransferases.", "content": "The substrate binding sites of pyruvate kinase have been studied by means of spectrophotometric investigations. Two binding sites, one for the nucleotide substrate and one for the acceptor, have been characterized. The interaction of nucleotide substrates with the enzyme, which is metal-dependent, results in a perturbation of the spectrum of the nucleotide chromophore characterized by hypochromic and red shift effects; the hydrophobicity of the nucleotide site was estimated by using a reporter group reagent, 2-(dansylamino)ethyl monophosphate. The comparison between the binding sites of several ATP phosphotransferases is discussed and some common features are reported.", "contents": "Muscle pyruvate kinase: interaction with substrates and analogues studied by difference spectroscopy. Comparative studies of the substrate-binding sites of various ATP phosphotransferases. The substrate binding sites of pyruvate kinase have been studied by means of spectrophotometric investigations. Two binding sites, one for the nucleotide substrate and one for the acceptor, have been characterized. The interaction of nucleotide substrates with the enzyme, which is metal-dependent, results in a perturbation of the spectrum of the nucleotide chromophore characterized by hypochromic and red shift effects; the hydrophobicity of the nucleotide site was estimated by using a reporter group reagent, 2-(dansylamino)ethyl monophosphate. The comparison between the binding sites of several ATP phosphotransferases is discussed and some common features are reported."} {"id": "PMID:170089", "title": "N-acetylglutamate 5-phosphotransferase of Pseudomonas aeruginosa. Purification and ligand-directed association-dissociation.", "content": "N-Acetylglutamate 5-phosphotransferase (ATP: N-acetyl-L-glutamate 5-phosphotransferase EC 2.7.2.8), the second enzyme of arginine biosynthesis, was purified over 2000-fold from Pseudomonas aeruginosa. The purification procedure involved a heat treatment, ammonium sulfate precipitation, and chromatography on DEAE-cellulose, Sephadex G-150, and hydroxyapatite. The purified enzyme was greater than 90% pure as judged by analytical polyacrylamide gel electrophoresis. A molecular weight of approximately 230000 was obtained by gel filtration. Electrophoresis in sodium dodecyl sulfate gels gave a single band corresponding to a molecular weight of 29000. Due to the capacity for self-association, the enzyme can exist in different states of aggregation depending on the nature of ligands and the concentrations of phosphate buffer. As estimated by gel filtration, the molecular weight was about 230000 in the presence of N-acetyl-L-glutamate. With L-arginine, the feedback inhibitor, and MgATP forms of smaller molecular weight (minimum of approximately 65000) were found. A concurrent change in the sedimentation coefficient as a function of ligands was demonstrated by sucrose gradient centrifugation. The synthesis of N-acetylglutamate 5-phosphotransferase was not repressed by exogenous L-arginine or its precursors.", "contents": "N-acetylglutamate 5-phosphotransferase of Pseudomonas aeruginosa. Purification and ligand-directed association-dissociation. N-Acetylglutamate 5-phosphotransferase (ATP: N-acetyl-L-glutamate 5-phosphotransferase EC 2.7.2.8), the second enzyme of arginine biosynthesis, was purified over 2000-fold from Pseudomonas aeruginosa. The purification procedure involved a heat treatment, ammonium sulfate precipitation, and chromatography on DEAE-cellulose, Sephadex G-150, and hydroxyapatite. The purified enzyme was greater than 90% pure as judged by analytical polyacrylamide gel electrophoresis. A molecular weight of approximately 230000 was obtained by gel filtration. Electrophoresis in sodium dodecyl sulfate gels gave a single band corresponding to a molecular weight of 29000. Due to the capacity for self-association, the enzyme can exist in different states of aggregation depending on the nature of ligands and the concentrations of phosphate buffer. As estimated by gel filtration, the molecular weight was about 230000 in the presence of N-acetyl-L-glutamate. With L-arginine, the feedback inhibitor, and MgATP forms of smaller molecular weight (minimum of approximately 65000) were found. A concurrent change in the sedimentation coefficient as a function of ligands was demonstrated by sucrose gradient centrifugation. The synthesis of N-acetylglutamate 5-phosphotransferase was not repressed by exogenous L-arginine or its precursors."} {"id": "PMID:170090", "title": "Spin-labeling studies of urea-treated leucine aminopeptidase.", "content": "1. Leucine aminopeptidase (EC 3-4-11-1) from bovine eye lens was spin-labeled at the most reactive thiol groups with 2,2,6,6-tetramethyl-4-[2-iodoacetamido]-piperidine-1-oxyl. 2. Electron spin resonance spectra show two spectral parts corresponding to two local conformational states in the environment of bound label. One state (A) exhibits a strong immobilizing effect on the mobility of the bound label whereas the other one (B) immobilizes weakly. Independently on the degree of labeling a ratio of A:B approximately 4:1 was estimated. In B a hydrophobic environment of label was observed. 3. Treatment of leucine aminopeptidase by 6.2 M urea leads to the following structural changes. a) An additional weakly immobilizing conformational state (B') with reduced hydrophobic interactions and increased mobility representing an unfolded conformational state appears. B' shows a time-dependent increase of its extent at the expense of B and A' (half conversion time about 0.5 h). The extent of this conformational change is larger, if the enzyme is additionally complexed with Mn2+. b) Mn2+ complexed with the protein is partly released producting hydrated Mn2+. c) After withdrawal of urea the observed conformational changes in leucine aminopeptidase are fully reversible, giving the initial ratio of A:B approximately 4:1 even after long incubation. 4. 6.2 M urea is not able to destroy the strongly immobilizing conformational state A completely.", "contents": "Spin-labeling studies of urea-treated leucine aminopeptidase. 1. Leucine aminopeptidase (EC 3-4-11-1) from bovine eye lens was spin-labeled at the most reactive thiol groups with 2,2,6,6-tetramethyl-4-[2-iodoacetamido]-piperidine-1-oxyl. 2. Electron spin resonance spectra show two spectral parts corresponding to two local conformational states in the environment of bound label. One state (A) exhibits a strong immobilizing effect on the mobility of the bound label whereas the other one (B) immobilizes weakly. Independently on the degree of labeling a ratio of A:B approximately 4:1 was estimated. In B a hydrophobic environment of label was observed. 3. Treatment of leucine aminopeptidase by 6.2 M urea leads to the following structural changes. a) An additional weakly immobilizing conformational state (B') with reduced hydrophobic interactions and increased mobility representing an unfolded conformational state appears. B' shows a time-dependent increase of its extent at the expense of B and A' (half conversion time about 0.5 h). The extent of this conformational change is larger, if the enzyme is additionally complexed with Mn2+. b) Mn2+ complexed with the protein is partly released producting hydrated Mn2+. c) After withdrawal of urea the observed conformational changes in leucine aminopeptidase are fully reversible, giving the initial ratio of A:B approximately 4:1 even after long incubation. 4. 6.2 M urea is not able to destroy the strongly immobilizing conformational state A completely."} {"id": "PMID:170091", "title": "Synthesis of coenzymically active soluble and insoluble macromolecularized NAD+ derivatives.", "content": "Alkylation at N-1 of the NAD+ adenine ring with 3,4-epoxybutanoic acid, followed by chemical reduction to the alkali-stable NADH form and alkaline Dimroth rearrangement, gave the NADH derivative alkylated at the exocyclic adenine amino group. Enzymic reoxidation of the latter derivative gave nicotinamide-6-(2-hydroxy-3-carboxypropylamino)purine dinucleotide, a functionalized NAD+ analogue carrying an omega-carboxyalkyl side-chain at the exocyclic adenine amino group. Carbodiimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexyl-Sepharose) polymers gave the corresponding macromolecularized NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine and polylysine analogues showed a substantial degree of efficiency relative to free NAD+ with rabbit muscle lactate dehydrogenase (60 and 25% respectively) but a lower one with yeast alcohol dehydrogenase and Bacillus subtilis alanine dehydrogenase (2-7%). The polyethyleneimine derivative entrapped in cellulose triacetate fibres together with the lactate dehydrogenase was operationally stable during repetitive use.", "contents": "Synthesis of coenzymically active soluble and insoluble macromolecularized NAD+ derivatives. Alkylation at N-1 of the NAD+ adenine ring with 3,4-epoxybutanoic acid, followed by chemical reduction to the alkali-stable NADH form and alkaline Dimroth rearrangement, gave the NADH derivative alkylated at the exocyclic adenine amino group. Enzymic reoxidation of the latter derivative gave nicotinamide-6-(2-hydroxy-3-carboxypropylamino)purine dinucleotide, a functionalized NAD+ analogue carrying an omega-carboxyalkyl side-chain at the exocyclic adenine amino group. Carbodiimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexyl-Sepharose) polymers gave the corresponding macromolecularized NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine and polylysine analogues showed a substantial degree of efficiency relative to free NAD+ with rabbit muscle lactate dehydrogenase (60 and 25% respectively) but a lower one with yeast alcohol dehydrogenase and Bacillus subtilis alanine dehydrogenase (2-7%). The polyethyleneimine derivative entrapped in cellulose triacetate fibres together with the lactate dehydrogenase was operationally stable during repetitive use."} {"id": "PMID:170092", "title": "12-(9-Anthroyl)stearic acid, a fluorescent probe for the ubiquinone region of the mitochondrial membrane.", "content": "1. 12-(9-Anthroyl)stearic acid can be incorporated into mitochondrial membranes. 2. The fluorescence properties of the membrane-bound probe are different from those of the free molecule. 3. The intensity of emission and fluorescence life-time of the probe is enhanced when, in the presence of substrate, the electron-transport chain is reduced. 4. This change in intensity has been demonstrated to be a result of collisional quenching by oxidised ubiquinone in the oxidised membrane but not when the respiratory chain is in the reduced state. 5. In pulsing anaerobic mitochondria with oxygen the rate of the fluorescence change is found to be slower than the rate of ubiquinone oxidation, suggesting that the probe detects a structural transition in the mitochondrial inner membrane. 6. This transition results in a constraint on ubiquinone motion in the reduced system. Model experiments, using lipid dispersions, have been carried out to test some of the interpretations.", "contents": "12-(9-Anthroyl)stearic acid, a fluorescent probe for the ubiquinone region of the mitochondrial membrane. 1. 12-(9-Anthroyl)stearic acid can be incorporated into mitochondrial membranes. 2. The fluorescence properties of the membrane-bound probe are different from those of the free molecule. 3. The intensity of emission and fluorescence life-time of the probe is enhanced when, in the presence of substrate, the electron-transport chain is reduced. 4. This change in intensity has been demonstrated to be a result of collisional quenching by oxidised ubiquinone in the oxidised membrane but not when the respiratory chain is in the reduced state. 5. In pulsing anaerobic mitochondria with oxygen the rate of the fluorescence change is found to be slower than the rate of ubiquinone oxidation, suggesting that the probe detects a structural transition in the mitochondrial inner membrane. 6. This transition results in a constraint on ubiquinone motion in the reduced system. Model experiments, using lipid dispersions, have been carried out to test some of the interpretations."} {"id": "PMID:170093", "title": "Flavocytochrome b2: kinetic studies by absorbance and electron-paramagnetic-resonance spectroscopy of electron distribution among prosthetic groups.", "content": "The reduction by L-lactate of the prosthetic groups of flavocytochrome b2 (L-lactate cytochrome c oxidoreductase from aerobic yeast, a tetrameric molecule containing one haem and one flavin mononucleotide per protomer) was reinvestigated. It was confirmed that the enzyme ultimately takes up 3 electrons per protomer from this 2-electron donor. Stopped-flow absorbance data at an haem isosbestic point to follow the oxidized flavin and in a haem band indicate that, under the conditions used, haem and flavin reduction time courses are indistinguishable, both being biphasic (phases I and II). Comparison with electron paramagnetic resonance data (Fe3+ haem and flavosemiquinone signals) led to a complete description at 24 degrees C of the time courses of the various reduction states of the prosthetic groups. It has been previously demonstrated (Morton and Sturtevant, 1964) that, after the formation of the enzyme-substrate complex, the electron transfer to the enzyme takes place as the first and rate-limiting step of the turnover. In the present study, an initial burst of fully reduced flavin, of small amplitude, is detected at the very beginning of phase I (before 6 ms). The redox forms which accumulate thereafter till the end of phase I (30-35 ms) are the reduced haem (up to 80%), the flavin semiquinone (up to 50%) and the fully reduced flavin (from 25% up to 35%); the total of electrons distributed at the end of phase I is about 2 per protomer meaning that, in this phase, each enzyme site acts as a 2-electron and not a 3-electron acceptor. A 2-electron flow as the limiting step during phase I with the rate constant kI accounts for the steady-state electron flow during catalysis. Phase I is followed by the much slower phase II which corresponds to the entry of the third electron and cannot be involved in the turnover. The interpretation of the results are given as a scheme, with the proper rate constants, allowing a satisfactory fitting of experimental data by simulation. Among the elementary steps required are a rapid distribution of one electron from reduced flavin to the haem, a rapid interprotomers dismutation between couples of flavin semiquinone regenerating two oxidized flavin per tetramer. The very low reactivity of the latter for the entry of the third electron per protomer is tentatively explained by the occurrence of a slow additional step limiting the final reduction reaction. It was observed that, over phase I and the beginning of phase II, from 15 to 200 ms, all the redox species remain apparently under equilibrium conditions. Parallel studies (titrations of flavocytochrome b2 by L-lactate) showed that the set of equilibrium parameters relative to haem and flavin species is significantly different in the \"final\" equilibrium (after 30 s) from that in the time interval 15-200 ms. Such an anomaly suggests a conformation change takes place very slowly in the molecule after the acceptance of the first two electrons per protomer.", "contents": "Flavocytochrome b2: kinetic studies by absorbance and electron-paramagnetic-resonance spectroscopy of electron distribution among prosthetic groups. The reduction by L-lactate of the prosthetic groups of flavocytochrome b2 (L-lactate cytochrome c oxidoreductase from aerobic yeast, a tetrameric molecule containing one haem and one flavin mononucleotide per protomer) was reinvestigated. It was confirmed that the enzyme ultimately takes up 3 electrons per protomer from this 2-electron donor. Stopped-flow absorbance data at an haem isosbestic point to follow the oxidized flavin and in a haem band indicate that, under the conditions used, haem and flavin reduction time courses are indistinguishable, both being biphasic (phases I and II). Comparison with electron paramagnetic resonance data (Fe3+ haem and flavosemiquinone signals) led to a complete description at 24 degrees C of the time courses of the various reduction states of the prosthetic groups. It has been previously demonstrated (Morton and Sturtevant, 1964) that, after the formation of the enzyme-substrate complex, the electron transfer to the enzyme takes place as the first and rate-limiting step of the turnover. In the present study, an initial burst of fully reduced flavin, of small amplitude, is detected at the very beginning of phase I (before 6 ms). The redox forms which accumulate thereafter till the end of phase I (30-35 ms) are the reduced haem (up to 80%), the flavin semiquinone (up to 50%) and the fully reduced flavin (from 25% up to 35%); the total of electrons distributed at the end of phase I is about 2 per protomer meaning that, in this phase, each enzyme site acts as a 2-electron and not a 3-electron acceptor. A 2-electron flow as the limiting step during phase I with the rate constant kI accounts for the steady-state electron flow during catalysis. Phase I is followed by the much slower phase II which corresponds to the entry of the third electron and cannot be involved in the turnover. The interpretation of the results are given as a scheme, with the proper rate constants, allowing a satisfactory fitting of experimental data by simulation. Among the elementary steps required are a rapid distribution of one electron from reduced flavin to the haem, a rapid interprotomers dismutation between couples of flavin semiquinone regenerating two oxidized flavin per tetramer. The very low reactivity of the latter for the entry of the third electron per protomer is tentatively explained by the occurrence of a slow additional step limiting the final reduction reaction. It was observed that, over phase I and the beginning of phase II, from 15 to 200 ms, all the redox species remain apparently under equilibrium conditions. Parallel studies (titrations of flavocytochrome b2 by L-lactate) showed that the set of equilibrium parameters relative to haem and flavin species is significantly different in the \"final\" equilibrium (after 30 s) from that in the time interval 15-200 ms. Such an anomaly suggests a conformation change takes place very slowly in the molecule after the acceptance of the first two electrons per protomer."} {"id": "PMID:170094", "title": "Purification of rheumatoid synovial collagenase and its action on soluble and insoluble collagen.", "content": "1. The neutral collagenase released into the culture medium by explants of ehrumatoid synovial tissue has been purified by ultrafiltration and column chromatography, utilising Sephadex G-200, Sephadex QAE A-50 and Sephadex G-100 superfine. 2. The final collagenase preparation had a specific activity against thermally reconstituted collagen fibrils of 312 mug collagen degraded min-1 mg enzyme protein-1, representing more than a 1000-fold increase over that of the active culture medium. 3. Electrophoresis in polyacrylamide disc-gels with and without sodium dodecyl sulphate showed the enzyme to migrate as a single protein band. Elution experiments from polyacrylamide gels and chromatography columns have provided no evidence for the existence of more than one collagenase. 4. The molecular weight of the enzyme, as determined by dodecylsulphate-polyacrylamide gel electrophoresis, was 33000. 5. Data obtained from sutdies with the ion-exchange resin and from gel electrophoresis in acid and alkaline buffer systems suggested a basically charged enzyme. 6. It did not hydrolyse the synthetic collagen peptide Pz-Pro-Leu-Gly-Pro-D-Arg and non-specific protease activity was absent. 7. The collagenase attacked undenatured collagen in solution at 25 degrees C resulting in a 58% loss of viscosity and producing the two characteristic products TCA(3/4) and TCB(1/4). 8. At 37 degrees C and pH 8.0 both reconstituted collagen fibrils and gelatin were degraded to peptides of less than 10000 molecular weight. 9. As judged by the release of soluble hydroxyproline peptides and electron microscopic appearances the enzyme degraded human insoluble collagens derived from tendon and soft juxta-articular tissues although rates of attack were less than with reconstituted fibrils. 10. The data suggests that pure rheumatoid synovial collagenase at 37 degrees C and neutral pH can degrade gelatin, reconstituted fibrils and insoluble collagens without the intervention of non-specific proteases. 11. The different susceptibilities of various collagenous substrates to collagenase attack are discussed.", "contents": "Purification of rheumatoid synovial collagenase and its action on soluble and insoluble collagen. 1. The neutral collagenase released into the culture medium by explants of ehrumatoid synovial tissue has been purified by ultrafiltration and column chromatography, utilising Sephadex G-200, Sephadex QAE A-50 and Sephadex G-100 superfine. 2. The final collagenase preparation had a specific activity against thermally reconstituted collagen fibrils of 312 mug collagen degraded min-1 mg enzyme protein-1, representing more than a 1000-fold increase over that of the active culture medium. 3. Electrophoresis in polyacrylamide disc-gels with and without sodium dodecyl sulphate showed the enzyme to migrate as a single protein band. Elution experiments from polyacrylamide gels and chromatography columns have provided no evidence for the existence of more than one collagenase. 4. The molecular weight of the enzyme, as determined by dodecylsulphate-polyacrylamide gel electrophoresis, was 33000. 5. Data obtained from sutdies with the ion-exchange resin and from gel electrophoresis in acid and alkaline buffer systems suggested a basically charged enzyme. 6. It did not hydrolyse the synthetic collagen peptide Pz-Pro-Leu-Gly-Pro-D-Arg and non-specific protease activity was absent. 7. The collagenase attacked undenatured collagen in solution at 25 degrees C resulting in a 58% loss of viscosity and producing the two characteristic products TCA(3/4) and TCB(1/4). 8. At 37 degrees C and pH 8.0 both reconstituted collagen fibrils and gelatin were degraded to peptides of less than 10000 molecular weight. 9. As judged by the release of soluble hydroxyproline peptides and electron microscopic appearances the enzyme degraded human insoluble collagens derived from tendon and soft juxta-articular tissues although rates of attack were less than with reconstituted fibrils. 10. The data suggests that pure rheumatoid synovial collagenase at 37 degrees C and neutral pH can degrade gelatin, reconstituted fibrils and insoluble collagens without the intervention of non-specific proteases. 11. The different susceptibilities of various collagenous substrates to collagenase attack are discussed."} {"id": "PMID:170095", "title": "Early nucleolar preribosomal RNA - protein in mammalian cells.", "content": "Early steps of ribosomal maturation have been studied by analysis of nucleolar extracts using different extraction procedures. Early 45-S nucleolar RNA is found to be associated with slowly sedimenting elements, distinct from previously described 80-S and 55-S nucleolar preribosomes. This early 45-S RNA has been shown to be of preribosomal type according to the following criteria. (a) When hybridized with nucleolar DNA, competition with rRNA can be observed; (b) its biosynthesis is sensitive to low doses of actinomycin D; (c) it is methylated at an early stage; (d) it contains no linked poly(A) segments. This early 45-S RNA seems to be specifically linked with proteins. The protein content of these early RNA-protein complexes is significantly lower than that for 80-S preribosomes. 45-S RNA sensitivity to nucleolytic activities that can take place in the course of preribosome extraction has been found to be higher in these RNA-protein complexes than in 80-S preribosomes. Identical results were obtained when different mammalian cell species were studied (rat, hamster, or HeLa cells).", "contents": "Early nucleolar preribosomal RNA - protein in mammalian cells. Early steps of ribosomal maturation have been studied by analysis of nucleolar extracts using different extraction procedures. Early 45-S nucleolar RNA is found to be associated with slowly sedimenting elements, distinct from previously described 80-S and 55-S nucleolar preribosomes. This early 45-S RNA has been shown to be of preribosomal type according to the following criteria. (a) When hybridized with nucleolar DNA, competition with rRNA can be observed; (b) its biosynthesis is sensitive to low doses of actinomycin D; (c) it is methylated at an early stage; (d) it contains no linked poly(A) segments. This early 45-S RNA seems to be specifically linked with proteins. The protein content of these early RNA-protein complexes is significantly lower than that for 80-S preribosomes. 45-S RNA sensitivity to nucleolytic activities that can take place in the course of preribosome extraction has been found to be higher in these RNA-protein complexes than in 80-S preribosomes. Identical results were obtained when different mammalian cell species were studied (rat, hamster, or HeLa cells)."} {"id": "PMID:170096", "title": "Nuclear protein-kinase activity in perfused rat liver stimulated with dibutyryl-adenosine cyclic 3':5'-monophosphate.", "content": "Cytoplasmic and nuclear protein kinase activities from perfused rat liver have been studied in response to dibutyryl-adenosine cyclic 3':5'-monophosphate added at a concentration that stimulates hepatic gluconeogenesis (100 muM). Total nuclear protein kinase, as assayed using a mixed histone fraction as phosphate acceptor, is increased by 5-fold within 8 min of the addition of cyclic nucleotide to the perfusate. In contrast the total cytoplasmic protein kinase activity is decreased to 50% of the control value. The protein substrate specificity of the protein kinase that is present in the nucleus in response to dibutyryl-adenosine cyclic 3':5'-monophosphate stimulation is similar to that of cytoplasmic, adenosine cyclic 3':5'-monophosphate-dependent, protein kinase but is distinct from that of the enzyme(s) present in control nuclei. The predominant species to protein kinase from stimulated nuclei has a sedimentation constant of 3.9 S. This value is identical to that of the catalytic subunit of cytoplasmic adenosine 3':5'-monophosphate-dependent protein kinase. These data suggest that some of the effects of adenosine 3':5'-monophosphate on nuclear events may be mediated through its interaction with the inactive protein kinase holoenzyme in the cytoplasm and the subsequent redistribution of the active catalytic subunits generated by this interaction.", "contents": "Nuclear protein-kinase activity in perfused rat liver stimulated with dibutyryl-adenosine cyclic 3':5'-monophosphate. Cytoplasmic and nuclear protein kinase activities from perfused rat liver have been studied in response to dibutyryl-adenosine cyclic 3':5'-monophosphate added at a concentration that stimulates hepatic gluconeogenesis (100 muM). Total nuclear protein kinase, as assayed using a mixed histone fraction as phosphate acceptor, is increased by 5-fold within 8 min of the addition of cyclic nucleotide to the perfusate. In contrast the total cytoplasmic protein kinase activity is decreased to 50% of the control value. The protein substrate specificity of the protein kinase that is present in the nucleus in response to dibutyryl-adenosine cyclic 3':5'-monophosphate stimulation is similar to that of cytoplasmic, adenosine cyclic 3':5'-monophosphate-dependent, protein kinase but is distinct from that of the enzyme(s) present in control nuclei. The predominant species to protein kinase from stimulated nuclei has a sedimentation constant of 3.9 S. This value is identical to that of the catalytic subunit of cytoplasmic adenosine 3':5'-monophosphate-dependent protein kinase. These data suggest that some of the effects of adenosine 3':5'-monophosphate on nuclear events may be mediated through its interaction with the inactive protein kinase holoenzyme in the cytoplasm and the subsequent redistribution of the active catalytic subunits generated by this interaction."} {"id": "PMID:170097", "title": "Sequence determination of 5'-terminal and 3'-terminal T1 oligonucleotides of 18-S ribosomal RNA of a mouse cell line (L 5178 Y).", "content": "The 5' and 3'-terminal oligonucleotides of 18-S ribosomal RNA of L 5178 Y (a mouse cell line) obtained after total T1 ribonuclease hydrolysis were isolated by a diagonal procedure. They were localized on the fingerprint of T1-ribonuclease-hydrolysed 18-S RNA. These two oligonucleotides were partially hydrolysed by snake venom and spleen phsophodiesterases and resulting products were fractionated bidimensionally. Their base compositions were determined by total hydrolysis with piperidine or snake venom phosphodiesterase. From these results the following sequences were deduced: pU-A-C-C-U-G for the 5'-terminal oligonucleotide and G-A-U-C-A-U-U-Aoh for the 3'-terminal oligonucleotide. Quantitative studies indicated that these sequences represent at least 70% for the 5' oligonucleotide and 85% for the 3' oligonucleotide of the terminal sequences of the 18-S RNA.", "contents": "Sequence determination of 5'-terminal and 3'-terminal T1 oligonucleotides of 18-S ribosomal RNA of a mouse cell line (L 5178 Y). The 5' and 3'-terminal oligonucleotides of 18-S ribosomal RNA of L 5178 Y (a mouse cell line) obtained after total T1 ribonuclease hydrolysis were isolated by a diagonal procedure. They were localized on the fingerprint of T1-ribonuclease-hydrolysed 18-S RNA. These two oligonucleotides were partially hydrolysed by snake venom and spleen phsophodiesterases and resulting products were fractionated bidimensionally. Their base compositions were determined by total hydrolysis with piperidine or snake venom phosphodiesterase. From these results the following sequences were deduced: pU-A-C-C-U-G for the 5'-terminal oligonucleotide and G-A-U-C-A-U-U-Aoh for the 3'-terminal oligonucleotide. Quantitative studies indicated that these sequences represent at least 70% for the 5' oligonucleotide and 85% for the 3' oligonucleotide of the terminal sequences of the 18-S RNA."} {"id": "PMID:170098", "title": "Protein kinase of bacteriophage T7. 1. Purification.", "content": "A protein kinase, ATP:protein phosphotransferase (EC 2.7.1.37) was detected in Escherichia coli after infection with bacteriophage T7. The enzyme was purified from the ribosomal wash fraction by conventional methods, affinity chromatography on Cibacron blue and on lysozyme coupled to Sepharose, and by cellogel electrophoresis. An approximately 5000-fold purification was achieved.", "contents": "Protein kinase of bacteriophage T7. 1. Purification. A protein kinase, ATP:protein phosphotransferase (EC 2.7.1.37) was detected in Escherichia coli after infection with bacteriophage T7. The enzyme was purified from the ribosomal wash fraction by conventional methods, affinity chromatography on Cibacron blue and on lysozyme coupled to Sepharose, and by cellogel electrophoresis. An approximately 5000-fold purification was achieved."} {"id": "PMID:170099", "title": "Induction of polyadenylate polymerase and differentiation in neuroblastoma cells.", "content": "Treatment of neuroblastoma cells with dibutyryl-adenosine 3':5'-monophosphate or adenine induced axon formation and a three-fold increase in the polyadenylate, poly(A), content of the polysomal mRNA. The extracted poly(A) contained 90% adenylic acid and showed a mobility of 6--7 S in dodecylsulfate-polyacrylamide gel electrophoresis. Treatment with dibutyryl-adenosine 3':5'-monophosphate or adenine, also induced a 4--6 fold increase in a nuclear enzymic activity that incorporated [3H]ATP to an acid-insoluble polymer in a cell-free system. This polymer, like poly(A) extracted from the polysomal mRNA, was bound at high salt concentration to nitrocellulose filters. [3H]ATP incorporation was Mg2+-dependent, sensitive to ribonuclease and EDTA and resistant to deoxyribonuclease and actinomycin D. There was no incorporation of [3H]UTP or [3H]dTTP and addition of TUP, CTP and GTP did not increase the incorporation of [3H]ATP. 5-Bromodeoxyuridine induced axon formation of neuroblastoma cells and poly(A) polymerase activity, without increasing the poly(A) content in the polysomal mRNA. The results indicate that induction of axon formation of neuroblastoma cells is associated with an increase in the activity of poly(A) polymerase. It is suggested that the induction of this enzyme may be generally involved in cell differentiation.", "contents": "Induction of polyadenylate polymerase and differentiation in neuroblastoma cells. Treatment of neuroblastoma cells with dibutyryl-adenosine 3':5'-monophosphate or adenine induced axon formation and a three-fold increase in the polyadenylate, poly(A), content of the polysomal mRNA. The extracted poly(A) contained 90% adenylic acid and showed a mobility of 6--7 S in dodecylsulfate-polyacrylamide gel electrophoresis. Treatment with dibutyryl-adenosine 3':5'-monophosphate or adenine, also induced a 4--6 fold increase in a nuclear enzymic activity that incorporated [3H]ATP to an acid-insoluble polymer in a cell-free system. This polymer, like poly(A) extracted from the polysomal mRNA, was bound at high salt concentration to nitrocellulose filters. [3H]ATP incorporation was Mg2+-dependent, sensitive to ribonuclease and EDTA and resistant to deoxyribonuclease and actinomycin D. There was no incorporation of [3H]UTP or [3H]dTTP and addition of TUP, CTP and GTP did not increase the incorporation of [3H]ATP. 5-Bromodeoxyuridine induced axon formation of neuroblastoma cells and poly(A) polymerase activity, without increasing the poly(A) content in the polysomal mRNA. The results indicate that induction of axon formation of neuroblastoma cells is associated with an increase in the activity of poly(A) polymerase. It is suggested that the induction of this enzyme may be generally involved in cell differentiation."} {"id": "PMID:170100", "title": "Study of coenzyme binding site of octopine dehydrogenase using analogues of NAD+.", "content": "The binding of the coenzyme to octopine dehydrogenase was investigated by kinetic and spectroscopic studies using different analogues of NAD+. The analogues employed were fragments of the coenzyme molecule and dinucleotides modified on the purine or the pyridine ring. The binding of ADPribose is sufficient to induce local conformational changes necessary for the good positioning of substrates. AMP, ADP, NMN+ and NMNH do not show this effect. Analogues modified on the purine ring such as nicotinamide deaminoadenine dinucleotide, nicotinamide--8-bromoadenine dinucleotide, nicotinamide--8-thioadenine dinucleotide and nicotinamide 1: N6-ethenoadenine dinucleotide bind to the enzyme and give catalytically active ternary complexes. Modifications of the pyridine ring show an important effect on the binding of the coenzyme as well as on the formation of ternary complexes. Thus, the carboxamide group can well be replaced by an acetyl group and also, though less efficiently, by a formyl or cyano group. However more bulky substituents such as thio, chloroacetyl or propionyl groups prevent the binding. The analogues bearing a methyl group in the 4 or 5 position, which are competitive inhibitors, are able to give binary by not ternary complexes. The case of 1,4,5,6-tetrahydronicotinamide--adenine dinucleotide which does not give ternary complexes like NADH is discussed. The above findings show that the pyridine and adenine parts are both involved in the binding of the coenzyme and of the substrate to octopine dehydrogenase. The nicotinamide binding site of this enzyme seems to be the most specific and restricted one among the dehydrogenases so far described. The protective effects of coenzyme analogues towards essential -SH group were also studied.", "contents": "Study of coenzyme binding site of octopine dehydrogenase using analogues of NAD+. The binding of the coenzyme to octopine dehydrogenase was investigated by kinetic and spectroscopic studies using different analogues of NAD+. The analogues employed were fragments of the coenzyme molecule and dinucleotides modified on the purine or the pyridine ring. The binding of ADPribose is sufficient to induce local conformational changes necessary for the good positioning of substrates. AMP, ADP, NMN+ and NMNH do not show this effect. Analogues modified on the purine ring such as nicotinamide deaminoadenine dinucleotide, nicotinamide--8-bromoadenine dinucleotide, nicotinamide--8-thioadenine dinucleotide and nicotinamide 1: N6-ethenoadenine dinucleotide bind to the enzyme and give catalytically active ternary complexes. Modifications of the pyridine ring show an important effect on the binding of the coenzyme as well as on the formation of ternary complexes. Thus, the carboxamide group can well be replaced by an acetyl group and also, though less efficiently, by a formyl or cyano group. However more bulky substituents such as thio, chloroacetyl or propionyl groups prevent the binding. The analogues bearing a methyl group in the 4 or 5 position, which are competitive inhibitors, are able to give binary by not ternary complexes. The case of 1,4,5,6-tetrahydronicotinamide--adenine dinucleotide which does not give ternary complexes like NADH is discussed. The above findings show that the pyridine and adenine parts are both involved in the binding of the coenzyme and of the substrate to octopine dehydrogenase. The nicotinamide binding site of this enzyme seems to be the most specific and restricted one among the dehydrogenases so far described. The protective effects of coenzyme analogues towards essential -SH group were also studied."} {"id": "PMID:170101", "title": "Chlorinating ability of human phagocytosing leucocytes.", "content": "The course of chlorination in neutrophilic granulocytes has been shown. The process of 36Cl incorporation occurs during and after the engulfment of bacteria by granulocytes. Incorported radioactivity was found in insoluble fractions. The myeloperoxidase obtained from neutrophils catalyzes chlorination of protein (bovine serum albumin) and bacteria (Staphylococcus epidermidis) in the presence of hydrogen peroxide and chloride. The products of chlorination are insoluble. Chlorination in neutrophils is inhibited by the iodide and myeloperoxidase inhibitors azide and cyanide. A quantitative method of determination of biological chlorination in cells has been devised.", "contents": "Chlorinating ability of human phagocytosing leucocytes. The course of chlorination in neutrophilic granulocytes has been shown. The process of 36Cl incorporation occurs during and after the engulfment of bacteria by granulocytes. Incorported radioactivity was found in insoluble fractions. The myeloperoxidase obtained from neutrophils catalyzes chlorination of protein (bovine serum albumin) and bacteria (Staphylococcus epidermidis) in the presence of hydrogen peroxide and chloride. The products of chlorination are insoluble. Chlorination in neutrophils is inhibited by the iodide and myeloperoxidase inhibitors azide and cyanide. A quantitative method of determination of biological chlorination in cells has been devised."} {"id": "PMID:170102", "title": "Prostaglandin 15-hydroxy dehydrogenase from human placenta.", "content": "The enzyme system prostaglandin 15-hydroxy dehydrogenase, which catalyzes the inactivation of all biologically active prostaglandins, has been purified 1270-fold from human placenta. Kinetic studies on the enzyme have provided information on a well-organized control mechanism to avoid prostaglandin accumulation and for a fast prostaglandin degradation. 15-Ketoprostaglandin E2 and 13,14-dihydro-15-ketoprostaglandin E2 inhibit prostaglandin 15-hydroxy dehydrogenase non-competitively with respect to prostaglandin E2. The rate equation of enzyme reaction for two substrates was used for determination of the equilibrium constant and Michaelis constants of the enzyme. The following kinetic constants for prostaglandin 15-hydroxy dehydrogenase have been found. The equilibrium constant with repect to prostaglandin E2 is 18 muM, the Michaelis constant Km for prostaglandin E2 is 1 muM for NAD+ 44muM. The inhibition constants for 15-ketoprostaglandin E2 ar Ki(slope) = 70 muM, Ki(intercept) = 150 muM, and for 13,14-dihydro-15-ketoprostaglandin E2 Ki(slope) = 80 muM, and Ki(intercept) = 150 muM. The maximal velocity for the forward reaction is V1 = 0.45 mumol/min. These kinetic data exclude a random or ping-pong mechanism, and also a Theorell-Chance type as suggested by Braithwaite and Jarabak. We propose, therefore, a sequential ordered mechanism. The isoelectric point for prostaglandin 15-hydroxy dehydrogenase is at pH 5.35, judged by isoelectric focusing.", "contents": "Prostaglandin 15-hydroxy dehydrogenase from human placenta. The enzyme system prostaglandin 15-hydroxy dehydrogenase, which catalyzes the inactivation of all biologically active prostaglandins, has been purified 1270-fold from human placenta. Kinetic studies on the enzyme have provided information on a well-organized control mechanism to avoid prostaglandin accumulation and for a fast prostaglandin degradation. 15-Ketoprostaglandin E2 and 13,14-dihydro-15-ketoprostaglandin E2 inhibit prostaglandin 15-hydroxy dehydrogenase non-competitively with respect to prostaglandin E2. The rate equation of enzyme reaction for two substrates was used for determination of the equilibrium constant and Michaelis constants of the enzyme. The following kinetic constants for prostaglandin 15-hydroxy dehydrogenase have been found. The equilibrium constant with repect to prostaglandin E2 is 18 muM, the Michaelis constant Km for prostaglandin E2 is 1 muM for NAD+ 44muM. The inhibition constants for 15-ketoprostaglandin E2 ar Ki(slope) = 70 muM, Ki(intercept) = 150 muM, and for 13,14-dihydro-15-ketoprostaglandin E2 Ki(slope) = 80 muM, and Ki(intercept) = 150 muM. The maximal velocity for the forward reaction is V1 = 0.45 mumol/min. These kinetic data exclude a random or ping-pong mechanism, and also a Theorell-Chance type as suggested by Braithwaite and Jarabak. We propose, therefore, a sequential ordered mechanism. The isoelectric point for prostaglandin 15-hydroxy dehydrogenase is at pH 5.35, judged by isoelectric focusing."} {"id": "PMID:170103", "title": "Characterization of oxytocin receptors on isolated rat fat cells.", "content": "The binding of 3H-labelled neurohypophyseal nonapeptide hormone, oxytocin, to isolated rat fat cells has been measured under conditions where this compound elicits the known activation of glucose oxidation by these cells, called \"insulin-like\" action. Uptake by the cells of the [3H]peptide as a function of various concentrations of the hormone in the medium indicated the presence of two classes of binding sites with different apparent affinities and capacities. The sites of the first type exhibit a rather high affinity, but low capacity, for oxytocin (5 nM; 3 X 10(4) sited per cell) and appear to be saturable under a reversible process. Evaluation of dose-response relationships suggest that they may be directly related to the measured biological response (i.e. activation of the glucose to 14CO2 conversion). Competition experiments show that [3H]oxytocin binding to the cells remains constant within a large range of insulin concentrations. The apparent capacity of different hormone analogs to compete with oxytocin for binding to this class of receptors has been evaluated and compared with the measured insulin-like activity of these different compounds. The sites of the second category have significantly lower affinity, but higher capacity for oxytocin, and were found to be not saturable under the experimental conditions. [3H]Oxytocin uptake by ghosts prepared from the isolated fat cells showed striking similarities to the binding process described for whole cells, although the affinity and total capacity of the former were found to be slightly lower. The basal and adrenalin-stimulated adenylate cyclase of these fractions appeared to be unaffected by various concentrations of oxytocin. It is concluded that there may exist on the rat fat cell membranes a discrete number of oxytocin receptors possessing high specificity for oxytocin and exhibiting affinities and kinetic behaviour similar to those of other characterized oxytocin receptors. They are believed to be independent of the other hormonal receptors of the rat fact cells.", "contents": "Characterization of oxytocin receptors on isolated rat fat cells. The binding of 3H-labelled neurohypophyseal nonapeptide hormone, oxytocin, to isolated rat fat cells has been measured under conditions where this compound elicits the known activation of glucose oxidation by these cells, called \"insulin-like\" action. Uptake by the cells of the [3H]peptide as a function of various concentrations of the hormone in the medium indicated the presence of two classes of binding sites with different apparent affinities and capacities. The sites of the first type exhibit a rather high affinity, but low capacity, for oxytocin (5 nM; 3 X 10(4) sited per cell) and appear to be saturable under a reversible process. Evaluation of dose-response relationships suggest that they may be directly related to the measured biological response (i.e. activation of the glucose to 14CO2 conversion). Competition experiments show that [3H]oxytocin binding to the cells remains constant within a large range of insulin concentrations. The apparent capacity of different hormone analogs to compete with oxytocin for binding to this class of receptors has been evaluated and compared with the measured insulin-like activity of these different compounds. The sites of the second category have significantly lower affinity, but higher capacity for oxytocin, and were found to be not saturable under the experimental conditions. [3H]Oxytocin uptake by ghosts prepared from the isolated fat cells showed striking similarities to the binding process described for whole cells, although the affinity and total capacity of the former were found to be slightly lower. The basal and adrenalin-stimulated adenylate cyclase of these fractions appeared to be unaffected by various concentrations of oxytocin. It is concluded that there may exist on the rat fat cell membranes a discrete number of oxytocin receptors possessing high specificity for oxytocin and exhibiting affinities and kinetic behaviour similar to those of other characterized oxytocin receptors. They are believed to be independent of the other hormonal receptors of the rat fact cells."} {"id": "PMID:170104", "title": "Epinephrine-binding plasma-membrane antigens in rat liver.", "content": "Detergent extracts of isolated rat liver plasma membranes were analysed in two-dimensional immunoelectrophoresis against antiserum to plasma membranes. Enzyme staining of the immunoprecipitates revealed the presence of about ten antigens with nucleoside di- and triphosphatase activity. Most of these were earlier shown also to be NADH-neotetrazolium reductase active. In addition, two of these antigens exhibited L-leucyl-beta-naphthylamidase activity. As judged from autoradiography these plasma membrane antigens earlier characterized as multienzyme complexes bound [14C]epinephrine, and the same antigens were labelled regardless of whether membranes or membrane extracts were incubated with the radioactive hormone. The specificity of this binding was established in displacement experiments with unlabelled hormones or their analogues. Another hormone-binding antigen, also identified in the plasma membrane extract did not exhibit any known enzyme activity while three antigens with different enzyme activities had no epinephrine-binding capacity. [14C]Epinephrine-labelled plasma membrane extracts were chromatographed on Sepharose 4B and the fractions obtained were analysed in two-dimensional immunoelectrophoresis combined with autoradiography. Nucleoside di- and triphosphatases of high molecular weights (5000000) were associated with L-leucyl-beta-naphthylamidase activity, while no such associations were detected in a lower molecular weight region (70000). Further immunological studies on the various fractionated antigens provided evidence that at least two of them occurred in both low and high molecular weight fractions. Hormone-binding membrane components in varying concentrations were found throughout the eluted extract.", "contents": "Epinephrine-binding plasma-membrane antigens in rat liver. Detergent extracts of isolated rat liver plasma membranes were analysed in two-dimensional immunoelectrophoresis against antiserum to plasma membranes. Enzyme staining of the immunoprecipitates revealed the presence of about ten antigens with nucleoside di- and triphosphatase activity. Most of these were earlier shown also to be NADH-neotetrazolium reductase active. In addition, two of these antigens exhibited L-leucyl-beta-naphthylamidase activity. As judged from autoradiography these plasma membrane antigens earlier characterized as multienzyme complexes bound [14C]epinephrine, and the same antigens were labelled regardless of whether membranes or membrane extracts were incubated with the radioactive hormone. The specificity of this binding was established in displacement experiments with unlabelled hormones or their analogues. Another hormone-binding antigen, also identified in the plasma membrane extract did not exhibit any known enzyme activity while three antigens with different enzyme activities had no epinephrine-binding capacity. [14C]Epinephrine-labelled plasma membrane extracts were chromatographed on Sepharose 4B and the fractions obtained were analysed in two-dimensional immunoelectrophoresis combined with autoradiography. Nucleoside di- and triphosphatases of high molecular weights (5000000) were associated with L-leucyl-beta-naphthylamidase activity, while no such associations were detected in a lower molecular weight region (70000). Further immunological studies on the various fractionated antigens provided evidence that at least two of them occurred in both low and high molecular weight fractions. Hormone-binding membrane components in varying concentrations were found throughout the eluted extract."} {"id": "PMID:170105", "title": "The order of cyanogen-bromide peptides and location of carbohydrate in the alpha2 chain of guinea-pig skin collagen.", "content": "The alpha2 chain of guinea pig skin collagen contains two additional methionyl residues in comparison with the alpha2 chain of other vertebrate species. The order of the three CNBr peptides unique to the alpha2 chain was established on the basis of the homology of their primary structures to sequences of previously ordered regions in the alpha1 and alpha2 chains of other colagens. The two larger peptides, 4A + 4B, were found to correspond to the region homologous to alpha2-CB4 of other species, while the smaller peptide, 3A, was homologous to the NH2-terminal portion of alpha2-CB3. Thus, the order of the peptides in the alpha2 chain of this collagen is 1-O-4A-4B-2-3A-3B-5. Periodate oxidation and alkaline or acid hydrolysis of the CNBr fragments showed that all of the hydroxlysine-linked carbohydrate in the alpha2 chain was present in alpha2-CB4B. Carbohydrate analyses were most consistent with the existence of single monosaccharide and disaccharide units in this region.", "contents": "The order of cyanogen-bromide peptides and location of carbohydrate in the alpha2 chain of guinea-pig skin collagen. The alpha2 chain of guinea pig skin collagen contains two additional methionyl residues in comparison with the alpha2 chain of other vertebrate species. The order of the three CNBr peptides unique to the alpha2 chain was established on the basis of the homology of their primary structures to sequences of previously ordered regions in the alpha1 and alpha2 chains of other colagens. The two larger peptides, 4A + 4B, were found to correspond to the region homologous to alpha2-CB4 of other species, while the smaller peptide, 3A, was homologous to the NH2-terminal portion of alpha2-CB3. Thus, the order of the peptides in the alpha2 chain of this collagen is 1-O-4A-4B-2-3A-3B-5. Periodate oxidation and alkaline or acid hydrolysis of the CNBr fragments showed that all of the hydroxlysine-linked carbohydrate in the alpha2 chain was present in alpha2-CB4B. Carbohydrate analyses were most consistent with the existence of single monosaccharide and disaccharide units in this region."} {"id": "PMID:170106", "title": "Influence of potassium and calcium ions on the phosphatidylinositol and phosphatidylcholine metabolism in rat fibroblasts after growth stimulation by calf serum.", "content": "In secondary cultures of embryonic rat fibroblasts which were arrested in G1 (G0) by serum depletion and subsequently triggered into the cell cycle by readdition of growth factors isolated from fetal calf serum the influence of the potassium and calcium concentrations in the medium on phosphatidylinositol and phosphatidylcholine metabolism was investigated. The incorporation of inorganic [32P]phosphate into phosphatidylinositol is dependent on the potassium content of the culture medium. The specific activity of 32P in phosphatidylinositol is increased at K+ concentrations between 0.1 and 1 mM. Also calcium (between 0.01 and 2 mM) slightly stimulates phosphatidylinositol metabolism. Also the incorporation of myo-[3H]inositol is increased at potassium concentrations between 0.2 and 1 mM, whereas calcium is slightly inhibitory. The labelling of phosphatidylcholine with either [32P]phosphate or [3H]choline is not dependent on the potassium and calcium concentrations of the culture medium. Moreover, the phospholipid metabolism of permanently growing epithelioid and fibroblastoid cells lines, which were investigated, is considerably less dependent on the K+ and Ca2+ ions.", "contents": "Influence of potassium and calcium ions on the phosphatidylinositol and phosphatidylcholine metabolism in rat fibroblasts after growth stimulation by calf serum. In secondary cultures of embryonic rat fibroblasts which were arrested in G1 (G0) by serum depletion and subsequently triggered into the cell cycle by readdition of growth factors isolated from fetal calf serum the influence of the potassium and calcium concentrations in the medium on phosphatidylinositol and phosphatidylcholine metabolism was investigated. The incorporation of inorganic [32P]phosphate into phosphatidylinositol is dependent on the potassium content of the culture medium. The specific activity of 32P in phosphatidylinositol is increased at K+ concentrations between 0.1 and 1 mM. Also calcium (between 0.01 and 2 mM) slightly stimulates phosphatidylinositol metabolism. Also the incorporation of myo-[3H]inositol is increased at potassium concentrations between 0.2 and 1 mM, whereas calcium is slightly inhibitory. The labelling of phosphatidylcholine with either [32P]phosphate or [3H]choline is not dependent on the potassium and calcium concentrations of the culture medium. Moreover, the phospholipid metabolism of permanently growing epithelioid and fibroblastoid cells lines, which were investigated, is considerably less dependent on the K+ and Ca2+ ions."} {"id": "PMID:170107", "title": "Carcinogen-induced DNA repair in nucleotide-permeable Escherichia coli cells. Induction of DNA repair by the carcinogens methyl and ethyl nitrosourea and methyl methanesulfonate.", "content": "Ether-permeabilized (nucleotide-permeable) cells of Escherichia coli show excision repair of their DNA after having been exposed to the carcinogens N-methyl-N-nitrosourea (MeNOUr), N-ethyl-N-nitrosourea (EtNOUr) and methyl methanesulfonate (MeSO2OMe) which are known to bind covalently to DNA. Defect mutations in genes uvrA, uvrB, uvrC, recA, recB, recC and rep did not inhibit this excision repair. Enzymic activities involved in this repair were identified by measuring size reduction of DNA, DNA degradation to acid-soluble nucleotides and repair polymerization. 1. In permeabilized cells methyl and ethyl nitrosourea induced endonucleolytic cleavage of endogenous DNA, as determined by size reduction of denatured DNA in neutral and alkaline sucrose gradients. An enzymic activity from E. coli K-12 cell extracts was purified (greater than 2000-fold) and was found to cleave preferentially methyl-nitrosourea-treated DNA and to convert the methylated supercoiled DNA duplex (RFI) of phage phiX 174 into the nicked circular form. 2. Degradation of alkylated cellular DNA to acid solubility was diminished in a mutant lacking the 5' leads to 3' exonucleolytic activity of DNA polymerase I but was not affected in a mutant which lacked the DNA polymerizing but retained the 5' leads 3' exonucleolytic activity of DNA polymerase I. 3. An easily measurable effect is carcinogen-induced repair polymerization, making it suitable for detection of covalent binding of carcinogens and potentially carcinogenic compounds.", "contents": "Carcinogen-induced DNA repair in nucleotide-permeable Escherichia coli cells. Induction of DNA repair by the carcinogens methyl and ethyl nitrosourea and methyl methanesulfonate. Ether-permeabilized (nucleotide-permeable) cells of Escherichia coli show excision repair of their DNA after having been exposed to the carcinogens N-methyl-N-nitrosourea (MeNOUr), N-ethyl-N-nitrosourea (EtNOUr) and methyl methanesulfonate (MeSO2OMe) which are known to bind covalently to DNA. Defect mutations in genes uvrA, uvrB, uvrC, recA, recB, recC and rep did not inhibit this excision repair. Enzymic activities involved in this repair were identified by measuring size reduction of DNA, DNA degradation to acid-soluble nucleotides and repair polymerization. 1. In permeabilized cells methyl and ethyl nitrosourea induced endonucleolytic cleavage of endogenous DNA, as determined by size reduction of denatured DNA in neutral and alkaline sucrose gradients. An enzymic activity from E. coli K-12 cell extracts was purified (greater than 2000-fold) and was found to cleave preferentially methyl-nitrosourea-treated DNA and to convert the methylated supercoiled DNA duplex (RFI) of phage phiX 174 into the nicked circular form. 2. Degradation of alkylated cellular DNA to acid solubility was diminished in a mutant lacking the 5' leads to 3' exonucleolytic activity of DNA polymerase I but was not affected in a mutant which lacked the DNA polymerizing but retained the 5' leads 3' exonucleolytic activity of DNA polymerase I. 3. An easily measurable effect is carcinogen-induced repair polymerization, making it suitable for detection of covalent binding of carcinogens and potentially carcinogenic compounds."} {"id": "PMID:170108", "title": "An impaired response of adenylate cyclase to stimulation by epinephrine in adipocyte plasma membranes from genetically obese mice (ob/ob).", "content": "The present studies have established that there is an impaired response to epinephrine of the adenylate system in adipocyte preparations from obese hyperglycemic mice as compared to their thin littermates. In contrast, membrane preparations from both groups of animals were found to exhibit a similar response to fluoride ion. The response of adenylate cyclase to epinephrine was enhanced to a similar extent by increasing the ATP concentration in adipocyte plasma membranes from the two groups of animals. While GTP (0.1 muM) elicited an ATP-like response of similar magnitude in adenylate cyclase activity in both membrane preparations, it did not therefore abolish the impaired response to epinephrine of adenylate cyclase activity in membranes of obese mice. The response of adenylate cyclase activity to (--)-epinephrine in membrane preparations from obese mice progressively diminished with the age of these animals. In contrast, the concentration of (--)-epinephrine required for half-maximal stimulation of adenylate cyclase was similar and remained unchanged with the age for both membrane preparations. These data suggest that a perturbation may occur in the coupling step between the hormone receptor and the catalytic site of the adenylate cyclase system in obese mice. While a 15-day restrictive diet or a 72-h period of fasting was found to normalize the hyperinsulinemia of obese animals, neither affected the response of adenylate cyclase to epinephrine in preparations of adipocyte membranes from these mice. These results suggest that the observed defect in the response of plasma membrane adenylate cyclase activity to epinephrine in obese mice does not result from their hyperinsulinism.", "contents": "An impaired response of adenylate cyclase to stimulation by epinephrine in adipocyte plasma membranes from genetically obese mice (ob/ob). The present studies have established that there is an impaired response to epinephrine of the adenylate system in adipocyte preparations from obese hyperglycemic mice as compared to their thin littermates. In contrast, membrane preparations from both groups of animals were found to exhibit a similar response to fluoride ion. The response of adenylate cyclase to epinephrine was enhanced to a similar extent by increasing the ATP concentration in adipocyte plasma membranes from the two groups of animals. While GTP (0.1 muM) elicited an ATP-like response of similar magnitude in adenylate cyclase activity in both membrane preparations, it did not therefore abolish the impaired response to epinephrine of adenylate cyclase activity in membranes of obese mice. The response of adenylate cyclase activity to (--)-epinephrine in membrane preparations from obese mice progressively diminished with the age of these animals. In contrast, the concentration of (--)-epinephrine required for half-maximal stimulation of adenylate cyclase was similar and remained unchanged with the age for both membrane preparations. These data suggest that a perturbation may occur in the coupling step between the hormone receptor and the catalytic site of the adenylate cyclase system in obese mice. While a 15-day restrictive diet or a 72-h period of fasting was found to normalize the hyperinsulinemia of obese animals, neither affected the response of adenylate cyclase to epinephrine in preparations of adipocyte membranes from these mice. These results suggest that the observed defect in the response of plasma membrane adenylate cyclase activity to epinephrine in obese mice does not result from their hyperinsulinism."} {"id": "PMID:170109", "title": "Human prolyl hydroxylase. Purification, partial characterization and preparation of antiserum to the enzyme.", "content": "Prolyl hydroxylase was purified from human foetal skin and from a mixture of human foetal tissues by the affinity chromatography procedure using poly(L-proline). The enzyme from both sources was pure, when examined by polyacrylamide gel electrophoresis, as a native protein or in the presence of sodium dodecylsulphate, and enzyme activity recovery varied from 38% to 70% with seven enzyme preparations. The enzyme synthesized from 61.0 mumol to 82.7 mumol hydroxyproline mg protein-1 h-1 degrees C with a saturating concentration of (Pro-Pro-Gly)5 as substrate. The molecular weight of the enzyme was identical with that of the chick prolyl hydroxylase when studied by gel filtration, and the molecular weights of the subunits of the enzyme were about 61000 and 64000 as determined by sodium dodecylsulphate-polyacrylamide gel electrophoresis. The amino acid composition of the human enzyme was very similar to that of the chick prolyl hydroxylase. Antisera to human and chick prolyl hydroxylases were prepared in rabbits. A single precipitin line was seen between the antiserum to human prolyl hydroxylase and the human enzyme in double immunodiffusion, and no cross-reactivity was detected between the human chick enzymes by this technique. However, a distinct cross-reactivity was observed between the human and chick enzymes in inhibition experiments.", "contents": "Human prolyl hydroxylase. Purification, partial characterization and preparation of antiserum to the enzyme. Prolyl hydroxylase was purified from human foetal skin and from a mixture of human foetal tissues by the affinity chromatography procedure using poly(L-proline). The enzyme from both sources was pure, when examined by polyacrylamide gel electrophoresis, as a native protein or in the presence of sodium dodecylsulphate, and enzyme activity recovery varied from 38% to 70% with seven enzyme preparations. The enzyme synthesized from 61.0 mumol to 82.7 mumol hydroxyproline mg protein-1 h-1 degrees C with a saturating concentration of (Pro-Pro-Gly)5 as substrate. The molecular weight of the enzyme was identical with that of the chick prolyl hydroxylase when studied by gel filtration, and the molecular weights of the subunits of the enzyme were about 61000 and 64000 as determined by sodium dodecylsulphate-polyacrylamide gel electrophoresis. The amino acid composition of the human enzyme was very similar to that of the chick prolyl hydroxylase. Antisera to human and chick prolyl hydroxylases were prepared in rabbits. A single precipitin line was seen between the antiserum to human prolyl hydroxylase and the human enzyme in double immunodiffusion, and no cross-reactivity was detected between the human chick enzymes by this technique. However, a distinct cross-reactivity was observed between the human and chick enzymes in inhibition experiments."} {"id": "PMID:170110", "title": "Synthetic inhibitors of adenylate kinases in the assays for ATPases and phosphokinases.", "content": "1. Procedures are given for the syntheses of alpha,omega-dinucleoside 5'-polyphosphates as inhibitors of adenylate kinases. The following order for the ability of inhibiting pig muscle adenylate kinase was observed: Ap5A greater than 1:N6-etheno-Ap5A greater than Ap6A greater than Gp5A greater than Ap4A greater than Up5A. The synthesis of adenosine tetraphosphate, the starting material for Ap5A, is also described. 2. One molecule of pig muscle adenylate kinase binds one molecule of Ap5A. The difference spectrum of Ap5A-adenylate kinase with its maximum of 5050 M-1 - cm-1 at 271 nm, as well as the fluorescence properties of 1:N6-etheno-Ap5A can be used for kinetic and binding studies. 3. The specific binding of the negatively charged Ap5A was exploited in the preparation of human muscle adenylate kinase. The enzyme was purified to homogeneity with an overall yield of 65%, the absolute value being 70 mg per kg of muscle. 4. The effect of Ap5A on adenylate kinase in extracts of various cells and cell organelles was tested. A ratio of 1:50 (mol/mol) for Ap5A to other nucleotides was used for suppressing the adenylate kinase activity in extracts of mammalian and insect skeletal muscel, of human erythrocytes and of Staphylococcus aureus. A ratio of 1:5 was found to be necessary for the adenylate kinase from tobacco leaves and spinach chloroplasts, and a ratio of 2:1 was needed for suppressing the adenylate kinase from bovine liver mitochondria, human kidney homogenate and from Escherichia coli. Ap5A appears not to be metabolized in any of the above extracts. These results indicate that Ap5A can be used for evaluating the contribution of adenylate kinase to the production of ATP fro ADP in energy-transducing systems. 5. Contaminating adenylate kinase can be inhibited by a concentration of Ap5A which does not interfere in the study of many (phospho)kinases and ATPases. The applications of Ap5A in the assay for nucleoside diphosphokinase and in the study of mechanical and biochemical properties of contractile proteins are representative examples. The use of Ap5A makes it possible to study the effect of ADP per se in such systems. 6. Sepharose-bound Ap5A was used for removing traces of adenylate kinase from samples of myosin and creatine kinase. 7. In the presence of Ap5A the activity of creatine kinase was measured in hemolytic serum of venous blood, in plasma of capillary blood and in samples of whole blood after complete hemolysis had been induced. The clinical significance of these findings are shown for cases of myocardial infarction and muscular dystrophy.", "contents": "Synthetic inhibitors of adenylate kinases in the assays for ATPases and phosphokinases. 1. Procedures are given for the syntheses of alpha,omega-dinucleoside 5'-polyphosphates as inhibitors of adenylate kinases. The following order for the ability of inhibiting pig muscle adenylate kinase was observed: Ap5A greater than 1:N6-etheno-Ap5A greater than Ap6A greater than Gp5A greater than Ap4A greater than Up5A. The synthesis of adenosine tetraphosphate, the starting material for Ap5A, is also described. 2. One molecule of pig muscle adenylate kinase binds one molecule of Ap5A. The difference spectrum of Ap5A-adenylate kinase with its maximum of 5050 M-1 - cm-1 at 271 nm, as well as the fluorescence properties of 1:N6-etheno-Ap5A can be used for kinetic and binding studies. 3. The specific binding of the negatively charged Ap5A was exploited in the preparation of human muscle adenylate kinase. The enzyme was purified to homogeneity with an overall yield of 65%, the absolute value being 70 mg per kg of muscle. 4. The effect of Ap5A on adenylate kinase in extracts of various cells and cell organelles was tested. A ratio of 1:50 (mol/mol) for Ap5A to other nucleotides was used for suppressing the adenylate kinase activity in extracts of mammalian and insect skeletal muscel, of human erythrocytes and of Staphylococcus aureus. A ratio of 1:5 was found to be necessary for the adenylate kinase from tobacco leaves and spinach chloroplasts, and a ratio of 2:1 was needed for suppressing the adenylate kinase from bovine liver mitochondria, human kidney homogenate and from Escherichia coli. Ap5A appears not to be metabolized in any of the above extracts. These results indicate that Ap5A can be used for evaluating the contribution of adenylate kinase to the production of ATP fro ADP in energy-transducing systems. 5. Contaminating adenylate kinase can be inhibited by a concentration of Ap5A which does not interfere in the study of many (phospho)kinases and ATPases. The applications of Ap5A in the assay for nucleoside diphosphokinase and in the study of mechanical and biochemical properties of contractile proteins are representative examples. The use of Ap5A makes it possible to study the effect of ADP per se in such systems. 6. Sepharose-bound Ap5A was used for removing traces of adenylate kinase from samples of myosin and creatine kinase. 7. In the presence of Ap5A the activity of creatine kinase was measured in hemolytic serum of venous blood, in plasma of capillary blood and in samples of whole blood after complete hemolysis had been induced. The clinical significance of these findings are shown for cases of myocardial infarction and muscular dystrophy."} {"id": "PMID:170111", "title": "Evidence for the amino-acid sequence of Crithidia fasciculata Cytochrome c555.", "content": "Evidence is presented which indicates that the amino acid sequence of cytochrome c555 from Crithidia fasciculata differs at sixteen positions from that of cytochrome c557 from Crithidia oncopelti. 101 residues were identified by dansyl-Edman degradation, carboxypeptidase digestion or considerations of the specificity of trypsin and of these, thirteen were found to be different from C. oncopelti cytochrome c557. The remaining 11 residues found in the amino acid composition of the trypic peptides were aligned on the basis of homology with cytochrome c557 and three further differences are proposed. The total of sixteen amino acid differences is surprising in view of the morphological and biochemical similarities of these organisms, and illustrates the problem of taxonomy of morphologically simple organisms. In both cytochromes only one cysteine residue is involved in the attachment of the protein to the prosthetic group.", "contents": "Evidence for the amino-acid sequence of Crithidia fasciculata Cytochrome c555. Evidence is presented which indicates that the amino acid sequence of cytochrome c555 from Crithidia fasciculata differs at sixteen positions from that of cytochrome c557 from Crithidia oncopelti. 101 residues were identified by dansyl-Edman degradation, carboxypeptidase digestion or considerations of the specificity of trypsin and of these, thirteen were found to be different from C. oncopelti cytochrome c557. The remaining 11 residues found in the amino acid composition of the trypic peptides were aligned on the basis of homology with cytochrome c557 and three further differences are proposed. The total of sixteen amino acid differences is surprising in view of the morphological and biochemical similarities of these organisms, and illustrates the problem of taxonomy of morphologically simple organisms. In both cytochromes only one cysteine residue is involved in the attachment of the protein to the prosthetic group."} {"id": "PMID:170112", "title": "Proton nuclear-magnetic-resonance study of low-spin ferriprotoporphyrin(IX) dimethyl ester.", "content": "Proton nuclear magnetic resonance shifts, spin-lattice and spin-spin relaxation times have been measured of low-spin bis-pyridine ferriprotoporphyrin(IX) dimethyl ester in chloroform. From the relaxation behavior the hyperfine coupling constant has been obtained and the contact term of the chemical shift was calculated. Deviations between measured and calculated chemical shifts may be attributed to second-order Zeeman interactions. The geometry of pyridine coordinated to the fifth and sixth position of ferriprotoporphyrin(IX) dimethyl ester was estimated from measured relaxation rates. From the non-exponential decay of the Mz magnetization a mean lifetime of taub = 50 ms for pyridine attached to low-spin ferriprotoporphyrin(IX) dimethyl ester was found at 253 K.", "contents": "Proton nuclear-magnetic-resonance study of low-spin ferriprotoporphyrin(IX) dimethyl ester. Proton nuclear magnetic resonance shifts, spin-lattice and spin-spin relaxation times have been measured of low-spin bis-pyridine ferriprotoporphyrin(IX) dimethyl ester in chloroform. From the relaxation behavior the hyperfine coupling constant has been obtained and the contact term of the chemical shift was calculated. Deviations between measured and calculated chemical shifts may be attributed to second-order Zeeman interactions. The geometry of pyridine coordinated to the fifth and sixth position of ferriprotoporphyrin(IX) dimethyl ester was estimated from measured relaxation rates. From the non-exponential decay of the Mz magnetization a mean lifetime of taub = 50 ms for pyridine attached to low-spin ferriprotoporphyrin(IX) dimethyl ester was found at 253 K."} {"id": "PMID:170113", "title": "Sturgeon glyceraldehyde-3-phosphate dehydrogenase.", "content": "The formation of binary complexes between sturgeon apoglyceralddhyde-3-phosphate dehydrogenase, coenzymes (NAD+ and NADH) and substrates (phosphate, glyceraldehyde 3-phosphate and 1,3-bisphosphoglycerate) has been studied spectrophotometrically and spectrofluorometrica-ly. Coenzyme binding to the apoenzyme can be characterized by several distinct spectroscopic properties: (a) the low intensity absorption band centered at 360 nm which is specific of NAD+ binding (Racker band); (b) the quenching of the enzyme fluorescence upon coenzyme binding; (c) the quenching of the fluorescence of the dihydronicotinamide moiety of the reduced coenzyme (NADH); (D) the hypochromicity and the red shift of the absorption band of NADH centered at 338 nm; (e) the coenzyme-induced difference spectra in the enzyme absorbance region. The analysis of these spectroscopic properties shows that up to four molecules of coenzyme are bound per molecule of enzyme tetramer. In every case, each successively bound coenzyme molecule contributes identically to the total observed change. Two classes of binding sites are apparent at lower temperatures for NAD+ Binding. Similarly, the binding of NADH seems to involve two distinct classes of binding sites. The excitation fluorescence spectra of NADH in the binary complex shows a component centered at 260 nm as in aqueous solution. This is consistent with a \"folded\" conformation of the reduced coenzyme in the binary complex, contradictory to crystallographic results. Possible reasons for this discrepancy are discussed. Binding of phosphorylated substrates and orthophosphate induce similar difference spectra in the enzyme absorbance region. No anticooperativity is detectable in the binding of glyceraldehyde 3-phosphate. These results are discussed in light of recent crystallographic studies on glyceraldehyde-3-phosphate dehydrogenases.", "contents": "Sturgeon glyceraldehyde-3-phosphate dehydrogenase. The formation of binary complexes between sturgeon apoglyceralddhyde-3-phosphate dehydrogenase, coenzymes (NAD+ and NADH) and substrates (phosphate, glyceraldehyde 3-phosphate and 1,3-bisphosphoglycerate) has been studied spectrophotometrically and spectrofluorometrica-ly. Coenzyme binding to the apoenzyme can be characterized by several distinct spectroscopic properties: (a) the low intensity absorption band centered at 360 nm which is specific of NAD+ binding (Racker band); (b) the quenching of the enzyme fluorescence upon coenzyme binding; (c) the quenching of the fluorescence of the dihydronicotinamide moiety of the reduced coenzyme (NADH); (D) the hypochromicity and the red shift of the absorption band of NADH centered at 338 nm; (e) the coenzyme-induced difference spectra in the enzyme absorbance region. The analysis of these spectroscopic properties shows that up to four molecules of coenzyme are bound per molecule of enzyme tetramer. In every case, each successively bound coenzyme molecule contributes identically to the total observed change. Two classes of binding sites are apparent at lower temperatures for NAD+ Binding. Similarly, the binding of NADH seems to involve two distinct classes of binding sites. The excitation fluorescence spectra of NADH in the binary complex shows a component centered at 260 nm as in aqueous solution. This is consistent with a \"folded\" conformation of the reduced coenzyme in the binary complex, contradictory to crystallographic results. Possible reasons for this discrepancy are discussed. Binding of phosphorylated substrates and orthophosphate induce similar difference spectra in the enzyme absorbance region. No anticooperativity is detectable in the binding of glyceraldehyde 3-phosphate. These results are discussed in light of recent crystallographic studies on glyceraldehyde-3-phosphate dehydrogenases."} {"id": "PMID:170114", "title": "Preparation of an alcohol-dehydrogenase--NAD(H)--sepharose complex showing no requirement of soluble coenzyme for its activity.", "content": "1. Horse liver alcohol dehydrogenase and an NADH analogue, N6-[(6-aminohexyl)carbamoylmethyl]-NADH, have been co-immobilized to Sepharose 4B under conditions permitting binary complex formation between the enzyme and the cofactor. 2. The enzyme-coenzyme-matrix preparations were assayed with a coupled oxidoreduction reaction and showed activities, prior to addition of coenzyme, that were up to 40% of that obtained in excess of free coenzyme. 3. A molar ratio of 1:1 between the amount of bound enzyme was sufficient to obtain high activities in the absence of free coenzyme. 4. The highest recycling rate obtained for the immobilized nucleotide was 3400 cycles per hour. 5. Both thermal and storage stability of alcohol dehydrogenase was increased when the enzyme was co-immobilized with the NADH analogue. 6. The efficiency of the immobilized preparations (measured as product formation per minute and per assay volume) was higher (1.4 to 5 times in our assays) than the corresponding systems of free enzyme (in total enzyme units) and nucleotide in an identical assay volume.", "contents": "Preparation of an alcohol-dehydrogenase--NAD(H)--sepharose complex showing no requirement of soluble coenzyme for its activity. 1. Horse liver alcohol dehydrogenase and an NADH analogue, N6-[(6-aminohexyl)carbamoylmethyl]-NADH, have been co-immobilized to Sepharose 4B under conditions permitting binary complex formation between the enzyme and the cofactor. 2. The enzyme-coenzyme-matrix preparations were assayed with a coupled oxidoreduction reaction and showed activities, prior to addition of coenzyme, that were up to 40% of that obtained in excess of free coenzyme. 3. A molar ratio of 1:1 between the amount of bound enzyme was sufficient to obtain high activities in the absence of free coenzyme. 4. The highest recycling rate obtained for the immobilized nucleotide was 3400 cycles per hour. 5. Both thermal and storage stability of alcohol dehydrogenase was increased when the enzyme was co-immobilized with the NADH analogue. 6. The efficiency of the immobilized preparations (measured as product formation per minute and per assay volume) was higher (1.4 to 5 times in our assays) than the corresponding systems of free enzyme (in total enzyme units) and nucleotide in an identical assay volume."} {"id": "PMID:170115", "title": "Oestrogen receptors in chick oviduct. Characterization and subcellular distribution.", "content": "Macromolecular components with properties of oestrogen receptors have been identified in the 0.5 M KCl nuclear soluble, the nuclear insoluble and the cytosol fractions of laying hen and immature (2--4 weeks, untreated by hormone) chicken oviduct. 7n the 0.5 M KCl extract of laying hen oviduct nuclei, a receptor, of protein nature according to the effects of enzymic treatments, has been identified. It exhibits high affinity for oestradiol with an apparent equilibrium association constant KA = 4 - 109 M-1 at 4 degrees C. The binding of [3H] oestradiol is abolished by 1 muM oestriol, oestrone and diethylstilboestrol, but not by the same concentration of progesterone, testosterone, and cortisol. Sucrose gradient ultracentrifugation studies in the presence of 0.5 M KCl indicate a sedimentation coefficient of 4.3 S, and there is partial aggregation in low-ionic-strength medium. The estimated number of binding sites per nucleus is about 5000, as calculated from DNA content of chick diploid genome. Most of the binding sites were found to be occupied by endogenous oestrogen(s). Oestradiol dissociates from the receptor according to an apparent two-step mechanism. The half-life time for the faster dissociation step is 18 h at 0 degrees C, 25 min at 20 degrees C and 10 min at 30 degrees C, and for the slower one is 180 h, 115 min and 60 min, respectively. In the 0.5 M KCl extract of immature chicken oviduct nuclei, there are approximately 500 receptor sites per nucleus; their affinity for oestradiol is the same as in the case of laying hen soluble nuclear receptor. After repeated extractions of nuclei with 0.5 M KCl medium, a substantial quantity of oestrogen binding sites remains in the residual fraction. Binding characteristics of this insoluble nuclear receptor resemble those of the soluble nuclear receptor: high affinity for oestradiol (KA = 7 - 10(8) M-1 at 37 degrees C) and specificity for oestrogens. The estimated number of binding sites are approximately 2000/cell for laying hen, and approximately 1000/cell for immature chicken. In the high-speed supernatant fraction of laying hen oviduct homogenates, an oestrogen receptor is also present, but its concentration is low (less than or equal to 100 sites/cell) and at the limits of sensitivity of the methods used. In the cytosol of immature chicken oviduct, there are approximately 2500 oestradiol receptor sites per cell.", "contents": "Oestrogen receptors in chick oviduct. Characterization and subcellular distribution. Macromolecular components with properties of oestrogen receptors have been identified in the 0.5 M KCl nuclear soluble, the nuclear insoluble and the cytosol fractions of laying hen and immature (2--4 weeks, untreated by hormone) chicken oviduct. 7n the 0.5 M KCl extract of laying hen oviduct nuclei, a receptor, of protein nature according to the effects of enzymic treatments, has been identified. It exhibits high affinity for oestradiol with an apparent equilibrium association constant KA = 4 - 109 M-1 at 4 degrees C. The binding of [3H] oestradiol is abolished by 1 muM oestriol, oestrone and diethylstilboestrol, but not by the same concentration of progesterone, testosterone, and cortisol. Sucrose gradient ultracentrifugation studies in the presence of 0.5 M KCl indicate a sedimentation coefficient of 4.3 S, and there is partial aggregation in low-ionic-strength medium. The estimated number of binding sites per nucleus is about 5000, as calculated from DNA content of chick diploid genome. Most of the binding sites were found to be occupied by endogenous oestrogen(s). Oestradiol dissociates from the receptor according to an apparent two-step mechanism. The half-life time for the faster dissociation step is 18 h at 0 degrees C, 25 min at 20 degrees C and 10 min at 30 degrees C, and for the slower one is 180 h, 115 min and 60 min, respectively. In the 0.5 M KCl extract of immature chicken oviduct nuclei, there are approximately 500 receptor sites per nucleus; their affinity for oestradiol is the same as in the case of laying hen soluble nuclear receptor. After repeated extractions of nuclei with 0.5 M KCl medium, a substantial quantity of oestrogen binding sites remains in the residual fraction. Binding characteristics of this insoluble nuclear receptor resemble those of the soluble nuclear receptor: high affinity for oestradiol (KA = 7 - 10(8) M-1 at 37 degrees C) and specificity for oestrogens. The estimated number of binding sites are approximately 2000/cell for laying hen, and approximately 1000/cell for immature chicken. In the high-speed supernatant fraction of laying hen oviduct homogenates, an oestrogen receptor is also present, but its concentration is low (less than or equal to 100 sites/cell) and at the limits of sensitivity of the methods used. In the cytosol of immature chicken oviduct, there are approximately 2500 oestradiol receptor sites per cell."} {"id": "PMID:170119", "title": "Conversion of type III hyperlipoproteinaemia to type IV hyperlipoproteinaemia by a fat-free, carbohydrate rich diet.", "content": "Hyperlipoproteinaemia type III has been considered a clear cut clinical entity characterized by the presence of cholesterol rich \"floating\" beta very low density lipoproteins (VLDL) after ultracentrifugation. Carbohydrate inducibility is pronounced in type III. This study was undertaken to elucidate the effect of a high carbohydrate diet in type III as an effort to clarify a suggested association between type III and IV hyperlipoproteinaemia. On an isocaloric fat free carbohydrate rich diet the lipoprotein pattern changed as the VLDL triglycerides increased 31 per cent on average and LDL and HDL cholesterol decreased by 40 and 22 per cent. The high ratio cholesterol/triglycerides in VLDL was normalized. The lipoprotein levels in serum after carbohydrate induction showed all characteristics of a type IV with high VLDL triglycerides, normal cholesterol/triglyceride ratio in VLDL, subnormal cholesterol levels in LDL and HDL with changed relation between LDL1 and LDL2. On electrophoresis the floating beta band disappeared. It is probable that depending on the nutritional situation, the metabolic defect in type III may be expressed either as a type III or a type IV. An explanation of the effects of the carbohydrate rich diet on the lipoprotein pattern is suggested.", "contents": "Conversion of type III hyperlipoproteinaemia to type IV hyperlipoproteinaemia by a fat-free, carbohydrate rich diet. Hyperlipoproteinaemia type III has been considered a clear cut clinical entity characterized by the presence of cholesterol rich \"floating\" beta very low density lipoproteins (VLDL) after ultracentrifugation. Carbohydrate inducibility is pronounced in type III. This study was undertaken to elucidate the effect of a high carbohydrate diet in type III as an effort to clarify a suggested association between type III and IV hyperlipoproteinaemia. On an isocaloric fat free carbohydrate rich diet the lipoprotein pattern changed as the VLDL triglycerides increased 31 per cent on average and LDL and HDL cholesterol decreased by 40 and 22 per cent. The high ratio cholesterol/triglycerides in VLDL was normalized. The lipoprotein levels in serum after carbohydrate induction showed all characteristics of a type IV with high VLDL triglycerides, normal cholesterol/triglyceride ratio in VLDL, subnormal cholesterol levels in LDL and HDL with changed relation between LDL1 and LDL2. On electrophoresis the floating beta band disappeared. It is probable that depending on the nutritional situation, the metabolic defect in type III may be expressed either as a type III or a type IV. An explanation of the effects of the carbohydrate rich diet on the lipoprotein pattern is suggested."} {"id": "PMID:170120", "title": "Influence of peptides on reduced response of rats to electric footshock after acute administration of morphine.", "content": "Acute treatment of rats with morphine (10 mg/kg) resulted in a marked reduction of motor response to inescapable electric footshock (EFS). Nalorphine (2mg/kg) antagonized this action of morphine. Pretreatment with synthetic ACTH 1-24 (10 IU) 60 min prior to testing also inhibited this morphine-induced reduction, whereas other ACTH-like peptides, lacking corticotrophic activity, were ineffective. ACTH 1-24 had no effect on the response of adrenalectomized rats to EFS after morphine. In intact rats dexamethasone pretreatment 4 hr prior to testing also antagonized the action of morphine on EFS. Taken together these findings suggest that ACTH 1-24 interferes with the antinociceptive action of morphine and that the integrity of the adrenal is essential for demonstration of this antagonism.", "contents": "Influence of peptides on reduced response of rats to electric footshock after acute administration of morphine. Acute treatment of rats with morphine (10 mg/kg) resulted in a marked reduction of motor response to inescapable electric footshock (EFS). Nalorphine (2mg/kg) antagonized this action of morphine. Pretreatment with synthetic ACTH 1-24 (10 IU) 60 min prior to testing also inhibited this morphine-induced reduction, whereas other ACTH-like peptides, lacking corticotrophic activity, were ineffective. ACTH 1-24 had no effect on the response of adrenalectomized rats to EFS after morphine. In intact rats dexamethasone pretreatment 4 hr prior to testing also antagonized the action of morphine on EFS. Taken together these findings suggest that ACTH 1-24 interferes with the antinociceptive action of morphine and that the integrity of the adrenal is essential for demonstration of this antagonism."} {"id": "PMID:170123", "title": "Influence of agents that act on DNA and RNA synthesis on the activity of poly(ADP-Rib) polymerase.", "content": "The activity of poly(ADP-Rib) polymerase is enhanced in the presence of spermine and spermidine. Among the adenosine-like antibiotics tested, only formycin B and showdomycin cause an inhibition of the enzyme, which is competitive to NAD. The activity of poly(ADP-Rib) polymerase is not reduced by rifamycin, alpha-amanitin and 2-phenylethanol.", "contents": "Influence of agents that act on DNA and RNA synthesis on the activity of poly(ADP-Rib) polymerase. The activity of poly(ADP-Rib) polymerase is enhanced in the presence of spermine and spermidine. Among the adenosine-like antibiotics tested, only formycin B and showdomycin cause an inhibition of the enzyme, which is competitive to NAD. The activity of poly(ADP-Rib) polymerase is not reduced by rifamycin, alpha-amanitin and 2-phenylethanol."} {"id": "PMID:170124", "title": "Mechanism of urea nitrogen binding by proposed oxidized starch gastrointestinal absorbents.", "content": "By use of 14-C label it was demonstrated that apparent binding of urea N to polyaldehyde starch was probably preceeded by hydrolysis to ammonium ion. Thus direct urea binding was not the mechanism through which ingested polyaldehyde starch might increase fecal N excretion in uremic patients.", "contents": "Mechanism of urea nitrogen binding by proposed oxidized starch gastrointestinal absorbents. By use of 14-C label it was demonstrated that apparent binding of urea N to polyaldehyde starch was probably preceeded by hydrolysis to ammonium ion. Thus direct urea binding was not the mechanism through which ingested polyaldehyde starch might increase fecal N excretion in uremic patients."} {"id": "PMID:170125", "title": "Membrane fractions of rabbit granulocytes. 1. The presence of ouabain-sensitive ATPase and the electrophoretic patterns.", "content": "In one or two membrane fractions isolated from the homogenate of casein-induced rabbit granulocytes ouabain-sensitive ATPase activity was found definitely. Electrophoretic patterns of these membrane fractions showed no significant differences in staining for carbohydrate and protein.", "contents": "Membrane fractions of rabbit granulocytes. 1. The presence of ouabain-sensitive ATPase and the electrophoretic patterns. In one or two membrane fractions isolated from the homogenate of casein-induced rabbit granulocytes ouabain-sensitive ATPase activity was found definitely. Electrophoretic patterns of these membrane fractions showed no significant differences in staining for carbohydrate and protein."} {"id": "PMID:170126", "title": "APUD characteristics and immunocytochemistry of avian pituitary corticotrophs.", "content": "L-DOPA is taken up and decarboxylated by cells in the avian adenohypophysis, which are situated largely in the cephalic lobe. These APUD cells have been shown by sequential formaldehyde-induced and immunofluorescence to be corticotrophs and the relationship between the two procedures has been found to have a reciprocal quality.", "contents": "APUD characteristics and immunocytochemistry of avian pituitary corticotrophs. L-DOPA is taken up and decarboxylated by cells in the avian adenohypophysis, which are situated largely in the cephalic lobe. These APUD cells have been shown by sequential formaldehyde-induced and immunofluorescence to be corticotrophs and the relationship between the two procedures has been found to have a reciprocal quality."} {"id": "PMID:170127", "title": "Effect of insulin on the glucose uptake of protozoa.", "content": "Insulin stimulates the glucose uptake of Tetrahymena pyriformis. This shows the presence of insulin receptors in Tetrahymena, consequently receptors may be present in a level of phylogenesis, where the natural contact between the given hormone and the cell is unnecessary and impossible.", "contents": "Effect of insulin on the glucose uptake of protozoa. Insulin stimulates the glucose uptake of Tetrahymena pyriformis. This shows the presence of insulin receptors in Tetrahymena, consequently receptors may be present in a level of phylogenesis, where the natural contact between the given hormone and the cell is unnecessary and impossible."} {"id": "PMID:170128", "title": "Effects of hypophysectomy, bilateral adrenalectomy and hormone replacement therapy upon organ monoamine oxidase activity.", "content": "Changes in MAO activity after hypophysectomy (HX) are not due to adrenal insufficiency. ACTH failed to reverse the effects of HX and enhanced the depression of cardiac and spleenic MAO. The data suggests both facilitatory and inhibitory effects of pituitary hormones on MAO activity.", "contents": "Effects of hypophysectomy, bilateral adrenalectomy and hormone replacement therapy upon organ monoamine oxidase activity. Changes in MAO activity after hypophysectomy (HX) are not due to adrenal insufficiency. ACTH failed to reverse the effects of HX and enhanced the depression of cardiac and spleenic MAO. The data suggests both facilitatory and inhibitory effects of pituitary hormones on MAO activity."} {"id": "PMID:170138", "title": "A biomedical information source: the National Clearinghouse for Alcohol Information.", "content": "The National Clearinghouse for Alcohol Information (NCALI) is an information resource developed by the National Institute on Alcohol Abuse and Alcoholism of the U.S. Department of Health, Education, and Welfare. It provides numerous alcohol-related information services to professionals in a wide spectrum of biomedical and other disciplines, services that are designed to aid information users in the discrimination and selection of useful literature from the volumes of available information. One such service will provide the biomedical professional, working in an alcohol-related field, with announcements of recent information in categories that he selects from 110 possible fields of interest. Another information service is the quality evaluation of technical documents. The quality evaluation system, which is under continuing development and refinement, serves the literature user by providing a literature quality prescreening process designed to aid users in their literature review and monitoring activities. Additional information services provided by the clearinghouse include Grouped Interest Guides, Subject Area Bibliographies, a quarterly magazine and a periodic general interest information service, and a wide range of special publications. Reference services provide a suitable depth of response to information requests through services that range from assemblages of standard information materials, such as pamphlets and similar publications, to automated data base searches for more technically oriented information requests.", "contents": "A biomedical information source: the National Clearinghouse for Alcohol Information. The National Clearinghouse for Alcohol Information (NCALI) is an information resource developed by the National Institute on Alcohol Abuse and Alcoholism of the U.S. Department of Health, Education, and Welfare. It provides numerous alcohol-related information services to professionals in a wide spectrum of biomedical and other disciplines, services that are designed to aid information users in the discrimination and selection of useful literature from the volumes of available information. One such service will provide the biomedical professional, working in an alcohol-related field, with announcements of recent information in categories that he selects from 110 possible fields of interest. Another information service is the quality evaluation of technical documents. The quality evaluation system, which is under continuing development and refinement, serves the literature user by providing a literature quality prescreening process designed to aid users in their literature review and monitoring activities. Additional information services provided by the clearinghouse include Grouped Interest Guides, Subject Area Bibliographies, a quarterly magazine and a periodic general interest information service, and a wide range of special publications. Reference services provide a suitable depth of response to information requests through services that range from assemblages of standard information materials, such as pamphlets and similar publications, to automated data base searches for more technically oriented information requests."} {"id": "PMID:170141", "title": "[Determination of conjugated and free estrogen in male plasma (authors transl)].", "content": "Radioimmunoassay for conjugated and free estrone (E1), estradiol-17beta(E2) and estriol (E3) in male plasma was investigated, while no precise determination of conjugated estrogen in male plasma had been established. Each tritiated estrogen glucuronides for determining the recovery was added to 3 ml of plasma samples. These plasma samples were extracted with acetone, hydrolyzed with 15 vol% HCl at 100 degrees C for 60 minutes, and resulting free estrogens were extracted with ether. These extracts were washed with 1% NaOH and 1% NaHCO3, and applied to microcolumn of Sephadex LH-20. Then they were determined by the radioimmunoassay as the same method of evaluation for free estrogen. Each mean values of plasma free and conjugated estrogen in 10 normal adult males was as follows: 36.0 +/- 9.81 pg/ml(free E1), 29.5 +/- 11.0 pg/ml(free E2), 1.80 +/- 1.27 pg/ml (free E3), 31.0 +/- 12.6 pg/ml (conjugated E1), 36.0 +/- 14.2 pg/ml (conjugated E2), 30.6 +/- 8.35 pg/ml (conjugated E3). Conjugated estrogen to free estrogen ratio was 1.45.", "contents": "[Determination of conjugated and free estrogen in male plasma (authors transl)]. Radioimmunoassay for conjugated and free estrone (E1), estradiol-17beta(E2) and estriol (E3) in male plasma was investigated, while no precise determination of conjugated estrogen in male plasma had been established. Each tritiated estrogen glucuronides for determining the recovery was added to 3 ml of plasma samples. These plasma samples were extracted with acetone, hydrolyzed with 15 vol% HCl at 100 degrees C for 60 minutes, and resulting free estrogens were extracted with ether. These extracts were washed with 1% NaOH and 1% NaHCO3, and applied to microcolumn of Sephadex LH-20. Then they were determined by the radioimmunoassay as the same method of evaluation for free estrogen. Each mean values of plasma free and conjugated estrogen in 10 normal adult males was as follows: 36.0 +/- 9.81 pg/ml(free E1), 29.5 +/- 11.0 pg/ml(free E2), 1.80 +/- 1.27 pg/ml (free E3), 31.0 +/- 12.6 pg/ml (conjugated E1), 36.0 +/- 14.2 pg/ml (conjugated E2), 30.6 +/- 8.35 pg/ml (conjugated E3). Conjugated estrogen to free estrogen ratio was 1.45."} {"id": "PMID:170142", "title": "[Steroidogenesis in isolated adrenal cells of rat. -Effects of cyanoketone on pregnenolone and corticosterone production- (author's transl)].", "content": "In order to study the effect of cyanoketone on steroidogenesis of rat adrenal, the assay technique for corticosteroids released into the incubated media of the rat adrenal cells treated with collagenase was basically investigated. Corticosterone was measured by fluorometric method and pregnenolone by radioimmunoassay. Reliability of radioimmunoassay was satisfactory. About 400,000 cells were obtained from one adrenal gland of male or female rats and sex-dependent difference in pregnenolone and corticosterone production in response to ACTH was not found. Net corticosterone production by isolated adrenal cells was related to the log of the concentration of ACTH by a sigmoid curve over the range 1 to 1000 muU/ml. The half-maximum response was observed at an ACTH concentration of 10 muU/ml, and maximum corticosterone production responding to ACTH (100-1000 muU/ml) was about 5 mug/adrenal/120 min. When cell suspensions were incubated with 1000 muU/ml of ACTH, the conversion from pregnenolone to corticosterone was inhibited 50% by cyanoketone at a concentration of 2 times 10(-8) M. The conversion was completely inhibited at a concentration of more than 10(-7) M. Cyanoketone up to a concentration of 10(-5) M seemed to have no inhibitory effect on cholesterol side-chain cleavage. In the absence of ACTH significant amount of pregnenolone was formed (about 60 ng/adrenal) by isolated adrenal cells obtained from normal adult female rats during incubation with 10(-7) M of cyanoketone for 60 min. To eliminate the possibility of the effect of endogenous ACTH which might be present in incubation medium, cell suspensions were obtained from hypophysectomized female rats. Incubations were carried out in the same condition as mentioned above and significant amount of pregnenolone was formed by cell suspension, which was about 35 ng/adrenal.", "contents": "[Steroidogenesis in isolated adrenal cells of rat. -Effects of cyanoketone on pregnenolone and corticosterone production- (author's transl)]. In order to study the effect of cyanoketone on steroidogenesis of rat adrenal, the assay technique for corticosteroids released into the incubated media of the rat adrenal cells treated with collagenase was basically investigated. Corticosterone was measured by fluorometric method and pregnenolone by radioimmunoassay. Reliability of radioimmunoassay was satisfactory. About 400,000 cells were obtained from one adrenal gland of male or female rats and sex-dependent difference in pregnenolone and corticosterone production in response to ACTH was not found. Net corticosterone production by isolated adrenal cells was related to the log of the concentration of ACTH by a sigmoid curve over the range 1 to 1000 muU/ml. The half-maximum response was observed at an ACTH concentration of 10 muU/ml, and maximum corticosterone production responding to ACTH (100-1000 muU/ml) was about 5 mug/adrenal/120 min. When cell suspensions were incubated with 1000 muU/ml of ACTH, the conversion from pregnenolone to corticosterone was inhibited 50% by cyanoketone at a concentration of 2 times 10(-8) M. The conversion was completely inhibited at a concentration of more than 10(-7) M. Cyanoketone up to a concentration of 10(-5) M seemed to have no inhibitory effect on cholesterol side-chain cleavage. In the absence of ACTH significant amount of pregnenolone was formed (about 60 ng/adrenal) by isolated adrenal cells obtained from normal adult female rats during incubation with 10(-7) M of cyanoketone for 60 min. To eliminate the possibility of the effect of endogenous ACTH which might be present in incubation medium, cell suspensions were obtained from hypophysectomized female rats. Incubations were carried out in the same condition as mentioned above and significant amount of pregnenolone was formed by cell suspension, which was about 35 ng/adrenal."} {"id": "PMID:170150", "title": "Androgen-dependent accumulation of carnitine by rat epididymis after injection of [3H]butyrobetaine in vivo.", "content": "After i.m. injection of [3H]butyrobetaine into rats, the accumulation of carnitine into the epididymis, prostate gland, seminal vesicles, testis and heart was studied. The concentration of radiolabeled carnitine into the cauda epididymis increased linearly with time up to 72 h after the injection of the precursor, while its level in the prostate and seminal vesicles decreased rapidly. Very low levels of carnitine were found in the testis. Castration reduced the carnitine accumulation by cauda epididymis to 6% of the control levels while treatment of castrated animals with testosterone propionate (500 mug/day) partly restored the carnitine uptake. Similar treatment with 17beta-oestradiol valerate or 17alpha-hydroxyprogesterone had no effect. Surprisingly, cyproterone acetate (5 mg/day) also significantly stimulated carnitine accumulation by the epididymis to a level above that of the castrated controls. Simultaneous injection of both cyproterone acetate and testosterone propionate to castrated animals caused an additive effect of these steroids. This indicated that cyproterone acetate in this system is working as a weak androgen. Treatment of rats with 17beta-oestradiol valerate also reduced carnitine accumulation by the cauda epididymis. This is due to suppression of pituiatry gonadotrophin secretion, since concommitant treatment with testosterone propionate (500 mug/day) caused a normalization of the carnitine uptake. Treatment of intact rats with cyproterone acetate significantly reduced the epididymal weight, but not the carnitine accumulation. 17alpha-Hydroxyprogesterone treatment had no effect either on the epididymal weight or the accumulation of the carnitine. Unilateral orchiectomy reduced the carnitine accumulation by the cauda epididymis to about 40% of that occurring in the non-operated control side. This indicates that the luminal contact between the testis and epididymis or the luminal content of the epididymis itself is of importance for the androgen-dependent metabolic process occurring in the cauda epididymis. Castration or hormone treatment did not change the conversion of butyrobetaine to carnitine, or the carnitine uptake by heart. Carnitine uptake by the testis after [3H]butyrobetaine injection was rather low and this would exclude the possibility of synthesis of carnitine in the testis as a source of epididymal carnitine. Carnitine only accumulated in the cauda epididymis in vivo 4 to 96 h after injection of [3H]butyrobetaine. The presence of radioactively labeled butyrobetaine or methylcholine was not detected.", "contents": "Androgen-dependent accumulation of carnitine by rat epididymis after injection of [3H]butyrobetaine in vivo. After i.m. injection of [3H]butyrobetaine into rats, the accumulation of carnitine into the epididymis, prostate gland, seminal vesicles, testis and heart was studied. The concentration of radiolabeled carnitine into the cauda epididymis increased linearly with time up to 72 h after the injection of the precursor, while its level in the prostate and seminal vesicles decreased rapidly. Very low levels of carnitine were found in the testis. Castration reduced the carnitine accumulation by cauda epididymis to 6% of the control levels while treatment of castrated animals with testosterone propionate (500 mug/day) partly restored the carnitine uptake. Similar treatment with 17beta-oestradiol valerate or 17alpha-hydroxyprogesterone had no effect. Surprisingly, cyproterone acetate (5 mg/day) also significantly stimulated carnitine accumulation by the epididymis to a level above that of the castrated controls. Simultaneous injection of both cyproterone acetate and testosterone propionate to castrated animals caused an additive effect of these steroids. This indicated that cyproterone acetate in this system is working as a weak androgen. Treatment of rats with 17beta-oestradiol valerate also reduced carnitine accumulation by the cauda epididymis. This is due to suppression of pituiatry gonadotrophin secretion, since concommitant treatment with testosterone propionate (500 mug/day) caused a normalization of the carnitine uptake. Treatment of intact rats with cyproterone acetate significantly reduced the epididymal weight, but not the carnitine accumulation. 17alpha-Hydroxyprogesterone treatment had no effect either on the epididymal weight or the accumulation of the carnitine. Unilateral orchiectomy reduced the carnitine accumulation by the cauda epididymis to about 40% of that occurring in the non-operated control side. This indicates that the luminal contact between the testis and epididymis or the luminal content of the epididymis itself is of importance for the androgen-dependent metabolic process occurring in the cauda epididymis. Castration or hormone treatment did not change the conversion of butyrobetaine to carnitine, or the carnitine uptake by heart. Carnitine uptake by the testis after [3H]butyrobetaine injection was rather low and this would exclude the possibility of synthesis of carnitine in the testis as a source of epididymal carnitine. Carnitine only accumulated in the cauda epididymis in vivo 4 to 96 h after injection of [3H]butyrobetaine. The presence of radioactively labeled butyrobetaine or methylcholine was not detected."} {"id": "PMID:170151", "title": "Some properties of androgen-binding activity in rat testis.", "content": "High-affinity (Ka approximately equal to 5 X 10(8) M-1 for testosterone) androgen-binding activity in rat testis was shown to have a rapid dissociation rate constant (t1/2 = 3 min, 0 degrees C, 30% glycerol buffer) using dextran-coated charcoal to separate bound from free hormone. Because of this fact, exchange of endogenous and labeled hormone was complete in the assay incubation time (16 h, 0 degrees C) and Scatchard plots of the high-affinity binding data were shown to measure total as contrasted to available sites. The binding was highly specific for androgens. Polyacrylamide gel electrophoresis separated high-affinity androgen-binding protein (Rf 0.54) from albumin (Rf 0.62). Binding site estimates under saturating conditions or by Scatchard analysis of electrophoresis data utilizing [3H]dihydrotestosterone agreed reasonably well with estimates made by the charcoal technique using [3H]testosterone.", "contents": "Some properties of androgen-binding activity in rat testis. High-affinity (Ka approximately equal to 5 X 10(8) M-1 for testosterone) androgen-binding activity in rat testis was shown to have a rapid dissociation rate constant (t1/2 = 3 min, 0 degrees C, 30% glycerol buffer) using dextran-coated charcoal to separate bound from free hormone. Because of this fact, exchange of endogenous and labeled hormone was complete in the assay incubation time (16 h, 0 degrees C) and Scatchard plots of the high-affinity binding data were shown to measure total as contrasted to available sites. The binding was highly specific for androgens. Polyacrylamide gel electrophoresis separated high-affinity androgen-binding protein (Rf 0.54) from albumin (Rf 0.62). Binding site estimates under saturating conditions or by Scatchard analysis of electrophoresis data utilizing [3H]dihydrotestosterone agreed reasonably well with estimates made by the charcoal technique using [3H]testosterone."} {"id": "PMID:170152", "title": "Similarities between 5alpha-dihydrotestosterone-receptor complexes from human and rat prostatic tissue: effects on RNA polymerase activity.", "content": "Protein macromolecules specifically binding [3H]5alpha-dihydrotestosterone ([3H]DHT) have been identified in cytosol and in nuclei prepared from human benign hypertrophic prostate. These macromolecules have similar properties to receptor proteins from other androgen-dependent tissues, as regards sedimentation coefficients on sucrose gradients and steroid specificity. Cytosol preparations from androgen-dependent tissues were able to transfer [3H]DHT in a recoverable protein-bound form to nuclei of other androgen-dependent tissues but not to nuclei of androgen-independent tissues. No transfer of radioactive steroid from cytosol of these latter tissues to any nuclei could be achieved. Labelled cytosol preparations from androgen-dependent tissues could stimulate the RNA polymerase activity of nuclei from androgen-dependent tissues but not that of nuclei from androgen-independent tissues. Cytosol preparations from these latter tissues could not affect RNA polymerase activity. Under suitable ionic conditions, human cytosol preparations containing DHT could stimulate both alpha-amanitin-sensitive and -insensitive RNA polymerase activities of human prostatic nuclei. However, rat ventral prostatic DHT-cytosol protein complexes were equally as efficient in performing this function, suggesting the possible involvement of specific DHT-receptor complexes in this process. It is therfore suggested that receptor molecules from androgen-dependent tissues may not be species specific but may share properties which would facilitate research into the understanding and aetiology of pathological conditions.", "contents": "Similarities between 5alpha-dihydrotestosterone-receptor complexes from human and rat prostatic tissue: effects on RNA polymerase activity. Protein macromolecules specifically binding [3H]5alpha-dihydrotestosterone ([3H]DHT) have been identified in cytosol and in nuclei prepared from human benign hypertrophic prostate. These macromolecules have similar properties to receptor proteins from other androgen-dependent tissues, as regards sedimentation coefficients on sucrose gradients and steroid specificity. Cytosol preparations from androgen-dependent tissues were able to transfer [3H]DHT in a recoverable protein-bound form to nuclei of other androgen-dependent tissues but not to nuclei of androgen-independent tissues. No transfer of radioactive steroid from cytosol of these latter tissues to any nuclei could be achieved. Labelled cytosol preparations from androgen-dependent tissues could stimulate the RNA polymerase activity of nuclei from androgen-dependent tissues but not that of nuclei from androgen-independent tissues. Cytosol preparations from these latter tissues could not affect RNA polymerase activity. Under suitable ionic conditions, human cytosol preparations containing DHT could stimulate both alpha-amanitin-sensitive and -insensitive RNA polymerase activities of human prostatic nuclei. However, rat ventral prostatic DHT-cytosol protein complexes were equally as efficient in performing this function, suggesting the possible involvement of specific DHT-receptor complexes in this process. It is therfore suggested that receptor molecules from androgen-dependent tissues may not be species specific but may share properties which would facilitate research into the understanding and aetiology of pathological conditions."} {"id": "PMID:170154", "title": "Apparent accelerated aging of human collagen in diabetes mellitus.", "content": "The chronologic ages of human subjects were determined experimentally by enzymatic digestion of tendon collagen samples. Determined age closely matched actual age for individuals dying with a variety of major diseases. Juvenile diabetics did not fit this pattern; their experimentally determined ages were significantly greater than their actual ages. This raises the possibility of relationships between diabetes mellitus, changes in connective tissue, and accelerated aging.", "contents": "Apparent accelerated aging of human collagen in diabetes mellitus. The chronologic ages of human subjects were determined experimentally by enzymatic digestion of tendon collagen samples. Determined age closely matched actual age for individuals dying with a variety of major diseases. Juvenile diabetics did not fit this pattern; their experimentally determined ages were significantly greater than their actual ages. This raises the possibility of relationships between diabetes mellitus, changes in connective tissue, and accelerated aging."} {"id": "PMID:170153", "title": "Androgen-binding proteins in rat epididymis: properties of a cytoplasmic receptor for androgen similar to the androgen receptor in ventral prostate and different from androgen-binding protein (ABP).", "content": "The cytoplasmic recptor (CR) in rat epididymal 105,000 g supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration of hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant for 0 degrees C for 6 h, heating at 50 degrees C for 30 min, or exposure to the sulfhydryl blocking reagent, p-chloromercuriphenylsulfonate (1mM) at 25 degrees C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5alpha-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 degrees C is greater than 2 days), while dissociation from ABP was rapid (half-time at 0 degrees C is similar to 6 min). Cyproterone acetate (250 mg/100 g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP.", "contents": "Androgen-binding proteins in rat epididymis: properties of a cytoplasmic receptor for androgen similar to the androgen receptor in ventral prostate and different from androgen-binding protein (ABP). The cytoplasmic recptor (CR) in rat epididymal 105,000 g supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration of hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant for 0 degrees C for 6 h, heating at 50 degrees C for 30 min, or exposure to the sulfhydryl blocking reagent, p-chloromercuriphenylsulfonate (1mM) at 25 degrees C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5alpha-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 degrees C is greater than 2 days), while dissociation from ABP was rapid (half-time at 0 degrees C is similar to 6 min). Cyproterone acetate (250 mg/100 g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP."} {"id": "PMID:170155", "title": "Deterioration of the microcirculation in diabetes.", "content": "Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane. Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation. The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective. The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined. The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production. The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes. The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression. A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available.", "contents": "Deterioration of the microcirculation in diabetes. Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane. Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation. The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective. The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined. The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production. The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes. The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression. A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available."} {"id": "PMID:170157", "title": "Effect of dioctyl sodium sulfosuccinate on colonic fluid and electrolyte movement.", "content": "These studies evaluated the effect of dioctyl sodium sulfosuccinate (DSS), a detergent and the active ingredient of some commercially available stool softeners, on intestinal fluid and electrolyte movement. DSS produced water, sodium and chloride secretion into the in vivo rat cecum. This secretion readily reverted to net absorption following replacement of DSS by isotonic saline. In in vitro studies, DSS increased the short circuit current and diminished sodium absorption. The increase in short circuit current was not observed either when HCO3 and chloride were absent from the incubation solution or when theophylline was present. DSS also significantly increased mucosal cyclic adenosine monophosphate levels. These results which are similar to previous studies of the effect of cholera enterotoxin on ileal mucosa and bile salts on colonic mucosa are consistent with the proposal that DSS stimulates fluid and electrolyte secretion which is mediated by increased mucosal cyclic adenosine 3':5' monophosphate.", "contents": "Effect of dioctyl sodium sulfosuccinate on colonic fluid and electrolyte movement. These studies evaluated the effect of dioctyl sodium sulfosuccinate (DSS), a detergent and the active ingredient of some commercially available stool softeners, on intestinal fluid and electrolyte movement. DSS produced water, sodium and chloride secretion into the in vivo rat cecum. This secretion readily reverted to net absorption following replacement of DSS by isotonic saline. In in vitro studies, DSS increased the short circuit current and diminished sodium absorption. The increase in short circuit current was not observed either when HCO3 and chloride were absent from the incubation solution or when theophylline was present. DSS also significantly increased mucosal cyclic adenosine monophosphate levels. These results which are similar to previous studies of the effect of cholera enterotoxin on ileal mucosa and bile salts on colonic mucosa are consistent with the proposal that DSS stimulates fluid and electrolyte secretion which is mediated by increased mucosal cyclic adenosine 3':5' monophosphate."} {"id": "PMID:170158", "title": "Control of deoxyribonucleic acid synthesis in normal rabbit colonic mucosa.", "content": "Although cyclic adenosine 3':5'-monophosphate (cyclic AMP, cAMP) is known to suppress DNA synthesis is cultured cells and experimental tumors, its role in normal intact tissue has been little explored. This study helps to define the influence of modifiers of cyclic AMP levels on DNA synthesis in rabbit colonic mucosa maintained in short term organ culture system. Base line studies showed that incorporation of [3H]thymidine into DNA was linear for 24 hr and predominantly in mucosal cells, as shown by autoradiography. Colon from a normal fed rabbit showed a gradient of DNA synthesis, lowest in the cecum and increasing to a maximum, 3-fold greater, at the splenic flexure. This pattern was obliterated by fasting, at which time no formed stool remained in the colon, and all colon mucosa incorporated thymidine at the lower level of the right colon. Known modifiers of intracellular cAMP were found to depress colonic DNA synthesis. Theophylline inhibited DNA synthesis by 35% at 0.5 mM concentration and increased intracellular cAMP levels. This inhibition took 10 hr to be manifest and was at least partly reversible. It was by far the most active of the methylxanthines, consistent with its potency as a phosphodiesterase inhibitor. N6,02-dibutyryl cyclic AMP inhibited DNA synthesis at concentrations as low as 0.025 mM, whereas adenosine and sodium butyrate were ineffective up to 1.0 mM. 5'-AMP did inhibit DNA synthesis, but only at 0.1 mM or higher and did not elevate intracellular cAMP levels. Other modifiers of cAMP which were effective included prostaglandins E1, E2, and F2alpha (2 times 10(-6) M) and papaverine (1 muM). Thymidine uptake was not affected by any of these drugs. The intrinsic thymidine pool was estimated at 20 muM by isotope dilution, and was not altered by theophylline. DNA synthesis in rabbit colon can be suppressed by increased cAMP levels within the time period allowed by organ culture. Thus, these drugs that elevated cAMP levels did not seem to suppress DNA synthesis by decreasing intracellular thymidine concentrations.", "contents": "Control of deoxyribonucleic acid synthesis in normal rabbit colonic mucosa. Although cyclic adenosine 3':5'-monophosphate (cyclic AMP, cAMP) is known to suppress DNA synthesis is cultured cells and experimental tumors, its role in normal intact tissue has been little explored. This study helps to define the influence of modifiers of cyclic AMP levels on DNA synthesis in rabbit colonic mucosa maintained in short term organ culture system. Base line studies showed that incorporation of [3H]thymidine into DNA was linear for 24 hr and predominantly in mucosal cells, as shown by autoradiography. Colon from a normal fed rabbit showed a gradient of DNA synthesis, lowest in the cecum and increasing to a maximum, 3-fold greater, at the splenic flexure. This pattern was obliterated by fasting, at which time no formed stool remained in the colon, and all colon mucosa incorporated thymidine at the lower level of the right colon. Known modifiers of intracellular cAMP were found to depress colonic DNA synthesis. Theophylline inhibited DNA synthesis by 35% at 0.5 mM concentration and increased intracellular cAMP levels. This inhibition took 10 hr to be manifest and was at least partly reversible. It was by far the most active of the methylxanthines, consistent with its potency as a phosphodiesterase inhibitor. N6,02-dibutyryl cyclic AMP inhibited DNA synthesis at concentrations as low as 0.025 mM, whereas adenosine and sodium butyrate were ineffective up to 1.0 mM. 5'-AMP did inhibit DNA synthesis, but only at 0.1 mM or higher and did not elevate intracellular cAMP levels. Other modifiers of cAMP which were effective included prostaglandins E1, E2, and F2alpha (2 times 10(-6) M) and papaverine (1 muM). Thymidine uptake was not affected by any of these drugs. The intrinsic thymidine pool was estimated at 20 muM by isotope dilution, and was not altered by theophylline. DNA synthesis in rabbit colon can be suppressed by increased cAMP levels within the time period allowed by organ culture. Thus, these drugs that elevated cAMP levels did not seem to suppress DNA synthesis by decreasing intracellular thymidine concentrations."} {"id": "PMID:170159", "title": "[The present status of the theory of induction of carcinoma of the cervix in man by herpes virus (author's transl)].", "content": "A large body of evidence has accumulated during the past decade suggesting that HSV-2 infection of the cervix may be a major precursor of cervical carcinoma. A brief review of the more significant findings to date is presented.", "contents": "[The present status of the theory of induction of carcinoma of the cervix in man by herpes virus (author's transl)]. A large body of evidence has accumulated during the past decade suggesting that HSV-2 infection of the cervix may be a major precursor of cervical carcinoma. A brief review of the more significant findings to date is presented."} {"id": "PMID:170160", "title": "[\"Chronic mastitis\" and carcinoma of the breast seen from the viewpoint of Soviet-russian pathologist (author's transl)].", "content": "The group around Prof. D. I. Golowin (Leningrad) distinguishes between the solid epithelial hyperplasia belonging to fibroadenomatosis of the breast and the solid form of lobular carcinoma in situ. The morphological details permitting the differential diagnosis are stressed (see table).", "contents": "[\"Chronic mastitis\" and carcinoma of the breast seen from the viewpoint of Soviet-russian pathologist (author's transl)]. The group around Prof. D. I. Golowin (Leningrad) distinguishes between the solid epithelial hyperplasia belonging to fibroadenomatosis of the breast and the solid form of lobular carcinoma in situ. The morphological details permitting the differential diagnosis are stressed (see table)."} {"id": "PMID:170161", "title": "[Phasecontrast cytology for intraoperative diagnosis of malignant breast lesions (author's transl)].", "content": "The efficacy of a cytodiagnostic method using a wet preparation of freshly exstirpated suspected tumorous breast tissue and phasecontrast microscopy has been evaluated in 430 cases. 95% of the carcinomas present were found with this method. The rate of wrongly positive cytological findings was less than 1%. It is discussed what advantages of this method can be achieved by a well trained cytologist for the patient and the surgical organisation. Further this new method is a means to check the frozen section findings.", "contents": "[Phasecontrast cytology for intraoperative diagnosis of malignant breast lesions (author's transl)]. The efficacy of a cytodiagnostic method using a wet preparation of freshly exstirpated suspected tumorous breast tissue and phasecontrast microscopy has been evaluated in 430 cases. 95% of the carcinomas present were found with this method. The rate of wrongly positive cytological findings was less than 1%. It is discussed what advantages of this method can be achieved by a well trained cytologist for the patient and the surgical organisation. Further this new method is a means to check the frozen section findings."} {"id": "PMID:170170", "title": "Contractility of the fallopian tube.", "content": "Recordings of intratubal pressure in women reveal a complex pattern of tubal contractions. Overall activity of the fallopian tube is increased during ovulation. During the luteal phase of the menstrual cycle, activity is depressed but never suppressed. The fallopian tube remains active during gestation in contrast with the uterus which is quiescent. The early puerperal tube displays a pattern of activity similar to that recorded during the late luteal phase of the menstrual cycle. Activation occurs during suckling and in response to exogenous oxytocin, prostaglandins, nor-adrenergic compounds, and ergot derivatives. It is concluded that contractility of the fallopian tube is less influenced by ovarian steroids than that of the uterus.", "contents": "Contractility of the fallopian tube. Recordings of intratubal pressure in women reveal a complex pattern of tubal contractions. Overall activity of the fallopian tube is increased during ovulation. During the luteal phase of the menstrual cycle, activity is depressed but never suppressed. The fallopian tube remains active during gestation in contrast with the uterus which is quiescent. The early puerperal tube displays a pattern of activity similar to that recorded during the late luteal phase of the menstrual cycle. Activation occurs during suckling and in response to exogenous oxytocin, prostaglandins, nor-adrenergic compounds, and ergot derivatives. It is concluded that contractility of the fallopian tube is less influenced by ovarian steroids than that of the uterus."} {"id": "PMID:170172", "title": "The behaviour of NAD+ and NADH in Acinetobacter calcoaceticus during n-alkane assimilation.", "content": "The behaviour of the nicotinamide adenine dinucleotides NAD+ and NADH in Acinetobacter calcoaceticus during n-alkane assimilation was studied, acetate and succinate being used as reference carbon sources. The intracellular concentration of the two nucleotides was found to increase during the exponential growth phase, reaching its maximum in the phase of decreasing growth rates. In the exponential phase, the NAD+/NADH quotients were less than 1 and showed only unimportant variations. In the phase of decreasing growth rates, the concentration of NADH showed a distinct decrease, reaching its minimum in the stationary phase. Parallel to this, the concentration of NAD+ showed a continuous increase until the stationary phase was reached. This resulted in an increase, during the phase of decreasing growth rates, of the NAD+/NADH quotients to values greater than 1, similarly as recorded in the stationary phase. There were no fundamental differences in this behaviour between the individual carbon sources.", "contents": "The behaviour of NAD+ and NADH in Acinetobacter calcoaceticus during n-alkane assimilation. The behaviour of the nicotinamide adenine dinucleotides NAD+ and NADH in Acinetobacter calcoaceticus during n-alkane assimilation was studied, acetate and succinate being used as reference carbon sources. The intracellular concentration of the two nucleotides was found to increase during the exponential growth phase, reaching its maximum in the phase of decreasing growth rates. In the exponential phase, the NAD+/NADH quotients were less than 1 and showed only unimportant variations. In the phase of decreasing growth rates, the concentration of NADH showed a distinct decrease, reaching its minimum in the stationary phase. Parallel to this, the concentration of NAD+ showed a continuous increase until the stationary phase was reached. This resulted in an increase, during the phase of decreasing growth rates, of the NAD+/NADH quotients to values greater than 1, similarly as recorded in the stationary phase. There were no fundamental differences in this behaviour between the individual carbon sources."} {"id": "PMID:170173", "title": "Penicillinamidohydrolase in Escherichia coli. III. Catabolite repression, diauxie, effect of cAMP and nature of the enzyme induction.", "content": "Synthesis of penicillinamidohydrolase (penicillin acylase, EC 3.5.1.11) in Escherichia coli is subjected to the absolute catabolite repression by glucose and partial repression by acetate. Both types of catabolite repression of synthesis of the enzyme in Escherichia coli are substantially influenced by cyclic 3',5'-adenosinemonophosphate (cAMP). Growth diauxie in a mixed medium containing glucose and phenylacetic acid serving as carbon and energy sources is overcome by cAMP. cAMP does not influence the basal rate of the enzyme synthesis (without the inducer). Derepression of synthesis of penicillinamidohydrolase by cAMP in a medium with glucose and inducer (phenylacetic acid) is associated with utilization of the inducer, due probably to derepression of other enzymes responsible for degradation of phenylacetic acid. Lactate can serve as a \"catabolically neutral\" source of carbon suitable for the maximum production of penicillinamidohydrolase. The gratuitous induction of the enzyme synthesis in a medium with lactate as the carbon and energy source and with phenylacetic acid is not influenced by cAMP; however, cAMP overcomes completely the absolute catabolite repression of the enzyme synthesis by glucose.", "contents": "Penicillinamidohydrolase in Escherichia coli. III. Catabolite repression, diauxie, effect of cAMP and nature of the enzyme induction. Synthesis of penicillinamidohydrolase (penicillin acylase, EC 3.5.1.11) in Escherichia coli is subjected to the absolute catabolite repression by glucose and partial repression by acetate. Both types of catabolite repression of synthesis of the enzyme in Escherichia coli are substantially influenced by cyclic 3',5'-adenosinemonophosphate (cAMP). Growth diauxie in a mixed medium containing glucose and phenylacetic acid serving as carbon and energy sources is overcome by cAMP. cAMP does not influence the basal rate of the enzyme synthesis (without the inducer). Derepression of synthesis of penicillinamidohydrolase by cAMP in a medium with glucose and inducer (phenylacetic acid) is associated with utilization of the inducer, due probably to derepression of other enzymes responsible for degradation of phenylacetic acid. Lactate can serve as a \"catabolically neutral\" source of carbon suitable for the maximum production of penicillinamidohydrolase. The gratuitous induction of the enzyme synthesis in a medium with lactate as the carbon and energy source and with phenylacetic acid is not influenced by cAMP; however, cAMP overcomes completely the absolute catabolite repression of the enzyme synthesis by glucose."} {"id": "PMID:170174", "title": "Cross-resistance of Escherichia coli B/r to cis-platinum (II) diamminochloride, UV light and alkylating agents.", "content": "Gradual transfers of the strain Escherichia coli B/r on M9 agar with increasing concentrations of cis-platinum (II) diamminochloride (cis-Pt(II)) yielded a resistant strain SM 405 capable of growing on liquid M9 medium containing 250 muM cis-Pt(II). The parent strain Escherichia coli B/r is completely inhibited in both division and growth at cis-Pt(II) concentrations as low as 30 muM. The resistant mutant has a longer doubling time than the parent strain. No other differences were found between the two strains. To elucidate the nature of the resistance, the effect of cis-Pt(II) on the survival of the two strains was compared with that of nitrogen mustard, UV light and ethyl methanesulphonate (EMS). The resistant strain SM 405 was found to be more hardened against the lethal action of UV light and nitrogen mustard but less so against EMS. It had also a higher ability of a host-cell reactivation of UV-irradiated phage T3. The different resistance of the B/r and SM 405 strains is probably due to a mutation increasing the effectiveness of the excision repair in the latter.", "contents": "Cross-resistance of Escherichia coli B/r to cis-platinum (II) diamminochloride, UV light and alkylating agents. Gradual transfers of the strain Escherichia coli B/r on M9 agar with increasing concentrations of cis-platinum (II) diamminochloride (cis-Pt(II)) yielded a resistant strain SM 405 capable of growing on liquid M9 medium containing 250 muM cis-Pt(II). The parent strain Escherichia coli B/r is completely inhibited in both division and growth at cis-Pt(II) concentrations as low as 30 muM. The resistant mutant has a longer doubling time than the parent strain. No other differences were found between the two strains. To elucidate the nature of the resistance, the effect of cis-Pt(II) on the survival of the two strains was compared with that of nitrogen mustard, UV light and ethyl methanesulphonate (EMS). The resistant strain SM 405 was found to be more hardened against the lethal action of UV light and nitrogen mustard but less so against EMS. It had also a higher ability of a host-cell reactivation of UV-irradiated phage T3. The different resistance of the B/r and SM 405 strains is probably due to a mutation increasing the effectiveness of the excision repair in the latter."} {"id": "PMID:170175", "title": "Personality characteristics and sleep variables.", "content": "In a sleep study of 14 normal healthy adults an investigation was made of sleep measurements of a baseline record for its eventual relationship to the percentage of increase of REM percentage of the 1st recovery night following partial differential REM deprivation (PDRD), as well as to personality characteristics. The percentage of change in NREM sleep of the 1st recovery night was compared with the baseline record andthen compared with corresponding values of REM sleep. The results are summarized as follows. No significant correlation exists between the percentage of increase in the REM percentage of the 1st recovery night and sleep measures of the baseline record. An investigation of the relationship between sleep measures of the baseline record and personality characteristics revealed that stage SWS(%) was significantly greater in the introvert than in the extrovert, in the neurotic than in the non-neurotic, and in the nervous than in the optimistic. Comparison of the changes in NREM and REM sleep percentages of the 1st recovery night with the baseline record was made between paired personality characteristics. A significantly high percentage of increase in REM percentage was almost always associated with a significantly high percentage of decrease in stage 2 percentage. From these results it was inferred that an increase in REM percentage occurs at the expense of stage 2 percentage.", "contents": "Personality characteristics and sleep variables. In a sleep study of 14 normal healthy adults an investigation was made of sleep measurements of a baseline record for its eventual relationship to the percentage of increase of REM percentage of the 1st recovery night following partial differential REM deprivation (PDRD), as well as to personality characteristics. The percentage of change in NREM sleep of the 1st recovery night was compared with the baseline record andthen compared with corresponding values of REM sleep. The results are summarized as follows. No significant correlation exists between the percentage of increase in the REM percentage of the 1st recovery night and sleep measures of the baseline record. An investigation of the relationship between sleep measures of the baseline record and personality characteristics revealed that stage SWS(%) was significantly greater in the introvert than in the extrovert, in the neurotic than in the non-neurotic, and in the nervous than in the optimistic. Comparison of the changes in NREM and REM sleep percentages of the 1st recovery night with the baseline record was made between paired personality characteristics. A significantly high percentage of increase in REM percentage was almost always associated with a significantly high percentage of decrease in stage 2 percentage. From these results it was inferred that an increase in REM percentage occurs at the expense of stage 2 percentage."} {"id": "PMID:170176", "title": "Characteristics of poor sleep with the normal human being.", "content": "1. To investigate the differences between good sleep and poor sleep, 41 sleep records were observed with nine normal male subjects ranging in ages from 22 to 40 years. A comparison was done of the differences of sleep records between the good and poor sleep estimations for each subject. 2. Poor sleep showed significantly shorter total sleep time (P less than 0.01) and significantly shorter stage 2 (P less than 0.05) than good sleep, but there were no differences in stages 1, 3, 4, stage REM, the percentage of every sleep stage to total sleep time, REM latency, mean REM duration, REM cycle and REM density. 3. Poor sleep showed longer latency for falling sleep (P less than 0.10) and a significant increase in stage changes from stage 2 to stage 3 (P less than 0.01) than with good sleep. 4. Poor sleep showed more prolonged awakenings and significantly longer durations spent for awakenings (P less than 0.05). 5. As to awakening in the morning poor sleep showed longer times required from terminal stage 2 and stage 4 and a significantly shorter time from terminal stage REM (stages 2 and 4, P less than 0.10, REM, P less than 0.01). 6. A certain amount of stage 4 and its decreasing seemed to be delayed in poor sleep, though its initial appearance wasn't. 7. REM periods of good sleep peaked at the third or the fourth REM stage and decreased to the fifth but those of poor sleep showed a gradual increasing from the second to the fifth having almost the same durations. 8. Awakenings in the morning often occurred from stage REM or just after an REM stage in poor sleep but in good sleep, on the other hand, occurred from stage 2. 9. The thresholds of natural wakenings from stages 3, 4 and REM of good sleep during the night might be higher than those of poor sleep.", "contents": "Characteristics of poor sleep with the normal human being. 1. To investigate the differences between good sleep and poor sleep, 41 sleep records were observed with nine normal male subjects ranging in ages from 22 to 40 years. A comparison was done of the differences of sleep records between the good and poor sleep estimations for each subject. 2. Poor sleep showed significantly shorter total sleep time (P less than 0.01) and significantly shorter stage 2 (P less than 0.05) than good sleep, but there were no differences in stages 1, 3, 4, stage REM, the percentage of every sleep stage to total sleep time, REM latency, mean REM duration, REM cycle and REM density. 3. Poor sleep showed longer latency for falling sleep (P less than 0.10) and a significant increase in stage changes from stage 2 to stage 3 (P less than 0.01) than with good sleep. 4. Poor sleep showed more prolonged awakenings and significantly longer durations spent for awakenings (P less than 0.05). 5. As to awakening in the morning poor sleep showed longer times required from terminal stage 2 and stage 4 and a significantly shorter time from terminal stage REM (stages 2 and 4, P less than 0.10, REM, P less than 0.01). 6. A certain amount of stage 4 and its decreasing seemed to be delayed in poor sleep, though its initial appearance wasn't. 7. REM periods of good sleep peaked at the third or the fourth REM stage and decreased to the fifth but those of poor sleep showed a gradual increasing from the second to the fifth having almost the same durations. 8. Awakenings in the morning often occurred from stage REM or just after an REM stage in poor sleep but in good sleep, on the other hand, occurred from stage 2. 9. The thresholds of natural wakenings from stages 3, 4 and REM of good sleep during the night might be higher than those of poor sleep."} {"id": "PMID:170178", "title": "[Chronobiological aspects of cyclothymia (author's transl)].", "content": "The paradoxical effect of sleep deprivation in endogenous depression has renewed the traditional interests of psychiatrists in the rhythmic phenomena associated with the symptomatology and course of cyclothymia. During the last decade, the rapid development of clinical research on sleep, neuroendocrinology, chromobiology and chronopathology in conjunction with important developments of methodology and statistical procedures have enabled a modern reconceptualization of the relationship between cyclothymia and disturbances in biological rhythms. An intensive review of the literature on circadian, ultradian, and infradian rhythms is reported here, and their relationship to the course and individual phases of cyclothymia is explored. The results of traditional analyses of sleep stages which had originally indicated that particular disturbances of sleep may be specific to cyclothymia have been shown to be incorrect. Rather, the abbreviation and fragmentation of sleep and the decrease of del asleep with concomitant increase in shallow stages have been found as well in serious sleep disturbances of other origins. Striking inter-and intra-individual variabilities in REM-sleep parameters characterize not only psychotic depression and severe mania but also a wide range of other acute psychoses...", "contents": "[Chronobiological aspects of cyclothymia (author's transl)]. The paradoxical effect of sleep deprivation in endogenous depression has renewed the traditional interests of psychiatrists in the rhythmic phenomena associated with the symptomatology and course of cyclothymia. During the last decade, the rapid development of clinical research on sleep, neuroendocrinology, chromobiology and chronopathology in conjunction with important developments of methodology and statistical procedures have enabled a modern reconceptualization of the relationship between cyclothymia and disturbances in biological rhythms. An intensive review of the literature on circadian, ultradian, and infradian rhythms is reported here, and their relationship to the course and individual phases of cyclothymia is explored. The results of traditional analyses of sleep stages which had originally indicated that particular disturbances of sleep may be specific to cyclothymia have been shown to be incorrect. Rather, the abbreviation and fragmentation of sleep and the decrease of del asleep with concomitant increase in shallow stages have been found as well in serious sleep disturbances of other origins. Striking inter-and intra-individual variabilities in REM-sleep parameters characterize not only psychotic depression and severe mania but also a wide range of other acute psychoses..."} {"id": "PMID:170179", "title": "Metabolism in normal and virus-transformed chick embryo fibroblasts as observed with glucose labeled with 14C and tritium and with tritium-labeled water.", "content": "Glucose metabolism in normal and virus-transformed chick embryo fibroblast cells in culture was observed by allowing the cells to metabolize [U-14C]glucose plus glucose labeled with tritium in the C-1, C-3, and C-6 positions. Similarities and differences between normal and transformed cells were observed and measured. Both normal and transformed cells are found to metabolize about 20% of the glucose via the oxidative pentose phosphate cycle, with the rates being about twice as much for transformed cells as for normal cells under the chosen conditions. Nevertheless, the ratio of glucose metabolized via oxidative pentose cycle to the net flow of that metabolized directly to fructose 6-phosphate is about the same in normal and transformed cells. Although the rate of flow of [14C]glucose into the tricarboxylic acid cycle intermediates and amino acids derived from them appears to be the same in normal and transformed cells, the rate of tritium incorporation from H3HO into these intermediates seems to be much higher in normal cells.", "contents": "Metabolism in normal and virus-transformed chick embryo fibroblasts as observed with glucose labeled with 14C and tritium and with tritium-labeled water. Glucose metabolism in normal and virus-transformed chick embryo fibroblast cells in culture was observed by allowing the cells to metabolize [U-14C]glucose plus glucose labeled with tritium in the C-1, C-3, and C-6 positions. Similarities and differences between normal and transformed cells were observed and measured. Both normal and transformed cells are found to metabolize about 20% of the glucose via the oxidative pentose phosphate cycle, with the rates being about twice as much for transformed cells as for normal cells under the chosen conditions. Nevertheless, the ratio of glucose metabolized via oxidative pentose cycle to the net flow of that metabolized directly to fructose 6-phosphate is about the same in normal and transformed cells. Although the rate of flow of [14C]glucose into the tricarboxylic acid cycle intermediates and amino acids derived from them appears to be the same in normal and transformed cells, the rate of tritium incorporation from H3HO into these intermediates seems to be much higher in normal cells."} {"id": "PMID:170180", "title": "Purification and properties of cytochrome c-556 from Agrobacterium tumefaciens B2a.", "content": "Cytochrome c-556 from Agrobacterium mefaciens B2a was isolated in a pure, homoneous state. The best purification procedure volved ammonium sulphate fractionation, delting on Sephadex G-25, column chromatographic fractionation on DEAE- and CM-cellulose, and gel filtration on Sephadex G-75 superfine. Substitution of the CM-cellulose step by isoelectric focusing was successful. The purity of the final preparation is warranted by the purity index value, the electrophoretic patterns in the absence and presence of sodium dodecylsulphate, the sedimentation profile and the N-terminal amino acid analysis (alanine). The absorption spectrum of reduced cytochrome c-556 has maxima at 318, 419, 526 and 555.5 nm. The molar extinction coefficient for the alpha-band is 20 200M-1cm-1. The isoelectric point, determined both by preparative and analytical isoelectric focusing, is 5.55 +/- 0.10. The molecular weight of cytochrome c-556 was determined by gel filtration as 12000 and by dodecylsulphate gel electrophoresis as 11 500.", "contents": "Purification and properties of cytochrome c-556 from Agrobacterium tumefaciens B2a. Cytochrome c-556 from Agrobacterium mefaciens B2a was isolated in a pure, homoneous state. The best purification procedure volved ammonium sulphate fractionation, delting on Sephadex G-25, column chromatographic fractionation on DEAE- and CM-cellulose, and gel filtration on Sephadex G-75 superfine. Substitution of the CM-cellulose step by isoelectric focusing was successful. The purity of the final preparation is warranted by the purity index value, the electrophoretic patterns in the absence and presence of sodium dodecylsulphate, the sedimentation profile and the N-terminal amino acid analysis (alanine). The absorption spectrum of reduced cytochrome c-556 has maxima at 318, 419, 526 and 555.5 nm. The molar extinction coefficient for the alpha-band is 20 200M-1cm-1. The isoelectric point, determined both by preparative and analytical isoelectric focusing, is 5.55 +/- 0.10. The molecular weight of cytochrome c-556 was determined by gel filtration as 12000 and by dodecylsulphate gel electrophoresis as 11 500."} {"id": "PMID:170181", "title": "Extraction of collagenase from the 6000 times g sediment of uterine and skin tissues of mice. A comparative study.", "content": "An enzyme capable of digesting native collagen in solution at neutral pH was extracted from the 6 000 times g sediment of the involuting uterus of the mouse and of the back skins of mice and rats. The collagenase could be dissociated at cold-room temperature from the sediment in about equal amounts when neutral Tris buffer containing 1.0M NaCl or 5M urea was used for the extraction step. The enzyme has been concentrated by ammonium sulfate precipitation and the activity was measured by using [14C]collagen in solution at pH 7.5. Collagen breakdown products were identified by disc electrophoresis. The amount of enzyme extracted was a function of temperature and salt concentration. As 5M urea extracted collagenase from the sediment in a relatively short time, this method of extraction seems to be a useful tool for serial experiments in the study of collagenase activity in collagen-rich tissues.", "contents": "Extraction of collagenase from the 6000 times g sediment of uterine and skin tissues of mice. A comparative study. An enzyme capable of digesting native collagen in solution at neutral pH was extracted from the 6 000 times g sediment of the involuting uterus of the mouse and of the back skins of mice and rats. The collagenase could be dissociated at cold-room temperature from the sediment in about equal amounts when neutral Tris buffer containing 1.0M NaCl or 5M urea was used for the extraction step. The enzyme has been concentrated by ammonium sulfate precipitation and the activity was measured by using [14C]collagen in solution at pH 7.5. Collagen breakdown products were identified by disc electrophoresis. The amount of enzyme extracted was a function of temperature and salt concentration. As 5M urea extracted collagenase from the sediment in a relatively short time, this method of extraction seems to be a useful tool for serial experiments in the study of collagenase activity in collagen-rich tissues."} {"id": "PMID:170182", "title": "Stimulation of collagen synthesis in a cell-free system by mRNA from chick embryos.", "content": "Embryonic chick RNA was translated in a cell-free system derived from wheat germ. One of the products synthesized in vitro under the direction of this RNA could be identified as collagen on the basis of collagenase digestion experiments and sodium dodecylsulfate-acrylamide gel electrophoresis. By submitting the RNA to chromatography on oligo(dT)-cellulose, a 26-30-fold enrichment of the mRNA coding for collagen was achieved.", "contents": "Stimulation of collagen synthesis in a cell-free system by mRNA from chick embryos. Embryonic chick RNA was translated in a cell-free system derived from wheat germ. One of the products synthesized in vitro under the direction of this RNA could be identified as collagen on the basis of collagenase digestion experiments and sodium dodecylsulfate-acrylamide gel electrophoresis. By submitting the RNA to chromatography on oligo(dT)-cellulose, a 26-30-fold enrichment of the mRNA coding for collagen was achieved."} {"id": "PMID:170186", "title": "Pathology of the early lesion in multiple sclerosis.", "content": "Ideas concerning the nature of multiple sclerosis continue to be strongly influenced by the unusual morphology of the disease. A review of classic histology studies, however, reveals that there is less agreement than might be supposed concerning several important histiological features of the early lesion. Electron microscopy of brain biopsies, of immersion fixed autopsy tissue and of autopsy tissue fixed by early in situ brain perfusion suggests that the mechanism of demyelination in multiple sclerosis may be an unusual one that involves a progressive reduction in the number of myelin lamellae around nerve fibers in the vicinity of cells of uncertain origin that contain filamentous and multilamellated cytoplasmic inclusions unlike the usual pleomorphic inclusions seen in myelin phagocytes. Lymphocytes are not directly involved in this process but are observed to contact the inclusion material following its delivery to the Virchow-Robin spaces. The putative neurogenic or viral antigen in multiple sclerosis may be contained in this material. The occurrence of filamentous nuclei in early lesions fixed by immersion is an unrelated phenomenon, which may be an autolytic or drug induced artifact although this has not yet been established.", "contents": "Pathology of the early lesion in multiple sclerosis. Ideas concerning the nature of multiple sclerosis continue to be strongly influenced by the unusual morphology of the disease. A review of classic histology studies, however, reveals that there is less agreement than might be supposed concerning several important histiological features of the early lesion. Electron microscopy of brain biopsies, of immersion fixed autopsy tissue and of autopsy tissue fixed by early in situ brain perfusion suggests that the mechanism of demyelination in multiple sclerosis may be an unusual one that involves a progressive reduction in the number of myelin lamellae around nerve fibers in the vicinity of cells of uncertain origin that contain filamentous and multilamellated cytoplasmic inclusions unlike the usual pleomorphic inclusions seen in myelin phagocytes. Lymphocytes are not directly involved in this process but are observed to contact the inclusion material following its delivery to the Virchow-Robin spaces. The putative neurogenic or viral antigen in multiple sclerosis may be contained in this material. The occurrence of filamentous nuclei in early lesions fixed by immersion is an unrelated phenomenon, which may be an autolytic or drug induced artifact although this has not yet been established."} {"id": "PMID:170187", "title": "The gangliosidoses.", "content": "The gangliosidoses are hereditary diseases with a recessive mode of inheritance and are caused by a genetically induced enzymatic block, which results in the accumulation of gangliosides in various tissues of the body, mainly in the brain. Although Tay-Sachs disease, the most commonly occurring of the gangliosidoses, has been known for nearly 100 years, additional variants of ganglioside \"storage\" disorders have been discovered during the past 15 years. Considerable progress in the knowledge of these disorders has been made with the advent of electron microscopy and with the elaboration of new biochemical and enzyme-chemical techniques. At the present the gangliosidoses are not amenable to therapy. Therefore the foreseeable future the pragmatic approach involves identification of the high-risk pregnancy and antenatal diagnosis.", "contents": "The gangliosidoses. The gangliosidoses are hereditary diseases with a recessive mode of inheritance and are caused by a genetically induced enzymatic block, which results in the accumulation of gangliosides in various tissues of the body, mainly in the brain. Although Tay-Sachs disease, the most commonly occurring of the gangliosidoses, has been known for nearly 100 years, additional variants of ganglioside \"storage\" disorders have been discovered during the past 15 years. Considerable progress in the knowledge of these disorders has been made with the advent of electron microscopy and with the elaboration of new biochemical and enzyme-chemical techniques. At the present the gangliosidoses are not amenable to therapy. Therefore the foreseeable future the pragmatic approach involves identification of the high-risk pregnancy and antenatal diagnosis."} {"id": "PMID:170188", "title": "Pathologic axons and synapses in human neuropsychiatric disorders.", "content": "Ultrastructural studies of cerebral biopsy specimens from patients with various forms of psychomotor retardation and dementia have disclosed pathologic changes in axons and presynaptic or postsynaptic processes. The clinical disorders with lesions in axons and presynaptic terminals are reviewed. Three basic abnormalities have been detected: proliferation of tubulovesicular structures which probably originate from the smooth endoplasmic reticulum, \"abnormal\" mitochondria, and proliferation of 80 to 100 A filaments. Understanding of the pathogenesis of human disorders associated with axonic or \"synaptic\" lesions will probably depend on progress in areas of basic biomedical research concerned with the synthesis and turnover of biological membranes and the packaging and secretion of neurotransmitters, elucidation of mechanisms of cytoplasmic streaming and axoplasmic flow, and biophysical and biochemical characteristics and functions of \"fibrous\" proteins (neurotubules, neurofilaments, pathologic fibrous proteins). In several cases of mental retardation of unknown etiology, abnormal dendritic spines of cortical neurons have been observed with the use of the Golgi method. These dendritic (postsynaptic) disorders have been attributed to defective development (\"dysgenesis\"). The knowledge provided by ultrastructural analysis of brain tissue from the human disorders of mental retardation or dementia is \"still formless, incomplete, lacking the essential threads of connection,\" and only future developments in lacking neurobiology will make possible the dissection of the primary phenomena from the secretory and probably irrelevant findings.", "contents": "Pathologic axons and synapses in human neuropsychiatric disorders. Ultrastructural studies of cerebral biopsy specimens from patients with various forms of psychomotor retardation and dementia have disclosed pathologic changes in axons and presynaptic or postsynaptic processes. The clinical disorders with lesions in axons and presynaptic terminals are reviewed. Three basic abnormalities have been detected: proliferation of tubulovesicular structures which probably originate from the smooth endoplasmic reticulum, \"abnormal\" mitochondria, and proliferation of 80 to 100 A filaments. Understanding of the pathogenesis of human disorders associated with axonic or \"synaptic\" lesions will probably depend on progress in areas of basic biomedical research concerned with the synthesis and turnover of biological membranes and the packaging and secretion of neurotransmitters, elucidation of mechanisms of cytoplasmic streaming and axoplasmic flow, and biophysical and biochemical characteristics and functions of \"fibrous\" proteins (neurotubules, neurofilaments, pathologic fibrous proteins). In several cases of mental retardation of unknown etiology, abnormal dendritic spines of cortical neurons have been observed with the use of the Golgi method. These dendritic (postsynaptic) disorders have been attributed to defective development (\"dysgenesis\"). The knowledge provided by ultrastructural analysis of brain tissue from the human disorders of mental retardation or dementia is \"still formless, incomplete, lacking the essential threads of connection,\" and only future developments in lacking neurobiology will make possible the dissection of the primary phenomena from the secretory and probably irrelevant findings."} {"id": "PMID:170190", "title": "Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipatrophic diabetes.", "content": "A female patient with the following symptoms has been observed: complete absence of subcutaneous fat on the arms and legs, well developed adipose tissue on the trunk and face, severe hyperlipidemia, eruptive xanthomas, insulin resistant diabetes mellitus with lack of ketoacidosis, hepatomegaly and elevated basal metabolic rate. The patient thus exhibited all characteristics of lipatrophic diabetes (Lawrence type of diabetes). The mother and a sister of the patient were found to have the same peculiar appearance and a slight hyperlipidemia but no diabetes mellitus. The combination of this type of partial lipodystrophy with severe hyperlipidemia, insulin resistant diabetes mellitus without ketoacidosis and elevated basal metabolic rate was further observed in 2 unrelated patients without known familial occurrence. Thus partial lipodystrophy of the extremities is another, previously undescribed, syndrome associated with the Lawrence type of diabetes mellitus. In the 1 family the syndrome of lipodystrophy and hyperlipidemia is dominantly inherited. Besides the autosomal recessively inherited syndrome of congenital generalized lipodystrophy there is a heterogenous group of dominantly inherited syndromes with various types of lipodystrophy.", "contents": "Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipatrophic diabetes. A female patient with the following symptoms has been observed: complete absence of subcutaneous fat on the arms and legs, well developed adipose tissue on the trunk and face, severe hyperlipidemia, eruptive xanthomas, insulin resistant diabetes mellitus with lack of ketoacidosis, hepatomegaly and elevated basal metabolic rate. The patient thus exhibited all characteristics of lipatrophic diabetes (Lawrence type of diabetes). The mother and a sister of the patient were found to have the same peculiar appearance and a slight hyperlipidemia but no diabetes mellitus. The combination of this type of partial lipodystrophy with severe hyperlipidemia, insulin resistant diabetes mellitus without ketoacidosis and elevated basal metabolic rate was further observed in 2 unrelated patients without known familial occurrence. Thus partial lipodystrophy of the extremities is another, previously undescribed, syndrome associated with the Lawrence type of diabetes mellitus. In the 1 family the syndrome of lipodystrophy and hyperlipidemia is dominantly inherited. Besides the autosomal recessively inherited syndrome of congenital generalized lipodystrophy there is a heterogenous group of dominantly inherited syndromes with various types of lipodystrophy."} {"id": "PMID:170191", "title": "Stability of X chromosomal inactivation in human somatic cells transformed by SV-40.", "content": "Clones of fibroblasts from a G6PD A heterozygote transformed with SV-40 did not express the G6PD silent allele in the transformed heteroploid cultures. In addition, transformed fibroblasts from a woman heterozygous for both G6PD A and HGPRT deficiency, subjected to selective pressure, did not reveal a single cell expressing either silent allele. Since the incidence of sex chromatin was significantly lower in these cells after transformation, it is likely that the loss of sex chromatin reflects the loss of the inactive X-chromosome at an early stage following transformation.", "contents": "Stability of X chromosomal inactivation in human somatic cells transformed by SV-40. Clones of fibroblasts from a G6PD A heterozygote transformed with SV-40 did not express the G6PD silent allele in the transformed heteroploid cultures. In addition, transformed fibroblasts from a woman heterozygous for both G6PD A and HGPRT deficiency, subjected to selective pressure, did not reveal a single cell expressing either silent allele. Since the incidence of sex chromatin was significantly lower in these cells after transformation, it is likely that the loss of sex chromatin reflects the loss of the inactive X-chromosome at an early stage following transformation."} {"id": "PMID:170192", "title": "Red cell uridine monophosphate kinase polymorphism in Japanese.", "content": "Samples from 635 unrelated Japanese blood doners in Tokyo were examined for their red cell uridine monophosphate kinase phenotypes using starch gel electrophoresis. Three phenotypes were found: UMPK1 (570, 89.76%), UMPK 2--1 (63, 9.92%) and UMPK 2 (2, 0.32%). The corresponding gene frequency for UMPK1 was 0.9472 and for UMPK2 was 0.0528. The UMPK2 frequency in the present study was slightly higher than the previously reported value for Caucasians in the United States, but the difference is not statistically significant. A study of 15 twin pairs and their parents was in agreement with the hypothesis of autosomal codominant inheritance for UMPK.", "contents": "Red cell uridine monophosphate kinase polymorphism in Japanese. Samples from 635 unrelated Japanese blood doners in Tokyo were examined for their red cell uridine monophosphate kinase phenotypes using starch gel electrophoresis. Three phenotypes were found: UMPK1 (570, 89.76%), UMPK 2--1 (63, 9.92%) and UMPK 2 (2, 0.32%). The corresponding gene frequency for UMPK1 was 0.9472 and for UMPK2 was 0.0528. The UMPK2 frequency in the present study was slightly higher than the previously reported value for Caucasians in the United States, but the difference is not statistically significant. A study of 15 twin pairs and their parents was in agreement with the hypothesis of autosomal codominant inheritance for UMPK."} {"id": "PMID:170193", "title": "Chromosome no. 1 of man and chimpanzee: identity of gene mapping for three loci: PPH, PGM1, and Pep-C.", "content": "Cytogenetic and biochemical analysis of 10 independant Chimpanzee-Mouse cell hybrids and of 18 subclones of one of these showed that PPH, PGM1 and Pep-C are localized on the Chimpanzee chromosome homologous to the human chromosome No. 1.", "contents": "Chromosome no. 1 of man and chimpanzee: identity of gene mapping for three loci: PPH, PGM1, and Pep-C. Cytogenetic and biochemical analysis of 10 independant Chimpanzee-Mouse cell hybrids and of 18 subclones of one of these showed that PPH, PGM1 and Pep-C are localized on the Chimpanzee chromosome homologous to the human chromosome No. 1."} {"id": "PMID:170195", "title": "Use of epithelial cell cultures for studies on the mechanism of transformation by chemical carcinogens.", "content": "Evidence is reviewed for and against four major theories of chemical carcinogenesis. The development of several normal and transformed epithelial cell lines which should be useful for the analysis of this problem is described. The detection of RNA viral particles in cells transformed with chemical carcinogens is a recurrent finding in studies from our own and other laboratories, but the significance of these particles in terms of the mechanism of chemical carcinogenesis remains to be determined. Finally, we have described the first mutants of chemically transformed epithelial cells which are temperature sensitive in the maintenance of the transformed phenotype. These mutants should be particularly useful for detecting the critical biochemical changes that distinguish a chemically induced tumor cell from its normal counterpart.", "contents": "Use of epithelial cell cultures for studies on the mechanism of transformation by chemical carcinogens. Evidence is reviewed for and against four major theories of chemical carcinogenesis. The development of several normal and transformed epithelial cell lines which should be useful for the analysis of this problem is described. The detection of RNA viral particles in cells transformed with chemical carcinogens is a recurrent finding in studies from our own and other laboratories, but the significance of these particles in terms of the mechanism of chemical carcinogenesis remains to be determined. Finally, we have described the first mutants of chemically transformed epithelial cells which are temperature sensitive in the maintenance of the transformed phenotype. These mutants should be particularly useful for detecting the critical biochemical changes that distinguish a chemically induced tumor cell from its normal counterpart."} {"id": "PMID:170196", "title": "Properties of cells transformed by DNA tumor viruses.", "content": "Transformation by the papovaviruses, SV40 and polyoma, is reviewed briefly, including factors that affect the frequency of transformation. Virus markers useful in the determination of the etiology of virus-free tumors are described, including viral DNA, viral mRNA, virus-induced antigens, and the rescue of infectious virus. Finally, the evidence that viral genes are involved in the maintenance of transformation is presented.", "contents": "Properties of cells transformed by DNA tumor viruses. Transformation by the papovaviruses, SV40 and polyoma, is reviewed briefly, including factors that affect the frequency of transformation. Virus markers useful in the determination of the etiology of virus-free tumors are described, including viral DNA, viral mRNA, virus-induced antigens, and the rescue of infectious virus. Finally, the evidence that viral genes are involved in the maintenance of transformation is presented."} {"id": "PMID:170200", "title": "Immunization against experimental Chagas' disease by using culture forms of Trypanosoma cruzi killed with a solution of sodium perchlorate.", "content": "Protection against infection with virulent blood (trypomastigote) forms of Trypanosoma cruzi was accomplished in mice by immunization with culture (mainly epimastigote) forms killed by treatment with sodium perchlorate. Sodium chloride, used instead of sodium perchlorate, with all other conditions kept the same, failed to kill all the organisms, indicating that the effects of the perchlorate anion were not simply ionic or osmotic, suggesting that they might be chaotropic. A single dose of the immunogen, without adjuvants, was sufficient to significantly protect against the infection. Protection was achieved by either intraperitoneal, intramuscular, or subcutaneous immunization, though the first two routes appeared to be more effective. After challenge, parasitemias were negative in 25, 29, and 17% of the animals immunized intraperitoneally, intramuscularly, and subcutaneously, respectively.", "contents": "Immunization against experimental Chagas' disease by using culture forms of Trypanosoma cruzi killed with a solution of sodium perchlorate. Protection against infection with virulent blood (trypomastigote) forms of Trypanosoma cruzi was accomplished in mice by immunization with culture (mainly epimastigote) forms killed by treatment with sodium perchlorate. Sodium chloride, used instead of sodium perchlorate, with all other conditions kept the same, failed to kill all the organisms, indicating that the effects of the perchlorate anion were not simply ionic or osmotic, suggesting that they might be chaotropic. A single dose of the immunogen, without adjuvants, was sufficient to significantly protect against the infection. Protection was achieved by either intraperitoneal, intramuscular, or subcutaneous immunization, though the first two routes appeared to be more effective. After challenge, parasitemias were negative in 25, 29, and 17% of the animals immunized intraperitoneally, intramuscularly, and subcutaneously, respectively."} {"id": "PMID:170201", "title": "Pathogenesis of simian foamy virus infection in natural and experimental hosts.", "content": "Inoculation of simian foamy virus type 1 into New Zealand white rabits resulted in an infection which was very similar to that observed in naturally infected nonhuman primates. Both intraperitoneal and intranasal inculations were found to be efficient procedures for the establishment of the infection in rabbits. Infection by the nasal route was found to be the best method, whereas no infection could be established by feeding virus in the drinking water. Once infection was established, virus persisted in the tissues and organs for as long as 264 days after inoculation, during which time the animals maintained significant levels of neutralizing antibody. Infectious virus was recovered from spleen, liver, lung, salivary gland, kidney, and, to a lesser extent, the brain. Virus was isolated from the blood only during early infection and never from the urine. A comparison of the distribution of foamy virus in naturally infected monkeys and baboon with experimentally infected rabbits showed that both groups harbored infectious virus in the same internal tissues and organs. Recovery of infectious virus from both groups of animals was accomplished by cultivation and/or co-cultivation of infected cells onto Vero cells.", "contents": "Pathogenesis of simian foamy virus infection in natural and experimental hosts. Inoculation of simian foamy virus type 1 into New Zealand white rabits resulted in an infection which was very similar to that observed in naturally infected nonhuman primates. Both intraperitoneal and intranasal inculations were found to be efficient procedures for the establishment of the infection in rabbits. Infection by the nasal route was found to be the best method, whereas no infection could be established by feeding virus in the drinking water. Once infection was established, virus persisted in the tissues and organs for as long as 264 days after inoculation, during which time the animals maintained significant levels of neutralizing antibody. Infectious virus was recovered from spleen, liver, lung, salivary gland, kidney, and, to a lesser extent, the brain. Virus was isolated from the blood only during early infection and never from the urine. A comparison of the distribution of foamy virus in naturally infected monkeys and baboon with experimentally infected rabbits showed that both groups harbored infectious virus in the same internal tissues and organs. Recovery of infectious virus from both groups of animals was accomplished by cultivation and/or co-cultivation of infected cells onto Vero cells."} {"id": "PMID:170198", "title": "Host effect on vesicular stomatitis virus morphogenesis and \"T\" particle formation in reptilian, avian, and mammalian cell lines.", "content": "The morphogenesis of vesicular stomatitis virus (VSV) in three reptilian cell lines (turtle heart, gecko lung, and viper spleen) was studied by thin section electron microscopy. Simultaneous growth studies were conducted in reptilian, chick embryo fibroblast, and BHK/21 cells to compare the yields of infectious VSV during serial passages. The mean length of gecko lung cell VSV measured from electron micrographs is statistically significantly shorter than that of VSV replicating in other reptilian systems studied. This observation, along with comparative growth studies, suggests the predilection of gecko lung cells to form \"auto-interfering\" truncated \"T\" rather than infectious \"B\" VS virions.", "contents": "Host effect on vesicular stomatitis virus morphogenesis and \"T\" particle formation in reptilian, avian, and mammalian cell lines. The morphogenesis of vesicular stomatitis virus (VSV) in three reptilian cell lines (turtle heart, gecko lung, and viper spleen) was studied by thin section electron microscopy. Simultaneous growth studies were conducted in reptilian, chick embryo fibroblast, and BHK/21 cells to compare the yields of infectious VSV during serial passages. The mean length of gecko lung cell VSV measured from electron micrographs is statistically significantly shorter than that of VSV replicating in other reptilian systems studied. This observation, along with comparative growth studies, suggests the predilection of gecko lung cells to form \"auto-interfering\" truncated \"T\" rather than infectious \"B\" VS virions."} {"id": "PMID:170202", "title": "Effect to tween 80 and aquasol A on virus plaque formation.", "content": "The enhancement of vesicular stomatitis virus plaques on human embryonic lung cells in the presence of Tween 80 or Aquasol A was studied to determine the optimal conditions for the enhancement. Enhanced numbers and sizes of vesicular stomatitis virus plaques occurred when Aquasol A or Tween 80 was added to the cell culture 30 min before virus adsorption but not when added after adsorption. These substances did not have a direct effect on the virus and did not have an effect on virus adsorption or penetration. A few other viruses and cell systems were also studied to determine if enhancement would extend to other viruses and cell systems. The cell system seemed to be important since enhancement of vesicular stomatitis virus plating efficiency did not occur on chicken embryo cells. However, the virus was also important since vaccinia virus plating efficiency was not enhanced on the human embryonic lung cell. The greatest enhancement encountered was the increase in the plating efficiency of Friend leukemia virus on S+L- cells.", "contents": "Effect to tween 80 and aquasol A on virus plaque formation. The enhancement of vesicular stomatitis virus plaques on human embryonic lung cells in the presence of Tween 80 or Aquasol A was studied to determine the optimal conditions for the enhancement. Enhanced numbers and sizes of vesicular stomatitis virus plaques occurred when Aquasol A or Tween 80 was added to the cell culture 30 min before virus adsorption but not when added after adsorption. These substances did not have a direct effect on the virus and did not have an effect on virus adsorption or penetration. A few other viruses and cell systems were also studied to determine if enhancement would extend to other viruses and cell systems. The cell system seemed to be important since enhancement of vesicular stomatitis virus plating efficiency did not occur on chicken embryo cells. However, the virus was also important since vaccinia virus plating efficiency was not enhanced on the human embryonic lung cell. The greatest enhancement encountered was the increase in the plating efficiency of Friend leukemia virus on S+L- cells."} {"id": "PMID:170203", "title": "Candidate cytomegalovirus strain for human vaccination.", "content": "A strain of human cytomegalovirus called Towne was isolated in WI-38 human fibrolast cell cultures from the urine of an infected infant. It was then passaged 125 times in WI-38, including three clonings, and a pool was prepared in the same cell substrate for use as a potential live attenuated vaccine. The Towne virus has a broad antigenicity and cross-reacts with the AD-169 strain. Several markers of the Towne virus were found which differentiated it from fresh isolates. One of these was resistance of the former to trypsin. The Towne virus was tested for freedom from oncogenicity or other harmful effects in preparation for tests in humans.", "contents": "Candidate cytomegalovirus strain for human vaccination. A strain of human cytomegalovirus called Towne was isolated in WI-38 human fibrolast cell cultures from the urine of an infected infant. It was then passaged 125 times in WI-38, including three clonings, and a pool was prepared in the same cell substrate for use as a potential live attenuated vaccine. The Towne virus has a broad antigenicity and cross-reacts with the AD-169 strain. Several markers of the Towne virus were found which differentiated it from fresh isolates. One of these was resistance of the former to trypsin. The Towne virus was tested for freedom from oncogenicity or other harmful effects in preparation for tests in humans."} {"id": "PMID:170204", "title": "Response to primary infection with Herpesvirus saimiri in immunosuppressed juvenile and newborn squirrel monkeys.", "content": "Immunosuppression of juvenile squirrel monkeys with combined azathioprine, prednisolone, and antilymphocyte globulin resulted in decreased antibody responses to viral antigens after primary infection with Herpesvirus saimiri (HVS). The virus was repeatedly isolated from the oropharynx of immunosuppressed monkeys but not from untreated infected controls. Thus immune factors are important in inhibiting shedding of HVS from the oropharynx. HVS could be isolated from the peripheral blood lymphocytes of infected control monkeys but not from the lymphocytes of immunosuppressed monkeys. Immunosuppressed monkeys also had decreased percentages of lymphocytes capable of forming rosettes with sheep erythrocytes. These results indicate that the immunosuppressive agents had inhibitory effects on lymphocytes (presumably thymus derived) capable of being latently infected with HVS. Antibody responses in newborn monkeys infected with HVS were delayed compared with juvenile monkeys. Treatment of newborn monkeys with antilymphocyte globulin had no suppressive effect on antibody responses to HVS.", "contents": "Response to primary infection with Herpesvirus saimiri in immunosuppressed juvenile and newborn squirrel monkeys. Immunosuppression of juvenile squirrel monkeys with combined azathioprine, prednisolone, and antilymphocyte globulin resulted in decreased antibody responses to viral antigens after primary infection with Herpesvirus saimiri (HVS). The virus was repeatedly isolated from the oropharynx of immunosuppressed monkeys but not from untreated infected controls. Thus immune factors are important in inhibiting shedding of HVS from the oropharynx. HVS could be isolated from the peripheral blood lymphocytes of infected control monkeys but not from the lymphocytes of immunosuppressed monkeys. Immunosuppressed monkeys also had decreased percentages of lymphocytes capable of forming rosettes with sheep erythrocytes. These results indicate that the immunosuppressive agents had inhibitory effects on lymphocytes (presumably thymus derived) capable of being latently infected with HVS. Antibody responses in newborn monkeys infected with HVS were delayed compared with juvenile monkeys. Treatment of newborn monkeys with antilymphocyte globulin had no suppressive effect on antibody responses to HVS."} {"id": "PMID:170205", "title": "Affinity chromatography purification of Clostridium perfringens enterotoxin.", "content": "Anti-enterotoxin immunoglobulins immobilized on CH-Sepharose or CNBr-Sepharose were used for affinity chromatography purification of Clostridium perfringens enterotoxin. Cell extracts containing enterotoxin or partially purified toxin preparations were applied to the column and nonspecifically-bound protein was eluted. NaOH was used to elute specifically bound toxin. The purity of enterotoxin purified by Sephadex G-100 chromatography followed by affinity chromatography appears similar to toxin highly purified by conventional means. The procedure can be used successfully for the rapid (less than 2 h) purification of small amounts of enterotoxin.", "contents": "Affinity chromatography purification of Clostridium perfringens enterotoxin. Anti-enterotoxin immunoglobulins immobilized on CH-Sepharose or CNBr-Sepharose were used for affinity chromatography purification of Clostridium perfringens enterotoxin. Cell extracts containing enterotoxin or partially purified toxin preparations were applied to the column and nonspecifically-bound protein was eluted. NaOH was used to elute specifically bound toxin. The purity of enterotoxin purified by Sephadex G-100 chromatography followed by affinity chromatography appears similar to toxin highly purified by conventional means. The procedure can be used successfully for the rapid (less than 2 h) purification of small amounts of enterotoxin."} {"id": "PMID:170206", "title": "Neutralizing antibody responses to varicella-zoster virus.", "content": "Neutralization of varicella-zoster (V-Z) virus by human sera and immune rhesus monkey sera was enhanced by fresh guinea pig complement. There was no marked difference in the degree to which complement enhanced neutralization by sera from current V-Z virus infections and sera from long-past varicella infections. Immunoglobulin G neutralizing antibody in sera from varicella cases was enhanced by complement to a slightly higher degree than was immunoglobulin M (IgM) antibody, and immunoglobulin G neutralizing antibody in immune monkey sera was enhanced to a much greater degree than was IgM antibody. There was a rapid decline in the complement requirement of IgM neutralizing antibodies over the course of immunization of the rhesus monkeys. V-Z neutralizing antibody titers in the presence of complement were higher than complement-fixing titers of the same sera in all groups of individuals studied. IgM neutralizing antibody for V-Z virus was demonstrable in all cases of varicella but in only 1 of 22 zoster cases, and V-Z IgM neutralizing antibody was not detectable in primary herpes simplex virus infections in which heterotypic antibody titer rises occurred to V-Z virus. Complement-fixing antibody for V-Z virus was absent in 19S serum fractions which contained IgM neutralizing antibody for the virus.", "contents": "Neutralizing antibody responses to varicella-zoster virus. Neutralization of varicella-zoster (V-Z) virus by human sera and immune rhesus monkey sera was enhanced by fresh guinea pig complement. There was no marked difference in the degree to which complement enhanced neutralization by sera from current V-Z virus infections and sera from long-past varicella infections. Immunoglobulin G neutralizing antibody in sera from varicella cases was enhanced by complement to a slightly higher degree than was immunoglobulin M (IgM) antibody, and immunoglobulin G neutralizing antibody in immune monkey sera was enhanced to a much greater degree than was IgM antibody. There was a rapid decline in the complement requirement of IgM neutralizing antibodies over the course of immunization of the rhesus monkeys. V-Z neutralizing antibody titers in the presence of complement were higher than complement-fixing titers of the same sera in all groups of individuals studied. IgM neutralizing antibody for V-Z virus was demonstrable in all cases of varicella but in only 1 of 22 zoster cases, and V-Z IgM neutralizing antibody was not detectable in primary herpes simplex virus infections in which heterotypic antibody titer rises occurred to V-Z virus. Complement-fixing antibody for V-Z virus was absent in 19S serum fractions which contained IgM neutralizing antibody for the virus."} {"id": "PMID:170207", "title": "Increased adhesion of Chinese hamster ovary cells to substratum by cholera enterotoxin.", "content": "A new, simple assay method using Chinese hamster ovary cells was devised for cholera enterotoxin. The effect of the cholera toxin was measured by an increase in cell adhesion to the substratum. The increase was dependent on the concentration of the toxin used and was effective for a longer period of time than that of adhesion increased by dibutyryl cyclic adenosine monophosphate and theophyline. There was a delay of about 60 min before the increase in adhesion, using the toxin, appeared, whereas the increase caused by dibutyryl cyclic adenosine monophosphate appeared almost at once.", "contents": "Increased adhesion of Chinese hamster ovary cells to substratum by cholera enterotoxin. A new, simple assay method using Chinese hamster ovary cells was devised for cholera enterotoxin. The effect of the cholera toxin was measured by an increase in cell adhesion to the substratum. The increase was dependent on the concentration of the toxin used and was effective for a longer period of time than that of adhesion increased by dibutyryl cyclic adenosine monophosphate and theophyline. There was a delay of about 60 min before the increase in adhesion, using the toxin, appeared, whereas the increase caused by dibutyryl cyclic adenosine monophosphate appeared almost at once."} {"id": "PMID:170208", "title": "Characterization of monkey peripheral neutrophil granules during infection.", "content": "Rhesus monkey (Macaca mulatta) neutrophils were shown to contain the azurophilic granule maker enzymes myeloperoxidase and beta-glucuronidase but were deficient in the specific granule markers alkaline phosphatase (AKP) and lysozyme. Isopycnic centrifugation of leukocyte homogenates on linear sucrose gradients resulted in cosedimentation of myeloperoxidase and beta-glucuronidase with an equilibrium density of 1.18. After an intravenous inoculation of monkeys with Salmonella typhimurium AKP activity became marked, whereas that of beta-glucuronidase decreased and myeloperoxidase remained unchanged. Lysozyme was undetected throughout the course of the experiment, but was present in oil-induced peritoneal macrophages and peripheral mononuclear cells. The induced AKP exhibited partial latency and had an equilibrium density of 1.15. It is unclear, however, whether the induced AKP is associated with specific granules or cytoplasmic membranes. Hence, while these data are consistent with the presence of azurophilic granules in polymorphonuclear neutrophils from infected monkeys, the presence of specific granules in polymorphonuclear neutrophils of both uninfected and infected monkeys remains moot.", "contents": "Characterization of monkey peripheral neutrophil granules during infection. Rhesus monkey (Macaca mulatta) neutrophils were shown to contain the azurophilic granule maker enzymes myeloperoxidase and beta-glucuronidase but were deficient in the specific granule markers alkaline phosphatase (AKP) and lysozyme. Isopycnic centrifugation of leukocyte homogenates on linear sucrose gradients resulted in cosedimentation of myeloperoxidase and beta-glucuronidase with an equilibrium density of 1.18. After an intravenous inoculation of monkeys with Salmonella typhimurium AKP activity became marked, whereas that of beta-glucuronidase decreased and myeloperoxidase remained unchanged. Lysozyme was undetected throughout the course of the experiment, but was present in oil-induced peritoneal macrophages and peripheral mononuclear cells. The induced AKP exhibited partial latency and had an equilibrium density of 1.15. It is unclear, however, whether the induced AKP is associated with specific granules or cytoplasmic membranes. Hence, while these data are consistent with the presence of azurophilic granules in polymorphonuclear neutrophils from infected monkeys, the presence of specific granules in polymorphonuclear neutrophils of both uninfected and infected monkeys remains moot."} {"id": "PMID:170209", "title": "Ultraviolet inactivation of Epstein-Barr virus: effect on synthesis of virus-associated antigens.", "content": "The relative sensitivity to ultraviolet (UV) light of genome functions of the P3HR-1 strain of Epstein-Barr virus (EBV) was studied. The formation of viral capsid antigen (VCA) appeared to be more sensitive than that of early antigen (EA), while the synthesis of membrane antigen (MA) was most resistant, as seen on examination in the presence of cytosine arabinoside (Ara-C). However, the appearance of both VCA and EA, but not that of MA, was delayed with UV-irradiated virus, in either the presence or absence of Ara-C. The synthesis of EA and VCA induced by UV-irradiated virus was suppressed in the presence of Ara-C, while that of MA was not.", "contents": "Ultraviolet inactivation of Epstein-Barr virus: effect on synthesis of virus-associated antigens. The relative sensitivity to ultraviolet (UV) light of genome functions of the P3HR-1 strain of Epstein-Barr virus (EBV) was studied. The formation of viral capsid antigen (VCA) appeared to be more sensitive than that of early antigen (EA), while the synthesis of membrane antigen (MA) was most resistant, as seen on examination in the presence of cytosine arabinoside (Ara-C). However, the appearance of both VCA and EA, but not that of MA, was delayed with UV-irradiated virus, in either the presence or absence of Ara-C. The synthesis of EA and VCA induced by UV-irradiated virus was suppressed in the presence of Ara-C, while that of MA was not."} {"id": "PMID:170210", "title": "Production by EBV infection of an EBNA-positive subline from an EBNA-negative human lymphoma cell line without detectable EBV DNA.", "content": "A continuous lymphoma cell line, BJAB, derived from the tumour of an exceptional African case of Burkitt's lymphoma, has previously been described. Unlike 97% of African BL cases studied, neither the original tumour cells nor the cell line contained detectable amounts of EBV (Epstein-Barr virus) DNA, nor did they express the EBV-determined nuclear antigen EBNA. The cells of the established line had the characteristics of B-type lymphocytes and they carried receptors for EBV. EBNA was induced in the majority of BJAB cells after EBV infection. Usually the cells died within 10 days of infection, but it was possible to establish a permanent EBNA-positive variant (GC-BJAB) of BJAB. The patient from whose tumour the original BJAB line was established was seropositive for EBV antigens, indicating previous exposure to and continuing presence of the virus; yet the tumour had not become infected by EBV. This evidence shows that EBV is not readily \"picked up\" by the lymphoma.", "contents": "Production by EBV infection of an EBNA-positive subline from an EBNA-negative human lymphoma cell line without detectable EBV DNA. A continuous lymphoma cell line, BJAB, derived from the tumour of an exceptional African case of Burkitt's lymphoma, has previously been described. Unlike 97% of African BL cases studied, neither the original tumour cells nor the cell line contained detectable amounts of EBV (Epstein-Barr virus) DNA, nor did they express the EBV-determined nuclear antigen EBNA. The cells of the established line had the characteristics of B-type lymphocytes and they carried receptors for EBV. EBNA was induced in the majority of BJAB cells after EBV infection. Usually the cells died within 10 days of infection, but it was possible to establish a permanent EBNA-positive variant (GC-BJAB) of BJAB. The patient from whose tumour the original BJAB line was established was seropositive for EBV antigens, indicating previous exposure to and continuing presence of the virus; yet the tumour had not become infected by EBV. This evidence shows that EBV is not readily \"picked up\" by the lymphoma."} {"id": "PMID:170211", "title": "Vaccination against feline leukaemia virus using a cell membrane antigen system.", "content": "Cats inoculated with live feline lymphoblastoid cells of the FL74 line developed high titres of antibody to feline oncornavirus-associated cell membrane antigen (FOCMA). Eight cats were subsequently challenged with a large dose of feline leukaemia virus (FeLV) of a highly pathogenic strain. All resisted infection while 10 cats given the challenge virus alone became infected. The FeLV produced by FL74 cells was shown to be of extremely low infectivity in cats and in cultured feline cells. Cats inoculated with either FL74 cells or virus purified from them did not become infected. The purified virus did not induce FOCMA antibody in cats not previously exposed to FeLV. The fact that FL74 cells are highly immunogenic, but produce virus of low infectivity, is of value in devising vaccines against FeLV. Cats were also inoculated with FL74 cells which had been inactivated with paraformaldehyde. They developed FOCMA antibody, reaching a peak titre of 256, and no virus could be cultured either from the vaccine preparations or from the tissues of the cats.", "contents": "Vaccination against feline leukaemia virus using a cell membrane antigen system. Cats inoculated with live feline lymphoblastoid cells of the FL74 line developed high titres of antibody to feline oncornavirus-associated cell membrane antigen (FOCMA). Eight cats were subsequently challenged with a large dose of feline leukaemia virus (FeLV) of a highly pathogenic strain. All resisted infection while 10 cats given the challenge virus alone became infected. The FeLV produced by FL74 cells was shown to be of extremely low infectivity in cats and in cultured feline cells. Cats inoculated with either FL74 cells or virus purified from them did not become infected. The purified virus did not induce FOCMA antibody in cats not previously exposed to FeLV. The fact that FL74 cells are highly immunogenic, but produce virus of low infectivity, is of value in devising vaccines against FeLV. Cats were also inoculated with FL74 cells which had been inactivated with paraformaldehyde. They developed FOCMA antibody, reaching a peak titre of 256, and no virus could be cultured either from the vaccine preparations or from the tissues of the cats."} {"id": "PMID:170212", "title": "Histological and combined chemoimmunostimulation therapy studies against a murine leukemia.", "content": "A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 times 10(6) tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2-week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug-treated animals. A significant number of long-term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol-extracted residue of BCG) to animals in a drug-induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MER alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long-term survivors. The implication of these results for cancer therapy is discussed.", "contents": "Histological and combined chemoimmunostimulation therapy studies against a murine leukemia. A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 times 10(6) tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2-week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug-treated animals. A significant number of long-term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol-extracted residue of BCG) to animals in a drug-induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MER alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long-term survivors. The implication of these results for cancer therapy is discussed."} {"id": "PMID:170213", "title": "Immunization against Marek's disease using Marek's disease virus-specific antigens free from infectious virus.", "content": "Immunity against Marek's disease was conferred by the use of non-infectious materials extracted with non-ionic detergents from cells infected with the attenuated strain of Marek's disease virus (MDV). Antibody-free Rhode Island Red chicks were inoculated at 1 week of age with cell extracts emulsified in Freund's complete adjuvant and were given a second inoculation 1 week later without adjuvant. Protection against natural infection was obtained in groups inoculated with both soluble (not sedimented at 100,000 times g/2h) and insoluble antigens present in Nonidet P40 (NP40) extract, but only with the insoluble fraction of deoxycholate extract. The results suggest that the immunizing antigens can be partially solubilized with 0.5% NP40 and that the growth and spread of MDV are reduced in immunized chickens.", "contents": "Immunization against Marek's disease using Marek's disease virus-specific antigens free from infectious virus. Immunity against Marek's disease was conferred by the use of non-infectious materials extracted with non-ionic detergents from cells infected with the attenuated strain of Marek's disease virus (MDV). Antibody-free Rhode Island Red chicks were inoculated at 1 week of age with cell extracts emulsified in Freund's complete adjuvant and were given a second inoculation 1 week later without adjuvant. Protection against natural infection was obtained in groups inoculated with both soluble (not sedimented at 100,000 times g/2h) and insoluble antigens present in Nonidet P40 (NP40) extract, but only with the insoluble fraction of deoxycholate extract. The results suggest that the immunizing antigens can be partially solubilized with 0.5% NP40 and that the growth and spread of MDV are reduced in immunized chickens."} {"id": "PMID:170214", "title": "Spleen-cell cytotoxicity for cytomegalovirus-transformed cells. II. Inhibition by cytomegalovirus antiserum.", "content": "Serum from hamsters immunized repeatedly with cytomegalovirus (CMV) was able to block spleen-cell cytotoxicity for CMV-infected and CMV-transformed cells. Inhibition was observed regardless of whether spleen cells were obtained from hamsters sensitized to the virus or to isografts of the transformed cells (designated Cx-90-3B, T-2). Such serum did not significantly block effector cell response against transformed cells expressing herpes simplex virus or SV40-associated membrane antigens. The mechanism of blocking was investigated. It was found that the blocking activity could be adsorbed out with Cx-90-3B, T-2 cells but not by untransformed hamster embryo fibroblasts. Cx-90-3B, T-2 target cells treated with serum, and then washed, remained resistant to effector cell attack. On the other hand, if serum-treated attacker cells were washed their cytotoxic activity was not significantly impaired. These results suggest that the blocking factor in the serum is antibody-directed against cytomegalovirus-related membrane antigen. This conclusion is supported by the finding that the serum contained antibody specifically reactive with the transformed cell surface in isotopic antiglobulin tests.", "contents": "Spleen-cell cytotoxicity for cytomegalovirus-transformed cells. II. Inhibition by cytomegalovirus antiserum. Serum from hamsters immunized repeatedly with cytomegalovirus (CMV) was able to block spleen-cell cytotoxicity for CMV-infected and CMV-transformed cells. Inhibition was observed regardless of whether spleen cells were obtained from hamsters sensitized to the virus or to isografts of the transformed cells (designated Cx-90-3B, T-2). Such serum did not significantly block effector cell response against transformed cells expressing herpes simplex virus or SV40-associated membrane antigens. The mechanism of blocking was investigated. It was found that the blocking activity could be adsorbed out with Cx-90-3B, T-2 cells but not by untransformed hamster embryo fibroblasts. Cx-90-3B, T-2 target cells treated with serum, and then washed, remained resistant to effector cell attack. On the other hand, if serum-treated attacker cells were washed their cytotoxic activity was not significantly impaired. These results suggest that the blocking factor in the serum is antibody-directed against cytomegalovirus-related membrane antigen. This conclusion is supported by the finding that the serum contained antibody specifically reactive with the transformed cell surface in isotopic antiglobulin tests."} {"id": "PMID:170216", "title": "Tumour-associated transplantation antigen in sera of rats with large RSV-induced sarcomas.", "content": "A factor inhibiting tumour growth in syngeneic hosts was found in the sera of inbred Lewis rats carrying Rous sarcoma virus-induced tumour (RSL). The findings presented here suggest that the serum factor is a tumour-associated transplantation antigen (TATA) shed from the neoplasm into the circulation. All the tumour bearers' sera tested with RSL cells were negative in indirect membrane immunofluorescence;however, on passive transfer into syngeneic rats, they protected the animals against the growth of an RSL tumour inoculum. A similar protective effect was also observed after injection of TATA prepared from RSL cell membranes by solubilization with potassium cholate. When incorporated into Freund's adjuvant, tumour-bearers' sera immunized the animals against a subsequent RSL sarcoma graft. Sera collected from immunosuppressed rats bearing large sarcomas which presumably contain neither tumour-specific antibody nor antigen-antibody complexes, transferred inhibition of tumour growth to syngeneic hosts. Intact immunological reactivity of recipients was a necessary prerequisite for the protective effect of sera, since the passive transfer of an inhibitory serum to immunosuppressed rats did not inhibit tumour growth. We assume that the TATA present in tumour-bearers' serum is released from the growing neoplasm as a result of either cell death or membrane metabolic turnover.", "contents": "Tumour-associated transplantation antigen in sera of rats with large RSV-induced sarcomas. A factor inhibiting tumour growth in syngeneic hosts was found in the sera of inbred Lewis rats carrying Rous sarcoma virus-induced tumour (RSL). The findings presented here suggest that the serum factor is a tumour-associated transplantation antigen (TATA) shed from the neoplasm into the circulation. All the tumour bearers' sera tested with RSL cells were negative in indirect membrane immunofluorescence;however, on passive transfer into syngeneic rats, they protected the animals against the growth of an RSL tumour inoculum. A similar protective effect was also observed after injection of TATA prepared from RSL cell membranes by solubilization with potassium cholate. When incorporated into Freund's adjuvant, tumour-bearers' sera immunized the animals against a subsequent RSL sarcoma graft. Sera collected from immunosuppressed rats bearing large sarcomas which presumably contain neither tumour-specific antibody nor antigen-antibody complexes, transferred inhibition of tumour growth to syngeneic hosts. Intact immunological reactivity of recipients was a necessary prerequisite for the protective effect of sera, since the passive transfer of an inhibitory serum to immunosuppressed rats did not inhibit tumour growth. We assume that the TATA present in tumour-bearers' serum is released from the growing neoplasm as a result of either cell death or membrane metabolic turnover."} {"id": "PMID:170217", "title": "Appearance of C-type virus-like particles after co-cultivation of a human tumor-cell line with rat (XC) cells.", "content": "A serially progagated cell line (L104) was established by co-cultivation of alung adenocarcinoma (L-1) from a patient with concurrent chronic lymphocytic leukemia and XC, a non-producer rat line, known to carry the Rous sarcoma virus (RSV) genome. Karyotype of the L104 cultures revealed predominantly rat-like patterns; however, about 5% of the cells reacted with HLA antibodies and demonstrated human isozyme patterns. Electron microscopy of L104 cells revealed the presence of C-type particles budding from the cell membranes and in cytoplasmic vacuoles. Virus was not detected in any of the other normal lung, lung tumor or XC cells examined after co-cultivation with XC cells. The particles isolated from tissue culture fluids had the biochemical and biophysical characteristics common to other known mammalian C-type particles and were serologically related to the woolly monkey virus (WMV)/gibbon ape leukemia virus (GaLV) complex. Cross-hybridization between viral 3H-DNA transcripts and cellular RNAs from virus-infected cells clearly show the presence of sequences in the L104 cellular RNA related to both the GaLV/WMV group of viruses and rat viruses. Hydroxyapatite chromatography reveals however that the primate-related sequences in the viral RNA are indistinguishable from WMV in thermal elution profile. The host range of L104 virus appears to vary greatly from WMV in being xenotropic and, in the cell lines thus far tested appears, to infect only rat cells. The virus gave positive KC but negative XC assays. Inoculation of whole cells or cell-free supernatants into weaning hamster did not result in either solid tumors or leukemia. Co-cultivation of appropriate cell lines may represent an approach to the detection of latent viruses in human neoplasia.", "contents": "Appearance of C-type virus-like particles after co-cultivation of a human tumor-cell line with rat (XC) cells. A serially progagated cell line (L104) was established by co-cultivation of alung adenocarcinoma (L-1) from a patient with concurrent chronic lymphocytic leukemia and XC, a non-producer rat line, known to carry the Rous sarcoma virus (RSV) genome. Karyotype of the L104 cultures revealed predominantly rat-like patterns; however, about 5% of the cells reacted with HLA antibodies and demonstrated human isozyme patterns. Electron microscopy of L104 cells revealed the presence of C-type particles budding from the cell membranes and in cytoplasmic vacuoles. Virus was not detected in any of the other normal lung, lung tumor or XC cells examined after co-cultivation with XC cells. The particles isolated from tissue culture fluids had the biochemical and biophysical characteristics common to other known mammalian C-type particles and were serologically related to the woolly monkey virus (WMV)/gibbon ape leukemia virus (GaLV) complex. Cross-hybridization between viral 3H-DNA transcripts and cellular RNAs from virus-infected cells clearly show the presence of sequences in the L104 cellular RNA related to both the GaLV/WMV group of viruses and rat viruses. Hydroxyapatite chromatography reveals however that the primate-related sequences in the viral RNA are indistinguishable from WMV in thermal elution profile. The host range of L104 virus appears to vary greatly from WMV in being xenotropic and, in the cell lines thus far tested appears, to infect only rat cells. The virus gave positive KC but negative XC assays. Inoculation of whole cells or cell-free supernatants into weaning hamster did not result in either solid tumors or leukemia. Co-cultivation of appropriate cell lines may represent an approach to the detection of latent viruses in human neoplasia."} {"id": "PMID:170218", "title": "Temperature-dependent properties of cells transformed by a thermosensitive mutant (TS-121) of polyoma virus. II. Characterization of 121-6 cells.", "content": "The properties of 121-6 cells were characterized. This cell line is transformed by ts-121, a temperature-sensitive mutant of polyoma virus. Both the morphology and saturation density of the 121-6 cells were affected by temperature; i.e. at 39 degrees C, the cells grew to monolayer sheets and remained contact inhibitied for a long time (at least 25 days), while at 35 degrees C, they grew beyond the monolayer density, like cells transformed by wild-type polyoma virus. These phenotypic changes were reversible, but increased agglutinability by Concanavalin A, which was another phenotype of these transformed cells, was not temperature-sensitive, and even at high temperature, 121-6 cells, like transformed cells, showed high agglutinability.", "contents": "Temperature-dependent properties of cells transformed by a thermosensitive mutant (TS-121) of polyoma virus. II. Characterization of 121-6 cells. The properties of 121-6 cells were characterized. This cell line is transformed by ts-121, a temperature-sensitive mutant of polyoma virus. Both the morphology and saturation density of the 121-6 cells were affected by temperature; i.e. at 39 degrees C, the cells grew to monolayer sheets and remained contact inhibitied for a long time (at least 25 days), while at 35 degrees C, they grew beyond the monolayer density, like cells transformed by wild-type polyoma virus. These phenotypic changes were reversible, but increased agglutinability by Concanavalin A, which was another phenotype of these transformed cells, was not temperature-sensitive, and even at high temperature, 121-6 cells, like transformed cells, showed high agglutinability."} {"id": "PMID:170219", "title": "Genetic control of oncogenesis by murine sarcoma virus Moloney pseudotype. I. Genetics of resistance in AKR mice.", "content": "Infection of Moloney mouse sarcoma virus (M-MSV) in adult mice of several inbred strains revealed that all strains except AKR are highly susceptible to M-MSV tumor development. F1 hybrids between AKR and CBA, DBA/2 or NIH mice are as resistant (93%) as the parental AKR strain, which indicates that resistance is transmitted as a dominant character. First backcross mice to the susceptible parent show a 3:1 ratio of resistant to susceptible mice. This is the expected ratio for two segregating loci which independently confer resistance. The incidence of resistant F2 mice is somewhat lower than expected. Further support for the two-gene hypothesis was obtained in second backcross mice. None of the major genes affecting MuLV infection (Fv-2 and H-2) seems to play any role in this system and no linkage was found with Thy. 1 and albino, dilute, agouti and brown markers.", "contents": "Genetic control of oncogenesis by murine sarcoma virus Moloney pseudotype. I. Genetics of resistance in AKR mice. Infection of Moloney mouse sarcoma virus (M-MSV) in adult mice of several inbred strains revealed that all strains except AKR are highly susceptible to M-MSV tumor development. F1 hybrids between AKR and CBA, DBA/2 or NIH mice are as resistant (93%) as the parental AKR strain, which indicates that resistance is transmitted as a dominant character. First backcross mice to the susceptible parent show a 3:1 ratio of resistant to susceptible mice. This is the expected ratio for two segregating loci which independently confer resistance. The incidence of resistant F2 mice is somewhat lower than expected. Further support for the two-gene hypothesis was obtained in second backcross mice. None of the major genes affecting MuLV infection (Fv-2 and H-2) seems to play any role in this system and no linkage was found with Thy. 1 and albino, dilute, agouti and brown markers."} {"id": "PMID:170220", "title": "Genetic control of oncogenesis by murine sarcoma virus Moloney pseudotype. II. A dominant epistatic susceptibility gene.", "content": "We have shown in the preceding paper that AKR mice are highly resistant to M-MSV tumor development, and that resistance is transmitted as a dominant character. In the present studies the tumor-response pattern of F1 hybrids between resistant AKR and susceptible strains (C57Bl/6, BALB/c and B10BR) following injection with Moloney mouse sarcoma virus (M-MSV) resembles that of the non-AKR parent. Segregation is observed in first backcross (Bc1) and F2 mice, and the segregation ratios up to Bc3 mice fit a one-gene model. The data of triple cross hybrids suggests that this dominant susceptibility gene inhibits the phenotypic expression of M-MSV tumor resistance in some susceptible Fv1bb strains as well as in their hybrids with AKR. Neither Fv-1 nor H-2 exerts any significant influence on this complex system.", "contents": "Genetic control of oncogenesis by murine sarcoma virus Moloney pseudotype. II. A dominant epistatic susceptibility gene. We have shown in the preceding paper that AKR mice are highly resistant to M-MSV tumor development, and that resistance is transmitted as a dominant character. In the present studies the tumor-response pattern of F1 hybrids between resistant AKR and susceptible strains (C57Bl/6, BALB/c and B10BR) following injection with Moloney mouse sarcoma virus (M-MSV) resembles that of the non-AKR parent. Segregation is observed in first backcross (Bc1) and F2 mice, and the segregation ratios up to Bc3 mice fit a one-gene model. The data of triple cross hybrids suggests that this dominant susceptibility gene inhibits the phenotypic expression of M-MSV tumor resistance in some susceptible Fv1bb strains as well as in their hybrids with AKR. Neither Fv-1 nor H-2 exerts any significant influence on this complex system."} {"id": "PMID:170221", "title": "Immunotherapy and vaccination against cancer with non-living BCG and cord factor (trehalose-6,6'-dimycolate).", "content": "A vaccine containing non-living BCG and living tumour cells prevented the growth of 106 tumour cells introduced distally into the skin of guinea-pigs at the time of vaccination. A similar effect was achieved when living tumour cells of the vaccine were replaced by tumour cells pretreated with mitomycin C. The efficacy of the vaccine was significantly increased when cord factor was added to the vaccination mixture. The percentage of cures was about 88% (17 cases) in experiments in which the vaccine contained living tumour cells, 100% (10 cases) when mitomycin C-treated cells were used. The significance and implications of the above findings are discussed.", "contents": "Immunotherapy and vaccination against cancer with non-living BCG and cord factor (trehalose-6,6'-dimycolate). A vaccine containing non-living BCG and living tumour cells prevented the growth of 106 tumour cells introduced distally into the skin of guinea-pigs at the time of vaccination. A similar effect was achieved when living tumour cells of the vaccine were replaced by tumour cells pretreated with mitomycin C. The efficacy of the vaccine was significantly increased when cord factor was added to the vaccination mixture. The percentage of cures was about 88% (17 cases) in experiments in which the vaccine contained living tumour cells, 100% (10 cases) when mitomycin C-treated cells were used. The significance and implications of the above findings are discussed."} {"id": "PMID:170222", "title": "Detection of virus-specific DNA sequences by quantitative in situ hybridization during infection with SV40.", "content": "In situ hybridization has been used as a quantitative method to study the replication of SV40 during lytic infection. Various parameters have been defined such as fixation and denaturation of cytological preparations, concentration of complementary (3H)-cRNA and volume of buffer used for the hybridization reaction. When all these parameters are carefully controlled, a reproducibility of +/-10% can be obtained for the quantitative study of the system SV40-monkey kidney cells (CV-1). In this system, it is evident that the synthesis of viral DNA is not synchronized in confluent cells. Moreover, a proportion of 20 to 30% of cells are not labelled whatever the multiplicity of infection. In SV40-transformed cells, it was not possible to detect significantly the integrated genome due either to the small size of the genome or to the fact that the number of genome-equivalents integrated at the same place is too low to yield a radioactivitity superior to background level for long periods of exposure.", "contents": "Detection of virus-specific DNA sequences by quantitative in situ hybridization during infection with SV40. In situ hybridization has been used as a quantitative method to study the replication of SV40 during lytic infection. Various parameters have been defined such as fixation and denaturation of cytological preparations, concentration of complementary (3H)-cRNA and volume of buffer used for the hybridization reaction. When all these parameters are carefully controlled, a reproducibility of +/-10% can be obtained for the quantitative study of the system SV40-monkey kidney cells (CV-1). In this system, it is evident that the synthesis of viral DNA is not synchronized in confluent cells. Moreover, a proportion of 20 to 30% of cells are not labelled whatever the multiplicity of infection. In SV40-transformed cells, it was not possible to detect significantly the integrated genome due either to the small size of the genome or to the fact that the number of genome-equivalents integrated at the same place is too low to yield a radioactivitity superior to background level for long periods of exposure."} {"id": "PMID:170223", "title": "Transformation of mouse cells after infection with ultraviolet irradiation-inactivated herpes simplex virus type 2.", "content": "A transformed mouse cell line (H238) was obtained following the infection of 238 mouse cells with ultraviolet (UV) irradiation-inactivated herpes simplex virus type 2 (HSV-2). The transformed cells produced tumors with a 100% incidence within 8 weeks in 6-week-old syngeneic BALB/c mice at an inoculum of 1 times 10(6). Indirect immunofluorescence (IF) tests revealed the presence of HSV antigens in the transformed cells. Antibodies to HSV-2 were found in the sera of tumor-bearing animals by neutralization and IF techniques. Neither HSV-2 infectious virus nor viral antigens could be detected by the transfer of transformed-cell DNA into permissive cells.", "contents": "Transformation of mouse cells after infection with ultraviolet irradiation-inactivated herpes simplex virus type 2. A transformed mouse cell line (H238) was obtained following the infection of 238 mouse cells with ultraviolet (UV) irradiation-inactivated herpes simplex virus type 2 (HSV-2). The transformed cells produced tumors with a 100% incidence within 8 weeks in 6-week-old syngeneic BALB/c mice at an inoculum of 1 times 10(6). Indirect immunofluorescence (IF) tests revealed the presence of HSV antigens in the transformed cells. Antibodies to HSV-2 were found in the sera of tumor-bearing animals by neutralization and IF techniques. Neither HSV-2 infectious virus nor viral antigens could be detected by the transfer of transformed-cell DNA into permissive cells."} {"id": "PMID:170224", "title": "Cell-mediated cytotoxicity to chemically-induced rat tumours.", "content": "Cell-mediated immune reactions against carcinogen-induced rat tumours were demonstrated by the in vitro microcytotoxicity test. Lymph-node cells from syngeneic rats immunized against individual aminoazo-dye-induced hepatomas or 3-methylcholanthrene-induced sarcomas were cytotoxic for cells of the immunizing tumour compared with the effects of normal lymph-node cells. Only a low level of cross-reactivity was detectable against target cells derived from otherr tumours. Conversely, lymph-node cells from tumour -bearing rats were cross-reactive against a range of tumour cells, suggesting that the tumour-bearer was sensitized against a common antigen(s) as well as the individually specific antigen associated with these tumours. Lymph-node cells were reactive at an early time (from day 2) after tumour implantation and their cytotoxic potential persisted until terminal stages of tumour growth. Spleen cells from tumour-bearer and tumour-immune donors also exhibited comparable cytotoxic reactivities of the same specificity as that shown by lymph-node cell preparations. These findings are discussed in relation to the development of cell-mediated immune responses in the tumour-bearing rat and in immunized rats which are capable of rejecting transplanted tumour cells.", "contents": "Cell-mediated cytotoxicity to chemically-induced rat tumours. Cell-mediated immune reactions against carcinogen-induced rat tumours were demonstrated by the in vitro microcytotoxicity test. Lymph-node cells from syngeneic rats immunized against individual aminoazo-dye-induced hepatomas or 3-methylcholanthrene-induced sarcomas were cytotoxic for cells of the immunizing tumour compared with the effects of normal lymph-node cells. Only a low level of cross-reactivity was detectable against target cells derived from otherr tumours. Conversely, lymph-node cells from tumour -bearing rats were cross-reactive against a range of tumour cells, suggesting that the tumour-bearer was sensitized against a common antigen(s) as well as the individually specific antigen associated with these tumours. Lymph-node cells were reactive at an early time (from day 2) after tumour implantation and their cytotoxic potential persisted until terminal stages of tumour growth. Spleen cells from tumour-bearer and tumour-immune donors also exhibited comparable cytotoxic reactivities of the same specificity as that shown by lymph-node cell preparations. These findings are discussed in relation to the development of cell-mediated immune responses in the tumour-bearing rat and in immunized rats which are capable of rejecting transplanted tumour cells."} {"id": "PMID:170225", "title": "Strain-dependent expression of endogenous mouse-tropic leukemia viruses in chemically induced murine leukemias.", "content": "The effects of two chemical carcinogens, nitrosobutylurea and 7,12-dimethylbenz-(a) anthracene, on the expression of endogenous N- and B-tropic viruses were studied. The mice used were from two inbred strains, C57BL/6 and DDD-Fvr, and from 13 partially inbred strains derived from the cross of C57BL/6 with DDD-Ffr. These mouse strains are classified into three groups by the pattern of expression of endogenous viruses in normal, aged mice: (1) negative for both viruses; (2) positive for N-tropic virus only; and (3) positive for both viruses. Mice were given the carcinogens, and were tested at various intervals by the UV-XC procedure for the viruses in the spleens and other enlarged organs. Irrespective of the presence or absence of leukemias, the carcinogen-treated mice showed the same pattern of expression of endogenous viruses as that of non-treated normal mice. It can be concluded that the activation of the endogenous viruses is dependent on the mouse strains and that the growth of the activated viruses is not a necessary step for the chemical induction of leukemias.", "contents": "Strain-dependent expression of endogenous mouse-tropic leukemia viruses in chemically induced murine leukemias. The effects of two chemical carcinogens, nitrosobutylurea and 7,12-dimethylbenz-(a) anthracene, on the expression of endogenous N- and B-tropic viruses were studied. The mice used were from two inbred strains, C57BL/6 and DDD-Fvr, and from 13 partially inbred strains derived from the cross of C57BL/6 with DDD-Ffr. These mouse strains are classified into three groups by the pattern of expression of endogenous viruses in normal, aged mice: (1) negative for both viruses; (2) positive for N-tropic virus only; and (3) positive for both viruses. Mice were given the carcinogens, and were tested at various intervals by the UV-XC procedure for the viruses in the spleens and other enlarged organs. Irrespective of the presence or absence of leukemias, the carcinogen-treated mice showed the same pattern of expression of endogenous viruses as that of non-treated normal mice. It can be concluded that the activation of the endogenous viruses is dependent on the mouse strains and that the growth of the activated viruses is not a necessary step for the chemical induction of leukemias."} {"id": "PMID:170226", "title": "Isozyme pattern of fructose diphosphate aldolase during hepatocarcinogenesis induced by 2-acetylaminofluorene in rat liver.", "content": "The biosynthesis of aldolase A and B subunits has been studied in rat liver during the administration of carcinogen AAF4. Transition from a predominance of aldolase B to A was observed during carcinogenesis in rat liver. Changes in isozymic pattern and FDP to F-1-P cleavage activity ratio were observed before histological alterations typical of hepatoma could be detected. Our data support the hypothesis of dedifferentiation during hepatocarcinogenesis which in an early stage results in switching on of the gene for aldolase A with simultaneous continuation of biosynthesis of aldolase B within single cells.", "contents": "Isozyme pattern of fructose diphosphate aldolase during hepatocarcinogenesis induced by 2-acetylaminofluorene in rat liver. The biosynthesis of aldolase A and B subunits has been studied in rat liver during the administration of carcinogen AAF4. Transition from a predominance of aldolase B to A was observed during carcinogenesis in rat liver. Changes in isozymic pattern and FDP to F-1-P cleavage activity ratio were observed before histological alterations typical of hepatoma could be detected. Our data support the hypothesis of dedifferentiation during hepatocarcinogenesis which in an early stage results in switching on of the gene for aldolase A with simultaneous continuation of biosynthesis of aldolase B within single cells."} {"id": "PMID:170227", "title": "Narcotic antagonists: a reasonable method of treating narcotic dependency.", "content": "Historically, narcotic dependence has been treated primarily by substituting one narcotic drug for another. One alternative chemical treatment for narcotic dependency is through the use of a narcotic antagonist. The present study involves the observed side effects and outcome results of treating 40 male heroin addicts with the narcotic antagonist, cyclazocine, in the context of a comprehensive psychotherapeutic program. It is concluded that the side effects of cyclazocine are minimal, that cyclazocine is not diverted to the streets, and that it is an effective tool in the context of a comprehensive treatment program for narcotic-dependent individuals.", "contents": "Narcotic antagonists: a reasonable method of treating narcotic dependency. Historically, narcotic dependence has been treated primarily by substituting one narcotic drug for another. One alternative chemical treatment for narcotic dependency is through the use of a narcotic antagonist. The present study involves the observed side effects and outcome results of treating 40 male heroin addicts with the narcotic antagonist, cyclazocine, in the context of a comprehensive psychotherapeutic program. It is concluded that the side effects of cyclazocine are minimal, that cyclazocine is not diverted to the streets, and that it is an effective tool in the context of a comprehensive treatment program for narcotic-dependent individuals."} {"id": "PMID:170228", "title": "Liver disease in drug addicts: clinical course-toxicological and clinical pharmacological aspects.", "content": "Drug addicts admitted to the hospital had acute hepatitis in 44%, chronic hepatitis in 34%, toxic liver injury in 16%. About 50% of the patients with acute hepatitis were HAA positive. Patients with intravenous drug abuse acquired acute hepatitis after a mean period of 1.8 years. Acute hepatitis in drug addicts shows a prolonged course in the majority of the cases. Biochemically increases in serum bilirubin and transaminase levels are less pronounced as compared to non-addicted persons. 30-35% of the patients develop chronic hepatitis. Speed abuse promotes the tendency to cholestasis in acute episodes of liver disease. A toxic effect of the drug preparations upon the liver cells is assumed. Chronic hepatitis in drug addicts mainly develops from earlier acute hepatitis with prolonged course. In our material, the percentage of chronic hepatitis at present is 47.5%. Besides toxic effects, also repeated infections have to be discussed with regard the etiology and pathogenesis of the disease.", "contents": "Liver disease in drug addicts: clinical course-toxicological and clinical pharmacological aspects. Drug addicts admitted to the hospital had acute hepatitis in 44%, chronic hepatitis in 34%, toxic liver injury in 16%. About 50% of the patients with acute hepatitis were HAA positive. Patients with intravenous drug abuse acquired acute hepatitis after a mean period of 1.8 years. Acute hepatitis in drug addicts shows a prolonged course in the majority of the cases. Biochemically increases in serum bilirubin and transaminase levels are less pronounced as compared to non-addicted persons. 30-35% of the patients develop chronic hepatitis. Speed abuse promotes the tendency to cholestasis in acute episodes of liver disease. A toxic effect of the drug preparations upon the liver cells is assumed. Chronic hepatitis in drug addicts mainly develops from earlier acute hepatitis with prolonged course. In our material, the percentage of chronic hepatitis at present is 47.5%. Besides toxic effects, also repeated infections have to be discussed with regard the etiology and pathogenesis of the disease."} {"id": "PMID:170229", "title": "Clinical pathologic observations in pseudoxanthoma elasticum.", "content": "Skin biopsy material obtained from 2 patients with pseudoxanthoma elasticum associated with congenital hyperphosphatasia was compared with skin biopsy material obtained from 3 patients with pseudoxanthoma elasticum unassociated with any other disease. Clinically normal skin showed calcification of normal-appearing elastin as the initial change in pseudoxanthoma elasticum. Elastin fibers become more ravelled as the disease progresses. A previously unreported early transient calcification of collagen was demonstrated. Other abnormal collagen forms may also be present. The Von Kossa stain appears to be the stain of choice for identifying these earliest histologic changes.", "contents": "Clinical pathologic observations in pseudoxanthoma elasticum. Skin biopsy material obtained from 2 patients with pseudoxanthoma elasticum associated with congenital hyperphosphatasia was compared with skin biopsy material obtained from 3 patients with pseudoxanthoma elasticum unassociated with any other disease. Clinically normal skin showed calcification of normal-appearing elastin as the initial change in pseudoxanthoma elasticum. Elastin fibers become more ravelled as the disease progresses. A previously unreported early transient calcification of collagen was demonstrated. Other abnormal collagen forms may also be present. The Von Kossa stain appears to be the stain of choice for identifying these earliest histologic changes."} {"id": "PMID:170230", "title": "Sialography with continuous measurement of pressure outside and inside the gland.", "content": "In almost any method of sialography the results depend on a sign given by the patient. In order to eliminate this very uncertain factor or to limit its effect, a procedure was established to determine the pressure in the gland after the injection of contrast medium, as well as the injection pressure during injection. The difference between injection pressure and gland pressure was minimized through the use of special cannulas. A special syringe was used. Pressure was recorded by a membrane transducer connected to electronic equipment. It appears that the pressures are below or about the same as the diastolic blood pressure. Pressure values do not correlate with the volumes injected. The standard deviation of the pressure is too large to make entirely superfluous the sign given by the patient; nevertheless, the method improves the quality and reliability of sialogram readings and extends the field of application to patients unable to give reliable subjective information.", "contents": "Sialography with continuous measurement of pressure outside and inside the gland. In almost any method of sialography the results depend on a sign given by the patient. In order to eliminate this very uncertain factor or to limit its effect, a procedure was established to determine the pressure in the gland after the injection of contrast medium, as well as the injection pressure during injection. The difference between injection pressure and gland pressure was minimized through the use of special cannulas. A special syringe was used. Pressure was recorded by a membrane transducer connected to electronic equipment. It appears that the pressures are below or about the same as the diastolic blood pressure. Pressure values do not correlate with the volumes injected. The standard deviation of the pressure is too large to make entirely superfluous the sign given by the patient; nevertheless, the method improves the quality and reliability of sialogram readings and extends the field of application to patients unable to give reliable subjective information."} {"id": "PMID:170234", "title": "[The Rothmund-Thomson-syndrome. A case report].", "content": "This case of Rothmund-Thomson Syndrome is presented because of its association with hitherto unrecognized disorders, especially internal malignancy. The position and linkage of these associated symptomes with the genetically determined syndrome of Rothmund and Thomson is discussed.", "contents": "[The Rothmund-Thomson-syndrome. A case report]. This case of Rothmund-Thomson Syndrome is presented because of its association with hitherto unrecognized disorders, especially internal malignancy. The position and linkage of these associated symptomes with the genetically determined syndrome of Rothmund and Thomson is discussed."} {"id": "PMID:170239", "title": "Wildlife and environmental health: raccoons as indicators of zoonoses and pollutants in southeastern United States.", "content": "Inasmuch as terrestrial fauna are an integral part of our natural environment and are directly exposed to disease and pollutants, it follows that certain wild populations could serve to detect subtle alterations within ecosystems. A collection of studies on raccoons is presented to stimulate other researchers to develop the potential of our wildlife resources as monitors of environmental health. Raccoons have been used as serologic sentinels for St Louis encephalitis and Venezuelan equine encephalomyelitis. Studies suggest that the raccoon may be used as an indicator of leptospirosis, tularemia, and some enteric bacteria and viruses. Base line surveys have defined (1) residue levels of organochlorine and organophosphate compounds and (2) body burdens of mercury, cesium-137, and strontium-90. Physiologic responses, parasite burdens, and reproductive processes are also considered as measures that may reflect pertinent information about environmental health.", "contents": "Wildlife and environmental health: raccoons as indicators of zoonoses and pollutants in southeastern United States. Inasmuch as terrestrial fauna are an integral part of our natural environment and are directly exposed to disease and pollutants, it follows that certain wild populations could serve to detect subtle alterations within ecosystems. A collection of studies on raccoons is presented to stimulate other researchers to develop the potential of our wildlife resources as monitors of environmental health. Raccoons have been used as serologic sentinels for St Louis encephalitis and Venezuelan equine encephalomyelitis. Studies suggest that the raccoon may be used as an indicator of leptospirosis, tularemia, and some enteric bacteria and viruses. Base line surveys have defined (1) residue levels of organochlorine and organophosphate compounds and (2) body burdens of mercury, cesium-137, and strontium-90. Physiologic responses, parasite burdens, and reproductive processes are also considered as measures that may reflect pertinent information about environmental health."} {"id": "PMID:170240", "title": "EM49, a new peptide antibiotic IV. The structure of EM49.", "content": "EM49 is a family of similar peptide antibiotics, each an octapeptide acylated with a beta-hydroxy fatty acid. This paper described the determination of the structure of the fatty acyl residue, the selective removal of this residue from the peptide portion of the molecule, and the sequential analysis of the peptide by the EDMAN method. The structure of EM49, 1, is derived by this degradation.", "contents": "EM49, a new peptide antibiotic IV. The structure of EM49. EM49 is a family of similar peptide antibiotics, each an octapeptide acylated with a beta-hydroxy fatty acid. This paper described the determination of the structure of the fatty acyl residue, the selective removal of this residue from the peptide portion of the molecule, and the sequential analysis of the peptide by the EDMAN method. The structure of EM49, 1, is derived by this degradation."} {"id": "PMID:170235", "title": "A teaching evaluation questionnaire for postmyocardial infarction patients.", "content": "The above report is primarily a methodologic presentation of a questionnaire designed to assess the knowledge of patients with a recent myocardial infarction (MI) concerning the nature of their disease, emergency treatment, diet and smoking, resumption of physical activity, psychological factors important in heart disease, and problems encountered when returning home and to work. This questionnaire was designed to asses an in-hospital teaching program for post-MI patients in these areas. Test, re-test results from our first group of 24 patients indicated they significantly increased their knowledge about problems surrounding their return home and to work during their time in the hospital. The failure of these patients to demonstrate a learning effect in the other areas covered has stimulated changes in the teaching program.", "contents": "A teaching evaluation questionnaire for postmyocardial infarction patients. The above report is primarily a methodologic presentation of a questionnaire designed to assess the knowledge of patients with a recent myocardial infarction (MI) concerning the nature of their disease, emergency treatment, diet and smoking, resumption of physical activity, psychological factors important in heart disease, and problems encountered when returning home and to work. This questionnaire was designed to asses an in-hospital teaching program for post-MI patients in these areas. Test, re-test results from our first group of 24 patients indicated they significantly increased their knowledge about problems surrounding their return home and to work during their time in the hospital. The failure of these patients to demonstrate a learning effect in the other areas covered has stimulated changes in the teaching program."} {"id": "PMID:170241", "title": "Sleep patterns afted graded exercise.", "content": "The effects of six graded and measured exercise activities on sleep patterns were investigated in two healthy young men. Electrophysiological recording were made continuously throughout the night to distinguish sleep states. This experiment was designed to test the hypothesis of a relation between physical activity and slow-wave sleep (SWS: stages 3 and 4 of non-REM sleep). A progressive increase in SWS over the whole-night sleep record was found with progressively increasing physical fatigue. A fall in rapid-eye-movement (REM) sleep and at higher exercise levels, of stage 2 sleep, was found. The results support the hypothesis that SWS is involved in the recovery process from fatigue.", "contents": "Sleep patterns afted graded exercise. The effects of six graded and measured exercise activities on sleep patterns were investigated in two healthy young men. Electrophysiological recording were made continuously throughout the night to distinguish sleep states. This experiment was designed to test the hypothesis of a relation between physical activity and slow-wave sleep (SWS: stages 3 and 4 of non-REM sleep). A progressive increase in SWS over the whole-night sleep record was found with progressively increasing physical fatigue. A fall in rapid-eye-movement (REM) sleep and at higher exercise levels, of stage 2 sleep, was found. The results support the hypothesis that SWS is involved in the recovery process from fatigue."} {"id": "PMID:170242", "title": "A new gas lesion syndrome in man, induced by \"isobaric gas counterdiffusion\".", "content": "Normal men have been found to develop pruritus and gas bubble lesions in the skin, and disruption of vestibular function, when breathing nitrogen or neon with oxygen while surrounded by helium at increased ambient pressure. This phenomenon, which occurs at stable ambient pressures, at 1 or many ATA, has been designated the \"isobaric gas counterdiffusion syndrome.\" In a series of analyses and experiments in vivo and in vitro the cause of the syndrome has been established as due to gas accumulation and development of gas bubbles in tissues as a result of differences in selective diffusivities, for various respired and ambient gases, in the tissue substances between capillary blood and the surrounding atmosphere. The phenomenon here described in man is an initial stage of a process shown later in animals to progress to continuous, massive, lethal, intravascular gas embolization.", "contents": "A new gas lesion syndrome in man, induced by \"isobaric gas counterdiffusion\". Normal men have been found to develop pruritus and gas bubble lesions in the skin, and disruption of vestibular function, when breathing nitrogen or neon with oxygen while surrounded by helium at increased ambient pressure. This phenomenon, which occurs at stable ambient pressures, at 1 or many ATA, has been designated the \"isobaric gas counterdiffusion syndrome.\" In a series of analyses and experiments in vivo and in vitro the cause of the syndrome has been established as due to gas accumulation and development of gas bubbles in tissues as a result of differences in selective diffusivities, for various respired and ambient gases, in the tissue substances between capillary blood and the surrounding atmosphere. The phenomenon here described in man is an initial stage of a process shown later in animals to progress to continuous, massive, lethal, intravascular gas embolization."} {"id": "PMID:170243", "title": "Respiratory capacity, cyclic adenosine 3',5'-monophosphate, and morphogenesis of Mucor racemosus.", "content": "A variety of cultural conditions were examined to determine the relationship between respiratory capacity and the growth of Mucor racemosus in the yeast and mycelial form. The results show that both yeasts and hyphae can develop when the respiratory capacity is low (e.g., in N2). In addition, the yeast form of the fungus could be grown in air in the presence of cyclic adenosine 5'-monophosphate with high respiratory rates characteristic of air-grown mycelia. These results indicate that their is not an obligatory relationship between respiratory capacity and morphogenesis in M. racemosus. Low intracellular levels of cyclic adenosine 5'-monophosphate, however, were correlated with aerobic mycelial development, whereas yeast development under CO2 was characterized by higher cyclic adenosine 5'-monophosphate levels.", "contents": "Respiratory capacity, cyclic adenosine 3',5'-monophosphate, and morphogenesis of Mucor racemosus. A variety of cultural conditions were examined to determine the relationship between respiratory capacity and the growth of Mucor racemosus in the yeast and mycelial form. The results show that both yeasts and hyphae can develop when the respiratory capacity is low (e.g., in N2). In addition, the yeast form of the fungus could be grown in air in the presence of cyclic adenosine 5'-monophosphate with high respiratory rates characteristic of air-grown mycelia. These results indicate that their is not an obligatory relationship between respiratory capacity and morphogenesis in M. racemosus. Low intracellular levels of cyclic adenosine 5'-monophosphate, however, were correlated with aerobic mycelial development, whereas yeast development under CO2 was characterized by higher cyclic adenosine 5'-monophosphate levels."} {"id": "PMID:170244", "title": "Operator-promoter functions in the threonine operon of Escherichia coli.", "content": "The prophage curing properties of secondary-site lysogens of coliphage lambda have been studied. The site of integration in the original lysogen (L79) is within the ooerator-promoter region of the thr operon. As a result, expression of the thr enzymes is reduced, and the strain is a leaky threonine auxotroph. Heat pulse curing of strain L79 and a thr+ lysogenic revertant (L79-20) showed that heat pulse curing of both lysogens was int and xis dependent and occurred by correct excisions of the prophage. The heat pulse curing restored strain L79 to prototrophy whereas strain L79-20 synthesized the thr enzymes constitutively and at high levels. This indicates that the reversion mutation in strain L79-20 occurred outside of the prophage and within the operator-promoter region of the thr operon. In contrast, spontaneous curing of both lysogens occurred by both correct and incorrect excisions. Spontaneously cured derivatives of strain L79-20 gave rise to three classes of regulatory mutants affecting operator and promoter functions to the thr operon.", "contents": "Operator-promoter functions in the threonine operon of Escherichia coli. The prophage curing properties of secondary-site lysogens of coliphage lambda have been studied. The site of integration in the original lysogen (L79) is within the ooerator-promoter region of the thr operon. As a result, expression of the thr enzymes is reduced, and the strain is a leaky threonine auxotroph. Heat pulse curing of strain L79 and a thr+ lysogenic revertant (L79-20) showed that heat pulse curing of both lysogens was int and xis dependent and occurred by correct excisions of the prophage. The heat pulse curing restored strain L79 to prototrophy whereas strain L79-20 synthesized the thr enzymes constitutively and at high levels. This indicates that the reversion mutation in strain L79-20 occurred outside of the prophage and within the operator-promoter region of the thr operon. In contrast, spontaneous curing of both lysogens occurred by both correct and incorrect excisions. Spontaneously cured derivatives of strain L79-20 gave rise to three classes of regulatory mutants affecting operator and promoter functions to the thr operon."} {"id": "PMID:170245", "title": "Neurospora crassa conidial germination: role of endogenous amino acid pools.", "content": "The levels of the endogenous amino acid pools in conidia, germinating conidia, and mycelia of wild-type Neurospora crassa were measured. Three different chromatographic procedures employing the amino acid analyzer were used to identify and quantitatively measure 28 different ninhydrin-positive compounds. All of the common amino acids were detected in conidial extracts except proline, methionine, and cystine. The levels of these three amino acid pools were also very low in mycelia. During the first hour of germination in minimal medium, the levels of most of the free amino acid pools decreased. The pool of glutamic acid, the predominant free amino acid in conidia, decreased 70% during the first hour. Very little glutamic acid or any other amino acid was excreted into the medium. During the first 20 min of germination, the decrease in the glutamic acid pool was nearly equivalent to the increase in the aspartic acid pool. The aspartic acid and lambda-aminobutyric acid pools were the only amino acid pools that increased to maximum levels within the first 20 min of germination and then decreased. It is proposed that an important metabolic event that occurs during the early stages of conidial germination is the production of reduced pyridine nucleotides. The degradation of the large glutamic acid pool existing in the conidia (2.5% of the conidial dry weight) could produce these reduced coenzymes.", "contents": "Neurospora crassa conidial germination: role of endogenous amino acid pools. The levels of the endogenous amino acid pools in conidia, germinating conidia, and mycelia of wild-type Neurospora crassa were measured. Three different chromatographic procedures employing the amino acid analyzer were used to identify and quantitatively measure 28 different ninhydrin-positive compounds. All of the common amino acids were detected in conidial extracts except proline, methionine, and cystine. The levels of these three amino acid pools were also very low in mycelia. During the first hour of germination in minimal medium, the levels of most of the free amino acid pools decreased. The pool of glutamic acid, the predominant free amino acid in conidia, decreased 70% during the first hour. Very little glutamic acid or any other amino acid was excreted into the medium. During the first 20 min of germination, the decrease in the glutamic acid pool was nearly equivalent to the increase in the aspartic acid pool. The aspartic acid and lambda-aminobutyric acid pools were the only amino acid pools that increased to maximum levels within the first 20 min of germination and then decreased. It is proposed that an important metabolic event that occurs during the early stages of conidial germination is the production of reduced pyridine nucleotides. The degradation of the large glutamic acid pool existing in the conidia (2.5% of the conidial dry weight) could produce these reduced coenzymes."} {"id": "PMID:170246", "title": "Genetic analysis of succinate utilization in enzyme I mutants of the phosphoenolpyruvate: sugar phosphotransferase system in Escherichia coli.", "content": "Studies on the reversion characteristics of Escherichia coli strains carrying various mutations in the pts region have led to the recognition of a mutation, suc-1, with a previously undescribed phenotype. Strains carrying the suc-1 mutation grow normally on most sources of carbon but are unable to utilize succinate effectively. The suc-1 mutation can be separated genetically from the tightly linked ptsI6 mutation. Reversion of suc-1 mutants for growth on succinate yields interesting classes of suppressor mutations.", "contents": "Genetic analysis of succinate utilization in enzyme I mutants of the phosphoenolpyruvate: sugar phosphotransferase system in Escherichia coli. Studies on the reversion characteristics of Escherichia coli strains carrying various mutations in the pts region have led to the recognition of a mutation, suc-1, with a previously undescribed phenotype. Strains carrying the suc-1 mutation grow normally on most sources of carbon but are unable to utilize succinate effectively. The suc-1 mutation can be separated genetically from the tightly linked ptsI6 mutation. Reversion of suc-1 mutants for growth on succinate yields interesting classes of suppressor mutations."} {"id": "PMID:170247", "title": "Independent constitutive expression of the aerobic and anaerobic pathways of glycerol catabolism in Klebsiella aerogenes.", "content": "Klebsiella aerogenes dissimilates glycerol aerobically via an inducible pathway initiated by an adenosine triphosphate-linked kinase that converts the substrate to sn-glycerol 3-phosphate. Phosphorylated glycerol is then dehydrogenated to dihydroxyacetone phosphate by an enzyme characteristic of a flavoprotein. Anaerobically, the organism dissimilates glycerol via an inducible pathway initiated by a nicotinamide adenine dinucleotide-linked dehydrogenase that converts the substrate to dihydroxyacetone. The keto product is then phosphorylated by another adenosine triphosphate-linked kinase. Two kinds of constitutive mutants have been isolated: one affecting the aerobic and the other the anaerobic pathway.", "contents": "Independent constitutive expression of the aerobic and anaerobic pathways of glycerol catabolism in Klebsiella aerogenes. Klebsiella aerogenes dissimilates glycerol aerobically via an inducible pathway initiated by an adenosine triphosphate-linked kinase that converts the substrate to sn-glycerol 3-phosphate. Phosphorylated glycerol is then dehydrogenated to dihydroxyacetone phosphate by an enzyme characteristic of a flavoprotein. Anaerobically, the organism dissimilates glycerol via an inducible pathway initiated by a nicotinamide adenine dinucleotide-linked dehydrogenase that converts the substrate to dihydroxyacetone. The keto product is then phosphorylated by another adenosine triphosphate-linked kinase. Two kinds of constitutive mutants have been isolated: one affecting the aerobic and the other the anaerobic pathway."} {"id": "PMID:170248", "title": "Metabolism of cyclic adenosine 3',5'-monophosphate and induction of tryptophanase in Escherichia coli.", "content": "The relationship between cyclic adenosine 3',5'-monophosphate (cyclic AMP) metabolism and the induction of tryptophanase and beta-galactosidase was studied in several strains of Escherichia coli grown with succinate, acetate, glycerol, or glucose as the carbon source. No consistent relationship between the intracellular concentration of cyclic AMP in the several strains cultured and the various carbon sources was discerned. In E. coli K-12-1 the induction of tryptophanase was found to vary in the order: succinate greater than acetate greater than glycerol greater than glucose, and that of beta-galactosidase was found in the order: glycerol greater than acetate greater than succinate greater than glucose. Rate of accumulation of cyclic AMP in the culture filtrate was in the order: succinate greater than acetate greater than glycerol greater than glucose. The addition of glycerol to E. coli K-12-1 grown in acetate caused inhibition of tryptophanase and slight inhibition of accumulation of extracellular cyclic AMP. These same conditions caused beta-galactosidase induction to be stimulated. The addition of exogenous cyclic AMP to cultures grown with four different carbon sources had an effect characteristic for each of the two enzymes studied as well as each individual carbon source. The results suggest that there are control elements distinct from cyclic AMP and its receptor protein which respond to the catabolic situation of the cell.", "contents": "Metabolism of cyclic adenosine 3',5'-monophosphate and induction of tryptophanase in Escherichia coli. The relationship between cyclic adenosine 3',5'-monophosphate (cyclic AMP) metabolism and the induction of tryptophanase and beta-galactosidase was studied in several strains of Escherichia coli grown with succinate, acetate, glycerol, or glucose as the carbon source. No consistent relationship between the intracellular concentration of cyclic AMP in the several strains cultured and the various carbon sources was discerned. In E. coli K-12-1 the induction of tryptophanase was found to vary in the order: succinate greater than acetate greater than glycerol greater than glucose, and that of beta-galactosidase was found in the order: glycerol greater than acetate greater than succinate greater than glucose. Rate of accumulation of cyclic AMP in the culture filtrate was in the order: succinate greater than acetate greater than glycerol greater than glucose. The addition of glycerol to E. coli K-12-1 grown in acetate caused inhibition of tryptophanase and slight inhibition of accumulation of extracellular cyclic AMP. These same conditions caused beta-galactosidase induction to be stimulated. The addition of exogenous cyclic AMP to cultures grown with four different carbon sources had an effect characteristic for each of the two enzymes studied as well as each individual carbon source. The results suggest that there are control elements distinct from cyclic AMP and its receptor protein which respond to the catabolic situation of the cell."} {"id": "PMID:170249", "title": "Inhibition of growth by erythritol catabolism in Brucella abortus.", "content": "The growth of Brucella abortus (US-19) in a complex tryptose-yeast extract medium containing D-glucose is inhibited by 10 mM erythritol. The enzymes of the erythritol pathway, except for D-erythrulose 1-phosphate dehydrogenase (D-glycero-2-tetrulose 1-phosphate:nicotinamide adenine dinucleotide (NAD+) 4-oxidoreductase) were detected in the soluble and membrane fractions of cell extracts. Glucose catabolism by cell extracts was inhibited by erythritol, whereas, phosphorylated intermediates of the hexose monophosphate pathway were converted to pyruvic acid with oxygen consumption. Erythritol kinase (EC 2.7.1.27; adenosine 5'-triphosphate (ATP): erythritol 1-phosphotransferase) was found to be eightfold higher in activity than the hexokinase in cell extracts. In vivo, ATP is apparently consumed with the accumulation of D-erythrulose 1-phosphate (D-glycero-2-tetrulose 1-phosphate) and no substrate level phosphorylation. ATP levels dropped 10-fold in 30 min after addition of erythritol to log phase cells in tryptose-yeast extract medium with D-glucose as the carbon source. These data suggest bacteriostasis in the presence of erythritol results from the ATP drain caused by erythritol kinase.", "contents": "Inhibition of growth by erythritol catabolism in Brucella abortus. The growth of Brucella abortus (US-19) in a complex tryptose-yeast extract medium containing D-glucose is inhibited by 10 mM erythritol. The enzymes of the erythritol pathway, except for D-erythrulose 1-phosphate dehydrogenase (D-glycero-2-tetrulose 1-phosphate:nicotinamide adenine dinucleotide (NAD+) 4-oxidoreductase) were detected in the soluble and membrane fractions of cell extracts. Glucose catabolism by cell extracts was inhibited by erythritol, whereas, phosphorylated intermediates of the hexose monophosphate pathway were converted to pyruvic acid with oxygen consumption. Erythritol kinase (EC 2.7.1.27; adenosine 5'-triphosphate (ATP): erythritol 1-phosphotransferase) was found to be eightfold higher in activity than the hexokinase in cell extracts. In vivo, ATP is apparently consumed with the accumulation of D-erythrulose 1-phosphate (D-glycero-2-tetrulose 1-phosphate) and no substrate level phosphorylation. ATP levels dropped 10-fold in 30 min after addition of erythritol to log phase cells in tryptose-yeast extract medium with D-glucose as the carbon source. These data suggest bacteriostasis in the presence of erythritol results from the ATP drain caused by erythritol kinase."} {"id": "PMID:170250", "title": "CO2 production from galactose in galactose-1-phosphate uridyl transferase-deficient Escherichia coli.", "content": "Escherichia coli K-12 deficient in galactose-1-phosphate uridyl transferase is capable of converting significant amounts of d-[1-(14)C]galactose to (14)CO(2), whereas strains deficient in other enzymes of the Leloir pathway cannot do so.", "contents": "CO2 production from galactose in galactose-1-phosphate uridyl transferase-deficient Escherichia coli. Escherichia coli K-12 deficient in galactose-1-phosphate uridyl transferase is capable of converting significant amounts of d-[1-(14)C]galactose to (14)CO(2), whereas strains deficient in other enzymes of the Leloir pathway cannot do so."} {"id": "PMID:170251", "title": "Mutants defective in binding activity for cyclic adenosine 3',5'-monophosphate in Vibrio parahaemolyticus.", "content": "Mutants of Vibrio parahaemolyticus defective in binding activity for adenosine 3',5'-cyclic monophosphate are described. They were selected with medium containing the nucleotide together with starch.", "contents": "Mutants defective in binding activity for cyclic adenosine 3',5'-monophosphate in Vibrio parahaemolyticus. Mutants of Vibrio parahaemolyticus defective in binding activity for adenosine 3',5'-cyclic monophosphate are described. They were selected with medium containing the nucleotide together with starch."} {"id": "PMID:170252", "title": "Role for deoxyribonucleic acid ligase in deoxyribonucleic acid polymerase i-dependent repair synthesis in toluene-treated escherichia coli.", "content": "In a toluene-treated mutant of Escherichia coli K-12 having a temperature-sensitive, conditionally lethal mutation in the structural gene for deoxyribonucleic acid (DNA) ligase, an extensive DNA repair synthesis occurred in X-irradiated cells at the nonpermissive temperature, 42 C. At the permissive temperature, 30 C, nearly normal semiconservative synthesis and limited repair synthesis were observed when DNA ligase was activated by the addition of nicotinamide adenine dinucleotide.", "contents": "Role for deoxyribonucleic acid ligase in deoxyribonucleic acid polymerase i-dependent repair synthesis in toluene-treated escherichia coli. In a toluene-treated mutant of Escherichia coli K-12 having a temperature-sensitive, conditionally lethal mutation in the structural gene for deoxyribonucleic acid (DNA) ligase, an extensive DNA repair synthesis occurred in X-irradiated cells at the nonpermissive temperature, 42 C. At the permissive temperature, 30 C, nearly normal semiconservative synthesis and limited repair synthesis were observed when DNA ligase was activated by the addition of nicotinamide adenine dinucleotide."} {"id": "PMID:170253", "title": "Induction of alpha-glucosidase and synthesis during the cell cycle of Myxobacter AL-1.", "content": "Alpha-Glucosidase of Myxobacter AL-1 was induced by the addition of maltose to a defined medium as the sole carbon source. This induction takes place during lag-phase conditions without concomitant growth; it seems not to be regulated by the mechanism of catabolite repression. Using the method of density labeling with deuterated amino acids and subsequent analysis by equilibrium density gradient centrifugation in metrizamide-2H2O gradients it could be shown that the activity increase of the enzyme during induction is the the result of a de novo synthesis of the enzyme protein. After a short pulse of induction with maltose, alpha-glucosidase exhibited a pattern of variation in enzyme activity during the cell cycle that was similar to the one observed after growth of the cells on maltose for several generations.", "contents": "Induction of alpha-glucosidase and synthesis during the cell cycle of Myxobacter AL-1. Alpha-Glucosidase of Myxobacter AL-1 was induced by the addition of maltose to a defined medium as the sole carbon source. This induction takes place during lag-phase conditions without concomitant growth; it seems not to be regulated by the mechanism of catabolite repression. Using the method of density labeling with deuterated amino acids and subsequent analysis by equilibrium density gradient centrifugation in metrizamide-2H2O gradients it could be shown that the activity increase of the enzyme during induction is the the result of a de novo synthesis of the enzyme protein. After a short pulse of induction with maltose, alpha-glucosidase exhibited a pattern of variation in enzyme activity during the cell cycle that was similar to the one observed after growth of the cells on maltose for several generations."} {"id": "PMID:170256", "title": "Induction of phosphodiesterase by cyclic adenosine 3':5'-monophosphate in differentiating Dictyostelium discoideum amoebae.", "content": "Cyclic adenosine 3':5'-monophosphate added to the starvation media of Dictyostelium discoideum amoebae induces both intracellular and extracellular phosphodiesterase activities of these cells. The induced enzyme activity appears several hours earlier than that in starved cells which have not been induced with cyclic nucleotide. In both cases, the appearance of enzyme is inhibited by cycloheximide, and actinomycin D, and daunomycin. The KmS for the extracellular enzyme(s) of nucleotide-induced and uninduced control cells are identical. The induction of enzyme activity seems specific for cyclic adenosine 3':5'-monophosphate since cyclic guanosine 3':5'-monophosphate, as well as other nucleotides, have no effect. No differences in the activity or excretion of either N-acetylglucosaminidase or the inhibitory of the extracellular phosphodiesterase are observed between cyclic adenosine 3':5'-monophosphate-induced and control cells. A direct activation of phosphodiesterase by cyclic adenosine 3':5'-monophosphate can be excluded, since the addition of this nucleotide to cell lysates has no effect on the enzyme activity.", "contents": "Induction of phosphodiesterase by cyclic adenosine 3':5'-monophosphate in differentiating Dictyostelium discoideum amoebae. Cyclic adenosine 3':5'-monophosphate added to the starvation media of Dictyostelium discoideum amoebae induces both intracellular and extracellular phosphodiesterase activities of these cells. The induced enzyme activity appears several hours earlier than that in starved cells which have not been induced with cyclic nucleotide. In both cases, the appearance of enzyme is inhibited by cycloheximide, and actinomycin D, and daunomycin. The KmS for the extracellular enzyme(s) of nucleotide-induced and uninduced control cells are identical. The induction of enzyme activity seems specific for cyclic adenosine 3':5'-monophosphate since cyclic guanosine 3':5'-monophosphate, as well as other nucleotides, have no effect. No differences in the activity or excretion of either N-acetylglucosaminidase or the inhibitory of the extracellular phosphodiesterase are observed between cyclic adenosine 3':5'-monophosphate-induced and control cells. A direct activation of phosphodiesterase by cyclic adenosine 3':5'-monophosphate can be excluded, since the addition of this nucleotide to cell lysates has no effect on the enzyme activity."} {"id": "PMID:170257", "title": "A comparative study on the removal of cellular lipids from Landsch\u00fctz ascites cells by human plasma apolipoproteins.", "content": "The effects of human plasma lipoprotein-proteins on the removal of cellular lipids from Landsch\u00fctz ascites cells were studied. Cellular lipids were labeled by injecting mice previously injected with ascites with either [3H]cholesterol or [3H]choline. Apoproteins from very low density (apoC-I, C-II, and C-111) and high density (apoA-I and A-II) lipoproteins were used. Each of the apoproteins alone was ineffective in removing cellular [3H]cholesterol. However, when synthetic phosphatidylcholines of known composition were added to each apoprotein and the experiments were repeated using either apoprotein-lipid mixtures or ultracentrifugally isolated complexes, the removal of sterol was considerably enhanced. Complexes of saturated phosphatidylcholines with apoA-II, apoC-I, or apoC-III were the most effective in releasing cellular sterol. Apoprotein-phospholipid complexes were much less effective in removing cellular [3H]phosphatidylcholine than the free apoproteins; apoA-I and apoC-I were the best of the five apoproteins studied. When a comparison was made of the adsorption of iodinated apoproteins to ascites cells, 3 to 4 times more apoA-II and apoC-III were bound than apoA-I. The binding of apoproteins was time and temperature dependent. Approximately 50% of the radioactivity that remained in the washed cells was removed with trypsin. To determine if the counts remaining in the trypsin-treated cells were internalized, identical experiments were performed using human erythrocytes, cells that do not exhibit pinocytosis. Again, approximately 50% of the radioactivity of the iodinated apoproteins was not released by trypsin. Succinylation of apoA-II not only destroys its phospholipid-binding properties but also its adsorption to red cells. These results suggest that the plasma apoproteins differ in their ability to remove cellular lipids and bind to both ascites and red cell membranes, and possibly to specific phospholipids, in such a way that only a part of the apoprotein is degraded with proteases.", "contents": "A comparative study on the removal of cellular lipids from Landsch\u00fctz ascites cells by human plasma apolipoproteins. The effects of human plasma lipoprotein-proteins on the removal of cellular lipids from Landsch\u00fctz ascites cells were studied. Cellular lipids were labeled by injecting mice previously injected with ascites with either [3H]cholesterol or [3H]choline. Apoproteins from very low density (apoC-I, C-II, and C-111) and high density (apoA-I and A-II) lipoproteins were used. Each of the apoproteins alone was ineffective in removing cellular [3H]cholesterol. However, when synthetic phosphatidylcholines of known composition were added to each apoprotein and the experiments were repeated using either apoprotein-lipid mixtures or ultracentrifugally isolated complexes, the removal of sterol was considerably enhanced. Complexes of saturated phosphatidylcholines with apoA-II, apoC-I, or apoC-III were the most effective in releasing cellular sterol. Apoprotein-phospholipid complexes were much less effective in removing cellular [3H]phosphatidylcholine than the free apoproteins; apoA-I and apoC-I were the best of the five apoproteins studied. When a comparison was made of the adsorption of iodinated apoproteins to ascites cells, 3 to 4 times more apoA-II and apoC-III were bound than apoA-I. The binding of apoproteins was time and temperature dependent. Approximately 50% of the radioactivity that remained in the washed cells was removed with trypsin. To determine if the counts remaining in the trypsin-treated cells were internalized, identical experiments were performed using human erythrocytes, cells that do not exhibit pinocytosis. Again, approximately 50% of the radioactivity of the iodinated apoproteins was not released by trypsin. Succinylation of apoA-II not only destroys its phospholipid-binding properties but also its adsorption to red cells. These results suggest that the plasma apoproteins differ in their ability to remove cellular lipids and bind to both ascites and red cell membranes, and possibly to specific phospholipids, in such a way that only a part of the apoprotein is degraded with proteases."} {"id": "PMID:170258", "title": "Lactate dehydrogenase-catalyzed stereospecific hydrogen atom transfer from reduced nicotinamide adenine dinucleotide to dicarboxylate radicals.", "content": "The dicarboxylate radical -OOC--CH--CH(OH)COO- was generated in an N2O-saturated fumarate solution by high energy ionizing radiation. When NADH was present in the solution, product analysis indicated a stoichiometry of 2 molecules of the radical reacted with 1 NADH molecule to form 2 malate and 1 enzymatically active NAD+ molecules. In a similar experiment using tritium label on position A of NADH, due to an isotope effect, only 10% of the label was transferred to malate; most of the remaining tritium was found in the NAD+ formed. When lactate dehydrogenase was added, however, no la bel was detectable in NAD+, and over 80% of the tritium lost from NADH was found in malate. The stereospecific transfer of the hydrogen atom from lactate dehydrogenase-bound NADH to the dicarboxylate radical suggested that the free radical reaction must have taken place at the active site. The hydrogen atom transfer was inhibited by oxamate. Results from flow experiments in which an irradiated fumarate solution was mixed with a solutionof lactate dehydrogenase and NADH are in support of a mechanism in which the hydrogen atom transfer occurs in the first oxidation step.", "contents": "Lactate dehydrogenase-catalyzed stereospecific hydrogen atom transfer from reduced nicotinamide adenine dinucleotide to dicarboxylate radicals. The dicarboxylate radical -OOC--CH--CH(OH)COO- was generated in an N2O-saturated fumarate solution by high energy ionizing radiation. When NADH was present in the solution, product analysis indicated a stoichiometry of 2 molecules of the radical reacted with 1 NADH molecule to form 2 malate and 1 enzymatically active NAD+ molecules. In a similar experiment using tritium label on position A of NADH, due to an isotope effect, only 10% of the label was transferred to malate; most of the remaining tritium was found in the NAD+ formed. When lactate dehydrogenase was added, however, no la bel was detectable in NAD+, and over 80% of the tritium lost from NADH was found in malate. The stereospecific transfer of the hydrogen atom from lactate dehydrogenase-bound NADH to the dicarboxylate radical suggested that the free radical reaction must have taken place at the active site. The hydrogen atom transfer was inhibited by oxamate. Results from flow experiments in which an irradiated fumarate solution was mixed with a solutionof lactate dehydrogenase and NADH are in support of a mechanism in which the hydrogen atom transfer occurs in the first oxidation step."} {"id": "PMID:170259", "title": "The interaction of apoA-I from human high density lipoprotein with lysolecithin.", "content": "The binding of apoA-I to lysolecithin has been studied by fluorescence and circular dichroism. The influence of the conformation of apoA-I on its interaction with lysolecithin has also been evaluated. ApoA-I is bound to lysolecithin with an association greater than 10(7) whether apoA-I is native or highly unfolded in 1.8 M guanidinium hydrochloride. The association of apoA-I with lysolecithin results in an increase in secondary structure. A 25-residue fragment of apoA-I binds to lysolecithin equally strongly as the native molecule.", "contents": "The interaction of apoA-I from human high density lipoprotein with lysolecithin. The binding of apoA-I to lysolecithin has been studied by fluorescence and circular dichroism. The influence of the conformation of apoA-I on its interaction with lysolecithin has also been evaluated. ApoA-I is bound to lysolecithin with an association greater than 10(7) whether apoA-I is native or highly unfolded in 1.8 M guanidinium hydrochloride. The association of apoA-I with lysolecithin results in an increase in secondary structure. A 25-residue fragment of apoA-I binds to lysolecithin equally strongly as the native molecule."} {"id": "PMID:170260", "title": "A novel oligoribonuclease of Escherichia coli. II. Mechanism of action.", "content": "Detailed studies of the mechanism of action of the novel oligoribonuclease of Escherichia coli described in the previous paper (1) led to the following conclusions. 1. The enzyme prefers a free 3'-hydroxyl group for its action. 2. The enzyme attacks the oligoribonucleotide substrate in a sequential manner from the 3' end producing 5'-ribonucleotides. 3. The mode of attack appears to be processive; the enzyme acts by degrading one oligoribonucleotide chain to completion before proceeding to the hydrolysis of another chain. 4. The reaction rate is inversely proportional to the chain length of the substrate; however, the enzyme has a higher affinity for longer chains. 5. The enzyme activity is markedly inhibited by secondary structure; oligoribonucleotides combined with complementary polyribonucleotides are attacked poorly below the melting temperature of the complex and efficiently above the melting temperature. 6. The enzyme is inhibited by 5'-nucleotides of adenine and guanine; those of cytosine and uracil have a much smaller effect. The enzyme is not inhibited by 3'-nucleotides. 7. Studies with dinucleoside monophosphate show highest reaction rates with pyrimidine sequences in the order: CpCgreater than UpUgreater than CpUgreater than UpC. The presence of guanine at the 3' end is strongly inhibitory, and reaction rates are CpGgreater than UpG=ApGgreater than GpG.", "contents": "A novel oligoribonuclease of Escherichia coli. II. Mechanism of action. Detailed studies of the mechanism of action of the novel oligoribonuclease of Escherichia coli described in the previous paper (1) led to the following conclusions. 1. The enzyme prefers a free 3'-hydroxyl group for its action. 2. The enzyme attacks the oligoribonucleotide substrate in a sequential manner from the 3' end producing 5'-ribonucleotides. 3. The mode of attack appears to be processive; the enzyme acts by degrading one oligoribonucleotide chain to completion before proceeding to the hydrolysis of another chain. 4. The reaction rate is inversely proportional to the chain length of the substrate; however, the enzyme has a higher affinity for longer chains. 5. The enzyme activity is markedly inhibited by secondary structure; oligoribonucleotides combined with complementary polyribonucleotides are attacked poorly below the melting temperature of the complex and efficiently above the melting temperature. 6. The enzyme is inhibited by 5'-nucleotides of adenine and guanine; those of cytosine and uracil have a much smaller effect. The enzyme is not inhibited by 3'-nucleotides. 7. Studies with dinucleoside monophosphate show highest reaction rates with pyrimidine sequences in the order: CpCgreater than UpUgreater than CpUgreater than UpC. The presence of guanine at the 3' end is strongly inhibitory, and reaction rates are CpGgreater than UpG=ApGgreater than GpG."} {"id": "PMID:170261", "title": "Partial purification and properties of guanosine 3':5'-monophosphate-dependent protein kinase from pig lung.", "content": "Guanosine 3':5'-monophosphate(cyclic GMP)-dependent protein kinase which catalyzes the phosphorylation of histone was purified about 200-fold from the soluble fraction of pig lung by pH 5.5 precipitation, DEAE-cellulose column chromatography, and Sephadex G-200 gel filtration. The apparent Ka values for guanosine 3':5'-monophosphate and adenosine 3':5'-monophosphate were determined to be about 17 and 360 nM, respectively. Mg2+ was essential for the activity exhibiting biphasic stimulation behavior and neither Mn2+ nor Ca2+ could substitute for Mg2+. However, these divalent ions markedly inhibited the protein kinase activity stimulated by cyclic GMP in the presence of Mg2+.", "contents": "Partial purification and properties of guanosine 3':5'-monophosphate-dependent protein kinase from pig lung. Guanosine 3':5'-monophosphate(cyclic GMP)-dependent protein kinase which catalyzes the phosphorylation of histone was purified about 200-fold from the soluble fraction of pig lung by pH 5.5 precipitation, DEAE-cellulose column chromatography, and Sephadex G-200 gel filtration. The apparent Ka values for guanosine 3':5'-monophosphate and adenosine 3':5'-monophosphate were determined to be about 17 and 360 nM, respectively. Mg2+ was essential for the activity exhibiting biphasic stimulation behavior and neither Mn2+ nor Ca2+ could substitute for Mg2+. However, these divalent ions markedly inhibited the protein kinase activity stimulated by cyclic GMP in the presence of Mg2+."} {"id": "PMID:170262", "title": "Studies of the quaternary structure and the chemical properties of phosphoribosylpyrophosphate synthetase from Salmonella typhimurium.", "content": "Phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1) was purified to virtual homogeneity from Salmonella typhimurium cells by a modification of previously published procedures. The molecular weight of the subunit was determined to be 31,000 +/- 3,000 by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium analysis of the enzyme dissolved in 6 M guanidine hydrochloride. The amino acid composition of the enzyme was determined. Proline was identified as the only NH2-terminal residue. PRPP synthetase is apparently composed of identical or nearly identical subunits. NATIVE PRPP synthetase exists in multiple states of aggregation under all conditions. However, two predominant states were demonstrated under certain conditions. A form with molecular weight of 320,000 +/- 20,000 was found at pH 7.5 in the presence of MgATP. At pH 8.2 to 8.6, with or without MgATP, the predominant form corresponded to a molecular weight of 150,000 to 200,000; sedimentation equilibrium and velocity analysis indicated 160,000 +/- 15,000 as the most reliable molecular weight. More highly aggregated forms were observed at 4 degrees and higher protein concentrations. Removal of inorganic phosphate from PRPP synthetase by dilution or dialysis resulted in disaggregation. The fundamental unit of PRPP synthetase appears to consist of five (or possibly six) subunits, which can associate to form a dimer (10 or 12 subunits) and more highly aggregated forms. A pentameric subunit structure is consistent with the multiple species resolved by electrophoresis of the native enzyme in discontinuous polyacrylamide gel systems. Visualization of PRPP synthetase by negative staining with uranyl acetate and electron microscopy revealed fields of very asymmetric molecules, the dimensions of which corresponded to the M = 160,000 form. Dimers and higher aggregates of this unit were also seen. An unusual model, in which the five subunits are asymmetrically arranged, accounts very well for the electron microscopic appearance of the enzyme. The tendency of the enzyme to aggregate is viewed as a consequence of the unsatisfied bonding regions of the fundamental asymmetric unit.", "contents": "Studies of the quaternary structure and the chemical properties of phosphoribosylpyrophosphate synthetase from Salmonella typhimurium. Phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1) was purified to virtual homogeneity from Salmonella typhimurium cells by a modification of previously published procedures. The molecular weight of the subunit was determined to be 31,000 +/- 3,000 by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium analysis of the enzyme dissolved in 6 M guanidine hydrochloride. The amino acid composition of the enzyme was determined. Proline was identified as the only NH2-terminal residue. PRPP synthetase is apparently composed of identical or nearly identical subunits. NATIVE PRPP synthetase exists in multiple states of aggregation under all conditions. However, two predominant states were demonstrated under certain conditions. A form with molecular weight of 320,000 +/- 20,000 was found at pH 7.5 in the presence of MgATP. At pH 8.2 to 8.6, with or without MgATP, the predominant form corresponded to a molecular weight of 150,000 to 200,000; sedimentation equilibrium and velocity analysis indicated 160,000 +/- 15,000 as the most reliable molecular weight. More highly aggregated forms were observed at 4 degrees and higher protein concentrations. Removal of inorganic phosphate from PRPP synthetase by dilution or dialysis resulted in disaggregation. The fundamental unit of PRPP synthetase appears to consist of five (or possibly six) subunits, which can associate to form a dimer (10 or 12 subunits) and more highly aggregated forms. A pentameric subunit structure is consistent with the multiple species resolved by electrophoresis of the native enzyme in discontinuous polyacrylamide gel systems. Visualization of PRPP synthetase by negative staining with uranyl acetate and electron microscopy revealed fields of very asymmetric molecules, the dimensions of which corresponded to the M = 160,000 form. Dimers and higher aggregates of this unit were also seen. An unusual model, in which the five subunits are asymmetrically arranged, accounts very well for the electron microscopic appearance of the enzyme. The tendency of the enzyme to aggregate is viewed as a consequence of the unsatisfied bonding regions of the fundamental asymmetric unit."} {"id": "PMID:170263", "title": "The stereospecificity of the enzymic reduction of 21-dehydrocortisol by NADH.", "content": "(21R)-[21-3H]cortisol and (21S)-[21-3H]cortisol were synthesized by reduction of 21-dehydrocortisol by NADH in the presence of 21-hydroxysteroid dehydrogenase. The stereochemistry at carbon 21 was established after cleaving the side chain and oxidizing the resulting two epimers of tritiated glycolate with glycolate oxidase of known (2-pro-S) stereospecificity. From the distribution of radioactivity in the water and glyoxylate produced in this reaction, it was concluded that the reaction of 21-dehydrocortisol with (4S)-[4-3H]NADH catalyzed by 21-hydroxysteroid dehydrogenase results in a transfer of tritium from the 4S position of the nucleotide to form (21S)-[21-3H]cortisol, and that (21R)-[21-3H]cortisol resulted from the enzyme-catalyzed reduction of 21-dehydro[21-3H]cortisol with NADH. Nuclear magnetic resonance studies on both epimers at position 21 of [21-2H]cortisol and of [21-2H]cortisone prepared enzymically identify the transferring 21-pro-S hydrogen as the relatively downfield of the two 21-hydrogen atoms.", "contents": "The stereospecificity of the enzymic reduction of 21-dehydrocortisol by NADH. (21R)-[21-3H]cortisol and (21S)-[21-3H]cortisol were synthesized by reduction of 21-dehydrocortisol by NADH in the presence of 21-hydroxysteroid dehydrogenase. The stereochemistry at carbon 21 was established after cleaving the side chain and oxidizing the resulting two epimers of tritiated glycolate with glycolate oxidase of known (2-pro-S) stereospecificity. From the distribution of radioactivity in the water and glyoxylate produced in this reaction, it was concluded that the reaction of 21-dehydrocortisol with (4S)-[4-3H]NADH catalyzed by 21-hydroxysteroid dehydrogenase results in a transfer of tritium from the 4S position of the nucleotide to form (21S)-[21-3H]cortisol, and that (21R)-[21-3H]cortisol resulted from the enzyme-catalyzed reduction of 21-dehydro[21-3H]cortisol with NADH. Nuclear magnetic resonance studies on both epimers at position 21 of [21-2H]cortisol and of [21-2H]cortisone prepared enzymically identify the transferring 21-pro-S hydrogen as the relatively downfield of the two 21-hydrogen atoms."} {"id": "PMID:170264", "title": "Solubilization of calcitonin-responsive renal cortical adenylate cyclase.", "content": "Purification of pork renal cortex membranes yielded a particulate adenylate cyclase retaining good sensitivity to stimulation by parathyroid hormone and glucagon and a modest but significant response to porcine calcitonin. Treatment of this partially purified membrane fraction with 0.5% Lubrol PX and 5 mM NaF released adenylate cyclase activity into a fraction which was not sedimented by centrifugation for 20 min at 37,000 X g or for 2 hours at 100,000 X g and passed through a Millipore filter (0.22 mum pore). This solubilized adenylate cyclase was stimulated by porcine calcitonin and NaF but not by parathyroid hormone or glucagon. On gel filtration (Sephadex G-200) in the presence of 1mM dithiothreitol and 5mM NaF, the major portion of the adenylate cyclase activity eluted with the void volume of the column and showed 2.0-fold stimulation with 10 muM calcitonin. Binding of 125I-labeled porcine calcitonin was demonstrated in the 37,000 X g and the 100,000 X g supernatants. From 74 to 86% of the observed binding could be blocked by the addition of unlabeled porcine calcitonin to the reaction mixture. Addition of salmon calcitonin, parathyroid hormone, or glucagon blocked only 12 to 18% of the binding. The dose-response curves for inhibition of binding of iodinated calcitonin by unlabeled calcitonin and the activation of adenylate cyclase by the hormone each showed 50% maximal effect at a concentration between 4.5 and 8 muM porcine calcitonin and maximal effect at a concentration between 33 and 66 muM porcine calcitonin.", "contents": "Solubilization of calcitonin-responsive renal cortical adenylate cyclase. Purification of pork renal cortex membranes yielded a particulate adenylate cyclase retaining good sensitivity to stimulation by parathyroid hormone and glucagon and a modest but significant response to porcine calcitonin. Treatment of this partially purified membrane fraction with 0.5% Lubrol PX and 5 mM NaF released adenylate cyclase activity into a fraction which was not sedimented by centrifugation for 20 min at 37,000 X g or for 2 hours at 100,000 X g and passed through a Millipore filter (0.22 mum pore). This solubilized adenylate cyclase was stimulated by porcine calcitonin and NaF but not by parathyroid hormone or glucagon. On gel filtration (Sephadex G-200) in the presence of 1mM dithiothreitol and 5mM NaF, the major portion of the adenylate cyclase activity eluted with the void volume of the column and showed 2.0-fold stimulation with 10 muM calcitonin. Binding of 125I-labeled porcine calcitonin was demonstrated in the 37,000 X g and the 100,000 X g supernatants. From 74 to 86% of the observed binding could be blocked by the addition of unlabeled porcine calcitonin to the reaction mixture. Addition of salmon calcitonin, parathyroid hormone, or glucagon blocked only 12 to 18% of the binding. The dose-response curves for inhibition of binding of iodinated calcitonin by unlabeled calcitonin and the activation of adenylate cyclase by the hormone each showed 50% maximal effect at a concentration between 4.5 and 8 muM porcine calcitonin and maximal effect at a concentration between 33 and 66 muM porcine calcitonin."} {"id": "PMID:170265", "title": "Regulation of intracellular adenosine cyclic 3':5'-monophosphate levels in Escherichia coli and Salmonella typhimurium. Evidence for energy-dependent excretion of the cyclic nucleotide.", "content": "Sugars and other energy sources were found to lower intracellular concentrations of adenosine 3':5'-monophosphate (cyclic AMP) in strains of Escherichia coli and Salmonella typhimurium which were deficient for cyclic AMP phosphodiesterase. This effect required the presence of the specific transport system responsible for entry of that sugar into the cell and depended on the intracellular catabolic enzymes. Metabolizable sugars were more effective than nonmetabolizable sugars in reducing cellular cyclic AMP levels, and this reduction was blocked partially by uncouplers of oxidative phosphorylation. Electron donors such as lactate and ascorbate plus phenazine methosulfate reduced internal cyclic AMP levels in bacterial membrane vesicles which had been preloaded with the cyclic nucleotide. Uncouplers of oxidative phosphorylation, but not arsenate, blocked the energy-stimulated loss of intravesicular cyclic AMP. Employing intact cells, sugars were shown to have two primary effects on cyclic AMP metabolism: (a) they inhibited net synthesis of the cyclic nucleotide while promoting its degradation, and (b) they stimulated efflux of cyclic AMP into the extracellular fluid. While the former effect was elicited by metabolizable and nonmetabolizable sugars alike, stimulation of cyclic nucleotide excretion was only observed with metabolizable sugars. The results suggest that the extrusion of cyclic AMP from the bacterial cell is energy-dependent and is driven by an energized membrane state.", "contents": "Regulation of intracellular adenosine cyclic 3':5'-monophosphate levels in Escherichia coli and Salmonella typhimurium. Evidence for energy-dependent excretion of the cyclic nucleotide. Sugars and other energy sources were found to lower intracellular concentrations of adenosine 3':5'-monophosphate (cyclic AMP) in strains of Escherichia coli and Salmonella typhimurium which were deficient for cyclic AMP phosphodiesterase. This effect required the presence of the specific transport system responsible for entry of that sugar into the cell and depended on the intracellular catabolic enzymes. Metabolizable sugars were more effective than nonmetabolizable sugars in reducing cellular cyclic AMP levels, and this reduction was blocked partially by uncouplers of oxidative phosphorylation. Electron donors such as lactate and ascorbate plus phenazine methosulfate reduced internal cyclic AMP levels in bacterial membrane vesicles which had been preloaded with the cyclic nucleotide. Uncouplers of oxidative phosphorylation, but not arsenate, blocked the energy-stimulated loss of intravesicular cyclic AMP. Employing intact cells, sugars were shown to have two primary effects on cyclic AMP metabolism: (a) they inhibited net synthesis of the cyclic nucleotide while promoting its degradation, and (b) they stimulated efflux of cyclic AMP into the extracellular fluid. While the former effect was elicited by metabolizable and nonmetabolizable sugars alike, stimulation of cyclic nucleotide excretion was only observed with metabolizable sugars. The results suggest that the extrusion of cyclic AMP from the bacterial cell is energy-dependent and is driven by an energized membrane state."} {"id": "PMID:170266", "title": "Heme A of cytochrome c oxicase. Structure and properties: comparisons with hemes B, C, and S and derivatives.", "content": "Heme A, isolated from bovine heart muscle by procedures which include extractions into pyridine/chloroform and two-phase, liquid-liquid chromatography on Celite, has been converted to several derivatives. Examination of the proton nuclear magnetic resonance (PMR) spectra and other properties of these derivatives reveals heme A to be the iron complex of 8-formyl-6,-m-bis(2''-hydroxycarbonylethyl)-2-(1'-hydroxy-5',9',13'-trimethyl-4',8',12'-trans,trans-tetradecatrienyl)-1,3,5-trimethyl-4-vinylporphin. Substituents at the 2,4, and 8 positions are replaced by hydrogen in a resorcinol melt to give cytodeuteroporphin (8-demethyldeuteroporphyrin IX)...", "contents": "Heme A of cytochrome c oxicase. Structure and properties: comparisons with hemes B, C, and S and derivatives. Heme A, isolated from bovine heart muscle by procedures which include extractions into pyridine/chloroform and two-phase, liquid-liquid chromatography on Celite, has been converted to several derivatives. Examination of the proton nuclear magnetic resonance (PMR) spectra and other properties of these derivatives reveals heme A to be the iron complex of 8-formyl-6,-m-bis(2''-hydroxycarbonylethyl)-2-(1'-hydroxy-5',9',13'-trimethyl-4',8',12'-trans,trans-tetradecatrienyl)-1,3,5-trimethyl-4-vinylporphin. Substituents at the 2,4, and 8 positions are replaced by hydrogen in a resorcinol melt to give cytodeuteroporphin (8-demethyldeuteroporphyrin IX)..."} {"id": "PMID:170267", "title": "Active site stoichiometry of L-phenylalanine: tRNA ligase from Escherichia coli K(-10).", "content": "The existence of two active siter per molecule of L-phenylalanine:tRNA ligase from Escherichia coli K(-10) has been demonstrated by isolation of the E-aminoacyl adenylate and tel filtration and the nitrocellulose filter assay at pH 5.0 revealed the same stoichiometry for the E-tRNAPhe comples as protection against degradation by snake venom phosphodiesterase and equilibrium gel filtration at pH 7.5. Using a fluorescence titration technique, it was found that the dissociation constant for ligase-tRNAPhe complex is decreased 20-fold when the hydrogen ion concentration is changed from pH 6.0 to pH 5.0. The existence of two active sites binding the aminoacyl adenylate intermediate was demonstrated by gel filtration and retention on DEAE-cellulose filters. \"Burst\" experiments indicated that two sites were involved in a rapid ATP consumption at conditions of catalytic amino acid activation. Furthermore, it was observed that the activated amino acid could be transferred from both sites to cognate tRNA.", "contents": "Active site stoichiometry of L-phenylalanine: tRNA ligase from Escherichia coli K(-10). The existence of two active siter per molecule of L-phenylalanine:tRNA ligase from Escherichia coli K(-10) has been demonstrated by isolation of the E-aminoacyl adenylate and tel filtration and the nitrocellulose filter assay at pH 5.0 revealed the same stoichiometry for the E-tRNAPhe comples as protection against degradation by snake venom phosphodiesterase and equilibrium gel filtration at pH 7.5. Using a fluorescence titration technique, it was found that the dissociation constant for ligase-tRNAPhe complex is decreased 20-fold when the hydrogen ion concentration is changed from pH 6.0 to pH 5.0. The existence of two active sites binding the aminoacyl adenylate intermediate was demonstrated by gel filtration and retention on DEAE-cellulose filters. \"Burst\" experiments indicated that two sites were involved in a rapid ATP consumption at conditions of catalytic amino acid activation. Furthermore, it was observed that the activated amino acid could be transferred from both sites to cognate tRNA."} {"id": "PMID:170268", "title": "Purification and characterization of shikimate kinase enzyme activity in Bacillus subtilis.", "content": "In Bacillus subtilis shikimate kinase enzyme activity can be demonstrated when a small polypeptide forms a trifunctional complex with the bifunctional enzyme 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase-chorismate mutase. The shikimate kinase polypeptide whoch carries the catalytic site has been purified to homogeneity by a five-step procedure. The skikimate kinase was determined to have a molecular weight of 10,000 by superfine Sephadex G-75 thin layer chromatography and by calculation of the minimum chemical molecular weight from its amino acid composition. This number corresponds closely to the molecular weight determined by the mobility of the protein following electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate. The enzyme aggregates with itself forming larger molecular weight proteins. Thes aggregational pattersn depend on protein concentration and sulfhydryl bridges. The enzyme activity is completely inhibited by EDTA and the requirement for Mg2+ can be partially replaced by Mn2+, Ca2+, and Co2+. The inhibition of shikimate kinase activity by p-hydroxymercuribenzoate is reversed completely when the enzyme complex is treated with dithiothreitol, suggesting the sulfhydryl groups may be involved with the active site. The trifunctional complex is relatively unstable, and the nonidentical subunits dissociate readily. This dissociation results in a 99% loss in shikimate kinase activity and a 30% decrease in the chorismate mutase-DAHP synthetase activities. Shikimate kinase activity is subject to a variety of controls. It is inhibited by the allosteric effectors chorismate and prephenate, the products of the reaction, ADP, and shikimate 5-phosphate. The activity responds to changes in the energy charge of the cell. Because of the variety of controls exerted on this enzyme, this member of the regulatory complex may represent the key enzyme in the allosteric control of the synthesis of the common precursors of aromatic acid synthesis.", "contents": "Purification and characterization of shikimate kinase enzyme activity in Bacillus subtilis. In Bacillus subtilis shikimate kinase enzyme activity can be demonstrated when a small polypeptide forms a trifunctional complex with the bifunctional enzyme 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase-chorismate mutase. The shikimate kinase polypeptide whoch carries the catalytic site has been purified to homogeneity by a five-step procedure. The skikimate kinase was determined to have a molecular weight of 10,000 by superfine Sephadex G-75 thin layer chromatography and by calculation of the minimum chemical molecular weight from its amino acid composition. This number corresponds closely to the molecular weight determined by the mobility of the protein following electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate. The enzyme aggregates with itself forming larger molecular weight proteins. Thes aggregational pattersn depend on protein concentration and sulfhydryl bridges. The enzyme activity is completely inhibited by EDTA and the requirement for Mg2+ can be partially replaced by Mn2+, Ca2+, and Co2+. The inhibition of shikimate kinase activity by p-hydroxymercuribenzoate is reversed completely when the enzyme complex is treated with dithiothreitol, suggesting the sulfhydryl groups may be involved with the active site. The trifunctional complex is relatively unstable, and the nonidentical subunits dissociate readily. This dissociation results in a 99% loss in shikimate kinase activity and a 30% decrease in the chorismate mutase-DAHP synthetase activities. Shikimate kinase activity is subject to a variety of controls. It is inhibited by the allosteric effectors chorismate and prephenate, the products of the reaction, ADP, and shikimate 5-phosphate. The activity responds to changes in the energy charge of the cell. Because of the variety of controls exerted on this enzyme, this member of the regulatory complex may represent the key enzyme in the allosteric control of the synthesis of the common precursors of aromatic acid synthesis."} {"id": "PMID:170269", "title": "Regulation of aryl hydrocarbon (benzo-(A)-pyrene) hydroxylase activity in mammalian cells. Induction of hydroxylase activity by N6,O2'-dibutyryl8 adenosine 3':5'-monophosphate and aminophylline.", "content": "Treatment of hamster BHK cells with N6,O2'-dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP), aminophylline, theophylline, or papaverine increased the level of aryl hydrocarbon (benzo(a)pyrene) hydrolxylase activity. The highese increase, 100-fold, was obtained with Bt2cAMP plus aminophylline or theophylline. N2,O2-Dibutyryl guanosine 3':5'-monophosphate gave a lower induction than Bt2cAMP. The level of hydroxylase activity started to decrease 6 hours after treatment with the inducer and was reduced to almost the uninduced level after 24 hours. Repeated addition of Bt2cAMP and aminophylline did not prevent this decrease. The hydroxylase can also be induced by treating cells with benz(a)anthracene, and the level of this induced activity was maintained for 24 hours. Aminophylline gave a 2- to 8-fold stimulation of the induction by benz(a)anthracene. The enzyme activity induced by Bt2cAMP, aminophylline, and benz(a)anthracene converted benzo(a)pyrene to similar alkali-extractable metabolities with a fluorescence spectra similar to that of 3-hydroxybenzo(a)pyrene. These induced enzyme activities also showed a similar heat stability. Induction by Bt2cAMP and aminophylline, like induction by benz(a)anthracene, required continued protein synthesis and only an initial period of RNA synthesis. Compared to the benz(a)anthracene-induced hydroxylase with a Km of 4.3 muM, the hydroxylase induced by Bt2cAMP and aminophylline showed a Km of 0.14 muM, and was 100-fold more sensitive to inhibition by 7,8-benzoflavone. Increasing the serum concentration in the culture medium stimulated the induction by aminophylline but did not stimulate induction by benz(a)anthracene. The results indicate that aryl hydrocaarbon (benzo(a)pyrene) hydroxylase can be induced by compounds that increase the level of adenosine 3':5'-monophosphate and that this induction and induced enzyme activity differs from that caused by benz(a)anthracene.", "contents": "Regulation of aryl hydrocarbon (benzo-(A)-pyrene) hydroxylase activity in mammalian cells. Induction of hydroxylase activity by N6,O2'-dibutyryl8 adenosine 3':5'-monophosphate and aminophylline. Treatment of hamster BHK cells with N6,O2'-dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP), aminophylline, theophylline, or papaverine increased the level of aryl hydrocarbon (benzo(a)pyrene) hydrolxylase activity. The highese increase, 100-fold, was obtained with Bt2cAMP plus aminophylline or theophylline. N2,O2-Dibutyryl guanosine 3':5'-monophosphate gave a lower induction than Bt2cAMP. The level of hydroxylase activity started to decrease 6 hours after treatment with the inducer and was reduced to almost the uninduced level after 24 hours. Repeated addition of Bt2cAMP and aminophylline did not prevent this decrease. The hydroxylase can also be induced by treating cells with benz(a)anthracene, and the level of this induced activity was maintained for 24 hours. Aminophylline gave a 2- to 8-fold stimulation of the induction by benz(a)anthracene. The enzyme activity induced by Bt2cAMP, aminophylline, and benz(a)anthracene converted benzo(a)pyrene to similar alkali-extractable metabolities with a fluorescence spectra similar to that of 3-hydroxybenzo(a)pyrene. These induced enzyme activities also showed a similar heat stability. Induction by Bt2cAMP and aminophylline, like induction by benz(a)anthracene, required continued protein synthesis and only an initial period of RNA synthesis. Compared to the benz(a)anthracene-induced hydroxylase with a Km of 4.3 muM, the hydroxylase induced by Bt2cAMP and aminophylline showed a Km of 0.14 muM, and was 100-fold more sensitive to inhibition by 7,8-benzoflavone. Increasing the serum concentration in the culture medium stimulated the induction by aminophylline but did not stimulate induction by benz(a)anthracene. The results indicate that aryl hydrocaarbon (benzo(a)pyrene) hydroxylase can be induced by compounds that increase the level of adenosine 3':5'-monophosphate and that this induction and induced enzyme activity differs from that caused by benz(a)anthracene."} {"id": "PMID:170270", "title": "Comparison of adenosine 3':5'-monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle.", "content": "Homogeneous preparations of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase from rabbit skeletal (Peak I) and bovine heart muscle have been compared. Each enzyme has an S20,w value of 7.0. Each enzyme binds 2 mol of cyclic AMP per mol of enzyme and is dissociated in the presence of saturating concentrations of cyclic AMP into a demeric regulatory subunit-cyclic AMP complex and two catalytic subunits. The isolated subunits recombine, resulting in the formation of the original holoenzyme in each case. Several differences between the two enzymes were found. Different salt concentrations are necessary for elution of the respective enzyme from DEAE-cellulose. Their regulatory subunits differ with respect to their sedimentation constants and mobility on sodium dodecyl sulfate gel electrophoresis. The regulatory subunit of the heart enzyme is rapidly phosphorylated by MgATP but this does not occur with the skeletal muscle enzyme. MgATP is bound with high affinity only to the skeletal muscle enzyme. The enzymes have different apparent dissociation constants and Hill coefficients for cyclic AMP binding. With the skeletal muscle enzyme MgATP increases the dissociation constants for cyclic AMP about 10-fold and decreases the Hill coefficient, while with the heart enzyme phosphorylation decreases the cissociation constant for cyclic AMP 5- to 6-fold and increases the Hill coefficient. Different concentrations of cyclic AMP are required to dissociate the skeletal and heart muscle enzymes. The presence of MgATP increases the concentration of cyclic AMP required to dissociate the skeletal muscle enzyme but decreases the concentration necessary to dissociate the heart enzyme.", "contents": "Comparison of adenosine 3':5'-monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle. Homogeneous preparations of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase from rabbit skeletal (Peak I) and bovine heart muscle have been compared. Each enzyme has an S20,w value of 7.0. Each enzyme binds 2 mol of cyclic AMP per mol of enzyme and is dissociated in the presence of saturating concentrations of cyclic AMP into a demeric regulatory subunit-cyclic AMP complex and two catalytic subunits. The isolated subunits recombine, resulting in the formation of the original holoenzyme in each case. Several differences between the two enzymes were found. Different salt concentrations are necessary for elution of the respective enzyme from DEAE-cellulose. Their regulatory subunits differ with respect to their sedimentation constants and mobility on sodium dodecyl sulfate gel electrophoresis. The regulatory subunit of the heart enzyme is rapidly phosphorylated by MgATP but this does not occur with the skeletal muscle enzyme. MgATP is bound with high affinity only to the skeletal muscle enzyme. The enzymes have different apparent dissociation constants and Hill coefficients for cyclic AMP binding. With the skeletal muscle enzyme MgATP increases the dissociation constants for cyclic AMP about 10-fold and decreases the Hill coefficient, while with the heart enzyme phosphorylation decreases the cissociation constant for cyclic AMP 5- to 6-fold and increases the Hill coefficient. Different concentrations of cyclic AMP are required to dissociate the skeletal and heart muscle enzymes. The presence of MgATP increases the concentration of cyclic AMP required to dissociate the skeletal muscle enzyme but decreases the concentration necessary to dissociate the heart enzyme."} {"id": "PMID:170271", "title": "Insulin-sensitive phosphodiesterase. Its localization, hormonal stimulation, and oxidative stabilization.", "content": "As it was shown previoulsy by others, the membrane-bound phosphodiesterase (cyclic adenosine 3':5'-monophosphate phosphodiesterase) of rat epididymal fat cells was stimulated when intact cells were exposed to insulin. The levels of stimulation observed in the present study in the cell homogenate and microsomal fraction were approximately 2.0- to 2.5-fold and 2.5- to 3.0-fold, respectively, when the initial substrate level was 100 nM and insulin concentration was 1 to 3 nM. When the microsomal fraction was subjected to a sucrose density gradient centrifugation, most of the insulin-sensitive phosphodiesterase activity was fractionated into the \"light\" microsomal fraction which was rich in NADH2:potassium ferricyanide:oxidoreductase) and low in 5'-AMPase, adenylate cyclase, and insulin-binding activities. The latter three activities were mostly fractionated into the \"heavy\" microsomal fraction. Both basal and insulin-stimulated phosphodiesterase activities were low when cells were homogenized in the presence of N-ethylmaleimide or p-chloromercuribenzoate. The insulin-stimulated enzyme activity was also low when cells were homogenized in the presence of --SH compounds (e.g. dithiothreitol) or certain metal-chelating agents (e.g. ethylene glycol bis(beta-aminoethyl ehter)-N,N'-tetraacetate (EGTA)), or in a nitrogen atmosphere. The effect of EGTA was prevented by the addition of certain heavy metal ions but not by the addition of Ca2+ or Ca2+ plus Mg2+ ions. When cells were homogenized in the presence of certain oxidants (e.g. diamide, sodium tetrathionate, or air), a high plus-insulin activity was observed; this activity was not lowered by subsequent treatment of the enzyme with N-ethylmaleimede, EGTA, or fresh cell homogenate that was prepared in the presence of EGTA. However, the activity of an apparently oxidized enzyme could still be lowered by treatment woth dithiothreitol. A partially purified enzyme in the enzyme in the microsomal fraction was fairly stable both in basal and insulin-stimulated states (fully active after 35 days when kept at -20degrees). EGTA added to the homogenization buffer lowered the basal phosphodiesterase activity, but this effect was reversed by the addition of Ca2+ ions. EGTA also decreased the enzyme activity that was stimulated by norepinephrine. However, neither EGTA nor dithiothreitol had any effect on the activities of 5'-AMPase, NADH-dehydrogenase, and malate dehydrogenase of fat cells. The above data indicate that most of the insulin-sensitive phosphodiesterase and the so-called \"cell membrane markers\" are associated with different subcellular particles in the cell homogenate. In addition, the data seem to indicate that the insulin-stimulated phosphodiesterase has certain --SH groups and that the activity of the enzyme is stabilized when the --SH groups are oxidized by certain oxidants including molecular oxygen. It is suggested that the air oxidation of the enzyme is catalyzed by a trace of certain heavy metal ions and, therefore, can be blocked by a metal-chelating agent.", "contents": "Insulin-sensitive phosphodiesterase. Its localization, hormonal stimulation, and oxidative stabilization. As it was shown previoulsy by others, the membrane-bound phosphodiesterase (cyclic adenosine 3':5'-monophosphate phosphodiesterase) of rat epididymal fat cells was stimulated when intact cells were exposed to insulin. The levels of stimulation observed in the present study in the cell homogenate and microsomal fraction were approximately 2.0- to 2.5-fold and 2.5- to 3.0-fold, respectively, when the initial substrate level was 100 nM and insulin concentration was 1 to 3 nM. When the microsomal fraction was subjected to a sucrose density gradient centrifugation, most of the insulin-sensitive phosphodiesterase activity was fractionated into the \"light\" microsomal fraction which was rich in NADH2:potassium ferricyanide:oxidoreductase) and low in 5'-AMPase, adenylate cyclase, and insulin-binding activities. The latter three activities were mostly fractionated into the \"heavy\" microsomal fraction. Both basal and insulin-stimulated phosphodiesterase activities were low when cells were homogenized in the presence of N-ethylmaleimide or p-chloromercuribenzoate. The insulin-stimulated enzyme activity was also low when cells were homogenized in the presence of --SH compounds (e.g. dithiothreitol) or certain metal-chelating agents (e.g. ethylene glycol bis(beta-aminoethyl ehter)-N,N'-tetraacetate (EGTA)), or in a nitrogen atmosphere. The effect of EGTA was prevented by the addition of certain heavy metal ions but not by the addition of Ca2+ or Ca2+ plus Mg2+ ions. When cells were homogenized in the presence of certain oxidants (e.g. diamide, sodium tetrathionate, or air), a high plus-insulin activity was observed; this activity was not lowered by subsequent treatment of the enzyme with N-ethylmaleimede, EGTA, or fresh cell homogenate that was prepared in the presence of EGTA. However, the activity of an apparently oxidized enzyme could still be lowered by treatment woth dithiothreitol. A partially purified enzyme in the enzyme in the microsomal fraction was fairly stable both in basal and insulin-stimulated states (fully active after 35 days when kept at -20degrees). EGTA added to the homogenization buffer lowered the basal phosphodiesterase activity, but this effect was reversed by the addition of Ca2+ ions. EGTA also decreased the enzyme activity that was stimulated by norepinephrine. However, neither EGTA nor dithiothreitol had any effect on the activities of 5'-AMPase, NADH-dehydrogenase, and malate dehydrogenase of fat cells. The above data indicate that most of the insulin-sensitive phosphodiesterase and the so-called \"cell membrane markers\" are associated with different subcellular particles in the cell homogenate. In addition, the data seem to indicate that the insulin-stimulated phosphodiesterase has certain --SH groups and that the activity of the enzyme is stabilized when the --SH groups are oxidized by certain oxidants including molecular oxygen. It is suggested that the air oxidation of the enzyme is catalyzed by a trace of certain heavy metal ions and, therefore, can be blocked by a metal-chelating agent."} {"id": "PMID:170272", "title": "High and low reduction potential 4Fe-4S clusters in Azotobacter vinelandii (4Fe-4S) 2ferredoxin I. Influence of the polypeptide on the reduction potentials.", "content": "Azotobacter vinelandii (4Fe-4S)2 ferredoxin I (Fd I) is an electron transfer protein with Mr equals 14,500 and Eo equals -420 mv. It exhibits and EPR signal of g equals 2.01 in its isolated form. This resonance is almost identical with the signal that originates from a \"super-oxidized\" state of the 4Fe-4S cluster of potassium ferricyanide-treated Clostridium ferredoxin. A cluster that exhibits this EPR signal at g equals 2.01 is in the same formal oxidation state as the cluster in oxidized Chromatium High-Potential-Iron-Protein (HiPIP). On photoreduction of Fd I with spinach chloroplast fragments, the resonance at g equals 2.01 vanishes and no EPR signal is observed. This EPR behavior is analogous to that of reduced HiPIP, which also fails to exhibit an EPR spectrum. These characteristics suggest that a cluster in A. vinelandii Fd I functions between the same pair of states on reduction as does the cluster in HiPIP, but with a midpoint reduction potential of -420 mv in contrast to the value of +350 mv characteristic of HiPIP. Quantitative EPR and stoichoimetry studies showed that only one 4Fe-4S cluster in this (4Fe-4S)2 ferredoxin is reduced. Oxidation of Fd I with potassium ferricyanide results in the uptake of 1 electron/mol as determined by quantitative EPR spectroscopy. This indicates that a cluster in Fd I shows no electron paramagnetic resonance in the isolated form of the protein accepts an electron on oxidation, as indicated by the EPR spectrum, and becomes paramagnetic. The EPR behavior of this oxidizable cluster indicates that it also functions between the same pair of oxidation states as does the Fe-S cluster in HiPIP. The midpoint reduction potential of this cluster is approximately +340 mv. A. vinelandii Fd I is the first example of an iron-sulfur protein which contains both a high potential cluster (approximately +340 mv) and a low potential cluster (-420 mv). Both Fe-S clusters appear to function between the same pair of oxidation states as the single Fe-S cluster in Chromatium HiPIP, although the midpoint reduction potentials of the two clusters are approximately 760 mv different.", "contents": "High and low reduction potential 4Fe-4S clusters in Azotobacter vinelandii (4Fe-4S) 2ferredoxin I. Influence of the polypeptide on the reduction potentials. Azotobacter vinelandii (4Fe-4S)2 ferredoxin I (Fd I) is an electron transfer protein with Mr equals 14,500 and Eo equals -420 mv. It exhibits and EPR signal of g equals 2.01 in its isolated form. This resonance is almost identical with the signal that originates from a \"super-oxidized\" state of the 4Fe-4S cluster of potassium ferricyanide-treated Clostridium ferredoxin. A cluster that exhibits this EPR signal at g equals 2.01 is in the same formal oxidation state as the cluster in oxidized Chromatium High-Potential-Iron-Protein (HiPIP). On photoreduction of Fd I with spinach chloroplast fragments, the resonance at g equals 2.01 vanishes and no EPR signal is observed. This EPR behavior is analogous to that of reduced HiPIP, which also fails to exhibit an EPR spectrum. These characteristics suggest that a cluster in A. vinelandii Fd I functions between the same pair of states on reduction as does the cluster in HiPIP, but with a midpoint reduction potential of -420 mv in contrast to the value of +350 mv characteristic of HiPIP. Quantitative EPR and stoichoimetry studies showed that only one 4Fe-4S cluster in this (4Fe-4S)2 ferredoxin is reduced. Oxidation of Fd I with potassium ferricyanide results in the uptake of 1 electron/mol as determined by quantitative EPR spectroscopy. This indicates that a cluster in Fd I shows no electron paramagnetic resonance in the isolated form of the protein accepts an electron on oxidation, as indicated by the EPR spectrum, and becomes paramagnetic. The EPR behavior of this oxidizable cluster indicates that it also functions between the same pair of oxidation states as does the Fe-S cluster in HiPIP. The midpoint reduction potential of this cluster is approximately +340 mv. A. vinelandii Fd I is the first example of an iron-sulfur protein which contains both a high potential cluster (approximately +340 mv) and a low potential cluster (-420 mv). Both Fe-S clusters appear to function between the same pair of oxidation states as the single Fe-S cluster in Chromatium HiPIP, although the midpoint reduction potentials of the two clusters are approximately 760 mv different."} {"id": "PMID:170273", "title": "Inhibition of proteolytic degradation of low density lipoprotein in human fibroblasts by chloroquine, concanavalin A, and Triton WR 1339.", "content": "The proteolytic degradation of 125I-labeled low density lipoprotein by monolayers of cultured human fibroblasts was prevented by exposure of the cells to chloroquine, an agent that has been reported previously to inhibit lysosomal degradative processes. Chloroquine did not inhibit the binding of low density lipoprotein to its cell surface receptor. However, the two regulatory actions that normally follow low density lipoprotein binding to its receptor, namely suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and stimulation of cholesteryl ester formation, were both prevented when degradation of the lipoprotein was inhibited by chloroquine. Two other agents affecting lysosomal function, Triton WR 1339 and concanavalin A, also inhibited the proteolytic degradation of low density lipoprotein in intact fibroblasts and simultaneously prevented low density lipoprotein-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and stimulation of cholesteryl ester formation. Unlike chloroquine, however, these two agents also affect the binding of low density lipoprotein to the cells. The inhibitory action of chloropuine, concanavalin A, and Triton WR 1339 could each be reversed by removal of the agent from the culture medium. These in vivo culture data, together with the observation that cell-free extracts of fibroblasts maximally degrade 125I-labeled low density lipoprotein at pH 4 and do not form acid-soluble material above pH 6, are consistent with the hypothesis that the proteolytic degradation of low density lipoprotein by monolayers of fibroblasts occurs within lysosomes. The data also suggest that normal lysosomal function is required in order for low density lipoprotein to regulate cholesterol synthesis and cholesteryl ester formation in the fibroblast system.", "contents": "Inhibition of proteolytic degradation of low density lipoprotein in human fibroblasts by chloroquine, concanavalin A, and Triton WR 1339. The proteolytic degradation of 125I-labeled low density lipoprotein by monolayers of cultured human fibroblasts was prevented by exposure of the cells to chloroquine, an agent that has been reported previously to inhibit lysosomal degradative processes. Chloroquine did not inhibit the binding of low density lipoprotein to its cell surface receptor. However, the two regulatory actions that normally follow low density lipoprotein binding to its receptor, namely suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and stimulation of cholesteryl ester formation, were both prevented when degradation of the lipoprotein was inhibited by chloroquine. Two other agents affecting lysosomal function, Triton WR 1339 and concanavalin A, also inhibited the proteolytic degradation of low density lipoprotein in intact fibroblasts and simultaneously prevented low density lipoprotein-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and stimulation of cholesteryl ester formation. Unlike chloroquine, however, these two agents also affect the binding of low density lipoprotein to the cells. The inhibitory action of chloropuine, concanavalin A, and Triton WR 1339 could each be reversed by removal of the agent from the culture medium. These in vivo culture data, together with the observation that cell-free extracts of fibroblasts maximally degrade 125I-labeled low density lipoprotein at pH 4 and do not form acid-soluble material above pH 6, are consistent with the hypothesis that the proteolytic degradation of low density lipoprotein by monolayers of fibroblasts occurs within lysosomes. The data also suggest that normal lysosomal function is required in order for low density lipoprotein to regulate cholesterol synthesis and cholesteryl ester formation in the fibroblast system."} {"id": "PMID:170274", "title": "Solubilization of the [8-lysine]vasopressin receptor and adenylate cyclase from pig kidney plasma membranes.", "content": "Adenylate cyclase and the [8-lysine]vasopressin receptor were solubilized from pig kidney medulla membranes using the nonionic detergent Triton X-100. Optimal conditions for solubilization were under continuous stirring in a medium containing 0.5% (/v) Triton X-100, 100 mM Tris-HCl, pH 8, and 10 mM MgCl2. Both adenylate cyclase activity and [3H][8-lysine]vasopressin binding activity were recovered in a -26,000 X g supernatant of detergent-treated membranes. The yield of solubilized adenylate cyclase was nearly 100%. The soluble enzyme was no longer sensitive to antidiuretic hormone but was slightly activated by sodium fluoride. The affinity of the soluble receptor for [8-lysine]vasopresin was les than that of the membrane-bound receptor (mean apparent Km values, respectively 10(-7) M and 2 X 10(-8) M), however binding cooperativity was preserved. Hill coefficients were 1.42 for the soluble receptor and 1.50 for the membrane receptor. The soluble receptor discriminated as efficiently as did the membrane receptor between [8-lysine-a1vasopressin and oxytocin. The yield of spolubilized receptor was only 30% despite the fact that all binding activity had disappeared from the residual pellet of detergent-treated membranes. When the membranous receptors were occupied before solubilization and the latter was performed under conditions in which dissociation of the hormone-receptor comples is slow, i.e. at low temperature, 65% to 100% of the hormone-receptor complex was recovered in the soluble fraction. The soluble hormone-receptor complex partially dissociated on rewarming whereas the free hormone concentration was kept unchanged in the medium. The residual binding capacity, which was 30% of the initial value, was identical with that determined when the receptor was solubilized in free form before incubation with labeled hormone. It was concluded that (a) solubilization of the receptor molecules was complete, (b) during solubilization two forms of the receptor appear, of which only one is accessible to the hormone, (c) occupancy of the receptor by the hormone prevented the formation of the nonaccessible form, and (d) some component or components of the soluble fraction might be responsible for the loss in apparent affinity.", "contents": "Solubilization of the [8-lysine]vasopressin receptor and adenylate cyclase from pig kidney plasma membranes. Adenylate cyclase and the [8-lysine]vasopressin receptor were solubilized from pig kidney medulla membranes using the nonionic detergent Triton X-100. Optimal conditions for solubilization were under continuous stirring in a medium containing 0.5% (/v) Triton X-100, 100 mM Tris-HCl, pH 8, and 10 mM MgCl2. Both adenylate cyclase activity and [3H][8-lysine]vasopressin binding activity were recovered in a -26,000 X g supernatant of detergent-treated membranes. The yield of solubilized adenylate cyclase was nearly 100%. The soluble enzyme was no longer sensitive to antidiuretic hormone but was slightly activated by sodium fluoride. The affinity of the soluble receptor for [8-lysine]vasopresin was les than that of the membrane-bound receptor (mean apparent Km values, respectively 10(-7) M and 2 X 10(-8) M), however binding cooperativity was preserved. Hill coefficients were 1.42 for the soluble receptor and 1.50 for the membrane receptor. The soluble receptor discriminated as efficiently as did the membrane receptor between [8-lysine-a1vasopressin and oxytocin. The yield of spolubilized receptor was only 30% despite the fact that all binding activity had disappeared from the residual pellet of detergent-treated membranes. When the membranous receptors were occupied before solubilization and the latter was performed under conditions in which dissociation of the hormone-receptor comples is slow, i.e. at low temperature, 65% to 100% of the hormone-receptor complex was recovered in the soluble fraction. The soluble hormone-receptor complex partially dissociated on rewarming whereas the free hormone concentration was kept unchanged in the medium. The residual binding capacity, which was 30% of the initial value, was identical with that determined when the receptor was solubilized in free form before incubation with labeled hormone. It was concluded that (a) solubilization of the receptor molecules was complete, (b) during solubilization two forms of the receptor appear, of which only one is accessible to the hormone, (c) occupancy of the receptor by the hormone prevented the formation of the nonaccessible form, and (d) some component or components of the soluble fraction might be responsible for the loss in apparent affinity."} {"id": "PMID:170275", "title": "Human liver aldehyde dehydrogenase. Esterase activity.", "content": "Human liver aldehyde dehydrogenase has been found to be capable of hydrolyzing p-nitrophenyl esters. Esterase and dehydrogenase activities exhibited identical ion exchange and affinity properties, indicating that the same protein catalyzes both reactions. Competitive inhibition of esterase activity by glyceraldehyde and chloral hydrate furnished evidence that p-nitrophenyl acetate was hydrolyzed at the aldehyde binding site for dehydrogenase activity. Pyridine nucleotides modified esterase activity; NAD+ accelerated the rate of p-nitrophenyl acetate hydrolysis more that 5-fold, whereas NADH increased activity by a factor of 2. Activation constants of 117 muM for NAD+ and 3.5 muM for NADH were obtained from double reciprocal plots of initial rates as a function of modifier concentration at pH 7. The kinetics of activation of ester hydrolysis were consistent with random addition of pyridine nucleotide modifier and ester substrate to this enzyme.", "contents": "Human liver aldehyde dehydrogenase. Esterase activity. Human liver aldehyde dehydrogenase has been found to be capable of hydrolyzing p-nitrophenyl esters. Esterase and dehydrogenase activities exhibited identical ion exchange and affinity properties, indicating that the same protein catalyzes both reactions. Competitive inhibition of esterase activity by glyceraldehyde and chloral hydrate furnished evidence that p-nitrophenyl acetate was hydrolyzed at the aldehyde binding site for dehydrogenase activity. Pyridine nucleotides modified esterase activity; NAD+ accelerated the rate of p-nitrophenyl acetate hydrolysis more that 5-fold, whereas NADH increased activity by a factor of 2. Activation constants of 117 muM for NAD+ and 3.5 muM for NADH were obtained from double reciprocal plots of initial rates as a function of modifier concentration at pH 7. The kinetics of activation of ester hydrolysis were consistent with random addition of pyridine nucleotide modifier and ester substrate to this enzyme."} {"id": "PMID:170276", "title": "Human liver akdehyde dehydrogenase. Kinetics of aldehyde oxidation.", "content": "Steady state initial velocity studies were carried out to determine the kinetic mechanism of human liver aldehyde dehydrogenase. Intersecting double reciprocal plots obtained in the absence of inhibitors demonstrated that the dehydrogenase reaction proceeded by sequential addition of both substrates prior to release of products. Dead end inhibition patterns obtained with coenzyme and substrate analogues (e.g. thionicotinamide-AD+ and chloral hydrate) indicated that NAD+ and aldehyde can bind in random fashion. The patterns of inhibition by the product NADH and of substrate inhibition by glyceraldehyde were also consistent with this mechanism. However, comparisons between kinetic constants associated with the dehydrogenase and esterase activities of this enzyme suggested that most of the dehydrogenase reaction flux proceeds via formation of an initial binary NAD+-enzyme complex over a wide range of substrate and coenzyme concentrations.", "contents": "Human liver akdehyde dehydrogenase. Kinetics of aldehyde oxidation. Steady state initial velocity studies were carried out to determine the kinetic mechanism of human liver aldehyde dehydrogenase. Intersecting double reciprocal plots obtained in the absence of inhibitors demonstrated that the dehydrogenase reaction proceeded by sequential addition of both substrates prior to release of products. Dead end inhibition patterns obtained with coenzyme and substrate analogues (e.g. thionicotinamide-AD+ and chloral hydrate) indicated that NAD+ and aldehyde can bind in random fashion. The patterns of inhibition by the product NADH and of substrate inhibition by glyceraldehyde were also consistent with this mechanism. However, comparisons between kinetic constants associated with the dehydrogenase and esterase activities of this enzyme suggested that most of the dehydrogenase reaction flux proceeds via formation of an initial binary NAD+-enzyme complex over a wide range of substrate and coenzyme concentrations."} {"id": "PMID:170277", "title": "Structure of human high density lipoprotein reassembled in vitro. Radioimmunoassay studies.", "content": "Immunologic approaches to studying lipoprotein structure have been limited because the methods have not been quantitative enough. Recently we reported (Schonfeld, G., and Pfleger, B. (1974) J. Clin. Invest. 54, 236-246) a radioimmunoassay for human apoprotein A-1 (ApoA-I). Only 8% of the ApoA-I of high density lipoprotein (HDL) reacted in the radioimmunoassay system consisting of rabbit anti-human ApoA-I, 125I-ApoA-I, and unlabeled ApoA-I. We suggested that the ApoA-I in HDL were poorly reactive in the radioimmunoassay because they were \"masked\" by lipid- or protein-protein interactions. To test this, \"lipoproteins\" were reconstituted from lipids and apoproteins and assayed for their reactivity in the radioimmunoassay. Apo-HDL, ApoA-I alone, or ApoA-I + ApoA-II were sonified with lecithin or with lipids extracted from HDL. Sonicates were fractionated by ultracentrifugation or by Sepharose 4B chromatography. HDLs were also made by incubating dispersed lecithin or lecithin + cholesterol with Apo-HDL, ApoA-I, or ApoA-II. The lipoproteins were analyzed for lipids and protein chemically. Apoprotein compositions were determined by polyacrylamide disc gel electrophoresis. ApoA-I content by radioimmunoassay then was compared with the ApoA-I content obtained by disc gel electrophoresis. Most reconstituted \"lipoproteins\" had less than the expected ApoA-I contents. Discrepancies between ApoA-I contents were greatest for lipoproteins prepared from Apo-HDL and HDL-lipids (20 to 30% of expected contents). Discrepancies were smaller for particles prepared with lecithin, with ApoA-I alone or with ApoA-I + ApoA-II (40 to 85% of expected). HDLs made by incubation were less reactive than those prepared by sonication. Thus, the reactivity of ApoA-I in the radioimmunoassay could be diminished by causing it to interact with lipids or their apoproteins, or both, suggesting that antigenic sites became masked. From this one can extrapolate that the poor reactivity of the ApoA-I in HDL isolated from plasma also may have been due to the masking of some of its antigenic determinants. The identification of the determinants involved awaits the development of radioimmunoassays for specific regions of ApoA-I.", "contents": "Structure of human high density lipoprotein reassembled in vitro. Radioimmunoassay studies. Immunologic approaches to studying lipoprotein structure have been limited because the methods have not been quantitative enough. Recently we reported (Schonfeld, G., and Pfleger, B. (1974) J. Clin. Invest. 54, 236-246) a radioimmunoassay for human apoprotein A-1 (ApoA-I). Only 8% of the ApoA-I of high density lipoprotein (HDL) reacted in the radioimmunoassay system consisting of rabbit anti-human ApoA-I, 125I-ApoA-I, and unlabeled ApoA-I. We suggested that the ApoA-I in HDL were poorly reactive in the radioimmunoassay because they were \"masked\" by lipid- or protein-protein interactions. To test this, \"lipoproteins\" were reconstituted from lipids and apoproteins and assayed for their reactivity in the radioimmunoassay. Apo-HDL, ApoA-I alone, or ApoA-I + ApoA-II were sonified with lecithin or with lipids extracted from HDL. Sonicates were fractionated by ultracentrifugation or by Sepharose 4B chromatography. HDLs were also made by incubating dispersed lecithin or lecithin + cholesterol with Apo-HDL, ApoA-I, or ApoA-II. The lipoproteins were analyzed for lipids and protein chemically. Apoprotein compositions were determined by polyacrylamide disc gel electrophoresis. ApoA-I content by radioimmunoassay then was compared with the ApoA-I content obtained by disc gel electrophoresis. Most reconstituted \"lipoproteins\" had less than the expected ApoA-I contents. Discrepancies between ApoA-I contents were greatest for lipoproteins prepared from Apo-HDL and HDL-lipids (20 to 30% of expected contents). Discrepancies were smaller for particles prepared with lecithin, with ApoA-I alone or with ApoA-I + ApoA-II (40 to 85% of expected). HDLs made by incubation were less reactive than those prepared by sonication. Thus, the reactivity of ApoA-I in the radioimmunoassay could be diminished by causing it to interact with lipids or their apoproteins, or both, suggesting that antigenic sites became masked. From this one can extrapolate that the poor reactivity of the ApoA-I in HDL isolated from plasma also may have been due to the masking of some of its antigenic determinants. The identification of the determinants involved awaits the development of radioimmunoassays for specific regions of ApoA-I."} {"id": "PMID:170278", "title": "The sequence of a peptide containing the active site phosphohistidine residue of phosphoglycerate mutase from chicken breast muscle.", "content": "Phosphoglycerate mutase is phosphorylated on a histidine residue by the cofactor of the reaction, 2,3-bisphosphoglycerate (Rose, Z. B. (1970) Arch. Biochem. Biophys. 140, 508-513). The phosphoryl group is readily transferred to the normal acceptors, 3-phosphoglycerate and 2-phosphoglycerate, or to water in the presence of glycolate-2-P. An acid-labile phosphorylated decapeptide has been purified from a tryptic digest of the phosphoenzyme. The amino acid sequence of the peptide has been determined to be: Aal-Gly-Gln-Leu-Asp-Glu-Ser-His-Arg. This sequence bears a striking analogy to part of a highly conserved region of lactate dehydrogenase (residues 100 to 109) (Taylor, S. S., Oxley, S. S., Allison, W. S., and Kaplan, N. O. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 1970-1974). Evidence from x-ray crystallographic studies indicates that the two enzymes are similar in tertiary structure (Campbell, J. W., Watson, H. C. and Hodgson, G. I. (1974) Nature 250, 301-303).", "contents": "The sequence of a peptide containing the active site phosphohistidine residue of phosphoglycerate mutase from chicken breast muscle. Phosphoglycerate mutase is phosphorylated on a histidine residue by the cofactor of the reaction, 2,3-bisphosphoglycerate (Rose, Z. B. (1970) Arch. Biochem. Biophys. 140, 508-513). The phosphoryl group is readily transferred to the normal acceptors, 3-phosphoglycerate and 2-phosphoglycerate, or to water in the presence of glycolate-2-P. An acid-labile phosphorylated decapeptide has been purified from a tryptic digest of the phosphoenzyme. The amino acid sequence of the peptide has been determined to be: Aal-Gly-Gln-Leu-Asp-Glu-Ser-His-Arg. This sequence bears a striking analogy to part of a highly conserved region of lactate dehydrogenase (residues 100 to 109) (Taylor, S. S., Oxley, S. S., Allison, W. S., and Kaplan, N. O. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 1970-1974). Evidence from x-ray crystallographic studies indicates that the two enzymes are similar in tertiary structure (Campbell, J. W., Watson, H. C. and Hodgson, G. I. (1974) Nature 250, 301-303)."} {"id": "PMID:170279", "title": "The self-association of the apo-Gln-I and apo-Gln-II polypeptides of human high density serum lipoproteins.", "content": "The major polypeptide components of human high density lipoprotein, apo-Gln-I and apo-Gln-II, self-associate at pH 8.3 and ionic strength 0.045. The dimeric (MW = 56,800) association constant for apo-Gln-I is 1.3 X 10(4)liters/mol. apo-Gln-II is tetrameric at all experimentally accessible concentrations. Self-association of apo-Gln-I is accompanied by minor conformational alterations distinct from that induced by saturating levels of bound amphiphilic ligands. These results are discussed with respect to the design of reconstitution experiments between the apoproteins and lipids.", "contents": "The self-association of the apo-Gln-I and apo-Gln-II polypeptides of human high density serum lipoproteins. The major polypeptide components of human high density lipoprotein, apo-Gln-I and apo-Gln-II, self-associate at pH 8.3 and ionic strength 0.045. The dimeric (MW = 56,800) association constant for apo-Gln-I is 1.3 X 10(4)liters/mol. apo-Gln-II is tetrameric at all experimentally accessible concentrations. Self-association of apo-Gln-I is accompanied by minor conformational alterations distinct from that induced by saturating levels of bound amphiphilic ligands. These results are discussed with respect to the design of reconstitution experiments between the apoproteins and lipids."} {"id": "PMID:170280", "title": "Heterogneeous 5'-terminal structures occur on vesicular stomatitis virus mRNAs.", "content": "Four alternative structures occur at the 5' ends of vesicular stomatitis virus mRNAs synthesized in infected cells and are separated conveniently by a technique described here. Sixty-five to seventy per cent of the mRNA molecules have the 5' end structure m7G5'ppp5'(m)AmpAp and about 20% have a more highly modified structure m7G5'ppp5'(m)AmpmAmpCp. The base of the first adenosine in each sequence is methylated in about one-half of the ends of each type and kinetic experiments suggest that the latter sequence is derived from the former by further methylations. The remaining 10 to 15% of the 5' ends are pppAp and pppGp in approximately equimolar yields. This heterogeneity with respect to 5' end structure is found within each of the vesicular stomatitis virus mRNA species examined. The mRNA molecules with 5'-triphosphate ends accumulate throughout the infection but are not found on ribosomes, suggesting that they lack a structure(s) required for ribosome recognition. In contrast to mRNA, virion RNA has a single 5' end structure, pppAp.", "contents": "Heterogneeous 5'-terminal structures occur on vesicular stomatitis virus mRNAs. Four alternative structures occur at the 5' ends of vesicular stomatitis virus mRNAs synthesized in infected cells and are separated conveniently by a technique described here. Sixty-five to seventy per cent of the mRNA molecules have the 5' end structure m7G5'ppp5'(m)AmpAp and about 20% have a more highly modified structure m7G5'ppp5'(m)AmpmAmpCp. The base of the first adenosine in each sequence is methylated in about one-half of the ends of each type and kinetic experiments suggest that the latter sequence is derived from the former by further methylations. The remaining 10 to 15% of the 5' ends are pppAp and pppGp in approximately equimolar yields. This heterogeneity with respect to 5' end structure is found within each of the vesicular stomatitis virus mRNA species examined. The mRNA molecules with 5'-triphosphate ends accumulate throughout the infection but are not found on ribosomes, suggesting that they lack a structure(s) required for ribosome recognition. In contrast to mRNA, virion RNA has a single 5' end structure, pppAp."} {"id": "PMID:170281", "title": "Affinity labeling of the inhibitory DPNH site of bovine liver glutamate dehydrogenase by 5'-fluorosulfonylbenzoyl adenosine.", "content": "A new adenosine analogue has been synthesized, 5'-fluorosulfonylbenzoyl adenosine, which reacts covalently with bovine liver glutamate dehydrogenase with the incorporation of approximately 1 mol of 5'-sulfonylbenzoyl adenosine per peptide chain. Native glutamate dehydrogenase is known to be inhibited by relatively high concentrations of DPNH by binding to a second noncatalytic site; the major change in the kinetic characteristics of the modified enzyme is a total loss of this inhibition by DPNH. The modified enzyme retains full catalytic activity as measured in the absence of allosteric ligands, is still inhibited more than 90% by GTP, and is activated normally by ADP. These results demonstrate that the catalytic as well as the GTP and ADP regulatory sites are distinct from the inhibitory DPNH site. The rate constant for reaction of 5'-fluorosulfonylbenzoyl adenosine is decreased by high concentrations of DPNH alone or by DPNH plus GTP, but not by the substrate alpha-ketoglutarate, the coenzymes DPN or TPNH, or the regulators ADP or GTP alone. These observations are consistent with the postulate that the 5'-fluorosulfonylbenzoyl adenosine attacks exclusively the second inhibitory DPNH site. The DPNH inhibition is abolished when an average of only 0.5 mol of 5'-sulfonylbenzoyl adenosine per peptide chain has been incorporated. The structure of 5'-fluorosulfonylbenzoyl adenosine is critical in determining the course of the modification reaction. The smaller compound p-fluorosulfonylbenzoic acid does not affect the kinetic characteristics of the enzyme, and the isomeric compound 3'-fluorosulfonylbenzoyl adenosine produces a different pattern of changes in the regulatory properties (Pal. P. K., Wechter, W. J., and Colman, R. F. (1975) Biochemistry 14, 707-715). Indeed, enzyme which has combined stoichiometrically with 5'-fluorosulfonylbenzoyl adenosine is still able to react with 3'-fluorosulfonylbenzoyl adenosine; thus, the two adenosine analogues appear to react at distinct sites on glutamate dehydrogenase. It is proposed that 5'-fluorosulfonylbenzoyl adenosine will be complementary to 3'-fluorosulfonylbenzoyl adenosine as a general affinity label for dehydrogenases as well as other classes of enzymes which use adenine nucleotides as substrates or regulators.", "contents": "Affinity labeling of the inhibitory DPNH site of bovine liver glutamate dehydrogenase by 5'-fluorosulfonylbenzoyl adenosine. A new adenosine analogue has been synthesized, 5'-fluorosulfonylbenzoyl adenosine, which reacts covalently with bovine liver glutamate dehydrogenase with the incorporation of approximately 1 mol of 5'-sulfonylbenzoyl adenosine per peptide chain. Native glutamate dehydrogenase is known to be inhibited by relatively high concentrations of DPNH by binding to a second noncatalytic site; the major change in the kinetic characteristics of the modified enzyme is a total loss of this inhibition by DPNH. The modified enzyme retains full catalytic activity as measured in the absence of allosteric ligands, is still inhibited more than 90% by GTP, and is activated normally by ADP. These results demonstrate that the catalytic as well as the GTP and ADP regulatory sites are distinct from the inhibitory DPNH site. The rate constant for reaction of 5'-fluorosulfonylbenzoyl adenosine is decreased by high concentrations of DPNH alone or by DPNH plus GTP, but not by the substrate alpha-ketoglutarate, the coenzymes DPN or TPNH, or the regulators ADP or GTP alone. These observations are consistent with the postulate that the 5'-fluorosulfonylbenzoyl adenosine attacks exclusively the second inhibitory DPNH site. The DPNH inhibition is abolished when an average of only 0.5 mol of 5'-sulfonylbenzoyl adenosine per peptide chain has been incorporated. The structure of 5'-fluorosulfonylbenzoyl adenosine is critical in determining the course of the modification reaction. The smaller compound p-fluorosulfonylbenzoic acid does not affect the kinetic characteristics of the enzyme, and the isomeric compound 3'-fluorosulfonylbenzoyl adenosine produces a different pattern of changes in the regulatory properties (Pal. P. K., Wechter, W. J., and Colman, R. F. (1975) Biochemistry 14, 707-715). Indeed, enzyme which has combined stoichiometrically with 5'-fluorosulfonylbenzoyl adenosine is still able to react with 3'-fluorosulfonylbenzoyl adenosine; thus, the two adenosine analogues appear to react at distinct sites on glutamate dehydrogenase. It is proposed that 5'-fluorosulfonylbenzoyl adenosine will be complementary to 3'-fluorosulfonylbenzoyl adenosine as a general affinity label for dehydrogenases as well as other classes of enzymes which use adenine nucleotides as substrates or regulators."} {"id": "PMID:170282", "title": "Selective effects of MgCl2 and temperature on the initiation of transcription at lac, gal, and lambda promoters.", "content": "We have studied the effect of Mg2+ on the formation of transcription preinitiation complexes (open complexes) at two adenosine 3':5'-monophosphate (cyclic AMP)-cyclic AMP receptor protein (CRP)-dependent promoters (lac and gal) and two phage lambda promoters, PL and PR. Mg2+ strongly interferes with open complex formation at the lac and gal promoters, partially inhibits the lambda PR promoter, and is without effect on the lambda PL promoter. Mutations in the lac and gal promoters can affect the response of the promoter to Mg2+. Cyclic AMP and CRP specifically reduce the inhibition of the lac and gal promoters by Mg2+. These factors also affect open complexes at lac and gal by (a) increasing the rate at which they are formed and (b) lowering the midpoint of the temperature transition curve for their formation by about 10 degrees. Open complexes at the lac promoter are more unstable to cooling, even in the presence of CRP and cyclic AMP, than open complexes at lambda promoters. Our studies suggest that the DNA of the lac and gal promoter regions is more resistant to denaturation than the DNA of phage promoter regions. Cyclic AMP and CRP act to decrease this stability, stimulating open complex formation under conditions unfavorable for DNA melting, e.g. low temperature and high Mg2+ concentrations.", "contents": "Selective effects of MgCl2 and temperature on the initiation of transcription at lac, gal, and lambda promoters. We have studied the effect of Mg2+ on the formation of transcription preinitiation complexes (open complexes) at two adenosine 3':5'-monophosphate (cyclic AMP)-cyclic AMP receptor protein (CRP)-dependent promoters (lac and gal) and two phage lambda promoters, PL and PR. Mg2+ strongly interferes with open complex formation at the lac and gal promoters, partially inhibits the lambda PR promoter, and is without effect on the lambda PL promoter. Mutations in the lac and gal promoters can affect the response of the promoter to Mg2+. Cyclic AMP and CRP specifically reduce the inhibition of the lac and gal promoters by Mg2+. These factors also affect open complexes at lac and gal by (a) increasing the rate at which they are formed and (b) lowering the midpoint of the temperature transition curve for their formation by about 10 degrees. Open complexes at the lac promoter are more unstable to cooling, even in the presence of CRP and cyclic AMP, than open complexes at lambda promoters. Our studies suggest that the DNA of the lac and gal promoter regions is more resistant to denaturation than the DNA of phage promoter regions. Cyclic AMP and CRP act to decrease this stability, stimulating open complex formation under conditions unfavorable for DNA melting, e.g. low temperature and high Mg2+ concentrations."} {"id": "PMID:170283", "title": "Cytoplasmic receptor protein for etiochalanolone in chick embryo liver.", "content": "Acute intermittent porphyria is a gentic disease associated with changes in the activity of some of the hepatic enzymes in the heme biosynthetic pathway and in the activity of delta4-5alpha-steroid reductase, an enzyme involved in steroid metabolism. Embryonic chick liver has been used as a model system to study the effects of several naturally occurring 5beta steroid metabolites on delta-aminolevulinic acid synthetase, the rate-limiting enzyme in the heme pathway (Granick, S., and Kappas, A. (1967) J. Biol. Chem. 242, 4587-4593). In this study we have identified in vitro a hepatic cytoplasmic receptor which binds [3H]-etiocholanolone (a 5beta-H androgen metabolite). The steroid-receptor complex has an apparent Kd value of 3.5 times 10(-6) M at 0-4degrees; the number of binding sites per cell is 23,000. The macromolecular complex sediments at approximately 4 S in a 5 to 20% sucrose gradient and is unaffected by KCl concentrations up to 0.4 M. The steroid-receptor complex can be destroyed by heat (60degrees) or proteolytic digestion and is inhibited by sulfhydryl-blocking agents. Competition studies revealed that among the nonradioactive steroids tested, all of the primary androgens and the progestins as well as their 5alpha and 5beta metabolites block the binding of [3H]etiochalanolone. Only the glucuronide derivative of etiocholanolone, glucocorticoids and their metabolites, 17beta-estradiol, and cyproterone compete poorly for the receptor. The steroid receptor described here appears to be different from the androgen receptor isolated from rat liver and prostate.", "contents": "Cytoplasmic receptor protein for etiochalanolone in chick embryo liver. Acute intermittent porphyria is a gentic disease associated with changes in the activity of some of the hepatic enzymes in the heme biosynthetic pathway and in the activity of delta4-5alpha-steroid reductase, an enzyme involved in steroid metabolism. Embryonic chick liver has been used as a model system to study the effects of several naturally occurring 5beta steroid metabolites on delta-aminolevulinic acid synthetase, the rate-limiting enzyme in the heme pathway (Granick, S., and Kappas, A. (1967) J. Biol. Chem. 242, 4587-4593). In this study we have identified in vitro a hepatic cytoplasmic receptor which binds [3H]-etiocholanolone (a 5beta-H androgen metabolite). The steroid-receptor complex has an apparent Kd value of 3.5 times 10(-6) M at 0-4degrees; the number of binding sites per cell is 23,000. The macromolecular complex sediments at approximately 4 S in a 5 to 20% sucrose gradient and is unaffected by KCl concentrations up to 0.4 M. The steroid-receptor complex can be destroyed by heat (60degrees) or proteolytic digestion and is inhibited by sulfhydryl-blocking agents. Competition studies revealed that among the nonradioactive steroids tested, all of the primary androgens and the progestins as well as their 5alpha and 5beta metabolites block the binding of [3H]etiochalanolone. Only the glucuronide derivative of etiocholanolone, glucocorticoids and their metabolites, 17beta-estradiol, and cyproterone compete poorly for the receptor. The steroid receptor described here appears to be different from the androgen receptor isolated from rat liver and prostate."} {"id": "PMID:170284", "title": "Assembly of the mitochondrial membrane system. Characterization of nuclear mutants of Saccharomyces cerevisiae with defects in mitochondrial ATPase and respiratory enzymes.", "content": "Mutants of Saccharomyces cereviaiae showing defects in cytochrome oxidase, coenzyme QH2-cytochrome c reductase, and rutamycin-sensitive ATPase are described. The mutations have been established to be nuclear, based on complementation with a cytoplasmic petite tester strain and 2:2 segregation of tetrads. Genetic analysis indicate the coenzyme QH2-cytochrome c reductase and cytochrome oxidase mutants fall into 9 and 10 different complementation groups, respectively. The mutants also form distinct classes based on absorption spectra of the mitochondrial cytochromes. Two of the ATPase mutants lack detectable F1 ATPase, while the third synthesizes F1 but does not integrate it into a membrane complex. The latter mutant is missing one of the mitochondrially synthesized subunits of the rutamycin-sensitive ATPase complex.", "contents": "Assembly of the mitochondrial membrane system. Characterization of nuclear mutants of Saccharomyces cerevisiae with defects in mitochondrial ATPase and respiratory enzymes. Mutants of Saccharomyces cereviaiae showing defects in cytochrome oxidase, coenzyme QH2-cytochrome c reductase, and rutamycin-sensitive ATPase are described. The mutations have been established to be nuclear, based on complementation with a cytoplasmic petite tester strain and 2:2 segregation of tetrads. Genetic analysis indicate the coenzyme QH2-cytochrome c reductase and cytochrome oxidase mutants fall into 9 and 10 different complementation groups, respectively. The mutants also form distinct classes based on absorption spectra of the mitochondrial cytochromes. Two of the ATPase mutants lack detectable F1 ATPase, while the third synthesizes F1 but does not integrate it into a membrane complex. The latter mutant is missing one of the mitochondrially synthesized subunits of the rutamycin-sensitive ATPase complex."} {"id": "PMID:170285", "title": "Evaluation of the physical properties of crown dental porcelain and the effect of newly developed anti-binding additive.", "content": "A colloidal silica-based substitute for the water added to dental porcelain has been developed which restricts rounding on firing and gives greater and indefinitely prolonged unfired biscuit strength. In conjunction with product evaluation, it has been found that both the modulus of rupture and the diametrical tensile strength of dental porcelains can be measured with a high degree of precision.", "contents": "Evaluation of the physical properties of crown dental porcelain and the effect of newly developed anti-binding additive. A colloidal silica-based substitute for the water added to dental porcelain has been developed which restricts rounding on firing and gives greater and indefinitely prolonged unfired biscuit strength. In conjunction with product evaluation, it has been found that both the modulus of rupture and the diametrical tensile strength of dental porcelains can be measured with a high degree of precision."} {"id": "PMID:170286", "title": "The surface area of aggregates applied to dental materials.", "content": "There is a continuing need for the complete characterization of the physical and chemical properties of dental materials. Among these properties is surface area. The problem is further complicated by the fact that most dental materials are, themselves, mixtures of two or more identifiable components. If the vapor adsorptive properties of these components are different in the mixture from that which would be expected of them collectively, then interaction is present. Interaction must not be confused with the lack of addivity which results from the limitations of the BET theory applied to mixtures. Equations are derived herein to estimate the extent of this latter source of variability and to correct for it giving a \"true\" surface area for the aggregate. Conversely, the adsorptive properties of either component can be calculated from the properties of the mixture and the remaining component together with the percentage composition. An immediate application can be made in determining the water-vapor adsorptive properties of human dentinal collagen without necessitating its removal from dentin. Any attempt to extract it chemically may produce denaturation or chain rupture thus precluding the possibility of direct determination. In the case of nitrogen adsorption, however, interaction definitely is indicated.", "contents": "The surface area of aggregates applied to dental materials. There is a continuing need for the complete characterization of the physical and chemical properties of dental materials. Among these properties is surface area. The problem is further complicated by the fact that most dental materials are, themselves, mixtures of two or more identifiable components. If the vapor adsorptive properties of these components are different in the mixture from that which would be expected of them collectively, then interaction is present. Interaction must not be confused with the lack of addivity which results from the limitations of the BET theory applied to mixtures. Equations are derived herein to estimate the extent of this latter source of variability and to correct for it giving a \"true\" surface area for the aggregate. Conversely, the adsorptive properties of either component can be calculated from the properties of the mixture and the remaining component together with the percentage composition. An immediate application can be made in determining the water-vapor adsorptive properties of human dentinal collagen without necessitating its removal from dentin. Any attempt to extract it chemically may produce denaturation or chain rupture thus precluding the possibility of direct determination. In the case of nitrogen adsorption, however, interaction definitely is indicated."} {"id": "PMID:170287", "title": "Surface and bulk characteristics of a polyether urethane for artificial hearts.", "content": "A segmented polyether urethane was used as the blood contacting surface in a series of 10 heart assist devices implanted in calves for periods up to 35 weeks. At termination, each was examined to correlate blood compatibility and device performance with surface properties, chemical purity, physical stability and affinity for lipid absorption.", "contents": "Surface and bulk characteristics of a polyether urethane for artificial hearts. A segmented polyether urethane was used as the blood contacting surface in a series of 10 heart assist devices implanted in calves for periods up to 35 weeks. At termination, each was examined to correlate blood compatibility and device performance with surface properties, chemical purity, physical stability and affinity for lipid absorption."} {"id": "PMID:170288", "title": "Soft tissue response to four dense ceramic materials and two clinically used biomaterials.", "content": "Disk-shaped implants of spinel, alumina, mullite, zircon, a cast Co-Cr-Mo alloy, and ultra-high molecular weight polyethylene (UHMWPE), were implanted in the paraspinalis muscle of 12 adult, male, white New Zealand rabbits. Prior to implantation the implants were characterized with respect to size and shape, weight and surface roughness. After periods of 1 month, 2 months, and 4 months, the rabbits were sacrificed and the tissue specimens were retrieved with the implants still intact. Histological examination of the tissues surrounding the implants along with changes in the size and shape, weight, and surface roughness of the implants were used as criteria for evaluating these materials for implant purposes. No surfaces degradation of any of the materials was detected using scanning electron microscopy. Fibrous tissue seemed to adhere to the UHMWPE implants more than any other material used in this study. Large amounts of fibrous tissue were also found to adhere to the cast Co-Cr-Mo alloy implants. The histological results indicated that within the limits of this investigation, the biocompatibility of the ceramic materials used in this study compared favorably with the clinically used Co-Cr-Mo alloy implants and the UHMWPE implants.", "contents": "Soft tissue response to four dense ceramic materials and two clinically used biomaterials. Disk-shaped implants of spinel, alumina, mullite, zircon, a cast Co-Cr-Mo alloy, and ultra-high molecular weight polyethylene (UHMWPE), were implanted in the paraspinalis muscle of 12 adult, male, white New Zealand rabbits. Prior to implantation the implants were characterized with respect to size and shape, weight and surface roughness. After periods of 1 month, 2 months, and 4 months, the rabbits were sacrificed and the tissue specimens were retrieved with the implants still intact. Histological examination of the tissues surrounding the implants along with changes in the size and shape, weight, and surface roughness of the implants were used as criteria for evaluating these materials for implant purposes. No surfaces degradation of any of the materials was detected using scanning electron microscopy. Fibrous tissue seemed to adhere to the UHMWPE implants more than any other material used in this study. Large amounts of fibrous tissue were also found to adhere to the cast Co-Cr-Mo alloy implants. The histological results indicated that within the limits of this investigation, the biocompatibility of the ceramic materials used in this study compared favorably with the clinically used Co-Cr-Mo alloy implants and the UHMWPE implants."} {"id": "PMID:170289", "title": "The interactions of thrombin with borosilicate glass surfaces.", "content": "Borosilicate glass (G) and commercial poly(methyl methacrylate) (PMM) surfaces were examined at pH 7, monovalent ionic strength 0.14 and 22 degrees C. Thrombin concentrations ranged from 6 X 10(-9) to 5.2 X 10(-8)M. Decreases in thrombin concentration in 10 ml vessles were determined by clotting time assay. Adsorption to PMM vessels is small. These were examined to establish the validity of the method. For G-vessels, the terminations of initial rapid decreases, associated with adsorption equilibrium, are accounted for mainly by an average isotherm having an association constant of 1.8 X 10(7) l./mol. Adsorption equilibrium is accompanied by a slower rate of decrease consistent with the surface denaturation of 2.5%/min of adsorbed molecules. Molecules remaining adsorbed to the surfaces of 1 mm i.d. G-capillaries were examined using the sequence of thrombin adsorption, buffer washing for times tw, removal of buffer and introduction of a fibrinogen aliquot for determination of effective surface thrombin concentration by a capillary clotting time. Most adsorbed molecules (less than 90%) essentially desorb within tw = 2 min, a second class (greater than 8%) desorb in tw similar to 30 min, and members of additional classes are still present after tw = 1440 min. For all of the properties examined, there is a small variance between vessels taken at the same time from the same batch, and a larger variance between groups of vessels taken at different times from the same batch or from different batches.", "contents": "The interactions of thrombin with borosilicate glass surfaces. Borosilicate glass (G) and commercial poly(methyl methacrylate) (PMM) surfaces were examined at pH 7, monovalent ionic strength 0.14 and 22 degrees C. Thrombin concentrations ranged from 6 X 10(-9) to 5.2 X 10(-8)M. Decreases in thrombin concentration in 10 ml vessles were determined by clotting time assay. Adsorption to PMM vessels is small. These were examined to establish the validity of the method. For G-vessels, the terminations of initial rapid decreases, associated with adsorption equilibrium, are accounted for mainly by an average isotherm having an association constant of 1.8 X 10(7) l./mol. Adsorption equilibrium is accompanied by a slower rate of decrease consistent with the surface denaturation of 2.5%/min of adsorbed molecules. Molecules remaining adsorbed to the surfaces of 1 mm i.d. G-capillaries were examined using the sequence of thrombin adsorption, buffer washing for times tw, removal of buffer and introduction of a fibrinogen aliquot for determination of effective surface thrombin concentration by a capillary clotting time. Most adsorbed molecules (less than 90%) essentially desorb within tw = 2 min, a second class (greater than 8%) desorb in tw similar to 30 min, and members of additional classes are still present after tw = 1440 min. For all of the properties examined, there is a small variance between vessels taken at the same time from the same batch, and a larger variance between groups of vessels taken at different times from the same batch or from different batches."} {"id": "PMID:170290", "title": "Studies on the regulation of the three enzymes of the Leloir pathway in cultured mammalian cells. II. A search for quantitative interrelationships between the three enzyme activities.", "content": "Studies on a normal human diploid cell strain revealed that the specific activity of the cell protein, for each of the three enzymes of the Leloir pathway, changed significantly as the cells grew. The kinetics of change in specific activity varied according to the enzyme being studied, and the kinetics for each enzyme varied from experiment to experiment. Within each experiment, there was no consistent correlation between specific activity for any one enzyme and specific activity for the other two. The ratios between the specific activities did not tend to remain constant as the absolute levels of specific activity changed. Hence, the activities did not behave coordinately. The kinetics of change in these ratios varied from experiment to experiment. The failure of galactose to stimulate increased cellular activity for the three enzymes (shown in the preceding paper), and the absence of a coordinate relationship between the activities, represent a striking difference between the behavior of these enzymes in human diploid cell strains and their behavior in E. coli.", "contents": "Studies on the regulation of the three enzymes of the Leloir pathway in cultured mammalian cells. II. A search for quantitative interrelationships between the three enzyme activities. Studies on a normal human diploid cell strain revealed that the specific activity of the cell protein, for each of the three enzymes of the Leloir pathway, changed significantly as the cells grew. The kinetics of change in specific activity varied according to the enzyme being studied, and the kinetics for each enzyme varied from experiment to experiment. Within each experiment, there was no consistent correlation between specific activity for any one enzyme and specific activity for the other two. The ratios between the specific activities did not tend to remain constant as the absolute levels of specific activity changed. Hence, the activities did not behave coordinately. The kinetics of change in these ratios varied from experiment to experiment. The failure of galactose to stimulate increased cellular activity for the three enzymes (shown in the preceding paper), and the absence of a coordinate relationship between the activities, represent a striking difference between the behavior of these enzymes in human diploid cell strains and their behavior in E. coli."} {"id": "PMID:170291", "title": "ITP pyrophosphohydrolase and IDP phosphohydrolase in rat tissue.", "content": "The existence of a nucleoside triphosphate pyrophosphohydrolase specific for ITP has been demonstrated in the cytosol fraction of a variety of rat tissues. The enzyme, stable to moderate heat treatment, was present in erythrocytes as well as brain, heart, kidney, liver, lung, muscle, ovaries, spleen, testes and thymus. The specific activity of the enzyme ranges from 26 to 150 mumoles/min/g protein. In addition, evidence is given for a heat labile nucleoside diphosphate (IDP) phosphohydrolase present in most rat tissues, and particularly high in the adrenal (137 mumoles/min/g protein). An \"ITP-IMP cycle\" is proposed as a rgulating mechanism for intracellular levels of ATP.", "contents": "ITP pyrophosphohydrolase and IDP phosphohydrolase in rat tissue. The existence of a nucleoside triphosphate pyrophosphohydrolase specific for ITP has been demonstrated in the cytosol fraction of a variety of rat tissues. The enzyme, stable to moderate heat treatment, was present in erythrocytes as well as brain, heart, kidney, liver, lung, muscle, ovaries, spleen, testes and thymus. The specific activity of the enzyme ranges from 26 to 150 mumoles/min/g protein. In addition, evidence is given for a heat labile nucleoside diphosphate (IDP) phosphohydrolase present in most rat tissues, and particularly high in the adrenal (137 mumoles/min/g protein). An \"ITP-IMP cycle\" is proposed as a rgulating mechanism for intracellular levels of ATP."} {"id": "PMID:170292", "title": "The effect of serum on the transport and phosphorylation of 2-deoxyglucose by untransformed and transformed mouse 3T3 cells.", "content": "Serum starvation of growing and nongrowing (density-inhibited) mouse 3T3 cells resulted in decreased phosphorylation of 2-deoxy--D-glucose, while the time course of transport of this sugar remained unchanged. Serum starvation of SV40 transformed 3T3 cells (SV101) and spontaneously transformed 3T6 cells did not alter either the time course of transport, or phosphorylation of the sugar. Treatment of SV101 cells with 10(-4) M dibutyryl adenosine cyclic 3':5' monophosphate and 10(-3) M theophylline did not restore the capacity to regulate 2-deoxy-D-glucose phosphorylation when these cells were serum deprived. We conclude that serum factors are involved in the modulation of phosphorylation of 2-deoxy-D-glucose in 3T3 cells rather than its transport. This regulation is operative both in growing as well as nongrowing 3T3 cells. In contrast, transformed cells do not respond to this regulation of 2-deoxy-D-glucose phosphorylation.", "contents": "The effect of serum on the transport and phosphorylation of 2-deoxyglucose by untransformed and transformed mouse 3T3 cells. Serum starvation of growing and nongrowing (density-inhibited) mouse 3T3 cells resulted in decreased phosphorylation of 2-deoxy--D-glucose, while the time course of transport of this sugar remained unchanged. Serum starvation of SV40 transformed 3T3 cells (SV101) and spontaneously transformed 3T6 cells did not alter either the time course of transport, or phosphorylation of the sugar. Treatment of SV101 cells with 10(-4) M dibutyryl adenosine cyclic 3':5' monophosphate and 10(-3) M theophylline did not restore the capacity to regulate 2-deoxy-D-glucose phosphorylation when these cells were serum deprived. We conclude that serum factors are involved in the modulation of phosphorylation of 2-deoxy-D-glucose in 3T3 cells rather than its transport. This regulation is operative both in growing as well as nongrowing 3T3 cells. In contrast, transformed cells do not respond to this regulation of 2-deoxy-D-glucose phosphorylation."} {"id": "PMID:170293", "title": "The role of cyclic AMP in myogenesis.", "content": "The effect of exogenously administered cyclic AMP derivatives and of endogenously elevated cyclic AMP levels on the spontaneous fusion of skeletal muscle myoblasts has been investigated. Contrary to earlier reports, cAMP does not appear to have a direct inhibitory effect on the fusion of an established line (L8) of rat myoblasts. Similarly, cAMP did not block the fusion of primary chick myoblasts. However, fusion of the rat myoblasts was prevented when the cAMP induced inhibition of growth prevented the cells from reaching the \"critical\" cell density necessary for fusion.", "contents": "The role of cyclic AMP in myogenesis. The effect of exogenously administered cyclic AMP derivatives and of endogenously elevated cyclic AMP levels on the spontaneous fusion of skeletal muscle myoblasts has been investigated. Contrary to earlier reports, cAMP does not appear to have a direct inhibitory effect on the fusion of an established line (L8) of rat myoblasts. Similarly, cAMP did not block the fusion of primary chick myoblasts. However, fusion of the rat myoblasts was prevented when the cAMP induced inhibition of growth prevented the cells from reaching the \"critical\" cell density necessary for fusion."} {"id": "PMID:170294", "title": "Studies on the regulation of the three enzymes of the Leloir pathway in cultured mammalian cells. I. Effect of substitution of galactose for glucose as the sole hexose in the medium in human diploid cell strains and in a rat hepatoma line.", "content": "In human diploid cell strains, the substitution of galactose for glucose as the sole hexose in the medium had no measurable effect on the specific activity of the cell protein for any of the three enzymes of the Leloir pathway. These enzymes are galactokinase, alpha-D-galactose-1-phosphate: UDP glucose uridyl transferase and UDP galactose 4-epimerase. A cell strain from a patient with galactosemia had no detectable activity for the transferase. The substitution of galactose for glucose in the medium of these cells (which has been shown to cause the cells to accumulate galactose-1-phosphate) also failed to affect cellular activity for the three enzymes. Similarly, the three activities failed to respond to the substitution of galactose for glucose in cultures of a rat hepatoma line. Cells of this line have been shown by others to perform a number of the tissue-specific functions of liver. The failure of galactose to stimulate increasd cellular activity for the three enzymes represents a striking difference between the behavior of these enzymes in human diploid cell strains and their behavior in E. coli.", "contents": "Studies on the regulation of the three enzymes of the Leloir pathway in cultured mammalian cells. I. Effect of substitution of galactose for glucose as the sole hexose in the medium in human diploid cell strains and in a rat hepatoma line. In human diploid cell strains, the substitution of galactose for glucose as the sole hexose in the medium had no measurable effect on the specific activity of the cell protein for any of the three enzymes of the Leloir pathway. These enzymes are galactokinase, alpha-D-galactose-1-phosphate: UDP glucose uridyl transferase and UDP galactose 4-epimerase. A cell strain from a patient with galactosemia had no detectable activity for the transferase. The substitution of galactose for glucose in the medium of these cells (which has been shown to cause the cells to accumulate galactose-1-phosphate) also failed to affect cellular activity for the three enzymes. Similarly, the three activities failed to respond to the substitution of galactose for glucose in cultures of a rat hepatoma line. Cells of this line have been shown by others to perform a number of the tissue-specific functions of liver. The failure of galactose to stimulate increasd cellular activity for the three enzymes represents a striking difference between the behavior of these enzymes in human diploid cell strains and their behavior in E. coli."} {"id": "PMID:170295", "title": "Lipid metabolism in pregnancy. II. Altered lipid composition in intermediage, very low, low and high-density lipoprotein fractions.", "content": "The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus.", "contents": "Lipid metabolism in pregnancy. II. Altered lipid composition in intermediage, very low, low and high-density lipoprotein fractions. The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus."} {"id": "PMID:170296", "title": "Transmembrane potentials and steroidogenesis in normal and neoplastic human adrenocortical tissue.", "content": "Trans-membrane potentials and steroidogenesis were measured in superfused slices of non-tumor and neoplastic human adrenocortical tissue. Non-tumor tissue was obtained at the time for renal transplant or from tissue removed along with tumors. Non-tumor human adrenocortical tissue had electrophysiological and steroidogenic properties similar to those of the rat and rabbit. In normal medium ACTH stimulated steroidogenesis but had no effect on the membrane potential. In K+-free medium, the cells hyperpolarized, and subsequent addition of ACTH caused depolarization. Trans-membrane potentials of adrenocortical tumors were lower than those of non-tumor cells. Ommission of K+ from the medium caused hyperpolairzation of the tumor cells, but the trans-membrane potentials did not reach the values of hyperpolarized non-tumor cells. ACTH, added to the K+-free medium, caused little or no change in membrane potential of tumor cells except in one case of a virilizing adenoma, which responded very much like non-tumor tissue. Except for the virilizing adenoma, tumor tissue slices produced little or no detectable fluorogenic steroid, even in the presence of large amounts of ACTH or cyclic AMP. The virilizing adenoma responded with increased steroidogensis to ACTH and cyclic AMP.", "contents": "Transmembrane potentials and steroidogenesis in normal and neoplastic human adrenocortical tissue. Trans-membrane potentials and steroidogenesis were measured in superfused slices of non-tumor and neoplastic human adrenocortical tissue. Non-tumor tissue was obtained at the time for renal transplant or from tissue removed along with tumors. Non-tumor human adrenocortical tissue had electrophysiological and steroidogenic properties similar to those of the rat and rabbit. In normal medium ACTH stimulated steroidogenesis but had no effect on the membrane potential. In K+-free medium, the cells hyperpolarized, and subsequent addition of ACTH caused depolarization. Trans-membrane potentials of adrenocortical tumors were lower than those of non-tumor cells. Ommission of K+ from the medium caused hyperpolairzation of the tumor cells, but the trans-membrane potentials did not reach the values of hyperpolarized non-tumor cells. ACTH, added to the K+-free medium, caused little or no change in membrane potential of tumor cells except in one case of a virilizing adenoma, which responded very much like non-tumor tissue. Except for the virilizing adenoma, tumor tissue slices produced little or no detectable fluorogenic steroid, even in the presence of large amounts of ACTH or cyclic AMP. The virilizing adenoma responded with increased steroidogensis to ACTH and cyclic AMP."} {"id": "PMID:170297", "title": "Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism.", "content": "Although ratios of urinary cyclic AMP (cAMP) to creatinine were found in this study to be elevated in hyperthyroidism, as previously reported, this elevation appears to result primarily from a decrease in the rate of urinary creatinine excretion associated with the hyperthyroid state and not to be due to an increase in the urinary cAMP production rate. Indeed, there was no significant alteration observed in the urinary cAMP excretion found in 15 hyper-, 12 eu-, and 5 hypothyroid subjects. However, a slight, but significant increase in the 24-hour urinary cAMP excretion was noted in ambulating hyperthyroid subjects (8.5 +/- 2.4 muMol/day; normal 5.2 +/- 1.6 muMol/day; P less than .05). In contrast, the effect of the infusion of 0.05 mug/kg/min of epinephrine over a 2-hour period, resulted in a significantly greater rise in urinary cAMP excretion in hyperthyroid patients (0.83 +/- 0.07 muMol/h) compared to euthyroid subjects (0.53 +/- 0.4 muMol/h; P less than .005). Furthermore, hypothyroid subjects had no significant rise in urinary cAMP excretion after epinephrine infusion (P less than .001). Cardiovascular end-organ response to the epinephrine infusion was also greater in the hyperthyroid subjects and virtually absent in the hypothyroid group. These results suggest that there may be a significant alteration in the cAMP generating systems in states of thyroid hormone excess or insufficiency, and that provocative stimuli, such as epinephrine, may have its end-organ response modified by thyroid hormone effects on adenylate cyclase-cyclic AMP generating systems.", "contents": "Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism. Although ratios of urinary cyclic AMP (cAMP) to creatinine were found in this study to be elevated in hyperthyroidism, as previously reported, this elevation appears to result primarily from a decrease in the rate of urinary creatinine excretion associated with the hyperthyroid state and not to be due to an increase in the urinary cAMP production rate. Indeed, there was no significant alteration observed in the urinary cAMP excretion found in 15 hyper-, 12 eu-, and 5 hypothyroid subjects. However, a slight, but significant increase in the 24-hour urinary cAMP excretion was noted in ambulating hyperthyroid subjects (8.5 +/- 2.4 muMol/day; normal 5.2 +/- 1.6 muMol/day; P less than .05). In contrast, the effect of the infusion of 0.05 mug/kg/min of epinephrine over a 2-hour period, resulted in a significantly greater rise in urinary cAMP excretion in hyperthyroid patients (0.83 +/- 0.07 muMol/h) compared to euthyroid subjects (0.53 +/- 0.4 muMol/h; P less than .005). Furthermore, hypothyroid subjects had no significant rise in urinary cAMP excretion after epinephrine infusion (P less than .001). Cardiovascular end-organ response to the epinephrine infusion was also greater in the hyperthyroid subjects and virtually absent in the hypothyroid group. These results suggest that there may be a significant alteration in the cAMP generating systems in states of thyroid hormone excess or insufficiency, and that provocative stimuli, such as epinephrine, may have its end-organ response modified by thyroid hormone effects on adenylate cyclase-cyclic AMP generating systems."} {"id": "PMID:170298", "title": "Excretion of 2-hydroxyestrone in urine throughout human pregnancies.", "content": "Urinary 2-hydroxyesterone was quantitatively determined in the course of several normal human pregnancies. The urine was subjected to hot acid hydrolysis and after chromatographic purification, 2-hydroxyesterone was converted into the corresponding phenazine derivative, which was submitted to a final column chromatogrphy and then quantitated by UV-spectrometry. For correction of procedural losses 2-hydroxyestrone-4-14C was used as internal standard. The urinary 2-hydroxyestrone of different subjects varied within a wide range especially at mid-pregnancy between 100 and 2500 mug/24 h. The day-to-day variation of the excretion of 2-hydroxyestrone was mostly less than 30% of the total value of that day, but sometimes could even reach 60%. The investigation of 2-hydroxyestrone and total estrogens at regular intervals throughout several pregnancies, showed that the excretion of 2-hydroxyesterone generally reached a maximum during the second trimester, while the excretion of the total estrogens steadily increased up to parturition. When analyzing the urines of different subjects during the last 4 months of pregnancy, no correlation appeared to exist for the excretions of the total estrogens and of 2-hydroxyestrone.", "contents": "Excretion of 2-hydroxyestrone in urine throughout human pregnancies. Urinary 2-hydroxyesterone was quantitatively determined in the course of several normal human pregnancies. The urine was subjected to hot acid hydrolysis and after chromatographic purification, 2-hydroxyesterone was converted into the corresponding phenazine derivative, which was submitted to a final column chromatogrphy and then quantitated by UV-spectrometry. For correction of procedural losses 2-hydroxyestrone-4-14C was used as internal standard. The urinary 2-hydroxyestrone of different subjects varied within a wide range especially at mid-pregnancy between 100 and 2500 mug/24 h. The day-to-day variation of the excretion of 2-hydroxyestrone was mostly less than 30% of the total value of that day, but sometimes could even reach 60%. The investigation of 2-hydroxyestrone and total estrogens at regular intervals throughout several pregnancies, showed that the excretion of 2-hydroxyesterone generally reached a maximum during the second trimester, while the excretion of the total estrogens steadily increased up to parturition. When analyzing the urines of different subjects during the last 4 months of pregnancy, no correlation appeared to exist for the excretions of the total estrogens and of 2-hydroxyestrone."} {"id": "PMID:170299", "title": "A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty.", "content": "Nineteen boys with true isolated growth hormone deficiency developed the first stages of puberty at an average bone age of 12.0\"years\" (Tanner Whitehouse Method 2, RUS score). The average chronological age was 15.0 years. Seven similar girls entered puberty at 10.9\"years\" in bone age and 13.7 years in chronological age. The means and ranges of bone age at beginning of puberty of these patients are very close to those of normal children.", "contents": "A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty. Nineteen boys with true isolated growth hormone deficiency developed the first stages of puberty at an average bone age of 12.0\"years\" (Tanner Whitehouse Method 2, RUS score). The average chronological age was 15.0 years. Seven similar girls entered puberty at 10.9\"years\" in bone age and 13.7 years in chronological age. The means and ranges of bone age at beginning of puberty of these patients are very close to those of normal children."} {"id": "PMID:170300", "title": "Isolation of infectious bovine rhinotracheitis virus from Mustelidae.", "content": "Herpesviruses isolated from either domesticated or wild carnivores should be immunologically compared with known viruses of this group which could have been included in the diet of the animal before being considered to be previously undescribed herpesviruses native to the carnivore in question.", "contents": "Isolation of infectious bovine rhinotracheitis virus from Mustelidae. Herpesviruses isolated from either domesticated or wild carnivores should be immunologically compared with known viruses of this group which could have been included in the diet of the animal before being considered to be previously undescribed herpesviruses native to the carnivore in question."} {"id": "PMID:170301", "title": "Production of human lymphoblastoid interferon.", "content": "The interferon response of 21 lines of human lymphoblasts varied greatly. Interferon from the best producer (11,000 U/ml) resembled human leukocyte interferon.", "contents": "Production of human lymphoblastoid interferon. The interferon response of 21 lines of human lymphoblasts varied greatly. Interferon from the best producer (11,000 U/ml) resembled human leukocyte interferon."} {"id": "PMID:170302", "title": "Influence of oxygen and culture media on maintenance of whole hamster trachea organ cultures and replication of Sendai virus.", "content": "Effects of various oxygen concentrations and culture media on the maintenance of 4-day-old hamster trachea organ cultures and the yield of Sendai virus were studied. The basic media used were Eagle minimal essential medium, medium 199, and CMRL 1066 supplemented with glutamine and antibiotics and buffered with NaHCO3 or N-2-hydroxyethyl-piperazine-N'-2'-ethanesulfonic acid (HEPES). In addition, each medium was evaluated under a gas phase of 5% CO2 and 95% O2, 5% CO2 and 45% O2 and 50% N2, or 5% CO2 and 95% air. Culturing of explants with CMRL 1066 and medium 199 buffered with HEPES in the presence of 5% CO2 and air proved most efficient; ciliary movement and ciliated surface epithelium were maintained for periods up to 27 days. No significant difference in the rate of replication of Sendai virus was seen in the three different media with the two buffer systems in the three different gaseous phases. The addition of 0.2% bovine serum albumin to the media yielded greater quantities of virus, up to 200-fold increase in titer without producing changes in ciliary function. A distinctive pattern of morphological changes was observed in explants of trachea epithelia inoculated with Sendai virus. These results suggest the practical application in the use of whole hamster trachea explants as a diagnostic aid in the isolation of Sendai virus from laboratory rodents.", "contents": "Influence of oxygen and culture media on maintenance of whole hamster trachea organ cultures and replication of Sendai virus. Effects of various oxygen concentrations and culture media on the maintenance of 4-day-old hamster trachea organ cultures and the yield of Sendai virus were studied. The basic media used were Eagle minimal essential medium, medium 199, and CMRL 1066 supplemented with glutamine and antibiotics and buffered with NaHCO3 or N-2-hydroxyethyl-piperazine-N'-2'-ethanesulfonic acid (HEPES). In addition, each medium was evaluated under a gas phase of 5% CO2 and 95% O2, 5% CO2 and 45% O2 and 50% N2, or 5% CO2 and 95% air. Culturing of explants with CMRL 1066 and medium 199 buffered with HEPES in the presence of 5% CO2 and air proved most efficient; ciliary movement and ciliated surface epithelium were maintained for periods up to 27 days. No significant difference in the rate of replication of Sendai virus was seen in the three different media with the two buffer systems in the three different gaseous phases. The addition of 0.2% bovine serum albumin to the media yielded greater quantities of virus, up to 200-fold increase in titer without producing changes in ciliary function. A distinctive pattern of morphological changes was observed in explants of trachea epithelia inoculated with Sendai virus. These results suggest the practical application in the use of whole hamster trachea explants as a diagnostic aid in the isolation of Sendai virus from laboratory rodents."} {"id": "PMID:170303", "title": "Simplified scheme for routine identification of human Staphylococcus species.", "content": "From a total of 40 characters that were previously used to differentiate species of staphylococci, 13 key characters were selected to make a simplified scheme that could be easily used by the routine clinical laboratory for identifying human staphylococci. These key characters included coagulase activity, hemolysis, nitrate reduction, and aerobic acid production from fructose, xylose, arabinose, ribose, maltose, lactose, sucrose, trehalose, mannitol, and xylitol. In the simplified scheme, 924 strains of staphylococci were placed into 11 positions, each of which contained the major portion (greater than or equal to 80%) of strains of one of the recognized species. Several positions contained a rare or few uncommon strains of one or more additional species and these could be resolved on the basis of other key characters.", "contents": "Simplified scheme for routine identification of human Staphylococcus species. From a total of 40 characters that were previously used to differentiate species of staphylococci, 13 key characters were selected to make a simplified scheme that could be easily used by the routine clinical laboratory for identifying human staphylococci. These key characters included coagulase activity, hemolysis, nitrate reduction, and aerobic acid production from fructose, xylose, arabinose, ribose, maltose, lactose, sucrose, trehalose, mannitol, and xylitol. In the simplified scheme, 924 strains of staphylococci were placed into 11 positions, each of which contained the major portion (greater than or equal to 80%) of strains of one of the recognized species. Several positions contained a rare or few uncommon strains of one or more additional species and these could be resolved on the basis of other key characters."} {"id": "PMID:170304", "title": "New satellitism test for isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae in sputum.", "content": "A new satellitism test designed to facilitate the isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae is described. In the basal medium, nicotinamide adenine dinucleotide is incorporated at a concentration of 0.2 mug per ml, an amount adequate for H. influenzae but not for H. parainfluenzae. Two disks are placed on the surface of the medium, one disk being impregnated with 60 mug of hemin and the other with 15 mug of nicotinamide adenine dinucleotide. Under these conditions, H. influenzae strains grow around the hemin disk only and the majority of H. parainfluenzae grow around the nicotinamide adenine dinucleotide disk. This procedure gives results which are more clear cut than other established methods, especially in sputum culture.", "contents": "New satellitism test for isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae in sputum. A new satellitism test designed to facilitate the isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae is described. In the basal medium, nicotinamide adenine dinucleotide is incorporated at a concentration of 0.2 mug per ml, an amount adequate for H. influenzae but not for H. parainfluenzae. Two disks are placed on the surface of the medium, one disk being impregnated with 60 mug of hemin and the other with 15 mug of nicotinamide adenine dinucleotide. Under these conditions, H. influenzae strains grow around the hemin disk only and the majority of H. parainfluenzae grow around the nicotinamide adenine dinucleotide disk. This procedure gives results which are more clear cut than other established methods, especially in sputum culture."} {"id": "PMID:170305", "title": "Improved Epstein-Barr virus immunoglobulin M antibody test.", "content": "The successful demonstration of Epstein-Barr virus immunoglobulin M (EBV IgM) antibody in human sera has been accomplished to date by at least four groups of workers. Many, however, including ourselves, have had difficulty in getting reproducible results with the techniques described. The three-coat technique described by H. Schmitz and M. Scherer (1972) on both fractionated and unfractioned sera was adopted with minor modifications. The Hyland antihuman IgM antiserum used in the second coat was made specific by absorption on Cohn fraction II. This step in the procedure was found to be the single most important factor in arriving at reproducible results in the IgM test. The EBV IgM antibodies from our results to date with this method in 14 cases of heterophil-positive cases of mononucleosis appear short lived, lasting 2 months or less. These antibodies were found in only 2 of 18 selected non-mononucleosis cases, in both associated with EBV-viral capsid antigen antibody rise or seroconversion. The successful elimination of nonspecific fluorescence by a simple, inexpensive procedure and the possibility of testing unabsorbed, unfractionated sera directly will facilitate the use oe the EBV IgM antibody test in the future.", "contents": "Improved Epstein-Barr virus immunoglobulin M antibody test. The successful demonstration of Epstein-Barr virus immunoglobulin M (EBV IgM) antibody in human sera has been accomplished to date by at least four groups of workers. Many, however, including ourselves, have had difficulty in getting reproducible results with the techniques described. The three-coat technique described by H. Schmitz and M. Scherer (1972) on both fractionated and unfractioned sera was adopted with minor modifications. The Hyland antihuman IgM antiserum used in the second coat was made specific by absorption on Cohn fraction II. This step in the procedure was found to be the single most important factor in arriving at reproducible results in the IgM test. The EBV IgM antibodies from our results to date with this method in 14 cases of heterophil-positive cases of mononucleosis appear short lived, lasting 2 months or less. These antibodies were found in only 2 of 18 selected non-mononucleosis cases, in both associated with EBV-viral capsid antigen antibody rise or seroconversion. The successful elimination of nonspecific fluorescence by a simple, inexpensive procedure and the possibility of testing unabsorbed, unfractionated sera directly will facilitate the use oe the EBV IgM antibody test in the future."} {"id": "PMID:170306", "title": "Methods for the detection of viruses in bovine serum.", "content": "An evaluation of selected commonly used procedures for the recovery of endogenous viral contaminants in bovine serum was undertaken. Low speen centrifugation (25,000 x g) was found to be efficient for the recovery of bovine herpesvirus type 1 (BHV-1) and parainfluenza virus type 3(PI-3) in bovine serum. Decreased infectivity titers were obtained when parainfluenza virus type 3, and to a lesser extent bovine herpes virus type 1, were concentrated using high speed centrifugation (100,000 x g) for extended time periods. In neither case could infectious virus be recovered from serum containing sufficient titers of homologous neutralizing antibody, although electron microscopy examination revealed the presence of the viruses previously added. In the presence of homologous antibody, virus particles appeared to have a diffuse, poorly defined outer membrane. Neutralizing antibody titers to bovine herpesvirus type 1 and outer membrane. Neutralizing antibody titers to bovine herpesvirus type 1 and parainfluenza virus types were found in fetal, calf, and adult bovine sera. The prevalence and magnitude of the antibody titers to these viruses increased with the age of the animals examined.", "contents": "Methods for the detection of viruses in bovine serum. An evaluation of selected commonly used procedures for the recovery of endogenous viral contaminants in bovine serum was undertaken. Low speen centrifugation (25,000 x g) was found to be efficient for the recovery of bovine herpesvirus type 1 (BHV-1) and parainfluenza virus type 3(PI-3) in bovine serum. Decreased infectivity titers were obtained when parainfluenza virus type 3, and to a lesser extent bovine herpes virus type 1, were concentrated using high speed centrifugation (100,000 x g) for extended time periods. In neither case could infectious virus be recovered from serum containing sufficient titers of homologous neutralizing antibody, although electron microscopy examination revealed the presence of the viruses previously added. In the presence of homologous antibody, virus particles appeared to have a diffuse, poorly defined outer membrane. Neutralizing antibody titers to bovine herpesvirus type 1 and outer membrane. Neutralizing antibody titers to bovine herpesvirus type 1 and parainfluenza virus types were found in fetal, calf, and adult bovine sera. The prevalence and magnitude of the antibody titers to these viruses increased with the age of the animals examined."} {"id": "PMID:170307", "title": "Increased selectivity of Mitis-Salivarius agar containing polymyxin.", "content": "Incorporation of the antibiotic polymixin B sulfate in plates of Mitis-Salivarius medium at a level of 100 U per ml effectively suppressed the growth of gram-negative spreading organisms which occasionally overgrow Mitis-Salivarius plates of oral samples and make them unsuitable for enumeration and differentiation of streptococci. At the indicated level the antibiotic did not affect the growth or typical colonial characteristics of the oral streptococci.", "contents": "Increased selectivity of Mitis-Salivarius agar containing polymyxin. Incorporation of the antibiotic polymixin B sulfate in plates of Mitis-Salivarius medium at a level of 100 U per ml effectively suppressed the growth of gram-negative spreading organisms which occasionally overgrow Mitis-Salivarius plates of oral samples and make them unsuitable for enumeration and differentiation of streptococci. At the indicated level the antibiotic did not affect the growth or typical colonial characteristics of the oral streptococci."} {"id": "PMID:170308", "title": "Complement-fixing antibody in human sera reactive with viral and soluble antigens of cytomegalovirus.", "content": "Antibody titers to cytomegalovirus were determined in 204 single-serum specimens and in 138 serum pairs, utilizing as antigen extracts of infected cells prepared by either freezing and thawing cells (FT antigen) or extracting them with a glycine buffer (GE antigen). With the serum pairs, 40% of the early sera and 44% of the late sera showed a fourfold or higher antibody titer with the GE antigen compared with those with the FT antigen, whereas 39% of the single sera had a fourfold or higher titer with the GE antigen. Sucrose density gradient centrifugation of the two antigen preparations indicated that the GE antigen contained two peaks of complement-fixing activity, one at a density of 1.18 to 1.22 g/cm3 and one at 1.06 to 1.10 g/cm3. The FT antigen had only one discernible peak of complement-fixing activity at 1.04 to 1.10 g/cm3. On electron microscopy, the more dense peak contained mainly nucleocapsids with some dense bodies and occasional enveloped virions, and the lighter peak was composed of amorphous material. Antibody titers obtained with the crude GE antigen and the more dense peak (designated viral antigen) were in agreement, whereas titers with the FT antigen agreed with those obtained with the lighter peak (soluble antigen). The antibody detected with both antigens was mainly immunoglobulin G.", "contents": "Complement-fixing antibody in human sera reactive with viral and soluble antigens of cytomegalovirus. Antibody titers to cytomegalovirus were determined in 204 single-serum specimens and in 138 serum pairs, utilizing as antigen extracts of infected cells prepared by either freezing and thawing cells (FT antigen) or extracting them with a glycine buffer (GE antigen). With the serum pairs, 40% of the early sera and 44% of the late sera showed a fourfold or higher antibody titer with the GE antigen compared with those with the FT antigen, whereas 39% of the single sera had a fourfold or higher titer with the GE antigen. Sucrose density gradient centrifugation of the two antigen preparations indicated that the GE antigen contained two peaks of complement-fixing activity, one at a density of 1.18 to 1.22 g/cm3 and one at 1.06 to 1.10 g/cm3. The FT antigen had only one discernible peak of complement-fixing activity at 1.04 to 1.10 g/cm3. On electron microscopy, the more dense peak contained mainly nucleocapsids with some dense bodies and occasional enveloped virions, and the lighter peak was composed of amorphous material. Antibody titers obtained with the crude GE antigen and the more dense peak (designated viral antigen) were in agreement, whereas titers with the FT antigen agreed with those obtained with the lighter peak (soluble antigen). The antibody detected with both antigens was mainly immunoglobulin G."} {"id": "PMID:170309", "title": "Detection by radioimmunoassay of antibodies in human smallpox patients and vaccinees.", "content": "A radioimmunoassay procedure was developed for determining smallpox and vaccinia antibodies in human sera. The test detected and measured both primary and secondary immune responses in persons infected with variola virus or vaccinia virus. The antibody titers obtained by complement fixation, hemagglutination inhibition, plaque reduction neutralization, and radioimmunoassay methods were compared. In sequential serum specimens, the radioimmunoassay test indicated fourfold or greater increases in all of the smallpox patients and in six of eight vaccinated persons. Both the complement fixation and the hemagglutination inhibition tests were less effective. In persons who had been vaccinated, radioimmunoassay and plaque reduction neutralization tests appeared to measure the same immune response. However, in smallpox patients the immune response was readily detected by radioimmunoassay, whereas an immune response was not detected by the plaque reduction neutralization test when vaccinia virus was the antigen in the test system. Radioimmunoassay is an operationally simple procedure which provides objective and quantitative end-point titers in serological determinations.", "contents": "Detection by radioimmunoassay of antibodies in human smallpox patients and vaccinees. A radioimmunoassay procedure was developed for determining smallpox and vaccinia antibodies in human sera. The test detected and measured both primary and secondary immune responses in persons infected with variola virus or vaccinia virus. The antibody titers obtained by complement fixation, hemagglutination inhibition, plaque reduction neutralization, and radioimmunoassay methods were compared. In sequential serum specimens, the radioimmunoassay test indicated fourfold or greater increases in all of the smallpox patients and in six of eight vaccinated persons. Both the complement fixation and the hemagglutination inhibition tests were less effective. In persons who had been vaccinated, radioimmunoassay and plaque reduction neutralization tests appeared to measure the same immune response. However, in smallpox patients the immune response was readily detected by radioimmunoassay, whereas an immune response was not detected by the plaque reduction neutralization test when vaccinia virus was the antigen in the test system. Radioimmunoassay is an operationally simple procedure which provides objective and quantitative end-point titers in serological determinations."} {"id": "PMID:170310", "title": "Diagnosis of Herpesvirus hominis infections in a general hospital laboratory.", "content": "There is a greatly increased interest in Herpesvirus hominis infections especially those of type 2 associated with genital lesions or neonatal disease. Physicians are eager to confirm the clinical impression with a specific virologic diagnosis such as isolation of the agent and its typing, and type-specific antibody responses. Procedures are reviewed here which permit such studies in general microbiology laboratories equipped for simple cell culture and immunofluorescence. This paper recounts experience with several laboratory methods and evaluates their efficiency and practicability in a general laboratory. Virus isolation was optimal if specimens were obtained from visible lesions early in their evolution and it often provided a specific diagnosis, including typing of the isolate by immunofluorescence, within 24 to 48 h. Estimation of serum antibodies to herpes simplex virus type 1 and 2 by indirect immunofluorescence was more sensitive and perhaps also more specific than by microneutralization test. A pilot study of herpes simplex virus antibody titers in mothers and in the cord blood of the offspring suggested the need to evaluate a possible protective role of high titer antibody in the fetus.", "contents": "Diagnosis of Herpesvirus hominis infections in a general hospital laboratory. There is a greatly increased interest in Herpesvirus hominis infections especially those of type 2 associated with genital lesions or neonatal disease. Physicians are eager to confirm the clinical impression with a specific virologic diagnosis such as isolation of the agent and its typing, and type-specific antibody responses. Procedures are reviewed here which permit such studies in general microbiology laboratories equipped for simple cell culture and immunofluorescence. This paper recounts experience with several laboratory methods and evaluates their efficiency and practicability in a general laboratory. Virus isolation was optimal if specimens were obtained from visible lesions early in their evolution and it often provided a specific diagnosis, including typing of the isolate by immunofluorescence, within 24 to 48 h. Estimation of serum antibodies to herpes simplex virus type 1 and 2 by indirect immunofluorescence was more sensitive and perhaps also more specific than by microneutralization test. A pilot study of herpes simplex virus antibody titers in mothers and in the cord blood of the offspring suggested the need to evaluate a possible protective role of high titer antibody in the fetus."} {"id": "PMID:170311", "title": "Inhibition of growth of Coccidioides immitis on Sabouraud medium containing polymyxin B.", "content": "No growth of Coccidioides immitis occurred when fluid from infected tissue or arthrospores suspended in distilled water were plated on the surface of Sabouraud medium, solidified with refined agar, and containing 20 mg of polymyxin B per liter. Solidification of Sabouraud medium with unrefined agar completely abolished the anticoccidioidal activity of polymyxin B.", "contents": "Inhibition of growth of Coccidioides immitis on Sabouraud medium containing polymyxin B. No growth of Coccidioides immitis occurred when fluid from infected tissue or arthrospores suspended in distilled water were plated on the surface of Sabouraud medium, solidified with refined agar, and containing 20 mg of polymyxin B per liter. Solidification of Sabouraud medium with unrefined agar completely abolished the anticoccidioidal activity of polymyxin B."} {"id": "PMID:170312", "title": "Antibodies to Epstein-Barr virus in patients with cryptococcosis.", "content": "Antibody levels to the Epstein-Barr virus, the etiological agent for heterophile-positive infectious mononucleosis, have been demonstrated in high titer in a number of lymphomas as well as infectious mononucleosis. Recent reports have suggested that the elevated antibody levels to Epstein-Barr virus may be the nonspecific result of disordered cell-mediated immunity. This study of patients with cryptococcosis was therefore undertaken to examine another disorder of known etiology associated with a defect in cell-mediated immunity. In this study we found that antibody levels in cryptococcosis patients, including a group specifically demonstrated to be anergic to a series of skin test antigens, were no different than those in matched normal controls. At the present time, therefore, it is unlikely that elevated antibody levels can be explained solely on the basis of depressed cellular immunity.", "contents": "Antibodies to Epstein-Barr virus in patients with cryptococcosis. Antibody levels to the Epstein-Barr virus, the etiological agent for heterophile-positive infectious mononucleosis, have been demonstrated in high titer in a number of lymphomas as well as infectious mononucleosis. Recent reports have suggested that the elevated antibody levels to Epstein-Barr virus may be the nonspecific result of disordered cell-mediated immunity. This study of patients with cryptococcosis was therefore undertaken to examine another disorder of known etiology associated with a defect in cell-mediated immunity. In this study we found that antibody levels in cryptococcosis patients, including a group specifically demonstrated to be anergic to a series of skin test antigens, were no different than those in matched normal controls. At the present time, therefore, it is unlikely that elevated antibody levels can be explained solely on the basis of depressed cellular immunity."} {"id": "PMID:170313", "title": "New human adenovirus isolated from a renal transplant recipient: description and characterization of candiate adenovirus type 34.", "content": "An antigenically distinct adenovirus is described which was isolated in March 1972 from the urine of a 17-year-old Caucasian male who was experiencing fever after receiving a kidney transplant from a cadaver in February. The adenovirus could not be isolated in April from a pharyngeal swab which yielded cytomegalovirus. Complement-fixation, hemagglutination-inhibition, and/or serum-neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred during March and showed that infections with cytomegalovirus and respiratory syncytial virus also occurred during late March and April. The patient's persistent fever, for which other causes could not be found, may have been associated with one or more of these infections. Upper respiratory symptoms and lung involvement were not found during this period. Mild liver dysfunction during this time could not be clearly related to adenovirus infection because of the presence of multiple other causes. The adenovirus may have been latent in the donor kidney and become active in the new host as a consequence of immunological impairment. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group IA. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1.304 g/ml for the group CF antigen (hexon), 1.295 g/ml for the major soluble complete hemagglutinin (dodecon), and 1.206 g/ml for the minor soluble complete hemagglutinin (tentatively, fiber dimer). The virus does not cross-react in reciprocal hemagglutination-inhibition and serum-neutralization tests with antisera to adenovirus types 1 to 33. We propose this virus as candidate adenovirus type 34 (Compton).", "contents": "New human adenovirus isolated from a renal transplant recipient: description and characterization of candiate adenovirus type 34. An antigenically distinct adenovirus is described which was isolated in March 1972 from the urine of a 17-year-old Caucasian male who was experiencing fever after receiving a kidney transplant from a cadaver in February. The adenovirus could not be isolated in April from a pharyngeal swab which yielded cytomegalovirus. Complement-fixation, hemagglutination-inhibition, and/or serum-neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred during March and showed that infections with cytomegalovirus and respiratory syncytial virus also occurred during late March and April. The patient's persistent fever, for which other causes could not be found, may have been associated with one or more of these infections. Upper respiratory symptoms and lung involvement were not found during this period. Mild liver dysfunction during this time could not be clearly related to adenovirus infection because of the presence of multiple other causes. The adenovirus may have been latent in the donor kidney and become active in the new host as a consequence of immunological impairment. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group IA. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1.304 g/ml for the group CF antigen (hexon), 1.295 g/ml for the major soluble complete hemagglutinin (dodecon), and 1.206 g/ml for the minor soluble complete hemagglutinin (tentatively, fiber dimer). The virus does not cross-react in reciprocal hemagglutination-inhibition and serum-neutralization tests with antisera to adenovirus types 1 to 33. We propose this virus as candidate adenovirus type 34 (Compton)."} {"id": "PMID:170314", "title": "Radioimmunoassay for detection of antibodies to Epstein-Barr virus in human infectious mononucleosis serum specimens.", "content": "A rapid microradioimmunoassay (RIA) technique was adapted for quantitatively measuring antibody titers to antigens occurring in Epstein-Barr virus (EBV)-infected lymphoid cells. In these experiments two EBV-infected cell lines, HR1K and EB-3, were used as antigen-positive cells and Molt-4 was used as the negative control cells. The antibody titers of sera from suspected infectious mononucleosis patients were compared by RIA and indirect fluorescent antibody (IFA) methods. As determined by each of the methods, 14 of 19 sera had positive antibody titers and the remainder of the sera had negative antibody titers. Thus, the two methods agreed completely in differentiating sera with antibodies to EBV antigens. To further evaluate the antibody specificity of the RIA, the antibody titers of paired sera, pre- or early infection and postinfection, from five confirmed infectious mononucleosis patients were determined by RIA and IFA. Seroconversion was demonstrated by both RIA and IFA for each of the patients. Thus, the sensitivity and specificity of the two procedures are about the same.", "contents": "Radioimmunoassay for detection of antibodies to Epstein-Barr virus in human infectious mononucleosis serum specimens. A rapid microradioimmunoassay (RIA) technique was adapted for quantitatively measuring antibody titers to antigens occurring in Epstein-Barr virus (EBV)-infected lymphoid cells. In these experiments two EBV-infected cell lines, HR1K and EB-3, were used as antigen-positive cells and Molt-4 was used as the negative control cells. The antibody titers of sera from suspected infectious mononucleosis patients were compared by RIA and indirect fluorescent antibody (IFA) methods. As determined by each of the methods, 14 of 19 sera had positive antibody titers and the remainder of the sera had negative antibody titers. Thus, the two methods agreed completely in differentiating sera with antibodies to EBV antigens. To further evaluate the antibody specificity of the RIA, the antibody titers of paired sera, pre- or early infection and postinfection, from five confirmed infectious mononucleosis patients were determined by RIA and IFA. Seroconversion was demonstrated by both RIA and IFA for each of the patients. Thus, the sensitivity and specificity of the two procedures are about the same."} {"id": "PMID:170315", "title": "Physicochemical and serological characteristics of respiratory virus fluorescein-isothiocyanate conjugates for fluorescent-antibody diagnosis.", "content": "Fluorescein-isothiocyanate (FITC) conjugates were prepared by improved methods from standard reference antisera to influenza A and B, mumps, parainfluenza 1, 2, 3, and 4, herpesvirus, respiratory syncytial virus, and adenovirus hexon. The antisera, prepared in a variety of animals, were fractionated three times with selected optimal concentrations of ammonium sulfate and yielded gamma globulins of adequate purity for conjugation with FITC. Conjugates containing optimal fluorescein-to-protein ratios of between 5 and 10 were produced in 2 h by dialysis labeling. Serological titers of each antiserum and conjugate were determined by complement fixation, hemagglutination-inhibition, serum neutralization, and indirect hemagglutination tests where appropriate. When corrected for dilution, the serological titers of the FITC conjugates were identical to those of the starting antisera. The fluorescent-antibody staining titers correlated well with one of the serological parameters of the original serum. The conjugates stained homologous antigens specifically and were free of nonspecific staining at the working dilution. Undesired staining of host cells which was a problem with some of the conjugates produced from sera containing cellular antibodies was removed by absorption with packed cells. These physicochemical and serological findings were then used as a guide in preparing high quality reagents for fluorescent-antibody identification of respiratory viruses.", "contents": "Physicochemical and serological characteristics of respiratory virus fluorescein-isothiocyanate conjugates for fluorescent-antibody diagnosis. Fluorescein-isothiocyanate (FITC) conjugates were prepared by improved methods from standard reference antisera to influenza A and B, mumps, parainfluenza 1, 2, 3, and 4, herpesvirus, respiratory syncytial virus, and adenovirus hexon. The antisera, prepared in a variety of animals, were fractionated three times with selected optimal concentrations of ammonium sulfate and yielded gamma globulins of adequate purity for conjugation with FITC. Conjugates containing optimal fluorescein-to-protein ratios of between 5 and 10 were produced in 2 h by dialysis labeling. Serological titers of each antiserum and conjugate were determined by complement fixation, hemagglutination-inhibition, serum neutralization, and indirect hemagglutination tests where appropriate. When corrected for dilution, the serological titers of the FITC conjugates were identical to those of the starting antisera. The fluorescent-antibody staining titers correlated well with one of the serological parameters of the original serum. The conjugates stained homologous antigens specifically and were free of nonspecific staining at the working dilution. Undesired staining of host cells which was a problem with some of the conjugates produced from sera containing cellular antibodies was removed by absorption with packed cells. These physicochemical and serological findings were then used as a guide in preparing high quality reagents for fluorescent-antibody identification of respiratory viruses."} {"id": "PMID:170316", "title": "Design and construction of an apparatus for the growth of micro cell cultures on standard glass microscope slides and its application for screening large numbers of sera by the indirect fluorescent antibody technique.", "content": "A simple stainless-steel apparatus was designed to contain standard microscope slides on which were grown micro cell cultures in the form of 16 individual monolayers per slide. The application of this apparatus for the screening of serum samples by fluorescent antibody techniques is described.", "contents": "Design and construction of an apparatus for the growth of micro cell cultures on standard glass microscope slides and its application for screening large numbers of sera by the indirect fluorescent antibody technique. A simple stainless-steel apparatus was designed to contain standard microscope slides on which were grown micro cell cultures in the form of 16 individual monolayers per slide. The application of this apparatus for the screening of serum samples by fluorescent antibody techniques is described."} {"id": "PMID:170317", "title": "Measurement of parainfluenza-3 virus antibody by the single radial hemolysis technique.", "content": "A single radial hemolysis assay for parainfluenza-3 virus antibody is described as a simple, sensitive, accurate, and precise alternative to hemagglutination inhibition and serum neutralization tests. A highly significant correlation exists between single radial hemolysis zone areas and hemagglutination inhibition titers of both serum and nasal secretion samples. Antibody conversions equivalent to as little as a twofold rise in hemagglutination inhibition titer are readily and reliably detected in sera and nasal secretions. Single radial hemolysis and hemagglutination inhibition activity was demonstrable in the immunoglobulin G fraction of a hyperimmune parainfluenza-3 virus antiserum.", "contents": "Measurement of parainfluenza-3 virus antibody by the single radial hemolysis technique. A single radial hemolysis assay for parainfluenza-3 virus antibody is described as a simple, sensitive, accurate, and precise alternative to hemagglutination inhibition and serum neutralization tests. A highly significant correlation exists between single radial hemolysis zone areas and hemagglutination inhibition titers of both serum and nasal secretion samples. Antibody conversions equivalent to as little as a twofold rise in hemagglutination inhibition titer are readily and reliably detected in sera and nasal secretions. Single radial hemolysis and hemagglutination inhibition activity was demonstrable in the immunoglobulin G fraction of a hyperimmune parainfluenza-3 virus antiserum."} {"id": "PMID:170318", "title": "Dispersion and cultivation of renal cells after short-term storage of kidneys.", "content": "A new method for the preparation of cell suspensions from human newborn kidneys is described. It involves the use of a mixture of trypsin-ethylenediaminetetraacetic acid and collagenase. The cell yields obtained after tissue dispersion by this method were significantly greater than those obtained after dispersion with either trypsin or ethylenediaminetetraacetic acid alone or in combination. When kidneys were removed 12 h or more postmortem from refrigerated cadavers, higher cell yields were obtained from renal tissue stored overnight at 4 to 6 C in CMRL ATM (Healy and Parker, 1966), as compared to cell yields obtained from kidneys processed immediately upon removal. This observation was confirmed by controlled experiments performed with rabbit kidneys.", "contents": "Dispersion and cultivation of renal cells after short-term storage of kidneys. A new method for the preparation of cell suspensions from human newborn kidneys is described. It involves the use of a mixture of trypsin-ethylenediaminetetraacetic acid and collagenase. The cell yields obtained after tissue dispersion by this method were significantly greater than those obtained after dispersion with either trypsin or ethylenediaminetetraacetic acid alone or in combination. When kidneys were removed 12 h or more postmortem from refrigerated cadavers, higher cell yields were obtained from renal tissue stored overnight at 4 to 6 C in CMRL ATM (Healy and Parker, 1966), as compared to cell yields obtained from kidneys processed immediately upon removal. This observation was confirmed by controlled experiments performed with rabbit kidneys."} {"id": "PMID:170319", "title": "Optimal cooling and warming rates in the preservation of herpes simplex virus (type 2).", "content": "Fast rates of cooling and warming were optimal for survival of herpes simplex virus, type 2. Under these conditions cryoprotectants were not necessary for virus preservation.", "contents": "Optimal cooling and warming rates in the preservation of herpes simplex virus (type 2). Fast rates of cooling and warming were optimal for survival of herpes simplex virus, type 2. Under these conditions cryoprotectants were not necessary for virus preservation."} {"id": "PMID:170320", "title": "Lobular carcinoma of the breast: a special variant of mucin-secreting carcinoma.", "content": "There is currently much speculation over the precise nature of lobular carcinoma in-situ of the breast and its significance. Histochemical study shows that it is rich in sialomucin. This has a characteristic intracellular distribution which distinghishes lobular carcinoma in-situ from cancerization of lobules. The same histochemical features are seen in the infiltrative phase of the tumour. These findings invalidate the concept that it is a myoepithelial-cell tumour. Practical applications of the distinctive pattern of mucin secretion are discussed.", "contents": "Lobular carcinoma of the breast: a special variant of mucin-secreting carcinoma. There is currently much speculation over the precise nature of lobular carcinoma in-situ of the breast and its significance. Histochemical study shows that it is rich in sialomucin. This has a characteristic intracellular distribution which distinghishes lobular carcinoma in-situ from cancerization of lobules. The same histochemical features are seen in the infiltrative phase of the tumour. These findings invalidate the concept that it is a myoepithelial-cell tumour. Practical applications of the distinctive pattern of mucin secretion are discussed."} {"id": "PMID:170331", "title": "Diaminobenzidine reactivity of mitochondria and peroxisomes in Tetrahymena and in wild-type and cytochrome oxidase-deficient Paramecium.", "content": "Reactivity of mitochondria and peroxisomes to diaminobenzidine was investigated in Tetrahymena pyriformis and in wild-type and cytochrome oxidase-deficient Paramecium aurelia. Wild-type and cytochrome oxidase-deficient Paramecium gave positive mitochondrial reactions in the absence of added H2O2, and the deposits were enhanced by the addition of H2O2, whereas Tetrahymena gave positive mitochondrial reactions only upon addition of H2O2. These results are discussed in the light of the current ideas concerning the mechanism of staining by diaminobenzidine. Peroxisome-like organelles which react positively to diaminobenzidine, the reaction being partially inhibited by aminotriazole, were identified in both protozoa.", "contents": "Diaminobenzidine reactivity of mitochondria and peroxisomes in Tetrahymena and in wild-type and cytochrome oxidase-deficient Paramecium. Reactivity of mitochondria and peroxisomes to diaminobenzidine was investigated in Tetrahymena pyriformis and in wild-type and cytochrome oxidase-deficient Paramecium aurelia. Wild-type and cytochrome oxidase-deficient Paramecium gave positive mitochondrial reactions in the absence of added H2O2, and the deposits were enhanced by the addition of H2O2, whereas Tetrahymena gave positive mitochondrial reactions only upon addition of H2O2. These results are discussed in the light of the current ideas concerning the mechanism of staining by diaminobenzidine. Peroxisome-like organelles which react positively to diaminobenzidine, the reaction being partially inhibited by aminotriazole, were identified in both protozoa."} {"id": "PMID:170332", "title": "An investigation of the possible transmission of Rhinovirus colds through indirect contact.", "content": "Rhinovirus was recovered from the fingers of 16 of 38 volunteers and others, who were swabbed during the acute stages of their colds. Very low titres of virus were also recovered from 6 of 40 objects recently handled by infected volunteers, but not from the fingers of 18 non-infected subjects whose flat-mates were shedding virus. When rhinovirus from nasal secretions was dried on skin or other surfaces during laboratory experiments, approximately 40-99% of infectivity was lost. Virus could be transferred from surface to surface by rubbing, the transfer being more efficient if it was carried out while the inoculum was still damp. Volunteers could infect themselves if a moderately heavy dose (88 TCD50) of virus was inoculated on the finger and then rubbed into the conjunctiva or nostril, especially if the inoculum was still damp. From estimates of virus titres in nasal washings and on fingers, and of amounts transferred by rubbing, it was concluded that apread of colds is unlikely to occur via objects contaminated by the hands of the virus-shedder, but that a receipient might pick up enough virus on his fingers by direct contact with heavily infected skin or secretions to constitute a risk of self-inoculation via the conjunctiva or nostril.", "contents": "An investigation of the possible transmission of Rhinovirus colds through indirect contact. Rhinovirus was recovered from the fingers of 16 of 38 volunteers and others, who were swabbed during the acute stages of their colds. Very low titres of virus were also recovered from 6 of 40 objects recently handled by infected volunteers, but not from the fingers of 18 non-infected subjects whose flat-mates were shedding virus. When rhinovirus from nasal secretions was dried on skin or other surfaces during laboratory experiments, approximately 40-99% of infectivity was lost. Virus could be transferred from surface to surface by rubbing, the transfer being more efficient if it was carried out while the inoculum was still damp. Volunteers could infect themselves if a moderately heavy dose (88 TCD50) of virus was inoculated on the finger and then rubbed into the conjunctiva or nostril, especially if the inoculum was still damp. From estimates of virus titres in nasal washings and on fingers, and of amounts transferred by rubbing, it was concluded that apread of colds is unlikely to occur via objects contaminated by the hands of the virus-shedder, but that a receipient might pick up enough virus on his fingers by direct contact with heavily infected skin or secretions to constitute a risk of self-inoculation via the conjunctiva or nostril."} {"id": "PMID:170333", "title": "Serological survey of parainfluenza and parotitis in the population of Czechoslovakia.", "content": "A serological survey was carried out to determine the prevalence and age distribution of HI antibodies against M. parainfluenzae type 1, 2, 3 and 4A and against M. parotitis in the population on from 7 regions of the Czech Socialist Republic. While the distribution of antibodies to M. parainfluenzae is similar in all regions under study, considerable regional differences have been found in the occurence of antibodies against parotitis virus.", "contents": "Serological survey of parainfluenza and parotitis in the population of Czechoslovakia. A serological survey was carried out to determine the prevalence and age distribution of HI antibodies against M. parainfluenzae type 1, 2, 3 and 4A and against M. parotitis in the population on from 7 regions of the Czech Socialist Republic. While the distribution of antibodies to M. parainfluenzae is similar in all regions under study, considerable regional differences have been found in the occurence of antibodies against parotitis virus."} {"id": "PMID:170334", "title": "Two novel stimuli of cyclic adenosine 3',5'-monophosphate (cAMP) in human lymphocytes.", "content": "Polystyrene latex particles (PLP) and zymosan particles (ZP), two commonly employed phagocytic stimuli, were noted to bind to purified human peripheral blood lymphocytes. This interaction was not accompained by ingestion but did lead to a marked increase in intracellular cyclic AMP. The cAMP response to PLP was proportional to the particle cell ratio which, in turn, correlated with the number of membrane-associated particles. After the addition of PLP to lymphocytes, the cAMP response occurred within 2 min, peaked between 4 and 15 min, and returned to baseline by 30 to 60 min. The cAMP response to ZP was similar in onset and duration to that seen with PLP but was less marked (2- to 4-fold vs 25- to 50-fold) and more variable in magnitude. This is probably a reflection of the smaller number of cells interacting with ZP. At high PLP to cell ratios almost all of the lymphocytes bound PLP but only 10 to 28% of the mixed lymphocyte population bound ZP. Two lines of evidence established conclusively that the cAMP response was taking place in the lymphocytes themselves rather than in contaminating cells. 1) When lymphocytes were purified additionally by filtration through a nylon wool column (99 to 100% lymphocytes), they were found to undergo a similar cAMP response to PLP. Since the nylon filtration procedure also removes almost all of the B cells, this further indicates that T cells are capable of undergoing the response. 2) Immunofluorescence studies with anti-cAMP antibody revealed an increase in intralymphocytic cAMP which was primarily adjacent to the site of PLP or ZP attachment. The likely explanation of this data is that PLP and ZP perturb the lymphocyte surface leading to regional activation of membrane-bound adenylate cyclase and subsequent cAMP accumulation. Although the physiologic significance of these observations remains to be determined, the results: 1) provide histologic confirmation for the concept of cAMP compartmentablization, 2) clarify conflicting results regarding the localization of cAMP accumulation during the phagocytosis of PLP by mixed leukocyte populations, and 3) suggest that this experimental system may allow an analysis of the mechanism by which perturbations of the lymphocyte surface modulate cAMP.", "contents": "Two novel stimuli of cyclic adenosine 3',5'-monophosphate (cAMP) in human lymphocytes. Polystyrene latex particles (PLP) and zymosan particles (ZP), two commonly employed phagocytic stimuli, were noted to bind to purified human peripheral blood lymphocytes. This interaction was not accompained by ingestion but did lead to a marked increase in intracellular cyclic AMP. The cAMP response to PLP was proportional to the particle cell ratio which, in turn, correlated with the number of membrane-associated particles. After the addition of PLP to lymphocytes, the cAMP response occurred within 2 min, peaked between 4 and 15 min, and returned to baseline by 30 to 60 min. The cAMP response to ZP was similar in onset and duration to that seen with PLP but was less marked (2- to 4-fold vs 25- to 50-fold) and more variable in magnitude. This is probably a reflection of the smaller number of cells interacting with ZP. At high PLP to cell ratios almost all of the lymphocytes bound PLP but only 10 to 28% of the mixed lymphocyte population bound ZP. Two lines of evidence established conclusively that the cAMP response was taking place in the lymphocytes themselves rather than in contaminating cells. 1) When lymphocytes were purified additionally by filtration through a nylon wool column (99 to 100% lymphocytes), they were found to undergo a similar cAMP response to PLP. Since the nylon filtration procedure also removes almost all of the B cells, this further indicates that T cells are capable of undergoing the response. 2) Immunofluorescence studies with anti-cAMP antibody revealed an increase in intralymphocytic cAMP which was primarily adjacent to the site of PLP or ZP attachment. The likely explanation of this data is that PLP and ZP perturb the lymphocyte surface leading to regional activation of membrane-bound adenylate cyclase and subsequent cAMP accumulation. Although the physiologic significance of these observations remains to be determined, the results: 1) provide histologic confirmation for the concept of cAMP compartmentablization, 2) clarify conflicting results regarding the localization of cAMP accumulation during the phagocytosis of PLP by mixed leukocyte populations, and 3) suggest that this experimental system may allow an analysis of the mechanism by which perturbations of the lymphocyte surface modulate cAMP."} {"id": "PMID:170335", "title": "The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. The inhibition of neutrophil movement and the elevation of cyclic AMP levels by catecholamines, prostaglandins, theophylline and cholera toxin.", "content": "Agents known to affect intracellular levels of cyclic AMP in many diverse systems have been tested for their effect on the chemotaxis induced by Escherichia coli culture filtrates, spontaneous motility and cyclic AMP levels of rabbit peritoneal neutrophils. Prostaglandin E1 and A1 but not prostaglandin F2alpha increased neutrophil cyclic AMP levels and, correspondingly, only the former two prostaglandins inhibited chemotaxis. Nevertheless, a quantitative relationship between prostaglandin stimulation of cyclic AMP and inhibition of chemotaxis could not be found. Epinephrine, isoproterenol, and, to a much lesser extent, norepinephrine increased neutrophil cyclic AMP through beta adrenergic stimulation. Only epinephrine and isoproterenol inhibited chemotaxis, but the inhibition was variable and not related to the ability of these catecholamines to increase intracellular cyclic AMP. Cholera toxin increased neutrophil cyclic AMP after a 30-min lag period which paralled its inhibitory effect on chemotaxis and spontaneous motility. However, the effect on chemotaxis require 50 ng/ml of toxin whereas the effect on cyclic AMP was manifested at 2 ng/ml of toxin. Prior to 30-min preincubation there was no effect of even 1250 ng/ml of toxin on either cyclic AMP or chemotaxis. Choleragenoid prevented the effects of toxin on both cyclic AMP and chemotaxis. The bacterial chemotactic factor obtained from E. coli culture filtrates did not effect a measurable change in levels of neutrophil cyclic AMP. The data indicate that even though cyclic AMP is not, in the main sequence of events, triggering the chemotactic response, increases in neutrophil cyclic AMP may modulate the movement and thus the chemotactic responsiveness of the neutrophil.", "contents": "The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. The inhibition of neutrophil movement and the elevation of cyclic AMP levels by catecholamines, prostaglandins, theophylline and cholera toxin. Agents known to affect intracellular levels of cyclic AMP in many diverse systems have been tested for their effect on the chemotaxis induced by Escherichia coli culture filtrates, spontaneous motility and cyclic AMP levels of rabbit peritoneal neutrophils. Prostaglandin E1 and A1 but not prostaglandin F2alpha increased neutrophil cyclic AMP levels and, correspondingly, only the former two prostaglandins inhibited chemotaxis. Nevertheless, a quantitative relationship between prostaglandin stimulation of cyclic AMP and inhibition of chemotaxis could not be found. Epinephrine, isoproterenol, and, to a much lesser extent, norepinephrine increased neutrophil cyclic AMP through beta adrenergic stimulation. Only epinephrine and isoproterenol inhibited chemotaxis, but the inhibition was variable and not related to the ability of these catecholamines to increase intracellular cyclic AMP. Cholera toxin increased neutrophil cyclic AMP after a 30-min lag period which paralled its inhibitory effect on chemotaxis and spontaneous motility. However, the effect on chemotaxis require 50 ng/ml of toxin whereas the effect on cyclic AMP was manifested at 2 ng/ml of toxin. Prior to 30-min preincubation there was no effect of even 1250 ng/ml of toxin on either cyclic AMP or chemotaxis. Choleragenoid prevented the effects of toxin on both cyclic AMP and chemotaxis. The bacterial chemotactic factor obtained from E. coli culture filtrates did not effect a measurable change in levels of neutrophil cyclic AMP. The data indicate that even though cyclic AMP is not, in the main sequence of events, triggering the chemotactic response, increases in neutrophil cyclic AMP may modulate the movement and thus the chemotactic responsiveness of the neutrophil."} {"id": "PMID:170337", "title": "Studies on the adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes in the mouse. I. In vitro enhancement of antibody formation with normal spleen cells.", "content": "The adjuvant effect of Bordetella pertussis vaccine (PV) on the antibody response to sheep erythrocytes (SRBC) has been studied in vitro with the Mishell-Dutton immunization technique. The addition of PV to cultures of spleen cells obtained from normal non-immunized mice markedly enhanced the plaque-forming cell response to SRBC. The greatest enhancement was evident at 24 hr of culture. PV was also shown to enhance the antibody response of spleen cells that had been depleted of either T lymphocytes or adherent cells, presumably macrophages. In addition, it was found that PV, per se, released into the culture medium a soluble cell-free component(s) that contributed significantly to adjuvanticity. The results suggest that at least one of the ways that PV enhances the in vitro immune response to SRBC is by direct stimulation of precursors of antibody-forming cells.", "contents": "Studies on the adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes in the mouse. I. In vitro enhancement of antibody formation with normal spleen cells. The adjuvant effect of Bordetella pertussis vaccine (PV) on the antibody response to sheep erythrocytes (SRBC) has been studied in vitro with the Mishell-Dutton immunization technique. The addition of PV to cultures of spleen cells obtained from normal non-immunized mice markedly enhanced the plaque-forming cell response to SRBC. The greatest enhancement was evident at 24 hr of culture. PV was also shown to enhance the antibody response of spleen cells that had been depleted of either T lymphocytes or adherent cells, presumably macrophages. In addition, it was found that PV, per se, released into the culture medium a soluble cell-free component(s) that contributed significantly to adjuvanticity. The results suggest that at least one of the ways that PV enhances the in vitro immune response to SRBC is by direct stimulation of precursors of antibody-forming cells."} {"id": "PMID:170338", "title": "The requirement for macrophage-lymphocyte interaction in T lymphocyte proliferation induced by generation of aldehydes on cell membranes.", "content": "Guinea pig T lymphocyte proliferation induced by sodium periodate (NaIO4) or neuraminidase-galactose oxidase (NG) occurs when lymphocytes and macrophages are cultured together after treatment of either purified T lymphocytes or macrophages with these agents. Regardless of which cell initially bears the modified surface carbohydrate, lymphocyte proliferation requires the presence of viable homologous macrophages and fails to occur when they are replaced with fibroblasts, erythrocytes, L2C leukemia cells, thymocytes, PMN, line I hepatoma cells, or murine macrophages. Lymphocyte proliferation resulting from NaIO4 or NG treatment of lymphocytes is diminished when these cells are treated with proteolytic enzymes or aged in in vitro culture for 48 hr. By contrast, proteolytic enzyme treatment or in vitro aging has no effect on the ability of NaIO4 or NG-treated macrophages to induce lymphocyte proliferation. The requirement for macrophage-lymphocyte interaction in NaIO4 or NG-induced lymphocyte proliferation is indicative of a central role for the macrophage in the initiation of T lymphocyte proliferation.", "contents": "The requirement for macrophage-lymphocyte interaction in T lymphocyte proliferation induced by generation of aldehydes on cell membranes. Guinea pig T lymphocyte proliferation induced by sodium periodate (NaIO4) or neuraminidase-galactose oxidase (NG) occurs when lymphocytes and macrophages are cultured together after treatment of either purified T lymphocytes or macrophages with these agents. Regardless of which cell initially bears the modified surface carbohydrate, lymphocyte proliferation requires the presence of viable homologous macrophages and fails to occur when they are replaced with fibroblasts, erythrocytes, L2C leukemia cells, thymocytes, PMN, line I hepatoma cells, or murine macrophages. Lymphocyte proliferation resulting from NaIO4 or NG treatment of lymphocytes is diminished when these cells are treated with proteolytic enzymes or aged in in vitro culture for 48 hr. By contrast, proteolytic enzyme treatment or in vitro aging has no effect on the ability of NaIO4 or NG-treated macrophages to induce lymphocyte proliferation. The requirement for macrophage-lymphocyte interaction in NaIO4 or NG-induced lymphocyte proliferation is indicative of a central role for the macrophage in the initiation of T lymphocyte proliferation."} {"id": "PMID:170339", "title": "Immunosuppression by spleen cells from Moloney leukemia. Comparison of the suppressive effect on antibody response and on mitogen-induced response.", "content": "The inhibitory effect of cells from leukemic spleens on the immune functions of normal lymphocytes was studied. Suppressor cells were obtained as the nonadherent fraction (NA) from splenic tumors of mice infected with MuLV-Moloney. This fraction (NA MuLV- M) contained less than 10% membrane Ig-positive (Ig+) cells, 45 to 60% theta-positive cells (theta+) and 40 to 50% naught cells (theta-, Ig-). Similarly prepared fractions from normal control spleens (NAc) containing 75 to 90% theta+cells and less than 10% Ig+ and naught cells were utilized in control cultures. Addition of the NA MuLV- M cells into cultures (Marbrook system) of normal spleen cells with sheep red blood cells suppressed the specific antibody response determined by the number of hemolytic plaque forming cells (PFC). The PFC response was significantly suppressed at a suppressor cell to responder cell ratio of 1:100, and was completely abolished at a ratio of 1:10 or higher. The control NAc fraction showed some inhibitory effect only at high suppressor to responder ratios (1:2 or 1:1). In contrast, the suppressive effect of NAMuLV-M on mitogen-induced 3H-thymidine incorporation in normal B and T cells was much weaker. Very little, if any, suppression occurred at the ratio of 1:100 or 1:10, however, about 50% decrease in DNA synthesis was observed at the ratio 1:2 or 1:1. On the basis of this differential suppressive effect, it is suggested that leukemic spleen cells can suppress the function of immunocompetent cells by more than one mechanism.", "contents": "Immunosuppression by spleen cells from Moloney leukemia. Comparison of the suppressive effect on antibody response and on mitogen-induced response. The inhibitory effect of cells from leukemic spleens on the immune functions of normal lymphocytes was studied. Suppressor cells were obtained as the nonadherent fraction (NA) from splenic tumors of mice infected with MuLV-Moloney. This fraction (NA MuLV- M) contained less than 10% membrane Ig-positive (Ig+) cells, 45 to 60% theta-positive cells (theta+) and 40 to 50% naught cells (theta-, Ig-). Similarly prepared fractions from normal control spleens (NAc) containing 75 to 90% theta+cells and less than 10% Ig+ and naught cells were utilized in control cultures. Addition of the NA MuLV- M cells into cultures (Marbrook system) of normal spleen cells with sheep red blood cells suppressed the specific antibody response determined by the number of hemolytic plaque forming cells (PFC). The PFC response was significantly suppressed at a suppressor cell to responder cell ratio of 1:100, and was completely abolished at a ratio of 1:10 or higher. The control NAc fraction showed some inhibitory effect only at high suppressor to responder ratios (1:2 or 1:1). In contrast, the suppressive effect of NAMuLV-M on mitogen-induced 3H-thymidine incorporation in normal B and T cells was much weaker. Very little, if any, suppression occurred at the ratio of 1:100 or 1:10, however, about 50% decrease in DNA synthesis was observed at the ratio 1:2 or 1:1. On the basis of this differential suppressive effect, it is suggested that leukemic spleen cells can suppress the function of immunocompetent cells by more than one mechanism."} {"id": "PMID:170340", "title": "Complete local tumor regression with antibody to fibrin Fragment E.", "content": "Rabbit antibody to fibrin fragment E (FFE) was used in an immunotherapy model for the treatment of the line-10 ascites variant of a diethylnitrosamine-induced hepatoma in strain 2 guinea pigs. When 0.75 or 1.0 mg of an IgG preparation containing anti-FFE antibody was injected s.c. 6 and 16 days after the injection of a uniformly lethal dose of line-10 tumor cells, complete regression of the i.d. growing tumor was observed in all 18 strain 2 guinea pigs treated. Thus, this therapy appears to be more effective than any BCG or other immunotherapeutic regimen thus far reported for this tumor. No significant anti-tumor effect was noted when normal rabbit IgG or smaller doses (0.25 or 0.50 mg) of the anti-FFE IgG preparation were used. The injection sites exhibited an inflammatory response for 7 to 10 days characterized by erythema and hemorrhage. Since all animals were treated after the metastatic progression of the tumor is known to frequently occur, the long-term tumor-free survival of these animals as well as their resistance to subsequent tumor challenge indicate that the anti-FFE antibody therapy led to systemic tumor immunity.", "contents": "Complete local tumor regression with antibody to fibrin Fragment E. Rabbit antibody to fibrin fragment E (FFE) was used in an immunotherapy model for the treatment of the line-10 ascites variant of a diethylnitrosamine-induced hepatoma in strain 2 guinea pigs. When 0.75 or 1.0 mg of an IgG preparation containing anti-FFE antibody was injected s.c. 6 and 16 days after the injection of a uniformly lethal dose of line-10 tumor cells, complete regression of the i.d. growing tumor was observed in all 18 strain 2 guinea pigs treated. Thus, this therapy appears to be more effective than any BCG or other immunotherapeutic regimen thus far reported for this tumor. No significant anti-tumor effect was noted when normal rabbit IgG or smaller doses (0.25 or 0.50 mg) of the anti-FFE IgG preparation were used. The injection sites exhibited an inflammatory response for 7 to 10 days characterized by erythema and hemorrhage. Since all animals were treated after the metastatic progression of the tumor is known to frequently occur, the long-term tumor-free survival of these animals as well as their resistance to subsequent tumor challenge indicate that the anti-FFE antibody therapy led to systemic tumor immunity."} {"id": "PMID:170341", "title": "Production of interferon by immune lymphocytes exposed to herpes simplex virus-antibody complexes.", "content": "Splenic leukocytes from rabbits immunized with herpes simplex virus (HSV) incorporated significant amounts of 3H-TdR and produced interferon after in vitro incubation with HSV antigens. In contrast, splenic leukocytes from nonimmune rabbits did not incorporate 3H-TdR or produce interferon when incubated with HSV antigens. Antigen-antibody complexes consisting of HSV antigens and anti-HSV antibody also were capable of stimulating immune leukocytes to incorporate 3H-TdR and to produce interferon.", "contents": "Production of interferon by immune lymphocytes exposed to herpes simplex virus-antibody complexes. Splenic leukocytes from rabbits immunized with herpes simplex virus (HSV) incorporated significant amounts of 3H-TdR and produced interferon after in vitro incubation with HSV antigens. In contrast, splenic leukocytes from nonimmune rabbits did not incorporate 3H-TdR or produce interferon when incubated with HSV antigens. Antigen-antibody complexes consisting of HSV antigens and anti-HSV antibody also were capable of stimulating immune leukocytes to incorporate 3H-TdR and to produce interferon."} {"id": "PMID:170342", "title": "Anomalous reactions of mouse alloantisera with cultured tumor cells. II. Cytotoxicity is caused by antibodies to leukemia viruses.", "content": "Certain alloantisera prepared in mice against H-2 region membrane antigens were found to be unexpectedly cytotoxic for murine sarcoma and leukemia cells in culture. This anomalous cytotoxicity was shown to be the result of antibody in these alloantisera directed against the p15 and gp70 envelope proteins of Mu LV which were present on the surface of the tumor target cells. Sera from aged unimmunized mice of strains used for the preparation of alloantisera also contained antibodies against MuLV protein p15 and gp70 that were cytotoxic for sarcoma and leukemia cells, which indicates that these antibodies occurred naturally in mice. These results independently confirm earlier findings of the widespread occurrence in mouse serum of antibodies reactive with MuLV. The presence of antibody against MuLV in mouse serum which can cause cytotoxic reactions with tumor cells points to the fact that particular caution should be used during the typing of murine sarcomas or leukemias for cell surface antigens, since mouse antisera may yield cytotoxicity (or other serologic reactions) based on anti-MuLV specificities, rather than on anticipated antigens.", "contents": "Anomalous reactions of mouse alloantisera with cultured tumor cells. II. Cytotoxicity is caused by antibodies to leukemia viruses. Certain alloantisera prepared in mice against H-2 region membrane antigens were found to be unexpectedly cytotoxic for murine sarcoma and leukemia cells in culture. This anomalous cytotoxicity was shown to be the result of antibody in these alloantisera directed against the p15 and gp70 envelope proteins of Mu LV which were present on the surface of the tumor target cells. Sera from aged unimmunized mice of strains used for the preparation of alloantisera also contained antibodies against MuLV protein p15 and gp70 that were cytotoxic for sarcoma and leukemia cells, which indicates that these antibodies occurred naturally in mice. These results independently confirm earlier findings of the widespread occurrence in mouse serum of antibodies reactive with MuLV. The presence of antibody against MuLV in mouse serum which can cause cytotoxic reactions with tumor cells points to the fact that particular caution should be used during the typing of murine sarcomas or leukemias for cell surface antigens, since mouse antisera may yield cytotoxicity (or other serologic reactions) based on anti-MuLV specificities, rather than on anticipated antigens."} {"id": "PMID:170343", "title": "Cell-mediated immunity to Friend virus-induced leukemia. I. Modification of 125IUdR release cytotoxicity assay for use with suspension target cells.", "content": "Cell-mediated cytotoxic reactivity of C57BL/6 mice against syngeneic FBL-3 cells, a Friend virus-induced leukemia, was measured by the 125IUdR release assay with tumor target cells in suspension. The tests could be performed either with Linbro tissue culture plates(16-mm wells) or with Microtest II plates (6-mm wells). The former could only be harvested manually; the latter could be harvested mechanically by an automatic harvesting apparatus which permitted larger scale tests. With either plate, it was found that careful preparation of the target cells and of the attacker cells has important effects on the results obtained. When performed under optimal test conditions, the 125IUdR assay can be used as a very simple, objective, and reproducible assay for testing cell-mediated cytotoxicity.", "contents": "Cell-mediated immunity to Friend virus-induced leukemia. I. Modification of 125IUdR release cytotoxicity assay for use with suspension target cells. Cell-mediated cytotoxic reactivity of C57BL/6 mice against syngeneic FBL-3 cells, a Friend virus-induced leukemia, was measured by the 125IUdR release assay with tumor target cells in suspension. The tests could be performed either with Linbro tissue culture plates(16-mm wells) or with Microtest II plates (6-mm wells). The former could only be harvested manually; the latter could be harvested mechanically by an automatic harvesting apparatus which permitted larger scale tests. With either plate, it was found that careful preparation of the target cells and of the attacker cells has important effects on the results obtained. When performed under optimal test conditions, the 125IUdR assay can be used as a very simple, objective, and reproducible assay for testing cell-mediated cytotoxicity."} {"id": "PMID:170344", "title": "The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes.", "content": "When bone marrow and spleen cells of 4 week-old mice are fractionated on a discontinuous BSA gradient, a small fraction of Ia- cells is obtained which can be induced in vitro to express the Ia alloantigen within 2 hr. This is in precise parallel to the prothymocyte induction system of Komuro and Boyse. Ia specificity is ascertained by the use of two reciprocal antisera, A.TH anti-A.TL (anti-Iak) and A.TL anti-A.TH (anti-Ias), which yield the expected reaction pattern on induced bone marrow cells of (B6 X A)F1 (Iak) and SJL/J (Ias) mice. Induction can be effected by a number of agents, such as catecholamines, prostaglandin PGE1, cAMP, bacterial endotoxin, lipid A, ubiquitin, and thymopoietin. The last requires a 100-fold higher concentration for Ia+ induction as compared to prothymocyte induction, thus implying a lower affinity for the B cell receptor than for the thymocyte receptor. Ia- to Ia+ conversion involves cells different from prothymocytes, as indicated by: 1) the specific cytolytic effect of our anti-Ia sera which were shown to be free of activity against thymocytes; 2) an additive cytolytic effect of anti-Ia and anti-Thy-1 sera; and 3) the fact that the Ia inducible cells are sensitive to pretreatment with anti-immunoglobulin and C. This finding that Ia- precursor cells are already Ig+ is of interest for the B cell ontogeny, as it implies that Ig expression precedes Ia expression.", "contents": "The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes. When bone marrow and spleen cells of 4 week-old mice are fractionated on a discontinuous BSA gradient, a small fraction of Ia- cells is obtained which can be induced in vitro to express the Ia alloantigen within 2 hr. This is in precise parallel to the prothymocyte induction system of Komuro and Boyse. Ia specificity is ascertained by the use of two reciprocal antisera, A.TH anti-A.TL (anti-Iak) and A.TL anti-A.TH (anti-Ias), which yield the expected reaction pattern on induced bone marrow cells of (B6 X A)F1 (Iak) and SJL/J (Ias) mice. Induction can be effected by a number of agents, such as catecholamines, prostaglandin PGE1, cAMP, bacterial endotoxin, lipid A, ubiquitin, and thymopoietin. The last requires a 100-fold higher concentration for Ia+ induction as compared to prothymocyte induction, thus implying a lower affinity for the B cell receptor than for the thymocyte receptor. Ia- to Ia+ conversion involves cells different from prothymocytes, as indicated by: 1) the specific cytolytic effect of our anti-Ia sera which were shown to be free of activity against thymocytes; 2) an additive cytolytic effect of anti-Ia and anti-Thy-1 sera; and 3) the fact that the Ia inducible cells are sensitive to pretreatment with anti-immunoglobulin and C. This finding that Ia- precursor cells are already Ig+ is of interest for the B cell ontogeny, as it implies that Ig expression precedes Ia expression."} {"id": "PMID:170345", "title": "Reduced epidermal cyclic AMP accumulation following prostaglandin stimulation: Its possible role in the pathophysiology of psoriasis.", "content": "Since prostaglandins are known to be one of the modulators of cyclic AMP, a study of the role of prostaglandins and their relation to the regulation of the nucleotide in psoriasis was initiated. Guinea-pig epidermal preparations were incubated with prostaglandins (PGs) in the presence of theophylline. PGE1 increased cyclic AMP levels 3.5-fold whereas a 2-fold increase was seen with PGE2 and PGA1. The increase in cyclic AMP accumulation was linear with increasing concentration of PGE1, from 10(-11) to 10(-5) M. PGE1 significantly increased cyclic AMP in psoriatic epidermis in vitro; however, the stimulation of cyclic AMP accumulation was significantly less in involved epidermis as compared with uninvolved tissue. The specificity of this stimulation, its occurrence at physiologic levels, and the decreased responsiveness of the cyclic AMP system in psoriatic epidermis to PGE1 stimulation suggest that the altered response of epidermis to PGs may be one of the factors in the pathophysiology of psoriasis.", "contents": "Reduced epidermal cyclic AMP accumulation following prostaglandin stimulation: Its possible role in the pathophysiology of psoriasis. Since prostaglandins are known to be one of the modulators of cyclic AMP, a study of the role of prostaglandins and their relation to the regulation of the nucleotide in psoriasis was initiated. Guinea-pig epidermal preparations were incubated with prostaglandins (PGs) in the presence of theophylline. PGE1 increased cyclic AMP levels 3.5-fold whereas a 2-fold increase was seen with PGE2 and PGA1. The increase in cyclic AMP accumulation was linear with increasing concentration of PGE1, from 10(-11) to 10(-5) M. PGE1 significantly increased cyclic AMP in psoriatic epidermis in vitro; however, the stimulation of cyclic AMP accumulation was significantly less in involved epidermis as compared with uninvolved tissue. The specificity of this stimulation, its occurrence at physiologic levels, and the decreased responsiveness of the cyclic AMP system in psoriatic epidermis to PGE1 stimulation suggest that the altered response of epidermis to PGs may be one of the factors in the pathophysiology of psoriasis."} {"id": "PMID:170347", "title": "The effect of chenodeoxycholic acid feeding on bile acid kinetics and fecal neutral steroid excretion in patients with hyperlipoproteinemia types II and IV.", "content": "The kinetics of 24-14C-cholic acid and 3H-chenodeoxycholic acid and the elimination of cholesterol as fecal neutral steroids were studied in 6 patients with Type II and 7 patients with Type IV lipoprotein pattern before and during the ingestion of 0.8 to 1.0 Gm. of chenodeoxycholic acid per day. During treatment, the pool size of chenodeoxycholic acid increased in all subjects (not studied in one Type IV patient). In Type II patients, this effect was associated with a decrease of the cholic acid pool size from 868 +/- 141 to 213 +/- 51 mg. and of the cholic acid synthesis from 204 +/- 36 to 54 +/- 20 mg. per day. In the patients with hyperlopoproteinemia Type IV, the cholic acid pool size diminished in 6 of the 7 subjects all of whom showed a decrease in the cholic acid synthesis on the average from 607 +/- 155 to 202 +/- 44 mg. per day. It is suggested that the feedback control of cholic acid synthesis is less sensitive in the Type IV than in the Type II patients. Chenodeoxycholic acid feeding did not influence the fecal excretion of cholesterol, coprostanol, and coprostanone in a consistent way.", "contents": "The effect of chenodeoxycholic acid feeding on bile acid kinetics and fecal neutral steroid excretion in patients with hyperlipoproteinemia types II and IV. The kinetics of 24-14C-cholic acid and 3H-chenodeoxycholic acid and the elimination of cholesterol as fecal neutral steroids were studied in 6 patients with Type II and 7 patients with Type IV lipoprotein pattern before and during the ingestion of 0.8 to 1.0 Gm. of chenodeoxycholic acid per day. During treatment, the pool size of chenodeoxycholic acid increased in all subjects (not studied in one Type IV patient). In Type II patients, this effect was associated with a decrease of the cholic acid pool size from 868 +/- 141 to 213 +/- 51 mg. and of the cholic acid synthesis from 204 +/- 36 to 54 +/- 20 mg. per day. In the patients with hyperlopoproteinemia Type IV, the cholic acid pool size diminished in 6 of the 7 subjects all of whom showed a decrease in the cholic acid synthesis on the average from 607 +/- 155 to 202 +/- 44 mg. per day. It is suggested that the feedback control of cholic acid synthesis is less sensitive in the Type IV than in the Type II patients. Chenodeoxycholic acid feeding did not influence the fecal excretion of cholesterol, coprostanol, and coprostanone in a consistent way."} {"id": "PMID:170348", "title": "Lysosomal enzymes in normal and Chediak-Higashi blood leukocytes.", "content": "A method of blood granylocyte concentration and isolation of granules from both normal and neutropenic Chediak-Higashi syndrome (CHS) patients is described. the intracellular distribution of activity for several hydrolases in CHS granulocytes differs from normal; significantly more activity is present in the cytoplasmic fraction and correspondingly less is granule-associated. Isolated CHS granules are not more sensitive to the labilizing agents vitamin A, progesterone, or etiocholanolone. Specific activities of myeloperoxidase and ss-glucuronidase in CHS granulocytes are lower than normal while alkaline phosphatase is elevated. Other lysosomal enzyme activities are normal. Lysosomal enzyme distribution and content are similar in CHS and normal mononuclear cells. The possible significance of these findings is discussed.", "contents": "Lysosomal enzymes in normal and Chediak-Higashi blood leukocytes. A method of blood granylocyte concentration and isolation of granules from both normal and neutropenic Chediak-Higashi syndrome (CHS) patients is described. the intracellular distribution of activity for several hydrolases in CHS granulocytes differs from normal; significantly more activity is present in the cytoplasmic fraction and correspondingly less is granule-associated. Isolated CHS granules are not more sensitive to the labilizing agents vitamin A, progesterone, or etiocholanolone. Specific activities of myeloperoxidase and ss-glucuronidase in CHS granulocytes are lower than normal while alkaline phosphatase is elevated. Other lysosomal enzyme activities are normal. Lysosomal enzyme distribution and content are similar in CHS and normal mononuclear cells. The possible significance of these findings is discussed."} {"id": "PMID:170349", "title": "Accumulation of sulfate-containing acid mucopolysaccharides in I-cell fibroblasts.", "content": "A rapid and sensitive papper electrophoretic assay for 35SO4-containing compounds was developed which allowed measurement of 35S-acid mucopolysaccharides synthesized by skin fibroblasts grown in the presence of inorganic 35S-sulfate. Fibroblasts from a skin explant of a patient with I-cell disease when grown in culture accumulated abnormal amounts of 35S-acid mucopolysaccharides and other, as yet unidentified, 35S-labeled compounds. Approximately 75% of the 35S-compounds accumulated by I-cell fibroblasts were not metabolized and remained in the cells after transfer to nonlabeled medium. I-cell fibroblasts differ from fibroblasts derived from classical mucopolysaccharidoses such as Hurler's and Hunter's syndromes in the amount and types of 35S-labeled acid mucopolysaccharides accumulated. I-cell fibroblasts accumulated chondroitin 4- and 6-sulfates (16 per cent), dermatan sulfate (32 per cent), heparan sulfate (32 per cent), and other unidentified 35S-compounds. The unidentified fraction was not hydrolyzed by microbial chondroitinase or heparinase. Attempts to correct the defect in I-cell fibroblasts by growth in the presence of extracts of normal cells resulted in release of only 10 per cent of the accumulated mucopolysaccharides. Under the same conditions, Hurler and Hunter fibroblasts lost over 90 per cent of accumulated mucopolysaccharides.", "contents": "Accumulation of sulfate-containing acid mucopolysaccharides in I-cell fibroblasts. A rapid and sensitive papper electrophoretic assay for 35SO4-containing compounds was developed which allowed measurement of 35S-acid mucopolysaccharides synthesized by skin fibroblasts grown in the presence of inorganic 35S-sulfate. Fibroblasts from a skin explant of a patient with I-cell disease when grown in culture accumulated abnormal amounts of 35S-acid mucopolysaccharides and other, as yet unidentified, 35S-labeled compounds. Approximately 75% of the 35S-compounds accumulated by I-cell fibroblasts were not metabolized and remained in the cells after transfer to nonlabeled medium. I-cell fibroblasts differ from fibroblasts derived from classical mucopolysaccharidoses such as Hurler's and Hunter's syndromes in the amount and types of 35S-labeled acid mucopolysaccharides accumulated. I-cell fibroblasts accumulated chondroitin 4- and 6-sulfates (16 per cent), dermatan sulfate (32 per cent), heparan sulfate (32 per cent), and other unidentified 35S-compounds. The unidentified fraction was not hydrolyzed by microbial chondroitinase or heparinase. Attempts to correct the defect in I-cell fibroblasts by growth in the presence of extracts of normal cells resulted in release of only 10 per cent of the accumulated mucopolysaccharides. Under the same conditions, Hurler and Hunter fibroblasts lost over 90 per cent of accumulated mucopolysaccharides."} {"id": "PMID:170350", "title": "Interaction of rat plasma very low density lipoprotein with lipoprotein lipase-rich (postheparin) plasma.", "content": "Incubation of 125I-labeled very low density lipoprotein (VLDL) with lipoprotein lipase-rich (postheparin) plasma obtained from intact or supradiaphragmatic rats resulted in the transfer of more than 80% of apoprotein C from VLDL to high density lipoprotein (HDL), whereas apoprotein B was associated with lipoprotein of density less than 1.019 g/ml (intermediate lipoprotein). The transfer of 125I-labeled apoprotein C from VLDL to HDL increased with time and decreased in proportion to the amount of VLDL in the incubation system. A relationship was established between the content of triglycerides and apoprotein C in VLDL, whereas the amount of apoprotein C in VLDL was independent of that of other apoproteins, especially apoprotein B. The injection of heparin to rats preinjected with 125I-labeled VLDL caused apoprotein interconversions similar to those observed in vitro. The intermediate lipoprotein was relatively rich in apoprotein B, apoprotein VS-2, cholesterol, and phospholipids and poor in triglycerides and apoprotein C. The mean diameter of intermediate lipoprotein was 269 A (compared with 427 A, the mean Sf rate was 30.5 (compared with 115), and the mean weight was 7.0 X 10(6) daltons (compared with 23.1 X 10(6)). From these data it was possible to calculate the mass of lipids and apoproteins in single lipoprotein particles. The content of apoprotein B in both particles was virtually identical, 0.7 X 10(6) daltons. The relative amount of all other constituents in intermediate lipoprotein was lower than in VLDL: triglycerides, 22%; free cholesterol, 37%; esterified cholesterol, 68%; phospholipids, 41%; apoprotein C, 7%, and VS-2 apoprotein, 60%. The data indicate that (a) one and only one intermediate lipoprotein is formed from each VLDL particle, and (b) during the formation of the intermediate lipoprotein all lipid and apoprotein components other than apoprotein B leave the density range of VLDL to a varying degree. Whether these same changes occur during the clearance of VLDL in vivo is yet to be established.", "contents": "Interaction of rat plasma very low density lipoprotein with lipoprotein lipase-rich (postheparin) plasma. Incubation of 125I-labeled very low density lipoprotein (VLDL) with lipoprotein lipase-rich (postheparin) plasma obtained from intact or supradiaphragmatic rats resulted in the transfer of more than 80% of apoprotein C from VLDL to high density lipoprotein (HDL), whereas apoprotein B was associated with lipoprotein of density less than 1.019 g/ml (intermediate lipoprotein). The transfer of 125I-labeled apoprotein C from VLDL to HDL increased with time and decreased in proportion to the amount of VLDL in the incubation system. A relationship was established between the content of triglycerides and apoprotein C in VLDL, whereas the amount of apoprotein C in VLDL was independent of that of other apoproteins, especially apoprotein B. The injection of heparin to rats preinjected with 125I-labeled VLDL caused apoprotein interconversions similar to those observed in vitro. The intermediate lipoprotein was relatively rich in apoprotein B, apoprotein VS-2, cholesterol, and phospholipids and poor in triglycerides and apoprotein C. The mean diameter of intermediate lipoprotein was 269 A (compared with 427 A, the mean Sf rate was 30.5 (compared with 115), and the mean weight was 7.0 X 10(6) daltons (compared with 23.1 X 10(6)). From these data it was possible to calculate the mass of lipids and apoproteins in single lipoprotein particles. The content of apoprotein B in both particles was virtually identical, 0.7 X 10(6) daltons. The relative amount of all other constituents in intermediate lipoprotein was lower than in VLDL: triglycerides, 22%; free cholesterol, 37%; esterified cholesterol, 68%; phospholipids, 41%; apoprotein C, 7%, and VS-2 apoprotein, 60%. The data indicate that (a) one and only one intermediate lipoprotein is formed from each VLDL particle, and (b) during the formation of the intermediate lipoprotein all lipid and apoprotein components other than apoprotein B leave the density range of VLDL to a varying degree. Whether these same changes occur during the clearance of VLDL in vivo is yet to be established."} {"id": "PMID:170351", "title": "Studies on the metabolism of rat serum very low density apolipoprotein.", "content": "There was a rapid transfer of radioactive peptides to other lipoprotein fractions during the first 30 min after the intravenous injection of 125I-labeled rat very low density lipoprotein (VLDL) into rats. After this initial redistribution of radioactivity, label disappeared slowly from all lipoprotein fractions. The disappearance of 125I-labeled human VLDL injected into rats was the same as that of rat VLDL. Most of the radioactivity transferred from VLDL to low density (LDL) and high density (HDL) lipoproteins was associated with two peptides, identified in these studies by polyacrylamide gel electrophoresis as zone IVa and IVb peptides (fast-migrating peptides, possibly analogous to some human C apolipoproteins), although radioactivity initially associated with zone I (analogous to human apolipoprotein B) and zone III (not characterized) was also transferred to LDL and HDL. That the transfer of label from VLDL to LDL and HDL primarily involved small molecular weight peptides was confirmed in studies using VLDL predominantly labeled in these peptides by in vitro transfer from 125I-labeled HDL. Both zone I and zone IV radioactivity was rapidly removed from VLDL during the first 5 min after injection. However, although most of the zone IV radioactivity was recovered in LDL and HDL, only 12% of the label lost from zone I of VLDL was recovered in other lipoproteins, with the remainder presumably having been cleared from the plasma compartment. We have concluded that, during catabolism of rat VLDL apoprotein, there is a rapid transfer of small molecular weight peptides to both LDL and HDL. During the catabolic process, most of the VLDL is rapidly removed from the circulation, with only a small portion being transformed into LDL molecules.", "contents": "Studies on the metabolism of rat serum very low density apolipoprotein. There was a rapid transfer of radioactive peptides to other lipoprotein fractions during the first 30 min after the intravenous injection of 125I-labeled rat very low density lipoprotein (VLDL) into rats. After this initial redistribution of radioactivity, label disappeared slowly from all lipoprotein fractions. The disappearance of 125I-labeled human VLDL injected into rats was the same as that of rat VLDL. Most of the radioactivity transferred from VLDL to low density (LDL) and high density (HDL) lipoproteins was associated with two peptides, identified in these studies by polyacrylamide gel electrophoresis as zone IVa and IVb peptides (fast-migrating peptides, possibly analogous to some human C apolipoproteins), although radioactivity initially associated with zone I (analogous to human apolipoprotein B) and zone III (not characterized) was also transferred to LDL and HDL. That the transfer of label from VLDL to LDL and HDL primarily involved small molecular weight peptides was confirmed in studies using VLDL predominantly labeled in these peptides by in vitro transfer from 125I-labeled HDL. Both zone I and zone IV radioactivity was rapidly removed from VLDL during the first 5 min after injection. However, although most of the zone IV radioactivity was recovered in LDL and HDL, only 12% of the label lost from zone I of VLDL was recovered in other lipoproteins, with the remainder presumably having been cleared from the plasma compartment. We have concluded that, during catabolism of rat VLDL apoprotein, there is a rapid transfer of small molecular weight peptides to both LDL and HDL. During the catabolic process, most of the VLDL is rapidly removed from the circulation, with only a small portion being transformed into LDL molecules."} {"id": "PMID:170352", "title": "Increase in plasma testosterone concentrations after injection of adrenocorticotrophin into the boar.", "content": "Injection of a 'rapid-acting' preparation of porcine adrenocorticotrophic hormone (ACTH) into three boars resulted in a rapid rise in plasma testosterone levels which accompanied the expected rise in plasma corticosteroids. Urinary dehydroepiandrosterone (DHA) levels were measured in one boar and were found to be raised also. The results suggest that the effect involved enhaced testicular steroid activity and was related to the dosage of ACTH employed. This action of ACTH is thought to be mediated through the adrenal cortex since injection of cortisol elecited a rise in testosterone similar to that observed after injection of ACTH. ACTH had no effect on testosterone levels in a castrated boar. When a 'long-acting' preparation of ACTH was administered to two boars twice daily for 5 days, testosterone levels were depressed. It was concluded that ACTH may bring about an increase or a decrease in plasma testosterone levels in the boar depending upon the length of time increased levels of ACTH are present in the circulation.", "contents": "Increase in plasma testosterone concentrations after injection of adrenocorticotrophin into the boar. Injection of a 'rapid-acting' preparation of porcine adrenocorticotrophic hormone (ACTH) into three boars resulted in a rapid rise in plasma testosterone levels which accompanied the expected rise in plasma corticosteroids. Urinary dehydroepiandrosterone (DHA) levels were measured in one boar and were found to be raised also. The results suggest that the effect involved enhaced testicular steroid activity and was related to the dosage of ACTH employed. This action of ACTH is thought to be mediated through the adrenal cortex since injection of cortisol elecited a rise in testosterone similar to that observed after injection of ACTH. ACTH had no effect on testosterone levels in a castrated boar. When a 'long-acting' preparation of ACTH was administered to two boars twice daily for 5 days, testosterone levels were depressed. It was concluded that ACTH may bring about an increase or a decrease in plasma testosterone levels in the boar depending upon the length of time increased levels of ACTH are present in the circulation."} {"id": "PMID:170353", "title": "Serum follicle-stimulating hormone and luteinizing hormone levels in male rats with experimentally induced damage of the germinal epitheilum.", "content": "The effect of the depletion of germinal cells from the seminiferous tubules on serum follicle-stimulating (FSH) and luteinizing (LH) was studied in young male rats. A single administration of 1-(N,N-diethylcarbamylmethyl)-2-4-dinitropyrrole (ORF 1616) seemed to damage primary spermatocytes and especially young spermatids. Whenever young spermatids (stages 1-8) were absent or at least decreased in number, a significant increase in serum FSH, and in some cases serum LH, was detected. The administration of another drug, bis (dichloroacetyl) diamine (WIN 18446) for 21 consecutive days induced a depletion of primary spermatocytes in the seminiferous tubules, which was followed by a depletion of spermatids, due to the lack of spermatocytes to generat them. By the time the seminiferous tubules showed partial or total disapperance of young spermatids, serum FSH and in some cases also serum LH levels were significantly raised. It is concluded that the germinal epithelium of rat testes exerts some kind of control on serum gonadotrophin levels. Young spermatids seem to be involved in this regulation.", "contents": "Serum follicle-stimulating hormone and luteinizing hormone levels in male rats with experimentally induced damage of the germinal epitheilum. The effect of the depletion of germinal cells from the seminiferous tubules on serum follicle-stimulating (FSH) and luteinizing (LH) was studied in young male rats. A single administration of 1-(N,N-diethylcarbamylmethyl)-2-4-dinitropyrrole (ORF 1616) seemed to damage primary spermatocytes and especially young spermatids. Whenever young spermatids (stages 1-8) were absent or at least decreased in number, a significant increase in serum FSH, and in some cases serum LH, was detected. The administration of another drug, bis (dichloroacetyl) diamine (WIN 18446) for 21 consecutive days induced a depletion of primary spermatocytes in the seminiferous tubules, which was followed by a depletion of spermatids, due to the lack of spermatocytes to generat them. By the time the seminiferous tubules showed partial or total disapperance of young spermatids, serum FSH and in some cases also serum LH levels were significantly raised. It is concluded that the germinal epithelium of rat testes exerts some kind of control on serum gonadotrophin levels. Young spermatids seem to be involved in this regulation."} {"id": "PMID:170354", "title": "Re-introduction and evaluation of an accurate, high capacity bioassay for melanocyte-stimulating hormone using the skin of Anolis carolinensis in vitro.", "content": "A simple and rapid assay for the quantitative determination of melanocyte-stimulating hormone (MSH) activity, using skin fragments of the lizard Anolis carolinensis in vitro, is described in detail. This assay, in which a quantal response (e.g. induction of a brownish-green colour) can be detected by visual observation, allows determination of MSH activity in up to 50 samples/day by one person, using the skin of one lizard. The mean dose found to induce this colour change was 0-15 ng synthetic alpha-MSH/ml (range 0-02-0-5 ng/ml). The assays shows high accuracy, reproducibility and specificity. Anterior and posterior lobe hormones as well as pituitary catecholamines do not interfere with the determination of pituitary MSH activitymthe method is compared with the assay using hypophysectomized frogs (Rana pipiens) in vivo. Determinations of MSH in pituitary extracts by both methods gave quantitatively similar results when determined with alpha-MSH as the reference substance. However, when beta-seryl MSH was used as a reference, the two assays gave different results for the MSH activity of the pituitary extractsmthis indicates that MSH from the rat pituitary gland has a biological activity similar to that of alpha-MSH rather than to that of beta-seryl MSH.", "contents": "Re-introduction and evaluation of an accurate, high capacity bioassay for melanocyte-stimulating hormone using the skin of Anolis carolinensis in vitro. A simple and rapid assay for the quantitative determination of melanocyte-stimulating hormone (MSH) activity, using skin fragments of the lizard Anolis carolinensis in vitro, is described in detail. This assay, in which a quantal response (e.g. induction of a brownish-green colour) can be detected by visual observation, allows determination of MSH activity in up to 50 samples/day by one person, using the skin of one lizard. The mean dose found to induce this colour change was 0-15 ng synthetic alpha-MSH/ml (range 0-02-0-5 ng/ml). The assays shows high accuracy, reproducibility and specificity. Anterior and posterior lobe hormones as well as pituitary catecholamines do not interfere with the determination of pituitary MSH activitymthe method is compared with the assay using hypophysectomized frogs (Rana pipiens) in vivo. Determinations of MSH in pituitary extracts by both methods gave quantitatively similar results when determined with alpha-MSH as the reference substance. However, when beta-seryl MSH was used as a reference, the two assays gave different results for the MSH activity of the pituitary extractsmthis indicates that MSH from the rat pituitary gland has a biological activity similar to that of alpha-MSH rather than to that of beta-seryl MSH."} {"id": "PMID:170355", "title": "Effects of cadmium of the hydro-osmotic and natriferic responses to the toad bladder to vasopressin.", "content": "Cadmium, 10(-3) mol/l on the mucosal or 10(-5) mol/l on the serosal side of the toad urinary bladder, inhibits the hydro-osmotic effect of vasopressin. This inhibition is irreversible. The osmotic transfer of water in the absence of vasopressin was unaffected by the presence of the Cd2+. The hydro-osmotic response to cyclic AMP was also reduced by the Cd2+, but the response due to hypertonicity of the serosal bathing solution was unaffected. The short-circuit current (reflecting active transmural Na+ transport) was inhibited by 10(-3) mol Cd2+/l on the serosa, but was increased by 10(-3) mol/l at the mucosa or 10(-4) mol/l at the serosa. The natriferic response of the bladder to vasopressin was unaffected when Cd2+ was present under conditions that inhibited the hydro-osmotic response, further emphasizing that separate effector mechamisms may be involved for each effect.", "contents": "Effects of cadmium of the hydro-osmotic and natriferic responses to the toad bladder to vasopressin. Cadmium, 10(-3) mol/l on the mucosal or 10(-5) mol/l on the serosal side of the toad urinary bladder, inhibits the hydro-osmotic effect of vasopressin. This inhibition is irreversible. The osmotic transfer of water in the absence of vasopressin was unaffected by the presence of the Cd2+. The hydro-osmotic response to cyclic AMP was also reduced by the Cd2+, but the response due to hypertonicity of the serosal bathing solution was unaffected. The short-circuit current (reflecting active transmural Na+ transport) was inhibited by 10(-3) mol Cd2+/l on the serosa, but was increased by 10(-3) mol/l at the mucosa or 10(-4) mol/l at the serosa. The natriferic response of the bladder to vasopressin was unaffected when Cd2+ was present under conditions that inhibited the hydro-osmotic response, further emphasizing that separate effector mechamisms may be involved for each effect."} {"id": "PMID:170356", "title": "Differentiation of photoreceptors in cultured optic vesicles from embryos of Rana esculenta.", "content": "Optic vesicles from embryos of Rana esculenta at a stage corresponding to stage 19 in the development of Rana pipiens were cultured for 15 days. The eyes which differentiated in vitro were much smaller than controls of the same age, due partly to the absence of the vitreous body. In many specimens a well-stratified retina surrounded by a layer of pigmented cells was found. The features of all the components of the retinal layers are described. The complete differentiation of photoreceptors, including their outer segments, is the most interesting result obtained in these organ cultures, and is in contrast with the observations previously reported for retinal tissue cultures. The authors suggest that the source of the material (amphibia instead of birds or mammals) is the main reason for this discrepancy. Frog embryo cells are practically self-sufficient since they are endowed with nutritional substances, amongst which Vit. A and antioxidative agents (Vit. E and ascorbic acid) have been indicated as the most important factors for the structural organization and integrity of the outer segments. The role played by the pigment epithelium is also discussed.", "contents": "Differentiation of photoreceptors in cultured optic vesicles from embryos of Rana esculenta. Optic vesicles from embryos of Rana esculenta at a stage corresponding to stage 19 in the development of Rana pipiens were cultured for 15 days. The eyes which differentiated in vitro were much smaller than controls of the same age, due partly to the absence of the vitreous body. In many specimens a well-stratified retina surrounded by a layer of pigmented cells was found. The features of all the components of the retinal layers are described. The complete differentiation of photoreceptors, including their outer segments, is the most interesting result obtained in these organ cultures, and is in contrast with the observations previously reported for retinal tissue cultures. The authors suggest that the source of the material (amphibia instead of birds or mammals) is the main reason for this discrepancy. Frog embryo cells are practically self-sufficient since they are endowed with nutritional substances, amongst which Vit. A and antioxidative agents (Vit. E and ascorbic acid) have been indicated as the most important factors for the structural organization and integrity of the outer segments. The role played by the pigment epithelium is also discussed."} {"id": "PMID:170357", "title": "Nicotinamide adenine dinucleotide levels in chick limb mesodermal cells in vitro: effects of 3-acetylpyridine and nicotinamide.", "content": "The studies reported here show that in cultures of developing mesodermal cells, chondrogenic expression is associated with a progressive decline in cellular NAD+ levels. Furthermore, reduced cellular NAD+ levels resulting from exposure to the nicotinamide analog 3-acetylpyridine are correlated with a 2- to 100-fold potentiation of chondrogenic expression. Conversely, elevated NAD+ levels resulting from exposure to nicotinamide alone are correlated with inhibition of chondrogenic expression. These data are consistent with the hypothesis that pyridine nucleotides, or some derivative thereof, play a central role in the control of muscle and cartilage development in embryonic chick limbs.", "contents": "Nicotinamide adenine dinucleotide levels in chick limb mesodermal cells in vitro: effects of 3-acetylpyridine and nicotinamide. The studies reported here show that in cultures of developing mesodermal cells, chondrogenic expression is associated with a progressive decline in cellular NAD+ levels. Furthermore, reduced cellular NAD+ levels resulting from exposure to the nicotinamide analog 3-acetylpyridine are correlated with a 2- to 100-fold potentiation of chondrogenic expression. Conversely, elevated NAD+ levels resulting from exposure to nicotinamide alone are correlated with inhibition of chondrogenic expression. These data are consistent with the hypothesis that pyridine nucleotides, or some derivative thereof, play a central role in the control of muscle and cartilage development in embryonic chick limbs."} {"id": "PMID:170358", "title": "Differential stimulation of murine lymphoma growth in vitro by normal and BCG-activated macrophages.", "content": "Peritoneal macrophages from mice infected with Bacille Calmette-Gu\u00e9rin (BCG) and from normal mice were examined for their effects in vitro on thymidine uptake by 10 murine lymphomas, a murine fibroblast line, and a guinea pig hepatoma. Only the murine fibroblast line showed growth inhibition in the presence of BCG macrophages. For the majority of tumors, normal macrophages were profoundly stimulatory to tumor cell DNA synthesis, while BCG macrophages were much less stimulatory, without being frankly inhibitory. The effect of 2-mercaptoethanol on tumor cell growth was also studied. All lymphomas stimulated to grow more rapidly in vitro by normal macrophages were stimulated to a similar degree by 2-mercaptoethanol.", "contents": "Differential stimulation of murine lymphoma growth in vitro by normal and BCG-activated macrophages. Peritoneal macrophages from mice infected with Bacille Calmette-Gu\u00e9rin (BCG) and from normal mice were examined for their effects in vitro on thymidine uptake by 10 murine lymphomas, a murine fibroblast line, and a guinea pig hepatoma. Only the murine fibroblast line showed growth inhibition in the presence of BCG macrophages. For the majority of tumors, normal macrophages were profoundly stimulatory to tumor cell DNA synthesis, while BCG macrophages were much less stimulatory, without being frankly inhibitory. The effect of 2-mercaptoethanol on tumor cell growth was also studied. All lymphomas stimulated to grow more rapidly in vitro by normal macrophages were stimulated to a similar degree by 2-mercaptoethanol."} {"id": "PMID:170359", "title": "Glycogen metabloism in the developing chick glycogen body: functional significance of the direct oxidative pathway.", "content": "Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glucose-6-phosphatase were quantitatively determined for the first time in glycogen body tissue from late embryonic and neonatal chicks. For comparative purposes, the activities of these enzymes were examined also in liver and skeletal muscle from pre- and post-hatched chicks. The present data show that both the embryonic and neonatal glycogen body lack glucose-6-phosphatase, but contain relatively high levels of glucose-6-phosphate dehydrogenase. The activity of each dehydrogenase in either embryonic or neonatal glycogen body tissue is two- to five-fold greater than that found in muscle or liver from pre- or post-hatched chicks. The relatively high activities observed for both dehydrogenases in the glycogen body, together with the absence of glucose-6-phosphatase activity in that tissue, suggest that the direct oxidative pathway (pentose phosphate cycle) of glucose metabolism is a functionally significant route for glycogen utilization in the glycogen body. It is hypothesized that the glycogen body is metabolically linked to lipid synthesis and myelin formation in the central nervous system of the avian embryo.", "contents": "Glycogen metabloism in the developing chick glycogen body: functional significance of the direct oxidative pathway. Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glucose-6-phosphatase were quantitatively determined for the first time in glycogen body tissue from late embryonic and neonatal chicks. For comparative purposes, the activities of these enzymes were examined also in liver and skeletal muscle from pre- and post-hatched chicks. The present data show that both the embryonic and neonatal glycogen body lack glucose-6-phosphatase, but contain relatively high levels of glucose-6-phosphate dehydrogenase. The activity of each dehydrogenase in either embryonic or neonatal glycogen body tissue is two- to five-fold greater than that found in muscle or liver from pre- or post-hatched chicks. The relatively high activities observed for both dehydrogenases in the glycogen body, together with the absence of glucose-6-phosphatase activity in that tissue, suggest that the direct oxidative pathway (pentose phosphate cycle) of glucose metabolism is a functionally significant route for glycogen utilization in the glycogen body. It is hypothesized that the glycogen body is metabolically linked to lipid synthesis and myelin formation in the central nervous system of the avian embryo."} {"id": "PMID:170362", "title": "The synthesis of beta-galactosidase by constitutive and other regulatory mutants of Escherichia coli in chemostat culture.", "content": "The synthesis of beta-galactosidase by an E. coli constitutive mutant was examined in a chemostat using glucose-, glycerol-, succinate- or N-limited growth media. Except for glucose-grown bacteria, the steady-state intracellular level of beta-galactosidase was maximal at dilution rates between 0-2 and 0-3 h-1. At higher dilution rates enzyme synthesis was reduced by catabolite repression, which could be relieved by the addition of cyclic AMP. With a catabolite-resistant mutant (UV5c), no decrease in enzyme level at high dilution rates were observed. All mutants examined were constitutive and gave decreased enzyme levels at low dilution rates, with the exception of lac-/F'lac UV5c mutants where the enzyme levels rose at low dilution rates. Hyper-producing mutants were isolated but were unstable. A constitutive mutant growing on glycerol-limited media was considered the most suitable for large-scale production of beta-galactosidase in a chemostat.", "contents": "The synthesis of beta-galactosidase by constitutive and other regulatory mutants of Escherichia coli in chemostat culture. The synthesis of beta-galactosidase by an E. coli constitutive mutant was examined in a chemostat using glucose-, glycerol-, succinate- or N-limited growth media. Except for glucose-grown bacteria, the steady-state intracellular level of beta-galactosidase was maximal at dilution rates between 0-2 and 0-3 h-1. At higher dilution rates enzyme synthesis was reduced by catabolite repression, which could be relieved by the addition of cyclic AMP. With a catabolite-resistant mutant (UV5c), no decrease in enzyme level at high dilution rates were observed. All mutants examined were constitutive and gave decreased enzyme levels at low dilution rates, with the exception of lac-/F'lac UV5c mutants where the enzyme levels rose at low dilution rates. Hyper-producing mutants were isolated but were unstable. A constitutive mutant growing on glycerol-limited media was considered the most suitable for large-scale production of beta-galactosidase in a chemostat."} {"id": "PMID:170363", "title": "Enzymic activity of purified plasma membranes from the yeast and mycelial forms of Candida albicans.", "content": "Plasma membranes were isolated from the yeast and mycelial forms of Candida albicans as described previously (Marriott, 1975) and examined for the presence of several enzymes. Measurement of specific activities showed enrichment of Mg2+-dependent and Ma+/K+-stimulated Mg2+-dependent adenosine triphosphatase and mannan synthetase, in the plasma membrane fractions from both morphological forms of the organism. However, acid and alkaline phosphatase, NADH oxidase and 5'-nucleotidase showed no such specific location.", "contents": "Enzymic activity of purified plasma membranes from the yeast and mycelial forms of Candida albicans. Plasma membranes were isolated from the yeast and mycelial forms of Candida albicans as described previously (Marriott, 1975) and examined for the presence of several enzymes. Measurement of specific activities showed enrichment of Mg2+-dependent and Ma+/K+-stimulated Mg2+-dependent adenosine triphosphatase and mannan synthetase, in the plasma membrane fractions from both morphological forms of the organism. However, acid and alkaline phosphatase, NADH oxidase and 5'-nucleotidase showed no such specific location."} {"id": "PMID:170364", "title": "Mutants of Salmonella typhimurium responding to cysteine or methionine: their nature and possible role in the regulation of cysteine biosynthesis.", "content": "Nineteen mutants of Salmonella typhimurium responding to either cysteine or methionine (cym) have been identified amongst cysteine (cys) and methionine (met) auxotrophs. Their growth responses to known intermediates in the related pathways of cysteine and methionine biosynthesis and complementation patterns in abortive transduction tests divided the mutants into six groups. Results of conjugation, cotransduction and deletion mapping experiments substantiated these groups, each of which carried a lesion within known cys genes. Enzyme assays on cym mutants from five of the six groups confirmed their cys gene deficiencies. Growth response and enzyme assay data were not consistent with mutants being leaky cys mutants (spared by methionine). None of eight cym mutants tested were able to convert [35S]methionine into [35S]cysteine. Selenate specifically inhibits the early enzymes of cysteine synthesis. In cym mutants this inhibition was relieved by cysteine but not by methionine, indicating that cym mutants require active cys enzymes for growth on methionine. There was evidence that methionine stimulated in vivo activity of cys enzymes in a cym mutant. Resistance to inhibition by 1,2,4-triazole results in reduced levels of the O-acetyl serine sulphydrylase. In cym mutants triazole resistance gave unstable suppression of the cym phenotype. Cym mutants may result from mutation in regulatory regions common to each of the cys genes, with the precise role of methionine as yet unknown.", "contents": "Mutants of Salmonella typhimurium responding to cysteine or methionine: their nature and possible role in the regulation of cysteine biosynthesis. Nineteen mutants of Salmonella typhimurium responding to either cysteine or methionine (cym) have been identified amongst cysteine (cys) and methionine (met) auxotrophs. Their growth responses to known intermediates in the related pathways of cysteine and methionine biosynthesis and complementation patterns in abortive transduction tests divided the mutants into six groups. Results of conjugation, cotransduction and deletion mapping experiments substantiated these groups, each of which carried a lesion within known cys genes. Enzyme assays on cym mutants from five of the six groups confirmed their cys gene deficiencies. Growth response and enzyme assay data were not consistent with mutants being leaky cys mutants (spared by methionine). None of eight cym mutants tested were able to convert [35S]methionine into [35S]cysteine. Selenate specifically inhibits the early enzymes of cysteine synthesis. In cym mutants this inhibition was relieved by cysteine but not by methionine, indicating that cym mutants require active cys enzymes for growth on methionine. There was evidence that methionine stimulated in vivo activity of cys enzymes in a cym mutant. Resistance to inhibition by 1,2,4-triazole results in reduced levels of the O-acetyl serine sulphydrylase. In cym mutants triazole resistance gave unstable suppression of the cym phenotype. Cym mutants may result from mutation in regulatory regions common to each of the cys genes, with the precise role of methionine as yet unknown."} {"id": "PMID:170365", "title": "Catabolite repression of Pseudomonas aeruginosa amidase: the effect of carbon source on amidase synthesis.", "content": "Synthesis of the Pseudomonas aeruginosa aliphatic amidase was repressed severely by succinate and malate and less severely by glucose, acetate or lactate. Amidase synthesis in inducible and constitutive strains was stimulated by cyclic AMP, which also gave partial relief to catabolite repression produced by the addition of lactate to cultures growing in pyruvate medium. Mutants which were resistant to catabolite repression were isolated from succinate+lactamide medium.", "contents": "Catabolite repression of Pseudomonas aeruginosa amidase: the effect of carbon source on amidase synthesis. Synthesis of the Pseudomonas aeruginosa aliphatic amidase was repressed severely by succinate and malate and less severely by glucose, acetate or lactate. Amidase synthesis in inducible and constitutive strains was stimulated by cyclic AMP, which also gave partial relief to catabolite repression produced by the addition of lactate to cultures growing in pyruvate medium. Mutants which were resistant to catabolite repression were isolated from succinate+lactamide medium."} {"id": "PMID:170366", "title": "Catabolite repression of Pseudomonas aeruginosa amidase: isolation of promotor mutants.", "content": "Among mutants of Pseudomonas aeruginosa isolated from fluoroacetamide medium were some which synthesized amidase at about 5% of the rate of the parent constitutive strain, PAC101. Seven fluoroacetamide-resistant mutants with low amidase activity gave rise to secondary mutant strains on succinate+butyramide plates. One appeared to be an 'up-promotor' mutant and synthesized amidase at a high rate. This mutant, PAC433, was not stimulated by cyclic-AMP and was much less sensitive to catabolite repression by succinate. The mutation conferring resistance to catabolite repression was cotransduced at a frequency of 96% (26/27) with the amidase genes amiR, amiE. Five other revertants had catabolite repression-resistance mutations which were linked to the amidase genes and these also were probably promotor mutants. One strain had a mutation conferring resistance to catabolite repression which was unlinked to the amidase genes.", "contents": "Catabolite repression of Pseudomonas aeruginosa amidase: isolation of promotor mutants. Among mutants of Pseudomonas aeruginosa isolated from fluoroacetamide medium were some which synthesized amidase at about 5% of the rate of the parent constitutive strain, PAC101. Seven fluoroacetamide-resistant mutants with low amidase activity gave rise to secondary mutant strains on succinate+butyramide plates. One appeared to be an 'up-promotor' mutant and synthesized amidase at a high rate. This mutant, PAC433, was not stimulated by cyclic-AMP and was much less sensitive to catabolite repression by succinate. The mutation conferring resistance to catabolite repression was cotransduced at a frequency of 96% (26/27) with the amidase genes amiR, amiE. Five other revertants had catabolite repression-resistance mutations which were linked to the amidase genes and these also were probably promotor mutants. One strain had a mutation conferring resistance to catabolite repression which was unlinked to the amidase genes."} {"id": "PMID:170367", "title": "Differential induction of tumour antigens by transformation-defective virus mutants.", "content": "Normal rat kidney cells infected by a variety of transformation-defective temperature-sensitive avian leukosis sarcoma virus mutants were tested for the expression of transformation characteristics at permissive and restrictive temperature. Morphology, growth behaviour and agglutinability by concanavalin A corresponded fully to the phenotype of the infected cells: at permissive temperature the cells resembled wild type virus transformed cells, whereas when grown under restrictive conditions they became virtually indistinguishable from normal cells. The quantitative expression of allo- or xenogeneic cell surface antigens was not significantly affected by the phenotype of the cells. Two out of the five tested mutants induced tumour antigens in the expected temperature-dependent manner, whereas the other three mutants were able to induce tumour-specific cell surface antigens even in the revertant cells cultured at the restrictive temperature. These findings extend previous results about tumour antigen induction in mutant-infected cells of the natural host, the chicken embryo fibroblasts. The value of transformation-defective tumour antigen-positive mutants for vaccination purposes will be discussed.", "contents": "Differential induction of tumour antigens by transformation-defective virus mutants. Normal rat kidney cells infected by a variety of transformation-defective temperature-sensitive avian leukosis sarcoma virus mutants were tested for the expression of transformation characteristics at permissive and restrictive temperature. Morphology, growth behaviour and agglutinability by concanavalin A corresponded fully to the phenotype of the infected cells: at permissive temperature the cells resembled wild type virus transformed cells, whereas when grown under restrictive conditions they became virtually indistinguishable from normal cells. The quantitative expression of allo- or xenogeneic cell surface antigens was not significantly affected by the phenotype of the cells. Two out of the five tested mutants induced tumour antigens in the expected temperature-dependent manner, whereas the other three mutants were able to induce tumour-specific cell surface antigens even in the revertant cells cultured at the restrictive temperature. These findings extend previous results about tumour antigen induction in mutant-infected cells of the natural host, the chicken embryo fibroblasts. The value of transformation-defective tumour antigen-positive mutants for vaccination purposes will be discussed."} {"id": "PMID:170368", "title": "Clonal variation of the mouse cells in the endogenous C-type virus induction by 5-iodo-2'-deoxyuridine.", "content": "Using an MLg cell line originating from a single newborn ddY mouse, N-tropic C-type virus able to infect the cells or origin was induced by 5-iodo-2'-deoxyuridine (IUdR). All the clones isolated from the MLg cell line released the virus after IUdR-treatment. There was more than a 100-fold difference in the virus inducibility between the highly and lowly inducible clones. The [125I]IUdR incorporation was, however, the same for the both types of clones. When the induced virus was titrat-d in the S+L-C182 cells, the XC plaque titre was about tenfold higher than murine sarcoma virus rescue focus titre.", "contents": "Clonal variation of the mouse cells in the endogenous C-type virus induction by 5-iodo-2'-deoxyuridine. Using an MLg cell line originating from a single newborn ddY mouse, N-tropic C-type virus able to infect the cells or origin was induced by 5-iodo-2'-deoxyuridine (IUdR). All the clones isolated from the MLg cell line released the virus after IUdR-treatment. There was more than a 100-fold difference in the virus inducibility between the highly and lowly inducible clones. The [125I]IUdR incorporation was, however, the same for the both types of clones. When the induced virus was titrat-d in the S+L-C182 cells, the XC plaque titre was about tenfold higher than murine sarcoma virus rescue focus titre."} {"id": "PMID:170369", "title": "Derivation of mouse sarcoma virus (Kirsten) by acquisition of genes from heterologous host.", "content": "The technique of virus RNA-cellular DNA hybridization in solution with DNA excess was used to compared the nucleotide sequences of the 70 S RNA genome of the Kirsten mouse sarcoma virus (Ki-MSV) with that of mouse erythroblastosis virus (MEV) which gave rise to Ki-MSV after in vivo propagation in rat. It is suggested that a loss of about 30% of the genomic sequences of MEV with a concomitant gain of roughly equal amounts of rat-specific sequences in a genetically stable recombinant state led to the formation of Ki-MSV.", "contents": "Derivation of mouse sarcoma virus (Kirsten) by acquisition of genes from heterologous host. The technique of virus RNA-cellular DNA hybridization in solution with DNA excess was used to compared the nucleotide sequences of the 70 S RNA genome of the Kirsten mouse sarcoma virus (Ki-MSV) with that of mouse erythroblastosis virus (MEV) which gave rise to Ki-MSV after in vivo propagation in rat. It is suggested that a loss of about 30% of the genomic sequences of MEV with a concomitant gain of roughly equal amounts of rat-specific sequences in a genetically stable recombinant state led to the formation of Ki-MSV."} {"id": "PMID:170370", "title": "Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon.", "content": "The effect of interferon on expression of Epstein-Barr virus (EBV) early gene functions was investigated. The 'early antigen' synthesis which follows either EBV superinfection of established lymphoid cell lines or 5'-iododeoxyuridine activation of the intrinsic EBV genomes harboured by these cells could be suppressed with interferon. In contrast, the spontaneous early antigen expression that occurs in a few per cent of the cells in the producer cell lines could not be blocked with interferon. The lymphoid cell lines tested differed in their ability to acquire an antiviral state after exposure to interferon. Several cell lines were also growth inhibited by the interferon preparations. The antiviral and growth inhibitory activities of different interferon preparations could not be separated by a number of criteria.", "contents": "Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon. The effect of interferon on expression of Epstein-Barr virus (EBV) early gene functions was investigated. The 'early antigen' synthesis which follows either EBV superinfection of established lymphoid cell lines or 5'-iododeoxyuridine activation of the intrinsic EBV genomes harboured by these cells could be suppressed with interferon. In contrast, the spontaneous early antigen expression that occurs in a few per cent of the cells in the producer cell lines could not be blocked with interferon. The lymphoid cell lines tested differed in their ability to acquire an antiviral state after exposure to interferon. Several cell lines were also growth inhibited by the interferon preparations. The antiviral and growth inhibitory activities of different interferon preparations could not be separated by a number of criteria."} {"id": "PMID:170371", "title": "Spontaneous interferon production and Epstein-Barr virus antigen expression in human lymphoid cell lines.", "content": "Established human lymphoid cell lines, many of which spontaneously produce interferon, differ in the efficiency by which they allow expression of Epstein-Barr virus (EBV) lytic functions. Six EBV carrying lymphoid cell lines, selected to either be extremely susceptible or very refractory to EBV superinfection, were tested for spontaneous interferon production. Only the three cell lines which were poorly superinfectable with EBV were found to produce interferon. These same three lines could not be induced to express EBV-specific early antigens from intrinsic EBV genomes. It is suggested that interferon acts as a negative control factor affecting a cell's susceptibility to EBV.", "contents": "Spontaneous interferon production and Epstein-Barr virus antigen expression in human lymphoid cell lines. Established human lymphoid cell lines, many of which spontaneously produce interferon, differ in the efficiency by which they allow expression of Epstein-Barr virus (EBV) lytic functions. Six EBV carrying lymphoid cell lines, selected to either be extremely susceptible or very refractory to EBV superinfection, were tested for spontaneous interferon production. Only the three cell lines which were poorly superinfectable with EBV were found to produce interferon. These same three lines could not be induced to express EBV-specific early antigens from intrinsic EBV genomes. It is suggested that interferon acts as a negative control factor affecting a cell's susceptibility to EBV."} {"id": "PMID:170372", "title": "Presence of chicken cell surface antigen on Rous virus activated in heterokaryons of transformed non-permissive hamster cells and chicken cells.", "content": "Incubation with antiserum to chick embryo (CE) cells, in the presence of complement, inactivates Rous sarcoma virus (RSV) produced by heterokaryons formed by non-permissive RSV-transformed hamster cells and CE cells as well as RSV produced by heterokaryons is observed following incubation with antiserum to the transformed hamster cells, plus complement. Hence, the envelope of RSV activated in heterokaryons, as that of RSV produced by CE cells, must contain a surface antigen of the CE cell, and the virus must mature only, or preferentially, at chicken-specific sites of the heterokaryon surface.", "contents": "Presence of chicken cell surface antigen on Rous virus activated in heterokaryons of transformed non-permissive hamster cells and chicken cells. Incubation with antiserum to chick embryo (CE) cells, in the presence of complement, inactivates Rous sarcoma virus (RSV) produced by heterokaryons formed by non-permissive RSV-transformed hamster cells and CE cells as well as RSV produced by heterokaryons is observed following incubation with antiserum to the transformed hamster cells, plus complement. Hence, the envelope of RSV activated in heterokaryons, as that of RSV produced by CE cells, must contain a surface antigen of the CE cell, and the virus must mature only, or preferentially, at chicken-specific sites of the heterokaryon surface."} {"id": "PMID:170373", "title": "Analysis of defective SV40 DNA by agarose gel electrophoresis.", "content": "The SV40 DNA that was generated by undiluted passaging of the virus was analysed by agarose gel electrophoresis. Nine bands of virus DNA were distinguished and each band contained a specific size class of DNA, all shorter than the complete SV40 genome as was determined by electron microscopy measurements. A difference of 2% in length, about 100 base pairs, resulted in a clear band splitting. Two sets of undiluted passaging were established and the defective DNA in the two sets had both different and similar size classes varying in length from 96% to 73% of the unit length SV40 DNA.", "contents": "Analysis of defective SV40 DNA by agarose gel electrophoresis. The SV40 DNA that was generated by undiluted passaging of the virus was analysed by agarose gel electrophoresis. Nine bands of virus DNA were distinguished and each band contained a specific size class of DNA, all shorter than the complete SV40 genome as was determined by electron microscopy measurements. A difference of 2% in length, about 100 base pairs, resulted in a clear band splitting. Two sets of undiluted passaging were established and the defective DNA in the two sets had both different and similar size classes varying in length from 96% to 73% of the unit length SV40 DNA."} {"id": "PMID:170374", "title": "The synthesis of polyadenylated messenger RNA in herpes simplex type I virus infected BHK cells.", "content": "The pattern of polyadenylated messenger RNA (mRNA) synthesis in BHK cell monolayers, infected under defined conditions with herpes simplex type I virus has been investigated by polyacrylamide gel electrophoresis or pulse-labelled RNA isolated by oligo dT-cellulose chromatography. Two classes of mRNA molecules were synthesized in infected cells; these were not detected in uninfected cells. The rate of synthesis of the larger, 18 to 30S RNA class reached a maximum soon after injection and then declined, whereas the rate of synthesis of the 7 to 11 S RNA class did not reach a maximum until much later and did not decline. In the presence of cytosine arabinoside, the rate of mRNA synthesis in infected cells was reduced but the electrophoretic pattern remained the same.", "contents": "The synthesis of polyadenylated messenger RNA in herpes simplex type I virus infected BHK cells. The pattern of polyadenylated messenger RNA (mRNA) synthesis in BHK cell monolayers, infected under defined conditions with herpes simplex type I virus has been investigated by polyacrylamide gel electrophoresis or pulse-labelled RNA isolated by oligo dT-cellulose chromatography. Two classes of mRNA molecules were synthesized in infected cells; these were not detected in uninfected cells. The rate of synthesis of the larger, 18 to 30S RNA class reached a maximum soon after injection and then declined, whereas the rate of synthesis of the 7 to 11 S RNA class did not reach a maximum until much later and did not decline. In the presence of cytosine arabinoside, the rate of mRNA synthesis in infected cells was reduced but the electrophoretic pattern remained the same."} {"id": "PMID:170375", "title": "The effects of concanavalin A on the early events of infection by rhinovirus type 2 and poliovirus type 2.", "content": "The effect of concanavalin A (Con A) on the course of early infection of HeLa cells with purified radioactive human rhinovirus type 2 (HRV-2) or poliovirus type 2 (P-2) has been examined. Several early steps in infection were inhibited before the uncoating of parental virus. Con A, at 100 mug/ml, reduces attachment of virus when added to cells before infection. Con A also detectably slows the normal progression of adsorbed virus to tightly bound forms characterized, in the case of HRV-2, by resistance to elution by EDTA, or in a case of P-2, by isolation of a characteristic virus-membrane complex. When Con A is added together with either virus, it also inhibits cell-mediated eclipse of infectivity and the formation of non-infective subviral particles.", "contents": "The effects of concanavalin A on the early events of infection by rhinovirus type 2 and poliovirus type 2. The effect of concanavalin A (Con A) on the course of early infection of HeLa cells with purified radioactive human rhinovirus type 2 (HRV-2) or poliovirus type 2 (P-2) has been examined. Several early steps in infection were inhibited before the uncoating of parental virus. Con A, at 100 mug/ml, reduces attachment of virus when added to cells before infection. Con A also detectably slows the normal progression of adsorbed virus to tightly bound forms characterized, in the case of HRV-2, by resistance to elution by EDTA, or in a case of P-2, by isolation of a characteristic virus-membrane complex. When Con A is added together with either virus, it also inhibits cell-mediated eclipse of infectivity and the formation of non-infective subviral particles."} {"id": "PMID:170376", "title": "Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease.", "content": "Nineteen recent isolated and three laboratory strains of herpes simplex virus types 1 and 2 were tested for their ability to produce clinical signs in mice following intradermal inoculation in the ear. All viruses produced erythema at the inoculation site; this was the most sensitive clinical sign of infection. Virus multiplication in the ear tissue was similar for both types 1 and 2 up to the fifth day after inoculation but type 2 viruses persisted for longer. Latent infection was demonstrated in cervical dorsal root ganglia. Type 1 viruses required a much higher dose than type 2 to produce neurological signs and death after intradermal inoculation but the difference was less after intracerebral inoculation. Erythema of the inoculated ear recurred sporadically during several months observation in about half the mice that survived intradermal infection with a selected type 1 isolate. The presence of virus in the ear tissue during such recurrences was confirmed by electron microscopy and isolation of infectious virus. The system of ear infection in the mouse is presented as a new model for studying neurovirulence, and latent and recurrent infection with herpes simplex virus.", "contents": "Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. Nineteen recent isolated and three laboratory strains of herpes simplex virus types 1 and 2 were tested for their ability to produce clinical signs in mice following intradermal inoculation in the ear. All viruses produced erythema at the inoculation site; this was the most sensitive clinical sign of infection. Virus multiplication in the ear tissue was similar for both types 1 and 2 up to the fifth day after inoculation but type 2 viruses persisted for longer. Latent infection was demonstrated in cervical dorsal root ganglia. Type 1 viruses required a much higher dose than type 2 to produce neurological signs and death after intradermal inoculation but the difference was less after intracerebral inoculation. Erythema of the inoculated ear recurred sporadically during several months observation in about half the mice that survived intradermal infection with a selected type 1 isolate. The presence of virus in the ear tissue during such recurrences was confirmed by electron microscopy and isolation of infectious virus. The system of ear infection in the mouse is presented as a new model for studying neurovirulence, and latent and recurrent infection with herpes simplex virus."} {"id": "PMID:170377", "title": "Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels.", "content": "Treatment of L cells with 3 to 10 mM 3':5'-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined L-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP.", "contents": "Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels. Treatment of L cells with 3 to 10 mM 3':5'-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined L-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP."} {"id": "PMID:170378", "title": "Haemagglutination by avian infectious bronchitis virus-a coronavirus.", "content": "The haemagglutinating ability of three strains of IBV was investigated. It was shown that whereas strain Beaudette had no detectable haemagglutinin, both Connecticut and Massachusetts agglutinated red cells of various species. The haemagglutinin of Connecticut was detectable after sucrose gradient purification whereas that of Massachusetts required both the purification step and incubation with the enzyme phospholipase C to reveal it. The agglutination could be inhibited by specific antisera. Some studies on the nature of the red cell receptor, and the possible presence of a receptor destroying enzyme, are reported.", "contents": "Haemagglutination by avian infectious bronchitis virus-a coronavirus. The haemagglutinating ability of three strains of IBV was investigated. It was shown that whereas strain Beaudette had no detectable haemagglutinin, both Connecticut and Massachusetts agglutinated red cells of various species. The haemagglutinin of Connecticut was detectable after sucrose gradient purification whereas that of Massachusetts required both the purification step and incubation with the enzyme phospholipase C to reveal it. The agglutination could be inhibited by specific antisera. Some studies on the nature of the red cell receptor, and the possible presence of a receptor destroying enzyme, are reported."} {"id": "PMID:170379", "title": "Inhibition of human cytomegalovirus by rifampin.", "content": "Replication of human cytomegalovirus (CMV) was inhibited by 50 mug/ml of rifampin. Nevertheless, a number of functions of CMV were still expressed in the presence of rifampin, including early cell rounding, and the development of immuno-fluorescent antigen, haemadsorption antigen, complement-fixing antigen and precipitin antigens. If rifampin was kept in the culture medium for longer than 48 h, infectious virus was not synthesized, but removal of rifampin resulted in restoration of virus titre within 24 h. In parallel with the restoration of infectivity, removal of the drug resulted in a sharp increase in macromolecular synthesis, first RNA and then virus DNA. The results suggest that rifampin blocks a stage in the production of m-RNA species.", "contents": "Inhibition of human cytomegalovirus by rifampin. Replication of human cytomegalovirus (CMV) was inhibited by 50 mug/ml of rifampin. Nevertheless, a number of functions of CMV were still expressed in the presence of rifampin, including early cell rounding, and the development of immuno-fluorescent antigen, haemadsorption antigen, complement-fixing antigen and precipitin antigens. If rifampin was kept in the culture medium for longer than 48 h, infectious virus was not synthesized, but removal of rifampin resulted in restoration of virus titre within 24 h. In parallel with the restoration of infectivity, removal of the drug resulted in a sharp increase in macromolecular synthesis, first RNA and then virus DNA. The results suggest that rifampin blocks a stage in the production of m-RNA species."} {"id": "PMID:170380", "title": "Time-dependent image quality using 99mTc-pyrophosphate.", "content": "Technetium-99m-labeled pyrophosphate has proved to be a useful skeletal-imaging agent. In this study, specific areas of the skeleton were imaged at times ranging from 1/2 to 6 1/2 hr after injection of 99mTc-pyrophosphate. Count ratios between abnormal and normal bone with respect to adjacent soft tissue were obtained for selected regions of interest on computer-stored scintillation camera images. The results show that image quality improves most rapidly from 1/2 to 2 hr, but further modest gain in quality does occur on views recorded between 2 and 6 hr. All lesions detected on the later images were also observed on the early ones and the ratios of uptake between abnormal and normal bone from computer-processed scintillation camera images did not change appreciably with time after the 1/2-hr images. Our results confirm the clinical impression that overall image quality is better on views obtained at least 3 hr after injection. Further delays in imaging beyond 3-4 hr after injection probably will not result in any appreciable gain in diagnostic accuracy.", "contents": "Time-dependent image quality using 99mTc-pyrophosphate. Technetium-99m-labeled pyrophosphate has proved to be a useful skeletal-imaging agent. In this study, specific areas of the skeleton were imaged at times ranging from 1/2 to 6 1/2 hr after injection of 99mTc-pyrophosphate. Count ratios between abnormal and normal bone with respect to adjacent soft tissue were obtained for selected regions of interest on computer-stored scintillation camera images. The results show that image quality improves most rapidly from 1/2 to 2 hr, but further modest gain in quality does occur on views recorded between 2 and 6 hr. All lesions detected on the later images were also observed on the early ones and the ratios of uptake between abnormal and normal bone from computer-processed scintillation camera images did not change appreciably with time after the 1/2-hr images. Our results confirm the clinical impression that overall image quality is better on views obtained at least 3 hr after injection. Further delays in imaging beyond 3-4 hr after injection probably will not result in any appreciable gain in diagnostic accuracy."} {"id": "PMID:170381", "title": "Effect of large doses of 131I-19-iodocholesterol on metapyralone-induced adrenal cortical hyperplasia in dogs.", "content": "The potential use of 131I-19-iodocholesterol to treat ACTH excess Cushing's disease was evaluated in the dog. Three normal female dogs were given LD50 radiation doses of 131I-19-iodocholesterol without producing gross or histopathologically demonstrable change of the adrenals at autopsy 3 months later. The adrenal cortices of three dogs were made hyperplastic (to simulate the adrenal cortex in Cushing's disease) with ACTH and three with Metapyralone. In addition these six dogs were given KD50 doses of 131I-19-iodocholesterol. Three months after treatment, the adrenal glands of the ACTH-treated dogs were not enlarged, the cortex was thicker than normal, and there were no changes attributable to irradiation. At 3 months, the Metapyralone-treated dogs had enlarged adrenals, widening of the adrenal cortex, and no necrosis or other changes attributable to irradiation. It is concluded that a therapeutic trial of 131I-19-iodocholesterol in the treatment of Cushing's disease is not indicated.", "contents": "Effect of large doses of 131I-19-iodocholesterol on metapyralone-induced adrenal cortical hyperplasia in dogs. The potential use of 131I-19-iodocholesterol to treat ACTH excess Cushing's disease was evaluated in the dog. Three normal female dogs were given LD50 radiation doses of 131I-19-iodocholesterol without producing gross or histopathologically demonstrable change of the adrenals at autopsy 3 months later. The adrenal cortices of three dogs were made hyperplastic (to simulate the adrenal cortex in Cushing's disease) with ACTH and three with Metapyralone. In addition these six dogs were given KD50 doses of 131I-19-iodocholesterol. Three months after treatment, the adrenal glands of the ACTH-treated dogs were not enlarged, the cortex was thicker than normal, and there were no changes attributable to irradiation. At 3 months, the Metapyralone-treated dogs had enlarged adrenals, widening of the adrenal cortex, and no necrosis or other changes attributable to irradiation. It is concluded that a therapeutic trial of 131I-19-iodocholesterol in the treatment of Cushing's disease is not indicated."} {"id": "PMID:170382", "title": "Myocardial localization of 99mTc-pyrophosphate without evidence of acute myocardial infarction.", "content": "Localization of 99mTc-pyrophosphate in the cardiac region during routine bone scanning for metastatic tumor is discussed in two cases. Clinical information as well as electrocardiographic and serum enzyme studies did not reveal any evidence of acute myocardial injury. The cause of myocardial localization of the radiopharmaceutical is not clear in these cases.", "contents": "Myocardial localization of 99mTc-pyrophosphate without evidence of acute myocardial infarction. Localization of 99mTc-pyrophosphate in the cardiac region during routine bone scanning for metastatic tumor is discussed in two cases. Clinical information as well as electrocardiographic and serum enzyme studies did not reveal any evidence of acute myocardial injury. The cause of myocardial localization of the radiopharmaceutical is not clear in these cases."} {"id": "PMID:170384", "title": "Phagocytic capability of the kidney: a possible mechanism for renal uptake of colloid in liver-spleen scanning.", "content": "Guinea pigs were given Trypan blue or India ink i.v. and i.m. to demonstrate whether proximal convoluted tubule cells of the normal kidney have potential phagocytic capability. Circulating colloidal particles of Trypan blue solution accumulated in these cells and the accumulation was related to the particle size, dose injection, and duration of experiment. These studies suggest an explanation for the clinical observation of renal visualization with 99mTc-sulfur colloid in patients with congestive heart failure.", "contents": "Phagocytic capability of the kidney: a possible mechanism for renal uptake of colloid in liver-spleen scanning. Guinea pigs were given Trypan blue or India ink i.v. and i.m. to demonstrate whether proximal convoluted tubule cells of the normal kidney have potential phagocytic capability. Circulating colloidal particles of Trypan blue solution accumulated in these cells and the accumulation was related to the particle size, dose injection, and duration of experiment. These studies suggest an explanation for the clinical observation of renal visualization with 99mTc-sulfur colloid in patients with congestive heart failure."} {"id": "PMID:170385", "title": "Technetium-99m-methylene diphosphonate--a superior agent for skeletal imaging: comparison with other technetium complexes.", "content": "Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.", "contents": "Technetium-99m-methylene diphosphonate--a superior agent for skeletal imaging: comparison with other technetium complexes. Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents."} {"id": "PMID:170386", "title": "Tissue distribution of 14C-, 125I-, and 131I-diphenylhydantoin in the toadfish, rat, and human with insulinomas.", "content": "Carbon-14-diphenylhydantoin (DPH) concentrated maximally in pancreatic islet cells of the toadfish 10 min after its intravenous administration. The islet cell-to-acinar-tissue ratio at this time was 6:1. The islet cell-to-liver ratio was 20:1. Iodine-125-paroiodo-DPH at 10 min in the toadfish showed an islet cell-to-acinar-tissue ratio of 1.7:1 and an islet cell-to-liver ratio of 2.3:1. When 14C-DPH was given to four patients 10-17 min before removal of norma pancreatic tissue and of an insulinoma in three of the patients, the concentration of radioactivity in the insulinoma was never greater than in the pancreas and concentrations in insulinoma and pancreas were always less than in liver in the same individual. Forty-five to 90 min after administration of 131I-DPH, the liver and pancreas were delineated in three patients but the insulinoma was not imaged. Five days after administration of 131I-DPH, the concentration of 131I radioactivity in excised tissue was greater in the insulinomas than in the pancreas of two patient but not sufficient to produce positive images of the insulinoma in the pancreas.", "contents": "Tissue distribution of 14C-, 125I-, and 131I-diphenylhydantoin in the toadfish, rat, and human with insulinomas. Carbon-14-diphenylhydantoin (DPH) concentrated maximally in pancreatic islet cells of the toadfish 10 min after its intravenous administration. The islet cell-to-acinar-tissue ratio at this time was 6:1. The islet cell-to-liver ratio was 20:1. Iodine-125-paroiodo-DPH at 10 min in the toadfish showed an islet cell-to-acinar-tissue ratio of 1.7:1 and an islet cell-to-liver ratio of 2.3:1. When 14C-DPH was given to four patients 10-17 min before removal of norma pancreatic tissue and of an insulinoma in three of the patients, the concentration of radioactivity in the insulinoma was never greater than in the pancreas and concentrations in insulinoma and pancreas were always less than in liver in the same individual. Forty-five to 90 min after administration of 131I-DPH, the liver and pancreas were delineated in three patients but the insulinoma was not imaged. Five days after administration of 131I-DPH, the concentration of 131I radioactivity in excised tissue was greater in the insulinomas than in the pancreas of two patient but not sufficient to produce positive images of the insulinoma in the pancreas."} {"id": "PMID:170387", "title": "Macrocephaly in association with unusual cutaneous angiomatosis.", "content": "Ten patients are presented who demonstrate a newly recognized association of macrocephaly with unusual angiomatosis and limb asymmetry in three somewhat similar cutaneous vascular disorders: Klippel-Trenaunay-Weber syndrome, the combination of Sturge-Weber anomaly with Klippel-Trenaunay-Weber syndrome, and cutis marmorata telangiectatica congenita. The etiology of the macrocephaly in patients with these conditions is unknown. The majority (seven of ten) of these children have no evidence of central nervous system dysfunction.", "contents": "Macrocephaly in association with unusual cutaneous angiomatosis. Ten patients are presented who demonstrate a newly recognized association of macrocephaly with unusual angiomatosis and limb asymmetry in three somewhat similar cutaneous vascular disorders: Klippel-Trenaunay-Weber syndrome, the combination of Sturge-Weber anomaly with Klippel-Trenaunay-Weber syndrome, and cutis marmorata telangiectatica congenita. The etiology of the macrocephaly in patients with these conditions is unknown. The majority (seven of ten) of these children have no evidence of central nervous system dysfunction."} {"id": "PMID:170389", "title": "Sexual maturation in subjects with sickle cell anemia: studies of serum gonadotropin concentration, height, weight, and skeletal age.", "content": "Luteinizing hormone and FSH concentrations were determined in sera obtained from 20 males and 20 females, ages 5 to 16 years, with sickle cell anemia (homozygous hemoglobin S). Height, weight, bone age, and stage of sexual development were also determined. Gonadotropin concentrations were increased for stage of sexual development, suggesting transient impairment of gonadal function during the first decade of life. Increased impairment of growth during the second decade of life (18 of 26 subjects, 69%) as compared to the first decade (4 of 14 subjects, 29%) was consistent with prior deficiency of gonadal secretion of steroids. Mean bone age (11.2 +/- 2.1 year) determined in 15 subjects was significantly less than the mean chronologic age (13.0 +/- 1.8 year). Significant additional data, particularly those which would be derived from a longitudinal study, are needed to validate the preliminary hypothesis that transient impairment in gonadal function may, in part, account for the variation in sexual maturation seen in subjects with sickle cell anemia.", "contents": "Sexual maturation in subjects with sickle cell anemia: studies of serum gonadotropin concentration, height, weight, and skeletal age. Luteinizing hormone and FSH concentrations were determined in sera obtained from 20 males and 20 females, ages 5 to 16 years, with sickle cell anemia (homozygous hemoglobin S). Height, weight, bone age, and stage of sexual development were also determined. Gonadotropin concentrations were increased for stage of sexual development, suggesting transient impairment of gonadal function during the first decade of life. Increased impairment of growth during the second decade of life (18 of 26 subjects, 69%) as compared to the first decade (4 of 14 subjects, 29%) was consistent with prior deficiency of gonadal secretion of steroids. Mean bone age (11.2 +/- 2.1 year) determined in 15 subjects was significantly less than the mean chronologic age (13.0 +/- 1.8 year). Significant additional data, particularly those which would be derived from a longitudinal study, are needed to validate the preliminary hypothesis that transient impairment in gonadal function may, in part, account for the variation in sexual maturation seen in subjects with sickle cell anemia."} {"id": "PMID:170393", "title": "Biochemical and cytochemical studies of digestive-absorptive functions of esophagus, cecum, and tequment in Schistosoma mansioni: acid phosphatase and tracer studies.", "content": "Acid phosphatase activity was examined, both cytochemically and biochemically, using beta-glycerophosphate (betaGP) and p-nitrophenyl phosphate (NPP) as substrates. The hydrolysis of these substrates differs in pH optimum and sensitivity to some inhibitors. A latent component of the enzyme activity could be demonstrated with betaGP but not with NPP as substrate. These differences suggest the presence of multiple enzymes operative at acid pH in S. mansoni. Cytochemical localization of the sites of hydrolysis of these substrates shows the major activity of the digestive system to be in the posterior portion of the esophagus and in the cecum. The reaction product in the posterior esophagus is found in small dumbbell-shaped vesicles and in the basal infoldings, while in the cecum it occurs on the apical plasmalemma, basal infoldings, and in pleiomorphic vesicles. The electron-dense tracers, ferritin, peroxidase, Thorotrast, and latex beads were all ingested but none was phagocytized. Tracer material was found in some \"apparent\" vesicles with subsequently were shown by the lanthanum staining technique to be in communication with the extracellular space.", "contents": "Biochemical and cytochemical studies of digestive-absorptive functions of esophagus, cecum, and tequment in Schistosoma mansioni: acid phosphatase and tracer studies. Acid phosphatase activity was examined, both cytochemically and biochemically, using beta-glycerophosphate (betaGP) and p-nitrophenyl phosphate (NPP) as substrates. The hydrolysis of these substrates differs in pH optimum and sensitivity to some inhibitors. A latent component of the enzyme activity could be demonstrated with betaGP but not with NPP as substrate. These differences suggest the presence of multiple enzymes operative at acid pH in S. mansoni. Cytochemical localization of the sites of hydrolysis of these substrates shows the major activity of the digestive system to be in the posterior portion of the esophagus and in the cecum. The reaction product in the posterior esophagus is found in small dumbbell-shaped vesicles and in the basal infoldings, while in the cecum it occurs on the apical plasmalemma, basal infoldings, and in pleiomorphic vesicles. The electron-dense tracers, ferritin, peroxidase, Thorotrast, and latex beads were all ingested but none was phagocytized. Tracer material was found in some \"apparent\" vesicles with subsequently were shown by the lanthanum staining technique to be in communication with the extracellular space."} {"id": "PMID:170394", "title": "Relation of tegumentary phosphohydrolase to purine and pyrimidine transport in Schistosoma mansoni.", "content": "Inhibition of the saturable influx of 0.05 mM 14C-labeled adenine or adenosine by AMP in adult Schistosoma mansoni in vitro suggested hydrolysis of this nucleotide at the tegumental surface of the parasite. Adenosine liberated as a result of AMP hydrolysis was the inhibitor of uptake of labeled adenine or adenosine. Inhibition of adenosine uptake by AMP or ATP was relieved by paranitrophenyl phosphate or ammonium molybdate supporting the hypothesis of nucleotide hydrolysis at the tengumental surface. Addition of glucose-1-phosphate, glucose-6-phosphate, NaF, or cysteine did not relieve AMP inhibition of adenosine uptake indicating substrate and inhibitor specificity for the surface enzyme(s). AMP, ATP, UMP, and p-nitrophenyl are hydrolyzed, at least in part, by the same enzyme(s). Apparent absorption of labeled AMP was preceded by hydrolysis, with labeled adenosine as the actual compound absorbed, although there was a small diffusion component for absorption of intact AMP. The site of nucleotide hydrolysis in close proximity to absorption sites provides a kinetic advantage for uptake of products of adenine nucleotide hydrolysis but not for products of uracil nucleotide hydrolysis.", "contents": "Relation of tegumentary phosphohydrolase to purine and pyrimidine transport in Schistosoma mansoni. Inhibition of the saturable influx of 0.05 mM 14C-labeled adenine or adenosine by AMP in adult Schistosoma mansoni in vitro suggested hydrolysis of this nucleotide at the tegumental surface of the parasite. Adenosine liberated as a result of AMP hydrolysis was the inhibitor of uptake of labeled adenine or adenosine. Inhibition of adenosine uptake by AMP or ATP was relieved by paranitrophenyl phosphate or ammonium molybdate supporting the hypothesis of nucleotide hydrolysis at the tengumental surface. Addition of glucose-1-phosphate, glucose-6-phosphate, NaF, or cysteine did not relieve AMP inhibition of adenosine uptake indicating substrate and inhibitor specificity for the surface enzyme(s). AMP, ATP, UMP, and p-nitrophenyl are hydrolyzed, at least in part, by the same enzyme(s). Apparent absorption of labeled AMP was preceded by hydrolysis, with labeled adenosine as the actual compound absorbed, although there was a small diffusion component for absorption of intact AMP. The site of nucleotide hydrolysis in close proximity to absorption sites provides a kinetic advantage for uptake of products of adenine nucleotide hydrolysis but not for products of uracil nucleotide hydrolysis."} {"id": "PMID:170396", "title": "The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature.", "content": "1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins.", "contents": "The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature. 1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins."} {"id": "PMID:170397", "title": "Effects of chronic treatment with various neuromuscular blocking agents on the number and distribution of acetylcholine receptors in the rat diaphragm.", "content": "1. Acetylcholine receptors in the end-plate and non-end-plate areas of the rat diaphragm, after treating the animal with hemicholinium-3, alpha- or beta-bungarotoxin in vivo, were studied by their specific binding of labelled alpha-bungarotoxin. 2. Subcutaneous injection of maximum tolerable doses of hemicholinium-3 (50 mug/kg) twice daily for 7 days increased the number of extrajunctional receptors along the whole length of muscle fibre, the approximate density of receptor on muscle membrane being increased from 6/mum2 in normal diaphragm to 38/mum2. Junctional receptors were also increased in number from 2-2 x 10(7) to 2-8 x 10(7) per end-plate. 3. Five days after denervation, there were approximately 153/mum2 extrajunctional receptors and the number of receptors on the end-plate was increased by 220%. 4. Intrathoracic injection of beta-bungarotoxin (50 mug/kg) also increased the density of extrajunctional receptors to approximately 104/mum2, and the number of end-plate receptors by 140% in 5 days. The neuromuscular block was extensive and prolonged. 5. [3H]Diacetyl alpha-bungarotoxin (150 mug/kg) injected into thoracic cavity caused complete neuromuscular blockade for 12 hr. At 24 hr, the synaptic transmission was restored in 80% of the junctions with less than 10% end-plate receptors freed, whereas the safety factor for transmission in normal diaphragm was 3-5. Extrajunctional receptors appeared to increase within 24 hr. This increase continued despite the restoration of neuromuscular transmission, and the receptor density at 5 days was approximately 5l/mum2. The number of junctional receptors, however, was not increased. Repeated injection of the toxin gave the same result. 6. It is concluded that the numbers of junctional and extrajunctional acetylcholine receptors are regulated in different ways, and the possible role of acetylcholine is discussed.", "contents": "Effects of chronic treatment with various neuromuscular blocking agents on the number and distribution of acetylcholine receptors in the rat diaphragm. 1. Acetylcholine receptors in the end-plate and non-end-plate areas of the rat diaphragm, after treating the animal with hemicholinium-3, alpha- or beta-bungarotoxin in vivo, were studied by their specific binding of labelled alpha-bungarotoxin. 2. Subcutaneous injection of maximum tolerable doses of hemicholinium-3 (50 mug/kg) twice daily for 7 days increased the number of extrajunctional receptors along the whole length of muscle fibre, the approximate density of receptor on muscle membrane being increased from 6/mum2 in normal diaphragm to 38/mum2. Junctional receptors were also increased in number from 2-2 x 10(7) to 2-8 x 10(7) per end-plate. 3. Five days after denervation, there were approximately 153/mum2 extrajunctional receptors and the number of receptors on the end-plate was increased by 220%. 4. Intrathoracic injection of beta-bungarotoxin (50 mug/kg) also increased the density of extrajunctional receptors to approximately 104/mum2, and the number of end-plate receptors by 140% in 5 days. The neuromuscular block was extensive and prolonged. 5. [3H]Diacetyl alpha-bungarotoxin (150 mug/kg) injected into thoracic cavity caused complete neuromuscular blockade for 12 hr. At 24 hr, the synaptic transmission was restored in 80% of the junctions with less than 10% end-plate receptors freed, whereas the safety factor for transmission in normal diaphragm was 3-5. Extrajunctional receptors appeared to increase within 24 hr. This increase continued despite the restoration of neuromuscular transmission, and the receptor density at 5 days was approximately 5l/mum2. The number of junctional receptors, however, was not increased. Repeated injection of the toxin gave the same result. 6. It is concluded that the numbers of junctional and extrajunctional acetylcholine receptors are regulated in different ways, and the possible role of acetylcholine is discussed."} {"id": "PMID:170400", "title": "Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.", "content": "1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion.", "contents": "Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep. 1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion."} {"id": "PMID:170401", "title": "[Comparative studies of the cyclic AMP content and renewal of this nucleotide in thymic, splenic and lymph-node lymphocytes in adult rats].", "content": "Cyclic AMP (c-AMP) content and turnover were measured in pure preparations of lymphocytes obtained from thymus, spleen and lymph nodes in the Rat. The c-AMP content was determined by combining the methods of Krishna and of Thomson and Appleman, and its turnover was estimated from the activities of adenylcyclase and phosphodiesterase using 3H-adenine. The values, espressed per 10(8) cells, were the lowest for the thymus and the highest for the lymph nodes, while they were intermediary for the spleen. The differences in the c-AMP turnover between the three organs may be correlated with the extent of the mitotic activity of the corresponding lymphocytes, this activity being related inversely to the turnover of c-AMP.", "contents": "[Comparative studies of the cyclic AMP content and renewal of this nucleotide in thymic, splenic and lymph-node lymphocytes in adult rats]. Cyclic AMP (c-AMP) content and turnover were measured in pure preparations of lymphocytes obtained from thymus, spleen and lymph nodes in the Rat. The c-AMP content was determined by combining the methods of Krishna and of Thomson and Appleman, and its turnover was estimated from the activities of adenylcyclase and phosphodiesterase using 3H-adenine. The values, espressed per 10(8) cells, were the lowest for the thymus and the highest for the lymph nodes, while they were intermediary for the spleen. The differences in the c-AMP turnover between the three organs may be correlated with the extent of the mitotic activity of the corresponding lymphocytes, this activity being related inversely to the turnover of c-AMP."} {"id": "PMID:170403", "title": "Hypo-beta-lipoproteinemic agents. 1. Bicyclo[2.2.2]octyloxyaniline and its derivatives.", "content": "A new assay for agents which normalize beta-lipoproteins in cholesterol-cholic acid fed rats is described. Both lowering of serum cholesterol and of serum heparin precipitable lipoproteins (HPL) were measured at the end of the treatment period. Compounds which shifted the ratio of the decrease in favor of HPL are considered hypo-beta-lipoproteinemic. p-(1-Bicyclo[2.2.2]octyloxy)aniline and several of its derivatives proved active in this assay. The synthesis of these compounds is described.", "contents": "Hypo-beta-lipoproteinemic agents. 1. Bicyclo[2.2.2]octyloxyaniline and its derivatives. A new assay for agents which normalize beta-lipoproteins in cholesterol-cholic acid fed rats is described. Both lowering of serum cholesterol and of serum heparin precipitable lipoproteins (HPL) were measured at the end of the treatment period. Compounds which shifted the ratio of the decrease in favor of HPL are considered hypo-beta-lipoproteinemic. p-(1-Bicyclo[2.2.2]octyloxy)aniline and several of its derivatives proved active in this assay. The synthesis of these compounds is described."} {"id": "PMID:170404", "title": "17alpha-Ethyl-20alpha-and -20beta-dihydroprogesterones and other 17alpha-ethyl-substituted pregnanes as potential contragestational agents.", "content": "The 17alpha-ethyl-substituted analogs of the two epimeric 20-dihydroprogesterones, allopregnadedione and pregn-5-ene-3,20-dione, were synthesized and evaluated for their possible oral contragestational (postcoital antifertility) activity in the rat. The compounds, though bound strongly to the progesterone receptor in vitro, were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo.", "contents": "17alpha-Ethyl-20alpha-and -20beta-dihydroprogesterones and other 17alpha-ethyl-substituted pregnanes as potential contragestational agents. The 17alpha-ethyl-substituted analogs of the two epimeric 20-dihydroprogesterones, allopregnadedione and pregn-5-ene-3,20-dione, were synthesized and evaluated for their possible oral contragestational (postcoital antifertility) activity in the rat. The compounds, though bound strongly to the progesterone receptor in vitro, were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo."} {"id": "PMID:170405", "title": "Mercurial perturbation of brush border membrane permeability in rabbit ileum.", "content": "The sulfhydryl reagents Hg++ and p-chloromercuribenzene sulfonate (PCMBS) at millimolar concentrations reduced the mucosal entry of sugars and amino acids to 80-90% of control levels within several minutes. Based on 50% levels of inhibition, Hg++ proved to be 20 and 10 times as potent as PCMBS in blocking sugar and amino acid transport, respectively; both systems were equally sensitive to Hg++. Concomitant measurements of 203Hg-PCMBS demonstrated a progressive tissue uptake, which, unlike inhibition, did not saturate with increasing times of exposure, thus suggesting appreciable epithelial entry with prolonged exposures (less than 30 min at 1 mM). At similar dose levels, no significant change in mucosal Na+ entry was detected. Inhibition was not reversed by 30-min washes in cholinesalt solutions; however, 10-min exposures to dithiothreitol [10 mM] reversed Hg++ and PCMBS inhibition by 40 and 100%, respectively. Alanine and galactose influx kinetics measured at concentrations of 0-100 mM exhibited a linear or diffusional entry component in addition to the usual saturable component for both control and Hg++-treated ileum. The presence of a diffusional term in the flux equation resulted in two sets of parameters giving nearly equal fits to these measurements. It was shown that this ambiguity could be resolved by determining the change in diffusional entry with Hg++ treatment. A 20-min exposure to 0.5 mM Hg++ caused an increase from 0.050 and 0.045 to 0.064 and 0.070 cm/hr in the coefficient of diffusional entry for alanine and galactose, respectively. On the basis of this increase, it is argued that Hg++ causes a decrease in Jmax and little change in Km for both transport mechanisms. This analysis has a general bearing on kinetic measurements of transport in which passive fluxes are comparable to those mediated by specific pathways. The alanine results are consistent with bimolecular reactions between mercurial and two membrane inhibitory sites, each producing approximately 40% reduction in membrane translocation rate. The estimated reaction rate constants were 5.0 and 0.4 mM min.", "contents": "Mercurial perturbation of brush border membrane permeability in rabbit ileum. The sulfhydryl reagents Hg++ and p-chloromercuribenzene sulfonate (PCMBS) at millimolar concentrations reduced the mucosal entry of sugars and amino acids to 80-90% of control levels within several minutes. Based on 50% levels of inhibition, Hg++ proved to be 20 and 10 times as potent as PCMBS in blocking sugar and amino acid transport, respectively; both systems were equally sensitive to Hg++. Concomitant measurements of 203Hg-PCMBS demonstrated a progressive tissue uptake, which, unlike inhibition, did not saturate with increasing times of exposure, thus suggesting appreciable epithelial entry with prolonged exposures (less than 30 min at 1 mM). At similar dose levels, no significant change in mucosal Na+ entry was detected. Inhibition was not reversed by 30-min washes in cholinesalt solutions; however, 10-min exposures to dithiothreitol [10 mM] reversed Hg++ and PCMBS inhibition by 40 and 100%, respectively. Alanine and galactose influx kinetics measured at concentrations of 0-100 mM exhibited a linear or diffusional entry component in addition to the usual saturable component for both control and Hg++-treated ileum. The presence of a diffusional term in the flux equation resulted in two sets of parameters giving nearly equal fits to these measurements. It was shown that this ambiguity could be resolved by determining the change in diffusional entry with Hg++ treatment. A 20-min exposure to 0.5 mM Hg++ caused an increase from 0.050 and 0.045 to 0.064 and 0.070 cm/hr in the coefficient of diffusional entry for alanine and galactose, respectively. On the basis of this increase, it is argued that Hg++ causes a decrease in Jmax and little change in Km for both transport mechanisms. This analysis has a general bearing on kinetic measurements of transport in which passive fluxes are comparable to those mediated by specific pathways. The alanine results are consistent with bimolecular reactions between mercurial and two membrane inhibitory sites, each producing approximately 40% reduction in membrane translocation rate. The estimated reaction rate constants were 5.0 and 0.4 mM min."} {"id": "PMID:170406", "title": "The hydrosmotic effect of vasopressin: a scanning electrom-microscope study.", "content": "Scanning electron-microscopy (SEM) was used to investigate the hydrosmotic effect of vasopressin on the apical surface of urinary bladders of toads Bufo marinus. Bladders were mounted on glass chambers and water fluxes were monitored with an optical method. Tissues were fixed in 2% glutaraldehyde and processed for SEM. Three types of cells were seen on the surface of control bladders:large polygonal (granular) cells, with blunt microvilli; smaller (mitochondria-rich) cells, with longer microvilli; goblet cells. Neither exposure of the bladders to a large osmotic gradient nor exposure to vasopressin in the absence of a gradient altered appreciably the epithelial surface. In contrast, the combination of vasopressin and an osmotic gradient resulted ina conspicuous diminution of the blunt microvilli. However, the small cells with longer microvilli remained unchanged. Identical results were seen with cAMP or theophylline in the presence of an osmotic gradient. These findings suggest that the hydrosmotic effect of vasopressin is mainly exerted on the granular cells of toad bladder and confirm observations made by others with the electron-microscope.", "contents": "The hydrosmotic effect of vasopressin: a scanning electrom-microscope study. Scanning electron-microscopy (SEM) was used to investigate the hydrosmotic effect of vasopressin on the apical surface of urinary bladders of toads Bufo marinus. Bladders were mounted on glass chambers and water fluxes were monitored with an optical method. Tissues were fixed in 2% glutaraldehyde and processed for SEM. Three types of cells were seen on the surface of control bladders:large polygonal (granular) cells, with blunt microvilli; smaller (mitochondria-rich) cells, with longer microvilli; goblet cells. Neither exposure of the bladders to a large osmotic gradient nor exposure to vasopressin in the absence of a gradient altered appreciably the epithelial surface. In contrast, the combination of vasopressin and an osmotic gradient resulted ina conspicuous diminution of the blunt microvilli. However, the small cells with longer microvilli remained unchanged. Identical results were seen with cAMP or theophylline in the presence of an osmotic gradient. These findings suggest that the hydrosmotic effect of vasopressin is mainly exerted on the granular cells of toad bladder and confirm observations made by others with the electron-microscope."} {"id": "PMID:170410", "title": "Comparative ultrastructural study of four reticuloendothelias viruses.", "content": "The morphology and development of four members of the reticuloendotheliosis virus group were studied by transmission electron microscopy. Virions of duck spleen necrosis virus, duck infectious anemia virus, chicken syncytial virus, and reticuloendotheliosis virus strain T are sperical with a diameter of approximately 110 nm. They are covered with surface projections about 6 nm long and 10 nm in diameter. The center-to-center distance of surface projections is about 14 nm. The budding virions contain crescent-shaped electron-dense cores 73 nm in diameter with electron-lucent centers. After release of the virions the cores apparently become condensed to 67 nm in diameter. Virions were found budding at the plasma membrane and into smooth-walled, intracytoplasmic vesicles of productively infected cells. The distribution of budding reticuloendotheliosis viruses on cells appeared random over the cell surface, and occasionally aberrant multiple forms of budding virions were observed. The virions appear to resemble mammalian leukemia and sarcoma viruses more closely than avian leukosis-sarcoma viruses.", "contents": "Comparative ultrastructural study of four reticuloendothelias viruses. The morphology and development of four members of the reticuloendotheliosis virus group were studied by transmission electron microscopy. Virions of duck spleen necrosis virus, duck infectious anemia virus, chicken syncytial virus, and reticuloendotheliosis virus strain T are sperical with a diameter of approximately 110 nm. They are covered with surface projections about 6 nm long and 10 nm in diameter. The center-to-center distance of surface projections is about 14 nm. The budding virions contain crescent-shaped electron-dense cores 73 nm in diameter with electron-lucent centers. After release of the virions the cores apparently become condensed to 67 nm in diameter. Virions were found budding at the plasma membrane and into smooth-walled, intracytoplasmic vesicles of productively infected cells. The distribution of budding reticuloendotheliosis viruses on cells appeared random over the cell surface, and occasionally aberrant multiple forms of budding virions were observed. The virions appear to resemble mammalian leukemia and sarcoma viruses more closely than avian leukosis-sarcoma viruses."} {"id": "PMID:170411", "title": "Mapping RNase T1-resistant oligonucleotides of avian tumor virus RNAs: sarcoma-specific oligonucleotides are near the poly(A) end and oligonucleotides common to sarcoma and transformation-defective viruses are at the poly(A) end.", "content": "The large RNase T1-resistant oligonucleotides of the nondefective (nd) Rous sarcoma virus (RSV): Prague RSV of subgroup B (PR-B), PR-C and B77 of subgroup C; of their transformation-defective (td0 deletion mutants: td PR-B, td PR-C, and td B77; and of replication-defective (rd) RSV(-) were completely or partially mapped on the 30 to 40S viral RNAs. The location of a given oligonucleotide relative to the poly(A) terminus of the viral RNAs was directly deduced from the smallest size of the poly(A)-tagged RNA fragment from which it could be isolated. Identification of distinct oligonucleotides was based on their location in the electrophoretic/chromatographic fingerprint pattern and on analysis of their RNase A-resistant fragments. The following results were obtained. (i) The number of large oligonucleotides per poly(A)-tagged ffagment increased with increasing size of the fragment. This implies that the genetic map is linear and that a given RNase T1-resistant oligonucleotides has, relative to the poly(A) end, the same location on all 30 to 40S RNA subunits of a given 60 to 70S viral RNA complex, (ii) Three sarcoma-specific oligonucleotides were identified in the RNAs of Pr-B, PR-C and B77 by comparison with the RNAs of the corresponding td viruses...", "contents": "Mapping RNase T1-resistant oligonucleotides of avian tumor virus RNAs: sarcoma-specific oligonucleotides are near the poly(A) end and oligonucleotides common to sarcoma and transformation-defective viruses are at the poly(A) end. The large RNase T1-resistant oligonucleotides of the nondefective (nd) Rous sarcoma virus (RSV): Prague RSV of subgroup B (PR-B), PR-C and B77 of subgroup C; of their transformation-defective (td0 deletion mutants: td PR-B, td PR-C, and td B77; and of replication-defective (rd) RSV(-) were completely or partially mapped on the 30 to 40S viral RNAs. The location of a given oligonucleotide relative to the poly(A) terminus of the viral RNAs was directly deduced from the smallest size of the poly(A)-tagged RNA fragment from which it could be isolated. Identification of distinct oligonucleotides was based on their location in the electrophoretic/chromatographic fingerprint pattern and on analysis of their RNase A-resistant fragments. The following results were obtained. (i) The number of large oligonucleotides per poly(A)-tagged ffagment increased with increasing size of the fragment. This implies that the genetic map is linear and that a given RNase T1-resistant oligonucleotides has, relative to the poly(A) end, the same location on all 30 to 40S RNA subunits of a given 60 to 70S viral RNA complex, (ii) Three sarcoma-specific oligonucleotides were identified in the RNAs of Pr-B, PR-C and B77 by comparison with the RNAs of the corresponding td viruses..."} {"id": "PMID:170412", "title": "Detection of type A oncornavirus-like structures in chicken embryo cells after infection with Rous sarcoma virus.", "content": "Electron microscopy examination of Rous sarcoma virus-transformed chicken embryo cells revealed membrane-free nucleoids resembling type A oncornavirus. These particles were not detected in noninfected cells, nor did they accumulate in excess under conditions of glucosamine block in virus-transformed cultures.", "contents": "Detection of type A oncornavirus-like structures in chicken embryo cells after infection with Rous sarcoma virus. Electron microscopy examination of Rous sarcoma virus-transformed chicken embryo cells revealed membrane-free nucleoids resembling type A oncornavirus. These particles were not detected in noninfected cells, nor did they accumulate in excess under conditions of glucosamine block in virus-transformed cultures."} {"id": "PMID:170413", "title": "Sindbis virus inhibits phosphatidylcholine biosynthesis in BHK-21 cells.", "content": "Sindbis virus inhibits the incorporation of [methyl-3H]choline into the phospholipids of BHK-21 cells and also inhibits the activity of the enzyme that catalyzes the final reaction involved in phosphatidylcholine biosynthesis (cytidine diphosphate-choline:1,2-diacylglycerol cholinephosphotranferase; EC 2.7.8.2).", "contents": "Sindbis virus inhibits phosphatidylcholine biosynthesis in BHK-21 cells. Sindbis virus inhibits the incorporation of [methyl-3H]choline into the phospholipids of BHK-21 cells and also inhibits the activity of the enzyme that catalyzes the final reaction involved in phosphatidylcholine biosynthesis (cytidine diphosphate-choline:1,2-diacylglycerol cholinephosphotranferase; EC 2.7.8.2)."} {"id": "PMID:170414", "title": "Poly(A) on mengovirus RNA.", "content": "The content and size of the poly(A) on Mengovirus RNA grown in both mouse L cells and HeLa cells have been examined. Virion RNA from either cell line could bind to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. The size of the poly(A) on the Mengovirus RNA was independent of the host cell and averaged from 50 to 70 nucleotides.", "contents": "Poly(A) on mengovirus RNA. The content and size of the poly(A) on Mengovirus RNA grown in both mouse L cells and HeLa cells have been examined. Virion RNA from either cell line could bind to poly(U) filters and contained RNase-resistant stretches of poly(A) which could be analyzed by electrophoresis in polyacrylamide gels. The size of the poly(A) on the Mengovirus RNA was independent of the host cell and averaged from 50 to 70 nucleotides."} {"id": "PMID:170415", "title": "Acquisition of viral DNA sequences in target organs of chickens infected with avian myeloblastosis virus.", "content": "The distribution of oncornavirus DNA sequences in various tissues of normal chickens and of chickens with leukemia or kidney tumors induced by avian myeloblastosis virus (AMV) was analyzed by DNA-RNA hybridization using 35S AMV RNA as a probe. All the tissues from normal chickens which were tested contained the same average cellular concentration of endogenous oncornavirus DNA. In contrast, different tissues from lekemic chickens and from chickens bearing kidney tumors contained different concentrations of AMV homologous DNA: in some tissues there was no increase whereas other tissues acquired additional AMV-specific DNA sequences. The increase was the greatest in tissues which can become neoplastic after infection, such as myeloblasts, erythrocytes, and kidney cells. It was directly demonstrated that DNA from AMV-induced kidney tumor contains AMV sequences which are absent in DNA from normal cells. A similar finding had been previously obtained with leukemic cells (15). 3H-labeled 35S RNA from purified AMV was exhaustively hybridized with an excess of normal chicken DNA to remove all the viral RNA sequences which are complementary to DNA from uninfected cells. The 3H-labeled RNA which failed to hybridize was isolated by hydroxylapatite column chromatography which separates DNA-RNA hybrids from single-stranded RNA. The residual RNA hybridized to chicken kidney tumor DNA but did not rehybridize with normal chicken DNA.", "contents": "Acquisition of viral DNA sequences in target organs of chickens infected with avian myeloblastosis virus. The distribution of oncornavirus DNA sequences in various tissues of normal chickens and of chickens with leukemia or kidney tumors induced by avian myeloblastosis virus (AMV) was analyzed by DNA-RNA hybridization using 35S AMV RNA as a probe. All the tissues from normal chickens which were tested contained the same average cellular concentration of endogenous oncornavirus DNA. In contrast, different tissues from lekemic chickens and from chickens bearing kidney tumors contained different concentrations of AMV homologous DNA: in some tissues there was no increase whereas other tissues acquired additional AMV-specific DNA sequences. The increase was the greatest in tissues which can become neoplastic after infection, such as myeloblasts, erythrocytes, and kidney cells. It was directly demonstrated that DNA from AMV-induced kidney tumor contains AMV sequences which are absent in DNA from normal cells. A similar finding had been previously obtained with leukemic cells (15). 3H-labeled 35S RNA from purified AMV was exhaustively hybridized with an excess of normal chicken DNA to remove all the viral RNA sequences which are complementary to DNA from uninfected cells. The 3H-labeled RNA which failed to hybridize was isolated by hydroxylapatite column chromatography which separates DNA-RNA hybrids from single-stranded RNA. The residual RNA hybridized to chicken kidney tumor DNA but did not rehybridize with normal chicken DNA."} {"id": "PMID:170416", "title": "Transformation of primary rat kidney cells by fragments of simian virus 40 DNA.", "content": "Linear simian virus 40 (SV40) DNA molecules of genome length and DNA fragments smaller than genome length when prepared with restriction endonucleases and tested for transforming activity on primary cultures of baby rat kidney cells. The linear molecules of genome length (prepared with endonucleases R-EcoRI, R-BamHI, and R-HpaII or R-HapII), a 74% fragment (EcoRI/HpaII or HapII-A), and a 59% fragment (BamHI/HapII-A) could all transform rat kidney cells with the same efficiency as circular SV40 DNA. All transformed lines tested contained the SV40-specific T-antigen in 90 to 100% of the cells, which was taken as evidence that the transformation was SV40 specific. The DNA fragments with transforming activity contained the entire early region of SV40 DNA. Endo R-HpaI, which introduced one break in the early region, apparently inactivated the transforming capacity of SV40 DNA, since no transformation was observed with any of the three HpaI fragments tested. Attempts were made to rescue infectious virus from some of the transformed lines by fusion with permissive BSC-1 cells. Infectious virus was only recovered from the cells transformed by circular form I DNA. No infectious virus could be isolated from any of the other types of transformed cells.", "contents": "Transformation of primary rat kidney cells by fragments of simian virus 40 DNA. Linear simian virus 40 (SV40) DNA molecules of genome length and DNA fragments smaller than genome length when prepared with restriction endonucleases and tested for transforming activity on primary cultures of baby rat kidney cells. The linear molecules of genome length (prepared with endonucleases R-EcoRI, R-BamHI, and R-HpaII or R-HapII), a 74% fragment (EcoRI/HpaII or HapII-A), and a 59% fragment (BamHI/HapII-A) could all transform rat kidney cells with the same efficiency as circular SV40 DNA. All transformed lines tested contained the SV40-specific T-antigen in 90 to 100% of the cells, which was taken as evidence that the transformation was SV40 specific. The DNA fragments with transforming activity contained the entire early region of SV40 DNA. Endo R-HpaI, which introduced one break in the early region, apparently inactivated the transforming capacity of SV40 DNA, since no transformation was observed with any of the three HpaI fragments tested. Attempts were made to rescue infectious virus from some of the transformed lines by fusion with permissive BSC-1 cells. Infectious virus was only recovered from the cells transformed by circular form I DNA. No infectious virus could be isolated from any of the other types of transformed cells."} {"id": "PMID:170417", "title": "Kinetics of murine type C virus-specific DNA synthesis newly infected cells.", "content": "Replicating transforming functions of Rauscher leukemia virus (RLV) and the RLV pseudotype of Moloney sarcoma virus in mouse embryo fibroblasts were found to be most sensitive to inhibition by cytosine arabinoside (ara-C) 30 to 90 min after infection. The initiation of intracellular RLV DNA synthesis was detected by nucleic acid hybridization within this time interval. Treatment of infected cells with cytosine arabinoside abolished RLV DNA synthesis. Peak synthesis of the DNA complementary to the infecting RLV genome, the (-) strand, occurred 40 to 60 min after infection. During this interval two s two species of DNA were observed with estimated molecular weights of 0.5 X 10(5) to 1.0 X 10(5) and 3 X 10(6). Peak synthesis of the (+) strand viral DNA occurred 50 to 70 min after infection. The initial species detected had a molecular weight of 1.5 X 10(5) to 4.0 X 10(5) which shifted as a function of time to 3 X 10(6). Both (+) strand species were initially detected in the cytoplasm followed by a rapid (10-min interval) appearance of the faster-sedimenting species in the nucleus. The virus-specific (-) and (+) strand DNA species are presumably unintegrated intermediates in provirus formation.", "contents": "Kinetics of murine type C virus-specific DNA synthesis newly infected cells. Replicating transforming functions of Rauscher leukemia virus (RLV) and the RLV pseudotype of Moloney sarcoma virus in mouse embryo fibroblasts were found to be most sensitive to inhibition by cytosine arabinoside (ara-C) 30 to 90 min after infection. The initiation of intracellular RLV DNA synthesis was detected by nucleic acid hybridization within this time interval. Treatment of infected cells with cytosine arabinoside abolished RLV DNA synthesis. Peak synthesis of the DNA complementary to the infecting RLV genome, the (-) strand, occurred 40 to 60 min after infection. During this interval two s two species of DNA were observed with estimated molecular weights of 0.5 X 10(5) to 1.0 X 10(5) and 3 X 10(6). Peak synthesis of the (+) strand viral DNA occurred 50 to 70 min after infection. The initial species detected had a molecular weight of 1.5 X 10(5) to 4.0 X 10(5) which shifted as a function of time to 3 X 10(6). Both (+) strand species were initially detected in the cytoplasm followed by a rapid (10-min interval) appearance of the faster-sedimenting species in the nucleus. The virus-specific (-) and (+) strand DNA species are presumably unintegrated intermediates in provirus formation."} {"id": "PMID:170418", "title": "Size of virus-specific RNA in B-34, a hamster tumor cell producing nucleic acids of type C viruses from three species.", "content": "B-34 is the designation of a hamster tumor-derived cell line induced by the Harvey sarcoma virus. This cell line produces virions which contain structural proteins common to edogenous hamster viruses and nucleic acid sequences of hamster, mouse, and rat origin. The sedimentation characteristics of the intracellular virus-specific RNA was determined in sucrose gradients after treatment with dimethylsulfoxide by molecular hybridization using complementary DNA of strict virus specificity. Hamster virus-specific RNA sedimented at 35S (major peak) as is characteristic of productive infection by type C leukemia viruses of other species. Rat virus-specific RNA sedimented at 30S which is characteristic of the sarcoma virus-related genome found in nonproducer cells transformed by Kirsten sarcoma virus. Both Harvey and Kirsten sarcoma viruses contain a related but not necessarily identical 30S rat-specific component which is also found in normal cultured rat cells. Mouse cells producing Harvey sarcoma virus also contain a rat-specific 30S RNA. Mouse virus-derived sequences also sedimented at 30S in B-34 cells and in a similar size range in Harvey virus-infected mouse cells. The possibility that the mouse and rat-derived sequences are present on a single 30S RNA species which would then be related to sarcomagenic potential is one attractive hypothesis suggested by these data.", "contents": "Size of virus-specific RNA in B-34, a hamster tumor cell producing nucleic acids of type C viruses from three species. B-34 is the designation of a hamster tumor-derived cell line induced by the Harvey sarcoma virus. This cell line produces virions which contain structural proteins common to edogenous hamster viruses and nucleic acid sequences of hamster, mouse, and rat origin. The sedimentation characteristics of the intracellular virus-specific RNA was determined in sucrose gradients after treatment with dimethylsulfoxide by molecular hybridization using complementary DNA of strict virus specificity. Hamster virus-specific RNA sedimented at 35S (major peak) as is characteristic of productive infection by type C leukemia viruses of other species. Rat virus-specific RNA sedimented at 30S which is characteristic of the sarcoma virus-related genome found in nonproducer cells transformed by Kirsten sarcoma virus. Both Harvey and Kirsten sarcoma viruses contain a related but not necessarily identical 30S rat-specific component which is also found in normal cultured rat cells. Mouse cells producing Harvey sarcoma virus also contain a rat-specific 30S RNA. Mouse virus-derived sequences also sedimented at 30S in B-34 cells and in a similar size range in Harvey virus-infected mouse cells. The possibility that the mouse and rat-derived sequences are present on a single 30S RNA species which would then be related to sarcomagenic potential is one attractive hypothesis suggested by these data."} {"id": "PMID:170419", "title": "Murine xenotropic type C viruses I. Distribution and further characterization of the virus in NZB mice.", "content": "The xenotropic mouse type C virus, originally detected in cultured embryo cells from New Zealand Black (NZB) mice, has been recovered from over 50 adult NZB animals and 15 NZB embryos. Its presence is best detected by measuring its ability to rescue a murine sarcoma virus (MSV) genome from a non-virus-producing MSV-transformed rat cell. The virus can serve as a helper for replication of MSV. It has a distinct type-specific coat and is a prototype for a third serotype of mouse type C viruses, NZB. The xenotropic virus may have an evolutionary role since it has a wide host range, including the ability to infect avian cells. It is produced spontaneously by all cells cultivated from NZB tissues and accounts for the high concentration of viral antigens associated with NZB tissues. The extent of virus production is similar in both male and female mice. All cell clones established from embryos also produce the virus. A variability in the intracellular regulation of virus replication is suggested since tissue cells from the same animal differ quantitatively in their ability to produce xenotropic viruses. Since enhanced spontaneous virus production is associated with cells from NZB mice, the virus may play a role in the autoimmune disease of this mouse strain.", "contents": "Murine xenotropic type C viruses I. Distribution and further characterization of the virus in NZB mice. The xenotropic mouse type C virus, originally detected in cultured embryo cells from New Zealand Black (NZB) mice, has been recovered from over 50 adult NZB animals and 15 NZB embryos. Its presence is best detected by measuring its ability to rescue a murine sarcoma virus (MSV) genome from a non-virus-producing MSV-transformed rat cell. The virus can serve as a helper for replication of MSV. It has a distinct type-specific coat and is a prototype for a third serotype of mouse type C viruses, NZB. The xenotropic virus may have an evolutionary role since it has a wide host range, including the ability to infect avian cells. It is produced spontaneously by all cells cultivated from NZB tissues and accounts for the high concentration of viral antigens associated with NZB tissues. The extent of virus production is similar in both male and female mice. All cell clones established from embryos also produce the virus. A variability in the intracellular regulation of virus replication is suggested since tissue cells from the same animal differ quantitatively in their ability to produce xenotropic viruses. Since enhanced spontaneous virus production is associated with cells from NZB mice, the virus may play a role in the autoimmune disease of this mouse strain."} {"id": "PMID:170420", "title": "Sulfated components of enveloped viruses.", "content": "The glycoproteins of several enveloped viruses, grown in a variety of cell types, are labeled with 35SO4(-2), whereas the nonglycosylated proteins are not. This was shown for the HN and F glycoproteins of SV5 and Sendai virus, the E1 and E2 glycoproteins of Sindbis virus, and for the major glycoprotein, gp69, as well as for a minor glycoprotein, gp52, of Rauscher leukemia virus. The minor glycoprotein of Rauscher leukemia virus is more highly sulfated, with a ratio of 35SO4- [3H]glucosamine about threefold greater than that of gp69. The G protein of vesicular stomatitis virus was labeled when virions were grown in the MDBK line of bovine kidney cells, although no significant incorporation of 35SO4(-2) into this protein was observed in virions grown in BHK21-F line of baby hamster kidney cells. In addition to the viral glycoproteins, sulfate was also incorporated into a heterogenous component with an electrophoretic mobility lower than that of any labeled with 35SO4(-2) and [3H]leucine, this component had a much greater 35S-3H ratio than any of the viral polypeptides and thus could not represent aggregated viral proteins. This material is believed to be a cell-derived mucopolysaccharide and can be removed from virions by treatment with hyaluronidase without affecting the amount of sulfate present on the glycoproteins.", "contents": "Sulfated components of enveloped viruses. The glycoproteins of several enveloped viruses, grown in a variety of cell types, are labeled with 35SO4(-2), whereas the nonglycosylated proteins are not. This was shown for the HN and F glycoproteins of SV5 and Sendai virus, the E1 and E2 glycoproteins of Sindbis virus, and for the major glycoprotein, gp69, as well as for a minor glycoprotein, gp52, of Rauscher leukemia virus. The minor glycoprotein of Rauscher leukemia virus is more highly sulfated, with a ratio of 35SO4- [3H]glucosamine about threefold greater than that of gp69. The G protein of vesicular stomatitis virus was labeled when virions were grown in the MDBK line of bovine kidney cells, although no significant incorporation of 35SO4(-2) into this protein was observed in virions grown in BHK21-F line of baby hamster kidney cells. In addition to the viral glycoproteins, sulfate was also incorporated into a heterogenous component with an electrophoretic mobility lower than that of any labeled with 35SO4(-2) and [3H]leucine, this component had a much greater 35S-3H ratio than any of the viral polypeptides and thus could not represent aggregated viral proteins. This material is believed to be a cell-derived mucopolysaccharide and can be removed from virions by treatment with hyaluronidase without affecting the amount of sulfate present on the glycoproteins."} {"id": "PMID:170421", "title": "Simian virus 40 integration sites in the genome of virus-transformed mouse cells.", "content": "To gain information on the specificity of simian virus 40 (SV40) integration in the genome of transformed cells, mouse 3T3 cells were transformed by a temperature-sensitive (ts) SV40 mutant, using high multiplicity of infection (MOI). Transformed cells were superinfected with wild-type (wt) virus at high MOI. Clones were isolated and fused with permissive BSC-1 cells to promote virus rescue. All rescued viruses were of the ts type only. When the high-MOI transformants were infected with 3H-labeled wt SV40, the amount of radioactivity associated with their nuclear fraction was found to be similar to that of 3T3 cells. 3T3 cells were then transformed by ts SV40 at low MOI and superinfected by wt virus at high MOI. Upon fusion with BSC-1 cells, most clones produced both ts and wt virus. These results suggest that the number of stable SV40 integration sites in the 3T3 genome is limited, since they can be saturated by transformation at high MOI. When the MOI is low, the sites are not saturated and a subsequent infection can lead to integration.", "contents": "Simian virus 40 integration sites in the genome of virus-transformed mouse cells. To gain information on the specificity of simian virus 40 (SV40) integration in the genome of transformed cells, mouse 3T3 cells were transformed by a temperature-sensitive (ts) SV40 mutant, using high multiplicity of infection (MOI). Transformed cells were superinfected with wild-type (wt) virus at high MOI. Clones were isolated and fused with permissive BSC-1 cells to promote virus rescue. All rescued viruses were of the ts type only. When the high-MOI transformants were infected with 3H-labeled wt SV40, the amount of radioactivity associated with their nuclear fraction was found to be similar to that of 3T3 cells. 3T3 cells were then transformed by ts SV40 at low MOI and superinfected by wt virus at high MOI. Upon fusion with BSC-1 cells, most clones produced both ts and wt virus. These results suggest that the number of stable SV40 integration sites in the 3T3 genome is limited, since they can be saturated by transformation at high MOI. When the MOI is low, the sites are not saturated and a subsequent infection can lead to integration."} {"id": "PMID:170422", "title": "Morphogenesis of Sindbis virus in cultured Aedes albopictus cells.", "content": "Cultured mosquito cells were found to produce Sindbis virus nearly as efficiently as BHK-21 cells at 28 C. In virtually all of the cells observed in the electron microscope, virus morphogenesis was found to occur within complex vesicular structures which developed after viral infection. Viral nucleocapsids were first seen in these vesicles and appeared to be enveloped within these structures. The process of envelopment within these inclusions differed in some respects from the process previously described for the envelopment of nucleocapsids at the plasma membrane of vertebrae cells. Free nucleocapsids were only rarely seen in the cytoplasm of infected mosquito cells, and budding of virus from the cell surface was detected so infrequently that this process of virus production could not account for the amount of virus produced by the infected cells. The vast majority of extracellular virus was produced by the fusion of the virus-containing vesicles with the plasma membrane releasing mature virions and membrane nucleocapsid complexes in various stages of development.", "contents": "Morphogenesis of Sindbis virus in cultured Aedes albopictus cells. Cultured mosquito cells were found to produce Sindbis virus nearly as efficiently as BHK-21 cells at 28 C. In virtually all of the cells observed in the electron microscope, virus morphogenesis was found to occur within complex vesicular structures which developed after viral infection. Viral nucleocapsids were first seen in these vesicles and appeared to be enveloped within these structures. The process of envelopment within these inclusions differed in some respects from the process previously described for the envelopment of nucleocapsids at the plasma membrane of vertebrae cells. Free nucleocapsids were only rarely seen in the cytoplasm of infected mosquito cells, and budding of virus from the cell surface was detected so infrequently that this process of virus production could not account for the amount of virus produced by the infected cells. The vast majority of extracellular virus was produced by the fusion of the virus-containing vesicles with the plasma membrane releasing mature virions and membrane nucleocapsid complexes in various stages of development."} {"id": "PMID:170423", "title": "Virion trascriptase activity differences in host range mutants of vesicular stomatitis virus.", "content": "Three types of conditional lethal mutant were isolated from wild-type vesicular stomatitis virus, New Jersey serotype, after mutagenization by 5-fluorouracil: (i) conventional temperature-sensitive (ts) mutants, which form plaques at 31 C but not at 39 C; (ii) conventional host range mutants (hr CE), which grow in BHK but not in secondary chicken embryo cells; and (iii) temperature-dependent host range mutants (td CE), which form plaques both at 31 and 39 C on BHK cells but only at 31 C on chicken embryo cells. To determine whether the mutation in hr CE and td CE mutants affected the virion-associated RNA transcriptase, this enzyme was assayed in vitro at 31 and 39 C, and the results were compared with those obtained for the wild-type virus. The RNA trascriptase activity of hr CE mutants did not appear to be affected by the mutation. The td CE mutants fall into two classes: those that synthesized RNA at 39 C similar to the wild-type virus and those that did not. One mutant of the latter category, td CE 3, had heat-sensitive transcriptase regardless of whether it was grown in BHK or chicken embryo cells. A revertant to the wild-type phenotype isolated from this mutant had regained the ability to synthesize RNA at 39 C. These results strongly suggest that a polypeptide that is either the transcriptase itself or part of the transcriptase complex was made temperature sensitive by the mutation in the second class of td CE mutants. The inhibition of the transcriptase activity of the mutant td CE 3 was fully reversible by lowering the temperature of incubation from 39 to 31 C, and both inhibition and reactivation appeared to be instantaneous.", "contents": "Virion trascriptase activity differences in host range mutants of vesicular stomatitis virus. Three types of conditional lethal mutant were isolated from wild-type vesicular stomatitis virus, New Jersey serotype, after mutagenization by 5-fluorouracil: (i) conventional temperature-sensitive (ts) mutants, which form plaques at 31 C but not at 39 C; (ii) conventional host range mutants (hr CE), which grow in BHK but not in secondary chicken embryo cells; and (iii) temperature-dependent host range mutants (td CE), which form plaques both at 31 and 39 C on BHK cells but only at 31 C on chicken embryo cells. To determine whether the mutation in hr CE and td CE mutants affected the virion-associated RNA transcriptase, this enzyme was assayed in vitro at 31 and 39 C, and the results were compared with those obtained for the wild-type virus. The RNA trascriptase activity of hr CE mutants did not appear to be affected by the mutation. The td CE mutants fall into two classes: those that synthesized RNA at 39 C similar to the wild-type virus and those that did not. One mutant of the latter category, td CE 3, had heat-sensitive transcriptase regardless of whether it was grown in BHK or chicken embryo cells. A revertant to the wild-type phenotype isolated from this mutant had regained the ability to synthesize RNA at 39 C. These results strongly suggest that a polypeptide that is either the transcriptase itself or part of the transcriptase complex was made temperature sensitive by the mutation in the second class of td CE mutants. The inhibition of the transcriptase activity of the mutant td CE 3 was fully reversible by lowering the temperature of incubation from 39 to 31 C, and both inhibition and reactivation appeared to be instantaneous."} {"id": "PMID:170424", "title": "Virus-induced proteins in pseudorabies-infected cells. II. Proteins of the virion and nucleocapsid.", "content": "Analysis of purified naked and enveloped nucleocapsids of pseudorabies virus with high-resolution techniques has allowed a reassessment of their protein composition. Enveloped particles are shown to contain at least 20 proteins whose molecular weights are in the range 20,000 to 230,000. Naked nucleocapsids contain one major and seven minor proteins in the molecular weight range 20,000 to 155,000. Phosphorylation of at least one virion protein is shown to take place in vivo. These results demonstrate that pseudorabies virus is similar in its protein complement to other herpesviruses which have recently been examined.", "contents": "Virus-induced proteins in pseudorabies-infected cells. II. Proteins of the virion and nucleocapsid. Analysis of purified naked and enveloped nucleocapsids of pseudorabies virus with high-resolution techniques has allowed a reassessment of their protein composition. Enveloped particles are shown to contain at least 20 proteins whose molecular weights are in the range 20,000 to 230,000. Naked nucleocapsids contain one major and seven minor proteins in the molecular weight range 20,000 to 155,000. Phosphorylation of at least one virion protein is shown to take place in vivo. These results demonstrate that pseudorabies virus is similar in its protein complement to other herpesviruses which have recently been examined."} {"id": "PMID:170425", "title": "Physical map of the BK virus genome.", "content": "Two new human papovavirus isolates (JMV and MMV) from the urines of patients with Wiskott-Aldrich syndrome were morphologically and serologically identical to BK virus (BKV). The genomes of these two new isolates were found to be indistinguishable from prototype BKV DNA in a variety of nucleic acid hybridization experiments. Like BKV DNA, JMV and MMV DNAs share approximately 20% of their polynucleotide sequences with simian virus 40 DNA. The genome of JMV was indistinguishable from that of BKV by restriction endonuclease analysis; MMV DNA contained three instead of four R-Hind cleavage sites and one rather than no R-HpaII cleavage sites. Physical maps of the BKV and MMV genomes were constructed using restriction endonucleases, and these maps were oriented to the map of simian virus 40 DNA.", "contents": "Physical map of the BK virus genome. Two new human papovavirus isolates (JMV and MMV) from the urines of patients with Wiskott-Aldrich syndrome were morphologically and serologically identical to BK virus (BKV). The genomes of these two new isolates were found to be indistinguishable from prototype BKV DNA in a variety of nucleic acid hybridization experiments. Like BKV DNA, JMV and MMV DNAs share approximately 20% of their polynucleotide sequences with simian virus 40 DNA. The genome of JMV was indistinguishable from that of BKV by restriction endonuclease analysis; MMV DNA contained three instead of four R-Hind cleavage sites and one rather than no R-HpaII cleavage sites. Physical maps of the BKV and MMV genomes were constructed using restriction endonucleases, and these maps were oriented to the map of simian virus 40 DNA."} {"id": "PMID:170426", "title": "Long-term persistence of cytomegalovirus genome in cultured human cells of prostatic origin.", "content": "Cells from prostatic tissue obtained from a 3-year-old male donor exhibited scattered foci of cytopathology on primary culture. A virus was isolated and shown by serological analysis to be cytomegalovirus (CMV). After a number of cell culture passages, a cell line (disignated CMV-Mj-P) was obtained in which foci of infection could no longer be demonstrated, nor could virus be rescued. On continued passage the doubling time of the cells decreased markedly, and the fibroblastoid cells ceased to demonstrate contact inhibition. CMV-specific antigen(s) was detected on the surface of the cells by indirect immunofluorescence techniques after exposure of the cultures to iododeoxyuridine. Microcytotoxocity tests established that CMV-Mj-P cells, but not control human prostate cells or human embryonic lung cells, share a membrane antigen with hamster cells transformed by CMV. Nucleic acid hybridization studies revealed that virus genetic information was carried by the human prostate cells and that the cells contained an average of about 10 to 15 genome equivalents of CMV DNA. Karyotypic analysis confirmed that the CMV-Mj-P cells were of human male origin. These results indicate that the cells either have been transformed by CMV or are chronically infected with CMV and releasing virus at levels below detection.", "contents": "Long-term persistence of cytomegalovirus genome in cultured human cells of prostatic origin. Cells from prostatic tissue obtained from a 3-year-old male donor exhibited scattered foci of cytopathology on primary culture. A virus was isolated and shown by serological analysis to be cytomegalovirus (CMV). After a number of cell culture passages, a cell line (disignated CMV-Mj-P) was obtained in which foci of infection could no longer be demonstrated, nor could virus be rescued. On continued passage the doubling time of the cells decreased markedly, and the fibroblastoid cells ceased to demonstrate contact inhibition. CMV-specific antigen(s) was detected on the surface of the cells by indirect immunofluorescence techniques after exposure of the cultures to iododeoxyuridine. Microcytotoxocity tests established that CMV-Mj-P cells, but not control human prostate cells or human embryonic lung cells, share a membrane antigen with hamster cells transformed by CMV. Nucleic acid hybridization studies revealed that virus genetic information was carried by the human prostate cells and that the cells contained an average of about 10 to 15 genome equivalents of CMV DNA. Karyotypic analysis confirmed that the CMV-Mj-P cells were of human male origin. These results indicate that the cells either have been transformed by CMV or are chronically infected with CMV and releasing virus at levels below detection."} {"id": "PMID:170430", "title": "Brachial plexus neuropathy. Association with desensitizing antiallergy injections.", "content": "Two patients had acute, self-limiting, unilateral brachial plexus neuropathy in association with desensitizing subcutaneous injections of extracts of dusts and molds. Diminution of pain and return of function of the affected limb followed a short course of prednisone therapy, although a beneficial effect of the steroid cannot be considered proved. There is a large variety of antigenic substances already known to produce neuropathy following intramuscular injection; desensitizing antiallergy injections should be added to this list.", "contents": "Brachial plexus neuropathy. Association with desensitizing antiallergy injections. Two patients had acute, self-limiting, unilateral brachial plexus neuropathy in association with desensitizing subcutaneous injections of extracts of dusts and molds. Diminution of pain and return of function of the affected limb followed a short course of prednisone therapy, although a beneficial effect of the steroid cannot be considered proved. There is a large variety of antigenic substances already known to produce neuropathy following intramuscular injection; desensitizing antiallergy injections should be added to this list."} {"id": "PMID:170442", "title": "Studies on rat complement. II. Complement level in experimental tumor in rats.", "content": "In the course of methylcholanthrene induced carcinogenesis in rats, CIA50, C4 and C3 increased as compared with control and correlation of tumor size with increase in CIA50, C4 and C3 was observed. In the course of dimethylaminoazobenzen carcinogenesis of rats, complement level and C3 level decreased but in splenectomized rats fed by dimethylaminoazobenzen showed elevated level of complement system. After Corynebacterium infection, CIA50 and C3 of rats increased. This phenomenon is considered to be one of the essential factors to induce high resistance against tumor inoculation.", "contents": "Studies on rat complement. II. Complement level in experimental tumor in rats. In the course of methylcholanthrene induced carcinogenesis in rats, CIA50, C4 and C3 increased as compared with control and correlation of tumor size with increase in CIA50, C4 and C3 was observed. In the course of dimethylaminoazobenzen carcinogenesis of rats, complement level and C3 level decreased but in splenectomized rats fed by dimethylaminoazobenzen showed elevated level of complement system. After Corynebacterium infection, CIA50 and C3 of rats increased. This phenomenon is considered to be one of the essential factors to induce high resistance against tumor inoculation."} {"id": "PMID:170444", "title": "Neutralizing activities of early and late IgG fragments from rabbits immunized with herpes simplex virus.", "content": "Rabbits immunized with herpes virus were bled periodically and bivalent and univalent fragments of IgG from each serum sample were prepared by enzymatic digestion. The 2-week F(ab')2 showed a low neutralizing activity only after addition of anti-IgG. F(ab')2 of the 4-week serum retained almost all of the neutralizing activity of IgG, while its univalent fragments demonstrated none even when tested with anti-IgG. In contrast to these early IgG fragments, univalent fragments of the 9-week and 20-week IgG neutralized the virus to considerable extents in the absence of anti-IgG; after addition of anti-IgG the activity equaled that of intact IgG in the cases of Fab' and Fab-II, though the activity of Fab-I was relatively low. Three three univalent fragments were all sensitive to heating at 70 C and to ultraviolet irradiation, whereas intact IgG resisted these treatments. F(ab')2 was resistant to the heating and less sensitive to ultraviolet irradiation than univalent fragments. Neutralization kinetic curve experiments to test blocking effects of IgG fragments against the neutralization by intact IgG suggested that the early Fab' did combine with the virus and that the late Fab' exerted a higher blocking effect than the early Fab'.", "contents": "Neutralizing activities of early and late IgG fragments from rabbits immunized with herpes simplex virus. Rabbits immunized with herpes virus were bled periodically and bivalent and univalent fragments of IgG from each serum sample were prepared by enzymatic digestion. The 2-week F(ab')2 showed a low neutralizing activity only after addition of anti-IgG. F(ab')2 of the 4-week serum retained almost all of the neutralizing activity of IgG, while its univalent fragments demonstrated none even when tested with anti-IgG. In contrast to these early IgG fragments, univalent fragments of the 9-week and 20-week IgG neutralized the virus to considerable extents in the absence of anti-IgG; after addition of anti-IgG the activity equaled that of intact IgG in the cases of Fab' and Fab-II, though the activity of Fab-I was relatively low. Three three univalent fragments were all sensitive to heating at 70 C and to ultraviolet irradiation, whereas intact IgG resisted these treatments. F(ab')2 was resistant to the heating and less sensitive to ultraviolet irradiation than univalent fragments. Neutralization kinetic curve experiments to test blocking effects of IgG fragments against the neutralization by intact IgG suggested that the early Fab' did combine with the virus and that the late Fab' exerted a higher blocking effect than the early Fab'."} {"id": "PMID:170446", "title": "Synaptic organization in teleost spinal motoneurons.", "content": "Glass microelectrodes were inserted into motoneurons innervating pectoral fin muscles to record action and synaptic potentials, evoked by electrical stimulation of ventral and dorsal roots, and the medulla oblongata. Ventral root stimulation evoked a small depolarizing response which had properties compatible with those of the EPSP; its amplitude changes were graded, being increased by membrane hyperpolarization and decreased by high frequency repetitive stimulation. The latency of the response was sufficiently longer than that of the antidromic spike to allow for a monosynaptic delay. Stimulation of the dorsal root produced EPSPs with relatively long latencies, suggesting mediation by a polysynaptic pathway. EPSPs with short latencies were evoked by stimulation of the medulla oblongata, indicating the presence of a monosynaptic excitatory connection. Action potentials, recorded from peripheral nerve after stimulation of the medulla oblongata, were facilitated by conditioning volleys via ventral roots. This facilitation was blocked by dihydro-beta-erythroidine hydrobromide and atropine sulphate, indicating the cholinergic nature of the EPSP of ventral root origin. The conduction velocities of motor axons and of the ventral roots fibers responsible for production of EPSPs were about the same. The EPSP of ventral root origin had a slower rising time course and lesser sensitivity to shifts of membrane potential than the EPSP of medulla oblongata origin, suggesting that the sites of generation of the former EPSP were on the peripheral dendrites. From the above results, it was concluded that the EPSP of ventral root origin was mediated by recurrent axon collaterals of motoneurons.", "contents": "Synaptic organization in teleost spinal motoneurons. Glass microelectrodes were inserted into motoneurons innervating pectoral fin muscles to record action and synaptic potentials, evoked by electrical stimulation of ventral and dorsal roots, and the medulla oblongata. Ventral root stimulation evoked a small depolarizing response which had properties compatible with those of the EPSP; its amplitude changes were graded, being increased by membrane hyperpolarization and decreased by high frequency repetitive stimulation. The latency of the response was sufficiently longer than that of the antidromic spike to allow for a monosynaptic delay. Stimulation of the dorsal root produced EPSPs with relatively long latencies, suggesting mediation by a polysynaptic pathway. EPSPs with short latencies were evoked by stimulation of the medulla oblongata, indicating the presence of a monosynaptic excitatory connection. Action potentials, recorded from peripheral nerve after stimulation of the medulla oblongata, were facilitated by conditioning volleys via ventral roots. This facilitation was blocked by dihydro-beta-erythroidine hydrobromide and atropine sulphate, indicating the cholinergic nature of the EPSP of ventral root origin. The conduction velocities of motor axons and of the ventral roots fibers responsible for production of EPSPs were about the same. The EPSP of ventral root origin had a slower rising time course and lesser sensitivity to shifts of membrane potential than the EPSP of medulla oblongata origin, suggesting that the sites of generation of the former EPSP were on the peripheral dendrites. From the above results, it was concluded that the EPSP of ventral root origin was mediated by recurrent axon collaterals of motoneurons."} {"id": "PMID:170447", "title": "Two preferential conducting pathways within the bundle of His of the dog heart.", "content": "An isolated preparation formed exclusively of the specific conducting tissue of the A. V. node, bundle of His and bundle branches was dissected from the dog heart and studied using the microelectrode technique. The preparation, being completely isolated from the normal neighboring conducting tissues, can be turned over or twisted, so as to stimulate and record either separately or simultaneously the electrical activity of the dorsal and ventral surfaces of the bundle of His. The preparation showed spontaneous activity and maintained its physiological properties for long periods of time. Morphological and electrophysiological evidence was found to differentiate two functional strands within the common trunk of the bundle of His. These two strands appear in different planes: The anterior or ventral strand starts in the superior part of the atrioventricular node and continues to form the right bundle branch; the posterior or dorsal strand begins in the inferior part of the A. V. node and runs underneath the ventral strand to form later the left bundle branch. The two strands can be separated from each other so as to have two functional preparations: one formed of the superior part of the A. V. node, the anterior strand and the right bundle branch; the other constituted by the inferior part of the A. V. node, the posterior strand and the left bundle branch. Some of the electrophysiological properties of both strands are similar, except for the conduction velocity, which appears to be faster in the posterior strand than in the anterior. Transversal propagation occurs between the two strands and is slower than the longitudinal propagation that takes place along the parallel fibers of each strand. The presence of cellular transversal bridges between the strands assures the activation of the two strands as if they were a single conducting cable. These characteristics are discussed in relation to some disturbances in propagation.", "contents": "Two preferential conducting pathways within the bundle of His of the dog heart. An isolated preparation formed exclusively of the specific conducting tissue of the A. V. node, bundle of His and bundle branches was dissected from the dog heart and studied using the microelectrode technique. The preparation, being completely isolated from the normal neighboring conducting tissues, can be turned over or twisted, so as to stimulate and record either separately or simultaneously the electrical activity of the dorsal and ventral surfaces of the bundle of His. The preparation showed spontaneous activity and maintained its physiological properties for long periods of time. Morphological and electrophysiological evidence was found to differentiate two functional strands within the common trunk of the bundle of His. These two strands appear in different planes: The anterior or ventral strand starts in the superior part of the atrioventricular node and continues to form the right bundle branch; the posterior or dorsal strand begins in the inferior part of the A. V. node and runs underneath the ventral strand to form later the left bundle branch. The two strands can be separated from each other so as to have two functional preparations: one formed of the superior part of the A. V. node, the anterior strand and the right bundle branch; the other constituted by the inferior part of the A. V. node, the posterior strand and the left bundle branch. Some of the electrophysiological properties of both strands are similar, except for the conduction velocity, which appears to be faster in the posterior strand than in the anterior. Transversal propagation occurs between the two strands and is slower than the longitudinal propagation that takes place along the parallel fibers of each strand. The presence of cellular transversal bridges between the strands assures the activation of the two strands as if they were a single conducting cable. These characteristics are discussed in relation to some disturbances in propagation."} {"id": "PMID:170448", "title": "Effects of jaundiced plasma on vascular sensitivity to noradrenalin.", "content": "Alterations in renal perfusion have been shown in a variety of liver diseases. We have examined the possibility that the syndrome is due to a renal vascular hypersensitivity to noradrenalin (NA). Isolated perfused kidneys and segments of rabbit femoral artery were used. Potentiation of the pressor effects of injected NA occurred in all (five artery and five kidney) preparations when jaundiced baboon plasma was perfused. These changes were significant (P less than 0.05) in nine out of the ten experiments. Controls to which normal baboon plasma was administered showed no such change. No correlation was found between the degree of NA potentiation and the plasma concentrations of bilirubin (total and conjugated), serum glutamic oxaloacetic transaminase, blood urea nitrogen, serum glutamic pyruvic transaminase, alkaline phosphatase, Na+ ions or K+ ions in the jaundiced plasma. Plasma renin levels were not significantly changed. When arteris were perfused with Krebtentiation of NA was found. Perfusion of sodium taurocholate or sodium deoxycholate (400 mug/ml) yielded no potentiation. Thus, the altered renal perfusion associated with jaundice may be attributed to a potentiated pressor response to NA which may be caused by an increased level of cholesterol carried on the beta-lipoprotein.", "contents": "Effects of jaundiced plasma on vascular sensitivity to noradrenalin. Alterations in renal perfusion have been shown in a variety of liver diseases. We have examined the possibility that the syndrome is due to a renal vascular hypersensitivity to noradrenalin (NA). Isolated perfused kidneys and segments of rabbit femoral artery were used. Potentiation of the pressor effects of injected NA occurred in all (five artery and five kidney) preparations when jaundiced baboon plasma was perfused. These changes were significant (P less than 0.05) in nine out of the ten experiments. Controls to which normal baboon plasma was administered showed no such change. No correlation was found between the degree of NA potentiation and the plasma concentrations of bilirubin (total and conjugated), serum glutamic oxaloacetic transaminase, blood urea nitrogen, serum glutamic pyruvic transaminase, alkaline phosphatase, Na+ ions or K+ ions in the jaundiced plasma. Plasma renin levels were not significantly changed. When arteris were perfused with Krebtentiation of NA was found. Perfusion of sodium taurocholate or sodium deoxycholate (400 mug/ml) yielded no potentiation. Thus, the altered renal perfusion associated with jaundice may be attributed to a potentiated pressor response to NA which may be caused by an increased level of cholesterol carried on the beta-lipoprotein."} {"id": "PMID:170450", "title": "[Elimination and excretion of adenylate kinases following cell damage].", "content": "Adenylate kinases, small organ-specific isoenzymes which appear after tissue damage in the blood plasma are partly eliminated via the kidney. After intravenous administration of 3000 enzyme units of 14C-labelled adenylate kinase to rats, about 50% of the enzyme and of the radioactivity are found in the urine within 7 minutes. The elimination of adenylate kinase from the serum occurs in two phases, a faster (half-life 16 minutes) and a slower (half-life 160 minutes). After intravenous adminstration of adenylate kinase to humans, a part of the activity was recovered in the urine within minutes. The potential use of assaying adenylate kinase levels for early diagnosis of myocardial infarction is discussed. Using various skeletal muscle diseases as examples, the possible use of the very rapid elimination of adenylate kinase from the serum in monitoring the course of the acute illnesses is described. The competitive inhibitor diadenosine pentaphosphate (AP5A) has a much higher affinity for the adenylate kinases from erythrocytes, heart or skeletal muscle than for the isoenzymes from liver or kidney. Therefore, AP5A can be used for the differential determination of adenylate kinase isoenzymes in the blood plasma or the urine.", "contents": "[Elimination and excretion of adenylate kinases following cell damage]. Adenylate kinases, small organ-specific isoenzymes which appear after tissue damage in the blood plasma are partly eliminated via the kidney. After intravenous administration of 3000 enzyme units of 14C-labelled adenylate kinase to rats, about 50% of the enzyme and of the radioactivity are found in the urine within 7 minutes. The elimination of adenylate kinase from the serum occurs in two phases, a faster (half-life 16 minutes) and a slower (half-life 160 minutes). After intravenous adminstration of adenylate kinase to humans, a part of the activity was recovered in the urine within minutes. The potential use of assaying adenylate kinase levels for early diagnosis of myocardial infarction is discussed. Using various skeletal muscle diseases as examples, the possible use of the very rapid elimination of adenylate kinase from the serum in monitoring the course of the acute illnesses is described. The competitive inhibitor diadenosine pentaphosphate (AP5A) has a much higher affinity for the adenylate kinases from erythrocytes, heart or skeletal muscle than for the isoenzymes from liver or kidney. Therefore, AP5A can be used for the differential determination of adenylate kinase isoenzymes in the blood plasma or the urine."} {"id": "PMID:170451", "title": "Plasma glycosphingolipids in diabetics and normals.", "content": "In diabetic patients with hyperlipoproteinemia type IV the monohexosyl ceramide concentration in blood plasma is significantly elevated. This augmentation can be attributed to an increased monohexosyl ceramide content of the BLDL plasma fraction. In contrast, the di-, tri-, the tetrahexosyl ceramide levels remain within normal limits. In normolipidemic diabetics of comparable age, sex, and weight classes and of comparable metabolic control no elevations of glycolipid fractions could be found. However, patients with primary hyperlipoproteinemia type IV show an increase of monohexosyl ceramide concentrations in blood plasma. Therefore, the augmentation of monohexosyl ceramide levels in plasma of hyperlipidemic diabetic patients seems rather a metabolic consequence of hyperlipoproteinemia than of diabetes per se. A clearcut explantation for the monohexosyl ceramide elevations in the studied groups cannot be given at present time.", "contents": "Plasma glycosphingolipids in diabetics and normals. In diabetic patients with hyperlipoproteinemia type IV the monohexosyl ceramide concentration in blood plasma is significantly elevated. This augmentation can be attributed to an increased monohexosyl ceramide content of the BLDL plasma fraction. In contrast, the di-, tri-, the tetrahexosyl ceramide levels remain within normal limits. In normolipidemic diabetics of comparable age, sex, and weight classes and of comparable metabolic control no elevations of glycolipid fractions could be found. However, patients with primary hyperlipoproteinemia type IV show an increase of monohexosyl ceramide concentrations in blood plasma. Therefore, the augmentation of monohexosyl ceramide levels in plasma of hyperlipidemic diabetic patients seems rather a metabolic consequence of hyperlipoproteinemia than of diabetes per se. A clearcut explantation for the monohexosyl ceramide elevations in the studied groups cannot be given at present time."} {"id": "PMID:170480", "title": "Inhibition of melanoma growth in hamsters by type-2 adenovirus.", "content": "Type-2 adenovirus was shown to inhibit the growth of transplantable hamster melanoma in 70% of Syrian hamsters without any injurious effect to the host. Greatest inhibition of tumor formation was seen when animals were injected with 10(6) TCD50 of adenovirus and 2.5 x 10(5) tumor cells, or 10(6) TCD50 of virus and 5.0 x 10(5) tumor cells followed either 1 or 7 days later by a second injection of a similar dose of virus. Significant inhibition in tumor growth was also noted when 2 injections of virus (10(6.2) TCD50/injection) were given on 2 separate occasions as late as 7 and 10 days after the inoculation of tumor cells. The mechanism of tumor inhibition is not known but it could be due to a combination of factors such as viral toxicity, viral oncolysis, and antitumor immunity.", "contents": "Inhibition of melanoma growth in hamsters by type-2 adenovirus. Type-2 adenovirus was shown to inhibit the growth of transplantable hamster melanoma in 70% of Syrian hamsters without any injurious effect to the host. Greatest inhibition of tumor formation was seen when animals were injected with 10(6) TCD50 of adenovirus and 2.5 x 10(5) tumor cells, or 10(6) TCD50 of virus and 5.0 x 10(5) tumor cells followed either 1 or 7 days later by a second injection of a similar dose of virus. Significant inhibition in tumor growth was also noted when 2 injections of virus (10(6.2) TCD50/injection) were given on 2 separate occasions as late as 7 and 10 days after the inoculation of tumor cells. The mechanism of tumor inhibition is not known but it could be due to a combination of factors such as viral toxicity, viral oncolysis, and antitumor immunity."} {"id": "PMID:170481", "title": "Long-term survival in bronchogenic carcinoma.", "content": "In this report, we shall review the clinical and pathological features of 64 patients who survived 10 years or longer after resection for bronchogenic carcinoma. Most of these patients had either adenocarcinoma or bronchioloalveolar carcinoma. None of them had oat cell carcinoma. In many of the long-term survivors, there were pathological findings generally considered to indicate a poor chance for survival. Thus we believe that curative resection for bronchogenic carcinoma should be attempted whenever feasible to offer the patient every hope of long-term survival.", "contents": "Long-term survival in bronchogenic carcinoma. In this report, we shall review the clinical and pathological features of 64 patients who survived 10 years or longer after resection for bronchogenic carcinoma. Most of these patients had either adenocarcinoma or bronchioloalveolar carcinoma. None of them had oat cell carcinoma. In many of the long-term survivors, there were pathological findings generally considered to indicate a poor chance for survival. Thus we believe that curative resection for bronchogenic carcinoma should be attempted whenever feasible to offer the patient every hope of long-term survival."} {"id": "PMID:170482", "title": "Multiple primary lung cancers.", "content": "Data on 50 patients with multiple separate primary carcinomas of the lung are presented. Eighteen had synchronous tumors and 32 had metachronous tumors, the intervals between diagnoses varying from 4 months to 16 years. Histologic patterns in the two different carcinomas were the same in 31 patients, most commonly epidermoid, and they were different in 19 patients. The problems involved in establishing the diagnosis of multiple primary lung cancers, the choice of treatment, and the expectation for survival are discussed.", "contents": "Multiple primary lung cancers. Data on 50 patients with multiple separate primary carcinomas of the lung are presented. Eighteen had synchronous tumors and 32 had metachronous tumors, the intervals between diagnoses varying from 4 months to 16 years. Histologic patterns in the two different carcinomas were the same in 31 patients, most commonly epidermoid, and they were different in 19 patients. The problems involved in establishing the diagnosis of multiple primary lung cancers, the choice of treatment, and the expectation for survival are discussed."} {"id": "PMID:170488", "title": "Effects of structural variation in beta-monoglycerides and other lipids on ordering in synthetic membranes.", "content": "Studies of beta-monoglyceride multilayers were carried out using a variety of spin probes. Effects of variables such as chain length, unsaturation, and branching on organization of acyl chains in lipids of model membranes were assessed. In addition, effects of added cholesterol on membrane order were determined. Results indicated that pure beta-monolaurin yields highly ordered films, whereas, unsaturated glycerides such as beta-monoolein, beta-monolinolein, and analogous lecithins yield fluid films. Branched monoglycerides behaved similarly to beta-monoolein, suggesting that branching in acyl chains is an effective substitute for unsaturation in maintaining membrane integrity. Multilayers of beta-monoglycerides exhibited similar properties to those of more complex lipids such as phospholipids. beta-Monoglycerides, by virtue of the presence of a single acyl chain, provided a relatively simple and effective alternative to the use of phospholipids in studies of membrane architecture.", "contents": "Effects of structural variation in beta-monoglycerides and other lipids on ordering in synthetic membranes. Studies of beta-monoglyceride multilayers were carried out using a variety of spin probes. Effects of variables such as chain length, unsaturation, and branching on organization of acyl chains in lipids of model membranes were assessed. In addition, effects of added cholesterol on membrane order were determined. Results indicated that pure beta-monolaurin yields highly ordered films, whereas, unsaturated glycerides such as beta-monoolein, beta-monolinolein, and analogous lecithins yield fluid films. Branched monoglycerides behaved similarly to beta-monoolein, suggesting that branching in acyl chains is an effective substitute for unsaturation in maintaining membrane integrity. Multilayers of beta-monoglycerides exhibited similar properties to those of more complex lipids such as phospholipids. beta-Monoglycerides, by virtue of the presence of a single acyl chain, provided a relatively simple and effective alternative to the use of phospholipids in studies of membrane architecture."} {"id": "PMID:170489", "title": "Lipids of cultured hepatoma cells: VII. Structural analyses of glycerolipids in minimal deviation hepatoma 7288C.", "content": "Phosphatidylcholine. phosphatidylethanolamine, and triglycerides were isolated from minimal deviation hepatoma 7288C cells cultured as monolayers to confluency in roller flasks containing Swim's 77 medium supplemented with 5% fetal calf serum, plus 20%, 10%, or 5% bovine serum. Fatty acid distribution at each position of glycerol was determined for the 3 glycerolipid classes, and carbon number distributions of triglycerides and diglycerides derived from phosphatidylcholine and phosphatidylethanolamine were quantitated by high temperature gas liquid chromatography. Fatty acid composition was only marginally affected by the level of bovine serum in the culture medium. Percentage composition of fatty acids esterified at each position of the 3 glycerolipids was different, indicating a nonrandom distribution of acyl groups in triglycerides and the 2 diacyl phosphatides. The carbon number distribution of diglycerides derived from phosphatidylcholine and phosphatidylethanolamine was different, and neither carbon number distribution agreed with the calculated 1-random, 2-random diacyl distribution, thus indicating pairing of certain acids in the diglycerides derived from these phospholipd classes. The determined triglyceride carbon number distributions did not show complete agreement with those calculated, assuming a 1-random, 2-random, 3-random type of fatty acyl distribution, suggesting preferential pairing of some acids in this lipid class. The 1-, 2-diglycerides derived from phosphatidylcholine, phosphatidylethanolamine, and triglycerides differed, indicating either selectivity in utilization of diglyceride species in biosynthesis of these glycerolipids, or modification of glycerolipids after their initial synthesis.", "contents": "Lipids of cultured hepatoma cells: VII. Structural analyses of glycerolipids in minimal deviation hepatoma 7288C. Phosphatidylcholine. phosphatidylethanolamine, and triglycerides were isolated from minimal deviation hepatoma 7288C cells cultured as monolayers to confluency in roller flasks containing Swim's 77 medium supplemented with 5% fetal calf serum, plus 20%, 10%, or 5% bovine serum. Fatty acid distribution at each position of glycerol was determined for the 3 glycerolipid classes, and carbon number distributions of triglycerides and diglycerides derived from phosphatidylcholine and phosphatidylethanolamine were quantitated by high temperature gas liquid chromatography. Fatty acid composition was only marginally affected by the level of bovine serum in the culture medium. Percentage composition of fatty acids esterified at each position of the 3 glycerolipids was different, indicating a nonrandom distribution of acyl groups in triglycerides and the 2 diacyl phosphatides. The carbon number distribution of diglycerides derived from phosphatidylcholine and phosphatidylethanolamine was different, and neither carbon number distribution agreed with the calculated 1-random, 2-random diacyl distribution, thus indicating pairing of certain acids in the diglycerides derived from these phospholipd classes. The determined triglyceride carbon number distributions did not show complete agreement with those calculated, assuming a 1-random, 2-random, 3-random type of fatty acyl distribution, suggesting preferential pairing of some acids in this lipid class. The 1-, 2-diglycerides derived from phosphatidylcholine, phosphatidylethanolamine, and triglycerides differed, indicating either selectivity in utilization of diglyceride species in biosynthesis of these glycerolipids, or modification of glycerolipids after their initial synthesis."} {"id": "PMID:170494", "title": "Effect of hypoglycemia on extracellular levels of cyclic AMP in man.", "content": "This study was designed to assess the response of cyclic AMP to \"endogenous\" hormonal stimulation resulting from insulin-induced hypoglycemia. Insulin was administered to four normal subjects and four adrenalectomized patients. Hypoglycemia resulted in four-fold increases in plasma cyclic AMP. This response is thought to be secondary to beta-adrenergic stimulation for the following reasons: (1) the response was absent in adrenalectomized, cortisol-treated subjects; (2) it was abolished by propranolol; and (3) urinary excretion of cyclic AMP did not reflect the rise in plasma cyclic AMP.", "contents": "Effect of hypoglycemia on extracellular levels of cyclic AMP in man. This study was designed to assess the response of cyclic AMP to \"endogenous\" hormonal stimulation resulting from insulin-induced hypoglycemia. Insulin was administered to four normal subjects and four adrenalectomized patients. Hypoglycemia resulted in four-fold increases in plasma cyclic AMP. This response is thought to be secondary to beta-adrenergic stimulation for the following reasons: (1) the response was absent in adrenalectomized, cortisol-treated subjects; (2) it was abolished by propranolol; and (3) urinary excretion of cyclic AMP did not reflect the rise in plasma cyclic AMP."} {"id": "PMID:170497", "title": "[Frequency and distribution of types of hyperlipoproteinemia with life-shortening risk factors among ambulant patients (author's transl)].", "content": "It is reported of 726 patients incidentally elected and mainly with life-shortening risk factors. 341 (47.1p.c.) showed an increased concentration of neutral fats and/or total cholesterol in the serum. Type IV (49.8 p.c.) according to Fredrickson was observed most frequently, followed by type IIb (31.1 p.c.) and by type IIa (19.1 p.c.). Most of the patients with hyperlipoproteinemia were overweight (53.1 p.c.), 33.6 p.c. suffered from arterial hypertension, 25.3 p.c. from diseases of the liver, 10.9 p.c. from coronary heart diseases, and 8.7 p.c. from manifest diabetes mellitus. The distribution of different types of hyperlipoproteinemia among the various diseases deviates from that of the total number of patients observed in this study. Cases of hyperlipoproteinemia were observed most frequently in diseases of the kidney with arterial hypertension (62.7 p.c.), coronary heart diseases (60.8 p.c.), manifest gout (60.0 p.c.), manifest diabetes mellitus (58.7 p.c.), and hyperuricemia without symptoms (55.8 p.c.). Type-IV-hyperlipoproteinemia was observed most frequently within the different groups of patients with life-shortening risk factors. An exception was the group of patients suffering from malignancies. Type IIb was found most frequently within the group of patients suffering from malignancies.", "contents": "[Frequency and distribution of types of hyperlipoproteinemia with life-shortening risk factors among ambulant patients (author's transl)]. It is reported of 726 patients incidentally elected and mainly with life-shortening risk factors. 341 (47.1p.c.) showed an increased concentration of neutral fats and/or total cholesterol in the serum. Type IV (49.8 p.c.) according to Fredrickson was observed most frequently, followed by type IIb (31.1 p.c.) and by type IIa (19.1 p.c.). Most of the patients with hyperlipoproteinemia were overweight (53.1 p.c.), 33.6 p.c. suffered from arterial hypertension, 25.3 p.c. from diseases of the liver, 10.9 p.c. from coronary heart diseases, and 8.7 p.c. from manifest diabetes mellitus. The distribution of different types of hyperlipoproteinemia among the various diseases deviates from that of the total number of patients observed in this study. Cases of hyperlipoproteinemia were observed most frequently in diseases of the kidney with arterial hypertension (62.7 p.c.), coronary heart diseases (60.8 p.c.), manifest gout (60.0 p.c.), manifest diabetes mellitus (58.7 p.c.), and hyperuricemia without symptoms (55.8 p.c.). Type-IV-hyperlipoproteinemia was observed most frequently within the different groups of patients with life-shortening risk factors. An exception was the group of patients suffering from malignancies. Type IIb was found most frequently within the group of patients suffering from malignancies."} {"id": "PMID:170498", "title": "Extracellular proteins in five clostridial species from human infections.", "content": "347 strains from human infections were identified by gas-liquid chromatography of metabolic products and by conventional tests. Simple agar-plate assays were used to analyze the ability to form extracellular proteins. More than 90% of all strains were hemolytic on agar containing rabbit erythrocytes and all were gelatinase producers. All strains of C. bifermantans, C. sordelli, and C. sporogenes were also caseinolytic on skimmed-milk agar, but strains of C. perfringens, C. novyi types A and B were not. Less than 10% of C. perfringens strains were producers of elastase and staphylolytic enzyme and all other species were non-producers. All C. perfringens, C. novyii, C. bifermentans, and C. sordelli were lecithinase producers, but C. sporogenes was not. All strains of C. sporogenes formed deoxyribonuclease, while a varying number of the other species showed a positive reaction.", "contents": "Extracellular proteins in five clostridial species from human infections. 347 strains from human infections were identified by gas-liquid chromatography of metabolic products and by conventional tests. Simple agar-plate assays were used to analyze the ability to form extracellular proteins. More than 90% of all strains were hemolytic on agar containing rabbit erythrocytes and all were gelatinase producers. All strains of C. bifermantans, C. sordelli, and C. sporogenes were also caseinolytic on skimmed-milk agar, but strains of C. perfringens, C. novyi types A and B were not. Less than 10% of C. perfringens strains were producers of elastase and staphylolytic enzyme and all other species were non-producers. All C. perfringens, C. novyii, C. bifermentans, and C. sordelli were lecithinase producers, but C. sporogenes was not. All strains of C. sporogenes formed deoxyribonuclease, while a varying number of the other species showed a positive reaction."} {"id": "PMID:170499", "title": "The effect of an immunosuppressive drug (azathioprine) on the latent infection of marmoset monkeys (Callithrix jacchus) with the oncogenic Herpesvirus saimiri.", "content": "Callithrix jacchus (CJ) marmoset monkeys can be latently infected with Herpesvirus saimiri (HVS). In order to determine whether this resistance to the oncogenic potential of HVS could be due to the immune surveillance, azathioprine, a known immunosuppressive drug, was given to 7 latently infected CJ marmosets. The animals died within 147 days probably from side effect caused by azathioprine, but no animal developed a tumor.", "contents": "The effect of an immunosuppressive drug (azathioprine) on the latent infection of marmoset monkeys (Callithrix jacchus) with the oncogenic Herpesvirus saimiri. Callithrix jacchus (CJ) marmoset monkeys can be latently infected with Herpesvirus saimiri (HVS). In order to determine whether this resistance to the oncogenic potential of HVS could be due to the immune surveillance, azathioprine, a known immunosuppressive drug, was given to 7 latently infected CJ marmosets. The animals died within 147 days probably from side effect caused by azathioprine, but no animal developed a tumor."} {"id": "PMID:170495", "title": "[Ultrastructure of Thiocapsa roseopersicina under various cultivation conditions].", "content": "The cells of the purple sulphur bacterium Thiocapsa roseopersicina, strain BBS, growing in the light and in the darkness, contain chromatophores of the normal vesicular type. The amount and dimensions of the vesicules in the cells depend on the composition of the medium and the conditions of cultivation. During anaerobic growth of the bacterium in the light in the medium with pyruvate, large cells appear with complicate invaginations of the cytoplasmic membrane. The cells may contain, besides drops of sulphur, polyphosphates, and poly-beta-hydroxybutyric acid, spherical inclusions of a fine-grain structure.", "contents": "[Ultrastructure of Thiocapsa roseopersicina under various cultivation conditions]. The cells of the purple sulphur bacterium Thiocapsa roseopersicina, strain BBS, growing in the light and in the darkness, contain chromatophores of the normal vesicular type. The amount and dimensions of the vesicules in the cells depend on the composition of the medium and the conditions of cultivation. During anaerobic growth of the bacterium in the light in the medium with pyruvate, large cells appear with complicate invaginations of the cytoplasmic membrane. The cells may contain, besides drops of sulphur, polyphosphates, and poly-beta-hydroxybutyric acid, spherical inclusions of a fine-grain structure."} {"id": "PMID:170505", "title": "The relation of polypeptide hormone structure and flexibility to receptor binding: the relevance of X-ray studies on insulins, glucagon and human placental lactogen.", "content": "Thr relevance of the crystal structure of the polypeptide hormones, insulin, glucagon and human placental lactogen to conformation and flexibility in solution and to receptor binding is considered. X-ray studies for crystal forms of glucagon, human placental lactogen and three insulin derivatives (A1 acetyl insulin, A1-t-butoxy carbonyl insulin and A1 2,2-dimethyl-3-formyl-L-thiazolidine-4-carbonyl insulin) are reported. Neither glucagon nor human placental lactogen are as ordered as insulin in the crystal form. Glucagon crystals undergo distinct transformations on changing the pH of the mother liquor from pH 9.5 to pH 6, indicating that the glucagon molecule is flexible in the crystal, as it is in solution. On the other hand all insulin analogues have a similar three dimensional structure to that of native insulin. Three dimensional difference Fourier studies of two insulin derivatives at 3 A resolution indicate the position of the modifying groups and define the small conformational changes which have occurred. The in vitro biological activity and receptor binding decrease with the increasing size of the group added to A1. The correlation of the structure analysis with the biological data strongly implicate a region close to A1 in receptor binding. Insulin appears to bind to the receptor in a specific conformation similar to that observed in the crystal structure and in solution; amino acid residues which are separated in the primary structure but brought into close juxtaposition in the tertiary structure are important for full potency.", "contents": "The relation of polypeptide hormone structure and flexibility to receptor binding: the relevance of X-ray studies on insulins, glucagon and human placental lactogen. Thr relevance of the crystal structure of the polypeptide hormones, insulin, glucagon and human placental lactogen to conformation and flexibility in solution and to receptor binding is considered. X-ray studies for crystal forms of glucagon, human placental lactogen and three insulin derivatives (A1 acetyl insulin, A1-t-butoxy carbonyl insulin and A1 2,2-dimethyl-3-formyl-L-thiazolidine-4-carbonyl insulin) are reported. Neither glucagon nor human placental lactogen are as ordered as insulin in the crystal form. Glucagon crystals undergo distinct transformations on changing the pH of the mother liquor from pH 9.5 to pH 6, indicating that the glucagon molecule is flexible in the crystal, as it is in solution. On the other hand all insulin analogues have a similar three dimensional structure to that of native insulin. Three dimensional difference Fourier studies of two insulin derivatives at 3 A resolution indicate the position of the modifying groups and define the small conformational changes which have occurred. The in vitro biological activity and receptor binding decrease with the increasing size of the group added to A1. The correlation of the structure analysis with the biological data strongly implicate a region close to A1 in receptor binding. Insulin appears to bind to the receptor in a specific conformation similar to that observed in the crystal structure and in solution; amino acid residues which are separated in the primary structure but brought into close juxtaposition in the tertiary structure are important for full potency."} {"id": "PMID:170506", "title": "Phosphatidic acid metabolism, calcium ions and transmitter release from electrically stimulated synaptosomes.", "content": "Synaptosomes isolated from guinea pig brain cortex were stimulated electrically in a medium containing [32P]-orthophosphate. The electrical stimulation caused increased labelling of phosphatidic acid in a synaptic vesicle fraction prepared by osmotic shock of the incubated synaptosomes. Electrical stimulation also provokes transmitter release from the synaptosomes. Both increased phosphatidate labelling and transmitter release required calcium ions in the medium. The effects are discussed in relation to earlier work with acetylcholine and the possible involvement of membrane phosphatidic acid in transmitter release by exocytosis.", "contents": "Phosphatidic acid metabolism, calcium ions and transmitter release from electrically stimulated synaptosomes. Synaptosomes isolated from guinea pig brain cortex were stimulated electrically in a medium containing [32P]-orthophosphate. The electrical stimulation caused increased labelling of phosphatidic acid in a synaptic vesicle fraction prepared by osmotic shock of the incubated synaptosomes. Electrical stimulation also provokes transmitter release from the synaptosomes. Both increased phosphatidate labelling and transmitter release required calcium ions in the medium. The effects are discussed in relation to earlier work with acetylcholine and the possible involvement of membrane phosphatidic acid in transmitter release by exocytosis."} {"id": "PMID:170507", "title": "Role of radiography in the diagnosis of mucoceles.", "content": "The role of radiography is of the utmost importance in the diagnosis of mucoceles. The use of plain films and tomograms enabled us to make the exact diagnosis of mucocele 19 out of 26 times. The patients had a mechanical proptosis, one sinus with a subnormal transparency was enlarged, and its walls were either thinned or broken at the place of a structural process of alteration. Orbital venography shows the venous shifting and ascertains the posterior extension and the extra-conal location of the tumour.", "contents": "Role of radiography in the diagnosis of mucoceles. The role of radiography is of the utmost importance in the diagnosis of mucoceles. The use of plain films and tomograms enabled us to make the exact diagnosis of mucocele 19 out of 26 times. The patients had a mechanical proptosis, one sinus with a subnormal transparency was enlarged, and its walls were either thinned or broken at the place of a structural process of alteration. Orbital venography shows the venous shifting and ascertains the posterior extension and the extra-conal location of the tumour."} {"id": "PMID:170512", "title": "Epithelial tumours of the lacrimal gland.", "content": "This paper reports a histopathological and follow-up study of 54 cases of epithelial tumours of the lacrimal gland. The findings confirm the view that accurate histological diagnosis is a reliable guide to the prognosis of these tumours and, therefore, to their clinical management. Since a thorough histological examination is of such clinical importance, treatment of these particular neoplasms should not be based upon evidence obtained from frozen sections of biopsies taken during operation. The histological criteria are described and illustrated and the follow-up analyzed in detail. Benign mixed tumours were the most common (55.5%) followed by adenoid cystic carcinoma (24.1%), other carcinomas, including two mucoepidermoid tumours (16.6%) and malignant mixed tumours (37.7%). In this series the prognosis for benign mixed tumours was excellent, despite occasional benigh recurrences, whereas the prognosis in the carcinoma group was correspondingly poor. Adenoid cystic carcinoma was the commonest form of carcinoma and commoner in the lacrimal gland than elsewhere. Although they run a highly malignant course, one case in this series is alive and well, without recurrence, after 17 years, indicating that the prognosis may well be favourable, providing the initial growth can be completely extirpated. The treatment of these tumours, already well described by SANDERS et al. [1962] is briefly summarized.", "contents": "Epithelial tumours of the lacrimal gland. This paper reports a histopathological and follow-up study of 54 cases of epithelial tumours of the lacrimal gland. The findings confirm the view that accurate histological diagnosis is a reliable guide to the prognosis of these tumours and, therefore, to their clinical management. Since a thorough histological examination is of such clinical importance, treatment of these particular neoplasms should not be based upon evidence obtained from frozen sections of biopsies taken during operation. The histological criteria are described and illustrated and the follow-up analyzed in detail. Benign mixed tumours were the most common (55.5%) followed by adenoid cystic carcinoma (24.1%), other carcinomas, including two mucoepidermoid tumours (16.6%) and malignant mixed tumours (37.7%). In this series the prognosis for benign mixed tumours was excellent, despite occasional benigh recurrences, whereas the prognosis in the carcinoma group was correspondingly poor. Adenoid cystic carcinoma was the commonest form of carcinoma and commoner in the lacrimal gland than elsewhere. Although they run a highly malignant course, one case in this series is alive and well, without recurrence, after 17 years, indicating that the prognosis may well be favourable, providing the initial growth can be completely extirpated. The treatment of these tumours, already well described by SANDERS et al. [1962] is briefly summarized."} {"id": "PMID:170514", "title": "[Diet in hyperuricemia (author's transl)].", "content": "The idea that, in view of potent drugs, the dietary treatment of a metabolic disease must be reserved for a small group of particularly susceptible patients or even for a minority of neurotically structured patients who would alone be capable of bearing the hardship of a consequent change of accustomed feeding habits needs correction. Considerably greater importance must be attached to dietetics in disorders of uric acid metabolism than formerly, particularly with a view to the status already gained by the dietary treatment of diabetes mellitus a long time ago. Dietetic therapy of familial hyperuricemia and its later clinical manifestation, gout, is a basic therapy of a preventive character. Because today, superiority is increasingly conceded to prophylaxis rather than to the treatment of late sequelae.", "contents": "[Diet in hyperuricemia (author's transl)]. The idea that, in view of potent drugs, the dietary treatment of a metabolic disease must be reserved for a small group of particularly susceptible patients or even for a minority of neurotically structured patients who would alone be capable of bearing the hardship of a consequent change of accustomed feeding habits needs correction. Considerably greater importance must be attached to dietetics in disorders of uric acid metabolism than formerly, particularly with a view to the status already gained by the dietary treatment of diabetes mellitus a long time ago. Dietetic therapy of familial hyperuricemia and its later clinical manifestation, gout, is a basic therapy of a preventive character. Because today, superiority is increasingly conceded to prophylaxis rather than to the treatment of late sequelae."} {"id": "PMID:170515", "title": "Chromosome damage in the bone marrow of mice treated with the methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea in the presence or absence of caffeine, and its relationship with thymoma induction.", "content": "A single dose (0.8 mmole/kg) of N-methyl-N-nitrosourea (MNUA) causes significantly more chromosome damage in the bone marrow of mice than a dose of equal toxicity to the animals, (1.1 mmole/kg) of methyl methanesulphonate (MMS) 6, 24 and 48 h after treatment. At these doses both agents alkylate bone-marrow DNA to similar extents, but only MNUA induces thymic lymphomata. The greater chromosome-damaging effects of MNUA are ascribed to the known differences in the pattern of DNA alkylation by each agent, in particular the much higher levels of O-6 methylguanine and phosphotriesters produced by MNUA. The greater chromosome-damaging effect of MNUA may account for its higher toxicity to the bone marrow which in turn may be a significant factor in the induction of thymomata. The enhancement by caffeine of chromosome damage seen particularly 48 h after MMS-treatment suggests that post-replication repair protects cells from the effects of DNA-methylation in vivo.", "contents": "Chromosome damage in the bone marrow of mice treated with the methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea in the presence or absence of caffeine, and its relationship with thymoma induction. A single dose (0.8 mmole/kg) of N-methyl-N-nitrosourea (MNUA) causes significantly more chromosome damage in the bone marrow of mice than a dose of equal toxicity to the animals, (1.1 mmole/kg) of methyl methanesulphonate (MMS) 6, 24 and 48 h after treatment. At these doses both agents alkylate bone-marrow DNA to similar extents, but only MNUA induces thymic lymphomata. The greater chromosome-damaging effects of MNUA are ascribed to the known differences in the pattern of DNA alkylation by each agent, in particular the much higher levels of O-6 methylguanine and phosphotriesters produced by MNUA. The greater chromosome-damaging effect of MNUA may account for its higher toxicity to the bone marrow which in turn may be a significant factor in the induction of thymomata. The enhancement by caffeine of chromosome damage seen particularly 48 h after MMS-treatment suggests that post-replication repair protects cells from the effects of DNA-methylation in vivo."} {"id": "PMID:170516", "title": "Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D.", "content": "In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown. In two children with hypoparathyroidism and one with pseudohypoparathyroidism we tested the hypothesis that in these conditions there is a defect in synthesis of 1 alpha,25-dihydroxyvitamin D3, the principal active metabolite of vitamin D. In both conditions, minute doses of the metabolite (0.04 to 0.08 mug per kilogram of body weight per day) quickly corrected hypocalcemia and increased intestinal calcium absorption. On the other hand, the effective dose of 25-hydroxyvitamin D3 to maintain normocalcemia was 3 to 4 mug per kilogram per day in the two conditions. Thus, the dosage ratio of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3 approximated 100:1. By contrast this ratio was approximately 3:1 in two infants with vitamin D deficiency, a condition in which optimal metabolism of vitamin D would be expected. These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism.", "contents": "Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown. In two children with hypoparathyroidism and one with pseudohypoparathyroidism we tested the hypothesis that in these conditions there is a defect in synthesis of 1 alpha,25-dihydroxyvitamin D3, the principal active metabolite of vitamin D. In both conditions, minute doses of the metabolite (0.04 to 0.08 mug per kilogram of body weight per day) quickly corrected hypocalcemia and increased intestinal calcium absorption. On the other hand, the effective dose of 25-hydroxyvitamin D3 to maintain normocalcemia was 3 to 4 mug per kilogram per day in the two conditions. Thus, the dosage ratio of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3 approximated 100:1. By contrast this ratio was approximately 3:1 in two infants with vitamin D deficiency, a condition in which optimal metabolism of vitamin D would be expected. These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism."} {"id": "PMID:170518", "title": "Homozygous familial hypercholesterolemia. A possible biochemical explanation of clinical heterogeneity.", "content": "Patients with homozygous familial hypercholesterolemia fall into two groups: one responds to diet and drug therapy; the other does not. Fibroblasts from patients in each group were compared for low-density lipoprotein suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein binding. In fibroblasts from four therapy-responsive patients, low-density lipoprotein (100 mug per milliliter) suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity to 41 +/- 12 per cent of control (without low-density lipoprotein) whereas fibroblast enzyme activity from two therapy-unresponsive patients was not suppressed (P less than 0.001). Low-density lipoprotein binding to fibroblasts from both groups was defective as compared to normal controls. Fibroblasts from two therapy-responsive patients had specific binding of low-density lipoprotein of 27 +/- 4 per cent of normal -- greater than the 12 +/- 2 per cent (P less than 0.005) binding to fibroblasts from one therapy-unresponsive patient. These biochemical differences may help explain the variable response to therapy in homozygous familial hypercholesterolemia.", "contents": "Homozygous familial hypercholesterolemia. A possible biochemical explanation of clinical heterogeneity. Patients with homozygous familial hypercholesterolemia fall into two groups: one responds to diet and drug therapy; the other does not. Fibroblasts from patients in each group were compared for low-density lipoprotein suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein binding. In fibroblasts from four therapy-responsive patients, low-density lipoprotein (100 mug per milliliter) suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity to 41 +/- 12 per cent of control (without low-density lipoprotein) whereas fibroblast enzyme activity from two therapy-unresponsive patients was not suppressed (P less than 0.001). Low-density lipoprotein binding to fibroblasts from both groups was defective as compared to normal controls. Fibroblasts from two therapy-responsive patients had specific binding of low-density lipoprotein of 27 +/- 4 per cent of normal -- greater than the 12 +/- 2 per cent (P less than 0.005) binding to fibroblasts from one therapy-unresponsive patient. These biochemical differences may help explain the variable response to therapy in homozygous familial hypercholesterolemia."} {"id": "PMID:170521", "title": "Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections.", "content": "Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials.", "contents": "Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections. Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials."} {"id": "PMID:170542", "title": "Immunization of pigs with the attenuated S- strain of Japanese encephalitis virus.", "content": "The attenuated S- strain of Japanese encephalitis virus was produced from a wild strain of this virus by serial cultivation in primary bovine kidney cell cultures at 30 degrees C. Pigs were inoculated with it and examined for ability to produce antibody and protect themselves from infection with a wild strain used for challenge. In pigs inoculated with a single dose of 10(6.5) approximately 10(7.5) TCID50 of the S- strain, the neutralizing antibody titer or hemagglutination-inhibiting antibody (HI) titer increased to 10 approximately 320. An antibody titer exceeding 10 was maintained for 2 approximately 9 weeks. In pigs inoculated twice with 10(6.5) approximately 10(7.0) TCID50 of the S- strain, HI titer increased to 80 approximately 640. In many of these pigs, HI titers of 80 approximately 160 persisted for more than 6 weeks. Pigs inoculated once or twice with 10(7.0) approximately 10(7.5) TCID50 of the S- strain were challenged by inoculation with 10(4.5) approximately 10(5.5) TCID50 of a wild strain and examined for the occurrence of viremia. As a result, an ability to protect from infection was demonstrated in pigs which showed an antibody titer surpassing 10 at the time of challenge. Pregnant sows inoculated with 10(7.0) TCID50 of the S- strain were challenged by inoculation with 10(7.0) TCID50 of a wild strain. Neither death nor infection occurred to any fetus harbored by them. From these results, it is concluded that the S- strain can be used as live virus vaccine for porcine practice.", "contents": "Immunization of pigs with the attenuated S- strain of Japanese encephalitis virus. The attenuated S- strain of Japanese encephalitis virus was produced from a wild strain of this virus by serial cultivation in primary bovine kidney cell cultures at 30 degrees C. Pigs were inoculated with it and examined for ability to produce antibody and protect themselves from infection with a wild strain used for challenge. In pigs inoculated with a single dose of 10(6.5) approximately 10(7.5) TCID50 of the S- strain, the neutralizing antibody titer or hemagglutination-inhibiting antibody (HI) titer increased to 10 approximately 320. An antibody titer exceeding 10 was maintained for 2 approximately 9 weeks. In pigs inoculated twice with 10(6.5) approximately 10(7.0) TCID50 of the S- strain, HI titer increased to 80 approximately 640. In many of these pigs, HI titers of 80 approximately 160 persisted for more than 6 weeks. Pigs inoculated once or twice with 10(7.0) approximately 10(7.5) TCID50 of the S- strain were challenged by inoculation with 10(4.5) approximately 10(5.5) TCID50 of a wild strain and examined for the occurrence of viremia. As a result, an ability to protect from infection was demonstrated in pigs which showed an antibody titer surpassing 10 at the time of challenge. Pregnant sows inoculated with 10(7.0) TCID50 of the S- strain were challenged by inoculation with 10(7.0) TCID50 of a wild strain. Neither death nor infection occurred to any fetus harbored by them. From these results, it is concluded that the S- strain can be used as live virus vaccine for porcine practice."} {"id": "PMID:170543", "title": "Histopathology of hemorrhagic enteritis in turkeys.", "content": "In the summer of 1972, a disease of turkeys manifesting hemorrhagic diarrhea as a main clinical symptom and hemorrhagic enteritis as a necropsy finding broke out on a turkey farm in Japan. Seven-week-old Large White turkeys suffering from this disease were studied histopathologically and electron microscopically. Clinically, affected birds showed bloody diarrhea. Death occurred to them after an acute course. In the blood film, immature monocytes were higher in count in them than in healthy birds. Necropsy revealed a number of dark red bloody clots in the intestinal tract, many petechiae in the mucous membrane of small intestine and ceca, and atrophy of the spleen. The histopathological changes characteristic of this disease were acute hemorrhagic enteritis, degenerative changes of lymphatic tissue, proliferation of reticuloendothelial cells all over the body, and formation of intranuclear inclusion bodies in these cells. By electron microscopy, viral particles showing a crystalline array were found in the nuclei of reticuloendothelial cells. Viral particles which had electron-dense nucleoids and a naked hexagonal shape were about 80 nm in average diameter. The ultrastructural features of those inclusion bodies were identical with those of avian adenovirus.", "contents": "Histopathology of hemorrhagic enteritis in turkeys. In the summer of 1972, a disease of turkeys manifesting hemorrhagic diarrhea as a main clinical symptom and hemorrhagic enteritis as a necropsy finding broke out on a turkey farm in Japan. Seven-week-old Large White turkeys suffering from this disease were studied histopathologically and electron microscopically. Clinically, affected birds showed bloody diarrhea. Death occurred to them after an acute course. In the blood film, immature monocytes were higher in count in them than in healthy birds. Necropsy revealed a number of dark red bloody clots in the intestinal tract, many petechiae in the mucous membrane of small intestine and ceca, and atrophy of the spleen. The histopathological changes characteristic of this disease were acute hemorrhagic enteritis, degenerative changes of lymphatic tissue, proliferation of reticuloendothelial cells all over the body, and formation of intranuclear inclusion bodies in these cells. By electron microscopy, viral particles showing a crystalline array were found in the nuclei of reticuloendothelial cells. Viral particles which had electron-dense nucleoids and a naked hexagonal shape were about 80 nm in average diameter. The ultrastructural features of those inclusion bodies were identical with those of avian adenovirus."} {"id": "PMID:170544", "title": "Histopathology of feline panleukopenia in domestic cats.", "content": "Histopathological observations were carried out on 17 domestic cats naturally affected with feline panleukopenia. Principal lesions were found in the intestine, bone marrow, and lymphoid organs. Intestinal lesions were characterized by degenerative changes accompanied by the appearance of intranuclear inclusion bodies in the epithelial cells of the crypts. In contrast to the crypts, the villi were seldom involved. Hypoplasia, parenchymal degeneration, and activation of the reticuloendothelial system were observed in the bone marrow and lymphoid organs. Intranuclear inclusion bodies were found occasionally also in the reticular and parenchymal cells of the bone marrow, lymphoid organs, liver, adrenals, and pancreas. Most of the inclusion bodies were amphophilic when stained with hematoxylin and eosin and occupied the whole area of the nucleus without producing any zone of clear halo. While cells bearing inclusion bodies underwent degenerative changes constantly in the intestinal crypts, the formation of inclusion body was not accompanied by the degeneration of corresponding cells in any other organ. Pathological changes as mentioned above were considered to be closely related to the systemic infection of feline panleukopenia virus.", "contents": "Histopathology of feline panleukopenia in domestic cats. Histopathological observations were carried out on 17 domestic cats naturally affected with feline panleukopenia. Principal lesions were found in the intestine, bone marrow, and lymphoid organs. Intestinal lesions were characterized by degenerative changes accompanied by the appearance of intranuclear inclusion bodies in the epithelial cells of the crypts. In contrast to the crypts, the villi were seldom involved. Hypoplasia, parenchymal degeneration, and activation of the reticuloendothelial system were observed in the bone marrow and lymphoid organs. Intranuclear inclusion bodies were found occasionally also in the reticular and parenchymal cells of the bone marrow, lymphoid organs, liver, adrenals, and pancreas. Most of the inclusion bodies were amphophilic when stained with hematoxylin and eosin and occupied the whole area of the nucleus without producing any zone of clear halo. While cells bearing inclusion bodies underwent degenerative changes constantly in the intestinal crypts, the formation of inclusion body was not accompanied by the degeneration of corresponding cells in any other organ. Pathological changes as mentioned above were considered to be closely related to the systemic infection of feline panleukopenia virus."} {"id": "PMID:170545", "title": "Mode of action of sodium nitroprusside on vascular smooth muscle.", "content": "1. Sodium nitroprusside is a potent relaxant of smooth muscles with a predominantly tonic response, e.g. rat aorta contracted by noradrenaline, angiotensin II, Phe2-Lys8-vasopressin, BaC1(2), or KC1, and guinea-pig tracheal smooth muscle contracted by carbachol. 2. Smooth muscle preparations from the splanchnic region and with varying degrees of phasic contractility are less sensitive and develop tachyphylaxis (portal vein, duodenum of the rat) or are unresponsive to sodium nitroprusside (vas deferens, uterus of the rat). 3. Cardiac auricles of the guinea pig are not affected by sodium nitroprusside in either frequency or amplitude or spontaneous contractions. 4. Sdium nitroprusside causes a parallel shift of the dose-response curve of rat aorta to noradrenaline to the right and reduces the maximum response. 5. The drug has no blocking or stimulant effect on alpha- or beta-adrenoceptors, respectively. 6. Sodium nitroprusside inhibits the contractile response of calcium-depleted depolarized rat aorta to extra-cellular calcium. Like verapamil, it inhibits the increment in 45calcium uptake of rabbit aorta elicited by K+. Sodium nitroprusside significantly reduced 45calcium binding by microsomes prepared from rabbit aorta. 7. Rabbit aorta was incubated with lanthanum chloride to prevent calcium influx; sodium nitroprusside reduced the maintained rapid contraction phase in response to noradrenaline which is believed to be based on the intracellular activation of calcium. 8. In rat aorta, cellular cAMP and ATP levels were not found to be affected by the drug. 9. Rabbit aorta, \"skinned\" by glycerination is unresponsive to sdoium nitroprusside. 10. It is concluded that sodium nitropruside acts on exictation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium.", "contents": "Mode of action of sodium nitroprusside on vascular smooth muscle. 1. Sodium nitroprusside is a potent relaxant of smooth muscles with a predominantly tonic response, e.g. rat aorta contracted by noradrenaline, angiotensin II, Phe2-Lys8-vasopressin, BaC1(2), or KC1, and guinea-pig tracheal smooth muscle contracted by carbachol. 2. Smooth muscle preparations from the splanchnic region and with varying degrees of phasic contractility are less sensitive and develop tachyphylaxis (portal vein, duodenum of the rat) or are unresponsive to sodium nitroprusside (vas deferens, uterus of the rat). 3. Cardiac auricles of the guinea pig are not affected by sodium nitroprusside in either frequency or amplitude or spontaneous contractions. 4. Sdium nitroprusside causes a parallel shift of the dose-response curve of rat aorta to noradrenaline to the right and reduces the maximum response. 5. The drug has no blocking or stimulant effect on alpha- or beta-adrenoceptors, respectively. 6. Sodium nitroprusside inhibits the contractile response of calcium-depleted depolarized rat aorta to extra-cellular calcium. Like verapamil, it inhibits the increment in 45calcium uptake of rabbit aorta elicited by K+. Sodium nitroprusside significantly reduced 45calcium binding by microsomes prepared from rabbit aorta. 7. Rabbit aorta was incubated with lanthanum chloride to prevent calcium influx; sodium nitroprusside reduced the maintained rapid contraction phase in response to noradrenaline which is believed to be based on the intracellular activation of calcium. 8. In rat aorta, cellular cAMP and ATP levels were not found to be affected by the drug. 9. Rabbit aorta, \"skinned\" by glycerination is unresponsive to sdoium nitroprusside. 10. It is concluded that sodium nitropruside acts on exictation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium."} {"id": "PMID:170546", "title": "The effect of Solanum malacoxylon on rachitic bone lesions in the rat.", "content": "The plant Solanum malacoxylon (S.M.) is known to cause severe soft tissue calcifications in cattle and sheep and has recently become of special interest since it exerts biological actions which resemble those of vitamin D. In order to investigate whether S.M. is capable to improve the rachitic bone changes in vitamin D and phosphate deficient rats, a watery extract of 50, 100 and 200 mg S.M. was fed daily to these animals over a period of 10 days. The width of epiphyseal plates was compared after the time with those of rats treates with 0, 0.225, 0.45, and 0.9 IU of vitamin D3 daily. There was a dose related curative effect of S.M. on the epiphyseal lesions very similar to that of vitamin D3. The hypercalcemic and hyperphosphatemic effect of S.M. was identical to that of vitamin D3. The 25-hydroxy-vitamin D serum levels remained almost undetectable in the S.M. treated rats as well as in the vitamin D3 treated animals.", "contents": "The effect of Solanum malacoxylon on rachitic bone lesions in the rat. The plant Solanum malacoxylon (S.M.) is known to cause severe soft tissue calcifications in cattle and sheep and has recently become of special interest since it exerts biological actions which resemble those of vitamin D. In order to investigate whether S.M. is capable to improve the rachitic bone changes in vitamin D and phosphate deficient rats, a watery extract of 50, 100 and 200 mg S.M. was fed daily to these animals over a period of 10 days. The width of epiphyseal plates was compared after the time with those of rats treates with 0, 0.225, 0.45, and 0.9 IU of vitamin D3 daily. There was a dose related curative effect of S.M. on the epiphyseal lesions very similar to that of vitamin D3. The hypercalcemic and hyperphosphatemic effect of S.M. was identical to that of vitamin D3. The 25-hydroxy-vitamin D serum levels remained almost undetectable in the S.M. treated rats as well as in the vitamin D3 treated animals."} {"id": "PMID:170548", "title": "Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney.", "content": "This paper reviews the physiology of antidiuretic hormone, including the factors involving the formation, storage and release of the hormone, the metabolism of vasopressin and its physiologic and pharmacologic effects on water and electrolyte transport. The consequences of both deficiency and excess of the hormone are also discussed.", "contents": "Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney. This paper reviews the physiology of antidiuretic hormone, including the factors involving the formation, storage and release of the hormone, the metabolism of vasopressin and its physiologic and pharmacologic effects on water and electrolyte transport. The consequences of both deficiency and excess of the hormone are also discussed."} {"id": "PMID:170549", "title": "Catecholamines and renal water excretion.", "content": "The in vivo mechanisms whereby systemic alpha- and beta-adrenergic stimulation exert opposing effects on renal water excretion are reviewed. An extrarenal mechanism is suggested since the effect of intravenous infusion of norepinephrine or isoproterenol on water excretion cannot be mimicked by the intrarenal administration of these agents. A ROLE OF VASOPRESSIN IS IMPLICATED SINCE NEITHER MAN NOR DOG WITHOUT A PITUITARY SOURCE OF VASOPRESSIN DEMONSTRATE THE SAME EFFECT OF CATECHOLAMINES ON WATER EXCRETION AS OBSERVED IN INTACT MAN AND DOG. Evidence also is presented that systemic alpha- and beta-adrenergic stimulation affect vasopressin release primarily by altering baroreceptor tone. The potential role of the autonomic nervous system in mediating other nonosmotic stimuli for vasopressin is discussed.", "contents": "Catecholamines and renal water excretion. The in vivo mechanisms whereby systemic alpha- and beta-adrenergic stimulation exert opposing effects on renal water excretion are reviewed. An extrarenal mechanism is suggested since the effect of intravenous infusion of norepinephrine or isoproterenol on water excretion cannot be mimicked by the intrarenal administration of these agents. A ROLE OF VASOPRESSIN IS IMPLICATED SINCE NEITHER MAN NOR DOG WITHOUT A PITUITARY SOURCE OF VASOPRESSIN DEMONSTRATE THE SAME EFFECT OF CATECHOLAMINES ON WATER EXCRETION AS OBSERVED IN INTACT MAN AND DOG. Evidence also is presented that systemic alpha- and beta-adrenergic stimulation affect vasopressin release primarily by altering baroreceptor tone. The potential role of the autonomic nervous system in mediating other nonosmotic stimuli for vasopressin is discussed."} {"id": "PMID:170550", "title": "Kidney and calcitonin.", "content": "Calcitonin, whatever its origin, produces a decrease in the renal tubular reabsorption of sodium, phosphate and calcium in man and in the rat. Renal receptors for calcitonin have been demonstrated in the membranes of rat tubular cells using 125I salmon calcitonin as a tracer. Hormone-receptor interaction initiates the activation of membrane adenyl cyclase. In the rat and in man, the kidney plays a major role in degradation of both human and salmon calcitonin. Plasma levels of immunoreactive calcitonin are high in chronic renal failure. The question of the physiological role of calcitonin on kidney function is still unsettled.", "contents": "Kidney and calcitonin. Calcitonin, whatever its origin, produces a decrease in the renal tubular reabsorption of sodium, phosphate and calcium in man and in the rat. Renal receptors for calcitonin have been demonstrated in the membranes of rat tubular cells using 125I salmon calcitonin as a tracer. Hormone-receptor interaction initiates the activation of membrane adenyl cyclase. In the rat and in man, the kidney plays a major role in degradation of both human and salmon calcitonin. Plasma levels of immunoreactive calcitonin are high in chronic renal failure. The question of the physiological role of calcitonin on kidney function is still unsettled."} {"id": "PMID:170551", "title": "Vitamin d and the kidney.", "content": "The biologically active form of vitamin D3, 1,25-dihydroxycholecalciferol is produced by the kidney. The biosynthesis of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol is apparently controlled and important factors in this control are dietary calcium and phosphorus, and parathyroid hormone secretion. The direct effects of vitamin D and its metabolites on renal function are uncertain. Patients with chronic renal failure have defective synthesis of 1,25-dihydroxycholecalciferol. Uremic patients treated with small doses of 1,25-dihydroxycholecalciferol or 1 alpha-hydroxycholecalciferol show increased intestinal calcium absorption and bone healing.", "contents": "Vitamin d and the kidney. The biologically active form of vitamin D3, 1,25-dihydroxycholecalciferol is produced by the kidney. The biosynthesis of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol is apparently controlled and important factors in this control are dietary calcium and phosphorus, and parathyroid hormone secretion. The direct effects of vitamin D and its metabolites on renal function are uncertain. Patients with chronic renal failure have defective synthesis of 1,25-dihydroxycholecalciferol. Uremic patients treated with small doses of 1,25-dihydroxycholecalciferol or 1 alpha-hydroxycholecalciferol show increased intestinal calcium absorption and bone healing."} {"id": "PMID:170552", "title": "Morphological changes of astrocyte-like cells induced by serum beta-lipoprotein in brain cell culture.", "content": "When added to brain cell cultures of newborn rats, serum and, in particular, its beta-lipoprotein fraction caused significant morphological transformations of astrocyte-like cells present in the culture. The changes were instantaneous as they appeared within 1 min after addition of beta-lipoprotein and they were characterized by swelling and loss of cellular processes of all astrocyte-like cells present. The lipoprotein effect was reversed after a period of about 7 h. Since the blood-brain and blood-spinal fluid barrier in multiple sclerosis is decreased towards serum macromolecules, i.e. the serum beta-lipoprotein, this protein may enter the central nervous system and thereby initiate a demyelinating process.", "contents": "Morphological changes of astrocyte-like cells induced by serum beta-lipoprotein in brain cell culture. When added to brain cell cultures of newborn rats, serum and, in particular, its beta-lipoprotein fraction caused significant morphological transformations of astrocyte-like cells present in the culture. The changes were instantaneous as they appeared within 1 min after addition of beta-lipoprotein and they were characterized by swelling and loss of cellular processes of all astrocyte-like cells present. The lipoprotein effect was reversed after a period of about 7 h. Since the blood-brain and blood-spinal fluid barrier in multiple sclerosis is decreased towards serum macromolecules, i.e. the serum beta-lipoprotein, this protein may enter the central nervous system and thereby initiate a demyelinating process."} {"id": "PMID:170555", "title": "Effect of intraventricular glutamate on ACTH release.", "content": "Sodium glutamate infused into the 3rd ventricle is a potent stimulus of ACTH release, as shown by the rise in plasma corticosterone levels. Glutamate failed to consistently increase the plasma corticosterone level in rats with deafferentation of the medial basal hypothalamus (MBH). We suggest that intraventricular glutamate interferes with central nervous function outside the MBH and stimulates ACTH release via afferent neural pathways.", "contents": "Effect of intraventricular glutamate on ACTH release. Sodium glutamate infused into the 3rd ventricle is a potent stimulus of ACTH release, as shown by the rise in plasma corticosterone levels. Glutamate failed to consistently increase the plasma corticosterone level in rats with deafferentation of the medial basal hypothalamus (MBH). We suggest that intraventricular glutamate interferes with central nervous function outside the MBH and stimulates ACTH release via afferent neural pathways."} {"id": "PMID:170553", "title": "[Immunoglobulin G level in the serum of patients with polyneuropathies].", "content": "In the serum of patients with polyneuropathies of various aetiology the immunoglobulin G level was determined quantitatively using the so-called disc precipitation test. Fifty serum samples were investigated. The IgG level was higher (p less than 0.05) in the group of patients with polyneuropathy as compared with the control group. No differences were observed in the IgG level between different types of polyneuropathy which may be due to small number of cases in various groups.", "contents": "[Immunoglobulin G level in the serum of patients with polyneuropathies]. In the serum of patients with polyneuropathies of various aetiology the immunoglobulin G level was determined quantitatively using the so-called disc precipitation test. Fifty serum samples were investigated. The IgG level was higher (p less than 0.05) in the group of patients with polyneuropathy as compared with the control group. No differences were observed in the IgG level between different types of polyneuropathy which may be due to small number of cases in various groups."} {"id": "PMID:170554", "title": "[Surgical management and therapeutic results in 114 cases of pituitary adenoma].", "content": "In the reported group of 114 cases the overall operative mortality was 3,5% and when two incurable cases are escluded this mortality falls to 1,7%. An essential change in the management of this disease was abandoning of postoperative radiotherapy and increasing of the extent of tumour removal. This decision was based on the view that despite weak antigenicity of the neoplasm immune mechanisms mobilized after radical operation are sufficient to inhibit or even destroy the remaining tumour tissue. In the light of eight years of experience with this method it seems that it will pass the test of time.", "contents": "[Surgical management and therapeutic results in 114 cases of pituitary adenoma]. In the reported group of 114 cases the overall operative mortality was 3,5% and when two incurable cases are escluded this mortality falls to 1,7%. An essential change in the management of this disease was abandoning of postoperative radiotherapy and increasing of the extent of tumour removal. This decision was based on the view that despite weak antigenicity of the neoplasm immune mechanisms mobilized after radical operation are sufficient to inhibit or even destroy the remaining tumour tissue. In the light of eight years of experience with this method it seems that it will pass the test of time."} {"id": "PMID:170559", "title": "Cytosome morphology and distribution of generalized ceroidlipofuscinosis in a twenty-eight month old boy with normal myeloperoxidase activity.", "content": "A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease.", "contents": "Cytosome morphology and distribution of generalized ceroidlipofuscinosis in a twenty-eight month old boy with normal myeloperoxidase activity. A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease."} {"id": "PMID:170562", "title": "Adipose tissue metabolism in essential fatty acid deficienty. Effects of prostaglandin e1, epinephrine, and ACTH.", "content": "In an effort to better define some of the metabolic changes that accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or 6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and glyceride-glycerol was determined. It was found that EFAD increased glucose uptake over controls which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls. ACTH1-18 (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups, respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups, respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the inhibitory action of the catecholamine in both groups. It is suggested that, although EFA serve as prostaglandin precursors, the effects of EFAD on the metabolism of fat cells cannot be reversed by PGE1, in vitro. However, these fat cells retain their responsiveness to the action of both lipolytic (ACTH and epinephrine) and antilipolytic (PGE1) agents.", "contents": "Adipose tissue metabolism in essential fatty acid deficienty. Effects of prostaglandin e1, epinephrine, and ACTH. In an effort to better define some of the metabolic changes that accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or 6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and glyceride-glycerol was determined. It was found that EFAD increased glucose uptake over controls which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls. ACTH1-18 (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups, respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups, respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the inhibitory action of the catecholamine in both groups. It is suggested that, although EFA serve as prostaglandin precursors, the effects of EFAD on the metabolism of fat cells cannot be reversed by PGE1, in vitro. However, these fat cells retain their responsiveness to the action of both lipolytic (ACTH and epinephrine) and antilipolytic (PGE1) agents."} {"id": "PMID:170567", "title": "Food poisoning--four unusual episodes.", "content": "Four unusual outbreaks of food poisoning occurring in the Dunedin Health District during the period 1971-1973 are described. These involved a contaminated cordial, a death associated with a Clostridium perfringens outbreak, salmonellosis and infectious hepatitis in persons eating uncooked shellfish and symptoms associated with the ingestion of a normally edible fish--the trumpeter.", "contents": "Food poisoning--four unusual episodes. Four unusual outbreaks of food poisoning occurring in the Dunedin Health District during the period 1971-1973 are described. These involved a contaminated cordial, a death associated with a Clostridium perfringens outbreak, salmonellosis and infectious hepatitis in persons eating uncooked shellfish and symptoms associated with the ingestion of a normally edible fish--the trumpeter."} {"id": "PMID:170572", "title": "Electron microscopic demonstration of hormone-producing metastatic carcinoma of the choroid from the bronchus.", "content": "Clinical, laboratory and pathological findings of a patient in bronchial carcinoma with choroidal metastasis were presented. X-ray examination of the chest suggested the tumor shadow in the posterior segmental bronchus of the right upper lobe of the lung (r-B2b), while funduscopy and fluorescein angiography revealed the presence of choroidal tumor. ACTH levels in tumor tissues at autopsy and in serum were measured and definitely demonstrated and elevated. Histopathologically, the primary lesion was r-B2b and diagnosed as a mucocellular type of adenocarcinoma. The choroidal lesion was metastatic carcinoma. Electron microscopic examination of the choroidal lesion reembedded for electron microscopy from celloidin-embedded materials for light microscopy could reveal the presence of characteristic cytoplasmic granules referred to as neurosecretory-type granules. It is extremely rare that a hormone-producing metastatic carcinoma of the choroid from the bronchus has been proved.", "contents": "Electron microscopic demonstration of hormone-producing metastatic carcinoma of the choroid from the bronchus. Clinical, laboratory and pathological findings of a patient in bronchial carcinoma with choroidal metastasis were presented. X-ray examination of the chest suggested the tumor shadow in the posterior segmental bronchus of the right upper lobe of the lung (r-B2b), while funduscopy and fluorescein angiography revealed the presence of choroidal tumor. ACTH levels in tumor tissues at autopsy and in serum were measured and definitely demonstrated and elevated. Histopathologically, the primary lesion was r-B2b and diagnosed as a mucocellular type of adenocarcinoma. The choroidal lesion was metastatic carcinoma. Electron microscopic examination of the choroidal lesion reembedded for electron microscopy from celloidin-embedded materials for light microscopy could reveal the presence of characteristic cytoplasmic granules referred to as neurosecretory-type granules. It is extremely rare that a hormone-producing metastatic carcinoma of the choroid from the bronchus has been proved."} {"id": "PMID:170573", "title": "[Serological screening of streptococci. Comparison of 2 methods of slide agglutination, one with streptolysin alone, the other with several enzymes (Streptozymes)].", "content": "Using 100 sera randomly selected, the clinical characteristis of which were known, we compared two methods of rapid detection of streptococcal infections by slide agglutination. One was the classical latex test for detection of anti-streptolysin O, the other was the streptozyme test. The latter reagent detects the presence of 5 streptococcal antibodies, anti-streptolysin O, anti-streptokinase, anti-streptohyaluronidase, anti-desoxyribonuclease and anti-nicotinamide-adenine-dinucleotidase. It was found to be more sensitive than the latex test, for antistreptolysin O. Estimations of A.S.K. and A.S.H. confirmed also the greater specificity of the streptozyme test and showed that, thanks to the presence of supplementary enzymes, it may be positive earlier than the A.S.O. latex test. Finally, used as a semi-quantitative method, streptozyme is useful to follow up approximately in the laboratory, the course of streptococcal infections.", "contents": "[Serological screening of streptococci. Comparison of 2 methods of slide agglutination, one with streptolysin alone, the other with several enzymes (Streptozymes)]. Using 100 sera randomly selected, the clinical characteristis of which were known, we compared two methods of rapid detection of streptococcal infections by slide agglutination. One was the classical latex test for detection of anti-streptolysin O, the other was the streptozyme test. The latter reagent detects the presence of 5 streptococcal antibodies, anti-streptolysin O, anti-streptokinase, anti-streptohyaluronidase, anti-desoxyribonuclease and anti-nicotinamide-adenine-dinucleotidase. It was found to be more sensitive than the latex test, for antistreptolysin O. Estimations of A.S.K. and A.S.H. confirmed also the greater specificity of the streptozyme test and showed that, thanks to the presence of supplementary enzymes, it may be positive earlier than the A.S.O. latex test. Finally, used as a semi-quantitative method, streptozyme is useful to follow up approximately in the laboratory, the course of streptococcal infections."} {"id": "PMID:170576", "title": "Infectious mononucleosis: histopathologic aspects.", "content": "The main histopathologic features of infectious mononucleosis are described. In the lymph nodes, the principal change is the appearance of numerous large pyroninophilic cells (immunoblasts), initially expanding the paracortical zone but later extending throughout the node. Similar, large lymphoid cells appear as infiltrates in many other organs and tissues. Cells morphologically similar to Sternberg-Reed cells may be found in the lymph nodes of patients with infectious mononucleosis and other conditions apart from Hodgkin's disease. The diagnostic importance of considering not only the Sternberg-Reed cells but their milieu is stressed. A possible relationship between infectious mononucleosis and lymphoreticular malignancy is suggested by a number of observations, but a definite etiologic link is yet to be established.", "contents": "Infectious mononucleosis: histopathologic aspects. The main histopathologic features of infectious mononucleosis are described. In the lymph nodes, the principal change is the appearance of numerous large pyroninophilic cells (immunoblasts), initially expanding the paracortical zone but later extending throughout the node. Similar, large lymphoid cells appear as infiltrates in many other organs and tissues. Cells morphologically similar to Sternberg-Reed cells may be found in the lymph nodes of patients with infectious mononucleosis and other conditions apart from Hodgkin's disease. The diagnostic importance of considering not only the Sternberg-Reed cells but their milieu is stressed. A possible relationship between infectious mononucleosis and lymphoreticular malignancy is suggested by a number of observations, but a definite etiologic link is yet to be established."} {"id": "PMID:170578", "title": "The ultrastructure of smooth muscle tumors with a consideration of the possible relationship of glomangiomas, hemangiopericytomas, and cardiac myxomas.", "content": "Tumors classified as being of smooth muscle origin by light microscopy were studied with the electron microscope. Their ultrastructure verified the diagnosis in all of the seven leiomyomas but in only eight of the twelve (66 percent) tumors that were finally classified as leiomyosarcoma. The discrepancy of the light microscopic and ultrastructural findings in these four sarcomas may be due to sampling problems likely to be encountered in poorly differentiated tumors or simply the failure of development of specific ultrastructural features in the face of a characteristic growth pattern at the light microscopic level. Among other tumors that have been considered to be of smooth muscle origin--hemangiopericytoma, glomangioma, and cardiac myxoma--only the glomangioma showed ultrastructure features identical to those of smooth muscle.", "contents": "The ultrastructure of smooth muscle tumors with a consideration of the possible relationship of glomangiomas, hemangiopericytomas, and cardiac myxomas. Tumors classified as being of smooth muscle origin by light microscopy were studied with the electron microscope. Their ultrastructure verified the diagnosis in all of the seven leiomyomas but in only eight of the twelve (66 percent) tumors that were finally classified as leiomyosarcoma. The discrepancy of the light microscopic and ultrastructural findings in these four sarcomas may be due to sampling problems likely to be encountered in poorly differentiated tumors or simply the failure of development of specific ultrastructural features in the face of a characteristic growth pattern at the light microscopic level. Among other tumors that have been considered to be of smooth muscle origin--hemangiopericytoma, glomangioma, and cardiac myxoma--only the glomangioma showed ultrastructure features identical to those of smooth muscle."} {"id": "PMID:170585", "title": "[Poly-epiphyseal dysplasia, probably autosomal recessive. Contribution of the ultrastructural study to the discovery of this autonomous form].", "content": "An ultrastructural study of growth cartilage permitted individualization of a particular form of polyepiphyseal dysplasia which differs clinically and radiologically only slightly from the dominant form. The main difference concerns the superior femoral epiphyses which are more flattened and spread out. Inclusions, probably of lysosomial origin and containing granulous or filamentous material, were observed. This aspect is different from that observed in the dominant form and consisting of swellings of the endoplasmic reticulum with a suggestion of a periodical structure. The mode of inheritance could not be firmly demonstrated. Some degree of consanguinity of the second patient's parents favours an autosomal recessive inheritance.", "contents": "[Poly-epiphyseal dysplasia, probably autosomal recessive. Contribution of the ultrastructural study to the discovery of this autonomous form]. An ultrastructural study of growth cartilage permitted individualization of a particular form of polyepiphyseal dysplasia which differs clinically and radiologically only slightly from the dominant form. The main difference concerns the superior femoral epiphyses which are more flattened and spread out. Inclusions, probably of lysosomial origin and containing granulous or filamentous material, were observed. This aspect is different from that observed in the dominant form and consisting of swellings of the endoplasmic reticulum with a suggestion of a periodical structure. The mode of inheritance could not be firmly demonstrated. Some degree of consanguinity of the second patient's parents favours an autosomal recessive inheritance."} {"id": "PMID:170590", "title": "Angioscintiphotography with 99mTc in 310 cases of space-occupying kidney lesions.", "content": "Angioscintiphotography with 99mTc has been performed in 310 cases of space-occupying kidney lesions with the purpose of establishing the diagnostic value of the kidney perfusion. In the presence of a neoplasm, a more or less marked blood flow in the lesion generally appears as a hot area. This pattern is not observed in poor vascularized carcinomas or in Wilms' tumors. The percentage of poorly vascularized tumors is moderate and does not affect the value of the method. Cystic lesions appear usually to be cold. Large cysts exhibit no uptake; on the contrary, the degree of vascularization in the small cysts is more difficult to evaluate, as the normally supplied surrounding parenchyma overlaps the cold area caused by the cyst. In the evaluation of the angioscintiphotographic picture, we must take into account the concomitant hepatic or splenic vascularization, which may cause some doubts of interpretation because of projection interferences. The renal angioscintiphotography has an important rule in specifying the nature of a space-occupying kidney lesion and may be regarded as a useful screening test.", "contents": "Angioscintiphotography with 99mTc in 310 cases of space-occupying kidney lesions. Angioscintiphotography with 99mTc has been performed in 310 cases of space-occupying kidney lesions with the purpose of establishing the diagnostic value of the kidney perfusion. In the presence of a neoplasm, a more or less marked blood flow in the lesion generally appears as a hot area. This pattern is not observed in poor vascularized carcinomas or in Wilms' tumors. The percentage of poorly vascularized tumors is moderate and does not affect the value of the method. Cystic lesions appear usually to be cold. Large cysts exhibit no uptake; on the contrary, the degree of vascularization in the small cysts is more difficult to evaluate, as the normally supplied surrounding parenchyma overlaps the cold area caused by the cyst. In the evaluation of the angioscintiphotographic picture, we must take into account the concomitant hepatic or splenic vascularization, which may cause some doubts of interpretation because of projection interferences. The renal angioscintiphotography has an important rule in specifying the nature of a space-occupying kidney lesion and may be regarded as a useful screening test."} {"id": "PMID:170591", "title": "A precise chromatography system for specific technetium-99m radiopharmaceuticals.", "content": "New chromatographic procedures are needed to accurately determine the radiochemical purity of technetium-99m labeled radiopharmaceuticals. A chromatography system has been developed for technetium-99m diethylenetriaminepentacetic acid, technetium-99m diphosphonate, and technetium-99m pyrophosphate. The technique involves spotting the radiopharmaceuticals on instant thin layer chromatography-silica gel and developing with acetone (solvent from migrates approximately 12 cm from the origin), air drying, and redeveloping the strip in normal saline (solvent front migrates approximately 6 cm from the origin). The procedure is simple to perform, rapid, accurate, and clearly separates technetium-99m pertechnetate, the technetium-99m radiopharmaceutical, and hydrolyzed reduced technetium-99m. It can be applied in most nuclear medicine laboratories and has the potential to predict the quality of radionuclide images obtained.", "contents": "A precise chromatography system for specific technetium-99m radiopharmaceuticals. New chromatographic procedures are needed to accurately determine the radiochemical purity of technetium-99m labeled radiopharmaceuticals. A chromatography system has been developed for technetium-99m diethylenetriaminepentacetic acid, technetium-99m diphosphonate, and technetium-99m pyrophosphate. The technique involves spotting the radiopharmaceuticals on instant thin layer chromatography-silica gel and developing with acetone (solvent from migrates approximately 12 cm from the origin), air drying, and redeveloping the strip in normal saline (solvent front migrates approximately 6 cm from the origin). The procedure is simple to perform, rapid, accurate, and clearly separates technetium-99m pertechnetate, the technetium-99m radiopharmaceutical, and hydrolyzed reduced technetium-99m. It can be applied in most nuclear medicine laboratories and has the potential to predict the quality of radionuclide images obtained."} {"id": "PMID:170592", "title": "[Concentration of 99mTc-tin-phosphate complexes in soft tissues].", "content": "The concentration of 99mTc-pyrophosphate was determined in the lower extremities of rabbits (normal, abacterial and bacterial affected soft tissues), in osteoarthritis of the hip joint (capsule and muscle) as well as in knee joint effusions. Compared with the 85Sr-concentration, reflecting the calcification capacity, concentrations of 99mTc-pyrophosphate in soft tissues were found to be lower 2 hours p.i., but were up to elevenfold higher 24 hours p.i. These findings should be due to a fixation of 99mTc-pyrophosphate in collagen containing tissues as in the soft tissue tumors (myosarcoma, synvialioma, breast cancer) presented. A mechanism of delayed equilibration could explain augmented uptake in lymph-edema, ascites and effusions in florid osteoarthritis of the knee joint. The possible dependence of 99mTc-pyrophosphate concentration in bone and soft tissue on collagenous contents is discussed.", "contents": "[Concentration of 99mTc-tin-phosphate complexes in soft tissues]. The concentration of 99mTc-pyrophosphate was determined in the lower extremities of rabbits (normal, abacterial and bacterial affected soft tissues), in osteoarthritis of the hip joint (capsule and muscle) as well as in knee joint effusions. Compared with the 85Sr-concentration, reflecting the calcification capacity, concentrations of 99mTc-pyrophosphate in soft tissues were found to be lower 2 hours p.i., but were up to elevenfold higher 24 hours p.i. These findings should be due to a fixation of 99mTc-pyrophosphate in collagen containing tissues as in the soft tissue tumors (myosarcoma, synvialioma, breast cancer) presented. A mechanism of delayed equilibration could explain augmented uptake in lymph-edema, ascites and effusions in florid osteoarthritis of the knee joint. The possible dependence of 99mTc-pyrophosphate concentration in bone and soft tissue on collagenous contents is discussed."} {"id": "PMID:170593", "title": "Rat hepatoma cells nucleolar DNA. 2. Analysis of nucleolar DNA.", "content": "The analysis by CsCl density gradient of nucleolar DNA has revealed that the 1.700 g/cm3 main component can be subdivided in three subcomponents with buoyant densities of 1.707 g/cm3, 1.700 g/cm3, 1.690 g/cm3. The 1.707 g/cm3 and 1.690 g/cm3 components contain all the repetitive sequences which comprise 15 % of the total nucleolar DNA. The ribosomal cistrons are found in components having buoyant density between 1.707 g/cm3 and 1.725 g/gm3. Sodium-p-aminosalicylate-DNA interactions have revealed that only the 1.700 g/cm3 fraction has a destabilized secondary structure. The possible localization of these different fractions on peri and intranucleolar fractions is discussed.", "contents": "Rat hepatoma cells nucleolar DNA. 2. Analysis of nucleolar DNA. The analysis by CsCl density gradient of nucleolar DNA has revealed that the 1.700 g/cm3 main component can be subdivided in three subcomponents with buoyant densities of 1.707 g/cm3, 1.700 g/cm3, 1.690 g/cm3. The 1.707 g/cm3 and 1.690 g/cm3 components contain all the repetitive sequences which comprise 15 % of the total nucleolar DNA. The ribosomal cistrons are found in components having buoyant density between 1.707 g/cm3 and 1.725 g/gm3. Sodium-p-aminosalicylate-DNA interactions have revealed that only the 1.700 g/cm3 fraction has a destabilized secondary structure. The possible localization of these different fractions on peri and intranucleolar fractions is discussed."} {"id": "PMID:170589", "title": "[A cell-line with 27 chromosomes in a human acute leukemia (author's transl)].", "content": "Chromosomal analysis of the bone-marrow aspirate of a five years old girl suffering acute leukemia revealed a cell-line carrying 27 chromosomes. Banding by controlled heating denaturation showed that, in these cells, all chromosomes are haploid, except chromosomes: X, 10, 18, 21. This cell-line, not seen during remission, was found during relapse, in addition to another one with 54 chromosomes. The caryotype of this last clone corresponded to the duplication of the chromosome set found in the first cell-line. The authors discuss two problems: the possible correlations between the clinical evolution and the biological data; the problem raised by the survival and proliferation of such an hypodiploid cell-line.", "contents": "[A cell-line with 27 chromosomes in a human acute leukemia (author's transl)]. Chromosomal analysis of the bone-marrow aspirate of a five years old girl suffering acute leukemia revealed a cell-line carrying 27 chromosomes. Banding by controlled heating denaturation showed that, in these cells, all chromosomes are haploid, except chromosomes: X, 10, 18, 21. This cell-line, not seen during remission, was found during relapse, in addition to another one with 54 chromosomes. The caryotype of this last clone corresponded to the duplication of the chromosome set found in the first cell-line. The authors discuss two problems: the possible correlations between the clinical evolution and the biological data; the problem raised by the survival and proliferation of such an hypodiploid cell-line."} {"id": "PMID:170594", "title": "Rat hepatoma cells nucleolar DNA. II. A possible model of nucleolar DNA organisation.", "content": "A model of nucleolar DNA organization has been established. Three clearly defined main components are found in ascites hepatoma cell nucleolar DNA by CsCl gradient analysis. A linear arrangement for nucleolar DNA and a model of DNA organization in the neighbourhood of a set of ribosomal genes, which may play a fundamental role in the elaboration of nucleolar chromatin tertiary structure, are presented.", "contents": "Rat hepatoma cells nucleolar DNA. II. A possible model of nucleolar DNA organisation. A model of nucleolar DNA organization has been established. Three clearly defined main components are found in ascites hepatoma cell nucleolar DNA by CsCl gradient analysis. A linear arrangement for nucleolar DNA and a model of DNA organization in the neighbourhood of a set of ribosomal genes, which may play a fundamental role in the elaboration of nucleolar chromatin tertiary structure, are presented."} {"id": "PMID:170595", "title": "Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.", "content": "A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9.", "contents": "Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine. A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9."} {"id": "PMID:170596", "title": "Temperature dependence of strand separation of the DNA molecules containing integrated SV40 DNA in transformed cells.", "content": "It has previously been demonstrated that the DNA molecules containing a genetic marker from one region of a bacterial genome undergo complete strand separation at temperatures usually different from the molecules containing a genetic marker from another region of the genome. The experiments also showed that if a group of molecules undergo complete strand separation over a narrow temperature range, of the order of one to three degrees, it is highly likely that they all come from one region of the bacterial genome. The purpose of the work reported here was to establish appropriate procedures for doing a similar analysis of the DNA molecules containing the integrated SV40 DNA in transformed mouse cells. One result of interest is that in the 11A8 cell line about 40 per cent of the integrated SV40 DNA detectable by an RNA-DNA hybridization assay can be accounted for by a group of molecules which undergo complete strand separation within a 1.0 degree C interval.", "contents": "Temperature dependence of strand separation of the DNA molecules containing integrated SV40 DNA in transformed cells. It has previously been demonstrated that the DNA molecules containing a genetic marker from one region of a bacterial genome undergo complete strand separation at temperatures usually different from the molecules containing a genetic marker from another region of the genome. The experiments also showed that if a group of molecules undergo complete strand separation over a narrow temperature range, of the order of one to three degrees, it is highly likely that they all come from one region of the bacterial genome. The purpose of the work reported here was to establish appropriate procedures for doing a similar analysis of the DNA molecules containing the integrated SV40 DNA in transformed mouse cells. One result of interest is that in the 11A8 cell line about 40 per cent of the integrated SV40 DNA detectable by an RNA-DNA hybridization assay can be accounted for by a group of molecules which undergo complete strand separation within a 1.0 degree C interval."} {"id": "PMID:170602", "title": "The preparation of a bacterial collagenase containing negligible non-specific protease activity.", "content": "A three stage procedure for the purification of crude bacterial collagenase is described. The three stages were ion exchange chromatography on SP-Sephadex and DEAE-cellulose, followed by molecular sieve chromatography on Sephadex G-200. The end product was eluted from Sephadex G-200 as a single peak of absorbance at 280 nm, and a single zone of activity against gelatin. The active eluate was divided into two halves, designated fraction 1 and 2 collagenase. Their activities were greater than those of commercially available collagenases when assayed viscometrically against pepsin solubilized collagen from guinea-pig skins. The non-specific protease activities in both fractions were much less than in the commercially available purified collagenases, and fraction 1 collagenase liberated only 2.6% of a [3H]-tryptophan label from a substrate of 2 mg of labelled chick embryo proteins, after an 18 hour incubation. When polymeric collagen was incubated with fraction 1 collagenase, at a final enzyme : substrate ratio of 1:160, the collagen was digested, resulting in the loss of 99.8% hydroxyproline as dialysable material.", "contents": "The preparation of a bacterial collagenase containing negligible non-specific protease activity. A three stage procedure for the purification of crude bacterial collagenase is described. The three stages were ion exchange chromatography on SP-Sephadex and DEAE-cellulose, followed by molecular sieve chromatography on Sephadex G-200. The end product was eluted from Sephadex G-200 as a single peak of absorbance at 280 nm, and a single zone of activity against gelatin. The active eluate was divided into two halves, designated fraction 1 and 2 collagenase. Their activities were greater than those of commercially available collagenases when assayed viscometrically against pepsin solubilized collagen from guinea-pig skins. The non-specific protease activities in both fractions were much less than in the commercially available purified collagenases, and fraction 1 collagenase liberated only 2.6% of a [3H]-tryptophan label from a substrate of 2 mg of labelled chick embryo proteins, after an 18 hour incubation. When polymeric collagen was incubated with fraction 1 collagenase, at a final enzyme : substrate ratio of 1:160, the collagen was digested, resulting in the loss of 99.8% hydroxyproline as dialysable material."} {"id": "PMID:170603", "title": "Transformation by polyoma virus alters expression of a cell mutation affecting cycle traverse.", "content": "A temperature-sensitive mutant of hamster BHK 21/13 cells, tsAF8, which at 39 degrees becomes arrested in the G1 (G0) phase of the cell cycle, is phenotypically altered with respect to temperature sensitivity after transformation with polyoma virus. Polyoma transformation does not produce reversion to a non-temperature-sensitive phenotype but causes increased entry into S and increased rate of cell death at the nonpermissive temperature, compared to untransformed tsAF8 cells. The increased frequency of cells synthesizing DNA is not accompanied by an increased frequency of mitosis, since most of the polyoma-transformed tsAF8 cells that synthesize DNA at the nonpermissive temperature do not divide. At the permissive temperature, polyoma-transformed tsAF8 cells, unlike tsAF8, also lose viability when exposed to other methods of arresting cells in G1. The most likely explanation for this phenomenon is that polyoma virus transformation interferes with the cellular response to this mutation as well as to other conditions that cause cell cycle arrest in G1.", "contents": "Transformation by polyoma virus alters expression of a cell mutation affecting cycle traverse. A temperature-sensitive mutant of hamster BHK 21/13 cells, tsAF8, which at 39 degrees becomes arrested in the G1 (G0) phase of the cell cycle, is phenotypically altered with respect to temperature sensitivity after transformation with polyoma virus. Polyoma transformation does not produce reversion to a non-temperature-sensitive phenotype but causes increased entry into S and increased rate of cell death at the nonpermissive temperature, compared to untransformed tsAF8 cells. The increased frequency of cells synthesizing DNA is not accompanied by an increased frequency of mitosis, since most of the polyoma-transformed tsAF8 cells that synthesize DNA at the nonpermissive temperature do not divide. At the permissive temperature, polyoma-transformed tsAF8 cells, unlike tsAF8, also lose viability when exposed to other methods of arresting cells in G1. The most likely explanation for this phenomenon is that polyoma virus transformation interferes with the cellular response to this mutation as well as to other conditions that cause cell cycle arrest in G1."} {"id": "PMID:170604", "title": "Coupled in vitro transcription and translation of vesicular stomatitis virus messenger RNA.", "content": "The virion transcriptase (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) of vesicular stomatitis virus was fully active when ribonucleoprotein cores from purified virions were added to cell-free protein synthesizing systems of eukaryotic origin. Synthesis of mRNA was linear for at least 3 hr and the newly synthesized viral mRNA was efficiently utilized for the synthesis of viral proteins N (nucleoprotein), NS, and M (matrix); small amounts of a putative G (glycoprotein protein precursor and several unidentified polypeptides were regularly synthesized. The ratio of the various newly synthesized viral proteins was identical after different periods of coupled mRNA and protein synthesis. Identical proteins were obtained when the cell-free protein synthesizing systems were programmed with purified VSV mRNA synthesized in vitro. No detectable L protein was synthesized, even though transcripts complementary to the complete viral genome were detectable in the mRNA preparation by hybridization.", "contents": "Coupled in vitro transcription and translation of vesicular stomatitis virus messenger RNA. The virion transcriptase (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) of vesicular stomatitis virus was fully active when ribonucleoprotein cores from purified virions were added to cell-free protein synthesizing systems of eukaryotic origin. Synthesis of mRNA was linear for at least 3 hr and the newly synthesized viral mRNA was efficiently utilized for the synthesis of viral proteins N (nucleoprotein), NS, and M (matrix); small amounts of a putative G (glycoprotein protein precursor and several unidentified polypeptides were regularly synthesized. The ratio of the various newly synthesized viral proteins was identical after different periods of coupled mRNA and protein synthesis. Identical proteins were obtained when the cell-free protein synthesizing systems were programmed with purified VSV mRNA synthesized in vitro. No detectable L protein was synthesized, even though transcripts complementary to the complete viral genome were detectable in the mRNA preparation by hybridization."} {"id": "PMID:170605", "title": "Characterization of purified DNA-relaxing enzyme from human tissue culture cells.", "content": "Superhelical simian virus 40 DNA migrates more rapidly during electrophoresis in agarose gels than covalently closed DNA free of superhelical turns (relaxed DNA). The difference in electrophoretic mobility between superhelical and relaxed DNA was used to monitor the activity of a protein from human tissue culture cells which converts superhelical DNA into relaxed DNA. Purified DNA-relaxing protein removes both negative and positive superhelical turns and acts in a catalytic manner. The relaxation of DNA proceeds in a stepwise fashion and DNA intermediates with decreasing numbers of superhelical turns are seen during the course of the reaction.", "contents": "Characterization of purified DNA-relaxing enzyme from human tissue culture cells. Superhelical simian virus 40 DNA migrates more rapidly during electrophoresis in agarose gels than covalently closed DNA free of superhelical turns (relaxed DNA). The difference in electrophoretic mobility between superhelical and relaxed DNA was used to monitor the activity of a protein from human tissue culture cells which converts superhelical DNA into relaxed DNA. Purified DNA-relaxing protein removes both negative and positive superhelical turns and acts in a catalytic manner. The relaxation of DNA proceeds in a stepwise fashion and DNA intermediates with decreasing numbers of superhelical turns are seen during the course of the reaction."} {"id": "PMID:170606", "title": "Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40.", "content": "A number of hybridization techniques have been used to assess the homology between the genomes of BK virus (BKV) and simian virus 40 (SV40). A noncontiguous set of homologous sequences has been localized primarily within the late region of the SV40 genome, and these sequences presumably account for the cross-reaction between V-antigens of the two viruses. The reason for the relatively strong crossreaction between SV40 and BKV T-antigens is still unclear. The sequence homology and similarity in genomic organization suggest a close relationship between these papovaviruses.", "contents": "Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40. A number of hybridization techniques have been used to assess the homology between the genomes of BK virus (BKV) and simian virus 40 (SV40). A noncontiguous set of homologous sequences has been localized primarily within the late region of the SV40 genome, and these sequences presumably account for the cross-reaction between V-antigens of the two viruses. The reason for the relatively strong crossreaction between SV40 and BKV T-antigens is still unclear. The sequence homology and similarity in genomic organization suggest a close relationship between these papovaviruses."} {"id": "PMID:170607", "title": "RNAs of simian virus 40 in productively infected monkey cells: kinetics of formation and decay in enucleate cells.", "content": "We demonstrate here the usefulness of cytochalasin B enucleate cells for the study of the metabolism of cytoplasmic mRNA and for determining its half-life in animal cells. Simian virus 40 infected monkey cells in which the RNA had been labeled with [3H]uridine were enucleated, and the decay of the two prominent RNAs of simian virus 40, the 19S and 16S species, was measured by analysis on sucrose gradients. The results of these experiments, together with kinetic analysis of nuclear and cytoplasmic viral RNA, indicate a precursor-product relationship between the 19S and 16S cytoplasmic viral RNA species, which decay by first-order kinetics with a mean half-life of about 3 hr and 6 hr, respectively.", "contents": "RNAs of simian virus 40 in productively infected monkey cells: kinetics of formation and decay in enucleate cells. We demonstrate here the usefulness of cytochalasin B enucleate cells for the study of the metabolism of cytoplasmic mRNA and for determining its half-life in animal cells. Simian virus 40 infected monkey cells in which the RNA had been labeled with [3H]uridine were enucleated, and the decay of the two prominent RNAs of simian virus 40, the 19S and 16S species, was measured by analysis on sucrose gradients. The results of these experiments, together with kinetic analysis of nuclear and cytoplasmic viral RNA, indicate a precursor-product relationship between the 19S and 16S cytoplasmic viral RNA species, which decay by first-order kinetics with a mean half-life of about 3 hr and 6 hr, respectively."} {"id": "PMID:170608", "title": "Interaction of f1 histone with superhelical DNA.", "content": "The superhelicity of double-stranded, closed circular SV40 DNA was altered by the addition of various amounts of ethidium bromide. The interaction of f1 histone with the series of molecules of various superhelicities was studied. The extent of interaction increases with increasing superhelicity regardless of whether it is of the positive or negative sense. The interaction of f1 histone with superhelical DNA is shown to be reversible.", "contents": "Interaction of f1 histone with superhelical DNA. The superhelicity of double-stranded, closed circular SV40 DNA was altered by the addition of various amounts of ethidium bromide. The interaction of f1 histone with the series of molecules of various superhelicities was studied. The extent of interaction increases with increasing superhelicity regardless of whether it is of the positive or negative sense. The interaction of f1 histone with superhelical DNA is shown to be reversible."} {"id": "PMID:170609", "title": "Separation of \"estrogen-induced\" protein from phosphoprotein phosphatase activity of immature rat uterus.", "content": "Preparations of the \"induced protein\" which appears in the rat uterus within 40 min of estradiol administration have recently been reported to contain phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) activity. We found that these two proteins distribute differently on ammonium sulfate fractionation of uterine cytosol. Preparative cellulose acetate electrophoresis afforded complete (greater than 99.9%) separation of phosphoprotein phosphatase activity from the induced protein. The specific activity of phosphoprotein phosphatase in uterine cytosol was unchanged 1, 4, 12, or 24 hr after estradiol administration. These results are incompatible with the view that the induced protein mediates estrogen action by virtue of an inherent phosphoprotein phosphatase activity.", "contents": "Separation of \"estrogen-induced\" protein from phosphoprotein phosphatase activity of immature rat uterus. Preparations of the \"induced protein\" which appears in the rat uterus within 40 min of estradiol administration have recently been reported to contain phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) activity. We found that these two proteins distribute differently on ammonium sulfate fractionation of uterine cytosol. Preparative cellulose acetate electrophoresis afforded complete (greater than 99.9%) separation of phosphoprotein phosphatase activity from the induced protein. The specific activity of phosphoprotein phosphatase in uterine cytosol was unchanged 1, 4, 12, or 24 hr after estradiol administration. These results are incompatible with the view that the induced protein mediates estrogen action by virtue of an inherent phosphoprotein phosphatase activity."} {"id": "PMID:170610", "title": "Association of mouse liver adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels with histocompatibility-2 genotype.", "content": "When the content of cyclic AMP (cAMP) was compared in livers of a series of congenic mouse strains differing at the H-2 locus, significant variation in concentration of cAMP per unit wet weight was found among strains, and also for animals of a given strain with increasing age. For a given age, from 8 to 22 weeks, cAMP levels in liver of H-2a and H-2b genotype animals were significantly higher than that in liver of H-2k type animals. This difference was seen whether the H-2 gene was on the genetic background of strain C57BL/10, C3H, or A. Levels of cAMP in livers of H-2d animals were between those of H-2a and H-2k animals.", "contents": "Association of mouse liver adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels with histocompatibility-2 genotype. When the content of cyclic AMP (cAMP) was compared in livers of a series of congenic mouse strains differing at the H-2 locus, significant variation in concentration of cAMP per unit wet weight was found among strains, and also for animals of a given strain with increasing age. For a given age, from 8 to 22 weeks, cAMP levels in liver of H-2a and H-2b genotype animals were significantly higher than that in liver of H-2k type animals. This difference was seen whether the H-2 gene was on the genetic background of strain C57BL/10, C3H, or A. Levels of cAMP in livers of H-2d animals were between those of H-2a and H-2k animals."} {"id": "PMID:170611", "title": "Relationship of the first step in protein synthesis to ppGpp: formation of A(5')ppp(5')Gpp.", "content": "In the presence of purified Escherichia coli lysyl-tRNA synthetase [L-lysine:tRNALys ligase (AMP-forming) EC 6.1.1.6], L-lysine, and ATP, addition of the nucleotide ppGpp results in formation of a unique product-A(5')ppp(5') Gpp. The same compound is also formed very rapidly in a cell-free protein-synthesizing system when ppGpp is added. The possible significance of this reaction in the rapid turnover of ppGpp and as a more general mechanism by which an AMP residue is activated and introduced onto a 5'-diphosphorylated species, including the 5'-end of an RNA, is further discussed.", "contents": "Relationship of the first step in protein synthesis to ppGpp: formation of A(5')ppp(5')Gpp. In the presence of purified Escherichia coli lysyl-tRNA synthetase [L-lysine:tRNALys ligase (AMP-forming) EC 6.1.1.6], L-lysine, and ATP, addition of the nucleotide ppGpp results in formation of a unique product-A(5')ppp(5') Gpp. The same compound is also formed very rapidly in a cell-free protein-synthesizing system when ppGpp is added. The possible significance of this reaction in the rapid turnover of ppGpp and as a more general mechanism by which an AMP residue is activated and introduced onto a 5'-diphosphorylated species, including the 5'-end of an RNA, is further discussed."} {"id": "PMID:170612", "title": "Solid tumor models for the assessment of different treatment modalities: I. Radiation-induced changes in growth rate characteristics of a solid tumor model.", "content": "A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate data from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can be obtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided all of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors.", "contents": "Solid tumor models for the assessment of different treatment modalities: I. Radiation-induced changes in growth rate characteristics of a solid tumor model. A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate data from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can be obtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided all of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors."} {"id": "PMID:170613", "title": "Follicle-stimulating hormone stimulates estradiol-17beta synthesis in cultured Sertoli cells.", "content": "Sertoli cells isolated from testes of 20-day-old rats and maintained in primary culture synthesized estradiol-17beta [1,3,5(10)-estratriene-3,17beta-diol] (measured by specific radioimmunoassay) when testosterone (17beta-hydroxy-4-androsten-3-one) 0.5 muM, was added to the culture medium. No detectable estradiol synthesis occurred when cells were incubated in medium containing pregnenolone (3beta-hydroxypregn-5-en-20-one), 0.5 muM, or containing no added steroid substrate. Follicle-stimulating hormone (FSH) (NIH-FSH-S10, 5 mug/ml) stimulated estradiol synthesis 12- to 80-fold when added to medium containing testosterone, but not when added to medium containing pregnenolone or no exogenous steroid substrate. A highly purified FSH preparation, with FSH potency 50 times that of the NIH-FSH, caused a similar stimulation at a concentration of 0.25 mug/ml of medium, whereas luteinizing hormone (NIH-LH-S18, 5 MUG/ML) Caused only marginal stimulation. Dibutyryl-adenosine 3':5' cyclic monophosphate, 0.1 mM, caused a 30-fold increase in estradiol synthesis by Sertoli cells cultured in medium containing testosterone. These studies provide direct demonstration of estradiol-17beta production by Seroli cells from normal animals, and offer evidence that the synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and adenosine 3':5' cyclic monophosphate.", "contents": "Follicle-stimulating hormone stimulates estradiol-17beta synthesis in cultured Sertoli cells. Sertoli cells isolated from testes of 20-day-old rats and maintained in primary culture synthesized estradiol-17beta [1,3,5(10)-estratriene-3,17beta-diol] (measured by specific radioimmunoassay) when testosterone (17beta-hydroxy-4-androsten-3-one) 0.5 muM, was added to the culture medium. No detectable estradiol synthesis occurred when cells were incubated in medium containing pregnenolone (3beta-hydroxypregn-5-en-20-one), 0.5 muM, or containing no added steroid substrate. Follicle-stimulating hormone (FSH) (NIH-FSH-S10, 5 mug/ml) stimulated estradiol synthesis 12- to 80-fold when added to medium containing testosterone, but not when added to medium containing pregnenolone or no exogenous steroid substrate. A highly purified FSH preparation, with FSH potency 50 times that of the NIH-FSH, caused a similar stimulation at a concentration of 0.25 mug/ml of medium, whereas luteinizing hormone (NIH-LH-S18, 5 MUG/ML) Caused only marginal stimulation. Dibutyryl-adenosine 3':5' cyclic monophosphate, 0.1 mM, caused a 30-fold increase in estradiol synthesis by Sertoli cells cultured in medium containing testosterone. These studies provide direct demonstration of estradiol-17beta production by Seroli cells from normal animals, and offer evidence that the synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and adenosine 3':5' cyclic monophosphate."} {"id": "PMID:170614", "title": "Appearance of smaller mannosyl-glycopeptides on the surface of a human cell transformed by simian virus 40.", "content": "When fucosyl surface glycopeptides from growing normal human cells (WI 38) were compared with those derived from nongrowing cells the former were enriched in high-molecular-weight species. However, a line of human cells (WI 18Va) transformed by simian virus 40 appeared to have fucosyl-glycopeptides similar in size distribution to those from rapidly growing non-transformed cells (WI 38). I propose that the enrichment in high molecular weight species in these cells might be growth- rather than transformation-dependent. Using radioactive mannose to label surface glycopeptides, I observed that those derived from transformed cells (WI 18Va) were smaller than those from rapidly growing normal cells. Thus differences in size distribution may not be adequate criteria to evaluate the growth-dependent alterations in cell surface glycopeptides.", "contents": "Appearance of smaller mannosyl-glycopeptides on the surface of a human cell transformed by simian virus 40. When fucosyl surface glycopeptides from growing normal human cells (WI 38) were compared with those derived from nongrowing cells the former were enriched in high-molecular-weight species. However, a line of human cells (WI 18Va) transformed by simian virus 40 appeared to have fucosyl-glycopeptides similar in size distribution to those from rapidly growing non-transformed cells (WI 38). I propose that the enrichment in high molecular weight species in these cells might be growth- rather than transformation-dependent. Using radioactive mannose to label surface glycopeptides, I observed that those derived from transformed cells (WI 18Va) were smaller than those from rapidly growing normal cells. Thus differences in size distribution may not be adequate criteria to evaluate the growth-dependent alterations in cell surface glycopeptides."} {"id": "PMID:170615", "title": "New histones found in mature mammalian testes.", "content": "Two new histones have been found in sexually mature testes of several mammals. The new histones have been identified as a new F1 (TF1) and F2b (TF2b) on the basis of their behavior upon chemical fractionation procedures and electrophoresis at several urea concentrations. The new testis-specific histones are absent in very immature animals and in somatic tissues. However, by day 20, in the rat, the histone pattern is that of the adult, displaying nearly a full complement of TF1 and TF2b. The new histone complement evidently is characteristic of prespermatid germ cells. The degree of evolutionary variations in these histones and in other basic sperm proteins, as detected by change in electrophoretic mobility, appears to be much greater than that seen in somatic histones.", "contents": "New histones found in mature mammalian testes. Two new histones have been found in sexually mature testes of several mammals. The new histones have been identified as a new F1 (TF1) and F2b (TF2b) on the basis of their behavior upon chemical fractionation procedures and electrophoresis at several urea concentrations. The new testis-specific histones are absent in very immature animals and in somatic tissues. However, by day 20, in the rat, the histone pattern is that of the adult, displaying nearly a full complement of TF1 and TF2b. The new histone complement evidently is characteristic of prespermatid germ cells. The degree of evolutionary variations in these histones and in other basic sperm proteins, as detected by change in electrophoretic mobility, appears to be much greater than that seen in somatic histones."} {"id": "PMID:170616", "title": "Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F2alpha.", "content": "Prostaglandin (PG) F2alpha added to quiescent Swiss mouse 3T3 cell cultures initiates DNA synthesis and cell proliferation in a small proportion of the cells. Insulin, which markedly potentiates the effect of PGF2alpha on the initiation of cell division when added with PGF2alpha, causes a simultaneous reduction in intracellular cyclic AMP and an increase in cyclic GMP concentrations similar to those observed after serum addition. Prostaglandins E1 and E2 are less effective than PGF2alpha in initiating DNA synthesis and this effect is only observed at higher concentrations. Therefore, some prostaglandins can act as extracellular factors to regulate cell proliferation.", "contents": "Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F2alpha. Prostaglandin (PG) F2alpha added to quiescent Swiss mouse 3T3 cell cultures initiates DNA synthesis and cell proliferation in a small proportion of the cells. Insulin, which markedly potentiates the effect of PGF2alpha on the initiation of cell division when added with PGF2alpha, causes a simultaneous reduction in intracellular cyclic AMP and an increase in cyclic GMP concentrations similar to those observed after serum addition. Prostaglandins E1 and E2 are less effective than PGF2alpha in initiating DNA synthesis and this effect is only observed at higher concentrations. Therefore, some prostaglandins can act as extracellular factors to regulate cell proliferation."} {"id": "PMID:170620", "title": "Transmission of human leukaemia to nonhuman primates.", "content": "The experiments described show that inoculation of two monkey species, M. arctoides and P. hamadryas, with human leukaemic blood or its filtrates causes a viral disease with the characteristics of malignant lymphoma of mixed type. The disease was passed in subsequent passages. The virus was isolated and identified as an oncornavirus of C-type by its characteristic morphological appearance and buoyant density (1.16 g/cm3 in sucrose and 1.21 g/cm3 in caesium chloride), and by the presence of 60-70S RNA and RNA-dependent DNA polymerase. There is some evidence that it differs immunologically from other known oncornaviruses of mammals including primates. It is postulated that both horizontal and vertical transmission of this oncornavirus can occur.", "contents": "Transmission of human leukaemia to nonhuman primates. The experiments described show that inoculation of two monkey species, M. arctoides and P. hamadryas, with human leukaemic blood or its filtrates causes a viral disease with the characteristics of malignant lymphoma of mixed type. The disease was passed in subsequent passages. The virus was isolated and identified as an oncornavirus of C-type by its characteristic morphological appearance and buoyant density (1.16 g/cm3 in sucrose and 1.21 g/cm3 in caesium chloride), and by the presence of 60-70S RNA and RNA-dependent DNA polymerase. There is some evidence that it differs immunologically from other known oncornaviruses of mammals including primates. It is postulated that both horizontal and vertical transmission of this oncornavirus can occur."} {"id": "PMID:170622", "title": "Splenocyte plaque assay for the detection of murine leukemia virus.", "content": "A modified XC assay for murine leukemia virus (MuLV) employing splenocytes taken directly from the animal is described. This modification can be more than 1000 times more sensitive than XC plaque assays employing tissue extracts. This technique should lend itself readily to the quantitation of infectious MuLV in defined populations of lymphoid cells.", "contents": "Splenocyte plaque assay for the detection of murine leukemia virus. A modified XC assay for murine leukemia virus (MuLV) employing splenocytes taken directly from the animal is described. This modification can be more than 1000 times more sensitive than XC plaque assays employing tissue extracts. This technique should lend itself readily to the quantitation of infectious MuLV in defined populations of lymphoid cells."} {"id": "PMID:170623", "title": "Transplatation resistance to adenovirus-induced hepatocellular carcinomas.", "content": "Two transplantable hepatic carcinomas of the hamster contained CELO virus-induced TSTA, confirming the etiological role of this avian adenovirus in the induction of hepatic tumors. Transplantation resistnace could not be induced with oncogenic adenoviruses of human, simian, or canine origin.", "contents": "Transplatation resistance to adenovirus-induced hepatocellular carcinomas. Two transplantable hepatic carcinomas of the hamster contained CELO virus-induced TSTA, confirming the etiological role of this avian adenovirus in the induction of hepatic tumors. Transplantation resistnace could not be induced with oncogenic adenoviruses of human, simian, or canine origin."} {"id": "PMID:170624", "title": "Concerning the subcellular distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the rat adrenal.", "content": "The distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the subcellular fractions of rat adrenal gland has been determined. Based on the total activity found, 55% was in the microsomal fraction, 10% in the heavy-mitochondrial fraction, 3% in the light-mitochondrial fraction and 26% in the fraction consisting of cell-debris plus nuclei. Ninety-five percent of the total activity was recovered in the fractions. Approximately half the activity in the heavy-mitochondrial fraction could be accounted for by microsomal contamination.", "contents": "Concerning the subcellular distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the rat adrenal. The distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the subcellular fractions of rat adrenal gland has been determined. Based on the total activity found, 55% was in the microsomal fraction, 10% in the heavy-mitochondrial fraction, 3% in the light-mitochondrial fraction and 26% in the fraction consisting of cell-debris plus nuclei. Ninety-five percent of the total activity was recovered in the fractions. Approximately half the activity in the heavy-mitochondrial fraction could be accounted for by microsomal contamination."} {"id": "PMID:170625", "title": "Antibody titers by mixed agglutination to varicella-zoster, herpes simplex and vaccinia viruses in patients with multiple sclerosis.", "content": "Antibody titers to varicella-zoster (V-Z), herpes simplex (HSV) and vaccinia viruses were determined in sera collected in Buffalo, NY, from patients with multiple sclerosis (MS), patients with other diseases, and normal individuals. The mixed agglutination test employing cell cultures infected with one of the above viruses as a source of antigen was used to determine antibody titers. The geometric mean titer (GMT) for V-Z in 59 MS cases was significantly higher than that observed in patients with other diseases and in normal individuals. The GMT for vaccinia was also higher in MS patients but the difference was not as great as for V-Z. No difference was observed in the titer of antibodies for HSV. Similar results were obtained for 51 MS patients compared to healthy controls matched for sex and age. Higher antibody titers for V-Z and HSV were observed in cerebrospinal fluids from MS cases than in those from non-MS CNS patients in Baltimore, MD. Antibodies to V-Z, HSV and vaccinia were detected in washing fluids from brain homogenates of MS cases.", "contents": "Antibody titers by mixed agglutination to varicella-zoster, herpes simplex and vaccinia viruses in patients with multiple sclerosis. Antibody titers to varicella-zoster (V-Z), herpes simplex (HSV) and vaccinia viruses were determined in sera collected in Buffalo, NY, from patients with multiple sclerosis (MS), patients with other diseases, and normal individuals. The mixed agglutination test employing cell cultures infected with one of the above viruses as a source of antigen was used to determine antibody titers. The geometric mean titer (GMT) for V-Z in 59 MS cases was significantly higher than that observed in patients with other diseases and in normal individuals. The GMT for vaccinia was also higher in MS patients but the difference was not as great as for V-Z. No difference was observed in the titer of antibodies for HSV. Similar results were obtained for 51 MS patients compared to healthy controls matched for sex and age. Higher antibody titers for V-Z and HSV were observed in cerebrospinal fluids from MS cases than in those from non-MS CNS patients in Baltimore, MD. Antibodies to V-Z, HSV and vaccinia were detected in washing fluids from brain homogenates of MS cases."} {"id": "PMID:170626", "title": "Growth inhibitory and arginase activities in liver and hepatoma extracts.", "content": "The growth-inhibitory activity against H.Ep. No 2 cells observed in phosphate buffer extracts of rat liver appears to be due to the enzyme, arginase. This conclusion is based on the findings that (1) extracts of hepatomas containing lower levels of the enzyme also contain less inhibitory activity; (2) partial purification of the inhibitory factor results in a similar purification of the enzyme; (3) molecular weights of the enzyme and of the inhibitory factor are similar; and (4) various treatments alter the enzyme and inhibitory activities similarly.", "contents": "Growth inhibitory and arginase activities in liver and hepatoma extracts. The growth-inhibitory activity against H.Ep. No 2 cells observed in phosphate buffer extracts of rat liver appears to be due to the enzyme, arginase. This conclusion is based on the findings that (1) extracts of hepatomas containing lower levels of the enzyme also contain less inhibitory activity; (2) partial purification of the inhibitory factor results in a similar purification of the enzyme; (3) molecular weights of the enzyme and of the inhibitory factor are similar; and (4) various treatments alter the enzyme and inhibitory activities similarly."} {"id": "PMID:170627", "title": "Poly (adnenosine diphosphoribose) synthase activity of isolated nuclei of normal and leukemic leukocytes.", "content": "Poly(adenosine diphosphoribose) (ADPR) synthase activities of nuclei isolated from normal human and leukemic leukocytes were assayed by incubation with radioactive NAD+. The synthase activity of leukemic leukocyte nuclei was significantly higher than that of normal leukocyte nuclei. The average length of polymers formed by isolated leukemic nuclei under the prescribed experimental condition ranged from 3.1 to 5.3 ADPR residues per chain, while those produced by normal leukocytes nuclei was 1.7 and 2.6 residues per chain. Isolated leukemic and normal leukocyte nuclei were incubated with and without NAD+ and the ability to carry out DNA synthesis was measured. The endogenous DNA synthesis of NAD-treated and untreated nuclei was the same. This finding parallels the result obtained with Novikoff hepatoma cell nuclei and differs from the observation with rat liver or testis nuclei.", "contents": "Poly (adnenosine diphosphoribose) synthase activity of isolated nuclei of normal and leukemic leukocytes. Poly(adenosine diphosphoribose) (ADPR) synthase activities of nuclei isolated from normal human and leukemic leukocytes were assayed by incubation with radioactive NAD+. The synthase activity of leukemic leukocyte nuclei was significantly higher than that of normal leukocyte nuclei. The average length of polymers formed by isolated leukemic nuclei under the prescribed experimental condition ranged from 3.1 to 5.3 ADPR residues per chain, while those produced by normal leukocytes nuclei was 1.7 and 2.6 residues per chain. Isolated leukemic and normal leukocyte nuclei were incubated with and without NAD+ and the ability to carry out DNA synthesis was measured. The endogenous DNA synthesis of NAD-treated and untreated nuclei was the same. This finding parallels the result obtained with Novikoff hepatoma cell nuclei and differs from the observation with rat liver or testis nuclei."} {"id": "PMID:170634", "title": "A clinical evaluation of a sodium fluoride dentifrice.", "content": "A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05.", "contents": "A clinical evaluation of a sodium fluoride dentifrice. A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05."} {"id": "PMID:170636", "title": "Incubation as a form of psychotherapy in the care of patients in ancient and modern Greece.", "content": "Incubation or temple sleep in sanctuaries of Aesculapius, Amphiaraos, Trophonios, etc., for the care of patients was practised even in the older times of ancient Greece and may be viewed as a form of psychotherapy and especially as 'dream-psychotherapy'. In Greek antiquity, as it is known, dreams were considered as a way of communication between gods and men. Survival of the custom of incubation exists even in our times in modern Greece, but are disappearing slowly. An attempt is made to find an explanation, if any, of those miraculous cures in accordance with the scientific thought of today.", "contents": "Incubation as a form of psychotherapy in the care of patients in ancient and modern Greece. Incubation or temple sleep in sanctuaries of Aesculapius, Amphiaraos, Trophonios, etc., for the care of patients was practised even in the older times of ancient Greece and may be viewed as a form of psychotherapy and especially as 'dream-psychotherapy'. In Greek antiquity, as it is known, dreams were considered as a way of communication between gods and men. Survival of the custom of incubation exists even in our times in modern Greece, but are disappearing slowly. An attempt is made to find an explanation, if any, of those miraculous cures in accordance with the scientific thought of today."} {"id": "PMID:170637", "title": "The use of corticosteroids in the treatment of acute asthma.", "content": "A study of 23 patients admitted to hospital with severe acute asthma is reported in which plasma cortisol level on admission was significantly correlated with the degree of acidaemia and pulse rate. Patients who had not previously received treatment with corticosteroids responded satisfactorily to repeated daily injections of tetracosactrin depot, the rate of improvement being comparable to that observed in other patients treated with intravenous hydrocortisone hemisuccinate. A prompt and sustained rise in plasma cortisol was also seen following tetracosactrin. The total daily dose of hydrocortisone required to achieve plasma cortisol levels above 100 mug/100 ml was less when given by continuous intravenous infusion compared with intermittent injections, and a regime of 3 mg/kg body weight every six hours by infusion appeared satisfactory. Most patients reported subjective improvement by about four hours after starting treatment but objective evidence did not appear until about six hours from the start. Measurements of FEV1 and FVC proved to be the most reliable indices of the beginning of improvement although pulse rate was the first index to show maximum improvement. Previous maintenance treatment with corticosteroids in patients with asthma did not appear materially to affect the plasma half-life of intravenous hydrocortisone (4 mgm/kg body weight) when compared with healthy subjects or other patients with asthma who had not previously been treated with corticosteroids.", "contents": "The use of corticosteroids in the treatment of acute asthma. A study of 23 patients admitted to hospital with severe acute asthma is reported in which plasma cortisol level on admission was significantly correlated with the degree of acidaemia and pulse rate. Patients who had not previously received treatment with corticosteroids responded satisfactorily to repeated daily injections of tetracosactrin depot, the rate of improvement being comparable to that observed in other patients treated with intravenous hydrocortisone hemisuccinate. A prompt and sustained rise in plasma cortisol was also seen following tetracosactrin. The total daily dose of hydrocortisone required to achieve plasma cortisol levels above 100 mug/100 ml was less when given by continuous intravenous infusion compared with intermittent injections, and a regime of 3 mg/kg body weight every six hours by infusion appeared satisfactory. Most patients reported subjective improvement by about four hours after starting treatment but objective evidence did not appear until about six hours from the start. Measurements of FEV1 and FVC proved to be the most reliable indices of the beginning of improvement although pulse rate was the first index to show maximum improvement. Previous maintenance treatment with corticosteroids in patients with asthma did not appear materially to affect the plasma half-life of intravenous hydrocortisone (4 mgm/kg body weight) when compared with healthy subjects or other patients with asthma who had not previously been treated with corticosteroids."} {"id": "PMID:170638", "title": "Non-healing granuloma and the nervous system.", "content": "Three cases of non-healing granuloma with neurological complications are described. One case suffered from Stewart's form of the disease and two from Wegener's variety. The literature is extensively reviewed and the incidence and manner of neurological involvement in 374 cases is discussed. We suggest a classification to indicate four forms of nervous system involvement. First, granulomatous lesions of the central nervous system. Second, vasculitis of the central nervous system. Third, vasculitis of the peripheral nervous system and fourth, infection of the central nervous system. Of all cases 21 per cent had some form of neurological complication. Wegener's type showed more frequent neurological involvement that Stewart's, 26-5 and 12 per cent respectively. Infection of the central nervous system was limited to cases of the Stewart variety.", "contents": "Non-healing granuloma and the nervous system. Three cases of non-healing granuloma with neurological complications are described. One case suffered from Stewart's form of the disease and two from Wegener's variety. The literature is extensively reviewed and the incidence and manner of neurological involvement in 374 cases is discussed. We suggest a classification to indicate four forms of nervous system involvement. First, granulomatous lesions of the central nervous system. Second, vasculitis of the central nervous system. Third, vasculitis of the peripheral nervous system and fourth, infection of the central nervous system. Of all cases 21 per cent had some form of neurological complication. Wegener's type showed more frequent neurological involvement that Stewart's, 26-5 and 12 per cent respectively. Infection of the central nervous system was limited to cases of the Stewart variety."} {"id": "PMID:170639", "title": "Radiologic approach to the pancreas. A decade of progress.", "content": "Radiologic diagnosis of the pancreas has undergone great progress in recent years and several valuable techniques are now available for examining the pancreas. Employed singly or in various combinations, as indicated by the individual patient's clinical and laboratory findings, they make possible an accurate diagnosis of pancreatic disease.", "contents": "Radiologic approach to the pancreas. A decade of progress. Radiologic diagnosis of the pancreas has undergone great progress in recent years and several valuable techniques are now available for examining the pancreas. Employed singly or in various combinations, as indicated by the individual patient's clinical and laboratory findings, they make possible an accurate diagnosis of pancreatic disease."} {"id": "PMID:170640", "title": "Inactive malignant endocrine tumors of the pancreas.", "content": "The angiographic pattern of four non-active endocrine tumors is reported. Three of the tumors were highly vascular and had a characteristic angiographic appearance as observed in a few case reports in the literature. One tumor was angiographically avascular with irregularly scattered calcifications. Similar calcifications in a malignant tumor of the pancreas causing the Zollinger-Ellison syndrome are presented. Hypervascular tumor tissue was observed in the periphery of the calcification. The types of calcification and angiographic characteristics are of diagnostic importance in the differential diagnosis between endocrine tumors and other highly vascular tumors of the pancreas.", "contents": "Inactive malignant endocrine tumors of the pancreas. The angiographic pattern of four non-active endocrine tumors is reported. Three of the tumors were highly vascular and had a characteristic angiographic appearance as observed in a few case reports in the literature. One tumor was angiographically avascular with irregularly scattered calcifications. Similar calcifications in a malignant tumor of the pancreas causing the Zollinger-Ellison syndrome are presented. Hypervascular tumor tissue was observed in the periphery of the calcification. The types of calcification and angiographic characteristics are of diagnostic importance in the differential diagnosis between endocrine tumors and other highly vascular tumors of the pancreas."} {"id": "PMID:170641", "title": "Phlebography of the pancreatic veins.", "content": "Transumbilical and percutaneous transhepatic catheterization is performed of pancreatic veins. The normal phlebographic anatomy is reported together with the findings in patients with carcinoma of the pancreas. Selective catheterization of pancreatic veins with hormone essay for tumor localization is performed in two patients with islet cell tumor of the pancreas. The authors suggest this to be a valuable method in the diagnosis of endocrine tumors of the pancreas.", "contents": "Phlebography of the pancreatic veins. Transumbilical and percutaneous transhepatic catheterization is performed of pancreatic veins. The normal phlebographic anatomy is reported together with the findings in patients with carcinoma of the pancreas. Selective catheterization of pancreatic veins with hormone essay for tumor localization is performed in two patients with islet cell tumor of the pancreas. The authors suggest this to be a valuable method in the diagnosis of endocrine tumors of the pancreas."} {"id": "PMID:170642", "title": "Demonstration of growing casts of hepatocellular carcinoma in the portal vein by celiac angiography: The thread and streaks sign.", "content": "In 9 of 112 patients with hepatocellular carcinoma (HCC) examined by selective celiac and hepatic arteriography, an unusual finding, the \"thread and streaks\" sign, was observed. It began to appear shortly after the start of injection and was most clearly seen at 3.0-3.5 seconds. Histopathologic and radiographic studies of excised livers have demonstrated that these thin streaks correspond to the blood spaces and vessels which run longitudinally in and around a tumor cast growing in a large branch and trunk of the portal vein.", "contents": "Demonstration of growing casts of hepatocellular carcinoma in the portal vein by celiac angiography: The thread and streaks sign. In 9 of 112 patients with hepatocellular carcinoma (HCC) examined by selective celiac and hepatic arteriography, an unusual finding, the \"thread and streaks\" sign, was observed. It began to appear shortly after the start of injection and was most clearly seen at 3.0-3.5 seconds. Histopathologic and radiographic studies of excised livers have demonstrated that these thin streaks correspond to the blood spaces and vessels which run longitudinally in and around a tumor cast growing in a large branch and trunk of the portal vein."} {"id": "PMID:170643", "title": "Selective carotid angiography in the diagnosis of fibrous histiocytoma. A case report.", "content": "Selective carotid angiography is of value in the diagnosis of an orbital fibrous histiocytoma, an uncommon tumor with a high local recurrence rate and frequent distant metastases. The angiogram shows the physical extent of the tumor and also suggests its general microscopic anatomy. Comparison is made with similar angiographic presentations seen in cerebellar hemangioblastomas, glomus tumors, meningiomas, and hemangiopericytomas.", "contents": "Selective carotid angiography in the diagnosis of fibrous histiocytoma. A case report. Selective carotid angiography is of value in the diagnosis of an orbital fibrous histiocytoma, an uncommon tumor with a high local recurrence rate and frequent distant metastases. The angiogram shows the physical extent of the tumor and also suggests its general microscopic anatomy. Comparison is made with similar angiographic presentations seen in cerebellar hemangioblastomas, glomus tumors, meningiomas, and hemangiopericytomas."} {"id": "PMID:170644", "title": "Treatment of locally recurrent carcinoma of the nasopharynx.", "content": "Forty-two patients with recurrent nasopharyngeal carcinoma in the primary site and/or neck nodes were treated at the University of California, San Francisco, between 1940 and 1974. Sixty-nine per cent of the recurrences appeared within 3 years and 83% within 5 years after initial treatment. Retreatment included external radiotherapy and/or intercavitary radium or cobalt beads in the majority of cases. The actuarial survival rate was 41% at 5 years after first recurrence. Survival rates increased proportionally with increasing time between initial treatment and recurrence. There was no statistically significant difference in survival rates with respect to age, sex, race, or histology. Local soft-tissue or bone necrosis developed in 9 patients, but both conditions were tolerated well.", "contents": "Treatment of locally recurrent carcinoma of the nasopharynx. Forty-two patients with recurrent nasopharyngeal carcinoma in the primary site and/or neck nodes were treated at the University of California, San Francisco, between 1940 and 1974. Sixty-nine per cent of the recurrences appeared within 3 years and 83% within 5 years after initial treatment. Retreatment included external radiotherapy and/or intercavitary radium or cobalt beads in the majority of cases. The actuarial survival rate was 41% at 5 years after first recurrence. Survival rates increased proportionally with increasing time between initial treatment and recurrence. There was no statistically significant difference in survival rates with respect to age, sex, race, or histology. Local soft-tissue or bone necrosis developed in 9 patients, but both conditions were tolerated well."} {"id": "PMID:170649", "title": "Effects of arachidonic acid on RNA metabolism in mammary gland explants of mice.", "content": "Arachidonic acid stimulated 3H-uridine incorporation into RNA in mammary gland explants of mice in a manner similar to that of prolactin. The onset of the effects of both prolactin and arachidonic acid occurred following a 2-4 hour lag period. Further, effects of maximally stimulatory concentrations of these agents were nonadditive. Finally, indomethacin abolished the effects of both prolactin and arachidonic acid. A tenable hypothesis to explain these data is that the action of prolactin in the mammary gland may be mediated by an increased availability of arachidonic acid followed by a subsequent enhanced rate of formation of the prostaglandins.", "contents": "Effects of arachidonic acid on RNA metabolism in mammary gland explants of mice. Arachidonic acid stimulated 3H-uridine incorporation into RNA in mammary gland explants of mice in a manner similar to that of prolactin. The onset of the effects of both prolactin and arachidonic acid occurred following a 2-4 hour lag period. Further, effects of maximally stimulatory concentrations of these agents were nonadditive. Finally, indomethacin abolished the effects of both prolactin and arachidonic acid. A tenable hypothesis to explain these data is that the action of prolactin in the mammary gland may be mediated by an increased availability of arachidonic acid followed by a subsequent enhanced rate of formation of the prostaglandins."} {"id": "PMID:170652", "title": "Effect of antithymocyte serum of murine cytomegalovirus emcephalitis in weanling mice.", "content": "The symptomatology and histopathological picture were studied in weanling mice inoculated intracerebrally with MCMV and treated with ATS. Increased mortality was observed and fatal encephalopathy developed. Lesions in the brain included areas of necrosis with neuronal degeneration without marked inflammatory cell response until the 21st day after infection. In contrast, the brain of mice inoculated with virus alone or with virus and treated with NSH showed perivascular cuffs and focal infiltration with little or no evidence of loss of neurons. These observations suggest that the degenerative lesions in the brain are directly related to virus multiplication and that the inflammatory response is beneficial rather than detrimental.", "contents": "Effect of antithymocyte serum of murine cytomegalovirus emcephalitis in weanling mice. The symptomatology and histopathological picture were studied in weanling mice inoculated intracerebrally with MCMV and treated with ATS. Increased mortality was observed and fatal encephalopathy developed. Lesions in the brain included areas of necrosis with neuronal degeneration without marked inflammatory cell response until the 21st day after infection. In contrast, the brain of mice inoculated with virus alone or with virus and treated with NSH showed perivascular cuffs and focal infiltration with little or no evidence of loss of neurons. These observations suggest that the degenerative lesions in the brain are directly related to virus multiplication and that the inflammatory response is beneficial rather than detrimental."} {"id": "PMID:170662", "title": "[Value and limitatious of scintigraphy of the sacro-iliac joints using technetium pyrophosphate].", "content": "Scintigraphic exploration of the sacroiliac (S.I.) joints by 99 m-technetium pyrophosphate is simple and free of all danger. The fixation of the isotope in the right sacroiliac (R.S.I.) and the \"normal\" limits of the fixation ratios R.S.I./L.R. and the lumbar rachis (L.R.), visible on the same film. A series of 28 controls having made it possible to calculate the \"normal\" limits of the fixation ratios R.S.I./L.R. and L.S.I./L.R., the isotopic fixation was measured in 25 patients with sacroiliac inflammation, 21 of whom were rheumatic, 3 infectious. It was shown that scintigraphy could yield useful information on the evolution of sacroiliac inflammation, making an early diagnosis possible, and also contributing to differentiation between rheumatic and infectious inflammation.", "contents": "[Value and limitatious of scintigraphy of the sacro-iliac joints using technetium pyrophosphate]. Scintigraphic exploration of the sacroiliac (S.I.) joints by 99 m-technetium pyrophosphate is simple and free of all danger. The fixation of the isotope in the right sacroiliac (R.S.I.) and the \"normal\" limits of the fixation ratios R.S.I./L.R. and the lumbar rachis (L.R.), visible on the same film. A series of 28 controls having made it possible to calculate the \"normal\" limits of the fixation ratios R.S.I./L.R. and L.S.I./L.R., the isotopic fixation was measured in 25 patients with sacroiliac inflammation, 21 of whom were rheumatic, 3 infectious. It was shown that scintigraphy could yield useful information on the evolution of sacroiliac inflammation, making an early diagnosis possible, and also contributing to differentiation between rheumatic and infectious inflammation."} {"id": "PMID:170666", "title": "Trypsin activation of latent collagenase from several mammalian sources.", "content": "Latent collagenase, subject to activation by trypsin, was found in culture fluids of cells and tissues from several mammalian sources. The activation requires exposure to enzymatically active trypsin and cannot be achieved by inhibited or by heat-inactivated trypsin.", "contents": "Trypsin activation of latent collagenase from several mammalian sources. Latent collagenase, subject to activation by trypsin, was found in culture fluids of cells and tissues from several mammalian sources. The activation requires exposure to enzymatically active trypsin and cannot be achieved by inhibited or by heat-inactivated trypsin."} {"id": "PMID:170667", "title": "A new case of heavy mu-chain disease.", "content": "The tenth case of mu chain disease is described. The patient lives in Ivory Coast as in our previously reported case. He was not affected with chronic lymphocytic leukaemia and the main clinical feature was liver cirrhosis of unknown origin. The amount of abnormal protein in the serum was great enough to give an abnormal bond on the routine electrophoresis. The protein was devoid of light chains and was present in the form of disulfide linked polymers of incomplete mu chain. The molecular weight of the monomer was approximately 58,000. The protein comprised the Fc fragment and a part of the Fd segment. Bence Jones protein was not found in the urine.", "contents": "A new case of heavy mu-chain disease. The tenth case of mu chain disease is described. The patient lives in Ivory Coast as in our previously reported case. He was not affected with chronic lymphocytic leukaemia and the main clinical feature was liver cirrhosis of unknown origin. The amount of abnormal protein in the serum was great enough to give an abnormal bond on the routine electrophoresis. The protein was devoid of light chains and was present in the form of disulfide linked polymers of incomplete mu chain. The molecular weight of the monomer was approximately 58,000. The protein comprised the Fc fragment and a part of the Fd segment. Bence Jones protein was not found in the urine."} {"id": "PMID:170663", "title": "[Relationship between avascular necrosis and lipid and purine metabolisms].", "content": "The serum levels of uric acid, triglycerides, cholesterol, and lipoproteins were determined in 35 patients suffering from primary avascular necrosis. The results were compared with those of a control group and with those of patients suffering from gout. The frequency distribution of the results in the three groups was of the log-normal type and statistical calculations were made on logarithmic transformations of the serum values. In comparison with the control group, significant increases in the levels of triglycerides, cholesterol, pre-beta-lipoproteins, and uric acid were observed in patients presenting an avascular necrosis. No significant differences were observed between these patients and patients with gout in the levels of lipids and lipoproteins. Uricaemia was higher in the gout patients. Contrary to observations made on the gout patients, there was no correlation in the avascular necrosis patients between the uric acid level and the serum levels of lipids or lipoproteins. In an earlier study the authors put forward an hypothesis according to which the close relationship between the lipid and purine metabolisms in gout patients was due to a genetic linkage based on a common enzyme defect, which directly affected the two metabolisms. In avascular necrosis there is no common enzyme defect; the initial event is a disturbance in the lipid metabolism. The authors conclude with data which tend to show that the bone necrosis observed in patients using steroids or alcohol is not directly induced by these substances, but that once again the initial event is a disturbance in the lipid metabolism.", "contents": "[Relationship between avascular necrosis and lipid and purine metabolisms]. The serum levels of uric acid, triglycerides, cholesterol, and lipoproteins were determined in 35 patients suffering from primary avascular necrosis. The results were compared with those of a control group and with those of patients suffering from gout. The frequency distribution of the results in the three groups was of the log-normal type and statistical calculations were made on logarithmic transformations of the serum values. In comparison with the control group, significant increases in the levels of triglycerides, cholesterol, pre-beta-lipoproteins, and uric acid were observed in patients presenting an avascular necrosis. No significant differences were observed between these patients and patients with gout in the levels of lipids and lipoproteins. Uricaemia was higher in the gout patients. Contrary to observations made on the gout patients, there was no correlation in the avascular necrosis patients between the uric acid level and the serum levels of lipids or lipoproteins. In an earlier study the authors put forward an hypothesis according to which the close relationship between the lipid and purine metabolisms in gout patients was due to a genetic linkage based on a common enzyme defect, which directly affected the two metabolisms. In avascular necrosis there is no common enzyme defect; the initial event is a disturbance in the lipid metabolism. The authors conclude with data which tend to show that the bone necrosis observed in patients using steroids or alcohol is not directly induced by these substances, but that once again the initial event is a disturbance in the lipid metabolism."} {"id": "PMID:170668", "title": "Antibiotic susceptibility of Clostridium species isolated from human infections.", "content": "In antibacterial susceptibility testing by the agar plate dilution method with 252 strains of Clostridium perfringens, 22 strains of C. novyi type A and 7 of C. novyi type B, with 21 strains of C. bifermentans, 12 strains of C. sordellii and 18 of C. sporogenes, the majority of the strains were inhibited by penicillin G, cephalothin, chloramphenicol, erythromycin, tinidazole and metronidazole. Resistance to lincomycin and clindamycin was noticed among strains of all clostridia species as well as to tetracycline and doxycycline among strains of C. perfringens.", "contents": "Antibiotic susceptibility of Clostridium species isolated from human infections. In antibacterial susceptibility testing by the agar plate dilution method with 252 strains of Clostridium perfringens, 22 strains of C. novyi type A and 7 of C. novyi type B, with 21 strains of C. bifermentans, 12 strains of C. sordellii and 18 of C. sporogenes, the majority of the strains were inhibited by penicillin G, cephalothin, chloramphenicol, erythromycin, tinidazole and metronidazole. Resistance to lincomycin and clindamycin was noticed among strains of all clostridia species as well as to tetracycline and doxycycline among strains of C. perfringens."} {"id": "PMID:170664", "title": "[Use of new osteotropic isotopes in osteoarticular diseases, with special reference to phlogistic arthropathies].", "content": "By using an osteotropic complex (99mTc pyrophosphate) scintigraphic and scintiphotographic images were obtained with a view to studying the bone changes in inflammatory arthropathies. In rheumatoid arthritis there is an increase in radioactivity next to affected joints and this phenomenon which seems to contrast with the osteoporosis of the juxta-articular regions is confirmed, since the reduced density that is observed in the radiograms is a result of the lack of equilibrium between bone formation and bone resorption, but only if these two processes are proceeding actively. The \"warm\" zones, which are very close to the joints, are just as easy to see in relation to inflamed joints as they are in relation to joints in which the inflammation has ceased. Not all the inflamed joints accumulate the radioactive osteotropic complex. The bone changes can occur in cases of chronic inflammatory arthropathies only if the inflammation has been present for at least several months. The images obtained with the polyphosphate correspond to those that can be obtained with other calcium-mimetic and osteotropic isotopes (Sr etc.).", "contents": "[Use of new osteotropic isotopes in osteoarticular diseases, with special reference to phlogistic arthropathies]. By using an osteotropic complex (99mTc pyrophosphate) scintigraphic and scintiphotographic images were obtained with a view to studying the bone changes in inflammatory arthropathies. In rheumatoid arthritis there is an increase in radioactivity next to affected joints and this phenomenon which seems to contrast with the osteoporosis of the juxta-articular regions is confirmed, since the reduced density that is observed in the radiograms is a result of the lack of equilibrium between bone formation and bone resorption, but only if these two processes are proceeding actively. The \"warm\" zones, which are very close to the joints, are just as easy to see in relation to inflamed joints as they are in relation to joints in which the inflammation has ceased. Not all the inflamed joints accumulate the radioactive osteotropic complex. The bone changes can occur in cases of chronic inflammatory arthropathies only if the inflammation has been present for at least several months. The images obtained with the polyphosphate correspond to those that can be obtained with other calcium-mimetic and osteotropic isotopes (Sr etc.)."} {"id": "PMID:170669", "title": "Regression line analysis for five antibiotics with strains of Clostridium species.", "content": "The susceptibility of 90 strains of clostridia to 5 antibacterials was determined by the agar plate dilution method and the disc diffusion test. The correlations between minimum inhibitory concentration and inhibition zone were quite acceptable for lincomycin, clindamycin, tetracycline and doxycycline to calculate regression lines by the least square method. The strains showed comparatively wide ranges of susceptibility. For erythromycin, no regression line could be calculated, since all the strains tested were susceptible over a narrow range of concentrations.", "contents": "Regression line analysis for five antibiotics with strains of Clostridium species. The susceptibility of 90 strains of clostridia to 5 antibacterials was determined by the agar plate dilution method and the disc diffusion test. The correlations between minimum inhibitory concentration and inhibition zone were quite acceptable for lincomycin, clindamycin, tetracycline and doxycycline to calculate regression lines by the least square method. The strains showed comparatively wide ranges of susceptibility. For erythromycin, no regression line could be calculated, since all the strains tested were susceptible over a narrow range of concentrations."} {"id": "PMID:170670", "title": "Cytarabine treatment of herpes simplex encephalitis in infants and small children. A report on three cases with a short review of the literature.", "content": "Three cytarabine-treated infants and children with herpes simplex encephalitis are presented. The effect of the treatment was excellent in 2 cases. One boy who had a CP syndrome died. It is assumed that the treatment with cytarabine should be started as early as possible with a dosage of 3 mg/kg body weight given intravenously once a day in a single injection for 5 days. No serious side effects have been noted. The advantage of cytarabine over idoxuridine, especially when treating small children and herpetic infections in the central nervous system, are emphasized.", "contents": "Cytarabine treatment of herpes simplex encephalitis in infants and small children. A report on three cases with a short review of the literature. Three cytarabine-treated infants and children with herpes simplex encephalitis are presented. The effect of the treatment was excellent in 2 cases. One boy who had a CP syndrome died. It is assumed that the treatment with cytarabine should be started as early as possible with a dosage of 3 mg/kg body weight given intravenously once a day in a single injection for 5 days. No serious side effects have been noted. The advantage of cytarabine over idoxuridine, especially when treating small children and herpetic infections in the central nervous system, are emphasized."} {"id": "PMID:170671", "title": "Survey of a neonatal population for the prevalence of cytomegalovirus.", "content": "A neonatal population of 542 was tested for cytomegaloviruria. 293 were normally grown and full term, 172 normally grown but premature, and 77 were undergrown. Two normally grown term infants and one premature were excreting the virus (o.55%). Only one, a normally grown term infant, had signs of classical cytomegalic inclusion disease. None of the undergrown infants was infected.", "contents": "Survey of a neonatal population for the prevalence of cytomegalovirus. A neonatal population of 542 was tested for cytomegaloviruria. 293 were normally grown and full term, 172 normally grown but premature, and 77 were undergrown. Two normally grown term infants and one premature were excreting the virus (o.55%). Only one, a normally grown term infant, had signs of classical cytomegalic inclusion disease. None of the undergrown infants was infected."} {"id": "PMID:170665", "title": "[A rare dental abnormality: \"the phantom tooth\" or \"odontodysplasia\". Apropos of a case].", "content": "\"Phantom tooth\" or \"odontodysplasia\" is one of the most unusual and rare of dental abnormalities, being characterised: Clinically, by the topography of the lesions, the involvement of both sets of teeth and abnormalities in the size and form of the teeth which remain unrupted or only partially evolved. Radiologically, by transparency of the teeth to X-rays. Histologically, by disorganisation of the dental structures and a highly characteristic appearance of the enamel and, in particular, dentine. On the basis of one case, the authors review in detail each aspect of these characteristics, paying special attention to histology and the information obtained using the sweep electron microscope.", "contents": "[A rare dental abnormality: \"the phantom tooth\" or \"odontodysplasia\". Apropos of a case]. \"Phantom tooth\" or \"odontodysplasia\" is one of the most unusual and rare of dental abnormalities, being characterised: Clinically, by the topography of the lesions, the involvement of both sets of teeth and abnormalities in the size and form of the teeth which remain unrupted or only partially evolved. Radiologically, by transparency of the teeth to X-rays. Histologically, by disorganisation of the dental structures and a highly characteristic appearance of the enamel and, in particular, dentine. On the basis of one case, the authors review in detail each aspect of these characteristics, paying special attention to histology and the information obtained using the sweep electron microscope."} {"id": "PMID:170672", "title": "Prolonged survival of non-multiplying Staphylococcus aureus cells undergoing autolysis in the presence of certain inhibitors of cell wall synthesis.", "content": "Certain antibiotic compounds including penicillin, cloxacillin and 6-APA caused a prolonged survival of Staph. aureus cells undergoing autolysis in physiologic saline. The retardation of the death rate was dependent upon the type of compound and its concentration. The results suggest that the compounds inhibit the autolytic function of the bacteria.", "contents": "Prolonged survival of non-multiplying Staphylococcus aureus cells undergoing autolysis in the presence of certain inhibitors of cell wall synthesis. Certain antibiotic compounds including penicillin, cloxacillin and 6-APA caused a prolonged survival of Staph. aureus cells undergoing autolysis in physiologic saline. The retardation of the death rate was dependent upon the type of compound and its concentration. The results suggest that the compounds inhibit the autolytic function of the bacteria."} {"id": "PMID:170673", "title": "Bronchial cancer - a clinical and pathological study. I. Histopathology and metastases.", "content": "Among 16,394 necropsies during the 12-year period, 1958-1969 (representing about 60% of all persons who died in Malm\u00f6 during this period, 747 cases of bronchial cancer were found in 744 individuals. There were considerable differences in frequency of different histologic types with regard to sex. Two main classes have therefore been distinguished: Group I, comprising squamous epithelial cancer and anaplastic cancer (including oat-cell cancer), which was predominant among men; and Group II, comprising adenocarcinoma, bronchiolar carcinoma, carcinoid and bronchial gland tumour, which was of more or less equal frequency in both sexes. Compared with other malignant tumours, bronchial carcinoma had a strong tendency to metastasise to the adrenals, brain, kidneys and skeleton. Bronchial cancer did not differ from other tumours with regard to lymphogenous spread but had a stronger tendency to spread via the blood stream. Squamous epithelial cancer showed the strongest tendency to remain confined to the thoracic cavity.", "contents": "Bronchial cancer - a clinical and pathological study. I. Histopathology and metastases. Among 16,394 necropsies during the 12-year period, 1958-1969 (representing about 60% of all persons who died in Malm\u00f6 during this period, 747 cases of bronchial cancer were found in 744 individuals. There were considerable differences in frequency of different histologic types with regard to sex. Two main classes have therefore been distinguished: Group I, comprising squamous epithelial cancer and anaplastic cancer (including oat-cell cancer), which was predominant among men; and Group II, comprising adenocarcinoma, bronchiolar carcinoma, carcinoid and bronchial gland tumour, which was of more or less equal frequency in both sexes. Compared with other malignant tumours, bronchial carcinoma had a strong tendency to metastasise to the adrenals, brain, kidneys and skeleton. Bronchial cancer did not differ from other tumours with regard to lymphogenous spread but had a stronger tendency to spread via the blood stream. Squamous epithelial cancer showed the strongest tendency to remain confined to the thoracic cavity."} {"id": "PMID:170674", "title": "Bronchial cancer - a clinical and pathological study. II. Frequency according to age and sex during a 12-year period.", "content": "A necropsy series of bronchial cancer combined with a retrospective clinical study comprising 747 cases of bronchial cancer from a defined population is described. A significant successive increase in the frequency of bronchial cancer during the 12-year period 1958-1969 was found. The increase during three successive 3-year periods will be as much as 45, 86 and 146%, respectively, if the 1958-1960 frequency is set to 100%. In contrast to many other investigations this increase was found in both women and men (the relative increase was exactly the same in both sexes) and for both Group I and Group II tumours. The ratios between men and women and between Group I and Group II tumours in the present material were thus constant throughout the investigation. This may be explained by the assumption that the female population today has smoked cigarettes for a sufficiently long period to stimulate the development of bronchial cancer and that there seems also to be a correlation between Group II tumours and cigarette smoking.", "contents": "Bronchial cancer - a clinical and pathological study. II. Frequency according to age and sex during a 12-year period. A necropsy series of bronchial cancer combined with a retrospective clinical study comprising 747 cases of bronchial cancer from a defined population is described. A significant successive increase in the frequency of bronchial cancer during the 12-year period 1958-1969 was found. The increase during three successive 3-year periods will be as much as 45, 86 and 146%, respectively, if the 1958-1960 frequency is set to 100%. In contrast to many other investigations this increase was found in both women and men (the relative increase was exactly the same in both sexes) and for both Group I and Group II tumours. The ratios between men and women and between Group I and Group II tumours in the present material were thus constant throughout the investigation. This may be explained by the assumption that the female population today has smoked cigarettes for a sufficiently long period to stimulate the development of bronchial cancer and that there seems also to be a correlation between Group II tumours and cigarette smoking."} {"id": "PMID:170675", "title": "[Hypolipidemias].", "content": "Hypolipidemias can be divided in primary, familial and hereditary forms and symptomatic forms which may accompany other diseases. The primary hypolipidemias (abetalipoproteinemia, hypobetalipoproteinemia and analphalipoproteinemia) are very rare. Severe hypolipidemia can be found in some peoples (e.g. the Masai). This article is chiefly devoted to secondary hypolipidemias such as those associated with malabsorption, malnutrition and maldigestion including protein-losing gastroenteropathy, with liver diseases, endocrine diseases (hyperthyroidism, hirsutism) and anemia. Finally, the hypolipidemias secondary to the formation of autoantibodies against HDL and LDL in M-gradient, carcinoma and rheumatoid arthritis are briefly reviewed.", "contents": "[Hypolipidemias]. Hypolipidemias can be divided in primary, familial and hereditary forms and symptomatic forms which may accompany other diseases. The primary hypolipidemias (abetalipoproteinemia, hypobetalipoproteinemia and analphalipoproteinemia) are very rare. Severe hypolipidemia can be found in some peoples (e.g. the Masai). This article is chiefly devoted to secondary hypolipidemias such as those associated with malabsorption, malnutrition and maldigestion including protein-losing gastroenteropathy, with liver diseases, endocrine diseases (hyperthyroidism, hirsutism) and anemia. Finally, the hypolipidemias secondary to the formation of autoantibodies against HDL and LDL in M-gradient, carcinoma and rheumatoid arthritis are briefly reviewed."} {"id": "PMID:170676", "title": "Enhancement of mouse cytomegalovirus infection during host-versus-graft reaction.", "content": "C3H/He mice chronically infected with murine cytomegalovirus were given skin allografts from histoincompatible BALB/c donors. A significant increase in cytomegalovirus titers occurred within 3 days after placement of the graft in the spleens and kidneys of the allograft recipients as compared with control animals. No significant changes in virus titers were detected in the salivary gland, lung, liver, or blood of allograft recipients. These results indicate that the host-versus-graft reaction alone can enhance murine cytomegalovirus in a chronically infected host and may help explain the high incidence of cytomegalovirus infection seen after renal and other allograft transplantation in man.", "contents": "Enhancement of mouse cytomegalovirus infection during host-versus-graft reaction. C3H/He mice chronically infected with murine cytomegalovirus were given skin allografts from histoincompatible BALB/c donors. A significant increase in cytomegalovirus titers occurred within 3 days after placement of the graft in the spleens and kidneys of the allograft recipients as compared with control animals. No significant changes in virus titers were detected in the salivary gland, lung, liver, or blood of allograft recipients. These results indicate that the host-versus-graft reaction alone can enhance murine cytomegalovirus in a chronically infected host and may help explain the high incidence of cytomegalovirus infection seen after renal and other allograft transplantation in man."} {"id": "PMID:170677", "title": "Increased urinary excretion of cyclic guanosine monophosphate in rats bearing Morris hepatoma 3924A.", "content": "Urinary excretion of cyclic guanosine monophosphate (GMP) increased in rats bearing Morris hepatoma 3924A, and a correlation coefficient of .842 was observed comparing nucleotide excretion and tumor size. Irradiation of tumor or 5-fluorouracil administration delayed the increases in urinary cyclic GMP and tumor size. Surgical removal of tumors resulted in a rapid decline in cyclic GMP excretion to baseline levels. Cyclic adenosine monophosphate excretion was not altered by implantation, irradiation, or excision of tumor.", "contents": "Increased urinary excretion of cyclic guanosine monophosphate in rats bearing Morris hepatoma 3924A. Urinary excretion of cyclic guanosine monophosphate (GMP) increased in rats bearing Morris hepatoma 3924A, and a correlation coefficient of .842 was observed comparing nucleotide excretion and tumor size. Irradiation of tumor or 5-fluorouracil administration delayed the increases in urinary cyclic GMP and tumor size. Surgical removal of tumors resulted in a rapid decline in cyclic GMP excretion to baseline levels. Cyclic adenosine monophosphate excretion was not altered by implantation, irradiation, or excision of tumor."} {"id": "PMID:170678", "title": "Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance.", "content": "Six patients with a unique form of diabetes associated with extreme insulin resistance have markedly reduced insulin binding to specific receptors on their circulating monocytes. When normal insulin receptors were exposed to serum or immunoglobulin fractions from three of these patients in vitro the specific binding defect was reproduced.", "contents": "Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance. Six patients with a unique form of diabetes associated with extreme insulin resistance have markedly reduced insulin binding to specific receptors on their circulating monocytes. When normal insulin receptors were exposed to serum or immunoglobulin fractions from three of these patients in vitro the specific binding defect was reproduced."} {"id": "PMID:170679", "title": "Magnetotactic bacteria.", "content": "Bacteria with motility directed by the local geomagnetic field have been observed in marine sediments. These magnetotactic microorganisms possess flagella and contain novel structured particles, rich in iron, within intracytoplasmic membrane vesicles. Conceivably these particles impart to cells a magnetic moment. This could explain the observed migration of these organisms in fields as weak as 0.5 gauss.", "contents": "Magnetotactic bacteria. Bacteria with motility directed by the local geomagnetic field have been observed in marine sediments. These magnetotactic microorganisms possess flagella and contain novel structured particles, rich in iron, within intracytoplasmic membrane vesicles. Conceivably these particles impart to cells a magnetic moment. This could explain the observed migration of these organisms in fields as weak as 0.5 gauss."} {"id": "PMID:170680", "title": "Heteropolypeptides from poly-alpha-cyanoglycine and hydrogen cyanide: a model for the origin of proteins.", "content": "Poly-alpha-cyanoglycine, a homopolymer synthesized from the N-carboxyanhydride of alpha-cyanoglycine, is converted by cumulative reaction of hydrogen cyanide to heteropolypeptides that can be hydrolyzed to protein amino acids, including glycine, alanine, valine, aspartic acid, and glutamic acid. These results are consistent with the hypothesis that the original heteropolypeptides on the earth arose spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids.", "contents": "Heteropolypeptides from poly-alpha-cyanoglycine and hydrogen cyanide: a model for the origin of proteins. Poly-alpha-cyanoglycine, a homopolymer synthesized from the N-carboxyanhydride of alpha-cyanoglycine, is converted by cumulative reaction of hydrogen cyanide to heteropolypeptides that can be hydrolyzed to protein amino acids, including glycine, alanine, valine, aspartic acid, and glutamic acid. These results are consistent with the hypothesis that the original heteropolypeptides on the earth arose spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids."} {"id": "PMID:170681", "title": "Thermal transitions in human plasma low density lipoproteins.", "content": "Thermal analysis of human plasma low density lipoproteins reveals a broad reversible transition encompassing body temperature. The calorimetric and x-ray scattering data identify this transition as a cooperation, liquid-crystalline to liquid phase change involving the cholesterol esters in the lipoprotein. This behavior requires the presence of a region rich in cholesterol ester within the lipoprotein.", "contents": "Thermal transitions in human plasma low density lipoproteins. Thermal analysis of human plasma low density lipoproteins reveals a broad reversible transition encompassing body temperature. The calorimetric and x-ray scattering data identify this transition as a cooperation, liquid-crystalline to liquid phase change involving the cholesterol esters in the lipoprotein. This behavior requires the presence of a region rich in cholesterol ester within the lipoprotein."} {"id": "PMID:170682", "title": "Electron microscopy of albumin synthesis.", "content": "Albumin molecules appeared to be synthesized in the light hepatocytes of rats by bound polysomers on rough and endoplasmic reticulum and the nuclear envelope. The molecules were discharged directly into the cytosol, then to the external cellular spaces. This conclusion failed to support the current theory from biochemical studies that albumin is synthesized by bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, and transported to the smooth endoplasmic reticulum and then to the Golgi apparatus. In addition to the liver, positive syntheic activities were observed in the aorta, kidney, and hepatoma cells of rat. Earlier investigators have reported that only liver cells can synthesize albumin.", "contents": "Electron microscopy of albumin synthesis. Albumin molecules appeared to be synthesized in the light hepatocytes of rats by bound polysomers on rough and endoplasmic reticulum and the nuclear envelope. The molecules were discharged directly into the cytosol, then to the external cellular spaces. This conclusion failed to support the current theory from biochemical studies that albumin is synthesized by bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, and transported to the smooth endoplasmic reticulum and then to the Golgi apparatus. In addition to the liver, positive syntheic activities were observed in the aorta, kidney, and hepatoma cells of rat. Earlier investigators have reported that only liver cells can synthesize albumin."} {"id": "PMID:170683", "title": "Visually evoked magnetic fields of the human brain.", "content": "Magnetic field variations from the human brain produced by visual stimulation have been observed in a normal laboratory setting with a superconducting quantum interference device and no magnetic shielding of the subject. Previously unknown temporal and spatial features of the field near the scalp are reported.", "contents": "Visually evoked magnetic fields of the human brain. Magnetic field variations from the human brain produced by visual stimulation have been observed in a normal laboratory setting with a superconducting quantum interference device and no magnetic shielding of the subject. Previously unknown temporal and spatial features of the field near the scalp are reported."} {"id": "PMID:170688", "title": "Malignant fibrous histiocytoma.", "content": "Two patients are presented who had malignant fibrous histiocytomas of the skin and soft tissue. These tumors characteristically consist of a solitary mass, 0.5 cm to 12.0 cm, which has skin fixation, is circumscribed and firm. Microscopically, there is a pattern of histiocytes and bizarre histiocytic giant cells intermingled in a fibrous stroma with fibroblasts arranged in a whirling pattern. The lesion is treated with wide excision and skin grafting. Local recurrence is common. Metastasis is less common, but with metastasis the prognosis is poor.", "contents": "Malignant fibrous histiocytoma. Two patients are presented who had malignant fibrous histiocytomas of the skin and soft tissue. These tumors characteristically consist of a solitary mass, 0.5 cm to 12.0 cm, which has skin fixation, is circumscribed and firm. Microscopically, there is a pattern of histiocytes and bizarre histiocytic giant cells intermingled in a fibrous stroma with fibroblasts arranged in a whirling pattern. The lesion is treated with wide excision and skin grafting. Local recurrence is common. Metastasis is less common, but with metastasis the prognosis is poor."} {"id": "PMID:170690", "title": "Arbovirus infections in reptiles: studies on the presence of Japanese encephalitis virus antibody in the plasma of the turtle, Trionyx sinensis.", "content": "This study was undertaken to examine further the natural infection of poikilothermic animals e.g. turtles, to Japanese encephalitis (JE) virus. Plasma samples from 75 soft-shelled fresh water turtles (Trionyx sinensis Wiegman) from China were examined in virus neutralization (VN) and hemagglutination inhibition (HAI) tests for the presence of specific antibody. The total incidence of antibody detected by either test to a titer of 10 or greater was 89% while 77% and 60% were positive by VN and HAI tests, respectively. Forty-one per cent were jointly positive by both tests. Mean HAI and VN titers were similar and showed no obvious differences between spring/summer and autumn/winter seasons. The HAI reactivity was associated with a 7S component for both seasons. The significance of this inhibition in the serology of poikilothermic hosts and the possible behaviour of T. sinensis in the natural history of JE virus is briefly considered.", "contents": "Arbovirus infections in reptiles: studies on the presence of Japanese encephalitis virus antibody in the plasma of the turtle, Trionyx sinensis. This study was undertaken to examine further the natural infection of poikilothermic animals e.g. turtles, to Japanese encephalitis (JE) virus. Plasma samples from 75 soft-shelled fresh water turtles (Trionyx sinensis Wiegman) from China were examined in virus neutralization (VN) and hemagglutination inhibition (HAI) tests for the presence of specific antibody. The total incidence of antibody detected by either test to a titer of 10 or greater was 89% while 77% and 60% were positive by VN and HAI tests, respectively. Forty-one per cent were jointly positive by both tests. Mean HAI and VN titers were similar and showed no obvious differences between spring/summer and autumn/winter seasons. The HAI reactivity was associated with a 7S component for both seasons. The significance of this inhibition in the serology of poikilothermic hosts and the possible behaviour of T. sinensis in the natural history of JE virus is briefly considered."} {"id": "PMID:170684", "title": "[Spontaneous pneumomediastinum].", "content": "Spontaneous pneumomediastinum is a relatively rare disease, the clinical signs of which may be misleading, and the physiopathology is still unknown. The authors report 7 cases collected over a period of 3 years and note the etiology, the clinical findings and the X-ray findings. The disease often affectsyoung sybjects, without any sex predominance. The initial symptom is thoracic pain and is often accompanied by dispnea. Subcutaneous emphysema only appears secondarily and may be mild. The association with pneumothorax is not rare. Among the etiological circumstances, pneumomediastinum often occurs after an effort or a respiratory infection with dyspnea. The diagnosis depends on the discovery of subcutaneous emphysema and on radiological signs in A.P. and lateral chest views. Treatment should be as conservative as possible in the usual benign forms. It should be limited to bed rest, analgesics and sedatives. In severe cases, supra-sternal drainage permits decompression of the mediastinum. The physiopathological mechanisms are discussed, but the usually accepted theory is rupture of an alveolus into the pulmonary interstitial tissue. The pressure gradient necessary for this rupture may be due to variations in alveolar or vascular pressure.", "contents": "[Spontaneous pneumomediastinum]. Spontaneous pneumomediastinum is a relatively rare disease, the clinical signs of which may be misleading, and the physiopathology is still unknown. The authors report 7 cases collected over a period of 3 years and note the etiology, the clinical findings and the X-ray findings. The disease often affectsyoung sybjects, without any sex predominance. The initial symptom is thoracic pain and is often accompanied by dispnea. Subcutaneous emphysema only appears secondarily and may be mild. The association with pneumothorax is not rare. Among the etiological circumstances, pneumomediastinum often occurs after an effort or a respiratory infection with dyspnea. The diagnosis depends on the discovery of subcutaneous emphysema and on radiological signs in A.P. and lateral chest views. Treatment should be as conservative as possible in the usual benign forms. It should be limited to bed rest, analgesics and sedatives. In severe cases, supra-sternal drainage permits decompression of the mediastinum. The physiopathological mechanisms are discussed, but the usually accepted theory is rupture of an alveolus into the pulmonary interstitial tissue. The pressure gradient necessary for this rupture may be due to variations in alveolar or vascular pressure."} {"id": "PMID:170685", "title": "[Information obtained by liver biopsy in 100 tuberculous patients].", "content": "The results of liver biopsy in 100 patients with tuberculosis are reported. In 8 patients, biopsy only occurred secondarily, during liver disease which appeared during antituberculous treatment. In five cases, the association of rifamycin and isoniazid was probably responsible and the mild histological signs noted suggested a favourable course after stopping one of the drugs or simply reducing the dose. The 3 other patients had virus hepatitis and biopsy was of prognostic interest by revealing the onset of post-hepatic cirrhosis. In 92 cases, liver biopsy was carried out before treatment. In 34 cases the liver was normal, in 38 patients there were hisotlogical changes which did not suggest tuberculosis but, probably, alcoholism. These were : steatosis, in 21 cases, cirrhosis in 8 cases, a mixture of steatosis and cirrhosis in 4 cases, and acute alcoholic hepatitis in 5 cases. Finally, in 20 cases, biopsy revealed an appearance of granulomatous hepatitis. Although this lesion is significant in the development of the disease, it is not characteristic of tuberculosis unless there is caseous necrosis, as in 2 cases, and unless culture of the biopsy material is positive, as in one case out of 9, i.e. the diagnostic interest of liver biopsy is not very great compared with prognostic interest. By determining the anatomical condition of the liver, often not obvious when simple liver function tests are carried out, it permits one to forsee to some extent the tolerance of the liver to antituberculous treatment, especially in alcoholics.", "contents": "[Information obtained by liver biopsy in 100 tuberculous patients]. The results of liver biopsy in 100 patients with tuberculosis are reported. In 8 patients, biopsy only occurred secondarily, during liver disease which appeared during antituberculous treatment. In five cases, the association of rifamycin and isoniazid was probably responsible and the mild histological signs noted suggested a favourable course after stopping one of the drugs or simply reducing the dose. The 3 other patients had virus hepatitis and biopsy was of prognostic interest by revealing the onset of post-hepatic cirrhosis. In 92 cases, liver biopsy was carried out before treatment. In 34 cases the liver was normal, in 38 patients there were hisotlogical changes which did not suggest tuberculosis but, probably, alcoholism. These were : steatosis, in 21 cases, cirrhosis in 8 cases, a mixture of steatosis and cirrhosis in 4 cases, and acute alcoholic hepatitis in 5 cases. Finally, in 20 cases, biopsy revealed an appearance of granulomatous hepatitis. Although this lesion is significant in the development of the disease, it is not characteristic of tuberculosis unless there is caseous necrosis, as in 2 cases, and unless culture of the biopsy material is positive, as in one case out of 9, i.e. the diagnostic interest of liver biopsy is not very great compared with prognostic interest. By determining the anatomical condition of the liver, often not obvious when simple liver function tests are carried out, it permits one to forsee to some extent the tolerance of the liver to antituberculous treatment, especially in alcoholics."} {"id": "PMID:170686", "title": "[Achillean reflexogram : its measurement and its correlations with various clinical and biological factors in 2 working male populations].", "content": "The achillean reflexogram has been recorded according to Gilson's photo-electric technique among two male populations during routine cardio-vascular screening. The first population concerns 706 men aged 21 to 55 and the second one 4 437 subjects aged 46 to 52. The frequency of bilateral areflexy increases with age (from 3% before 30 to 6% after 40); it is significantly associated with the presence of angina pectoris. However, no relation is observed with diabetes or clinical suspicion of myocardial infarction. Whereas fat body mass is positively associated with the reflex duration the latter is reduced with heart rate, systolic blooc pressure and number of blood erythrocytes and leucocytes increased. These results and the interest of systematic reflexogram recording during health check up are discussed.", "contents": "[Achillean reflexogram : its measurement and its correlations with various clinical and biological factors in 2 working male populations]. The achillean reflexogram has been recorded according to Gilson's photo-electric technique among two male populations during routine cardio-vascular screening. The first population concerns 706 men aged 21 to 55 and the second one 4 437 subjects aged 46 to 52. The frequency of bilateral areflexy increases with age (from 3% before 30 to 6% after 40); it is significantly associated with the presence of angina pectoris. However, no relation is observed with diabetes or clinical suspicion of myocardial infarction. Whereas fat body mass is positively associated with the reflex duration the latter is reduced with heart rate, systolic blooc pressure and number of blood erythrocytes and leucocytes increased. These results and the interest of systematic reflexogram recording during health check up are discussed."} {"id": "PMID:170694", "title": "Intracellular enzyme liberation in primate spinal cord injury.", "content": "Intracellular lysosomal and nonlysosomal enzymes, as well as tissue edema, were measured in spinal cords of monkeys up to 20 days following a 300 gm-cm open injury. Although edema was maximal between six hours and 11 days, enzyme elevation was delayed. Lysosomal enzyme acid cathepsin increased beginning at five days and the beta-glucuronidase and beta-glycerophosphatase increase began at 11 days. Nonlysosomal enzymes were either not elevated or showed a slight rise. These data suggest that edema, one of the secondary damaging factors in spinal injury, is not a result of release of these intracellular enzymes. Also it appears that intracellular enzymes do not participate in early secondary damaging processes in severe spinal injury.", "contents": "Intracellular enzyme liberation in primate spinal cord injury. Intracellular lysosomal and nonlysosomal enzymes, as well as tissue edema, were measured in spinal cords of monkeys up to 20 days following a 300 gm-cm open injury. Although edema was maximal between six hours and 11 days, enzyme elevation was delayed. Lysosomal enzyme acid cathepsin increased beginning at five days and the beta-glucuronidase and beta-glycerophosphatase increase began at 11 days. Nonlysosomal enzymes were either not elevated or showed a slight rise. These data suggest that edema, one of the secondary damaging factors in spinal injury, is not a result of release of these intracellular enzymes. Also it appears that intracellular enzymes do not participate in early secondary damaging processes in severe spinal injury."} {"id": "PMID:170695", "title": "Organization of peripheral and central pain pathways.", "content": "The organizational features of the somatosensory system that may be significant to the perception of noxious stimuli are reviewed, with emphasis on the integration that likely occurs among both ascending and descending pathways.", "contents": "Organization of peripheral and central pain pathways. The organizational features of the somatosensory system that may be significant to the perception of noxious stimuli are reviewed, with emphasis on the integration that likely occurs among both ascending and descending pathways."} {"id": "PMID:170696", "title": "Clinical experience with the intravenous infusion of iodinated contrast material as an adjunct to computed tomography.", "content": "The intravenous infusion of iodinated contrast material is an important adjunct to computed tomography with a wide variety of lesions. Some arteriovenous malformations, metastatic lesions and tumors of the sella turcica and cerebellopontine angle which are undetectable by conventional computed tomography may be visualized by this method. Certain other metastatic lesions, primary tumors, abscesses and infarcts which are detectable in the preinfusion tomogram become better defined following infusion. The indications for this examination and the procedures involved are discussed.", "contents": "Clinical experience with the intravenous infusion of iodinated contrast material as an adjunct to computed tomography. The intravenous infusion of iodinated contrast material is an important adjunct to computed tomography with a wide variety of lesions. Some arteriovenous malformations, metastatic lesions and tumors of the sella turcica and cerebellopontine angle which are undetectable by conventional computed tomography may be visualized by this method. Certain other metastatic lesions, primary tumors, abscesses and infarcts which are detectable in the preinfusion tomogram become better defined following infusion. The indications for this examination and the procedures involved are discussed."} {"id": "PMID:170697", "title": "Biological behavior of the primitive neuroectodermal tumors: significant supratentorial childhood gliomas.", "content": "Supratentorial gliomas in the pediatric age group at the University of Kentucky Medical Center accounted for 20% of all childhood brain tumors. Seventeen of the 20 children with these tumors, regardless of histologic type, mode of therapy, or other parameters died within five years after tissue diagnosis, and most were dead within two years. Unlike the astrocytic gliomas, the poorly differentiated primitive neuroectodermal tumors tended to spread diffusely throughout the central nervous system and accounted for 35% of the supratentorial gliomas in children at our institution. Results of this study suggest that therapy for the primitive neuroectodermal tumor, unlike other childhood supratentorial gliomas, should be considered for the entire neuraxis.", "contents": "Biological behavior of the primitive neuroectodermal tumors: significant supratentorial childhood gliomas. Supratentorial gliomas in the pediatric age group at the University of Kentucky Medical Center accounted for 20% of all childhood brain tumors. Seventeen of the 20 children with these tumors, regardless of histologic type, mode of therapy, or other parameters died within five years after tissue diagnosis, and most were dead within two years. Unlike the astrocytic gliomas, the poorly differentiated primitive neuroectodermal tumors tended to spread diffusely throughout the central nervous system and accounted for 35% of the supratentorial gliomas in children at our institution. Results of this study suggest that therapy for the primitive neuroectodermal tumor, unlike other childhood supratentorial gliomas, should be considered for the entire neuraxis."} {"id": "PMID:170698", "title": "Effect of total hepatectomy on selected cerebral substrates and enzymes of the glycolytic pathways and Krebs cycle.", "content": "Posthepatectomy coma was produced in 13 dogs and the cerebrums were biopsied for analysis of concentrations of glucose, glucose-6-phosphate, dihydroxyacetone-phosphate, phosphoenolpyruvate, pyruvate, lactate, citrate, alpha-ketogulutarate, fumarate, malate, oxaloacetate, adenosinetriphosphate, ammonia, and glutamine as well as for activities of glucokinase, phosphofructokinase, pyruvate kinase, isocitrate dehydrogenase, glutamate dehydrogenase, malate dehydrogenase, and malic enzyme. There were no differences from normal in the brain glycolytic substrate concentrations. Four of the Krebs cycle substrates were significantly reduced, but not differently than in dogs sedated for 24 hours. The glycolytic pathway, Krebs cycle, and related enzyme activities were not significantly altered. Cerebral adenosine triphosphate concentration was unchanged but the concentrations of ammonia and glutamine increased threefold.", "contents": "Effect of total hepatectomy on selected cerebral substrates and enzymes of the glycolytic pathways and Krebs cycle. Posthepatectomy coma was produced in 13 dogs and the cerebrums were biopsied for analysis of concentrations of glucose, glucose-6-phosphate, dihydroxyacetone-phosphate, phosphoenolpyruvate, pyruvate, lactate, citrate, alpha-ketogulutarate, fumarate, malate, oxaloacetate, adenosinetriphosphate, ammonia, and glutamine as well as for activities of glucokinase, phosphofructokinase, pyruvate kinase, isocitrate dehydrogenase, glutamate dehydrogenase, malate dehydrogenase, and malic enzyme. There were no differences from normal in the brain glycolytic substrate concentrations. Four of the Krebs cycle substrates were significantly reduced, but not differently than in dogs sedated for 24 hours. The glycolytic pathway, Krebs cycle, and related enzyme activities were not significantly altered. Cerebral adenosine triphosphate concentration was unchanged but the concentrations of ammonia and glutamine increased threefold."} {"id": "PMID:170700", "title": "Bronchodilator drug efficacy via cyclic AMP.", "content": "Cyclic adenosine 3', 5'-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system.", "contents": "Bronchodilator drug efficacy via cyclic AMP. Cyclic adenosine 3', 5'-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system."} {"id": "PMID:170701", "title": "A review of routine tests for respiratory viruses in hospital inpatients.", "content": "During the period June 1967 to May 1972, viral tests were performed upon 1195 inpatients aged 12 and over in the Brompton Hospital. The overall diagnostic rate was 21-5%, comparing 9-3% by isolation and 14-9% by complement fixation (6-5% by four-fold rises in titre in paired sera, 8-4% by titres larger than or equal to 160 in single sera). Only 42% of all patients had an acute respiratory illness within one week prior to admission, which seriously curtailed the chances of isolating viruses and of obtaining early serological specimens. The value of complement fixation tests on single specimens in the clinical management of patients is discussed. The profound effect of infections by influenza A on respiratory morbidity and hospital admission is stressed.", "contents": "A review of routine tests for respiratory viruses in hospital inpatients. During the period June 1967 to May 1972, viral tests were performed upon 1195 inpatients aged 12 and over in the Brompton Hospital. The overall diagnostic rate was 21-5%, comparing 9-3% by isolation and 14-9% by complement fixation (6-5% by four-fold rises in titre in paired sera, 8-4% by titres larger than or equal to 160 in single sera). Only 42% of all patients had an acute respiratory illness within one week prior to admission, which seriously curtailed the chances of isolating viruses and of obtaining early serological specimens. The value of complement fixation tests on single specimens in the clinical management of patients is discussed. The profound effect of infections by influenza A on respiratory morbidity and hospital admission is stressed."} {"id": "PMID:170702", "title": "Autoantibodies in patients with bronchial carcinoma.", "content": "No overall increase in the incidence of antinuclear, smooth muscle or reticulin antibodies was observed in a group of 105 patients with bronchial carcinoma of various classified histological types. Smooth muscle antibody was, however, demonstrated in 27% of patients with undifferentiated carcinoma compared to 5% of controls (P less than 0-05). A highly significant increase in antinuclear antibodies in patients with adenocarcinoma was found (31% compared with 5% of controls--P less than 0-01). There as no apparent correlation between the presence of these antibodies and age, sex or other clinical features studied. A detailed study of the reproducibility of the antibody results, studied by indirect immunofluorescence in patients with bronchial carcinoma, is reported.", "contents": "Autoantibodies in patients with bronchial carcinoma. No overall increase in the incidence of antinuclear, smooth muscle or reticulin antibodies was observed in a group of 105 patients with bronchial carcinoma of various classified histological types. Smooth muscle antibody was, however, demonstrated in 27% of patients with undifferentiated carcinoma compared to 5% of controls (P less than 0-05). A highly significant increase in antinuclear antibodies in patients with adenocarcinoma was found (31% compared with 5% of controls--P less than 0-01). There as no apparent correlation between the presence of these antibodies and age, sex or other clinical features studied. A detailed study of the reproducibility of the antibody results, studied by indirect immunofluorescence in patients with bronchial carcinoma, is reported."} {"id": "PMID:170703", "title": "Tetracosactrin for the management of asthmatic patients after long-term corticosteroids.", "content": "Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression.", "contents": "Tetracosactrin for the management of asthmatic patients after long-term corticosteroids. Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression."} {"id": "PMID:170707", "title": "The HL-A and ABO antigens in trophoblastic disease.", "content": "No statistically significant deviations in phenotype frequencies of the 25 HL-A antigens or the ABO antigens were seen when 111 Caucasian patients with trophoblastic disease were compared with 1,259 healthy Caucasian controls. However, an increasein the incidence of HL-A11 was found in 39 patients who currently had the disease, but not in 72 who had recovered from the disease. Further, an increase in the frequency of W18 was observed among 18 patients who currently had 'invasive' disease (choriocarcinoma or invasive mole), but not in 44 who had recovered from such disease. If valid for larger patient population, these increases may suggest association of HL-A11 and W18 with the 'morbidity' of the trophoblastic disease. No increase in histocompatibility was seen in 45 patient-couples over 67 control-couples in terms of decrease in the number of male spouse's HL-A incompatibilities, and no significant difference was seen in the distribution of pregnancies in the two groups. No significant difference was observed in the incidence of different male-female combinations of ABO blood groups between 95 patient-couples and an equal number of control-couples. Lymphocytotoxic antibodies were found in 64 patients (158 sera) or 36% of the 178 patients (413 sera) examined. HL-A specific antibodies were found in 30 or 17% patients (39 sera). Of these 30, 24 patients had molar pregnancies and six had choriocarcinoma. Whether these antibodies have a role in the destruction of neoplastic tissue remains to be determined.", "contents": "The HL-A and ABO antigens in trophoblastic disease. No statistically significant deviations in phenotype frequencies of the 25 HL-A antigens or the ABO antigens were seen when 111 Caucasian patients with trophoblastic disease were compared with 1,259 healthy Caucasian controls. However, an increasein the incidence of HL-A11 was found in 39 patients who currently had the disease, but not in 72 who had recovered from the disease. Further, an increase in the frequency of W18 was observed among 18 patients who currently had 'invasive' disease (choriocarcinoma or invasive mole), but not in 44 who had recovered from such disease. If valid for larger patient population, these increases may suggest association of HL-A11 and W18 with the 'morbidity' of the trophoblastic disease. No increase in histocompatibility was seen in 45 patient-couples over 67 control-couples in terms of decrease in the number of male spouse's HL-A incompatibilities, and no significant difference was seen in the distribution of pregnancies in the two groups. No significant difference was observed in the incidence of different male-female combinations of ABO blood groups between 95 patient-couples and an equal number of control-couples. Lymphocytotoxic antibodies were found in 64 patients (158 sera) or 36% of the 178 patients (413 sera) examined. HL-A specific antibodies were found in 30 or 17% patients (39 sera). Of these 30, 24 patients had molar pregnancies and six had choriocarcinoma. Whether these antibodies have a role in the destruction of neoplastic tissue remains to be determined."} {"id": "PMID:170708", "title": "Fine structure of the compound eye of Porcellio scaber in light and dark adaption.", "content": "The compound eyes of the terrestrial isopod Porcellio scaber comprises about 20 ommatidia. The dioptric apparatus of each ommatidia includes a biconvex corneal lens and a spherical crystalline cone that is secreted by two cone cells. The closed rhabdom is formed by the microvillar extensions of seven pigmented retinula cells and one apical eccentric cell. All retinular axons exit the eye in one bundle. During dark-adaption pigment granules in the retinula cells rapidly withdrew from around the rhabdom and the cell periphery, and migrated basally. Rhabdoms thickened because of movement of the microvilli, and mitochondria moved medially and basally. During light adaption these processes were reversed. Multivesicular bodies became less numerous and rough endoplasmic reticulum and ribosomes proliferated during the initial stages of light adaption.", "contents": "Fine structure of the compound eye of Porcellio scaber in light and dark adaption. The compound eyes of the terrestrial isopod Porcellio scaber comprises about 20 ommatidia. The dioptric apparatus of each ommatidia includes a biconvex corneal lens and a spherical crystalline cone that is secreted by two cone cells. The closed rhabdom is formed by the microvillar extensions of seven pigmented retinula cells and one apical eccentric cell. All retinular axons exit the eye in one bundle. During dark-adaption pigment granules in the retinula cells rapidly withdrew from around the rhabdom and the cell periphery, and migrated basally. Rhabdoms thickened because of movement of the microvilli, and mitochondria moved medially and basally. During light adaption these processes were reversed. Multivesicular bodies became less numerous and rough endoplasmic reticulum and ribosomes proliferated during the initial stages of light adaption."} {"id": "PMID:170709", "title": "Secretory end-feet, extracerebral cells, and cerebral sense organs in certain limicole oligochaete annelids.", "content": "Secretory end-feet (or SEF) systems are present in Limnodrilus and Stylodrilus but are less highly organized than those of polychaetes. SEF contain secretory vesicles and abundant mitochondria. Typical neurosecretory terminals are not found within the brain although \"neurosecretory\" perikarya are present in all four species studied. In Limnodrilus, Stylodrilus and Enchytraeus extracerebral cells, of probable neurosecretory function, are invested by the pericapsular epithelium. Characteristically such cells bear several cilia. In these species and in Stylaria a pair of sensory cell groups is located anteriorly within the brain. These cells are ciliated but lack associated supporting cells.", "contents": "Secretory end-feet, extracerebral cells, and cerebral sense organs in certain limicole oligochaete annelids. Secretory end-feet (or SEF) systems are present in Limnodrilus and Stylodrilus but are less highly organized than those of polychaetes. SEF contain secretory vesicles and abundant mitochondria. Typical neurosecretory terminals are not found within the brain although \"neurosecretory\" perikarya are present in all four species studied. In Limnodrilus, Stylodrilus and Enchytraeus extracerebral cells, of probable neurosecretory function, are invested by the pericapsular epithelium. Characteristically such cells bear several cilia. In these species and in Stylaria a pair of sensory cell groups is located anteriorly within the brain. These cells are ciliated but lack associated supporting cells."} {"id": "PMID:170710", "title": "Alveolar type II cells: studies on the mode of release of lamellar bodies.", "content": "There is increasing evidence that type II alveolar cells are capable of synthesizing surface active material like that obtained from the airways. However a number of problems remain to be solved before it can be stated conclusively that type II cells synthesize the surface active material of the terminal airspace. Among these problems is that of secretion. A number of previous studies have given evidence of the release of lamellar bodies by merocrine secretion. In this study morphologic evidence is presented which supports the view that secretion of lamellar bodies is accomplished by exocytosis. At the apical surface of type II cells, sites can be found where the limiting membrane of the lamellar body is clearly fused with the type II cell plasma membrane and an open channel exists between the contents of the lamellar body and the alveolar space. At these sites the lamellar contents extrude into the airspace with consequent loss of the highly compact organization of intracellular lamellar bodies. The intactness and continuity of the membranes can be traced for the full extent of the exocytosis site. Freeze-etch replicas of the membranes of type II cells show depressions which may represent the sites of discharged lamellae. In addition, tongue-like folds are seen which could be explained as the extensions of cytoplasm which surround the releasing lamellar body and which may flap over the exocytosis pit after discharge. Micrographs of the alveolar space show disorganized lamellar whorls which appear to be unravelling to produce tubular myelin. In view of the unusually large size and lipid composition of lamellar bodies, a mechanism involving hydration of mucopolysaccharide contents as an aid to expulsion of lamellar contents is suggested.", "contents": "Alveolar type II cells: studies on the mode of release of lamellar bodies. There is increasing evidence that type II alveolar cells are capable of synthesizing surface active material like that obtained from the airways. However a number of problems remain to be solved before it can be stated conclusively that type II cells synthesize the surface active material of the terminal airspace. Among these problems is that of secretion. A number of previous studies have given evidence of the release of lamellar bodies by merocrine secretion. In this study morphologic evidence is presented which supports the view that secretion of lamellar bodies is accomplished by exocytosis. At the apical surface of type II cells, sites can be found where the limiting membrane of the lamellar body is clearly fused with the type II cell plasma membrane and an open channel exists between the contents of the lamellar body and the alveolar space. At these sites the lamellar contents extrude into the airspace with consequent loss of the highly compact organization of intracellular lamellar bodies. The intactness and continuity of the membranes can be traced for the full extent of the exocytosis site. Freeze-etch replicas of the membranes of type II cells show depressions which may represent the sites of discharged lamellae. In addition, tongue-like folds are seen which could be explained as the extensions of cytoplasm which surround the releasing lamellar body and which may flap over the exocytosis pit after discharge. Micrographs of the alveolar space show disorganized lamellar whorls which appear to be unravelling to produce tubular myelin. In view of the unusually large size and lipid composition of lamellar bodies, a mechanism involving hydration of mucopolysaccharide contents as an aid to expulsion of lamellar contents is suggested."} {"id": "PMID:170711", "title": "Diagnostic value of intravenous glucagon test in insulinoma.", "content": "The intravenous glucagon test was performed in 11 patients with insulinoma and the diagnostic significance of the test was studied in comparison with the glucose test, the tolbutamide test and the arginine test. The curves of plasma insulin following the intravenous administration of glucagon were markedly different and strange in those patients with insulinoma compared with the normal controls. The maximal levels of plasma insulin ranged from 85 to 400 muU/ml, exceeding the normal range in 10 out of 11 patients, or 91%. Increased levels in the maximal plasma insulin were observed in 63%, 100% and 56% through the glucose test, the tolbutamide test and the arginine test, respectively. The distribution of the insulin areas, calculated from the insulin curves during these tests, was shown to be similar to that of the maximal levels of plasma insulin. There was no significant correlations between the maximal levels of plasma insulin in the glucagon test and the glucose test, the tolbutamide test or the arginine test. The present experiment demonstrated that the intravenous glucagon test, next to the tolbutamide test, caused a large increase in plasma insulin, and therefore, that this test is one of the most useful tools among the provocation tests, for the diagnosis of insulinoma.", "contents": "Diagnostic value of intravenous glucagon test in insulinoma. The intravenous glucagon test was performed in 11 patients with insulinoma and the diagnostic significance of the test was studied in comparison with the glucose test, the tolbutamide test and the arginine test. The curves of plasma insulin following the intravenous administration of glucagon were markedly different and strange in those patients with insulinoma compared with the normal controls. The maximal levels of plasma insulin ranged from 85 to 400 muU/ml, exceeding the normal range in 10 out of 11 patients, or 91%. Increased levels in the maximal plasma insulin were observed in 63%, 100% and 56% through the glucose test, the tolbutamide test and the arginine test, respectively. The distribution of the insulin areas, calculated from the insulin curves during these tests, was shown to be similar to that of the maximal levels of plasma insulin. There was no significant correlations between the maximal levels of plasma insulin in the glucagon test and the glucose test, the tolbutamide test or the arginine test. The present experiment demonstrated that the intravenous glucagon test, next to the tolbutamide test, caused a large increase in plasma insulin, and therefore, that this test is one of the most useful tools among the provocation tests, for the diagnosis of insulinoma."} {"id": "PMID:170712", "title": "Direct effects of cyclic AMP and dibutyryl cyclic AMP on renal blood flow.", "content": "The direct effects of adenosine 3',5'-cyclic monophosphate (cAMP) and dibutyryl adenosine 3',5'-cyclic monophosphate (D-cAMP) on renal blood flow were studied in dogs under renal perfusion with constant pressure. Cyclic AMP caused a marked phasic decrease in renal blood flow in doses more than 1 mg, while D-cAMP produced a slight increase in that in doses more than 10 mg. The vasoconstrictive effect of cAMP was not blocked by the pretreatment with phenoxybenzamine, but was markedly depressed during the infusion of aminophylline. On the other hand, the vasodilative effect of D-cAMP was not affected either by the pretreatment with propranolol or during the infusion of aminophylline. These findings indicate that cAMP and D-cAMP have an opposite direct effect on the renal artery, independently of the adrenergic receptors. However, there may be a possibility that cAMP produces its vasoconstrictive effect on the renal artery partly through the action of its metabolites.", "contents": "Direct effects of cyclic AMP and dibutyryl cyclic AMP on renal blood flow. The direct effects of adenosine 3',5'-cyclic monophosphate (cAMP) and dibutyryl adenosine 3',5'-cyclic monophosphate (D-cAMP) on renal blood flow were studied in dogs under renal perfusion with constant pressure. Cyclic AMP caused a marked phasic decrease in renal blood flow in doses more than 1 mg, while D-cAMP produced a slight increase in that in doses more than 10 mg. The vasoconstrictive effect of cAMP was not blocked by the pretreatment with phenoxybenzamine, but was markedly depressed during the infusion of aminophylline. On the other hand, the vasodilative effect of D-cAMP was not affected either by the pretreatment with propranolol or during the infusion of aminophylline. These findings indicate that cAMP and D-cAMP have an opposite direct effect on the renal artery, independently of the adrenergic receptors. However, there may be a possibility that cAMP produces its vasoconstrictive effect on the renal artery partly through the action of its metabolites."} {"id": "PMID:170715", "title": "[Demonstration of skeletal metastases using the bone marrow biopsy and the radiographic skeletal survey within the scope of pretherapeutic diagnosis in bronchial carcinoma].", "content": "In the course of pretherapeutic diagnostics of bronchogenic carcinoma, bone marrow biopsy revealed in ten out of 116 patients (9%) and radiographic skeletal survey in 16 out of 62 patients (26%) metastases to the skeleton. The two methods are complementary with reference to anaplastic and oat-cell carcinomas. On account of our experiences, we never fail to control the skeleton before the beginning of a local curative therapy in bronchial carcinoma.", "contents": "[Demonstration of skeletal metastases using the bone marrow biopsy and the radiographic skeletal survey within the scope of pretherapeutic diagnosis in bronchial carcinoma]. In the course of pretherapeutic diagnostics of bronchogenic carcinoma, bone marrow biopsy revealed in ten out of 116 patients (9%) and radiographic skeletal survey in 16 out of 62 patients (26%) metastases to the skeleton. The two methods are complementary with reference to anaplastic and oat-cell carcinomas. On account of our experiences, we never fail to control the skeleton before the beginning of a local curative therapy in bronchial carcinoma."} {"id": "PMID:170716", "title": "The effect of dianabol on the postirradiation disturbances of kininogenesis in rats.", "content": "The effect of Dianabol on the irradiation-induced disturbances in kininogenesis in rats was studied. It was found that Dianabol inhibits the postradiation increase of the kininforming activity in tissues of rats and decreases the level of kinins in irradiated animals. A probable role of these properties of Dianabol in its radioprotective activity is discussed.", "contents": "The effect of dianabol on the postirradiation disturbances of kininogenesis in rats. The effect of Dianabol on the irradiation-induced disturbances in kininogenesis in rats was studied. It was found that Dianabol inhibits the postradiation increase of the kininforming activity in tissues of rats and decreases the level of kinins in irradiated animals. A probable role of these properties of Dianabol in its radioprotective activity is discussed."} {"id": "PMID:170719", "title": "Evidence for two cell populations involved in the rejection of a xenograft in mice.", "content": "Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal cell population. By using two in vitro assays in parallel, it has been possible to show that there are at least two active cell types. The first assay detects the detachment of target cells from plastic, which is referred to as direct cytotoxicity. The second reflects the inhibition of incorporation of a deoxyribonucleic acid precursor, 125I-iododeoxyuridine, into target cells, which could occur either as a result of direct cytotoxicity or as a consequence of growth inhibition (cytostasis). With a rabbit antimouse brain serum which is cytotoxic for thymus-derived T cells, it has been shown that direct cytotoxicity requires T cells, whereas the cytostatic response can be largely independent of T cell function during the assay.", "contents": "Evidence for two cell populations involved in the rejection of a xenograft in mice. Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal cell population. By using two in vitro assays in parallel, it has been possible to show that there are at least two active cell types. The first assay detects the detachment of target cells from plastic, which is referred to as direct cytotoxicity. The second reflects the inhibition of incorporation of a deoxyribonucleic acid precursor, 125I-iododeoxyuridine, into target cells, which could occur either as a result of direct cytotoxicity or as a consequence of growth inhibition (cytostasis). With a rabbit antimouse brain serum which is cytotoxic for thymus-derived T cells, it has been shown that direct cytotoxicity requires T cells, whereas the cytostatic response can be largely independent of T cell function during the assay."} {"id": "PMID:170721", "title": "[Ultrastructure of the nuclear apparatus of the infusorian Loxodes magnus. I. The macronuclei, macronuclear anlagen and the interphasic micronuclei].", "content": "The nuclear apparatus of Loxodes magnus Stokes (Holotricha) consists of numerous macronuclei which belong to the diploid type and never divide, and of numerous micronuclei. No nuclear groups exist; individual nuclei often lie in cytoplasmic islets surrounded by large lacunae of the smooth endoplasmic reticulum. Interphasic micronuclei have two-membraned envelopes with numerous pores, usually lined at the cytoplasmic side with a layer of vacuoles, channels, or flattened vesicles of the smooth endoplasmic reticulum. The chromatin of the micronuclei consists of anastomosing threads, 0.1--0.2 mum wide, between which several nucleolus-like bodies of microfibrillar structure occur. Adult macronuclei have a similar nuclear envelope and a similar system of vacuoles, channels, and flattened agranular cisternae outside it. The macronucleus contains a single large composite nucleolus with 3 or 4 fibrillar cores inside the common granular cortex. The fibrillar cores are pierced by channels containing nucleolar organizers in the form of strands of condensed chromatin. The peripheral zone of the macronucleus is filled with decondensed chromatin fibrils and contains a number of small chromocenters and several aggregates of RNP granules. No protein inclusions (spheres) have been observed in Loxodes macronuclei. The macronuclear anlagen, developing in the cycle of every cell division, show progressive decondensation of the chromosomes and formation of several nucleoli, each with its own organizer. Later on, the nucleoli fuse into a single nucleolus. The small chromocentres are the last to form.", "contents": "[Ultrastructure of the nuclear apparatus of the infusorian Loxodes magnus. I. The macronuclei, macronuclear anlagen and the interphasic micronuclei]. The nuclear apparatus of Loxodes magnus Stokes (Holotricha) consists of numerous macronuclei which belong to the diploid type and never divide, and of numerous micronuclei. No nuclear groups exist; individual nuclei often lie in cytoplasmic islets surrounded by large lacunae of the smooth endoplasmic reticulum. Interphasic micronuclei have two-membraned envelopes with numerous pores, usually lined at the cytoplasmic side with a layer of vacuoles, channels, or flattened vesicles of the smooth endoplasmic reticulum. The chromatin of the micronuclei consists of anastomosing threads, 0.1--0.2 mum wide, between which several nucleolus-like bodies of microfibrillar structure occur. Adult macronuclei have a similar nuclear envelope and a similar system of vacuoles, channels, and flattened agranular cisternae outside it. The macronucleus contains a single large composite nucleolus with 3 or 4 fibrillar cores inside the common granular cortex. The fibrillar cores are pierced by channels containing nucleolar organizers in the form of strands of condensed chromatin. The peripheral zone of the macronucleus is filled with decondensed chromatin fibrils and contains a number of small chromocenters and several aggregates of RNP granules. No protein inclusions (spheres) have been observed in Loxodes macronuclei. The macronuclear anlagen, developing in the cycle of every cell division, show progressive decondensation of the chromosomes and formation of several nucleoli, each with its own organizer. Later on, the nucleoli fuse into a single nucleolus. The small chromocentres are the last to form."} {"id": "PMID:170722", "title": "[Some characteristics of the process of forming autophagocytic vacuoles in the hepatocytes of regenerating rat liver].", "content": "This work deals with the previously described process of cellular autophagocytosis in regenerating rat liver. The experimental data obtained indicate that the early appearance of acid phosphatase positive cytoplasmic vacuoles (with diameter more than 2 mu) occur only in a certain portion of the parenchymal cell population (nearly 30% of the total number of hepatocytes) and mainly in the central area of the hepatic lobule. It may be concluded that the observed reaction of the cell vacuolar apparatus concerns hepatocytes that undergo the entry into the mitotic cycle much later than does the main part (ca 60%) of cell population.", "contents": "[Some characteristics of the process of forming autophagocytic vacuoles in the hepatocytes of regenerating rat liver]. This work deals with the previously described process of cellular autophagocytosis in regenerating rat liver. The experimental data obtained indicate that the early appearance of acid phosphatase positive cytoplasmic vacuoles (with diameter more than 2 mu) occur only in a certain portion of the parenchymal cell population (nearly 30% of the total number of hepatocytes) and mainly in the central area of the hepatic lobule. It may be concluded that the observed reaction of the cell vacuolar apparatus concerns hepatocytes that undergo the entry into the mitotic cycle much later than does the main part (ca 60%) of cell population."} {"id": "PMID:170720", "title": "[Structure of Candida tropicalis K-41 thermotolerant yeasts at various growing temperatures on a mineral medium with hydrocarbons].", "content": "In the C. tropicalis K-41 cells fixed by glutaraldehyde and osmium most membranes consisted of two electron-transparent and one electron-dense layer. Morphologo-structural peculiarities of the cell fraction grown at 39 degrees testify to a certain disconnection of energetic and constructive metabolism, inhibition of synthetic processes. Cell division was more active at 29 degrees.", "contents": "[Structure of Candida tropicalis K-41 thermotolerant yeasts at various growing temperatures on a mineral medium with hydrocarbons]. In the C. tropicalis K-41 cells fixed by glutaraldehyde and osmium most membranes consisted of two electron-transparent and one electron-dense layer. Morphologo-structural peculiarities of the cell fraction grown at 39 degrees testify to a certain disconnection of energetic and constructive metabolism, inhibition of synthetic processes. Cell division was more active at 29 degrees."} {"id": "PMID:170727", "title": "Structure of cultured fibroblasts from dermatosparaxic calves.", "content": "Clonal cell lines from the dermis of a dermatosparaxic calf were grown in tissue culture. After fixation in a mixture of glutaraldehyde and osmium, they were prepared for electron microscopy. Most cells contained a well-developed Golgi region, lysosomes, mitochondria, and dilated cisternae of rough endoplasmic reticulum. They also contained numerous, large bundles of intracellular fialments, many lipid droplets and extensive arrays of vesicles. Cultures accumulated substantial amounts of extracellular fibrillar material. The fibrils were loosely packed and indistinctly cross-banded. Bundles of intracellular filaments were commonly parallel in adjacent cells and also parallel to extracellular fibrils. These cytoplasmic features may result from the inability of the secreted collagen to form normal fibrils.", "contents": "Structure of cultured fibroblasts from dermatosparaxic calves. Clonal cell lines from the dermis of a dermatosparaxic calf were grown in tissue culture. After fixation in a mixture of glutaraldehyde and osmium, they were prepared for electron microscopy. Most cells contained a well-developed Golgi region, lysosomes, mitochondria, and dilated cisternae of rough endoplasmic reticulum. They also contained numerous, large bundles of intracellular fialments, many lipid droplets and extensive arrays of vesicles. Cultures accumulated substantial amounts of extracellular fibrillar material. The fibrils were loosely packed and indistinctly cross-banded. Bundles of intracellular filaments were commonly parallel in adjacent cells and also parallel to extracellular fibrils. These cytoplasmic features may result from the inability of the secreted collagen to form normal fibrils."} {"id": "PMID:170729", "title": "Pancreatic cholera (W.D.H.A. syndrome). Histochemical and ultrastructural studies.", "content": "Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C.", "contents": "Pancreatic cholera (W.D.H.A. syndrome). Histochemical and ultrastructural studies. Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C."} {"id": "PMID:170730", "title": "Morphogenesis of intracytoplasmic dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. Light- and electron-microscopic investigations.", "content": "This study presents the results of light-microscopic, histochemical, and electron-microscopic investigations of dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. At ultrastructural level it was possible to observe several stages of development correlated with changes of ergastoplasmic reticulum. The viral nature of these bodies was refuted and the conclusion was drawn that their formation is associated with a disturbed intracellular metabolism. The defective intracellular transport of collagen precursors followed by abnormal deposition of collagenous proteins, which are also to some extent abnormally aggregated, could be of special importance.", "contents": "Morphogenesis of intracytoplasmic dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. Light- and electron-microscopic investigations. This study presents the results of light-microscopic, histochemical, and electron-microscopic investigations of dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. At ultrastructural level it was possible to observe several stages of development correlated with changes of ergastoplasmic reticulum. The viral nature of these bodies was refuted and the conclusion was drawn that their formation is associated with a disturbed intracellular metabolism. The defective intracellular transport of collagen precursors followed by abnormal deposition of collagenous proteins, which are also to some extent abnormally aggregated, could be of special importance."} {"id": "PMID:170731", "title": "Changes in the fine structure and function of a hormone-secreting adrenocortical tumour investigated in tissue culture.", "content": "Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipid-rich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production.", "contents": "Changes in the fine structure and function of a hormone-secreting adrenocortical tumour investigated in tissue culture. Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipid-rich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production."} {"id": "PMID:170732", "title": "Cellular composition of the so-called dermatofibroma (histiocytoma cutis).", "content": "9 typical cases of dermatofibroma or histiocytoma cutis resp. were studied by the aid of histochemical, enzyme histochemical and electron microscopical methods to examine the cellular composition of these lesions. The results suggest an anabolic and katabolic function of cells. Electron microscopically a broad spectrum of patterns of mesenchymal cells was found. Besides defined fibroblast-like and histiocyte-like elements a cell type was detected which was characterized by particular traits, as irregular nuclear outline, abundant rough endoplasmic reticulum, free ribosomes, bundles of filaments with single dense zones, micropinocytotic vesicles and a basement membrane-like material on the outer cell surface. This cell type constitutes the majority of cells in dermatofibroma or histiocytoma cutis resp. In some cells an arrangement of filament bundles resembling that in smooth muscle could be seen. By reason of these findings a certain resemblance to the so-called myofibroblasts can be stated. The variegation of the morphological picture suggests a multipotent precursor cell; the possibility of an origin from pericytes is discussed.", "contents": "Cellular composition of the so-called dermatofibroma (histiocytoma cutis). 9 typical cases of dermatofibroma or histiocytoma cutis resp. were studied by the aid of histochemical, enzyme histochemical and electron microscopical methods to examine the cellular composition of these lesions. The results suggest an anabolic and katabolic function of cells. Electron microscopically a broad spectrum of patterns of mesenchymal cells was found. Besides defined fibroblast-like and histiocyte-like elements a cell type was detected which was characterized by particular traits, as irregular nuclear outline, abundant rough endoplasmic reticulum, free ribosomes, bundles of filaments with single dense zones, micropinocytotic vesicles and a basement membrane-like material on the outer cell surface. This cell type constitutes the majority of cells in dermatofibroma or histiocytoma cutis resp. In some cells an arrangement of filament bundles resembling that in smooth muscle could be seen. By reason of these findings a certain resemblance to the so-called myofibroblasts can be stated. The variegation of the morphological picture suggests a multipotent precursor cell; the possibility of an origin from pericytes is discussed."} {"id": "PMID:170733", "title": "Ruptured benign hepatoma associated with an oral contraceptive. A case report.", "content": "A ruptured benign hepatoma is described in a woman at full-term pregnancy. The patient had used an oral contraceptive for eight years before she became pregnant. According to several recent reports it seems likely that there is a relationship between the use of oral contraceptive agents and the development of liver cell tumours. Twentythree such cases have been found in the literature. Fourteen of these were not diagnosed before rupture. The present tumour differed from previously described lesions by containing foci of haematopoietic cells. As there were no signs of blood or bone marrow disease, it is suggested that the extramedullary haematopoiesis is a constituent of the tumour tissue.", "contents": "Ruptured benign hepatoma associated with an oral contraceptive. A case report. A ruptured benign hepatoma is described in a woman at full-term pregnancy. The patient had used an oral contraceptive for eight years before she became pregnant. According to several recent reports it seems likely that there is a relationship between the use of oral contraceptive agents and the development of liver cell tumours. Twentythree such cases have been found in the literature. Fourteen of these were not diagnosed before rupture. The present tumour differed from previously described lesions by containing foci of haematopoietic cells. As there were no signs of blood or bone marrow disease, it is suggested that the extramedullary haematopoiesis is a constituent of the tumour tissue."} {"id": "PMID:170734", "title": "Distribution of cytoplasmic vacuoles in blood T and B lymphocytes in two lysosomal disorders.", "content": "Distribution of cytoplasmic vacuoles in purified T and B lymphocytes was analyzed in four cases of aspartylglucosaminuria (AGU) and in one case of neuronal ceroid lipofuscinosis (Spielmeyer-Sj\u00f6rgren type). In all cases T cells were significantly more vacuolized than B cells. The ultrastructure of the cytoplasmic vacuoles was consistent with the concept of storage lysosomes. The cytoplasmic vacuoles both in T and B cells similar to abnormal lysosomes seen in the visceral organs in these diseases.", "contents": "Distribution of cytoplasmic vacuoles in blood T and B lymphocytes in two lysosomal disorders. Distribution of cytoplasmic vacuoles in purified T and B lymphocytes was analyzed in four cases of aspartylglucosaminuria (AGU) and in one case of neuronal ceroid lipofuscinosis (Spielmeyer-Sj\u00f6rgren type). In all cases T cells were significantly more vacuolized than B cells. The ultrastructure of the cytoplasmic vacuoles was consistent with the concept of storage lysosomes. The cytoplasmic vacuoles both in T and B cells similar to abnormal lysosomes seen in the visceral organs in these diseases."} {"id": "PMID:170735", "title": "Stimulation of cellular autophagy by parathyroid hormone and cyclic adenosine 3',5': monophosphate in isolated tubular fragments from the rat's kidney cortex.", "content": "Tubular fragments isolated from the cortex of the rat's kidney were qualitatively and quantitatively investigated with the electron microscope. The tubules frequently burst open and became \"inverted\" in such a way that the rarefied brush border now formed the outer circumference. By morphometry a decrease of the average cell volume in the proximal tubular fragments was ascertained. This was mostly caused by a loss of cytoplasmic ground substance, endoplasmic reticulum and ribosomes. Cytoplasmic herniations of the basal surface, filled with free ribosomes, suggested a partial shedding of the protein synthesizing apparatus. The number of autophagic vacuoles (AV) per unit area of cytoplasm was determined in proximal tubular fragments. After isolation alone, without further incubation, the number of AV was as low as the number found in an earlier study in proximal tubular cells in situ during the diurnal minimum. After control incubation the number of AV increased to about the mean value of the AV found in cells in situ during the whole diurnal cycle. By comparison with the control incubation the number of AV increased by a factor of 1.6 to 1.7, if cyclic adenosine 3',5': monophosphate (cyclic AMP) or parathyroid hormone (PTH) were added to the incubation-medium; it now reached about the number of AV found in situ during the diurnal maximum. The increase in the number of AV paralleled that of the production of ammonia and glucose from endogenous sources under the influence of cyclic AMP and PTH. This suggests that the breakdown of cytoplasmic components by cellular autophagy could be functionally related to gluconeogenesis. A quantitative comparison between the measured production of ammonia and glucose indicates, however, that in the system of isolated tubular fragments there may exist other mechanisms of degradation, and of the provision of substrates for gluconeogenesis, than cellular autophagy only.", "contents": "Stimulation of cellular autophagy by parathyroid hormone and cyclic adenosine 3',5': monophosphate in isolated tubular fragments from the rat's kidney cortex. Tubular fragments isolated from the cortex of the rat's kidney were qualitatively and quantitatively investigated with the electron microscope. The tubules frequently burst open and became \"inverted\" in such a way that the rarefied brush border now formed the outer circumference. By morphometry a decrease of the average cell volume in the proximal tubular fragments was ascertained. This was mostly caused by a loss of cytoplasmic ground substance, endoplasmic reticulum and ribosomes. Cytoplasmic herniations of the basal surface, filled with free ribosomes, suggested a partial shedding of the protein synthesizing apparatus. The number of autophagic vacuoles (AV) per unit area of cytoplasm was determined in proximal tubular fragments. After isolation alone, without further incubation, the number of AV was as low as the number found in an earlier study in proximal tubular cells in situ during the diurnal minimum. After control incubation the number of AV increased to about the mean value of the AV found in cells in situ during the whole diurnal cycle. By comparison with the control incubation the number of AV increased by a factor of 1.6 to 1.7, if cyclic adenosine 3',5': monophosphate (cyclic AMP) or parathyroid hormone (PTH) were added to the incubation-medium; it now reached about the number of AV found in situ during the diurnal maximum. The increase in the number of AV paralleled that of the production of ammonia and glucose from endogenous sources under the influence of cyclic AMP and PTH. This suggests that the breakdown of cytoplasmic components by cellular autophagy could be functionally related to gluconeogenesis. A quantitative comparison between the measured production of ammonia and glucose indicates, however, that in the system of isolated tubular fragments there may exist other mechanisms of degradation, and of the provision of substrates for gluconeogenesis, than cellular autophagy only."} {"id": "PMID:170742", "title": "[Treatment of patients with lung cancer with a combination of nitrosomethylurea and cyclophosphane].", "content": "Eighty five patients with pulmonary cancer, stage III-IV, were treated with a combination of nitrosomethyl urea and cyclophosphan. In squamous cell cancer a positive objective effect was gained in 35% of patients.", "contents": "[Treatment of patients with lung cancer with a combination of nitrosomethylurea and cyclophosphane]. Eighty five patients with pulmonary cancer, stage III-IV, were treated with a combination of nitrosomethyl urea and cyclophosphan. In squamous cell cancer a positive objective effect was gained in 35% of patients."} {"id": "PMID:170744", "title": "[Intrauterine transmission of induced hemoblastosis in monkeys, associated with type-C oncornavirus].", "content": "The possibility of intrauterine transmission of hemoblastosis was investigated in a group of 118 M. arctoides females with induced viral hemoblastosis. In the course of observations pregnancy occurred in 9 cases. Four of seven babies, delivered at term have developed hemoblastosis. The main signs of the disease were revealed in babies from the first days of their life. Hemoblastosis was accompanied with the appearance of a specific surface antigen and the presence of the \"C\" type oncornavirus in blood and organs of the babies, and also in cells of one embryo. Viral hemoblastosis was successfully passaged from one of the babies to three juvenile monkeys of the same species.", "contents": "[Intrauterine transmission of induced hemoblastosis in monkeys, associated with type-C oncornavirus]. The possibility of intrauterine transmission of hemoblastosis was investigated in a group of 118 M. arctoides females with induced viral hemoblastosis. In the course of observations pregnancy occurred in 9 cases. Four of seven babies, delivered at term have developed hemoblastosis. The main signs of the disease were revealed in babies from the first days of their life. Hemoblastosis was accompanied with the appearance of a specific surface antigen and the presence of the \"C\" type oncornavirus in blood and organs of the babies, and also in cells of one embryo. Viral hemoblastosis was successfully passaged from one of the babies to three juvenile monkeys of the same species."} {"id": "PMID:170750", "title": "Altered immunologic specificity of cells infected with Herpes simplex virus: recognition of human antiserum.", "content": "Human serum having complement fixation anti-herpex simplex virus activity was reacted with herpes simplex virus infected cells in tissue culture. By tagging the antibody to ferritin and examining the cells in the electron microscope, it was found that 1. the entire surface of the infected cell is antigenically altered and reacts with hyperimmune serum. The antigenic cell surface change is not limited to structurally altered sites, nor is it limited to sites where virus particles are present, and 2. cells in the early stages of infection react more strongly with hyperimmune serum than do cells in later stages. The possible clinical significance of the infected cell surface - antibody reaction is discussed.", "contents": "Altered immunologic specificity of cells infected with Herpes simplex virus: recognition of human antiserum. Human serum having complement fixation anti-herpex simplex virus activity was reacted with herpes simplex virus infected cells in tissue culture. By tagging the antibody to ferritin and examining the cells in the electron microscope, it was found that 1. the entire surface of the infected cell is antigenically altered and reacts with hyperimmune serum. The antigenic cell surface change is not limited to structurally altered sites, nor is it limited to sites where virus particles are present, and 2. cells in the early stages of infection react more strongly with hyperimmune serum than do cells in later stages. The possible clinical significance of the infected cell surface - antibody reaction is discussed."} {"id": "PMID:170751", "title": "Respiratory electron flow and ATPase system in photosynthetically grown Rhodopseudomonas palustris.", "content": "Rhodopseudomonas palustris is grown photosynthetically on thiosulfate. As pointed out earlier, the chromatophore deficient cell-free fraction S-144,000 catalyzes the thiosulfate-linked ATP-dependent reversal of electron transfer in anaerobiosis, thus providing reducing equivalents in the form of NADH. Under aerobic conditions, this fraction also catalyzes the oxidation of NADH, ferro-cytochrome c, or ascorbate. ATP, ADP, and PPi are active in retarding the aerobic electron flow. The electron retardation is stimulated by the addition of Mg2+ due to a Mg2+-stimulated ATPase present. The ATPase system in S-144,000 hydrolyzes ATP, ADP, and PPi. Similarly, ATP or ADP, or even PPi can function as energy sources in order to achieve the reduction of pyridine nucleotide. The ATPase turnover is diminished by NADH or NAD+. Admixture of ascorbate results in an increased ATPase activity. Exactly the enhanced amount of adenine nucleotide hydrolysis caused by the addition of ascorbate is inhibited by cyanide.", "contents": "Respiratory electron flow and ATPase system in photosynthetically grown Rhodopseudomonas palustris. Rhodopseudomonas palustris is grown photosynthetically on thiosulfate. As pointed out earlier, the chromatophore deficient cell-free fraction S-144,000 catalyzes the thiosulfate-linked ATP-dependent reversal of electron transfer in anaerobiosis, thus providing reducing equivalents in the form of NADH. Under aerobic conditions, this fraction also catalyzes the oxidation of NADH, ferro-cytochrome c, or ascorbate. ATP, ADP, and PPi are active in retarding the aerobic electron flow. The electron retardation is stimulated by the addition of Mg2+ due to a Mg2+-stimulated ATPase present. The ATPase system in S-144,000 hydrolyzes ATP, ADP, and PPi. Similarly, ATP or ADP, or even PPi can function as energy sources in order to achieve the reduction of pyridine nucleotide. The ATPase turnover is diminished by NADH or NAD+. Admixture of ascorbate results in an increased ATPase activity. Exactly the enhanced amount of adenine nucleotide hydrolysis caused by the addition of ascorbate is inhibited by cyanide."} {"id": "PMID:170755", "title": "Ultrastructure of Trypanosoma duttoni.", "content": "Trypanosoma duttoni exhibits the typical trypanosome morphology in that it is bounded by a unit membrane which included its anterior flagellum; it is surrounded by a framework of suppellicular fibrils, and it contains a nucleus and the posteriorly located kinetoplast-blepharoplast structures along with cytoplasmic organelles (mitochondria, Golgi, and enoplasmic reticulum). Very prominently displayed in T. duttoni is the contractile vacuole, which has not previously received wide-spread recognition. The kinetoplast is clearly continuous with mitochondria in some cases. Inclusion bodies are categorized into three distinct types, none of which can be conclusively designated as the very popular volutin granules, without cytochemical evidence. The existence of a third tubule among peripheral tubule doublets of the flagellum is observed.", "contents": "Ultrastructure of Trypanosoma duttoni. Trypanosoma duttoni exhibits the typical trypanosome morphology in that it is bounded by a unit membrane which included its anterior flagellum; it is surrounded by a framework of suppellicular fibrils, and it contains a nucleus and the posteriorly located kinetoplast-blepharoplast structures along with cytoplasmic organelles (mitochondria, Golgi, and enoplasmic reticulum). Very prominently displayed in T. duttoni is the contractile vacuole, which has not previously received wide-spread recognition. The kinetoplast is clearly continuous with mitochondria in some cases. Inclusion bodies are categorized into three distinct types, none of which can be conclusively designated as the very popular volutin granules, without cytochemical evidence. The existence of a third tubule among peripheral tubule doublets of the flagellum is observed."} {"id": "PMID:170752", "title": "A study of the neurohumoral control of glycolysis in the mouse brain in vivo: role of noradrenaline and dopamine.", "content": "Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of \"free\" glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with alpha-methyl-p-tyrosin. DL-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or by antagonizing the effect of 3,5-cyclic adenosine monophosphate on glycolysis.", "contents": "A study of the neurohumoral control of glycolysis in the mouse brain in vivo: role of noradrenaline and dopamine. Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of \"free\" glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with alpha-methyl-p-tyrosin. DL-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or by antagonizing the effect of 3,5-cyclic adenosine monophosphate on glycolysis."} {"id": "PMID:170756", "title": "[The anatomic and radiologic picture of the acetabulum (author's transl)].", "content": "The basic shape of the facies lunata shows at the inner margin of each of the three participating bones a dell into which the floor of the acetabulum progresses. These dells originate in nutritive vessels which enter the bone and claim this place. There always are groups of vessels and wide channels which may be visible on radiographs. The so far unexplained picture of a vascular canal in the roof of the acetabulum corresponds to the canal leading into the body of the ilium. Due to its position there is often restructuring leading to filling or covering of the canal. The entrance to this canal is shown as a gap in the arc of the acetabular cavity which would have to be added to that of the \"tear figure\" known so far. The closed arc, as always drawn, reults only when this entry has been filled up.", "contents": "[The anatomic and radiologic picture of the acetabulum (author's transl)]. The basic shape of the facies lunata shows at the inner margin of each of the three participating bones a dell into which the floor of the acetabulum progresses. These dells originate in nutritive vessels which enter the bone and claim this place. There always are groups of vessels and wide channels which may be visible on radiographs. The so far unexplained picture of a vascular canal in the roof of the acetabulum corresponds to the canal leading into the body of the ilium. Due to its position there is often restructuring leading to filling or covering of the canal. The entrance to this canal is shown as a gap in the arc of the acetabular cavity which would have to be added to that of the \"tear figure\" known so far. The closed arc, as always drawn, reults only when this entry has been filled up."} {"id": "PMID:170757", "title": "[Postsurgical management of cutaneous syndactyly (author's transl)].", "content": "The success of syndactyly operations depends to a considerable extent on the appropriate bandage-technique which according to the author's experience has proved to be highly effective.", "contents": "[Postsurgical management of cutaneous syndactyly (author's transl)]. The success of syndactyly operations depends to a considerable extent on the appropriate bandage-technique which according to the author's experience has proved to be highly effective."} {"id": "PMID:170753", "title": "In vitro translation of natural mRNAs in a cell-free system containing components from interferon-treated chicken fibroblasts and factor preparations from mouse ascites cells or rabbit reticulocytes.", "content": "The effect of interferon has been studied in a mixed cell-free protein synthesizing system. Hemoglobin (Hb) and Encephalomyocarditis virus (EMC)-RNA can be efficiently translated in vitro in a system containing S-30 lysates or run-off ribosomes from primary chick embryo fibroblasts (CEF) and a postmicrosomal supernatant from mouse ascites cells or a ribosomal-wash preparation from rabbit reticulocytes. Ribosomes prepared from CEF pretreated with high doses of homologous interferon (500 units/ml) were able to translate Hb-RNA in the presence of heterologous factors with the same efficiency as ribosomes prepared from control cells. Translation of EMC-RNAP WAS SLIGHTLY Reduced if ribosomes from interferon-treated cells were used in the mixed cell-free system, confirming previous reports. No inhibitory effect caused by interferon treatment of CEF cells could be detected on in vitro translation of natural mRNAs if the cells had, in addition to interferon treatment, been infected with vaccinia virus. Possible reasons for the different observations made with out cell-free protein synthesizing system from CEF and with cell-free systems prepared from mouse cells are discussed.", "contents": "In vitro translation of natural mRNAs in a cell-free system containing components from interferon-treated chicken fibroblasts and factor preparations from mouse ascites cells or rabbit reticulocytes. The effect of interferon has been studied in a mixed cell-free protein synthesizing system. Hemoglobin (Hb) and Encephalomyocarditis virus (EMC)-RNA can be efficiently translated in vitro in a system containing S-30 lysates or run-off ribosomes from primary chick embryo fibroblasts (CEF) and a postmicrosomal supernatant from mouse ascites cells or a ribosomal-wash preparation from rabbit reticulocytes. Ribosomes prepared from CEF pretreated with high doses of homologous interferon (500 units/ml) were able to translate Hb-RNA in the presence of heterologous factors with the same efficiency as ribosomes prepared from control cells. Translation of EMC-RNAP WAS SLIGHTLY Reduced if ribosomes from interferon-treated cells were used in the mixed cell-free system, confirming previous reports. No inhibitory effect caused by interferon treatment of CEF cells could be detected on in vitro translation of natural mRNAs if the cells had, in addition to interferon treatment, been infected with vaccinia virus. Possible reasons for the different observations made with out cell-free protein synthesizing system from CEF and with cell-free systems prepared from mouse cells are discussed."} {"id": "PMID:170754", "title": "On the phospholipase activity in bovine seminal vesicles and its possible role in the regulation of the prostaglandin biosynthesis.", "content": "A phospholipid mixture was isolated from bovine vesicle tissue. This phospholipid preparation contained the following prostaglandin precursor fatty acids: 4.7 percent 5,8,11-eicosatrienoic acid, 9.1 percent 5,8,11,14-eicosatetraenoic acid and 0.9% 5,8,11,14,17-eicosapentaenoic acid. With this phospholipid preparation as substrate phospholipase activity could be detected in different fractions of bovine seminal vesicle cells. The highest phospholipase activity was found in the microsomal fraction, less in the mitochondria and essentially no activity in the cytosol. With a microsome preparation (acetone powder) of bovine seminal vesicles the influence of certain effectors on the phospholipase activity was investigated. Prostaglandins E2 and F2alpha (10(-5) M) showed 19 and 41 percent inhibition, DB-c-AMP (2 times 10(-9) M) 54%, c-AMP (10(-9) M) 22%, epinephrine (10(-4) M) 60%, testosterone (10(-5) M) 25% inhibition of the phospholipase activity. Whereas ethanol exhibits also a strong inhibition on the phospholipase activity, it shows a pronounced activation of the prostaglandin synthetase.", "contents": "On the phospholipase activity in bovine seminal vesicles and its possible role in the regulation of the prostaglandin biosynthesis. A phospholipid mixture was isolated from bovine vesicle tissue. This phospholipid preparation contained the following prostaglandin precursor fatty acids: 4.7 percent 5,8,11-eicosatrienoic acid, 9.1 percent 5,8,11,14-eicosatetraenoic acid and 0.9% 5,8,11,14,17-eicosapentaenoic acid. With this phospholipid preparation as substrate phospholipase activity could be detected in different fractions of bovine seminal vesicle cells. The highest phospholipase activity was found in the microsomal fraction, less in the mitochondria and essentially no activity in the cytosol. With a microsome preparation (acetone powder) of bovine seminal vesicles the influence of certain effectors on the phospholipase activity was investigated. Prostaglandins E2 and F2alpha (10(-5) M) showed 19 and 41 percent inhibition, DB-c-AMP (2 times 10(-9) M) 54%, c-AMP (10(-9) M) 22%, epinephrine (10(-4) M) 60%, testosterone (10(-5) M) 25% inhibition of the phospholipase activity. Whereas ethanol exhibits also a strong inhibition on the phospholipase activity, it shows a pronounced activation of the prostaglandin synthetase."} {"id": "PMID:170759", "title": "Virological studies on gynaecological patients.", "content": "Endometrial epithelial cells and blood samples taken simultaneously with the curettage (first serum) of 138 patients suffering from menstrual bleeding disorders as well as materials obtained from 16 induced abortions, were studied for the presence of virus. Fourteen adenovirus 2 strains were isolated from samples of the patients. Endometrial epithelial cells of 35 patients were examined with immunofluorescence method and 23 of them displayed specific fluorescence referring to the presence of viral antigens, with adenovirus and herpesvirus antisera. Studying withserological reactions the first and second (convalescent) sera of patients, high titers were found against type 2 herpesvirus in both sera, and titer rise against the latent adenovirus types in the second sera. Neither infective virus nor the presence of viral antigens were demonstrable in materials obtained from induced abortions.", "contents": "Virological studies on gynaecological patients. Endometrial epithelial cells and blood samples taken simultaneously with the curettage (first serum) of 138 patients suffering from menstrual bleeding disorders as well as materials obtained from 16 induced abortions, were studied for the presence of virus. Fourteen adenovirus 2 strains were isolated from samples of the patients. Endometrial epithelial cells of 35 patients were examined with immunofluorescence method and 23 of them displayed specific fluorescence referring to the presence of viral antigens, with adenovirus and herpesvirus antisera. Studying withserological reactions the first and second (convalescent) sera of patients, high titers were found against type 2 herpesvirus in both sera, and titer rise against the latent adenovirus types in the second sera. Neither infective virus nor the presence of viral antigens were demonstrable in materials obtained from induced abortions."} {"id": "PMID:170760", "title": "[Early bacteriological diagnosis of infections after osteosynthesis (author's transl)].", "content": "Postoperative infections after osteosynthesis belong to the most serious complications in traumatology. Efforts to prevent this danger by routine antibiotic prophylaxis are mainly rejected nowadays. Instead, it is studies whether infections can be diagnosed by bacteriological culture of secretions from Redon drains in patients with osteosynthesis for the purpose of starting an early specific antibiotic therapy. Bacteria were cultured from secretions of wounds in 11.3% of samples from 177 patients. Staph. aureus was found most frequently and was responsible for most of the postoperative infections (Tab. 1).", "contents": "[Early bacteriological diagnosis of infections after osteosynthesis (author's transl)]. Postoperative infections after osteosynthesis belong to the most serious complications in traumatology. Efforts to prevent this danger by routine antibiotic prophylaxis are mainly rejected nowadays. Instead, it is studies whether infections can be diagnosed by bacteriological culture of secretions from Redon drains in patients with osteosynthesis for the purpose of starting an early specific antibiotic therapy. Bacteria were cultured from secretions of wounds in 11.3% of samples from 177 patients. Staph. aureus was found most frequently and was responsible for most of the postoperative infections (Tab. 1)."} {"id": "PMID:170762", "title": "[Uremic polyneuropathies].", "content": "The report is concerned with the results of a study of polyneuropathy in 75 patients with acute and chronic renal insufficiency. The authors described the clinical characteristics of the different forms of neuropathy. In acute renal insufficiency the first signs of polyneuropathy appear during the stage of polyuria and are reversible. In chronic renal insufficiency and hemodialysis treatment of subclinical an sensory forms of neuropathy are mainly seen (2/3 of the patients). It was demonstrated that there was a retardation in the velocity of excitative conductivity through the nerves depending upon the severity of polyneuropathy. A longterm adequate hemodialysis may prevent the further development of polyneuropathy.", "contents": "[Uremic polyneuropathies]. The report is concerned with the results of a study of polyneuropathy in 75 patients with acute and chronic renal insufficiency. The authors described the clinical characteristics of the different forms of neuropathy. In acute renal insufficiency the first signs of polyneuropathy appear during the stage of polyuria and are reversible. In chronic renal insufficiency and hemodialysis treatment of subclinical an sensory forms of neuropathy are mainly seen (2/3 of the patients). It was demonstrated that there was a retardation in the velocity of excitative conductivity through the nerves depending upon the severity of polyneuropathy. A longterm adequate hemodialysis may prevent the further development of polyneuropathy."} {"id": "PMID:170763", "title": "[State of the cerebral and peripheral blood circulation in chronic neurotoxoplasmosis].", "content": "In 124 patients with different forms of chronic neurotoxoplasmosis there was an increased tone of brain vessels without signs of a drop in the pulse blood repletion in the arteries of carotid and vertebro-basillar basins. There was also a decrease of the pulse blood repletion in the extremities (mainly in the lower) with a normal or insigficant increase of the tone in the vascular wall. A normalization of the rheographic curves in pharmacological tests and during treatment indicate a functional character of these changes in most of the cases.", "contents": "[State of the cerebral and peripheral blood circulation in chronic neurotoxoplasmosis]. In 124 patients with different forms of chronic neurotoxoplasmosis there was an increased tone of brain vessels without signs of a drop in the pulse blood repletion in the arteries of carotid and vertebro-basillar basins. There was also a decrease of the pulse blood repletion in the extremities (mainly in the lower) with a normal or insigficant increase of the tone in the vascular wall. A normalization of the rheographic curves in pharmacological tests and during treatment indicate a functional character of these changes in most of the cases."} {"id": "PMID:170758", "title": "[Destruction of cartilage in the adjuvants disease of the rat].", "content": "The structure of cartilage in rats with adjuvant disease was investigated lightmicroscopically and by scanning electron microscopy. Severe destruction of the cartilage with formation of lacunae only was observed in areas previously covered by pannus. However, outside the pannus differences between normal animals and animals with arthritis also were observed. In adjuvant treated animals a more fibrillar structure of the surface was seen as compared with untreated rats. This more fibrillar structure may be due to a loss of mucopolysaccharides. The severe destruction of cartilage must be related to the action of collagenase which only acts in areas with a close contact between cartilage and pannus.", "contents": "[Destruction of cartilage in the adjuvants disease of the rat]. The structure of cartilage in rats with adjuvant disease was investigated lightmicroscopically and by scanning electron microscopy. Severe destruction of the cartilage with formation of lacunae only was observed in areas previously covered by pannus. However, outside the pannus differences between normal animals and animals with arthritis also were observed. In adjuvant treated animals a more fibrillar structure of the surface was seen as compared with untreated rats. This more fibrillar structure may be due to a loss of mucopolysaccharides. The severe destruction of cartilage must be related to the action of collagenase which only acts in areas with a close contact between cartilage and pannus."} {"id": "PMID:170764", "title": "Isolation, purification and properties of a factor from rheumatoid synovial fluid activating the latent forms of collagenolytic enzymes.", "content": "1. An activator catalysing specifically conversion of latent forms of human leucocyte collagenase and gelatin-specific protease into the active forms, has been isolated from rheumatoid synovial fluid and purified 55-fold with a yield of 16%. 2. Molecular weight of the activator is about 35 000. 3. The activator is thermolabile, and is irreversibly inactivated at pH below 5.5 or in the presence of low concentrations of trypsin or papain; it is resistant to the action of lysozyme, hyaluronidase, diisopropylfluorophosphate, soybean trypsin inhibitor, p-chloromercuribenzoate, iodoacetamide and dithiothreitol. 4. The activator did not show any activity towards collagen, gelatin, casein, haemoglobin, histones, elastin or p-phenylazobenzyloxycarbonyl-peptide.", "contents": "Isolation, purification and properties of a factor from rheumatoid synovial fluid activating the latent forms of collagenolytic enzymes. 1. An activator catalysing specifically conversion of latent forms of human leucocyte collagenase and gelatin-specific protease into the active forms, has been isolated from rheumatoid synovial fluid and purified 55-fold with a yield of 16%. 2. Molecular weight of the activator is about 35 000. 3. The activator is thermolabile, and is irreversibly inactivated at pH below 5.5 or in the presence of low concentrations of trypsin or papain; it is resistant to the action of lysozyme, hyaluronidase, diisopropylfluorophosphate, soybean trypsin inhibitor, p-chloromercuribenzoate, iodoacetamide and dithiothreitol. 4. The activator did not show any activity towards collagen, gelatin, casein, haemoglobin, histones, elastin or p-phenylazobenzyloxycarbonyl-peptide."} {"id": "PMID:170765", "title": "Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver.", "content": "Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products.", "contents": "Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver. Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products."} {"id": "PMID:170766", "title": "Spontaneous rupture of the liver.", "content": "Four cases of spontaneous rupture of the liver are reported. In all these cases, pathological processes in the liver caused the rupture, i.e. primary hepatoma in 3 cases and a benign angiomatous tumour in one case. In one case, the diagnosis was not established until autopsy and in 3 cases at operation. In one of these latter cases, however, the bleeding source was not found until at a secondary surgical exploration. In none of the patients was the diagnosis suspected preoperatively. Four-quadrant puncture is highly recommended even in patients with only a slight suspicion of intra-abdominal hemorrhage. In cases with a ruptured solitary primary liver tumour, an acute liver resection might be performed. If there are multiple tumours--primary or secondary--simple hemostasis seems to be the treatment of choice. In patients with intra-abdominal hemorrhage, thorough palpation of the whole liver is an obligatory manovre during surgery.", "contents": "Spontaneous rupture of the liver. Four cases of spontaneous rupture of the liver are reported. In all these cases, pathological processes in the liver caused the rupture, i.e. primary hepatoma in 3 cases and a benign angiomatous tumour in one case. In one case, the diagnosis was not established until autopsy and in 3 cases at operation. In one of these latter cases, however, the bleeding source was not found until at a secondary surgical exploration. In none of the patients was the diagnosis suspected preoperatively. Four-quadrant puncture is highly recommended even in patients with only a slight suspicion of intra-abdominal hemorrhage. In cases with a ruptured solitary primary liver tumour, an acute liver resection might be performed. If there are multiple tumours--primary or secondary--simple hemostasis seems to be the treatment of choice. In patients with intra-abdominal hemorrhage, thorough palpation of the whole liver is an obligatory manovre during surgery."} {"id": "PMID:170770", "title": "Adrenal mediation of the effect of excess ACTH on testosterone levels in male: a study of a patient with probable ACTH secreting medullary thyroid carcinoma.", "content": "An adult male patient with probable ectopic ACTH production by a medullary carcinoma of the thyroid, was studied before and after bilateral adrenalectomy. Pre-operatively, the patient had low plasma testosterone levels that returned to normal after surgery. The clinical course and study of the patient showed that, 1) chronic excess of ACTH may lower plasma testosterone levels in man, and 2) that this may be mediated through its effect on the adrenals.", "contents": "Adrenal mediation of the effect of excess ACTH on testosterone levels in male: a study of a patient with probable ACTH secreting medullary thyroid carcinoma. An adult male patient with probable ectopic ACTH production by a medullary carcinoma of the thyroid, was studied before and after bilateral adrenalectomy. Pre-operatively, the patient had low plasma testosterone levels that returned to normal after surgery. The clinical course and study of the patient showed that, 1) chronic excess of ACTH may lower plasma testosterone levels in man, and 2) that this may be mediated through its effect on the adrenals."} {"id": "PMID:170767", "title": "Application of immunofluorescent technique in the cytologic diagnosis of human herpes simplex keratitis.", "content": "In cases of keratitis it is often desirable for a correct treatment that a rapid etiologic diagnosis is established. This can easily be accomplished by using the immunofluorescent tecnique for the demonstration of herpes simplex viral antigen in corneal epithelium cells.", "contents": "Application of immunofluorescent technique in the cytologic diagnosis of human herpes simplex keratitis. In cases of keratitis it is often desirable for a correct treatment that a rapid etiologic diagnosis is established. This can easily be accomplished by using the immunofluorescent tecnique for the demonstration of herpes simplex viral antigen in corneal epithelium cells."} {"id": "PMID:170771", "title": "Oestrogen-inducible uterine progesterone receptors. characteristics in the ovariectomized immature and adult hamster.", "content": "In order to characterize the uterine progesterone-binding proteins of oestrogen-primed and unprimed, ovariectomized immature and adult golden hamsters, cytosols were incubated with [3H]progesterone and/or other steroids and analyzed by sucrose-glycerol density gradient ultracentrifugation. Progesterone-binding components with sedimentation coefficients of 7S and 4.5S were found in the uterine cytosols, but not in the cytosols from the hypothalamus, pituitary, diaphragm, or small intestine. Oestradiol-17beta markedly elevated the level of 7S uterine receptor and this increase appeared to be due to new receptor synthesis, since actinomycin D and cycloheximide blocked this response. Fifty to 100 mug of oestradiol-17beta per kg body weight was found to promote a maximum increase in the 7S macromolecular component. The 7S receptor showed a tendency to saturate at 1 X 10(-7) M [1,2-3H]progesterone, indicating limited capacity. At a molar ratio of 100:1, unlabeled progesterone competed effectively for 7S and 4,5S [3H]progesterone binding, whereas 5alpha-pregnane-3,20-dione, oestradiol-17beta and testosterone did not. Moreover, [1,2-3H]cortisol and [1,2-3H]corticosterone did not bind to the 7S receptor, implying steroid specificity. CI-628, a non-steroid oestrogen antagonist, completely prevented [6,7-3H]oestradiol-17beta binding to its 8.5S uterine cytosol receptor, but was entirely without effect on 7S and 4.5S [3H]progesterone binding. Pronase, but not DNase or RNase, abolished 7S and 4.5S progesterone binding, suggesting that the binders are at least in part protein. Protamine sulphate and p-hydroxymercuribenzoate also obliterated 7S binding, implying that this receptor may be an acidic protein which contains sulfhydryl groups that are necessary for progesterone binding.", "contents": "Oestrogen-inducible uterine progesterone receptors. characteristics in the ovariectomized immature and adult hamster. In order to characterize the uterine progesterone-binding proteins of oestrogen-primed and unprimed, ovariectomized immature and adult golden hamsters, cytosols were incubated with [3H]progesterone and/or other steroids and analyzed by sucrose-glycerol density gradient ultracentrifugation. Progesterone-binding components with sedimentation coefficients of 7S and 4.5S were found in the uterine cytosols, but not in the cytosols from the hypothalamus, pituitary, diaphragm, or small intestine. Oestradiol-17beta markedly elevated the level of 7S uterine receptor and this increase appeared to be due to new receptor synthesis, since actinomycin D and cycloheximide blocked this response. Fifty to 100 mug of oestradiol-17beta per kg body weight was found to promote a maximum increase in the 7S macromolecular component. The 7S receptor showed a tendency to saturate at 1 X 10(-7) M [1,2-3H]progesterone, indicating limited capacity. At a molar ratio of 100:1, unlabeled progesterone competed effectively for 7S and 4,5S [3H]progesterone binding, whereas 5alpha-pregnane-3,20-dione, oestradiol-17beta and testosterone did not. Moreover, [1,2-3H]cortisol and [1,2-3H]corticosterone did not bind to the 7S receptor, implying steroid specificity. CI-628, a non-steroid oestrogen antagonist, completely prevented [6,7-3H]oestradiol-17beta binding to its 8.5S uterine cytosol receptor, but was entirely without effect on 7S and 4.5S [3H]progesterone binding. Pronase, but not DNase or RNase, abolished 7S and 4.5S progesterone binding, suggesting that the binders are at least in part protein. Protamine sulphate and p-hydroxymercuribenzoate also obliterated 7S binding, implying that this receptor may be an acidic protein which contains sulfhydryl groups that are necessary for progesterone binding."} {"id": "PMID:170768", "title": "Exfoliative cytopathologic studies in organ transplantation IV. The cytologic diagnosis of herpesvirus in the urine of renal allograft recipients.", "content": "Cellular changes of herpesvirus infection were found in 12 urine specimens from 4 renal allograft recipients. The cytologic diagnosis of herpes infection in the urine of renal allograft recipients has not been reported previously and is significant because of recent suggestions that viral infection contribute to allograft rejections. We were unable to find a consistent correlation between the cytologic diagnosis of herpesvirus and transplant rejection in the patients we studied.", "contents": "Exfoliative cytopathologic studies in organ transplantation IV. The cytologic diagnosis of herpesvirus in the urine of renal allograft recipients. Cellular changes of herpesvirus infection were found in 12 urine specimens from 4 renal allograft recipients. The cytologic diagnosis of herpes infection in the urine of renal allograft recipients has not been reported previously and is significant because of recent suggestions that viral infection contribute to allograft rejections. We were unable to find a consistent correlation between the cytologic diagnosis of herpesvirus and transplant rejection in the patients we studied."} {"id": "PMID:170772", "title": "An attempt to influence by drugs recovery sleep after sleep deprivation.", "content": "Rats were deprived of sleep by placing them for 36 hours in a slowly moving drum. After this procedure, during recovery sleep, the latency of onset of the first rhombencephalic - paradoxical sleep period decreased and the proportion of telencephalic/rhombencephalic - slow wave sleep reversed (during the first hour of recovery sleep). Repeated administration during the deprivation period of physostigmine (0,5 mg/kg i. p. in 30 min intervals 20-30 times) inducing in waking animals in EEG pattern close to that of rhombencephalic sleep, or atropine (1 mg/kg i. p. in 60 min intervals 10-15 times) evoking an activity resembling telencephalic sleep, did not change the above measures of recovery sleep. Pharmacologically induced sleep-like patterns did not substitute for the sleep the rats were deprived off.", "contents": "An attempt to influence by drugs recovery sleep after sleep deprivation. Rats were deprived of sleep by placing them for 36 hours in a slowly moving drum. After this procedure, during recovery sleep, the latency of onset of the first rhombencephalic - paradoxical sleep period decreased and the proportion of telencephalic/rhombencephalic - slow wave sleep reversed (during the first hour of recovery sleep). Repeated administration during the deprivation period of physostigmine (0,5 mg/kg i. p. in 30 min intervals 20-30 times) inducing in waking animals in EEG pattern close to that of rhombencephalic sleep, or atropine (1 mg/kg i. p. in 60 min intervals 10-15 times) evoking an activity resembling telencephalic sleep, did not change the above measures of recovery sleep. Pharmacologically induced sleep-like patterns did not substitute for the sleep the rats were deprived off."} {"id": "PMID:170769", "title": "Cytopathogenicity of cytomegalovirus to human ecto- and endocervical epithelial cells in vitro.", "content": "The effect of cytomegalovirus on cell cultures initiated from human uterine endo- and ectocervix was studied. Pure epithelial cultures were obtained which differed in morphology depending on the source. The ectocervical cells grew in mosaic-like regular epithelial patterns, whereas endocervical cultures had a poorer intercellular cohesion, irregular polygonal cell form and curved cytoplasmic processes. Occasional fibroblastic colonies grew in three out of 32 ectocervical cultures and in none of the endocervical cultures. In the latter no cells with fibroblast-specific surface antigens could be seen. Ectocervical cells were resistant to cytomegalovirus infection; only in three out of 20 cultures could individual altered cells be detected. In contrast, endocervical cultures supported the growth of cytomegalovirus and at best 30 per cent of the explanted colonies showed cytologic alterations as well as virus-specific immunofluorescence. The various types of altered cells are described and it si concluded that endocervical epithelial cells may be the site of replication of human cytomegalovirus so commonly found in cervical secretions.", "contents": "Cytopathogenicity of cytomegalovirus to human ecto- and endocervical epithelial cells in vitro. The effect of cytomegalovirus on cell cultures initiated from human uterine endo- and ectocervix was studied. Pure epithelial cultures were obtained which differed in morphology depending on the source. The ectocervical cells grew in mosaic-like regular epithelial patterns, whereas endocervical cultures had a poorer intercellular cohesion, irregular polygonal cell form and curved cytoplasmic processes. Occasional fibroblastic colonies grew in three out of 32 ectocervical cultures and in none of the endocervical cultures. In the latter no cells with fibroblast-specific surface antigens could be seen. Ectocervical cells were resistant to cytomegalovirus infection; only in three out of 20 cultures could individual altered cells be detected. In contrast, endocervical cultures supported the growth of cytomegalovirus and at best 30 per cent of the explanted colonies showed cytologic alterations as well as virus-specific immunofluorescence. The various types of altered cells are described and it si concluded that endocervical epithelial cells may be the site of replication of human cytomegalovirus so commonly found in cervical secretions."} {"id": "PMID:170774", "title": "Some new observations in an intracranial germinoma.", "content": "A case of an intracranial germinoma from the suprasellar region of a 9-year-old girl was examined in the electron microscope. The tumor consists, for the most part, of both large polygonal and small lymphocyte-like elements. Annulate lamellae are common in the epithelial cells. The small blood vessels are fenestrated, and the endothelial cells contain tubular bodies, membrane-bounded vacuoles containing dense fluid and occasional tubules, arrays of tubules within the nuclear envelope and rough endoplasmic reticulum, and a markedly irregular luminal surface. Dense, lamellated structures are present in the widened, collagen-containing perivascular spaces.", "contents": "Some new observations in an intracranial germinoma. A case of an intracranial germinoma from the suprasellar region of a 9-year-old girl was examined in the electron microscope. The tumor consists, for the most part, of both large polygonal and small lymphocyte-like elements. Annulate lamellae are common in the epithelial cells. The small blood vessels are fenestrated, and the endothelial cells contain tubular bodies, membrane-bounded vacuoles containing dense fluid and occasional tubules, arrays of tubules within the nuclear envelope and rough endoplasmic reticulum, and a markedly irregular luminal surface. Dense, lamellated structures are present in the widened, collagen-containing perivascular spaces."} {"id": "PMID:170775", "title": "Ultrastructural alterations of tissue cultures from human fetal brain infected with the E variant of EMC virus.", "content": "Explant outgrowths from human fetal brain were infected with 104 plaque forming units of the E variant of the encephalomyocarditis virus. Ultrastructurally, the majority of the cultured cells were astrocytes containing a moderate amount of glial fibrils. The earliest alterations at 44 hrs after infection of the culture consisted of dilatation of the rough endoplasmic reticulum (ER) and moderate enlargement of the mitochondria with increased density of their matrix. Twenty hours thereafter, increased amounts of the rough ER and of free ribosomes were observed in the infected cells. This was followed by aggregates of larger dense particles which developed into a parallel lattice-like pattern within the cytoplasm, presumably presenting viral particles, without obvious cytonecrosis. The present observations of the continuous development of the crystalloid formation of the virus within the cytoplasmic matrix as well as the mode of formation of the free ribosomes adjacent to the ER support the previous hypothesis that, after the uptake of the virus into the cytoplasmic matrix, it associates with the ER, where production of viral RNA polymerase and of viral RNA is initiated.", "contents": "Ultrastructural alterations of tissue cultures from human fetal brain infected with the E variant of EMC virus. Explant outgrowths from human fetal brain were infected with 104 plaque forming units of the E variant of the encephalomyocarditis virus. Ultrastructurally, the majority of the cultured cells were astrocytes containing a moderate amount of glial fibrils. The earliest alterations at 44 hrs after infection of the culture consisted of dilatation of the rough endoplasmic reticulum (ER) and moderate enlargement of the mitochondria with increased density of their matrix. Twenty hours thereafter, increased amounts of the rough ER and of free ribosomes were observed in the infected cells. This was followed by aggregates of larger dense particles which developed into a parallel lattice-like pattern within the cytoplasm, presumably presenting viral particles, without obvious cytonecrosis. The present observations of the continuous development of the crystalloid formation of the virus within the cytoplasmic matrix as well as the mode of formation of the free ribosomes adjacent to the ER support the previous hypothesis that, after the uptake of the virus into the cytoplasmic matrix, it associates with the ER, where production of viral RNA polymerase and of viral RNA is initiated."} {"id": "PMID:170776", "title": "Chick muscle in tissue culture: the ubiquity of viral infection.", "content": "In chick skeletal muscle fibers cultured from embryos of commercially obtained \"normal\" eggs we have demonstrated numerous C-particles and large amounts of avian leucosis/sarcoma envelope antigen, especially when cultured in the presence of dinitrophenol. C-particles were present in t-tubules, which were possible intracellular viaducts of infection or dissemination and perhaps were the loci of receptors of viral invasion of the cytoplasm and sites of egress. The abundant lace-like membraneous proliferations, probably of t-tubules, usually had C-particles adjacent to or within them and perhaps were virus-provoked. Questioned is the validity of using cultured muscle, or extract, of embryos from ordinary chicken eggs for analysing normal biological phenomena--or conversely, is viral influence \"normal\" in chick development?", "contents": "Chick muscle in tissue culture: the ubiquity of viral infection. In chick skeletal muscle fibers cultured from embryos of commercially obtained \"normal\" eggs we have demonstrated numerous C-particles and large amounts of avian leucosis/sarcoma envelope antigen, especially when cultured in the presence of dinitrophenol. C-particles were present in t-tubules, which were possible intracellular viaducts of infection or dissemination and perhaps were the loci of receptors of viral invasion of the cytoplasm and sites of egress. The abundant lace-like membraneous proliferations, probably of t-tubules, usually had C-particles adjacent to or within them and perhaps were virus-provoked. Questioned is the validity of using cultured muscle, or extract, of embryos from ordinary chicken eggs for analysing normal biological phenomena--or conversely, is viral influence \"normal\" in chick development?"} {"id": "PMID:170777", "title": "[Cerebral granular cell tumor in the rat after intraperitoneal application of aflatoxin b1 during pregnancy (author's transl)].", "content": "On a rat, which has spontaneous died 12 months after 4 times i.p. application of aflatoxin during pregnancy, there has been found a frontal tumor barely of the size of a pepper-corn which came out from the leptomeninx. A comparison to the Abrikossoff tumor concerning the light- and electron-microscope as well as the nucleic-acid concentration is justified. The protein content of the granula of the tumor cells is higher than the values known in the granular-cell myoblastoma of man.", "contents": "[Cerebral granular cell tumor in the rat after intraperitoneal application of aflatoxin b1 during pregnancy (author's transl)]. On a rat, which has spontaneous died 12 months after 4 times i.p. application of aflatoxin during pregnancy, there has been found a frontal tumor barely of the size of a pepper-corn which came out from the leptomeninx. A comparison to the Abrikossoff tumor concerning the light- and electron-microscope as well as the nucleic-acid concentration is justified. The protein content of the granula of the tumor cells is higher than the values known in the granular-cell myoblastoma of man."} {"id": "PMID:170778", "title": "Hematogenous cells in experimental Japanese encephalitis.", "content": "Four adult mice were injected with 3H-thymidine repeatedly so that in their brains only circulating blood cells were labelled with 3H-thymidine. They then received an intracerebral injection of Japanese encephalitis virus, were sacrified on the 3rd, 4th and 5th day after inoculation: the brains were examined by light and electron microscopic autoradiography. Inflammatory cells appearing in the brain parenchyma and perivascularly in the acute stage of the experimental Japanese encephalitis are derived from circulating mononuclear leukocytes. They assume the shape of \"rod cells\" and are the main constituents of the \"glial nodule\" in the brain parenchyma. Their fine structural characteristics are discussed.", "contents": "Hematogenous cells in experimental Japanese encephalitis. Four adult mice were injected with 3H-thymidine repeatedly so that in their brains only circulating blood cells were labelled with 3H-thymidine. They then received an intracerebral injection of Japanese encephalitis virus, were sacrified on the 3rd, 4th and 5th day after inoculation: the brains were examined by light and electron microscopic autoradiography. Inflammatory cells appearing in the brain parenchyma and perivascularly in the acute stage of the experimental Japanese encephalitis are derived from circulating mononuclear leukocytes. They assume the shape of \"rod cells\" and are the main constituents of the \"glial nodule\" in the brain parenchyma. Their fine structural characteristics are discussed."} {"id": "PMID:170779", "title": "Vascular and neuroglial changes in experimental herpes simplex encephalitis enzyme histochemical study.", "content": "An enzyme histochemical study of experimental herpes simplex encephalitis of the mouse has revealed a decrease in the number of capillaries displaying alkaline phosphatase activity. Glial cells showed increased Inosine 5 diphosphatase and ATPase activity. These enzyme histochemical changes were distributed throughout the nervous parenchyma while the lesions, seen by light microscopy, are localized to well defined areas. Mice inoculated with a pure culture of irradiated HSV failed to show the above mentioned modifications.", "contents": "Vascular and neuroglial changes in experimental herpes simplex encephalitis enzyme histochemical study. An enzyme histochemical study of experimental herpes simplex encephalitis of the mouse has revealed a decrease in the number of capillaries displaying alkaline phosphatase activity. Glial cells showed increased Inosine 5 diphosphatase and ATPase activity. These enzyme histochemical changes were distributed throughout the nervous parenchyma while the lesions, seen by light microscopy, are localized to well defined areas. Mice inoculated with a pure culture of irradiated HSV failed to show the above mentioned modifications."} {"id": "PMID:170780", "title": "Fine structure of intercellular junctions and blood vessels in medulloblastomas.", "content": "Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endothelia contain frequent tubular bodies and other inclusions which may be related to them.", "contents": "Fine structure of intercellular junctions and blood vessels in medulloblastomas. Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endothelia contain frequent tubular bodies and other inclusions which may be related to them."} {"id": "PMID:170781", "title": "Phagocytosis in the choroidal endothelium of the ischaemic rabbit eye.", "content": "Phagosomes containing membranous debris were found in the choroidal endothelium of rabbits following periods of acute pressure ischaemia and also accompanying periods of post-ischaemic recovery. The membranous debris may be of visual cell origin and pass into the choroid by a transpigment epithelial route. Ischaemia may be a sufficient stimulus to induce the vascular endothelium to engulf this material. The phagosomes were found only in ischaemic or post-ischaemic tissue.", "contents": "Phagocytosis in the choroidal endothelium of the ischaemic rabbit eye. Phagosomes containing membranous debris were found in the choroidal endothelium of rabbits following periods of acute pressure ischaemia and also accompanying periods of post-ischaemic recovery. The membranous debris may be of visual cell origin and pass into the choroid by a transpigment epithelial route. Ischaemia may be a sufficient stimulus to induce the vascular endothelium to engulf this material. The phagosomes were found only in ischaemic or post-ischaemic tissue."} {"id": "PMID:170782", "title": "Development of osteopenia in the fourth lumbar vertebra during prolonged bed rest after operation for scoliosis.", "content": "The fourth lumbar vertebra was studied with dual photon absorptiometry in a group of young women immobilized in bed for 21 to 46 days after operation for scoliosis. Twelve out of 13 showed loss of bone content. The monthly loss in most patients highly exceeded earlier reported losses from other bones and significantly exceeded the methodological error.", "contents": "Development of osteopenia in the fourth lumbar vertebra during prolonged bed rest after operation for scoliosis. The fourth lumbar vertebra was studied with dual photon absorptiometry in a group of young women immobilized in bed for 21 to 46 days after operation for scoliosis. Twelve out of 13 showed loss of bone content. The monthly loss in most patients highly exceeded earlier reported losses from other bones and significantly exceeded the methodological error."} {"id": "PMID:170784", "title": "Mechanism of the formation of megamitochondria induced by copper-chelating agents. III. Formation and some biochemical properties of megamitochondria induced by diethyldithiocarbamate (DDC).", "content": "Sodium diethyldithiocarbamate (DDC), a copper-chelating agent, has induced megamitochondria in mouse hepatocytes simply by feeding the animal with a diet containing the noxious agent. Megamitochondria have been isolated from the liver, specified above, in a medium containing albumin. Phosphorylating capacities of such megamitochondria have revealed that they are tightly coupled. Biochemical properties of megamitochondria, such as cytochrome contents, activities of copper-containing enzymes. and contents of Cu2+, strongly suggest that copper-chelating action of the agent may not be related to the formation of megamitochondria just as in the case of cuprizone-induced megamitochondria. Moreover, contents of divalent metals such as Ca2+ and Mg2+ were drastically decreased in the mitochondrial preparation specified above. Similarities in biochemical aspects of DDC-induced megamitochondria to those of cuprizone-induced megamitochondria together with ultrastructural changes in the liver and clinical appearances of the mouse treated with the agent would strongly suggest that the mechanism of the formation of megamitochondria induced either by DDC or by cuprizone may be the same.", "contents": "Mechanism of the formation of megamitochondria induced by copper-chelating agents. III. Formation and some biochemical properties of megamitochondria induced by diethyldithiocarbamate (DDC). Sodium diethyldithiocarbamate (DDC), a copper-chelating agent, has induced megamitochondria in mouse hepatocytes simply by feeding the animal with a diet containing the noxious agent. Megamitochondria have been isolated from the liver, specified above, in a medium containing albumin. Phosphorylating capacities of such megamitochondria have revealed that they are tightly coupled. Biochemical properties of megamitochondria, such as cytochrome contents, activities of copper-containing enzymes. and contents of Cu2+, strongly suggest that copper-chelating action of the agent may not be related to the formation of megamitochondria just as in the case of cuprizone-induced megamitochondria. Moreover, contents of divalent metals such as Ca2+ and Mg2+ were drastically decreased in the mitochondrial preparation specified above. Similarities in biochemical aspects of DDC-induced megamitochondria to those of cuprizone-induced megamitochondria together with ultrastructural changes in the liver and clinical appearances of the mouse treated with the agent would strongly suggest that the mechanism of the formation of megamitochondria induced either by DDC or by cuprizone may be the same."} {"id": "PMID:170785", "title": "The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer.", "content": "Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa.", "contents": "The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer. Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa."} {"id": "PMID:170786", "title": "The formation of enlarged and giant mitochondria in the aging process of human hepatic cells.", "content": "Measurement of area, circumference and total length of membrane profile of mitochondria of hepatic cells in 61 human biopsy materials (age range 21 to 81 years) have been ultramicrometrically performed on electron micrographs, supplemented by electroncytochemical examination of cytochrome c oxidase activity in some cases. The mitochondria decreased in number after 60 years of age. The first stage of compensation for the numerical loss of mitochondria was achieved by an increase of cristae in each mitochondrion, followed with a five year lag by an increase in their size. Formation of enlarged and giant mitochondria in aging process following the significant decrease in their number, may be considered to be of similar mechanism to polyploidization of the nucleus, whose division is interfered.", "contents": "The formation of enlarged and giant mitochondria in the aging process of human hepatic cells. Measurement of area, circumference and total length of membrane profile of mitochondria of hepatic cells in 61 human biopsy materials (age range 21 to 81 years) have been ultramicrometrically performed on electron micrographs, supplemented by electroncytochemical examination of cytochrome c oxidase activity in some cases. The mitochondria decreased in number after 60 years of age. The first stage of compensation for the numerical loss of mitochondria was achieved by an increase of cristae in each mitochondrion, followed with a five year lag by an increase in their size. Formation of enlarged and giant mitochondria in aging process following the significant decrease in their number, may be considered to be of similar mechanism to polyploidization of the nucleus, whose division is interfered."} {"id": "PMID:170783", "title": "Damage to the stria vascularis in the guinea pig by acute atoxyl intoxication.", "content": "The aim of the present study was to show the morphological degeneration at the ultrastructural level, after damaging the stria vascularis experimentally. The acute lesions, after acute atoxyl intoxication, occur after about 12 hours, and begin as a degeneration of both the marginal and the intermediate cells, whereas the basal cells remain mainly unaffected. The severely damaged marginal or intermediate cells may become loosened from the stria vascularis and rejected from it into the endolymphatic space. Under such conditions the basal cells may line the surface facing the endolymph, although this occurs very rarely. Intially, there may be a slight bulging of Reissner's membrane, but soon the membrane becomes depressed, and sometimes a total collapse occurs, with Reissner's membrane flattened over the tectorial membrane against the organ of Corti. It is only seldom that Reissner's membrane touches the strial surface. Mitochondrial degeneration with formation of intramitochondrial inclusion bodies is an interesting early finding in the damage pattern.", "contents": "Damage to the stria vascularis in the guinea pig by acute atoxyl intoxication. The aim of the present study was to show the morphological degeneration at the ultrastructural level, after damaging the stria vascularis experimentally. The acute lesions, after acute atoxyl intoxication, occur after about 12 hours, and begin as a degeneration of both the marginal and the intermediate cells, whereas the basal cells remain mainly unaffected. The severely damaged marginal or intermediate cells may become loosened from the stria vascularis and rejected from it into the endolymphatic space. Under such conditions the basal cells may line the surface facing the endolymph, although this occurs very rarely. Intially, there may be a slight bulging of Reissner's membrane, but soon the membrane becomes depressed, and sometimes a total collapse occurs, with Reissner's membrane flattened over the tectorial membrane against the organ of Corti. It is only seldom that Reissner's membrane touches the strial surface. Mitochondrial degeneration with formation of intramitochondrial inclusion bodies is an interesting early finding in the damage pattern."} {"id": "PMID:170787", "title": "Induction of metastasizing carcinoma in rats and their biological characteristics.", "content": "Induction of a spontaneously metastasizing carcinoma in rats was attempted. Four-week-old Sprague-Dawley female rats were thymectomized or/and splenectomized and fed 200 mg (20 mg times 10) of 3-methylcholanthrene from 7 weeks of age. In addition to these treatments, the early-appearing tumors were excised in order to select by isoimmunity the late-appearing ones that were less antigenic. The latter were easily transplanted into normal syngeneic female rats with metastasis to remote organs. This metastasizing capacity of the tumor became an inherent character in syngeneic normal rats from generation to generation of transplantation. With one of these tumors (MRMT-1) many cancer cells were histologically detected in circulating blood 3 days after tumor transplantation and arrested in capillary beds of lungs. The spontaneous metastasis to lymph nodes and lungs was macroscopically found within several weeks after tumor transplantation.", "contents": "Induction of metastasizing carcinoma in rats and their biological characteristics. Induction of a spontaneously metastasizing carcinoma in rats was attempted. Four-week-old Sprague-Dawley female rats were thymectomized or/and splenectomized and fed 200 mg (20 mg times 10) of 3-methylcholanthrene from 7 weeks of age. In addition to these treatments, the early-appearing tumors were excised in order to select by isoimmunity the late-appearing ones that were less antigenic. The latter were easily transplanted into normal syngeneic female rats with metastasis to remote organs. This metastasizing capacity of the tumor became an inherent character in syngeneic normal rats from generation to generation of transplantation. With one of these tumors (MRMT-1) many cancer cells were histologically detected in circulating blood 3 days after tumor transplantation and arrested in capillary beds of lungs. The spontaneous metastasis to lymph nodes and lungs was macroscopically found within several weeks after tumor transplantation."} {"id": "PMID:170788", "title": "Time course of changes in plasma renin after blockade of the renin-system. Studies of conscious and anaesthetized, normal, adrenalectomized and spontaneously hypertensive rats.", "content": "Inhibition of the angiotensin I converting enzyme with SQ 20.881 results in a 2 to 35 fold increase in plasma renin concentration in normal rats and in spontaneously hypertensive rats. The effect is transient, lasting for 1 to 3 hours even in the presence of prolonged blockade. The relative increase is independent of the pretreatment plasma renin concentration. The blood pressure is unchanged in conscious rats in which the effect of SQ 20.881 on plasma renin is believed to be due to a blockade of the negative feedback of angiotensin II on renin release. In anaesthetized rats, SQ 20.88) has an additional hypotensive effect which augments the increase in plasma renin. Saralasin is without effect on blood pressure and plasma renin in conscious normal rats and in spontaneously hypertensive rats, while it causes a transient 3 to 27 fold increase in plasma renin concentration in anaesthetized rats. It is suggested that this increase is hardly due to an interception of the feedback, but to the concomitant fall in blood pressure, as a similar hypotension and increase in plasma renin is produced by dihydralazine. It is furthermore found that Saralasin blocks renin release induced by SQ 20.881. This demonstrates that Saralasin is bound to the receptors in the juxtaglomerular cells and has slight, agonistic properties there. Both in conscious rats and in anaesthetized adrenalectomized rats substituted with DOCA and salt, SQ 20.881 as well Saralasin causes transient increases in plasma renin concentration. If such rats are only substituted with salt and not with DOCA, the effects of both blockers are in the form of severe hypotension and a permanent elevation of plasma renin.", "contents": "Time course of changes in plasma renin after blockade of the renin-system. Studies of conscious and anaesthetized, normal, adrenalectomized and spontaneously hypertensive rats. Inhibition of the angiotensin I converting enzyme with SQ 20.881 results in a 2 to 35 fold increase in plasma renin concentration in normal rats and in spontaneously hypertensive rats. The effect is transient, lasting for 1 to 3 hours even in the presence of prolonged blockade. The relative increase is independent of the pretreatment plasma renin concentration. The blood pressure is unchanged in conscious rats in which the effect of SQ 20.881 on plasma renin is believed to be due to a blockade of the negative feedback of angiotensin II on renin release. In anaesthetized rats, SQ 20.88) has an additional hypotensive effect which augments the increase in plasma renin. Saralasin is without effect on blood pressure and plasma renin in conscious normal rats and in spontaneously hypertensive rats, while it causes a transient 3 to 27 fold increase in plasma renin concentration in anaesthetized rats. It is suggested that this increase is hardly due to an interception of the feedback, but to the concomitant fall in blood pressure, as a similar hypotension and increase in plasma renin is produced by dihydralazine. It is furthermore found that Saralasin blocks renin release induced by SQ 20.881. This demonstrates that Saralasin is bound to the receptors in the juxtaglomerular cells and has slight, agonistic properties there. Both in conscious rats and in anaesthetized adrenalectomized rats substituted with DOCA and salt, SQ 20.881 as well Saralasin causes transient increases in plasma renin concentration. If such rats are only substituted with salt and not with DOCA, the effects of both blockers are in the form of severe hypotension and a permanent elevation of plasma renin."} {"id": "PMID:170789", "title": "The possible utilization of nuclear pockets of lymphocytes in the diagnosis of enzootic bovine leucosis.", "content": "A comparative study of the presence of lymphocytosis and nuclear pockets in lymphocytes was carried out using blood samples from animals belonging to herds with bovine enzootic leucosis and from herds free from leucosis. It was found that there was a correlation between the presence of such nuclear projections in a certain percentage of the lymphocytes and a state of lymphocytosis. As this correlation seemed to be independent of the aetiology of the lymphocytosis, it was not considered possible to employ the demonstration of nuclear pockets as a more specific tool in the diagnosis of bovine enzootic leucosis than the lymphocyte counts in themselves.", "contents": "The possible utilization of nuclear pockets of lymphocytes in the diagnosis of enzootic bovine leucosis. A comparative study of the presence of lymphocytosis and nuclear pockets in lymphocytes was carried out using blood samples from animals belonging to herds with bovine enzootic leucosis and from herds free from leucosis. It was found that there was a correlation between the presence of such nuclear projections in a certain percentage of the lymphocytes and a state of lymphocytosis. As this correlation seemed to be independent of the aetiology of the lymphocytosis, it was not considered possible to employ the demonstration of nuclear pockets as a more specific tool in the diagnosis of bovine enzootic leucosis than the lymphocyte counts in themselves."} {"id": "PMID:170790", "title": "Canine mycoplasmas: cultural and biochemical studies of type and reference strains.", "content": "Media and conditions for cultivation of type and reference strains of the mycoplasmas presently known (except M. bovigenitalium, A. laidlawii and Ureaplasma strains) to occur in dogs are described. The colonial morphology, ultrastructure, filterability and absence of reversion confirmed that the strains belong to the order of Mycoplasmatales. All strains were cholesterol dependent and therefore of the family Mycoplasmataceae, genus Mycoplasma. Finally the most useful biochemical characteristics are specified.", "contents": "Canine mycoplasmas: cultural and biochemical studies of type and reference strains. Media and conditions for cultivation of type and reference strains of the mycoplasmas presently known (except M. bovigenitalium, A. laidlawii and Ureaplasma strains) to occur in dogs are described. The colonial morphology, ultrastructure, filterability and absence of reversion confirmed that the strains belong to the order of Mycoplasmatales. All strains were cholesterol dependent and therefore of the family Mycoplasmataceae, genus Mycoplasma. Finally the most useful biochemical characteristics are specified."} {"id": "PMID:170791", "title": "Subtyping of herpes simplex virus.", "content": "A number of different techniques to be used for the subtyping of herpes simplex virus (HSV) strains were studied. The strains were inoculated on chorio-allantoic membranes of embryonated eggs and on green monkey kidney (GMK) cells in order that the morphology of plaques produced might be observed. They were classified serologically by determination of K-values and inoculated intracerebrally in mice in order that their pathogenicity for mice might be observed. The inhibitory effect of high concentrations of thymidine on the multiplication of the strains in GMK cells cultures and the heat-stability of the virus-induced thymidine kinases were investigated. Rates of inactivation of the strains in the presence of AgNO3 were compared and, finally, the association of focal liver necrosis in intraperitoneally inoculated mice with the results of the serological typing was observed. The results suggested that the liver necrosis test was simple as well as accurate and useful as a screening typing-test. Reliable results were also obtained serologically and by the method demonstrating differences in the heat-stability of viral thymidine kinase. Using the other methods studied, difficulties to obtain clear-cut or reproducible typing results were encountered.", "contents": "Subtyping of herpes simplex virus. A number of different techniques to be used for the subtyping of herpes simplex virus (HSV) strains were studied. The strains were inoculated on chorio-allantoic membranes of embryonated eggs and on green monkey kidney (GMK) cells in order that the morphology of plaques produced might be observed. They were classified serologically by determination of K-values and inoculated intracerebrally in mice in order that their pathogenicity for mice might be observed. The inhibitory effect of high concentrations of thymidine on the multiplication of the strains in GMK cells cultures and the heat-stability of the virus-induced thymidine kinases were investigated. Rates of inactivation of the strains in the presence of AgNO3 were compared and, finally, the association of focal liver necrosis in intraperitoneally inoculated mice with the results of the serological typing was observed. The results suggested that the liver necrosis test was simple as well as accurate and useful as a screening typing-test. Reliable results were also obtained serologically and by the method demonstrating differences in the heat-stability of viral thymidine kinase. Using the other methods studied, difficulties to obtain clear-cut or reproducible typing results were encountered."} {"id": "PMID:170792", "title": "Enzyme activities and muscle strength after \"sprint training\" in man.", "content": "Sprint type strength training was performed 3-4 times a week for 8 weeks by 4 healthy male students (16-18 yrs). The training was carried out on a treadmill at high speed and with high inclination. Muscle biopsies were obtained from vastus lateralis before and after the training period for histochemical classification of slow and fast twitch muscle fibres and for biochemical determination of metabolites and enzyme activities. Muscle fibre type distribution was unchanged, whereas fibre area indicated an increase for both fibre types in 3 subjects after training. The muscle enzyme activities of Mg2+ stimulated ATPase, myokinase and creatine phosphokinase increased 30, 20, and 36 percent, respectively. Muscle concentration of ATP and creatine phosphate (CP) did not change with training. Sargent's jump increased with on average 4 cm (from 47 to 51 cm), maximal voluntary contraction (MVC) with 19 kp (from 165 to 184 kp), and endurance at 50 percent of MVC with 9 s (from 47 to 56 s), respectively. After training all subjects showed a gain in body weight (mean 1.4 kg) and in thigh circumference (mean 1.5 cm) indicating a larger leg muscle volume and consequently also an increase in total ATP and CP.", "contents": "Enzyme activities and muscle strength after \"sprint training\" in man. Sprint type strength training was performed 3-4 times a week for 8 weeks by 4 healthy male students (16-18 yrs). The training was carried out on a treadmill at high speed and with high inclination. Muscle biopsies were obtained from vastus lateralis before and after the training period for histochemical classification of slow and fast twitch muscle fibres and for biochemical determination of metabolites and enzyme activities. Muscle fibre type distribution was unchanged, whereas fibre area indicated an increase for both fibre types in 3 subjects after training. The muscle enzyme activities of Mg2+ stimulated ATPase, myokinase and creatine phosphokinase increased 30, 20, and 36 percent, respectively. Muscle concentration of ATP and creatine phosphate (CP) did not change with training. Sargent's jump increased with on average 4 cm (from 47 to 51 cm), maximal voluntary contraction (MVC) with 19 kp (from 165 to 184 kp), and endurance at 50 percent of MVC with 9 s (from 47 to 56 s), respectively. After training all subjects showed a gain in body weight (mean 1.4 kg) and in thigh circumference (mean 1.5 cm) indicating a larger leg muscle volume and consequently also an increase in total ATP and CP."} {"id": "PMID:170793", "title": "Characterization of the metabolism of exogenous cyclic AMP by perfused rat heart and incubated prepubertal rat ovary.", "content": "In order to study the metabolism of extracellular 3',5'-adenosine monophosphate (cAMP), rat hearts were perfused and prepubertal rat ovaries incubated with 3H- and 32P-labelled cAMP (0.025-1 muM). The rate of disappearance of cAMP from the medium was determined by \"Ba-Zn-precipitation\" and degradation products of 3H- and 32P-CAMP by paper chromatography. Both tissues degraded cAMP to 5'-adenosine monophosphate (AMP), but the enzyme kinetic for this phosphodiesterase activity was different (apparent Km value for the heart 3.95 muM and for the ovary 0.2 muM). AMP was further degraded, since also other labelled substances were found in the medium. An uptake of both 3H- and 32P-labelled substance(s) into the heart and the ovary was noticed. Tissue extracts contained several labelled purines, but the amounts of labelled cAMP did not exceed expected amounts in the extracellular space. In the ovary the uptake of cAMP and AMP seemed to be low, since the uptake of labelled substances was inhibited by high concentrations of unlabelled AMP or adenosine. The degradation of 32P-cAMP was unchanged when AMP was present, strongly suggesting that the phosphodiesterase enzyme was acting extracellularly. In the heart added AMP was very rapidly degraded making it impossible to elucidate whether cAMP was degraded extracellularly or not. It is concluded that elimination of extracellular cAMP under physiological conditions can be due to degradation of cAMP by various tissues. At least for the ovary this phosphodiesterase enzyme is extracellularly active.", "contents": "Characterization of the metabolism of exogenous cyclic AMP by perfused rat heart and incubated prepubertal rat ovary. In order to study the metabolism of extracellular 3',5'-adenosine monophosphate (cAMP), rat hearts were perfused and prepubertal rat ovaries incubated with 3H- and 32P-labelled cAMP (0.025-1 muM). The rate of disappearance of cAMP from the medium was determined by \"Ba-Zn-precipitation\" and degradation products of 3H- and 32P-CAMP by paper chromatography. Both tissues degraded cAMP to 5'-adenosine monophosphate (AMP), but the enzyme kinetic for this phosphodiesterase activity was different (apparent Km value for the heart 3.95 muM and for the ovary 0.2 muM). AMP was further degraded, since also other labelled substances were found in the medium. An uptake of both 3H- and 32P-labelled substance(s) into the heart and the ovary was noticed. Tissue extracts contained several labelled purines, but the amounts of labelled cAMP did not exceed expected amounts in the extracellular space. In the ovary the uptake of cAMP and AMP seemed to be low, since the uptake of labelled substances was inhibited by high concentrations of unlabelled AMP or adenosine. The degradation of 32P-cAMP was unchanged when AMP was present, strongly suggesting that the phosphodiesterase enzyme was acting extracellularly. In the heart added AMP was very rapidly degraded making it impossible to elucidate whether cAMP was degraded extracellularly or not. It is concluded that elimination of extracellular cAMP under physiological conditions can be due to degradation of cAMP by various tissues. At least for the ovary this phosphodiesterase enzyme is extracellularly active."} {"id": "PMID:170794", "title": "Imitation of glucagon effects on splanchnic hemodynamics and liver function by N6,2'-O-dibutyryl 3',5'-cyclic AMP (DBcAMP) in cats.", "content": "Fasting cats anesthetized with chloralose were used for the experiments. DBcAMP infused at a rate of 340 nmol/kg/min increased the gastrointestinal and intrahepatic portal conductances whereas the hepatic arterial conductance was decreased. The hemodynamic responses to portal and systemic venous administration of DBcAMP were identical. In half of the experiments DBcAMP increased the splanchnic ethanol elimination rate and oxygen consumption and in all experiments there was a decrease in the plasma clearance and extraction ratio of Indocyanine Green. No change in bile flow was observed. DBcAMP infused at a rate of 85 nmol/kg/min was without significant effects on either splanchnic hemodynamics or liver metabolism. DBcAMP infused at a rate of 850 nmol/kg/min accentuated the decrease in hepatic arterial conductanc- but was found to decrease the splanchnic ethanol elimination rate and oxygen cownsumption. Infusion of cAMP, AMP and adenosine at a rate of 340 nmol/kg/min were without measurable effects. Based on these results it is concluded that like the metabolic effects also the vascular effects of glucagon are caused by stimulation of specific glucagon receptors which results in an intracellular release of cAMP.", "contents": "Imitation of glucagon effects on splanchnic hemodynamics and liver function by N6,2'-O-dibutyryl 3',5'-cyclic AMP (DBcAMP) in cats. Fasting cats anesthetized with chloralose were used for the experiments. DBcAMP infused at a rate of 340 nmol/kg/min increased the gastrointestinal and intrahepatic portal conductances whereas the hepatic arterial conductance was decreased. The hemodynamic responses to portal and systemic venous administration of DBcAMP were identical. In half of the experiments DBcAMP increased the splanchnic ethanol elimination rate and oxygen consumption and in all experiments there was a decrease in the plasma clearance and extraction ratio of Indocyanine Green. No change in bile flow was observed. DBcAMP infused at a rate of 85 nmol/kg/min was without significant effects on either splanchnic hemodynamics or liver metabolism. DBcAMP infused at a rate of 850 nmol/kg/min accentuated the decrease in hepatic arterial conductanc- but was found to decrease the splanchnic ethanol elimination rate and oxygen cownsumption. Infusion of cAMP, AMP and adenosine at a rate of 340 nmol/kg/min were without measurable effects. Based on these results it is concluded that like the metabolic effects also the vascular effects of glucagon are caused by stimulation of specific glucagon receptors which results in an intracellular release of cAMP."} {"id": "PMID:170795", "title": "Rat liver mitochondrial enzyme activities in hypoxia.", "content": "Rat liver mitochondrial enzyme activities were measured after exposing the animals to the atmospheric pressure of 380 mm Hg for 5 h and 14 days. Succinate dehydrogenase and succinate oxidase activities increased significantly during the hypoxic period of 14 days. No change was observed in cytochrome oxidase activity. Malate dehydrogenase and glutamate dehydrogenase activities increased somewhat, but not significantly. The efficiency of oxidative phosphorylation (the ADP:O ratio) in the isolated mitochondria remained unchanged. The exact mitochondrial protein values showed a 15% decrease as compared with the control group. The concentrations of cytochromes did not change significantly in the hypoxic group. During the short hypoxic period succinate dehydrogenase, succinate oxidase and cytochrome oxidase activities increased as compared with those in the control group.", "contents": "Rat liver mitochondrial enzyme activities in hypoxia. Rat liver mitochondrial enzyme activities were measured after exposing the animals to the atmospheric pressure of 380 mm Hg for 5 h and 14 days. Succinate dehydrogenase and succinate oxidase activities increased significantly during the hypoxic period of 14 days. No change was observed in cytochrome oxidase activity. Malate dehydrogenase and glutamate dehydrogenase activities increased somewhat, but not significantly. The efficiency of oxidative phosphorylation (the ADP:O ratio) in the isolated mitochondria remained unchanged. The exact mitochondrial protein values showed a 15% decrease as compared with the control group. The concentrations of cytochromes did not change significantly in the hypoxic group. During the short hypoxic period succinate dehydrogenase, succinate oxidase and cytochrome oxidase activities increased as compared with those in the control group."} {"id": "PMID:170797", "title": "Studies in asymptomatic primary hyperlipidaemia. V. Peripheral circulation.", "content": "The occurrence of early signs of peripheral vascular disease (PVD) of the lower limbs has been studied with digital pulse plethysmography in 160 men and 123 women above the age of 35, who were all subjectively healthy but were found to have primary hyperlipoproteinaemia (HLP) at a health control centre. Quantitative analysis of serum lipoproteins with cholesterol and triglyceride (TG) determination of each of the very low (VLDL), low (LDL) and high (HDL) density lipoprotein clases together with lipoprotein paper electrophoresis was performed. Identical investigations were performed on control subjects with non-elevated serum lipids. Inclination time (IT) was substantially prolonged in 12% of HLP males and 7% of HLP females. The frequency of male subjects with prolonged IT was lower when only LDL was elevated (type IIA) than in the other types of HLP. The subjects with prolonged IT had three characteristic features. 1) Moderate elevations of both serum cholesterol and TG. These elevations occurred often in both VLDL and LDL lipoprotein classes. IT prolongations were not seen when VLDL or LDL lipoproteins were singly maredly elevated. 2) High frequency of smokers. 3) Most of the subjects were above the age of 50. The results suggest that the most atherogenic lipoprotein abnormalities to the arteries of the lower limb are on the one hand the relatively TG-rich part of the LDL (LDL1) fraction and on the other hand the relatively cholesterol-rich part of the VLDL fraction. Furthermore the results stress the deleterious influence of smoking even in the preclinical stage of PVD.", "contents": "Studies in asymptomatic primary hyperlipidaemia. V. Peripheral circulation. The occurrence of early signs of peripheral vascular disease (PVD) of the lower limbs has been studied with digital pulse plethysmography in 160 men and 123 women above the age of 35, who were all subjectively healthy but were found to have primary hyperlipoproteinaemia (HLP) at a health control centre. Quantitative analysis of serum lipoproteins with cholesterol and triglyceride (TG) determination of each of the very low (VLDL), low (LDL) and high (HDL) density lipoprotein clases together with lipoprotein paper electrophoresis was performed. Identical investigations were performed on control subjects with non-elevated serum lipids. Inclination time (IT) was substantially prolonged in 12% of HLP males and 7% of HLP females. The frequency of male subjects with prolonged IT was lower when only LDL was elevated (type IIA) than in the other types of HLP. The subjects with prolonged IT had three characteristic features. 1) Moderate elevations of both serum cholesterol and TG. These elevations occurred often in both VLDL and LDL lipoprotein classes. IT prolongations were not seen when VLDL or LDL lipoproteins were singly maredly elevated. 2) High frequency of smokers. 3) Most of the subjects were above the age of 50. The results suggest that the most atherogenic lipoprotein abnormalities to the arteries of the lower limb are on the one hand the relatively TG-rich part of the LDL (LDL1) fraction and on the other hand the relatively cholesterol-rich part of the VLDL fraction. Furthermore the results stress the deleterious influence of smoking even in the preclinical stage of PVD."} {"id": "PMID:170798", "title": "Studies on the serum lipid and lipoproteins in steatosis of the liver.", "content": "In a medical department, specialized in liver diseases, 45 patients (33 men and 12 women) suffering from steatosis of the liver have been examined with reference to serum lipid abnormalities. Twenty-eight of the patients were chronic alcoholics. Annual check-ups, including biopsy of the liver, were made to evaluate the development of the steatosis. The patients did not receive treatment with drugs or diet. Thirteen patients showed hypercholesterolemia, 16 increased serum triglyceride and 8 increased serum phosphorus lipid. Two showed a type I lipoprotein anomaly and 33 a type II-like pattern, defined as increased beta-lipoprotein associated with increase of serum cholesterol, was found in four cases. Three had a type III and three a type IV abnormal pattern, with increased pre-beta-lipoprotein and serum triglyceride levels. Correlation analysis revealed correlations between pre-beta-lipoprotein and serum triglyceride as well as between serum triglyceride and serum free fatty acid levels.", "contents": "Studies on the serum lipid and lipoproteins in steatosis of the liver. In a medical department, specialized in liver diseases, 45 patients (33 men and 12 women) suffering from steatosis of the liver have been examined with reference to serum lipid abnormalities. Twenty-eight of the patients were chronic alcoholics. Annual check-ups, including biopsy of the liver, were made to evaluate the development of the steatosis. The patients did not receive treatment with drugs or diet. Thirteen patients showed hypercholesterolemia, 16 increased serum triglyceride and 8 increased serum phosphorus lipid. Two showed a type I lipoprotein anomaly and 33 a type II-like pattern, defined as increased beta-lipoprotein associated with increase of serum cholesterol, was found in four cases. Three had a type III and three a type IV abnormal pattern, with increased pre-beta-lipoprotein and serum triglyceride levels. Correlation analysis revealed correlations between pre-beta-lipoprotein and serum triglyceride as well as between serum triglyceride and serum free fatty acid levels."} {"id": "PMID:170799", "title": "Studies in asymptomatic primary hyperlipidaemia. I. Types of hyperlipoproteinaemias and serum lipoprotein concentrations, compositions and interrelations.", "content": "1. In order to study lipoprotein (LP) abnormalities in asymptomatic subjects with hyperlipidaemia, serum cholesterol and triglycerides (TG) were determined in about 20 000 active professional men and women attending a health control linked to their employment. 2. Quantitative LP analysis with preparative ultracentrifugation, separating very low (VLDL), low (LDL) and high (HDL) density LP was subsequently performed on the sera of 314 asymptomatic subjects, who at the screening had serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.5 mmol/l. Cholesterol and TG concentrations were serum and on the top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was based on the concentration of VLDL TG and LDL cholesterol and in addition, in the case of type III and V HLP, the presence of a \"floating beta\" LP and fasting chylomicronaemia, respectively. 3. To illustrate the lipid values in the screened total population distributions of serum cholesterol and TG are given in the age range 41-45 years. In this age range mean serum cholesterol in fasting/non-fasting state was 239+/-2/238+/-1 mg/100 ml in males and 232+/-2/239+/-2 mg/100 ml in females.", "contents": "Studies in asymptomatic primary hyperlipidaemia. I. Types of hyperlipoproteinaemias and serum lipoprotein concentrations, compositions and interrelations. 1. In order to study lipoprotein (LP) abnormalities in asymptomatic subjects with hyperlipidaemia, serum cholesterol and triglycerides (TG) were determined in about 20 000 active professional men and women attending a health control linked to their employment. 2. Quantitative LP analysis with preparative ultracentrifugation, separating very low (VLDL), low (LDL) and high (HDL) density LP was subsequently performed on the sera of 314 asymptomatic subjects, who at the screening had serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.5 mmol/l. Cholesterol and TG concentrations were serum and on the top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was based on the concentration of VLDL TG and LDL cholesterol and in addition, in the case of type III and V HLP, the presence of a \"floating beta\" LP and fasting chylomicronaemia, respectively. 3. To illustrate the lipid values in the screened total population distributions of serum cholesterol and TG are given in the age range 41-45 years. In this age range mean serum cholesterol in fasting/non-fasting state was 239+/-2/238+/-1 mg/100 ml in males and 232+/-2/239+/-2 mg/100 ml in females."} {"id": "PMID:170800", "title": "Studies in asymptomatic primary hyperlipidaemia. Clinical, biochemical and physiological investigations.", "content": "1. To determine lipoprotein (LP) abnormalities, clinical characteristics and preclinical signs of atherosclerosis in asymptomatic subjects with hyperlipidaemia serum cholesterol and triglyceride (TG) concentrations were determined in 20,000 subjects attending a health control centre linked to their employment. 2. Three hundred and fourteen asymptomatic subjects with serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.50 mmol/l in the screening test but without signs or symptoms of secondary hyperlipideaemia or history of cardiovascular disease were examined further. 3. LP analysis with preparative ultracentrifugation separating very lof cholestrol and TG concentrations in each fraction was performed. LP paper electrophoresis was run on while serum and on top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was performed according to WO based upon the values of for VLDL and LDL. Exercise ECG was performed on a heart rate controlled bicycle ergometer. The subjects worked at constant predetermined heart rates. ECG at rest and furing exercise was interpreted without knowledge of whether or not the subject has HLP and coded according to the Minnesota criteria. Digital pulse plethysmography was performed on the lower limbs....", "contents": "Studies in asymptomatic primary hyperlipidaemia. Clinical, biochemical and physiological investigations. 1. To determine lipoprotein (LP) abnormalities, clinical characteristics and preclinical signs of atherosclerosis in asymptomatic subjects with hyperlipidaemia serum cholesterol and triglyceride (TG) concentrations were determined in 20,000 subjects attending a health control centre linked to their employment. 2. Three hundred and fourteen asymptomatic subjects with serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.50 mmol/l in the screening test but without signs or symptoms of secondary hyperlipideaemia or history of cardiovascular disease were examined further. 3. LP analysis with preparative ultracentrifugation separating very lof cholestrol and TG concentrations in each fraction was performed. LP paper electrophoresis was run on while serum and on top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was performed according to WO based upon the values of for VLDL and LDL. Exercise ECG was performed on a heart rate controlled bicycle ergometer. The subjects worked at constant predetermined heart rates. ECG at rest and furing exercise was interpreted without knowledge of whether or not the subject has HLP and coded according to the Minnesota criteria. Digital pulse plethysmography was performed on the lower limbs...."} {"id": "PMID:170796", "title": "Studies in asymptomatic primary hyperlipidaemia. IV. ECG at rest and during exercise and its relation to various lipoprotein classes.", "content": "Among approximately 20,000 apparently healthy subjects whose serum cholesterol and triglyceride (TG) values were screened at a health examination, those with the most pronounced hyperlipidaemia have been selected for further studies. Thus, 188 males and 126 females, aged 30-65 years, with asymptomatic primary hyperlipoproteinaemia (HLP) and 59 male and 69 female controls with non-elevated serum lipids were studied with regard to frequency of ST segment depressions during exercise to near maximal heart rate. Furthermore, the concentrations of cholesterol and TG were determined in the lipoprotein (LP) classes very low (VLDL), low (LDL) and high (HDL) density LP, separated by preparative ultracentrifugation. From the LP analysis each subject's HLP was classified according to the typing system of HLP recommended by the WHO. The frequency of ST depressions (Minnesota code 4.1-4.3 as well as 4.1-4.4) increased with age, was higher in females than in males and was increased in all types of HLP in males. The percentage frequencies of ST depressions 4.1-4.4 in the various types of HLP were (male/female, p against controls): controls 16/36, type IIA 50 (p less than 0.01)/56, type IIB 64 (p less than 0.01)/75 (p less than 0.01)/75 (p less than 0.05), type III 67 (p less than 0.01)/33 and type IV HLP 40 (p less than 0.01/53. There was no significant difference in the frequencies of ST depressions in subjects with \"high\" and \"low\" BP (hypertensives were excluded from the study) or in subjects with \"high\" and \"low\" k-value for the i.v. glucose tolerance. Non-smokers had a tendency to higher frequencies of ST depressions than smokers. The association between different LPs and other \"risk factors\" and the occurrence of ST depressions in HLP were studied further with multiple regression analysis. Invariably age was the best predictor of ST depressions. The LP fraction giving the highest correlation coefficient was LDL cholesterol in both sexes. VLDL TG and LDL TG were also positively and significantly associated with ST depressions. HDL cholesterol was negatively but insignificantly correlated to ST depressions. When age and LDL cholesterol had been entered into the multiple regression, the only factor giving further significance was VLDL TG in males. Probability tables for the occurrence of ST depressions considering age and different levels of LDL cholesterol and VLDL TG were given. The importance of simultaneous consideration of both VLDL TG and LDL cholesterol in ST segment depression was evident from the tables. Of other \"risk factors\" (BP, glucose tollerance, smoking, ESR) entered into the regression together with only age and the LPs, only ESR contributed with borderline significance to ST depressions.", "contents": "Studies in asymptomatic primary hyperlipidaemia. IV. ECG at rest and during exercise and its relation to various lipoprotein classes. Among approximately 20,000 apparently healthy subjects whose serum cholesterol and triglyceride (TG) values were screened at a health examination, those with the most pronounced hyperlipidaemia have been selected for further studies. Thus, 188 males and 126 females, aged 30-65 years, with asymptomatic primary hyperlipoproteinaemia (HLP) and 59 male and 69 female controls with non-elevated serum lipids were studied with regard to frequency of ST segment depressions during exercise to near maximal heart rate. Furthermore, the concentrations of cholesterol and TG were determined in the lipoprotein (LP) classes very low (VLDL), low (LDL) and high (HDL) density LP, separated by preparative ultracentrifugation. From the LP analysis each subject's HLP was classified according to the typing system of HLP recommended by the WHO. The frequency of ST depressions (Minnesota code 4.1-4.3 as well as 4.1-4.4) increased with age, was higher in females than in males and was increased in all types of HLP in males. The percentage frequencies of ST depressions 4.1-4.4 in the various types of HLP were (male/female, p against controls): controls 16/36, type IIA 50 (p less than 0.01)/56, type IIB 64 (p less than 0.01)/75 (p less than 0.01)/75 (p less than 0.05), type III 67 (p less than 0.01)/33 and type IV HLP 40 (p less than 0.01/53. There was no significant difference in the frequencies of ST depressions in subjects with \"high\" and \"low\" BP (hypertensives were excluded from the study) or in subjects with \"high\" and \"low\" k-value for the i.v. glucose tolerance. Non-smokers had a tendency to higher frequencies of ST depressions than smokers. The association between different LPs and other \"risk factors\" and the occurrence of ST depressions in HLP were studied further with multiple regression analysis. Invariably age was the best predictor of ST depressions. The LP fraction giving the highest correlation coefficient was LDL cholesterol in both sexes. VLDL TG and LDL TG were also positively and significantly associated with ST depressions. HDL cholesterol was negatively but insignificantly correlated to ST depressions. When age and LDL cholesterol had been entered into the multiple regression, the only factor giving further significance was VLDL TG in males. Probability tables for the occurrence of ST depressions considering age and different levels of LDL cholesterol and VLDL TG were given. The importance of simultaneous consideration of both VLDL TG and LDL cholesterol in ST segment depression was evident from the tables. Of other \"risk factors\" (BP, glucose tollerance, smoking, ESR) entered into the regression together with only age and the LPs, only ESR contributed with borderline significance to ST depressions."} {"id": "PMID:170801", "title": "Differential inhibition of phosphodiesterase according to the organ origin of the enzyme.", "content": "Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity.", "contents": "Differential inhibition of phosphodiesterase according to the organ origin of the enzyme. Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity."} {"id": "PMID:170805", "title": "Do sleep patterns relate to the desire for alcohol?", "content": "A measure of disposition to drink in alcoholics was developed using a progressive ratio schedule for reduction of delay in receiving a drink of two ounces of 95 proof ethanol. This measure showed increased disposition to drink during early abstinence compared to lab abstinence (more than seven days) during experimental intoxication compared to lab abstinence and shortly after a low dose drink during late abstinence. A multiple regression analysis of this measure for four subjects after alcohol withdrawal, showed significant effects for days abstinent and EEG sleep variables, particularly stage REM%. Low REM% was associated with high values for the disposition to drink. REM sleep deprivation, however, failed to significantly alter the measure of disposition to drink. Results are interpreted as supporting the hypotheses that sleep disturbances relate indirectly to the disposition to drink.", "contents": "Do sleep patterns relate to the desire for alcohol? A measure of disposition to drink in alcoholics was developed using a progressive ratio schedule for reduction of delay in receiving a drink of two ounces of 95 proof ethanol. This measure showed increased disposition to drink during early abstinence compared to lab abstinence (more than seven days) during experimental intoxication compared to lab abstinence and shortly after a low dose drink during late abstinence. A multiple regression analysis of this measure for four subjects after alcohol withdrawal, showed significant effects for days abstinent and EEG sleep variables, particularly stage REM%. Low REM% was associated with high values for the disposition to drink. REM sleep deprivation, however, failed to significantly alter the measure of disposition to drink. Results are interpreted as supporting the hypotheses that sleep disturbances relate indirectly to the disposition to drink."} {"id": "PMID:170810", "title": "Calcium pyrophosphate-induced pleurisy in rats: a new model of acute inflammation.", "content": "A model is described of acute inflammation in the pleural cavity of rats using calcium pyrophosphate as the irritant. This model would seem to simulate the pseudogout syndrome. It has been shown to be acute in onset, dominated by polymorphonuclear cells, complement independent. The advantage of the model is that volume of exudate, numbers and types of cells may be quantitated. Prostaglandins and cyclic AMP have been measured in the migrating cells. The significance of these findings has been discussed.", "contents": "Calcium pyrophosphate-induced pleurisy in rats: a new model of acute inflammation. A model is described of acute inflammation in the pleural cavity of rats using calcium pyrophosphate as the irritant. This model would seem to simulate the pseudogout syndrome. It has been shown to be acute in onset, dominated by polymorphonuclear cells, complement independent. The advantage of the model is that volume of exudate, numbers and types of cells may be quantitated. Prostaglandins and cyclic AMP have been measured in the migrating cells. The significance of these findings has been discussed."} {"id": "PMID:170813", "title": "A comparison of the relative rates of hemolysis induced by various fibrogenic and non-fibrogenic particles with washed rat erythrocytes in vitro.", "content": "Correlations between in vitro hemolytic activity and the in vivo fibrogenic activity of a number of particulate materials are demonstrated. Fibrogenic particles are capable of inducing hemolysis, while non-fibrogenic particles are not. It is suggested that particulates inducing a rate of hemolysis greater than 1 X 10(-4) min-1 may be fibrogenic.", "contents": "A comparison of the relative rates of hemolysis induced by various fibrogenic and non-fibrogenic particles with washed rat erythrocytes in vitro. Correlations between in vitro hemolytic activity and the in vivo fibrogenic activity of a number of particulate materials are demonstrated. Fibrogenic particles are capable of inducing hemolysis, while non-fibrogenic particles are not. It is suggested that particulates inducing a rate of hemolysis greater than 1 X 10(-4) min-1 may be fibrogenic."} {"id": "PMID:170814", "title": "Free silica analysis of environmental samples-a critical literature review.", "content": "The various analytical procedures for the analysis of free silica in environmental samples all suffer serious deficiencies, to the extent that there is no acceptable routine method. Each sample represents a minor research effort. Many of the uncertainties are related to an amorphous surface layer on quartz.", "contents": "Free silica analysis of environmental samples-a critical literature review. The various analytical procedures for the analysis of free silica in environmental samples all suffer serious deficiencies, to the extent that there is no acceptable routine method. Each sample represents a minor research effort. Many of the uncertainties are related to an amorphous surface layer on quartz."} {"id": "PMID:170815", "title": "1975 Yant Memorial Lecture New aspects on dust and pneumoconiosis research.", "content": "This lecture deals with pneumoconiosis, in particular with fibrotic tissue reactions caused by SiO2 and asbestos dusts in the lungs. The term \"fine dusts\" is defined in connection with the setting up of MAC-values. The aerodynamical diameter of particle shaped and fibrifom dust is set forth. Results of the fundamental research with SiO2, Coal mine and asbestos dusts in animal and cell experiments are explained.", "contents": "1975 Yant Memorial Lecture New aspects on dust and pneumoconiosis research. This lecture deals with pneumoconiosis, in particular with fibrotic tissue reactions caused by SiO2 and asbestos dusts in the lungs. The term \"fine dusts\" is defined in connection with the setting up of MAC-values. The aerodynamical diameter of particle shaped and fibrifom dust is set forth. Results of the fundamental research with SiO2, Coal mine and asbestos dusts in animal and cell experiments are explained."} {"id": "PMID:170816", "title": "Echocardiographic diagnosis of right atrial extension of Wilms' tumor.", "content": "A fourth case is presented of propagation of Wilms' tumor to the right atrium through the inferior vena cava. Ultrasonic examination of the heart was diagnostic of the tumor and the diagnosis was confirmed by angiographic studies and surgical exploration. This report provides the first echocardiographic description of a right atrial tumor in a child.", "contents": "Echocardiographic diagnosis of right atrial extension of Wilms' tumor. A fourth case is presented of propagation of Wilms' tumor to the right atrium through the inferior vena cava. Ultrasonic examination of the heart was diagnostic of the tumor and the diagnosis was confirmed by angiographic studies and surgical exploration. This report provides the first echocardiographic description of a right atrial tumor in a child."} {"id": "PMID:170817", "title": "Renewal of the epithelium in the descending colon of the mouse. IV. Cell population kinetics of vacuolated-columnar and mucous cells.", "content": "Proliferation and migration of cells in the vacuolated-columnar and mucous cell lines were studied in the descending colon of adult female mice given a single injection or a continuous infusion of 3H-thymidine and killed at various intervals from one hour to 12 days. This investigation was carried out using one mum-thick Epon sections which were radioautographed after staining with the periodic acid-Schiff technique and iron-hematoxylin. In the normalized crypts with ten equal segments, labeled vacuolated cells at one hour after injection of 3H-thymidine were encountered in the lower four segments and in decreasing numbers in segments 5 through 7. From the percent labeled cells in segments of the crypt, the birth rate and fluxes of cells were computed. Moreover, it was found that a cell in the vacuolated-columnar cell line would undergo three mitotic cycles on the average from its birth at the cryptal base to its extrusion from the surface; of these three cycles, the last one which took place from segment 3 to segment 7 appeared to be a changeover from dividing cells to non-dividing cells, in accordance with the \"slow cut-off\" model of Cairnie et al. ('65b). Mucous cells located in segments 1 through 6 of the crypt were capable of incorporating 3H-thymidine and thus capable of undergoing mitosis. However, the rate of turnover of mucous cells based on proliferative rate was found to be much lower than the rate of turnover of mucous cells based on the transit time in the non-dividing segments of the crypt. Since there was a concomitant overproduction of cells in the vacuolated cells and newly formed mucous cells in the lower portion of the crypt, it was concluded that some vacuolated cells would give rise to mucous cells. This putative transformation occurred in the lower four segments of the crypt. Mucous cells which were formed by transformation would migrate upward along the cryptal wall and accumulate more mucus in the theca; in doing so, they would undergo two divisions, on the average, before they became non-dividing mucous cells. In ascending the cryptal walls, both vacuolated-columnar cells and mucous cells appeared to migrate at a similar speed; they moved much slower at the base of the crypt and accelerated toward the upper portion of the crypt, but they migrated at a constant speed in the non-dividing segments of the crypt.", "contents": "Renewal of the epithelium in the descending colon of the mouse. IV. Cell population kinetics of vacuolated-columnar and mucous cells. Proliferation and migration of cells in the vacuolated-columnar and mucous cell lines were studied in the descending colon of adult female mice given a single injection or a continuous infusion of 3H-thymidine and killed at various intervals from one hour to 12 days. This investigation was carried out using one mum-thick Epon sections which were radioautographed after staining with the periodic acid-Schiff technique and iron-hematoxylin. In the normalized crypts with ten equal segments, labeled vacuolated cells at one hour after injection of 3H-thymidine were encountered in the lower four segments and in decreasing numbers in segments 5 through 7. From the percent labeled cells in segments of the crypt, the birth rate and fluxes of cells were computed. Moreover, it was found that a cell in the vacuolated-columnar cell line would undergo three mitotic cycles on the average from its birth at the cryptal base to its extrusion from the surface; of these three cycles, the last one which took place from segment 3 to segment 7 appeared to be a changeover from dividing cells to non-dividing cells, in accordance with the \"slow cut-off\" model of Cairnie et al. ('65b). Mucous cells located in segments 1 through 6 of the crypt were capable of incorporating 3H-thymidine and thus capable of undergoing mitosis. However, the rate of turnover of mucous cells based on proliferative rate was found to be much lower than the rate of turnover of mucous cells based on the transit time in the non-dividing segments of the crypt. Since there was a concomitant overproduction of cells in the vacuolated cells and newly formed mucous cells in the lower portion of the crypt, it was concluded that some vacuolated cells would give rise to mucous cells. This putative transformation occurred in the lower four segments of the crypt. Mucous cells which were formed by transformation would migrate upward along the cryptal wall and accumulate more mucus in the theca; in doing so, they would undergo two divisions, on the average, before they became non-dividing mucous cells. In ascending the cryptal walls, both vacuolated-columnar cells and mucous cells appeared to migrate at a similar speed; they moved much slower at the base of the crypt and accelerated toward the upper portion of the crypt, but they migrated at a constant speed in the non-dividing segments of the crypt."} {"id": "PMID:170818", "title": "Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis.", "content": "Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia.", "contents": "Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis. Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia."} {"id": "PMID:170819", "title": "Quantitative morphology and carbohydrate histochemistry of the mouse submandibular gland following prepubertal castration.", "content": "The endocrinologic basis for morphological and biochemical sex differences in the mouse submandibular gland have not been clarified. Previous studies have emphasized the maintenance of glandular differences in adult animals, rather than considering the factors responsible for their developmental etiology. Male CD-1 mice were castrated at intervals between 10 and 50 days of age and killed at 100 days. The quantitative development of granular tubules and the carbohydrate histochemistry of the submandibular glands were compared to untreated males and females. The area of granular tubules increased with age at castration. Nested analysis of variance indicated significant differences among treatments and among sections within individual glands. No group of castrated males had a greater development of tubules than untreated females. Carbohydrate histochemistry demonstrated an increase in carboxylated mucosubstances in the acinar cells and granular tubule cells of castrated animals.", "contents": "Quantitative morphology and carbohydrate histochemistry of the mouse submandibular gland following prepubertal castration. The endocrinologic basis for morphological and biochemical sex differences in the mouse submandibular gland have not been clarified. Previous studies have emphasized the maintenance of glandular differences in adult animals, rather than considering the factors responsible for their developmental etiology. Male CD-1 mice were castrated at intervals between 10 and 50 days of age and killed at 100 days. The quantitative development of granular tubules and the carbohydrate histochemistry of the submandibular glands were compared to untreated males and females. The area of granular tubules increased with age at castration. Nested analysis of variance indicated significant differences among treatments and among sections within individual glands. No group of castrated males had a greater development of tubules than untreated females. Carbohydrate histochemistry demonstrated an increase in carboxylated mucosubstances in the acinar cells and granular tubule cells of castrated animals."} {"id": "PMID:170820", "title": "Comparison of the adaptive changes in disaccharidase, glycolytic enzyme and fructosediphosphatase activities after intravenous and oral glucose in normal men.", "content": "Seven subjects were fed a 3,000 kcal defined formula diet daily for 19 days. Except for one 5-day period, 50% of the total caloric intake was provided as either oral or intravenous glucose. The study was divided into four periods as follows: period I lasted 5 days and provided 50% of calories as glucose; period II lasted 5 days and provided no carbohydrate (70% fat and 30% protein); period III lasted 4 days and provided 50% of calories as intravenous glucose and 50% of calories as oral fat plus protein; period IV lasted 5 days and provided 50% of calories as oral glucose. Intestinal biopsy specimens were taken on days 3 and 5 of each period, except period III when biopsies were done only on day 4. No change in intestinal morphology occurred during the study. The carbohydrate-free diet caused the alpha-glucosidase (maltase and sucrase) activities to decrease significantly from that seen with the glucose diet. Sucrase decreased from 14.4 +/- 1.0 to 7.1 +/- 0.9 mumoles/min per g tissue and maltase decreased from 56.1 +/- 3.4 to 30.0 +/- 2.1 mumoles/min per g tissue. Glycolytic enzyme activities decreased during the carbohydrate-free period (pyruvate kinase decreased from 236 +/- 12 to 78 +/- 8, fructose 1-phosphate aldolase decreased from 147 +/- 6 to 53 +/- 4, fructose-1,6-diphosphate aldolase decreased from 151 +/- 8 to 55 +/- 3, and hexokinase decreased from 21 +/- 3 to 7 +/- 1 nmoles/min per mg protein, respectively). Intravenous glucose caused no change in disaccharidase activities. The enzyme activities during periods I and IV were identical and significantly higher than during period II with the exception of fructose-1,6-diphosphatase which increased during period II as compared with periods I and IV. These findings provide an explanation for the transient period of decreased tolerance to dietary sugars when patients are weaned from total parenteral feedings to enteral feedings.", "contents": "Comparison of the adaptive changes in disaccharidase, glycolytic enzyme and fructosediphosphatase activities after intravenous and oral glucose in normal men. Seven subjects were fed a 3,000 kcal defined formula diet daily for 19 days. Except for one 5-day period, 50% of the total caloric intake was provided as either oral or intravenous glucose. The study was divided into four periods as follows: period I lasted 5 days and provided 50% of calories as glucose; period II lasted 5 days and provided no carbohydrate (70% fat and 30% protein); period III lasted 4 days and provided 50% of calories as intravenous glucose and 50% of calories as oral fat plus protein; period IV lasted 5 days and provided 50% of calories as oral glucose. Intestinal biopsy specimens were taken on days 3 and 5 of each period, except period III when biopsies were done only on day 4. No change in intestinal morphology occurred during the study. The carbohydrate-free diet caused the alpha-glucosidase (maltase and sucrase) activities to decrease significantly from that seen with the glucose diet. Sucrase decreased from 14.4 +/- 1.0 to 7.1 +/- 0.9 mumoles/min per g tissue and maltase decreased from 56.1 +/- 3.4 to 30.0 +/- 2.1 mumoles/min per g tissue. Glycolytic enzyme activities decreased during the carbohydrate-free period (pyruvate kinase decreased from 236 +/- 12 to 78 +/- 8, fructose 1-phosphate aldolase decreased from 147 +/- 6 to 53 +/- 4, fructose-1,6-diphosphate aldolase decreased from 151 +/- 8 to 55 +/- 3, and hexokinase decreased from 21 +/- 3 to 7 +/- 1 nmoles/min per mg protein, respectively). Intravenous glucose caused no change in disaccharidase activities. The enzyme activities during periods I and IV were identical and significantly higher than during period II with the exception of fructose-1,6-diphosphatase which increased during period II as compared with periods I and IV. These findings provide an explanation for the transient period of decreased tolerance to dietary sugars when patients are weaned from total parenteral feedings to enteral feedings."} {"id": "PMID:170822", "title": "Fatal disseminated adenovirus infection in a renal transplant recipient.", "content": "A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.", "contents": "Fatal disseminated adenovirus infection in a renal transplant recipient. A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group."} {"id": "PMID:170824", "title": "Placental insufficiency in relation to postterm pregnancy and fetal postmaturity. Evaluation of fetoplacental function; management of the postterm gravida.", "content": "As pregnancy extends post term, incidence of placental insufficiency, fetal postmaturity (dysmaturity), and fetal perinatal death increases rapidly as a consequence of reduced respiratory and nutritive placental function. Despite a compensatory fetoplacental respiratory reserve capacity, fetal distress is observed in about one third of postterm pregnancies. On a biochemical level, placental pathophysiology in postterm-postmaturity pregnancies is not well understood. Postmaturity is correlated with increased incidence of placental lesions, fetal hypoxia-asphyxia, intrauterine growth retardation, increased perinatal death, and neonatal morbidity. Early diagnosis of fetal postmaturity is difficult because currently applied test methods allow recognition only when placental insufficiency is far progressed. Therefore, in postterm gravidas with a favorable cervix, induction of labor should be considered; in older primigravidas, in whom fetal losses may be sevenfold increased, or in multiparas with a history of obstetric complications, pregnancy may require termination by cesarean section. Pregnancy may be allowed to continue under close supervision in cases of uncertainty of duration of gestation, in gravidas carrying small babies, in young primigravidas, and in multigravidas in whom placentofetal function tests are normal. As long as fetal scalp blood sampling during labor does not show fetal acidosis, despite abnormal fetal heart rate pattern and meconium release, vaginal delivery may be attempted when deemed possible within a few hours. In parturients attention must be paid to the extent of uterine activity and type of medication; lateral positioning of the gravida and maternal oxygen breathing, facilitating fetal oxygen supply, are important features. Because during bearing-down efforts placentofetal respiratory reserves of postterm gravidas may become further compromised, immediate delivery by forceps or vacuum extraction may be considered. After delivery the umbilical cord should not be clamped immediately in order to allow increased fetal blood supply and to counteract fetal hypovolemia. Dysmature newborn infants require special care by the neonatologist.", "contents": "Placental insufficiency in relation to postterm pregnancy and fetal postmaturity. Evaluation of fetoplacental function; management of the postterm gravida. As pregnancy extends post term, incidence of placental insufficiency, fetal postmaturity (dysmaturity), and fetal perinatal death increases rapidly as a consequence of reduced respiratory and nutritive placental function. Despite a compensatory fetoplacental respiratory reserve capacity, fetal distress is observed in about one third of postterm pregnancies. On a biochemical level, placental pathophysiology in postterm-postmaturity pregnancies is not well understood. Postmaturity is correlated with increased incidence of placental lesions, fetal hypoxia-asphyxia, intrauterine growth retardation, increased perinatal death, and neonatal morbidity. Early diagnosis of fetal postmaturity is difficult because currently applied test methods allow recognition only when placental insufficiency is far progressed. Therefore, in postterm gravidas with a favorable cervix, induction of labor should be considered; in older primigravidas, in whom fetal losses may be sevenfold increased, or in multiparas with a history of obstetric complications, pregnancy may require termination by cesarean section. Pregnancy may be allowed to continue under close supervision in cases of uncertainty of duration of gestation, in gravidas carrying small babies, in young primigravidas, and in multigravidas in whom placentofetal function tests are normal. As long as fetal scalp blood sampling during labor does not show fetal acidosis, despite abnormal fetal heart rate pattern and meconium release, vaginal delivery may be attempted when deemed possible within a few hours. In parturients attention must be paid to the extent of uterine activity and type of medication; lateral positioning of the gravida and maternal oxygen breathing, facilitating fetal oxygen supply, are important features. Because during bearing-down efforts placentofetal respiratory reserves of postterm gravidas may become further compromised, immediate delivery by forceps or vacuum extraction may be considered. After delivery the umbilical cord should not be clamped immediately in order to allow increased fetal blood supply and to counteract fetal hypovolemia. Dysmature newborn infants require special care by the neonatologist."} {"id": "PMID:170825", "title": "The epidemiology and interrelationship of cervical dysplasia and type 2 herpesvirus in a low-income housing project.", "content": "This report examines the association between cervical dysplasia and herpes simplex virus type 2 antibodies in a low-income housing project, Atlanta, Georgia. We established a clinic in this project at which women could receive a breast examination and Papanicolaou smear and have blood drawn to be tested for herpesvirus type 2 antibodies. Prevalence of herpesvirus rose sharply as age increased. There was a significant absence of antibodies in young, nulliparous women. Dysplasia showed a tendency to be related to age, age at first pregnancy, and total number of pregnancies. None of these associations was significant. The major finding of the study was that the 15- to 24-year-old women with herpesvirus had a relative risk of 5.44 of having cervical dysplasia compared to women without herpesvirus antibodies. these data are consistent with the concept that herpesvirus infections may be etiologically related to the initiation of cervical neoplasia. However, a cohort study is needed to determine whether herpes infection precedes or follows the earliest neoplastic changes.", "contents": "The epidemiology and interrelationship of cervical dysplasia and type 2 herpesvirus in a low-income housing project. This report examines the association between cervical dysplasia and herpes simplex virus type 2 antibodies in a low-income housing project, Atlanta, Georgia. We established a clinic in this project at which women could receive a breast examination and Papanicolaou smear and have blood drawn to be tested for herpesvirus type 2 antibodies. Prevalence of herpesvirus rose sharply as age increased. There was a significant absence of antibodies in young, nulliparous women. Dysplasia showed a tendency to be related to age, age at first pregnancy, and total number of pregnancies. None of these associations was significant. The major finding of the study was that the 15- to 24-year-old women with herpesvirus had a relative risk of 5.44 of having cervical dysplasia compared to women without herpesvirus antibodies. these data are consistent with the concept that herpesvirus infections may be etiologically related to the initiation of cervical neoplasia. However, a cohort study is needed to determine whether herpes infection precedes or follows the earliest neoplastic changes."} {"id": "PMID:170826", "title": "Evaluation of serum progesterone during treatment of malignant trophoblastic disease.", "content": "Serial assays of serum progesterone and serum human chorionic gonadotropin (HCG) were performed in eight cases of choriocarcinoma before and during treatment of the disease. Serum progesterone was measured by the competitive protein-binding technique and serum HCG was measured by the hemagglutination inhibition method. Serum HCG gives a better index of response of the tumor to treatment when compared to serum progesterone. In cases where the ovaries are still present serum progesterone does not disappear completely when the disease is eradicated and fluctuates cyclically, thus reflecting ovarian activity. However, in most cases with pulmonary secondaries, serum progesterone was elevated in spite of undetectable serum HCG. With widespread metastases serum progesterone rose to pregnancy levels and remained persistently high. Cerebrospinal fluid progesterone in a case of choriocarcinoma with cerebral metastasis was 5 ng. per milliliter, which was very much higher than in normal pregnant subjects. The findings of serum progesterone in comparison to serum HCG during therapy of choriocarcinoma are discussed.", "contents": "Evaluation of serum progesterone during treatment of malignant trophoblastic disease. Serial assays of serum progesterone and serum human chorionic gonadotropin (HCG) were performed in eight cases of choriocarcinoma before and during treatment of the disease. Serum progesterone was measured by the competitive protein-binding technique and serum HCG was measured by the hemagglutination inhibition method. Serum HCG gives a better index of response of the tumor to treatment when compared to serum progesterone. In cases where the ovaries are still present serum progesterone does not disappear completely when the disease is eradicated and fluctuates cyclically, thus reflecting ovarian activity. However, in most cases with pulmonary secondaries, serum progesterone was elevated in spite of undetectable serum HCG. With widespread metastases serum progesterone rose to pregnancy levels and remained persistently high. Cerebrospinal fluid progesterone in a case of choriocarcinoma with cerebral metastasis was 5 ng. per milliliter, which was very much higher than in normal pregnant subjects. The findings of serum progesterone in comparison to serum HCG during therapy of choriocarcinoma are discussed."} {"id": "PMID:170827", "title": "Intrauterine pressure wave form characteristics in hypocontractile labor before and after oxytocin administration.", "content": "The data demonstrate that the contractions of hypocontractile active labor and normal spontaneous labor are different in several measures in addition to maximal amplitude. Furthermore, when the pathophysiology is corrected by the use of oxytocin, the contractions resemble those of normal spontaneous labor except in the maximal rate of tension development. Our data tend to support the subcellular model of uterine contractility, although the incompleteness of these models limits interpretation.", "contents": "Intrauterine pressure wave form characteristics in hypocontractile labor before and after oxytocin administration. The data demonstrate that the contractions of hypocontractile active labor and normal spontaneous labor are different in several measures in addition to maximal amplitude. Furthermore, when the pathophysiology is corrected by the use of oxytocin, the contractions resemble those of normal spontaneous labor except in the maximal rate of tension development. Our data tend to support the subcellular model of uterine contractility, although the incompleteness of these models limits interpretation."} {"id": "PMID:170828", "title": "Purification of human placental estradiol 17 beta-dehydrogenase study of the steroid-binding site.", "content": "Human placental estradiol 17 beta-dehydrogenase has been purified by affinity chromatography. The purified enzyme is homogenous by polyacrylamide-gel electrophoresis. To study topography of the steroid-binding site, 16 alpha-bromoacetoxyestradiol 3-methyl ether was synthesized with estriol 3-methyl ether, bromoacetic acid, or [2-3H] bromoacetic acid and dicyclohexylcarbodiimide. The steroid alkylates cysteine, histidine, methionine, and tryptophan under physiologic conditions. Being a substrate of the enzyme, it must bind at the steroid-binding site. The steroid inactivates the enzyme in a time-dependent, irreversible manner. Inactivation of the enzyme by excess 16 alpha-bromoacetoxyestradiol 3-methyl ether follows pseudo--first-order kinetics with t1/2 = 1.5 hours. Amino acid analysis reveals that a histidyl residue is carboxymethylated. Estradiol-17 beta slows inactivation; 2-mercaptoethanol stops it. Previous studies have shown a histidyl residue also present at the catalytic region of the active site of 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans. It is tempting to consider that these histidyl residues may be an essential component for the dehydrogenation of the steroid substrates.", "contents": "Purification of human placental estradiol 17 beta-dehydrogenase study of the steroid-binding site. Human placental estradiol 17 beta-dehydrogenase has been purified by affinity chromatography. The purified enzyme is homogenous by polyacrylamide-gel electrophoresis. To study topography of the steroid-binding site, 16 alpha-bromoacetoxyestradiol 3-methyl ether was synthesized with estriol 3-methyl ether, bromoacetic acid, or [2-3H] bromoacetic acid and dicyclohexylcarbodiimide. The steroid alkylates cysteine, histidine, methionine, and tryptophan under physiologic conditions. Being a substrate of the enzyme, it must bind at the steroid-binding site. The steroid inactivates the enzyme in a time-dependent, irreversible manner. Inactivation of the enzyme by excess 16 alpha-bromoacetoxyestradiol 3-methyl ether follows pseudo--first-order kinetics with t1/2 = 1.5 hours. Amino acid analysis reveals that a histidyl residue is carboxymethylated. Estradiol-17 beta slows inactivation; 2-mercaptoethanol stops it. Previous studies have shown a histidyl residue also present at the catalytic region of the active site of 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans. It is tempting to consider that these histidyl residues may be an essential component for the dehydrogenation of the steroid substrates."} {"id": "PMID:170829", "title": "Effects of estrogens on systemic and regional circulations in normal and renal hypertensive sheep.", "content": "Effects of estrogen administration on systemic and regional circulation were studied in normotensive and renal hypertensive, chronically instrumented nonpregnant and pregnant ewes. Arterial pressure, cardiac output, and uterine, renal, superior mesenteric, and iliac blood flows, as well as uterine oxygen transfer, were monitored before and after intravenous administration of Premarin or estradiol-17 beta. The results show that: (1) estrogen administration produces a marked decrease in uterine vascular resistance and increase in uterine blood flow and oxygen transfer, lasting for about 2 hours; (2) arterial pressure, cardiac output, and other regional blood flows were not affected by estrogens; (3) the magnitude of uterine vasodilatation produced by estrogens was greater in the hypertensive than in the normotensive animals; it was also greater in the nonpregnant than in the pregnant state; these findings indicate that the magnitude of uterine vasodilatation depends on the status of the uterine vascular resistance in the resting state; (4) blockade of the autonomic nervous system at various levels, as well as administration of a mild antihistaminic agent, failed to alter the magnitude of the estrogen-induced uterine vasodilatation. These results indicate that estrogens act directly on the uterine vascular bed and produce a redistribution of flows and resistances in the body; the precise sites of this redistribution are not as yet determined.", "contents": "Effects of estrogens on systemic and regional circulations in normal and renal hypertensive sheep. Effects of estrogen administration on systemic and regional circulation were studied in normotensive and renal hypertensive, chronically instrumented nonpregnant and pregnant ewes. Arterial pressure, cardiac output, and uterine, renal, superior mesenteric, and iliac blood flows, as well as uterine oxygen transfer, were monitored before and after intravenous administration of Premarin or estradiol-17 beta. The results show that: (1) estrogen administration produces a marked decrease in uterine vascular resistance and increase in uterine blood flow and oxygen transfer, lasting for about 2 hours; (2) arterial pressure, cardiac output, and other regional blood flows were not affected by estrogens; (3) the magnitude of uterine vasodilatation produced by estrogens was greater in the hypertensive than in the normotensive animals; it was also greater in the nonpregnant than in the pregnant state; these findings indicate that the magnitude of uterine vasodilatation depends on the status of the uterine vascular resistance in the resting state; (4) blockade of the autonomic nervous system at various levels, as well as administration of a mild antihistaminic agent, failed to alter the magnitude of the estrogen-induced uterine vasodilatation. These results indicate that estrogens act directly on the uterine vascular bed and produce a redistribution of flows and resistances in the body; the precise sites of this redistribution are not as yet determined."} {"id": "PMID:170830", "title": "Fibrous histiocytoma of the corneoscleral limbus.", "content": "A 21-year-old white woman had an apparently benign fibrous histiocytoma at the corneoscleral limbus. By histopathologic and ultrastructural studies, the tumor consisted of lipid-containing histiocytes and fibrocytic cells arranged in a storiform configuration with a collagenous interstitium. After an excision, the lesion gradually decreased in size and did not recur in a five-month follow-up period.", "contents": "Fibrous histiocytoma of the corneoscleral limbus. A 21-year-old white woman had an apparently benign fibrous histiocytoma at the corneoscleral limbus. By histopathologic and ultrastructural studies, the tumor consisted of lipid-containing histiocytes and fibrocytic cells arranged in a storiform configuration with a collagenous interstitium. After an excision, the lesion gradually decreased in size and did not recur in a five-month follow-up period."} {"id": "PMID:170831", "title": "Clinical and immunologic responses in patients with viral keratoconjunctivitis.", "content": "Of 120 individuals suffering from follicular conjunctivitis, with or without keratitis, 56 had epidemic keratoconjunctivitis caused by adenovirus type 8. The remaining 64 patients had keratoconjunctivitis produced by several different viruses, including herpes simplex, adenoviruses types 3, 7, 8, 16, 21, and 29, and others. Positive viral cultures were difficult to obtain after the first week of illness in most viral infections. Serologic tests were far more successful in indetifying causative agents. Hemagglutination-inhibition tests in adenovirus infections proved to be fast, accurate, and more sensitive than other serologic tests. Among the epidemic and nonepidemic adenovirus groups, the degree of corneal involvement in the infections appeared to be correlated with the level antibody against the infectious agent. Patients with low antibody titers had more severe keratitis than those with high titers. This correlation was true for both the epidemic and non epidemic patients.", "contents": "Clinical and immunologic responses in patients with viral keratoconjunctivitis. Of 120 individuals suffering from follicular conjunctivitis, with or without keratitis, 56 had epidemic keratoconjunctivitis caused by adenovirus type 8. The remaining 64 patients had keratoconjunctivitis produced by several different viruses, including herpes simplex, adenoviruses types 3, 7, 8, 16, 21, and 29, and others. Positive viral cultures were difficult to obtain after the first week of illness in most viral infections. Serologic tests were far more successful in indetifying causative agents. Hemagglutination-inhibition tests in adenovirus infections proved to be fast, accurate, and more sensitive than other serologic tests. Among the epidemic and nonepidemic adenovirus groups, the degree of corneal involvement in the infections appeared to be correlated with the level antibody against the infectious agent. Patients with low antibody titers had more severe keratitis than those with high titers. This correlation was true for both the epidemic and non epidemic patients."} {"id": "PMID:170833", "title": "Intralysosomal formation of amyloid fibrils.", "content": "Unusual inclusions, which occurred in the reticuloendothelial cells intimately associated with fresh amyloid deposits, were analyzed by electron microscopy. The inclusions were located in the areas rich in the primary lysosome type of dense bodies and the cytoplasmic invaginations containing well-oriented amyloid fibrils. They were single-membrane-bounded, measured 0.3 to 0.8 mu in width and 0.5 to several microns in length, and showed considerable variation in the electron density of their contents. The latter consisted of two different ultrastructural elements: fibrillar profiles and a homogeneous or finely granular electron-dense substance. The fibrillar profiles were virtually identical in ulstrastructure to the amyloid fibrils and were well-oriented parallel to the long axis of the inclusion. The homogeneous or finely granular electron-dense substance appeared to be comparable to that composing the dense body matrix. The inclusions were usually acid phosphatase positive, but did not take up intravenously injected Thorotrast particles. These data led us to conclude that these inclusions were transitional forms from the usual dense bodies to the deep cytoplasmic invaginations containing well-oriented amyloid fibrils (which are accepted by most investigators as the sites of amyloid formation) and thus constitute direct evidence for the involvement of lysosomes in amyloid fibril formation.", "contents": "Intralysosomal formation of amyloid fibrils. Unusual inclusions, which occurred in the reticuloendothelial cells intimately associated with fresh amyloid deposits, were analyzed by electron microscopy. The inclusions were located in the areas rich in the primary lysosome type of dense bodies and the cytoplasmic invaginations containing well-oriented amyloid fibrils. They were single-membrane-bounded, measured 0.3 to 0.8 mu in width and 0.5 to several microns in length, and showed considerable variation in the electron density of their contents. The latter consisted of two different ultrastructural elements: fibrillar profiles and a homogeneous or finely granular electron-dense substance. The fibrillar profiles were virtually identical in ulstrastructure to the amyloid fibrils and were well-oriented parallel to the long axis of the inclusion. The homogeneous or finely granular electron-dense substance appeared to be comparable to that composing the dense body matrix. The inclusions were usually acid phosphatase positive, but did not take up intravenously injected Thorotrast particles. These data led us to conclude that these inclusions were transitional forms from the usual dense bodies to the deep cytoplasmic invaginations containing well-oriented amyloid fibrils (which are accepted by most investigators as the sites of amyloid formation) and thus constitute direct evidence for the involvement of lysosomes in amyloid fibril formation."} {"id": "PMID:170834", "title": "Mechanism of lymphoma cell death induced by cyclic AMP.", "content": "A mouse lymphoma tissue culture line, S49, is killed by isoproterenol, choleratoxin, or prostaglandin E1, inducers of cyclic AMP (cAMP) in these cells, or by the analog dibutyryl (db) cAMP. Cell death follows arrest in the G1 phase of the cell cycle. Mutant subclones obtained by growing S49 with dbcAMP were resistant to killing. They were deficient in cAMP-dependent protein kinase. These results are discussed in relation to the possible physiologic role of cAMP-induced cell death in T-cell differentiation.", "contents": "Mechanism of lymphoma cell death induced by cyclic AMP. A mouse lymphoma tissue culture line, S49, is killed by isoproterenol, choleratoxin, or prostaglandin E1, inducers of cyclic AMP (cAMP) in these cells, or by the analog dibutyryl (db) cAMP. Cell death follows arrest in the G1 phase of the cell cycle. Mutant subclones obtained by growing S49 with dbcAMP were resistant to killing. They were deficient in cAMP-dependent protein kinase. These results are discussed in relation to the possible physiologic role of cAMP-induced cell death in T-cell differentiation."} {"id": "PMID:170836", "title": "Intraperitoneal oxygen and carbon dioxide tensions in experimental adhesion disease and peritonitis.", "content": "Intraperitoneal oxygen and carbon dioxide tensions were studied in rats during silica-induced adhesion formation or fecal peritonitis. Measurements of PO2 and PCO2 in the abdominal cavity were performed by means of an implanted Silastic tonometer. During active adhesion formation one to three weeks after administration of silica, the intra-abdominal PO2 decreased by 50 per cent from normal whereas the intra-abdominal PCO2 and the rate of oxygen consumption in the peritoneum were elevated. Progressing peritonitis also resulted in decreased intraperitoneal PO2 and increased accumulation of carbon dioxide in the peritoneal cavity. In rats with peritonitis the rate of oxygen consumption in the peritoneal exudate clearly exceeded that in the peritoneal membrane.", "contents": "Intraperitoneal oxygen and carbon dioxide tensions in experimental adhesion disease and peritonitis. Intraperitoneal oxygen and carbon dioxide tensions were studied in rats during silica-induced adhesion formation or fecal peritonitis. Measurements of PO2 and PCO2 in the abdominal cavity were performed by means of an implanted Silastic tonometer. During active adhesion formation one to three weeks after administration of silica, the intra-abdominal PO2 decreased by 50 per cent from normal whereas the intra-abdominal PCO2 and the rate of oxygen consumption in the peritoneum were elevated. Progressing peritonitis also resulted in decreased intraperitoneal PO2 and increased accumulation of carbon dioxide in the peritoneal cavity. In rats with peritonitis the rate of oxygen consumption in the peritoneal exudate clearly exceeded that in the peritoneal membrane."} {"id": "PMID:170837", "title": "Ligation of a branch of the portal vein for carcinoma of the liver.", "content": "Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver.", "contents": "Ligation of a branch of the portal vein for carcinoma of the liver. Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver."} {"id": "PMID:170838", "title": "Epstein-Barr Virus antibodies in patients with carcinoma of the nasopharynx and carcinoma of other sites in the head and neck.", "content": "Serum antibody titers to Epstein-Barr virus were significantly elevated in a group of twenty-three patients with nasopharyngeal carcinoma as compared with eighty-six patients with cancer of other sites in the head and neck and 222 age-matched controls. Our findings in this group of patients support the suggestion of an association between the Epstein-Barr virus and nasopharyngeal carcinoma.", "contents": "Epstein-Barr Virus antibodies in patients with carcinoma of the nasopharynx and carcinoma of other sites in the head and neck. Serum antibody titers to Epstein-Barr virus were significantly elevated in a group of twenty-three patients with nasopharyngeal carcinoma as compared with eighty-six patients with cancer of other sites in the head and neck and 222 age-matched controls. Our findings in this group of patients support the suggestion of an association between the Epstein-Barr virus and nasopharyngeal carcinoma."} {"id": "PMID:170840", "title": "Sebaceous cell carcinoma of the parotid gland.", "content": "Sebaceous cell carcinoma of the parotid gland is a rare lesion. A review of the English literature reveals nine previously reported cases. Two cases are presented in which the tumor was originally diagnosed as mucoepidermoid carcinoma. Aggressive treatment of the recurrence, which was subsequently recognized as sebaceous cell carcinoma has resulted in apparent cure. Histologic features and possible histogenesis are discussed.", "contents": "Sebaceous cell carcinoma of the parotid gland. Sebaceous cell carcinoma of the parotid gland is a rare lesion. A review of the English literature reveals nine previously reported cases. Two cases are presented in which the tumor was originally diagnosed as mucoepidermoid carcinoma. Aggressive treatment of the recurrence, which was subsequently recognized as sebaceous cell carcinoma has resulted in apparent cure. Histologic features and possible histogenesis are discussed."} {"id": "PMID:170841", "title": "Pre-operative neutralization of gastric acidity.", "content": "The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent.", "contents": "Pre-operative neutralization of gastric acidity. The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent."} {"id": "PMID:170843", "title": "Cytoplasmic inclusions of neurons in the monkey visual cortex (area 19).", "content": "Several unusual neuronal inclusions were found in certain cells of the rhesus monkey visual cortex (Area 19): 1. Filamentous bodies, present in the small stellate cells of layer IV, globoid, 0.3-0.6 mum in diameter, consisting of fine 50 A filaments in a hexagonal meshwork. These are often associated with the labyrinthine bodies. 2. Labyrinthine bodies found exclusively in the small stellate cells of layer IV, including certain neurons with dispersed ribosomes. These are 0.4-0.7 mum in diameter and consist of 900 A wide tubes which interconnect with one another. The walls of these tubes are continuous and made up of a sheet or honeycomb lacework of small hexagonal 150 A subunits. 3. This inclusion, an aggregate 0.3-0.7 mum in size, consists of small membrane-bounded vesicles with a single dense granule associated with other non-membrane bound small dense droplets. The inclusions are always associated with the maturing face of the Golgi complex of certain layer IV pyramidal cells; as such, they may be an unusual product of the Golgi apparatus. These observations were confirmed by examination of stereo pairs of electron micrographs. Speculations are made with regard to possible functions for these inclusions.", "contents": "Cytoplasmic inclusions of neurons in the monkey visual cortex (area 19). Several unusual neuronal inclusions were found in certain cells of the rhesus monkey visual cortex (Area 19): 1. Filamentous bodies, present in the small stellate cells of layer IV, globoid, 0.3-0.6 mum in diameter, consisting of fine 50 A filaments in a hexagonal meshwork. These are often associated with the labyrinthine bodies. 2. Labyrinthine bodies found exclusively in the small stellate cells of layer IV, including certain neurons with dispersed ribosomes. These are 0.4-0.7 mum in diameter and consist of 900 A wide tubes which interconnect with one another. The walls of these tubes are continuous and made up of a sheet or honeycomb lacework of small hexagonal 150 A subunits. 3. This inclusion, an aggregate 0.3-0.7 mum in size, consists of small membrane-bounded vesicles with a single dense granule associated with other non-membrane bound small dense droplets. The inclusions are always associated with the maturing face of the Golgi complex of certain layer IV pyramidal cells; as such, they may be an unusual product of the Golgi apparatus. These observations were confirmed by examination of stereo pairs of electron micrographs. Speculations are made with regard to possible functions for these inclusions."} {"id": "PMID:170845", "title": "Re-evaluation of dosage and duration of action of d-tubocurarine in the pediatric age group.", "content": "A cumulative dose-response curve for d-tubocurarine based on body weight was determined for 44 infants and children 1 day to 7 years of age during halothane, nitrous oxide and oxygen anesthesia. Depression of thumb adduction was measured. Age difference did not affect the mean dose-effect response. Infants less than 10 days old, however, showed the wideest deviation of responses. When the effect of d-tubocurarine is determined by twitch response, infants and children are more resistant to d-tubocurarine and recover faster than adults from similar levels of neuromuscular depression. Monitoring of neuromuscular function by train-of-four stimulation proved as useful as it is in adults.", "contents": "Re-evaluation of dosage and duration of action of d-tubocurarine in the pediatric age group. A cumulative dose-response curve for d-tubocurarine based on body weight was determined for 44 infants and children 1 day to 7 years of age during halothane, nitrous oxide and oxygen anesthesia. Depression of thumb adduction was measured. Age difference did not affect the mean dose-effect response. Infants less than 10 days old, however, showed the wideest deviation of responses. When the effect of d-tubocurarine is determined by twitch response, infants and children are more resistant to d-tubocurarine and recover faster than adults from similar levels of neuromuscular depression. Monitoring of neuromuscular function by train-of-four stimulation proved as useful as it is in adults."} {"id": "PMID:170842", "title": "Clinical evaluation of the action of dexamethasone.", "content": "The antioedematous action of dexamethasone was assessed in 28 patients with supratentorial and infratentorial intracranial tumours and craniocerebral trauma. The criteria of evaluation included the state of consciousness, signs of focal cerebral injury, autonomic disturbances and signs of raised intracranial pressure. The greatest improvement was obtained in patients having intracranial tumours with herniation of the brain stem. In cases of extensive craniocerebral trauma no evident improvement was achieved.", "contents": "Clinical evaluation of the action of dexamethasone. The antioedematous action of dexamethasone was assessed in 28 patients with supratentorial and infratentorial intracranial tumours and craniocerebral trauma. The criteria of evaluation included the state of consciousness, signs of focal cerebral injury, autonomic disturbances and signs of raised intracranial pressure. The greatest improvement was obtained in patients having intracranial tumours with herniation of the brain stem. In cases of extensive craniocerebral trauma no evident improvement was achieved."} {"id": "PMID:170851", "title": "[The structure of biological membranes: localization of sulfoquinovosyldiglyceride in various membranes of chloroplasts using specific antibodies].", "content": "The sulfoquinovosyl pole of at least a part of the sulfolipid molecule, in the envelope and the thylakoids of chloroplasts, is accessible to the specific antibody. Agglutination of the chloroplasts is due to the sulfolipid which is located on the envelope and uniformly distributed on the external surface. Reactivity of the sulfolipid located on the membrane of thylakoids, when exposed to the corresponding antibody, appears to be different from the sulfolipid reactivity of the envelope: the antibody fails to agglutinate the thylakoids. Thylakoids altered by osmotic chock are sensitized to agglutination. Immunoenzymatic studies followed by electron microscopy revealed the presence of the sulfolipid on the membrane of the various thylakoids. The local reactions did not appear to be continous.", "contents": "[The structure of biological membranes: localization of sulfoquinovosyldiglyceride in various membranes of chloroplasts using specific antibodies]. The sulfoquinovosyl pole of at least a part of the sulfolipid molecule, in the envelope and the thylakoids of chloroplasts, is accessible to the specific antibody. Agglutination of the chloroplasts is due to the sulfolipid which is located on the envelope and uniformly distributed on the external surface. Reactivity of the sulfolipid located on the membrane of thylakoids, when exposed to the corresponding antibody, appears to be different from the sulfolipid reactivity of the envelope: the antibody fails to agglutinate the thylakoids. Thylakoids altered by osmotic chock are sensitized to agglutination. Immunoenzymatic studies followed by electron microscopy revealed the presence of the sulfolipid on the membrane of the various thylakoids. The local reactions did not appear to be continous."} {"id": "PMID:170850", "title": "Mechanism of action of neurotoxins.", "content": "This paper is a summary of studies over the past few years that pertain to animal neurotoxins. These toxins are found throughout the animal kingdom. Homologies exist in the structures of these poisons within classes and point to conservation of active sites throughout evolution. In the case of the peptides, invariant amino acids may be involved in the active site, be essential for maintaining the shape and conformation of the molecule or serve as a fulcrum for folding of the peptide chain after synthesis. At the nuclear or DNA-level, a constant base sequence may regulate gene operation so that only a specific amino acid is coded. Physiologically, and with ultrastructural and biochemical correlation, the predominant mode of action of neurotoxins relate to one or the other of the major activities of the excitable cell,--on conductile activity affecting Na+ or K+ permeabilities, on output or secretory activities affecting the release of neurotransmitter or on in put generator activities affecting the receptor molecules for transmitter themselves. The future of these animal neurotoxins in neurobiological research is secure. The elucidation of molecular mechanisms, by which these various physiological activities of excitable tissue are expressed, will surely involve one or more of these fascinating, naturally-occurring compounds.", "contents": "Mechanism of action of neurotoxins. This paper is a summary of studies over the past few years that pertain to animal neurotoxins. These toxins are found throughout the animal kingdom. Homologies exist in the structures of these poisons within classes and point to conservation of active sites throughout evolution. In the case of the peptides, invariant amino acids may be involved in the active site, be essential for maintaining the shape and conformation of the molecule or serve as a fulcrum for folding of the peptide chain after synthesis. At the nuclear or DNA-level, a constant base sequence may regulate gene operation so that only a specific amino acid is coded. Physiologically, and with ultrastructural and biochemical correlation, the predominant mode of action of neurotoxins relate to one or the other of the major activities of the excitable cell,--on conductile activity affecting Na+ or K+ permeabilities, on output or secretory activities affecting the release of neurotransmitter or on in put generator activities affecting the receptor molecules for transmitter themselves. The future of these animal neurotoxins in neurobiological research is secure. The elucidation of molecular mechanisms, by which these various physiological activities of excitable tissue are expressed, will surely involve one or more of these fascinating, naturally-occurring compounds."} {"id": "PMID:170853", "title": "[Determination of the penicillin acylase activity of E. coli cultures using a method of gas-liquid chromatography].", "content": "Penicillinacylase activity was determined in E. coli by the product of benzylpenicillin destruction, i.e. phenylacetic acid formed under the effect of the enzyme. The determination was performed on a chromatograph. The immobile phase consisted of 10 per cent of ethylenglycol edipate on chromosorb A, modified with 2 per cent H3PO4. Nitrogen was used as the gaseous carrier. The method is rapid and handy for mass testing of the cultures with a purpose of detecting penicillinacylase-producing strains. It provided reliable determination of penicillinacylase in the cultures producing simultaneously beta-lactamase, another penicillin-destroying enzyme.", "contents": "[Determination of the penicillin acylase activity of E. coli cultures using a method of gas-liquid chromatography]. Penicillinacylase activity was determined in E. coli by the product of benzylpenicillin destruction, i.e. phenylacetic acid formed under the effect of the enzyme. The determination was performed on a chromatograph. The immobile phase consisted of 10 per cent of ethylenglycol edipate on chromosorb A, modified with 2 per cent H3PO4. Nitrogen was used as the gaseous carrier. The method is rapid and handy for mass testing of the cultures with a purpose of detecting penicillinacylase-producing strains. It provided reliable determination of penicillinacylase in the cultures producing simultaneously beta-lactamase, another penicillin-destroying enzyme."} {"id": "PMID:170854", "title": "[Rifampicin effectiveness in experimental anaerobic gas infection].", "content": "The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time.", "contents": "[Rifampicin effectiveness in experimental anaerobic gas infection]. The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time."} {"id": "PMID:170855", "title": "Bactericidal activity of superoxide anion and of hydrogen peroxide: investigations employing dialuric acid, a superoxide-generating drug.", "content": "The addition of dialuric acid (a superoxide-generating drug) to a suspension of resting human neutrophils resulted in a stimulation of cellular hexose monophosphate shunt activity. Measurement of oxygen consumption demonstrated a rapid rate of oxygen uptake by the drug alone in aqueous solution. The subsequent addition of catalase (but not of superoxide dismutase) resulted in a substantial release of oxygen, indicating that H(2)O(2) was accumulating in the media. The generation of O(2) (-) by the drug was verified by measuring the rate of reduction of cytochrome c by the drug in the presence and absence of authentic superoxide dismutase. The growth of Escherichia coli B and Staphylococcus aureus was inhibited in vitro by addition of the drug to a suitable culture media; the degree of inhibition was dose dependent. This inhibition of bacterial growth could be completely reversed by the addition of as little as 5 mug of purified catalase, but was not affected by concentrations of superoxide dismutase that were 2,000-fold higher. These results suggest that the dialuric acid-induced stimulation of hexose monophosphate shunt activity in neutrophils is due to accumulated H(2)O(2). Further, the contribution of superoxide to the bactericidal activity towards E. coli and S. aureus is probably minimal compared with that of H(2)O(2).", "contents": "Bactericidal activity of superoxide anion and of hydrogen peroxide: investigations employing dialuric acid, a superoxide-generating drug. The addition of dialuric acid (a superoxide-generating drug) to a suspension of resting human neutrophils resulted in a stimulation of cellular hexose monophosphate shunt activity. Measurement of oxygen consumption demonstrated a rapid rate of oxygen uptake by the drug alone in aqueous solution. The subsequent addition of catalase (but not of superoxide dismutase) resulted in a substantial release of oxygen, indicating that H(2)O(2) was accumulating in the media. The generation of O(2) (-) by the drug was verified by measuring the rate of reduction of cytochrome c by the drug in the presence and absence of authentic superoxide dismutase. The growth of Escherichia coli B and Staphylococcus aureus was inhibited in vitro by addition of the drug to a suitable culture media; the degree of inhibition was dose dependent. This inhibition of bacterial growth could be completely reversed by the addition of as little as 5 mug of purified catalase, but was not affected by concentrations of superoxide dismutase that were 2,000-fold higher. These results suggest that the dialuric acid-induced stimulation of hexose monophosphate shunt activity in neutrophils is due to accumulated H(2)O(2). Further, the contribution of superoxide to the bactericidal activity towards E. coli and S. aureus is probably minimal compared with that of H(2)O(2)."} {"id": "PMID:170856", "title": "Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro.", "content": "A newly described 6beta-amidinopenicillanic acid derivative, mecillinam (formerly called FL 1060), showed a high in vitro activity against Enterobacteriaceae. The effect on Escherichia coli was bactericidal and was due to lysis of the cells. The longer the culture grew under the influence of mecillinam or the lower the inoculum, the greater the bactericidal effect. The morphology of the cells changed towards large spheric forms (2 to 5 mum) under the influence of mecillinam. Consequently a great discrepancy between the optical density and the viable count was seen. The morphologically abnormal cells could be protected against lysis in vitro by addition of ionized compounds such as sodium chloride. Abnormal cells were more sensitive to ampicillin than normal cells. As expected synergy could be demonstrated between mecillinam and ampicillin. This was marked under experimental conditions where the abnormal cells were protected against lysis.", "contents": "Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro. A newly described 6beta-amidinopenicillanic acid derivative, mecillinam (formerly called FL 1060), showed a high in vitro activity against Enterobacteriaceae. The effect on Escherichia coli was bactericidal and was due to lysis of the cells. The longer the culture grew under the influence of mecillinam or the lower the inoculum, the greater the bactericidal effect. The morphology of the cells changed towards large spheric forms (2 to 5 mum) under the influence of mecillinam. Consequently a great discrepancy between the optical density and the viable count was seen. The morphologically abnormal cells could be protected against lysis in vitro by addition of ionized compounds such as sodium chloride. Abnormal cells were more sensitive to ampicillin than normal cells. As expected synergy could be demonstrated between mecillinam and ampicillin. This was marked under experimental conditions where the abnormal cells were protected against lysis."} {"id": "PMID:170857", "title": "Mode of action of polymyxin B: physiological studies with Bacillus subtilis-resistant mutant.", "content": "Polymyxin B resistance in Bacillus subtilis can be suppressed by the synergistic action of lysozyme or of an analogous cell wall lytic activity released by B. subtilis spores during germination. Such a synergistic effect is probably due to partial cell-wall digestion by lysozyme that allows polymyxin to reach its site of action and is therefore distinct from the analogous synergistic effect described by other authors in Escherichia coli. In the latter case polymyxin B probably damaged the outer membrane, allowing lysozyme to reach and digest the cell wall.", "contents": "Mode of action of polymyxin B: physiological studies with Bacillus subtilis-resistant mutant. Polymyxin B resistance in Bacillus subtilis can be suppressed by the synergistic action of lysozyme or of an analogous cell wall lytic activity released by B. subtilis spores during germination. Such a synergistic effect is probably due to partial cell-wall digestion by lysozyme that allows polymyxin to reach its site of action and is therefore distinct from the analogous synergistic effect described by other authors in Escherichia coli. In the latter case polymyxin B probably damaged the outer membrane, allowing lysozyme to reach and digest the cell wall."} {"id": "PMID:170858", "title": "Irreversible inhibition of herpes simplex virus replication in BSC-1 cells by zinc ions.", "content": "Zinc sulfate added to the medium of herpes simplex virus-infected BSC-1 cells, at a concentration of 0.1 mM, inhibited the synthesis of infectious virus progeny by 95 to 96%. A concentration of 0.2 mM zinc sulfate inhibited herpes simplex virus synthesis by 99.8% as determined by centrifugation in sucrose gradients and by plaque assay on BSC-1 monolayers. The inhibition of herpes simplex virus replication in BSC-1 cells was found to be irreversible.", "contents": "Irreversible inhibition of herpes simplex virus replication in BSC-1 cells by zinc ions. Zinc sulfate added to the medium of herpes simplex virus-infected BSC-1 cells, at a concentration of 0.1 mM, inhibited the synthesis of infectious virus progeny by 95 to 96%. A concentration of 0.2 mM zinc sulfate inhibited herpes simplex virus synthesis by 99.8% as determined by centrifugation in sucrose gradients and by plaque assay on BSC-1 monolayers. The inhibition of herpes simplex virus replication in BSC-1 cells was found to be irreversible."} {"id": "PMID:170859", "title": "Detection of animal viruses in coastal seawater and sediments.", "content": "Animal viruses, predominantly enteroviruses, were detected in shallow water at bottom depths and in clastic marine sediments. Viruses accumulated in sandy and slimy deposits of the sea bottom near the shore and could be easily released into water by means of simple mechanical shaking.", "contents": "Detection of animal viruses in coastal seawater and sediments. Animal viruses, predominantly enteroviruses, were detected in shallow water at bottom depths and in clastic marine sediments. Viruses accumulated in sandy and slimy deposits of the sea bottom near the shore and could be easily released into water by means of simple mechanical shaking."} {"id": "PMID:170870", "title": "Eczema herpeticum. Treatment with methylene blue and light.", "content": "Kaposi varicelliform eruption due to herpes simplex virus (eczema herpeticum) is a serious disease in infants, with occasional fatal outcome. Photoinactivation therapy consisting of local application of methylene blue followed by light exposure resulted in rapid improvement both clinically and virologically. Methylene blue, at a concentration of 10(-5)M was found to be viricidal to herpesvirus in the light but not in the dark.", "contents": "Eczema herpeticum. Treatment with methylene blue and light. Kaposi varicelliform eruption due to herpes simplex virus (eczema herpeticum) is a serious disease in infants, with occasional fatal outcome. Photoinactivation therapy consisting of local application of methylene blue followed by light exposure resulted in rapid improvement both clinically and virologically. Methylene blue, at a concentration of 10(-5)M was found to be viricidal to herpesvirus in the light but not in the dark."} {"id": "PMID:170871", "title": "Failure of laboratory and radiological studies to predict jejunal mucosal atrophy.", "content": "Of 58 children with suspected malabsorption, 27 were shown to have subtotal or partial atrophy, and 31 had normal mucosal histology. Oral glucose tolerance tests, faecal fat excretion, D-xylose excretion tests, Prosparol absorption studies, haematological investigations, and radiological examination of the small bowel failed to distinguish these two groups and frequently gave misleading results. It is concluded that in suspected coeliac disease small intestinal biopsy should be performed as a primary investigation.", "contents": "Failure of laboratory and radiological studies to predict jejunal mucosal atrophy. Of 58 children with suspected malabsorption, 27 were shown to have subtotal or partial atrophy, and 31 had normal mucosal histology. Oral glucose tolerance tests, faecal fat excretion, D-xylose excretion tests, Prosparol absorption studies, haematological investigations, and radiological examination of the small bowel failed to distinguish these two groups and frequently gave misleading results. It is concluded that in suspected coeliac disease small intestinal biopsy should be performed as a primary investigation."} {"id": "PMID:170872", "title": "Nitrogen dioxide and the erythrocyte redox state.", "content": "Normal human erythrocytes were exposed for two hours at 38 C to an atmosphere of air containing variable concentrations of nitrogen dioxide, in order to detect any primary cytoplasmic effect of NO2 on the calculated oxidation-reduction (redox) ratio ([NAD+]/[NADH]) of a mitochondria-free cell. Substantial increases in the redox ratio were noted only when NO2 concentrations exceeded 15 ppm. In the range of 15 to 500 ppm NO2, the increase in the redox ratio significantly correlated with the NO2 concentration (r=.71; p less than .01). Intracellular to extracellular anion distribution ratios for chloride, lactate, and pyruvate were similar in NO2 and non-NO2 exposed cells, suggesting absence of a substantial hemolytic effect. These data identify a direct cytoplasmic NO2-induced biochemical change that may be mediated by a mechanism other than lipid peroxidation. Alteration of hemoglobin or NAD-NADH-dependent enzyme activity is suggested.", "contents": "Nitrogen dioxide and the erythrocyte redox state. Normal human erythrocytes were exposed for two hours at 38 C to an atmosphere of air containing variable concentrations of nitrogen dioxide, in order to detect any primary cytoplasmic effect of NO2 on the calculated oxidation-reduction (redox) ratio ([NAD+]/[NADH]) of a mitochondria-free cell. Substantial increases in the redox ratio were noted only when NO2 concentrations exceeded 15 ppm. In the range of 15 to 500 ppm NO2, the increase in the redox ratio significantly correlated with the NO2 concentration (r=.71; p less than .01). Intracellular to extracellular anion distribution ratios for chloride, lactate, and pyruvate were similar in NO2 and non-NO2 exposed cells, suggesting absence of a substantial hemolytic effect. These data identify a direct cytoplasmic NO2-induced biochemical change that may be mediated by a mechanism other than lipid peroxidation. Alteration of hemoglobin or NAD-NADH-dependent enzyme activity is suggested."} {"id": "PMID:170875", "title": "[14 cases of constrictive endocardial fibrosis (or endomyocardial fibrosis].", "content": "Constrictive endocardial fibrosis (CEF) or endomyocardial fibrosis (EMF) was studied on 14 files of this rather frequent disease in Ivory Coast. On the basis of the data derived from angiocardiography, catheterization and mechanograms, the clinical signs are interpreted better. Thus one is able to describe with accuracy some clinical forms, the commonest of which being a right heart restriction combined with left-sided signs. It seems important underline how useful the external pulse recordings might be useful for the diagnosis in view of their analogy with the pressure curves. In this disease with a severe course, bold surgical treatments provide some hope. On the contrary, its aetiology remains mysterious. Our best landmark being the link of CEP with tropical ecology, and in particular, in our cases, with the warm and damp forest ecology of some areas.", "contents": "[14 cases of constrictive endocardial fibrosis (or endomyocardial fibrosis]. Constrictive endocardial fibrosis (CEF) or endomyocardial fibrosis (EMF) was studied on 14 files of this rather frequent disease in Ivory Coast. On the basis of the data derived from angiocardiography, catheterization and mechanograms, the clinical signs are interpreted better. Thus one is able to describe with accuracy some clinical forms, the commonest of which being a right heart restriction combined with left-sided signs. It seems important underline how useful the external pulse recordings might be useful for the diagnosis in view of their analogy with the pressure curves. In this disease with a severe course, bold surgical treatments provide some hope. On the contrary, its aetiology remains mysterious. Our best landmark being the link of CEP with tropical ecology, and in particular, in our cases, with the warm and damp forest ecology of some areas."} {"id": "PMID:170877", "title": "[Neonatal hypoglycemia due to hyperinsulinism secondary to Langerhans' polyadenomatosis. Recovery after pancreatectomy].", "content": "Report of a case of a neonatal hypoglycemia detected at the 11th hour of life, secondary to a Langherans polyadenomatosis in a girl with an hemihypertrophy. Pre- and post-operative tests are reported. In case of neonatal hypoglycemia, the criteria leading to the diagnosis of hyperinsulinism, i.e. the only neonatal hypoglycemia with surgical treatment are reviewed. Except in the case of adenoma, the pancreatectomy should be performed subtotally. The best time for surgery is as soon as the 3rd week, in order to preserve the cerebral development.", "contents": "[Neonatal hypoglycemia due to hyperinsulinism secondary to Langerhans' polyadenomatosis. Recovery after pancreatectomy]. Report of a case of a neonatal hypoglycemia detected at the 11th hour of life, secondary to a Langherans polyadenomatosis in a girl with an hemihypertrophy. Pre- and post-operative tests are reported. In case of neonatal hypoglycemia, the criteria leading to the diagnosis of hyperinsulinism, i.e. the only neonatal hypoglycemia with surgical treatment are reviewed. Except in the case of adenoma, the pancreatectomy should be performed subtotally. The best time for surgery is as soon as the 3rd week, in order to preserve the cerebral development."} {"id": "PMID:170882", "title": "[A transplantable myeloid hamster leukemia with high peripheral leukocyte counts and C-particles. II. Histology and cytochemistry (author's transl)].", "content": "Results on morphologic and hematologic characterization of a hamster leukemia capable of both cellular and cellfree transmission are described. Solid tumors removed in the course of several passages of leukemia animals, after producing blood smears, and spleen, liver, lymph nodes, bone marrow, thymus, kidney and lung were investigated histologically and histochemically. The morphological picture of the hamster leukemia has not changed during several transplantation generations. In addition to solid tumours, typical leukemic infiltration were detected histologically in spleen, liver, lymph nodes, bone marrow, kidneys and lung. No leukemic proliferation was noticed in the thymus. The final stage of the disease is characterized by an abrupt occurrence of high leukemic cell counts. The demonstration of alkaline phosphatase, but especially of naphtol-AS-D-chloroacetate esterase, in the leukemic cells is interpreted as indicating malignization of cells of the granulocytic line.", "contents": "[A transplantable myeloid hamster leukemia with high peripheral leukocyte counts and C-particles. II. Histology and cytochemistry (author's transl)]. Results on morphologic and hematologic characterization of a hamster leukemia capable of both cellular and cellfree transmission are described. Solid tumors removed in the course of several passages of leukemia animals, after producing blood smears, and spleen, liver, lymph nodes, bone marrow, thymus, kidney and lung were investigated histologically and histochemically. The morphological picture of the hamster leukemia has not changed during several transplantation generations. In addition to solid tumours, typical leukemic infiltration were detected histologically in spleen, liver, lymph nodes, bone marrow, kidneys and lung. No leukemic proliferation was noticed in the thymus. The final stage of the disease is characterized by an abrupt occurrence of high leukemic cell counts. The demonstration of alkaline phosphatase, but especially of naphtol-AS-D-chloroacetate esterase, in the leukemic cells is interpreted as indicating malignization of cells of the granulocytic line."} {"id": "PMID:170883", "title": "Growth inhibition of sarcoma 180 induced by silica and talc.", "content": "In applying amorphous silica and talc in the site of solid Sarcoma 180 implants, the authors found a suppression and delay of tumor growth which was proveked by peritumoral foreign-body granulomas. Correlating these findings which those experiments which resulted in granulomas of hypersensitivity type, it may be suggested that any kind of peritumoral chronic inflammation enables an anti-tumor effect.", "contents": "Growth inhibition of sarcoma 180 induced by silica and talc. In applying amorphous silica and talc in the site of solid Sarcoma 180 implants, the authors found a suppression and delay of tumor growth which was proveked by peritumoral foreign-body granulomas. Correlating these findings which those experiments which resulted in granulomas of hypersensitivity type, it may be suggested that any kind of peritumoral chronic inflammation enables an anti-tumor effect."} {"id": "PMID:170884", "title": "[Alcoholic polyneuropathy. Electrophysiological and clinical findings in 85 patients (author's transl)].", "content": "Maximum motor and sensory nerve conduction velocities, amplitudes of muscle action potentials (surface electrodes) and of sensory nerve action potentials, and needle electromyograms were studied in 80 patients with alcoholic neuropathy and in 5 chronic alcoholics without clinical signs of neuropathy. The electrophysiological results were compared to the clinical findings. Neurographic criteria compatible with the diagnosis \"alcoholic neuropathy\" were defined. Neurographic findings contrary to a diagnosis of alcoholic etiology were demonstrated in 3 patients. Only in a smaller group of patients could a reduction of conduction velocity be found, especially in regions of peripheral nerve entrapment. A decrease in conduction velocity outside of the entrapment sites can be explained in some cases by segmental demyelination in chronic hepatitis or cirrhosis of the liver.", "contents": "[Alcoholic polyneuropathy. Electrophysiological and clinical findings in 85 patients (author's transl)]. Maximum motor and sensory nerve conduction velocities, amplitudes of muscle action potentials (surface electrodes) and of sensory nerve action potentials, and needle electromyograms were studied in 80 patients with alcoholic neuropathy and in 5 chronic alcoholics without clinical signs of neuropathy. The electrophysiological results were compared to the clinical findings. Neurographic criteria compatible with the diagnosis \"alcoholic neuropathy\" were defined. Neurographic findings contrary to a diagnosis of alcoholic etiology were demonstrated in 3 patients. Only in a smaller group of patients could a reduction of conduction velocity be found, especially in regions of peripheral nerve entrapment. A decrease in conduction velocity outside of the entrapment sites can be explained in some cases by segmental demyelination in chronic hepatitis or cirrhosis of the liver."} {"id": "PMID:170885", "title": "Immunoglobulins and their relative neutralizing efficiency in cattle immunized with infectious bovine rhinotracheitis--parainfluenza-3 (IBR-PI-3) virus vaccine.", "content": "The localization of anti-IBR and anti-PI-3 activity in the serum and nasal secretory immunoglobulins following intranasal immunization of cattle with a mixed vaccine (IBR-PI-3, MLV, TCO) was studied and was found to reside in the nasal secretory IgA, serum IgM and IgG fractions. The computation of their relative virus neutralizing efficiencies from kinetic data revealed their order of neutralizing efficiencies to be IgM greater than IgA greather than IgG.", "contents": "Immunoglobulins and their relative neutralizing efficiency in cattle immunized with infectious bovine rhinotracheitis--parainfluenza-3 (IBR-PI-3) virus vaccine. The localization of anti-IBR and anti-PI-3 activity in the serum and nasal secretory immunoglobulins following intranasal immunization of cattle with a mixed vaccine (IBR-PI-3, MLV, TCO) was studied and was found to reside in the nasal secretory IgA, serum IgM and IgG fractions. The computation of their relative virus neutralizing efficiencies from kinetic data revealed their order of neutralizing efficiencies to be IgM greater than IgA greather than IgG."} {"id": "PMID:170879", "title": "[Hepatic amebiasis in an infant].", "content": "Case report of a 8 month-old North-African infant with liver amebiasis. This disease is not rare in young children and may be observed in all endemic zones of amebiasis. The clinical characteristics, special for the age, and the biological features are reviewed. The diagnosis relies on immunological tests. Treatment is essentially medical, metronidazole often being effective.", "contents": "[Hepatic amebiasis in an infant]. Case report of a 8 month-old North-African infant with liver amebiasis. This disease is not rare in young children and may be observed in all endemic zones of amebiasis. The clinical characteristics, special for the age, and the biological features are reviewed. The diagnosis relies on immunological tests. Treatment is essentially medical, metronidazole often being effective."} {"id": "PMID:170886", "title": "[Sensitivity of various primate cells and animal viruses to the antiviral activity of human leukocyte interferon (author's transl)].", "content": "U cells (a permanent, human amnion cell line) were protected against infection with Semliki Forest Virus (SFV) by human interferon (HIF) from peripheral leukocytes. Despite the usual genus-specific action of interferons, mouse L929 cultures (a permanent mouse fibroblast cell line) were also protected by HIF. The antiviral action of HIF in six other primate cell cultures was also examined. It is of interest that two lymphoblastoid cell lines, RPMI1788 and Kaplan, were insensitive to HIF. The sensitivity of ten different viruses against HIF in primary African green monkey kidney cell cultures was compared. Among the viruses tested SFV was the most sensitive whereas two strains of vaccinia virus were barely inhibited. In contrast, type 1 herpes simplex virus was relatively sensitive to the action of HIF.", "contents": "[Sensitivity of various primate cells and animal viruses to the antiviral activity of human leukocyte interferon (author's transl)]. U cells (a permanent, human amnion cell line) were protected against infection with Semliki Forest Virus (SFV) by human interferon (HIF) from peripheral leukocytes. Despite the usual genus-specific action of interferons, mouse L929 cultures (a permanent mouse fibroblast cell line) were also protected by HIF. The antiviral action of HIF in six other primate cell cultures was also examined. It is of interest that two lymphoblastoid cell lines, RPMI1788 and Kaplan, were insensitive to HIF. The sensitivity of ten different viruses against HIF in primary African green monkey kidney cell cultures was compared. Among the viruses tested SFV was the most sensitive whereas two strains of vaccinia virus were barely inhibited. In contrast, type 1 herpes simplex virus was relatively sensitive to the action of HIF."} {"id": "PMID:170878", "title": "[Hypophyseal gonadotropin secretion in sexual precocity with McCune-Albright's syndrome].", "content": "In three young girls with isosexual precocity and fibrous dysplasia of bones, plasma gonadotropins (LH and FSH) response to releasing hormone (LH-RH) has been much under the mean response in true female precocious puberty. These data and those previously reported in the literature suggest that MacCune-Albright's syndrome correlates to an hypothalamo-pituitary dysfunction rather than to a true prematurity.", "contents": "[Hypophyseal gonadotropin secretion in sexual precocity with McCune-Albright's syndrome]. In three young girls with isosexual precocity and fibrous dysplasia of bones, plasma gonadotropins (LH and FSH) response to releasing hormone (LH-RH) has been much under the mean response in true female precocious puberty. These data and those previously reported in the literature suggest that MacCune-Albright's syndrome correlates to an hypothalamo-pituitary dysfunction rather than to a true prematurity."} {"id": "PMID:170888", "title": "Structural and growth characteristics of two avian reoviruses.", "content": "Two virus strains which had been suspected to be the etiological agents of infectious bursitis (Gumboro disease) and of inclusion body hepatitis of chickens were characterized by their morphology, their peptide composition and the segmented genome of their double-stranded RNA to be typical reoviruses. Although the 2 avian strains did not clearly differ in their serological behaviour, the size of some of their RNA segments were not identical. Both strains replicated in tissue cultures prepared from the chorioallantoic membrane of embryonated eggs with growth characteristics of reoviruses.", "contents": "Structural and growth characteristics of two avian reoviruses. Two virus strains which had been suspected to be the etiological agents of infectious bursitis (Gumboro disease) and of inclusion body hepatitis of chickens were characterized by their morphology, their peptide composition and the segmented genome of their double-stranded RNA to be typical reoviruses. Although the 2 avian strains did not clearly differ in their serological behaviour, the size of some of their RNA segments were not identical. Both strains replicated in tissue cultures prepared from the chorioallantoic membrane of embryonated eggs with growth characteristics of reoviruses."} {"id": "PMID:170891", "title": "[Ultrastructure of human hepatocytes in early prenatal ontogenesis].", "content": "The structure of hepatic cells was studied in 40 human embryos and fetuses from 4 to 16 weeks of intrauterine development. Depending on the differentiation degree of organells and their amount in the hepatic cell of the embryo and fetus three types of hepatic cells are distinguished: slightly differentiated, transitional and differentiated cells. In the course of early prenatal ontogenesis the amount of slightly differentiated hepatic cells diminishes and the amount of transitional and differentiated forms increases. Glycogen granules are found in the embryo hepatic cells from 7-8 weeks of intrauterine development, and in the course of further embryonic development one can speak of establishment of the protein-forming function of the liver on the basis of increased amount of elements of the endoplasmic network and the presence of numerous ribosomes and polysomes in the cell. The hepatic cells of 14-16 week embryos have well pronounced sinusoid and biliar poles.", "contents": "[Ultrastructure of human hepatocytes in early prenatal ontogenesis]. The structure of hepatic cells was studied in 40 human embryos and fetuses from 4 to 16 weeks of intrauterine development. Depending on the differentiation degree of organells and their amount in the hepatic cell of the embryo and fetus three types of hepatic cells are distinguished: slightly differentiated, transitional and differentiated cells. In the course of early prenatal ontogenesis the amount of slightly differentiated hepatic cells diminishes and the amount of transitional and differentiated forms increases. Glycogen granules are found in the embryo hepatic cells from 7-8 weeks of intrauterine development, and in the course of further embryonic development one can speak of establishment of the protein-forming function of the liver on the basis of increased amount of elements of the endoplasmic network and the presence of numerous ribosomes and polysomes in the cell. The hepatic cells of 14-16 week embryos have well pronounced sinusoid and biliar poles."} {"id": "PMID:170892", "title": "[Dark and light neurons in the cortical plate of the forebrain of the swamp turtle].", "content": "Electron microscopic study of the neuronal composition of Emys orbicularis cortical zones as compared with the light microscopy data has revealed that the distinctions in the cell cytoplasm ultrastructure with respect to the dendrite branching pattern and the peculiarities of their localization in the cortical plate are suggestive of a possible metabolic heterogeneity and can serve as a foundation of the morpho-functional characteristics of the neurons. A few neuronal types of neurons have been revealed: 1. light neurons distinguished by the cytoplasm matrix devoid of any electron density, a poorly developed endoplasmic reticulum and a few cytoplasmatic organells and inclusions; 2. light neurons having slight osmophility of the cytoplasm matrix, a more developed endoplasmic reticulum with elongated cisternae, a great number of organells including neurofilaments; 3. dark neurons having a high degree of cytoplasm matrix and the nucleus, a large number of the nuclei, cytoplasm, dendrites and axons in contrast to the above described patterns.", "contents": "[Dark and light neurons in the cortical plate of the forebrain of the swamp turtle]. Electron microscopic study of the neuronal composition of Emys orbicularis cortical zones as compared with the light microscopy data has revealed that the distinctions in the cell cytoplasm ultrastructure with respect to the dendrite branching pattern and the peculiarities of their localization in the cortical plate are suggestive of a possible metabolic heterogeneity and can serve as a foundation of the morpho-functional characteristics of the neurons. A few neuronal types of neurons have been revealed: 1. light neurons distinguished by the cytoplasm matrix devoid of any electron density, a poorly developed endoplasmic reticulum and a few cytoplasmatic organells and inclusions; 2. light neurons having slight osmophility of the cytoplasm matrix, a more developed endoplasmic reticulum with elongated cisternae, a great number of organells including neurofilaments; 3. dark neurons having a high degree of cytoplasm matrix and the nucleus, a large number of the nuclei, cytoplasm, dendrites and axons in contrast to the above described patterns."} {"id": "PMID:170893", "title": "[Ultrastructure of experimental virus-induced hemangiopericytomas].", "content": "Electron-microscopy studies of malignant low-differentiated hemangiopericytomas, induced by adenovirus of monkeys SA7(C8) and bovine adenovirus type 3 were, carried out. At earlier stages of the development of these tumours in tumourous cells located around capillaries there were observed the ultrastructural characteristics typical of pericytes and cells of human hemangiopericytis: the presence of the basal layer and fibrills as thick as 40 A. As differentiation proceeded, tumorous cells acquired an elongated form, and in some of them there appeared myofilaments typical of smooth-muscle cells, with local thickenings, as well as multitude of pinicytic vacules along the plasmatic membranes of cells. The foregoing confirms the assumption of hemangiopericytomas as a prestage of leio-(angioleio-) myosarcomas. Moreover, the tumour cells revealed the presence of cilia, fibrills as thick as 100A, 75A, annulate lamelae, and myelin-like formations.", "contents": "[Ultrastructure of experimental virus-induced hemangiopericytomas]. Electron-microscopy studies of malignant low-differentiated hemangiopericytomas, induced by adenovirus of monkeys SA7(C8) and bovine adenovirus type 3 were, carried out. At earlier stages of the development of these tumours in tumourous cells located around capillaries there were observed the ultrastructural characteristics typical of pericytes and cells of human hemangiopericytis: the presence of the basal layer and fibrills as thick as 40 A. As differentiation proceeded, tumorous cells acquired an elongated form, and in some of them there appeared myofilaments typical of smooth-muscle cells, with local thickenings, as well as multitude of pinicytic vacules along the plasmatic membranes of cells. The foregoing confirms the assumption of hemangiopericytomas as a prestage of leio-(angioleio-) myosarcomas. Moreover, the tumour cells revealed the presence of cilia, fibrills as thick as 100A, 75A, annulate lamelae, and myelin-like formations."} {"id": "PMID:170894", "title": "[Basal cell adenomas of the salivary glands].", "content": "The author presents data on morphology and clinical features of basal-cell adenomas of the salivary gland (10 cases). Singling out this neoplasm into independent onconosological group seems reasonable since basal-cell adenoma not infrequently is erroneously diagnosed as cylindroma or mixed tumour of the salivary gland, which may lead to a wrong clinical prognosis and inadequate therapeutic measures. The clinical course of this tumour is benign. The main morphological feature of the tumour is a monomorphic character of cell elements, their palisade-like distribution over the periphery of individual tumour structures and a clear-cut delimination of the parenchyma from the stroma.", "contents": "[Basal cell adenomas of the salivary glands]. The author presents data on morphology and clinical features of basal-cell adenomas of the salivary gland (10 cases). Singling out this neoplasm into independent onconosological group seems reasonable since basal-cell adenoma not infrequently is erroneously diagnosed as cylindroma or mixed tumour of the salivary gland, which may lead to a wrong clinical prognosis and inadequate therapeutic measures. The clinical course of this tumour is benign. The main morphological feature of the tumour is a monomorphic character of cell elements, their palisade-like distribution over the periphery of individual tumour structures and a clear-cut delimination of the parenchyma from the stroma."} {"id": "PMID:170895", "title": "[Basophilic adenoma in combination with a prolapse of adenohypophyseal tissue through the capsule].", "content": "During the post-mortem examination of a 15-year patient who had died after the operation connected with incision of commissures a distorted form of the hypophysis was noted. Histological, histochemical and morphometric investigations showed that there was basophilic adenoma of adenohypophysis and prolapse of the tissue (beyond the borders of the adenoma) through a fistula against the background of changes characteristic of chronic diseases in childhood. Oxyphilic shift, moreover, was noted not only in the first zone of the adenohypophysis, but in other zones, as well as with a simultaneous increase in number of basophiles in I--III zones. Prolapse of the tissue, the latter being normal as far as the tumours growth was concerned, through the fistula took place at a considerable distance from the adenoma, which justifies the consideration of this process as a result of hyperplasia not connected with adenoma. Edges of the fistula bordering the prolapse, haemorrhages were to be seen.", "contents": "[Basophilic adenoma in combination with a prolapse of adenohypophyseal tissue through the capsule]. During the post-mortem examination of a 15-year patient who had died after the operation connected with incision of commissures a distorted form of the hypophysis was noted. Histological, histochemical and morphometric investigations showed that there was basophilic adenoma of adenohypophysis and prolapse of the tissue (beyond the borders of the adenoma) through a fistula against the background of changes characteristic of chronic diseases in childhood. Oxyphilic shift, moreover, was noted not only in the first zone of the adenohypophysis, but in other zones, as well as with a simultaneous increase in number of basophiles in I--III zones. Prolapse of the tissue, the latter being normal as far as the tumours growth was concerned, through the fistula took place at a considerable distance from the adenoma, which justifies the consideration of this process as a result of hyperplasia not connected with adenoma. Edges of the fistula bordering the prolapse, haemorrhages were to be seen."} {"id": "PMID:170899", "title": "Treatment of Cataplexy with Clomipramine.", "content": "A new antodepressant drug, clomipramine hydrochloride, closely related to imipramine hydrochloride, was used to treat four patients suffering from cataplexy, sleep paralysis, and hypnagogic hallucinations. Attacks of cataplexy were associated with rapid-eye-movement (REM) electroencephalographic patterns. Cloripramine, in doses of 25 to 75 mg/day, completely stopped all attacks of cataplexy, sleep paralysis, and hypnagogic hallucinations within 48 hours of initial therapy. The patients have been free of symptoms for periods of 10 to 21 months. Side effects included impotence in the male patients, but no hematologic, cardiovascular, hepatic, or renal toxic effects were observed. Available evidence suggests that such drugs inhibit those brain stem systems that control the toxic components of REM sleep.", "contents": "Treatment of Cataplexy with Clomipramine. A new antodepressant drug, clomipramine hydrochloride, closely related to imipramine hydrochloride, was used to treat four patients suffering from cataplexy, sleep paralysis, and hypnagogic hallucinations. Attacks of cataplexy were associated with rapid-eye-movement (REM) electroencephalographic patterns. Cloripramine, in doses of 25 to 75 mg/day, completely stopped all attacks of cataplexy, sleep paralysis, and hypnagogic hallucinations within 48 hours of initial therapy. The patients have been free of symptoms for periods of 10 to 21 months. Side effects included impotence in the male patients, but no hematologic, cardiovascular, hepatic, or renal toxic effects were observed. Available evidence suggests that such drugs inhibit those brain stem systems that control the toxic components of REM sleep."} {"id": "PMID:170902", "title": "The influence of some fractions of egg yolk on the survival of ram spermatozoa at 5 degrees C.", "content": "Ram spermatozoa were stored at 5 degrees C in diluents containing various fractions of egg yolk prepared by dialysis, ultrafiltration and ion-exchange chromatography. They survived storage best in the presence of components of egg yolk which were non-dialysable and were not filtered through membranes which retained substances of molecular weight greater than 100 000. The substances isolated in peak B of the ion-exchange chromatogram of whole egg yolk described by Seideman et al. (1969) gave greater protection than those from other fractions from this chromatographic system. These data indicate that the low-density lipoprotein fraction of egg yolk is the most likely source of protection to ram spermatozoa against the effects of storage at 5 degrees C.", "contents": "The influence of some fractions of egg yolk on the survival of ram spermatozoa at 5 degrees C. Ram spermatozoa were stored at 5 degrees C in diluents containing various fractions of egg yolk prepared by dialysis, ultrafiltration and ion-exchange chromatography. They survived storage best in the presence of components of egg yolk which were non-dialysable and were not filtered through membranes which retained substances of molecular weight greater than 100 000. The substances isolated in peak B of the ion-exchange chromatogram of whole egg yolk described by Seideman et al. (1969) gave greater protection than those from other fractions from this chromatographic system. These data indicate that the low-density lipoprotein fraction of egg yolk is the most likely source of protection to ram spermatozoa against the effects of storage at 5 degrees C."} {"id": "PMID:170903", "title": "Pyridine nucleosidase in bull semen I. Breed and sire differences in enzyme concentration.", "content": "The concentration of pyridine nucleosidase which cleaves the nicotinamide-ribose bond in NAD and related compounds was assayed using the cyanide addition reaction in semen samples collected by artificial vagina from 246 bulls. Among the 205 sires of recognized dairy breeds the nucleosidase concentration ranged from 0 to 1470 units/ml semen. Of the dairy sires 18% produced semen containing no nucleosidase activity. Among the 41 sires of recognized beef breeds 54% had no nucleosidase and the highest concentration was 630 units/ml semen. Among 20 sires from each of which 5-17 collections were assayed, there were significant differences in average nucleosidase concentration. There was a discontinuous distribution in nucleosidase concentration among the 169 dairy sires producing semen with measurable enzyme activity. Results for 18 dairy sires each with from 4 to 16 sons showed that sires with no seminal nucleosidase produced more sons with no enzyme or lower concentrations of enzyme than sires with higher nucleosidase concentrations. It is suggested that the concentration of the nucleosidase in bull semen is simply inherited.", "contents": "Pyridine nucleosidase in bull semen I. Breed and sire differences in enzyme concentration. The concentration of pyridine nucleosidase which cleaves the nicotinamide-ribose bond in NAD and related compounds was assayed using the cyanide addition reaction in semen samples collected by artificial vagina from 246 bulls. Among the 205 sires of recognized dairy breeds the nucleosidase concentration ranged from 0 to 1470 units/ml semen. Of the dairy sires 18% produced semen containing no nucleosidase activity. Among the 41 sires of recognized beef breeds 54% had no nucleosidase and the highest concentration was 630 units/ml semen. Among 20 sires from each of which 5-17 collections were assayed, there were significant differences in average nucleosidase concentration. There was a discontinuous distribution in nucleosidase concentration among the 169 dairy sires producing semen with measurable enzyme activity. Results for 18 dairy sires each with from 4 to 16 sons showed that sires with no seminal nucleosidase produced more sons with no enzyme or lower concentrations of enzyme than sires with higher nucleosidase concentrations. It is suggested that the concentration of the nucleosidase in bull semen is simply inherited."} {"id": "PMID:170904", "title": "Mitochondrial changes, ion and water shifts in the cellular injury of ehrlich ascites tumor cells.", "content": "Cellular injury was produced in Ehlrich ascites tumor cells by an inhibitor of the function of the cell membrane [10(-3M) parachloromercuribenzenesulfonic acid (PCMBS)] or by inhibitors of respiration (10(-4M) Antimycin A), glycolysis (10(-4M), iodoacetic acid, IAA), oxidative phosphorylation (10(-3M) 2,4 dinitrophenol, DNP) or by combinations of these in a medium with or without glucose. The contents of Na+, K+, Ca++, Mg++ and intracellular water in the treated cells and controls were correlated with the percentages of ultrastructural changes in the mitochondria of the cells. A moderate negative correlation (r = -0.66) was observed between K+ content of the cells and the condensation of mitochondria in selected experiments where mitochondrial swelling had not yet started. A moderate positive correlation (r = 0.44) was observed between mitochondrial condensation and Na+ content of the cells in the same experiments. K+ and Mg++ content of cells showed a moderate negative correlation (r = -0.58 and -0.65) with mitochondrial swelling in the material of all experiments and Ca++ content a moderate positive one (r = 0.58), but the Na+ content and intracellular water showed no correlation. The percentages of flocculent densities in mitochondria showed a moderate positive correlation (r = 0.43) with the Ca++ content of the cells and a moderate negative correlation (r = -0.61) with the magnesium content of the cells.", "contents": "Mitochondrial changes, ion and water shifts in the cellular injury of ehrlich ascites tumor cells. Cellular injury was produced in Ehlrich ascites tumor cells by an inhibitor of the function of the cell membrane [10(-3M) parachloromercuribenzenesulfonic acid (PCMBS)] or by inhibitors of respiration (10(-4M) Antimycin A), glycolysis (10(-4M), iodoacetic acid, IAA), oxidative phosphorylation (10(-3M) 2,4 dinitrophenol, DNP) or by combinations of these in a medium with or without glucose. The contents of Na+, K+, Ca++, Mg++ and intracellular water in the treated cells and controls were correlated with the percentages of ultrastructural changes in the mitochondria of the cells. A moderate negative correlation (r = -0.66) was observed between K+ content of the cells and the condensation of mitochondria in selected experiments where mitochondrial swelling had not yet started. A moderate positive correlation (r = 0.44) was observed between mitochondrial condensation and Na+ content of the cells in the same experiments. K+ and Mg++ content of cells showed a moderate negative correlation (r = -0.58 and -0.65) with mitochondrial swelling in the material of all experiments and Ca++ content a moderate positive one (r = 0.58), but the Na+ content and intracellular water showed no correlation. The percentages of flocculent densities in mitochondria showed a moderate positive correlation (r = 0.43) with the Ca++ content of the cells and a moderate negative correlation (r = -0.61) with the magnesium content of the cells."} {"id": "PMID:170905", "title": "Experimental investigations into the pathogenesis of endocarditis due to shock.", "content": "Generalized Shwartzman reaction (GSR) was induced in rabbits by two intravenous injections of endotoxin 24 hours apart. Consumption coagulopathy was found in all cases. Histological investigations showed an abacterial endocarditis (thrombotica or verruccosa simplex), comparable to the one seen in humans after shock, in 69% of the treated animals. Biopsies of mitral valve were investigated by electron microscopy. In the early stage of GSR the valvular alterations were characterized by an oedema of the entire valve, an increase in the number of microvesicles in the endothelial cytoplasm, and a marked enlargement of endothelial cell surface by numerous cytoplasmic projections. At a later stage autophagic vacuoles, often showing a destruction of their membranes, and degenerative changes in cytoplasmic organelles occurred in many cells of the valve. On the other hand there were cells in the endothelium, which presented a distinctly increased number of Golgi complexes and of cisternae of rough endoplasmic reticulum. In other regions ruptures of endothelial plasmalemma, as well as hemorrhages into the valvular stroma were observed. Thus predestined loci for thrombogenesis were formed. In conjunction with these structural changes three factors may be involved in the formation of endocarditis due to shock: 1. hypercoagulability in the course of consumption coagulopathy, leading to precipitation of fibrin and platelets in the circulating blood; 2. turbulences of the blood flow, which are produced by the closure of the heart valves, and favour thrombogenesis on valves: 3. direct changes of the endocardium during endotoxemia. Quantitative changes in the different compartments of intracytoplasmic organelles in many cells of the endothelium during the later stage of GSR are discussed.", "contents": "Experimental investigations into the pathogenesis of endocarditis due to shock. Generalized Shwartzman reaction (GSR) was induced in rabbits by two intravenous injections of endotoxin 24 hours apart. Consumption coagulopathy was found in all cases. Histological investigations showed an abacterial endocarditis (thrombotica or verruccosa simplex), comparable to the one seen in humans after shock, in 69% of the treated animals. Biopsies of mitral valve were investigated by electron microscopy. In the early stage of GSR the valvular alterations were characterized by an oedema of the entire valve, an increase in the number of microvesicles in the endothelial cytoplasm, and a marked enlargement of endothelial cell surface by numerous cytoplasmic projections. At a later stage autophagic vacuoles, often showing a destruction of their membranes, and degenerative changes in cytoplasmic organelles occurred in many cells of the valve. On the other hand there were cells in the endothelium, which presented a distinctly increased number of Golgi complexes and of cisternae of rough endoplasmic reticulum. In other regions ruptures of endothelial plasmalemma, as well as hemorrhages into the valvular stroma were observed. Thus predestined loci for thrombogenesis were formed. In conjunction with these structural changes three factors may be involved in the formation of endocarditis due to shock: 1. hypercoagulability in the course of consumption coagulopathy, leading to precipitation of fibrin and platelets in the circulating blood; 2. turbulences of the blood flow, which are produced by the closure of the heart valves, and favour thrombogenesis on valves: 3. direct changes of the endocardium during endotoxemia. Quantitative changes in the different compartments of intracytoplasmic organelles in many cells of the endothelium during the later stage of GSR are discussed."} {"id": "PMID:170906", "title": "Malignant lymphoma resembling Burkitt's tumour in rhesus monkeys: (light- and electron microscopic studies).", "content": "Spontaneous tumours of the haematopoetic system have been only rarely observed in nonhuman primates. We had the opportunity to carry out light and electron microscopic investigations of three lymphomas in immature rhesus monkeys from our colony. All animals had tumours of both retroperitoneum and lymph nodes. The relatively uniform lymphoblastic or lymphoreticular tumour cells as well as the massive occurence of the so-called \"starry sky macrophages\" were histologically characteristic. Histochemically, the marked pyroninophilia of these tumour cells was evident. The electron nicroscopy revealed the tumour cells as lymphoblasts of about 8 mu diameter with the following features: round or oval, occasionally deeply indented cell nuclei with relatively clear interchromatinic substance; mostly well developed nucleoli; sparsely, rough endoplasmatic reticulum; large numbers of free ribosomes and polyribosomes; a few large, bizzarre mitochondria, often situated at one pole; lipid vacuoles in some cells. These histological, cytological and electron microscopic characteristics correspond to those of the human Burkitt's Lymphoma. This tumour is classified as an undifferentiated malignant lymphoma. Tumours of this type are of particular interest on comparative and epidemiological reasons in light of the existence of morphologically similar experimental, virus induced lymphomas in monkeys.", "contents": "Malignant lymphoma resembling Burkitt's tumour in rhesus monkeys: (light- and electron microscopic studies). Spontaneous tumours of the haematopoetic system have been only rarely observed in nonhuman primates. We had the opportunity to carry out light and electron microscopic investigations of three lymphomas in immature rhesus monkeys from our colony. All animals had tumours of both retroperitoneum and lymph nodes. The relatively uniform lymphoblastic or lymphoreticular tumour cells as well as the massive occurence of the so-called \"starry sky macrophages\" were histologically characteristic. Histochemically, the marked pyroninophilia of these tumour cells was evident. The electron nicroscopy revealed the tumour cells as lymphoblasts of about 8 mu diameter with the following features: round or oval, occasionally deeply indented cell nuclei with relatively clear interchromatinic substance; mostly well developed nucleoli; sparsely, rough endoplasmatic reticulum; large numbers of free ribosomes and polyribosomes; a few large, bizzarre mitochondria, often situated at one pole; lipid vacuoles in some cells. These histological, cytological and electron microscopic characteristics correspond to those of the human Burkitt's Lymphoma. This tumour is classified as an undifferentiated malignant lymphoma. Tumours of this type are of particular interest on comparative and epidemiological reasons in light of the existence of morphologically similar experimental, virus induced lymphomas in monkeys."} {"id": "PMID:170907", "title": "Thermography and rheumatic diseases.", "content": "The common factor in most of the rheumatic diseases is an arthritis. Radiometry and thermography have been shown to indicate and measure heat resulting from localised inflammation. In rheumatoid arthritis, juvenile arthritis, osteoarthrosis, gout and ankylosing spondylitis abnormal heat distribution has been recorded over affected joints. Experimental evidence has shown that temperature change reflects the inflammatory state of the joint, and that this may be used to measure the effect of therapy by oral, systemic and local drug therapy, and also surgery, i.e. synovectomy.", "contents": "Thermography and rheumatic diseases. The common factor in most of the rheumatic diseases is an arthritis. Radiometry and thermography have been shown to indicate and measure heat resulting from localised inflammation. In rheumatoid arthritis, juvenile arthritis, osteoarthrosis, gout and ankylosing spondylitis abnormal heat distribution has been recorded over affected joints. Experimental evidence has shown that temperature change reflects the inflammatory state of the joint, and that this may be used to measure the effect of therapy by oral, systemic and local drug therapy, and also surgery, i.e. synovectomy."} {"id": "PMID:170908", "title": "Esterase-6 (Es-6) in laboratory mice: hormone-influenced expression and linkage relationship to oligosyndactylism (Os), esterase-1 (Es-1), and esterase-2 (Es-2) in chromosome 8.", "content": "Allelic differences at an esterase locus designated Es-6 exist between mouse strain C57 BL/6J and a laboratory stock of M.m. molossinus. Strain C57BL/6J has been assigned the allele Es-6a and M. m. molossinus the alternate allele Es-6b. Kidney expression of the electrophoretic esterase band controlled by the Es-6 locus is sex influenced, with increased activity apparently induced by testosterone. A four-point test cross established the gene order Os-Es-1-Es-6-Es-2 within a 10-cM segment on chromosome 8.", "contents": "Esterase-6 (Es-6) in laboratory mice: hormone-influenced expression and linkage relationship to oligosyndactylism (Os), esterase-1 (Es-1), and esterase-2 (Es-2) in chromosome 8. Allelic differences at an esterase locus designated Es-6 exist between mouse strain C57 BL/6J and a laboratory stock of M.m. molossinus. Strain C57BL/6J has been assigned the allele Es-6a and M. m. molossinus the alternate allele Es-6b. Kidney expression of the electrophoretic esterase band controlled by the Es-6 locus is sex influenced, with increased activity apparently induced by testosterone. A four-point test cross established the gene order Os-Es-1-Es-6-Es-2 within a 10-cM segment on chromosome 8."} {"id": "PMID:170909", "title": "Initial expression of the genes for fructose 1,6-diphosphatase, malic enzyme, and aspartate aminotransferase in Japanese quail and chicken--quail hybrid embryos.", "content": "The initial appearance of a number of enzymes involved in gluconeogenesis was investigated in the early embryogenesis of the Japanese quail (Coturnix coturnix japonica), the domestic chicken (Gallus gallus domesticus), and chicken-quail hybrids. Starch gel electrophoresis and enzyme-specific stains revealed genetic differences between muscle and liver fructose 1,6-diphosphatase (FDPase) as well as malic enzyme (ME) and mitochondrial aspartate aminotransferase (AAT) isozymes of the two species. ME and AAT were present in unfertilized unincubated eggs, indicating maternal storage of these enzymes. The initial expression of the paternally inherited genes in the hybrid occurred before oviposition in the case of ME, and between 12 and 18 hr incubation in the case of AAT. Initial expression of both parental sets of genes for FDPase occurred synchronously between 16 and 24 hr in the hybrid, corresponding to the time of initial appearance of this enzyme in the quail and chicken. Glucose 6-phosphate administration at 0 hr was found to cause no prevention or delay of initial enzyme activation. These results are interpreted in terms of early patterns of enzyme activation regulation and nutrition in the avian embryo.", "contents": "Initial expression of the genes for fructose 1,6-diphosphatase, malic enzyme, and aspartate aminotransferase in Japanese quail and chicken--quail hybrid embryos. The initial appearance of a number of enzymes involved in gluconeogenesis was investigated in the early embryogenesis of the Japanese quail (Coturnix coturnix japonica), the domestic chicken (Gallus gallus domesticus), and chicken-quail hybrids. Starch gel electrophoresis and enzyme-specific stains revealed genetic differences between muscle and liver fructose 1,6-diphosphatase (FDPase) as well as malic enzyme (ME) and mitochondrial aspartate aminotransferase (AAT) isozymes of the two species. ME and AAT were present in unfertilized unincubated eggs, indicating maternal storage of these enzymes. The initial expression of the paternally inherited genes in the hybrid occurred before oviposition in the case of ME, and between 12 and 18 hr incubation in the case of AAT. Initial expression of both parental sets of genes for FDPase occurred synchronously between 16 and 24 hr in the hybrid, corresponding to the time of initial appearance of this enzyme in the quail and chicken. Glucose 6-phosphate administration at 0 hr was found to cause no prevention or delay of initial enzyme activation. These results are interpreted in terms of early patterns of enzyme activation regulation and nutrition in the avian embryo."} {"id": "PMID:170910", "title": "Purification, properties and amino acid sequence of atypical cytochrome c from two protozoa, Euglena gracilis and Crithidia oncopelti.", "content": "A basic cytochrome was isolated from the phytomastigophorean protozoan Euglena gracilis and a similar protein from the zoomastigophorean protozoan Crithidia oncopelti. In both cases chromatography on CM-cellulose in first the reduced and then the oxidized form proved to be an efficient means of purification. The two cytochromes can be classed in the cytochrome c family but they have certain atypical features. The alpha peak of the absorption spectrum is shifted towards the red and is asymmetrical. The pyridine ferrohaemochrome has an alpha-peak maximum intermediate between that of c-type cytochromes and proteins containing protohaem IX. The test for free vinyl groups was positive. The amino acid sequences of the two cytochromes were determined. Attention is drawn in the text to those parts of the evidence that are less satisfactory. Both sequences are homologous with the family of cytochrome c, but are unusual in having only one cysteine residue so that the haem is attached through only one thioether bond. Detailed evidence for the amino acid dequences of the two proteins has been deposited as Supplementary Publication SUP 50042 (70 pages) at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Wetherby, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1975) 145, 5.", "contents": "Purification, properties and amino acid sequence of atypical cytochrome c from two protozoa, Euglena gracilis and Crithidia oncopelti. A basic cytochrome was isolated from the phytomastigophorean protozoan Euglena gracilis and a similar protein from the zoomastigophorean protozoan Crithidia oncopelti. In both cases chromatography on CM-cellulose in first the reduced and then the oxidized form proved to be an efficient means of purification. The two cytochromes can be classed in the cytochrome c family but they have certain atypical features. The alpha peak of the absorption spectrum is shifted towards the red and is asymmetrical. The pyridine ferrohaemochrome has an alpha-peak maximum intermediate between that of c-type cytochromes and proteins containing protohaem IX. The test for free vinyl groups was positive. The amino acid sequences of the two cytochromes were determined. Attention is drawn in the text to those parts of the evidence that are less satisfactory. Both sequences are homologous with the family of cytochrome c, but are unusual in having only one cysteine residue so that the haem is attached through only one thioether bond. Detailed evidence for the amino acid dequences of the two proteins has been deposited as Supplementary Publication SUP 50042 (70 pages) at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Wetherby, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1975) 145, 5."} {"id": "PMID:170911", "title": "A study of the oxidation of butan-1-ol and propan-2-ol by nicotinamide-adenine dinucleotide catalysed by yeast alcohol dehydrogenase.", "content": "1. The kinetics of oxidation of butan-1-ol and propan-2-ol by NAD+, catalysed by yeast alcohol dehydrogenase, were studied at 25 degrees C from pH 5.5 to 10, and at pH 7.05 from 14 degrees to 44 degrees C, 2. Under all conditions studied the results are consistent with a mechanism whereby some dissociation of coenzyme from the active enzyme-NAD+-alcohol ternary complexes occurs, and the mechanism is therefore not strictly compulsory order. 3. A primary 2H isotopic effect on the maximum rates of oxidation of [1-2H2]butan-1-ol and [2H7]propan-2-ol was found at 25 degrees C over the pH range 5.5-10. Further, in stopped-flow experiments at pH 7.05 and 25 degrees C, there was no transient formation of NADH in the oxidation of butan-1-ol and propan-2-ol. The principal rate-limiting step in the oxidation of dependence on pH of the maximum rates of oxidation of butan-1-ol and propan-2-ol is consisten with the possibility that histidine and cysteine residues may affect or control catalysis.", "contents": "A study of the oxidation of butan-1-ol and propan-2-ol by nicotinamide-adenine dinucleotide catalysed by yeast alcohol dehydrogenase. 1. The kinetics of oxidation of butan-1-ol and propan-2-ol by NAD+, catalysed by yeast alcohol dehydrogenase, were studied at 25 degrees C from pH 5.5 to 10, and at pH 7.05 from 14 degrees to 44 degrees C, 2. Under all conditions studied the results are consistent with a mechanism whereby some dissociation of coenzyme from the active enzyme-NAD+-alcohol ternary complexes occurs, and the mechanism is therefore not strictly compulsory order. 3. A primary 2H isotopic effect on the maximum rates of oxidation of [1-2H2]butan-1-ol and [2H7]propan-2-ol was found at 25 degrees C over the pH range 5.5-10. Further, in stopped-flow experiments at pH 7.05 and 25 degrees C, there was no transient formation of NADH in the oxidation of butan-1-ol and propan-2-ol. The principal rate-limiting step in the oxidation of dependence on pH of the maximum rates of oxidation of butan-1-ol and propan-2-ol is consisten with the possibility that histidine and cysteine residues may affect or control catalysis."} {"id": "PMID:170912", "title": "A kinetic method to establish the specificity of spin labelling of macromolecules.", "content": "A method has been devised for establishing the specificity of spin labelling of a macromolecule. Analysis of the rate of incorporation of spin label under different conditions permits the assignment of reacting groups to classes of differing reactivity. The method is illustrated for the enzyme glycogen phosphorylase b.", "contents": "A kinetic method to establish the specificity of spin labelling of macromolecules. A method has been devised for establishing the specificity of spin labelling of a macromolecule. Analysis of the rate of incorporation of spin label under different conditions permits the assignment of reacting groups to classes of differing reactivity. The method is illustrated for the enzyme glycogen phosphorylase b."} {"id": "PMID:170913", "title": "Effects of anions on a monomeric and a dimeric arginine kinase.", "content": "1. Some effects of anions on the rates of phosphoarginine synthesis by monomeric (lobster) and by dimeric (Holothuria forskali) arginine kinases are reported. 2. As with creatine kinase, acetate ions activate both enzymes: Cl- was also found to activate both although this was an inhibitor of creatine kinase. 3. NO3- inhibits the lobster enzyme. Inhibition is of the mixed type with respect to MgATP. Ki greater than Ki' and Ks greater than Ks' indicating that the presence of NO3- promotes the binding of substrate and vice versa. 4. NO3- alone has no effect on the difference spectrum of the lobster enzyme but in the presence of arginine, MgATP, MgADP, MgAMP or MgIDP the difference spectrum is greatly enhanced. A profound effect on the ionization state of tyrosine residues is inferred. 5. With the Holothuria enzyme low concentrations of NO3- activate in a manner that is competitive with arginine. Higher concentrations cause inhibition of the mixed type with respect to arginine in a similar manner to that found with MgATP for the lobster kinase. 6. Of a range of anions tested only NO3- and NO2- enhanced the inhibition of enzyme activity by MgADP, indicating the formation of a pseudo-transition-state dead-end complex, enzyme-arginine-NO3--MgADP. The effect was essentially independent of temperature with the Holothuria enzyme, but with the lobster enzyme was much less marked and temperature dependent. The difference may reflect the different stabilities of the monomer and dimer enzymes, although with neither arginine kinase is the stabilization of the dead-end complex as marked as is found with creatinine kinase.", "contents": "Effects of anions on a monomeric and a dimeric arginine kinase. 1. Some effects of anions on the rates of phosphoarginine synthesis by monomeric (lobster) and by dimeric (Holothuria forskali) arginine kinases are reported. 2. As with creatine kinase, acetate ions activate both enzymes: Cl- was also found to activate both although this was an inhibitor of creatine kinase. 3. NO3- inhibits the lobster enzyme. Inhibition is of the mixed type with respect to MgATP. Ki greater than Ki' and Ks greater than Ks' indicating that the presence of NO3- promotes the binding of substrate and vice versa. 4. NO3- alone has no effect on the difference spectrum of the lobster enzyme but in the presence of arginine, MgATP, MgADP, MgAMP or MgIDP the difference spectrum is greatly enhanced. A profound effect on the ionization state of tyrosine residues is inferred. 5. With the Holothuria enzyme low concentrations of NO3- activate in a manner that is competitive with arginine. Higher concentrations cause inhibition of the mixed type with respect to arginine in a similar manner to that found with MgATP for the lobster kinase. 6. Of a range of anions tested only NO3- and NO2- enhanced the inhibition of enzyme activity by MgADP, indicating the formation of a pseudo-transition-state dead-end complex, enzyme-arginine-NO3--MgADP. The effect was essentially independent of temperature with the Holothuria enzyme, but with the lobster enzyme was much less marked and temperature dependent. The difference may reflect the different stabilities of the monomer and dimer enzymes, although with neither arginine kinase is the stabilization of the dead-end complex as marked as is found with creatinine kinase."} {"id": "PMID:170914", "title": "Glutamine and asparagine as nitrogen donors for reductant-dependent glutamate synthesis in pea roots.", "content": "Glutamine, in the presence of alpha-oxoglutarate, stimulates nicotinamide nucleotide oxidation by crude extracts of pea roots and leads to a reductant-dependent formation of glutamate. Commercially available asparagine also stimulates nicotinamide nucleotide oxidation in the presence of alpha-oxoglutarate, but the reaction causing the stimulation can occur in the absence of a reductant, is inhibited by transaminase inhibitors, and is additive to the glutamine reaction. The asparagine used was found to be contaminated with aspartate. Repurified asparagine, chromatographically free of aspartate, did not stimulate the rate of nicotinamide nucleotide oxidation, and it is probable that the original stimulation was due to aspartate contamination. It is concluded that pea-root glutamine (amide)-alpha-oxoglutarate aminotransferase (glutamate synthase), in common with the enzyme in leaves, is specific for glutamine as the N donor and alpha-oxoglutarate as the N acceptor. The significance of the enzyme in conjunction with glutamine synthetase in the assimilation of nitrate by roots is discussed.", "contents": "Glutamine and asparagine as nitrogen donors for reductant-dependent glutamate synthesis in pea roots. Glutamine, in the presence of alpha-oxoglutarate, stimulates nicotinamide nucleotide oxidation by crude extracts of pea roots and leads to a reductant-dependent formation of glutamate. Commercially available asparagine also stimulates nicotinamide nucleotide oxidation in the presence of alpha-oxoglutarate, but the reaction causing the stimulation can occur in the absence of a reductant, is inhibited by transaminase inhibitors, and is additive to the glutamine reaction. The asparagine used was found to be contaminated with aspartate. Repurified asparagine, chromatographically free of aspartate, did not stimulate the rate of nicotinamide nucleotide oxidation, and it is probable that the original stimulation was due to aspartate contamination. It is concluded that pea-root glutamine (amide)-alpha-oxoglutarate aminotransferase (glutamate synthase), in common with the enzyme in leaves, is specific for glutamine as the N donor and alpha-oxoglutarate as the N acceptor. The significance of the enzyme in conjunction with glutamine synthetase in the assimilation of nitrate by roots is discussed."} {"id": "PMID:170915", "title": "The distribution and partial characterization of the serum apolipoproteins in the guinea pig.", "content": "1. Very-low-density (VLD), low-density (LD) and high-density (HD) lipoproteins were isolated by sequential ultracentrifugation from the serum of male guinea pigs fed on a diet containing 3--4% fat. The apoproteins of these lipoproteins (apo-VLD, apo-LD and apo-HD lipoproteins) were studied after delipidation with organic solvents or extraction with tetramethylurea. 2. The major apolipoprotein of LD lipoprotein isolated by gel filtration was found to closely resemble apolipoprotein B of human serum in its chemical and physical properties. Electrophoresis in sodium dodecyl sulphate-polyacrylamide gel showed that this apoprotein consisted of a number of polypeptides. 3. Tetramethylurea precipitated an apoprotein from guinea-pig serum lipoproteins that is probably the apolipoprotein B-like component. This apoprotein accounted for about 80% of the apo-LD lipoprotein, about 55% of the apo-VLD lipoprotein and about 50% of the apo-HD lipoprotein. 4. The distribution of apolipoproteins soluble in tetramethylurea was determined by densitometric scanning of stained polyacrylamide disc gels. 5. A glycine-rich component of high electrophoretic mobility (band I) and a triplet of soluble apolipoproteins (bands II-IV) were present in both VLD and LD lipoprotein classes. These components constituted a higher proportion of the tetramethylurea-soluble apoproteins of VLD lipoprotein (60--80%) than of LD lipoprotein (40--55%). 6. Small amounts (10--15%) of a component of intermediate mobility, which contained traces of half-cystine, were also present in both VLD and LD lipoproteins. 7. A group of soluble components of basic character (bands VI-X), present as minor components of VLD lipoprotein (10--20%), constituted a major proportion (30--45%) of the soluble apoproteins of LD lipoprotein. Two of these apoproteins were rich in lysine, and two of lower electrophoretic mobility were rich in arginine. 8. The pattern of tetramethylurea-soluble apoproteins in HD lipoprotein was distinguished by the presence of two polypeptides of low electrophoretic mobility as its predominant components. One of these components, band VI, resembled the A-I apolipoprotein of man in both its amino acid profile and in its electrophoretic mobility. The second major component, band VI-B, was rich in lysine and resembled the C-I apolipoprotein of man in amino acid composition. 9. The soluble components of bands I and IX were analogous in physicochemical properties to the R-X1 and R-X2 (high-arginine polypeptide) peptides of human serum lipoproteins respectively.", "contents": "The distribution and partial characterization of the serum apolipoproteins in the guinea pig. 1. Very-low-density (VLD), low-density (LD) and high-density (HD) lipoproteins were isolated by sequential ultracentrifugation from the serum of male guinea pigs fed on a diet containing 3--4% fat. The apoproteins of these lipoproteins (apo-VLD, apo-LD and apo-HD lipoproteins) were studied after delipidation with organic solvents or extraction with tetramethylurea. 2. The major apolipoprotein of LD lipoprotein isolated by gel filtration was found to closely resemble apolipoprotein B of human serum in its chemical and physical properties. Electrophoresis in sodium dodecyl sulphate-polyacrylamide gel showed that this apoprotein consisted of a number of polypeptides. 3. Tetramethylurea precipitated an apoprotein from guinea-pig serum lipoproteins that is probably the apolipoprotein B-like component. This apoprotein accounted for about 80% of the apo-LD lipoprotein, about 55% of the apo-VLD lipoprotein and about 50% of the apo-HD lipoprotein. 4. The distribution of apolipoproteins soluble in tetramethylurea was determined by densitometric scanning of stained polyacrylamide disc gels. 5. A glycine-rich component of high electrophoretic mobility (band I) and a triplet of soluble apolipoproteins (bands II-IV) were present in both VLD and LD lipoprotein classes. These components constituted a higher proportion of the tetramethylurea-soluble apoproteins of VLD lipoprotein (60--80%) than of LD lipoprotein (40--55%). 6. Small amounts (10--15%) of a component of intermediate mobility, which contained traces of half-cystine, were also present in both VLD and LD lipoproteins. 7. A group of soluble components of basic character (bands VI-X), present as minor components of VLD lipoprotein (10--20%), constituted a major proportion (30--45%) of the soluble apoproteins of LD lipoprotein. Two of these apoproteins were rich in lysine, and two of lower electrophoretic mobility were rich in arginine. 8. The pattern of tetramethylurea-soluble apoproteins in HD lipoprotein was distinguished by the presence of two polypeptides of low electrophoretic mobility as its predominant components. One of these components, band VI, resembled the A-I apolipoprotein of man in both its amino acid profile and in its electrophoretic mobility. The second major component, band VI-B, was rich in lysine and resembled the C-I apolipoprotein of man in amino acid composition. 9. The soluble components of bands I and IX were analogous in physicochemical properties to the R-X1 and R-X2 (high-arginine polypeptide) peptides of human serum lipoproteins respectively."} {"id": "PMID:170916", "title": "Kinetic studies on the hydroxylation of p-coumaric acid to caffeic acid by spinach-beet phenolase.", "content": "1. A spectrophotometric assay is described that enables the hydroxylation of p-coumaric acid to caffeic acid, catalysed by spinach-beet phenolase, to be followed continuously. 2. Initial-velocity and inhibitor studies indicate that the order of substrate addition is oxygen, p-coumaric acid and electron donor, with an irreversible step separating the binding of each substrate. 3. Caffeic acid is most likely to act as electron donor at the active site; other electron donors, such as ascorbic acid, NADH and dimethyltetrahydropteridine, function mainly to recycle cofactor amounts of caffeic acid. 4. A reaction scheme, consistent with these data, is proposed.", "contents": "Kinetic studies on the hydroxylation of p-coumaric acid to caffeic acid by spinach-beet phenolase. 1. A spectrophotometric assay is described that enables the hydroxylation of p-coumaric acid to caffeic acid, catalysed by spinach-beet phenolase, to be followed continuously. 2. Initial-velocity and inhibitor studies indicate that the order of substrate addition is oxygen, p-coumaric acid and electron donor, with an irreversible step separating the binding of each substrate. 3. Caffeic acid is most likely to act as electron donor at the active site; other electron donors, such as ascorbic acid, NADH and dimethyltetrahydropteridine, function mainly to recycle cofactor amounts of caffeic acid. 4. A reaction scheme, consistent with these data, is proposed."} {"id": "PMID:170917", "title": "Studies on sex-organ development. Isolation and characterization of an oestrogen receptor from chick M\u00fcllerian duct.", "content": "An oestradiol-binding macromolecule was observed in the left M\u00fcllerian duct of the 15-day female chick embryo. The embryonic receptor binds oestradiol with a high affinity and low capacity, having a Kd of 3.2 X 10(-9)M and a maximal number of sites of 5.45 fmol/10(6) cells in the left M\u00fcllerian duct. The receptor is protein in nature, as suggested by its susceptibility to proteolysis; in addition, it is organ- and steroid-specific. Judging by glycerol-gradient analysis, the hormone receptors in the cytosol are present in 8S and 4.5S forms, and the 8S form could be dissociated into a 4.5S form in the presence of 0.5M-KCl. A 4.5-6S receptor could be extracted from the nuclei. Under physiological salt conditions, the embryonic receptors bind to DNA-cellulose and can be eluted when the salt concentration is increased to 0.5M-KCl. Determination by isoelectric focusing indicates that the isoelectric point is 5.8 for the 8S and 6.9 for the 4.5S receptor.", "contents": "Studies on sex-organ development. Isolation and characterization of an oestrogen receptor from chick M\u00fcllerian duct. An oestradiol-binding macromolecule was observed in the left M\u00fcllerian duct of the 15-day female chick embryo. The embryonic receptor binds oestradiol with a high affinity and low capacity, having a Kd of 3.2 X 10(-9)M and a maximal number of sites of 5.45 fmol/10(6) cells in the left M\u00fcllerian duct. The receptor is protein in nature, as suggested by its susceptibility to proteolysis; in addition, it is organ- and steroid-specific. Judging by glycerol-gradient analysis, the hormone receptors in the cytosol are present in 8S and 4.5S forms, and the 8S form could be dissociated into a 4.5S form in the presence of 0.5M-KCl. A 4.5-6S receptor could be extracted from the nuclei. Under physiological salt conditions, the embryonic receptors bind to DNA-cellulose and can be eluted when the salt concentration is increased to 0.5M-KCl. Determination by isoelectric focusing indicates that the isoelectric point is 5.8 for the 8S and 6.9 for the 4.5S receptor."} {"id": "PMID:170918", "title": "Studies on sex-organ development. Ontogeny of cytoplasmic oestrogen receptor in chick M\u00fcllerian duct.", "content": "Oestradiol receptors were observed in the cytoplasm of the chick M\u00fcllerian duct at several embryonic stages. The sedimentation coefficients and the dissociation constants of the receptor protein remained unchanged throughout the various stages of development. Specific binding of cytoplasmic receptor to [3H]oestradiol assayed in vitro was shown to be saturable at concentration of 10nM or higher. The number of oeastradiol-binding sites on a per-cell basis increased linearly from day 8 to day 12 of incubation and then levelled off from day 12 to the fourth day after hatching. These results indicate that in the developing embryonic sex organ, the same receptor protein is present throughout prenatal development. The concentration of the oestradiol receptor increases and reaches a constant value, but the capacity for the receptor to interact with the hormone does not change.", "contents": "Studies on sex-organ development. Ontogeny of cytoplasmic oestrogen receptor in chick M\u00fcllerian duct. Oestradiol receptors were observed in the cytoplasm of the chick M\u00fcllerian duct at several embryonic stages. The sedimentation coefficients and the dissociation constants of the receptor protein remained unchanged throughout the various stages of development. Specific binding of cytoplasmic receptor to [3H]oestradiol assayed in vitro was shown to be saturable at concentration of 10nM or higher. The number of oeastradiol-binding sites on a per-cell basis increased linearly from day 8 to day 12 of incubation and then levelled off from day 12 to the fourth day after hatching. These results indicate that in the developing embryonic sex organ, the same receptor protein is present throughout prenatal development. The concentration of the oestradiol receptor increases and reaches a constant value, but the capacity for the receptor to interact with the hormone does not change."} {"id": "PMID:170919", "title": "Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat.", "content": "The effect glucocorticoids on the synthesis and degradation of phosphoenolpyruvate carboxykinase (GTP)(EC4.1.1.32) in rat liver and kidney in vivo was studied immunochemically. The glucocorticoid analogue triamcinolone (9alpha-fluoro-11beta, 21-dihydroxy-16alpha,17alpha-isopropylidenedioxypregna-1,4-diene-3,20-dione) increased the synthesis rate of the kidney enzyme in starved animals. Both triamcinolone and cortisol decreased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP) in fed and starved rats, but were without effect on the degradation rate of the enzyme. This effect of triamcinolone in liver was reversed by injection of dibutyryl cyclic AMP. However, in diabetic animals glucocorticoids increased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP). Triamcinolone administration to starved rats in vivo is shown to cause an increase in the portal blood concentrations of insulin and glucose. Since the physiological de-inducer of liver phosphoenolpyruvate carboxykinase (GTP) is insulin, this is the probable cause of the decrease in the synthesis rate of the hepatic enzyme noted when glucocorticoids are administered to non-diabetic animals.", "contents": "Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat. The effect glucocorticoids on the synthesis and degradation of phosphoenolpyruvate carboxykinase (GTP)(EC4.1.1.32) in rat liver and kidney in vivo was studied immunochemically. The glucocorticoid analogue triamcinolone (9alpha-fluoro-11beta, 21-dihydroxy-16alpha,17alpha-isopropylidenedioxypregna-1,4-diene-3,20-dione) increased the synthesis rate of the kidney enzyme in starved animals. Both triamcinolone and cortisol decreased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP) in fed and starved rats, but were without effect on the degradation rate of the enzyme. This effect of triamcinolone in liver was reversed by injection of dibutyryl cyclic AMP. However, in diabetic animals glucocorticoids increased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP). Triamcinolone administration to starved rats in vivo is shown to cause an increase in the portal blood concentrations of insulin and glucose. Since the physiological de-inducer of liver phosphoenolpyruvate carboxykinase (GTP) is insulin, this is the probable cause of the decrease in the synthesis rate of the hepatic enzyme noted when glucocorticoids are administered to non-diabetic animals."} {"id": "PMID:170920", "title": "Progesterone synthesis of pig corpus luteum tissue during superfusion.", "content": "A modified superfusion technique is described with which it was demonstrated that the action of gonadotrophin on progesterone secretion by pig corpus luteum tissue is twofold, in that it first stimulates the rapid release of progesterone (either performed or partially synthesized), which is followed by prolonged synthesis of the steroid de novo from acetate.", "contents": "Progesterone synthesis of pig corpus luteum tissue during superfusion. A modified superfusion technique is described with which it was demonstrated that the action of gonadotrophin on progesterone secretion by pig corpus luteum tissue is twofold, in that it first stimulates the rapid release of progesterone (either performed or partially synthesized), which is followed by prolonged synthesis of the steroid de novo from acetate."} {"id": "PMID:170943", "title": "[The mechanism of action of bencyclane on smooth musculature].", "content": "Bencyclane (N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine-hydrogenfumarate, Fludilat), inhibits phosphodiesterase(PDE)-activity in vitro similarly to several other smooth muscle relaxants. Compared with papaverine this inhibitory effect of bencyclane on PDE is weak despite of its strong relaxant effect on smooth muscle, which is about equal to that of papaverine. 14C-Bencyclane is accumulated 8-fold in the smooth muscle tissue of bovine coronary arteries, indicating that relaxation is caused by 8-fold higher concentrations in the tissue than in the organ bath. A comparison of (corrected) ED50-values for relaxation with Ki-values for PDE-inhibition obtained with several PDE-inhibitors, including bencyclane, yields a significant correlation between both parameters. Since in subsequent studies in isolated tracheal muscle strips bencyclane at maximum relaxing concentrations did not increase cAMP, which was in contrast to the actions of papaverine or aminophylline, it is likely that bencyclane-induced smooth muscle relaxation is unrelated to inhibition of PDE or cAMP. In the same dose range in which bencyclane relaxes smooth muscles it exerts a non-specific antiadrenergic inhibitory effect, possibly due to its local anesthetic action at the cell membrane. It is also possible that the myocardial inhibitory effect of bencyclane is caused by a direct Ca++-antagonistic mechanism (Fleckenstein et al. 1971).", "contents": "[The mechanism of action of bencyclane on smooth musculature]. Bencyclane (N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine-hydrogenfumarate, Fludilat), inhibits phosphodiesterase(PDE)-activity in vitro similarly to several other smooth muscle relaxants. Compared with papaverine this inhibitory effect of bencyclane on PDE is weak despite of its strong relaxant effect on smooth muscle, which is about equal to that of papaverine. 14C-Bencyclane is accumulated 8-fold in the smooth muscle tissue of bovine coronary arteries, indicating that relaxation is caused by 8-fold higher concentrations in the tissue than in the organ bath. A comparison of (corrected) ED50-values for relaxation with Ki-values for PDE-inhibition obtained with several PDE-inhibitors, including bencyclane, yields a significant correlation between both parameters. Since in subsequent studies in isolated tracheal muscle strips bencyclane at maximum relaxing concentrations did not increase cAMP, which was in contrast to the actions of papaverine or aminophylline, it is likely that bencyclane-induced smooth muscle relaxation is unrelated to inhibition of PDE or cAMP. In the same dose range in which bencyclane relaxes smooth muscles it exerts a non-specific antiadrenergic inhibitory effect, possibly due to its local anesthetic action at the cell membrane. It is also possible that the myocardial inhibitory effect of bencyclane is caused by a direct Ca++-antagonistic mechanism (Fleckenstein et al. 1971)."} {"id": "PMID:170944", "title": "Inhibition of platelet cyclic 3',5'-adenosine-monophosphate phosphodiesterases by pentifylline.", "content": "Pentifylline (1-hexyl-3,7-dimethylxanthine equals SK 7, the main active principle in Cosaldon) inhibits the soluble and the particulate cyclic AMP phosphodiesterases (PDE I and PDE II) from bovine platelets. I50 PDE I equals 2.0 x 10(-3)M; I50 PDE II equals 8.1 x 10(-4)M. The type of inhibition of both PDE's was non-competitive.", "contents": "Inhibition of platelet cyclic 3',5'-adenosine-monophosphate phosphodiesterases by pentifylline. Pentifylline (1-hexyl-3,7-dimethylxanthine equals SK 7, the main active principle in Cosaldon) inhibits the soluble and the particulate cyclic AMP phosphodiesterases (PDE I and PDE II) from bovine platelets. I50 PDE I equals 2.0 x 10(-3)M; I50 PDE II equals 8.1 x 10(-4)M. The type of inhibition of both PDE's was non-competitive."} {"id": "PMID:170945", "title": "[The mode of action of bisacodyl on the smooth muscle of the small and the large intestine of the guinea pig].", "content": "4,4'-Diacetoxy-diphenyl-(pyridyl-2)-methan (Bisacodyl, Dulcolax, 12--240 mug/ml) was shown to initiate dose-dependently contracile responses in the guinea pig isolated terminal ileum and taenia coli (a preparation of pure longitudinal muscle fibers). In contrast to muscle contractions induced by 1 mug/ml acetylcholine (ACh) and 1 mug/ml histamine, respectively bis-acodyl-induced contractile responses were antagonized neither by the anticholinergic agent atropine (6 mug/ml) nor by the antihistaminic compound pheniramine (6 mug/ml). On the other hand, bisacodyl inhibited contractile responses induced by ACh or histamine in a dose-dependent manner. The possibility that bisacodyl-induced contractions were due to a fall in cyclic 3,5-AMP level was excluded by estimation of endogenous cyclo-AMP. Since exogenous cyclic 3,5-AMP (which should possess calcium-antagonistic properties in smooth muscle) as well as verapamil (a calcium inhibitor) inhibited bisacodyl-induced contractions, a site of action on the calcium-dependent contractile system of the smooth muscle cell was discussed. Furthermore, bisacodyl should diminish the sensibility of the contractile system to other contractile compounds (ACh, histamine).", "contents": "[The mode of action of bisacodyl on the smooth muscle of the small and the large intestine of the guinea pig]. 4,4'-Diacetoxy-diphenyl-(pyridyl-2)-methan (Bisacodyl, Dulcolax, 12--240 mug/ml) was shown to initiate dose-dependently contracile responses in the guinea pig isolated terminal ileum and taenia coli (a preparation of pure longitudinal muscle fibers). In contrast to muscle contractions induced by 1 mug/ml acetylcholine (ACh) and 1 mug/ml histamine, respectively bis-acodyl-induced contractile responses were antagonized neither by the anticholinergic agent atropine (6 mug/ml) nor by the antihistaminic compound pheniramine (6 mug/ml). On the other hand, bisacodyl inhibited contractile responses induced by ACh or histamine in a dose-dependent manner. The possibility that bisacodyl-induced contractions were due to a fall in cyclic 3,5-AMP level was excluded by estimation of endogenous cyclo-AMP. Since exogenous cyclic 3,5-AMP (which should possess calcium-antagonistic properties in smooth muscle) as well as verapamil (a calcium inhibitor) inhibited bisacodyl-induced contractions, a site of action on the calcium-dependent contractile system of the smooth muscle cell was discussed. Furthermore, bisacodyl should diminish the sensibility of the contractile system to other contractile compounds (ACh, histamine)."} {"id": "PMID:170946", "title": "Enhancement of phagocytosis by Compound 48/80 and its influence upon Ca++-dependent ATP-ase.", "content": "A new activity of p-methoxy-phenylethyl-methyl-amine condensed by formaldehyde (Cpd 48/80) has been established: enhancement of phagocytosis. This property seems to be correlated to its ability to activate lysosomes. Enhancement of phagocytosis is discussed in relation to the virus penetration process. Furthermore it was found that Cpd 48/80 and to a smaller degree the dimer inhibit the Ca++-dependent ATP-ase (E. C. 3.6.1.3.) from human red blood cells. The enzyme from bovine myosin is not inhibited by the dimer, but somewhat more by poly-THIQ (7-methoxy-tetrahydroisoquinoline condensed by formaldehyde) than by Cpd 48/80. These properties are discussed in relation to a general hypothesis of virus-induced giant cell formation. Finally it has been shown that the drug does not influence the PHA-stimulation (phytohemagglutinin) of lymphocytes, indicating selectivity of its activity.", "contents": "Enhancement of phagocytosis by Compound 48/80 and its influence upon Ca++-dependent ATP-ase. A new activity of p-methoxy-phenylethyl-methyl-amine condensed by formaldehyde (Cpd 48/80) has been established: enhancement of phagocytosis. This property seems to be correlated to its ability to activate lysosomes. Enhancement of phagocytosis is discussed in relation to the virus penetration process. Furthermore it was found that Cpd 48/80 and to a smaller degree the dimer inhibit the Ca++-dependent ATP-ase (E. C. 3.6.1.3.) from human red blood cells. The enzyme from bovine myosin is not inhibited by the dimer, but somewhat more by poly-THIQ (7-methoxy-tetrahydroisoquinoline condensed by formaldehyde) than by Cpd 48/80. These properties are discussed in relation to a general hypothesis of virus-induced giant cell formation. Finally it has been shown that the drug does not influence the PHA-stimulation (phytohemagglutinin) of lymphocytes, indicating selectivity of its activity."} {"id": "PMID:170947", "title": "Actions of various methylxanthines and papaverine on the synthesis of corticosterone in vitro.", "content": "Actions of various methylxanthines (theophylline, theobromine, caffeine) and papaverine, i.e. drugs which are known to inhibit phosphodiesterase (PDE), were studied on the basal and stimulated synthesis of corticosterone in vitro by using rat adrenal slices. When slices were incubated with methylxanthines, the synthesis of corticosterone was slightly increased. The order of potency, expressed as the efficacy (intrinsic activity) was: theophylline greater than caffeine greather than theobromine. Papaverine did not stimulate the synthesis. The synthesis stimulated by ACTH or the dibutyryl derivative of c-AMP (DBA) was reduced by all of the inhibitors of phosphodiesterase. The molar concentration of the inhibitors which reduced the stimulated steroidogenesis by 50% was lowest for papaverine, higher for theobromine and theophylline and highest for caffeine. Papaverine was active in concentrations of about 10(-5)M, while the methylxanthines were effective in concentrations of 10(-3)--10(-2)M. When the PDE-inhibitors were added to the incubate simultaneously with the stimulant (ACTH or DBA), there was a delay of 60 min before the synthesis was completely blocked. When the stimulant was added 30 min before the administration of an inhibitor, the inhibitory action was no more evident. The inhibitory action of theophylline, but not that of papaverine, was reversed by washing adrenal slices free from the inhibitor, before adding the stimulant. The type of inhibition for papaverine as well as for methylxanthines in antagonizing both the ACTH- and DBA-stimulated synthesis of corticosterone was not competitive but of a mixed type.", "contents": "Actions of various methylxanthines and papaverine on the synthesis of corticosterone in vitro. Actions of various methylxanthines (theophylline, theobromine, caffeine) and papaverine, i.e. drugs which are known to inhibit phosphodiesterase (PDE), were studied on the basal and stimulated synthesis of corticosterone in vitro by using rat adrenal slices. When slices were incubated with methylxanthines, the synthesis of corticosterone was slightly increased. The order of potency, expressed as the efficacy (intrinsic activity) was: theophylline greater than caffeine greather than theobromine. Papaverine did not stimulate the synthesis. The synthesis stimulated by ACTH or the dibutyryl derivative of c-AMP (DBA) was reduced by all of the inhibitors of phosphodiesterase. The molar concentration of the inhibitors which reduced the stimulated steroidogenesis by 50% was lowest for papaverine, higher for theobromine and theophylline and highest for caffeine. Papaverine was active in concentrations of about 10(-5)M, while the methylxanthines were effective in concentrations of 10(-3)--10(-2)M. When the PDE-inhibitors were added to the incubate simultaneously with the stimulant (ACTH or DBA), there was a delay of 60 min before the synthesis was completely blocked. When the stimulant was added 30 min before the administration of an inhibitor, the inhibitory action was no more evident. The inhibitory action of theophylline, but not that of papaverine, was reversed by washing adrenal slices free from the inhibitor, before adding the stimulant. The type of inhibition for papaverine as well as for methylxanthines in antagonizing both the ACTH- and DBA-stimulated synthesis of corticosterone was not competitive but of a mixed type."} {"id": "PMID:170948", "title": "Response of plasma lipid fractions to the administration of exogenous phospholipids.", "content": "Plasma lipidic fractions (total lipids, free and total cholesterol, triglycerides, total phospholipids and low density lipoproteins) of 16 hyperlipemic subjects have been followed up over a 4-week period. Intravenous injection of exogenous phospholipids prepared from pig heart resulted in a significant decrease of all the examined lipidic fractions. The possible mechanims of exogenous phospholipids action is discussed.", "contents": "Response of plasma lipid fractions to the administration of exogenous phospholipids. Plasma lipidic fractions (total lipids, free and total cholesterol, triglycerides, total phospholipids and low density lipoproteins) of 16 hyperlipemic subjects have been followed up over a 4-week period. Intravenous injection of exogenous phospholipids prepared from pig heart resulted in a significant decrease of all the examined lipidic fractions. The possible mechanims of exogenous phospholipids action is discussed."} {"id": "PMID:170949", "title": "[Controlled application of cynarin in the treatment of hyperlipemic syndrome. Observations in 60 cases].", "content": "In a controlled trial 2 groups of 30 patients presenting various dislipidemic pictures were treated for 50 days with either 3,5-dihydroxy-1,4-bis-(3,4-dihydroxy-cinnamoyloxy)-cyclohexan-carbonic acid-(1) (cynarin, Listrocol) or placebo. Cynarin provied to be able to induce a significant reduction of the hypercholesteremia, the level of pre-beta-lipoproteins, the beta/alpha-lipoprotein ratio and patients' body weight. The administration of cynaria is, therefore, deemed useful in the prophylaxis and therapy of dislipidemic pictures of the arteriosclerotic disease.", "contents": "[Controlled application of cynarin in the treatment of hyperlipemic syndrome. Observations in 60 cases]. In a controlled trial 2 groups of 30 patients presenting various dislipidemic pictures were treated for 50 days with either 3,5-dihydroxy-1,4-bis-(3,4-dihydroxy-cinnamoyloxy)-cyclohexan-carbonic acid-(1) (cynarin, Listrocol) or placebo. Cynarin provied to be able to induce a significant reduction of the hypercholesteremia, the level of pre-beta-lipoproteins, the beta/alpha-lipoprotein ratio and patients' body weight. The administration of cynaria is, therefore, deemed useful in the prophylaxis and therapy of dislipidemic pictures of the arteriosclerotic disease."} {"id": "PMID:170952", "title": "The relation of immune response to pathogenesis, vaccination and epidemiology in virus induced leukaemia.", "content": "The antigenic systems of oncornaviruses and particularly feline leukaemia virus (FeLV) are reviewed briefly. The use of immunological methods in studying the epidemiology of the disease is described. The incidence of FeLV infection as judged by a serological survey is at least 100 times greater than that of leukaemia in the cat population. Horizontal transmission, due to virus replication in respiratory and alimentary epithelial cells, is common. A method of producing high titres of antibody against membrane antigens of virus infected cells is described; the use of such vaccination is discussed in relation to several epidemiological facets of feline leukaemia virus infection. Leukaemia viruses are well known to cause immunodepression to heterologous antigens. The hypothesis is advanced that depression of the humoral antibody response to leukaemia virus antigens and cell membrane antigens may be an early event allowing establishment and replication of virus in haemic and the lymphatic tissues. Subsequent depression of cell mediated immunity through direct action of thymic cells is known to take place in the cat system. This may allow further spread of the virus with replication in epithelial cells which are not susceptible to cytotoxic action. Thus the primary events leading to leukaemogenesis may be an interplay between immunostimulation and immunodepression.", "contents": "The relation of immune response to pathogenesis, vaccination and epidemiology in virus induced leukaemia. The antigenic systems of oncornaviruses and particularly feline leukaemia virus (FeLV) are reviewed briefly. The use of immunological methods in studying the epidemiology of the disease is described. The incidence of FeLV infection as judged by a serological survey is at least 100 times greater than that of leukaemia in the cat population. Horizontal transmission, due to virus replication in respiratory and alimentary epithelial cells, is common. A method of producing high titres of antibody against membrane antigens of virus infected cells is described; the use of such vaccination is discussed in relation to several epidemiological facets of feline leukaemia virus infection. Leukaemia viruses are well known to cause immunodepression to heterologous antigens. The hypothesis is advanced that depression of the humoral antibody response to leukaemia virus antigens and cell membrane antigens may be an early event allowing establishment and replication of virus in haemic and the lymphatic tissues. Subsequent depression of cell mediated immunity through direct action of thymic cells is known to take place in the cat system. This may allow further spread of the virus with replication in epithelial cells which are not susceptible to cytotoxic action. Thus the primary events leading to leukaemogenesis may be an interplay between immunostimulation and immunodepression."} {"id": "PMID:170953", "title": "Marek's disease--the disease and its prevention by vaccination.", "content": "Marek's disease (MD) is a common lymphoproliferative disease of the domestic chicken caused by a cell associated herpesvirus. Vaccines used for the prophylaxis of MD have been derived from non-pathogenic field Marek's disease virus (MDV), pathogenic MDV and the herpesvirus of turkeys (HVT). Vaccines derived from MDV have been developed by attenuation of virus strains which produce the acute form of MD and virus strains which produce the classical form. They have also been developed by suitable modification, where necessary, of non-pathogenic MDV. All MDV derived vaccines have to be used in the cell associated form. The turkey herpesvirus vaccine can be used in either the cell associated or cell free lyophilized form. All these types of vaccine appear to be safe and to provide significant levels of protection under field conditions.", "contents": "Marek's disease--the disease and its prevention by vaccination. Marek's disease (MD) is a common lymphoproliferative disease of the domestic chicken caused by a cell associated herpesvirus. Vaccines used for the prophylaxis of MD have been derived from non-pathogenic field Marek's disease virus (MDV), pathogenic MDV and the herpesvirus of turkeys (HVT). Vaccines derived from MDV have been developed by attenuation of virus strains which produce the acute form of MD and virus strains which produce the classical form. They have also been developed by suitable modification, where necessary, of non-pathogenic MDV. All MDV derived vaccines have to be used in the cell associated form. The turkey herpesvirus vaccine can be used in either the cell associated or cell free lyophilized form. All these types of vaccine appear to be safe and to provide significant levels of protection under field conditions."} {"id": "PMID:170954", "title": "On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions.", "content": "When epidermis from the uninvolved skin of psoriatic patients was incubated for 5 min in Hank's medium containing adrenaline and theophylline, the cyclic AMP level consistently increased 20-30 times over the level observed when adrenaline was not added to the medium. On the other hand, when epidermis from the involved skin of psoriatic patients was incubated under the same experimental conditions, the cyclic AMP level increased only 2-5 times. Even when theophylline, and inhibitor of specific cyclic AMP-phosphodiesterase, was omitted from the medium, a clearly demonstrable difference in sensitivity to adrenaline was evident in normal appearing and lesional psoriatic epidermis. These results indicate a faulty adenyl cyclase system in the involved epidermis of psoriatic lesions rather than a defective degradation process by the specific phosphodiesterase. Since the Km for adrenaline activation of adenyl cyclase was approximately the same in both the uninvolved and the involved epidermis and since the cyclic AMP increase by adrenaline was abolished by the addition of propranolol, the basic nature of the beta-receptor (specifically the binding affinity to adrenaline) in the involved epidermis does not appear to be defective. On the other hand, the finding that the Vmax for adrenaline activation is 10-20 times higher in the uninvolved than in the involved epidermis suggests that the poor response in the involved epidermis may be due to fewer available binding sites for adrenaline in the psoriatic lesion.", "contents": "On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions. When epidermis from the uninvolved skin of psoriatic patients was incubated for 5 min in Hank's medium containing adrenaline and theophylline, the cyclic AMP level consistently increased 20-30 times over the level observed when adrenaline was not added to the medium. On the other hand, when epidermis from the involved skin of psoriatic patients was incubated under the same experimental conditions, the cyclic AMP level increased only 2-5 times. Even when theophylline, and inhibitor of specific cyclic AMP-phosphodiesterase, was omitted from the medium, a clearly demonstrable difference in sensitivity to adrenaline was evident in normal appearing and lesional psoriatic epidermis. These results indicate a faulty adenyl cyclase system in the involved epidermis of psoriatic lesions rather than a defective degradation process by the specific phosphodiesterase. Since the Km for adrenaline activation of adenyl cyclase was approximately the same in both the uninvolved and the involved epidermis and since the cyclic AMP increase by adrenaline was abolished by the addition of propranolol, the basic nature of the beta-receptor (specifically the binding affinity to adrenaline) in the involved epidermis does not appear to be defective. On the other hand, the finding that the Vmax for adrenaline activation is 10-20 times higher in the uninvolved than in the involved epidermis suggests that the poor response in the involved epidermis may be due to fewer available binding sites for adrenaline in the psoriatic lesion."} {"id": "PMID:170955", "title": "Chloroperoxidase: P-450 type absorption in the absence of sulfhydryl groups.", "content": "The oxidation state of the two half-cystine residues in the native ferric form of chloroperoxidase and in the reduced ferrous chloroperoxidase has been examined in order to evaluate the role of sulfhydryl groups as determinants of P-450 type spectra. M\u00f6ssbauer and optical spectroscopy studies indicate that the ferrous forms of P-450cam and chloroperoxidase have very similar or identical heme environments. Model studies have suggested that sulfhydryl groups may function as axial ligands for developing P-450 character. However, chemical studies involving both sulfhydryl reagents and amperometric titrations show that neither the ferric nor the chemically produced ferrous forms of chloroperoxidase contain a sulfhydryl group. These results rule out the hypothesis that sulfhydryl groups are unique components for P-450 absorption characteristics. The optical and electron paramagnetic resonance (EPR) spectra of the nitric oxide complex of chloroperoxidase have been obtained and compared to those of myoglobin, hemoglobin, and cytochrome c and horseradish peroxidase. The EPR spectrum of the NO-ferrous chloroperoxidase complex, which is similar to that of cytochrome P-450cam, does not show the extra nitrogen hyperfine structure which appears to be characteristic of those hemoproteins which have a nitrogen atom as an axial heme ligand.", "contents": "Chloroperoxidase: P-450 type absorption in the absence of sulfhydryl groups. The oxidation state of the two half-cystine residues in the native ferric form of chloroperoxidase and in the reduced ferrous chloroperoxidase has been examined in order to evaluate the role of sulfhydryl groups as determinants of P-450 type spectra. M\u00f6ssbauer and optical spectroscopy studies indicate that the ferrous forms of P-450cam and chloroperoxidase have very similar or identical heme environments. Model studies have suggested that sulfhydryl groups may function as axial ligands for developing P-450 character. However, chemical studies involving both sulfhydryl reagents and amperometric titrations show that neither the ferric nor the chemically produced ferrous forms of chloroperoxidase contain a sulfhydryl group. These results rule out the hypothesis that sulfhydryl groups are unique components for P-450 absorption characteristics. The optical and electron paramagnetic resonance (EPR) spectra of the nitric oxide complex of chloroperoxidase have been obtained and compared to those of myoglobin, hemoglobin, and cytochrome c and horseradish peroxidase. The EPR spectrum of the NO-ferrous chloroperoxidase complex, which is similar to that of cytochrome P-450cam, does not show the extra nitrogen hyperfine structure which appears to be characteristic of those hemoproteins which have a nitrogen atom as an axial heme ligand."} {"id": "PMID:170956", "title": "Infrared linear dichroism investigations of deoxyribonucleic acid complexes with poly(L-arginine) and poly(L-lysine).", "content": "Complexes between DNAs from various sources and poly(L-lysine) and poly(L-arginine) were studied by means of infrared linear dichroism. The measurements of dichroic ratios allowed us to determine the orientation of the phosphate group of DNA in the complexes with basic polypeptides. At high relative humidities (higher than 90%, B form), the bisector of the less than OPO in the complexes forms an angle with respect to the helical axis which has a value lower by about 4 degrees than in the corresponding DNA sample. This change of orientation of the phosphate group of DNA indicates a modification of the B form upon binding of polylysine or polyarginine. The structural transitions B leads to A and B leads to C measured as a function of relative humidities were not affected by formation of complexes with both basic polypeptides. Similar results were obtained for complexes prepared by direct mixing or by salt gradient dialysis. The presence of A and C forms was observed in complexes of DNA with poly(L-lysine) and poly(L-arginine) at lower relative humidity. Thus, the conformational flexibility of DNA in complexes with polylysine and polyarginine is not changed despite a substantial increase in the Tm (melting temperature). These results are considered as a model for the understanding of interactions between DNA and histones particularly of the binding of the N-terminal fragment, lysine or arginine rich.", "contents": "Infrared linear dichroism investigations of deoxyribonucleic acid complexes with poly(L-arginine) and poly(L-lysine). Complexes between DNAs from various sources and poly(L-lysine) and poly(L-arginine) were studied by means of infrared linear dichroism. The measurements of dichroic ratios allowed us to determine the orientation of the phosphate group of DNA in the complexes with basic polypeptides. At high relative humidities (higher than 90%, B form), the bisector of the less than OPO in the complexes forms an angle with respect to the helical axis which has a value lower by about 4 degrees than in the corresponding DNA sample. This change of orientation of the phosphate group of DNA indicates a modification of the B form upon binding of polylysine or polyarginine. The structural transitions B leads to A and B leads to C measured as a function of relative humidities were not affected by formation of complexes with both basic polypeptides. Similar results were obtained for complexes prepared by direct mixing or by salt gradient dialysis. The presence of A and C forms was observed in complexes of DNA with poly(L-lysine) and poly(L-arginine) at lower relative humidity. Thus, the conformational flexibility of DNA in complexes with polylysine and polyarginine is not changed despite a substantial increase in the Tm (melting temperature). These results are considered as a model for the understanding of interactions between DNA and histones particularly of the binding of the N-terminal fragment, lysine or arginine rich."} {"id": "PMID:170957", "title": "Purification of SV-40 messenger RNA by hybridization to SV-40 DNA covalently bound to Sepharose.", "content": "SV-40 DNA sheared form was coupled in a stable covalent bond to cyanogen bromide activated Sepharose. Under the conditions used at least 80% of the DNA was bound to Sepharose. The T 1/2 of hybridization of 0.5 mug/ml of SV-40 cRNA to SV-40 DNA-Sepharose was 1 hr. This rate of hybridization is sufficiently rapid to purify SV-40 sequences from solutions containing as little as 0.05-0.1 mug/ml. Nonspecific hybridization of RNA is in the range of 0.1-0.2% of the total input RNA. The DNA-Sepharose is fairly stable and can be reused several times to purify RNA. The SV-40 DNA-Sepharose was used to select large quantities of virus specific RNA from SV-40 infected BS-C-1 cells. The virus specific RNA when added to cell-free extracts from wheat germ was shown to direct the synthesis of the major viral structural protein VP-1.", "contents": "Purification of SV-40 messenger RNA by hybridization to SV-40 DNA covalently bound to Sepharose. SV-40 DNA sheared form was coupled in a stable covalent bond to cyanogen bromide activated Sepharose. Under the conditions used at least 80% of the DNA was bound to Sepharose. The T 1/2 of hybridization of 0.5 mug/ml of SV-40 cRNA to SV-40 DNA-Sepharose was 1 hr. This rate of hybridization is sufficiently rapid to purify SV-40 sequences from solutions containing as little as 0.05-0.1 mug/ml. Nonspecific hybridization of RNA is in the range of 0.1-0.2% of the total input RNA. The DNA-Sepharose is fairly stable and can be reused several times to purify RNA. The SV-40 DNA-Sepharose was used to select large quantities of virus specific RNA from SV-40 infected BS-C-1 cells. The virus specific RNA when added to cell-free extracts from wheat germ was shown to direct the synthesis of the major viral structural protein VP-1."} {"id": "PMID:170958", "title": "8-Substituted derivatives of adenosine 3',5'-cyclic phosphate require an unsubstituted 2'-hydroxyl group in the ribo configuration for biological activity.", "content": "Derivatives of adenosine 3',5'-cyclic phosphate (cAMP) with modifications in both the 2' and the 8 positions were synthesized and their enzymic activities as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterases were determined. Three types of derivatives were investigated: 8-substituted derivatives of O2'-Bt-cAMP, 8-substituted derivatives of 9-beta-D-arabinofuranosyladenine 3',5'-cyclic phosphate (ara-cAMP), and 8-substituted derivatives of 8,2'-anhydro-9-beta-D-arabinofuranosyladenine 3,'5'-cyclic phosphate (8,2'-anhydro-cAMP). The 8-substituted O2'-Bt-cAMP derivatives were synthesized by acylation of the preformed 8-substituted cAMP (8-HS-cAMP, 8-MeS-cAMP, and 8-PhCH2S-cAMP). 8-Br-O2'-tosyl-cAMP was sued as an intermediate for the preparation of 8,2'-anhydro-cAMP derivatives (8-HO-, 8-SH-, 8-H2N-, and 8-H3 CHN derivatives of 8,2'-anhydro-cAMP). 8-Substituted ara-cAMP derivatives were obtained by ring opening of 8-HO-8,2'-anhydro-cAMP with H+/H2O, NH3/MeOH, or MeONa/MeOH (to yield the 8-HO-, 8-H2N-, and 8-MeO-ara-cAMP derivatives). All of these doubly modified derivatives of cAMP are less than one-hundredth as active as cAMP at activating protein kinase and did not serve as substrates for the phosphodiesterase. These data show that the general inactivity of 2' derivatives of cAMP with kinase was not overcome by addition of an 8-substituent, even though many 8-substituted derivatives of cAMP activate the kinase more efficiently than does cAMP itself. In addition they show that while 2'-modification were tolerated by the phosphodiesterase, addition of an 8-substituent countermanded the allowable 2'-modification. The 8-substituted derivates of 02'-Bt-cAMP were found in general to be slightly better inhibitors of phosphodiesterase than the parent compounds containing no o2'-Bt substitution. As a group, the 8-substituted ara-cAMP derivatives were poorer inhibitors of phosphodiesterase than 8-substituted cAMP derivatives while the 8,2'-anhydro-cAMP derivatives were much poorer inhibitors than the 8-substituted ara-cAMP derivatives.", "contents": "8-Substituted derivatives of adenosine 3',5'-cyclic phosphate require an unsubstituted 2'-hydroxyl group in the ribo configuration for biological activity. Derivatives of adenosine 3',5'-cyclic phosphate (cAMP) with modifications in both the 2' and the 8 positions were synthesized and their enzymic activities as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterases were determined. Three types of derivatives were investigated: 8-substituted derivatives of O2'-Bt-cAMP, 8-substituted derivatives of 9-beta-D-arabinofuranosyladenine 3',5'-cyclic phosphate (ara-cAMP), and 8-substituted derivatives of 8,2'-anhydro-9-beta-D-arabinofuranosyladenine 3,'5'-cyclic phosphate (8,2'-anhydro-cAMP). The 8-substituted O2'-Bt-cAMP derivatives were synthesized by acylation of the preformed 8-substituted cAMP (8-HS-cAMP, 8-MeS-cAMP, and 8-PhCH2S-cAMP). 8-Br-O2'-tosyl-cAMP was sued as an intermediate for the preparation of 8,2'-anhydro-cAMP derivatives (8-HO-, 8-SH-, 8-H2N-, and 8-H3 CHN derivatives of 8,2'-anhydro-cAMP). 8-Substituted ara-cAMP derivatives were obtained by ring opening of 8-HO-8,2'-anhydro-cAMP with H+/H2O, NH3/MeOH, or MeONa/MeOH (to yield the 8-HO-, 8-H2N-, and 8-MeO-ara-cAMP derivatives). All of these doubly modified derivatives of cAMP are less than one-hundredth as active as cAMP at activating protein kinase and did not serve as substrates for the phosphodiesterase. These data show that the general inactivity of 2' derivatives of cAMP with kinase was not overcome by addition of an 8-substituent, even though many 8-substituted derivatives of cAMP activate the kinase more efficiently than does cAMP itself. In addition they show that while 2'-modification were tolerated by the phosphodiesterase, addition of an 8-substituent countermanded the allowable 2'-modification. The 8-substituted derivates of 02'-Bt-cAMP were found in general to be slightly better inhibitors of phosphodiesterase than the parent compounds containing no o2'-Bt substitution. As a group, the 8-substituted ara-cAMP derivatives were poorer inhibitors of phosphodiesterase than 8-substituted cAMP derivatives while the 8,2'-anhydro-cAMP derivatives were much poorer inhibitors than the 8-substituted ara-cAMP derivatives."} {"id": "PMID:170959", "title": "Conformational and functional studies of chemically modified cytochrome c: nitrated and iodinated cytochromes c.", "content": "The purification of iodinated (E. B. McGowan and E. Stellwagen (1970), Biochemistry 9, 3074) and of nitrated (M. Sokolovsky et al. (1970), Biochemistry 9, 5113) cytochromes c resulted in the recovery from the former preparation of diiododityrosyl-cytochrome c (DIDT-) with modification of Tyr-67 and Tyr-74, and, from the latter, a mononitromonotyrosyl-cytochrome c (MNMT-), with modification of Tyr-67, and mononitrodityrosyl-cytochrome c (MNDT-), with the added modification of Tyr-48. The three purified preparations were conformationally characterized using pH-spectroscopy, circular dichroism, thermal denaturation, reducibility with ascorbate, autoxidation with molecular oxygen, and binding with CO. These results are related to the two aspects of biological function, reducibility, measured by NADH-cytochrome c reductase, and oxidizability, with cytochrome c oxidase, as well as to structure-function relationships in the protein. MNMT-cytochrome c was found to be, structurally and conformationally, a single isomer, reducible with ascorbate, with a small, but definite affinity for both oxidation with molecular oxygen and binding of CO. Conformationally, in both valence states of the metal atom, it represents a molecular form with native-like conformation with small but definite perturbations in the immediate vicinity of the heme group, reflected by the destabilization of the Met-80-S-Fe linkage. MNMT-ferricytochrome c exhibits a pK of 6.2 for the transformation of the low-spin, native-like spectral form II containing the 695-nm band to form lacking lacking the 695-nm band. The isomerization at pK = 6.2, when analyzed in terms of the isomerization of the native protein with a pK of 9.2 and the nature of the group involved, indicates that Tyr-67 is not involved in the isomerization of the modified preparation, and possibly not in the native protein as well. In terms of biological function, the partial derangement of redecibility (24%) and the unaltered oxidizability point to the functional significance of Tyr-67, and provide another example of selectivity between the two aspects of physiological functional function, in agreement with the two-function, two-path operational model of the protein. The MNDT- and DIDT-ferricytochromes c exhibited physicochemical properties indicative of gross derangement of both the conformation of the protein as well as of the coordination configuration of the metal atom. The complete inability to accept an electron from NADH-cytochrome c reductase in both cases, and the retention of 50% of the oxidizability property of DIDT-cytochrome c, were interpreted to be the result of conformational derangement, rather than the added modification of Tyr-48 or of Tyr-74.", "contents": "Conformational and functional studies of chemically modified cytochrome c: nitrated and iodinated cytochromes c. The purification of iodinated (E. B. McGowan and E. Stellwagen (1970), Biochemistry 9, 3074) and of nitrated (M. Sokolovsky et al. (1970), Biochemistry 9, 5113) cytochromes c resulted in the recovery from the former preparation of diiododityrosyl-cytochrome c (DIDT-) with modification of Tyr-67 and Tyr-74, and, from the latter, a mononitromonotyrosyl-cytochrome c (MNMT-), with modification of Tyr-67, and mononitrodityrosyl-cytochrome c (MNDT-), with the added modification of Tyr-48. The three purified preparations were conformationally characterized using pH-spectroscopy, circular dichroism, thermal denaturation, reducibility with ascorbate, autoxidation with molecular oxygen, and binding with CO. These results are related to the two aspects of biological function, reducibility, measured by NADH-cytochrome c reductase, and oxidizability, with cytochrome c oxidase, as well as to structure-function relationships in the protein. MNMT-cytochrome c was found to be, structurally and conformationally, a single isomer, reducible with ascorbate, with a small, but definite affinity for both oxidation with molecular oxygen and binding of CO. Conformationally, in both valence states of the metal atom, it represents a molecular form with native-like conformation with small but definite perturbations in the immediate vicinity of the heme group, reflected by the destabilization of the Met-80-S-Fe linkage. MNMT-ferricytochrome c exhibits a pK of 6.2 for the transformation of the low-spin, native-like spectral form II containing the 695-nm band to form lacking lacking the 695-nm band. The isomerization at pK = 6.2, when analyzed in terms of the isomerization of the native protein with a pK of 9.2 and the nature of the group involved, indicates that Tyr-67 is not involved in the isomerization of the modified preparation, and possibly not in the native protein as well. In terms of biological function, the partial derangement of redecibility (24%) and the unaltered oxidizability point to the functional significance of Tyr-67, and provide another example of selectivity between the two aspects of physiological functional function, in agreement with the two-function, two-path operational model of the protein. The MNDT- and DIDT-ferricytochromes c exhibited physicochemical properties indicative of gross derangement of both the conformation of the protein as well as of the coordination configuration of the metal atom. The complete inability to accept an electron from NADH-cytochrome c reductase in both cases, and the retention of 50% of the oxidizability property of DIDT-cytochrome c, were interpreted to be the result of conformational derangement, rather than the added modification of Tyr-48 or of Tyr-74."} {"id": "PMID:170960", "title": "Conformational flexibility of luteinizing hormone-releasing hormone in aqueous solution. A carbon-13 spin-lattice relaxation time study.", "content": "The carbon-13 nuclear magnetic resonance (13C NMR) spectra of luteinizing hormone-releasing hormone (LH-RH) and lower homologous peptides have been assigned in aqueous solutions at various pH values. 13C spin-lattice relaxation times (T1) have been measured for all proton-bearing carbons at 25.2 and 67.9 MHz. From the T1 data the rates of overall molecular motion and intramolecular motion of side chains have been estimated. LH-RH is a flexible molecule in solution, having segmental motion along the backbone as well as in the nonaromatic side chains.", "contents": "Conformational flexibility of luteinizing hormone-releasing hormone in aqueous solution. A carbon-13 spin-lattice relaxation time study. The carbon-13 nuclear magnetic resonance (13C NMR) spectra of luteinizing hormone-releasing hormone (LH-RH) and lower homologous peptides have been assigned in aqueous solutions at various pH values. 13C spin-lattice relaxation times (T1) have been measured for all proton-bearing carbons at 25.2 and 67.9 MHz. From the T1 data the rates of overall molecular motion and intramolecular motion of side chains have been estimated. LH-RH is a flexible molecule in solution, having segmental motion along the backbone as well as in the nonaromatic side chains."} {"id": "PMID:170961", "title": "Electrophoretic mobilities of RNA tumor viruses. Studies by Doppler-shifted light scattering spectroscopy.", "content": "We have used laser beat frequency light scattering spectroscopy to measure, at several pH values, the electrophoretic mobilities of purified avian myeloblastosis (AMV), murine leukemia (MuLV), murine mammary tumor (MuMTV), and feline leukemia (FeLV) viruses. The mobilities of these viruses are similar at pH greater than or equal to7 (-2.7 to -3.2 X 10(-4) (cm/sec)/(V/cm). The isoelectric points of MuLV and AMV are apparently less than pH 3, whereas for FeLV the data could be interpreted to indicate an isoelectric point between 3 and 5. Using a Debye-H\u00fcckel model to describe the interaction between electrolytes and virus, we show that our values for the mobility of MuMTV, obtained in ionic strength 0.005, are consistent with the values of Sarkar et al. ((1973), Cancer Res. 33, 2283), obtained in ionic strength of 0.10. This model is then used to calculate surface charge densities. In terms of the density of charged groups, the RNA tumor virus envelope is not very different from the erythrocyte membrane.", "contents": "Electrophoretic mobilities of RNA tumor viruses. Studies by Doppler-shifted light scattering spectroscopy. We have used laser beat frequency light scattering spectroscopy to measure, at several pH values, the electrophoretic mobilities of purified avian myeloblastosis (AMV), murine leukemia (MuLV), murine mammary tumor (MuMTV), and feline leukemia (FeLV) viruses. The mobilities of these viruses are similar at pH greater than or equal to7 (-2.7 to -3.2 X 10(-4) (cm/sec)/(V/cm). The isoelectric points of MuLV and AMV are apparently less than pH 3, whereas for FeLV the data could be interpreted to indicate an isoelectric point between 3 and 5. Using a Debye-H\u00fcckel model to describe the interaction between electrolytes and virus, we show that our values for the mobility of MuMTV, obtained in ionic strength 0.005, are consistent with the values of Sarkar et al. ((1973), Cancer Res. 33, 2283), obtained in ionic strength of 0.10. This model is then used to calculate surface charge densities. In terms of the density of charged groups, the RNA tumor virus envelope is not very different from the erythrocyte membrane."} {"id": "PMID:170962", "title": "Isolation and characterization of the testosterone-estradiol-binding globulin from human plasma. Use of a novel affinity column.", "content": "This report concerns the purification and characterization of the testosterone-estradiol-binding globulin (TeBG) from human plasma. Cohn fraction IV was submitted sequentially to ammonium sulfate preciptation, affinity chromatography, gel filtration, and isoelectric focusing. The final product was homogeneous in polyacrylamide gel electrophoresis and sodium dodecyl sulfate gel electrophoresis. Its activity was demonstrated by the finding of slightly more than one binding site/mole for dihydrotestosterone. Association constants (M-1) at 4 and 37degreesC were ascertained for three steroids: dihydrotestosterone; 2.4 x 10(9) and 0.99 x 10(9); testosterone, 1.1 x 10(9) and 0.35 x 10(9); estradiol, 0.60 x 10(9) and 0.22 x 10(9). TeBG is a glycoprotein having a molecular weight of 94000 and both the amino acid and carbohydrate content are presented along with other physical properties.", "contents": "Isolation and characterization of the testosterone-estradiol-binding globulin from human plasma. Use of a novel affinity column. This report concerns the purification and characterization of the testosterone-estradiol-binding globulin (TeBG) from human plasma. Cohn fraction IV was submitted sequentially to ammonium sulfate preciptation, affinity chromatography, gel filtration, and isoelectric focusing. The final product was homogeneous in polyacrylamide gel electrophoresis and sodium dodecyl sulfate gel electrophoresis. Its activity was demonstrated by the finding of slightly more than one binding site/mole for dihydrotestosterone. Association constants (M-1) at 4 and 37degreesC were ascertained for three steroids: dihydrotestosterone; 2.4 x 10(9) and 0.99 x 10(9); testosterone, 1.1 x 10(9) and 0.35 x 10(9); estradiol, 0.60 x 10(9) and 0.22 x 10(9). TeBG is a glycoprotein having a molecular weight of 94000 and both the amino acid and carbohydrate content are presented along with other physical properties."} {"id": "PMID:170963", "title": "Manganese (II) And spin-labeled uridine 5'-diphosphate binding to bovine galactosyltransferase.", "content": "The kinetically observed Mn(II) activation as well as inhibition has been clarified for bovine galactosyltransferase. An electron spin resonance (ESR) titration of MnCl2 with galactosyltransferase alone at pH 8.0 clearly shows the existence of at least two metal ion binding sites with microscopic dissociation constants of 0.84 +/- 0.1 and 9.0 +/- 1.0 mM, respectively. The second site corresponds with either published kinetic constant for Mn(II) of 8.5 mM (inhibition) or 3.40 mM (activation). The contribution of the binary complex Mn(II)-UDPGal is of lesser significance, as concluded by its ESR measured Kdiss of 14.5 +/- 1.1 mM at pH 8.0. A spin-labeled inhibitor analog of UDPgalactose, UDP-4-O-(2,2,6,6-tetramethyl-4-piperidinyl-1-oxy), or UDP-R, was synthesized as a competitive inhibitor for UDPGal. It was shown from inhibition kinetics to be almost as potent an inhibitor as UDPGlu. The Ki values at pH 8.0 in the N-acetyllactosamine and lactose reactions were 0.38 +/- 0.04 and 0.63 +/- 0.06 mM, respectively, as compared with 0.10 +/- 0.01 and 0.094 +/- 0.009 mM for UDPGlu. An ESR titration of UDP-R with galactosyltransferase at pH 8.0 yielded direct physical dissociation constants of 0.40 +/- 0.07 and 0.53 +/- 0.08 mM in the absence and presence of alpha-lactalbumin, respectively. No other substrates (glucose of N-acetylglucosamine) nor Mn(II) were present.", "contents": "Manganese (II) And spin-labeled uridine 5'-diphosphate binding to bovine galactosyltransferase. The kinetically observed Mn(II) activation as well as inhibition has been clarified for bovine galactosyltransferase. An electron spin resonance (ESR) titration of MnCl2 with galactosyltransferase alone at pH 8.0 clearly shows the existence of at least two metal ion binding sites with microscopic dissociation constants of 0.84 +/- 0.1 and 9.0 +/- 1.0 mM, respectively. The second site corresponds with either published kinetic constant for Mn(II) of 8.5 mM (inhibition) or 3.40 mM (activation). The contribution of the binary complex Mn(II)-UDPGal is of lesser significance, as concluded by its ESR measured Kdiss of 14.5 +/- 1.1 mM at pH 8.0. A spin-labeled inhibitor analog of UDPgalactose, UDP-4-O-(2,2,6,6-tetramethyl-4-piperidinyl-1-oxy), or UDP-R, was synthesized as a competitive inhibitor for UDPGal. It was shown from inhibition kinetics to be almost as potent an inhibitor as UDPGlu. The Ki values at pH 8.0 in the N-acetyllactosamine and lactose reactions were 0.38 +/- 0.04 and 0.63 +/- 0.06 mM, respectively, as compared with 0.10 +/- 0.01 and 0.094 +/- 0.009 mM for UDPGlu. An ESR titration of UDP-R with galactosyltransferase at pH 8.0 yielded direct physical dissociation constants of 0.40 +/- 0.07 and 0.53 +/- 0.08 mM in the absence and presence of alpha-lactalbumin, respectively. No other substrates (glucose of N-acetylglucosamine) nor Mn(II) were present."} {"id": "PMID:170964", "title": "Hydrolysis of phosphonate esters catalyzed by 5'-nucleotide phosphodiesterase.", "content": "4-Nitrophenyl and 2-napthyl monoesters of phenylphosphonic acid have been synthesized, and an enzyme catalyzing their hydrolysis was resolved from alkaline phosphatase of a commerical calf intestinal alkaline phosphatase preparation by extensive ion-exchange chromatography, chromatography on L-phenylalanyl-Sepharose with a decreasing gradient of (NH4) 2SO4, and gel filtration. Detergent-solubilized enzyme from fresh bovine intestine was purified after (NH4)2SO4 fractionation by the same technique. The purified enzyme is homogeneous by polyacrylamide gel electrophoresis and sedimentation equilibrium centrifugation. It has a molecular weight of 108,000, contains approximately 21% carbohydrate, and has an amino acid composition considerably different from that reported from alkaline phosphatase from the same tissue. The homogeneous intestinal enzyme, an efficient catalyst of phosphonate ester hydoolysis but not of phosphate monoester hydrolysis, was identified as a 5'-nucleotide phosphodiesterase by its ability to hydrolyze 4-nitrophenyl esters of 5'-TMP but not of 3'-TMP. Also consistent with this identification was the ability of the enzyme to hydrolyze 5'-ATP to 5'-AMP and PPi, NAD+ to 5'-AMP and NMN, TpT to 5'-TMP and thymidine, pApApApA to 5'-AMP, and only the single-stranded portion of tRNA from the 3'-OH end. Snake venom 5'-nucleotide phosphodiesterase also hydrolyzes phosphonate esters, but 3'-nucleotide phosphodiesterase of spleen and cyclic 3',5'-AMP phosphodiesterase do not. Thus, types of phosphodiesterases can be conveniently distinguished by their ability to hydrolyze phosphonate esters. As substrates for 5'-nucleotide phosphodiesterases, phosphonate esters are preferable to the more conventional esters of nucleotides and bis(4-nitrophenyl) phosphate because of their superior stability and ease of synthesis. Furthermore, the rate of hydrolysis of phosphonate esters under saturating conditions is greater than that of the conventional substrates. At substrate concentrations of 1 mM the rates of hydrolysis of phosphonate esters and of nucleotide esters are comparable and both superior to that of bis(4-nitrophenyl) phosphate.", "contents": "Hydrolysis of phosphonate esters catalyzed by 5'-nucleotide phosphodiesterase. 4-Nitrophenyl and 2-napthyl monoesters of phenylphosphonic acid have been synthesized, and an enzyme catalyzing their hydrolysis was resolved from alkaline phosphatase of a commerical calf intestinal alkaline phosphatase preparation by extensive ion-exchange chromatography, chromatography on L-phenylalanyl-Sepharose with a decreasing gradient of (NH4) 2SO4, and gel filtration. Detergent-solubilized enzyme from fresh bovine intestine was purified after (NH4)2SO4 fractionation by the same technique. The purified enzyme is homogeneous by polyacrylamide gel electrophoresis and sedimentation equilibrium centrifugation. It has a molecular weight of 108,000, contains approximately 21% carbohydrate, and has an amino acid composition considerably different from that reported from alkaline phosphatase from the same tissue. The homogeneous intestinal enzyme, an efficient catalyst of phosphonate ester hydoolysis but not of phosphate monoester hydrolysis, was identified as a 5'-nucleotide phosphodiesterase by its ability to hydrolyze 4-nitrophenyl esters of 5'-TMP but not of 3'-TMP. Also consistent with this identification was the ability of the enzyme to hydrolyze 5'-ATP to 5'-AMP and PPi, NAD+ to 5'-AMP and NMN, TpT to 5'-TMP and thymidine, pApApApA to 5'-AMP, and only the single-stranded portion of tRNA from the 3'-OH end. Snake venom 5'-nucleotide phosphodiesterase also hydrolyzes phosphonate esters, but 3'-nucleotide phosphodiesterase of spleen and cyclic 3',5'-AMP phosphodiesterase do not. Thus, types of phosphodiesterases can be conveniently distinguished by their ability to hydrolyze phosphonate esters. As substrates for 5'-nucleotide phosphodiesterases, phosphonate esters are preferable to the more conventional esters of nucleotides and bis(4-nitrophenyl) phosphate because of their superior stability and ease of synthesis. Furthermore, the rate of hydrolysis of phosphonate esters under saturating conditions is greater than that of the conventional substrates. At substrate concentrations of 1 mM the rates of hydrolysis of phosphonate esters and of nucleotide esters are comparable and both superior to that of bis(4-nitrophenyl) phosphate."} {"id": "PMID:170965", "title": "31 P nuclear magnetic resonance studies of the interaction of pyridine nucleotide coenzymes with dehydrogenases.", "content": "31P nuclear magnetic resonance spectra of the pyrophosphate group in NAD+ and NADH were recorded in the presence of beef heart lactate dehydrogenase and rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. At high lactate dehydrogenase concentrations (60 mg/ml), two NADH resonances are observed: a slowly exchanging peak which is shifted to 1.9 ppm downfield (relative to free NADH) and a rapidly exchanging peak with a downfield shift of 0.5-0.6 ppm. At lover concentrations (15 mg/ml) only the rapidly exchanging peak is observed thus indicating that the peak observed at-1.9 ppm is due to coenzyme bound to an aggregated enzyme species. With NAD+, rapid exchange and downfield shifts are observed at both enzyme and concentrations, with shifts of about 1.5 ppm and 0.6 ppm at 60 and 15 mg/ml, respectively. In the presence of glyceraldehydephosphate dehydrogenase, the results are independent of enzyme concentration, and slow exchange and upfield shifts of 0.4-0.6 ppm occur with each coenzyme. These data indicate that the environment of the pyrophosphate group of oxidized and reduced coenzyme is the same for a given dehydrogenase, but is different in one enzyme from the other. The resonances observed with glyceraldehydephosphate dehydrogenase are broader than those observed with lactate dehydrogenase. This is indicative of either shorter relaxation times with the former enzyme, or the presence of multiple, unresolved resonances.", "contents": "31 P nuclear magnetic resonance studies of the interaction of pyridine nucleotide coenzymes with dehydrogenases. 31P nuclear magnetic resonance spectra of the pyrophosphate group in NAD+ and NADH were recorded in the presence of beef heart lactate dehydrogenase and rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. At high lactate dehydrogenase concentrations (60 mg/ml), two NADH resonances are observed: a slowly exchanging peak which is shifted to 1.9 ppm downfield (relative to free NADH) and a rapidly exchanging peak with a downfield shift of 0.5-0.6 ppm. At lover concentrations (15 mg/ml) only the rapidly exchanging peak is observed thus indicating that the peak observed at-1.9 ppm is due to coenzyme bound to an aggregated enzyme species. With NAD+, rapid exchange and downfield shifts are observed at both enzyme and concentrations, with shifts of about 1.5 ppm and 0.6 ppm at 60 and 15 mg/ml, respectively. In the presence of glyceraldehydephosphate dehydrogenase, the results are independent of enzyme concentration, and slow exchange and upfield shifts of 0.4-0.6 ppm occur with each coenzyme. These data indicate that the environment of the pyrophosphate group of oxidized and reduced coenzyme is the same for a given dehydrogenase, but is different in one enzyme from the other. The resonances observed with glyceraldehydephosphate dehydrogenase are broader than those observed with lactate dehydrogenase. This is indicative of either shorter relaxation times with the former enzyme, or the presence of multiple, unresolved resonances."} {"id": "PMID:170966", "title": "Polypeptide composition of cell membranes from chick embryo fibroblasts transformed by rous sarcoma virus.", "content": "Chick embryo fibroblasts were transformed by the Bryan high-titer strain of Rous sarcoma virus (RSV-BH), or a mutant (RSV-BH-Ta) inducing temperature-dependent transformation. Surface membranes from normal and transformed cells were isolated as membrane vesicles by differential centrifugation, and as cell ghosts after ZnCl2 treatment and separation in an aqueous two-phase system. These preparations were analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate or phenol/urea/acetic acid. In general a greater resolution of individual bands was found in gels containing phenol/urea/acetic acid, which separates polypeptides on the bases of size and charge. Electrophoresis of preparations from nontransformed cells showed that two polypeptides (molecular weights 200 000 and 250 000) found in cell ghosts were missing in membrane vesicles. In cell ghosts, transformation by RSV-BH resulted in a significant decrease of the 250 000 molecular weight complex. Also a polypeptide (molecular weight 73 000) prominent in membrane vesicles from nontransformed cells was decreased in transformed cells. Surfaces from cells transformed by RSV-BH-Ta at 37 degrees C presented patterns similar to those for RSV-BH infected cells. Shifting these cells to 41 degrees C resulted in an increase in the 250 000 molecular weight complex, although the amount of this protein(s) never reached that found in noninfected cells. Inhibitors of RNA and protein synthesis failed to block the morphological changes occurring in RSV-BH-Ta cells after temperature shifts from 41 degrees C to 37 degrees C or vice-versa. The same inhibitors caused a reduction in the levels of the 250 000 molecular weight complex at both temperatures. These data indicate that these large membrane-associated polypeptides play little or no role in the morphological changes associated with transformation and its reversal.", "contents": "Polypeptide composition of cell membranes from chick embryo fibroblasts transformed by rous sarcoma virus. Chick embryo fibroblasts were transformed by the Bryan high-titer strain of Rous sarcoma virus (RSV-BH), or a mutant (RSV-BH-Ta) inducing temperature-dependent transformation. Surface membranes from normal and transformed cells were isolated as membrane vesicles by differential centrifugation, and as cell ghosts after ZnCl2 treatment and separation in an aqueous two-phase system. These preparations were analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate or phenol/urea/acetic acid. In general a greater resolution of individual bands was found in gels containing phenol/urea/acetic acid, which separates polypeptides on the bases of size and charge. Electrophoresis of preparations from nontransformed cells showed that two polypeptides (molecular weights 200 000 and 250 000) found in cell ghosts were missing in membrane vesicles. In cell ghosts, transformation by RSV-BH resulted in a significant decrease of the 250 000 molecular weight complex. Also a polypeptide (molecular weight 73 000) prominent in membrane vesicles from nontransformed cells was decreased in transformed cells. Surfaces from cells transformed by RSV-BH-Ta at 37 degrees C presented patterns similar to those for RSV-BH infected cells. Shifting these cells to 41 degrees C resulted in an increase in the 250 000 molecular weight complex, although the amount of this protein(s) never reached that found in noninfected cells. Inhibitors of RNA and protein synthesis failed to block the morphological changes occurring in RSV-BH-Ta cells after temperature shifts from 41 degrees C to 37 degrees C or vice-versa. The same inhibitors caused a reduction in the levels of the 250 000 molecular weight complex at both temperatures. These data indicate that these large membrane-associated polypeptides play little or no role in the morphological changes associated with transformation and its reversal."} {"id": "PMID:170967", "title": "The interaction of nitric oxide with ascorbate oxidase.", "content": "1. The reaction of nitric oxide with oxidized and reduced ascorbate oxidase (L-ascorbate: oxygen oxidoreductase, EC 1.10.3.3) has been investigated by optical absorption measurements and electron paramagnetic resonance, and the results are compared with those of ceruloplasmin. 2. Upon anaerobic incubation of oxidized ascorbate oxidase with nitric oxide a decrease of the absorbance at 610 nm is found, which is due to an electron transfer from nitric oxide to Type-1 copper. 3. In the presence of nitric oxide the EPR absorbance of ascorbate oxidase decreases and shows predominatly a signal with characteristics of Type-2 copper (g parallel = 2.248; A parallel = 188 G), whereas the type-1 copper signal has vanished. 4. Comparison of the intensities of the EPR signals before and after NO-treatment points to the presence of one Type-2 and three Type-1 copper atoms per molecule of ascorbate oxidase. 5. It is shown that the changes in the optical and the EPR spectrum of ascorbate oxidase induced by nitric oxide are reversible. No difference in enzymic activity is found between the native enzyme and the NO-treated enzyme after removal of nitric oxide.", "contents": "The interaction of nitric oxide with ascorbate oxidase. 1. The reaction of nitric oxide with oxidized and reduced ascorbate oxidase (L-ascorbate: oxygen oxidoreductase, EC 1.10.3.3) has been investigated by optical absorption measurements and electron paramagnetic resonance, and the results are compared with those of ceruloplasmin. 2. Upon anaerobic incubation of oxidized ascorbate oxidase with nitric oxide a decrease of the absorbance at 610 nm is found, which is due to an electron transfer from nitric oxide to Type-1 copper. 3. In the presence of nitric oxide the EPR absorbance of ascorbate oxidase decreases and shows predominatly a signal with characteristics of Type-2 copper (g parallel = 2.248; A parallel = 188 G), whereas the type-1 copper signal has vanished. 4. Comparison of the intensities of the EPR signals before and after NO-treatment points to the presence of one Type-2 and three Type-1 copper atoms per molecule of ascorbate oxidase. 5. It is shown that the changes in the optical and the EPR spectrum of ascorbate oxidase induced by nitric oxide are reversible. No difference in enzymic activity is found between the native enzyme and the NO-treated enzyme after removal of nitric oxide."} {"id": "PMID:170968", "title": "Regulation of platelet phosphorylase.", "content": "A sensitive fluorimetric enzyme assay was developed for study of activation of glycogen phosphorylase (EC 2.4.1.1) in intact platelets and in platelet extracts. Activity was calculated as AMP independent (activity in the absence of AMP), total (activity in the presence of 1 mM AMP), and AMP dependent (difference between AMP independent and total). The following observations were made with intact rat platelets. (1) Stimulation of platelets with thrombin caused a 7-fold increase in total activity, with increases in both AMP-dependent and AMP-independent activities. Maximum activation was obtained within 10 s after addition of thrombin. (2) The divalent cation ionophore A23187 caused a similar, though less pronounced, activation of phosphorylase. (3) Acceleration of glycogenolysis by inhibition of respiration with cyanide caused similar changes in phosphorylase activity but with the maximum effect observed only after 45 s. (4) Dibutyryl cyclic AMP had two effects; it partially activated phosphorylase and blocked further activation by thrombin, but not A23187. Similar effects were observed with human platelets, but low resting levels of phosphorylase activity could not be maintained so that changes were not as large as with rat platelets. Experiments with extracts of rat platelets gave the following results. (1) Phosphorylase activity in many extracts of non-stimulated platelets could be increased by incubation with Mg2+-ATP and Ca2+; ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) partially inhibited. (2) In some extracts there was essentially no activation by incubation with Mg2+-ATP and Ca2+, but addition of cyclic AMP GAVE PARTIAL ACTIVATIon while addition of rabbit muscle phosphorylase kinase gave full activation. (3) Incubation of extracts of thrombin-stimulated platelets caused conversion of AMP-dependent to AMP-indeptndent activity. It is concluded that platelet phosphorylase exists in an inactive and two active forms. Conversion of the inactive to the active forms and of the AMP-dependent to the AMP-independent form is catalyzed by a kinase(s) that requires Ca2+ for full activity and is activated through a cyclic AMP-mediated process. The major change following physiological stimulation is an increase in both active forms, with little change in their ratio.", "contents": "Regulation of platelet phosphorylase. A sensitive fluorimetric enzyme assay was developed for study of activation of glycogen phosphorylase (EC 2.4.1.1) in intact platelets and in platelet extracts. Activity was calculated as AMP independent (activity in the absence of AMP), total (activity in the presence of 1 mM AMP), and AMP dependent (difference between AMP independent and total). The following observations were made with intact rat platelets. (1) Stimulation of platelets with thrombin caused a 7-fold increase in total activity, with increases in both AMP-dependent and AMP-independent activities. Maximum activation was obtained within 10 s after addition of thrombin. (2) The divalent cation ionophore A23187 caused a similar, though less pronounced, activation of phosphorylase. (3) Acceleration of glycogenolysis by inhibition of respiration with cyanide caused similar changes in phosphorylase activity but with the maximum effect observed only after 45 s. (4) Dibutyryl cyclic AMP had two effects; it partially activated phosphorylase and blocked further activation by thrombin, but not A23187. Similar effects were observed with human platelets, but low resting levels of phosphorylase activity could not be maintained so that changes were not as large as with rat platelets. Experiments with extracts of rat platelets gave the following results. (1) Phosphorylase activity in many extracts of non-stimulated platelets could be increased by incubation with Mg2+-ATP and Ca2+; ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) partially inhibited. (2) In some extracts there was essentially no activation by incubation with Mg2+-ATP and Ca2+, but addition of cyclic AMP GAVE PARTIAL ACTIVATIon while addition of rabbit muscle phosphorylase kinase gave full activation. (3) Incubation of extracts of thrombin-stimulated platelets caused conversion of AMP-dependent to AMP-indeptndent activity. It is concluded that platelet phosphorylase exists in an inactive and two active forms. Conversion of the inactive to the active forms and of the AMP-dependent to the AMP-independent form is catalyzed by a kinase(s) that requires Ca2+ for full activity and is activated through a cyclic AMP-mediated process. The major change following physiological stimulation is an increase in both active forms, with little change in their ratio."} {"id": "PMID:170969", "title": "Aspartokinase isoenzymes of the fruiting myxobacterium Myxoccus xanthus.", "content": "Two isoenzymes of aspartokinase can be found in extracts of the differentiating bacterium Myxococcus xanthus. Aspartokinase I is repressed by L-lysine and feedback is inhibited by meso-diaminopimelate and by low concentrations of L-lysine. However, the inhibition by L-lysine is no longer observed at high concentration of this amino acid. Aspartokinase II is repressed and feedback inhibited specifically by L-threonine. Both enzymes are stimulated significantly by L-methionine and L-isoleucine; the effect is greater with aspartokinase I. The role of these enzymes in relation to growth conditions of the organism is discussed and a correlation with life cycle activity is indicated.", "contents": "Aspartokinase isoenzymes of the fruiting myxobacterium Myxoccus xanthus. Two isoenzymes of aspartokinase can be found in extracts of the differentiating bacterium Myxococcus xanthus. Aspartokinase I is repressed by L-lysine and feedback is inhibited by meso-diaminopimelate and by low concentrations of L-lysine. However, the inhibition by L-lysine is no longer observed at high concentration of this amino acid. Aspartokinase II is repressed and feedback inhibited specifically by L-threonine. Both enzymes are stimulated significantly by L-methionine and L-isoleucine; the effect is greater with aspartokinase I. The role of these enzymes in relation to growth conditions of the organism is discussed and a correlation with life cycle activity is indicated."} {"id": "PMID:170970", "title": "Multiple thermal discontinuities in glucose-6-phosphatase activity.", "content": "The temperature dependence of glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase EC 3.1.3.9) was studied in rat liver and kidney microsomal fractions. Arrhenius plots were non-linear and showed four distinct discontinuities in enzyme activity over the temperature range 2-41 degrees C. The discontinuities occurred at approx. 39, 30, 20 and 12 degrees C in the liver and were similar to this in the kidney. Changes in the energy of activation for the enzyme were noted at approx. 20 degrees C in both tissues. The multiple discontinuities in glucose-6-phosphatase activity are viewed as a reflection of complex reorganization and/or change in physical state of the membrane components, primarily lipid.", "contents": "Multiple thermal discontinuities in glucose-6-phosphatase activity. The temperature dependence of glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase EC 3.1.3.9) was studied in rat liver and kidney microsomal fractions. Arrhenius plots were non-linear and showed four distinct discontinuities in enzyme activity over the temperature range 2-41 degrees C. The discontinuities occurred at approx. 39, 30, 20 and 12 degrees C in the liver and were similar to this in the kidney. Changes in the energy of activation for the enzyme were noted at approx. 20 degrees C in both tissues. The multiple discontinuities in glucose-6-phosphatase activity are viewed as a reflection of complex reorganization and/or change in physical state of the membrane components, primarily lipid."} {"id": "PMID:170971", "title": "Cyclic nucleotide phosphodiesterase of retinal photoreceptors. Partial purification and some properties of the enzyme.", "content": "1. A cyclic nucleotide phosphodiesterase (EC 3.1.4.16) has been partially purified from bovine rod outer segments. The enzyme preparation obtained has a very high specific activity towards cyclic GMP and is still able to hydrolyze cyclic AMP. Upon polyacrylamide gel electrophoresis, one major and three minor protein bands are seen, the enzyme activity being associated with the major band. The enzyme eluted from the gels still hydrolyzes both cyclic nucleotides. At all substrate concentrations tested, cyclic GMP was hydrolyzed at a faster rate. The enzyme eluted from the gel columns migrated as a single band upon electrophoresis in 0.1% sodium dodecyl sulfate-polyacrylamide gels corresponding to a molecular weight of 105 000. 2. A complex kinetic pattern was observed for cyclic GMP hydrolysis: the plot of velocity vs substrate concentration was hyperbolic at low and sigmoidal at higher concentrations. By contrast, simple kinetics were observed for cyclic AMP hydrolysis yielding an apparent Km of 0.1 mM. The unusual kinetics may be implicated in the regulation of cyclic GMP levels in rod outer segments. 3. Cyclic AMP stimulated the hydrolysis of cyclic GMP at low and inhibited it at higher concentrations. Addition of Mg2+ appeared to be necessary for optimum activity. The activity measured in the absence of exogenous Mg2+ was abolished by EDTA.", "contents": "Cyclic nucleotide phosphodiesterase of retinal photoreceptors. Partial purification and some properties of the enzyme. 1. A cyclic nucleotide phosphodiesterase (EC 3.1.4.16) has been partially purified from bovine rod outer segments. The enzyme preparation obtained has a very high specific activity towards cyclic GMP and is still able to hydrolyze cyclic AMP. Upon polyacrylamide gel electrophoresis, one major and three minor protein bands are seen, the enzyme activity being associated with the major band. The enzyme eluted from the gels still hydrolyzes both cyclic nucleotides. At all substrate concentrations tested, cyclic GMP was hydrolyzed at a faster rate. The enzyme eluted from the gel columns migrated as a single band upon electrophoresis in 0.1% sodium dodecyl sulfate-polyacrylamide gels corresponding to a molecular weight of 105 000. 2. A complex kinetic pattern was observed for cyclic GMP hydrolysis: the plot of velocity vs substrate concentration was hyperbolic at low and sigmoidal at higher concentrations. By contrast, simple kinetics were observed for cyclic AMP hydrolysis yielding an apparent Km of 0.1 mM. The unusual kinetics may be implicated in the regulation of cyclic GMP levels in rod outer segments. 3. Cyclic AMP stimulated the hydrolysis of cyclic GMP at low and inhibited it at higher concentrations. Addition of Mg2+ appeared to be necessary for optimum activity. The activity measured in the absence of exogenous Mg2+ was abolished by EDTA."} {"id": "PMID:170972", "title": "Cyclic nucleotide phosphodiesterases associated with bovine retinal outer-segment fragments.", "content": "ATP-dependent cyclic GMP phosphodiesterase activity (EC 3.1.4.16) associated with bovine retinal outer-segment fragment preparations was stimulated an order of magnitude by light, confirming the results of Miki et al. (1973) Proc. Natl. Acad. Sci. U.S. 70, 3820-3824 at Yale for the frog system. In contrast to the results of the Yale group, however, light stimulation was not observed for cyclic AMP as substrate. A direct relationship of bovine rhodopsin bleaching to phosphodiesterase activation differs from a previous report by the Yale group that full activation of the frog enzyme was achieved by bleaching of a maximum of 2% rhodopsin. Phosphodiesterase activity could be qualitatively removed from the fresh outer-segment preparations with isotonic sucrose which apparently did not disrupt the plasmalemma or discs. Activity recovered from the washing was not light sensitive. Two Km values were determined for cyclic AMP, 5 and 0.05 mM; for cyclic GMP a Km of 0.22 mM was found. All Km values were determined in the presence of 1 mM ATP in the dark. Sonication of fresh outer segments or storing at -20 degrees C abolished the light response. However, storage at -76 degrees C fully preserved it.", "contents": "Cyclic nucleotide phosphodiesterases associated with bovine retinal outer-segment fragments. ATP-dependent cyclic GMP phosphodiesterase activity (EC 3.1.4.16) associated with bovine retinal outer-segment fragment preparations was stimulated an order of magnitude by light, confirming the results of Miki et al. (1973) Proc. Natl. Acad. Sci. U.S. 70, 3820-3824 at Yale for the frog system. In contrast to the results of the Yale group, however, light stimulation was not observed for cyclic AMP as substrate. A direct relationship of bovine rhodopsin bleaching to phosphodiesterase activation differs from a previous report by the Yale group that full activation of the frog enzyme was achieved by bleaching of a maximum of 2% rhodopsin. Phosphodiesterase activity could be qualitatively removed from the fresh outer-segment preparations with isotonic sucrose which apparently did not disrupt the plasmalemma or discs. Activity recovered from the washing was not light sensitive. Two Km values were determined for cyclic AMP, 5 and 0.05 mM; for cyclic GMP a Km of 0.22 mM was found. All Km values were determined in the presence of 1 mM ATP in the dark. Sonication of fresh outer segments or storing at -20 degrees C abolished the light response. However, storage at -76 degrees C fully preserved it."} {"id": "PMID:170973", "title": "Classification of fructose-1,6-bisphosphate aldolases based on 18O retention in the cleavage reaction.", "content": "Oxygen (18) was used as a mechanistic probe in the investigation of several different sources of fructose 1,6-bisphosphate aldolases (EC 4.1.2.13) which, due to differences in some physical and chemical properties, could not be clearly put in either Class I or Class II. Aldolases may be identified as belonging to a particular class on the basis of the amount of 180 retained in the dihydroxyacetone phosphate produced in the cleavage of [2-Oxygen (18)] fructose 1,6-biphosphate. The mechanism of Class I aldolases involves an obligatory exchange of the C-2 oxygen atom of fructose 1,6-bisphosphate, leading to the absence of 180 in the product. For Class II aldolases, the C-2 oxygen atom is retained in the aldol cleavage reaction. Aldolases from spinach and L. casei base intermediate. Aldosase from C. perfringens was found to be Class II, suggesting a metal-chelate intermediate. Results with Euglena aldolase confirmed that this organism contained both types of aldolases with approximately 78% Class II. The data show that despite a wide variety of physical and chemical properties, there are important mechanistic similarities within each class of enzyme and significant differences between the two classes. The determination of 180 retention in the product of the cleavage reaction using [2-180] fructose 1,6-biphosphate is an accurate means of classifying these enzymes since it is a measure of a property which is directly related to the mechanisms of the reactions.", "contents": "Classification of fructose-1,6-bisphosphate aldolases based on 18O retention in the cleavage reaction. Oxygen (18) was used as a mechanistic probe in the investigation of several different sources of fructose 1,6-bisphosphate aldolases (EC 4.1.2.13) which, due to differences in some physical and chemical properties, could not be clearly put in either Class I or Class II. Aldolases may be identified as belonging to a particular class on the basis of the amount of 180 retained in the dihydroxyacetone phosphate produced in the cleavage of [2-Oxygen (18)] fructose 1,6-biphosphate. The mechanism of Class I aldolases involves an obligatory exchange of the C-2 oxygen atom of fructose 1,6-bisphosphate, leading to the absence of 180 in the product. For Class II aldolases, the C-2 oxygen atom is retained in the aldol cleavage reaction. Aldolases from spinach and L. casei base intermediate. Aldosase from C. perfringens was found to be Class II, suggesting a metal-chelate intermediate. Results with Euglena aldolase confirmed that this organism contained both types of aldolases with approximately 78% Class II. The data show that despite a wide variety of physical and chemical properties, there are important mechanistic similarities within each class of enzyme and significant differences between the two classes. The determination of 180 retention in the product of the cleavage reaction using [2-180] fructose 1,6-biphosphate is an accurate means of classifying these enzymes since it is a measure of a property which is directly related to the mechanisms of the reactions."} {"id": "PMID:170974", "title": "Formation of adenosine 3',5'-monophosphate from adenosine in mouse thymocytes.", "content": "The effect of adenosine on the mouse thymocyte adenylate cyclase-adenosine 3':5'-monophosphate (cyclic AMP) system was examined. Adenosine, like prostaglandin E1, can cause 5-fold or greater increases in thymocyte cyclic AMP content in the presence but not in the absence of certain cyclic phosphodiesterase inhibitors. Two non-methylxanthine inhibitors potentiated the prostaglandin E1 and adenosine responses, while methylxanthines selectively inhibited the adenosine response. Adenosine increased cyclic AMP content significantly within 1 min and was maximal by 10 to 20 min with approx. 2 and 10 muM adenosine being minimal and half-maximal effective doses, respectively. Combinations of prostaglandin E1, isoproterenol and adenosine were near additive and not synergistic. Of the adenosine analogues tested, only 2-chloro- and 2-fluoroadenosine significantly increased cyclic AMP. Thymocytes prelabeled with [14C]adenine exhibited dramatic increases in cyclic [14C]AMP 10 min after addition of adenosine or prostaglandin E1 which corresponded to simultaneously determined increases in total cyclic AMP. Using [14C]adenosine, the percent of total cyclic AMP increase due to adenosine was only 16%. Adenosine was also shown to elicit a 40% increase in particulate thymocyte adenylate cyclase activity. Therefore, the increased content of cyclic AMP seen in mouse thymocytes after incubation with adenosine was due primarily to stimulation of adenylate cyclase and only partially to conversion of adenosine to cyclic AMP. The increased cellular content of cyclic AMP may be, in part, responsible for various immunosuppressive effects of adenosine.", "contents": "Formation of adenosine 3',5'-monophosphate from adenosine in mouse thymocytes. The effect of adenosine on the mouse thymocyte adenylate cyclase-adenosine 3':5'-monophosphate (cyclic AMP) system was examined. Adenosine, like prostaglandin E1, can cause 5-fold or greater increases in thymocyte cyclic AMP content in the presence but not in the absence of certain cyclic phosphodiesterase inhibitors. Two non-methylxanthine inhibitors potentiated the prostaglandin E1 and adenosine responses, while methylxanthines selectively inhibited the adenosine response. Adenosine increased cyclic AMP content significantly within 1 min and was maximal by 10 to 20 min with approx. 2 and 10 muM adenosine being minimal and half-maximal effective doses, respectively. Combinations of prostaglandin E1, isoproterenol and adenosine were near additive and not synergistic. Of the adenosine analogues tested, only 2-chloro- and 2-fluoroadenosine significantly increased cyclic AMP. Thymocytes prelabeled with [14C]adenine exhibited dramatic increases in cyclic [14C]AMP 10 min after addition of adenosine or prostaglandin E1 which corresponded to simultaneously determined increases in total cyclic AMP. Using [14C]adenosine, the percent of total cyclic AMP increase due to adenosine was only 16%. Adenosine was also shown to elicit a 40% increase in particulate thymocyte adenylate cyclase activity. Therefore, the increased content of cyclic AMP seen in mouse thymocytes after incubation with adenosine was due primarily to stimulation of adenylate cyclase and only partially to conversion of adenosine to cyclic AMP. The increased cellular content of cyclic AMP may be, in part, responsible for various immunosuppressive effects of adenosine."} {"id": "PMID:170975", "title": "On the mechanism of action of cholera toxin on isolated rat adrenocortical cells. Comparison with the effects of adrenocorticotropin on steroidogenesis and cyclic AMP output.", "content": "The effects of cholera toxin on isolated rat adrenocortical cells have been investigated. Both steroid and cyclic AMP output from adrenal cells were increased by the toxin in a dose dependent fashion. The concentration of toxin for half maximal stimulation for both of these responses was about 40 ng/ml. Maximal steroidogenesis and cyclic AMP output was obtained with similar concentrations of the toxin. A correlation was observed between the low amounts of cyclic AMP produced in response to all doses of cholera toxin and to physiologically significant concentrations of adrenocorticotropin (ACTH) (less than 0.1 munit/ml; i.e. submaximal for steroidogenesis in this system). This was in direct contrast to the much higher levels of cyclic AMP generated by concentrations of ACTH greater than 1 munits/ml. Time course studies demonstrated a time-lag between toxin addition and steroid response of at least 40 min. Binding of cholera toxin to adrenal cells was rapid and was 90% complete within 15 min at both 37 and 0 degrees C. These data indicate that most of the delay in response to cholera toxin is due to processes subsequent to the initial binding interaction. Following the initial delay the subsequent maximal rate of steroidogenesis brought about by cholera toxin was very similar to that obtained with a concentration of ACTH that was maximal for steroidogenesis. Significant increases in cyclic AMP levels were detected about 20 min before increased steroidogenesis was apparent. Possible explanations for this result are considered. The results presented indicate great potential use for cholera toxin in the study of adrenal steroidogenic control mechanisms, particularly at the level of receptor mechanisms and the role of cyclic AMP.", "contents": "On the mechanism of action of cholera toxin on isolated rat adrenocortical cells. Comparison with the effects of adrenocorticotropin on steroidogenesis and cyclic AMP output. The effects of cholera toxin on isolated rat adrenocortical cells have been investigated. Both steroid and cyclic AMP output from adrenal cells were increased by the toxin in a dose dependent fashion. The concentration of toxin for half maximal stimulation for both of these responses was about 40 ng/ml. Maximal steroidogenesis and cyclic AMP output was obtained with similar concentrations of the toxin. A correlation was observed between the low amounts of cyclic AMP produced in response to all doses of cholera toxin and to physiologically significant concentrations of adrenocorticotropin (ACTH) (less than 0.1 munit/ml; i.e. submaximal for steroidogenesis in this system). This was in direct contrast to the much higher levels of cyclic AMP generated by concentrations of ACTH greater than 1 munits/ml. Time course studies demonstrated a time-lag between toxin addition and steroid response of at least 40 min. Binding of cholera toxin to adrenal cells was rapid and was 90% complete within 15 min at both 37 and 0 degrees C. These data indicate that most of the delay in response to cholera toxin is due to processes subsequent to the initial binding interaction. Following the initial delay the subsequent maximal rate of steroidogenesis brought about by cholera toxin was very similar to that obtained with a concentration of ACTH that was maximal for steroidogenesis. Significant increases in cyclic AMP levels were detected about 20 min before increased steroidogenesis was apparent. Possible explanations for this result are considered. The results presented indicate great potential use for cholera toxin in the study of adrenal steroidogenic control mechanisms, particularly at the level of receptor mechanisms and the role of cyclic AMP."} {"id": "PMID:170976", "title": "Prostaglandin E1 induced changes in cyclic AMP levels in WI-38 human fibroblasts. Two different effects of cell density.", "content": "WI-38 lung diploid fibroblasts respond to protaglandin E1 with increased levels of cyclic adenosine 3':5'-monophosphate. This increase is affected by cell density in two ways: (a) The initial rate of accumulation of intracellular cyclic AMP increases with increasing cell density. (b) However, the elevated levels of cyclic AMP are more stably maintained in lower-density cells, and this stability decreases with increasing cell density. Cyclic AMP phosphodiesterase activities, as well as the efflux of intracellular cyclic AMP into the medium are similar at all cell densities.", "contents": "Prostaglandin E1 induced changes in cyclic AMP levels in WI-38 human fibroblasts. Two different effects of cell density. WI-38 lung diploid fibroblasts respond to protaglandin E1 with increased levels of cyclic adenosine 3':5'-monophosphate. This increase is affected by cell density in two ways: (a) The initial rate of accumulation of intracellular cyclic AMP increases with increasing cell density. (b) However, the elevated levels of cyclic AMP are more stably maintained in lower-density cells, and this stability decreases with increasing cell density. Cyclic AMP phosphodiesterase activities, as well as the efflux of intracellular cyclic AMP into the medium are similar at all cell densities."} {"id": "PMID:170977", "title": "Effect of calcium(ion) uptake by rat adrenal mitochondria on pregnenolone formation and spectral properties of cytochrome P-450.", "content": "The effect of calcium on pregnenolone formation from endogenous precursors has been studied in mitochondria from rat decapsulated and capsular adrenal glands. In the presence of succinate, addition of calcium chloride in the concentration range 20-150 muM caused an inhibition of pregnenolone formation in both decapsulated and capsular adrenal mitochondria. 11beta-hydroxylation of added deoxycosticosterone in decapsulated adrenal mitochondria was also inhibited. Under these conditions, calcium inhibited the reduction of adrenodoxin, a component of the cytochrome P-450 reductase system, presumably because uptake of calcium by the mitochondria competes with energy-linked transhydrogenase for high-energy intermediates. For this reason, incubations were carried out in the presence of succinate plus isocitrate plus NADP+. Under these conditions, calcium chloride in the concentration range 120-875 muM caused a 2-4-fold stimulation of pregnenolone formation, but had no effect on corticosterone formation from added deoxycorticosterone. The effect of calcium on the optical spectra of cytochrome P-450 has also been examined in mitochondria from decapsulated and capsular rat adrenals. In the presence of succinate, calcium induced a spectral change resembling a type I difference spectrum of cytochrome P-450. Thus it appears that uptake of calcium by adrenal mitochondria can stimulate pregnenolone formation by increasing the interaction of mitochondrial cytochrome P-450 with endogenous substrate.", "contents": "Effect of calcium(ion) uptake by rat adrenal mitochondria on pregnenolone formation and spectral properties of cytochrome P-450. The effect of calcium on pregnenolone formation from endogenous precursors has been studied in mitochondria from rat decapsulated and capsular adrenal glands. In the presence of succinate, addition of calcium chloride in the concentration range 20-150 muM caused an inhibition of pregnenolone formation in both decapsulated and capsular adrenal mitochondria. 11beta-hydroxylation of added deoxycosticosterone in decapsulated adrenal mitochondria was also inhibited. Under these conditions, calcium inhibited the reduction of adrenodoxin, a component of the cytochrome P-450 reductase system, presumably because uptake of calcium by the mitochondria competes with energy-linked transhydrogenase for high-energy intermediates. For this reason, incubations were carried out in the presence of succinate plus isocitrate plus NADP+. Under these conditions, calcium chloride in the concentration range 120-875 muM caused a 2-4-fold stimulation of pregnenolone formation, but had no effect on corticosterone formation from added deoxycorticosterone. The effect of calcium on the optical spectra of cytochrome P-450 has also been examined in mitochondria from decapsulated and capsular rat adrenals. In the presence of succinate, calcium induced a spectral change resembling a type I difference spectrum of cytochrome P-450. Thus it appears that uptake of calcium by adrenal mitochondria can stimulate pregnenolone formation by increasing the interaction of mitochondrial cytochrome P-450 with endogenous substrate."} {"id": "PMID:170978", "title": "An adenosine 3',5'-monophosphate-requiring mutant of the luminous bacteria Beneckea harveyi.", "content": "We have isolated a mutant of the luminous bacterium Beneckea harveyi, which requires exogenous adenosine 3',5'-monophosphate (cyclic AMP) to synthesize luciferase and emit light. The mutant was pleiotropic, lacking not only the ability to luminesce, but also the capacities to form flagella and the ability to utilize a variety of carbohydrates for growth. All these deficiencies could be corrected by added cyclic AMP. The cyclic AMP-induced de novo synthesis of luciferase was possible only after autoinduction had occurred. The induction time by cyclic AMP ranged between 6 and 10 min at 27 degrees C.", "contents": "An adenosine 3',5'-monophosphate-requiring mutant of the luminous bacteria Beneckea harveyi. We have isolated a mutant of the luminous bacterium Beneckea harveyi, which requires exogenous adenosine 3',5'-monophosphate (cyclic AMP) to synthesize luciferase and emit light. The mutant was pleiotropic, lacking not only the ability to luminesce, but also the capacities to form flagella and the ability to utilize a variety of carbohydrates for growth. All these deficiencies could be corrected by added cyclic AMP. The cyclic AMP-induced de novo synthesis of luciferase was possible only after autoinduction had occurred. The induction time by cyclic AMP ranged between 6 and 10 min at 27 degrees C."} {"id": "PMID:170979", "title": "Phosphonopyruvic acid: A probable precursor of phosphonic acids in cell-free preparation of Tetrahymena.", "content": "1. In cell-free preparations of Tetrahymena, doubly labelled [32P]phosphoenol-[3-14C]pyruvate gives rise to 2-aminoethylphosphonate and 2-amino-3-phosphonopropionate, labelled with the two isotopes in the same ratio as the starting compound. The result is consistent with an intra-molecular rearrangement of phosphoenolpyruvate in the biosynthetic sequence of carbon-phosphorus bond formation. 2. Incubation of [32P]phosphoenolpyruvate with the same preparation, followed by treatment with 2,4-dinitrophenylhydrazine, yielded labelled hydrazones. When these were subjected to hydrogenolysis, the radioactivity was recovered in 2-aminoethylphosphonate and 2-amino-3-phosphonopropionate, suggesting that 2-phosphonoacetaldehyde and 3-phosphonopyruvic acid were probable precursors of the aminoalkylphosphonic acids. 3. Radioactivity from 2-amino-3-phosphono-[3-14C]propionic acid was incorporated into 2-aminoethylphosphonic acid, but incorporation of the radioactivity into lipids was negligible.", "contents": "Phosphonopyruvic acid: A probable precursor of phosphonic acids in cell-free preparation of Tetrahymena. 1. In cell-free preparations of Tetrahymena, doubly labelled [32P]phosphoenol-[3-14C]pyruvate gives rise to 2-aminoethylphosphonate and 2-amino-3-phosphonopropionate, labelled with the two isotopes in the same ratio as the starting compound. The result is consistent with an intra-molecular rearrangement of phosphoenolpyruvate in the biosynthetic sequence of carbon-phosphorus bond formation. 2. Incubation of [32P]phosphoenolpyruvate with the same preparation, followed by treatment with 2,4-dinitrophenylhydrazine, yielded labelled hydrazones. When these were subjected to hydrogenolysis, the radioactivity was recovered in 2-aminoethylphosphonate and 2-amino-3-phosphonopropionate, suggesting that 2-phosphonoacetaldehyde and 3-phosphonopyruvic acid were probable precursors of the aminoalkylphosphonic acids. 3. Radioactivity from 2-amino-3-phosphono-[3-14C]propionic acid was incorporated into 2-aminoethylphosphonic acid, but incorporation of the radioactivity into lipids was negligible."} {"id": "PMID:170980", "title": "Induced changes in the electron paramagnetic resonance spectra of mammalian catalases.", "content": "The EPR spectra of bovine liver catalase, rat liver catalase and human erythrocyte catalase have been measured at 9.0 degrees K. In N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES) and Tris buffers at pH 7.0, the liver catalases show EPR spectra typical of rhombically distorted high spin ferric heme with major lines at g = 6.50, 5.35, 1.98. A number of extra lines are also seen; these are weak or absent in human erythrocyte catalase. The effect of the addition of formate, nitrite, acetate, fluoride, azide, hypophosphite and of inactivation with 3-amino-1,2,4-triazole on the degree of rhombic distortion has been studied. There is a good correlation between the low temperature EPR and room temperature optical changes for the binding of formic acid in HEPES and Tris. There is no evidence from EPR spectra for the presence of heme-heme interactions in the binding of formic acid to human erythrocyte catalase. The properties of catalase are altered in phosphate and in distilled water. This is a consequence of the low temperature of measurement.", "contents": "Induced changes in the electron paramagnetic resonance spectra of mammalian catalases. The EPR spectra of bovine liver catalase, rat liver catalase and human erythrocyte catalase have been measured at 9.0 degrees K. In N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES) and Tris buffers at pH 7.0, the liver catalases show EPR spectra typical of rhombically distorted high spin ferric heme with major lines at g = 6.50, 5.35, 1.98. A number of extra lines are also seen; these are weak or absent in human erythrocyte catalase. The effect of the addition of formate, nitrite, acetate, fluoride, azide, hypophosphite and of inactivation with 3-amino-1,2,4-triazole on the degree of rhombic distortion has been studied. There is a good correlation between the low temperature EPR and room temperature optical changes for the binding of formic acid in HEPES and Tris. There is no evidence from EPR spectra for the presence of heme-heme interactions in the binding of formic acid to human erythrocyte catalase. The properties of catalase are altered in phosphate and in distilled water. This is a consequence of the low temperature of measurement."} {"id": "PMID:170981", "title": "Electron paramagnetic resonance spectra of catalase in mammalian tissues.", "content": "The relatively small number of paramagnetic species and the high concentration of catalase in mammalian liver and blood make it possible to directly study this enzyme in frozen whole tissue. The EPR spectra of catalase are dependent on the heme environment and in human blood only catalase A, gxy = 6.48, 5.36 is observed whereas in liver a second spectrum, catalase B, gxy = 6.80, 5.07 can also be seen. Using rapid freeze techniques it has been shown that in rat liver catalase A corresponds to the in vivo steady state and that after death this is largely converted into catalase B. Data from the perfusion of rat livers with oxygenated and deoxygenated blood and dextran solutions together with results from in vitro studies of catalase are interpreted as indicating that catalase B results from the interaction of catalase with an organic acid, most probably formic acid, that the acid is a peroxidative substrate for catalase in vivo and that peroxidation of the acid is not the major role for catalase in rat liver. Catalase binding with other small molecules in intact liver has been demonstrated by perfusion with nitrite-containing dextrans and by intraperitoneal injection of 3-amino-1,2,4-triazole.", "contents": "Electron paramagnetic resonance spectra of catalase in mammalian tissues. The relatively small number of paramagnetic species and the high concentration of catalase in mammalian liver and blood make it possible to directly study this enzyme in frozen whole tissue. The EPR spectra of catalase are dependent on the heme environment and in human blood only catalase A, gxy = 6.48, 5.36 is observed whereas in liver a second spectrum, catalase B, gxy = 6.80, 5.07 can also be seen. Using rapid freeze techniques it has been shown that in rat liver catalase A corresponds to the in vivo steady state and that after death this is largely converted into catalase B. Data from the perfusion of rat livers with oxygenated and deoxygenated blood and dextran solutions together with results from in vitro studies of catalase are interpreted as indicating that catalase B results from the interaction of catalase with an organic acid, most probably formic acid, that the acid is a peroxidative substrate for catalase in vivo and that peroxidation of the acid is not the major role for catalase in rat liver. Catalase binding with other small molecules in intact liver has been demonstrated by perfusion with nitrite-containing dextrans and by intraperitoneal injection of 3-amino-1,2,4-triazole."} {"id": "PMID:170982", "title": "Magnetic studies of the four-iron high-potential, non-heme protein from Chromatium vinosum.", "content": "Extensive EPR studies on high-potential, iron-sulfur protein from Chromatium vinosum indicate that the singular spectrum of this four-iron, non-heme protein consists of a superposition of three distinct signals; namely, two principal signals of equal weight, one reflecting axial and the other rhombic symmetry, and a third nearly isotropic minority component. In addition, magnetic susceptibility experiments on two oxidation states of the protein from 4.2 to approx. 260 degrees K indicate antiferromagnetic exchange coupling between iron atoms. Possible origins of the complex EPR signals are discussed, and a preferred model that is consistent with EPR, magnetic susceptibility, NMR, X-ray, and M\u00f6ssbauer data is presented.", "contents": "Magnetic studies of the four-iron high-potential, non-heme protein from Chromatium vinosum. Extensive EPR studies on high-potential, iron-sulfur protein from Chromatium vinosum indicate that the singular spectrum of this four-iron, non-heme protein consists of a superposition of three distinct signals; namely, two principal signals of equal weight, one reflecting axial and the other rhombic symmetry, and a third nearly isotropic minority component. In addition, magnetic susceptibility experiments on two oxidation states of the protein from 4.2 to approx. 260 degrees K indicate antiferromagnetic exchange coupling between iron atoms. Possible origins of the complex EPR signals are discussed, and a preferred model that is consistent with EPR, magnetic susceptibility, NMR, X-ray, and M\u00f6ssbauer data is presented."} {"id": "PMID:170983", "title": "Characterization of the respiratory nitrate reductase of Klebsiella aerogenes as a molybdenum-containing iron-sulfur enzyme.", "content": "1. In respiratory nitrate reductase I of Klebsiella aerogenes, 0.24 atom of molybdenum, eight iron-sulfur groups and four tightly bound, non-heme iron atoms per molecule of enzyme (Mr 260 000) are found. 2. EPR spectra at 83 degrees K of oxidized and reduced nitrate reductase I show complex lines at g = 2.02 and g = 1.98, which are more intense in the reduced than in the oxidized enzyme. The resonances, the shape and intensity of which are rather temperature insensitive, are attributed to two species of paramagnetic molybdenum. In dithionite-reduced enzyme all these lines are saturated at the same microwave power of 15 mW. This is not the case in oxidized enzyme, where the resonance at g = 2.02 is hard to saturate. Addition of nitrate to dithionite-reduced reductase I decreases the intensity of the EPR lines to about that of oxidized enzyme. The participation of molybdenum in the electron transfer process has been discussed. 3. At 18 degrees K the oxidized enzyme exhibits an axial-symmetrical signal with g parallel = 2.10 and g = 2.03, and a signal with unknown symmetry at g = 2.015. Upon reduction by dithionite, a ferredoxin type of signal is observed with g values at 2.05, 1.95 and 1.88, while the g = 2.015 signal disappears. Reoxidation by nitrate causes a concomitant disappearance of the ferredoxin type of signal and reappearance of the g = 2.015 signal; hence iron-sulfur centres participate in the transfer of electrons to nitrate. 4. Nitrate reductase II, containing only two (Mr 117 000 and 57 000) of the three subunits found in nitrate reductase I and lacking the tightly bound iron, does not exhibit the axial-symmetrical signal (g = 2.10 and 2.03). Thus, it suggested that this signal in nitrate reductase I stems from an iron centre in the low-molecular weight subunit (Mr 52 000). 5. Inhibition studies confirm the participation of metals in the transfer of electrons from reduced benzylviologen to nitrate and show that the binding sites for these substrates are different.", "contents": "Characterization of the respiratory nitrate reductase of Klebsiella aerogenes as a molybdenum-containing iron-sulfur enzyme. 1. In respiratory nitrate reductase I of Klebsiella aerogenes, 0.24 atom of molybdenum, eight iron-sulfur groups and four tightly bound, non-heme iron atoms per molecule of enzyme (Mr 260 000) are found. 2. EPR spectra at 83 degrees K of oxidized and reduced nitrate reductase I show complex lines at g = 2.02 and g = 1.98, which are more intense in the reduced than in the oxidized enzyme. The resonances, the shape and intensity of which are rather temperature insensitive, are attributed to two species of paramagnetic molybdenum. In dithionite-reduced enzyme all these lines are saturated at the same microwave power of 15 mW. This is not the case in oxidized enzyme, where the resonance at g = 2.02 is hard to saturate. Addition of nitrate to dithionite-reduced reductase I decreases the intensity of the EPR lines to about that of oxidized enzyme. The participation of molybdenum in the electron transfer process has been discussed. 3. At 18 degrees K the oxidized enzyme exhibits an axial-symmetrical signal with g parallel = 2.10 and g = 2.03, and a signal with unknown symmetry at g = 2.015. Upon reduction by dithionite, a ferredoxin type of signal is observed with g values at 2.05, 1.95 and 1.88, while the g = 2.015 signal disappears. Reoxidation by nitrate causes a concomitant disappearance of the ferredoxin type of signal and reappearance of the g = 2.015 signal; hence iron-sulfur centres participate in the transfer of electrons to nitrate. 4. Nitrate reductase II, containing only two (Mr 117 000 and 57 000) of the three subunits found in nitrate reductase I and lacking the tightly bound iron, does not exhibit the axial-symmetrical signal (g = 2.10 and 2.03). Thus, it suggested that this signal in nitrate reductase I stems from an iron centre in the low-molecular weight subunit (Mr 52 000). 5. Inhibition studies confirm the participation of metals in the transfer of electrons from reduced benzylviologen to nitrate and show that the binding sites for these substrates are different."} {"id": "PMID:170984", "title": "Preparation of lutropin with acetyl or acetimidinyl substituents on the amino groups of the beta-subunit.", "content": "The free amino groups in ovine lutropin beta subunit were acylated with acetic anhydride and methyl acetimidinate-HCl to produce the corresponding acetyl and acetimidinyl ovine lutropin beta derivative. These two derivatives recombined with ovine lutropin alpha as well as native ovine lutropin beta, but produced lutropin derivatives which were 33-50% less active than the ovine lutropin alpha + ovine lutropin beta in biological assays.", "contents": "Preparation of lutropin with acetyl or acetimidinyl substituents on the amino groups of the beta-subunit. The free amino groups in ovine lutropin beta subunit were acylated with acetic anhydride and methyl acetimidinate-HCl to produce the corresponding acetyl and acetimidinyl ovine lutropin beta derivative. These two derivatives recombined with ovine lutropin alpha as well as native ovine lutropin beta, but produced lutropin derivatives which were 33-50% less active than the ovine lutropin alpha + ovine lutropin beta in biological assays."} {"id": "PMID:170985", "title": "D-galactose accumulation in rabbit ileum. Effects of theophylline on serosal permeability.", "content": "The effects of theophylline and dibutyryl cyclic AMP, on in vitro unidirectional galactose fluxes across the mucosal and serosal borders of rabbit ileum have been studied. 1. When Ringer [galactose] = 2mM, theophylline and dibutyryl cyclic AMP reduce both mucosal-serosal and serosal-mucosal galactose flux by approx. 50%. The K1 for theophylline inhibition of flux in both directions is 2 mM. 1 mM dibutyryl cyclic AMP elicits a maximal inhibitory response. Concurrent with the inhibition in transmural galactose fluxes, theophylline and dibutyryl cyclic AMP increase the tissue accumulation of [galactose] and the specific-activity ratio R of 3H : 14C-labelled galactose coming from the mucosal and serosal solutions respectively. It is deduced that theophylline and dibutyryl cyclic AMP are without effect on the mucosal unidirectional permeability to galactose but cause a symmetrical reduction in serosal entry and exit permeability. 2. Reduction in the asymmetry of the mucosal border to galactose by reducing Ringer [Na], raising Ringer [galctose] or adding ouabain reduces the theophylline-dependent increase in galactose accumulation. 3. Hypertonicity in the serosal solution increases the permeability of the serosal border to galactose and reduces tissue galactose accumulation. Serosal hypertonicity partially reverses the theophylline-depedent effects on galactose transport. Replacing Ringer chloride by sulphate abolishes the theophylline-dependent effects on galactose transport. 4. It is considered that the theophylline-dependent increase in galactose accumulation results from the reduction in serosal permeability. This is shown to be a quantitatively consistent inference. 5. Further support for the view that the asymmetric transport of galactose in rabbit ileum results from convective-diffusion is presented.", "contents": "D-galactose accumulation in rabbit ileum. Effects of theophylline on serosal permeability. The effects of theophylline and dibutyryl cyclic AMP, on in vitro unidirectional galactose fluxes across the mucosal and serosal borders of rabbit ileum have been studied. 1. When Ringer [galactose] = 2mM, theophylline and dibutyryl cyclic AMP reduce both mucosal-serosal and serosal-mucosal galactose flux by approx. 50%. The K1 for theophylline inhibition of flux in both directions is 2 mM. 1 mM dibutyryl cyclic AMP elicits a maximal inhibitory response. Concurrent with the inhibition in transmural galactose fluxes, theophylline and dibutyryl cyclic AMP increase the tissue accumulation of [galactose] and the specific-activity ratio R of 3H : 14C-labelled galactose coming from the mucosal and serosal solutions respectively. It is deduced that theophylline and dibutyryl cyclic AMP are without effect on the mucosal unidirectional permeability to galactose but cause a symmetrical reduction in serosal entry and exit permeability. 2. Reduction in the asymmetry of the mucosal border to galactose by reducing Ringer [Na], raising Ringer [galctose] or adding ouabain reduces the theophylline-dependent increase in galactose accumulation. 3. Hypertonicity in the serosal solution increases the permeability of the serosal border to galactose and reduces tissue galactose accumulation. Serosal hypertonicity partially reverses the theophylline-depedent effects on galactose transport. Replacing Ringer chloride by sulphate abolishes the theophylline-dependent effects on galactose transport. 4. It is considered that the theophylline-dependent increase in galactose accumulation results from the reduction in serosal permeability. This is shown to be a quantitatively consistent inference. 5. Further support for the view that the asymmetric transport of galactose in rabbit ileum results from convective-diffusion is presented."} {"id": "PMID:170986", "title": "A comparison of the interfacial interactions of the apoprotein from high density lipoprotein and beta-casein with phospholipids.", "content": "The conformations adopted by beta-casein and the total apoprotein from serum high density lipoprotein when spread at the air-water interface are compared; the monolayer data are consistent with the apoprotein being alpha-helical and the beta-casein being disordered with segments distributed in loops and trains. The penetration of these hydrophobic proteins into phosphatidylcholine monolayers in different physical states was investigated. More protein can penetrate into monolayers when they are in the liquid-expanded state; for penetration at constant total surface area the lateral compressibility of the lipid is an important factor. The charge and conformation of the polar group of the phospholipid does not have a major influence on the interaction. The mixed films of lipid and protein have a mosaic structure; probably the beta-casein is in a compressed state whereas the apoprotein is extended as alpha-helices in the plane of the interface. The chain-length depedences of the interaction of the apoprotein with phosphatidylcholine monolayers and bilayers are different; when the apoprotein binds to bilayers of shorter-chain phosphatidylcholines it alters the shape of the lipid-water interface whereas with monolayers the interface remains planar throughout.", "contents": "A comparison of the interfacial interactions of the apoprotein from high density lipoprotein and beta-casein with phospholipids. The conformations adopted by beta-casein and the total apoprotein from serum high density lipoprotein when spread at the air-water interface are compared; the monolayer data are consistent with the apoprotein being alpha-helical and the beta-casein being disordered with segments distributed in loops and trains. The penetration of these hydrophobic proteins into phosphatidylcholine monolayers in different physical states was investigated. More protein can penetrate into monolayers when they are in the liquid-expanded state; for penetration at constant total surface area the lateral compressibility of the lipid is an important factor. The charge and conformation of the polar group of the phospholipid does not have a major influence on the interaction. The mixed films of lipid and protein have a mosaic structure; probably the beta-casein is in a compressed state whereas the apoprotein is extended as alpha-helices in the plane of the interface. The chain-length depedences of the interaction of the apoprotein with phosphatidylcholine monolayers and bilayers are different; when the apoprotein binds to bilayers of shorter-chain phosphatidylcholines it alters the shape of the lipid-water interface whereas with monolayers the interface remains planar throughout."} {"id": "PMID:170987", "title": "Partial purification and characterization of DNA polymerases from a Rous sarcoma virus-transformed rat cell line.", "content": "A new DNA polymerase was partially purified from cell-free extracts of a continuous rat cell-line (XC). The XC cells had been transformed by the Prague strain of Rous sarcoma virus but did not produce infectious virus. The molecular weight of the DNA polymerase is 70,000, as estimated by glycerol gradient centrifugation and by Sephadex gel filtration. This enzyme can be distinguished from the other cellular DNA polymerases by its elution pattern on DNA-cellulose column chromatography, its molecular weight, and its primer-template specificity. The enzyme has some characteristics of the murine leukemia virus reverse transcriptase. It is partially inhibited by immunoglobulin G purified from rabbit antiserum prepared against Rauscher leukemia virus reverse transcriptase, but is not inhibited by IgG from rat antiserum prepared against avian myeloblastosis virus reverse transcriptase. However, the XC cell enzyme can be distinguished from the murine leukemia virus reverse transcriptase by its inefficiency in copying an oligo(dG)12-poly(rC)primer-template.", "contents": "Partial purification and characterization of DNA polymerases from a Rous sarcoma virus-transformed rat cell line. A new DNA polymerase was partially purified from cell-free extracts of a continuous rat cell-line (XC). The XC cells had been transformed by the Prague strain of Rous sarcoma virus but did not produce infectious virus. The molecular weight of the DNA polymerase is 70,000, as estimated by glycerol gradient centrifugation and by Sephadex gel filtration. This enzyme can be distinguished from the other cellular DNA polymerases by its elution pattern on DNA-cellulose column chromatography, its molecular weight, and its primer-template specificity. The enzyme has some characteristics of the murine leukemia virus reverse transcriptase. It is partially inhibited by immunoglobulin G purified from rabbit antiserum prepared against Rauscher leukemia virus reverse transcriptase, but is not inhibited by IgG from rat antiserum prepared against avian myeloblastosis virus reverse transcriptase. However, the XC cell enzyme can be distinguished from the murine leukemia virus reverse transcriptase by its inefficiency in copying an oligo(dG)12-poly(rC)primer-template."} {"id": "PMID:170988", "title": "Nuclear phosphoprotein kinase activities in normal and neoplastic tissues.", "content": "Nuclear phosphoprotein kinases from normal rat liver and transplantable neoplasms were fractionated and compared. A phosphoprotein kinase fraction activated by Mn2+ was found to be present only in the neoplasms. This nuclear protein kinase phosphorylated nuclear proteins represented by one major and several minor bands as determined by polyacrylamide gel electrophoresis (M approximately 50,000).", "contents": "Nuclear phosphoprotein kinase activities in normal and neoplastic tissues. Nuclear phosphoprotein kinases from normal rat liver and transplantable neoplasms were fractionated and compared. A phosphoprotein kinase fraction activated by Mn2+ was found to be present only in the neoplasms. This nuclear protein kinase phosphorylated nuclear proteins represented by one major and several minor bands as determined by polyacrylamide gel electrophoresis (M approximately 50,000)."} {"id": "PMID:170989", "title": "Uptake of [3H] thymidine and cell DNA synthesis during the early multiplication phase of herpesvirus hominis in BHK cells.", "content": "Experiments about the interaction of herpes viruses with BHK-cells during the first 6 h after infection concerning uptake and incorporation of dThd have been reported. During adsorption and penetration, the inhibition of uptake and of incorporation of [3H] dThd is sensitive to heat, but not to ultraviolet irradiation or cycloheximide. The eclipse is characterized by a strongly increased uptake of [3H] dThd and by inhibition of cell DNA synthesis. Both are sensitive to ultraviolet irradiation of the particles and cycloheximid treatment of the cells. It is concluded that the events during adsorption and penetration are dependent on the particles themselves, whereas the events during the eclipse depend on the activity of the viral genome. The implications of the findings are discussed.", "contents": "Uptake of [3H] thymidine and cell DNA synthesis during the early multiplication phase of herpesvirus hominis in BHK cells. Experiments about the interaction of herpes viruses with BHK-cells during the first 6 h after infection concerning uptake and incorporation of dThd have been reported. During adsorption and penetration, the inhibition of uptake and of incorporation of [3H] dThd is sensitive to heat, but not to ultraviolet irradiation or cycloheximide. The eclipse is characterized by a strongly increased uptake of [3H] dThd and by inhibition of cell DNA synthesis. Both are sensitive to ultraviolet irradiation of the particles and cycloheximid treatment of the cells. It is concluded that the events during adsorption and penetration are dependent on the particles themselves, whereas the events during the eclipse depend on the activity of the viral genome. The implications of the findings are discussed."} {"id": "PMID:170990", "title": "Relation of cell type and cell density to the degree of post-transcriptional modification of tRNALys and tRNAPhe.", "content": "An examination of the reversed-phase chromatographic profiles of tRNALys and tRNAPhe from SV40-transformed BALB/3T3 cells grown to different cell densities, untransformed BALB/3T3 cells grown to confluency and BALB/c mouse liver indicates that with increasing cell density in culture the degree of the peroxy-Y modification in tRNAPhe and an undetermined modification in tRNALys become more like that of differentiated tissue (liver). Because precursor/product relationships appear to exist among the unmodified and modified forms of the isoaccepting species for each of these tRNAs, the present findings support the view that the often reported differences in tRNA isoaccepting spectra result primarily from differences in post-transcriptional modifications, rather than from different tRNA transcripts.", "contents": "Relation of cell type and cell density to the degree of post-transcriptional modification of tRNALys and tRNAPhe. An examination of the reversed-phase chromatographic profiles of tRNALys and tRNAPhe from SV40-transformed BALB/3T3 cells grown to different cell densities, untransformed BALB/3T3 cells grown to confluency and BALB/c mouse liver indicates that with increasing cell density in culture the degree of the peroxy-Y modification in tRNAPhe and an undetermined modification in tRNALys become more like that of differentiated tissue (liver). Because precursor/product relationships appear to exist among the unmodified and modified forms of the isoaccepting species for each of these tRNAs, the present findings support the view that the often reported differences in tRNA isoaccepting spectra result primarily from differences in post-transcriptional modifications, rather than from different tRNA transcripts."} {"id": "PMID:170991", "title": "Synthesis of viral proteins by the avian myeloblastosis viral core component.", "content": "Avian Myeloblastosis Viral (AMV) core component was isolated and shown to synthesize AMV proteins in vitro. This reaction was linearly dependent on viral core concentration, proceeded linearly with time, and was inhibited by puromycin and aurintricarboxylic acid. The proteins synthesized in vitro co-electrophoresed and co-chromatographed with known proteins, and were immunoprecipitated by total and monospecific antibodies to known AMV proteins.", "contents": "Synthesis of viral proteins by the avian myeloblastosis viral core component. Avian Myeloblastosis Viral (AMV) core component was isolated and shown to synthesize AMV proteins in vitro. This reaction was linearly dependent on viral core concentration, proceeded linearly with time, and was inhibited by puromycin and aurintricarboxylic acid. The proteins synthesized in vitro co-electrophoresed and co-chromatographed with known proteins, and were immunoprecipitated by total and monospecific antibodies to known AMV proteins."} {"id": "PMID:170992", "title": "Plasma lipoproteins in rats with experimental biliary obstruction. I. A chemical study.", "content": "Acute biliary obstruction in the rat is associated with striking alterations of the plasma level and the physico-chemical properties of plasma lipoproteins. 1. The level of very low density lipproteins (VLDL) in plasma increases from 2 to 3 fold. The chemical composition of VLDL is characterized by a high content of phospholipids and cholesterol and by a diminution of the relative content of triacylglycerols and protein. On cellulose acetate electrophoresis, VLDL show a beta-mobility. 2. The plasma concentration of low density lipoproteins (1.019--1.063 g/ml, LDL2) increases several fold above the control level. Phospholipids and unesterified cholesterol are the major components of this fraction which contains only a minute amount of cholesteryl ester (4%) and triacylglycerols (10%). LDL2 contain a component which migrates to the cathode in 1% agar gel electrophoresis. Separation of LDL2 by gel filtration on 2% agarose column results in the identification of three subfractions. Subfraction I contains a large proportion of cholesterol and triacylgylcerols, subfraction II is rich in unesterified cholesterol and phospholipids whereas subfraction III has a chemical composition fairly similar to that of the control LDL2. 3. The level of high density lipoproteins (HDL) also increases after bile duct ligation. The chemical composition of HDL2 (1.063-1.125 g/ml) is characterized by a high content of unesterified cholesterol and phospholipids and by a remarkable reduction in the content of cholesteryl esters and protein.", "contents": "Plasma lipoproteins in rats with experimental biliary obstruction. I. A chemical study. Acute biliary obstruction in the rat is associated with striking alterations of the plasma level and the physico-chemical properties of plasma lipoproteins. 1. The level of very low density lipproteins (VLDL) in plasma increases from 2 to 3 fold. The chemical composition of VLDL is characterized by a high content of phospholipids and cholesterol and by a diminution of the relative content of triacylglycerols and protein. On cellulose acetate electrophoresis, VLDL show a beta-mobility. 2. The plasma concentration of low density lipoproteins (1.019--1.063 g/ml, LDL2) increases several fold above the control level. Phospholipids and unesterified cholesterol are the major components of this fraction which contains only a minute amount of cholesteryl ester (4%) and triacylglycerols (10%). LDL2 contain a component which migrates to the cathode in 1% agar gel electrophoresis. Separation of LDL2 by gel filtration on 2% agarose column results in the identification of three subfractions. Subfraction I contains a large proportion of cholesterol and triacylgylcerols, subfraction II is rich in unesterified cholesterol and phospholipids whereas subfraction III has a chemical composition fairly similar to that of the control LDL2. 3. The level of high density lipoproteins (HDL) also increases after bile duct ligation. The chemical composition of HDL2 (1.063-1.125 g/ml) is characterized by a high content of unesterified cholesterol and phospholipids and by a remarkable reduction in the content of cholesteryl esters and protein."} {"id": "PMID:170995", "title": "Response of renal calcium-binding protein. Independence of kidney vitamin D hydroxylation.", "content": "Dietary calcium and dietary phosphorus restriction were studied in chicks fed either cholecalciferol or 1alpha-hydroxycholecalciferol. Intestinal calcium absorption and calcium-binding protein of 1alpha-hydroxycholecalciferol-treated chicks remained unchanged under dietary calcium restriction, but increased under dietary phosphorus restriction. Kidney calcium-binding protein was not altered by dietary caclium restriction in chidks treated with either cholecalciferol or 1alpha-hydroxycholecalciferol, but increased under dietary phosphorus restriction independent of the vitamin D source. In contrast to the intestine, calcium-binding activity of the kidney was found to be poorly related to the calcium-binding protein concentration. It is suggested that kidney calcium-binding protein is regulated by a mechanism different from that of intestinal calcium-binding protein, and that its concentration in renal tissue is related to renal caclium excretion or plasma calcium level.", "contents": "Response of renal calcium-binding protein. Independence of kidney vitamin D hydroxylation. Dietary calcium and dietary phosphorus restriction were studied in chicks fed either cholecalciferol or 1alpha-hydroxycholecalciferol. Intestinal calcium absorption and calcium-binding protein of 1alpha-hydroxycholecalciferol-treated chicks remained unchanged under dietary calcium restriction, but increased under dietary phosphorus restriction. Kidney calcium-binding protein was not altered by dietary caclium restriction in chidks treated with either cholecalciferol or 1alpha-hydroxycholecalciferol, but increased under dietary phosphorus restriction independent of the vitamin D source. In contrast to the intestine, calcium-binding activity of the kidney was found to be poorly related to the calcium-binding protein concentration. It is suggested that kidney calcium-binding protein is regulated by a mechanism different from that of intestinal calcium-binding protein, and that its concentration in renal tissue is related to renal caclium excretion or plasma calcium level."} {"id": "PMID:170996", "title": "The involvement of receptro sulphydryl groups in the binding of steroids to the cytoplasmic glucocorticoid receptor from rat thymus.", "content": "The glucocorticoid receptor protein present in the high-speed supernant fraction of rat thymus tissue is extremely unstable, having a half-life of about 2 h at 4 degrees C. It was found that the decline in steroid-binding capacity could be slowed, though not arrested completely, by the addition of sulphydryl-protecting agents such as 2-mercaptoethanol or dithiothreitol, and by EDTA. The inactivation was also partly reversed by these agents. 0.5 mM N-ethylmaleimideor p-chloromercuriphenylsulphonic acid inactivated the recptor at 4 degrees C, but the presence of bound steroid protected the receptor against this inactivation. Bound steroid did not protect the receptor against the action of higher concentrations of these reagents. Treatment of intact thymus cells with 2,4-dinitrophenol resulted in a reduction in the steroid-binding capacity of the supernatant fraction derived from these cells. This effect of 2,4-dinitrophenol could not be reversed by the presence of dithiothreitol in the extraction buffer. It is concluded that the inactivation of the receptor in vitro is at least partly due to the oxidation of one or more sulphydryl groups necessary for steroid binding; the process of oxidation does not account for the reduction in steroid binding observed in intact thymus cells under conditions of energy deprivation.", "contents": "The involvement of receptro sulphydryl groups in the binding of steroids to the cytoplasmic glucocorticoid receptor from rat thymus. The glucocorticoid receptor protein present in the high-speed supernant fraction of rat thymus tissue is extremely unstable, having a half-life of about 2 h at 4 degrees C. It was found that the decline in steroid-binding capacity could be slowed, though not arrested completely, by the addition of sulphydryl-protecting agents such as 2-mercaptoethanol or dithiothreitol, and by EDTA. The inactivation was also partly reversed by these agents. 0.5 mM N-ethylmaleimideor p-chloromercuriphenylsulphonic acid inactivated the recptor at 4 degrees C, but the presence of bound steroid protected the receptor against this inactivation. Bound steroid did not protect the receptor against the action of higher concentrations of these reagents. Treatment of intact thymus cells with 2,4-dinitrophenol resulted in a reduction in the steroid-binding capacity of the supernatant fraction derived from these cells. This effect of 2,4-dinitrophenol could not be reversed by the presence of dithiothreitol in the extraction buffer. It is concluded that the inactivation of the receptor in vitro is at least partly due to the oxidation of one or more sulphydryl groups necessary for steroid binding; the process of oxidation does not account for the reduction in steroid binding observed in intact thymus cells under conditions of energy deprivation."} {"id": "PMID:170998", "title": "The effects of pregnancy and lactation on the activities in rat liver of some enzymes associated with glucose metabolism.", "content": "1. The ratio of the combined activities of hexokinase (EC 2.7.1.1) and glucokinase (EC 2.7.1.2) to the activity of glucose-6-phosphatase (EC 3.1.3.9) changed in favour of the glycolytic enzymes during pregnancy and at peak lactation. 2. There were no important changes in the ratio of the activity of phosphofructokinase (EC 2.7.1.11) to that of fructose diphosphatase (EC 3.1.3.11). 3. The ratio of the activity of pyruvate kinase (EC 2.7.1.40) to the combined activities of phosphoenolpyruvate carboxylase (EE 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) changed in favour of the glycolytic enzyme during pregnancy and at peak lactation, but changed in favour of the gluconeogenic enzymes immediately after parturition. 4. These changes are considered in relation to the changes in food intake and hormonal status that occur during pregnancy and lactation.", "contents": "The effects of pregnancy and lactation on the activities in rat liver of some enzymes associated with glucose metabolism. 1. The ratio of the combined activities of hexokinase (EC 2.7.1.1) and glucokinase (EC 2.7.1.2) to the activity of glucose-6-phosphatase (EC 3.1.3.9) changed in favour of the glycolytic enzymes during pregnancy and at peak lactation. 2. There were no important changes in the ratio of the activity of phosphofructokinase (EC 2.7.1.11) to that of fructose diphosphatase (EC 3.1.3.11). 3. The ratio of the activity of pyruvate kinase (EC 2.7.1.40) to the combined activities of phosphoenolpyruvate carboxylase (EE 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) changed in favour of the glycolytic enzyme during pregnancy and at peak lactation, but changed in favour of the gluconeogenic enzymes immediately after parturition. 4. These changes are considered in relation to the changes in food intake and hormonal status that occur during pregnancy and lactation."} {"id": "PMID:171000", "title": "Implications of the reorganizational behavior of condensed phosphates for mitochondrial phosphorylation.", "content": "The composition of phosphorus-32 labeled polyphosphoric acid (32PPA) prepared from, (i) H3(32)PO4 and (82 percent w/w) P2O5 and, (ii) by incorporation of radioactivity from H3(32)PO4 into unlabeled polyphosphoric acid (PPA) was examined and found to be the same. The identity of these condensed phosphorate mixtures, as established, argues strongly in favor of a rapid and complete equilibration and provides direct evidence in support of Van Wazer's reorganization theory of condensed phosphates. No evidence for metaphosphates or label exchange in an aqueous environment was found. 32PPA was found to exist in metastable equilibrium with 32PPA as a crystalline solid of different composition. Agreement of hydrolytic rate data from the mixtures of condensed phosphates with literature values for individual species suggests that the hydrolysis of the pyro- and tripoly-phosphate species proceeds independently in the presence of other homologs. The rate of hydrolysis of the condensed phosphates (at pH5.0 and 65 degrees C) was found to be proportional to chain length, increasing about four-fold between pyro- and hexapoly-phosphate. The same correlation is also manifest in the adenosine 5' polyphosphates. A slight enhancement in the rate of hydrolysis of adenosine diphosphate, increasingly more pronounced in the case of adenosine tri- and tetra-phosphate, was also noted. This effect is attributed to the presence of the adenosine moiety. The most interesting aspect of the rate data is to be found in the similarity of the rates of hydrolysis of the adenosine 5' polyphosphates, relative to their inorganic polyphosphate counterparts. The significance of these findings is discussed and the viewpoint is presented that the properties of condensed phosphates are compatible with the requisite characteristics that must be predicated of any in situ phosphoryl precursor in mitochondrial phosphorylation.", "contents": "Implications of the reorganizational behavior of condensed phosphates for mitochondrial phosphorylation. The composition of phosphorus-32 labeled polyphosphoric acid (32PPA) prepared from, (i) H3(32)PO4 and (82 percent w/w) P2O5 and, (ii) by incorporation of radioactivity from H3(32)PO4 into unlabeled polyphosphoric acid (PPA) was examined and found to be the same. The identity of these condensed phosphorate mixtures, as established, argues strongly in favor of a rapid and complete equilibration and provides direct evidence in support of Van Wazer's reorganization theory of condensed phosphates. No evidence for metaphosphates or label exchange in an aqueous environment was found. 32PPA was found to exist in metastable equilibrium with 32PPA as a crystalline solid of different composition. Agreement of hydrolytic rate data from the mixtures of condensed phosphates with literature values for individual species suggests that the hydrolysis of the pyro- and tripoly-phosphate species proceeds independently in the presence of other homologs. The rate of hydrolysis of the condensed phosphates (at pH5.0 and 65 degrees C) was found to be proportional to chain length, increasing about four-fold between pyro- and hexapoly-phosphate. The same correlation is also manifest in the adenosine 5' polyphosphates. A slight enhancement in the rate of hydrolysis of adenosine diphosphate, increasingly more pronounced in the case of adenosine tri- and tetra-phosphate, was also noted. This effect is attributed to the presence of the adenosine moiety. The most interesting aspect of the rate data is to be found in the similarity of the rates of hydrolysis of the adenosine 5' polyphosphates, relative to their inorganic polyphosphate counterparts. The significance of these findings is discussed and the viewpoint is presented that the properties of condensed phosphates are compatible with the requisite characteristics that must be predicated of any in situ phosphoryl precursor in mitochondrial phosphorylation."} {"id": "PMID:170999", "title": "The effect of catecholamines and prostaglandins upon human and rat erythrocytes.", "content": "Both human and rat erythrocytes respond to low doses (10(-11)--10(-9) M) of L-isoproterenol and L-epinephrine with an increased degree of hypotonic hemolysis and a decreased rate of filtration through standardized paper filters. The receptors in both cell types have many of the characteristics of beta-receptors for catecholamines. However, hormone-receptor interaction in the human cell does not lead to an increase in intracellular cyclic AMP concentration, but in the rat cell, hormone-receptor interaction does lead to a significant increase in cyclic AMP content. Thus, catecholamine-beta-receptor interaction, at least in the human red cell, leads to a change in red cell properties which are not mediated by adenylate cyclase activation. Likewise, prostaglandin E2, at 10(-12)--10(-10) M, causes are increased degree of hypotonic hemolysis and a decreased rate of filtration through standardized paper filters, but it also does not increase the cycliC AMP content of the human erythrocyte but does increase that of the rat erythrocyte. Nevertheless, exogenous cyclic AMP, when added at a concentration of 10(-8) M to washed human erythrocytes, increases the degree of hypotonic hemolysis. Conversely, prostaglandin E1, at 10(-12)--10(-10) M, causes a decreased degree of hypotonic hemolysis and an increased rate of filtration through a standard filter. Both prostaglandin E2 and the catecholamines decrease the size of a rapidly exchangeable calcium pool, and prostaglandin E1 increases it.", "contents": "The effect of catecholamines and prostaglandins upon human and rat erythrocytes. Both human and rat erythrocytes respond to low doses (10(-11)--10(-9) M) of L-isoproterenol and L-epinephrine with an increased degree of hypotonic hemolysis and a decreased rate of filtration through standardized paper filters. The receptors in both cell types have many of the characteristics of beta-receptors for catecholamines. However, hormone-receptor interaction in the human cell does not lead to an increase in intracellular cyclic AMP concentration, but in the rat cell, hormone-receptor interaction does lead to a significant increase in cyclic AMP content. Thus, catecholamine-beta-receptor interaction, at least in the human red cell, leads to a change in red cell properties which are not mediated by adenylate cyclase activation. Likewise, prostaglandin E2, at 10(-12)--10(-10) M, causes are increased degree of hypotonic hemolysis and a decreased rate of filtration through standardized paper filters, but it also does not increase the cycliC AMP content of the human erythrocyte but does increase that of the rat erythrocyte. Nevertheless, exogenous cyclic AMP, when added at a concentration of 10(-8) M to washed human erythrocytes, increases the degree of hypotonic hemolysis. Conversely, prostaglandin E1, at 10(-12)--10(-10) M, causes a decreased degree of hypotonic hemolysis and an increased rate of filtration through a standard filter. Both prostaglandin E2 and the catecholamines decrease the size of a rapidly exchangeable calcium pool, and prostaglandin E1 increases it."} {"id": "PMID:171001", "title": "Enzymatic and non-enzymatic assay of superoxide dismutase.", "content": "Superoxide dismutase from breef brain and rat liver was assayed in an enzymatic system, using xanthine oxidase, and a non-enzymatic system, based on aerobic reduction of nitro-blue tetrazolium in presence of phenazine methosulphate. The non-enzymatic assay is rapid and simple and permits simulatneous analysis of many samples. Similar results are found by the two methods of assay of superoxide dismutase.", "contents": "Enzymatic and non-enzymatic assay of superoxide dismutase. Superoxide dismutase from breef brain and rat liver was assayed in an enzymatic system, using xanthine oxidase, and a non-enzymatic system, based on aerobic reduction of nitro-blue tetrazolium in presence of phenazine methosulphate. The non-enzymatic assay is rapid and simple and permits simulatneous analysis of many samples. Similar results are found by the two methods of assay of superoxide dismutase."} {"id": "PMID:171006", "title": "Desoxyribonucleic acid and pyrimidine synthesis in the rat during intra-uterine growth retardation: responsiveness of several organs.", "content": "The response of DNA synthesis, thymidine incorporation and the activities of uridine kinase, carbamyl phosphate synthetase and aspartate transcarbamylase were studied in the rat, following intra-uterine growth retardation. A good correlation was found between the falls of DNA production and thymidine incorporation and the decrease of the activity of the three enzymes during the fetal period. After birth, cell proliferation remained depressed but no further changes occurred in the enzymatic activities.", "contents": "Desoxyribonucleic acid and pyrimidine synthesis in the rat during intra-uterine growth retardation: responsiveness of several organs. The response of DNA synthesis, thymidine incorporation and the activities of uridine kinase, carbamyl phosphate synthetase and aspartate transcarbamylase were studied in the rat, following intra-uterine growth retardation. A good correlation was found between the falls of DNA production and thymidine incorporation and the decrease of the activity of the three enzymes during the fetal period. After birth, cell proliferation remained depressed but no further changes occurred in the enzymatic activities."} {"id": "PMID:171008", "title": "Neurophysiological observations in diseased newborns.", "content": "The early statements that the EEG alone could correctly be used for the assessment of gestational age (cf., among others, Dreyfus-Brisac, 1964; Parmelee et al., 1968; and Nolte et al., 1969), even in pathological babies, need some restrictive qualifications. Likewise, the more recent statements that certain neurophysiological parameters, including nerve conduction velocity and basic EEG patterns are independent not only of gestational age and body weight, but also of various abnormal factors in the pre- and perinatal periods, appear also too rigid, at least as regards the EEG and the other parameters used in this study. As a matter of fact, some authors who had adhered rather strictly to these concepts have later on presented evidence suggesting some deviations in bioelectric brain maturation in some cases, as for example, in small-for-date newborns of toxemic mothers (Schulte et al., 1972). When more exact quantification by coding techniques was applied (Parmelee et al., 1968), the conclusion was also reached that extrauterine and intrauterine development of bioelectric brain activity developed according to the conceptional age, regardless of variable extrauterine experience, although it was recognized that other categories of behavioral and neurophysiological activities, for example, Moro reflex, states stability, crying, sucking, scores, etc., are more labile to environmental and pathological factors (Prechtl et al., 1972; Michaelis et al., 1973).", "contents": "Neurophysiological observations in diseased newborns. The early statements that the EEG alone could correctly be used for the assessment of gestational age (cf., among others, Dreyfus-Brisac, 1964; Parmelee et al., 1968; and Nolte et al., 1969), even in pathological babies, need some restrictive qualifications. Likewise, the more recent statements that certain neurophysiological parameters, including nerve conduction velocity and basic EEG patterns are independent not only of gestational age and body weight, but also of various abnormal factors in the pre- and perinatal periods, appear also too rigid, at least as regards the EEG and the other parameters used in this study. As a matter of fact, some authors who had adhered rather strictly to these concepts have later on presented evidence suggesting some deviations in bioelectric brain maturation in some cases, as for example, in small-for-date newborns of toxemic mothers (Schulte et al., 1972). When more exact quantification by coding techniques was applied (Parmelee et al., 1968), the conclusion was also reached that extrauterine and intrauterine development of bioelectric brain activity developed according to the conceptional age, regardless of variable extrauterine experience, although it was recognized that other categories of behavioral and neurophysiological activities, for example, Moro reflex, states stability, crying, sucking, scores, etc., are more labile to environmental and pathological factors (Prechtl et al., 1972; Michaelis et al., 1973)."} {"id": "PMID:171009", "title": "Biorhythms in toxicology and pharmacology. I. Generalities, ultradian and circadian biorhythms.", "content": "According to their periods, rhythms can be classified in ultradian (period inferior to one day), circadian (period equal to one day) and infradian (period superior to one day). Different biorhythms of endogenous origin are modified mostly relatively to their amplitude by definite doses of the effects of pharmacological or toxic agents. Circadian variations of the effects of drugs, of the toxicities of gases as well as circadian modifications of the reactions to different stresses and agressions have been demonstrated amply in animals (mostly nocturnal rodents) and sometimes in man. In a general way reactions are more rapid and more marked in the active period where enzymatic reactions show a peak activity corresponding to a maximal energy output than during the rest and sleep periods.", "contents": "Biorhythms in toxicology and pharmacology. I. Generalities, ultradian and circadian biorhythms. According to their periods, rhythms can be classified in ultradian (period inferior to one day), circadian (period equal to one day) and infradian (period superior to one day). Different biorhythms of endogenous origin are modified mostly relatively to their amplitude by definite doses of the effects of pharmacological or toxic agents. Circadian variations of the effects of drugs, of the toxicities of gases as well as circadian modifications of the reactions to different stresses and agressions have been demonstrated amply in animals (mostly nocturnal rodents) and sometimes in man. In a general way reactions are more rapid and more marked in the active period where enzymatic reactions show a peak activity corresponding to a maximal energy output than during the rest and sleep periods."} {"id": "PMID:171012", "title": "Stimulation by organic solvents and detergents of conversion of L-sorbose to L-sorbosone by Gluconobacter melanogenus IFO 3293.", "content": "Treatment of Gluconobacter melanogenus IFO 3293 cells with benzene, carbon tetrachloride, cyclohexane, deoxycholate, toluene, or xylene stimulated their conversion of L-sorbose to L-sorbosone two- to threefold. The degree of stimulation depended upon the length of exposure time to the agent and the age of the G. melanogenus cells. A rapid decrease in viability of the cells and degradation of cell RNA was noted after treatment with the effective agents. The G. melanogenus cells were unable to absorb L-sorbose actively after toluene treatment.", "contents": "Stimulation by organic solvents and detergents of conversion of L-sorbose to L-sorbosone by Gluconobacter melanogenus IFO 3293. Treatment of Gluconobacter melanogenus IFO 3293 cells with benzene, carbon tetrachloride, cyclohexane, deoxycholate, toluene, or xylene stimulated their conversion of L-sorbose to L-sorbosone two- to threefold. The degree of stimulation depended upon the length of exposure time to the agent and the age of the G. melanogenus cells. A rapid decrease in viability of the cells and degradation of cell RNA was noted after treatment with the effective agents. The G. melanogenus cells were unable to absorb L-sorbose actively after toluene treatment."} {"id": "PMID:171014", "title": "[Effect of triftazin on the transmission of excitation in the brain of the rabbit under the prolonged administration of the preparation].", "content": "Experiments were conducted on awake rabbits to which trifluoperazine was given daily for 2 weeks in a dose of 1 mg/kg a day; a study was made of the reaction of the cortical neurones in response to the electrostimulation of its adjacent areas. In measuring the dispersions of the poststimular histograms it was found that under the effect of trifluoperazine there occurred a reduction of the value and the duration of the responses of the cortical neurons after the infliction of stimulation. The effect obtained after the administration of trifluoperazine was regarded from the point of view of aggravation of the signal conduction in the neuronal reticula.", "contents": "[Effect of triftazin on the transmission of excitation in the brain of the rabbit under the prolonged administration of the preparation]. Experiments were conducted on awake rabbits to which trifluoperazine was given daily for 2 weeks in a dose of 1 mg/kg a day; a study was made of the reaction of the cortical neurones in response to the electrostimulation of its adjacent areas. In measuring the dispersions of the poststimular histograms it was found that under the effect of trifluoperazine there occurred a reduction of the value and the duration of the responses of the cortical neurons after the infliction of stimulation. The effect obtained after the administration of trifluoperazine was regarded from the point of view of aggravation of the signal conduction in the neuronal reticula."} {"id": "PMID:171015", "title": "[Effect of catecholaminergic substances on the proconvulsive properties of the caudate nucleus].", "content": "In the freely moving rats stimulants of catecholaminergic tramission (DOPA, apomorphine, d,1-amphetamine, and also their combination with disulfiram) reduced the proconvulsive properties of the caudate nucleus. Under the effect of these substances there occurred a shortening of the cortical electroencephalographic response to a single stimulation of the nucleus in the animals given subconvulsive doses of pentaxylenetetrazol and a reduction of the extent of the spike-wave rhythm induced by the repeated caudate stimuli. On the contrary, inhibitors of catecholaminergic transmission (chlorpromazine, haloperidol, alpha-methyltyrosine and disulfiram) intensified the proconvulsive effect of the caudate nucleus.", "contents": "[Effect of catecholaminergic substances on the proconvulsive properties of the caudate nucleus]. In the freely moving rats stimulants of catecholaminergic tramission (DOPA, apomorphine, d,1-amphetamine, and also their combination with disulfiram) reduced the proconvulsive properties of the caudate nucleus. Under the effect of these substances there occurred a shortening of the cortical electroencephalographic response to a single stimulation of the nucleus in the animals given subconvulsive doses of pentaxylenetetrazol and a reduction of the extent of the spike-wave rhythm induced by the repeated caudate stimuli. On the contrary, inhibitors of catecholaminergic transmission (chlorpromazine, haloperidol, alpha-methyltyrosine and disulfiram) intensified the proconvulsive effect of the caudate nucleus."} {"id": "PMID:171016", "title": "[Effect of sodium oxybutyrate on regional blood circulation and on neural regulation of vascular tonus].", "content": "The effect of sodium hydroxybutyrate on the blood flow in the aorta, carotid, mesenteric and femoral arteries were studied on cats and dogs. The circulation was assessed by the electromagnetic and resistographic methods, in the anesthetized and nonanesthetized animals. The tonic activity was recorded in the sympathetic nerves and the EEG. Sodium hydroxybutrate was shown to decrease the sympathetic activity, resulting in the increase of the regional circulation and induced the EEG synchronization. The latter effect was more pronounced in the arotid arteries. It can be assumed that sodium hydroxybutyrate affects the nervous control of the blood vessels.", "contents": "[Effect of sodium oxybutyrate on regional blood circulation and on neural regulation of vascular tonus]. The effect of sodium hydroxybutyrate on the blood flow in the aorta, carotid, mesenteric and femoral arteries were studied on cats and dogs. The circulation was assessed by the electromagnetic and resistographic methods, in the anesthetized and nonanesthetized animals. The tonic activity was recorded in the sympathetic nerves and the EEG. Sodium hydroxybutrate was shown to decrease the sympathetic activity, resulting in the increase of the regional circulation and induced the EEG synchronization. The latter effect was more pronounced in the arotid arteries. It can be assumed that sodium hydroxybutyrate affects the nervous control of the blood vessels."} {"id": "PMID:171017", "title": "An electrophysiological analysis of the effects of reserpine on adrenergic neuromuscular transmission.", "content": "1 An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles less than 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release. 2 Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%. 3 Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone. 4 During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady-state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 5 These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis.", "contents": "An electrophysiological analysis of the effects of reserpine on adrenergic neuromuscular transmission. 1 An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles less than 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release. 2 Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%. 3 Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone. 4 During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady-state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 5 These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis."} {"id": "PMID:171018", "title": "An electrophysiological analysis of the effect of Ca ions on neuromuscular transmission in the mouse vas deferens.", "content": "1 A study has been made of the effects of changing the external calcium concentration [Ca]0 and the external magnesium concentration [Mg]0 on the synaptic potential due to noradrenaline release. 2 When [Ca]0 was varied in the range 0.7 to 1.8 mM, the synaptic potential increased as about the second power of [Ca]0. 3 Increasing [Mg]0 depressed the synaptic potential; however, variation of [Ca]0 in the presence of high [Mg]0 did not significantly change the power relationship between the synaptic potential and [Ca]0. 4 The facilitated increase in the synaptic potential during short trains of impulses at different frequencies was quantitatively predicted on the assumption that each impulse leaves residual Ca ions bound to release receptors in the nerve terminal.", "contents": "An electrophysiological analysis of the effect of Ca ions on neuromuscular transmission in the mouse vas deferens. 1 A study has been made of the effects of changing the external calcium concentration [Ca]0 and the external magnesium concentration [Mg]0 on the synaptic potential due to noradrenaline release. 2 When [Ca]0 was varied in the range 0.7 to 1.8 mM, the synaptic potential increased as about the second power of [Ca]0. 3 Increasing [Mg]0 depressed the synaptic potential; however, variation of [Ca]0 in the presence of high [Mg]0 did not significantly change the power relationship between the synaptic potential and [Ca]0. 4 The facilitated increase in the synaptic potential during short trains of impulses at different frequencies was quantitatively predicted on the assumption that each impulse leaves residual Ca ions bound to release receptors in the nerve terminal."} {"id": "PMID:171021", "title": "Community care: an analysis of assumptions.", "content": "The implementation of a policy of \"community care' is seen to involve a number of assumptions, some of which are rarely examined. These can be roughly categorized as involving the nature of mental illness, the nature of community, the course and treatment of mental illness, the proper scope of psychiatry, the burden on the community and the efficacy of social work. Data bearing on these assumptions are reviewed, and the conclusion is offered that they are far from being uncontentious. It is suggested that the movement toward community care has many of the attributes of a moral enterprise which, unless substantiated by benefits to the patient or his family, may be the latest diversion of the psychiatric conscience from the care and treatment of the chronic mentally ill.", "contents": "Community care: an analysis of assumptions. The implementation of a policy of \"community care' is seen to involve a number of assumptions, some of which are rarely examined. These can be roughly categorized as involving the nature of mental illness, the nature of community, the course and treatment of mental illness, the proper scope of psychiatry, the burden on the community and the efficacy of social work. Data bearing on these assumptions are reviewed, and the conclusion is offered that they are far from being uncontentious. It is suggested that the movement toward community care has many of the attributes of a moral enterprise which, unless substantiated by benefits to the patient or his family, may be the latest diversion of the psychiatric conscience from the care and treatment of the chronic mentally ill."} {"id": "PMID:171023", "title": "Extra-osseous localization of 99Tcm-Sn pyrophosphate.", "content": "99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age.", "contents": "Extra-osseous localization of 99Tcm-Sn pyrophosphate. 99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age."} {"id": "PMID:171024", "title": "The nitrofurans as sperm immobilising agents: their tissue toxicity and their clinical application.", "content": "Nitrofurantoin sodium and nitrofurazone in certain critical concentrations have the ability to cause sperm immobilisation. Intraoperative vas irrigation with these solutions in 24 patients have produced sterility in the immediate postoperative period.", "contents": "The nitrofurans as sperm immobilising agents: their tissue toxicity and their clinical application. Nitrofurantoin sodium and nitrofurazone in certain critical concentrations have the ability to cause sperm immobilisation. Intraoperative vas irrigation with these solutions in 24 patients have produced sterility in the immediate postoperative period."} {"id": "PMID:171025", "title": "The sympathetic nervous system in alcoholic neuropathy. A clinical and pathological study.", "content": "Tests of autonomic function were performed on 12 subjects with alcoholic neuropathy. Abnormal sweat patterns occurred in 8/8 (100 per cent) and an abnormal Valsalva ratio in 2/9 (22 per cent). Postural hypotension and denervation hypersensitivity were absent in all patients examined. A quantitative assessment of baroreceptor function was made. The resting heart period, heart period range and mean gain of alcoholics were within the control range. Quantitative histological studies were performed on the greater splanchnic nerves removed at autopsy in 4 alcoholic subjects. The myelinated fibre density fell within the control range. The absence of significant disturbance of blood pressure control correlates well with the absence of pathology in the greater splanchnic nerve.", "contents": "The sympathetic nervous system in alcoholic neuropathy. A clinical and pathological study. Tests of autonomic function were performed on 12 subjects with alcoholic neuropathy. Abnormal sweat patterns occurred in 8/8 (100 per cent) and an abnormal Valsalva ratio in 2/9 (22 per cent). Postural hypotension and denervation hypersensitivity were absent in all patients examined. A quantitative assessment of baroreceptor function was made. The resting heart period, heart period range and mean gain of alcoholics were within the control range. Quantitative histological studies were performed on the greater splanchnic nerves removed at autopsy in 4 alcoholic subjects. The myelinated fibre density fell within the control range. The absence of significant disturbance of blood pressure control correlates well with the absence of pathology in the greater splanchnic nerve."} {"id": "PMID:171026", "title": "Recurrent brachial plexus neuropathy.", "content": "The clinical, electrophysiological and pathological changes in 3 patients with recurrent attacks of non-traumatic brachial plexus neuropathy have been described. Two had recurrent attacks and a dominant family history of similar attacks, together with evidence of lesser degrees of nerve involvement outside the brachial plexus. In one patient the attacks were moderately painful, while in the other there was little or no pain. Only one showed undue slowing of motor nerve conduction during ischaemia, but in both cases the sural nerves had the changes of tomaculous neuropathy, with many sausage-shaped swellings of the myelin sheaths, and extensive segmental demyelination and remyelination. The third patient had two attacks of acute brachial plexus neuropathy which were both extremely painful. The clinical features were compatible with a diagnosis of neuralgic amuotrophy. In the second attack, there was vagus nerve involvement and the sural nerve showed evidence of healed extensive segmental demyelination. The various syndromes presenting with acute non-traumatic brachial plexus neuropathy are reviewed, and a tentative nonsological classification advanced. Most patients fall into the category of acute, painful paralysis with amyotrophy, with no family history and no evidence of lesions outside the brachial plexus. It is suggested that the term \"neuralgic amyotrophy\" be restricted to this group. Patients with features outside this clinical picture probably suffer from other disease entities presenting with brachial plexus neuropathy. The familial cases constitute one or more aetioliogical subgroups, differing from neuralgic amyotrophy in the frequency of recurrences, the relative freedom from pain in the attacks, the frequency of nerve lesions outside the brachial plexus, and of hypotelorism. Individual attacks of acute brachial plexus neuropathy, however, may be identical in patients with the different diseases, and further pathological and biochemical studies are awaited to aid in nosology.", "contents": "Recurrent brachial plexus neuropathy. The clinical, electrophysiological and pathological changes in 3 patients with recurrent attacks of non-traumatic brachial plexus neuropathy have been described. Two had recurrent attacks and a dominant family history of similar attacks, together with evidence of lesser degrees of nerve involvement outside the brachial plexus. In one patient the attacks were moderately painful, while in the other there was little or no pain. Only one showed undue slowing of motor nerve conduction during ischaemia, but in both cases the sural nerves had the changes of tomaculous neuropathy, with many sausage-shaped swellings of the myelin sheaths, and extensive segmental demyelination and remyelination. The third patient had two attacks of acute brachial plexus neuropathy which were both extremely painful. The clinical features were compatible with a diagnosis of neuralgic amuotrophy. In the second attack, there was vagus nerve involvement and the sural nerve showed evidence of healed extensive segmental demyelination. The various syndromes presenting with acute non-traumatic brachial plexus neuropathy are reviewed, and a tentative nonsological classification advanced. Most patients fall into the category of acute, painful paralysis with amyotrophy, with no family history and no evidence of lesions outside the brachial plexus. It is suggested that the term \"neuralgic amyotrophy\" be restricted to this group. Patients with features outside this clinical picture probably suffer from other disease entities presenting with brachial plexus neuropathy. The familial cases constitute one or more aetioliogical subgroups, differing from neuralgic amyotrophy in the frequency of recurrences, the relative freedom from pain in the attacks, the frequency of nerve lesions outside the brachial plexus, and of hypotelorism. Individual attacks of acute brachial plexus neuropathy, however, may be identical in patients with the different diseases, and further pathological and biochemical studies are awaited to aid in nosology."} {"id": "PMID:171027", "title": "Unmyelinated fibres and Schwann cells of sural nerve in neuropathy.", "content": "Electron micrographs of 45 sural nerves from patients with acquired (22) or heredodegenerative neuropathy (23) were analysed with respect to the number of unmyelinated nerve fibres, 37 nerves with respect to the number of Schwann cell sub-units and of structures connected with Schwann cells. Findings were compared with those in 6 nerves from control subjects and referred to the total number rather than to the number per mm2 to eliminate error due to increase in the transverse endoneurial area, present in more than half the diseased nerves. Ninety-one per cent of the diseased nerves showed one or several abnormalities in unmyelinated fibres of their Schwann cells. The best indicator of fibre loss was an increase in the number of Schwann cell sub-units devoid of axons, found in more than half the nerves. This was the only abnormality related with decrease in number of myelinated fibres. The increase in number of empty Schwann cell sub-units was due both to loss of unmyelinated nerve fibres and to proliferation of Schwann cells. Proliferation was indicated by the higher incidence of Schwann cell nuclei in cross-sections of diseased nerves than in controls. The earliest sign of involvement was an increase in number of profiles and of small isolated Schwann cell projections, observed in 33 of 37 diseased nerves, as the only abnormality in 7 nerves. The number of unmyelinated nerve fibres by itself was of little value to indicate loss of fibres, since regeneration often replaced or more than replaced degenerated fibres. Regeneration was indicated by an increase in number or incidence of small unmyelinated fibres, present in nearly half of 45 diseased nerves; and by an increased in the total number, present in a third of the nerves. An increase in the number of collagen pockets and of fibres undergoing degeneration (loss of organelles) and a decrease in the number of unmyelinated fibres per Schwann cell sub-units was present in only a quarter to a third of diseased nerves and was not related to other criteria of loss of fibres or of regneration.", "contents": "Unmyelinated fibres and Schwann cells of sural nerve in neuropathy. Electron micrographs of 45 sural nerves from patients with acquired (22) or heredodegenerative neuropathy (23) were analysed with respect to the number of unmyelinated nerve fibres, 37 nerves with respect to the number of Schwann cell sub-units and of structures connected with Schwann cells. Findings were compared with those in 6 nerves from control subjects and referred to the total number rather than to the number per mm2 to eliminate error due to increase in the transverse endoneurial area, present in more than half the diseased nerves. Ninety-one per cent of the diseased nerves showed one or several abnormalities in unmyelinated fibres of their Schwann cells. The best indicator of fibre loss was an increase in the number of Schwann cell sub-units devoid of axons, found in more than half the nerves. This was the only abnormality related with decrease in number of myelinated fibres. The increase in number of empty Schwann cell sub-units was due both to loss of unmyelinated nerve fibres and to proliferation of Schwann cells. Proliferation was indicated by the higher incidence of Schwann cell nuclei in cross-sections of diseased nerves than in controls. The earliest sign of involvement was an increase in number of profiles and of small isolated Schwann cell projections, observed in 33 of 37 diseased nerves, as the only abnormality in 7 nerves. The number of unmyelinated nerve fibres by itself was of little value to indicate loss of fibres, since regeneration often replaced or more than replaced degenerated fibres. Regeneration was indicated by an increase in number or incidence of small unmyelinated fibres, present in nearly half of 45 diseased nerves; and by an increased in the total number, present in a third of the nerves. An increase in the number of collagen pockets and of fibres undergoing degeneration (loss of organelles) and a decrease in the number of unmyelinated fibres per Schwann cell sub-units was present in only a quarter to a third of diseased nerves and was not related to other criteria of loss of fibres or of regneration."} {"id": "PMID:171028", "title": "Effects of activity in non-myelinated afferent fibres on the spinocervical tract.", "content": "Microelectrode recordings were made from axons of the spinocervical tract (SCT) in unanaesthetized decerebrate-spinal cats. Pure volleys in non-myelinated (C) cutaneous nerve fibres were obtained by DC-polarization block of conduction in the myelinated (A) fibres, and SCT cells were classified according to whether or not they were excited by C fibres. The effects of conditioning C responses in the SCT with A and C fibre input were examined, as were the effects of conditioning A fibre responses in the tract with C fibre inputs. The effects of stimulating descending systems in the cervical spinal cord on the C fibre-evoked responses of SCT cells were determined. SCT units with a slowly-adapting pressure-sensitive component in their receptive fields responded to cutaneous C fibres in addition to A fibres. Units which responded only to hair movement when the receptive field was stimulated mechanically were not excited by C fibres. Responses in SCT neurones produced by C fibres were profoundly inhibited by conditioning volleys in A fibres of both ipsilateral and contralateral cutaneous nerves and by activity in several descending systems. Conditioning with C fibres failed to affect the responses of SCT cells to either A or C fibres. It is concluded that cutaneous C fibres excite some SCT cells but have no other effect on transmission through this system. It is suggested that there are common inhibitory interneurones in the paths from descending systems and cutaneous A and C fibres to the excitatory input to SCT cells.", "contents": "Effects of activity in non-myelinated afferent fibres on the spinocervical tract. Microelectrode recordings were made from axons of the spinocervical tract (SCT) in unanaesthetized decerebrate-spinal cats. Pure volleys in non-myelinated (C) cutaneous nerve fibres were obtained by DC-polarization block of conduction in the myelinated (A) fibres, and SCT cells were classified according to whether or not they were excited by C fibres. The effects of conditioning C responses in the SCT with A and C fibre input were examined, as were the effects of conditioning A fibre responses in the tract with C fibre inputs. The effects of stimulating descending systems in the cervical spinal cord on the C fibre-evoked responses of SCT cells were determined. SCT units with a slowly-adapting pressure-sensitive component in their receptive fields responded to cutaneous C fibres in addition to A fibres. Units which responded only to hair movement when the receptive field was stimulated mechanically were not excited by C fibres. Responses in SCT neurones produced by C fibres were profoundly inhibited by conditioning volleys in A fibres of both ipsilateral and contralateral cutaneous nerves and by activity in several descending systems. Conditioning with C fibres failed to affect the responses of SCT cells to either A or C fibres. It is concluded that cutaneous C fibres excite some SCT cells but have no other effect on transmission through this system. It is suggested that there are common inhibitory interneurones in the paths from descending systems and cutaneous A and C fibres to the excitatory input to SCT cells."} {"id": "PMID:171029", "title": "Depressive effects of morphine upon lamina V cells activities in the dorsal horn of the spinal cat.", "content": "The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in spinal cats by studying its effects on the activities of lamina V dorsal horn interneurons. Morphine (2 mg/kg i.v.) induced a direct depressive action at the spinal level, since it strongly reduced both spontaneous and evoked activities of lamina V cells. The spontaneous firing rate and the responses elicited by natural nociceptive stimulation were decreased by 50%. The responses of these units evoked by supramaximal electrical stimulation were reduced to 67% of their initial value; in this case, the depressive effect was much more prominent on the late component of the long duration responses. The observed depressive effects are specific since they are immediately reversed by administration of opiate antagonists (nalorphine or naloxone).", "contents": "Depressive effects of morphine upon lamina V cells activities in the dorsal horn of the spinal cat. The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in spinal cats by studying its effects on the activities of lamina V dorsal horn interneurons. Morphine (2 mg/kg i.v.) induced a direct depressive action at the spinal level, since it strongly reduced both spontaneous and evoked activities of lamina V cells. The spontaneous firing rate and the responses elicited by natural nociceptive stimulation were decreased by 50%. The responses of these units evoked by supramaximal electrical stimulation were reduced to 67% of their initial value; in this case, the depressive effect was much more prominent on the late component of the long duration responses. The observed depressive effects are specific since they are immediately reversed by administration of opiate antagonists (nalorphine or naloxone)."} {"id": "PMID:171033", "title": "Intracellular postsynaptic potentials of cat lateral geniculate cells and the effects of degeneration of the optic terminals.", "content": "(1) The synaptic signal transmission was studied in the lateral geniculate nucleus (LGN) during the late phase of degeneration, 50-80 h after light coagulation of the optic disc and the retinal vessels of one eye. Postsynaptic potentials and action potentials were intracellularly recorded from normal LGN principal cells (N-cells) and cells with degenerating optic terminals (D-cells). EPSPs and postsynaptic action potentials were elicited by electrical stimulation of the optic tract. Two neuronal classes (I and II) were characterized according to their response latency to optic tract stimuli. (2) Spontaneous small EPSPs and slow changes of the membrane potential were found in D-cells and the EPSP-IPSP pattern normally present in N-cells was absent. (3) The responses to optic tract stimuli applied at low stimulus frequencies (less than 5 stimuli/sec) were identical in D-cells and N-cells. (4) At higher stimulus frequencies (greater than 50 stimuli/sec), the EPSP amplitude was, on average, significantly smaller in D-cells than in N-cells. (5) At frequencies above 50 stimuli/sec, the fluctuation of the EPSP amplitudes and the latency scattering of postsynaptic action potentials were larger in D-cells than in N-cells. (6) The slope of the rising phase of the EPSPs increased slightly in N-cells and decreased in D-cells when the stimulus frequency was raised from 5/sec to 100/sec (class I cells). (7) The decay time constant of the EPSP, the latency of the onset and the peak amplitude of EPSPs did not change during degeneration. (8) The hypothesis put forward to account for the results is that the amount of transmitter released by each action potential in degenerating terminals is reduced, but its variability is increased. This is probably caused by a reduction in both the transmitter reserve and the transmitter resynthesis, and also by a larger fluctuation of the size of transmitter quanta.", "contents": "Intracellular postsynaptic potentials of cat lateral geniculate cells and the effects of degeneration of the optic terminals. (1) The synaptic signal transmission was studied in the lateral geniculate nucleus (LGN) during the late phase of degeneration, 50-80 h after light coagulation of the optic disc and the retinal vessels of one eye. Postsynaptic potentials and action potentials were intracellularly recorded from normal LGN principal cells (N-cells) and cells with degenerating optic terminals (D-cells). EPSPs and postsynaptic action potentials were elicited by electrical stimulation of the optic tract. Two neuronal classes (I and II) were characterized according to their response latency to optic tract stimuli. (2) Spontaneous small EPSPs and slow changes of the membrane potential were found in D-cells and the EPSP-IPSP pattern normally present in N-cells was absent. (3) The responses to optic tract stimuli applied at low stimulus frequencies (less than 5 stimuli/sec) were identical in D-cells and N-cells. (4) At higher stimulus frequencies (greater than 50 stimuli/sec), the EPSP amplitude was, on average, significantly smaller in D-cells than in N-cells. (5) At frequencies above 50 stimuli/sec, the fluctuation of the EPSP amplitudes and the latency scattering of postsynaptic action potentials were larger in D-cells than in N-cells. (6) The slope of the rising phase of the EPSPs increased slightly in N-cells and decreased in D-cells when the stimulus frequency was raised from 5/sec to 100/sec (class I cells). (7) The decay time constant of the EPSP, the latency of the onset and the peak amplitude of EPSPs did not change during degeneration. (8) The hypothesis put forward to account for the results is that the amount of transmitter released by each action potential in degenerating terminals is reduced, but its variability is increased. This is probably caused by a reduction in both the transmitter reserve and the transmitter resynthesis, and also by a larger fluctuation of the size of transmitter quanta."} {"id": "PMID:171034", "title": "[Role of ACTH in regulation of aldosterone secretion].", "content": "During the nycthemeral cycle, ACTH modulated the aldosterone production and increases plasmatic level at the end of night. The chronic stimulant effect of angiotensin II is a permissive factor of ACTH influence on aldosterone formation.", "contents": "[Role of ACTH in regulation of aldosterone secretion]. During the nycthemeral cycle, ACTH modulated the aldosterone production and increases plasmatic level at the end of night. The chronic stimulant effect of angiotensin II is a permissive factor of ACTH influence on aldosterone formation."} {"id": "PMID:171035", "title": "[Specific insulin binding to chloroplasts isolated from Acetabularia mediterranea].", "content": "Kinetics of insulin fixation to chloroplasts, exponential dissociation of bound hormone, competition between radioactive and native insulins for binding and for release indicate that chloroplasts possess insulin receptors.", "contents": "[Specific insulin binding to chloroplasts isolated from Acetabularia mediterranea]. Kinetics of insulin fixation to chloroplasts, exponential dissociation of bound hormone, competition between radioactive and native insulins for binding and for release indicate that chloroplasts possess insulin receptors."} {"id": "PMID:171036", "title": "[Influence of darkness on insulin binding in the unicellular algae Acetabularia mediterranea].", "content": "Culture of Acetabularia in darkness increases the number of membrane receptor sites to insulin. This increase has not been observed with anucleated parts of algae. It may be concluded that induction of insulin receptor sites depends on the presence of the cell nucleus.", "contents": "[Influence of darkness on insulin binding in the unicellular algae Acetabularia mediterranea]. Culture of Acetabularia in darkness increases the number of membrane receptor sites to insulin. This increase has not been observed with anucleated parts of algae. It may be concluded that induction of insulin receptor sites depends on the presence of the cell nucleus."} {"id": "PMID:171037", "title": "[Spike activity recorded at the level of optic tract in a primate, Papio papio].", "content": "Spike activity has been recorded, in two young baboons, at the part of the optic tract (O.T.) localized between the chiasma and the lateral geniculate (L.G.) during REM and also slow wave sleep, preceding or not a REM period. These spikes, mono or biphasic, were of 60-200 ms duration and of 30-140 muV amplitude. They occurred generally in bursts (up to 50 spikes); 4 to 10 spikes bursts were the more frequent. These O.T. spikes were assimilated to the L.G. spikes.", "contents": "[Spike activity recorded at the level of optic tract in a primate, Papio papio]. Spike activity has been recorded, in two young baboons, at the part of the optic tract (O.T.) localized between the chiasma and the lateral geniculate (L.G.) during REM and also slow wave sleep, preceding or not a REM period. These spikes, mono or biphasic, were of 60-200 ms duration and of 30-140 muV amplitude. They occurred generally in bursts (up to 50 spikes); 4 to 10 spikes bursts were the more frequent. These O.T. spikes were assimilated to the L.G. spikes."} {"id": "PMID:171038", "title": "[Cytoimmunological and histochemical study of cat adenohypophyseal cells, made fluorescent by the Falck and Hillarp technic].", "content": "In the Cat, after Falck and Hillarp method, all the fluorescent cells of the PI and the anterior lobe of adenohypophysis can be revealed with specific anti-sera to ACTH(1-24), ACTH(17-39), bovine beta-MSH and porcine beta-LPH. With the lead hematoxyline staining method, two types of cells are recognizable in the anterior lobe, in which the non hormonal constituents of the granules must be different.", "contents": "[Cytoimmunological and histochemical study of cat adenohypophyseal cells, made fluorescent by the Falck and Hillarp technic]. In the Cat, after Falck and Hillarp method, all the fluorescent cells of the PI and the anterior lobe of adenohypophysis can be revealed with specific anti-sera to ACTH(1-24), ACTH(17-39), bovine beta-MSH and porcine beta-LPH. With the lead hematoxyline staining method, two types of cells are recognizable in the anterior lobe, in which the non hormonal constituents of the granules must be different."} {"id": "PMID:171039", "title": "[Mouse pancreas involvement in murine hepatitis virus infection].", "content": "After intraperitoneal inoculation with mouse hepatitis virus (MHv) into mice, the excretory cells of the pancreas showed a marked vacuolar degeneration concomitantly with hepatitis. MHV-specific antigen was evidenced in the cytoplasm of infected cells. Electron microscopy revealed a number of virions within the matrix, spaces of the endoplasmic reticulum and areas of focal cytoplasmic necrosis. The virus titer of the pancreas was equal or superior to that of the liver at least in early stage of infection.", "contents": "[Mouse pancreas involvement in murine hepatitis virus infection]. After intraperitoneal inoculation with mouse hepatitis virus (MHv) into mice, the excretory cells of the pancreas showed a marked vacuolar degeneration concomitantly with hepatitis. MHV-specific antigen was evidenced in the cytoplasm of infected cells. Electron microscopy revealed a number of virions within the matrix, spaces of the endoplasmic reticulum and areas of focal cytoplasmic necrosis. The virus titer of the pancreas was equal or superior to that of the liver at least in early stage of infection."} {"id": "PMID:171040", "title": "Filaments and granules in mitochondrial vacuoles in chondrocytes.", "content": "As chondrocytes degenerate mitochondria frequently become vacuolated. Vacuoles seem to form by an invagination of mitochondria into their own matrix followed by cytoplasmic invasion. The bounding membrane of vacuoles and the electron dense granules which are intermittently dispersed around its periphery are positive when stained with phosphotungstic acid and with silver nitrate methenamine after periodic acid oxidation, indicating the presence of glycoprotein; they are also positive after staining with colloidal iron and bismuth nitrate, indicating the presence of acid proteoglycans. Within vacuoles and apparently arising from their glycoprotein proteoglycan boundary are small filaments composed of granular and filamentous protions. Vacuoles and their contents are exocytosed thus accounting for the presence of granules and filaments in pericellular lacunae. In pericellular lacunae and in the extracellular matrix, filaments interconnect with granules or with collagen fibrils, or both. Filaments decrease in number as the distance from the cell increases, while granules decrease in size but remain numerous. Filaments and granules decrease in the extracellular matrix as collagen fibrils aggregate and as the matric calcifies. Thus, they may play a role in aggregation of collagen fibrils. Filaments and granules also decrease with increasing age. Filaments and granules do not seem to be derived from Golgi vacuoles. They are present in costal, tracheal, and epiphyseal cartilage in three different species of animals.", "contents": "Filaments and granules in mitochondrial vacuoles in chondrocytes. As chondrocytes degenerate mitochondria frequently become vacuolated. Vacuoles seem to form by an invagination of mitochondria into their own matrix followed by cytoplasmic invasion. The bounding membrane of vacuoles and the electron dense granules which are intermittently dispersed around its periphery are positive when stained with phosphotungstic acid and with silver nitrate methenamine after periodic acid oxidation, indicating the presence of glycoprotein; they are also positive after staining with colloidal iron and bismuth nitrate, indicating the presence of acid proteoglycans. Within vacuoles and apparently arising from their glycoprotein proteoglycan boundary are small filaments composed of granular and filamentous protions. Vacuoles and their contents are exocytosed thus accounting for the presence of granules and filaments in pericellular lacunae. In pericellular lacunae and in the extracellular matrix, filaments interconnect with granules or with collagen fibrils, or both. Filaments decrease in number as the distance from the cell increases, while granules decrease in size but remain numerous. Filaments and granules decrease in the extracellular matrix as collagen fibrils aggregate and as the matric calcifies. Thus, they may play a role in aggregation of collagen fibrils. Filaments and granules also decrease with increasing age. Filaments and granules do not seem to be derived from Golgi vacuoles. They are present in costal, tracheal, and epiphyseal cartilage in three different species of animals."} {"id": "PMID:171041", "title": "An electron microscopic study on the formation of the periostracum in Helisoma (Mollusca).", "content": "The ultrastructure of the cells involved in the formation of the periostracum in Helisoma duryi duryi is described. Two distinct types of periostracal cells can be recognized: light and dark. The Golgi complexes of the light cell are involved in the biogenesis of periostracal units which are extruded at the base of the periostracal groove. Here they align into a single row so as to form the membrane-like lamellar covering of the periostracum. While the secretions of the dark periostracal cells contribute to the initial component of the dark layer of the periostracum, the mantle edge gland cells are responsible for its thickening. The adult periostracum is about 2--3 mum thick and it consists of a single dark layer covered by a membrane-like lamellar structure.", "contents": "An electron microscopic study on the formation of the periostracum in Helisoma (Mollusca). The ultrastructure of the cells involved in the formation of the periostracum in Helisoma duryi duryi is described. Two distinct types of periostracal cells can be recognized: light and dark. The Golgi complexes of the light cell are involved in the biogenesis of periostracal units which are extruded at the base of the periostracal groove. Here they align into a single row so as to form the membrane-like lamellar covering of the periostracum. While the secretions of the dark periostracal cells contribute to the initial component of the dark layer of the periostracum, the mantle edge gland cells are responsible for its thickening. The adult periostracum is about 2--3 mum thick and it consists of a single dark layer covered by a membrane-like lamellar structure."} {"id": "PMID:171042", "title": "Comparison of the effect of various methods of dissociation on the protein composition of rat liver ribosomal subunits.", "content": "Rat liver ribosomes were dissociated into subunits using EDTA, sodium pyrophosphate, high concentrations of KC1, as well as by incubation with puromycin in presence of 0.5 M KC1. The subunits obtained were analyzed using the density gradient centrifugation technique and their ribosomal proteins were separated by means of two-dimensional polyacrylamide gel electrophoresis. The ribosomal protein patterns of the two subunits isolated using each of the dissociating method were compared to the protein patterns of monosomes prepared by puromycin treatment alone. Our results revealed that the use of chelating agents to dissociate the ribosomes resulted in the loss of some ribosomal proteins from the small subunit. On the other hand, the use of KC1 in high concentrations to dissociate the ribosomes did not appear to cause any major loss of proteins from the ribosomes except for some acidic proteins.", "contents": "Comparison of the effect of various methods of dissociation on the protein composition of rat liver ribosomal subunits. Rat liver ribosomes were dissociated into subunits using EDTA, sodium pyrophosphate, high concentrations of KC1, as well as by incubation with puromycin in presence of 0.5 M KC1. The subunits obtained were analyzed using the density gradient centrifugation technique and their ribosomal proteins were separated by means of two-dimensional polyacrylamide gel electrophoresis. The ribosomal protein patterns of the two subunits isolated using each of the dissociating method were compared to the protein patterns of monosomes prepared by puromycin treatment alone. Our results revealed that the use of chelating agents to dissociate the ribosomes resulted in the loss of some ribosomal proteins from the small subunit. On the other hand, the use of KC1 in high concentrations to dissociate the ribosomes did not appear to cause any major loss of proteins from the ribosomes except for some acidic proteins."} {"id": "PMID:171043", "title": "Inhibition of phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells infected with Semliki Forest virus.", "content": "Semliki Forest virus inhibits phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells 6 h after infection. Viral infection reduced the incorporation of [1,2-14C]-ethanolamine into intact cells by approximately 50%. A similar reduction in the activity of the ethanolaminephosphotransferase (EC 2.7.8.1) was also observed. The apparent Km for CDPethanolamine was 60 muM for the microsomal enzymes from infected or mock-infected cells. In addition, exogenous diglyceride only stimulated by 1.5-fold the ethanolaminephosphotransferase from virus- or mock-infected cells, whereas the same diglyceride preparations stimulated the cholinephosphotransferase (EC 2.7.8.2) from baby hamster kidney cells by sixfold. Generation of endogenous diglyceride by pretreatment of the microsomes with phospholipase C (EC 3.1.4.3) stimulated the activity of the cholinephosphotransferase but not the ethanolaminephosphotranferase. Semliki Forest virus does not inhibit all microsomal enzymes, since the activities of NADH- K3Fe(CN)6 reductase and NADH dehydrogenase (EC 1.6.99.3) were not affected. The ethanolaminephosphotransferase from virus- and mock-infected cells showed similar profiles of activity as a function of temperature; this result and other studies suggest that that membranous environment of the ethanolaminephosphotransferase was not significantly modified by the virus.", "contents": "Inhibition of phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells infected with Semliki Forest virus. Semliki Forest virus inhibits phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells 6 h after infection. Viral infection reduced the incorporation of [1,2-14C]-ethanolamine into intact cells by approximately 50%. A similar reduction in the activity of the ethanolaminephosphotransferase (EC 2.7.8.1) was also observed. The apparent Km for CDPethanolamine was 60 muM for the microsomal enzymes from infected or mock-infected cells. In addition, exogenous diglyceride only stimulated by 1.5-fold the ethanolaminephosphotransferase from virus- or mock-infected cells, whereas the same diglyceride preparations stimulated the cholinephosphotransferase (EC 2.7.8.2) from baby hamster kidney cells by sixfold. Generation of endogenous diglyceride by pretreatment of the microsomes with phospholipase C (EC 3.1.4.3) stimulated the activity of the cholinephosphotransferase but not the ethanolaminephosphotranferase. Semliki Forest virus does not inhibit all microsomal enzymes, since the activities of NADH- K3Fe(CN)6 reductase and NADH dehydrogenase (EC 1.6.99.3) were not affected. The ethanolaminephosphotransferase from virus- and mock-infected cells showed similar profiles of activity as a function of temperature; this result and other studies suggest that that membranous environment of the ethanolaminephosphotransferase was not significantly modified by the virus."} {"id": "PMID:171044", "title": "Chemodectoma of the larynx.", "content": "The ninettenth reported case of chemodectoma of the larynx is presented and its management discussed. Some reflections on the laryngeal paraganglia are made and the past literature is reviewed.", "contents": "Chemodectoma of the larynx. The ninettenth reported case of chemodectoma of the larynx is presented and its management discussed. Some reflections on the laryngeal paraganglia are made and the past literature is reviewed."} {"id": "PMID:171045", "title": "Chemodectomas of the head and neck.", "content": "Chemodectomas of the head and neck are reviewed. Their clinical picture, frequent multicentric origin, microscopie and macroscopic picture are discussed as well as their roentgenologic appearance. The role of angiography in their diagnosis is emphasized.", "contents": "Chemodectomas of the head and neck. Chemodectomas of the head and neck are reviewed. Their clinical picture, frequent multicentric origin, microscopie and macroscopic picture are discussed as well as their roentgenologic appearance. The role of angiography in their diagnosis is emphasized."} {"id": "PMID:171046", "title": "Infectious pancreatic necrosis (IPN) virus carriers and antibody production in a population of rainbow trout (Salmo gairdneri).", "content": "A total of three hundred and fifty-seven 2-year-old rainbow trout from a hatchery were examined for IPN virus over a period of 5 months. The overall virus isolation rate was 23.2%. The kidneys yielded virus most frequently while the spleen and pancreas-caeca yielded virus less frequently, and the gonads and feces yielded virus infrequently. During this period there was a decline in carrier rate as well as a decline in the numbers of infectious virions in the organs. These decreases were accompanied by elevated levels of neutralizing antibody in the sera. Fish with higher antibody levels were found to lose their IPN carrier status more frequently than those with lower antibody levels.", "contents": "Infectious pancreatic necrosis (IPN) virus carriers and antibody production in a population of rainbow trout (Salmo gairdneri). A total of three hundred and fifty-seven 2-year-old rainbow trout from a hatchery were examined for IPN virus over a period of 5 months. The overall virus isolation rate was 23.2%. The kidneys yielded virus most frequently while the spleen and pancreas-caeca yielded virus less frequently, and the gonads and feces yielded virus infrequently. During this period there was a decline in carrier rate as well as a decline in the numbers of infectious virions in the organs. These decreases were accompanied by elevated levels of neutralizing antibody in the sera. Fish with higher antibody levels were found to lose their IPN carrier status more frequently than those with lower antibody levels."} {"id": "PMID:171047", "title": "Cytoplasmic inclusions in canine cells infected with infectious canine laryngotracheitis (ICL) adenovirus.", "content": "Spherical dark inclusions were observed in both the cytoplasm and nuclei of infectious canine laryngotracheitis (ICL) adenovirus infected MDCK (Madin-Darby Canine Kidney) cells. The distribution of these inclusions in the cells appeared to indicate that they were formed in both the cytoplasm and in the nucleus at about the same time and there did not appear to be movement of these inclusions between the cytoplasm and the nucleus during the early stages of infection. Morphological appearance, 3H-leucine autoradiography, and immunoferritin labelling showed that the cytoplasmic inclusions were similar in nature to the dark nuclear inclusions, and contained the adenovirus hexon antigen, but not the penton base and fiber antigens.", "contents": "Cytoplasmic inclusions in canine cells infected with infectious canine laryngotracheitis (ICL) adenovirus. Spherical dark inclusions were observed in both the cytoplasm and nuclei of infectious canine laryngotracheitis (ICL) adenovirus infected MDCK (Madin-Darby Canine Kidney) cells. The distribution of these inclusions in the cells appeared to indicate that they were formed in both the cytoplasm and in the nucleus at about the same time and there did not appear to be movement of these inclusions between the cytoplasm and the nucleus during the early stages of infection. Morphological appearance, 3H-leucine autoradiography, and immunoferritin labelling showed that the cytoplasmic inclusions were similar in nature to the dark nuclear inclusions, and contained the adenovirus hexon antigen, but not the penton base and fiber antigens."} {"id": "PMID:171048", "title": "Multiple neoplasms in two siblings with a variant form of Fanconi's anemia.", "content": "Two siblings with a variant form of Fanconi's anemia developed multiple neoplasms after prolonged survival and treatment with androgens. One of the siblings developed two separate oral squamous cell carcinomata, and the other developed acute leukemia and hepatoma. Androgens may have had a carcinogenic role in the appearance of the hepatic neoplasm. There is an increased incidence of neoplasm associated with Fanconi's anemia. This may be related to frequent spontaneous chromosomal abberations and/or to increased cellular susceptibility to viral transformation.", "contents": "Multiple neoplasms in two siblings with a variant form of Fanconi's anemia. Two siblings with a variant form of Fanconi's anemia developed multiple neoplasms after prolonged survival and treatment with androgens. One of the siblings developed two separate oral squamous cell carcinomata, and the other developed acute leukemia and hepatoma. Androgens may have had a carcinogenic role in the appearance of the hepatic neoplasm. There is an increased incidence of neoplasm associated with Fanconi's anemia. This may be related to frequent spontaneous chromosomal abberations and/or to increased cellular susceptibility to viral transformation."} {"id": "PMID:171049", "title": "Small cell epidermoid carcinoma of the esophagus. An oat-cell-like carcinoma.", "content": "A case of small cell anaplastic epidermoid carcinoma of the esophagus is reported. The morphology of this rare esophageal neoplasm simulates that of oat cell carcinoma. Four similar cases have been previously reported. The finding of epidermoid differentiation in two of these tumors, including the present one, raises considerable doubt that any are truly oat cell carcinomas of the esophagus. Although it is theoretically possible that an oat cell carcinoma may arise in the esophagus, there is as yet no conclusive evidence for the existence of such an entity.", "contents": "Small cell epidermoid carcinoma of the esophagus. An oat-cell-like carcinoma. A case of small cell anaplastic epidermoid carcinoma of the esophagus is reported. The morphology of this rare esophageal neoplasm simulates that of oat cell carcinoma. Four similar cases have been previously reported. The finding of epidermoid differentiation in two of these tumors, including the present one, raises considerable doubt that any are truly oat cell carcinomas of the esophagus. Although it is theoretically possible that an oat cell carcinoma may arise in the esophagus, there is as yet no conclusive evidence for the existence of such an entity."} {"id": "PMID:171050", "title": "Hypercalcemia in small cell (oat cell) carcinoma of the lung. Coincident parathyroid adenoma in one case.", "content": "Hypercalcemia is very uncommon in small cell (oat cell) carcinoma of the lung. Two cases of this neoplasm associated with symptomatic hypercalcemia are described. Despite normal skeletal roentgenograms, metastatic bone disease was demonstrated by abnormal bone scans and bone biopsies in both patients. The combination of conventional antihypercalcemia therapy, cytotoxic cancer chemotherapy, and synthetic salmon calcitonin corrected the hypercalcemia despite progression of the small cell carcinoma. One patient with elevated serum immunoreactive parathyroid hormone (PTH) had a parathyroid adenoma at autopsy. This association emphasizes that in cases of bronchogenic small cell carcinoma with hypercalcemia, conincidental primary hyperparathyroidism should be considered.", "contents": "Hypercalcemia in small cell (oat cell) carcinoma of the lung. Coincident parathyroid adenoma in one case. Hypercalcemia is very uncommon in small cell (oat cell) carcinoma of the lung. Two cases of this neoplasm associated with symptomatic hypercalcemia are described. Despite normal skeletal roentgenograms, metastatic bone disease was demonstrated by abnormal bone scans and bone biopsies in both patients. The combination of conventional antihypercalcemia therapy, cytotoxic cancer chemotherapy, and synthetic salmon calcitonin corrected the hypercalcemia despite progression of the small cell carcinoma. One patient with elevated serum immunoreactive parathyroid hormone (PTH) had a parathyroid adenoma at autopsy. This association emphasizes that in cases of bronchogenic small cell carcinoma with hypercalcemia, conincidental primary hyperparathyroidism should be considered."} {"id": "PMID:171051", "title": "Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma. A case report.", "content": "A case of extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma is presented. Extramammary Paget's disease is not uncommonly seen in regions where apocrine glands are prevalent, with or without underlying apocrine gland carcinoma. This is the first case, to our knowledge, of this association in the external ear canal.", "contents": "Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma. A case report. A case of extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma is presented. Extramammary Paget's disease is not uncommonly seen in regions where apocrine glands are prevalent, with or without underlying apocrine gland carcinoma. This is the first case, to our knowledge, of this association in the external ear canal."} {"id": "PMID:171052", "title": "Mucinous adenocarcinomas of nose and paranasal sinuses.", "content": "This study concerns the Clinicopathologic findings for 18 patients with mucinous adenocarcinomas of nose and/or paranasal sinuses. Males in the 5th decade of life predominated in the series. Nasal obstruction, a growing mass in a sinus, or epistaxis were the most frequent complaints. Ten patients had tumors in the maxillary antrum, and the nasal cavity was the site in 5 patients. Histopathologically, the tumors were moderately to well differentiated, with a few poorly differentiated types. Tumor with the solid pattern of growth were anaplastic; these patients had poorer prognoses. For most patients, treatment consisted of radical surgery alone or in combination with radiotherapy. Of 13 patients for whom survival could be adequately evaluated, 7 died from the tumors, 5 are alive and free of disease more than 4 years, and 1 is living with recurrent tumor 14 months after diagnosis.", "contents": "Mucinous adenocarcinomas of nose and paranasal sinuses. This study concerns the Clinicopathologic findings for 18 patients with mucinous adenocarcinomas of nose and/or paranasal sinuses. Males in the 5th decade of life predominated in the series. Nasal obstruction, a growing mass in a sinus, or epistaxis were the most frequent complaints. Ten patients had tumors in the maxillary antrum, and the nasal cavity was the site in 5 patients. Histopathologically, the tumors were moderately to well differentiated, with a few poorly differentiated types. Tumor with the solid pattern of growth were anaplastic; these patients had poorer prognoses. For most patients, treatment consisted of radical surgery alone or in combination with radiotherapy. Of 13 patients for whom survival could be adequately evaluated, 7 died from the tumors, 5 are alive and free of disease more than 4 years, and 1 is living with recurrent tumor 14 months after diagnosis."} {"id": "PMID:171053", "title": "Wilms' tumor--histologic variation and prognosis.", "content": "A histologic analysis of 75 consecutive cases of Wilms' tumor in the Manchester (England) hospital region has been carried out. A classification based on the tubular status is described. A comparison of the histologic findings with the clinical staging and survival was undertaken, and it was found that the histologic classification was significantly correlated with both stage and survival.", "contents": "Wilms' tumor--histologic variation and prognosis. A histologic analysis of 75 consecutive cases of Wilms' tumor in the Manchester (England) hospital region has been carried out. A classification based on the tubular status is described. A comparison of the histologic findings with the clinical staging and survival was undertaken, and it was found that the histologic classification was significantly correlated with both stage and survival."} {"id": "PMID:171054", "title": "The value of isolation procedures for cytomegalovirus infections in children with leukemia.", "content": "Standard contagious isolation procedures were used for 83 patients with acute lymphocytic leukemia and serologic and/or cultural evidence of cytomegalovirus infection. The infection rate, as determined serologically, for 9 months before and 13 months during isolation procedures was not decreased. Since the techniques employed were not helpful in preventing infection with cytomegalovirus in the immunosuppressed host, they have been discontinued at this hospital.", "contents": "The value of isolation procedures for cytomegalovirus infections in children with leukemia. Standard contagious isolation procedures were used for 83 patients with acute lymphocytic leukemia and serologic and/or cultural evidence of cytomegalovirus infection. The infection rate, as determined serologically, for 9 months before and 13 months during isolation procedures was not decreased. Since the techniques employed were not helpful in preventing infection with cytomegalovirus in the immunosuppressed host, they have been discontinued at this hospital."} {"id": "PMID:171055", "title": "Actinomycin D as the primary agent for gestational trophoblastic disease.", "content": "Thirty-one patients with nonmetastatic trophoblastic disease (NMTD) and 39 patients with metastatic trophoblastic disease (MTD) of gestational origin were treated primarily with actinomycin D. Complete and sustained remission was achieved with actinomycin D alone in 94% of patients with NMTD and 67% with MTD. In the nonmetastatic group, 93% of patients without choriocarcinoma (non-CCA) achieved remission with actinomycin D, as compared to 100% (only 3 patients) with CCA. in the metastatic group, 76% of patients without CCA achieved remission with actinomycin D, as compared to 56% where CCA was present. Fourteen of the 15 patients who failed to respond completely to actinomycin D alone subsequently responded to methotrexate (10 patients), triple therapy (3 patients), methotrexate plus triple therapy (1 patient), and methotrexate plus vinblastine (1 patient). One patient died with widespread metastases despite intensive chemotherapy with actinomycin D and triple therapy. No serious toxic side effects were encountered even in treated patients with pre-existing laboratory evidence of impaired hepatic function.", "contents": "Actinomycin D as the primary agent for gestational trophoblastic disease. Thirty-one patients with nonmetastatic trophoblastic disease (NMTD) and 39 patients with metastatic trophoblastic disease (MTD) of gestational origin were treated primarily with actinomycin D. Complete and sustained remission was achieved with actinomycin D alone in 94% of patients with NMTD and 67% with MTD. In the nonmetastatic group, 93% of patients without choriocarcinoma (non-CCA) achieved remission with actinomycin D, as compared to 100% (only 3 patients) with CCA. in the metastatic group, 76% of patients without CCA achieved remission with actinomycin D, as compared to 56% where CCA was present. Fourteen of the 15 patients who failed to respond completely to actinomycin D alone subsequently responded to methotrexate (10 patients), triple therapy (3 patients), methotrexate plus triple therapy (1 patient), and methotrexate plus vinblastine (1 patient). One patient died with widespread metastases despite intensive chemotherapy with actinomycin D and triple therapy. No serious toxic side effects were encountered even in treated patients with pre-existing laboratory evidence of impaired hepatic function."} {"id": "PMID:171056", "title": "Combination chemotherapy in oat cell carcinoma of the lung.", "content": "Twenty-eight patients with oat cell carcinoma of the lung were treated with cyclophosphamide, vincristine, procarbazine, and prednisone with and without irradiation. Median survival was significantly increased in this treatment group (10 months) as compared to a retrospective radiation alone series (5 months). Intensive chemotherapy with this four-drug regimen represents an initial step in effective management of this disorder.", "contents": "Combination chemotherapy in oat cell carcinoma of the lung. Twenty-eight patients with oat cell carcinoma of the lung were treated with cyclophosphamide, vincristine, procarbazine, and prednisone with and without irradiation. Median survival was significantly increased in this treatment group (10 months) as compared to a retrospective radiation alone series (5 months). Intensive chemotherapy with this four-drug regimen represents an initial step in effective management of this disorder."} {"id": "PMID:171057", "title": "Preoperative irradiation of cancer of the lung: final report of a therapeutic trial. A collaborative study.", "content": "Between May, 1963 and December, 1966, 17 medical centers cooperated in two separate but integrated therapeutic trials of primary lung cancer. One study was of patients with lesions considered operable at the time of diagnosis, and the other of patients with initially inoperable cancer but who were considered potentially operable after radiotherapy. Patients operable at the time of diagnosis were randomly assigned to receive either immediate surgery (278 patients) or preoperative radiotherapy followed by surgery (290 patients). All but one were followed until death or 5 years survival. Survival to each anniversary after randomization was almost identical for the two groups. At 5 years the survival rate was 14% after preoperative radiotherapy and 16% after immediate surgery. On the basis of the small standard error of the difference between these survival rates, a large advantage or a large disadvantage for preoperative radiotherapy is unlikely. Recurrence of cancer either locally or as distant metastasis was also similar in the two groups. Postoperative mortality was estimated to be 11% in the immediate surgery group, but cannot be estimated in a comparable fashion for the irradiated group. Certain postoperative complications were more frequent in the irradiated group, but survival during the first was not affected. Out of 425 patients initially considered to be inoperable, 152 were considered resectable after radiotherapy. These patients were randomly assigned to have either a thoracotomy and resection of their cancer if possible (78 patients) or no surgery (74 patients). Survival to each anniversary after randomization was very similar. After 5 years the survival rate was 8% for the group assigned to surgery and 6% for the group assigned to no surgery. The difference has a standard error of 4%.", "contents": "Preoperative irradiation of cancer of the lung: final report of a therapeutic trial. A collaborative study. Between May, 1963 and December, 1966, 17 medical centers cooperated in two separate but integrated therapeutic trials of primary lung cancer. One study was of patients with lesions considered operable at the time of diagnosis, and the other of patients with initially inoperable cancer but who were considered potentially operable after radiotherapy. Patients operable at the time of diagnosis were randomly assigned to receive either immediate surgery (278 patients) or preoperative radiotherapy followed by surgery (290 patients). All but one were followed until death or 5 years survival. Survival to each anniversary after randomization was almost identical for the two groups. At 5 years the survival rate was 14% after preoperative radiotherapy and 16% after immediate surgery. On the basis of the small standard error of the difference between these survival rates, a large advantage or a large disadvantage for preoperative radiotherapy is unlikely. Recurrence of cancer either locally or as distant metastasis was also similar in the two groups. Postoperative mortality was estimated to be 11% in the immediate surgery group, but cannot be estimated in a comparable fashion for the irradiated group. Certain postoperative complications were more frequent in the irradiated group, but survival during the first was not affected. Out of 425 patients initially considered to be inoperable, 152 were considered resectable after radiotherapy. These patients were randomly assigned to have either a thoracotomy and resection of their cancer if possible (78 patients) or no surgery (74 patients). Survival to each anniversary after randomization was very similar. After 5 years the survival rate was 8% for the group assigned to surgery and 6% for the group assigned to no surgery. The difference has a standard error of 4%."} {"id": "PMID:171058", "title": "Fractionation of nuclei and analysis of nuclear proteins of rat liver and Morris hepatoma 7777.", "content": "The contributions of nuclear populations to the total profile of nuclear proteins in a tissue were examined in normal rat liver and Morris hepatoma 7777. Comparison by sodium dodecyl sulfate polyacrylamide gel electrophoresis of phenol-soluble nuclear proteins from tumor and control liver revealed additional proteins of molecular weight 60,000, 100,00, and 135,000 and the loss of proteins of about 45,000 and 55,000 in the tumor. Subfractionation of liver nuclei on a 30 to 50% sucrose gradient yielded three nuclear classes with nearly identical complements of the phenol-soluble proteins. Similar fractionation performed on the hepatoma nuclei also produced three nuclear populations. In the hepatoma nuclei, several differences in the phenol-soluble proteins were found between the minor, slowly sedimenting nuclear fraction, and the two major fractions, while the two latter fractions were very similar in their protein composition. Histones derived from both tissues were also compared electrophoretically, indicating a decrease in the concentration of histone H1(0)in all nuclear classes derived from the tumor.", "contents": "Fractionation of nuclei and analysis of nuclear proteins of rat liver and Morris hepatoma 7777. The contributions of nuclear populations to the total profile of nuclear proteins in a tissue were examined in normal rat liver and Morris hepatoma 7777. Comparison by sodium dodecyl sulfate polyacrylamide gel electrophoresis of phenol-soluble nuclear proteins from tumor and control liver revealed additional proteins of molecular weight 60,000, 100,00, and 135,000 and the loss of proteins of about 45,000 and 55,000 in the tumor. Subfractionation of liver nuclei on a 30 to 50% sucrose gradient yielded three nuclear classes with nearly identical complements of the phenol-soluble proteins. Similar fractionation performed on the hepatoma nuclei also produced three nuclear populations. In the hepatoma nuclei, several differences in the phenol-soluble proteins were found between the minor, slowly sedimenting nuclear fraction, and the two major fractions, while the two latter fractions were very similar in their protein composition. Histones derived from both tissues were also compared electrophoretically, indicating a decrease in the concentration of histone H1(0)in all nuclear classes derived from the tumor."} {"id": "PMID:171059", "title": "Interaction of normal and tumor transfer RNA methyltransferases with ethionine-induced methyl-deficient rat liver transfer RNA.", "content": "The tRNA methyltransferases from normal rat liver and Novikoff hepatoma have been compared with respect to their base specificity, capacity to methylate, and reaction kinetics, using mixed Escherichia coli B transfer RNA (tRNA) and ethionine-induced partially methyl-deficient rat liver tRNA. The pattern of base methylation of the two substrates is different with the use of enzymes from either source. In particular, N1-methylguanine methylation is much greater in the methyl-deficient rat liver tRNA. The enzymes from the two sources also show differences in specificity of base methylation in either substrate, particularly in the percentage of N2-methylguanine synthesized. The Novikoff hepatoma enzymes have a greater capacity for methylation with either type of tRNA than do rat liver enzymes. The methyl-deficient rat liver tRNA is a poorer substrate for the enzymes from both sources than is E. coli B tRNA in terms of rate of methylation as well as total acceptance of methyl groups. The affinity constants are somewhat higher for the methyl-deficient rat liver tRNA than for E. coli B tRNA. The Novikoff hepatoma enzymes, in general, have larger affinity constants than the rat liver enzymes. Maximal velocities for the various base-specific enzymes are lower with the methyl-deficient rat liver tRNA, with the exception of the 1-methylguanine specific enzymes. These enzymes from either rat liver or Novikoff hepatoma exhibit approximately a 2.5-fold greater maximal velocity with methyl-deficient rat liver tRNA.", "contents": "Interaction of normal and tumor transfer RNA methyltransferases with ethionine-induced methyl-deficient rat liver transfer RNA. The tRNA methyltransferases from normal rat liver and Novikoff hepatoma have been compared with respect to their base specificity, capacity to methylate, and reaction kinetics, using mixed Escherichia coli B transfer RNA (tRNA) and ethionine-induced partially methyl-deficient rat liver tRNA. The pattern of base methylation of the two substrates is different with the use of enzymes from either source. In particular, N1-methylguanine methylation is much greater in the methyl-deficient rat liver tRNA. The enzymes from the two sources also show differences in specificity of base methylation in either substrate, particularly in the percentage of N2-methylguanine synthesized. The Novikoff hepatoma enzymes have a greater capacity for methylation with either type of tRNA than do rat liver enzymes. The methyl-deficient rat liver tRNA is a poorer substrate for the enzymes from both sources than is E. coli B tRNA in terms of rate of methylation as well as total acceptance of methyl groups. The affinity constants are somewhat higher for the methyl-deficient rat liver tRNA than for E. coli B tRNA. The Novikoff hepatoma enzymes, in general, have larger affinity constants than the rat liver enzymes. Maximal velocities for the various base-specific enzymes are lower with the methyl-deficient rat liver tRNA, with the exception of the 1-methylguanine specific enzymes. These enzymes from either rat liver or Novikoff hepatoma exhibit approximately a 2.5-fold greater maximal velocity with methyl-deficient rat liver tRNA."} {"id": "PMID:171060", "title": "The inhibition of ribosomal RNA synthesis and maturation in Novikoff hepatoma cells by 5-fluorouridine.", "content": "The inhibition of ribosomal RNA (rRNA) maturation by 5-fluorouridine (FUrd) in Novikoff hepatoma cells appears to depend upon the incorporation of the analog into the 45 S rRNA precursor. Precursor synthesized in the presence of FUrd is not processed into mature rRNA, but precursor synthesized in the absence of the analog is processed normally after the addition of the drug. The effect of FUrd on rRNA maturation is concentration dependent. At a concentration of 1 X 10(-4)M, the analog completely inhibits the formation of mature 18 S and 28 S rRNA; while at a concentration of 1 X 10(-7)M, the analog has no significant effect on rRNA maturation. These results suggest that some minimum degree of analog substitution is necessary to inhibit the maturation process. In addition to its inhibition of maturation, FUrd also inhibits the transcription of 45 S rRNA precursor. However, this effect of the drug is less complete and more time dependent that the effect on maturation. The inhibition of rRNA maturation by FUrd persists after removal of the analog from the culture medium. Cells that had been exposed to FUrd for 2 hr were unable to process 45 S rRNA precursor 20 hr after removal of the drug from the medium.", "contents": "The inhibition of ribosomal RNA synthesis and maturation in Novikoff hepatoma cells by 5-fluorouridine. The inhibition of ribosomal RNA (rRNA) maturation by 5-fluorouridine (FUrd) in Novikoff hepatoma cells appears to depend upon the incorporation of the analog into the 45 S rRNA precursor. Precursor synthesized in the presence of FUrd is not processed into mature rRNA, but precursor synthesized in the absence of the analog is processed normally after the addition of the drug. The effect of FUrd on rRNA maturation is concentration dependent. At a concentration of 1 X 10(-4)M, the analog completely inhibits the formation of mature 18 S and 28 S rRNA; while at a concentration of 1 X 10(-7)M, the analog has no significant effect on rRNA maturation. These results suggest that some minimum degree of analog substitution is necessary to inhibit the maturation process. In addition to its inhibition of maturation, FUrd also inhibits the transcription of 45 S rRNA precursor. However, this effect of the drug is less complete and more time dependent that the effect on maturation. The inhibition of rRNA maturation by FUrd persists after removal of the analog from the culture medium. Cells that had been exposed to FUrd for 2 hr were unable to process 45 S rRNA precursor 20 hr after removal of the drug from the medium."} {"id": "PMID:171061", "title": "Virus-like particles in cystic mammary adenoma of a snow leopard.", "content": "Virus-like particles were observed in the giant cells of a mammary adenoma of a snow leopard kept in captivity. Particles that measured 115 to 125 nm in diameter budded from the lamella of endoplasmic reticulum and were studded on their inner surfaces with dense granules (approximately 12 nm) that gave them their unique ultrastructural morphology. Such particles were not observed extracellularly. Type B or type C particles were not seen in the tumor tissue.", "contents": "Virus-like particles in cystic mammary adenoma of a snow leopard. Virus-like particles were observed in the giant cells of a mammary adenoma of a snow leopard kept in captivity. Particles that measured 115 to 125 nm in diameter budded from the lamella of endoplasmic reticulum and were studded on their inner surfaces with dense granules (approximately 12 nm) that gave them their unique ultrastructural morphology. Such particles were not observed extracellularly. Type B or type C particles were not seen in the tumor tissue."} {"id": "PMID:171062", "title": "Diminished binding of thyroid-stimulating hormone in a transplantable rat thyroid tumor as a possible cause of hormone unresponsiveness.", "content": "The adenylate cyclase activity and the binding of 125I-labeled thyroid-stimulating hormone (TSH) of normal and tumor rat thyroid plasma membranes were compared. No significant difference in the basal and fluoride-sensitive adenylate cyclase activity between normal and tumor plasma membranes was observed. Thyroid plasma membranes responded to TSH, whereas the enzyme from the tumor plasma membranes was TSH insensitive. Thyroid plasma membranes boud 125I-TSH. Tumor plasma membranes bound 125I-TSH poorly. At the highest concentration of unlabeled TSH used, 80% of the 125I-TSH that was bound to thyroid plasma membranes was displaced, whereas only 10% of the 125I-TSH bound to tumor plasma membranes was displaced. Therefore, it seems likely that the failure of this tumor to respond to TSH is due to an alteration in the functional unit of membrane adenylate cyclase at the level of the receptor subunit.", "contents": "Diminished binding of thyroid-stimulating hormone in a transplantable rat thyroid tumor as a possible cause of hormone unresponsiveness. The adenylate cyclase activity and the binding of 125I-labeled thyroid-stimulating hormone (TSH) of normal and tumor rat thyroid plasma membranes were compared. No significant difference in the basal and fluoride-sensitive adenylate cyclase activity between normal and tumor plasma membranes was observed. Thyroid plasma membranes responded to TSH, whereas the enzyme from the tumor plasma membranes was TSH insensitive. Thyroid plasma membranes boud 125I-TSH. Tumor plasma membranes bound 125I-TSH poorly. At the highest concentration of unlabeled TSH used, 80% of the 125I-TSH that was bound to thyroid plasma membranes was displaced, whereas only 10% of the 125I-TSH bound to tumor plasma membranes was displaced. Therefore, it seems likely that the failure of this tumor to respond to TSH is due to an alteration in the functional unit of membrane adenylate cyclase at the level of the receptor subunit."} {"id": "PMID:171063", "title": "The tissue culture and morphology of human breast tumor cell line BOT-2.", "content": "A continuous human breast tumor cell line (BOT-2) was derived from an infiltrating duct carcinoma. The tumor cell line was grown as a monolayer in flasks, but the cells could be readily adapted to growth in roller cultures. These studies indicate that BOT-2 cells have a 16- to 18-hr doubling time and a modal chromosomal number of 63. The original BOT-2 cell culture has been in continuous cultivation for almost 2 years and has been passed 137 times. The BOT-2 cell line has been differentiated from HeLa cells by isoenzyme studies and chromosomal analysis.", "contents": "The tissue culture and morphology of human breast tumor cell line BOT-2. A continuous human breast tumor cell line (BOT-2) was derived from an infiltrating duct carcinoma. The tumor cell line was grown as a monolayer in flasks, but the cells could be readily adapted to growth in roller cultures. These studies indicate that BOT-2 cells have a 16- to 18-hr doubling time and a modal chromosomal number of 63. The original BOT-2 cell culture has been in continuous cultivation for almost 2 years and has been passed 137 times. The BOT-2 cell line has been differentiated from HeLa cells by isoenzyme studies and chromosomal analysis."} {"id": "PMID:171064", "title": "Some biochemical characteristics of rat liver and Morris hepatoma nuclei and nuclear membranes.", "content": "Nuclei prepared from host liver and from Morris hepatomas 7777 and 7800 have been compared with respect to some of their biochemical characteristics. Several criteria were used to ensure that liver and hepatoma nuclei were of equal purity. These criteria include equal specific activity ratios (homogenate nuclei) for several marker enzymes. Phospholipids, proteins, and sialic acid content were compared in liver and hepatoma sucrose nuclei and in membrane and chromatin fractions obtained from liver or hepatoma nuclei. As determined by sodium dodecyl sulfate polyacrylamide electrophoresis, the only qualitative difference in protein that could detected was in 2 of the 4 nuclear fractions. There was an extra band in each of the 2 hepatoma fractions. Sialic acid was increased in hepatoma nuclei. In addition, a fraction containing most of the inner nuclear membrane from liver nuclei had no sialic acid, whereas the equivalent hepatoma fraction did have sialic acid. Total phospholipids were increased in hepatoma nuclei. This increased phospholipid concentration in hepatoma nuclei as compared to liver nuclei was apparent with sucrose nuclei, citric acid nuclei, membrane-denuded nuclei, chromatin, and nuclear fractions. Determination of the percentages of individual phospholipids making up the total phospholipids extracted revealed that the only significant change in the phospholipid composition of hepatoma nuclei was an increase in sphingomyelin. A large amount of this sphingomyelin was found to be associated with chromatin. The possible significance of chromatin-associated phospholipids is discussed.", "contents": "Some biochemical characteristics of rat liver and Morris hepatoma nuclei and nuclear membranes. Nuclei prepared from host liver and from Morris hepatomas 7777 and 7800 have been compared with respect to some of their biochemical characteristics. Several criteria were used to ensure that liver and hepatoma nuclei were of equal purity. These criteria include equal specific activity ratios (homogenate nuclei) for several marker enzymes. Phospholipids, proteins, and sialic acid content were compared in liver and hepatoma sucrose nuclei and in membrane and chromatin fractions obtained from liver or hepatoma nuclei. As determined by sodium dodecyl sulfate polyacrylamide electrophoresis, the only qualitative difference in protein that could detected was in 2 of the 4 nuclear fractions. There was an extra band in each of the 2 hepatoma fractions. Sialic acid was increased in hepatoma nuclei. In addition, a fraction containing most of the inner nuclear membrane from liver nuclei had no sialic acid, whereas the equivalent hepatoma fraction did have sialic acid. Total phospholipids were increased in hepatoma nuclei. This increased phospholipid concentration in hepatoma nuclei as compared to liver nuclei was apparent with sucrose nuclei, citric acid nuclei, membrane-denuded nuclei, chromatin, and nuclear fractions. Determination of the percentages of individual phospholipids making up the total phospholipids extracted revealed that the only significant change in the phospholipid composition of hepatoma nuclei was an increase in sphingomyelin. A large amount of this sphingomyelin was found to be associated with chromatin. The possible significance of chromatin-associated phospholipids is discussed."} {"id": "PMID:171065", "title": "Adhesion of malignant and nonmalignant cells to cultured embryonic substrates.", "content": "To study adhesion, which is probably the initial step in malignant invasion, we associated tissue culture fragments with living substrates in vitro. Malignant HeLa, hepatoma, and PY cells, as well as nonmalignant BHK cells, were transplanted into cultured chick blastoderms and organ fragments from chick embryos. Adhesion was evaluated by time-lapse cinematography, by flushing with Tyrode's solution, and by histological examination after fixation. It was shown that the adhesion of these tissue culture fragments depends on the nature of the substrate. Substrates of connective tissue, mesenchyme, and the basal side of epithelia proved to be adhesive. In contrast, the apical side of intact epithelia was nonadhesive. Perforated epithelia allowed adhesion at the site of the perforation. In the presence of dilysine, HeLa cells adhere to the apical side of epithelia and to the dorsal side of the upper layer of the blastoderm. We concluded that the apical side of intact epithelia constitutes an inappropriate substrate for adhesion of a large variety of cells, in vitro as well as in vivo. Alteration of this characteristic in the presence of dilysine indicates that long-range electrostatic repulsion might be responsible for the nonadhesive character of the epithelia.", "contents": "Adhesion of malignant and nonmalignant cells to cultured embryonic substrates. To study adhesion, which is probably the initial step in malignant invasion, we associated tissue culture fragments with living substrates in vitro. Malignant HeLa, hepatoma, and PY cells, as well as nonmalignant BHK cells, were transplanted into cultured chick blastoderms and organ fragments from chick embryos. Adhesion was evaluated by time-lapse cinematography, by flushing with Tyrode's solution, and by histological examination after fixation. It was shown that the adhesion of these tissue culture fragments depends on the nature of the substrate. Substrates of connective tissue, mesenchyme, and the basal side of epithelia proved to be adhesive. In contrast, the apical side of intact epithelia was nonadhesive. Perforated epithelia allowed adhesion at the site of the perforation. In the presence of dilysine, HeLa cells adhere to the apical side of epithelia and to the dorsal side of the upper layer of the blastoderm. We concluded that the apical side of intact epithelia constitutes an inappropriate substrate for adhesion of a large variety of cells, in vitro as well as in vivo. Alteration of this characteristic in the presence of dilysine indicates that long-range electrostatic repulsion might be responsible for the nonadhesive character of the epithelia."} {"id": "PMID:171066", "title": "Pathological review of breast lesions analyzed for estrogen receptor protein.", "content": "This report provides a detailed pathological review of 333 specimens analyzed for estrogen receptor protein (ERP) and correlates a series of morphological features with ERP results. Included were 147 primary breast carcinomas, 78 metastases, 27 fibroadenomas, and 81 nonneoplastic tissues, all from women. ERP in cytosols was assayed by incubation with [3H]estradiol in the presence and absence of \"cold\" estradiol followed by dextran-charcoal treatment. Results were summarized as positive (greater 60% inhibition by nontritiated estradiol, greater than 10 fmoles/mg protein), negative (less than 60% inhibition by nontritiated estradiol, less than 10 fmoles/mg protein), or intermediate borderline combinations. ERP in primary tumors ranged from 0.2 to 358 fmoles/mg protein (54.4% positive, 35.4% negative, 10.2% borderline). New findings are: (a) a high frequency of positive ERP in invasive lobular carcinoma (12 of 13, 92.3%) compared to typical ductal tumors (64 of 117, 54.7%); and (b) low frequency of positive ERP(5 of 21, 23.8%) in tumors with a prominent local lymphocyte reaction. Three ERP-positive noncarcinomatous specimens were fibroadenomas of high epithelial cellularity from patients under 30 years. No statistically significant relationship existed between ERP and any other morphological features that were examined.", "contents": "Pathological review of breast lesions analyzed for estrogen receptor protein. This report provides a detailed pathological review of 333 specimens analyzed for estrogen receptor protein (ERP) and correlates a series of morphological features with ERP results. Included were 147 primary breast carcinomas, 78 metastases, 27 fibroadenomas, and 81 nonneoplastic tissues, all from women. ERP in cytosols was assayed by incubation with [3H]estradiol in the presence and absence of \"cold\" estradiol followed by dextran-charcoal treatment. Results were summarized as positive (greater 60% inhibition by nontritiated estradiol, greater than 10 fmoles/mg protein), negative (less than 60% inhibition by nontritiated estradiol, less than 10 fmoles/mg protein), or intermediate borderline combinations. ERP in primary tumors ranged from 0.2 to 358 fmoles/mg protein (54.4% positive, 35.4% negative, 10.2% borderline). New findings are: (a) a high frequency of positive ERP in invasive lobular carcinoma (12 of 13, 92.3%) compared to typical ductal tumors (64 of 117, 54.7%); and (b) low frequency of positive ERP(5 of 21, 23.8%) in tumors with a prominent local lymphocyte reaction. Three ERP-positive noncarcinomatous specimens were fibroadenomas of high epithelial cellularity from patients under 30 years. No statistically significant relationship existed between ERP and any other morphological features that were examined."} {"id": "PMID:171069", "title": "Acute myocardial infarction in a young female with familial hyperbetalipoproteinemia.", "content": "A young woman, 21 years of age, suffered an acute transmural inferior wall myocardial infarction. EKG changes and serum enzymes accompanied a typical history. Coronary angiography perfomed 2 months after the acute episode showed complete occlusion of the right coronary artery and some mild disease of the circumflex and left anterior descending branches. Family history of type II hyperlipoproteinemia was present and she was known to have cholesterol since she was 12 years of age.", "contents": "Acute myocardial infarction in a young female with familial hyperbetalipoproteinemia. A young woman, 21 years of age, suffered an acute transmural inferior wall myocardial infarction. EKG changes and serum enzymes accompanied a typical history. Coronary angiography perfomed 2 months after the acute episode showed complete occlusion of the right coronary artery and some mild disease of the circumflex and left anterior descending branches. Family history of type II hyperlipoproteinemia was present and she was known to have cholesterol since she was 12 years of age."} {"id": "PMID:171070", "title": "The phosphorylation of nuclear proteins in the regenerating and premalignant rat liver and its significance for cell proliferation.", "content": "In liver regeneration or neoplastic transformation, phosphorylation of nuclear proteins is stimulated. In the regenerating liver all main histone fractions are involved in this process. The type of histone phosphorylated seems to be dependent on the position of the partially synchronized cells within the generation cycle. At a time when most cells are exhibiting maximum HnRNA-synthesis, histone F2a2 belongs to those fractions with highly stimulated phosphate incorporation. Phosphorylation of this fraction alone is stimulated by cyclic AMP in parallel to a stimulation of HnRNA-synthesis. The preneoplastic liver is characterized by oscillating phosphorylation and dephosphorylation reactions of nearly all histone fractions during the first days of N-nitroso-diethylamine administration. After 2 months of carcinogen feeding a 50-150% stimulation of the phosphorylation of Fl subfractions is observed. The phosphate content of the other histones, however, has returned to the original level. A series of further proteins, isolated together with the histones, show very similar phosphorylation characteristics. These proteins are mostly of non-histone origin. It is suggested that some of them are responsible for the transport of RNA with messenger properties within the cell.", "contents": "The phosphorylation of nuclear proteins in the regenerating and premalignant rat liver and its significance for cell proliferation. In liver regeneration or neoplastic transformation, phosphorylation of nuclear proteins is stimulated. In the regenerating liver all main histone fractions are involved in this process. The type of histone phosphorylated seems to be dependent on the position of the partially synchronized cells within the generation cycle. At a time when most cells are exhibiting maximum HnRNA-synthesis, histone F2a2 belongs to those fractions with highly stimulated phosphate incorporation. Phosphorylation of this fraction alone is stimulated by cyclic AMP in parallel to a stimulation of HnRNA-synthesis. The preneoplastic liver is characterized by oscillating phosphorylation and dephosphorylation reactions of nearly all histone fractions during the first days of N-nitroso-diethylamine administration. After 2 months of carcinogen feeding a 50-150% stimulation of the phosphorylation of Fl subfractions is observed. The phosphate content of the other histones, however, has returned to the original level. A series of further proteins, isolated together with the histones, show very similar phosphorylation characteristics. These proteins are mostly of non-histone origin. It is suggested that some of them are responsible for the transport of RNA with messenger properties within the cell."} {"id": "PMID:171071", "title": "Nuclear secretory particles associated with the calyx cells of the ichneumonid parasitoid Campoletis sonorensis (Cameron).", "content": "The present study is an ultrastructural investigation of the calyx region of the ichneumonid endoparasitoid Campoletis sonorensis. It appears that synthesis of electron-dense secretory particles occurs within nuclei of calyx cells. The particles consist of an ovocylindrical electron-dense inner core and a surrounding unit membrane. After their formation the particles pass from the nucleus by budding through both membranes of the nuclear envelope. The particles, along with fully developed parasitoid eggs concentrate within the lateral oviduct lumen. Feulgen histochemical studies suggest the presence of DNA within the calyxfluid. The possible function of the particles is discussed.", "contents": "Nuclear secretory particles associated with the calyx cells of the ichneumonid parasitoid Campoletis sonorensis (Cameron). The present study is an ultrastructural investigation of the calyx region of the ichneumonid endoparasitoid Campoletis sonorensis. It appears that synthesis of electron-dense secretory particles occurs within nuclei of calyx cells. The particles consist of an ovocylindrical electron-dense inner core and a surrounding unit membrane. After their formation the particles pass from the nucleus by budding through both membranes of the nuclear envelope. The particles, along with fully developed parasitoid eggs concentrate within the lateral oviduct lumen. Feulgen histochemical studies suggest the presence of DNA within the calyxfluid. The possible function of the particles is discussed."} {"id": "PMID:171073", "title": "Fine structure of the subradular organ of Lepidochitona cinereus (L), (Mollusca, Polyplacophora).", "content": "Electron microscopy of the subradular organ of the chiton Lepidochitona cinereus (L) reveals at least three cell types, microvillous, ciliated and mucus-secreting, situated in a single epithelium. The base of the epithelium is abundantly innervated and supplied with muscle cells. The fine structure is consistent with a chemosensory function for the subradular organ.", "contents": "Fine structure of the subradular organ of Lepidochitona cinereus (L), (Mollusca, Polyplacophora). Electron microscopy of the subradular organ of the chiton Lepidochitona cinereus (L) reveals at least three cell types, microvillous, ciliated and mucus-secreting, situated in a single epithelium. The base of the epithelium is abundantly innervated and supplied with muscle cells. The fine structure is consistent with a chemosensory function for the subradular organ."} {"id": "PMID:171072", "title": "Amphibian sympathetic ganglia in tissue culture.", "content": "1. A culture medium has been developed for amphibian sympathetic nervous tissue but it is suggested that the ionic values should be adjusted to correspond to the concentrations of salts in the plasma of particular species. 2. The morphology, monoamine fluorescence, growth and differentiation of sympathetic ganglia of the frog, Limnodynastes dumerili, have been studied in culture. 3. Two types of neuron could be distinguished largely according to size, namely small, 18 X 20 mum and large, 38 X 42 mum. The possibility that these represent one type at different stages in development or represent functionally distinct neurons is discussed. 4. The sympathetic neurons are extremely sensitive to nerve growth factor (NGF) which caused an increase in the size of the cell bodies, the number of nerve fibres regenerating, the rate of axonal growth and synthesis of catecholamines. 5. Various other cell types appearing in the cultures have been described, including chromaffin, satellite, Schwann, multipolar and epithelial cells as well as fibroblasts, melanocytes and macrophages. The epithelial cells show slow contractions and changes in shape.", "contents": "Amphibian sympathetic ganglia in tissue culture. 1. A culture medium has been developed for amphibian sympathetic nervous tissue but it is suggested that the ionic values should be adjusted to correspond to the concentrations of salts in the plasma of particular species. 2. The morphology, monoamine fluorescence, growth and differentiation of sympathetic ganglia of the frog, Limnodynastes dumerili, have been studied in culture. 3. Two types of neuron could be distinguished largely according to size, namely small, 18 X 20 mum and large, 38 X 42 mum. The possibility that these represent one type at different stages in development or represent functionally distinct neurons is discussed. 4. The sympathetic neurons are extremely sensitive to nerve growth factor (NGF) which caused an increase in the size of the cell bodies, the number of nerve fibres regenerating, the rate of axonal growth and synthesis of catecholamines. 5. Various other cell types appearing in the cultures have been described, including chromaffin, satellite, Schwann, multipolar and epithelial cells as well as fibroblasts, melanocytes and macrophages. The epithelial cells show slow contractions and changes in shape."} {"id": "PMID:171074", "title": "Synaptic morphology of the carotid body of the domestic fowl.", "content": "Efferent and reciprocal synapses have been demonstrated in the carotid body of the domestic fowl (Gallus gallus domesticus). Synapses were also found with purely afferent morphology, but were probably components of reciprocal synapses. The general morphology of the endings suggested the presence of two types of axon, afferent axons making reciprocal and perhaps afferent synapses with Type I cells, and efferent axons making efferent synapses with Type I cells. A few axo-dendritic synapses were also found. The dense-cored vesicles associated with the afferent components of reciprocal synapses and with the possible true afferent synapses varied in diameter and core but could belong to one population of pre-synaptic vesicles. These observations are consistent wtih a new theory for the carotid body receptor mechanism. This proposes a spontaneously discharging afferent axon inhibited by an inhibitory transmitter substance released by the Type I cell via the \"afferent\" component of its reciprocal synapse, the \"efferent\" component inhibiting this release. Besides this chemoreceptor modulation of its afferent axon, the Type I cell may also have a general secretory function.", "contents": "Synaptic morphology of the carotid body of the domestic fowl. Efferent and reciprocal synapses have been demonstrated in the carotid body of the domestic fowl (Gallus gallus domesticus). Synapses were also found with purely afferent morphology, but were probably components of reciprocal synapses. The general morphology of the endings suggested the presence of two types of axon, afferent axons making reciprocal and perhaps afferent synapses with Type I cells, and efferent axons making efferent synapses with Type I cells. A few axo-dendritic synapses were also found. The dense-cored vesicles associated with the afferent components of reciprocal synapses and with the possible true afferent synapses varied in diameter and core but could belong to one population of pre-synaptic vesicles. These observations are consistent wtih a new theory for the carotid body receptor mechanism. This proposes a spontaneously discharging afferent axon inhibited by an inhibitory transmitter substance released by the Type I cell via the \"afferent\" component of its reciprocal synapse, the \"efferent\" component inhibiting this release. Besides this chemoreceptor modulation of its afferent axon, the Type I cell may also have a general secretory function."} {"id": "PMID:171075", "title": "The ultrastructure, catecholamine, and prolactin contents of the rostral pars distalis of the fish Mugil platanus after reserpine or 6-hydroxydopamine administration.", "content": "The rostral pars distalis (RPD) of the teleost Mugil plantanus from animals pretreated with reserpine or 6-hydroxydopamine (6-HODA) were assayed for dopamine (DA) or noradrenaline (NA) or for prolactin hormone. Such determinations were coupled with electron microscopy. It was found that reserpine and 6-HODA produced a significant decrease in the content of DA, NA, and prolactin. Electron microscope studies revealed that prolactin cells became activated as judged by ultrastructural criteria. After 6-HODA treatment type \"B\" neurosecretory fibers entering the RPD became selectively destroyed. These observations lead us to suggest that prolactin secretion is under inhibitory control by type \"B\" neurosecretory fibers of adrenergic nature.", "contents": "The ultrastructure, catecholamine, and prolactin contents of the rostral pars distalis of the fish Mugil platanus after reserpine or 6-hydroxydopamine administration. The rostral pars distalis (RPD) of the teleost Mugil plantanus from animals pretreated with reserpine or 6-hydroxydopamine (6-HODA) were assayed for dopamine (DA) or noradrenaline (NA) or for prolactin hormone. Such determinations were coupled with electron microscopy. It was found that reserpine and 6-HODA produced a significant decrease in the content of DA, NA, and prolactin. Electron microscope studies revealed that prolactin cells became activated as judged by ultrastructural criteria. After 6-HODA treatment type \"B\" neurosecretory fibers entering the RPD became selectively destroyed. These observations lead us to suggest that prolactin secretion is under inhibitory control by type \"B\" neurosecretory fibers of adrenergic nature."} {"id": "PMID:171076", "title": "Nerve-ending specializations in the central ganglia of Planorbis corneus.", "content": "The neuropile in the central ganglia of Planorbis corneus was studied by electron microscopy, using different fixatives. Several types of specialization were observed in the membranes of adjacent axonal processes, varying from only slight membrane thickenings to structures resembling desmosomes. Specialized structures similar to the 'spinule complexes' in mammalian brain are widely distributed in certain areas of neuropile. They consist of a small projection which invaginates a neighbouring neurone; the membranes are closely apposed and there is associated electron-dense material. The problem of identifying chemical synapses in this tissue is discussed. Many axonal processes are varicose, and it is suggested that varicosities may also be sites of transmitter release.", "contents": "Nerve-ending specializations in the central ganglia of Planorbis corneus. The neuropile in the central ganglia of Planorbis corneus was studied by electron microscopy, using different fixatives. Several types of specialization were observed in the membranes of adjacent axonal processes, varying from only slight membrane thickenings to structures resembling desmosomes. Specialized structures similar to the 'spinule complexes' in mammalian brain are widely distributed in certain areas of neuropile. They consist of a small projection which invaginates a neighbouring neurone; the membranes are closely apposed and there is associated electron-dense material. The problem of identifying chemical synapses in this tissue is discussed. Many axonal processes are varicose, and it is suggested that varicosities may also be sites of transmitter release."} {"id": "PMID:171077", "title": "Ultrastructural and pharmacological studies on the afferent synapse of lateral-line sensory cells of the African clawed toad, Xenopus laevis.", "content": "Lateral-line sensory cells of Xenopus show considerable similarity to central nervous system synapses in their responses to the zinc iodide-osmium tetroxide, and bismuth-iodide cytochemical staining techniques. Both reserpine and FLA-63 cause a reduction in the diameter and electron density of the synaptic bars, and a dramatic loss of synaptic vesicles surrounding the bars. Aminooxy acetic acid and 3-mercaptopropionic acid cause no significant changes in the sensory-cell afferent synaptic apparatus. The results are discussed in the light of the known effects of the drugs. It is concluded that a monoamine rather than an amino acid may act as the afferent transmitter.", "contents": "Ultrastructural and pharmacological studies on the afferent synapse of lateral-line sensory cells of the African clawed toad, Xenopus laevis. Lateral-line sensory cells of Xenopus show considerable similarity to central nervous system synapses in their responses to the zinc iodide-osmium tetroxide, and bismuth-iodide cytochemical staining techniques. Both reserpine and FLA-63 cause a reduction in the diameter and electron density of the synaptic bars, and a dramatic loss of synaptic vesicles surrounding the bars. Aminooxy acetic acid and 3-mercaptopropionic acid cause no significant changes in the sensory-cell afferent synaptic apparatus. The results are discussed in the light of the known effects of the drugs. It is concluded that a monoamine rather than an amino acid may act as the afferent transmitter."} {"id": "PMID:171078", "title": "Ganglion cells and paraganglionic cells in the developing superior cervical ganglion of normal and p-chlorophenylalanine treated rats.", "content": "Ganglion cells and paraganglionic (PG) cells in the developing rat superior cervical ganglion were studied following postnatal treatment with p-chlorophenylalanine (pCPA) for 5 to 8 days. Litter mates, injected with saline solution, served as controls. Ganglion cells of control animals were differentiated ultrastructurally according to L. Er\u00e4nk\u00f6 (1972a) into late sympathicoblasts and young sympathetic nerve cells. In both maturation stages treatment with pCPA caused marked swelling of mitochondria, concomitant with minor changes of other cell organelles. Parallel to the ultrastructural alterations, fluorescence microscopy and cytophotometry revealed a slight diminution of diffuse fluorescence intensity in sympathetic neurons as the expression of a mainly extragranular amine depletion. In distinction from ganglion blocking agents the alterations are regarded as a general toxic effect of pCPA upon maturing sympathetic neurons, which secondarily influences catecholamine storage sites. Following treatment with pCPA, in PG-cells an alteration of mitochondria was scarcely to recognize. Specific granules were distinctly decreased in number, in some cases to an almost complete degree. Concordant to ultrastructural observations a marked diminution of fluorescence intensity was demonstrable in SIF-cells. In addition in these elements the fluorescence spectrum shifted towards the green field. Fluorescence cytophotometric evaluations confirmed the optical impression. Provided, that PG-cells, demonstrated with electron microscopy, are identical with SIF-cells in fluorescence microscopy, the results are discussed on the basis of a specific decrease of primary catecholamines due to an enzyme inhibition involved in catecholamine synthesis.", "contents": "Ganglion cells and paraganglionic cells in the developing superior cervical ganglion of normal and p-chlorophenylalanine treated rats. Ganglion cells and paraganglionic (PG) cells in the developing rat superior cervical ganglion were studied following postnatal treatment with p-chlorophenylalanine (pCPA) for 5 to 8 days. Litter mates, injected with saline solution, served as controls. Ganglion cells of control animals were differentiated ultrastructurally according to L. Er\u00e4nk\u00f6 (1972a) into late sympathicoblasts and young sympathetic nerve cells. In both maturation stages treatment with pCPA caused marked swelling of mitochondria, concomitant with minor changes of other cell organelles. Parallel to the ultrastructural alterations, fluorescence microscopy and cytophotometry revealed a slight diminution of diffuse fluorescence intensity in sympathetic neurons as the expression of a mainly extragranular amine depletion. In distinction from ganglion blocking agents the alterations are regarded as a general toxic effect of pCPA upon maturing sympathetic neurons, which secondarily influences catecholamine storage sites. Following treatment with pCPA, in PG-cells an alteration of mitochondria was scarcely to recognize. Specific granules were distinctly decreased in number, in some cases to an almost complete degree. Concordant to ultrastructural observations a marked diminution of fluorescence intensity was demonstrable in SIF-cells. In addition in these elements the fluorescence spectrum shifted towards the green field. Fluorescence cytophotometric evaluations confirmed the optical impression. Provided, that PG-cells, demonstrated with electron microscopy, are identical with SIF-cells in fluorescence microscopy, the results are discussed on the basis of a specific decrease of primary catecholamines due to an enzyme inhibition involved in catecholamine synthesis."} {"id": "PMID:171079", "title": "Evidence for the existence of two types of cAMP binding sites in aggregating cells of Dictyostelium discoideum.", "content": "Inhibition by dithiothreitol of the cell-bound phosphodiesterase has allowed the measurement of cAMP binding to aggregation-competent Dictyostelium discoidium amebae. Two classes of binding sites were demonstrated: Type 1, of low affinity (Kd approximately 160 nM) and high capacity (Ro approximately 1 X 10(5) sites per cell); and Type 2, of high affinity (Kd approximately 9 nM) but low capacity (Ro approximately 1.5 X 10(4) sites per cell). Both sites are developmentally regulated and are expressed during aggregation. The specificities of both sites are consistent with the specificity observed in vivo for the chemotactic response.", "contents": "Evidence for the existence of two types of cAMP binding sites in aggregating cells of Dictyostelium discoideum. Inhibition by dithiothreitol of the cell-bound phosphodiesterase has allowed the measurement of cAMP binding to aggregation-competent Dictyostelium discoidium amebae. Two classes of binding sites were demonstrated: Type 1, of low affinity (Kd approximately 160 nM) and high capacity (Ro approximately 1 X 10(5) sites per cell); and Type 2, of high affinity (Kd approximately 9 nM) but low capacity (Ro approximately 1.5 X 10(4) sites per cell). Both sites are developmentally regulated and are expressed during aggregation. The specificities of both sites are consistent with the specificity observed in vivo for the chemotactic response."} {"id": "PMID:171080", "title": "Effect of proteases on activation of resting chick embryo fibroblasts and on cell surface proteins.", "content": "The relationship between activation of resting chick embryo fibroblasts by proteases and proteolytic alteration of the cell surface has been investigated. Five different proteases were examined: trypsin, collagenase, plasmin, alpha-chymotrypsin, and thrombin. All of these proteases, when added to the culture medium at concentrations of 0.08-2.2 mug/ml, stimulated deoxyglucose uptake and induced cell division. The absolute levels of stimulation depended on the specific protease. Activation ranged from a doubling in cell number in 24 hr for trypsin and thrombin down to a 47% increase in cell number for alpha-chymotrypsin. Except in the case of thrombin, the stimulatory effects of these proteases correlated with breakdown of Z, a protein which is the major chick surface protein as revealed by lactoperoxidase-catalyzed iodination and which disappears upon transformation. In the case of thrombin, stimulatory concentrations brought about no detectable loss of surface components. Thus loss of Z is not a necessary condition for activation of chick fibroblasts; it may be a sufficient condition for activation of part of the cell population.", "contents": "Effect of proteases on activation of resting chick embryo fibroblasts and on cell surface proteins. The relationship between activation of resting chick embryo fibroblasts by proteases and proteolytic alteration of the cell surface has been investigated. Five different proteases were examined: trypsin, collagenase, plasmin, alpha-chymotrypsin, and thrombin. All of these proteases, when added to the culture medium at concentrations of 0.08-2.2 mug/ml, stimulated deoxyglucose uptake and induced cell division. The absolute levels of stimulation depended on the specific protease. Activation ranged from a doubling in cell number in 24 hr for trypsin and thrombin down to a 47% increase in cell number for alpha-chymotrypsin. Except in the case of thrombin, the stimulatory effects of these proteases correlated with breakdown of Z, a protein which is the major chick surface protein as revealed by lactoperoxidase-catalyzed iodination and which disappears upon transformation. In the case of thrombin, stimulatory concentrations brought about no detectable loss of surface components. Thus loss of Z is not a necessary condition for activation of chick fibroblasts; it may be a sufficient condition for activation of part of the cell population."} {"id": "PMID:171081", "title": "Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines.", "content": "Three Abelson virus-transformed lymphoma cell lines were established in tissue culture and the immunoglobulin biosynthesis by these cell lines was studied. Two of the cell lines (ABLS-1 and ABLS-5) were found to synthesize monomeric IgM molecules which were deposited in the cell membrane, probably to serve as an antigen receptor. The third cell line (ABLS-8) was found to synthesize membrane-associated IgM as well as cellular IgG molecules. In addition, these cell lines were found to synthesize a protein of 35,000 molecular weight which is also membrane-associated and which has the capability to bind the immunoglobulin (MAID). It is speculated that this protein might play a role in adapting the receptor immunoglobulin molecule to the hydrophobic environment of the cell membrane. The kinetics of amino acid incorporation into immunoglobulins by these cell lines show that they produce immunoglobulins at a rate which is two orders of magnitude smaller than plasmacytoma cells (MOPC 104E). These results suggest that Abelson virus transforms thymus-independent lymphocytes in various stages of maturation and these lymphocytes might be of B cell origin. The T lymphoma (P1798) used as a control cell line was found occasionally to produce minute amounts of immunoglobulin.", "contents": "Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines. Three Abelson virus-transformed lymphoma cell lines were established in tissue culture and the immunoglobulin biosynthesis by these cell lines was studied. Two of the cell lines (ABLS-1 and ABLS-5) were found to synthesize monomeric IgM molecules which were deposited in the cell membrane, probably to serve as an antigen receptor. The third cell line (ABLS-8) was found to synthesize membrane-associated IgM as well as cellular IgG molecules. In addition, these cell lines were found to synthesize a protein of 35,000 molecular weight which is also membrane-associated and which has the capability to bind the immunoglobulin (MAID). It is speculated that this protein might play a role in adapting the receptor immunoglobulin molecule to the hydrophobic environment of the cell membrane. The kinetics of amino acid incorporation into immunoglobulins by these cell lines show that they produce immunoglobulins at a rate which is two orders of magnitude smaller than plasmacytoma cells (MOPC 104E). These results suggest that Abelson virus transforms thymus-independent lymphocytes in various stages of maturation and these lymphocytes might be of B cell origin. The T lymphoma (P1798) used as a control cell line was found occasionally to produce minute amounts of immunoglobulin."} {"id": "PMID:171093", "title": "The activation of phospholipase C from Clostridium Welchii by quinine: an absolute requirement for calcium ions.", "content": "Quinine activates the hydrolysis of phosphatidyl choline suspensions by phospholipase C (E.C. 3.1.4.3) obtained from Clostridium welchii. Low levels of calcium are an absolute requirement for this activation: Mg2+, Ba2+, Sr2+, and Zn2+ are ineffective. The induction period, or lag phase for this enzyme is dependent upon both calcium concentration and substrate interfacial surface area. At low concentrations (less then 50 muM) calcium ions affect the induction period but not the maximal rate of hydrolysis, whereas guinine predominantly affects the rate of hydrolysis by alterations in the surface charge carried by the substrate.", "contents": "The activation of phospholipase C from Clostridium Welchii by quinine: an absolute requirement for calcium ions. Quinine activates the hydrolysis of phosphatidyl choline suspensions by phospholipase C (E.C. 3.1.4.3) obtained from Clostridium welchii. Low levels of calcium are an absolute requirement for this activation: Mg2+, Ba2+, Sr2+, and Zn2+ are ineffective. The induction period, or lag phase for this enzyme is dependent upon both calcium concentration and substrate interfacial surface area. At low concentrations (less then 50 muM) calcium ions affect the induction period but not the maximal rate of hydrolysis, whereas guinine predominantly affects the rate of hydrolysis by alterations in the surface charge carried by the substrate."} {"id": "PMID:171094", "title": "Phosphorus-31 studies on lecithin in ethanol solutions.", "content": "31P relaxation times of lecithin in ethanol solutions have been measured in dependence on temperature and water concentration. Trial calculations have been carried out on the assumption of a 2-site exchange model. The results suggest first, the relaxation behaviour is determined by various motional and exchange processes; second, at 29 MHz the dipole-dipole interaction between 31P and protons provides the dominant contribution; third, in general we are not concerned with the case of \"extreme narrowing\". Morover, there are no negligible intermolecular contributions to relaxation.", "contents": "Phosphorus-31 studies on lecithin in ethanol solutions. 31P relaxation times of lecithin in ethanol solutions have been measured in dependence on temperature and water concentration. Trial calculations have been carried out on the assumption of a 2-site exchange model. The results suggest first, the relaxation behaviour is determined by various motional and exchange processes; second, at 29 MHz the dipole-dipole interaction between 31P and protons provides the dominant contribution; third, in general we are not concerned with the case of \"extreme narrowing\". Morover, there are no negligible intermolecular contributions to relaxation."} {"id": "PMID:171095", "title": "[Comparative study on the ultrastructure of the primary mammary bud of male and female embryos at the stage of sexual differentiation].", "content": "The observation of embryonic mammary glands in male and female mice under the electron microscope has shown on one hand that the cellular ultrastructure of the buds is characterized by embryonic tissue only slightly differentiated, and on the other that, under the influence of testicular hormone, the detachment of the anlage from the epidermis in fourteen-day old embryos results in an important modification in the relationship between the ectoderm and the mesenchyme at the level of the neck of the gland rudiment. The basal membrane is destroyed and numerous centers of necrosis can be seen starting from the dense bodies in the ectodermic cells of the ruptured zone.", "contents": "[Comparative study on the ultrastructure of the primary mammary bud of male and female embryos at the stage of sexual differentiation]. The observation of embryonic mammary glands in male and female mice under the electron microscope has shown on one hand that the cellular ultrastructure of the buds is characterized by embryonic tissue only slightly differentiated, and on the other that, under the influence of testicular hormone, the detachment of the anlage from the epidermis in fourteen-day old embryos results in an important modification in the relationship between the ectoderm and the mesenchyme at the level of the neck of the gland rudiment. The basal membrane is destroyed and numerous centers of necrosis can be seen starting from the dense bodies in the ectodermic cells of the ruptured zone."} {"id": "PMID:171096", "title": "[Lipid overload induced in myocardial cells by vegetable oils. Observation using electron microscopy].", "content": "Comparative studies were made to estimate the lipid overloading of myocardiac cells in rats fed by groups, for 3 and 6 days, one of the following dietary oils: peanut oil, maize oil, sunflower oi, soyabean oil, rapeseed-primor oil, rapeseed-canbra oil and rapeseed oil.", "contents": "[Lipid overload induced in myocardial cells by vegetable oils. Observation using electron microscopy]. Comparative studies were made to estimate the lipid overloading of myocardiac cells in rats fed by groups, for 3 and 6 days, one of the following dietary oils: peanut oil, maize oil, sunflower oi, soyabean oil, rapeseed-primor oil, rapeseed-canbra oil and rapeseed oil."} {"id": "PMID:171097", "title": "[Ultrastructure of the rat neurohypophysis following electric stimulation of the supraoptic nuclei].", "content": "By means of electrical stimulation of the supraoptic nuclei, in a stereotaxic apparatus, partial or complete degranulation of the neurohypophysis is obtained, with often a continued presence of large vesicles; the number of microvesicles is always increased.", "contents": "[Ultrastructure of the rat neurohypophysis following electric stimulation of the supraoptic nuclei]. By means of electrical stimulation of the supraoptic nuclei, in a stereotaxic apparatus, partial or complete degranulation of the neurohypophysis is obtained, with often a continued presence of large vesicles; the number of microvesicles is always increased."} {"id": "PMID:171098", "title": "[A strain of amaril virus isolated from Aedes africanus in the Ivory Coast].", "content": "The yellow fever virus has been isolated from a pool of Aedes africanus caught on men in a region situated between forest and savannah near Touba, in the Ivory Coast. This isolation, occurring at an interepidemic period, proves for the first time in West Africa, the part played by this mosquito in the transmission of the yellow fever virus.", "contents": "[A strain of amaril virus isolated from Aedes africanus in the Ivory Coast]. The yellow fever virus has been isolated from a pool of Aedes africanus caught on men in a region situated between forest and savannah near Touba, in the Ivory Coast. This isolation, occurring at an interepidemic period, proves for the first time in West Africa, the part played by this mosquito in the transmission of the yellow fever virus."} {"id": "PMID:171099", "title": "Simplified Scatchard-plot assay for estrogen receptor in human breast tumor.", "content": "In this two-point Scatchard-plot assay, with which a test of competitive inhibition is combined, the sample is mechanically homogenized in a buffer containing dithiothreitol, ultracentrifuged to obtain a fat-free cytosol, the protein content of which is then adjusted, and free and bound labeled estradiol are separated with dextran-coated charcoal after overnight incubation. We tested the method for precision and reliability by assaying such cytosols from pregnant rabbit uteri before and after dilution with kidney cytosol, and by assaying several other target and nontarget animal and human tissues. The Scatchard plot data were more reliable than tests for percent inhibition of binding by a competitor (diethylstilbestrol). For a tumor tissue to be judged positive it must bind at least 8 fmol of estradiol per milligram of protein and have a Kd of 0.1 to 5 X 10(-10) mol/liter. Some non-target tissues showed less than 70% inhibition by 10(4)-fold concentrations (over labeled estradiol) of inhibitor. Of 19 breast-tumor specimens, seven were found to be positive.", "contents": "Simplified Scatchard-plot assay for estrogen receptor in human breast tumor. In this two-point Scatchard-plot assay, with which a test of competitive inhibition is combined, the sample is mechanically homogenized in a buffer containing dithiothreitol, ultracentrifuged to obtain a fat-free cytosol, the protein content of which is then adjusted, and free and bound labeled estradiol are separated with dextran-coated charcoal after overnight incubation. We tested the method for precision and reliability by assaying such cytosols from pregnant rabbit uteri before and after dilution with kidney cytosol, and by assaying several other target and nontarget animal and human tissues. The Scatchard plot data were more reliable than tests for percent inhibition of binding by a competitor (diethylstilbestrol). For a tumor tissue to be judged positive it must bind at least 8 fmol of estradiol per milligram of protein and have a Kd of 0.1 to 5 X 10(-10) mol/liter. Some non-target tissues showed less than 70% inhibition by 10(4)-fold concentrations (over labeled estradiol) of inhibitor. Of 19 breast-tumor specimens, seven were found to be positive."} {"id": "PMID:171101", "title": "Quantitation of estrogen receptors in human breast cancer by agar gel electrophoresis.", "content": "Samples from human primary and metastatic mammary carcinomas were examined for the presence of specific estrogen-binding proteins. Cytosols were incubated with [3H]estradiol-17beta with and without an excess of unlabelled estradiol or estrogen antagonist. After incubation, the mixtures were treated with dextran-charcoal to remove non-specifically bound steroid. Low-temperature agar gel electrophoresis was used to separate receptor- and non-receptor-bound steroid. Statistically significant differences were found between the tissue protein contents of primary mammary carcinomas and skin metastases. Estrogen receptor and tissue protein contents of the tumors seem to be related to the age of the patients. Objective remissions with endocrine therapy were obtained in patients with carcinomas which possessed a substantial concentration of estrogen receptors.", "contents": "Quantitation of estrogen receptors in human breast cancer by agar gel electrophoresis. Samples from human primary and metastatic mammary carcinomas were examined for the presence of specific estrogen-binding proteins. Cytosols were incubated with [3H]estradiol-17beta with and without an excess of unlabelled estradiol or estrogen antagonist. After incubation, the mixtures were treated with dextran-charcoal to remove non-specifically bound steroid. Low-temperature agar gel electrophoresis was used to separate receptor- and non-receptor-bound steroid. Statistically significant differences were found between the tissue protein contents of primary mammary carcinomas and skin metastases. Estrogen receptor and tissue protein contents of the tumors seem to be related to the age of the patients. Objective remissions with endocrine therapy were obtained in patients with carcinomas which possessed a substantial concentration of estrogen receptors."} {"id": "PMID:171102", "title": "Application of a simple urinary 11-deoxy-17-oxosteroid assay to the study of adrenocortical function in a selected group of hirsute women.", "content": "Using a relatively simple 11-deoxy-17-oxosteroid assay a group of hirsute patients have been studied before and following the administration of ACTH. These patients were selected on the basis that each showed an exaggerated response of urinary testosterone excretion to ACTH stimulation. Fifteen of eighteen patients were found to show an exaggerated urinary 11-deoxy-17-oxosteroid response to ACTH stimulation in addition to the excessive urinary testosterone response, suggesting that dysfunction of the adrenal cortex might be a factor contributing to the hirsutism of these fifteen patients.", "contents": "Application of a simple urinary 11-deoxy-17-oxosteroid assay to the study of adrenocortical function in a selected group of hirsute women. Using a relatively simple 11-deoxy-17-oxosteroid assay a group of hirsute patients have been studied before and following the administration of ACTH. These patients were selected on the basis that each showed an exaggerated response of urinary testosterone excretion to ACTH stimulation. Fifteen of eighteen patients were found to show an exaggerated urinary 11-deoxy-17-oxosteroid response to ACTH stimulation in addition to the excessive urinary testosterone response, suggesting that dysfunction of the adrenal cortex might be a factor contributing to the hirsutism of these fifteen patients."} {"id": "PMID:171104", "title": "A simple method for the determination of oestrogen receptor concentrations in breast tumours and other tissues.", "content": "A simple method for the determination of oestrogen receptor activity in breast tumours and other tissues is described. By competition between radioactive and non-radioactive oestradiol-17beta for binding to a tissue extract prepared with centrifugation at low speed, the presence or absence of receptors is decided from the unmanipulated data. The concentration of receptors (P0) and dissociation constant of binding (Kd) are calculated by Scatchard analysis. In two relatively homogeneous tissues, assay precision was of the order of 16% for receptor concentration and 21-33% for the dissociation constant of binding: in heterogeneous breast tumors, much poorer precision can be expected. Sensitivity determined empirically is approximately 0.1 fmol/mg tissue. The method has been applied to the determination of receptor concentrations in human breast cancers, benign breast tumours, non-malignant breast, gynaecomastic breast, and in various tissues of the rat. Receptor activity was detected in 70% of the human breast cancers examined, and in lower amounts, in 21% of the benign human breast tissues. Activity was also detected in rat uterus and mammary gland, and in low amounts in 82% of the rat mammary tumours analysed. Dissociation constant of binding was generally of the order of 0.5 x 10(-10) M. The advantages of the method are discussed.", "contents": "A simple method for the determination of oestrogen receptor concentrations in breast tumours and other tissues. A simple method for the determination of oestrogen receptor activity in breast tumours and other tissues is described. By competition between radioactive and non-radioactive oestradiol-17beta for binding to a tissue extract prepared with centrifugation at low speed, the presence or absence of receptors is decided from the unmanipulated data. The concentration of receptors (P0) and dissociation constant of binding (Kd) are calculated by Scatchard analysis. In two relatively homogeneous tissues, assay precision was of the order of 16% for receptor concentration and 21-33% for the dissociation constant of binding: in heterogeneous breast tumors, much poorer precision can be expected. Sensitivity determined empirically is approximately 0.1 fmol/mg tissue. The method has been applied to the determination of receptor concentrations in human breast cancers, benign breast tumours, non-malignant breast, gynaecomastic breast, and in various tissues of the rat. Receptor activity was detected in 70% of the human breast cancers examined, and in lower amounts, in 21% of the benign human breast tissues. Activity was also detected in rat uterus and mammary gland, and in low amounts in 82% of the rat mammary tumours analysed. Dissociation constant of binding was generally of the order of 0.5 x 10(-10) M. The advantages of the method are discussed."} {"id": "PMID:171109", "title": "Plasma lipoprotein abnormalities in a case of primary high-density lipoprotein (HDL) deficiency.", "content": "A 53-year-old patient with primary HDL-deficiency is reported. About 2% of the normal concentration of alpha1 HDL was present in his plasma. The alpha1-high-density-lipoproteins separated into two fast-moving components in polyacrylamide gel electrophoresis. The Apo HDL contained both the main apolipoproteins, Apo A-I and Apo A-II, but in disproportionally reduced amounts, the concentration of Apo A-I being reduced about 360-fold, and that of Apo A-II about 14-fold. Concomitantly, the amount of the Apo C polypeptides in the HDL-fractions was decreased to about 5.5% and the activity of the enzyme lecithin cholesterol acyltransferase (EC 2.3.1.4.3) in plasma was found to be only 40% of normal. Apoprotein D was present in the LDL in association with Apo B, forming an abnormal, fast-moving LDL-complex. Apo A-I and Apo A-II were both of normal size as determined by SDS-PAGE, and reduction with thiols resulted in the shift of the M.W. of Apo A-II from 17,000 daltons to about 8,500 daltons. Both proteins were found in the same position as their normal counterparts in analytical isoelectric focusing. The most likely explanation for the multiple lipoprotein abnormalities seems to be that a defect in the regulation or structure of Apo A-I is the basis of the HDL-deficeincy.", "contents": "Plasma lipoprotein abnormalities in a case of primary high-density lipoprotein (HDL) deficiency. A 53-year-old patient with primary HDL-deficiency is reported. About 2% of the normal concentration of alpha1 HDL was present in his plasma. The alpha1-high-density-lipoproteins separated into two fast-moving components in polyacrylamide gel electrophoresis. The Apo HDL contained both the main apolipoproteins, Apo A-I and Apo A-II, but in disproportionally reduced amounts, the concentration of Apo A-I being reduced about 360-fold, and that of Apo A-II about 14-fold. Concomitantly, the amount of the Apo C polypeptides in the HDL-fractions was decreased to about 5.5% and the activity of the enzyme lecithin cholesterol acyltransferase (EC 2.3.1.4.3) in plasma was found to be only 40% of normal. Apoprotein D was present in the LDL in association with Apo B, forming an abnormal, fast-moving LDL-complex. Apo A-I and Apo A-II were both of normal size as determined by SDS-PAGE, and reduction with thiols resulted in the shift of the M.W. of Apo A-II from 17,000 daltons to about 8,500 daltons. Both proteins were found in the same position as their normal counterparts in analytical isoelectric focusing. The most likely explanation for the multiple lipoprotein abnormalities seems to be that a defect in the regulation or structure of Apo A-I is the basis of the HDL-deficeincy."} {"id": "PMID:171110", "title": "Complement-induced mixed aggregation of T and B lymphocytes and myeloid cells and the effect of adjuvant.", "content": "Complement induces mixed aggregation of murine spleen cells bearing C3 receptors. In the present studies, we show with immunofluorescent techniques that these aggregates are formed by T and B lymphocytes and myeloid cells, B cells constituting the predominant component in normal mice. There are striking changes in the quantity and quality of the clumps after in vitro treatment with adjuvant, mostly due to an increase in macrophages and possibly in T cells. The possible meaning of these phenomena in T-cell-B-cell co-operation and in the mode of action of adjuvants is discussed.", "contents": "Complement-induced mixed aggregation of T and B lymphocytes and myeloid cells and the effect of adjuvant. Complement induces mixed aggregation of murine spleen cells bearing C3 receptors. In the present studies, we show with immunofluorescent techniques that these aggregates are formed by T and B lymphocytes and myeloid cells, B cells constituting the predominant component in normal mice. There are striking changes in the quantity and quality of the clumps after in vitro treatment with adjuvant, mostly due to an increase in macrophages and possibly in T cells. The possible meaning of these phenomena in T-cell-B-cell co-operation and in the mode of action of adjuvants is discussed."} {"id": "PMID:171111", "title": "Thymus transplantation. Reconstitution of cellular immunity in a four-year-old patient with T-cell deficiency.", "content": "The case is reported of a 4-year-old girl affected with recurrent infections; anaemia, thrombocytopenia, haemorrhages and hepatosplenomegaly. Immunological investigations revealed a defect in cellular immunity related to the thymus-dependent system, hypergammaglobulinaemia (especially of class IgE), and very high titres of antibodies against Epstein-Barr virus (EBV). After foetal thymus transplantation, correction of the immunological defect and significant clinical improvement were noted, as well as a decrease of IgE and EBV antibody titres.", "contents": "Thymus transplantation. Reconstitution of cellular immunity in a four-year-old patient with T-cell deficiency. The case is reported of a 4-year-old girl affected with recurrent infections; anaemia, thrombocytopenia, haemorrhages and hepatosplenomegaly. Immunological investigations revealed a defect in cellular immunity related to the thymus-dependent system, hypergammaglobulinaemia (especially of class IgE), and very high titres of antibodies against Epstein-Barr virus (EBV). After foetal thymus transplantation, correction of the immunological defect and significant clinical improvement were noted, as well as a decrease of IgE and EBV antibody titres."} {"id": "PMID:171117", "title": "Dermatoglyphics of congenital abnormalities without chromosomal aberrations. A review of the clinical applications.", "content": "This review outlines the dermatoglyphics of congenital abnormalities without chromosomal aberrations. When combined with other clinical features of a particular disease, dermatoglyphics can serve to strengthen a diagnostic impression and may be useful as a screening device to select individuals for additional diagnostic studies.", "contents": "Dermatoglyphics of congenital abnormalities without chromosomal aberrations. A review of the clinical applications. This review outlines the dermatoglyphics of congenital abnormalities without chromosomal aberrations. When combined with other clinical features of a particular disease, dermatoglyphics can serve to strengthen a diagnostic impression and may be useful as a screening device to select individuals for additional diagnostic studies."} {"id": "PMID:171131", "title": "[Raised cAMP content of striated muscle in experimental chronic renal failure (author's transl)].", "content": "3', 5'-Adenosine monophosphate (cAMP) levels were determined in skeletal and heart muscle tissue of rats in chronic renal failure. Compared to normal animals no alteration in cAMP concentration was observed in heart muscle, whereas the cAMP levels in skeletal muscle were increased by 34%. This cAMP rise may be caused by the elevated plasma catecholamines, glucagon or parathyroid hormone levels in uraemia. The results suggest that the increased cAMP levels in skeletal muscle of rats in chronic renal failure contribute to the raised cAMP levels in the plasma.", "contents": "[Raised cAMP content of striated muscle in experimental chronic renal failure (author's transl)]. 3', 5'-Adenosine monophosphate (cAMP) levels were determined in skeletal and heart muscle tissue of rats in chronic renal failure. Compared to normal animals no alteration in cAMP concentration was observed in heart muscle, whereas the cAMP levels in skeletal muscle were increased by 34%. This cAMP rise may be caused by the elevated plasma catecholamines, glucagon or parathyroid hormone levels in uraemia. The results suggest that the increased cAMP levels in skeletal muscle of rats in chronic renal failure contribute to the raised cAMP levels in the plasma."} {"id": "PMID:171132", "title": "[Plasma-aldosterone and renin activity in Bartter's syndrome (author's transl)].", "content": "The temporal changes of aldosterone concentration and renin activity in plasma under the influence of stimulating and inhibiting factors were tested in two patients with Bartter's syndrome. There was a normal response to potassium and sodium administration, spironolactone, angiotensin II, ACTH and dexamethasone. Changes in plasma-aldosterone concentration, as measured at frequent intervals during angiotensin II infusion, suggest differential regulation of aldosterone synthesis by angiotensin II. In one patient the symptoms improved with administration of glucocorticoid derivatives.", "contents": "[Plasma-aldosterone and renin activity in Bartter's syndrome (author's transl)]. The temporal changes of aldosterone concentration and renin activity in plasma under the influence of stimulating and inhibiting factors were tested in two patients with Bartter's syndrome. There was a normal response to potassium and sodium administration, spironolactone, angiotensin II, ACTH and dexamethasone. Changes in plasma-aldosterone concentration, as measured at frequent intervals during angiotensin II infusion, suggest differential regulation of aldosterone synthesis by angiotensin II. In one patient the symptoms improved with administration of glucocorticoid derivatives."} {"id": "PMID:171134", "title": "Nuclear binding capacity appears to limit the hepatic response to L-triiodothyronine (T3).", "content": "In vivo saturation studies of thyroidectomized, propyl thiouracil, and L-triiodothyronine treated animals indicate that the hepatic nuclear binding capacity is not significantly influenced by the thyroidal status of the tissues. The constancy of the nuclear binding capacity for L-triiodothyronine facilitated an analysis of the relationship between nuclear occupancy and hepatic response to an intravenous injection of a triiodothyronine pulse. The activity of the mitochondrial enzyme alpha-glycerophosphate dehydrogenase was used as an index of tissue response to the administered triiodothyronine. Results were compatible with the following model. Saturation of nuclear sites is rapidly followed by a maximal rate of enzyme synthesis. When the sites are saturated, the activity of alpha-glycerophosphate dehydrogenase appeared to be independent of the dose administered. Higher doses of triiodothyronine achieve greater effects simply by occupying nuclear sites for a longer period. The apparent ability of nuclear sites to constrain tissue response to hormone administration provides additional supporting data for the physiological relevance of these sites in the initiation of hormonal action.", "contents": "Nuclear binding capacity appears to limit the hepatic response to L-triiodothyronine (T3). In vivo saturation studies of thyroidectomized, propyl thiouracil, and L-triiodothyronine treated animals indicate that the hepatic nuclear binding capacity is not significantly influenced by the thyroidal status of the tissues. The constancy of the nuclear binding capacity for L-triiodothyronine facilitated an analysis of the relationship between nuclear occupancy and hepatic response to an intravenous injection of a triiodothyronine pulse. The activity of the mitochondrial enzyme alpha-glycerophosphate dehydrogenase was used as an index of tissue response to the administered triiodothyronine. Results were compatible with the following model. Saturation of nuclear sites is rapidly followed by a maximal rate of enzyme synthesis. When the sites are saturated, the activity of alpha-glycerophosphate dehydrogenase appeared to be independent of the dose administered. Higher doses of triiodothyronine achieve greater effects simply by occupying nuclear sites for a longer period. The apparent ability of nuclear sites to constrain tissue response to hormone administration provides additional supporting data for the physiological relevance of these sites in the initiation of hormonal action."} {"id": "PMID:171135", "title": "Androgen nuclear exchange activity in rat testis.", "content": "Androgen nuclear exchange activity has been measured in the rat testis. Exchange activity was increased 2-10-fold by pretreatment of the tissue with testosterone and persisted for at least 21 days after hypophysectomy in mature animals. Competition for exchange activity using 3H-testosterone or 3H-dihydrotestosterone was significant for a 500-fold excess of testosterone, dihydrotestosterone, progesterone, and cyproterone acetate. The activity was found in tubules and in isolated germ cells from mature rat testes. These results suggest that the molecular mechanism of androgen action in the testis may be quite complex and may involve components both in the more mature germ cells as well.", "contents": "Androgen nuclear exchange activity in rat testis. Androgen nuclear exchange activity has been measured in the rat testis. Exchange activity was increased 2-10-fold by pretreatment of the tissue with testosterone and persisted for at least 21 days after hypophysectomy in mature animals. Competition for exchange activity using 3H-testosterone or 3H-dihydrotestosterone was significant for a 500-fold excess of testosterone, dihydrotestosterone, progesterone, and cyproterone acetate. The activity was found in tubules and in isolated germ cells from mature rat testes. These results suggest that the molecular mechanism of androgen action in the testis may be quite complex and may involve components both in the more mature germ cells as well."} {"id": "PMID:171136", "title": "Prolactin binding activity on the crop sacs of juvenile, mature, parent and prolactin-injected pigeons.", "content": "Specific prolactin (PRL) binding activity of lactoperoxidase catalyzed 125I-labeled ovine-PRL was determined in a membrane-rich particulate fraction of pigeon crop sacs. Levels of TSH, LH or FSH as high as 1000 ng each were unable to displace the 125I-o-PRL bound to 600 mug of crop sac microsomal protein, whereas competitive displacement was achieved with as little as 0.5 ng unlabeled PRL. Ovine GH exhibited some cross reactivity when incubated in amounts greater than 500 ng, but this could be accounted for by its stated PRL contamination. Specific PRL binding activities were determined in juvenile and mature pigeons with unstimulated crop sacs, and parent pigeons with 'crop milk' and mature birds injected with PRL for 4 days. Crop sacs from juvenile birds contained approximately twice as much binding activity as crop sacs from mature pigeons. Parent and PRL injected pigeons, each with proliferated crop sac epithelium, exhibited 4-5 times as much specific PRL binding as the non-proliferated crops from juvenile or mature birds. These results show that the pigeon crop sac contains specific binding sites for PRL, and that the crop sac response to PRL is associated with an increase in PRL binding activity.", "contents": "Prolactin binding activity on the crop sacs of juvenile, mature, parent and prolactin-injected pigeons. Specific prolactin (PRL) binding activity of lactoperoxidase catalyzed 125I-labeled ovine-PRL was determined in a membrane-rich particulate fraction of pigeon crop sacs. Levels of TSH, LH or FSH as high as 1000 ng each were unable to displace the 125I-o-PRL bound to 600 mug of crop sac microsomal protein, whereas competitive displacement was achieved with as little as 0.5 ng unlabeled PRL. Ovine GH exhibited some cross reactivity when incubated in amounts greater than 500 ng, but this could be accounted for by its stated PRL contamination. Specific PRL binding activities were determined in juvenile and mature pigeons with unstimulated crop sacs, and parent pigeons with 'crop milk' and mature birds injected with PRL for 4 days. Crop sacs from juvenile birds contained approximately twice as much binding activity as crop sacs from mature pigeons. Parent and PRL injected pigeons, each with proliferated crop sac epithelium, exhibited 4-5 times as much specific PRL binding as the non-proliferated crops from juvenile or mature birds. These results show that the pigeon crop sac contains specific binding sites for PRL, and that the crop sac response to PRL is associated with an increase in PRL binding activity."} {"id": "PMID:171137", "title": "Cyclic AMP in the rat ovary: effect of endogenous LH secretion.", "content": "Cyclic AMP levels increased in ovaries from normal cycling rats on the afternoon of proestrus at the same time as the plasma LH peak occurred. Plasma progesterone was also elevated at this time. These results complement the extensive in vitro data indicating that cyclic AMP mediates the action of LH on the ovary.", "contents": "Cyclic AMP in the rat ovary: effect of endogenous LH secretion. Cyclic AMP levels increased in ovaries from normal cycling rats on the afternoon of proestrus at the same time as the plasma LH peak occurred. Plasma progesterone was also elevated at this time. These results complement the extensive in vitro data indicating that cyclic AMP mediates the action of LH on the ovary."} {"id": "PMID:171138", "title": "Hormone receptors, 5. Binding of glucagon and insulin to human circulating mononuclear cells in diabetes mellitus.", "content": "Preparations of human peripheral mononuclear leukocytes, containing over 85% lymphocytes, specifically bound glucagon and insulin. Binding of physiological concentrations of both hormones was seen to be substantially diminished when cells were derived from either adult-type diabetics or individuals with a unilateral genetic history of diabetes.", "contents": "Hormone receptors, 5. Binding of glucagon and insulin to human circulating mononuclear cells in diabetes mellitus. Preparations of human peripheral mononuclear leukocytes, containing over 85% lymphocytes, specifically bound glucagon and insulin. Binding of physiological concentrations of both hormones was seen to be substantially diminished when cells were derived from either adult-type diabetics or individuals with a unilateral genetic history of diabetes."} {"id": "PMID:171139", "title": "Some structural requirements for LH-RH actions.", "content": "LH-RH and analogues of LH-RH, [2-4] LH-RH, [Lys8] LH-RH, [Ala4] LH-RH and [3-10] LH-RH were tested in vitro for their ability to stimulate LH and FSH release, respectively. Furthermore, the influence of these peptides on binding of LH-RH to the anterior pituitary plasma membrane fractions of female rats was studied to obtain some information on the structural requirements for LH-RH actions. Significant increase of LH release above the control level was recorded for LH-RH, [Lys8] LH-RH and [Ala4] LH-RH. LH release in the presence of the tripeptide [2-4] LH-RH and the octapeptide [3-10] LH-RH was statistically indistinguishable from that of basal levels. Significant stimulation of FSH release was noted only in the presence of LH-RH and [Lys8] LH-RH. Changes in the binding characteristics of LH-RH to the pituitary plasma membrane in the presence of the LH-RH analogues suggest a proportionality between releasing ability and receptor affinity. Glu and His residues of the LH molecule were found to be critical for binding to the receptor. Residual binding ability of TRH to LH-RH receptor is consistent with current molecular models of LH-RH and TRH, respectively. Furthermore, the data presented suggest that the amino acid in position 8 of the LH-RH molecule is of importance for the three dimensional structure of LH-RH.", "contents": "Some structural requirements for LH-RH actions. LH-RH and analogues of LH-RH, [2-4] LH-RH, [Lys8] LH-RH, [Ala4] LH-RH and [3-10] LH-RH were tested in vitro for their ability to stimulate LH and FSH release, respectively. Furthermore, the influence of these peptides on binding of LH-RH to the anterior pituitary plasma membrane fractions of female rats was studied to obtain some information on the structural requirements for LH-RH actions. Significant increase of LH release above the control level was recorded for LH-RH, [Lys8] LH-RH and [Ala4] LH-RH. LH release in the presence of the tripeptide [2-4] LH-RH and the octapeptide [3-10] LH-RH was statistically indistinguishable from that of basal levels. Significant stimulation of FSH release was noted only in the presence of LH-RH and [Lys8] LH-RH. Changes in the binding characteristics of LH-RH to the pituitary plasma membrane in the presence of the LH-RH analogues suggest a proportionality between releasing ability and receptor affinity. Glu and His residues of the LH molecule were found to be critical for binding to the receptor. Residual binding ability of TRH to LH-RH receptor is consistent with current molecular models of LH-RH and TRH, respectively. Furthermore, the data presented suggest that the amino acid in position 8 of the LH-RH molecule is of importance for the three dimensional structure of LH-RH."} {"id": "PMID:171140", "title": "Sex steroids influence LH-RH-receptor interaction.", "content": "Intact male rats (I) and rats 30 days after orchidectomy (OR) were treated in vivo with a single dose of 1.5 or 0.5 mg testosterone propionate (TP), 22.5 or 7.5 mug estradiol benzoate (EB) and a mixture of TP plus EB, respectively. The release of LH and FSH from anterior pituitaries of steroid hormone pretreated animals induced by the administration of LH-RH was studied in vitro. LH-RH stimulated FSH release from pituitaries of I and OR was inhibited by higher doses of EB or a mixture of EB plus TP. On the other hand, EB and combination of EB plus TP stimulated LH release in I, whereas EB and TP inhibited LH-RH induced release of LH in OR. At the lower dose levels no inhibition of LH-RH stimulated FSH release from pituitaries of steroid pretreated I or OR animals occured. LH-RH induced LH release was only observed at thise dose level in I pretreated with TP and OR pretreated with EB. On the other hand, pretreatment of ovariectomized rats (OV) with sex steroids (5 mug 17 beta-estradiol, 3 mg progesterone, and mixture of 5 mug 17 beta-estradiol and 3 mg progesterone, resp., each injected through 6 days) resulted in restoration of LH-RH induced FSH release lost 30 days after ovariectomy. Furthermore, LH-RH induced release of LH and FSH from male rat pituitaries at different times after orc dectomy exhibited a pattern from that recorded for ovariectomized animals. [125I] LH-RH binding assays with anterior pituitary plasma membrane fractions isolated from I revealed two binding sites with apparent affinity constants of 4.3 x 10(-9) M and 2.2 x 10(-8) M, respectively. The low affinity binding site is lost upon orchidectomy. Scatchard plot analyses of binding data obtained for LH-RH reaction with plasma membrane fractions isolated from anterior pituitaries of OR pretreated with sex steroids showed that the second binding site could be regenerated by treatment with the low dose of TP. From the present experiments it is concluded that: 1. LH-RH induced gonadotropin release is affected by sex steroids at the pituitary plasma membrane level. 2. One hypothalamic hormone may well specifically control LH and FSH release. 3. Mechanisms controlling LH-RH induced gonadotropin release are different in the male and female.", "contents": "Sex steroids influence LH-RH-receptor interaction. Intact male rats (I) and rats 30 days after orchidectomy (OR) were treated in vivo with a single dose of 1.5 or 0.5 mg testosterone propionate (TP), 22.5 or 7.5 mug estradiol benzoate (EB) and a mixture of TP plus EB, respectively. The release of LH and FSH from anterior pituitaries of steroid hormone pretreated animals induced by the administration of LH-RH was studied in vitro. LH-RH stimulated FSH release from pituitaries of I and OR was inhibited by higher doses of EB or a mixture of EB plus TP. On the other hand, EB and combination of EB plus TP stimulated LH release in I, whereas EB and TP inhibited LH-RH induced release of LH in OR. At the lower dose levels no inhibition of LH-RH stimulated FSH release from pituitaries of steroid pretreated I or OR animals occured. LH-RH induced LH release was only observed at thise dose level in I pretreated with TP and OR pretreated with EB. On the other hand, pretreatment of ovariectomized rats (OV) with sex steroids (5 mug 17 beta-estradiol, 3 mg progesterone, and mixture of 5 mug 17 beta-estradiol and 3 mg progesterone, resp., each injected through 6 days) resulted in restoration of LH-RH induced FSH release lost 30 days after ovariectomy. Furthermore, LH-RH induced release of LH and FSH from male rat pituitaries at different times after orc dectomy exhibited a pattern from that recorded for ovariectomized animals. [125I] LH-RH binding assays with anterior pituitary plasma membrane fractions isolated from I revealed two binding sites with apparent affinity constants of 4.3 x 10(-9) M and 2.2 x 10(-8) M, respectively. The low affinity binding site is lost upon orchidectomy. Scatchard plot analyses of binding data obtained for LH-RH reaction with plasma membrane fractions isolated from anterior pituitaries of OR pretreated with sex steroids showed that the second binding site could be regenerated by treatment with the low dose of TP. From the present experiments it is concluded that: 1. LH-RH induced gonadotropin release is affected by sex steroids at the pituitary plasma membrane level. 2. One hypothalamic hormone may well specifically control LH and FSH release. 3. Mechanisms controlling LH-RH induced gonadotropin release are different in the male and female."} {"id": "PMID:171141", "title": "3,3',5'-Triiodothyronine (reverse T3) and 3,3',5-triiodothyronine (T3) in fetal and adult sheep: studies of metabolic clearance rates, production rates, serum binding, and thyroidal content relative to thyroxine.", "content": "To examine the mechanism(s) responsible for high serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) and low serum concentration of 3,3',5-triiodothyronine (T3) in the fetus, we studied metabolic clearance rates (MCR) and production rates (PR) of rT3, T3, and thyroxine (T4) in adult nonpregnant sheep and sheep fetuses in utero. The mean fetal MCR-rT3 was significantly lower than that in adult sheep, and the mean fetal PR-rT3 significantly higher. The mean fetal MCR-T3 was higher than, and the mean fetal PR-T3 similar to that in adult sheep. The mean fetal MCR-T4 and PR-T4 were both significantly higher than the corresponding values in adult sheep. The ratios of mean PR-rT3 to PR-T4 (rT3/T4) were similar in fetal and adult sheep. However, the ratio of mean PR-T3 to PR-T4 (T3/T4) in the fetal sheep was much lower than that in the adult sheep. The low fetal MCR-rT3 was not attributable to high serum binding of rT3. On the basis of the thyroidal content and kinetics of iodothyronines, it was estimated that whereas thyroidal secretion may account for nearly all of serum T3 (or PR-T3) in the fetus and about 50% of serum T3 in adults, it accounts for only about 3% of the serum rT3 (or PR-rT3) in both fetal and adult sheep. The results suggest a) that elevated serum rT3 in the fetus is due to its decreased clearance and increased production by mono-deiodination of T4, and b) that low serum T3 in the fetus is due to its increased clearance and decreased production by mono-deiodination of T4. In addition, on the basis of discordant changes in the production of T3 and rT3 from T4, it appears that there may exist two separate, apparently specific, iodothyronine deiodinating activities--one cleaving the iodine atom at the 5'-position and the other acting in the iodine atom at the 5-position of the T4 molecule; 5'-iodothyronine deiodinating activity is apparently reduced in the fetus.", "contents": "3,3',5'-Triiodothyronine (reverse T3) and 3,3',5-triiodothyronine (T3) in fetal and adult sheep: studies of metabolic clearance rates, production rates, serum binding, and thyroidal content relative to thyroxine. To examine the mechanism(s) responsible for high serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) and low serum concentration of 3,3',5-triiodothyronine (T3) in the fetus, we studied metabolic clearance rates (MCR) and production rates (PR) of rT3, T3, and thyroxine (T4) in adult nonpregnant sheep and sheep fetuses in utero. The mean fetal MCR-rT3 was significantly lower than that in adult sheep, and the mean fetal PR-rT3 significantly higher. The mean fetal MCR-T3 was higher than, and the mean fetal PR-T3 similar to that in adult sheep. The mean fetal MCR-T4 and PR-T4 were both significantly higher than the corresponding values in adult sheep. The ratios of mean PR-rT3 to PR-T4 (rT3/T4) were similar in fetal and adult sheep. However, the ratio of mean PR-T3 to PR-T4 (T3/T4) in the fetal sheep was much lower than that in the adult sheep. The low fetal MCR-rT3 was not attributable to high serum binding of rT3. On the basis of the thyroidal content and kinetics of iodothyronines, it was estimated that whereas thyroidal secretion may account for nearly all of serum T3 (or PR-T3) in the fetus and about 50% of serum T3 in adults, it accounts for only about 3% of the serum rT3 (or PR-rT3) in both fetal and adult sheep. The results suggest a) that elevated serum rT3 in the fetus is due to its decreased clearance and increased production by mono-deiodination of T4, and b) that low serum T3 in the fetus is due to its increased clearance and decreased production by mono-deiodination of T4. In addition, on the basis of discordant changes in the production of T3 and rT3 from T4, it appears that there may exist two separate, apparently specific, iodothyronine deiodinating activities--one cleaving the iodine atom at the 5'-position and the other acting in the iodine atom at the 5-position of the T4 molecule; 5'-iodothyronine deiodinating activity is apparently reduced in the fetus."} {"id": "PMID:171142", "title": "Thyroid-stimulating hormone regulation of ornithine decarboxylase activity in the thyroid.", "content": "TSH (1.0 U im) caused a 22-fold increase in thyroidal ornithine decarboxylase activity (ODC) 6 hours after administration in intact rats. Hypophysectomized rats treated with 1 U TSH showed a 5-fold increase in thyroid ODC activity. This stimulation appeared to be specific for TSH since hormones known to induce ODC activity in other target tissues, such as ACTH or LH, showed no significant stimulation. DIBUTYRYL CYCLIC AMP and aminopylline caused a 12-fold increase in ODC activity 5 hours after administration. Prostaglandins have also been implicated in the TSH-induced stimulation of cyclic AMP. Indomethacin (1.0 mg/100 g body wt, ip), an inhibitor of prostaglandin synthesis, was administered 3 hours before TSH with a resulting 30% diminution (P less than .001) in ODC activity compared with the administration of TSH alone. To rule out the possibility that the increase in ODC activity with TSH might be due to increased thyroid hormone secretion, ODC activity was evaluated 6 hours after triiodothyronine administration (60 mug/100 g body wt), and no significant increase in thyroid ODC activity was found. Stimulation of ODC activity was 90% inhibited by the intraperitoneal administration of actinomycin D (80 mug/100 g body wt) or cycloheximide (400 mug/100 g body wt) given simultaneously with TSH. These results indicated that TSH specifically stimulated thyroid ODC activity, which may be important for the growth-promoting action of the hormone on the thyroid gland. This action may be mediated by cAMP and prostaglandins and may require new protein synthesis.", "contents": "Thyroid-stimulating hormone regulation of ornithine decarboxylase activity in the thyroid. TSH (1.0 U im) caused a 22-fold increase in thyroidal ornithine decarboxylase activity (ODC) 6 hours after administration in intact rats. Hypophysectomized rats treated with 1 U TSH showed a 5-fold increase in thyroid ODC activity. This stimulation appeared to be specific for TSH since hormones known to induce ODC activity in other target tissues, such as ACTH or LH, showed no significant stimulation. DIBUTYRYL CYCLIC AMP and aminopylline caused a 12-fold increase in ODC activity 5 hours after administration. Prostaglandins have also been implicated in the TSH-induced stimulation of cyclic AMP. Indomethacin (1.0 mg/100 g body wt, ip), an inhibitor of prostaglandin synthesis, was administered 3 hours before TSH with a resulting 30% diminution (P less than .001) in ODC activity compared with the administration of TSH alone. To rule out the possibility that the increase in ODC activity with TSH might be due to increased thyroid hormone secretion, ODC activity was evaluated 6 hours after triiodothyronine administration (60 mug/100 g body wt), and no significant increase in thyroid ODC activity was found. Stimulation of ODC activity was 90% inhibited by the intraperitoneal administration of actinomycin D (80 mug/100 g body wt) or cycloheximide (400 mug/100 g body wt) given simultaneously with TSH. These results indicated that TSH specifically stimulated thyroid ODC activity, which may be important for the growth-promoting action of the hormone on the thyroid gland. This action may be mediated by cAMP and prostaglandins and may require new protein synthesis."} {"id": "PMID:171143", "title": "The prosence of estrogen receptor in kidneys from normal and androgen-insensitive tfm/y mice.", "content": "In vitro and in vivo binding of [3H]estradiol to cytosol proteins and nuclei was studied in kidneys from normal and androgen-insensitive tfm/y mice. The use of tfm/y mice permitted study of the estrogen-receptor complex in the absence of androgen receptor. A high affinity, [3H]estradiol-labeled, 8S molecule was demonstrated in low salt sucrose gradients. This macromolecule sedimented more slowly in gradients containing KC1 (0.5 M). Binding of [3H]estradiol was inhibited by 100-fold excess estrone, estradiol, or diethylstillbestrol but was not affected by testosterone, androstenedione, or progesterone. Studies of equilibrium-binding kinetics for estradiol indicated a Kd of 1.4 X 10(-9) M and 4.4 X 10(-14) mol of binding sites/mg cytosol protein. Furthermore, the binder was an acidic, heat-labile protein (pI = 4.8) which could be precipitated from cytosol with 33% ammonium sulfate, and needed sulfhydryl groups for activity. The demonstration of an estradiol-binding protein in vitro was correlated with specific [3H]estradiol uptake by tfm/y kidney nuclei in vivo. We concluded that the mouse kidney contains an estradiol-binding protein, distinct from that for androgens, which has many of the characteristics of a steroid receptor. The presence of an estrogen receptor in both normal and tfm/y mice indicates that a genetic defect in one receptor does not influence the properties of another. We concluded that androgen and estrogen receptors are under independent genetic control.", "contents": "The prosence of estrogen receptor in kidneys from normal and androgen-insensitive tfm/y mice. In vitro and in vivo binding of [3H]estradiol to cytosol proteins and nuclei was studied in kidneys from normal and androgen-insensitive tfm/y mice. The use of tfm/y mice permitted study of the estrogen-receptor complex in the absence of androgen receptor. A high affinity, [3H]estradiol-labeled, 8S molecule was demonstrated in low salt sucrose gradients. This macromolecule sedimented more slowly in gradients containing KC1 (0.5 M). Binding of [3H]estradiol was inhibited by 100-fold excess estrone, estradiol, or diethylstillbestrol but was not affected by testosterone, androstenedione, or progesterone. Studies of equilibrium-binding kinetics for estradiol indicated a Kd of 1.4 X 10(-9) M and 4.4 X 10(-14) mol of binding sites/mg cytosol protein. Furthermore, the binder was an acidic, heat-labile protein (pI = 4.8) which could be precipitated from cytosol with 33% ammonium sulfate, and needed sulfhydryl groups for activity. The demonstration of an estradiol-binding protein in vitro was correlated with specific [3H]estradiol uptake by tfm/y kidney nuclei in vivo. We concluded that the mouse kidney contains an estradiol-binding protein, distinct from that for androgens, which has many of the characteristics of a steroid receptor. The presence of an estrogen receptor in both normal and tfm/y mice indicates that a genetic defect in one receptor does not influence the properties of another. We concluded that androgen and estrogen receptors are under independent genetic control."} {"id": "PMID:171144", "title": "Androgen induction of a specific uterine protein.", "content": "Studies were conducted to determine the ability of androgens in vitro to elicit the induction of a specific uterine protein (IP) normally attributed to estrogens. Both 5alpha-dihydrotestosterone (5alpha-DHT) and testosterone were effective in stimulating IP synthesis in rat uterine tissue in a concentration dependent manner (0.1 muM to 50 muM). 5alpha-DHT was more effective than testosterone and reached approximately 85% of the estradiol stimulated IP response at 10 muM and 50 muM; whereas testosterone was only able to achieve about a 70% IP response at 50 muM. This androgen stimulated IP synthesis was stereospecific since cis-testosterone and 5beta-DHT, inactive androgen isomers, were unable to evoke a detectable IP response at any concentration studied. Antiandrogens were unable to inhibit the 5alpha-DHT stimulated IP synthesis but antiestrogens were able to greatly inhibit the 5alpha-DHT and testosterone stimulated IP responses in a concentration dependent manner. The anti-estrogens, themselves, were very weak inducers of the IP response. The nuclear accumulation of the estrogen receptor by various androgens and inactive androgen isomers was also determined. Approximately 100% nuclear accumulation of receptor was attained with 1 muM 5alpha-DHT, whereas 50 muM testosterone was needed for 100% uptake. 5beta-DHT was unable to translocate the receptor at the lower concentrations tested, but caused a significant nuclear accumulation of 50 muM. Cis-testosterone was unable to cause the nuclear accumulation of the estrogen receptor at all concentrations studied. These studies suggest that some of the estrogen receptors accumulated in the nuclei by androgens, inactive androgen isomers, or antiestrogens may not be capable of eliciting a biological response.", "contents": "Androgen induction of a specific uterine protein. Studies were conducted to determine the ability of androgens in vitro to elicit the induction of a specific uterine protein (IP) normally attributed to estrogens. Both 5alpha-dihydrotestosterone (5alpha-DHT) and testosterone were effective in stimulating IP synthesis in rat uterine tissue in a concentration dependent manner (0.1 muM to 50 muM). 5alpha-DHT was more effective than testosterone and reached approximately 85% of the estradiol stimulated IP response at 10 muM and 50 muM; whereas testosterone was only able to achieve about a 70% IP response at 50 muM. This androgen stimulated IP synthesis was stereospecific since cis-testosterone and 5beta-DHT, inactive androgen isomers, were unable to evoke a detectable IP response at any concentration studied. Antiandrogens were unable to inhibit the 5alpha-DHT stimulated IP synthesis but antiestrogens were able to greatly inhibit the 5alpha-DHT and testosterone stimulated IP responses in a concentration dependent manner. The anti-estrogens, themselves, were very weak inducers of the IP response. The nuclear accumulation of the estrogen receptor by various androgens and inactive androgen isomers was also determined. Approximately 100% nuclear accumulation of receptor was attained with 1 muM 5alpha-DHT, whereas 50 muM testosterone was needed for 100% uptake. 5beta-DHT was unable to translocate the receptor at the lower concentrations tested, but caused a significant nuclear accumulation of 50 muM. Cis-testosterone was unable to cause the nuclear accumulation of the estrogen receptor at all concentrations studied. These studies suggest that some of the estrogen receptors accumulated in the nuclei by androgens, inactive androgen isomers, or antiestrogens may not be capable of eliciting a biological response."} {"id": "PMID:171145", "title": "LH-hCG receptors and testosterone content during differentiation of the testis in the rabbit embryo.", "content": "The development of gonadotropin receptors for LH and hCG in the fetal rabbit testis from 17-29 days of gestation was followed by quantitative binding studies with [125I]iodohCG and compared with gonadal testosterone content and the histological differentiation of the fetal Leydig cells. The concentrations of gonadotropin receptors and testosterone in the fetal testis were low on days 17 and 18 and increased strikingly on day 19. This time sequence for development of LH-hCG receptors and steroid content of the testis was correlated exactly with the histological appearance of the endoplasmic reticulum characteristic of the differentiated Leydig cell. When fetal testes were examined at 12-h intervals between days 17 and 19, gonadotropin binding and testosterone content were closely correlated at all times studied. Thus, no dissociation between the two functions was demonstrable in the testis at any time during gestation. In the fetal ovary, LH-hCG binding and testosterone content were low or undetectable at all stages of gestation. These observations demonstrate a close temporal relationship between the appearance of the LH-hCG receptor and the synthesis of testosterone by the fetal testis and demonstrate that the histological and functional differentiation of the Leydig cell occurs within a few hours at approximately day 18 of gestation. The simultaneous appearance of LH-hCG receptors and testosterone synthesis in the gonad can be regarded as the biochemical manifestations of Leydig cell differentiation in the testis of the fetal rabbit.", "contents": "LH-hCG receptors and testosterone content during differentiation of the testis in the rabbit embryo. The development of gonadotropin receptors for LH and hCG in the fetal rabbit testis from 17-29 days of gestation was followed by quantitative binding studies with [125I]iodohCG and compared with gonadal testosterone content and the histological differentiation of the fetal Leydig cells. The concentrations of gonadotropin receptors and testosterone in the fetal testis were low on days 17 and 18 and increased strikingly on day 19. This time sequence for development of LH-hCG receptors and steroid content of the testis was correlated exactly with the histological appearance of the endoplasmic reticulum characteristic of the differentiated Leydig cell. When fetal testes were examined at 12-h intervals between days 17 and 19, gonadotropin binding and testosterone content were closely correlated at all times studied. Thus, no dissociation between the two functions was demonstrable in the testis at any time during gestation. In the fetal ovary, LH-hCG binding and testosterone content were low or undetectable at all stages of gestation. These observations demonstrate a close temporal relationship between the appearance of the LH-hCG receptor and the synthesis of testosterone by the fetal testis and demonstrate that the histological and functional differentiation of the Leydig cell occurs within a few hours at approximately day 18 of gestation. The simultaneous appearance of LH-hCG receptors and testosterone synthesis in the gonad can be regarded as the biochemical manifestations of Leydig cell differentiation in the testis of the fetal rabbit."} {"id": "PMID:171146", "title": "Estradiol receptor content in rat granulosa cells during follicular development: modification by estradiol and gonadotropins.", "content": "To examine the relationships between gonadotropic hormones, ovarian follicular development, and estradiol receptor content in rat granulosa cells, follicular growth was stimulated in intact immature rats and hypophysectomized immature rats. In intact rats, both PMSG and oFSH given for 2 days stimulated follicular growth and endogenous estrogen production but caused estradiol receptor content in granulosa cells to decrease markedly. In hypophysectomized rats estradiol (2 mg/day X 4) was capable of increasing the content of its own receptor, stimulated preantral follicular development, and potentiated the responses of granulosa cells to highly purified hFSH. Thus, subsequent treatment with hFSH stimulated antral formation and maintained high levels of estradiol receptor content in granulosa cells. LH, on the other hand, caused a rapid decline in the content of estradiol receptor in nuclei of granulosa cells. In hypophysectomized rats primed with estradiol alone, a high dose of oLH caused follicles to undergo atresia. In hypophysectomized rats primed with hFSH in addition to estradiol, oLH stimulated luteinization. Thus, induction of atresia or luteinization by oLH in these rats appears to be associated (cause or effect?) with a loss of estradiol receptor in granulosa cells. Whether follicles of estrogen-treated, hypophysectomized rats luteinize or undergo atresia in response to LH appears to be determined by their stage of differentiation and the nature of the prior stimulation by FSH.", "contents": "Estradiol receptor content in rat granulosa cells during follicular development: modification by estradiol and gonadotropins. To examine the relationships between gonadotropic hormones, ovarian follicular development, and estradiol receptor content in rat granulosa cells, follicular growth was stimulated in intact immature rats and hypophysectomized immature rats. In intact rats, both PMSG and oFSH given for 2 days stimulated follicular growth and endogenous estrogen production but caused estradiol receptor content in granulosa cells to decrease markedly. In hypophysectomized rats estradiol (2 mg/day X 4) was capable of increasing the content of its own receptor, stimulated preantral follicular development, and potentiated the responses of granulosa cells to highly purified hFSH. Thus, subsequent treatment with hFSH stimulated antral formation and maintained high levels of estradiol receptor content in granulosa cells. LH, on the other hand, caused a rapid decline in the content of estradiol receptor in nuclei of granulosa cells. In hypophysectomized rats primed with estradiol alone, a high dose of oLH caused follicles to undergo atresia. In hypophysectomized rats primed with hFSH in addition to estradiol, oLH stimulated luteinization. Thus, induction of atresia or luteinization by oLH in these rats appears to be associated (cause or effect?) with a loss of estradiol receptor in granulosa cells. Whether follicles of estrogen-treated, hypophysectomized rats luteinize or undergo atresia in response to LH appears to be determined by their stage of differentiation and the nature of the prior stimulation by FSH."} {"id": "PMID:171147", "title": "The effect on gastrin secretion of agents which increase the intracellular concentration of 3',5'-adenosine monophosphate.", "content": "An in vitro technique that allows study of gastrin secretion from isolated pieces of rat gastric antrum was used to study the effect on gastrin release of agents known to increase intracellular cAMP levels. Isuprel (10(-5)M), PGE1 (10(-5)M), theophylline (10(-4)M), and dibutyryl cAMP (5 X 10(-4)M) did not affect gastrin release when used alone, but each enhanced arginine-stimulated gastrin release. A biphasic pattern of gastrin release in response to arginine was seen in all experiments. The studies emphasize the close functional similarity between the antral G cells and the B cells of the pancreatic islet.", "contents": "The effect on gastrin secretion of agents which increase the intracellular concentration of 3',5'-adenosine monophosphate. An in vitro technique that allows study of gastrin secretion from isolated pieces of rat gastric antrum was used to study the effect on gastrin release of agents known to increase intracellular cAMP levels. Isuprel (10(-5)M), PGE1 (10(-5)M), theophylline (10(-4)M), and dibutyryl cAMP (5 X 10(-4)M) did not affect gastrin release when used alone, but each enhanced arginine-stimulated gastrin release. A biphasic pattern of gastrin release in response to arginine was seen in all experiments. The studies emphasize the close functional similarity between the antral G cells and the B cells of the pancreatic islet."} {"id": "PMID:171148", "title": "A sensitive and simple in vitro assay for corticotropin-releasing substances utilizing ACTH release from cultured anterior pituitary cells.", "content": "Graded doses of rat hypothalamic extract (HE) were added to dishes containing dispersed, pooled rat adenohypophyseal cells cultured for several days. ACTH secretion into the medium gave a linear log-dose response curve over a 100-fold range between 0.01 and 1 mg of NIH-HE (0.0125-1.25 rat hypothalamus). Forty percent of the maximal ACTH secretion in response to a given dose of HE occurred within 3 min. No decrease in intracellular ACTH occurred at any time or with any dose of HE, indicating that secretion was always balanced by production. ACTH secretion stopped as soon as HE-containing medium was replaced by medium without HE. The same cultured cells could be satisfactorily used in repetitive assays performed on the same or different days.", "contents": "A sensitive and simple in vitro assay for corticotropin-releasing substances utilizing ACTH release from cultured anterior pituitary cells. Graded doses of rat hypothalamic extract (HE) were added to dishes containing dispersed, pooled rat adenohypophyseal cells cultured for several days. ACTH secretion into the medium gave a linear log-dose response curve over a 100-fold range between 0.01 and 1 mg of NIH-HE (0.0125-1.25 rat hypothalamus). Forty percent of the maximal ACTH secretion in response to a given dose of HE occurred within 3 min. No decrease in intracellular ACTH occurred at any time or with any dose of HE, indicating that secretion was always balanced by production. ACTH secretion stopped as soon as HE-containing medium was replaced by medium without HE. The same cultured cells could be satisfactorily used in repetitive assays performed on the same or different days."} {"id": "PMID:171149", "title": "Inhibition of the response of mouse thyroid to tryrotropin induced by chronic triiodothyronine treatment.", "content": "Administration of 1 mU bovine TSH iv to mice resulted, within 1 hour, in the increase of the serum T4 level from 32 +/- 1.4 ng/ml to 53 +/- 2.6 ng/ml (Mean +/- SE, n = 24). Treatment with 1 mug triiodothyronine (T3) per day, for 10 days, abolished the responsiveness of the thyroid to TSH, as measured by thyroxine (T4) release. Thyroidal response to TSH was measured also in vitro. The basal hormonal release was 4.66 +/- 0.55 ng T4 and 0.98 +/- 0.15 ng T3 per thyroid per 3 h (n = 30). In the presence of bovine TSH (0.2 mU/ml) the hormonal secretion increased 3-fold for T4 and 2.5-fold for T3. Thyroids from mice pretreated with T3 for 10 days showed almost no response to TSH. Partial refractoriness to TSH was already significant 5 days after T3 pretreatment. Responsiveness to TSH was restored 3 days after T3 withdrawal or after 3 daily injections of 10 mU bovine TSH, concomitant with the last 3 days of T3 pretreatment. These results indicated that the prolonged absence of an adequate level of trophic hormone may be the cause of thyroidal unresponsiveness to acute TSH treatment. With 20 mU of TSH, cAMP levels rose from 4 +/- 0.5 picomoles to 80 +/- 9.3 picomoles per thyroid (n = 6). In mice subjected to 10 days of T3 pretreatment the response was markedly reduced: 20 +/- 3 picomoles/ thyroid. Thyroids of the T3-treated mice responded normally to 1 mM DBcAMP in vitro. From these results it was concluded that the impaired responsiveness of the thyroids to TSH occurs at a step prior to cAMP accumulation.", "contents": "Inhibition of the response of mouse thyroid to tryrotropin induced by chronic triiodothyronine treatment. Administration of 1 mU bovine TSH iv to mice resulted, within 1 hour, in the increase of the serum T4 level from 32 +/- 1.4 ng/ml to 53 +/- 2.6 ng/ml (Mean +/- SE, n = 24). Treatment with 1 mug triiodothyronine (T3) per day, for 10 days, abolished the responsiveness of the thyroid to TSH, as measured by thyroxine (T4) release. Thyroidal response to TSH was measured also in vitro. The basal hormonal release was 4.66 +/- 0.55 ng T4 and 0.98 +/- 0.15 ng T3 per thyroid per 3 h (n = 30). In the presence of bovine TSH (0.2 mU/ml) the hormonal secretion increased 3-fold for T4 and 2.5-fold for T3. Thyroids from mice pretreated with T3 for 10 days showed almost no response to TSH. Partial refractoriness to TSH was already significant 5 days after T3 pretreatment. Responsiveness to TSH was restored 3 days after T3 withdrawal or after 3 daily injections of 10 mU bovine TSH, concomitant with the last 3 days of T3 pretreatment. These results indicated that the prolonged absence of an adequate level of trophic hormone may be the cause of thyroidal unresponsiveness to acute TSH treatment. With 20 mU of TSH, cAMP levels rose from 4 +/- 0.5 picomoles to 80 +/- 9.3 picomoles per thyroid (n = 6). In mice subjected to 10 days of T3 pretreatment the response was markedly reduced: 20 +/- 3 picomoles/ thyroid. Thyroids of the T3-treated mice responded normally to 1 mM DBcAMP in vitro. From these results it was concluded that the impaired responsiveness of the thyroids to TSH occurs at a step prior to cAMP accumulation."} {"id": "PMID:171150", "title": "Effect of estrogen-progestogen administration on tissue cation concentrations in the rat.", "content": "Five studies are reported which were designed to define the effects of an estrogen and a progestogen, alone and in combination, on tissue concentrations (heart, kidney, and liver) of two trace metals (zinc, copper) and four bulk cations (sodium, potassium, calcium, magnesium). Male rats received Premarin (0.08 mg) and/or progesterone (2 mg) in saline intramuscularly 5 days a week for 12 weeks. A significant increase in kidney copper concentrations was the most striking finding in treated, compared to control, animals. A small but significant increase in kidney zinc concentrations also was observed. The changes in cation concentrations in the liver were less striking and consistent, and no changes were observed in cation concentrations of heart muscle. The increase in renal copper was greater with estrogen than with progestogen alone but the two in combination produced an additive effect. Dose-response and time-response changes were documented. Two weeks after discontinuing treatment, renal copper and zinc concentrations returned to control levels.", "contents": "Effect of estrogen-progestogen administration on tissue cation concentrations in the rat. Five studies are reported which were designed to define the effects of an estrogen and a progestogen, alone and in combination, on tissue concentrations (heart, kidney, and liver) of two trace metals (zinc, copper) and four bulk cations (sodium, potassium, calcium, magnesium). Male rats received Premarin (0.08 mg) and/or progesterone (2 mg) in saline intramuscularly 5 days a week for 12 weeks. A significant increase in kidney copper concentrations was the most striking finding in treated, compared to control, animals. A small but significant increase in kidney zinc concentrations also was observed. The changes in cation concentrations in the liver were less striking and consistent, and no changes were observed in cation concentrations of heart muscle. The increase in renal copper was greater with estrogen than with progestogen alone but the two in combination produced an additive effect. Dose-response and time-response changes were documented. Two weeks after discontinuing treatment, renal copper and zinc concentrations returned to control levels."} {"id": "PMID:171151", "title": "Calcium transport in isolated bone cells. III. Effects of parathyroid hormone and cyclic 3',5'-AMP.", "content": "The effects of parathyroid hormone (PTH) and cyclic 3',5'-AMP (cyclic AMP) on calcium transport were studied in isolated bone cells. Bone cells were isolated by collagenase digestion of 20-21 day old fetal rat calvaria. Calcium transport was measured with 45Ca. PTH (0.2 mug/ml) increased calcium uptake 30--40% over control values at 37 C. At 4 C, the effects were magnified and 70--170% increases in calcium uptake were observed. The effects were present 1--10 minutes after the simultaneous addition of hormone and 45Ca. PTH had no effect on calcium efflux. Neither dibutyryl cyclic AMP (10(-4)-10(-3)M) nor cyclic AMP (10(-7)-3 X 10(-6)M) had any effect on calcium uptake or efflux. Methylisobutylxanthine (0.1 mM) caused no change in calcium uptake although increase in cyclic AMP were noted. The characteristic PTH-induced increase in cyclic AMP seen at 37 C was not observed at 4 C. It is postulated that PTH increases the permeability of bone cell membranes to calcium. At 4 C the membrane is relatively impermeable so the PTH effect is magnified. The PTH-induced increase does not appear to be mediated through cyclic AMP.", "contents": "Calcium transport in isolated bone cells. III. Effects of parathyroid hormone and cyclic 3',5'-AMP. The effects of parathyroid hormone (PTH) and cyclic 3',5'-AMP (cyclic AMP) on calcium transport were studied in isolated bone cells. Bone cells were isolated by collagenase digestion of 20-21 day old fetal rat calvaria. Calcium transport was measured with 45Ca. PTH (0.2 mug/ml) increased calcium uptake 30--40% over control values at 37 C. At 4 C, the effects were magnified and 70--170% increases in calcium uptake were observed. The effects were present 1--10 minutes after the simultaneous addition of hormone and 45Ca. PTH had no effect on calcium efflux. Neither dibutyryl cyclic AMP (10(-4)-10(-3)M) nor cyclic AMP (10(-7)-3 X 10(-6)M) had any effect on calcium uptake or efflux. Methylisobutylxanthine (0.1 mM) caused no change in calcium uptake although increase in cyclic AMP were noted. The characteristic PTH-induced increase in cyclic AMP seen at 37 C was not observed at 4 C. It is postulated that PTH increases the permeability of bone cell membranes to calcium. At 4 C the membrane is relatively impermeable so the PTH effect is magnified. The PTH-induced increase does not appear to be mediated through cyclic AMP."} {"id": "PMID:171152", "title": "Effects of parathyroid hormone on the accumulation of cyclic AMP in bone of vitamin D-deficient rats.", "content": "The mechanism of skeletal refractoriness to parathyroid hormone (PTH) in vitamine D-deficient animals was studied in terms of the adenylate cyclase-cyclic AMP system in rat calvaria. In vitamin D-deficient, thyroparathyroidectomized rats, plasma calcium concentration was not elevated by iv administration of PTH, while responsiveness to the hormone was recovered within 24 h after a single dose (2.5 mug) of vitamin D3. In spite of the remarkable dependency of PTH on vitamin D for mobilization of calcium from bone, PTH stimulated adenylate cyclase activity in particulate bone cell fractions in vitro. PTH also enhanced the levels of cyclic AMP in the skeletal tissues of vitamin D-deficient rats in vivo and in vitro to an extent similar to those found in rats given 2.5 mug of D3. Administration of theophylline or dibutyryl cyclic AMP to the vitamin D-deficient rats did not cause any significant hypercalcemic effects, while these drugs enhanced plasma calcium concentration significantly in the rats given vitamin D3. These data strongly indicate that the cause of the skeletal refractoriness to PTH in vitamin D-deficient animals is not a defective activation of adenylate cyclase, but must be related to a later step or steps in the biochemical events leading to bone cell activation.", "contents": "Effects of parathyroid hormone on the accumulation of cyclic AMP in bone of vitamin D-deficient rats. The mechanism of skeletal refractoriness to parathyroid hormone (PTH) in vitamine D-deficient animals was studied in terms of the adenylate cyclase-cyclic AMP system in rat calvaria. In vitamin D-deficient, thyroparathyroidectomized rats, plasma calcium concentration was not elevated by iv administration of PTH, while responsiveness to the hormone was recovered within 24 h after a single dose (2.5 mug) of vitamin D3. In spite of the remarkable dependency of PTH on vitamin D for mobilization of calcium from bone, PTH stimulated adenylate cyclase activity in particulate bone cell fractions in vitro. PTH also enhanced the levels of cyclic AMP in the skeletal tissues of vitamin D-deficient rats in vivo and in vitro to an extent similar to those found in rats given 2.5 mug of D3. Administration of theophylline or dibutyryl cyclic AMP to the vitamin D-deficient rats did not cause any significant hypercalcemic effects, while these drugs enhanced plasma calcium concentration significantly in the rats given vitamin D3. These data strongly indicate that the cause of the skeletal refractoriness to PTH in vitamin D-deficient animals is not a defective activation of adenylate cyclase, but must be related to a later step or steps in the biochemical events leading to bone cell activation."} {"id": "PMID:171153", "title": "Characterization of mouse ACTH in plasma and in extracts of pituitary and of adrenotropic pituitary tumor.", "content": "The predominant component of immunoreactive ACTH in the plasma of adrenalectomized normal mice and of mice bearing the adrenotropic mouse pituitary tumor, AtT-20, and in extracts of the normal mouse pituitary and pituitary tumor, has an elution volume on Sephadex G-50 gel filtration approximately midway between the void volume and the elution volume of human ACTH (1-39 peptide). The tumor extracts are shown to contain, in addition to this intermediate ACTH, 2 other components of immunoreactive ACTH, one which coelutes with 131I-labeled albumin (big ACTH) and the other with [125I]hACTH (little ACTH). Big and intermediate ACTH are urea-stable. Controlled tryptic digestion of mouse-tumor big ACTH results within 10 seconds in conversion to an intermediate component followed by continued loss of immunoreactivity. Under the same conditions of tryptic digestion of intermediate ACTH, there is only continuous loss of immuno-reactivity with no change of hormonal form. These findings strengthen the hypothesis that mouse intermediate ACTH is not a precursor for little ACTH.", "contents": "Characterization of mouse ACTH in plasma and in extracts of pituitary and of adrenotropic pituitary tumor. The predominant component of immunoreactive ACTH in the plasma of adrenalectomized normal mice and of mice bearing the adrenotropic mouse pituitary tumor, AtT-20, and in extracts of the normal mouse pituitary and pituitary tumor, has an elution volume on Sephadex G-50 gel filtration approximately midway between the void volume and the elution volume of human ACTH (1-39 peptide). The tumor extracts are shown to contain, in addition to this intermediate ACTH, 2 other components of immunoreactive ACTH, one which coelutes with 131I-labeled albumin (big ACTH) and the other with [125I]hACTH (little ACTH). Big and intermediate ACTH are urea-stable. Controlled tryptic digestion of mouse-tumor big ACTH results within 10 seconds in conversion to an intermediate component followed by continued loss of immunoreactivity. Under the same conditions of tryptic digestion of intermediate ACTH, there is only continuous loss of immuno-reactivity with no change of hormonal form. These findings strengthen the hypothesis that mouse intermediate ACTH is not a precursor for little ACTH."} {"id": "PMID:171154", "title": "Epileptogenic effects of several penicillins and penicillin-related compounds in rat neocortex.", "content": "Several penicillins and penicillin-related compounds were tested for their ability to produce epileptiform activity in rat neocortex. (1) Alterations in the side chain of penicillin G decreased epileptogenic capability in all the compounds tested in this study: Phenoxymethylpenicillin produced a primary focus but no mirror focus, suggesting a dissociation of the mechanisms underlying these two processes. Ampicillin, 6-aminopenicillanic acid, and potassium 6-aminopenicillanic acid, and potassium 6-aminopenicillanic acid produced little or no epileptiform activity. All these compounds have free amino grounds and are amphoteric. (2) Breaking the beta lactam ring of penicillin G (potassium penicillin G penicilloate) eliminated epileptogenic capability. (3) Potassium salts of penicillin or its derivatives (potassium penicillin G, propicillin, potassium 6-aminopenicillanic acid, potassium penicillin G penicilloate) consistently suppressed cortical activity, regardless of the ability of the compound to produce spike discharges. Thus, mechanisms underlying these two properties can be dissociated. (4) Antibiotic activity of penicillins bears no relationship to epileptogenic capability.", "contents": "Epileptogenic effects of several penicillins and penicillin-related compounds in rat neocortex. Several penicillins and penicillin-related compounds were tested for their ability to produce epileptiform activity in rat neocortex. (1) Alterations in the side chain of penicillin G decreased epileptogenic capability in all the compounds tested in this study: Phenoxymethylpenicillin produced a primary focus but no mirror focus, suggesting a dissociation of the mechanisms underlying these two processes. Ampicillin, 6-aminopenicillanic acid, and potassium 6-aminopenicillanic acid, and potassium 6-aminopenicillanic acid produced little or no epileptiform activity. All these compounds have free amino grounds and are amphoteric. (2) Breaking the beta lactam ring of penicillin G (potassium penicillin G penicilloate) eliminated epileptogenic capability. (3) Potassium salts of penicillin or its derivatives (potassium penicillin G, propicillin, potassium 6-aminopenicillanic acid, potassium penicillin G penicilloate) consistently suppressed cortical activity, regardless of the ability of the compound to produce spike discharges. Thus, mechanisms underlying these two properties can be dissociated. (4) Antibiotic activity of penicillins bears no relationship to epileptogenic capability."} {"id": "PMID:171155", "title": "Adenosine-3':5'-monophosphate-dependent and plasma-membrane-associated protein kinase from bovine corpus luteum. Solubilization and properties of solubilized enzyme.", "content": "The solubilization of plasma membrane fractions FI and FII associated protein kinases has been attempted using monovalent salts of high ionic strength and various detergent treatments. Extraction of FI and FII plasma membranes with high ionic strength salt solutions did not release more than 20% of the protein kinase activity. Similarly, monovalent salts released little adenosine 3':5'-monophosphate (cyclic AMP) binding activity, but after extraction binding capacity of cyclic [3H]AMP to plasma membranes was increased about 150-200%. Triton X-100 was a better solubilizing agent that Lubrol WX or deoxycholate. In addition to solubilization, 0.1% Triton X-100 also stimulated the protein kinase activity 150-200%. The properties of Triton X-100 solubilized FI and FII and purified cytosol KII were characterized with respect to protein substrate specificity, effect of cyclic AMP, cyclic nucleotide specificity, effects of divalent metal ion and gonadotropins. Upon sucrose density gradient centrifugation, FI solubilized protein kinase and cyclic AMP binding activities co-sedimented with a sedimentation coefficient of 6.3 S. The FII solubilized protein kinase sedimented as two components with sedimentation coefficients of 7.7 S and 5.5 S. The cyclic AMP binding activity also sedimented as two components with sedimentation coefficient 6.7 S and 5.5 S. Cyclic AMP caused dissociation of solubilized protein kinase from FI into a single catalytic (4.8 S) and two cyclic AMP binding subunits (8.1 S and 6.7 S). FII solubilized enzyme was dissociated into one catalytic (4.8 S) and one cyclic AMP binding subunit (6.3 S). Fractionation of FI and FII solubilized enzymes on DEAE-cellulose column chromatography resolved them each into two peaks Ia, Ib and IIa, IIb, respectively. Peaks Ib and IIb were more sensitive to cyclic AMP STIMULATION THAN Ia and IIa peaks. From these studies it is concluded that the plasma-membrane associated and cytosol protein kinases have similar catalytic properties but differ in some of their physical properties.", "contents": "Adenosine-3':5'-monophosphate-dependent and plasma-membrane-associated protein kinase from bovine corpus luteum. Solubilization and properties of solubilized enzyme. The solubilization of plasma membrane fractions FI and FII associated protein kinases has been attempted using monovalent salts of high ionic strength and various detergent treatments. Extraction of FI and FII plasma membranes with high ionic strength salt solutions did not release more than 20% of the protein kinase activity. Similarly, monovalent salts released little adenosine 3':5'-monophosphate (cyclic AMP) binding activity, but after extraction binding capacity of cyclic [3H]AMP to plasma membranes was increased about 150-200%. Triton X-100 was a better solubilizing agent that Lubrol WX or deoxycholate. In addition to solubilization, 0.1% Triton X-100 also stimulated the protein kinase activity 150-200%. The properties of Triton X-100 solubilized FI and FII and purified cytosol KII were characterized with respect to protein substrate specificity, effect of cyclic AMP, cyclic nucleotide specificity, effects of divalent metal ion and gonadotropins. Upon sucrose density gradient centrifugation, FI solubilized protein kinase and cyclic AMP binding activities co-sedimented with a sedimentation coefficient of 6.3 S. The FII solubilized protein kinase sedimented as two components with sedimentation coefficients of 7.7 S and 5.5 S. The cyclic AMP binding activity also sedimented as two components with sedimentation coefficient 6.7 S and 5.5 S. Cyclic AMP caused dissociation of solubilized protein kinase from FI into a single catalytic (4.8 S) and two cyclic AMP binding subunits (8.1 S and 6.7 S). FII solubilized enzyme was dissociated into one catalytic (4.8 S) and one cyclic AMP binding subunit (6.3 S). Fractionation of FI and FII solubilized enzymes on DEAE-cellulose column chromatography resolved them each into two peaks Ia, Ib and IIa, IIb, respectively. Peaks Ib and IIb were more sensitive to cyclic AMP STIMULATION THAN Ia and IIa peaks. From these studies it is concluded that the plasma-membrane associated and cytosol protein kinases have similar catalytic properties but differ in some of their physical properties."} {"id": "PMID:171156", "title": "Structure and synthesis of a lipid-containing bacteriophage. Chemical modifications of bacteriophage PM2 and the resulting alterations in acyl-chain motion in the PM2 membrane.", "content": "The nucleocapsid proteins of bacteriophage PM2 and the inner lamella of the lipid bilayer, containing most of the phosphatidlethanolamine residues, were selectively cross-linked in the presence of 0.1-0.5% glutaraldehyde, 5 mM dimethylsuberimidate, or 0.05% toluene 2,4-diisocyanate. The biological activity (p.f.u.) of PM2 modified by these reagents decreased 10(6)-fold in all cases. The spike and coat proteins were selectively cross-linked in the presence of 7.5 mM N,N'-p-phenylenedimaleimide. The biological activity of virus modified by this reagen was unaffected. The electron paramagnetic resonance spectra of fatty acid spin labels incorporated into native and chemically modified viral membranes were qualitatively similar but show quantitative differences. Fixation with glutaraldehyde increased the rigidity of the membrane while Triton X-100 induced a more flexible structure. There was no change in the electron paramagnetic resonance spectrum of virus treated with N,N'-p-phenylenedimaleimide, however.", "contents": "Structure and synthesis of a lipid-containing bacteriophage. Chemical modifications of bacteriophage PM2 and the resulting alterations in acyl-chain motion in the PM2 membrane. The nucleocapsid proteins of bacteriophage PM2 and the inner lamella of the lipid bilayer, containing most of the phosphatidlethanolamine residues, were selectively cross-linked in the presence of 0.1-0.5% glutaraldehyde, 5 mM dimethylsuberimidate, or 0.05% toluene 2,4-diisocyanate. The biological activity (p.f.u.) of PM2 modified by these reagents decreased 10(6)-fold in all cases. The spike and coat proteins were selectively cross-linked in the presence of 7.5 mM N,N'-p-phenylenedimaleimide. The biological activity of virus modified by this reagen was unaffected. The electron paramagnetic resonance spectra of fatty acid spin labels incorporated into native and chemically modified viral membranes were qualitatively similar but show quantitative differences. Fixation with glutaraldehyde increased the rigidity of the membrane while Triton X-100 induced a more flexible structure. There was no change in the electron paramagnetic resonance spectrum of virus treated with N,N'-p-phenylenedimaleimide, however."} {"id": "PMID:171157", "title": "Replication of colicinogenic factor E1 DNA in plasmolysed Escherichia coli cells. Coupling of DNA replication and RNA synthesis.", "content": "Plasmolysed chloramphenicol-treated Escherichia coli cells carrying the colicinogenic factor E1 utilize deoxynucleoside triphosphates for the semi-conservative synthesis of Col E1 DNA. Col E1 DNA replication in plasmolysed cells can be dissociated into two temporally separated processes: (a) a rifampicin-sensitive RNA synthesis, which is stimulated by adenosine 3':5'-monophosphate (cyclic AMP) and requires all four ribonucleoside triphosphates and (b) an ATP-dependent DNA synthesis, which is inhibited by arabinosylnucleoside triphosphates and sulfhydryl-blocking reagents. Thes two processes exhibit different sensitivities to inhibition by polyamines and actinomycin D.", "contents": "Replication of colicinogenic factor E1 DNA in plasmolysed Escherichia coli cells. Coupling of DNA replication and RNA synthesis. Plasmolysed chloramphenicol-treated Escherichia coli cells carrying the colicinogenic factor E1 utilize deoxynucleoside triphosphates for the semi-conservative synthesis of Col E1 DNA. Col E1 DNA replication in plasmolysed cells can be dissociated into two temporally separated processes: (a) a rifampicin-sensitive RNA synthesis, which is stimulated by adenosine 3':5'-monophosphate (cyclic AMP) and requires all four ribonucleoside triphosphates and (b) an ATP-dependent DNA synthesis, which is inhibited by arabinosylnucleoside triphosphates and sulfhydryl-blocking reagents. Thes two processes exhibit different sensitivities to inhibition by polyamines and actinomycin D."} {"id": "PMID:171158", "title": "The influence of insulin on glucose permeability and metabolism of human granulocytes.", "content": "Viable human polymorphonuclear leukocytes isolated from peripheral blood were incubated for 1 h at 37 degrees C with variable concentrations of insulin in a saline medium buffered at pH 7.4. The hormone increased glucose consumption by about 40% without influencing the permeability of the membranes to glucose, whose uptake followed a passive diffusion process. The measurement of intermediates localized activation of glycolysis by insulin, down to 0.36 nM, at the phosphofructokinase step. However, the spectrophotometric measurement showed no activation of phosphofructokinase after preincubation with insulin of either intact granulocytes or crude or ultracentrifuged homogenates. The level of cyclic AMP, which is known to activate phosphofructokinase, was not modified by insulin; cyclic GMP did not activate the enzyme in the granulocyte extracts: neither of the two nucleotides can therefore be considered as a direct messenger of the action of insulin on phosphofructokinase. An important fraction of the extra glucose consumed under the influence of insulin was recovered as neither glycogen nor lactate, nor was it oxidized in the Krebs cycle. It might be assumed to have been converted into glycerolipids. However, insulin produced no detectable accumulation of triglycerides and activated neither the pentose phosphate pathway nor oxidative decarboxylation of pyruvate. The fate of the extra glucose consumed under the influence of insulin therefore remains questionable.", "contents": "The influence of insulin on glucose permeability and metabolism of human granulocytes. Viable human polymorphonuclear leukocytes isolated from peripheral blood were incubated for 1 h at 37 degrees C with variable concentrations of insulin in a saline medium buffered at pH 7.4. The hormone increased glucose consumption by about 40% without influencing the permeability of the membranes to glucose, whose uptake followed a passive diffusion process. The measurement of intermediates localized activation of glycolysis by insulin, down to 0.36 nM, at the phosphofructokinase step. However, the spectrophotometric measurement showed no activation of phosphofructokinase after preincubation with insulin of either intact granulocytes or crude or ultracentrifuged homogenates. The level of cyclic AMP, which is known to activate phosphofructokinase, was not modified by insulin; cyclic GMP did not activate the enzyme in the granulocyte extracts: neither of the two nucleotides can therefore be considered as a direct messenger of the action of insulin on phosphofructokinase. An important fraction of the extra glucose consumed under the influence of insulin was recovered as neither glycogen nor lactate, nor was it oxidized in the Krebs cycle. It might be assumed to have been converted into glycerolipids. However, insulin produced no detectable accumulation of triglycerides and activated neither the pentose phosphate pathway nor oxidative decarboxylation of pyruvate. The fate of the extra glucose consumed under the influence of insulin therefore remains questionable."} {"id": "PMID:171159", "title": "Sites of action of fusidic acid in eukaryotes. Inhibition by fusidic acid of a ribosome-independent GTPase from Artemia salina embryos.", "content": "1. A ribosome-independent GTPase activity has been isolated from the high-speed supernatant fraction of Artemia salina embryos, and some of its properties have been studied. This activity is inhibited by fusidic acid, an antibiotic generally thought to inhibit only EF-2 in eukaryotes. However, several lines of evidence indicate that the GTPase activity, described here, is distinct from EF-2. The results suggest, therefore, that the inhibitory effect of fusidic acid in eukaryotic systems is not restricted to EF-2 (and ribosome)-dependent functions only. 2. The results of other experiments have revealed that, despite its ability to inhibit the GTPase activity mentioned above, fusidic acid is not a non-specific inhibitor of all ribosome-independent GTPase and ATPase activities present in eukaryotic cells.", "contents": "Sites of action of fusidic acid in eukaryotes. Inhibition by fusidic acid of a ribosome-independent GTPase from Artemia salina embryos. 1. A ribosome-independent GTPase activity has been isolated from the high-speed supernatant fraction of Artemia salina embryos, and some of its properties have been studied. This activity is inhibited by fusidic acid, an antibiotic generally thought to inhibit only EF-2 in eukaryotes. However, several lines of evidence indicate that the GTPase activity, described here, is distinct from EF-2. The results suggest, therefore, that the inhibitory effect of fusidic acid in eukaryotic systems is not restricted to EF-2 (and ribosome)-dependent functions only. 2. The results of other experiments have revealed that, despite its ability to inhibit the GTPase activity mentioned above, fusidic acid is not a non-specific inhibitor of all ribosome-independent GTPase and ATPase activities present in eukaryotic cells."} {"id": "PMID:171160", "title": "The allosteric properties of beef-liver fructose bisphosphatase.", "content": "1. The activity of beef liver fructose bisphosphatase has been shown to respond cooperatively to increasing concentrations of the activating cations Mg2+ and Mn2+. The allosteric inhibitor AMP caused an increase in this cooperativity and a decrease in the apparent affinity of the enzyme for the activating cation. 2. The cooperative response of the enzyme to AMP is similarly increased by increasing cation concentrations with a concomitant decrease in the apparent affinity. 3. Direct binding experiments indicated that in the absence of either Mg2+ or Mn2+ the enzyme bound AMP non-cooperatively up to a maximum of two molecules per molecule of enzyme, a result that is indicative of half-sites reactivity. The binding became increasingly cooperative as the concentration of the activating cation was increased. 4. The substrate fructose bisphosphate had no effect on any of these cooperative responses. 5. These results may be most simply interpreted in terms of concerted model in which the activating cation functions both as an allosteric activator and as an essential cofactor for the reaction.", "contents": "The allosteric properties of beef-liver fructose bisphosphatase. 1. The activity of beef liver fructose bisphosphatase has been shown to respond cooperatively to increasing concentrations of the activating cations Mg2+ and Mn2+. The allosteric inhibitor AMP caused an increase in this cooperativity and a decrease in the apparent affinity of the enzyme for the activating cation. 2. The cooperative response of the enzyme to AMP is similarly increased by increasing cation concentrations with a concomitant decrease in the apparent affinity. 3. Direct binding experiments indicated that in the absence of either Mg2+ or Mn2+ the enzyme bound AMP non-cooperatively up to a maximum of two molecules per molecule of enzyme, a result that is indicative of half-sites reactivity. The binding became increasingly cooperative as the concentration of the activating cation was increased. 4. The substrate fructose bisphosphate had no effect on any of these cooperative responses. 5. These results may be most simply interpreted in terms of concerted model in which the activating cation functions both as an allosteric activator and as an essential cofactor for the reaction."} {"id": "PMID:171161", "title": "Contrasting effects on plasma lipoproteins of intravenous versus oral administration of a triglyceride-phospholipid emulsion.", "content": "The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5-6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride-egg yolk phospholipid emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1.006-1.063 fraction of plasma. In vitro studies showed that exchange readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism.", "contents": "Contrasting effects on plasma lipoproteins of intravenous versus oral administration of a triglyceride-phospholipid emulsion. The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5-6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride-egg yolk phospholipid emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1.006-1.063 fraction of plasma. In vitro studies showed that exchange readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism."} {"id": "PMID:171162", "title": "The effect of blocking dopamine release on synthesis rate of dopamine in the striatum of the rat.", "content": "Two experiments were carried out in rats to investigate the mechanisms by which dopamine (DA) synthesis is regulated. First, a unilateral lesion was made in the substantia nigra, thus interrupting the nervous impulse flow of the nigro-striatal pathway. Secondly, the release of DA in the striatum was blocked by means of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966). In both experiments the synthesis rate of DA was accelerated as was shown by analysing the time course of the specific activity of striatal DA after an i.v. injection of 3,5-3H-tyrosine. Furthermore the influence of apomorphine on the rate of DA synthesis, accelerated by HA-966 or by lesion, was investigated. Apomorphine appeared to block the increase of DA synthesis. The results are discussed in the light of a transsynaptic feedback mechanism.", "contents": "The effect of blocking dopamine release on synthesis rate of dopamine in the striatum of the rat. Two experiments were carried out in rats to investigate the mechanisms by which dopamine (DA) synthesis is regulated. First, a unilateral lesion was made in the substantia nigra, thus interrupting the nervous impulse flow of the nigro-striatal pathway. Secondly, the release of DA in the striatum was blocked by means of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966). In both experiments the synthesis rate of DA was accelerated as was shown by analysing the time course of the specific activity of striatal DA after an i.v. injection of 3,5-3H-tyrosine. Furthermore the influence of apomorphine on the rate of DA synthesis, accelerated by HA-966 or by lesion, was investigated. Apomorphine appeared to block the increase of DA synthesis. The results are discussed in the light of a transsynaptic feedback mechanism."} {"id": "PMID:171163", "title": "Tricaine (MS-222): effects on ionic conductances of squid axon membranes.", "content": "Experiments utilizing internally perfused squid giant axons have been carried out to determine the mode of action of tricaine (MS-222) in producing its anesthetic effects. Tricaine, in concentrations of 1 and 3 mM, was applied to the internal surface of the membrane via the perfusion system. Peak sodium current and steady-state potassium current were measured by the axial-wire voltage clamp technique. Tricaine suppressed both of these membrane ionic currents with the major effect being on the peak sodium current. Its action on nerve membrane appeared quite similar to other local anesthetics. One major difference was noted in that tricaine shifts sodium conductance curves in the direction of depolarization along the potential axis, an effect quite similar to that observed with increasing external Ca2+ concentration and with application of pentobarbital.", "contents": "Tricaine (MS-222): effects on ionic conductances of squid axon membranes. Experiments utilizing internally perfused squid giant axons have been carried out to determine the mode of action of tricaine (MS-222) in producing its anesthetic effects. Tricaine, in concentrations of 1 and 3 mM, was applied to the internal surface of the membrane via the perfusion system. Peak sodium current and steady-state potassium current were measured by the axial-wire voltage clamp technique. Tricaine suppressed both of these membrane ionic currents with the major effect being on the peak sodium current. Its action on nerve membrane appeared quite similar to other local anesthetics. One major difference was noted in that tricaine shifts sodium conductance curves in the direction of depolarization along the potential axis, an effect quite similar to that observed with increasing external Ca2+ concentration and with application of pentobarbital."} {"id": "PMID:171167", "title": "Types of neuronal responses in the rat thalamus to peripheral temperature changes.", "content": "Recordings were made of spike-trains from 163 neurons of the rostral part of the ventrobasal thalamus complex of the rat while the temperature of the scrotal skin was altered. The following results were obtained: 55 neurons were non-thermosensitive, 7 neurons cold-sensitive and 101 neurons warm-sensitive. In the case of the warm-sensitive cells a definite discrimination was possible: 61.4% of the neurons altered their firing behavior during peripheral cooling, changing from relatively even spike frequency to burst firing. This change could be induced repeatedly by altering the temperature. 38.6% of the neurons, on the other hand, reacted to cooling by slowing down their frequency. By way of statistical methods the firing patterns of the two response-types were analyzed more precisely and the differences in response to temperature stimuli more exactly defined. Likewise, the spatial distribution of the two response-types of warm-sensitive cells exhibited differences; whereas the cells devoid of burst activity occured rather uniformly in the region of the thalamus studied, the cells with bursting activity were confined more to the mediocaudal region. These findings are discussed with regard to the phenomenon of peripheral bursts and to the projection of thermoafferent pathways onto the ventrobasal thalamus complex. The functional interpretation of the various cell reactions and their role in the central processing of thermoafferent signals still remains unexplained and requires comparative studies of peripheral and central parts of the thermoafferent system.", "contents": "Types of neuronal responses in the rat thalamus to peripheral temperature changes. Recordings were made of spike-trains from 163 neurons of the rostral part of the ventrobasal thalamus complex of the rat while the temperature of the scrotal skin was altered. The following results were obtained: 55 neurons were non-thermosensitive, 7 neurons cold-sensitive and 101 neurons warm-sensitive. In the case of the warm-sensitive cells a definite discrimination was possible: 61.4% of the neurons altered their firing behavior during peripheral cooling, changing from relatively even spike frequency to burst firing. This change could be induced repeatedly by altering the temperature. 38.6% of the neurons, on the other hand, reacted to cooling by slowing down their frequency. By way of statistical methods the firing patterns of the two response-types were analyzed more precisely and the differences in response to temperature stimuli more exactly defined. Likewise, the spatial distribution of the two response-types of warm-sensitive cells exhibited differences; whereas the cells devoid of burst activity occured rather uniformly in the region of the thalamus studied, the cells with bursting activity were confined more to the mediocaudal region. These findings are discussed with regard to the phenomenon of peripheral bursts and to the projection of thermoafferent pathways onto the ventrobasal thalamus complex. The functional interpretation of the various cell reactions and their role in the central processing of thermoafferent signals still remains unexplained and requires comparative studies of peripheral and central parts of the thermoafferent system."} {"id": "PMID:171168", "title": "A direct input from amygdaloid complex to caudate nucleus of the rat.", "content": "Spontaneous unit activity was recorded from the caudate nucleus in rats anesthetized with urethane. Amygdaloid nucleus stimulation altered the spontaneous activity of 51 units (65% of the population tested); 23 units (29%) showed an increase and 28 (36%) a decrease of discharge rate. Moreover, 25 units (32%) responded to stimulation with stimulus-locked spikes. Post-stimulus time histograms revealed 7 patterns of response to amygdaloid stimulation. In 4 groups of cells, stimulus-locked spikes occurred followed by alteration of spontaneous discharge rate. In another 2 groups there was a change of spontaneous discharge without stimulus-locked spikes and in the final group no effect occurred. The possibility of mono-, oligo-, and polysynaptic connections from amygdaloid nuclear complex to caudate nucleus was discussed. It was suggested that an amygdalofugal connection to basal ganglia may provide a pathway whereby activity of the limbic system may exert a modulatory influence on somatic motor mechanisms.", "contents": "A direct input from amygdaloid complex to caudate nucleus of the rat. Spontaneous unit activity was recorded from the caudate nucleus in rats anesthetized with urethane. Amygdaloid nucleus stimulation altered the spontaneous activity of 51 units (65% of the population tested); 23 units (29%) showed an increase and 28 (36%) a decrease of discharge rate. Moreover, 25 units (32%) responded to stimulation with stimulus-locked spikes. Post-stimulus time histograms revealed 7 patterns of response to amygdaloid stimulation. In 4 groups of cells, stimulus-locked spikes occurred followed by alteration of spontaneous discharge rate. In another 2 groups there was a change of spontaneous discharge without stimulus-locked spikes and in the final group no effect occurred. The possibility of mono-, oligo-, and polysynaptic connections from amygdaloid nuclear complex to caudate nucleus was discussed. It was suggested that an amygdalofugal connection to basal ganglia may provide a pathway whereby activity of the limbic system may exert a modulatory influence on somatic motor mechanisms."} {"id": "PMID:171176", "title": "Adrenal function during chronic danazol administration.", "content": "Ten healthy female volunteers received Danazol, 400 mg twice daily for 90 days. Adrenal function testing then showed a normal capacity of the gland to respond to stimulation with synthetic adrenocorticotrophic hormone, and a lack of suppression of central areas controlling adrenal function by a normal response to the metyrapone challenge.", "contents": "Adrenal function during chronic danazol administration. Ten healthy female volunteers received Danazol, 400 mg twice daily for 90 days. Adrenal function testing then showed a normal capacity of the gland to respond to stimulation with synthetic adrenocorticotrophic hormone, and a lack of suppression of central areas controlling adrenal function by a normal response to the metyrapone challenge."} {"id": "PMID:171177", "title": "Contraception and cervical colonization with mycoplasmas and infection with cytomegalovirus.", "content": "The relationship of cervical colonization of genital mycoplasmas and infection with cytomegalovirus (CMV) was studied in 66 intrauterine device (IUD) users as contrasted to 60 patients using oral contraception and 50 patients using neither an IUD nor oral contraception. No significant increase in colonization or genital mycoplasmas or infection with CMV was noted in IUD users. No CMV was isolated from users of the cooper-t IUD. It is unlikely that genital mycoplasmas are related to either the increased immunoglobulin levels seen in patients using the IUD or the antifertility effects of the IUD.", "contents": "Contraception and cervical colonization with mycoplasmas and infection with cytomegalovirus. The relationship of cervical colonization of genital mycoplasmas and infection with cytomegalovirus (CMV) was studied in 66 intrauterine device (IUD) users as contrasted to 60 patients using oral contraception and 50 patients using neither an IUD nor oral contraception. No significant increase in colonization or genital mycoplasmas or infection with CMV was noted in IUD users. No CMV was isolated from users of the cooper-t IUD. It is unlikely that genital mycoplasmas are related to either the increased immunoglobulin levels seen in patients using the IUD or the antifertility effects of the IUD."} {"id": "PMID:171178", "title": "Treatment of RSV-transformed \"poorly\" virogenic and non-virogenic mammalian cell lines with inhibitors of protein synthesis: failure to potentiate RSV rescue.", "content": "Treatment of the RSV-transformed \"poorly\" virogenic rat clones LW13-RsK4 and LW13-RsK4 R1 with cycloheximide or puromycin before fusion with chick embryo fibroblasts did not lead to RSV rescue. Neither was RSV rescued from the RSV-transformed non-virogenic mouse line RVP3 treated with 5-bromodeoxyuridine and cycloheximide or puromycin before fusion.", "contents": "Treatment of RSV-transformed \"poorly\" virogenic and non-virogenic mammalian cell lines with inhibitors of protein synthesis: failure to potentiate RSV rescue. Treatment of the RSV-transformed \"poorly\" virogenic rat clones LW13-RsK4 and LW13-RsK4 R1 with cycloheximide or puromycin before fusion with chick embryo fibroblasts did not lead to RSV rescue. Neither was RSV rescued from the RSV-transformed non-virogenic mouse line RVP3 treated with 5-bromodeoxyuridine and cycloheximide or puromycin before fusion."} {"id": "PMID:171179", "title": "[The relations between lactation and cyclic-AMP -- The influences of adenyl cyclase activity on casein biosynthesis ability in the organ culture of the mouse mammary gland (author's transl)].", "content": "The relationships between hormonal action and cyclic AMP as the second messenger of hormones have recently been discussed on many hormones. Lactation is influenced by various hormone, especially, insulin, prolactin, and hydrocortisone. Whether adenyl cyclase activity in the mammary gland of mouse epithelial cells has parallel relations with casein biosynthesis ability or not was examined using the mammary gland organ culture method. Female, mid-pregnant (11-14 days), mice of DDY strain were used. Organ culture was done by the Chen's floating lens' paper method, using the hormone-added MEM media and non-added ones. Casein biosynthesis ability was measured by observing 32P incorporation into the casein molecules. Adenyl cyclase activity was estimated by the amount of 14-C-cyclic AMP produced out of adenine-8-14C by the Kuo and Krishna's method. Radio isotope compounds were pulsed for 4 hours in the medium. The experiments revealed that the added hormones had a remarkable effect on caein biosynthesis ability, but none on adenyl cyclase activity. No parallel fluctuation was observed between adenyl cyclase activity and casein biosynthesis ability, that is, the change of adenyl cyclase activity was found to have nothing to do with casein biosynthesis ability. Consequently, the cyclic AMP addition to the media showed no effect on casein biosynthesis ability.", "contents": "[The relations between lactation and cyclic-AMP -- The influences of adenyl cyclase activity on casein biosynthesis ability in the organ culture of the mouse mammary gland (author's transl)]. The relationships between hormonal action and cyclic AMP as the second messenger of hormones have recently been discussed on many hormones. Lactation is influenced by various hormone, especially, insulin, prolactin, and hydrocortisone. Whether adenyl cyclase activity in the mammary gland of mouse epithelial cells has parallel relations with casein biosynthesis ability or not was examined using the mammary gland organ culture method. Female, mid-pregnant (11-14 days), mice of DDY strain were used. Organ culture was done by the Chen's floating lens' paper method, using the hormone-added MEM media and non-added ones. Casein biosynthesis ability was measured by observing 32P incorporation into the casein molecules. Adenyl cyclase activity was estimated by the amount of 14-C-cyclic AMP produced out of adenine-8-14C by the Kuo and Krishna's method. Radio isotope compounds were pulsed for 4 hours in the medium. The experiments revealed that the added hormones had a remarkable effect on caein biosynthesis ability, but none on adenyl cyclase activity. No parallel fluctuation was observed between adenyl cyclase activity and casein biosynthesis ability, that is, the change of adenyl cyclase activity was found to have nothing to do with casein biosynthesis ability. Consequently, the cyclic AMP addition to the media showed no effect on casein biosynthesis ability."} {"id": "PMID:171183", "title": "The influence of hemolymph-binding protein on juvenile hormone stability and distribution in Manduca sexta fat body and imaginal discs in vitro.", "content": "The wing discs and fat body of Manduca sexta larvae contain enzymes (i.e. carboxylesterase and epoxide hydratase) that can convert the C18 juvenile hormone (JH) to the acid, diol and acid diol. No evidence of oxidative degradation was noted. In vitro studies suggest that JH can be compartmentalized within the cells of the fat body where it is less accessible to degradative mechanisms. Experiments utilizing a hemolymph-binding protein fraction (BPF) in vitro with fat body and imaginal discs indicate that the BPF retards the uptake of JH by tissues and its subsequent degradation by tissue enzymes. BPF also appears to protect JH from degradation by enzymes released into the medium. By these mechanisms the insect can maintain elevated JH titers for relatively long periods. Binding protein may also keep JH in solution in the hemolymph allowing its rapid distribution throughout the insect. The data suggest that the binding protein plays a key role in maintaining juvenile hormone titers.", "contents": "The influence of hemolymph-binding protein on juvenile hormone stability and distribution in Manduca sexta fat body and imaginal discs in vitro. The wing discs and fat body of Manduca sexta larvae contain enzymes (i.e. carboxylesterase and epoxide hydratase) that can convert the C18 juvenile hormone (JH) to the acid, diol and acid diol. No evidence of oxidative degradation was noted. In vitro studies suggest that JH can be compartmentalized within the cells of the fat body where it is less accessible to degradative mechanisms. Experiments utilizing a hemolymph-binding protein fraction (BPF) in vitro with fat body and imaginal discs indicate that the BPF retards the uptake of JH by tissues and its subsequent degradation by tissue enzymes. BPF also appears to protect JH from degradation by enzymes released into the medium. By these mechanisms the insect can maintain elevated JH titers for relatively long periods. Binding protein may also keep JH in solution in the hemolymph allowing its rapid distribution throughout the insect. The data suggest that the binding protein plays a key role in maintaining juvenile hormone titers."} {"id": "PMID:171184", "title": "Changes in 5alpha- dihydrotestosterone binding to epididymal cytosol during sexual maturation in rabbits: correlation with morphological changes in the testis and epididymis.", "content": "We previously demonstrated that the caput epididymis of intact sexually mature rabbits contains a specific high-affinity binding protein for 5alpha-dihydrotestosterone (5alphaDHT). The other anatomical segments (corpus and cauda) of the epididymes of these animals had no detectable 5alphaDHT-binding activity. We have further shown that this binding was due to an androgen-binding protein of testicular origin. In the present study we have investigated 5alphaDHT binding to epididymal cytosol from sexually immature rabbits (20-104 days old). Using sucrose gradient ultracentrifugation, we have detected a unique pattern of binding. The pattern correlated well with testicular and epididymal maturation, but there was little correlation with chronological age or body weight. In the most immature animals (Group I) the seminiferous tubules appeared as solid cords and the epithelium of the ductus epididymis detectable 5alphaDHT-binding activity. In the second group (Group II), there was 5alphaDHT-binding to all three segments. The seminiferous tubules of these rabbits exhibited spermatogenic activity and lumen formation. The height of the epididymal epithelium had increased uniformly throughout the duct. The third group (Group III) had 5alphaDHT-binding only in caput cytosol. Spermatogenesis had progressed to the formation of elongated spermatids in the most immature animals of this group to the release of spermatozoa in the most mature ones. The caput epithelium of this last group of rabbits was fully differentiated. Unilateral orchidectomy of Group II rabbits resulted in a decrease in [3H]5alphaDHT-binding activity on the operated side as compared to the contralateral non-operated control side, suggesting the testicular origin of the binding protein. The failure of cyproterone or cyproterone acetate to inhibit [3H]5alphaDHT-binding to the protein, the lack of effect of N-ethylmaleimide on binding, and the rapid dissociation rate of the [3H]5alphaDHT-binding protein complex suggested that the binding moiety was testicular androgen-binding protein (ABP).", "contents": "Changes in 5alpha- dihydrotestosterone binding to epididymal cytosol during sexual maturation in rabbits: correlation with morphological changes in the testis and epididymis. We previously demonstrated that the caput epididymis of intact sexually mature rabbits contains a specific high-affinity binding protein for 5alpha-dihydrotestosterone (5alphaDHT). The other anatomical segments (corpus and cauda) of the epididymes of these animals had no detectable 5alphaDHT-binding activity. We have further shown that this binding was due to an androgen-binding protein of testicular origin. In the present study we have investigated 5alphaDHT binding to epididymal cytosol from sexually immature rabbits (20-104 days old). Using sucrose gradient ultracentrifugation, we have detected a unique pattern of binding. The pattern correlated well with testicular and epididymal maturation, but there was little correlation with chronological age or body weight. In the most immature animals (Group I) the seminiferous tubules appeared as solid cords and the epithelium of the ductus epididymis detectable 5alphaDHT-binding activity. In the second group (Group II), there was 5alphaDHT-binding to all three segments. The seminiferous tubules of these rabbits exhibited spermatogenic activity and lumen formation. The height of the epididymal epithelium had increased uniformly throughout the duct. The third group (Group III) had 5alphaDHT-binding only in caput cytosol. Spermatogenesis had progressed to the formation of elongated spermatids in the most immature animals of this group to the release of spermatozoa in the most mature ones. The caput epithelium of this last group of rabbits was fully differentiated. Unilateral orchidectomy of Group II rabbits resulted in a decrease in [3H]5alphaDHT-binding activity on the operated side as compared to the contralateral non-operated control side, suggesting the testicular origin of the binding protein. The failure of cyproterone or cyproterone acetate to inhibit [3H]5alphaDHT-binding to the protein, the lack of effect of N-ethylmaleimide on binding, and the rapid dissociation rate of the [3H]5alphaDHT-binding protein complex suggested that the binding moiety was testicular androgen-binding protein (ABP)."} {"id": "PMID:171185", "title": "Mechanism of action of progesterone on amphibian oocytes. A possible biological role for progesterone metabolism.", "content": "The ability of various steroids to induce maturation of Pleurodeles waltlii oocytes after incubation has been studied. Progesterone is metabolized during the course of maturation. All metabolites isolated are less efficient than progesterone for inducing germinal vesicle breakdown. Progesterone binding to the 'melanosome' fraction has been studied (KD = 4.5 X 10(-8) M at 4 degrees C). 20BETA-Hydroxy-pregn-4-en-3-one, the main progesterone metabolite isolated from the oocyte, also binds to the melanosome fraction, but with a lower affinity (KD = 1.6 X 10(-7) M at 4 degrees C). At high concentration 20beta-hydroxy-pregn-4-en-3-one induces maturation, but at low concentration it is a competitive inhibitor of progesterone. Progesterone metabolism in Pleurodeles oocytes can be interpreted as an inactivation process, and also as a mechanism for inhibitime progesterone action.", "contents": "Mechanism of action of progesterone on amphibian oocytes. A possible biological role for progesterone metabolism. The ability of various steroids to induce maturation of Pleurodeles waltlii oocytes after incubation has been studied. Progesterone is metabolized during the course of maturation. All metabolites isolated are less efficient than progesterone for inducing germinal vesicle breakdown. Progesterone binding to the 'melanosome' fraction has been studied (KD = 4.5 X 10(-8) M at 4 degrees C). 20BETA-Hydroxy-pregn-4-en-3-one, the main progesterone metabolite isolated from the oocyte, also binds to the melanosome fraction, but with a lower affinity (KD = 1.6 X 10(-7) M at 4 degrees C). At high concentration 20beta-hydroxy-pregn-4-en-3-one induces maturation, but at low concentration it is a competitive inhibitor of progesterone. Progesterone metabolism in Pleurodeles oocytes can be interpreted as an inactivation process, and also as a mechanism for inhibitime progesterone action."} {"id": "PMID:171186", "title": "In vivo effect of anti-estrogens on the localisation and replenishment of estrogen receptor.", "content": "Interactions between estrogen recpetors and triaryl ethylene anti-estrogens (U-11100A, MER 25 and CI 628) were tested on immature rat uteri. The accessible and the total (accessible and occupied) estrogen receptor sites were assayed in the cytosol and nuclear extracts using charcoal adsorption. After in vivo administration of anti-estrogens, the estradiol receptor sites were occupied and subsequently transferred to the nuclear compartment. The nuclear localisation of the receptor induced by the antagonist lasted for several days, during which replenishment of the cytosol receptor occurred. The nuclear receptors transferred by anti-estrogens and labelled in vitro with [3H]estradiol, were similar to the nuclear receptor-estradiol complex formed in vivo as far as their sedimentation constants and extractability from nuclei were concerned. Although these anti-estrogens are capable to translocate the estrogen receptor to the nucleus and to induce the replenishment of the cytosol receptor, the mechanism of their antagonism and of their weak estrogenic activity is still not clear.", "contents": "In vivo effect of anti-estrogens on the localisation and replenishment of estrogen receptor. Interactions between estrogen recpetors and triaryl ethylene anti-estrogens (U-11100A, MER 25 and CI 628) were tested on immature rat uteri. The accessible and the total (accessible and occupied) estrogen receptor sites were assayed in the cytosol and nuclear extracts using charcoal adsorption. After in vivo administration of anti-estrogens, the estradiol receptor sites were occupied and subsequently transferred to the nuclear compartment. The nuclear localisation of the receptor induced by the antagonist lasted for several days, during which replenishment of the cytosol receptor occurred. The nuclear receptors transferred by anti-estrogens and labelled in vitro with [3H]estradiol, were similar to the nuclear receptor-estradiol complex formed in vivo as far as their sedimentation constants and extractability from nuclei were concerned. Although these anti-estrogens are capable to translocate the estrogen receptor to the nucleus and to induce the replenishment of the cytosol receptor, the mechanism of their antagonism and of their weak estrogenic activity is still not clear."} {"id": "PMID:171190", "title": "Comparison of alpha- and beta-cell secretory responses in islets isolated with collagenase and in the isolated perfused pancreas of rats.", "content": "The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system. The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic.", "contents": "Comparison of alpha- and beta-cell secretory responses in islets isolated with collagenase and in the isolated perfused pancreas of rats. The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system. The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic."} {"id": "PMID:171191", "title": "Changes of enzyme activities in spleen lymphocytes from tumor-bearing rats.", "content": "The induction of concomitant immunity was studied in Donryu strain rats with Yoshida ascites sarcoma cells. The changes of enzyme activity in spleen lymphocytes were also examined in normal and tumor-bearing rats. The concomitant immunity was detected 1 week after transplantation of tumor cells. Extended metastases were found 2 weeks after transplantation. The enzyme activities of ATPase and acid phosphatase were definitely higher than that of normal rat 1 week after the transplantation but decreased to lower level than normal 2 weeks later. On the other hand, alkaline phosphatase activity increased 3 times at 1 week after the transplantation and remained at the same level even at 2 weeks later.", "contents": "Changes of enzyme activities in spleen lymphocytes from tumor-bearing rats. The induction of concomitant immunity was studied in Donryu strain rats with Yoshida ascites sarcoma cells. The changes of enzyme activity in spleen lymphocytes were also examined in normal and tumor-bearing rats. The concomitant immunity was detected 1 week after transplantation of tumor cells. Extended metastases were found 2 weeks after transplantation. The enzyme activities of ATPase and acid phosphatase were definitely higher than that of normal rat 1 week after the transplantation but decreased to lower level than normal 2 weeks later. On the other hand, alkaline phosphatase activity increased 3 times at 1 week after the transplantation and remained at the same level even at 2 weeks later."} {"id": "PMID:171192", "title": "Mucopolysaccharides of rat ascites hepatoma, AH-100B.", "content": "The present study was undertaken to determine the mucopolysaccharide content of cells, AH-100B, and in the ascites, liver, and kidney of a rat bearing this hepatoma. AH-100B is similar to other mixed-type cells in having heparan sulfate as the main component in its mucopolysaccharides but its minor component was different in containing heparin. The main mucopolysaccharide in the ascites of AH-100B bearing rat was hyaluronic acid, which was similar to that of control ascites induced by injection of polypeptone, but minor component contained heparin derived from the cells. The content of hyaluronic acid in the liver of a rat bearing this hepatoma was higher than those of control liver and liver of a rat bearing other tumors. There were no significant differences between control kidney and kidney of a rat bearing this hepatoma.", "contents": "Mucopolysaccharides of rat ascites hepatoma, AH-100B. The present study was undertaken to determine the mucopolysaccharide content of cells, AH-100B, and in the ascites, liver, and kidney of a rat bearing this hepatoma. AH-100B is similar to other mixed-type cells in having heparan sulfate as the main component in its mucopolysaccharides but its minor component was different in containing heparin. The main mucopolysaccharide in the ascites of AH-100B bearing rat was hyaluronic acid, which was similar to that of control ascites induced by injection of polypeptone, but minor component contained heparin derived from the cells. The content of hyaluronic acid in the liver of a rat bearing this hepatoma was higher than those of control liver and liver of a rat bearing other tumors. There were no significant differences between control kidney and kidney of a rat bearing this hepatoma."} {"id": "PMID:171193", "title": "Effect of oil-attached BCG cell wall on the kinetics of lymphocytes in the tumor-draining node.", "content": "The lymphocyte distribution into the tumor-draining node was studied with AH-130 hepatoma cells and Donryu strain rats in relation to the adjuvant activity of the oil-attached BCG whole cell wall. The mixed inoculation of the oil-attached BCG cell wall with tumor cells resulted initially in further augmentation of increased distribution of 51Cr-labeled lymphocytes into the draining-node induced by inoculation of the tumor cells alone, and secondarily in the systemic stimulation of response of the lymph node lymphocytes to phytohemagglutinin. Suppression of the inoculated tumor growth and lymph node metastasis was finally observed. These results were discussed in connection with the therapeutic effect of BCG and its cell wall fraction.", "contents": "Effect of oil-attached BCG cell wall on the kinetics of lymphocytes in the tumor-draining node. The lymphocyte distribution into the tumor-draining node was studied with AH-130 hepatoma cells and Donryu strain rats in relation to the adjuvant activity of the oil-attached BCG whole cell wall. The mixed inoculation of the oil-attached BCG cell wall with tumor cells resulted initially in further augmentation of increased distribution of 51Cr-labeled lymphocytes into the draining-node induced by inoculation of the tumor cells alone, and secondarily in the systemic stimulation of response of the lymph node lymphocytes to phytohemagglutinin. Suppression of the inoculated tumor growth and lymph node metastasis was finally observed. These results were discussed in connection with the therapeutic effect of BCG and its cell wall fraction."} {"id": "PMID:171194", "title": "Effect of serum concentration on adenylate cyclase activities of untransformed BHK cells and polyoma virus-transformed derivatives.", "content": "Adenylate cyclase activities of untransformed hamster BHK 21/13 cells and their polyoma virus-transformed derivatives were compared using the cells cultured in low and high serum concentrations. The untransformed cells that were cultured in a medium containing 10% serum had a slightly higher activity than the transformed cells cultured under the same conditions. When the cells were cultured in a medium containing 0.5% serum that stopped proliferation of untransformed cells, more significant difference was observed in the adenylate cyclase activity; the untransformed cells had a two-fold higher activity than the transformed cells. The full activity measured in the presence of fluoride was two-fold higher in the untransformed than in the transformed cells. The low serum concentration increased the enzyme activity of both untransformed and transformed cells, but the enzyme activity of transformed cells in the presence of 0.5% serum did not exceed the activity of untransformed cells in 10% serum. Intracellular cyclic AMP levels were in parallel with the activity of adenylate cyclase, whereas no correlation was found between cyclic AMP levels and cyclic AMP phosphodiesterase activities.", "contents": "Effect of serum concentration on adenylate cyclase activities of untransformed BHK cells and polyoma virus-transformed derivatives. Adenylate cyclase activities of untransformed hamster BHK 21/13 cells and their polyoma virus-transformed derivatives were compared using the cells cultured in low and high serum concentrations. The untransformed cells that were cultured in a medium containing 10% serum had a slightly higher activity than the transformed cells cultured under the same conditions. When the cells were cultured in a medium containing 0.5% serum that stopped proliferation of untransformed cells, more significant difference was observed in the adenylate cyclase activity; the untransformed cells had a two-fold higher activity than the transformed cells. The full activity measured in the presence of fluoride was two-fold higher in the untransformed than in the transformed cells. The low serum concentration increased the enzyme activity of both untransformed and transformed cells, but the enzyme activity of transformed cells in the presence of 0.5% serum did not exceed the activity of untransformed cells in 10% serum. Intracellular cyclic AMP levels were in parallel with the activity of adenylate cyclase, whereas no correlation was found between cyclic AMP levels and cyclic AMP phosphodiesterase activities."} {"id": "PMID:171195", "title": "Effect of gastro-entero-pancreatic endocrine hormones on the histogenesis of gastric cancer in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine; with special reference to development of scirrhous gastric cancer.", "content": "One of five gastro-entero-pancreatic hormones, gastrin, serotonin, histamine, glucagon, and insulin, was intraperitoneally administered for a long period to the rats that received N-methy-N'-nitro-N-nitrosoguanidine. A frequent development of scirrhous carcinoma was demonstrated in the group treated with gastrin.", "contents": "Effect of gastro-entero-pancreatic endocrine hormones on the histogenesis of gastric cancer in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine; with special reference to development of scirrhous gastric cancer. One of five gastro-entero-pancreatic hormones, gastrin, serotonin, histamine, glucagon, and insulin, was intraperitoneally administered for a long period to the rats that received N-methy-N'-nitro-N-nitrosoguanidine. A frequent development of scirrhous carcinoma was demonstrated in the group treated with gastrin."} {"id": "PMID:171197", "title": "Age-dependent arginine phosphokinase activity changes in male vestigial and wild-type Drosophila melanogaster.", "content": "The activity of arginine phosphokinase, an important muscle enzyme in insects, was investigated with age in vestigial-winged and wild-type Drosophila melanogaster. Identical patterns of age-dependent activity changes were observed in the vestigial-winged flies as in the wild-type, even though vestigial-winged flies exhibit a 50% mortality approximately two thirds that of the wild-type as well as being incapable of flight. Results indicate that the age-dependent changes in arginine phosphokinase activity are intrinsically regulated within the cells of the flight muscle.", "contents": "Age-dependent arginine phosphokinase activity changes in male vestigial and wild-type Drosophila melanogaster. The activity of arginine phosphokinase, an important muscle enzyme in insects, was investigated with age in vestigial-winged and wild-type Drosophila melanogaster. Identical patterns of age-dependent activity changes were observed in the vestigial-winged flies as in the wild-type, even though vestigial-winged flies exhibit a 50% mortality approximately two thirds that of the wild-type as well as being incapable of flight. Results indicate that the age-dependent changes in arginine phosphokinase activity are intrinsically regulated within the cells of the flight muscle."} {"id": "PMID:171198", "title": "Instability of the duration of G1 phase of Yoshida sarcoma and ascites hepatomas.", "content": "The durations and coefficients of variance of G1, S and G2 phase were obtained for 8 cell lines of ascites tumours originated from hepatomas in rats, and these were compared. Although changes in the durations of S and G2 phases were small, the duration of G1 phase increased with the cell cycle time. The coefficient of variance of G1 phase was larger than that of S and G2 phases, most remarkedly at short cycle time. It was concluded that the G1 phase is the most unstable as well as the most variable in its duration.", "contents": "Instability of the duration of G1 phase of Yoshida sarcoma and ascites hepatomas. The durations and coefficients of variance of G1, S and G2 phase were obtained for 8 cell lines of ascites tumours originated from hepatomas in rats, and these were compared. Although changes in the durations of S and G2 phases were small, the duration of G1 phase increased with the cell cycle time. The coefficient of variance of G1 phase was larger than that of S and G2 phases, most remarkedly at short cycle time. It was concluded that the G1 phase is the most unstable as well as the most variable in its duration."} {"id": "PMID:171201", "title": "[Selective pancreatic angiography and retrograde pancreatic cholangiography as a combined examination].", "content": "The diagnostic value of selective pancreatic angiography and retrograde pancreatic cholangiography used in combination was studied in 24 patients with chronic pancreatitis or pancreatico-duodenal carcinomas. This was done as a prospective study. The accuracy of the individual methods is 75% and 79% respectively; used in combination, a correct diagnosis is obtained in 91% of cases. The advantage of combining the techniques depends on the fact that they supplement each other.", "contents": "[Selective pancreatic angiography and retrograde pancreatic cholangiography as a combined examination]. The diagnostic value of selective pancreatic angiography and retrograde pancreatic cholangiography used in combination was studied in 24 patients with chronic pancreatitis or pancreatico-duodenal carcinomas. This was done as a prospective study. The accuracy of the individual methods is 75% and 79% respectively; used in combination, a correct diagnosis is obtained in 91% of cases. The advantage of combining the techniques depends on the fact that they supplement each other."} {"id": "PMID:171202", "title": "[Computerized axial tomography of the skull - diagnostic possibilities and clinical results (author's transl)].", "content": "Computerized axial tomography is a new method of tissue examination with x-rays whereby a picture can be produced which is a representation of a slice of the skull. This is done by irradiating the skull from 180 or 225 incremental angles and measuring the absorption at each of these angles. Then with the aid of a computer a tomogram is produced which can be displayed on a screen. These tomograms are representations of a cross-section of the skull composed of 160 X 160 points showing the various intracranial structures with great detail. The present study demonstrates the diagnostic possibilities of the high definition matrix with reference to brain disorders in a large sample of patients for the first time. Some tumours are shown as areas of decreased absorption compared with normal brain tissue. Others, however, have been found to have higher absorption values. With glioblastomas very contrasting pictures are produced with coexistng areas of decreased, increased and similar values to brain tissue. The most important finding is the visualization of brain oedema which appears as a low density area. A grading system of brain oedemas is proposed. The brain oedema associated with tumours has been found to propagate mainly in the white matter producing finger-like shapes. Out of 209 intracranial tumours 203 were recognized in the plain scan, a further five after contrast enhancement. In patients who have suffered from a stroke the differentiation between haemorrhage and infarction is made simple due to the contrasting appearance between the two types of lesion. Location, size and propagation direction of a haematoma as well as rupture of a haemorrhage into the ventricular system can be defined exactly. With brain infarction the hypoxically damaged tissue is well delineated and readily attributable to a given vascular area. In head injuries, for the first time it is possible to differentiate brain contusion with oedema from intracerebral haematoma. Coup and contre-coup are demonstrated. All types of acute intracranial haematomas may be diagnosed easily. With chronic subdural haematomas the new method fails if the contents of the haematoma shows the same absorption values as brain tissue. Late sequelae of head trauma such as contusion defects and necrosis of tissue after oedema can be seen in the tomogram. With infantile hydrocephalus, subdural effusions and malformations of the brain, computerized axial tomography offers a complete diagnosis so that other invasive, neuroradiological investigations may be avoided. Orbital tumors are picked out with great clarity. The high definition matrix allows the demonstration of the optic nerve, the lense and the suspension of the eyeball. Without doubt in the coming years computerized axial tomography will play a dominant role in the diagnosis of brain disorders.", "contents": "[Computerized axial tomography of the skull - diagnostic possibilities and clinical results (author's transl)]. Computerized axial tomography is a new method of tissue examination with x-rays whereby a picture can be produced which is a representation of a slice of the skull. This is done by irradiating the skull from 180 or 225 incremental angles and measuring the absorption at each of these angles. Then with the aid of a computer a tomogram is produced which can be displayed on a screen. These tomograms are representations of a cross-section of the skull composed of 160 X 160 points showing the various intracranial structures with great detail. The present study demonstrates the diagnostic possibilities of the high definition matrix with reference to brain disorders in a large sample of patients for the first time. Some tumours are shown as areas of decreased absorption compared with normal brain tissue. Others, however, have been found to have higher absorption values. With glioblastomas very contrasting pictures are produced with coexistng areas of decreased, increased and similar values to brain tissue. The most important finding is the visualization of brain oedema which appears as a low density area. A grading system of brain oedemas is proposed. The brain oedema associated with tumours has been found to propagate mainly in the white matter producing finger-like shapes. Out of 209 intracranial tumours 203 were recognized in the plain scan, a further five after contrast enhancement. In patients who have suffered from a stroke the differentiation between haemorrhage and infarction is made simple due to the contrasting appearance between the two types of lesion. Location, size and propagation direction of a haematoma as well as rupture of a haemorrhage into the ventricular system can be defined exactly. With brain infarction the hypoxically damaged tissue is well delineated and readily attributable to a given vascular area. In head injuries, for the first time it is possible to differentiate brain contusion with oedema from intracerebral haematoma. Coup and contre-coup are demonstrated. All types of acute intracranial haematomas may be diagnosed easily. With chronic subdural haematomas the new method fails if the contents of the haematoma shows the same absorption values as brain tissue. Late sequelae of head trauma such as contusion defects and necrosis of tissue after oedema can be seen in the tomogram. With infantile hydrocephalus, subdural effusions and malformations of the brain, computerized axial tomography offers a complete diagnosis so that other invasive, neuroradiological investigations may be avoided. Orbital tumors are picked out with great clarity. The high definition matrix allows the demonstration of the optic nerve, the lense and the suspension of the eyeball. Without doubt in the coming years computerized axial tomography will play a dominant role in the diagnosis of brain disorders."} {"id": "PMID:171204", "title": "In vitro studies of calcitonin release in man.", "content": "The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.", "contents": "In vitro studies of calcitonin release in man. The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release."} {"id": "PMID:171206", "title": "Primary tissue culture of normal adult human decapsulated adrenal cortex: radioautographic studies on the metabolic effects of ACTH1-24.", "content": "ACTH-deprived primary normal adult human adrenocortical cells on the 23rd day in vitro were found to lack any DNA synthetic and proliferative activity, but incorporated uridine-3H and 1-leucine-3H actively. In cortical cells of the same age treated for 2 and 7 days with ACTH1-24 (3 X 10(-6) M) the incorporation of the precursors for RNA and DNA synthesis and the cell proliferation were found to be markedly stimulated. The apparent uptake of leucine-3H was instead reduced in 2-day and, less still, in 7-day treated cells. In parallel with ultrastructural studies, these data suggest that ACTH orderly activates the template activity of chromatin while eliciting the differentiation and hypertrophy of human adrenocortical cells.", "contents": "Primary tissue culture of normal adult human decapsulated adrenal cortex: radioautographic studies on the metabolic effects of ACTH1-24. ACTH-deprived primary normal adult human adrenocortical cells on the 23rd day in vitro were found to lack any DNA synthetic and proliferative activity, but incorporated uridine-3H and 1-leucine-3H actively. In cortical cells of the same age treated for 2 and 7 days with ACTH1-24 (3 X 10(-6) M) the incorporation of the precursors for RNA and DNA synthesis and the cell proliferation were found to be markedly stimulated. The apparent uptake of leucine-3H was instead reduced in 2-day and, less still, in 7-day treated cells. In parallel with ultrastructural studies, these data suggest that ACTH orderly activates the template activity of chromatin while eliciting the differentiation and hypertrophy of human adrenocortical cells."} {"id": "PMID:171210", "title": "Electron spin resonance studies on the lipid-protein interaction between cardiolipin and anti-cardiolipin antibodies.", "content": "Electron spin resonance measurements were performed in order to investigate the influence of anti-cardiolipin antibodies on cardiolipin-containing liposomes. The physical state of the lipid structures and the alterations caused by the interaction with specific antibody were determined by measuring the freedom of motion of spin-labeled stearic acid derivatives incorporated into the lipid structures. The interaction of the cardiolipin-containing liposomes with the anti-cardiolipin antibodies reduced the mobility of the spin-labeled stearic acid probe I (12, 3), whose nitroxide group is assumed to be located near the polar region of the lipid bilayer. The restricted mobility, which qualitatively resembles the interaction of cardiolipin liposomes with calcium ions, is probably the result of a tighter packing of the polar groups in their crystalline array. The binding sites of the cardiolipin structures for anti-cardiolipin antibodies and Ca2 ions seem to be identical. As indicated by the spin-labeled stearic acid probe I (1, 14), the apolar region of the lipid bilayer is not affected by the interaction of the cardiolipin-containing liposomes with the anti-cardiolipin antibodies.", "contents": "Electron spin resonance studies on the lipid-protein interaction between cardiolipin and anti-cardiolipin antibodies. Electron spin resonance measurements were performed in order to investigate the influence of anti-cardiolipin antibodies on cardiolipin-containing liposomes. The physical state of the lipid structures and the alterations caused by the interaction with specific antibody were determined by measuring the freedom of motion of spin-labeled stearic acid derivatives incorporated into the lipid structures. The interaction of the cardiolipin-containing liposomes with the anti-cardiolipin antibodies reduced the mobility of the spin-labeled stearic acid probe I (12, 3), whose nitroxide group is assumed to be located near the polar region of the lipid bilayer. The restricted mobility, which qualitatively resembles the interaction of cardiolipin liposomes with calcium ions, is probably the result of a tighter packing of the polar groups in their crystalline array. The binding sites of the cardiolipin structures for anti-cardiolipin antibodies and Ca2 ions seem to be identical. As indicated by the spin-labeled stearic acid probe I (1, 14), the apolar region of the lipid bilayer is not affected by the interaction of the cardiolipin-containing liposomes with the anti-cardiolipin antibodies."} {"id": "PMID:171211", "title": "[Isolation and separation of nucleic acids from Streptomyces hydrogenans (author's transl)].", "content": "Different methods for homogenization of cells of Streptomyces hydrogenans, for extraction of nucleic acids and for fractionation of the RNA and DNA obtained were critically examined. The only way to prepare high molecular weight rapidly labelled RNA and polysomes was to grind freeze-dried cells together with kieselguhr with a mortar and pestle. The best results for extraction of nucleic acids from the cell homogenate were obtained in the presence of diethyl pyrocarbonate (diethyl oxydiformate), yielding nucleic acids of considerable purity in a minimal amount of time. The best resolution of extracted nucleic acids was achieved by electrophoresis in 2% agarose acrylamide gels. This technique proved that during the cell homogenization and extraction procedure the bulk of nucliec acids was not degraded to low molecular weight material. An improved device for the registration of the profile of the absorption after gel electrophoresis is described.", "contents": "[Isolation and separation of nucleic acids from Streptomyces hydrogenans (author's transl)]. Different methods for homogenization of cells of Streptomyces hydrogenans, for extraction of nucleic acids and for fractionation of the RNA and DNA obtained were critically examined. The only way to prepare high molecular weight rapidly labelled RNA and polysomes was to grind freeze-dried cells together with kieselguhr with a mortar and pestle. The best results for extraction of nucleic acids from the cell homogenate were obtained in the presence of diethyl pyrocarbonate (diethyl oxydiformate), yielding nucleic acids of considerable purity in a minimal amount of time. The best resolution of extracted nucleic acids was achieved by electrophoresis in 2% agarose acrylamide gels. This technique proved that during the cell homogenization and extraction procedure the bulk of nucliec acids was not degraded to low molecular weight material. An improved device for the registration of the profile of the absorption after gel electrophoresis is described."} {"id": "PMID:171212", "title": "Purification and characterization of neuraminidase from Clostridium perfringens.", "content": "Clostridium perfringens cells were cultivated on a large scale using an automatic system. Neuraminidase secreted by the cells into the culture medium was purified 380 000-fold by: precipitation with ammonium sulfate between 50 and 85% saturation, filtration on Sephadex G-75, electrophoresis on polyacrylamide gel, and by isoelectric focusing. Three enzyme fractions with different migration rates were obtained by preparative disc electrophoresis in polyacrylamide gel, and five fractions with isoelectric points between pH 4.7 and 5.4 were observed after isoelectric focusing. This microheterogeneity disappeared after denaturation of the enzyme in 0.1% sodium dodecylsulfate or 8M urea. The isoelectric point of the denatured enzyme corresponded to pH 4.3. All enzyme fractions were identical with regard to their immunological and kinetic properties; they had the same molecular weights. The origin of the different \"conformers\" of neuraminidase is discussed. The existence of genuine isoenzymes could largely be excluded. The yield of neuraminidase was 65%, which corresponded to about 10 mg of pure enzyme from 100 l of culture medium. The enzyme was free of protease and various other glycosidase activities. The neuraminidase preparation appeared not to be contaminated by other proteins as judged by electrophoretic analysis using either the native enzyme or the enzyme denatured by sodium dodecylsulfate or urea; ultracentrifugation; chromatography on Sephadex G-200; and immunological methods. The molecular weights of the native or denatured enzyme were found to be in the range between 60 000 and 69 000 (on an average 63 750) using four independent methods. The existence of subunits of neuraminidase was excluded. The neuraminidase exhibited a spec. act. of 580 or 615 U/mg protein with glycopeptides from edible birds' nests or sialyllactose, respectively, as substrates. Additional kinetic properties and the UV-absorption spectrum of the enzyme are described.", "contents": "Purification and characterization of neuraminidase from Clostridium perfringens. Clostridium perfringens cells were cultivated on a large scale using an automatic system. Neuraminidase secreted by the cells into the culture medium was purified 380 000-fold by: precipitation with ammonium sulfate between 50 and 85% saturation, filtration on Sephadex G-75, electrophoresis on polyacrylamide gel, and by isoelectric focusing. Three enzyme fractions with different migration rates were obtained by preparative disc electrophoresis in polyacrylamide gel, and five fractions with isoelectric points between pH 4.7 and 5.4 were observed after isoelectric focusing. This microheterogeneity disappeared after denaturation of the enzyme in 0.1% sodium dodecylsulfate or 8M urea. The isoelectric point of the denatured enzyme corresponded to pH 4.3. All enzyme fractions were identical with regard to their immunological and kinetic properties; they had the same molecular weights. The origin of the different \"conformers\" of neuraminidase is discussed. The existence of genuine isoenzymes could largely be excluded. The yield of neuraminidase was 65%, which corresponded to about 10 mg of pure enzyme from 100 l of culture medium. The enzyme was free of protease and various other glycosidase activities. The neuraminidase preparation appeared not to be contaminated by other proteins as judged by electrophoretic analysis using either the native enzyme or the enzyme denatured by sodium dodecylsulfate or urea; ultracentrifugation; chromatography on Sephadex G-200; and immunological methods. The molecular weights of the native or denatured enzyme were found to be in the range between 60 000 and 69 000 (on an average 63 750) using four independent methods. The existence of subunits of neuraminidase was excluded. The neuraminidase exhibited a spec. act. of 580 or 615 U/mg protein with glycopeptides from edible birds' nests or sialyllactose, respectively, as substrates. Additional kinetic properties and the UV-absorption spectrum of the enzyme are described."} {"id": "PMID:171213", "title": "[15-Hydroxyprostaglandin dehydrogenase from human placenta, II. Steady state kinetics and influence of prostaglandin F2alpha analogues (author's transl)].", "content": "A complete initial rate analysis of the forward reaction catalyzed by 15-hydroxyprostaglandin dehydrogenase from human term placenta was carried out at pH 7.4 (100mM triethanolamine) with the substrates NAD, and the prostaglandins E1, E2 and F2alpha. The limiting Michaelis constants, the dissociation constants, and the limiting maximum velocities for these substrates were calculated by fitting the obtained data by weighted linear regression analysis to the complete rate equation. The product inhibition of the reaction by NADH and 15-oxoprostaglandin was studied and the inhibition constants were graphically determined. The initial rate and inhibition patterns obtained indicate that the reaction follows kinetically an ordered Bi Bi mechanism. The prostaglandin F2alpha analogues ICI 81,008 and ICI 79,939 were not utilized by the enzyme. With ICI 81,008 a slight inhibition of the enzymatic reaction with prostaglandin F2alpha was observed, whereas ICI 79,939 showed no effect. The results are discussed with respect to their possible biological significance.", "contents": "[15-Hydroxyprostaglandin dehydrogenase from human placenta, II. Steady state kinetics and influence of prostaglandin F2alpha analogues (author's transl)]. A complete initial rate analysis of the forward reaction catalyzed by 15-hydroxyprostaglandin dehydrogenase from human term placenta was carried out at pH 7.4 (100mM triethanolamine) with the substrates NAD, and the prostaglandins E1, E2 and F2alpha. The limiting Michaelis constants, the dissociation constants, and the limiting maximum velocities for these substrates were calculated by fitting the obtained data by weighted linear regression analysis to the complete rate equation. The product inhibition of the reaction by NADH and 15-oxoprostaglandin was studied and the inhibition constants were graphically determined. The initial rate and inhibition patterns obtained indicate that the reaction follows kinetically an ordered Bi Bi mechanism. The prostaglandin F2alpha analogues ICI 81,008 and ICI 79,939 were not utilized by the enzyme. With ICI 81,008 a slight inhibition of the enzymatic reaction with prostaglandin F2alpha was observed, whereas ICI 79,939 showed no effect. The results are discussed with respect to their possible biological significance."} {"id": "PMID:171214", "title": "The fine structure of so-called minute pulmonary chemodectomas.", "content": "Electron microscopy was performed on several minute tumors of the type called chemodectomas, all from the lung of a single patient. The cells had a whorling pattern with extensive interdigitating cytoplasmic processes joined by desmosomes. Except for tangles of cytoplasmic fibrils, the tumor cells had few distinctive organelles. They had no endocrine-like granules and were not associated with nerves or basement membranes. The tumors had little resemblance to paragangliomas, but displayed a puzzling similarity to meningiomas. Our observations permit no definite conclusions as to the histogenesis of these lung tumors. Viewed in the light of recent physiologic studies, they cast doubt on the presence of special chemoreceptive paraganglia in the lung.", "contents": "The fine structure of so-called minute pulmonary chemodectomas. Electron microscopy was performed on several minute tumors of the type called chemodectomas, all from the lung of a single patient. The cells had a whorling pattern with extensive interdigitating cytoplasmic processes joined by desmosomes. Except for tangles of cytoplasmic fibrils, the tumor cells had few distinctive organelles. They had no endocrine-like granules and were not associated with nerves or basement membranes. The tumors had little resemblance to paragangliomas, but displayed a puzzling similarity to meningiomas. Our observations permit no definite conclusions as to the histogenesis of these lung tumors. Viewed in the light of recent physiologic studies, they cast doubt on the presence of special chemoreceptive paraganglia in the lung."} {"id": "PMID:171215", "title": "Prenatal diagnosis of I-cell disease.", "content": "A pregnancy from a family in risk of I-cell disease was monitored. The fetus was diagnosed as having I-cell disease based on the findings that (1) lysosomal enzyme activities except for acid phosphatase and alpha glucosidase were clearly elevated in amniotic fluid and were reduced in cultivated amniotic fluid cells, and (2) cytoplasmic inclusions were seen in cultivated amniotic cells by phase contrast microscopy. The accuracy of prediction was confirmed by cultured skin fibroblast of the aborted fetus.", "contents": "Prenatal diagnosis of I-cell disease. A pregnancy from a family in risk of I-cell disease was monitored. The fetus was diagnosed as having I-cell disease based on the findings that (1) lysosomal enzyme activities except for acid phosphatase and alpha glucosidase were clearly elevated in amniotic fluid and were reduced in cultivated amniotic fluid cells, and (2) cytoplasmic inclusions were seen in cultivated amniotic cells by phase contrast microscopy. The accuracy of prediction was confirmed by cultured skin fibroblast of the aborted fetus."} {"id": "PMID:171220", "title": "[Studies on the glucocorticoid control of zinc metabolism].", "content": "In the present paper a possible connection between ACTH stress, cortisol release and serum zinc level is studied. It could be shown that under ACTH stress the reaction of cortisol release is physiological, whereas the zinc level in serum decreases significantly. These reactions recur under insulin stress in a weaker form. On the basis of these results a possible connection between stress situations and hypozincemia was discussed. At the same time a possible misinterpretation with regard to a general zinc deficiency under the condition of a reduced serum zinc level in stress situations is pointed out. In accordance with other authors it can, however, be said that the zinc metabolism probably depends on glucocorticoidal controls.", "contents": "[Studies on the glucocorticoid control of zinc metabolism]. In the present paper a possible connection between ACTH stress, cortisol release and serum zinc level is studied. It could be shown that under ACTH stress the reaction of cortisol release is physiological, whereas the zinc level in serum decreases significantly. These reactions recur under insulin stress in a weaker form. On the basis of these results a possible connection between stress situations and hypozincemia was discussed. At the same time a possible misinterpretation with regard to a general zinc deficiency under the condition of a reduced serum zinc level in stress situations is pointed out. In accordance with other authors it can, however, be said that the zinc metabolism probably depends on glucocorticoidal controls."} {"id": "PMID:171221", "title": "Immunisation trials with live attenuated cytomegalovirus TOWNE 125.", "content": "Trials with live cytomegalovirus (TOWNE 125 strain), which was attenuated by 125 passages exclusively on WI-38 cells, were done in adult volunteers. No virus take occured after oral/nasal application. When 10(3) TCD50 was given intramuscularly an IgG antibody response was detected at four weeks in all of ten volunteers tested by immunofluorescence; an IgM response was found in seven. Only mild local side-effects and relative lymphocytosis were observed. No virus excretion was found. Many questions remain to be answered by further trials before a cytomegalovirus vaccine can be given to adolescent girls.", "contents": "Immunisation trials with live attenuated cytomegalovirus TOWNE 125. Trials with live cytomegalovirus (TOWNE 125 strain), which was attenuated by 125 passages exclusively on WI-38 cells, were done in adult volunteers. No virus take occured after oral/nasal application. When 10(3) TCD50 was given intramuscularly an IgG antibody response was detected at four weeks in all of ten volunteers tested by immunofluorescence; an IgM response was found in seven. Only mild local side-effects and relative lymphocytosis were observed. No virus excretion was found. Many questions remain to be answered by further trials before a cytomegalovirus vaccine can be given to adolescent girls."} {"id": "PMID:171223", "title": "Pathogenicity of entamoeba histolytica.", "content": "The pathogenicity of Entamoeba histolytica is discussed from an immunologic point of view. The evidence that there is some \"trigger\" mechanism which converts a commensal dwelling organism into a tissue invasive pathogen is rejected as inadequate. The number of liver abscess cases in comparison with the number of intestinal amebic infections in a population is so low that this in itself suggests that tissue invasion is a rare event in the life history of the ameba. A review is made of the experimental evidence that some type of sensitization is necessary before ameba can invade tissue. In postulating an immunologic basis for the pathogenicity of ameba, a parallel between the behavior of malignant cells in the body and an amebic infection in the gut is made. An appealing hypothesis which deserves further research effort is that an altered immune response is the basis for the pathogenic mechanism in the host.", "contents": "Pathogenicity of entamoeba histolytica. The pathogenicity of Entamoeba histolytica is discussed from an immunologic point of view. The evidence that there is some \"trigger\" mechanism which converts a commensal dwelling organism into a tissue invasive pathogen is rejected as inadequate. The number of liver abscess cases in comparison with the number of intestinal amebic infections in a population is so low that this in itself suggests that tissue invasion is a rare event in the life history of the ameba. A review is made of the experimental evidence that some type of sensitization is necessary before ameba can invade tissue. In postulating an immunologic basis for the pathogenicity of ameba, a parallel between the behavior of malignant cells in the body and an amebic infection in the gut is made. An appealing hypothesis which deserves further research effort is that an altered immune response is the basis for the pathogenic mechanism in the host."} {"id": "PMID:171224", "title": "Adjuvant activity of the histamine-sensitizing factor of Bordetella pertussis in different strains of mice.", "content": "The effect of an extract of histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of different strains of mice to ovalbumin (OA) was investigated with regard to optimal dose of antigen and adjuvant. It was observed that all strains of mice treated with HSF during immunization with OA demonstrated enhanced production of hemagglutinating antibodies, as compared to animals treated with antigen alone. This enhancement was generally not as great as that demonstrated when Al(OH)3 was the adjuvant. HSF also stimulated a reaginic antibody response (IgE) to OA, but not in all strains of mice. In reagin responders optimal responses were observed with high doses of both antigen and adjuvant, whereas low doses of both produced little or no response. Maximal reagin production occurred usually 14-28 days after immunization and persisted for long periods of time. An anamnestic reagin response was elicited upon secondary immunization with antigen alone, not only in mice immunized with OA and HSF but also in animals treated with OA alone. These studies demonstrate the profound effect that a microbial substance such as HSF can have on reaginic antibody production and suggest that the stimulation of IgE antibody production is the net result of a number of factors including genetic capabilities of the host, environmental influence such as adjuvants, and prior exposure to an antigen.", "contents": "Adjuvant activity of the histamine-sensitizing factor of Bordetella pertussis in different strains of mice. The effect of an extract of histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of different strains of mice to ovalbumin (OA) was investigated with regard to optimal dose of antigen and adjuvant. It was observed that all strains of mice treated with HSF during immunization with OA demonstrated enhanced production of hemagglutinating antibodies, as compared to animals treated with antigen alone. This enhancement was generally not as great as that demonstrated when Al(OH)3 was the adjuvant. HSF also stimulated a reaginic antibody response (IgE) to OA, but not in all strains of mice. In reagin responders optimal responses were observed with high doses of both antigen and adjuvant, whereas low doses of both produced little or no response. Maximal reagin production occurred usually 14-28 days after immunization and persisted for long periods of time. An anamnestic reagin response was elicited upon secondary immunization with antigen alone, not only in mice immunized with OA and HSF but also in animals treated with OA alone. These studies demonstrate the profound effect that a microbial substance such as HSF can have on reaginic antibody production and suggest that the stimulation of IgE antibody production is the net result of a number of factors including genetic capabilities of the host, environmental influence such as adjuvants, and prior exposure to an antigen."} {"id": "PMID:171225", "title": "Effect of exogenous cyclic AMP and other adenine nucleotides on neutrophil chemotaxis and motility.", "content": "Cyclic AMP placed in the bottom of the modified Boyden chemotaxis chamber is weakly chemotactic for rabbit peritoneal neutrophils. Dibutyryl-cyclic AMP under similar conditions gives a biphasic response, being weakly chemotactic at low concentrations and inhibiting cell movement at higher concentrations. When mixed with the cells in the upper compartment of the chemotaxis chamber, cyclic AMP and dibutyryl-cyclic AMP enhance neutrophil spontaneous motility; on the other hand, dibutyryl-cyclic AMP mixed with the cells in the upper compartment consistently inhibits neutrophil chemotactic responsiveness, while cyclic AMP has a variable effect on chemotaxis. The effect of ADP and ATP was to inhibit chemotaxis and spontaneous motility. AMP is totally without effect.", "contents": "Effect of exogenous cyclic AMP and other adenine nucleotides on neutrophil chemotaxis and motility. Cyclic AMP placed in the bottom of the modified Boyden chemotaxis chamber is weakly chemotactic for rabbit peritoneal neutrophils. Dibutyryl-cyclic AMP under similar conditions gives a biphasic response, being weakly chemotactic at low concentrations and inhibiting cell movement at higher concentrations. When mixed with the cells in the upper compartment of the chemotaxis chamber, cyclic AMP and dibutyryl-cyclic AMP enhance neutrophil spontaneous motility; on the other hand, dibutyryl-cyclic AMP mixed with the cells in the upper compartment consistently inhibits neutrophil chemotactic responsiveness, while cyclic AMP has a variable effect on chemotaxis. The effect of ADP and ATP was to inhibit chemotaxis and spontaneous motility. AMP is totally without effect."} {"id": "PMID:171226", "title": "Nasopharyngeal carcinoma. IX. Antibodies to EBNA and correlation with response to other ebv antigens in chinese patients.", "content": "Ninety-five sera from Chinese NPC patients in different stages of the disease, 38 sera from Chinese patients with other cancers, and 50 normal Chinese sera, were titrated for EBNA, VCA, EA and complement-fixing (CF/S) EBV-specific antibodies. The geometric mean (GMT) EBNA antibody titre of patients with NPC at stage I was found to be four times higher than that of normal individuals and increased in parallel with clinical deterioration. Antibody titres against EBNA did not correlate with either VCA or EA antibodies but, in general, correlated with CF/S antibodies. EA antibodies correlated relatively well with VCA antibodies and discriminated better than EBNA titre between NPC at stage I and controls.", "contents": "Nasopharyngeal carcinoma. IX. Antibodies to EBNA and correlation with response to other ebv antigens in chinese patients. Ninety-five sera from Chinese NPC patients in different stages of the disease, 38 sera from Chinese patients with other cancers, and 50 normal Chinese sera, were titrated for EBNA, VCA, EA and complement-fixing (CF/S) EBV-specific antibodies. The geometric mean (GMT) EBNA antibody titre of patients with NPC at stage I was found to be four times higher than that of normal individuals and increased in parallel with clinical deterioration. Antibody titres against EBNA did not correlate with either VCA or EA antibodies but, in general, correlated with CF/S antibodies. EA antibodies correlated relatively well with VCA antibodies and discriminated better than EBNA titre between NPC at stage I and controls."} {"id": "PMID:171227", "title": "Colcemid-induced polyploidy and aneuploidy in normal and tumour cells in vitro.", "content": "The frequency of colcemid-induced genome mutations (aneuploidy and polyploidy) in normal and SV40-transformed cultures of Djungarian hamster embryonic cells was studied. Genome mutations were easily induced by the drug in transformed but not in normal cultures. Elevation of colcemid concentration and prolongation of the incubation period did not substantially increase the frequency of genome mutations in normal cells. An attempt was made to study the causes of the differences in sensitivity to colcemid-mutagenicity of normal and transformed cells. Transformed cells did not include more 3H-colchicine than normal cells, and binding of the drug to cell homogenates was similar in both kinds of cultures. According to these data the higher sensitivity of transformed cells to colcemid is not connected either with increased permeability of the cell to the drug or with changes in its binding to tubulin.", "contents": "Colcemid-induced polyploidy and aneuploidy in normal and tumour cells in vitro. The frequency of colcemid-induced genome mutations (aneuploidy and polyploidy) in normal and SV40-transformed cultures of Djungarian hamster embryonic cells was studied. Genome mutations were easily induced by the drug in transformed but not in normal cultures. Elevation of colcemid concentration and prolongation of the incubation period did not substantially increase the frequency of genome mutations in normal cells. An attempt was made to study the causes of the differences in sensitivity to colcemid-mutagenicity of normal and transformed cells. Transformed cells did not include more 3H-colchicine than normal cells, and binding of the drug to cell homogenates was similar in both kinds of cultures. According to these data the higher sensitivity of transformed cells to colcemid is not connected either with increased permeability of the cell to the drug or with changes in its binding to tubulin."} {"id": "PMID:171228", "title": "Interactions between endogenous baboon type-C virus and oncogenic viruses. I. Syncytium induction and development of infectivity assay.", "content": "Cells releasing the endogenous baboon virus (BV) can interact with human KC cells containing the Rous sarcoma virus (RSV) genome, resulting in cell fusion and syncytium formation. This interaction has been utilized in the development of a sensitive infectivity assay for BV. The titration pattern is of a one-hit type, demonstrating a linear relationship between virus concentration and number of syncytial plaques obtained in the KC co-cultivation assay. Endpoint titration comparisons indicate that the KC test is as sensitive as the immunofluorescence or the RNA-directed DNA-polymerase assays. Attempts to develop an XC test for BV failed, indicating that while BV can interact with the RSV genome it will do so in the human KC cells and not in the rat XC cells. Syncytia are also induced when KC cells are directly exposed to cell-free BV; however, a linear dose relationship is not obtained. When syncytium-positive KC cultures are passaged, the syncytia disappear and a chronic BV infection is established. These KC-BV cells then lose the ability to interact with either the endogenous cat RD-114 virus or the Mason-Pfizer virus which are known to form syncytia with KC cells.", "contents": "Interactions between endogenous baboon type-C virus and oncogenic viruses. I. Syncytium induction and development of infectivity assay. Cells releasing the endogenous baboon virus (BV) can interact with human KC cells containing the Rous sarcoma virus (RSV) genome, resulting in cell fusion and syncytium formation. This interaction has been utilized in the development of a sensitive infectivity assay for BV. The titration pattern is of a one-hit type, demonstrating a linear relationship between virus concentration and number of syncytial plaques obtained in the KC co-cultivation assay. Endpoint titration comparisons indicate that the KC test is as sensitive as the immunofluorescence or the RNA-directed DNA-polymerase assays. Attempts to develop an XC test for BV failed, indicating that while BV can interact with the RSV genome it will do so in the human KC cells and not in the rat XC cells. Syncytia are also induced when KC cells are directly exposed to cell-free BV; however, a linear dose relationship is not obtained. When syncytium-positive KC cultures are passaged, the syncytia disappear and a chronic BV infection is established. These KC-BV cells then lose the ability to interact with either the endogenous cat RD-114 virus or the Mason-Pfizer virus which are known to form syncytia with KC cells."} {"id": "PMID:171229", "title": "Characterization of non-producer human cells induced by Kirsten sarcoma virus.", "content": "Non-producer (NP) human cells induced by the Kirsten sarcoma virus were characterized. These morphologically altered NP cells produced neither infectious virus nor complement-fixing antigens of the murine sarcoma-leukemia virus complex. The NP cells did not release RNA-dependent DNA polymerase and type-C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H-uridine labelling. The NP cells produced tumors when transplanted subcutaneously into athymic nude mice. The tumor cells re-established in culture resembled the orginal NP cells, were confirmed as human cells by karyological analysis and were also found to be \"non-producer\". The sarcoma virus genome in NP cells could be rescued not only by co-cultivation with \"helper virus\"-releasing cells but also by superinfection with helper type-C viruses. Murine (Rauscher, Ki-MuLV, AT-124 and two other xenotropic viruses), feline, RD-114 and Simian (woolly monkey and baboon) type-C viruses possessed the ability to rescue the sarcoma genome from NP cells but not AKR leukemia virus. In addition, the feline leukemia virus titer obtained by the rescuing technique in NP cells was the same as those obtained in feline embryo and NP cells by CF induction assay.", "contents": "Characterization of non-producer human cells induced by Kirsten sarcoma virus. Non-producer (NP) human cells induced by the Kirsten sarcoma virus were characterized. These morphologically altered NP cells produced neither infectious virus nor complement-fixing antigens of the murine sarcoma-leukemia virus complex. The NP cells did not release RNA-dependent DNA polymerase and type-C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H-uridine labelling. The NP cells produced tumors when transplanted subcutaneously into athymic nude mice. The tumor cells re-established in culture resembled the orginal NP cells, were confirmed as human cells by karyological analysis and were also found to be \"non-producer\". The sarcoma virus genome in NP cells could be rescued not only by co-cultivation with \"helper virus\"-releasing cells but also by superinfection with helper type-C viruses. Murine (Rauscher, Ki-MuLV, AT-124 and two other xenotropic viruses), feline, RD-114 and Simian (woolly monkey and baboon) type-C viruses possessed the ability to rescue the sarcoma genome from NP cells but not AKR leukemia virus. In addition, the feline leukemia virus titer obtained by the rescuing technique in NP cells was the same as those obtained in feline embryo and NP cells by CF induction assay."} {"id": "PMID:171230", "title": "Popper's philosophy for epidemiologists.", "content": "This paper discusses the application of Popper's philosophy to epidemiological research, examining in particular the problems of replication without risk of refutation, of mistaking statistical sophistication for deductive inference, and of dealing with causality at a general level. An example is given of a Popperian approach to the test of a causal hypothesis concerning cancer of the cervix.", "contents": "Popper's philosophy for epidemiologists. This paper discusses the application of Popper's philosophy to epidemiological research, examining in particular the problems of replication without risk of refutation, of mistaking statistical sophistication for deductive inference, and of dealing with causality at a general level. An example is given of a Popperian approach to the test of a causal hypothesis concerning cancer of the cervix."} {"id": "PMID:171232", "title": "Adrenocorticotropic (ACTH) cells of rats after head irradiation.", "content": "The heads of intact rats and of rats 15 days after adrenalectomy were irradiated with 1200 R. Some of the adrenalectomized animals with irradiated heads were treated with 5 mg of deoxycorticosterone acetate. In adrenocorticotropic cells of adrenalectomized rats 15 and 30 days after irradiation, the decreased amount of the granular endoplasmic reticulum and the Golgi regression imply a considerably decreased protein synthesis. The finding of an increased number of granules and of granules larger than normal suggests that they are the result of slowed down transport and secretion of the products of these cells' activities. After head irradiation an increased number of degenerative cells was evident in the pituitary of both intact and adrenalectomized rats. The degree of the degenerative changes and the number of degenerative cells was higher 30 than 15 days after irradiation and both were decreased if the adrenalectomized rats were treated with deoxycorticosterone acetate.", "contents": "Adrenocorticotropic (ACTH) cells of rats after head irradiation. The heads of intact rats and of rats 15 days after adrenalectomy were irradiated with 1200 R. Some of the adrenalectomized animals with irradiated heads were treated with 5 mg of deoxycorticosterone acetate. In adrenocorticotropic cells of adrenalectomized rats 15 and 30 days after irradiation, the decreased amount of the granular endoplasmic reticulum and the Golgi regression imply a considerably decreased protein synthesis. The finding of an increased number of granules and of granules larger than normal suggests that they are the result of slowed down transport and secretion of the products of these cells' activities. After head irradiation an increased number of degenerative cells was evident in the pituitary of both intact and adrenalectomized rats. The degree of the degenerative changes and the number of degenerative cells was higher 30 than 15 days after irradiation and both were decreased if the adrenalectomized rats were treated with deoxycorticosterone acetate."} {"id": "PMID:171235", "title": "In vivo characteristics of temperature-sensitive host range mutants of herpes simplex virus type 2.", "content": "The in vivo properties of four host range temperature-sensitive (ts) mutants of herpes simplex virus type 2 (HSV-2) were correlated with known in vitro characteristics. Mutants and parental virus were inoculated into newborn and weanling mice and weanling hamsters by intracranial and subcutaneous routes, and into weanling rabbits by corneal scarification. In all cases the pattern of attenuation of mutants in vivo correlated with their stability in vitro at 39 degrees. The most attenuated mutant (mutant 69) was also the most consistent in its inability to induce cytopathic effects (CPE) in vitro or to replicate under nonpermissive conditions. Conversely, the most virulent mutant (mutant 41) was the least stable under nonpermissive conditions.", "contents": "In vivo characteristics of temperature-sensitive host range mutants of herpes simplex virus type 2. The in vivo properties of four host range temperature-sensitive (ts) mutants of herpes simplex virus type 2 (HSV-2) were correlated with known in vitro characteristics. Mutants and parental virus were inoculated into newborn and weanling mice and weanling hamsters by intracranial and subcutaneous routes, and into weanling rabbits by corneal scarification. In all cases the pattern of attenuation of mutants in vivo correlated with their stability in vitro at 39 degrees. The most attenuated mutant (mutant 69) was also the most consistent in its inability to induce cytopathic effects (CPE) in vitro or to replicate under nonpermissive conditions. Conversely, the most virulent mutant (mutant 41) was the least stable under nonpermissive conditions."} {"id": "PMID:171236", "title": "Heterogeneity of surface antigens on endogenous type C virus-producing cell sublines derived from a clonal line of BALB/3T3 cells.", "content": "When viral envelope antigens (VEAs) and virus-associated cell surface antigens (CSAs) are used as markers of type C viruses, more heterogeneity of virus populations can be demonstrated than by using host range alone. In the present study, four CSAs (PC1, X.1, GCSA, and MEV-SA1) and three VEAs (xVEA, x1-VEA, and sub-gsVEA) were used as markers of virus populations present in various sublines of the BALB/c embryonic fibroblast BALB/3T3 clone A31 line. Of four spontaneously transformed sublines, two released N-tropic endogenous type C viruses spontaneously after long-term culture and each had distinct antigenic patterns. Treatment with 5-bromodoxyuridine (BrdU) resulted in the detection of X-tropic viruses in all four sublines. The expression of these X-tropic viruses was associated with two different antigenic patterns. When the clonal rabbit corneal SIRC cell line was infected with the X-tropic viruses obtained after BrdU treatment, the cells acquired detectable amounts of only one of the antigenic markers.", "contents": "Heterogeneity of surface antigens on endogenous type C virus-producing cell sublines derived from a clonal line of BALB/3T3 cells. When viral envelope antigens (VEAs) and virus-associated cell surface antigens (CSAs) are used as markers of type C viruses, more heterogeneity of virus populations can be demonstrated than by using host range alone. In the present study, four CSAs (PC1, X.1, GCSA, and MEV-SA1) and three VEAs (xVEA, x1-VEA, and sub-gsVEA) were used as markers of virus populations present in various sublines of the BALB/c embryonic fibroblast BALB/3T3 clone A31 line. Of four spontaneously transformed sublines, two released N-tropic endogenous type C viruses spontaneously after long-term culture and each had distinct antigenic patterns. Treatment with 5-bromodoxyuridine (BrdU) resulted in the detection of X-tropic viruses in all four sublines. The expression of these X-tropic viruses was associated with two different antigenic patterns. When the clonal rabbit corneal SIRC cell line was infected with the X-tropic viruses obtained after BrdU treatment, the cells acquired detectable amounts of only one of the antigenic markers."} {"id": "PMID:171239", "title": "The effect of alpha1-24-corticotropin on growth hormone release in prepubertal children.", "content": "The effect of alpha1-24-corticotropin-Zn on the results of pituitary stimulation tests (moderate standardized physical exercise, arginine infusion, insulin-induced hypoglycemia) was studied in 27 prepubertal children with non-endocrine retardation of growth and development. After administration of 1 mg alpha1-24-corticotropin, the basal blood glucose and plasma cortisol levels rose significantly. However, the growth hormone increase after the three stimulation tests was significantly lower than without the corticotropin injection. The results demonstrate the inhibiting effect of alpha1-24-corticotropin on growth hormone secretion.", "contents": "The effect of alpha1-24-corticotropin on growth hormone release in prepubertal children. The effect of alpha1-24-corticotropin-Zn on the results of pituitary stimulation tests (moderate standardized physical exercise, arginine infusion, insulin-induced hypoglycemia) was studied in 27 prepubertal children with non-endocrine retardation of growth and development. After administration of 1 mg alpha1-24-corticotropin, the basal blood glucose and plasma cortisol levels rose significantly. However, the growth hormone increase after the three stimulation tests was significantly lower than without the corticotropin injection. The results demonstrate the inhibiting effect of alpha1-24-corticotropin on growth hormone secretion."} {"id": "PMID:171241", "title": "Fine structural localization of alkaline phosphatase in the granular pneumonocytes of hamster lung.", "content": "The fine structural localization of nonspecific alkaline phosphatase was studied in the granular pneumonocytes (type II alveolar epithelial cells) of hamster lung by incubating sections of glutaraldehyde-fixed tissues in a medium containing lead ions and sodium beta-glycerophosphate or alpha-naphthyl acid phosphate. The specificity of the reaction was tested by exposing the sections to inhibitors of alkaline phosphatase. The results showed that alkaline phosphatase activity was present in the inclusion bodies of granular pneumonocytes. The enzyme reaction was strong in the membrane lining the inclusion bodies and a weaker reaction was generally detectable in the inclusion contents. Although only a proportion of the inclusion bodies showed enzyme activity, there was no obvious correlation between the reactivity of the inclusions and their intracellular position or size. The other organelles were unreactive. The finding of alkaline phosphatase activity within the inclusion bodies of granular pneumonocytes is an enigma as these organelles are generally considered to be lyosomes.", "contents": "Fine structural localization of alkaline phosphatase in the granular pneumonocytes of hamster lung. The fine structural localization of nonspecific alkaline phosphatase was studied in the granular pneumonocytes (type II alveolar epithelial cells) of hamster lung by incubating sections of glutaraldehyde-fixed tissues in a medium containing lead ions and sodium beta-glycerophosphate or alpha-naphthyl acid phosphate. The specificity of the reaction was tested by exposing the sections to inhibitors of alkaline phosphatase. The results showed that alkaline phosphatase activity was present in the inclusion bodies of granular pneumonocytes. The enzyme reaction was strong in the membrane lining the inclusion bodies and a weaker reaction was generally detectable in the inclusion contents. Although only a proportion of the inclusion bodies showed enzyme activity, there was no obvious correlation between the reactivity of the inclusions and their intracellular position or size. The other organelles were unreactive. The finding of alkaline phosphatase activity within the inclusion bodies of granular pneumonocytes is an enigma as these organelles are generally considered to be lyosomes."} {"id": "PMID:171242", "title": "Cytochemical correlates of structural sexual dimorphism in glandular tissues of the mouse. I. Studies of the renal glomerular capsule.", "content": "The parietal epithelium of Bowman's capsule has been analyzed by enzyme cytochemistry in kidneys of mice (C57BL/6J) from birth to 50 days of age. There is a greater tendency for cells in the central portions of the capsular crescent to be cuboidal in post-pubertal males than in pre-pubertal mice of either sex or in post-pubertal females where they are generally squamous; moreover, these heightened capsular cells have a distinct microvillous border. Cytochemical procedures were selected which might confirm the morphological suggestion that the cuboidal parietal epithelium possesses an absorptive capacity. The oxidoreductase activity of the mitochondria of the cuboidal cells of this layer is comparable to that of the columnar cells of the proximal convoluted tubule. The cytochrome oxidase activity of the mitochondria in both of these segments of the nephron is intense. This is in sharp contrast to the unreactive mitochondria in the squamous cells of the parietal epithelium. Furthermore, a striking heterogeneity in the degree of cytochrome oxidase activity is evident in the mitochondria of the cuboidal parietal cells as well as in the cells of the proximal tubules. In the former cells, active mitochondria were generally found near microvilli at the apical ends and in the areas of the basal infoldings whereas those in a central position were more frequently unreactive. The brush border of the cuboidal capsular epithelium had prominent alkaline phosphatase and aminopeptidase activities as has previously been observed in other brush borders. Functional capacity corresponding to the morphological and cytochemical specialization of the cuboidal capsular cells was demonstrated by their uptake of horseradish peroxidase. This exogenous protein tracer could be seen in apical vacuoles and phagosomes in the cuboidal parietal epithelium. The cytochemical resemblance of the cells of this epithelium to those of the proximal convoluted tubules suggests a similar involvement in resorption and perhaps in active transport. A possible relationship of this differentiation of the capsular epithelium to the proteinuria normal for adult male mice is discussed.", "contents": "Cytochemical correlates of structural sexual dimorphism in glandular tissues of the mouse. I. Studies of the renal glomerular capsule. The parietal epithelium of Bowman's capsule has been analyzed by enzyme cytochemistry in kidneys of mice (C57BL/6J) from birth to 50 days of age. There is a greater tendency for cells in the central portions of the capsular crescent to be cuboidal in post-pubertal males than in pre-pubertal mice of either sex or in post-pubertal females where they are generally squamous; moreover, these heightened capsular cells have a distinct microvillous border. Cytochemical procedures were selected which might confirm the morphological suggestion that the cuboidal parietal epithelium possesses an absorptive capacity. The oxidoreductase activity of the mitochondria of the cuboidal cells of this layer is comparable to that of the columnar cells of the proximal convoluted tubule. The cytochrome oxidase activity of the mitochondria in both of these segments of the nephron is intense. This is in sharp contrast to the unreactive mitochondria in the squamous cells of the parietal epithelium. Furthermore, a striking heterogeneity in the degree of cytochrome oxidase activity is evident in the mitochondria of the cuboidal parietal cells as well as in the cells of the proximal tubules. In the former cells, active mitochondria were generally found near microvilli at the apical ends and in the areas of the basal infoldings whereas those in a central position were more frequently unreactive. The brush border of the cuboidal capsular epithelium had prominent alkaline phosphatase and aminopeptidase activities as has previously been observed in other brush borders. Functional capacity corresponding to the morphological and cytochemical specialization of the cuboidal capsular cells was demonstrated by their uptake of horseradish peroxidase. This exogenous protein tracer could be seen in apical vacuoles and phagosomes in the cuboidal parietal epithelium. The cytochemical resemblance of the cells of this epithelium to those of the proximal convoluted tubules suggests a similar involvement in resorption and perhaps in active transport. A possible relationship of this differentiation of the capsular epithelium to the proteinuria normal for adult male mice is discussed."} {"id": "PMID:171243", "title": "The inhibition of alkaline phosphatase by L-p-bromotetramisole.", "content": "A levamisole analogue, the L-p-bromotetramisole is introduced as a potent inhibitor of non-specific alkaline phosphatase. Complete inhibition is achieved cytochemically at a concentration of 0.1 mM in various rat tissues except the intestine, which is not affected. The D-p-bromotetramisole does not influence the alkaline phosphatase activities. Since no effect of the inhibitor is seen on the activities of specific phosphatases, this drug is recommended also as an additive for specific phosphatase media in order to yield the specific activity only.", "contents": "The inhibition of alkaline phosphatase by L-p-bromotetramisole. A levamisole analogue, the L-p-bromotetramisole is introduced as a potent inhibitor of non-specific alkaline phosphatase. Complete inhibition is achieved cytochemically at a concentration of 0.1 mM in various rat tissues except the intestine, which is not affected. The D-p-bromotetramisole does not influence the alkaline phosphatase activities. Since no effect of the inhibitor is seen on the activities of specific phosphatases, this drug is recommended also as an additive for specific phosphatase media in order to yield the specific activity only."} {"id": "PMID:171244", "title": "Electron microscopic observations on the cholesterol distributed in the epithelial cells of the gallbladder.", "content": "Epithelial cells of eight human gallbladders with cholesterosis were examined. In the supranuclear portion of the epithelial cells of one case, many spicular, circular and plate-like crystalline structures are present. Spicular and circular structures have not a limiting membrane, but plate-like structures are apparently bounded by a limiting membrane that clearly shows trilamellar structure. After digitonin treatment, the spicular and circular crystalline structures become denser. On the other hand, the plate-like structures do not become denser by digitonization. In the epithelial cells that contain no crystalline structure, there also occur many reaction precipitates after digitonization. These findings may suggest that free cholesterol is highly present in the epithelial cells of gallbladder with cholesterosis and that it, in some case, precipitates in the form of spicular or circular structure for the rapid fixation process.", "contents": "Electron microscopic observations on the cholesterol distributed in the epithelial cells of the gallbladder. Epithelial cells of eight human gallbladders with cholesterosis were examined. In the supranuclear portion of the epithelial cells of one case, many spicular, circular and plate-like crystalline structures are present. Spicular and circular structures have not a limiting membrane, but plate-like structures are apparently bounded by a limiting membrane that clearly shows trilamellar structure. After digitonin treatment, the spicular and circular crystalline structures become denser. On the other hand, the plate-like structures do not become denser by digitonization. In the epithelial cells that contain no crystalline structure, there also occur many reaction precipitates after digitonization. These findings may suggest that free cholesterol is highly present in the epithelial cells of gallbladder with cholesterosis and that it, in some case, precipitates in the form of spicular or circular structure for the rapid fixation process."} {"id": "PMID:171245", "title": "Studies in lipid histochemistry. XIII. The OPA (osmiumtetroxide-periodic acid-alpha-naphthylamine) method for the detection of apolar lipids.", "content": "A new procedure for the detection of apolar lipids is described. It is a modification of the OTAN method (Adams, 1959) using periodic acid which oxidatively removes lower osmium derivatives from polar sites only, leaving those in apolar lipids intact and demonstrable with alpha-naphthylamine. Control steps for the exclusion of the possible interference of some less polar complex lipids and of lipopigments are described. The described technic is superior to the conventionally used sudan dyes due partly to the fact that only aqueous solutions are employed thus excluding any extraction of lipids, partly to the more distinct coloration.", "contents": "Studies in lipid histochemistry. XIII. The OPA (osmiumtetroxide-periodic acid-alpha-naphthylamine) method for the detection of apolar lipids. A new procedure for the detection of apolar lipids is described. It is a modification of the OTAN method (Adams, 1959) using periodic acid which oxidatively removes lower osmium derivatives from polar sites only, leaving those in apolar lipids intact and demonstrable with alpha-naphthylamine. Control steps for the exclusion of the possible interference of some less polar complex lipids and of lipopigments are described. The described technic is superior to the conventionally used sudan dyes due partly to the fact that only aqueous solutions are employed thus excluding any extraction of lipids, partly to the more distinct coloration."} {"id": "PMID:171246", "title": "Effect of bredinin and its aglycone on L5178Y cells.", "content": "The aglycone of the nucleoside antibiotic, bredinin, was as strongly cytotoxic to L5178Y cells as bredinin. The cytotoxic properties of the aglycone were very similar to those of bredinin and the minimum inhibitory concentrations of both were 10(-5)M. The growth inhibitory effects of both agents regardless of their concentrations, were reversed by guanylic acid, guanosine or guanine. However, on increasing the concentrations of these agents, the reversing effect of guanylic acid decreased gradually, the dose-response curves for the two agents being similar. Both agents inhibited the incorporation of thymidine and uridine, but not leucine into macromolecules in L5178Y cells and their inhibitory effects were reversed to similar extents by guanylic acid. On the other hand, the growth inhibitory effect of the aglycone on L5178Y cells was prevented by adenine only, though not be adenosine or adenylic acid while the effect of bredinin was not prevented by adenine. These results suggest that the aglycone itself does not inhibit growth, but that its effect is due to its conversion to bredinin by an enzyme such as adenine phosphoribosyl transferase. For recovery of growth, three moles of adenine were required per mole of the aglycone. When the aglycone was administered orally to rats, bredinin was administered orally to rats, bredinin was recovered in their serum and urine.", "contents": "Effect of bredinin and its aglycone on L5178Y cells. The aglycone of the nucleoside antibiotic, bredinin, was as strongly cytotoxic to L5178Y cells as bredinin. The cytotoxic properties of the aglycone were very similar to those of bredinin and the minimum inhibitory concentrations of both were 10(-5)M. The growth inhibitory effects of both agents regardless of their concentrations, were reversed by guanylic acid, guanosine or guanine. However, on increasing the concentrations of these agents, the reversing effect of guanylic acid decreased gradually, the dose-response curves for the two agents being similar. Both agents inhibited the incorporation of thymidine and uridine, but not leucine into macromolecules in L5178Y cells and their inhibitory effects were reversed to similar extents by guanylic acid. On the other hand, the growth inhibitory effect of the aglycone on L5178Y cells was prevented by adenine only, though not be adenosine or adenylic acid while the effect of bredinin was not prevented by adenine. These results suggest that the aglycone itself does not inhibit growth, but that its effect is due to its conversion to bredinin by an enzyme such as adenine phosphoribosyl transferase. For recovery of growth, three moles of adenine were required per mole of the aglycone. When the aglycone was administered orally to rats, bredinin was administered orally to rats, bredinin was recovered in their serum and urine."} {"id": "PMID:171247", "title": "Degradation of phospholipid in Pseudomonas aeruginosa induced by polymyxin B.", "content": "Effects of polymyxin B on the synthesis and degradation of lipid, ribonucleic acid (RNA) and protein in Pseudomonas aeruginosa were investigated. It was found that polymyxin B caused a marked degradation of the lipid fraction which was prelabeled with (3H-2)-glycerol. Thin-layer chromatographic analysis indicated that the main degraded lipids were phosphatidylethanolamine and phosphatidylglycerol, which constituted 80% and 15% of the total phospholipids of this organism, respectively. Polymyxin B also inhibited synthesis of RNA and protein in vivo. The severe inhibition of the uptake of labeled amino acids by polymyxin B indicated that the observed inhibition of RNA and protein synthesis possibly occurred at the level of substrate transports. The degradation of phospholipid might account for the defective membrane activities.", "contents": "Degradation of phospholipid in Pseudomonas aeruginosa induced by polymyxin B. Effects of polymyxin B on the synthesis and degradation of lipid, ribonucleic acid (RNA) and protein in Pseudomonas aeruginosa were investigated. It was found that polymyxin B caused a marked degradation of the lipid fraction which was prelabeled with (3H-2)-glycerol. Thin-layer chromatographic analysis indicated that the main degraded lipids were phosphatidylethanolamine and phosphatidylglycerol, which constituted 80% and 15% of the total phospholipids of this organism, respectively. Polymyxin B also inhibited synthesis of RNA and protein in vivo. The severe inhibition of the uptake of labeled amino acids by polymyxin B indicated that the observed inhibition of RNA and protein synthesis possibly occurred at the level of substrate transports. The degradation of phospholipid might account for the defective membrane activities."} {"id": "PMID:171249", "title": "Carbon monoxide-induced localized toxic anoxia in the rat brain cortex.", "content": "A new method has been developed for the determination of maximal reduction of NAD in the rat cerebral cortex. NADH fluorescence (450 nm) induced by 366-nm light and UV reflectance were measured by a time-sharing light pipe fluorometer. The redox state of the cortical surface was altered by perfusion of oxygen or carbon monoxide through a Teflon chamber adjacent to the dura. This study examines changes caused by local perfusion with the two gases in normoxia, hypoxia, and anoxia. Alternation of topical carbon monoxide and oxygen becomes effective in altering the intracellular redox state at 15% inspired oxygen and caused 20% changes at zero inspired oxygen. Conversely, topical application of oxygen to the systemically anoxic tissue causes oxidation of reduced NAPH in the cells within the field of fluorometric observation equivalent to that caused by breathing approximately 8% oxygen systemically.", "contents": "Carbon monoxide-induced localized toxic anoxia in the rat brain cortex. A new method has been developed for the determination of maximal reduction of NAD in the rat cerebral cortex. NADH fluorescence (450 nm) induced by 366-nm light and UV reflectance were measured by a time-sharing light pipe fluorometer. The redox state of the cortical surface was altered by perfusion of oxygen or carbon monoxide through a Teflon chamber adjacent to the dura. This study examines changes caused by local perfusion with the two gases in normoxia, hypoxia, and anoxia. Alternation of topical carbon monoxide and oxygen becomes effective in altering the intracellular redox state at 15% inspired oxygen and caused 20% changes at zero inspired oxygen. Conversely, topical application of oxygen to the systemically anoxic tissue causes oxidation of reduced NAPH in the cells within the field of fluorometric observation equivalent to that caused by breathing approximately 8% oxygen systemically."} {"id": "PMID:171251", "title": "Dicarboxylic acid transport in membrane vesicles from Bacillus subtilis.", "content": "Membrane vesicles isolated from Bacillus subtilis W23 catalyze active transport of the C4 dicarboxylic acids L-malate, fumarate, and succinate under aerobic conditions in the presence of the electron donor reduced beta-nicotinamide adenine dinucleotide or the non-physiological electron donor system ascorbate-phenazine methosulfate. The dicarboxylic acids are accumulated in unmodified form. Inhibitors of the respiratory chain, sulfhydryl reagents, and uncoupling agents inhibit the accumulation of the dicarboxylic acids. The affinity constants for transport of L-malate, fumarate, and succinate are 13.5, 7.5, and 4.3 muM, respectively; these values are severalfold lower than those reported previously for whole cells. Active transport of these dicarboxylic acids occurs via one highly specific transport system as is indicated by the following observations. (i) Each dicarboxylic acid inhibits the transport of the other two dicarboxylic acids competitively. (ii) The affinity constants determined for the inhibitory action are very similar to those determined for the transport process. (iii) Each dicarboxylic acid exchanges rapidly with a previously accumulated dicarboxylic acid. (iv) Other metabolically and structurally related compounds do not inhibit transport of these dicarboxylic acids significantly, except for L-aspartate and L-glutamate. However, transport of these dicarboxylic amino acids is mediated by independent system because membrane vesicles from B. subtilis 60346, lacking functional dicarboxylic amino acid transport activity, accumulate the C4 dicarboxylic acids at even higher rates than vesicles from B. subtilis W 23. (v) A constant ratio exists between the initial rates of transport of L-malate, fumarate, and succinate in all membrane vesicle preparations isolated from cells grown on various media. This high-affinity dicarboxylic acid transport system seems to be present constitutively in B. subtilis W23.", "contents": "Dicarboxylic acid transport in membrane vesicles from Bacillus subtilis. Membrane vesicles isolated from Bacillus subtilis W23 catalyze active transport of the C4 dicarboxylic acids L-malate, fumarate, and succinate under aerobic conditions in the presence of the electron donor reduced beta-nicotinamide adenine dinucleotide or the non-physiological electron donor system ascorbate-phenazine methosulfate. The dicarboxylic acids are accumulated in unmodified form. Inhibitors of the respiratory chain, sulfhydryl reagents, and uncoupling agents inhibit the accumulation of the dicarboxylic acids. The affinity constants for transport of L-malate, fumarate, and succinate are 13.5, 7.5, and 4.3 muM, respectively; these values are severalfold lower than those reported previously for whole cells. Active transport of these dicarboxylic acids occurs via one highly specific transport system as is indicated by the following observations. (i) Each dicarboxylic acid inhibits the transport of the other two dicarboxylic acids competitively. (ii) The affinity constants determined for the inhibitory action are very similar to those determined for the transport process. (iii) Each dicarboxylic acid exchanges rapidly with a previously accumulated dicarboxylic acid. (iv) Other metabolically and structurally related compounds do not inhibit transport of these dicarboxylic acids significantly, except for L-aspartate and L-glutamate. However, transport of these dicarboxylic amino acids is mediated by independent system because membrane vesicles from B. subtilis 60346, lacking functional dicarboxylic amino acid transport activity, accumulate the C4 dicarboxylic acids at even higher rates than vesicles from B. subtilis W 23. (v) A constant ratio exists between the initial rates of transport of L-malate, fumarate, and succinate in all membrane vesicle preparations isolated from cells grown on various media. This high-affinity dicarboxylic acid transport system seems to be present constitutively in B. subtilis W23."} {"id": "PMID:171252", "title": "Altered hexose transport and salt sensitivity in cyclic adenosine 3',5'-monophosphate-deficient Escherichia coli.", "content": "A cyclic adenosine 3',5'-monophosphate (cAMP)-deficient mutant strain of Escherichia coli K-12 was studied to determine the effect this cyclic nucleotide has on the overall growth and metabolism of this organism. Deficient cells were found to be more susceptible to growth inhibition by salts than were their cAMP-sufficient counterparts. The deficient cells transported alpha-methylglucoside by passive diffusion, whereas the parental cells or mutant cells grown in the presence of exogenous cAMP were able to take up alpha-methylglucoside by the normal active transport process. When viewed together with earlier studies conducted on cAMP-deficient cells, these findings support the view that cAMP plays a key role in regulating the construction and operation of the E. coli membrane system.", "contents": "Altered hexose transport and salt sensitivity in cyclic adenosine 3',5'-monophosphate-deficient Escherichia coli. A cyclic adenosine 3',5'-monophosphate (cAMP)-deficient mutant strain of Escherichia coli K-12 was studied to determine the effect this cyclic nucleotide has on the overall growth and metabolism of this organism. Deficient cells were found to be more susceptible to growth inhibition by salts than were their cAMP-sufficient counterparts. The deficient cells transported alpha-methylglucoside by passive diffusion, whereas the parental cells or mutant cells grown in the presence of exogenous cAMP were able to take up alpha-methylglucoside by the normal active transport process. When viewed together with earlier studies conducted on cAMP-deficient cells, these findings support the view that cAMP plays a key role in regulating the construction and operation of the E. coli membrane system."} {"id": "PMID:171253", "title": "Reduced nicotinamide adenine dinucleotide-activated phosphoenolpyruvate carboxylase in Pseudomonas MA: potential regulation between carbon assimilation and energy production.", "content": "Comparison of enzyme activities in crude extracts of methylamine-grown Pseudomonas MA (ATCC 23319) to those in succinate-grown cells indicates the involvement of an acetyl coenzyme A-independent phosphoenolpyruvate carboxylase in one-carbon metabolism. The purified phosphoenolpyruvate carboxylase is activated specifically by reduced nicotinamide adenine dinucleotide (KA = 0.2 mM). The regulatory properties of this enzyme suggests that phosphoenolpyruvate serves as a focal point for both carbon assimilation and energy metabolism.", "contents": "Reduced nicotinamide adenine dinucleotide-activated phosphoenolpyruvate carboxylase in Pseudomonas MA: potential regulation between carbon assimilation and energy production. Comparison of enzyme activities in crude extracts of methylamine-grown Pseudomonas MA (ATCC 23319) to those in succinate-grown cells indicates the involvement of an acetyl coenzyme A-independent phosphoenolpyruvate carboxylase in one-carbon metabolism. The purified phosphoenolpyruvate carboxylase is activated specifically by reduced nicotinamide adenine dinucleotide (KA = 0.2 mM). The regulatory properties of this enzyme suggests that phosphoenolpyruvate serves as a focal point for both carbon assimilation and energy metabolism."} {"id": "PMID:171254", "title": "Identification of an outer membrane protein of Escherichia coli, with a role in the coordination of deoxyribonucleic acid replication and cell elongation.", "content": "Protein G of molecular weight 15,000 is the fourth commonest protein in the outer membrane of Escherichia coli B/r. From experiments described here on the relationship of protein G production to cell elongation and septation, the hypothesis is proposed that protein G is a structural protein of cell elongation. Furthermore, a surplus of protein G is produced when deoxyribonucleic acid synthesis is arrested and septation is thereby prevented. Thus protein G may be an important coordination protein in E. coli for integration of deoxyribonucleic acid synthesis, cell envelope elongation, and septation. Inhibition of normal cell elongation in a rod configuration in E. coli B/r by the novel amidinopenicillanic acid FL1060 was accompanied by changes in the rate of appearance of protein G and several other outer membrane proteins. The rate of appearance of protein G decreased some 70% within 60 min, in parallel with termination of rounds of normal cell elongation. Filament-inducing concentrations of nalidixic acid increased dramatically the rate of appearance of protein G. After 30 min a plateau level some 250% higher than the control value was reached. Similar kinetics were observed in parallel with filament formation induced by incubation of a dnaB mutant of E. coli at the nonpermissive temperature. No change in the rate of appearance of protein G was observed during cephalexin- or benzylpenicillin-induced filament formation, indicating that increased protein G production was not a secondary consequence of filamentation. Cells treated with FL1060 lost their ability to be induced for protein G formation, with nalidixic acid, in parallel with their loss of ability to initiate rounds of normal cell elongation. A pulse-chase experiment demonstrated that the protein G appearing in the outer membrane as a consequence of inhibition of deoxyribonucleic acid synthesis was the result of de novo synthesis rather than of interconversion from previously synthesized protein species. A preliminary characterization of protein G revealed several similarities with the well-characterized lipoprotein of the outer membrane of E. coli. A comparison of the incorporation of several 14C-labeled amino acids into protein G and the lipoprotein revealed substantial differences, however, perhaps ruling out a simple relationship between these two proteins.", "contents": "Identification of an outer membrane protein of Escherichia coli, with a role in the coordination of deoxyribonucleic acid replication and cell elongation. Protein G of molecular weight 15,000 is the fourth commonest protein in the outer membrane of Escherichia coli B/r. From experiments described here on the relationship of protein G production to cell elongation and septation, the hypothesis is proposed that protein G is a structural protein of cell elongation. Furthermore, a surplus of protein G is produced when deoxyribonucleic acid synthesis is arrested and septation is thereby prevented. Thus protein G may be an important coordination protein in E. coli for integration of deoxyribonucleic acid synthesis, cell envelope elongation, and septation. Inhibition of normal cell elongation in a rod configuration in E. coli B/r by the novel amidinopenicillanic acid FL1060 was accompanied by changes in the rate of appearance of protein G and several other outer membrane proteins. The rate of appearance of protein G decreased some 70% within 60 min, in parallel with termination of rounds of normal cell elongation. Filament-inducing concentrations of nalidixic acid increased dramatically the rate of appearance of protein G. After 30 min a plateau level some 250% higher than the control value was reached. Similar kinetics were observed in parallel with filament formation induced by incubation of a dnaB mutant of E. coli at the nonpermissive temperature. No change in the rate of appearance of protein G was observed during cephalexin- or benzylpenicillin-induced filament formation, indicating that increased protein G production was not a secondary consequence of filamentation. Cells treated with FL1060 lost their ability to be induced for protein G formation, with nalidixic acid, in parallel with their loss of ability to initiate rounds of normal cell elongation. A pulse-chase experiment demonstrated that the protein G appearing in the outer membrane as a consequence of inhibition of deoxyribonucleic acid synthesis was the result of de novo synthesis rather than of interconversion from previously synthesized protein species. A preliminary characterization of protein G revealed several similarities with the well-characterized lipoprotein of the outer membrane of E. coli. A comparison of the incorporation of several 14C-labeled amino acids into protein G and the lipoprotein revealed substantial differences, however, perhaps ruling out a simple relationship between these two proteins."} {"id": "PMID:171255", "title": "Demonstration of acid phosphatase-containing vacuoles in hyphal tip cells of Sclerotium rolfsii.", "content": "A lysosomal system was demonstrated in hyphal tip cells of Sclerotium rolfsii by light and electron microscopy observations of the sites of acid phosphatase activity visualized by a modified Gomori lead nitrate method. The cytochemical reaction product was found to be present in numerous vacuoles, each aout 0.5 mum in diameter, which were seen as chains of spheres when viewed with the light microscope. They usually did not occur in the first 30 to 40 mum of the hyphal tip cell, but were concentrated in a zone extending from 30 to 200 mum from the hyphal apex. As shown by the electron microscope, the vacuoles were sometimes interconnected by narrow channels. Acid phosphatase reaction product was also occasionally localized in vacuoles of the older hyphal cells, but never in apical vesicles, lipid bodies, or microbodies. It is proposed that this vacuolar system may orginate from the endoplasmic reticulum.", "contents": "Demonstration of acid phosphatase-containing vacuoles in hyphal tip cells of Sclerotium rolfsii. A lysosomal system was demonstrated in hyphal tip cells of Sclerotium rolfsii by light and electron microscopy observations of the sites of acid phosphatase activity visualized by a modified Gomori lead nitrate method. The cytochemical reaction product was found to be present in numerous vacuoles, each aout 0.5 mum in diameter, which were seen as chains of spheres when viewed with the light microscope. They usually did not occur in the first 30 to 40 mum of the hyphal tip cell, but were concentrated in a zone extending from 30 to 200 mum from the hyphal apex. As shown by the electron microscope, the vacuoles were sometimes interconnected by narrow channels. Acid phosphatase reaction product was also occasionally localized in vacuoles of the older hyphal cells, but never in apical vesicles, lipid bodies, or microbodies. It is proposed that this vacuolar system may orginate from the endoplasmic reticulum."} {"id": "PMID:171256", "title": "Assembly of the mitochondrial membrane system. Cytoplasmic mutants of Saccharomyces cerevisiae with lesions in enzymes of the respiratory chain and in the mitochondrial ATPase.", "content": "Mutants of Saccharomyces cervisiae with defects in enzymes of the electron transfer chain and in the rutamycin-sensitive ATPase have been isolated. Some of the mutants are specifically affected in either cytochrome oxidase, coenzyme QH2-cytochrome c reductase or ATPase. Other strains are deficient in both cytochrome oxidase and coenzyme QH2-cytochrome c reductase but still have rutamycin-sensitive ATPase. All the mutants reported in this study fail to be complemented by a rho0 tester derived from a respiratory competent strain. The meiotic spore progeny obtained by mating the mutants to a respiratory competent haploid yeast, when scored for growth on glycerol, show a non-Mendelian segregation of the phenotype. These two genetic tests indicate the mutations to be cytoplasmically inherited.", "contents": "Assembly of the mitochondrial membrane system. Cytoplasmic mutants of Saccharomyces cerevisiae with lesions in enzymes of the respiratory chain and in the mitochondrial ATPase. Mutants of Saccharomyces cervisiae with defects in enzymes of the electron transfer chain and in the rutamycin-sensitive ATPase have been isolated. Some of the mutants are specifically affected in either cytochrome oxidase, coenzyme QH2-cytochrome c reductase or ATPase. Other strains are deficient in both cytochrome oxidase and coenzyme QH2-cytochrome c reductase but still have rutamycin-sensitive ATPase. All the mutants reported in this study fail to be complemented by a rho0 tester derived from a respiratory competent strain. The meiotic spore progeny obtained by mating the mutants to a respiratory competent haploid yeast, when scored for growth on glycerol, show a non-Mendelian segregation of the phenotype. These two genetic tests indicate the mutations to be cytoplasmically inherited."} {"id": "PMID:171257", "title": "Insulin-induced reduction of membrane receptor concentrations in isolated fat cells and lymphocytes. Independence from receptor occupation and possible relation to proteolytic activity of insulin.", "content": "Incubation of cultured human lymphocytes or isolated rat fat cells at 37 degrees with insulin results in a time-dependent fall in the ability of the thoroughly washed cells to bind 125I-labeled insulin. Although this effect is dependent on the concentration of insulin used in the preincubation period, the concentration dependence pattern varies directly with the length of this incubation, and kinetically (i.e. at early times) it is virtually impossible to demonstrate saturability with respect to insulin concentration. Significant effects are demonstrable at very early times (e.g. 1 to 3 hours) provided sufficiently high insulin concentration (i.e. 5 mug/ml or more) are used...", "contents": "Insulin-induced reduction of membrane receptor concentrations in isolated fat cells and lymphocytes. Independence from receptor occupation and possible relation to proteolytic activity of insulin. Incubation of cultured human lymphocytes or isolated rat fat cells at 37 degrees with insulin results in a time-dependent fall in the ability of the thoroughly washed cells to bind 125I-labeled insulin. Although this effect is dependent on the concentration of insulin used in the preincubation period, the concentration dependence pattern varies directly with the length of this incubation, and kinetically (i.e. at early times) it is virtually impossible to demonstrate saturability with respect to insulin concentration. Significant effects are demonstrable at very early times (e.g. 1 to 3 hours) provided sufficiently high insulin concentration (i.e. 5 mug/ml or more) are used..."} {"id": "PMID:171258", "title": "Structural analyses of mammalian ribosomal ribonucleic acid and its precursors. Nucleotide sequence of ribosomal 5.8 S ribonucleic acid.", "content": "The nucleotide sequence of ribosomal 5.8 S RNA (also known as 7 S or 5.5 S rRNA) from Novikoff hepatoma ascites cells has been determined to be (see article). Estimations of the secondary structure based upon maximized base pairing and the fragments of partial ribonuclease digestion indicate that there may be five base-paired regions in the molecule, three forming a folding of the termini and two forming secondary hairpin loops. The sequence of Novikoff hepatoma 5.8 S rRNA is about 75% homologous with that of yeast 5.8 S rRNA (Rubin, G.M. (1973) J. Biol. Chem. 248, 3860-3875) and similar models for secondary structure are proposed. Both models contain a very stable G-C rich hairpin loop (residues 116 to 138), a less stable A-U-rich hairpin loop (residues 64 to 91) and two symmetrical bulges (residues 15 to 25 and 40 to 44).", "contents": "Structural analyses of mammalian ribosomal ribonucleic acid and its precursors. Nucleotide sequence of ribosomal 5.8 S ribonucleic acid. The nucleotide sequence of ribosomal 5.8 S RNA (also known as 7 S or 5.5 S rRNA) from Novikoff hepatoma ascites cells has been determined to be (see article). Estimations of the secondary structure based upon maximized base pairing and the fragments of partial ribonuclease digestion indicate that there may be five base-paired regions in the molecule, three forming a folding of the termini and two forming secondary hairpin loops. The sequence of Novikoff hepatoma 5.8 S rRNA is about 75% homologous with that of yeast 5.8 S rRNA (Rubin, G.M. (1973) J. Biol. Chem. 248, 3860-3875) and similar models for secondary structure are proposed. Both models contain a very stable G-C rich hairpin loop (residues 116 to 138), a less stable A-U-rich hairpin loop (residues 64 to 91) and two symmetrical bulges (residues 15 to 25 and 40 to 44)."} {"id": "PMID:171259", "title": "Arrangement of the subunits in solubilized and membrane-bound cytochrome c oxidase from bovine heart.", "content": "The arrangement of the six cytochrome c oxidase subunits in the inner membrane of bovine heart mitochondria was investigated. The experiments were carried out in three steps. In the first step, exposed subunits were coupled to the membrane-impermeant reagent p-diazonium benzene [32S]sulfonate. In the second step, the membranes were lysed with cholate anc cytochrome c oxidase was isolated by immunoprecipitation. In the third step, the six cytochrome c oxidase subunits were separated from each other by dodecyl sulfate-acrylamide gel electrophoresis and scanned for radioactivity. Exposed subunits on the outer side of the mitochondrial inner membrane were identified by labeling intact mitochondria. Exposed subunits on the matrix side of the inner membrane were identified by labeling sonically prepared submitochondrial particles in which the matrix side of the inner membrane is exposed to the suspending medium. Since sonic irradiation leads to a rearrangement of cytochrome c oxidase in a large fraction of the resulting submitochondrial particles, an immunochemical procedure was developed for isolating particles with a low content of displaced cytochrome c oxidase. With mitochondria, subunits II, V, and VI were labeled, whereas in purified submitochondrial particles most of the label was in subunit III. The arrangement of cytochrome c oxidase in the mitochondrial inner membrane is thus transmembraneous and asymmetric; subunits II, V, and VI are situated on the outer side, subunit III is situated on the matrix side, and subunits I and IV are buried in the interior of the membrane. In a study of purified cytochrome c oxidase labeled with p-diazonium benzene [32S]sulfonate, the results were similar to those obtained with the membrane-bound enzyme. Subunits I and IV were inaccessible to the reagent, whereas the other four subunits were accessible. In contrast, all six subunits became labeled if the enzyme was dissociated with dodecyl sulfate before being exposed to the labeling reagent.", "contents": "Arrangement of the subunits in solubilized and membrane-bound cytochrome c oxidase from bovine heart. The arrangement of the six cytochrome c oxidase subunits in the inner membrane of bovine heart mitochondria was investigated. The experiments were carried out in three steps. In the first step, exposed subunits were coupled to the membrane-impermeant reagent p-diazonium benzene [32S]sulfonate. In the second step, the membranes were lysed with cholate anc cytochrome c oxidase was isolated by immunoprecipitation. In the third step, the six cytochrome c oxidase subunits were separated from each other by dodecyl sulfate-acrylamide gel electrophoresis and scanned for radioactivity. Exposed subunits on the outer side of the mitochondrial inner membrane were identified by labeling intact mitochondria. Exposed subunits on the matrix side of the inner membrane were identified by labeling sonically prepared submitochondrial particles in which the matrix side of the inner membrane is exposed to the suspending medium. Since sonic irradiation leads to a rearrangement of cytochrome c oxidase in a large fraction of the resulting submitochondrial particles, an immunochemical procedure was developed for isolating particles with a low content of displaced cytochrome c oxidase. With mitochondria, subunits II, V, and VI were labeled, whereas in purified submitochondrial particles most of the label was in subunit III. The arrangement of cytochrome c oxidase in the mitochondrial inner membrane is thus transmembraneous and asymmetric; subunits II, V, and VI are situated on the outer side, subunit III is situated on the matrix side, and subunits I and IV are buried in the interior of the membrane. In a study of purified cytochrome c oxidase labeled with p-diazonium benzene [32S]sulfonate, the results were similar to those obtained with the membrane-bound enzyme. Subunits I and IV were inaccessible to the reagent, whereas the other four subunits were accessible. In contrast, all six subunits became labeled if the enzyme was dissociated with dodecyl sulfate before being exposed to the labeling reagent."} {"id": "PMID:171260", "title": "Interaction of human plasma low density lipoprotein with concanavalin A and with ricin.", "content": "Native human plasma low density lipoprotein (LDL) interacts with concanavalin A but not with ricin; apOLDL reacts with both lectins. Each reaction is inhibited by the appropriate lectin-specific carbohydrate. The \"receptors\" on LDL for these two lectins are not destroyed by digestion by proteolytic enzymes. Peptide hydrolysis does not influence the reactivity of LDL toward concanavalin A. It does, however, substantially enhance the ability of the lipoprotein to interact with ricin. The data strongly suggest that the carbohydrate protion of a glycoprotein component of LDL is bound at the saccharidespecific active site on the lectin.", "contents": "Interaction of human plasma low density lipoprotein with concanavalin A and with ricin. Native human plasma low density lipoprotein (LDL) interacts with concanavalin A but not with ricin; apOLDL reacts with both lectins. Each reaction is inhibited by the appropriate lectin-specific carbohydrate. The \"receptors\" on LDL for these two lectins are not destroyed by digestion by proteolytic enzymes. Peptide hydrolysis does not influence the reactivity of LDL toward concanavalin A. It does, however, substantially enhance the ability of the lipoprotein to interact with ricin. The data strongly suggest that the carbohydrate protion of a glycoprotein component of LDL is bound at the saccharidespecific active site on the lectin."} {"id": "PMID:171261", "title": "Isolation and characterization of a pyrophosphate-dependent phosphofructokinase from Propionibacterium shermanii.", "content": "A pyrophosphate-dependent phosphofructokinase (pyrophosphate; D-fructose-6-phosphate-1-phosphotransferase) has been purified and characterized from extracts of Propionibacterium shermanii. The enzyme catalyzes the transfer of phosphate from pyrophosphate to fructose 6-phosphate to yield fructose-1,6-P2 and phosphate. This unique enzymatic activity was observed initially in Entamoeba histolytica (Reeves, R.E., South, D.J., Blytt, H.G., and Warren, L. G. (1974) J. Biol. Chem. 249, 7734-7741). This is the third pyrophosphate-utilizing enzyme that these two diverse organisms have in common. The others are phosphoenolpyruvate carboxytransphosphorylase and pyruvate phosphate dikinase. The PPi-phosphofructokinase from P. shermanii is specific for fructose-6-P and fructose-1,6-P2, no other phosphorylated sugars were utilized. Phosphate could be replaced by arsenate. The Km values are: phosphate, 6.0 X 10(-4) M; fructose-1, 6-P2, 5.1 X 10(-5) M; pyrophosphate, 6.9 X 10(-5) M; and fructose-6-P, 1.0 X 10(-4) M. The S20w is 5.1 S. The molecular weight of the native enzyme is 95,000. Sodium dodecyl sulfate electrophoresis of the enzyme showed a single band migrating with an Rf corresponding to a molecular weight of 48,000. Extracts of P. shermanii have PPi-phosphofructokinase activity approximately 6 times greater than ATP-phosphofructokinase and 15 to 20 times greater than fructose diphosphatase activities. It is proposed that (a) PPi may replace ATP in the formation of fructose-1-6-P2 when the organism is grown on glucose and (b) when the organism is grown on lactate or glycerol the conversion of fructose-1,6-P2 to fructose-6-P during gluconeogenesis may occur by phosphorolysis rather than hydrolysis.", "contents": "Isolation and characterization of a pyrophosphate-dependent phosphofructokinase from Propionibacterium shermanii. A pyrophosphate-dependent phosphofructokinase (pyrophosphate; D-fructose-6-phosphate-1-phosphotransferase) has been purified and characterized from extracts of Propionibacterium shermanii. The enzyme catalyzes the transfer of phosphate from pyrophosphate to fructose 6-phosphate to yield fructose-1,6-P2 and phosphate. This unique enzymatic activity was observed initially in Entamoeba histolytica (Reeves, R.E., South, D.J., Blytt, H.G., and Warren, L. G. (1974) J. Biol. Chem. 249, 7734-7741). This is the third pyrophosphate-utilizing enzyme that these two diverse organisms have in common. The others are phosphoenolpyruvate carboxytransphosphorylase and pyruvate phosphate dikinase. The PPi-phosphofructokinase from P. shermanii is specific for fructose-6-P and fructose-1,6-P2, no other phosphorylated sugars were utilized. Phosphate could be replaced by arsenate. The Km values are: phosphate, 6.0 X 10(-4) M; fructose-1, 6-P2, 5.1 X 10(-5) M; pyrophosphate, 6.9 X 10(-5) M; and fructose-6-P, 1.0 X 10(-4) M. The S20w is 5.1 S. The molecular weight of the native enzyme is 95,000. Sodium dodecyl sulfate electrophoresis of the enzyme showed a single band migrating with an Rf corresponding to a molecular weight of 48,000. Extracts of P. shermanii have PPi-phosphofructokinase activity approximately 6 times greater than ATP-phosphofructokinase and 15 to 20 times greater than fructose diphosphatase activities. It is proposed that (a) PPi may replace ATP in the formation of fructose-1-6-P2 when the organism is grown on glucose and (b) when the organism is grown on lactate or glycerol the conversion of fructose-1,6-P2 to fructose-6-P during gluconeogenesis may occur by phosphorolysis rather than hydrolysis."} {"id": "PMID:171262", "title": "Steroid-protein interactions. Stopped flow fluorescence studies of the interaction between steroid hormones and progesterone-binding globulin.", "content": "Stopped flow fluorometry, measuring changes in the intrinsic fluorescence of progesterone-binding globulin (PBG), was used to determine the association and dissociation rates of the interaction of PBG with seven delta4-3-ketosteroids. The rates of formation and dissociation of the PBG-progesterone complex were measured as a function of concentration and temperature. At 20 degrees, kon = 8.7 X 10(7) M-1 S-1 and koff = 0.060 S-1. The association rate constants for progesterone, deoxycorticosterone, testosterone, testosterone acetate, and medrogestone were found to be the same within experimental error. The different affinities of PBG for these steroids result from the dissociation rate constants of the steroids which ranged from 0.43 S-1 for testosterone to 0.024 S-1 for medrogestone. Two corticosteroids, corticosterone and cortisol, were both bound somewhat more slowly (approximately 5 X 10(7) M-1 S-1). Reflecting their very low affinity for PBG both steroids dissociate very rapidly: corticosterone at 1.4 S-1 and cortisol at 90 S-1. The ratio of association to dissociation rate constants gave affinity constants in agreement with independently determined constants.", "contents": "Steroid-protein interactions. Stopped flow fluorescence studies of the interaction between steroid hormones and progesterone-binding globulin. Stopped flow fluorometry, measuring changes in the intrinsic fluorescence of progesterone-binding globulin (PBG), was used to determine the association and dissociation rates of the interaction of PBG with seven delta4-3-ketosteroids. The rates of formation and dissociation of the PBG-progesterone complex were measured as a function of concentration and temperature. At 20 degrees, kon = 8.7 X 10(7) M-1 S-1 and koff = 0.060 S-1. The association rate constants for progesterone, deoxycorticosterone, testosterone, testosterone acetate, and medrogestone were found to be the same within experimental error. The different affinities of PBG for these steroids result from the dissociation rate constants of the steroids which ranged from 0.43 S-1 for testosterone to 0.024 S-1 for medrogestone. Two corticosteroids, corticosterone and cortisol, were both bound somewhat more slowly (approximately 5 X 10(7) M-1 S-1). Reflecting their very low affinity for PBG both steroids dissociate very rapidly: corticosterone at 1.4 S-1 and cortisol at 90 S-1. The ratio of association to dissociation rate constants gave affinity constants in agreement with independently determined constants."} {"id": "PMID:171263", "title": "Mechanism of action of uridine diphosphoglucose dehydrogenase. Evidence for a second reversible dehydrogenation step involving an essential thiol group.", "content": "Although the enzyme UDP-glucose dehydrogenase from beef liver (E.C. 1.1.1.22) is known to abstract the pro-R hydrogen stereospecifically at carbon 6 of the glucose moiety of the substrate by a reversible step in converting UDP-glucose to UDP-alpha-D-gluco-hexodialdose (UDP-Glc-6-CHO), prolonged incubation of the enzyme with UDP-glucose and tritium-labeled NADH, under conditions favoring hydrogen exchange between the two, results in equivalent labeling of both hydrogens at carbon 6. This shows that the pro-S hydrogen at carbon 6 is also abstracted by a reversible process which must then involve a derivative of the carboxyl group of UDP-glucuronic acid (UDP-GlcUA) that is capable of reversible hydrogenation-dehydrogenation. It is the hydrolysis of this derivative that accounts for the well known irreversibility of the overall reaction. Derivatization of the enzyme's essential thiol group with 5,5'-dithiobis-(2-nitrobenzoate) eliminates the ability of the enzyme to either oxidize or reduce UDP-Glc-6-CHO. Replacement of the 5-thio-2-nitrobenzoate group with cyanide fully restores the enzyme's capacity to reduce UDP-Glc-6-CHO but has no effect on the inhibition of the oxidation to UDP-GlcUA. This indicates that the essential thiol group is involved in the second reversible dehydrogenation step and serves to form a thiol ester with the carboxyl of the product, UDP-GlcUA. It is suggested that thiol ester intermediates are a general characteristic of all 4-electron NAD-linked dehydrogenase reactions.", "contents": "Mechanism of action of uridine diphosphoglucose dehydrogenase. Evidence for a second reversible dehydrogenation step involving an essential thiol group. Although the enzyme UDP-glucose dehydrogenase from beef liver (E.C. 1.1.1.22) is known to abstract the pro-R hydrogen stereospecifically at carbon 6 of the glucose moiety of the substrate by a reversible step in converting UDP-glucose to UDP-alpha-D-gluco-hexodialdose (UDP-Glc-6-CHO), prolonged incubation of the enzyme with UDP-glucose and tritium-labeled NADH, under conditions favoring hydrogen exchange between the two, results in equivalent labeling of both hydrogens at carbon 6. This shows that the pro-S hydrogen at carbon 6 is also abstracted by a reversible process which must then involve a derivative of the carboxyl group of UDP-glucuronic acid (UDP-GlcUA) that is capable of reversible hydrogenation-dehydrogenation. It is the hydrolysis of this derivative that accounts for the well known irreversibility of the overall reaction. Derivatization of the enzyme's essential thiol group with 5,5'-dithiobis-(2-nitrobenzoate) eliminates the ability of the enzyme to either oxidize or reduce UDP-Glc-6-CHO. Replacement of the 5-thio-2-nitrobenzoate group with cyanide fully restores the enzyme's capacity to reduce UDP-Glc-6-CHO but has no effect on the inhibition of the oxidation to UDP-GlcUA. This indicates that the essential thiol group is involved in the second reversible dehydrogenation step and serves to form a thiol ester with the carboxyl of the product, UDP-GlcUA. It is suggested that thiol ester intermediates are a general characteristic of all 4-electron NAD-linked dehydrogenase reactions."} {"id": "PMID:171264", "title": "Identification of an essential lysine in porcine heart mitochondrial malate dehydrogenase.", "content": "The reversible inactivation of porcine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate yields an irreversible modification upon sodium borohydride reduction. A 200-fold molar excess of pyridoxal-5'-P over enzyme results in inactivation to the extent of 54%, and incorporation of 5.7 mol of inactivator per mol of enzyme. The same inactivation carried out in the presence of 80 mM coenzyme, NADH, produces malate dehydrogenase which is approximately 94% active and contains 4.6 mol of pyridoxal-5'-P per mol of enzyme. The incorporation difference between inactivated and protected samples suggests, for total inactivation, the modification of 2 residues per mol of enzyme (i.e. 1 residue per subunit, or 1 per enzymatic active site). This specificity was confirmed by the isolation of a single pyridoxyl-5'-P-labeled \"difference peptide\" obtained by comparison of the Dowex 1-X2 elution profiles of tryptic digests of protected and inactivated samples, respectively. Amino acid analysis of the peptide demonstrated the presence of N6-pyridoxyl-L-lysine (Lys(Pyx)), establishing the existence of an essential lysing residue in the active center of malate dehydrogenase. The amino acid sequence of the active center hexapeptide has been determined to be: H2NLys(Pyx)Pro-Gly-Met-Thr-Arg-COOH.", "contents": "Identification of an essential lysine in porcine heart mitochondrial malate dehydrogenase. The reversible inactivation of porcine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate yields an irreversible modification upon sodium borohydride reduction. A 200-fold molar excess of pyridoxal-5'-P over enzyme results in inactivation to the extent of 54%, and incorporation of 5.7 mol of inactivator per mol of enzyme. The same inactivation carried out in the presence of 80 mM coenzyme, NADH, produces malate dehydrogenase which is approximately 94% active and contains 4.6 mol of pyridoxal-5'-P per mol of enzyme. The incorporation difference between inactivated and protected samples suggests, for total inactivation, the modification of 2 residues per mol of enzyme (i.e. 1 residue per subunit, or 1 per enzymatic active site). This specificity was confirmed by the isolation of a single pyridoxyl-5'-P-labeled \"difference peptide\" obtained by comparison of the Dowex 1-X2 elution profiles of tryptic digests of protected and inactivated samples, respectively. Amino acid analysis of the peptide demonstrated the presence of N6-pyridoxyl-L-lysine (Lys(Pyx)), establishing the existence of an essential lysing residue in the active center of malate dehydrogenase. The amino acid sequence of the active center hexapeptide has been determined to be: H2NLys(Pyx)Pro-Gly-Met-Thr-Arg-COOH."} {"id": "PMID:171265", "title": "Studies on the mechanism of adenosylcobalamin-dependent ribonucleotide reduction by the use of analogs of the coenzyme.", "content": "A series of 17 analogs of 5'-deoxy-5'-adenosylcobalamin(adenosylcobalamin) have been synthesized with modifications in the base or ribose moiety of the nucleoside ligand. These analogs have been examined for their effects on reactions catalyzed by the ribonucleotide reductase of Lactobacillus leichmannii. All the analogs are inhibitors of ATP reduction in the presence of adenosylcobalamin as coenzyme, and hence all are bound to the catalytic site. Only the 3-beta-D-ribofuranosyladenine analog (isoadenosylcobalamin) showed substantial activity as a coenzyme in ATP reduction, giving a rate of 59% of that obtained with the adenosylcobalamin. Lesser rates of reduction were obtained with nebularyl-, 2'-deoxyadenosyl-, tubercidyl-, isopropylideneadenosyl-, L-adenosyl-, and ara-adenosylcobalamin, coenzyme activity decreasing in that order. Other analogs showed no significant coenzyme activity. The rate of hydrogen exchange into water from the 5'-methylene group of the nucleoside ligand appeared to parallel the coenzyme activity in those analogs examined, but only the four cobalamins with highest coenzyme activity (adenosyl, isoadenosyl, nebularyl, 2'-deoxyadenosyl) gave detectable amounts of \"active coenzyme B12,\" THe rapidly formed paramagnetic intermediate of ribonucleotide reduction. The enzyme system produced the slowly formed paramagnetic species characterized by a doublet EPR spectrum only with adenosyl- and isoadenosylcobalamin. By contrast the enzymic degradation of analogs to cob(II)alamin and 5'-deoxynucleoside occurred not only with those analogs active as coenzymes and in the exchange reaction but also with a number of coenzymically inactive analogs, and the rate of degradation was unrelated to the rate of ribonucleotide reduction for those analogs with coenzyme activity.", "contents": "Studies on the mechanism of adenosylcobalamin-dependent ribonucleotide reduction by the use of analogs of the coenzyme. A series of 17 analogs of 5'-deoxy-5'-adenosylcobalamin(adenosylcobalamin) have been synthesized with modifications in the base or ribose moiety of the nucleoside ligand. These analogs have been examined for their effects on reactions catalyzed by the ribonucleotide reductase of Lactobacillus leichmannii. All the analogs are inhibitors of ATP reduction in the presence of adenosylcobalamin as coenzyme, and hence all are bound to the catalytic site. Only the 3-beta-D-ribofuranosyladenine analog (isoadenosylcobalamin) showed substantial activity as a coenzyme in ATP reduction, giving a rate of 59% of that obtained with the adenosylcobalamin. Lesser rates of reduction were obtained with nebularyl-, 2'-deoxyadenosyl-, tubercidyl-, isopropylideneadenosyl-, L-adenosyl-, and ara-adenosylcobalamin, coenzyme activity decreasing in that order. Other analogs showed no significant coenzyme activity. The rate of hydrogen exchange into water from the 5'-methylene group of the nucleoside ligand appeared to parallel the coenzyme activity in those analogs examined, but only the four cobalamins with highest coenzyme activity (adenosyl, isoadenosyl, nebularyl, 2'-deoxyadenosyl) gave detectable amounts of \"active coenzyme B12,\" THe rapidly formed paramagnetic intermediate of ribonucleotide reduction. The enzyme system produced the slowly formed paramagnetic species characterized by a doublet EPR spectrum only with adenosyl- and isoadenosylcobalamin. By contrast the enzymic degradation of analogs to cob(II)alamin and 5'-deoxynucleoside occurred not only with those analogs active as coenzymes and in the exchange reaction but also with a number of coenzymically inactive analogs, and the rate of degradation was unrelated to the rate of ribonucleotide reduction for those analogs with coenzyme activity."} {"id": "PMID:171266", "title": "Superoxide, hydrogen peroxide, and singlet oxygen in lipid peroxidation by a xanthine oxidase system.", "content": "1. Xanthine oxidase acting aerobically upon acetaldehyde was found to cause the peroxidation of linolenate. This was demonstrated by increased absorbance at 233 nm due to diene conjugation and by the detection of a lipid peroxide spot on the thin layer chromatograms. 2. Superoxide dismutase inhibited this lipid peroxidation, as did catalase, thus indicating that both O2- and H2O2 were essential intermediates. Scavengers of singlet oxygen also inhibited the peroxidation of linolenate, whereas scavengers of hydroxyl radical did not. These effects, which were observed in the absence of iron salts, led to the proposal that O2- and H2O2 can directly give rise to a singlet oxygen, as follows: O2- + H2O2 leads to OH- + OH. + O2. 3. This proposal was further supported through the use of 2,5-dimethylfuran, as an indicating scavenger of singlet oxygen. Thus, when this compound was exposed to a known source of singlet oxygen, it gave a product which was detectable by thin layer chromatography. This product was also observed when 2,5-dimethylfuran was exposed to the xanthine oxidase system, in which case its accumulation was prevented by superoxide dismutase or by catalase, but not by scavengers of hydroxyl radical.", "contents": "Superoxide, hydrogen peroxide, and singlet oxygen in lipid peroxidation by a xanthine oxidase system. 1. Xanthine oxidase acting aerobically upon acetaldehyde was found to cause the peroxidation of linolenate. This was demonstrated by increased absorbance at 233 nm due to diene conjugation and by the detection of a lipid peroxide spot on the thin layer chromatograms. 2. Superoxide dismutase inhibited this lipid peroxidation, as did catalase, thus indicating that both O2- and H2O2 were essential intermediates. Scavengers of singlet oxygen also inhibited the peroxidation of linolenate, whereas scavengers of hydroxyl radical did not. These effects, which were observed in the absence of iron salts, led to the proposal that O2- and H2O2 can directly give rise to a singlet oxygen, as follows: O2- + H2O2 leads to OH- + OH. + O2. 3. This proposal was further supported through the use of 2,5-dimethylfuran, as an indicating scavenger of singlet oxygen. Thus, when this compound was exposed to a known source of singlet oxygen, it gave a product which was detectable by thin layer chromatography. This product was also observed when 2,5-dimethylfuran was exposed to the xanthine oxidase system, in which case its accumulation was prevented by superoxide dismutase or by catalase, but not by scavengers of hydroxyl radical."} {"id": "PMID:171267", "title": "Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate and testosterone production in isolated Leydig cells.", "content": "Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) formation and testosterone synthesis were studied in collagenase-dispersed interstitial cells from the adult rat testis. Binding of 125I-human chorionic gonadotropin (hCG) by isolated Leydig cells was of high affinity (Ka = 10(10) M-1) and low capacity, equivalent to approximately 6000 sites/cell. The binding data were consistent with the presence of a single order of receptors, with no interaction between binding sites. Stimulation of testosterone synthesis by increasing concentrations of hCG was completely dissociated from changes in cyclic AMP formation, and maximum activation of steroidogenesis was induced by hCG concentrations which had no effect upon cyclic AMP production. Kinetic analysis of gonadotropin-induced responses in dispersed Leydig cells also showed a marked dissociation between steroidogenesis and cyclic nucleotide formation. Low concentrations of hCG caused maximum stimulation of testosterone production which was not accompanied by a rise in cyclic AMP formation at any time after addition of gonadotropin. Higher concentrations of hCG caused marked elevations of cyclic AMP at progressively earlier time intervals, but did not alter the 20 to 30 min lag period required for induction of testosterone synthesis. These observations indicated that occupancy of gonadotropin receptors occurs over a much wider range of hCG concentration than that required for maximum steroidogenesis.", "contents": "Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate and testosterone production in isolated Leydig cells. Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) formation and testosterone synthesis were studied in collagenase-dispersed interstitial cells from the adult rat testis. Binding of 125I-human chorionic gonadotropin (hCG) by isolated Leydig cells was of high affinity (Ka = 10(10) M-1) and low capacity, equivalent to approximately 6000 sites/cell. The binding data were consistent with the presence of a single order of receptors, with no interaction between binding sites. Stimulation of testosterone synthesis by increasing concentrations of hCG was completely dissociated from changes in cyclic AMP formation, and maximum activation of steroidogenesis was induced by hCG concentrations which had no effect upon cyclic AMP production. Kinetic analysis of gonadotropin-induced responses in dispersed Leydig cells also showed a marked dissociation between steroidogenesis and cyclic nucleotide formation. Low concentrations of hCG caused maximum stimulation of testosterone production which was not accompanied by a rise in cyclic AMP formation at any time after addition of gonadotropin. Higher concentrations of hCG caused marked elevations of cyclic AMP at progressively earlier time intervals, but did not alter the 20 to 30 min lag period required for induction of testosterone synthesis. These observations indicated that occupancy of gonadotropin receptors occurs over a much wider range of hCG concentration than that required for maximum steroidogenesis."} {"id": "PMID:171268", "title": "Specificity of the S1 nuclease from Aspergillus oryzae.", "content": "Conditions are described for digesting single-stranded DNA by S1 nuclease without introducing breaks in double-stranded DNA. The enzyme is inhibited by low concentrations of various compounds of phosphate. Under certain conditions S1 nuclease cleaves the strand opposite a nick in bacteriophage T5 DNA; under other conditions, the enzyme cleaves a loop in one strand of heteroduplex lambdaDNA while leaving the opposite strand intact. S1 nuclease makes many single strand breaks in ultraviolet-irradiated duplex lambdaDNA. Superhelical DNA of phiX174 (Form I) is converted first to a relaxed circular molecule (Form II), and then to a linear molecule (Form III) by cleavage at one site per molecule. Since the cleavage occurs at many sites in the population of molecules, the partially single-stranded regions in phiX174 superhelical DNA are not determined by specific nucleotide sequences.", "contents": "Specificity of the S1 nuclease from Aspergillus oryzae. Conditions are described for digesting single-stranded DNA by S1 nuclease without introducing breaks in double-stranded DNA. The enzyme is inhibited by low concentrations of various compounds of phosphate. Under certain conditions S1 nuclease cleaves the strand opposite a nick in bacteriophage T5 DNA; under other conditions, the enzyme cleaves a loop in one strand of heteroduplex lambdaDNA while leaving the opposite strand intact. S1 nuclease makes many single strand breaks in ultraviolet-irradiated duplex lambdaDNA. Superhelical DNA of phiX174 (Form I) is converted first to a relaxed circular molecule (Form II), and then to a linear molecule (Form III) by cleavage at one site per molecule. Since the cleavage occurs at many sites in the population of molecules, the partially single-stranded regions in phiX174 superhelical DNA are not determined by specific nucleotide sequences."} {"id": "PMID:171269", "title": "Stimulation of adenylate cyclase from isolated hepatocytes and Kupffer cells.", "content": "Hepatocytes and Kupffer cells were separated from rat liver after prelabeling the Kupffer cells with colloidal iron and perfusion of the liver with digestive enzymes. The activity of several enzymes from Kupffer cells and hepatocytes was compared to validate this method of cell separation. The ratios of hepatocyte to Kupffer cell specific activities of glucose-6-phosphatase, 5'-nucleotidase, adenylate cyclase, and acid phosphatase were 20, 0.39, 0.18, and 0.078, respectively. Adenylate cyclases from hepatocytes and Kupffer cells were stimulated by fluoride ion, GTP, and catecholamines. Hepatocyte adenylate cyclase was also stimulated by glucagon, secretin, vasoactive intestinal polypeptide, and by prostaglandin E1, whereas, the Kupffer cell enzyme was completely insensitive to these hormones. The stimulation of hepatocyte adenylate cyclase by combinations of glucagon plus secretin, or glucagon plus vasoactive intestinal polypeptide, were equivalent to the sum of the individual stimulations. This suggests that the hepatocyte has specific receptors for glucagon and for vasoactive intestinal polypeptide and secretin. Prostaglandin E1 stimulation of hepatocyte adenylate cyclase was not additive to the stimulation caused by polypeptide hormones or catecholamines, nor did prostaglandin E1 decrease stimulation caused by these hormones. Although prostaglandin-sensitive adenylate cyclase was recovered with hepatocytes, 40 to 50% of the total liver prostaglandin-sensitive activity was recovered in a fraction of cell debris mixed with small cells which did not phagocytize colloidal iron.", "contents": "Stimulation of adenylate cyclase from isolated hepatocytes and Kupffer cells. Hepatocytes and Kupffer cells were separated from rat liver after prelabeling the Kupffer cells with colloidal iron and perfusion of the liver with digestive enzymes. The activity of several enzymes from Kupffer cells and hepatocytes was compared to validate this method of cell separation. The ratios of hepatocyte to Kupffer cell specific activities of glucose-6-phosphatase, 5'-nucleotidase, adenylate cyclase, and acid phosphatase were 20, 0.39, 0.18, and 0.078, respectively. Adenylate cyclases from hepatocytes and Kupffer cells were stimulated by fluoride ion, GTP, and catecholamines. Hepatocyte adenylate cyclase was also stimulated by glucagon, secretin, vasoactive intestinal polypeptide, and by prostaglandin E1, whereas, the Kupffer cell enzyme was completely insensitive to these hormones. The stimulation of hepatocyte adenylate cyclase by combinations of glucagon plus secretin, or glucagon plus vasoactive intestinal polypeptide, were equivalent to the sum of the individual stimulations. This suggests that the hepatocyte has specific receptors for glucagon and for vasoactive intestinal polypeptide and secretin. Prostaglandin E1 stimulation of hepatocyte adenylate cyclase was not additive to the stimulation caused by polypeptide hormones or catecholamines, nor did prostaglandin E1 decrease stimulation caused by these hormones. Although prostaglandin-sensitive adenylate cyclase was recovered with hepatocytes, 40 to 50% of the total liver prostaglandin-sensitive activity was recovered in a fraction of cell debris mixed with small cells which did not phagocytize colloidal iron."} {"id": "PMID:171270", "title": "Relative thrombogenicity of polydimethylsiloxane and silicone rubber constituents.", "content": "Medical grade silicone rubber (MGSR) is composed of polydimethylsiloxane (PDMS) as well as silica filler, oxidation products from the curing process, and other components. In a test that excludes air-blood interfaces, PDMS radiation cured under nitrogen has a whole blood clotting time 22% longer than MGSR. Curing the PDMS under oxidizing conditions maintains a 10% prolongation, but addition of silica filler to the PDMS returns the clotting time to that of MGSR. Extracting MGSR with solvents other than water appreciably lowers the clotting time. These results indicate the \"pure\" PDMS has an intrinsically high thromboresistance. Thrombogenicity is increased by the use of silica filler and oxidizing cure, as in MGSR.", "contents": "Relative thrombogenicity of polydimethylsiloxane and silicone rubber constituents. Medical grade silicone rubber (MGSR) is composed of polydimethylsiloxane (PDMS) as well as silica filler, oxidation products from the curing process, and other components. In a test that excludes air-blood interfaces, PDMS radiation cured under nitrogen has a whole blood clotting time 22% longer than MGSR. Curing the PDMS under oxidizing conditions maintains a 10% prolongation, but addition of silica filler to the PDMS returns the clotting time to that of MGSR. Extracting MGSR with solvents other than water appreciably lowers the clotting time. These results indicate the \"pure\" PDMS has an intrinsically high thromboresistance. Thrombogenicity is increased by the use of silica filler and oxidizing cure, as in MGSR."} {"id": "PMID:171271", "title": "Correlation of in vivo collagen degradation rate with in vitro measurements.", "content": "The rate of in vitro enzymatic degradation of various materials based on collagen has been determined by a novel mechanochemical method, and has been compared with the extent of degradation resulting from subcutaneous implantation in guinea pigs. In vitro data correlate well with in vivo data. It is suggested that the simple in vitro method described is an effective means of screening a large number of materials based on collagen for their ability to resist degradation during implantation in animals.", "contents": "Correlation of in vivo collagen degradation rate with in vitro measurements. The rate of in vitro enzymatic degradation of various materials based on collagen has been determined by a novel mechanochemical method, and has been compared with the extent of degradation resulting from subcutaneous implantation in guinea pigs. In vitro data correlate well with in vivo data. It is suggested that the simple in vitro method described is an effective means of screening a large number of materials based on collagen for their ability to resist degradation during implantation in animals."} {"id": "PMID:171273", "title": "Improved high-performance liquid chromatographic method for polypeptide antibiotics and its application to study the effects of treatments to reduce microbial levels in bacitracin powder.", "content": "Improvements were made in the high-performance liquid chromatographic (HPLC) method to obtain baseline separation of chromatographic peaks of structurally similar polypeptide components in bacitracin. The improved method uses a 30-cm-long stainless-stell column packed with muBondapak C18. The theoretical plates of the column are approximately 140,000 per meter for the bacitracin A peak. The resolution function between bacitracins B1 and B2 and that between bacitracins A and B2 have been improved 418 and 225%, respectively. The components of bacitracin, bacitracins A, B, C, D, E, F, and G, were fractionated by the countercurrent distribution technique. These components, together with Compound X, a compound separated on a carboxymethylcellulose column, and bacitracin F, obtained by degrading bacitracin A sample at neutral pH, were used to identify peaks in the HPLC chromatogram. Effects of processing methods used to reduce microbial contamination levels in bacitracin powders were evaluated. Heat treatment caused a significant loss of antimicrobial activity (35% reduction), bacitracins A, B1, and B2 were reduced by 37, 22, and 21%, respectively. A significant increase (2.8 times) of bacitracin F, an oxidative degradation compound, was show. Irradiation by 60Co at 1.8 Mrad caused no loss of potency nor change in any of the bacitracin components. Ethylene oxide treatment, on the other hand, caused considerable (46%) reduction of potency. Substantial reduction of areas under the peak of bacitracins A, B1, and B2 (50, 24 and 37%, respectively) were noted. The chromatograms showed numerous unresolved peaks around bacitracins A, B1 and B2,; however, no significant increase in the bacitracin F peak, nor appearance of non-UV absorbing peaks were observed. Peptide antibiotics of the polymyxin group, circulin, colistin, and polymyxin, were also analyzed using the muBondapak C18 column with a linear-gradient elution. A UV monitor was used for polymyxin. A moving-wire flame ionization detector was used to monitor circulin and colistin. A sample of polymyxin, circulin, and colistin may be analyzed in less than 20 min of chromatographic time.", "contents": "Improved high-performance liquid chromatographic method for polypeptide antibiotics and its application to study the effects of treatments to reduce microbial levels in bacitracin powder. Improvements were made in the high-performance liquid chromatographic (HPLC) method to obtain baseline separation of chromatographic peaks of structurally similar polypeptide components in bacitracin. The improved method uses a 30-cm-long stainless-stell column packed with muBondapak C18. The theoretical plates of the column are approximately 140,000 per meter for the bacitracin A peak. The resolution function between bacitracins B1 and B2 and that between bacitracins A and B2 have been improved 418 and 225%, respectively. The components of bacitracin, bacitracins A, B, C, D, E, F, and G, were fractionated by the countercurrent distribution technique. These components, together with Compound X, a compound separated on a carboxymethylcellulose column, and bacitracin F, obtained by degrading bacitracin A sample at neutral pH, were used to identify peaks in the HPLC chromatogram. Effects of processing methods used to reduce microbial contamination levels in bacitracin powders were evaluated. Heat treatment caused a significant loss of antimicrobial activity (35% reduction), bacitracins A, B1, and B2 were reduced by 37, 22, and 21%, respectively. A significant increase (2.8 times) of bacitracin F, an oxidative degradation compound, was show. Irradiation by 60Co at 1.8 Mrad caused no loss of potency nor change in any of the bacitracin components. Ethylene oxide treatment, on the other hand, caused considerable (46%) reduction of potency. Substantial reduction of areas under the peak of bacitracins A, B1, and B2 (50, 24 and 37%, respectively) were noted. The chromatograms showed numerous unresolved peaks around bacitracins A, B1 and B2,; however, no significant increase in the bacitracin F peak, nor appearance of non-UV absorbing peaks were observed. Peptide antibiotics of the polymyxin group, circulin, colistin, and polymyxin, were also analyzed using the muBondapak C18 column with a linear-gradient elution. A UV monitor was used for polymyxin. A moving-wire flame ionization detector was used to monitor circulin and colistin. A sample of polymyxin, circulin, and colistin may be analyzed in less than 20 min of chromatographic time."} {"id": "PMID:171276", "title": "Primary aldosteronism due to a malignant ovarian tumor.", "content": "A case of a young woman with the syndrome of primary aldosteronism and malignant ovarian tumor is reported. Hormone studies revealed extremely high urinary aldosterone, undetectable plasma renin activity, elevated plasma 17beta estradiol and testosterone, and low plasma FSH and LH. Plasma cortisol and urinary 17-hydroxycorticoids were at the upper normal limits. Autopsy disclosed an ovarian tumor, histologically an arrhenoblastoma, with polymorphic aspects. The adrenal glands grossly were normal. Aldosterone was found by the double radioisotopic technique in the neoplastic tissue.", "contents": "Primary aldosteronism due to a malignant ovarian tumor. A case of a young woman with the syndrome of primary aldosteronism and malignant ovarian tumor is reported. Hormone studies revealed extremely high urinary aldosterone, undetectable plasma renin activity, elevated plasma 17beta estradiol and testosterone, and low plasma FSH and LH. Plasma cortisol and urinary 17-hydroxycorticoids were at the upper normal limits. Autopsy disclosed an ovarian tumor, histologically an arrhenoblastoma, with polymorphic aspects. The adrenal glands grossly were normal. Aldosterone was found by the double radioisotopic technique in the neoplastic tissue."} {"id": "PMID:171277", "title": "A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.", "content": "A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.", "contents": "A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease. A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium."} {"id": "PMID:171278", "title": "Endocrine effects of pimozide, a specific dopaminergic blocker.", "content": "Pimozide, a specific blocker of dopaminergic receptors, was administered orally to 10 adult male volumteers for 4 days. Half of the subjects received 4 mg/day and the other half 2 mg/day. Blood samples were obtained the day before, the 4th day of Pimozide, and 4 days after the last dose of the drug for the determination of LH, FSH, GH, PRL, TSH, cortisol and testosterone levels. Twenty-four h urinary collections were obtained for the determination of LH and FSH levels. Plasma LH levels decreased and plasma PRL levels increased in the combined groups during Pimozide. Plasma TSH levels decreased during treatment in the 4 mg group only. Urinary LH and plasma testosterone levels decreased in the post-treatment period in the combined groups. These data support the concept of a dopaminergic control of the secretion of several hormones in the human.", "contents": "Endocrine effects of pimozide, a specific dopaminergic blocker. Pimozide, a specific blocker of dopaminergic receptors, was administered orally to 10 adult male volumteers for 4 days. Half of the subjects received 4 mg/day and the other half 2 mg/day. Blood samples were obtained the day before, the 4th day of Pimozide, and 4 days after the last dose of the drug for the determination of LH, FSH, GH, PRL, TSH, cortisol and testosterone levels. Twenty-four h urinary collections were obtained for the determination of LH and FSH levels. Plasma LH levels decreased and plasma PRL levels increased in the combined groups during Pimozide. Plasma TSH levels decreased during treatment in the 4 mg group only. Urinary LH and plasma testosterone levels decreased in the post-treatment period in the combined groups. These data support the concept of a dopaminergic control of the secretion of several hormones in the human."} {"id": "PMID:171279", "title": "Demonstration of immunoglobulin G receptors induced by human cytomegalovirus.", "content": "Human cytomegalovirus induced a new immunoglobulin G receptor in human fibroblasts. The immunoglobulin G receptor was well localized in the perinuclear region at 48 h postinfection, and antiviral agents blocked its synthesis. The immunoglobulin G receptor bound immunoglobulin G of man and several other species. It may be a source of error in the performance of indirect fluorescence tests for human cytomegalovirus antibody.", "contents": "Demonstration of immunoglobulin G receptors induced by human cytomegalovirus. Human cytomegalovirus induced a new immunoglobulin G receptor in human fibroblasts. The immunoglobulin G receptor was well localized in the perinuclear region at 48 h postinfection, and antiviral agents blocked its synthesis. The immunoglobulin G receptor bound immunoglobulin G of man and several other species. It may be a source of error in the performance of indirect fluorescence tests for human cytomegalovirus antibody."} {"id": "PMID:171280", "title": "Mutant feedback-resistant phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. Phosphoribosylpyrophosphate and purine metabolism in cultured fibroblasts.", "content": "We have reported previously two siblings with gout and uric acid lithiasis associated with excessive purine production. In the erythrocytes of these patients, phosphoribosylpyrophosphate (PRPP) synthetase exhibited resistance to feedback-inhibition by normal cell constituents such as guanosine-5'-diphosphate (GDP) and adenosine-5'-diphosphate (ADP), resulting in superactivity of the mutant enzyme and consequently in increased PRPP content and availability for nucleotide synthesis. Erythrocyte PRPP content and availability were normal in the propositus' parents, his healthy brother and three sons, and they all had normal serum level and urinary excretion of uric acid, except for the mother who was hyperuricosuric. To further characterize this mutation we studied PRPP and purine metabolism in cultured fibroblasts of the affected family. PRPP synthetase in dialyzed lysates of fibroblasts from the propositus and his mother exhibited increased specific activity, more markedly at low inorganic phosphate concentration, and decreased sensitivity to inhibition by ADP and GDP, PRPP content and availability and the rate of de novo purine nucleotide synthesis were markedly increased in the fibroblasts of the propositus and to a lesser extent in the fibroblasts of his mother but were normal in the fibroblasts of the other family members investigated. The fibroblast studies demonstrate the following sequence of abnormalities: feedback-resistance of PRPP synthetase; superactivity of this enzyme in normal physiological milieu; increased availability of PRPP; and increased de novo synthesis of purine nucleotides. The pattern of inheritance of this disorder is compatible with both an X-linked recessive and autosomal dominant traits.", "contents": "Mutant feedback-resistant phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. Phosphoribosylpyrophosphate and purine metabolism in cultured fibroblasts. We have reported previously two siblings with gout and uric acid lithiasis associated with excessive purine production. In the erythrocytes of these patients, phosphoribosylpyrophosphate (PRPP) synthetase exhibited resistance to feedback-inhibition by normal cell constituents such as guanosine-5'-diphosphate (GDP) and adenosine-5'-diphosphate (ADP), resulting in superactivity of the mutant enzyme and consequently in increased PRPP content and availability for nucleotide synthesis. Erythrocyte PRPP content and availability were normal in the propositus' parents, his healthy brother and three sons, and they all had normal serum level and urinary excretion of uric acid, except for the mother who was hyperuricosuric. To further characterize this mutation we studied PRPP and purine metabolism in cultured fibroblasts of the affected family. PRPP synthetase in dialyzed lysates of fibroblasts from the propositus and his mother exhibited increased specific activity, more markedly at low inorganic phosphate concentration, and decreased sensitivity to inhibition by ADP and GDP, PRPP content and availability and the rate of de novo purine nucleotide synthesis were markedly increased in the fibroblasts of the propositus and to a lesser extent in the fibroblasts of his mother but were normal in the fibroblasts of the other family members investigated. The fibroblast studies demonstrate the following sequence of abnormalities: feedback-resistance of PRPP synthetase; superactivity of this enzyme in normal physiological milieu; increased availability of PRPP; and increased de novo synthesis of purine nucleotides. The pattern of inheritance of this disorder is compatible with both an X-linked recessive and autosomal dominant traits."} {"id": "PMID:171281", "title": "Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis.", "content": "Human peripheral blood polymorphonuclear leukocytes, when exposed to appropriate stimuli, generate significant amounts of superoxide anion (O-.2), a highly reactive molecule which is possibly involved in bacterial killing. Since the subcellular localization and mechanism of activation of O-.2 generating systems are unknown, we have investigated superoxide dismutase-inhibitable cytochrome c reduction (attributable to O-.2) by, and lysosomal enzyme release from, normal polymorphonuclear leukocytes and cells rendered incapable of ingesting particles by treatment with cytochalasin B. Neither phagocytosis nor lysosomal degranulation were prerequisites for enhanced O-.2 generation. Cytochalasin B-treated cells exposed to (a) serum-treated zymosan, a C3b receptor stimulus; (b) heat aggregated human IgG, an Fc receptor stimulus; and (c) the complement component, C5a, generated enhanced amounts of O-.2 in a time and concentration-dependent fashion. These cells also responded by releasing lysosomal enzymes, but there was no correlation between the ability of any immune reactant to provoke enzyme release and its ability to stimulate O-.2 generation. The three stimuli also enhanced O-.2 generation by normal (untreated) polymorphonuclear leukocytes, but only serum-treated zymosan and aggregated IgG were capable of provoking lysosomal enzyme release from normal cells. Untreated zymosan and native IgG neither stimulated O-.2 production nor provoked lysomal enzyme release. Since enhanced O-.2 production was stimulated by immune reactants in the absence of phagocytosis, the O-.2 generating system is very likely associated with the external plasma membrane of the polymorphonuclear leukocyte. Leukocyte membrane receptors for complement and immunoglobulins may therefore not only serve in particle recognition but also may initiate biochemical events which accompany phagocytosis and killing.", "contents": "Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. Human peripheral blood polymorphonuclear leukocytes, when exposed to appropriate stimuli, generate significant amounts of superoxide anion (O-.2), a highly reactive molecule which is possibly involved in bacterial killing. Since the subcellular localization and mechanism of activation of O-.2 generating systems are unknown, we have investigated superoxide dismutase-inhibitable cytochrome c reduction (attributable to O-.2) by, and lysosomal enzyme release from, normal polymorphonuclear leukocytes and cells rendered incapable of ingesting particles by treatment with cytochalasin B. Neither phagocytosis nor lysosomal degranulation were prerequisites for enhanced O-.2 generation. Cytochalasin B-treated cells exposed to (a) serum-treated zymosan, a C3b receptor stimulus; (b) heat aggregated human IgG, an Fc receptor stimulus; and (c) the complement component, C5a, generated enhanced amounts of O-.2 in a time and concentration-dependent fashion. These cells also responded by releasing lysosomal enzymes, but there was no correlation between the ability of any immune reactant to provoke enzyme release and its ability to stimulate O-.2 generation. The three stimuli also enhanced O-.2 generation by normal (untreated) polymorphonuclear leukocytes, but only serum-treated zymosan and aggregated IgG were capable of provoking lysosomal enzyme release from normal cells. Untreated zymosan and native IgG neither stimulated O-.2 production nor provoked lysomal enzyme release. Since enhanced O-.2 production was stimulated by immune reactants in the absence of phagocytosis, the O-.2 generating system is very likely associated with the external plasma membrane of the polymorphonuclear leukocyte. Leukocyte membrane receptors for complement and immunoglobulins may therefore not only serve in particle recognition but also may initiate biochemical events which accompany phagocytosis and killing."} {"id": "PMID:171282", "title": "Collagenase in scleroderma.", "content": "Collagenase activity was measured by direct assay in skins from 12 patients afflicted with systemic sclerosis. In seven of those cases where extensive involvement of the forearm and trunk skin existed, collagenase activity of the involved skin was minimal or absent. Moreover, in the same patient, regions of marked skin involvement (e.g., forearm) showed no collagenase activity, when clinically uninvolved areas (thigh) exhibited normal or nearly normal levels of enzyme activity. In other patients where clinical symptoms were systemic and not associated significantly with the skin, collagenase activity approximated normal levels. Measurements of collagenase activity and tensile strength in another condition (basal cell carcinoma) that includes changes in mechanical properties of skin that any be regarded as the opposite end of the spectrum from those of sclerodermatous skin support a general correlation between collagenase activity and tensile strength. These studies indicate that the major defect responsible for the hidebound skin lesions of scleroderma may be decreased collagenase activity.", "contents": "Collagenase in scleroderma. Collagenase activity was measured by direct assay in skins from 12 patients afflicted with systemic sclerosis. In seven of those cases where extensive involvement of the forearm and trunk skin existed, collagenase activity of the involved skin was minimal or absent. Moreover, in the same patient, regions of marked skin involvement (e.g., forearm) showed no collagenase activity, when clinically uninvolved areas (thigh) exhibited normal or nearly normal levels of enzyme activity. In other patients where clinical symptoms were systemic and not associated significantly with the skin, collagenase activity approximated normal levels. Measurements of collagenase activity and tensile strength in another condition (basal cell carcinoma) that includes changes in mechanical properties of skin that any be regarded as the opposite end of the spectrum from those of sclerodermatous skin support a general correlation between collagenase activity and tensile strength. These studies indicate that the major defect responsible for the hidebound skin lesions of scleroderma may be decreased collagenase activity."} {"id": "PMID:171283", "title": "Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.", "content": "High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance.", "contents": "Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma. High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance."} {"id": "PMID:171284", "title": "Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor.", "content": "We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor.", "contents": "Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor. We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor."} {"id": "PMID:171285", "title": "Adenoid cystic carcinoma of the breast: prevalence, diagnostic criteria, and histogenesis.", "content": "Three cases of adenoid cystic carcinoma have been identified in a 10-year review of 2686 cases of breast carcinoma. The criteria necessary for diagnosis have been reviewed with particular reference to cribriform intraduct carcinoma and adenocarcinoma of the breast with small, dark, 'basaloid'-cell pattern. The most important single diagnostic criterion of adenoid cystic carcinoma is a biphasic cellular pattern which may be aded by the demonstration of two types of mucin stromal acid mucopolysaccharide and ductal neutral mucopolysaccharide. This tumour most frequently presents as a painful or tender mass near the areola, and it carries a uniquely favourable prognosis when compared with similar tumours elsewhere in the body. Actomyosin has been demonstrated in all three tumours by an immunofluorescent method, and this supports a predominantly myoepithelial origin.", "contents": "Adenoid cystic carcinoma of the breast: prevalence, diagnostic criteria, and histogenesis. Three cases of adenoid cystic carcinoma have been identified in a 10-year review of 2686 cases of breast carcinoma. The criteria necessary for diagnosis have been reviewed with particular reference to cribriform intraduct carcinoma and adenocarcinoma of the breast with small, dark, 'basaloid'-cell pattern. The most important single diagnostic criterion of adenoid cystic carcinoma is a biphasic cellular pattern which may be aded by the demonstration of two types of mucin stromal acid mucopolysaccharide and ductal neutral mucopolysaccharide. This tumour most frequently presents as a painful or tender mass near the areola, and it carries a uniquely favourable prognosis when compared with similar tumours elsewhere in the body. Actomyosin has been demonstrated in all three tumours by an immunofluorescent method, and this supports a predominantly myoepithelial origin."} {"id": "PMID:171286", "title": "A histochemical method of differentiating lower gastrointestinal tract mucin from other mucins in primary or metastatic tumours.", "content": "Epithelial mucins of the normal terminal ileum, caecum, colon, and rectum of man are unique in that they alone exhibit staining following the periodate-borohydride/KOH/PAS technique. Application of this technique enables one to differentiate those mucin-producting metastases arising from adenocarcinoma of the lower gastrointestinal tract from those arising elsewhere, and may occasionally be useful in determining the site of the primary tumour when it is in doubt. Furthermore, it was found to be especially useful in distinguishing between primary adenocarcinoma of the lung and metastases in the lung from adenocarcinoma of the lower gastrointestinal tract.", "contents": "A histochemical method of differentiating lower gastrointestinal tract mucin from other mucins in primary or metastatic tumours. Epithelial mucins of the normal terminal ileum, caecum, colon, and rectum of man are unique in that they alone exhibit staining following the periodate-borohydride/KOH/PAS technique. Application of this technique enables one to differentiate those mucin-producting metastases arising from adenocarcinoma of the lower gastrointestinal tract from those arising elsewhere, and may occasionally be useful in determining the site of the primary tumour when it is in doubt. Furthermore, it was found to be especially useful in distinguishing between primary adenocarcinoma of the lung and metastases in the lung from adenocarcinoma of the lower gastrointestinal tract."} {"id": "PMID:171290", "title": "Membranes of mammary gland. XI. Marker enzyme distribution profiles for membranous components from bovine mammary gland.", "content": "Enzyme distribution profiles of clarified bovine mammary homogenates separated by equilibrium centrifugation on linear sucrose gradients suggested that several of the commonly utilized marker enzymes for rat liver are also valid markers for mammary cellular components. These marker enzymes include: Succinate dehydrogenase (mitochondria), nicotinamide adenine dinucleotide phosphate cytochrome c reductase and, to a lesser extent, retenone insensitive nicotinamide adenine dinucleotide cytochrome c reductase (endoplasmic reticulum), galactosyl transferase (Golgi apparatus), 5'-nucleotidase (plasma membranes), uric acid oxidase (microbodies), and acid phosphatase (lysosomes). Rotenone sensitive nicotinamide adenine dinucleotide cytochrome c reductase and sodium, potassium, magnesium-stimulated adenosine triphosphatase were widely distributed among subcellular fractions and are not valid marker enzymes. The boyant densities determined for the above fractions should aid in design of methods to obtain enriched sources of these components for analysis.", "contents": "Membranes of mammary gland. XI. Marker enzyme distribution profiles for membranous components from bovine mammary gland. Enzyme distribution profiles of clarified bovine mammary homogenates separated by equilibrium centrifugation on linear sucrose gradients suggested that several of the commonly utilized marker enzymes for rat liver are also valid markers for mammary cellular components. These marker enzymes include: Succinate dehydrogenase (mitochondria), nicotinamide adenine dinucleotide phosphate cytochrome c reductase and, to a lesser extent, retenone insensitive nicotinamide adenine dinucleotide cytochrome c reductase (endoplasmic reticulum), galactosyl transferase (Golgi apparatus), 5'-nucleotidase (plasma membranes), uric acid oxidase (microbodies), and acid phosphatase (lysosomes). Rotenone sensitive nicotinamide adenine dinucleotide cytochrome c reductase and sodium, potassium, magnesium-stimulated adenosine triphosphatase were widely distributed among subcellular fractions and are not valid marker enzymes. The boyant densities determined for the above fractions should aid in design of methods to obtain enriched sources of these components for analysis."} {"id": "PMID:171291", "title": "Variability in structural carbohydrates and in vitro digestibility of forages. 3. Guar (Cyamopsis tetragonoloba).", "content": "Thirteen genotypes of guar (Cyamopsis tetragonoloba) were compared with the local variety for structural carbohydrates and in vitro digestibility. Neutral detergent fiber, acid detergent fiber, lignin, and acid insoluble ash varied 31.2 to 44.4, 26.1 to 37.4, 6.8 to 11.1, and .30 to 1.11%. Cellulose varied from 16.6 to 28.1% whereas hemicellulose content ranged between 3.6 and 9.2%. In vitro digestibility of dry matter ranged between 62.8 to 71.2% Variation in protein, mineral matter, and percentage of dry matter was from 12.7 to 19.7, 9.4 to 12.3, and 23.0 to 26.7. Neutral detergent fiber and lignin plus silica were correlated negatively with in vitro digestibility of dry matter. A genetic manipulation of breeding material can bring about a highly nutritive genotype of guar.", "contents": "Variability in structural carbohydrates and in vitro digestibility of forages. 3. Guar (Cyamopsis tetragonoloba). Thirteen genotypes of guar (Cyamopsis tetragonoloba) were compared with the local variety for structural carbohydrates and in vitro digestibility. Neutral detergent fiber, acid detergent fiber, lignin, and acid insoluble ash varied 31.2 to 44.4, 26.1 to 37.4, 6.8 to 11.1, and .30 to 1.11%. Cellulose varied from 16.6 to 28.1% whereas hemicellulose content ranged between 3.6 and 9.2%. In vitro digestibility of dry matter ranged between 62.8 to 71.2% Variation in protein, mineral matter, and percentage of dry matter was from 12.7 to 19.7, 9.4 to 12.3, and 23.0 to 26.7. Neutral detergent fiber and lignin plus silica were correlated negatively with in vitro digestibility of dry matter. A genetic manipulation of breeding material can bring about a highly nutritive genotype of guar."} {"id": "PMID:171293", "title": "Odontodysplasia.", "content": "Results of a comprehensive dental examination, including a histologic evaluation, of a patient showing unilateral odontodysplasia revealed no hint as to the origin of the abnormality. A complete medical examination also resulted in negative findings, with the excetion of congenital bilateral talipes equinovarus. The genetic history was negative, and results of chromosomal studies of the child and her mother revealed no abnormalities. Neither had an anatomic or a functional abnormality, with the exception of the odontodysplasia in the child. Results of laboratory studies including complete blood counts, urinalyses, ferric chloride tests of the urine, and electrolyte tests also were negative. The special considerations given in this case in an attempt to establish a possible causation of the abnormality were inconclusive. We think, however, that the management of the patient was successful in regard to the prosthetic appliance, and every attempt will be made to follow up the patient to ensure a good prognosis of the remaining developing dentition.", "contents": "Odontodysplasia. Results of a comprehensive dental examination, including a histologic evaluation, of a patient showing unilateral odontodysplasia revealed no hint as to the origin of the abnormality. A complete medical examination also resulted in negative findings, with the excetion of congenital bilateral talipes equinovarus. The genetic history was negative, and results of chromosomal studies of the child and her mother revealed no abnormalities. Neither had an anatomic or a functional abnormality, with the exception of the odontodysplasia in the child. Results of laboratory studies including complete blood counts, urinalyses, ferric chloride tests of the urine, and electrolyte tests also were negative. The special considerations given in this case in an attempt to establish a possible causation of the abnormality were inconclusive. We think, however, that the management of the patient was successful in regard to the prosthetic appliance, and every attempt will be made to follow up the patient to ensure a good prognosis of the remaining developing dentition."} {"id": "PMID:171292", "title": "Effect of toothbrush variables on wear of dentin produced by four abrasives.", "content": "A study was conducted to explore the effect of brush brand, brush hardness, and the concentration of abrasive on the wear of human dentin by four dentifrice abrasives. The two hard brushes produced similar and high levels of abrasion, whereas the two medium brushes of the same brands gave dissimilar and lower levels of abrasion. Dilution changed the ranking of two of the four abrasives.", "contents": "Effect of toothbrush variables on wear of dentin produced by four abrasives. A study was conducted to explore the effect of brush brand, brush hardness, and the concentration of abrasive on the wear of human dentin by four dentifrice abrasives. The two hard brushes produced similar and high levels of abrasion, whereas the two medium brushes of the same brands gave dissimilar and lower levels of abrasion. Dilution changed the ranking of two of the four abrasives."} {"id": "PMID:171306", "title": "Toxic and reactogenic properties of pertussis bacteria (experimental and clinical studies).", "content": "The results of the study revealed correlation between the reactogenicity of pertussis vaccines in epidemiological observations and the toxic properties of pertussis bacteria in experiment. Quantitative and qualitative differences were found between the toxic factors in pertussis bacteria depending on their type-specific serological activity. Serotype 1.0.3 microbes exhibit more pronounced toxicity which accounts for the greater reactogenicity of vaccines prepared from this serotype as compared with the preparation produced from the serotype 1.2.3. The obtained results suggest the necessity of considering the greater toxicity of the serotype 1.0.3 in the preparation of pertussis vaccines.", "contents": "Toxic and reactogenic properties of pertussis bacteria (experimental and clinical studies). The results of the study revealed correlation between the reactogenicity of pertussis vaccines in epidemiological observations and the toxic properties of pertussis bacteria in experiment. Quantitative and qualitative differences were found between the toxic factors in pertussis bacteria depending on their type-specific serological activity. Serotype 1.0.3 microbes exhibit more pronounced toxicity which accounts for the greater reactogenicity of vaccines prepared from this serotype as compared with the preparation produced from the serotype 1.2.3. The obtained results suggest the necessity of considering the greater toxicity of the serotype 1.0.3 in the preparation of pertussis vaccines."} {"id": "PMID:171307", "title": "Occurrence of antibodies to type 2 herpes simplex virus in the sera of town population.", "content": "In order to obtain a more detailed knowledge of the ecology of genital herpesvirus in Czechoslovak geographic and socioeconomic conditions, a total of 1 246 sera of town population, collected by the method of random selection from persons of different age groups in the town of Ostrava were examined in microneutralization reaction for antibodies to type 2 and type 1 herpes simplex virus. Antibodies to HSV-1 were present even in the youngest age groups 0--4 and 5--9 and positive findings in the older age groups ranged from 52 to 82% while antibodies to type 2 herpesvirus were found for the first time at the age of 14 (in one case); in adult persons they occurred in 17--26%. The mentioned results correspond to the sexual manner of transmission of genital herpesvirus and are in keeping with published findings.", "contents": "Occurrence of antibodies to type 2 herpes simplex virus in the sera of town population. In order to obtain a more detailed knowledge of the ecology of genital herpesvirus in Czechoslovak geographic and socioeconomic conditions, a total of 1 246 sera of town population, collected by the method of random selection from persons of different age groups in the town of Ostrava were examined in microneutralization reaction for antibodies to type 2 and type 1 herpes simplex virus. Antibodies to HSV-1 were present even in the youngest age groups 0--4 and 5--9 and positive findings in the older age groups ranged from 52 to 82% while antibodies to type 2 herpesvirus were found for the first time at the age of 14 (in one case); in adult persons they occurred in 17--26%. The mentioned results correspond to the sexual manner of transmission of genital herpesvirus and are in keeping with published findings."} {"id": "PMID:171308", "title": "Human leukemia-associated antigens: detection on cells of established lymphoblastoid lines.", "content": "Primate and rabbit antisera to different morphologic classes of human leukemia cells, after appropriate absorptions, detected leukemia-associated antigens present on cultured lymphoblastoid cell lines derived from leukemia patients. The primate antisera distinguished antigens on cells derived from myeloid leukemia patients from those on cells derived from lymphocytic leukemia patients. Of particular interest was the fact that antigens of myeloid leukemia, but not of lymphatic leukemia, were detected on lymphoid cell lines established from blood of patients with myeloid leukemia. One of four lymphoblastoid cell lines derived from normal donors expressed antigens of lymphatic leukemia. Leukemia-associated antigens were not found on the HRIK lymphoblastoid line derived from a Burkitt's lymphoma patient on skin fibroblasts or HeLa cells. Expression of these antigens on cultured cells derived from leukemia patients could not be related to the presence of the EB virus or the EB virus genome. Rabbit antisera detected antigens common to cells from patients with myeloid and lymphocytic leukemia. Absorption experiments demonstrated that the antigens detected on cell lines derived from leukemia patients are similar to those detected by the primate and rabbit antisera on fresh peripheral blood leukemic cells. The serologic detection of leukemia-associated antigens on lymphoblastoid cell lines indicates that some of these cultures contain cells with antigenic properties similar to those of human peripheral blood leukemic cells.", "contents": "Human leukemia-associated antigens: detection on cells of established lymphoblastoid lines. Primate and rabbit antisera to different morphologic classes of human leukemia cells, after appropriate absorptions, detected leukemia-associated antigens present on cultured lymphoblastoid cell lines derived from leukemia patients. The primate antisera distinguished antigens on cells derived from myeloid leukemia patients from those on cells derived from lymphocytic leukemia patients. Of particular interest was the fact that antigens of myeloid leukemia, but not of lymphatic leukemia, were detected on lymphoid cell lines established from blood of patients with myeloid leukemia. One of four lymphoblastoid cell lines derived from normal donors expressed antigens of lymphatic leukemia. Leukemia-associated antigens were not found on the HRIK lymphoblastoid line derived from a Burkitt's lymphoma patient on skin fibroblasts or HeLa cells. Expression of these antigens on cultured cells derived from leukemia patients could not be related to the presence of the EB virus or the EB virus genome. Rabbit antisera detected antigens common to cells from patients with myeloid and lymphocytic leukemia. Absorption experiments demonstrated that the antigens detected on cell lines derived from leukemia patients are similar to those detected by the primate and rabbit antisera on fresh peripheral blood leukemic cells. The serologic detection of leukemia-associated antigens on lymphoblastoid cell lines indicates that some of these cultures contain cells with antigenic properties similar to those of human peripheral blood leukemic cells."} {"id": "PMID:171309", "title": "Immune and antibody responses to an isolated capsid protein of foot-and-mouth disease virus.", "content": "The purified capsid proteins VP1, VP2, and VP3 of foot-and-mouth disease virus type A12 strain 119 emulsified with incomplete Freund's adjuvant were studied in swine and guinea pigs. Swine inoculated on days 0, 28, and 60 with 100-mug doses of VP3 were protected by day 82 against exposure to infected swine. Serums from animals inoculated with VP3 contained viral precipitating and neutralizing antibodies, but such serums recognized fewer viral antigenic determinants than did antiviral serums. Capsid proteins VP1 and VP2 did not produce detectable antiviral antibody in guinea pigs, and antiviral antibody responses in swine to a mixture of VP1, VP2, and VP3 were lower than the responses to VP3 alone. However, when swine were inoculated with VP1, VP2, and VP3 separately at different body sites, no interference with the response to VP3 was observed. Vaccine containing VP3 isolated from acetylethylenimine-treated virus appeared less protective for swine than vaccine containing VP3 from nontreated virus. Trypsinized virus, which contains the cleaved peptides VP3a and VP3b rather than intact VP3, produced approximately the same levels of antiviral antibody responses in guinea pigs as did virus. Conversely, an isolated mixture of VP3a and VP3b did not produce detectable antiviral antibody responses in guinea pigs. The VP3a-VP3b mixture did, however, sensitize guinea pigs to elicit such responses following reinoculation with a marginally effective dose of trypsinized virus.", "contents": "Immune and antibody responses to an isolated capsid protein of foot-and-mouth disease virus. The purified capsid proteins VP1, VP2, and VP3 of foot-and-mouth disease virus type A12 strain 119 emulsified with incomplete Freund's adjuvant were studied in swine and guinea pigs. Swine inoculated on days 0, 28, and 60 with 100-mug doses of VP3 were protected by day 82 against exposure to infected swine. Serums from animals inoculated with VP3 contained viral precipitating and neutralizing antibodies, but such serums recognized fewer viral antigenic determinants than did antiviral serums. Capsid proteins VP1 and VP2 did not produce detectable antiviral antibody in guinea pigs, and antiviral antibody responses in swine to a mixture of VP1, VP2, and VP3 were lower than the responses to VP3 alone. However, when swine were inoculated with VP1, VP2, and VP3 separately at different body sites, no interference with the response to VP3 was observed. Vaccine containing VP3 isolated from acetylethylenimine-treated virus appeared less protective for swine than vaccine containing VP3 from nontreated virus. Trypsinized virus, which contains the cleaved peptides VP3a and VP3b rather than intact VP3, produced approximately the same levels of antiviral antibody responses in guinea pigs as did virus. Conversely, an isolated mixture of VP3a and VP3b did not produce detectable antiviral antibody responses in guinea pigs. The VP3a-VP3b mixture did, however, sensitize guinea pigs to elicit such responses following reinoculation with a marginally effective dose of trypsinized virus."} {"id": "PMID:171310", "title": "Cyclic GMP and lectin-induced lymphocyte activation.", "content": "Purified human peripheral lymphocytes incubated with the mitogenic plant lectins phytohemagglutinin and concanavalin A were examined for alterations in intracellular cGMP and cAMP under a variety of experimental conditions and using multiple techniques for the isolation and purification of cGMP and cAMP before assay of the cyclic nucleotides by radioimmunoassay. In contrast to work reported by others, we have been unable to demonstrate consistent increases in cGMP under any of the experimental conditions used and with any of the various purification schemes. In these same experiments exogenous cGMP added to the lymphocytes could be measured, and the immunoreactive material was destroyed by cyclic nucleotide phosphodiesterase, indicating that our inability to measure increases in cGMP was not caused by our inability to measure cGMP. Under identical experimental conditions, small but consistent and statistically significant increases in cAMP were noted. In addition, other parameters of lymphocyte activation, 45Ca uptake (an early parameter), and incorporation of 3H thymidine into DNA were unimpaired. These data call to question the concept of cGMP as the second messenger in lectin-stimulated human peripheral lymphocytes.", "contents": "Cyclic GMP and lectin-induced lymphocyte activation. Purified human peripheral lymphocytes incubated with the mitogenic plant lectins phytohemagglutinin and concanavalin A were examined for alterations in intracellular cGMP and cAMP under a variety of experimental conditions and using multiple techniques for the isolation and purification of cGMP and cAMP before assay of the cyclic nucleotides by radioimmunoassay. In contrast to work reported by others, we have been unable to demonstrate consistent increases in cGMP under any of the experimental conditions used and with any of the various purification schemes. In these same experiments exogenous cGMP added to the lymphocytes could be measured, and the immunoreactive material was destroyed by cyclic nucleotide phosphodiesterase, indicating that our inability to measure increases in cGMP was not caused by our inability to measure cGMP. Under identical experimental conditions, small but consistent and statistically significant increases in cAMP were noted. In addition, other parameters of lymphocyte activation, 45Ca uptake (an early parameter), and incorporation of 3H thymidine into DNA were unimpaired. These data call to question the concept of cGMP as the second messenger in lectin-stimulated human peripheral lymphocytes."} {"id": "PMID:171313", "title": "Experimental pneumococcal meningitis. II. Characterization and quantitation of the inflammatory process.", "content": "For the systematic study of the role of inflammation in the morbidity and mortality associated with bacterial meningitis, techniques for quantitation of the inflammatory reaction in the meninges of rabbits with experimental pneumococcal infection were developed. The brains of 19 infected animals were removed intact, and the area of inflammation in microscopic sections was quantitated by an electronic X-Y plotter connected to a computer. Exudate was maximal along the ventral surface of the brain at the level of the cerebellum. Inflammation increased progressively with time and peaked at 72 hr. In a separate group of 29 animals, lactic acid dehydrogenase concentrations in cerebrospinal fluid increased significantly during infection, and the rate of increase wirh time coincided with the increase in inflammation documented histologically. The described method of quantitating inflammation in the meninges during experimental meningitis makes it possible to study the increase in granulocyte involvement with time. The establishment of a direct relation between the concentration of lactic acid dehydrogenase in the cerebrospinal fluid and the inflammatory mass validates the use of lactic acid dehydrogenase as an indicator of inflammation.", "contents": "Experimental pneumococcal meningitis. II. Characterization and quantitation of the inflammatory process. For the systematic study of the role of inflammation in the morbidity and mortality associated with bacterial meningitis, techniques for quantitation of the inflammatory reaction in the meninges of rabbits with experimental pneumococcal infection were developed. The brains of 19 infected animals were removed intact, and the area of inflammation in microscopic sections was quantitated by an electronic X-Y plotter connected to a computer. Exudate was maximal along the ventral surface of the brain at the level of the cerebellum. Inflammation increased progressively with time and peaked at 72 hr. In a separate group of 29 animals, lactic acid dehydrogenase concentrations in cerebrospinal fluid increased significantly during infection, and the rate of increase wirh time coincided with the increase in inflammation documented histologically. The described method of quantitating inflammation in the meninges during experimental meningitis makes it possible to study the increase in granulocyte involvement with time. The establishment of a direct relation between the concentration of lactic acid dehydrogenase in the cerebrospinal fluid and the inflammatory mass validates the use of lactic acid dehydrogenase as an indicator of inflammation."} {"id": "PMID:171314", "title": "Sensitivities of neurotropic arboviruses to human interferon.", "content": "The sensitivities of selected neurotropic arboviruses (St. Louis encephalitis, Western equine encephaltis, and La Crosse viruses) to human interferon and polyriboinosinic-polyribocytidylic acid (poly I-poly C) were determined in primary human fetal glial cell cultures. The sensitivities were measured by an end point (inhibition of virus yield). All of the viruses were sensitive to human interferon and poly I-poly C; St. Louis encephalitis and Western equine encephalitis viruses were inhibited at concentrations of interferon actually measured in the brains of persons who died from these infections. For St. Louis encephalitis and Western equine encephalitis viruses, viral replication and induction of interferon varied among cell cultures derived from individual fetuses. The present experiments may provide an approach toward understanding the problem of different host susceptibilities to neurotropic arbovirus infections.", "contents": "Sensitivities of neurotropic arboviruses to human interferon. The sensitivities of selected neurotropic arboviruses (St. Louis encephalitis, Western equine encephaltis, and La Crosse viruses) to human interferon and polyriboinosinic-polyribocytidylic acid (poly I-poly C) were determined in primary human fetal glial cell cultures. The sensitivities were measured by an end point (inhibition of virus yield). All of the viruses were sensitive to human interferon and poly I-poly C; St. Louis encephalitis and Western equine encephalitis viruses were inhibited at concentrations of interferon actually measured in the brains of persons who died from these infections. For St. Louis encephalitis and Western equine encephalitis viruses, viral replication and induction of interferon varied among cell cultures derived from individual fetuses. The present experiments may provide an approach toward understanding the problem of different host susceptibilities to neurotropic arbovirus infections."} {"id": "PMID:171315", "title": "Epidemiology of cytomegalovirus infection after transplantation and immunosuppression.", "content": "Viral infections and clinical complications were studied during hemodialysis and after renal transplantation. Active cytomegalovirus infection developed in 96% of patients after renal transplantation; reactivation of herpes simplex, varicella-zoster, and Epstein-Barr viruses was found in 35%, 24%, and 0% of patients, respectively. Cytomegalovirus viremia developed in 42% of patients an average of two months after renal transplantation, lasted 1.75 (+/- 1.5) months (except in one patient with chronic viremia), and was followed by chronic viruria. Higher titers of infectious cytomegalovirus were found in the polymorphonuclear than in the mononuclear leukocyte fraction. Reactivation of a latent infection and, less likely, respiratory infection appear to be the most probable mechanisms of cytomegalovirus infection after renal transplantation. One to three months after transplant, cytomegalovirus infection may be related to fever, arthralgia, pneumonitis, and leukopenia; three to four months after transplant, the virus may be related to hepatitis; and 12-30 months after transplant, it may be related to retinitis in patients with chronic viremia. Although other causes of these complications are possible, herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, measles virus, adenovirus, hepatitis B virus, and Toxoplasma gondii appear to be of lesser importance than cytomegalovirus in this respect.", "contents": "Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. Viral infections and clinical complications were studied during hemodialysis and after renal transplantation. Active cytomegalovirus infection developed in 96% of patients after renal transplantation; reactivation of herpes simplex, varicella-zoster, and Epstein-Barr viruses was found in 35%, 24%, and 0% of patients, respectively. Cytomegalovirus viremia developed in 42% of patients an average of two months after renal transplantation, lasted 1.75 (+/- 1.5) months (except in one patient with chronic viremia), and was followed by chronic viruria. Higher titers of infectious cytomegalovirus were found in the polymorphonuclear than in the mononuclear leukocyte fraction. Reactivation of a latent infection and, less likely, respiratory infection appear to be the most probable mechanisms of cytomegalovirus infection after renal transplantation. One to three months after transplant, cytomegalovirus infection may be related to fever, arthralgia, pneumonitis, and leukopenia; three to four months after transplant, the virus may be related to hepatitis; and 12-30 months after transplant, it may be related to retinitis in patients with chronic viremia. Although other causes of these complications are possible, herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, measles virus, adenovirus, hepatitis B virus, and Toxoplasma gondii appear to be of lesser importance than cytomegalovirus in this respect."} {"id": "PMID:171316", "title": "Decreased interferon response by lymphocytes from children with chronic hepatitis.", "content": "Since a decreased interferon response has been linked with certain chronic viral infections, a preliminary study was undertaken to determine whether an altered interferon response may be involved in the pathogenesis of chronic hepatitis, a complication of type B hepatitis. The production of interferon by lymphocytes from patients with chronic hepatitis was compared with the production by lymphocytes from normal subjects. The amount of interferon produced by paramyxovirus-stimulated lymphocytes from 16 patients was substantially smaller than that produced by lymphocytes from 12 healthy donors. The results indicate that decreased production of interferon may be responsible for the chronicity of the disease. However, further studies are necessary to establish causality.", "contents": "Decreased interferon response by lymphocytes from children with chronic hepatitis. Since a decreased interferon response has been linked with certain chronic viral infections, a preliminary study was undertaken to determine whether an altered interferon response may be involved in the pathogenesis of chronic hepatitis, a complication of type B hepatitis. The production of interferon by lymphocytes from patients with chronic hepatitis was compared with the production by lymphocytes from normal subjects. The amount of interferon produced by paramyxovirus-stimulated lymphocytes from 16 patients was substantially smaller than that produced by lymphocytes from 12 healthy donors. The results indicate that decreased production of interferon may be responsible for the chronicity of the disease. However, further studies are necessary to establish causality."} {"id": "PMID:171318", "title": "Experimental herpes simplex virus encephalitis: Comparative effects of treatment with cytosine arabinoside and adenine arabinoside.", "content": "Experimental herpesvirus encephalitis in weanling mice was treated with either cytosine arabinoside or adenine arabinoside to determine the comparative effectiveness of the two compounds on survival and on the concentration of virus in the brain. The uniformly fatal course of the encephalitis was not altered by any dosage of cytosine arabinoside. In contrast, treatment with adenine arabinoside resulted in long-term survival of the majority of the infected animals. The concentration of virus measured in the brains of animals treated with two different dosages of cytosine arabinoside indicated initial suppression of viral replication with a subsequent rise to levels higher than those in the untreated controls. In the brains of adenine arabinoside-treated animals, titers of virus gradually diminished to undetectable levels by the eighth day after institution of therapy.", "contents": "Experimental herpes simplex virus encephalitis: Comparative effects of treatment with cytosine arabinoside and adenine arabinoside. Experimental herpesvirus encephalitis in weanling mice was treated with either cytosine arabinoside or adenine arabinoside to determine the comparative effectiveness of the two compounds on survival and on the concentration of virus in the brain. The uniformly fatal course of the encephalitis was not altered by any dosage of cytosine arabinoside. In contrast, treatment with adenine arabinoside resulted in long-term survival of the majority of the infected animals. The concentration of virus measured in the brains of animals treated with two different dosages of cytosine arabinoside indicated initial suppression of viral replication with a subsequent rise to levels higher than those in the untreated controls. In the brains of adenine arabinoside-treated animals, titers of virus gradually diminished to undetectable levels by the eighth day after institution of therapy."} {"id": "PMID:171319", "title": "Direct visualization of enveloped Epstein-Barr Herpesvirus in throat washing with leukocyte-transforming activity.", "content": "Mature enveloped virions belonging to the herpes class were found in a concentrated, partially purified specimen of throat washings from a patient undergoing immunosuppressive therapy for prevention of renal homograft rejection. This throat washing contained a high titer of biologically active Epstein-Barr virus and no other human herpesviruses. Epstein-Barr virions were not detected in throat washings from patients with mononucleosis that had only low titers of transforming activity.", "contents": "Direct visualization of enveloped Epstein-Barr Herpesvirus in throat washing with leukocyte-transforming activity. Mature enveloped virions belonging to the herpes class were found in a concentrated, partially purified specimen of throat washings from a patient undergoing immunosuppressive therapy for prevention of renal homograft rejection. This throat washing contained a high titer of biologically active Epstein-Barr virus and no other human herpesviruses. Epstein-Barr virions were not detected in throat washings from patients with mononucleosis that had only low titers of transforming activity."} {"id": "PMID:171320", "title": "Experimental infection of chimpanzees with hepatitis A virus.", "content": "The susceptibility of chimpanzees to viral hepatitis type A was examined with immine electron microscopy. Of four seronegative infant chimpanzees, two were inoculated with a hepatitis A acute-phase stool filtrate rich in 27 nm virus-like hepatitis A antigen (HA Ag) particles, and two were inoculated with an HA Ag-negative preinfection stool filtrate. One of each pair of chimpanzees was inoculated intravenously, the other orally. One month later both chimpanzees that had received the HA Ag-positive filtrate developed biochemical, histologic, and clinical evidence of acute viral hepatitis. HA Ag particle (27 nm) were detected in their stools by immune electron microscopy; particle shedding followed a pattern similar to that in human volunteers. Immune electron microscopy also showed that antibody HA Ag had developed in the convalescent-phase sera of the infected chimpanzees. Control animals remained free of illness at this time but did develop hepatitis three to five weeks after exposure to the two infected chimpanzee-. The infectious inoculum was titrated in two additional seronegative chimpanzees. It was concluded that hepatitis a can be successfully transmitted to seronegative chimpanzees. Moreover, these studies provide further evidence that the 27-nm virus-like HA Ag particle is the etiologic agent of viral hepatitis type A.", "contents": "Experimental infection of chimpanzees with hepatitis A virus. The susceptibility of chimpanzees to viral hepatitis type A was examined with immine electron microscopy. Of four seronegative infant chimpanzees, two were inoculated with a hepatitis A acute-phase stool filtrate rich in 27 nm virus-like hepatitis A antigen (HA Ag) particles, and two were inoculated with an HA Ag-negative preinfection stool filtrate. One of each pair of chimpanzees was inoculated intravenously, the other orally. One month later both chimpanzees that had received the HA Ag-positive filtrate developed biochemical, histologic, and clinical evidence of acute viral hepatitis. HA Ag particle (27 nm) were detected in their stools by immune electron microscopy; particle shedding followed a pattern similar to that in human volunteers. Immune electron microscopy also showed that antibody HA Ag had developed in the convalescent-phase sera of the infected chimpanzees. Control animals remained free of illness at this time but did develop hepatitis three to five weeks after exposure to the two infected chimpanzee-. The infectious inoculum was titrated in two additional seronegative chimpanzees. It was concluded that hepatitis a can be successfully transmitted to seronegative chimpanzees. Moreover, these studies provide further evidence that the 27-nm virus-like HA Ag particle is the etiologic agent of viral hepatitis type A."} {"id": "PMID:171321", "title": "A prospective evaluation of heterophile and Epstein-Barr virus-specific IgM antibody tests in clinical and subclinical infectious mononucleosis: Specificity and sensitivity of the tests and persistence of antibody.", "content": "Three heterophile antibody tests and a test specific for IgM antibody to Epstein-Barr virus were evaluated during prospective studies of infectious mononucleosis. Specificity was judged by the frequency of false-positive results in sera of known qualities taken before illness; except for two patients bled during early, unrecognized illnes,, titers of greater than or equal to 1:40 were detected in 12% by the absorbed sheep red cell test, in 6.7% by the absorbed horse red cell test, and in none by the beef cell hemolysin test. None had IgM antibody specific for Epstein-Barr virus in sera obtained before illness. In addition, no rises in titer of heterophile antibody were detected by the horse cell test in 38 patients with proved rubella and/or influenza infection. In terms of sensitivity (indicated by the percentage of cases with diagnostic titers during infectious mononucleosis), 97% were positive by the Epstein-Barr virus IgM test, 96% by the horse cell agglutination test, 85% by the beef hemolysin test, and 81% by the sheep cell agglutination test. Persistence of antibody was judged by serial bleedings up to three years after illness; titers of heterophile antibody by the sheep agglutination and beef hemolysin tests as well as titers of IgM antibody to Epstein-Barr virus returned to normal in two to three months, whereas the horse cell heterophile test remained positive for a year or more in 75%. Inapparent and mild infections with Epstein-Barr virus resulted in the production of horse cell heterophile antibody in 48.4% of 122 subjects.", "contents": "A prospective evaluation of heterophile and Epstein-Barr virus-specific IgM antibody tests in clinical and subclinical infectious mononucleosis: Specificity and sensitivity of the tests and persistence of antibody. Three heterophile antibody tests and a test specific for IgM antibody to Epstein-Barr virus were evaluated during prospective studies of infectious mononucleosis. Specificity was judged by the frequency of false-positive results in sera of known qualities taken before illness; except for two patients bled during early, unrecognized illnes,, titers of greater than or equal to 1:40 were detected in 12% by the absorbed sheep red cell test, in 6.7% by the absorbed horse red cell test, and in none by the beef cell hemolysin test. None had IgM antibody specific for Epstein-Barr virus in sera obtained before illness. In addition, no rises in titer of heterophile antibody were detected by the horse cell test in 38 patients with proved rubella and/or influenza infection. In terms of sensitivity (indicated by the percentage of cases with diagnostic titers during infectious mononucleosis), 97% were positive by the Epstein-Barr virus IgM test, 96% by the horse cell agglutination test, 85% by the beef hemolysin test, and 81% by the sheep cell agglutination test. Persistence of antibody was judged by serial bleedings up to three years after illness; titers of heterophile antibody by the sheep agglutination and beef hemolysin tests as well as titers of IgM antibody to Epstein-Barr virus returned to normal in two to three months, whereas the horse cell heterophile test remained positive for a year or more in 75%. Inapparent and mild infections with Epstein-Barr virus resulted in the production of horse cell heterophile antibody in 48.4% of 122 subjects."} {"id": "PMID:171322", "title": "Comparative serial virologic and serologic studies of symptomatic and subclinical congenitally and natally acquired cytomegalovirus infections.", "content": "Infants with congenitally (38) and natally (17) acquired cytomegalovirus infection were prospectively studied by means of virologic and multiple serologic assays. These infections were characterized by chronic viral excretion (measured in years). The quantity of virus excreted in the urine during early infancy was significantly greater in infants who acquired infection in utero, particularly amon those born with overt disease; thereafter, all three groups (congenital symptomatic, congenital asymptomatic, and natal) excreted similar amounts of virus. The patterns of antibody responses, particularly the fluorescent antibody response to the early antigen and the complement-fixing antibody response, further indicated that congenitally infected infants (especially symptomatic ones) bear a greater antigenic burden than do natally infected infants. From a diagnostic standpoint, the test for fluorescent antibody to the late antigen was the most sensitive assay, whereas the test for complement-fixing antibody proved to be the least useful, The indirect hemagglutination assay, although performed only in infants with natal infection, was only slightly less sensitive than the fluorescent antibody procedure; by the former technique, diagnostic rises were detected in all but one infant after the onset of viruria.", "contents": "Comparative serial virologic and serologic studies of symptomatic and subclinical congenitally and natally acquired cytomegalovirus infections. Infants with congenitally (38) and natally (17) acquired cytomegalovirus infection were prospectively studied by means of virologic and multiple serologic assays. These infections were characterized by chronic viral excretion (measured in years). The quantity of virus excreted in the urine during early infancy was significantly greater in infants who acquired infection in utero, particularly amon those born with overt disease; thereafter, all three groups (congenital symptomatic, congenital asymptomatic, and natal) excreted similar amounts of virus. The patterns of antibody responses, particularly the fluorescent antibody response to the early antigen and the complement-fixing antibody response, further indicated that congenitally infected infants (especially symptomatic ones) bear a greater antigenic burden than do natally infected infants. From a diagnostic standpoint, the test for fluorescent antibody to the late antigen was the most sensitive assay, whereas the test for complement-fixing antibody proved to be the least useful, The indirect hemagglutination assay, although performed only in infants with natal infection, was only slightly less sensitive than the fluorescent antibody procedure; by the former technique, diagnostic rises were detected in all but one infant after the onset of viruria."} {"id": "PMID:171323", "title": "Enhanced host defense mechanisms with levamisole in suckling rats.", "content": "Levamisole, a synthetically produced anthelminthic agent, was administered to suckling rats that were challenged with bacterial and viral pathogens. There was no in vitro antibacterial or antiviral effect of the drug. However, enhanced survival was demonstrated in those animals treated with levamisole and challenged with Staphylococcus aureus or herpes simplex virus. The mechanism for protection against the bacteria appears to be enhancement of the primary inflammatory response. The mechanism for protection against herpes simplex virus is not yet understood.", "contents": "Enhanced host defense mechanisms with levamisole in suckling rats. Levamisole, a synthetically produced anthelminthic agent, was administered to suckling rats that were challenged with bacterial and viral pathogens. There was no in vitro antibacterial or antiviral effect of the drug. However, enhanced survival was demonstrated in those animals treated with levamisole and challenged with Staphylococcus aureus or herpes simplex virus. The mechanism for protection against the bacteria appears to be enhancement of the primary inflammatory response. The mechanism for protection against herpes simplex virus is not yet understood."} {"id": "PMID:171324", "title": "Experimental infection of marmosets with a cytomegalovirus of human origin.", "content": "Two adult and two neonatal cotton-topped marmosets and two neonatal white-lipped marmosets (Saguinus species) were inoculated with 10(7) plaque-forming units of cytomegalovirus (Colburn strain). No overt clinical disease developed in four marmosets during observation for eight months; one adult and one neonatal cotton-topped marmoset died from nonspecific causes 63 and 259 days after inoculation, respectively. By days 7-16 after inoculation, all marmosets developed plasma antibodies, which were detectable by neutralization and immunofluorescence assays (peak titers, 1:128-1:256 and 1:64-1:256, respectively). Attempts to isolate virus from whole blood, peripheral lymphocytes, oropharyngeal swabs, or vaginal swabs by cocultivation with permissive cell cultures were unsuccessful. Virus was recovered, however, by cocultivation from the kidney tissues of the adult marmoset that died. Immunosuppressive treatment with azathioprine resulted in a fourfold increase in antibody levels in plasma of two of three marmosets.", "contents": "Experimental infection of marmosets with a cytomegalovirus of human origin. Two adult and two neonatal cotton-topped marmosets and two neonatal white-lipped marmosets (Saguinus species) were inoculated with 10(7) plaque-forming units of cytomegalovirus (Colburn strain). No overt clinical disease developed in four marmosets during observation for eight months; one adult and one neonatal cotton-topped marmoset died from nonspecific causes 63 and 259 days after inoculation, respectively. By days 7-16 after inoculation, all marmosets developed plasma antibodies, which were detectable by neutralization and immunofluorescence assays (peak titers, 1:128-1:256 and 1:64-1:256, respectively). Attempts to isolate virus from whole blood, peripheral lymphocytes, oropharyngeal swabs, or vaginal swabs by cocultivation with permissive cell cultures were unsuccessful. Virus was recovered, however, by cocultivation from the kidney tissues of the adult marmoset that died. Immunosuppressive treatment with azathioprine resulted in a fourfold increase in antibody levels in plasma of two of three marmosets."} {"id": "PMID:171327", "title": "Effects of dichloromethylene diphosphonate, ethane-1-hydroxy-1,1-diphosphonate, and rickets in rats.", "content": "This study compared bone remodeling, bone mineralization, and parathyroid hormone secretion in rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP). The results were compared with findings in rachitic and control rats. In addition, calcification was induced in the skin by administration of lead acetate intravenously and polymyxin B subcutaneously; the efficacies of EHDP and Cl2MDP in preventing the calcific plaque were compared. Both the serum biochemical values and the morphologic findings indicate that Cl2MDP and EHDP influence bone and mineral metabolism differently. Even with the relatively large doses used in this study, Cl2MDP had a minor or no effect while EHDP had a marked effect that, in general, is undersirable. EHDP caused increase in circulating immunoreactive parathyroid hormone to levels greater than those in rachitic rats. Both diphosphonates appear to have a similar effect on the ectopic mineralization produced by calciphylaxis, suggesting that Cl2MDP may be the agent of choice in this problem because the undersirable side-effects would be avoided.", "contents": "Effects of dichloromethylene diphosphonate, ethane-1-hydroxy-1,1-diphosphonate, and rickets in rats. This study compared bone remodeling, bone mineralization, and parathyroid hormone secretion in rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP). The results were compared with findings in rachitic and control rats. In addition, calcification was induced in the skin by administration of lead acetate intravenously and polymyxin B subcutaneously; the efficacies of EHDP and Cl2MDP in preventing the calcific plaque were compared. Both the serum biochemical values and the morphologic findings indicate that Cl2MDP and EHDP influence bone and mineral metabolism differently. Even with the relatively large doses used in this study, Cl2MDP had a minor or no effect while EHDP had a marked effect that, in general, is undersirable. EHDP caused increase in circulating immunoreactive parathyroid hormone to levels greater than those in rachitic rats. Both diphosphonates appear to have a similar effect on the ectopic mineralization produced by calciphylaxis, suggesting that Cl2MDP may be the agent of choice in this problem because the undersirable side-effects would be avoided."} {"id": "PMID:171328", "title": "Hidradenomata of the external auditory meatus. (Review of the literature and report of a pleomorphic adenoma).", "content": "A case of hidradenoma of the external auditory meatus ('ceruminoma') is presented, with a review of the literature. The tumour has the appearances of a pleomorphic adenoma and is devoid of a capsule. It is suggested that the term hidradenoma be used for tumours of the ceruminous glands and that they be classified histologically as (1) adenoma, (2) pleomorphic adenoma, (3) adenoid cystic carcinoma and (4) adenocarcinoma. This classification aids treatment and prognosis. Attention is drawn to the high incidence of malignancy in hidradenomata of the external auditory meatus. The treatment of choice for pleomorphic adenomata is wide surgical excision with an adequate margin of normal skin. If there is doubt regarding complete removal, or a recurrence develops, a wider surgical excision is necessitated.", "contents": "Hidradenomata of the external auditory meatus. (Review of the literature and report of a pleomorphic adenoma). A case of hidradenoma of the external auditory meatus ('ceruminoma') is presented, with a review of the literature. The tumour has the appearances of a pleomorphic adenoma and is devoid of a capsule. It is suggested that the term hidradenoma be used for tumours of the ceruminous glands and that they be classified histologically as (1) adenoma, (2) pleomorphic adenoma, (3) adenoid cystic carcinoma and (4) adenocarcinoma. This classification aids treatment and prognosis. Attention is drawn to the high incidence of malignancy in hidradenomata of the external auditory meatus. The treatment of choice for pleomorphic adenomata is wide surgical excision with an adequate margin of normal skin. If there is doubt regarding complete removal, or a recurrence develops, a wider surgical excision is necessitated."} {"id": "PMID:171331", "title": "Responses of hair cells to statocyst rotation.", "content": "A new technique is described for stimulating hair cells of the Hermissenda statocyst. The preparation and recording apparatus can be rotated at up to 78 rpm while recording intracellular potentials. Hair cells in front of the centrifugal force vector depolarize in response to rotation. Hair cells in back of the centrifugal force vector hypoerpolarize in response to rotation. Mechanisms by which the hair cell generator potential might arise are examined.", "contents": "Responses of hair cells to statocyst rotation. A new technique is described for stimulating hair cells of the Hermissenda statocyst. The preparation and recording apparatus can be rotated at up to 78 rpm while recording intracellular potentials. Hair cells in front of the centrifugal force vector depolarize in response to rotation. Hair cells in back of the centrifugal force vector hypoerpolarize in response to rotation. Mechanisms by which the hair cell generator potential might arise are examined."} {"id": "PMID:171332", "title": "Adaptation of N-tropic Friend leukaemia virus and its murine sarcoma virus pseudotype of non-permissive B-type C57BL/6 mouse cell line.", "content": "N-tropic Friend leukaemia virus (FLV) was serially passaged in a B-type C57BL/6 mouse cell line, YH-7. After a single passage, the infectious efficiency of FLV in the restrictive YH-7 cells was significantly increased. This adapted character of FLV could be reversed by a single passage in permissive N-type MLg cells. The true host range conversion from N to NB was accomplished after eleven to twelve passages in YH-7 cells. In contrast, the host range conversion of N-tropic murine sarcoma pseudotype, MuSV(FLV), took place after two passages.", "contents": "Adaptation of N-tropic Friend leukaemia virus and its murine sarcoma virus pseudotype of non-permissive B-type C57BL/6 mouse cell line. N-tropic Friend leukaemia virus (FLV) was serially passaged in a B-type C57BL/6 mouse cell line, YH-7. After a single passage, the infectious efficiency of FLV in the restrictive YH-7 cells was significantly increased. This adapted character of FLV could be reversed by a single passage in permissive N-type MLg cells. The true host range conversion from N to NB was accomplished after eleven to twelve passages in YH-7 cells. In contrast, the host range conversion of N-tropic murine sarcoma pseudotype, MuSV(FLV), took place after two passages."} {"id": "PMID:171333", "title": "Attempts to extend the genetic map of poliovirus temperature-sensitive mutants.", "content": "Eighteen new ts mutants of poliovirus have been isolated after a variety of mutagenic treatments, and their loci identified in relation to the previous genetic map. The map was only extended by 25%, and the physiological characters of the new isolates corresponded in all aspects tested with those of the previous isolates. Apparently single mutants at the extreme left of the map were defective in synthesis of both double- and single-stranded RNA, functions that do not co-vary in other mutants. Two procedures respectively predicted to induce mutations preferentially in the 5' and 3' regions of the genome gave isolates which all indicated that the structural protein region was nearest the 5' end. The loci fro resistance to dextran sulphate and to ethyl-2-methylthio-4-methyl-5-pyrimidine carboxylate both lie in the structural protein region.", "contents": "Attempts to extend the genetic map of poliovirus temperature-sensitive mutants. Eighteen new ts mutants of poliovirus have been isolated after a variety of mutagenic treatments, and their loci identified in relation to the previous genetic map. The map was only extended by 25%, and the physiological characters of the new isolates corresponded in all aspects tested with those of the previous isolates. Apparently single mutants at the extreme left of the map were defective in synthesis of both double- and single-stranded RNA, functions that do not co-vary in other mutants. Two procedures respectively predicted to induce mutations preferentially in the 5' and 3' regions of the genome gave isolates which all indicated that the structural protein region was nearest the 5' end. The loci fro resistance to dextran sulphate and to ethyl-2-methylthio-4-methyl-5-pyrimidine carboxylate both lie in the structural protein region."} {"id": "PMID:171334", "title": "On the use of chloramine-T to iodinate specifically the surface proteins of intact enveloped viruses.", "content": "Rous-associated virus-6I was used as a model for studying the labelling specificity of the chloramine-T iodination procedure when applied to intact enveloped viruses. The specificity of labelling depended markedly on the concentration of iodide in the reaction mixture. At low concentrations of iodide (below 0-5 muM) only the surface proteins and lipid of intact virions were iodinated; there was no detectable labelling of internal proteins. At 10 muM-iodide, however, both internal and external proteins were iodinated; moreover there was a marked change in the reactivity of the surface proteins. It appears that the lipid envelope provides an effective barrier to the iodinating complex generated at low, but not at high, concentrations of iodide. These and other observations suggest that the chloramine-T procedure has a previously unrecognized potential for specifically labelling the surface proteins of lipid-enveloped structures.", "contents": "On the use of chloramine-T to iodinate specifically the surface proteins of intact enveloped viruses. Rous-associated virus-6I was used as a model for studying the labelling specificity of the chloramine-T iodination procedure when applied to intact enveloped viruses. The specificity of labelling depended markedly on the concentration of iodide in the reaction mixture. At low concentrations of iodide (below 0-5 muM) only the surface proteins and lipid of intact virions were iodinated; there was no detectable labelling of internal proteins. At 10 muM-iodide, however, both internal and external proteins were iodinated; moreover there was a marked change in the reactivity of the surface proteins. It appears that the lipid envelope provides an effective barrier to the iodinating complex generated at low, but not at high, concentrations of iodide. These and other observations suggest that the chloramine-T procedure has a previously unrecognized potential for specifically labelling the surface proteins of lipid-enveloped structures."} {"id": "PMID:171335", "title": "The polypeptide structure of transmissible gastroenteritis virus.", "content": "The polypeptides of purified preparations of the coronavirus responsible for transmissible gastroenteritis of pigs have beem examined by polyacrylamide gel electrophoresis. Four major polypeptides, VPI (mol. wt. 200000), VP2 (50 000), VP3 (30000) and VP4 (28500) and two minor polypeptides, VPIa (105000) and VPIb (80500) have been reproducibly demonstrated in the virion, of which VPI, VP3 and VP4 contain carbohydrate. Treatment of the virion with the proteolytic enzyme bromelain removes the surface projections and VPI, thus identifying this glycopolypeptide as the major structural component of the projection.", "contents": "The polypeptide structure of transmissible gastroenteritis virus. The polypeptides of purified preparations of the coronavirus responsible for transmissible gastroenteritis of pigs have beem examined by polyacrylamide gel electrophoresis. Four major polypeptides, VPI (mol. wt. 200000), VP2 (50 000), VP3 (30000) and VP4 (28500) and two minor polypeptides, VPIa (105000) and VPIb (80500) have been reproducibly demonstrated in the virion, of which VPI, VP3 and VP4 contain carbohydrate. Treatment of the virion with the proteolytic enzyme bromelain removes the surface projections and VPI, thus identifying this glycopolypeptide as the major structural component of the projection."} {"id": "PMID:171336", "title": "Two levels of restriction by mouse or cat cells of murine sarcoma virus coated by endogenous xenotropic oncornavirus.", "content": "Mouse and cat cells were each examined for the mode of restriction of endogenous xenotropic oncornavirus. Murine xenotropic helper virus (MuX) and its pseudo-type of Moloney murine sarcoma virus (MSV(MuX)) were grown in cat cells to high titre. MuX alone did not replicate in any mouse cell tested including normal or transformed outbred Swis 3T3 cells or SC-I cells, but did grow in a variety of other mammalian cells. MSV(MuX) was not able to achieve that intracellular state from which it could be rescued by mouse leukaemia virus (MuLV) in any mouse cell tested with the exception of SC-I cells. Detection of MSV(MuX) foci with appropriate helper virus was as sensitive in SC-I cells as in the cells of several other species. Sequential passage of MSV(MuX) virus complex in SC=I cells resulted in a loss of infectious sarcoma and helper viruses, but transformed, MSV rescuable cells were retained. If cat embryo cells were infected with either the feline endogenous xenotropic virus (FeX) or its MSV pseudotype (MSV(FeX), two analogous states of restriction were observed. FeX alone did not replicate in cat cells as measured by release of progeny virus or by FeX group-specific antigen induction. Cat cells could be susceptible or insusceptible to the entry of MSV(FeX) as measured by MSV rescue with appropriate ecotropic feline leukaemia virus. The sensitivity of detection of MSV(FeX) foci in some cat cells in the presence of feline ecotropic virus was comparable to that exhibited by cells of other mammalian species. A single strain of cat cells underwent a change in its restrictive capacity for MSV(FeX) on prolonged passage. Late passage cat cells became very insusceptible to MSV(FeX) but not to other pseudotypes of MSV. Infectious FeX or its group-specific antigens were not detected in the insusceptible cells. The major glycoprotein of FeX did appear as a surface antigen of the insusceptibel cells. It is apparent that two levels of cellular restriction can be distinguished in each of two mammalian cell systems by the susceptibility to penetration of MSV coated with endogenous xenotropic oncornavirus.", "contents": "Two levels of restriction by mouse or cat cells of murine sarcoma virus coated by endogenous xenotropic oncornavirus. Mouse and cat cells were each examined for the mode of restriction of endogenous xenotropic oncornavirus. Murine xenotropic helper virus (MuX) and its pseudo-type of Moloney murine sarcoma virus (MSV(MuX)) were grown in cat cells to high titre. MuX alone did not replicate in any mouse cell tested including normal or transformed outbred Swis 3T3 cells or SC-I cells, but did grow in a variety of other mammalian cells. MSV(MuX) was not able to achieve that intracellular state from which it could be rescued by mouse leukaemia virus (MuLV) in any mouse cell tested with the exception of SC-I cells. Detection of MSV(MuX) foci with appropriate helper virus was as sensitive in SC-I cells as in the cells of several other species. Sequential passage of MSV(MuX) virus complex in SC=I cells resulted in a loss of infectious sarcoma and helper viruses, but transformed, MSV rescuable cells were retained. If cat embryo cells were infected with either the feline endogenous xenotropic virus (FeX) or its MSV pseudotype (MSV(FeX), two analogous states of restriction were observed. FeX alone did not replicate in cat cells as measured by release of progeny virus or by FeX group-specific antigen induction. Cat cells could be susceptible or insusceptible to the entry of MSV(FeX) as measured by MSV rescue with appropriate ecotropic feline leukaemia virus. The sensitivity of detection of MSV(FeX) foci in some cat cells in the presence of feline ecotropic virus was comparable to that exhibited by cells of other mammalian species. A single strain of cat cells underwent a change in its restrictive capacity for MSV(FeX) on prolonged passage. Late passage cat cells became very insusceptible to MSV(FeX) but not to other pseudotypes of MSV. Infectious FeX or its group-specific antigens were not detected in the insusceptible cells. The major glycoprotein of FeX did appear as a surface antigen of the insusceptibel cells. It is apparent that two levels of cellular restriction can be distinguished in each of two mammalian cell systems by the susceptibility to penetration of MSV coated with endogenous xenotropic oncornavirus."} {"id": "PMID:171337", "title": "'Phagocytosis' of sendai virus by model membranes.", "content": "Sendai viruses were attached to liposomes (vesicular model membranes) at 0 to 4 degrees C, and were then incubated at 37 degrees C. Liposomes made of phosphatidylcholine, cholesterol and gangliosides enveloped the viruses at 37 degrees C to give a picture that resembles the ingestion step of phagocytosis. Virus particles were enveloped only by liposomes that contained gangliosides which serve as Sendai virus receptors.", "contents": "'Phagocytosis' of sendai virus by model membranes. Sendai viruses were attached to liposomes (vesicular model membranes) at 0 to 4 degrees C, and were then incubated at 37 degrees C. Liposomes made of phosphatidylcholine, cholesterol and gangliosides enveloped the viruses at 37 degrees C to give a picture that resembles the ingestion step of phagocytosis. Virus particles were enveloped only by liposomes that contained gangliosides which serve as Sendai virus receptors."} {"id": "PMID:171338", "title": "Regulation by thymidine monophosphate and other nucleotides of thymidine kinase activity in extracts from primary rabbit kidney cells infected by HSV types 1 and 2.", "content": "In an attempt to differentiate between thymidine kinase (EC.2.4.1.21) induced by herpesvirus hominis type I (TK I) and type 2 (TK2), the different susceptibilities to the modifying effects of some thymidine analogues proved to be useful criteria: (I)2'-deoxythymidine-5'-triphosphate (dThd-5'-PPP) inhibits TK 2 at a concentration of 0-125 mM by 90%, whereas TK I is inhibited at 4-03 mM by 50%. (2) 2'-deoxythymidine-5'-monophosphate (dThd-5'-P) competitively inhibits TK 2 at all concentrations tested. On the other hand, the direction of its effect on TK I is concentration dependent: at 500 mum it stimulates and at 8 mM inhibits TK I activity. During enzyme kinetic studies, TK I displays substrate inhibition which is reversed by dThd-5'-P. This result explains the stimulating effect of dThd-5'-P at 500 muM. This phenomenon suggests the existence on the enzyme molecule of a second binding site for dThd which mediates substrate inhibition and which can be occupied also by dThd-5'-P. After polyacrylamide gel electrophoresis of TK I, the stimulation by dThd-5'-P disappears, suggesting the separation of the second binding site from the catalytic centre.", "contents": "Regulation by thymidine monophosphate and other nucleotides of thymidine kinase activity in extracts from primary rabbit kidney cells infected by HSV types 1 and 2. In an attempt to differentiate between thymidine kinase (EC.2.4.1.21) induced by herpesvirus hominis type I (TK I) and type 2 (TK2), the different susceptibilities to the modifying effects of some thymidine analogues proved to be useful criteria: (I)2'-deoxythymidine-5'-triphosphate (dThd-5'-PPP) inhibits TK 2 at a concentration of 0-125 mM by 90%, whereas TK I is inhibited at 4-03 mM by 50%. (2) 2'-deoxythymidine-5'-monophosphate (dThd-5'-P) competitively inhibits TK 2 at all concentrations tested. On the other hand, the direction of its effect on TK I is concentration dependent: at 500 mum it stimulates and at 8 mM inhibits TK I activity. During enzyme kinetic studies, TK I displays substrate inhibition which is reversed by dThd-5'-P. This result explains the stimulating effect of dThd-5'-P at 500 muM. This phenomenon suggests the existence on the enzyme molecule of a second binding site for dThd which mediates substrate inhibition and which can be occupied also by dThd-5'-P. After polyacrylamide gel electrophoresis of TK I, the stimulation by dThd-5'-P disappears, suggesting the separation of the second binding site from the catalytic centre."} {"id": "PMID:171339", "title": "The site of anoxic block in the spinal monosynaptic pathway.", "content": "Asphyxiation of the spinal cord for periods of 2-4 min leads to block of the monosynaptic pathway. At about the same time this blockage takes place, the afferent action potentials fail to invade the presynaptic terminals. Asphyxiation also interferes with the antidromic invasion of motoneurons, and the failure of the antidromic action potentials to invade the motoneuron dendrites coincides with the time of the disappearance of the orthodromic monosynaptic responses. During reoxygenation, both the presynaptic terminals and the dendrites recover their function, or rather their polarization, in a few seconds and yet synaptic transmission reappears only after several minutes. It is postulated that failure of synaptic transmission during asphyxia is due to depolarization of both the presynaptic terminals and the dendrites of the postsynaptic elements. However, repolarization of these elements during reoxygenation, is not sufficient to reestablish synaptic transmission, but recovery of some unidentified biochemical process is apparently necessary.", "contents": "The site of anoxic block in the spinal monosynaptic pathway. Asphyxiation of the spinal cord for periods of 2-4 min leads to block of the monosynaptic pathway. At about the same time this blockage takes place, the afferent action potentials fail to invade the presynaptic terminals. Asphyxiation also interferes with the antidromic invasion of motoneurons, and the failure of the antidromic action potentials to invade the motoneuron dendrites coincides with the time of the disappearance of the orthodromic monosynaptic responses. During reoxygenation, both the presynaptic terminals and the dendrites recover their function, or rather their polarization, in a few seconds and yet synaptic transmission reappears only after several minutes. It is postulated that failure of synaptic transmission during asphyxia is due to depolarization of both the presynaptic terminals and the dendrites of the postsynaptic elements. However, repolarization of these elements during reoxygenation, is not sufficient to reestablish synaptic transmission, but recovery of some unidentified biochemical process is apparently necessary."} {"id": "PMID:171340", "title": "Seizure susceptibility in the developing mouse and its relationship to glutamate decarboxylase and pyridoxal phosphate in brain.", "content": "The relationship between the susceptibility to convulsions, the content of pyridoxal 5'-phosphate and the activity of pyridoxal kinase (EC 2.7.1.35) and glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse. Seizures were induced by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH), a drug previously reported to reduce the levels of pyridoxal 5'-phosphate and as a consequence to inhibit the activity of glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain, pyridoxal kinase activity and pyridoxal 5'-phosphate levels were decreased by the administration of PLPGH at all ages studied, whereas glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of glutamate decarboxylase by pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to seizures induced by PLPGH during development is probably related to the increase observed in the sensitivity of glutamate decarboxylase in vivo to a decrease of pyridoxal 5'-phosphate levels. The correlation between pyridoxal 5'-phosphate, glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age.", "contents": "Seizure susceptibility in the developing mouse and its relationship to glutamate decarboxylase and pyridoxal phosphate in brain. The relationship between the susceptibility to convulsions, the content of pyridoxal 5'-phosphate and the activity of pyridoxal kinase (EC 2.7.1.35) and glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse. Seizures were induced by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH), a drug previously reported to reduce the levels of pyridoxal 5'-phosphate and as a consequence to inhibit the activity of glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain, pyridoxal kinase activity and pyridoxal 5'-phosphate levels were decreased by the administration of PLPGH at all ages studied, whereas glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of glutamate decarboxylase by pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to seizures induced by PLPGH during development is probably related to the increase observed in the sensitivity of glutamate decarboxylase in vivo to a decrease of pyridoxal 5'-phosphate levels. The correlation between pyridoxal 5'-phosphate, glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age."} {"id": "PMID:171341", "title": "Phenothiazine antagonism of the noradrenergic inhibition of cerebellar Purkinje neurons.", "content": "Phenothiazine derivatives were examined as potential antagonists of the inhibitory noradrenergic synapses from the nucleus locus coeruleus to rat cerebellar Purkinje cells. Fluphenazine, and its thioxanthine analogue, flupenthixol, antagonized the inhibitory action of norepinephrine, when iontrophoretically applied to single cells. Alpha-flupenthixol was generally more active than the beta isomer. Fluphenazine had no appreciable effect on inhibitions induced by iontophoresis of GABA or cyclic AMP. Parenteral fluphenazine also blocked the inhibition of Purkinje cells produced by the stimulation of the noradrenergic pathway from locus coeruleus, but basket and stellate cell inhibitory inputs to Purkinje cells were unaffected. These data suggest that fluphenazine can specifically block a known central adrenergic inhibitory pathway.", "contents": "Phenothiazine antagonism of the noradrenergic inhibition of cerebellar Purkinje neurons. Phenothiazine derivatives were examined as potential antagonists of the inhibitory noradrenergic synapses from the nucleus locus coeruleus to rat cerebellar Purkinje cells. Fluphenazine, and its thioxanthine analogue, flupenthixol, antagonized the inhibitory action of norepinephrine, when iontrophoretically applied to single cells. Alpha-flupenthixol was generally more active than the beta isomer. Fluphenazine had no appreciable effect on inhibitions induced by iontophoresis of GABA or cyclic AMP. Parenteral fluphenazine also blocked the inhibition of Purkinje cells produced by the stimulation of the noradrenergic pathway from locus coeruleus, but basket and stellate cell inhibitory inputs to Purkinje cells were unaffected. These data suggest that fluphenazine can specifically block a known central adrenergic inhibitory pathway."} {"id": "PMID:171342", "title": "Neuromuscular junctions in the buccal mass of Aplysia: fine structure and electrophysiology of excitatory transmission.", "content": "The lower extrinsic protractor muscle in the buccal mass of Aplysia consists of bundles of muscle fibers 4--12 mu in diameter, containing thick and thin filaments that are not arranged in a transversely striated pattern. Individual fibers come close to one another and form specialized junctional regions. Electrophysiological evidence indicates that the muscle fibers form an electrical cyncytium. Muscle bundles are innervated by more than one excitatory axon at a number of points along their length. The presynaptic terminals contain spherical electron-lucent vesicles and a few larger electron-dense vesicles. There are no obvious structural postsynaptic specializations. Graded contraction can result from summation of excitatory junctional potentials in separate axons or from summation and facilitation of junctional potentials from a single axon. The buildup of facilitation during a train of stimuli results from the linear summation of facilitation remaining from preceding impulses.", "contents": "Neuromuscular junctions in the buccal mass of Aplysia: fine structure and electrophysiology of excitatory transmission. The lower extrinsic protractor muscle in the buccal mass of Aplysia consists of bundles of muscle fibers 4--12 mu in diameter, containing thick and thin filaments that are not arranged in a transversely striated pattern. Individual fibers come close to one another and form specialized junctional regions. Electrophysiological evidence indicates that the muscle fibers form an electrical cyncytium. Muscle bundles are innervated by more than one excitatory axon at a number of points along their length. The presynaptic terminals contain spherical electron-lucent vesicles and a few larger electron-dense vesicles. There are no obvious structural postsynaptic specializations. Graded contraction can result from summation of excitatory junctional potentials in separate axons or from summation and facilitation of junctional potentials from a single axon. The buildup of facilitation during a train of stimuli results from the linear summation of facilitation remaining from preceding impulses."} {"id": "PMID:171343", "title": "Soradic ulcerative mutilating acropathy with imbalance of free amino acids in the cerebrospinal fluid.", "content": "A case of sporadic ulcerative mutilating acropathy is described. Muscle biopsy showed signs of neurogenic atrophy. Motor nerve conduction velocity was slightly reduced. The muscles of the foot were completely unresponsive to electric stimulation of both femoral nerves. The content of free amino acids in serum and cerebrospinal fluid was determined by ion exchange chromatography, and compared with a control group. While in serum no significant changes were found, in CSF most amino acids showed great alterations, mainly consisting in an increase. It is suggested that the primary disturbance may be located in the spinal nerve roots.", "contents": "Soradic ulcerative mutilating acropathy with imbalance of free amino acids in the cerebrospinal fluid. A case of sporadic ulcerative mutilating acropathy is described. Muscle biopsy showed signs of neurogenic atrophy. Motor nerve conduction velocity was slightly reduced. The muscles of the foot were completely unresponsive to electric stimulation of both femoral nerves. The content of free amino acids in serum and cerebrospinal fluid was determined by ion exchange chromatography, and compared with a control group. While in serum no significant changes were found, in CSF most amino acids showed great alterations, mainly consisting in an increase. It is suggested that the primary disturbance may be located in the spinal nerve roots."} {"id": "PMID:171344", "title": "Experimental neuropathy produced by 2,5-hexanedione--a major metabolite of the neurotoxic industrial solvent methyl n-butyl ketone.", "content": "Chronic exposure of rats to 2,5-hexanedione (CH3COCH2CH2COCH3), a major metabolite of the neurotoxic industrial solvent methyl n-buryl ketone (CH3COCH2CH2CH2CH3), has been shown to cause a clinical peripheral neuropathy with dying-back peripheral and central nervous system degeneration characterized by giant axonal swellings filled with neurofilaments. This pattern of disease is similar to that produced by methyl n-butyl ketone.", "contents": "Experimental neuropathy produced by 2,5-hexanedione--a major metabolite of the neurotoxic industrial solvent methyl n-butyl ketone. Chronic exposure of rats to 2,5-hexanedione (CH3COCH2CH2COCH3), a major metabolite of the neurotoxic industrial solvent methyl n-buryl ketone (CH3COCH2CH2CH2CH3), has been shown to cause a clinical peripheral neuropathy with dying-back peripheral and central nervous system degeneration characterized by giant axonal swellings filled with neurofilaments. This pattern of disease is similar to that produced by methyl n-butyl ketone."} {"id": "PMID:171345", "title": "Safety factor in single human motor end-plates studied in vivo with single fibre electromyography.", "content": "In a single fibre EMG investigation on healthy subjects the relationship between the neuromuscular jitter and the safety factor of the motor end-plate relative to curare was studied. A positive correlation was found between the jitter increase after a standard dose of D-tubocurarine and the initial jitter. The conclusion was drawn that the neuromuscular jitter can be used as an indicator of the safety factor. There are a number of nerve-muscle disorders in which the jitter is increased, probably indicating a reduced safety factor which may be of clinical importance when these patients are subjected to diseases or drugs which would otherwise not produce neuromuscular symptomatology.", "contents": "Safety factor in single human motor end-plates studied in vivo with single fibre electromyography. In a single fibre EMG investigation on healthy subjects the relationship between the neuromuscular jitter and the safety factor of the motor end-plate relative to curare was studied. A positive correlation was found between the jitter increase after a standard dose of D-tubocurarine and the initial jitter. The conclusion was drawn that the neuromuscular jitter can be used as an indicator of the safety factor. There are a number of nerve-muscle disorders in which the jitter is increased, probably indicating a reduced safety factor which may be of clinical importance when these patients are subjected to diseases or drugs which would otherwise not produce neuromuscular symptomatology."} {"id": "PMID:171346", "title": "Regional curare for the reduction of the safety factor in human motor end-plates studied with single fibre electromyography.", "content": "A method employing six minutes of regional curarization with 0.5 mg D-tubocurarine and single fibre electromyographic measurements (SFEMG) was used in order to study the effect of an additional small dose of D-tubocurarine. The effect of the additional dose was most pronounced in terms of increased jitter, on motor end-plates with the initially highest jitter. The combination of regional curarization and SFEMG jitter recordings offers a sensitive technique for detecting mild effects of various drugs on neuromuscular transmission not detectable with decrement investigations.", "contents": "Regional curare for the reduction of the safety factor in human motor end-plates studied with single fibre electromyography. A method employing six minutes of regional curarization with 0.5 mg D-tubocurarine and single fibre electromyographic measurements (SFEMG) was used in order to study the effect of an additional small dose of D-tubocurarine. The effect of the additional dose was most pronounced in terms of increased jitter, on motor end-plates with the initially highest jitter. The combination of regional curarization and SFEMG jitter recordings offers a sensitive technique for detecting mild effects of various drugs on neuromuscular transmission not detectable with decrement investigations."} {"id": "PMID:171347", "title": "Single fibre EMG findings in polyneuropathies of different aetiology.", "content": "Single fibre electromyography was carried out in patients with polyneuropathy due to uraemia, diabetes, and alcohol. In the two former groups the fibre density within the motor unit and the impulse transmission were mainly normal. In the latter group the fibre density was significantly increased as signs of reinnervation. Impulse transmission was impaired in a number of the action potential complexes, which is typical of active reinnervation. The results may indicate that the diabetic and uraemic polyneuropathies are characterized in the main by demyelination, whereas the alcoholic type is dominated by axonal lesion even at an early stage.", "contents": "Single fibre EMG findings in polyneuropathies of different aetiology. Single fibre electromyography was carried out in patients with polyneuropathy due to uraemia, diabetes, and alcohol. In the two former groups the fibre density within the motor unit and the impulse transmission were mainly normal. In the latter group the fibre density was significantly increased as signs of reinnervation. Impulse transmission was impaired in a number of the action potential complexes, which is typical of active reinnervation. The results may indicate that the diabetic and uraemic polyneuropathies are characterized in the main by demyelination, whereas the alcoholic type is dominated by axonal lesion even at an early stage."} {"id": "PMID:171348", "title": "5-Hydroxytryptophan and sleep in Down's syndrome.", "content": "Polygraphic total night sleep electroencephalographic (EEG), electro-oculographic (EOG) and electromyographic (EMG) recordings have been made in 6 mongoloid infants who received oral 5-HTP for periods extending from 12 to 36 months. The doses were adapted to the infants' age and tolerance level. The oculomotor activity of paradoxical sleep (PS) was selectively analysed. The eye-movement (EM) density was significantly decreased in non-treated mongoloids as compared with that of normal age-related infants. Out of the 5-HTP-treated patients, however, the results in only 2 were within the limits for normal age-related infants. 5-HTP failed to induce any long-term differences in the EM frequencies. In fact, the drug had a short-term effect lasting up to 8 days. An increase in muscle tone and an improvement of motor behaviour were the only long-lasting results.", "contents": "5-Hydroxytryptophan and sleep in Down's syndrome. Polygraphic total night sleep electroencephalographic (EEG), electro-oculographic (EOG) and electromyographic (EMG) recordings have been made in 6 mongoloid infants who received oral 5-HTP for periods extending from 12 to 36 months. The doses were adapted to the infants' age and tolerance level. The oculomotor activity of paradoxical sleep (PS) was selectively analysed. The eye-movement (EM) density was significantly decreased in non-treated mongoloids as compared with that of normal age-related infants. Out of the 5-HTP-treated patients, however, the results in only 2 were within the limits for normal age-related infants. 5-HTP failed to induce any long-term differences in the EM frequencies. In fact, the drug had a short-term effect lasting up to 8 days. An increase in muscle tone and an improvement of motor behaviour were the only long-lasting results."} {"id": "PMID:171349", "title": "An immunopathologic component in experimental togavirus encephalitis.", "content": "The effects of immune manipulation upon survival and histopathology in two experimental group B togavirus encephalitides were studied in inbred mice. The median survival time 8 days after intracerebral injection of Langat virus increased to 10 days with an immunosuppressive course of cyclophosphamide, with concomitant reduction in the inflammatory response. Adoptive immunization with immune lymphoid cells or serum also tended to prolong Langat virus survival while increasing inflammation. Survival following intracerebral West Nile virus (7 days) was unaffected by immunosuppression or adoptive transfer, although suppression was associated with less severe CNS lesions, and immune serum with less necrosis. These findings indicate that the immune response may be both protective and pathology-inducing in some togarvirus encephalitides. The differences in host response to these two related agents suggest caution in generalizing about the role of the immune response in viral infections.", "contents": "An immunopathologic component in experimental togavirus encephalitis. The effects of immune manipulation upon survival and histopathology in two experimental group B togavirus encephalitides were studied in inbred mice. The median survival time 8 days after intracerebral injection of Langat virus increased to 10 days with an immunosuppressive course of cyclophosphamide, with concomitant reduction in the inflammatory response. Adoptive immunization with immune lymphoid cells or serum also tended to prolong Langat virus survival while increasing inflammation. Survival following intracerebral West Nile virus (7 days) was unaffected by immunosuppression or adoptive transfer, although suppression was associated with less severe CNS lesions, and immune serum with less necrosis. These findings indicate that the immune response may be both protective and pathology-inducing in some togarvirus encephalitides. The differences in host response to these two related agents suggest caution in generalizing about the role of the immune response in viral infections."} {"id": "PMID:171350", "title": "Nuroaxonal degeneration induced by sodium diethyldithiocarbamate in cultures of central nervous tissue.", "content": "Well myelinated cultures of newborn mouse cerebellum, exposed to varying concentrations of sodium diethyldithiocarbamate (DDC), a heavy metal chelating agent, were examined by light and electron microscopy. DDC treatment of cultures for 24-48 hours produced swellings of axons and presynaptic endings, the morphological features characteristic of dystrophic axons. The axonal swellings contained an increased amount of endoplasmic reticulum, mitochondria and dense bodies. A continued exposure to DDC induced an extensive degeneration of axons and ensheathing myelin. Glial cells, on the other hand, were structurally intact even after a long-term exposure to DDC. It is suggested that DDC produces in myelinated CNS cultures an initial enlargement of axons and presynaptic endings and then continues to induce Wallerian degeneration in axons.", "contents": "Nuroaxonal degeneration induced by sodium diethyldithiocarbamate in cultures of central nervous tissue. Well myelinated cultures of newborn mouse cerebellum, exposed to varying concentrations of sodium diethyldithiocarbamate (DDC), a heavy metal chelating agent, were examined by light and electron microscopy. DDC treatment of cultures for 24-48 hours produced swellings of axons and presynaptic endings, the morphological features characteristic of dystrophic axons. The axonal swellings contained an increased amount of endoplasmic reticulum, mitochondria and dense bodies. A continued exposure to DDC induced an extensive degeneration of axons and ensheathing myelin. Glial cells, on the other hand, were structurally intact even after a long-term exposure to DDC. It is suggested that DDC produces in myelinated CNS cultures an initial enlargement of axons and presynaptic endings and then continues to induce Wallerian degeneration in axons."} {"id": "PMID:171351", "title": "Cerebral dynamic studies for early detection of recurrent anaplastic intracranial gliomas.", "content": "The authors compared radionuclide cerebral dynamic studies, brain scans, and clinical evaluation as indicators of recurrence of intracranial anaplastic gliomas and found cerebral dynamic studies more sensitive to tumor growth than static brain scans. The former may show changes prior to clinical evidence of tumor progression.", "contents": "Cerebral dynamic studies for early detection of recurrent anaplastic intracranial gliomas. The authors compared radionuclide cerebral dynamic studies, brain scans, and clinical evaluation as indicators of recurrence of intracranial anaplastic gliomas and found cerebral dynamic studies more sensitive to tumor growth than static brain scans. The former may show changes prior to clinical evidence of tumor progression."} {"id": "PMID:171352", "title": "Central functional changes after facial-spinal-accessory anastomosis in man and facial-hypoglossal anastomosis in the cat.", "content": "A left facial-spinal-accessory anastomosis was performed for peripheral facial paralysis in an 8-year-old boy. By the fourth postoperative year, the corneal reflex showed a normal latency, and left arm and face movements could be executed independently. The possibility of neural plasticity playing a role in establishing new central relationships which enable the achievement of a \"normal\" latency corneal reflex and independent face and arm movements is discussed. The latency of the corneal reflex recorded as electrical response of the orbicularis oculi muscle to electrical stimulation of the ipsilateral cornea was measured in normal cats and cats which had undergone a facial-hypoglossal anastomosis 12 to 14 months previously. The latency of the reflex was 8 to 22 msec in normal animals and 200 to 300 msec in the operated cats, while conduction times in the regenerated hypoglossal nerve fibers were found to be within normal limits. This suggests that the long latency of the corneal reflex following the cross anastomosis is due to the time required for transmission across newly-formed connections between the trigeminal terminals and the hypoglossal neurons.", "contents": "Central functional changes after facial-spinal-accessory anastomosis in man and facial-hypoglossal anastomosis in the cat. A left facial-spinal-accessory anastomosis was performed for peripheral facial paralysis in an 8-year-old boy. By the fourth postoperative year, the corneal reflex showed a normal latency, and left arm and face movements could be executed independently. The possibility of neural plasticity playing a role in establishing new central relationships which enable the achievement of a \"normal\" latency corneal reflex and independent face and arm movements is discussed. The latency of the corneal reflex recorded as electrical response of the orbicularis oculi muscle to electrical stimulation of the ipsilateral cornea was measured in normal cats and cats which had undergone a facial-hypoglossal anastomosis 12 to 14 months previously. The latency of the reflex was 8 to 22 msec in normal animals and 200 to 300 msec in the operated cats, while conduction times in the regenerated hypoglossal nerve fibers were found to be within normal limits. This suggests that the long latency of the corneal reflex following the cross anastomosis is due to the time required for transmission across newly-formed connections between the trigeminal terminals and the hypoglossal neurons."} {"id": "PMID:171355", "title": "A qualitative and quantitative electronmicroscopic study of the structure of the adenoid cystic carcinoma of human minor salivary glands.", "content": "The fine structural characteristics of five adenoid cystic carcinomas of human minor salivary galnds and a quantitative assessment of the relative volumes occupied by morphologically defined cell types in these tumors are reported. We observed that the cyst-like spaces which give the characteristic cribriform pattern to the adenoid cystic carcinoma contain replicated basement membrane-like materail. Material comprisimg aggregates of fine tubules having a median diameter of 270 A, and rounded, electron dense bodies were noted within duct-like lumena of one tumor. In addition, dilatation of the intercellular spaces and squamous metaplasia were noted. From 500 electronmicrographs obtained by standardized techniques and used for the morphological part of the study, 175 were selected by a random sampling method and analyzed by the stereological technique of point counting. This method demonstrated that duct type cells occupied 75% by volume of the tumor in these glands; myoepithelial cells occupied 3%, acinar cells occupied 2%, and other tissues occupied 22% of the tumors. These proportions differ significantly (P less than 0.001) from our previously published figures for normal specimens of these glands.", "contents": "A qualitative and quantitative electronmicroscopic study of the structure of the adenoid cystic carcinoma of human minor salivary glands. The fine structural characteristics of five adenoid cystic carcinomas of human minor salivary galnds and a quantitative assessment of the relative volumes occupied by morphologically defined cell types in these tumors are reported. We observed that the cyst-like spaces which give the characteristic cribriform pattern to the adenoid cystic carcinoma contain replicated basement membrane-like materail. Material comprisimg aggregates of fine tubules having a median diameter of 270 A, and rounded, electron dense bodies were noted within duct-like lumena of one tumor. In addition, dilatation of the intercellular spaces and squamous metaplasia were noted. From 500 electronmicrographs obtained by standardized techniques and used for the morphological part of the study, 175 were selected by a random sampling method and analyzed by the stereological technique of point counting. This method demonstrated that duct type cells occupied 75% by volume of the tumor in these glands; myoepithelial cells occupied 3%, acinar cells occupied 2%, and other tissues occupied 22% of the tumors. These proportions differ significantly (P less than 0.001) from our previously published figures for normal specimens of these glands."} {"id": "PMID:171356", "title": "Evaluation of parotid gland masses by rectilinear scanning.", "content": "Twelve salivary gland scans, done preoperatively for evaluation of parotid masses, included nine cases of Warthin's tumor. In addition to Warthin's tumor showing an accumulation of pertechnetate, increased activity was also present in two cases of mixed tumors. Warthin's tumor may also show decreased activity, with or without a large cystic component. Therefore, the interpretation of preoperative salivary gland scans must be made with caution.", "contents": "Evaluation of parotid gland masses by rectilinear scanning. Twelve salivary gland scans, done preoperatively for evaluation of parotid masses, included nine cases of Warthin's tumor. In addition to Warthin's tumor showing an accumulation of pertechnetate, increased activity was also present in two cases of mixed tumors. Warthin's tumor may also show decreased activity, with or without a large cystic component. Therefore, the interpretation of preoperative salivary gland scans must be made with caution."} {"id": "PMID:171357", "title": "Melanotic neuroectodermal tumor of infancy.", "content": "Recurrence of a melanotic neuroectodermal tumor of infancy was clinically evident eight weeks after the original lesion had been surgically removed. Concentrations of urinary vanilmandelic acid were elevated immediately after surgery but returned to normal a month after removal of the tumor. The location of the recurrent tumor, the rapidity of recurrence, and the concentrations of urinary VMA favor a theory of neural crest origin.", "contents": "Melanotic neuroectodermal tumor of infancy. Recurrence of a melanotic neuroectodermal tumor of infancy was clinically evident eight weeks after the original lesion had been surgically removed. Concentrations of urinary vanilmandelic acid were elevated immediately after surgery but returned to normal a month after removal of the tumor. The location of the recurrent tumor, the rapidity of recurrence, and the concentrations of urinary VMA favor a theory of neural crest origin."} {"id": "PMID:171361", "title": "Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy.", "content": "The sexual precocity of polyostotic fibrous dysplasia is occasionally accompanied by other endocrine disorders, but in only two previous instances has Cushing syndrome been reported. The history of a 6-month-old girl is presented, in whom this syndrome was complicated by congenital Cushings syndrome. Although endocrinopathies of polyostotic fibrous dysplasia have usually been ascribed to a central (hypothalamic) origin, the findings in this patient suggest autonomous hyperfunction of the peripheral endocrine glands, with the Cushing syndrome caused by hyperplastic nodules in the adrenal glands and the precocity by luteinized follicular cysts of the ovary.", "contents": "Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy. The sexual precocity of polyostotic fibrous dysplasia is occasionally accompanied by other endocrine disorders, but in only two previous instances has Cushing syndrome been reported. The history of a 6-month-old girl is presented, in whom this syndrome was complicated by congenital Cushings syndrome. Although endocrinopathies of polyostotic fibrous dysplasia have usually been ascribed to a central (hypothalamic) origin, the findings in this patient suggest autonomous hyperfunction of the peripheral endocrine glands, with the Cushing syndrome caused by hyperplastic nodules in the adrenal glands and the precocity by luteinized follicular cysts of the ovary."} {"id": "PMID:171363", "title": "Viral hepatitis: recent developments and prospects for prevention.", "content": "During the past decade new development in hepatitis research have shed new light on the etiologic, epidemiologic, immunologic, and prophylactic aspects of type A and B hepatitis virus infection. Recent advances in hepatitis A virus research include: (1) identification of the virus as a 27 nm particle with characteristics resembling an enterovirus, (2) transmission of the infection to marmosets and chimpanzees, and (3) development of specific complement fixation and immune adherence antibody tests. Recent advances in hepatitis B research include: (1) identification of the virus as a 42 nm particle (Dane particle) containing an outer coat, the hepatitis B surface antigen, and an inner core, the hepatitis B core antigen, (2) development of specific tests to detect the hepatitis B antigens and their respective antibodies, (3) transmission of the infection to chimpanzees, (4) development of a specific hepatitis B immune serum globulin, and (5) development of an inactivated hepatitis B vaccine.", "contents": "Viral hepatitis: recent developments and prospects for prevention. During the past decade new development in hepatitis research have shed new light on the etiologic, epidemiologic, immunologic, and prophylactic aspects of type A and B hepatitis virus infection. Recent advances in hepatitis A virus research include: (1) identification of the virus as a 27 nm particle with characteristics resembling an enterovirus, (2) transmission of the infection to marmosets and chimpanzees, and (3) development of specific complement fixation and immune adherence antibody tests. Recent advances in hepatitis B research include: (1) identification of the virus as a 42 nm particle (Dane particle) containing an outer coat, the hepatitis B surface antigen, and an inner core, the hepatitis B core antigen, (2) development of specific tests to detect the hepatitis B antigens and their respective antibodies, (3) transmission of the infection to chimpanzees, (4) development of a specific hepatitis B immune serum globulin, and (5) development of an inactivated hepatitis B vaccine."} {"id": "PMID:171364", "title": "The effects of stibophen on phosphofructokinases and aldolases of adult filariids.", "content": "Trivalent organic antimonials, such as stibophen, have been employed for the chemotherapy of schistosome and filariid infections. The effects of stibophen on adult Litomosoides carinii, Dipetalonema witei (= viteae), and Brugia pahangi were examined. In vitro, lactate accumulation was markedly inhibited by the antimonials as was phosphofructokinase activities in homogenates. Incubation of filariids with stibophen and determination of internal concentrations of hexose phosphate also indicated a decreased phosphofructokinase activity. In addition, a second inhibitory effect of stibophen on aldolase has been observed which appears to be specific for stibophen and is not displayed by potassium antimony tartrate. Both inhibitory activities may contribute to the chemotherapeutic effect of stibophen. In addition to the schistosomes and filariids, stibophen also inhibits Ascaris and Hymenolepis diminuta phosphofructokinases at low concentrations, where no inhibition of the corresponding mammalian liver enzyme was demonstrable.", "contents": "The effects of stibophen on phosphofructokinases and aldolases of adult filariids. Trivalent organic antimonials, such as stibophen, have been employed for the chemotherapy of schistosome and filariid infections. The effects of stibophen on adult Litomosoides carinii, Dipetalonema witei (= viteae), and Brugia pahangi were examined. In vitro, lactate accumulation was markedly inhibited by the antimonials as was phosphofructokinase activities in homogenates. Incubation of filariids with stibophen and determination of internal concentrations of hexose phosphate also indicated a decreased phosphofructokinase activity. In addition, a second inhibitory effect of stibophen on aldolase has been observed which appears to be specific for stibophen and is not displayed by potassium antimony tartrate. Both inhibitory activities may contribute to the chemotherapeutic effect of stibophen. In addition to the schistosomes and filariids, stibophen also inhibits Ascaris and Hymenolepis diminuta phosphofructokinases at low concentrations, where no inhibition of the corresponding mammalian liver enzyme was demonstrable."} {"id": "PMID:171365", "title": "Heligmosomoides polygyrus (=Nematospiroides dubius): the development of self-cure and/or protection in several strains of mice.", "content": "Strains of outbred (ICR/CD1 and S--W) and inbred (BALB/C and C57BL/6) mice vaccinated subcutaneously (SQ) with 500, 1,000, or 2,000 exsheathed Heligmosomoides polygyrus larvae developed varying levels of protection upon subsequent oral challenge with larvae. In contrast, the inbred C3H/HEJ strain failed to develop protection at any dosage level tested. ICR/CD1 mice vaccinated intraperitoneally with exsheathed larvae developed a high level of resistance but exhibited extensive adhesions of the viscera. When ensheathed larvae were used for vaccination, ICR/CD1 mice developed a moderate level of protection; but 1% of the vaccine dose was recovered in the intestine as adult stages. Both the inbred and outbred strains given multiple oral infections developed a protection response similar to that strain's response following parenteral vaccination. The specificity of this protection was demonstrated using various complex foreign antigens. In contrast, the self-cure response was observed only in the S--W strain.", "contents": "Heligmosomoides polygyrus (=Nematospiroides dubius): the development of self-cure and/or protection in several strains of mice. Strains of outbred (ICR/CD1 and S--W) and inbred (BALB/C and C57BL/6) mice vaccinated subcutaneously (SQ) with 500, 1,000, or 2,000 exsheathed Heligmosomoides polygyrus larvae developed varying levels of protection upon subsequent oral challenge with larvae. In contrast, the inbred C3H/HEJ strain failed to develop protection at any dosage level tested. ICR/CD1 mice vaccinated intraperitoneally with exsheathed larvae developed a high level of resistance but exhibited extensive adhesions of the viscera. When ensheathed larvae were used for vaccination, ICR/CD1 mice developed a moderate level of protection; but 1% of the vaccine dose was recovered in the intestine as adult stages. Both the inbred and outbred strains given multiple oral infections developed a protection response similar to that strain's response following parenteral vaccination. The specificity of this protection was demonstrated using various complex foreign antigens. In contrast, the self-cure response was observed only in the S--W strain."} {"id": "PMID:171366", "title": "Bench surgery and renal autotransplantation in the pediatric patient.", "content": "A new operative procedure in renal surgery has evolved from the extensive recent experience in kidney transplantation. Bench surgery and autotransplantation have not been, as yet, fully exploited by surgeons caring for children. This approach to reconstruction of renal substance and renal vessels has as its greatest dividend conservation of kidney tissue. The operation has specific applicability for selected cases of: (1) renovascular hypertension; (2) congenital obstructive uropathy; (3) bilateral Wilms' tumor, and; (4) renal trauma in children.", "contents": "Bench surgery and renal autotransplantation in the pediatric patient. A new operative procedure in renal surgery has evolved from the extensive recent experience in kidney transplantation. Bench surgery and autotransplantation have not been, as yet, fully exploited by surgeons caring for children. This approach to reconstruction of renal substance and renal vessels has as its greatest dividend conservation of kidney tissue. The operation has specific applicability for selected cases of: (1) renovascular hypertension; (2) congenital obstructive uropathy; (3) bilateral Wilms' tumor, and; (4) renal trauma in children."} {"id": "PMID:171367", "title": "Preoperative therapy for unresectable malignant tumors in children.", "content": "Thirty-six children with initially unresectable malignant tumors were managed with pre- and postoperative therapy combined with reduction of primary tumor burden by total or subtotal resection. The proportion of patients achieving long-term tumor-free survival after surgery was 0.48 in the Wilms' tumor group and 0.60 among patients with other regionally unresectable malignant neoplasms. These results are encouraging in an otherwise high mortality situation.", "contents": "Preoperative therapy for unresectable malignant tumors in children. Thirty-six children with initially unresectable malignant tumors were managed with pre- and postoperative therapy combined with reduction of primary tumor burden by total or subtotal resection. The proportion of patients achieving long-term tumor-free survival after surgery was 0.48 in the Wilms' tumor group and 0.60 among patients with other regionally unresectable malignant neoplasms. These results are encouraging in an otherwise high mortality situation."} {"id": "PMID:171369", "title": "Differences in cAMP levels in the gingival fluid of diabetics and nondiabetics.", "content": "Gingival fluid from eight control subjects and ten diabetics was collected and the content of cAMP and protein in the fluid was assayed to determine the nature of the biochemical changes occurring in the gingival fluid due to diabetes. The gingival fluid of the control subjects had a cAMP concentration of 2.4 X 10(-6) M, which was a hundredfold greater than that seen in serum, thus suggesting that the cAMP in the fluid resulted from active synthesis by the gingival cells and was not merely a transudate from the blood. The gingival fluid of the diabetics contained only one-seventh the level of cAMP seen in the control group. It is suggested that the decreased level of cAMP seen in the givgival fluid of diabetics may be a manifestation of a defect in the cAMP forming mechanism of the gingival tissue, which may reflect the systemic etiology of diabetes. It was also found that in the control subjects the content of cAMP in the gingival fluid was in inverse proportion to the volume of exudate in the gingival crevice. No such relationship was seen in the diabetic group. It appears that the level of cAMP present in the gingival fluid of normal individuals without any generalized endocrine deficiencies may be used as an additional indicator of the inflammatory status of the gingival tissues, along with the clinical evaluation based on gingival index.", "contents": "Differences in cAMP levels in the gingival fluid of diabetics and nondiabetics. Gingival fluid from eight control subjects and ten diabetics was collected and the content of cAMP and protein in the fluid was assayed to determine the nature of the biochemical changes occurring in the gingival fluid due to diabetes. The gingival fluid of the control subjects had a cAMP concentration of 2.4 X 10(-6) M, which was a hundredfold greater than that seen in serum, thus suggesting that the cAMP in the fluid resulted from active synthesis by the gingival cells and was not merely a transudate from the blood. The gingival fluid of the diabetics contained only one-seventh the level of cAMP seen in the control group. It is suggested that the decreased level of cAMP seen in the givgival fluid of diabetics may be a manifestation of a defect in the cAMP forming mechanism of the gingival tissue, which may reflect the systemic etiology of diabetes. It was also found that in the control subjects the content of cAMP in the gingival fluid was in inverse proportion to the volume of exudate in the gingival crevice. No such relationship was seen in the diabetic group. It appears that the level of cAMP present in the gingival fluid of normal individuals without any generalized endocrine deficiencies may be used as an additional indicator of the inflammatory status of the gingival tissues, along with the clinical evaluation based on gingival index."} {"id": "PMID:171373", "title": "Metabolism of 8-(methylthio)cyclic 3',5'-adenosine monophosphate by rats and dogs after oral or intravenous dosing and in vitro by subcellular preparations of dog liver.", "content": "8-(Methylthio-14C or -35S)cyclic 3',5'-adenosine monophosphate (I) was given intravenously to rats (5 mg/kg) and orally and intravenously to dogs (0.25, 2.5, or 50 mg/kg). Oral doses were absorbed well but slowly. Plasma half-lives in dogs were about 3 hr after oral or intravenous doses of 0.25 or 2.5 mg/kg and ranged from 5 to 12 hr after oral or intravenous doseas of 50 mg/kg. Plasma glucose and insulin concentrations in dogs were increased by oral or intravenous doses of the compound. Regardless of the route, excretion of radioactivity by rats and dogs at all doses was chiefly in the urine (74-87% of the dose); the remainder was excreted in the feces or bile. Compound I was rapidly distributed to most tissues of dogs but entered the brain and certain portions of the eye slowly and to a limited extent. Urine and plasma of dogs and urine of rats contained I, 8-(methylthio)adenosine, and at least two other unidentified metabolites. Compound I and cyclic 3',5'-adenosine monophosphate were metabolized in vitro by the soluble fraction of dog liver to form 8-(methylthio)adenosine-5'-monophosphate and adenosine-5'-monophosphate, respectively. These compounds were further converted to 8-(methylthio)adenosine and adenosine, respectively. Compound I was metabolized in vitro more slowly than cyclic 3',5'-adenosine monophosphate.", "contents": "Metabolism of 8-(methylthio)cyclic 3',5'-adenosine monophosphate by rats and dogs after oral or intravenous dosing and in vitro by subcellular preparations of dog liver. 8-(Methylthio-14C or -35S)cyclic 3',5'-adenosine monophosphate (I) was given intravenously to rats (5 mg/kg) and orally and intravenously to dogs (0.25, 2.5, or 50 mg/kg). Oral doses were absorbed well but slowly. Plasma half-lives in dogs were about 3 hr after oral or intravenous doses of 0.25 or 2.5 mg/kg and ranged from 5 to 12 hr after oral or intravenous doseas of 50 mg/kg. Plasma glucose and insulin concentrations in dogs were increased by oral or intravenous doses of the compound. Regardless of the route, excretion of radioactivity by rats and dogs at all doses was chiefly in the urine (74-87% of the dose); the remainder was excreted in the feces or bile. Compound I was rapidly distributed to most tissues of dogs but entered the brain and certain portions of the eye slowly and to a limited extent. Urine and plasma of dogs and urine of rats contained I, 8-(methylthio)adenosine, and at least two other unidentified metabolites. Compound I and cyclic 3',5'-adenosine monophosphate were metabolized in vitro by the soluble fraction of dog liver to form 8-(methylthio)adenosine-5'-monophosphate and adenosine-5'-monophosphate, respectively. These compounds were further converted to 8-(methylthio)adenosine and adenosine, respectively. Compound I was metabolized in vitro more slowly than cyclic 3',5'-adenosine monophosphate."} {"id": "PMID:171374", "title": "Effects of selected drugs on an auditory or thalamic conditioned stimulus eliciting recruitment in the cat.", "content": "Minimally effective oral doses of chlorpromazine, imipramine, and pentobarbital necessary to block a discrete trial (bar-press) conditioned avoidance response were compared in cats chronically implanted with electrodes over the cerebral cortex and in the nucleus centralis medialis of the thalamus. Three conditioned stimulus contingencies consisting of tone and low or high voltage thalamic stimulation were presented. Minimal conditioned response blocking doses of these agents produced only slight qualitative changes in cortically recorded recruitment. Drug treatment affected the conditioned stimulus contingencies differentially, and the rank order in terms of ease of disruption of the conditioned avoidance response was high voltage thalamic conditioned stimulus greater than low voltage thalamic conditioned stimulus greater than auditory conditioned stimulus. The differential effect of these drugs might have been due to the additive inhibition of these agents and the thalamic conditioned stimulus on performance. With the exception of chlorpromazine, the behavioral effects of these drugs and their effects on recruitment were dissociated.", "contents": "Effects of selected drugs on an auditory or thalamic conditioned stimulus eliciting recruitment in the cat. Minimally effective oral doses of chlorpromazine, imipramine, and pentobarbital necessary to block a discrete trial (bar-press) conditioned avoidance response were compared in cats chronically implanted with electrodes over the cerebral cortex and in the nucleus centralis medialis of the thalamus. Three conditioned stimulus contingencies consisting of tone and low or high voltage thalamic stimulation were presented. Minimal conditioned response blocking doses of these agents produced only slight qualitative changes in cortically recorded recruitment. Drug treatment affected the conditioned stimulus contingencies differentially, and the rank order in terms of ease of disruption of the conditioned avoidance response was high voltage thalamic conditioned stimulus greater than low voltage thalamic conditioned stimulus greater than auditory conditioned stimulus. The differential effect of these drugs might have been due to the additive inhibition of these agents and the thalamic conditioned stimulus on performance. With the exception of chlorpromazine, the behavioral effects of these drugs and their effects on recruitment were dissociated."} {"id": "PMID:171375", "title": "Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration.", "content": "Administration of cadmium chloride (1.0 mg/kg s.c.) to rats, twice a day for 7 days, significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase, markedly increased the concentration of hepatic cyclic adenosine monophosphate and circulating blood glucose and significantly reduced serum insulin levels. Furthermore, subacute exposure to cadmium induced glucose intolerance that was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices and marked inhibition of phentolamine-stimulated insulin release. In contrast to cadmium, administration of selenium dioxide (2 X 1.0 mg/kg/day s.c., 7 days) failed to alter significantly the activities of gluconeogenic enzymes, hepatic cyclic adenosine monophosphate, blood glucose or serum insulin levels, glucose tolerance or the pancreatic secretory activity. However, administration of selenium concurrently with cadmium completely prevented the cadmium-induced increases of hepatic gluconeogenic enzymes. Treatment with selenium ameliorated the cadmium-induced hyperglycemia, hypoinsulinemia, glucose intolerance and the suppression of pancreatic secretory activity, whereas it failed to alter significantly the cadmium-induced elevation of hepatic cyclic AMP levels. Data provide evidence suggesting that subacute exposure to cadmium alters several parameters of carbohydrate metabolism and suppresses pancreatic secretory activity and that administration of selenium alone is without any appreciable effect on the above parameters. However, administration of selenium concurrently with cadmium prevents, to varying degrees, several of the cadmium-induced metabolic and functional changes.", "contents": "Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration. Administration of cadmium chloride (1.0 mg/kg s.c.) to rats, twice a day for 7 days, significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase, markedly increased the concentration of hepatic cyclic adenosine monophosphate and circulating blood glucose and significantly reduced serum insulin levels. Furthermore, subacute exposure to cadmium induced glucose intolerance that was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices and marked inhibition of phentolamine-stimulated insulin release. In contrast to cadmium, administration of selenium dioxide (2 X 1.0 mg/kg/day s.c., 7 days) failed to alter significantly the activities of gluconeogenic enzymes, hepatic cyclic adenosine monophosphate, blood glucose or serum insulin levels, glucose tolerance or the pancreatic secretory activity. However, administration of selenium concurrently with cadmium completely prevented the cadmium-induced increases of hepatic gluconeogenic enzymes. Treatment with selenium ameliorated the cadmium-induced hyperglycemia, hypoinsulinemia, glucose intolerance and the suppression of pancreatic secretory activity, whereas it failed to alter significantly the cadmium-induced elevation of hepatic cyclic AMP levels. Data provide evidence suggesting that subacute exposure to cadmium alters several parameters of carbohydrate metabolism and suppresses pancreatic secretory activity and that administration of selenium alone is without any appreciable effect on the above parameters. However, administration of selenium concurrently with cadmium prevents, to varying degrees, several of the cadmium-induced metabolic and functional changes."} {"id": "PMID:171376", "title": "Effects of pressure and anesthetics on conduction and synaptic transmission.", "content": "The antagonism observed between pressure and anesthesia in intact animals suggests that pressure antagonism may be a promising criterion for identifying the effects of anesthetics which are important to loss of responsiveness. It is therefore of interest to compare the effects of pressure and anesthesia on conduction and on synaptic transmission, which have often been proposed as possible alternative cellular sites of anesthesia. The model used in this study is the isolated rat superior cervical ganglion. Helium pressure (35-103 atm) antagonized partial conduction block of the preganglionic nerve by halothane(0.5 and 1 mM). Helium pressure failed to antagonize the depressant effects of halothane (0.25-0.5 mM) on nicotinic transmission and of halothane or methoxyflurane (0.24 mM) on muscarinic transmission in the ganglion. Pressure itself severely depressed synaptic transmission and added to the depressant effects of the anesthetics. Conduction block as a possible cellular mechanism of anesthesia therefore meets the proposed criterion of pressure reversibility. In contrast, pressure does not antagonize anesthetic depression of excitatory synaptic transmission in the rat superior cervical ganglion.", "contents": "Effects of pressure and anesthetics on conduction and synaptic transmission. The antagonism observed between pressure and anesthesia in intact animals suggests that pressure antagonism may be a promising criterion for identifying the effects of anesthetics which are important to loss of responsiveness. It is therefore of interest to compare the effects of pressure and anesthesia on conduction and on synaptic transmission, which have often been proposed as possible alternative cellular sites of anesthesia. The model used in this study is the isolated rat superior cervical ganglion. Helium pressure (35-103 atm) antagonized partial conduction block of the preganglionic nerve by halothane(0.5 and 1 mM). Helium pressure failed to antagonize the depressant effects of halothane (0.25-0.5 mM) on nicotinic transmission and of halothane or methoxyflurane (0.24 mM) on muscarinic transmission in the ganglion. Pressure itself severely depressed synaptic transmission and added to the depressant effects of the anesthetics. Conduction block as a possible cellular mechanism of anesthesia therefore meets the proposed criterion of pressure reversibility. In contrast, pressure does not antagonize anesthetic depression of excitatory synaptic transmission in the rat superior cervical ganglion."} {"id": "PMID:171378", "title": "Synaptic transfer at a vertebrate central nervous system synapse.", "content": "1. The relation between presynaptic depolarization and transmitter release was examined at a synapse between a M\u00fcller axon and a lateral interneurone in the spinal cord of the lamprey. Two micro-electrodes, one for passing current and the other for recording the resulting voltage change, were placed in the presynaptic axon; a single electrode for recording the post-synaptic potential produced by release of transmitter was placed in the post-synaptic cell. 2. When action potentials were blocked with tetrodotoxin, brief depolarizing pulses in the presynaptic fibre were as effective as the action potential had been in producing transmitter release. 3. The release process had an apparent threshold depolarization of 40-50 mV and saturated at presynaptic depolarizations of the order of 100 mV. Increasing the duration of the presynaptic pulse increased the maximum level of release. 4. Displacing the presynaptic voltage recording electrode from the position of synaptic contact toward the current passing electrode increased the apparent depolarization required to produce a given level of transmitter release. This shift in the input-output relation was consistent in magnitude with the voltage attenuation between the presynaptic recording electrode and the synapse expected from the space constant of the fibre. 5. The effect of conditioning hyperpolarization and depolarization of the presynaptic fibre on subsequent transmitter release by brief depolarizing pulses was examined. No effect was observed when the presynaptic recording electrode was in the region of synaptic contact. When the presynaptic electrode was not so positioned, conditioning effects were observed which depended on electode position and could be attributed to changes in the space constant of the presynaptic fibre. No conditioning effects were observed on transmitter release by the action potential.", "contents": "Synaptic transfer at a vertebrate central nervous system synapse. 1. The relation between presynaptic depolarization and transmitter release was examined at a synapse between a M\u00fcller axon and a lateral interneurone in the spinal cord of the lamprey. Two micro-electrodes, one for passing current and the other for recording the resulting voltage change, were placed in the presynaptic axon; a single electrode for recording the post-synaptic potential produced by release of transmitter was placed in the post-synaptic cell. 2. When action potentials were blocked with tetrodotoxin, brief depolarizing pulses in the presynaptic fibre were as effective as the action potential had been in producing transmitter release. 3. The release process had an apparent threshold depolarization of 40-50 mV and saturated at presynaptic depolarizations of the order of 100 mV. Increasing the duration of the presynaptic pulse increased the maximum level of release. 4. Displacing the presynaptic voltage recording electrode from the position of synaptic contact toward the current passing electrode increased the apparent depolarization required to produce a given level of transmitter release. This shift in the input-output relation was consistent in magnitude with the voltage attenuation between the presynaptic recording electrode and the synapse expected from the space constant of the fibre. 5. The effect of conditioning hyperpolarization and depolarization of the presynaptic fibre on subsequent transmitter release by brief depolarizing pulses was examined. No effect was observed when the presynaptic recording electrode was in the region of synaptic contact. When the presynaptic electrode was not so positioned, conditioning effects were observed which depended on electode position and could be attributed to changes in the space constant of the presynaptic fibre. No conditioning effects were observed on transmitter release by the action potential."} {"id": "PMID:171379", "title": "Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse.", "content": "1. Post-synaptic responses to acetylcholine (ACh) released from nerve terminals and from iontophoretic micropipettes were investigated in skeletal muscle fibres of the snake. Each fibre has a compact end-plate consisting of fifty to seventy synaptic boutons. The fibres were voltage clamped, and synaptic currents were recorded from visually identified end-plates. 2. When acetylcholinesterase (AChE) is inhibited, a potentiating interaction is observed between two or more quanta that are released close to each other from a synaptic bouton and act upon partially overlapping postsynaptic areas. The potentiation is expressed as a prolongation of the synaptic current. This potentiation also occurs under normal conditions of release when about 300 quanta are distributed over the entire end-plate, so thet the presynaptic release sites are separated by an average of 2 mum. An analogous potentiating interaction is observed when micropipettes, closely apposed to the subsynaptic membrane, substitute for quantal release sites. ACh from one pipette potentiates the response to ACh from another pipette less than 2 mum away. 3. In contrast, with AChE fully active no post-synaptic potentiation is seen when the normal complement of quanta is released over the entire end-plate. The time course of the synaptic currents in response to a single quantum or to 300 quanta is similar. It is concluded that functionally the quanta act independently of each other, because AChE isolates each quantum from its neighbours by limiting the lifetime of ACh and its lateral diffusion in the synaptic cleft. The estimated area over which a quantum normally acts is less than 2mum2. 4. Post-synaptic receptors are not saturated by the ACh in a quantum, since the peak of the quantal response adds linearly to the response produced by an appropriate background concentration of ACh from a pipette. This conclusion is supported by the observation that upon inhibition of AChE the peak amplitude of the quantal current response increases by about 20% with no change in its time to peak. 5. It is suggested that post-synaptic potentiation between quanta may play a role in signalling at synapses in which non-linear dose-response characteristics have been observed and where transmitter is not as repidly inactivated as the neuromuscular synapse.", "contents": "Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. 1. Post-synaptic responses to acetylcholine (ACh) released from nerve terminals and from iontophoretic micropipettes were investigated in skeletal muscle fibres of the snake. Each fibre has a compact end-plate consisting of fifty to seventy synaptic boutons. The fibres were voltage clamped, and synaptic currents were recorded from visually identified end-plates. 2. When acetylcholinesterase (AChE) is inhibited, a potentiating interaction is observed between two or more quanta that are released close to each other from a synaptic bouton and act upon partially overlapping postsynaptic areas. The potentiation is expressed as a prolongation of the synaptic current. This potentiation also occurs under normal conditions of release when about 300 quanta are distributed over the entire end-plate, so thet the presynaptic release sites are separated by an average of 2 mum. An analogous potentiating interaction is observed when micropipettes, closely apposed to the subsynaptic membrane, substitute for quantal release sites. ACh from one pipette potentiates the response to ACh from another pipette less than 2 mum away. 3. In contrast, with AChE fully active no post-synaptic potentiation is seen when the normal complement of quanta is released over the entire end-plate. The time course of the synaptic currents in response to a single quantum or to 300 quanta is similar. It is concluded that functionally the quanta act independently of each other, because AChE isolates each quantum from its neighbours by limiting the lifetime of ACh and its lateral diffusion in the synaptic cleft. The estimated area over which a quantum normally acts is less than 2mum2. 4. Post-synaptic receptors are not saturated by the ACh in a quantum, since the peak of the quantal response adds linearly to the response produced by an appropriate background concentration of ACh from a pipette. This conclusion is supported by the observation that upon inhibition of AChE the peak amplitude of the quantal current response increases by about 20% with no change in its time to peak. 5. It is suggested that post-synaptic potentiation between quanta may play a role in signalling at synapses in which non-linear dose-response characteristics have been observed and where transmitter is not as repidly inactivated as the neuromuscular synapse."} {"id": "PMID:171380", "title": "The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse.", "content": "1. The sensitivity of the subsynaptic membrane of twitch muscles of the frog and snake to iontophoretically applied acetylcholine (ACh) was determined. Optimal placement of ACh micropipettes on to the postsynaptic membrane resulted in potentials that were similar, though not identical, to the miniature excitatory post-synaptic potentials (min e.p.s.p.s). A sensitive bio-assay was developed to measure the output of ACh from micropipettes; this allowed an estimate to be made of the upper limit of the number of ACh molecules in a quantum of transmitter that is released from the nerve to produce a min e.p.s.p. 2. The assay to calibrate the output of ACh from micropipettes used the end-plate of the snake muscle as an ACh concentration detector. The end-plate was situated within a few mum of an oil-water interface, and a 0-6 nl. droplet of Ringer solution containing a known concentration of ACh (1 muM or less) was formed in the oil phase. The droplet was brought to the interface and, upon touching it, discharged its contents into the Ringer phase immediately above the end-plate. This resulted in a membrane depolarization that was recorded with an intracellular microelectrode. By applying droplets containing various known ACh concentrations a standard curve was constructed. To measure the ACh output of micropipettes a 0-6 nl. droplet of Ringer solution was suspended in the oil. The ACh pipette tip was inserted into the droplet and several thousand pulses of ACh were then delivered. The ACh content of the test droplet was measured by comparing its effectiveness in depolarizing the end-plate with the standard curve. In this manner the number of ACh molecules released in a single pulse was determined as a function of charge passed through the pipette. The output of ACh was linear and an average of 30,000 molecules of ACh were released per pC. 3. The sensitivity of the subsynaptic membrane to iontophoretically applied ACh, using the linear slopes of dose-response curves, in preparations from frog and snake treated with anticholinesterases was usually about 5 mV/pC. It follows that 6000 molecules of ACh are sufficient to produce a depolarization of 1 mV in the subsynaptic membrane. 4. The mean min e.p.s.p.s of muscle fibres treated with anticholinesterase range from 1 to 3 mV. Since the ACh released from an iontophoretic pipette is less effective than the same amount released from the nerve, it is concluded that a quantum of transmitter consists of less than 10,000 molecules of ACh. 5. It is calculated that for each molecule of ACh released in a quantum there results a minimum net flow of 3000 univalent ions across the synaptic membrane.", "contents": "The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. 1. The sensitivity of the subsynaptic membrane of twitch muscles of the frog and snake to iontophoretically applied acetylcholine (ACh) was determined. Optimal placement of ACh micropipettes on to the postsynaptic membrane resulted in potentials that were similar, though not identical, to the miniature excitatory post-synaptic potentials (min e.p.s.p.s). A sensitive bio-assay was developed to measure the output of ACh from micropipettes; this allowed an estimate to be made of the upper limit of the number of ACh molecules in a quantum of transmitter that is released from the nerve to produce a min e.p.s.p. 2. The assay to calibrate the output of ACh from micropipettes used the end-plate of the snake muscle as an ACh concentration detector. The end-plate was situated within a few mum of an oil-water interface, and a 0-6 nl. droplet of Ringer solution containing a known concentration of ACh (1 muM or less) was formed in the oil phase. The droplet was brought to the interface and, upon touching it, discharged its contents into the Ringer phase immediately above the end-plate. This resulted in a membrane depolarization that was recorded with an intracellular microelectrode. By applying droplets containing various known ACh concentrations a standard curve was constructed. To measure the ACh output of micropipettes a 0-6 nl. droplet of Ringer solution was suspended in the oil. The ACh pipette tip was inserted into the droplet and several thousand pulses of ACh were then delivered. The ACh content of the test droplet was measured by comparing its effectiveness in depolarizing the end-plate with the standard curve. In this manner the number of ACh molecules released in a single pulse was determined as a function of charge passed through the pipette. The output of ACh was linear and an average of 30,000 molecules of ACh were released per pC. 3. The sensitivity of the subsynaptic membrane to iontophoretically applied ACh, using the linear slopes of dose-response curves, in preparations from frog and snake treated with anticholinesterases was usually about 5 mV/pC. It follows that 6000 molecules of ACh are sufficient to produce a depolarization of 1 mV in the subsynaptic membrane. 4. The mean min e.p.s.p.s of muscle fibres treated with anticholinesterase range from 1 to 3 mV. Since the ACh released from an iontophoretic pipette is less effective than the same amount released from the nerve, it is concluded that a quantum of transmitter consists of less than 10,000 molecules of ACh. 5. It is calculated that for each molecule of ACh released in a quantum there results a minimum net flow of 3000 univalent ions across the synaptic membrane."} {"id": "PMID:171381", "title": "Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen.", "content": "1. The effects of prostaglandins E2 (PGE2) and indomethacin on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen, at different calcium concentrations in the perfusion medium: 0-26, 0-65 and 2-6 mve stimulation and in the overflow of the transmitter. PGE2 was more effective in reducing transmitter overflow at 5 than at 30 Hz. 3. Indomethacin, 14-0 muM, prevented the release of PGE-like material in the venous effluent of the spleen elicited by either nerve stimulation or by exogenous noradrenaline. 4. During exposure to 14-0 muM indomethacin there was no increase in responses to nerve stimulation or in the overflow of noradrenaline elicited by nerve stimulation at 5 or at 30 Hz. 5. Similar results to those obtained with exogenous PGE2 and with indomethacin in the presence of 2-6 mM calcium, were observed when the experiments were carried out in the presence of either 0-65 or 0-26 mM calcium. 6. In the presence of the alpha-adrenoceptor blocking agents, phenoxybenzamine (2-9 muM) or phentolamine (3-1 muM), the increase in transmitter overflow obtained during stimulation was 6-5 and 8-3-fold respectively. 7. Since inhibition of the synthesis of PGE did not increase transmitter overflow during nerve stimulation, it appears that the proposed negative feed-back mechanism mediated by endogenous prostaglandins does not play an important physiological role in the regulation of adrenergic neurotransmission in the cat spleen. In this tissue the major endogenous negative feed-back regulatory mechanism is triggered by the neurotransmitter through the activation of prejunctional alpha-adrenoceptors.", "contents": "Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen. 1. The effects of prostaglandins E2 (PGE2) and indomethacin on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen, at different calcium concentrations in the perfusion medium: 0-26, 0-65 and 2-6 mve stimulation and in the overflow of the transmitter. PGE2 was more effective in reducing transmitter overflow at 5 than at 30 Hz. 3. Indomethacin, 14-0 muM, prevented the release of PGE-like material in the venous effluent of the spleen elicited by either nerve stimulation or by exogenous noradrenaline. 4. During exposure to 14-0 muM indomethacin there was no increase in responses to nerve stimulation or in the overflow of noradrenaline elicited by nerve stimulation at 5 or at 30 Hz. 5. Similar results to those obtained with exogenous PGE2 and with indomethacin in the presence of 2-6 mM calcium, were observed when the experiments were carried out in the presence of either 0-65 or 0-26 mM calcium. 6. In the presence of the alpha-adrenoceptor blocking agents, phenoxybenzamine (2-9 muM) or phentolamine (3-1 muM), the increase in transmitter overflow obtained during stimulation was 6-5 and 8-3-fold respectively. 7. Since inhibition of the synthesis of PGE did not increase transmitter overflow during nerve stimulation, it appears that the proposed negative feed-back mechanism mediated by endogenous prostaglandins does not play an important physiological role in the regulation of adrenergic neurotransmission in the cat spleen. In this tissue the major endogenous negative feed-back regulatory mechanism is triggered by the neurotransmitter through the activation of prejunctional alpha-adrenoceptors."} {"id": "PMID:171385", "title": "Disturbed wards--do we need them?", "content": "This is a study of forty-three female residents of a continued care state psychiatric facility who were transferred from a ward for highly disturbed persons to a ward based on a geographical unit system. One year after the transfer thirty-eight patients were improved, particularly in the area of behavior symptomatology. A change in perceived expectations of both patients and staff seemed to be primarily responsible for the positive change noted.", "contents": "Disturbed wards--do we need them? This is a study of forty-three female residents of a continued care state psychiatric facility who were transferred from a ward for highly disturbed persons to a ward based on a geographical unit system. One year after the transfer thirty-eight patients were improved, particularly in the area of behavior symptomatology. A change in perceived expectations of both patients and staff seemed to be primarily responsible for the positive change noted."} {"id": "PMID:171386", "title": "The psychiatric nurse as outpatient psychotherapist.", "content": "Nursing therapy has predominantly reflected treatment within inpatient settings. There is little focus on outpatient services, where the psychiatric nurse can function as psychotherapist. Specific roles of one outpatient nurse therapist are outlined. Concrete guidelines in terms of supervision, support, and self-exploration are delineated for implementation by the nurse as outpatient psychotherapist.", "contents": "The psychiatric nurse as outpatient psychotherapist. Nursing therapy has predominantly reflected treatment within inpatient settings. There is little focus on outpatient services, where the psychiatric nurse can function as psychotherapist. Specific roles of one outpatient nurse therapist are outlined. Concrete guidelines in terms of supervision, support, and self-exploration are delineated for implementation by the nurse as outpatient psychotherapist."} {"id": "PMID:171392", "title": "Emergency discharges: their outcome.", "content": "This paper compares the short-term outcome of a group of seven patients released from an inpatient facility during an employee strike and a group of eight released at the optimal time according to the treating physicians. There was no difference in the outcome of the two groups, only two fifth of the entire cohort could be considered as doing well. The reasons for the findings are explored.", "contents": "Emergency discharges: their outcome. This paper compares the short-term outcome of a group of seven patients released from an inpatient facility during an employee strike and a group of eight released at the optimal time according to the treating physicians. There was no difference in the outcome of the two groups, only two fifth of the entire cohort could be considered as doing well. The reasons for the findings are explored."} {"id": "PMID:171393", "title": "Consultation to groups in conflict: some aspects of group design.", "content": "1. One should carefully consider the broad dynamics and deal with one's own feelings in performing the consultation. One should resist any pull to act hastily in setting up a group. 2. It must be determined if a group would be helpful in dealing with the problem. Then one must ascertain the desire for a group experience at all levels of the nursing hierarchy. Membership in a group should be by choice and not because of obligation or coercion. 3. The boundaries of the group should be worked out after careful evaluation of the problem. This should include discussion with any potential participants about the desire for a group and about issues of membership and other boundary decisions such as time and place. If the boundaries and responsibilities of membership cannot be agreed upon by the consultant and members, then it is far more responsible not to conduct a group. 4. The task of the group should be defined and clear to the members and be consistent with the desired output of the group. In a group in conflict, there should be a defined primary task, that of dealing with any issues related to the understanding of this conflict. It follows that the role function os the consultant must be carefully defined. 5. To do effective work, the consultant must be seen as independent of the ward authority. One should consider with utmost caution any individual consultation with group members, as this may limit the consultant's effectiveness in dealing with the whole group. The consequences of allowing the ward authority to attend group meetings should be thought through carefully as this will greatly increase the complexity of any experience.", "contents": "Consultation to groups in conflict: some aspects of group design. 1. One should carefully consider the broad dynamics and deal with one's own feelings in performing the consultation. One should resist any pull to act hastily in setting up a group. 2. It must be determined if a group would be helpful in dealing with the problem. Then one must ascertain the desire for a group experience at all levels of the nursing hierarchy. Membership in a group should be by choice and not because of obligation or coercion. 3. The boundaries of the group should be worked out after careful evaluation of the problem. This should include discussion with any potential participants about the desire for a group and about issues of membership and other boundary decisions such as time and place. If the boundaries and responsibilities of membership cannot be agreed upon by the consultant and members, then it is far more responsible not to conduct a group. 4. The task of the group should be defined and clear to the members and be consistent with the desired output of the group. In a group in conflict, there should be a defined primary task, that of dealing with any issues related to the understanding of this conflict. It follows that the role function os the consultant must be carefully defined. 5. To do effective work, the consultant must be seen as independent of the ward authority. One should consider with utmost caution any individual consultation with group members, as this may limit the consultant's effectiveness in dealing with the whole group. The consequences of allowing the ward authority to attend group meetings should be thought through carefully as this will greatly increase the complexity of any experience."} {"id": "PMID:171396", "title": "The hallucinating patient and nursing intervention.", "content": "This paper has been concerned with a patient's problematic behavior pattern, namely hallucinations. The social and dynamic significance of the behavior for the individual have been explored and analyzed and a formulation of possible developmental processes influencing the patient to utilize hallucinations has been discussed. On the basis of these analyses, formulations for a psychiatric nursing treatment plan of intervention have been presented. In conclusion, it is well to bear in mind that the schizophrenic patient, who is hallucinating, is striving to communicate in as clear and straightforward a way as he knows, the nature of his anxieties and experiences, despite how radically different they are from the nurse's, with speech content that is diffucult to follow. Thus, with this understanding, it behooves us as nurses to intervene accordingly and \"decode\" the hallucinated messages and thereby assist in breaking into the third stage in the evolutionary cycle of a psychosis, as cited by R.D. Laing: Stage 1 = Good (me); Stage 2 = Bad (me); Stage 3 = Mad (not me).", "contents": "The hallucinating patient and nursing intervention. This paper has been concerned with a patient's problematic behavior pattern, namely hallucinations. The social and dynamic significance of the behavior for the individual have been explored and analyzed and a formulation of possible developmental processes influencing the patient to utilize hallucinations has been discussed. On the basis of these analyses, formulations for a psychiatric nursing treatment plan of intervention have been presented. In conclusion, it is well to bear in mind that the schizophrenic patient, who is hallucinating, is striving to communicate in as clear and straightforward a way as he knows, the nature of his anxieties and experiences, despite how radically different they are from the nurse's, with speech content that is diffucult to follow. Thus, with this understanding, it behooves us as nurses to intervene accordingly and \"decode\" the hallucinated messages and thereby assist in breaking into the third stage in the evolutionary cycle of a psychosis, as cited by R.D. Laing: Stage 1 = Good (me); Stage 2 = Bad (me); Stage 3 = Mad (not me)."} {"id": "PMID:171401", "title": "The effect of inhibition of prostaglandin synthesis on ovarian hypertrophy in the rat.", "content": "Aspirin and indomethacin, inhibitors of prostaglandin biosynthesis, were utilized to determine the role of prostaglandins (PGs) in ovarian weight gain in rats following unilateral ovariectomy or treatment with PMSG. After unilateral ovariectomy, the compensatory ovarian hypertrophy was 185-0% compared with 139-8% and 97-5% in rats treated with indomethacin and aspirin, respectively. The adrenal weights in rats treated with aspirin were also reduced significantly. Administration of PGE2 or PGF2alpha with aspirin reversed the effect of aspirin on the adrenals but had no effect on the ovarian weight. Indomethacin and aspirin treatment of animals injected with PMSG also reduced the ovarian weight gain. If 100 mug PGE2 were given twice daily, this effect was reversed in both groups but thrice daily administration had no effect on rats receiving aspirin. In PMSG-treated rats, 100 mug PGF2alpha twice daily did not reverse the effect of indomethacin and aspirin, and actually enhanced the effect of aspirin.", "contents": "The effect of inhibition of prostaglandin synthesis on ovarian hypertrophy in the rat. Aspirin and indomethacin, inhibitors of prostaglandin biosynthesis, were utilized to determine the role of prostaglandins (PGs) in ovarian weight gain in rats following unilateral ovariectomy or treatment with PMSG. After unilateral ovariectomy, the compensatory ovarian hypertrophy was 185-0% compared with 139-8% and 97-5% in rats treated with indomethacin and aspirin, respectively. The adrenal weights in rats treated with aspirin were also reduced significantly. Administration of PGE2 or PGF2alpha with aspirin reversed the effect of aspirin on the adrenals but had no effect on the ovarian weight. Indomethacin and aspirin treatment of animals injected with PMSG also reduced the ovarian weight gain. If 100 mug PGE2 were given twice daily, this effect was reversed in both groups but thrice daily administration had no effect on rats receiving aspirin. In PMSG-treated rats, 100 mug PGF2alpha twice daily did not reverse the effect of indomethacin and aspirin, and actually enhanced the effect of aspirin."} {"id": "PMID:171402", "title": "Cytoplasmic oestradiol-binding sites and their relationship to oestradiol content in the endometrium of cattle.", "content": "Twenty-three cows and heifers were killed at known times during the oestrous cycle or during the first 35 days of pregnancy. Duplicate cytosol preparations were made from the endometrium of each uterine horn and both the binding-site concentration and the oestradiol level were determined for each sample. During the cycle, the oestradiol concentration was only 0-2 to 1-7% of the concentration of binding sites which varied considerably between Days 19 and 5 (47,665 +/- 7538 sites/cell, mean +/- S.E.M.) and Days 6 to 18 (7060 +/- 444 sites/cell). The concentration of binding sites remained low in pregnant animals (6689 +/- 492), although the oestradiol concentration was high about 20 days after insemination, resulting in almost 14% of the sites being occupied. Five inseminated animals in which no conceptus was found when they were slaughtered 19 to 22 days later had low concentrations of binding sites but two animals had high levels of oestradiol with 13% and 15%, respectively, of their cytoplasmic sites being occupied. It is suggested that these animals had recently lost their conceptuses. Two ovariectomized cows and one non-cyclic animal contained high concentrations of oestradiol-binding sites in the uterine cytoplasm. No significant difference was found between the uterine horn adjacent to the ovary with the CL and the contralateral horn in early pregnancy or during the luteal phase of the oestrous cycle. An animal killed 1 week after parturition contained fourfold more sites in the involuting horn than in the opposite horn. It is suggested that progesterone plays a major role in regulating oestrogen-induced replacement of cytoplasmic binding sites.", "contents": "Cytoplasmic oestradiol-binding sites and their relationship to oestradiol content in the endometrium of cattle. Twenty-three cows and heifers were killed at known times during the oestrous cycle or during the first 35 days of pregnancy. Duplicate cytosol preparations were made from the endometrium of each uterine horn and both the binding-site concentration and the oestradiol level were determined for each sample. During the cycle, the oestradiol concentration was only 0-2 to 1-7% of the concentration of binding sites which varied considerably between Days 19 and 5 (47,665 +/- 7538 sites/cell, mean +/- S.E.M.) and Days 6 to 18 (7060 +/- 444 sites/cell). The concentration of binding sites remained low in pregnant animals (6689 +/- 492), although the oestradiol concentration was high about 20 days after insemination, resulting in almost 14% of the sites being occupied. Five inseminated animals in which no conceptus was found when they were slaughtered 19 to 22 days later had low concentrations of binding sites but two animals had high levels of oestradiol with 13% and 15%, respectively, of their cytoplasmic sites being occupied. It is suggested that these animals had recently lost their conceptuses. Two ovariectomized cows and one non-cyclic animal contained high concentrations of oestradiol-binding sites in the uterine cytoplasm. No significant difference was found between the uterine horn adjacent to the ovary with the CL and the contralateral horn in early pregnancy or during the luteal phase of the oestrous cycle. An animal killed 1 week after parturition contained fourfold more sites in the involuting horn than in the opposite horn. It is suggested that progesterone plays a major role in regulating oestrogen-induced replacement of cytoplasmic binding sites."} {"id": "PMID:171397", "title": "Never too old to climb.", "content": "This nurse-administrated program has added another dimension to the hospital environment. It provides a real challenge and opportunity for reaching out in planning and implementing a program for the elderly, long-term psychiatric hospitalized resident. It has been successful because of a sincere and dedicated staff who consistently communicated, verbally and non-verbally, that \"we cared\"--by listening, keeping open minds, establishing and maintaining an environment conducive to growth, acceptance, encouragement, social contacts, and creating a genuine relationship based on trust. It was through these media that we achieved a milestone with the new program. Demonstration of concern, patience and interest seemed to have been a motivating force which stimulated a desire to achieve optimum growth for a majority of the residents, which has affected every service in this hospital. The freedom to plan and execute, with administrative support, challenged staff, who reached out and grasped the opportunity to turn away from the traditional ways of providing care to new ways of improving and delivering quality care to the elderly, long-term psychiatric residents. This program has been in not, however, been a panacea for all residents. Assuming responsibility, freedom to make decisions and thoughts of leaving the hospital have been somewhat difficult adjustments for a few residents. As of December 1974, approximately 5 per cent of those placed in the community were returned to the structured environment of the hospital. The successes, however, have far outnumbered the adversities in that 34 have been discharged and three are ready to be discharged in the near future.", "contents": "Never too old to climb. This nurse-administrated program has added another dimension to the hospital environment. It provides a real challenge and opportunity for reaching out in planning and implementing a program for the elderly, long-term psychiatric hospitalized resident. It has been successful because of a sincere and dedicated staff who consistently communicated, verbally and non-verbally, that \"we cared\"--by listening, keeping open minds, establishing and maintaining an environment conducive to growth, acceptance, encouragement, social contacts, and creating a genuine relationship based on trust. It was through these media that we achieved a milestone with the new program. Demonstration of concern, patience and interest seemed to have been a motivating force which stimulated a desire to achieve optimum growth for a majority of the residents, which has affected every service in this hospital. The freedom to plan and execute, with administrative support, challenged staff, who reached out and grasped the opportunity to turn away from the traditional ways of providing care to new ways of improving and delivering quality care to the elderly, long-term psychiatric residents. This program has been in not, however, been a panacea for all residents. Assuming responsibility, freedom to make decisions and thoughts of leaving the hospital have been somewhat difficult adjustments for a few residents. As of December 1974, approximately 5 per cent of those placed in the community were returned to the structured environment of the hospital. The successes, however, have far outnumbered the adversities in that 34 have been discharged and three are ready to be discharged in the near future."} {"id": "PMID:171403", "title": "Termination of pregnancy after accelerated lactation in the rat. III. Effects of hormonal treatments.", "content": "The relationship was investigated of the hormones associated with pregnancy and lactation and the termination of pregnancy that occurs when rats mated at the post-partum oestrus are allowed to suckle a large litter after implantation. The primary cause for pregnancy termination was found to be an insufficient level of progesterone with the possible need for a primary or synergistic dose of oestrogen. The progesterone deficiency was not due to the high levels of prolactin present in nursing rats, since pregnancy termination could not be produced by prolactin administration in the absence of accelerated lactation, and could not be prevented by blocking prolactin secretion after accelerated lactation. Administration of LH to rats after accelerated lactation did prevent termination of pregnancy.", "contents": "Termination of pregnancy after accelerated lactation in the rat. III. Effects of hormonal treatments. The relationship was investigated of the hormones associated with pregnancy and lactation and the termination of pregnancy that occurs when rats mated at the post-partum oestrus are allowed to suckle a large litter after implantation. The primary cause for pregnancy termination was found to be an insufficient level of progesterone with the possible need for a primary or synergistic dose of oestrogen. The progesterone deficiency was not due to the high levels of prolactin present in nursing rats, since pregnancy termination could not be produced by prolactin administration in the absence of accelerated lactation, and could not be prevented by blocking prolactin secretion after accelerated lactation. Administration of LH to rats after accelerated lactation did prevent termination of pregnancy."} {"id": "PMID:171404", "title": "Rupture of ovarian follicles at ovulation.", "content": "The appearance of mammalian follicles at the time of ovulation has been described by numerous observers. Importance features to which attention has been directed are: changes in the vascularization of the follicle, the appearance of an avascular area known as the macula pellucida or stigma, the formation of small blood clots near the stigma and some extravasation of blood, and the rupture of the follicle at the stigma and exist of the oocyte and follicular fluid. The first major advance beyond this descriptive stage came with the demonstration that antral pressure does not increase prior to follicle rupture. This observation eliminated a number of hypotheses concerning ovulation and focused attention on the deterioration and weakening of the follicle wall at the stigma. That the follicle wall weakness prior to rupture is established beyond doubt by gross observations of its increased fragility during various manipulative procedures, by stress-strain measurements in vivo and in vitro, and by histological observations. Progressive weakening of the stigma region by thinning and degeneration is a fundamental aspect of the preovulatory maturation of follicles, and it would appear to be a necessary prerequisite to rupture.", "contents": "Rupture of ovarian follicles at ovulation. The appearance of mammalian follicles at the time of ovulation has been described by numerous observers. Importance features to which attention has been directed are: changes in the vascularization of the follicle, the appearance of an avascular area known as the macula pellucida or stigma, the formation of small blood clots near the stigma and some extravasation of blood, and the rupture of the follicle at the stigma and exist of the oocyte and follicular fluid. The first major advance beyond this descriptive stage came with the demonstration that antral pressure does not increase prior to follicle rupture. This observation eliminated a number of hypotheses concerning ovulation and focused attention on the deterioration and weakening of the follicle wall at the stigma. That the follicle wall weakness prior to rupture is established beyond doubt by gross observations of its increased fragility during various manipulative procedures, by stress-strain measurements in vivo and in vitro, and by histological observations. Progressive weakening of the stigma region by thinning and degeneration is a fundamental aspect of the preovulatory maturation of follicles, and it would appear to be a necessary prerequisite to rupture."} {"id": "PMID:171405", "title": "Interrelationships between prostaglandins, cyclic AMP and steroids in ovulation.", "content": "Ovulation is a complex phenomenon, involving a series of biochemical events within the ovary, leading to the rupture of the follicle. This paper summarizes recent studies in our laboratory of some of these biochemical changes using the rabbit as an experimental model. It has been shown in our laboratory that isolated Graafian follicles obtained from oestrous rabbits synthesize steroids and cyclic AMP when incubated in vitro. Luteinizing hormone added to the incubation medium increased steroidogenesis and cyclic AMP synthesis many fold. When follicles were isolated from rabbits at different times following the ovulatory stimulus (mating or HCG injection) it was found that the in vitro response to LH in terms of steroidogenesis and cylcic AMP synthesis was lost as ovulation approached. In contrast, when prostaglandins (PGF and PGE) were measured in rabbit Graafian follicles it was found that the PGF and PGE levels increased as ovulation approached. From these data and from reports in the literature, we have developed a hypothetical model for ovulation in the rabbit which may help in a better understanding of the ovulatory process.", "contents": "Interrelationships between prostaglandins, cyclic AMP and steroids in ovulation. Ovulation is a complex phenomenon, involving a series of biochemical events within the ovary, leading to the rupture of the follicle. This paper summarizes recent studies in our laboratory of some of these biochemical changes using the rabbit as an experimental model. It has been shown in our laboratory that isolated Graafian follicles obtained from oestrous rabbits synthesize steroids and cyclic AMP when incubated in vitro. Luteinizing hormone added to the incubation medium increased steroidogenesis and cyclic AMP synthesis many fold. When follicles were isolated from rabbits at different times following the ovulatory stimulus (mating or HCG injection) it was found that the in vitro response to LH in terms of steroidogenesis and cylcic AMP synthesis was lost as ovulation approached. In contrast, when prostaglandins (PGF and PGE) were measured in rabbit Graafian follicles it was found that the PGF and PGE levels increased as ovulation approached. From these data and from reports in the literature, we have developed a hypothetical model for ovulation in the rabbit which may help in a better understanding of the ovulatory process."} {"id": "PMID:171406", "title": "A phlogistic function of PGE1 in calcium pyrophosphate dihydrate crystal-induced inflammation.", "content": "Promotion of calcium pyrophosphate dihydrate (CaPPD) crystal-induced inflammation by prostaglandin (PG) E1 has been demonstrated by two new techniques: (1) Rats deficient in essential fatty acids, biological precursors of PG, developed less footpad swelling than did normal rats following injections of unheated CaPPD. Addition of one ng of PGE1 to these crystals resulted in normal swelling. (2) This phlogistic effect of PGE1 was also demonstrated in normal rats fed a normal dietwho received injections of CaPPD crystals heated to 200 degrees C for three hours. The heated crystals induced less footpad swelling than did unheated crystals. When one ng of PGE1 was added to the suspensions of heated crystals the resultant swelling approximated that obtained by unheated crystals. The possible role of PGE1 in mediating CaPPD crystal-induced inflammation is suggested. An analysis of urate and CaPPD crytal-induced inflammation is presented with comments setting forth the concept that these metabolic crystal disorders are membrane diseases.", "contents": "A phlogistic function of PGE1 in calcium pyrophosphate dihydrate crystal-induced inflammation. Promotion of calcium pyrophosphate dihydrate (CaPPD) crystal-induced inflammation by prostaglandin (PG) E1 has been demonstrated by two new techniques: (1) Rats deficient in essential fatty acids, biological precursors of PG, developed less footpad swelling than did normal rats following injections of unheated CaPPD. Addition of one ng of PGE1 to these crystals resulted in normal swelling. (2) This phlogistic effect of PGE1 was also demonstrated in normal rats fed a normal dietwho received injections of CaPPD crystals heated to 200 degrees C for three hours. The heated crystals induced less footpad swelling than did unheated crystals. When one ng of PGE1 was added to the suspensions of heated crystals the resultant swelling approximated that obtained by unheated crystals. The possible role of PGE1 in mediating CaPPD crystal-induced inflammation is suggested. An analysis of urate and CaPPD crytal-induced inflammation is presented with comments setting forth the concept that these metabolic crystal disorders are membrane diseases."} {"id": "PMID:171407", "title": "Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis.", "content": "The pseudogout syndrome is usually associated with radiographic evidence of articular cartilage calcification. Eight patients who had joints containing calcium pyrophosphate dihydrate crystals were studied. Extensive radiographic evaluation was obtained in seven patients and a limited evaluation in the other. None had evidence of chondrocalcinosis. Six had distinctive radiographic abnormalities of the wrists consisting of radiocarpal joint space narrowing and sclerosis, and subchondral cystic degeneration of the carpal bones. We conclude that calcium pyrophosphate dihydrate deposition disease and pseudogout can occur without radiographic evidence of chondrocalcinosis and that the diagnosis can be suggested by characteristic radiographic abnormalities of the wrists.", "contents": "Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis. The pseudogout syndrome is usually associated with radiographic evidence of articular cartilage calcification. Eight patients who had joints containing calcium pyrophosphate dihydrate crystals were studied. Extensive radiographic evaluation was obtained in seven patients and a limited evaluation in the other. None had evidence of chondrocalcinosis. Six had distinctive radiographic abnormalities of the wrists consisting of radiocarpal joint space narrowing and sclerosis, and subchondral cystic degeneration of the carpal bones. We conclude that calcium pyrophosphate dihydrate deposition disease and pseudogout can occur without radiographic evidence of chondrocalcinosis and that the diagnosis can be suggested by characteristic radiographic abnormalities of the wrists."} {"id": "PMID:171408", "title": "Predominance of synovial fluid lymphocytes in early rheumatoid arthritis.", "content": "Evaluation of 158 synovial fluids, mainly from patients with rheumatoid arthritis (RA) and the crystal deposition fiseases (CDD), revealed differences in the differential white blood count and numbers of cytoplasmic inclusion bodies (CIB) present. Lymphocytes and CIB were increased in RA, suggesting a different pathologic mechanism from that of CDD. Lymphocyte-like cells contained CIB implying phagocytic capability. Lymphocytes were the initial predominant cell type in RA of less than six weeks disease duration. Later polymorphonuclear leukocytes increased, possibily representing a secondary non-specific inflammatory response similar to that seen in CDD.", "contents": "Predominance of synovial fluid lymphocytes in early rheumatoid arthritis. Evaluation of 158 synovial fluids, mainly from patients with rheumatoid arthritis (RA) and the crystal deposition fiseases (CDD), revealed differences in the differential white blood count and numbers of cytoplasmic inclusion bodies (CIB) present. Lymphocytes and CIB were increased in RA, suggesting a different pathologic mechanism from that of CDD. Lymphocyte-like cells contained CIB implying phagocytic capability. Lymphocytes were the initial predominant cell type in RA of less than six weeks disease duration. Later polymorphonuclear leukocytes increased, possibily representing a secondary non-specific inflammatory response similar to that seen in CDD."} {"id": "PMID:171409", "title": "Isolation of foamy virus from rhesus, African green and cynomolgus monkey Leukocytes.", "content": "Foamy virus (FV) was recovered regularly from the leukocyte of rhesus and cynomolgus monkeys and somewhat less often from African green monkey leukocytes. Virus was found in virtually all organs of experimentally infected rhesus monkeys. No illness or pathologic abnormalities were noted in these animals or in any of the naturally infected animals in spite of the prolonged period of viral persistence in various organs and tissues.", "contents": "Isolation of foamy virus from rhesus, African green and cynomolgus monkey Leukocytes. Foamy virus (FV) was recovered regularly from the leukocyte of rhesus and cynomolgus monkeys and somewhat less often from African green monkey leukocytes. Virus was found in virtually all organs of experimentally infected rhesus monkeys. No illness or pathologic abnormalities were noted in these animals or in any of the naturally infected animals in spite of the prolonged period of viral persistence in various organs and tissues."} {"id": "PMID:171424", "title": "Herpesvirus antibodies and antigens in patients with cervical anaplasia and in controls.", "content": "Antibody activity to herpesvirus hominis type 2 (HVH-2) in 151 women cured of cervical carcinoma (60 in situ, 91 invasive) and in 106 controls differed significantly, especially between the in situ (73%) and control (17%) groups. Sera of 57 patients with cervical atypia showed an increased antibody activity to HVH-2 (58%), compared with that of the 57 matched controls (23%). Antibodies to cytomegalovirus (CMV) were detected more frequently in sera of women with atypia (61%) than in sera of women with cervical disorders other than atypia (42%) or in sera of healthy controls (33%). HVH antigens were present in cervical cells from patients with atypia and from matched controls. Not only exfoliated (imprints) but also cultured and cocultured cervical cells contained HVH antigens; there was no correlation between antigen positivity and antibody activity to HVH-2. Our data further supported the association between HVH-2 and cervical anaplasia and indicated that CMV may also be implicated in its etiology.", "contents": "Herpesvirus antibodies and antigens in patients with cervical anaplasia and in controls. Antibody activity to herpesvirus hominis type 2 (HVH-2) in 151 women cured of cervical carcinoma (60 in situ, 91 invasive) and in 106 controls differed significantly, especially between the in situ (73%) and control (17%) groups. Sera of 57 patients with cervical atypia showed an increased antibody activity to HVH-2 (58%), compared with that of the 57 matched controls (23%). Antibodies to cytomegalovirus (CMV) were detected more frequently in sera of women with atypia (61%) than in sera of women with cervical disorders other than atypia (42%) or in sera of healthy controls (33%). HVH antigens were present in cervical cells from patients with atypia and from matched controls. Not only exfoliated (imprints) but also cultured and cocultured cervical cells contained HVH antigens; there was no correlation between antigen positivity and antibody activity to HVH-2. Our data further supported the association between HVH-2 and cervical anaplasia and indicated that CMV may also be implicated in its etiology."} {"id": "PMID:171425", "title": "Suppression of spontaneous in vitro transformation of autologous leukocytes by plasma from convalescent and postconvalescent infectious mononucleosis patients.", "content": "All 14 plasma samples from 13 convalescent and postconvalescent infectious mononucleosis (IM) patients suppressed the spontaneous in vitro transformation of autologous leukocytes. In contrast, only 2 of 8 plasma samples from patients with acute IM suppressed this transformation. All 7 patients whose blood was tested both in the acute and convalescent or postconvalescent phases of IM showed either a conversion in transformation suppression status from negative to positive or an increase in the strength of transformation suppression. Thus recovery from IM appeared to be associated with the ability of plasma to suppress the in vitro spontaneous transformation of autologous leukocytes.", "contents": "Suppression of spontaneous in vitro transformation of autologous leukocytes by plasma from convalescent and postconvalescent infectious mononucleosis patients. All 14 plasma samples from 13 convalescent and postconvalescent infectious mononucleosis (IM) patients suppressed the spontaneous in vitro transformation of autologous leukocytes. In contrast, only 2 of 8 plasma samples from patients with acute IM suppressed this transformation. All 7 patients whose blood was tested both in the acute and convalescent or postconvalescent phases of IM showed either a conversion in transformation suppression status from negative to positive or an increase in the strength of transformation suppression. Thus recovery from IM appeared to be associated with the ability of plasma to suppress the in vitro spontaneous transformation of autologous leukocytes."} {"id": "PMID:171426", "title": "Loss of ability to synthesize collagen in fibroblasts transformed by rous sarcoma virus.", "content": "Transformation of chick embryo fibroblasts by Rous sarcoma virus inhibited their ability to synthesize collagen. Kinetic experiments showed that 72 hours after infection, collagen synthesis was reduced by 90%. Nontransforming Rous-associated viruses did not inhibit collagen synthesis. The inhibition resulted from the failure of the cells to synthesize collagen polypeptides rather than from a decrease in the activity of prolyl hydroxylase; the levels of prolyl hydroxylase were fourfold those in uninfected cells. The addition of dibutyryl cyclic AMP and theophylline, alone or together, did not restore collagen synthesis.", "contents": "Loss of ability to synthesize collagen in fibroblasts transformed by rous sarcoma virus. Transformation of chick embryo fibroblasts by Rous sarcoma virus inhibited their ability to synthesize collagen. Kinetic experiments showed that 72 hours after infection, collagen synthesis was reduced by 90%. Nontransforming Rous-associated viruses did not inhibit collagen synthesis. The inhibition resulted from the failure of the cells to synthesize collagen polypeptides rather than from a decrease in the activity of prolyl hydroxylase; the levels of prolyl hydroxylase were fourfold those in uninfected cells. The addition of dibutyryl cyclic AMP and theophylline, alone or together, did not restore collagen synthesis."} {"id": "PMID:171427", "title": "Neoplasms in strains of splenectomized mice after a single 7,12-dimethylbenz[alpha]anthracene treatment.", "content": "The effects of splenectomy on carcinogenesis by a single 10-mg dose of 7,12-dimethylbenz[alpha]anthracene (DMBA) given in olive oil by gavage was tested on BTOs, C57BL/60s, C3H/HeOs, and BALB/cOs mice. The splenectomy, performed a week before the DMBA was given, did not affect physical status or the incidence of acute toxic death of animals. DMBA-treated animals developed neoplasms at a significantly higher rate than did untreated mice. Splenectomy did not influence the overall incidence of neoplasms. Observed tumors in DMBA-treated groups were those of skin, forestomach, colon, liver, lung, adrenal, ovary, breast, hematopoietic-lymphoreticular system, and vascular system, depending on the strain. Types of DMBA-treated neoplasms were affected by prior splenectomy, depending on the strain: Splenectomy inhibited lung adenomas in BALB/cOs females and hepatomas in C57BL/60s females; splenectomy enhanced skin neoplasms in C57BL/60s and squamous cell carcinoma of the forestomach in BTOs males. The most significant change was in the incidence of the group of lymphomas. Myelogenous leukemia was increased in DMBA-treated groups of all strains, but splenectomy inhibited the development of this type of lymphoma.", "contents": "Neoplasms in strains of splenectomized mice after a single 7,12-dimethylbenz[alpha]anthracene treatment. The effects of splenectomy on carcinogenesis by a single 10-mg dose of 7,12-dimethylbenz[alpha]anthracene (DMBA) given in olive oil by gavage was tested on BTOs, C57BL/60s, C3H/HeOs, and BALB/cOs mice. The splenectomy, performed a week before the DMBA was given, did not affect physical status or the incidence of acute toxic death of animals. DMBA-treated animals developed neoplasms at a significantly higher rate than did untreated mice. Splenectomy did not influence the overall incidence of neoplasms. Observed tumors in DMBA-treated groups were those of skin, forestomach, colon, liver, lung, adrenal, ovary, breast, hematopoietic-lymphoreticular system, and vascular system, depending on the strain. Types of DMBA-treated neoplasms were affected by prior splenectomy, depending on the strain: Splenectomy inhibited lung adenomas in BALB/cOs females and hepatomas in C57BL/60s females; splenectomy enhanced skin neoplasms in C57BL/60s and squamous cell carcinoma of the forestomach in BTOs males. The most significant change was in the incidence of the group of lymphomas. Myelogenous leukemia was increased in DMBA-treated groups of all strains, but splenectomy inhibited the development of this type of lymphoma."} {"id": "PMID:171428", "title": "Simian virus tumor antigen: a virus-specific and preexisting cell protein.", "content": "The tumor (T) antigen of simian virus 40 (SV40)-transformed SV3T3 cells was immune precipitated with T antiserum obtained from hamsters bearing SV40-induced tumors and with rabbit antiserum to hamster cells. The resulting antigen-double antibody complexes were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Host components of SV40 T antigen with molecular weights of 70,000 and 30,000 were detected.", "contents": "Simian virus tumor antigen: a virus-specific and preexisting cell protein. The tumor (T) antigen of simian virus 40 (SV40)-transformed SV3T3 cells was immune precipitated with T antiserum obtained from hamsters bearing SV40-induced tumors and with rabbit antiserum to hamster cells. The resulting antigen-double antibody complexes were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Host components of SV40 T antigen with molecular weights of 70,000 and 30,000 were detected."} {"id": "PMID:171429", "title": "Histologic and electron microscopy observations on diethylnitrosamine-induced hepatomas in small aquarium fish (Oryzias latipes).", "content": "Liver neoplasms were induced in medakas (Oryzias latipes) by the addition of diethylnitrosamine (DENA) to their aquarium water at levels of 15-135 ppm for 8 weeks. After 13 weeks, 21 to 32 fish had developed hepatomas. Medakas are useful for further studies because they are highly susceptible to the carcinogenic effect of DENA, and the time for tumor induction is relatively short. Histologic type differed in the lesions of different fish and also within individual tumors. Some were typical trabecular hepatomas, others were anaplastic hepatomas or cholangiomas, or mixtures of these. Electron microscopy revealed an extensive rough-surfaced endoplasmic reticulum in a lamellar pattern, many mitochondria, and several round lysosomes in tumor cells. A few fat droplets with occasional crystalline ghosts were sometimes in the cytoplasm. The Golgi apparatus was not conspicuous. Some cells had highly developed microvilli that showed differentiation toward structures resembling bile capillaries.", "contents": "Histologic and electron microscopy observations on diethylnitrosamine-induced hepatomas in small aquarium fish (Oryzias latipes). Liver neoplasms were induced in medakas (Oryzias latipes) by the addition of diethylnitrosamine (DENA) to their aquarium water at levels of 15-135 ppm for 8 weeks. After 13 weeks, 21 to 32 fish had developed hepatomas. Medakas are useful for further studies because they are highly susceptible to the carcinogenic effect of DENA, and the time for tumor induction is relatively short. Histologic type differed in the lesions of different fish and also within individual tumors. Some were typical trabecular hepatomas, others were anaplastic hepatomas or cholangiomas, or mixtures of these. Electron microscopy revealed an extensive rough-surfaced endoplasmic reticulum in a lamellar pattern, many mitochondria, and several round lysosomes in tumor cells. A few fat droplets with occasional crystalline ghosts were sometimes in the cytoplasm. The Golgi apparatus was not conspicuous. Some cells had highly developed microvilli that showed differentiation toward structures resembling bile capillaries."} {"id": "PMID:171430", "title": "Murine oncornavirus activation in the pancreas during infection with Venezuelan equine encephalitis virus.", "content": "Electron microscopic studies of the pancreases of 3-week-old ICR Swiss mice infected with Venezuelan equine encephalitis virus and killed 6 days post inoculation (at which time they were moribund) indicated significantly more type-C particles than were found in uninfected controls. This phenomenon was apparently possible because of the microanatomy of the pancreas, in which interstital spaces allowed accumulation of virus particles.", "contents": "Murine oncornavirus activation in the pancreas during infection with Venezuelan equine encephalitis virus. Electron microscopic studies of the pancreases of 3-week-old ICR Swiss mice infected with Venezuelan equine encephalitis virus and killed 6 days post inoculation (at which time they were moribund) indicated significantly more type-C particles than were found in uninfected controls. This phenomenon was apparently possible because of the microanatomy of the pancreas, in which interstital spaces allowed accumulation of virus particles."} {"id": "PMID:171432", "title": "Differential response to cytochalasin B among cells transformed by DNA and RNA tumor viruses.", "content": "Mouse, hamster, rat, human, and chick cells were transformed by RNA and DNA tumor viruses: simian virus 40, adenovirus type 7, Kirsten mouse sarcoma virus (Ki-MuSV), Moloney mouse sarcoma virus, and Rous sarcoma virus. All cultures of transformed cells grew to high concentration densities. Normal and transformed cells were treated with cytochalasin B (CB) at concentrations preventing cytoplasmic cleavage. Cells altered by DNA tumor viruses responded to CB with numerous nuclear divisions resulting in highly multinucleated cells. All but one line of cells transformed by RNA tumor viruses responded to CB with usually only one and occasionally two nuclear divisions. Only binucleated cells were formed. One clone of CB-treated BALB/c mouse embryo fibroblasts transformed by Ki-MuSV showed numerous cells with four and five nuclei. HOWEVER, IN CONTRASt to cells transformed by DNA viruses, few cells had seven or more nuclei. These results suggest that, in the presence of CB, cells transformed by DNA tumor viruses show uncontrolled nuclear division, whereas cells tranformed by RNA tumor viruses show controlled nuclear division.", "contents": "Differential response to cytochalasin B among cells transformed by DNA and RNA tumor viruses. Mouse, hamster, rat, human, and chick cells were transformed by RNA and DNA tumor viruses: simian virus 40, adenovirus type 7, Kirsten mouse sarcoma virus (Ki-MuSV), Moloney mouse sarcoma virus, and Rous sarcoma virus. All cultures of transformed cells grew to high concentration densities. Normal and transformed cells were treated with cytochalasin B (CB) at concentrations preventing cytoplasmic cleavage. Cells altered by DNA tumor viruses responded to CB with numerous nuclear divisions resulting in highly multinucleated cells. All but one line of cells transformed by RNA tumor viruses responded to CB with usually only one and occasionally two nuclear divisions. Only binucleated cells were formed. One clone of CB-treated BALB/c mouse embryo fibroblasts transformed by Ki-MuSV showed numerous cells with four and five nuclei. HOWEVER, IN CONTRASt to cells transformed by DNA viruses, few cells had seven or more nuclei. These results suggest that, in the presence of CB, cells transformed by DNA tumor viruses show uncontrolled nuclear division, whereas cells tranformed by RNA tumor viruses show controlled nuclear division."} {"id": "PMID:171433", "title": "Effect of adeno-associated virus on cancer expression by herpesvirus-transformed hamster cells.", "content": "Infection of herpes simplex virus type-2-transformed hamster tumor cells with adeno-associated virus type 1 before inoculation into hamsters specifically delayed the appearance of palpable tumors and increased the survival time of the animals. The data indicated that a defective virus of humans can influence cancer expression by a virus-transformed cell.", "contents": "Effect of adeno-associated virus on cancer expression by herpesvirus-transformed hamster cells. Infection of herpes simplex virus type-2-transformed hamster tumor cells with adeno-associated virus type 1 before inoculation into hamsters specifically delayed the appearance of palpable tumors and increased the survival time of the animals. The data indicated that a defective virus of humans can influence cancer expression by a virus-transformed cell."} {"id": "PMID:171434", "title": "Inhibition of in vitro growth of lymphoma cells by macrophages from tumor-bearing mice.", "content": "Spleen cells from C57BL/6 mice bearing primary tumors induced by the Moloney strain of murine sarcoma virus (MuSV) strongly inhibited the uptake of tritiated thymidine (3H-TDR) by RBL-5 lymphoma cells in a 48-hour growth-inhibition assay (GIA). This activity was first detected 7 days after MuSV was injected; it peaked at 14 days, and was usually no longer detectable after 18-21 days. It could be detected at effector cell/target cell ratios between 20:1 and 5:1, at which normal spleen cells had a growth-promoting effect. The effector cells in the GIA were not T cells, and various depletion experiments suggested that they were macrophages. Macrophages of a purity of over 95% were obtained in the glass-adherent fraction of thioglycollate-induced peritoneal exudate cells (PEC). PEC were growth inhibitory when obtained from either normal or MuSV tumor-bearing mice. However, at effector cell/target ratios of 2.5:1, only PEC from MuSV tumor-bearing mice had an effect; PEC from normal mice were inactive. Activity of spleen cells in the GIA appeared distinct from T-cell-dependent specific cytotoxicity, which was not affected by removal of macrophages. Activity in the GIA was nonspecific, and target cells which do not cross-react with RBL-5 cells were equally inhibited. Furthermore, spleen cells from mice bearing primary tumors induced by 3-methylcholanthrene were also fully active against RBL-5 cells. Supernatants from spleen cell cultures obtained from mice 14 days post injection with MuSV also inhibited the incorporation of 3H-TDR by RBL-5 cells in vitro. However, this effect seemed to be an artifact, since the tumor cells proliferated equally well in the presence or absence of the supernatants. In contrast, the direct effect of spleen cells from MuSV tumor-bearing mice was reflected both by an inhibition of cell proliferation and by inhibition of 3H-TDR incorporation.", "contents": "Inhibition of in vitro growth of lymphoma cells by macrophages from tumor-bearing mice. Spleen cells from C57BL/6 mice bearing primary tumors induced by the Moloney strain of murine sarcoma virus (MuSV) strongly inhibited the uptake of tritiated thymidine (3H-TDR) by RBL-5 lymphoma cells in a 48-hour growth-inhibition assay (GIA). This activity was first detected 7 days after MuSV was injected; it peaked at 14 days, and was usually no longer detectable after 18-21 days. It could be detected at effector cell/target cell ratios between 20:1 and 5:1, at which normal spleen cells had a growth-promoting effect. The effector cells in the GIA were not T cells, and various depletion experiments suggested that they were macrophages. Macrophages of a purity of over 95% were obtained in the glass-adherent fraction of thioglycollate-induced peritoneal exudate cells (PEC). PEC were growth inhibitory when obtained from either normal or MuSV tumor-bearing mice. However, at effector cell/target ratios of 2.5:1, only PEC from MuSV tumor-bearing mice had an effect; PEC from normal mice were inactive. Activity of spleen cells in the GIA appeared distinct from T-cell-dependent specific cytotoxicity, which was not affected by removal of macrophages. Activity in the GIA was nonspecific, and target cells which do not cross-react with RBL-5 cells were equally inhibited. Furthermore, spleen cells from mice bearing primary tumors induced by 3-methylcholanthrene were also fully active against RBL-5 cells. Supernatants from spleen cell cultures obtained from mice 14 days post injection with MuSV also inhibited the incorporation of 3H-TDR by RBL-5 cells in vitro. However, this effect seemed to be an artifact, since the tumor cells proliferated equally well in the presence or absence of the supernatants. In contrast, the direct effect of spleen cells from MuSV tumor-bearing mice was reflected both by an inhibition of cell proliferation and by inhibition of 3H-TDR incorporation."} {"id": "PMID:171435", "title": "Local antitumor activity of a primary and an anamnestic response to a syngeneic guinea pig hepatoma.", "content": "After intradermal (id) injection, the line-10 hepatoma grew progressively in nonimmune guinea pigs, whereas the line-1 hepatoma grew for approximately 2 weeks, developed central necrosis, ulcerated, and regressed. Growth of the line-10 hepatoma was suppressed when line-10 hepatoma cells were mixed with antigenically distinct line-1 hepatoma cells before id injection into syngeneic strain-2 guinea pigs. Mixture of line-10 with irradiated line-1 or viable strain-2 embryo cells did not inhibit tumor growth. Preimmunization of recipients to line-1 cells abrogated the suppression of tumor growth from mixtures of line-1 and line-10.", "contents": "Local antitumor activity of a primary and an anamnestic response to a syngeneic guinea pig hepatoma. After intradermal (id) injection, the line-10 hepatoma grew progressively in nonimmune guinea pigs, whereas the line-1 hepatoma grew for approximately 2 weeks, developed central necrosis, ulcerated, and regressed. Growth of the line-10 hepatoma was suppressed when line-10 hepatoma cells were mixed with antigenically distinct line-1 hepatoma cells before id injection into syngeneic strain-2 guinea pigs. Mixture of line-10 with irradiated line-1 or viable strain-2 embryo cells did not inhibit tumor growth. Preimmunization of recipients to line-1 cells abrogated the suppression of tumor growth from mixtures of line-1 and line-10."} {"id": "PMID:171441", "title": "DNA polymerases in polyoma virus-infected mouse kidney cells.", "content": "Infection of arrested mouse kidney cells by polyoma virus results in the induction of the cellular 6-8S DNA polymerase activity. Levels of this enzyme increase two- to threefold in the cytoplasm but seven- to tenfold in nuclei and nuclear extract, suggesting an accumulation of the enzyme in the nucleus. Experiments using the inhibitor of DNA synthesis, fluordeoxyuridine, indicate that this accumulation is linked to active DNA synthesis. The activity and cellular distribution of the small 3.4S DNA polymerase remains unchanged.", "contents": "DNA polymerases in polyoma virus-infected mouse kidney cells. Infection of arrested mouse kidney cells by polyoma virus results in the induction of the cellular 6-8S DNA polymerase activity. Levels of this enzyme increase two- to threefold in the cytoplasm but seven- to tenfold in nuclei and nuclear extract, suggesting an accumulation of the enzyme in the nucleus. Experiments using the inhibitor of DNA synthesis, fluordeoxyuridine, indicate that this accumulation is linked to active DNA synthesis. The activity and cellular distribution of the small 3.4S DNA polymerase remains unchanged."} {"id": "PMID:171442", "title": "Effect of hypertonic conditions on protein synthesis in cells productively infected with simian virus 40.", "content": "Hypertonic medium selectively suppressed the synthesis of most host cell polypeptides relative to the synthesis of simian virus 40 capsid polypeptides and a minority of cellular polypeptides, notably histones. Under optimal hypertonic conditions, the synthesis of the major capsid polypeptide (VP1) is enhanced about sevenfold relative to host polypeptide synthesis. Because of the small amounts of the other nonhistone capsid polypeptides (VP2) and VP3) present in cell lysates, it was difficult to quantitate the extent, if any, of their enhancement. The maintenance of the restricted pattern of protein synthesis caused by hypertonic medium was dependent on continual peptide chain initiations. The resistance of viral protein synthesis to hypertonic conditions provides a means of detecting relatively low levels of intracellular viral protein synthesis. Analysis of the specific activity of the acid-soluble [3H]lysine pool indicated that the rate of incorporation of [3H]lysine into protein was an overestimation of the actual rate of overall protein synthesis occurring in cells exposed to hypertonic as compared to isotonic conditions. Since it is likely that both cellular and viral protein synthesis draw lysine from a single pool, this change in pool specific activity does not affect the analysis of relative rates of protein synthesis at a given level of tonicity.", "contents": "Effect of hypertonic conditions on protein synthesis in cells productively infected with simian virus 40. Hypertonic medium selectively suppressed the synthesis of most host cell polypeptides relative to the synthesis of simian virus 40 capsid polypeptides and a minority of cellular polypeptides, notably histones. Under optimal hypertonic conditions, the synthesis of the major capsid polypeptide (VP1) is enhanced about sevenfold relative to host polypeptide synthesis. Because of the small amounts of the other nonhistone capsid polypeptides (VP2) and VP3) present in cell lysates, it was difficult to quantitate the extent, if any, of their enhancement. The maintenance of the restricted pattern of protein synthesis caused by hypertonic medium was dependent on continual peptide chain initiations. The resistance of viral protein synthesis to hypertonic conditions provides a means of detecting relatively low levels of intracellular viral protein synthesis. Analysis of the specific activity of the acid-soluble [3H]lysine pool indicated that the rate of incorporation of [3H]lysine into protein was an overestimation of the actual rate of overall protein synthesis occurring in cells exposed to hypertonic as compared to isotonic conditions. Since it is likely that both cellular and viral protein synthesis draw lysine from a single pool, this change in pool specific activity does not affect the analysis of relative rates of protein synthesis at a given level of tonicity."} {"id": "PMID:171443", "title": "Differential expression of helper viral structural polypeptides in cells transformed by clonal isolates of woolly monkey sarcoma virus.", "content": "Cell lines transformed by woolly monkey sarcoma virus (WSV) in the absence of infectious virus production were analyzed for the expression of woolly monkey helper viral p30, p12, and gp70 antigens. Several lines produced high levels of both p30 and p12, whereas gp70 was not detectable. One transformed clone expressed only p12, and in another cell line, none of the helper viral antigens were detected. The properties of each sarcoma virus bred true upon transmission, indicating that each variant represents a distinct genotype. The different cell lines were examined with respect to properties characteristic of the transformed state. The in vitro growth properties and oncogenicity of each WSV-transformed clone were indistinguishable, indicating that transformation by WSV occurs independently of the expression of at least three helper viral polypeptides.", "contents": "Differential expression of helper viral structural polypeptides in cells transformed by clonal isolates of woolly monkey sarcoma virus. Cell lines transformed by woolly monkey sarcoma virus (WSV) in the absence of infectious virus production were analyzed for the expression of woolly monkey helper viral p30, p12, and gp70 antigens. Several lines produced high levels of both p30 and p12, whereas gp70 was not detectable. One transformed clone expressed only p12, and in another cell line, none of the helper viral antigens were detected. The properties of each sarcoma virus bred true upon transmission, indicating that each variant represents a distinct genotype. The different cell lines were examined with respect to properties characteristic of the transformed state. The in vitro growth properties and oncogenicity of each WSV-transformed clone were indistinguishable, indicating that transformation by WSV occurs independently of the expression of at least three helper viral polypeptides."} {"id": "PMID:171444", "title": "Qualitative complementation test for temperature-sensitive mutants of herpes simplex virus.", "content": "A simple, rapid, qualitative method for classifying temperature-sensitive mutants of herpes simplex virus into functional complementation groups has been developed. The positive reaction observed in this test reflects the ability of mutant pairs to interact by both complementation and recombination.", "contents": "Qualitative complementation test for temperature-sensitive mutants of herpes simplex virus. A simple, rapid, qualitative method for classifying temperature-sensitive mutants of herpes simplex virus into functional complementation groups has been developed. The positive reaction observed in this test reflects the ability of mutant pairs to interact by both complementation and recombination."} {"id": "PMID:171445", "title": "Inhibition by aurintricarboxylic acid and polyethylene sulfonate of RNA transcription of vesicular stomatitis virus.", "content": "The in vitro activity of the ribonucleoprotein-dependent RNA transcriptase of vesicular stomatitis virions was found to be completely inhibited by low concentrations of aurintricarboxylic acid (ATA) and polyethylene sulfonic acid (PES) when these inhibitors were added before the start of the RNA polymerase reaction. However, if RNA synthesis was allowed to occur before ATA or PES was added, RNA synthesis continued for a short time (10 min or less) in the presence of either inhibitor at a concentration which completely inhibited uninitiated enzyme. The ability to continue to synthesize RNA in the presence of ATA or PES only developed if all four nucleoside triphosphates were present during the preincubation period prior to the addition of the inhibitors. The protection was apparently not due to the released products of RNA polymerization. The results are interpreted as indicating that ATA and PES probably inhibit some reaction other than elongation of RNA chains, and this reaction might be one involved at or near initiation sites.", "contents": "Inhibition by aurintricarboxylic acid and polyethylene sulfonate of RNA transcription of vesicular stomatitis virus. The in vitro activity of the ribonucleoprotein-dependent RNA transcriptase of vesicular stomatitis virions was found to be completely inhibited by low concentrations of aurintricarboxylic acid (ATA) and polyethylene sulfonic acid (PES) when these inhibitors were added before the start of the RNA polymerase reaction. However, if RNA synthesis was allowed to occur before ATA or PES was added, RNA synthesis continued for a short time (10 min or less) in the presence of either inhibitor at a concentration which completely inhibited uninitiated enzyme. The ability to continue to synthesize RNA in the presence of ATA or PES only developed if all four nucleoside triphosphates were present during the preincubation period prior to the addition of the inhibitors. The protection was apparently not due to the released products of RNA polymerization. The results are interpreted as indicating that ATA and PES probably inhibit some reaction other than elongation of RNA chains, and this reaction might be one involved at or near initiation sites."} {"id": "PMID:171446", "title": "Altered DNA synthesis in a mutant of Salmonella typhimurium that channels bacteriophage P22 toward lysogeny.", "content": "Pox-1, a mutant of Salmonella typhimurium, strongly channels P22 toward lysogeny. Viral DNA synthesis in this slow-growing mutant is delayed to a greater extent than viral protein synthesis. The relative enhancement of c2 repressor synthesis results in much higher repressor/DNA synthesis ratios in Pox-1 than in wild-type cells. This probably accounts for the high frequency of lysogenization.", "contents": "Altered DNA synthesis in a mutant of Salmonella typhimurium that channels bacteriophage P22 toward lysogeny. Pox-1, a mutant of Salmonella typhimurium, strongly channels P22 toward lysogeny. Viral DNA synthesis in this slow-growing mutant is delayed to a greater extent than viral protein synthesis. The relative enhancement of c2 repressor synthesis results in much higher repressor/DNA synthesis ratios in Pox-1 than in wild-type cells. This probably accounts for the high frequency of lysogenization."} {"id": "PMID:171447", "title": "Structure of B77 sarcoma virus RNA: stabilization of RNA after packaging.", "content": "Extracellular maturation of Bratislava 77(B77) sarcoma virus RNA involves a stabilization of linkage between 35S subunits since the Tm of 60 to 70S RNA in the presence of 0.5 M NaCl increases from 56 to 67.5 C as the age of the virus increases. This stabilization process is strongly temperature dependent; the rate at 45 C is increased fourfold over the rate at 37 C. As a result of the instability of the immature RNA, denaturation to subunits occurs at room temperature during phenol extraction. This dissociation can be prevented by increasing the NaCl concentration during the extraction. The data support a model which proposes that RNA subunits of oncornaviruses exist as assembled 60 to 70S RNA even in immature virions but that the linkages between subunits are stabilized as a function of time. These linkages appear to be maintained by nucleotide base pairing rather than by protein. However, isolated RNA does not undergo stabilization, suggesting that some other component of the virion is necessary for the process to occur.", "contents": "Structure of B77 sarcoma virus RNA: stabilization of RNA after packaging. Extracellular maturation of Bratislava 77(B77) sarcoma virus RNA involves a stabilization of linkage between 35S subunits since the Tm of 60 to 70S RNA in the presence of 0.5 M NaCl increases from 56 to 67.5 C as the age of the virus increases. This stabilization process is strongly temperature dependent; the rate at 45 C is increased fourfold over the rate at 37 C. As a result of the instability of the immature RNA, denaturation to subunits occurs at room temperature during phenol extraction. This dissociation can be prevented by increasing the NaCl concentration during the extraction. The data support a model which proposes that RNA subunits of oncornaviruses exist as assembled 60 to 70S RNA even in immature virions but that the linkages between subunits are stabilized as a function of time. These linkages appear to be maintained by nucleotide base pairing rather than by protein. However, isolated RNA does not undergo stabilization, suggesting that some other component of the virion is necessary for the process to occur."} {"id": "PMID:171448", "title": "Transcription of simian virus 40. V. Regulattion of simian virus 40 gene expression.", "content": "RNA \"exhaustion type\" hybridization was used to measure the complementarity of nuclear and cytoplasmic viral RNA to the early (E) and late (L) simian virus 40 (SV40) DNA strands. This type of hybridization measures the amount of labeled RNA complementary to each of the two DNA strands, rather than the fraction of each SV40 DNA strand that is homologous to SV40 RNA. At 48 h after infection, about 5% of the nuclear newly synthesized viral RNA was complementary to the E-strand (- strand) and 95% was complementary to the L-strand (+ strand). This proportion was independent of the labeling time, indicating similar accumulation of the E- and L-RNA transcripts in the nucleus. The nuclear E- and L-viral RNA transcripts sedimented in a similar manner on sucrose gradients. Of the cytoplasmic viral RNA only about 1% was complementary to the E-strand, these molecules sedimenting at 19S, whereas 99% were complementary to the L-strand and sedimented at 19S and 16S. The abundance of E-RNA transcripts in nuclei of cells infected with serially passaged virus was about four times higher than that in nuclei of cells infected with plaque-purified virus; however, the size and proportion of the corresponding cytoplasmic E- and L-RNA transcripts was independent of the type of virus used to infect the cells. According to these results at least two control mechanisms regulate viral gene expression in productively infected cells, one operates at the trnascriptional level and the second at the post-transcriptional level.", "contents": "Transcription of simian virus 40. V. Regulattion of simian virus 40 gene expression. RNA \"exhaustion type\" hybridization was used to measure the complementarity of nuclear and cytoplasmic viral RNA to the early (E) and late (L) simian virus 40 (SV40) DNA strands. This type of hybridization measures the amount of labeled RNA complementary to each of the two DNA strands, rather than the fraction of each SV40 DNA strand that is homologous to SV40 RNA. At 48 h after infection, about 5% of the nuclear newly synthesized viral RNA was complementary to the E-strand (- strand) and 95% was complementary to the L-strand (+ strand). This proportion was independent of the labeling time, indicating similar accumulation of the E- and L-RNA transcripts in the nucleus. The nuclear E- and L-viral RNA transcripts sedimented in a similar manner on sucrose gradients. Of the cytoplasmic viral RNA only about 1% was complementary to the E-strand, these molecules sedimenting at 19S, whereas 99% were complementary to the L-strand and sedimented at 19S and 16S. The abundance of E-RNA transcripts in nuclei of cells infected with serially passaged virus was about four times higher than that in nuclei of cells infected with plaque-purified virus; however, the size and proportion of the corresponding cytoplasmic E- and L-RNA transcripts was independent of the type of virus used to infect the cells. According to these results at least two control mechanisms regulate viral gene expression in productively infected cells, one operates at the trnascriptional level and the second at the post-transcriptional level."} {"id": "PMID:171449", "title": "Host influence on the activity of genes c1 and c3 in regulating the decision between lysis and lysogency in bacteriophage P22.", "content": "A Polymyxin B-sensitive mutant of Salmonella typhimurium (Pox-1) channels all infecting wild-type P22 toward lysogenization. The efficiency of this channeling is sufficiently high that P22c+ (wild type) cannot form plaques on Pox-1; phage mutants defective in repressor synthesis (P22c1, c2, c3) or refractory toward repressor (P22vir B) can form plaques. The lytic growth of all phages which have a functional c1 gene is retarded in Pox-1; this retardation is seen even in phages which cannot make repressor. We present experiments which are consistent with the explanation that the retardation is an exaggeration of a normal regulatory event. In a wild-type host, P22 genes c1 and c3 products, host RNA polymerase, and other host factors (?) interact at a promotor site (c27) IN THE PHAGE DNA. This interaction promotes repressor synthesis and represses transcription of lytic genes. In the mutant Pox-1, a host product involved in viral DNA synthesis and transcription is altered. The altered host product results in stronger retardation of lytic gene transcription. The importance of this interaction in the decision between lysis and lysogeny is discussed. The mutant Pox-1 alters the expression or activity of another phage gene. Gene c3 product is absolutely required for lysogenization in this host, although it is not so required in wild-type S. typhimurium.", "contents": "Host influence on the activity of genes c1 and c3 in regulating the decision between lysis and lysogency in bacteriophage P22. A Polymyxin B-sensitive mutant of Salmonella typhimurium (Pox-1) channels all infecting wild-type P22 toward lysogenization. The efficiency of this channeling is sufficiently high that P22c+ (wild type) cannot form plaques on Pox-1; phage mutants defective in repressor synthesis (P22c1, c2, c3) or refractory toward repressor (P22vir B) can form plaques. The lytic growth of all phages which have a functional c1 gene is retarded in Pox-1; this retardation is seen even in phages which cannot make repressor. We present experiments which are consistent with the explanation that the retardation is an exaggeration of a normal regulatory event. In a wild-type host, P22 genes c1 and c3 products, host RNA polymerase, and other host factors (?) interact at a promotor site (c27) IN THE PHAGE DNA. This interaction promotes repressor synthesis and represses transcription of lytic genes. In the mutant Pox-1, a host product involved in viral DNA synthesis and transcription is altered. The altered host product results in stronger retardation of lytic gene transcription. The importance of this interaction in the decision between lysis and lysogeny is discussed. The mutant Pox-1 alters the expression or activity of another phage gene. Gene c3 product is absolutely required for lysogenization in this host, although it is not so required in wild-type S. typhimurium."} {"id": "PMID:171450", "title": "Biochemical and biophysical characteristics of diarrhea viruses of human and calf origin.", "content": "Polyacrylamide gel electrophoretic analysis of purified preparations of human and calf diarrhea viruses indicated eight polypeptide components, or possibly nine in the case of the calf diarrhea virus. Thermal denaturation and analytical studies of the calf diarrhea virus genome showed it to consist of 11 double-stranded segments of RNA. The placing of the human and calf diarrhea viruses together with other similar viruses into a genus separate from reovirus and orbivirus, but within the family Reoviridae, is discussed.", "contents": "Biochemical and biophysical characteristics of diarrhea viruses of human and calf origin. Polyacrylamide gel electrophoretic analysis of purified preparations of human and calf diarrhea viruses indicated eight polypeptide components, or possibly nine in the case of the calf diarrhea virus. Thermal denaturation and analytical studies of the calf diarrhea virus genome showed it to consist of 11 double-stranded segments of RNA. The placing of the human and calf diarrhea viruses together with other similar viruses into a genus separate from reovirus and orbivirus, but within the family Reoviridae, is discussed."} {"id": "PMID:171451", "title": "Simian virus 40-specific proteins in HeLa cells infected with nondefective adenovirus 2-simian virus 40 hybrid viruses.", "content": "The synthesis of simian virus 40 (SV40)-specific proteins in HeLa cells infected with the nondefective adenovirus 2 (Ad2)-SV40 hybrid viruses, Ad2+ND2, Ad2+ND3, Ad2+ND4, and Ad2+ND5, was investigated. Infected-cell proteins were labeled with radioactive amino acids late after infection, when host protein synthesis was shut off, and analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. All polypeptides normally seen in Ad2-infected cells were found in cells infected by the hybrid viruses. In addition to the Ad2-specific proteins, cells infected with Ad2+ND2 contain two SV40-specific proteins with apparent molecular weights of 42,000 and 56,000, cells infected with Ad2+ND4 contain one protein with an apparent molecular weight of 56,000, and cells infected with Ad2+ND5 contain one protein with an apparent molecular weight of 42,000. Cells infected with Ad2+ND3 do not contain detectable amounts of proteins not seen during Ad2 infection. Pulse-chase experiments demonstrate that the SV40-specific proteins induced by Ad2+ND2, Ad2+ND4, and Ad2+ND5 are metabolically unstable. These proteins are not present in purified virions. Two nonstructural Ad2-specific proteins have been demonstrated in Ad2 and hybrid virus-infected cells which have a smaller apparent molecular weight after a short pulse than after a pulse followed by a chase. The molecular weight increase during the chase may be caused by the addition of carbohydrate to a polypeptide backbone.", "contents": "Simian virus 40-specific proteins in HeLa cells infected with nondefective adenovirus 2-simian virus 40 hybrid viruses. The synthesis of simian virus 40 (SV40)-specific proteins in HeLa cells infected with the nondefective adenovirus 2 (Ad2)-SV40 hybrid viruses, Ad2+ND2, Ad2+ND3, Ad2+ND4, and Ad2+ND5, was investigated. Infected-cell proteins were labeled with radioactive amino acids late after infection, when host protein synthesis was shut off, and analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. All polypeptides normally seen in Ad2-infected cells were found in cells infected by the hybrid viruses. In addition to the Ad2-specific proteins, cells infected with Ad2+ND2 contain two SV40-specific proteins with apparent molecular weights of 42,000 and 56,000, cells infected with Ad2+ND4 contain one protein with an apparent molecular weight of 56,000, and cells infected with Ad2+ND5 contain one protein with an apparent molecular weight of 42,000. Cells infected with Ad2+ND3 do not contain detectable amounts of proteins not seen during Ad2 infection. Pulse-chase experiments demonstrate that the SV40-specific proteins induced by Ad2+ND2, Ad2+ND4, and Ad2+ND5 are metabolically unstable. These proteins are not present in purified virions. Two nonstructural Ad2-specific proteins have been demonstrated in Ad2 and hybrid virus-infected cells which have a smaller apparent molecular weight after a short pulse than after a pulse followed by a chase. The molecular weight increase during the chase may be caused by the addition of carbohydrate to a polypeptide backbone."} {"id": "PMID:171452", "title": "N-terminal amino acid sequences in the major capsid proteins of foot-and-mouth disease virus types A, O, and C.", "content": "Sequences of amino acids at the N-termini of virus proteins VP1, VP2, and VP3 were determined for foot-and-mouth disease virus types A12 strain 119, O1Brugge and C3Resende. In the polyacrylamide gel electrophoresis system used to purify the proteins, VP3 migrated faster than VP1 or VP2; and in the virion, VP3 could be cleaved by trypsin into VP3a and VP3b. The N-terminal amino acids for each of the virus types were glycine in VP1, aspartic acid in VP2, and threonine in VP3. No divergences in sequence across the virus types were indicated until at least the fourth position in VP1, and the third in VP3. For virus types A12, O1 and C3, the sequences were, respectively: for VP1 (Gly-ile-phe,pro,val---), (Gly,ile,phe---) and Gly-ile-phe,ala---); for VP2 (Asp,X,met---), (Asp---) and Asp-leu---); and for VP3 (Thr-thr-ala-thr---), (Thr-thr-ser---) and (Thr-thr---). Unresolved mixtures of VP3a and VP3b, from either A12 or O1 viruses, appeared to have the N-terminal amino acids threonine, which is presumed to be the same threonine as in uncleaved VP3 and serine, which is generated by the tryptic cleavage.", "contents": "N-terminal amino acid sequences in the major capsid proteins of foot-and-mouth disease virus types A, O, and C. Sequences of amino acids at the N-termini of virus proteins VP1, VP2, and VP3 were determined for foot-and-mouth disease virus types A12 strain 119, O1Brugge and C3Resende. In the polyacrylamide gel electrophoresis system used to purify the proteins, VP3 migrated faster than VP1 or VP2; and in the virion, VP3 could be cleaved by trypsin into VP3a and VP3b. The N-terminal amino acids for each of the virus types were glycine in VP1, aspartic acid in VP2, and threonine in VP3. No divergences in sequence across the virus types were indicated until at least the fourth position in VP1, and the third in VP3. For virus types A12, O1 and C3, the sequences were, respectively: for VP1 (Gly-ile-phe,pro,val---), (Gly,ile,phe---) and Gly-ile-phe,ala---); for VP2 (Asp,X,met---), (Asp---) and Asp-leu---); and for VP3 (Thr-thr-ala-thr---), (Thr-thr-ser---) and (Thr-thr---). Unresolved mixtures of VP3a and VP3b, from either A12 or O1 viruses, appeared to have the N-terminal amino acids threonine, which is presumed to be the same threonine as in uncleaved VP3 and serine, which is generated by the tryptic cleavage."} {"id": "PMID:171453", "title": "Properties and origins of infectious rhinovirus type 14 particles of different buoyant densities.", "content": "Isopycnic centrifugation of rhinovirus type 14 (RV14), purified from infected HeLa or KB cell cultures, into CsCl gradients resolved two bands of infectious virus particles with buoyant density values of 1.409 +/- 0.007 (H virus) and 1.386 +/- 0.004 (L virus) g/ml. Only H virus was detected by incorporation of radiolabeled uridine into viral RNA, and H virus accounted for the majority of infectivity in gradients. H and L virus could not be differentiated by plaque morphology, extent of neutralization by RV14-specific antiserum, or particle size. Electron microscope studies showed that most L-virus particles were associated with an amorphous material. Treatment of L virus with proteolytic enzymes or rebanding L virus in CsCl gradients resulted in recovery of the majority of infectivity as H virus. Virus purified from cell-free fluids from infected HeLa or KB cell cultures banded only as H virus. HeLa cell cultures challenged with purified H virus and harvested at 3 h postinoculation for virus purification yielded only infectious H virus. Both H and L viruses were detected in cell cultures that had been challenged with purified H virus and harvested at 12 h postinoculation. The data suggest that H virus represents progeny virus, whereas L virus represents sequestered infectious virus particles which become associated with an amorphous material and do not enter into viral replicative processes.", "contents": "Properties and origins of infectious rhinovirus type 14 particles of different buoyant densities. Isopycnic centrifugation of rhinovirus type 14 (RV14), purified from infected HeLa or KB cell cultures, into CsCl gradients resolved two bands of infectious virus particles with buoyant density values of 1.409 +/- 0.007 (H virus) and 1.386 +/- 0.004 (L virus) g/ml. Only H virus was detected by incorporation of radiolabeled uridine into viral RNA, and H virus accounted for the majority of infectivity in gradients. H and L virus could not be differentiated by plaque morphology, extent of neutralization by RV14-specific antiserum, or particle size. Electron microscope studies showed that most L-virus particles were associated with an amorphous material. Treatment of L virus with proteolytic enzymes or rebanding L virus in CsCl gradients resulted in recovery of the majority of infectivity as H virus. Virus purified from cell-free fluids from infected HeLa or KB cell cultures banded only as H virus. HeLa cell cultures challenged with purified H virus and harvested at 3 h postinoculation for virus purification yielded only infectious H virus. Both H and L viruses were detected in cell cultures that had been challenged with purified H virus and harvested at 12 h postinoculation. The data suggest that H virus represents progeny virus, whereas L virus represents sequestered infectious virus particles which become associated with an amorphous material and do not enter into viral replicative processes."} {"id": "PMID:171454", "title": "Proteins specified by herpes simplex virus. XIII. Glycosylation of viral polypeptides.", "content": "In the course of herpes simplex virus 1 (HSV-1) replication in human epidermoid carcinoma no. 2 cells, the synthesis and glycosylation of host cell proteins ceases and is replaced by the synthesis and glycosylation of virus-specified polypeptides. Analyses of the synthesis of viral glycoproteins show that the glycosylation of viral polypeptides occurs late in the virus growth cycle and that certain of the precursors to major vital glycoproteins are members of the gamma group of polypeptides, i.e., polypeptides synthesized at increasing rates until 12 to 15 h postinfection. Viral glycoproteins are formed by stepwise additions of heterosaccharide chains to completed precursor polypeptides. The precursor and the highly glycosylated product are separable by gel electrophoresis and are localized in different fractions of infected cells. Within 15 min of their synthesis, precursor polypeptides acquire heterosaccharide chains of about 2,000 molecular weight, which contain glucosamine but little or nor fucose or sialic acid. Both precursor and product of this first stage of glycosylation are absent or present in low concentrations in the surface membranes of the infected cell and in the virion. The partially glycosylated product is then conjugated further in a slow, discontinuous process to form the mature glycoprotein of the virion and plasma membrane. These mature products bear large heterosaccharide units with molecular weights greater than 4,000 to 5,000; these contain fucose and sialic acid as well as glucosamine. Heterosaccharide chains from infected and uninfected cells are distributed among discrete size classes and the smallest chains consist of multiple saccharide residues.", "contents": "Proteins specified by herpes simplex virus. XIII. Glycosylation of viral polypeptides. In the course of herpes simplex virus 1 (HSV-1) replication in human epidermoid carcinoma no. 2 cells, the synthesis and glycosylation of host cell proteins ceases and is replaced by the synthesis and glycosylation of virus-specified polypeptides. Analyses of the synthesis of viral glycoproteins show that the glycosylation of viral polypeptides occurs late in the virus growth cycle and that certain of the precursors to major vital glycoproteins are members of the gamma group of polypeptides, i.e., polypeptides synthesized at increasing rates until 12 to 15 h postinfection. Viral glycoproteins are formed by stepwise additions of heterosaccharide chains to completed precursor polypeptides. The precursor and the highly glycosylated product are separable by gel electrophoresis and are localized in different fractions of infected cells. Within 15 min of their synthesis, precursor polypeptides acquire heterosaccharide chains of about 2,000 molecular weight, which contain glucosamine but little or nor fucose or sialic acid. Both precursor and product of this first stage of glycosylation are absent or present in low concentrations in the surface membranes of the infected cell and in the virion. The partially glycosylated product is then conjugated further in a slow, discontinuous process to form the mature glycoprotein of the virion and plasma membrane. These mature products bear large heterosaccharide units with molecular weights greater than 4,000 to 5,000; these contain fucose and sialic acid as well as glucosamine. Heterosaccharide chains from infected and uninfected cells are distributed among discrete size classes and the smallest chains consist of multiple saccharide residues."} {"id": "PMID:171455", "title": "Comparison of the virion proteins specified by herpes simplex virus types 1 and 2.", "content": "Purified herpes simplex virus type 2 (HSV-2) virions were found to contain approximately the same number of polypeptides as HSV type 1 (HSV-1) virions. Comparisons of the structural proteins specified by five independent HSV-2 isolates revealed some minor differences in their electrophoretic profiles on sodium dodecyl sulfate-acrylamide gels; certain invariant features of the electrophoretic profiles, however, allowed clear differentiation between all the HSV-2 isolates and HSV-1.", "contents": "Comparison of the virion proteins specified by herpes simplex virus types 1 and 2. Purified herpes simplex virus type 2 (HSV-2) virions were found to contain approximately the same number of polypeptides as HSV type 1 (HSV-1) virions. Comparisons of the structural proteins specified by five independent HSV-2 isolates revealed some minor differences in their electrophoretic profiles on sodium dodecyl sulfate-acrylamide gels; certain invariant features of the electrophoretic profiles, however, allowed clear differentiation between all the HSV-2 isolates and HSV-1."} {"id": "PMID:171456", "title": "Method of examining viral RNA metabolism in cells in culture: metabolism of vesicular stomatitis virus RNA.", "content": "A method is described for radioactively labeling viral RNA and then quickly halting further incorporation of radioactive precursor into RNA so that the fate of the labeled RNA can be followed. Small complementary RNAs synthesized during vesicular stomatitis virus infection in the presence of cycloheximide do not metabolize to virion length molecules when protein synthesis inhibition is reversed.", "contents": "Method of examining viral RNA metabolism in cells in culture: metabolism of vesicular stomatitis virus RNA. A method is described for radioactively labeling viral RNA and then quickly halting further incorporation of radioactive precursor into RNA so that the fate of the labeled RNA can be followed. Small complementary RNAs synthesized during vesicular stomatitis virus infection in the presence of cycloheximide do not metabolize to virion length molecules when protein synthesis inhibition is reversed."} {"id": "PMID:171457", "title": "Amounts of Epstein-Barr virus DNA in somatic cell hybrids between burkitt lymphoma-derived cell lines.", "content": "The amounts of Epstein-Barr virus DNA in somatic cell hybrids between human lymphoid cell lines were found to be higher than in the parental cell lines, although the hybrids were not induced to spontaneous virus production.", "contents": "Amounts of Epstein-Barr virus DNA in somatic cell hybrids between burkitt lymphoma-derived cell lines. The amounts of Epstein-Barr virus DNA in somatic cell hybrids between human lymphoid cell lines were found to be higher than in the parental cell lines, although the hybrids were not induced to spontaneous virus production."} {"id": "PMID:171458", "title": "Should patients with zoster receive zoster immune globulin?", "content": "Zoster developed in 55 patients, and 15, generalized disease occurred. Twelve of 14 patients with dissemination had prompt appearance of both complement-fixing (CF) antibody and fluorescent antibody against varicella-zoster (VS) membrane antigen (FAMA). The geometric mean titers of VZ antibody from the first to the fifth and the sixth through the tenth days following onset of zoster were similar in patients with localized and generalized involvement. Two patients with disseminated zoster had undetectable CF antibody, but VZ FAMA was demonstrable. Because the clinical course of zoster appears to be unrelated to the serologic response to VZ virus, it is unlikely that administration of antibody with zoster would be benefit in this disease.", "contents": "Should patients with zoster receive zoster immune globulin? Zoster developed in 55 patients, and 15, generalized disease occurred. Twelve of 14 patients with dissemination had prompt appearance of both complement-fixing (CF) antibody and fluorescent antibody against varicella-zoster (VS) membrane antigen (FAMA). The geometric mean titers of VZ antibody from the first to the fifth and the sixth through the tenth days following onset of zoster were similar in patients with localized and generalized involvement. Two patients with disseminated zoster had undetectable CF antibody, but VZ FAMA was demonstrable. Because the clinical course of zoster appears to be unrelated to the serologic response to VZ virus, it is unlikely that administration of antibody with zoster would be benefit in this disease."} {"id": "PMID:171460", "title": "The respiratory effects of chloromethyl methyl ether.", "content": "A prospective study of 125 chemical workers was carried out for ten years to investigate the incidence of lung cancer. Some of the men were exposed to chloromethyl methyl ether containing bis(chloromethyl) ether as an impurity. Bronchogenic carcinoma was markedly increased among them, with a strong dose-response relationship. An unexpected inverse relationship was noted between smoking and the incidence of lung cancer. The neoplasms (all small-cell carcinomas) occurred in relatively young men. Symptoms of chronic bronchitis were reported more often among men exposed to chloromethyl ether, and a dose-response relationship was apparent, with smoking a cofactor. Ventilatory function was not significantly affected by chemical exposure. Periodic screening over the first five years of the study showed a decrease in chronic coughing and an increase in dyspnea while chemical exposure was diminishing.", "contents": "The respiratory effects of chloromethyl methyl ether. A prospective study of 125 chemical workers was carried out for ten years to investigate the incidence of lung cancer. Some of the men were exposed to chloromethyl methyl ether containing bis(chloromethyl) ether as an impurity. Bronchogenic carcinoma was markedly increased among them, with a strong dose-response relationship. An unexpected inverse relationship was noted between smoking and the incidence of lung cancer. The neoplasms (all small-cell carcinomas) occurred in relatively young men. Symptoms of chronic bronchitis were reported more often among men exposed to chloromethyl ether, and a dose-response relationship was apparent, with smoking a cofactor. Ventilatory function was not significantly affected by chemical exposure. Periodic screening over the first five years of the study showed a decrease in chronic coughing and an increase in dyspnea while chemical exposure was diminishing."} {"id": "PMID:171462", "title": "Adenoid cystic carcinoma (cylindroma) of the trachea masquerading as asthma.", "content": "A 40-year-old woman was admitted with upper airway obstruction; chest roentgenogram with tomograms, laryngoscopy, and bronchoscopy verified the presence of a subglottic tumor. Spirometry disclosed a maximum inspiratory flow rate more reduced than in the maximum expiratory flow rate, suggestive of upper airway obstruction. The pathologic conditions were consistent with cystic adenoid carcinoma (cylindroma) of the trachea. The patient underwent tracheostomy and total laryngectomy with an uneventful recovery. No evidence of local extension or distant metastases were evident at time of surgery.", "contents": "Adenoid cystic carcinoma (cylindroma) of the trachea masquerading as asthma. A 40-year-old woman was admitted with upper airway obstruction; chest roentgenogram with tomograms, laryngoscopy, and bronchoscopy verified the presence of a subglottic tumor. Spirometry disclosed a maximum inspiratory flow rate more reduced than in the maximum expiratory flow rate, suggestive of upper airway obstruction. The pathologic conditions were consistent with cystic adenoid carcinoma (cylindroma) of the trachea. The patient underwent tracheostomy and total laryngectomy with an uneventful recovery. No evidence of local extension or distant metastases were evident at time of surgery."} {"id": "PMID:171463", "title": "Cortisol secretion in Nelson syndrome: Persistence after \"total\" adrenalectomy for Cushing syndrome.", "content": "In two patients who were severely pigmented (Nelson syndrome) following bilateral adrenalectomy for Cushing syndrome, symptoms of hyper-cortisolism developed while they were receiving only physiologic steroid replacement. Cortical assays proved that endogenous cortisol production had not been obliterated. Even after total adrenalectomy, steroid measurement should be performed to guard against adrenocortical excess.", "contents": "Cortisol secretion in Nelson syndrome: Persistence after \"total\" adrenalectomy for Cushing syndrome. In two patients who were severely pigmented (Nelson syndrome) following bilateral adrenalectomy for Cushing syndrome, symptoms of hyper-cortisolism developed while they were receiving only physiologic steroid replacement. Cortical assays proved that endogenous cortisol production had not been obliterated. Even after total adrenalectomy, steroid measurement should be performed to guard against adrenocortical excess."} {"id": "PMID:171464", "title": "Interaction in culture between mouse ascites hepatoma (MH-134) cells and lymphoid cells of isologous mice.", "content": "Thymocytes or lymphocytes of mesenteric lymph nodes were obtained from mice bearing subcutaneously mouse ascites hepatoma MH-134 for 5 to 40 days. These lymphoid cells were added into the cultures of MH-134 cells. Morphological changes of cells in the mixed cultures were observed by time-lapse cinemicrography for the period of 4 weeks. Lymphoid cells were phagocytosed by MH-134 cells, and, in most cases, the tumor cells did not undergo any damage due to the phagocytosis. The exceptional cases were as follows: When MH-134 cells were mixed with thymocytes from mice bearing MH-134 tumor for 5 days, MH-134 cells phagocytosed thymocytes but some of them died later. In the mixed cultures of MH-134 cells and thymocytes or mesenteric lymph node lymphocytes from mice bearing MH-134 for 14 or 15 days, MH-134 cells phagocytosed lymphoid cells but died later by the burst of cytoplasm. By the burst many lymphoid cells phagocytosed appeared from the broken cytoplasm of MH-134 cells and, in some cases, the lymphoid cells looked to be alive. These findings suggest the possibility that lymphoid cells attack tumor cells not only from the cell surface but also from the inside being phagocytosed by tumor cells.", "contents": "Interaction in culture between mouse ascites hepatoma (MH-134) cells and lymphoid cells of isologous mice. Thymocytes or lymphocytes of mesenteric lymph nodes were obtained from mice bearing subcutaneously mouse ascites hepatoma MH-134 for 5 to 40 days. These lymphoid cells were added into the cultures of MH-134 cells. Morphological changes of cells in the mixed cultures were observed by time-lapse cinemicrography for the period of 4 weeks. Lymphoid cells were phagocytosed by MH-134 cells, and, in most cases, the tumor cells did not undergo any damage due to the phagocytosis. The exceptional cases were as follows: When MH-134 cells were mixed with thymocytes from mice bearing MH-134 tumor for 5 days, MH-134 cells phagocytosed thymocytes but some of them died later. In the mixed cultures of MH-134 cells and thymocytes or mesenteric lymph node lymphocytes from mice bearing MH-134 for 14 or 15 days, MH-134 cells phagocytosed lymphoid cells but died later by the burst of cytoplasm. By the burst many lymphoid cells phagocytosed appeared from the broken cytoplasm of MH-134 cells and, in some cases, the lymphoid cells looked to be alive. These findings suggest the possibility that lymphoid cells attack tumor cells not only from the cell surface but also from the inside being phagocytosed by tumor cells."} {"id": "PMID:171465", "title": "Pathogenicity of mouse hepatitis virus for mice depending upon host age and route of infection.", "content": "Day-old to 4-week-old mice from a breeder colony which had been seromonitored to be free from mouse hepatitis virus infection, were tested for susceptibility to the virus by different routes of inoculation. After intraperitoneal, intravenous and intracerebral inoculation of 10(2) or more plaque-forming units of the virus, mice of all ages died of acute hepatitis. While day-old mice died also after subcutaneous, intranasal and peroral routes of inoculation, those 3 weeks or more of age resisted to infection by these routes. To intranasal inoculation mice 1 and 2 weeks of age were fully susceptible but some of the resisted to peroral inoculation. In the course of non-fatal infection in 4-week-old mice after intranasal inoculation, viremia and production of some hepatic lesions were recognized and infection became fatal in association with cortisone treatment. The results suggested that the intranasal route of infection may be of importance for spreading of infection in mouse breeding colonies in which inapparent infection is prevailing.", "contents": "Pathogenicity of mouse hepatitis virus for mice depending upon host age and route of infection. Day-old to 4-week-old mice from a breeder colony which had been seromonitored to be free from mouse hepatitis virus infection, were tested for susceptibility to the virus by different routes of inoculation. After intraperitoneal, intravenous and intracerebral inoculation of 10(2) or more plaque-forming units of the virus, mice of all ages died of acute hepatitis. While day-old mice died also after subcutaneous, intranasal and peroral routes of inoculation, those 3 weeks or more of age resisted to infection by these routes. To intranasal inoculation mice 1 and 2 weeks of age were fully susceptible but some of the resisted to peroral inoculation. In the course of non-fatal infection in 4-week-old mice after intranasal inoculation, viremia and production of some hepatic lesions were recognized and infection became fatal in association with cortisone treatment. The results suggested that the intranasal route of infection may be of importance for spreading of infection in mouse breeding colonies in which inapparent infection is prevailing."} {"id": "PMID:171466", "title": "Carcinogenesis in tissue culture 24: tumorigenicity and aggregate-forming capacity of mammalian cells in culture.", "content": "Twenty two kinds of strains and substrains of mammalian cells were cultivated on a gyratory shaker to obtain cell aggregates. The relationship between the morphology of aggregates and tumorigenicity of the cells was investigated. In some groups of cells, the size of aggregates corresponded with their tumorigenicity, e.g. among rat liver cells untreated, hepatoma cells produced by back-transplantation of rat liver cells after the treatment with a chemical carcinogen in tissue culture, and the hepatoma cells passaged serially through rats. The correspondence, however, was generalized to not all the cell strains. It was impossible to identify the tumorigenicity of cells by their aggregate-forming capacity.", "contents": "Carcinogenesis in tissue culture 24: tumorigenicity and aggregate-forming capacity of mammalian cells in culture. Twenty two kinds of strains and substrains of mammalian cells were cultivated on a gyratory shaker to obtain cell aggregates. The relationship between the morphology of aggregates and tumorigenicity of the cells was investigated. In some groups of cells, the size of aggregates corresponded with their tumorigenicity, e.g. among rat liver cells untreated, hepatoma cells produced by back-transplantation of rat liver cells after the treatment with a chemical carcinogen in tissue culture, and the hepatoma cells passaged serially through rats. The correspondence, however, was generalized to not all the cell strains. It was impossible to identify the tumorigenicity of cells by their aggregate-forming capacity."} {"id": "PMID:171467", "title": "Sex difference in the development of fatty liver by orotic acid.", "content": "Effects of orotic acid on liver lipid accumulation and incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein, and into serum beta-lipoprotein were studied. Male and female rats of Wistar strain were fed a semisynthetic diet supplemented with 1 per cent orotic acid for 7 days. Feeding of orotic acid induced a marked fatty liver in female rats, but not in males. In female rats, radioactivity in liver phosphatidylcholine was significantly decreased by orotic acid, and that in liver protein was slightly decreased. In male rats, incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein was unchanged between the control and the rats fed orotic acid. Radioactivity in serum beta-lipoprotein was decreased to a greater extent in female rats than in males. These results suggest that sex difference in the development of fatty liver may be due to the difference in the effect of orotic acid on liver phosphatidylcholine biosynthesis.", "contents": "Sex difference in the development of fatty liver by orotic acid. Effects of orotic acid on liver lipid accumulation and incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein, and into serum beta-lipoprotein were studied. Male and female rats of Wistar strain were fed a semisynthetic diet supplemented with 1 per cent orotic acid for 7 days. Feeding of orotic acid induced a marked fatty liver in female rats, but not in males. In female rats, radioactivity in liver phosphatidylcholine was significantly decreased by orotic acid, and that in liver protein was slightly decreased. In male rats, incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein was unchanged between the control and the rats fed orotic acid. Radioactivity in serum beta-lipoprotein was decreased to a greater extent in female rats than in males. These results suggest that sex difference in the development of fatty liver may be due to the difference in the effect of orotic acid on liver phosphatidylcholine biosynthesis."} {"id": "PMID:171470", "title": "[Familial glucocorticoid insufficiency (author's transl)].", "content": "Familial glucocortivoid insufficiency--also called hereditary lack of response of the adrenals to ACTH-has not yet been described in Europe. Isolated glucocorticoid insufficiency combined with intact secretion of aldosterone and high plasma level of ACTH are characteristic. The diagnostic difficulties are demonstrated by the deaths before diagnosis of 13 siblings of 21 patients from 9 families. One such family is described. The first of 3 children died at the age of 3-1/2 years after a two day illness interpreted as encephalitis. Another boy, aged 4-1/2 years, had a hypoglycemic attack. 3 months later he died in status epilepticus after a short feverish illness. At autopsy the adrenals were very small. Histologically only the glomerulous zone was developed. An the hypophysis there was hyperplasia of the R cells producing ACTH. The 6 year old sister had been pronouncedly pigmented from the age of a few months onwards. Age in terms of height and bone development corresponded to 8-1/2 and 7-1/2 years. After intravenous insulin and synacthen plasmacorticoids could not be found. With normal and low supply of salt, the following data were found: Renin-activity 2.9 and 5.6 ng/ml p.h. respectively; rate of aldosterone secretion 62.6 and 151.5 mug/24 hrs.; average aldosterone plasma concentration 9.39 and 27.7 ng/100 ml respectively; MCR 666 and 5471 p/24 hrs. Plasma ACTH in this patient (5086--7200 pg/ml) and, post mortem, in her brother (8100 pg/ml), were extremely reaised.", "contents": "[Familial glucocorticoid insufficiency (author's transl)]. Familial glucocortivoid insufficiency--also called hereditary lack of response of the adrenals to ACTH-has not yet been described in Europe. Isolated glucocorticoid insufficiency combined with intact secretion of aldosterone and high plasma level of ACTH are characteristic. The diagnostic difficulties are demonstrated by the deaths before diagnosis of 13 siblings of 21 patients from 9 families. One such family is described. The first of 3 children died at the age of 3-1/2 years after a two day illness interpreted as encephalitis. Another boy, aged 4-1/2 years, had a hypoglycemic attack. 3 months later he died in status epilepticus after a short feverish illness. At autopsy the adrenals were very small. Histologically only the glomerulous zone was developed. An the hypophysis there was hyperplasia of the R cells producing ACTH. The 6 year old sister had been pronouncedly pigmented from the age of a few months onwards. Age in terms of height and bone development corresponded to 8-1/2 and 7-1/2 years. After intravenous insulin and synacthen plasmacorticoids could not be found. With normal and low supply of salt, the following data were found: Renin-activity 2.9 and 5.6 ng/ml p.h. respectively; rate of aldosterone secretion 62.6 and 151.5 mug/24 hrs.; average aldosterone plasma concentration 9.39 and 27.7 ng/100 ml respectively; MCR 666 and 5471 p/24 hrs. Plasma ACTH in this patient (5086--7200 pg/ml) and, post mortem, in her brother (8100 pg/ml), were extremely reaised."} {"id": "PMID:171471", "title": "[Results of catamnestic, neurological and psychological investigations in children suffering from cytomegaly virus infection, diagnosed in neonates (author's transl)].", "content": "Report on results of follow-up in 10 children, in 9 of whom clinical findings at the age between 6 and 11 months suggested the diagnosis of connatal cytomegaly. All 10 children secreted cytomegaly virus in the urine. In 3 of them post-natal infection appears probable. Follow-up was carried out at the ages between 3 and 5.9 years. Physical development was delayed in 4, severe neurologic damage occurred in 2, medium severe or minimal, in part reversible, neurologic signs in 3 childrens. The 2 most severely neurologically damaged children could not be examined psychologically. The IQ of the other 8 was between 92 and 105. 3 children showed in individual other tests only minor, insignificant loss of performance, 2 more pronounced defects which suggested cerebral damage.", "contents": "[Results of catamnestic, neurological and psychological investigations in children suffering from cytomegaly virus infection, diagnosed in neonates (author's transl)]. Report on results of follow-up in 10 children, in 9 of whom clinical findings at the age between 6 and 11 months suggested the diagnosis of connatal cytomegaly. All 10 children secreted cytomegaly virus in the urine. In 3 of them post-natal infection appears probable. Follow-up was carried out at the ages between 3 and 5.9 years. Physical development was delayed in 4, severe neurologic damage occurred in 2, medium severe or minimal, in part reversible, neurologic signs in 3 childrens. The 2 most severely neurologically damaged children could not be examined psychologically. The IQ of the other 8 was between 92 and 105. 3 children showed in individual other tests only minor, insignificant loss of performance, 2 more pronounced defects which suggested cerebral damage."} {"id": "PMID:171472", "title": "[Investigation of cyclic renal adenosinmonophosphate (yamp)-excretion in pseudohypoparathyreoidism (author's transl)].", "content": "Report on a boy aged 6-1/2 years with pseudohypoparathyroidism. This is due to a genetic lack of PTH inducible adenocyclase. Even during vitamin D treatment renal camp formation by giving PTH extract cannot be stimulated, while in this situation. PTH shows a clearly phosphaturic effect. Whether this is due to a PTH potentiated vitamin D effect is discussed. The assay of camp in urine before and after stimulation with PTH extract has proved the most certain diagnostic criterion.", "contents": "[Investigation of cyclic renal adenosinmonophosphate (yamp)-excretion in pseudohypoparathyreoidism (author's transl)]. Report on a boy aged 6-1/2 years with pseudohypoparathyroidism. This is due to a genetic lack of PTH inducible adenocyclase. Even during vitamin D treatment renal camp formation by giving PTH extract cannot be stimulated, while in this situation. PTH shows a clearly phosphaturic effect. Whether this is due to a PTH potentiated vitamin D effect is discussed. The assay of camp in urine before and after stimulation with PTH extract has proved the most certain diagnostic criterion."} {"id": "PMID:171473", "title": "[Ultrasound in the differential diagnosis of Wilms tumors (author's transl)].", "content": "The usefulness of ultrasound for distinguishing between Wilms tumor and hydronephrosis is shown in a case where radiographic signs were not clear. Ultrasound always permits differentiation between cystic and solid tumors.", "contents": "[Ultrasound in the differential diagnosis of Wilms tumors (author's transl)]. The usefulness of ultrasound for distinguishing between Wilms tumor and hydronephrosis is shown in a case where radiographic signs were not clear. Ultrasound always permits differentiation between cystic and solid tumors."} {"id": "PMID:171474", "title": "[Plasma ACTH and Nelson tumors in bilaterally adrenalectomized Cushing patients].", "content": "Bilaterally adrenalectomized patients (18) because of Cushing's syndrome were studied. 16 of these 18 persons exhibited fairly high plasma ACTH levels. Distinctly elevated plasma ACTH levels were observed in 6 of them. 5 patients of this group showed an enlarged sella and deep pigmentation of the skin. 4 of the latter group had a mucoid cell adenoma which was removed selectively. After the surgery the ACTH values were found to be within normal range without any significant endocrine dysfunction of the pituitary. A long-term ACTH survey revealed that the ACTH levels remained within the ranges of bilaterally adrenalectomized Cushing patients without concomitant enlargement of the sella or pigmentation.", "contents": "[Plasma ACTH and Nelson tumors in bilaterally adrenalectomized Cushing patients]. Bilaterally adrenalectomized patients (18) because of Cushing's syndrome were studied. 16 of these 18 persons exhibited fairly high plasma ACTH levels. Distinctly elevated plasma ACTH levels were observed in 6 of them. 5 patients of this group showed an enlarged sella and deep pigmentation of the skin. 4 of the latter group had a mucoid cell adenoma which was removed selectively. After the surgery the ACTH values were found to be within normal range without any significant endocrine dysfunction of the pituitary. A long-term ACTH survey revealed that the ACTH levels remained within the ranges of bilaterally adrenalectomized Cushing patients without concomitant enlargement of the sella or pigmentation."} {"id": "PMID:171477", "title": "Paracrystalloids from mitochondria in thyroid follicular cells. Normal occurrence and experimental induction.", "content": "The ultrastructure of the follicular cells of the thyroid gland of bats caught in early June, when the euthyroid state is being restored following the phase of great thyroid activity that occurs at arousal, was studied. Several ultrastructural features were found which had not been observed in animals caught at other periods of the annual life cycle. The most striking ultrastructural feature was the presence in many cells of prominent, large membrane-enclosed paracrystalloid bodies. The paracrystalloids exceeded 6.0 mum in length and were approximately 1.0 mum. in width. Examination of transition forms showed that paracrystalloids were derived from mitochondria and were formed by the reorganization of the cristae into parallel closely apposed membranes. The membranes run longitudinally in loops from one end of the mitochondrion to the other. Similar mitochondrial alterations were observed in rats by duplicating the thyroid conditions of the June bat. Rats were given thiouracil for 10 weeks followed by L-triiodothyronine injection. These animals all showed similar mitochondrial-paracrystalline alterations which were not seen in hypophysectomized animals or animals given L-triiodothyronine alone. Mitochondria from thyroids of rats given thiouracil alone showed an increase in size and number and changes in shape and internal structure. The results of the bat and rat studies suggest that rapid shutdown of active follicular cells appears to promote thyroid paracrystalloid formation from mitochondria.", "contents": "Paracrystalloids from mitochondria in thyroid follicular cells. Normal occurrence and experimental induction. The ultrastructure of the follicular cells of the thyroid gland of bats caught in early June, when the euthyroid state is being restored following the phase of great thyroid activity that occurs at arousal, was studied. Several ultrastructural features were found which had not been observed in animals caught at other periods of the annual life cycle. The most striking ultrastructural feature was the presence in many cells of prominent, large membrane-enclosed paracrystalloid bodies. The paracrystalloids exceeded 6.0 mum in length and were approximately 1.0 mum. in width. Examination of transition forms showed that paracrystalloids were derived from mitochondria and were formed by the reorganization of the cristae into parallel closely apposed membranes. The membranes run longitudinally in loops from one end of the mitochondrion to the other. Similar mitochondrial alterations were observed in rats by duplicating the thyroid conditions of the June bat. Rats were given thiouracil for 10 weeks followed by L-triiodothyronine injection. These animals all showed similar mitochondrial-paracrystalline alterations which were not seen in hypophysectomized animals or animals given L-triiodothyronine alone. Mitochondria from thyroids of rats given thiouracil alone showed an increase in size and number and changes in shape and internal structure. The results of the bat and rat studies suggest that rapid shutdown of active follicular cells appears to promote thyroid paracrystalloid formation from mitochondria."} {"id": "PMID:171478", "title": "Virus-induced abortion. Studies of equine herpesvirus 1 (abortion virus) in hamsters.", "content": "A hamster-adapted strain of equine herpesvirus-1 (equine abortion virus) caused severe hepatic degeneration in both pregnant and nonpregnant hamsters and, in addition, regularly induced abortion in pregnant hamsters inoculated at midgestation. In nonpregnant hamsters, the only consistently affected organ was the liver despite a prolonged viremia. Newborn animals usually died 1 to 2 days after inoculation; adults died 5 to 9 days after inoculation. In pregnant hamsters, the virus had a tropism for the placenta as well as the liver. The placental infection was confined almost exclusively to one cell type in the fetal portion of the placenta: the trophoblast cells of the syncytiotrophoblast zone. Necrosis of this zone led to fetal death and abortion. Infection of the fetus did not occur.", "contents": "Virus-induced abortion. Studies of equine herpesvirus 1 (abortion virus) in hamsters. A hamster-adapted strain of equine herpesvirus-1 (equine abortion virus) caused severe hepatic degeneration in both pregnant and nonpregnant hamsters and, in addition, regularly induced abortion in pregnant hamsters inoculated at midgestation. In nonpregnant hamsters, the only consistently affected organ was the liver despite a prolonged viremia. Newborn animals usually died 1 to 2 days after inoculation; adults died 5 to 9 days after inoculation. In pregnant hamsters, the virus had a tropism for the placenta as well as the liver. The placental infection was confined almost exclusively to one cell type in the fetal portion of the placenta: the trophoblast cells of the syncytiotrophoblast zone. Necrosis of this zone led to fetal death and abortion. Infection of the fetus did not occur."} {"id": "PMID:171479", "title": "Oligodendrocytes and their myelin-plasma membrane connections in JHM mouse hepatitis virus encephalomyelitis.", "content": "Mice infected with JHM strain of mouse hepatitis virus develop a demyelinating encephalomyelitis. Myelin sheaths are stripped off axons by invading macrophages after degeneration of the infected oligodendrocytes. The derivation of the virus from granular cytoplasmic particles that condense around and bud into endoplasmic reticulum is demonstrated. The infected oligodendrocytes undergo hypertrophic changes prior to degeneration. Hypertrophic cells are characterized by abundant microtubules, filaments, mitochondria, aggregates of electron-dense particles, and numerous, unusual plasma membrane connections to myelin lamellae. Vacular and hydropic changes are prominent in degenerating cells. The significance of finding infected oligodendrocytes with altered myelin-plasma membrane connections is discussed with reference to the pathogenesis of recurrent, postinfectious demyelination known to develop subsequent to acute virus infections.", "contents": "Oligodendrocytes and their myelin-plasma membrane connections in JHM mouse hepatitis virus encephalomyelitis. Mice infected with JHM strain of mouse hepatitis virus develop a demyelinating encephalomyelitis. Myelin sheaths are stripped off axons by invading macrophages after degeneration of the infected oligodendrocytes. The derivation of the virus from granular cytoplasmic particles that condense around and bud into endoplasmic reticulum is demonstrated. The infected oligodendrocytes undergo hypertrophic changes prior to degeneration. Hypertrophic cells are characterized by abundant microtubules, filaments, mitochondria, aggregates of electron-dense particles, and numerous, unusual plasma membrane connections to myelin lamellae. Vacular and hydropic changes are prominent in degenerating cells. The significance of finding infected oligodendrocytes with altered myelin-plasma membrane connections is discussed with reference to the pathogenesis of recurrent, postinfectious demyelination known to develop subsequent to acute virus infections."} {"id": "PMID:171520", "title": "Studies of the oligomycin-sensitive ATPase from yeast mitochondria. Reconstitution of ATP-32Pi exchange in the presence of phospholipids.", "content": "A purified preparation of the oligomycin-sensitive ATPase from yeast mitochondria has been shown to elicit an oligomycin- and uncoupler-senstitive ATP-32Pi exchange in the presence of phospholipids. Reconstitution was normally achieved by dialysis of an ATPase-phospholipid-cholate mixture. Following this procedure, vesicles with diameters between 200 and 1,500 A were seen by electron microscopy. As in mitochondria, ATPase activity in the reconstituted system was stimulated by a range of uncouplers which inhibited ATP-32Pi exchange. These and other findings suggest that the coupling mechanism may still be intact within the ATPase complex.", "contents": "Studies of the oligomycin-sensitive ATPase from yeast mitochondria. Reconstitution of ATP-32Pi exchange in the presence of phospholipids. A purified preparation of the oligomycin-sensitive ATPase from yeast mitochondria has been shown to elicit an oligomycin- and uncoupler-senstitive ATP-32Pi exchange in the presence of phospholipids. Reconstitution was normally achieved by dialysis of an ATPase-phospholipid-cholate mixture. Following this procedure, vesicles with diameters between 200 and 1,500 A were seen by electron microscopy. As in mitochondria, ATPase activity in the reconstituted system was stimulated by a range of uncouplers which inhibited ATP-32Pi exchange. These and other findings suggest that the coupling mechanism may still be intact within the ATPase complex."} {"id": "PMID:171521", "title": "Magnetic resonance and kinetic studies of the mechanism of membrane-bound sodium and potassium ion- activated adenosine triphosphatase.", "content": "EPR and water proton relaxation rate (1/T1) studies of partially (40%) and \"fully\" (90%) purified preparations of membrane-bound (Na+ + K+) activated ATPase from sheep kidney indicate one tight binding site for Mn2+ per enzyme dimer, with a dissociation constant (KD = 0.88 muM) in agreement with the kinetically determined activator constant, identifying this Mn2+-binding site as the active site of the ATPase. Competition studies indicate that Mg2+ binds at this site with a dissociation constant of 1 mM in agreement with its activator constant. Inorganic phosphate and methylphosphonate bind to the enzyme-Mn2+ complex with similar high affinities and decrease 1/T1 of water protons due to a decrease from four to three in the number of rapidly exchanging water protons in the coordination sphere of enzyme-bound Mn2+. The relative effectiveness of Na+ and K+ in facilitating ternary complex formation with HPO2-4 and CH3PO2-3 as a function of pH indicates that Na+ induces the phosphate monoanion to interact with enzyme-bound Mn2+. Thus protonation of an enzyme-bound phosphoryl group would convert a K+-binding site to a Na+-binding site. Dissociation constants for K+ and Na+, estimated from NMR titrations, agreed with kinetically determined activator constants of these ions consistent with binding to the active site. Parallel 32Pi-binding studies show negligible formation (less than 7%) of a covalent E-P complex under these conditions, indicating that the NMR method has detected an additional noncovalent intermediate in ion transport. Ouabain, which increases the extent of phosphorylation of the enzyme to 24% at pH 7.8 and to 106% at pH 6.1, produced further decreases in 1/T1 of water protons. Preliminary 31P- relaxation studies of CH3PO2-3 in the presence of ATPase and Mn2+ yield an Mn to P distance (6.9 +/- 0.5 A) suggesting a second sphere enzyme-Mn-ligand-CH3PO2-3 complex. Previous kinetic studies have shown that T1+ substitutes for K+ in the activation of the enzyme but competes with Na+ at higher levels. From the paramagnetic effect of Mn2+ at the active site on the enzyme on I/T1 of 205T1 bound at the Na+ site, a Mn2+ to T1+ distance of 4.0 +/- 0.1 A is calculated, suggesting the sharing of a common ligand atomy by Mn2+ and T1+ on the ATPase. Addition of Pi increases this distance to 5.4 A consistent with the insertion of P between Mn2+ and T1+. These results are consistent with a mechanism for the (Na+ + K+)-ATPase and for ion transport in which the ionization state of Pi at a single enzyme active site controls the binding and transport of Na+ and K+, and indicate that the transport site for monovalent cations is very near the catalytic site of the ATPase. Our mechanism also accounts for the order of magnitude weaker binding of Na+ compared to K+.", "contents": "Magnetic resonance and kinetic studies of the mechanism of membrane-bound sodium and potassium ion- activated adenosine triphosphatase. EPR and water proton relaxation rate (1/T1) studies of partially (40%) and \"fully\" (90%) purified preparations of membrane-bound (Na+ + K+) activated ATPase from sheep kidney indicate one tight binding site for Mn2+ per enzyme dimer, with a dissociation constant (KD = 0.88 muM) in agreement with the kinetically determined activator constant, identifying this Mn2+-binding site as the active site of the ATPase. Competition studies indicate that Mg2+ binds at this site with a dissociation constant of 1 mM in agreement with its activator constant. Inorganic phosphate and methylphosphonate bind to the enzyme-Mn2+ complex with similar high affinities and decrease 1/T1 of water protons due to a decrease from four to three in the number of rapidly exchanging water protons in the coordination sphere of enzyme-bound Mn2+. The relative effectiveness of Na+ and K+ in facilitating ternary complex formation with HPO2-4 and CH3PO2-3 as a function of pH indicates that Na+ induces the phosphate monoanion to interact with enzyme-bound Mn2+. Thus protonation of an enzyme-bound phosphoryl group would convert a K+-binding site to a Na+-binding site. Dissociation constants for K+ and Na+, estimated from NMR titrations, agreed with kinetically determined activator constants of these ions consistent with binding to the active site. Parallel 32Pi-binding studies show negligible formation (less than 7%) of a covalent E-P complex under these conditions, indicating that the NMR method has detected an additional noncovalent intermediate in ion transport. Ouabain, which increases the extent of phosphorylation of the enzyme to 24% at pH 7.8 and to 106% at pH 6.1, produced further decreases in 1/T1 of water protons. Preliminary 31P- relaxation studies of CH3PO2-3 in the presence of ATPase and Mn2+ yield an Mn to P distance (6.9 +/- 0.5 A) suggesting a second sphere enzyme-Mn-ligand-CH3PO2-3 complex. Previous kinetic studies have shown that T1+ substitutes for K+ in the activation of the enzyme but competes with Na+ at higher levels. From the paramagnetic effect of Mn2+ at the active site on the enzyme on I/T1 of 205T1 bound at the Na+ site, a Mn2+ to T1+ distance of 4.0 +/- 0.1 A is calculated, suggesting the sharing of a common ligand atomy by Mn2+ and T1+ on the ATPase. Addition of Pi increases this distance to 5.4 A consistent with the insertion of P between Mn2+ and T1+. These results are consistent with a mechanism for the (Na+ + K+)-ATPase and for ion transport in which the ionization state of Pi at a single enzyme active site controls the binding and transport of Na+ and K+, and indicate that the transport site for monovalent cations is very near the catalytic site of the ATPase. Our mechanism also accounts for the order of magnitude weaker binding of Na+ compared to K+."} {"id": "PMID:171522", "title": "Estrogen and estrogen receptors of breast cancer.", "content": "Human breast cancer can be divided into a group that contains specific receptor sites for estrogen and a group without such specific estrogen-binding sites. The presence of specific estrogen receptors in some tumors indicating hormonal dependency has been shown to be of predictive value for endocrine treatment. This would greatly improve therapeutic planning for patients with breast cancer. Tumor tissue from 52 patients was investigated for content of both cytosol estrogen and estrogen receptor. In addition, the total tumor estrogen was also determined in 14 of these tumors. The results of this investigation show two distinct groups: one group containing both estrogen receptor and estrogen and a second group with no receptor but with measurable amount of estrogen. Tumors with estrogen receptors have higher tissue levels of estrogen than tumors without specific estrogen receptor. Even in the absence of estrogen recptor, however, most tumor tissue examined contained a measurable amount of estrogen.", "contents": "Estrogen and estrogen receptors of breast cancer. Human breast cancer can be divided into a group that contains specific receptor sites for estrogen and a group without such specific estrogen-binding sites. The presence of specific estrogen receptors in some tumors indicating hormonal dependency has been shown to be of predictive value for endocrine treatment. This would greatly improve therapeutic planning for patients with breast cancer. Tumor tissue from 52 patients was investigated for content of both cytosol estrogen and estrogen receptor. In addition, the total tumor estrogen was also determined in 14 of these tumors. The results of this investigation show two distinct groups: one group containing both estrogen receptor and estrogen and a second group with no receptor but with measurable amount of estrogen. Tumors with estrogen receptors have higher tissue levels of estrogen than tumors without specific estrogen receptor. Even in the absence of estrogen recptor, however, most tumor tissue examined contained a measurable amount of estrogen."} {"id": "PMID:171523", "title": "Protective effect of methylprednisolone on the heart during ischemic arrest.", "content": "Although corticosteroids have been shown to stabilize lysosomal membranes and prevent release of hydrolytic enzymes, the mechanism of membrane stabilization remains obscure. The few reports regarding the use of steroids in myocardial ischemia have been conflicting. This study was undertaken to determine if a pharmacologic dose of the glucocorticoid methylprednisolone would protect the heart during ischemic cardiac arrest. A randomized double-blind study was performed in 25 dogs. Biochemical and hemodynamic parameters were assessed during and after cardiopulmonary bypass and after 30 minutes of ischemic cardiac arrest. Animals were divided into two groups. Group I served as controls and consisted of dogs injected intravenously with the vehicle of methylprednisolone 18 hours and 1 hour prior to experiment. Group II comprised dogs injected with methylprednisolone, 30 mg. per kilogram, IV, at the same time periods. Blood pH, gases, and electrolytes were measured; aortic, left atrial, and left ventricular pressures were monitored; the first derivative of the left ventricular pressure (dp/dt max.) was also determined. Arterial and coronary sinus blood samples were assayed for lactate levels and activity of the lysosomal enzyme, beta-glucuronidase. Left ventricular muscle was assayed for the nucleotides cyclic adenosine 3',5' monophosphate (AMP) and cyclic guanosine 3',5' monophosphate (GMP). Following restoration of coronary flow, mean aortic and left ventricular systolic pressures and left ventricular contractility as determined by dp/dt max. and dp/dt max./IP were depressed in both groups as expected but were significantly higher in Group II than in Group I (p less than 0.05). An increase in levels of both cyclic nucleotides occurred in each group during ischemia, but this increase in cyclic GMP was significantly greater in Group I (p less than 0.05). beta-glucuronidase activity and myocardial potassium loss as determined in coronary sinus blood were both significantly greater in Group I than in Group II (p less than 0.05). Results of this study demonstrate that pretreatment with a pharmacologic dose of methylprednisolone significantly enhances cardiac recovery after ischemia. Lysosomal membrane stability and modulation of cyclic GMP levels may be critical determinants in the mechanism of cardiac ischemia.", "contents": "Protective effect of methylprednisolone on the heart during ischemic arrest. Although corticosteroids have been shown to stabilize lysosomal membranes and prevent release of hydrolytic enzymes, the mechanism of membrane stabilization remains obscure. The few reports regarding the use of steroids in myocardial ischemia have been conflicting. This study was undertaken to determine if a pharmacologic dose of the glucocorticoid methylprednisolone would protect the heart during ischemic cardiac arrest. A randomized double-blind study was performed in 25 dogs. Biochemical and hemodynamic parameters were assessed during and after cardiopulmonary bypass and after 30 minutes of ischemic cardiac arrest. Animals were divided into two groups. Group I served as controls and consisted of dogs injected intravenously with the vehicle of methylprednisolone 18 hours and 1 hour prior to experiment. Group II comprised dogs injected with methylprednisolone, 30 mg. per kilogram, IV, at the same time periods. Blood pH, gases, and electrolytes were measured; aortic, left atrial, and left ventricular pressures were monitored; the first derivative of the left ventricular pressure (dp/dt max.) was also determined. Arterial and coronary sinus blood samples were assayed for lactate levels and activity of the lysosomal enzyme, beta-glucuronidase. Left ventricular muscle was assayed for the nucleotides cyclic adenosine 3',5' monophosphate (AMP) and cyclic guanosine 3',5' monophosphate (GMP). Following restoration of coronary flow, mean aortic and left ventricular systolic pressures and left ventricular contractility as determined by dp/dt max. and dp/dt max./IP were depressed in both groups as expected but were significantly higher in Group II than in Group I (p less than 0.05). An increase in levels of both cyclic nucleotides occurred in each group during ischemia, but this increase in cyclic GMP was significantly greater in Group I (p less than 0.05). beta-glucuronidase activity and myocardial potassium loss as determined in coronary sinus blood were both significantly greater in Group I than in Group II (p less than 0.05). Results of this study demonstrate that pretreatment with a pharmacologic dose of methylprednisolone significantly enhances cardiac recovery after ischemia. Lysosomal membrane stability and modulation of cyclic GMP levels may be critical determinants in the mechanism of cardiac ischemia."} {"id": "PMID:171524", "title": "Uremic neuropathy. III. Controlled study of restricted protein and fluid diet and infrequent hemodialysis versus conventional hemodialysis treatment.", "content": "The effect of a treatment schedule of restricted protein and fluid intake and of infrequent hemodialysis (schedule 1) as compared to a conventional hemodialysis treatment schedule (schedule 2) on the presence and severity of peripheral neuropathy has been studied in a small group of patients using a crossover design. Using the neurologic evaluation and quantitative assessment of cutaneous sensation and of nerve conduction as indices of peripheral nerve function, we have not demonstrated any worsening of peripheral nerve function from markedly curtailing the frequency of hemodialysis and modifying the diet. Because of the small size of the study, the preponderance of patients receiving the test treatment schedule first, and the possibility that nerve function slowly worsens with time, it is not possible to say with certainty that the test or the control treatment schedule might adversely affect peripheral nerve function. If such an effect is present it would appear to be small.", "contents": "Uremic neuropathy. III. Controlled study of restricted protein and fluid diet and infrequent hemodialysis versus conventional hemodialysis treatment. The effect of a treatment schedule of restricted protein and fluid intake and of infrequent hemodialysis (schedule 1) as compared to a conventional hemodialysis treatment schedule (schedule 2) on the presence and severity of peripheral neuropathy has been studied in a small group of patients using a crossover design. Using the neurologic evaluation and quantitative assessment of cutaneous sensation and of nerve conduction as indices of peripheral nerve function, we have not demonstrated any worsening of peripheral nerve function from markedly curtailing the frequency of hemodialysis and modifying the diet. Because of the small size of the study, the preponderance of patients receiving the test treatment schedule first, and the possibility that nerve function slowly worsens with time, it is not possible to say with certainty that the test or the control treatment schedule might adversely affect peripheral nerve function. If such an effect is present it would appear to be small."} {"id": "PMID:171527", "title": "Steroid binding properties of estradiol receptors in human breast cancer.", "content": "The incidence of a specific estradiol receptor among the Finnish breast cancer patients was investigated using methods involving dextran-coated charcoal or sucrose density gradient centrifugation techniques. An estradiol receptor was detected in 20 (71%) out of the 28 tumor specimens studied with the following binding site concentrations: 100-1000 fmoles/mg cytosol protein in 12 patients; 10-99 fmoles/mg cytosol protein in 6 patients and below 10 fmoles/mg cytosol protein in 2 patients the lowest detectable level being about 5 fmoles/mg cytosol protein. The apparent intrinsic association constant of the receptor for estradiol-17 beta ranged from 0.4-32 X 10(10) liters/mole in different breast cancer specimens. Estradiol receptor concentration did not seem to correlate well with the age of the patients or the microscopic structure of the tumor. The ligand-binding specificity of the receptor was studied with 25 different estrogen derivatives in 6 separate tumor specimens. The binding proteins in all these tumors showed very similar ligand specificities, despite differences in their histological types and estradiol-binding site concentrations. The phenolic hydroxyl group at C--3 was essential for an effective binding by the receptor, whereas certain modifications in the D-ring structure were well tolerated. As is the case with other steroid receptors, certain hydrophobic substituents seemed to increase the binding of the ligand by the breast cancer estradiol receptor. The in vitro binding affinity and the in vivo biological (estrogenic) potency of some of the steroids investigated did not correlate very well.", "contents": "Steroid binding properties of estradiol receptors in human breast cancer. The incidence of a specific estradiol receptor among the Finnish breast cancer patients was investigated using methods involving dextran-coated charcoal or sucrose density gradient centrifugation techniques. An estradiol receptor was detected in 20 (71%) out of the 28 tumor specimens studied with the following binding site concentrations: 100-1000 fmoles/mg cytosol protein in 12 patients; 10-99 fmoles/mg cytosol protein in 6 patients and below 10 fmoles/mg cytosol protein in 2 patients the lowest detectable level being about 5 fmoles/mg cytosol protein. The apparent intrinsic association constant of the receptor for estradiol-17 beta ranged from 0.4-32 X 10(10) liters/mole in different breast cancer specimens. Estradiol receptor concentration did not seem to correlate well with the age of the patients or the microscopic structure of the tumor. The ligand-binding specificity of the receptor was studied with 25 different estrogen derivatives in 6 separate tumor specimens. The binding proteins in all these tumors showed very similar ligand specificities, despite differences in their histological types and estradiol-binding site concentrations. The phenolic hydroxyl group at C--3 was essential for an effective binding by the receptor, whereas certain modifications in the D-ring structure were well tolerated. As is the case with other steroid receptors, certain hydrophobic substituents seemed to increase the binding of the ligand by the breast cancer estradiol receptor. The in vitro binding affinity and the in vivo biological (estrogenic) potency of some of the steroids investigated did not correlate very well."} {"id": "PMID:171538", "title": "Changes in the composition and physico-chemical characteristics of serum lipoproteins during ethanol-induced lipaemia in alcoholic subjects.", "content": "The effect upon serum lipids and lipoproteins of a large intake of ethanol (180 g in 6 hr) has been studied during the ensuing 24 hr in 21 subjects. These were all men who were habituated to heavy drinking but who were shown to be normolipaemic when maintained on a normal diet with a restricted intake of alcohol. In all the subjects studied, ingestion of this amount of ethanol induced an acute hypertriglyceridaemia which varied in intensity between individuals, with increases ranging from 26% to 377% above the basal value. On the other hand, no significant change occurred in plasma cholesterol. In addition to measurements of triglycerides and cholesterol, the plasma from all the subjects were examined by electrophoresis in agarose and polyacrylamide gels with photometric scanning of the gels. In a subgroup of ten of the subjects, the plasma lipoproteins were separated into very low density (VLDL), low-density (LDL), and high-density (HDL) fractions, which were also analyzed biochemically and by electrophoresis. Following ethanol ingestion, a mean increase of about twofold in triglyceride content, and a decrease in the cholesterol/triglyceride ratio was observed in VLDL, LDL, and HDL. The triglyceride/protein ratio decreased in VLDL and increased in LDL. On electrophoresis of the intact sera following ethanol ingestion visible particulate fat and a band which failed to permeate the gel ('chylomicron-like band') was observed in five out of ten subjects and eight out of these ten subjects showed a prominent prebetalipoprotein (pre-beta) band. This component was found to be present in the lipoprotein fraction of density greater than 1.006 Kg/1. Examination of this fraction from basal specimens revealed a pre-beta band in only two of the ten subjects and the intensity of this band increased in the corresponding fractions from the same subjects after ethanol ingestion. In an additional four subjects no pre-beta was detected in this fraction before ethanol but appeared after ethanol ingestion. No attempt has been made to characterize further the component with these characters but it is suggested that it is probably an intermediate lipoprotein (ILDL), that is, a lipoprotein with characteristics intermediate between VLDL and LDL.", "contents": "Changes in the composition and physico-chemical characteristics of serum lipoproteins during ethanol-induced lipaemia in alcoholic subjects. The effect upon serum lipids and lipoproteins of a large intake of ethanol (180 g in 6 hr) has been studied during the ensuing 24 hr in 21 subjects. These were all men who were habituated to heavy drinking but who were shown to be normolipaemic when maintained on a normal diet with a restricted intake of alcohol. In all the subjects studied, ingestion of this amount of ethanol induced an acute hypertriglyceridaemia which varied in intensity between individuals, with increases ranging from 26% to 377% above the basal value. On the other hand, no significant change occurred in plasma cholesterol. In addition to measurements of triglycerides and cholesterol, the plasma from all the subjects were examined by electrophoresis in agarose and polyacrylamide gels with photometric scanning of the gels. In a subgroup of ten of the subjects, the plasma lipoproteins were separated into very low density (VLDL), low-density (LDL), and high-density (HDL) fractions, which were also analyzed biochemically and by electrophoresis. Following ethanol ingestion, a mean increase of about twofold in triglyceride content, and a decrease in the cholesterol/triglyceride ratio was observed in VLDL, LDL, and HDL. The triglyceride/protein ratio decreased in VLDL and increased in LDL. On electrophoresis of the intact sera following ethanol ingestion visible particulate fat and a band which failed to permeate the gel ('chylomicron-like band') was observed in five out of ten subjects and eight out of these ten subjects showed a prominent prebetalipoprotein (pre-beta) band. This component was found to be present in the lipoprotein fraction of density greater than 1.006 Kg/1. Examination of this fraction from basal specimens revealed a pre-beta band in only two of the ten subjects and the intensity of this band increased in the corresponding fractions from the same subjects after ethanol ingestion. In an additional four subjects no pre-beta was detected in this fraction before ethanol but appeared after ethanol ingestion. No attempt has been made to characterize further the component with these characters but it is suggested that it is probably an intermediate lipoprotein (ILDL), that is, a lipoprotein with characteristics intermediate between VLDL and LDL."} {"id": "PMID:171539", "title": "Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds.", "content": "A newly recognized familial hyperlipoproteinemia, familial hyper-alpha-lipoproteinemia, is described in 18 kindreds. Affected probands and relatives had distinctive elevations of alpha-lipoprotein cholesterol (C-HDL), slight elevations of total cholesterol, no elevation of LDL and VLDL cholesterol, and normal triglyceride levels. The proband and at least one additional first degree relative had distinctive elevations of C-HDL in 16 of 18 kindreds. Simple segregation analysis involving 84 offspring of 22 hyper-alpha X normal-alpha matings from these 16 kindreds revealed a ratio of hyper-alpha to normal of 37:47, a ratio not significantly different from 1:1 (chi 2(1) = 1.2), the ratio consistent with autosomal dominant transmission. Despite the suggestion of a major gene effect by this analysis, evaluation of the C-HDL distribution in kindred members failed to reveal bimodality, and familial correlation analysis revealed no parent-offspring correlation. The present data suggest that an environmental cause common to sibships is possibly important in causing the disorder. Longevity analysis demonstrated elongation of life expectancy for kindred members, and there was an apparent rarity of premature cardiac events.", "contents": "Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds. A newly recognized familial hyperlipoproteinemia, familial hyper-alpha-lipoproteinemia, is described in 18 kindreds. Affected probands and relatives had distinctive elevations of alpha-lipoprotein cholesterol (C-HDL), slight elevations of total cholesterol, no elevation of LDL and VLDL cholesterol, and normal triglyceride levels. The proband and at least one additional first degree relative had distinctive elevations of C-HDL in 16 of 18 kindreds. Simple segregation analysis involving 84 offspring of 22 hyper-alpha X normal-alpha matings from these 16 kindreds revealed a ratio of hyper-alpha to normal of 37:47, a ratio not significantly different from 1:1 (chi 2(1) = 1.2), the ratio consistent with autosomal dominant transmission. Despite the suggestion of a major gene effect by this analysis, evaluation of the C-HDL distribution in kindred members failed to reveal bimodality, and familial correlation analysis revealed no parent-offspring correlation. The present data suggest that an environmental cause common to sibships is possibly important in causing the disorder. Longevity analysis demonstrated elongation of life expectancy for kindred members, and there was an apparent rarity of premature cardiac events."} {"id": "PMID:171542", "title": "Uptake of radioactive DOPA by Mycobacterium leprae in vitro.", "content": "Our previous studies demonstrated that Mycobacterium leprae contains a characteristic o-diphenoloxidase which converts a variety of phenolic compounds to quinones in vitro. This enzyme was not present in any other mycobacteria tested. The results reported here deal with the uptake and binding of radioactive DOPA by M. leprae. The leprosy bacilli incubated with tritium-labelled DOPA, readily took up the substrate. The binding of DOPA by the bacilli was markedly inhibited by diethyldithiocarbamate. The organisms also bound tritiated norepinephrine. Mycobacterium phlei which does not oxidize phenolic substrates failed to bind DOPA. Cultures of melanocytes which contain o-diphenoloxidase took up tritiated DOPA. Catecholamine metabolism is known to be important in myocardial cells. Cultures of turtle-heart cells did not oxidize DOPA to quinone; however, these cells bound the labelled substrate. A cell line of fibroblasts derived from armadillo skin neither oxidized nor took up DOPA. The results indicate that, like melanocytes and turtle-heart cells, M. leprae probably possesses specific receptor sites for the binding and subsequent metabolism of phenolic substrates.", "contents": "Uptake of radioactive DOPA by Mycobacterium leprae in vitro. Our previous studies demonstrated that Mycobacterium leprae contains a characteristic o-diphenoloxidase which converts a variety of phenolic compounds to quinones in vitro. This enzyme was not present in any other mycobacteria tested. The results reported here deal with the uptake and binding of radioactive DOPA by M. leprae. The leprosy bacilli incubated with tritium-labelled DOPA, readily took up the substrate. The binding of DOPA by the bacilli was markedly inhibited by diethyldithiocarbamate. The organisms also bound tritiated norepinephrine. Mycobacterium phlei which does not oxidize phenolic substrates failed to bind DOPA. Cultures of melanocytes which contain o-diphenoloxidase took up tritiated DOPA. Catecholamine metabolism is known to be important in myocardial cells. Cultures of turtle-heart cells did not oxidize DOPA to quinone; however, these cells bound the labelled substrate. A cell line of fibroblasts derived from armadillo skin neither oxidized nor took up DOPA. The results indicate that, like melanocytes and turtle-heart cells, M. leprae probably possesses specific receptor sites for the binding and subsequent metabolism of phenolic substrates."} {"id": "PMID:171543", "title": "[Standardized fight against cancer in childhood (author's transl)].", "content": "The 5-year experiences of a center for pediatric oncology in a children's university hospital are reported. Currently (1-1-1975) 60 of 135 treated leukemic and 88 of 152 treated tumor patients are living. 1974, there were in the average 34 ambulatory complete blood counts per week, and in addition 263 bone marrow and 196 ambulatory lumbar punctures per year. The standardized routine of an outpatient visit is described. Advice for parents and family physicians are given. A standardized diagnostic approach for M. Hodgkin as a prototype is proposed, and a standardized therapy for Wilms' tumor. Of 24 thus treated children with Wilms' tumor 16 (\"67 p.c.\") survive, included 7 of 15 (\"47 p.c.\") with metastasized disease (observation time 21-71 months). Current treatment of 49 children with acute lymphoblastic leukemia resulted in continuous complete remission of 22 patients (\"45 p.c.\") (observation time 1-4 years), but 6 dead in complete remission due to infection. The need for specialized treatment centers with skilled persons is emphasized.", "contents": "[Standardized fight against cancer in childhood (author's transl)]. The 5-year experiences of a center for pediatric oncology in a children's university hospital are reported. Currently (1-1-1975) 60 of 135 treated leukemic and 88 of 152 treated tumor patients are living. 1974, there were in the average 34 ambulatory complete blood counts per week, and in addition 263 bone marrow and 196 ambulatory lumbar punctures per year. The standardized routine of an outpatient visit is described. Advice for parents and family physicians are given. A standardized diagnostic approach for M. Hodgkin as a prototype is proposed, and a standardized therapy for Wilms' tumor. Of 24 thus treated children with Wilms' tumor 16 (\"67 p.c.\") survive, included 7 of 15 (\"47 p.c.\") with metastasized disease (observation time 21-71 months). Current treatment of 49 children with acute lymphoblastic leukemia resulted in continuous complete remission of 22 patients (\"45 p.c.\") (observation time 1-4 years), but 6 dead in complete remission due to infection. The need for specialized treatment centers with skilled persons is emphasized."} {"id": "PMID:171546", "title": "[About the plurality of the manifestations of cytomegalovirus infection in adult (author's transl)].", "content": "Three various cases of cytomegalovirus infection will be described. At first will be represented a double infection of cytomegalovirus and toxoplasmosis. In the second case it's about the organmanifestation of cytomegalovirus of the liver as hepatitis. At last will be discussed a severe infection of the central nervous system on the one hand in form of Guillain-Barr\u00e9-syndrome, on the other hand manifestated as encephalitis.", "contents": "[About the plurality of the manifestations of cytomegalovirus infection in adult (author's transl)]. Three various cases of cytomegalovirus infection will be described. At first will be represented a double infection of cytomegalovirus and toxoplasmosis. In the second case it's about the organmanifestation of cytomegalovirus of the liver as hepatitis. At last will be discussed a severe infection of the central nervous system on the one hand in form of Guillain-Barr\u00e9-syndrome, on the other hand manifestated as encephalitis."} {"id": "PMID:171547", "title": "[Experiences in the management of patients with ileo- and colostomy (author's transl)].", "content": "In the presented paper the management of stoma-patients has been discussed. Two topics had to be seen, first the psychological guidance of the patient and his reentry into society and second the management of the stoma itself. Beside of the sometimes unavoidable complications the patients are often molested by preventable inconviences as skin-irritation, soiling, and odors. New progresses have been made by the development of scentless skin pelottes and adhesive folias. With a new adhesive tissue which avoids the contact between the skin and the adhesive folia we can prevent the skin irritations previously nearly unavoidable.", "contents": "[Experiences in the management of patients with ileo- and colostomy (author's transl)]. In the presented paper the management of stoma-patients has been discussed. Two topics had to be seen, first the psychological guidance of the patient and his reentry into society and second the management of the stoma itself. Beside of the sometimes unavoidable complications the patients are often molested by preventable inconviences as skin-irritation, soiling, and odors. New progresses have been made by the development of scentless skin pelottes and adhesive folias. With a new adhesive tissue which avoids the contact between the skin and the adhesive folia we can prevent the skin irritations previously nearly unavoidable."} {"id": "PMID:171548", "title": "[Different forms of hyperlipoproteinemia in diabetics (author's transl)].", "content": "Plasma lipoprotein patterns currently employed in attempts to identify different forms of hyperlipoproteinemia have been investigated in 113 hospitalized diabetics. For classification two methods have been compared: The first is based on lipid electrophoresis pattern in agarose gel coupled with the measurement of triglycerides and cholesterol. The second is based on plasma lipoprotein pattern obtained by separation of lipoproteins on cellulose acetate and following densitometry combined with estimation of cholesterol and beta-cholesterol and triglycerides in plasma. It could be demonstrated, that the results obtained in agarose system are not convertible to data obtained with the method for quantifying lipoproteins. By quantitative analysis only 4 p.c. of diabetics had type IIa, 4 p.c. type V, the others type IIb or IV. Graphic plots and calculated concentrations of lipoproteins gave differences in lipoprotein profiles between compensated and acidotic diabetics. In diabetes stage 1 most values are in the normal range, in stage 2 prebetalipoproteins increase and betalipoproteins decrease. In some case betalipoproteins are elevated and prebetalipoproteins diminished. In stage 3 with metabolic acidosis we observed an altered lipoprotein profile with confluence of beta- and prebeta-peak. The calculated concentration profile was also different from the others and revealed no certain quantitative information described for other electropherograms containing alpha, beta- and prebeta-bands. This phenomenon was frequently observed in patients with acute viral hepatitis and severe chronic liver disease. The pattern in diabetics is representative for patients with an excess of plasma lipids (the 2.5 fold of normal values in the mean). It is characterised as a broad beta band on the electropherogram similar to type III pattern. Presence of beta migrating lipoproteins in the ultracentrifugal supernatand fraction of d = 1006 could not be demonstrated.", "contents": "[Different forms of hyperlipoproteinemia in diabetics (author's transl)]. Plasma lipoprotein patterns currently employed in attempts to identify different forms of hyperlipoproteinemia have been investigated in 113 hospitalized diabetics. For classification two methods have been compared: The first is based on lipid electrophoresis pattern in agarose gel coupled with the measurement of triglycerides and cholesterol. The second is based on plasma lipoprotein pattern obtained by separation of lipoproteins on cellulose acetate and following densitometry combined with estimation of cholesterol and beta-cholesterol and triglycerides in plasma. It could be demonstrated, that the results obtained in agarose system are not convertible to data obtained with the method for quantifying lipoproteins. By quantitative analysis only 4 p.c. of diabetics had type IIa, 4 p.c. type V, the others type IIb or IV. Graphic plots and calculated concentrations of lipoproteins gave differences in lipoprotein profiles between compensated and acidotic diabetics. In diabetes stage 1 most values are in the normal range, in stage 2 prebetalipoproteins increase and betalipoproteins decrease. In some case betalipoproteins are elevated and prebetalipoproteins diminished. In stage 3 with metabolic acidosis we observed an altered lipoprotein profile with confluence of beta- and prebeta-peak. The calculated concentration profile was also different from the others and revealed no certain quantitative information described for other electropherograms containing alpha, beta- and prebeta-bands. This phenomenon was frequently observed in patients with acute viral hepatitis and severe chronic liver disease. The pattern in diabetics is representative for patients with an excess of plasma lipids (the 2.5 fold of normal values in the mean). It is characterised as a broad beta band on the electropherogram similar to type III pattern. Presence of beta migrating lipoproteins in the ultracentrifugal supernatand fraction of d = 1006 could not be demonstrated."} {"id": "PMID:171550", "title": "Envelope and nucleocapsid antigens of Cytomegalovirus (CMV).", "content": "A method for the purification and concentration of Cytomegalovirus nucleocapsids and particles complete with envelope is described. Antibody to either nucleocapsid or envelope antigens can be detected in human sera. In patients with CMV disease the antibodies to the envelope antigen could not be detected before the 3rd week after the beginning of disease whereas antibodies to the nucleocapsid were detected earlier.", "contents": "Envelope and nucleocapsid antigens of Cytomegalovirus (CMV). A method for the purification and concentration of Cytomegalovirus nucleocapsids and particles complete with envelope is described. Antibody to either nucleocapsid or envelope antigens can be detected in human sera. In patients with CMV disease the antibodies to the envelope antigen could not be detected before the 3rd week after the beginning of disease whereas antibodies to the nucleocapsid were detected earlier."} {"id": "PMID:171553", "title": "Multiple regulation of nucleoside catabolizing enzymes: regulation of the deo operon by the cytR and deoR gene products.", "content": "The protein and repressor nature of two regulatory gene products in E. coli has been demonstrated, employing mutants with either amber or thermosensitive mutations. The regulatory genes are the cytR and the deoR genes, both of which contribute to the regulation of the synthesis of nucleoside catabolizing enzymes. Enzyme levels in strains with concurrent mutations in both regulatory genes are considerably higher than the sum of the levels in strains with a cytR or a deoR mutation alone, indicating a certain co-operativity between the two repressor proteins. The glucose repression of enzyme levels observed in the double regulatory mutant is similar to that found in a cytR mutant, and much more pronounced than the glucose effect in a deoR mutant. A model of the promoter-operator region in the deo operon is proposed.", "contents": "Multiple regulation of nucleoside catabolizing enzymes: regulation of the deo operon by the cytR and deoR gene products. The protein and repressor nature of two regulatory gene products in E. coli has been demonstrated, employing mutants with either amber or thermosensitive mutations. The regulatory genes are the cytR and the deoR genes, both of which contribute to the regulation of the synthesis of nucleoside catabolizing enzymes. Enzyme levels in strains with concurrent mutations in both regulatory genes are considerably higher than the sum of the levels in strains with a cytR or a deoR mutation alone, indicating a certain co-operativity between the two repressor proteins. The glucose repression of enzyme levels observed in the double regulatory mutant is similar to that found in a cytR mutant, and much more pronounced than the glucose effect in a deoR mutant. A model of the promoter-operator region in the deo operon is proposed."} {"id": "PMID:171554", "title": "Information contained in the amino acid sequence of the alpha1(I)-chain of collagen and its consequences upon the formation of the triple helix, of fibrils and crosslinks.", "content": "The molecule of type I collagen from skin consists of two alpha1(I)-chains and one alpha2-chain. The sequence of the entire alpha1-chain comprising 1052 residues is summarily presented and discussed. Apart from the 279 residues of alpha1(I)-CB8 whose sequence has been established for rat skin collagen, all sequences have been determined for calf skin collagen. In order to facilitate sequence analysis, the alpha1-chain was cleaved into defined fragments by cyanogen bromide or hydroxylamine or limited collagenase digestion. Most of the sequence was established by automated stepwise Edman degradation. The alpha1-chain contains two basically different types of sequences: the triple helical region of 1011 amino acid residues in which every third position is occupied by glycine and the N- and C-terminal regions not displaying this type of regularity. Both of these non-triple helical regions carry oxidizable lysine or hydroxylysine residues as functional sites for the intermolecular crosslink formation. Implications of the amino acid sequence for the stability of the triple helix and the fibril as well as for formation of crosslinks are discussed. Evaluation of the sequence in connection with electron microscopical investigations yielded the parameters of the axial arrangement of the molecules within the fibrils. Axial stagger of the molecules by a distance D = 670 angstrom = 233 amino acid residues results in maximal interaction of polar sequence regions of adjacent molecules and similarly of regions of hydrophobic residues. Ordered aggregation of molecules into fibrils is, therefore, regulated by electrostatic and electrophobic forces. Possible loci of intermolecular crosslinks between the alpha1-chains of adjacent molecules may be deduced from the dimensions of the axial aggregation of molecules.", "contents": "Information contained in the amino acid sequence of the alpha1(I)-chain of collagen and its consequences upon the formation of the triple helix, of fibrils and crosslinks. The molecule of type I collagen from skin consists of two alpha1(I)-chains and one alpha2-chain. The sequence of the entire alpha1-chain comprising 1052 residues is summarily presented and discussed. Apart from the 279 residues of alpha1(I)-CB8 whose sequence has been established for rat skin collagen, all sequences have been determined for calf skin collagen. In order to facilitate sequence analysis, the alpha1-chain was cleaved into defined fragments by cyanogen bromide or hydroxylamine or limited collagenase digestion. Most of the sequence was established by automated stepwise Edman degradation. The alpha1-chain contains two basically different types of sequences: the triple helical region of 1011 amino acid residues in which every third position is occupied by glycine and the N- and C-terminal regions not displaying this type of regularity. Both of these non-triple helical regions carry oxidizable lysine or hydroxylysine residues as functional sites for the intermolecular crosslink formation. Implications of the amino acid sequence for the stability of the triple helix and the fibril as well as for formation of crosslinks are discussed. Evaluation of the sequence in connection with electron microscopical investigations yielded the parameters of the axial arrangement of the molecules within the fibrils. Axial stagger of the molecules by a distance D = 670 angstrom = 233 amino acid residues results in maximal interaction of polar sequence regions of adjacent molecules and similarly of regions of hydrophobic residues. Ordered aggregation of molecules into fibrils is, therefore, regulated by electrostatic and electrophobic forces. Possible loci of intermolecular crosslinks between the alpha1-chains of adjacent molecules may be deduced from the dimensions of the axial aggregation of molecules."} {"id": "PMID:171555", "title": "Effect of NAD on flounder muscle glyceraldehyde 3-phosphate dehydrogenase.", "content": "Flounder muscle (Pseudopleuronectes americanus) glyceraldehyde-3-phosphate dehydrogenase was characterized as to its stability towards various inactivating treatments in the presence and absence of the enzyme cofactor, NAD. Incubation of a partially purified enzyme preparation at urea concentrations greater than 2 M produced a very rapid inactivation. NAD greatly reduced the rate of inactivation at all the urea concentrations tested. Incubation of each of the three major muscle enzyme forms in 0.1 percent trypsin or chymotrypsin for forty-five minutes decreased the activity of each form by 65 percent and 55 percent, respectively. NAD (5mM) afforded complete protection to each enzyme form from proteolytic digestion by these two enzymes. Exposure of each form to 50 degrees or 20 mM ATP also led to gross inactivation which could be greatly reduced if the respective incubations were performed in the presence of 5mM NAD. NAD was also found to be required for the renaturation of the unfolded urea-denatured subunits to form the active tetramer.", "contents": "Effect of NAD on flounder muscle glyceraldehyde 3-phosphate dehydrogenase. Flounder muscle (Pseudopleuronectes americanus) glyceraldehyde-3-phosphate dehydrogenase was characterized as to its stability towards various inactivating treatments in the presence and absence of the enzyme cofactor, NAD. Incubation of a partially purified enzyme preparation at urea concentrations greater than 2 M produced a very rapid inactivation. NAD greatly reduced the rate of inactivation at all the urea concentrations tested. Incubation of each of the three major muscle enzyme forms in 0.1 percent trypsin or chymotrypsin for forty-five minutes decreased the activity of each form by 65 percent and 55 percent, respectively. NAD (5mM) afforded complete protection to each enzyme form from proteolytic digestion by these two enzymes. Exposure of each form to 50 degrees or 20 mM ATP also led to gross inactivation which could be greatly reduced if the respective incubations were performed in the presence of 5mM NAD. NAD was also found to be required for the renaturation of the unfolded urea-denatured subunits to form the active tetramer."} {"id": "PMID:171557", "title": "Regulation of mammalian pyruvate dehydrogenase.", "content": "In mammalian tissues, two types of regulation of the pyruvate dehydrogenase complex have been described: end product inhibition by acetyl CoA and NADH: and the interconversion of an inactive phosphorylated form and an active nonphosphorylated form by an ATP requiring kinase and a specific phosphatase. This article is largely concerned with the latter type of regulation of the complex in adipose tissue by insulin (and other hormones) and in heart muscle by lipid fuels. Effectors of the two interconverting enzymes include pyruvate and ADP which inhibit the kinase, acetoin which activates the kinase and Ca2+ and Mg2+ which both activate the phosphatase and inhibit the kinase. Evidence is presented that all components of the pyruvate dehydrogenase complex including the phosphatase and kinase are located within the inner mitochondrial membrane. Direct measurements of the matrix concentration of substrates and effectors is not possible by techniques presently available. This is the key problem in the identification of the mechansims involved in the alterations in pyruvate dehydrogenase activity observed in adipose tissue and muscle. A number of indirect approaches have been used and these are reviewed. Most hopeful is the recent finding in this laboratory that in both adipose tissue and heart muscle, differences in activity of pyruvate dehydrogenase in the intact tissue persist during preparation and subsequent incubation of mitochondria.", "contents": "Regulation of mammalian pyruvate dehydrogenase. In mammalian tissues, two types of regulation of the pyruvate dehydrogenase complex have been described: end product inhibition by acetyl CoA and NADH: and the interconversion of an inactive phosphorylated form and an active nonphosphorylated form by an ATP requiring kinase and a specific phosphatase. This article is largely concerned with the latter type of regulation of the complex in adipose tissue by insulin (and other hormones) and in heart muscle by lipid fuels. Effectors of the two interconverting enzymes include pyruvate and ADP which inhibit the kinase, acetoin which activates the kinase and Ca2+ and Mg2+ which both activate the phosphatase and inhibit the kinase. Evidence is presented that all components of the pyruvate dehydrogenase complex including the phosphatase and kinase are located within the inner mitochondrial membrane. Direct measurements of the matrix concentration of substrates and effectors is not possible by techniques presently available. This is the key problem in the identification of the mechansims involved in the alterations in pyruvate dehydrogenase activity observed in adipose tissue and muscle. A number of indirect approaches have been used and these are reviewed. Most hopeful is the recent finding in this laboratory that in both adipose tissue and heart muscle, differences in activity of pyruvate dehydrogenase in the intact tissue persist during preparation and subsequent incubation of mitochondria."} {"id": "PMID:171561", "title": "[Importance of humoral mediators for the pathogenesis and treatment of migraine (author's transl)].", "content": "The vascular mechanism of migraine attacks -- intracranial vasoconstriction during the prodromal stage and passive vasodilatation of extracranial arteries during the painful phase -- has been confirmed by modern methods. In addition, number of humoral factors -- plasmakinin, serotonin, histamine -- intervene in the chain of events that culminates in migraine headache. In addition to these three humoral mediators, the part played by tyramine in migraine of alimentary origin, the precipitating effect of oestrogen decrease in menstrual migraine and the hypothetical role of prostaglandins and prolactin are discussed. The multifactorial mechanism of migraine accounts for the very variable profiles of effective anti-migraine drugs.", "contents": "[Importance of humoral mediators for the pathogenesis and treatment of migraine (author's transl)]. The vascular mechanism of migraine attacks -- intracranial vasoconstriction during the prodromal stage and passive vasodilatation of extracranial arteries during the painful phase -- has been confirmed by modern methods. In addition, number of humoral factors -- plasmakinin, serotonin, histamine -- intervene in the chain of events that culminates in migraine headache. In addition to these three humoral mediators, the part played by tyramine in migraine of alimentary origin, the precipitating effect of oestrogen decrease in menstrual migraine and the hypothetical role of prostaglandins and prolactin are discussed. The multifactorial mechanism of migraine accounts for the very variable profiles of effective anti-migraine drugs."} {"id": "PMID:171562", "title": "[Polyneuropathy in vitamin B 12 and folic acid deficiency. Clinical and histopathological study with electron-microscopy analysis of the sural nerve].", "content": "One case each of pernicious anemia and folic acid deficiency with chronic malabsorption with disease of the cord and histologically demonstrated concomitant disease of the peripheral nerve system in the sense of a polyneuropathy are described. The histological findings of nerve obtained by biopsy show, in both cases, the loss of individual nerve fibers as an expression of a chronic axonal degeneration. The pathogenetic basis to be considered in these cases is presented.", "contents": "[Polyneuropathy in vitamin B 12 and folic acid deficiency. Clinical and histopathological study with electron-microscopy analysis of the sural nerve]. One case each of pernicious anemia and folic acid deficiency with chronic malabsorption with disease of the cord and histologically demonstrated concomitant disease of the peripheral nerve system in the sense of a polyneuropathy are described. The histological findings of nerve obtained by biopsy show, in both cases, the loss of individual nerve fibers as an expression of a chronic axonal degeneration. The pathogenetic basis to be considered in these cases is presented."} {"id": "PMID:171563", "title": "[Secretion of insulin. Hypotheses at present under discussion (author's transl)].", "content": "Proinsulin is dissociated into insulin and C-peptide in the Golgi zone and in the beta-granules which fulfil a storage and transport function at the same time. Through an active transport process involving the microtubular and microfilament cytoplasmic system, the granules arrive at the cell wall and there they are emiocytotically excreted. At a still completely unknown spot on this secretory route, control of the secretion rate by calcium ions and cAMP-dependent phosphorylation seems possible. Calcium and cAMP as signal transmitters are again subject to the positive and negative modulating receptor-transmitted effect of adrenergic and cholinergic transmitter substances and beta-cytotropic peptide hormones. The basis of every modulation of the secretory function, however, is a secretion signal dependent on the concentration of glucose itself and glucose metabolites (only one?) on the one hand, and on the other on the energy resulting from endoxidation of glucose in the form of high energy phosphates.", "contents": "[Secretion of insulin. Hypotheses at present under discussion (author's transl)]. Proinsulin is dissociated into insulin and C-peptide in the Golgi zone and in the beta-granules which fulfil a storage and transport function at the same time. Through an active transport process involving the microtubular and microfilament cytoplasmic system, the granules arrive at the cell wall and there they are emiocytotically excreted. At a still completely unknown spot on this secretory route, control of the secretion rate by calcium ions and cAMP-dependent phosphorylation seems possible. Calcium and cAMP as signal transmitters are again subject to the positive and negative modulating receptor-transmitted effect of adrenergic and cholinergic transmitter substances and beta-cytotropic peptide hormones. The basis of every modulation of the secretory function, however, is a secretion signal dependent on the concentration of glucose itself and glucose metabolites (only one?) on the one hand, and on the other on the energy resulting from endoxidation of glucose in the form of high energy phosphates."} {"id": "PMID:171564", "title": "[Clofibrate treatment of diabetics with hyperproteinemias (author's transl)].", "content": "The effect of a six weeks clofibrate treatment on lipid metabolism was investigated in a collective of 38 constantly maladjusted elderly diabetics with an average of 30% overweight and various forms of hyperlipoproteinemias. Clofibrate produced a significant lowering of the mean triglyceride and cholesterol levels, whereas no such effect was observed in an untreated control group. Related to the various types of hyperlipoproteinemia (IIa, IIb and IV), the group treated with clofibrate showed a rate of normalization of nearly 50%, while the rate of improvement in the untreated control group was 10%.", "contents": "[Clofibrate treatment of diabetics with hyperproteinemias (author's transl)]. The effect of a six weeks clofibrate treatment on lipid metabolism was investigated in a collective of 38 constantly maladjusted elderly diabetics with an average of 30% overweight and various forms of hyperlipoproteinemias. Clofibrate produced a significant lowering of the mean triglyceride and cholesterol levels, whereas no such effect was observed in an untreated control group. Related to the various types of hyperlipoproteinemia (IIa, IIb and IV), the group treated with clofibrate showed a rate of normalization of nearly 50%, while the rate of improvement in the untreated control group was 10%."} {"id": "PMID:171567", "title": "The transplanted kidney as a source of cytomegalovirus infection.", "content": "To determine the incidence of cytomegalovirus infection in renal-transplant recipients we followed 32 prospectively for six months after operation. As judged by serologic change and virus isolation the infection rate for the entire group was 66 per cent (21 of 32 patients) - 59 per cent (13 of 22) for seronegative patients and 80 per cent (eight of 10) for seropositive patients. Of 10 seronegative patients who received kidneys from seronegative donors, only three became infected. However, of 12 seronegative patients who received kidneys from seropositive donors, 10 became infected. Thus, there was a significant correlation between development of infection and seropositivity of the donor (P = 0.03), particularly when the recipient was seronegative (P = 0.02). Five possible and four definite recognizable clinical illnesses were associated with cytomegalovirus infection; all except two were in initially seronegative subjects who received kidneys from seropositive donors. Primary infection and disease in nonimmune recipients may be caused by cytomegalovirus transmitted by the kidneys of latently infected seropositive donors.", "contents": "The transplanted kidney as a source of cytomegalovirus infection. To determine the incidence of cytomegalovirus infection in renal-transplant recipients we followed 32 prospectively for six months after operation. As judged by serologic change and virus isolation the infection rate for the entire group was 66 per cent (21 of 32 patients) - 59 per cent (13 of 22) for seronegative patients and 80 per cent (eight of 10) for seropositive patients. Of 10 seronegative patients who received kidneys from seronegative donors, only three became infected. However, of 12 seronegative patients who received kidneys from seropositive donors, 10 became infected. Thus, there was a significant correlation between development of infection and seropositivity of the donor (P = 0.03), particularly when the recipient was seronegative (P = 0.02). Five possible and four definite recognizable clinical illnesses were associated with cytomegalovirus infection; all except two were in initially seronegative subjects who received kidneys from seropositive donors. Primary infection and disease in nonimmune recipients may be caused by cytomegalovirus transmitted by the kidneys of latently infected seropositive donors."} {"id": "PMID:171568", "title": "Cell-mediated immunity to Epstein-Barr-virus-transformed lymphoblastoid cells in acute infectious mononucleosis.", "content": "Mononuclear peripheral blood leukocytes from 21 patients with infectious mononucleosis and 16 healthy controls were tested in a 51Cr-release assay for cytotoxicity against two human lymphoblastoid cell lines derived from the same donor. One line contained the Epstein-Barr virus (EBV); the other did not. Acute-phase leukocytes were significantly more cytotoxic against the EBV-infected cell line than were control leukocytes. Mean (+/- S.E.) lysis at a leukocyte-target-cell ratio of 100:1 was 10.6 +/- 1.6 per cent for patients and 3.4 +/- 0.6 per cent for controls (P less than 0.0005). Cytotoxicity correlated with the percentage of atypical lymphocytes. Cells of three patients with acute mononucleosis-like illnesses failed to show killing activity above those of normal controls. Cytotoxicity against the EBV-negative line was not significantly different for each group. The finding of cytotoxic cells in infectious-mononucleosis patients with atypical lymphocytes suggests that these cells operate in vivo to limit the proliferation of altered EBV-transformed B lymphoblasts.", "contents": "Cell-mediated immunity to Epstein-Barr-virus-transformed lymphoblastoid cells in acute infectious mononucleosis. Mononuclear peripheral blood leukocytes from 21 patients with infectious mononucleosis and 16 healthy controls were tested in a 51Cr-release assay for cytotoxicity against two human lymphoblastoid cell lines derived from the same donor. One line contained the Epstein-Barr virus (EBV); the other did not. Acute-phase leukocytes were significantly more cytotoxic against the EBV-infected cell line than were control leukocytes. Mean (+/- S.E.) lysis at a leukocyte-target-cell ratio of 100:1 was 10.6 +/- 1.6 per cent for patients and 3.4 +/- 0.6 per cent for controls (P less than 0.0005). Cytotoxicity correlated with the percentage of atypical lymphocytes. Cells of three patients with acute mononucleosis-like illnesses failed to show killing activity above those of normal controls. Cytotoxicity against the EBV-negative line was not significantly different for each group. The finding of cytotoxic cells in infectious-mononucleosis patients with atypical lymphocytes suggests that these cells operate in vivo to limit the proliferation of altered EBV-transformed B lymphoblasts."} {"id": "PMID:171569", "title": "Increased risk of endometrial carcinoma among users of conjugated estrogens.", "content": "The possibility that the use of conjugated estrogens increases the risk of endometrial carcinoma was investigated in patients and a twofold age-matched control series from the same population. Conjugated estrogens (principally sodium estrone sulfate) use was recorded for 57 per cent of 94 patients with endometrial carcinoma, and for 15 per cent of controls. The corresponding point estimate of the (instantaneous) risk ratio was 7.6 with a one-sided 95 per cent lower confidence limit of 4.7. The risk-ratio estimate increased with duration of exposure: from 5.6 for 1 to 4.9 years exposure to 13.9 for seven or more years. The estimated proportion of cases related to conjugated estrogens, the etiologic fraction, was 50 per cent with a one-sided 95 per cent lower confidence limit of 41 per cent. These data suggest that conjugated estrogens have an etiologic role in endometrial carcinoma.", "contents": "Increased risk of endometrial carcinoma among users of conjugated estrogens. The possibility that the use of conjugated estrogens increases the risk of endometrial carcinoma was investigated in patients and a twofold age-matched control series from the same population. Conjugated estrogens (principally sodium estrone sulfate) use was recorded for 57 per cent of 94 patients with endometrial carcinoma, and for 15 per cent of controls. The corresponding point estimate of the (instantaneous) risk ratio was 7.6 with a one-sided 95 per cent lower confidence limit of 4.7. The risk-ratio estimate increased with duration of exposure: from 5.6 for 1 to 4.9 years exposure to 13.9 for seven or more years. The estimated proportion of cases related to conjugated estrogens, the etiologic fraction, was 50 per cent with a one-sided 95 per cent lower confidence limit of 41 per cent. These data suggest that conjugated estrogens have an etiologic role in endometrial carcinoma."} {"id": "PMID:171573", "title": "HBs-Ag-negative hepatitis in a hemodialysis unit: relation to Epstein-Barr virus.", "content": "Eleven of 40 patients in a hemodialysis unit had clinical or biochemical evidence of hepatitis during a five-week period. The clinical disease was mild, being limited solely to dialysis patients. Epidemiologic investigation indicated that the incubation period was between 17 and 35 days and that 10 of 11 patients had been exposed to a single venous-pressure monitor before onset. Dried blood and evidence of blood reflux up the venous-pressure gauge suggested that cross-contamination of the blood of successive patients probably resulted in transmission of disease. No association with the hepatitis B surface antigen or anti-hepatitis B antibody was demonstrated, but 10 of the 11 patients with elevated transaminase levels had evidence of recent exposure, to Epstein-Barr virus as manifested either by Ox-cell hemolysin titers or rises in titers to viral capsid antigen.", "contents": "HBs-Ag-negative hepatitis in a hemodialysis unit: relation to Epstein-Barr virus. Eleven of 40 patients in a hemodialysis unit had clinical or biochemical evidence of hepatitis during a five-week period. The clinical disease was mild, being limited solely to dialysis patients. Epidemiologic investigation indicated that the incubation period was between 17 and 35 days and that 10 of 11 patients had been exposed to a single venous-pressure monitor before onset. Dried blood and evidence of blood reflux up the venous-pressure gauge suggested that cross-contamination of the blood of successive patients probably resulted in transmission of disease. No association with the hepatitis B surface antigen or anti-hepatitis B antibody was demonstrated, but 10 of the 11 patients with elevated transaminase levels had evidence of recent exposure, to Epstein-Barr virus as manifested either by Ox-cell hemolysin titers or rises in titers to viral capsid antigen."} {"id": "PMID:171574", "title": "Potentiation of hypoglycemic effect of sulfonylureas by halofenate.", "content": "We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes.", "contents": "Potentiation of hypoglycemic effect of sulfonylureas by halofenate. We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes."} {"id": "PMID:171575", "title": "Elevated histaminase (diamine oxidase) activity in small-cell carcinoma of the lung.", "content": "To investigate the possible embryologic relation between small-cell carcinoma of the lung and medullary thyroid carcinoma, we measured plasma histaminase (an enzyme found in medullary carcinoma tissue) in 25 patients with small-cell tumors. The assays used histamine and putrescine as substrates. Thirty-two per cent of the patients by the histamine assay, and 31 per cent by the putrescine, had values greater than +2 S.D. from the mean for 63 normal persons. In contrast, among 20 patients with squamous and large-cell lung tumors, one (by the histamine assay), and two (by the putrescine) had elevated values. In four of five autopsy cases, histaminase was high in small-cell carcinoma tissue. The enzyme in plasma and in tumor behaved as classic histaminase in substrate specificity, and in response to inhibitors. The data support the proposed embryologic relation between small-cell lung carcinoma and medullary thyroid carcinoma, and further associate histaminase with some neural crest tumors.", "contents": "Elevated histaminase (diamine oxidase) activity in small-cell carcinoma of the lung. To investigate the possible embryologic relation between small-cell carcinoma of the lung and medullary thyroid carcinoma, we measured plasma histaminase (an enzyme found in medullary carcinoma tissue) in 25 patients with small-cell tumors. The assays used histamine and putrescine as substrates. Thirty-two per cent of the patients by the histamine assay, and 31 per cent by the putrescine, had values greater than +2 S.D. from the mean for 63 normal persons. In contrast, among 20 patients with squamous and large-cell lung tumors, one (by the histamine assay), and two (by the putrescine) had elevated values. In four of five autopsy cases, histaminase was high in small-cell carcinoma tissue. The enzyme in plasma and in tumor behaved as classic histaminase in substrate specificity, and in response to inhibitors. The data support the proposed embryologic relation between small-cell lung carcinoma and medullary thyroid carcinoma, and further associate histaminase with some neural crest tumors."} {"id": "PMID:171576", "title": "Presence in normal human testes of a chorionic-gonadotropin-like substance distinct from human luteinizing hormone.", "content": "The high rate of human chorionic gonadotropin production by testicular tumors caused us to investigate the possibility that normal human testes contain small amounts of that substance. Extracts of human testes obtained at autopsy demonstrated parallel inhibition curves to the human chorionic gonadotropin standard in a radioimmunoassay specific for the hormone. The immunoreactive material was adsorbed onto concanavalin A, a reaction characteristic of glycoproteins, and was eluted within the chorionic gonadotropin range on Sephadex G-100 column chromatography. Solubilized receptor proteins for the hormone could not be identified in the extracts. The demonstration that the normal human testes contain a glycoprotein similar or identical to human chorionic gonadotropin suggests that the fetal genome responsible for production of the hormone during pregnancy is not completely suppressed in the adult. Excessive productton of this glycoprotein may account for the high levels of human chorionic gonadotropin reported in the serum of patients with germ-cell tumors of the testes.", "contents": "Presence in normal human testes of a chorionic-gonadotropin-like substance distinct from human luteinizing hormone. The high rate of human chorionic gonadotropin production by testicular tumors caused us to investigate the possibility that normal human testes contain small amounts of that substance. Extracts of human testes obtained at autopsy demonstrated parallel inhibition curves to the human chorionic gonadotropin standard in a radioimmunoassay specific for the hormone. The immunoreactive material was adsorbed onto concanavalin A, a reaction characteristic of glycoproteins, and was eluted within the chorionic gonadotropin range on Sephadex G-100 column chromatography. Solubilized receptor proteins for the hormone could not be identified in the extracts. The demonstration that the normal human testes contain a glycoprotein similar or identical to human chorionic gonadotropin suggests that the fetal genome responsible for production of the hormone during pregnancy is not completely suppressed in the adult. Excessive productton of this glycoprotein may account for the high levels of human chorionic gonadotropin reported in the serum of patients with germ-cell tumors of the testes."} {"id": "PMID:171577", "title": "Evidence for viral hepatitis other than type A or type B among persons in Costa Rica.", "content": "In studies of hepatitis in an endemic zone in Costa Rica, 103 patients were examined for antibodies against hepatitts A by the immune-adherence assay, for hepatitis B antigen and its antibody by radioimmunoassay and passive hemagglutination, respectively, and for antibodies against cytomegalovirus by complement fixation. Twelve cases were encountered in which both Type A and Type B hepatitis could be excluded on the basis of serologic testing. In all but one of these 12 patients, cytomegalovirus infection was also excluded. The patients had not had blood transfusions and available evidence pointed to person-to-person transmission. The illness in these patients was evidently neither hepatitis A nor hepatitis B and qualifies for consideration as the still hypothetical third type of hepatitis (\"C\"?).", "contents": "Evidence for viral hepatitis other than type A or type B among persons in Costa Rica. In studies of hepatitis in an endemic zone in Costa Rica, 103 patients were examined for antibodies against hepatitts A by the immune-adherence assay, for hepatitis B antigen and its antibody by radioimmunoassay and passive hemagglutination, respectively, and for antibodies against cytomegalovirus by complement fixation. Twelve cases were encountered in which both Type A and Type B hepatitis could be excluded on the basis of serologic testing. In all but one of these 12 patients, cytomegalovirus infection was also excluded. The patients had not had blood transfusions and available evidence pointed to person-to-person transmission. The illness in these patients was evidently neither hepatitis A nor hepatitis B and qualifies for consideration as the still hypothetical third type of hepatitis (\"C\"?)."} {"id": "PMID:171582", "title": "X-ray analysis of glucagon and its relationship to receptor binding.", "content": "X-ray analysis of the pancreatic hormone glucagon shows that in crystals the polypeptide adopts a mainly helical conformation, which is stabilised by hydrophobic interactions between molecules related by threefold symmetry. A model is presented in which the glucagon molecule exists in dilute solutions as an equilibrium population of conformers with little retention of conformers with little retention of structure, and in which the helical conformation is stablised by hydrophobic interactions either as an oligomer or as a complex with the receptor.", "contents": "X-ray analysis of glucagon and its relationship to receptor binding. X-ray analysis of the pancreatic hormone glucagon shows that in crystals the polypeptide adopts a mainly helical conformation, which is stabilised by hydrophobic interactions between molecules related by threefold symmetry. A model is presented in which the glucagon molecule exists in dilute solutions as an equilibrium population of conformers with little retention of conformers with little retention of structure, and in which the helical conformation is stablised by hydrophobic interactions either as an oligomer or as a complex with the receptor."} {"id": "PMID:171589", "title": "Mode of action of antirheumatic drugs on the cyclic 3',5'-AMP regulated glycosaminoglycan secretion in fibroblasts.", "content": "The effect non-steroidal anti-inflammatory drugs on formation and release of glycosaminoglycans (GAG) and cyclic 3',5'-AMP levels was studied in embryonic mouse fibroblasts. The results were compared and correlated with the action of these drugs on cyclic 3',5'-AMP-dependent as well as independent protein kinase obtained from bovine diaphragm. 1. Phenylbutazone dose-dependently decreased cyclic 3',5'-AMP levels and GAG secretion both in unstimulated and PGE1 stimulated cells. 2. Indometacin decreased cyclic 3',5'-AMP levels and GAG secretion only in cells with elevated cyclic 3',5'-AMP levels after stimulation by PGE1. 3. Sodium salicylate decreased cyclic 3',5'-AMP levels in the presence and absence of PGE1. However, GAG secretion was reduced only in cells with elevated cyclic 3',5'-AMP levels, since the drug activated cyclic 3',5'-AMP-independent protein kinase activity, thus presumably precluding changes in GAG formation at low levels of cyclic 3',5'-AMP. 4. Mefenamic acid decreased cyclic 3',5'-AMP levels in cells stimulated by PGE1, whereas GAG secretion was increased both in the absence and presence of PGE1. This increase in GAG secretion was closely correlated to an enhanced cyclic 3',5'-AMP-dependent and independent protein kinase activity. The results indicate that non-steroidal anti-inflammatory drugs may exert their effects on GAG formation by interfering with cyclic 3',-5'-AMP formation or function.", "contents": "Mode of action of antirheumatic drugs on the cyclic 3',5'-AMP regulated glycosaminoglycan secretion in fibroblasts. The effect non-steroidal anti-inflammatory drugs on formation and release of glycosaminoglycans (GAG) and cyclic 3',5'-AMP levels was studied in embryonic mouse fibroblasts. The results were compared and correlated with the action of these drugs on cyclic 3',5'-AMP-dependent as well as independent protein kinase obtained from bovine diaphragm. 1. Phenylbutazone dose-dependently decreased cyclic 3',5'-AMP levels and GAG secretion both in unstimulated and PGE1 stimulated cells. 2. Indometacin decreased cyclic 3',5'-AMP levels and GAG secretion only in cells with elevated cyclic 3',5'-AMP levels after stimulation by PGE1. 3. Sodium salicylate decreased cyclic 3',5'-AMP levels in the presence and absence of PGE1. However, GAG secretion was reduced only in cells with elevated cyclic 3',5'-AMP levels, since the drug activated cyclic 3',5'-AMP-independent protein kinase activity, thus presumably precluding changes in GAG formation at low levels of cyclic 3',5'-AMP. 4. Mefenamic acid decreased cyclic 3',5'-AMP levels in cells stimulated by PGE1, whereas GAG secretion was increased both in the absence and presence of PGE1. This increase in GAG secretion was closely correlated to an enhanced cyclic 3',5'-AMP-dependent and independent protein kinase activity. The results indicate that non-steroidal anti-inflammatory drugs may exert their effects on GAG formation by interfering with cyclic 3',-5'-AMP formation or function."} {"id": "PMID:171590", "title": "Bovine adrenal cortex adenylate cyclase: properties of the particulate enzyme and effects of guanyl nucleotides.", "content": "The preparation of a partially purified plasma membrane fraction from bovine adrenal cortex is described. Adenylate cyclase in this particulate preparation retained high sensitivity to ACTH and is also stimulated by 5'-guanylyl-imidodiphosphate [Gpp(NH)p]. GTP, in contrast to Gpp(NH)p, had very little intrinsic activity to stimulate activity to stimulate adenylate cyclase. GTP could however, with high affinity, inhibit the Gpp(NH)p effects on adenylate cyclase. When the concentration of creatine phosphate, a component of the ATP-regenerating system in the adenylate cyclase assay mixture, was lowered from 20 to 2 mM (at 0.1 mM ATP, 5 MM MG2+) GTP, dGTP and other nucleotides like ITP and much less UTP or CTP gained considerable intrinsic activity in the presence of ACTH to stimulate adenylate cyclase. The apparent affinities of the nucleotides for ACTH-stimulated adenylate cyclase from bovine adrenal cortex (at 2 mM creatine phosphate) were, GTP = dGTP greater than Gpp(NH)p greater than Gpp(CH2)p (5'-guanylyl-beta, gamma-methylene-diphosphonate) greater than ITP greater than UTP greater than CTP. These findings indicate that regulatory nucleotide binding sites exist for bovine adrenal cortex adenylate cyclase. Their specificity is similar to the nucleotide sites modulating angiotensin binding in bovine adrenal cortex plasma membranes (Glossmann et al., 1974a). The regulatory nucleotide binding sites for the adrenal cortex adenylate cyclase complex can also be identified under conditions where only Gpp(NH)p has high intrinsic activity (e.g. at 20 mM creatine phosphate) but other nucleotides like GTP act as antagonists. Both stimulants, ACTH and Gpp(NH)p, appear to remain firmly bound to the particulate membrane preparation, as suggested by preincubation experiments.", "contents": "Bovine adrenal cortex adenylate cyclase: properties of the particulate enzyme and effects of guanyl nucleotides. The preparation of a partially purified plasma membrane fraction from bovine adrenal cortex is described. Adenylate cyclase in this particulate preparation retained high sensitivity to ACTH and is also stimulated by 5'-guanylyl-imidodiphosphate [Gpp(NH)p]. GTP, in contrast to Gpp(NH)p, had very little intrinsic activity to stimulate activity to stimulate adenylate cyclase. GTP could however, with high affinity, inhibit the Gpp(NH)p effects on adenylate cyclase. When the concentration of creatine phosphate, a component of the ATP-regenerating system in the adenylate cyclase assay mixture, was lowered from 20 to 2 mM (at 0.1 mM ATP, 5 MM MG2+) GTP, dGTP and other nucleotides like ITP and much less UTP or CTP gained considerable intrinsic activity in the presence of ACTH to stimulate adenylate cyclase. The apparent affinities of the nucleotides for ACTH-stimulated adenylate cyclase from bovine adrenal cortex (at 2 mM creatine phosphate) were, GTP = dGTP greater than Gpp(NH)p greater than Gpp(CH2)p (5'-guanylyl-beta, gamma-methylene-diphosphonate) greater than ITP greater than UTP greater than CTP. These findings indicate that regulatory nucleotide binding sites exist for bovine adrenal cortex adenylate cyclase. Their specificity is similar to the nucleotide sites modulating angiotensin binding in bovine adrenal cortex plasma membranes (Glossmann et al., 1974a). The regulatory nucleotide binding sites for the adrenal cortex adenylate cyclase complex can also be identified under conditions where only Gpp(NH)p has high intrinsic activity (e.g. at 20 mM creatine phosphate) but other nucleotides like GTP act as antagonists. Both stimulants, ACTH and Gpp(NH)p, appear to remain firmly bound to the particulate membrane preparation, as suggested by preincubation experiments."} {"id": "PMID:171591", "title": "Chloramphenicol/thiamphenicol and cycloheximide as tools for the measurement of mitochondrial protein synthesis in vitro during organogenesis of rat embryos.", "content": "1. A test system was developed to allow the measurement of protein synthesis in vitro in mitochondria from tissues which were accessible only in small quantities. The subcellular fractions which could be isolated are not purely mitochondrial but contain other particles as well, mainly microsomal, which are also active in protein synthesis. The following differences between mitochondrial and microsomal protein synthesis in vitro were used to measure selectively the mitochondrial portion in cell fractions sedimenting between 600 and 10000 X g: selective inhibition of mitochondrial protein synthesis by chloramphenicol/thiamphenicol selective inhibition of microsomal protein synthesis by cycloheximide kinetics of amino acid incorporation a medium favoring mitochondrial protein synthesis Activity of mitochondrial protein synthesis was based on measurements of cytochrome oxidase, a mitochondrial marker enzyme. 2. The technique developed was used for the evaluation of mitochondrial protein synthesis in mammalian embryonic tissues. It may equally well be applied to other tissues available in small amounts and in cases where the isolation of highly purified mitochondrial fractions is met with difficulty. 3. Comparing the rate of 14C-phenylalanine incorporation into mitochondrial protein from rat embryos at different stages of gestation, it was found that mitochondria from 11=day-old rat embryos exhibit an approximately 30-fold higher capacity for protein synthesis than those of day 13-16. On day 12 the capacity is 6 times higher than on the following days.", "contents": "Chloramphenicol/thiamphenicol and cycloheximide as tools for the measurement of mitochondrial protein synthesis in vitro during organogenesis of rat embryos. 1. A test system was developed to allow the measurement of protein synthesis in vitro in mitochondria from tissues which were accessible only in small quantities. The subcellular fractions which could be isolated are not purely mitochondrial but contain other particles as well, mainly microsomal, which are also active in protein synthesis. The following differences between mitochondrial and microsomal protein synthesis in vitro were used to measure selectively the mitochondrial portion in cell fractions sedimenting between 600 and 10000 X g: selective inhibition of mitochondrial protein synthesis by chloramphenicol/thiamphenicol selective inhibition of microsomal protein synthesis by cycloheximide kinetics of amino acid incorporation a medium favoring mitochondrial protein synthesis Activity of mitochondrial protein synthesis was based on measurements of cytochrome oxidase, a mitochondrial marker enzyme. 2. The technique developed was used for the evaluation of mitochondrial protein synthesis in mammalian embryonic tissues. It may equally well be applied to other tissues available in small amounts and in cases where the isolation of highly purified mitochondrial fractions is met with difficulty. 3. Comparing the rate of 14C-phenylalanine incorporation into mitochondrial protein from rat embryos at different stages of gestation, it was found that mitochondria from 11=day-old rat embryos exhibit an approximately 30-fold higher capacity for protein synthesis than those of day 13-16. On day 12 the capacity is 6 times higher than on the following days."} {"id": "PMID:171592", "title": "Embryonic development and mitochondrial function. 1. Effects of chloramphenicol infusion on the synthesis of cytochrome oxidase and DNA in rat embryos during late organogenesis.", "content": "Cytochrome oxidase, which is partially synthesized by the mitochondrion, was used as a measure for the development of mitochondrial function in rat embryos during the late stage of organogenesis. For this purpose the specific inhibitor of mitochondrial protein synthesis, chloramphenicol (CAP), served as a tool. Due to the rapid elimination rate of CAP from rats, a method for continuous infusion which would not cause immobilization to the animals was devised. 1. Pharmacokinetic studies proved that CAP reaches the embryo before placentation. Concentrations of CAP in the embryo are as high as they are in the maternal serum (about 20 mug/ml serum or g embryo) and thuse are sufficiently in supply for the inhibition of mitochondrial proteins synthesis, if 1000 mg/kg CAP are infused intravenously per 24 hrs. CAP is partially excluded from the embryonic compartment after the placental barrier has fully developed: whereas CAP concentration in the maternal serum remains at about 20 mug/ml, the concentration in the embryonic compartment drops to about 10 mug/g embryonic tissue during day 13 of gestation. 2. The average cytochrome oxidase activity per cell is very low (about 1 nmole O2/min X mug DNA-1) in embryonic tissue as it is in many other rapidly proliferating tissues. It is 15-60 times higher in slowly proliferating tissues, as, for example, the adult rat liver or brain (greater than 14 nmoles O2/min X mug DNA-1). 3. When the infusion technique is applied on day 12 of gestation, a sufficiently high concentration of CAP in embryonic tissue can be obtained to inhibit the synthesis of cytochrome oxidase. In constrast to tissues of an adult organism-as in the case of liver after partial hepatectomy- in embryonic tissues this limitation in the availablity of cytochrome oxidase appearently results in a critical reduction of energy production, which subsequently affects the DNA synthesis and embryonic growth. 4. The possible relevance and applicability of these experimental findings to man is discussed.", "contents": "Embryonic development and mitochondrial function. 1. Effects of chloramphenicol infusion on the synthesis of cytochrome oxidase and DNA in rat embryos during late organogenesis. Cytochrome oxidase, which is partially synthesized by the mitochondrion, was used as a measure for the development of mitochondrial function in rat embryos during the late stage of organogenesis. For this purpose the specific inhibitor of mitochondrial protein synthesis, chloramphenicol (CAP), served as a tool. Due to the rapid elimination rate of CAP from rats, a method for continuous infusion which would not cause immobilization to the animals was devised. 1. Pharmacokinetic studies proved that CAP reaches the embryo before placentation. Concentrations of CAP in the embryo are as high as they are in the maternal serum (about 20 mug/ml serum or g embryo) and thuse are sufficiently in supply for the inhibition of mitochondrial proteins synthesis, if 1000 mg/kg CAP are infused intravenously per 24 hrs. CAP is partially excluded from the embryonic compartment after the placental barrier has fully developed: whereas CAP concentration in the maternal serum remains at about 20 mug/ml, the concentration in the embryonic compartment drops to about 10 mug/g embryonic tissue during day 13 of gestation. 2. The average cytochrome oxidase activity per cell is very low (about 1 nmole O2/min X mug DNA-1) in embryonic tissue as it is in many other rapidly proliferating tissues. It is 15-60 times higher in slowly proliferating tissues, as, for example, the adult rat liver or brain (greater than 14 nmoles O2/min X mug DNA-1). 3. When the infusion technique is applied on day 12 of gestation, a sufficiently high concentration of CAP in embryonic tissue can be obtained to inhibit the synthesis of cytochrome oxidase. In constrast to tissues of an adult organism-as in the case of liver after partial hepatectomy- in embryonic tissues this limitation in the availablity of cytochrome oxidase appearently results in a critical reduction of energy production, which subsequently affects the DNA synthesis and embryonic growth. 4. The possible relevance and applicability of these experimental findings to man is discussed."} {"id": "PMID:171597", "title": "Time-course of the effect of alpha-methyl-p-tyrosine on ACTH secretion.", "content": "250 mg/kg i.p. of the methyl ester of alpha-methyl-p-tyrosine (alpha-MpT) produced a rapid increase (by 1 h) in immunoreactive plasma ACTH, whereas the hypothalamic norepinephrine (NE) concentration and plasma corticosterone (B) changed significantly only 6 h after the administration of the inhibitor. These data suggest that the norepinephrinergic inhibitory tonus of CRF-ACTH secretion depends on the availability of a rapidly utilized pool of transmitter, affected in a very short time by alpha-MpT.", "contents": "Time-course of the effect of alpha-methyl-p-tyrosine on ACTH secretion. 250 mg/kg i.p. of the methyl ester of alpha-methyl-p-tyrosine (alpha-MpT) produced a rapid increase (by 1 h) in immunoreactive plasma ACTH, whereas the hypothalamic norepinephrine (NE) concentration and plasma corticosterone (B) changed significantly only 6 h after the administration of the inhibitor. These data suggest that the norepinephrinergic inhibitory tonus of CRF-ACTH secretion depends on the availability of a rapidly utilized pool of transmitter, affected in a very short time by alpha-MpT."} {"id": "PMID:171598", "title": "Cortical and subcortical projected foci in cats: inhibitory action of taurine.", "content": "The effects of local application of taurine and isethionic acid on the propagation of the epileptic activity to the mirror area in cats have been studied. Cortical and amygdaloid acute foci were induced by local administration of conjugated estrogens. Taurine proved to be effective in reducing and sometimes in abolishing the appearance of the epileptic propagated elements in the mirror area. When this agent was applied 30 minutes before the induction of the primary focus, the single spike transmission was reduced or prevented; however, the transmission of a seizure was not blocked. No changes in the transmitted phenomena were observed when isethionic acid was administered with the same technique as that used for taurine. The present study stresses the clear antiepileptic activity of taurine in this experimental model, ruling out the possibility of an unspecific interaction with the epileptogenic agents. Moreover, it is suggested that the deamination of taurine is not important for its antiepileptic action.", "contents": "Cortical and subcortical projected foci in cats: inhibitory action of taurine. The effects of local application of taurine and isethionic acid on the propagation of the epileptic activity to the mirror area in cats have been studied. Cortical and amygdaloid acute foci were induced by local administration of conjugated estrogens. Taurine proved to be effective in reducing and sometimes in abolishing the appearance of the epileptic propagated elements in the mirror area. When this agent was applied 30 minutes before the induction of the primary focus, the single spike transmission was reduced or prevented; however, the transmission of a seizure was not blocked. No changes in the transmitted phenomena were observed when isethionic acid was administered with the same technique as that used for taurine. The present study stresses the clear antiepileptic activity of taurine in this experimental model, ruling out the possibility of an unspecific interaction with the epileptogenic agents. Moreover, it is suggested that the deamination of taurine is not important for its antiepileptic action."} {"id": "PMID:171599", "title": "Nuclear bodies in Creutzfeldt-Jakob and Alzheimer's diseases.", "content": "Nuclear bodies types I, II, III, and IV, as described by Bouteille, Kalifat, and Delarue, have been found in one case of Creutzfeldt-Jakob disease and one case of Alzheimer's disease. The relationship of nuclear bodies to viral disease in the central nervous system is not clear.", "contents": "Nuclear bodies in Creutzfeldt-Jakob and Alzheimer's diseases. Nuclear bodies types I, II, III, and IV, as described by Bouteille, Kalifat, and Delarue, have been found in one case of Creutzfeldt-Jakob disease and one case of Alzheimer's disease. The relationship of nuclear bodies to viral disease in the central nervous system is not clear."} {"id": "PMID:171596", "title": "[Muscle cell structure in polymyositis].", "content": "Electron microscopic investigations of muscles from patients with chronic polymyositis demonstrated presence of cytoplasmatic, tubular structures and extracellular virus-like particles. Their size, morphology and location suggest multiplication of viruses from the group of parainfluenza viruses within the muscle cell in \"infected\" cultures of human fetal muscles. Beside viruses belonging to the parainfluenza group presence of viruses from the herpes group was demonstrated. The latter belong to latent viruses.", "contents": "[Muscle cell structure in polymyositis]. Electron microscopic investigations of muscles from patients with chronic polymyositis demonstrated presence of cytoplasmatic, tubular structures and extracellular virus-like particles. Their size, morphology and location suggest multiplication of viruses from the group of parainfluenza viruses within the muscle cell in \"infected\" cultures of human fetal muscles. Beside viruses belonging to the parainfluenza group presence of viruses from the herpes group was demonstrated. The latter belong to latent viruses."} {"id": "PMID:171602", "title": "[Case of pseudopseudohypoparathyroidism].", "content": "A case of pseudo-pseudo-parathyroidism, in which normal blood chemistry data were accompanied by marked shortening of the 4th metacarpus and metatarsus, and a suggestion of syndactyly, is reported.", "contents": "[Case of pseudopseudohypoparathyroidism]. A case of pseudo-pseudo-parathyroidism, in which normal blood chemistry data were accompanied by marked shortening of the 4th metacarpus and metatarsus, and a suggestion of syndactyly, is reported."} {"id": "PMID:171605", "title": "Electron microscopy of Cowdria ruminantium infected reticulo-endothelial cells of the mammalian host.", "content": "An electron microscopic study of structures suspected to represent a possible developmental cycle of Cowdria ruminantium in reticulo-endothelial cells of mice and ruminants is reported. After infection dense bodies increase in size and undergo division to form fragmented dense bodies. These in turn apparently sub-divide and become organized to give rise to mature \"organisms\". In none of these structures do limiting membranes separate the parasitic inclusions from the host cell cytoplasm. Present observations suggest that growth of the organism in reticulo-endothelial cells differs from that of chlamydial and rickettsial agents and somewhat resembles the replication of some viruses. Developmental stages observed after infection of ruminants with the Ball 3 strain of the heartwater agent are indistinguishable from those seen with the mouse adapted strain. These observations support the hypothesis that C. ruminantium released from reticulo-endothelial cells subsequently penetrates endothelial cells where further multiplication by binary fission occurs.", "contents": "Electron microscopy of Cowdria ruminantium infected reticulo-endothelial cells of the mammalian host. An electron microscopic study of structures suspected to represent a possible developmental cycle of Cowdria ruminantium in reticulo-endothelial cells of mice and ruminants is reported. After infection dense bodies increase in size and undergo division to form fragmented dense bodies. These in turn apparently sub-divide and become organized to give rise to mature \"organisms\". In none of these structures do limiting membranes separate the parasitic inclusions from the host cell cytoplasm. Present observations suggest that growth of the organism in reticulo-endothelial cells differs from that of chlamydial and rickettsial agents and somewhat resembles the replication of some viruses. Developmental stages observed after infection of ruminants with the Ball 3 strain of the heartwater agent are indistinguishable from those seen with the mouse adapted strain. These observations support the hypothesis that C. ruminantium released from reticulo-endothelial cells subsequently penetrates endothelial cells where further multiplication by binary fission occurs."} {"id": "PMID:171606", "title": "Effect of Clostridium perfringens epsilon toxin on the blood brain barrier of mice.", "content": "It was shown that Clostridium perfringens epsilon toxin has the effect of allowing the passage of 125I polyvinyl-pyrrolidone and 125I human serum albumin into mouse brain. These substances did not enter the brains of normal control mice. The passage of albumin into the brains of mice poisoned with epsilon toxin was extremely rapid. When large doses of toxin (+/-4 000 MLD) were given death ensued within 2-3 min at which stage 1,5% of the injected albumin had already entered the brain. In cases where smaller doses were given and the time interval between injection and death was longer the figure was increased to 2-2 1/2% of the injected plasma albumin.", "contents": "Effect of Clostridium perfringens epsilon toxin on the blood brain barrier of mice. It was shown that Clostridium perfringens epsilon toxin has the effect of allowing the passage of 125I polyvinyl-pyrrolidone and 125I human serum albumin into mouse brain. These substances did not enter the brains of normal control mice. The passage of albumin into the brains of mice poisoned with epsilon toxin was extremely rapid. When large doses of toxin (+/-4 000 MLD) were given death ensued within 2-3 min at which stage 1,5% of the injected albumin had already entered the brain. In cases where smaller doses were given and the time interval between injection and death was longer the figure was increased to 2-2 1/2% of the injected plasma albumin."} {"id": "PMID:171607", "title": "Occurrence of juvenile angiofibroma in middle age.", "content": "A case of juvenile angiofibroma occurring in a male patient of 49 years is described. Histopathology and oncogenesis are discussed.", "contents": "Occurrence of juvenile angiofibroma in middle age. A case of juvenile angiofibroma occurring in a male patient of 49 years is described. Histopathology and oncogenesis are discussed."} {"id": "PMID:171608", "title": "Asymmetric adsorption by quartz: a model for the prebiotic origin of optical activity.", "content": "One mechanism previously proposed for the abiotic accumulation of molecules of one chirality in nature is asymmetric adsorption on the chiral surfaces of optically active quartz crystals. Earlier literature in this field is reviewed, with the conclusion that previous investigations of this phenomenon, using optical rotation criteria, have afforded ambiguous results. We now have studied the adsorption of radioactive D- and L-alanine on powdered d- and l-quartz, using change in radioactivity level as a criterion for both gross and differential adsorption. d-Quartz preferentially adsorbed D-alanine from anhydrous dimethyl-formamide solution, and l-quartz L-alanine. The differential adsorption varied between 1.0 and 1.8%. The implications of these observations are discussed from the viewpoint of early chemical evolution and the origin of optically active organic compounds in nature.", "contents": "Asymmetric adsorption by quartz: a model for the prebiotic origin of optical activity. One mechanism previously proposed for the abiotic accumulation of molecules of one chirality in nature is asymmetric adsorption on the chiral surfaces of optically active quartz crystals. Earlier literature in this field is reviewed, with the conclusion that previous investigations of this phenomenon, using optical rotation criteria, have afforded ambiguous results. We now have studied the adsorption of radioactive D- and L-alanine on powdered d- and l-quartz, using change in radioactivity level as a criterion for both gross and differential adsorption. d-Quartz preferentially adsorbed D-alanine from anhydrous dimethyl-formamide solution, and l-quartz L-alanine. The differential adsorption varied between 1.0 and 1.8%. The implications of these observations are discussed from the viewpoint of early chemical evolution and the origin of optically active organic compounds in nature."} {"id": "PMID:171609", "title": "Synthesis of biological molecules on molecular sieves.", "content": "Catalytic properties of aluminosilicates may play a role in the synthesis of biological molecules from simple gaseous molecules commonly found in planetary atmospheres. Urea, amino acids and UV absorbing substances have been obtained by heating CO and NH3 with Linde molecular sieves saturated with Ca+2, NH4+ or Fe+3. The yields of amino acids produced have been determined by an amino acid analyzer. The quantity of urea produced largely depends on the nature of the saturating cation. Experiments using 14CO confirm that the amino acids are not due to contaminants adsorbed on the surface of the molecular sieves.", "contents": "Synthesis of biological molecules on molecular sieves. Catalytic properties of aluminosilicates may play a role in the synthesis of biological molecules from simple gaseous molecules commonly found in planetary atmospheres. Urea, amino acids and UV absorbing substances have been obtained by heating CO and NH3 with Linde molecular sieves saturated with Ca+2, NH4+ or Fe+3. The yields of amino acids produced have been determined by an amino acid analyzer. The quantity of urea produced largely depends on the nature of the saturating cation. Experiments using 14CO confirm that the amino acids are not due to contaminants adsorbed on the surface of the molecular sieves."} {"id": "PMID:171610", "title": "Ultrastructural aspects of the thyroid in a case of human congenital goitre with cretinism.", "content": "Transmission electron microscope and scanning electron microscope studies in a case of congenital goitre associated with cretinism revealed the existence of two cell types: the first with rounded endoplasmic cisternae and normal lysosomes; the second characterized by an abundance of lysosomes and/or lipofuscin granules. Intermediary aspects suggested that the second cell type was the progeny of the first type. As colloid droplets and apical pseudopods engulfing colloid were nearly absent, and as NBE127I was elevated in the plasma, it is suggested that iodoprotein secretion occurred by a process different from colloid phagocytosis as observed after acute TSH stimulation.", "contents": "Ultrastructural aspects of the thyroid in a case of human congenital goitre with cretinism. Transmission electron microscope and scanning electron microscope studies in a case of congenital goitre associated with cretinism revealed the existence of two cell types: the first with rounded endoplasmic cisternae and normal lysosomes; the second characterized by an abundance of lysosomes and/or lipofuscin granules. Intermediary aspects suggested that the second cell type was the progeny of the first type. As colloid droplets and apical pseudopods engulfing colloid were nearly absent, and as NBE127I was elevated in the plasma, it is suggested that iodoprotein secretion occurred by a process different from colloid phagocytosis as observed after acute TSH stimulation."} {"id": "PMID:171611", "title": "Colchicine-induced lesions in the rat duodenum.", "content": "In rats subcutaneous injection of colchicine resulted in sub-cellular necrosis within the rapidly proliferating cells in the duodenal mucosa. Similar lesions resulted from the administration of cytosine arabinoside hydrochloride and the effects of both drugs were ameliorated by treatment with cycloheximide. It is suggested that these lesions are a form of shrinkage necrosis involved in the deletion of growing stem-cells which, in the absence of mitotic division, results in mucosal atrophy.", "contents": "Colchicine-induced lesions in the rat duodenum. In rats subcutaneous injection of colchicine resulted in sub-cellular necrosis within the rapidly proliferating cells in the duodenal mucosa. Similar lesions resulted from the administration of cytosine arabinoside hydrochloride and the effects of both drugs were ameliorated by treatment with cycloheximide. It is suggested that these lesions are a form of shrinkage necrosis involved in the deletion of growing stem-cells which, in the absence of mitotic division, results in mucosal atrophy."} {"id": "PMID:171612", "title": "Failure to induce autoimmune phenomena in mice by administration of highly purified C-type particles from NZB mice.", "content": "Highly purified C-type particles from milk of NZB mice were ineffective in the transfer of Coombs positive hemolytic anemia and cryoglobulinemia to neonatal BALB/cHeA and NZC/B1 mice. Injection of neonatal NZB mice with these particles did not change the frequency or time of onset of these phenomena. Antinuclear antibodies were found in all injected animals in the same frequencies as in the control groups.", "contents": "Failure to induce autoimmune phenomena in mice by administration of highly purified C-type particles from NZB mice. Highly purified C-type particles from milk of NZB mice were ineffective in the transfer of Coombs positive hemolytic anemia and cryoglobulinemia to neonatal BALB/cHeA and NZC/B1 mice. Injection of neonatal NZB mice with these particles did not change the frequency or time of onset of these phenomena. Antinuclear antibodies were found in all injected animals in the same frequencies as in the control groups."} {"id": "PMID:171615", "title": "Pulmonary pressure- volume relationships after corticotropin (ACTH) and salin injections in fetal rabbits.", "content": "ACTH mixed with barium sulfate injected into fetal rabbits on day 24 of a 31-day gestation was associated with increased lung maturity compared with lungs of noninjected controls when assessed by deflation pressure-volume curves and lung weight to body weight ratios measured on day 27. Fetuses injected with saline and barium sulfate also had accelerated (although somewhat less) lung maturation, perhaps from an ACTH-mediated response to stress. The ACTH group LA) maintained the largest lung volumes on deflation, followed by the saline group (B), the ACTH controls (C), and the saline controls (D). Volumes (percentage of total lung capacity) between the two injected groups and their controls (A versus C; B versus D) were significantly different at transthoracic pressures of 15, 10, 7, 4, 0, and -2 cm water (p less than 0.05). Volumes (percentage of total lung capacity) between the ACTH group and the saline group (A versus B) and between the two controls groups (C versus D) were not significantly different. Wet lung weight to body weight ratios were significantly different between the injected groups and their respective controls, between the two injected groups, and between the two control groups.", "contents": "Pulmonary pressure- volume relationships after corticotropin (ACTH) and salin injections in fetal rabbits. ACTH mixed with barium sulfate injected into fetal rabbits on day 24 of a 31-day gestation was associated with increased lung maturity compared with lungs of noninjected controls when assessed by deflation pressure-volume curves and lung weight to body weight ratios measured on day 27. Fetuses injected with saline and barium sulfate also had accelerated (although somewhat less) lung maturation, perhaps from an ACTH-mediated response to stress. The ACTH group LA) maintained the largest lung volumes on deflation, followed by the saline group (B), the ACTH controls (C), and the saline controls (D). Volumes (percentage of total lung capacity) between the two injected groups and their controls (A versus C; B versus D) were significantly different at transthoracic pressures of 15, 10, 7, 4, 0, and -2 cm water (p less than 0.05). Volumes (percentage of total lung capacity) between the ACTH group and the saline group (A versus B) and between the two controls groups (C versus D) were not significantly different. Wet lung weight to body weight ratios were significantly different between the injected groups and their respective controls, between the two injected groups, and between the two control groups."} {"id": "PMID:171616", "title": "Elevated urinary testosterone and androstanediol in precocious adrenarche.", "content": "Using a newly devised radioligand method for the simultaneous determination of urinary testosterone (T) and androstanediol (Adiol) nine girls with precocious adrenarche were evaluated. In the base-line state average urinary T excretion (1.29 mug/24 hr) and Adiol excretion (1.33 mug/24 hr) were significantly elevated when compared with 15 age-matched controls (0.3 and 0.33 mug/ 24 hr, respectively, P less than 0.001 for both). Adrenocorticotropic hormone (ACTH) infusion performed in five patients with precocious adrenarche produced at least a 50 greater than increase in urinary T excretion in all and a similar increase in Adiol excretion in four of five patients. Dexamethasone administration in the same five patients produced a 25 greater than fall in urinary T excretion in all and a comparable fall in Adiol in four.", "contents": "Elevated urinary testosterone and androstanediol in precocious adrenarche. Using a newly devised radioligand method for the simultaneous determination of urinary testosterone (T) and androstanediol (Adiol) nine girls with precocious adrenarche were evaluated. In the base-line state average urinary T excretion (1.29 mug/24 hr) and Adiol excretion (1.33 mug/24 hr) were significantly elevated when compared with 15 age-matched controls (0.3 and 0.33 mug/ 24 hr, respectively, P less than 0.001 for both). Adrenocorticotropic hormone (ACTH) infusion performed in five patients with precocious adrenarche produced at least a 50 greater than increase in urinary T excretion in all and a similar increase in Adiol excretion in four of five patients. Dexamethasone administration in the same five patients produced a 25 greater than fall in urinary T excretion in all and a comparable fall in Adiol in four."} {"id": "PMID:171617", "title": "Glucose production in the newborn dog. II. Evaluation of autonomic and enzymatic control in the isolated perfused canine liver.", "content": "The effects of birth and morepinephrine on hepatic glucose production, glycogenolysis, and gluconeogenesis were examined in livers isolated from fetal dogs at term, littermates 3 hr after delivery, and newborn dogs 1-5 days old. Livers were perfused in pairs with medium containing (6-3H)glucose (6 mM) and (3-14C)lactate (10 mM +/- a pharmacologic amount of norepinephrine (10(-6)M). Changes in glucose production rates were correlated with changes in the enzymatic activities controlling gluconeogenesis. Net glucose production was less than 0.48 mumol/min-g liver both fetal and 3 hr liver but stablized above 1 mumol/min-g later during the first day. Initially, mobilization of the fetal hepatic glycogen accounted for glucose output. Subsequently, incorporation of lactate into glucose rose from negligible fetal rates to 0.19 mumol/min-g and accounted for 21% of net glucose production on day 3. Mazimal pyruvate carboxylase activity and mitochondrial CO2 fixation increased postnatally and correlated directly with net glucose production, glucose production from glycogen, and glucose production from lactate. Fetal liver did not respond to norepinephrine. Thereafter, norepinephrine increase hepatic glucose production by stimulating glycogen breakdown. Postnatal acceleration of glucose production and the response to norepinephrine occurred only after indiction of mitochondrial CO3 fixation. During day 1 the decline of hepatic glycogen in response to norepinephrine correlated with both CO2 fixation and lactate incorporation into glucose. Thus, initiation of gluconegenesis after birth may have been required for the postnatal acceration of hepatic glucose production and for the regulation of glycogenolysis by norpinephrine.", "contents": "Glucose production in the newborn dog. II. Evaluation of autonomic and enzymatic control in the isolated perfused canine liver. The effects of birth and morepinephrine on hepatic glucose production, glycogenolysis, and gluconeogenesis were examined in livers isolated from fetal dogs at term, littermates 3 hr after delivery, and newborn dogs 1-5 days old. Livers were perfused in pairs with medium containing (6-3H)glucose (6 mM) and (3-14C)lactate (10 mM +/- a pharmacologic amount of norepinephrine (10(-6)M). Changes in glucose production rates were correlated with changes in the enzymatic activities controlling gluconeogenesis. Net glucose production was less than 0.48 mumol/min-g liver both fetal and 3 hr liver but stablized above 1 mumol/min-g later during the first day. Initially, mobilization of the fetal hepatic glycogen accounted for glucose output. Subsequently, incorporation of lactate into glucose rose from negligible fetal rates to 0.19 mumol/min-g and accounted for 21% of net glucose production on day 3. Mazimal pyruvate carboxylase activity and mitochondrial CO2 fixation increased postnatally and correlated directly with net glucose production, glucose production from glycogen, and glucose production from lactate. Fetal liver did not respond to norepinephrine. Thereafter, norepinephrine increase hepatic glucose production by stimulating glycogen breakdown. Postnatal acceleration of glucose production and the response to norepinephrine occurred only after indiction of mitochondrial CO3 fixation. During day 1 the decline of hepatic glycogen in response to norepinephrine correlated with both CO2 fixation and lactate incorporation into glucose. Thus, initiation of gluconegenesis after birth may have been required for the postnatal acceration of hepatic glucose production and for the regulation of glycogenolysis by norpinephrine."} {"id": "PMID:171618", "title": "Abnormalities of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of patients with Reye's syndrome.", "content": "Urea cycle function was evaluated in liver obtained from six patients with Reye's syndrome and from five control subjects. Reye's syndrome patients demonstrated normal activities for the extramitochondrial portion of the urea cycle, but showed marked abnormalities of the mitochondrial enzymes, i.e., carbamyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC) (Tables 2,3). CPS activity was reduced to less than 15% of control values in all four patients from whom tissues was obtained during the first 72 hr after the onset of encephalopathy. Two patents from whom tissue was not obtained until after 9 days of symptoms showed no reduction in CPS activity. The OTC activity was also reduced (3-67% of control values) in the four patients from whom tissue was obtained early in the illness. In addition, greater than 60% reduction in Vmax and Km for carbamyl phosphate was noted in all four patients in whom sample size permitted kinetic analysis, including both patients in whom CPS and OTC activity were not markedly reduced. The same kinetic abnormality as well as decreased CPS activity were experimentally produced in normal rate liver incubated in the presence of 1.0 mM 4-pentenoic acid, a short chain fatty acid and known hepatic mitochondrial toxin (Table 4).", "contents": "Abnormalities of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of patients with Reye's syndrome. Urea cycle function was evaluated in liver obtained from six patients with Reye's syndrome and from five control subjects. Reye's syndrome patients demonstrated normal activities for the extramitochondrial portion of the urea cycle, but showed marked abnormalities of the mitochondrial enzymes, i.e., carbamyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC) (Tables 2,3). CPS activity was reduced to less than 15% of control values in all four patients from whom tissues was obtained during the first 72 hr after the onset of encephalopathy. Two patents from whom tissue was not obtained until after 9 days of symptoms showed no reduction in CPS activity. The OTC activity was also reduced (3-67% of control values) in the four patients from whom tissue was obtained early in the illness. In addition, greater than 60% reduction in Vmax and Km for carbamyl phosphate was noted in all four patients in whom sample size permitted kinetic analysis, including both patients in whom CPS and OTC activity were not markedly reduced. The same kinetic abnormality as well as decreased CPS activity were experimentally produced in normal rate liver incubated in the presence of 1.0 mM 4-pentenoic acid, a short chain fatty acid and known hepatic mitochondrial toxin (Table 4)."} {"id": "PMID:171619", "title": "Longitudinal sleep patterns during pubertal growth: four-year follow up.", "content": "There were little or no indications of differences in sleep outcomes between the sexes. Results indicate a disturbance of sleep on initial laboratory nights relative to later nights. The results reported here clearly document the persistence of these effects from year to year. For the most part, sleep characteristics during the 4 years immediately after onset of puberty appear to represent a typical phase in the gradual patterns of changes across all ages. Total sleep time decreased markedly from 560 min in age range 10-12 to 424 min in age range 20-29, with our puberty subjects as intermediate levels. Puberty subjects has an average of 2.5 awakenings/night in the first 2 years as compared with 1.2/night in the last 2 years. The number of sleep stage shifts during the night varied around a constant mean value of approximately 37/night throughout all ages. The number of rapid eye movement (REM) period during the night decreased sharply for individuals from childhood (6.9/night) through adolescence (4.0/night), remaining constant thereafter. Percentages of the various sleep stages were fairly constant for individuals from age range 10-12 through age 30-39. Our puberty subjects had percentage profiles in near perfect agreement with the normal ontogenetic process. Normative data suggest that slow wave sleep reaches a peak at some point during the teen years.", "contents": "Longitudinal sleep patterns during pubertal growth: four-year follow up. There were little or no indications of differences in sleep outcomes between the sexes. Results indicate a disturbance of sleep on initial laboratory nights relative to later nights. The results reported here clearly document the persistence of these effects from year to year. For the most part, sleep characteristics during the 4 years immediately after onset of puberty appear to represent a typical phase in the gradual patterns of changes across all ages. Total sleep time decreased markedly from 560 min in age range 10-12 to 424 min in age range 20-29, with our puberty subjects as intermediate levels. Puberty subjects has an average of 2.5 awakenings/night in the first 2 years as compared with 1.2/night in the last 2 years. The number of sleep stage shifts during the night varied around a constant mean value of approximately 37/night throughout all ages. The number of rapid eye movement (REM) period during the night decreased sharply for individuals from childhood (6.9/night) through adolescence (4.0/night), remaining constant thereafter. Percentages of the various sleep stages were fairly constant for individuals from age range 10-12 through age 30-39. Our puberty subjects had percentage profiles in near perfect agreement with the normal ontogenetic process. Normative data suggest that slow wave sleep reaches a peak at some point during the teen years."} {"id": "PMID:171621", "title": "Solubility of various inert gases in rat skeletal muscle.", "content": "For the determination of solubility coefficients, isolated rat abdominal muscles were equilibrated at 37 degrees C with various inert gases saturated with water vapor. After rapid transfer into a closed chamber containing room air the amount of gas extracted from the sample by diffusion was measured by gas chromatography. Corrections for unextracted gas and for gas lost during the transfer of the sample were applied. The following mean values for the solubility coefficients, in mumol-1(-1)-torr(-1), were found: chloro-difluoro-methane (Freon 22), 56.0; acetylene, 55.5; nitrous oxide, 27.7; methane, 2.42; hydrogen, 1.13; helium, 0.608; sulfur hexafluoride, 0.559. The relationships between solubility in tissue, in water and in olive oil are discussed.", "contents": "Solubility of various inert gases in rat skeletal muscle. For the determination of solubility coefficients, isolated rat abdominal muscles were equilibrated at 37 degrees C with various inert gases saturated with water vapor. After rapid transfer into a closed chamber containing room air the amount of gas extracted from the sample by diffusion was measured by gas chromatography. Corrections for unextracted gas and for gas lost during the transfer of the sample were applied. The following mean values for the solubility coefficients, in mumol-1(-1)-torr(-1), were found: chloro-difluoro-methane (Freon 22), 56.0; acetylene, 55.5; nitrous oxide, 27.7; methane, 2.42; hydrogen, 1.13; helium, 0.608; sulfur hexafluoride, 0.559. The relationships between solubility in tissue, in water and in olive oil are discussed."} {"id": "PMID:171622", "title": "Diffusivity of various inert gases in rat skeletal muscle.", "content": "Krogh's diffusion constant (K) was determined for various inert gases in isolated rat abdominal muscle at 37 degrees C by measuring the amount of gas diffusing per unit time and partial pressure difference through a portion of the muscle of known surface area and thickness. The following mean values for K, in 10(-9) mmol-min-1-cm-1-torr-1, were obtained: C2H2, 42.2; N2O, 20.0; CHClF2, 18.8; H2, 1.67; He, 1.42; CH4, 1.27; SF6, 0.081. From Krogh's diffusion constant, the diffusion coefficient (D) was calculated using the solubility coefficient determined previously in the same preparation. The D values thus obtained were found to be about half the D values in water at 37 degrees C. Model calculations show that for gases with high lipid/water partition coefficient, D in tissues containing lipid is underestimated by this method. Graham's law (inverse proportionality between D and square root of molecular mass) was found to represent a useful approximation for these gases. A better correlation, however, was obtained between D and the molecular diameter.", "contents": "Diffusivity of various inert gases in rat skeletal muscle. Krogh's diffusion constant (K) was determined for various inert gases in isolated rat abdominal muscle at 37 degrees C by measuring the amount of gas diffusing per unit time and partial pressure difference through a portion of the muscle of known surface area and thickness. The following mean values for K, in 10(-9) mmol-min-1-cm-1-torr-1, were obtained: C2H2, 42.2; N2O, 20.0; CHClF2, 18.8; H2, 1.67; He, 1.42; CH4, 1.27; SF6, 0.081. From Krogh's diffusion constant, the diffusion coefficient (D) was calculated using the solubility coefficient determined previously in the same preparation. The D values thus obtained were found to be about half the D values in water at 37 degrees C. Model calculations show that for gases with high lipid/water partition coefficient, D in tissues containing lipid is underestimated by this method. Graham's law (inverse proportionality between D and square root of molecular mass) was found to represent a useful approximation for these gases. A better correlation, however, was obtained between D and the molecular diameter."} {"id": "PMID:171624", "title": "The role of extracellular Ca2+ and cyclic nucleotides in the mechanism of enzyme secretion from the cat pancreas.", "content": "The role of Ca2+ in protein secretion from the isolated perfused cat's pancreas, the effect of the dibutyryl analogues of cAMP and cGMP, and the interrelation of Ca2+ and the nucleotides were studied. The following results were obtained: 1. Pancreatic enzyme secretion can be elicited by CaCl2 injections into the pancreatic arteries and is linearily related to the peak Ca2+ concentration in the effluent perfusate. Different background Ca2+ concentrations in the perfusate (3 mM or 0.125 mM) do not disturb this relation, indicating that no adaptation occurs. The effect of Ca2+ injections is of the same magnitude as that evoked by the hormones pancreozymin or acetylcholine. 2. Injections of Ca2+ potentiate the effects of dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), dibutyryl guanosine 3',5'-cyclic monophosphate (dbcGMP) or theophylline. 3. Infusion of low doses of pancreozymin increases the Ca2+ effect. The findings indicate that extracellular Ca2+ is involved in the mechanism of enzyme secretion and that Ca2+ and cyclic nucleotides have a synergistic action on the target.", "contents": "The role of extracellular Ca2+ and cyclic nucleotides in the mechanism of enzyme secretion from the cat pancreas. The role of Ca2+ in protein secretion from the isolated perfused cat's pancreas, the effect of the dibutyryl analogues of cAMP and cGMP, and the interrelation of Ca2+ and the nucleotides were studied. The following results were obtained: 1. Pancreatic enzyme secretion can be elicited by CaCl2 injections into the pancreatic arteries and is linearily related to the peak Ca2+ concentration in the effluent perfusate. Different background Ca2+ concentrations in the perfusate (3 mM or 0.125 mM) do not disturb this relation, indicating that no adaptation occurs. The effect of Ca2+ injections is of the same magnitude as that evoked by the hormones pancreozymin or acetylcholine. 2. Injections of Ca2+ potentiate the effects of dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), dibutyryl guanosine 3',5'-cyclic monophosphate (dbcGMP) or theophylline. 3. Infusion of low doses of pancreozymin increases the Ca2+ effect. The findings indicate that extracellular Ca2+ is involved in the mechanism of enzyme secretion and that Ca2+ and cyclic nucleotides have a synergistic action on the target."} {"id": "PMID:171625", "title": "S-adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma cell line.", "content": "Partial purification of DNA methylase from Novikoff rat hepatoma cells is described. Contamination with other proteins persists although the enzyme preparation has a high specific activity and is purified 980-fold over homogenate activity. Evidence suggests, but does not prove, that there may be more than one species of DNA methylase in these cells. The enzyme has two broad pH optima at pH 7.0 and 7.5 and most readily methylates heterologous denatured DNAs although complex reaction kinetics indicate that native DNAs may eventually be methylated to an equal or greater level. The preparation of undermethylated DNA from Novikoff cells is also described. Undermethylated homologous DNA is an 85-fold greater acceptor of methyl groups than fully methylated Novikoff cell DNA. In contrast to other DNA substrates, the enzyme preparation methylates native undermethylated homologous DNA at a 3.5-fold greater than denatured undermethylated homologous DNA.", "contents": "S-adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma cell line. Partial purification of DNA methylase from Novikoff rat hepatoma cells is described. Contamination with other proteins persists although the enzyme preparation has a high specific activity and is purified 980-fold over homogenate activity. Evidence suggests, but does not prove, that there may be more than one species of DNA methylase in these cells. The enzyme has two broad pH optima at pH 7.0 and 7.5 and most readily methylates heterologous denatured DNAs although complex reaction kinetics indicate that native DNAs may eventually be methylated to an equal or greater level. The preparation of undermethylated DNA from Novikoff cells is also described. Undermethylated homologous DNA is an 85-fold greater acceptor of methyl groups than fully methylated Novikoff cell DNA. In contrast to other DNA substrates, the enzyme preparation methylates native undermethylated homologous DNA at a 3.5-fold greater than denatured undermethylated homologous DNA."} {"id": "PMID:171626", "title": "The synthesis of the internucleotide (phosphodiester) bond by a base-catalysed reaction.", "content": "Potassium tert-butoxide in hexamethyl phosphoramide and dimethyl formamide provides an excellent catalyst for the reaction of a 3'-hydroxyl or a 5'-hydroxyl group of a nucleoside with an appropriate nucleoside phosphorofluoridate to yield the dinucleoside phosphate. This paper describes the experiments leading to the development of this reaction together with the synthesis of thymidylyl-(5' leads to 3')-thymidine (dT-dT).", "contents": "The synthesis of the internucleotide (phosphodiester) bond by a base-catalysed reaction. Potassium tert-butoxide in hexamethyl phosphoramide and dimethyl formamide provides an excellent catalyst for the reaction of a 3'-hydroxyl or a 5'-hydroxyl group of a nucleoside with an appropriate nucleoside phosphorofluoridate to yield the dinucleoside phosphate. This paper describes the experiments leading to the development of this reaction together with the synthesis of thymidylyl-(5' leads to 3')-thymidine (dT-dT)."} {"id": "PMID:171627", "title": "Sequences spanning the EcoRI substrate site.", "content": "Substrate recognition by the EcoRI restriction endonuclease was investigated by analysis of the nucleotide sequences at the sites of enzymatic cleavage in various DNA molecules. 5'-end labeling and homochromatographic fingerprinting led to the determination of a 17-base-pair sequence spanning the EcoRI site of simian virus 40 DNA and a 15-base-pair sequence overlapping the EcoRI site of Col El plasmid DNA. Three other DNAs were similarly tested, although extended sequences were not determined in these cases. The EcoRI site was shown to be symmetric double-stranded equivalent of -N-G-A-A-T-T-C-N-.", "contents": "Sequences spanning the EcoRI substrate site. Substrate recognition by the EcoRI restriction endonuclease was investigated by analysis of the nucleotide sequences at the sites of enzymatic cleavage in various DNA molecules. 5'-end labeling and homochromatographic fingerprinting led to the determination of a 17-base-pair sequence spanning the EcoRI site of simian virus 40 DNA and a 15-base-pair sequence overlapping the EcoRI site of Col El plasmid DNA. Three other DNAs were similarly tested, although extended sequences were not determined in these cases. The EcoRI site was shown to be symmetric double-stranded equivalent of -N-G-A-A-T-T-C-N-."} {"id": "PMID:171628", "title": "Mapping the transcription site of the SV40-specific late 16 S mRNA.", "content": "This paper describes the purification of polysomal RNA from SV40-lytically infected CV1 (monkey) cells and separation of the two distinct classes of SV40-specific mRNA sedimenting at 16 S and 19 S. These classes have been hybridized with the whole SV40 DNA genome as well as with the SV40 Hind fragments. The results have permitted the mapping of SV40-specific late 16 S mRNA from approximately 0.945 to 0.175 map units.", "contents": "Mapping the transcription site of the SV40-specific late 16 S mRNA. This paper describes the purification of polysomal RNA from SV40-lytically infected CV1 (monkey) cells and separation of the two distinct classes of SV40-specific mRNA sedimenting at 16 S and 19 S. These classes have been hybridized with the whole SV40 DNA genome as well as with the SV40 Hind fragments. The results have permitted the mapping of SV40-specific late 16 S mRNA from approximately 0.945 to 0.175 map units."} {"id": "PMID:171639", "title": "Effect of various concentrations of protein in chick diet upon the metabolic enzymes of glycine and serine.", "content": "The effect of feeding low protein diets with and without 2% glycine or 2% L-serine to chicks upon the enzymes concerned in the matabolism of glycine and serine has been determined. D-3-phosphoglycerate dehydrogenase (EC 1.1.1.s), hosphoserine phosphatase (EC 3.1.3.3), and serine hydroxymethyltransferase (EC 2.1.2.1) activities were significantly increased in livers from chicks fed 75% protein diets as compared to liver enzyme activities from chicks fed either 24% chick starter, 2% or 25% protein diets. Phosphoserine phosphatase activity was significantly higher in kidney tissue of chicks fed 75% protein diets. Livers from chicks fed 25% protein diets had a higher activity for D-3-phosphoglycerate dehydrogenase and phosphoserine phosphatase than did those fed chick starter or 2% protein diets. D-3-phosphoglycerate dehydrogenase and phosphoserine phosphatase activities were higher in livers from chicks fed 2% protein, 2% protein + 2% glycine, and 2% protein + 2% L-serine diets when compared to those from chicks fed low protein diets with supplemental methionine or cysteine. Serine dehydratase (EC 4.2.1.13), glycerate dehydrogenase (EC 1.1.1.29) and hydroxypyruvate-P: L-glutamate transaminase activities remained constant in livers from chicks fed all experimental diets. The uric acid concentration was significantly increased in plasma from chicks fed the high protein diets which suggests that D-3-phosphoglycerate dehydrogenase, phosphoserine phosphatase and serine hydroxymethyltransferase activities were increased because of the high requirement for glycine in uric acid formation. The 75% protein diet provided three times as much glycine as the 25% protein diet which may have met the increased need for glycine for uric acid formation.", "contents": "Effect of various concentrations of protein in chick diet upon the metabolic enzymes of glycine and serine. The effect of feeding low protein diets with and without 2% glycine or 2% L-serine to chicks upon the enzymes concerned in the matabolism of glycine and serine has been determined. D-3-phosphoglycerate dehydrogenase (EC 1.1.1.s), hosphoserine phosphatase (EC 3.1.3.3), and serine hydroxymethyltransferase (EC 2.1.2.1) activities were significantly increased in livers from chicks fed 75% protein diets as compared to liver enzyme activities from chicks fed either 24% chick starter, 2% or 25% protein diets. Phosphoserine phosphatase activity was significantly higher in kidney tissue of chicks fed 75% protein diets. Livers from chicks fed 25% protein diets had a higher activity for D-3-phosphoglycerate dehydrogenase and phosphoserine phosphatase than did those fed chick starter or 2% protein diets. D-3-phosphoglycerate dehydrogenase and phosphoserine phosphatase activities were higher in livers from chicks fed 2% protein, 2% protein + 2% glycine, and 2% protein + 2% L-serine diets when compared to those from chicks fed low protein diets with supplemental methionine or cysteine. Serine dehydratase (EC 4.2.1.13), glycerate dehydrogenase (EC 1.1.1.29) and hydroxypyruvate-P: L-glutamate transaminase activities remained constant in livers from chicks fed all experimental diets. The uric acid concentration was significantly increased in plasma from chicks fed the high protein diets which suggests that D-3-phosphoglycerate dehydrogenase, phosphoserine phosphatase and serine hydroxymethyltransferase activities were increased because of the high requirement for glycine in uric acid formation. The 75% protein diet provided three times as much glycine as the 25% protein diet which may have met the increased need for glycine for uric acid formation."} {"id": "PMID:171640", "title": "Mercuric chloride effects on the activities of some hepatic enzymes in chicks.", "content": "Three groups of 6 male chicks each were fed a commercial diet and were given drinking water which contained either 0, 150 or 300 mug. of mercury/ml. as mercuric chloride from hatching to 3 weeks of age. The chicks were killed, the livers were removed and weighed, and the activities of selected enzymes were measured in the 800 X gav supernatant fractions of the liver homogenates. Liver weights were depressed from control values in chicks receiving 300 p.p.m. mercury but not in chicks receiving 150 p.p.m. Fatty acid synthetase specific activity was depressed by both levels of added mercury, but microsomal fatty acid elongation was depressed only by 300 p.p.m. of mercury. Both levels of added mercury stimulated acid phosphatase specific activity. The speecific activities of cytochrome c oxidase, glucose-6-phosphatase and 6-phosphogluconate dehydrogenase were unaffected by added mercury. The data support the hypothesis that mercury administration does not result in generalized hepatotoxicity.", "contents": "Mercuric chloride effects on the activities of some hepatic enzymes in chicks. Three groups of 6 male chicks each were fed a commercial diet and were given drinking water which contained either 0, 150 or 300 mug. of mercury/ml. as mercuric chloride from hatching to 3 weeks of age. The chicks were killed, the livers were removed and weighed, and the activities of selected enzymes were measured in the 800 X gav supernatant fractions of the liver homogenates. Liver weights were depressed from control values in chicks receiving 300 p.p.m. mercury but not in chicks receiving 150 p.p.m. Fatty acid synthetase specific activity was depressed by both levels of added mercury, but microsomal fatty acid elongation was depressed only by 300 p.p.m. of mercury. Both levels of added mercury stimulated acid phosphatase specific activity. The speecific activities of cytochrome c oxidase, glucose-6-phosphatase and 6-phosphogluconate dehydrogenase were unaffected by added mercury. The data support the hypothesis that mercury administration does not result in generalized hepatotoxicity."} {"id": "PMID:171635", "title": "Search for potential amoebicides. Part IV. Some hydrazones derivatives of 2-nitro-4-5-dimethoxybenzhydrazide and of 1-4-bis-[alpha(o-acetylhydrazino) phenethyl] piperazine.", "content": "By the condensation of 2-nitro-4-5-dimethoxybenzhydrazide and of 1,4-bis[alpha(O-acetylhydrazino) phenethyl] piperazine with various carbonyl compounds 42 hydrozones were synthesissed. Out of them 26 compounds were tested against the axenic-culture of E. histolytica at conc. of 125 mug/ml but no significant amoebicidal activity was observed.", "contents": "Search for potential amoebicides. Part IV. Some hydrazones derivatives of 2-nitro-4-5-dimethoxybenzhydrazide and of 1-4-bis-[alpha(o-acetylhydrazino) phenethyl] piperazine. By the condensation of 2-nitro-4-5-dimethoxybenzhydrazide and of 1,4-bis[alpha(O-acetylhydrazino) phenethyl] piperazine with various carbonyl compounds 42 hydrozones were synthesissed. Out of them 26 compounds were tested against the axenic-culture of E. histolytica at conc. of 125 mug/ml but no significant amoebicidal activity was observed."} {"id": "PMID:171642", "title": "Preparation of carcinoembryonic antigen (CEA) containing significantly increased amounts of galactose and galactosamine.", "content": "CEA was prepared by combined isoelectric precipitation, ultrafiltration and column chromatography under controlled conditions of pH. The resulting immunologically active materials were higher in carbohydrate (85-87%), N-acetyl galactosamine (10-11.5%) and galactose (28-32%) content than that previously reported. Differences in amino acid yield were also noted; the concentrations of aspartate, serine, glycine and alanine being higher and that of lysine, histidine, arginine, proline, valine, isoleucine, leucine and tyrosine were lower than that reported for CEA prepared by previous methods. The tumor tissues for CEA extraction were obtained from two Group O Rh positive deceased. Neither preparation showed Group A or B activity as measured by hemagglutination inhibition. It is suggested that the method of purification influences the carbohydrate and amino acid yields.", "contents": "Preparation of carcinoembryonic antigen (CEA) containing significantly increased amounts of galactose and galactosamine. CEA was prepared by combined isoelectric precipitation, ultrafiltration and column chromatography under controlled conditions of pH. The resulting immunologically active materials were higher in carbohydrate (85-87%), N-acetyl galactosamine (10-11.5%) and galactose (28-32%) content than that previously reported. Differences in amino acid yield were also noted; the concentrations of aspartate, serine, glycine and alanine being higher and that of lysine, histidine, arginine, proline, valine, isoleucine, leucine and tyrosine were lower than that reported for CEA prepared by previous methods. The tumor tissues for CEA extraction were obtained from two Group O Rh positive deceased. Neither preparation showed Group A or B activity as measured by hemagglutination inhibition. It is suggested that the method of purification influences the carbohydrate and amino acid yields."} {"id": "PMID:171646", "title": "Interaction of ubisemiquinone with a paramagnetic component in heart tissue.", "content": "The origin of most of the electron paramagnetic resonances obtained at low temperature and low microwave power from heart tissue and subcellular fractions derived therefrom is now understood. A signal that emerges on partial reduction with characteristic lines at 3227 G (0.3227 tesla) and 3309 G (0.3309 tesla) (at 9.2 GHz) and disappears again on full reduction has remained unidentified. According to its behavior on oxidation-reduction, the substance giving rise to this signal has the properties of a two-electron acceptor. The signal is strongly dependent on temperature and can only be well resolved at less than 20 degrees K. It is readily elicited in submitochondrial particles by partial reduction, but has not been observed in submitochondrial particles from which ubiquinone has been removed by pentane extraction. When ubiquinone is reincorporated into extracted submitochondrial particles, the signal is again easily produced by partial reduction. Electron paramagnetic resonance spectra of partially reduced submitochondrial particles recorded at 34 GHz show lines centered about g approximately 2 with the same separation (approximately 82 G; approximately 0.0082 tesla) as do 9.2 GHz spectra, whereas no lines are detected with a separation of approximately 82 X 34/9.2 G (0.0082 X 34/9.2 tesla). We suggest, on the basis of these observations, that the unidentified signal arises from an interaction of ubisemiquinone and a second paramagnetic species. Three obvious choices exist concerning this second species: ubisemiquinone, flavin semiquinone, or an iorn-sulfur center. It is not possible without much additional information to decide between these possibilities. Since we have never observed the signal in the absence of the membrane-bound, high-potential type iron-sulfur protein, we have considered involvement of this species in the interaction. However, according to computer simulations of the observed electron paramagnetic resonance spectra, which yield best fits for semiquinone-semiquinone interaction, the possibility that ubi- or flavin semiquinone is the interaction partner appears more likely at this time. The interaction appears to be of the magnetic dipole-dipole type, but it is not certain whether there is also a contribution from spin exchange coupling. If it is assumed that the signal is due to magnetic dipole-dipole interaction, the distance of the partners is less than or equal to 7.7 A.", "contents": "Interaction of ubisemiquinone with a paramagnetic component in heart tissue. The origin of most of the electron paramagnetic resonances obtained at low temperature and low microwave power from heart tissue and subcellular fractions derived therefrom is now understood. A signal that emerges on partial reduction with characteristic lines at 3227 G (0.3227 tesla) and 3309 G (0.3309 tesla) (at 9.2 GHz) and disappears again on full reduction has remained unidentified. According to its behavior on oxidation-reduction, the substance giving rise to this signal has the properties of a two-electron acceptor. The signal is strongly dependent on temperature and can only be well resolved at less than 20 degrees K. It is readily elicited in submitochondrial particles by partial reduction, but has not been observed in submitochondrial particles from which ubiquinone has been removed by pentane extraction. When ubiquinone is reincorporated into extracted submitochondrial particles, the signal is again easily produced by partial reduction. Electron paramagnetic resonance spectra of partially reduced submitochondrial particles recorded at 34 GHz show lines centered about g approximately 2 with the same separation (approximately 82 G; approximately 0.0082 tesla) as do 9.2 GHz spectra, whereas no lines are detected with a separation of approximately 82 X 34/9.2 G (0.0082 X 34/9.2 tesla). We suggest, on the basis of these observations, that the unidentified signal arises from an interaction of ubisemiquinone and a second paramagnetic species. Three obvious choices exist concerning this second species: ubisemiquinone, flavin semiquinone, or an iorn-sulfur center. It is not possible without much additional information to decide between these possibilities. Since we have never observed the signal in the absence of the membrane-bound, high-potential type iron-sulfur protein, we have considered involvement of this species in the interaction. However, according to computer simulations of the observed electron paramagnetic resonance spectra, which yield best fits for semiquinone-semiquinone interaction, the possibility that ubi- or flavin semiquinone is the interaction partner appears more likely at this time. The interaction appears to be of the magnetic dipole-dipole type, but it is not certain whether there is also a contribution from spin exchange coupling. If it is assumed that the signal is due to magnetic dipole-dipole interaction, the distance of the partners is less than or equal to 7.7 A."} {"id": "PMID:171643", "title": "[Determination of the relative volume of the incorporations of a lipid nature by Candida guilleirmondii yeast cultured on hydrocarbons].", "content": "The paper describes a method for measuring a relative volume of lipid incorporations into yeast Candida guilliermondii cultivated on hydrocarbons. A relative volume of the incorporations (mean ratio of the volume of lipid incorporations to the cell volume expressed as percentage) as compared with the hydrocarbon content in the cells expressed as percentage of the yeast dry weight is given for each yeast sample. A direct correlation between the hydrocarbon content and relative volume of lipid incorporations has been demonstrated. The distribution of lipid incorporations in yeast populations with a different content of hydrocarbons has been studied statistically.", "contents": "[Determination of the relative volume of the incorporations of a lipid nature by Candida guilleirmondii yeast cultured on hydrocarbons]. The paper describes a method for measuring a relative volume of lipid incorporations into yeast Candida guilliermondii cultivated on hydrocarbons. A relative volume of the incorporations (mean ratio of the volume of lipid incorporations to the cell volume expressed as percentage) as compared with the hydrocarbon content in the cells expressed as percentage of the yeast dry weight is given for each yeast sample. A direct correlation between the hydrocarbon content and relative volume of lipid incorporations has been demonstrated. The distribution of lipid incorporations in yeast populations with a different content of hydrocarbons has been studied statistically."} {"id": "PMID:171647", "title": "Location of histones on simian virus 40 DNA.", "content": "The physical location of histone molecules in a simian virus 40 DNA-histone complex isolated from purified virions was examined using site-specific restriction endonucleases. The complex contains four host histone species but lacks histone F1. Histones prevent complete cleavage of SV40 DNA by two restriction enzymes, HindIII and EcoRI. From the pattern of DNA fragments resulting from cleavage of the histone-DNA complex by the HindIII endonuclease, which makes six breaks on purified SV 40 DNA, we have concluded that histones are randomly arranged on SV40 DNA relative to restriction enzyme cleavage sites. The EcoRI endonuclease, which makes one break in SV40 NDA, was used to determine the degree of physical coverage of the SV 40 DNA molecule by histones. We observed that 80% of the EcoRI sites in the complex are accessible to the enzyme while 20% are \"closed.\" This degree of coverage is consistent with the mass ratio of DNA:histone in the complex as revealed by the buoyant density of the formaldehyde-fixed complex. We conclude that the histones in the complex are located randomly on the SV 40 genome and cover approximatley 20% of the DNA. These results suggest that the histone species F2b, F2al, F2a2, and F3 are bound without regard to nucleotide sequence of SV 40 DNA.", "contents": "Location of histones on simian virus 40 DNA. The physical location of histone molecules in a simian virus 40 DNA-histone complex isolated from purified virions was examined using site-specific restriction endonucleases. The complex contains four host histone species but lacks histone F1. Histones prevent complete cleavage of SV40 DNA by two restriction enzymes, HindIII and EcoRI. From the pattern of DNA fragments resulting from cleavage of the histone-DNA complex by the HindIII endonuclease, which makes six breaks on purified SV 40 DNA, we have concluded that histones are randomly arranged on SV40 DNA relative to restriction enzyme cleavage sites. The EcoRI endonuclease, which makes one break in SV40 NDA, was used to determine the degree of physical coverage of the SV 40 DNA molecule by histones. We observed that 80% of the EcoRI sites in the complex are accessible to the enzyme while 20% are \"closed.\" This degree of coverage is consistent with the mass ratio of DNA:histone in the complex as revealed by the buoyant density of the formaldehyde-fixed complex. We conclude that the histones in the complex are located randomly on the SV 40 genome and cover approximatley 20% of the DNA. These results suggest that the histone species F2b, F2al, F2a2, and F3 are bound without regard to nucleotide sequence of SV 40 DNA."} {"id": "PMID:171644", "title": "[Regulation of amylolytic complex enzyme biosynthesis in Endomycopsis fibuligera strain 20-9].", "content": "The effect of glucose and cyclic 3',5'-adenosine monophosphate (cAMP) on the synthesis of glucoamylase and alpha-amylase by the yeast Endomycopsis fibuligera str. 20-9 was investigated. The glucoamylase synthesis was inhibited by every concentration (0.05--3.0%) of glucose. The synthesis of alpha-amylase was significantly reduced by high concentrations (2.0-3.0%) of carbohydrate only. An addition of cAMP (1 X 10(-5) M) reversed compeltely the inhibitory effect of 0.5-2.0% glucose on the alpha-amylase synthesis and partially restored the glucoamylase synthesis. It is concluded that catabolite repression may be involved in the regulation of alpha-amylase and glucoamylase synthesis by Endomycopsis fibuligera str. 20-9 and that this type of regulation shows varying effectiveness in the enzyme synthesis.", "contents": "[Regulation of amylolytic complex enzyme biosynthesis in Endomycopsis fibuligera strain 20-9]. The effect of glucose and cyclic 3',5'-adenosine monophosphate (cAMP) on the synthesis of glucoamylase and alpha-amylase by the yeast Endomycopsis fibuligera str. 20-9 was investigated. The glucoamylase synthesis was inhibited by every concentration (0.05--3.0%) of glucose. The synthesis of alpha-amylase was significantly reduced by high concentrations (2.0-3.0%) of carbohydrate only. An addition of cAMP (1 X 10(-5) M) reversed compeltely the inhibitory effect of 0.5-2.0% glucose on the alpha-amylase synthesis and partially restored the glucoamylase synthesis. It is concluded that catabolite repression may be involved in the regulation of alpha-amylase and glucoamylase synthesis by Endomycopsis fibuligera str. 20-9 and that this type of regulation shows varying effectiveness in the enzyme synthesis."} {"id": "PMID:171645", "title": "[Effect of the method of cell disintegration on the aspartate kinase activity of preparations from Bacillus polymyxa var. Ross].", "content": "The influence of methods of cell disintegration of Bac. polymyxa on aspartate kinase activity (EC 2.7.2.4) was examined. The disruption by means of the Hews press yielded a more active preparation as compared with ultrasonic disintegration. The supernatant treatment with streptomycin sulphate increased the preparation activity 2-fold. Dialysis of the fraction with a high activity of aspartate kinase inactivated the enzyme by 80--85%. The relationship between the aspartate kinase activity and the portein and ATP concentration in the reaction mixture was established.", "contents": "[Effect of the method of cell disintegration on the aspartate kinase activity of preparations from Bacillus polymyxa var. Ross]. The influence of methods of cell disintegration of Bac. polymyxa on aspartate kinase activity (EC 2.7.2.4) was examined. The disruption by means of the Hews press yielded a more active preparation as compared with ultrasonic disintegration. The supernatant treatment with streptomycin sulphate increased the preparation activity 2-fold. Dialysis of the fraction with a high activity of aspartate kinase inactivated the enzyme by 80--85%. The relationship between the aspartate kinase activity and the portein and ATP concentration in the reaction mixture was established."} {"id": "PMID:171648", "title": "Hormonal effects on structure and catalytic properties of fructose 1,6-bisphosphatase.", "content": "Gluconeogenic conditions, such as administration of triamcinolone or alloxan diabetes, cause the following changes in the molecular structure and properties of rabbit liver fructose 1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11): (1) the appearance of traces (about 10%) of a lighter subunit; (2) loss of tryptophan from all of the subunits, including those that show no apparent change in molecular weight; (3) increase in requirement for the positive allosteric effector, histidine; (4) increase in amount of enzyme, but not its specific activity. These changes are identical to those induced by cold or fasting, and are related to increased activities of lysosomal proteases. The results suggest that lysosomes may act as mediators of gluconeogenic stimuli.", "contents": "Hormonal effects on structure and catalytic properties of fructose 1,6-bisphosphatase. Gluconeogenic conditions, such as administration of triamcinolone or alloxan diabetes, cause the following changes in the molecular structure and properties of rabbit liver fructose 1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11): (1) the appearance of traces (about 10%) of a lighter subunit; (2) loss of tryptophan from all of the subunits, including those that show no apparent change in molecular weight; (3) increase in requirement for the positive allosteric effector, histidine; (4) increase in amount of enzyme, but not its specific activity. These changes are identical to those induced by cold or fasting, and are related to increased activities of lysosomal proteases. The results suggest that lysosomes may act as mediators of gluconeogenic stimuli."} {"id": "PMID:171649", "title": "Inactivation of rabbit muscle phosphorylase phosphatase by cyclic AMP-dependent kinas.", "content": "Partially purified rabbit skeletal muscle phosphorylase phosphatase (EC 3.1.3.17; phosphoprotein phosphohydrolase) was inactivated when it was incubated with exogenous cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase), cyclic AMP, and ATP-Mg. Subsequent separation of the phosphatase by acrylamide gel electrophoresis or sucrose density centrifugation resulted in reactivation of the enzyme. The phosphatase decreased in molecular weight from approximately 70,000 to 52,000, and a phosphorylated inhibitor with molecular weight of 26,000 was found. Reactivation of phosphatase also occurred when it was incubated with MnCl2 or trypsin. The inhibitor was effective at less than 10(-8) M and was relatively heat stable. Its activity was destroyed by tryptic digestion and by dephosphorylation by a Mn-stimulated phosphatase. These observations support the possibility that phosphorylase phosphatase activity is controlled by cyclic AMP-dependent protein kinase and a Mn-stimulated phosphatase by a reaction involving phosphorylation and dephosphorylation of a protein phosphatase inhibitor.", "contents": "Inactivation of rabbit muscle phosphorylase phosphatase by cyclic AMP-dependent kinas. Partially purified rabbit skeletal muscle phosphorylase phosphatase (EC 3.1.3.17; phosphoprotein phosphohydrolase) was inactivated when it was incubated with exogenous cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase), cyclic AMP, and ATP-Mg. Subsequent separation of the phosphatase by acrylamide gel electrophoresis or sucrose density centrifugation resulted in reactivation of the enzyme. The phosphatase decreased in molecular weight from approximately 70,000 to 52,000, and a phosphorylated inhibitor with molecular weight of 26,000 was found. Reactivation of phosphatase also occurred when it was incubated with MnCl2 or trypsin. The inhibitor was effective at less than 10(-8) M and was relatively heat stable. Its activity was destroyed by tryptic digestion and by dephosphorylation by a Mn-stimulated phosphatase. These observations support the possibility that phosphorylase phosphatase activity is controlled by cyclic AMP-dependent protein kinase and a Mn-stimulated phosphatase by a reaction involving phosphorylation and dephosphorylation of a protein phosphatase inhibitor."} {"id": "PMID:171650", "title": "Interchain disulfide bonds in procollagen are located in a large nontriple-helical COOH-terminal domain.", "content": "Tadpole collagenase (EC 3.4.24.3) cleaved chick cranial bone procollagen into two triple-stranded fragments, PCA and PCB. Only PCB, with an estimated molecular weight of about 60,000 for each component chain after reduction, was found to contain interchain disulfide bonds. The analogous cleavage of collagen is known to produce a large NH2-terminal fragment with a molecular weight of 70,000 for each chain and a small COOH-terminal fragment containing chains of about 25,000 molecular weight. Since PCB was too small to represent the product NH2-terminal to the site of collagenase cleavage, localization of interchain disulfide bonds to a COOH-terminal domain in procollagen was indicated. This assignment was conformed by Dintzis-type short-term labeling experiments. Procollagen obtained by acid extraction of bone lacked the COOH-terminal disulfide-bonded domain. The findings support a model for procollagen consisting of three proalpha chains each containing nonhelical NH2-terminal extensions of 20,000 molecular weight and COOH-terminal extensions of about 35,000 molecular weight, the latter linked by interchani disulfide bonds.", "contents": "Interchain disulfide bonds in procollagen are located in a large nontriple-helical COOH-terminal domain. Tadpole collagenase (EC 3.4.24.3) cleaved chick cranial bone procollagen into two triple-stranded fragments, PCA and PCB. Only PCB, with an estimated molecular weight of about 60,000 for each component chain after reduction, was found to contain interchain disulfide bonds. The analogous cleavage of collagen is known to produce a large NH2-terminal fragment with a molecular weight of 70,000 for each chain and a small COOH-terminal fragment containing chains of about 25,000 molecular weight. Since PCB was too small to represent the product NH2-terminal to the site of collagenase cleavage, localization of interchain disulfide bonds to a COOH-terminal domain in procollagen was indicated. This assignment was conformed by Dintzis-type short-term labeling experiments. Procollagen obtained by acid extraction of bone lacked the COOH-terminal disulfide-bonded domain. The findings support a model for procollagen consisting of three proalpha chains each containing nonhelical NH2-terminal extensions of 20,000 molecular weight and COOH-terminal extensions of about 35,000 molecular weight, the latter linked by interchani disulfide bonds."} {"id": "PMID:171651", "title": "Effect of chemical inactivating agents on glucocorticoid receptor proteins in mouse and hamster cells.", "content": "The ffect of N-ethylmaleimide and iodoacetamide on the glucocorticoid receptor activity extracted from the cytosol of either mouse of hamster cells has been investigated. Treatment of mouse or hamster cytosol with N-ethylmaleimide or iodoacetamide rapidly inactivates the [3H]glucocorticoid hormone binding activity of either cytosol. Prebinding the glucocorticoid hormone, dexamethasone, to the cytosol receptor blocks the rapid inactivation of the receptor by N-ethylmaleimide. Treatment of the prebound hormone-receptor complex with iodoacetamide prevents the subsequent binding of the hormone-receptor complex to DNA without causing a dissociation of the complex. Although the conclusions may be limited by the lack of purity of the receptor, the results suggest that a sulfhydryl group is involved in the binding of glucocorticoid hormones to the receptor protein. In addition, the results suggest that iodoacetamide is inactivating a separate chemical site which is necessary for the binding of the hormone-receptor complex to DNA.", "contents": "Effect of chemical inactivating agents on glucocorticoid receptor proteins in mouse and hamster cells. The ffect of N-ethylmaleimide and iodoacetamide on the glucocorticoid receptor activity extracted from the cytosol of either mouse of hamster cells has been investigated. Treatment of mouse or hamster cytosol with N-ethylmaleimide or iodoacetamide rapidly inactivates the [3H]glucocorticoid hormone binding activity of either cytosol. Prebinding the glucocorticoid hormone, dexamethasone, to the cytosol receptor blocks the rapid inactivation of the receptor by N-ethylmaleimide. Treatment of the prebound hormone-receptor complex with iodoacetamide prevents the subsequent binding of the hormone-receptor complex to DNA without causing a dissociation of the complex. Although the conclusions may be limited by the lack of purity of the receptor, the results suggest that a sulfhydryl group is involved in the binding of glucocorticoid hormones to the receptor protein. In addition, the results suggest that iodoacetamide is inactivating a separate chemical site which is necessary for the binding of the hormone-receptor complex to DNA."} {"id": "PMID:171652", "title": "Cyclic AMP-mediated induction of ornithine decarboxylase of glioma and neuroblastoma cells.", "content": "The activity of ornithine decarboxylase (EC 4.1.1.17; L-ornithine carboxy-lyase) of C6-BU-1 glioma and N115 neuroblastoma cells increases significantly when confluent cultures are treated with compounds that increase cellular cAMP levels. These include norepinephrine or isoproterenol, and prostaglandin E1 or adenosine, which stimulate ornithine decarboxylase activity in C6-BU-1 glioma and N115 neuroblastoma cells, respectively. Ornithine decarboxylase activity is also elevated in confluent C6-BU-1 glioma cells treated with dibutyrylcAMP and theophylline, or after the glioma cells are fed with a serum-depleted medium in the presence of catecholamines and inhibitors of cyclic nucleotide phosphodiesterase. The activity of the enzyme increases 500- to 1000-fold, 2-6 hr after stationary-phase N115 neuroblastoma cells are fed with a serum-free medium, supplemented with phosphodiesterase inhibitors, adenosine, or prostaglandin E1. This stimulation is antagonized by carbamoyl choline and is blocked by actinomycin D or cycloheximide. These results suggest that the synthesis of ornithine decarboxylase of C6-BU-1 glioma and N115 neuroblastoma cells is controlled by cAMP.", "contents": "Cyclic AMP-mediated induction of ornithine decarboxylase of glioma and neuroblastoma cells. The activity of ornithine decarboxylase (EC 4.1.1.17; L-ornithine carboxy-lyase) of C6-BU-1 glioma and N115 neuroblastoma cells increases significantly when confluent cultures are treated with compounds that increase cellular cAMP levels. These include norepinephrine or isoproterenol, and prostaglandin E1 or adenosine, which stimulate ornithine decarboxylase activity in C6-BU-1 glioma and N115 neuroblastoma cells, respectively. Ornithine decarboxylase activity is also elevated in confluent C6-BU-1 glioma cells treated with dibutyrylcAMP and theophylline, or after the glioma cells are fed with a serum-depleted medium in the presence of catecholamines and inhibitors of cyclic nucleotide phosphodiesterase. The activity of the enzyme increases 500- to 1000-fold, 2-6 hr after stationary-phase N115 neuroblastoma cells are fed with a serum-free medium, supplemented with phosphodiesterase inhibitors, adenosine, or prostaglandin E1. This stimulation is antagonized by carbamoyl choline and is blocked by actinomycin D or cycloheximide. These results suggest that the synthesis of ornithine decarboxylase of C6-BU-1 glioma and N115 neuroblastoma cells is controlled by cAMP."} {"id": "PMID:171653", "title": "Human synoviocytes: activation and desensitization by prostaglandins and 1-epinephrine.", "content": "The human synoviocyte increases its intracellular adenosine 3':5'-cyclic monophosphate (cAMP) concentration significantly after incubation with prostaglandin E1, prostaglandin E2, or l-epinephrine. The cells can be desensitized to these same hormones. Hormone-induced desensitization is receptor site specific and associated with a significant increase in intracellular 3':5'-cyclic AMP phosphodiesterase (EC 3.1.4. 17; 3':5'-cyclic AMP 5'-nucleotidohydrolase) activity, whereas cAMP-induced desensitization is not hormone specific.", "contents": "Human synoviocytes: activation and desensitization by prostaglandins and 1-epinephrine. The human synoviocyte increases its intracellular adenosine 3':5'-cyclic monophosphate (cAMP) concentration significantly after incubation with prostaglandin E1, prostaglandin E2, or l-epinephrine. The cells can be desensitized to these same hormones. Hormone-induced desensitization is receptor site specific and associated with a significant increase in intracellular 3':5'-cyclic AMP phosphodiesterase (EC 3.1.4. 17; 3':5'-cyclic AMP 5'-nucleotidohydrolase) activity, whereas cAMP-induced desensitization is not hormone specific."} {"id": "PMID:171654", "title": "Surface ruffles as markers for studies of cell transformation by Rous sarcoma virus.", "content": "Confluent chick embryo fibroblasts infected with the Ts68 mutant of Rous sarcoma virus were examined by scanning electron microscopy at the permissive (36 degrees) and nonpermissive (41 degrees) temperatures for transformation. Infected cells shifted from 41 degrees to 36 degrees undergo a change in shape from elongated to rounded. This process is preceded by the appearance of surface ruffles on the cell. These surface ruffles are not observed on cells maintained at 41 degrees, appear as early as 0.5 hr after a shift to 36 degrees, and are common on cells maintained at 36 degrees. By 3.5 hr after the shift from 41 degrees to 36 degrees, cultures appear fully transformed by the criteria of cell roundedness and the presence of surface ruffles. This surface alteration of cells is the earliest event of those so far reported during the transformation process and is not dependent upon protein synthesis and extracellular plasminogen during the period of temperature shift.", "contents": "Surface ruffles as markers for studies of cell transformation by Rous sarcoma virus. Confluent chick embryo fibroblasts infected with the Ts68 mutant of Rous sarcoma virus were examined by scanning electron microscopy at the permissive (36 degrees) and nonpermissive (41 degrees) temperatures for transformation. Infected cells shifted from 41 degrees to 36 degrees undergo a change in shape from elongated to rounded. This process is preceded by the appearance of surface ruffles on the cell. These surface ruffles are not observed on cells maintained at 41 degrees, appear as early as 0.5 hr after a shift to 36 degrees, and are common on cells maintained at 36 degrees. By 3.5 hr after the shift from 41 degrees to 36 degrees, cultures appear fully transformed by the criteria of cell roundedness and the presence of surface ruffles. This surface alteration of cells is the earliest event of those so far reported during the transformation process and is not dependent upon protein synthesis and extracellular plasminogen during the period of temperature shift."} {"id": "PMID:171655", "title": "Chemotactic signals induce cell differentiation in Dictyostelium discoideum.", "content": "Experiments carried out with the aid of cellophane membranes demonstrate that the morphogenetic block of certain nonaggregating, \"aggregateless,\" mutants may be overcome by diffusible factors excreted by aggregating wild-type cells. The same differentiation process into aggregation-competent cell is observed if mutant amoebae are subjected to external 3':5'-cAMP pulses imposed at 5 min intervals. Wild-type amoebae also respond to cAMP pulses, since the onset of differentiation is more precocious in pulsed than in unpulsed populations. These data suggest that chemotactic signals act as an inducer of cell differentiation.", "contents": "Chemotactic signals induce cell differentiation in Dictyostelium discoideum. Experiments carried out with the aid of cellophane membranes demonstrate that the morphogenetic block of certain nonaggregating, \"aggregateless,\" mutants may be overcome by diffusible factors excreted by aggregating wild-type cells. The same differentiation process into aggregation-competent cell is observed if mutant amoebae are subjected to external 3':5'-cAMP pulses imposed at 5 min intervals. Wild-type amoebae also respond to cAMP pulses, since the onset of differentiation is more precocious in pulsed than in unpulsed populations. These data suggest that chemotactic signals act as an inducer of cell differentiation."} {"id": "PMID:171656", "title": "Target cells in bone for parathormone and calcitonin are different: enrichment for each cell type by sequential digestion of mouse calvaria and selective adhesion to polymeric surfaces.", "content": "Six populations of bone cells (populations 1-6) were obtained by sequential digestion of mouse calvaria with collagenase and trypsin. After release from the tissue, each cell population was cultured for seven days. Parathormone, but not calcitonin, elicited an increase in intracellular cyclic AMP in the cells of populations 4, 5, and 6. In contrast, both hormones elicited increases in cyclic AMP in populations 2 and 3 but had no effect on population 1. When the cells of population 2 were exposed to a Falcontissue culture polystyrene surface for periods of time up to 5 min, many cells adhered. The nonadhering cell population contained a lesser proportion of cells responsive to calcitonin, whereas the adhering population contained a greater proportion responsive to this hormone. Conversely, when the cells of population 2 were exposed to an acid-treated nylon surface, the nonadhering cells contained a larger proportion of those responsive to calcitonin and a smaller proportion responsive to parathormone. When those cells that were enriched for calcitonin responsiveness were examined, we found an increased proportion that exhibited an asymmetric bipolar morphology. These differed from large amorphous, often binucleate, cells which predominated in those populations that responded exclusively to parathormone. These results establish that bone contains at least two types of target cells--one that responds to parathormone but not calcitonin, the other that responds predominantly to calcitonin.", "contents": "Target cells in bone for parathormone and calcitonin are different: enrichment for each cell type by sequential digestion of mouse calvaria and selective adhesion to polymeric surfaces. Six populations of bone cells (populations 1-6) were obtained by sequential digestion of mouse calvaria with collagenase and trypsin. After release from the tissue, each cell population was cultured for seven days. Parathormone, but not calcitonin, elicited an increase in intracellular cyclic AMP in the cells of populations 4, 5, and 6. In contrast, both hormones elicited increases in cyclic AMP in populations 2 and 3 but had no effect on population 1. When the cells of population 2 were exposed to a Falcontissue culture polystyrene surface for periods of time up to 5 min, many cells adhered. The nonadhering cell population contained a lesser proportion of cells responsive to calcitonin, whereas the adhering population contained a greater proportion responsive to this hormone. Conversely, when the cells of population 2 were exposed to an acid-treated nylon surface, the nonadhering cells contained a larger proportion of those responsive to calcitonin and a smaller proportion responsive to parathormone. When those cells that were enriched for calcitonin responsiveness were examined, we found an increased proportion that exhibited an asymmetric bipolar morphology. These differed from large amorphous, often binucleate, cells which predominated in those populations that responded exclusively to parathormone. These results establish that bone contains at least two types of target cells--one that responds to parathormone but not calcitonin, the other that responds predominantly to calcitonin."} {"id": "PMID:171657", "title": "Enhanced representation of HL-A antigens on human lymphocytes after mitogenesis induced by phytohemagglutinin or Epstein-Barr virus.", "content": "The amount of HL-A antigens present on the peripheral blood lymphocytes of a single human donor was increased about 11-fold after stimulation with phytohemagglutinin and 36-fold after transformation with Epstein-Barr virus. This increase applied to all four HL-A specificities of these cells. The response to phytohemagglutinin was dependent on dose and was first observed at 12 hr of incubation. Measurements of the amount of surface membranes by geometry, by radioiodinatable surface proteins, and by 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) assay all indicated that the enhanced representation of HL-A antigens after stimulation by phytohemagglutinin or transformation by Epstein-Barr virus must be due to an increase in the density of these antigens on the cell surface.", "contents": "Enhanced representation of HL-A antigens on human lymphocytes after mitogenesis induced by phytohemagglutinin or Epstein-Barr virus. The amount of HL-A antigens present on the peripheral blood lymphocytes of a single human donor was increased about 11-fold after stimulation with phytohemagglutinin and 36-fold after transformation with Epstein-Barr virus. This increase applied to all four HL-A specificities of these cells. The response to phytohemagglutinin was dependent on dose and was first observed at 12 hr of incubation. Measurements of the amount of surface membranes by geometry, by radioiodinatable surface proteins, and by 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) assay all indicated that the enhanced representation of HL-A antigens after stimulation by phytohemagglutinin or transformation by Epstein-Barr virus must be due to an increase in the density of these antigens on the cell surface."} {"id": "PMID:171658", "title": "Thyroid hormone binding by a component of mitochondrial membrane.", "content": "The thyroid hormone, triiodothyronine, has been shown to be bound by the intranuclear chromatin protein associated with active DNA, where it is believed to stimulate transcription. Evidence exists that the thyroid hormones have direct action not only on nuclei, but also on mitochondria. Threfore, specific proteins that bind thyroid hormones in the mitochondria should be demonstrable. Mitochondria were isolated from homogenized rat livers by sedimentation through 0.25 M sucrose solution, followed by washing four times to free them of microsomes. Strong binding of thyroid hormones was observed in mitochondrial fractions prepared from both the membranes and the matrix. After incubation in an ice bath with increasing amonts of triiodothyronine with added tracer [125I]triiodothyronine, the matrix infrequently contained specific saturable receptor sites, but usually exhibited strong \"nonspecific\" interaction...", "contents": "Thyroid hormone binding by a component of mitochondrial membrane. The thyroid hormone, triiodothyronine, has been shown to be bound by the intranuclear chromatin protein associated with active DNA, where it is believed to stimulate transcription. Evidence exists that the thyroid hormones have direct action not only on nuclei, but also on mitochondria. Threfore, specific proteins that bind thyroid hormones in the mitochondria should be demonstrable. Mitochondria were isolated from homogenized rat livers by sedimentation through 0.25 M sucrose solution, followed by washing four times to free them of microsomes. Strong binding of thyroid hormones was observed in mitochondrial fractions prepared from both the membranes and the matrix. After incubation in an ice bath with increasing amonts of triiodothyronine with added tracer [125I]triiodothyronine, the matrix infrequently contained specific saturable receptor sites, but usually exhibited strong \"nonspecific\" interaction..."} {"id": "PMID:171659", "title": "C-type virus particles in placenta of normal healthy Sprague-Dawley rats.", "content": "C-type virus particles were found on electron-microscopic examination in placentas from two out of four young healthy Sprague-Dawley rats. One of these specimens contained virus particles budding from the plasma membranes of cells in the junctional zone of the placenta, i.e., the region where the fetal and maternal cell layers meet. In the other placenta, immature and mature C-type virus particles were found among cell debris also in the junctional region. This observation adds another species of animals to those recently reported, such as rhesus and baboon monkeys, as well as humans, in which C-type virus particles were found in the placenta. The presence of C-type viicant in view of the fact that a considerable number of these animals develop spontaneously a variety of malignant tumors, occasionally also leukemia and malignant lymphomas; however, none of these spontaneous tumors reveals the presence of virus particles on electron-microscopic examination. The nature of virus particles detected in rat placenta remains to be determined. As a working hypothesis, it is possible to assume that they may represent the passage of latent, presumably oncogenic, viruses transmitted \"vertically\" from parents to offspring. In the course of this passage some of them may be formed, emerging temporarily from their latency, before losing their identity and being again incorporated into the cell genetic components.", "contents": "C-type virus particles in placenta of normal healthy Sprague-Dawley rats. C-type virus particles were found on electron-microscopic examination in placentas from two out of four young healthy Sprague-Dawley rats. One of these specimens contained virus particles budding from the plasma membranes of cells in the junctional zone of the placenta, i.e., the region where the fetal and maternal cell layers meet. In the other placenta, immature and mature C-type virus particles were found among cell debris also in the junctional region. This observation adds another species of animals to those recently reported, such as rhesus and baboon monkeys, as well as humans, in which C-type virus particles were found in the placenta. The presence of C-type viicant in view of the fact that a considerable number of these animals develop spontaneously a variety of malignant tumors, occasionally also leukemia and malignant lymphomas; however, none of these spontaneous tumors reveals the presence of virus particles on electron-microscopic examination. The nature of virus particles detected in rat placenta remains to be determined. As a working hypothesis, it is possible to assume that they may represent the passage of latent, presumably oncogenic, viruses transmitted \"vertically\" from parents to offspring. In the course of this passage some of them may be formed, emerging temporarily from their latency, before losing their identity and being again incorporated into the cell genetic components."} {"id": "PMID:171660", "title": "Identification of the 5' end of Rous sarcoma virus RNA.", "content": "The 5'-terminal triphosphate of the 35S RNA isolated from Rous sarcoma virus is blocked by 7-methylguanosine in 5' linkage with the penultimate nucleoside which is methylated in the 2'-O-ribose position, a type of endgroup found in all animal mRNAs investigated during the past year. The specific nuclease-resistant terminal fragment of RSV RNA has the structure 7mG5'ppp5'GmpCp-. This finding supports the belief that RNA of Rous sarcoma virus represents a (+) strand messenger which may be directly translated upon infection.", "contents": "Identification of the 5' end of Rous sarcoma virus RNA. The 5'-terminal triphosphate of the 35S RNA isolated from Rous sarcoma virus is blocked by 7-methylguanosine in 5' linkage with the penultimate nucleoside which is methylated in the 2'-O-ribose position, a type of endgroup found in all animal mRNAs investigated during the past year. The specific nuclease-resistant terminal fragment of RSV RNA has the structure 7mG5'ppp5'GmpCp-. This finding supports the belief that RNA of Rous sarcoma virus represents a (+) strand messenger which may be directly translated upon infection."} {"id": "PMID:171661", "title": "Reversible effects of chaotropic agents on the proton permeability of Escherichia coli membrane vesicles.", "content": "Extraction of E. coli ML 308-225 membrane vesicles with chaotropic agents causes the vesicles to become specifically permeable to protons. As a result, the vesicles no longer generate a membrane potential, interior negative, and they do not catalyze respiration-dependent lactose or proline transport. Treatment of the extracted vesicles with various carbodiimides decreases the permeability of the vesicle membrane to protons, causing them to regain their ability to generate a membrane potential. By this means, active transport is completely reactivated. Exposure of the vesicles to carbodiimides prior to extraction with chaotropic agents makes transport activity impervious to the effects of the chaotropes.", "contents": "Reversible effects of chaotropic agents on the proton permeability of Escherichia coli membrane vesicles. Extraction of E. coli ML 308-225 membrane vesicles with chaotropic agents causes the vesicles to become specifically permeable to protons. As a result, the vesicles no longer generate a membrane potential, interior negative, and they do not catalyze respiration-dependent lactose or proline transport. Treatment of the extracted vesicles with various carbodiimides decreases the permeability of the vesicle membrane to protons, causing them to regain their ability to generate a membrane potential. By this means, active transport is completely reactivated. Exposure of the vesicles to carbodiimides prior to extraction with chaotropic agents makes transport activity impervious to the effects of the chaotropes."} {"id": "PMID:171662", "title": "Receptor-mediated shifts in cGMP and cAMP levels in neuroblastoma cells.", "content": "3':5'-cGMP levels of neuroblastoma N1E-115 cells increase as much as 200-fold upon activation of muscarinic acetylcholine receptors, resulting in intracellular cGMP concentrations greater than 600 pmol/mg of protein. The cells also have receptors for adenosine which mediate an increase in 3':5'-cAMP levels. Unexpectedly, prostaglandin E1 was found to increase the concentrations of both cGMP and cAMP. Carbamylcholine, adenosine, and PGE1 were added to cells separately and in pairs to determine the effect of one compound on cell responses to another. Reciprocal inhibition, unilateral inhibition, additive, and nonadditive responses were observed with respect to cGMP and cAMP levels when different pairs of receptors were activated simultaneously.", "contents": "Receptor-mediated shifts in cGMP and cAMP levels in neuroblastoma cells. 3':5'-cGMP levels of neuroblastoma N1E-115 cells increase as much as 200-fold upon activation of muscarinic acetylcholine receptors, resulting in intracellular cGMP concentrations greater than 600 pmol/mg of protein. The cells also have receptors for adenosine which mediate an increase in 3':5'-cAMP levels. Unexpectedly, prostaglandin E1 was found to increase the concentrations of both cGMP and cAMP. Carbamylcholine, adenosine, and PGE1 were added to cells separately and in pairs to determine the effect of one compound on cell responses to another. Reciprocal inhibition, unilateral inhibition, additive, and nonadditive responses were observed with respect to cGMP and cAMP levels when different pairs of receptors were activated simultaneously."} {"id": "PMID:171663", "title": "Comparison between growth characteristics of an Epstein--Barr virus (EBV)-genome-negative lymphoma line and its EBV-converted subline in vitro.", "content": "The GC-BJAB cell line, which carries the Epstein--Barr virus (EBV), was derived from an EBV-genome-negative lymphoma line (BJAB) by EBV infection in vitro [G. B. Clements, G. Klein, and S. Povey (1975) Int. J. Cancer, in press]. Both lines grow at a similar rate at 37 degrees but they differ at other temperatures. BJAB grows well at 34 degrees, 37 degrees, and 39 degrees. GC-BJAB grows at 37 degrees and 39 degrees, but grows poorly at 34 degrees. At 37 degrees, GC-BJAB cultures can be maintained at the viable state for a long time after having reached saturation density (approximately 10(6) cells per ml). In contrast, BJAB cultures die very soon after having attained similar maximum density. Since the identity of the two cell lines has been critically established [Clements et al.; E. Svedmyr and M. Jondal (1975) Proc. Nat. Acad. Sci USA 72, 1622--1626; G. Klein, to be published; J. Zeuthen, personal communication] the remarkable differences in their growth properties must be attributed to the EBV genome.", "contents": "Comparison between growth characteristics of an Epstein--Barr virus (EBV)-genome-negative lymphoma line and its EBV-converted subline in vitro. The GC-BJAB cell line, which carries the Epstein--Barr virus (EBV), was derived from an EBV-genome-negative lymphoma line (BJAB) by EBV infection in vitro [G. B. Clements, G. Klein, and S. Povey (1975) Int. J. Cancer, in press]. Both lines grow at a similar rate at 37 degrees but they differ at other temperatures. BJAB grows well at 34 degrees, 37 degrees, and 39 degrees. GC-BJAB grows at 37 degrees and 39 degrees, but grows poorly at 34 degrees. At 37 degrees, GC-BJAB cultures can be maintained at the viable state for a long time after having reached saturation density (approximately 10(6) cells per ml). In contrast, BJAB cultures die very soon after having attained similar maximum density. Since the identity of the two cell lines has been critically established [Clements et al.; E. Svedmyr and M. Jondal (1975) Proc. Nat. Acad. Sci USA 72, 1622--1626; G. Klein, to be published; J. Zeuthen, personal communication] the remarkable differences in their growth properties must be attributed to the EBV genome."} {"id": "PMID:171664", "title": "Ultrastructural localization of insulin receptors on adipocytes.", "content": "The method for preparing a stable, biologically active, covalently linked ferritin--insulin complex has been modified to provide a 25-fold increase in yield compared to the original procedure while reducing the molar fatio of ferritin to insulin to 1:1 from 40:1. Ultrastructural studies of isolated adipocytes revealed specific binding of ferritin--insulin to the cell surface in irregular clusters associated with the glycocalyx coating. The number of ferritin--insulin molecules observed was consistent with the number of sulin molecules observed was consistent with the number of receptors calculated from 125I-labeled insulin binding studies. The ferritin--insulin was not observed in the cytoplasm of the cell but was found on the convave side of surface connected vesicles. These surface connected vesicles were part of an alveolar-like system of plasma membrane invaginations which project in various directions in the cytoplasm and by thin sectioning can appear as pinocytotic-like microvesicles. The morphological observations on ferritin--insulin binding were supported by the finding that 125I-labeled insulin binding was almost exclusively localized to highly purified plasma membranes isolated by fractionation of adipocytes after incubation with 125I-labeled insulin. These data supported the theory that insulin did not need to enter a cell to cause biological effects and was consistent with the negative cooperativity concept of insulin binding to cell receptors.", "contents": "Ultrastructural localization of insulin receptors on adipocytes. The method for preparing a stable, biologically active, covalently linked ferritin--insulin complex has been modified to provide a 25-fold increase in yield compared to the original procedure while reducing the molar fatio of ferritin to insulin to 1:1 from 40:1. Ultrastructural studies of isolated adipocytes revealed specific binding of ferritin--insulin to the cell surface in irregular clusters associated with the glycocalyx coating. The number of ferritin--insulin molecules observed was consistent with the number of sulin molecules observed was consistent with the number of receptors calculated from 125I-labeled insulin binding studies. The ferritin--insulin was not observed in the cytoplasm of the cell but was found on the convave side of surface connected vesicles. These surface connected vesicles were part of an alveolar-like system of plasma membrane invaginations which project in various directions in the cytoplasm and by thin sectioning can appear as pinocytotic-like microvesicles. The morphological observations on ferritin--insulin binding were supported by the finding that 125I-labeled insulin binding was almost exclusively localized to highly purified plasma membranes isolated by fractionation of adipocytes after incubation with 125I-labeled insulin. These data supported the theory that insulin did not need to enter a cell to cause biological effects and was consistent with the negative cooperativity concept of insulin binding to cell receptors."} {"id": "PMID:171665", "title": "In vitro infection of lymphoid cells by thymotropic radiation leukemia virus grown in vitro.", "content": "Murine lymphoid cells were infected in vitro with purified leukemogenic radiation leukemia virus (RadLV) produced by virus-induced lymphoblast cell lines. Thymocytes were shown to be highly susceptible to infection by the virus, whereas murine or other fibroblasts were refractory to it. Murine bone marrow and spleen cells were shown to be much less sensitive to infection by this thymotropic RadLV. By comparison, a B-tropic RadLV isolate (RadLV), propagated on a mouse fibroblast cell line, was noninfectious for lymphoid cells but infected fibroblasts. A correlation was shown to exist between in vitro infection of thymocytes, as assayed by immunofluorescence, and in vivo leukemogenicity of the thymotropic RadLV. This constitutes a rapid in vitro test for in vivo leukemogenicity of a natural lymphatic leukemia virus.", "contents": "In vitro infection of lymphoid cells by thymotropic radiation leukemia virus grown in vitro. Murine lymphoid cells were infected in vitro with purified leukemogenic radiation leukemia virus (RadLV) produced by virus-induced lymphoblast cell lines. Thymocytes were shown to be highly susceptible to infection by the virus, whereas murine or other fibroblasts were refractory to it. Murine bone marrow and spleen cells were shown to be much less sensitive to infection by this thymotropic RadLV. By comparison, a B-tropic RadLV isolate (RadLV), propagated on a mouse fibroblast cell line, was noninfectious for lymphoid cells but infected fibroblasts. A correlation was shown to exist between in vitro infection of thymocytes, as assayed by immunofluorescence, and in vivo leukemogenicity of the thymotropic RadLV. This constitutes a rapid in vitro test for in vivo leukemogenicity of a natural lymphatic leukemia virus."} {"id": "PMID:171666", "title": "Central role for magnesium in coordinate control of metabolism and growth in animal cells.", "content": "The rate of DNA synthesis in cultures of chicken embryo fibroblasts is reduced by deprivation of serum, high population density, and other \"physiological\" effectors, through a reduction in the number of cells in the S-period of the cell cycle. The same effect can be produced by drastically reducing the concentration of Mg++ added to the medium. This effect is erratic, however, and better control of [Mg++] can be achieved with phosphorylated compounds which preferentially bind Mg++. Both ATP and ADP, at concentrations in the medium less than or equal to [Mg++], stimulate DNA synthesis in cultures, and at greater concentrations inhibit DNA synthesis by affe-ting the proportion of cells in the S-period. Sodium pyrophosphate, which strongly complexes Mg++, causes little stimulation of DNA synthesis at low concentrations, but causes a striking decrease at concentrations exceeding [Mg++] of the medium. The inhibition can be fully reversed by adding an excess of Mg++, and the kinetics of increase in DNA synthesis resemble those which follow the restoration of serum to serum-deprived cultures. Limitation of [Mg++] by pyrophosphate also reduces the rates of RNA and protein synthesis, 2-deoxy-D-glucose uptake, and lactic acid production to an extent comparable to the reduction caused by the removal of serum from the medium. A model for the coordinate control of metabolism, differentiated function, and growth through the activity of divalent cations is described. The compartmentalization of Mg++ within the cell serves as the key element in this coordinate control by regulating those metabolic pathways in which the rate-limiting steps are transphosphorylation reactions.", "contents": "Central role for magnesium in coordinate control of metabolism and growth in animal cells. The rate of DNA synthesis in cultures of chicken embryo fibroblasts is reduced by deprivation of serum, high population density, and other \"physiological\" effectors, through a reduction in the number of cells in the S-period of the cell cycle. The same effect can be produced by drastically reducing the concentration of Mg++ added to the medium. This effect is erratic, however, and better control of [Mg++] can be achieved with phosphorylated compounds which preferentially bind Mg++. Both ATP and ADP, at concentrations in the medium less than or equal to [Mg++], stimulate DNA synthesis in cultures, and at greater concentrations inhibit DNA synthesis by affe-ting the proportion of cells in the S-period. Sodium pyrophosphate, which strongly complexes Mg++, causes little stimulation of DNA synthesis at low concentrations, but causes a striking decrease at concentrations exceeding [Mg++] of the medium. The inhibition can be fully reversed by adding an excess of Mg++, and the kinetics of increase in DNA synthesis resemble those which follow the restoration of serum to serum-deprived cultures. Limitation of [Mg++] by pyrophosphate also reduces the rates of RNA and protein synthesis, 2-deoxy-D-glucose uptake, and lactic acid production to an extent comparable to the reduction caused by the removal of serum from the medium. A model for the coordinate control of metabolism, differentiated function, and growth through the activity of divalent cations is described. The compartmentalization of Mg++ within the cell serves as the key element in this coordinate control by regulating those metabolic pathways in which the rate-limiting steps are transphosphorylation reactions."} {"id": "PMID:171667", "title": "Molecular weights of adrenocorticotropic hormone in extracts of anterior and intermediate-posterior lobes of mouse pituitary.", "content": "The molecular weight of the adrenocorticotropic hormone (ACTH) activity in extracts of the separated anterior and intermediate-posterior lobes of the mouse pituitary was determined by gel filtration in guanidine-HCl. Following dilution or removal of the guanidine-HCl, ACTH activity was quantitated by both radioimmunoassay and bioassay. Extracts of the intermediate-posterior lobe contain approximately a tenth as much ACTH activity as extracts of the anterior lobe. In extracts of both the anterior and the intermediate-posterior lobes, about half of the immunological ACTH activity is similar in size to porcine ACTH (molecular weight 4000--5500). Two higher molecular weight forms of ACTH account for the remainder of the ACTH activity. About 40% of the immunological ACTH activity in anterior lobe extracts has a molecular weight of 6500--9000. Extracts of both the anterior lobe and the intermediate-posterior lobe contain ACTH activity with a molecular weight of 20,000--30,000. While this 20,000--30,000 molecular weight ACTH accounts for only 5% of the immunological ACTH activity in the anterior lobe extracts, it accounts for half of the immunological ACTH activity in extracts of the intermediate-posterior lobe. Extracts of an ACTH-secreting mouse pituitary tumor cell line (AtT-20/D-16v) contain the same three molecular weight forms of ACTH. Each of the three molecular weight forms of ACTH has a characteristic ratio of biological ACTH activity to immunological ACTH activity, independent of the source of the material (anterior lobe, intermediate-posterior lobe, or mouse pituitary tumor cell line).", "contents": "Molecular weights of adrenocorticotropic hormone in extracts of anterior and intermediate-posterior lobes of mouse pituitary. The molecular weight of the adrenocorticotropic hormone (ACTH) activity in extracts of the separated anterior and intermediate-posterior lobes of the mouse pituitary was determined by gel filtration in guanidine-HCl. Following dilution or removal of the guanidine-HCl, ACTH activity was quantitated by both radioimmunoassay and bioassay. Extracts of the intermediate-posterior lobe contain approximately a tenth as much ACTH activity as extracts of the anterior lobe. In extracts of both the anterior and the intermediate-posterior lobes, about half of the immunological ACTH activity is similar in size to porcine ACTH (molecular weight 4000--5500). Two higher molecular weight forms of ACTH account for the remainder of the ACTH activity. About 40% of the immunological ACTH activity in anterior lobe extracts has a molecular weight of 6500--9000. Extracts of both the anterior lobe and the intermediate-posterior lobe contain ACTH activity with a molecular weight of 20,000--30,000. While this 20,000--30,000 molecular weight ACTH accounts for only 5% of the immunological ACTH activity in the anterior lobe extracts, it accounts for half of the immunological ACTH activity in extracts of the intermediate-posterior lobe. Extracts of an ACTH-secreting mouse pituitary tumor cell line (AtT-20/D-16v) contain the same three molecular weight forms of ACTH. Each of the three molecular weight forms of ACTH has a characteristic ratio of biological ACTH activity to immunological ACTH activity, independent of the source of the material (anterior lobe, intermediate-posterior lobe, or mouse pituitary tumor cell line)."} {"id": "PMID:171668", "title": "Periodate and concanavalin A induce blast transformation of rat lymphocytes by an indirect mechanism.", "content": "When rat lymph node cells, rendered incapable of division by treatment with mitomycin C, were then reacted with sodium metaperiodate (NaIO4), they stimulated the transformation of untreated, syngeneic lymph node cells in vitro. Unequivocal evidence that untreated lymph node cells responded in this situation was obtained by means of sex chromosome karyotype analysis. In experiments in which the ratio of responder to stimulator cells was varied between the limits of pure responder and pure stimulator cells at a constant cell density, [3H]thymidine incorporation increased linearly to a maximum at a ratio of 1:1, and then decreased linearly. These results suggest a predominantly bicellular reaction in which one periodate-treated cell stimulates only one responder cell. In experiments in which stimulator cells were reacted with periodate, but not treated with mitomycin C, and then mixed at a 1:1 ratio with untreated, syngeneic lymph node cells, karyotype analysis showed that both periodate-treated and untreated lymph node cells responded in significant numbers. Lymph node cells were cultured at various cell densities under three different conditions: one group was made up entirely of cells treated with periodate; a second group consisted of a 1:1 mixture of cells treated with periodate and untreated cells; the third group contained normal cells cultured in the presence of soluble concanavalin A. Expressed as [3H]thymidine incorporated per 10(6) cells, a progressive increase was found at the lower cell densities for all three groups, and identical slopes (about 2.5) were obtained when the results were plotted on a full logarithmic scale. Mitomycin C-treated lymph node cells incubated with concanavalin A and then thoroughly washed were found to be capable of transforming untreated, syngeneic lymph node cells. Maximal [3H]thymidine incorporation also occurred at a ratio of 1:1. These results show that, similarly to periodate stimulation, mitogenic stimulation by concanavalin A probably operates through an indirect mechanism, analogous to a mixed lymphocyte reaction. It is possible that other mitogenic agents also operate indirectly.", "contents": "Periodate and concanavalin A induce blast transformation of rat lymphocytes by an indirect mechanism. When rat lymph node cells, rendered incapable of division by treatment with mitomycin C, were then reacted with sodium metaperiodate (NaIO4), they stimulated the transformation of untreated, syngeneic lymph node cells in vitro. Unequivocal evidence that untreated lymph node cells responded in this situation was obtained by means of sex chromosome karyotype analysis. In experiments in which the ratio of responder to stimulator cells was varied between the limits of pure responder and pure stimulator cells at a constant cell density, [3H]thymidine incorporation increased linearly to a maximum at a ratio of 1:1, and then decreased linearly. These results suggest a predominantly bicellular reaction in which one periodate-treated cell stimulates only one responder cell. In experiments in which stimulator cells were reacted with periodate, but not treated with mitomycin C, and then mixed at a 1:1 ratio with untreated, syngeneic lymph node cells, karyotype analysis showed that both periodate-treated and untreated lymph node cells responded in significant numbers. Lymph node cells were cultured at various cell densities under three different conditions: one group was made up entirely of cells treated with periodate; a second group consisted of a 1:1 mixture of cells treated with periodate and untreated cells; the third group contained normal cells cultured in the presence of soluble concanavalin A. Expressed as [3H]thymidine incorporated per 10(6) cells, a progressive increase was found at the lower cell densities for all three groups, and identical slopes (about 2.5) were obtained when the results were plotted on a full logarithmic scale. Mitomycin C-treated lymph node cells incubated with concanavalin A and then thoroughly washed were found to be capable of transforming untreated, syngeneic lymph node cells. Maximal [3H]thymidine incorporation also occurred at a ratio of 1:1. These results show that, similarly to periodate stimulation, mitogenic stimulation by concanavalin A probably operates through an indirect mechanism, analogous to a mixed lymphocyte reaction. It is possible that other mitogenic agents also operate indirectly."} {"id": "PMID:171669", "title": "Plasma membrane alteration associated with malignant transformation in culture.", "content": "The intramembrane organization of the plasma membranes of nonmalignant cells in culture has been compared by freeze-fracturing with that of virally-transformed malignant cells. No dramatic differences are present in the distribution of intramembrane particles in the plasma membranes of these cells when the cells are examined without fixation or with mild fixation (glutaraldehyde treatment) prior to freezing. However, a redistribution of intramembrane particles into aggregates occurs in the membranes of nontransformed cells after treatment with glycerol. The aggregation of particles is extensive in normal chick embryo fibroblasts, and less extensive in mouse 3T3 cells. The glycerol-induced particle redistribution is not inhibited at 4 degrees, but it is inhibited by pretreatment with 2.5% glutaraldehyde. A significant number of the cells remain viable after the glycerol treatment, and the process is reversible. Particle aggregation does not appear to be related to either growth rate or cell density. Transformed Rous sarcoma virus/chick embryo fibroblasts and simian virus 40/3T3 cells have few particle aggregates after glycerol treatment. The plasma membranes of chick embryo fibroblasts transformed with a mutant of Rous sarcoma virus (TS-68) that is temperature sensitive for transformation, have few particle aggregates when grown at the permissive temperature (37 degrees). Extremely prominent particle aggregates are present in the plasma membranes of cells grown at the nonpermissive temperature (41 degrees). These observations indicate that there is an alteration in the plasma membrane associated with viral transformation which is related to a glycerol-sensitive mechanism that controls the distribution of intramembrane particles.", "contents": "Plasma membrane alteration associated with malignant transformation in culture. The intramembrane organization of the plasma membranes of nonmalignant cells in culture has been compared by freeze-fracturing with that of virally-transformed malignant cells. No dramatic differences are present in the distribution of intramembrane particles in the plasma membranes of these cells when the cells are examined without fixation or with mild fixation (glutaraldehyde treatment) prior to freezing. However, a redistribution of intramembrane particles into aggregates occurs in the membranes of nontransformed cells after treatment with glycerol. The aggregation of particles is extensive in normal chick embryo fibroblasts, and less extensive in mouse 3T3 cells. The glycerol-induced particle redistribution is not inhibited at 4 degrees, but it is inhibited by pretreatment with 2.5% glutaraldehyde. A significant number of the cells remain viable after the glycerol treatment, and the process is reversible. Particle aggregation does not appear to be related to either growth rate or cell density. Transformed Rous sarcoma virus/chick embryo fibroblasts and simian virus 40/3T3 cells have few particle aggregates after glycerol treatment. The plasma membranes of chick embryo fibroblasts transformed with a mutant of Rous sarcoma virus (TS-68) that is temperature sensitive for transformation, have few particle aggregates when grown at the permissive temperature (37 degrees). Extremely prominent particle aggregates are present in the plasma membranes of cells grown at the nonpermissive temperature (41 degrees). These observations indicate that there is an alteration in the plasma membrane associated with viral transformation which is related to a glycerol-sensitive mechanism that controls the distribution of intramembrane particles."} {"id": "PMID:171670", "title": "Enhancement of immunity against murine syngeneic tumors by a fraction extracted from non-pathogenic mycobacteria.", "content": "The data reported here demonstrate that a preparation extracted from nonpathogenic mycobacteria such as Mycobacterium smegmatis and hereafter referred to as interphase material protected mice against Ehrlich ascitic carcinoma, L-1210 leukemia, and another syngeneic lymphoid leukemia. Furthermore, mice treated by this preparation were much less susceptible to endotoxins than when stimulated by BCG (bacillus Calmette-Guerin) or M. smegmatis cells. Moreover, guinea pigs treated by interphase material administered in Freund's incomplete adjuvant showed an increased immune response, yet their sensitivity to tuberculin was much weaker than that of controls sensitized with Freund's complete adjuvant. Finally, resistance to Columbia SK virus infection could be demonstrated when interphase material was administered to mice prior to virus challenge.", "contents": "Enhancement of immunity against murine syngeneic tumors by a fraction extracted from non-pathogenic mycobacteria. The data reported here demonstrate that a preparation extracted from nonpathogenic mycobacteria such as Mycobacterium smegmatis and hereafter referred to as interphase material protected mice against Ehrlich ascitic carcinoma, L-1210 leukemia, and another syngeneic lymphoid leukemia. Furthermore, mice treated by this preparation were much less susceptible to endotoxins than when stimulated by BCG (bacillus Calmette-Guerin) or M. smegmatis cells. Moreover, guinea pigs treated by interphase material administered in Freund's incomplete adjuvant showed an increased immune response, yet their sensitivity to tuberculin was much weaker than that of controls sensitized with Freund's complete adjuvant. Finally, resistance to Columbia SK virus infection could be demonstrated when interphase material was administered to mice prior to virus challenge."} {"id": "PMID:171671", "title": "Tumor regression at an untreated site during immunotherapy of an identical distant tumor.", "content": "The effects of two immunotherapy regimens on the development of an untreated, uniformly lethal transplantable line-10 hepatoma in strain 2 guinea pigs were monitored during treatment of an identical tumor 10 cm away. Line-10 cells were injected intradermally simultaneously at each of two sites. When one site was treated 6 and 16 days later with rabbit antibody against guinea pig fibrin fragment E, the complete regression of the treated tumor, a 25--30% depression in the development of the untreated tumor, and an increased survival time were observed. In another group of animals, when one site was treated 5 days after tumor challenge with syngeneic or xenogeneic \"tumor-immune\" RNA in a regimen including syngeneic nonsensitive lymphoid cells and tumor-specific antigen, all animals survived after complete and apparently specific regression of the tumors at both the treated and untreated sites. For the RNA regimen, we have shown that immunotherapy of an intradermally established line-10 tumor results in complete abrogation of both the treated and a distant untreated tumor; i.e., demonstrating a systemic effect.", "contents": "Tumor regression at an untreated site during immunotherapy of an identical distant tumor. The effects of two immunotherapy regimens on the development of an untreated, uniformly lethal transplantable line-10 hepatoma in strain 2 guinea pigs were monitored during treatment of an identical tumor 10 cm away. Line-10 cells were injected intradermally simultaneously at each of two sites. When one site was treated 6 and 16 days later with rabbit antibody against guinea pig fibrin fragment E, the complete regression of the treated tumor, a 25--30% depression in the development of the untreated tumor, and an increased survival time were observed. In another group of animals, when one site was treated 5 days after tumor challenge with syngeneic or xenogeneic \"tumor-immune\" RNA in a regimen including syngeneic nonsensitive lymphoid cells and tumor-specific antigen, all animals survived after complete and apparently specific regression of the tumors at both the treated and untreated sites. For the RNA regimen, we have shown that immunotherapy of an intradermally established line-10 tumor results in complete abrogation of both the treated and a distant untreated tumor; i.e., demonstrating a systemic effect."} {"id": "PMID:171672", "title": "Relationship between A-type and C-type particles in cells infected by Rous sarcoma virus.", "content": "Chicken cells infected with avian RNA tumor virus often contain small cytoplasmic A-type particles which commonly exist as clusters of 50--100 particles when viewed in thin sections. These particles were found more consistently in Rous sarcoma virus-infected than Rous-associated virus-infected cultures, but were generally present in only a small fraction of the total infected cells. The results of the survey of cells infected with various strains of leukosis-sarcoma viruses led to the hypothesis that the A particles develop in cells undergoing cytopathological degeneration. The hypothesis explains also the evanescent nature of the appearance of these particles in infected cells. The application of immunoelectron microscopic methods using monospecific antisera against viral internal proteins revealed that the A particles contain components immunologically related to the proteins of C-type virus.", "contents": "Relationship between A-type and C-type particles in cells infected by Rous sarcoma virus. Chicken cells infected with avian RNA tumor virus often contain small cytoplasmic A-type particles which commonly exist as clusters of 50--100 particles when viewed in thin sections. These particles were found more consistently in Rous sarcoma virus-infected than Rous-associated virus-infected cultures, but were generally present in only a small fraction of the total infected cells. The results of the survey of cells infected with various strains of leukosis-sarcoma viruses led to the hypothesis that the A particles develop in cells undergoing cytopathological degeneration. The hypothesis explains also the evanescent nature of the appearance of these particles in infected cells. The application of immunoelectron microscopic methods using monospecific antisera against viral internal proteins revealed that the A particles contain components immunologically related to the proteins of C-type virus."} {"id": "PMID:171673", "title": "Analysis of oncornavirus RNA subunits by electron microscopy.", "content": "Subunits of oncornavirus (avian myeloblastosis virus) RNA were isolated from purified 60--70S viral RNA by heat dissociation. Molecules sedimenting at 35 S, assumed to be the major component of the viral genome, were visualized in the electron microscope and their lengths were statistically analyzed. The results indicate a rather heterogeneous population of molecules with five distinct, reproducible size groups, an observation that excludes the assumption of random degradation of the genome. In addition, molecules of 28 and 18S RNA, always present in oncornavirus RNA preparations, were examined with the same methods. Some of these molecules possess secondary-structure regions similar to those characteristic for ribosomal RNA.", "contents": "Analysis of oncornavirus RNA subunits by electron microscopy. Subunits of oncornavirus (avian myeloblastosis virus) RNA were isolated from purified 60--70S viral RNA by heat dissociation. Molecules sedimenting at 35 S, assumed to be the major component of the viral genome, were visualized in the electron microscope and their lengths were statistically analyzed. The results indicate a rather heterogeneous population of molecules with five distinct, reproducible size groups, an observation that excludes the assumption of random degradation of the genome. In addition, molecules of 28 and 18S RNA, always present in oncornavirus RNA preparations, were examined with the same methods. Some of these molecules possess secondary-structure regions similar to those characteristic for ribosomal RNA."} {"id": "PMID:171678", "title": "Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro.", "content": "Pancreatic islet cell vacuolization, hyperglycemia, and glucose intolerance develop in rats after oral administration of cyproheptadine (CPH). In order to determine whether these effects were associated with abnormal insulin secretion, pancreas segments from CPH-treated and control rats were compared for their ability to secrete insulin in response to several stimuli. Oral administration of CPH (45 mg/kg/day) to rats for 1 or 8 days inhibited glucose-mediated insulin secretion from pancreas segments obtained 3 and 24 hr after the last dose of the drug. Insulin secretion had returned to normal by 48 hr after drug administration. Intraperitoneal administration of the drug was less effective than oral administration in inhibiting in vitro insulin secretion. Other stimuli for insulin secretion (tolbutamide, glucagon, L-leucine, and dibutyryl 3',5'cyclic AMP), like glucose, were incapable of releasing normal amounts of insulin from pancreas segments of CPH-treated rats. CPH and a metabolite, desmethyl-CPH, inhibited glucose-stimulated insulin secretion when added in vitro to pancreas segments from control rats. This suggests that the inhibition of insulin secretion in pancreas segments taken from animals treated with CPH could be due, at least in part, to the presence of drug and its metabolite in the tissue. A previously observed reduction in the pancreatic content of insulin in CPH-treated rats may also contribute to the abnormal insulin release in animals given the drug.", "contents": "Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro. Pancreatic islet cell vacuolization, hyperglycemia, and glucose intolerance develop in rats after oral administration of cyproheptadine (CPH). In order to determine whether these effects were associated with abnormal insulin secretion, pancreas segments from CPH-treated and control rats were compared for their ability to secrete insulin in response to several stimuli. Oral administration of CPH (45 mg/kg/day) to rats for 1 or 8 days inhibited glucose-mediated insulin secretion from pancreas segments obtained 3 and 24 hr after the last dose of the drug. Insulin secretion had returned to normal by 48 hr after drug administration. Intraperitoneal administration of the drug was less effective than oral administration in inhibiting in vitro insulin secretion. Other stimuli for insulin secretion (tolbutamide, glucagon, L-leucine, and dibutyryl 3',5'cyclic AMP), like glucose, were incapable of releasing normal amounts of insulin from pancreas segments of CPH-treated rats. CPH and a metabolite, desmethyl-CPH, inhibited glucose-stimulated insulin secretion when added in vitro to pancreas segments from control rats. This suggests that the inhibition of insulin secretion in pancreas segments taken from animals treated with CPH could be due, at least in part, to the presence of drug and its metabolite in the tissue. A previously observed reduction in the pancreatic content of insulin in CPH-treated rats may also contribute to the abnormal insulin release in animals given the drug."} {"id": "PMID:171679", "title": "Scanning electron microscopy of glucocrticoid-treated hepatocytes and hepatoma cells in culture.", "content": "The morphological effects of exposure to hydrocortisone have been examined in two cell lines of liver origin by scanning electon microscopy. In one of these, an aneuploid line derived from a Morris hepatoma, the presence of hormone results not only in a suppression of cell proliferation, but in a marked flattening of the cells and loss of surface microvilli; in the other cell line, a diploid line derived from adult rat liver, the suppression of cell division is less marked, and the morphological effects of the hormone are far less striking. While the suppression of cell division in both of these cell lines is known to be rapidly reversible upon the removal of hormone, the presence of hormone causes the hepatoma cells to assume both monolayer growth characteristics and a morphology resembling those of cells derived from normal liver.", "contents": "Scanning electron microscopy of glucocrticoid-treated hepatocytes and hepatoma cells in culture. The morphological effects of exposure to hydrocortisone have been examined in two cell lines of liver origin by scanning electon microscopy. In one of these, an aneuploid line derived from a Morris hepatoma, the presence of hormone results not only in a suppression of cell proliferation, but in a marked flattening of the cells and loss of surface microvilli; in the other cell line, a diploid line derived from adult rat liver, the suppression of cell division is less marked, and the morphological effects of the hormone are far less striking. While the suppression of cell division in both of these cell lines is known to be rapidly reversible upon the removal of hormone, the presence of hormone causes the hepatoma cells to assume both monolayer growth characteristics and a morphology resembling those of cells derived from normal liver."} {"id": "PMID:171680", "title": "Analysis of the renin-angiotensin system during fasting in adult male rabbits.", "content": "Caloric deprivation for 3 days in adult male rabbits induced significant increases in daily urinary Na+ excretion, urinary volume and fluid intake as previously reported. These changes were accompanied by: (a) a significant reduction in plasma renin concentration; (b) an unchanged plasma renin activity; (c) a marked increase in the plasma angiotensinogen concentration; (d) a significant reduction in plasma angiotensin I; and (e) a significant increase in plasma angiotensin II. In a separate group of adult male rabbits, 3 days of caloric deprivation significantly increased the amount of converting enzyme in pulmonary parenchymal tissue. These findings correlate with the previously reported enhancement of mineralocortical hormone secretion and limiting effect of the latter on the natriuresis of caloric withdrawal. Since the increased mineralocortical hormone secretion does not prevent the natriuresis, the possibility that these striking changes in the components of the renin-angiotensin system during caloric deprivation may exert intrarenal effects is discussed.", "contents": "Analysis of the renin-angiotensin system during fasting in adult male rabbits. Caloric deprivation for 3 days in adult male rabbits induced significant increases in daily urinary Na+ excretion, urinary volume and fluid intake as previously reported. These changes were accompanied by: (a) a significant reduction in plasma renin concentration; (b) an unchanged plasma renin activity; (c) a marked increase in the plasma angiotensinogen concentration; (d) a significant reduction in plasma angiotensin I; and (e) a significant increase in plasma angiotensin II. In a separate group of adult male rabbits, 3 days of caloric deprivation significantly increased the amount of converting enzyme in pulmonary parenchymal tissue. These findings correlate with the previously reported enhancement of mineralocortical hormone secretion and limiting effect of the latter on the natriuresis of caloric withdrawal. Since the increased mineralocortical hormone secretion does not prevent the natriuresis, the possibility that these striking changes in the components of the renin-angiotensin system during caloric deprivation may exert intrarenal effects is discussed."} {"id": "PMID:171681", "title": "Fluorescent virus precipitin test.", "content": "A fluorescent virus precipitin test (FVPT) for the serologic identification of small particulate antigens such as viruses has been described. The test has several advantageous characteristics: (a) It is probably as sensitive as any serologic test (i.e., aggregates with dimensions of 0.2 mum are detectable; therefore, complexes containing as few as three large viruses would give a positive test). (b) Cultivation of the virus is not required. (c) Since an indirect test can be used, only a single fluorescent conjugate is needed to permit the detection of a number of viruses. (d) The indirect test can be used to detect antiviral antibody. (e) The FVPT is rapid and reliable. (f) Its simplicity should enhance its general acceptance and application.", "contents": "Fluorescent virus precipitin test. A fluorescent virus precipitin test (FVPT) for the serologic identification of small particulate antigens such as viruses has been described. The test has several advantageous characteristics: (a) It is probably as sensitive as any serologic test (i.e., aggregates with dimensions of 0.2 mum are detectable; therefore, complexes containing as few as three large viruses would give a positive test). (b) Cultivation of the virus is not required. (c) Since an indirect test can be used, only a single fluorescent conjugate is needed to permit the detection of a number of viruses. (d) The indirect test can be used to detect antiviral antibody. (e) The FVPT is rapid and reliable. (f) Its simplicity should enhance its general acceptance and application."} {"id": "PMID:171682", "title": "Adenosine, AMP, cyclic AMP, theophylline and the action and production of erythropoietin.", "content": "Erythropoiesis, as measured by the uptake of 59Fe into plethoric mice, is stimulated by adenosine, AMP, cyclic AMP, and dibutyryl cyclic AMP, but not by cytidine, its nucleotides or cyclic GMP. This stimulation is erythropoietin dependent, because it is prevented by anti-erythropoietin. Theophylline neither stimulates erythropoiesis nor potentiates the action of erythropoietin on bone marrow cells in plethoric mice. Theophylline does potentiate the production of erythropoietin in rats following a frief hypoxic exposure but does not cause a similar increase in mice.", "contents": "Adenosine, AMP, cyclic AMP, theophylline and the action and production of erythropoietin. Erythropoiesis, as measured by the uptake of 59Fe into plethoric mice, is stimulated by adenosine, AMP, cyclic AMP, and dibutyryl cyclic AMP, but not by cytidine, its nucleotides or cyclic GMP. This stimulation is erythropoietin dependent, because it is prevented by anti-erythropoietin. Theophylline neither stimulates erythropoiesis nor potentiates the action of erythropoietin on bone marrow cells in plethoric mice. Theophylline does potentiate the production of erythropoietin in rats following a frief hypoxic exposure but does not cause a similar increase in mice."} {"id": "PMID:171683", "title": "Absence of idoxuridine and persistence of herpes simplex virus in brains of patients being treated for encephalitis.", "content": "Thirty-two specimens of brain from five patients with encephalitis suspected to be caused by herpes simplex virus, type 1 (HSV-1) were assayed for antiviral activity. Each patient received 60-80 mg/kg/day of idoxuridine (IDU) by intravenous infusion. The antiviral assay does not measure anti-HSV-1 antibodies. Biopsies of brain in every patient taken before IDU was used, and portions of several regions of the brain at autopsy were available during courses of treatment in four of the five patients. The last patient died 7 days after completing treatment. A significant concentration of IDU (833 mug/ml) was measured transiently in the cerebrospinal fluid of one patient. Meninges and brains showed inflammatory changes. Within the sensitivity of the test (larger than or equal to 6 mug/g) all specimens contained no IDU. As given, IDU does not achieve therapeutic concentrations in human brain. Further clinical use of IDU in therapy of herpes simplex virus encephalitis is not indicated.", "contents": "Absence of idoxuridine and persistence of herpes simplex virus in brains of patients being treated for encephalitis. Thirty-two specimens of brain from five patients with encephalitis suspected to be caused by herpes simplex virus, type 1 (HSV-1) were assayed for antiviral activity. Each patient received 60-80 mg/kg/day of idoxuridine (IDU) by intravenous infusion. The antiviral assay does not measure anti-HSV-1 antibodies. Biopsies of brain in every patient taken before IDU was used, and portions of several regions of the brain at autopsy were available during courses of treatment in four of the five patients. The last patient died 7 days after completing treatment. A significant concentration of IDU (833 mug/ml) was measured transiently in the cerebrospinal fluid of one patient. Meninges and brains showed inflammatory changes. Within the sensitivity of the test (larger than or equal to 6 mug/g) all specimens contained no IDU. As given, IDU does not achieve therapeutic concentrations in human brain. Further clinical use of IDU in therapy of herpes simplex virus encephalitis is not indicated."} {"id": "PMID:171684", "title": "Evidence against phosphorylation of a cyclic AMP-dependent protein kinase from bovine tracheobronchial smooth muscle.", "content": "The data presented in this report are evidence against the autophosphorylation of the cyclic AMP-dependent protein kinase isolated from bovine tracheobronchial smooth muscle. This suggests that there may be a fundamental difference in the regulation in vivo of the protein kinases from bovine heart and tracheobronchial smooth muscle.", "contents": "Evidence against phosphorylation of a cyclic AMP-dependent protein kinase from bovine tracheobronchial smooth muscle. The data presented in this report are evidence against the autophosphorylation of the cyclic AMP-dependent protein kinase isolated from bovine tracheobronchial smooth muscle. This suggests that there may be a fundamental difference in the regulation in vivo of the protein kinases from bovine heart and tracheobronchial smooth muscle."} {"id": "PMID:171686", "title": "In vivo electron spin resonance in rats.", "content": "In vivo ESR studies have been made on Wistar and Sprague-Dawley rats using travelling wave helices implanted in the left lobe of the liver. Tissue regenerates completely around the Teflon-enclosed turns of the coil and histological studies have shown that it is composed of liver cells and connective tissue. Electron spin resonance studies of this tissue in vitro reported by Commoner and Ternberg in 1961 have demonstrated that it exhibits the 'tissue radical' signal. The implanted coils have detected, in vivo, a three-line spectrum due to a strong concentration of 4-hydroxy- 2,2,6,6-tetramethylpiperidine-1-oxyl free radical ('tempol'), a nitroxide spin label, injected either intramuscularly, intraperitoneally or intravenously into the experimental animal immediately prior to the measurement. They have also detected, in vivo, a similar three-line spectrum due to 'spin-labelled chlorpromazine', a tranquillizing drug to which this nitroxide spin label has been attached, injected intramuscularly or intraperitoneally into the animal immediately prior o the measurement. Work is currently in progress to increase the in vivo sensitivity of the implanted helices by menas of improved coupling techniques and the use of a time-averaging computer.", "contents": "In vivo electron spin resonance in rats. In vivo ESR studies have been made on Wistar and Sprague-Dawley rats using travelling wave helices implanted in the left lobe of the liver. Tissue regenerates completely around the Teflon-enclosed turns of the coil and histological studies have shown that it is composed of liver cells and connective tissue. Electron spin resonance studies of this tissue in vitro reported by Commoner and Ternberg in 1961 have demonstrated that it exhibits the 'tissue radical' signal. The implanted coils have detected, in vivo, a three-line spectrum due to a strong concentration of 4-hydroxy- 2,2,6,6-tetramethylpiperidine-1-oxyl free radical ('tempol'), a nitroxide spin label, injected either intramuscularly, intraperitoneally or intravenously into the experimental animal immediately prior to the measurement. They have also detected, in vivo, a similar three-line spectrum due to 'spin-labelled chlorpromazine', a tranquillizing drug to which this nitroxide spin label has been attached, injected intramuscularly or intraperitoneally into the animal immediately prior o the measurement. Work is currently in progress to increase the in vivo sensitivity of the implanted helices by menas of improved coupling techniques and the use of a time-averaging computer."} {"id": "PMID:171688", "title": "Correlation between in vivo and in vitro metabolic measurements. Maximum capacity for urea synthesis.", "content": "Estimations of enzyme activity in vivo have been or can often only be done at unphysiological conditions. A main biochemical goal is to correlate in vivo and in vitro measurements. A possible approach to this problem is presented based on forcing metabolic activity in vivo to the maximum for a certain metabolic sequence. Since the urea synthesis system, including maximal rates of enzyme activities, is well known, we have compared in vitro maximum rates for the individual enzymes of urea synthesis with in vivo rates as judged by urea levels in blood of rats given large amounts of protein. The excellent agreement found between the calculated maximum activities from in vitro measurements to the time needed to metabolize a protein overload is presented and comments made on its significance and on the importance of maintaining protein intake at moderate levels, for the capacity of the urea system is limited. Since the intake of large quantities of protein increases the urea level in blood and in other tissues and since high urea levels are somewhat deleterious \"per se\" and particularly due to equilibrium with cyanate, ingestion of excessive amounts of protein is at best expensive and possibly hazardous.", "contents": "Correlation between in vivo and in vitro metabolic measurements. Maximum capacity for urea synthesis. Estimations of enzyme activity in vivo have been or can often only be done at unphysiological conditions. A main biochemical goal is to correlate in vivo and in vitro measurements. A possible approach to this problem is presented based on forcing metabolic activity in vivo to the maximum for a certain metabolic sequence. Since the urea synthesis system, including maximal rates of enzyme activities, is well known, we have compared in vitro maximum rates for the individual enzymes of urea synthesis with in vivo rates as judged by urea levels in blood of rats given large amounts of protein. The excellent agreement found between the calculated maximum activities from in vitro measurements to the time needed to metabolize a protein overload is presented and comments made on its significance and on the importance of maintaining protein intake at moderate levels, for the capacity of the urea system is limited. Since the intake of large quantities of protein increases the urea level in blood and in other tissues and since high urea levels are somewhat deleterious \"per se\" and particularly due to equilibrium with cyanate, ingestion of excessive amounts of protein is at best expensive and possibly hazardous."} {"id": "PMID:171689", "title": "NMR in cancer. VII. Sodium-23 magnetic resonance of normal and cancerous tissues.", "content": "Sodium-23 magnetic resonance was performed on four types of cancers and six types of normal tissues of rats and mice. The spin-lattice relaxation time of the tumors was generally longer than that of the normal tissues, with the most marked difference occurring between rat liver (T1 = 6.5 msec) and Novikoff hepatoma (T1 =23.7 msec). Estimation of tissue sodium from the signal intensity of the resonance indicated that all four types of tumors contained more sodium than any of the normal tissues.", "contents": "NMR in cancer. VII. Sodium-23 magnetic resonance of normal and cancerous tissues. Sodium-23 magnetic resonance was performed on four types of cancers and six types of normal tissues of rats and mice. The spin-lattice relaxation time of the tumors was generally longer than that of the normal tissues, with the most marked difference occurring between rat liver (T1 = 6.5 msec) and Novikoff hepatoma (T1 =23.7 msec). Estimation of tissue sodium from the signal intensity of the resonance indicated that all four types of tumors contained more sodium than any of the normal tissues."} {"id": "PMID:171685", "title": "Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions.", "content": "Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage after body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VHM lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggest a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.", "contents": "Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions. Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage after body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VHM lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggest a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested."} {"id": "PMID:171690", "title": "Characterization of nuclear and chromatin poly A-containing RNA.", "content": "Poly A-containing RNA was isolated from Novikoff hepatoma cell chromatin on nitrocellulose membrane filters after the cells were labeled with 32P-orthophosphate for 6 hours. Under denaturing conditions, the poly A-containing chromatin RNA had a sedimentation coefficient of approximately 8-18S. The presence of poly A tracts in the chromatin RNA fractions indicate that poly A addition occurs almost immediately after transcription. Poly A-containing chromatin RNA and nuclear RNA were approximately 1/5 as active as cytoplasmic poly A-containing RNA in the wheat germ translational system. Since chromatin poly A-containing RNA is the precursor of cytoplasmic poly A-containing RNA, further processing of this RNA prior to its attachment to polysomes may account for its increase in translational capacity.", "contents": "Characterization of nuclear and chromatin poly A-containing RNA. Poly A-containing RNA was isolated from Novikoff hepatoma cell chromatin on nitrocellulose membrane filters after the cells were labeled with 32P-orthophosphate for 6 hours. Under denaturing conditions, the poly A-containing chromatin RNA had a sedimentation coefficient of approximately 8-18S. The presence of poly A tracts in the chromatin RNA fractions indicate that poly A addition occurs almost immediately after transcription. Poly A-containing chromatin RNA and nuclear RNA were approximately 1/5 as active as cytoplasmic poly A-containing RNA in the wheat germ translational system. Since chromatin poly A-containing RNA is the precursor of cytoplasmic poly A-containing RNA, further processing of this RNA prior to its attachment to polysomes may account for its increase in translational capacity."} {"id": "PMID:171691", "title": "Stimulus-response coupling in neurohypophysial peptide target cells.", "content": "Recent data on the effects of neurohypophysial peptides at the cellular level are discussed with respect to the two basic processes involved in peptide hormone action--i.e., specific recognition of the information contained in the hormonal molecule and the transformation of this information into a stimulus leading to the final biological response. Four main aspects of this general problem are considered. A. Hormone-Receptor Interaction: Recent contributions in this field concern partial analysis of the three-dimensional conformation of oxytocin and vasopressin moleculal cells of the mammalian kidney. Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration. Models have been proposed that provide a valuable clue to the interpretation of structure-activity relationships among natural hormones and many structural analogues. Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney. B. Stimulus Generation: The nature of the primary stimulus generated by hormone-receptor interaction is still unknown. In the epithelial target cells of the amphibian skin and bladder and of the mammalian kidney, one of the first consequences of hormone-receptor interaction is the activation of membrane-bound adenylate cyclase. Analysis of the correlations between hormonal binding and adenylate cyclase activation suggests that activation is a function of receptor occupation rather than of the number of hormonal molecules interacting with the receptor per unit of time. On medullary adenylate cyclase of pig kidney, the relation between receptor occupancy and enzyme activation was found to be complex and nonlinear. The effects of several agents (calcium, nucleotides) on receptor occupancy and adenylate cyclase activation have been described. In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides.", "contents": "Stimulus-response coupling in neurohypophysial peptide target cells. Recent data on the effects of neurohypophysial peptides at the cellular level are discussed with respect to the two basic processes involved in peptide hormone action--i.e., specific recognition of the information contained in the hormonal molecule and the transformation of this information into a stimulus leading to the final biological response. Four main aspects of this general problem are considered. A. Hormone-Receptor Interaction: Recent contributions in this field concern partial analysis of the three-dimensional conformation of oxytocin and vasopressin moleculal cells of the mammalian kidney. Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration. Models have been proposed that provide a valuable clue to the interpretation of structure-activity relationships among natural hormones and many structural analogues. Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney. B. Stimulus Generation: The nature of the primary stimulus generated by hormone-receptor interaction is still unknown. In the epithelial target cells of the amphibian skin and bladder and of the mammalian kidney, one of the first consequences of hormone-receptor interaction is the activation of membrane-bound adenylate cyclase. Analysis of the correlations between hormonal binding and adenylate cyclase activation suggests that activation is a function of receptor occupation rather than of the number of hormonal molecules interacting with the receptor per unit of time. On medullary adenylate cyclase of pig kidney, the relation between receptor occupancy and enzyme activation was found to be complex and nonlinear. The effects of several agents (calcium, nucleotides) on receptor occupancy and adenylate cyclase activation have been described. In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides."} {"id": "PMID:171694", "title": "Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat.", "content": "Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.", "contents": "Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat. Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function."} {"id": "PMID:171695", "title": "Effects of promethazine on nocturnal sleep in normal man.", "content": "The effects of a phenothiazine, on sleep in ten healthy volunteers were investigated in two double blind polygraphic studies. The first part consisted of a single dose study with promethazine 50, 100, and 200 mg, using pentobarbital 100 mg as a reference substance. In the second part, four subjects spent 20 consecutive nights with nine drug nights (promethazine 100 mg), followed by a placebo withdrawal period of six nights, in the sleep laboratory. Promethazine showed a dose related REM-depressing effect with a greater decrease, the higher the dose. The placebo value was 20.7% REM of total sleep time and gave 16.3, 13.5 and 11.4 respectively, for promethazine 50, 100 and 200 mg. Pentobarbital gave 16.2% REM. There was also an increase of stage II and with the highest dose an increase of stage III + IV. An increase of REM-latency together with a decrease of REM-periods was also seen, and while pentobarbital gave a decrease in REM-density, promethazine did not cause any changes in the phasic REM-component. A REM-rebound was seen in the first night of withdrawal with an increase of per cent REM from 19.9%-25.1%. The mean for the whole withdrawal period was 23.1%. Promethazine in the highest dose, 200 mg, gave drowsiness and hangover effects in 14 nights out of 20. The REM-depressing effect of promethazine together with its relatively weak REM-rebound effect may explain its value in the treatment of withdrawal symptoms following abuse of alcohol and barbiturates.", "contents": "Effects of promethazine on nocturnal sleep in normal man. The effects of a phenothiazine, on sleep in ten healthy volunteers were investigated in two double blind polygraphic studies. The first part consisted of a single dose study with promethazine 50, 100, and 200 mg, using pentobarbital 100 mg as a reference substance. In the second part, four subjects spent 20 consecutive nights with nine drug nights (promethazine 100 mg), followed by a placebo withdrawal period of six nights, in the sleep laboratory. Promethazine showed a dose related REM-depressing effect with a greater decrease, the higher the dose. The placebo value was 20.7% REM of total sleep time and gave 16.3, 13.5 and 11.4 respectively, for promethazine 50, 100 and 200 mg. Pentobarbital gave 16.2% REM. There was also an increase of stage II and with the highest dose an increase of stage III + IV. An increase of REM-latency together with a decrease of REM-periods was also seen, and while pentobarbital gave a decrease in REM-density, promethazine did not cause any changes in the phasic REM-component. A REM-rebound was seen in the first night of withdrawal with an increase of per cent REM from 19.9%-25.1%. The mean for the whole withdrawal period was 23.1%. Promethazine in the highest dose, 200 mg, gave drowsiness and hangover effects in 14 nights out of 20. The REM-depressing effect of promethazine together with its relatively weak REM-rebound effect may explain its value in the treatment of withdrawal symptoms following abuse of alcohol and barbiturates."} {"id": "PMID:171709", "title": "Fluorometric and myothermic studies of cardiac energetics.", "content": "Energy production during isometric and isotonic contractions of cardiac muscle has been studied using the isolated papillary muscle of the rabbit at room temperature. Muscles were mounted on thermopiles to record heat production associated with small numbers of contractions and then were mounted in an organ bath for fluorometric recording of the level of reduction of mitochondrial NAD. After each twitch there was a decrease in the level of fluorescence followed by an exponential return to the resting level, or further decreases after subsequent twitches. The fluorescence-time integral (integral delta Fl-dt), or area enclosed by a fluorometric transient during and after a series of twitches, was found to vary in magnitude in a manner similar to the magnitude of the total heat production when the mechanical conditions of contraction were altered by varying the load. The influence of the metabolic state of the muscle was also studied by using either glucose or sodium pyruvate as the exogenous substrates in the bathing medium. When pyruvate was substituted for glucose, maximum external work, maximum isometric force, and maximum mechanical efficiency were all increased. The kinetics of oxidative recovery metabolism, either measured fluorometrically or derived from the heat production, was accelerated when pyruvate replaced glucose.", "contents": "Fluorometric and myothermic studies of cardiac energetics. Energy production during isometric and isotonic contractions of cardiac muscle has been studied using the isolated papillary muscle of the rabbit at room temperature. Muscles were mounted on thermopiles to record heat production associated with small numbers of contractions and then were mounted in an organ bath for fluorometric recording of the level of reduction of mitochondrial NAD. After each twitch there was a decrease in the level of fluorescence followed by an exponential return to the resting level, or further decreases after subsequent twitches. The fluorescence-time integral (integral delta Fl-dt), or area enclosed by a fluorometric transient during and after a series of twitches, was found to vary in magnitude in a manner similar to the magnitude of the total heat production when the mechanical conditions of contraction were altered by varying the load. The influence of the metabolic state of the muscle was also studied by using either glucose or sodium pyruvate as the exogenous substrates in the bathing medium. When pyruvate was substituted for glucose, maximum external work, maximum isometric force, and maximum mechanical efficiency were all increased. The kinetics of oxidative recovery metabolism, either measured fluorometrically or derived from the heat production, was accelerated when pyruvate replaced glucose."} {"id": "PMID:171710", "title": "Adenosine 3',5'-monophosphate, the myocardial cell membrane, and calcium.", "content": "Catecholamine-sensitive adenylate cyclase, cyclic nucleotide phosphodiesterase, adenosine 3', 5'-monophosphate (cyclic AMP)-dependent protein kinase, kinase substrate, and phosphoprotein phosphatase have variously been reported to be present in preparations of myocardial cellular membranes that function in the movement of Ca2+ in and out of the cell and in intracellular Ca2+ translocations, indicating that these membranees possess the equipment for the formation and destruction of cyclic Amp as well as for the initiation, effectuation, and termination of a possible membrane action of the nucleotide. It has also been observed that phosphorylation of seryl residues of protein in sarcolemma- and sarcotubule-rich myocardial subcellular fractions by cyclic AMP activated intrinsic and extrinsic protein kinases confers upon these membran structures an enhanced ability to bind or take up Ca2+ and that dibutyryl cyclic AMP, like adrenaline, produces in intact cardiac muscle simultaneous increases in contractile force and in the uptake of extracellular Ca2+. These findings are suggestive of a second messenger role of cyclic AMP in the beta-adrenoreceptor-mediated actions of catecholamines on myocardial contractile force and relaxation, in which Ca2+ would serve as a third messenger and be subject, respectively, to more effective removal from its binding sites on troponin. An alternative interpretation regards Ca2+ and cyclic AMP as interdependent twin second messengers in the catecholamine-induced inotropism. Since the physiological meaning of the reported effects of cyclic AMP on isolated myocardial membrane preparations is far from established an instances of a dissociation between the effects of catecholamines on myocardial contractile force and cyclic AMP levels have been observed, there is still room for hypotheses that relegate cyclic AMP to a nonobligatory, at most, supportive role in the action of the catecholamines on cardiac contraction.", "contents": "Adenosine 3',5'-monophosphate, the myocardial cell membrane, and calcium. Catecholamine-sensitive adenylate cyclase, cyclic nucleotide phosphodiesterase, adenosine 3', 5'-monophosphate (cyclic AMP)-dependent protein kinase, kinase substrate, and phosphoprotein phosphatase have variously been reported to be present in preparations of myocardial cellular membranes that function in the movement of Ca2+ in and out of the cell and in intracellular Ca2+ translocations, indicating that these membranees possess the equipment for the formation and destruction of cyclic Amp as well as for the initiation, effectuation, and termination of a possible membrane action of the nucleotide. It has also been observed that phosphorylation of seryl residues of protein in sarcolemma- and sarcotubule-rich myocardial subcellular fractions by cyclic AMP activated intrinsic and extrinsic protein kinases confers upon these membran structures an enhanced ability to bind or take up Ca2+ and that dibutyryl cyclic AMP, like adrenaline, produces in intact cardiac muscle simultaneous increases in contractile force and in the uptake of extracellular Ca2+. These findings are suggestive of a second messenger role of cyclic AMP in the beta-adrenoreceptor-mediated actions of catecholamines on myocardial contractile force and relaxation, in which Ca2+ would serve as a third messenger and be subject, respectively, to more effective removal from its binding sites on troponin. An alternative interpretation regards Ca2+ and cyclic AMP as interdependent twin second messengers in the catecholamine-induced inotropism. Since the physiological meaning of the reported effects of cyclic AMP on isolated myocardial membrane preparations is far from established an instances of a dissociation between the effects of catecholamines on myocardial contractile force and cyclic AMP levels have been observed, there is still room for hypotheses that relegate cyclic AMP to a nonobligatory, at most, supportive role in the action of the catecholamines on cardiac contraction."} {"id": "PMID:171711", "title": "The relationship between adenosine 3',5'-monophosphate levels and systolic transmembrane calcium flux.", "content": "The effects of inotropic agents on systolic transmembrane Ca++ flux were studied in isolated perfused guinea pig hearts depolarized with 22 mM K+. After depolarization, inotropic agents were added to the perfusion medium in an attempt to resotre excitability and contractions to the heart. Electrophysiological studies have shown that if excitability can be restored to the heart under these conditions, Ca++ carries the inward current of the action potential. Agents which putatively act by increasing intracellular levels of adenosine 3',5'-monophosphate (cyclic AMP) (isoproterenol, histamine, theophylline, papaverine, dibutyryl cyclic AMP) and Ca++ were found to restore excitability and contractions to K+-depolarized hearts. Threshold concentration for restoration by isoproterenol was 2 nM, and the strength of contractions developed by the restored heart were directly related to the dose of catecholamine used. Ca++ restoration was abolished by Ca++ antagonists (D 600, verapamil) but unaffected by beta blockade, whereas isoproterenol restoration was abolished by both. Ouabain, glucagon, and the divalent cation ionophore, A32187, failed to restore excitability to depolarized hearts. Correlative studies of tissue cyclic AMP levels were done. These data suggest that cyclic AMP can activate action potential-dependent Ca++ influx channels in myocardial cells.", "contents": "The relationship between adenosine 3',5'-monophosphate levels and systolic transmembrane calcium flux. The effects of inotropic agents on systolic transmembrane Ca++ flux were studied in isolated perfused guinea pig hearts depolarized with 22 mM K+. After depolarization, inotropic agents were added to the perfusion medium in an attempt to resotre excitability and contractions to the heart. Electrophysiological studies have shown that if excitability can be restored to the heart under these conditions, Ca++ carries the inward current of the action potential. Agents which putatively act by increasing intracellular levels of adenosine 3',5'-monophosphate (cyclic AMP) (isoproterenol, histamine, theophylline, papaverine, dibutyryl cyclic AMP) and Ca++ were found to restore excitability and contractions to K+-depolarized hearts. Threshold concentration for restoration by isoproterenol was 2 nM, and the strength of contractions developed by the restored heart were directly related to the dose of catecholamine used. Ca++ restoration was abolished by Ca++ antagonists (D 600, verapamil) but unaffected by beta blockade, whereas isoproterenol restoration was abolished by both. Ouabain, glucagon, and the divalent cation ionophore, A32187, failed to restore excitability to depolarized hearts. Correlative studies of tissue cyclic AMP levels were done. These data suggest that cyclic AMP can activate action potential-dependent Ca++ influx channels in myocardial cells."} {"id": "PMID:171712", "title": "Changes in the electroencephalogram and REM sleep time during morphine abstinence in pellet-implanted rats.", "content": "Rats were prepared with permanent electrodes for recording the electroencephalogram (EEG) and the electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hours later. The evaluation of continuous EEG and EMG recordings revealed a maximal reduction in the amount of REM sleep and a decline in its EEG voltage output during the first day after pellet removal. Both the duration of REM sleep and its mean integrated EEG voltage returned to the baseline levels by the second day of abstinence. A significant but short-lived REM rebound subsequently followed and was accompanied by a trend toward elevation of the mean EEG voltage. These changes are reminiscent of similar findings in rats withdrawn from morphine administered intravenously (Khazan and Colasanti, 1971, 1972). The smaller magnitude of changes in rats treated with morphine pellets, however, may suggest a lower degree of drug dependence.", "contents": "Changes in the electroencephalogram and REM sleep time during morphine abstinence in pellet-implanted rats. Rats were prepared with permanent electrodes for recording the electroencephalogram (EEG) and the electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hours later. The evaluation of continuous EEG and EMG recordings revealed a maximal reduction in the amount of REM sleep and a decline in its EEG voltage output during the first day after pellet removal. Both the duration of REM sleep and its mean integrated EEG voltage returned to the baseline levels by the second day of abstinence. A significant but short-lived REM rebound subsequently followed and was accompanied by a trend toward elevation of the mean EEG voltage. These changes are reminiscent of similar findings in rats withdrawn from morphine administered intravenously (Khazan and Colasanti, 1971, 1972). The smaller magnitude of changes in rats treated with morphine pellets, however, may suggest a lower degree of drug dependence."} {"id": "PMID:171715", "title": "[Future of endocrinology].", "content": "With regards to the future of endocrinology, the author displays a spectrum formed by the following \"hot\" subjects: A) From a research point of view: 1) Membrane and cytosomal molecular receptors. 2) Prohormones, with regards to: a) paraneoplastic and tumoral syndromes; and b) \"messenger\" or transitory hormones. 3) Metabolic clearings: a) Normal; b) in endocrine pathology and c) in pathology of transformation and elimination: liver and kidney. B) From a practical-empirical point of view: 1) Tests of fetoplacental function. 2) Clinical perspectives of the use of hormonal factors and provoked endocrinological clinics (iatrogenic endocrinology). 3) Growth factors and somatostatine. 4) Thymus hormones. 5) Gastrointestinal hormones. 6) The renine-angiotensine-aldrosterone system, the problems of hypertension and preservation of the hydric compartments. Natriuretic hormones.", "contents": "[Future of endocrinology]. With regards to the future of endocrinology, the author displays a spectrum formed by the following \"hot\" subjects: A) From a research point of view: 1) Membrane and cytosomal molecular receptors. 2) Prohormones, with regards to: a) paraneoplastic and tumoral syndromes; and b) \"messenger\" or transitory hormones. 3) Metabolic clearings: a) Normal; b) in endocrine pathology and c) in pathology of transformation and elimination: liver and kidney. B) From a practical-empirical point of view: 1) Tests of fetoplacental function. 2) Clinical perspectives of the use of hormonal factors and provoked endocrinological clinics (iatrogenic endocrinology). 3) Growth factors and somatostatine. 4) Thymus hormones. 5) Gastrointestinal hormones. 6) The renine-angiotensine-aldrosterone system, the problems of hypertension and preservation of the hydric compartments. Natriuretic hormones."} {"id": "PMID:171718", "title": "[Pneumological consultation practice in an anti-tuberculosis dispensary].", "content": "The authors present six years experience in connection with the diagnosis and the medical assistance of non-tuberculous broncho-pneumopathies in an anti-tuberculous dispensary. The data presented include 3600 cases with various diseases of which acute pneumopathies represent 11%, chronic bronchitis 14%, and broncho-pulmonary suppurations 9%. It is estimated that such an office of pneumological consultations within an anti-tuberculous dispensary is efficient and can, in the majority of the cases, make a correct diagnosis and provide corresponding dispensarization. This is conditioned by the existence of a nucleus for radiological, bacteriological and functional investigation.", "contents": "[Pneumological consultation practice in an anti-tuberculosis dispensary]. The authors present six years experience in connection with the diagnosis and the medical assistance of non-tuberculous broncho-pneumopathies in an anti-tuberculous dispensary. The data presented include 3600 cases with various diseases of which acute pneumopathies represent 11%, chronic bronchitis 14%, and broncho-pulmonary suppurations 9%. It is estimated that such an office of pneumological consultations within an anti-tuberculous dispensary is efficient and can, in the majority of the cases, make a correct diagnosis and provide corresponding dispensarization. This is conditioned by the existence of a nucleus for radiological, bacteriological and functional investigation."} {"id": "PMID:171719", "title": "[Circumstances concerning the diagnosis of tuberculosis in a pneumology department].", "content": "The analysis of a group of 67 patients hospitalized for various bronchopneumopathies, in whom evidencing of the tuberculosis bacilli led to the diagnosis of pulmonary tuberculosis allows to emphasize the increased efficiency of bacteriological detection by repeated bacilloscopy and successive cultures. They also stress the necessity of increased attention for pneumopathies that develop over the age of 50 years. The frequency of errors, predominantly stemming from the base network (territorial polyclinics), most of the confusion being made with suppurative broncho-pneumopathies, makes necessary the dispensarization of this category of patients in antituberculous units. The 56 new cases and the 11 cases in whom re-positivation was detected illustrate the possibilities of the bacteriological diagnosis and the contribution of a section of pneumology in the detection of pulmonary tuberculosis.", "contents": "[Circumstances concerning the diagnosis of tuberculosis in a pneumology department]. The analysis of a group of 67 patients hospitalized for various bronchopneumopathies, in whom evidencing of the tuberculosis bacilli led to the diagnosis of pulmonary tuberculosis allows to emphasize the increased efficiency of bacteriological detection by repeated bacilloscopy and successive cultures. They also stress the necessity of increased attention for pneumopathies that develop over the age of 50 years. The frequency of errors, predominantly stemming from the base network (territorial polyclinics), most of the confusion being made with suppurative broncho-pneumopathies, makes necessary the dispensarization of this category of patients in antituberculous units. The 56 new cases and the 11 cases in whom re-positivation was detected illustrate the possibilities of the bacteriological diagnosis and the contribution of a section of pneumology in the detection of pulmonary tuberculosis."} {"id": "PMID:171720", "title": "[Association of active pulmonary tuberculosis and pulmonary neoplasms].", "content": "Six cases are presented (out of a total of 11) with sputum positive pulmonary tuberculosis associated with bronchopulmonary carcinoma. The carcinoma developed during the evolution of 9 cases of active tuberculosis that had received a long discontinous treatment with tuberculostatic drugs. Only two of the 11 patients could be operated because the other 9 were hospitalized in the terminal stage of the disease, with invasive tumors. These had neither been suspected nor investigated for neoplasia. The use of all available means of investigation in the early stages of cancer can be of considerable help in the early detection of this disease and may allow for the application of surgical methods. Exploratory thoracotomy, together with extemporaneous histological investigation, are much more useful for the diagnosis than the expectative attitudes, which lead to theloss of the patient. Positive sputum should not eliminate the possibility of the association of tuberculosis with cancer.", "contents": "[Association of active pulmonary tuberculosis and pulmonary neoplasms]. Six cases are presented (out of a total of 11) with sputum positive pulmonary tuberculosis associated with bronchopulmonary carcinoma. The carcinoma developed during the evolution of 9 cases of active tuberculosis that had received a long discontinous treatment with tuberculostatic drugs. Only two of the 11 patients could be operated because the other 9 were hospitalized in the terminal stage of the disease, with invasive tumors. These had neither been suspected nor investigated for neoplasia. The use of all available means of investigation in the early stages of cancer can be of considerable help in the early detection of this disease and may allow for the application of surgical methods. Exploratory thoracotomy, together with extemporaneous histological investigation, are much more useful for the diagnosis than the expectative attitudes, which lead to theloss of the patient. Positive sputum should not eliminate the possibility of the association of tuberculosis with cancer."} {"id": "PMID:171721", "title": "[Renal complications after rifampicin].", "content": "Six observations are presented of patients receiving intermitent rifampicin treatment (900 mg twice weekly) that developed acute renal failure during treatment (4 cases) or when treatment was taken up again, after an interruption of 6 months (2 cases). Following anuria of 4--14 days and nitrogen retention between 248 and 521 mg, the evolution was favourable. Clinical, biological and immunological data (anti-rifampicin antibodies were detected in 1/8 and 1/16 in 3 cases) suggest the immune origin of this type of renal accidents.", "contents": "[Renal complications after rifampicin]. Six observations are presented of patients receiving intermitent rifampicin treatment (900 mg twice weekly) that developed acute renal failure during treatment (4 cases) or when treatment was taken up again, after an interruption of 6 months (2 cases). Following anuria of 4--14 days and nitrogen retention between 248 and 521 mg, the evolution was favourable. Clinical, biological and immunological data (anti-rifampicin antibodies were detected in 1/8 and 1/16 in 3 cases) suggest the immune origin of this type of renal accidents."} {"id": "PMID:171722", "title": "[2 cases of hemolytic complications during intermittent treatment with rifampicin].", "content": "Two cases are presented, of hemolytic jaundice, determined by rifampicin. The first occured in a woman in whom treatment was started again after an interruption of 6 months and the second in a man undergoing intermittent treatment that had been tolerated very well for 3 months. Following the extension of the application of rifampicin in intermittent treatment might occur more frequently. Posology apparently has a major role and some precautions are to be taken.", "contents": "[2 cases of hemolytic complications during intermittent treatment with rifampicin]. Two cases are presented, of hemolytic jaundice, determined by rifampicin. The first occured in a woman in whom treatment was started again after an interruption of 6 months and the second in a man undergoing intermittent treatment that had been tolerated very well for 3 months. Following the extension of the application of rifampicin in intermittent treatment might occur more frequently. Posology apparently has a major role and some precautions are to be taken."} {"id": "PMID:171727", "title": "[Adenitis following BCG vaccination].", "content": "The authors present a study on 167 cases of post-vaccinal adenitis after B.C.G. administration. These occured after the experimental application in 1,187 newborns of two vaccines produced by different laboratories. Manifest adenitis developed only after the application of the vaccine with a higher virulence and a significant concentration of live germs (A), while the vaccine with a low concentration of live germs only determined inflammatory adenitis (vaccine B). In the cases when vaccine A was applied, both after intra-dermal introduction of a 0,10 mg dose or of a 0,05 mg dose, it determined adenitis with a long evolution and in 7,79 percent, respectively in 6,95 percent of the vaccinated children fistulization occured. In most of the cases adenitis developed in the first 6 months following vaccination (86,77 percent) but in some cases it appeared even after 1-2 years. In 78,3 percent of the cases adenitis had a long course and in only 21,7 percent they regressed rapidly. Adenitis did not involve the general condition of the children but determined a concern of the parents. The duration of evolution of adenitis was, as a general rule, of several months, or 1-2 years and even longer and the treatment with tuberculostatics (INH) did not significantly alter their evolution. When there was a tendency to the formation of abscesses, especially in the case of gigantic adenitis, a reduction of the duration of the evolution was obtained by puncture, and especially by lymph-node curettage. The intensity of the post-vaccinal allergy is noted in cases complicated by adenitis (100 percent), as well as its long persistance, while in non-complicated cases the allergy diminished each year both in intensity and frequency. The authors recommend that before the mass use of a vaccine this should be tested, especially in young children, in view of making the correct choice of the efficient dose, with a maximal efficiency and the lowest number of complications.", "contents": "[Adenitis following BCG vaccination]. The authors present a study on 167 cases of post-vaccinal adenitis after B.C.G. administration. These occured after the experimental application in 1,187 newborns of two vaccines produced by different laboratories. Manifest adenitis developed only after the application of the vaccine with a higher virulence and a significant concentration of live germs (A), while the vaccine with a low concentration of live germs only determined inflammatory adenitis (vaccine B). In the cases when vaccine A was applied, both after intra-dermal introduction of a 0,10 mg dose or of a 0,05 mg dose, it determined adenitis with a long evolution and in 7,79 percent, respectively in 6,95 percent of the vaccinated children fistulization occured. In most of the cases adenitis developed in the first 6 months following vaccination (86,77 percent) but in some cases it appeared even after 1-2 years. In 78,3 percent of the cases adenitis had a long course and in only 21,7 percent they regressed rapidly. Adenitis did not involve the general condition of the children but determined a concern of the parents. The duration of evolution of adenitis was, as a general rule, of several months, or 1-2 years and even longer and the treatment with tuberculostatics (INH) did not significantly alter their evolution. When there was a tendency to the formation of abscesses, especially in the case of gigantic adenitis, a reduction of the duration of the evolution was obtained by puncture, and especially by lymph-node curettage. The intensity of the post-vaccinal allergy is noted in cases complicated by adenitis (100 percent), as well as its long persistance, while in non-complicated cases the allergy diminished each year both in intensity and frequency. The authors recommend that before the mass use of a vaccine this should be tested, especially in young children, in view of making the correct choice of the efficient dose, with a maximal efficiency and the lowest number of complications."} {"id": "PMID:171728", "title": "[Comparative study of spirographic values and scintigraphic aspects in patients with bronchopulmonary diseases].", "content": "A correlation was made of routine spyrographic data with the scintigraphic aspects of the lungs in 146, respectively 100 patients with bronchopulmonary diseases. The following conclusions can be inferred: 1) normal spirographic values do not necessarily reflect an integrity of the respiratory function. Besides these values pulmonary perfusion can be severily altered; 2) the more deteriorated the spirographic values the more probable will be the alteration of the pulmonary perfusion; 3) in the evaluation of the respiratory function one cannot base on the routine spirographic data if these are within normal limits, especially before pulmonary surgery is performed, or before the patients are resuming active life; according to possibilities, the scintigraphic investigation is to be performed.", "contents": "[Comparative study of spirographic values and scintigraphic aspects in patients with bronchopulmonary diseases]. A correlation was made of routine spyrographic data with the scintigraphic aspects of the lungs in 146, respectively 100 patients with bronchopulmonary diseases. The following conclusions can be inferred: 1) normal spirographic values do not necessarily reflect an integrity of the respiratory function. Besides these values pulmonary perfusion can be severily altered; 2) the more deteriorated the spirographic values the more probable will be the alteration of the pulmonary perfusion; 3) in the evaluation of the respiratory function one cannot base on the routine spirographic data if these are within normal limits, especially before pulmonary surgery is performed, or before the patients are resuming active life; according to possibilities, the scintigraphic investigation is to be performed."} {"id": "PMID:171729", "title": "[Incidence of chemical diabetes in non-specific bronchopneumopathies].", "content": "In the present conditions of industrial development and of urbanization encountered in our country clinico-statistical observations show that the risk of disease can be doubled by the increased incidence of diabetes and of bronchopneumopathies with common germs. The much higher incidence of the metabolic disturbance in the asymptomatic, as well as in the clinically manifest stages of bronchopulmonary suppurative diseases, as compared with tuberculosis demonstrate the more severe evolution, as well as the medico-social implications that tend to overtake, from the viewpoint of the severity, those known in pulmonary tuberculosis, which shows a continuous decline. The early detection of both diseases, which may prevent their association, complications or reciprocal aggravation, represent an imperative task.", "contents": "[Incidence of chemical diabetes in non-specific bronchopneumopathies]. In the present conditions of industrial development and of urbanization encountered in our country clinico-statistical observations show that the risk of disease can be doubled by the increased incidence of diabetes and of bronchopneumopathies with common germs. The much higher incidence of the metabolic disturbance in the asymptomatic, as well as in the clinically manifest stages of bronchopulmonary suppurative diseases, as compared with tuberculosis demonstrate the more severe evolution, as well as the medico-social implications that tend to overtake, from the viewpoint of the severity, those known in pulmonary tuberculosis, which shows a continuous decline. The early detection of both diseases, which may prevent their association, complications or reciprocal aggravation, represent an imperative task."} {"id": "PMID:171730", "title": "[Hyperchronic bronchopulmonary suppurations (clinical study of 100 cases)].", "content": "Following an analysis of the clinical observations files the authors present a series of aspects and clinical data, as well as functional results in connection with the evolution in out-bursts of 100 cases with bronchopulmonary suppurations dating for more than 10 years. These anatomo-clinical entities, developed either in healthy or on pre-existing lesions, of polymorphous aspect and frequently invalidating, with evident tendencies to relapses, determining considerable difficulties in the application of therapeutical measures, make necessary the dispensarization of patients and this must be organized in the frame of the network for pneumophthysiology, in view of providing the high quality assistance that is necessary in such cases.", "contents": "[Hyperchronic bronchopulmonary suppurations (clinical study of 100 cases)]. Following an analysis of the clinical observations files the authors present a series of aspects and clinical data, as well as functional results in connection with the evolution in out-bursts of 100 cases with bronchopulmonary suppurations dating for more than 10 years. These anatomo-clinical entities, developed either in healthy or on pre-existing lesions, of polymorphous aspect and frequently invalidating, with evident tendencies to relapses, determining considerable difficulties in the application of therapeutical measures, make necessary the dispensarization of patients and this must be organized in the frame of the network for pneumophthysiology, in view of providing the high quality assistance that is necessary in such cases."} {"id": "PMID:171735", "title": "[Model of eradication of tuberculosis in children in an area with high epidemiological potential].", "content": "In the territory of the Drajna TB dispensary, in the Prahova County, a series of complex measures have been experimented in the course of the second trimester of 1972, intending to prevent and to eliminate tuberculosis in children. Of the 31,731 children aged between 1 and 14 years, 29,496 have been tested with 2 units of PPD-IC65 (93 percent). A proportion of 12,6 percent of those tested presented reactions of more than 10 mm in diameter and 22,779 were vaccinated with BCG (Pasteur-Paris strain). The radiological pulmonary control of the reactors allowed for the detection of 24 cases of tuberculosis all of them new and asymptomatic. The efficiency of the detection was of 0,8 new cases per 1,000 tuberculin tested children or of 0,4 new cases per 100 of reactors that had been x-ray examined. This prophylactic action was repeated in 1973 in 2,219 children aged between 1 and 2-1/2 years that had been ommited in the preceding year and 4 new cases of tuberculosis were detected. In the medical districts in which there was a high prevalence of the children infection total radiophotographic case finding of the adult population was carried out. The result was a doubling of the TB incidence in children in 1972 followed by a 5-fold reduction of the indicators in 1973. The severe forms and death through tuberculosis in children have disappeared. The risk to develop the disease in BCG vaccinated children was reduced to 4,4 0/0000 per year. It is estimated that a generalization over the whole of the county of these prophylactic measures, as applied in the Drajna territory, under the form of a mass campaign, will allow for an improvement of the epidemiometric indicators in children in a relatively short time.", "contents": "[Model of eradication of tuberculosis in children in an area with high epidemiological potential]. In the territory of the Drajna TB dispensary, in the Prahova County, a series of complex measures have been experimented in the course of the second trimester of 1972, intending to prevent and to eliminate tuberculosis in children. Of the 31,731 children aged between 1 and 14 years, 29,496 have been tested with 2 units of PPD-IC65 (93 percent). A proportion of 12,6 percent of those tested presented reactions of more than 10 mm in diameter and 22,779 were vaccinated with BCG (Pasteur-Paris strain). The radiological pulmonary control of the reactors allowed for the detection of 24 cases of tuberculosis all of them new and asymptomatic. The efficiency of the detection was of 0,8 new cases per 1,000 tuberculin tested children or of 0,4 new cases per 100 of reactors that had been x-ray examined. This prophylactic action was repeated in 1973 in 2,219 children aged between 1 and 2-1/2 years that had been ommited in the preceding year and 4 new cases of tuberculosis were detected. In the medical districts in which there was a high prevalence of the children infection total radiophotographic case finding of the adult population was carried out. The result was a doubling of the TB incidence in children in 1972 followed by a 5-fold reduction of the indicators in 1973. The severe forms and death through tuberculosis in children have disappeared. The risk to develop the disease in BCG vaccinated children was reduced to 4,4 0/0000 per year. It is estimated that a generalization over the whole of the county of these prophylactic measures, as applied in the Drajna territory, under the form of a mass campaign, will allow for an improvement of the epidemiometric indicators in children in a relatively short time."} {"id": "PMID:171736", "title": "[Some epidemiological indicators in bronchopulmonary cancer in Sector 5 of Bucharest (study of 525 cases)].", "content": "The incidence was studied of broncho-pulmonary carcinoma, as well as of other epidemiological indicators in the 5th district of Bucharest over a period of 14 years (1960-1973) during which a total of 525 cases have occured. The incidence in this territory tends to become real from 1967 when the curve overtook the death-rate in the country. Following a continuous increase the number of cases reached 29 0/0000 in 1973 and it is presumed that it will attain 40 0/0000 in 1980. The increase in the morbidity is due to a higher number of cases noted in the extreme age groups (the increase was 2,5-fold in those under 40 years of age); the age group which was the most seriously involved was that between 60 and 69 years, in which the morbidity was of 111 0/0000. The proportion of women has also increased, from 1/6-th to 1/5-th of the total number of cases. In women the frequency of adenocarcinoma and of non-differentiated neoplasies is somewhat higher than in men. The proportion of histopathological confirmation of the disease diminished in the last years probably due to the higher number of aged subjects that cannot be correctly investigated or surgically treated.", "contents": "[Some epidemiological indicators in bronchopulmonary cancer in Sector 5 of Bucharest (study of 525 cases)]. The incidence was studied of broncho-pulmonary carcinoma, as well as of other epidemiological indicators in the 5th district of Bucharest over a period of 14 years (1960-1973) during which a total of 525 cases have occured. The incidence in this territory tends to become real from 1967 when the curve overtook the death-rate in the country. Following a continuous increase the number of cases reached 29 0/0000 in 1973 and it is presumed that it will attain 40 0/0000 in 1980. The increase in the morbidity is due to a higher number of cases noted in the extreme age groups (the increase was 2,5-fold in those under 40 years of age); the age group which was the most seriously involved was that between 60 and 69 years, in which the morbidity was of 111 0/0000. The proportion of women has also increased, from 1/6-th to 1/5-th of the total number of cases. In women the frequency of adenocarcinoma and of non-differentiated neoplasies is somewhat higher than in men. The proportion of histopathological confirmation of the disease diminished in the last years probably due to the higher number of aged subjects that cannot be correctly investigated or surgically treated."} {"id": "PMID:171737", "title": "[Radiophotographic and simultaneous bacteriological detection in an industrial group].", "content": "After carrying out a complex investigation of the workers of a confections factory the authors detected 2 new cases of tuberculosis (0,5 0/00), with the aid of radiophotography and another 2 cases (3,4 per 1000 subjects examined) by bacteriological investigation of the subjects that coughed. These last 2 cases were detected between those that had a normal thoracic aspect on the radiophotographic film alone. The observation of the authors allows to conclude that a bacteriological investigation of the suspects following radiophotography is not sufficient and that this type of investigation should be extended to certain groups of the population that show broncho-pulmonary symptoms. The association of the two methods, in well-defined technical and organisational conditions will allow for a significant increase of the efficiency of systematic examinations for the detection of pulmonary tuberculosis.", "contents": "[Radiophotographic and simultaneous bacteriological detection in an industrial group]. After carrying out a complex investigation of the workers of a confections factory the authors detected 2 new cases of tuberculosis (0,5 0/00), with the aid of radiophotography and another 2 cases (3,4 per 1000 subjects examined) by bacteriological investigation of the subjects that coughed. These last 2 cases were detected between those that had a normal thoracic aspect on the radiophotographic film alone. The observation of the authors allows to conclude that a bacteriological investigation of the suspects following radiophotography is not sufficient and that this type of investigation should be extended to certain groups of the population that show broncho-pulmonary symptoms. The association of the two methods, in well-defined technical and organisational conditions will allow for a significant increase of the efficiency of systematic examinations for the detection of pulmonary tuberculosis."} {"id": "PMID:171742", "title": "[Use and evaluation of radiophotography in the ambulatory care of lung diseases].", "content": "In the methodological cabinet for pneumology of the Institute of Phtysiology, radiophotography was employed in the following fields: a) screening of acute and chronic pneumopathies as appears from : the increase in the number of cases of non-specific pneumopathies as compared with cases of tuberculosis and the quantitative contribution of the method reflected in the fact that over 80% of the cases with non-specific pneumopathies were detected by radiophotography; b) diagnosis -- by comparing with the data recorded in the files, multiple incidences (front, posterior lordosis, profile); locally pointed (targeted) photographs, rf quantified functional tests in cases suspected of C.O.B.P.: c) follow-up of the evolution of dispensary cases and of the therapeutical effect; d) scientific research and teaching activities through epidemiological and pathogenesis studies, thus allowing for a valorification of the files over a 16 years period. The use of the radiophotographic method in the activity of a cabinet of pneumology is necessary especially because it allows for an early detection, a superior morphological diagnosis, as compared with radioscopy (fluoroscopy), for an objective and economical follow-up of the cases, providing at the same time material for scientific research and teaching demonstrations.", "contents": "[Use and evaluation of radiophotography in the ambulatory care of lung diseases]. In the methodological cabinet for pneumology of the Institute of Phtysiology, radiophotography was employed in the following fields: a) screening of acute and chronic pneumopathies as appears from : the increase in the number of cases of non-specific pneumopathies as compared with cases of tuberculosis and the quantitative contribution of the method reflected in the fact that over 80% of the cases with non-specific pneumopathies were detected by radiophotography; b) diagnosis -- by comparing with the data recorded in the files, multiple incidences (front, posterior lordosis, profile); locally pointed (targeted) photographs, rf quantified functional tests in cases suspected of C.O.B.P.: c) follow-up of the evolution of dispensary cases and of the therapeutical effect; d) scientific research and teaching activities through epidemiological and pathogenesis studies, thus allowing for a valorification of the files over a 16 years period. The use of the radiophotographic method in the activity of a cabinet of pneumology is necessary especially because it allows for an early detection, a superior morphological diagnosis, as compared with radioscopy (fluoroscopy), for an objective and economical follow-up of the cases, providing at the same time material for scientific research and teaching demonstrations."} {"id": "PMID:171743", "title": "[Organizational aspects and effectiveness of integral radiophotographic detection in a pilot area with an industrial profile].", "content": "Organizatoric and efficiency aspects are presented of five integral detections (the fifth presently in the final stage), carried out over a period of 14 years (1960--1973) in the territory of the anti-tuberculous dispensary of Turda. In the course of the four radiophotographic detections that have already been finally processed approximately 400.000 subjects have been examined. Mobilization was, in most of the cases, higher than 95% and the proportion of suspects was of 2--3.5%. The complex investigation of the suspects was higher than 95%. The index of detection of tuberculosis decreased severalfold (0.63% in the first investigation, 0.07% in the 4-th) when integral detections were repeated.", "contents": "[Organizational aspects and effectiveness of integral radiophotographic detection in a pilot area with an industrial profile]. Organizatoric and efficiency aspects are presented of five integral detections (the fifth presently in the final stage), carried out over a period of 14 years (1960--1973) in the territory of the anti-tuberculous dispensary of Turda. In the course of the four radiophotographic detections that have already been finally processed approximately 400.000 subjects have been examined. Mobilization was, in most of the cases, higher than 95% and the proportion of suspects was of 2--3.5%. The complex investigation of the suspects was higher than 95%. The index of detection of tuberculosis decreased severalfold (0.63% in the first investigation, 0.07% in the 4-th) when integral detections were repeated."} {"id": "PMID:171745", "title": "[Radiophotographic detection in evaluation of the incidence of tuberculosis].", "content": "In a territory with a population of over 120,000 inhabitants, of which 86% in rural environment, with a high tuberculosis endemic rate, four integral detections were organized in 12 districts and three in the other 12 base units of the area between 1969 and 1973. In most of the districts the incidences varied, in the years when integral detections were carried out the index being the double and in some cases 4-5 times higher, than in the years when this investigation was not performed. If annual incidences are computed for the entire area, excluding the cases detected by radiophotography the morbidity indexes appear by 50% lower. If for the whole territory anual incidences are calculated, excluding the cases that have been detected by radiophotography, morbidity indexes appear to be by 50% lower. From the viewpoint of the forms of disease radiophotographic detection brings to the dispensary two-thirds of the oligo- and asymptomatic cases. Subjects eliminating Koch bacilli, representing 44% of the patients that had been betected in a \"passive\" way, totalized 19% of the cases detected by radiophotography. The cost of detecting a new case was of 2210 lei and the costs for integral detections, related to the population of the area, represented less than one lei per inhabitant.", "contents": "[Radiophotographic detection in evaluation of the incidence of tuberculosis]. In a territory with a population of over 120,000 inhabitants, of which 86% in rural environment, with a high tuberculosis endemic rate, four integral detections were organized in 12 districts and three in the other 12 base units of the area between 1969 and 1973. In most of the districts the incidences varied, in the years when integral detections were carried out the index being the double and in some cases 4-5 times higher, than in the years when this investigation was not performed. If annual incidences are computed for the entire area, excluding the cases detected by radiophotography the morbidity indexes appear by 50% lower. If for the whole territory anual incidences are calculated, excluding the cases that have been detected by radiophotography, morbidity indexes appear to be by 50% lower. From the viewpoint of the forms of disease radiophotographic detection brings to the dispensary two-thirds of the oligo- and asymptomatic cases. Subjects eliminating Koch bacilli, representing 44% of the patients that had been betected in a \"passive\" way, totalized 19% of the cases detected by radiophotography. The cost of detecting a new case was of 2210 lei and the costs for integral detections, related to the population of the area, represented less than one lei per inhabitant."} {"id": "PMID:171744", "title": "[Comparative results of total detections and detection in a group of patients with high risk for tuberculosis in an urban environment].", "content": "In the territory of 5 anti-TBC dispensaries in the area of Bucharest 2 circumscriptions have been selected at random in which radiophotographic detection was to be carried out integrally and 2 other circumscriptions were selected for the investigation of groups at high risk of developing tuberculosis. All the new cases of active pulmonary tuberculosis that have been recorded, through all the methods in these 20 circumscriptions in 1973 were analized retrospectively and the reasons appeared that had determined their existence was mentioned or was ommitted on the occasion of previous investigations. These reasons were correlated with the data concerning the method for detection that had been employed, according to the indications of the tuberculosis dispensaries. In view of the evaluation of the degree of real covering of the population in integral rf investigations, the team of the Institute of Phtysiology investigated representative lots of population from each dispensary and checked the catagraphy of the population in the field, house-by-house. It was noted that 20--21% of the subjects that had been programmed for the integral rf examination (according to catagraphic criteria) were absent when the checking in the field, that should have been programmed, were not included in the catagraphy. On the basis of this study the methodology for radiophotographic detection for groups with risk of developing tuberculosis was established.", "contents": "[Comparative results of total detections and detection in a group of patients with high risk for tuberculosis in an urban environment]. In the territory of 5 anti-TBC dispensaries in the area of Bucharest 2 circumscriptions have been selected at random in which radiophotographic detection was to be carried out integrally and 2 other circumscriptions were selected for the investigation of groups at high risk of developing tuberculosis. All the new cases of active pulmonary tuberculosis that have been recorded, through all the methods in these 20 circumscriptions in 1973 were analized retrospectively and the reasons appeared that had determined their existence was mentioned or was ommitted on the occasion of previous investigations. These reasons were correlated with the data concerning the method for detection that had been employed, according to the indications of the tuberculosis dispensaries. In view of the evaluation of the degree of real covering of the population in integral rf investigations, the team of the Institute of Phtysiology investigated representative lots of population from each dispensary and checked the catagraphy of the population in the field, house-by-house. It was noted that 20--21% of the subjects that had been programmed for the integral rf examination (according to catagraphic criteria) were absent when the checking in the field, that should have been programmed, were not included in the catagraphy. On the basis of this study the methodology for radiophotographic detection for groups with risk of developing tuberculosis was established."} {"id": "PMID:171746", "title": "[Long-term study of the effect of successive surveys on tuberculosis endemia].", "content": "A whole rural population of 16359 subjects was followed for a period of 24 years. This period of 24 years is well divided from the viewpoint of the succesive systematic detection three intervals being selected, as follows: a) the stage of usual anti-tuberculous assistance; b) the stage of scientific experimentation consisting in 3 radiophotographic detections repeated every two years and the annual control of groups with high risk, between 1960--1965, completed by integral biological detection in children (every year) and bacteriological controls. The population controls were followed by the diagnosis; c) the stage of discontinuing the experiment when current antituberculous assistance was resumed, between 1966 and 1974. All cases of active pulmonary tuberculosis, that have been recorded through all the methods of investigation over a period of 24 years in all these localities are correlated, on the one hand to one another, and on the other hand with objective documents obtained during the period of intensive control of the population over the 6-years interval. Thus the limits appear more correctly, within which this natural history of the disease can be detected through various types of population control, as well as some practical consequences for the improvement of the technique and of the control methodology in the future.", "contents": "[Long-term study of the effect of successive surveys on tuberculosis endemia]. A whole rural population of 16359 subjects was followed for a period of 24 years. This period of 24 years is well divided from the viewpoint of the succesive systematic detection three intervals being selected, as follows: a) the stage of usual anti-tuberculous assistance; b) the stage of scientific experimentation consisting in 3 radiophotographic detections repeated every two years and the annual control of groups with high risk, between 1960--1965, completed by integral biological detection in children (every year) and bacteriological controls. The population controls were followed by the diagnosis; c) the stage of discontinuing the experiment when current antituberculous assistance was resumed, between 1966 and 1974. All cases of active pulmonary tuberculosis, that have been recorded through all the methods of investigation over a period of 24 years in all these localities are correlated, on the one hand to one another, and on the other hand with objective documents obtained during the period of intensive control of the population over the 6-years interval. Thus the limits appear more correctly, within which this natural history of the disease can be detected through various types of population control, as well as some practical consequences for the improvement of the technique and of the control methodology in the future."} {"id": "PMID:171747", "title": "[20 years of experience in the use of radiophotography in the prevention of tuberculosis].", "content": "Based on a 20 years experience in the application of the pulmonary radiological control relying on radiophotography, the authors reached the following conclusions: -- 40% of subjects considered as suspect following radiophotography were confirmed to have pathological thoracic changes of which 8.5% with acitve pulmonary tuberculosis; in 1954 60% new cases were detected with 73% early forms of the disease and in 1973, 85% of new cases with 90% early forms of the disease; the effects of annual integral radiophotographic defection, correlated with other forms of anti-tuberculous fight, can be expressed in the following morbidity data : in 1954 -- 1.400.000 ; in 1956 -- 870.000 ; in 1957 -- 300.000 ; in 1962 -- 170.000 ; in 1963 -- 80.000 ; in 1966 -- 50.000. This last figure was maintained until 1969, two small increases being noted in the following two years (1970 and 1971). In the last year (1973) the figure was 40.000.", "contents": "[20 years of experience in the use of radiophotography in the prevention of tuberculosis]. Based on a 20 years experience in the application of the pulmonary radiological control relying on radiophotography, the authors reached the following conclusions: -- 40% of subjects considered as suspect following radiophotography were confirmed to have pathological thoracic changes of which 8.5% with acitve pulmonary tuberculosis; in 1954 60% new cases were detected with 73% early forms of the disease and in 1973, 85% of new cases with 90% early forms of the disease; the effects of annual integral radiophotographic defection, correlated with other forms of anti-tuberculous fight, can be expressed in the following morbidity data : in 1954 -- 1.400.000 ; in 1956 -- 870.000 ; in 1957 -- 300.000 ; in 1962 -- 170.000 ; in 1963 -- 80.000 ; in 1966 -- 50.000. This last figure was maintained until 1969, two small increases being noted in the following two years (1970 and 1971). In the last year (1973) the figure was 40.000."} {"id": "PMID:171748", "title": "[Contribution of radiophotography in the knowledge and control of tuberculosis endemia in the area of an anti-tubercular dispensary].", "content": "After three integral detections the index of detection of active cases fell from 3.360/00 -- at the first one -- to 0.500/00 -- at the third, while the dynamics of the incidence of tuberculosis decreased in the same period from 130,950/0000 to 53.950/0000. Radiophotography brought to the anti-tuberculous dispensary 86.130/0 of the cases with pulmonary tuberculosis.", "contents": "[Contribution of radiophotography in the knowledge and control of tuberculosis endemia in the area of an anti-tubercular dispensary]. After three integral detections the index of detection of active cases fell from 3.360/00 -- at the first one -- to 0.500/00 -- at the third, while the dynamics of the incidence of tuberculosis decreased in the same period from 130,950/0000 to 53.950/0000. Radiophotography brought to the anti-tuberculous dispensary 86.130/0 of the cases with pulmonary tuberculosis."} {"id": "PMID:171749", "title": "[3 successive radiophotographic surveys in a rural territory].", "content": "Three detections, carried out over a period of two years gave the following results: a high rate was obtained in the first one while the following two gave lower rates, in parallel with a decrease of the overall incidence through pulmonary tuberculosis from 326.70/0000 in 1968 to 1440/0000 in 1973. The cases were recently detected, during the last two investigations, which allowed for a wider application of the ambulatory treatment, a fact that compensated from the financial view point the cost of radiophotographic investigations. The authors suggest the maintenance of integral detection, with the same periodicity in the rural environment.", "contents": "[3 successive radiophotographic surveys in a rural territory]. Three detections, carried out over a period of two years gave the following results: a high rate was obtained in the first one while the following two gave lower rates, in parallel with a decrease of the overall incidence through pulmonary tuberculosis from 326.70/0000 in 1968 to 1440/0000 in 1973. The cases were recently detected, during the last two investigations, which allowed for a wider application of the ambulatory treatment, a fact that compensated from the financial view point the cost of radiophotographic investigations. The authors suggest the maintenance of integral detection, with the same periodicity in the rural environment."} {"id": "PMID:171750", "title": "[Pulmonary tuberculosis discovered by methods other than radiophotography].", "content": "The retrospective analysis of the investigations carried out between 1969 and 1973 showed that for a total of 323 new cases of tuberculosis of the lungs recorded over this period of five years, 279 (86.37%) had been detected through radiophotography, while the remaining 13.63% were detected by other methods. Of these 67.74% were primary infection cases of tuberculosis and 32.53% were secondary tuberculosis. None of the newly discovered adults had been examined by radiophotography before (their absences were either motivated or not). Thus the cases discovered between the detections do not represent a failure of the radiophotographic method.", "contents": "[Pulmonary tuberculosis discovered by methods other than radiophotography]. The retrospective analysis of the investigations carried out between 1969 and 1973 showed that for a total of 323 new cases of tuberculosis of the lungs recorded over this period of five years, 279 (86.37%) had been detected through radiophotography, while the remaining 13.63% were detected by other methods. Of these 67.74% were primary infection cases of tuberculosis and 32.53% were secondary tuberculosis. None of the newly discovered adults had been examined by radiophotography before (their absences were either motivated or not). Thus the cases discovered between the detections do not represent a failure of the radiophotographic method."} {"id": "PMID:171751", "title": "[Is asymptomatic pulmonary tuberculosis ever detected by radiophotography?].", "content": "Following several organized detection campaigns it was demonstrated that these did not provide valid results even when these were organized as integral detections or for groups at risk. The authors maintain that the only group in which a satisfactory result can be obtained is represented by the subjects showing symptoms evoking pulmonary tuberculosis. These are known and can be sent to investigation by the district physician. It is recommended that the radiophotographic equipments should be assimilated to radiological apparatuses, but with better accesibility which the physicians should be able to apply without difficulty in the cases with major or minor symptoms suggesting specifical pulmonary disease.", "contents": "[Is asymptomatic pulmonary tuberculosis ever detected by radiophotography?]. Following several organized detection campaigns it was demonstrated that these did not provide valid results even when these were organized as integral detections or for groups at risk. The authors maintain that the only group in which a satisfactory result can be obtained is represented by the subjects showing symptoms evoking pulmonary tuberculosis. These are known and can be sent to investigation by the district physician. It is recommended that the radiophotographic equipments should be assimilated to radiological apparatuses, but with better accesibility which the physicians should be able to apply without difficulty in the cases with major or minor symptoms suggesting specifical pulmonary disease."} {"id": "PMID:171752", "title": "[Some tactical trends in radiophotographic detection].", "content": "The efficiency of organized detections in an area with low phtysiogenic potential fell progressively over the last five years while the efficiency of spontaneous detections rose significantly in patients with apparently non-specific respiratory symptoms. In the districts with low incidence radiophotographic actions were not very frequent and the covering of the whole population was rather low. In contrast good results were obtained in the general network in connection with subjects with respiratory symptoms. For the districts with high endemics integral detection is recommended.", "contents": "[Some tactical trends in radiophotographic detection]. The efficiency of organized detections in an area with low phtysiogenic potential fell progressively over the last five years while the efficiency of spontaneous detections rose significantly in patients with apparently non-specific respiratory symptoms. In the districts with low incidence radiophotographic actions were not very frequent and the covering of the whole population was rather low. In contrast good results were obtained in the general network in connection with subjects with respiratory symptoms. For the districts with high endemics integral detection is recommended."} {"id": "PMID:171758", "title": "Lymphographic aspects of the barrier function of lymph nodes in Hodgkin's disease.", "content": "The persistence of Lipiodol in various lymph node groups was followed up by systematic lymphographic control. Assuming a certain relationship between the barrier function of the lymph nodes and the persistence of their image on the film the authors have tried to find out whether the duration of Lipiodol persistence may be a test for the estimation of prognosis in Hodgkin's disease. The observation of such cases has shown that Lipiodol is retained for a longer period in the external iliac and lombo-aortic lymph nodes as well as in the pathologic ones, except those with lymphocyte depletion, whereas it is very rapidly eliminated from the inguinal nodes. These findings seem to prove that Hodgkin's disease is more severe in patients in whom the barrier function of the lymph nodes is defective i.e. unable to retain the foreign substances introduced in the organism. These conclusions should be further verified by comparison with other clinical and biologic factors.", "contents": "Lymphographic aspects of the barrier function of lymph nodes in Hodgkin's disease. The persistence of Lipiodol in various lymph node groups was followed up by systematic lymphographic control. Assuming a certain relationship between the barrier function of the lymph nodes and the persistence of their image on the film the authors have tried to find out whether the duration of Lipiodol persistence may be a test for the estimation of prognosis in Hodgkin's disease. The observation of such cases has shown that Lipiodol is retained for a longer period in the external iliac and lombo-aortic lymph nodes as well as in the pathologic ones, except those with lymphocyte depletion, whereas it is very rapidly eliminated from the inguinal nodes. These findings seem to prove that Hodgkin's disease is more severe in patients in whom the barrier function of the lymph nodes is defective i.e. unable to retain the foreign substances introduced in the organism. These conclusions should be further verified by comparison with other clinical and biologic factors."} {"id": "PMID:171753", "title": "[Combination of radiophotographic and tuberculin detection in groups of young people].", "content": "Tuberculin pre-testing between 1971 and 1973 in profesional schools, as well as in high schools from Brasov, showed that by the radiophotographic examination of tuberculin reactors only, all the new cases of tuberculosis were detected, as well as those requiring surveillance and chemoprophylaxis. In this way over one half of the adolescents from professional schools and one quarter of those from high schools could be excepted from radiophotography, with the corresponding effects of radiation prevention and economic efficiency.", "contents": "[Combination of radiophotographic and tuberculin detection in groups of young people]. Tuberculin pre-testing between 1971 and 1973 in profesional schools, as well as in high schools from Brasov, showed that by the radiophotographic examination of tuberculin reactors only, all the new cases of tuberculosis were detected, as well as those requiring surveillance and chemoprophylaxis. In this way over one half of the adolescents from professional schools and one quarter of those from high schools could be excepted from radiophotography, with the corresponding effects of radiation prevention and economic efficiency."} {"id": "PMID:171754", "title": "[Indices of detection in integral radiophotographic examinations in rural areas].", "content": "Integral radiophotographic detection was carried out in the territories of 5 randomly selected village dispensaries in 5 different counties. The action was performed in strictly operational conditions, without external experimental interferences. Stress was laid on the strict following of the methodological letter concerning radiophotography. The performing of integral radiophotographic detection in strictly operational conditions in the rural environment demonstrated the utility of these examinations in the present stage. The output obtained can be considered as satisfactory; local variations can be noted and this indicates the possibility of differentiating the conduct in various geographical areas.", "contents": "[Indices of detection in integral radiophotographic examinations in rural areas]. Integral radiophotographic detection was carried out in the territories of 5 randomly selected village dispensaries in 5 different counties. The action was performed in strictly operational conditions, without external experimental interferences. Stress was laid on the strict following of the methodological letter concerning radiophotography. The performing of integral radiophotographic detection in strictly operational conditions in the rural environment demonstrated the utility of these examinations in the present stage. The output obtained can be considered as satisfactory; local variations can be noted and this indicates the possibility of differentiating the conduct in various geographical areas."} {"id": "PMID:171755", "title": "[Medical radiophotography in the activities of rural polyclinics].", "content": "The county polyclinic provides the radiophotographic control of a rural population of 122.741 inhabitants from the area surrounding the capital city of Bucharest. Of the total number of cases of pulmonary tuberculoses that have been recorded only 16,6% were detected in the fixed center and 61,8% by integral detections, carried out by the radiophotographic caravans. That is why the authors consider that this is not the right time to abandon integral detection. The fixed centers, by performing examinations in all those entering new jobs detect cases of tuberculosis belonging to other geographical areas. Thus, of 235 cases detected over a period of 3 years, 67% belonged to other territories and only 33% were from the population normally covered by the center. This is the filter role played by fixed centers carrying out radiophotographic detection. As compared with the 235 cases of tuberculosis there were 399 cases of non-tuberculous pulmonary diseases.", "contents": "[Medical radiophotography in the activities of rural polyclinics]. The county polyclinic provides the radiophotographic control of a rural population of 122.741 inhabitants from the area surrounding the capital city of Bucharest. Of the total number of cases of pulmonary tuberculoses that have been recorded only 16,6% were detected in the fixed center and 61,8% by integral detections, carried out by the radiophotographic caravans. That is why the authors consider that this is not the right time to abandon integral detection. The fixed centers, by performing examinations in all those entering new jobs detect cases of tuberculosis belonging to other geographical areas. Thus, of 235 cases detected over a period of 3 years, 67% belonged to other territories and only 33% were from the population normally covered by the center. This is the filter role played by fixed centers carrying out radiophotographic detection. As compared with the 235 cases of tuberculosis there were 399 cases of non-tuberculous pulmonary diseases."} {"id": "PMID:171756", "title": "[Retrospective study of the value of radiophotographic examinations in the detection of pulmonary cancer].", "content": "Out of a total of 123 cases of centro-hilar pulmonary carcinoma and of 65 cases of carcinoma with peripheral localization changes on the previous radiophotographic images were found in 54% of the cases. The time necessary for doubling of the tumour size was of 22 months for the peripheral forms of cancer. The suspicion of pulmonary cancer was mentioned in the radiophotographic register two years before the diagnosis of the disease was made.", "contents": "[Retrospective study of the value of radiophotographic examinations in the detection of pulmonary cancer]. Out of a total of 123 cases of centro-hilar pulmonary carcinoma and of 65 cases of carcinoma with peripheral localization changes on the previous radiophotographic images were found in 54% of the cases. The time necessary for doubling of the tumour size was of 22 months for the peripheral forms of cancer. The suspicion of pulmonary cancer was mentioned in the radiophotographic register two years before the diagnosis of the disease was made."} {"id": "PMID:171762", "title": "Studies on human serum high-density lipoproteins (HDL). IV. Isolation of lipoprotein families after incubation of HDL.", "content": "The high-density lipoproteins (HDL) of human serum appear to be unstable and easily exposed to chemical changes during isolation. In earlier studies we have isolated and purified HDL subfractions either in the presence of an SH-blocking agent, DTNB, or in the cold. By both procedures reproducible lipoprotein subfractions could be recovered by hydroxyl apatite column chromatography at the elution steps 0.03-0.05 mol/l (subfraction II) and 0.05-0.15 mol/l phosphate buffer (subfraction III). The protein moiety of both lipoprotein subfractions contained polypeptides A-I , A-II, thin line (TL), C-I and C-II, and the protein moiety of subfraction III contained also C-III. The incubation at 37 degrees C of these HDL subfractions gave reproducible daughter lipoprotein fractions that could be recovered by subsequent rechromatography on hydroxyl apatite. At each of the elution steps 0.05-0.075 mol/l and 0.075-0. mol/l one daughter fraction was recovered, the protein moiety of which was composed of polypeptide A-I, as judged by polyacrylamide gel electrophoresis, immunodiffusion, and amino acid analysis. The incubation of parent subfractions II and III caused also the appearance at elution step 0.001-0.01 mol/l of a daughter lipoprotein fraction - lipoprotein A (Lp-A) - that was characterized by a protein moiety with polypeptides A-I and A-II in equal amounts. The 'release' of lipoprotein A-I (Lp-A-I) and Lp-A was shown to be due rather to the incubation than to the column chromatography as such. The chemical changes occurring during the incubation of HDL suggested a degradation of phosphatidylcholine (PC) to lysophosphatidylcholine (lyso-PC) and glycerylphosphorylcholine (GPC). It is suggested that the degradation of PC might interfere with the interaction between the lipoprotein families composing HDL.", "contents": "Studies on human serum high-density lipoproteins (HDL). IV. Isolation of lipoprotein families after incubation of HDL. The high-density lipoproteins (HDL) of human serum appear to be unstable and easily exposed to chemical changes during isolation. In earlier studies we have isolated and purified HDL subfractions either in the presence of an SH-blocking agent, DTNB, or in the cold. By both procedures reproducible lipoprotein subfractions could be recovered by hydroxyl apatite column chromatography at the elution steps 0.03-0.05 mol/l (subfraction II) and 0.05-0.15 mol/l phosphate buffer (subfraction III). The protein moiety of both lipoprotein subfractions contained polypeptides A-I , A-II, thin line (TL), C-I and C-II, and the protein moiety of subfraction III contained also C-III. The incubation at 37 degrees C of these HDL subfractions gave reproducible daughter lipoprotein fractions that could be recovered by subsequent rechromatography on hydroxyl apatite. At each of the elution steps 0.05-0.075 mol/l and 0.075-0. mol/l one daughter fraction was recovered, the protein moiety of which was composed of polypeptide A-I, as judged by polyacrylamide gel electrophoresis, immunodiffusion, and amino acid analysis. The incubation of parent subfractions II and III caused also the appearance at elution step 0.001-0.01 mol/l of a daughter lipoprotein fraction - lipoprotein A (Lp-A) - that was characterized by a protein moiety with polypeptides A-I and A-II in equal amounts. The 'release' of lipoprotein A-I (Lp-A-I) and Lp-A was shown to be due rather to the incubation than to the column chromatography as such. The chemical changes occurring during the incubation of HDL suggested a degradation of phosphatidylcholine (PC) to lysophosphatidylcholine (lyso-PC) and glycerylphosphorylcholine (GPC). It is suggested that the degradation of PC might interfere with the interaction between the lipoprotein families composing HDL."} {"id": "PMID:171757", "title": "[Contribution of medical radiophotography in detection of non-tubercular intrathoracic diseases].", "content": "Concomittantly with the reduction of the tuberculous processes and with the transfer of the patients to pneumology sections radiophotographical detection of other pulmonary diseases has become more important. From the control of suspects the following data could be obtained: 8.5% cases of active tuberculosis, 21.46% cases with minimal lesions and with sequellae, 7,2% non-specific pneumopathies, 1.10% cardiovascular patients, 0.23% pleuro-pulmonary tumours and 0.51% cases with other affections.", "contents": "[Contribution of medical radiophotography in detection of non-tubercular intrathoracic diseases]. Concomittantly with the reduction of the tuberculous processes and with the transfer of the patients to pneumology sections radiophotographical detection of other pulmonary diseases has become more important. From the control of suspects the following data could be obtained: 8.5% cases of active tuberculosis, 21.46% cases with minimal lesions and with sequellae, 7,2% non-specific pneumopathies, 1.10% cardiovascular patients, 0.23% pleuro-pulmonary tumours and 0.51% cases with other affections."} {"id": "PMID:171767", "title": "Organophosphorus and methyl carbamate insecticide teratogenesis: diminished NAD in chicken embryos.", "content": "Studies with 36 organophosphorus and 12 methyl carbamate compounds establish a correlation between reduction in nicotinamide adenine dinucleotide (NAD) levels and severity of teratogenic signs in chicken embryos, a relation supported by reversal of these effects by nicotinamide derivatives. Diminished NAD occurring at organophosphorus and methyl carbamate concentrations as low as 0.6 to 2.0 parts per million in the egg constitutes a newly recognized biochemical lesion induced by the two most important classes of insecticide chemicals.", "contents": "Organophosphorus and methyl carbamate insecticide teratogenesis: diminished NAD in chicken embryos. Studies with 36 organophosphorus and 12 methyl carbamate compounds establish a correlation between reduction in nicotinamide adenine dinucleotide (NAD) levels and severity of teratogenic signs in chicken embryos, a relation supported by reversal of these effects by nicotinamide derivatives. Diminished NAD occurring at organophosphorus and methyl carbamate concentrations as low as 0.6 to 2.0 parts per million in the egg constitutes a newly recognized biochemical lesion induced by the two most important classes of insecticide chemicals."} {"id": "PMID:171768", "title": "In vitro demonstration of an endothelial proliferative factor produced by neural cell lines.", "content": "Cultured endothelial cells exhibit a six- to tenfold increase in thymidine labeling index in response to a soluble factor elaborated by clonal cell lines of neural origin. This factor, endothelial proliferation factor, appears to be a unique property of tumor cells and may mediate the vascularization of these neoplasms.", "contents": "In vitro demonstration of an endothelial proliferative factor produced by neural cell lines. Cultured endothelial cells exhibit a six- to tenfold increase in thymidine labeling index in response to a soluble factor elaborated by clonal cell lines of neural origin. This factor, endothelial proliferation factor, appears to be a unique property of tumor cells and may mediate the vascularization of these neoplasms."} {"id": "PMID:171769", "title": "Production of globules in mouse L cells penetrated with hamster sperms.", "content": "Globule formation has been observed in long-term cultures of mouse L cells penetrated with hamster spermatozoa. These numerous, uniform, and spherical structures are approximately 10 micrometers in diameter when formed, and are positive to stains specific for proteins and nucleic acids. They may be produced either by sperms within their target cells or by the cells in response to penetration by the spermatozoa.", "contents": "Production of globules in mouse L cells penetrated with hamster sperms. Globule formation has been observed in long-term cultures of mouse L cells penetrated with hamster spermatozoa. These numerous, uniform, and spherical structures are approximately 10 micrometers in diameter when formed, and are positive to stains specific for proteins and nucleic acids. They may be produced either by sperms within their target cells or by the cells in response to penetration by the spermatozoa."} {"id": "PMID:171770", "title": "Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth.", "content": "Dibutyryl cyclic adenosine 3',5'-monophosphate (cyclic AMP) produces phosphodiesterase induction, growth arrest, and cytolysis in S49 lymphoma cells. The striking parallelism between protein kinase activity that is dependent on cytosol cyclic AMP and cellular responses to dibutyryl cyclic AMP in wild-type cells and three classes of clones resistant to cyclic AMP indicates that protein kinase mediates cyclic AMP regulation of growth and enzyme induction in S49 cells.", "contents": "Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth. Dibutyryl cyclic adenosine 3',5'-monophosphate (cyclic AMP) produces phosphodiesterase induction, growth arrest, and cytolysis in S49 lymphoma cells. The striking parallelism between protein kinase activity that is dependent on cytosol cyclic AMP and cellular responses to dibutyryl cyclic AMP in wild-type cells and three classes of clones resistant to cyclic AMP indicates that protein kinase mediates cyclic AMP regulation of growth and enzyme induction in S49 cells."} {"id": "PMID:171772", "title": "Phosphoribosylpyrophosphate overproduction, a new metabolic abnormality in the Lesch Nyhan syndrome.", "content": "The activity of phosphoribosylpyrophosphate synthetase and the rate of phosphoribosylpyrophosphate accumulation are significantly increased in cultured lymphocytes of Lesch Nyhan patients deficient in hypoxanthine guanine phosphoribosyltransferase and in a clone of mutagen-induced, hypoxanthine guanine phosphoribosyltransferase deficient human lymphocytes. The increase in phosphoribosylpyrophosphate synthetase activity is the cause of the abnormally high cellular phosphoribosylpyrophosphate content and possibly of the purine overproduction described in this syndrome.", "contents": "Phosphoribosylpyrophosphate overproduction, a new metabolic abnormality in the Lesch Nyhan syndrome. The activity of phosphoribosylpyrophosphate synthetase and the rate of phosphoribosylpyrophosphate accumulation are significantly increased in cultured lymphocytes of Lesch Nyhan patients deficient in hypoxanthine guanine phosphoribosyltransferase and in a clone of mutagen-induced, hypoxanthine guanine phosphoribosyltransferase deficient human lymphocytes. The increase in phosphoribosylpyrophosphate synthetase activity is the cause of the abnormally high cellular phosphoribosylpyrophosphate content and possibly of the purine overproduction described in this syndrome."} {"id": "PMID:171773", "title": "Adenosine 3',5'-monophosphate in reproducing and differentiated trypanosomes.", "content": "Trypanosoma lewisi, a blood protozoan of rats, undergoes differentiation from a rapidly reproducing form to a nonreproducing form in response to the host antibody ablastin. Intracellular concentrations of adenosine 3',5'-monophosphate (cyclic AMP), which has been implicated in controlling reproduction in cultured mammalian cells, was measured in the two developmental forms of T. lewisi. The concentrations were significantly different, and the results support a hypothesis under which ablastin stimulates an increase in intracellular cyclic AMP.", "contents": "Adenosine 3',5'-monophosphate in reproducing and differentiated trypanosomes. Trypanosoma lewisi, a blood protozoan of rats, undergoes differentiation from a rapidly reproducing form to a nonreproducing form in response to the host antibody ablastin. Intracellular concentrations of adenosine 3',5'-monophosphate (cyclic AMP), which has been implicated in controlling reproduction in cultured mammalian cells, was measured in the two developmental forms of T. lewisi. The concentrations were significantly different, and the results support a hypothesis under which ablastin stimulates an increase in intracellular cyclic AMP."} {"id": "PMID:171774", "title": "Diagnostic value of serum creatine phosphokinase in motor neuron disease.", "content": "In ten cases of amyotrophic lateral sclerosis, creatine phosphokinase was, without exception, elevated. In 12 cases of other diseases of the central or peripheral nervous system, values were elevated only in two cases of peripheral neuropathy.", "contents": "Diagnostic value of serum creatine phosphokinase in motor neuron disease. In ten cases of amyotrophic lateral sclerosis, creatine phosphokinase was, without exception, elevated. In 12 cases of other diseases of the central or peripheral nervous system, values were elevated only in two cases of peripheral neuropathy."} {"id": "PMID:171775", "title": "Newer treatment in dermatology.", "content": "The future of a drug depends upon what it can do in the hands of the practitioner. Medicine is practiced on the basis of probabilities, and treatment must be selected which has the best chance of helping the patient, with the least amount of harm. There are many new drugs available for dermatologic therapy in other developed countries which are not available in this country, due to peculiarities of federal drug regulations.", "contents": "Newer treatment in dermatology. The future of a drug depends upon what it can do in the hands of the practitioner. Medicine is practiced on the basis of probabilities, and treatment must be selected which has the best chance of helping the patient, with the least amount of harm. There are many new drugs available for dermatologic therapy in other developed countries which are not available in this country, due to peculiarities of federal drug regulations."} {"id": "PMID:171776", "title": "Autoimmune thrombocytopenia and peripheral neuropathy heralding Hodgkin's disease.", "content": "A patient with an autoimmune thrombocytopenic syndrome was treated unsuccessfully with splenectomy. Treatment with corticosteroids and 6-mercaptopurine was partially successful, but the patient developed peripheral neuropathy and over signs of Hodgkin's disease. The latter reponded completely to radiation therapy, but the thrombocytopenia was not reversed until combination chemotherapy was given. The association of thrombocytopenia with Hodgkin's disease is reviewed.", "contents": "Autoimmune thrombocytopenia and peripheral neuropathy heralding Hodgkin's disease. A patient with an autoimmune thrombocytopenic syndrome was treated unsuccessfully with splenectomy. Treatment with corticosteroids and 6-mercaptopurine was partially successful, but the patient developed peripheral neuropathy and over signs of Hodgkin's disease. The latter reponded completely to radiation therapy, but the thrombocytopenia was not reversed until combination chemotherapy was given. The association of thrombocytopenia with Hodgkin's disease is reviewed."} {"id": "PMID:171777", "title": "Isolated partial deficiency of adrenocorticotrophic hormone.", "content": "A patient with tuberculous empyema who presented with severe hyponatraemia, is described. In the course of investigation, he was discovered to be suffering from isolated adrenocorticotrophic hormone deficiency.", "contents": "Isolated partial deficiency of adrenocorticotrophic hormone. A patient with tuberculous empyema who presented with severe hyponatraemia, is described. In the course of investigation, he was discovered to be suffering from isolated adrenocorticotrophic hormone deficiency."} {"id": "PMID:171778", "title": "D-Thyroxine in hyperbetalipoproteinaemia.", "content": "D-Thyroxine was administered intermittently to 11 patients with hyperlipoproteinaemia (Fredrickson type lla). To avoid possible untoward cardiac stimulation, practolol was prescribed with it. Cholesterol levels were measured regularly over a period of 4 years. A temporary drop of about 15% in the mean cholesterol level was obtained. It is, however, concluded that the over-all response is unimpressive.", "contents": "D-Thyroxine in hyperbetalipoproteinaemia. D-Thyroxine was administered intermittently to 11 patients with hyperlipoproteinaemia (Fredrickson type lla). To avoid possible untoward cardiac stimulation, practolol was prescribed with it. Cholesterol levels were measured regularly over a period of 4 years. A temporary drop of about 15% in the mean cholesterol level was obtained. It is, however, concluded that the over-all response is unimpressive."} {"id": "PMID:171779", "title": "Ultrastructural localisation of calcium in peripheral nerves of the rat.", "content": "An ultrastructural method which is specific for calcium was applied in a study of calcium distribution in the axoplasm of myelinated nerve fibres of rat sciatic nerves. Electron-dense deposits of calcium oxalate were seen in smooth-membraned vesicles within the axoplasm, and between the two external membranes of axoplasmic mitochondria. The significance of calcium localisation at these sites is discussed, with special reference to the role of calcium in fast axoplasmic transport.", "contents": "Ultrastructural localisation of calcium in peripheral nerves of the rat. An ultrastructural method which is specific for calcium was applied in a study of calcium distribution in the axoplasm of myelinated nerve fibres of rat sciatic nerves. Electron-dense deposits of calcium oxalate were seen in smooth-membraned vesicles within the axoplasm, and between the two external membranes of axoplasmic mitochondria. The significance of calcium localisation at these sites is discussed, with special reference to the role of calcium in fast axoplasmic transport."} {"id": "PMID:171780", "title": "Tinidazole for the treatment of amoebic liver abscess.", "content": "Ten patients suffering from amoebic liver abscess were treated with tinidazole (Fasigyn) 800 mg t.d.s. for 5 days. Nine were cured, and 1 patient required further treatment with other drugs. Following this, a double-blind trial was carried out to compare a group of patients treated with tinidazole with a similar group treated with metronidazole. Each series consisted of 14 patients. In the tinidazole series 13 patients were cured and for 1 patient the result of treatment was dubious. All patients in the metronidazole series were cured, but 1 patient admitted to the trial had previously not been cured by metronidazole. It appears that tinidazole and metronidazole are equally efficaceous in the treatment of amoebic liver abscess.", "contents": "Tinidazole for the treatment of amoebic liver abscess. Ten patients suffering from amoebic liver abscess were treated with tinidazole (Fasigyn) 800 mg t.d.s. for 5 days. Nine were cured, and 1 patient required further treatment with other drugs. Following this, a double-blind trial was carried out to compare a group of patients treated with tinidazole with a similar group treated with metronidazole. Each series consisted of 14 patients. In the tinidazole series 13 patients were cured and for 1 patient the result of treatment was dubious. All patients in the metronidazole series were cured, but 1 patient admitted to the trial had previously not been cured by metronidazole. It appears that tinidazole and metronidazole are equally efficaceous in the treatment of amoebic liver abscess."} {"id": "PMID:171781", "title": "Alpha1-antitrypsin deficiency--an association with hepatic malignancy.", "content": "A 70-year-old man with homozygous alpha1-antitrypsin deficiency (AATD) (Pi-ZZ phenotype) at tutopsy was found to have a hepatocellular carcinoma and hepatic fibrosis, pulmonary emphysema, and cor pulmonale. Characteristic cytoplasmic inclusion bodies, with identical histochemical and ultrastructural features, were detected in both normal and malignant liver cells. It is suggested that AATD may precede malignancy, since this is the eleventh case report of this association.", "contents": "Alpha1-antitrypsin deficiency--an association with hepatic malignancy. A 70-year-old man with homozygous alpha1-antitrypsin deficiency (AATD) (Pi-ZZ phenotype) at tutopsy was found to have a hepatocellular carcinoma and hepatic fibrosis, pulmonary emphysema, and cor pulmonale. Characteristic cytoplasmic inclusion bodies, with identical histochemical and ultrastructural features, were detected in both normal and malignant liver cells. It is suggested that AATD may precede malignancy, since this is the eleventh case report of this association."} {"id": "PMID:171783", "title": "Electrical stimulation of the brain. IV. Ultrastructural studies.", "content": "The ultrastructural response of tissues of the cat's central nervous system to chronic electrical stimulation with various parameters has been evaluated at four and a half days post stimulation. Cellular alterations included widespread cytoplasmic vacuolations, architectural derangement and disruption of plasmalemma and other membranes. Lipid inclusions and dense crystalline bodies were prominent in astrocyte-like phagocytic cells in the more severe lesions. Despite endothelial damage in brain parenchymal capillaries, significant extravasation of horseradish peroxidase was not observed. The ultrastructural damage observed following electrical stimulation varied from mild to severe. Although none of the parameters tested was found to be \"safe\" for clinical applications, it should be emphasized that the stimulations delivered in the present study were essentially continuous.", "contents": "Electrical stimulation of the brain. IV. Ultrastructural studies. The ultrastructural response of tissues of the cat's central nervous system to chronic electrical stimulation with various parameters has been evaluated at four and a half days post stimulation. Cellular alterations included widespread cytoplasmic vacuolations, architectural derangement and disruption of plasmalemma and other membranes. Lipid inclusions and dense crystalline bodies were prominent in astrocyte-like phagocytic cells in the more severe lesions. Despite endothelial damage in brain parenchymal capillaries, significant extravasation of horseradish peroxidase was not observed. The ultrastructural damage observed following electrical stimulation varied from mild to severe. Although none of the parameters tested was found to be \"safe\" for clinical applications, it should be emphasized that the stimulations delivered in the present study were essentially continuous."} {"id": "PMID:171784", "title": "Cyclic adenosine monophosphate antagonism of prostaglandin induced vasospasm.", "content": "Prostaglandin F2alpha was applied topically to the transclivally exposed basilar artery of the cat. The resultant vasoconstriction and its reversal by dibutyryl cyclic adenosine monophosphate was recorded photographically and measured, and the results analyzed statistically. Arterial BP, pCO2' pO2 and pH were determined to insure that the vascular responses were not due to any general physiological disturbance. The results indicated that Prostaglandin F2alpha is a powerful vasoconstrictive substance and that its effects are readily reversible by dibutyryl cyclic adenosine monophosphate.", "contents": "Cyclic adenosine monophosphate antagonism of prostaglandin induced vasospasm. Prostaglandin F2alpha was applied topically to the transclivally exposed basilar artery of the cat. The resultant vasoconstriction and its reversal by dibutyryl cyclic adenosine monophosphate was recorded photographically and measured, and the results analyzed statistically. Arterial BP, pCO2' pO2 and pH were determined to insure that the vascular responses were not due to any general physiological disturbance. The results indicated that Prostaglandin F2alpha is a powerful vasoconstrictive substance and that its effects are readily reversible by dibutyryl cyclic adenosine monophosphate."} {"id": "PMID:171785", "title": "Identification and successful treatment of congenital microfistulas with the aid of directional Doppler.", "content": "Hitherto unidentifiable and therefore untreatable congenital microfistulas were detected with the aid of continuous-wave directional Doppler and a fine-beam pencil probe. The microfistulas formed part of the Klippel-Trenaunay (K-T) syndrome. The management of one case is reported in detail and in three others salient features are touched upon. Careful clinical and radiological examination failed to demonstrate any arteriovenous microfistulas. When Doppler ultrasound scanning was carried out, two discrete fistulas were discovered. Their extent and direction were mapped out accurately. Incisions were made directly over the markings displaying a pulsating capillary tuft of vessels. Further dissection exposed a feeding arteriole which was less than 1 mm. in diameter. Excision of the vascular malformations resulted in the cure of the patient. In another patient with the K-T syndrome in whom a cutaneous hemangioma involved the whole lower limb, in spite of a thorough and systematic search with a Doppler, no microfistulas could be demonstrated. It is suggested that all patients suffering from the K-T syndrome should be examined by Doppler ultrasound in the hope that microfistulas which elude radiodiagnostic techniques might be detected and treated surgically.", "contents": "Identification and successful treatment of congenital microfistulas with the aid of directional Doppler. Hitherto unidentifiable and therefore untreatable congenital microfistulas were detected with the aid of continuous-wave directional Doppler and a fine-beam pencil probe. The microfistulas formed part of the Klippel-Trenaunay (K-T) syndrome. The management of one case is reported in detail and in three others salient features are touched upon. Careful clinical and radiological examination failed to demonstrate any arteriovenous microfistulas. When Doppler ultrasound scanning was carried out, two discrete fistulas were discovered. Their extent and direction were mapped out accurately. Incisions were made directly over the markings displaying a pulsating capillary tuft of vessels. Further dissection exposed a feeding arteriole which was less than 1 mm. in diameter. Excision of the vascular malformations resulted in the cure of the patient. In another patient with the K-T syndrome in whom a cutaneous hemangioma involved the whole lower limb, in spite of a thorough and systematic search with a Doppler, no microfistulas could be demonstrated. It is suggested that all patients suffering from the K-T syndrome should be examined by Doppler ultrasound in the hope that microfistulas which elude radiodiagnostic techniques might be detected and treated surgically."} {"id": "PMID:171791", "title": "Growth of permanent lymphoid cell cultures from human source: tenth anniversary.", "content": "The authors developed 52 permanent lymphoid cell cultures from various human sources, mainly from neoplastic lymphoproliferative disease. These cultures are reviewed against the background of similar cultures obtained in several other laboratories. The peculiar features of these cultures are: 1) the phenomenon of lymphoblastoid transformation; 2) the production of both globulins and mediators of delayed hypersensitivity; 3) the presence of herpes type virus as related to etiology or autoimmunity; and 4) cytotoxicity and other assays for the demonstration of tumor-specific antigens.", "contents": "Growth of permanent lymphoid cell cultures from human source: tenth anniversary. The authors developed 52 permanent lymphoid cell cultures from various human sources, mainly from neoplastic lymphoproliferative disease. These cultures are reviewed against the background of similar cultures obtained in several other laboratories. The peculiar features of these cultures are: 1) the phenomenon of lymphoblastoid transformation; 2) the production of both globulins and mediators of delayed hypersensitivity; 3) the presence of herpes type virus as related to etiology or autoimmunity; and 4) cytotoxicity and other assays for the demonstration of tumor-specific antigens."} {"id": "PMID:171792", "title": "The role of heavy metals in human health.", "content": "The article reviews the role of heavy metals in human health, including those which are biochemically essential as well as those which have no known role in the normal functioning of the organism but which are toxic. The metals discussed are: cobalt, copper, manganese, cadmium, lead, and mercury. Several are also of concern from the point of view of environmental contamination. The article describes the biochemical role for those metals that are essential, mechanisms of intoxication, intake routes and quantities, and environmental significance.", "contents": "The role of heavy metals in human health. The article reviews the role of heavy metals in human health, including those which are biochemically essential as well as those which have no known role in the normal functioning of the organism but which are toxic. The metals discussed are: cobalt, copper, manganese, cadmium, lead, and mercury. Several are also of concern from the point of view of environmental contamination. The article describes the biochemical role for those metals that are essential, mechanisms of intoxication, intake routes and quantities, and environmental significance."} {"id": "PMID:171793", "title": "Hypertension from compression and/or enucleation of the adrenal glands in the rat.", "content": "Previos studies have shown that compression of the adrenal glands is as effective as adrenal enucleation in causing hypertension in rats. Unilateral adrenal enucleation is ineffective, however, if a normal contralateral adrenal gland is present. The studies reported herein demonstrate that unilateral compression also fails to cause hypertension in the presence of a normal contralateral gland. When present singly, either enucleate or compressed adrenals cause hypertension; when either is present with a normal contralateral gland, the blood pressure is unaffected. When compressed or enucleate glands constitute the pair, in any combination, hypertension ensues. However, whereas an enucleate gland remains extremely atrophic in the presence of a normal gland, compressed glands attain a much larger size under this circumstance. Furthermore, a compressed gland is less inhibitory to the regeneration of a contralateral enucleate gland than is a normal adrenal. Whereas enucleate glands, whether bilateral or unilateral, are always smaller than normal glands, compressed adrenals may be enlarged. The hypertensogenic function of compressed adrenals is, like that of enucleate glands, suppressed by the presence of a normal gland. The growth response of compressed or enucleate glands, whether bilateral or single, appears to depend upon the degree of injury inflicted upon them. There is a considerable discrepancy in the size of individual members of a pair when one or both have been injured, that members of a normal pair do not exhibit.", "contents": "Hypertension from compression and/or enucleation of the adrenal glands in the rat. Previos studies have shown that compression of the adrenal glands is as effective as adrenal enucleation in causing hypertension in rats. Unilateral adrenal enucleation is ineffective, however, if a normal contralateral adrenal gland is present. The studies reported herein demonstrate that unilateral compression also fails to cause hypertension in the presence of a normal contralateral gland. When present singly, either enucleate or compressed adrenals cause hypertension; when either is present with a normal contralateral gland, the blood pressure is unaffected. When compressed or enucleate glands constitute the pair, in any combination, hypertension ensues. However, whereas an enucleate gland remains extremely atrophic in the presence of a normal gland, compressed glands attain a much larger size under this circumstance. Furthermore, a compressed gland is less inhibitory to the regeneration of a contralateral enucleate gland than is a normal adrenal. Whereas enucleate glands, whether bilateral or unilateral, are always smaller than normal glands, compressed adrenals may be enlarged. The hypertensogenic function of compressed adrenals is, like that of enucleate glands, suppressed by the presence of a normal gland. The growth response of compressed or enucleate glands, whether bilateral or single, appears to depend upon the degree of injury inflicted upon them. There is a considerable discrepancy in the size of individual members of a pair when one or both have been injured, that members of a normal pair do not exhibit."} {"id": "PMID:171794", "title": "Disseminated intravascular coagulation: experience in a major cancer center.", "content": "Review of the coagulation laboratory records and medical records at Memorial Sloan-Kettering Cancer Center over a three year period (1971--1974) revealed 89 patients with disseminated intravascular coagulation (DIC). The diagnosis of DIC was made if laboratory studies showed evidence of quantitative and qualitative changes in fibrinogen and significant thrombocytopenia. The patients included 19 with leukemia (17 acute), 3 with multiple myeloma, 15 with lymphoma, 46 with metastatic solid tumors, (10 lung, 9 breast, 8 gastrointestinal, 12 genitourinary, 7 miscellaneous) 4 with vascular tumors, and 3 without tumor. Other conditions which might have precipitated or initiated DIC such as gram-negative sepsis, liver impairment, or mucin secreting tumors were present in the majority of patients. Bleeding occurred in 75% of the patients and was fatal in 36%. Thromboembolism occurred in 22.5%. Thirteen percent were asymptomatic. Serum lactic dehydrogenase was elevated in over 75% of the patients at the time of, or subsequent to the occurrence of DIC. Treatment with heparin was helpful in only three of twenty patients. Eighty percent of the patients died within one to over 30 days of the onset of DIC. Post mortem evidence of DIC was present in 18 of 43 autopsies. Results of this study indicate that DIC is a frequent complication of a wide variety of tumors and that its occurrence causes morbidity and mortality in a significant number of patients. Treatment with heparin is of little help unless remission is induced and the precipitating factor(s) are reversed.", "contents": "Disseminated intravascular coagulation: experience in a major cancer center. Review of the coagulation laboratory records and medical records at Memorial Sloan-Kettering Cancer Center over a three year period (1971--1974) revealed 89 patients with disseminated intravascular coagulation (DIC). The diagnosis of DIC was made if laboratory studies showed evidence of quantitative and qualitative changes in fibrinogen and significant thrombocytopenia. The patients included 19 with leukemia (17 acute), 3 with multiple myeloma, 15 with lymphoma, 46 with metastatic solid tumors, (10 lung, 9 breast, 8 gastrointestinal, 12 genitourinary, 7 miscellaneous) 4 with vascular tumors, and 3 without tumor. Other conditions which might have precipitated or initiated DIC such as gram-negative sepsis, liver impairment, or mucin secreting tumors were present in the majority of patients. Bleeding occurred in 75% of the patients and was fatal in 36%. Thromboembolism occurred in 22.5%. Thirteen percent were asymptomatic. Serum lactic dehydrogenase was elevated in over 75% of the patients at the time of, or subsequent to the occurrence of DIC. Treatment with heparin was helpful in only three of twenty patients. Eighty percent of the patients died within one to over 30 days of the onset of DIC. Post mortem evidence of DIC was present in 18 of 43 autopsies. Results of this study indicate that DIC is a frequent complication of a wide variety of tumors and that its occurrence causes morbidity and mortality in a significant number of patients. Treatment with heparin is of little help unless remission is induced and the precipitating factor(s) are reversed."} {"id": "PMID:171798", "title": "Dependence of platelet adenyl cyclase system on oxidative phosphorylation.", "content": "The radioactive adenosine 3',5'-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.", "contents": "Dependence of platelet adenyl cyclase system on oxidative phosphorylation. The radioactive adenosine 3',5'-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation."} {"id": "PMID:171799", "title": "Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats.", "content": "Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal.", "contents": "Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats. Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal."} {"id": "PMID:171800", "title": "Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus).", "content": "In order to characterize pancreatic beta cell function in Geneva bred spiny mice (acomys cahirinus), the dynamics of immunoreactive insulin release were examined during perifusion of pancreatic islets isolated from normoglycemic acomys. The initial insulin response of acomys was slow: no clear-cut early (1 to 10 min) peak of insulin release was observed when glucose in the perifusion medium was abruptly raised from 2.8 mM to concentrations as high as 56 mM. This was true for islets of either young, or older more obese acomys. However, after 20 to 30 min of perifusion at the high glucose concentrations, the rate of insulin release from acomysislets became similar to that from islets of rats or mice. By contrast, glucose-induced insulin release responses observed with islets of Wistar-derived rats, Swiss albino mice, and inbred C57BL/6J lean or obese (ob/ob) mice, were clearly biphasic. Tolbutamide 1.5 mM, arginine 16 mM, and theophylline 10 mM were ineffective in stimulating insulin release from acomys islets in the presence of a substimulatory glucose concentration (2.8 mM), whereas these agents were effective in rat islets at the same substimulatory concentration of glucose. On the other hand, when these agents, as well as cyclic AMP 10 mM or cytochalasin B 10 mug/ml were applied in the presence of a stimulating concentration of glucose (16.8 mM), the glucose-stimulated insulin release from acomys islets was increased to the same or to a greater extent than from rat islets. It is suggested that the failure of all the agents tested to stimulate an early rapid phase of insulin release from acomys islets may be secondary to the observed initial insensitivity to glucose, which insensitivity may in turn reflect a selective impairment in the recognition of glucose as an insulinogenic signal in this species.", "contents": "Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus). In order to characterize pancreatic beta cell function in Geneva bred spiny mice (acomys cahirinus), the dynamics of immunoreactive insulin release were examined during perifusion of pancreatic islets isolated from normoglycemic acomys. The initial insulin response of acomys was slow: no clear-cut early (1 to 10 min) peak of insulin release was observed when glucose in the perifusion medium was abruptly raised from 2.8 mM to concentrations as high as 56 mM. This was true for islets of either young, or older more obese acomys. However, after 20 to 30 min of perifusion at the high glucose concentrations, the rate of insulin release from acomysislets became similar to that from islets of rats or mice. By contrast, glucose-induced insulin release responses observed with islets of Wistar-derived rats, Swiss albino mice, and inbred C57BL/6J lean or obese (ob/ob) mice, were clearly biphasic. Tolbutamide 1.5 mM, arginine 16 mM, and theophylline 10 mM were ineffective in stimulating insulin release from acomys islets in the presence of a substimulatory glucose concentration (2.8 mM), whereas these agents were effective in rat islets at the same substimulatory concentration of glucose. On the other hand, when these agents, as well as cyclic AMP 10 mM or cytochalasin B 10 mug/ml were applied in the presence of a stimulating concentration of glucose (16.8 mM), the glucose-stimulated insulin release from acomys islets was increased to the same or to a greater extent than from rat islets. It is suggested that the failure of all the agents tested to stimulate an early rapid phase of insulin release from acomys islets may be secondary to the observed initial insensitivity to glucose, which insensitivity may in turn reflect a selective impairment in the recognition of glucose as an insulinogenic signal in this species."} {"id": "PMID:171801", "title": "Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls.", "content": "Pretreatment of male rats with Aroclor 1254 at a dose of 25 mg/kg i.p. for 6 days resulted in potentiation of the hepatotoxicity of inhaled carbon tetrachloride (CCl4) as evidenced by a decrease in liver glucose-6-phosphatase and elevations of serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), isocitrate dehydrogenase, and sorbitol dehydrogenase. Aroclor 1254 alone did not demonstrate hepatotoxicity. Aroclor 1254 administration resulted in large increases in cytochrome c reductase, cytochrome P-450 (448) AND P-Nitroanisole demethylation. Subsequent exposure to CCl4 vapor resulted in over 70% decreases in the latter two parameters. The potentiation was dose-dependent with a dose of 5 mg/kg or higher being effective. Aroclor 1260 administration gave results similar to those of Aroclor 1254, but Aroclor 1221 enhanced CCl4 toxicity to a lesser extent.", "contents": "Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls. Pretreatment of male rats with Aroclor 1254 at a dose of 25 mg/kg i.p. for 6 days resulted in potentiation of the hepatotoxicity of inhaled carbon tetrachloride (CCl4) as evidenced by a decrease in liver glucose-6-phosphatase and elevations of serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), isocitrate dehydrogenase, and sorbitol dehydrogenase. Aroclor 1254 alone did not demonstrate hepatotoxicity. Aroclor 1254 administration resulted in large increases in cytochrome c reductase, cytochrome P-450 (448) AND P-Nitroanisole demethylation. Subsequent exposure to CCl4 vapor resulted in over 70% decreases in the latter two parameters. The potentiation was dose-dependent with a dose of 5 mg/kg or higher being effective. Aroclor 1260 administration gave results similar to those of Aroclor 1254, but Aroclor 1221 enhanced CCl4 toxicity to a lesser extent."} {"id": "PMID:171802", "title": "The effects of a polychlorinated biphenyl mixture (Aroclor 1254) on liver gluconeogenic enzymes of normal and alloxan-diabetic rats.", "content": "Normal and alloxan-diabetic rats were fed ground Purina Laboratory Chow with or without 500 ppm of Aroclor 1254 (AR) ad lib for 2 weeks. In both normal and diabetic rats, AR administration decreased food consumption, weight gain and blood glucose concentration, and increased liver weight, liver:body weight ratio, total liver lipid, liver protein and malic enzyme (ME) activity. In the normal rat, AR increased the concentrations of acetoacetate and beta-hydroxybutyrate in blood, but in the diabetic rat the concentrations were markedly reduced. AR administration decreased the activity of phosphoenolpyruvate carboxykinase (PEPck) in normal liver and the activities of pyruvate carboxylase (PC), PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver.", "contents": "The effects of a polychlorinated biphenyl mixture (Aroclor 1254) on liver gluconeogenic enzymes of normal and alloxan-diabetic rats. Normal and alloxan-diabetic rats were fed ground Purina Laboratory Chow with or without 500 ppm of Aroclor 1254 (AR) ad lib for 2 weeks. In both normal and diabetic rats, AR administration decreased food consumption, weight gain and blood glucose concentration, and increased liver weight, liver:body weight ratio, total liver lipid, liver protein and malic enzyme (ME) activity. In the normal rat, AR increased the concentrations of acetoacetate and beta-hydroxybutyrate in blood, but in the diabetic rat the concentrations were markedly reduced. AR administration decreased the activity of phosphoenolpyruvate carboxykinase (PEPck) in normal liver and the activities of pyruvate carboxylase (PC), PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver."} {"id": "PMID:171803", "title": "Histopathologic changes induced in rats by localized x-irradiation of an exteriorized segment of the small intestine.", "content": "The sequence of histopathological changes was described after X-irradiation of the exteriorized segment (3 cm) of the rat ileum with a single dose of 2200 R. A one-year follow-up was provided in rats whose exteriorized intestinal segments were irradiated. Comparisons were made between one group of animals in which the superior mesentric artery and vein were clamped during irradiation and a second group in which these vessels were not clamped. A third group of sham-irradiated controls was used for comparisons. There was a delay in the onset and progression of the radiation damage to the mucosa of the hypoxic animals in the acute post-irradiation phase. In addition, prolongation of survival in the rats with the superior mesenteric vessels clamped was observed. Mucosal regeneration was noted, occurring at 52 days post-exposure. No adenocarcinomas were found up to 354 days after irradiation. An angiofibroma and a highly differentiated osteoid lesion were described.", "contents": "Histopathologic changes induced in rats by localized x-irradiation of an exteriorized segment of the small intestine. The sequence of histopathological changes was described after X-irradiation of the exteriorized segment (3 cm) of the rat ileum with a single dose of 2200 R. A one-year follow-up was provided in rats whose exteriorized intestinal segments were irradiated. Comparisons were made between one group of animals in which the superior mesentric artery and vein were clamped during irradiation and a second group in which these vessels were not clamped. A third group of sham-irradiated controls was used for comparisons. There was a delay in the onset and progression of the radiation damage to the mucosa of the hypoxic animals in the acute post-irradiation phase. In addition, prolongation of survival in the rats with the superior mesenteric vessels clamped was observed. Mucosal regeneration was noted, occurring at 52 days post-exposure. No adenocarcinomas were found up to 354 days after irradiation. An angiofibroma and a highly differentiated osteoid lesion were described."} {"id": "PMID:171804", "title": "Radiation effects on alkaline phosphatase and glucose-6-phosphatase in anatomically different regions of mouse intestine.", "content": "The effect of gamma irradiation on alkaline phosphatase and glucose-6-phosphate has been studied in three anatomically different regions of the small intestine at a surface dose of 400 R. Both the enzymatic activities were shown to be enhanced in duodenum, jejunum and ileum 24 hours after irradiation. The activity of alkaline phosphatase on day 3 tendeed to be low as compared to day 1 post irradiation, but glucose-6-phosphatase continued to rise even after day 3. Maximum rise of glucose-6-phosphatase was observed in the jejunum. On day 9, alkaline phosphatase was diminished below the controls in the whole of intestine, but appeared to be normal on day 10. Glucose-6-phosphatase in duodenum and jejunum on the other hand was comparable to that of control mice; but in ileum, the activity of this enzyme was below the normal values. Physiological significances of these enzymes in intestine has been discussed.", "contents": "Radiation effects on alkaline phosphatase and glucose-6-phosphatase in anatomically different regions of mouse intestine. The effect of gamma irradiation on alkaline phosphatase and glucose-6-phosphate has been studied in three anatomically different regions of the small intestine at a surface dose of 400 R. Both the enzymatic activities were shown to be enhanced in duodenum, jejunum and ileum 24 hours after irradiation. The activity of alkaline phosphatase on day 3 tendeed to be low as compared to day 1 post irradiation, but glucose-6-phosphatase continued to rise even after day 3. Maximum rise of glucose-6-phosphatase was observed in the jejunum. On day 9, alkaline phosphatase was diminished below the controls in the whole of intestine, but appeared to be normal on day 10. Glucose-6-phosphatase in duodenum and jejunum on the other hand was comparable to that of control mice; but in ileum, the activity of this enzyme was below the normal values. Physiological significances of these enzymes in intestine has been discussed."} {"id": "PMID:171805", "title": "Ammonium sulfate precipitation as a tool for the study of androgen receptor proteins in rat prostate and mouse kidney.", "content": "Ammonium sulfate precipitation has been used for the separation of bound and free steroids in rat prostate and mouse kidney cytosol equilibrated with tritiated androgens. A high affinity, low capacity binding protein has been identified in the 35% saturation precipitate. Biochemical and physiological data indicate that this protein is identical with the previously described 8-10 S androgen receptor. It has been demonstrated that this receptor protein binds 17 beta - hydroxy-5alpha-androstan-3-one (DHT) and testosterone in both tissues. The apparent dissociation constant (Kd) of the prostatic receptor for DHT and of the renal receptor for testosterone is 1-2 nM. The number of binding sites equals 57 and 23 fmoles/mg protein in prostate and kidney respectively. Dterminations of apparent inhibition constants (Ki) for 26 steroidal and non-steroidal compounds suggest that the binding sites in these tissues is similar or identical.", "contents": "Ammonium sulfate precipitation as a tool for the study of androgen receptor proteins in rat prostate and mouse kidney. Ammonium sulfate precipitation has been used for the separation of bound and free steroids in rat prostate and mouse kidney cytosol equilibrated with tritiated androgens. A high affinity, low capacity binding protein has been identified in the 35% saturation precipitate. Biochemical and physiological data indicate that this protein is identical with the previously described 8-10 S androgen receptor. It has been demonstrated that this receptor protein binds 17 beta - hydroxy-5alpha-androstan-3-one (DHT) and testosterone in both tissues. The apparent dissociation constant (Kd) of the prostatic receptor for DHT and of the renal receptor for testosterone is 1-2 nM. The number of binding sites equals 57 and 23 fmoles/mg protein in prostate and kidney respectively. Dterminations of apparent inhibition constants (Ki) for 26 steroidal and non-steroidal compounds suggest that the binding sites in these tissues is similar or identical."} {"id": "PMID:171806", "title": "Methyltrienolone, a specific ligand for cellular androgen receptors.", "content": "Methyltrienolone (R 1881), 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one, a very active androgen, binds specifically to rat prostate cytosol with a higher affinity than androstanolone. Unlike the physiological hormone, however, it is not bound by human sex steroid plasma binding protein, SBP. This specific ligand is thus a useful tool for the detection of elusive androgen receptors and for their study, for instance, in human tumors where interference from plasma contamination has to be circumvented.", "contents": "Methyltrienolone, a specific ligand for cellular androgen receptors. Methyltrienolone (R 1881), 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one, a very active androgen, binds specifically to rat prostate cytosol with a higher affinity than androstanolone. Unlike the physiological hormone, however, it is not bound by human sex steroid plasma binding protein, SBP. This specific ligand is thus a useful tool for the detection of elusive androgen receptors and for their study, for instance, in human tumors where interference from plasma contamination has to be circumvented."} {"id": "PMID:171807", "title": "Immunochemical comparison of estradiol-binding molecules in perinatal rat brain cytosol and serum.", "content": "Estradiol-binding macromolecules in fetoneonatal rat brain cytosol and serum were compared by immunochemical techniques. When treated by a double diffusion procedure, both cytosol and serum formed precipitin lines with rabbit antiserum specific for perinatal rat serum proteins. These lines fused completely, indicating, within the limits of detection of this particular antiserum, the presence of identical antigenic determinants in the brain and serum. Prior removal of immunoprecipitable material from cytosol or serum, after incubation with the specific antiserum, prevented formation of such precipitin lines. The procedure similarly presented specific estradiol-binding to macromolecules. It was therefore concluded that the specifically perinatal, antigenically similar, components in rat brain cytosol and serum (possibly representing alphafetoprotein) are responsible for the estradiol-binding activity in these two tissue compartments. Measurements of heme concentrations indicated that the alphafetoprotein-like material in the cytosol does not reflect blood contamination, but rather a separate population of similar or identical molecules.", "contents": "Immunochemical comparison of estradiol-binding molecules in perinatal rat brain cytosol and serum. Estradiol-binding macromolecules in fetoneonatal rat brain cytosol and serum were compared by immunochemical techniques. When treated by a double diffusion procedure, both cytosol and serum formed precipitin lines with rabbit antiserum specific for perinatal rat serum proteins. These lines fused completely, indicating, within the limits of detection of this particular antiserum, the presence of identical antigenic determinants in the brain and serum. Prior removal of immunoprecipitable material from cytosol or serum, after incubation with the specific antiserum, prevented formation of such precipitin lines. The procedure similarly presented specific estradiol-binding to macromolecules. It was therefore concluded that the specifically perinatal, antigenically similar, components in rat brain cytosol and serum (possibly representing alphafetoprotein) are responsible for the estradiol-binding activity in these two tissue compartments. Measurements of heme concentrations indicated that the alphafetoprotein-like material in the cytosol does not reflect blood contamination, but rather a separate population of similar or identical molecules."} {"id": "PMID:171808", "title": "Gastric cancer in Sudan.", "content": "All gastric tumours received in the University Department of Pathology and the National Laboratory between 1970-1974 were re-examined. Of 35 such tumours, 28 were carcinomas, 6 malignant lymphomas and 1 leiomyosarcoma. Histological grading showed that the majority of the patients reported in the very advanced stages of the disease. Accordingly, the resectability rate was low. The incidence of primary malignant lymphoma of the stomach (16.6%) is much higher than in Western countries but is in accord with reports from countries in the Mediterranean basin.", "contents": "Gastric cancer in Sudan. All gastric tumours received in the University Department of Pathology and the National Laboratory between 1970-1974 were re-examined. Of 35 such tumours, 28 were carcinomas, 6 malignant lymphomas and 1 leiomyosarcoma. Histological grading showed that the majority of the patients reported in the very advanced stages of the disease. Accordingly, the resectability rate was low. The incidence of primary malignant lymphoma of the stomach (16.6%) is much higher than in Western countries but is in accord with reports from countries in the Mediterranean basin."} {"id": "PMID:171809", "title": "Serological study of amebiasis and toxoplasmosis in the Lindu Valley, Central Sulawesi, Indonesia.", "content": "Results of a serology survey in April 1972 for Entamoeba histolytica and Toxoplasma gondii antibodies among 484 inhabitants of the isolated Lake Lindu Valley of Central Sulawesi (Celebes) are presented. Indirect hemagglutination antibody titers for amebiasis were found in over 10% of the population, although only 3.7% demonstrated significant titers of 1:128 or greater. There appeared to be no relationship between antibody titers and the age and sex of individuals tested, and the frequency distribution of antibody titers indicates a low prevalence of invasive amebiasis in the population. Indirect hemagglutination antibody titers for Toxoplasma gondii equal to or greater than 1:32 were found in 27.1% of the total population, and it appeared that the prevalence of titers increased with age in both sexes. More families with cats had Toxoplasma gondii antibody titers than families without cats.", "contents": "Serological study of amebiasis and toxoplasmosis in the Lindu Valley, Central Sulawesi, Indonesia. Results of a serology survey in April 1972 for Entamoeba histolytica and Toxoplasma gondii antibodies among 484 inhabitants of the isolated Lake Lindu Valley of Central Sulawesi (Celebes) are presented. Indirect hemagglutination antibody titers for amebiasis were found in over 10% of the population, although only 3.7% demonstrated significant titers of 1:128 or greater. There appeared to be no relationship between antibody titers and the age and sex of individuals tested, and the frequency distribution of antibody titers indicates a low prevalence of invasive amebiasis in the population. Indirect hemagglutination antibody titers for Toxoplasma gondii equal to or greater than 1:32 were found in 27.1% of the total population, and it appeared that the prevalence of titers increased with age in both sexes. More families with cats had Toxoplasma gondii antibody titers than families without cats."} {"id": "PMID:171810", "title": "[Detection of the range of cytological changes in tumors induced in rats by nitrosoamines by means of passage in the anterior chamber of the eye].", "content": "12 rat liver tumors (high, purely and low differentiated hepatomas and adenocarcinomas), 3 kidney tumors, 1 lymphosarcoma and 1 round cell sarcoma of the uterus were transplanted and passed trough anterior chamber of the allogenic rat eyes. In 8 primary transplants of the liver tumors differentiation traits increased; three of them were morphologically undistinguishable from the normal liver tissue. In some transplants of embryonic liver and kidney displasia was detected. The results obtained give evidence in favor of a very high cytological variability of tumors at the early steps of progression, and indicate that the cultivation in the anterior chamber of the eye may be a proper model for investigation of cytological variability of both malignant and normal tissues.", "contents": "[Detection of the range of cytological changes in tumors induced in rats by nitrosoamines by means of passage in the anterior chamber of the eye]. 12 rat liver tumors (high, purely and low differentiated hepatomas and adenocarcinomas), 3 kidney tumors, 1 lymphosarcoma and 1 round cell sarcoma of the uterus were transplanted and passed trough anterior chamber of the allogenic rat eyes. In 8 primary transplants of the liver tumors differentiation traits increased; three of them were morphologically undistinguishable from the normal liver tissue. In some transplants of embryonic liver and kidney displasia was detected. The results obtained give evidence in favor of a very high cytological variability of tumors at the early steps of progression, and indicate that the cultivation in the anterior chamber of the eye may be a proper model for investigation of cytological variability of both malignant and normal tissues."} {"id": "PMID:171813", "title": "Interaction of ultrasound with neoplastic tissue. Local effect on subcutaneously implanted Furth-Columbia rat Wilms' tumor.", "content": "Ultrasonic irradiation was employed by direct administration to the skin overlying subcutaneously implanted Furth-Columbia rat Wilms' tumors. Treated tumors were flattened and excavated and demonstrated no stigmata of hemorrhage or infection. There was a marked decrease in growth rate of the tumors with an increase in survival time of the host. Histologic assessment with the light microscope exhibited a sharp line of demarcation between the necrosed sonicated portion of tumor and the viable intact nonsonicated area of tumor. A blackened area of skin, which was not histologically similar to a burn, was interposed betwwen the site of application of the ultrasound and the necrosed tumor.", "contents": "Interaction of ultrasound with neoplastic tissue. Local effect on subcutaneously implanted Furth-Columbia rat Wilms' tumor. Ultrasonic irradiation was employed by direct administration to the skin overlying subcutaneously implanted Furth-Columbia rat Wilms' tumors. Treated tumors were flattened and excavated and demonstrated no stigmata of hemorrhage or infection. There was a marked decrease in growth rate of the tumors with an increase in survival time of the host. Histologic assessment with the light microscope exhibited a sharp line of demarcation between the necrosed sonicated portion of tumor and the viable intact nonsonicated area of tumor. A blackened area of skin, which was not histologically similar to a burn, was interposed betwwen the site of application of the ultrasound and the necrosed tumor."} {"id": "PMID:171819", "title": "[Surgical tactics in malignant forms of ulcerogenic tumors of the pancreas].", "content": "According to the authors' findings malignant forms of ulcerogenic tumors of the pancreas in the Zollinger-Ellison syndrome clinically show a relatively favourable course in oncological aspect. As a rule, patients die from complications of peptic ulcer before a progressive tumor growth or its metastases result in mortality. Therefore, in cases when the routine radical operators prove to be unfeasible, it is recommended to perform surgery for the purpose of liquidating ulcer and conditions for its recurrence.", "contents": "[Surgical tactics in malignant forms of ulcerogenic tumors of the pancreas]. According to the authors' findings malignant forms of ulcerogenic tumors of the pancreas in the Zollinger-Ellison syndrome clinically show a relatively favourable course in oncological aspect. As a rule, patients die from complications of peptic ulcer before a progressive tumor growth or its metastases result in mortality. Therefore, in cases when the routine radical operators prove to be unfeasible, it is recommended to perform surgery for the purpose of liquidating ulcer and conditions for its recurrence."} {"id": "PMID:171821", "title": "[Testing of the protective effect of cell-free lyophilized vaccine against Marek's disease in field trials].", "content": "The protective effect of a lyophilized vaccine against Marek's disease (\"Keramvac\"--Pfizer), prepared from a cell-free turkey's herpesvirus (strain FC 126), was compared in field trials with losses in the group of non-vaccinated chickens. Under the indicated conditions, the vaccine had only a 50.86% effectiveness. The possible causes of the reduced vaccination effect are discussed with regard to the pathomorphological and virological findings suggesting, among others, an increased incidence of the symptoms of the classical form of Marek's disease in the population investigated.", "contents": "[Testing of the protective effect of cell-free lyophilized vaccine against Marek's disease in field trials]. The protective effect of a lyophilized vaccine against Marek's disease (\"Keramvac\"--Pfizer), prepared from a cell-free turkey's herpesvirus (strain FC 126), was compared in field trials with losses in the group of non-vaccinated chickens. Under the indicated conditions, the vaccine had only a 50.86% effectiveness. The possible causes of the reduced vaccination effect are discussed with regard to the pathomorphological and virological findings suggesting, among others, an increased incidence of the symptoms of the classical form of Marek's disease in the population investigated."} {"id": "PMID:171822", "title": "Hepatic drug metabolism and adverse hepatic drug reactions.", "content": "Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin.", "contents": "Hepatic drug metabolism and adverse hepatic drug reactions. Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin."} {"id": "PMID:171824", "title": "[Role of the virus of Aujeszky's disease in respiratory diseases of swine].", "content": "Studies carried out on pig-breeding farms have established the presence of Aujeszky's disease virus in cases of bronchopneumonia in pigs. On seven out of eight farms with bronchopneumonia the virus wad demonstrated both virologically and serologically, and nearly 50 per cent of the examined diseased pigs on these and other farms had antibodies. The individual serologic studies of pigs having antibodies revealed that the antibodies appeared in the second month of the animals' fattening. This corresponded to the manifestation of the initial symptoms of bronchopneumonia in the respective group.", "contents": "[Role of the virus of Aujeszky's disease in respiratory diseases of swine]. Studies carried out on pig-breeding farms have established the presence of Aujeszky's disease virus in cases of bronchopneumonia in pigs. On seven out of eight farms with bronchopneumonia the virus wad demonstrated both virologically and serologically, and nearly 50 per cent of the examined diseased pigs on these and other farms had antibodies. The individual serologic studies of pigs having antibodies revealed that the antibodies appeared in the second month of the animals' fattening. This corresponded to the manifestation of the initial symptoms of bronchopneumonia in the respective group."} {"id": "PMID:171825", "title": "[Isolation and identification of a virus causing abortions and stillbirths in swine (Preliminary report)].", "content": "A virus of the RNA type, having no lipid envelope, acid-fast and stable to heat, was isolated from an aborted fetus and from the kidney of a piglet of a lower viability at birth. It was readily cultured, multiplying quickly in primary cell cultures of pig kidney and in the SPEV cell line, producing a characteristic cytopathic effect. It gave no hemagglutination with human, chicken, and swine erythrocytes. Serologically, it was identified as a swine enterovirus of serotype I, identical with the viruses described as the etiologic agents of SMEDI.", "contents": "[Isolation and identification of a virus causing abortions and stillbirths in swine (Preliminary report)]. A virus of the RNA type, having no lipid envelope, acid-fast and stable to heat, was isolated from an aborted fetus and from the kidney of a piglet of a lower viability at birth. It was readily cultured, multiplying quickly in primary cell cultures of pig kidney and in the SPEV cell line, producing a characteristic cytopathic effect. It gave no hemagglutination with human, chicken, and swine erythrocytes. Serologically, it was identified as a swine enterovirus of serotype I, identical with the viruses described as the etiologic agents of SMEDI."} {"id": "PMID:171826", "title": "Ultrastructural and immunohistochemical study of the human kidney in Argentine haemorrhagic fever.", "content": "In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells.", "contents": "Ultrastructural and immunohistochemical study of the human kidney in Argentine haemorrhagic fever. In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells."} {"id": "PMID:171827", "title": "Ultrastructure of pulmonary granulomatosis induced in rats by intravenous complete Freund's adjuvant.", "content": "Following the intravenous injection of complete Freund's adjuvant, changes in the rat lung were studied with the electron microscope. Interstitial granulomas were produced and whereas on light microscopy these appeared to consist mainly of epitheloid cells, electron microscopy showed that the granulomas were largely made up of macrophages. Epithelioid cells were in fact few in number, atypical in appearance and limited to the periphery of some granulomas. Fenestrated capillaries were also found at the edge of the granulomas. The alveolar macrophages were increased in number and size but marked cytoplasmic vacuolation and a paucity of lysosomes are consistent with our previous suggestion that the phagocytic and migratory properties of these cells are weakened or inhibited. Alterations were found in both types of alveolar epithelial cell with the appearance of intermediate cell forms.", "contents": "Ultrastructure of pulmonary granulomatosis induced in rats by intravenous complete Freund's adjuvant. Following the intravenous injection of complete Freund's adjuvant, changes in the rat lung were studied with the electron microscope. Interstitial granulomas were produced and whereas on light microscopy these appeared to consist mainly of epitheloid cells, electron microscopy showed that the granulomas were largely made up of macrophages. Epithelioid cells were in fact few in number, atypical in appearance and limited to the periphery of some granulomas. Fenestrated capillaries were also found at the edge of the granulomas. The alveolar macrophages were increased in number and size but marked cytoplasmic vacuolation and a paucity of lysosomes are consistent with our previous suggestion that the phagocytic and migratory properties of these cells are weakened or inhibited. Alterations were found in both types of alveolar epithelial cell with the appearance of intermediate cell forms."} {"id": "PMID:171828", "title": "A light and electron microscopic study of endometrial sarcomas of the uterus.", "content": "38 endometrial sarcomas were studied light microscopically, 5 of them additionally with the electron microscope. According to their histological appearance these tumours were classified as homologous stromal sarcomas (13 cases), pure heterologous (4) and mixed mesodermal sarcomas (21). The ultrastructure is described with reference to the cytoplasmic differentiation of the tumour cells. A basic immature cell type was present in all endometrial sarcomas irrespective whether they were of pure homologous or of mixed type. In regard to the striking similarity between this cell and cells of the early proliferating endometrium an origin of all endometrial sarcomas from immature stromal cell is suggested. The mixed tumours contain a number of highly differentiated cells like smooth muscle cells, rhabdomyoblasts, fibroblasts etc. As there was a number of cells intermediate in cytoplasmic appearances between immature and differentiated end stages it seems likely that the latter develop from the former. Thus the undifferentiated cell represents the stem cell from which the differentiation processes of all cell lines take their origin. A transition from neoplastic epithelium to neoplastic mesenchyme could not be demonstrated in thed that the mixed epithelial-mesenchymal endometrial tumours originate by a simultaneous malignant transformation of cells with a fixed differentiation potency.", "contents": "A light and electron microscopic study of endometrial sarcomas of the uterus. 38 endometrial sarcomas were studied light microscopically, 5 of them additionally with the electron microscope. According to their histological appearance these tumours were classified as homologous stromal sarcomas (13 cases), pure heterologous (4) and mixed mesodermal sarcomas (21). The ultrastructure is described with reference to the cytoplasmic differentiation of the tumour cells. A basic immature cell type was present in all endometrial sarcomas irrespective whether they were of pure homologous or of mixed type. In regard to the striking similarity between this cell and cells of the early proliferating endometrium an origin of all endometrial sarcomas from immature stromal cell is suggested. The mixed tumours contain a number of highly differentiated cells like smooth muscle cells, rhabdomyoblasts, fibroblasts etc. As there was a number of cells intermediate in cytoplasmic appearances between immature and differentiated end stages it seems likely that the latter develop from the former. Thus the undifferentiated cell represents the stem cell from which the differentiation processes of all cell lines take their origin. A transition from neoplastic epithelium to neoplastic mesenchyme could not be demonstrated in thed that the mixed epithelial-mesenchymal endometrial tumours originate by a simultaneous malignant transformation of cells with a fixed differentiation potency."} {"id": "PMID:171829", "title": "[Cylindroma of the breast. A histochemical and histogenetic study (author's transl)].", "content": "The histochemical study of mucopolysaccharide components of the ground substance of the cylindroma lends force to their epithelial origine. The myoepithelial cell, which is ectodermal in origin, plays an essential role in their secretion. Silver impregnation of normal and dysplastic breast illustrates the secretory function of myoepithelial cells and their possible implication in the histogenesis of cylindroma.", "contents": "[Cylindroma of the breast. A histochemical and histogenetic study (author's transl)]. The histochemical study of mucopolysaccharide components of the ground substance of the cylindroma lends force to their epithelial origine. The myoepithelial cell, which is ectodermal in origin, plays an essential role in their secretion. Silver impregnation of normal and dysplastic breast illustrates the secretory function of myoepithelial cells and their possible implication in the histogenesis of cylindroma."} {"id": "PMID:171830", "title": "[On the etiology of spindle-shaped acid-fast bodies in the human spleen (author's transl)].", "content": "Spindle-shaped acid-fast bodies have been identified only in lymph nodes till now. Their nature and their origin remained unclear. We have also found these bodies in the human spleen. Their staining reactions and their correlations to age, sex, weight of spleen, and to hemosiderin deposits were examined. They have been encountered in 50% of cases of hereditary spherocytosis and in 41.7% of cases of traumatic rupture of the spleen--but only in 2.3% of all other cases of groups of various other disorders. We conclude from our results that: 1. The spindle-shaped acid-fast bodies are made of ceroid. 2. They are not causative organisms and therefore cannot be of importance in the etiology of sarcoidosis. 3. They derive from increased destruction of erythrocytes. 4. They originate due to oxidative polymerization of membrane lipids. 5. They may also be found in absence of any fat-metabolism disturbance.", "contents": "[On the etiology of spindle-shaped acid-fast bodies in the human spleen (author's transl)]. Spindle-shaped acid-fast bodies have been identified only in lymph nodes till now. Their nature and their origin remained unclear. We have also found these bodies in the human spleen. Their staining reactions and their correlations to age, sex, weight of spleen, and to hemosiderin deposits were examined. They have been encountered in 50% of cases of hereditary spherocytosis and in 41.7% of cases of traumatic rupture of the spleen--but only in 2.3% of all other cases of groups of various other disorders. We conclude from our results that: 1. The spindle-shaped acid-fast bodies are made of ceroid. 2. They are not causative organisms and therefore cannot be of importance in the etiology of sarcoidosis. 3. They derive from increased destruction of erythrocytes. 4. They originate due to oxidative polymerization of membrane lipids. 5. They may also be found in absence of any fat-metabolism disturbance."} {"id": "PMID:171831", "title": "[The ultrastructure of fibrous and histiocytic skin tumors (dermatofibroma, dermatofibrosarcoma protuberans, fibroxanthoma, and histiocytoma) (author's transl)].", "content": "A report on the ultrastructure of the following skin tumors: dermatofibroma (7 cases), histiocytoma (4 cases), dermatofibrosarcoma protuberans (1 case), and fibroxanthoma (1 case). Because of their different ultrastructural characteristics a division into two groups is possible: one group of tumors would include dermatofibroma, dermatofibrosarcoma protuberans, and fibroxanthoma, where the formation of fibers is extensive and fibroblasts are suggested for its histogenesis. These types of tumor differ from histiocytoma, the cellular character of which is determined by a very pronounced phagocytosis and storage of lipid and hemosiderin; a histogenesis from histiocytes is probable. The nuclei of dermatofibroma and histiocytoma show a simple surfacedevelopment, whereas the nuclei of dermatofibrosarcoma protuberans and fibroxanthoma show multisegmented nuclei (\"labyrinth nuclei\"). In the case of dermatofibrosarcoma protuberans this kind of nuclear segmentation seems to be a morphologic correlate of its semimalignancy. Based on ultrastructural analysis a classification of these fiber-producing tumors into \"fibrous histiocytomas\" is not justified.", "contents": "[The ultrastructure of fibrous and histiocytic skin tumors (dermatofibroma, dermatofibrosarcoma protuberans, fibroxanthoma, and histiocytoma) (author's transl)]. A report on the ultrastructure of the following skin tumors: dermatofibroma (7 cases), histiocytoma (4 cases), dermatofibrosarcoma protuberans (1 case), and fibroxanthoma (1 case). Because of their different ultrastructural characteristics a division into two groups is possible: one group of tumors would include dermatofibroma, dermatofibrosarcoma protuberans, and fibroxanthoma, where the formation of fibers is extensive and fibroblasts are suggested for its histogenesis. These types of tumor differ from histiocytoma, the cellular character of which is determined by a very pronounced phagocytosis and storage of lipid and hemosiderin; a histogenesis from histiocytes is probable. The nuclei of dermatofibroma and histiocytoma show a simple surfacedevelopment, whereas the nuclei of dermatofibrosarcoma protuberans and fibroxanthoma show multisegmented nuclei (\"labyrinth nuclei\"). In the case of dermatofibrosarcoma protuberans this kind of nuclear segmentation seems to be a morphologic correlate of its semimalignancy. Based on ultrastructural analysis a classification of these fiber-producing tumors into \"fibrous histiocytomas\" is not justified."} {"id": "PMID:171856", "title": "[Quantitative cytochemical detection of enzymes in cultured cells following infection with Rous virus].", "content": "The method of visual quantitative estimation was employed to determine the index of enzymes activity in embryonal cells cultures infected with Rous virus. In early terms (1-7 days after infection) a moderate production of diformazane was noted in the presence of glucoso-6-phosphatiosomerase, phosphoglucomutase, pyruvatoxidase, NAD. H2- and NADP. H-2-diaphorase, other enzymes showing no distinquishable deviations in the activity, as compared with the normal culture. In later terms (13-27 days) during the proliferation of the transformed cells there was found an increased level of the glycolysis enzymes activity, pentose cycle, hydrolysis of ortho-phosphoric acid monoethers and reduced lemon acid cycle and tissue respiration. Cytoplasmatic vacuoles formed in the transformed cells seem to represent hypertrophic lysosomes and phagolysosomes.", "contents": "[Quantitative cytochemical detection of enzymes in cultured cells following infection with Rous virus]. The method of visual quantitative estimation was employed to determine the index of enzymes activity in embryonal cells cultures infected with Rous virus. In early terms (1-7 days after infection) a moderate production of diformazane was noted in the presence of glucoso-6-phosphatiosomerase, phosphoglucomutase, pyruvatoxidase, NAD. H2- and NADP. H-2-diaphorase, other enzymes showing no distinquishable deviations in the activity, as compared with the normal culture. In later terms (13-27 days) during the proliferation of the transformed cells there was found an increased level of the glycolysis enzymes activity, pentose cycle, hydrolysis of ortho-phosphoric acid monoethers and reduced lemon acid cycle and tissue respiration. Cytoplasmatic vacuoles formed in the transformed cells seem to represent hypertrophic lysosomes and phagolysosomes."} {"id": "PMID:171861", "title": "[Tumours of the corpus callosum in the anglogram (author's transl)].", "content": "On account of the median location of tumours of the corpus callosum, serial angiography reveals displacements only at an advanced stage. In many cases there is no lateral displacement of the anterior cerebral artery and a lateral angiogram of the pericallosal artery does not reveal tumours of the corpus callosum, especially if they are associated with a vascular pattern characteristic of arteriosclerosis or hydrocephalus. The deep mid-line veins are not consistently displaced. A differentiation of the vascular pattern associated with small tumours of the corpus callosum from normal variations may be problematic. The inner veins cannot be visualised sometimes on account of increased intracranial pressure and a slowing of the circulation.", "contents": "[Tumours of the corpus callosum in the anglogram (author's transl)]. On account of the median location of tumours of the corpus callosum, serial angiography reveals displacements only at an advanced stage. In many cases there is no lateral displacement of the anterior cerebral artery and a lateral angiogram of the pericallosal artery does not reveal tumours of the corpus callosum, especially if they are associated with a vascular pattern characteristic of arteriosclerosis or hydrocephalus. The deep mid-line veins are not consistently displaced. A differentiation of the vascular pattern associated with small tumours of the corpus callosum from normal variations may be problematic. The inner veins cannot be visualised sometimes on account of increased intracranial pressure and a slowing of the circulation."} {"id": "PMID:171862", "title": "Cyclic adenosine-3',5-monophosphate concentration and enzyme activities of cerebrospinal fluid in meningitis of children.", "content": "The concentration of cyclic adenosine-3',5'-monophosphate (cAMP) and the activities of some enzymes of 29 children were measured from cerebrospinal fluid (CSF) and plasma at various stages of meningitis. The CSF cAMP values in acute untreated phase of aseptic and purulent meningitis were equal, but significantly higher than those of convalescent children with no pathological clinical or laboratory findings. During the whole course (up to 2 weeks) of antimicrobial treatment of the purulent meningitis CSF cAMP concentration was higher than in the convalescent phase. Of the CSF enzymes studied, the lactic dehydrogenase activity seemed to be the best indicator of changing stages of meningitis. It was clearly elevated in the acute, untreated phase of purulent meningitis then decreasing during the course of treatment. In aseptic meningitis this activity was at the normal level and the activities of creatine kinase and acid phosphatase behaved similarly. The plasma cAMP concentrations in the acute phase of purulent meningitis were in the same range as in the CSF. During the treatment no significant changes were seen. The enzyme activities in the plasma were normal. The CSF cAMP level seems to be a sensitive indicator of metabolic disturbances in meningitis and may serve as a diagnostic aid.", "contents": "Cyclic adenosine-3',5-monophosphate concentration and enzyme activities of cerebrospinal fluid in meningitis of children. The concentration of cyclic adenosine-3',5'-monophosphate (cAMP) and the activities of some enzymes of 29 children were measured from cerebrospinal fluid (CSF) and plasma at various stages of meningitis. The CSF cAMP values in acute untreated phase of aseptic and purulent meningitis were equal, but significantly higher than those of convalescent children with no pathological clinical or laboratory findings. During the whole course (up to 2 weeks) of antimicrobial treatment of the purulent meningitis CSF cAMP concentration was higher than in the convalescent phase. Of the CSF enzymes studied, the lactic dehydrogenase activity seemed to be the best indicator of changing stages of meningitis. It was clearly elevated in the acute, untreated phase of purulent meningitis then decreasing during the course of treatment. In aseptic meningitis this activity was at the normal level and the activities of creatine kinase and acid phosphatase behaved similarly. The plasma cAMP concentrations in the acute phase of purulent meningitis were in the same range as in the CSF. During the treatment no significant changes were seen. The enzyme activities in the plasma were normal. The CSF cAMP level seems to be a sensitive indicator of metabolic disturbances in meningitis and may serve as a diagnostic aid."} {"id": "PMID:171865", "title": "Spontaneous variations in the cell population of a T-cell lymphoma during tissue culture and transplantation.", "content": "Immunologically induced T-cell lymphomas were kept for long period fo time in isotransplantation and in tissue culture. Initially, a certain number of cells within the tumor showed differentiation towards histiocytes. These disappeared completely after about the twentieth graft generation when the tumor changed toward a more atypical and more uniform neoplasm. That change was correlated with a decrease in transplantability, a limited growth in tissue culture, and a decrease in density of theta antigens on tumor cell membranes. While the original tumor and early grafts contained occasional C-type particles, these were never demonstrated in late tumor grafts. The possible implications of these changes are discussed.", "contents": "Spontaneous variations in the cell population of a T-cell lymphoma during tissue culture and transplantation. Immunologically induced T-cell lymphomas were kept for long period fo time in isotransplantation and in tissue culture. Initially, a certain number of cells within the tumor showed differentiation towards histiocytes. These disappeared completely after about the twentieth graft generation when the tumor changed toward a more atypical and more uniform neoplasm. That change was correlated with a decrease in transplantability, a limited growth in tissue culture, and a decrease in density of theta antigens on tumor cell membranes. While the original tumor and early grafts contained occasional C-type particles, these were never demonstrated in late tumor grafts. The possible implications of these changes are discussed."} {"id": "PMID:171864", "title": "Neurocristopathy, neuroendocrine pathology and the APUD concept.", "content": "The neurosecretory cells of the hypothalamus, and the cells of the pituitary gland and the pineal, are here grouped together as a central neuroendocrine division of the APUD series. The larger, peripheral division comprises the remainder of the original series. All the cells are proven or presumptive derivatives of neuroectoderm so that, with the present exception of the parathyroid gland and its products, peptide hormone endocrinology becomes neuroendocrinology. It follows that the pathology of the APUD cell series must be regarded as neuroendocrine and it is suggested that it can best be expressed by the term neurocristopathy (Bolande, 1974). Tumours of the series, properly neurocristomas, are preferably called apudomas because their common cytochemical (APUD) and ultrastructural characteristics provide the pathologist with a ready means of diagnosis.", "contents": "Neurocristopathy, neuroendocrine pathology and the APUD concept. The neurosecretory cells of the hypothalamus, and the cells of the pituitary gland and the pineal, are here grouped together as a central neuroendocrine division of the APUD series. The larger, peripheral division comprises the remainder of the original series. All the cells are proven or presumptive derivatives of neuroectoderm so that, with the present exception of the parathyroid gland and its products, peptide hormone endocrinology becomes neuroendocrinology. It follows that the pathology of the APUD cell series must be regarded as neuroendocrine and it is suggested that it can best be expressed by the term neurocristopathy (Bolande, 1974). Tumours of the series, properly neurocristomas, are preferably called apudomas because their common cytochemical (APUD) and ultrastructural characteristics provide the pathologist with a ready means of diagnosis."} {"id": "PMID:171866", "title": "[The evaluation of the cyclophosphamide sensitivity of human tumours by determining the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumor cells in vitro in presence of 4-hydroxycyclophosphamide (author's transl)].", "content": "A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound.", "contents": "[The evaluation of the cyclophosphamide sensitivity of human tumours by determining the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumor cells in vitro in presence of 4-hydroxycyclophosphamide (author's transl)]. A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound."} {"id": "PMID:171867", "title": "[Cardiac glomus tumor. Light- and electron microscopic investigations (author's transl)].", "content": "A cardiac glomus tumor, first described by Masson, was observed in a 28 year old woman who presented symptoms of cardiac dysfunction. Electron microscopic studies disclose a wide range of differentiation of glomus cells from smooth muscle cells to epitheloid cells. The common feature of both cell types include cytoplasmic microfibrils, fusiform condensations and small vesicles. The endothelial cells also show some structural similarities to these glomus cells. The histogenesis of this cardiac tumor is discussed on the basis of its ultrastructure and its uncommon localization. It is concluded that cardiac glomus tumors arise from primitive mesenchymal cells.", "contents": "[Cardiac glomus tumor. Light- and electron microscopic investigations (author's transl)]. A cardiac glomus tumor, first described by Masson, was observed in a 28 year old woman who presented symptoms of cardiac dysfunction. Electron microscopic studies disclose a wide range of differentiation of glomus cells from smooth muscle cells to epitheloid cells. The common feature of both cell types include cytoplasmic microfibrils, fusiform condensations and small vesicles. The endothelial cells also show some structural similarities to these glomus cells. The histogenesis of this cardiac tumor is discussed on the basis of its ultrastructure and its uncommon localization. It is concluded that cardiac glomus tumors arise from primitive mesenchymal cells."} {"id": "PMID:171868", "title": "Study of globular bodies found in hepatomas of Swiss mice.", "content": "In spontaneous hepatomas of Swiss mice a great number of eosinophilic globular bodies was observed without cirrhosis. Electron microscopy revealed their protein nature and origin from the rough endoplasmic reticulum cisternae.", "contents": "Study of globular bodies found in hepatomas of Swiss mice. In spontaneous hepatomas of Swiss mice a great number of eosinophilic globular bodies was observed without cirrhosis. Electron microscopy revealed their protein nature and origin from the rough endoplasmic reticulum cisternae."} {"id": "PMID:171869", "title": "Increasing occurence of tumour cell -- tumour cell emperipolesis in the regenerating JB-1 ascites tumour.", "content": "During the investigation of JB-1 ascites tumour cells in recurrent growth several cases of emperiopolesis were observed. Different types of emperipolesis are presented. Light microscopical serial sections, autoradiography and transmission electron microscopy indicate that the cells involved in emperipolesis are separate cells, and the authors suggest that cytopagocytosis is the initial mechanism in the development of emperipolesis.", "contents": "Increasing occurence of tumour cell -- tumour cell emperipolesis in the regenerating JB-1 ascites tumour. During the investigation of JB-1 ascites tumour cells in recurrent growth several cases of emperiopolesis were observed. Different types of emperipolesis are presented. Light microscopical serial sections, autoradiography and transmission electron microscopy indicate that the cells involved in emperipolesis are separate cells, and the authors suggest that cytopagocytosis is the initial mechanism in the development of emperipolesis."} {"id": "PMID:171870", "title": "The kininase activity of Ehrlichs' ascites solid tumor after treatment with oncolytic clostridia.", "content": "For the first time the effect of bacterial kininases of Cl. oncolyticum M 55 ATCC 13.732 could be demonstrated in the tumor itself. This is shown by an increased degradation of kinins by spore-treated tumor tissue in comparison with respective controls. The results indicate the influence of kininases on the capillary circulation of the tumor tissue as one of the fundamental reactions of oncolysis.", "contents": "The kininase activity of Ehrlichs' ascites solid tumor after treatment with oncolytic clostridia. For the first time the effect of bacterial kininases of Cl. oncolyticum M 55 ATCC 13.732 could be demonstrated in the tumor itself. This is shown by an increased degradation of kinins by spore-treated tumor tissue in comparison with respective controls. The results indicate the influence of kininases on the capillary circulation of the tumor tissue as one of the fundamental reactions of oncolysis."} {"id": "PMID:171871", "title": "[Transplacental oncogenic effect of ethylnitrosourea in rabbits (author's transl)].", "content": "50 mg/kg ethylnitrosourea (ENU) per dose, diluted in a 0.9%NaCl/1%NaH2PO4 solution (pH 6.2) were administered intravenously to three pregnant rabbits. The injections were carried out on the following days of gestation: 21., 26., and 30./21., 25., and 31./22., 25., and 30. From the total offspring (22), 16 rabbits could be raised. In 12 animals, kidney tumours were observed after a latent period of 2--2 1/2 years. The induced tumours are generally composed of both epithelial and mesenchymal tissue elements. Two tumours of the series are of a pure epithelial or a pure mesenchymal nature respectively. In most of the mixed tumours, classified as Adenocarcino-Sarcomas (10), the epithelial and mesenchymal elements are closely integrated, sometimes one component predominated over the other one. Histologically the ENU-induced mixed tumours of kidney in rabbits and the \"dysontogenetic\" kidney tumours of children (WILMS) show comparable structural characteristics.", "contents": "[Transplacental oncogenic effect of ethylnitrosourea in rabbits (author's transl)]. 50 mg/kg ethylnitrosourea (ENU) per dose, diluted in a 0.9%NaCl/1%NaH2PO4 solution (pH 6.2) were administered intravenously to three pregnant rabbits. The injections were carried out on the following days of gestation: 21., 26., and 30./21., 25., and 31./22., 25., and 30. From the total offspring (22), 16 rabbits could be raised. In 12 animals, kidney tumours were observed after a latent period of 2--2 1/2 years. The induced tumours are generally composed of both epithelial and mesenchymal tissue elements. Two tumours of the series are of a pure epithelial or a pure mesenchymal nature respectively. In most of the mixed tumours, classified as Adenocarcino-Sarcomas (10), the epithelial and mesenchymal elements are closely integrated, sometimes one component predominated over the other one. Histologically the ENU-induced mixed tumours of kidney in rabbits and the \"dysontogenetic\" kidney tumours of children (WILMS) show comparable structural characteristics."} {"id": "PMID:171872", "title": "In-vitro demonstration of cell-mediated immunity to vaccinia virus in man.", "content": "Cell mediated immunity to vaccinia virus in man was studied by lymphocyte transformation. Vaccinia antigen, propagated on BHK-21 and Vero cells, could be used successfully for in-vitro testing after partial purification as well as crude infectious homogenates. Vaccinia antigen preparations were effective both in the infective and the inactivated state. Inactivation was usually accompanied with a certain loss of stimulating activity. Development of cell mediated immune response in-vitro after first vaccination was investigated in 17 adults. Vaccinia virus specific lymphocyte transformation was seen in the second week after vaccination in all cases. Following revaccination no increase of lymphocyte transformation ratio could be observed in 11 persons studied. At the same time the titers of humoral antibodies were elevated.", "contents": "In-vitro demonstration of cell-mediated immunity to vaccinia virus in man. Cell mediated immunity to vaccinia virus in man was studied by lymphocyte transformation. Vaccinia antigen, propagated on BHK-21 and Vero cells, could be used successfully for in-vitro testing after partial purification as well as crude infectious homogenates. Vaccinia antigen preparations were effective both in the infective and the inactivated state. Inactivation was usually accompanied with a certain loss of stimulating activity. Development of cell mediated immune response in-vitro after first vaccination was investigated in 17 adults. Vaccinia virus specific lymphocyte transformation was seen in the second week after vaccination in all cases. Following revaccination no increase of lymphocyte transformation ratio could be observed in 11 persons studied. At the same time the titers of humoral antibodies were elevated."} {"id": "PMID:171873", "title": "[Transferrin variants: significance and identification in paternity cases (author's transl)].", "content": "Transferrin phenotypes were determined in 3380 sera of unrelated persons of the western region of Germany with 97.60 percent for TfC and 2.40 percent for Tf variants. Identification was achieved by immunochemical means or through autoradiography. Relative mobilities in some variants were measured using Tf B2C (0.7) as reference. Application of Tf variants is demonstrated in paternity cases.", "contents": "[Transferrin variants: significance and identification in paternity cases (author's transl)]. Transferrin phenotypes were determined in 3380 sera of unrelated persons of the western region of Germany with 97.60 percent for TfC and 2.40 percent for Tf variants. Identification was achieved by immunochemical means or through autoradiography. Relative mobilities in some variants were measured using Tf B2C (0.7) as reference. Application of Tf variants is demonstrated in paternity cases."} {"id": "PMID:171874", "title": "[Fibrillar and tubular fine structures in the cytoplasm of Entamoeba histolytica (author's transl)].", "content": "The electron-microscopical study of conventional fixed and contrasted Entamoeba histolytica-trophozoites from Diamonds monoxenic TTY-medium revealed \"thick fibrils\" in the vesicular cytoplasm of the parasites. They are 9-14 nm in diameter and are therefore considered to be myosin-like filaments, that are spread mainly in the tail or the uroid of the moving ameba. No association with microfilaments (MF) or other organelles could be observed. During the same investigation microtubules (MT) of variable length are described having a diameter of 35 nm, surrounded by a 19-25 nm wide capsule. They are distributed singly or in bundles with a maximal diameter of 350 nm. Some of the MT were coiled up to a helical shape.", "contents": "[Fibrillar and tubular fine structures in the cytoplasm of Entamoeba histolytica (author's transl)]. The electron-microscopical study of conventional fixed and contrasted Entamoeba histolytica-trophozoites from Diamonds monoxenic TTY-medium revealed \"thick fibrils\" in the vesicular cytoplasm of the parasites. They are 9-14 nm in diameter and are therefore considered to be myosin-like filaments, that are spread mainly in the tail or the uroid of the moving ameba. No association with microfilaments (MF) or other organelles could be observed. During the same investigation microtubules (MT) of variable length are described having a diameter of 35 nm, surrounded by a 19-25 nm wide capsule. They are distributed singly or in bundles with a maximal diameter of 350 nm. Some of the MT were coiled up to a helical shape."} {"id": "PMID:171875", "title": "Virulence of bacteria-associated, Crithidia-associated, and axenic Entamoeba histolytica: experimental hamster liver infections with strains from patients and carriers.", "content": "Experimental infections of the hamster liver were carried out with five strains from patients with clinical amoebiasis and ten strains from asymptomatic carriers. Inocula of comparatively small size (12000-36000 amoebae) were injected under the liver capsule. 1. The virulence of the patient strains varied from 21-96% (see article) and declined sharply within 7-15 weeks after elimination of the associated bacterial flora. The virulence of the carrier strains varied from 0-100%, probably fluctuating with changes in the concomitant bacterial flora (Table 1). 2. The interrelation between size of inoculum, period of bacteria-free growth, and virulence was demonstrated with a Crithidia-associated patient strains (Table 2). 3. A patient strain showed a faster decrease of virulence during axenic than in Crithidia-associated cultivation (Table 3). 4. Two successive passages through hamster liver resulted in a marked increase of virulence of two bacteria-free strains, lasting for several months (Table 4). 5. A significant enhancement of virulence of Crithidia-associated and axenic amoebae by reassociation with a mixed bacterial flora during two weeks, followed by elimination of the bacteria, was demonstrated with two strains. The restored virulence was lost again within a few weeks (Table 5). 6. The virulence of an attenuated patient strain did not become manifest by adding large numbers of dead amoebae to the inoculum (Table 6). 7. The pathology of the different lesions caused in the hamster liver by the amoebae is described, including one of a granulomatous type, frequently found after inoculation with bacteria-free amoebae. 8. In an attempt to explain the occurrence of strains differing in pathogenicity an hypothesis is put forward based on the idea of selection of virulence and avirulent amoebae.", "contents": "Virulence of bacteria-associated, Crithidia-associated, and axenic Entamoeba histolytica: experimental hamster liver infections with strains from patients and carriers. Experimental infections of the hamster liver were carried out with five strains from patients with clinical amoebiasis and ten strains from asymptomatic carriers. Inocula of comparatively small size (12000-36000 amoebae) were injected under the liver capsule. 1. The virulence of the patient strains varied from 21-96% (see article) and declined sharply within 7-15 weeks after elimination of the associated bacterial flora. The virulence of the carrier strains varied from 0-100%, probably fluctuating with changes in the concomitant bacterial flora (Table 1). 2. The interrelation between size of inoculum, period of bacteria-free growth, and virulence was demonstrated with a Crithidia-associated patient strains (Table 2). 3. A patient strain showed a faster decrease of virulence during axenic than in Crithidia-associated cultivation (Table 3). 4. Two successive passages through hamster liver resulted in a marked increase of virulence of two bacteria-free strains, lasting for several months (Table 4). 5. A significant enhancement of virulence of Crithidia-associated and axenic amoebae by reassociation with a mixed bacterial flora during two weeks, followed by elimination of the bacteria, was demonstrated with two strains. The restored virulence was lost again within a few weeks (Table 5). 6. The virulence of an attenuated patient strain did not become manifest by adding large numbers of dead amoebae to the inoculum (Table 6). 7. The pathology of the different lesions caused in the hamster liver by the amoebae is described, including one of a granulomatous type, frequently found after inoculation with bacteria-free amoebae. 8. In an attempt to explain the occurrence of strains differing in pathogenicity an hypothesis is put forward based on the idea of selection of virulence and avirulent amoebae."} {"id": "PMID:171883", "title": "[Secondary anemorrhea in processes in the sella region].", "content": "The authors report on 36 patients suffering from a tumor in the chiasm-sella-turcica region and their symptoms. The secondary amenorrhea and the disturbances of cycle are the first symptoms in 19 women from altogether 26 women in the stages of live from 14 to 50 years. It is commendable to take the expansive intracranial process in the chiams-sella-turcica region into consideration by the statement of the differential diagnosis of the secondary amenorrhea.", "contents": "[Secondary anemorrhea in processes in the sella region]. The authors report on 36 patients suffering from a tumor in the chiasm-sella-turcica region and their symptoms. The secondary amenorrhea and the disturbances of cycle are the first symptoms in 19 women from altogether 26 women in the stages of live from 14 to 50 years. It is commendable to take the expansive intracranial process in the chiams-sella-turcica region into consideration by the statement of the differential diagnosis of the secondary amenorrhea."} {"id": "PMID:171884", "title": "[The hidradenoma of the vulva].", "content": "The hidradenoma of vulva is a rare tumor. After description histogenesis and microscopic appearance demonstrated histological difficulties. An exact microscopic diagnois is necessary because the hidradenoma is a benign tumor.", "contents": "[The hidradenoma of the vulva]. The hidradenoma of vulva is a rare tumor. After description histogenesis and microscopic appearance demonstrated histological difficulties. An exact microscopic diagnois is necessary because the hidradenoma is a benign tumor."} {"id": "PMID:171885", "title": "[Comparative studies on the action of chlorine and ozone on polioviruses in the reprocessing of drinking water in Essen (author's transl)].", "content": "The present study was performed in order to evaluate comparatively the inactivation of polio virus type I strains (wild type and attenuated) by means of chlorine and ozone. Polio virus type I was chosen with regard to its epidemiological behaviour and high stability in drinking-water and sewage lines. In view of the lack of propagation techniques, hepatitis viruses A and B, unfortunately, could not be used for these experiments. The experiments were done under laboratory conditions only, and not in the water recovery plant because of hygienic reasons. Defined quantities of disinfectants were examined for their virus-inactivating effect in water without redox-potential (double-distilled water), water with low defined redox-potential (double-distilled water + KOH), previously chlorinated water with a residual chlorine content of 0.03 mg chlorine per liter (tap water) and water with a high redox-potential (well water from the drinking-water plant). Time-course studies were performed, both with chlorine and ozone, in order to evaluate the characteristics of the inactivation procedure. The experimental conditions chosen varied from experiment to experiment to obtain relevant conclusions for the practice. On the basis of our results, and taking into account the quantitative differences in effect, chlorine and ozone principially can be considered equivalent in their action of virus-disinfection. Both, the initial rate and the kinetics of virus disinfection are really identical. Both disinfectants are dependant on the condition of the water (redox-potential, pH etc.) to a great extent in their efficacy. Therefore, a decision of whether or not ozone should substitute for chlorine for the drinking-water supply in Essen cannot be drawn on the basis of virological experiments. This decision, then, depends more or less on other questions - such as relative costs and practicability of the ozonization on a large technical scale. The safety risk and technical reliability of the ozonization process is of particular significance. In the present condition of the Essen reservoir water, a good virus disinfection can be expected already with 1.0 to 1.5 mg ozone/liter (dissolved!); such a concentration guarantees very little residual ozone and, thus, makes then this procedure technically feasible. Continuous checking of the redox-potential and the amount of the ozone added is necessary. With regard to a continuous supply of ozone, the dependence on current supply must be guaranteed. Ozonization of water, probably by the cleavage of humic acid, promotes bacterial recontamination of the drinking-water in the city taps(Stalder und Klosterk\u00f6tter, 45). Therefore only a combined pre-ozonization with subsequent chlorination would guarantee, both, safety and improvement of the cosmetical conditions of the drinking-water. Such a combination would be feasible with highly reduced amounts of ozone and chlorine.", "contents": "[Comparative studies on the action of chlorine and ozone on polioviruses in the reprocessing of drinking water in Essen (author's transl)]. The present study was performed in order to evaluate comparatively the inactivation of polio virus type I strains (wild type and attenuated) by means of chlorine and ozone. Polio virus type I was chosen with regard to its epidemiological behaviour and high stability in drinking-water and sewage lines. In view of the lack of propagation techniques, hepatitis viruses A and B, unfortunately, could not be used for these experiments. The experiments were done under laboratory conditions only, and not in the water recovery plant because of hygienic reasons. Defined quantities of disinfectants were examined for their virus-inactivating effect in water without redox-potential (double-distilled water), water with low defined redox-potential (double-distilled water + KOH), previously chlorinated water with a residual chlorine content of 0.03 mg chlorine per liter (tap water) and water with a high redox-potential (well water from the drinking-water plant). Time-course studies were performed, both with chlorine and ozone, in order to evaluate the characteristics of the inactivation procedure. The experimental conditions chosen varied from experiment to experiment to obtain relevant conclusions for the practice. On the basis of our results, and taking into account the quantitative differences in effect, chlorine and ozone principially can be considered equivalent in their action of virus-disinfection. Both, the initial rate and the kinetics of virus disinfection are really identical. Both disinfectants are dependant on the condition of the water (redox-potential, pH etc.) to a great extent in their efficacy. Therefore, a decision of whether or not ozone should substitute for chlorine for the drinking-water supply in Essen cannot be drawn on the basis of virological experiments. This decision, then, depends more or less on other questions - such as relative costs and practicability of the ozonization on a large technical scale. The safety risk and technical reliability of the ozonization process is of particular significance. In the present condition of the Essen reservoir water, a good virus disinfection can be expected already with 1.0 to 1.5 mg ozone/liter (dissolved!); such a concentration guarantees very little residual ozone and, thus, makes then this procedure technically feasible. Continuous checking of the redox-potential and the amount of the ozone added is necessary. With regard to a continuous supply of ozone, the dependence on current supply must be guaranteed. Ozonization of water, probably by the cleavage of humic acid, promotes bacterial recontamination of the drinking-water in the city taps(Stalder und Klosterk\u00f6tter, 45). Therefore only a combined pre-ozonization with subsequent chlorination would guarantee, both, safety and improvement of the cosmetical conditions of the drinking-water. Such a combination would be feasible with highly reduced amounts of ozone and chlorine."} {"id": "PMID:171886", "title": "[Histological diagnosis and therapy of rare breast neoplasms].", "content": "Occasional rare benign and malignant breast tumours present diagnostical difficulties, how a report on 8 rare forms of tumours among 564 breast rumors (351 benign, 213 malignant) of the years 1965--1972 at the Universit\u00e4ts-Frauenklinik Greifswald shows. We found among 351 benign breast tumours 2 rare forms: 1 tubular adenoma and 1 nodular lymphoreticulosis. We diagnosed among 213 malignant breast tumours 6 rare tumour-types: one at a case an unilateral respectively a bilateral noninvasive lobular carcinoma from the carcinoma-in-situ-type, 1 spindlecell- and 2 reticulosarcoma, which in one case the starting-point of the heterogeneous differentiated reticulosarcoma was obvious situated in a teratoid tumour. Last case dealt with a real cystosarcoma phylloides, of which oncological and terminological problems were additional discussed.", "contents": "[Histological diagnosis and therapy of rare breast neoplasms]. Occasional rare benign and malignant breast tumours present diagnostical difficulties, how a report on 8 rare forms of tumours among 564 breast rumors (351 benign, 213 malignant) of the years 1965--1972 at the Universit\u00e4ts-Frauenklinik Greifswald shows. We found among 351 benign breast tumours 2 rare forms: 1 tubular adenoma and 1 nodular lymphoreticulosis. We diagnosed among 213 malignant breast tumours 6 rare tumour-types: one at a case an unilateral respectively a bilateral noninvasive lobular carcinoma from the carcinoma-in-situ-type, 1 spindlecell- and 2 reticulosarcoma, which in one case the starting-point of the heterogeneous differentiated reticulosarcoma was obvious situated in a teratoid tumour. Last case dealt with a real cystosarcoma phylloides, of which oncological and terminological problems were additional discussed."} {"id": "PMID:171888", "title": "[Effects of diethyldithiocarbamate on the acute toxicity and the acetylcholinesterase inhibition by methylparathion in mice].", "content": "Acute toxicity of methylparathion male mice is reduced by DET in dose-range from 50 to 300 mg/kg. Mean survival time in LD100 range of methylparathion is significantly prolonged. Inhibition of AChE in vivo is reduced, too. The observed dose-effect-relations show an approx. 10-fold increase in equi-effective doses after DET-pretreatment. DET has no protective effect both in vivo and in vitro, if methylparathion is added to the brain homogenate of mice. As probable mechanism of action a change in methylparathion-metabolism induced by DET in the system of mixed functional oxidases is discussed.", "contents": "[Effects of diethyldithiocarbamate on the acute toxicity and the acetylcholinesterase inhibition by methylparathion in mice]. Acute toxicity of methylparathion male mice is reduced by DET in dose-range from 50 to 300 mg/kg. Mean survival time in LD100 range of methylparathion is significantly prolonged. Inhibition of AChE in vivo is reduced, too. The observed dose-effect-relations show an approx. 10-fold increase in equi-effective doses after DET-pretreatment. DET has no protective effect both in vivo and in vitro, if methylparathion is added to the brain homogenate of mice. As probable mechanism of action a change in methylparathion-metabolism induced by DET in the system of mixed functional oxidases is discussed."} {"id": "PMID:171889", "title": "Correlation between drug induced changes of acetylcholine release and acetylcholine fractions in rat brain.", "content": "After administration of eserine, a new acetylcholine (ACh) subfraction called f+ is formed in rat brain tissue. References and methods are given for the calculation of this subfraction, which can be isolated and determined only together with the so-called \"free\" ACh fraction. Alterations of the f+-ACh subfraction caused by barbital, urethane, pentetrazol, arecoline and scopolamine in telencephalon, cortex and striatum of rat brain are connected with changes of ACh concentrations determined in comparable releasing tests.", "contents": "Correlation between drug induced changes of acetylcholine release and acetylcholine fractions in rat brain. After administration of eserine, a new acetylcholine (ACh) subfraction called f+ is formed in rat brain tissue. References and methods are given for the calculation of this subfraction, which can be isolated and determined only together with the so-called \"free\" ACh fraction. Alterations of the f+-ACh subfraction caused by barbital, urethane, pentetrazol, arecoline and scopolamine in telencephalon, cortex and striatum of rat brain are connected with changes of ACh concentrations determined in comparable releasing tests."} {"id": "PMID:171890", "title": "[Antiviral thiosemicarbazone and related compounds. III. Quantitative relationships between structure and antiviral activity of isantin-beta-isothio-semicarbazone against mengo virus].", "content": "The virostatic activity of isatin-beta-isothiosemicarbazones can be described quantitatively by hydrophobic, electronic, and steric substituent constants using multivariate regression analysis. A preceding Free-Wilson analysis allows data smoothening, and thus improved adaptation. Predictions made on the basis of the quantitative structure-action relationships obtained could be confirmed experimentally by synthesizing and testing the corresponding compounds.", "contents": "[Antiviral thiosemicarbazone and related compounds. III. Quantitative relationships between structure and antiviral activity of isantin-beta-isothio-semicarbazone against mengo virus]. The virostatic activity of isatin-beta-isothiosemicarbazones can be described quantitatively by hydrophobic, electronic, and steric substituent constants using multivariate regression analysis. A preceding Free-Wilson analysis allows data smoothening, and thus improved adaptation. Predictions made on the basis of the quantitative structure-action relationships obtained could be confirmed experimentally by synthesizing and testing the corresponding compounds."} {"id": "PMID:171891", "title": "On the influence of fructose-6-phosphate, ammonium, ATP and AMP on the conformation of the phosphofructokinase from rabbit muscle.", "content": "By means of circular dichroism measurements in the range from 210-240 nm and 250-300 nm it is shown that conformational changes of the phosphofructokinase from rabbit muscle correlate with the action of effectors on the enzyme. The postulated active and inactive states differ in the secondary structure. Addition of activators causes a conformational change which is interpreted as the transition of the inactive into the active state. At 210-240 nm no reversion could be observed but at 250-300 nm there are some indications for at least partial reversion.", "contents": "On the influence of fructose-6-phosphate, ammonium, ATP and AMP on the conformation of the phosphofructokinase from rabbit muscle. By means of circular dichroism measurements in the range from 210-240 nm and 250-300 nm it is shown that conformational changes of the phosphofructokinase from rabbit muscle correlate with the action of effectors on the enzyme. The postulated active and inactive states differ in the secondary structure. Addition of activators causes a conformational change which is interpreted as the transition of the inactive into the active state. At 210-240 nm no reversion could be observed but at 250-300 nm there are some indications for at least partial reversion."} {"id": "PMID:171892", "title": "Serological analysis of an oncornavirus (PMF virus) detected in malignant permanent human cell lines.", "content": "Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.", "contents": "Serological analysis of an oncornavirus (PMF virus) detected in malignant permanent human cell lines. Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus."} {"id": "PMID:171893", "title": "Protamine inhibition of the oxidative phosphorylation in intact, cytochrome c-depleted and restored mitochondria.", "content": "On the basis of polarographic data it is shown that protamine has a biphasic effect on the respiration of intact mitochondria. At lower protamine concentrations respiration is stimulated and this combined with a decrease of the respiratory control index; at higher ones respiration is inhibited and respiratory control is lost. In cytochrome c-depleted and restored mitochondria protamine effect on oxidative phosphorylation is only inhibitory. Increasing cytochrome c concentrations restore respiration in protamine-treated cytochrome c depleted mitochondria but not the respiratory control. Binding of cytochrome c to mitochondria is studied by determining from Scatchard plots the number of high affinity binding sites (n) and their stability constants (K). In absence of protamine in intact mitochondria n = 2.7 and K = 4.67-10(6) M-1; in cotochrome c depleted mitochondria n = 4.7 and K = 5.16-10(6) M-1. In both types of mitochondria protamine decreases significantly n as well as K. These data show that protamine may affect oxidative phosphorylation by causing desorption of cytochrome c from the inner mitochondrial membrane.", "contents": "Protamine inhibition of the oxidative phosphorylation in intact, cytochrome c-depleted and restored mitochondria. On the basis of polarographic data it is shown that protamine has a biphasic effect on the respiration of intact mitochondria. At lower protamine concentrations respiration is stimulated and this combined with a decrease of the respiratory control index; at higher ones respiration is inhibited and respiratory control is lost. In cytochrome c-depleted and restored mitochondria protamine effect on oxidative phosphorylation is only inhibitory. Increasing cytochrome c concentrations restore respiration in protamine-treated cytochrome c depleted mitochondria but not the respiratory control. Binding of cytochrome c to mitochondria is studied by determining from Scatchard plots the number of high affinity binding sites (n) and their stability constants (K). In absence of protamine in intact mitochondria n = 2.7 and K = 4.67-10(6) M-1; in cotochrome c depleted mitochondria n = 4.7 and K = 5.16-10(6) M-1. In both types of mitochondria protamine decreases significantly n as well as K. These data show that protamine may affect oxidative phosphorylation by causing desorption of cytochrome c from the inner mitochondrial membrane."} {"id": "PMID:171894", "title": "Perchloric acid-soluble proteins and protein-bound hexoses in serum and tissues of normal, hypo-and hyperthyroid rats.", "content": "The total content of perchloric acid-soluble proteins (PCA-SP) and protein-bound hexoses (PBH) were studied in blood serum and tissues (liver, kidney, lung, brain) of normal, hypo- and hyperthyroid rats. The results obtained indicate that the hyperthyroid state induced an increase in both PCA-SP and PBH in blood serum and studied tissue homogenates, and hypothyreosis causes a decrease of total glycoproteins content in all studied materials. The results were counted per 1 g of protein and in this way the nonspecific effect of thyroid hormones on the protein metabolism had no influence on the measurements.", "contents": "Perchloric acid-soluble proteins and protein-bound hexoses in serum and tissues of normal, hypo-and hyperthyroid rats. The total content of perchloric acid-soluble proteins (PCA-SP) and protein-bound hexoses (PBH) were studied in blood serum and tissues (liver, kidney, lung, brain) of normal, hypo- and hyperthyroid rats. The results obtained indicate that the hyperthyroid state induced an increase in both PCA-SP and PBH in blood serum and studied tissue homogenates, and hypothyreosis causes a decrease of total glycoproteins content in all studied materials. The results were counted per 1 g of protein and in this way the nonspecific effect of thyroid hormones on the protein metabolism had no influence on the measurements."} {"id": "PMID:171895", "title": "[The effect of preparative pancreatic digestion with collagenase on the glucose stimulated insulin secretion of isolated Langerhans islets].", "content": "Pancreatic islets of wistar rats, isolated after 15 min of digestion with collagenase, secreted insulin in response to 15.0 mM glucose within 2 min and showed the typical sigmoidal glucose response during an incubation time of 15 and 60 min, respectively. Islets, isolated after 35 min of digestion with collagenase, responded with delay after stimulation with glucose (after 15 min of incubation), and are characterized by an increased \"release\" in the presence of 2.5 mM glucose.", "contents": "[The effect of preparative pancreatic digestion with collagenase on the glucose stimulated insulin secretion of isolated Langerhans islets]. Pancreatic islets of wistar rats, isolated after 15 min of digestion with collagenase, secreted insulin in response to 15.0 mM glucose within 2 min and showed the typical sigmoidal glucose response during an incubation time of 15 and 60 min, respectively. Islets, isolated after 35 min of digestion with collagenase, responded with delay after stimulation with glucose (after 15 min of incubation), and are characterized by an increased \"release\" in the presence of 2.5 mM glucose."} {"id": "PMID:171896", "title": "Pseudomonas cytochrome c peroxidase XI. Kinetics of the peroxidatic oxidation of Pseudomonas respiratory chain components.", "content": "The steady state kinetics of cytochrome c peroxidase from Pseudomonas aeruginosa (PaCCP) has been studied by initial velocity techniques using several cytochromes c (550 and 555 P. aeruginosa; 551 P. fluorescens) and Pseudomonas azurin as electron donors and hydrogen peroxide as electron acceptor. From the initial velocity patterns a sequential mechanism with compulsory substrate-binding order is proposed for PaCCP. A comparative kinetic study of the peroxidatic oxidation of cytochrome c-551 (P. aeruginosa) by yeast cytochrome c peroxidase was made to evaluate the significance of electrostatic interactions in complex formation between the enzyme and substrates.", "contents": "Pseudomonas cytochrome c peroxidase XI. Kinetics of the peroxidatic oxidation of Pseudomonas respiratory chain components. The steady state kinetics of cytochrome c peroxidase from Pseudomonas aeruginosa (PaCCP) has been studied by initial velocity techniques using several cytochromes c (550 and 555 P. aeruginosa; 551 P. fluorescens) and Pseudomonas azurin as electron donors and hydrogen peroxide as electron acceptor. From the initial velocity patterns a sequential mechanism with compulsory substrate-binding order is proposed for PaCCP. A comparative kinetic study of the peroxidatic oxidation of cytochrome c-551 (P. aeruginosa) by yeast cytochrome c peroxidase was made to evaluate the significance of electrostatic interactions in complex formation between the enzyme and substrates."} {"id": "PMID:171897", "title": "Subcutaneous mastectomy in 80 patients with breast tumours. Indications, surgical results and pathological findings.", "content": "Eighty patients were operated upon with subcutaneous mastectomy and reconstruction with prosthesis. Seventy operations were performed on both breasts. The indications used were carcinoma in situ in a previous biopsy, pronounced epithelial proliferations on at least two previous occasions or recurring fibrocystic disease after at least two previous biopsies. Since the autumn of 1971, the operation has been performed as a one-stage procedure and we have had few complications. The appearance of the breasts was evaluated at review 3-60 months after operation. Most patients found the results acceptable or good. The mamilla always lost its sensibility, but the sensibility of the remaining skin of the breast sometimes returned with time. Most of the patients were well satisfied with the procedure and thought it better than any other sort of treatment. The tissues removed were thoroughly studied. Changes in the breasts were often bilateral and pronounced epithelial proliferation and carcinoma in situ were fairly common. Invasive carcinoma was found in 2 instances. The importance of the histologic examination of removed tissues is stressed. A regular follow-up of these patients is important for assessing the value and the risks of subcutaneous mastectomy.", "contents": "Subcutaneous mastectomy in 80 patients with breast tumours. Indications, surgical results and pathological findings. Eighty patients were operated upon with subcutaneous mastectomy and reconstruction with prosthesis. Seventy operations were performed on both breasts. The indications used were carcinoma in situ in a previous biopsy, pronounced epithelial proliferations on at least two previous occasions or recurring fibrocystic disease after at least two previous biopsies. Since the autumn of 1971, the operation has been performed as a one-stage procedure and we have had few complications. The appearance of the breasts was evaluated at review 3-60 months after operation. Most patients found the results acceptable or good. The mamilla always lost its sensibility, but the sensibility of the remaining skin of the breast sometimes returned with time. Most of the patients were well satisfied with the procedure and thought it better than any other sort of treatment. The tissues removed were thoroughly studied. Changes in the breasts were often bilateral and pronounced epithelial proliferation and carcinoma in situ were fairly common. Invasive carcinoma was found in 2 instances. The importance of the histologic examination of removed tissues is stressed. A regular follow-up of these patients is important for assessing the value and the risks of subcutaneous mastectomy."} {"id": "PMID:171898", "title": "Assessment of gonadotrophin secretion in women with anorexia nervosa.", "content": "The LH and FSH secretions in 21 patients with anorexia nervosa were assessed by radioimmunoassay. On a single iv injection of 100 mug LH-releasing hormone (LH-RH), 8 patients showed LH response comparable to that of normal cyclic women in the follicular phase, and 5 patients showed excessive response. Although the remaining 8 patients showed almost no LH response, infusion of 400 mug LH-RH or daily im injections of LH-RH restored gonadotrophin responsiveness to LH-RH in all patients tested. The initial rise in LH during clomiphene citrate treatment was observed in 3 out of 5 patients, but the second peak of LH was found in only one patient. The initial suppression of LH following iv injection of conjugated oestrogen (Premarin) was observed in 9 out of 10 patients but a rebound increase comparable to that in normal cyclic women in the mid-follicular phase was found in only 3 patients. These results seem to suggest that impaired hypothalamic function is the cause of gonadotrophin deficiency and the resultant anovulation in most patients with anorexia nervosa.", "contents": "Assessment of gonadotrophin secretion in women with anorexia nervosa. The LH and FSH secretions in 21 patients with anorexia nervosa were assessed by radioimmunoassay. On a single iv injection of 100 mug LH-releasing hormone (LH-RH), 8 patients showed LH response comparable to that of normal cyclic women in the follicular phase, and 5 patients showed excessive response. Although the remaining 8 patients showed almost no LH response, infusion of 400 mug LH-RH or daily im injections of LH-RH restored gonadotrophin responsiveness to LH-RH in all patients tested. The initial rise in LH during clomiphene citrate treatment was observed in 3 out of 5 patients, but the second peak of LH was found in only one patient. The initial suppression of LH following iv injection of conjugated oestrogen (Premarin) was observed in 9 out of 10 patients but a rebound increase comparable to that in normal cyclic women in the mid-follicular phase was found in only 3 patients. These results seem to suggest that impaired hypothalamic function is the cause of gonadotrophin deficiency and the resultant anovulation in most patients with anorexia nervosa."} {"id": "PMID:171899", "title": "Human lymphocyte binding and deiodination of thyroid hormones in relation to thyroid function.", "content": "The human lymphocyte has been investigated regarding its function as a thyroid hormone target cell. Binding and deiodination of the thyroid hormones were determined after simultaneous incubation of 131I-labelled L-thyroxine (131I-T4) and 125I-labelled L-triiodothyronine (125I-T3) with lymphocytes from healthy subjects, from hyperthyroid and primary hypothyroid patients before and after treatment. The mean percentages of binding, 8.0 +/- 0.5 (mean +/- SEM) for 131I-T4, and 9.7 +/- 0.4 for 125I-T3 in the control group, were increased in the hyperthyroids to 10.1 +/- 0.4 and 12.7 +/- 0.6 respectively, and in the hypothyroids to 10.9 +/- 0.7 and 12.8 +/- 0.6. All elevated values returned to normal with successful treatment. The mean percentage of deiodination, 12.0 +/- 1.7 for 131I-T4, and 6.5 +/- 0.9 for 125I-T3 in the control group, showed a threefold increase in the hyperthyroid patients, to 35.9 +/- 3.2 and 20.2 +/- 1.9 respectively and remained unaltered in the hypothyroid patients. The values of successfully treated hyperthyroid patients were normal and those of the treated hypothyroid patients below normal.", "contents": "Human lymphocyte binding and deiodination of thyroid hormones in relation to thyroid function. The human lymphocyte has been investigated regarding its function as a thyroid hormone target cell. Binding and deiodination of the thyroid hormones were determined after simultaneous incubation of 131I-labelled L-thyroxine (131I-T4) and 125I-labelled L-triiodothyronine (125I-T3) with lymphocytes from healthy subjects, from hyperthyroid and primary hypothyroid patients before and after treatment. The mean percentages of binding, 8.0 +/- 0.5 (mean +/- SEM) for 131I-T4, and 9.7 +/- 0.4 for 125I-T3 in the control group, were increased in the hyperthyroids to 10.1 +/- 0.4 and 12.7 +/- 0.6 respectively, and in the hypothyroids to 10.9 +/- 0.7 and 12.8 +/- 0.6. All elevated values returned to normal with successful treatment. The mean percentage of deiodination, 12.0 +/- 1.7 for 131I-T4, and 6.5 +/- 0.9 for 125I-T3 in the control group, showed a threefold increase in the hyperthyroid patients, to 35.9 +/- 3.2 and 20.2 +/- 1.9 respectively and remained unaltered in the hypothyroid patients. The values of successfully treated hyperthyroid patients were normal and those of the treated hypothyroid patients below normal."} {"id": "PMID:171900", "title": "Oestradiol receptor levels in the human fallopian tube during the menstrual cycle.", "content": "The levels of cytoplasmic high-affinity oestradiol receptor sites were determined in the isthmus, isthmus-ampulla, ampulla and fimbria of human Fallopian tubes obtained from 23 women during the proliferative and secretory phase of the menstrual cycle and after menopause. Each segment was homogenized in 0.25 M sucrose and fractionated by differential centrifugation into an 800 g X 15 min nuclear pellet and a 100,000 g X 1 h cytoplasmic supernatant and pellet. The nuclear and cytoplasmic pellets were extracted with 0.01 M Tris/HCl pH 8.0 containing 0.25 M sucrose, 1 mM EDTA and 0.1 M KCl. The receptor levels were determined in the 100,000 g X 1 h supernatant (free receptors) and in the KCl extracts (bound receptors). Values are expressed per mug DNA. The concentration of receptors (total, free and bound) was significantly greater in the ampulla than in the isthmus in both phases of the menstrual cycle (P less than 0.001). The concentration of free receptors in the isthmus, isthmus-ampulla and ampulla obtained in the proliferative phase was not significantly different from that of the secretory phase. In the fimbria a significantly higher concentration (P less than 0.01) was observed in the proliferative phase. The bound receptors were significantly higher in all regions in the proliferative phase than in the secretory phase (P less than 0.01). As a consequence the concentration of total receptors was significantly greater along the tube in the proliferative phase (P less than 0.01). The levels of oestradiol in the nuclear pellet of each segment as measured by radioimmunoassay were significantly greater in the isthmic region (P less than 0.01) than in other regions of the tube. The inverse relationship between the concentration of oestradiol receptor sites and the nuclear levels of oestradiol along the Fallopian tube is discussed.", "contents": "Oestradiol receptor levels in the human fallopian tube during the menstrual cycle. The levels of cytoplasmic high-affinity oestradiol receptor sites were determined in the isthmus, isthmus-ampulla, ampulla and fimbria of human Fallopian tubes obtained from 23 women during the proliferative and secretory phase of the menstrual cycle and after menopause. Each segment was homogenized in 0.25 M sucrose and fractionated by differential centrifugation into an 800 g X 15 min nuclear pellet and a 100,000 g X 1 h cytoplasmic supernatant and pellet. The nuclear and cytoplasmic pellets were extracted with 0.01 M Tris/HCl pH 8.0 containing 0.25 M sucrose, 1 mM EDTA and 0.1 M KCl. The receptor levels were determined in the 100,000 g X 1 h supernatant (free receptors) and in the KCl extracts (bound receptors). Values are expressed per mug DNA. The concentration of receptors (total, free and bound) was significantly greater in the ampulla than in the isthmus in both phases of the menstrual cycle (P less than 0.001). The concentration of free receptors in the isthmus, isthmus-ampulla and ampulla obtained in the proliferative phase was not significantly different from that of the secretory phase. In the fimbria a significantly higher concentration (P less than 0.01) was observed in the proliferative phase. The bound receptors were significantly higher in all regions in the proliferative phase than in the secretory phase (P less than 0.01). As a consequence the concentration of total receptors was significantly greater along the tube in the proliferative phase (P less than 0.01). The levels of oestradiol in the nuclear pellet of each segment as measured by radioimmunoassay were significantly greater in the isthmic region (P less than 0.01) than in other regions of the tube. The inverse relationship between the concentration of oestradiol receptor sites and the nuclear levels of oestradiol along the Fallopian tube is discussed."} {"id": "PMID:171901", "title": "Hybridization of mouse leukemia virus c-DNA to mouse repeated DNA sequences.", "content": "Experiments of hybridization between mouse leukemia virus synthetic 3H-DNA probe and mouse main band and satellite DNAs indicate that there is not a higher concentration of viral sequences in the satellite DNA. On the contrary, viral sequences appear to be enriched in the fast renaturing intermediate main band DNA.", "contents": "Hybridization of mouse leukemia virus c-DNA to mouse repeated DNA sequences. Experiments of hybridization between mouse leukemia virus synthetic 3H-DNA probe and mouse main band and satellite DNAs indicate that there is not a higher concentration of viral sequences in the satellite DNA. On the contrary, viral sequences appear to be enriched in the fast renaturing intermediate main band DNA."} {"id": "PMID:171902", "title": "[Histochemical investigations on liver and kidney of the rat after intoxication with organophosphates (author's transl)].", "content": "Comparative histochemical investigations of the livers and kidneys of female Sprague-Dawley rats were made: 1. after intoxication with O-pinacolyl-methyl-phosphonylfluoride (Soman), O,O-diethyl-O-p-nitrophenylphosphate (Paraoxon, E 600); 2. after starvation of 24 to 36 h; 3. after hypoxia for 24 h. From the results it is concluded that the fatty degeneration of liver and kidney after PE.-intoxication is caused by intracellular hypoxia. No fatty degeneration of the organs was observed following deprivation of food for 36 h. A decreased level of cholin which might be caused by the intoxication with PE., and which could be the reason for the fatty degeneration was not found. This was indicated by the unaltered evidence of phosphatids in the intoxicated animals.", "contents": "[Histochemical investigations on liver and kidney of the rat after intoxication with organophosphates (author's transl)]. Comparative histochemical investigations of the livers and kidneys of female Sprague-Dawley rats were made: 1. after intoxication with O-pinacolyl-methyl-phosphonylfluoride (Soman), O,O-diethyl-O-p-nitrophenylphosphate (Paraoxon, E 600); 2. after starvation of 24 to 36 h; 3. after hypoxia for 24 h. From the results it is concluded that the fatty degeneration of liver and kidney after PE.-intoxication is caused by intracellular hypoxia. No fatty degeneration of the organs was observed following deprivation of food for 36 h. A decreased level of cholin which might be caused by the intoxication with PE., and which could be the reason for the fatty degeneration was not found. This was indicated by the unaltered evidence of phosphatids in the intoxicated animals."} {"id": "PMID:171903", "title": "[Histochemical and histological investigations on the vagina of the beagle she-dog during various functional conditions (author's transl)].", "content": "Histotopochemistry and histology of vaginal epithelium in female beagles were studied during oestrus, metoestrus-dioestrus, post partum period and at days 20, 30, 40, 50, 60 of pregnancy. During oestrus the epithelium is uniform throughout the whole vagina: it presents itself as a high, uncornified, stratified squamous epithelium with some glycogen and lipid droplets but devoid of leucocytes. The intercellular gaps of the stratum intermedium give strong reactions for ATPase and alkaline phosphatase. The activities of oxidoreductases studied decrease continuously from basal to apical. During gravidity, post partum period and metoestrus-dioestrus distinct morphological and histochemical differences can be stated between the cranial and caudal vaginal portions. Caudal vaginal epithelium outside oestrus remains of stratified squamous type. It exhibits strong mucification during pregnancy. The PAS-positive mucous substances prefer a position in the enlarged intercellular gaps of stratum intermedium and superficiale. During pregnancy the epithelium is relatively rich in acid and completely devoid of alkaline phosphatases. Outside oestrus the epithelium of the cranial vaginal region is a relatively flat, stratified columnar one and contains leucocytes with regularity. Also the cranial vaginal portion undergoes mucification during pregnancy with a maximum about day 33. The mucous material is situated intracellularly and not within the intercellular gaps. Further, larger intraepithelial mucus cysts are observed. Alkaline phosphatase is found during gravidity in the basal region and an adluminal border of the epithelium. The reactions for oxidoreductases are strongest in the columnar cell layer which shows more functional adaptations than the remainder of the epithelium. Histochemical tests for beta-D-glucuronidase and leucine aminopeptidase give negative results in the whole vagina during all different functional stages studied.", "contents": "[Histochemical and histological investigations on the vagina of the beagle she-dog during various functional conditions (author's transl)]. Histotopochemistry and histology of vaginal epithelium in female beagles were studied during oestrus, metoestrus-dioestrus, post partum period and at days 20, 30, 40, 50, 60 of pregnancy. During oestrus the epithelium is uniform throughout the whole vagina: it presents itself as a high, uncornified, stratified squamous epithelium with some glycogen and lipid droplets but devoid of leucocytes. The intercellular gaps of the stratum intermedium give strong reactions for ATPase and alkaline phosphatase. The activities of oxidoreductases studied decrease continuously from basal to apical. During gravidity, post partum period and metoestrus-dioestrus distinct morphological and histochemical differences can be stated between the cranial and caudal vaginal portions. Caudal vaginal epithelium outside oestrus remains of stratified squamous type. It exhibits strong mucification during pregnancy. The PAS-positive mucous substances prefer a position in the enlarged intercellular gaps of stratum intermedium and superficiale. During pregnancy the epithelium is relatively rich in acid and completely devoid of alkaline phosphatases. Outside oestrus the epithelium of the cranial vaginal region is a relatively flat, stratified columnar one and contains leucocytes with regularity. Also the cranial vaginal portion undergoes mucification during pregnancy with a maximum about day 33. The mucous material is situated intracellularly and not within the intercellular gaps. Further, larger intraepithelial mucus cysts are observed. Alkaline phosphatase is found during gravidity in the basal region and an adluminal border of the epithelium. The reactions for oxidoreductases are strongest in the columnar cell layer which shows more functional adaptations than the remainder of the epithelium. Histochemical tests for beta-D-glucuronidase and leucine aminopeptidase give negative results in the whole vagina during all different functional stages studied."} {"id": "PMID:171904", "title": "Histochemical study of metrial gland cells through the last week of pregnancy in the albino rat.", "content": "The metrial gland cells of the rat were studied from day 16 to 21 of pregnancy through enzyme histochemistry. The following enzyme activities were tested: 2 carboxylic esterases, 4 phosphatases, 1 aminopeptidase and 10 dehydrogenases including 4 which are involved in steroid metabolism. Although acid phosphatase activity was strong in mesenchymal cells, it remained undetected in large, sometimes binucleate cells lining central and subplacental vessels of the mesometrial triangle. 5-Bromo-indoxyl acetate esterase was likewise absent from the parietal vascular cells of the central artery. The study of 6 enzyme activities, i.e., GPDH, 3-OU-BDH, G6PDH, 3-B-HSDH, primary and secondary alcohol dehydrogenases, allowed to conclude that metrial gland cells are actively involved in steroidogenesis and lipid catabolism. Maternal origin of this gland can be sustained with reference to the pattern of acid phosphatase, indoxyl-esterase and some oxidoreductases II activities distribution which appears to be different from what is found in the trophospongium area.", "contents": "Histochemical study of metrial gland cells through the last week of pregnancy in the albino rat. The metrial gland cells of the rat were studied from day 16 to 21 of pregnancy through enzyme histochemistry. The following enzyme activities were tested: 2 carboxylic esterases, 4 phosphatases, 1 aminopeptidase and 10 dehydrogenases including 4 which are involved in steroid metabolism. Although acid phosphatase activity was strong in mesenchymal cells, it remained undetected in large, sometimes binucleate cells lining central and subplacental vessels of the mesometrial triangle. 5-Bromo-indoxyl acetate esterase was likewise absent from the parietal vascular cells of the central artery. The study of 6 enzyme activities, i.e., GPDH, 3-OU-BDH, G6PDH, 3-B-HSDH, primary and secondary alcohol dehydrogenases, allowed to conclude that metrial gland cells are actively involved in steroidogenesis and lipid catabolism. Maternal origin of this gland can be sustained with reference to the pattern of acid phosphatase, indoxyl-esterase and some oxidoreductases II activities distribution which appears to be different from what is found in the trophospongium area."} {"id": "PMID:171905", "title": "The effect of ACTH and cortisone on the carbohydrate-protein complexes of different types of epithelium in relation to their embryological origin.", "content": "Using histochemical methods the authors studied the effect of ACTH and cortisone on carbohydrate-protein complexes of epithelial cells derived from 3 different germ layers. It has been shown that cortisone increased the intensity of PAS reaction in all types of the epithelium investigated. Changes in acid mucosubstances after treatment with cortisone were different. After the administration of ACTH the observed changes in epithelium were not parallel to the changes seen after treatment with cortisone.", "contents": "The effect of ACTH and cortisone on the carbohydrate-protein complexes of different types of epithelium in relation to their embryological origin. Using histochemical methods the authors studied the effect of ACTH and cortisone on carbohydrate-protein complexes of epithelial cells derived from 3 different germ layers. It has been shown that cortisone increased the intensity of PAS reaction in all types of the epithelium investigated. Changes in acid mucosubstances after treatment with cortisone were different. After the administration of ACTH the observed changes in epithelium were not parallel to the changes seen after treatment with cortisone."} {"id": "PMID:171906", "title": "[In vitro evaluation of antiviral inhibitors by means of a turbidity method (author's transl)].", "content": "The paper presents a photometric method for the determination of virus-induced alterations (cytopathogenic effects) of cells based on nephelometric analysis. These were taken at varying time intervals after infection and with different multiplicity of infection. It was demonstrated that suppression of virus-induced CPE by the known inhibitors could also be followed by turbidity measurements. The in vitro experiments were carried out in the 2 following virus-cell-systems: Pseudorabies virus in chick-embryo cells and Mengo virus in FL-cells, respectively. According to these studies the measurements were extended to other virus strains and inhibitors (antibiotics, chemicals, and antimetabolites). The results obtained confirm the applicability of the photometric method for the screening of antiviral drugs.", "contents": "[In vitro evaluation of antiviral inhibitors by means of a turbidity method (author's transl)]. The paper presents a photometric method for the determination of virus-induced alterations (cytopathogenic effects) of cells based on nephelometric analysis. These were taken at varying time intervals after infection and with different multiplicity of infection. It was demonstrated that suppression of virus-induced CPE by the known inhibitors could also be followed by turbidity measurements. The in vitro experiments were carried out in the 2 following virus-cell-systems: Pseudorabies virus in chick-embryo cells and Mengo virus in FL-cells, respectively. According to these studies the measurements were extended to other virus strains and inhibitors (antibiotics, chemicals, and antimetabolites). The results obtained confirm the applicability of the photometric method for the screening of antiviral drugs."} {"id": "PMID:171907", "title": "Enzyme histochemistry of undecalcified bone and cartilage embedded in glycol methacrylate.", "content": "Undecalcified bone and cartilage tissue blocks were fixed for 3 h in cold formol-calcium, rapidly dehydrated with a graded series of cold ethanol, and embedded in glycol methacrylate. 2 mum sections were produced with a Sorvall JB-4 microtome using glass knives. The quality of the sections were usually excellent except for hard bone from old subjects where the bone sometimes shattered while sectioning. This method is short, relatively uninvolved and eliminates en bloc decalcification. Moreover, the method is gentle enough to allow the histochemical demonstration of alkaline and acid phosphatase by the azo dye methods, and acid phosphatase, 5'-nucleotidase and ATPase by the lead precipitation methods.", "contents": "Enzyme histochemistry of undecalcified bone and cartilage embedded in glycol methacrylate. Undecalcified bone and cartilage tissue blocks were fixed for 3 h in cold formol-calcium, rapidly dehydrated with a graded series of cold ethanol, and embedded in glycol methacrylate. 2 mum sections were produced with a Sorvall JB-4 microtome using glass knives. The quality of the sections were usually excellent except for hard bone from old subjects where the bone sometimes shattered while sectioning. This method is short, relatively uninvolved and eliminates en bloc decalcification. Moreover, the method is gentle enough to allow the histochemical demonstration of alkaline and acid phosphatase by the azo dye methods, and acid phosphatase, 5'-nucleotidase and ATPase by the lead precipitation methods."} {"id": "PMID:171908", "title": "Renal transplantation in children.", "content": "From July 1967 to September 1974, 26 kidney transplantations were carried out in 16 children aged 6 to 17 years, in Gotherburg. The average age at the primary transplantation was 12 years and average body weight 29.7 kg. Five patients had familial juvenile nephronophthisis, 5 chronic glomerulonephritis, 5 chronic pyelonephritis, and one bilateral Wilms's tumour. Four patients were predialytic. Fourteen grafts came from living related donors. The surgical technique was standard as was the immunosuppression with azathioprine and cortisone; exceptionally antilymphocyte globulin was used. Thirteen patients were alive in September 1974, observed 2-65 months, 8 with a normal serum creatinine, 3 with moderately elevated serum creatinine, and 2 on hemodialysis. The 6- and 12-month survivals of patients are 100% and 93% respectively. Normal growth and full rehabilitation in recipients of functioning grafts make renal transplantation justified as a therapeutic procedure in terminally uremic children.", "contents": "Renal transplantation in children. From July 1967 to September 1974, 26 kidney transplantations were carried out in 16 children aged 6 to 17 years, in Gotherburg. The average age at the primary transplantation was 12 years and average body weight 29.7 kg. Five patients had familial juvenile nephronophthisis, 5 chronic glomerulonephritis, 5 chronic pyelonephritis, and one bilateral Wilms's tumour. Four patients were predialytic. Fourteen grafts came from living related donors. The surgical technique was standard as was the immunosuppression with azathioprine and cortisone; exceptionally antilymphocyte globulin was used. Thirteen patients were alive in September 1974, observed 2-65 months, 8 with a normal serum creatinine, 3 with moderately elevated serum creatinine, and 2 on hemodialysis. The 6- and 12-month survivals of patients are 100% and 93% respectively. Normal growth and full rehabilitation in recipients of functioning grafts make renal transplantation justified as a therapeutic procedure in terminally uremic children."} {"id": "PMID:171909", "title": "The long-term effects of protein energy malnutrition in early childhood on bone age, bone cortical thickness and height.", "content": "Three groups of Ugandan children, 18 in each group, and one comparison group of 18 children were examined at 11-17 years of age. The three groups had previously been admitted for treatment of protein energy malnutrition between the ages of 8 to 15, 16 to 21 and 22 to 27 months respectively. The comparison group had not been clinically malnourished throughout the period up to 27 months of age. The children came from one tribe and from similar socio-economic background, and were individually matched on age and sex. The bone age was estimated by hand wrist radiography scored for maturity by the Tanner & Whitehouse method. The metacarpal index, a ratio derived from the medullary width and full diameter of the mid-point of the second metacarpal, was used as a measure of bone cortical thickness. The three malnourished groups are significantly shorter in height than the comparison group, but are not different in bone age and metacarpal index. No differences are observed between the three groups of children who had been admitted for protein energy malnutrition at different ages. The findings are discussed as they relate to the existing literature.", "contents": "The long-term effects of protein energy malnutrition in early childhood on bone age, bone cortical thickness and height. Three groups of Ugandan children, 18 in each group, and one comparison group of 18 children were examined at 11-17 years of age. The three groups had previously been admitted for treatment of protein energy malnutrition between the ages of 8 to 15, 16 to 21 and 22 to 27 months respectively. The comparison group had not been clinically malnourished throughout the period up to 27 months of age. The children came from one tribe and from similar socio-economic background, and were individually matched on age and sex. The bone age was estimated by hand wrist radiography scored for maturity by the Tanner & Whitehouse method. The metacarpal index, a ratio derived from the medullary width and full diameter of the mid-point of the second metacarpal, was used as a measure of bone cortical thickness. The three malnourished groups are significantly shorter in height than the comparison group, but are not different in bone age and metacarpal index. No differences are observed between the three groups of children who had been admitted for protein energy malnutrition at different ages. The findings are discussed as they relate to the existing literature."} {"id": "PMID:171910", "title": "Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver.", "content": "Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malm\u00f6 were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis.", "contents": "Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver. Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malm\u00f6 were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis."} {"id": "PMID:171911", "title": "The effect of angiotensin infusion, sodium loading and sodium restriction on the renal and cardiac adrenergic nerves.", "content": "The renal and cardiac adrenergic nerve patterns in rats infused with large and small amounts of angiotensin and in rats given NaCl plus DOCA, NaCl alone, and salt-free diets were examined by the histochemical fluorescence method. Infusion of small amounts of angiotensin led to a persistent blood pressure elevation whereas infusion of large amounts of angiotensin resulted in a transient rise in blood pressure, probably due to the development of tachyphylaxis. Nerve patterns were found to be normal in angiotensin-infused rats and in rats given NaCl. In rats given NaCl plus DOCA and in rats subjected to salt restriction, a partial or complete disappearance of the transmitter of the adrenergic nerve terminals were recorded. The findings suggest that angiotensin in itself is incapable of inducing visible alterations in the transmitter content of the terminals. The findings agree with the view that angiotensin potentiates a norepinephrine depletion of the terminals during sympathetic activity, since it can be assumed that increased plasma angiotensin levels as well as various degrees of increased sympathetic tonus were present in the rats subjected to salt restriction. The similar effect on the nerve terminals produced by the combined NaCl and DOCA administration is consistent with earlier reports of an increased turnover of norepinephrine in animals thus treated.", "contents": "The effect of angiotensin infusion, sodium loading and sodium restriction on the renal and cardiac adrenergic nerves. The renal and cardiac adrenergic nerve patterns in rats infused with large and small amounts of angiotensin and in rats given NaCl plus DOCA, NaCl alone, and salt-free diets were examined by the histochemical fluorescence method. Infusion of small amounts of angiotensin led to a persistent blood pressure elevation whereas infusion of large amounts of angiotensin resulted in a transient rise in blood pressure, probably due to the development of tachyphylaxis. Nerve patterns were found to be normal in angiotensin-infused rats and in rats given NaCl. In rats given NaCl plus DOCA and in rats subjected to salt restriction, a partial or complete disappearance of the transmitter of the adrenergic nerve terminals were recorded. The findings suggest that angiotensin in itself is incapable of inducing visible alterations in the transmitter content of the terminals. The findings agree with the view that angiotensin potentiates a norepinephrine depletion of the terminals during sympathetic activity, since it can be assumed that increased plasma angiotensin levels as well as various degrees of increased sympathetic tonus were present in the rats subjected to salt restriction. The similar effect on the nerve terminals produced by the combined NaCl and DOCA administration is consistent with earlier reports of an increased turnover of norepinephrine in animals thus treated."} {"id": "PMID:171912", "title": "Histology of the human corpus luteum of early and late pregnancy.", "content": "The aim of this investigation has been to examine which histological parameters are of value in the age determination of the corpus luteum of pregnancy. The material comprises representative ovarian biopsies from 16 women from the 10th through 42nd week of gestation. The following histological parameters have been found useful for the age determination of the corpus luteum: 1) the size of the granulosa cells; 2) the number of K-cells, vacuoles and colloid inclusions in the granulosa cell layer; 3) the size of the theca interna cells; (4) the size of the vessels in the theca interna. Futhermore, the differentiation of the corpus luteum of pregnancy from the corpus luteum of menstruation is described, and some indications for a histological age determination of the corpus luteum of pregnancy are mentioned.", "contents": "Histology of the human corpus luteum of early and late pregnancy. The aim of this investigation has been to examine which histological parameters are of value in the age determination of the corpus luteum of pregnancy. The material comprises representative ovarian biopsies from 16 women from the 10th through 42nd week of gestation. The following histological parameters have been found useful for the age determination of the corpus luteum: 1) the size of the granulosa cells; 2) the number of K-cells, vacuoles and colloid inclusions in the granulosa cell layer; 3) the size of the theca interna cells; (4) the size of the vessels in the theca interna. Futhermore, the differentiation of the corpus luteum of pregnancy from the corpus luteum of menstruation is described, and some indications for a histological age determination of the corpus luteum of pregnancy are mentioned."} {"id": "PMID:171913", "title": "Different effects on renal and submaxillary renin release after blockade of the renin system in mice.", "content": "Ingibition of the angiotensin I converting enzyme with SQ 20,881 results in a rapid marked increase in plasma renin concentration in mice. The maximum effect is short-lasting, but the values are still elevated 2 hours after the injection, the time course being similar to that previously found in rats. The relative increase is the same in normal and sialo-adenectomized mice. The plasma renin concentration of nephrectomized mice with their submaxillary glands intact is, however, totally uninfluenced by injection of the blocker. This finding indicates that renin release from the submaxillary glands is not controlled by the plasma angiotensin II concentration as is that of the renin release from the kidneys.", "contents": "Different effects on renal and submaxillary renin release after blockade of the renin system in mice. Ingibition of the angiotensin I converting enzyme with SQ 20,881 results in a rapid marked increase in plasma renin concentration in mice. The maximum effect is short-lasting, but the values are still elevated 2 hours after the injection, the time course being similar to that previously found in rats. The relative increase is the same in normal and sialo-adenectomized mice. The plasma renin concentration of nephrectomized mice with their submaxillary glands intact is, however, totally uninfluenced by injection of the blocker. This finding indicates that renin release from the submaxillary glands is not controlled by the plasma angiotensin II concentration as is that of the renin release from the kidneys."} {"id": "PMID:171916", "title": "Studies of some twitch and fatigue properties of different motor unit types in the ankle muscles of the adult cat.", "content": "Contractile responses of motor units in the gastrocnemius, soleus and pretibial flexor muscles of adult cats were elicited by intracellular stimulation of motoneurones. The motor units were classified into types FF, FR and S (Burke et al. 1971) and their responses to the same stimulation patterns as those used in a previous investigation of whole muscles (Hammarberg and Kellerth 1975 a) were studied. The duration of motoneurone afterhyperpolarization was short in both the fast twitch FF and FR units; it was longer in the soleus S units than in the S units of the pale muscles. Twitch time-to-peak was less than 30 ms in the FF and FR units, but exceeded 40 ms in the S units. Soleus S units were slower than S units of the pale muscles. Potentiation was observed in the gastrocnemius units, but not in the soleus S units. A short rest allowed fatigued extensor units of the FF and FR types to regain some contractile strength. This was less evident in the S units which, on the other hand, were extremely resistant to fatigue. Differences in response patterns between corresponding motor unit types of the flexor and extensor muscles were observed. A few fast twitch units were identified in the slow soleus muscle.", "contents": "Studies of some twitch and fatigue properties of different motor unit types in the ankle muscles of the adult cat. Contractile responses of motor units in the gastrocnemius, soleus and pretibial flexor muscles of adult cats were elicited by intracellular stimulation of motoneurones. The motor units were classified into types FF, FR and S (Burke et al. 1971) and their responses to the same stimulation patterns as those used in a previous investigation of whole muscles (Hammarberg and Kellerth 1975 a) were studied. The duration of motoneurone afterhyperpolarization was short in both the fast twitch FF and FR units; it was longer in the soleus S units than in the S units of the pale muscles. Twitch time-to-peak was less than 30 ms in the FF and FR units, but exceeded 40 ms in the S units. Soleus S units were slower than S units of the pale muscles. Potentiation was observed in the gastrocnemius units, but not in the soleus S units. A short rest allowed fatigued extensor units of the FF and FR types to regain some contractile strength. This was less evident in the S units which, on the other hand, were extremely resistant to fatigue. Differences in response patterns between corresponding motor unit types of the flexor and extensor muscles were observed. A few fast twitch units were identified in the slow soleus muscle."} {"id": "PMID:171917", "title": "Liver, lung and malignant disease in heterozygous (Pi MZ) alpha1-antitrypsin deficiency.", "content": "Theoccurrence of PAS-positive, diastase-resistant, inclusion bodies in hepatocytes has been used as a marker of heterozygous (Pi MZ) alpha1-antitrypsin deficiency in order to study the frequency of lung, liver and malignant disease in a consecutive autopsy material from a well defined population. Typical PAS-positive inclusion bodies were found in the liver in 26 (3.7%) of the 700 cases studied. In these 26 subjects both liver (cirrhosis or fibrosis) and lung disease (emphysema) were significantly more prevalent (p less than 0.001) than among PAS-negative controls. The prevalence of malignant disease did not differ between the groups. The results are consistent with the concept that heterozygous (Pi MZ) alpha1-antitrypsin deficiency predisposes to both liver and lung disease but does not influence the survival rate.", "contents": "Liver, lung and malignant disease in heterozygous (Pi MZ) alpha1-antitrypsin deficiency. Theoccurrence of PAS-positive, diastase-resistant, inclusion bodies in hepatocytes has been used as a marker of heterozygous (Pi MZ) alpha1-antitrypsin deficiency in order to study the frequency of lung, liver and malignant disease in a consecutive autopsy material from a well defined population. Typical PAS-positive inclusion bodies were found in the liver in 26 (3.7%) of the 700 cases studied. In these 26 subjects both liver (cirrhosis or fibrosis) and lung disease (emphysema) were significantly more prevalent (p less than 0.001) than among PAS-negative controls. The prevalence of malignant disease did not differ between the groups. The results are consistent with the concept that heterozygous (Pi MZ) alpha1-antitrypsin deficiency predisposes to both liver and lung disease but does not influence the survival rate."} {"id": "PMID:171918", "title": "Lp(alpha) lipoprotein and pre-beta1-lipoprotein in relation to lipid levels in males.", "content": "Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein.", "contents": "Lp(alpha) lipoprotein and pre-beta1-lipoprotein in relation to lipid levels in males. Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein."} {"id": "PMID:171919", "title": "A rapid screening test for Cushing's syndrome.", "content": "A combination test consisting of two parts, a single dose of dexamethasone and a (1-24) ACTH injection, has been used for the diagnosis of Cushing's syndrome. The test was performed by administering 1 mg dexamethasone orally at 11 p.m. on the first day and 25 IU synthetic ACTH i.v. at 8 a.m. on the second day. Plasma cortisol was determined at 8 a.m. on the first and second day and 1-1/2 and 2 hours after the ACTH injection. The test was performed in 33 patients with Cushing's syndrome and in 114 controls without adrenal disease. After dexamethasone administration alone, cortisol values frequently overlapped between patients with Cushing's syndrome and controls. The validity of the test was considerably improved by adding ACTH stimulation. The test procedure is recommended as a screening test for Cushing's syndrome in ambulatory practice.", "contents": "A rapid screening test for Cushing's syndrome. A combination test consisting of two parts, a single dose of dexamethasone and a (1-24) ACTH injection, has been used for the diagnosis of Cushing's syndrome. The test was performed by administering 1 mg dexamethasone orally at 11 p.m. on the first day and 25 IU synthetic ACTH i.v. at 8 a.m. on the second day. Plasma cortisol was determined at 8 a.m. on the first and second day and 1-1/2 and 2 hours after the ACTH injection. The test was performed in 33 patients with Cushing's syndrome and in 114 controls without adrenal disease. After dexamethasone administration alone, cortisol values frequently overlapped between patients with Cushing's syndrome and controls. The validity of the test was considerably improved by adding ACTH stimulation. The test procedure is recommended as a screening test for Cushing's syndrome in ambulatory practice."} {"id": "PMID:171920", "title": "Effects of electrical stimulation of the mesencephalon and diencephalon on the paradoxical phase of sleep.", "content": "During paradoxical sleep electrical stimulation of the mesencephalic reticular formation and emotiogenic structures in the mesencephalon and diencephalon produced depression or an increase in the theta rhythm of the hippocampal and entorhinal electrical activity. However, stimulation not involving behavioral arousal did not cause a transition from paradoxical phase into slow wave sleep. The cessation of stimulation restored the normal structure of the paradoxical phase. Stimulation of the reticular formation causing the depression of the hippocampal and entorhinal theta rhythm without behavioral arousal did not affect duration of the paradoxical phase, which was shortened, however, by electrical stimulation of the emotiogenic structures evoking an increase in the hippocampal and entorhinal theta rhythms. Stimulation of ventromedial hypothalamus or septum (during wakefulness inhibiting motivational behavior and emotional stress) caused transition from the paradoxical into slow wave sleep. This is probably caused by a decrease in emotiogenic stress, which during the paradoxical phase is usually on a high level.", "contents": "Effects of electrical stimulation of the mesencephalon and diencephalon on the paradoxical phase of sleep. During paradoxical sleep electrical stimulation of the mesencephalic reticular formation and emotiogenic structures in the mesencephalon and diencephalon produced depression or an increase in the theta rhythm of the hippocampal and entorhinal electrical activity. However, stimulation not involving behavioral arousal did not cause a transition from paradoxical phase into slow wave sleep. The cessation of stimulation restored the normal structure of the paradoxical phase. Stimulation of the reticular formation causing the depression of the hippocampal and entorhinal theta rhythm without behavioral arousal did not affect duration of the paradoxical phase, which was shortened, however, by electrical stimulation of the emotiogenic structures evoking an increase in the hippocampal and entorhinal theta rhythms. Stimulation of ventromedial hypothalamus or septum (during wakefulness inhibiting motivational behavior and emotional stress) caused transition from the paradoxical into slow wave sleep. This is probably caused by a decrease in emotiogenic stress, which during the paradoxical phase is usually on a high level."} {"id": "PMID:171938", "title": "Coronary insufficiency in children. Coronary arteriographic studies in two siblings from a family with hyperbetalipoproteinemia.", "content": "A family affected with hyperbetalipoproteinemia was studied. Two siblings, a boy 11 and a girl 9 years of age, with characteristic findings of homozygous type II hyperlipoproteinemia are described. The highly atherogenetic nature of this disorder is illustrated by the occurrence of progressive coronary atheromatosis in the boy, in whom two coronary arteriographic studies documented the development of progressive obstruction of two coronary arteries in the course of 2 years. During this interval angina pectoris developed followed by myocardial infarction, cardiomegaly and congestive heart failure. The sister has remained asymptomatic, with apparently normal coronary arteries at age 9 years. Phonocardiograms were suggestive of aortic valve involvement although no aortic valve gradient was demonstrated by cardiac catheterization.", "contents": "Coronary insufficiency in children. Coronary arteriographic studies in two siblings from a family with hyperbetalipoproteinemia. A family affected with hyperbetalipoproteinemia was studied. Two siblings, a boy 11 and a girl 9 years of age, with characteristic findings of homozygous type II hyperlipoproteinemia are described. The highly atherogenetic nature of this disorder is illustrated by the occurrence of progressive coronary atheromatosis in the boy, in whom two coronary arteriographic studies documented the development of progressive obstruction of two coronary arteries in the course of 2 years. During this interval angina pectoris developed followed by myocardial infarction, cardiomegaly and congestive heart failure. The sister has remained asymptomatic, with apparently normal coronary arteries at age 9 years. Phonocardiograms were suggestive of aortic valve involvement although no aortic valve gradient was demonstrated by cardiac catheterization."} {"id": "PMID:171939", "title": "Autonomic nervous cardiovascular regulation in borderline hypertension.", "content": "Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension.", "contents": "Autonomic nervous cardiovascular regulation in borderline hypertension. Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension."} {"id": "PMID:171940", "title": "Application of adrenocorticotropin assays in a routine clinical laboratory.", "content": "The radioimmunoassay of ACTH was used in a routine laboratory to localize the site of the lesion in 20 patients with Cushing's syndrome. Eight of the patients had no detectable circulating ACTH and had adrenal tumors removed, 12 had high levels and were diagnosed as having pituitary Cushing's syndrome. Very high levels of plasma ACTH were found in eight patients who had primary adrenal insufficiency, while ACTH was undetectable in ten patients with secondary hypoadrenalism. The routine use of this assay in endocrinology should reduce the hospitalization of patients under investigation for disorders of the pituitary--adrenal axis. Eight patients who had the ectopic ACTH syndrome and carcinoma of the lung were found to have very high levels of ACTH with no diurnal variation. Forty-seven patients with oat-cell carcinoma but without evidence of the ectopic ACTH syndrome had normal ACTH levels. A possible role of ACTH and other peptide hormones as tumor markers is mentioned.", "contents": "Application of adrenocorticotropin assays in a routine clinical laboratory. The radioimmunoassay of ACTH was used in a routine laboratory to localize the site of the lesion in 20 patients with Cushing's syndrome. Eight of the patients had no detectable circulating ACTH and had adrenal tumors removed, 12 had high levels and were diagnosed as having pituitary Cushing's syndrome. Very high levels of plasma ACTH were found in eight patients who had primary adrenal insufficiency, while ACTH was undetectable in ten patients with secondary hypoadrenalism. The routine use of this assay in endocrinology should reduce the hospitalization of patients under investigation for disorders of the pituitary--adrenal axis. Eight patients who had the ectopic ACTH syndrome and carcinoma of the lung were found to have very high levels of ACTH with no diurnal variation. Forty-seven patients with oat-cell carcinoma but without evidence of the ectopic ACTH syndrome had normal ACTH levels. A possible role of ACTH and other peptide hormones as tumor markers is mentioned."} {"id": "PMID:171941", "title": "Hemiatrophy and hemiparesis in a patient with congenital cytomegalovirus infection.", "content": "A 3-year-old girl with congenital cytomegalovirus (CMV) infection has been followed up since birth. Hemiatrophy and hemiparesis occurred at 9 months of age. These unusual sequels of congenital CMV infection should encourage physicians to do longitudinal studies on infants with congenital CMV infection, as well as to examine children with hemiatrophy and hemiparesis for CMV infection.", "contents": "Hemiatrophy and hemiparesis in a patient with congenital cytomegalovirus infection. A 3-year-old girl with congenital cytomegalovirus (CMV) infection has been followed up since birth. Hemiatrophy and hemiparesis occurred at 9 months of age. These unusual sequels of congenital CMV infection should encourage physicians to do longitudinal studies on infants with congenital CMV infection, as well as to examine children with hemiatrophy and hemiparesis for CMV infection."} {"id": "PMID:171942", "title": "Pseudohypoparathyroidism with normal serum calcium level.", "content": "A mildly obese 15-year-old boy had short stature with rounded facies and short, stubby hands and toes. He had the fully expressed syndrome of pseudohypoparathyroidism but was the only member of his family who had all the somatic characteristics of this disease. The serum parathyroid hormone level was substantially elevated. Urinary excretion of cyclic adenosine monophosphate and phosphate failed to increase following intravenous infusion of parathyroid hormone. However, he did not have hypocalcemia. The present entity is probably a transient form of pseudohypoparathyroidism with partial responsiveness of skeletal adenyl cyclase to parathyroid hormone.", "contents": "Pseudohypoparathyroidism with normal serum calcium level. A mildly obese 15-year-old boy had short stature with rounded facies and short, stubby hands and toes. He had the fully expressed syndrome of pseudohypoparathyroidism but was the only member of his family who had all the somatic characteristics of this disease. The serum parathyroid hormone level was substantially elevated. Urinary excretion of cyclic adenosine monophosphate and phosphate failed to increase following intravenous infusion of parathyroid hormone. However, he did not have hypocalcemia. The present entity is probably a transient form of pseudohypoparathyroidism with partial responsiveness of skeletal adenyl cyclase to parathyroid hormone."} {"id": "PMID:171946", "title": "Joint effusions, chondrocalcinosis and other rheumatic manifestations in hypothyroidism. A clinicopathologic study.", "content": "Twelve patients with severe hypothyroidism and rheumatic signs and symptoms were studied before or within four days of receiving thyroid replacement therapy. Eight patients had synovial effusions. Seven effusions were extremely viscous and six contained calcium pyrophosphate crystals. Leukocyte counts were less than 1,000/mm3, except in two patients during crystal-induced synovitis. \"Bulge signs\" were present but often sluggish, possibly because of the viscosity of the fluid. Flexor tendon sheath thickening, joint laxity and popliteal cysts were documented. All patients complained of generalized stiffness and two had proximal myopathy. Roentgenograms were obtained in 11 patients, and chondrocalcinosis was identified in seven. Needle synovial biopsy specimens in five patients showed only mild inflammation in the thick synovium. These findings can suggest hypothyroidism, a treatable disease, as the cause of musculoskeletal problems.", "contents": "Joint effusions, chondrocalcinosis and other rheumatic manifestations in hypothyroidism. A clinicopathologic study. Twelve patients with severe hypothyroidism and rheumatic signs and symptoms were studied before or within four days of receiving thyroid replacement therapy. Eight patients had synovial effusions. Seven effusions were extremely viscous and six contained calcium pyrophosphate crystals. Leukocyte counts were less than 1,000/mm3, except in two patients during crystal-induced synovitis. \"Bulge signs\" were present but often sluggish, possibly because of the viscosity of the fluid. Flexor tendon sheath thickening, joint laxity and popliteal cysts were documented. All patients complained of generalized stiffness and two had proximal myopathy. Roentgenograms were obtained in 11 patients, and chondrocalcinosis was identified in seven. Needle synovial biopsy specimens in five patients showed only mild inflammation in the thick synovium. These findings can suggest hypothyroidism, a treatable disease, as the cause of musculoskeletal problems."} {"id": "PMID:171947", "title": "Necrotizing pneumonia and empyema due to Clostridium perfringens. Report of a case and review of the literature.", "content": "Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection.", "contents": "Necrotizing pneumonia and empyema due to Clostridium perfringens. Report of a case and review of the literature. Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection."} {"id": "PMID:171948", "title": "Atypical adrenal insufficiency with failure of the pituitary feedback receptor. A case with associated diabetes mellitus and selective IgA deficiency with steatorrhea.", "content": "A 59 year old woman with insulin-dependent diabetes mellitus and chronic diarrhea was found to have mild steatorrhea, selective plasma IgA deficiency and adrenal insufficiency. Significant adrenal secretion of corticosteroids resulted only after prolonged stimulation with large doses of exogenous ACTH. Plasma ACTH levels were not elevated during clinical adrenal insufficiency or after metyrapone administration but did respond normally to vasopressin and insulin-induced hypoglycemia. These studies were interpreted as showing both primary adrenal insufficiency and impaired pituitary reserve for ACTH secretion in response to the feedback stimulus. No deficiency was found in secretion of other pituitary tropic hormones. Jejunal biopsy showed a lack of IgA-containing plasma cells. With cortisone replacement, diarrhea subsided and a malabsorption pattern on a film of the small bowel was no longer seen. IgA deficiency has been noted frequently with steatorrhea but rarely with diabetes and only once previously with adrenal insufficiency.", "contents": "Atypical adrenal insufficiency with failure of the pituitary feedback receptor. A case with associated diabetes mellitus and selective IgA deficiency with steatorrhea. A 59 year old woman with insulin-dependent diabetes mellitus and chronic diarrhea was found to have mild steatorrhea, selective plasma IgA deficiency and adrenal insufficiency. Significant adrenal secretion of corticosteroids resulted only after prolonged stimulation with large doses of exogenous ACTH. Plasma ACTH levels were not elevated during clinical adrenal insufficiency or after metyrapone administration but did respond normally to vasopressin and insulin-induced hypoglycemia. These studies were interpreted as showing both primary adrenal insufficiency and impaired pituitary reserve for ACTH secretion in response to the feedback stimulus. No deficiency was found in secretion of other pituitary tropic hormones. Jejunal biopsy showed a lack of IgA-containing plasma cells. With cortisone replacement, diarrhea subsided and a malabsorption pattern on a film of the small bowel was no longer seen. IgA deficiency has been noted frequently with steatorrhea but rarely with diabetes and only once previously with adrenal insufficiency."} {"id": "PMID:171949", "title": "Viral hepatitis: a pathologic spectrum.", "content": "Acute viral hepatitis has several identifiable morphologic components but the major categories are (1) cytopathic, (2) inflammatory, and (3) regenerative. Each category has independently variable characteristics. Extreme alterations related to severity of disease, alteration of immune response, or pre-existing liver disease may result in diagnostic difficulties for the pathologist. In contrast to the usual concept, patients who survive fulminant viral hepatitis rarely, if ever, develop cirrhosis and those who have severe hepatic necrosis from hepatitis also do not usually develop serious sequelae of that disease except in the older age group where the difficulty is in impaired regeneration (IR). The usual criteria for the diagnosis of chronic active hepatitis or chronic aggressive hepatitis need a thorough review since many of the variations of acute viral hepatitis result in histologic patterns that might be considered to be chronic aggressive hepatitis using the previous definitions; yet such patients recover without developing chronic liver disease. Chronic active hepatitis, a progressive hepatic disorder, is characterized by changes in the distribution of necrosis and regeneration within the lobule from that usually observed in acute viral hepatitis. Persistent viral hepatitis, a development in 10 to 12 per cent of adult patients after icteric acute disease, is characterized by a \"cobblestone\" hepatocellular change that resembles continued regeneration, focal hepatocytolysis, and often portal lymphoid hyperplasia. Apparently with time, these histologic features fade and the incidence, in type B PVH, of \"ground glass\" HBs Ag laden cells increases. This may reflect a continued adaptation of host and virus to one another.", "contents": "Viral hepatitis: a pathologic spectrum. Acute viral hepatitis has several identifiable morphologic components but the major categories are (1) cytopathic, (2) inflammatory, and (3) regenerative. Each category has independently variable characteristics. Extreme alterations related to severity of disease, alteration of immune response, or pre-existing liver disease may result in diagnostic difficulties for the pathologist. In contrast to the usual concept, patients who survive fulminant viral hepatitis rarely, if ever, develop cirrhosis and those who have severe hepatic necrosis from hepatitis also do not usually develop serious sequelae of that disease except in the older age group where the difficulty is in impaired regeneration (IR). The usual criteria for the diagnosis of chronic active hepatitis or chronic aggressive hepatitis need a thorough review since many of the variations of acute viral hepatitis result in histologic patterns that might be considered to be chronic aggressive hepatitis using the previous definitions; yet such patients recover without developing chronic liver disease. Chronic active hepatitis, a progressive hepatic disorder, is characterized by changes in the distribution of necrosis and regeneration within the lobule from that usually observed in acute viral hepatitis. Persistent viral hepatitis, a development in 10 to 12 per cent of adult patients after icteric acute disease, is characterized by a \"cobblestone\" hepatocellular change that resembles continued regeneration, focal hepatocytolysis, and often portal lymphoid hyperplasia. Apparently with time, these histologic features fade and the incidence, in type B PVH, of \"ground glass\" HBs Ag laden cells increases. This may reflect a continued adaptation of host and virus to one another."} {"id": "PMID:171951", "title": "Persistent HB antigenemia: associated clinical manifestations and hepatic lesions.", "content": "The clinical, biochemical and histological features in nine asymptomatic HBs Ag carriers, 15 patients with symptomatic HBs Ag-positive chronic active hepatitis (CAH), and 29 patients with HBs antigenemia persistent for five months or longer following a documented attack of acute viral hepatitis were compared, and contrasted with those in 67 patients with HBs Ag-negative CAH. The findings were remarkably similar in all groups. However, young males predominated in all three HBs Ag-positive groups, whereas most HBs Ag-negative cases of CAH were in middle-aged women. Moreover, in the latter group, the lesions tended to be more extensive and more commonly were accompanied by smooth muscle antibody, antinuclear antibody and LE cells, and extrahepatic manifestations, such as ulcerative colitis, arthritis, pleurisy and pericarditis.", "contents": "Persistent HB antigenemia: associated clinical manifestations and hepatic lesions. The clinical, biochemical and histological features in nine asymptomatic HBs Ag carriers, 15 patients with symptomatic HBs Ag-positive chronic active hepatitis (CAH), and 29 patients with HBs antigenemia persistent for five months or longer following a documented attack of acute viral hepatitis were compared, and contrasted with those in 67 patients with HBs Ag-negative CAH. The findings were remarkably similar in all groups. However, young males predominated in all three HBs Ag-positive groups, whereas most HBs Ag-negative cases of CAH were in middle-aged women. Moreover, in the latter group, the lesions tended to be more extensive and more commonly were accompanied by smooth muscle antibody, antinuclear antibody and LE cells, and extrahepatic manifestations, such as ulcerative colitis, arthritis, pleurisy and pericarditis."} {"id": "PMID:171958", "title": "Adult cytomegalovirus inclusion retino-uveitis.", "content": "A 27-year-old male renal transplant recipient acquired cytomegalovirus (CMV) infection of both eyes. This was characterized early by a distinctive necrotic retinitis with discrete advancing edges. A large exudative retinal detachment and hypopyon developed in one eye, and cultures from the anterior chamber aspirate grew CMV. Cytomegalovirus was also isolated from the urine and throat; after serial negative base-line titers, CMV antibody titer became positive. At autopsy CMV was isolated from lung, esophagus, and kidney tissue. Light and electron microscopic studies demonstrated extensive necrosis and disruption of the sensory retina and retinal pigment epithelium with exudative retinal detachments. The diseased retinal cells contained a multiplicity of viral particles in various stages of maturity. Cytomegalic inclusion-bearing cells were demonstrated in the choroid of the more severely affected eye.", "contents": "Adult cytomegalovirus inclusion retino-uveitis. A 27-year-old male renal transplant recipient acquired cytomegalovirus (CMV) infection of both eyes. This was characterized early by a distinctive necrotic retinitis with discrete advancing edges. A large exudative retinal detachment and hypopyon developed in one eye, and cultures from the anterior chamber aspirate grew CMV. Cytomegalovirus was also isolated from the urine and throat; after serial negative base-line titers, CMV antibody titer became positive. At autopsy CMV was isolated from lung, esophagus, and kidney tissue. Light and electron microscopic studies demonstrated extensive necrosis and disruption of the sensory retina and retinal pigment epithelium with exudative retinal detachments. The diseased retinal cells contained a multiplicity of viral particles in various stages of maturity. Cytomegalic inclusion-bearing cells were demonstrated in the choroid of the more severely affected eye."} {"id": "PMID:171953", "title": "Hepatitis in marmosets.", "content": "Some species of marmosets are susceptible, not only by parenteral inoculation but also by oral exposure, to human hepatitis A virus present in sera or feces. The stools of animals inoculated parenterally or orally contained fecal antigen during certain times of the incubation period and the early, acute phase of the disease; viruslike particles were present in feces of orally infected animals and such feces were infectious when inoculated into marmosets. The fecal antigen crossreacted both with the fecal virus particles and the immune-adherence antigen (see also papers by Purcell et al and Hilleman et al). The MS-1 and CR-326 strains of hepatitis A appeared antigenically similar or identical whereas the GB strain was antigenically different and may be associated with the recently defined type of hepatitis termed hepatitis C or hepatitis non-A/non-B. On repeated challenge hyperegic responses with diffuse liver cell necrosis occurred in some immune animals and this phenomenon must be taken into account in any future vaccination studies.", "contents": "Hepatitis in marmosets. Some species of marmosets are susceptible, not only by parenteral inoculation but also by oral exposure, to human hepatitis A virus present in sera or feces. The stools of animals inoculated parenterally or orally contained fecal antigen during certain times of the incubation period and the early, acute phase of the disease; viruslike particles were present in feces of orally infected animals and such feces were infectious when inoculated into marmosets. The fecal antigen crossreacted both with the fecal virus particles and the immune-adherence antigen (see also papers by Purcell et al and Hilleman et al). The MS-1 and CR-326 strains of hepatitis A appeared antigenically similar or identical whereas the GB strain was antigenically different and may be associated with the recently defined type of hepatitis termed hepatitis C or hepatitis non-A/non-B. On repeated challenge hyperegic responses with diffuse liver cell necrosis occurred in some immune animals and this phenomenon must be taken into account in any future vaccination studies."} {"id": "PMID:171954", "title": "Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis.", "content": "Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype.", "contents": "Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis. Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype."} {"id": "PMID:171959", "title": "Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis.", "content": "Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient.", "contents": "Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis. Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient."} {"id": "PMID:171955", "title": "Biophysical and biochemical properties of CR326 human hepatitis A virus.", "content": "CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 mmu spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests by infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, identical 27 mmu viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The buoyant density of the virus in CsCl was 1.34 and it was heat (60 C), ether, and acid stable but was destroyed by heat (100 C), formalin (1:4000), and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.", "contents": "Biophysical and biochemical properties of CR326 human hepatitis A virus. CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 mmu spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests by infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, identical 27 mmu viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The buoyant density of the virus in CsCl was 1.34 and it was heat (60 C), ether, and acid stable but was destroyed by heat (100 C), formalin (1:4000), and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus."} {"id": "PMID:171960", "title": "Neurologic complications with elevated antibody titer after acute hemorrhagic conjunctivitis.", "content": "Nine patients with polyradiculomyeloneuropathy after acute hemorrhagic conjunctivitis (AHC) infection were studied serologically. All except one patient had neutralization titers larger than or equal to 1:16 against the prototype J670/71 strain of AHC virus in at least one of their serum samples. The development of a significant fourfold rise in antibody titer against AHC virus occurred in one of the patients who developed neurologic complications five days after the onset of AHC infection.", "contents": "Neurologic complications with elevated antibody titer after acute hemorrhagic conjunctivitis. Nine patients with polyradiculomyeloneuropathy after acute hemorrhagic conjunctivitis (AHC) infection were studied serologically. All except one patient had neutralization titers larger than or equal to 1:16 against the prototype J670/71 strain of AHC virus in at least one of their serum samples. The development of a significant fourfold rise in antibody titer against AHC virus occurred in one of the patients who developed neurologic complications five days after the onset of AHC infection."} {"id": "PMID:171956", "title": "Viral hepatitis: clinical aspects.", "content": "In the majority of instances acute viral hepatitis resolves totally without sequelae. Fulminant hepatitis is a highly lethal lesion but 20 to 25 per cent of patients, principally young patients, survive. Survivors do not appear to develop chronic liver disease. Persistent viral hepatitis follows acute icteric hepatitis, both type B and non-B, in 10 to 12 per cent of patients. Six long-term HBs Ag carriers demonstrated HBs Ag clearance after 14-73 months. Chronic active viral hepatitis often progresses to cirrhosis. This progressive hepatitis appeared as a sequelae of acute icteric type B hepatitis in 3 per cent of 429 patients. In patients with chronic active type B hepatitis, low titers of HBs Ag are common.", "contents": "Viral hepatitis: clinical aspects. In the majority of instances acute viral hepatitis resolves totally without sequelae. Fulminant hepatitis is a highly lethal lesion but 20 to 25 per cent of patients, principally young patients, survive. Survivors do not appear to develop chronic liver disease. Persistent viral hepatitis follows acute icteric hepatitis, both type B and non-B, in 10 to 12 per cent of patients. Six long-term HBs Ag carriers demonstrated HBs Ag clearance after 14-73 months. Chronic active viral hepatitis often progresses to cirrhosis. This progressive hepatitis appeared as a sequelae of acute icteric type B hepatitis in 3 per cent of 429 patients. In patients with chronic active type B hepatitis, low titers of HBs Ag are common."} {"id": "PMID:171962", "title": "An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. II. Electron microscopy.", "content": "The electron microscopic features of the stages of divergent neuroepithelial differentiation in the solid implants of a transplantable mouse testicular teratoma (OTT-6050) are presented and compared to the sequential stages of cytogenesis that have been described in the developing avian and mammalian central nervous system. Primitive neuroepithelial tumor cells showed the features of undifferentiated multipotential matrix (or ventricular) cells of the neural tube. They formed primitive medullary rosettes, from which various transitions were traced to more differentiated, cilia-containing ependymoblastomatous rosettes; the transitional features included increased granular endoplasmic reticulum and microvilli formation. Glial differentiation was characterized by the presence of mature ependymal rosettes and of astrocytes containing glial filaments. Neuronal differentiation included the development of synapses and the presence of dense-core vesicles in nerve cell processes. No intermediate cell forms were found that suggested multiple lines of differentiation occurring within a single cell.", "contents": "An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. II. Electron microscopy. The electron microscopic features of the stages of divergent neuroepithelial differentiation in the solid implants of a transplantable mouse testicular teratoma (OTT-6050) are presented and compared to the sequential stages of cytogenesis that have been described in the developing avian and mammalian central nervous system. Primitive neuroepithelial tumor cells showed the features of undifferentiated multipotential matrix (or ventricular) cells of the neural tube. They formed primitive medullary rosettes, from which various transitions were traced to more differentiated, cilia-containing ependymoblastomatous rosettes; the transitional features included increased granular endoplasmic reticulum and microvilli formation. Glial differentiation was characterized by the presence of mature ependymal rosettes and of astrocytes containing glial filaments. Neuronal differentiation included the development of synapses and the presence of dense-core vesicles in nerve cell processes. No intermediate cell forms were found that suggested multiple lines of differentiation occurring within a single cell."} {"id": "PMID:171963", "title": "Effect of Ca++ on renal handling of PO4 identical to: evidence for two reabsorptive mechanisms.", "content": "The effect of hypercalcemia on renal handling of phosphorus was studied in parathyroidectomized rats during 1) extracellular volume expansion with normal saline (0.1 mg/100 g per min) and 2) parathyroid extract infusion (1 U/100 g per h). Hypercalcemia (serum calcium 12-15 mg/100 ml) blunted the phosphaturic response to volume expansion, both when serum calcium was raised acutely during volume expansion and when volume expansion was induced in rats with sustained hypercalcemia. These changes were not associated with significant variations in glomerular filtration rate and serum concentration of phosphorus. Hypercalcemia failed to alter the phosphaturic response and the increase in urinary cyclic AMP excretion following both continuous infusion and a single injection of parathyroid extract. These results are consistent with two components of tubular reabsorption of phosphorus. The first is suppressed by extracellular volume expansion and stimulated by hypercalcemia. The second is suppressed by parathyroid hormone and is not affected by hypercalcemia.", "contents": "Effect of Ca++ on renal handling of PO4 identical to: evidence for two reabsorptive mechanisms. The effect of hypercalcemia on renal handling of phosphorus was studied in parathyroidectomized rats during 1) extracellular volume expansion with normal saline (0.1 mg/100 g per min) and 2) parathyroid extract infusion (1 U/100 g per h). Hypercalcemia (serum calcium 12-15 mg/100 ml) blunted the phosphaturic response to volume expansion, both when serum calcium was raised acutely during volume expansion and when volume expansion was induced in rats with sustained hypercalcemia. These changes were not associated with significant variations in glomerular filtration rate and serum concentration of phosphorus. Hypercalcemia failed to alter the phosphaturic response and the increase in urinary cyclic AMP excretion following both continuous infusion and a single injection of parathyroid extract. These results are consistent with two components of tubular reabsorption of phosphorus. The first is suppressed by extracellular volume expansion and stimulated by hypercalcemia. The second is suppressed by parathyroid hormone and is not affected by hypercalcemia."} {"id": "PMID:171964", "title": "Effect of 25(OH)vitamin D3 on urinary excretion of cyclic adenosine monophosphate.", "content": "To further evaluate the effect of 25(OH)vitamin D3 (25(OH)vit D3) on renal handling of phosphorus, fractional excretion of phosphorus (CP/CIn) and urinary excretion of cyclic AMP (UcAMP) were measured in the following groups of animals: 1) intact rats receiving intravenously 25(OH)vit D3. 2a) Parathyroidectomized (PTX) rats receiving a continuous infusion of parathyroid hormone (PTH). 2b) PTX rats undergoing continuous infusion of PTH and receiving intravenously 25(OH)vit D3. In group 1 a decrease in CP/CIn from a control value of 0.210 +/- 0.064 (kappa +/- SE) to 0.052 +/- 0.017 (P less than 0.001) during 25(OH)vit D3 infusion was associated with a corresponding decrease in UcAMP from 182 +/- 18 to 87 +/- 8 pmol/min (P less than 0.001). In group 2a an increase in CP/CIn from a control value of 0.031 +/- 0.014 to 0.365 +/- 0.017 during PTH infusion was associated with a corresponding increase in UcAMP from 76 +/- 17 to 330 +/- 51 pmol/min (P less than 0.001). In group 2b a decrease in CP/CIn from 0.365 +/- 0.017 to 0.256 +/- 0.011 (P less than 0.01) during 25(OH)vit D3 infusion was associated with a decrease in UcAMP from 356 +/- 63 to 191 +/- 33 pmol/min (P less than 0.01). These results indicate that the blunting of the phosphaturic response to PTH by 25(OH)vit D3 is associated with a decrease in UcAMP. This observation suggests that the mechanism underlying the enhanced tubular reabsorption of phosphorus is inhibition of the PTH-induced activation of adenylate cyclase in the kidney.", "contents": "Effect of 25(OH)vitamin D3 on urinary excretion of cyclic adenosine monophosphate. To further evaluate the effect of 25(OH)vitamin D3 (25(OH)vit D3) on renal handling of phosphorus, fractional excretion of phosphorus (CP/CIn) and urinary excretion of cyclic AMP (UcAMP) were measured in the following groups of animals: 1) intact rats receiving intravenously 25(OH)vit D3. 2a) Parathyroidectomized (PTX) rats receiving a continuous infusion of parathyroid hormone (PTH). 2b) PTX rats undergoing continuous infusion of PTH and receiving intravenously 25(OH)vit D3. In group 1 a decrease in CP/CIn from a control value of 0.210 +/- 0.064 (kappa +/- SE) to 0.052 +/- 0.017 (P less than 0.001) during 25(OH)vit D3 infusion was associated with a corresponding decrease in UcAMP from 182 +/- 18 to 87 +/- 8 pmol/min (P less than 0.001). In group 2a an increase in CP/CIn from a control value of 0.031 +/- 0.014 to 0.365 +/- 0.017 during PTH infusion was associated with a corresponding increase in UcAMP from 76 +/- 17 to 330 +/- 51 pmol/min (P less than 0.001). In group 2b a decrease in CP/CIn from 0.365 +/- 0.017 to 0.256 +/- 0.011 (P less than 0.01) during 25(OH)vit D3 infusion was associated with a decrease in UcAMP from 356 +/- 63 to 191 +/- 33 pmol/min (P less than 0.01). These results indicate that the blunting of the phosphaturic response to PTH by 25(OH)vit D3 is associated with a decrease in UcAMP. This observation suggests that the mechanism underlying the enhanced tubular reabsorption of phosphorus is inhibition of the PTH-induced activation of adenylate cyclase in the kidney."} {"id": "PMID:171961", "title": "Daily living group: focus on transition from hospital to community.", "content": "A group (Daily Living Group) that prepares patients for discharge from a psychiatric hospital was formulated to provide patients with information on activities essential for their integration into the outside community. The information included the use of support systems in the hospital setting to aid in bridging the gap between hospital and community, as well as emphasis on the patients' leisure interests, community resources, and environment outside the hospital. The group then gave the patients the opportunity to apply what they learned, that is, practical experience in working through their problems. Patients with an investment in making behavioral changes responded well, but those with no investment lowered the morale of the group when coerced into attending.", "contents": "Daily living group: focus on transition from hospital to community. A group (Daily Living Group) that prepares patients for discharge from a psychiatric hospital was formulated to provide patients with information on activities essential for their integration into the outside community. The information included the use of support systems in the hospital setting to aid in bridging the gap between hospital and community, as well as emphasis on the patients' leisure interests, community resources, and environment outside the hospital. The group then gave the patients the opportunity to apply what they learned, that is, practical experience in working through their problems. Patients with an investment in making behavioral changes responded well, but those with no investment lowered the morale of the group when coerced into attending."} {"id": "PMID:171975", "title": "The fine structure of the urinary bladder epithelium in the hartebeest, Alcelaphus buselaphus cokii and the Masai giraffe, Giraffa camelopardalis tippelskirchi.", "content": "The microscopic anatomy and ultrastructure of the urinary bladder epithelium are described in the giraffe and the hartebeest. Differences between the epithelial cell layers of the urinary bladder are described. Cells belonging to different layers show variations in their cell organelles and inclusions. The surface cells contain relatively few fusiform and spherical vesicles.", "contents": "The fine structure of the urinary bladder epithelium in the hartebeest, Alcelaphus buselaphus cokii and the Masai giraffe, Giraffa camelopardalis tippelskirchi. The microscopic anatomy and ultrastructure of the urinary bladder epithelium are described in the giraffe and the hartebeest. Differences between the epithelial cell layers of the urinary bladder are described. Cells belonging to different layers show variations in their cell organelles and inclusions. The surface cells contain relatively few fusiform and spherical vesicles."} {"id": "PMID:171976", "title": "The isolation of epithelial cells from the rat epididymis.", "content": "Epithelial cells from the epididymis were released by digesting the chopped epididymis with pronase followed by collagenase plus hyaluronidase. The epithelial cells were further separated from contaminating cell types by differential centrifugation and sedimentation at unit gravity through a gradient of sucrose in Ringer. The isolated cells remained viable as judged by the exclusion of trypan blue. The cells respired in the presence of glucose and the rate of respiration was not altered by the subsequent addition of pyruvate.", "contents": "The isolation of epithelial cells from the rat epididymis. Epithelial cells from the epididymis were released by digesting the chopped epididymis with pronase followed by collagenase plus hyaluronidase. The epithelial cells were further separated from contaminating cell types by differential centrifugation and sedimentation at unit gravity through a gradient of sucrose in Ringer. The isolated cells remained viable as judged by the exclusion of trypan blue. The cells respired in the presence of glucose and the rate of respiration was not altered by the subsequent addition of pyruvate."} {"id": "PMID:171977", "title": "Limbic neuronal firing rates in man during administration of nitrous oxide--oxygen or sodium thiopental.", "content": "Electroencephalographic activity and extracellular discharges from neurons in deep temporal lobe structures were recorded from fine wire microelectrodes chronically implanted in seven psychomotor epileptic patients for diagnostic localization of seizure foci. In four patients, inhalation of 80 per cent nitrous oxide resulted in loss of consciousness without change in firing rates of temporal lobe neurons (n = 22). In all seven patients, thiopental (400 or 200 mg, iv) decreased limbic neuronal firing rates (n = 38) until the return of wakefulness. In only three of these patients, however, did the firing rates of the neurons (n = 19) decrease significantly (P less than .05). Thiopental suppression of unit activity was not related to systemic hypoxia. This study demonstrates that anesthetic induction with nitrous oxide-oxygen does not significantly affect the firing of neurons in various regions of the human limbic system, which may explain the incidence of patient awareness reported when nitrous oxide-oxygen is administered alone. Thiopental depresses the firing of limbic neurons, and this may account in part for the temporary confusion and amnesia often manifested by patients recovering from the effects of thiopental.", "contents": "Limbic neuronal firing rates in man during administration of nitrous oxide--oxygen or sodium thiopental. Electroencephalographic activity and extracellular discharges from neurons in deep temporal lobe structures were recorded from fine wire microelectrodes chronically implanted in seven psychomotor epileptic patients for diagnostic localization of seizure foci. In four patients, inhalation of 80 per cent nitrous oxide resulted in loss of consciousness without change in firing rates of temporal lobe neurons (n = 22). In all seven patients, thiopental (400 or 200 mg, iv) decreased limbic neuronal firing rates (n = 38) until the return of wakefulness. In only three of these patients, however, did the firing rates of the neurons (n = 19) decrease significantly (P less than .05). Thiopental suppression of unit activity was not related to systemic hypoxia. This study demonstrates that anesthetic induction with nitrous oxide-oxygen does not significantly affect the firing of neurons in various regions of the human limbic system, which may explain the incidence of patient awareness reported when nitrous oxide-oxygen is administered alone. Thiopental depresses the firing of limbic neurons, and this may account in part for the temporary confusion and amnesia often manifested by patients recovering from the effects of thiopental."} {"id": "PMID:171980", "title": "Recovery of transmissible gastroenteritis virus from chronically infected experimental pigs.", "content": "Transmissible gastroenteritis (TGE) virus was reisolated from pulmonary and intestinal tissues from 6 of 9 chronically infected experimental pigs (principals) necropsied 30 to 104 days after inoculation. Tissue homogenates (lung and small intestine) from the principals were prepared and inoculated into 3- to 5-day-old gnotobiotic pigs. The virus reisolated from the tissue homogenates produced a milder disease on 1st passage and a more severe disease on 2nd passage. The chronically infected experimental pigs (principals) developed serum-neutralization titers to TGE of 1:30 to 1:525. There appeared to be no relationship between serum titers and reisolation of TGE virus from the 9 principals. The persistence of virus in lung or intestine to 104 days indicates the recovered (or carrier) pig may be considered the primary source of TGE virus infection.", "contents": "Recovery of transmissible gastroenteritis virus from chronically infected experimental pigs. Transmissible gastroenteritis (TGE) virus was reisolated from pulmonary and intestinal tissues from 6 of 9 chronically infected experimental pigs (principals) necropsied 30 to 104 days after inoculation. Tissue homogenates (lung and small intestine) from the principals were prepared and inoculated into 3- to 5-day-old gnotobiotic pigs. The virus reisolated from the tissue homogenates produced a milder disease on 1st passage and a more severe disease on 2nd passage. The chronically infected experimental pigs (principals) developed serum-neutralization titers to TGE of 1:30 to 1:525. There appeared to be no relationship between serum titers and reisolation of TGE virus from the 9 principals. The persistence of virus in lung or intestine to 104 days indicates the recovered (or carrier) pig may be considered the primary source of TGE virus infection."} {"id": "PMID:171981", "title": "Comparative characteristics of three cytomegaloviruses from rodents.", "content": "One cytomegalovirus isolate from the vole (Microtus arvalis) and 2 cutomegalovirus strains from mice (Apodemus sylvatious and Mus musculus) were compared. The rates of inactivation of these 3 viruses were virtually identical after each of 3 treatments: Repeated cycles of freezing and thawing, ultrasonic vibration, and exposure to trypsin and chymotrypsin. The replication of the 3 viruses was similar in each of 3 types of mouse embryo fibroblast cells tested. A number of other characteristics of the vole isolate were the same as those of the mouse strains, including buoyant density (1.20 g/cu cm), enhanced plaquing efficiency in diethylaminoethyl-dextran, and induction of an abortive replication cycle in human cells. The 3 viruses were indistinguishable with regard to their antigenic characteristics, and electron microscopic examination revealed that the nucleocapsids and enveloped virions of the 3 viruses were indistinguishable.", "contents": "Comparative characteristics of three cytomegaloviruses from rodents. One cytomegalovirus isolate from the vole (Microtus arvalis) and 2 cutomegalovirus strains from mice (Apodemus sylvatious and Mus musculus) were compared. The rates of inactivation of these 3 viruses were virtually identical after each of 3 treatments: Repeated cycles of freezing and thawing, ultrasonic vibration, and exposure to trypsin and chymotrypsin. The replication of the 3 viruses was similar in each of 3 types of mouse embryo fibroblast cells tested. A number of other characteristics of the vole isolate were the same as those of the mouse strains, including buoyant density (1.20 g/cu cm), enhanced plaquing efficiency in diethylaminoethyl-dextran, and induction of an abortive replication cycle in human cells. The 3 viruses were indistinguishable with regard to their antigenic characteristics, and electron microscopic examination revealed that the nucleocapsids and enveloped virions of the 3 viruses were indistinguishable."} {"id": "PMID:171982", "title": "Methylmercury: effect on oncogenic and nononcogenic viruses in mice.", "content": "Mice fed methylmercury chloride at dosages of 1 or 10 ppm for 84 days had significantly higher mortality rates when inoculated with encephalomyocarditis virus (nononcogenic) than did nonmethylmercury-treated mice. However, methylmercury fed to mice which were inoculated with Rauscher leukemia virus (oncogenic) did not alter the course of neoplasia. These results demonstrate that prolonged exposure to subclinical concentrations of methylmercury increased susceptibility of a host to a nononcogenic, but not to an oncogenic, virus.", "contents": "Methylmercury: effect on oncogenic and nononcogenic viruses in mice. Mice fed methylmercury chloride at dosages of 1 or 10 ppm for 84 days had significantly higher mortality rates when inoculated with encephalomyocarditis virus (nononcogenic) than did nonmethylmercury-treated mice. However, methylmercury fed to mice which were inoculated with Rauscher leukemia virus (oncogenic) did not alter the course of neoplasia. These results demonstrate that prolonged exposure to subclinical concentrations of methylmercury increased susceptibility of a host to a nononcogenic, but not to an oncogenic, virus."} {"id": "PMID:171983", "title": "Effects of intramedullary injection of methiodal and lidocaine on spinal cords of dogs.", "content": "A solution of methiodal sodium (20%) and lidocaine HCl (0.20%) was given by intramedullary injection into the lumbar spinal cords of 12 anesthetized dogs (group I). Two control groups of 12 dogs each were subjected to needle placement only or were given 5% dextrose. The results showed that both solutions given by intramedullary injection caused severe spinal cord malacia and cavitation in 2 group I dogs and in 1 group III dog.", "contents": "Effects of intramedullary injection of methiodal and lidocaine on spinal cords of dogs. A solution of methiodal sodium (20%) and lidocaine HCl (0.20%) was given by intramedullary injection into the lumbar spinal cords of 12 anesthetized dogs (group I). Two control groups of 12 dogs each were subjected to needle placement only or were given 5% dextrose. The results showed that both solutions given by intramedullary injection caused severe spinal cord malacia and cavitation in 2 group I dogs and in 1 group III dog."} {"id": "PMID:171984", "title": "Cell-to-cell attachments and associations in tumors induced by CELO virus or virus-transformed cells in hamsters.", "content": "Cell-to-cell attachments or associations in expermentally induced sarcoma of chicken embryo lethal orphan virus (avian adenovirus) origin were studied in hamsters by electron microscopic examination. In many instances, the neoplastic cells seemed to be held together either by desmosome-like structures or an \"interlocking\" of their apposing plasma membranes. Less frequently, the cells were attached by button-like projections between the cell surfaces. Only rarely, interdigitation occurred between filopodial processes of cell surface of adjoining cells.", "contents": "Cell-to-cell attachments and associations in tumors induced by CELO virus or virus-transformed cells in hamsters. Cell-to-cell attachments or associations in expermentally induced sarcoma of chicken embryo lethal orphan virus (avian adenovirus) origin were studied in hamsters by electron microscopic examination. In many instances, the neoplastic cells seemed to be held together either by desmosome-like structures or an \"interlocking\" of their apposing plasma membranes. Less frequently, the cells were attached by button-like projections between the cell surfaces. Only rarely, interdigitation occurred between filopodial processes of cell surface of adjoining cells."} {"id": "PMID:171985", "title": "Immunoglobulins and anti-Marek's disease virus antibody synthesis in chickens after passive immunization with immunoglobulin Y anti-Marek's disease virus antibody.", "content": "The effect of passive immunization with immunoglobulin Y (IgY) antibody against Marek's disease virus (MDV) was examined in MDV-susceptible chickens. The production of IgY, immunoglobulin M, and probably also immunoglobulin A was depressed in passively immunized chickens when compared with that in MDV-exposed chickens which had not been given IgY anti-MDV antibody. In passively immunized chickens, the synthesis of immunoglobulin M and IgY anti-MDV antibodies in response to MDV infection also was delayed as determined by agar gel precipitin and indirect fluorescence antibody tests.", "contents": "Immunoglobulins and anti-Marek's disease virus antibody synthesis in chickens after passive immunization with immunoglobulin Y anti-Marek's disease virus antibody. The effect of passive immunization with immunoglobulin Y (IgY) antibody against Marek's disease virus (MDV) was examined in MDV-susceptible chickens. The production of IgY, immunoglobulin M, and probably also immunoglobulin A was depressed in passively immunized chickens when compared with that in MDV-exposed chickens which had not been given IgY anti-MDV antibody. In passively immunized chickens, the synthesis of immunoglobulin M and IgY anti-MDV antibodies in response to MDV infection also was delayed as determined by agar gel precipitin and indirect fluorescence antibody tests."} {"id": "PMID:171986", "title": "Thermostability of duck hepatitis virus.", "content": "The comparative thermostability of 4 duck hepatitis (DH) viruses were tested at various temperatures for different times. Titer of duckling-passaged, pathogenic DH virus decreased from 10(4.50) to 10(2.33) and 10(2.20) median infective doses (ID50/0.1 ml, respectively, in 2 tests; titer of chicken embryo-passaged, nonpathogenic, but embryo-lethal, DH virus decreased from 10(6.00) to 10(0.46) and from 10(6.62) to 10(0.63) ID50/0.1 ml, respectively; duck embryo fibroblast culture-passaged and duck embryo liver cell culture-passaged, chicken ebryo-infective, but nonlethal, DH viruses were completely inactivated or nearly so after being kept at 56 C for 30 minutes. Duckling-passaged DH virus was not detected on day 21, whereas 10(0.62) ID50 of chicken embryo-passaged DH virus per 0.1 ml remained on day 32 when being kept at 37 C. Titer of chicken embryo-passaged DH virus decreased from 10(7.00) to 10(1.16) ID50/0.1 ml after being kept at room at room temperature for 150 days, to 10(5.17) ID50/0.1 ml after being kept at 4 C for 70 weeks, to 10(6.17) ID50/0.1 ml after being kept at -20 C for 70 weeks, and to 10(6.38) ID50/0.1 ml after being kept at -60 C for 1 year.", "contents": "Thermostability of duck hepatitis virus. The comparative thermostability of 4 duck hepatitis (DH) viruses were tested at various temperatures for different times. Titer of duckling-passaged, pathogenic DH virus decreased from 10(4.50) to 10(2.33) and 10(2.20) median infective doses (ID50/0.1 ml, respectively, in 2 tests; titer of chicken embryo-passaged, nonpathogenic, but embryo-lethal, DH virus decreased from 10(6.00) to 10(0.46) and from 10(6.62) to 10(0.63) ID50/0.1 ml, respectively; duck embryo fibroblast culture-passaged and duck embryo liver cell culture-passaged, chicken ebryo-infective, but nonlethal, DH viruses were completely inactivated or nearly so after being kept at 56 C for 30 minutes. Duckling-passaged DH virus was not detected on day 21, whereas 10(0.62) ID50 of chicken embryo-passaged DH virus per 0.1 ml remained on day 32 when being kept at 37 C. Titer of chicken embryo-passaged DH virus decreased from 10(7.00) to 10(1.16) ID50/0.1 ml after being kept at room at room temperature for 150 days, to 10(5.17) ID50/0.1 ml after being kept at 4 C for 70 weeks, to 10(6.17) ID50/0.1 ml after being kept at -20 C for 70 weeks, and to 10(6.38) ID50/0.1 ml after being kept at -60 C for 1 year."} {"id": "PMID:171987", "title": "[Influence of some substances on the titration of a poliovirus aqueous suspension (author's transl)].", "content": "Important changes of virus titer are observed when low concentration of mineral salts (NaCl, MgCl2, AlCl3) or detergents (Tween 80) are added to a poliovirus suspension in distilled water. Calf serum addition to these suspensions induces new variations of virus titer. The highest titre is obtained in isotonic medium with calf serum.", "contents": "[Influence of some substances on the titration of a poliovirus aqueous suspension (author's transl)]. Important changes of virus titer are observed when low concentration of mineral salts (NaCl, MgCl2, AlCl3) or detergents (Tween 80) are added to a poliovirus suspension in distilled water. Calf serum addition to these suspensions induces new variations of virus titer. The highest titre is obtained in isotonic medium with calf serum."} {"id": "PMID:171988", "title": "[Effect of sodium salicylate on the \"in vitro\" development of RNA viruses (author's transl)].", "content": "Sodium salicylate 10(-3) M is able to limit the number of plaques induced by RNA viruses on monkey kidney cell cultures (Cercopithecus aethiops and Macaccus rhesus). However, the inhibition rate changes with the virus type or even the strain used. Poliovirus 2, Coxsackie B3, echovirus and reovirus 1 were the most susceptible to the inhibitory effect of the drug. Latent infection caused by SV5 decreases the antiviral activity of salicylate. The stages of the poliovirus type 2 growth affected by sodium salicylate, were studied. The drug has no direct activity on the infectivity of the virus. It decreases adsorption and penetration. In spite of heavy virus concentration (10(-5,5) to 10(-7)) ID/ml) the eclipse phase is delayed about 3 hours. After 6 hours, viral maturation proceeds and reaches the same level as the controls, and virus quantities recovered are equivalent after 12 hours. Viral infectious RNA fails to induce plaques on salicylate treated cultures. The drug seems to act during the eclipse phase.", "contents": "[Effect of sodium salicylate on the \"in vitro\" development of RNA viruses (author's transl)]. Sodium salicylate 10(-3) M is able to limit the number of plaques induced by RNA viruses on monkey kidney cell cultures (Cercopithecus aethiops and Macaccus rhesus). However, the inhibition rate changes with the virus type or even the strain used. Poliovirus 2, Coxsackie B3, echovirus and reovirus 1 were the most susceptible to the inhibitory effect of the drug. Latent infection caused by SV5 decreases the antiviral activity of salicylate. The stages of the poliovirus type 2 growth affected by sodium salicylate, were studied. The drug has no direct activity on the infectivity of the virus. It decreases adsorption and penetration. In spite of heavy virus concentration (10(-5,5) to 10(-7)) ID/ml) the eclipse phase is delayed about 3 hours. After 6 hours, viral maturation proceeds and reaches the same level as the controls, and virus quantities recovered are equivalent after 12 hours. Viral infectious RNA fails to induce plaques on salicylate treated cultures. The drug seems to act during the eclipse phase."} {"id": "PMID:171989", "title": "[Isolation of \"Neisseria elongata\" and \"Moraxella urethralis\" (author's transl)].", "content": "A strain of Neisseria elongata and a strain of Moraxella urethralis have been recently isolated from pathological material in the course of a systematic search for rodshaped oxidase positive and Gram negative micro-organisms. The morphological, cultural and biochemical characters of these fewly known strains of which pathogenicity is not clearly defined, are reported in the present paper together with some comments.", "contents": "[Isolation of \"Neisseria elongata\" and \"Moraxella urethralis\" (author's transl)]. A strain of Neisseria elongata and a strain of Moraxella urethralis have been recently isolated from pathological material in the course of a systematic search for rodshaped oxidase positive and Gram negative micro-organisms. The morphological, cultural and biochemical characters of these fewly known strains of which pathogenicity is not clearly defined, are reported in the present paper together with some comments."} {"id": "PMID:171990", "title": "Fish health--some concepts, constraints, and comparisons.", "content": "This has been an overview of fish health, a comparison of some aspects of fish husbandry with other animal husbandry, and comments concerning fish health research--especially where it is going. The 1972 disease survey identified current problems; it ranked the problems according to priority. More important, research effort has been redirected. Problems of highest priority are receiving the greatest attention; those of lesser priority are receiving the appropriately lesser attention. Just as veterinary and human medical research have become more mission-oriented, fish health research has also become much more of a problem-solving activity. There are fewer dollars; they must be used wisely and they must produce. Research in fish health is expected to yield usable information that will be of significant help in producing better fishes. If destined for the table, such fishes should convert feeds rapidly and efficiently, and they should not suffer losses from diseases. If intended for stocking, such fishes should be capable of thriving in the environment and of surviving to fulfill their destiny.", "contents": "Fish health--some concepts, constraints, and comparisons. This has been an overview of fish health, a comparison of some aspects of fish husbandry with other animal husbandry, and comments concerning fish health research--especially where it is going. The 1972 disease survey identified current problems; it ranked the problems according to priority. More important, research effort has been redirected. Problems of highest priority are receiving the greatest attention; those of lesser priority are receiving the appropriately lesser attention. Just as veterinary and human medical research have become more mission-oriented, fish health research has also become much more of a problem-solving activity. There are fewer dollars; they must be used wisely and they must produce. Research in fish health is expected to yield usable information that will be of significant help in producing better fishes. If destined for the table, such fishes should convert feeds rapidly and efficiently, and they should not suffer losses from diseases. If intended for stocking, such fishes should be capable of thriving in the environment and of surviving to fulfill their destiny."} {"id": "PMID:171997", "title": "The mechanism of action of 3-deazauridine in tumor cells sensitive and resistant to arabinosylcytosine.", "content": "Deazauridine inhibited growth of tumor cells in culture and in culture and in vivo; this agent was significantly more effective against L1210/AraC than against the parent sensitive line. Inhibition of growth of tumor cells in culture was prevented by uridine and cytidine and was partially alleviated by deoxycytidine, but not by deoxyuridine or thymidine. DeazaUR inhibited nucleic acid synthesis but not protein synthesis in tumor cells in culture; deoxycytidine alleviated inhibition of nucleic acid synthesis. The labeling of pyrimidine ribonucleotides by 6-14C-orotic acid was inhbited by deazaUR. DeazaUR treatment of tumor cells in culture resulted in increased uptake of cytidine-3H into RNA, whereas uridine-3H uptake into RNA was inhibited. Labelling of DNA by uridine-3H/ and cytidine-H was inhibited by deazaUR. Pools of CMP, CDP, and CTP decreased markedly during deazaUR treatment of L1210 cells in culture and in vivo. These observations in growing cells pointed to deazaUR inhibition of the synthesis of cytidylic acid. Deazauridine 5'-triphosphate was found to be an inhibitor of the synthesis of CTP from UTP catalyzed by enzyme preparations from L1210 cells. This observation is in agreement with those of McPartland et al.19 that deazaUTP inhibited CTP synthetase purified from calf liver. Deazauridine treatment of L1210 cells in culture stimulated the uptake of deoxycytidine-3H into DNA while inhibiting the uptake of 3H-labeled deoxyuridine, thymidine, deoxyadenosine, and deoxyguanosine. Intracellular pools of dCTP were decreased by deazauridine treatment in L1210 cells in culture and in vivo. Deazauridine 5'-diphosphate inhibited the enzymatic reduction of pyrimidine ribonucleoside 5'-diphosphates to the corresponding deoxyribonucleotides. These results are consistent with the view that deazauridine, after its uptake and intracellular phosphorylation, strongly inhibits the formation of CTP. This is considered to be the primary metabolic effect of the analog. A secondary effect appears to be an inhibition of dCTP formation.", "contents": "The mechanism of action of 3-deazauridine in tumor cells sensitive and resistant to arabinosylcytosine. Deazauridine inhibited growth of tumor cells in culture and in culture and in vivo; this agent was significantly more effective against L1210/AraC than against the parent sensitive line. Inhibition of growth of tumor cells in culture was prevented by uridine and cytidine and was partially alleviated by deoxycytidine, but not by deoxyuridine or thymidine. DeazaUR inhibited nucleic acid synthesis but not protein synthesis in tumor cells in culture; deoxycytidine alleviated inhibition of nucleic acid synthesis. The labeling of pyrimidine ribonucleotides by 6-14C-orotic acid was inhbited by deazaUR. DeazaUR treatment of tumor cells in culture resulted in increased uptake of cytidine-3H into RNA, whereas uridine-3H uptake into RNA was inhibited. Labelling of DNA by uridine-3H/ and cytidine-H was inhibited by deazaUR. Pools of CMP, CDP, and CTP decreased markedly during deazaUR treatment of L1210 cells in culture and in vivo. These observations in growing cells pointed to deazaUR inhibition of the synthesis of cytidylic acid. Deazauridine 5'-triphosphate was found to be an inhibitor of the synthesis of CTP from UTP catalyzed by enzyme preparations from L1210 cells. This observation is in agreement with those of McPartland et al.19 that deazaUTP inhibited CTP synthetase purified from calf liver. Deazauridine treatment of L1210 cells in culture stimulated the uptake of deoxycytidine-3H into DNA while inhibiting the uptake of 3H-labeled deoxyuridine, thymidine, deoxyadenosine, and deoxyguanosine. Intracellular pools of dCTP were decreased by deazauridine treatment in L1210 cells in culture and in vivo. Deazauridine 5'-diphosphate inhibited the enzymatic reduction of pyrimidine ribonucleoside 5'-diphosphates to the corresponding deoxyribonucleotides. These results are consistent with the view that deazauridine, after its uptake and intracellular phosphorylation, strongly inhibits the formation of CTP. This is considered to be the primary metabolic effect of the analog. A secondary effect appears to be an inhibition of dCTP formation."} {"id": "PMID:172007", "title": "Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens.", "content": "The comparative bactericidal activity of penicillin G, carbenicillin, clindamycin, and metronidazole against eight susceptible strains of Bacteroides fragilis and four strains of Clostridium perfringens was determined by performing colony counts anaerobically of cultures incubated in brucella broth. With the B. fragilis strains, there was a lag phase of growth of approximately 8 h, during which time metronidazole did not reduce the colony counts. However, within 4 h of the onset of exponential growth, metronidazole caused an abrupt decrease in counts to less than 100 colonies per ml in all strains tested. Moreover, in two strains in which the bactericidal rate was followed hourly, a 3- to 6-log decrease occurred over 1 h or less. In contrast, penicillin G and carbenicillin caused a gradual decline in colony counts from the start of approximately 1 log for each 8-h interval and were bactericidal for all strains tested. Clindamycin demonstrated the slowest bactericidal activity and for 25% of the strains was only bacteriostatic. With the C. perfringens strains, after a lag phase of 4 h, an abrupt decrease in colony counts also occurred with metronidazole, whereas penicillin and clindamycin again demonstrated more gradual killing effects. These studies showed a unique, time-related bactericidal action of metronidazole as compared with the other three antimicrobial agents.", "contents": "Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. The comparative bactericidal activity of penicillin G, carbenicillin, clindamycin, and metronidazole against eight susceptible strains of Bacteroides fragilis and four strains of Clostridium perfringens was determined by performing colony counts anaerobically of cultures incubated in brucella broth. With the B. fragilis strains, there was a lag phase of growth of approximately 8 h, during which time metronidazole did not reduce the colony counts. However, within 4 h of the onset of exponential growth, metronidazole caused an abrupt decrease in counts to less than 100 colonies per ml in all strains tested. Moreover, in two strains in which the bactericidal rate was followed hourly, a 3- to 6-log decrease occurred over 1 h or less. In contrast, penicillin G and carbenicillin caused a gradual decline in colony counts from the start of approximately 1 log for each 8-h interval and were bactericidal for all strains tested. Clindamycin demonstrated the slowest bactericidal activity and for 25% of the strains was only bacteriostatic. With the C. perfringens strains, after a lag phase of 4 h, an abrupt decrease in colony counts also occurred with metronidazole, whereas penicillin and clindamycin again demonstrated more gradual killing effects. These studies showed a unique, time-related bactericidal action of metronidazole as compared with the other three antimicrobial agents."} {"id": "PMID:172001", "title": "Foreign body removal: a new role for the fiberoptic bronchoscope.", "content": "Artificial and animal lung models initially were used to investigate the removal of foreign bodies from the tracheobronchial tree with the flexible fiberoptic bronchoscope. Different extraction instruments (claw, basket, forceps, and balloon catheter) were passed separately through the channel of the bronchofiberscope, and tested for usefulness prior to human application. The Fogarty balloon catheter served as a valuable aid in dislodging impacted objects so that the operator could then grasp them with the claw, basket or forceps. The wire claw recovered many of the metallic and organic objects, the wire basket was successful in retrieving only the bulky objects and the forceps (ACMI) was effective in capturing all of the metallic foreign bodies. These techniques, developed in our laboratory, are now being used to augment rigid bronchoscopy in the removal of foreign bodies from adults and older children. At the present time fiberoptic foreign body removal is not recommended for pediatric cases because of the small diameter of the trachea and glottis in infants and young children.", "contents": "Foreign body removal: a new role for the fiberoptic bronchoscope. Artificial and animal lung models initially were used to investigate the removal of foreign bodies from the tracheobronchial tree with the flexible fiberoptic bronchoscope. Different extraction instruments (claw, basket, forceps, and balloon catheter) were passed separately through the channel of the bronchofiberscope, and tested for usefulness prior to human application. The Fogarty balloon catheter served as a valuable aid in dislodging impacted objects so that the operator could then grasp them with the claw, basket or forceps. The wire claw recovered many of the metallic and organic objects, the wire basket was successful in retrieving only the bulky objects and the forceps (ACMI) was effective in capturing all of the metallic foreign bodies. These techniques, developed in our laboratory, are now being used to augment rigid bronchoscopy in the removal of foreign bodies from adults and older children. At the present time fiberoptic foreign body removal is not recommended for pediatric cases because of the small diameter of the trachea and glottis in infants and young children."} {"id": "PMID:172004", "title": "[Juvenile hormone in diapausing Pieris brassicae and mutations. Tetrahydrofolic acid and pterins incubated in chrysalids, provoking ontogenic and mutagenic genetic information alterations in Drosophila melanogaster].", "content": "Study of AMPc phosphodiesterase shows presence of JH in diapausing chrysalids and antogonistic action of FH and pterines. Study of farnesoldeshydrogenase and farnesal deshydrogenase in Dm shows that FH4 and pterines inhibite FDH, active ADH. Conclusion is JH in diapause chrysalides is active factor with FH4 provoking genesis of pigmentary mutation, cellular proliferation or growth deficiencies. Comparison with JH+FH4+ teromes incubated in Bar (Muller 5) mutants of Dm in place of diapausing chrysalids reproduce larval deficiences, mosaics and mutations observed in precedent experiments.", "contents": "[Juvenile hormone in diapausing Pieris brassicae and mutations. Tetrahydrofolic acid and pterins incubated in chrysalids, provoking ontogenic and mutagenic genetic information alterations in Drosophila melanogaster]. Study of AMPc phosphodiesterase shows presence of JH in diapausing chrysalids and antogonistic action of FH and pterines. Study of farnesoldeshydrogenase and farnesal deshydrogenase in Dm shows that FH4 and pterines inhibite FDH, active ADH. Conclusion is JH in diapause chrysalides is active factor with FH4 provoking genesis of pigmentary mutation, cellular proliferation or growth deficiencies. Comparison with JH+FH4+ teromes incubated in Bar (Muller 5) mutants of Dm in place of diapausing chrysalids reproduce larval deficiences, mosaics and mutations observed in precedent experiments."} {"id": "PMID:172008", "title": "Inhibition of experimental deoxyribonucleic acid virus-induced encephalitis by 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate.", "content": "9-beta-d-Arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-beta-d-arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation.", "contents": "Inhibition of experimental deoxyribonucleic acid virus-induced encephalitis by 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate. 9-beta-d-Arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-beta-d-arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation."} {"id": "PMID:172003", "title": "[Proceedings: Role of endogenous and exogenous ACTH on aldosterone secretion (author's transl)].", "content": "The role of ACTH in the control of aldosterone secretion has been investigated in volunteers under a normal sodium diet. Endogenous ACTH suppression by dexamethasone (DXM) does not alter the plasma aldosterone (PA) response to 20 mg furosemide since identical PA increases are observed in control subjects and in subjects with DXM suppressed endogenous ACTH. The sodium depletion induced by furosemide during continuous ACTH infusion increases plasma renin activity but does not change PA.", "contents": "[Proceedings: Role of endogenous and exogenous ACTH on aldosterone secretion (author's transl)]. The role of ACTH in the control of aldosterone secretion has been investigated in volunteers under a normal sodium diet. Endogenous ACTH suppression by dexamethasone (DXM) does not alter the plasma aldosterone (PA) response to 20 mg furosemide since identical PA increases are observed in control subjects and in subjects with DXM suppressed endogenous ACTH. The sodium depletion induced by furosemide during continuous ACTH infusion increases plasma renin activity but does not change PA."} {"id": "PMID:172009", "title": "Efficacy of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate in therapy of equine abortion virus-induced hepatitis in hamsters.", "content": "Equine abortion virus (EAV)-induced hepatitis in hamsters presents an interesting animal model for the evaluation of drugs possessing anti-deoxyribonucleic acid virus activity. These experiments demonstrate that 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP), a new synthetic, water-soluble, antiviral agent, effectively controls this disease in hamsters with a therapeutic index of approximately 60. Ara-HxMP prevented hepatitis-associated deaths in hamsters, reduced the titer of EAV developing in hamsters, and inhibited the increase of serum glutamic pyruvic transaminase in EAV-infected hamsters.", "contents": "Efficacy of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate in therapy of equine abortion virus-induced hepatitis in hamsters. Equine abortion virus (EAV)-induced hepatitis in hamsters presents an interesting animal model for the evaluation of drugs possessing anti-deoxyribonucleic acid virus activity. These experiments demonstrate that 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP), a new synthetic, water-soluble, antiviral agent, effectively controls this disease in hamsters with a therapeutic index of approximately 60. Ara-HxMP prevented hepatitis-associated deaths in hamsters, reduced the titer of EAV developing in hamsters, and inhibited the increase of serum glutamic pyruvic transaminase in EAV-infected hamsters."} {"id": "PMID:172005", "title": "[Effect of furosemide and ACTH on plasma renin, aldosterone and cortisol levels in normal man].", "content": "Plasma renin activity (PRA), aldosterone and cortisol's variations are studied in normal salt repleted voluntary men (120 mEq/24 h sodium) before and after furosemide infusion and/or constant infusion of ACTH (beta 1-24 corticotrophin). PRA is determined by angiotensin I radioimmunoassay, plasma aldosterone by specific radioimmunoassay and plasma cortisol by competitive transcortine binding radioassay. 1) PRA and plasma aldosterone increase clearly after acute sodium depletion secundary to furosemide infusion; plasma cortisol increases a little. PRA and aldosterone's variations are identical after endogenous ACTH suppression by dexamethazone administration before study. 2) PRA is not influenced by constant infusion (16 ng/kg/mn) after acute infusion (0.3 mg intravenously) of ACTH (beta 1-24); plasma aldosterone and plasma cortisol increase dramatically and remain constant along the experience. 3) If acute sodium depletion is realized 120 mn after ACTH infusion, PRA still raises; on the other hand plasma aldosterone remains constant. These results confirm that acute sodium depletion stimulates aldosterone secretion by the way of renin angiotensin system then ACTH acts directly on the adrenal cortex. Nevertheless the stimulative action of acute sodium depletion on aldosterone secretion is suppressed by previous acute ACTH stimulation.", "contents": "[Effect of furosemide and ACTH on plasma renin, aldosterone and cortisol levels in normal man]. Plasma renin activity (PRA), aldosterone and cortisol's variations are studied in normal salt repleted voluntary men (120 mEq/24 h sodium) before and after furosemide infusion and/or constant infusion of ACTH (beta 1-24 corticotrophin). PRA is determined by angiotensin I radioimmunoassay, plasma aldosterone by specific radioimmunoassay and plasma cortisol by competitive transcortine binding radioassay. 1) PRA and plasma aldosterone increase clearly after acute sodium depletion secundary to furosemide infusion; plasma cortisol increases a little. PRA and aldosterone's variations are identical after endogenous ACTH suppression by dexamethazone administration before study. 2) PRA is not influenced by constant infusion (16 ng/kg/mn) after acute infusion (0.3 mg intravenously) of ACTH (beta 1-24); plasma aldosterone and plasma cortisol increase dramatically and remain constant along the experience. 3) If acute sodium depletion is realized 120 mn after ACTH infusion, PRA still raises; on the other hand plasma aldosterone remains constant. These results confirm that acute sodium depletion stimulates aldosterone secretion by the way of renin angiotensin system then ACTH acts directly on the adrenal cortex. Nevertheless the stimulative action of acute sodium depletion on aldosterone secretion is suppressed by previous acute ACTH stimulation."} {"id": "PMID:172010", "title": "Solid-phase radioimmunoassays for quantitative antibody determination of Clostridium perfringens type D epsilon toxin.", "content": "Two reversed solid-phase radioimmunoassays were developed for quantitative determination of antibodies against Clostridium perfringens type D epsilon toxin. 125I-labeled prototoxin was used in the bromoacetylcellulose-bound antibody method and in the antibody-coated tube method. The antibody values which can be detected by the assays are in the range of 0.004 IU/ml of investigated serum. The methods allow the screening investigation of large groups of vaccinated sheep in a rapid and inexpensive way, and are very suitable for measuring small amounts of C. perfringens D epsilon antibodies with a small experimental error.", "contents": "Solid-phase radioimmunoassays for quantitative antibody determination of Clostridium perfringens type D epsilon toxin. Two reversed solid-phase radioimmunoassays were developed for quantitative determination of antibodies against Clostridium perfringens type D epsilon toxin. 125I-labeled prototoxin was used in the bromoacetylcellulose-bound antibody method and in the antibody-coated tube method. The antibody values which can be detected by the assays are in the range of 0.004 IU/ml of investigated serum. The methods allow the screening investigation of large groups of vaccinated sheep in a rapid and inexpensive way, and are very suitable for measuring small amounts of C. perfringens D epsilon antibodies with a small experimental error."} {"id": "PMID:172011", "title": "Convenient non-chromatographic assays for the microbial deconjugation and 7alpha-OH bioconversion of taurocholate.", "content": "We described two convenient assay methods to estimate bile acid deconjugation and bile acid bioconversion at the 7alpha-OH position by individual microorganisms grown in media containing taurocholic acid. The methods are based on (i) a selective chemical assay for taurine conjugates previously described and (ii) the use of a cell-free preparation of 7alpha-hydroxysteroid dehydrogenase from Escherichia coli to directly quantify 7alpha-OH groups. These non-chromatographic approaches have been applied to the study of three model strains of intestinal organisms, E. coli, Bacteroides fragilis, and Clostridium perfringens, grown in standard media in the presence of purified tritiated taurocholate. Assay results were confirmed by thin-layer chromatography solvent systems designed to separate conjugated from unconjugated bile acid and unmodified cholic acid nucleus from 7alpha-OH bioconversion product(s) (primarily 3alpha, 12alpha dihydroxy, 7-keto-cholanoic acid). In addition, 7alpha-hydroxysteroid dehydrogenase activity was demonstrated in cell-free extracts of all three organisms. Of the three organisms, only C. perfringens was demonstrated to (i) deconjugate taurocholic acid, (ii) contain 3alpha-hydroxysteroid dehydrogenase activity, (iii) convert cholic acid into at least five labeled metabolites visible on thin-layer chromatography, and (iv) catalyze significant tritium exchange with water in the medium.", "contents": "Convenient non-chromatographic assays for the microbial deconjugation and 7alpha-OH bioconversion of taurocholate. We described two convenient assay methods to estimate bile acid deconjugation and bile acid bioconversion at the 7alpha-OH position by individual microorganisms grown in media containing taurocholic acid. The methods are based on (i) a selective chemical assay for taurine conjugates previously described and (ii) the use of a cell-free preparation of 7alpha-hydroxysteroid dehydrogenase from Escherichia coli to directly quantify 7alpha-OH groups. These non-chromatographic approaches have been applied to the study of three model strains of intestinal organisms, E. coli, Bacteroides fragilis, and Clostridium perfringens, grown in standard media in the presence of purified tritiated taurocholate. Assay results were confirmed by thin-layer chromatography solvent systems designed to separate conjugated from unconjugated bile acid and unmodified cholic acid nucleus from 7alpha-OH bioconversion product(s) (primarily 3alpha, 12alpha dihydroxy, 7-keto-cholanoic acid). In addition, 7alpha-hydroxysteroid dehydrogenase activity was demonstrated in cell-free extracts of all three organisms. Of the three organisms, only C. perfringens was demonstrated to (i) deconjugate taurocholic acid, (ii) contain 3alpha-hydroxysteroid dehydrogenase activity, (iii) convert cholic acid into at least five labeled metabolites visible on thin-layer chromatography, and (iv) catalyze significant tritium exchange with water in the medium."} {"id": "PMID:172012", "title": "Studies on the survival and fate of enteroviruses in an experimental model of a municipal solid waste landfill and leachate.", "content": "In laboratory scale municipal solid waste lysimeters containing simulated refuse, and seeded with either laboratory or field strains of poliovirus type 1 and echovirus type 7, viruses were not detected in the lysimeter leachate produced over a 4-month period. In addition, viruses were detected in the lysimeter refuse contents after termination of lysimeter operation. These results appeared to be due to virus retention in the lysimeter caused by virus adsorption and virus inactivation. Evidence for virus inactivation was provided by the results of experiments on virus inactivation in composite leachate samples. Evidence for virus adsorption was supported by the rapid adsorption of viruses to various municipal solid waste components in the presence of a salt similar in composition to the major inorganic salts of leachates.", "contents": "Studies on the survival and fate of enteroviruses in an experimental model of a municipal solid waste landfill and leachate. In laboratory scale municipal solid waste lysimeters containing simulated refuse, and seeded with either laboratory or field strains of poliovirus type 1 and echovirus type 7, viruses were not detected in the lysimeter leachate produced over a 4-month period. In addition, viruses were detected in the lysimeter refuse contents after termination of lysimeter operation. These results appeared to be due to virus retention in the lysimeter caused by virus adsorption and virus inactivation. Evidence for virus inactivation was provided by the results of experiments on virus inactivation in composite leachate samples. Evidence for virus adsorption was supported by the rapid adsorption of viruses to various municipal solid waste components in the presence of a salt similar in composition to the major inorganic salts of leachates."} {"id": "PMID:172006", "title": "[Direct reaction between complement system and cell nuclei (author's transl)].", "content": "A direct in vitro reaction between complement system and cell nuclei of human leucocytes and of cryostat sections of rat liver or kidney, has been demonstrated by an indirect immunofluorescence technique. The first step of this reaction involves a fixation of C1q to the nuclear DNA as shown by the peripheral distribution of the fluorescence and by the extinction of the fluorescence when the tissue-slices are pretreated by DNase but not by RNase or trypsin. This fixation gives rise to an activation of C1 which can be demonstrated by the capacity of the fixed C1 to induce a fixation of C4 of the same distribution. Although the sequential fixation experiments have not allowed to establish directly the fixation of the following components of the complement system (C2 and C3), the positive results obtained using whole fresh normal human serum as a source of complement and a fluorescent anti-human C3 serum clearly indicate that the activation of the classical pathway by whole cells DNA can go as far as the C3 step. All these results were obtained at physiological pH and molarity: this can suggest a physiopathological meaning for this reaction.", "contents": "[Direct reaction between complement system and cell nuclei (author's transl)]. A direct in vitro reaction between complement system and cell nuclei of human leucocytes and of cryostat sections of rat liver or kidney, has been demonstrated by an indirect immunofluorescence technique. The first step of this reaction involves a fixation of C1q to the nuclear DNA as shown by the peripheral distribution of the fluorescence and by the extinction of the fluorescence when the tissue-slices are pretreated by DNase but not by RNase or trypsin. This fixation gives rise to an activation of C1 which can be demonstrated by the capacity of the fixed C1 to induce a fixation of C4 of the same distribution. Although the sequential fixation experiments have not allowed to establish directly the fixation of the following components of the complement system (C2 and C3), the positive results obtained using whole fresh normal human serum as a source of complement and a fluorescent anti-human C3 serum clearly indicate that the activation of the classical pathway by whole cells DNA can go as far as the C3 step. All these results were obtained at physiological pH and molarity: this can suggest a physiopathological meaning for this reaction."} {"id": "PMID:172013", "title": "Enzymatic transformation of morphine by hydroxysteroid dehydrogenase from Pseudomonas testosteroni.", "content": "Eznyme preparations from Pseudomonas testosteroni containing alpha- and beta- hydroxysteroid dehydrogenases catalyzed the oxidation of morphine and codeine by nicotinamide adenine dinucleotide. Morphine was converted in relatively low yield into 14-hydroxymorphinone probably via morphinone as an intermediate. Codeine was converted to codeinone and 14-hydroxycodeinone. Only the conversions at the 6-position were carred out by the hydroxysteroid dehydrogenase. Hydroxylation at the 14-position did occur spontaneously (or enzymatically with a contaminating enzyme) ater oxidation at the 6-position.", "contents": "Enzymatic transformation of morphine by hydroxysteroid dehydrogenase from Pseudomonas testosteroni. Eznyme preparations from Pseudomonas testosteroni containing alpha- and beta- hydroxysteroid dehydrogenases catalyzed the oxidation of morphine and codeine by nicotinamide adenine dinucleotide. Morphine was converted in relatively low yield into 14-hydroxymorphinone probably via morphinone as an intermediate. Codeine was converted to codeinone and 14-hydroxycodeinone. Only the conversions at the 6-position were carred out by the hydroxysteroid dehydrogenase. Hydroxylation at the 14-position did occur spontaneously (or enzymatically with a contaminating enzyme) ater oxidation at the 6-position."} {"id": "PMID:172027", "title": "Milker's nodules. Pathogenesis, tissue culture, electron microscopy, and calf inoculation.", "content": "We report the occurence of milker's nodules in nine patients. In man, the disease goes through maculopapular, target, acute weeping, nodular, papillo-matous, and regressive stages. Papular and papillomatous stages were noted following vaccination of a calf with material prepared from a human lesion. A viral agent was isolated in cultures of bovine kidney cells and human skin fibroblast cells. Cytoplasmic inclusions were frequently seen in the infected bovine kidney cells. Electron microscopy revealed viroplasm, partially encapsulated viroplasm, encapsulated viroplasm, and oval particles with spires around the outside.", "contents": "Milker's nodules. Pathogenesis, tissue culture, electron microscopy, and calf inoculation. We report the occurence of milker's nodules in nine patients. In man, the disease goes through maculopapular, target, acute weeping, nodular, papillo-matous, and regressive stages. Papular and papillomatous stages were noted following vaccination of a calf with material prepared from a human lesion. A viral agent was isolated in cultures of bovine kidney cells and human skin fibroblast cells. Cytoplasmic inclusions were frequently seen in the infected bovine kidney cells. Electron microscopy revealed viroplasm, partially encapsulated viroplasm, encapsulated viroplasm, and oval particles with spires around the outside."} {"id": "PMID:172028", "title": "Ulnar neuropathy after liquid nitrogen cryotherapy.", "content": "Ulnar neuropathy after liquid nitrogen cryotherapy for verruca vulgaris (common wart) overlying the ulnar nerve at the elbow resulted in much disability from sensory and motor deficits.", "contents": "Ulnar neuropathy after liquid nitrogen cryotherapy. Ulnar neuropathy after liquid nitrogen cryotherapy for verruca vulgaris (common wart) overlying the ulnar nerve at the elbow resulted in much disability from sensory and motor deficits."} {"id": "PMID:172029", "title": "Cytomegalovirus-mononucleosis in a newborn infant.", "content": "A 3-week-old infant with haemophilia A developed fever and mononucleosis and was found to have cytomegalovirus, infection, possibly acquired by blood transfusion. At 6 months, while still excreting cytomgalovirus, he developed transient clinical jaundice with a hepatitis-like picture.", "contents": "Cytomegalovirus-mononucleosis in a newborn infant. A 3-week-old infant with haemophilia A developed fever and mononucleosis and was found to have cytomegalovirus, infection, possibly acquired by blood transfusion. At 6 months, while still excreting cytomgalovirus, he developed transient clinical jaundice with a hepatitis-like picture."} {"id": "PMID:172030", "title": "Epidermal neoplasms with epidermolysis bullosa dystrophica with the first report of carcinoma with the acquired type.", "content": "Carcinoma, usually always squamous cell carcinoma, is one of the most serious complications in epidermolysis bullosa dystrophica. It can occur on the skin, mucous membranes, the esophagus and possibly the upper part of the bronchial tree. We are reporting on four new patients; one, the youngest to be so reported, one with a definite autosomal dominant inheritance and one with a chronic acquired dystrophica epidermolysis bullosa. Most cases have an autosomal recessive inheritance, but the disorder is probably more hetereogeneous in its inheritance than has been reported. Studies of the collagen indicate a disturbance, but present studies indicate the defect to be more a cellular defect in the fibroblast yet undetermined. The carcinomas, usually multiple, appear to arise on scarred tissue and to metastasize rapidly with death.", "contents": "Epidermal neoplasms with epidermolysis bullosa dystrophica with the first report of carcinoma with the acquired type. Carcinoma, usually always squamous cell carcinoma, is one of the most serious complications in epidermolysis bullosa dystrophica. It can occur on the skin, mucous membranes, the esophagus and possibly the upper part of the bronchial tree. We are reporting on four new patients; one, the youngest to be so reported, one with a definite autosomal dominant inheritance and one with a chronic acquired dystrophica epidermolysis bullosa. Most cases have an autosomal recessive inheritance, but the disorder is probably more hetereogeneous in its inheritance than has been reported. Studies of the collagen indicate a disturbance, but present studies indicate the defect to be more a cellular defect in the fibroblast yet undetermined. The carcinomas, usually multiple, appear to arise on scarred tissue and to metastasize rapidly with death."} {"id": "PMID:172031", "title": "Studies on the role of C-type viruses in the development of epithelial tumors induced with DMBA.", "content": "Epithelial tumors were induced using 0.5 per cent solution of DMBA in two strains of mice--one infected with leukoviruses (Swiss mice), and the other is free of these viruses (hairless mice). Tumors from 15 mice of each strain were examined light- and electron-microscopically. Depending on the period of administration of the carcinogen, benign growths of the type of papilloma or keratoacanthoma were obtained, or malignant tumors. In the tumors in Swiss mice electron microscopy revealed a distinct increase in the numbers of viruses in comparison with surrounding skin and intact skin of healthy mice of this strain. In spite of certain histologic differences between tumors produced in Swiss and hairless mice, the results argue against a role of leukoviruses in the pathogenesis of experimentally induced epithelial tumors in mice.", "contents": "Studies on the role of C-type viruses in the development of epithelial tumors induced with DMBA. Epithelial tumors were induced using 0.5 per cent solution of DMBA in two strains of mice--one infected with leukoviruses (Swiss mice), and the other is free of these viruses (hairless mice). Tumors from 15 mice of each strain were examined light- and electron-microscopically. Depending on the period of administration of the carcinogen, benign growths of the type of papilloma or keratoacanthoma were obtained, or malignant tumors. In the tumors in Swiss mice electron microscopy revealed a distinct increase in the numbers of viruses in comparison with surrounding skin and intact skin of healthy mice of this strain. In spite of certain histologic differences between tumors produced in Swiss and hairless mice, the results argue against a role of leukoviruses in the pathogenesis of experimentally induced epithelial tumors in mice."} {"id": "PMID:172032", "title": "Desmosome-like structures in the cytoplasm of normal human keratinocyte.", "content": "Desmosome-like structures in the cytoplasm which have so far been described in tumoral and acantholytic epidermal cells were observed on two occasions in morphologically normal basal and prickle cells. It seems that under specific conditions a normal epidermal cell can lose contact with the surrounding cell during cell division and forms intracytoplasmic desmosomes.", "contents": "Desmosome-like structures in the cytoplasm of normal human keratinocyte. Desmosome-like structures in the cytoplasm which have so far been described in tumoral and acantholytic epidermal cells were observed on two occasions in morphologically normal basal and prickle cells. It seems that under specific conditions a normal epidermal cell can lose contact with the surrounding cell during cell division and forms intracytoplasmic desmosomes."} {"id": "PMID:172033", "title": "In vitro action of quartz on alveolar macrophage lipid peroxides.", "content": "The in vitro effects of quartz particles on the lipid peroxide rate were measured on guinea pig pulmonary alveolar macrophages (PAMs). As controls, either PAMs alone or exposed to inert dust were used. The amount of lipid peroxide resulting after one-hour incubation was determined by means of the thiobarbituric acid test (TBA). The results showed that quartz induced a substantial increase of lipid peroxide in PAMs compared with both samples (dust-free or exposed to corundum). The influence of pretreatment of quartz by polyvinylpyridine-N-oxide (PVPNO) and by mineral water containing carbonate and chloride ions was also studied.", "contents": "In vitro action of quartz on alveolar macrophage lipid peroxides. The in vitro effects of quartz particles on the lipid peroxide rate were measured on guinea pig pulmonary alveolar macrophages (PAMs). As controls, either PAMs alone or exposed to inert dust were used. The amount of lipid peroxide resulting after one-hour incubation was determined by means of the thiobarbituric acid test (TBA). The results showed that quartz induced a substantial increase of lipid peroxide in PAMs compared with both samples (dust-free or exposed to corundum). The influence of pretreatment of quartz by polyvinylpyridine-N-oxide (PVPNO) and by mineral water containing carbonate and chloride ions was also studied."} {"id": "PMID:172034", "title": "Adenyl cyclase.", "content": "Many hormones interact with their target cells by binding to receptors located on the external surface of the target cells' plasma membrane and subsequently stimulating the enzyme, adenyl cyclase, which is located within the plasma membrane. Stimulation of adenyl cyclase results in formation of cyclic AMP which is released from the membrane into the cell and acts within the cell to regulate a wide variety of cellular processes. In this review, the characteristics of hormone receptors and the relationship between receptor occupancy and adenyl cyclase stimulation are discussed. Our current understanding of the roles of hormones, substrate, magnesium, calcium, and guanine nucleotides as regulators of adenyl cyclase activity is summarized. Because of the central importance of adenyl cyclase and cyclic AMP as mediators of the cellular response to hormones, it is to be expected that many diseases may result from defects in this enzyme system. Indeed, several adenyl cyclase related diseases have been identified and the molecular bases for these diseases are discussed in this review.", "contents": "Adenyl cyclase. Many hormones interact with their target cells by binding to receptors located on the external surface of the target cells' plasma membrane and subsequently stimulating the enzyme, adenyl cyclase, which is located within the plasma membrane. Stimulation of adenyl cyclase results in formation of cyclic AMP which is released from the membrane into the cell and acts within the cell to regulate a wide variety of cellular processes. In this review, the characteristics of hormone receptors and the relationship between receptor occupancy and adenyl cyclase stimulation are discussed. Our current understanding of the roles of hormones, substrate, magnesium, calcium, and guanine nucleotides as regulators of adenyl cyclase activity is summarized. Because of the central importance of adenyl cyclase and cyclic AMP as mediators of the cellular response to hormones, it is to be expected that many diseases may result from defects in this enzyme system. Indeed, several adenyl cyclase related diseases have been identified and the molecular bases for these diseases are discussed in this review."} {"id": "PMID:172035", "title": "Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma.", "content": "In the completed adjuvant chemotherapy lung trials conducted by the Veterans Administration Surgical Group, the cell type was recorded in 2,341 of 2,349 curative resections; extent of lymph node involvement was known in all cases. Nodes were normal in 1,231 patients. Five- and ten-year survival computed by the life-table method was 33.7% and 20.4%, respectively. These rates were significantly greater than the 16.2% and 8.8% recorded in 1,118 patients whose nodes showed metastases. Among patients whose cell type was known, five-year survival in 484 with hilar node involvement was 17.4% and was not significantly different from 20.1% in 364 patients in whom only lobar nodes were involved. The survival was 8.9% in 268 patients with cancer in the mediastinal nodes; this was significantly worse than either of the aforementioned groups. A five-year survival of 26.8% in 1,482 patients with squamous cell carcinoma was greater than the 24.3% in 359 with adenocarcinoma and 22.4% in 500 with undifferentiated cell types, but the differences were not significant. Variations between these groups remained nonsignificant when nodes were normal and were of only borderline significance, at the 5% level, when they showed metastasis. When a curative resection has been accomplished, cell-type as classified in this study has little bearing on long-term survival, whereas the presence of node metastasis as well as its location is of the utmost importance.", "contents": "Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma. In the completed adjuvant chemotherapy lung trials conducted by the Veterans Administration Surgical Group, the cell type was recorded in 2,341 of 2,349 curative resections; extent of lymph node involvement was known in all cases. Nodes were normal in 1,231 patients. Five- and ten-year survival computed by the life-table method was 33.7% and 20.4%, respectively. These rates were significantly greater than the 16.2% and 8.8% recorded in 1,118 patients whose nodes showed metastases. Among patients whose cell type was known, five-year survival in 484 with hilar node involvement was 17.4% and was not significantly different from 20.1% in 364 patients in whom only lobar nodes were involved. The survival was 8.9% in 268 patients with cancer in the mediastinal nodes; this was significantly worse than either of the aforementioned groups. A five-year survival of 26.8% in 1,482 patients with squamous cell carcinoma was greater than the 24.3% in 359 with adenocarcinoma and 22.4% in 500 with undifferentiated cell types, but the differences were not significant. Variations between these groups remained nonsignificant when nodes were normal and were of only borderline significance, at the 5% level, when they showed metastasis. When a curative resection has been accomplished, cell-type as classified in this study has little bearing on long-term survival, whereas the presence of node metastasis as well as its location is of the utmost importance."} {"id": "PMID:172036", "title": "Effects of phentolamine on dibutyryl cyclic AMP and norepinephrine in rats anesthetized with amobarbital.", "content": "In vitro evidence demonstrated that norepinephrine (NE) increased endogenous levels of cyclic AMP in brain tissue. In vivo findings showed that in rats anesthetized with amobarbital, NE certrally administered prolonged narcosis whereas exogenous dibutyryl cyclic AMP shortened it. Phentolamine, an alpha adrenergic receptor inhibitor, administered centrally prolonged narcosis but did block all symptomatology accompanying its administration. Phentolamine added to dibutyryl cyclic AMP dose-relatedly antagonized the shortening of the duration of narcosis. Such ovservations suggest that whereas the inhibitory action of phentolamine affects NE at the alpha adrenergic receptor site, it antagonizes cyclic AMP at other sites as well.", "contents": "Effects of phentolamine on dibutyryl cyclic AMP and norepinephrine in rats anesthetized with amobarbital. In vitro evidence demonstrated that norepinephrine (NE) increased endogenous levels of cyclic AMP in brain tissue. In vivo findings showed that in rats anesthetized with amobarbital, NE certrally administered prolonged narcosis whereas exogenous dibutyryl cyclic AMP shortened it. Phentolamine, an alpha adrenergic receptor inhibitor, administered centrally prolonged narcosis but did block all symptomatology accompanying its administration. Phentolamine added to dibutyryl cyclic AMP dose-relatedly antagonized the shortening of the duration of narcosis. Such ovservations suggest that whereas the inhibitory action of phentolamine affects NE at the alpha adrenergic receptor site, it antagonizes cyclic AMP at other sites as well."} {"id": "PMID:172037", "title": "In vivo pulmonary metabolism of bradykinin, angiotensin I and 5-hydroxtryptamine in the rat.", "content": "Involvement of the pulmonary vasculature of the rat in the in vivo metabolism of bradykinin, angiotensin I and 5-hydroxytryptamine was studied by monitoring the systemic blood pressure response of the test animal during intravenous or intraarterial administration of these substances. Observation of essentially the same blood pressure response regardless of the route of injection indicated that neither agiotensins I or II nor 5-hydroxytryptamine was metabolized by the pulmonary vasculature, while bradykinin was inactivated to the extent of 95+% on one passage through the lung. In the rat the major portion of bradykinin inactivation and angiotensin conversion apparently occur at different places in the vascular tree and therefore could not be carried out by the same enzyme. Differential inhibition by 2-mercaptoethanol and the bradykinin potentiating peptide, Pyr-Lys-Trp-Ala-Pro, support this postulate. One rat was found which had no pulmonary kininase but could convert angiotensin I to angiotensin II. In addition, infusion of large doses of known inhibitors of lung converting enzyme had no effect on either angiotensin I conversion or bradykinin inactivation in this system. These results support the idea that the pulmonary vasculature is not a major site for conversion of angiotensin I in the rat.", "contents": "In vivo pulmonary metabolism of bradykinin, angiotensin I and 5-hydroxtryptamine in the rat. Involvement of the pulmonary vasculature of the rat in the in vivo metabolism of bradykinin, angiotensin I and 5-hydroxytryptamine was studied by monitoring the systemic blood pressure response of the test animal during intravenous or intraarterial administration of these substances. Observation of essentially the same blood pressure response regardless of the route of injection indicated that neither agiotensins I or II nor 5-hydroxytryptamine was metabolized by the pulmonary vasculature, while bradykinin was inactivated to the extent of 95+% on one passage through the lung. In the rat the major portion of bradykinin inactivation and angiotensin conversion apparently occur at different places in the vascular tree and therefore could not be carried out by the same enzyme. Differential inhibition by 2-mercaptoethanol and the bradykinin potentiating peptide, Pyr-Lys-Trp-Ala-Pro, support this postulate. One rat was found which had no pulmonary kininase but could convert angiotensin I to angiotensin II. In addition, infusion of large doses of known inhibitors of lung converting enzyme had no effect on either angiotensin I conversion or bradykinin inactivation in this system. These results support the idea that the pulmonary vasculature is not a major site for conversion of angiotensin I in the rat."} {"id": "PMID:172038", "title": "Lack of steroidogenic response to cyclic AMP and ACTH in adrenal cells from rats bearing the MtTF4 tumor.", "content": "Adrenal cell suspensions prepared from rats bearing the MtTF4 tumor failed to increase corticosterone production when exposed to adenosine 3', 5'-cyclic monophosphate (cyclic AMP) or ACTH, placing the defect in these adrenals beyond the ACTH receptor site. Adrenal cells from normal rats responded well to these stimuli. Adrenal cyclic AMP phosphodiesterase prepared from the tumor bearing rats appeared normal both with respect to its specific activity and inhibition profile with theophylline. Exposure of the MtTF4 adrenal cells to 1,2-3H-cholesterol in the presence of either cyclic AMP or ACTH did not result in an increase in radioactively labeled corticosterone, whereas increased label could be demonstrated in adrenal cells from normal rats similarly treated.", "contents": "Lack of steroidogenic response to cyclic AMP and ACTH in adrenal cells from rats bearing the MtTF4 tumor. Adrenal cell suspensions prepared from rats bearing the MtTF4 tumor failed to increase corticosterone production when exposed to adenosine 3', 5'-cyclic monophosphate (cyclic AMP) or ACTH, placing the defect in these adrenals beyond the ACTH receptor site. Adrenal cells from normal rats responded well to these stimuli. Adrenal cyclic AMP phosphodiesterase prepared from the tumor bearing rats appeared normal both with respect to its specific activity and inhibition profile with theophylline. Exposure of the MtTF4 adrenal cells to 1,2-3H-cholesterol in the presence of either cyclic AMP or ACTH did not result in an increase in radioactively labeled corticosterone, whereas increased label could be demonstrated in adrenal cells from normal rats similarly treated."} {"id": "PMID:172039", "title": "[Suitability of immune serums from different animal species for the preparation of conjugates against Aujeszky's disease virus].", "content": "A comparison was made of immune serum from rabbits, sheeps, pigs and cattle. Pure IgG was prepared by the Rivanol sulphate method and immune electrophoresis. Optimum protein quality, conjugation time under various conditions and using two preparations of fluorescein isothiocyanate were studied. Conjugate purified by DEAE-Sephadex A-50 and concentrated to 1% protein by ultrafiltration was freeze-dried and then tested for activity and the degree of non-specific fluorescence. Evaluation by yield of immuno-electrophoretically pure IgG, conjugation time, antibody content, degree of non-specific fluorescence and the intensity of specific fluorescence before and after dilution showed that pig serum was the best, followed by cattle and sheep serum; rabbit serum was the least suitable for conjugate preparation.", "contents": "[Suitability of immune serums from different animal species for the preparation of conjugates against Aujeszky's disease virus]. A comparison was made of immune serum from rabbits, sheeps, pigs and cattle. Pure IgG was prepared by the Rivanol sulphate method and immune electrophoresis. Optimum protein quality, conjugation time under various conditions and using two preparations of fluorescein isothiocyanate were studied. Conjugate purified by DEAE-Sephadex A-50 and concentrated to 1% protein by ultrafiltration was freeze-dried and then tested for activity and the degree of non-specific fluorescence. Evaluation by yield of immuno-electrophoretically pure IgG, conjugation time, antibody content, degree of non-specific fluorescence and the intensity of specific fluorescence before and after dilution showed that pig serum was the best, followed by cattle and sheep serum; rabbit serum was the least suitable for conjugate preparation."} {"id": "PMID:172040", "title": "The immunological response of calves after submucosal application of a live vaccine against parainfluenza-3- and adenovirus. (Brief report).", "content": "Using submucosal application of live attenuated vaccine against parainfluenza-3-virus and cattle adenovirus within the nasal opening, calves reacted with the formation of secretory (local) and serum antibodies of significantly higher titers than are received using subcutaneous application. The same vaccine induces interferon activity in the serum and nasal secretion after submucosal vaccination. Adenovirus antigen is a stronger interferon inducer than para-influenza-3-virus.", "contents": "The immunological response of calves after submucosal application of a live vaccine against parainfluenza-3- and adenovirus. (Brief report). Using submucosal application of live attenuated vaccine against parainfluenza-3-virus and cattle adenovirus within the nasal opening, calves reacted with the formation of secretory (local) and serum antibodies of significantly higher titers than are received using subcutaneous application. The same vaccine induces interferon activity in the serum and nasal secretion after submucosal vaccination. Adenovirus antigen is a stronger interferon inducer than para-influenza-3-virus."} {"id": "PMID:172041", "title": "[Electron microscopy studies on proliferation of foot-and-mouth disease virus in cell cultures. I. Morphologic changes in cell nucleus].", "content": "The first morphological indication of FMD infection of a cell culture was in the nucleus. Components of nucleoli became segregated and were finally present only as remnants. It was not possible to distinguish different stages of segregation, as in the case of entero-virus infections, because of the rapidity of FMD virus proliferation. Following changes in nucleoli there was margination of chromatin. Particularly striking was an increase in interchromatin granules. Changes in the nuclear membrane seemed to facilitate the transfer of nuclear material to the cytoplasm. Strongly pronounced dilatation of the peri-nuclear cleft, like that seen in aphthae and other tissues, were rarely visible in infected cell cultures.", "contents": "[Electron microscopy studies on proliferation of foot-and-mouth disease virus in cell cultures. I. Morphologic changes in cell nucleus]. The first morphological indication of FMD infection of a cell culture was in the nucleus. Components of nucleoli became segregated and were finally present only as remnants. It was not possible to distinguish different stages of segregation, as in the case of entero-virus infections, because of the rapidity of FMD virus proliferation. Following changes in nucleoli there was margination of chromatin. Particularly striking was an increase in interchromatin granules. Changes in the nuclear membrane seemed to facilitate the transfer of nuclear material to the cytoplasm. Strongly pronounced dilatation of the peri-nuclear cleft, like that seen in aphthae and other tissues, were rarely visible in infected cell cultures."} {"id": "PMID:172042", "title": "[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. II. Changes in nucleic acid metabolism of the cell nucleus].", "content": "BHK cells were infected with FMD virus and treated with tritium-labelled thymidine and uridine for examination by autoradiography under the electron microscope. Labelling of the DNA, examined by autoradiography under the optical microscope, showed inhibition of 3H-thymidine incorporation. For demonstrating RNA labelling of nuclei, some cells were treated with actinomycin D and others were left untreated. Under the lectron microscope there was no evidence of increased 3H-uridine incorporation in the untreated cells after virus infection, but actinomycin treatment increased RNA labelling in extranucleolar parts of the nucleus, evidently RNA synthesis independent of DNA. There was evidence of some synthesis of virus-specific RNA in the nuclei. The extent of virus-specific RNA synthesis in the cytoplasm was less extensive than in the nucleus.", "contents": "[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. II. Changes in nucleic acid metabolism of the cell nucleus]. BHK cells were infected with FMD virus and treated with tritium-labelled thymidine and uridine for examination by autoradiography under the electron microscope. Labelling of the DNA, examined by autoradiography under the optical microscope, showed inhibition of 3H-thymidine incorporation. For demonstrating RNA labelling of nuclei, some cells were treated with actinomycin D and others were left untreated. Under the lectron microscope there was no evidence of increased 3H-uridine incorporation in the untreated cells after virus infection, but actinomycin treatment increased RNA labelling in extranucleolar parts of the nucleus, evidently RNA synthesis independent of DNA. There was evidence of some synthesis of virus-specific RNA in the nuclei. The extent of virus-specific RNA synthesis in the cytoplasm was less extensive than in the nucleus."} {"id": "PMID:172043", "title": "[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. III. Morphogenesis in cytoplasm].", "content": "The previous parts have been concerned with the participation of the cell nucleus in the formation of the RNA of FMD virus. However, the actual morphogenesis of the virus takes place in cytoplasm. In BHK cells, changes attributable to virus infection were visible by the second hour, with the formation of threads and large polysome complexes near the nucleus. Viral particles soon appeared between these structures. There were no pronounced foci of viroplasma, and it seemed that they were not necessary. Simultaneously new membranes formed in the cell. Clumps of viral particles were next visible in the cxtoplasma. The clumps became enveloped and were transported in this way to the periphery of the cell. Elsewhere there was uptake of particles in autophagic vacuoles, an expression of cellular defensive processes. In ultra-thin sections the virions measured 21-25 nm. Within vacuoles the inner part of the virus, the nucleoid, showed greater contrast than the periphery, the capsid. At first there were only slight changes in mitochondria. Liberation of virus by cell rupture occurred only after severe damage to the cell, particularly the lysosome membranes.", "contents": "[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. III. Morphogenesis in cytoplasm]. The previous parts have been concerned with the participation of the cell nucleus in the formation of the RNA of FMD virus. However, the actual morphogenesis of the virus takes place in cytoplasm. In BHK cells, changes attributable to virus infection were visible by the second hour, with the formation of threads and large polysome complexes near the nucleus. Viral particles soon appeared between these structures. There were no pronounced foci of viroplasma, and it seemed that they were not necessary. Simultaneously new membranes formed in the cell. Clumps of viral particles were next visible in the cxtoplasma. The clumps became enveloped and were transported in this way to the periphery of the cell. Elsewhere there was uptake of particles in autophagic vacuoles, an expression of cellular defensive processes. In ultra-thin sections the virions measured 21-25 nm. Within vacuoles the inner part of the virus, the nucleoid, showed greater contrast than the periphery, the capsid. At first there were only slight changes in mitochondria. Liberation of virus by cell rupture occurred only after severe damage to the cell, particularly the lysosome membranes."} {"id": "PMID:172044", "title": "[Enzyme activity in cell cultures infected with herpesvirus suis].", "content": "The activity of succinate dehydrogenase (SDH) and lactage dehydrogenase (LDH) was studied in chick-embryo fibroblast cultures after inoculation of the virulent strain \"A2\" and the avirulent strain \"MK\" of herpesvirus suum. Strain \"A2\" reduced SDH activity, and so did strain MK, but here the decrease of enzyme activity was slower, and it did not become evident until the 24th hour. LDH activity fluctuated after \"A2\" infection but was generally increased, while there was no change in LDH activity, compared with uninfected control cells, after \"MK\" infection. When interaction of cell and virus took place in the presence of 5-iodo-2-desoxyuridine (IUDR), strain \"A2\" produced little change in the enzymes, but \"MK\" infection was accompanied by a definite fall in SDH and a slight increase in LDH. The presence of IUDR inhibited the proliferation of the virulent strain but had no apparent effect on proliferation of the attenuated strain \"MK\". Investigation of the enzyme activity of cells infected with Aujeszky's disease virus has revealed new biological properties of the virus, which might serve to distinguish between different strains of the virus.", "contents": "[Enzyme activity in cell cultures infected with herpesvirus suis]. The activity of succinate dehydrogenase (SDH) and lactage dehydrogenase (LDH) was studied in chick-embryo fibroblast cultures after inoculation of the virulent strain \"A2\" and the avirulent strain \"MK\" of herpesvirus suum. Strain \"A2\" reduced SDH activity, and so did strain MK, but here the decrease of enzyme activity was slower, and it did not become evident until the 24th hour. LDH activity fluctuated after \"A2\" infection but was generally increased, while there was no change in LDH activity, compared with uninfected control cells, after \"MK\" infection. When interaction of cell and virus took place in the presence of 5-iodo-2-desoxyuridine (IUDR), strain \"A2\" produced little change in the enzymes, but \"MK\" infection was accompanied by a definite fall in SDH and a slight increase in LDH. The presence of IUDR inhibited the proliferation of the virulent strain but had no apparent effect on proliferation of the attenuated strain \"MK\". Investigation of the enzyme activity of cells infected with Aujeszky's disease virus has revealed new biological properties of the virus, which might serve to distinguish between different strains of the virus."} {"id": "PMID:172045", "title": "[The mutagenic effect of methyl methanesulfonate (MMS) in vitro and in the host-mediated assay (author's transl)].", "content": "The concentration- and time-dependent genetic activity of methyl methanesulfonate (MMS) was investigated in vitro and in the host-mediated assay using four different indicator organisms. Dose/effect curves achieved with the different indicator organisms are similar.", "contents": "[The mutagenic effect of methyl methanesulfonate (MMS) in vitro and in the host-mediated assay (author's transl)]. The concentration- and time-dependent genetic activity of methyl methanesulfonate (MMS) was investigated in vitro and in the host-mediated assay using four different indicator organisms. Dose/effect curves achieved with the different indicator organisms are similar."} {"id": "PMID:172046", "title": "[Histochemical study of the enzymes of glycogen metabolism in the human endometrium during the normal menstrual cycle].", "content": "The content of glycogen in the human endometrium is dependet on the activity of enzymes involved in processes of synthesis and dissociation of glicogen: glycogen-synthetase, phosphorilase and glycogen-6-phosphatase. The activation of \"D\" form of glycogensynthetase dependent on glucose-6-phosphate and the increase of the glycoogen quantity in the endometrium glands epithelium is observed in the period of growing gestagenic function of the ovaries. At the end of the secretory phase there occurs activation of the glycogen dissociation enzme-phosphorilase which goes in parallel with abrupt inhibition of the glycogensynthetase activity and disappearance or glycogen from the gland epithelium. The inhibition of glycogen synthetase is conditioned by a decreased level of intracellular glucose-6-phosphate which appears due to activation of glucose-6-phosphate in this period.", "contents": "[Histochemical study of the enzymes of glycogen metabolism in the human endometrium during the normal menstrual cycle]. The content of glycogen in the human endometrium is dependet on the activity of enzymes involved in processes of synthesis and dissociation of glicogen: glycogen-synthetase, phosphorilase and glycogen-6-phosphatase. The activation of \"D\" form of glycogensynthetase dependent on glucose-6-phosphate and the increase of the glycoogen quantity in the endometrium glands epithelium is observed in the period of growing gestagenic function of the ovaries. At the end of the secretory phase there occurs activation of the glycogen dissociation enzme-phosphorilase which goes in parallel with abrupt inhibition of the glycogensynthetase activity and disappearance or glycogen from the gland epithelium. The inhibition of glycogen synthetase is conditioned by a decreased level of intracellular glucose-6-phosphate which appears due to activation of glucose-6-phosphate in this period."} {"id": "PMID:172047", "title": "[Effect of physical work on the aging process in certain skeletal bones of the extremities].", "content": "The long-term investigation of the influence of physical exercise upon the structure of human skeleton revealed certain peculiar features in the process of developmental reconstruction of joints of the upper (humeral joint, hand joints) and lower (knee joint, the joints of the foot) extremities resulting from the occupation of the persons under study. Roentgen-anatomical studies performed in 433 industrial and 430 office workers established the fact of retardation and deceleration of ageing of the extremities bone system in representatives of physical labour as compared with office workers. So the significance of spectal physical exercises compensating the progressing with age hypodynamia in persons of non-physical labour gets special importance.", "contents": "[Effect of physical work on the aging process in certain skeletal bones of the extremities]. The long-term investigation of the influence of physical exercise upon the structure of human skeleton revealed certain peculiar features in the process of developmental reconstruction of joints of the upper (humeral joint, hand joints) and lower (knee joint, the joints of the foot) extremities resulting from the occupation of the persons under study. Roentgen-anatomical studies performed in 433 industrial and 430 office workers established the fact of retardation and deceleration of ageing of the extremities bone system in representatives of physical labour as compared with office workers. So the significance of spectal physical exercises compensating the progressing with age hypodynamia in persons of non-physical labour gets special importance."} {"id": "PMID:172048", "title": "[Types of the secretory cells in the pancreatic islands of some vertebrates].", "content": "Three types of secretory cells -- B, A and D were found in the pancreatic islets of the frog, turtle, crucian, rat and cat by the method of electron microscopy. The fine structure of secretory granules is a basis for identification of the endocrine cell types. The structure of the insuline granules is changed more markedly in the evolution process while the granules of A and D cells have a similar structure in the vertebrates under study.", "contents": "[Types of the secretory cells in the pancreatic islands of some vertebrates]. Three types of secretory cells -- B, A and D were found in the pancreatic islets of the frog, turtle, crucian, rat and cat by the method of electron microscopy. The fine structure of secretory granules is a basis for identification of the endocrine cell types. The structure of the insuline granules is changed more markedly in the evolution process while the granules of A and D cells have a similar structure in the vertebrates under study."} {"id": "PMID:172049", "title": "[Electrophysiology in neuropathy caused by vincristine].", "content": "Ten patients treated with vincristine were submitted for electrophysiological examination. It was investigated the number of motor units within the thenar muscle following a technique described previously (Sica et al. - 1974); motor and sensitive conduction velocities as well as motor distal latencies in the median nerve were studied following conventional techniques. The behaviour of the evoked muscle potential with repetitive supramaximal stimulation over the median nerve was also investigated. The findings were compared with control groups. The estimated number of motor units was disminished in eight of ten patients and the average number was significantly different from the control group (control 318 +/- 71 UM; patients 174 +/- 84 UM; P less than 0.001). The potential amplitudes in most of the surviving units were reduced, others remaining within the normal range. This makes apparent that the peripherical nervous system fails to compensate adequately and, furthermore, a loss of individual muscle fibres occurs within some individual units. The conduction velocities of the fastest conducting motor nerve fibres were reduced and motor distal latencies prolongued (Table 1). Maximal impulse conduction velocities were measured in sensory fibres. In 5 of 7 subjets investigated the values laied just beyond the lower limit of the normal range. The amplitude of the sensory orthodromic evoked potential in the median nerve at the wrist was disminished almost in the whole group. The decremental muscle response to repetitive nerve stimulation, can be interpreted as the result of the damage at the neural apparatus at the motor end plate; it was observed in 57% of the patients. In summary, evidences have been registered showing that the nervous supply to the muscle is affected in patients treated with vincristine; the motor unit behaviour under this conditions is discussed.", "contents": "[Electrophysiology in neuropathy caused by vincristine]. Ten patients treated with vincristine were submitted for electrophysiological examination. It was investigated the number of motor units within the thenar muscle following a technique described previously (Sica et al. - 1974); motor and sensitive conduction velocities as well as motor distal latencies in the median nerve were studied following conventional techniques. The behaviour of the evoked muscle potential with repetitive supramaximal stimulation over the median nerve was also investigated. The findings were compared with control groups. The estimated number of motor units was disminished in eight of ten patients and the average number was significantly different from the control group (control 318 +/- 71 UM; patients 174 +/- 84 UM; P less than 0.001). The potential amplitudes in most of the surviving units were reduced, others remaining within the normal range. This makes apparent that the peripherical nervous system fails to compensate adequately and, furthermore, a loss of individual muscle fibres occurs within some individual units. The conduction velocities of the fastest conducting motor nerve fibres were reduced and motor distal latencies prolongued (Table 1). Maximal impulse conduction velocities were measured in sensory fibres. In 5 of 7 subjets investigated the values laied just beyond the lower limit of the normal range. The amplitude of the sensory orthodromic evoked potential in the median nerve at the wrist was disminished almost in the whole group. The decremental muscle response to repetitive nerve stimulation, can be interpreted as the result of the damage at the neural apparatus at the motor end plate; it was observed in 57% of the patients. In summary, evidences have been registered showing that the nervous supply to the muscle is affected in patients treated with vincristine; the motor unit behaviour under this conditions is discussed."} {"id": "PMID:172050", "title": "Acute ocular infection by type 2 herpes simplex virus in adults.", "content": "Acute ocular infections in two adults were caused by type 2 herpes simplex virus (HSV) (\"genital herpesvirus\"). One patient had an acute blepharoconjunctivitis, the other an acute keratoconjunctivitis. Genital infections had preceded the eye infections, and type 2 HSV was isolated from the eyes of both patients and from the genital lesions of one patient. This strongly suggests transmission of type 2 HSV from the genital site to the eye.", "contents": "Acute ocular infection by type 2 herpes simplex virus in adults. Acute ocular infections in two adults were caused by type 2 herpes simplex virus (HSV) (\"genital herpesvirus\"). One patient had an acute blepharoconjunctivitis, the other an acute keratoconjunctivitis. Genital infections had preceded the eye infections, and type 2 HSV was isolated from the eyes of both patients and from the genital lesions of one patient. This strongly suggests transmission of type 2 HSV from the genital site to the eye."} {"id": "PMID:172051", "title": "Oat cell carcinoma of the bronchus and the carcinoid syndrome.", "content": "A man with high urinary levels of 5-hydroxyindole acetic acid had an oat cell carcinoma of the bronchus. The patient had symptoms of the carcinoid syndrome and at autopsy was found to have evidence of carcinoid heart disease. This report supports the hypothesis that bronchial carcinoids and oat cell carcinomas are derived from argentaffin (Kulchitsky)-type cells of the lung.", "contents": "Oat cell carcinoma of the bronchus and the carcinoid syndrome. A man with high urinary levels of 5-hydroxyindole acetic acid had an oat cell carcinoma of the bronchus. The patient had symptoms of the carcinoid syndrome and at autopsy was found to have evidence of carcinoid heart disease. This report supports the hypothesis that bronchial carcinoids and oat cell carcinomas are derived from argentaffin (Kulchitsky)-type cells of the lung."} {"id": "PMID:172052", "title": "Endocrine-type granules in cells of glomus tumor of the stomach.", "content": "The ultrastructure of a gastric glomus tumor was studied. The tumor cells were found to possess structural features similar to those of smooth muscle cells. In addition, hitherto undescribed granules of endocrine type and cilia were identified.", "contents": "Endocrine-type granules in cells of glomus tumor of the stomach. The ultrastructure of a gastric glomus tumor was studied. The tumor cells were found to possess structural features similar to those of smooth muscle cells. In addition, hitherto undescribed granules of endocrine type and cilia were identified."} {"id": "PMID:172053", "title": "Primary adenocarcinoma of the appendix. A clinicopathological study of 11 cases.", "content": "Of eleven cases of adenocarcinoma of the appendix that were studied, five were examples of mucinous cystadenocarcinoma and four were examples of colonic-type adenocarcinoma. Two lesions were very distinctive, with thick, cord-like transformation of the appendix. The term linitis plastica carcinoma is proposed to describe this rare variant of appendiceal carcinoma. Justification for the separation of linitis plastica carcinoma from the other two types is based on morphological appearance and on outcome. Both our linitis plastica patients died of metastases within six months of surgery, whereas, in the other two groups, death was directly related to spread of the carcinoma in only two of nine patients.", "contents": "Primary adenocarcinoma of the appendix. A clinicopathological study of 11 cases. Of eleven cases of adenocarcinoma of the appendix that were studied, five were examples of mucinous cystadenocarcinoma and four were examples of colonic-type adenocarcinoma. Two lesions were very distinctive, with thick, cord-like transformation of the appendix. The term linitis plastica carcinoma is proposed to describe this rare variant of appendiceal carcinoma. Justification for the separation of linitis plastica carcinoma from the other two types is based on morphological appearance and on outcome. Both our linitis plastica patients died of metastases within six months of surgery, whereas, in the other two groups, death was directly related to spread of the carcinoma in only two of nine patients."} {"id": "PMID:172055", "title": "The effect of natural and artificial breeding using bulls infected with, or semen contaminated with, infectious bovine rhinotracheitis virus.", "content": "Ten cows and heifers (Group B) were inoculated into the uterus at oestrus with semen followed by IBR virus for the first insemination and semen alone if a second insemination was necessary. All animals developed infectious pustular vulvo-vaginitis (IPV), and 2 cows conceived to the first and 2 to the second insemination (pregnancy rate of 40 percent requiring 4.5 services per conception). This group was compared with 10 control animals (Group A) which were treated similarly but received tissue culture fluid instead of virus at the first insemination. Group A had a pregnancy rate of 90 percent requiring 1.7 services per conception. Natural mating of 4 bulls with preputial infections due to infectious bovine rhinotracheitis (IBR) virus with 9 susceptible cows and heifers (group D), resulted in the production of lesions of IPV. The IPV infection did not affect their fertility (pregnancy rate of 89 percent requiring 1.4 services per conception) when it was compared to a similar group of females (group C) mated to the same bulls prior to infection with IBR virus (pregnancy rate of 100 percent requiring 1.2 services per conception). The 6 animals in Group B that were not pregnant and returned to oestrus 3 times were found on slaughter to have endometritis, salpingitis and vaginitis. A high incidence, 5 out of 18 (28 percent), of shortened oestrous cycles (less than 18 days) was a feature of the breeding pattern of this group. The undesirable consequences of distributing semen contaminated with IBR virus from artificial insemination centres are apparent.", "contents": "The effect of natural and artificial breeding using bulls infected with, or semen contaminated with, infectious bovine rhinotracheitis virus. Ten cows and heifers (Group B) were inoculated into the uterus at oestrus with semen followed by IBR virus for the first insemination and semen alone if a second insemination was necessary. All animals developed infectious pustular vulvo-vaginitis (IPV), and 2 cows conceived to the first and 2 to the second insemination (pregnancy rate of 40 percent requiring 4.5 services per conception). This group was compared with 10 control animals (Group A) which were treated similarly but received tissue culture fluid instead of virus at the first insemination. Group A had a pregnancy rate of 90 percent requiring 1.7 services per conception. Natural mating of 4 bulls with preputial infections due to infectious bovine rhinotracheitis (IBR) virus with 9 susceptible cows and heifers (group D), resulted in the production of lesions of IPV. The IPV infection did not affect their fertility (pregnancy rate of 89 percent requiring 1.4 services per conception) when it was compared to a similar group of females (group C) mated to the same bulls prior to infection with IBR virus (pregnancy rate of 100 percent requiring 1.2 services per conception). The 6 animals in Group B that were not pregnant and returned to oestrus 3 times were found on slaughter to have endometritis, salpingitis and vaginitis. A high incidence, 5 out of 18 (28 percent), of shortened oestrous cycles (less than 18 days) was a feature of the breeding pattern of this group. The undesirable consequences of distributing semen contaminated with IBR virus from artificial insemination centres are apparent."} {"id": "PMID:172056", "title": "Studies on the effects of infectious bovine rhinotracheitis virus on reproduction in heifers.", "content": "Natural venereal infection of heifers with IBR virus resulted in vulvovaginal lesions in 9 of 12 heifers at 3 weeks after introducttion to bulls, and virus was isolated from 5 of the 9 affected animals. The infection was not associated with any effect on conception. Experimental nasal and conjunctival infection of 18 heifers pregnant for 3, 5 or 7 months with a genital strain of IBR virus caused mild rhinitis or conjunctivitis in all inoculated animals and virus was recovered from 14 animals at 8 days after inoculation. No effects on pregnancy were recorded.", "contents": "Studies on the effects of infectious bovine rhinotracheitis virus on reproduction in heifers. Natural venereal infection of heifers with IBR virus resulted in vulvovaginal lesions in 9 of 12 heifers at 3 weeks after introducttion to bulls, and virus was isolated from 5 of the 9 affected animals. The infection was not associated with any effect on conception. Experimental nasal and conjunctival infection of 18 heifers pregnant for 3, 5 or 7 months with a genital strain of IBR virus caused mild rhinitis or conjunctivitis in all inoculated animals and virus was recovered from 14 animals at 8 days after inoculation. No effects on pregnancy were recorded."} {"id": "PMID:172058", "title": "Maintenance of DNA and repair of Apurinic sites.", "content": "Escherichia coli cells contain an enzyme which hydrolyzes a phosphodiester bond near each apurinic site in double-stranded DNA. This endonuclease is specific for apurinic sites; it has no effect on normal DNA, and its action on alkylated DNA is restricted to apurinic sites. In vitro incubation with the endonuclease for apurinic sites, DNA polymerase I, and ligase permits repair of DNA containing apurinic sites. The endonuclease for apurinic sites might thus play a role in cell survival after a treatment with alkylating agents; as DNA spontaneously loses purines, the enzyme might also play a role in the maintance of a normal DNA in every cell. Indeed, an endonuclease for apurinic sites has been found not only in bacteria but also in animal and plant cells; it is very active in thermophilic bacteria.", "contents": "Maintenance of DNA and repair of Apurinic sites. Escherichia coli cells contain an enzyme which hydrolyzes a phosphodiester bond near each apurinic site in double-stranded DNA. This endonuclease is specific for apurinic sites; it has no effect on normal DNA, and its action on alkylated DNA is restricted to apurinic sites. In vitro incubation with the endonuclease for apurinic sites, DNA polymerase I, and ligase permits repair of DNA containing apurinic sites. The endonuclease for apurinic sites might thus play a role in cell survival after a treatment with alkylating agents; as DNA spontaneously loses purines, the enzyme might also play a role in the maintance of a normal DNA in every cell. Indeed, an endonuclease for apurinic sites has been found not only in bacteria but also in animal and plant cells; it is very active in thermophilic bacteria."} {"id": "PMID:172059", "title": "Influence of repair on the specificity of ultraviolet-induced reversion of an ochre alleles of the structural gene for iso-1-cytochrome c.", "content": "The specific action of UV on the reversion of the ochre allele cycl-9, in which 21 out of 23 revertants have been shown to arise from A-T-to-G.C transitions at position one in the UAA codon, was found to depend on the function of the RAD6 gene, since cycl-9 reversion occurred by a variety of single-base-pair substitutions in a strain carrying the rad6-1 allele.", "contents": "Influence of repair on the specificity of ultraviolet-induced reversion of an ochre alleles of the structural gene for iso-1-cytochrome c. The specific action of UV on the reversion of the ochre allele cycl-9, in which 21 out of 23 revertants have been shown to arise from A-T-to-G.C transitions at position one in the UAA codon, was found to depend on the function of the RAD6 gene, since cycl-9 reversion occurred by a variety of single-base-pair substitutions in a strain carrying the rad6-1 allele."} {"id": "PMID:172062", "title": "Repair of DNA strand breaks in progeric fibroblasts and aging human diploid cells.", "content": "The rate of rejoining of DNA strand breaks induced by 10 krad of gamma-irradiation has been studied in normal human diploid skin fibroblasts and in skin fibroblasts from six patients with symptoms of progeria. Although slightly more rapid in very early passage, the repair rate in normal cells was similar throughout most of their life span in vitro. The appearance of cells with reduced repair capacity was evident as the cultures became senescent. The progeric fibroblasts varied greatly in their response to irradiation. The rate of repair was greatly reduced in two strains, whereas in two others extensive DNA degradation was consistently observed in unirradiated cells. Degradation was apparently related to the radiation received from the incorporated radiolabel. Normal repair was seen in progeric fibroblasts transformed by SV40 virus.", "contents": "Repair of DNA strand breaks in progeric fibroblasts and aging human diploid cells. The rate of rejoining of DNA strand breaks induced by 10 krad of gamma-irradiation has been studied in normal human diploid skin fibroblasts and in skin fibroblasts from six patients with symptoms of progeria. Although slightly more rapid in very early passage, the repair rate in normal cells was similar throughout most of their life span in vitro. The appearance of cells with reduced repair capacity was evident as the cultures became senescent. The progeric fibroblasts varied greatly in their response to irradiation. The rate of repair was greatly reduced in two strains, whereas in two others extensive DNA degradation was consistently observed in unirradiated cells. Degradation was apparently related to the radiation received from the incorporated radiolabel. Normal repair was seen in progeric fibroblasts transformed by SV40 virus."} {"id": "PMID:172065", "title": "Radio-enzymic assay of oxo steroids by their reduction with the tritiated form of reduced nicotinamide--adenine dinucleotide.", "content": "A method of analysis is proposed based on the enzyme-catalysed transfer of tritium from [3H]NADH to suitable substrates. Its practicability is demonstrated on the examples of oestrone and progesterone with the respective use of the 3 beta, 17 beta- and 3 alpha, 20 beta-hydroxysteroid oxidoreductase. Specificity is tested by application to the analysis of the plasma of pregnant women and measurement of the 3H/14C ratios on purification of the enzymic reduction products.", "contents": "Radio-enzymic assay of oxo steroids by their reduction with the tritiated form of reduced nicotinamide--adenine dinucleotide. A method of analysis is proposed based on the enzyme-catalysed transfer of tritium from [3H]NADH to suitable substrates. Its practicability is demonstrated on the examples of oestrone and progesterone with the respective use of the 3 beta, 17 beta- and 3 alpha, 20 beta-hydroxysteroid oxidoreductase. Specificity is tested by application to the analysis of the plasma of pregnant women and measurement of the 3H/14C ratios on purification of the enzymic reduction products."} {"id": "PMID:172066", "title": "Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines.", "content": "Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.", "contents": "Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines. Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation."} {"id": "PMID:172063", "title": "The contribution of atrial stretch receptors to salt and water homeostasis in the human.", "content": "Studies carried out in both the human and experimental animals provide reasonably strong evidence that receptors contained within the atria are involved in the control of body water. When atrial pressure is increased (and the atria distended) atrial receptor discharge is increased leading to an increase in urine flow and, depending upon the experimental condition, a less consistent increase in sodium excretion. At least two mechanisms appear to contribute to the renal response; inhibition of the secretion of antidiuretic hormone and inhibition of renal nerve discharge. None of the factors presently known to alter sodium excretion have been shown to account completely for the increase in sodium excretion. The failure of patients with chronically distended atria to experience a chronic diuresis appears to be partly the result of a resetting of atrial receptor sensitivity. Recent evidence suggests that the sensitivity of atrial volume receptors has a species variation.", "contents": "The contribution of atrial stretch receptors to salt and water homeostasis in the human. Studies carried out in both the human and experimental animals provide reasonably strong evidence that receptors contained within the atria are involved in the control of body water. When atrial pressure is increased (and the atria distended) atrial receptor discharge is increased leading to an increase in urine flow and, depending upon the experimental condition, a less consistent increase in sodium excretion. At least two mechanisms appear to contribute to the renal response; inhibition of the secretion of antidiuretic hormone and inhibition of renal nerve discharge. None of the factors presently known to alter sodium excretion have been shown to account completely for the increase in sodium excretion. The failure of patients with chronically distended atria to experience a chronic diuresis appears to be partly the result of a resetting of atrial receptor sensitivity. Recent evidence suggests that the sensitivity of atrial volume receptors has a species variation."} {"id": "PMID:172067", "title": "Molecular mechanisms in alkylation mutagenesis. Induced reversion of bacteriophage T4rII AP72 by ethyl methanesulphonate in relation to extent and mode of ethylation of purines in bacteriophage deoxyribonucleic acid.", "content": "Survival and reversion to T4r+ of bacteriophage T4rII AP72 after treatment with ethyl methanesulphonate at 37 degrees or 45 degrees C were studied in relation to the extent and mode of alkylation of purines in DNA of ethylated bacteriophage. A single-burst technique was used for reversion assay. Survival was lower at 45 degrees C than at 37 degrees C at a given extent of ethylation of bacteriophage DNA, confirming that events subsequent to ethylation, probably depurinations, are the main cause of decreased survival. Reversion was positively correlated (approximately linearly except at low extents at 37 degrees C) with ethylation of bacteriophage DNA, showing that ethylation itself causes mutation. Following the concept that reversion results from G-C leads to A-T transition at a single site (Krieg, 1963a,b) and the suggestion that O6-alkylation of guanine generates the miscoding base (Loveless, 1969), it was calculated that about one-third of induced O6-ethylguanines at this site would miscode to induce mutation.", "contents": "Molecular mechanisms in alkylation mutagenesis. Induced reversion of bacteriophage T4rII AP72 by ethyl methanesulphonate in relation to extent and mode of ethylation of purines in bacteriophage deoxyribonucleic acid. Survival and reversion to T4r+ of bacteriophage T4rII AP72 after treatment with ethyl methanesulphonate at 37 degrees or 45 degrees C were studied in relation to the extent and mode of alkylation of purines in DNA of ethylated bacteriophage. A single-burst technique was used for reversion assay. Survival was lower at 45 degrees C than at 37 degrees C at a given extent of ethylation of bacteriophage DNA, confirming that events subsequent to ethylation, probably depurinations, are the main cause of decreased survival. Reversion was positively correlated (approximately linearly except at low extents at 37 degrees C) with ethylation of bacteriophage DNA, showing that ethylation itself causes mutation. Following the concept that reversion results from G-C leads to A-T transition at a single site (Krieg, 1963a,b) and the suggestion that O6-alkylation of guanine generates the miscoding base (Loveless, 1969), it was calculated that about one-third of induced O6-ethylguanines at this site would miscode to induce mutation."} {"id": "PMID:172068", "title": "A method for investigating the effect of temperature on the 695 nm band of insoluble cytochrome c.", "content": "A method is described for computer analysis of simple spectrophotometric changes in particulate systems, and this has been applied to the bleaching of the 695 nm band of insoluble ferricytochrome c by temperature. The results show that insolubilization has no effect on the standard enthalpy change but lowers the value for the standard entropy change. This effect appears to be independent of the concentration of the gel matrix to which the cytochrome c is bound, but dependent on the ionic strength of the surrounding solution.", "contents": "A method for investigating the effect of temperature on the 695 nm band of insoluble cytochrome c. A method is described for computer analysis of simple spectrophotometric changes in particulate systems, and this has been applied to the bleaching of the 695 nm band of insoluble ferricytochrome c by temperature. The results show that insolubilization has no effect on the standard enthalpy change but lowers the value for the standard entropy change. This effect appears to be independent of the concentration of the gel matrix to which the cytochrome c is bound, but dependent on the ionic strength of the surrounding solution."} {"id": "PMID:172069", "title": "A double-beam rapid-scanning stopped-flow spectrophotometer.", "content": "A double-beam rapid-wavelength-scanning stopped-flow spectrophotometer system based on the Norcon model 501 spectrometer was construced, which enables u.v.-or visible absorbance spectra to be recorded at the rate of 800/s after the rapid mixing (within 3ms) of two reactant solutions. Each spectrum spans about 200nm in 1ms. It is possible to record difference spectra during reactions with half-lives less than 10ms involving absorbance changes of less than 0.1 absorbance unit. Analogue circuitry is used to produce spectra of absorbance against wavelength. Up to 32 such spectra can be recorded at pre-selected times during a reaction and stored in an 8Kx8-bit-word hard-wired data-capture system to be subsequently displaned individually or simultaneously. Time-courses at different wavelengths can also be displayed. By averaging up to 216 spectra it is possible to record spectra under conditions of low signal-to-noise ratios...", "contents": "A double-beam rapid-scanning stopped-flow spectrophotometer. A double-beam rapid-wavelength-scanning stopped-flow spectrophotometer system based on the Norcon model 501 spectrometer was construced, which enables u.v.-or visible absorbance spectra to be recorded at the rate of 800/s after the rapid mixing (within 3ms) of two reactant solutions. Each spectrum spans about 200nm in 1ms. It is possible to record difference spectra during reactions with half-lives less than 10ms involving absorbance changes of less than 0.1 absorbance unit. Analogue circuitry is used to produce spectra of absorbance against wavelength. Up to 32 such spectra can be recorded at pre-selected times during a reaction and stored in an 8Kx8-bit-word hard-wired data-capture system to be subsequently displaned individually or simultaneously. Time-courses at different wavelengths can also be displayed. By averaging up to 216 spectra it is possible to record spectra under conditions of low signal-to-noise ratios..."} {"id": "PMID:172070", "title": "A sensitive radiochemical assay for angiotensin-converting enzyme (kinase II).", "content": "[[125I]Tyr8]Bradykinin is degraded by angiotensin-converting enzyme to [125I]Tyr-Arg. The reaction product can be separated completely and recovered nearly quantitatively from unchanged substrate by cation-exchange chromatography. Thus it is possible to use [[125I]Tyr8]bradykinin at high specific radioactivity (about 400Ci/mmol) to measure the small quantities of angiotensin-converting enzyme encountered in small-scale cultures of pulmonary endothelial cells.", "contents": "A sensitive radiochemical assay for angiotensin-converting enzyme (kinase II). [[125I]Tyr8]Bradykinin is degraded by angiotensin-converting enzyme to [125I]Tyr-Arg. The reaction product can be separated completely and recovered nearly quantitatively from unchanged substrate by cation-exchange chromatography. Thus it is possible to use [[125I]Tyr8]bradykinin at high specific radioactivity (about 400Ci/mmol) to measure the small quantities of angiotensin-converting enzyme encountered in small-scale cultures of pulmonary endothelial cells."} {"id": "PMID:172071", "title": "The isolation of collagen-associated proteoglycan from bovine nasal cartilage and its preferential interaction with alpha2 chains of type I collagen.", "content": "A collagen complex from bovine nasal cartilage was prepared by extraction of the tissue with 3M-MgCl2 solutions, by using two different procedures. When it was compared with calf skin acid-soluble tropocollagen by polyacrylamide-gel electrophoresis, the 3M-MgCl2-soluble cartilage collagen in the complex appeared to be predominantly type I in nature, consisting of both alpha1 and alpha2 chains. The soluble cartilage collagens were digested with purified bacterial collagenase, and the soluble digests were fractionated on Sepharose 4B. Hydroxyproline-free proteoglycan was isolated in the excluded volume of the column eluate, and this was found to be an aggregate which could be dissociated to link proteins and proteoglycan subunit by equilibrium-density-gradient centrifugation in a CsCl-4M-guanidinium chloride gradient. Interaction with calf skin-soluble tropocollagen was studied by CM-cellulose chromatography. The link-protein system did not interact, but proteoglycan from the bottom of the gradient did interact. In addition, when proteoglycan subunit was allowed to interact with collagen, there was a preferential binding to the alpha2 and beta12 components, and this effect was also observed with the proteoglycan material obtained from the collagenase digests of 3M-MgCl2-soluble cartilage collagen complexes. However, specificity for alpha2 and beta12 chains was not exhibited by chondroitin sulphate glycosaminoglycan, and it is therefore concluded that preference for alpha2 and beta12 chains is a function of the intact proteoglycan structure.", "contents": "The isolation of collagen-associated proteoglycan from bovine nasal cartilage and its preferential interaction with alpha2 chains of type I collagen. A collagen complex from bovine nasal cartilage was prepared by extraction of the tissue with 3M-MgCl2 solutions, by using two different procedures. When it was compared with calf skin acid-soluble tropocollagen by polyacrylamide-gel electrophoresis, the 3M-MgCl2-soluble cartilage collagen in the complex appeared to be predominantly type I in nature, consisting of both alpha1 and alpha2 chains. The soluble cartilage collagens were digested with purified bacterial collagenase, and the soluble digests were fractionated on Sepharose 4B. Hydroxyproline-free proteoglycan was isolated in the excluded volume of the column eluate, and this was found to be an aggregate which could be dissociated to link proteins and proteoglycan subunit by equilibrium-density-gradient centrifugation in a CsCl-4M-guanidinium chloride gradient. Interaction with calf skin-soluble tropocollagen was studied by CM-cellulose chromatography. The link-protein system did not interact, but proteoglycan from the bottom of the gradient did interact. In addition, when proteoglycan subunit was allowed to interact with collagen, there was a preferential binding to the alpha2 and beta12 components, and this effect was also observed with the proteoglycan material obtained from the collagenase digests of 3M-MgCl2-soluble cartilage collagen complexes. However, specificity for alpha2 and beta12 chains was not exhibited by chondroitin sulphate glycosaminoglycan, and it is therefore concluded that preference for alpha2 and beta12 chains is a function of the intact proteoglycan structure."} {"id": "PMID:172096", "title": "Serum lipids in young female survivors of myocardial infarction.", "content": "Fasting serum lipids and lipoprotein patterns were studied in 44 female survivors of acute myocardial infarction under the age of 45 years, and in 84 matched control subjects. Type II hyperlipoproteinaemia was present in 41 per cent of the myocardial infarction patients and in none of the controls. There was, however, no difference in the prevalence of the type IV abnormality, which was present in 7 per cent of the myocardial infarction patients and 8 per cent of the control subjects. Mean cholesterol and triglyceride levels were both significantly higher in the women who had survived myocardial infarction than in the controls; the difference in triglyceride was attributable to the type IIb abnormality which occurred in 11 per cent of these patients. It is suggested that ovarian hormones may protect premenopausal women from type IV hyperlipoproteinaemia and its possible atherogenic sequelae.", "contents": "Serum lipids in young female survivors of myocardial infarction. Fasting serum lipids and lipoprotein patterns were studied in 44 female survivors of acute myocardial infarction under the age of 45 years, and in 84 matched control subjects. Type II hyperlipoproteinaemia was present in 41 per cent of the myocardial infarction patients and in none of the controls. There was, however, no difference in the prevalence of the type IV abnormality, which was present in 7 per cent of the myocardial infarction patients and 8 per cent of the control subjects. Mean cholesterol and triglyceride levels were both significantly higher in the women who had survived myocardial infarction than in the controls; the difference in triglyceride was attributable to the type IIb abnormality which occurred in 11 per cent of these patients. It is suggested that ovarian hormones may protect premenopausal women from type IV hyperlipoproteinaemia and its possible atherogenic sequelae."} {"id": "PMID:172092", "title": "Wrist arthropathy in calcium pyrophosphate dihydrate deposition disease.", "content": "Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. In the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. Two investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chondrocalcinosis and the diagnosis is strongly suggested by a characteristic radiographic picture.", "contents": "Wrist arthropathy in calcium pyrophosphate dihydrate deposition disease. Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. In the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. Two investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chondrocalcinosis and the diagnosis is strongly suggested by a characteristic radiographic picture."} {"id": "PMID:172091", "title": "Connective tissue activation. IX. Modification by pharmacologic agents.", "content": "Alpha- and beta-adrenergic blocking agents and imipramine inhibit the increased hyaluronate synthesis that may be induced in human synovial cultures by connective tissue activating peptide (CTAP). Considerations of drug concentration requirements, actions of analogues, and time studies all indicate that the adrenergic blockers do not act in this circumstance as conventional blockers of alpha or beta receptor sites. It is suggested that the membrane-stabilizing properties of these agents may be the important determinant for their limited \"antiactivation\" effect. Ethacrynic acid, a potent and more complete inhibitor of connective tissue activation, appears to act via a different mechanism.", "contents": "Connective tissue activation. IX. Modification by pharmacologic agents. Alpha- and beta-adrenergic blocking agents and imipramine inhibit the increased hyaluronate synthesis that may be induced in human synovial cultures by connective tissue activating peptide (CTAP). Considerations of drug concentration requirements, actions of analogues, and time studies all indicate that the adrenergic blockers do not act in this circumstance as conventional blockers of alpha or beta receptor sites. It is suggested that the membrane-stabilizing properties of these agents may be the important determinant for their limited \"antiactivation\" effect. Ethacrynic acid, a potent and more complete inhibitor of connective tissue activation, appears to act via a different mechanism."} {"id": "PMID:172098", "title": "Corticotrophin after corticosteroids in children with asthma and growth retardation.", "content": "A study of the growth patterns of 19 children with chronic asthma, whose growth had become retarded while they were receiving regular treatment with prednisolone, showed that this trend was reversed after the substitution of corticotrophin.", "contents": "Corticotrophin after corticosteroids in children with asthma and growth retardation. A study of the growth patterns of 19 children with chronic asthma, whose growth had become retarded while they were receiving regular treatment with prednisolone, showed that this trend was reversed after the substitution of corticotrophin."} {"id": "PMID:172094", "title": "ACTH content of pituitary glands of arteriosclerotic breeder vs. non-arteriosclerotic virgin rats.", "content": "Acid extracts were made of the pituitary glands of non-arteriosclerotic male and female virgin rats and arteriosclerotic, male and female breeder rats. The ACTH content of these pituitary glands was determined by measuring the amount of corticosterone produced by the adrenal glands of healthy but hypophysectomized rats when challenged by the various ACTH acid extracts. The pituitary glands of the arteriosclerotic animals were significantly heavier than non-arteriosclerotic rats and contained decreased amounts of ACTH commensurate with the severity of the pituitary donor's arteriosclerosis. Similarly, arteriosclerotic donors had heavier adrenal glands but contained considerably less corticosterone than non-arteriosclerotic virgin rats. Male breeder rats developed microscopic aortic lesions involving intimal mesenchymal cell and ground substance alterations whereas the female breeder lesions progressed from intimal ground substance and connective tissue changes to medial elastolytic degeneration and eventual medial cartilaginous and osseous metaplasia. Histopathologic examination of the pituitary and adrenal glands demonstrated hyperplasia of basophil and other cytologic elements of the pituitary gland including colloid-filled cysts and lipid depletion of the zona glomerulosa as well as hemorrhage and thrombosis of the adrenal cortex of the arteriosclerotic breeder rats. The hypothesis is made that repeated breeding leads to abnormal hypothalamic regulation of pituitary gland synthesis and release of ACTH, which, in turn, contributes to abnormal adrenal glandular function conditioning the aortic wall toward abnormal changes in mesenchymal cell activity and metabolism of connective tissue ground substance.", "contents": "ACTH content of pituitary glands of arteriosclerotic breeder vs. non-arteriosclerotic virgin rats. Acid extracts were made of the pituitary glands of non-arteriosclerotic male and female virgin rats and arteriosclerotic, male and female breeder rats. The ACTH content of these pituitary glands was determined by measuring the amount of corticosterone produced by the adrenal glands of healthy but hypophysectomized rats when challenged by the various ACTH acid extracts. The pituitary glands of the arteriosclerotic animals were significantly heavier than non-arteriosclerotic rats and contained decreased amounts of ACTH commensurate with the severity of the pituitary donor's arteriosclerosis. Similarly, arteriosclerotic donors had heavier adrenal glands but contained considerably less corticosterone than non-arteriosclerotic virgin rats. Male breeder rats developed microscopic aortic lesions involving intimal mesenchymal cell and ground substance alterations whereas the female breeder lesions progressed from intimal ground substance and connective tissue changes to medial elastolytic degeneration and eventual medial cartilaginous and osseous metaplasia. Histopathologic examination of the pituitary and adrenal glands demonstrated hyperplasia of basophil and other cytologic elements of the pituitary gland including colloid-filled cysts and lipid depletion of the zona glomerulosa as well as hemorrhage and thrombosis of the adrenal cortex of the arteriosclerotic breeder rats. The hypothesis is made that repeated breeding leads to abnormal hypothalamic regulation of pituitary gland synthesis and release of ACTH, which, in turn, contributes to abnormal adrenal glandular function conditioning the aortic wall toward abnormal changes in mesenchymal cell activity and metabolism of connective tissue ground substance."} {"id": "PMID:172099", "title": "The effects of iron deficiency on rat liver enzymes.", "content": "The effect of iron deficiency on a number or iron containing enzymes in rat liver has been examined. In addition, 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase have been assayed. Of the mitochondrial electron transport reactions only succinate-cytochrome C reductase activity was decreased in iron deficient animals. Microsomal reductase enzymes associated with the NADPH-oxidase system were also markedly decreased although cytochrome P450 concentrations were unaffected. Both 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were reduced in young iron deficient rats but the former had returned to control levels at the age of 14 weeks.", "contents": "The effects of iron deficiency on rat liver enzymes. The effect of iron deficiency on a number or iron containing enzymes in rat liver has been examined. In addition, 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase have been assayed. Of the mitochondrial electron transport reactions only succinate-cytochrome C reductase activity was decreased in iron deficient animals. Microsomal reductase enzymes associated with the NADPH-oxidase system were also markedly decreased although cytochrome P450 concentrations were unaffected. Both 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were reduced in young iron deficient rats but the former had returned to control levels at the age of 14 weeks."} {"id": "PMID:172100", "title": "In vivo microscopic observations of the pathogenesis of acute mouse viral hepatitis.", "content": "In vivo microscopy of the liver was undertaken to determine the extent of involvement of the hepatic microvascular system in mice infected with viral hepatitis (MHV-3). It was found that the major effects of the disease were produced in localized areas where parenchyma, sinusoids and blood were obliterated. However, immediately peripheral to these lesions blood flow and vessels were unaffected other than by localized hypertrophy of K\u00fcpffer cells. While each lesion produced a sinusoidal block to blood flow, portal hypertension did not occur even in the presence of extensive focal and confluent necrosis.", "contents": "In vivo microscopic observations of the pathogenesis of acute mouse viral hepatitis. In vivo microscopy of the liver was undertaken to determine the extent of involvement of the hepatic microvascular system in mice infected with viral hepatitis (MHV-3). It was found that the major effects of the disease were produced in localized areas where parenchyma, sinusoids and blood were obliterated. However, immediately peripheral to these lesions blood flow and vessels were unaffected other than by localized hypertrophy of K\u00fcpffer cells. While each lesion produced a sinusoidal block to blood flow, portal hypertension did not occur even in the presence of extensive focal and confluent necrosis."} {"id": "PMID:172095", "title": "Effects of dextrothyroxine on hyperlipidemia and experimental atherosclerosis in beagle dogs.", "content": "Beagle dogs, 24 +/- 6 months old, fed a thiouracil-free semi-synthetic diet containing hydrogenated coconut oil and cholesterol (SS diet) for 12 months, developed marked hyperlipidemia and severe atherosclerosis. SS diet produced a marked elevation of serum cholesterol, triglyceride, phospholipid, and beta-lipoprotein and severe atherosclerosis in large and small arteries. Intimal fatty lesions were always present in the abdominal aorta and many of its branches. Large and small coronary arteries showed similar lesions. The degree of atherosclerosis was directly related to circulating lipid levels. Dextrothyroxine, at dose levels of 0.1 (equivalent to normal human dose) and 0.5 mg/kg body weight, produced a significant dose related lowering of serum lipids and was associated with a markedly decreased severity of aortic and coronary artery lesions. Untreated control dogs that were maintained on purina dog meal developed neither hyperlipidemia nor atherosclerosis.", "contents": "Effects of dextrothyroxine on hyperlipidemia and experimental atherosclerosis in beagle dogs. Beagle dogs, 24 +/- 6 months old, fed a thiouracil-free semi-synthetic diet containing hydrogenated coconut oil and cholesterol (SS diet) for 12 months, developed marked hyperlipidemia and severe atherosclerosis. SS diet produced a marked elevation of serum cholesterol, triglyceride, phospholipid, and beta-lipoprotein and severe atherosclerosis in large and small arteries. Intimal fatty lesions were always present in the abdominal aorta and many of its branches. Large and small coronary arteries showed similar lesions. The degree of atherosclerosis was directly related to circulating lipid levels. Dextrothyroxine, at dose levels of 0.1 (equivalent to normal human dose) and 0.5 mg/kg body weight, produced a significant dose related lowering of serum lipids and was associated with a markedly decreased severity of aortic and coronary artery lesions. Untreated control dogs that were maintained on purina dog meal developed neither hyperlipidemia nor atherosclerosis."} {"id": "PMID:172103", "title": "Is the cyclic AMP in psoriatic epidermis low?", "content": "A deficiency of epidermal cyclic adenosine 3', 5'-monophosphate (cyclic AMP) has been implicated as the cause of the incomplete differentiation, increased mitosis and increased glycogen concentration which characterize the psoriatic lesion. This communication contains our data on the epidermal concentration of cyclic AMP in the lesional and 'normal' (non-involved) skin of patients with psoriasis. In these studies we have introduced the following improvement in methodology: (1) Local ischaemia in the biopsy specimens was prevented by not giving any injections prior to removal of the tissues and by freezing the tissues prior to removal. (2) The epidermis was microdissected from the dermis prior to cyclic AMP assay as as to give as pure an epidermal specimen as possible. Epidermal cyclic AMP was found to be 20-25% higher in the skin lesion than in the uninvolved skin when compared on a dry weight or protein basis but essentially when compared on the basis of DNA content. Our conclusion is that the cyclic AMP level in the psoriatic lesion is not lower than that in the 'normal' skin and thus these characteristics in psoriatic lesions cannot be related simply to a cyclic AMP deficiency.", "contents": "Is the cyclic AMP in psoriatic epidermis low? A deficiency of epidermal cyclic adenosine 3', 5'-monophosphate (cyclic AMP) has been implicated as the cause of the incomplete differentiation, increased mitosis and increased glycogen concentration which characterize the psoriatic lesion. This communication contains our data on the epidermal concentration of cyclic AMP in the lesional and 'normal' (non-involved) skin of patients with psoriasis. In these studies we have introduced the following improvement in methodology: (1) Local ischaemia in the biopsy specimens was prevented by not giving any injections prior to removal of the tissues and by freezing the tissues prior to removal. (2) The epidermis was microdissected from the dermis prior to cyclic AMP assay as as to give as pure an epidermal specimen as possible. Epidermal cyclic AMP was found to be 20-25% higher in the skin lesion than in the uninvolved skin when compared on a dry weight or protein basis but essentially when compared on the basis of DNA content. Our conclusion is that the cyclic AMP level in the psoriatic lesion is not lower than that in the 'normal' skin and thus these characteristics in psoriatic lesions cannot be related simply to a cyclic AMP deficiency."} {"id": "PMID:172104", "title": "A method of liberating living cells from the dermal infiltrate.", "content": "A new technique is described whereby viable infiltrating cells can be freed from skin biopsy specimens. The specimens are incubated with collagenase and then mechanically disaggregated. The liberated cells are still suitable for immunological and morphological study. Using this method, the nature of the dermal infiltrate in patients with skin reticuloses was compared with that in lichen planus. A predominance of T cells was found in mycosis fungoides, the Sezary syndrome, and lichen planus, and of B cells in non-Hodgkin lymphomas.", "contents": "A method of liberating living cells from the dermal infiltrate. A new technique is described whereby viable infiltrating cells can be freed from skin biopsy specimens. The specimens are incubated with collagenase and then mechanically disaggregated. The liberated cells are still suitable for immunological and morphological study. Using this method, the nature of the dermal infiltrate in patients with skin reticuloses was compared with that in lichen planus. A predominance of T cells was found in mycosis fungoides, the Sezary syndrome, and lichen planus, and of B cells in non-Hodgkin lymphomas."} {"id": "PMID:172105", "title": "Further studies of scratching during sleep.", "content": "Fifteen patients with a variety of itching skin diseases (atopic eczema, dermatitis herpetiformis, lichen planus, urticaria and psoriasis) have been studied in the sleep laboratory. Recordings were made of all-night electroencephalogram, electro-oculogram, submental electromyogram, and muscle potentials from both forearms. Bouts of scratching during orthodox (NREM) sleep occurred more frequently in stages 1 and 2 than in stages 3 and 4. The frequency in paradoxial (REM) sleep was close to that in stage 2 sleep. This pattern was similar for all the diseases studied and seems to be related to the physiology of the sleep stages rather than to the skin diseases themselves. The mean duration of the bouts of scratching was not related to the sleep stage in which they started.", "contents": "Further studies of scratching during sleep. Fifteen patients with a variety of itching skin diseases (atopic eczema, dermatitis herpetiformis, lichen planus, urticaria and psoriasis) have been studied in the sleep laboratory. Recordings were made of all-night electroencephalogram, electro-oculogram, submental electromyogram, and muscle potentials from both forearms. Bouts of scratching during orthodox (NREM) sleep occurred more frequently in stages 1 and 2 than in stages 3 and 4. The frequency in paradoxial (REM) sleep was close to that in stage 2 sleep. This pattern was similar for all the diseases studied and seems to be related to the physiology of the sleep stages rather than to the skin diseases themselves. The mean duration of the bouts of scratching was not related to the sleep stage in which they started."} {"id": "PMID:172106", "title": "Unusual cutaneous associations of a malignant carcinoid tumour of the bronchus--erythema annulare centrifugum and white banding of the toe nails.", "content": "The case history of a patient who presented with erythema annulare centrifugum and white banding of the toe nails is recorded. On investigation for an underlying malignancy the patient was found to have an opacity in the lower lobe of the right lung. Subsequently lobectomy was performed and histology of the operative specimen revealed a malignant carcinoid tumour of the bronchus.", "contents": "Unusual cutaneous associations of a malignant carcinoid tumour of the bronchus--erythema annulare centrifugum and white banding of the toe nails. The case history of a patient who presented with erythema annulare centrifugum and white banding of the toe nails is recorded. On investigation for an underlying malignancy the patient was found to have an opacity in the lower lobe of the right lung. Subsequently lobectomy was performed and histology of the operative specimen revealed a malignant carcinoid tumour of the bronchus."} {"id": "PMID:172107", "title": "Absorption and biotransformation of topically applied 8-(methylthio) cyclic AMP. Studies in dogs and humans.", "content": "8-(Methylthiocyclic AMP-35S was applied topically to the intact or abraded skin of dogs at a dose of about 2-5 mg/kg. In this species, an average of 7% of the dose was absorbed through the intact and 62% through abraded skin. Half-lives for radioactivity in plasma averaged 3-6 h. After the topical application of the drug to the intact skin of dogs, the average concentration in plasma of glucose, but not of insulin, was increased by as much as 21%; after application to abraded skin, glucose and insulin were increased, on average, by as much as 84 and 221%, respectively. 8-(methylthio)adenosine and two unidentified compounds were present as metabolites in the urine of dogs; some unchanged 8-(methylthio)cyclic AMP-35S was also excreted. 8-(methylthio)cyclic AMP-35S was also applied topically (25 mg; 0-32 mg/kg) to the intact and stripped skin of normal human subjects under conditions similar to those used for dogs. Three subjects with intact skin did not absorb any of the drug, whereas three subjects with stripped skin absorbed 0-5, 8-3, and 23-3% of the dose. The half-life of radioactivity in the plasma of the subject with the greatest absorption was 0-5 h during the first 2 h, and 11 h for the next 10 h. During the first 2 h, this same subject excreted unchanged drug and 8-(methylthio)adenosine in his urine. No changes in glucose or insulin concentrations in plasma were observed in any of the subjects nor was there any apparent irritation of the skin.", "contents": "Absorption and biotransformation of topically applied 8-(methylthio) cyclic AMP. Studies in dogs and humans. 8-(Methylthiocyclic AMP-35S was applied topically to the intact or abraded skin of dogs at a dose of about 2-5 mg/kg. In this species, an average of 7% of the dose was absorbed through the intact and 62% through abraded skin. Half-lives for radioactivity in plasma averaged 3-6 h. After the topical application of the drug to the intact skin of dogs, the average concentration in plasma of glucose, but not of insulin, was increased by as much as 21%; after application to abraded skin, glucose and insulin were increased, on average, by as much as 84 and 221%, respectively. 8-(methylthio)adenosine and two unidentified compounds were present as metabolites in the urine of dogs; some unchanged 8-(methylthio)cyclic AMP-35S was also excreted. 8-(methylthio)cyclic AMP-35S was also applied topically (25 mg; 0-32 mg/kg) to the intact and stripped skin of normal human subjects under conditions similar to those used for dogs. Three subjects with intact skin did not absorb any of the drug, whereas three subjects with stripped skin absorbed 0-5, 8-3, and 23-3% of the dose. The half-life of radioactivity in the plasma of the subject with the greatest absorption was 0-5 h during the first 2 h, and 11 h for the next 10 h. During the first 2 h, this same subject excreted unchanged drug and 8-(methylthio)adenosine in his urine. No changes in glucose or insulin concentrations in plasma were observed in any of the subjects nor was there any apparent irritation of the skin."} {"id": "PMID:172108", "title": "Plane xanthomata associated with multiple myeloma and hyperlipoproteinaemia.", "content": "A case of plane xanthomatosis associated with multiple myeloma and hyperlipoproteinaemia in a 62-year-old woman is reported. The patient had IgG type lambda paraproteinaemia and type II A hyperlipoproteinaemia. The IgG paraprotein showed binding activity against high-density lipoprotein. It could not be demonstrated that these paraprotein-lipoprotein complexes were responsible for the hyperlipidaemia. Microchemical analysis of pathological skin demonstrated a high content of triglycerides, similar to that in eruptive xanthomata. No correlation was found between the lipid composition of the xanthomatous skin and the serum lipid composition. The results obtained with an in vitro culture method showed that the paraprotein present in the patient's serum was synthesized in the bone marrow but not in the normal or pathological skin.", "contents": "Plane xanthomata associated with multiple myeloma and hyperlipoproteinaemia. A case of plane xanthomatosis associated with multiple myeloma and hyperlipoproteinaemia in a 62-year-old woman is reported. The patient had IgG type lambda paraproteinaemia and type II A hyperlipoproteinaemia. The IgG paraprotein showed binding activity against high-density lipoprotein. It could not be demonstrated that these paraprotein-lipoprotein complexes were responsible for the hyperlipidaemia. Microchemical analysis of pathological skin demonstrated a high content of triglycerides, similar to that in eruptive xanthomata. No correlation was found between the lipid composition of the xanthomatous skin and the serum lipid composition. The results obtained with an in vitro culture method showed that the paraprotein present in the patient's serum was synthesized in the bone marrow but not in the normal or pathological skin."} {"id": "PMID:172109", "title": "Granulocyte function in chronic granulocytic leukaemia. I. Bactericidal and metabolic capabilities during phagocytosis in isolated granulocytes.", "content": "The ingestion, bactericidal activity and metabolism of isolated mature neutrophil leucocytes during phagocytosis was studied in 17 patients with chronic granulocytic leukaemia (CGL) with the simultaneous use of normal controls. Seven patients had received no treatment and the others had been treated previously with Busulphan. The phagocytic indices for killed yeast cells did not differ from those of the controls. A diminished bactericidal activity against E. coli was found in nine CGL cases. The bactericidal capacity closely correlated with the degree of leucocytosis since patients with a WBC count of 90 000/mul or higher with one exception showed decreased bactericidal activities while patients with WBC counts below 90 000/mul with two exceptions showed normal bactericidal activities. The [I-14C]-glucose oxidation during phagocytosis was increased in four patients and decreased in three patients. Some correlation was found between abnormally high or low [I-14C]glucose oxidation and diminished bactericidal activity. The intracellular iodination reaction during phagocytosis was decreased in 10 cases while the extracellular iodination was increased in six cases and decreased in one case. The data for granulocyte iodination did not correlate with WBC count, bactericidal capacity or [I-14C]glucose oxidation. The time course for the bactericidal activity and granulocyte iodination seemed to deviate from the controls indicating a slow initial ingestion and/or degranulation phase. The CGL granulocyte content of myeloperoxidase was normal or increased, the lysozyme content was decreased in half of the cases while the amount of antibacterial cationic proteins was increased, normal or low. The present findings indicate a variety of abnormalities in the mature CGL granulocyte, which are not closely interrelated.", "contents": "Granulocyte function in chronic granulocytic leukaemia. I. Bactericidal and metabolic capabilities during phagocytosis in isolated granulocytes. The ingestion, bactericidal activity and metabolism of isolated mature neutrophil leucocytes during phagocytosis was studied in 17 patients with chronic granulocytic leukaemia (CGL) with the simultaneous use of normal controls. Seven patients had received no treatment and the others had been treated previously with Busulphan. The phagocytic indices for killed yeast cells did not differ from those of the controls. A diminished bactericidal activity against E. coli was found in nine CGL cases. The bactericidal capacity closely correlated with the degree of leucocytosis since patients with a WBC count of 90 000/mul or higher with one exception showed decreased bactericidal activities while patients with WBC counts below 90 000/mul with two exceptions showed normal bactericidal activities. The [I-14C]-glucose oxidation during phagocytosis was increased in four patients and decreased in three patients. Some correlation was found between abnormally high or low [I-14C]glucose oxidation and diminished bactericidal activity. The intracellular iodination reaction during phagocytosis was decreased in 10 cases while the extracellular iodination was increased in six cases and decreased in one case. The data for granulocyte iodination did not correlate with WBC count, bactericidal capacity or [I-14C]glucose oxidation. The time course for the bactericidal activity and granulocyte iodination seemed to deviate from the controls indicating a slow initial ingestion and/or degranulation phase. The CGL granulocyte content of myeloperoxidase was normal or increased, the lysozyme content was decreased in half of the cases while the amount of antibacterial cationic proteins was increased, normal or low. The present findings indicate a variety of abnormalities in the mature CGL granulocyte, which are not closely interrelated."} {"id": "PMID:172111", "title": "Partial myeloperoxidase deficiency in a case of preleukaemia. I. Studies of fine structure and peroxidase synthesis of promyelocytes.", "content": "The ultrastructural localization of peroxidase activity has been studied in the circulating neutrophils and in a neutrophilic series of bone marrow cells from a patient with preleukaemia. Light microscopic examination showed 36% of the polymorphonuclear leucocytes to be totally devoid of myeloperoxidase, while 50% were normally stained and 14% were slightly positive for this enzyme. Electron microscopic studies revealed considerable heterogeneity in the promyelocyte population, since the number of peroxidase-deficient azurophil granules was seen to vary from 0 to 100% in these cells. Thus, several types of promyelocytes were identified. One cell type, which resembled that seen in normal subjects, contained myeloperoxidase within its azurophil granules and also within the cisternae of the rough endoplasmic reticulum and Golgi complex. A second type of promyelocyte, which was at an early stage of development, lacked myeloperoxidase in its secretory apparatus. These cells contained two species of azurophil granules, the first of which was devoid of peroxidase activity whereas the other reacted positively. These observations suggest that the premature arrest of myeloperoxidase synthesis in the promyelocytes from a preleukaemic patient may give rise to several populations of circulating neutrophils which can exhibit varying contents of myeloperoxidase.", "contents": "Partial myeloperoxidase deficiency in a case of preleukaemia. I. Studies of fine structure and peroxidase synthesis of promyelocytes. The ultrastructural localization of peroxidase activity has been studied in the circulating neutrophils and in a neutrophilic series of bone marrow cells from a patient with preleukaemia. Light microscopic examination showed 36% of the polymorphonuclear leucocytes to be totally devoid of myeloperoxidase, while 50% were normally stained and 14% were slightly positive for this enzyme. Electron microscopic studies revealed considerable heterogeneity in the promyelocyte population, since the number of peroxidase-deficient azurophil granules was seen to vary from 0 to 100% in these cells. Thus, several types of promyelocytes were identified. One cell type, which resembled that seen in normal subjects, contained myeloperoxidase within its azurophil granules and also within the cisternae of the rough endoplasmic reticulum and Golgi complex. A second type of promyelocyte, which was at an early stage of development, lacked myeloperoxidase in its secretory apparatus. These cells contained two species of azurophil granules, the first of which was devoid of peroxidase activity whereas the other reacted positively. These observations suggest that the premature arrest of myeloperoxidase synthesis in the promyelocytes from a preleukaemic patient may give rise to several populations of circulating neutrophils which can exhibit varying contents of myeloperoxidase."} {"id": "PMID:172112", "title": "Partial myeloperoxidase deficiency in a case of preleukaemia. II. Defects of degranulation and abnormal bactericidal activity of blood neutrophils.", "content": "A patient with a refractory anaemia preceding acute myeloblastic leukaemia had an increased susceptibility to infection due to Staphylococcus aureus. 36% of neutrophils lacked myeloperoxidase (MPO) activity and, in vitro, these polymorphonuclear neutrophils (PMN) had a defect of bactericidal activity against Staphylococcus aureus. Cytochemical studies of phagocytosis with the electron miscroscope have shown that the degranulation of primary granules (MPO+ or MPO-) was normal after phagocytosis of Escherichia coli which were normally lysed. A defective destruction of Staphylococcus aureus and Candida albicans was observed in some PMN with or without MPO activity, suggesting that MPO deficiency itself was not the only cause of this defect. In PMN which appeared normal, most MPO(+) granules were unable to fuse with the phagocytic vacuole containing intact germs even after 90 min of contact. There was, therefore, in addition to a partial MPO deficiency, a defect in cellular degranulation. This defect, the mechanism of which is unknown, may be in part responsible for the defective bacterial degradation.", "contents": "Partial myeloperoxidase deficiency in a case of preleukaemia. II. Defects of degranulation and abnormal bactericidal activity of blood neutrophils. A patient with a refractory anaemia preceding acute myeloblastic leukaemia had an increased susceptibility to infection due to Staphylococcus aureus. 36% of neutrophils lacked myeloperoxidase (MPO) activity and, in vitro, these polymorphonuclear neutrophils (PMN) had a defect of bactericidal activity against Staphylococcus aureus. Cytochemical studies of phagocytosis with the electron miscroscope have shown that the degranulation of primary granules (MPO+ or MPO-) was normal after phagocytosis of Escherichia coli which were normally lysed. A defective destruction of Staphylococcus aureus and Candida albicans was observed in some PMN with or without MPO activity, suggesting that MPO deficiency itself was not the only cause of this defect. In PMN which appeared normal, most MPO(+) granules were unable to fuse with the phagocytic vacuole containing intact germs even after 90 min of contact. There was, therefore, in addition to a partial MPO deficiency, a defect in cellular degranulation. This defect, the mechanism of which is unknown, may be in part responsible for the defective bacterial degradation."} {"id": "PMID:172113", "title": "Sodium periodate modification of factor VIII procoagulant activity.", "content": "Chemical treatment of human factor VIII by sodium periodate resulted in increased levels of procoagulant activity when measured by the two-stage assay. Increased levels of factor-VIII activity were observed following periodate treatment of factor-VII concentrates and normal, haemophilic and von Willebrand's disease plasmas. However, sodium periodate treatment of haemophilic plasmas which were completely deficient in factor-VIII activity did not cause any reduction in the clotting times of two-stage assays. No increase in procoagulant activity following oxidation of factor VIII could be detected by the one-stage assay method. Gel filtration of factor-VIII concentrates before periodate treatment showed that the protein exhibiting factor-VIII activity had an apparent molecular weight in excess of 1 000 000, whilst after periodate treatment the apparent molecular weight was reduced to 690 000.", "contents": "Sodium periodate modification of factor VIII procoagulant activity. Chemical treatment of human factor VIII by sodium periodate resulted in increased levels of procoagulant activity when measured by the two-stage assay. Increased levels of factor-VIII activity were observed following periodate treatment of factor-VII concentrates and normal, haemophilic and von Willebrand's disease plasmas. However, sodium periodate treatment of haemophilic plasmas which were completely deficient in factor-VIII activity did not cause any reduction in the clotting times of two-stage assays. No increase in procoagulant activity following oxidation of factor VIII could be detected by the one-stage assay method. Gel filtration of factor-VIII concentrates before periodate treatment showed that the protein exhibiting factor-VIII activity had an apparent molecular weight in excess of 1 000 000, whilst after periodate treatment the apparent molecular weight was reduced to 690 000."} {"id": "PMID:172115", "title": "Primary carcinoma of stomach with uterine metastasis.", "content": "Curettings from a 42-year-old woman who suffered from heartburn, weight loss and irregular vaginal bleeding showed apparently metastatic mucoid adenocarcinoma in the endocervix. The primary site of tumour was not evident. At laparotomy a gastric adenocarcinoma was found and total hysterectomy with bilateral salpingo-oophorectomy and partial gastrectomy were performed. Histological examination showed a diffuse mucoid adenocarcinoma of stomach with metastases to lymph nodes, uterine body, cervix and one ovary. The literature about metastasis of extragenital cancer to the uterus is reviewed and possible mechanisms are discussed.", "contents": "Primary carcinoma of stomach with uterine metastasis. Curettings from a 42-year-old woman who suffered from heartburn, weight loss and irregular vaginal bleeding showed apparently metastatic mucoid adenocarcinoma in the endocervix. The primary site of tumour was not evident. At laparotomy a gastric adenocarcinoma was found and total hysterectomy with bilateral salpingo-oophorectomy and partial gastrectomy were performed. Histological examination showed a diffuse mucoid adenocarcinoma of stomach with metastases to lymph nodes, uterine body, cervix and one ovary. The literature about metastasis of extragenital cancer to the uterus is reviewed and possible mechanisms are discussed."} {"id": "PMID:172116", "title": "Mechanism and specificity of rhodopsin phosphorylation.", "content": "Partial separation of protein kinase activity from rhodopsin in isolated bovine retinal photoreceptor outer segments was accomplished by mild ultrasonic treatment followed by ultracentrifugation. Residual kinase activity in the rhodopsin-rich sediment was destroyed by chemical denaturation which did not affect the spectral properties of the rhodopsin. The retinal outer segment kinase was found to be specific for rhodopsin, since in these preparations it alone of several bovine protein kinases was capable of phosphorylating rhodopsin in the light. The phosphorylation reaction apparently requires a specific conformation of the rhodopsin molecule since it is abolished by heat denaturation of rhodopsin, and it is greatly reduced or abolished by treatment of the visual pigment protein with potassium alum after the rhodopsin has been \"bleached\" by light. When kinase and rhodopsin or opsin fractions were prepared from dark-adapted and bleached outer segments and the resultant fractions were mixed in various combinations of bleached and unbleached preparations, the observed pattern of light-activated phosphorylation was consistent only with the interpretation that a conformational change in the rhodopsin molecule in the light exposes a site on the visual pigment protein to the kinase and ATP. These results rule out the possibility of a direct or indirect (rhodopsin-mediated) light activation of the kinase. Finally, phosphorylation of retinal outer segment protein in monochromatic lights of various wavelengths followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that both rhodopsin and the higher molecular weight visual pigment protein reported by several laboratories have the same action spectrum for phosphorylation. This result is consistent with the suggestion that the higher molecular weight species is a rhodopsin dimer.", "contents": "Mechanism and specificity of rhodopsin phosphorylation. Partial separation of protein kinase activity from rhodopsin in isolated bovine retinal photoreceptor outer segments was accomplished by mild ultrasonic treatment followed by ultracentrifugation. Residual kinase activity in the rhodopsin-rich sediment was destroyed by chemical denaturation which did not affect the spectral properties of the rhodopsin. The retinal outer segment kinase was found to be specific for rhodopsin, since in these preparations it alone of several bovine protein kinases was capable of phosphorylating rhodopsin in the light. The phosphorylation reaction apparently requires a specific conformation of the rhodopsin molecule since it is abolished by heat denaturation of rhodopsin, and it is greatly reduced or abolished by treatment of the visual pigment protein with potassium alum after the rhodopsin has been \"bleached\" by light. When kinase and rhodopsin or opsin fractions were prepared from dark-adapted and bleached outer segments and the resultant fractions were mixed in various combinations of bleached and unbleached preparations, the observed pattern of light-activated phosphorylation was consistent only with the interpretation that a conformational change in the rhodopsin molecule in the light exposes a site on the visual pigment protein to the kinase and ATP. These results rule out the possibility of a direct or indirect (rhodopsin-mediated) light activation of the kinase. Finally, phosphorylation of retinal outer segment protein in monochromatic lights of various wavelengths followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that both rhodopsin and the higher molecular weight visual pigment protein reported by several laboratories have the same action spectrum for phosphorylation. This result is consistent with the suggestion that the higher molecular weight species is a rhodopsin dimer."} {"id": "PMID:172117", "title": "The subunit structure of the cytochrome c oxidase complex.", "content": "The subunit structure of the cytochrome c oxidase complex has been obtained for three preparations each isolated by a different detergent procedure. Six polypeptides were present in all samples with the following molecular weights: subunits I, 36000; II, 22500, III, 17100; IV, 12500; V, 9700; and VI, 5300. These subunits have been purified by gel filtration in sodium dodecyl sulfate or in 6 M guanidine hydrochloride and their amino acid compositions have been determined. Subunit I is hydrophobic in character with a polarity of 35.7%. Subunits II through VI are more hydrophilic with polarities of 45.5, 48.6, 47.8, 49.7, and 53.7%, respectively.", "contents": "The subunit structure of the cytochrome c oxidase complex. The subunit structure of the cytochrome c oxidase complex has been obtained for three preparations each isolated by a different detergent procedure. Six polypeptides were present in all samples with the following molecular weights: subunits I, 36000; II, 22500, III, 17100; IV, 12500; V, 9700; and VI, 5300. These subunits have been purified by gel filtration in sodium dodecyl sulfate or in 6 M guanidine hydrochloride and their amino acid compositions have been determined. Subunit I is hydrophobic in character with a polarity of 35.7%. Subunits II through VI are more hydrophilic with polarities of 45.5, 48.6, 47.8, 49.7, and 53.7%, respectively."} {"id": "PMID:172118", "title": "Requirement for protein synthesis in the regulation of protein breakdown in cultured hepatoma cells.", "content": "The modes of action of insulin and of inhibitors of protein synthesis on the degradation of labeled cellular proteins have been studied in cultured hepatoma (HTC) cells. Protein breakdown is accelerated upon the deprivation of serum (normally present in the culture medium), and this enhancement is inhibited by either insulin or cycloheximide. An exception is a limited class of rapidly turning over cellular proteins, the degradation of which is not influenced by insulin or cycloheximide. Alternative hypotheses to explain the relationship of protein synthesis to the regulation of protein breakdown, viz., control by the levels of precursors of protein synthesis, regulation by the state of the ribosome cycle, or requirement for a product of protein synthesis, have been examined. Protein breakdown was not influenced by amino acid deprivation, and measurements of valyl-tRNA levels in HTC cells subjected to various experimental conditions showed no correlation between the levels of charged tRNAVal and the rates of protein degradation. Three different inhibitors of protein synthesis (puromycin, pactamycin, and cycloheximide) suppressed enhanced protein breakdown in a similar fashion. A direct relationship was found between the respective potencies of these drugs to inhibit protein synthesis and to block enhanced protein breakdown. When cycloheximide and insulin were added following a prior incubation of HTC cells in a serum-free medium, protein breakdown was maximally suppressed within 15-30 min. Actinomycin D inhibited protein breakdown only after a time lag of about 90 min. It is suggested that the regulation of protein breakdown in hepatoma cells requires the continuous formation of a product of protein synthesis, in a manner analogous to the mode of the control of this process in bacteria.", "contents": "Requirement for protein synthesis in the regulation of protein breakdown in cultured hepatoma cells. The modes of action of insulin and of inhibitors of protein synthesis on the degradation of labeled cellular proteins have been studied in cultured hepatoma (HTC) cells. Protein breakdown is accelerated upon the deprivation of serum (normally present in the culture medium), and this enhancement is inhibited by either insulin or cycloheximide. An exception is a limited class of rapidly turning over cellular proteins, the degradation of which is not influenced by insulin or cycloheximide. Alternative hypotheses to explain the relationship of protein synthesis to the regulation of protein breakdown, viz., control by the levels of precursors of protein synthesis, regulation by the state of the ribosome cycle, or requirement for a product of protein synthesis, have been examined. Protein breakdown was not influenced by amino acid deprivation, and measurements of valyl-tRNA levels in HTC cells subjected to various experimental conditions showed no correlation between the levels of charged tRNAVal and the rates of protein degradation. Three different inhibitors of protein synthesis (puromycin, pactamycin, and cycloheximide) suppressed enhanced protein breakdown in a similar fashion. A direct relationship was found between the respective potencies of these drugs to inhibit protein synthesis and to block enhanced protein breakdown. When cycloheximide and insulin were added following a prior incubation of HTC cells in a serum-free medium, protein breakdown was maximally suppressed within 15-30 min. Actinomycin D inhibited protein breakdown only after a time lag of about 90 min. It is suggested that the regulation of protein breakdown in hepatoma cells requires the continuous formation of a product of protein synthesis, in a manner analogous to the mode of the control of this process in bacteria."} {"id": "PMID:172119", "title": "Kinetics of hydrogen-deuterium exchange in adenosine 5'-monophosphate, adenosine 3':5'-monophosphate, and poly(riboadenylic acid) determined by laser-Raman spectroscopy.", "content": "Pseudo-first-order rate constants governing the deuterium exchange of 8-CH groups in adenosine 5'-monophosphate, adenosine 3':5'-monophosphate, and poly(riboadenylic acid) (poly(rA)) were determined as a function of temperature in the range 20-90 degrees C by means of laser-Raman spectroscopy. For 5'-rAMP, the logarithm of the rate constant exhibits a strictly linear dependence on reciprocal temperature, i.e., kpsi = Ae-Ea/RT, with A = 2.3 X 10(14) hr-1 and Ea = 24.2 +/- 0.6 kcal/mol. For cAMP, above 50 degrees C, kpsi is nearly identical in magnitude and temperature dependence to that of 5'-rAMP. However, below 50 degrees C, isotope exchange in cAMP is much more rapid than in 5'-rAMP, characterized by a lower activation energy (17.7 kcal/mol) and frequency factor (9.6 X 10(9) hr-1). Exchange in poly(rA) is considerably slower than in 5'-rAMP at all temperatures, but like cAMP the in k vs. 1/T plot may be divided into high temperature and low temperature domains, each characterized by different Arrhenius parameters. Above 60 degrees C, poly(rA) gives Ea = 22.0 kcal/mol and A = 3.2 X 10(12) hr-1, while below 60 degrees C, Ea = 27.7 kcal/mol and A = 1.8 X 10(16) hr-1. Thus, increasing the temperature above 60 degrees C does not diminish the retardation of exchange in poly(rA) vis a vis 5'-rAMP. These results indicate that the distribution of electrons in the adenine ring of cAMP is altered by lowering the temperature below 50 degrees C, although no similar perturbation occurs for 5'-rAMP. Retardation of exchange in poly(rA) is most probably due to base stacking at lower temperatures and to steric hindrance from the ribopolymer backbone at higher temperatures. We also report the spectral effects of deuterium exchange on the vibrational Raman frequencies of 5'-rAMP, cAMP, and poly(rA) and suggest a number of new assignments for the 5' and cyclic ribosyl phosphate groups.", "contents": "Kinetics of hydrogen-deuterium exchange in adenosine 5'-monophosphate, adenosine 3':5'-monophosphate, and poly(riboadenylic acid) determined by laser-Raman spectroscopy. Pseudo-first-order rate constants governing the deuterium exchange of 8-CH groups in adenosine 5'-monophosphate, adenosine 3':5'-monophosphate, and poly(riboadenylic acid) (poly(rA)) were determined as a function of temperature in the range 20-90 degrees C by means of laser-Raman spectroscopy. For 5'-rAMP, the logarithm of the rate constant exhibits a strictly linear dependence on reciprocal temperature, i.e., kpsi = Ae-Ea/RT, with A = 2.3 X 10(14) hr-1 and Ea = 24.2 +/- 0.6 kcal/mol. For cAMP, above 50 degrees C, kpsi is nearly identical in magnitude and temperature dependence to that of 5'-rAMP. However, below 50 degrees C, isotope exchange in cAMP is much more rapid than in 5'-rAMP, characterized by a lower activation energy (17.7 kcal/mol) and frequency factor (9.6 X 10(9) hr-1). Exchange in poly(rA) is considerably slower than in 5'-rAMP at all temperatures, but like cAMP the in k vs. 1/T plot may be divided into high temperature and low temperature domains, each characterized by different Arrhenius parameters. Above 60 degrees C, poly(rA) gives Ea = 22.0 kcal/mol and A = 3.2 X 10(12) hr-1, while below 60 degrees C, Ea = 27.7 kcal/mol and A = 1.8 X 10(16) hr-1. Thus, increasing the temperature above 60 degrees C does not diminish the retardation of exchange in poly(rA) vis a vis 5'-rAMP. These results indicate that the distribution of electrons in the adenine ring of cAMP is altered by lowering the temperature below 50 degrees C, although no similar perturbation occurs for 5'-rAMP. Retardation of exchange in poly(rA) is most probably due to base stacking at lower temperatures and to steric hindrance from the ribopolymer backbone at higher temperatures. We also report the spectral effects of deuterium exchange on the vibrational Raman frequencies of 5'-rAMP, cAMP, and poly(rA) and suggest a number of new assignments for the 5' and cyclic ribosyl phosphate groups."} {"id": "PMID:172120", "title": "Activation of liver alcohol dehydrogenases by imidoesters generated in solution.", "content": "Various omega-halogenated carboxy acids and amides were evaluated as potential active-site-directed reagents for alcohol dehydrogenase. 2-Bromoacetamide and bromoacetic and 3-bromopropionic acids inactivated the enzyme; AMP, NAD+, and NADH markedly decreased the rate of inactivation. Some omega-halogenated carboxyamides, X(CH2)nCONH2, increased the activity of the enzyme with the rate and extent of activation depending on the number of methylene units (n) in the order 3 greater than 4 greater than 2 and on X in the order Br greater than Cl. 4-Chlorobutyramide (0.1 M) activated the horse liver enzyme 20-fold in 24 hr at pH 8.0 and 25 degrees. The activation was not prevented by AMP or 2,2-bipyridine, but was by NADH. The kinetic constants and turnover numbers for human and horse liver alcohol dehydrogenases treated with chlorobutyramide were increased markedly compared to those for native enzymes. Alcohol dehydrogenase treated with chlorobutyramide was not further activated by methyl picolinimidate, an imidoester which activates native enzyme by modifying amino groups in the active sites. Chlorobutyramide does not appear to react directly with the enzyme but cyclizes in the reaction medium to form an intermediate imidoester, 2-iminotetrahydrofuran, which reacts with most of the amino groups of the enzyme.", "contents": "Activation of liver alcohol dehydrogenases by imidoesters generated in solution. Various omega-halogenated carboxy acids and amides were evaluated as potential active-site-directed reagents for alcohol dehydrogenase. 2-Bromoacetamide and bromoacetic and 3-bromopropionic acids inactivated the enzyme; AMP, NAD+, and NADH markedly decreased the rate of inactivation. Some omega-halogenated carboxyamides, X(CH2)nCONH2, increased the activity of the enzyme with the rate and extent of activation depending on the number of methylene units (n) in the order 3 greater than 4 greater than 2 and on X in the order Br greater than Cl. 4-Chlorobutyramide (0.1 M) activated the horse liver enzyme 20-fold in 24 hr at pH 8.0 and 25 degrees. The activation was not prevented by AMP or 2,2-bipyridine, but was by NADH. The kinetic constants and turnover numbers for human and horse liver alcohol dehydrogenases treated with chlorobutyramide were increased markedly compared to those for native enzymes. Alcohol dehydrogenase treated with chlorobutyramide was not further activated by methyl picolinimidate, an imidoester which activates native enzyme by modifying amino groups in the active sites. Chlorobutyramide does not appear to react directly with the enzyme but cyclizes in the reaction medium to form an intermediate imidoester, 2-iminotetrahydrofuran, which reacts with most of the amino groups of the enzyme."} {"id": "PMID:172121", "title": "Activation of acetyl- and butyrylcholinesterase by enzymatic removal of sialic acid from intact neuroblastoma and astroblastoma cells in culture.", "content": "Removal of sialic acid from intact mammalian nervous system cells in tissue culture is accompanied by an immediate increase in cellular cholinesterase activity. Treatment of hamster astroblast cells (clonal line NN) and mouse neuroblastoma cells (clonal lines S21, N18, and N115) for brief periods with a low level of Clostridium perfringens sialidase, 5 X 10(-3) units/ml, removed 1-15 mug of sialic acid per mg of cell protein and brought about a large increase in v0 and Vmax of cellular acetylcholinesterase (EC 3.1.1.7). Butyrylcholinesterase (EC 3.1.1.8) activities also increased upon careful enzymatic removal of cellular sialic acid, and cells with characteristically low butyrylcholinesterase activity, e.g., adrenergic clonal line N115 neuroblasts displayed relatively high activity after treatment with sialidase. These findings open the possibility that adaptive regulation of cholinesterases in mammalian cells may be mediated rapidly through changes in their sialic acid content.", "contents": "Activation of acetyl- and butyrylcholinesterase by enzymatic removal of sialic acid from intact neuroblastoma and astroblastoma cells in culture. Removal of sialic acid from intact mammalian nervous system cells in tissue culture is accompanied by an immediate increase in cellular cholinesterase activity. Treatment of hamster astroblast cells (clonal line NN) and mouse neuroblastoma cells (clonal lines S21, N18, and N115) for brief periods with a low level of Clostridium perfringens sialidase, 5 X 10(-3) units/ml, removed 1-15 mug of sialic acid per mg of cell protein and brought about a large increase in v0 and Vmax of cellular acetylcholinesterase (EC 3.1.1.7). Butyrylcholinesterase (EC 3.1.1.8) activities also increased upon careful enzymatic removal of cellular sialic acid, and cells with characteristically low butyrylcholinesterase activity, e.g., adrenergic clonal line N115 neuroblasts displayed relatively high activity after treatment with sialidase. These findings open the possibility that adaptive regulation of cholinesterases in mammalian cells may be mediated rapidly through changes in their sialic acid content."} {"id": "PMID:172122", "title": "The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: chemiluminescence and peroxidation.", "content": "Reaction of bovine erythrocyte superoxide dismutase with H2O2 was accompanied by a luminescence whose intensity was a function of the concentration of H2O2 and whose duration was coincident with the inactivation of the enzyme by this reagent. Oxygen, which protected against inactivation, also diminished the luminescence. Several other compounds which prevented the inactivation by H2O2 also modified the luminescence. Thus urate, formate, and triethylamine inhibited luminescence whereas imidazole and xanthine augmented it. These seemingly contrary effects can be explained by assuming that the compounds which protected the enzyme were peroxidized in competition with the sensitive group on the enzyme. The luminescence arises because that group on the enzyme was oxidized to a product in an electronically excited state, which could return to the ground state by emitting light. Imidazole and xanthine gave electronically excited products whose quantum efficiency was greater than that of the group on the enzyme, whereas urate, formate, and triethylamine gave products with much lower luminescent efficiencies. This superoxide dismutase could catalyze the peroxidation of a wide range of compounds, including ferrocytochrome c, luminol, diphenylisobenzofuran, dianisidine, and linoleic acid. In control experiments, boiled enzyme was inactive. This peroxidative activity can lead to unexpected effects when superoxide dismutase is added to H2O2-producing systems, as a probe for the involvement of O2-. Several examples from the literature are cited to illustrate the misinterpretations which this previously unrecognized peroxidative activity can generate.", "contents": "The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: chemiluminescence and peroxidation. Reaction of bovine erythrocyte superoxide dismutase with H2O2 was accompanied by a luminescence whose intensity was a function of the concentration of H2O2 and whose duration was coincident with the inactivation of the enzyme by this reagent. Oxygen, which protected against inactivation, also diminished the luminescence. Several other compounds which prevented the inactivation by H2O2 also modified the luminescence. Thus urate, formate, and triethylamine inhibited luminescence whereas imidazole and xanthine augmented it. These seemingly contrary effects can be explained by assuming that the compounds which protected the enzyme were peroxidized in competition with the sensitive group on the enzyme. The luminescence arises because that group on the enzyme was oxidized to a product in an electronically excited state, which could return to the ground state by emitting light. Imidazole and xanthine gave electronically excited products whose quantum efficiency was greater than that of the group on the enzyme, whereas urate, formate, and triethylamine gave products with much lower luminescent efficiencies. This superoxide dismutase could catalyze the peroxidation of a wide range of compounds, including ferrocytochrome c, luminol, diphenylisobenzofuran, dianisidine, and linoleic acid. In control experiments, boiled enzyme was inactive. This peroxidative activity can lead to unexpected effects when superoxide dismutase is added to H2O2-producing systems, as a probe for the involvement of O2-. Several examples from the literature are cited to illustrate the misinterpretations which this previously unrecognized peroxidative activity can generate."} {"id": "PMID:172123", "title": "Inactivation of rabbit, pig, and carp adenylate kinases by N6-o- and p-fluorobenzoyladenosine 5'-triphosphates.", "content": "N6-O- and p-fluorobenzoyladenosine 5'-triphosphates (IIIc and IIc, respectively) have been synthesized as potential adenosine 5'-triphosphate (ATP) site-directed reagents for enzymes. IIc and IIIc were substrates of yeast hexokinase; neither they nor the corresponding ADP derivatives inactivated yeast hexokinase or rabbit pyruvate kinase. IIc rapidly inactivated rabbit and carp muscle adenylate kinases; the effect is probably ATP site directed because N6-benzoyl-ATP did not inactivate and was a substrate (Vmax = 28 and 10%, respectively, that of ATP), and because of ATP retarded the inactivation. The inactivations followed pseudo-firsr-order kinetics; in the presence of 2.64 mM ATP at 0 degrees the half-life of the rabbit kinase was 210 min with 50 muM IIc and the half-life of the carp kinase was 130 min with 100 muM IIc. Adenylate kinase of pig muscle was inactivated by IIc in a manner similar to the rabbit and carp enzymes except that the rate of inactivation exhibited an inflexion. IIIc inactivated rabbit, pig, and carp adenylate kinases by pseudo-first-order kinetics; the rate constants for inactivation at 0 degrees were 9.1 X 10(-3), 1.3 X 10(-3), and 1.9 X 10(-3) min-1 and the apparent dissociation constants (K) of the IIIc-enzyme complexes were 710, 970, and 720 muM, respectively. From the substrate properties of IIIc alone and in admixture with ATP its dissociation constants (Ki) from the ATP sites of the enzymes were found to be 500, 700, and 845 muM, respectively. The similarity between the K and Ki values, together with marked retardation of the inactivations by ATP, indicates that IIIc is an ATP-site-directed reagent for the three adenylate kinases.", "contents": "Inactivation of rabbit, pig, and carp adenylate kinases by N6-o- and p-fluorobenzoyladenosine 5'-triphosphates. N6-O- and p-fluorobenzoyladenosine 5'-triphosphates (IIIc and IIc, respectively) have been synthesized as potential adenosine 5'-triphosphate (ATP) site-directed reagents for enzymes. IIc and IIIc were substrates of yeast hexokinase; neither they nor the corresponding ADP derivatives inactivated yeast hexokinase or rabbit pyruvate kinase. IIc rapidly inactivated rabbit and carp muscle adenylate kinases; the effect is probably ATP site directed because N6-benzoyl-ATP did not inactivate and was a substrate (Vmax = 28 and 10%, respectively, that of ATP), and because of ATP retarded the inactivation. The inactivations followed pseudo-firsr-order kinetics; in the presence of 2.64 mM ATP at 0 degrees the half-life of the rabbit kinase was 210 min with 50 muM IIc and the half-life of the carp kinase was 130 min with 100 muM IIc. Adenylate kinase of pig muscle was inactivated by IIc in a manner similar to the rabbit and carp enzymes except that the rate of inactivation exhibited an inflexion. IIIc inactivated rabbit, pig, and carp adenylate kinases by pseudo-first-order kinetics; the rate constants for inactivation at 0 degrees were 9.1 X 10(-3), 1.3 X 10(-3), and 1.9 X 10(-3) min-1 and the apparent dissociation constants (K) of the IIIc-enzyme complexes were 710, 970, and 720 muM, respectively. From the substrate properties of IIIc alone and in admixture with ATP its dissociation constants (Ki) from the ATP sites of the enzymes were found to be 500, 700, and 845 muM, respectively. The similarity between the K and Ki values, together with marked retardation of the inactivations by ATP, indicates that IIIc is an ATP-site-directed reagent for the three adenylate kinases."} {"id": "PMID:172124", "title": "Uridine diphosphate glucose synthase from calf liver: determinants of enzyme activity in vitro.", "content": "The reaction catalyzed by calf liver uridine diphosphate glucose synthase (pyrophosphorylase) (EC 2.7.7.9; UTP + glucose 1-phosphate = UDP-glucose + PPi) is an example of an enzymic reaction in which a nucleoside triphosphate other than ATP is the immediate source of metabolic energy. Kinetic properties of the enzyme, acting in the direction of UCP-glucose formation were investigated in vitro. The reaction was inhibited by UDP-glucose (0.072), Pi (11), UDP (1.6), UDP-xylose (0.87), UDP-glucuronate (1.3), and UDP-galacturonate (0.95). The numbers in parentheses indicate the concentration (mM) required for half-maximal inhibition under the conditions used. Other compounds tested, including ATP, ADP, and AMP, had no effect. Over a range of concentrations of UTP (0.04-0.8 MM) and UDP-glucose (0.05-0.03 mM), the reaction rate was more dependent on the concentration ratio [UDP-glucose]/[UTP] than on the absolute concentration of either compound. Comparison of the kinetic properties in vitro with estimates of metabolite levels in vivo suggests that (1) the enzyme operates in a range far from its maximal rate, and (2) the concentrations of glucose 1-phosphate and Pi and the ratio [UDP-glucose]/[UTP] may be the most important determinants of UDP-glucose synthase activity.", "contents": "Uridine diphosphate glucose synthase from calf liver: determinants of enzyme activity in vitro. The reaction catalyzed by calf liver uridine diphosphate glucose synthase (pyrophosphorylase) (EC 2.7.7.9; UTP + glucose 1-phosphate = UDP-glucose + PPi) is an example of an enzymic reaction in which a nucleoside triphosphate other than ATP is the immediate source of metabolic energy. Kinetic properties of the enzyme, acting in the direction of UCP-glucose formation were investigated in vitro. The reaction was inhibited by UDP-glucose (0.072), Pi (11), UDP (1.6), UDP-xylose (0.87), UDP-glucuronate (1.3), and UDP-galacturonate (0.95). The numbers in parentheses indicate the concentration (mM) required for half-maximal inhibition under the conditions used. Other compounds tested, including ATP, ADP, and AMP, had no effect. Over a range of concentrations of UTP (0.04-0.8 MM) and UDP-glucose (0.05-0.03 mM), the reaction rate was more dependent on the concentration ratio [UDP-glucose]/[UTP] than on the absolute concentration of either compound. Comparison of the kinetic properties in vitro with estimates of metabolite levels in vivo suggests that (1) the enzyme operates in a range far from its maximal rate, and (2) the concentrations of glucose 1-phosphate and Pi and the ratio [UDP-glucose]/[UTP] may be the most important determinants of UDP-glucose synthase activity."} {"id": "PMID:172126", "title": "Rotational correlation times and partition coefficients of a spin label solute in lecithin vesicles.", "content": "Di-tert-butylnitroxide dissolved in an aqueous suspension of egg yolk lecithin vesicles is distributed between the two phases. Partition coefficients of the nitroxide between the lipid and the water, calculated from the nitroxide electron paramagnetic resonance (EPR) spectra, decrease with decreasing temperature until approximately the freezing point of the solvent. Below this temperature the nitroxide is detected only in the lecithin. The rotational correlation times of the spin label present in the lecithin were calculated for the temperature range from +45 to -60 degrees C. At low temperatures, the EPR spectra are characteristic of a superposition of two spectra resulting from the nitroxide dissolved in the lipid in two environments with different rotational correlation times.", "contents": "Rotational correlation times and partition coefficients of a spin label solute in lecithin vesicles. Di-tert-butylnitroxide dissolved in an aqueous suspension of egg yolk lecithin vesicles is distributed between the two phases. Partition coefficients of the nitroxide between the lipid and the water, calculated from the nitroxide electron paramagnetic resonance (EPR) spectra, decrease with decreasing temperature until approximately the freezing point of the solvent. Below this temperature the nitroxide is detected only in the lecithin. The rotational correlation times of the spin label present in the lecithin were calculated for the temperature range from +45 to -60 degrees C. At low temperatures, the EPR spectra are characteristic of a superposition of two spectra resulting from the nitroxide dissolved in the lipid in two environments with different rotational correlation times."} {"id": "PMID:172127", "title": "Quantitative aspects of hormone-receptor interactions of high affinity. Effect of receptor concentration and measurement of dissociation constants of labeled and unlabeled hormones.", "content": "It is demonstrated that because of limitations in the magnitude of the specific activity of radiolabeled hormone derivatives, direct binding studies of hormone-receptor interactions of high affinity (10(-9) -10(-11) M, depending on whether 3H- or 123I-labeled hormones are used) will be subject to artifactual distortions due to the need to utilize high concentrations of the receptor. If the concentration of the receptor is not ten times lower than the true affinity constant, the apparent dissociation constant obtained from direct concentration binding curves will vary as a linear function of the receptor concentration. In addition, at high receptor concentrations saturability becomes difficult to demonstrate experimentally and the binding data yield apparently non-hyperbolic, sigmoidal curves which can be mistakenly interpreted to depict cooperative interactions. Similar artifacts related to receptor concentration are predicted for measurements of the hormone concentration dependence of biological proce-ses (e.g. activation of adenylate cyclase, transport processes, etc.). Methods for detecting these effects, and correctly measuring affinities for labeled and unlabeled hormones under these conditions, are described. The implications for measuring the binding properties of hormone-receptor interactions are discussed, especially in reference to studies of the comparative analysis of receptor function in altered metabolic states and to studies relating the biological and binding properties of hormones.", "contents": "Quantitative aspects of hormone-receptor interactions of high affinity. Effect of receptor concentration and measurement of dissociation constants of labeled and unlabeled hormones. It is demonstrated that because of limitations in the magnitude of the specific activity of radiolabeled hormone derivatives, direct binding studies of hormone-receptor interactions of high affinity (10(-9) -10(-11) M, depending on whether 3H- or 123I-labeled hormones are used) will be subject to artifactual distortions due to the need to utilize high concentrations of the receptor. If the concentration of the receptor is not ten times lower than the true affinity constant, the apparent dissociation constant obtained from direct concentration binding curves will vary as a linear function of the receptor concentration. In addition, at high receptor concentrations saturability becomes difficult to demonstrate experimentally and the binding data yield apparently non-hyperbolic, sigmoidal curves which can be mistakenly interpreted to depict cooperative interactions. Similar artifacts related to receptor concentration are predicted for measurements of the hormone concentration dependence of biological proce-ses (e.g. activation of adenylate cyclase, transport processes, etc.). Methods for detecting these effects, and correctly measuring affinities for labeled and unlabeled hormones under these conditions, are described. The implications for measuring the binding properties of hormone-receptor interactions are discussed, especially in reference to studies of the comparative analysis of receptor function in altered metabolic states and to studies relating the biological and binding properties of hormones."} {"id": "PMID:172128", "title": "Redox state of respiratory chain enzymes and potassium transport in silkworm mid-gut.", "content": "The midgut of Hyalophora cecropia actively transports potassium from hemolymph to lumen and the energy for this process appears to be intimately linked to oxidative metabolism. In the present investigation, we monitored concurrently the rate of active transport and the redox levels of the components of the respiratory chain in the intact tissue under a variety of experimental conditions. Approximately equal concentrations of cytochromes a3, a, c and b-557 were found. Other investigators (Pappenheimer, Jr, A.M. and Williams, C.M. (1954) J. Biol. Chem. 209, 915, Shappirio, D.G. and Williams, C.M. (1957) Proc. R. Soc. Lond. Ser. B 147, 233 and Chance, B. and Pappenheimer, Jr, A.M. (1957) J. Biol, Chem, 209, 931) have indentified cytochrome b-557 with b5 and found that it exists primarily in an extramitochondrial location. Steady-state experiments demonstrated that all these cytochromes were approximately 50% reduced while active transport proceeded at a high rate in regular cecropia Ringer containing 32 mM KCl. When the potassium concentration was reduced, the active transport decreased and all the cytochromes became more oxidized. Addition of 1 mM cyanide inhibited active transport by 90% and caused a 100% reduction of all cytochromes. Redox state and short circuit current (Isc) kinetics measured as the tissue was made anoxic showed that all the respiratory enzymes, except cytochrome b-557, became fully reduced at a faster rate than the rate of inhibition of the Isc. The rate of cytochrome b-557 reduction followed kinetically the Isc. These observations are interpreted in a scheme where cytochrome b-557 (possibly b5) branches off cytochrome c from the conventional resporatory chain, utilizing cytochrome a3 as the terminal oxidase for both branches. Cytochrome b-557 may be involved in providing a direct link between oxidative metabolism and active transport in the midgut of the silkworm.", "contents": "Redox state of respiratory chain enzymes and potassium transport in silkworm mid-gut. The midgut of Hyalophora cecropia actively transports potassium from hemolymph to lumen and the energy for this process appears to be intimately linked to oxidative metabolism. In the present investigation, we monitored concurrently the rate of active transport and the redox levels of the components of the respiratory chain in the intact tissue under a variety of experimental conditions. Approximately equal concentrations of cytochromes a3, a, c and b-557 were found. Other investigators (Pappenheimer, Jr, A.M. and Williams, C.M. (1954) J. Biol. Chem. 209, 915, Shappirio, D.G. and Williams, C.M. (1957) Proc. R. Soc. Lond. Ser. B 147, 233 and Chance, B. and Pappenheimer, Jr, A.M. (1957) J. Biol, Chem, 209, 931) have indentified cytochrome b-557 with b5 and found that it exists primarily in an extramitochondrial location. Steady-state experiments demonstrated that all these cytochromes were approximately 50% reduced while active transport proceeded at a high rate in regular cecropia Ringer containing 32 mM KCl. When the potassium concentration was reduced, the active transport decreased and all the cytochromes became more oxidized. Addition of 1 mM cyanide inhibited active transport by 90% and caused a 100% reduction of all cytochromes. Redox state and short circuit current (Isc) kinetics measured as the tissue was made anoxic showed that all the respiratory enzymes, except cytochrome b-557, became fully reduced at a faster rate than the rate of inhibition of the Isc. The rate of cytochrome b-557 reduction followed kinetically the Isc. These observations are interpreted in a scheme where cytochrome b-557 (possibly b5) branches off cytochrome c from the conventional resporatory chain, utilizing cytochrome a3 as the terminal oxidase for both branches. Cytochrome b-557 may be involved in providing a direct link between oxidative metabolism and active transport in the midgut of the silkworm."} {"id": "PMID:172129", "title": "Symmetry, orientation and rotational mobility in the a3 heme of cytochrome c oxidase in the inner membrane of mitochondria.", "content": "The photoinduced linear dichroism of absorption changes resulting from photolysis of the complex between heme a3 of the cytochrome oxidase and CO is studied. The experiments started from isotropic solutions or suspensions of the enzyme both in its isolated form and in mitochondria. The anisotropy responsible for the linear dichroism was induced by excitation with a flash of linearly polarized light. The dichroic ratios observed with various systems; polymerized enzyme in solution, enzyme in mitochondria and in submitochondrial particles (at 20 degrees C as well as at liquid N2-temperature) all approached a value of 4/3 which characterizes a chromophore which is circularly degenerate. Therefrom we conclude that the interaction of heme a3 with its microenvironment within the protein does not break its four-fold symmetry. The experiments with mitochondria and submitochondrial particles suspended in aqueous buffer revealed similarly high dichoric ratios without any dichroic relaxation other than a rather slow one which could be attributed to the rotation of the whole organelle in the suspending medium. Therefrom we conclude that the cytochrome oxidase either is totally immobilized in the membrane, or that it carries out only limited rotational diffusion around a single axis coinciding with the symmetry axis of heme a3. In the light of independent evidence for a transmembrane arrangement of the oxidase and for the general fluidity of the inner mitochondrial membrane we consider anisotropic mobility of the cytochrome oxidase around an axis normal to the plane of the membrane as the most likely interpretation. Then our experimental results imply that the plane of heme a3 is coplanar to the membrane.", "contents": "Symmetry, orientation and rotational mobility in the a3 heme of cytochrome c oxidase in the inner membrane of mitochondria. The photoinduced linear dichroism of absorption changes resulting from photolysis of the complex between heme a3 of the cytochrome oxidase and CO is studied. The experiments started from isotropic solutions or suspensions of the enzyme both in its isolated form and in mitochondria. The anisotropy responsible for the linear dichroism was induced by excitation with a flash of linearly polarized light. The dichroic ratios observed with various systems; polymerized enzyme in solution, enzyme in mitochondria and in submitochondrial particles (at 20 degrees C as well as at liquid N2-temperature) all approached a value of 4/3 which characterizes a chromophore which is circularly degenerate. Therefrom we conclude that the interaction of heme a3 with its microenvironment within the protein does not break its four-fold symmetry. The experiments with mitochondria and submitochondrial particles suspended in aqueous buffer revealed similarly high dichoric ratios without any dichroic relaxation other than a rather slow one which could be attributed to the rotation of the whole organelle in the suspending medium. Therefrom we conclude that the cytochrome oxidase either is totally immobilized in the membrane, or that it carries out only limited rotational diffusion around a single axis coinciding with the symmetry axis of heme a3. In the light of independent evidence for a transmembrane arrangement of the oxidase and for the general fluidity of the inner mitochondrial membrane we consider anisotropic mobility of the cytochrome oxidase around an axis normal to the plane of the membrane as the most likely interpretation. Then our experimental results imply that the plane of heme a3 is coplanar to the membrane."} {"id": "PMID:172130", "title": "ATPase complex and oxidative phosphorylation in chloramphenicol-induced megamitochondria from mouse liver.", "content": "1. Functional properties of the ATPase complex are investigated in megamitochondria isolated from livers of weanling mice fed a diet containing 2% chloramphenicol, as an inhibitor of mitochondrial protein synthesis. 2. Whereas the specific activity of ATPase remains unchanged in chloramphenicol-induced megamitochondria, about 40% of the enyzme activity is resistant to inhibition by oligomycin, triethyltin or venturicidin. It is concluded that the ATPase complex lacks one or more components whose synthesis or accumulation is dependent on mitochondrial translation. The inhibitor-resistant ATPase portion appears tightly bound to the mitochondrial membrane. 3. Respiratory chain phosphorylation is tightly coupled in isolated megamitochondria. ATP synthesis and ATP-Pi exchange are diminished by 40%, as compared to control mitochondria, but both processes are sensitive to oligomycin, triethyltin or venturicidin. 4. The decrease in ATP synthesis and ATP-Pi exchange in megamitochondria correlates quite well with the emergence of inhibitor-resistant ATPase. 5. The following electron transport activities in the megmitochondria are reduced: NADH-cytochrome c reductase, by 60%, cytochrome oxidase, by 80%; the amount of antimycin required to gain complete inhibition of the bc1-segment is diminished by more than 50%. On the other hand succinate dehydrogenase activity is increased by 50%. 6. Chloramphenicol-induced megamitochondria appear to be a useful system for studying the role of mitochondrial translation in the assembly of mammalian mitochondria.", "contents": "ATPase complex and oxidative phosphorylation in chloramphenicol-induced megamitochondria from mouse liver. 1. Functional properties of the ATPase complex are investigated in megamitochondria isolated from livers of weanling mice fed a diet containing 2% chloramphenicol, as an inhibitor of mitochondrial protein synthesis. 2. Whereas the specific activity of ATPase remains unchanged in chloramphenicol-induced megamitochondria, about 40% of the enyzme activity is resistant to inhibition by oligomycin, triethyltin or venturicidin. It is concluded that the ATPase complex lacks one or more components whose synthesis or accumulation is dependent on mitochondrial translation. The inhibitor-resistant ATPase portion appears tightly bound to the mitochondrial membrane. 3. Respiratory chain phosphorylation is tightly coupled in isolated megamitochondria. ATP synthesis and ATP-Pi exchange are diminished by 40%, as compared to control mitochondria, but both processes are sensitive to oligomycin, triethyltin or venturicidin. 4. The decrease in ATP synthesis and ATP-Pi exchange in megamitochondria correlates quite well with the emergence of inhibitor-resistant ATPase. 5. The following electron transport activities in the megmitochondria are reduced: NADH-cytochrome c reductase, by 60%, cytochrome oxidase, by 80%; the amount of antimycin required to gain complete inhibition of the bc1-segment is diminished by more than 50%. On the other hand succinate dehydrogenase activity is increased by 50%. 6. Chloramphenicol-induced megamitochondria appear to be a useful system for studying the role of mitochondrial translation in the assembly of mammalian mitochondria."} {"id": "PMID:172131", "title": "On the nature of the iron sulfur cluster in a deuterated algal ferredoxin.", "content": "A protonated and a completely deuterated two-iron algal ferredoxin from Synechococcus lividus have been studied by optical, electron paramagnetic resonance, electron-nuclear double resonance, proton magnetic resonance and Mossbauer spectroscopies; temperature dependent magnetic susceptibility measurements are reported as well. These studies have confirmed the electron localized model of the active center in the two-iron ferredoxins, as previously deduced from studies of spinach ferredoxin, have yielded much more precise spectroscopic parameters for this center, and have thus greatly increased the confidence in this model.", "contents": "On the nature of the iron sulfur cluster in a deuterated algal ferredoxin. A protonated and a completely deuterated two-iron algal ferredoxin from Synechococcus lividus have been studied by optical, electron paramagnetic resonance, electron-nuclear double resonance, proton magnetic resonance and Mossbauer spectroscopies; temperature dependent magnetic susceptibility measurements are reported as well. These studies have confirmed the electron localized model of the active center in the two-iron ferredoxins, as previously deduced from studies of spinach ferredoxin, have yielded much more precise spectroscopic parameters for this center, and have thus greatly increased the confidence in this model."} {"id": "PMID:172132", "title": "Respiratory control in isolated perfused rat heart. Role of the equilibrium relations between the mitochondrial electron carriers and the adenylate system.", "content": "The effects of KCl-induced cardiac arrest on the redox state of the fluorescent flavoproteins and nicotinamide nucleotides and on that of cytochromes c and a were studied by surface fluorometric and reflectance spectrophotometric methods. These changes were compared with measurements of the concentrations of the adenylate system, creatine phosphate, some intermediates of the tricarboxylic acid cycle and reactants of the glutamate dehydrogenase system. KCl-induced cardiac arrest caused reduction of the fluorescent flavoproteins and nicotinamide nucleotides, oxidation of cytochromes c and a, inhibition of oxygen consumption and an increase in the ATP/(ADP X Pi) ratio. The increase in the latter was due mainly to a decrease in the concentration of Pi and an equivalent increase in creatine phosphate. The cytochromes c and a were maintained at equal redox potential and changed in parallel. When the redox state of the mitochondrial NAD couple was calculated from the glutamate dehydrogenase equilibrium, the free energy change (deltaG) corresponding to the potential difference between the NAD couple and cytochrome c was 115.8 kj/mol in the beating heart and 122.2 kj/mol in the arrested heart. The deltaG values of ATP hydrolysis calculated from the concentrations of ATP, Pi and ADP, corrected for bound ADP, were 111.1 kj/2 mol and 115.4 kj/2 mol in the beating and arrested heart respectively. The accumulation of citrate and the direction of the redox changes in the respiratory carriers indicate that the tricarboxylic acid cycle flux is controlled by the respiratory chain. The data also show a near equilibrium between the electron carriers and the adenylate system and suggest that the equilibrium hypothesis of mitochondrial respiratory control is applicable to intact myocardial tissue.", "contents": "Respiratory control in isolated perfused rat heart. Role of the equilibrium relations between the mitochondrial electron carriers and the adenylate system. The effects of KCl-induced cardiac arrest on the redox state of the fluorescent flavoproteins and nicotinamide nucleotides and on that of cytochromes c and a were studied by surface fluorometric and reflectance spectrophotometric methods. These changes were compared with measurements of the concentrations of the adenylate system, creatine phosphate, some intermediates of the tricarboxylic acid cycle and reactants of the glutamate dehydrogenase system. KCl-induced cardiac arrest caused reduction of the fluorescent flavoproteins and nicotinamide nucleotides, oxidation of cytochromes c and a, inhibition of oxygen consumption and an increase in the ATP/(ADP X Pi) ratio. The increase in the latter was due mainly to a decrease in the concentration of Pi and an equivalent increase in creatine phosphate. The cytochromes c and a were maintained at equal redox potential and changed in parallel. When the redox state of the mitochondrial NAD couple was calculated from the glutamate dehydrogenase equilibrium, the free energy change (deltaG) corresponding to the potential difference between the NAD couple and cytochrome c was 115.8 kj/mol in the beating heart and 122.2 kj/mol in the arrested heart. The deltaG values of ATP hydrolysis calculated from the concentrations of ATP, Pi and ADP, corrected for bound ADP, were 111.1 kj/2 mol and 115.4 kj/2 mol in the beating and arrested heart respectively. The accumulation of citrate and the direction of the redox changes in the respiratory carriers indicate that the tricarboxylic acid cycle flux is controlled by the respiratory chain. The data also show a near equilibrium between the electron carriers and the adenylate system and suggest that the equilibrium hypothesis of mitochondrial respiratory control is applicable to intact myocardial tissue."} {"id": "PMID:172133", "title": "Water proton relaxation as a monitor of membrane-bound manganese in spinach chloroplasts.", "content": "First measurements of proton relaxation on chloroplast membranes are presented here. Experiments show that the water proton spin-lattice relaxation rate in chloroplast thylakoid membrane suspensions can be used to monitor membrane-bound manganese. The relaxation effect is reduced to 0.4 of its original value upon manganese extraction by washing with either alkaline Tris buffer or NH2OH/EDTA solution. Large increases in the proton relaxation rate are measured in the presence of reductants such as tetraphenylboron and NH2OH; oxidants such as potassium ferricyanide or 2,6-dichlorophenolindophenol lead to an decrease in this rate. These results suggest that manganese exists as a mixture of oxidation states in dark-adapted chloroplasts.", "contents": "Water proton relaxation as a monitor of membrane-bound manganese in spinach chloroplasts. First measurements of proton relaxation on chloroplast membranes are presented here. Experiments show that the water proton spin-lattice relaxation rate in chloroplast thylakoid membrane suspensions can be used to monitor membrane-bound manganese. The relaxation effect is reduced to 0.4 of its original value upon manganese extraction by washing with either alkaline Tris buffer or NH2OH/EDTA solution. Large increases in the proton relaxation rate are measured in the presence of reductants such as tetraphenylboron and NH2OH; oxidants such as potassium ferricyanide or 2,6-dichlorophenolindophenol lead to an decrease in this rate. These results suggest that manganese exists as a mixture of oxidation states in dark-adapted chloroplasts."} {"id": "PMID:172134", "title": "Phosphatidylglycerol in lung surfactant. II. Subcellular distribution and mechanism of biosynthesis in vitro.", "content": "Lamellar inclusion bodies, apparent precursors for alveolar surfactant lining, have remarkably similar phospholipid composition to surfactant from alveolar lavage, but distinctly different from other fractions studied: mitochondria, microsomal fraction containing endoplasmic reticulum membranes, plasma membranes and nuclei. Surfactant contained (as % of total phospholipid phosphate): 75.5-77.0% lecithin, 11.0-11.2% phosphatidylglycerol, 4.2-4.6% phosphatidylethanolamine, 3.0-3.2% phosphatidylinositol, 1.5-1.7% bis-(monoacylglycerol) phosphate, 1.2-1.9% phosphatidylserine, and 0.7-1.5% sphingomyelin. Fatty acids of phosphatidylglycerol from lamellar bodies were similar to those from microsomes but different from those in mitochondria. Lung homogenate in continuous sucrose density gradient displayed two major activity peaks of phosphatidylglycerol synthesis: the heavier from mitochondria; the lighter from endoplasmic reticulum. Studies on mechanism of phosphatidylglycerol synthesis in vitro revealed (in these two fractions) CDP-diglyceride and sn-glycerol phosphate precursors to phosphatidylglycerol phosphate, that hydrolysed to phosphatidylglycerol. In microsomes disaturated CDP-diglycerides were 1.6-1.9 times more active substrates than in mitochondria, whereas CDP-diglycerides from egg lecithin were almost equally active. In contrast to lung mitochondria no cardiolipin synthesis was detected in microsomes. The highest specific activities for phosphatidate cytidyltransferase, CDP-diglyceride-inositol phosphatidyltransferase, choline phosphotransferase, and phosphatidylethanolamine methyltransferase were all found in microsomes. The present in vitro studies and additional evidence (M. Hallman and L. Gluck, (1975) Fed. Proc. 34, 274) support the hypothesis that de novo synthesis of surfactant lecithin phosphatidylinositol and phosphatidylglycerol takes place in the endoplasmic reticulum of alveolar cells.", "contents": "Phosphatidylglycerol in lung surfactant. II. Subcellular distribution and mechanism of biosynthesis in vitro. Lamellar inclusion bodies, apparent precursors for alveolar surfactant lining, have remarkably similar phospholipid composition to surfactant from alveolar lavage, but distinctly different from other fractions studied: mitochondria, microsomal fraction containing endoplasmic reticulum membranes, plasma membranes and nuclei. Surfactant contained (as % of total phospholipid phosphate): 75.5-77.0% lecithin, 11.0-11.2% phosphatidylglycerol, 4.2-4.6% phosphatidylethanolamine, 3.0-3.2% phosphatidylinositol, 1.5-1.7% bis-(monoacylglycerol) phosphate, 1.2-1.9% phosphatidylserine, and 0.7-1.5% sphingomyelin. Fatty acids of phosphatidylglycerol from lamellar bodies were similar to those from microsomes but different from those in mitochondria. Lung homogenate in continuous sucrose density gradient displayed two major activity peaks of phosphatidylglycerol synthesis: the heavier from mitochondria; the lighter from endoplasmic reticulum. Studies on mechanism of phosphatidylglycerol synthesis in vitro revealed (in these two fractions) CDP-diglyceride and sn-glycerol phosphate precursors to phosphatidylglycerol phosphate, that hydrolysed to phosphatidylglycerol. In microsomes disaturated CDP-diglycerides were 1.6-1.9 times more active substrates than in mitochondria, whereas CDP-diglycerides from egg lecithin were almost equally active. In contrast to lung mitochondria no cardiolipin synthesis was detected in microsomes. The highest specific activities for phosphatidate cytidyltransferase, CDP-diglyceride-inositol phosphatidyltransferase, choline phosphotransferase, and phosphatidylethanolamine methyltransferase were all found in microsomes. The present in vitro studies and additional evidence (M. Hallman and L. Gluck, (1975) Fed. Proc. 34, 274) support the hypothesis that de novo synthesis of surfactant lecithin phosphatidylinositol and phosphatidylglycerol takes place in the endoplasmic reticulum of alveolar cells."} {"id": "PMID:172135", "title": "Differential effects of denaturing agents on acetylcholinesterase: insensitivity of the reaction of methanesulfonyl fluoride compared to diisopropylphosphorofluoridate and p-nitrophenyl acetate.", "content": "The effects of various agents that could be expected to perturb enzyme structure in a non-specific and reversible manner (alcohols, dimethylsulfoxide, dimethylformamide, dinitrobenzene, urea and guanidine - HCl) have been determined on reaction of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with a substrate, p-nitrophenyl acetate, and two irreversible inhibitors, diisopropylphosphorofluoridate and methanesulfonyl fluoride. In all three of these reactions an acyl group (acetyl, phosphoryl or sulfonyl respectively) bonds covalently with the active center of the enzyme. As expected, the reactions of p-nitrophenyl acetate and diisopropylphosphorofluoridate were severely retarded by most of these agents. By contrast, reaction of methanesulfonyl fluoride was usually depressed to a far smaller degree, and in two cases was faster. These findings are of interest in connection with: (1) differing requirements for the integrity of tha active center in catalysis with various substrate analogs, and (2) the mechanism by which cationic substrate analogs accelerate reaction of the enzyme with methanesulfonyl fluoride.", "contents": "Differential effects of denaturing agents on acetylcholinesterase: insensitivity of the reaction of methanesulfonyl fluoride compared to diisopropylphosphorofluoridate and p-nitrophenyl acetate. The effects of various agents that could be expected to perturb enzyme structure in a non-specific and reversible manner (alcohols, dimethylsulfoxide, dimethylformamide, dinitrobenzene, urea and guanidine - HCl) have been determined on reaction of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with a substrate, p-nitrophenyl acetate, and two irreversible inhibitors, diisopropylphosphorofluoridate and methanesulfonyl fluoride. In all three of these reactions an acyl group (acetyl, phosphoryl or sulfonyl respectively) bonds covalently with the active center of the enzyme. As expected, the reactions of p-nitrophenyl acetate and diisopropylphosphorofluoridate were severely retarded by most of these agents. By contrast, reaction of methanesulfonyl fluoride was usually depressed to a far smaller degree, and in two cases was faster. These findings are of interest in connection with: (1) differing requirements for the integrity of tha active center in catalysis with various substrate analogs, and (2) the mechanism by which cationic substrate analogs accelerate reaction of the enzyme with methanesulfonyl fluoride."} {"id": "PMID:172136", "title": "Cyclic guanosine 3'-5'-monphosphate. High levels in the male accessory gland of Acheta domesticus and related crickets.", "content": "Guanosine 3',5'-monophosphate (cyclic GMP) was found in the accessory gland of reproductively mature male house crickets (Acheta domesticus (L.)) up to the exceptionally high level of 500 pmol/mg protein (10(-4) mol/kg wet weight). The identity of cricket cyclic GMP was confirmed by enzymatic and spectral analysis. A survey of 10 closely related species of Orthoptera indicated that high levels of cyclic GMP in the accessory gland occur in the subfamily Gryllinae, to which A. domesticus belongs. In these crickets, cyclic GMP in the accessory gland increases together with protein content during two weeks after the final molt. Levels are not augmented by dissection, and are independent of the presence of sperm in the seminal vesicles and of the production of spermatophores by the gland. The function of cyclic GMP in the accessory gland is not yet understood.", "contents": "Cyclic guanosine 3'-5'-monphosphate. High levels in the male accessory gland of Acheta domesticus and related crickets. Guanosine 3',5'-monophosphate (cyclic GMP) was found in the accessory gland of reproductively mature male house crickets (Acheta domesticus (L.)) up to the exceptionally high level of 500 pmol/mg protein (10(-4) mol/kg wet weight). The identity of cricket cyclic GMP was confirmed by enzymatic and spectral analysis. A survey of 10 closely related species of Orthoptera indicated that high levels of cyclic GMP in the accessory gland occur in the subfamily Gryllinae, to which A. domesticus belongs. In these crickets, cyclic GMP in the accessory gland increases together with protein content during two weeks after the final molt. Levels are not augmented by dissection, and are independent of the presence of sperm in the seminal vesicles and of the production of spermatophores by the gland. The function of cyclic GMP in the accessory gland is not yet understood."} {"id": "PMID:172137", "title": "Ascorbate increases the synthesis of procollagen hydroxyproline by cultured fibroblasts from chick embryo tendons without activation of prolyl hydroxyla.", "content": "An improved procedure was developed to extract prolyl hydroxylase from tendon cells of chick embryos with detergent, and improved assays were developed for both the activity of the enzyme and the amount of enzyme protein. Freshly isolated tendon cells were found to contain approx. 100 mug of enzyme protein per 10(8) cells and 40-50% of the enzyme protein was active. When the cells were cultured, they were found to contain the same amount of enzyme protein but only 15-20% of the enzyme protein was active. Gel filtration of cell extracts indicated that the active form of prolyl hydroxylase in freshly isolated tendon cells and incultured tendon cells had the same apparent size and the same activity per mug of immunoreactive protein as enzyme which was shown to be a tetramer. The inactive form was found to have about the same apparent size as subunits of the enzyme. When freshly isolated cells were incubated for 2 h in the presence of 40 mug per ml of ascorbate, there was a slight increase in the rate of hydroxyproline synthesis. In cultured cells, ascorbate at a concentration of 40 mug per ml caused a 2-fold increase in the rate of hydroxyproline synthesis within 30 min. However, ascorbate did not icrease the activity of prolyl hydroxylase in extracts from either cell system. Therefore it appears that the influence of ascorbate on synthesis of procollagen hydroxyproline by the cells studied here must be ascribed to a cofactor effect on the hydroxylation reaction similar to that observed with purified enzyme, and it does not involve \"activation\" of inactive enzyme protein to active enzyme as has been observed in cultures of L-929 and 3T6 mouse fibroblasts.", "contents": "Ascorbate increases the synthesis of procollagen hydroxyproline by cultured fibroblasts from chick embryo tendons without activation of prolyl hydroxyla. An improved procedure was developed to extract prolyl hydroxylase from tendon cells of chick embryos with detergent, and improved assays were developed for both the activity of the enzyme and the amount of enzyme protein. Freshly isolated tendon cells were found to contain approx. 100 mug of enzyme protein per 10(8) cells and 40-50% of the enzyme protein was active. When the cells were cultured, they were found to contain the same amount of enzyme protein but only 15-20% of the enzyme protein was active. Gel filtration of cell extracts indicated that the active form of prolyl hydroxylase in freshly isolated tendon cells and incultured tendon cells had the same apparent size and the same activity per mug of immunoreactive protein as enzyme which was shown to be a tetramer. The inactive form was found to have about the same apparent size as subunits of the enzyme. When freshly isolated cells were incubated for 2 h in the presence of 40 mug per ml of ascorbate, there was a slight increase in the rate of hydroxyproline synthesis. In cultured cells, ascorbate at a concentration of 40 mug per ml caused a 2-fold increase in the rate of hydroxyproline synthesis within 30 min. However, ascorbate did not icrease the activity of prolyl hydroxylase in extracts from either cell system. Therefore it appears that the influence of ascorbate on synthesis of procollagen hydroxyproline by the cells studied here must be ascribed to a cofactor effect on the hydroxylation reaction similar to that observed with purified enzyme, and it does not involve \"activation\" of inactive enzyme protein to active enzyme as has been observed in cultures of L-929 and 3T6 mouse fibroblasts."} {"id": "PMID:172138", "title": "Dependence of gonadotropin-induced steroidogenesis upon RNA and protein synthesis in the interstitial cells of the rat testis.", "content": "The effects of inhibitors of RNA and protein synthesis upon gonadotropic stimulation of testosterone and cyclic AMP production by the Leydig cellwere investigated in vitro with enzyme-dispersed interstitial cells of the rat testis. The testosterone response to human chorionic gonadotropin was abolished by cycloheximide and puromycin, and was markedly reduced by actinomycin D and cordycepin. During 3-h time studies, cycloheximide caused complete inhibition of subsequent steroid production when added at times up to 90 min after the commencement of incubation with human chorionic gonadotropin. Actinomycin D did not completely abolish the testosterone response when added at zero time, and became progressively less effective when added at later times during the incubation period. The stimulation of steroidogenesis by dibutyryl cyclic AMP was also completely abolished by cycloheximide and puromycin, and was significantly reduced by acinomycin D and cordycepin. By contrast with the marked inhibition of steroid production by cycloheximide and actinomycin D, the formation of cyclic AMP during human chorionic gonadotropin stimulation was relatively unaffected by either inhibitor. These results indicate that the stimulation of testosterone production by the Leydig cell in response to gonadotropins and dibutyryl cyclic AMP is dependent upon the synthesis of new RNA and protein moleucles. Thus, effects of gonadotropin and cyclic AMP upon both transcriptional and translational processes appear to be essential intermediate steps in the activation of testicular steroidogenesis. The rapid and complete abolition of subsequent steroid synthesis following addition of cycloheximide or puromycin to human chorionic gonadotropin-stimulated interstitial cells suggests that a relatively labile protein is formed during gonadotropin action.", "contents": "Dependence of gonadotropin-induced steroidogenesis upon RNA and protein synthesis in the interstitial cells of the rat testis. The effects of inhibitors of RNA and protein synthesis upon gonadotropic stimulation of testosterone and cyclic AMP production by the Leydig cellwere investigated in vitro with enzyme-dispersed interstitial cells of the rat testis. The testosterone response to human chorionic gonadotropin was abolished by cycloheximide and puromycin, and was markedly reduced by actinomycin D and cordycepin. During 3-h time studies, cycloheximide caused complete inhibition of subsequent steroid production when added at times up to 90 min after the commencement of incubation with human chorionic gonadotropin. Actinomycin D did not completely abolish the testosterone response when added at zero time, and became progressively less effective when added at later times during the incubation period. The stimulation of steroidogenesis by dibutyryl cyclic AMP was also completely abolished by cycloheximide and puromycin, and was significantly reduced by acinomycin D and cordycepin. By contrast with the marked inhibition of steroid production by cycloheximide and actinomycin D, the formation of cyclic AMP during human chorionic gonadotropin stimulation was relatively unaffected by either inhibitor. These results indicate that the stimulation of testosterone production by the Leydig cell in response to gonadotropins and dibutyryl cyclic AMP is dependent upon the synthesis of new RNA and protein moleucles. Thus, effects of gonadotropin and cyclic AMP upon both transcriptional and translational processes appear to be essential intermediate steps in the activation of testicular steroidogenesis. The rapid and complete abolition of subsequent steroid synthesis following addition of cycloheximide or puromycin to human chorionic gonadotropin-stimulated interstitial cells suggests that a relatively labile protein is formed during gonadotropin action."} {"id": "PMID:172139", "title": "Amylase secretion by rabbit parotid gland. Role of cyclic AMP and cyclic GMP.", "content": "Amylase secretion and changes in the levels of cyclic AMP and GMP were studied in rabbit parotid gland slices incubated in vitro with a variety of neurohumoral transmitters, their analogs and inhibitors. Cyclic GMP levels increased 8-fold 5 min after exposure to carbachol (10(-4) M), without a change in cyclic AMP levels; amylase output also rose. These effects were completely inhibited by muscarinic blockade with atropine, but were unaffected by alpha-adrenergic blockade with phenoxybenzamine. Epinephrine (4 - 10(-5) M) produced a rapid increase in the levels of both cyclic nucleotides and in amylase release. The increase in cyclic GMP level was inhibited by previous exposure of the slices to phenoxybenzamine, while the cyclic AMP rise was prevented by the beta-blocking agent, propranolol. Pure alpha-adrenergic stimulation with methoxamine (4 - 10(-4) M) produced modest elevations in cyclic GMP content and amylase output, effects blocked by pre-treatment of slices with either atropine or phenoxybenzamine. At a concentration of 4 - 10(-6) M, isoproterenol (a beta-agonist) failed to affect cyclic GMP levels, but promptly stimulated increases in cyclic AMP levels, and after a short lag, amylase secretion. At a higher dose (4 - 10(-5) M) isoproterenol produced elevations in the levels of both nucleotides. The carbachol-induced effects on cyclic GMP content and amylase release were greatly potentiated by the addition of isoproterenol (4 - 10(-6) M). These data strongly suggest that cholinergic muscarinic agonists and alpha-adrenergic agonists stimulate amylase output in rabit parotid gland by mechanisms involving cyclic GMP. The atropine-sensitive intracellular events effected by alpha-stimulation may be dependent upon endogenous generation of acetylcholine. Both cyclic nucleotides seem to be required for the early rapid secretion of amylase. The unique responses achieved by the combination of carbachol and isoproterenol suggest that isoproterenol may increase the sensitivity of this tissue to the effects of cholinergic stimuli.", "contents": "Amylase secretion by rabbit parotid gland. Role of cyclic AMP and cyclic GMP. Amylase secretion and changes in the levels of cyclic AMP and GMP were studied in rabbit parotid gland slices incubated in vitro with a variety of neurohumoral transmitters, their analogs and inhibitors. Cyclic GMP levels increased 8-fold 5 min after exposure to carbachol (10(-4) M), without a change in cyclic AMP levels; amylase output also rose. These effects were completely inhibited by muscarinic blockade with atropine, but were unaffected by alpha-adrenergic blockade with phenoxybenzamine. Epinephrine (4 - 10(-5) M) produced a rapid increase in the levels of both cyclic nucleotides and in amylase release. The increase in cyclic GMP level was inhibited by previous exposure of the slices to phenoxybenzamine, while the cyclic AMP rise was prevented by the beta-blocking agent, propranolol. Pure alpha-adrenergic stimulation with methoxamine (4 - 10(-4) M) produced modest elevations in cyclic GMP content and amylase output, effects blocked by pre-treatment of slices with either atropine or phenoxybenzamine. At a concentration of 4 - 10(-6) M, isoproterenol (a beta-agonist) failed to affect cyclic GMP levels, but promptly stimulated increases in cyclic AMP levels, and after a short lag, amylase secretion. At a higher dose (4 - 10(-5) M) isoproterenol produced elevations in the levels of both nucleotides. The carbachol-induced effects on cyclic GMP content and amylase release were greatly potentiated by the addition of isoproterenol (4 - 10(-6) M). These data strongly suggest that cholinergic muscarinic agonists and alpha-adrenergic agonists stimulate amylase output in rabit parotid gland by mechanisms involving cyclic GMP. The atropine-sensitive intracellular events effected by alpha-stimulation may be dependent upon endogenous generation of acetylcholine. Both cyclic nucleotides seem to be required for the early rapid secretion of amylase. The unique responses achieved by the combination of carbachol and isoproterenol suggest that isoproterenol may increase the sensitivity of this tissue to the effects of cholinergic stimuli."} {"id": "PMID:172140", "title": "Collagenolytic activity of carrageenin granuloma in rats.", "content": "Collagenolytic activity at various phases of the development of carrageenin granuloma was investigated by measuring the amount of dialysable hydroxyproline formed during incubation in vitro of minced granulation tissue. Collagenolytic activity reached a maximum at day 8 after carrageenin injection and then decreased gradually, while collagen synthetic activity was rapidly decreased from day 4 to day 11. The significance of dialysable hydroxyproline in native collagen breakdown of carrageenin granuloma is discussed.", "contents": "Collagenolytic activity of carrageenin granuloma in rats. Collagenolytic activity at various phases of the development of carrageenin granuloma was investigated by measuring the amount of dialysable hydroxyproline formed during incubation in vitro of minced granulation tissue. Collagenolytic activity reached a maximum at day 8 after carrageenin injection and then decreased gradually, while collagen synthetic activity was rapidly decreased from day 4 to day 11. The significance of dialysable hydroxyproline in native collagen breakdown of carrageenin granuloma is discussed."} {"id": "PMID:172141", "title": "Effect of adenine nucleotides and pyrophosphate on the exchange of transferrin-bound carbonate.", "content": "1. ATP, ADP and pyrophosphate accelerate the exchange of carbonate of the transferrin-iron-carbonate ternary complex, while AMP, cyclic AMP and phosphate have no effect. 2. ATP promotes carbonate exchange without removing iron from transferrin, whereas pyrophosphate effectiely attacks both the anion and iron components of the ternary complex. 3. Transferrin readily takes over iron from its ATP or pyrophosphate complex. 4. Neither ATP nor pyrophosphate can substitute for carbonate of the ternary complex. These results fit in well with the concept that ATP may play a direct role in the iron uptake by reticulocytes.", "contents": "Effect of adenine nucleotides and pyrophosphate on the exchange of transferrin-bound carbonate. 1. ATP, ADP and pyrophosphate accelerate the exchange of carbonate of the transferrin-iron-carbonate ternary complex, while AMP, cyclic AMP and phosphate have no effect. 2. ATP promotes carbonate exchange without removing iron from transferrin, whereas pyrophosphate effectiely attacks both the anion and iron components of the ternary complex. 3. Transferrin readily takes over iron from its ATP or pyrophosphate complex. 4. Neither ATP nor pyrophosphate can substitute for carbonate of the ternary complex. These results fit in well with the concept that ATP may play a direct role in the iron uptake by reticulocytes."} {"id": "PMID:172142", "title": "Effect of hydrocortisone and glucagon on glycogen metabolism in the fetal rat liver.", "content": "1. Hydrocortisone increases in vivo incorporation of [14C] glucose into fetal liver glycogen in the last days of gestation, whereas in glucagon-treated fetuses, a slight decrease in the incorporation rate was found. 2. Hydrocortisone increases total synthetase activity as that of synthetase a but was without effect on fetal liver glycogen phosphorylase. 3. Glucagon causes a slight increase in phosphorylase a activity on days 19-21, and was without effect on the activities of synthetase a and total synthetase. 4. Dibutyryl cyclic AMP had no effect on the key enzymes of glycogen metabolism 1 h after injection in utero, whereas after 6 h an increase in phosphorylase a activity was found without any change in synthetase a activity.", "contents": "Effect of hydrocortisone and glucagon on glycogen metabolism in the fetal rat liver. 1. Hydrocortisone increases in vivo incorporation of [14C] glucose into fetal liver glycogen in the last days of gestation, whereas in glucagon-treated fetuses, a slight decrease in the incorporation rate was found. 2. Hydrocortisone increases total synthetase activity as that of synthetase a but was without effect on fetal liver glycogen phosphorylase. 3. Glucagon causes a slight increase in phosphorylase a activity on days 19-21, and was without effect on the activities of synthetase a and total synthetase. 4. Dibutyryl cyclic AMP had no effect on the key enzymes of glycogen metabolism 1 h after injection in utero, whereas after 6 h an increase in phosphorylase a activity was found without any change in synthetase a activity."} {"id": "PMID:172143", "title": "A comparison of the structure of hamster pancreatic insulin and insulin extracted from a transplantable hamster islet-cell carcinoma.", "content": "Insulin has been isolated from pancreases of the Syrian hamster and from a transplantable islet-cell tumor of the hamster. Acid/ethanol extraction, ether precipitation, ion exchange and gel filtration chromatography gave preparations of suitable purity for structural studies. Using trypsin cleavage, automatic Edman degradation and manual Edman degradation, a complete sequence of the pancreatic insulin B chain was determined. By automatic Edman degradation, the amino-terminal 10 residues of the pancreatic A chain were assigned and the sequence of carboxy-terminal eleven residues could be deduced by homology to other mammalian and avian insulins. The sequence assigned to hamster insulin A chain is identical to that of the rat, mouse and spiny mouse. The sequence of hamster insulin B chain is identical to rabbit and spiny mouse B chain. In terms of protein evolution, hamster insulin thus appears to occupy an intermediate position between rabbit and rat insulins. Amino acid composition, tryptic peptide composition and partial sequence analysis of the hamster tumor insulin showed no differences from hamster pancreatic insulin.", "contents": "A comparison of the structure of hamster pancreatic insulin and insulin extracted from a transplantable hamster islet-cell carcinoma. Insulin has been isolated from pancreases of the Syrian hamster and from a transplantable islet-cell tumor of the hamster. Acid/ethanol extraction, ether precipitation, ion exchange and gel filtration chromatography gave preparations of suitable purity for structural studies. Using trypsin cleavage, automatic Edman degradation and manual Edman degradation, a complete sequence of the pancreatic insulin B chain was determined. By automatic Edman degradation, the amino-terminal 10 residues of the pancreatic A chain were assigned and the sequence of carboxy-terminal eleven residues could be deduced by homology to other mammalian and avian insulins. The sequence assigned to hamster insulin A chain is identical to that of the rat, mouse and spiny mouse. The sequence of hamster insulin B chain is identical to rabbit and spiny mouse B chain. In terms of protein evolution, hamster insulin thus appears to occupy an intermediate position between rabbit and rat insulins. Amino acid composition, tryptic peptide composition and partial sequence analysis of the hamster tumor insulin showed no differences from hamster pancreatic insulin."} {"id": "PMID:172144", "title": "Proton magnetic resonance studies of peroxidases from turnip and horseradish.", "content": "Proton NMR spectra at 270 MHz have been measured for horseradish peroxidase and turnip peroxidase isoenzymes (P1, P2, P3 and P7) in both their high spin ferric native states and as the low spin ferric cyanide complexes. Resonances of amino acids near the heme have been identified and used to investigate variations in the structure of the heme crevice amongst the enzymes. Ligand proton resonances have been resolved in spectra of the cyanide complexes of the peroxidases and these provide information on the heme electronic structure. The electronic structure of the heme and the tertiary structure of the heme crevice are essentially the same in the acidic turnip isoenzymes, P1, P2 and, to a lesser extent, P3 but differ in the basic turnip enzyme, P7. The heme electronic structure and nature of the iron ligands in peroxidases are discussed. Further evidence is presented for histidine as the proximal ligand. A heme-linked ionizable group with a pK of 6.5 has been detected by NMR in the cyanide complex of horseradish peroxidase.", "contents": "Proton magnetic resonance studies of peroxidases from turnip and horseradish. Proton NMR spectra at 270 MHz have been measured for horseradish peroxidase and turnip peroxidase isoenzymes (P1, P2, P3 and P7) in both their high spin ferric native states and as the low spin ferric cyanide complexes. Resonances of amino acids near the heme have been identified and used to investigate variations in the structure of the heme crevice amongst the enzymes. Ligand proton resonances have been resolved in spectra of the cyanide complexes of the peroxidases and these provide information on the heme electronic structure. The electronic structure of the heme and the tertiary structure of the heme crevice are essentially the same in the acidic turnip isoenzymes, P1, P2 and, to a lesser extent, P3 but differ in the basic turnip enzyme, P7. The heme electronic structure and nature of the iron ligands in peroxidases are discussed. Further evidence is presented for histidine as the proximal ligand. A heme-linked ionizable group with a pK of 6.5 has been detected by NMR in the cyanide complex of horseradish peroxidase."} {"id": "PMID:172145", "title": "Size and charge heterogeneity of rat tissue ferritins.", "content": "Ferritins purified from horse spleen and from rat liver, kidney, heart and hepatoma were analyzed by quantitative polyacrylamide gel electrophoresis. From the migration characteristics of these ferritins at several gel concentrations, Ferguson plots were constructed and the molecular sizes and charges (apparent valences) together with their statistical variability were obtained by applying Rodbard computer programs to the data. Finally, ellipses were drawn describing the 95% confidence limits of these data for size and charge and were used to identify those ferritins that differed in size and/or charge. By these criteria, many of the tissue ferritins were differentiated from one another in terms of their molecular size and/or charge. Among the various tissue ferritin monomers, the molecular sizes were essentially similar (420 000-490 000) except for the two heart ferritins which were larger (530 000 and 626 000, respectively). However, the estimated charges on rat liver, kidney and hepatoma monomers (30-38 net protons per molecule) differed from that of spleen monomer (51 net protons per molecule) while the larger rat heart ferritin also had a greater charge (83 net protons) than the smaller (40 net protons). Apoferritins prepared chemically by removal of iron from the holoferritins had migration properties indistinguishable from the parent holoferritins. The migration properties of minor (dimeric) ferritin bands on the gels were compared with those of the monomer bands. The molecular sizes of the minor bands were larger than those of the major bands, and were not inconsistent with a doubling in size. However, charge differences varied, being either similar for major and minor forms (spleen ferritin), approximately twice for the minor form (rat hepatoma ferritin) or five times greater for the minor form (rat liver ferritin). These differences in behavior were confirmed by using minimally sieving gels, on which the major bands of horse spleen ferritin failed to separate whereas those of rat liver ferritin were readily separable. It is concluded that dimers of ferritins from different tissues may associate in different ways.", "contents": "Size and charge heterogeneity of rat tissue ferritins. Ferritins purified from horse spleen and from rat liver, kidney, heart and hepatoma were analyzed by quantitative polyacrylamide gel electrophoresis. From the migration characteristics of these ferritins at several gel concentrations, Ferguson plots were constructed and the molecular sizes and charges (apparent valences) together with their statistical variability were obtained by applying Rodbard computer programs to the data. Finally, ellipses were drawn describing the 95% confidence limits of these data for size and charge and were used to identify those ferritins that differed in size and/or charge. By these criteria, many of the tissue ferritins were differentiated from one another in terms of their molecular size and/or charge. Among the various tissue ferritin monomers, the molecular sizes were essentially similar (420 000-490 000) except for the two heart ferritins which were larger (530 000 and 626 000, respectively). However, the estimated charges on rat liver, kidney and hepatoma monomers (30-38 net protons per molecule) differed from that of spleen monomer (51 net protons per molecule) while the larger rat heart ferritin also had a greater charge (83 net protons) than the smaller (40 net protons). Apoferritins prepared chemically by removal of iron from the holoferritins had migration properties indistinguishable from the parent holoferritins. The migration properties of minor (dimeric) ferritin bands on the gels were compared with those of the monomer bands. The molecular sizes of the minor bands were larger than those of the major bands, and were not inconsistent with a doubling in size. However, charge differences varied, being either similar for major and minor forms (spleen ferritin), approximately twice for the minor form (rat hepatoma ferritin) or five times greater for the minor form (rat liver ferritin). These differences in behavior were confirmed by using minimally sieving gels, on which the major bands of horse spleen ferritin failed to separate whereas those of rat liver ferritin were readily separable. It is concluded that dimers of ferritins from different tissues may associate in different ways."} {"id": "PMID:172146", "title": "Studies on epsilon-prototoxin of Clostridium perfringens type D. Physicochemical and chemical properties of epsilon-prototoxin.", "content": "epsilon-Prototoxin of clostridium perfringens type D consists of one polypeptide chain of 311 amino acids with the following composition: Asp52 Thr31 Ser25 Glu28 Pro12 Gly17 Ala14 Val28 Met5 Ile15 Leu18 Tyr17 Phe8 Lys31 His2 Arg5 Tyr2. It has no free cysteine but contains one blocked cysteine. The N-terminal as well as the C-terminal residue is lysine. The ultracentrifuge pattern gave one single boundary having S020,w = 2.15 S and Do20,w = 5.56-10(-7) cm2/s. Calculation of the molecular weight from D020,w and S020,w gave a value of 34 250. The molecular weight determined from sedimentation equilibrium using ultraviolet optics gave a value of 33 000 +/- 1000. On the other hand molecular weights calculated from a calibrated Sephadex G-100 column in borate buffer was 25 000 and that in sodium phosphate, ionic strength 0.2, was 27 500. This discrepancy between values obtained in the ultracentrifuge and by gel filtration is attributed to adsorption of epsilon-prototoxin by Sephadex.", "contents": "Studies on epsilon-prototoxin of Clostridium perfringens type D. Physicochemical and chemical properties of epsilon-prototoxin. epsilon-Prototoxin of clostridium perfringens type D consists of one polypeptide chain of 311 amino acids with the following composition: Asp52 Thr31 Ser25 Glu28 Pro12 Gly17 Ala14 Val28 Met5 Ile15 Leu18 Tyr17 Phe8 Lys31 His2 Arg5 Tyr2. It has no free cysteine but contains one blocked cysteine. The N-terminal as well as the C-terminal residue is lysine. The ultracentrifuge pattern gave one single boundary having S020,w = 2.15 S and Do20,w = 5.56-10(-7) cm2/s. Calculation of the molecular weight from D020,w and S020,w gave a value of 34 250. The molecular weight determined from sedimentation equilibrium using ultraviolet optics gave a value of 33 000 +/- 1000. On the other hand molecular weights calculated from a calibrated Sephadex G-100 column in borate buffer was 25 000 and that in sodium phosphate, ionic strength 0.2, was 27 500. This discrepancy between values obtained in the ultracentrifuge and by gel filtration is attributed to adsorption of epsilon-prototoxin by Sephadex."} {"id": "PMID:172147", "title": "Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver and hepatomas AH-130, 3924A and 5123.", "content": "The cholesterol to phospholipid ratio in mitochondria from hepatomas AH-130, 3924A and 5123 is higher than in the particles isolated from adult or fetal rat livers. Nearly all the cholesterol of hepatoma mitochondria is located in membranes. As in liver mitochondria, in the particles isolated from hepatoma AH-130 there is more cholesterol in the outer than in the inner membrane. In mitochondria from cholesterol-enriched liver and hepatomas, there occurs a decrease in extent of hypoosmotic and phosphate-induced swelling and a decrease of conformational changes linked to energy states. The phenomenon is more marked in particles which exhibit higher cholesterol to phospholipid ratios. A statistically significant negative correlation exists between the cholesterol to phospholipid ratio and extent of volume or conformational changes. No significant modifications of these parameters were found in fetal liver mitochondria. Cholesterol content does not influence K+ uptake by cholesterol-enriched or hepatoma mitochondria. Nor does cholesterol content affect the respiratory increment related to this uptake. As a consequence of K+ uptake, total mitochondrial water exchangeable with tritiated water rises 20% while sucrose-impermeable water rises 42-48% in both adult rat liver and hepatoma AH-130 mitochondria. Absorbance changes linked to ion uptake do not correspond merely to variations in mitochondrial water content. Water content is apparently not influenced by the cholesterol to phospholipid ratio. However, the ratio is significantly correlated to both extent and initial rate of absorbance decrease of mitochondrial suspensions during K+ uptake. The higher the ratio, the lower the extent and initial rate of absorbance decrease.", "contents": "Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver and hepatomas AH-130, 3924A and 5123. The cholesterol to phospholipid ratio in mitochondria from hepatomas AH-130, 3924A and 5123 is higher than in the particles isolated from adult or fetal rat livers. Nearly all the cholesterol of hepatoma mitochondria is located in membranes. As in liver mitochondria, in the particles isolated from hepatoma AH-130 there is more cholesterol in the outer than in the inner membrane. In mitochondria from cholesterol-enriched liver and hepatomas, there occurs a decrease in extent of hypoosmotic and phosphate-induced swelling and a decrease of conformational changes linked to energy states. The phenomenon is more marked in particles which exhibit higher cholesterol to phospholipid ratios. A statistically significant negative correlation exists between the cholesterol to phospholipid ratio and extent of volume or conformational changes. No significant modifications of these parameters were found in fetal liver mitochondria. Cholesterol content does not influence K+ uptake by cholesterol-enriched or hepatoma mitochondria. Nor does cholesterol content affect the respiratory increment related to this uptake. As a consequence of K+ uptake, total mitochondrial water exchangeable with tritiated water rises 20% while sucrose-impermeable water rises 42-48% in both adult rat liver and hepatoma AH-130 mitochondria. Absorbance changes linked to ion uptake do not correspond merely to variations in mitochondrial water content. Water content is apparently not influenced by the cholesterol to phospholipid ratio. However, the ratio is significantly correlated to both extent and initial rate of absorbance decrease of mitochondrial suspensions during K+ uptake. The higher the ratio, the lower the extent and initial rate of absorbance decrease."} {"id": "PMID:172148", "title": "Subfractionation of rat liver plasma membrane. Uneven distribution of plasma membrane-bound enzymes on the liver cell surface.", "content": "Plasma membranes were isolated from rat liver mainly under isotonic conditions. As marker enzymes for the plasma membrane, 5'-nucleotidase and (Na+ + K+)-ATPase were used. The yield of plasma membrane was 0.6-0.9 mg protein per g wet weight of liver. The recovery of 5'-nucleotidase and (Na+ +K+)-ATPase activity was 18 and 48% of the total activity of the whole-liver homogenate, respectively. Judged from the activity of glucose-6-phosphatase and succinate dehydrogenase in the plasma membrane, and from the electron microscopic observation of it, the contamination by microsomes and mitochondria was very low. A further homogenization of the plasma membrane yielded two fractions, the light and heavy fractions, in a discontinuous sucrose gradient centrifugation. The light fraction showed higher specific activities of 5'-nucleotidase, alkaline phosphatase, (Na+ +K+)-ATPase and Mg2+-ATPase, whereas the heavy one showed a higher specific activity of adenylate cyclase. Ligation of the bile duct for 48 h decreased the specific activities of (Na2+ +K+)-ATPase and Mg2+-ATPase in the light fraction, whereas it had no significant influence on the activities of these enzymes in the heavy fraction. The specific activity of alkaline phosphate was elevated in both fractions by the obstruction of the bile flow. Electron microscopy on sections of the plasma membrane subfractions showed that the light fraction consisted of vesicles of various sizes and that the heavy fractions contained membrane sheets and paired membrane strips connected by junctional complexes, as well as vesicles. The origin of these two fractions is discussed and it is suggested that the light fraction was derived from the bile front of the liver cell surface and the heavy one contained the blood front and the lateral surface of it.", "contents": "Subfractionation of rat liver plasma membrane. Uneven distribution of plasma membrane-bound enzymes on the liver cell surface. Plasma membranes were isolated from rat liver mainly under isotonic conditions. As marker enzymes for the plasma membrane, 5'-nucleotidase and (Na+ + K+)-ATPase were used. The yield of plasma membrane was 0.6-0.9 mg protein per g wet weight of liver. The recovery of 5'-nucleotidase and (Na+ +K+)-ATPase activity was 18 and 48% of the total activity of the whole-liver homogenate, respectively. Judged from the activity of glucose-6-phosphatase and succinate dehydrogenase in the plasma membrane, and from the electron microscopic observation of it, the contamination by microsomes and mitochondria was very low. A further homogenization of the plasma membrane yielded two fractions, the light and heavy fractions, in a discontinuous sucrose gradient centrifugation. The light fraction showed higher specific activities of 5'-nucleotidase, alkaline phosphatase, (Na+ +K+)-ATPase and Mg2+-ATPase, whereas the heavy one showed a higher specific activity of adenylate cyclase. Ligation of the bile duct for 48 h decreased the specific activities of (Na2+ +K+)-ATPase and Mg2+-ATPase in the light fraction, whereas it had no significant influence on the activities of these enzymes in the heavy fraction. The specific activity of alkaline phosphate was elevated in both fractions by the obstruction of the bile flow. Electron microscopy on sections of the plasma membrane subfractions showed that the light fraction consisted of vesicles of various sizes and that the heavy fractions contained membrane sheets and paired membrane strips connected by junctional complexes, as well as vesicles. The origin of these two fractions is discussed and it is suggested that the light fraction was derived from the bile front of the liver cell surface and the heavy one contained the blood front and the lateral surface of it."} {"id": "PMID:172149", "title": "Comparison of the secretory processes in the parotid and sublingual glands of the mouse. 1. Regulation of the secretory processes.", "content": "1. Secretion from the mucous sublingual gland of the mouse has been investigated and compared with the serous parotid gland. The influence of acetylcholine, noradrenalin and adrenalin on the secretion of glycoproteins (e.g. mucins) and proteins (e.g. amylase) from these glands in vitro, and the involvement of cyclic AMP and Ca2+ has been studied. 2. Secretion from the parotid gland could be stimulated by both acetylcholine and the catecholamines. It appears that cyclic AMP plays an important role in the adrenergic secretory process, but not in the cholinergic-induced secretion. In the latter case, exogenous Ca2+ strongly increased the secretion. 3. Mucin secretion from the sublingual gland could be affected by acetylcholine in the presence of exogenous Ca2+. Noradrenalin and adrenalin induced only a slow mucin secretion and, for this secretory process, exogenous Ca2+ is also required. Though cyclic AMP is present in the sublingual gland, no influence on its level could be detected in this gland after stimulation of the adrenergic beta-receptor, whereas, in contrast to the parotid gland, dibutyryl cyclic AMP induced only a slow secretion. Because it was observed that the sublingual gland of the mouse is not innervated sympathetically, it seems reasonable to suppose that the catecholamines stimulate the mucin secretion from this gland via hormonal receptors and not via the adrenergic beta-receptor. 4. The protein secretion from the sublingual gland could be stimulated by both acetylcholine and the catecholamines. An involvement of cyclic AMP in this process was not observed. Addition of exogenous Ca2+ is less important, as was found for the mucin secretion. So it has been concluded that protein and mucin secretion from the sublingual gland are regulated via different pathways.", "contents": "Comparison of the secretory processes in the parotid and sublingual glands of the mouse. 1. Regulation of the secretory processes. 1. Secretion from the mucous sublingual gland of the mouse has been investigated and compared with the serous parotid gland. The influence of acetylcholine, noradrenalin and adrenalin on the secretion of glycoproteins (e.g. mucins) and proteins (e.g. amylase) from these glands in vitro, and the involvement of cyclic AMP and Ca2+ has been studied. 2. Secretion from the parotid gland could be stimulated by both acetylcholine and the catecholamines. It appears that cyclic AMP plays an important role in the adrenergic secretory process, but not in the cholinergic-induced secretion. In the latter case, exogenous Ca2+ strongly increased the secretion. 3. Mucin secretion from the sublingual gland could be affected by acetylcholine in the presence of exogenous Ca2+. Noradrenalin and adrenalin induced only a slow mucin secretion and, for this secretory process, exogenous Ca2+ is also required. Though cyclic AMP is present in the sublingual gland, no influence on its level could be detected in this gland after stimulation of the adrenergic beta-receptor, whereas, in contrast to the parotid gland, dibutyryl cyclic AMP induced only a slow secretion. Because it was observed that the sublingual gland of the mouse is not innervated sympathetically, it seems reasonable to suppose that the catecholamines stimulate the mucin secretion from this gland via hormonal receptors and not via the adrenergic beta-receptor. 4. The protein secretion from the sublingual gland could be stimulated by both acetylcholine and the catecholamines. An involvement of cyclic AMP in this process was not observed. Addition of exogenous Ca2+ is less important, as was found for the mucin secretion. So it has been concluded that protein and mucin secretion from the sublingual gland are regulated via different pathways."} {"id": "PMID:172150", "title": "Distribution of ferritin-conjugated lectins on sialidase-treated membranes of human erythrocytes.", "content": "The labeling of sialidase-treated, human erythrocyte membranes with ferritin-conjugates of four plant lectins, concanavalin A, Ricinus communis hemagglutinin, Bauhinia purpurea hemagglutinin and Arachis hypogoea hemagglutinin, is reported. Among these ferritin-conjugated lectins, ferritin-conjugated concanavalin A and ferritin-conjugated R. communis hemagglutinin were found in clusters on the sialidase-treated membranes, whereas ferritin-conjugated B. purpurea hemagglutinin and ferritin-conjugated A. hypogoea hemagglutinin were found in a random distribution on the membranes. Furthermore, when the membranes were labeled with a mixutre of concanavalin A and ferritin-conjugated B. purpurea hemagglutinin, ferritin particles were found in clusters, indicating that the membrane receptors for B. purpurea hemagglutinin were forced to more together with those for concanavalin A. A method for the quantitative estimation of the clustering of ferritin particles on the membranes was also devised and applied to the labeling of sialidase-treated, human erythrocyte membranes with the above four ferritin-conjugated lectins.", "contents": "Distribution of ferritin-conjugated lectins on sialidase-treated membranes of human erythrocytes. The labeling of sialidase-treated, human erythrocyte membranes with ferritin-conjugates of four plant lectins, concanavalin A, Ricinus communis hemagglutinin, Bauhinia purpurea hemagglutinin and Arachis hypogoea hemagglutinin, is reported. Among these ferritin-conjugated lectins, ferritin-conjugated concanavalin A and ferritin-conjugated R. communis hemagglutinin were found in clusters on the sialidase-treated membranes, whereas ferritin-conjugated B. purpurea hemagglutinin and ferritin-conjugated A. hypogoea hemagglutinin were found in a random distribution on the membranes. Furthermore, when the membranes were labeled with a mixutre of concanavalin A and ferritin-conjugated B. purpurea hemagglutinin, ferritin particles were found in clusters, indicating that the membrane receptors for B. purpurea hemagglutinin were forced to more together with those for concanavalin A. A method for the quantitative estimation of the clustering of ferritin particles on the membranes was also devised and applied to the labeling of sialidase-treated, human erythrocyte membranes with the above four ferritin-conjugated lectins."} {"id": "PMID:172151", "title": "Biochemical characteristics of the outer membranes of plant mitochondria.", "content": "Like the outer membranes of liver mitochondria, those of plant mitochondria are impermeable to cytochrome c when intact and can be ruptured by osmotic shock. Isolated plant outer mitochondrial membranes are also similar to the corresponding liver membranes in terms of phospholipid and sterol content. Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis experiments indicate that a single class of proteins (apparent molecular weight 30 000) comprises the bulk of the plant outer membrane protein. There are also considerable amounts of polysaccharide associated with these membranes, which may contribute to their osmotic stability.", "contents": "Biochemical characteristics of the outer membranes of plant mitochondria. Like the outer membranes of liver mitochondria, those of plant mitochondria are impermeable to cytochrome c when intact and can be ruptured by osmotic shock. Isolated plant outer mitochondrial membranes are also similar to the corresponding liver membranes in terms of phospholipid and sterol content. Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis experiments indicate that a single class of proteins (apparent molecular weight 30 000) comprises the bulk of the plant outer membrane protein. There are also considerable amounts of polysaccharide associated with these membranes, which may contribute to their osmotic stability."} {"id": "PMID:172153", "title": "Effect of colchicine on the osmotic water flow across the toad urinary bladder.", "content": "Osmotic water movement across the toad urinary bladder in response to both vasopressin and cyclic AMP was inhibited by 10(-5) to 10(-4) M colchicine on the serosal but not on the mucosal side. This inhibitory effect was found to be time- and dose-dependent. Colchicine alone did not change basal osmotic flow and a baseline of the short-circuit current (Isc) and also did not affect a vasopressin-induced rise of the Isc. The inhibitory effect was not prevented by the addition of pyruvate. The osmotic water movement produced by 360 mM Urea (mucosal), 360 mM mannitol (serosal) or 2 mug/ml amphotericin B (mucosal), was not affected by 10(-4) M colchicine. These results suggest that colchicine inhibits some biological process subsequent to the formation of cyclic AMP except a directional cytoplasmic streaming process where microtubules may be involved.", "contents": "Effect of colchicine on the osmotic water flow across the toad urinary bladder. Osmotic water movement across the toad urinary bladder in response to both vasopressin and cyclic AMP was inhibited by 10(-5) to 10(-4) M colchicine on the serosal but not on the mucosal side. This inhibitory effect was found to be time- and dose-dependent. Colchicine alone did not change basal osmotic flow and a baseline of the short-circuit current (Isc) and also did not affect a vasopressin-induced rise of the Isc. The inhibitory effect was not prevented by the addition of pyruvate. The osmotic water movement produced by 360 mM Urea (mucosal), 360 mM mannitol (serosal) or 2 mug/ml amphotericin B (mucosal), was not affected by 10(-4) M colchicine. These results suggest that colchicine inhibits some biological process subsequent to the formation of cyclic AMP except a directional cytoplasmic streaming process where microtubules may be involved."} {"id": "PMID:172154", "title": "Choleragen stimulates steroidogenesis and adenylate cyclase in cells lacking functional hormone receptors.", "content": "Choleragen stimulates steroid secretion and adenylate cyclase in three cell lines, adrenal tumor line (Y-1), a corticotropin-resistant mutant derived from Y-1 called OS-3, and a receptor-deficient Leydig tumor line (I-10). Sensitivity for half-maximal stimulation varies from 3 to 36 pM choleragen, the I-10 line being the most sensitive. Latency before the onset of steroidogenesis is longer in OS-3 and I-10 cells than in the Y-1 line. In both OS-3 and I-10 cells choleragen stimulates adenylate cyclase whether ITP or 5'-guanylylimidodiphosphate is the regulatory cofactor used. In addition to the responses of the receptor-deficient lines, choleragen does not, during its latency, block the response to corticotropin in Y-1 cells; corticotropin does not block binding of 125I-labeled choleragen to Y-1 cells; gangliosides do not interfere with the corticotropin-induced stimulation of Y-1 cells. We conclude that the corticotropin and choleragen receptors are different.", "contents": "Choleragen stimulates steroidogenesis and adenylate cyclase in cells lacking functional hormone receptors. Choleragen stimulates steroid secretion and adenylate cyclase in three cell lines, adrenal tumor line (Y-1), a corticotropin-resistant mutant derived from Y-1 called OS-3, and a receptor-deficient Leydig tumor line (I-10). Sensitivity for half-maximal stimulation varies from 3 to 36 pM choleragen, the I-10 line being the most sensitive. Latency before the onset of steroidogenesis is longer in OS-3 and I-10 cells than in the Y-1 line. In both OS-3 and I-10 cells choleragen stimulates adenylate cyclase whether ITP or 5'-guanylylimidodiphosphate is the regulatory cofactor used. In addition to the responses of the receptor-deficient lines, choleragen does not, during its latency, block the response to corticotropin in Y-1 cells; corticotropin does not block binding of 125I-labeled choleragen to Y-1 cells; gangliosides do not interfere with the corticotropin-induced stimulation of Y-1 cells. We conclude that the corticotropin and choleragen receptors are different."} {"id": "PMID:172155", "title": "Endotoxic lipopolysaccharides stimulate steroidogenesis and adenylate cyclase in adrenal tumor cells.", "content": "Lipopolysaccharides (endotoxins) from Escherichia coli, Serratia marcesens and Salmonella typhosa stimulated steroid production in Y-1 adrenal tumor cells in culture with a latent period of 3-4 h. Lipid A, derived from Escherichia coli lipopolysaccharide, also stimulated steroidogenesis. Lipopolysaccharides and lipid A also stimulate adenylate cyclase activity and cause rounding of the cells. In contrast, lipopolysaccharides do not stimulate steroidogenesis in receptor-deficient adrenal tumor cells (OS-3) or Leydig tumor cells (I-10). This tends to rule out contamination by enterotoxin to which these lines respond. Although both hormone and lipopolysaccharide responses are lost in these lines, there was no interaction between these sites as judged by the failure of lipopolysaccharides to block, during their latency, the response to corticotropin in Y-1 cells. The possibility that the lipopolysaccharide effect is one on membrane conformation is discussed.", "contents": "Endotoxic lipopolysaccharides stimulate steroidogenesis and adenylate cyclase in adrenal tumor cells. Lipopolysaccharides (endotoxins) from Escherichia coli, Serratia marcesens and Salmonella typhosa stimulated steroid production in Y-1 adrenal tumor cells in culture with a latent period of 3-4 h. Lipid A, derived from Escherichia coli lipopolysaccharide, also stimulated steroidogenesis. Lipopolysaccharides and lipid A also stimulate adenylate cyclase activity and cause rounding of the cells. In contrast, lipopolysaccharides do not stimulate steroidogenesis in receptor-deficient adrenal tumor cells (OS-3) or Leydig tumor cells (I-10). This tends to rule out contamination by enterotoxin to which these lines respond. Although both hormone and lipopolysaccharide responses are lost in these lines, there was no interaction between these sites as judged by the failure of lipopolysaccharides to block, during their latency, the response to corticotropin in Y-1 cells. The possibility that the lipopolysaccharide effect is one on membrane conformation is discussed."} {"id": "PMID:172156", "title": "Changes in lipid metabolism and cell morphology following attack by phospholipase C (Clostridium perfringens) on red cells or lymphocytes.", "content": "When intact human erythrocytes were treated with phospholipase C (Clostridium perfringens), up to 30% of the membrane phospholipids were broken down without significant cell lysis. Only phosphatidylcholine and sphingomyelin were attacked. Ceramide (derived from sphingomyelin) accumulated, but 1,2-diacylglycerol (derived from phosphatidylcholine) was largely converted into phosphatidate. Up to 12% of the cell phospholipid could be converted into phosphatidate in this way. Pig erythrocytes and lymphocytes showed a similar but smaller synthesis of phosphatidate after phospholipase C attack. Phospholipase C also caused a marked morphological change in erythrocytes, giving rise to spherical cells containing internal membrane vesicles. This change appeared to be due to ceramide and de and diacylglycerol accumulation rather than to increased phosphatidate content of the cells.", "contents": "Changes in lipid metabolism and cell morphology following attack by phospholipase C (Clostridium perfringens) on red cells or lymphocytes. When intact human erythrocytes were treated with phospholipase C (Clostridium perfringens), up to 30% of the membrane phospholipids were broken down without significant cell lysis. Only phosphatidylcholine and sphingomyelin were attacked. Ceramide (derived from sphingomyelin) accumulated, but 1,2-diacylglycerol (derived from phosphatidylcholine) was largely converted into phosphatidate. Up to 12% of the cell phospholipid could be converted into phosphatidate in this way. Pig erythrocytes and lymphocytes showed a similar but smaller synthesis of phosphatidate after phospholipase C attack. Phospholipase C also caused a marked morphological change in erythrocytes, giving rise to spherical cells containing internal membrane vesicles. This change appeared to be due to ceramide and de and diacylglycerol accumulation rather than to increased phosphatidate content of the cells."} {"id": "PMID:172157", "title": "A comparison of DNA from free living and endosymbiotic Rhizobium leguminosarum (strain PRE).", "content": "1. Bacteroids of Rhizobium leguminosarum (strain PRE) purified from root nodules of Pisum sativum (var. 'Rondo') by the standard procedure of differential centrifugation contained considerable contamination of mitochondrial material. This could be removed by incubation of the bacteroid preparation with 1 M KCl/1% deoxycholate. 2. The DNA content of bacteroid cells of R. leguminosarum was found to have increased about three fold in comparison with the DNA content of free living R. leguminosarum bacteria. 3. No significant difference in DNA composition of free living R. leguminosarum bacteria and bacteroids could be detected by CsCl equilibrium centrifugation, RNA - DNA hybridization and DNA - DNA reassociation studies.", "contents": "A comparison of DNA from free living and endosymbiotic Rhizobium leguminosarum (strain PRE). 1. Bacteroids of Rhizobium leguminosarum (strain PRE) purified from root nodules of Pisum sativum (var. 'Rondo') by the standard procedure of differential centrifugation contained considerable contamination of mitochondrial material. This could be removed by incubation of the bacteroid preparation with 1 M KCl/1% deoxycholate. 2. The DNA content of bacteroid cells of R. leguminosarum was found to have increased about three fold in comparison with the DNA content of free living R. leguminosarum bacteria. 3. No significant difference in DNA composition of free living R. leguminosarum bacteria and bacteroids could be detected by CsCl equilibrium centrifugation, RNA - DNA hybridization and DNA - DNA reassociation studies."} {"id": "PMID:172159", "title": "[Photoinduced reduction of ferriperoxidase. I. Reaction with reduced nicotinamide-adenine dinucleotide].", "content": "Photoinduced reduction of peroxidase with reduced NAD is revealed.; its kinetics is studied. The kinetic scheme of this process is suggested and calculated. It is shown that metastable excited state appears after NAD-N irradiation. This state participated in the reaction with ferriperosidase. It is also shown that the NAD radical which appears in the course of this reaction reduces the peroxidase; the rate constant of this process is (5 +/- 0,5) -10(4) M-1 sec-1.", "contents": "[Photoinduced reduction of ferriperoxidase. I. Reaction with reduced nicotinamide-adenine dinucleotide]. Photoinduced reduction of peroxidase with reduced NAD is revealed.; its kinetics is studied. The kinetic scheme of this process is suggested and calculated. It is shown that metastable excited state appears after NAD-N irradiation. This state participated in the reaction with ferriperosidase. It is also shown that the NAD radical which appears in the course of this reaction reduces the peroxidase; the rate constant of this process is (5 +/- 0,5) -10(4) M-1 sec-1."} {"id": "PMID:172160", "title": "[Kinetics of dark reduction of P700 centers in photosynthesis].", "content": "Relationship between the rate of dark fall of ESR I signal in the chloroplasts and light intensity 710 nm was studied. It is shown that the kinetics of the signal drop at sufficiently high levels of intensity is a biphase one. The fast phase (2 sec) disappears in the presence of an inhibitor of noncyclic electron transfer. It is concluded that the kinetics of electron transport is not described within the concept of the linear chain of electron carriers and a suggestion is put forward concerning a possible mechanism of this process which depends on the participation of plastoquinone in electron transport.", "contents": "[Kinetics of dark reduction of P700 centers in photosynthesis]. Relationship between the rate of dark fall of ESR I signal in the chloroplasts and light intensity 710 nm was studied. It is shown that the kinetics of the signal drop at sufficiently high levels of intensity is a biphase one. The fast phase (2 sec) disappears in the presence of an inhibitor of noncyclic electron transfer. It is concluded that the kinetics of electron transport is not described within the concept of the linear chain of electron carriers and a suggestion is put forward concerning a possible mechanism of this process which depends on the participation of plastoquinone in electron transport."} {"id": "PMID:172164", "title": "Partial characterization of the 1-anilino-8-naphthalene sulfonate-adrenochrome semicarbazide interaction site in erythrocyte ghost membrane fragments.", "content": "The effect of adrenochrome semicarbazide on the conformation of erythrocyte ghost membranes has been studied by ANS fluorescence, lipid and sulfhydryl spin labels and circular dichroism. No large conformational alterations in the membrane were detected by these techniques. Noncompetitive quenching of ANS fluorescence by ADCS suggests ADCS to interact with the membrane at sites close to the ANS binding domain.", "contents": "Partial characterization of the 1-anilino-8-naphthalene sulfonate-adrenochrome semicarbazide interaction site in erythrocyte ghost membrane fragments. The effect of adrenochrome semicarbazide on the conformation of erythrocyte ghost membranes has been studied by ANS fluorescence, lipid and sulfhydryl spin labels and circular dichroism. No large conformational alterations in the membrane were detected by these techniques. Noncompetitive quenching of ANS fluorescence by ADCS suggests ADCS to interact with the membrane at sites close to the ANS binding domain."} {"id": "PMID:172161", "title": "[Propagation of spikes in statistical neuron ensembles. I. Concept of phase transitions].", "content": "A system of two coupled integro-differential equations for the propagation of sipkes is presented. A qualitative consideration of the system shows possibility of concentrational phase transition in the neuron ensemble from the state of spontaneous firing to the strong periodic oscilltation activity. Naer the point of the phase transition the neuron ensemble becomes labile, which maintains appropriate conditons for the existence of mosaic structures in the neuron network.", "contents": "[Propagation of spikes in statistical neuron ensembles. I. Concept of phase transitions]. A system of two coupled integro-differential equations for the propagation of sipkes is presented. A qualitative consideration of the system shows possibility of concentrational phase transition in the neuron ensemble from the state of spontaneous firing to the strong periodic oscilltation activity. Naer the point of the phase transition the neuron ensemble becomes labile, which maintains appropriate conditons for the existence of mosaic structures in the neuron network."} {"id": "PMID:172167", "title": "[Basis for the use of Pierre's method for the determination of ACTH in human blood plasma].", "content": "Adrenal glands of rats were immersed in Ringer-Lock solution (used as control), other rat adrenal glands were immersed in human blood plasma. The amount of corticosterone in the extracts received was estimated after two hours of incubation. The activity of adrenocorticotropic function of the pituitary gland of the patients examined was judged by the difference in the corticosterone indices in these extracts. ACTH (1.5 and 10 mkg) was added to the plasma to determine the sensitivity of this technique. Regular and significant increase in corticosterone was revealed. Modified Pierre's technique can be applied for ACTH determination in man.", "contents": "[Basis for the use of Pierre's method for the determination of ACTH in human blood plasma]. Adrenal glands of rats were immersed in Ringer-Lock solution (used as control), other rat adrenal glands were immersed in human blood plasma. The amount of corticosterone in the extracts received was estimated after two hours of incubation. The activity of adrenocorticotropic function of the pituitary gland of the patients examined was judged by the difference in the corticosterone indices in these extracts. ACTH (1.5 and 10 mkg) was added to the plasma to determine the sensitivity of this technique. Regular and significant increase in corticosterone was revealed. Modified Pierre's technique can be applied for ACTH determination in man."} {"id": "PMID:172168", "title": "[Interrelationship of the mediator receptors in the terminals of the afferent nerves of the cornea of the eye].", "content": "In local application of substances with a mediator action (adrenaline, acetylcholine, histamine) and blockers of specific receptors (dihydroergotoxin, inderal, atropine and of subcutaneous dimedrol) together with dicaine it was possible to reveal a distinct presence in the cornea of the eye of the mediator receptors capable of influencing one another. Pharmacological analysis permitted a supposition to be made that there were two receptor systems in the sensory nerve endings of the cornea; these systems were in reciprocal inhibitory relations; due to this their regular influence on the processes of excitation and inhibition is effected in the sensory nerve ending.", "contents": "[Interrelationship of the mediator receptors in the terminals of the afferent nerves of the cornea of the eye]. In local application of substances with a mediator action (adrenaline, acetylcholine, histamine) and blockers of specific receptors (dihydroergotoxin, inderal, atropine and of subcutaneous dimedrol) together with dicaine it was possible to reveal a distinct presence in the cornea of the eye of the mediator receptors capable of influencing one another. Pharmacological analysis permitted a supposition to be made that there were two receptor systems in the sensory nerve endings of the cornea; these systems were in reciprocal inhibitory relations; due to this their regular influence on the processes of excitation and inhibition is effected in the sensory nerve ending."} {"id": "PMID:172169", "title": "[Some indices of the activity of the brain in \"rapid\" sleep preceeded or not preceeded by delta-sleep].", "content": "In order to study the functional interaction between the delta sleep and the REM sleep some psychophysiological features of REM sleep were examined in REM-onset (without any preceding delta sleep--\"early REM period\") and in the REM period (REMP) terminating the normal sleep cycle (with the preceding delta sleep) of 92 daytime sleep attacks in 10 narcoleptic patients. Under these conditions the significant differences exist in the characteristics of the dream reports and in subjective estimations of sleep quality and duration. Sleep was evaluated as \"superficial\" and underestimations of sleep duration took place after an early REMP. Correct estimations of sleep duration and evaluations of sleep as \"deep\" dominated after REMP enging sleep cycles. The results obtained indicate the functional interaction between the delta sleep and REM sleep existing in the sleep cycle and largely determining the psychic content of the brain activity in the REM sleep.", "contents": "[Some indices of the activity of the brain in \"rapid\" sleep preceeded or not preceeded by delta-sleep]. In order to study the functional interaction between the delta sleep and the REM sleep some psychophysiological features of REM sleep were examined in REM-onset (without any preceding delta sleep--\"early REM period\") and in the REM period (REMP) terminating the normal sleep cycle (with the preceding delta sleep) of 92 daytime sleep attacks in 10 narcoleptic patients. Under these conditions the significant differences exist in the characteristics of the dream reports and in subjective estimations of sleep quality and duration. Sleep was evaluated as \"superficial\" and underestimations of sleep duration took place after an early REMP. Correct estimations of sleep duration and evaluations of sleep as \"deep\" dominated after REMP enging sleep cycles. The results obtained indicate the functional interaction between the delta sleep and REM sleep existing in the sleep cycle and largely determining the psychic content of the brain activity in the REM sleep."} {"id": "PMID:172170", "title": "Determination of isozymes of phosphoglycerate-mutase (E.C.2.7.5.3) and enolase (E.C.4.2.1.11) in human erythrocytes.", "content": "525 human hemolysates were tested for the isozymic patterns of phosphoglycerate mutase and enolase. Genetic models for interpreting the pherograms are suggested.", "contents": "Determination of isozymes of phosphoglycerate-mutase (E.C.2.7.5.3) and enolase (E.C.4.2.1.11) in human erythrocytes. 525 human hemolysates were tested for the isozymic patterns of phosphoglycerate mutase and enolase. Genetic models for interpreting the pherograms are suggested."} {"id": "PMID:172174", "title": "Dorsal thumb flap for release of adduction contracture of the first web space.", "content": "A local flap, utilizing the skin over the dorsum of the thumb, for release of a first web space contracture has been described. Its construction allows for full integumentary release, adequate visualization of underlying contracted tissues, and a closure that provides full thickness sensory skin coverage over the entire web space and key pinch contact area.", "contents": "Dorsal thumb flap for release of adduction contracture of the first web space. A local flap, utilizing the skin over the dorsum of the thumb, for release of a first web space contracture has been described. Its construction allows for full integumentary release, adequate visualization of underlying contracted tissues, and a closure that provides full thickness sensory skin coverage over the entire web space and key pinch contact area."} {"id": "PMID:172171", "title": "[Cytological aspects of various particular varieties of breast epitheliomas].", "content": "Needle aspiration for cytological investigation has been used at the Foundation Curie since 1954. Until 1973, no less than 3,176 mammary tumours have been studied by this method and comparison made with the histological findings. In the whole group some relatively rare carcinomas have been encountered -- mucoid, medullary, adenoid cystic, squamous and apocrine. Each category is described from the cytologic viewpoint and illustrated with an appropriate cyto/histologic example to show what a high degree of precision may be attained by diagnostic cytology in mammary cancer.", "contents": "[Cytological aspects of various particular varieties of breast epitheliomas]. Needle aspiration for cytological investigation has been used at the Foundation Curie since 1954. Until 1973, no less than 3,176 mammary tumours have been studied by this method and comparison made with the histological findings. In the whole group some relatively rare carcinomas have been encountered -- mucoid, medullary, adenoid cystic, squamous and apocrine. Each category is described from the cytologic viewpoint and illustrated with an appropriate cyto/histologic example to show what a high degree of precision may be attained by diagnostic cytology in mammary cancer."} {"id": "PMID:172172", "title": "[Immunovirological factors in epitheliomas of the rhinopharynx].", "content": "The epidemiology of nasopharyngeal carcinoma (NPC) suggests the intervention of genetic factors. These factors may be represented by a specific HL-A pattern (leucocyte antigens) as found in Chinese NPC patients (deficit of antigens corresponding to the second sublocus and discovery of a new antigen, named SIN-2). The association between NPC and a herpesvirus (the EBV) is based on elevated antibodies against a variety of EBV coded antigens, on cell mediated immune reactions, and on the regular presence of viral fingerprints in the epithelial tumour cells (viral DNA and nuclear antigen -- EBNA). The serological profile should help to establish the diagnosis of NPC in certain cases. The association between genetic factors, a herpesvirus and a human tumour represents a unique model in human cancer research.", "contents": "[Immunovirological factors in epitheliomas of the rhinopharynx]. The epidemiology of nasopharyngeal carcinoma (NPC) suggests the intervention of genetic factors. These factors may be represented by a specific HL-A pattern (leucocyte antigens) as found in Chinese NPC patients (deficit of antigens corresponding to the second sublocus and discovery of a new antigen, named SIN-2). The association between NPC and a herpesvirus (the EBV) is based on elevated antibodies against a variety of EBV coded antigens, on cell mediated immune reactions, and on the regular presence of viral fingerprints in the epithelial tumour cells (viral DNA and nuclear antigen -- EBNA). The serological profile should help to establish the diagnosis of NPC in certain cases. The association between genetic factors, a herpesvirus and a human tumour represents a unique model in human cancer research."} {"id": "PMID:172181", "title": "Effects of \"natural oestrogen\" replacement therapy on menopausal symptoms and blood clotting.", "content": "In a double-blind study on the value of equine (\"natural\") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.", "contents": "Effects of \"natural oestrogen\" replacement therapy on menopausal symptoms and blood clotting. In a double-blind study on the value of equine (\"natural\") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended."} {"id": "PMID:172183", "title": "Viruses and the aetiology of diabetes: a study in identical twins.", "content": "Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins.", "contents": "Viruses and the aetiology of diabetes: a study in identical twins. Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins."} {"id": "PMID:172187", "title": "Histological evidence of carcinoma in a hepatic tumour associated with oral contraceptives.", "content": "A primary hepatic tumour occurred in a 21-year-old woman who had been taking oral contraceptives for two years; she was treated by partial hepatectomy. Part of the neoplasm showed features suggestive of focal nodular hyperplasia, while the remainder had the histological characteristics of a well-differentiated hepatocellular carcinoma. This is the first report of malignant transformation of a tumour in a patient taking oral contraceptives.", "contents": "Histological evidence of carcinoma in a hepatic tumour associated with oral contraceptives. A primary hepatic tumour occurred in a 21-year-old woman who had been taking oral contraceptives for two years; she was treated by partial hepatectomy. Part of the neoplasm showed features suggestive of focal nodular hyperplasia, while the remainder had the histological characteristics of a well-differentiated hepatocellular carcinoma. This is the first report of malignant transformation of a tumour in a patient taking oral contraceptives."} {"id": "PMID:172188", "title": "Regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in type II hyperlipoproteinaemia.", "content": "The regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in leucocytes was studied in a family with familial type II hyperlipoproteinaemia (WHO classification). The propositus was heterozygous and 16 other members of the family were studied. Leucocytes were isolated by a relatively quick and simple procedure and used for enzyme estimations. The results suggest that measurement of the regulation of this enzyme in leucocytes may be helpful in the diagnosis and management of the condition.", "contents": "Regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in type II hyperlipoproteinaemia. The regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in leucocytes was studied in a family with familial type II hyperlipoproteinaemia (WHO classification). The propositus was heterozygous and 16 other members of the family were studied. Leucocytes were isolated by a relatively quick and simple procedure and used for enzyme estimations. The results suggest that measurement of the regulation of this enzyme in leucocytes may be helpful in the diagnosis and management of the condition."} {"id": "PMID:172190", "title": "Investigations on in vitro survival and virulence of T. pallidum under aerobiosis.", "content": "Motility of pathogenic T. pallidum was maintained in aerobic in vitro cultures for several weeks using a special medium. The latter consisted of McCoy's 5a medium supplemented with glutathione, sodium pyruvate, HEPES buffer, gentamycin (garamycin), and fetal calf serum. The virulence of the organisms was lost in 5 to 6 days. No multiplication of the organisms was observed. Four antibiotics (viomycin, kanamycin, gentamycin (garamycin), and neomycin) were tested for their bactericidal action and possible toxicity to T. pallidum. Gentamycin proved to be superior to the other three antibiotics in being non-toxic to the treponemes and showing a possible stimulatory effect on their motility and longevity. Cultivation of T. pallidum in cultured cells in the presence of the enzymes, superoxide dismutase and catalase, in a special medium showed possibilities for future experimentation under monitored, reduced oxygen pressure with a continuous system to dismutate superoxide radicals.", "contents": "Investigations on in vitro survival and virulence of T. pallidum under aerobiosis. Motility of pathogenic T. pallidum was maintained in aerobic in vitro cultures for several weeks using a special medium. The latter consisted of McCoy's 5a medium supplemented with glutathione, sodium pyruvate, HEPES buffer, gentamycin (garamycin), and fetal calf serum. The virulence of the organisms was lost in 5 to 6 days. No multiplication of the organisms was observed. Four antibiotics (viomycin, kanamycin, gentamycin (garamycin), and neomycin) were tested for their bactericidal action and possible toxicity to T. pallidum. Gentamycin proved to be superior to the other three antibiotics in being non-toxic to the treponemes and showing a possible stimulatory effect on their motility and longevity. Cultivation of T. pallidum in cultured cells in the presence of the enzymes, superoxide dismutase and catalase, in a special medium showed possibilities for future experimentation under monitored, reduced oxygen pressure with a continuous system to dismutate superoxide radicals."} {"id": "PMID:172191", "title": "Incidence of Herpesvirus hominis antibodies among blood donor populations.", "content": "The microneutralization test was used to determine the occurrence of antibodies to Herpesvirus hominis Type 1 and Type 2 in sera from patients attending the Special Clinic, Bristol Royal Infirmary, with proven herpes genitalis, and in sera taken from blood donors in Bath, Dursley, and Bristol, as well as from donors in three different prison populations. The findings in patients with herpes genitalis indicate that the test accurately reflects the antibody response expected in relation to the type of herpes virus isolated from the lesions. The incidence of Type 2 antibodies among the blood donors ranged from 5 per cent. for donors from the Bath area up to 60 per cent. among donors from Dartmoor prison. The findings suggested that Type 2 herpes infection could spread among longterm prison populations, and it is postulated that this may be due to both homosexual contact, and also by non-sexual contact, either directly or via fomites.", "contents": "Incidence of Herpesvirus hominis antibodies among blood donor populations. The microneutralization test was used to determine the occurrence of antibodies to Herpesvirus hominis Type 1 and Type 2 in sera from patients attending the Special Clinic, Bristol Royal Infirmary, with proven herpes genitalis, and in sera taken from blood donors in Bath, Dursley, and Bristol, as well as from donors in three different prison populations. The findings in patients with herpes genitalis indicate that the test accurately reflects the antibody response expected in relation to the type of herpes virus isolated from the lesions. The incidence of Type 2 antibodies among the blood donors ranged from 5 per cent. for donors from the Bath area up to 60 per cent. among donors from Dartmoor prison. The findings suggested that Type 2 herpes infection could spread among longterm prison populations, and it is postulated that this may be due to both homosexual contact, and also by non-sexual contact, either directly or via fomites."} {"id": "PMID:172193", "title": "An androgen receptor in rat brain and pituitary.", "content": "Dihydrotestosterone (DHT) binding was measured in cytosols from brain regions and pituitary of adult female rats and, with the addition of ventral prostate, in adult male rats. Two types of binding were distinguished: one, saturable at concentration of DHT greater than or equal to 5 X 10(-9) M and an unsaturable component. In intact males saturable (limited capacity) binding was detected only in ventral prostate cytosol; 3 days after orchidectomy the saturable binding sites increase 3-fold in prostate and in pituitary, hypothalamus, amygdala and cortex to detectable levels in approximately the same abundance as in females. There were significant differences in the affinities of the limited capacity binding reactions in cytosols of different tissues though all were in the order of magnitude, 10(-9) M DHT. The affinity in pituitary cytosol was lower than in brain regions with the single exception of female amygdala in which the affinity was significantly lower than in cytosol of the same region from 3-day castrate males. The specificity of the limited capacity binding was investigated by competition between [3h]DHT and unlabelled steroids; the most effective competitors were potent androgen agonists and antagonists.", "contents": "An androgen receptor in rat brain and pituitary. Dihydrotestosterone (DHT) binding was measured in cytosols from brain regions and pituitary of adult female rats and, with the addition of ventral prostate, in adult male rats. Two types of binding were distinguished: one, saturable at concentration of DHT greater than or equal to 5 X 10(-9) M and an unsaturable component. In intact males saturable (limited capacity) binding was detected only in ventral prostate cytosol; 3 days after orchidectomy the saturable binding sites increase 3-fold in prostate and in pituitary, hypothalamus, amygdala and cortex to detectable levels in approximately the same abundance as in females. There were significant differences in the affinities of the limited capacity binding reactions in cytosols of different tissues though all were in the order of magnitude, 10(-9) M DHT. The affinity in pituitary cytosol was lower than in brain regions with the single exception of female amygdala in which the affinity was significantly lower than in cytosol of the same region from 3-day castrate males. The specificity of the limited capacity binding was investigated by competition between [3h]DHT and unlabelled steroids; the most effective competitors were potent androgen agonists and antagonists."} {"id": "PMID:172194", "title": "Direction-selective units in the rabbit's nucleus of the optic tract.", "content": "A class of direction-selective (DS) units, histologically localized within the nucleus of the optic tract (NOT) was isolated in the rabbit's pretectum. These units typically had a maintained discharge of 25-50 action potentials/sec and large receptive fields (up to 40 X 150 degrees) in the visual streak area of the contralateral eye. They were excited by a visual pattern moving in one direction and inhibited by motion in the opposite direction. The reactions were sustained. Excitatory and inhibitory acceptance angles were each 180 degrees. Most units were excited by anterior motion of the stimulus and reacted to a wide range of velocities (0.01-20 degrees/sec). Random checkerboard patterns (elements 0.8 degrees), grids of black and white stripes (1, 2 and 4 degrees wide) and single black and white edges were all effective, with a decreasing response magnitude in roughly this order. A stimulus area of 2 X 2 degrees was already effective; response increased with area and was maximal for 15 X 15 degrees and larger stimuli. Latency for visual stimulation was 60 +/- 10 (S.D.) msec, for electrical stimulation of the chiasm 2.2 +/- 0.3 (S.D.) msec. Synaptic latency and presynaptic conduction velocity were estimated at 0.7 msec and 13m/sec, respectively. A strong convergence of retinal DS fibers upon NOT units is postulated. Since most properties of NOT units are compatible with those of optokinetic nystagmus, and electrical stimulation of the NOT elicits vigorous nystagmus, these data suggest that these cells are the essential afferent link in the optokinetic reflex arc.", "contents": "Direction-selective units in the rabbit's nucleus of the optic tract. A class of direction-selective (DS) units, histologically localized within the nucleus of the optic tract (NOT) was isolated in the rabbit's pretectum. These units typically had a maintained discharge of 25-50 action potentials/sec and large receptive fields (up to 40 X 150 degrees) in the visual streak area of the contralateral eye. They were excited by a visual pattern moving in one direction and inhibited by motion in the opposite direction. The reactions were sustained. Excitatory and inhibitory acceptance angles were each 180 degrees. Most units were excited by anterior motion of the stimulus and reacted to a wide range of velocities (0.01-20 degrees/sec). Random checkerboard patterns (elements 0.8 degrees), grids of black and white stripes (1, 2 and 4 degrees wide) and single black and white edges were all effective, with a decreasing response magnitude in roughly this order. A stimulus area of 2 X 2 degrees was already effective; response increased with area and was maximal for 15 X 15 degrees and larger stimuli. Latency for visual stimulation was 60 +/- 10 (S.D.) msec, for electrical stimulation of the chiasm 2.2 +/- 0.3 (S.D.) msec. Synaptic latency and presynaptic conduction velocity were estimated at 0.7 msec and 13m/sec, respectively. A strong convergence of retinal DS fibers upon NOT units is postulated. Since most properties of NOT units are compatible with those of optokinetic nystagmus, and electrical stimulation of the NOT elicits vigorous nystagmus, these data suggest that these cells are the essential afferent link in the optokinetic reflex arc."} {"id": "PMID:172195", "title": "[Evolution of visual evoked responses during various states of vigilance in Papio papio (author's transl)].", "content": "Averaged evoked responses (AER) to light flashes were recorded in baboons (Papio papio) during wakefulness, slow-wave sleep and rapid eye movement (REM) periods, at the visual cortex, retrocalcarine sulcus, optic tract (OT), lateral geniculate (LG) and pulvinar. Waking AERs were composed: in the OT, of a negative, low amplitude wave at 13.3 msec (I), a high amplitude wave at 34.8 msec (II), a negative wave at 72 msec (III) and a late component at 151 msec; in the LG, a small positive wave (II) with a peak latency of 40 msec, a high amplitude negative wave (III) with a latency of 70 msec and a late component; in the pulvinar of two low amplitude short latency waves (I and II), respectively negative and positive at 25 msec and 40 msec, then a high amplitude negative wave (III) at 75 msec and a late component; in the retrocalcarine sulcus 3 positive waves (I, II and III) were recorded at 25, 45 and 100 msec and a late component; in the visual cortex, 3 low amplitude negative waves (II, III and IV at 40, 50 and 54 msec, then a positive wave at 80 msec and some late components. In slow-wave sleep, AERs did not change in the OT, but in the LG and pulvinar, they showed an increase in the amplitude of wave II from stage 1 to stage 3. At the cortical level, early waves (II for the retrocalcarine sulcus, II and IV for the visual cortex) presented a marked increase in amplitude during stages 2 and 3, but only a slight increase for stage 1. Peak latency increase of each wave in cortical and subcortical AERs was seen during slow-wave sleep. REM AERs resembled, in amplitude and peak latency, those recorded in the LG and pulvinar during wakefulness; in the visual cortex and retrocalcarine sulcus, they were similar to those obtained during wakefulness and stage 1. In conclusion, a different evoked response was found between visual cortex and deep structures (except for the OT): firstly, during slow-wave sleep (the AERs showed a difference for stage 1 between the visual cortex or the retrocalcarine sulcus and the LG or the pulvinar), secondly, in REM (on the cortex, REM AERs looked like wakefulness and stage 1 responses); on the contrary, in the LG and pulvinar, REM AERs were similar only to those recorded during waking. Finally, it can be said that for Papio papio the differentiation and structural responses between the various stages of sleep (particularly light sleep and REM) were greater in the cortex than in the thalamic structures.", "contents": "[Evolution of visual evoked responses during various states of vigilance in Papio papio (author's transl)]. Averaged evoked responses (AER) to light flashes were recorded in baboons (Papio papio) during wakefulness, slow-wave sleep and rapid eye movement (REM) periods, at the visual cortex, retrocalcarine sulcus, optic tract (OT), lateral geniculate (LG) and pulvinar. Waking AERs were composed: in the OT, of a negative, low amplitude wave at 13.3 msec (I), a high amplitude wave at 34.8 msec (II), a negative wave at 72 msec (III) and a late component at 151 msec; in the LG, a small positive wave (II) with a peak latency of 40 msec, a high amplitude negative wave (III) with a latency of 70 msec and a late component; in the pulvinar of two low amplitude short latency waves (I and II), respectively negative and positive at 25 msec and 40 msec, then a high amplitude negative wave (III) at 75 msec and a late component; in the retrocalcarine sulcus 3 positive waves (I, II and III) were recorded at 25, 45 and 100 msec and a late component; in the visual cortex, 3 low amplitude negative waves (II, III and IV at 40, 50 and 54 msec, then a positive wave at 80 msec and some late components. In slow-wave sleep, AERs did not change in the OT, but in the LG and pulvinar, they showed an increase in the amplitude of wave II from stage 1 to stage 3. At the cortical level, early waves (II for the retrocalcarine sulcus, II and IV for the visual cortex) presented a marked increase in amplitude during stages 2 and 3, but only a slight increase for stage 1. Peak latency increase of each wave in cortical and subcortical AERs was seen during slow-wave sleep. REM AERs resembled, in amplitude and peak latency, those recorded in the LG and pulvinar during wakefulness; in the visual cortex and retrocalcarine sulcus, they were similar to those obtained during wakefulness and stage 1. In conclusion, a different evoked response was found between visual cortex and deep structures (except for the OT): firstly, during slow-wave sleep (the AERs showed a difference for stage 1 between the visual cortex or the retrocalcarine sulcus and the LG or the pulvinar), secondly, in REM (on the cortex, REM AERs looked like wakefulness and stage 1 responses); on the contrary, in the LG and pulvinar, REM AERs were similar only to those recorded during waking. Finally, it can be said that for Papio papio the differentiation and structural responses between the various stages of sleep (particularly light sleep and REM) were greater in the cortex than in the thalamic structures."} {"id": "PMID:172199", "title": "An ultrastructural study of the articular cartilage in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (chondrocalcinosis articularis).", "content": "An ultrastructural study of articular cartilage from five patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was performed. The CPPD crystals, identified by micro X-ray diffraction, were usually found in clusters, located in intercellular areas of the intermediate cartilage layer. The matrix surrounding the clusters either showed a normal morphology or a homogeneous appearance, within which faint cross striations but no distinctly fibrillar outlines could be identified. Another change in the matrix, characterized by an increased electron density and longitudinally fragmented collagen fibres, was also seen. This latter change was generally seen without concomitant CPPD crystal deposition. No specific relationship between the crystals and the collagen fibres or the granular background material of the matrix was encountered.", "contents": "An ultrastructural study of the articular cartilage in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (chondrocalcinosis articularis). An ultrastructural study of articular cartilage from five patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was performed. The CPPD crystals, identified by micro X-ray diffraction, were usually found in clusters, located in intercellular areas of the intermediate cartilage layer. The matrix surrounding the clusters either showed a normal morphology or a homogeneous appearance, within which faint cross striations but no distinctly fibrillar outlines could be identified. Another change in the matrix, characterized by an increased electron density and longitudinally fragmented collagen fibres, was also seen. This latter change was generally seen without concomitant CPPD crystal deposition. No specific relationship between the crystals and the collagen fibres or the granular background material of the matrix was encountered."} {"id": "PMID:172200", "title": "Comparative enzymatic properties of avian liver and skeletal muscle D-fructose-1,6-bisphosphate 1-phosphohydrolase.", "content": "The enzymatic properties of purified preparations of chicken liver and chicken skeletal muscle fructose bisphosphatases (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) were compared. Both enzymes have an absolute requirement for Mg2+ or Mn2+. The apparent Km for MgCl2 at pH 7.5 was 0.5 mM for the muscle enzyme and 5 mM for the liver enzyme. Fructose bisphosphate inhibited both enzymes. At pH 7.5, the inhibitor constants (Ki) were 0.18 and 1.3 mM for muscle and liver fructose bisphosphatases, respectively. The muscle enzyme was considerably more sensitive to AMP inhibition than the liver enzyme. At pH 7.5 and in the presence of 1 mM MgCl2, 50% inhibition of muscle and liver fructose bisphosphatases occurred at AMP concentrations of 7 X 10(-9) and 1 X 10(-6) M, respectively. EDTA activated both enzymes. The degree of activation was time and concentration dependent. The degree of EDTA activation of both enzymes decreased with increasing MgCl2 concentration. Ca2+ was a potent inhibitor of both liver (Ki, 1 X 10(-4) M) and muscle (Ki, 1 X 10(-5) M) fructose bisphosphatase. This inhibition was reversed by the presence of EDTA. Ca2+ appears to be a competitive inhibitor with regard to Mg2+. There is, however, a positive homeotropic interaction among Mg2+ sites of both enzymes in the presence of Ca2+.", "contents": "Comparative enzymatic properties of avian liver and skeletal muscle D-fructose-1,6-bisphosphate 1-phosphohydrolase. The enzymatic properties of purified preparations of chicken liver and chicken skeletal muscle fructose bisphosphatases (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) were compared. Both enzymes have an absolute requirement for Mg2+ or Mn2+. The apparent Km for MgCl2 at pH 7.5 was 0.5 mM for the muscle enzyme and 5 mM for the liver enzyme. Fructose bisphosphate inhibited both enzymes. At pH 7.5, the inhibitor constants (Ki) were 0.18 and 1.3 mM for muscle and liver fructose bisphosphatases, respectively. The muscle enzyme was considerably more sensitive to AMP inhibition than the liver enzyme. At pH 7.5 and in the presence of 1 mM MgCl2, 50% inhibition of muscle and liver fructose bisphosphatases occurred at AMP concentrations of 7 X 10(-9) and 1 X 10(-6) M, respectively. EDTA activated both enzymes. The degree of activation was time and concentration dependent. The degree of EDTA activation of both enzymes decreased with increasing MgCl2 concentration. Ca2+ was a potent inhibitor of both liver (Ki, 1 X 10(-4) M) and muscle (Ki, 1 X 10(-5) M) fructose bisphosphatase. This inhibition was reversed by the presence of EDTA. Ca2+ appears to be a competitive inhibitor with regard to Mg2+. There is, however, a positive homeotropic interaction among Mg2+ sites of both enzymes in the presence of Ca2+."} {"id": "PMID:172201", "title": "Polypeptide hormone receptors: characteristics and applications.", "content": "Major developments in the area of polypeptide hormone receptors have been reviewed. Receptors are high affinity, high specificity binding sites which appear to be located largely, if not entirely, on the plasma membrane of cells. Receptors are proteins intimately associated with and influenced by lipids. Receptor sites and degrading sites appear to be readily distinguishable entities. The binding of hormone to receptor is distinct and has been dissociated from subsequent steps leading to hormonal response. There is no direct relationship between receptor occupancy and the magnitude of target response to hormone. So called 'spare' receptors can be viewed thermodynamically as enhancing target tissue sensitivity to hormone. The binding of hormone to receptor appears to be a point at which regulation of tissue sensitivity can be influenced either through altering the affinity for hormone or the number of receptors. One factor apparently involved in the regulation of receptor levels is the hormone itself. Receptors have been used to develop assay procedures which have significantly complemented the bioassay and radioimmunoassay. Finally, the measurement of receptor levels in disease has provided new insights into pathophysiology.", "contents": "Polypeptide hormone receptors: characteristics and applications. Major developments in the area of polypeptide hormone receptors have been reviewed. Receptors are high affinity, high specificity binding sites which appear to be located largely, if not entirely, on the plasma membrane of cells. Receptors are proteins intimately associated with and influenced by lipids. Receptor sites and degrading sites appear to be readily distinguishable entities. The binding of hormone to receptor is distinct and has been dissociated from subsequent steps leading to hormonal response. There is no direct relationship between receptor occupancy and the magnitude of target response to hormone. So called 'spare' receptors can be viewed thermodynamically as enhancing target tissue sensitivity to hormone. The binding of hormone to receptor appears to be a point at which regulation of tissue sensitivity can be influenced either through altering the affinity for hormone or the number of receptors. One factor apparently involved in the regulation of receptor levels is the hormone itself. Receptors have been used to develop assay procedures which have significantly complemented the bioassay and radioimmunoassay. Finally, the measurement of receptor levels in disease has provided new insights into pathophysiology."} {"id": "PMID:172202", "title": "Effect of temperature on the activity and synthesis of glucose-catabolizing enzymes in Pseudomonas fluorescens.", "content": "The activity of the enzymes of the oxidative non-phosphorylated pathway, glucose and gluconate dehydrogenases, were not significantly affected by changes in the assay temperature. Both enzymes demonstrated only a threefold difference in activity when compared at assay temperatures of 30 degrees C and 5 degrees C. In contrast, the enzymes involved in the direct phosphorylation and catabolism of glucose or its oxidation products, gluconate and 2-ketogluconate, exhibited a more pronounced response to decreasing assay temperatures. At least one enzyme in each pathway, involved in the direct phosphorylation and catabolism of glucose or 2-ketogluconate (2KG), demonstrated an eightfold decrease in activity with a decrease in assay temperature from 30 degrees C to 5 degrees C. A similar decrease in assay temperature resulted in a fivefold decrease in activity of the enzymes involved in the direct phosphorylation and catabolism of gluconate. The observed differential effect of temperature on the activity of the enzymes of glucose catabolism and on the accumulation of direct oxidation products during growth with glucose in P. fluorescens E-20 is discussed. Growth with glucose at 5 or 20 degrees C resulted in high induced levels of all glucose-catabolizing enzymes examined when compared with the levels of these same enzymes in pyruvate-grown cells. However, only low levels of glucose dehydrogenase were detected during growth at 30 degrees C with glucose, gluconate, or 2-KG. Similarly, only low levels of gluconate dehydrogenase were detected during growth with glucose at 30 degrees C, although a weak induction was observed during growth with gluconate or 2-KG at 30 degrees C. The levels of 2-KG kinase plus KPG reductase during growth at 30 degrees C were undetectable with glucose, weakly induced with gluconate, and fully induced with 2-KG. High induced levels of glucose dehydrogenase, gluconate dehydrogenase, and 2-KG kinase plus KPG reductase were present during growth at 20 degrees C with glucose or 2-KG. The low levels of glucose and gluconate dehydrogenases present at a growth temperature of 30 degrees C was not due to heat lability of the enzymes at this temperature. The low amounts of these two enzymes during growth with glucose at 30 degrees C probably prevented sufficient inducer(s) formation from glucose to allow induction of enzymes of 2-KG catabolism. The results demonstrated that temperature may regulate the pathways of glucose dissimilation by regulating, either directly or indirectly, the activity and synthesis of the enzymes involved in these pathways.", "contents": "Effect of temperature on the activity and synthesis of glucose-catabolizing enzymes in Pseudomonas fluorescens. The activity of the enzymes of the oxidative non-phosphorylated pathway, glucose and gluconate dehydrogenases, were not significantly affected by changes in the assay temperature. Both enzymes demonstrated only a threefold difference in activity when compared at assay temperatures of 30 degrees C and 5 degrees C. In contrast, the enzymes involved in the direct phosphorylation and catabolism of glucose or its oxidation products, gluconate and 2-ketogluconate, exhibited a more pronounced response to decreasing assay temperatures. At least one enzyme in each pathway, involved in the direct phosphorylation and catabolism of glucose or 2-ketogluconate (2KG), demonstrated an eightfold decrease in activity with a decrease in assay temperature from 30 degrees C to 5 degrees C. A similar decrease in assay temperature resulted in a fivefold decrease in activity of the enzymes involved in the direct phosphorylation and catabolism of gluconate. The observed differential effect of temperature on the activity of the enzymes of glucose catabolism and on the accumulation of direct oxidation products during growth with glucose in P. fluorescens E-20 is discussed. Growth with glucose at 5 or 20 degrees C resulted in high induced levels of all glucose-catabolizing enzymes examined when compared with the levels of these same enzymes in pyruvate-grown cells. However, only low levels of glucose dehydrogenase were detected during growth at 30 degrees C with glucose, gluconate, or 2-KG. Similarly, only low levels of gluconate dehydrogenase were detected during growth with glucose at 30 degrees C, although a weak induction was observed during growth with gluconate or 2-KG at 30 degrees C. The levels of 2-KG kinase plus KPG reductase during growth at 30 degrees C were undetectable with glucose, weakly induced with gluconate, and fully induced with 2-KG. High induced levels of glucose dehydrogenase, gluconate dehydrogenase, and 2-KG kinase plus KPG reductase were present during growth at 20 degrees C with glucose or 2-KG. The low levels of glucose and gluconate dehydrogenases present at a growth temperature of 30 degrees C was not due to heat lability of the enzymes at this temperature. The low amounts of these two enzymes during growth with glucose at 30 degrees C probably prevented sufficient inducer(s) formation from glucose to allow induction of enzymes of 2-KG catabolism. The results demonstrated that temperature may regulate the pathways of glucose dissimilation by regulating, either directly or indirectly, the activity and synthesis of the enzymes involved in these pathways."} {"id": "PMID:172203", "title": "Immunochemical studies of the surface and cytoplasmic membranes of Entamoeba invadens (Rodhain 1934).", "content": "The antigenic properties of cell fractions prepared from axenically grown Entamoeba invadens were investigated using various immunoelectrophoretic methods. All membrane fractions displayed varying degrees of antigenicity, the most predominant being a cytoplasmic light-vesicle fraction. The surface membrane showed the least diversified range of antigenic components and was also the least immunogenic fraction as judged by the reactivity of the antisera produced. Using tandem-crossed immunoelectrophoresis the antigenic profiles of the membrane fractions were compared. No evidence was obtained for the presence of either lipid or carbohydrate in the antigenic moieties of any of the membrane fractions. Using a series of sequential solvent extractions it was concluded that both divalent metallochelate linkages and interiorly located hydrophobic associations were principally involved in binding the major antigenic components within the light-vesicle membrane. An enzymic function was assigned to certain of the membrane antigens, the immunoprecipitates obtained showing both acid phosphohydrolase and non-specific esterase acitivity toward a variety of substrates.", "contents": "Immunochemical studies of the surface and cytoplasmic membranes of Entamoeba invadens (Rodhain 1934). The antigenic properties of cell fractions prepared from axenically grown Entamoeba invadens were investigated using various immunoelectrophoretic methods. All membrane fractions displayed varying degrees of antigenicity, the most predominant being a cytoplasmic light-vesicle fraction. The surface membrane showed the least diversified range of antigenic components and was also the least immunogenic fraction as judged by the reactivity of the antisera produced. Using tandem-crossed immunoelectrophoresis the antigenic profiles of the membrane fractions were compared. No evidence was obtained for the presence of either lipid or carbohydrate in the antigenic moieties of any of the membrane fractions. Using a series of sequential solvent extractions it was concluded that both divalent metallochelate linkages and interiorly located hydrophobic associations were principally involved in binding the major antigenic components within the light-vesicle membrane. An enzymic function was assigned to certain of the membrane antigens, the immunoprecipitates obtained showing both acid phosphohydrolase and non-specific esterase acitivity toward a variety of substrates."} {"id": "PMID:172204", "title": "Pathways of carbohydrate metabolism in mycobacterium tuberculosis H37Rv1.", "content": "Radiorespirometric studies using glucose labelled at 1, 2, 3-4, and 6 positions and enzymatic studies were conducted to determine the primary pathways of glucose dissimilation in Mycobacterium tuberculosis H37Rv. The pattern of 14CO2 recovery was C3-4 greater than C1 greater than C6 = C2. The Embden-Meyerhof pathway was found to be the predominant pathway for glucose oxidation, operative to the extent of 94%. The pentose phosphate pathway accounted for the remaining 6%. Maximum incorporation of 14C into cellular components was from C2 and C6 labelled glucose.", "contents": "Pathways of carbohydrate metabolism in mycobacterium tuberculosis H37Rv1. Radiorespirometric studies using glucose labelled at 1, 2, 3-4, and 6 positions and enzymatic studies were conducted to determine the primary pathways of glucose dissimilation in Mycobacterium tuberculosis H37Rv. The pattern of 14CO2 recovery was C3-4 greater than C1 greater than C6 = C2. The Embden-Meyerhof pathway was found to be the predominant pathway for glucose oxidation, operative to the extent of 94%. The pentose phosphate pathway accounted for the remaining 6%. Maximum incorporation of 14C into cellular components was from C2 and C6 labelled glucose."} {"id": "PMID:172205", "title": "A comparative study on the heat stability of triosephosphate isomerase in psychrophilic, psychrotrophic, and mesophilic clostridia.", "content": "The temperature stability of triosephosphate isomerase (EC 5.3.1.1) in the cell-free extracts of psychrophilic, psychrotrophic, and mesophilic Clostridium species has been investigated. Even though this enzyme was found to be heat labile in the psychrophilic isolates, no detectable loss in activity was evident when cell-free extracts were heated for 1/2 h at the maximum temperature of growth for the organisms. Two organisms, each with a maximum growth temperature of 23 degrees C, showed different heat stability of triosephosphate isomerase. However, a trend is evident that as the maximum growth temperature increases, the thermostability also increases. It is suggested that the heat liability of this enzyme is not a controlling factor in psychrophilism, but rather an adaptation to the cold habitat of these organisms.", "contents": "A comparative study on the heat stability of triosephosphate isomerase in psychrophilic, psychrotrophic, and mesophilic clostridia. The temperature stability of triosephosphate isomerase (EC 5.3.1.1) in the cell-free extracts of psychrophilic, psychrotrophic, and mesophilic Clostridium species has been investigated. Even though this enzyme was found to be heat labile in the psychrophilic isolates, no detectable loss in activity was evident when cell-free extracts were heated for 1/2 h at the maximum temperature of growth for the organisms. Two organisms, each with a maximum growth temperature of 23 degrees C, showed different heat stability of triosephosphate isomerase. However, a trend is evident that as the maximum growth temperature increases, the thermostability also increases. It is suggested that the heat liability of this enzyme is not a controlling factor in psychrophilism, but rather an adaptation to the cold habitat of these organisms."} {"id": "PMID:172206", "title": "Electron microscopy of vesicular-arbuscular mycorrhizae of yellow poplar. II. Intracellular hyphae and vesicles.", "content": "Intracellular hyphae and vesicles in mycorrhizal roots of yellow poplar were examined by electron microscopy. An investing layer of host wall material and cytoplasm enclosed the endophyte within the cells. Young developing hyphae contained abundant cytoplasm and few vacuoles. As hyphae matured, they became highly vacuolated and accumulated carbohydrate (glycogen) and lipid reserves. Mature vesicles were engorged with lipid droplets, possessed a trilaminate wall and were also enclosed by host wall material and cytoplasm. Compared with uninfected cells, infected cortical cells showed an increase in cytoplasmic volume, enlarged nuclei, and a reduction of starch reserves. Host nuclei were always proximal to the hyphae during hyphal development and deterioration. While other cytoplasmic components of infected and uninfected cells were comparable large electron-dense bodies occurred in vacuoles of most cells containing hyphae. Deterioration of intracellular hyphae occurred throughout the samples examined. Septa separated functional and degenerating portions of the hyphae. Hyphal deterioration involved degeneration and ultimate disappearance of fungal cytoplasm as well as collapse of hyphal walls. Based on these observations, the authors hypothesize that deterioration of the endophyte may release significant quantities of mineral nutrients, via hyphal contents, which are absorbed by the host.", "contents": "Electron microscopy of vesicular-arbuscular mycorrhizae of yellow poplar. II. Intracellular hyphae and vesicles. Intracellular hyphae and vesicles in mycorrhizal roots of yellow poplar were examined by electron microscopy. An investing layer of host wall material and cytoplasm enclosed the endophyte within the cells. Young developing hyphae contained abundant cytoplasm and few vacuoles. As hyphae matured, they became highly vacuolated and accumulated carbohydrate (glycogen) and lipid reserves. Mature vesicles were engorged with lipid droplets, possessed a trilaminate wall and were also enclosed by host wall material and cytoplasm. Compared with uninfected cells, infected cortical cells showed an increase in cytoplasmic volume, enlarged nuclei, and a reduction of starch reserves. Host nuclei were always proximal to the hyphae during hyphal development and deterioration. While other cytoplasmic components of infected and uninfected cells were comparable large electron-dense bodies occurred in vacuoles of most cells containing hyphae. Deterioration of intracellular hyphae occurred throughout the samples examined. Septa separated functional and degenerating portions of the hyphae. Hyphal deterioration involved degeneration and ultimate disappearance of fungal cytoplasm as well as collapse of hyphal walls. Based on these observations, the authors hypothesize that deterioration of the endophyte may release significant quantities of mineral nutrients, via hyphal contents, which are absorbed by the host."} {"id": "PMID:172207", "title": "Bacterial growth in seafoood on restaurant premises.", "content": "Operational guidelines for a chain of the newer type of seafood restaurants and take-out stores were derived from plots of bacteriological and trimethylamine changes during the preparation and storage of cod fillets, shrimp, and clams. If fish is to be defrosted at room temperature it should be washed and portioned within 14 h. Subsequent storage at 5 degrees C should not exceed 72 h and once removed from the refrigerator it should be fried within 3 h. New stores should consider improved methods of defrosting. Trimethylamine content was a more sensitive measure of quality loss than bacterial growth. Shrimp quality can be improved by emphasizing the way shells are removed because most of the contamination was external. Shrimp shelled while still frozen had the best potential keeping quality. Clam meat is handled less and is always held at 5 degrees C; but bacterial growth indicated that it should not be held on the premises for more than 3 days including the time necessary for defrosting. Batter prepared fresh daily can be feft at room temperature. Frying can obliterate poor handling procedures, but adequate cooking is essential under any conditions. Clams are a gourmet item but the practice of cooking them lightly at customer request proved inadvisable.", "contents": "Bacterial growth in seafoood on restaurant premises. Operational guidelines for a chain of the newer type of seafood restaurants and take-out stores were derived from plots of bacteriological and trimethylamine changes during the preparation and storage of cod fillets, shrimp, and clams. If fish is to be defrosted at room temperature it should be washed and portioned within 14 h. Subsequent storage at 5 degrees C should not exceed 72 h and once removed from the refrigerator it should be fried within 3 h. New stores should consider improved methods of defrosting. Trimethylamine content was a more sensitive measure of quality loss than bacterial growth. Shrimp quality can be improved by emphasizing the way shells are removed because most of the contamination was external. Shrimp shelled while still frozen had the best potential keeping quality. Clam meat is handled less and is always held at 5 degrees C; but bacterial growth indicated that it should not be held on the premises for more than 3 days including the time necessary for defrosting. Batter prepared fresh daily can be feft at room temperature. Frying can obliterate poor handling procedures, but adequate cooking is essential under any conditions. Clams are a gourmet item but the practice of cooking them lightly at customer request proved inadvisable."} {"id": "PMID:172208", "title": "Kindling, unit discharge patterns and neural plasticity.", "content": "Two approaches to the study of the kindling phenomenon were discussed: 1) an attempt to identify the pattern of neural activity required to produce the changes underlying kindling and 2) an investigation into the nature of those changes. Three experiments were reported that used the neocortical transcallosal system as a monosynaptic model system in which to study possible synaptic mechanisms of the kindling effect. Experiment I showed an increase in the transcallosal evoked potential following neocortical kindling. Experiment II showed an increase in the strength of the transcallosal evoked cell discharge following neocortical kindling. Experiment III reported the results of an histological examination of neocortical tissue in kindled and non-kindled animals using the Golgi-Cox technique. Spine density, spine dimension and branching were measured for pyramidal cell apical dendrites. No differences were found between primary and secondary (contralateral) foci or between kindled and non-kindled animals.", "contents": "Kindling, unit discharge patterns and neural plasticity. Two approaches to the study of the kindling phenomenon were discussed: 1) an attempt to identify the pattern of neural activity required to produce the changes underlying kindling and 2) an investigation into the nature of those changes. Three experiments were reported that used the neocortical transcallosal system as a monosynaptic model system in which to study possible synaptic mechanisms of the kindling effect. Experiment I showed an increase in the transcallosal evoked potential following neocortical kindling. Experiment II showed an increase in the strength of the transcallosal evoked cell discharge following neocortical kindling. Experiment III reported the results of an histological examination of neocortical tissue in kindled and non-kindled animals using the Golgi-Cox technique. Spine density, spine dimension and branching were measured for pyramidal cell apical dendrites. No differences were found between primary and secondary (contralateral) foci or between kindled and non-kindled animals."} {"id": "PMID:172209", "title": "Behavioral and epileptic determinants of predatory attack behavior in the cat.", "content": "This report presents studies which relate limbic epileptic excitability to behavioral measures of defensive suppression of predatory attack in cats. Correlated with heightened defensiveness to environmental stimuli among non-killer cats is a heightened amygdaloid epileptic excitability, as well as a heightened conduction of amygdaloid epileptic activity to thalamic and hypothalamic substrates of predatory response in the amygdala to the complex visual stimuli presented by rat prey. These neurosensory responses correlate well with measures of epileptic excitability. Brain and behavior measures appear related since enhancement of excitability in the amygdala and of projection of epileptic activity by repeated electrical stimulation of predatory attacks. Furthermore, the ventral hippocampus seems capable of antagonizing the behaviorally suppressive effects of heightened amygdaloid excitability perhaps at points of convergence of amygdaloid and hippocampal output.", "contents": "Behavioral and epileptic determinants of predatory attack behavior in the cat. This report presents studies which relate limbic epileptic excitability to behavioral measures of defensive suppression of predatory attack in cats. Correlated with heightened defensiveness to environmental stimuli among non-killer cats is a heightened amygdaloid epileptic excitability, as well as a heightened conduction of amygdaloid epileptic activity to thalamic and hypothalamic substrates of predatory response in the amygdala to the complex visual stimuli presented by rat prey. These neurosensory responses correlate well with measures of epileptic excitability. Brain and behavior measures appear related since enhancement of excitability in the amygdala and of projection of epileptic activity by repeated electrical stimulation of predatory attacks. Furthermore, the ventral hippocampus seems capable of antagonizing the behaviorally suppressive effects of heightened amygdaloid excitability perhaps at points of convergence of amygdaloid and hippocampal output."} {"id": "PMID:172210", "title": "Frontal cortical kindling in cats.", "content": "Our observaiton of amygdoloid seizure development in cats indicated early afterdischarge propagation into basal cortical areas prior to the development of bifrontal sharp theta discharge. In view of the implied participation of the frontal lobe in amygdaloid kindling, both fractional lesioning and kindling of selective areas were performed. This paper summarizes out stimulation study involving premotor, prefrontal, mesial frontal and orbital cortices. Except for the orbital series which showed a rather strikingly similar pattern of seizure development to that of amygdaloid kindling, all areas showed significantly different features in terms of the speed of seizure development, afterdischarge propagation, fragility of developing seizure, final stage 5 seizure and post-ictal behavior pattern, interictal discharge morphology and propagation, and generalized seizure triggering threshold intensity. All these findings suggest that the frontal lobe participates in, but is not essential for, the amygdaloid seizure development. The results of ongoing fractional lesion series support such a conclusion.", "contents": "Frontal cortical kindling in cats. Our observaiton of amygdoloid seizure development in cats indicated early afterdischarge propagation into basal cortical areas prior to the development of bifrontal sharp theta discharge. In view of the implied participation of the frontal lobe in amygdaloid kindling, both fractional lesioning and kindling of selective areas were performed. This paper summarizes out stimulation study involving premotor, prefrontal, mesial frontal and orbital cortices. Except for the orbital series which showed a rather strikingly similar pattern of seizure development to that of amygdaloid kindling, all areas showed significantly different features in terms of the speed of seizure development, afterdischarge propagation, fragility of developing seizure, final stage 5 seizure and post-ictal behavior pattern, interictal discharge morphology and propagation, and generalized seizure triggering threshold intensity. All these findings suggest that the frontal lobe participates in, but is not essential for, the amygdaloid seizure development. The results of ongoing fractional lesion series support such a conclusion."} {"id": "PMID:172211", "title": "Frontal lobe and kindling in the rat.", "content": "To test the hypothesis that the cortex participates in amygdaloid kindling in rats, bilateral aspiration lesions were made in various cortical areas in rats prior to kindling. Lesions in orbital cortex (on the dorsal lip of the rhinal sulcus) or prefrontal cortex (area 10) significantly retarded the rate of amygdaloid kindling; lesions in motor cortex, anterior cingulate cortex, or visual cortex were without effect. Detailed analysis indicated that the orbital lesioned and frontal-lesioned rats kindled relatively normally up to the second-last stage of amygdaloid kindling, in which stage they perseverated significantly longer than the controls and the other lesioned rats. These results suggest that areas of the frontal lobe participate in the elaboration and generalization of amygdaloid seizures in rats. Although retarded in rate, kindling nonetheless occurred in the lesioned rats, indicating that these cortical areas are not essential for the development of amygdaloid seizures.", "contents": "Frontal lobe and kindling in the rat. To test the hypothesis that the cortex participates in amygdaloid kindling in rats, bilateral aspiration lesions were made in various cortical areas in rats prior to kindling. Lesions in orbital cortex (on the dorsal lip of the rhinal sulcus) or prefrontal cortex (area 10) significantly retarded the rate of amygdaloid kindling; lesions in motor cortex, anterior cingulate cortex, or visual cortex were without effect. Detailed analysis indicated that the orbital lesioned and frontal-lesioned rats kindled relatively normally up to the second-last stage of amygdaloid kindling, in which stage they perseverated significantly longer than the controls and the other lesioned rats. These results suggest that areas of the frontal lobe participate in the elaboration and generalization of amygdaloid seizures in rats. Although retarded in rate, kindling nonetheless occurred in the lesioned rats, indicating that these cortical areas are not essential for the development of amygdaloid seizures."} {"id": "PMID:172214", "title": "Cardiomyopathy after widely separated courses of adriamycin exacerbated by actinomycin-D and mithramycin.", "content": "A 22-year-old man with a synovial cell sarcoma attained an excellent response to therapy with adriamycin (NSC-123127) and dimethyltriazeno imidazole carboxamide (NSC-45388). Therapy was discontinued at a cumulative dose of adriamycin of 600 mg/m2. Relapse occurred 13 1/2 months later, and therapy with adriamycin was restarted. Because of tumor progression, therapy was discontinued after a cumulative dose of adriamycin of 120 mg/m2. Ten weeks later, severe congestive heart failure developed which ultimately caused the patient's death. Exacerbations of the heart failure were temporally related to the administration of the antitumor antibiotics actinomycin-D (NSC-3053) and mithramycin (NSC-24559). Electron microscopic examination of the heart revealed changes characteristic of adriamycin cardiomyopathy. Thus, even after a long hiatus, it may not be safe to exceed the recommended maximum cumulative dose level of adriamycin. The pathogenic mechanisms involved in the development of adriamycin cardiomyopathy are reviewed, and the possible synergistic effect of other antitumor antibiotics is discussed.", "contents": "Cardiomyopathy after widely separated courses of adriamycin exacerbated by actinomycin-D and mithramycin. A 22-year-old man with a synovial cell sarcoma attained an excellent response to therapy with adriamycin (NSC-123127) and dimethyltriazeno imidazole carboxamide (NSC-45388). Therapy was discontinued at a cumulative dose of adriamycin of 600 mg/m2. Relapse occurred 13 1/2 months later, and therapy with adriamycin was restarted. Because of tumor progression, therapy was discontinued after a cumulative dose of adriamycin of 120 mg/m2. Ten weeks later, severe congestive heart failure developed which ultimately caused the patient's death. Exacerbations of the heart failure were temporally related to the administration of the antitumor antibiotics actinomycin-D (NSC-3053) and mithramycin (NSC-24559). Electron microscopic examination of the heart revealed changes characteristic of adriamycin cardiomyopathy. Thus, even after a long hiatus, it may not be safe to exceed the recommended maximum cumulative dose level of adriamycin. The pathogenic mechanisms involved in the development of adriamycin cardiomyopathy are reviewed, and the possible synergistic effect of other antitumor antibiotics is discussed."} {"id": "PMID:172215", "title": "A laboratory model for the study of the immunobiology of osteosarcoma.", "content": "Inoculation of Moloney sarcoma virus into the marrow cavity of the tibia of newborn Wistar-Lewis rats resulted in the appearance of an initially localized osteosarcoma in 97.7% of these animals. At least 77.9% of the rats developed lung metastases and died, usually within 6 weeks of inoculation. The remaining 22.1% showed regression of disease after initial growth of the tumor. Tumor cells were maintained in tissue culture and used as target cells for a visual and isotopic (3H-thymidine or 125IUdR) microcytotoxicity assay. Cell-mediated immunity could be measured by these methods throughout the course of the illness in animals with progressive disease as well as in those whose tumors eventually regressed. The presence of serum factors capable of modifying the level of CMI was documented. This Moloney-sarcoma-virus-induced rat osteosarcoma and human osteosarcoma thus appear to have several basic pathologic and immunologic similarities. The model may be useful for studying the effects of a variety of treatment protocols upon the clinical course and immune response to osteosarcoma.", "contents": "A laboratory model for the study of the immunobiology of osteosarcoma. Inoculation of Moloney sarcoma virus into the marrow cavity of the tibia of newborn Wistar-Lewis rats resulted in the appearance of an initially localized osteosarcoma in 97.7% of these animals. At least 77.9% of the rats developed lung metastases and died, usually within 6 weeks of inoculation. The remaining 22.1% showed regression of disease after initial growth of the tumor. Tumor cells were maintained in tissue culture and used as target cells for a visual and isotopic (3H-thymidine or 125IUdR) microcytotoxicity assay. Cell-mediated immunity could be measured by these methods throughout the course of the illness in animals with progressive disease as well as in those whose tumors eventually regressed. The presence of serum factors capable of modifying the level of CMI was documented. This Moloney-sarcoma-virus-induced rat osteosarcoma and human osteosarcoma thus appear to have several basic pathologic and immunologic similarities. The model may be useful for studying the effects of a variety of treatment protocols upon the clinical course and immune response to osteosarcoma."} {"id": "PMID:172216", "title": "Antibodies to Epstein-Barr virus in patients with Hodgkin's disease and leukemia.", "content": "Sera from 67 Hodgkin's disease patients, 71 leukemia patients, and 186 healthy subjects were tested for antibodies to Epstein-Barr (EB) viral antigens by immunofluorescence methods. In both disease categories, in particular Hodgkin's disease patients, levels of antibodies to the viral capsid antigen (EBV-VCA) and MGT were higher than in the healthy controls. Significantly higher titers were found in Jewish patients of Asian-African origin, as compared to Jews of European origin, with Arab patients as intermediates. The effect of ethnic origin was independant of age and histopathologic type. Sex had no effect on titer. Inconsistent differences in titer were found between age groups in the various ethnic-histopathologic type groups. Some of the leukemia patients had no detectable antibodies to EBV, while all Hodgkin's disease patients showed previous contact with EB virus. Antibodies to the early antigen (EBV-EA) were found in 27% of Hodgkin's and 37% of leukemia patients, and in none of the healthy controls tested.", "contents": "Antibodies to Epstein-Barr virus in patients with Hodgkin's disease and leukemia. Sera from 67 Hodgkin's disease patients, 71 leukemia patients, and 186 healthy subjects were tested for antibodies to Epstein-Barr (EB) viral antigens by immunofluorescence methods. In both disease categories, in particular Hodgkin's disease patients, levels of antibodies to the viral capsid antigen (EBV-VCA) and MGT were higher than in the healthy controls. Significantly higher titers were found in Jewish patients of Asian-African origin, as compared to Jews of European origin, with Arab patients as intermediates. The effect of ethnic origin was independant of age and histopathologic type. Sex had no effect on titer. Inconsistent differences in titer were found between age groups in the various ethnic-histopathologic type groups. Some of the leukemia patients had no detectable antibodies to EBV, while all Hodgkin's disease patients showed previous contact with EB virus. Antibodies to the early antigen (EBV-EA) were found in 27% of Hodgkin's and 37% of leukemia patients, and in none of the healthy controls tested."} {"id": "PMID:172217", "title": "Megavoltage irradiation in the treatment of gliomas of the brain and spinal cord.", "content": "Curative radiotherapy was attempted in treating 256 patients with unresected or partially excised gliomas of the brain and spinal cord. Survival decreased with increasing age, reflecting the different incidences of tumor types in various age groups. Actuarial 5-year survival ranged from 85% for cerebellar astrocytomas, to 47% for medulloblastomas, to 41% for cerebral hemispheric astrocytomas, and 0% for glioblastoma multiforme. Further improvements in survival utilizing radiotherapy are unlikely until new adjuncts are developed, for higher radiation doses may lead to a disproportionate increase in radiation complications.", "contents": "Megavoltage irradiation in the treatment of gliomas of the brain and spinal cord. Curative radiotherapy was attempted in treating 256 patients with unresected or partially excised gliomas of the brain and spinal cord. Survival decreased with increasing age, reflecting the different incidences of tumor types in various age groups. Actuarial 5-year survival ranged from 85% for cerebellar astrocytomas, to 47% for medulloblastomas, to 41% for cerebral hemispheric astrocytomas, and 0% for glioblastoma multiforme. Further improvements in survival utilizing radiotherapy are unlikely until new adjuncts are developed, for higher radiation doses may lead to a disproportionate increase in radiation complications."} {"id": "PMID:172218", "title": "Carcinoma of the cervix with cylindromatous features believed to arise in mesonerphric duct.", "content": "A detailed description of the clinical and morphological aspects of a case of carcinoma of the cervix arising from mesonephric duct remnants is presented, and the literature pertaining to these rare tumors is discussed. At the time of initial surgical treatment the tumor was confined to the cervix; however, eventual metastatic dissemination to the bony and soft tissues of the pelvis, the lungs, and the lower vertebral column resulted in the patient's death 8 years later. The tumor appeared refractory to further attempts at treatment with radiation, progestational therapy, and variety of chemotherapeutic agents. The observation of a focal cylindromatous growth pattern, not previously described in tumors of this type, is presented.", "contents": "Carcinoma of the cervix with cylindromatous features believed to arise in mesonerphric duct. A detailed description of the clinical and morphological aspects of a case of carcinoma of the cervix arising from mesonephric duct remnants is presented, and the literature pertaining to these rare tumors is discussed. At the time of initial surgical treatment the tumor was confined to the cervix; however, eventual metastatic dissemination to the bony and soft tissues of the pelvis, the lungs, and the lower vertebral column resulted in the patient's death 8 years later. The tumor appeared refractory to further attempts at treatment with radiation, progestational therapy, and variety of chemotherapeutic agents. The observation of a focal cylindromatous growth pattern, not previously described in tumors of this type, is presented."} {"id": "PMID:172219", "title": "Pleomorphic adenoma of the salivary gland. With special reference to histochemical and electron microscopic studies and biochemical analysis of glycosaminoglycans in vivo and in vitro.", "content": "Pleomorphic adenoma of the salivary gland is classified into two types based on the morphology of the cells and biochemical analysis of glycosaminoglycans. Type 1: the tumors consisted mainly of spindle cells, producing a large amount of mucinous material, and contained not only chondroitin 4- and 6-sulfate and hyaluronic acid but also heparan sulfate. When the tumors of this type were dissociated and cultivated, spindle cells proliferated vigorously as mulitlayer and secreted mucinous substance into the intercellular space. The cells looked like non-epithelial cells in a conventional culture bottle, but showed an epithelial-like arrangement when they were cultivated in sponge matrix or inoculated subcutaneously into mice. Fine fibres stained with orceine or resorcin-fuchsin were observed in the intercellular material both in resected tissue and in culture. Type 2: the tumors consisted mainly of ductal cells, having no mucinous area, and contained little heparan sulfate. When the tumors were cultivated, the growth of epithelial-like polygonal cells was observed in monotonous pattern, producing scanty intercellular substance, and proliferating, as monolayer, much less rapidly than the cells of Type 1.", "contents": "Pleomorphic adenoma of the salivary gland. With special reference to histochemical and electron microscopic studies and biochemical analysis of glycosaminoglycans in vivo and in vitro. Pleomorphic adenoma of the salivary gland is classified into two types based on the morphology of the cells and biochemical analysis of glycosaminoglycans. Type 1: the tumors consisted mainly of spindle cells, producing a large amount of mucinous material, and contained not only chondroitin 4- and 6-sulfate and hyaluronic acid but also heparan sulfate. When the tumors of this type were dissociated and cultivated, spindle cells proliferated vigorously as mulitlayer and secreted mucinous substance into the intercellular space. The cells looked like non-epithelial cells in a conventional culture bottle, but showed an epithelial-like arrangement when they were cultivated in sponge matrix or inoculated subcutaneously into mice. Fine fibres stained with orceine or resorcin-fuchsin were observed in the intercellular material both in resected tissue and in culture. Type 2: the tumors consisted mainly of ductal cells, having no mucinous area, and contained little heparan sulfate. When the tumors were cultivated, the growth of epithelial-like polygonal cells was observed in monotonous pattern, producing scanty intercellular substance, and proliferating, as monolayer, much less rapidly than the cells of Type 1."} {"id": "PMID:172220", "title": "Childhood sarcomas and lymphomas. Characterization of new cell lines and search for type-C virus.", "content": "Four cell lines were derived from childhood malignancies: rhabdomyosarcoma, sarcoma, lymphosarcoma and an American Burkitt's lymphoma. Cells of the four lines formed tumors in immunosuppressed newborn hamsters. The tumors had a microscopic appearance like that of the tumors from which the cell lines were derived. No virus-like particles were detected by electron microscopy in the cell lines after treatment with bromodeoxyuridine; no hamster type-C virus expression was present in cell lines derived from the hamster tumors. Chromosome constitution and in vitro growth properties of the cell lines were studied as was the fibrinolytic function of the sarcoma lines.", "contents": "Childhood sarcomas and lymphomas. Characterization of new cell lines and search for type-C virus. Four cell lines were derived from childhood malignancies: rhabdomyosarcoma, sarcoma, lymphosarcoma and an American Burkitt's lymphoma. Cells of the four lines formed tumors in immunosuppressed newborn hamsters. The tumors had a microscopic appearance like that of the tumors from which the cell lines were derived. No virus-like particles were detected by electron microscopy in the cell lines after treatment with bromodeoxyuridine; no hamster type-C virus expression was present in cell lines derived from the hamster tumors. Chromosome constitution and in vitro growth properties of the cell lines were studied as was the fibrinolytic function of the sarcoma lines."} {"id": "PMID:172222", "title": "Estrogen receptors in hormone-dependent breast cancers.", "content": "The determination of estrogen receptor (estrophilin) in human breast cancers, both primary and metastatic, can furnish information useful to the clinician in his choice of the optimal therapy for the individual patient with advanced disease. Of patients with significant tumor estrophilin levels, most, but not all, will respond favorably to endocrine therapy. Women whose cancers lack sufficient amounts of estrophilin have little or no chance of benefit from endocrine ablation or hormone administration and probably should be treated directly by alternative types of therapy.", "contents": "Estrogen receptors in hormone-dependent breast cancers. The determination of estrogen receptor (estrophilin) in human breast cancers, both primary and metastatic, can furnish information useful to the clinician in his choice of the optimal therapy for the individual patient with advanced disease. Of patients with significant tumor estrophilin levels, most, but not all, will respond favorably to endocrine therapy. Women whose cancers lack sufficient amounts of estrophilin have little or no chance of benefit from endocrine ablation or hormone administration and probably should be treated directly by alternative types of therapy."} {"id": "PMID:172223", "title": "Potential carcinogenicity of food additives and contaminants.", "content": "The potential role in carcinogenesis of food additives and contaminants presents a complex problem in terms of assessing the risk to the general public. Long-term testing in laboratory animals is still the most feasible method for determining potential carcinogenicity of various chemicals. The disadvantages encountered in the present methods of animal testing are discussed and a review is made of the current status of particular food additives and contaminants under scrutiny as possible carcinogens. It is suggested that, since it may not be possible to remove all carcinogenic materials from the environment, methods to mitigate or neutralize their harmful effects should be sought. Greater cooperation is called for among food technologists, toxicologists, laboratory researchers, and epidemiologists in the decision-making process regarding the role of possibly carcinogenic additives and contaminants.", "contents": "Potential carcinogenicity of food additives and contaminants. The potential role in carcinogenesis of food additives and contaminants presents a complex problem in terms of assessing the risk to the general public. Long-term testing in laboratory animals is still the most feasible method for determining potential carcinogenicity of various chemicals. The disadvantages encountered in the present methods of animal testing are discussed and a review is made of the current status of particular food additives and contaminants under scrutiny as possible carcinogens. It is suggested that, since it may not be possible to remove all carcinogenic materials from the environment, methods to mitigate or neutralize their harmful effects should be sought. Greater cooperation is called for among food technologists, toxicologists, laboratory researchers, and epidemiologists in the decision-making process regarding the role of possibly carcinogenic additives and contaminants."} {"id": "PMID:172224", "title": "Inhibition of replication of virus-transformed fibroblasts by antibodies to RNA.", "content": "The activity of 7S immunoglobulins (Ig) antibody to RNA, obtained in rabbits after a prolonged immunization with RNA-methylated bovine serum albumin complex was evaluated in vitro on normal (3T3) and simian virus 40-transformed (SV 3T3) mouse fibroblasts. The presence of anti-RNA antibody in the culture medium inhibited both the SV 3T3 cell proliferation and the [3H]thymidine incorporation. In contrast, an increased [3H]uridine incorporation was evident within 48 and 96 hr of culture. No significant modification in these 3 parameters was observed in 3T3 cultures treated in the same manner. Both 3T3 and SV 3T3 showed cytoplasmic fluorescence when cultured in the presence of fluoresceinated anti-RNA Ig. However, with the indirect fluorescence technique anti-RNA Ig were detected in SV 3T3 cytoplasm only. These data suggest that anti-RNA Ig were taken up by both 3T3 and SV 3T3, but only in SV 3T3 did the anti-RNA Ig retain their antigenic properties and block cellular proliferation.", "contents": "Inhibition of replication of virus-transformed fibroblasts by antibodies to RNA. The activity of 7S immunoglobulins (Ig) antibody to RNA, obtained in rabbits after a prolonged immunization with RNA-methylated bovine serum albumin complex was evaluated in vitro on normal (3T3) and simian virus 40-transformed (SV 3T3) mouse fibroblasts. The presence of anti-RNA antibody in the culture medium inhibited both the SV 3T3 cell proliferation and the [3H]thymidine incorporation. In contrast, an increased [3H]uridine incorporation was evident within 48 and 96 hr of culture. No significant modification in these 3 parameters was observed in 3T3 cultures treated in the same manner. Both 3T3 and SV 3T3 showed cytoplasmic fluorescence when cultured in the presence of fluoresceinated anti-RNA Ig. However, with the indirect fluorescence technique anti-RNA Ig were detected in SV 3T3 cytoplasm only. These data suggest that anti-RNA Ig were taken up by both 3T3 and SV 3T3, but only in SV 3T3 did the anti-RNA Ig retain their antigenic properties and block cellular proliferation."} {"id": "PMID:172225", "title": "Cultivation of medulloblastoma cells derived from simian adenovirus SA7-induced hamster brain tumor.", "content": "In vitro cultivation of medulloblastoma cells was successfully established from hamster brain tumors induced by simian adenovirus SA7. These tumor cells possess morphological features in cultures that are very similar to those of the original tumor. Both tubular and rosette growth patterns were evident. At the ultrastructural level only small numbers of cytoplasmic organelles could be detected in the tumor cells, typical of generally immature and/or undifferentiated cells. The proliferation of these tumor cells depended upon properly dense initial platings. In addition, it was found that single medulloblastoma cells could be stimulated to produce colonies if treated for 10 days with conditioned medium. Inoculation of these cells into synergenic animals resulted in 100% uptake. Survival of the hamsters was directly correlated with the number of cells injected. This new medulloblastoma cell line may prove to be a useful model for experimental brain tumor studies.", "contents": "Cultivation of medulloblastoma cells derived from simian adenovirus SA7-induced hamster brain tumor. In vitro cultivation of medulloblastoma cells was successfully established from hamster brain tumors induced by simian adenovirus SA7. These tumor cells possess morphological features in cultures that are very similar to those of the original tumor. Both tubular and rosette growth patterns were evident. At the ultrastructural level only small numbers of cytoplasmic organelles could be detected in the tumor cells, typical of generally immature and/or undifferentiated cells. The proliferation of these tumor cells depended upon properly dense initial platings. In addition, it was found that single medulloblastoma cells could be stimulated to produce colonies if treated for 10 days with conditioned medium. Inoculation of these cells into synergenic animals resulted in 100% uptake. Survival of the hamsters was directly correlated with the number of cells injected. This new medulloblastoma cell line may prove to be a useful model for experimental brain tumor studies."} {"id": "PMID:172226", "title": "Inhibition by methioninyl adenylate of focus formation by Rous sarcoma virus.", "content": "Methioninyl adenylate is a specific and potent inhibitor of the enzyme methionyl-tRNA synthetase and, consequently, of protein biosynthesis. In cultures of chick embryo fibroblasts infected with Rous sarcoma virus, incubation for a 2-day period with 1 to 3 mM concentrations of this inhibitor, as late as 4 days after infection, irreversibly prevented subsequent formation of foci of transformed cells. Later addition could also elicit the irreversible disappearance of already existing foci, by phenotypic reversion and/or cell killing. Virus production in transformed cells and replication in newly infected cells were also inhibited but to a lesser degree. Under the same conditions, the same concentrations of methioninyl adenylate caused only a reversible growth arrest of normal cells. The selective toxicity of the inhibitor for transformed cells is not due to a greater affinity for the target enzyme, but it may be due to the fact that inhibition of protein biosynthesis is only partially reversible in these cells, whereas it is fully reversible in normal cells.", "contents": "Inhibition by methioninyl adenylate of focus formation by Rous sarcoma virus. Methioninyl adenylate is a specific and potent inhibitor of the enzyme methionyl-tRNA synthetase and, consequently, of protein biosynthesis. In cultures of chick embryo fibroblasts infected with Rous sarcoma virus, incubation for a 2-day period with 1 to 3 mM concentrations of this inhibitor, as late as 4 days after infection, irreversibly prevented subsequent formation of foci of transformed cells. Later addition could also elicit the irreversible disappearance of already existing foci, by phenotypic reversion and/or cell killing. Virus production in transformed cells and replication in newly infected cells were also inhibited but to a lesser degree. Under the same conditions, the same concentrations of methioninyl adenylate caused only a reversible growth arrest of normal cells. The selective toxicity of the inhibitor for transformed cells is not due to a greater affinity for the target enzyme, but it may be due to the fact that inhibition of protein biosynthesis is only partially reversible in these cells, whereas it is fully reversible in normal cells."} {"id": "PMID:172227", "title": "Focal infection and transformation in situ of thymus cell subclasses by a thymotropic murine leukemia virus.", "content": "Studies on the maturational lineages of thymic lymphocytes have revealed several subclasses which are distinguishable on the basis of cell size, topographic distribution within the thymus, DNA synthetic and mitotic activity, migratory behavior, and other properties. Strain C57BL/Ka mice were inoculated with radiation leukemia virus at different concentrations, and tissues were removed at defined intervals. Sequential sections were analyzed for virus-specific cytoplasmic antigen expression, for morphological evidence of neoplastic transformation, and for alkaline phosphatase activity. The first detectable sign of MuLV infection was the focal appearance of cytoplasmic viral antigens in cells of the outer thymic cortex, followed by coalescence of such foci and, several weeks later, by the appearance of morphologically transformed and alkaline phosphatase-positive cells, again often focally distributed in the outer thymic cortex. These observations strongly suggest that the large, mitotically active cells of the outer thymic cortex are the principal source of target cells for both productive infection and subsequent lymphoma induction by the virus.", "contents": "Focal infection and transformation in situ of thymus cell subclasses by a thymotropic murine leukemia virus. Studies on the maturational lineages of thymic lymphocytes have revealed several subclasses which are distinguishable on the basis of cell size, topographic distribution within the thymus, DNA synthetic and mitotic activity, migratory behavior, and other properties. Strain C57BL/Ka mice were inoculated with radiation leukemia virus at different concentrations, and tissues were removed at defined intervals. Sequential sections were analyzed for virus-specific cytoplasmic antigen expression, for morphological evidence of neoplastic transformation, and for alkaline phosphatase activity. The first detectable sign of MuLV infection was the focal appearance of cytoplasmic viral antigens in cells of the outer thymic cortex, followed by coalescence of such foci and, several weeks later, by the appearance of morphologically transformed and alkaline phosphatase-positive cells, again often focally distributed in the outer thymic cortex. These observations strongly suggest that the large, mitotically active cells of the outer thymic cortex are the principal source of target cells for both productive infection and subsequent lymphoma induction by the virus."} {"id": "PMID:172228", "title": "RNA sulfurtransferase activity in rat liver and chemically induced hepatomas.", "content": "RNA sulfurtransferase activity has been detected in rat liver and in hepatomas from rats fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene for 14 to 18 weeks. The reaction measured was the transfer of sulfur from cysteine to acceptor sites in Escherichia coli B transfer RNA (tRNA). Specific activities of the enzymes in liver and hepatoma supernatant fractions were similar, as were the rates and extents of sulfur transfer to tRNA. DEAE-cellulose chromatography of digests of the [35S]tRNA reaction products revealed 3 peaks associated with nucleotide material, the amounts of these peaks differing in tRNA from liver and hepatoma systems. This may suggest differences in specific sulfurtransferases in these tissues.", "contents": "RNA sulfurtransferase activity in rat liver and chemically induced hepatomas. RNA sulfurtransferase activity has been detected in rat liver and in hepatomas from rats fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene for 14 to 18 weeks. The reaction measured was the transfer of sulfur from cysteine to acceptor sites in Escherichia coli B transfer RNA (tRNA). Specific activities of the enzymes in liver and hepatoma supernatant fractions were similar, as were the rates and extents of sulfur transfer to tRNA. DEAE-cellulose chromatography of digests of the [35S]tRNA reaction products revealed 3 peaks associated with nucleotide material, the amounts of these peaks differing in tRNA from liver and hepatoma systems. This may suggest differences in specific sulfurtransferases in these tissues."} {"id": "PMID:172229", "title": "Polyamine metabolism in normal and in virus-transformed chick embryo fibroblasts.", "content": "The effect of transformation by Rous sarcoma virus on the ornithine decarboxylase levels of chick embryo fibroblasts was studied. Infection with Rous sarcoma virus resulted in increased ornithine decarboxylase activity which preceded morphological alterations by at least 24 hr. The ornithine decarboxylase levels of normal controls, unlike those in Rous sarcoma virus-infected cells, declined with age, so that the enzyme activity of transformed cells was increased twentyfold 5 days postinfection. Infection with a temperature-sensitive mutant of Rous sarcoma virus, T5, stimulated ornithine decarboxylase activity of chick embryo fibroblasts at the permissive (37 degrees) but not at the nonpermissive (42 degrees) temperature. The ornithine decarboxylase activity of T5-infected cells shifted from 42 degrees to 37 degrees increased within 2 hr and reached the levels of wild-type, Schmidt-Ruppin-17A-transformed cells in 11 hr. When T5-transformed fibroblasts were shifted to the nonpermissive temperature, ornithine decarboxylase activity decreased fivefold within 4 hr and paralleled the levels of normal controls in 11 hr. Shifting of temperatures of incubation caused comparable alterations in cellular putrescine but not in spermine or spermidine content.", "contents": "Polyamine metabolism in normal and in virus-transformed chick embryo fibroblasts. The effect of transformation by Rous sarcoma virus on the ornithine decarboxylase levels of chick embryo fibroblasts was studied. Infection with Rous sarcoma virus resulted in increased ornithine decarboxylase activity which preceded morphological alterations by at least 24 hr. The ornithine decarboxylase levels of normal controls, unlike those in Rous sarcoma virus-infected cells, declined with age, so that the enzyme activity of transformed cells was increased twentyfold 5 days postinfection. Infection with a temperature-sensitive mutant of Rous sarcoma virus, T5, stimulated ornithine decarboxylase activity of chick embryo fibroblasts at the permissive (37 degrees) but not at the nonpermissive (42 degrees) temperature. The ornithine decarboxylase activity of T5-infected cells shifted from 42 degrees to 37 degrees increased within 2 hr and reached the levels of wild-type, Schmidt-Ruppin-17A-transformed cells in 11 hr. When T5-transformed fibroblasts were shifted to the nonpermissive temperature, ornithine decarboxylase activity decreased fivefold within 4 hr and paralleled the levels of normal controls in 11 hr. Shifting of temperatures of incubation caused comparable alterations in cellular putrescine but not in spermine or spermidine content."} {"id": "PMID:172230", "title": "Functional properties of mitochondria isolated from murine L5178 lymphoblasts grown in cell culture.", "content": "Mitochondria were isolated from lymphoblasts grown for 5 days in cell culture. Measurement of mitochondrial respiratory activity revealed poor response to adenosine 5'-diphosphate with reduced nicotinamide adenine dinucleotide-linked substrates but well-coupled active respiration with succinate as substrate. These mitochondria also exhibited rapid initial rates of respiration-supported calcium uptake as measured by dual-beam spectrophotometry. H+/2e- and Ca2+/2e- ratios were in normal limits for the lymphoblast mitochondria during calcium uptake in the presence of phosphate. In the absence of phosphate no calcium uptake, H+ ejection, or stimulation of oxygen consumption was observed. However, the lack of discharge of the accumulated calcium from the lymphoblast mitochondria upon inhibition of respiration suggests possible different mechanisms of cation transport compared to mitochondria from normal, mammalian cell types. Electron microscopy of freshly prepared mitochondrial suspensions revealed preparations with intact outer membranes and abundant cristae and that were relatively free of other cellular structures. These studies demonstrate the feasibility of obtaining intact respiring mitochondria from cultured lymphoid cells and indicate that active ion transport in these mitochondria may be significantly different from \"normal\" cell mitochondria.", "contents": "Functional properties of mitochondria isolated from murine L5178 lymphoblasts grown in cell culture. Mitochondria were isolated from lymphoblasts grown for 5 days in cell culture. Measurement of mitochondrial respiratory activity revealed poor response to adenosine 5'-diphosphate with reduced nicotinamide adenine dinucleotide-linked substrates but well-coupled active respiration with succinate as substrate. These mitochondria also exhibited rapid initial rates of respiration-supported calcium uptake as measured by dual-beam spectrophotometry. H+/2e- and Ca2+/2e- ratios were in normal limits for the lymphoblast mitochondria during calcium uptake in the presence of phosphate. In the absence of phosphate no calcium uptake, H+ ejection, or stimulation of oxygen consumption was observed. However, the lack of discharge of the accumulated calcium from the lymphoblast mitochondria upon inhibition of respiration suggests possible different mechanisms of cation transport compared to mitochondria from normal, mammalian cell types. Electron microscopy of freshly prepared mitochondrial suspensions revealed preparations with intact outer membranes and abundant cristae and that were relatively free of other cellular structures. These studies demonstrate the feasibility of obtaining intact respiring mitochondria from cultured lymphoid cells and indicate that active ion transport in these mitochondria may be significantly different from \"normal\" cell mitochondria."} {"id": "PMID:172231", "title": "Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo.", "content": "Formycin B inhibited growth of L5178Y mouse leukemia cells in concentrations of less than twice the concentration that inhibits cell proliferation at 50% by cytostasis; at higher concentrations (more than twice the 50% concentration mentioned), the cells were killed. In cells treated with the concentration that inhibits cell proliferation at 50%, the average cell volume did not change. The formycin B inhibitory effect on cell proliferation was reduced by coincubation with nicotinamide adenine diphosphate or adenosine. The biosyntheses of DNA,RNA, and protein in whole cells were sensitively inhibited by formycin B as checked by incorporation studies with radioactive precursors. In addition, the formation of polyadenosine diphosphoribose was reduced even with higher sensitivity; in particular the extent of adenosine diphosphate ribosylation of histone subfraction H1 was reduced. Formycin B has been shown to be an inhibitor for the polyadenosine diphosphoribose polymerase, isolated from oviduct nuclei of quails. Both the chromatin-bound and the soluble enzyme are inhibited competitively; the relative affinity (Ki/Km) of formycin B to the polyadenosine diphosphoribose polymerase is 1.5.", "contents": "Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo. Formycin B inhibited growth of L5178Y mouse leukemia cells in concentrations of less than twice the concentration that inhibits cell proliferation at 50% by cytostasis; at higher concentrations (more than twice the 50% concentration mentioned), the cells were killed. In cells treated with the concentration that inhibits cell proliferation at 50%, the average cell volume did not change. The formycin B inhibitory effect on cell proliferation was reduced by coincubation with nicotinamide adenine diphosphate or adenosine. The biosyntheses of DNA,RNA, and protein in whole cells were sensitively inhibited by formycin B as checked by incorporation studies with radioactive precursors. In addition, the formation of polyadenosine diphosphoribose was reduced even with higher sensitivity; in particular the extent of adenosine diphosphate ribosylation of histone subfraction H1 was reduced. Formycin B has been shown to be an inhibitor for the polyadenosine diphosphoribose polymerase, isolated from oviduct nuclei of quails. Both the chromatin-bound and the soluble enzyme are inhibited competitively; the relative affinity (Ki/Km) of formycin B to the polyadenosine diphosphoribose polymerase is 1.5."} {"id": "PMID:172232", "title": "Inhibition of formation of microtubular paracrystals in HeLa-S3 cells by neocarzinostatin.", "content": "The effect of an antitumor antibiotic, neocarzinostatin (NCS), on the formation of microtubular paracrystals (PC) induced by vinblastine sulfate, 10 mug/ml, in HeLa-S3 cells was examined by phase-contrast microscopy. The pretreatment of HeLa-S3 cells with NCS, 5 to 50 mug/ml, for 4 hr prevented the PC formation, and there was a dose response of NCS to the degree of inhibition. When the same inhibitory effect on PC formation was examined with other antitumor agents at high doses (50 mug/ml), colchicine was found to be one of the most effective agents, like NCS. Puromycin, antimycin, adriamycin, cytochalasin B, and cycloheximide revealed moderate activity, and the other antibiotics, such as mitomycin C, bleomycin, and rifampicin, did not show any effect at all. NCS was a unique antibiotic that inhibited PC formation among inhibitors of DNA synthesis. It was suggested that NCS affects the microfibrillar-microtubular proteins system in vivo, resulting in the inhibitions of organization of spindle fibers from microtubules at the G2 phase in HeLa cells.", "contents": "Inhibition of formation of microtubular paracrystals in HeLa-S3 cells by neocarzinostatin. The effect of an antitumor antibiotic, neocarzinostatin (NCS), on the formation of microtubular paracrystals (PC) induced by vinblastine sulfate, 10 mug/ml, in HeLa-S3 cells was examined by phase-contrast microscopy. The pretreatment of HeLa-S3 cells with NCS, 5 to 50 mug/ml, for 4 hr prevented the PC formation, and there was a dose response of NCS to the degree of inhibition. When the same inhibitory effect on PC formation was examined with other antitumor agents at high doses (50 mug/ml), colchicine was found to be one of the most effective agents, like NCS. Puromycin, antimycin, adriamycin, cytochalasin B, and cycloheximide revealed moderate activity, and the other antibiotics, such as mitomycin C, bleomycin, and rifampicin, did not show any effect at all. NCS was a unique antibiotic that inhibited PC formation among inhibitors of DNA synthesis. It was suggested that NCS affects the microfibrillar-microtubular proteins system in vivo, resulting in the inhibitions of organization of spindle fibers from microtubules at the G2 phase in HeLa cells."} {"id": "PMID:172233", "title": "The enzymatic basis of the selective action of cyclophosphamide.", "content": "The initial metabolic products of cyclophosphamide (4-hydroxy-cyclophosphamide and aldophosphamide) were prepared biologically in unpurified form. Their toxicity to tumor cells were tested by bioassay techniques and in cell culture, and the deactivation abilities of various tissue-soluble fractions were quantitated. Liver and kidney cytosol effectively deactivated the primary metabolites, whereas cytosols from gastrointestinal tract mucosa, Walker ascites tumor, and spleen were less efficient. When [14C]cyclophosphamide was activated and incubated with liver cytosol, 34% of all radioactivity was identified as carboxyphosphamide, by mass spectrometry of the methyl ester. Measurement of alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) activities by reduced nicotinamide adenine dinucleotide production revealed a qualitative correspondence between aldehyde dehydrogenase activity and deactivation ability. Unpurified aldophosphamide and the analogs prepared from 6-methyl- and 5,5-dimethylcyclophosphamides were substrates for nicotinamide adenine dinucleotide-requiring enzymes, whereas incubation of 4-hydroxy-4-methylcyclophosphamide in an unfractionated incubation mixture with liver soluble enzymes did not cause reduced nicotinamide adenine dinucleotide production.", "contents": "The enzymatic basis of the selective action of cyclophosphamide. The initial metabolic products of cyclophosphamide (4-hydroxy-cyclophosphamide and aldophosphamide) were prepared biologically in unpurified form. Their toxicity to tumor cells were tested by bioassay techniques and in cell culture, and the deactivation abilities of various tissue-soluble fractions were quantitated. Liver and kidney cytosol effectively deactivated the primary metabolites, whereas cytosols from gastrointestinal tract mucosa, Walker ascites tumor, and spleen were less efficient. When [14C]cyclophosphamide was activated and incubated with liver cytosol, 34% of all radioactivity was identified as carboxyphosphamide, by mass spectrometry of the methyl ester. Measurement of alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) activities by reduced nicotinamide adenine dinucleotide production revealed a qualitative correspondence between aldehyde dehydrogenase activity and deactivation ability. Unpurified aldophosphamide and the analogs prepared from 6-methyl- and 5,5-dimethylcyclophosphamides were substrates for nicotinamide adenine dinucleotide-requiring enzymes, whereas incubation of 4-hydroxy-4-methylcyclophosphamide in an unfractionated incubation mixture with liver soluble enzymes did not cause reduced nicotinamide adenine dinucleotide production."} {"id": "PMID:172234", "title": "RNA type C virus antigens in hamster cells transformed by carcinogenic DNA viruses and chemicals.", "content": "The passive hemagglutination inhibition technique was used to test serologically for the presence of Syrian hamster type C virus antigen(s) (SHCVA) in a wide variety of normal and transformed hamster cells and tissues. SHCVA could not be detected in normal tissues or nonneoplastic tissues of tumor-bearing Syrian hamsters. Normal hamster embryo cells or cells transformed in vitro by simian adenovirus, by chemical alone, or doubly transformed by simian adenovirus and chemical did not contain SHCVA; however, SHCVA was found in a majority of tumors resulting from transplantation of these in vitro-transformed cells. No consistent pattern was observed in the capacity of individual transformed cell lines to produce SHCVA-positive or -negative tumors. When cells of a given transformed line were inoculated at 4 sites on each of 8 hamsters, SHCVA-positive tumors were found not to be randomly distributed but rather to be clustered on a few animals. SHCVA could be detected in only a few primary tumors induced by inoculation of carcinogenic DNA viruses; however, both the incidence and titer of SHCVA were significantly increased in a variety of transplanted tumors. These data suggest that SHCVA may be introduced into transplanted, transformed hamster cell tumors during passage in the host animal. Alternatively, in vivo conditions may allow expression of viral antigens not found under in vitro conditions; however, if this is true, only certain animals appear to be capable of activating SHCVA.", "contents": "RNA type C virus antigens in hamster cells transformed by carcinogenic DNA viruses and chemicals. The passive hemagglutination inhibition technique was used to test serologically for the presence of Syrian hamster type C virus antigen(s) (SHCVA) in a wide variety of normal and transformed hamster cells and tissues. SHCVA could not be detected in normal tissues or nonneoplastic tissues of tumor-bearing Syrian hamsters. Normal hamster embryo cells or cells transformed in vitro by simian adenovirus, by chemical alone, or doubly transformed by simian adenovirus and chemical did not contain SHCVA; however, SHCVA was found in a majority of tumors resulting from transplantation of these in vitro-transformed cells. No consistent pattern was observed in the capacity of individual transformed cell lines to produce SHCVA-positive or -negative tumors. When cells of a given transformed line were inoculated at 4 sites on each of 8 hamsters, SHCVA-positive tumors were found not to be randomly distributed but rather to be clustered on a few animals. SHCVA could be detected in only a few primary tumors induced by inoculation of carcinogenic DNA viruses; however, both the incidence and titer of SHCVA were significantly increased in a variety of transplanted tumors. These data suggest that SHCVA may be introduced into transplanted, transformed hamster cell tumors during passage in the host animal. Alternatively, in vivo conditions may allow expression of viral antigens not found under in vitro conditions; however, if this is true, only certain animals appear to be capable of activating SHCVA."} {"id": "PMID:172235", "title": "Binding of the azocarcinogen 3'-methyl-p-dimethylaminoazobenzene to cellular components of normal rat liver and azocarcinogen-induced hepatomas.", "content": "The location of binding sites for 3'-methyl-p-dimethylaminoazobenzene (3'-Me-DAB) or metabolites on components of rat liver cells and hepatoma cells in tumors induced by this carcinogen was determined at 2 stages during the induction of tumors in rats: (a) in normal liver immediately following the application of a massive dose of the azocarcinogen by intragastric feeding, and (b) in liver and tumor after hepatomas had developed following repeated exposures to the carcinogen by s.c. injections. Bound 3'-Me-DAB or metabolites were detected by the use of rabbit antisera directed against either p-azoazobenzene or p'-azo-p-dimethylaminoazobenzene in an indirect fluorescent antibody technique. Soon after massive intragastric doses of 3'-Me-DAB, the staining observed when the anti-p-azoazobenzene antiserum was used was principally on cytoplasmic components of liver cells with some staining of the intranuclear components. When the second antiserum, anti-p'-azo-p-dimethylaminoazobenzene antiserum, was used, the most intense fluorescent staining was on the nuclear membranes, although there was some cytoplasmic and intranuclear staining as well.", "contents": "Binding of the azocarcinogen 3'-methyl-p-dimethylaminoazobenzene to cellular components of normal rat liver and azocarcinogen-induced hepatomas. The location of binding sites for 3'-methyl-p-dimethylaminoazobenzene (3'-Me-DAB) or metabolites on components of rat liver cells and hepatoma cells in tumors induced by this carcinogen was determined at 2 stages during the induction of tumors in rats: (a) in normal liver immediately following the application of a massive dose of the azocarcinogen by intragastric feeding, and (b) in liver and tumor after hepatomas had developed following repeated exposures to the carcinogen by s.c. injections. Bound 3'-Me-DAB or metabolites were detected by the use of rabbit antisera directed against either p-azoazobenzene or p'-azo-p-dimethylaminoazobenzene in an indirect fluorescent antibody technique. Soon after massive intragastric doses of 3'-Me-DAB, the staining observed when the anti-p-azoazobenzene antiserum was used was principally on cytoplasmic components of liver cells with some staining of the intranuclear components. When the second antiserum, anti-p'-azo-p-dimethylaminoazobenzene antiserum, was used, the most intense fluorescent staining was on the nuclear membranes, although there was some cytoplasmic and intranuclear staining as well."} {"id": "PMID:172238", "title": "Short-term effects of ACTH on protein synthesis in adrenal cortex cells of young rats.", "content": "Two units of ACTH were administered intraperitoneally to young 20 gm-rats which received an intravenous injection of L-leucine-3H thirteen min later. ACTH-injected rats, and control rats which received the isotope alone, were killed at 2-, 10-, 30- and 60-min intervals. Electron microscope autoradiographs in control animals showed strong amino-acid uptake at pulse time (2-min) in the cytoplasm of adrenal zona fasciculata cells. Label was shared between the endoplasmic reticulum (ER) and mitochondria, and a lower but still considerable uptake was seen in nucleoli. At first chase time interval (10-min) cytoplasmic labelling declined, while nuclear and nucleolar labelling increased, both changing little thereafter, and there was a 10-30 min Golgi peak. ACTH administration provoked an overall increase in amino-acid incorporation into cytoplasm, nucleus and nucleolus at pulse time, with no changes in the distribution of the reactions among organelles. Intensification of labelling was most evident over nucleoli, the grain density of which was four-times as high as in controls. The short-term increase in ER and mitochondrial protein synthesis observed after ACTH injections was considered to be consistent with the hypothesis that most newly-formed proteins in these cells may be involved in the regulation of steroidogenesis. The marked increase in nucleolar labelling suggested the presence of proteins involved in RNA synthesis.", "contents": "Short-term effects of ACTH on protein synthesis in adrenal cortex cells of young rats. Two units of ACTH were administered intraperitoneally to young 20 gm-rats which received an intravenous injection of L-leucine-3H thirteen min later. ACTH-injected rats, and control rats which received the isotope alone, were killed at 2-, 10-, 30- and 60-min intervals. Electron microscope autoradiographs in control animals showed strong amino-acid uptake at pulse time (2-min) in the cytoplasm of adrenal zona fasciculata cells. Label was shared between the endoplasmic reticulum (ER) and mitochondria, and a lower but still considerable uptake was seen in nucleoli. At first chase time interval (10-min) cytoplasmic labelling declined, while nuclear and nucleolar labelling increased, both changing little thereafter, and there was a 10-30 min Golgi peak. ACTH administration provoked an overall increase in amino-acid incorporation into cytoplasm, nucleus and nucleolus at pulse time, with no changes in the distribution of the reactions among organelles. Intensification of labelling was most evident over nucleoli, the grain density of which was four-times as high as in controls. The short-term increase in ER and mitochondrial protein synthesis observed after ACTH injections was considered to be consistent with the hypothesis that most newly-formed proteins in these cells may be involved in the regulation of steroidogenesis. The marked increase in nucleolar labelling suggested the presence of proteins involved in RNA synthesis."} {"id": "PMID:172239", "title": "Alteration of cytochrome c oxidase activity during spermatogenesis in Carcinus maenas.", "content": "During spermatogenesis in the crab, Carcinus maenas, mitochondria in the developing spermatids degenerate. In close association with mitochondrial fragments in late spermatids, an elaborate lattice-like complex of fused membranes is formed and lies in a position adjacent to the acrosome. Mature sperm possess no mitochondria, but a whorl of membranes is present alongside the acrosome in the diffuse nucleus. To ascertain whether or not cytochrome c oxidase activity is lost as the mitochondria disintegrate, differentiating Carcinus maenas spermatids and mature sperm have been studied cytochemically. Cytochfome c oxidase activity was localised by means of the osmophilic compound 3,3'-diaminobenzidine (DAB). Cytochrome c oxidase activity is confined to the cristae of mitochondria in the testis. As spermatids mature most mitochondria are lost. A few mitochondrial fragments may be caught up within the lamellar complex. While they are recognisalbe as mitochondria they retain cytochrome c oxidase activity. The lamellar complex does not show this enzyme activity. These results therefore suggest that the mature sperm of Carcinus maenas do not contain the enzymes normally incorporated in the mitochondrial membrane, capable of oxidative phosphorylation.", "contents": "Alteration of cytochrome c oxidase activity during spermatogenesis in Carcinus maenas. During spermatogenesis in the crab, Carcinus maenas, mitochondria in the developing spermatids degenerate. In close association with mitochondrial fragments in late spermatids, an elaborate lattice-like complex of fused membranes is formed and lies in a position adjacent to the acrosome. Mature sperm possess no mitochondria, but a whorl of membranes is present alongside the acrosome in the diffuse nucleus. To ascertain whether or not cytochrome c oxidase activity is lost as the mitochondria disintegrate, differentiating Carcinus maenas spermatids and mature sperm have been studied cytochemically. Cytochfome c oxidase activity was localised by means of the osmophilic compound 3,3'-diaminobenzidine (DAB). Cytochrome c oxidase activity is confined to the cristae of mitochondria in the testis. As spermatids mature most mitochondria are lost. A few mitochondrial fragments may be caught up within the lamellar complex. While they are recognisalbe as mitochondria they retain cytochrome c oxidase activity. The lamellar complex does not show this enzyme activity. These results therefore suggest that the mature sperm of Carcinus maenas do not contain the enzymes normally incorporated in the mitochondrial membrane, capable of oxidative phosphorylation."} {"id": "PMID:172243", "title": "Effect of methyl methanesulphonate (MMS) and methylene dimethanesulphonate (MDMS) on the template activity of DNA isolated from MDMS-sensitive and -resistant Yoshida cells.", "content": "Both methylene dimethanesulphonate (MDMS) and methyl methanesulphonate (MMS) cause the template activity of Yoshida cell DNA to decrease in a dose-dependent manner. The MDMS-resistant subline of Yoshida tumour is less sensitive in terms of DNA template activity than the MDMS-sensitive subline towards both agents. Although the difference in sensitivity is not reflected in the survival data after each agent, it does suggest that the DNA from each cell line differs in its capacity to function as an efficient template.", "contents": "Effect of methyl methanesulphonate (MMS) and methylene dimethanesulphonate (MDMS) on the template activity of DNA isolated from MDMS-sensitive and -resistant Yoshida cells. Both methylene dimethanesulphonate (MDMS) and methyl methanesulphonate (MMS) cause the template activity of Yoshida cell DNA to decrease in a dose-dependent manner. The MDMS-resistant subline of Yoshida tumour is less sensitive in terms of DNA template activity than the MDMS-sensitive subline towards both agents. Although the difference in sensitivity is not reflected in the survival data after each agent, it does suggest that the DNA from each cell line differs in its capacity to function as an efficient template."} {"id": "PMID:172244", "title": "The inactivation of bacteriophage R17 by ethylating agents: the lethal lesions.", "content": "The biological inactivation of bacteriophage R17 by ethyl methanesulphonate (EMS) and N-ethyl-N-nitrosourea (ENUA) has been studied. At the mean lethal dose for the first compound 8 moles ethyl are bound/mole RNA and with the nitroso compound 3.5 moles ethyl are bound. Analysis of the amounts of the different ethylated derivatives formed shows that the toxicity of the sulphonate can be accounted for by the formation of 3-ethylcytosine, O6-ethylguanine, 1-ethyladenine and chain breaks produced on the hydrolysis of ethyl phosphotriesters. With the nitroso derivative on the other hand, the sum of chain breaks and of bases alkylated on a position involved in specific hydrogen bonding between base pairs only accounts for 65% of the observed toxicity. The possibility that 3-ethyladenine may constitute a lethal lesion is discussed.", "contents": "The inactivation of bacteriophage R17 by ethylating agents: the lethal lesions. The biological inactivation of bacteriophage R17 by ethyl methanesulphonate (EMS) and N-ethyl-N-nitrosourea (ENUA) has been studied. At the mean lethal dose for the first compound 8 moles ethyl are bound/mole RNA and with the nitroso compound 3.5 moles ethyl are bound. Analysis of the amounts of the different ethylated derivatives formed shows that the toxicity of the sulphonate can be accounted for by the formation of 3-ethylcytosine, O6-ethylguanine, 1-ethyladenine and chain breaks produced on the hydrolysis of ethyl phosphotriesters. With the nitroso derivative on the other hand, the sum of chain breaks and of bases alkylated on a position involved in specific hydrogen bonding between base pairs only accounts for 65% of the observed toxicity. The possibility that 3-ethyladenine may constitute a lethal lesion is discussed."} {"id": "PMID:172245", "title": "Assays for phosphotriester formation in the reaction of bacteriophage R17 with a group of alkylating agents.", "content": "The interaction of bacteriophage R17 with 8 compounds has been studied, comparing the contribution of degradation of ribonucleic acid to the total toxicity. Breaks in the RNA chain result from the hydrolysis of phosphotriesters and thus are a measure of the extent of O-alkylation and of the SN1-type mechanism of the reaction. With many alkylating agents mutagenicity and carcinogenicity increase with increasing SN1 character of the reaction. In experiments with methyl methanesulphonate no evidence of degradation was observed at up to 19 times the mean lethal dose (620 methylations/RNA molecule). Breaks in the RNA chain accounted for 1 in 10 of the lethal lesions with beta-hydroxyethyl methanesulphonate, 1 in 60 with bis-(2-chloromethyl)methylamine (nitrogen mustard, HN2), less than 1 in 125 with 2,2-dichlorvinyl dimethyl phosphate (dichlorovos, DDVP), and 1 in 200 with propylene oxide. The hydrolysis rate of bis-(2 chloroethyl)ether was too slow for any reaction to be detected. In reactions with the carcinogen bis-(2-chloromethyl)ether the toxicity observed could be accounted for by the formaldehyde produced on hydrolysis. Cross-linking of the bacteriophage components by formaldehyde reduced the survival range over which the physical state of the RNA could be studied. No evidence of RNA degradation was observed. Reaction of the formaldehyde led to a progressive loss of biological activity over 24 h, a loss which was partially reversed by dialysis.", "contents": "Assays for phosphotriester formation in the reaction of bacteriophage R17 with a group of alkylating agents. The interaction of bacteriophage R17 with 8 compounds has been studied, comparing the contribution of degradation of ribonucleic acid to the total toxicity. Breaks in the RNA chain result from the hydrolysis of phosphotriesters and thus are a measure of the extent of O-alkylation and of the SN1-type mechanism of the reaction. With many alkylating agents mutagenicity and carcinogenicity increase with increasing SN1 character of the reaction. In experiments with methyl methanesulphonate no evidence of degradation was observed at up to 19 times the mean lethal dose (620 methylations/RNA molecule). Breaks in the RNA chain accounted for 1 in 10 of the lethal lesions with beta-hydroxyethyl methanesulphonate, 1 in 60 with bis-(2-chloromethyl)methylamine (nitrogen mustard, HN2), less than 1 in 125 with 2,2-dichlorvinyl dimethyl phosphate (dichlorovos, DDVP), and 1 in 200 with propylene oxide. The hydrolysis rate of bis-(2 chloroethyl)ether was too slow for any reaction to be detected. In reactions with the carcinogen bis-(2-chloromethyl)ether the toxicity observed could be accounted for by the formaldehyde produced on hydrolysis. Cross-linking of the bacteriophage components by formaldehyde reduced the survival range over which the physical state of the RNA could be studied. No evidence of RNA degradation was observed. Reaction of the formaldehyde led to a progressive loss of biological activity over 24 h, a loss which was partially reversed by dialysis."} {"id": "PMID:172247", "title": "[Immunofluorencence localization of secretions related to gonadotropic, corticotropic, melanotropic and somatotropic hormones in hypophysis of Nectophrynoides occidentalis].", "content": "In Nectophryno\u00efdes occidentalis, ovine anti-LH anti beta (1-24) corticotropin, both anti alpha and anti beta MSH and bovine anti-STH antisera allowed us to identify by immunofluorescence gonadotropic, corticotropic, melanotropic and somatotropic hypophysial cells of a viviparous toad. The identification of these different cell types was confirmed by applying a classical cytologic technique to the same sections.", "contents": "[Immunofluorencence localization of secretions related to gonadotropic, corticotropic, melanotropic and somatotropic hormones in hypophysis of Nectophrynoides occidentalis]. In Nectophryno\u00efdes occidentalis, ovine anti-LH anti beta (1-24) corticotropin, both anti alpha and anti beta MSH and bovine anti-STH antisera allowed us to identify by immunofluorescence gonadotropic, corticotropic, melanotropic and somatotropic hypophysial cells of a viviparous toad. The identification of these different cell types was confirmed by applying a classical cytologic technique to the same sections."} {"id": "PMID:172248", "title": "[Identification of cAMP dependant protein kinases in human lymphocytes].", "content": "Chromatographic purification by \"DEAE\" cellulose resolves the cAMP binding proteins in human lymphocytes into three parts. In presence of Mg++ each one possesses cAMP dependent protein-kinase activity, one of them showing allosteric characteristics.", "contents": "[Identification of cAMP dependant protein kinases in human lymphocytes]. Chromatographic purification by \"DEAE\" cellulose resolves the cAMP binding proteins in human lymphocytes into three parts. In presence of Mg++ each one possesses cAMP dependent protein-kinase activity, one of them showing allosteric characteristics."} {"id": "PMID:172249", "title": "[Demonstration of antigen-antibody complex of TSV5C12 cell membranes by means of guinea pig fluorescent anti-complement antibodies].", "content": "The application of rabbit anti-guinea pig complement fluorescent antibody to SV40 transformed cells demonstrated the presence of immune complexes on the cell membrane surface. The presence of such complexes was not detectable by using fluorescent rabbit anti-hamster immunoglobulins antisera.", "contents": "[Demonstration of antigen-antibody complex of TSV5C12 cell membranes by means of guinea pig fluorescent anti-complement antibodies]. The application of rabbit anti-guinea pig complement fluorescent antibody to SV40 transformed cells demonstrated the presence of immune complexes on the cell membrane surface. The presence of such complexes was not detectable by using fluorescent rabbit anti-hamster immunoglobulins antisera."} {"id": "PMID:172250", "title": "[Resistance to association of antibiotics (polymyxin and penicillin) in relation to cell concentration of two bacterial species in the same inoculum. Complementary inoculum effect].", "content": "Dense suspensions of Sa. typhi (Polys Penr) and of St. aureus (Polyr Pens) proliferate on gelose medium added with the two antibiotics only if the inoculum is mixed. The growth is probably due to the partial neutralization of the antibiotics following the formation of complexes between these antibiotics and some constituents of the two strains.", "contents": "[Resistance to association of antibiotics (polymyxin and penicillin) in relation to cell concentration of two bacterial species in the same inoculum. Complementary inoculum effect]. Dense suspensions of Sa. typhi (Polys Penr) and of St. aureus (Polyr Pens) proliferate on gelose medium added with the two antibiotics only if the inoculum is mixed. The growth is probably due to the partial neutralization of the antibiotics following the formation of complexes between these antibiotics and some constituents of the two strains."} {"id": "PMID:172251", "title": "[RNA fragments rich in G and A nucleotides obligatory for in vitro DNA replication of phages phi-X 174 and lambda].", "content": "Evidence was presented that in vitro conversion of single-stranded DNA of phage phi X 174 to the double-stranded replicative form by partially purified DNA-dependent DNA polymerase I requires a specific RNA fragment acting as primer (25-50 nucleotides). RNA fragments highly rich in nucleotides A and G were obtained by partial degradation of E. coli M 500 Sho-R ribosomal RNA with pancreatic ribonuclease. They become covalently bound to the newly synthesized DNA chain of the replicative form of phage phi X 174. These RNA fragments are also required for in vitro replication of lambda phage DNA.", "contents": "[RNA fragments rich in G and A nucleotides obligatory for in vitro DNA replication of phages phi-X 174 and lambda]. Evidence was presented that in vitro conversion of single-stranded DNA of phage phi X 174 to the double-stranded replicative form by partially purified DNA-dependent DNA polymerase I requires a specific RNA fragment acting as primer (25-50 nucleotides). RNA fragments highly rich in nucleotides A and G were obtained by partial degradation of E. coli M 500 Sho-R ribosomal RNA with pancreatic ribonuclease. They become covalently bound to the newly synthesized DNA chain of the replicative form of phage phi X 174. These RNA fragments are also required for in vitro replication of lambda phage DNA."} {"id": "PMID:172252", "title": "[Correlation between agglutinability of concanavalin A and nucleic acid synthesis induced by polyoma virus].", "content": "We have previously shown the induction of agglutinability by concanavalin A by abortice infection of BHK 21 cells with polyoma virus. In this system, the maximal agglutination occurred simultaneously with the first mitosis. Using inhibitors of macromolecule synthesis in an amitotic system, we showed that this agglutinability was correlated with cell DNA synthesis.", "contents": "[Correlation between agglutinability of concanavalin A and nucleic acid synthesis induced by polyoma virus]. We have previously shown the induction of agglutinability by concanavalin A by abortice infection of BHK 21 cells with polyoma virus. In this system, the maximal agglutination occurred simultaneously with the first mitosis. Using inhibitors of macromolecule synthesis in an amitotic system, we showed that this agglutinability was correlated with cell DNA synthesis."} {"id": "PMID:172253", "title": "[Electron microscopic study of the penetration and distribution of somitic cells in the mesoblast of the limb buds of reptiles (Anguis fragilis and Lacerta viridis)].", "content": "Based on characteristics of mitochondria and on the amount of lipid inclusions, a distinction between somitic cells and mesoblastic somatopleural cells is possible, at the early stages of the development of the limb bud in Reptiles (Anguis fragilis and Lacerta viridis). The dislocation of the ventral processes of the somites and the localisation of the somitic cells in the mesoblast of the anterior limb buds could be studied.", "contents": "[Electron microscopic study of the penetration and distribution of somitic cells in the mesoblast of the limb buds of reptiles (Anguis fragilis and Lacerta viridis)]. Based on characteristics of mitochondria and on the amount of lipid inclusions, a distinction between somitic cells and mesoblastic somatopleural cells is possible, at the early stages of the development of the limb bud in Reptiles (Anguis fragilis and Lacerta viridis). The dislocation of the ventral processes of the somites and the localisation of the somitic cells in the mesoblast of the anterior limb buds could be studied."} {"id": "PMID:172254", "title": "[Effect of antioxidant substances on the level of free organic radicals naturally present in the rat diaphragm].", "content": "Using the electron spin resonance method, the effect of antioxydants on the number of natural organic free radicals is studied in the case of the diaphragm of the Rat. The effect observed shows an important decrease in the free radical concentration, which may, in the case of ascorbic acid and BHT, lead to their complete disappearance. These results are discussed in the light of the hypothesis according to which antioxydants play a role in the lengthening of the life span because of their fundamental character of inhibitors of free radicals.", "contents": "[Effect of antioxidant substances on the level of free organic radicals naturally present in the rat diaphragm]. Using the electron spin resonance method, the effect of antioxydants on the number of natural organic free radicals is studied in the case of the diaphragm of the Rat. The effect observed shows an important decrease in the free radical concentration, which may, in the case of ascorbic acid and BHT, lead to their complete disappearance. These results are discussed in the light of the hypothesis according to which antioxydants play a role in the lengthening of the life span because of their fundamental character of inhibitors of free radicals."} {"id": "PMID:172255", "title": "[Activity of specific collagenases in developing granulomatous tissues].", "content": "Specific collagenases are activated rapidly in inflamed tissues. This activity reaches a higher level in acute inflammation than in chronic inflammation. It appears to be related to an increased metabolic activity of the local fibroblasts.", "contents": "[Activity of specific collagenases in developing granulomatous tissues]. Specific collagenases are activated rapidly in inflamed tissues. This activity reaches a higher level in acute inflammation than in chronic inflammation. It appears to be related to an increased metabolic activity of the local fibroblasts."} {"id": "PMID:172256", "title": "[Confirmation of the localization on human chromosome F19 of a structural gene of poliovirus receptors].", "content": "The study of permissivity for poliovirus and the study of enzymatic markers in man-mouse somatic cell hybrids presents a very positive correlation between the presence of the poliovirus receptor and the presence of a well known enzyme marker, the phosphoglucoseisomerase (GPI), localized on the human chromosome F 19.", "contents": "[Confirmation of the localization on human chromosome F19 of a structural gene of poliovirus receptors]. The study of permissivity for poliovirus and the study of enzymatic markers in man-mouse somatic cell hybrids presents a very positive correlation between the presence of the poliovirus receptor and the presence of a well known enzyme marker, the phosphoglucoseisomerase (GPI), localized on the human chromosome F 19."} {"id": "PMID:172257", "title": "[Transfer of the tetracycline-chloramphenicol plasmid in Clostridium perfringens].", "content": "Two plasmids which confer resistance to Tetracycline-Chloramphenicol and Erythromycine-Clindamycine were found in a strain of Clostridium perfringens. The plasmid (Tet-Chl) was shown to be transferable to sensitive strains of C. perfringens. The transfer experiments were made with the wild type strain or strains cured by one plasmid or the other as donor strains.", "contents": "[Transfer of the tetracycline-chloramphenicol plasmid in Clostridium perfringens]. Two plasmids which confer resistance to Tetracycline-Chloramphenicol and Erythromycine-Clindamycine were found in a strain of Clostridium perfringens. The plasmid (Tet-Chl) was shown to be transferable to sensitive strains of C. perfringens. The transfer experiments were made with the wild type strain or strains cured by one plasmid or the other as donor strains."} {"id": "PMID:172259", "title": "Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.", "content": "When studied on isolated rat mesenteric arteries perfused with Tyrode's solution, angiotensin I and angiotensin II (1 ng/ml), a synthetic tetradecapeptide renin substrate, and a purified hog renin substance (50-100 ng/ml) potentiated vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine without altering basal pressure. These agents produced a greater augmentation of the vasoconstrictor responses to nerve stimulation than to injected norepinephrine. The potentiation of vasoconstrictor responses to sympathetic nerve stimulation and injected norepinephrine which was elicited by renin substrate and angiotensin I was abolished by an inhibitor of angiotensin I-converting enzyme, SQ 20,881, and by an angiotensin II receptor antagonist, [Sar1-Ile8]angiotensin II. In contrast, the potentiating effect of angiotensin II was blocked only by the latter compound. We conclude that utilization of renin substrate within the vascular wall by renin or renin-like enzymes results in the formation of angiotensin I, which is converted to angiotensin II. Angiotensin in turn potentiates the vasoconstrictor responses to adrenergic stimuli presumably by augmenting release of the adrenergic transmitter and inhibiting its neuronal reuptake as well as by increasing vascular reactivity to norepinephrine.", "contents": "Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries. When studied on isolated rat mesenteric arteries perfused with Tyrode's solution, angiotensin I and angiotensin II (1 ng/ml), a synthetic tetradecapeptide renin substrate, and a purified hog renin substance (50-100 ng/ml) potentiated vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine without altering basal pressure. These agents produced a greater augmentation of the vasoconstrictor responses to nerve stimulation than to injected norepinephrine. The potentiation of vasoconstrictor responses to sympathetic nerve stimulation and injected norepinephrine which was elicited by renin substrate and angiotensin I was abolished by an inhibitor of angiotensin I-converting enzyme, SQ 20,881, and by an angiotensin II receptor antagonist, [Sar1-Ile8]angiotensin II. In contrast, the potentiating effect of angiotensin II was blocked only by the latter compound. We conclude that utilization of renin substrate within the vascular wall by renin or renin-like enzymes results in the formation of angiotensin I, which is converted to angiotensin II. Angiotensin in turn potentiates the vasoconstrictor responses to adrenergic stimuli presumably by augmenting release of the adrenergic transmitter and inhibiting its neuronal reuptake as well as by increasing vascular reactivity to norepinephrine."} {"id": "PMID:172260", "title": "Diagnosis of type III hyperlipoproteinemia by chromatography of plasma lipoproteins on columns containing agarose.", "content": "Agarose column chromatography has been used to separate plasma lipoproteins into very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Applied to the diagnosis of primary type III hyperlipoproteinemia, the procedure is capable of demonstrating three characteristic and specific changes from normality in the elution pattern of lipoproteins from patients with this condition. In the type III profile there is (a) incomplete separation of VLDL from putative LDL material, (b) early elution of the type III LDL with respect to a normal LDL marker, and (c) relative deficiency of type III LDL with elution characteristics of normal LDL. We advocate the use of this method in the diagnosis of type III hyperlipoproteinemia.", "contents": "Diagnosis of type III hyperlipoproteinemia by chromatography of plasma lipoproteins on columns containing agarose. Agarose column chromatography has been used to separate plasma lipoproteins into very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Applied to the diagnosis of primary type III hyperlipoproteinemia, the procedure is capable of demonstrating three characteristic and specific changes from normality in the elution pattern of lipoproteins from patients with this condition. In the type III profile there is (a) incomplete separation of VLDL from putative LDL material, (b) early elution of the type III LDL with respect to a normal LDL marker, and (c) relative deficiency of type III LDL with elution characteristics of normal LDL. We advocate the use of this method in the diagnosis of type III hyperlipoproteinemia."} {"id": "PMID:172261", "title": "Cholesterol metabolism in hypertriglyceridaemia and the effects of treatment.", "content": "The faecal output of bile acids and endogenous neutral steroids was increased in three hypertriglyceridaemic patients. One patient had familail type IIb, one had type IV and the third had type V hyperlipoproteinaemia. The hyperlipidaemia in the type IV and type V patients was associated with diabetes and a high alcohol intake. The plasma cholesterol and triglyceride concentrations and the faecal output of bile acids decreased significantly when the type IIb patient was given D-thyroxine plus propranolol, and when the type IV and type V patients were treated by withdrawal of alcohol, a low=carbohydrate diet and insulin or glibenclamide. The findings are discussed in relation to the possibility that hypertriglyceridaemia and increased bile acid synthesis in these patients have a common metabolic origin.", "contents": "Cholesterol metabolism in hypertriglyceridaemia and the effects of treatment. The faecal output of bile acids and endogenous neutral steroids was increased in three hypertriglyceridaemic patients. One patient had familail type IIb, one had type IV and the third had type V hyperlipoproteinaemia. The hyperlipidaemia in the type IV and type V patients was associated with diabetes and a high alcohol intake. The plasma cholesterol and triglyceride concentrations and the faecal output of bile acids decreased significantly when the type IIb patient was given D-thyroxine plus propranolol, and when the type IV and type V patients were treated by withdrawal of alcohol, a low=carbohydrate diet and insulin or glibenclamide. The findings are discussed in relation to the possibility that hypertriglyceridaemia and increased bile acid synthesis in these patients have a common metabolic origin."} {"id": "PMID:172263", "title": "The fluorimetric determination of ammonia in protein-free filtrates of human blood plasma.", "content": "Ammonia has been determined in filtrates of human plasma after precipitation of the proteins by perchloric acid. After restoration of the pH to around 7.5, addition of 2-oxoglutarate, NADH and glutamate dehydrogenase (GDH) convers the ammonia to L-glutamate with oxidation of the NADH to NAD. This latter reaction was utilised in two ways. In the first, reduction of native NADH fluorescence under the conditions of the GDH reaction provided a measure of ammonia concentration. In the second, residual NADH was destroyed by acid treatment, and the fluorescent product generated from NAD under strongly alkaline conditions was assayed. The optimal requirements for both methods were defined, their linearity and precision ascertained, and their relative merits compared. The first method was convenient for \"one-off\" estimations, and the second for larger batches. Ammonia concentration increased in plasma and in acid protein-free filtrates of plasma irrespective of the conditions of storage; however when the latter were neutralised, storage at -20 degrees C was effective. The distribution of plasma ammonia concentration in healthy subjects was log-normal. The range for males was 21-58 mumol/1 and for females 17-51 mumol/1; this difference was statistically significant (P less than 0.01).", "contents": "The fluorimetric determination of ammonia in protein-free filtrates of human blood plasma. Ammonia has been determined in filtrates of human plasma after precipitation of the proteins by perchloric acid. After restoration of the pH to around 7.5, addition of 2-oxoglutarate, NADH and glutamate dehydrogenase (GDH) convers the ammonia to L-glutamate with oxidation of the NADH to NAD. This latter reaction was utilised in two ways. In the first, reduction of native NADH fluorescence under the conditions of the GDH reaction provided a measure of ammonia concentration. In the second, residual NADH was destroyed by acid treatment, and the fluorescent product generated from NAD under strongly alkaline conditions was assayed. The optimal requirements for both methods were defined, their linearity and precision ascertained, and their relative merits compared. The first method was convenient for \"one-off\" estimations, and the second for larger batches. Ammonia concentration increased in plasma and in acid protein-free filtrates of plasma irrespective of the conditions of storage; however when the latter were neutralised, storage at -20 degrees C was effective. The distribution of plasma ammonia concentration in healthy subjects was log-normal. The range for males was 21-58 mumol/1 and for females 17-51 mumol/1; this difference was statistically significant (P less than 0.01)."} {"id": "PMID:172275", "title": "The radiology of excavated Saxon and medieval human remains from Winchester.", "content": "Radiography of many of the human bones discovered during the archeological excavations at Winchester has been an integral part of the study of the Saxon and medieval populations found there. Thus, a radiological study of bone pathology in successive populations from a single site spanning a period of 600 years is presented.", "contents": "The radiology of excavated Saxon and medieval human remains from Winchester. Radiography of many of the human bones discovered during the archeological excavations at Winchester has been an integral part of the study of the Saxon and medieval populations found there. Thus, a radiological study of bone pathology in successive populations from a single site spanning a period of 600 years is presented."} {"id": "PMID:172271", "title": "Ganglia of the nerve. Presentation of two unusual cases, a review of the literature, and a discussion of pathogenesis.", "content": "Two cases of intraneural ganglia are reported: the first reported involvement of the sciatic nerve and the first reported involvement of the tibial nerve in the tarsal tunnel. Both were successfully treated by excision with sparing the neural elements leading to neurological recovery. A review of the literature fails to reveal any consensus that lesions arise from normal synovial cavities. Incision, evacuation, and complete excision under magnification sparing neural elements gives satisfactory results. Excision of the nerve is not indicated. Pathologic examination suggests that the lesion arises by multicentric metaplasia of connective tissue elements of the nerve rather than by invasion.", "contents": "Ganglia of the nerve. Presentation of two unusual cases, a review of the literature, and a discussion of pathogenesis. Two cases of intraneural ganglia are reported: the first reported involvement of the sciatic nerve and the first reported involvement of the tibial nerve in the tarsal tunnel. Both were successfully treated by excision with sparing the neural elements leading to neurological recovery. A review of the literature fails to reveal any consensus that lesions arise from normal synovial cavities. Incision, evacuation, and complete excision under magnification sparing neural elements gives satisfactory results. Excision of the nerve is not indicated. Pathologic examination suggests that the lesion arises by multicentric metaplasia of connective tissue elements of the nerve rather than by invasion."} {"id": "PMID:172276", "title": "The angiographic evaluation of the internal carotid artery.", "content": "The importance of adequate evaluation of the internal carotid artery is stressed since pathology within it may mimic many intracranial diseases. Some of the many appearances seen on carotid angiography are described.", "contents": "The angiographic evaluation of the internal carotid artery. The importance of adequate evaluation of the internal carotid artery is stressed since pathology within it may mimic many intracranial diseases. Some of the many appearances seen on carotid angiography are described."} {"id": "PMID:172277", "title": "The effects of a diphosphonate and dietary calcium on the metabolism of vitamin D3 (cholecalciferol) in the chick.", "content": "1. Vitamin D-deficient chicks, maintained on a diet adequate in calcium and treated with ethane-1-hydroxy-1,1-diphosphonate for 2 days before a single oral dose of cholecalciferol (vitamin D3), converted the vitamin into 24,25-dihydroxycholecalciferol instead of into the normal metabolite 1,25-dihydroxycholecalciferol. 2. This inhibition of the renal 1-hydroxylase disappeared on withdrawal of the diphosphonate. 3. Kidneys from chicks given diphosphonate for 12 days converted 25-hydroxycholecalciferol into 24,25-dihydroxycholecalciferol on incubation in vitro. 4. The inhibition of the 1-hydroxylase was markedly accelerated by treating the birds with cholecalciferol. 5. No inhibition of renal 1-hydroxylation was observed in birds maintained on a diet low in calcium. 6. A possible mechanism producing this effect is discussed.", "contents": "The effects of a diphosphonate and dietary calcium on the metabolism of vitamin D3 (cholecalciferol) in the chick. 1. Vitamin D-deficient chicks, maintained on a diet adequate in calcium and treated with ethane-1-hydroxy-1,1-diphosphonate for 2 days before a single oral dose of cholecalciferol (vitamin D3), converted the vitamin into 24,25-dihydroxycholecalciferol instead of into the normal metabolite 1,25-dihydroxycholecalciferol. 2. This inhibition of the renal 1-hydroxylase disappeared on withdrawal of the diphosphonate. 3. Kidneys from chicks given diphosphonate for 12 days converted 25-hydroxycholecalciferol into 24,25-dihydroxycholecalciferol on incubation in vitro. 4. The inhibition of the 1-hydroxylase was markedly accelerated by treating the birds with cholecalciferol. 5. No inhibition of renal 1-hydroxylation was observed in birds maintained on a diet low in calcium. 6. A possible mechanism producing this effect is discussed."} {"id": "PMID:172278", "title": "Observations on the passage of apoproteins from plasma lipoproteins into peripheral lymph in two men.", "content": "1. The passage of radioactive apolipoproteins into lymph draining the foot was investigated in two men, each given a single intravenous injection of low-density lipoprotein containing 131I-labelled apoprotein B and of very-low-density lipoprotein containing 125I-labelled apoprotein A and apoprotein C. 2. Protein-bound 125I and 131I appeared in the lymph of both subjects. Immunoelectrophoresis of lymph lipoproteins against anti-(high-density lipoprotein) and anti-(low-density lipoprotein) showed the presence of apo-high-density lipoprotein and apo-low-density lipoprotein with faster mobilities than plasma high-density and low-density lipoprotein respectively. Most of the protein-bound 131I in lymph was recovered in the precipitin line formed by the apoprotein B-containing lipoprotein after immunoelectrophoresis. Polyacrylamide gel electrophoresis of the lymph lipoprotein fraction showed the presence of 125I-containing bands with mobilities similar to those of the apoprotein A of high-density lipoprotein and of three of the fast-moving C apoproteins. 3. These results suggest that most, if not all, of the apoproteins of plasma lipoproteins reach the interstitial fluids and that some lipoproteins undergo modification during their passage into peripheral lymph.", "contents": "Observations on the passage of apoproteins from plasma lipoproteins into peripheral lymph in two men. 1. The passage of radioactive apolipoproteins into lymph draining the foot was investigated in two men, each given a single intravenous injection of low-density lipoprotein containing 131I-labelled apoprotein B and of very-low-density lipoprotein containing 125I-labelled apoprotein A and apoprotein C. 2. Protein-bound 125I and 131I appeared in the lymph of both subjects. Immunoelectrophoresis of lymph lipoproteins against anti-(high-density lipoprotein) and anti-(low-density lipoprotein) showed the presence of apo-high-density lipoprotein and apo-low-density lipoprotein with faster mobilities than plasma high-density and low-density lipoprotein respectively. Most of the protein-bound 131I in lymph was recovered in the precipitin line formed by the apoprotein B-containing lipoprotein after immunoelectrophoresis. Polyacrylamide gel electrophoresis of the lymph lipoprotein fraction showed the presence of 125I-containing bands with mobilities similar to those of the apoprotein A of high-density lipoprotein and of three of the fast-moving C apoproteins. 3. These results suggest that most, if not all, of the apoproteins of plasma lipoproteins reach the interstitial fluids and that some lipoproteins undergo modification during their passage into peripheral lymph."} {"id": "PMID:172279", "title": "Serological diagnosis of infection with the putative bovine leukemia virus.", "content": "We report on an accurate, rapid and inexpensive test for the identification of animals infected with the Bovine C-type virus (BLV). The test involves the detection of serum antibodies to BLV using the immunofluorescent (IF) technique on acetone-fixed, infected cells. The specificity of the test was demonstrated by the fact that virus was found by electron microscopy in 90% of cattle showing positive reactions. In contrast, virus was not found despite extensive examination in antibody negative animals. Thus, the presence of IF antibody is an accurate indicator of current rather than past BLV infection. In order for the IF test to be specific it is of critical importance that the target cells used are infected only with BLV. BLV antibodies can also be detected by the immunoprecipitation (Ouchterlony) technique. However, a significant proportion of BLV infected animals showing positive reactions in the IF test failed to show precipitin antibodies to the virus. Likewise, BLV infection was demonstrated by both the IF test and electron microscopy in many animals with persistently normal levels of blood lymphocytes. Thus, neither the precipitin test nor the blood lymphocyte count (Bendixen's key) can be used to rule out BLV infection.", "contents": "Serological diagnosis of infection with the putative bovine leukemia virus. We report on an accurate, rapid and inexpensive test for the identification of animals infected with the Bovine C-type virus (BLV). The test involves the detection of serum antibodies to BLV using the immunofluorescent (IF) technique on acetone-fixed, infected cells. The specificity of the test was demonstrated by the fact that virus was found by electron microscopy in 90% of cattle showing positive reactions. In contrast, virus was not found despite extensive examination in antibody negative animals. Thus, the presence of IF antibody is an accurate indicator of current rather than past BLV infection. In order for the IF test to be specific it is of critical importance that the target cells used are infected only with BLV. BLV antibodies can also be detected by the immunoprecipitation (Ouchterlony) technique. However, a significant proportion of BLV infected animals showing positive reactions in the IF test failed to show precipitin antibodies to the virus. Likewise, BLV infection was demonstrated by both the IF test and electron microscopy in many animals with persistently normal levels of blood lymphocytes. Thus, neither the precipitin test nor the blood lymphocyte count (Bendixen's key) can be used to rule out BLV infection."} {"id": "PMID:172281", "title": "Interaction of ethacrynic acid with control sites of renal glucose metabolism.", "content": "Ethacrynic acid stimulates in vitro concentration dependent renal gluconeogenesis from substrates which enter the gluconeogenic pathway at the level of the triosephosphates like glycerol or fructose or from substrates which have to pass the oxaloacetate shuttle like pyruvate or from intermediary products of fatty acid oxydation or citrate cycle. Our results suggest that a site of action of ethacrynic acid in this metabolic aspect is the enzyme system fructose diphosphatase/frutose-6-phosphate kinase and eventually additionally pyruvate carboxylase.", "contents": "Interaction of ethacrynic acid with control sites of renal glucose metabolism. Ethacrynic acid stimulates in vitro concentration dependent renal gluconeogenesis from substrates which enter the gluconeogenic pathway at the level of the triosephosphates like glycerol or fructose or from substrates which have to pass the oxaloacetate shuttle like pyruvate or from intermediary products of fatty acid oxydation or citrate cycle. Our results suggest that a site of action of ethacrynic acid in this metabolic aspect is the enzyme system fructose diphosphatase/frutose-6-phosphate kinase and eventually additionally pyruvate carboxylase."} {"id": "PMID:172283", "title": "Metabolic patterns in various structures of the rat nephron. The distribution of enzymes of carbohydrate metabolism.", "content": "By means of the microdissection technique applied on kidney tissue, the following results were obtained: Hexokinase, an enzyme of glycolysis, revealed a low activity in the proximal and a high activity in the distal tubule. This distribution pattern is consistent with the finding that glucose is the main fuel for the distal tubule. Glucose-6-phosphatase, an enzyme of gluconeogenesis, demonstrates a significant activity in the distal tubule and in the glomerulus. Both structures are, however, no glucose producers. Phosphoenolpyruvate carboxykinase, the key enzyme of gluconeogenesis, is found only in the segments of the proximal tubule. The distal tubule lacks any activity. This is also the case during starvation and metabolic acidosis when gluconeogenesis is stimulated. Glutamic dehydrogenase, -an enzyme possibly connected with ammoniagenesis-, malate- and lactate dehydrogenase-, enzymes involved with hydrogen transfer through the mitochondrial membrane-, showed a close parallelism to phosphoenolpyruvate carboxykinase in their distribution along the proximal tubule. The bidirectional function of glyceraldehyde-P dehydrogenase is well documented by the close correlation to phosphoenolpyruvate carboxykinase (gluconeogenesis) in the proximal tubule and to pyruvic kinase (glycolysis) in the distal tubule.", "contents": "Metabolic patterns in various structures of the rat nephron. The distribution of enzymes of carbohydrate metabolism. By means of the microdissection technique applied on kidney tissue, the following results were obtained: Hexokinase, an enzyme of glycolysis, revealed a low activity in the proximal and a high activity in the distal tubule. This distribution pattern is consistent with the finding that glucose is the main fuel for the distal tubule. Glucose-6-phosphatase, an enzyme of gluconeogenesis, demonstrates a significant activity in the distal tubule and in the glomerulus. Both structures are, however, no glucose producers. Phosphoenolpyruvate carboxykinase, the key enzyme of gluconeogenesis, is found only in the segments of the proximal tubule. The distal tubule lacks any activity. This is also the case during starvation and metabolic acidosis when gluconeogenesis is stimulated. Glutamic dehydrogenase, -an enzyme possibly connected with ammoniagenesis-, malate- and lactate dehydrogenase-, enzymes involved with hydrogen transfer through the mitochondrial membrane-, showed a close parallelism to phosphoenolpyruvate carboxykinase in their distribution along the proximal tubule. The bidirectional function of glyceraldehyde-P dehydrogenase is well documented by the close correlation to phosphoenolpyruvate carboxykinase (gluconeogenesis) in the proximal tubule and to pyruvic kinase (glycolysis) in the distal tubule."} {"id": "PMID:172293", "title": "Assignment of the gene for human uridine monophosphate kinase to chromosome 1 using somatic cell hybrid clone panels.", "content": "Evidence from mouse-human somatic cell hybrids is presented for the assignment of the gene for uridine monophosphate kinase (ATP: nucleoside monophosphate phosphotransferase, E.C. 2.7.4.4) to human chromosome 1. The use of the \"clone panel\" in this determination and its value as a systematic method for gene mapping is discussed.", "contents": "Assignment of the gene for human uridine monophosphate kinase to chromosome 1 using somatic cell hybrid clone panels. Evidence from mouse-human somatic cell hybrids is presented for the assignment of the gene for uridine monophosphate kinase (ATP: nucleoside monophosphate phosphotransferase, E.C. 2.7.4.4) to human chromosome 1. The use of the \"clone panel\" in this determination and its value as a systematic method for gene mapping is discussed."} {"id": "PMID:172297", "title": "A new method of in situ hybridization.", "content": "A new method for gene mapping at the chromosome level using in situ hybridization and scanning electron microscopy is described and has been applied to mapping the rRNA genes of Drosophila melanogaster. Biotin is covalently attached to Drosophila rRNA via a cytochrome c bridge at a ratio of one cytochrome-biotin per 130 nucleotides by a chemical procedure. Polymethacrylate spheres with a diameter of ca. 60 nm are prepared by emulsion polymerization and are covalently attached to the protein avidin at a ratio of 5-20 avidins per sphere. The biotin-labeled rRNA is hybridized to denatured DNA in a chromosome squash. Upon incubation with a sphere solution, some of the biotin sites become labeled with spheres because of the strong non-covalent interaction between biotin and avidin. The chromosome squash is examined in the scanning electron microscope (SEM). Polymer spheres, which are visible in the SEM, are observed to label the nucleolus, where the rRNA genes are located.", "contents": "A new method of in situ hybridization. A new method for gene mapping at the chromosome level using in situ hybridization and scanning electron microscopy is described and has been applied to mapping the rRNA genes of Drosophila melanogaster. Biotin is covalently attached to Drosophila rRNA via a cytochrome c bridge at a ratio of one cytochrome-biotin per 130 nucleotides by a chemical procedure. Polymethacrylate spheres with a diameter of ca. 60 nm are prepared by emulsion polymerization and are covalently attached to the protein avidin at a ratio of 5-20 avidins per sphere. The biotin-labeled rRNA is hybridized to denatured DNA in a chromosome squash. Upon incubation with a sphere solution, some of the biotin sites become labeled with spheres because of the strong non-covalent interaction between biotin and avidin. The chromosome squash is examined in the scanning electron microscope (SEM). Polymer spheres, which are visible in the SEM, are observed to label the nucleolus, where the rRNA genes are located."} {"id": "PMID:172298", "title": "Circadian rhythm of urinary 17-hydroxycorticosteroids during metyrapone-induced ACTH release in normal subjects.", "content": "The circadian rhythm of urinary 17-OHCS was studied in nine normal subjects before and after oral metyrapone administration (750 mg every 4 hrs over a period of 24 hrs). The test was carried out twice in each subject with a shift of 12 hrs in the time of first administration (0800-test and 2000-test). For data from serial measurements of steroid metabolites on urine collected at 2-h intervals, the least squares fit of a 24-h cosine curve allowed the demonstration of a rhythm both in control conditions and during the 48-h span following metyrapone administration. Circadian acrophases were substantially similar. Total urinary 17-OHCS output in the first 24-h day following metyrapone was higher in the 2000-test as compared with the 0800-test (P less than .001). Conversely, in the second 24-h day, higher values were obtained in the 0800-test (P less than .025). The combined 48-h exretion, however, was identical in the two groups. The results suggest a time-limited action of metyrapone upon the pituitary-adrenal axis, since the increased excretion of 17-OHCS seems essentially accounted for by an exaggerated impulsive phase of ACTH secretion during the early morning hours.", "contents": "Circadian rhythm of urinary 17-hydroxycorticosteroids during metyrapone-induced ACTH release in normal subjects. The circadian rhythm of urinary 17-OHCS was studied in nine normal subjects before and after oral metyrapone administration (750 mg every 4 hrs over a period of 24 hrs). The test was carried out twice in each subject with a shift of 12 hrs in the time of first administration (0800-test and 2000-test). For data from serial measurements of steroid metabolites on urine collected at 2-h intervals, the least squares fit of a 24-h cosine curve allowed the demonstration of a rhythm both in control conditions and during the 48-h span following metyrapone administration. Circadian acrophases were substantially similar. Total urinary 17-OHCS output in the first 24-h day following metyrapone was higher in the 2000-test as compared with the 0800-test (P less than .001). Conversely, in the second 24-h day, higher values were obtained in the 0800-test (P less than .025). The combined 48-h exretion, however, was identical in the two groups. The results suggest a time-limited action of metyrapone upon the pituitary-adrenal axis, since the increased excretion of 17-OHCS seems essentially accounted for by an exaggerated impulsive phase of ACTH secretion during the early morning hours."} {"id": "PMID:172307", "title": "[Occult nasopharyngeal carcinoma (author's transl)].", "content": "Clinical and histological examination of a cervical lymph node, removed from a 15-year-old boy, revealed nasopharyngeal carcinoma as the probable diagnosis. But the decisive diagnostic pointer was a markedly raised Epstein-Barr virus antibody titre, which gives the diagnosis at a time when there may not as yet be clinical evidence of carcinoma. Serial serum titre determinations are of prognostic value: with increasing spread of the tumour there is a rise in antibody titre. Autopsy confirmed that the nasopharynx had been the site of the primary tumour.", "contents": "[Occult nasopharyngeal carcinoma (author's transl)]. Clinical and histological examination of a cervical lymph node, removed from a 15-year-old boy, revealed nasopharyngeal carcinoma as the probable diagnosis. But the decisive diagnostic pointer was a markedly raised Epstein-Barr virus antibody titre, which gives the diagnosis at a time when there may not as yet be clinical evidence of carcinoma. Serial serum titre determinations are of prognostic value: with increasing spread of the tumour there is a rise in antibody titre. Autopsy confirmed that the nasopharynx had been the site of the primary tumour."} {"id": "PMID:172309", "title": "Beclomethasone dipropionate inhaler: a review of its pharmacology, therapeutic value and adverse effects. I: Asthma.", "content": "Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly.", "contents": "Beclomethasone dipropionate inhaler: a review of its pharmacology, therapeutic value and adverse effects. I: Asthma. Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly."} {"id": "PMID:172310", "title": "Cyclic AMP response of isolated Snell adrenocortical carcinoma 494 cells to trophic hormones and other substances.", "content": "Suspensions of viable cells were prepared from solid tumor of the Snell adrenocortical carcinoma 494 without the use of proteolytic enzymes. Cyclic AMP formation in these cells was stimulated by ACTH, LH, FSH and TSH but not by prostaglandins (E1, E2, F1alpha and F2alpha), insulin and secretin. Glucagon tested at a single dose level of 50 mug increased cyclic AMP to about 65% of the maximum amounts obtained with ACTH. When Ca++ was omitted from the incubation medium, the response to ACTH was considerably reduced while that to LH was essentially unchanged. Low concentrations of EGTA (0.3 MM) abolished the ACTH response almost completely but caused only a partial reduction in the response to LH; as much as 10 mM EGTA was required to obtain complete inhibition of the latter.", "contents": "Cyclic AMP response of isolated Snell adrenocortical carcinoma 494 cells to trophic hormones and other substances. Suspensions of viable cells were prepared from solid tumor of the Snell adrenocortical carcinoma 494 without the use of proteolytic enzymes. Cyclic AMP formation in these cells was stimulated by ACTH, LH, FSH and TSH but not by prostaglandins (E1, E2, F1alpha and F2alpha), insulin and secretin. Glucagon tested at a single dose level of 50 mug increased cyclic AMP to about 65% of the maximum amounts obtained with ACTH. When Ca++ was omitted from the incubation medium, the response to ACTH was considerably reduced while that to LH was essentially unchanged. Low concentrations of EGTA (0.3 MM) abolished the ACTH response almost completely but caused only a partial reduction in the response to LH; as much as 10 mM EGTA was required to obtain complete inhibition of the latter."} {"id": "PMID:172311", "title": "Cyclic AMP in the thyroid of the rat fed prophylthiouracil: in vitro unresponsiveness to thyrotropin.", "content": "Fragments of thyroid from rats fed Purina +0.1% propylthiouracil were incubated in vitro and the concentration of cyclic AMP measured. The normal gland showed a 3-fold increase in cyclic AMP with 50 mU thyrotropin per ml or 10(-4) M prostaglandin E1; tissue from rats fed propylthiouracil for 10 days to 6 months responded to prostaglandin E1 but not to thyrotropin. Feeding Purina without propylthiouracil for 1 month after 5 months of goitrogen restored thyrotropin-responsiveness, as did, to a lesser extent, injection of triiodothyronine, 50 mug twice daily for 5 days.", "contents": "Cyclic AMP in the thyroid of the rat fed prophylthiouracil: in vitro unresponsiveness to thyrotropin. Fragments of thyroid from rats fed Purina +0.1% propylthiouracil were incubated in vitro and the concentration of cyclic AMP measured. The normal gland showed a 3-fold increase in cyclic AMP with 50 mU thyrotropin per ml or 10(-4) M prostaglandin E1; tissue from rats fed propylthiouracil for 10 days to 6 months responded to prostaglandin E1 but not to thyrotropin. Feeding Purina without propylthiouracil for 1 month after 5 months of goitrogen restored thyrotropin-responsiveness, as did, to a lesser extent, injection of triiodothyronine, 50 mug twice daily for 5 days."} {"id": "PMID:172312", "title": "Inhibition of a parathyroid hormone-stimulated renal adenylate cyclase by cyclic AMP.", "content": "Plasma membranes were isolated from bovine renal cortex. This particulate, adenylate cyclase-containing fraction was stimulated to produce cyclic AMP by parathyroid hormone and fluoride. When the time-course of adenylate cyclase activity was investigated, it was found that while PTH-stimulated cyclic AMP production comes to a halt in about 15 minutes after the initiation of the reaction, fluoride-stimulated activity continues unabated for at least an hour. Experiments to determine the cause of this showed that the cyclase enzyme is not degraded under our experimental conditions, but is inhibited by a soluble, unbound product of the reaction which requires ATP for its synthesis. In our experiments degradation of parathyroid hormone was relatively slow and could not account for the rapid inhibition of PTH-stimulated cyclase activity. Of the various agents tested, cyclic AMP was found capable of inhibiting PTH-stimulated cyclic AMP production by our purified membrane preparation. Half-maximal inhibition was observed at around 10(-6) M concentrations of the nucleotide. Pyrophosphate, adenosine, 5'-AMP and ADP had no effects. The significance of these results in relation to the regulation of adenylate cyclase activity is discussed.", "contents": "Inhibition of a parathyroid hormone-stimulated renal adenylate cyclase by cyclic AMP. Plasma membranes were isolated from bovine renal cortex. This particulate, adenylate cyclase-containing fraction was stimulated to produce cyclic AMP by parathyroid hormone and fluoride. When the time-course of adenylate cyclase activity was investigated, it was found that while PTH-stimulated cyclic AMP production comes to a halt in about 15 minutes after the initiation of the reaction, fluoride-stimulated activity continues unabated for at least an hour. Experiments to determine the cause of this showed that the cyclase enzyme is not degraded under our experimental conditions, but is inhibited by a soluble, unbound product of the reaction which requires ATP for its synthesis. In our experiments degradation of parathyroid hormone was relatively slow and could not account for the rapid inhibition of PTH-stimulated cyclase activity. Of the various agents tested, cyclic AMP was found capable of inhibiting PTH-stimulated cyclic AMP production by our purified membrane preparation. Half-maximal inhibition was observed at around 10(-6) M concentrations of the nucleotide. Pyrophosphate, adenosine, 5'-AMP and ADP had no effects. The significance of these results in relation to the regulation of adenylate cyclase activity is discussed."} {"id": "PMID:172314", "title": "Regulation of enzymes of serine and one-carbon metabolism by testosterone in rat prostate, liver, and kidney.", "content": "A significant decrease in the specific activity of 3 enzymes of serine and one-carbon metabolism (3-phosphoglycerate dehydrgenase, phosphoserine phosphatase, and serine hydroxy-methyltransferase) was found in the rat prostate gland with castration. A single injection of testosterone propionate to rats 3 days after castration resulted in a significant increase in the 3 enzyme activities within 24 h. This increase in specific activity was maximal 72 h after injection of testosterone in the case of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase. When cycloheximide was administered in conjunction with testosterone, the increase in 3-phosphoglycerate dehydrogenase and serine hydroxy-methyltransferase activity was significantly reduced compared to injection of testosterone alone. N6, O2'-dibutyryl adenosine-3',5'-cyclic monophosphate [(Bu)2 cAMP] and theophylline injected at 8 h intervals to rats 3 days after castration failed to mimic the action of testosterone on these 3 enzymes 24 and 72 h after beginning injections. Castration had no effect on the specific activity of these enzymes in the kidney; however, 3-phosphoglycerate dehydrogenase was significantly diminished in the liver 6 days after castration. A single injection of testosterone to rats 3 days after castration restored the activity to sham-operated levels. Serine hydroxy-methyltransferase and phosphoserine phosphatase activity in the liver were unaffected 6 days after castration. Thus testosterone exerts a regulatory role on serine and one-carbon metabolism in the prostate and liver which (Bu), cAMP is unable to minic.", "contents": "Regulation of enzymes of serine and one-carbon metabolism by testosterone in rat prostate, liver, and kidney. A significant decrease in the specific activity of 3 enzymes of serine and one-carbon metabolism (3-phosphoglycerate dehydrgenase, phosphoserine phosphatase, and serine hydroxy-methyltransferase) was found in the rat prostate gland with castration. A single injection of testosterone propionate to rats 3 days after castration resulted in a significant increase in the 3 enzyme activities within 24 h. This increase in specific activity was maximal 72 h after injection of testosterone in the case of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase. When cycloheximide was administered in conjunction with testosterone, the increase in 3-phosphoglycerate dehydrogenase and serine hydroxy-methyltransferase activity was significantly reduced compared to injection of testosterone alone. N6, O2'-dibutyryl adenosine-3',5'-cyclic monophosphate [(Bu)2 cAMP] and theophylline injected at 8 h intervals to rats 3 days after castration failed to mimic the action of testosterone on these 3 enzymes 24 and 72 h after beginning injections. Castration had no effect on the specific activity of these enzymes in the kidney; however, 3-phosphoglycerate dehydrogenase was significantly diminished in the liver 6 days after castration. A single injection of testosterone to rats 3 days after castration restored the activity to sham-operated levels. Serine hydroxy-methyltransferase and phosphoserine phosphatase activity in the liver were unaffected 6 days after castration. Thus testosterone exerts a regulatory role on serine and one-carbon metabolism in the prostate and liver which (Bu), cAMP is unable to minic."} {"id": "PMID:172315", "title": "A direct effect of testosterone on muscle cells in tissue culture.", "content": "A direct effect of physiological levels of testosterone on skeletal muscle cells in tissue culture is reported. The effect is a 25% stimulation of labeling index by radioautographic analysis of cultures following incubation with [3H]thymidine at the end of a 48-h exposure to 10(-8)M testosterone in 2% gelding serum. This stimulation was observed in primary myoblasts, an established myogenic cell line (Yaffe's L6 cells), and muscle fibroblasts. The effect was specific for testosterone: the labeling index did not change significantly from control values when estradiol, 5beta-pregnanediol, androstenedione, or dihydrotestosterone were added, although small increases were noted in the latter two cases. The effect on the labeling index was localized as a decrease in time spent in the G1 phase of the cell cycle, which decreased about 30% in muscle cells exposed to testosterone. This first report of an effect of testosterone on isolated muscle cells, coupled with the recent description of a receptor for anabolic steroids in muscle cytoplasm, indicates that the effects of male sex hormones result from a direct interaction with muscle rather than from a primary interaction with some other tissue.", "contents": "A direct effect of testosterone on muscle cells in tissue culture. A direct effect of physiological levels of testosterone on skeletal muscle cells in tissue culture is reported. The effect is a 25% stimulation of labeling index by radioautographic analysis of cultures following incubation with [3H]thymidine at the end of a 48-h exposure to 10(-8)M testosterone in 2% gelding serum. This stimulation was observed in primary myoblasts, an established myogenic cell line (Yaffe's L6 cells), and muscle fibroblasts. The effect was specific for testosterone: the labeling index did not change significantly from control values when estradiol, 5beta-pregnanediol, androstenedione, or dihydrotestosterone were added, although small increases were noted in the latter two cases. The effect on the labeling index was localized as a decrease in time spent in the G1 phase of the cell cycle, which decreased about 30% in muscle cells exposed to testosterone. This first report of an effect of testosterone on isolated muscle cells, coupled with the recent description of a receptor for anabolic steroids in muscle cytoplasm, indicates that the effects of male sex hormones result from a direct interaction with muscle rather than from a primary interaction with some other tissue."} {"id": "PMID:172316", "title": "The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)).", "content": "The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway.", "contents": "The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)). The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway."} {"id": "PMID:172317", "title": "Renal medullary adenylate cyclase in rats with hypothalamic diabetes insipidus.", "content": "The activities of enzymes related to the cellular action of vasopressin as well as the activities of other enzymes were studied in an animal model of hypothalamic diabetes insipidus. Rats with hereditary hypothalamic diabetes insipidus (homozygotes of Bratteboro strain) were found to have significantly lower renal medullary adenylate cyclase activity, either basal activity or activity stimulated by vasopressin, as compared with controls (heterozygotes of the same strain). There were no differences between the two strains in the activities of cyclic AMP phosphodiesterase, other hormone-sensitive adenylate cyclases, or the other renal medullary enzymes studied, which are apparently unrelated to the vasopressin action. The treatment of rats with hereditary hypothalamic diabetes insipidus with exogenous vasopressin increased the activity of renal medullary adenylate cyclase stimulated in vitro by maximal doses of vasopressin, but had no effect on the basal activity of adenylate cyclase or on the activity of cyclic AMP phosphodiesterase. This suggests that low adenylate cyclase activity in the renal medulla of rats with diabetes insipidus may be related to the subnormal concentrating ability observed in these animals.", "contents": "Renal medullary adenylate cyclase in rats with hypothalamic diabetes insipidus. The activities of enzymes related to the cellular action of vasopressin as well as the activities of other enzymes were studied in an animal model of hypothalamic diabetes insipidus. Rats with hereditary hypothalamic diabetes insipidus (homozygotes of Bratteboro strain) were found to have significantly lower renal medullary adenylate cyclase activity, either basal activity or activity stimulated by vasopressin, as compared with controls (heterozygotes of the same strain). There were no differences between the two strains in the activities of cyclic AMP phosphodiesterase, other hormone-sensitive adenylate cyclases, or the other renal medullary enzymes studied, which are apparently unrelated to the vasopressin action. The treatment of rats with hereditary hypothalamic diabetes insipidus with exogenous vasopressin increased the activity of renal medullary adenylate cyclase stimulated in vitro by maximal doses of vasopressin, but had no effect on the basal activity of adenylate cyclase or on the activity of cyclic AMP phosphodiesterase. This suggests that low adenylate cyclase activity in the renal medulla of rats with diabetes insipidus may be related to the subnormal concentrating ability observed in these animals."} {"id": "PMID:172318", "title": "Induction of human endometrial estradiol dehydrogenase by progestins.", "content": "Estradiol-17beta dehydrogenase activity in proliferative human endometrium (average of 1.5 nmole of estrone formed from estradiol/mg protein/h) was stimulated as much as as 6-fold during incubations of tissue slices in culture medium containing progesterone. Stimulation was already detectable at 7 h and the highest activity values were reached at 48-72 h of incubation in the presence of excess progesterone. Maximal stimulation was achieved with concentrations of the hormone of 0.25 mug/ml or higher. At concentrations approximately equal to midluteal plasma levels (20 ng/ml) more than 50% of the maximal response was observed. Norgestrel (17alpha-ethynyl-18-methyl-19-nortestosterone) was also effective in inducing enzymatic activity. The similarity of the effects obtained with progesterone (a possible substrate for estradiol dehydrogenase) and the synthetic progestin indicates that the stimulation of enzymatic activity was not due to substrate induction. Addition of estradiol to the culture medium had no influence on the activity of the enzyme. The induction of estradiol dehydrogenase by progesterone was inhibited by puromycin or actinomycin D. These observations indicate that progestational agents increase the rate of de novo synthesis of the enzyme. Stimulation of endometrial estradiol dehydrogenase was also observed after 2-3 day oral administration of medroxyprogesterone acetate to women in the follicular phase. In contrast, the enzymatic activity in endometrium obtained from women taking estrogens was found to be as low as in normal proliferative tissue. These in vitro and in vivo results point to progesterone as the agent responsible for the 10-fold increase in endometrial estradiol dehydrogenase activity observed during the luteal phase in menstruating women. Data obtained from superfusion studies of estrogen dynamics in endometrium indicate that changes in enzyme concentrations may play a physiologic role in the regulation of tissue levels of estradiol.", "contents": "Induction of human endometrial estradiol dehydrogenase by progestins. Estradiol-17beta dehydrogenase activity in proliferative human endometrium (average of 1.5 nmole of estrone formed from estradiol/mg protein/h) was stimulated as much as as 6-fold during incubations of tissue slices in culture medium containing progesterone. Stimulation was already detectable at 7 h and the highest activity values were reached at 48-72 h of incubation in the presence of excess progesterone. Maximal stimulation was achieved with concentrations of the hormone of 0.25 mug/ml or higher. At concentrations approximately equal to midluteal plasma levels (20 ng/ml) more than 50% of the maximal response was observed. Norgestrel (17alpha-ethynyl-18-methyl-19-nortestosterone) was also effective in inducing enzymatic activity. The similarity of the effects obtained with progesterone (a possible substrate for estradiol dehydrogenase) and the synthetic progestin indicates that the stimulation of enzymatic activity was not due to substrate induction. Addition of estradiol to the culture medium had no influence on the activity of the enzyme. The induction of estradiol dehydrogenase by progesterone was inhibited by puromycin or actinomycin D. These observations indicate that progestational agents increase the rate of de novo synthesis of the enzyme. Stimulation of endometrial estradiol dehydrogenase was also observed after 2-3 day oral administration of medroxyprogesterone acetate to women in the follicular phase. In contrast, the enzymatic activity in endometrium obtained from women taking estrogens was found to be as low as in normal proliferative tissue. These in vitro and in vivo results point to progesterone as the agent responsible for the 10-fold increase in endometrial estradiol dehydrogenase activity observed during the luteal phase in menstruating women. Data obtained from superfusion studies of estrogen dynamics in endometrium indicate that changes in enzyme concentrations may play a physiologic role in the regulation of tissue levels of estradiol."} {"id": "PMID:172319", "title": "Binding of insulin to thymocytes from suckling and hypophysectomized rats: evidence for two mechanisms regulating insulin sensitivity.", "content": "Insulin more effectively increased amino acid influx into thymocytes isolated from insulin-sensitive suckling and hypophysectomized rats than into cells obtained from normal adult animals. Thymocytes from hypophysectomized adult rats bound more insulin than did cells from sham-operated controls, suggesting that insulin sensitivity in this condition was due to an increase in the number of insulin receptors. In contrast, thymocytes from suckling rats bound the same amount of insulin as did cells from adult animals, suggesting that in this instance insulin sensitivity was the result of changes in events subsequent to the binding of insulin.", "contents": "Binding of insulin to thymocytes from suckling and hypophysectomized rats: evidence for two mechanisms regulating insulin sensitivity. Insulin more effectively increased amino acid influx into thymocytes isolated from insulin-sensitive suckling and hypophysectomized rats than into cells obtained from normal adult animals. Thymocytes from hypophysectomized adult rats bound more insulin than did cells from sham-operated controls, suggesting that insulin sensitivity in this condition was due to an increase in the number of insulin receptors. In contrast, thymocytes from suckling rats bound the same amount of insulin as did cells from adult animals, suggesting that in this instance insulin sensitivity was the result of changes in events subsequent to the binding of insulin."} {"id": "PMID:172320", "title": "The role of the pentose phosphate shunt in thyrotropin-induced thyroid hormone secretion: in vivo and vitro studies with 6-aminonicotinamide in mouse thyroids.", "content": "The possible role of the pentose phosphate shunt in thyroid hormone secretion was investigated in vivo and in vitro with mouse thyroid glands. Thyroidal endocytosis in response to TSH, a step of thyroid hormone secretion, was evaluated for its dependency upon the pentose phosphate shunt by using 6-aminonicotinamide (6-AN), an antimetabolite in the synthesis of pyridine nucleotides. Formation of 14CO2 from glucose labeled either in the C-1 or C-6 position was studied to estimate the pentose phosphate shunt activity. A dose of 6-AN markedly reduced oxidation of [1-14C]glucose but did not affect that of [6-14C]glucose induced by TSH. Concomitantly there was a marked decrease in thyroidal endocytotic response to TSH. These inhibitions by 6-AN were completely abolished by the pretreatment with nicotinamide. Methylene blue, which oxidizes NADPH and thus stimulates activity of the pentose shunt, significantly depressed thyroidal endocytosis in response to TSH in vitro. These inhibitions of colloid droplet formation by 6-AN or methylene blue were not manifested against dibutyryl cyclic AMP stimulation. Furthermore, a dose of 6-AN, which seems to inhibit only the pentose phosphate shunt, markedly depressed TSH-induced formation of cyclic amp. These findings suggest that the pentose phosphate shunt might play an important role in triggering TSH stimulation of thyroid hormone secretion by supplying NADPH, and further, that NADPH dependency in thyroid hormone secretion is at a site prior to the generation of cyclic AMP.", "contents": "The role of the pentose phosphate shunt in thyrotropin-induced thyroid hormone secretion: in vivo and vitro studies with 6-aminonicotinamide in mouse thyroids. The possible role of the pentose phosphate shunt in thyroid hormone secretion was investigated in vivo and in vitro with mouse thyroid glands. Thyroidal endocytosis in response to TSH, a step of thyroid hormone secretion, was evaluated for its dependency upon the pentose phosphate shunt by using 6-aminonicotinamide (6-AN), an antimetabolite in the synthesis of pyridine nucleotides. Formation of 14CO2 from glucose labeled either in the C-1 or C-6 position was studied to estimate the pentose phosphate shunt activity. A dose of 6-AN markedly reduced oxidation of [1-14C]glucose but did not affect that of [6-14C]glucose induced by TSH. Concomitantly there was a marked decrease in thyroidal endocytotic response to TSH. These inhibitions by 6-AN were completely abolished by the pretreatment with nicotinamide. Methylene blue, which oxidizes NADPH and thus stimulates activity of the pentose shunt, significantly depressed thyroidal endocytosis in response to TSH in vitro. These inhibitions of colloid droplet formation by 6-AN or methylene blue were not manifested against dibutyryl cyclic AMP stimulation. Furthermore, a dose of 6-AN, which seems to inhibit only the pentose phosphate shunt, markedly depressed TSH-induced formation of cyclic amp. These findings suggest that the pentose phosphate shunt might play an important role in triggering TSH stimulation of thyroid hormone secretion by supplying NADPH, and further, that NADPH dependency in thyroid hormone secretion is at a site prior to the generation of cyclic AMP."} {"id": "PMID:172321", "title": "Diabetes insipidus and galactorrhea caused by histiocytosis X.", "content": "A 44-year-old woman with diabetes insipidus of 3 years duration was found to have histiocytosis X. This was based on clinical, radiological and pathological findings consistent with the diagnosis. Furthermore, she developed spontaneous galactorrhea during the course. Endocrine studies of hypothalamic-pituitary function revealed completely impaired secretion of gonadotropin, growth hormone and anti-diuretic hormone, and possible partial impairment of adrenocorticotropic hormone secretion, while thyroid stimulating hormone secretion remained intact. Persistently elevated plasma levels of human prolactin were also demonstrated, which were unaffected by administration of either thyrotropin releasing hormone, l-DOPA or water loading, but suppressed significantly by CB-154, an ergot alkaloid. These results suggest that abnormalities of the patient's endocrine function may be mainly accounted for by a single hypothalamic lesion.", "contents": "Diabetes insipidus and galactorrhea caused by histiocytosis X. A 44-year-old woman with diabetes insipidus of 3 years duration was found to have histiocytosis X. This was based on clinical, radiological and pathological findings consistent with the diagnosis. Furthermore, she developed spontaneous galactorrhea during the course. Endocrine studies of hypothalamic-pituitary function revealed completely impaired secretion of gonadotropin, growth hormone and anti-diuretic hormone, and possible partial impairment of adrenocorticotropic hormone secretion, while thyroid stimulating hormone secretion remained intact. Persistently elevated plasma levels of human prolactin were also demonstrated, which were unaffected by administration of either thyrotropin releasing hormone, l-DOPA or water loading, but suppressed significantly by CB-154, an ergot alkaloid. These results suggest that abnormalities of the patient's endocrine function may be mainly accounted for by a single hypothalamic lesion."} {"id": "PMID:172322", "title": "ACTH secretion during sleep in a patient with Nelson's syndrome.", "content": "Plasma ACTH determinations were made by radioimmunoassay, every 10 min for 8 hours during sleep in a patient with Nelson's syndrome. The plasma ACTH concentrations were relatively stable, fluctuating in a narrow range. It is strongly suggested that the pituitary tumor itself was secreting ACTH in an autonomous manner and it is concluded that a neuronally initiated program of ACTH secretion, was absent in the present patient with Nelson's syndrome.", "contents": "ACTH secretion during sleep in a patient with Nelson's syndrome. Plasma ACTH determinations were made by radioimmunoassay, every 10 min for 8 hours during sleep in a patient with Nelson's syndrome. The plasma ACTH concentrations were relatively stable, fluctuating in a narrow range. It is strongly suggested that the pituitary tumor itself was secreting ACTH in an autonomous manner and it is concluded that a neuronally initiated program of ACTH secretion, was absent in the present patient with Nelson's syndrome."} {"id": "PMID:172323", "title": "Alteration of thyroidal responsiveness to TSH under the influence of circulating thyroid hormone: short feed-back regulatory effect.", "content": "In order to examine the hypothesis that the thyroidal responsiveness to TSH is under the influence of thyroid hormone, following the T3 injection to the mice, serum T3 concentrations and the response of thyroid tissue to a fixed dose of TSH in terms of intracellular colloid droplet formation was studied. The colloid droplets induced by TSH was significantly reduced when serum T3 was decreasing, while it was significantly increased when serum T3 was increasing. This results demonstrate for the first time the existence of short feed-back loop regulating intra-thyroidal function by circulating T3. To delineate the possible mechanism of action of T3, the thyroid gland of mouse whose serum T3 concentration was elevated by injecting 50 mug T3, was incubated with TSH in vitro. TSH-induced cyclic AMP generation was not inhibited at all but colloid droplet formation was significantly inhibited in the thyroid tissue of the animal whose serum T3 concentration was enormously high. Thus, it was demonstrated that the site at which T3 affects is beyond cylcic AMP generation but prior to endocytosis, being consistent with our previous results.", "contents": "Alteration of thyroidal responsiveness to TSH under the influence of circulating thyroid hormone: short feed-back regulatory effect. In order to examine the hypothesis that the thyroidal responsiveness to TSH is under the influence of thyroid hormone, following the T3 injection to the mice, serum T3 concentrations and the response of thyroid tissue to a fixed dose of TSH in terms of intracellular colloid droplet formation was studied. The colloid droplets induced by TSH was significantly reduced when serum T3 was decreasing, while it was significantly increased when serum T3 was increasing. This results demonstrate for the first time the existence of short feed-back loop regulating intra-thyroidal function by circulating T3. To delineate the possible mechanism of action of T3, the thyroid gland of mouse whose serum T3 concentration was elevated by injecting 50 mug T3, was incubated with TSH in vitro. TSH-induced cyclic AMP generation was not inhibited at all but colloid droplet formation was significantly inhibited in the thyroid tissue of the animal whose serum T3 concentration was enormously high. Thus, it was demonstrated that the site at which T3 affects is beyond cylcic AMP generation but prior to endocytosis, being consistent with our previous results."} {"id": "PMID:172328", "title": "Incorporation rate of glucose carbon, palmitate carbon and leucine carbon into metabolites in relation to enzyme activities and RNA levels in human skeletal muscles.", "content": "The activities (Vmax) of hexokinase, glycogen phosphorylase, glucose-6-phosphate dehydrogenase, phosphofructokinase, lactate dehydrogenase, citrate synthase, cytochrome c oxidase, and 3-OH-acyl-CoA dehydrogenase in human skeletal muscles were compared with the in vitro utilization of glucose and palmitic acid assessed under optimal conditions. Statistically significant correlations between substrate fluxes and enzyme activities were found suggesting that the substrate incorporation rate in vitro in some way reflects the capacity of metabolic pathways. The incorporation rate of leucine into muscle proteins was also statistically significantly correlated to the RNA concentration in the muscle tissue. Glycolytic and glycogenolytic enzymes correlated significantly to each other and correlations were also found between aerobic enzymes supporting the validity of constant proportions between certain key enzymes in human skeletal muscles.", "contents": "Incorporation rate of glucose carbon, palmitate carbon and leucine carbon into metabolites in relation to enzyme activities and RNA levels in human skeletal muscles. The activities (Vmax) of hexokinase, glycogen phosphorylase, glucose-6-phosphate dehydrogenase, phosphofructokinase, lactate dehydrogenase, citrate synthase, cytochrome c oxidase, and 3-OH-acyl-CoA dehydrogenase in human skeletal muscles were compared with the in vitro utilization of glucose and palmitic acid assessed under optimal conditions. Statistically significant correlations between substrate fluxes and enzyme activities were found suggesting that the substrate incorporation rate in vitro in some way reflects the capacity of metabolic pathways. The incorporation rate of leucine into muscle proteins was also statistically significantly correlated to the RNA concentration in the muscle tissue. Glycolytic and glycogenolytic enzymes correlated significantly to each other and correlations were also found between aerobic enzymes supporting the validity of constant proportions between certain key enzymes in human skeletal muscles."} {"id": "PMID:172329", "title": "Adenyl cyclase and cyclic nucleotide phosphodiesterase activities in murine muscular dystrophy.", "content": "Adenyl cyclase and cyclic nucleotide phosphodiesterase activities were assayed in homogenates of hind leg skeletal muscle from dystrophic and normal mice. Adenyl cyclase activity was stimulated 2.5 times by epinephrine and 6 times by fluoride over the basal activity in both dystrophic and normal mice. The activity of adenyl cyclase from dystrophic muscle of mice was significantly higher than that of normal mice under all the conditions tested (i.e. basal, epinephrine and fluoride). Cyclic nucleotide phosphodiesterase from skeletal muscle of mice has two Km's (2.1 and 11 mumol/l) which suggests the existence of either two forms of enzyme or a single enzyme with negative cooperativity. The activity of this enzyme was significantly elevated in the skeletal muscle of dystrophic mice compared to the normal controls. The available evidence suggests that the same cyclic nucleotide phosphodiesterase is responsible for the hydrolysis of both cyclic AMP and cyclic GMP.", "contents": "Adenyl cyclase and cyclic nucleotide phosphodiesterase activities in murine muscular dystrophy. Adenyl cyclase and cyclic nucleotide phosphodiesterase activities were assayed in homogenates of hind leg skeletal muscle from dystrophic and normal mice. Adenyl cyclase activity was stimulated 2.5 times by epinephrine and 6 times by fluoride over the basal activity in both dystrophic and normal mice. The activity of adenyl cyclase from dystrophic muscle of mice was significantly higher than that of normal mice under all the conditions tested (i.e. basal, epinephrine and fluoride). Cyclic nucleotide phosphodiesterase from skeletal muscle of mice has two Km's (2.1 and 11 mumol/l) which suggests the existence of either two forms of enzyme or a single enzyme with negative cooperativity. The activity of this enzyme was significantly elevated in the skeletal muscle of dystrophic mice compared to the normal controls. The available evidence suggests that the same cyclic nucleotide phosphodiesterase is responsible for the hydrolysis of both cyclic AMP and cyclic GMP."} {"id": "PMID:172330", "title": "Enzyme activities in muscle and connective tissue of M. Vastus lateralis in habitually training and sedentary 33 to 70-year-old men.", "content": "A cross-sectional study was carried out to examine the activities of certain enzymes representing aerobic and anaerobic energy metabolism as well as the biosynthesis of collagen of M. vastus lateralis in 23 male endurance athletes in habitual training, aged 33 to 70 years. 23 sedentary healthy men of corresponding ages were selected for the control group. The mean maximal oxygen uptake of the trained subjects was 53.6 ml-kg--1. min--1 and that of the control subjects 36.3 ml-kg--1. min--1. As compared to the control group the trained subjects had significantly higher values in the muscle malate dehydrogenase, succinate dehydrogenase and prolyl hydroxylase activities, whereas the opposite was true in the activity of lactate dehydrogenase. In hexokinase and creatine phosphokinase no marked differences between the groups were observed. The results showed that endurance training leads to increased activities of oxidative enzymes in the skeletal muscle. The adaptation changes were also observed in old men. The increased activity of prolyl hydroxylase may reflect the general enzymatic adaptation to physical training. A possibility exists that the turnover of muscle collagen in endurance athelets is continuously faster than that in sedentary men of corresponding ages.", "contents": "Enzyme activities in muscle and connective tissue of M. Vastus lateralis in habitually training and sedentary 33 to 70-year-old men. A cross-sectional study was carried out to examine the activities of certain enzymes representing aerobic and anaerobic energy metabolism as well as the biosynthesis of collagen of M. vastus lateralis in 23 male endurance athletes in habitual training, aged 33 to 70 years. 23 sedentary healthy men of corresponding ages were selected for the control group. The mean maximal oxygen uptake of the trained subjects was 53.6 ml-kg--1. min--1 and that of the control subjects 36.3 ml-kg--1. min--1. As compared to the control group the trained subjects had significantly higher values in the muscle malate dehydrogenase, succinate dehydrogenase and prolyl hydroxylase activities, whereas the opposite was true in the activity of lactate dehydrogenase. In hexokinase and creatine phosphokinase no marked differences between the groups were observed. The results showed that endurance training leads to increased activities of oxidative enzymes in the skeletal muscle. The adaptation changes were also observed in old men. The increased activity of prolyl hydroxylase may reflect the general enzymatic adaptation to physical training. A possibility exists that the turnover of muscle collagen in endurance athelets is continuously faster than that in sedentary men of corresponding ages."} {"id": "PMID:172331", "title": "The 3'-amido and 5'-amido analogues of adenosine 3':5'-monophosphate; interaction with cAMP-specific proteins.", "content": "The sensitivity for recognition of adenosine 3:5'-monophosphate (cAMP) by its coordinate proteins towards chemical changes in the six-membered cyclic phosphate ring has been investigated. A comparison of the interaction parameters of the 3' and 5'-amido analogues (I, II) and of unsubstituted cAMP has been made using two different protein kinases and the phosphodiesterase from bovine heart. Binding affinity and the capacity of the amido analogues to stimulate the phosphotransferase activity of the kinases is greatly reeuced relative to cAMP, the 3'-position being more sensitive towards the modification than the 5'-position. The coordinate noncyclic derivatives, 3'-deoxy-3'-amino-5'-AMP (IV) and 5'-deoxy-5'-amino-3'-amp (iii), were also tested. Surprisingly activity towards protein kinases was found to be considerable for the 5'-deoxy-5'-amino-3'-AMP (III), while the 3'-deoxy-3'-amino-5'-AMP (IV) is practically inactive. A possible reason for this is that the noncylic 5'-analogue (III) may be able to assume a cyclic structure maintained by internal salt formation. The phosphodiesterase splits both cyclic amido analogues but with reduced rates compared to that of natural cAMP. Kinetic data obtained from different methods reveal a stronger affinity for the 5'-analogue (I) than the 3'-analogue (II) for the active site, although the reaction rate at saturated substrate concentration is significantly higher with II than with I. The properties of the amido and the noncyclic amino analogues are discussed with available data from chemotaxis of the cellular slime moulds. Furthermore data of the respective methylene cyclic derivatives are used for a more comprehensive comparison. The above is interpreted in terms of the electronic features of the substitutions and of the changes in bond distances or angles upon replacement of O by NH or CH2 in the cyclic phosphate ring (obtained from X-ray work).", "contents": "The 3'-amido and 5'-amido analogues of adenosine 3':5'-monophosphate; interaction with cAMP-specific proteins. The sensitivity for recognition of adenosine 3:5'-monophosphate (cAMP) by its coordinate proteins towards chemical changes in the six-membered cyclic phosphate ring has been investigated. A comparison of the interaction parameters of the 3' and 5'-amido analogues (I, II) and of unsubstituted cAMP has been made using two different protein kinases and the phosphodiesterase from bovine heart. Binding affinity and the capacity of the amido analogues to stimulate the phosphotransferase activity of the kinases is greatly reeuced relative to cAMP, the 3'-position being more sensitive towards the modification than the 5'-position. The coordinate noncyclic derivatives, 3'-deoxy-3'-amino-5'-AMP (IV) and 5'-deoxy-5'-amino-3'-amp (iii), were also tested. Surprisingly activity towards protein kinases was found to be considerable for the 5'-deoxy-5'-amino-3'-AMP (III), while the 3'-deoxy-3'-amino-5'-AMP (IV) is practically inactive. A possible reason for this is that the noncylic 5'-analogue (III) may be able to assume a cyclic structure maintained by internal salt formation. The phosphodiesterase splits both cyclic amido analogues but with reduced rates compared to that of natural cAMP. Kinetic data obtained from different methods reveal a stronger affinity for the 5'-analogue (I) than the 3'-analogue (II) for the active site, although the reaction rate at saturated substrate concentration is significantly higher with II than with I. The properties of the amido and the noncyclic amino analogues are discussed with available data from chemotaxis of the cellular slime moulds. Furthermore data of the respective methylene cyclic derivatives are used for a more comprehensive comparison. The above is interpreted in terms of the electronic features of the substitutions and of the changes in bond distances or angles upon replacement of O by NH or CH2 in the cyclic phosphate ring (obtained from X-ray work)."} {"id": "PMID:172332", "title": "Heterogeneity of enterotoxin-like protein extracted from spores fo Clostridium perfringens type A.", "content": "Enterotoxin-like protein was extracted from spores of three enterotoxin-positive and three enterotoxin-negative strains of Clostridium perfringens type A by urea/mercaptoethanol, alkaline mercaptoethanol and alkaline dithiothreitol. Disc immunoelectrophoresis demonstrated that three distinct enterotoxin-like proteins could be extracted. In 7% acrylamide gels, type I, type II, and type III enterotoxinlike proteins had relative mobilities of 0.52, 0.63, and 0.73 respectively. In contrast to disc immunoelectrophoresis, immunoelectrophoresis in agar gel demonstrated identical electrophoretic properties for the various entertoxin-like proteins. Immunoelectrofocusing experiments gave isoelectric points of 4.43, 4.43, 4.36, and 4.52 for purified entertoxin and type I, type II, and type III enterotoxin-like proteins respectively. Ferguson plots (i.e., log relative mobility versus acrylamide concentration) yielded nonparallel lines which intersected at a nonsieving concentration of acrylamide indicating that the various species of enterotoxin-like protein differed in size. Estimation of the molecular weight of purified enterotoxin and the three species of enterotoxin-like protein was done by comparing the slopes obtained in Ferguson plots with those obtained using proteins of a known molecular weight. Molecular weights of 38000, 36500, 23000, and 15400 were obtained for purified enterotoxin, type I, type II, and type III enterotoxin-like protein respectively. Collectively, the evidence indicates that fractionation of the different species of enterotoxin-like protein was due primarily to differences in their size, and that different forms of enterotoxin-like protein can be extracted from spores of different strains of C. perfringens type A.", "contents": "Heterogeneity of enterotoxin-like protein extracted from spores fo Clostridium perfringens type A. Enterotoxin-like protein was extracted from spores of three enterotoxin-positive and three enterotoxin-negative strains of Clostridium perfringens type A by urea/mercaptoethanol, alkaline mercaptoethanol and alkaline dithiothreitol. Disc immunoelectrophoresis demonstrated that three distinct enterotoxin-like proteins could be extracted. In 7% acrylamide gels, type I, type II, and type III enterotoxinlike proteins had relative mobilities of 0.52, 0.63, and 0.73 respectively. In contrast to disc immunoelectrophoresis, immunoelectrophoresis in agar gel demonstrated identical electrophoretic properties for the various entertoxin-like proteins. Immunoelectrofocusing experiments gave isoelectric points of 4.43, 4.43, 4.36, and 4.52 for purified entertoxin and type I, type II, and type III enterotoxin-like proteins respectively. Ferguson plots (i.e., log relative mobility versus acrylamide concentration) yielded nonparallel lines which intersected at a nonsieving concentration of acrylamide indicating that the various species of enterotoxin-like protein differed in size. Estimation of the molecular weight of purified enterotoxin and the three species of enterotoxin-like protein was done by comparing the slopes obtained in Ferguson plots with those obtained using proteins of a known molecular weight. Molecular weights of 38000, 36500, 23000, and 15400 were obtained for purified enterotoxin, type I, type II, and type III enterotoxin-like protein respectively. Collectively, the evidence indicates that fractionation of the different species of enterotoxin-like protein was due primarily to differences in their size, and that different forms of enterotoxin-like protein can be extracted from spores of different strains of C. perfringens type A."} {"id": "PMID:172369", "title": "On the mechanism of inhibition of enzyme induction in Escherichia coli by distamycin A.", "content": "The mechanism of the interference of the antiviral antibiotic distamycin A with the bacterial cell has been investigated. Labelled distamycin A is firmly bound by E. coli cells and the binding process does not require metabolic energy as indicated by the use of inhibitors. The antibiotic does not induce gross alteration in the cell membrane but inhibits cyclic AMP accumulation in the cells exposed to a glucose-free medium. This inhibition is concomitant with that exerted on the synthesis of an inducible enzyme such as beta-galactosidase. By the method of pulse induction it appears that distamycin A exterts its inhibiting effect on inducible synthesis at the level of transcription. This effect is probably related to an interference with the positive control of enzyme synthesis performed via the system represented by cyclic AMP and the CRP protein.", "contents": "On the mechanism of inhibition of enzyme induction in Escherichia coli by distamycin A. The mechanism of the interference of the antiviral antibiotic distamycin A with the bacterial cell has been investigated. Labelled distamycin A is firmly bound by E. coli cells and the binding process does not require metabolic energy as indicated by the use of inhibitors. The antibiotic does not induce gross alteration in the cell membrane but inhibits cyclic AMP accumulation in the cells exposed to a glucose-free medium. This inhibition is concomitant with that exerted on the synthesis of an inducible enzyme such as beta-galactosidase. By the method of pulse induction it appears that distamycin A exterts its inhibiting effect on inducible synthesis at the level of transcription. This effect is probably related to an interference with the positive control of enzyme synthesis performed via the system represented by cyclic AMP and the CRP protein."} {"id": "PMID:172370", "title": "[Synthesis and properties of semisynthetic penicillins containing the furoxan nucleus].", "content": "Synthesis, antibacterial activity and stability in acid solution of potassium salts of 6-(3-methyl-4-furoxancarboxyamido)penicillanic acid and 6-(4-methyl-3-furoxancarboxyamido)penicillanic acid are reported.", "contents": "[Synthesis and properties of semisynthetic penicillins containing the furoxan nucleus]. Synthesis, antibacterial activity and stability in acid solution of potassium salts of 6-(3-methyl-4-furoxancarboxyamido)penicillanic acid and 6-(4-methyl-3-furoxancarboxyamido)penicillanic acid are reported."} {"id": "PMID:172371", "title": "Quantification of triglyceride transport in blood plasma: a critical analysis.", "content": "Reliable and precise quantification of endogenous triglyceride transport in man has not been possible with simple means to date. Direct measurement of net splanchnic secretion of triglyceride fatty acids (TGFA) in very low density lipoproteins (VLDL) provides the must unambiguous information, but precision is low. Coupling infusion of labeled fatty acid with sampling of arterial and hepatic venous blood increases precision; however, the contribution of precursors other than plasma free fatty acids (FFA) must be assessed. Measurement of the rate of hydrolysis of plasma triglycerides after displacing lipases into the blood with heparin holds promise as a simple, nonisotopic method, but it has not been carefully validated and heparin itself alters FFA and triglyceride transport. Multicompartmental analysis following pulse injection of labeled fatty acid offers a practical approach, but uncertainties about the number and location of interacting compartments have made it impossible to determine an absolute value for transport. Reinjection of biologically labeled plasma VLDL is impractical for large scale use, and validity of this approach remains uncertain because of heterogeneity of VLDL-triglycerides and their complex metabolic behavior. Methods to label VLDL-triglycerides in vitro deserve more study as does labeling of other components, such as the B-apoprotein. Such approaches will require rigorous comparison with biologically labeled material as well as careful assessment of alterations in kinetic behavior that may occur when VLDL are separated from blood plasma.", "contents": "Quantification of triglyceride transport in blood plasma: a critical analysis. Reliable and precise quantification of endogenous triglyceride transport in man has not been possible with simple means to date. Direct measurement of net splanchnic secretion of triglyceride fatty acids (TGFA) in very low density lipoproteins (VLDL) provides the must unambiguous information, but precision is low. Coupling infusion of labeled fatty acid with sampling of arterial and hepatic venous blood increases precision; however, the contribution of precursors other than plasma free fatty acids (FFA) must be assessed. Measurement of the rate of hydrolysis of plasma triglycerides after displacing lipases into the blood with heparin holds promise as a simple, nonisotopic method, but it has not been carefully validated and heparin itself alters FFA and triglyceride transport. Multicompartmental analysis following pulse injection of labeled fatty acid offers a practical approach, but uncertainties about the number and location of interacting compartments have made it impossible to determine an absolute value for transport. Reinjection of biologically labeled plasma VLDL is impractical for large scale use, and validity of this approach remains uncertain because of heterogeneity of VLDL-triglycerides and their complex metabolic behavior. Methods to label VLDL-triglycerides in vitro deserve more study as does labeling of other components, such as the B-apoprotein. Such approaches will require rigorous comparison with biologically labeled material as well as careful assessment of alterations in kinetic behavior that may occur when VLDL are separated from blood plasma."} {"id": "PMID:172372", "title": "Triglyceride turnover: a comparison of simultaneous determinations using the radioglyceride and the lipolytic rate procedures.", "content": "Two different methods of examining triglyceride turnover are described. One measures the clearance of endogenously labeled triglyceride glycerol, the radioglyceride method. The other assesses the hydrolysis of endogenous very low density lipoproteins after a primed infusion of maximal doses of heparin, the lipolytic rate. Both depend on widely different assumptions. A comparison of data obtained by both methods at the same time in single individuals with widely differing triglyceride concentrations revealed them to agree quite closely. This correspondence indirectly suggests the validity of the procedures. The procedures have been applied to show that fat-free high-carbohydrate diets accelerate triglyceride production in some humans.", "contents": "Triglyceride turnover: a comparison of simultaneous determinations using the radioglyceride and the lipolytic rate procedures. Two different methods of examining triglyceride turnover are described. One measures the clearance of endogenously labeled triglyceride glycerol, the radioglyceride method. The other assesses the hydrolysis of endogenous very low density lipoproteins after a primed infusion of maximal doses of heparin, the lipolytic rate. Both depend on widely different assumptions. A comparison of data obtained by both methods at the same time in single individuals with widely differing triglyceride concentrations revealed them to agree quite closely. This correspondence indirectly suggests the validity of the procedures. The procedures have been applied to show that fat-free high-carbohydrate diets accelerate triglyceride production in some humans."} {"id": "PMID:172373", "title": "Preliminary model for human lipoprotein metabolism in hyperlipoproteinemia.", "content": "A model is proposed for the metabolism of plasma lipoprotein apoproteins based on studies of a hyperlipoproteinemic subject who received 2.5 mCi[3H]leucine intravenously. Measurements included apoprotein specific activities (apo-B and apo-C) of very low density lipoprotein (VLDL) and of three low density lipoprotein (LDL) subspecies, Sf 17 LDL, Sf 10 LDL, and Sf 4 LDL. Activities of plasma albumin were also determined. The data were analyzed using a compartmental model and the SAAM computer program. A chain-like series of compartments were necessary to simulate plasma VLDL kinetics, suggesting a multistep delipidation process. The data are consistent with the notion that VLDL is the dominant LDL precursor. Two modes of conversion from VLDL to LDL are required. After partial delipidation some VLDL is converted to the Sf 17 LDL, while the remainder undergoes further delipidation before being converted to Sf 4 LDL, the major plasma LDL component. Some direct release of LDL into plasma had to be introduced to fit the data, about 24% of total LDL production. The three LDL subspecies follow a precursor-product relationship (Sf 17 leads to Sf 10 leads to Sf 4). The analysis also indicates that in using labeled leucine as a tracer, the slow exchange of leucine with the total body protein pool must be considered in trying to resolve the LDL subsystem and in the estimation of steady-state apoprotein levels. In view of the fact that the proposed model is based predominantly on the data from a single patient, no generalizations can be made about parameter values. The study is most valuable, however, in pointing out metabolic pathways not considered before and in calling attention to variables that must be considered in the design of experiments to study lipoprotein kinetics.", "contents": "Preliminary model for human lipoprotein metabolism in hyperlipoproteinemia. A model is proposed for the metabolism of plasma lipoprotein apoproteins based on studies of a hyperlipoproteinemic subject who received 2.5 mCi[3H]leucine intravenously. Measurements included apoprotein specific activities (apo-B and apo-C) of very low density lipoprotein (VLDL) and of three low density lipoprotein (LDL) subspecies, Sf 17 LDL, Sf 10 LDL, and Sf 4 LDL. Activities of plasma albumin were also determined. The data were analyzed using a compartmental model and the SAAM computer program. A chain-like series of compartments were necessary to simulate plasma VLDL kinetics, suggesting a multistep delipidation process. The data are consistent with the notion that VLDL is the dominant LDL precursor. Two modes of conversion from VLDL to LDL are required. After partial delipidation some VLDL is converted to the Sf 17 LDL, while the remainder undergoes further delipidation before being converted to Sf 4 LDL, the major plasma LDL component. Some direct release of LDL into plasma had to be introduced to fit the data, about 24% of total LDL production. The three LDL subspecies follow a precursor-product relationship (Sf 17 leads to Sf 10 leads to Sf 4). The analysis also indicates that in using labeled leucine as a tracer, the slow exchange of leucine with the total body protein pool must be considered in trying to resolve the LDL subsystem and in the estimation of steady-state apoprotein levels. In view of the fact that the proposed model is based predominantly on the data from a single patient, no generalizations can be made about parameter values. The study is most valuable, however, in pointing out metabolic pathways not considered before and in calling attention to variables that must be considered in the design of experiments to study lipoprotein kinetics."} {"id": "PMID:172374", "title": "Erythropoietin and the differentiation of red blood cells.", "content": "Erythropoietin is the primary factor regulating red blood cell formation in mammals and some other animals. It has been purified from plasma derived from anemic sheep and from the urine of anemic patients and is a glycoprotein. The sheep hormone has a molecular weight of 46,000 and appears to consist of a single chain. The carbohydrate and amino acid compositions where known, are summarized, as are the known structural requirements for biological activity. Its mode of action as the inducer of red cell differentiation has been studied in marrow cell and fetal liver cell cultures. Erythropoietin interacts first with a protein receptor on its target cell causing the appearance of a cytoplasmic protein thought to be a mediator that, in turn, causes an increased rate of transcription in the target cell nuclei. There are several different species of RNA synthesized before the cells initiate hemoglobin synthesis. The effect on transcription is only indirectly dependent on DNA synthesis. Some properties of the primitive erythropoietin-responsive cell are discussed and a cellular model for blood cell differentiation is presented.", "contents": "Erythropoietin and the differentiation of red blood cells. Erythropoietin is the primary factor regulating red blood cell formation in mammals and some other animals. It has been purified from plasma derived from anemic sheep and from the urine of anemic patients and is a glycoprotein. The sheep hormone has a molecular weight of 46,000 and appears to consist of a single chain. The carbohydrate and amino acid compositions where known, are summarized, as are the known structural requirements for biological activity. Its mode of action as the inducer of red cell differentiation has been studied in marrow cell and fetal liver cell cultures. Erythropoietin interacts first with a protein receptor on its target cell causing the appearance of a cytoplasmic protein thought to be a mediator that, in turn, causes an increased rate of transcription in the target cell nuclei. There are several different species of RNA synthesized before the cells initiate hemoglobin synthesis. The effect on transcription is only indirectly dependent on DNA synthesis. Some properties of the primitive erythropoietin-responsive cell are discussed and a cellular model for blood cell differentiation is presented."} {"id": "PMID:172376", "title": "The expression of avian gs antigen in mammalian Rous sarcoma virus-transformed cells after treatment with 5-iododeoxyuridine and dexamethasone.", "content": "The content of avian gs antigen in RSV-transformed rat cells LW13-RsK1 and LW13-RsK4 showed a transient increase after treatment with 5-iododeoxyuridine. Higher levels of gs antigen were found when treated cells were cultivated in the presence of dexamethasone. In no case was the production of RSV found in treated RSV-transformed rat cell lines when, in addition, XC cells were tested.", "contents": "The expression of avian gs antigen in mammalian Rous sarcoma virus-transformed cells after treatment with 5-iododeoxyuridine and dexamethasone. The content of avian gs antigen in RSV-transformed rat cells LW13-RsK1 and LW13-RsK4 showed a transient increase after treatment with 5-iododeoxyuridine. Higher levels of gs antigen were found when treated cells were cultivated in the presence of dexamethasone. In no case was the production of RSV found in treated RSV-transformed rat cell lines when, in addition, XC cells were tested."} {"id": "PMID:172377", "title": "Effect of prophylactic and therapeutic administration of BCG vaccine on growth of experimental sarcoma.", "content": "The effect of prophylactic and therapeutic administration of BCG vaccine on growth of transplantable sarcomas induced by MSV-Harvey (MSVT1) and 3-methylcholanthrene (MC 11 and MC 12) in C57BL/10Sn mice was studied. Growth of MSVT1 sarcomas was not inhibited by oral or intratumoral BCG therapy. Nor was prophylactic oral administration of BCG followed by therapeutic oral BCG treatment effective. On the other hand, intradermal administration of an adequate dose of BCG vaccine preceding the tumour transplantation inhibited tumour growth. The low (0.05-0.2 mg.) doses of BCG induced resistance comparable to the effect of subcutaneous immunization with tumour cells, whereas the higher (0.5-1.0 mg) doses had no effect. Growth of MC 11 and MC 12 tumours was not affected by prophylactic intradermal BCG administration.", "contents": "Effect of prophylactic and therapeutic administration of BCG vaccine on growth of experimental sarcoma. The effect of prophylactic and therapeutic administration of BCG vaccine on growth of transplantable sarcomas induced by MSV-Harvey (MSVT1) and 3-methylcholanthrene (MC 11 and MC 12) in C57BL/10Sn mice was studied. Growth of MSVT1 sarcomas was not inhibited by oral or intratumoral BCG therapy. Nor was prophylactic oral administration of BCG followed by therapeutic oral BCG treatment effective. On the other hand, intradermal administration of an adequate dose of BCG vaccine preceding the tumour transplantation inhibited tumour growth. The low (0.05-0.2 mg.) doses of BCG induced resistance comparable to the effect of subcutaneous immunization with tumour cells, whereas the higher (0.5-1.0 mg) doses had no effect. Growth of MC 11 and MC 12 tumours was not affected by prophylactic intradermal BCG administration."} {"id": "PMID:172378", "title": "Long-term preservation of transfecting activity of DNA isolated from rat virogenic XC cells transformed by Prague strain of Rous sarcoma virus.", "content": "The DNA isolated from rat virogenic XC cells transformed by Rous sarcoma virus retains standard transfecting activity for 7 months when the DNA solution in 0.1 X PBS, containing 10% glycerol is stored at -70 degrees C. The value of the sedimentation constant S20w does not significantly change during storage.", "contents": "Long-term preservation of transfecting activity of DNA isolated from rat virogenic XC cells transformed by Prague strain of Rous sarcoma virus. The DNA isolated from rat virogenic XC cells transformed by Rous sarcoma virus retains standard transfecting activity for 7 months when the DNA solution in 0.1 X PBS, containing 10% glycerol is stored at -70 degrees C. The value of the sedimentation constant S20w does not significantly change during storage."} {"id": "PMID:172379", "title": "Mode of dermal-epidermal adhesion.", "content": "The mode of dermal-epidermal adhesion was investigated by a systematic enzyme digestion of the dermo-epidermal junction. The anchoring fibrils and filaments were found to consist of elastin and collagen-like filaments which intertwine to form the adepidermal membrane. A model on the possible in situ conditions is proposed.", "contents": "Mode of dermal-epidermal adhesion. The mode of dermal-epidermal adhesion was investigated by a systematic enzyme digestion of the dermo-epidermal junction. The anchoring fibrils and filaments were found to consist of elastin and collagen-like filaments which intertwine to form the adepidermal membrane. A model on the possible in situ conditions is proposed."} {"id": "PMID:172391", "title": "Mechanism of nucleotide inhibition of gonadotropin binding to cell membranes of bovine corpus luteum.", "content": "ATP, CTP, ADP, AMP, cyclic 3',5'-AMP (cAMP) and cyclic 3',5'-CMP (cCMP) effectively inhibited the specific binding of 125I-labelled human chorionic gonadotropin ([125I]HCG) to bovine corpus luteum cell membranes. This inhibition was observed with 2.5 X 10(-4) M to 1.0 X 10(-3) M nucleotide concentrations, regardless of the presence of a nucleotide regenerating system. Submaximal concentrations of combinations of the nucleotides were additive in inhibiting binding. The inhibition of [125I]HCG binding was observed when the nucleotides were added at the beginning of or during incubation or preincubation of the membranes with nucleotides. Preincubation of membranes with CTP and cAMP, subsequent washing and reincubation with hormone, showed time-dependent inhibition of [125I]HCG binding when the preincubation temperature was 38 degrees C but not at 4 degrees C. The concentrated supernates from nucleotides preincubated with membranes had no inhibitory effect on [125I]HCG binding to fresh membranes. In the absence of added nucleotides, [125I]HCG-membrane interaction had the following apparent binding constants: a Kd of 1.5 X 10(-10) M, 46.3 fmoles of binding sites per mg membrane protein, and rate constants for association and dissociation 4.0 X 10(6) M-1 sec-1 and 1.0 X 10(-3) sec-1, respectively. At steady state conditions of [125I]HCG binding, CTP inhibited [125I]HCG at lower concentrations of added hormone (less than 3 X 10(-9) M) whereas at higher concentrations, this nucleotide enhanced [125I]HCG binding. Scatchard analysis of the data revealed that inhibition and enhancement of [125I]HCG binding in the presence of CTP were due to lowered affinity of gonadotropin receptors (32-37) fold) and to exposure of new low-affinity binding sites for [125I]HCG, respectively. At non-steady-state conditions, nucleotides increased dissociation rates (80 to 100%) and decreased association rates (30 to 38%). The data appear to be compatible with the suggestion that the nucleotides may bind to sites in the membranes and subsequently induce conformational changes in membrane components, resulting in a decreased affinity of gonadotropin receptors. The physiological significance of these findings needs to be determined.", "contents": "Mechanism of nucleotide inhibition of gonadotropin binding to cell membranes of bovine corpus luteum. ATP, CTP, ADP, AMP, cyclic 3',5'-AMP (cAMP) and cyclic 3',5'-CMP (cCMP) effectively inhibited the specific binding of 125I-labelled human chorionic gonadotropin ([125I]HCG) to bovine corpus luteum cell membranes. This inhibition was observed with 2.5 X 10(-4) M to 1.0 X 10(-3) M nucleotide concentrations, regardless of the presence of a nucleotide regenerating system. Submaximal concentrations of combinations of the nucleotides were additive in inhibiting binding. The inhibition of [125I]HCG binding was observed when the nucleotides were added at the beginning of or during incubation or preincubation of the membranes with nucleotides. Preincubation of membranes with CTP and cAMP, subsequent washing and reincubation with hormone, showed time-dependent inhibition of [125I]HCG binding when the preincubation temperature was 38 degrees C but not at 4 degrees C. The concentrated supernates from nucleotides preincubated with membranes had no inhibitory effect on [125I]HCG binding to fresh membranes. In the absence of added nucleotides, [125I]HCG-membrane interaction had the following apparent binding constants: a Kd of 1.5 X 10(-10) M, 46.3 fmoles of binding sites per mg membrane protein, and rate constants for association and dissociation 4.0 X 10(6) M-1 sec-1 and 1.0 X 10(-3) sec-1, respectively. At steady state conditions of [125I]HCG binding, CTP inhibited [125I]HCG at lower concentrations of added hormone (less than 3 X 10(-9) M) whereas at higher concentrations, this nucleotide enhanced [125I]HCG binding. Scatchard analysis of the data revealed that inhibition and enhancement of [125I]HCG binding in the presence of CTP were due to lowered affinity of gonadotropin receptors (32-37) fold) and to exposure of new low-affinity binding sites for [125I]HCG, respectively. At non-steady-state conditions, nucleotides increased dissociation rates (80 to 100%) and decreased association rates (30 to 38%). The data appear to be compatible with the suggestion that the nucleotides may bind to sites in the membranes and subsequently induce conformational changes in membrane components, resulting in a decreased affinity of gonadotropin receptors. The physiological significance of these findings needs to be determined."} {"id": "PMID:172392", "title": "Cyclic nucleotide phosphodiesterases in uterine development.", "content": "Activities of cyclic nucleotide phosphodiesterase were studied in rat uterus as a function of age, DNA and protein content. Linear kinetics were observed for uterine homogenate cyclic GMP (cGMP) phosphodiesterase activity, but anomalous double-reciprocal plots, suggestive of multiple enzyme forms, were observed for cyclic AMP (cAMP) hydrolysis, cAMP phosphodiesterase was therefore measured at high and low substrate concentrations, 200 muM and 0.25 muM cAMP, respectively, to approximate multiple enzyme activities. Based upon total organ content, the total cAMP and cGMP phosphodiesterase activities increased throughout uterine development, from 5-50 days of age. On the same basis, the apparent low KM cAMP phosphodiesterase increased only between days 5 and 15 and showed no significant increase between days 15 and 50. On the other hand, specific activities of an apparent low KM cAMP phosphodiesterase, expressed per mg of protein or per mug of DNA, showed a marked reduction in activity between 30 and 50 days of age. Chronic administration of 17beta-estradiol to immature rats increased their uterine protein content and decreased the specific activity of the apparent low KM cAMP phosphodiesterase. In another estrogen target tissue, the anterior pituitary, protein and DNA content also increased during development but no changes in specific activities of cyclic nucleotide phosphodiesterase were noted. These results suggest the possible participation of cyclic nucleotide phosphodiesterases in the induction of uterine growth and development by ovarian hormones.", "contents": "Cyclic nucleotide phosphodiesterases in uterine development. Activities of cyclic nucleotide phosphodiesterase were studied in rat uterus as a function of age, DNA and protein content. Linear kinetics were observed for uterine homogenate cyclic GMP (cGMP) phosphodiesterase activity, but anomalous double-reciprocal plots, suggestive of multiple enzyme forms, were observed for cyclic AMP (cAMP) hydrolysis, cAMP phosphodiesterase was therefore measured at high and low substrate concentrations, 200 muM and 0.25 muM cAMP, respectively, to approximate multiple enzyme activities. Based upon total organ content, the total cAMP and cGMP phosphodiesterase activities increased throughout uterine development, from 5-50 days of age. On the same basis, the apparent low KM cAMP phosphodiesterase increased only between days 5 and 15 and showed no significant increase between days 15 and 50. On the other hand, specific activities of an apparent low KM cAMP phosphodiesterase, expressed per mg of protein or per mug of DNA, showed a marked reduction in activity between 30 and 50 days of age. Chronic administration of 17beta-estradiol to immature rats increased their uterine protein content and decreased the specific activity of the apparent low KM cAMP phosphodiesterase. In another estrogen target tissue, the anterior pituitary, protein and DNA content also increased during development but no changes in specific activities of cyclic nucleotide phosphodiesterase were noted. These results suggest the possible participation of cyclic nucleotide phosphodiesterases in the induction of uterine growth and development by ovarian hormones."} {"id": "PMID:172393", "title": "Effect of partially purified NSILA on adenylate cyclase, phosphodiesterase and 3',5'-cyclic AMP in fat cells.", "content": "Partially purified, non-suppressible, insulin-like material (NSILA-S) was studied with respect to its effect on the levels of 3',5'-cyclic adenosine monophosphate (cAMP) and its mechanism of action in the control of this nucleotide in rat fat cells. NSILA-S prevents the rise of cAMP in fat cells under the influence of isoproterenol with similar kinetics to insulin. A maximal effect is observed at about 70 ng/ml with a biological activity equivalent to 200 muU/ml of insulin. NSILA-S inhibits norepinephrine-stimulated adenylate cyclase activity in fat cell ghosts and partially purified plasma membrane preparations. At 10 mM Mg2+, the inhibition is characterized by an effect of Vmax without change in affinity towards ATP (apparent KM 30 muM). Similarly there is no observed change in affinity towards Mg2+. With respect to inhibition of norepinephrine-stimulated adenylate cyclase, the dose-response curve of NSILA-S is similar to that already found with intact cells. The effect of norepinephrine is inhibited throughout the dose-response range between 5 X 10(-7) and 5 X 10(-4) M. In contrast to previous observations with insulin in ghosts, NSILA-S inhibits the basal adenylate cyclase activity. Cyclic nucleotide phosphodiesterase activity in homogenates as measured at 1.0 muM substrate is increased by 90% after previous incubation of fat cells with NSILA-S. The study suggests that the anti-lipolytic effect of NSILA-S is mediated by a lowering of cAMP through inhibition of the adenylate cyclase and/or stimulation of the phosphodiesterase system.", "contents": "Effect of partially purified NSILA on adenylate cyclase, phosphodiesterase and 3',5'-cyclic AMP in fat cells. Partially purified, non-suppressible, insulin-like material (NSILA-S) was studied with respect to its effect on the levels of 3',5'-cyclic adenosine monophosphate (cAMP) and its mechanism of action in the control of this nucleotide in rat fat cells. NSILA-S prevents the rise of cAMP in fat cells under the influence of isoproterenol with similar kinetics to insulin. A maximal effect is observed at about 70 ng/ml with a biological activity equivalent to 200 muU/ml of insulin. NSILA-S inhibits norepinephrine-stimulated adenylate cyclase activity in fat cell ghosts and partially purified plasma membrane preparations. At 10 mM Mg2+, the inhibition is characterized by an effect of Vmax without change in affinity towards ATP (apparent KM 30 muM). Similarly there is no observed change in affinity towards Mg2+. With respect to inhibition of norepinephrine-stimulated adenylate cyclase, the dose-response curve of NSILA-S is similar to that already found with intact cells. The effect of norepinephrine is inhibited throughout the dose-response range between 5 X 10(-7) and 5 X 10(-4) M. In contrast to previous observations with insulin in ghosts, NSILA-S inhibits the basal adenylate cyclase activity. Cyclic nucleotide phosphodiesterase activity in homogenates as measured at 1.0 muM substrate is increased by 90% after previous incubation of fat cells with NSILA-S. The study suggests that the anti-lipolytic effect of NSILA-S is mediated by a lowering of cAMP through inhibition of the adenylate cyclase and/or stimulation of the phosphodiesterase system."} {"id": "PMID:172394", "title": "Studies on isolated rat adrenal cells metabolism of hydroxylated sterols.", "content": "Corticosterone production by isolated rat adrenal cells in the absence of ACTH is stimulated by 20alpha-hydroxycholesterol, 22R-hydroxycholesterol and 25-hydroxycholesterol. This effect is also seen at sub-maximal ACTH concentrations. Aminoglutethimide (AGI) inhibits the stimulation caused by the three hydroxylated cholesterols. In the presence of ACTH, AGI also inhibits steroid production both under control conditions and in the presence of the sterols. The stimulation by 25-hydroxycholesterol is dose-dependent, both in the presence and absence of a sub-maximal ACTH concentration. At maximal ACTH concentrations 25-hydroxycholesterol does not give additional stimulation. Cycloheximide has no effect on corticosterone production from 25-hydroxycholesterol whether ACTH is present or not. Our results indicate that 25-hydroxycholesterol is a good substrate for the study of the cholesterol side-chain cleaving system and the mechanism of action of ACTH at the levels of the intact cell.", "contents": "Studies on isolated rat adrenal cells metabolism of hydroxylated sterols. Corticosterone production by isolated rat adrenal cells in the absence of ACTH is stimulated by 20alpha-hydroxycholesterol, 22R-hydroxycholesterol and 25-hydroxycholesterol. This effect is also seen at sub-maximal ACTH concentrations. Aminoglutethimide (AGI) inhibits the stimulation caused by the three hydroxylated cholesterols. In the presence of ACTH, AGI also inhibits steroid production both under control conditions and in the presence of the sterols. The stimulation by 25-hydroxycholesterol is dose-dependent, both in the presence and absence of a sub-maximal ACTH concentration. At maximal ACTH concentrations 25-hydroxycholesterol does not give additional stimulation. Cycloheximide has no effect on corticosterone production from 25-hydroxycholesterol whether ACTH is present or not. Our results indicate that 25-hydroxycholesterol is a good substrate for the study of the cholesterol side-chain cleaving system and the mechanism of action of ACTH at the levels of the intact cell."} {"id": "PMID:172395", "title": "The estrogen cytosol receptor of female ovine pituitary.", "content": "The biochemical parameters of estrone and estradiol binding to the cytosol fraction of ovine anterior pituitary were investigated. When increasing amounts of [3H]estrone or [3H]estradiol were incubated with the 105,000 g fraction from the pituitary, both hormones bound to a receptor with the same apparent KD (mean +/- S.E., estrone = 1.40 +/- 0.30 X 10(-10) M, estradiol = 1.03 +/- 0.11 X 10(-10)M) and the same concentration of binding sites (estrone = 3.22 +/- 0.58 X 10(-14) moles/mg protein, estradiol = 3.92 +/- 0.19 X 10(-14)). No conversion of [3H]estrone to [3H]estradiol under the experimental conditions used could be demonstrated. The receptor-estrogen complex exhibited identical sedimentation coefficients (7-8 S) with either hormone. The receptor was specific only for estrogens; neither 500-fold excess of testosterone nor progesterone affected binding. Competitive inhibition using increasing amounts of non-radioactive estrone or estradiol with [3H]estrone or [3H]estradiol resulted in parallel displacement of the radioactive hormone. These results strongly suggest that both hormones bind to the same pituitary cytosol receptor.", "contents": "The estrogen cytosol receptor of female ovine pituitary. The biochemical parameters of estrone and estradiol binding to the cytosol fraction of ovine anterior pituitary were investigated. When increasing amounts of [3H]estrone or [3H]estradiol were incubated with the 105,000 g fraction from the pituitary, both hormones bound to a receptor with the same apparent KD (mean +/- S.E., estrone = 1.40 +/- 0.30 X 10(-10) M, estradiol = 1.03 +/- 0.11 X 10(-10)M) and the same concentration of binding sites (estrone = 3.22 +/- 0.58 X 10(-14) moles/mg protein, estradiol = 3.92 +/- 0.19 X 10(-14)). No conversion of [3H]estrone to [3H]estradiol under the experimental conditions used could be demonstrated. The receptor-estrogen complex exhibited identical sedimentation coefficients (7-8 S) with either hormone. The receptor was specific only for estrogens; neither 500-fold excess of testosterone nor progesterone affected binding. Competitive inhibition using increasing amounts of non-radioactive estrone or estradiol with [3H]estrone or [3H]estradiol resulted in parallel displacement of the radioactive hormone. These results strongly suggest that both hormones bind to the same pituitary cytosol receptor."} {"id": "PMID:172397", "title": "Hormonal regulation of glycogen metabolism in human fetal liver. I. Normal development and effects of dibutyryl cyclic AMP, glucagon, and insulin in liver explants.", "content": "Glycogen accumulates in human fetal liver beginning at the eighth week of gestation. A parallel increase in total glycogen synthase activity is found, although the I-form activity remains low and constant throughout the first two thirds of gestation. Total phosphorylase activity increases slightly during this period, with the proportion in the active form amounting to about one half of the total throughout. After an initial rapid decline, the glycogen concentration in explants of human fetal liver remained constant for twenty to forty hours at about 20 per cent of the in vivo level. Incubation with glucagon, cyclic AMP (adenosine 3',5'-monophosphate) or its dibutyryl derivative markedly reduced tissue glycogen concentrations while insulin brought about a small increase. The effect of maximal doses of dibutyryl cyclic AMP and glucagon were the same, and the combination of agents produced no further effect. The response to dibutyryl cyclic AMP was apparent by one hour and maximal by three to six hours, whereas the response to insulin required about six hours to be detected, and it continued for at least eighteen hours. Insulin antagonized the glycogenolytic effect of low doses of glucagon or theophylline but was without significant effect in the presence of high glucagon concentrations. Glucagon stimulated cyclic AMP output from explants, and this effect was further augmented by theophylline. Insultin had no consistent effect on cyclic AMP output in either the presence or the absence of glucagon or theophylline. Incubation with dibutyryl cyclic AMP resulted in a decrease of glycogen synthase I-form activity, while insulin tended to increase this enzyme activity. In neither circumstance was the proportion of active phosphorylase altered. These results suggest that the regulation of glycogen levels in human fetal liver by cyclic AMP, glucagon, and insulin may entail alterations in the activity of glycogen synthase activity without necessitating alterations in phosphorylase activity. Cyclic AMP or glucagon was capable of depleting tissue glycogen stores in tissue from fetuses of six weeks' gestation. Insulin increased tissue glycogen concentrations in tissue from fetuses of seven or more weeks.", "contents": "Hormonal regulation of glycogen metabolism in human fetal liver. I. Normal development and effects of dibutyryl cyclic AMP, glucagon, and insulin in liver explants. Glycogen accumulates in human fetal liver beginning at the eighth week of gestation. A parallel increase in total glycogen synthase activity is found, although the I-form activity remains low and constant throughout the first two thirds of gestation. Total phosphorylase activity increases slightly during this period, with the proportion in the active form amounting to about one half of the total throughout. After an initial rapid decline, the glycogen concentration in explants of human fetal liver remained constant for twenty to forty hours at about 20 per cent of the in vivo level. Incubation with glucagon, cyclic AMP (adenosine 3',5'-monophosphate) or its dibutyryl derivative markedly reduced tissue glycogen concentrations while insulin brought about a small increase. The effect of maximal doses of dibutyryl cyclic AMP and glucagon were the same, and the combination of agents produced no further effect. The response to dibutyryl cyclic AMP was apparent by one hour and maximal by three to six hours, whereas the response to insulin required about six hours to be detected, and it continued for at least eighteen hours. Insulin antagonized the glycogenolytic effect of low doses of glucagon or theophylline but was without significant effect in the presence of high glucagon concentrations. Glucagon stimulated cyclic AMP output from explants, and this effect was further augmented by theophylline. Insultin had no consistent effect on cyclic AMP output in either the presence or the absence of glucagon or theophylline. Incubation with dibutyryl cyclic AMP resulted in a decrease of glycogen synthase I-form activity, while insulin tended to increase this enzyme activity. In neither circumstance was the proportion of active phosphorylase altered. These results suggest that the regulation of glycogen levels in human fetal liver by cyclic AMP, glucagon, and insulin may entail alterations in the activity of glycogen synthase activity without necessitating alterations in phosphorylase activity. Cyclic AMP or glucagon was capable of depleting tissue glycogen stores in tissue from fetuses of six weeks' gestation. Insulin increased tissue glycogen concentrations in tissue from fetuses of seven or more weeks."} {"id": "PMID:172398", "title": "Effect of Shigella enterotoxin on electrolyte transport in rabbit ileum.", "content": "Shigella dysenteriae I is one of several bacteria which produces an enterotoxin capable of stimulating intestinal water and electrolyte secretion. Unlike cholera and Escherichia coli enterotoxins which have been shown to increase intracellular cyclic adenosine monophosphate levels in the small intestine, the mechanism by which shigella enterotoxin causes intestinal secretion is not known. To study shigella enterotoxin-stimulated intestinal secretion, rabbit ileal mucosa exposed in vivo to Shigella dysenteriae I enterotoxin was studied in vitro in a modified Ussing chamber. Fluid and electrolyte accumulation occurred in vivo and net sodium secretion was present in vitro in the enterotoxin-exposed tissue in contrast to net sodium absorption in control mucosa. Short-circuit current (Isc) was similar in shigella enterotoxin-exposed tissue compared with control tissue. The increase adenosine monophosphate was similar to enterotoxin-exposed and control mucosa. The addition of glucose resulted in a smaller increment of Isc in shigella enterotoxin-treated tissue. Mucosal cyclic adenosine monophosphate levels in enterotoxin-exposed mucosa did not differ from those of control. These results indicate that the characteristics of rabbit ileal mucosa exposed to shigella enterotoxin and cholera enterotoxin markedly differ, although both produce electrolyte secretion both in vivo and in vitro. These studies further suggest that, in contrast to its role in cholera enterotoxin-induced intestinal secretion, cyclic adenosine monophosphate may not be in the mediator of shigella enterotoxin stimulation of intestinal fluid and electrolyte secretion.", "contents": "Effect of Shigella enterotoxin on electrolyte transport in rabbit ileum. Shigella dysenteriae I is one of several bacteria which produces an enterotoxin capable of stimulating intestinal water and electrolyte secretion. Unlike cholera and Escherichia coli enterotoxins which have been shown to increase intracellular cyclic adenosine monophosphate levels in the small intestine, the mechanism by which shigella enterotoxin causes intestinal secretion is not known. To study shigella enterotoxin-stimulated intestinal secretion, rabbit ileal mucosa exposed in vivo to Shigella dysenteriae I enterotoxin was studied in vitro in a modified Ussing chamber. Fluid and electrolyte accumulation occurred in vivo and net sodium secretion was present in vitro in the enterotoxin-exposed tissue in contrast to net sodium absorption in control mucosa. Short-circuit current (Isc) was similar in shigella enterotoxin-exposed tissue compared with control tissue. The increase adenosine monophosphate was similar to enterotoxin-exposed and control mucosa. The addition of glucose resulted in a smaller increment of Isc in shigella enterotoxin-treated tissue. Mucosal cyclic adenosine monophosphate levels in enterotoxin-exposed mucosa did not differ from those of control. These results indicate that the characteristics of rabbit ileal mucosa exposed to shigella enterotoxin and cholera enterotoxin markedly differ, although both produce electrolyte secretion both in vivo and in vitro. These studies further suggest that, in contrast to its role in cholera enterotoxin-induced intestinal secretion, cyclic adenosine monophosphate may not be in the mediator of shigella enterotoxin stimulation of intestinal fluid and electrolyte secretion."} {"id": "PMID:172399", "title": "Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin.", "content": "Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.", "contents": "Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin. Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process."} {"id": "PMID:172400", "title": "Etiological spectrum of post-transfusion hepatitis.", "content": "Frequent occurrence of post-transfusion hepatitis continues despite screening for Australia antigen in blood before transfusion and elimination of commercial donor sources. The majority of these cases appears unrelated to hepatitis B virus. Preoperative, acute, and convalescent serra were screened for evidence of hepatitis B, hepatitis A, Epstein-Barr, and cytomegalovirus exposure in 34 cardiac surgery patients developing post-transfusion hepatitis postoperatively. Four patients showed evidence of hepatitis B infection and 3 patients developed significant antibody titer rises to cytomegalovirus. No patient showed evidence for acute hepatitis A infection postoperatively in response to blood transfusions. Epstein-Barr virus was also not responsible for any cases of post-transfusion hepatitis. Presently available laboratory methods failed to implicate hepatitis A, Epstein-Barr, or cytomegalo-virus in the majority of non-B post-transfusion hepatitis cases. This suggests that identification and characterization of additional hepatitis-producing agents will be required to define further the epidemiology of post-transfusion hepatitis and develop measures for its prevention.", "contents": "Etiological spectrum of post-transfusion hepatitis. Frequent occurrence of post-transfusion hepatitis continues despite screening for Australia antigen in blood before transfusion and elimination of commercial donor sources. The majority of these cases appears unrelated to hepatitis B virus. Preoperative, acute, and convalescent serra were screened for evidence of hepatitis B, hepatitis A, Epstein-Barr, and cytomegalovirus exposure in 34 cardiac surgery patients developing post-transfusion hepatitis postoperatively. Four patients showed evidence of hepatitis B infection and 3 patients developed significant antibody titer rises to cytomegalovirus. No patient showed evidence for acute hepatitis A infection postoperatively in response to blood transfusions. Epstein-Barr virus was also not responsible for any cases of post-transfusion hepatitis. Presently available laboratory methods failed to implicate hepatitis A, Epstein-Barr, or cytomegalo-virus in the majority of non-B post-transfusion hepatitis cases. This suggests that identification and characterization of additional hepatitis-producing agents will be required to define further the epidemiology of post-transfusion hepatitis and develop measures for its prevention."} {"id": "PMID:172401", "title": "[Histological and histochemical studies on testis, epididymis and ductus defrens of the rooster (Gallus domesticus)].", "content": "Testis, epididymis and ductus deferens of the adult domestic fowl and male gonads of juvenile roosters have been studied by means of histochemical and histological methods. Testicular interstitial cells: According to enzyme-histochemical results oxidative energy production seems to be of minor importance. An extraordinarily high activity of lysosomal enzymes (acid phosphatase and esterases in the adult, esterases only in the immature) is observed. Positive reactions of 3beta-steroid-dehydrogenase and enzymes of the pentose phosphate cycle indicate steroid hormone production; the pathways of the steroid synthesis, however, are probably different in adult and immature testes. A remarkable LAP content of juvenile Leydig cells is a parameter of an increased protein metabolism. Areas of reserve cells: Focal accumulation of these cell types are observed in testis and epididymis of the immature and in the epididymis of the adult fowl. Reserve cells reveal distinct activities of LAP (prospective growth ability) and 3beta-HstDH (reserve capacity for steriod synthesis). All other enzymes studied react weakly, thus pointing to a generally low metabolic activity. Seminiferous tubules: The strong reaction of alkaline phosphatase in the peritubular cells may play a part in energy disposition for contractions. Sertoli cells of adult animals are rich in lysosomal enzymes and enzymes of the glycolytic chain but oxidoreductases react weaker than in mammalian Sertoli cells. This indicates that nutritive interactions between germ and Sertoli cells in birds are different from those in mammals: The basally orientated germ cells of birds contain strong activities of diaphorases, LDH, SDH, Cyto-Ox and seem to be metabolically rather indipendent from Sertoli cells.", "contents": "[Histological and histochemical studies on testis, epididymis and ductus defrens of the rooster (Gallus domesticus)]. Testis, epididymis and ductus deferens of the adult domestic fowl and male gonads of juvenile roosters have been studied by means of histochemical and histological methods. Testicular interstitial cells: According to enzyme-histochemical results oxidative energy production seems to be of minor importance. An extraordinarily high activity of lysosomal enzymes (acid phosphatase and esterases in the adult, esterases only in the immature) is observed. Positive reactions of 3beta-steroid-dehydrogenase and enzymes of the pentose phosphate cycle indicate steroid hormone production; the pathways of the steroid synthesis, however, are probably different in adult and immature testes. A remarkable LAP content of juvenile Leydig cells is a parameter of an increased protein metabolism. Areas of reserve cells: Focal accumulation of these cell types are observed in testis and epididymis of the immature and in the epididymis of the adult fowl. Reserve cells reveal distinct activities of LAP (prospective growth ability) and 3beta-HstDH (reserve capacity for steriod synthesis). All other enzymes studied react weakly, thus pointing to a generally low metabolic activity. Seminiferous tubules: The strong reaction of alkaline phosphatase in the peritubular cells may play a part in energy disposition for contractions. Sertoli cells of adult animals are rich in lysosomal enzymes and enzymes of the glycolytic chain but oxidoreductases react weaker than in mammalian Sertoli cells. This indicates that nutritive interactions between germ and Sertoli cells in birds are different from those in mammals: The basally orientated germ cells of birds contain strong activities of diaphorases, LDH, SDH, Cyto-Ox and seem to be metabolically rather indipendent from Sertoli cells."} {"id": "PMID:172405", "title": "Immune response and the B blood group locus in chickens.", "content": "Chickens of three blood group genotypes, B1B1, B1B2 and B1B19, were compared in their ability to produce antibodies. The B locus is the major histocompatibility locus in this species. Homozygous B1 pullets had significantly higher adult mortality than did the B1 heterozygotes. In two separate experiments the B1B1 females produced significantly fewer antibodies to Salmonella pullorum than did the B1 heterozygotes. Also the B1B1 pullets responded with lower antibody titers following immunization with ferritin, bovine serum albumin and parainfluenza-3 virus, although the differences were not significant. The results of this study suggest that an immune response gene is associated with the major histocompatibility locus in chickens, paralleling the H-2 locus and Ir genes in mice.", "contents": "Immune response and the B blood group locus in chickens. Chickens of three blood group genotypes, B1B1, B1B2 and B1B19, were compared in their ability to produce antibodies. The B locus is the major histocompatibility locus in this species. Homozygous B1 pullets had significantly higher adult mortality than did the B1 heterozygotes. In two separate experiments the B1B1 females produced significantly fewer antibodies to Salmonella pullorum than did the B1 heterozygotes. Also the B1B1 pullets responded with lower antibody titers following immunization with ferritin, bovine serum albumin and parainfluenza-3 virus, although the differences were not significant. The results of this study suggest that an immune response gene is associated with the major histocompatibility locus in chickens, paralleling the H-2 locus and Ir genes in mice."} {"id": "PMID:172412", "title": "Platelet aggregometry and anti-platelet isoantibodies.", "content": "102 sera from polytransfused patients have been screened in platelet aggregometry. Anti-human platelet isoantibodies, tested against 'responsive' human platelets in PRP, give in the aggregometer a decrease in optical density recorded as a sigmoidal curve. In the first step of reaction PF3 availability suggests that the primary action of antibody is to damage the platelet membrane. The second step might be a true aggregation (an ADP-mediated platelet clumping) or a platelet lysis, depending on the type and the potency of antibody, on the type of platelets (normal or thrombasthenic) and on some experimental conditions. These conclusions, confirmed by electron microscopy findings, suggest that aggregometry is a very rapid and simple method of detecting platelet antibodies.", "contents": "Platelet aggregometry and anti-platelet isoantibodies. 102 sera from polytransfused patients have been screened in platelet aggregometry. Anti-human platelet isoantibodies, tested against 'responsive' human platelets in PRP, give in the aggregometer a decrease in optical density recorded as a sigmoidal curve. In the first step of reaction PF3 availability suggests that the primary action of antibody is to damage the platelet membrane. The second step might be a true aggregation (an ADP-mediated platelet clumping) or a platelet lysis, depending on the type and the potency of antibody, on the type of platelets (normal or thrombasthenic) and on some experimental conditions. These conclusions, confirmed by electron microscopy findings, suggest that aggregometry is a very rapid and simple method of detecting platelet antibodies."} {"id": "PMID:172413", "title": "[Surgical treatment of congenital malformations of the hand].", "content": "The commoner and more important congenital deformities of the hand are reviewed, considering their clinical picture, indications and optimal age for intervention, operative technique, postoperative care, and results. It is stressed that the value of many of the procedures can be assessed only after several years, and often only at the end of the growing period. The following malformations are discussed: 1. Syndactyly: There are many patterns of deformity; fusion of fingers of unequal legnth and distal bony fusion with convergence are absolute indications for early separation (six months of age); in uncomplicated cases operation can wait until the second year of life. Correctly placed skin incisions are of great importance for the prevention of scar contractures; a zig-zag incision forms long triangular flaps for cover of the sides of the fingers, splitting up areas of full-thickness skin graft; the commissure is formed from either two triangular flaps or a single dorsal rectangular flap...", "contents": "[Surgical treatment of congenital malformations of the hand]. The commoner and more important congenital deformities of the hand are reviewed, considering their clinical picture, indications and optimal age for intervention, operative technique, postoperative care, and results. It is stressed that the value of many of the procedures can be assessed only after several years, and often only at the end of the growing period. The following malformations are discussed: 1. Syndactyly: There are many patterns of deformity; fusion of fingers of unequal legnth and distal bony fusion with convergence are absolute indications for early separation (six months of age); in uncomplicated cases operation can wait until the second year of life. Correctly placed skin incisions are of great importance for the prevention of scar contractures; a zig-zag incision forms long triangular flaps for cover of the sides of the fingers, splitting up areas of full-thickness skin graft; the commissure is formed from either two triangular flaps or a single dorsal rectangular flap..."} {"id": "PMID:172414", "title": "[Critical considerations of various surgical methods for correction of the syndactylia (report on an observation period of 10-20 years)].", "content": "During the postoperative period of 10 to 21 years 58 syndactylies in 45 hands of 30 patients were followed-up with special attention to alternations due to growth. These were prevented in the majority of the patients, if the skin cover for the commissure was done by both a dorsal and palmar triangular skin flap and for the side areas of the fingers by several transversely oriented full thickness skin grafts, separated by bridges of the finger skin. In none of the 37 syndactylies in which this procedure was performed, was a corrective operation necessary at the end of the growth period. These results harmonize with previous follow-up studies (MILLESI 1964). The observations of these patients for an additional 10 years have not shown any alterations due to growth.", "contents": "[Critical considerations of various surgical methods for correction of the syndactylia (report on an observation period of 10-20 years)]. During the postoperative period of 10 to 21 years 58 syndactylies in 45 hands of 30 patients were followed-up with special attention to alternations due to growth. These were prevented in the majority of the patients, if the skin cover for the commissure was done by both a dorsal and palmar triangular skin flap and for the side areas of the fingers by several transversely oriented full thickness skin grafts, separated by bridges of the finger skin. In none of the 37 syndactylies in which this procedure was performed, was a corrective operation necessary at the end of the growth period. These results harmonize with previous follow-up studies (MILLESI 1964). The observations of these patients for an additional 10 years have not shown any alterations due to growth."} {"id": "PMID:172415", "title": "Histochemical studies on the albino rat pancreas in different periods following vagotomy and simultaneous pyloromyotomy.", "content": "The effect of complete subphrenic vagotomy and simultaneous pyloromyotomy on the morphological state and the activities of some intracellular enzymes of the albino rat was studied histochemically. Within the first weeks after vagotomy, the pancreatic acini were found to diminish in size, and the beta-cells in the islets of Langerhans became oedematous. In the acini, the activities of succinate dehydrogenase, cytochrome oxidase, AS naphthol acetate esterase, and glucose-6-phosphatase were observed to decline, but the reactions for beta-glucuronidase and aryl sulphatase showed intensifications and polymorphic behaviour both in acinar and in islet cells. The latter also and particularly the beta-cells simultaneously revealed enhanced activities of succinate dehydrogenase, cytochrome oxidase, beta-glucuronidase, and aryl sulphatase, and an entire disappearance of the reaction for glucose-6-phosphatase. The alpha-cells increased their AS naphthol acetate esterase activity. After 5 weeks following vagotomy, morphological and enzymatic changes in the acini and islets were negligible, and after 5 and 9 months no differences were noted between the vagotomized rats and the control animals.", "contents": "Histochemical studies on the albino rat pancreas in different periods following vagotomy and simultaneous pyloromyotomy. The effect of complete subphrenic vagotomy and simultaneous pyloromyotomy on the morphological state and the activities of some intracellular enzymes of the albino rat was studied histochemically. Within the first weeks after vagotomy, the pancreatic acini were found to diminish in size, and the beta-cells in the islets of Langerhans became oedematous. In the acini, the activities of succinate dehydrogenase, cytochrome oxidase, AS naphthol acetate esterase, and glucose-6-phosphatase were observed to decline, but the reactions for beta-glucuronidase and aryl sulphatase showed intensifications and polymorphic behaviour both in acinar and in islet cells. The latter also and particularly the beta-cells simultaneously revealed enhanced activities of succinate dehydrogenase, cytochrome oxidase, beta-glucuronidase, and aryl sulphatase, and an entire disappearance of the reaction for glucose-6-phosphatase. The alpha-cells increased their AS naphthol acetate esterase activity. After 5 weeks following vagotomy, morphological and enzymatic changes in the acini and islets were negligible, and after 5 and 9 months no differences were noted between the vagotomized rats and the control animals."} {"id": "PMID:172416", "title": "[Physiological role of prostaglandins in adrenergic and non-adrenergic inhibitory neurotransmission in guinea pig taenia coli].", "content": "Prostaglandin (PG) E1, PGE2 and PGF2alpha and their biosynthesis inhibitor, indomethacin, were tested for their effects on the inhibitory responses of taenia induced by electrical stimulation of adrenergic and/or non-adrenergic inhibitory nerves in the perivascular nerve-taenia preparation isolated from guinea-pig caecum. The response to adrenergic nerve stimulation was considerably reduced by PGE1 and PGE2, while it was little affected by PGF2alpha. Although PGE1 and PGE2 produced contraction of taenia, it may be possible to dismiss from consideration their action of contraction of taenia in accounting for their inhibitory effect on the response to nerve stimulation since the following observations were made, 1) when the taenia were contracted by histamine, the response to adrenergic nerve stimulation was not reduced and 2) in the presence of polyphloretin phosphate, PGE1 and PGE2 did not contract taenia but reduced the response to adrenergic nerve stimulation. In the presence of indomethacin, the response to adrenergic nerve stimulation was increased greatly. On the contrary, the inhibitory response to non-adrenergic inhibitory nerve stimulation was not affected by application of PGE1, PGE2, PGF2alpha and indomethacin. These results suggest that endogenous PG of E series in guinea-pig taenia may play a role in modulating adrenergic neurotransmission. Attempts to demonstrate that PG could operate on a non-adrenergic inhibitory neurotransmission by a negative feedback mechanism were without success.", "contents": "[Physiological role of prostaglandins in adrenergic and non-adrenergic inhibitory neurotransmission in guinea pig taenia coli]. Prostaglandin (PG) E1, PGE2 and PGF2alpha and their biosynthesis inhibitor, indomethacin, were tested for their effects on the inhibitory responses of taenia induced by electrical stimulation of adrenergic and/or non-adrenergic inhibitory nerves in the perivascular nerve-taenia preparation isolated from guinea-pig caecum. The response to adrenergic nerve stimulation was considerably reduced by PGE1 and PGE2, while it was little affected by PGF2alpha. Although PGE1 and PGE2 produced contraction of taenia, it may be possible to dismiss from consideration their action of contraction of taenia in accounting for their inhibitory effect on the response to nerve stimulation since the following observations were made, 1) when the taenia were contracted by histamine, the response to adrenergic nerve stimulation was not reduced and 2) in the presence of polyphloretin phosphate, PGE1 and PGE2 did not contract taenia but reduced the response to adrenergic nerve stimulation. In the presence of indomethacin, the response to adrenergic nerve stimulation was increased greatly. On the contrary, the inhibitory response to non-adrenergic inhibitory nerve stimulation was not affected by application of PGE1, PGE2, PGF2alpha and indomethacin. These results suggest that endogenous PG of E series in guinea-pig taenia may play a role in modulating adrenergic neurotransmission. Attempts to demonstrate that PG could operate on a non-adrenergic inhibitory neurotransmission by a negative feedback mechanism were without success."} {"id": "PMID:172420", "title": "Correlation between various cell-surface antigens induced by murine leukemia virus in the rat: serological analysis.", "content": "Analysis based on the cytotoxicity test using antisera produced in rats indicated the presence of various cell-surface antigens on the tumors in WKA/Mk rats induced or artificially infected by Friend, Rauscher or Gross viruses. Each line of the tumor was found to have a common antigen, namely group-specific cell-surface antigen. A Gross type-specific and Friend and Rauscher type-specific cell-surface antigens were also detected, in keeping with the observations in the mouse system. In addition, the present experiments strongly suggested that a Friend strain-specific antigen was detected only on the cell-surface of the tumors in WAK/Mk rat induced or artificially infected by Friend virus. These results were in parallel with the data of previously reported transplantation studies.", "contents": "Correlation between various cell-surface antigens induced by murine leukemia virus in the rat: serological analysis. Analysis based on the cytotoxicity test using antisera produced in rats indicated the presence of various cell-surface antigens on the tumors in WKA/Mk rats induced or artificially infected by Friend, Rauscher or Gross viruses. Each line of the tumor was found to have a common antigen, namely group-specific cell-surface antigen. A Gross type-specific and Friend and Rauscher type-specific cell-surface antigens were also detected, in keeping with the observations in the mouse system. In addition, the present experiments strongly suggested that a Friend strain-specific antigen was detected only on the cell-surface of the tumors in WAK/Mk rat induced or artificially infected by Friend virus. These results were in parallel with the data of previously reported transplantation studies."} {"id": "PMID:172422", "title": "Isolation and partial characterization of an arginine-rich apolipoprotein from human plasma very-low-density lipoproteins: apolipoprotein E.", "content": "A water-insoluble apoprotein was isolated from apo-VLDL by column chromatography on Sephadex G-200 in sodium dodecylsulfate followed by preparative polyacrylamide gel electrophoresis in a discontinous sodium dodecylsulfate system, or by preparative electrophoresis alone. The protein was similar in amino acid composition to the \"arginine-rich protein\" reported by Shore and Shore. It represented about 10% of the total protein mass of VLDL. The apoprotein showed one single band with an apparent Mr of 39000 in sodium dodecylsulfate gel electrophoresis, and was homogeneous in gel electrophoresis at pH 8.9 In 8M urea. Immunochemical studies also showed homogeneity of this protein, and antisera prepared against it did not react with any other of the well known apolipoproteins, but did react with VLDL and apo-VLDL preparations. Analytical isoelectric focusing in 8M urea resulted in a heterogeneous banding pattern showing three major polypeptides with pI values of 5.5, 5.6 and 5.75. Thus this apolipoprotein clearly differs from the apo-B and apo-C polypeptides of VLDL as well as from apoproteins A and D in its molecular weight, amino acid composition, focusing behavior and immunochemical properties.", "contents": "Isolation and partial characterization of an arginine-rich apolipoprotein from human plasma very-low-density lipoproteins: apolipoprotein E. A water-insoluble apoprotein was isolated from apo-VLDL by column chromatography on Sephadex G-200 in sodium dodecylsulfate followed by preparative polyacrylamide gel electrophoresis in a discontinous sodium dodecylsulfate system, or by preparative electrophoresis alone. The protein was similar in amino acid composition to the \"arginine-rich protein\" reported by Shore and Shore. It represented about 10% of the total protein mass of VLDL. The apoprotein showed one single band with an apparent Mr of 39000 in sodium dodecylsulfate gel electrophoresis, and was homogeneous in gel electrophoresis at pH 8.9 In 8M urea. Immunochemical studies also showed homogeneity of this protein, and antisera prepared against it did not react with any other of the well known apolipoproteins, but did react with VLDL and apo-VLDL preparations. Analytical isoelectric focusing in 8M urea resulted in a heterogeneous banding pattern showing three major polypeptides with pI values of 5.5, 5.6 and 5.75. Thus this apolipoprotein clearly differs from the apo-B and apo-C polypeptides of VLDL as well as from apoproteins A and D in its molecular weight, amino acid composition, focusing behavior and immunochemical properties."} {"id": "PMID:172423", "title": "Studies on the asymmetric arrangement of membrane-lipid-enveloped virions as a model system.", "content": "Lipids of BHK 21 cells (baby hamster kidney) grown in tissue culture were labelled with radioactive fatty acids. The enveloped vesicular stomatitis virus was propagated in this host cell type. The virions were purified by density gradient centrifugation. Neuraminidase treatment of the intact virions led to a complete transformation of hematoside [N-acetylneuraminosyl(alpha2-3)lactosyl(beta1-1)ceramide] into lactosylceramide, with identical labelling of the ceramide portion in hematoside of the untreated virions and the lactosylceramide of the neuraminidase-treated particles. The morphology of the virions appeared unchanged in electron micrographs, but the neuraminic-acid-free virions had a strong tendency to aggregate. The results of these studies are evidence that gangliosides are integrated exclusively into the outer lamella of the lipid bilayer in the viral envelope. It is also evident that the viral envelope is a suitable model for studies on membrane asymmetry.", "contents": "Studies on the asymmetric arrangement of membrane-lipid-enveloped virions as a model system. Lipids of BHK 21 cells (baby hamster kidney) grown in tissue culture were labelled with radioactive fatty acids. The enveloped vesicular stomatitis virus was propagated in this host cell type. The virions were purified by density gradient centrifugation. Neuraminidase treatment of the intact virions led to a complete transformation of hematoside [N-acetylneuraminosyl(alpha2-3)lactosyl(beta1-1)ceramide] into lactosylceramide, with identical labelling of the ceramide portion in hematoside of the untreated virions and the lactosylceramide of the neuraminidase-treated particles. The morphology of the virions appeared unchanged in electron micrographs, but the neuraminic-acid-free virions had a strong tendency to aggregate. The results of these studies are evidence that gangliosides are integrated exclusively into the outer lamella of the lipid bilayer in the viral envelope. It is also evident that the viral envelope is a suitable model for studies on membrane asymmetry."} {"id": "PMID:172424", "title": "Identification of cytochrome a and a3 in yeast cells.", "content": "1) Cells of Saccharomyces cerevisiae have been analysed by single and double-bean spectroscopy. Evidence is given for two components of cytochrome c oxidase in the alpha-region of their absorption spectrum. A rapidly reduceable component with a maximum at 600 nm and a slowly reduceable component with a maximum at 604 nm contribute about equal amounts to the total alpha-absorption of cytochrome c oxidase. 2) The component absorbing at 600 nm was identified as the high-potential component with a redox potential of 340 - 355mV, and the 604-nm component as the low-potential component of cytochrome c oxidase with redox potential of 180 - 190 mV. 3) Both components can be characterized by analysing the reduction kinetics in the presence of carbon monoxide. In the presence of saturating concentrations of carbon monoxide, an oxygen pulse leads to a rapid oxidation and subsequent reduction of cytochrome c oxidase, but the rapid reduction phase at 600 nm completely disappears, demonstrating its identity with cytochrome a3, which, being liganded by carbon monoxide in its reduced state, cannot react any more. The component which becomes oxidized and later reduced in the presence of carbon monoxide -- by definition cytochrome a -- has an absorption maximum at 604 nm. 4) The total extinction change at 604 nm in the presence of carbon monoxide is nearly as high as in its absence, but the reduction occurs in two phases and only the second phase, which contributes 50 - 60% to the total absorbance, corresponds in redox potential and kinetic properties to cytochrome a. Because the redox potential of the first reduction phase is very close to that of the low-potential copper atom of cytochrome c oxidase, it is concluded that the apparent increase in the extinction coefficient of cytochrome a in the presence of carbon monoxide is the result of a strong interaction between the ligand fields of cytochrome a and copper, induced by the binding of carbon monoxide to reduced cytochrome a3.", "contents": "Identification of cytochrome a and a3 in yeast cells. 1) Cells of Saccharomyces cerevisiae have been analysed by single and double-bean spectroscopy. Evidence is given for two components of cytochrome c oxidase in the alpha-region of their absorption spectrum. A rapidly reduceable component with a maximum at 600 nm and a slowly reduceable component with a maximum at 604 nm contribute about equal amounts to the total alpha-absorption of cytochrome c oxidase. 2) The component absorbing at 600 nm was identified as the high-potential component with a redox potential of 340 - 355mV, and the 604-nm component as the low-potential component of cytochrome c oxidase with redox potential of 180 - 190 mV. 3) Both components can be characterized by analysing the reduction kinetics in the presence of carbon monoxide. In the presence of saturating concentrations of carbon monoxide, an oxygen pulse leads to a rapid oxidation and subsequent reduction of cytochrome c oxidase, but the rapid reduction phase at 600 nm completely disappears, demonstrating its identity with cytochrome a3, which, being liganded by carbon monoxide in its reduced state, cannot react any more. The component which becomes oxidized and later reduced in the presence of carbon monoxide -- by definition cytochrome a -- has an absorption maximum at 604 nm. 4) The total extinction change at 604 nm in the presence of carbon monoxide is nearly as high as in its absence, but the reduction occurs in two phases and only the second phase, which contributes 50 - 60% to the total absorbance, corresponds in redox potential and kinetic properties to cytochrome a. Because the redox potential of the first reduction phase is very close to that of the low-potential copper atom of cytochrome c oxidase, it is concluded that the apparent increase in the extinction coefficient of cytochrome a in the presence of carbon monoxide is the result of a strong interaction between the ligand fields of cytochrome a and copper, induced by the binding of carbon monoxide to reduced cytochrome a3."} {"id": "PMID:172426", "title": "Short-term follow-up after brief inpatient treatment.", "content": "A total of 110 patients admitted to the inpatient unit of a community mental health center in Philadelphia were followed up between 90 and 120 days after discharge to determine their level of functioning after an average hospital stay of 21 days. All but five of the patients were referred for aftercare, and 80 received outpatient or day hospital care after their release. Sixteen patients were readmitted to inpatient care within 90 days after discharge. The author describes the patients' social and community adjustment at follow-up, based on information obtained from aftercare therapists.", "contents": "Short-term follow-up after brief inpatient treatment. A total of 110 patients admitted to the inpatient unit of a community mental health center in Philadelphia were followed up between 90 and 120 days after discharge to determine their level of functioning after an average hospital stay of 21 days. All but five of the patients were referred for aftercare, and 80 received outpatient or day hospital care after their release. Sixteen patients were readmitted to inpatient care within 90 days after discharge. The author describes the patients' social and community adjustment at follow-up, based on information obtained from aftercare therapists."} {"id": "PMID:172427", "title": "Short-term versus long-term hospitalization in a private psychiatric facility: a follow-up study.", "content": "A follow-up study was made of 43 short-term and 42 long-term ex-patients 18 months after their discharge from a private psychiatric hospital. The short-term sample was different from the long-term sample on many preadmission and hospitalization variables, but it was much less different on the follow-up variables. Although most ex-patients in both samples were functioning well at follow-up, the long-term sample was doing somewhat better in all areas, according to both the former patients and their nearest relatives. Differences between the improvement of those in the short- and long-term sample increased when tested by diagnosis; long-term schizophrenic patients improved the most.", "contents": "Short-term versus long-term hospitalization in a private psychiatric facility: a follow-up study. A follow-up study was made of 43 short-term and 42 long-term ex-patients 18 months after their discharge from a private psychiatric hospital. The short-term sample was different from the long-term sample on many preadmission and hospitalization variables, but it was much less different on the follow-up variables. Although most ex-patients in both samples were functioning well at follow-up, the long-term sample was doing somewhat better in all areas, according to both the former patients and their nearest relatives. Differences between the improvement of those in the short- and long-term sample increased when tested by diagnosis; long-term schizophrenic patients improved the most."} {"id": "PMID:172428", "title": "A follow-up study of clients discharged from a day hospital aftercare program.", "content": "Sixty-one former clients of a day hospital aftercare program were assessed for level of social and individual functioning. They were found to be more like psychiatric patients than like the normal population. Marital status and type of residential arrangement were the only demographic variables that could be correlated with level of functioning. Married clients functioned better than those who were not married, and boarding-home residents were significantly more impaired than those in other living situations. Although the data did not permit conclusions about the effectiveness of the aftercare program, they suggested the need for improved conditions in boarding homes.", "contents": "A follow-up study of clients discharged from a day hospital aftercare program. Sixty-one former clients of a day hospital aftercare program were assessed for level of social and individual functioning. They were found to be more like psychiatric patients than like the normal population. Marital status and type of residential arrangement were the only demographic variables that could be correlated with level of functioning. Married clients functioned better than those who were not married, and boarding-home residents were significantly more impaired than those in other living situations. Although the data did not permit conclusions about the effectiveness of the aftercare program, they suggested the need for improved conditions in boarding homes."} {"id": "PMID:172430", "title": "Giant cell carcinoma of the lung. A light and electron microscopic study.", "content": "Three cases of giant cell carcinoma of lung and six other lung carcinomas with large atypical cell formation were studied by both light and electron microscopy. The giant cell carcinomas showed unique light and electron microscopic features, whereas large atypical cells from other lung carcinomas usually retained some ultrastructural characteristics of their cellular origin. The giant cell carcinoma is characterized by abundant mitochondria, a concentric whorl of tonofilament-like fibrils, and aggregates of several pairs of centrioles. The \"phagocytic activity\" of the giant cell carcinoma is more likely attributable to the so-called tumor cell-tumor cell or leukocyte-tumor cell emperipolesis. Giant cell carcinoma of lung may originate from a primitive multipotential cell in the distal bronchiole or be associated with a squamous, glandular, or clear cell pattern. Whether in pure or mixed form, this tumor should still be considered a specific entity because of its unique light and electron microscopic features and the fulminant clinical course it follows despite rate reported exceptions.", "contents": "Giant cell carcinoma of the lung. A light and electron microscopic study. Three cases of giant cell carcinoma of lung and six other lung carcinomas with large atypical cell formation were studied by both light and electron microscopy. The giant cell carcinomas showed unique light and electron microscopic features, whereas large atypical cells from other lung carcinomas usually retained some ultrastructural characteristics of their cellular origin. The giant cell carcinoma is characterized by abundant mitochondria, a concentric whorl of tonofilament-like fibrils, and aggregates of several pairs of centrioles. The \"phagocytic activity\" of the giant cell carcinoma is more likely attributable to the so-called tumor cell-tumor cell or leukocyte-tumor cell emperipolesis. Giant cell carcinoma of lung may originate from a primitive multipotential cell in the distal bronchiole or be associated with a squamous, glandular, or clear cell pattern. Whether in pure or mixed form, this tumor should still be considered a specific entity because of its unique light and electron microscopic features and the fulminant clinical course it follows despite rate reported exceptions."} {"id": "PMID:172433", "title": "Insect cell culture: improved media and methods for initiating attached cell lines from the Lepidoptera.", "content": "Several cell lines from the pupae of the noctuid moth species Spodoptera frugiperda, Heliothis zea, and Trichoplusia ni were isolated on a synthetic medium containing insect hemolymph and turkey serum. These lines were progressively adapted to improved media free of insect hemolymph but containing one or more of the following sera: turkey, chicken, and fetal calf. Primary culture tissue disruption was improved by substituting collagenase for trypsin. Primary culture survival was improved by controlling the total tissue volume per unit medium volum, and by the addition of glutathione to prevent melanization and to improve cell adherence to the substrate. Culture servival was also improved by heat treatment of sera, control of medium osmolality, and changes in the basal medium and serum supplementation. Some of these changes also resulted in improved growth giving higher maximal cell counts. Comparative cell growth on the various media was graphed and generation times given.", "contents": "Insect cell culture: improved media and methods for initiating attached cell lines from the Lepidoptera. Several cell lines from the pupae of the noctuid moth species Spodoptera frugiperda, Heliothis zea, and Trichoplusia ni were isolated on a synthetic medium containing insect hemolymph and turkey serum. These lines were progressively adapted to improved media free of insect hemolymph but containing one or more of the following sera: turkey, chicken, and fetal calf. Primary culture tissue disruption was improved by substituting collagenase for trypsin. Primary culture survival was improved by controlling the total tissue volume per unit medium volum, and by the addition of glutathione to prevent melanization and to improve cell adherence to the substrate. Culture servival was also improved by heat treatment of sera, control of medium osmolality, and changes in the basal medium and serum supplementation. Some of these changes also resulted in improved growth giving higher maximal cell counts. Comparative cell growth on the various media was graphed and generation times given."} {"id": "PMID:172437", "title": "Influence of culture conditions of growth of FL-74 cells and feline oncornavirus cell membrane associated antigen production.", "content": "The FL-74 cell, a feline lymphoblastoid cell line derived from a tumor induced by leukemia virus, grows equally well in static suspension culture (plastic T-flask or silicone treated glass bottles) or in spinner culture. No growth was observed in unsiliconized glass bottles. Although feline leukemia virus production was nearly the same in FL-74 grown in each of the above types of vessel, the expression of the feline oncornavirus membrane associated antigen (FOCMA), as determined by membrane immunofluorescence, was more intense and more complete on cells grown in static suspension. Moreover, higher fluorescent antibody titer endpoints were observed with cells from static suspension cultures than with cells from spinner cultures, FL-74 cells grown in spinner culture, when subjected to partial synchrony by cold block or by deprivation of essential amino acids (arginine and/or isoleucine) for 12 hr, achieved a membrane fluorescent pattern for FOCMA similar to cells grown in static suspension. It is proposed that the expression of FOCMA on the cell membrane surface is cell-cycle dependent, and that the rate at which a cell passes through the cell cycle determines the pattern and intensity of the fluorescence of the cell membrane.", "contents": "Influence of culture conditions of growth of FL-74 cells and feline oncornavirus cell membrane associated antigen production. The FL-74 cell, a feline lymphoblastoid cell line derived from a tumor induced by leukemia virus, grows equally well in static suspension culture (plastic T-flask or silicone treated glass bottles) or in spinner culture. No growth was observed in unsiliconized glass bottles. Although feline leukemia virus production was nearly the same in FL-74 grown in each of the above types of vessel, the expression of the feline oncornavirus membrane associated antigen (FOCMA), as determined by membrane immunofluorescence, was more intense and more complete on cells grown in static suspension. Moreover, higher fluorescent antibody titer endpoints were observed with cells from static suspension cultures than with cells from spinner cultures, FL-74 cells grown in spinner culture, when subjected to partial synchrony by cold block or by deprivation of essential amino acids (arginine and/or isoleucine) for 12 hr, achieved a membrane fluorescent pattern for FOCMA similar to cells grown in static suspension. It is proposed that the expression of FOCMA on the cell membrane surface is cell-cycle dependent, and that the rate at which a cell passes through the cell cycle determines the pattern and intensity of the fluorescence of the cell membrane."} {"id": "PMID:172436", "title": "The positive control of cell proliferation by the interplay on calcium ions and cyclic nucleotides. A review.", "content": "Calcium, cyclic AMP, and cyclic GMP do not seem to be involved in proliferative activation of postmitotic differentiated cells. Instead, they are intracycle regulators, and we propose the following working model of their control of the initiation of DNA synthesis. While a role for cyclic GMP cannot yet be defined, a brief postmitotic burst of its synthesis might serve to prevent certain activated cells (e.g. 3T3 mouse cells) from being diverted into a nonproliferating (but still activated) G0 state (Figs. 1 and 17). In a latter part of the G1 phase, something happens to stimulate briefly the synthesis of cyclic AMP which, in turn, drives calcium ions from the mitochondria into the cytosol to activate newly synthesized thymidylate synthetase (or other primed enzymic assemblies) (Fig. 1). Having \"turned on\" their target enzymes, the accumulated cyclic AMP is destroyed and the excess calcium ions are reaccumulated by the mitochondria to avoid interfering with succeeding reactions. This model predicts that persistent changes in cyclic AMP metabolism and the respiration-linked, calcium-accumulating (ion-buffering) activity of mitochondria may be responsible for the sustained growth of tumors.", "contents": "The positive control of cell proliferation by the interplay on calcium ions and cyclic nucleotides. A review. Calcium, cyclic AMP, and cyclic GMP do not seem to be involved in proliferative activation of postmitotic differentiated cells. Instead, they are intracycle regulators, and we propose the following working model of their control of the initiation of DNA synthesis. While a role for cyclic GMP cannot yet be defined, a brief postmitotic burst of its synthesis might serve to prevent certain activated cells (e.g. 3T3 mouse cells) from being diverted into a nonproliferating (but still activated) G0 state (Figs. 1 and 17). In a latter part of the G1 phase, something happens to stimulate briefly the synthesis of cyclic AMP which, in turn, drives calcium ions from the mitochondria into the cytosol to activate newly synthesized thymidylate synthetase (or other primed enzymic assemblies) (Fig. 1). Having \"turned on\" their target enzymes, the accumulated cyclic AMP is destroyed and the excess calcium ions are reaccumulated by the mitochondria to avoid interfering with succeeding reactions. This model predicts that persistent changes in cyclic AMP metabolism and the respiration-linked, calcium-accumulating (ion-buffering) activity of mitochondria may be responsible for the sustained growth of tumors."} {"id": "PMID:172438", "title": "Organ culture of human nervous system tumors.", "content": "Tumors of the human nervous system (neuroblastomas, an ependymoma, a medulloblastoma, and a Schwannoma) obtained during surgery have been cultured organotypically by the method of Wolff. The tumors retained characteristic morphology, organization and patterns of behavior in vitro, and one neuroblastoma gave rise to a growing long-term culture. Long-term organotypic culture, where maintenance of tissue organization and growth occur together, is recommended for the study of neoplasms of the nervous system.", "contents": "Organ culture of human nervous system tumors. Tumors of the human nervous system (neuroblastomas, an ependymoma, a medulloblastoma, and a Schwannoma) obtained during surgery have been cultured organotypically by the method of Wolff. The tumors retained characteristic morphology, organization and patterns of behavior in vitro, and one neuroblastoma gave rise to a growing long-term culture. Long-term organotypic culture, where maintenance of tissue organization and growth occur together, is recommended for the study of neoplasms of the nervous system."} {"id": "PMID:172439", "title": "Fine structure of a murine mammary carcinoma cell line.", "content": "A fine structural study was made of cells from the epithelioid MCF-8/5-2A cell line derived from a MuMTV-free D2 transplantable hyperplastic outgrowth. Electron microscopy shows the cells to be truly epithelial with many cell-to-cell junctions and microvilli. The cells are similar in many respects to normal mouse mammary gland and some of the conventional mammary tumor derived cell lines. This study supports previous observations of the absence of MuMTV in MCF-8 within the limits of morphological detection, and demonstrates the presence of numerous virus particles within, or budding into, cisternae of the endoplasmic reticulum and nuclear envelope. These intracisternal A particles have not been previously described in such abundance in mammary tumor tissue culture cells.", "contents": "Fine structure of a murine mammary carcinoma cell line. A fine structural study was made of cells from the epithelioid MCF-8/5-2A cell line derived from a MuMTV-free D2 transplantable hyperplastic outgrowth. Electron microscopy shows the cells to be truly epithelial with many cell-to-cell junctions and microvilli. The cells are similar in many respects to normal mouse mammary gland and some of the conventional mammary tumor derived cell lines. This study supports previous observations of the absence of MuMTV in MCF-8 within the limits of morphological detection, and demonstrates the presence of numerous virus particles within, or budding into, cisternae of the endoplasmic reticulum and nuclear envelope. These intracisternal A particles have not been previously described in such abundance in mammary tumor tissue culture cells."} {"id": "PMID:172435", "title": "Elevation of adenosine 3',5'-cyclic monophosphate in established mamalian cell strains by Hypaque (sodium diatrizoate).", "content": "Hypaque (sodium diatrizoate), when added to cells growing in culture (two HeLa S3 strains, rat glioblastoma C6 and mouse lymphoma L5178Y), increased the intracellular level of adenosine 3',5'-cyclic monophosphate. A transient elevation of adenosine 3',5'-cyclic monophosphate was also observed when L5178Y cells were subjected to a procedure recommended for separation of lymphocytes from peripheral blood. The effect of Hypaque did not appear to be related to the increase in osmolality of the medium.", "contents": "Elevation of adenosine 3',5'-cyclic monophosphate in established mamalian cell strains by Hypaque (sodium diatrizoate). Hypaque (sodium diatrizoate), when added to cells growing in culture (two HeLa S3 strains, rat glioblastoma C6 and mouse lymphoma L5178Y), increased the intracellular level of adenosine 3',5'-cyclic monophosphate. A transient elevation of adenosine 3',5'-cyclic monophosphate was also observed when L5178Y cells were subjected to a procedure recommended for separation of lymphocytes from peripheral blood. The effect of Hypaque did not appear to be related to the increase in osmolality of the medium."} {"id": "PMID:172440", "title": "Fine structural and cytochemical studies of human diploid fibroblasts arrested in an essentially nonmitotic state.", "content": "Human diploid fibroblasts can be maintained in vitro in an arrested, essentially nonmitotic state for extended periods of time by reducing the serum concentration in the medium from 10 to 0.5%. Arrested cells can be induced to re-enter the proliferative state by subcultivation in medium containing 10% serum. Fine structure, acid phosphatase, cytochrome oxidase, and extracellular carbohydrates in arrested cells were examined and compared to cultures growing in 10% serum and to cells transferred to 10% serum after 21 days in 0.5% serum. Cells in 10% serum posessed a well-developed Golgi complex, extensive rough endoplasmic reticulum, mitochondria containing transverse cristae, and many free ribosomes in the cytoplasm. In arrested cells, Golgi complexes were rarely observed, the number of both free and membrane-bound ribosomes was reduced, the number of cristae per mitochondria was decreased and the amount of demonstrable cytochrome oxidase activity was diminished. There was an accumulation of intercellular carbohydrate components. After subcultivation with medium containing 10% serum, arrested cells regained the ultrastructural characteristics of cells continuously cultured at this serum level; however, the amount of intercellular carbohydrate remained elevated. These results indicate that distinct yet reversible changes occur in the subcellular morphology and organization of cells maintained in an essentially nonmitotic state. This arrested state may be a close approximation to the situation as it occurs in vivo in expanding cell populations.", "contents": "Fine structural and cytochemical studies of human diploid fibroblasts arrested in an essentially nonmitotic state. Human diploid fibroblasts can be maintained in vitro in an arrested, essentially nonmitotic state for extended periods of time by reducing the serum concentration in the medium from 10 to 0.5%. Arrested cells can be induced to re-enter the proliferative state by subcultivation in medium containing 10% serum. Fine structure, acid phosphatase, cytochrome oxidase, and extracellular carbohydrates in arrested cells were examined and compared to cultures growing in 10% serum and to cells transferred to 10% serum after 21 days in 0.5% serum. Cells in 10% serum posessed a well-developed Golgi complex, extensive rough endoplasmic reticulum, mitochondria containing transverse cristae, and many free ribosomes in the cytoplasm. In arrested cells, Golgi complexes were rarely observed, the number of both free and membrane-bound ribosomes was reduced, the number of cristae per mitochondria was decreased and the amount of demonstrable cytochrome oxidase activity was diminished. There was an accumulation of intercellular carbohydrate components. After subcultivation with medium containing 10% serum, arrested cells regained the ultrastructural characteristics of cells continuously cultured at this serum level; however, the amount of intercellular carbohydrate remained elevated. These results indicate that distinct yet reversible changes occur in the subcellular morphology and organization of cells maintained in an essentially nonmitotic state. This arrested state may be a close approximation to the situation as it occurs in vivo in expanding cell populations."} {"id": "PMID:172434", "title": "Detection of bovine viruses in fetal bovine serum used in cell culture.", "content": "This investigation employed a viral screening method detect endogenous bovine virus contaminants in commercially supplied fetal bovine serum. Fifty-one lots of fetal bovine serum from 14 suppliers were examined. Over 30% of the lots tested were found to contain bovine viruses; they included bovine virus diarrhea virus, parainfluenza type3-like virus, bovine herpesvirus-1, bovine enterovirus type 4, and an unidentified cytopathogenic agent. Of the 51 lots, 20 had been pretested by the suppliers and were considered to be free of known viral contaminants. Our viral screening methods revealed that five of these pretested lots, or 25%, contained endogenous bovine viruses.", "contents": "Detection of bovine viruses in fetal bovine serum used in cell culture. This investigation employed a viral screening method detect endogenous bovine virus contaminants in commercially supplied fetal bovine serum. Fifty-one lots of fetal bovine serum from 14 suppliers were examined. Over 30% of the lots tested were found to contain bovine viruses; they included bovine virus diarrhea virus, parainfluenza type3-like virus, bovine herpesvirus-1, bovine enterovirus type 4, and an unidentified cytopathogenic agent. Of the 51 lots, 20 had been pretested by the suppliers and were considered to be free of known viral contaminants. Our viral screening methods revealed that five of these pretested lots, or 25%, contained endogenous bovine viruses."} {"id": "PMID:172445", "title": "Interaction of cholera enterotoxin with cultured adrenal tumor cells.", "content": "In the adrenal tumor cell system ganglioside Gm1 inhibited cholera enterotoxin (CT)-induced steroidogenesis if it was preincubated with the toxin or added to adrenal cells 10 min before CT. In the preincubation studies a molar ratio of Gm1 to toxin of 3:1 was necessary for half-maximal inhibition of steroidogenesis. On the other hand, horse serum anticholeragenoid neutralized the steroidogenic response to cell-bound CT by 50% if it was added to adrenal monolayer cultures 15 min after the toxin. Specific antiserum was able to neutralized 20% of the toxin-induced activity even if it was added to adrenal cultures 2 h after CT. Phase contrast microscopy demonstrated that partial neutralization of the biochemical effect of CT by horse serum anticholeragenoid was accompanied by partial prevention of toxin-induced rounding of adrenal cells. Further studies showed that pretreatment of cultured adrenal cells with a maximal dose of CT increased cyclic adenosine 3'-5'-monophosphate formation in response to a maximal stimulating dose of adrenocorticotropin. This result suggested potentiation of hormonal activation of adenylate cyclase in intact adrenal tumor cells in response to CT.", "contents": "Interaction of cholera enterotoxin with cultured adrenal tumor cells. In the adrenal tumor cell system ganglioside Gm1 inhibited cholera enterotoxin (CT)-induced steroidogenesis if it was preincubated with the toxin or added to adrenal cells 10 min before CT. In the preincubation studies a molar ratio of Gm1 to toxin of 3:1 was necessary for half-maximal inhibition of steroidogenesis. On the other hand, horse serum anticholeragenoid neutralized the steroidogenic response to cell-bound CT by 50% if it was added to adrenal monolayer cultures 15 min after the toxin. Specific antiserum was able to neutralized 20% of the toxin-induced activity even if it was added to adrenal cultures 2 h after CT. Phase contrast microscopy demonstrated that partial neutralization of the biochemical effect of CT by horse serum anticholeragenoid was accompanied by partial prevention of toxin-induced rounding of adrenal cells. Further studies showed that pretreatment of cultured adrenal cells with a maximal dose of CT increased cyclic adenosine 3'-5'-monophosphate formation in response to a maximal stimulating dose of adrenocorticotropin. This result suggested potentiation of hormonal activation of adenylate cyclase in intact adrenal tumor cells in response to CT."} {"id": "PMID:172446", "title": "Fate of human lactoferrin and myeloperoxidase in phagocytizing human neutrophils: effects of immunoglobulin G subclasses and immune complexes coated on latex beads.", "content": "Human neutrophils (PMN) degranulated in response to soluble human immune complexes and to myeloma proteins, including subclasses of immunoglobulin G (IgG)1, IgG2, IgG3, and IgG4 coated on 1.09-mum latex beads. Immunochemical measurement of lactoferrin (LF) from specific granules and myeloperoxidas (MPO) from azurophil granules showed that both classes of granule degranulated. Beads with soluble complexes of human anti-pigeon IgG-normal pigeon IgG, prepared from serum of a patient with pigeon breeders disease, induced significantly greater degranulation than did pigeon IgG-coated beads. Up to 40% of LF in the PMN degranulated during phagocytic challenge and 86% of that entered the extracellular fluid. Twenty to 30% of the MPO degranulated, but less than 50% of that entered the extracellular fluid. The degranulated LF and MPO which remained in the PMN were recovered from phagocytic vacuoles. Beads coated with purified human myeloma proteins (12 different ones, three of each subclass) induced degranulation in the order IgG3 greater than IgG1 greater than IgG2 greater than IgG4; however, these differences were found to be a function of the amount of latex ingested. Thus, the amount of degranulation was dependent more on the opsonizing capacity of the immunoglobulins rather than on their intrinsic capacities for inducing degranulation. Degranulation of both LF and MPO in response to IgG subclasses followed patterns similar to those caused by soluble immune complexes, and IgG3 coated on beads caused degranulation equal to that caused by human complex-coated beads. Degranulation to IgG3 and IgG4 was uninfluenced by fresh compared with heat-inactivated human AB serum. This was true although IgG3 beads fixed greater than sixfold more complement than did IgG4 beads. Evidently human IgG subclasses enhance phagocytosis and degranulation of human PMN. The overwhelmingly extracellular degranulation of LF in response to various bead coating suggest that it subserves a major protion of it role outside PMN.", "contents": "Fate of human lactoferrin and myeloperoxidase in phagocytizing human neutrophils: effects of immunoglobulin G subclasses and immune complexes coated on latex beads. Human neutrophils (PMN) degranulated in response to soluble human immune complexes and to myeloma proteins, including subclasses of immunoglobulin G (IgG)1, IgG2, IgG3, and IgG4 coated on 1.09-mum latex beads. Immunochemical measurement of lactoferrin (LF) from specific granules and myeloperoxidas (MPO) from azurophil granules showed that both classes of granule degranulated. Beads with soluble complexes of human anti-pigeon IgG-normal pigeon IgG, prepared from serum of a patient with pigeon breeders disease, induced significantly greater degranulation than did pigeon IgG-coated beads. Up to 40% of LF in the PMN degranulated during phagocytic challenge and 86% of that entered the extracellular fluid. Twenty to 30% of the MPO degranulated, but less than 50% of that entered the extracellular fluid. The degranulated LF and MPO which remained in the PMN were recovered from phagocytic vacuoles. Beads coated with purified human myeloma proteins (12 different ones, three of each subclass) induced degranulation in the order IgG3 greater than IgG1 greater than IgG2 greater than IgG4; however, these differences were found to be a function of the amount of latex ingested. Thus, the amount of degranulation was dependent more on the opsonizing capacity of the immunoglobulins rather than on their intrinsic capacities for inducing degranulation. Degranulation of both LF and MPO in response to IgG subclasses followed patterns similar to those caused by soluble immune complexes, and IgG3 coated on beads caused degranulation equal to that caused by human complex-coated beads. Degranulation to IgG3 and IgG4 was uninfluenced by fresh compared with heat-inactivated human AB serum. This was true although IgG3 beads fixed greater than sixfold more complement than did IgG4 beads. Evidently human IgG subclasses enhance phagocytosis and degranulation of human PMN. The overwhelmingly extracellular degranulation of LF in response to various bead coating suggest that it subserves a major protion of it role outside PMN."} {"id": "PMID:172447", "title": "Effect of staphylococcal protein A on complement-potentiated neutralization of herpes simplex virus and immune lysis of virus-infected cells.", "content": "Interaction of staphylococcal protein A (SPA) with human serum depressed the ability of such serum to neutralize herpes simpled virus (HSV)-antibody labialis. SPA-induced depression of serum-dependent virus neutralization appeared to be due to consumption of complement by SPA. In addition, SPA attached to antibody-treated, HSV-infected cells and inhibited complement mediated immune cytolysis. The amount of inhibition obtained depended upon the with the infected cells. The possible significance of SPA in the pathogenesis of viral disease complicated by secondary staphylococcal infection is discussed.", "contents": "Effect of staphylococcal protein A on complement-potentiated neutralization of herpes simplex virus and immune lysis of virus-infected cells. Interaction of staphylococcal protein A (SPA) with human serum depressed the ability of such serum to neutralize herpes simpled virus (HSV)-antibody labialis. SPA-induced depression of serum-dependent virus neutralization appeared to be due to consumption of complement by SPA. In addition, SPA attached to antibody-treated, HSV-infected cells and inhibited complement mediated immune cytolysis. The amount of inhibition obtained depended upon the with the infected cells. The possible significance of SPA in the pathogenesis of viral disease complicated by secondary staphylococcal infection is discussed."} {"id": "PMID:172448", "title": "Murine cytomegalovirus: induction of and sensitivity to interferon in vitro.", "content": "Moderate amounts of viral inhibitor were produced by mouse embryo (ME) cultures infected with two strains of plaque-purified murine cytomegalovirus (MCV). This inhibitor was shown to be interferon, based on the possession of similar properties. The growth studies of MCV in ME cells showed that interferon was produced as early as 4 h after infection, infectious virus was produced between 12 to 16 h, and cytopathic effect was produced between 16 to 18 h. Since MCV-induced interferon production and the subsequent development of antiviral state occurred early, the long eclipse period may be due to an interferon-mediated delay of virus replication. Pretreatment of ME cells with varying concentrations of interferon before infection with MCV did not result in increased interferon production, but at high pretreatment doses a slight inhibitory effect on interferon production was observed. In vitro sensitivity studies showed that small doses of MCV were highly sensitive to the antiviral action of interferon, but higher viral doses proved to be markedly resistant. Although the available evidence does not permit a definitive interpretation of the mechanism by which MCV may show differing sensitivities to interferon action, the presence of a small interferon-resistant fraction of virus-infected cells may account for the observations.", "contents": "Murine cytomegalovirus: induction of and sensitivity to interferon in vitro. Moderate amounts of viral inhibitor were produced by mouse embryo (ME) cultures infected with two strains of plaque-purified murine cytomegalovirus (MCV). This inhibitor was shown to be interferon, based on the possession of similar properties. The growth studies of MCV in ME cells showed that interferon was produced as early as 4 h after infection, infectious virus was produced between 12 to 16 h, and cytopathic effect was produced between 16 to 18 h. Since MCV-induced interferon production and the subsequent development of antiviral state occurred early, the long eclipse period may be due to an interferon-mediated delay of virus replication. Pretreatment of ME cells with varying concentrations of interferon before infection with MCV did not result in increased interferon production, but at high pretreatment doses a slight inhibitory effect on interferon production was observed. In vitro sensitivity studies showed that small doses of MCV were highly sensitive to the antiviral action of interferon, but higher viral doses proved to be markedly resistant. Although the available evidence does not permit a definitive interpretation of the mechanism by which MCV may show differing sensitivities to interferon action, the presence of a small interferon-resistant fraction of virus-infected cells may account for the observations."} {"id": "PMID:172449", "title": "Inhibition of the mitogenic response of normal peripheral lymphocytes by extracts or supernatant fluids of a Herpesvirus saimiri lymphoid tumor cell line.", "content": "A Herpesvirus saimiri-infected marmoset lymphoid cell line (MLC-1) was examined for the presence of soluble factors which might affect lymphocyte functions and, therefore, relate to the pathogenesis of lymphoma in vivo. MLC-1 cells, cell extracts, and culture fluids were shown to reduce the spontaneous deoxyribonucleic acid (DNA) synthesis of normal peripheral blood lymphocytes and to completely inhibit their response to phytohemagglutinin (PHA). Suppression of PHA response was demonstrated against a variety of human and nonhuman primate species, with 90 to 95% inhibition occurring at dilutions of extract as great as 1:5,120. Inhibition of this type was also demonstrated using extracts of two of five other lymphoblastoid cell lines tested. Physical-chemical characteristics of the active factor(s) revealed a non-sedimentable, non-dialyzable, trypsin-resistant molecule, which was stable at 56 C for 30 min but inactivated at 80 C for 30 min. The factor(s) also exerted an effect on some but not all established lymphoblastoid cell lines, where DNA, ribonucleic acid, and protein synthesis were all inhibited, with DNA synthesis being the most affected (95% suppression). Cellular respiration was not affected by the presence of the factor(s), and the inhibition of DNA synthesis was reversible after 24 h. Purified human interferon did not reduce the PHA response of normal owl monkey peripheral blood lymphocytes and was less effective against an established lymphoblastoid cell line than the MLC-1 extract. Antiviral activity was also demonstrated in the preparations and may represent interferon, which these cells are known to produce at low levels.", "contents": "Inhibition of the mitogenic response of normal peripheral lymphocytes by extracts or supernatant fluids of a Herpesvirus saimiri lymphoid tumor cell line. A Herpesvirus saimiri-infected marmoset lymphoid cell line (MLC-1) was examined for the presence of soluble factors which might affect lymphocyte functions and, therefore, relate to the pathogenesis of lymphoma in vivo. MLC-1 cells, cell extracts, and culture fluids were shown to reduce the spontaneous deoxyribonucleic acid (DNA) synthesis of normal peripheral blood lymphocytes and to completely inhibit their response to phytohemagglutinin (PHA). Suppression of PHA response was demonstrated against a variety of human and nonhuman primate species, with 90 to 95% inhibition occurring at dilutions of extract as great as 1:5,120. Inhibition of this type was also demonstrated using extracts of two of five other lymphoblastoid cell lines tested. Physical-chemical characteristics of the active factor(s) revealed a non-sedimentable, non-dialyzable, trypsin-resistant molecule, which was stable at 56 C for 30 min but inactivated at 80 C for 30 min. The factor(s) also exerted an effect on some but not all established lymphoblastoid cell lines, where DNA, ribonucleic acid, and protein synthesis were all inhibited, with DNA synthesis being the most affected (95% suppression). Cellular respiration was not affected by the presence of the factor(s), and the inhibition of DNA synthesis was reversible after 24 h. Purified human interferon did not reduce the PHA response of normal owl monkey peripheral blood lymphocytes and was less effective against an established lymphoblastoid cell line than the MLC-1 extract. Antiviral activity was also demonstrated in the preparations and may represent interferon, which these cells are known to produce at low levels."} {"id": "PMID:172450", "title": "Effect of pretreatment with Mycobacterium bovis (strain BCG) and immune syphilitic serum on rabbit resistance to Treponema pallidum.", "content": "Stimulation of the rabbit reticuloendothelial system with viable Mycobacterium bovis (strain BCG), and other agents, had no effect on the development of syphilitic lesions after intradermal or intravenous inoculation with graded doses of Treponema pallidum (virulent Nichol's strain; mean infective doses less than 10). The simultaneous administration of immune syphilitic rabbit serum retarded the development of lesions, but this appeared to be due solely to the immune serum, suggesting no synergism between the activated reticuloendothelial system and the anti-T. pallidum antibodies. The administration of two doses of BCG enhanced syphilitic lesion development in the rabbit.", "contents": "Effect of pretreatment with Mycobacterium bovis (strain BCG) and immune syphilitic serum on rabbit resistance to Treponema pallidum. Stimulation of the rabbit reticuloendothelial system with viable Mycobacterium bovis (strain BCG), and other agents, had no effect on the development of syphilitic lesions after intradermal or intravenous inoculation with graded doses of Treponema pallidum (virulent Nichol's strain; mean infective doses less than 10). The simultaneous administration of immune syphilitic rabbit serum retarded the development of lesions, but this appeared to be due solely to the immune serum, suggesting no synergism between the activated reticuloendothelial system and the anti-T. pallidum antibodies. The administration of two doses of BCG enhanced syphilitic lesion development in the rabbit."} {"id": "PMID:172451", "title": "Effect of cyclophosphamide on the response of chickens to a virulent strain of Marek's disease virus.", "content": "The effect of cyclophosphamide on the pathogenesis of Marek's disease was examined in a line of chickens which is relatively resistant to Marek's disease. The injection of cyclophosphamide into newly hatched chickens delayed and reduced viremia and also reduced the development of Marek's disease lesions until 2 weeks after exposure to Marek's disease virus. The data indicate that a population of T cells susceptible to infection with virus and possibly viral transformation is affected by cyclophosphamide.", "contents": "Effect of cyclophosphamide on the response of chickens to a virulent strain of Marek's disease virus. The effect of cyclophosphamide on the pathogenesis of Marek's disease was examined in a line of chickens which is relatively resistant to Marek's disease. The injection of cyclophosphamide into newly hatched chickens delayed and reduced viremia and also reduced the development of Marek's disease lesions until 2 weeks after exposure to Marek's disease virus. The data indicate that a population of T cells susceptible to infection with virus and possibly viral transformation is affected by cyclophosphamide."} {"id": "PMID:172452", "title": "Viral replication and interferon production in fetal and adult ovine leukocytes and spleen cells.", "content": "Peripheral blood leukocyte and spleen cell cultures derived from adult sheep and from third-trimester (107 to 145 days of gestation) and second-trimester (70 to 98 days of gestation) fetal lambs were examined for their ability to support viral replication and to produce interferon. Bluetongue virus, Herpesvirus hominis type 2, and Chikungunya virus failed to replicate in either leukocyte or spleen cell cultures derived from adult ewes or in cultures from second- or third-trimester fetal lambs. Similarly, peripheral blood leukocytes from adult sheep or third-trimester fetal lambs did not support the replication of Semliki Forest virus, vesicular stomatitis virus, Newcastle disease virus, or vaccinia virus. No major differences were observed in the ability of fetal and adult leukocytes to produce interferon in response to viral infection. In contrast, mean interferon titers induced by bluetongue virus, H. hominis type 2, and Chikungunya virus in spleen cells from second-trimester fetuses were 4- to 10-fold greater than those induced in spleen cells from adult ewes. Variations in interferon levels induced on separate occasions with cells from the same donor age group were observed. The antiviral substance induced in both the fetal and adult cell cultures fulfilled the usual criteria for characterization as interferon.", "contents": "Viral replication and interferon production in fetal and adult ovine leukocytes and spleen cells. Peripheral blood leukocyte and spleen cell cultures derived from adult sheep and from third-trimester (107 to 145 days of gestation) and second-trimester (70 to 98 days of gestation) fetal lambs were examined for their ability to support viral replication and to produce interferon. Bluetongue virus, Herpesvirus hominis type 2, and Chikungunya virus failed to replicate in either leukocyte or spleen cell cultures derived from adult ewes or in cultures from second- or third-trimester fetal lambs. Similarly, peripheral blood leukocytes from adult sheep or third-trimester fetal lambs did not support the replication of Semliki Forest virus, vesicular stomatitis virus, Newcastle disease virus, or vaccinia virus. No major differences were observed in the ability of fetal and adult leukocytes to produce interferon in response to viral infection. In contrast, mean interferon titers induced by bluetongue virus, H. hominis type 2, and Chikungunya virus in spleen cells from second-trimester fetuses were 4- to 10-fold greater than those induced in spleen cells from adult ewes. Variations in interferon levels induced on separate occasions with cells from the same donor age group were observed. The antiviral substance induced in both the fetal and adult cell cultures fulfilled the usual criteria for characterization as interferon."} {"id": "PMID:172453", "title": "Neuropathological effects of persistent infection of mice by mouse hepatitis virus.", "content": "Mouse hepatitis virus (MHV3) can persist for months in strains of mice with genetically controlled \"semisusceptibility\" to this virus. The pathology of the chronic neurological disease induced in these animals has been investigated by conventional histology and immunofluorescence. A2G mice develop a chronic choroidoependymitis and meningitis leading to severe hydrocephalus and hydromyelia. In C3H mice a widespread vasculitis was observed, with both viral antigens and bound immunoglobulins in vessal walls. No significant glomerulonephritis was found. Systemic amyloidosis was present in the spleen, liver, and kidneys. The virus was not detected in neural tissues, but brain and spinal cord lesions were found near inflammatory areas surrounding damaged vessels. It is suggested that viral persistance in ependymal cells is directly responsible for the lesions in A2G mice, whereas an immunopathological lesion of blood vessels of the central nervous system underlines the damage to mice of the C3H strain.", "contents": "Neuropathological effects of persistent infection of mice by mouse hepatitis virus. Mouse hepatitis virus (MHV3) can persist for months in strains of mice with genetically controlled \"semisusceptibility\" to this virus. The pathology of the chronic neurological disease induced in these animals has been investigated by conventional histology and immunofluorescence. A2G mice develop a chronic choroidoependymitis and meningitis leading to severe hydrocephalus and hydromyelia. In C3H mice a widespread vasculitis was observed, with both viral antigens and bound immunoglobulins in vessal walls. No significant glomerulonephritis was found. Systemic amyloidosis was present in the spleen, liver, and kidneys. The virus was not detected in neural tissues, but brain and spinal cord lesions were found near inflammatory areas surrounding damaged vessels. It is suggested that viral persistance in ependymal cells is directly responsible for the lesions in A2G mice, whereas an immunopathological lesion of blood vessels of the central nervous system underlines the damage to mice of the C3H strain."} {"id": "PMID:172454", "title": "Histopathological effect of Clostridium perfringens enterotoxin in the rabbit ileum.", "content": "Highly purified enterotoxin from Clostridium perfringens was found to have histopathological activity in the rabbit ileum. Unlike the action of cholera, Escherichia coli, and Shigella enterotoxins, epithelium was denuded from the tips of ileal villi at concentrations of the enterotoxin necessary to induce fluid accumulation in the rabbit. Whether or not this observed histopathology is essential for the diarrheal syndrome associated with Clostridium perfringens food poisoning remains unclear.", "contents": "Histopathological effect of Clostridium perfringens enterotoxin in the rabbit ileum. Highly purified enterotoxin from Clostridium perfringens was found to have histopathological activity in the rabbit ileum. Unlike the action of cholera, Escherichia coli, and Shigella enterotoxins, epithelium was denuded from the tips of ileal villi at concentrations of the enterotoxin necessary to induce fluid accumulation in the rabbit. Whether or not this observed histopathology is essential for the diarrheal syndrome associated with Clostridium perfringens food poisoning remains unclear."} {"id": "PMID:172455", "title": "Monocyte activation in horses persistently infected with equine infectious anemia virus.", "content": "The monocytes of horses infected with equine infectious anemia virus were shown by their failure to migrate from capillary tubes and their increased adherence to erythrocytes to be activated.", "contents": "Monocyte activation in horses persistently infected with equine infectious anemia virus. The monocytes of horses infected with equine infectious anemia virus were shown by their failure to migrate from capillary tubes and their increased adherence to erythrocytes to be activated."} {"id": "PMID:172456", "title": "Virus-induced diabetes mellitus. V. Biological differences between the M variant and other strains of encephalomyocarditis virus.", "content": "The M variant of encephalomyocarditis virus is very closely related serologically to five other strains of encephalomyocarditis virus. Despite the serological relationship, these five viruses differ markedly from the M variant in their tissue tropisms and only the M variant infects beta cells of the pancreas, producing diabetes.", "contents": "Virus-induced diabetes mellitus. V. Biological differences between the M variant and other strains of encephalomyocarditis virus. The M variant of encephalomyocarditis virus is very closely related serologically to five other strains of encephalomyocarditis virus. Despite the serological relationship, these five viruses differ markedly from the M variant in their tissue tropisms and only the M variant infects beta cells of the pancreas, producing diabetes."} {"id": "PMID:172457", "title": "Origin of lymphoid lines established from mixed cultures of cord-blood lymphocytes and explants from infectious mononucleosis, Burkitt lymphoma and healthy donors.", "content": "Lymphocytes were explanted from EBV-seropositive donors including peripheral blood of infectious mononucleosis patients, healthy donors and EBV-genome-carrying cells from Burkitt lymphoma (BL) biopsies or nude mouse-passaged, BL-biopsy-derived lines. The explanted cells were mixed with fresh cord-blood lymphocytes from mice of the opposite sex. In all categories of derived lines, cord-blood cell progeny was predominant, as judged by the sex marker and other associated markers. Only one BL biopsy line, serially passaged in nude mice, gave rise to a monoclonal lymphoma line.", "contents": "Origin of lymphoid lines established from mixed cultures of cord-blood lymphocytes and explants from infectious mononucleosis, Burkitt lymphoma and healthy donors. Lymphocytes were explanted from EBV-seropositive donors including peripheral blood of infectious mononucleosis patients, healthy donors and EBV-genome-carrying cells from Burkitt lymphoma (BL) biopsies or nude mouse-passaged, BL-biopsy-derived lines. The explanted cells were mixed with fresh cord-blood lymphocytes from mice of the opposite sex. In all categories of derived lines, cord-blood cell progeny was predominant, as judged by the sex marker and other associated markers. Only one BL biopsy line, serially passaged in nude mice, gave rise to a monoclonal lymphoma line."} {"id": "PMID:172458", "title": "Sensitive method to detect non-complement-fixing antibodies to Epstein-Barr virus nuclear antigne.", "content": "The anti-complement immunofluorescence (ACIF) test was modified to detect non-complement-fixing antibodies to Epstein-Barr (EB) virus nuclear antigen (IBNA). These EBNA antibodies belong to the immunoglobulin classes IgA and IgG. In our method anti-human gamma-globulin (AHG) was bound to the EBNA antibodies before the complement was added. If only non-complement-fixing antibodies are present the complement can be fixed to the AHG. Within only a few weeks of the onset of infectious mononucleosis (IM) the non-complement-fixing EBNA antibodies reach high titers while the complement-fixing antibodies (detected by the ACIF test) are not yet present. Anti-EBNA-IgM antibodies were not found in the IgM fractions of sera taken at different stages of IM.", "contents": "Sensitive method to detect non-complement-fixing antibodies to Epstein-Barr virus nuclear antigne. The anti-complement immunofluorescence (ACIF) test was modified to detect non-complement-fixing antibodies to Epstein-Barr (EB) virus nuclear antigen (IBNA). These EBNA antibodies belong to the immunoglobulin classes IgA and IgG. In our method anti-human gamma-globulin (AHG) was bound to the EBNA antibodies before the complement was added. If only non-complement-fixing antibodies are present the complement can be fixed to the AHG. Within only a few weeks of the onset of infectious mononucleosis (IM) the non-complement-fixing EBNA antibodies reach high titers while the complement-fixing antibodies (detected by the ACIF test) are not yet present. Anti-EBNA-IgM antibodies were not found in the IgM fractions of sera taken at different stages of IM."} {"id": "PMID:172459", "title": "Some electrical properties of the peripheries of murine 3T3 cells with respect to viral transformation and reversion.", "content": "Mouse 3T3, Simian virus 40 transformed 3T3 cells (SV3T3) and two SV3T3 lines showing reversion of their transformed phenotype (Rev 3 and Rev 5) have been studied with respect to electrophoretic mobilities and colloidal iron hydroxide (CIH) binding density visible by electron microscopy, before and after incubation with neuraminidase or ribonuclease. The results show that, in general, the marked changes in both sets of surface parameters associated with transformation are largely reversed in the Rev 5 revertant, and only partially reversed in the Rev 3 line. It was also observed that, in common with Ehrlich ascites tumor (EAT) cells examined previously, the densities of CIH-particles bound over the microvilli of all the cell types was 1.5 to 2.7 times higher than those bound to the spaces between them. In contrast to the EAT cells, the higher density of CIH particles bound over the microvilli was not due to neuraminidase-sensitive binding sites.", "contents": "Some electrical properties of the peripheries of murine 3T3 cells with respect to viral transformation and reversion. Mouse 3T3, Simian virus 40 transformed 3T3 cells (SV3T3) and two SV3T3 lines showing reversion of their transformed phenotype (Rev 3 and Rev 5) have been studied with respect to electrophoretic mobilities and colloidal iron hydroxide (CIH) binding density visible by electron microscopy, before and after incubation with neuraminidase or ribonuclease. The results show that, in general, the marked changes in both sets of surface parameters associated with transformation are largely reversed in the Rev 5 revertant, and only partially reversed in the Rev 3 line. It was also observed that, in common with Ehrlich ascites tumor (EAT) cells examined previously, the densities of CIH-particles bound over the microvilli of all the cell types was 1.5 to 2.7 times higher than those bound to the spaces between them. In contrast to the EAT cells, the higher density of CIH particles bound over the microvilli was not due to neuraminidase-sensitive binding sites."} {"id": "PMID:172460", "title": "Studies of genetic transmission of mammary tumour virus by C3Hf mice.", "content": "By radioimmunoassay (RIA) mammary tumour virus (MTV) antigens were detected in individual milk samples of C3Hf mice, (female BALB/c X male C3Hf)F1 mice and (female C3Hf X male BALB/c)F1 mice; milk samples of BALB/c mice were negative. In the segregating backcross I population, female BALB/c X male (female BALB/c X male C3Hf) viral antigens were found in the milk of 93 out of 169 mice (55%). In the Bc II population (daughters of Bc I mothers and BALB/c fathers) two groups were distinguished. In the first group, derived from positive Bc I mothers, 55 out of 110 mice (50%) had detectable levels of viral antigens in the milk. In the second group, progeny of negative Bc I mothers, 1 mouse out of 47 was positive. These data are consistent with the assumption that one dominant gene is responsible for the presence of viral antigens in the milk of C3Hf mice. This gene (Mtv-1) seems to be linked with the albino locus situated on chromosome 7; the recombination percentage was about 29. In the first experiment with Bc I mice a significant difference was found between the tumour ages of the mice with virus-positive milk and of the mice with virus-negative milk: all mice (18) with viral antigens in the milk developed mammary tumours at an age ranging from 7 to 18 months, whereas in only 7 out of 16 mice with virus-negative milk were mammary tumours found before the age of 21 months. Viral antigens were detectable (by RIA) in the tumours of mice of both subgroups; however, the amounts (mU/mg tumour) were significantly lower in the tumours derived from mice with virus-negative milk. Although MTV-L of C3Hf mothers could be transmitted to BALB/c mice by foster-nursing, viral antigens could not be detected in milk samples collected prior to the third lactation period; thus an influence on the data of extrachromosomally transmitted MTV-L is unlikely.", "contents": "Studies of genetic transmission of mammary tumour virus by C3Hf mice. By radioimmunoassay (RIA) mammary tumour virus (MTV) antigens were detected in individual milk samples of C3Hf mice, (female BALB/c X male C3Hf)F1 mice and (female C3Hf X male BALB/c)F1 mice; milk samples of BALB/c mice were negative. In the segregating backcross I population, female BALB/c X male (female BALB/c X male C3Hf) viral antigens were found in the milk of 93 out of 169 mice (55%). In the Bc II population (daughters of Bc I mothers and BALB/c fathers) two groups were distinguished. In the first group, derived from positive Bc I mothers, 55 out of 110 mice (50%) had detectable levels of viral antigens in the milk. In the second group, progeny of negative Bc I mothers, 1 mouse out of 47 was positive. These data are consistent with the assumption that one dominant gene is responsible for the presence of viral antigens in the milk of C3Hf mice. This gene (Mtv-1) seems to be linked with the albino locus situated on chromosome 7; the recombination percentage was about 29. In the first experiment with Bc I mice a significant difference was found between the tumour ages of the mice with virus-positive milk and of the mice with virus-negative milk: all mice (18) with viral antigens in the milk developed mammary tumours at an age ranging from 7 to 18 months, whereas in only 7 out of 16 mice with virus-negative milk were mammary tumours found before the age of 21 months. Viral antigens were detectable (by RIA) in the tumours of mice of both subgroups; however, the amounts (mU/mg tumour) were significantly lower in the tumours derived from mice with virus-negative milk. Although MTV-L of C3Hf mothers could be transmitted to BALB/c mice by foster-nursing, viral antigens could not be detected in milk samples collected prior to the third lactation period; thus an influence on the data of extrachromosomally transmitted MTV-L is unlikely."} {"id": "PMID:172461", "title": "Detection of virus-specific DNA and RNA base-sequences in individual cells transformed or infected by adenovirus type 2.", "content": "By means of 3H thymidine-labelled adenovirus 2 DNA, adenovirus-specific DNA sequences have been localized in individual nuclei of adenovirus 2- or 12-infected cells, and adenovirus-specific RNA sequences have been detected in the permissive cells as well as in cells transformed by adenovirus type 2. The ability to detect such specific virus RNA base-sequences in particular, by in situ hybridization, should be useful in studying the transcriptional specificities of tumours and neoplasms.", "contents": "Detection of virus-specific DNA and RNA base-sequences in individual cells transformed or infected by adenovirus type 2. By means of 3H thymidine-labelled adenovirus 2 DNA, adenovirus-specific DNA sequences have been localized in individual nuclei of adenovirus 2- or 12-infected cells, and adenovirus-specific RNA sequences have been detected in the permissive cells as well as in cells transformed by adenovirus type 2. The ability to detect such specific virus RNA base-sequences in particular, by in situ hybridization, should be useful in studying the transcriptional specificities of tumours and neoplasms."} {"id": "PMID:172462", "title": "Radical formation in salts of pyrimidines. I. 1-methyluracil. HBr crystals.", "content": "Radicals produced by X-irradiation at 77 K of 1-methyluracil. HBr crystals have been analysed by electron spin resonance spectroscopy. The results are compared with those obtained on 1-methyluracil crystals. Four radicals have been identified, two of which are present only in 1-methyluracil. HBr crystals: the C6-addition radical and the pyrimidine--anion radical. Warming-up experiments have been performed in order to study the secondary radical reactions. The different mechanisms proposed for the radiolysis of DNA constituents in the solid state are discussed in connection with these findings.", "contents": "Radical formation in salts of pyrimidines. I. 1-methyluracil. HBr crystals. Radicals produced by X-irradiation at 77 K of 1-methyluracil. HBr crystals have been analysed by electron spin resonance spectroscopy. The results are compared with those obtained on 1-methyluracil crystals. Four radicals have been identified, two of which are present only in 1-methyluracil. HBr crystals: the C6-addition radical and the pyrimidine--anion radical. Warming-up experiments have been performed in order to study the secondary radical reactions. The different mechanisms proposed for the radiolysis of DNA constituents in the solid state are discussed in connection with these findings."} {"id": "PMID:172463", "title": "E.s.r. studies of sulphur-substituted pyrimidines. 2-thio-5-carboxyuracil at 77 K.", "content": "Single crystals of 2-thio-5-carboxyuracil were irradiated and studied at 77 K with e.s.r. spectroscopy. Five resonances were observed and related to the sulphur atom in the 2 position of the pyrimidine ring. Three of the resonances have been assigned to three conformations of a radical formed by hydrogen abstraction from N1. The principal values for the nitrogen coupling are 9-7, 0-0 and 0-0 gauss. The g tensor principal values are 2-173, 1-997 and 1-990 for the dominant conformation of this radical. Two other radicals could not be identified unambiguously.", "contents": "E.s.r. studies of sulphur-substituted pyrimidines. 2-thio-5-carboxyuracil at 77 K. Single crystals of 2-thio-5-carboxyuracil were irradiated and studied at 77 K with e.s.r. spectroscopy. Five resonances were observed and related to the sulphur atom in the 2 position of the pyrimidine ring. Three of the resonances have been assigned to three conformations of a radical formed by hydrogen abstraction from N1. The principal values for the nitrogen coupling are 9-7, 0-0 and 0-0 gauss. The g tensor principal values are 2-173, 1-997 and 1-990 for the dominant conformation of this radical. Two other radicals could not be identified unambiguously."} {"id": "PMID:172464", "title": "Ionic base radicals in gamma-irradiated oriented non-deuterated and fully deuterated DNA.", "content": "The free radicals induced by gamma-irradiation at 77 K in non-deuterated and fully deuterated oriented samples of moist algal DNA have been studied by electron paramagnetic resonance (e.p.r.). The e.p.r. spectra from the non-deuterated sample were found to be similar to those from calf-thymus DNA studied previously. Numerical spectra simulations were performed based on the previously proposed interpretation of the DNA spectra at 77 K in terms of a mixture of two spectral components arising from anionic and cationic base radicals (probably on thymine and guanine, respectively). The simulations were found to account satisfactorily for the main characteristics of the e.p.r. spectra from both the non-deuterated and the fully deuterated algal DNA sample.", "contents": "Ionic base radicals in gamma-irradiated oriented non-deuterated and fully deuterated DNA. The free radicals induced by gamma-irradiation at 77 K in non-deuterated and fully deuterated oriented samples of moist algal DNA have been studied by electron paramagnetic resonance (e.p.r.). The e.p.r. spectra from the non-deuterated sample were found to be similar to those from calf-thymus DNA studied previously. Numerical spectra simulations were performed based on the previously proposed interpretation of the DNA spectra at 77 K in terms of a mixture of two spectral components arising from anionic and cationic base radicals (probably on thymine and guanine, respectively). The simulations were found to account satisfactorily for the main characteristics of the e.p.r. spectra from both the non-deuterated and the fully deuterated algal DNA sample."} {"id": "PMID:172465", "title": "Consultation with the filipino boarding home: an after-care facility in Hawaii.", "content": "This report describes a unique Hawaiian after-care facility the Filipino operated boarding home, and the approaches useful in consultation with the operators. The majority of the boarding homes for psychiatric patients are operated by recent Filipino immigrants. This fact is explained by their current social position and also by cultural values--such as aiding others and an extended family system--which are present in the Philippines. In consultation with seventeen such boarding home operators, cultural beliefs and values played a great part in their approach to patients. These approaches created special problems and assets in their management of patients from other ethnic groups such as Japanese, Caucasian and Hawaiian. A problem-oriented approach to consultation proved useful initially and set the stage for other forms of intervention. This included allowing the operator to ventilate her feelings about the patient; bridging the communication gap between operators and patients; dissipating the operators' stereotypic perception of patients; and educating the operators about mental illness. Our impressions and indirect evidence indicated that Filipino boarding home operators perform a useful service and, with consultation sensitive to their values, can become even more effective.", "contents": "Consultation with the filipino boarding home: an after-care facility in Hawaii. This report describes a unique Hawaiian after-care facility the Filipino operated boarding home, and the approaches useful in consultation with the operators. The majority of the boarding homes for psychiatric patients are operated by recent Filipino immigrants. This fact is explained by their current social position and also by cultural values--such as aiding others and an extended family system--which are present in the Philippines. In consultation with seventeen such boarding home operators, cultural beliefs and values played a great part in their approach to patients. These approaches created special problems and assets in their management of patients from other ethnic groups such as Japanese, Caucasian and Hawaiian. A problem-oriented approach to consultation proved useful initially and set the stage for other forms of intervention. This included allowing the operator to ventilate her feelings about the patient; bridging the communication gap between operators and patients; dissipating the operators' stereotypic perception of patients; and educating the operators about mental illness. Our impressions and indirect evidence indicated that Filipino boarding home operators perform a useful service and, with consultation sensitive to their values, can become even more effective."} {"id": "PMID:172469", "title": "DNA replication in SV40-infected cells. XI. The properties of SV40 DNA and nucleoprotein complex synthesized in the presence of cycloheximide.", "content": "Cycloheximide inhibits simian virus 40 (SV40) DNA synthesis in productively infected African green monkey kidney cells. The residual viral DNA synthesized in the presence of this drug is deficient in superhelical turns as measured by band sedimentation in the presence of several concentrations of ethidium bromide. The superhelical density of SV40 DNA synthesized in the presence of cycloheximide is about one half that of viral DNA produced in the absence of this drug. Ribonuclease H and alkali treatment were employed to determine if ribonucleotides could be detected in closed circular SV40 DNA synthesized in the presence of cycloheximide. While both these approaches detected ribonucleotides in mitochondrial DNA, no identification of ribonucleotides in SV40 DNA synthesized in the presence of cycloheximide was found. The SV40 nucleoprotein complex synthesized in the presence of cycloheximide has a slower sedimentation rate (35S) and a higher bouyant density (1.54 g/cm3) than the complex made in the absence of this drug (50S; 1.47 g/cm3). The protein:DNA ratio of the SV40 nucleoprotein complex is normally about 0.9. This ratio is reduced to about 0.6 when the complex is synthesized in the presence of cycloheximide.", "contents": "DNA replication in SV40-infected cells. XI. The properties of SV40 DNA and nucleoprotein complex synthesized in the presence of cycloheximide. Cycloheximide inhibits simian virus 40 (SV40) DNA synthesis in productively infected African green monkey kidney cells. The residual viral DNA synthesized in the presence of this drug is deficient in superhelical turns as measured by band sedimentation in the presence of several concentrations of ethidium bromide. The superhelical density of SV40 DNA synthesized in the presence of cycloheximide is about one half that of viral DNA produced in the absence of this drug. Ribonuclease H and alkali treatment were employed to determine if ribonucleotides could be detected in closed circular SV40 DNA synthesized in the presence of cycloheximide. While both these approaches detected ribonucleotides in mitochondrial DNA, no identification of ribonucleotides in SV40 DNA synthesized in the presence of cycloheximide was found. The SV40 nucleoprotein complex synthesized in the presence of cycloheximide has a slower sedimentation rate (35S) and a higher bouyant density (1.54 g/cm3) than the complex made in the absence of this drug (50S; 1.47 g/cm3). The protein:DNA ratio of the SV40 nucleoprotein complex is normally about 0.9. This ratio is reduced to about 0.6 when the complex is synthesized in the presence of cycloheximide."} {"id": "PMID:172470", "title": "Cyclic appearance of defective interfering particles of herpes simplex virus and the concomitant accumulation of early polypeptide VP175.", "content": "Serial passage of undiluted herpes simplex virus types 1 and 2 resulted in cyclic production of infectious and defective virions. Defective virus production was characterized by the appearance of a new species of viral DNA with a higher bouyant density in CsCl than standard viral DNA. Measurement of the infectivity titer and DNA synthesis revealed that the defective particles interfered with the replication of standard virions and stimulated the overproduction of a large molecular weight (175,000 daltons) polypeptide.", "contents": "Cyclic appearance of defective interfering particles of herpes simplex virus and the concomitant accumulation of early polypeptide VP175. Serial passage of undiluted herpes simplex virus types 1 and 2 resulted in cyclic production of infectious and defective virions. Defective virus production was characterized by the appearance of a new species of viral DNA with a higher bouyant density in CsCl than standard viral DNA. Measurement of the infectivity titer and DNA synthesis revealed that the defective particles interfered with the replication of standard virions and stimulated the overproduction of a large molecular weight (175,000 daltons) polypeptide."} {"id": "PMID:172471", "title": "Characteristics of infection by RSV. III. Duration of the latent period in unsynchronized chick embryo fibroblasts.", "content": "The duration of the latent period of RSV was studied in unsynchronized chicken cells using two methods. First, RAV1-producing cells were infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV;subgroup D), and new virions of SR-RSV (subgroup A) produced after phenotypic mixing with RAV1 were neutralized with an antiserum to RAV1. Secondly, uninfected chicken cells were infected with SR-RSV (D) in the presence of either arabionsylcytosine, actinomycin D or cycloheximide, to inhibit the virus production. In both methods, the early decrease of the virus titer showed that new virions were produced as early as 45 min after the beginning of the infection. Earlier times were not explored.", "contents": "Characteristics of infection by RSV. III. Duration of the latent period in unsynchronized chick embryo fibroblasts. The duration of the latent period of RSV was studied in unsynchronized chicken cells using two methods. First, RAV1-producing cells were infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV;subgroup D), and new virions of SR-RSV (subgroup A) produced after phenotypic mixing with RAV1 were neutralized with an antiserum to RAV1. Secondly, uninfected chicken cells were infected with SR-RSV (D) in the presence of either arabionsylcytosine, actinomycin D or cycloheximide, to inhibit the virus production. In both methods, the early decrease of the virus titer showed that new virions were produced as early as 45 min after the beginning of the infection. Earlier times were not explored."} {"id": "PMID:172468", "title": "An analysis of factors which influence the local accumulation of bone-seeking radiopharmaceuticals.", "content": "A thoretical consideration of the factors which influence the accumulation of radiopharmaceuticals in bone is presented. The avidity with which 99mTc-Sn-pyrophosphate and 18F fluoride are adsorbed by bone crystals has been measured in vitro and the efficiency with which these radiopharmaceuticals are extracted by normal bone has been measured in vivo. It is postulated that alterations in the capillary permeability in the region of a bone lesion greatly influence the target to background ratio that can be obtained with bone seeking radiopharmaceuticals. Quantitiated gamma camera studies in man are presented in support of this hypothesis.", "contents": "An analysis of factors which influence the local accumulation of bone-seeking radiopharmaceuticals. A thoretical consideration of the factors which influence the accumulation of radiopharmaceuticals in bone is presented. The avidity with which 99mTc-Sn-pyrophosphate and 18F fluoride are adsorbed by bone crystals has been measured in vitro and the efficiency with which these radiopharmaceuticals are extracted by normal bone has been measured in vivo. It is postulated that alterations in the capillary permeability in the region of a bone lesion greatly influence the target to background ratio that can be obtained with bone seeking radiopharmaceuticals. Quantitiated gamma camera studies in man are presented in support of this hypothesis."} {"id": "PMID:172472", "title": "Polypeptide and RNA composition of the reticuloendotheliosis viruses.", "content": "The RNA and polypeptide composition of chick syncytial virus (CSV) and duck infectious anemia virus (DIAV) was investigated and compared to that of reticuloendotheliosis virus (REV) strain T, the prototype of the newly recognized REV group of viruses. CSV and DIAV contain genomic RNA species which cosediment with those of REV in sucrose gradients. Five or six polypeptides, two of which are glycoproteins, were consistently found in CSV and DIAV preparations. The major nonglycosylated polypeptides and glycoproteins of CSV and DIAV comigrated with the corresponding polypeptides of REV strain T. Since the genomic RNA species and the glycoproteins of avian tumor viruses fail to comigrate, this suggests that the REV complex is a more homogeneous group.", "contents": "Polypeptide and RNA composition of the reticuloendotheliosis viruses. The RNA and polypeptide composition of chick syncytial virus (CSV) and duck infectious anemia virus (DIAV) was investigated and compared to that of reticuloendotheliosis virus (REV) strain T, the prototype of the newly recognized REV group of viruses. CSV and DIAV contain genomic RNA species which cosediment with those of REV in sucrose gradients. Five or six polypeptides, two of which are glycoproteins, were consistently found in CSV and DIAV preparations. The major nonglycosylated polypeptides and glycoproteins of CSV and DIAV comigrated with the corresponding polypeptides of REV strain T. Since the genomic RNA species and the glycoproteins of avian tumor viruses fail to comigrate, this suggests that the REV complex is a more homogeneous group."} {"id": "PMID:172473", "title": "Spontaneous interferon production and Epstein-barr virus antigen expression in two human lymphoid cell lines and their somatic cell hybrids.", "content": "Two human lymphoid cell lines, Raji and Namalwa, and seven somatic cell hybrids between these two cells were tested for spontaneous interferon production. Namalwa and three of the hybrids produce interferon while the four other hybrids, like Raji, do not. Though the Namalwa line is relatively resistant to superinfection with the Epstein-Barr virus (EBV), all hybrids are as susceptible to EBV as the Raji parent. High extracellular concentrations of interferon likewise had little effect on EBV superinfection of Raji or the hybrid cells and it is possible that Raji produces some factor that antagonizes the action of interferon to allow virus expression.", "contents": "Spontaneous interferon production and Epstein-barr virus antigen expression in two human lymphoid cell lines and their somatic cell hybrids. Two human lymphoid cell lines, Raji and Namalwa, and seven somatic cell hybrids between these two cells were tested for spontaneous interferon production. Namalwa and three of the hybrids produce interferon while the four other hybrids, like Raji, do not. Though the Namalwa line is relatively resistant to superinfection with the Epstein-Barr virus (EBV), all hybrids are as susceptible to EBV as the Raji parent. High extracellular concentrations of interferon likewise had little effect on EBV superinfection of Raji or the hybrid cells and it is possible that Raji produces some factor that antagonizes the action of interferon to allow virus expression."} {"id": "PMID:172474", "title": "Influence of certain immunodepressants on experimental flavivirus and enterovirus infections in mice.", "content": "The effects of cyclophosphamide and 1,3-(piperidinomethyl)-5-phenyl-5-ethylbarbituric acid on certain flavi- and enterovirus infections in mice were studied. Differential enhancement of mortality rates after extraneural and, less markedly, intracerebral virus inoculation was noted. While depression of humoral and/or cell-mediated immunity is considered to be responsible for the effects observed in flavivirus infections, impaired function of the reticuloendothelial system seems to contribute mainly to the potentiation of Mengo virus infection by the immunodepressants used.", "contents": "Influence of certain immunodepressants on experimental flavivirus and enterovirus infections in mice. The effects of cyclophosphamide and 1,3-(piperidinomethyl)-5-phenyl-5-ethylbarbituric acid on certain flavi- and enterovirus infections in mice were studied. Differential enhancement of mortality rates after extraneural and, less markedly, intracerebral virus inoculation was noted. While depression of humoral and/or cell-mediated immunity is considered to be responsible for the effects observed in flavivirus infections, impaired function of the reticuloendothelial system seems to contribute mainly to the potentiation of Mengo virus infection by the immunodepressants used."} {"id": "PMID:172478", "title": "Observations on ambulatory electrocardiographic monitoring in clinical practice.", "content": "Holter monitoring is a practical technique for determining rate, rhythm, contour, and conduction changes in the electrocardiogram of the ambulatory patient. This kind of information may be of great clinical importance in coronary artery disease with or without myocardial infarction, in patients with permanent pacemakers, in the presence of central nervous system symptoms, and perhaps in patients with chronic obstructive pulmonary disease. Correlating ambulatory electrocardiographic findings in patients with these diseases and syndromes provides insight into the severity of the process involved. It may also define the response to therapy and to specific social and work situations. Present instrumentation, although reasonably effective, may be considered in an early developmental stage. Future progress in terms of miniaturization, automatic patient warning systems, and activation of central recording units, may further broaden the implications for ambulatory electrocardiographic monitoring. The scope of these observations and the variety of unsuspected rhythm and contour abnormalities defined may ultimately rival the information gained in monitored hospitalized patients. It is hoped that this information will have an impact on the therapy of the ambulatory patient comparable to that which coronary-care unit monitoring has had on the hospitalized patient with acute myocardial infarction.", "contents": "Observations on ambulatory electrocardiographic monitoring in clinical practice. Holter monitoring is a practical technique for determining rate, rhythm, contour, and conduction changes in the electrocardiogram of the ambulatory patient. This kind of information may be of great clinical importance in coronary artery disease with or without myocardial infarction, in patients with permanent pacemakers, in the presence of central nervous system symptoms, and perhaps in patients with chronic obstructive pulmonary disease. Correlating ambulatory electrocardiographic findings in patients with these diseases and syndromes provides insight into the severity of the process involved. It may also define the response to therapy and to specific social and work situations. Present instrumentation, although reasonably effective, may be considered in an early developmental stage. Future progress in terms of miniaturization, automatic patient warning systems, and activation of central recording units, may further broaden the implications for ambulatory electrocardiographic monitoring. The scope of these observations and the variety of unsuspected rhythm and contour abnormalities defined may ultimately rival the information gained in monitored hospitalized patients. It is hoped that this information will have an impact on the therapy of the ambulatory patient comparable to that which coronary-care unit monitoring has had on the hospitalized patient with acute myocardial infarction."} {"id": "PMID:172481", "title": "Tracer and freeze-etching analysis of intra-cellular membrane-junctions in Paramecium with a note on a new heme-nonapeptide tracer.", "content": "In paramecia the membranes of alveoli and trichocysts are permanently connected to the cell membrane by membrane-junctions, which consist of membrane-intercalated particles in a regular geometrical arrangement. Trichocysts contain secretory material discharged by exocytosis. In unfixed or fixed cells these two compartments were impermeable to the following tracers: To \"microperoxidases\", i.e. a cytochrome c-derived heme-nonapeptide and a heme-undecapeptide (WM approximately 1650, 1900) applied in vivo, as well as to lanthanum and cytochrome c used during (La) or after (cytochrome c) fixation. The heme-nonapeptide was prepared by TPCK trypsin digestion of cytochrome c and subsequent purification by Sephadex gel chromatography--a simple and inexpensive new procedure resulting in preparations of high yield and purity. Tracers entered alveoli only when the plasmalemma and the alveolar membranes ruptured upon glutardialdehyde fixation. In no case were transmembraneous channels detectable in regions containing membrane-intercalated particles; this holds true for all tracers used and for freeze-fracture replicas obtained by tantalum-tungsten evaporation. With regard to attachment sites over trichocysts our results do not support the assumptions by others according to which exocytosis would be driven by an osmotic shift via transmembraneous channels (which would be analogous to inter-cellular coupling phenomena mediated by gap-junctions), unless such channels would be assumed to operate as carriers rather than via diffusion. Tracers did not penetrate trichocysts before exocytosis occurred. The functional role of membrane-intercalated particles on trichocyst attachments remains unclear. Despite some resemblance with gap-junctions all types of intra-cellular membrane-junctions investigated are functionally \"tight\" at the level of \"resolution\" obtained with tantalumtungsten-shadowing and with the tracers used.", "contents": "Tracer and freeze-etching analysis of intra-cellular membrane-junctions in Paramecium with a note on a new heme-nonapeptide tracer. In paramecia the membranes of alveoli and trichocysts are permanently connected to the cell membrane by membrane-junctions, which consist of membrane-intercalated particles in a regular geometrical arrangement. Trichocysts contain secretory material discharged by exocytosis. In unfixed or fixed cells these two compartments were impermeable to the following tracers: To \"microperoxidases\", i.e. a cytochrome c-derived heme-nonapeptide and a heme-undecapeptide (WM approximately 1650, 1900) applied in vivo, as well as to lanthanum and cytochrome c used during (La) or after (cytochrome c) fixation. The heme-nonapeptide was prepared by TPCK trypsin digestion of cytochrome c and subsequent purification by Sephadex gel chromatography--a simple and inexpensive new procedure resulting in preparations of high yield and purity. Tracers entered alveoli only when the plasmalemma and the alveolar membranes ruptured upon glutardialdehyde fixation. In no case were transmembraneous channels detectable in regions containing membrane-intercalated particles; this holds true for all tracers used and for freeze-fracture replicas obtained by tantalum-tungsten evaporation. With regard to attachment sites over trichocysts our results do not support the assumptions by others according to which exocytosis would be driven by an osmotic shift via transmembraneous channels (which would be analogous to inter-cellular coupling phenomena mediated by gap-junctions), unless such channels would be assumed to operate as carriers rather than via diffusion. Tracers did not penetrate trichocysts before exocytosis occurred. The functional role of membrane-intercalated particles on trichocyst attachments remains unclear. Despite some resemblance with gap-junctions all types of intra-cellular membrane-junctions investigated are functionally \"tight\" at the level of \"resolution\" obtained with tantalumtungsten-shadowing and with the tracers used."} {"id": "PMID:172482", "title": "Septamycin, a polyether antibiotic. Taxonomy, fermentation, isolation and characterization.", "content": "Septamycin is a metal complexing polyether antibiotic produced by a strain of Streptomyces hygroscopicus NRRL 5678. The metabolite, a monocarboxylic acid, was isolated as the sodium salt C48H81NaO16. The crystal structure and absolute configuration were established by X-ray analysis of the p-bromophenacyl derivative. Septamycin has a thirty-carbon backbone and contains seven heterocyclic rings. Supported by direct comparison septamycin proved to be identical with antibiotic A28695 A isolated from Streptomyces albus NRRL 3883. The metabolite is active against gram-positive bacteria and Eimeria tenella (chicken coccidiosis).", "contents": "Septamycin, a polyether antibiotic. Taxonomy, fermentation, isolation and characterization. Septamycin is a metal complexing polyether antibiotic produced by a strain of Streptomyces hygroscopicus NRRL 5678. The metabolite, a monocarboxylic acid, was isolated as the sodium salt C48H81NaO16. The crystal structure and absolute configuration were established by X-ray analysis of the p-bromophenacyl derivative. Septamycin has a thirty-carbon backbone and contains seven heterocyclic rings. Supported by direct comparison septamycin proved to be identical with antibiotic A28695 A isolated from Streptomyces albus NRRL 3883. The metabolite is active against gram-positive bacteria and Eimeria tenella (chicken coccidiosis)."} {"id": "PMID:172486", "title": "Brevibacterium liquefaciens adenylate cyclase and its in vivo stimulation by pyruvate.", "content": "Adenylate cyclase of Brevibacterium liquefaciens depends on pyruvate for activity. Growing in a simple medium containing glucose and DL-alanine, the microorganism excreted pyruvate, which reached 20 mM in the medium at stationary phase. Using [3H]adenosine to label the adenosine 5'-triphosphate pool, we showed that pyruvate in the medium stimulated adenylate cyclase of B. liquefaciens in vivo, in a manner similar to the stimulation observed in vitro. Adenylate cyclase in cells harvested at different phases of growth was equally responsive to exogenous pyruvate, indicating that the allosteric site for pyruvate was present in the enzyme throughout the various phases of cell growth. The specific activity of adenylate cyclase was highest in cells harvested at early log phase; thereafter it declined and was substantially lower at stationary phase. Although adenylate cyclase appears to be activated by pyruvate throughout the life span of the cell, the activity appears not to be critical to cell growth, which was comparable whether the medium contained high or low pyruvate.", "contents": "Brevibacterium liquefaciens adenylate cyclase and its in vivo stimulation by pyruvate. Adenylate cyclase of Brevibacterium liquefaciens depends on pyruvate for activity. Growing in a simple medium containing glucose and DL-alanine, the microorganism excreted pyruvate, which reached 20 mM in the medium at stationary phase. Using [3H]adenosine to label the adenosine 5'-triphosphate pool, we showed that pyruvate in the medium stimulated adenylate cyclase of B. liquefaciens in vivo, in a manner similar to the stimulation observed in vitro. Adenylate cyclase in cells harvested at different phases of growth was equally responsive to exogenous pyruvate, indicating that the allosteric site for pyruvate was present in the enzyme throughout the various phases of cell growth. The specific activity of adenylate cyclase was highest in cells harvested at early log phase; thereafter it declined and was substantially lower at stationary phase. Although adenylate cyclase appears to be activated by pyruvate throughout the life span of the cell, the activity appears not to be critical to cell growth, which was comparable whether the medium contained high or low pyruvate."} {"id": "PMID:172487", "title": "Operator-constitutive mutants in the threonine operon of Escherichia coli K-12.", "content": "Three Escherichia coli K-12 mutant strains resistant to DL-alpha-amino-beta-hydroxyvaleric acid were isolated in which the expression of the thr operon is constitutive. The localization and dominance properties of the mutations involved, called thrO, are those of operator mutations. The gene sequence is OABC as suggested by earlier studies.", "contents": "Operator-constitutive mutants in the threonine operon of Escherichia coli K-12. Three Escherichia coli K-12 mutant strains resistant to DL-alpha-amino-beta-hydroxyvaleric acid were isolated in which the expression of the thr operon is constitutive. The localization and dominance properties of the mutations involved, called thrO, are those of operator mutations. The gene sequence is OABC as suggested by earlier studies."} {"id": "PMID:172488", "title": "Electron-transferring flavoprotein of Peptostreptococcus elsdenii that functions in the reduction of acrylyl-coenzyme A.", "content": "In Peptostreptococcus elsdenii, a three-component flavoprotein electron transfer system catalyzes the oxidation of lactate and the reduction of crotonyl-coenzyme A (CoA). Spectral evidence showed that D-lactate dehydrogenase, when reduced by D-lactate, was able to reduce butyryl-CoA dehydrogenase, but only in the presence of the electron-transferring flavoprotein. Reduced nicotinamide adenine dinucleotide could replace reduced D-lactate dehydrogenase. A reconstituted system, containing the three partially purified enzymes, excess D-lactate, and a limiting amount of crotonyl-CoA, reduced the crotonyl-CoA to butyryl-CoA, but only if all components were present. The electron-transferring flavoprotein activity, purified 22-fold, was separated into two major flavoprotein components, A and B, after polyacrylamide gel electrophoresis. Elution of the proteins and subsequent kinetic assays of the eluates showed that component B catalyzes the reduction of butyryl-CoA dehydrogenase by reduced D-lactate dehydrogenase, whereas component A does not. Both A and B catalyzed the reduction of butyryl-CoA dehydrogenase by reduced nicotinamide adenine dinucleotide. The results suggest that the D-lactate dehydrogenase-dependent reduction involves a heretofore unrecognized component of the electron-transferring protein group which may utilize an unusual flavin, 6-hydroxy-7,8-dimethyl-10-(ribityl-5'-adenosine diphosphate)-isoalloxazine.", "contents": "Electron-transferring flavoprotein of Peptostreptococcus elsdenii that functions in the reduction of acrylyl-coenzyme A. In Peptostreptococcus elsdenii, a three-component flavoprotein electron transfer system catalyzes the oxidation of lactate and the reduction of crotonyl-coenzyme A (CoA). Spectral evidence showed that D-lactate dehydrogenase, when reduced by D-lactate, was able to reduce butyryl-CoA dehydrogenase, but only in the presence of the electron-transferring flavoprotein. Reduced nicotinamide adenine dinucleotide could replace reduced D-lactate dehydrogenase. A reconstituted system, containing the three partially purified enzymes, excess D-lactate, and a limiting amount of crotonyl-CoA, reduced the crotonyl-CoA to butyryl-CoA, but only if all components were present. The electron-transferring flavoprotein activity, purified 22-fold, was separated into two major flavoprotein components, A and B, after polyacrylamide gel electrophoresis. Elution of the proteins and subsequent kinetic assays of the eluates showed that component B catalyzes the reduction of butyryl-CoA dehydrogenase by reduced D-lactate dehydrogenase, whereas component A does not. Both A and B catalyzed the reduction of butyryl-CoA dehydrogenase by reduced nicotinamide adenine dinucleotide. The results suggest that the D-lactate dehydrogenase-dependent reduction involves a heretofore unrecognized component of the electron-transferring protein group which may utilize an unusual flavin, 6-hydroxy-7,8-dimethyl-10-(ribityl-5'-adenosine diphosphate)-isoalloxazine."} {"id": "PMID:172489", "title": "Multiple regulatory events in the development of competence for genetic transformation in Haemophilus influenzae.", "content": "Cyclic adenosine 3',5'-monophosphate derepresses enzyme synthesis but does not yield high levels of transformability or detectable levels of competence-related envelope polypeptides. Additional regulatory events must trigger complete expression of competence.", "contents": "Multiple regulatory events in the development of competence for genetic transformation in Haemophilus influenzae. Cyclic adenosine 3',5'-monophosphate derepresses enzyme synthesis but does not yield high levels of transformability or detectable levels of competence-related envelope polypeptides. Additional regulatory events must trigger complete expression of competence."} {"id": "PMID:172490", "title": "Competitive inhibition of transformation in group H Streptococcus strain Challis by heterologous deoxyribonucleic acid.", "content": "Glucosylated deoxyribonucleic acid (DNA) from phages T4 and T6 competes poorly with homologous DNA causing only a slight decrease of transformation in Group H Streptococcus strain Challis. Other types of heterologous DNAs (Micrococcus luteus, Clostridium perfringens, Escherichia coli, calf thymus and non-glucosylated phage T6 DNA), in contrast to glucosylated T4 and T6 DNAs, compete with transforming DNA to the normal, high extent. These results indicate that as in transformation of Bacillus subtilis, the presence of glucose attached to 5-hydroxymethylcytosine in phage T6 DNA considerably decreases the interaction of such DNA with competent cells of the Challis strain. It also indicates that the guanine plus cytosine content of DNA is not decisive in determining its interaction with competent cells.", "contents": "Competitive inhibition of transformation in group H Streptococcus strain Challis by heterologous deoxyribonucleic acid. Glucosylated deoxyribonucleic acid (DNA) from phages T4 and T6 competes poorly with homologous DNA causing only a slight decrease of transformation in Group H Streptococcus strain Challis. Other types of heterologous DNAs (Micrococcus luteus, Clostridium perfringens, Escherichia coli, calf thymus and non-glucosylated phage T6 DNA), in contrast to glucosylated T4 and T6 DNAs, compete with transforming DNA to the normal, high extent. These results indicate that as in transformation of Bacillus subtilis, the presence of glucose attached to 5-hydroxymethylcytosine in phage T6 DNA considerably decreases the interaction of such DNA with competent cells of the Challis strain. It also indicates that the guanine plus cytosine content of DNA is not decisive in determining its interaction with competent cells."} {"id": "PMID:172491", "title": "Purification and some properties of cytochrome c-552 from a sulfur-oxidizing bacterium, Thiobacillus thiooxidans.", "content": "A soluble cytochrome c-552 from Thiobacillus thiooxidans was highly purified and its physico-chemical properteis were studied. The absorption maxima were at 552,523,418 nm in the reduced from and at 412 nm in the oxidized form. The pyridine hemochrome spectrum was the same as that of other cytochromes c. The molecular weight, estimated by the gel filtration method, was found to be 12,600. The isoelectric point was determined to be 9.2-9.3 by the electrofocusing technique. The standard oxidation-reduction potential of this cytochrome was +0.247 V.", "contents": "Purification and some properties of cytochrome c-552 from a sulfur-oxidizing bacterium, Thiobacillus thiooxidans. A soluble cytochrome c-552 from Thiobacillus thiooxidans was highly purified and its physico-chemical properteis were studied. The absorption maxima were at 552,523,418 nm in the reduced from and at 412 nm in the oxidized form. The pyridine hemochrome spectrum was the same as that of other cytochromes c. The molecular weight, estimated by the gel filtration method, was found to be 12,600. The isoelectric point was determined to be 9.2-9.3 by the electrofocusing technique. The standard oxidation-reduction potential of this cytochrome was +0.247 V."} {"id": "PMID:172492", "title": "Purification of homogeneous glutamine-dependent carbamyl phosphate synthetase from ascites hepatoma cells as a complex with aspartate transcarbamylase and dihydroorotase.", "content": "Glutamine-dependent carbamyl phosphate synthetase [EC 2.7.2.9] was purified 1,300-fold from rat ascites hepatoma cells (AH 13) as a multienzyme complex with aspartate transcarbamylase[EC 2.1.3.2] and dihydroorotase[EC 3.5.2.3], using dimethyl sulfoxide, glycerol, and dithiothreitol as stabilizers. The purified complex was essentially homogeneous on agarose-acrylamide composite gel electrophoresis and analytical ultracentrifugation. Its molecular weight was estimated to be about 870,000 by sedimentation equilibrium studies. After alkylation with iodoacetamide or reduction with 0.6% dithiothreitol at 100 degrees, the complex gave a single band on polyacrylamide gel electrophoresis in sodium dodecyl sulfate in a position corresponding to a molecular weight of 210,000. These results indicate that the complex consists of four subunits of similar size.", "contents": "Purification of homogeneous glutamine-dependent carbamyl phosphate synthetase from ascites hepatoma cells as a complex with aspartate transcarbamylase and dihydroorotase. Glutamine-dependent carbamyl phosphate synthetase [EC 2.7.2.9] was purified 1,300-fold from rat ascites hepatoma cells (AH 13) as a multienzyme complex with aspartate transcarbamylase[EC 2.1.3.2] and dihydroorotase[EC 3.5.2.3], using dimethyl sulfoxide, glycerol, and dithiothreitol as stabilizers. The purified complex was essentially homogeneous on agarose-acrylamide composite gel electrophoresis and analytical ultracentrifugation. Its molecular weight was estimated to be about 870,000 by sedimentation equilibrium studies. After alkylation with iodoacetamide or reduction with 0.6% dithiothreitol at 100 degrees, the complex gave a single band on polyacrylamide gel electrophoresis in sodium dodecyl sulfate in a position corresponding to a molecular weight of 210,000. These results indicate that the complex consists of four subunits of similar size."} {"id": "PMID:172493", "title": "Role of ubiquinone-10 in electron transport system of chromatophores from Rhodospirillum rubrum.", "content": "The role of ubiquinone-10 in the activities for the reduction of free cytochrome c2 and bound cytochrome cc' by succinate was studied with chromatophores from a blue-green mutant (G-9) of Rhodospirillum rubrum. 1. By a single extraction with isooctane, approximately 90% of ubiquinone-10 was easily removed from the chromatophores. In the extracted chromatophores, the activity for succinate-cytochrome c2 reduction decreased to 5-10% of the original activity. This depressed activity was mostly restored by adding ubiquinone-10. The remaining quinone was hardly extractable, even by repeated extractions. With repeatedly extracted chromatophores, the activity for succinate-cytochrome c2 reduction was mostly restored to the same extent as with once-extracted chromatophores, whereas the extent of inhibtion of the activity by antimycin A gradually fell. 2. In isooctane-extracted chromatophores, the activity for the reduction of bound cytochrome cc' by succinate under anaerobic conditions decreased to 35 to 95% of the original level. With chromatophores in which the remaining activity was as low as 40% of the original level, the activity was partially restored by adding ubiquinone-10, but this was not the case with chromatophores in which the remaining activity was higher than approximately 50% of the original level.", "contents": "Role of ubiquinone-10 in electron transport system of chromatophores from Rhodospirillum rubrum. The role of ubiquinone-10 in the activities for the reduction of free cytochrome c2 and bound cytochrome cc' by succinate was studied with chromatophores from a blue-green mutant (G-9) of Rhodospirillum rubrum. 1. By a single extraction with isooctane, approximately 90% of ubiquinone-10 was easily removed from the chromatophores. In the extracted chromatophores, the activity for succinate-cytochrome c2 reduction decreased to 5-10% of the original activity. This depressed activity was mostly restored by adding ubiquinone-10. The remaining quinone was hardly extractable, even by repeated extractions. With repeatedly extracted chromatophores, the activity for succinate-cytochrome c2 reduction was mostly restored to the same extent as with once-extracted chromatophores, whereas the extent of inhibtion of the activity by antimycin A gradually fell. 2. In isooctane-extracted chromatophores, the activity for the reduction of bound cytochrome cc' by succinate under anaerobic conditions decreased to 35 to 95% of the original level. With chromatophores in which the remaining activity was as low as 40% of the original level, the activity was partially restored by adding ubiquinone-10, but this was not the case with chromatophores in which the remaining activity was higher than approximately 50% of the original level."} {"id": "PMID:172494", "title": "Characterization of two soluble ferredoxins as distinct from bound iron-sulfur proteins in the photosynthetic bacterium Rhodospirillum rubrum.", "content": "In an earlier investigation (Shanmugam, K. T., Buchanan, B. B., and Arnon, D. I. (1972) Biochim. Biophys. Acta 256, 477-486) the extraction of ferredoxin from Rhodospirillum rubrum cells with the aid of a detergent (Triton X-100) and acetone revealed the existence of two types of ferredoxin (I and II) and led to the conclusion that both are membrane-bound. In the present investigation, ferredoxin and acid-labile sulfur analyses of photosynthetic membranes (chromatophores) and soluble protein extracts of the photosynthetic bacteria R. rubrum and Rhodopseudomonas spheroides showed that ferredoxins I and II are primarily components of the soluble protein fraction. After their removal, washed R. rubrum chromatophores were found to contain a considerable amount of tightly bound iron-sulfur protein(s), as evidenced by acid-labile sulfur and electron paramagnetic resonance analyses. Thus, like all other photosynthetic cells examined to date, R. rubrum cells contain both soluble ferredoxins and iron-sulfur proteins tightly bound to photosynthetic membranes. The molecular weights of ferredoxins I and II from photosynthetically grown R. rubrum cells were found to be 8,800 and 14,500, respectively. Using these molecular weights, the molar extinction coefficients at 390 nm for ferredoxins I and II were determined to be 30.3 and 17.2 mM-1 CM-1, respectively. Ferredoxin I contains 8 non-heme iron and 8 acid-labile sulfur atoms per molecule; ferredoxin II contains 4 non-heme iron and 4 acid-labile sulfur atoms per molecule. Ferredoxin I was found only in photosynthetically grown cells whereas ferredoxin II was present in both light- and dark-grown cells. Ferredoxin II from both light- and dark-grown cells has the same molecular weight (14,500) and absorption spectrum and has 4 iron and 4 acid-labile sulfur atoms per molecule. Low temperature electron paramagnetic resonance spectra of oxidized and photoreduced ferredoxins I and II from R. rubrum were recorded. The EPR spectrum of oxidized ferredoxin II exhibited a single resonance line at g = 2.012. Oxidized ferredoxin I, however, exhibited a spectrum that may arise from the superimposition of two resonance lines near g = 2.012. Photoreduced ferredoxin II displayed a rhombic EPR spectrum with a g value of 1.94. Photoreduced ferredoxin I exhibited a similar EPR spectrum at a temperature of 16 K, but when the temperature was lowered to 4.5 K the spectrum of ferredoxin I changed. This temperature-dependent spectrum may result from a weak spin-spin interaction between two iron-sulfur clusters. These results are consistent with the conclusion that R. rubrum ferredoxins I and II are, respectively, 8 iron/8 sulfur and 4 iron/4sulfur proteins.", "contents": "Characterization of two soluble ferredoxins as distinct from bound iron-sulfur proteins in the photosynthetic bacterium Rhodospirillum rubrum. In an earlier investigation (Shanmugam, K. T., Buchanan, B. B., and Arnon, D. I. (1972) Biochim. Biophys. Acta 256, 477-486) the extraction of ferredoxin from Rhodospirillum rubrum cells with the aid of a detergent (Triton X-100) and acetone revealed the existence of two types of ferredoxin (I and II) and led to the conclusion that both are membrane-bound. In the present investigation, ferredoxin and acid-labile sulfur analyses of photosynthetic membranes (chromatophores) and soluble protein extracts of the photosynthetic bacteria R. rubrum and Rhodopseudomonas spheroides showed that ferredoxins I and II are primarily components of the soluble protein fraction. After their removal, washed R. rubrum chromatophores were found to contain a considerable amount of tightly bound iron-sulfur protein(s), as evidenced by acid-labile sulfur and electron paramagnetic resonance analyses. Thus, like all other photosynthetic cells examined to date, R. rubrum cells contain both soluble ferredoxins and iron-sulfur proteins tightly bound to photosynthetic membranes. The molecular weights of ferredoxins I and II from photosynthetically grown R. rubrum cells were found to be 8,800 and 14,500, respectively. Using these molecular weights, the molar extinction coefficients at 390 nm for ferredoxins I and II were determined to be 30.3 and 17.2 mM-1 CM-1, respectively. Ferredoxin I contains 8 non-heme iron and 8 acid-labile sulfur atoms per molecule; ferredoxin II contains 4 non-heme iron and 4 acid-labile sulfur atoms per molecule. Ferredoxin I was found only in photosynthetically grown cells whereas ferredoxin II was present in both light- and dark-grown cells. Ferredoxin II from both light- and dark-grown cells has the same molecular weight (14,500) and absorption spectrum and has 4 iron and 4 acid-labile sulfur atoms per molecule. Low temperature electron paramagnetic resonance spectra of oxidized and photoreduced ferredoxins I and II from R. rubrum were recorded. The EPR spectrum of oxidized ferredoxin II exhibited a single resonance line at g = 2.012. Oxidized ferredoxin I, however, exhibited a spectrum that may arise from the superimposition of two resonance lines near g = 2.012. Photoreduced ferredoxin II displayed a rhombic EPR spectrum with a g value of 1.94. Photoreduced ferredoxin I exhibited a similar EPR spectrum at a temperature of 16 K, but when the temperature was lowered to 4.5 K the spectrum of ferredoxin I changed. This temperature-dependent spectrum may result from a weak spin-spin interaction between two iron-sulfur clusters. These results are consistent with the conclusion that R. rubrum ferredoxins I and II are, respectively, 8 iron/8 sulfur and 4 iron/4sulfur proteins."} {"id": "PMID:172495", "title": "Function of sulfhydryl groups in ribosome-elongation factor G reactions. Assignment of guanine nucleotide binding site to elongation factor G.", "content": "Titration of elongation factor G (EF-G) with the thiol reagents 5,5'-dithiobis(2-nitrobenzoate) (DNTB), p-hydroxymercuribenzoate (HMB), and N-ethylmaleimide and analysis of cysteic acid after performic acid oxidation revealed a total of four sulfhydryl groups per EF-G molecule. One of these is exposed in the native state and could be used to distinguish between two different conformations of EF-G in our preparations according to its rate of reaction with DTNB and HMB. No evidence for disulfide bridges was obtained. Among the different nucleotides tested, GTP, GDP, and GMP were able to protect the native sulfhydryl group against reaction with DTNB in the absence of ribosomes. Their Kd values with the faster reacting EF-G were 3.4 x 10(-4) M, 0.3 X 10(-4)M, and 2.0 x 10(-4) M, respectively. Because of the specificity of protection by guanine nucleotides and the correspondence of the Kd values with Ki values for GDP and GMP in the ribosome-EF-G GTPase reaction, their binding site on EF-G should be closely related to the active center for ribosome-dependent GTP hydrolysis. Blockage of the native sulfhydryl group of EF-G with a variety of irreversible thiol reagents reduced its activity from one to two-thirds in ribosome-dependent complex formation, GTP hydrolysis, and poly(U)-directed poly(phenylalanine) synthesis. A test of the N-ethylmaleimide-treated EF-G showed both the Km and Vmax of the GTPase reaction to be affected. Thus, the native sulfhydryl group, although important, appears not to be located in the GTPase active center. Denaturation of EF-G with guanidine-HCl and random blockage of any of the three masked sulfhydryl groups caused inactivation, likely due to steric interference with proper chain folding upon renaturation. Treatment of ribosomes or ribosomal subunits with six different thiol reagents at a concentration of 0.27 mM had little or no effect on the ribosome-EF-G GTPase, except for the case with HMB which inactivated the 30 S subunit. An interaction of EF-G with the 30 S subunit in addition to that known to occur with the 50 S subunit is suggested by a rapid and preferential exchange of HMB from the native sulfhydryl group of EF-G to the 30 S subunit of 70 S ribosomes.", "contents": "Function of sulfhydryl groups in ribosome-elongation factor G reactions. Assignment of guanine nucleotide binding site to elongation factor G. Titration of elongation factor G (EF-G) with the thiol reagents 5,5'-dithiobis(2-nitrobenzoate) (DNTB), p-hydroxymercuribenzoate (HMB), and N-ethylmaleimide and analysis of cysteic acid after performic acid oxidation revealed a total of four sulfhydryl groups per EF-G molecule. One of these is exposed in the native state and could be used to distinguish between two different conformations of EF-G in our preparations according to its rate of reaction with DTNB and HMB. No evidence for disulfide bridges was obtained. Among the different nucleotides tested, GTP, GDP, and GMP were able to protect the native sulfhydryl group against reaction with DTNB in the absence of ribosomes. Their Kd values with the faster reacting EF-G were 3.4 x 10(-4) M, 0.3 X 10(-4)M, and 2.0 x 10(-4) M, respectively. Because of the specificity of protection by guanine nucleotides and the correspondence of the Kd values with Ki values for GDP and GMP in the ribosome-EF-G GTPase reaction, their binding site on EF-G should be closely related to the active center for ribosome-dependent GTP hydrolysis. Blockage of the native sulfhydryl group of EF-G with a variety of irreversible thiol reagents reduced its activity from one to two-thirds in ribosome-dependent complex formation, GTP hydrolysis, and poly(U)-directed poly(phenylalanine) synthesis. A test of the N-ethylmaleimide-treated EF-G showed both the Km and Vmax of the GTPase reaction to be affected. Thus, the native sulfhydryl group, although important, appears not to be located in the GTPase active center. Denaturation of EF-G with guanidine-HCl and random blockage of any of the three masked sulfhydryl groups caused inactivation, likely due to steric interference with proper chain folding upon renaturation. Treatment of ribosomes or ribosomal subunits with six different thiol reagents at a concentration of 0.27 mM had little or no effect on the ribosome-EF-G GTPase, except for the case with HMB which inactivated the 30 S subunit. An interaction of EF-G with the 30 S subunit in addition to that known to occur with the 50 S subunit is suggested by a rapid and preferential exchange of HMB from the native sulfhydryl group of EF-G to the 30 S subunit of 70 S ribosomes."} {"id": "PMID:172496", "title": "Structural requirements for the interaction of 1 alpha, 25-(OH) 2- vitiamin D3 with its chick interestinal receptor system.", "content": "The mechanism by which 1 alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3), the biologically active metabolite of cholecalciferol (vitamin D3), stimulates intestinal calcium absorption has been shown to involve an interaction of the steroid with a specific cytosol-chromatin receptor system in this target organ. Thus, 1alpha,12(OH)2D3 binds to a specific cytoplasmic receptor protein and then, following a temperature-dependent step, becomes associated with a finite number of chromatin acceptor sites prior to the initiation of the physiological response. In this respect, 1alpha,25(OH) 2D3 is similar to a number of other steroid hormones. In this investigation, studies were performed to help define the essential structural features required for interaction of 1alpha,25-(OH)2D3 with its intestinal receptor system, and presumably, for biological activity. To this end, competition studies utilizing a series of closely related structural analogs of cholecalciferol were carried out by means of a competitive binding assay highly specific for 1alpha,25(OH)2D3. The competitive binding assay employed in this study is dependent upon the ability to duplicate, in vitro, the conditions which permit the saturable binding of 1alpha,25-(OH)2[3H]D3 to chick intestinal chromatin, in vivo. Optimal conditions for this assay were achieved by the incubation of a reconstituted intestinal receptor system consisting of separately isolated cytosol and Triton X-100 chromatin fractions at 25 degrees for 45 min with 2.0 X 10-8 M 1alpha,25-(OH)2[3H]D3. Maximal binding of about 21 to 24 pmol of radioactive steroid bound per chick intestinal chromatin occurred under these conditions. The ability of the various analogs to compete with the radioactive hormone was assessed by virtue of a decrease in the amount of radioactive steroid bound to the chromatin in the presence of increasing concentrations of nonradioactive analog.", "contents": "Structural requirements for the interaction of 1 alpha, 25-(OH) 2- vitiamin D3 with its chick interestinal receptor system. The mechanism by which 1 alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3), the biologically active metabolite of cholecalciferol (vitamin D3), stimulates intestinal calcium absorption has been shown to involve an interaction of the steroid with a specific cytosol-chromatin receptor system in this target organ. Thus, 1alpha,12(OH)2D3 binds to a specific cytoplasmic receptor protein and then, following a temperature-dependent step, becomes associated with a finite number of chromatin acceptor sites prior to the initiation of the physiological response. In this respect, 1alpha,25(OH) 2D3 is similar to a number of other steroid hormones. In this investigation, studies were performed to help define the essential structural features required for interaction of 1alpha,25-(OH)2D3 with its intestinal receptor system, and presumably, for biological activity. To this end, competition studies utilizing a series of closely related structural analogs of cholecalciferol were carried out by means of a competitive binding assay highly specific for 1alpha,25(OH)2D3. The competitive binding assay employed in this study is dependent upon the ability to duplicate, in vitro, the conditions which permit the saturable binding of 1alpha,25-(OH)2[3H]D3 to chick intestinal chromatin, in vivo. Optimal conditions for this assay were achieved by the incubation of a reconstituted intestinal receptor system consisting of separately isolated cytosol and Triton X-100 chromatin fractions at 25 degrees for 45 min with 2.0 X 10-8 M 1alpha,25-(OH)2[3H]D3. Maximal binding of about 21 to 24 pmol of radioactive steroid bound per chick intestinal chromatin occurred under these conditions. The ability of the various analogs to compete with the radioactive hormone was assessed by virtue of a decrease in the amount of radioactive steroid bound to the chromatin in the presence of increasing concentrations of nonradioactive analog."} {"id": "PMID:172497", "title": "Binding and degradation of 125I-insulin by rat hepatocytes.", "content": "The binding and the velocity of degradation of 125I-insulin in the absence or presence of varying concentrations of native procline insulin were studied using isolated rat hepatocytes. At insulin concentrations ranging from 5 X 10(-11) to 10(-6) M, insulin degradation velocity showed a first order dependence on the total concentration of insulin bound at steady state. The overall reaction had an apparent rate constant of 0.030 +/- 0.011 min-1. Furthermore, the degradation of a given amount of 125I-insulin bound to cells was more rapid and extensive than the degradation of the same amount of insulin which had been newly exposed to fresh cells. Mid pretreatment of isolated hepatocytes with trypsin or chymotrypsin at concentrations of 5 to 20 mug/ml depressed to the same degree the amount of 125-I-insulin bound at steady state and the 125I-insulin degradation velocity. Peptide or protein hormones unrelated to insulin, including the oxidized A and B chains of insulin, failed to depress the amount of insulin bound or the velocity of insulin degradation when present at concentrations of 10-5 or 10-6 M. Over a wide range of concentrations, various synthetic insulin analogues and naturally occurring insulins depressed to the same degree the amount of 125I-insulin bound at steady state and the 125I-insulin degradation velocity. These observations suggest that insulin bound to hepatocyte plasma membranes is the substrate for insulin degradation by the liver.", "contents": "Binding and degradation of 125I-insulin by rat hepatocytes. The binding and the velocity of degradation of 125I-insulin in the absence or presence of varying concentrations of native procline insulin were studied using isolated rat hepatocytes. At insulin concentrations ranging from 5 X 10(-11) to 10(-6) M, insulin degradation velocity showed a first order dependence on the total concentration of insulin bound at steady state. The overall reaction had an apparent rate constant of 0.030 +/- 0.011 min-1. Furthermore, the degradation of a given amount of 125I-insulin bound to cells was more rapid and extensive than the degradation of the same amount of insulin which had been newly exposed to fresh cells. Mid pretreatment of isolated hepatocytes with trypsin or chymotrypsin at concentrations of 5 to 20 mug/ml depressed to the same degree the amount of 125-I-insulin bound at steady state and the 125I-insulin degradation velocity. Peptide or protein hormones unrelated to insulin, including the oxidized A and B chains of insulin, failed to depress the amount of insulin bound or the velocity of insulin degradation when present at concentrations of 10-5 or 10-6 M. Over a wide range of concentrations, various synthetic insulin analogues and naturally occurring insulins depressed to the same degree the amount of 125I-insulin bound at steady state and the 125I-insulin degradation velocity. These observations suggest that insulin bound to hepatocyte plasma membranes is the substrate for insulin degradation by the liver."} {"id": "PMID:172498", "title": "Avian myeloblastosis virus DNA polymerase. Kinetic studies on the incorporation of noncomplementary nucleotides.", "content": "The high error rate characteristic of DNA polymerases from RNA tumor viruses has permitted measurements on the simultaneous incorporation of complementary and noncomplementary nucleotides during DNA synthesis. For example, avian myeloblastosis virus DNA polymerase incorporates 1 molecule of dCMP for approximately 500 molecules of dTMP polymerized using polyriboadenylic acid as a template. The parallel incorporation of complementary and noncomplementary nucleotides afer gel filtration of avian myeloblastosis virus DNA polymerase indicates that the observed fidelity is catalyzed by the polymerase itself. Nearest neighbor analysis of the product indicates that noncomplementary nucleotides are incorporated as single base substitutions. The incorporation of the noncomplementary dCMP is not reduced by a 20-fold greater amount of the complementary nucleotide, dTTP. Conversely, the concentration of the noncomplementary nucleotides does not effect the rate of incorporation of the complementary nucleotide. A similar lack of competition between complementary dGTP and noncomplementary dATP is exhibited using poly(rC)-oligo(dG) as a template-primer. Furthermore, there was no detectable competition between the different noncomplementary nucleotides. Possible explanations for this lack of competition are considered.", "contents": "Avian myeloblastosis virus DNA polymerase. Kinetic studies on the incorporation of noncomplementary nucleotides. The high error rate characteristic of DNA polymerases from RNA tumor viruses has permitted measurements on the simultaneous incorporation of complementary and noncomplementary nucleotides during DNA synthesis. For example, avian myeloblastosis virus DNA polymerase incorporates 1 molecule of dCMP for approximately 500 molecules of dTMP polymerized using polyriboadenylic acid as a template. The parallel incorporation of complementary and noncomplementary nucleotides afer gel filtration of avian myeloblastosis virus DNA polymerase indicates that the observed fidelity is catalyzed by the polymerase itself. Nearest neighbor analysis of the product indicates that noncomplementary nucleotides are incorporated as single base substitutions. The incorporation of the noncomplementary dCMP is not reduced by a 20-fold greater amount of the complementary nucleotide, dTTP. Conversely, the concentration of the noncomplementary nucleotides does not effect the rate of incorporation of the complementary nucleotide. A similar lack of competition between complementary dGTP and noncomplementary dATP is exhibited using poly(rC)-oligo(dG) as a template-primer. Furthermore, there was no detectable competition between the different noncomplementary nucleotides. Possible explanations for this lack of competition are considered."} {"id": "PMID:172499", "title": "Amino acid sequence of cytochrome c' from the purple photosynthetic bacterium Rhodospirillum rubrum S1.", "content": "The amino acid sequence of cytochrome c' from the purple photosynthetic bacterium Rhodospirillum rubrum S1 has been determined and is consistent with homology to cytochrome c' from the nonphotosynthetic bacterium Alcaligenes sp. NCIB 11015. There is 29% identity in the chosen alignment of these two proteins. R. rubrum cytochrome c' is composed of a single peptide chain of 126 amino acid residues with a single heme covalently bound near the COOH terminus. There is no sequence similarity to mitochondrial cytochrome c, except at the heme binding site.", "contents": "Amino acid sequence of cytochrome c' from the purple photosynthetic bacterium Rhodospirillum rubrum S1. The amino acid sequence of cytochrome c' from the purple photosynthetic bacterium Rhodospirillum rubrum S1 has been determined and is consistent with homology to cytochrome c' from the nonphotosynthetic bacterium Alcaligenes sp. NCIB 11015. There is 29% identity in the chosen alignment of these two proteins. R. rubrum cytochrome c' is composed of a single peptide chain of 126 amino acid residues with a single heme covalently bound near the COOH terminus. There is no sequence similarity to mitochondrial cytochrome c, except at the heme binding site."} {"id": "PMID:172500", "title": "Effect of serum on phenylalanine hydroxylase levels in cultured hepatoma cells.", "content": "Continued high levels of phenylalanine hydroxylase in cultured H4-II-E-C3 rat hepatoma cells require either serum or glucocorticoids in the culture medium. Upon withdrawal of serum, cellular phenylalanine hydroxylase levels decay exponentially with a half-life of 22 hours for about 60 hours, after which time a low, constant enzyme content persists for at least 96 hours. This decline of phenylalanine hydroxylase is fully reversible; normal enzyme levels are restored in a time- and dosage-dependent fashion upon addition of serum to basal cultures. The serum factor is nondialyzable and moderately heat-stable. The stimulation by serum of the phenylalanine hydroxylas content of basal cultures is blocked by 3-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]glutarimide and requires ongoing cellular protein synthesis. When added to the enzyme-assay mixture in vitro, serum does not alter the phenylalanine hydroxylase activity of extracts from basal cultures. Three lines of evidence suggest that serum contains a nonsteroidal phenylalanine hydroxylase stimulatory components(s): (a) glucocorticoid antagonists inhibit less than one-half of the biological activity of serum; (b) exhaustive extraction of endogenous serum glucocorticoids with charcoal reduces the activity of serum to about one-half of control values; and (c) the stimulatory effects of charcoal reduces the values; and (c) the stimulatory effects of charcoal-extracted serum and hydrocortisone are additive. The phenylalanine hydroxylase stimulatory activities of the charcoal-extracted sera from four mammalian species and from three stages in development in one mammalian species are comparable. A survey of partially purified preparations of a number of known hormones failed to reveal any one capable of elevating the phenylalanine hydroxylas levels of basal cultures in a manner comparable to that of charcoal-extracted serum.", "contents": "Effect of serum on phenylalanine hydroxylase levels in cultured hepatoma cells. Continued high levels of phenylalanine hydroxylase in cultured H4-II-E-C3 rat hepatoma cells require either serum or glucocorticoids in the culture medium. Upon withdrawal of serum, cellular phenylalanine hydroxylase levels decay exponentially with a half-life of 22 hours for about 60 hours, after which time a low, constant enzyme content persists for at least 96 hours. This decline of phenylalanine hydroxylase is fully reversible; normal enzyme levels are restored in a time- and dosage-dependent fashion upon addition of serum to basal cultures. The serum factor is nondialyzable and moderately heat-stable. The stimulation by serum of the phenylalanine hydroxylas content of basal cultures is blocked by 3-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]glutarimide and requires ongoing cellular protein synthesis. When added to the enzyme-assay mixture in vitro, serum does not alter the phenylalanine hydroxylase activity of extracts from basal cultures. Three lines of evidence suggest that serum contains a nonsteroidal phenylalanine hydroxylase stimulatory components(s): (a) glucocorticoid antagonists inhibit less than one-half of the biological activity of serum; (b) exhaustive extraction of endogenous serum glucocorticoids with charcoal reduces the activity of serum to about one-half of control values; and (c) the stimulatory effects of charcoal reduces the values; and (c) the stimulatory effects of charcoal-extracted serum and hydrocortisone are additive. The phenylalanine hydroxylase stimulatory activities of the charcoal-extracted sera from four mammalian species and from three stages in development in one mammalian species are comparable. A survey of partially purified preparations of a number of known hormones failed to reveal any one capable of elevating the phenylalanine hydroxylas levels of basal cultures in a manner comparable to that of charcoal-extracted serum."} {"id": "PMID:172501", "title": "Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease.", "content": "The hydrolysis of cholesteryl esters contained in plasma low density lipoprotein was reduced in cultured fibroblasts derived from a patient with cholesteryl ester storage disease, an inborn error of metabolism in which lysosomal acid lipase activity is deficient. While these mutant cells showed a normal ability to bind low density lipoprotein at its high affinity cell surface receptor site, to take up the bound lipoprotein through endocytosis, and to hydrolyze the protein component of the lipoprotein in lysosomes, their defective lysosomal hydrolysis of the cholesteryl ester component of the lipoprotein led to the accumulation within the cell of unhydrolyzed cholesteryl esters, the fatty acid distribution of which resembled that of plasma lipoprotein. When the cholesteryl ester storage disease cells were incubated with low density lipoprotein, the reduced rate of liberation of free cholesterol by these mutant cells was associated with a delay in the occurrence of two lipoprotein-mediated regulatory events, suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and activation of endogenous cholesteryl ester formation. In contrast to their defective hydrolysis of exogenously derived lipoprotein-bound cholesteryl esters, the choleseryl ester storage disease cells showed a normal rate of hydrolysis of cholesteryl esters that had been synthesized within the cell. These data lend support to the concept that in cultured human fibroblasts cholesteryl esters entering the cell bound to low density lipoprotein are hydrolyzed within the lysosome and that one of the functions of this intracellular organelle is to supply the cell with free cholesterol.", "contents": "Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease. The hydrolysis of cholesteryl esters contained in plasma low density lipoprotein was reduced in cultured fibroblasts derived from a patient with cholesteryl ester storage disease, an inborn error of metabolism in which lysosomal acid lipase activity is deficient. While these mutant cells showed a normal ability to bind low density lipoprotein at its high affinity cell surface receptor site, to take up the bound lipoprotein through endocytosis, and to hydrolyze the protein component of the lipoprotein in lysosomes, their defective lysosomal hydrolysis of the cholesteryl ester component of the lipoprotein led to the accumulation within the cell of unhydrolyzed cholesteryl esters, the fatty acid distribution of which resembled that of plasma lipoprotein. When the cholesteryl ester storage disease cells were incubated with low density lipoprotein, the reduced rate of liberation of free cholesterol by these mutant cells was associated with a delay in the occurrence of two lipoprotein-mediated regulatory events, suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and activation of endogenous cholesteryl ester formation. In contrast to their defective hydrolysis of exogenously derived lipoprotein-bound cholesteryl esters, the choleseryl ester storage disease cells showed a normal rate of hydrolysis of cholesteryl esters that had been synthesized within the cell. These data lend support to the concept that in cultured human fibroblasts cholesteryl esters entering the cell bound to low density lipoprotein are hydrolyzed within the lysosome and that one of the functions of this intracellular organelle is to supply the cell with free cholesterol."} {"id": "PMID:172502", "title": "Saccharopine dehydrogenase. Substrate inhibition studies.", "content": "In the direction of reductive condensation of alpha-ketoglutarate and lysine, saccharopine dehydrogenase (N6-(glutar-2-yl)-L-lysine:NAD oxidoreductase (lysine-forming) is inhibited by high concentrations of alpha-ketoglutarate and lysine, but not by NADH. NAD+ and saccharopine show no substrate inhibition in the reverse direction. Substrate inhibition by alpha-ketoglutarate and lysine is linear uncompetitive versus NADH. However, when the inhibition is examined with alpha-ketoglutarate or lysine as the variable substrate, the double reciprocal plots show a family of curved lines concave up. The curvature is more pronounced with increasing concentrations of the inhibitory substrate, suggesting an interaction of variable substrate with the enzyme form carrying the inhibitory substrate. These inhibition patterns, the lack of interaction of structural analogs of lysine such as ornithine and norleucine with the E-NAD+ complex (Fujioka M., and Nakatani, Y. (1972) Eur. J. Biochem. 25, 301-307), the identity of values of inhibition constants of alpha-ketoglutarate and lysine obtained with either one as the substrate inhibitor, and the substrate inhibition data in the presence of a reaction product, NAD+, are consistent with the mechanism that substrate inhibition results from the formation of a dead-end E-NAD+-alpha-ketoglutarate complex followed by the addition of lysine to this abortive complex.", "contents": "Saccharopine dehydrogenase. Substrate inhibition studies. In the direction of reductive condensation of alpha-ketoglutarate and lysine, saccharopine dehydrogenase (N6-(glutar-2-yl)-L-lysine:NAD oxidoreductase (lysine-forming) is inhibited by high concentrations of alpha-ketoglutarate and lysine, but not by NADH. NAD+ and saccharopine show no substrate inhibition in the reverse direction. Substrate inhibition by alpha-ketoglutarate and lysine is linear uncompetitive versus NADH. However, when the inhibition is examined with alpha-ketoglutarate or lysine as the variable substrate, the double reciprocal plots show a family of curved lines concave up. The curvature is more pronounced with increasing concentrations of the inhibitory substrate, suggesting an interaction of variable substrate with the enzyme form carrying the inhibitory substrate. These inhibition patterns, the lack of interaction of structural analogs of lysine such as ornithine and norleucine with the E-NAD+ complex (Fujioka M., and Nakatani, Y. (1972) Eur. J. Biochem. 25, 301-307), the identity of values of inhibition constants of alpha-ketoglutarate and lysine obtained with either one as the substrate inhibitor, and the substrate inhibition data in the presence of a reaction product, NAD+, are consistent with the mechanism that substrate inhibition results from the formation of a dead-end E-NAD+-alpha-ketoglutarate complex followed by the addition of lysine to this abortive complex."} {"id": "PMID:172503", "title": "Adenosine 3':5'-monophosphate-regulated phosphorylation of erythrocyte membrane proteins. Separation of membrane-associated cyclic adenosine 3':5'-monophosphate-dependent protein kinase from its endogenous substrates.", "content": "An adenosine 3':5'-monophosphate (cyclic AMP)-binding protein in the human erythrocyte plasma membrane was isotopically labeled using a photoaffinity analog of cyclic AMP, N6-(ethyl 2-diazomalonyl) cyclic [3H]AMP. The cyclic AMP-binding site is located in a polypeptide chain having a molecular weight of 48,000. Cyclic AMP-binding protein and cyclic AMP-dependent protein kinase were solubilized with 0.5% Triton X-100 in 56 mM sodium borate, pH 8, but 32P-labeled membrane phosphoproteins were retained in the Triton-insoluble fraction, suggesting that the membrane-associated binding protein is not a primary substrate for protein kinase. Triton-solubilized and membrane-associated protein kinase activities were stimulated 15- and 17-fold by cyclic AMP, suggesting that the degree of association between the catalytic anc cyclic AMP-binding components was very similar in both preparations. Fractionation and characterization of membrane phosphoproteins have shown that protein III and a co-migrating minor protein are substrates for protein kinase but membrane sialoglycoproteins are not phosphorylated.", "contents": "Adenosine 3':5'-monophosphate-regulated phosphorylation of erythrocyte membrane proteins. Separation of membrane-associated cyclic adenosine 3':5'-monophosphate-dependent protein kinase from its endogenous substrates. An adenosine 3':5'-monophosphate (cyclic AMP)-binding protein in the human erythrocyte plasma membrane was isotopically labeled using a photoaffinity analog of cyclic AMP, N6-(ethyl 2-diazomalonyl) cyclic [3H]AMP. The cyclic AMP-binding site is located in a polypeptide chain having a molecular weight of 48,000. Cyclic AMP-binding protein and cyclic AMP-dependent protein kinase were solubilized with 0.5% Triton X-100 in 56 mM sodium borate, pH 8, but 32P-labeled membrane phosphoproteins were retained in the Triton-insoluble fraction, suggesting that the membrane-associated binding protein is not a primary substrate for protein kinase. Triton-solubilized and membrane-associated protein kinase activities were stimulated 15- and 17-fold by cyclic AMP, suggesting that the degree of association between the catalytic anc cyclic AMP-binding components was very similar in both preparations. Fractionation and characterization of membrane phosphoproteins have shown that protein III and a co-migrating minor protein are substrates for protein kinase but membrane sialoglycoproteins are not phosphorylated."} {"id": "PMID:172504", "title": "Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action.", "content": "The role of the carbohydrate part of human chorionic gonadotropin (hCG) was investigated by measuring the ability of hCG derivatives lacking various sugar residues to bind to rat Leydig cells and stimulate them to synthesize testosterone and cyclic adenosine 3':5'-monophosphate (cyclic AMP). Whereas sequential removal of the sialic acid, galactose, N-acetylglucosamine, and mannose residues led to a progressive increase in the effective dose of the hormone required to stimulate steroidogenesis, it resulted in a marked loss in the ability of the hormone to stimulate cyclic AMP accumulation. Low doses of the glycosidase-treated hormone derivatives were additive with hCG when their ability to stimulate testosterone synthesis was analyzed. Nevertheless, the glycosidase-treated derivatives were potent inhibitors of hCG-induced cyclic AMP accumulation, suggesting that removal of the sugars did not influence binding of the hormone to the cell as much as it reduced the ability of the bound hormone to activate adenyl cyclase. This hypothesis was further supported by our finding that the hCG derivatives were highly effective inhibitors of 125I-hGC binding to the intact cells. Removal of sialic acid and galactose enhanced the inhibition, whereas removal of all the sugar residues only decreased the inhibition slightly. The degree of these effects was comparatively small. The possibility that steroidogenesis and cyclic AMP accumulation are altered independently by hCG stimulation is discussed.", "contents": "Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action. The role of the carbohydrate part of human chorionic gonadotropin (hCG) was investigated by measuring the ability of hCG derivatives lacking various sugar residues to bind to rat Leydig cells and stimulate them to synthesize testosterone and cyclic adenosine 3':5'-monophosphate (cyclic AMP). Whereas sequential removal of the sialic acid, galactose, N-acetylglucosamine, and mannose residues led to a progressive increase in the effective dose of the hormone required to stimulate steroidogenesis, it resulted in a marked loss in the ability of the hormone to stimulate cyclic AMP accumulation. Low doses of the glycosidase-treated hormone derivatives were additive with hCG when their ability to stimulate testosterone synthesis was analyzed. Nevertheless, the glycosidase-treated derivatives were potent inhibitors of hCG-induced cyclic AMP accumulation, suggesting that removal of the sugars did not influence binding of the hormone to the cell as much as it reduced the ability of the bound hormone to activate adenyl cyclase. This hypothesis was further supported by our finding that the hCG derivatives were highly effective inhibitors of 125I-hGC binding to the intact cells. Removal of sialic acid and galactose enhanced the inhibition, whereas removal of all the sugar residues only decreased the inhibition slightly. The degree of these effects was comparatively small. The possibility that steroidogenesis and cyclic AMP accumulation are altered independently by hCG stimulation is discussed."} {"id": "PMID:172505", "title": "Functional intermediates in the reaction of membrane-bound cytochrome oxidase with oxygen.", "content": "Flash photolysis of the membrane-bound cytochrome oxidase/carbon monoxide compound in the presence of oxygen at low temperatures and in the frozen state leads to the formation of three types of intermediates functional in electron transfer in cytochrome oxidase and reduction of oxygen by cytochrome oxidase. The first category (A) does not involve electron transfer to oxygen between -125 degrees and -105 degrees, and includes oxy compounds which are spectroscopically similar for the completely reduced oxidase (Cu1+alpha3(2+)-O2) or for the ferricyanide-pretreated oxidase (Cu2+alpha3(3+)-O2). Oxygen is readily dissociated from compounds of type A. The second category (B) involves oxidation of the heme and the copper moiety of the reduced oxidase to form a peroxy compound (Cu2+alpha 3(3+)-O2=or Cu2+alpha3(2+)-O2H2) in the temperature range from -105 degrees to -60 degrees. Above -60 degrees, compounds of type B serve as effective electron acceptors from cytochromes a, c, and c1. The third category (C) is formed above -100 degrees from mixed valency states of the oxidase obtained by ferricyanide pretreatment, and may involve higher valency states of the heme iron (Cu2+alpha3(4+)-O2=). These compounds act as electron acceptors for the respiratory chain and as functional intermediates in oxygen reduction. The remarkable features of cytochrome oxidase are its highly dissociable \"oxy\" compound and its extremely effective electron donor reaction which converts this rapidly to tightly bound reduced oxygen and oxidized oxidase.", "contents": "Functional intermediates in the reaction of membrane-bound cytochrome oxidase with oxygen. Flash photolysis of the membrane-bound cytochrome oxidase/carbon monoxide compound in the presence of oxygen at low temperatures and in the frozen state leads to the formation of three types of intermediates functional in electron transfer in cytochrome oxidase and reduction of oxygen by cytochrome oxidase. The first category (A) does not involve electron transfer to oxygen between -125 degrees and -105 degrees, and includes oxy compounds which are spectroscopically similar for the completely reduced oxidase (Cu1+alpha3(2+)-O2) or for the ferricyanide-pretreated oxidase (Cu2+alpha3(3+)-O2). Oxygen is readily dissociated from compounds of type A. The second category (B) involves oxidation of the heme and the copper moiety of the reduced oxidase to form a peroxy compound (Cu2+alpha 3(3+)-O2=or Cu2+alpha3(2+)-O2H2) in the temperature range from -105 degrees to -60 degrees. Above -60 degrees, compounds of type B serve as effective electron acceptors from cytochromes a, c, and c1. The third category (C) is formed above -100 degrees from mixed valency states of the oxidase obtained by ferricyanide pretreatment, and may involve higher valency states of the heme iron (Cu2+alpha3(4+)-O2=). These compounds act as electron acceptors for the respiratory chain and as functional intermediates in oxygen reduction. The remarkable features of cytochrome oxidase are its highly dissociable \"oxy\" compound and its extremely effective electron donor reaction which converts this rapidly to tightly bound reduced oxygen and oxidized oxidase."} {"id": "PMID:172507", "title": "Glycoproteins released into the culture medium of differentiating murine neuroblastoma cells.", "content": "C-1300 murine neuroblastoma cells release glycoproteins into the culture medium. The process was studied by prelabeling spinner cultures for 12 to 60 hours with [3H]glucosamine. Then, the medium was removed and replaced with fresh medium lacking radioactive isotope. Soluble material released into the medium during the subsequent 2-hour incubation was collected by trichloroacetic acid precipitation. The released proteins were then separated by discontinuous polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. The electrophoretograms of glycoproteins obtained from cultures labeled for different lengths of time were very similar; three major radioactive regions centered about molecular weights 87,000, 66,000, and 55,000 were present. When spinner cells were transferred to monolayer culture in the presence of N6,O2' dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP), differentiation (extension of neurites twice the diameter of the perikaryon) was observed. Monolayer cultures grown in the presence of Bt2cAMP and [3H]glucosamine for 12 hours released glycoproteins which gave a gel electrophoresis pattern similar to that obtained using spinner cultures. However, after 60 hours in the presence of Bt2cAMP and [3H]glucosamine, the released radioactive material consisted almost exclusively of glycoproteins of the 66,000 molecular weight class. Similar results were obtained if [3H]fucose was substituted for [3H]glucosamine, or if bromodeoxyuridine (which also induced differentiation) was substituted for Bt2cAMP. Similar experiments using radioactive amino acids were conducted with both spinner and monolayer cultures. Much of the released radioactive material was contained in the same three molecular weight classes as the glycoproteins released by spinner cells prelabeled with [3H]glucosamine, and this pattern did not vary with length of labeling period or type of culture. These results may imply that the glycosylation of released proteins is influenced by agents which can induce differentiation. The origin of this released material is discussed. [3H]Glucosamine-labeled glycoproteins of the molecular weight class centered about 55,000 (discussed above) were isolated by preparative gel electrophoresis. They co-migrated with authentic mouse brain microtubular protein as two closely spaced bands on a number of different electrophoretic systems. This protein fraction was also characterized as complexing with a monospecific antitubulin antibody.", "contents": "Glycoproteins released into the culture medium of differentiating murine neuroblastoma cells. C-1300 murine neuroblastoma cells release glycoproteins into the culture medium. The process was studied by prelabeling spinner cultures for 12 to 60 hours with [3H]glucosamine. Then, the medium was removed and replaced with fresh medium lacking radioactive isotope. Soluble material released into the medium during the subsequent 2-hour incubation was collected by trichloroacetic acid precipitation. The released proteins were then separated by discontinuous polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. The electrophoretograms of glycoproteins obtained from cultures labeled for different lengths of time were very similar; three major radioactive regions centered about molecular weights 87,000, 66,000, and 55,000 were present. When spinner cells were transferred to monolayer culture in the presence of N6,O2' dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP), differentiation (extension of neurites twice the diameter of the perikaryon) was observed. Monolayer cultures grown in the presence of Bt2cAMP and [3H]glucosamine for 12 hours released glycoproteins which gave a gel electrophoresis pattern similar to that obtained using spinner cultures. However, after 60 hours in the presence of Bt2cAMP and [3H]glucosamine, the released radioactive material consisted almost exclusively of glycoproteins of the 66,000 molecular weight class. Similar results were obtained if [3H]fucose was substituted for [3H]glucosamine, or if bromodeoxyuridine (which also induced differentiation) was substituted for Bt2cAMP. Similar experiments using radioactive amino acids were conducted with both spinner and monolayer cultures. Much of the released radioactive material was contained in the same three molecular weight classes as the glycoproteins released by spinner cells prelabeled with [3H]glucosamine, and this pattern did not vary with length of labeling period or type of culture. These results may imply that the glycosylation of released proteins is influenced by agents which can induce differentiation. The origin of this released material is discussed. [3H]Glucosamine-labeled glycoproteins of the molecular weight class centered about 55,000 (discussed above) were isolated by preparative gel electrophoresis. They co-migrated with authentic mouse brain microtubular protein as two closely spaced bands on a number of different electrophoretic systems. This protein fraction was also characterized as complexing with a monospecific antitubulin antibody."} {"id": "PMID:172508", "title": "High molecular weight RNAs from Rous sarcoma virus and Moloney murine leukemia virus contain two subunits.", "content": "The molecular weights of the large genomic RNAs from Rous sarcoma and Moloney murine leukemia viruses were determined by a combination of sedimentation coefficients and retardation coefficients from gel electrophoresis. Six RNA standards, ranging from 0.7 X 10(6) to 5.3 X 10(6) daltons, were employed. Studies in the presence of varying concentrations of Mg2+ showed that the method provided valid molecular weights for RNAs of differing amounts of ordered structure. The molecular weight (X 10(-6)) of the high molecular weight RNA complexe from Rous sarcoma virus was 7.6 (+/-0.3) and from murine leukemia virus was 6.9 (+/-0.3). The molecular weights (X 10 (-6) of their Subunits were 3.3 (+/-0.1) and 2.8 (+/-0.2), respectively. Hence, the large complexes consisted of two, not three or more, subunits plus small associated RNAs. The high molecular weight RNA from cloned Rous sarcoma virus was heterogenous in molecular weight although the apparent molecular radius was constant; stuides were performed on subfractions of the RNA as well as on RNA from virus harvested at various time intervals. The preparations with lowest molecular weight approached a mass equal to twice that of the subunit, with hydrodynamic properties approaching those expected of normal single-stranded RNA.", "contents": "High molecular weight RNAs from Rous sarcoma virus and Moloney murine leukemia virus contain two subunits. The molecular weights of the large genomic RNAs from Rous sarcoma and Moloney murine leukemia viruses were determined by a combination of sedimentation coefficients and retardation coefficients from gel electrophoresis. Six RNA standards, ranging from 0.7 X 10(6) to 5.3 X 10(6) daltons, were employed. Studies in the presence of varying concentrations of Mg2+ showed that the method provided valid molecular weights for RNAs of differing amounts of ordered structure. The molecular weight (X 10(-6)) of the high molecular weight RNA complexe from Rous sarcoma virus was 7.6 (+/-0.3) and from murine leukemia virus was 6.9 (+/-0.3). The molecular weights (X 10 (-6) of their Subunits were 3.3 (+/-0.1) and 2.8 (+/-0.2), respectively. Hence, the large complexes consisted of two, not three or more, subunits plus small associated RNAs. The high molecular weight RNA from cloned Rous sarcoma virus was heterogenous in molecular weight although the apparent molecular radius was constant; stuides were performed on subfractions of the RNA as well as on RNA from virus harvested at various time intervals. The preparations with lowest molecular weight approached a mass equal to twice that of the subunit, with hydrodynamic properties approaching those expected of normal single-stranded RNA."} {"id": "PMID:172509", "title": "All intact subunit RNAs from Rous sarcoma virus contain poly (A).", "content": "The capacity of RNA subunits of Schmidt-Ruppin Rous sarcoma virus to bind (dT)n was studied by cesium sulfate density gradient centrifugation, sucrose gradient centrifugation, or polyacrylamide gel electrophoresis. Two classes of subunits were observed. In agreement with previous reports, 60 to 70% of the purified subunits were capable of binding (dT)n. The remaining, nonbinding RNAs, although indistinguishable in size from whole subunits, were shown to be fragments that had lost the (rA)n terminus by random nucleolytic cleavage. This was deduced from the molecular weight distribution of the nonbinding RNAs from high molecular weight RNA. In addition, virtually all subunit RNA from early harvest virus, which contains a greater proportion of intact subunit, binds (dT)n.", "contents": "All intact subunit RNAs from Rous sarcoma virus contain poly (A). The capacity of RNA subunits of Schmidt-Ruppin Rous sarcoma virus to bind (dT)n was studied by cesium sulfate density gradient centrifugation, sucrose gradient centrifugation, or polyacrylamide gel electrophoresis. Two classes of subunits were observed. In agreement with previous reports, 60 to 70% of the purified subunits were capable of binding (dT)n. The remaining, nonbinding RNAs, although indistinguishable in size from whole subunits, were shown to be fragments that had lost the (rA)n terminus by random nucleolytic cleavage. This was deduced from the molecular weight distribution of the nonbinding RNAs from high molecular weight RNA. In addition, virtually all subunit RNA from early harvest virus, which contains a greater proportion of intact subunit, binds (dT)n."} {"id": "PMID:172510", "title": "Membrane-associated thiamin triphosphatase. II. Activation by divalent cations.", "content": "Activation of membrane-associated thiamin triphosphatase from rat brain requires a divalent cation (Mg2+, Ca2+, or Mn2+). The optimum concentration of Mg2+ necessary for maximal enzyme activity varies with substrate concentration; conversely, the maximal rate of hydrolysis attainbale by increasing thiamin triphosphate concentration is directly proportional to [Mg2+] for all levels of Mg2+ below that of the substrate. Under appropriate conditions, the Km of the thiamin triphosphatase for Mg2+ and for thiamin triphosphate are shown to be identical. Dissociation constants (Kd) for the binding of Mg2+ to thiamin triphosphate, thiamin diphosphate, and thiamin were determined; kinetic data re-expressed in terms of [Mg2+-thiamin triphosphate] conform to simple single substrate predictions, suggesting that the true enzyme substrate may be the Mg2+-thiamin triphosphate complex. Excess free Mg2+ inhibits thiamin triphosphatase activity competitively while excess free thiamin triphosphate in concentrations up to 10 times Km has no effect on the membrane-bound enzyme.", "contents": "Membrane-associated thiamin triphosphatase. II. Activation by divalent cations. Activation of membrane-associated thiamin triphosphatase from rat brain requires a divalent cation (Mg2+, Ca2+, or Mn2+). The optimum concentration of Mg2+ necessary for maximal enzyme activity varies with substrate concentration; conversely, the maximal rate of hydrolysis attainbale by increasing thiamin triphosphate concentration is directly proportional to [Mg2+] for all levels of Mg2+ below that of the substrate. Under appropriate conditions, the Km of the thiamin triphosphatase for Mg2+ and for thiamin triphosphate are shown to be identical. Dissociation constants (Kd) for the binding of Mg2+ to thiamin triphosphate, thiamin diphosphate, and thiamin were determined; kinetic data re-expressed in terms of [Mg2+-thiamin triphosphate] conform to simple single substrate predictions, suggesting that the true enzyme substrate may be the Mg2+-thiamin triphosphate complex. Excess free Mg2+ inhibits thiamin triphosphatase activity competitively while excess free thiamin triphosphate in concentrations up to 10 times Km has no effect on the membrane-bound enzyme."} {"id": "PMID:172511", "title": "Reconstitution of Bacillus stearothermophilus 50 S ribosomal subunits from purified molecular components.", "content": "Bacillus stearothermophilus 50 S ribosomal subunits have been reconstituted from a mixture of purified RNA and protein components. The protein fraction of 50 S subunits was separated into 27 components by a combination of various methods including ion exchange and gel filtration chromatography. The individual proteins showed single bands in a variety of polyacrylamide gel electrophoresis systems, and nearly all showed single spots on two-dimensional polyacrylamide gels. The molecular weights of the proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An equimolar mixture of the purified proteins was combined with 23 S RNA and 5 S RNA to reconstitute active 50 S subunits by the procedure of Nomura and Erdmann (Nomura, M., and Erdmann, V. A. (1970) Nature 226, 1214-1218). Reconstituted 52 S subunits containing purified proteins were slightly more active than subunits reconstituted with an unfractionated total protein extract in poly(U)-dependent polyphenylalanine synthesis and showed comparable activity in various assays for ribosomal function. The reconstitution proceeded more rapidly with the mixture of purified proteins than with the total protein extract. Reconstituted 50 S subunits containing purified proteins co-sedimented with native 50 S subunits on sucrose gradients and had a similar protein compsoition. Initial experiments on the roles of the individual proteins in ribosomal structure and function were performed. B. stearothermophilus protein 13 was extracted from 50 S subunits under the same conditions as escherichia coli L7/L12, and the extraction had a similar effect on ribosomal function. When single proteins were omitted from reconstitution mixtures, in most cases the reconstituted 50 S subunits showed decreased activity in polypheylalanine synthesis.", "contents": "Reconstitution of Bacillus stearothermophilus 50 S ribosomal subunits from purified molecular components. Bacillus stearothermophilus 50 S ribosomal subunits have been reconstituted from a mixture of purified RNA and protein components. The protein fraction of 50 S subunits was separated into 27 components by a combination of various methods including ion exchange and gel filtration chromatography. The individual proteins showed single bands in a variety of polyacrylamide gel electrophoresis systems, and nearly all showed single spots on two-dimensional polyacrylamide gels. The molecular weights of the proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An equimolar mixture of the purified proteins was combined with 23 S RNA and 5 S RNA to reconstitute active 50 S subunits by the procedure of Nomura and Erdmann (Nomura, M., and Erdmann, V. A. (1970) Nature 226, 1214-1218). Reconstituted 52 S subunits containing purified proteins were slightly more active than subunits reconstituted with an unfractionated total protein extract in poly(U)-dependent polyphenylalanine synthesis and showed comparable activity in various assays for ribosomal function. The reconstitution proceeded more rapidly with the mixture of purified proteins than with the total protein extract. Reconstituted 50 S subunits containing purified proteins co-sedimented with native 50 S subunits on sucrose gradients and had a similar protein compsoition. Initial experiments on the roles of the individual proteins in ribosomal structure and function were performed. B. stearothermophilus protein 13 was extracted from 50 S subunits under the same conditions as escherichia coli L7/L12, and the extraction had a similar effect on ribosomal function. When single proteins were omitted from reconstitution mixtures, in most cases the reconstituted 50 S subunits showed decreased activity in polypheylalanine synthesis."} {"id": "PMID:172512", "title": "Conformational changes required for pyruvate kinase activity as modulated by monovalent cations.", "content": "The interaction of a series of alkylamines with muscle pyruvate kinase was investigated by kinetic and physical studies in order to understand the mechanisms by which certain monovalent cations can activate the enzyme and to define several of the important conformational changes necessary for catalytic activity. Monomethylammonium ion interacts with pyruvate kinase to activate the enzyme. Dimethyland trimethylammonium ions do not activate, but are competitive inhibitors against activating cations. Tetramethylammonium ion neither activates nor inhibits pyruvate kinase activity. When the enzyme is in the presence of monomethylammonium ion or dimethylammonium ion, a conformational change is observed by ultraviolet difference spectroscopy. This conformational change is similar to that observed with other activating cations and appears to be a necessary but no sufficient conformational change in the formation of an active complex. The interaction of the substrate phosphoenolpyruvate with the pyruvate kinase-Mn2+ complex in the presence of these cations was studied by water proton relaxation rate measurements. The affinity of the enzyme-Mn2+ complex for phosphoenolpyruvate is decreased by a factor of 5 in the presence of any of the alkylamines compared to the affinity measured in the presence of K+ or NH4+. No change in the Km of phosphoenolpyruvate is observed however when it is measured in the presence of monomethylammonium ion, suggesting that the decrease in affinity for the substrate is not the reason for lack of enzymic activity. The conformation of the ternary enzyme-Mn2+-phosphoenolpyruvate complex about the bound Mn2+, as reflected by the enhancement values (epsilont) measured, differs depending upon the nature of the monovalent cation. The epsilon t values measured in the presence of the alkylamines are larger (epsilont - 5.7 +/- 0.2) than those measured in the presence of K+ or NH4+ (epsilont = 1.9 +/- 0.1).", "contents": "Conformational changes required for pyruvate kinase activity as modulated by monovalent cations. The interaction of a series of alkylamines with muscle pyruvate kinase was investigated by kinetic and physical studies in order to understand the mechanisms by which certain monovalent cations can activate the enzyme and to define several of the important conformational changes necessary for catalytic activity. Monomethylammonium ion interacts with pyruvate kinase to activate the enzyme. Dimethyland trimethylammonium ions do not activate, but are competitive inhibitors against activating cations. Tetramethylammonium ion neither activates nor inhibits pyruvate kinase activity. When the enzyme is in the presence of monomethylammonium ion or dimethylammonium ion, a conformational change is observed by ultraviolet difference spectroscopy. This conformational change is similar to that observed with other activating cations and appears to be a necessary but no sufficient conformational change in the formation of an active complex. The interaction of the substrate phosphoenolpyruvate with the pyruvate kinase-Mn2+ complex in the presence of these cations was studied by water proton relaxation rate measurements. The affinity of the enzyme-Mn2+ complex for phosphoenolpyruvate is decreased by a factor of 5 in the presence of any of the alkylamines compared to the affinity measured in the presence of K+ or NH4+. No change in the Km of phosphoenolpyruvate is observed however when it is measured in the presence of monomethylammonium ion, suggesting that the decrease in affinity for the substrate is not the reason for lack of enzymic activity. The conformation of the ternary enzyme-Mn2+-phosphoenolpyruvate complex about the bound Mn2+, as reflected by the enhancement values (epsilont) measured, differs depending upon the nature of the monovalent cation. The epsilon t values measured in the presence of the alkylamines are larger (epsilont - 5.7 +/- 0.2) than those measured in the presence of K+ or NH4+ (epsilont = 1.9 +/- 0.1)."} {"id": "PMID:172514", "title": "Effects of serotonin, carbamylcholine, and ascorbic acid on leukocyte cyclic GMP and chemotaxis.", "content": "Serotonin, ascorbic acid, and carbamylcholine enhanced the chemotactic responsiveness of human monocytes to endotoxin-treated serum. These agents caused significant accumulation of cyclic GMP in monocytes. PMN leukocyte chemotaxis was also enhanced by these agents although significant increases in cyclic GMP were not demonstrated.", "contents": "Effects of serotonin, carbamylcholine, and ascorbic acid on leukocyte cyclic GMP and chemotaxis. Serotonin, ascorbic acid, and carbamylcholine enhanced the chemotactic responsiveness of human monocytes to endotoxin-treated serum. These agents caused significant accumulation of cyclic GMP in monocytes. PMN leukocyte chemotaxis was also enhanced by these agents although significant increases in cyclic GMP were not demonstrated."} {"id": "PMID:172516", "title": "A simple method for freeze-fracture of monolayer cultures.", "content": "A simple method is described for the freeze-fracture in situ of monolayer cultures grown on gold carriers coated with a thin layer of silicon monoxide. Preliminary observations on 3T3 mouse embryo fibroblasts indicate that this technique exposes large areas of cell membrane, making it possible to determine how areas of membrane specialization are related to the cell as a whole and to regions of cellular interaction. 3T3 cells cultured on silicon monoxide show no modification of growth properties compared to cells growing on Falcon plastic, and other cell lines also appear to grow well on this substrate.", "contents": "A simple method for freeze-fracture of monolayer cultures. A simple method is described for the freeze-fracture in situ of monolayer cultures grown on gold carriers coated with a thin layer of silicon monoxide. Preliminary observations on 3T3 mouse embryo fibroblasts indicate that this technique exposes large areas of cell membrane, making it possible to determine how areas of membrane specialization are related to the cell as a whole and to regions of cellular interaction. 3T3 cells cultured on silicon monoxide show no modification of growth properties compared to cells growing on Falcon plastic, and other cell lines also appear to grow well on this substrate."} {"id": "PMID:172515", "title": "Biogenesis of microsomal membrane glycoproteins in rat liver. I. Presence of glycoproteins in microsomes and cytosol.", "content": "The glycoproteins of microsomes and cytosol were studied. Various washing procedures did not release the proteins from the microsomes, and immunological tests demonstrated that the sialoproteins are not serum components. Low concentrations of deoxycholate and incubation in 0.25 M sucrose solution liberated a small amount of microsomal sialoprotein and this fraction exhibited a high degree of labeling of protein-bound N-acetylneuraminic acid. A part of the glycoprotein fraction could not be solubilized, even with a high concentration of the detergent. Thoroughly perfused rat liver contained sialoproteins in the particle-free supernate. The level of sialoprotein present could not be due to contamination with serum or broken organelles. The high in vivo incorporation of [3H]glucosamine into protein-bound sialic acid of Golgi membranes and cytosol was paralleled by a delayed and lesser rate of incorporation into the rough and smooth microsomal membranes. This incorporation pattern suggests the possibility that the glycoproteins of cytosol and Golgi may later be incorporated into the membrane of the endoplasmic reticulum.", "contents": "Biogenesis of microsomal membrane glycoproteins in rat liver. I. Presence of glycoproteins in microsomes and cytosol. The glycoproteins of microsomes and cytosol were studied. Various washing procedures did not release the proteins from the microsomes, and immunological tests demonstrated that the sialoproteins are not serum components. Low concentrations of deoxycholate and incubation in 0.25 M sucrose solution liberated a small amount of microsomal sialoprotein and this fraction exhibited a high degree of labeling of protein-bound N-acetylneuraminic acid. A part of the glycoprotein fraction could not be solubilized, even with a high concentration of the detergent. Thoroughly perfused rat liver contained sialoproteins in the particle-free supernate. The level of sialoprotein present could not be due to contamination with serum or broken organelles. The high in vivo incorporation of [3H]glucosamine into protein-bound sialic acid of Golgi membranes and cytosol was paralleled by a delayed and lesser rate of incorporation into the rough and smooth microsomal membranes. This incorporation pattern suggests the possibility that the glycoproteins of cytosol and Golgi may later be incorporated into the membrane of the endoplasmic reticulum."} {"id": "PMID:172518", "title": "Autoradiographic studies of nicotinic acid utilization in human-mouse heterokaryons and inhibition of utilization in newly-formed hybrid cells.", "content": "Although most mammalian cell lines can utilize either nicotinic acid or nicotinamide for the biosynthesis of nicotinamide adenine dinucleotide (NAD), thymidine kinase-deficient, mouse 3T3-4F cells are unable to utilize nicotinic acid. When 3T3-4E cells were fused with human D98/AH2 cells, autoradiography showed that the resultant heterokaryons synthesized NAD from nicotinic acid at rates comparable to the human parental cell. The rate of nicotinic acid utilization in heterokaryons remained unchanged over the four-day period of study following cell fusion. In contrast to the results observed with heterokaryons, nicotinic acid utilization was markedly reduced in hybrid cells. Of 100 hybrid clones examined at four or five days following cell fusion, 60 utilized nicotinic acid at rates less than one tenth that of the parental human cell. Similar results were observed in hybrid clones at nine or ten days following fusion. Uniformly high rates of NAD biosynthesis were observed in hybrid clones with nicotinamide as the precursor. This excludes the possibility that the reduction in nicotinic acid utilization in hybrid cells is due to a general metabolic dysfunction. The biochemical mechanism by which nicotinic acid utilization is markedly reduced has not been determined with certainty, however, several observations suggest genetic suppression.", "contents": "Autoradiographic studies of nicotinic acid utilization in human-mouse heterokaryons and inhibition of utilization in newly-formed hybrid cells. Although most mammalian cell lines can utilize either nicotinic acid or nicotinamide for the biosynthesis of nicotinamide adenine dinucleotide (NAD), thymidine kinase-deficient, mouse 3T3-4F cells are unable to utilize nicotinic acid. When 3T3-4E cells were fused with human D98/AH2 cells, autoradiography showed that the resultant heterokaryons synthesized NAD from nicotinic acid at rates comparable to the human parental cell. The rate of nicotinic acid utilization in heterokaryons remained unchanged over the four-day period of study following cell fusion. In contrast to the results observed with heterokaryons, nicotinic acid utilization was markedly reduced in hybrid cells. Of 100 hybrid clones examined at four or five days following cell fusion, 60 utilized nicotinic acid at rates less than one tenth that of the parental human cell. Similar results were observed in hybrid clones at nine or ten days following fusion. Uniformly high rates of NAD biosynthesis were observed in hybrid clones with nicotinamide as the precursor. This excludes the possibility that the reduction in nicotinic acid utilization in hybrid cells is due to a general metabolic dysfunction. The biochemical mechanism by which nicotinic acid utilization is markedly reduced has not been determined with certainty, however, several observations suggest genetic suppression."} {"id": "PMID:172519", "title": "The role of adenosine 3',5'-monophosphate in the transformation of Cloudman mouse melanoma cells.", "content": "The role of adenosine 3',5'-monophosphate (cyclic AMP) in the regulation of mouse melanoma cell growth and differentiation was investigated. A variant melanoma (Cloudman S91-F) which displays a greater degree of transformation than the parental cell (Cloudman S91) was isolated. A correlation between cyclic AMP metabolism and transformation was made. Dibutyryl cyclic AMP depressed cell growth and increased pigmentation in both parental and variant cell lines. The parental cell line, however, was more responsive to melanocyte-stimulating hormone (MSH) which was found to affect cell growth and pigmentation by increasing cyclic AMP levels. The more transformed S91-F cell line contained lower levels of cyclic AMP than the parental cell line, and this fact correlated well with the higher degree of growth and lesser degree of pigmentation in the variant. Enzymatic analysis revealed that the hydrolysis of cyclic AMP in both cell lines was similar, while the adenylate cyclase activity of the variant cell line was lower than that of the parental cell line. Lineweaver-Burk plots demonstrated that the Km's for the enzymes in the two cell lines were the same but that the Vmax of the S91-F cell line was significantly less that that of the S91 cell line. Thus, the lesion in the S91-F cell which is responsible for its more transformed characteristics seems to be one which affects adenylate cyclase at the level of the cell membrane.", "contents": "The role of adenosine 3',5'-monophosphate in the transformation of Cloudman mouse melanoma cells. The role of adenosine 3',5'-monophosphate (cyclic AMP) in the regulation of mouse melanoma cell growth and differentiation was investigated. A variant melanoma (Cloudman S91-F) which displays a greater degree of transformation than the parental cell (Cloudman S91) was isolated. A correlation between cyclic AMP metabolism and transformation was made. Dibutyryl cyclic AMP depressed cell growth and increased pigmentation in both parental and variant cell lines. The parental cell line, however, was more responsive to melanocyte-stimulating hormone (MSH) which was found to affect cell growth and pigmentation by increasing cyclic AMP levels. The more transformed S91-F cell line contained lower levels of cyclic AMP than the parental cell line, and this fact correlated well with the higher degree of growth and lesser degree of pigmentation in the variant. Enzymatic analysis revealed that the hydrolysis of cyclic AMP in both cell lines was similar, while the adenylate cyclase activity of the variant cell line was lower than that of the parental cell line. Lineweaver-Burk plots demonstrated that the Km's for the enzymes in the two cell lines were the same but that the Vmax of the S91-F cell line was significantly less that that of the S91 cell line. Thus, the lesion in the S91-F cell which is responsible for its more transformed characteristics seems to be one which affects adenylate cyclase at the level of the cell membrane."} {"id": "PMID:172520", "title": "Pyridine nucleotide metabolism in mitotic cells.", "content": "The biosynthesis and turnover of nicotinamide adenine dinucleotide (NAD) have been examined in mitotic cells of the human culture line, D98/AH2. No significant difference in the incorporation of nicotinic acid or nicotinamide could be detected between mitotic and interphase cells. The distribution of newly-incorporated nicotinic acid among the various pyridine nucleotides was also identical in mitotic and interphase cells. Whereas previous results have shown that the nucleus is necessary for NAD biosynthesis, the present results show that an intact nucleus is not required. In contrast to the equivalent rates of biosynthesis in mitotic and interphase cells, the pyridine ring of NAD was lost twice as fast from mitotic as from interphase cells. Loss of the pyridine ring to the medium is not necessarily an accurate measure of turnover, and the difference between mitotic and interphase cells may reflect differential reutilization of the pyridine ring within the cell. However, it is clear that NAD turnover is substantial in mitotic cells and possibly greater in mitotic cells than interphase cells.", "contents": "Pyridine nucleotide metabolism in mitotic cells. The biosynthesis and turnover of nicotinamide adenine dinucleotide (NAD) have been examined in mitotic cells of the human culture line, D98/AH2. No significant difference in the incorporation of nicotinic acid or nicotinamide could be detected between mitotic and interphase cells. The distribution of newly-incorporated nicotinic acid among the various pyridine nucleotides was also identical in mitotic and interphase cells. Whereas previous results have shown that the nucleus is necessary for NAD biosynthesis, the present results show that an intact nucleus is not required. In contrast to the equivalent rates of biosynthesis in mitotic and interphase cells, the pyridine ring of NAD was lost twice as fast from mitotic as from interphase cells. Loss of the pyridine ring to the medium is not necessarily an accurate measure of turnover, and the difference between mitotic and interphase cells may reflect differential reutilization of the pyridine ring within the cell. However, it is clear that NAD turnover is substantial in mitotic cells and possibly greater in mitotic cells than interphase cells."} {"id": "PMID:172521", "title": "Regulation of growth and morphological modulation of HeLa65 cells in monolayer culture by dibutyryl cyclic AMP, butyrate and their analogs.", "content": "N6-O2'-Dibutyryl adenosine-3',5' monophosphate (DBcAMP) markedly altered the morphology of HeLa cells by increasing average cell size with an increase in total cell protein and RNA. Such effects were not caused by adenosine 3',5' monophosphate (cAMP) or related nucleosides and nucleotides. Butyrate, an enzyme catalyzed hydrolysis product of DBcAMP, induced a jagged spindle shape in HeLa cells within 8 hours and then caused them to enlarge and resemble those grown with DBcAMP. These effects were specific for butyrate (C4) and pentanoate (C5) and were not observed with isomers, substituted analogs, or other fatty acid derivatives. These morphological effects were prevented by blocking protein synthesis or by altering the cytoskeleton with Colcemide or cytochalasin B.", "contents": "Regulation of growth and morphological modulation of HeLa65 cells in monolayer culture by dibutyryl cyclic AMP, butyrate and their analogs. N6-O2'-Dibutyryl adenosine-3',5' monophosphate (DBcAMP) markedly altered the morphology of HeLa cells by increasing average cell size with an increase in total cell protein and RNA. Such effects were not caused by adenosine 3',5' monophosphate (cAMP) or related nucleosides and nucleotides. Butyrate, an enzyme catalyzed hydrolysis product of DBcAMP, induced a jagged spindle shape in HeLa cells within 8 hours and then caused them to enlarge and resemble those grown with DBcAMP. These effects were specific for butyrate (C4) and pentanoate (C5) and were not observed with isomers, substituted analogs, or other fatty acid derivatives. These morphological effects were prevented by blocking protein synthesis or by altering the cytoskeleton with Colcemide or cytochalasin B."} {"id": "PMID:172522", "title": "Effects of adenosine 5'-monophosphate and adenosine 3',5'-cyclic monophosphate on l cells.", "content": "The adenine nucleotides, 5'-AMP and 3',5'-cyclic AMP block L cells in the S-phase of the cell cycle. The intracellular level of cyclic AMP is reduced after incubation of cells with 5'-AMP, and rates of uridine transport are increased after incubation with either 5'-AMP or cyclic AMP. On the contrary, cyclic AMP levels are increased and uridine transport decreased in cells treated with an inhibitor of the cyclic AMP phosphodiesterase. This inhibitor partially reverses the growth-inhibitory effect of cyclic AMP, indicating that a breakdown product is the effective inhibitor of growth. The inhibition of cell growth induced by the adenine nucleotides is prevented by uridine, suggesting that the block in S is due to a lack of availability of pyrimidines.", "contents": "Effects of adenosine 5'-monophosphate and adenosine 3',5'-cyclic monophosphate on l cells. The adenine nucleotides, 5'-AMP and 3',5'-cyclic AMP block L cells in the S-phase of the cell cycle. The intracellular level of cyclic AMP is reduced after incubation of cells with 5'-AMP, and rates of uridine transport are increased after incubation with either 5'-AMP or cyclic AMP. On the contrary, cyclic AMP levels are increased and uridine transport decreased in cells treated with an inhibitor of the cyclic AMP phosphodiesterase. This inhibitor partially reverses the growth-inhibitory effect of cyclic AMP, indicating that a breakdown product is the effective inhibitor of growth. The inhibition of cell growth induced by the adenine nucleotides is prevented by uridine, suggesting that the block in S is due to a lack of availability of pyrimidines."} {"id": "PMID:172523", "title": "Calcium distribution in islets of Langerhans: a study of calcium concentrations and of calcium accumulation in B cell organelles.", "content": "Calcium concentrations of various pancreatic B cell organelles have been determined by X-ray microanalysis of areas of frozen sections of unfixed rat islets of Langerhans. Highest concentrations were detected in storage granules and in mitochondria, although calcium was also present in nuclei, in areas of endoplasmic reticulum and of cytoplasm. Accumulation of 45Ca by isolated organelles has been studied in homogenates and isolated subcellular fractions of rat islets of Langerhans. In the presence of a permeant anion (oxalate or phosphate), accumulation of 45Ca into mitochondria and microsomes was strongly stimulated by ATP. This net uptake was diminished during incubation of homogenates or of a mitochondria plus storage granule-rich fraction in the presence of cyclic AMP, dibutyryl cyclic GMP; 2:4-dinitrophenol or of ruthenium red. Investigations of the characteristics of 45Ca accumulation by homogenates prepared from storage granule-depleted islets showed no differences from those of normal islets, suggesting that the granules do not represent an important labile pool of calcium. With the exception of cyclic AMP and cyclic GMP none of the insulin secretagogues tested (glucose, leucine, arginine, adrenalin, noradrenalin, theophylline, glibenclamide) altered calcium accumulation by islet homogenates. On the basis of absolute calcium levels and of 45Ca uptake studies it is concluded that islet B cells contain a readily exchangeable mitochondrial calcium pool, and an endoplasmic reticulum pool containing a lower concentration of calcium which is also readily exchangeable. The storage granules, despite their high calcium content, do not appear to constitute a labile pool. It seems likely that the labile mitochondria and endoplasmic reticulum pools play a predominant role in the regulation of cytoplasmic free calcium levels, which may in turn be important in the regulation of rates of insulin secretion.", "contents": "Calcium distribution in islets of Langerhans: a study of calcium concentrations and of calcium accumulation in B cell organelles. Calcium concentrations of various pancreatic B cell organelles have been determined by X-ray microanalysis of areas of frozen sections of unfixed rat islets of Langerhans. Highest concentrations were detected in storage granules and in mitochondria, although calcium was also present in nuclei, in areas of endoplasmic reticulum and of cytoplasm. Accumulation of 45Ca by isolated organelles has been studied in homogenates and isolated subcellular fractions of rat islets of Langerhans. In the presence of a permeant anion (oxalate or phosphate), accumulation of 45Ca into mitochondria and microsomes was strongly stimulated by ATP. This net uptake was diminished during incubation of homogenates or of a mitochondria plus storage granule-rich fraction in the presence of cyclic AMP, dibutyryl cyclic GMP; 2:4-dinitrophenol or of ruthenium red. Investigations of the characteristics of 45Ca accumulation by homogenates prepared from storage granule-depleted islets showed no differences from those of normal islets, suggesting that the granules do not represent an important labile pool of calcium. With the exception of cyclic AMP and cyclic GMP none of the insulin secretagogues tested (glucose, leucine, arginine, adrenalin, noradrenalin, theophylline, glibenclamide) altered calcium accumulation by islet homogenates. On the basis of absolute calcium levels and of 45Ca uptake studies it is concluded that islet B cells contain a readily exchangeable mitochondrial calcium pool, and an endoplasmic reticulum pool containing a lower concentration of calcium which is also readily exchangeable. The storage granules, despite their high calcium content, do not appear to constitute a labile pool. It seems likely that the labile mitochondria and endoplasmic reticulum pools play a predominant role in the regulation of cytoplasmic free calcium levels, which may in turn be important in the regulation of rates of insulin secretion."} {"id": "PMID:172525", "title": "Silica gel thin-layer chromatography of acidic phospholipids. II. Chromatographic behaviour of phosphatidylserine and phosphatidic acid applied with different cation composition on adsorbents either free of metal ions or containing a surplus of divalent metal ions.", "content": "Different salt forms of phosphatidylserine and phosphatidic acid (two acidic phospholipids) have been subjected to thin-layer chromatography on two commonly used silica adsorbents, one of which (silica gel HR) is practically free of metal ions and the other (silica gel G) contains 13% of calcium sulphate as binder. The chromatographic behaviour was studied in an acidic, a neutral and a basic solvent. Both adsorbents provided usable systems for phosphatidylserine with each of the three solvents, except for silica gel G with the neutral solvent, in which system tailing was prominent. The inclusion of calcium sulphate in the silica gel tended to impair chromatography of phosphatidylserine in acidic and neutral solvents, but improved its chromatography in the basic solvent. In all the systems, the migration was independent of the cation composition of the applied phosphatidylserine samples. For the chromatography of phosphatidic acid, only three of the systems tested were usable, and in those three, the chromatographic behaviour was independent of the cation composition of the samples. The calcium sulphate in an adsorbent increased tailing of phosphatidic acid in acidic and neutral solvents, as it did for phosphatidylserine, whereas with the basic solvent, calcium sulphate in the adsorbent caused phosphatidic acid to remain at the origin. Two one-dimensional thin-layer chromatographic systems previously recommended for the chromatography of acidic phospholipids were unsuitable for the chromatography of phosphatidic acid under the conditions used here. For both phosphatidylserine and phosphatidic acid chromatographed in acidic systems, the solvent must contain water in addition to acetic acid if excessive tailing is to be avoided.", "contents": "Silica gel thin-layer chromatography of acidic phospholipids. II. Chromatographic behaviour of phosphatidylserine and phosphatidic acid applied with different cation composition on adsorbents either free of metal ions or containing a surplus of divalent metal ions. Different salt forms of phosphatidylserine and phosphatidic acid (two acidic phospholipids) have been subjected to thin-layer chromatography on two commonly used silica adsorbents, one of which (silica gel HR) is practically free of metal ions and the other (silica gel G) contains 13% of calcium sulphate as binder. The chromatographic behaviour was studied in an acidic, a neutral and a basic solvent. Both adsorbents provided usable systems for phosphatidylserine with each of the three solvents, except for silica gel G with the neutral solvent, in which system tailing was prominent. The inclusion of calcium sulphate in the silica gel tended to impair chromatography of phosphatidylserine in acidic and neutral solvents, but improved its chromatography in the basic solvent. In all the systems, the migration was independent of the cation composition of the applied phosphatidylserine samples. For the chromatography of phosphatidic acid, only three of the systems tested were usable, and in those three, the chromatographic behaviour was independent of the cation composition of the samples. The calcium sulphate in an adsorbent increased tailing of phosphatidic acid in acidic and neutral solvents, as it did for phosphatidylserine, whereas with the basic solvent, calcium sulphate in the adsorbent caused phosphatidic acid to remain at the origin. Two one-dimensional thin-layer chromatographic systems previously recommended for the chromatography of acidic phospholipids were unsuitable for the chromatography of phosphatidic acid under the conditions used here. For both phosphatidylserine and phosphatidic acid chromatographed in acidic systems, the solvent must contain water in addition to acetic acid if excessive tailing is to be avoided."} {"id": "PMID:172526", "title": "Solid phase radioimmunoassay for typing herpes simplex viral antibodies in human sera.", "content": "An indirect solid phase radioimmunoassay (RIA) was developed for typing antibody to herpes simplex virus (HSV) types 1 and 2 (HSV-1 and HSV-2) in human sera. The test is based upon absorption of sera with uninfected, HSV-1-infected cells and testing for residual antibody. The high sensitivity of the RIA method for detecting HSV antibody permits examination of sera at high dilutions, and thus relatively small volumes of virus-infected cells are required for cross-absorption of antibodies. Results obtained in RIA typing of HSV antibodies showed good agreement with those obtained by microneutralization and inhibition of passive hemagglutination. The HSV antibody type(s) determined by RIA also showed good correlation with the virus type isolated from the individual, either from clinical specimens or sensory nerve ganglia. The technique was very sensitive for detection and typing of HSV antibdodies in cerebrospinal fluids. The RIA method was highly suitable for detecting two types of HSV antibody in the same serum specimen, and it was possible to show that a marked, type-specific antibody response to HSV-2 does occur in individuals with a primary HSV-2 infection who have experienced a prior infection with HSV-1.", "contents": "Solid phase radioimmunoassay for typing herpes simplex viral antibodies in human sera. An indirect solid phase radioimmunoassay (RIA) was developed for typing antibody to herpes simplex virus (HSV) types 1 and 2 (HSV-1 and HSV-2) in human sera. The test is based upon absorption of sera with uninfected, HSV-1-infected cells and testing for residual antibody. The high sensitivity of the RIA method for detecting HSV antibody permits examination of sera at high dilutions, and thus relatively small volumes of virus-infected cells are required for cross-absorption of antibodies. Results obtained in RIA typing of HSV antibodies showed good agreement with those obtained by microneutralization and inhibition of passive hemagglutination. The HSV antibody type(s) determined by RIA also showed good correlation with the virus type isolated from the individual, either from clinical specimens or sensory nerve ganglia. The technique was very sensitive for detection and typing of HSV antibdodies in cerebrospinal fluids. The RIA method was highly suitable for detecting two types of HSV antibody in the same serum specimen, and it was possible to show that a marked, type-specific antibody response to HSV-2 does occur in individuals with a primary HSV-2 infection who have experienced a prior infection with HSV-1."} {"id": "PMID:172527", "title": "Responses of isolator-derived Japanese quail and quail cell cultures to selected animal viruses.", "content": "Thirteen oncogenic and necrotizing animal viruses were assayed in LIFE Sciences, Inc. (LSI)-specific pathogen-free Japanese quail and LSI-specific pathogen-free chicken embryo cell cultures. Nine viruses produced similar titers in the quail and chicken cell systems, whereas four viruses showed significantly higher titers in chickens. Young Japanese quail and chickens were inoculated with five selected avain viruses and maintained in stainless-steel isolators. Comparable responses were noted in quail and chickens injected with Newcastle disease virus and avain leukosis virus, but quail were significantly more resistant than chickens to fowl pox virus, laryngotracheitis virus, and Marek's disease herpesvirus. Although no overt symptoms of disease were observed in Japanese quail inoculated with most avain viruses, neutralizing antibody or virus was detected, indicating presence of an inapparent infection. In one experiment, neutralizing antibody was detected in a comparable number of quail and chickens after inoculation with avian leukosis virus. Avian leukosis virus viremia was observed at 12 and 70 days postinoculation, with the COFAL (complement fixation for avian leukosis) titers similar for quail and chickens. Most quail infected with Marek's disease herpesvirus produced neutralizing antibody within 70 days but showed no classical symptoms of Marek's disease even when held for 5 months. In contrast, all chickens inoculated with Marek's disease herpesvirus died within 20 days. The utility of quail embryo cell cultured in the preparation of vaccines and biological reagents is discussed.", "contents": "Responses of isolator-derived Japanese quail and quail cell cultures to selected animal viruses. Thirteen oncogenic and necrotizing animal viruses were assayed in LIFE Sciences, Inc. (LSI)-specific pathogen-free Japanese quail and LSI-specific pathogen-free chicken embryo cell cultures. Nine viruses produced similar titers in the quail and chicken cell systems, whereas four viruses showed significantly higher titers in chickens. Young Japanese quail and chickens were inoculated with five selected avain viruses and maintained in stainless-steel isolators. Comparable responses were noted in quail and chickens injected with Newcastle disease virus and avain leukosis virus, but quail were significantly more resistant than chickens to fowl pox virus, laryngotracheitis virus, and Marek's disease herpesvirus. Although no overt symptoms of disease were observed in Japanese quail inoculated with most avain viruses, neutralizing antibody or virus was detected, indicating presence of an inapparent infection. In one experiment, neutralizing antibody was detected in a comparable number of quail and chickens after inoculation with avian leukosis virus. Avian leukosis virus viremia was observed at 12 and 70 days postinoculation, with the COFAL (complement fixation for avian leukosis) titers similar for quail and chickens. Most quail infected with Marek's disease herpesvirus produced neutralizing antibody within 70 days but showed no classical symptoms of Marek's disease even when held for 5 months. In contrast, all chickens inoculated with Marek's disease herpesvirus died within 20 days. The utility of quail embryo cell cultured in the preparation of vaccines and biological reagents is discussed."} {"id": "PMID:172528", "title": "Longitudinal, serological study of cytomegalovirus infections in nurses and in personnel without patient contact.", "content": "Sera were obtained at intervals from 172 hospital employees for measurement of cytomegalovirus (CMV) complement fixation (CF) and indirect hemagglutination antibody. No fourfold rises or falls in titer were seen over a 19- to 27-month period among 71 employees with initially positive CMV CF titers. The concurrence rate between the CMV CF and the indirect hemagglutination antibody tests in identifying seronegative personnel was 96%. Five seroconversions were identified during an average follow-up period of 15 to 17 months per person among 65 pediatric nurses whose CMV CF titers had initially been less than 1:8. No seroconversions were seen during an average follow-up period of 29 months per person among 27 hospitad little patient contact. The rate of acquisition of CMV infections in seronegative pediatric nurses was 4.1 to 7.7% per year. Sera from 9 of the 172 employees studied (5.2%) gave inconsistent results at the lower limits of the CF test.", "contents": "Longitudinal, serological study of cytomegalovirus infections in nurses and in personnel without patient contact. Sera were obtained at intervals from 172 hospital employees for measurement of cytomegalovirus (CMV) complement fixation (CF) and indirect hemagglutination antibody. No fourfold rises or falls in titer were seen over a 19- to 27-month period among 71 employees with initially positive CMV CF titers. The concurrence rate between the CMV CF and the indirect hemagglutination antibody tests in identifying seronegative personnel was 96%. Five seroconversions were identified during an average follow-up period of 15 to 17 months per person among 65 pediatric nurses whose CMV CF titers had initially been less than 1:8. No seroconversions were seen during an average follow-up period of 29 months per person among 27 hospitad little patient contact. The rate of acquisition of CMV infections in seronegative pediatric nurses was 4.1 to 7.7% per year. Sera from 9 of the 172 employees studied (5.2%) gave inconsistent results at the lower limits of the CF test."} {"id": "PMID:172529", "title": "On the mechanisms responsible for the phosphaturia of bicarbonate administration.", "content": "Experiments were carried out in normal dogs to characterize the mechanisms by which sodium bicarbonate administration results in increased excretion of phosphate. Infusion of sodium bicarbonate alone increased fractional phosphate excretion from 0.8 to 29.3%. During bicarbonate administration, ionized calcium fell and mean parathyroid hormone values increased from 59.6 to 230.4 muleq/ml. In the same group of dogs, administration of sodium bicarbonate plus calcium prevented the fall in ionized calcium, and parathyroid hormone levels remained unchanged. In these dogs fractional phosphate excretion increased from 2.4 to only 4.9%. Similar results were obtained in thyroparathyroidectomized dogs receiving sodium bicarbonate. In these dogs fractional excretion of phosphate increased from 0.6 to 4.5%. Under all three experimental conditions no differences were observed in sodium or bicarbonate excretion or in urinary or plasma pH. Administration of hydrochloric acid, after phosphaturia had been induced by the infusion of bicarbonate, resulted in a decrease in plasma bicarbonate and an acid urine; however, the phosphaturia persisted even in the presence of an acid urine pH. In five thyroparathyroidectomized dogs infused with parathyroid hormone throughout, administration of identical amounts of sodium as either NaCl or NaHCO3 resulted in a similar degree of phosphaturia despite significant differences in urine pH. These experiments suggest that a rise in parathyroid hormone levels, resulting from a fall in ionized calcium, is the major mechanism by which bicarbonate administration produces phosphaturia. An increased natriuresis per nephron, as a consequence of extracellular fluid volume expansion, contributes to the phosphaturia. On the other hand, alkalinization of the urine does not play a significant role in the phosphaturia seen after bicarbonate administration.", "contents": "On the mechanisms responsible for the phosphaturia of bicarbonate administration. Experiments were carried out in normal dogs to characterize the mechanisms by which sodium bicarbonate administration results in increased excretion of phosphate. Infusion of sodium bicarbonate alone increased fractional phosphate excretion from 0.8 to 29.3%. During bicarbonate administration, ionized calcium fell and mean parathyroid hormone values increased from 59.6 to 230.4 muleq/ml. In the same group of dogs, administration of sodium bicarbonate plus calcium prevented the fall in ionized calcium, and parathyroid hormone levels remained unchanged. In these dogs fractional phosphate excretion increased from 2.4 to only 4.9%. Similar results were obtained in thyroparathyroidectomized dogs receiving sodium bicarbonate. In these dogs fractional excretion of phosphate increased from 0.6 to 4.5%. Under all three experimental conditions no differences were observed in sodium or bicarbonate excretion or in urinary or plasma pH. Administration of hydrochloric acid, after phosphaturia had been induced by the infusion of bicarbonate, resulted in a decrease in plasma bicarbonate and an acid urine; however, the phosphaturia persisted even in the presence of an acid urine pH. In five thyroparathyroidectomized dogs infused with parathyroid hormone throughout, administration of identical amounts of sodium as either NaCl or NaHCO3 resulted in a similar degree of phosphaturia despite significant differences in urine pH. These experiments suggest that a rise in parathyroid hormone levels, resulting from a fall in ionized calcium, is the major mechanism by which bicarbonate administration produces phosphaturia. An increased natriuresis per nephron, as a consequence of extracellular fluid volume expansion, contributes to the phosphaturia. On the other hand, alkalinization of the urine does not play a significant role in the phosphaturia seen after bicarbonate administration."} {"id": "PMID:172530", "title": "Metabolism of apoprotein B of plasma very low density lipoproteins in the rat.", "content": "As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat.", "contents": "Metabolism of apoprotein B of plasma very low density lipoproteins in the rat. As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat."} {"id": "PMID:172531", "title": "Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia.", "content": "The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt. The results were compared with those of similar studies simultaneously performed in untreated patients with the heterozygous form of FH and with the results of earlier studies performed on normolipidemic subjects. Before shunt surgery, the rate of synthesis of LDL in the FH homozygote (mg/kg per day) was fourfold higher than in normolipidemic subjects and twofold higher than in her heterozygous mother. The fractional catabolic rate for LDL in the homozygote was decreased to 33% of normal control values. The rate of cholesterol synthesis, estimated by chemical sterol balance, was higher in the FH homozygote than in two FH heterozygotes of similar age studied simultaneously. When considered in relation to the markedly elevated level of plasma cholesterol, the observed rate of cholesterol synthesis in the FH homozygote was inappropriately elevated. Bile acid production was normal in all three children. 5 mo after shunt surgery, the rate of LDL synthesis in the homozygote had declined by 48% as compared with the preoperative value, and this caused a 39% drop in the plasma LDL cholesterol level despite a 17% reduction in the fractional catabolic rate of the lipoprotein. The rate of cholesterol synthesis fell by 62% as compared with the preoperative value. The findings of an inappropriately elevated rate of production of both cholesterol and LDL as well as a reduced fractional catabolic rate for the lipoprotein in the untreated FH homozygote are consistent with results of studies in cultured fibroblasts indicating that the primary genetic defect in FH involves a deficiency in a cell-surface receptor for LDL that regulates both cholesterol synthesis and LDL degradation. Although the mechanism for the decline in production of cholesterol and LDL after portacaval shunt surgery is unknown, it was observed that these changes were associated with marked increases in the plasma concentrations of bile acids and glucagon.", "contents": "Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia. The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt. The results were compared with those of similar studies simultaneously performed in untreated patients with the heterozygous form of FH and with the results of earlier studies performed on normolipidemic subjects. Before shunt surgery, the rate of synthesis of LDL in the FH homozygote (mg/kg per day) was fourfold higher than in normolipidemic subjects and twofold higher than in her heterozygous mother. The fractional catabolic rate for LDL in the homozygote was decreased to 33% of normal control values. The rate of cholesterol synthesis, estimated by chemical sterol balance, was higher in the FH homozygote than in two FH heterozygotes of similar age studied simultaneously. When considered in relation to the markedly elevated level of plasma cholesterol, the observed rate of cholesterol synthesis in the FH homozygote was inappropriately elevated. Bile acid production was normal in all three children. 5 mo after shunt surgery, the rate of LDL synthesis in the homozygote had declined by 48% as compared with the preoperative value, and this caused a 39% drop in the plasma LDL cholesterol level despite a 17% reduction in the fractional catabolic rate of the lipoprotein. The rate of cholesterol synthesis fell by 62% as compared with the preoperative value. The findings of an inappropriately elevated rate of production of both cholesterol and LDL as well as a reduced fractional catabolic rate for the lipoprotein in the untreated FH homozygote are consistent with results of studies in cultured fibroblasts indicating that the primary genetic defect in FH involves a deficiency in a cell-surface receptor for LDL that regulates both cholesterol synthesis and LDL degradation. Although the mechanism for the decline in production of cholesterol and LDL after portacaval shunt surgery is unknown, it was observed that these changes were associated with marked increases in the plasma concentrations of bile acids and glucagon."} {"id": "PMID:172532", "title": "Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates.", "content": "The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis.", "contents": "Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates. The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis."} {"id": "PMID:172533", "title": "Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects.", "content": "The interrelationship between apolipoprotein B in very low density lipoprotein (VLDL-B) and in low density lipoprotein (LDL-B) was studied in seven normal and hyperlipidemic men and women, with purified radioiodinated VLDL. The time-course of the appearance of radioactivity in LDL was followed. As the specific activity curves intersected at the masimal height of the LDL-B curve, it was inferred that all or most LDL-B peptide is derived from VLDL-B peptide. This transfer was further quantitated in seven normotriglyceridemic subjects by simultaneous i.v. injection of purified 131I-VLDL and 125I-LDL. By a deconvolution method, a quantitative description of the rate of entry of 131Ivldl-b into 131I-LDL-B was derived by analysis of 131I-LDL-B and 125I-ldl-b radioactivity in plasma. The results indicate that approximately 90% of VLDL-B mass is converted into LDL-B in subjects with normal serum triglyceride concentrations. The synthetic rates of VLDL-B and LDL-B peptide were simultaneously measured in six normal subjects, and two patients with heterozygous familial hypercholesterolemia (type IIa). The turnover rates for VLDL-B and LDL-B peptide were similar in these subjects. The findings in the three parts of this study were consistent with the view that most if not all VLDL-B is converted into LDL-B peptide, and most if not all LDL-B is derived from VLDL-B peptide in normotriglyceridemic subjects.", "contents": "Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. The interrelationship between apolipoprotein B in very low density lipoprotein (VLDL-B) and in low density lipoprotein (LDL-B) was studied in seven normal and hyperlipidemic men and women, with purified radioiodinated VLDL. The time-course of the appearance of radioactivity in LDL was followed. As the specific activity curves intersected at the masimal height of the LDL-B curve, it was inferred that all or most LDL-B peptide is derived from VLDL-B peptide. This transfer was further quantitated in seven normotriglyceridemic subjects by simultaneous i.v. injection of purified 131I-VLDL and 125I-LDL. By a deconvolution method, a quantitative description of the rate of entry of 131Ivldl-b into 131I-LDL-B was derived by analysis of 131I-LDL-B and 125I-ldl-b radioactivity in plasma. The results indicate that approximately 90% of VLDL-B mass is converted into LDL-B in subjects with normal serum triglyceride concentrations. The synthetic rates of VLDL-B and LDL-B peptide were simultaneously measured in six normal subjects, and two patients with heterozygous familial hypercholesterolemia (type IIa). The turnover rates for VLDL-B and LDL-B peptide were similar in these subjects. The findings in the three parts of this study were consistent with the view that most if not all VLDL-B is converted into LDL-B peptide, and most if not all LDL-B is derived from VLDL-B peptide in normotriglyceridemic subjects."} {"id": "PMID:172534", "title": "Apoprotein composition of very low density lipoproteins of human serum.", "content": "Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons.", "contents": "Apoprotein composition of very low density lipoproteins of human serum. Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons."} {"id": "PMID:172535", "title": "The diagnosis of mucopolysaccharidoses by electron microscopy of skin biopsies.", "content": "An ultrastructural examination was carried out on the skin of six children suffering from Mucopolysaccharidosis I (MPSI or Hurler's disease) and MPS II (Hunter's disease). Both intracellular mucopolysaccharides and lipids were observed. The dermal cells, i.e. fibroblasts, macrophages, were loaded with multiple vacuolar inclusions thought to be of lysosomal origin. They appeared either content-free or filled with granular, fuzzy and/or pseudomyelinic structures. Identical abnormalities were observed within the Schwann cells, smooth muscle cells and keratinocytes. Mast cells showed peculiar \"worm-like\" inclusions apart from their normal granulations. Since ultrastructure of a skin sample may provide as much data as brain, liver or kidney, cutaneous electron microscopy can be recommended to confirm a diagnosis of MPS.", "contents": "The diagnosis of mucopolysaccharidoses by electron microscopy of skin biopsies. An ultrastructural examination was carried out on the skin of six children suffering from Mucopolysaccharidosis I (MPSI or Hurler's disease) and MPS II (Hunter's disease). Both intracellular mucopolysaccharides and lipids were observed. The dermal cells, i.e. fibroblasts, macrophages, were loaded with multiple vacuolar inclusions thought to be of lysosomal origin. They appeared either content-free or filled with granular, fuzzy and/or pseudomyelinic structures. Identical abnormalities were observed within the Schwann cells, smooth muscle cells and keratinocytes. Mast cells showed peculiar \"worm-like\" inclusions apart from their normal granulations. Since ultrastructure of a skin sample may provide as much data as brain, liver or kidney, cutaneous electron microscopy can be recommended to confirm a diagnosis of MPS."} {"id": "PMID:172536", "title": "Plasma adrenocorticoid response to corticotropin in dairy cattle fed high silage diets.", "content": "Responses of plasma corticoids to adrenocorticotropic hormone (.32 U/kg body weight) administered during early lactation were measured in dairy cattle consuming large amounts of concentrate feeds and one of the following forage diets: alfalfa-timothy hay plus corn silage, alfalfa-timothy hay crop silage plus corn silage, or corn silage. Concentrations of plasma corticoids increased to maximum in all groups within 60 to 90 min. Concentrations remained at near maximum for 4 to 5 h and then declined to baseline. Maximum corticoid concentrations following adrenocorticotropic hormone injection differed among forage treatment groups. Responses of corn silage and hay crop silage groups (46.7 +/- 1.1 and 50.1 +/- 2.4 ng/ml) did not differ but were less than those in the hay group (65.5 +/- 2.9 ng/ml). Response measured as area under the curve of plasma corticoid response also differed among forage treatments: hay 443 +/- 17 h (ng/ml) is greater than hay crop silage 334 +/- 34 is greater than corn silage 245 +/- 36. Results are discussed in terms of stress susceptibility in dairy cattle consuming diets containing large amounts of silage.", "contents": "Plasma adrenocorticoid response to corticotropin in dairy cattle fed high silage diets. Responses of plasma corticoids to adrenocorticotropic hormone (.32 U/kg body weight) administered during early lactation were measured in dairy cattle consuming large amounts of concentrate feeds and one of the following forage diets: alfalfa-timothy hay plus corn silage, alfalfa-timothy hay crop silage plus corn silage, or corn silage. Concentrations of plasma corticoids increased to maximum in all groups within 60 to 90 min. Concentrations remained at near maximum for 4 to 5 h and then declined to baseline. Maximum corticoid concentrations following adrenocorticotropic hormone injection differed among forage treatment groups. Responses of corn silage and hay crop silage groups (46.7 +/- 1.1 and 50.1 +/- 2.4 ng/ml) did not differ but were less than those in the hay group (65.5 +/- 2.9 ng/ml). Response measured as area under the curve of plasma corticoid response also differed among forage treatments: hay 443 +/- 17 h (ng/ml) is greater than hay crop silage 334 +/- 34 is greater than corn silage 245 +/- 36. Results are discussed in terms of stress susceptibility in dairy cattle consuming diets containing large amounts of silage."} {"id": "PMID:172540", "title": "How the human brain responds to aging.", "content": "The characteristic morphologic changes frequently observed in the brain of an old adult include a decrease in weight and volume, a change in the pattern of cerebral cortical convolutions, and an increase in ventricular size. Cell loss varies from region to region in the brain, and may be intensified in Alzheimer's disease and other disorders associated with senile dementia. Among the neuroglial cells, the microglia undergo the most significant changes with age. Although senile brain disease previously has been regarded as secondary to atherosclerosis, recent neuropathologic studies indicate that only 30 to 40 percent of senile brain disease arises from cerebrovascular pathologic lesions. The dilemma remains, however, of how much of the deterioration observed in the aged is related to disease and how much to senescence. The interaction between gene expression and environmental conditions in aging is another important question for the geriatrician. Progress in the control and treatment of disorders associated with old age depends upon further research into the mechanisms that underlie the process of aging in the brain.", "contents": "How the human brain responds to aging. The characteristic morphologic changes frequently observed in the brain of an old adult include a decrease in weight and volume, a change in the pattern of cerebral cortical convolutions, and an increase in ventricular size. Cell loss varies from region to region in the brain, and may be intensified in Alzheimer's disease and other disorders associated with senile dementia. Among the neuroglial cells, the microglia undergo the most significant changes with age. Although senile brain disease previously has been regarded as secondary to atherosclerosis, recent neuropathologic studies indicate that only 30 to 40 percent of senile brain disease arises from cerebrovascular pathologic lesions. The dilemma remains, however, of how much of the deterioration observed in the aged is related to disease and how much to senescence. The interaction between gene expression and environmental conditions in aging is another important question for the geriatrician. Progress in the control and treatment of disorders associated with old age depends upon further research into the mechanisms that underlie the process of aging in the brain."} {"id": "PMID:172537", "title": "Production of a nonwettable enamel surface.", "content": "A water-repellent enamel surface was achieved using a new material that is a combination of fumed silicon dioxide and a silane. The effects of this coating on enamel were studied. In vitro studies suggest that the material produces good water and saliva repellency. However, no reduction in bacterial colonization between treated and control enamel occurred. results of in vivo investigations of coated and control Styroflex strips showed a reduction in deposits on the former. Retention with or without previous acid etching of the enamel was poor.", "contents": "Production of a nonwettable enamel surface. A water-repellent enamel surface was achieved using a new material that is a combination of fumed silicon dioxide and a silane. The effects of this coating on enamel were studied. In vitro studies suggest that the material produces good water and saliva repellency. However, no reduction in bacterial colonization between treated and control enamel occurred. results of in vivo investigations of coated and control Styroflex strips showed a reduction in deposits on the former. Retention with or without previous acid etching of the enamel was poor."} {"id": "PMID:172550", "title": "[Radiography of breast cancers].", "content": "Malignant tumor in the breast create a stroma-reaction that gives the typical aspect of malignant picture with retractile fibrosis, oedema and microcalcifications (10 to 15%). The diagnosis is really uncertain in only 2% of the cases. Cytology after fine needle puncture permit the diagnosis.", "contents": "[Radiography of breast cancers]. Malignant tumor in the breast create a stroma-reaction that gives the typical aspect of malignant picture with retractile fibrosis, oedema and microcalcifications (10 to 15%). The diagnosis is really uncertain in only 2% of the cases. Cytology after fine needle puncture permit the diagnosis."} {"id": "PMID:172551", "title": "[Viruses and mammary carcinogenesis].", "content": "Bittner virus has been extensively studied by recent electron microscopy and molecular biology techniques. The structure, the biochemical, physical and antigenic properties of the RNA tumor viruses - i.e. the mouse mammary tumor virus (MMTV) - are well known. Recent observations in human tissues of particles similar to animal viruses that are known to be oncogenic have raised the hypothesis of the role of viruses in human cancer. In mice, breast cancer can be caused by a virus - the Bittner virus or MMTV - that is usually transmitted from mother to offspring in the milk. The discovery of such virus particles in human milks and breast cancer tissues could provide data about a viral aetiology of human breast cancer.", "contents": "[Viruses and mammary carcinogenesis]. Bittner virus has been extensively studied by recent electron microscopy and molecular biology techniques. The structure, the biochemical, physical and antigenic properties of the RNA tumor viruses - i.e. the mouse mammary tumor virus (MMTV) - are well known. Recent observations in human tissues of particles similar to animal viruses that are known to be oncogenic have raised the hypothesis of the role of viruses in human cancer. In mice, breast cancer can be caused by a virus - the Bittner virus or MMTV - that is usually transmitted from mother to offspring in the milk. The discovery of such virus particles in human milks and breast cancer tissues could provide data about a viral aetiology of human breast cancer."} {"id": "PMID:172552", "title": "[Hormonal receptors of malignant breast tumors].", "content": "Tissue samples from 166 primary and 136 metastatic breast cancers were analysed for the presence of estrogen receptors. It was found by measuring the affinity of the cytoplasmic fraction of these samples for 3H-estradiol-17 beta that receptors were present in 72 p. 100 and 54 p. 100 of primary and metastatic cancers respectively. Receptor concentration varied among sample in an apparently continuous distribution from zero to 2,080 femtomoles per mg tissue protein. This suggests that mammary tumors are different from one another more in a quantitative than in a qualitative way. Detectable amounts of receptors were found in samples from mammary dysplasia, fibroadenomas as well as from one papilloma; none was detected in samples from non-tumorous mammary gland, nipple areola or skin. At mastectomy, no correlation was found between presence or absence of receptors in the primary tumors, and presence or absence of metastatic axillary nodes. On the other hand both the primary and its axillary metastases almost always displayed the same characteristic as far as presence or absence of receptors was concerned. Analysis of clinical studies reported seems to indicate that women with advanced breast cancer respond in a fair proportion of cases to various endocrine treatments when tumor tissue biopsies contain estrogen receptors whereas the probability of a response is very low in their absence.", "contents": "[Hormonal receptors of malignant breast tumors]. Tissue samples from 166 primary and 136 metastatic breast cancers were analysed for the presence of estrogen receptors. It was found by measuring the affinity of the cytoplasmic fraction of these samples for 3H-estradiol-17 beta that receptors were present in 72 p. 100 and 54 p. 100 of primary and metastatic cancers respectively. Receptor concentration varied among sample in an apparently continuous distribution from zero to 2,080 femtomoles per mg tissue protein. This suggests that mammary tumors are different from one another more in a quantitative than in a qualitative way. Detectable amounts of receptors were found in samples from mammary dysplasia, fibroadenomas as well as from one papilloma; none was detected in samples from non-tumorous mammary gland, nipple areola or skin. At mastectomy, no correlation was found between presence or absence of receptors in the primary tumors, and presence or absence of metastatic axillary nodes. On the other hand both the primary and its axillary metastases almost always displayed the same characteristic as far as presence or absence of receptors was concerned. Analysis of clinical studies reported seems to indicate that women with advanced breast cancer respond in a fair proportion of cases to various endocrine treatments when tumor tissue biopsies contain estrogen receptors whereas the probability of a response is very low in their absence."} {"id": "PMID:172553", "title": "[Histological classification of malignant breast neoplasms. Recent concepts].", "content": "The recent histological classifications of breast malignant epithelial tumours place increased emphasis on several concepts: in situ carcinoma, difference of lobular carcinoma from other forms of breast cancer and histological factors of prognosis. The authors propose to discriminate: non infiltrating duct carcinoma (intraductal carcinoma); lobular carcinoma (in situ and infiltrating); infiltrating duct carcinoma in their usual form (80 p. 100 about of all breast carcinoma); among them, histological types with a less ominous prognosis, although relatively rare, are stressed (infiltrating papillary and comedo-carcinomas, tubular carcinoma, medullary carcinoma, colloid carcinoma, cylindroma, certain metaplastic variants, Paget's disease of the nipple); some features in unusual hosts are related. They mention the criteria of the Scarff and Bloom's \"grading\" and its importance from the point of view of prognosis, mainly for the usual infiltrating forms. Other malignant tumours of the breast (malignant cystosarcoma phyllodes, sarcomas, mammary metastases) are more scarcely seen (I p. 100 of the mammary neoplasms): their classification is succinctly recalled.", "contents": "[Histological classification of malignant breast neoplasms. Recent concepts]. The recent histological classifications of breast malignant epithelial tumours place increased emphasis on several concepts: in situ carcinoma, difference of lobular carcinoma from other forms of breast cancer and histological factors of prognosis. The authors propose to discriminate: non infiltrating duct carcinoma (intraductal carcinoma); lobular carcinoma (in situ and infiltrating); infiltrating duct carcinoma in their usual form (80 p. 100 about of all breast carcinoma); among them, histological types with a less ominous prognosis, although relatively rare, are stressed (infiltrating papillary and comedo-carcinomas, tubular carcinoma, medullary carcinoma, colloid carcinoma, cylindroma, certain metaplastic variants, Paget's disease of the nipple); some features in unusual hosts are related. They mention the criteria of the Scarff and Bloom's \"grading\" and its importance from the point of view of prognosis, mainly for the usual infiltrating forms. Other malignant tumours of the breast (malignant cystosarcoma phyllodes, sarcomas, mammary metastases) are more scarcely seen (I p. 100 of the mammary neoplasms): their classification is succinctly recalled."} {"id": "PMID:172554", "title": "Enzyme cytochemistry of Candida albicans.", "content": "The application of a new preparation method for demonstrating the activities of hydrolytic and oxidative enzymes in Candida albicans is reported. The problem of inadequate penetration of fixatives into yeast cells has been solved by sectioning solidified pellets of the cells in the presence of glutaraldehyde, a procedure that yields a fairly well preserved ultrastructure and sufficient enzyme activities. The subcellular distribution of most specific and nonspecific phosphatases and of peroxidases is at variance with that found in mammalian cells. The activities toward beta-glycerophosphate, p-nitrophenylphosphate, adenosine triphosphate, adenosine monophosphate, thiamine pyrophosphate and glucose 6-phosphate are almost exclusively confined to the central vacuolar apparatus. Oxidative and peroxidative activities are demonstrated only in mitochondria. Specific marker enzymes for endoplasmic reticulum, plasmalemma, Golgi apparatus and peroxisomes in C. albicans are not found. The possible function of the various subcellular organelles in relation to their enzymatic content is discussed.", "contents": "Enzyme cytochemistry of Candida albicans. The application of a new preparation method for demonstrating the activities of hydrolytic and oxidative enzymes in Candida albicans is reported. The problem of inadequate penetration of fixatives into yeast cells has been solved by sectioning solidified pellets of the cells in the presence of glutaraldehyde, a procedure that yields a fairly well preserved ultrastructure and sufficient enzyme activities. The subcellular distribution of most specific and nonspecific phosphatases and of peroxidases is at variance with that found in mammalian cells. The activities toward beta-glycerophosphate, p-nitrophenylphosphate, adenosine triphosphate, adenosine monophosphate, thiamine pyrophosphate and glucose 6-phosphate are almost exclusively confined to the central vacuolar apparatus. Oxidative and peroxidative activities are demonstrated only in mitochondria. Specific marker enzymes for endoplasmic reticulum, plasmalemma, Golgi apparatus and peroxisomes in C. albicans are not found. The possible function of the various subcellular organelles in relation to their enzymatic content is discussed."} {"id": "PMID:172555", "title": "Ultrastructural visualization of virus-induced surface antigens. Comparative studies of three immunohistochemical techniques.", "content": "Three immunohistochemical techniques used for ultrastructural localization of cell surface antigens were compared with respect to ease of reagent preparation and qualitative aspects of cell surface staining. The techniques compared were: (a) ferritin-conjugated antibody, (b) \"hybrid\" antibody and (c) a modification of the \"bridging\" technique which employs soluble immune complexes. Used in conjuction with strain MC29 avian oncornavirus-infected chick embryo cells and chicken antiviral immune serum, the results of all three techniques were comparable. In terms of ease of preparation, the \"bridging\" technique employing soluble complexes was found to be the most satisfactory.", "contents": "Ultrastructural visualization of virus-induced surface antigens. Comparative studies of three immunohistochemical techniques. Three immunohistochemical techniques used for ultrastructural localization of cell surface antigens were compared with respect to ease of reagent preparation and qualitative aspects of cell surface staining. The techniques compared were: (a) ferritin-conjugated antibody, (b) \"hybrid\" antibody and (c) a modification of the \"bridging\" technique which employs soluble immune complexes. Used in conjuction with strain MC29 avian oncornavirus-infected chick embryo cells and chicken antiviral immune serum, the results of all three techniques were comparable. In terms of ease of preparation, the \"bridging\" technique employing soluble complexes was found to be the most satisfactory."} {"id": "PMID:172556", "title": "The distribution of collagenase in normal rat tissues.", "content": "A rabbit monospecific anti-rat uterus collagenase antibody has been used to study the distribution of collagenase in normal rat tissues by immunohistochemical methods. Indirect staining was performed with fluorescein-conjugated goat anti-rabbit immunoglobulin G antibody. The organs studied were brain, lung, myocardium, liver, spleen, kidney, adrenal, testes, uterus, xiphoid cartilage, tail tendon, skeletal (triceps) muscle and skin. Collagenase is widely present throughout the connective tissue structures in all organs examined. The enzyme is apparently bound to collagen fibers, reticulum fibers and basement membranes. The results suggest that control of collagenase activity depends on factors other than the presence of the enzyme in tissues.", "contents": "The distribution of collagenase in normal rat tissues. A rabbit monospecific anti-rat uterus collagenase antibody has been used to study the distribution of collagenase in normal rat tissues by immunohistochemical methods. Indirect staining was performed with fluorescein-conjugated goat anti-rabbit immunoglobulin G antibody. The organs studied were brain, lung, myocardium, liver, spleen, kidney, adrenal, testes, uterus, xiphoid cartilage, tail tendon, skeletal (triceps) muscle and skin. Collagenase is widely present throughout the connective tissue structures in all organs examined. The enzyme is apparently bound to collagen fibers, reticulum fibers and basement membranes. The results suggest that control of collagenase activity depends on factors other than the presence of the enzyme in tissues."} {"id": "PMID:172557", "title": "Intracellular localization and size of glycogen particles in glycogen synthesized under histochemical conditions.", "content": "During the investigation of the histochemical synthesis of glycogen particles from glucose 1-phosphate by the phosphorylase-branching glycosyltransferase system in various tissue cells, it was observed that focal synthesis localized in a certain area of the cytoplasm occurred in some cells. This differed from the usual synthesis in which particles of similar size were synthesized within the cytoplasm. Otherwise, cytoplasmic particles of various size were also synthesized in other cells under the same histochemical condition. The possible significance of the presence of these patterns in glycogen synthesis is discussed.", "contents": "Intracellular localization and size of glycogen particles in glycogen synthesized under histochemical conditions. During the investigation of the histochemical synthesis of glycogen particles from glucose 1-phosphate by the phosphorylase-branching glycosyltransferase system in various tissue cells, it was observed that focal synthesis localized in a certain area of the cytoplasm occurred in some cells. This differed from the usual synthesis in which particles of similar size were synthesized within the cytoplasm. Otherwise, cytoplasmic particles of various size were also synthesized in other cells under the same histochemical condition. The possible significance of the presence of these patterns in glycogen synthesis is discussed."} {"id": "PMID:172558", "title": "Variation among strains of type A foot-and-mouth disease virus in the Eastern Mediterranean region 1964-1972.", "content": "Variants of type A FMD virus from the Eastern Mediterranean region over the years 1964-72 have been shown to belong to a group distinct from the Western European strains as represented by A5 Westerwald. This group appears to derive from the A22 strain first recognized in 1964 and indicates the possibility of new strains supplanting old in the field.", "contents": "Variation among strains of type A foot-and-mouth disease virus in the Eastern Mediterranean region 1964-1972. Variants of type A FMD virus from the Eastern Mediterranean region over the years 1964-72 have been shown to belong to a group distinct from the Western European strains as represented by A5 Westerwald. This group appears to derive from the A22 strain first recognized in 1964 and indicates the possibility of new strains supplanting old in the field."} {"id": "PMID:172559", "title": "A solid phase micro-radioimmunoassay to detect minute amounts of Ig class specific anti-viral antibody in a mouse model system.", "content": "A simple and rapid micro-radioimmunoassay was developed to detect and quantitate class specific mouse anti-Sendai virus antibodies. Two different 125I-labelled indicator systems were studied. After incubation of test serum with antigen one system used 125I-rabbit anti-mouse IgG (RIA 1) and the second employed rabbit anti-mouse IgG, IgA or IgM followed by 125I-sheep anti-rabbit immunoglobulin reagent (RIA 2). The RIA 2 method was adopted for routine use as it was more sensitive, gave better discrimination between sample and background counts and eliminated the need for several labelled rabbit anti-mouse Ig class specific antisera. The technique was found to be about 100 times more sensitive than conventional HI tests, specific, reliable and economical of reagents and time.", "contents": "A solid phase micro-radioimmunoassay to detect minute amounts of Ig class specific anti-viral antibody in a mouse model system. A simple and rapid micro-radioimmunoassay was developed to detect and quantitate class specific mouse anti-Sendai virus antibodies. Two different 125I-labelled indicator systems were studied. After incubation of test serum with antigen one system used 125I-rabbit anti-mouse IgG (RIA 1) and the second employed rabbit anti-mouse IgG, IgA or IgM followed by 125I-sheep anti-rabbit immunoglobulin reagent (RIA 2). The RIA 2 method was adopted for routine use as it was more sensitive, gave better discrimination between sample and background counts and eliminated the need for several labelled rabbit anti-mouse Ig class specific antisera. The technique was found to be about 100 times more sensitive than conventional HI tests, specific, reliable and economical of reagents and time."} {"id": "PMID:172560", "title": "An evaluation of adenosine 3',5'-cyclic monophospate-dependent protein kinase activity in atopic dermatitis.", "content": "Activity of adenosine 3',5'-cyclic monophosphate-dependent protein kinase has been measured in the skin of normal controls, patients with non-atopic skin disorders, and those with atopic dermatitis. All samples analyzed displayed the presence of this enzymatic activity. However, the enzyme from the atopic skin did not seem to be dependent on cyclic AMP for activity. Whether this is due to an artifact of isolation of protein kinase or is indeed the true in vivo nature of the enzyme remains to be established.", "contents": "An evaluation of adenosine 3',5'-cyclic monophospate-dependent protein kinase activity in atopic dermatitis. Activity of adenosine 3',5'-cyclic monophosphate-dependent protein kinase has been measured in the skin of normal controls, patients with non-atopic skin disorders, and those with atopic dermatitis. All samples analyzed displayed the presence of this enzymatic activity. However, the enzyme from the atopic skin did not seem to be dependent on cyclic AMP for activity. Whether this is due to an artifact of isolation of protein kinase or is indeed the true in vivo nature of the enzyme remains to be established."} {"id": "PMID:172561", "title": "Human responses to two decavalent rhinovirus vaccines.", "content": "Two formalin-inactivated, decavalent rhinovirus vaccines were tested in humans for acceptability and antigenicity. Infectivity titers of the vaccine antigens were low and ranged from 10(1.5) to 10(5.5) 50% tissue culture infective doses/ml. There were minimal or no side effects to either vaccine. The first inoculation of one vaccine produced antigenic responses to 30% of the administered antigens. Limited testing for heterologous antibody responses to nonvaccine antigens showed scattered responses. These findings suggest that potent multivalent rhinovirus vaccines containing antigens selected for cross-reactivity should be tested in an attempt to develop practical control measures for rhinoviruses.", "contents": "Human responses to two decavalent rhinovirus vaccines. Two formalin-inactivated, decavalent rhinovirus vaccines were tested in humans for acceptability and antigenicity. Infectivity titers of the vaccine antigens were low and ranged from 10(1.5) to 10(5.5) 50% tissue culture infective doses/ml. There were minimal or no side effects to either vaccine. The first inoculation of one vaccine produced antigenic responses to 30% of the administered antigens. Limited testing for heterologous antibody responses to nonvaccine antigens showed scattered responses. These findings suggest that potent multivalent rhinovirus vaccines containing antigens selected for cross-reactivity should be tested in an attempt to develop practical control measures for rhinoviruses."} {"id": "PMID:172562", "title": "Humoral and cellular immune responses to an envelope-associated antigen of herpes simplex virus.", "content": "The humoral and cellular immune responses of rabbits and guinea pigs to the envelope-associated antigen of herpes simplex virus type I were studied. Neutralizing antibody (at high titer) and lymphocytes reactive to herpes simplex virus were detected in both guinea pigs and rabbits after immunization with the antigen. In a standard assay of cellular immunity to herpes simplex virus, the antigen stimulated blast transformation of herpes simplex virus-reactive splenic lymphocytes in vitro. Furthermore, immunization of rabbits with the envelope-associated antigen protected the animals from a lethal dose of live herpes simplex virus. Thus an antigen of herpes simplex virus can be prepared which contains neither infectious nor noninfectious viral particles and which stimulates immunity to the virus in laboratory animals.", "contents": "Humoral and cellular immune responses to an envelope-associated antigen of herpes simplex virus. The humoral and cellular immune responses of rabbits and guinea pigs to the envelope-associated antigen of herpes simplex virus type I were studied. Neutralizing antibody (at high titer) and lymphocytes reactive to herpes simplex virus were detected in both guinea pigs and rabbits after immunization with the antigen. In a standard assay of cellular immunity to herpes simplex virus, the antigen stimulated blast transformation of herpes simplex virus-reactive splenic lymphocytes in vitro. Furthermore, immunization of rabbits with the envelope-associated antigen protected the animals from a lethal dose of live herpes simplex virus. Thus an antigen of herpes simplex virus can be prepared which contains neither infectious nor noninfectious viral particles and which stimulates immunity to the virus in laboratory animals."} {"id": "PMID:172563", "title": "Experimental horizontal transmission of Herpesvirus saimiri from squirrel monkeys to an owl monkey.", "content": "Herpesvirus saimiri was naturally transmitted from squirrel monkeys excreting the virus to one of two owl monkeys housed in the same cage. The owl monkey became infected approximately three months after contact was initiated. H. saimiri was consistently isolated from the peripheral lymphocytes until this animal died eight months later. During this period the owl monkey developed specific antibody to H. saimiri to a maximal neutralization index of 5.5 logs. The other monkey remained uninfected for an ovservation period of one year. The documentation of this horizontal transmission of H. saimiri infection from squirrel monkeys to an owl monkey suggests that owl monkeys developing spontaneous malignant lymphomas associated with H. saimiri infection may also have acquired the infection in this manner.", "contents": "Experimental horizontal transmission of Herpesvirus saimiri from squirrel monkeys to an owl monkey. Herpesvirus saimiri was naturally transmitted from squirrel monkeys excreting the virus to one of two owl monkeys housed in the same cage. The owl monkey became infected approximately three months after contact was initiated. H. saimiri was consistently isolated from the peripheral lymphocytes until this animal died eight months later. During this period the owl monkey developed specific antibody to H. saimiri to a maximal neutralization index of 5.5 logs. The other monkey remained uninfected for an ovservation period of one year. The documentation of this horizontal transmission of H. saimiri infection from squirrel monkeys to an owl monkey suggests that owl monkeys developing spontaneous malignant lymphomas associated with H. saimiri infection may also have acquired the infection in this manner."} {"id": "PMID:172569", "title": "Adaptive enhancement of amino acid transport in human leukemia leukocytes: studies with alpha-aminoisobutyric acid.", "content": "Initial rates of accumulation (Vi) of [3-14C] alpha-aminoisobutyric acid (AIB) by human leukemic leukocytes increased markedly and progressively during 240 minute incubations in amino acid-deficient media. Absolute increments were greater in blast cells from patients with acute lymphoblastic leukemia and with acute myeloblastic leukemia than in lymphocytes from patients with chronic lymphocytic leukemia, but per cent increments did not differ. Time-related increases appear to be restricted to an active mechanism for AIB entry and could not be attributed to cell damage, concomitant alterations in the incubation media, or progressive reduction in transinhibition of AIB entry. Studies with two cell populations revealed these increases to be associated with an augmented Vmax and a reduction in apparent Km, suggesting enhanced capacity and affinity of the transport system for AIB. Time-related increases failed to develop in two chronic lymphocytic leukemia (CLL) lymphocyte populations and were partially reduced in two leukemic blast cell populations during continuous exposure to high extracellular AIB concentrations. Hence, this phenomenon may represent an adaptive response to environmental amino acid deprivation. Adaptation may involve de novo protein and RNA synthesis, since it was not seen in cells which were treated with cycloheximide or actinomycin D. However, unlike previous observations in nonmalignant cells, once triggered, the adaptive response was not completely suppressed in leukemic cells which underwent a large degree of adaptation.", "contents": "Adaptive enhancement of amino acid transport in human leukemia leukocytes: studies with alpha-aminoisobutyric acid. Initial rates of accumulation (Vi) of [3-14C] alpha-aminoisobutyric acid (AIB) by human leukemic leukocytes increased markedly and progressively during 240 minute incubations in amino acid-deficient media. Absolute increments were greater in blast cells from patients with acute lymphoblastic leukemia and with acute myeloblastic leukemia than in lymphocytes from patients with chronic lymphocytic leukemia, but per cent increments did not differ. Time-related increases appear to be restricted to an active mechanism for AIB entry and could not be attributed to cell damage, concomitant alterations in the incubation media, or progressive reduction in transinhibition of AIB entry. Studies with two cell populations revealed these increases to be associated with an augmented Vmax and a reduction in apparent Km, suggesting enhanced capacity and affinity of the transport system for AIB. Time-related increases failed to develop in two chronic lymphocytic leukemia (CLL) lymphocyte populations and were partially reduced in two leukemic blast cell populations during continuous exposure to high extracellular AIB concentrations. Hence, this phenomenon may represent an adaptive response to environmental amino acid deprivation. Adaptation may involve de novo protein and RNA synthesis, since it was not seen in cells which were treated with cycloheximide or actinomycin D. However, unlike previous observations in nonmalignant cells, once triggered, the adaptive response was not completely suppressed in leukemic cells which underwent a large degree of adaptation."} {"id": "PMID:172570", "title": "Glomus jugulare tumours. (A series of 21 cases).", "content": "Twenty-one cases of glomus jugulare tumours were analysed in retrospect. Six had been treated surgically, ten by irradiation, and five by a combination of incomplete surgical excision followed by irradiation. Recurrences appeared in four cases, but no patient has died of the tumour during the follow-up period which is from a few months to eleven years. Metastases were not found in any case. The optimal time of irradiation in combined treatment is discussed.", "contents": "Glomus jugulare tumours. (A series of 21 cases). Twenty-one cases of glomus jugulare tumours were analysed in retrospect. Six had been treated surgically, ten by irradiation, and five by a combination of incomplete surgical excision followed by irradiation. Recurrences appeared in four cases, but no patient has died of the tumour during the follow-up period which is from a few months to eleven years. Metastases were not found in any case. The optimal time of irradiation in combined treatment is discussed."} {"id": "PMID:172571", "title": "Rhabdomyoma purum of the larynx.", "content": "A case of pure well-differentiated rhabdomyoma of the larynx occurring in a 50-year-old male is reported. The lesion was localized to the interarytenoid region. From an accurate revision of the world literature on the subject it appears that the cases so far described number only seven, including the one in the present report. Furthermore, the differential histological and histochemical criteria for distinguishing rhabdomyoma from granular cell Schwannoma are discussed and tabulated, as the two neoplasms may be easily confused. In our case, there has been no evidence of recurrence of the tumour for more than 1 year, which is in accordance with the previous cases reported in the literature.", "contents": "Rhabdomyoma purum of the larynx. A case of pure well-differentiated rhabdomyoma of the larynx occurring in a 50-year-old male is reported. The lesion was localized to the interarytenoid region. From an accurate revision of the world literature on the subject it appears that the cases so far described number only seven, including the one in the present report. Furthermore, the differential histological and histochemical criteria for distinguishing rhabdomyoma from granular cell Schwannoma are discussed and tabulated, as the two neoplasms may be easily confused. In our case, there has been no evidence of recurrence of the tumour for more than 1 year, which is in accordance with the previous cases reported in the literature."} {"id": "PMID:172572", "title": "Hyperbaric oxygen in anaerobic infection of the medistinum.", "content": "In the last decade hyperbaric oxygen has been recognized as an important therapeutic tool in a variety of instances in which either destruction of anaerobic bacteria is urgent or an improvement in the oxygenation level is mandatory. We have used it successfully in a case of mediastinal anaerobic infection (gas gangrene) after medical and surgical measures had failed to eradicate the disease. The causative organism of gas gangrene, Clostridium perfringens (Welchii), is widely distributed. It may be cultured from the soil, house dust, human skin and faeces, etc. For this reason infection with Clostridium is practically inevitable whenever suitable conditions arise. As an anaerobic bacterium Clostridium Welchii multiplies readily in damaged tissues without contact with the air and devoid of a normal blood supply. This occurs especially in road accidents and war wounds in which broken bones and crushed muscles provide a suitable medium for the infection (Altmeier, 1965). Sometimes this infection can occur too after abdominal or gynaecological operations (Hitchcock, 1965). We present here a case of mediastinal gas gangrene which was caused by perforation of the oesophagus by a swallowed foreign body.", "contents": "Hyperbaric oxygen in anaerobic infection of the medistinum. In the last decade hyperbaric oxygen has been recognized as an important therapeutic tool in a variety of instances in which either destruction of anaerobic bacteria is urgent or an improvement in the oxygenation level is mandatory. We have used it successfully in a case of mediastinal anaerobic infection (gas gangrene) after medical and surgical measures had failed to eradicate the disease. The causative organism of gas gangrene, Clostridium perfringens (Welchii), is widely distributed. It may be cultured from the soil, house dust, human skin and faeces, etc. For this reason infection with Clostridium is practically inevitable whenever suitable conditions arise. As an anaerobic bacterium Clostridium Welchii multiplies readily in damaged tissues without contact with the air and devoid of a normal blood supply. This occurs especially in road accidents and war wounds in which broken bones and crushed muscles provide a suitable medium for the infection (Altmeier, 1965). Sometimes this infection can occur too after abdominal or gynaecological operations (Hitchcock, 1965). We present here a case of mediastinal gas gangrene which was caused by perforation of the oesophagus by a swallowed foreign body."} {"id": "PMID:172573", "title": "Role of lamellar inclusions in surfactant production: studies on phospholipid composition and biosynthesis in rat and rabbit lung subcellular fractions.", "content": "Lamellar inclusion bodies in the type II alveolar epithelial cell are believed to be involved in pulmonary surfactant production. However, it is not clear whether their role is that of synthesis, storage, or secretion. We have examined the phospholipid composition and fatty acid content of rabbit lung wash, lamellar bodies, mitochondria, and microsomes. Phosphatidylcholine and phosphatidylglycerol, the surface-active components of pulmonary surfactant, accounted for over 80% of the total phospholipid in lung wash and lamellar bodies but for only about 50% in mitochondria and microsomes. Phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin accounted for over 40% of the total in mitochondria and microsomes but for only 6% in lung wash and 15% in lamellar bodies. The fatty acid composition of lamellar body phosphatidylcholine was similar to that of lung wash, but different from that of mitochondria and microsomes, in containing palmitic acid as a major component with little stearic acid and few fatty acids of chain length greater than 18 carbon atoms. The biosynthesis of phosphatidylcholine and phosphatidylglycerol was examined in the mitochondrial, microsomal, and lamellar body fractions from rat lung. Cholinephosphotransferase was largely microsomal. The activity in the lamellar body fraction could be attributed to microsomal contamination. The activity of glycerolphosphate phosphatidyltransferase, however, was high in the lamellar body fraction, although it was highest in the mitochondria and was also active in the microsomes. These data suggest that the lamellar bodies are involved both in the storage of the lipid components of surfactant and in the synthesis of at least one of those components, phosphatidylglycerol.", "contents": "Role of lamellar inclusions in surfactant production: studies on phospholipid composition and biosynthesis in rat and rabbit lung subcellular fractions. Lamellar inclusion bodies in the type II alveolar epithelial cell are believed to be involved in pulmonary surfactant production. However, it is not clear whether their role is that of synthesis, storage, or secretion. We have examined the phospholipid composition and fatty acid content of rabbit lung wash, lamellar bodies, mitochondria, and microsomes. Phosphatidylcholine and phosphatidylglycerol, the surface-active components of pulmonary surfactant, accounted for over 80% of the total phospholipid in lung wash and lamellar bodies but for only about 50% in mitochondria and microsomes. Phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin accounted for over 40% of the total in mitochondria and microsomes but for only 6% in lung wash and 15% in lamellar bodies. The fatty acid composition of lamellar body phosphatidylcholine was similar to that of lung wash, but different from that of mitochondria and microsomes, in containing palmitic acid as a major component with little stearic acid and few fatty acids of chain length greater than 18 carbon atoms. The biosynthesis of phosphatidylcholine and phosphatidylglycerol was examined in the mitochondrial, microsomal, and lamellar body fractions from rat lung. Cholinephosphotransferase was largely microsomal. The activity in the lamellar body fraction could be attributed to microsomal contamination. The activity of glycerolphosphate phosphatidyltransferase, however, was high in the lamellar body fraction, although it was highest in the mitochondria and was also active in the microsomes. These data suggest that the lamellar bodies are involved both in the storage of the lipid components of surfactant and in the synthesis of at least one of those components, phosphatidylglycerol."} {"id": "PMID:172574", "title": "High-pressure liquid chromatography: separation of the metabolites of vitamins D2 and D3 on small-particle silica columns.", "content": "The high-pressure liquid chromatographic separation of all of the known metabolites of vitamin D(2) and vitamin D(3) found in biological fluids has been achieved. This technique has been successfully applied to the analysis of vitamin D mixtures, purification of vitamin D metabolites, and identification of radioactive peaks. Some theoretical bases for the observed resolutions are suggested.", "contents": "High-pressure liquid chromatography: separation of the metabolites of vitamins D2 and D3 on small-particle silica columns. The high-pressure liquid chromatographic separation of all of the known metabolites of vitamin D(2) and vitamin D(3) found in biological fluids has been achieved. This technique has been successfully applied to the analysis of vitamin D mixtures, purification of vitamin D metabolites, and identification of radioactive peaks. Some theoretical bases for the observed resolutions are suggested."} {"id": "PMID:172575", "title": "Determination of B protein of low density lipoprotein directly in plasma.", "content": "Quantitation of the apoprotein constituents of lipoproteins has extended our knowledge of plasma lipid transport. Previously, B protein content of low density lipoprotein could be measured by radial immunodiffusion only after ultracentrifugation. However, if performed in 1.5% agarose gel with standards and measured at 18 hr rather than at equilibrium, low density lipoprotein B protein can be measured directly in plasma, eliminating the need to separate very low density lipoprotein.", "contents": "Determination of B protein of low density lipoprotein directly in plasma. Quantitation of the apoprotein constituents of lipoproteins has extended our knowledge of plasma lipid transport. Previously, B protein content of low density lipoprotein could be measured by radial immunodiffusion only after ultracentrifugation. However, if performed in 1.5% agarose gel with standards and measured at 18 hr rather than at equilibrium, low density lipoprotein B protein can be measured directly in plasma, eliminating the need to separate very low density lipoprotein."} {"id": "PMID:172576", "title": "Radioiodinated lipoproteins: absorption of 125I radioactivity by high density solutions.", "content": "Concentrations of potassium bromide commonly used for separation of lipoproteins were shown to cause absorption of 125I and thus reduce the counting efficiency of the labeled lipoproteins. Chloroform was shown to cause a 50% reduction in counting efficiency of lipid from 125I-labeled lipoprotein. No reduction of counting efficiency was observed in the presence of high density solutions when 131I was used as label.", "contents": "Radioiodinated lipoproteins: absorption of 125I radioactivity by high density solutions. Concentrations of potassium bromide commonly used for separation of lipoproteins were shown to cause absorption of 125I and thus reduce the counting efficiency of the labeled lipoproteins. Chloroform was shown to cause a 50% reduction in counting efficiency of lipid from 125I-labeled lipoprotein. No reduction of counting efficiency was observed in the presence of high density solutions when 131I was used as label."} {"id": "PMID:172577", "title": "Modification of myometrial activity in vivo by administration of cyclic nucleotides and theophylline to the pregnant rat.", "content": "Myometrial activity was recorded in vivo in unrestrained pregnant rats from day 19 of gestation using radiotelemetry. The effects of short-term infusions of theophylline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were investigated. All three compounds caused a decrease in oxytocin-induced, prostaglandin F2alpha-induced and spontaneous uterine activity. After cessation of the infusion of these compounds uterine activity returned to near pre-infusion levels within approximately 15 min in most animals. The possible roles of cyclic nucleotides in the control of myometrial contraction are discussed in the light of these observations.", "contents": "Modification of myometrial activity in vivo by administration of cyclic nucleotides and theophylline to the pregnant rat. Myometrial activity was recorded in vivo in unrestrained pregnant rats from day 19 of gestation using radiotelemetry. The effects of short-term infusions of theophylline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were investigated. All three compounds caused a decrease in oxytocin-induced, prostaglandin F2alpha-induced and spontaneous uterine activity. After cessation of the infusion of these compounds uterine activity returned to near pre-infusion levels within approximately 15 min in most animals. The possible roles of cyclic nucleotides in the control of myometrial contraction are discussed in the light of these observations."} {"id": "PMID:172578", "title": "Comparison of the characteristics and of the hormonal control of endometrial and myometrial progesterone receptors.", "content": "The characteristics of endometrial and myometrial progesterone receptor of guinea-pig were compared. Affinity for progesterone, hormone specificity, sedimentation properties (in oestrogen-primed animals), inhibition of binding by p-hydroxymercuribenzoate were found to be identical in both tissue. Differences were, however, observed in the hormonal control of the concentration of receptor. In all the situations studied, the concentration of receptors was higher in the endometrium than in the myometrium. In guinea-pigs ovariectomized at dioestrus the concentration was 3500 binding sites per diploid genome in the myometrium and 20300 in the endometrium; 1-3 days after oestradiol injection, this concentration was raised to 46000-38000 and 65000-83000 binding sites respectively. Thus the absolute rise was similar in both tissues but the relative increase was about 15-fold in the myometrium and only three- to fourfold in the endometrium. After injection of 2 mg progesterone, the concentration of receptor previously induced by oestrogen returned to very low values similar to those observed in non-hormonally treated controls. This difference between endometrial and myometrial receptors could be due either to a faster turnover of the latter or to the existence of a stable non-hormonally controlled population of receptors, present only in the endometrium.", "contents": "Comparison of the characteristics and of the hormonal control of endometrial and myometrial progesterone receptors. The characteristics of endometrial and myometrial progesterone receptor of guinea-pig were compared. Affinity for progesterone, hormone specificity, sedimentation properties (in oestrogen-primed animals), inhibition of binding by p-hydroxymercuribenzoate were found to be identical in both tissue. Differences were, however, observed in the hormonal control of the concentration of receptor. In all the situations studied, the concentration of receptors was higher in the endometrium than in the myometrium. In guinea-pigs ovariectomized at dioestrus the concentration was 3500 binding sites per diploid genome in the myometrium and 20300 in the endometrium; 1-3 days after oestradiol injection, this concentration was raised to 46000-38000 and 65000-83000 binding sites respectively. Thus the absolute rise was similar in both tissues but the relative increase was about 15-fold in the myometrium and only three- to fourfold in the endometrium. After injection of 2 mg progesterone, the concentration of receptor previously induced by oestrogen returned to very low values similar to those observed in non-hormonally treated controls. This difference between endometrial and myometrial receptors could be due either to a faster turnover of the latter or to the existence of a stable non-hormonally controlled population of receptors, present only in the endometrium."} {"id": "PMID:172579", "title": "Effect of magnesium deficiency and parathyroid hormone on cyclic AMP metabolism in rat renal cortex.", "content": "The influence of magnesium deficiency on cyclic AMP metabolism was investigated in rats on diets of normal and low calcium content. Magnesium deficiency itself did not significantly affect either the basal concentration or the parathyroid hormone-stimulated formation of cyclic AMP in the renal cortex. Magnesium-deficient rats with hypercalcaemia excreted more cyclic AMP in the urine, but similar rats that developed hypocalcaemia on low calcium intake excreted less than their respective controls. The former type of animals also tended to accumulate more cyclic AMP in the renal cortex in response to the injection of a standard dose of parathyroid hormone, whereas rats of the latter type accumulated less. The activity of parathyroid hormone-stimulated renal cortical adenylate cyclase in vitro was increased by magnesium and reduced by calcium under most conditions, but with low concentrations of magnesium small amounts of calcium had a stimulatory effect. These observations suggest that cyclic AMP metabolism is influenced by metabolic disorders developing secondary to magnesium deficiency.", "contents": "Effect of magnesium deficiency and parathyroid hormone on cyclic AMP metabolism in rat renal cortex. The influence of magnesium deficiency on cyclic AMP metabolism was investigated in rats on diets of normal and low calcium content. Magnesium deficiency itself did not significantly affect either the basal concentration or the parathyroid hormone-stimulated formation of cyclic AMP in the renal cortex. Magnesium-deficient rats with hypercalcaemia excreted more cyclic AMP in the urine, but similar rats that developed hypocalcaemia on low calcium intake excreted less than their respective controls. The former type of animals also tended to accumulate more cyclic AMP in the renal cortex in response to the injection of a standard dose of parathyroid hormone, whereas rats of the latter type accumulated less. The activity of parathyroid hormone-stimulated renal cortical adenylate cyclase in vitro was increased by magnesium and reduced by calcium under most conditions, but with low concentrations of magnesium small amounts of calcium had a stimulatory effect. These observations suggest that cyclic AMP metabolism is influenced by metabolic disorders developing secondary to magnesium deficiency."} {"id": "PMID:172580", "title": "Osmotic inhibition of the natriferic response of the toad urinary bladder to vasopressin.", "content": "The electrical potential difference and short-circuit current (scc, reflecting active transmural sodium transport) across the toad urinary bladder in vitro was unaffected by the presence of hypo-osmotic solutions bathing the mucosal (urinary) surface, providing that the transmural flow of water was small. Vasopressin increased the scc across the toad bladder (the natriferic response), but this stimulation was considerably reduced in the presence of a hypo-osmotic solution on the mucosal side, conditions under which water transfer across the membrane was also increased. This inhibition of the natriferic response did not depend on the direction of the water movement, for if the osmotic gradient was the opposite way to that which normally occurs, the response to vasopressin was still reduced. The natriferic response to cyclic AMP was also inhibited in the presence of an osmotic gradient. Aldosterone increased the scc and Na+ transport across the toad bladder but this response was not changed when an osmotic gradient was present. The physiological implications of these observations and the possible mechanisms involved are discussed.", "contents": "Osmotic inhibition of the natriferic response of the toad urinary bladder to vasopressin. The electrical potential difference and short-circuit current (scc, reflecting active transmural sodium transport) across the toad urinary bladder in vitro was unaffected by the presence of hypo-osmotic solutions bathing the mucosal (urinary) surface, providing that the transmural flow of water was small. Vasopressin increased the scc across the toad bladder (the natriferic response), but this stimulation was considerably reduced in the presence of a hypo-osmotic solution on the mucosal side, conditions under which water transfer across the membrane was also increased. This inhibition of the natriferic response did not depend on the direction of the water movement, for if the osmotic gradient was the opposite way to that which normally occurs, the response to vasopressin was still reduced. The natriferic response to cyclic AMP was also inhibited in the presence of an osmotic gradient. Aldosterone increased the scc and Na+ transport across the toad bladder but this response was not changed when an osmotic gradient was present. The physiological implications of these observations and the possible mechanisms involved are discussed."} {"id": "PMID:172582", "title": "Levels of corticotrophin analogues in the blood after infusion into rats.", "content": "An isolated rat adrenal cell bioassay was used to measure blood concentrations in rats after infusion of synthetic human ACTH, corticotrophin-(1-24)-tetracosapeptide or [D-Ser1, Lys17, Lys18]corticotrophin-(1-18)-octadecapeptide amide. Lower blood levels were found with the 1-24 peptide than with human ACTH and the highest levels were found with the 1-18 peptide. These results suggest that the 1-24 peptide which is almost equipotent with natural ACTH in vivo may be more potent at the receptor and corroborate findings to this effect obtained with isolated adrenal cells. The high potency and prolonged action of the 1-18 analogue in vivo are also explained by these results. Low arterial blood concentrations of the 1-24 peptide and human ACTH were found during infusion, suggesting that substantial inactivation must be occurring in a single passage through the lungs. The effects of renal ligature on blood concentrations indicated that the kidney is involved in handling the 1-18 peptide and that human ACTH is also cleared by this organ. After infusion the fall in blood concentrations was biphasic. It is suggested that the rapid phase is due to clearance of peptides in the circulation which results in a fall to lower blood concentrations which are sustained by slow release of peptide from binding sites which act as a depot.", "contents": "Levels of corticotrophin analogues in the blood after infusion into rats. An isolated rat adrenal cell bioassay was used to measure blood concentrations in rats after infusion of synthetic human ACTH, corticotrophin-(1-24)-tetracosapeptide or [D-Ser1, Lys17, Lys18]corticotrophin-(1-18)-octadecapeptide amide. Lower blood levels were found with the 1-24 peptide than with human ACTH and the highest levels were found with the 1-18 peptide. These results suggest that the 1-24 peptide which is almost equipotent with natural ACTH in vivo may be more potent at the receptor and corroborate findings to this effect obtained with isolated adrenal cells. The high potency and prolonged action of the 1-18 analogue in vivo are also explained by these results. Low arterial blood concentrations of the 1-24 peptide and human ACTH were found during infusion, suggesting that substantial inactivation must be occurring in a single passage through the lungs. The effects of renal ligature on blood concentrations indicated that the kidney is involved in handling the 1-18 peptide and that human ACTH is also cleared by this organ. After infusion the fall in blood concentrations was biphasic. It is suggested that the rapid phase is due to clearance of peptides in the circulation which results in a fall to lower blood concentrations which are sustained by slow release of peptide from binding sites which act as a depot."} {"id": "PMID:172583", "title": "[Neurulation and interkinetic nuclear migration in the chick embryo (author's transl)].", "content": "Neurulation and interkinetic nuclear migration was studied in cells of the forming neural tube of chick embryos submitted to a variety of treatments. Our results show that cytochalasin B (5 mug/ml) does not protect microtubules against disruption occurring after 3 h at 2 degrees C nor does it prevent their repolymerization once they are cold-disrupted. However, db-cAMP protects microtubules against such cold disruption. We indicate that the inhibitory effect of cytochalasin B on interkinetic nuclear migration cannot be ascribed to an effect on microtubules.", "contents": "[Neurulation and interkinetic nuclear migration in the chick embryo (author's transl)]. Neurulation and interkinetic nuclear migration was studied in cells of the forming neural tube of chick embryos submitted to a variety of treatments. Our results show that cytochalasin B (5 mug/ml) does not protect microtubules against disruption occurring after 3 h at 2 degrees C nor does it prevent their repolymerization once they are cold-disrupted. However, db-cAMP protects microtubules against such cold disruption. We indicate that the inhibitory effect of cytochalasin B on interkinetic nuclear migration cannot be ascribed to an effect on microtubules."} {"id": "PMID:172584", "title": "Effects of helium and other inert gases on Echinosphaerium nucleofilium (protozoa, heliozoa).", "content": "The effects of helium, nitrogen, argon and krypton on Echinosphaerium nucleofilum (Heliozoa) have been studied at partial pressures of 10-130 atm. Additional experiments have been carried out with hydrostatic pressure alone. Helium causes shortening of the axopods over the whole range of pressures, and damage to the cell body at pressures of 60-90 atm, both with a maximum at 80 atm. These effects cannot be explained in terms of hydrostatic pressure alone; a 'pressure reversal' effect may be operating, causing the peak at 80 atm. Nitrogen also causes both cell damage and axopod shortening, the severity increasing with increasing pressure. Argon and krypton cause cell damage but no shortening. The order of potency for cell damage is krypton greater than argon greater than nitrogen greater than helium. It is suggested that there may be tuo sites of action, possibly the microtubules (for axopod shortening) and the cell membrane (for cell damage). In appropriate mixtures of helium and argon, both the cell damage usually caused by argon, and the axopod shortening usually caused by helium, are prevented. Possible mechanisms include the effects of hydrostatic pressure on gas solubility coefficients, reversal of the effects of the gases by the increase in total pressure, and competition for sites of action.", "contents": "Effects of helium and other inert gases on Echinosphaerium nucleofilium (protozoa, heliozoa). The effects of helium, nitrogen, argon and krypton on Echinosphaerium nucleofilum (Heliozoa) have been studied at partial pressures of 10-130 atm. Additional experiments have been carried out with hydrostatic pressure alone. Helium causes shortening of the axopods over the whole range of pressures, and damage to the cell body at pressures of 60-90 atm, both with a maximum at 80 atm. These effects cannot be explained in terms of hydrostatic pressure alone; a 'pressure reversal' effect may be operating, causing the peak at 80 atm. Nitrogen also causes both cell damage and axopod shortening, the severity increasing with increasing pressure. Argon and krypton cause cell damage but no shortening. The order of potency for cell damage is krypton greater than argon greater than nitrogen greater than helium. It is suggested that there may be tuo sites of action, possibly the microtubules (for axopod shortening) and the cell membrane (for cell damage). In appropriate mixtures of helium and argon, both the cell damage usually caused by argon, and the axopod shortening usually caused by helium, are prevented. Possible mechanisms include the effects of hydrostatic pressure on gas solubility coefficients, reversal of the effects of the gases by the increase in total pressure, and competition for sites of action."} {"id": "PMID:172585", "title": "Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein.", "content": "Rosette inhibitory factor, RIF, previously described in serum from patients with hepatitis B virus infection, has been isolated and identified as a minor species of beta-lipoprotein of the low-density (LDL) class. It is unrelated to hepatitis B virus proteins or particles. Although discrete by reference to charge and density (1.050 +/- 0.004 g/cm3), RIF appears to be a complex macromolecular structure containing apolipoproteins A, B, and C. Greater than 400% recovery is achieved upon 300,000-fold purification from RIF+ sera suggesting activation of a precursor form that is not present in normal serum. RIF inhibits E rosette function of T lymphocytes in vitro with a lag period of approximately 4 h and maximal effect at 24 h consistent with a metabolically-induced event. RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. Approximately 2,900 receptors for RIF appear to be present per cell and a high mutual affinity is apparent (k approximately to 9 X 10(10) liters/mol). RIF has no detectable effect on mitogen (PHA) responsiveness of lymphocytes, but inhibits the capacity of lymphocytes to respond to histoincompatible cells in vitro at concentrations greater than 10(-8) M. Equivalent RIF- lipoprotein fractions from normal serum are equally inhibitory in the mixed lymphocyte reaction suggesting that this effect is not directly attributable to RIF activity. These data indicate that RIF is a unique and functionally specific species of LDL that represents either an association complex of lipoproteins or a hybrid molecule of unusual composition. The association of this factor with viral-induced hepatocellular injury underscores the need to elucidate its structure and function in greater detail.", "contents": "Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein. Rosette inhibitory factor, RIF, previously described in serum from patients with hepatitis B virus infection, has been isolated and identified as a minor species of beta-lipoprotein of the low-density (LDL) class. It is unrelated to hepatitis B virus proteins or particles. Although discrete by reference to charge and density (1.050 +/- 0.004 g/cm3), RIF appears to be a complex macromolecular structure containing apolipoproteins A, B, and C. Greater than 400% recovery is achieved upon 300,000-fold purification from RIF+ sera suggesting activation of a precursor form that is not present in normal serum. RIF inhibits E rosette function of T lymphocytes in vitro with a lag period of approximately 4 h and maximal effect at 24 h consistent with a metabolically-induced event. RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. Approximately 2,900 receptors for RIF appear to be present per cell and a high mutual affinity is apparent (k approximately to 9 X 10(10) liters/mol). RIF has no detectable effect on mitogen (PHA) responsiveness of lymphocytes, but inhibits the capacity of lymphocytes to respond to histoincompatible cells in vitro at concentrations greater than 10(-8) M. Equivalent RIF- lipoprotein fractions from normal serum are equally inhibitory in the mixed lymphocyte reaction suggesting that this effect is not directly attributable to RIF activity. These data indicate that RIF is a unique and functionally specific species of LDL that represents either an association complex of lipoproteins or a hybrid molecule of unusual composition. The association of this factor with viral-induced hepatocellular injury underscores the need to elucidate its structure and function in greater detail."} {"id": "PMID:172586", "title": "Endogenous oncornaviral gene expression in adult and fetal mice: quantitative, histologic, and physiologic studies of the major viral glycorprotein, gp70.", "content": "Endogenous expression of the murine leukemia virus (MuLV) genome has been studied in a number of strains of mice. Expression of the major envelope glycoprotein, gp70, is restricted to certain anatomical sites and cell types, prominent among which are lymphoid and epithelial cells. On a quantitative basis, the major site of gp70 expression is the male genital tract. During development, gp70 first appears in the hematopoietic liver of 14-day-old embryos and by day 18, it is already expressed at anatomical sites similar to those of the adult. In toto, these results show that control of expression of the MuLV genome in adult and developing mice is linked to differentiation.", "contents": "Endogenous oncornaviral gene expression in adult and fetal mice: quantitative, histologic, and physiologic studies of the major viral glycorprotein, gp70. Endogenous expression of the murine leukemia virus (MuLV) genome has been studied in a number of strains of mice. Expression of the major envelope glycoprotein, gp70, is restricted to certain anatomical sites and cell types, prominent among which are lymphoid and epithelial cells. On a quantitative basis, the major site of gp70 expression is the male genital tract. During development, gp70 first appears in the hematopoietic liver of 14-day-old embryos and by day 18, it is already expressed at anatomical sites similar to those of the adult. In toto, these results show that control of expression of the MuLV genome in adult and developing mice is linked to differentiation."} {"id": "PMID:172587", "title": "Relationship of infectious murine leukemia virus and virus-related antigens in genetic crosses between AKR and the Fv-1 compatible strain C57L.", "content": "In a further genetic study of murine leukemia virus (MuLV) and its components we examined the backcross C57L X (C57L X AKR). This population was selected because strains AKR and C57L are both Fv-1n, and the restriction which the Fu-1b allele imposes on the output of virus was thereby obviated. The segregants were scored for three characters: (a) infectious Gross-AKR-type MuLV (V), in the tail; (b) group-specific antigen indicative of p30 internal viral protein, in spleen; and (c) GIX antigen, now thought to be indicative of gp69/71 viral envelope glycoprotein, on thymocytes. Our conclusions are: (a) It is confirmed that the AKR mouse has two unlinked chromosomal genes, Akv-1 and Akv-2, each of which can independently give rise to the life-long high output of MuLV that is characteristic of AKR mice. (b) Of the eight phenotypes that could possibly be derived from segregation of the three pairs of independent alternative traits, seven were observed, but on progeny testing only three were shown to reflect stably heritable genotypes; these were V+p30+GIX+ and V-p30-GIX- (the parental types) and V-p30+GIX+. A third, newly identified AKR gene, designated Akvp, segregating independently of Akv-1 and Akv-2, also determines expression of p30 and GIX but in this case independently of XC-detectable MuLV. (c) The four remaining observed phenotypes, which did not breed true on progeny testing, involved mostly antigen-negative parents yielding antigen-positive progeny; it is likely that these discrepancies represented suppression of phenotype by a maternal resistance factor.", "contents": "Relationship of infectious murine leukemia virus and virus-related antigens in genetic crosses between AKR and the Fv-1 compatible strain C57L. In a further genetic study of murine leukemia virus (MuLV) and its components we examined the backcross C57L X (C57L X AKR). This population was selected because strains AKR and C57L are both Fv-1n, and the restriction which the Fu-1b allele imposes on the output of virus was thereby obviated. The segregants were scored for three characters: (a) infectious Gross-AKR-type MuLV (V), in the tail; (b) group-specific antigen indicative of p30 internal viral protein, in spleen; and (c) GIX antigen, now thought to be indicative of gp69/71 viral envelope glycoprotein, on thymocytes. Our conclusions are: (a) It is confirmed that the AKR mouse has two unlinked chromosomal genes, Akv-1 and Akv-2, each of which can independently give rise to the life-long high output of MuLV that is characteristic of AKR mice. (b) Of the eight phenotypes that could possibly be derived from segregation of the three pairs of independent alternative traits, seven were observed, but on progeny testing only three were shown to reflect stably heritable genotypes; these were V+p30+GIX+ and V-p30-GIX- (the parental types) and V-p30+GIX+. A third, newly identified AKR gene, designated Akvp, segregating independently of Akv-1 and Akv-2, also determines expression of p30 and GIX but in this case independently of XC-detectable MuLV. (c) The four remaining observed phenotypes, which did not breed true on progeny testing, involved mostly antigen-negative parents yielding antigen-positive progeny; it is likely that these discrepancies represented suppression of phenotype by a maternal resistance factor."} {"id": "PMID:172588", "title": "Comparative studies of purinergic nerves.", "content": "Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in \"receptive relaxation\" of the stomach, \"descending inhibition\" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of \"large opaque vesicles,\" which can be distinguished from the \"large granular vesicles\" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The \"rebound contraction\" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type.", "contents": "Comparative studies of purinergic nerves. Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in \"receptive relaxation\" of the stomach, \"descending inhibition\" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of \"large opaque vesicles,\" which can be distinguished from the \"large granular vesicles\" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The \"rebound contraction\" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type."} {"id": "PMID:172589", "title": "Comparative physiology and the challenge of design.", "content": "Analysis of the complexity of biological organization commonly takes us through an initial and necessary stage of over-simplification towards the ultimate goal of an appreciation of the subtle intricacy of nature. One example of this is that recent advances in studies of the phosphagens have failed to confirm earlier hopes that the distribution of these substances could be used to confirm phylogenetic relationships. It is now suggested that a previously unrecognized factor influencing this distribution may be competing demands for arginine in the development of the testes. Another illustration is the belief that the presence of iodine in ascidians may provide a clue to the origin of thyroidal biosynthesis. This belief is probably sound, but the presence of abundant iodine in the tunic may well be a false trail. More significant is the presence of much smaller amounts of bound iodine in the endostyle, where its presence is probably correlated with specialized protein metabolism associated with the ciliary feeding mechanism. A third illustration, discussed in more detail, is provided by recent recognition that the gut is a major component of the vertebrate endocrine system. This lays open attractive fields of research, ranging from problems of molecular and hormonal evolution to aspects of fish farming and the physiology of gut parasites. The need is thus plain for breadth of perspective in comparative physiological research, and for recognition that the ultimate concern of the biologist is with the life and relationships of the whole organism.", "contents": "Comparative physiology and the challenge of design. Analysis of the complexity of biological organization commonly takes us through an initial and necessary stage of over-simplification towards the ultimate goal of an appreciation of the subtle intricacy of nature. One example of this is that recent advances in studies of the phosphagens have failed to confirm earlier hopes that the distribution of these substances could be used to confirm phylogenetic relationships. It is now suggested that a previously unrecognized factor influencing this distribution may be competing demands for arginine in the development of the testes. Another illustration is the belief that the presence of iodine in ascidians may provide a clue to the origin of thyroidal biosynthesis. This belief is probably sound, but the presence of abundant iodine in the tunic may well be a false trail. More significant is the presence of much smaller amounts of bound iodine in the endostyle, where its presence is probably correlated with specialized protein metabolism associated with the ciliary feeding mechanism. A third illustration, discussed in more detail, is provided by recent recognition that the gut is a major component of the vertebrate endocrine system. This lays open attractive fields of research, ranging from problems of molecular and hormonal evolution to aspects of fish farming and the physiology of gut parasites. The need is thus plain for breadth of perspective in comparative physiological research, and for recognition that the ultimate concern of the biologist is with the life and relationships of the whole organism."} {"id": "PMID:172590", "title": "Failure of gonadotropins to induce in vitro maturation of mouse oocytes treated with dibutyryl cyclic AMP.", "content": "In sufficient concentration, dibutyryl cAMP (DBC) prevents the spontaneous in vitro maturation of mouse oocytes. The effects of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on this inhibition were tested in an oil-free chamber-slide culture system. Mouse oocytes devoid of cumulus cells were incubated in the presence of DBC and/or gonadotropins. Oocytes cultured with follicle cells were similarly treated. Whether follicle cells were present or absent, DBC (100 or 500 mug/ml) prevented germinal vesicle breakdown in more than 95% of the oocytes cultured. Neither LH nor FSH in a wide range of concentrations acted directly on the oocytes or indirectly through the follicle cells to initiate maturation in oocytes incubated with 100 mug DBC/ml. The combination of LH (5 mug/ml) and FSH (10 mug/ml) was also ineffective in overcoming the block induced by either 100 or 50 mug DBC/ml. Maturation of oocytes in each of the DBC-free LH or FSH treatments was comparable to that occurring in control medium which did not contain exogenous gonadotropins or DBC. It was concluded that cultured oocytes treated with DBC are not a satisfactory model for studying the steps by which gonadotropins trigger the resumption of meiosis in mammalian oocytes.", "contents": "Failure of gonadotropins to induce in vitro maturation of mouse oocytes treated with dibutyryl cyclic AMP. In sufficient concentration, dibutyryl cAMP (DBC) prevents the spontaneous in vitro maturation of mouse oocytes. The effects of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on this inhibition were tested in an oil-free chamber-slide culture system. Mouse oocytes devoid of cumulus cells were incubated in the presence of DBC and/or gonadotropins. Oocytes cultured with follicle cells were similarly treated. Whether follicle cells were present or absent, DBC (100 or 500 mug/ml) prevented germinal vesicle breakdown in more than 95% of the oocytes cultured. Neither LH nor FSH in a wide range of concentrations acted directly on the oocytes or indirectly through the follicle cells to initiate maturation in oocytes incubated with 100 mug DBC/ml. The combination of LH (5 mug/ml) and FSH (10 mug/ml) was also ineffective in overcoming the block induced by either 100 or 50 mug DBC/ml. Maturation of oocytes in each of the DBC-free LH or FSH treatments was comparable to that occurring in control medium which did not contain exogenous gonadotropins or DBC. It was concluded that cultured oocytes treated with DBC are not a satisfactory model for studying the steps by which gonadotropins trigger the resumption of meiosis in mammalian oocytes."} {"id": "PMID:172594", "title": "Mach bands in the lateral eye of Limulus.", "content": "Patterns of optic nerve activity were computed for stationary step patterns of illumination from theoretical models of lateral inhibiton based on revised Hartlin-Ratliff equations. The computed response patterns contain well-defined Mach bands which match closely in amplitude and shape those recorded from single optic nerve fibers of the Limulus lateral eye. Theory and experiment show that the amplitude of the Mach bands is reduced by in inhibitory nonlinearity, the width of the Mach bands is approximately equal to the lateral dimension of the inhibitory field, but the shapes of the Mach bands are poor indices of the precise configuration of the inhibitory field. Theorems are proved establishing the equivalence of Mach-band patterns for models of different dimensions and a uniqueness condition for solutions of the piecewise linear model.", "contents": "Mach bands in the lateral eye of Limulus. Patterns of optic nerve activity were computed for stationary step patterns of illumination from theoretical models of lateral inhibiton based on revised Hartlin-Ratliff equations. The computed response patterns contain well-defined Mach bands which match closely in amplitude and shape those recorded from single optic nerve fibers of the Limulus lateral eye. Theory and experiment show that the amplitude of the Mach bands is reduced by in inhibitory nonlinearity, the width of the Mach bands is approximately equal to the lateral dimension of the inhibitory field, but the shapes of the Mach bands are poor indices of the precise configuration of the inhibitory field. Theorems are proved establishing the equivalence of Mach-band patterns for models of different dimensions and a uniqueness condition for solutions of the piecewise linear model."} {"id": "PMID:172595", "title": "Sodium chloride transport by rabbit gallbladder. Direct evidence for a coupled NaCl influx process.", "content": "The results of the present study that NaCl transport by in vitro rabbit gallbladder must be a consequence of a neutral coupled carrier-mediated mechanism that ultimately results in the active absorption of both ions; pure electrical coupling between the movements of Na and Cl can be excluded on the grounds of electrphysiologic considerations. Studies on the unidirectional influxes of Na and Cl have localized the site of this coupled mechanism to the mucosal membranes. Studies on the intracellular ion concentrations and the intracellular electrical potential are consistent with the notion that (a) the coupled NaCl influx process results in the movement of Cl from the mucosal solution into the cell against an apparent electrochemical potential difference; (b) the energy for the uphill movement of Cl is derived from the Na gradient across the mucosal membrane which is maintained by an active Na extrusion mechanism located at the basolateral membranes; and (c) Cl exit from the cell across the basolateral membranes is directed down an electrochemical potential gradient and may be diffusional. Finally, as for the case of rabbit ileum, the coupled NaCl influx process is inhibited by elevated intracellular levels of cyclic 3',5'-adenosine monophosphate. A working model for transcellular and paracellular NaCl transport by in vitro rabbit gallbladder is proposed.", "contents": "Sodium chloride transport by rabbit gallbladder. Direct evidence for a coupled NaCl influx process. The results of the present study that NaCl transport by in vitro rabbit gallbladder must be a consequence of a neutral coupled carrier-mediated mechanism that ultimately results in the active absorption of both ions; pure electrical coupling between the movements of Na and Cl can be excluded on the grounds of electrphysiologic considerations. Studies on the unidirectional influxes of Na and Cl have localized the site of this coupled mechanism to the mucosal membranes. Studies on the intracellular ion concentrations and the intracellular electrical potential are consistent with the notion that (a) the coupled NaCl influx process results in the movement of Cl from the mucosal solution into the cell against an apparent electrochemical potential difference; (b) the energy for the uphill movement of Cl is derived from the Na gradient across the mucosal membrane which is maintained by an active Na extrusion mechanism located at the basolateral membranes; and (c) Cl exit from the cell across the basolateral membranes is directed down an electrochemical potential gradient and may be diffusional. Finally, as for the case of rabbit ileum, the coupled NaCl influx process is inhibited by elevated intracellular levels of cyclic 3',5'-adenosine monophosphate. A working model for transcellular and paracellular NaCl transport by in vitro rabbit gallbladder is proposed."} {"id": "PMID:172596", "title": "Human platelet secretion and aggregation induced by calcium ionophores. Inhibition by PGE1 and dibutyryl cyclic AMP.", "content": "Ca2+, Mg2+-ionophores X537A and A23,187 (10(-7)-10(-6) M) induced the release of adenine nucleotides adenosine diphosphate (ADP, adenosine triphosphate (ATP), serotonin, beta-glucuronidase, Ca2+, and Mg2+ from washed human platelets. Enzymes present in the cytoplasm or mitochondria, and Zn2+ were not released. The rate of ATP and Ca2+ release measured by firefly lantern extract and murexide dye, respectively, was equivalent to that produced by the physiological stimulant thrombin. Ionophore-induced release of ADP, and serotonin was substantially (approximately 60%) but not completely inhibited by EGTA, EDTA, and high extracellular Mg2+, without significant reduction of Ca2+ release. The ionophore-induced release reaction is therefore partly dependent upon uptake of extracellular Ca2+ (demonstrated using 45Ca), but also occurs to a significant extent due to release into the cytoplasm of intracellular Ca2+. The ionophore-induced release reaction and aggregation of platelets could be blocked by prostaglandin E1 (PGE1) or dibutyryl cyclic AMP. The effects of PGE1, and N6, O2-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (dibutyryl cAMP) were synergistically potentiated by the phosphodiesterase inhibitor theophylline. It is proposed that Ca2+ is the physiological trigger for platelet secretion and aggregation and that its intracellular effects are strongly modulated by adenosine 3':5'-cyclic monophosphoric acid (cyclic AMP).", "contents": "Human platelet secretion and aggregation induced by calcium ionophores. Inhibition by PGE1 and dibutyryl cyclic AMP. Ca2+, Mg2+-ionophores X537A and A23,187 (10(-7)-10(-6) M) induced the release of adenine nucleotides adenosine diphosphate (ADP, adenosine triphosphate (ATP), serotonin, beta-glucuronidase, Ca2+, and Mg2+ from washed human platelets. Enzymes present in the cytoplasm or mitochondria, and Zn2+ were not released. The rate of ATP and Ca2+ release measured by firefly lantern extract and murexide dye, respectively, was equivalent to that produced by the physiological stimulant thrombin. Ionophore-induced release of ADP, and serotonin was substantially (approximately 60%) but not completely inhibited by EGTA, EDTA, and high extracellular Mg2+, without significant reduction of Ca2+ release. The ionophore-induced release reaction is therefore partly dependent upon uptake of extracellular Ca2+ (demonstrated using 45Ca), but also occurs to a significant extent due to release into the cytoplasm of intracellular Ca2+. The ionophore-induced release reaction and aggregation of platelets could be blocked by prostaglandin E1 (PGE1) or dibutyryl cyclic AMP. The effects of PGE1, and N6, O2-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (dibutyryl cAMP) were synergistically potentiated by the phosphodiesterase inhibitor theophylline. It is proposed that Ca2+ is the physiological trigger for platelet secretion and aggregation and that its intracellular effects are strongly modulated by adenosine 3':5'-cyclic monophosphoric acid (cyclic AMP)."} {"id": "PMID:172597", "title": "Receiver operating characteristic analysis. Application to the study of quantum fluctuation effects in optic nerve of Rana pipiens.", "content": "Receiver operating characteristic (ROC) analysis of nerve messages is described. The hypothesis that quantum fluctuations provide the only limit to the ability of frog ganglion cells to signal luminance change information is examined using ROC analysis. In the context of ROC analysis, the quantum fluctuation hypothesis predicts (a) the detectability of a luminance change signal should rise proportionally to the size of the change, (b) detectability should decrease as the square root of background, an implication of which is the deVries-Rose law, and (c) ROC curves should exhibit a shape particular to underlying Poisson distributions. Each of these predictions is confirmed for the responses of dimming ganglion cells to brief luminance decrements at scotopic levels, but none could have been tested using classical nerve message analysis procedures.", "contents": "Receiver operating characteristic analysis. Application to the study of quantum fluctuation effects in optic nerve of Rana pipiens. Receiver operating characteristic (ROC) analysis of nerve messages is described. The hypothesis that quantum fluctuations provide the only limit to the ability of frog ganglion cells to signal luminance change information is examined using ROC analysis. In the context of ROC analysis, the quantum fluctuation hypothesis predicts (a) the detectability of a luminance change signal should rise proportionally to the size of the change, (b) detectability should decrease as the square root of background, an implication of which is the deVries-Rose law, and (c) ROC curves should exhibit a shape particular to underlying Poisson distributions. Each of these predictions is confirmed for the responses of dimming ganglion cells to brief luminance decrements at scotopic levels, but none could have been tested using classical nerve message analysis procedures."} {"id": "PMID:172598", "title": "The respiratory system of Chromobacterium violaceum grown under conditions of high and low cyanide evolution.", "content": "The particulate fraction of disrupted Chromobacterium violaceum grown under cyanide-evolving conditions was unable to oxidize ascorbate plus N,N,N',N'-tetra-methyl-p-phenylenediamine (TMPD), but oxidized NADH and succinate by a linear respiratory pathway which was very resistant to inhibition by cyanide. When the bacteria were grown under conditions where little cyanide evolution occurred, particulate fractions developed the ability to oxidize ascorbate-TMPD by a pathway highly sensitive to cyanide inhibition; respiratory activity with NADH and succinate proceeded via both the cyanide-sensitive and-resistant pathways. Studies with respiratory inhibitors, and the cytochrome compositions of the fractions derived from cultures grown under both conditions, are presented. A soluble, carbon monoxide-binding cytochrome c was found, and this appears similar to those found recently in Beneckea natiegens, methylotrophic bacteria and the marine pseudomonad B16.", "contents": "The respiratory system of Chromobacterium violaceum grown under conditions of high and low cyanide evolution. The particulate fraction of disrupted Chromobacterium violaceum grown under cyanide-evolving conditions was unable to oxidize ascorbate plus N,N,N',N'-tetra-methyl-p-phenylenediamine (TMPD), but oxidized NADH and succinate by a linear respiratory pathway which was very resistant to inhibition by cyanide. When the bacteria were grown under conditions where little cyanide evolution occurred, particulate fractions developed the ability to oxidize ascorbate-TMPD by a pathway highly sensitive to cyanide inhibition; respiratory activity with NADH and succinate proceeded via both the cyanide-sensitive and-resistant pathways. Studies with respiratory inhibitors, and the cytochrome compositions of the fractions derived from cultures grown under both conditions, are presented. A soluble, carbon monoxide-binding cytochrome c was found, and this appears similar to those found recently in Beneckea natiegens, methylotrophic bacteria and the marine pseudomonad B16."} {"id": "PMID:172599", "title": "Genes involved in the uptake and catabolism of gluconate by Escherichia coli.", "content": "The isolation and properties of a mutant of Escherichia coli K12 that is totally unable to take up and utilize gluconate are described. Genetical analysis shows this phenotype to be associated with two lesions. One phenotype, designated GntM-, is the result of a mutation in a gene co-transducible with malA; the other, designated GNTS-, is the result of a mutation in a gene (GntS) co-transducible with fdp. The GntS--phenotype differs little from that of wild-type cells, but GntM- GntS+ organisms grow on gluconate only after a prolonged lag and form a gluconate uptake system that is strongly repressed by pyruvate. Moreover, such GntM- mutants readily give rise to further mutants that form a gluconate uptake system, gluconate kinase and 6-phosphogluconate dehydratase consititutively; in partial diploids, this constitutivity is recessive to the inducible character. It is postulated that the GntM- phenotype is due to malfunction of a negative control gene gntR, and that gntS+ specifies the activity of a gluconate uptake system.", "contents": "Genes involved in the uptake and catabolism of gluconate by Escherichia coli. The isolation and properties of a mutant of Escherichia coli K12 that is totally unable to take up and utilize gluconate are described. Genetical analysis shows this phenotype to be associated with two lesions. One phenotype, designated GntM-, is the result of a mutation in a gene co-transducible with malA; the other, designated GNTS-, is the result of a mutation in a gene (GntS) co-transducible with fdp. The GntS--phenotype differs little from that of wild-type cells, but GntM- GntS+ organisms grow on gluconate only after a prolonged lag and form a gluconate uptake system that is strongly repressed by pyruvate. Moreover, such GntM- mutants readily give rise to further mutants that form a gluconate uptake system, gluconate kinase and 6-phosphogluconate dehydratase consititutively; in partial diploids, this constitutivity is recessive to the inducible character. It is postulated that the GntM- phenotype is due to malfunction of a negative control gene gntR, and that gntS+ specifies the activity of a gluconate uptake system."} {"id": "PMID:172601", "title": "The activity of polymyxins against dense populations of Escherichia coli.", "content": "The activities of polymyxin B sulphate, colistin (polymyxin E) sulphate and their sulphomethyl derivatives were compared by continuous turbidimetric monitoring of dense cultures of an Escherichia coli strain exposed to these agents. Judged by the concentration of antibiotic which caused a rapid fall in opacity of the culture, polymyxin B sulphate and colistin sulphate had similar activities, but the sulphomethyl compounds differed considerably: sulphomyxin sodium induced lysis of the culture at a concentration four times that of the parent compound, whereas colistin sulphomethate sodium induced a delayed fall in opacity consistent with recruitment of activity as the inactive sulphomethyl derivative was broken down to the parent compound. Durign overnight incubation, regrowth of cultures which had initially succumbed to polymyxin action occurred, apparently due to the selection of phenotypically resistant variants from within the population. In this way cultures could easily be adapted to growth in concentrations of antibiotic well above the conventionally-determined minimum inhibitory concentration. The comparative ease of adaptation was in the order: colistin sulphomethate greater than sulphomyxin greater than colistin sulphate greater than polymyxin B sulphate.", "contents": "The activity of polymyxins against dense populations of Escherichia coli. The activities of polymyxin B sulphate, colistin (polymyxin E) sulphate and their sulphomethyl derivatives were compared by continuous turbidimetric monitoring of dense cultures of an Escherichia coli strain exposed to these agents. Judged by the concentration of antibiotic which caused a rapid fall in opacity of the culture, polymyxin B sulphate and colistin sulphate had similar activities, but the sulphomethyl compounds differed considerably: sulphomyxin sodium induced lysis of the culture at a concentration four times that of the parent compound, whereas colistin sulphomethate sodium induced a delayed fall in opacity consistent with recruitment of activity as the inactive sulphomethyl derivative was broken down to the parent compound. Durign overnight incubation, regrowth of cultures which had initially succumbed to polymyxin action occurred, apparently due to the selection of phenotypically resistant variants from within the population. In this way cultures could easily be adapted to growth in concentrations of antibiotic well above the conventionally-determined minimum inhibitory concentration. The comparative ease of adaptation was in the order: colistin sulphomethate greater than sulphomyxin greater than colistin sulphate greater than polymyxin B sulphate."} {"id": "PMID:172602", "title": "Loss of cytochrome oxidase in Saccharomyces cerevisiae during inhibition of mitochondrial protein synthesis by erythromycin and chloramphenicol.", "content": "There is a major reduction in respiratory competence, and inhibitionof growth, several hours after the addition of erythromycin or chloramphenicol to Saccharomyces cerevisiae growing in medium containing a non-fermentable carbon source. Spectrographic evidence is presented for a loss of cytochrome oxidase as a consequence of the antibiotic treatment. This loss is prevented by cyanide or oligomycin. When glucose is added, however, the loss occurs irrespective of the presence of the respiratory inhibitors. Cycloheximide does not affect respiratory competence or cause loss of cytochrome oxidase, and it prevents the loss elicited by erythromycin if both compounds are added together. However, if cycloheximide is added some time after the addition of erythromycin, it fails to block the response to the latter drug. The results cannot be accounted for on the basis of the segregation of a finite number of mitochondria into an increasing number of progeny cells but, rather, suggest that the mitochondria are modified during growth in chloramphenicol or erythromycin.", "contents": "Loss of cytochrome oxidase in Saccharomyces cerevisiae during inhibition of mitochondrial protein synthesis by erythromycin and chloramphenicol. There is a major reduction in respiratory competence, and inhibitionof growth, several hours after the addition of erythromycin or chloramphenicol to Saccharomyces cerevisiae growing in medium containing a non-fermentable carbon source. Spectrographic evidence is presented for a loss of cytochrome oxidase as a consequence of the antibiotic treatment. This loss is prevented by cyanide or oligomycin. When glucose is added, however, the loss occurs irrespective of the presence of the respiratory inhibitors. Cycloheximide does not affect respiratory competence or cause loss of cytochrome oxidase, and it prevents the loss elicited by erythromycin if both compounds are added together. However, if cycloheximide is added some time after the addition of erythromycin, it fails to block the response to the latter drug. The results cannot be accounted for on the basis of the segregation of a finite number of mitochondria into an increasing number of progeny cells but, rather, suggest that the mitochondria are modified during growth in chloramphenicol or erythromycin."} {"id": "PMID:172608", "title": "Alveolar hypoventilation and hyperosmnia in myotonic dystrophy.", "content": "A case of myotonic dystrophy accompanied by alveolar hypoventilation and hypersomnia is presented. Radiological studies and EMG examination of the intercostal muscles demonstrated that the respiratory muscles were affected by the disease, while polygraphic recordings showed that the alveolar hypoventilation and pulmonary hypertension worsened during sleep. The hypersomnia preceded the appearance of clinical signs of the muscular disease by many years and persisted even after treatment when the blood gas analysis values were greatly improved. During both diurnal and nocturnal sleep, the patient frequently fell asleep directly into a REM stage. The possibility is discussed that, concomitant with the respiratory musculature involvement, there is an alteration in the central nervous system in myotonic dystrophy which is at least partially responsible for both the alveolar hypoventilation and the hypersomnia.", "contents": "Alveolar hypoventilation and hyperosmnia in myotonic dystrophy. A case of myotonic dystrophy accompanied by alveolar hypoventilation and hypersomnia is presented. Radiological studies and EMG examination of the intercostal muscles demonstrated that the respiratory muscles were affected by the disease, while polygraphic recordings showed that the alveolar hypoventilation and pulmonary hypertension worsened during sleep. The hypersomnia preceded the appearance of clinical signs of the muscular disease by many years and persisted even after treatment when the blood gas analysis values were greatly improved. During both diurnal and nocturnal sleep, the patient frequently fell asleep directly into a REM stage. The possibility is discussed that, concomitant with the respiratory musculature involvement, there is an alteration in the central nervous system in myotonic dystrophy which is at least partially responsible for both the alveolar hypoventilation and the hypersomnia."} {"id": "PMID:172609", "title": "Significance of muscle biopsies in neuronal ceroid-lipofuscinoses.", "content": "Muscle specimens obtained at necropsy from four cases of neuronal ceroid-lipofuscinosis (NCL), three of the juvenile and one of the late infantile type, and a muscle biopsy from a fifth patient with the juvenile type of NCL, all showed curvilinear bodies typical of NCL within the muscle fibres. The pigments were autofluorescent. It appears that skeletal muscle is a reliable tissue source for the diagnosis of these disorders by biopsy.", "contents": "Significance of muscle biopsies in neuronal ceroid-lipofuscinoses. Muscle specimens obtained at necropsy from four cases of neuronal ceroid-lipofuscinosis (NCL), three of the juvenile and one of the late infantile type, and a muscle biopsy from a fifth patient with the juvenile type of NCL, all showed curvilinear bodies typical of NCL within the muscle fibres. The pigments were autofluorescent. It appears that skeletal muscle is a reliable tissue source for the diagnosis of these disorders by biopsy."} {"id": "PMID:172610", "title": "An ultramicroscopic study of the skin in the diagnosis of the infantile and late infantile types of ceroid-lipofuscinosis.", "content": "A skin biopsy was carried out in two children suffering from early infantile (Santavuori) and late infantile (Jansky-Bielschowsky) types of ceroid-lipofuscinosis. In both cases cytoplasmic inclusions, identical with those found in neurones, were present in the skin. Skin biopsy thus appears as a simple technique for the diagnosis of the ceroid-lipofuscinoses.", "contents": "An ultramicroscopic study of the skin in the diagnosis of the infantile and late infantile types of ceroid-lipofuscinosis. A skin biopsy was carried out in two children suffering from early infantile (Santavuori) and late infantile (Jansky-Bielschowsky) types of ceroid-lipofuscinosis. In both cases cytoplasmic inclusions, identical with those found in neurones, were present in the skin. Skin biopsy thus appears as a simple technique for the diagnosis of the ceroid-lipofuscinoses."} {"id": "PMID:172611", "title": "Effects of collagenase upon the intervertebral disc in monkeys.", "content": "The authors studied 5 rhesus monkeys for the effects of annulotomy, with or without the addition of a bacterially-derived collagenase into the nuclear-evacuated centrum of lumbar intervertebral discs. The animals were sacrificed from 3 weeks to 21 months after the single or staged double procedures. The earliest radiographic changes were loss of height of the interspace at 7 days, erosion of the vertebral body margins at 3 weeks, malalignment at 6 weeks, osteophytic formation at 3 1/2 months, sclerosis of vertebral body surfaces at 9 1/2 months, and fusion of adjacent vertebral bodies at 13 1/2 months. Pathological changes included early loss of disc convexity, focal new home formation, osteophytic new growth, through-and-through bone formation, irregular cystification, and disc replacement by hyaline fibrous tissue. Changes were reminiscent of those seen in humans with naturally acquired disc disease or aging of the disc. Injuries were produced in a tissue that probably has a limited scope of variation in reaction to insult.", "contents": "Effects of collagenase upon the intervertebral disc in monkeys. The authors studied 5 rhesus monkeys for the effects of annulotomy, with or without the addition of a bacterially-derived collagenase into the nuclear-evacuated centrum of lumbar intervertebral discs. The animals were sacrificed from 3 weeks to 21 months after the single or staged double procedures. The earliest radiographic changes were loss of height of the interspace at 7 days, erosion of the vertebral body margins at 3 weeks, malalignment at 6 weeks, osteophytic formation at 3 1/2 months, sclerosis of vertebral body surfaces at 9 1/2 months, and fusion of adjacent vertebral bodies at 13 1/2 months. Pathological changes included early loss of disc convexity, focal new home formation, osteophytic new growth, through-and-through bone formation, irregular cystification, and disc replacement by hyaline fibrous tissue. Changes were reminiscent of those seen in humans with naturally acquired disc disease or aging of the disc. Injuries were produced in a tissue that probably has a limited scope of variation in reaction to insult."} {"id": "PMID:172612", "title": "Measurement of acute myocardial infarcts in dogs with 99mTc-stannous pyrophosphate scintigrams.", "content": "Myocardial scintigrams using 99mTc-stannous pyrophosphate (99mTc-PYP) can be used to measure myocardial infarcts produced in dogs by proximal ligation of the left anterior descending coronary artery. Seven dogs had 99mTc-PYP myocardial scintigraphy performed 24--32 hr after ligation of the proximal left anterior artery. In each dog the scintigrams showed increased 99mTc-PYP uptake in the distribution of the artery. The scintigraphically visible areas of infarction, measured using interactive computer-aided techniques, were compared subsequently with independent histologic measurements of myocardial infarct size. Several methods for using the area measurements to estimate infarct size were tested. The most successful method (r = 0.92, p less than 0.01) assumed a linear relationship between the largest scintigraphic infarct area and the histologically determined infarct weight. The results suggest that 99mTc-PYP myocardial scintigrams provide a useful noninvasive method for measuring infarct size in dogs with proximal ligation of the left anterior descending coronary artery.", "contents": "Measurement of acute myocardial infarcts in dogs with 99mTc-stannous pyrophosphate scintigrams. Myocardial scintigrams using 99mTc-stannous pyrophosphate (99mTc-PYP) can be used to measure myocardial infarcts produced in dogs by proximal ligation of the left anterior descending coronary artery. Seven dogs had 99mTc-PYP myocardial scintigraphy performed 24--32 hr after ligation of the proximal left anterior artery. In each dog the scintigrams showed increased 99mTc-PYP uptake in the distribution of the artery. The scintigraphically visible areas of infarction, measured using interactive computer-aided techniques, were compared subsequently with independent histologic measurements of myocardial infarct size. Several methods for using the area measurements to estimate infarct size were tested. The most successful method (r = 0.92, p less than 0.01) assumed a linear relationship between the largest scintigraphic infarct area and the histologically determined infarct weight. The results suggest that 99mTc-PYP myocardial scintigrams provide a useful noninvasive method for measuring infarct size in dogs with proximal ligation of the left anterior descending coronary artery."} {"id": "PMID:172613", "title": "Effect of unilateral pulmonary hypovascularity on the bone scan: case report.", "content": "Two patients who had decreased pulmonary artery blood flow to the right lung showed increased clarity of rib detail on a bone scan over the affected hemithorax as contrasted with the uninvolved side. Decreased blood background is postulated to result in enhancement of rib detail on the affected side.", "contents": "Effect of unilateral pulmonary hypovascularity on the bone scan: case report. Two patients who had decreased pulmonary artery blood flow to the right lung showed increased clarity of rib detail on a bone scan over the affected hemithorax as contrasted with the uninvolved side. Decreased blood background is postulated to result in enhancement of rib detail on the affected side."} {"id": "PMID:172614", "title": "Ovarian carcinoma imaged by 99mTc-pyrophosphate: case report.", "content": "An ovarian carcinoma which avidly accumulated 99mTc-pyrophosphate was imaged during a bone scan. The primary tumor and its implants over the liver surface were both visualized. Although imaging of such an ovarian malignancy has not been previously reported, it offers a potential method for assessing neoplastic size and spread.", "contents": "Ovarian carcinoma imaged by 99mTc-pyrophosphate: case report. An ovarian carcinoma which avidly accumulated 99mTc-pyrophosphate was imaged during a bone scan. The primary tumor and its implants over the liver surface were both visualized. Although imaging of such an ovarian malignancy has not been previously reported, it offers a potential method for assessing neoplastic size and spread."} {"id": "PMID:172616", "title": "Enzyme activities in the epidermis of zinc-deficient rats.", "content": "Fifteen enzymes participating in epidermal energy metabolism in zinc-deficient and -supplemented rats were assayed utilizing fluorometric microchemical techniques. In the zinc-deficient group, the activities of six enzymes catalyzing glycolysis decreased by 30 to 50% of the control; the most dramatic decreases were found in phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Zinc deficiency caused a 31% decrease in the activity of glucose-6-phosphate dehydrogenase, a 63% decrease in fumarate hydratase, a 46% decrease in glutamate dehydrogenase, and a 30 to 40% decrease in aminotransferases.", "contents": "Enzyme activities in the epidermis of zinc-deficient rats. Fifteen enzymes participating in epidermal energy metabolism in zinc-deficient and -supplemented rats were assayed utilizing fluorometric microchemical techniques. In the zinc-deficient group, the activities of six enzymes catalyzing glycolysis decreased by 30 to 50% of the control; the most dramatic decreases were found in phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Zinc deficiency caused a 31% decrease in the activity of glucose-6-phosphate dehydrogenase, a 63% decrease in fumarate hydratase, a 46% decrease in glutamate dehydrogenase, and a 30 to 40% decrease in aminotransferases."} {"id": "PMID:172617", "title": "Effects of quantity and quality of dietary protein and variation in certain enzyme activities on glucose metabolism in the rat.", "content": "This study attempted to determine whether the quantity and the quality of protein intake could influence the activity of some enzymes involved in carbohydrate metabolism. Thus, adult rats were fed for 23 days a diet containing different levels (10 to 70%) and qualities (casein, wheat gluten, and egg yolk) of protein. Variations in liver enzyme activities of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), glucose-6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were studied. Also the changes in enzyme activities were compared with changes in food intake and body weight gain. Increasing the protein level produced a progressive fall in the activities of ME and PK. The decrease in PK activity was greater when the biological value of the dietary proteins was higher (P less than 0.05). On the other hand, the activities of G6PDH and PEPCK increased as the protein level increased. The activity of G6Pase was unchanged. The relationship between the two opposing enzyme activities PK and PEPCK, in relation to protein intake, shows that for each protein studied, the equilibrium between glycolysis and gluconeogenesis was obtained at different protein intakes (1.5, 1.9, and 2.2 g of protein/day/100 g of body weight, respectively, for egg yolk, casein, and wheat gluten) regardless of daily consumption of energy as carbohydrate, which are similar (8 to 9 kcal/day/100 g of body weight). This equilibrium also corresponded to the maximum weight gain (5 g) of the experimental animals. In conclusion, the experimental method used permits a simultaneous assessment of the protein and carbohydrate requirements ensuring the best weight gain in young adult rats.", "contents": "Effects of quantity and quality of dietary protein and variation in certain enzyme activities on glucose metabolism in the rat. This study attempted to determine whether the quantity and the quality of protein intake could influence the activity of some enzymes involved in carbohydrate metabolism. Thus, adult rats were fed for 23 days a diet containing different levels (10 to 70%) and qualities (casein, wheat gluten, and egg yolk) of protein. Variations in liver enzyme activities of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), glucose-6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were studied. Also the changes in enzyme activities were compared with changes in food intake and body weight gain. Increasing the protein level produced a progressive fall in the activities of ME and PK. The decrease in PK activity was greater when the biological value of the dietary proteins was higher (P less than 0.05). On the other hand, the activities of G6PDH and PEPCK increased as the protein level increased. The activity of G6Pase was unchanged. The relationship between the two opposing enzyme activities PK and PEPCK, in relation to protein intake, shows that for each protein studied, the equilibrium between glycolysis and gluconeogenesis was obtained at different protein intakes (1.5, 1.9, and 2.2 g of protein/day/100 g of body weight, respectively, for egg yolk, casein, and wheat gluten) regardless of daily consumption of energy as carbohydrate, which are similar (8 to 9 kcal/day/100 g of body weight). This equilibrium also corresponded to the maximum weight gain (5 g) of the experimental animals. In conclusion, the experimental method used permits a simultaneous assessment of the protein and carbohydrate requirements ensuring the best weight gain in young adult rats."} {"id": "PMID:172618", "title": "Synovial sarcoma of the neck: report of case.", "content": "Synovial sarcoma is an uncommon neoplasm that usually arises in the extremities and rarely in the head and neck. A case arising in the neck has been reported herein. The tumor is composed of two intimately associated cellular patterns; one resembles synovial structures and the other resembles fibrosarcoma. The tumor is fairly slow growing and is fairly well circumscribed but not actually encapsulated. There is a predilection for males; most occur in the third through fifth decades of life. Recurrence follows inadequate therapy. Although local excision was the therapy used in this case, the patient is alive and free of disease 30 months postoperatively.", "contents": "Synovial sarcoma of the neck: report of case. Synovial sarcoma is an uncommon neoplasm that usually arises in the extremities and rarely in the head and neck. A case arising in the neck has been reported herein. The tumor is composed of two intimately associated cellular patterns; one resembles synovial structures and the other resembles fibrosarcoma. The tumor is fairly slow growing and is fairly well circumscribed but not actually encapsulated. There is a predilection for males; most occur in the third through fifth decades of life. Recurrence follows inadequate therapy. Although local excision was the therapy used in this case, the patient is alive and free of disease 30 months postoperatively."} {"id": "PMID:172619", "title": "The pathology of type II skeletal muscle glycogenosis. A light and electron-microscopic study.", "content": "Muscle biopsies were obtained from three infants under the age of 12 mth, each of whom was diagnosed as having Pompe's disease. The biopsies revealed a severe vacuolar myopathy with accumulation of large amounts of PAS positive material within the muscle fibres, changes similar to those in adult cases of the disease. In addition large amounts of metachromatic material were found within the muscle fibres in all three cases and in two of them scattered, rather sparse perivascular lymphocytic infiltrates were seen in the interstitial tissue. Review of material previously obtained from two adult cases showed no accumulation of metachromatic material in the older case and only moderate amounts in the younger. However, dense interstitial lymphocytic infiltrates were seen in the former, some concentrated around small vessels. These observations suggest that the pathogenesis of the muscle disorder in acid maltase deficiency may not depend on abnormal glycogen storage only.", "contents": "The pathology of type II skeletal muscle glycogenosis. A light and electron-microscopic study. Muscle biopsies were obtained from three infants under the age of 12 mth, each of whom was diagnosed as having Pompe's disease. The biopsies revealed a severe vacuolar myopathy with accumulation of large amounts of PAS positive material within the muscle fibres, changes similar to those in adult cases of the disease. In addition large amounts of metachromatic material were found within the muscle fibres in all three cases and in two of them scattered, rather sparse perivascular lymphocytic infiltrates were seen in the interstitial tissue. Review of material previously obtained from two adult cases showed no accumulation of metachromatic material in the older case and only moderate amounts in the younger. However, dense interstitial lymphocytic infiltrates were seen in the former, some concentrated around small vessels. These observations suggest that the pathogenesis of the muscle disorder in acid maltase deficiency may not depend on abnormal glycogen storage only."} {"id": "PMID:172621", "title": "Lethality of disrupted intestinal lamina propia cells for Trichinella spiralis in vitro.", "content": "The possible direct role of inflammatory cells in resistance to Trichinella spiralis was studied by observing the effects of lamina propria cells from the small intestine (LP cells) of immunized rats on various stages of the parasite. Effects produced by physically disrupted cells were compared to those produced by intact cells on worms exposed to phytohemagglutinin or immune serum. LP cells were isolated from the rat intestine by collagenase digestion of everted gut segments that were previously denuded of epithelium by treatment with hyaluronidase. Disrupted cells, but not intact ones, selectively killed T. spiralis juvenile and adult worms in vitro, whereas larvae were unaffected by similar treatment. Attempts to identify the lethal component of disrupted cells led to an evaluation of the enzyme, peroxidase. Mucosal peroxidase is localized in LP cells and its activity increases several-fold during intestinal trichinosis. It is presumed to be myeloperoxidase, a particulate-bound enzyme of myeloid-derived leukocytes that functions as part of a potent antimicrobial system in combination with H2O2 and a halide. Results indicated that the vermicidal component of LP cells was associated with the pellet fraction of disrupted centrifuged LP cells, but was not linked to a peroxidase-H2O2-halide system.", "contents": "Lethality of disrupted intestinal lamina propia cells for Trichinella spiralis in vitro. The possible direct role of inflammatory cells in resistance to Trichinella spiralis was studied by observing the effects of lamina propria cells from the small intestine (LP cells) of immunized rats on various stages of the parasite. Effects produced by physically disrupted cells were compared to those produced by intact cells on worms exposed to phytohemagglutinin or immune serum. LP cells were isolated from the rat intestine by collagenase digestion of everted gut segments that were previously denuded of epithelium by treatment with hyaluronidase. Disrupted cells, but not intact ones, selectively killed T. spiralis juvenile and adult worms in vitro, whereas larvae were unaffected by similar treatment. Attempts to identify the lethal component of disrupted cells led to an evaluation of the enzyme, peroxidase. Mucosal peroxidase is localized in LP cells and its activity increases several-fold during intestinal trichinosis. It is presumed to be myeloperoxidase, a particulate-bound enzyme of myeloid-derived leukocytes that functions as part of a potent antimicrobial system in combination with H2O2 and a halide. Results indicated that the vermicidal component of LP cells was associated with the pellet fraction of disrupted centrifuged LP cells, but was not linked to a peroxidase-H2O2-halide system."} {"id": "PMID:172623", "title": "Acylation of phenol by cyclic and acyclic anhydrides in anhydrous acetic acid.", "content": "Acylation of phenol with succinic, glutaric, trans-1,2-cyclohexanedicarboxylic, maleic, phthalic, and cis-1,2-cyclohexanedicarboxylic anhydrides in anhydrous acetic acid generally resulted in phenyl acetate as the major product. The formation of phenyl acetate as the major reaction product could be rationalized as being due to the reactivity of the cyclic anhydrides with acetic acid to form acetic anhydride as well as the greater reactivity of phenol with formed acetic anhydride than with the cyclic anhydride.", "contents": "Acylation of phenol by cyclic and acyclic anhydrides in anhydrous acetic acid. Acylation of phenol with succinic, glutaric, trans-1,2-cyclohexanedicarboxylic, maleic, phthalic, and cis-1,2-cyclohexanedicarboxylic anhydrides in anhydrous acetic acid generally resulted in phenyl acetate as the major product. The formation of phenyl acetate as the major reaction product could be rationalized as being due to the reactivity of the cyclic anhydrides with acetic acid to form acetic anhydride as well as the greater reactivity of phenol with formed acetic anhydride than with the cyclic anhydride."} {"id": "PMID:172624", "title": "Effects of choroid plexus peptide IIF on adenylate cyclase and 3',5'-cyclic adenosine monophosphate in adipose tissue.", "content": "Two hypophyseal lipolytic peptides, adrenocorticotropin (ACTH) and beta-melanocyte-stimulating hormone (beta-MSH), and the extrhypophyseal lipolytic peptide IIF, were compared with regard to their effects on free fatty acid production and 3',5'-cyclic adenosine monophosphate (cAMP) concentration in isolated rabbit and rat adipose tissue, and on adenylate cyclase activity in the tissue homogenates. ACTH at concentrations of 0.01 mug/ml or more increased lipolysis and cAMP levels in both tissues. beta-MSH at concentrations of 0.001 mug/ml or more increased lipolysis and cAMP in the rabbit tissue, but a concentration of 10 mug/ml did not stimulate lipolysis and did not alter nucleotide concentration in the rat tissue. Peptide IIF at 0.01 mug/ml or more stimulated lipolysis in rabbit adipose tissue and caused an accumulation of cAMP. A concentration of 100 mug/ml failed to stimulate free fatty acid production in the rat tissue and the cAMP level was also unaffected. In a medium containing 7.6 mEq/l of Mg++ and no Ca++, ACTH at 0.1 mug/ml or more stimulated adenylate cyclase activity in both rabbit and rat adipose homogenates by 6- to 12-fold. This effect was inhibited when Mg++ was replaced by Ca++, Na+ or K+. beta-MSH stimulated adenylate cyclase in rabbit, but not in rat, adipose homogenate in Mg++-containing incubation midium; again, the effect on rabbit adenylate cyclase was suppressed when Mg++ was replaced by Ca++, Na+ or K+. Peptide IIF failed to influence adenylate cyclase in the rabbit tissue homogenate in the Mg++-containing, Ca++-free medium; but when the medium contained 7.6 mEq/l of Ca++ in place of Mg++, 0.1 mug/ml or more of IIF caused a 4- to 15-fold increase in cyclase activity. IIF did not affect cyclase in the rat tissue homogenate in the presence or absence of Ca++. The data are consistent with the conclusion that extrahypophyseal lipolytic peptide IIF, as well as hypophyseal peptides ACTH and beta-MSH, accelerates lipolysis in susceptible adipocytes by stimulating adenylate cyclase to produce cAMP. The effect of IIF on cyclase requires the presence of exogenous Ca++; that of ACTH and beta-MSH requires exogenous Mg++.", "contents": "Effects of choroid plexus peptide IIF on adenylate cyclase and 3',5'-cyclic adenosine monophosphate in adipose tissue. Two hypophyseal lipolytic peptides, adrenocorticotropin (ACTH) and beta-melanocyte-stimulating hormone (beta-MSH), and the extrhypophyseal lipolytic peptide IIF, were compared with regard to their effects on free fatty acid production and 3',5'-cyclic adenosine monophosphate (cAMP) concentration in isolated rabbit and rat adipose tissue, and on adenylate cyclase activity in the tissue homogenates. ACTH at concentrations of 0.01 mug/ml or more increased lipolysis and cAMP levels in both tissues. beta-MSH at concentrations of 0.001 mug/ml or more increased lipolysis and cAMP in the rabbit tissue, but a concentration of 10 mug/ml did not stimulate lipolysis and did not alter nucleotide concentration in the rat tissue. Peptide IIF at 0.01 mug/ml or more stimulated lipolysis in rabbit adipose tissue and caused an accumulation of cAMP. A concentration of 100 mug/ml failed to stimulate free fatty acid production in the rat tissue and the cAMP level was also unaffected. In a medium containing 7.6 mEq/l of Mg++ and no Ca++, ACTH at 0.1 mug/ml or more stimulated adenylate cyclase activity in both rabbit and rat adipose homogenates by 6- to 12-fold. This effect was inhibited when Mg++ was replaced by Ca++, Na+ or K+. beta-MSH stimulated adenylate cyclase in rabbit, but not in rat, adipose homogenate in Mg++-containing incubation midium; again, the effect on rabbit adenylate cyclase was suppressed when Mg++ was replaced by Ca++, Na+ or K+. Peptide IIF failed to influence adenylate cyclase in the rabbit tissue homogenate in the Mg++-containing, Ca++-free medium; but when the medium contained 7.6 mEq/l of Ca++ in place of Mg++, 0.1 mug/ml or more of IIF caused a 4- to 15-fold increase in cyclase activity. IIF did not affect cyclase in the rat tissue homogenate in the presence or absence of Ca++. The data are consistent with the conclusion that extrahypophyseal lipolytic peptide IIF, as well as hypophyseal peptides ACTH and beta-MSH, accelerates lipolysis in susceptible adipocytes by stimulating adenylate cyclase to produce cAMP. The effect of IIF on cyclase requires the presence of exogenous Ca++; that of ACTH and beta-MSH requires exogenous Mg++."} {"id": "PMID:172625", "title": "Effect of albuterol and terbutaline, synthetic beta adrenergic stimulants, on the cyclic 3',5'-adenosine monophosphate system in smooth muscle.", "content": "The effect of albuterol and terbutaline on the cyclic 3',5'-adenosine monophosphate (cAMP) system was studied in rat uterus, aorta and myocardium and in dog bronchus, and was compared to that of isoproterenol in order to determine whether the tissue specificity observed in their functional effects is reflected in their effect on the cAMP system. Tissue specimens were either homogenized in Tris buffer for enzyme activity measurements or incubated in Krebs-Ringer-bicarbonate medium with the test drugs. Both albuterol and terbutaline produce an increase in cAMP content in the tissues due to a direct effect on adenylate cyclase. This effect can be potentiated by a phosphodiesterase inhibitor and antagonized by a beta adrenergic blocking compound. The cAMP response to each beta adrenergic agonist differs in the tissues examined: in uterus and aorta where the maximal effects are idenitcal, the ED50 values may reflect differences in affinity which may account for the different cAMP response to the compounds at the lower concentrations. In bronchus and myocardium, both the maximum effect and ED50 values of the compounds are different. Albuterol and terbutaline increases cAMP content in bronchus significantly and have only a small effect on cAMP cont in myocardium, whereas isoproterenol increases cAMP level significantly in both tissues. The results indicate that the tissue specificity of albuterol and terbutaline may have its origin at the level of the cAMP system.", "contents": "Effect of albuterol and terbutaline, synthetic beta adrenergic stimulants, on the cyclic 3',5'-adenosine monophosphate system in smooth muscle. The effect of albuterol and terbutaline on the cyclic 3',5'-adenosine monophosphate (cAMP) system was studied in rat uterus, aorta and myocardium and in dog bronchus, and was compared to that of isoproterenol in order to determine whether the tissue specificity observed in their functional effects is reflected in their effect on the cAMP system. Tissue specimens were either homogenized in Tris buffer for enzyme activity measurements or incubated in Krebs-Ringer-bicarbonate medium with the test drugs. Both albuterol and terbutaline produce an increase in cAMP content in the tissues due to a direct effect on adenylate cyclase. This effect can be potentiated by a phosphodiesterase inhibitor and antagonized by a beta adrenergic blocking compound. The cAMP response to each beta adrenergic agonist differs in the tissues examined: in uterus and aorta where the maximal effects are idenitcal, the ED50 values may reflect differences in affinity which may account for the different cAMP response to the compounds at the lower concentrations. In bronchus and myocardium, both the maximum effect and ED50 values of the compounds are different. Albuterol and terbutaline increases cAMP content in bronchus significantly and have only a small effect on cAMP cont in myocardium, whereas isoproterenol increases cAMP level significantly in both tissues. The results indicate that the tissue specificity of albuterol and terbutaline may have its origin at the level of the cAMP system."} {"id": "PMID:172626", "title": "The aortic arch baroreceptor response to static and dynamic stretches in an isolated aorta-depressor nerve preparation of cats in vitro.", "content": "1. The aortic arch baroreceptors of cats were studied in an isolated aortic arch-depressor nerve preparation in vitro to analyse their transmission properties. 2. Sinusoidal length changes of varying amplitudes (0-34-1-2 mm) and frequencies (1-10 Hz) at a given pre-stretch were imposed on the isolated receptor zone to quantitate the velocity sensitivity of these receptors and to test the linearity of the system. 3. The receptor response was evaluated from the spike activity of single fibres of the depressor nerve in number of spikes per stimulus period, average discharge rate, instantaneous frequency, and phase angle between forcing function and instantaneous frequency. 4. The static response is characterized by a threshold, saturation range, and a relatively large linear part between these two non-linearities. 5. The aortic receptors exhibit rate sensitivity. Depending on the stimulus amplitude and frequency the phase angles between the forcing function and the instantaneous frequency ranged from -14 to -68 degrees. 6. The average discharge rate (spikes/sec) is sensitive to stimulus amplitude but not to stimulus frequency at near-threshold operation; in the linear part of the static response curve, the receptor response becomes independent of the stimulus mode. 7. The baroreceptors of the aorta share many properties with other mechanoreceptors of different species and organ systems, particularly with those of the rest of the circulation. They exhibit static and to some degree rate sensitivity and operate physiologically near their thresholds, i.e. the afferent arc of the baroreflexes is highly non-linear.", "contents": "The aortic arch baroreceptor response to static and dynamic stretches in an isolated aorta-depressor nerve preparation of cats in vitro. 1. The aortic arch baroreceptors of cats were studied in an isolated aortic arch-depressor nerve preparation in vitro to analyse their transmission properties. 2. Sinusoidal length changes of varying amplitudes (0-34-1-2 mm) and frequencies (1-10 Hz) at a given pre-stretch were imposed on the isolated receptor zone to quantitate the velocity sensitivity of these receptors and to test the linearity of the system. 3. The receptor response was evaluated from the spike activity of single fibres of the depressor nerve in number of spikes per stimulus period, average discharge rate, instantaneous frequency, and phase angle between forcing function and instantaneous frequency. 4. The static response is characterized by a threshold, saturation range, and a relatively large linear part between these two non-linearities. 5. The aortic receptors exhibit rate sensitivity. Depending on the stimulus amplitude and frequency the phase angles between the forcing function and the instantaneous frequency ranged from -14 to -68 degrees. 6. The average discharge rate (spikes/sec) is sensitive to stimulus amplitude but not to stimulus frequency at near-threshold operation; in the linear part of the static response curve, the receptor response becomes independent of the stimulus mode. 7. The baroreceptors of the aorta share many properties with other mechanoreceptors of different species and organ systems, particularly with those of the rest of the circulation. They exhibit static and to some degree rate sensitivity and operate physiologically near their thresholds, i.e. the afferent arc of the baroreflexes is highly non-linear."} {"id": "PMID:172627", "title": "Fusion of host cell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana-infected macrophages.", "content": "Secondary lysosomes of cultured mouse peritoneal macrophages were labeled with the electron-dense colloid saccharated iron oxide; the identity of the labeled structures was checked by the Gomori reaction for acid phosphatase. Amastigotes of Leishmania mexicana mexicana derived from mouse lesions were used to infect these macrophages in vitro. In electron micrographs of thin sections of infected macrophages the labeled secondary lysosomes were seen fused with the parasitophorous vacuoles without preventing subsequent multiplication of the parasites. A similar fusion probably occurs in vivo, and may provide a pathway through which not only nutrients but also drugs and host antibodies could reach the intracellular parasite.", "contents": "Fusion of host cell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana-infected macrophages. Secondary lysosomes of cultured mouse peritoneal macrophages were labeled with the electron-dense colloid saccharated iron oxide; the identity of the labeled structures was checked by the Gomori reaction for acid phosphatase. Amastigotes of Leishmania mexicana mexicana derived from mouse lesions were used to infect these macrophages in vitro. In electron micrographs of thin sections of infected macrophages the labeled secondary lysosomes were seen fused with the parasitophorous vacuoles without preventing subsequent multiplication of the parasites. A similar fusion probably occurs in vivo, and may provide a pathway through which not only nutrients but also drugs and host antibodies could reach the intracellular parasite."} {"id": "PMID:172629", "title": "Changes in lipase and phosphatase activities of rat spermatozoa in transit from the caput to the cauda epididymidis.", "content": "Rat spermatozoa from the cauda epididymidis, freed from their cytoplasmic droplets and acrosomes, were found to have a lower lipid content and to incorporate [14C]glucose into their glycerides and glycerophosphatides at a lower rate than spermatozoa from the caput epididymidis. Against the background of the activities of some glycolytic enzymes which remained constant the activity of alkaline phosphatase decreased in spermatozoa migrating through the epididymis, whereas the activity of monoglyceride lipase increased. The corresponding enzyme activities of non-flagellate germ cells of the testis were measured for comparison. The triglyceride lipase of non-flagellate germ cells and of spermatozoa from both caput and cauda epididymidis was activated by cyclic 3':5'-AMP.", "contents": "Changes in lipase and phosphatase activities of rat spermatozoa in transit from the caput to the cauda epididymidis. Rat spermatozoa from the cauda epididymidis, freed from their cytoplasmic droplets and acrosomes, were found to have a lower lipid content and to incorporate [14C]glucose into their glycerides and glycerophosphatides at a lower rate than spermatozoa from the caput epididymidis. Against the background of the activities of some glycolytic enzymes which remained constant the activity of alkaline phosphatase decreased in spermatozoa migrating through the epididymis, whereas the activity of monoglyceride lipase increased. The corresponding enzyme activities of non-flagellate germ cells of the testis were measured for comparison. The triglyceride lipase of non-flagellate germ cells and of spermatozoa from both caput and cauda epididymidis was activated by cyclic 3':5'-AMP."} {"id": "PMID:172631", "title": "Synthesis and evaluation of (Des-Asp1)angiotensin I as a precursor for (Des-Asp1)angiotensin II (\"Angiotensin III\").", "content": "The nonapeptide [des-Asp1]angiotensin I (IV), synthesized by Merrifield's solid-phase procedure, was tested as a possible substrate for the converting enzymes from porcine lung and plasma. IV, [des-Asp1]angiotensin II (III), [des-(Asp1,Arg2)]angiotensin II (V), [des-(Asp1,Arg2,Val3)]angiotensin II (VI), [Sar1,Ile8]angiotensin II (VII), and [des-Asp1,Ile8]angiotensin II (VIII) possessed 0.5, 20, 2, 0 less than 0.1, and less than 0.01% of the inotropic activity (rabbit atria), 1, 15, 5, 0, 3, and 0% secretory activity of the cat adrenal medulla, and 0.0, 150, 0.5, 3, and 10% of the adrenal steroidogenic activity of angiotensin II, respectively. When tested for their antagonistic activity in the above tissues, only VII and VIII were found to inhibit responses to angiotensin II. The pA2 values for VII and VIII were 8.31 and 10.0 in the adrenal cortex and 9.31 and 9.16 in the adrenal medulla, respectively. All these peptides were also tested as product inhibitors for the plasma and lung converting enzymes. With the plasma enzyme, the ID50 values were II, 1.6 X 10(-4) M; III, 5 X 10(-5) M; V, 1.2 X 10(-4) M; VI 5 X 10(-4) M; VII 5 X 10(-5) M; VIII, 5 X 10(-4) M. Thus, IV is a good substrate for converting enzymes from lung and plasma while all other compounds were inhibitors of these enzymes. The most potent inhibitors of converting enzyme were III followed by VII and VIII. With the exception of II and III, all the other analogs had very low intrinsic activities, per se. These results suggest (a) an alternate pathway for the formation of heptapeptide III, viz., by the action of converting enzyme on the nonapeptide IV, and (b) that III may also be acting as inhibitor of the converting enzyme by the feedback mechanism.", "contents": "Synthesis and evaluation of (Des-Asp1)angiotensin I as a precursor for (Des-Asp1)angiotensin II (\"Angiotensin III\"). The nonapeptide [des-Asp1]angiotensin I (IV), synthesized by Merrifield's solid-phase procedure, was tested as a possible substrate for the converting enzymes from porcine lung and plasma. IV, [des-Asp1]angiotensin II (III), [des-(Asp1,Arg2)]angiotensin II (V), [des-(Asp1,Arg2,Val3)]angiotensin II (VI), [Sar1,Ile8]angiotensin II (VII), and [des-Asp1,Ile8]angiotensin II (VIII) possessed 0.5, 20, 2, 0 less than 0.1, and less than 0.01% of the inotropic activity (rabbit atria), 1, 15, 5, 0, 3, and 0% secretory activity of the cat adrenal medulla, and 0.0, 150, 0.5, 3, and 10% of the adrenal steroidogenic activity of angiotensin II, respectively. When tested for their antagonistic activity in the above tissues, only VII and VIII were found to inhibit responses to angiotensin II. The pA2 values for VII and VIII were 8.31 and 10.0 in the adrenal cortex and 9.31 and 9.16 in the adrenal medulla, respectively. All these peptides were also tested as product inhibitors for the plasma and lung converting enzymes. With the plasma enzyme, the ID50 values were II, 1.6 X 10(-4) M; III, 5 X 10(-5) M; V, 1.2 X 10(-4) M; VI 5 X 10(-4) M; VII 5 X 10(-5) M; VIII, 5 X 10(-4) M. Thus, IV is a good substrate for converting enzymes from lung and plasma while all other compounds were inhibitors of these enzymes. The most potent inhibitors of converting enzyme were III followed by VII and VIII. With the exception of II and III, all the other analogs had very low intrinsic activities, per se. These results suggest (a) an alternate pathway for the formation of heptapeptide III, viz., by the action of converting enzyme on the nonapeptide IV, and (b) that III may also be acting as inhibitor of the converting enzyme by the feedback mechanism."} {"id": "PMID:172632", "title": "Synthesis of 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide and related 5'-deoxyimidazole ribonucleosides.", "content": "5-Amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (1, AICA ribonucleoside) was converted in two steps to 5-amino-1-(5-deoxy-5-iodo-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (3) which was hydrogenated in the presence of Pd/C to yield 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (4). The dehydration of 4 yielded 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carbonitrile (7). The compounds 3, 4, and 7 were deblocked with formic acid to furnish 5-amino-1-(5-deoxy-5-iodo-beta-D-ribofuranosyl)imidazole-4-carboxamide (6). 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (5), and 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (8), respectively. Compound 8 was acetylated and then deaminated to give 1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (11). The compounds 8 and 11 were converted into 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (9) and 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (12), respectively. The synthesis of 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (13) was achieved for the first time by the treatment of 11 with hydrogen peroxide in the presence of ammonium hydroxide. The compounds were tested for antibacterial, antifungal, and antiviral activity, with 5 and 6 significantly inhibitory to Staphylococcus aureus.", "contents": "Synthesis of 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide and related 5'-deoxyimidazole ribonucleosides. 5-Amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (1, AICA ribonucleoside) was converted in two steps to 5-amino-1-(5-deoxy-5-iodo-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (3) which was hydrogenated in the presence of Pd/C to yield 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (4). The dehydration of 4 yielded 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carbonitrile (7). The compounds 3, 4, and 7 were deblocked with formic acid to furnish 5-amino-1-(5-deoxy-5-iodo-beta-D-ribofuranosyl)imidazole-4-carboxamide (6). 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (5), and 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (8), respectively. Compound 8 was acetylated and then deaminated to give 1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (11). The compounds 8 and 11 were converted into 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (9) and 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (12), respectively. The synthesis of 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (13) was achieved for the first time by the treatment of 11 with hydrogen peroxide in the presence of ammonium hydroxide. The compounds were tested for antibacterial, antifungal, and antiviral activity, with 5 and 6 significantly inhibitory to Staphylococcus aureus."} {"id": "PMID:172633", "title": "Regulation of cellular calcium metabolism and calcium transport by calcitonin.", "content": "Calcitonin was studied in isolated kidney cells and in isolated mitochondria. A concentration of 10 ng/ml of synthetic calcitonin increases the cellular accumulation of 45Ca and the total cell calcium. The mitochondrial pool is increased several-fold. Kinetic analysis of the data shows that although the total cellular exchangeable calcium pool is enlarged, calcium influx and efflux are significantly depressed by calcitonin. The absence of phosphate or the presence of inhibitors of mitochondrial calcium transport completely abolish the effects of the hormone. In isolated mitochondria, the hormone stimulates the active calcium uptake and depresses the extramitochondrial calcium activity. Calcitonin counteracts the effects of cyclic AMP which stimulates the release of calcium from mitochondria and increases the extramitochondrial calcium activity. These data indicate that cellular calcium homeostasis is controlled by the mitochondrial calcium turnover. They suggest that calcitomin regulates the cell calcium metabolism and inhibits the transcellular calcium transport by stimulating the rate of calcium uptake by mitochondria which depresses cytoplasmic calcium activity.", "contents": "Regulation of cellular calcium metabolism and calcium transport by calcitonin. Calcitonin was studied in isolated kidney cells and in isolated mitochondria. A concentration of 10 ng/ml of synthetic calcitonin increases the cellular accumulation of 45Ca and the total cell calcium. The mitochondrial pool is increased several-fold. Kinetic analysis of the data shows that although the total cellular exchangeable calcium pool is enlarged, calcium influx and efflux are significantly depressed by calcitonin. The absence of phosphate or the presence of inhibitors of mitochondrial calcium transport completely abolish the effects of the hormone. In isolated mitochondria, the hormone stimulates the active calcium uptake and depresses the extramitochondrial calcium activity. Calcitonin counteracts the effects of cyclic AMP which stimulates the release of calcium from mitochondria and increases the extramitochondrial calcium activity. These data indicate that cellular calcium homeostasis is controlled by the mitochondrial calcium turnover. They suggest that calcitomin regulates the cell calcium metabolism and inhibits the transcellular calcium transport by stimulating the rate of calcium uptake by mitochondria which depresses cytoplasmic calcium activity."} {"id": "PMID:172634", "title": "Mechanism of inhibition of the proximal tubular isotonic fluid absorption by polylysine and other cationic polyamino acids.", "content": "The present study was initiated with the hope of clarifying the role of negative charges in the luminal brush border membrane in the overall process of trans-epithelial isotonic sodium and water absorption. Using micropuncture techniques, cationic polyamino acids such as polylysine (mol wt 100,000, 17,000 and 1,500-5,000, 1 mg/ml), tetralysine, polyornithine (mol wt 100,000, 1mg/ml), polyethyleneimine (2 mg/ml), polymyxin B (2 mg/ml), protamine sulfate (25 mg/ml) and histone (0.5 mg/ml) were perfused through the segments of rat kidney proximal tubule for 30 sec to 2 min. The rate of isotonic fluid absorption was measured before and after each perfusion with the Gertz's split drop method using Ringer's solution as a shrinking drop. Polylysine 100,000 and 17,000 and polyornithine were the most potent, inhibiting isotonic reabsorption by 93%. The sequence of inhibitory effect was: polylysine 100,000 congruent to polyornithine 100,000 congruent to polylysine 17,000 greater than polyethyleneimine greater than polylysine 1,500-5,000 congruent to polymyxin B greater than protamine sulfate congruent to histone. In contrast, tetralysine (2 mg/ml) showed no inhibitory effect. Electrical potential difference (p.d.) of the proximal tubular cells was destroyed within 10 sec of luminal perfusion with polylysine 100,000 (1 mg/ml). Simultaneously with the drop in p.d., electrical resistance of the luminal brush border membrane was nearly totally eliminated, whereas transepithelial input resistance remained unaltered. Furthermore, trypan blue dye was taken up by polylysine 100,000-perfused tubular cells but not by normal cells. Expanding drop analysis (mannitol solution as a split drop) was performed as a screening test to examine if the permeability for water and sodium in the lateral paracellular pathway is altered by polylysine 100,000. No significant difference was observed in the velocity of split drop expansion between untreated and polylysine-perfused tubules. A lower concentration of polylysine 100,000 (0.1 mg/ml) showed a much less inhibitory effect on fluid absorption and on cell p.d. These observations indicate that the strong inhibition on proximal tubular fluid absorption exerted by polylysine and perhaps also by other cationic polyamino acids is due not to modification of membrane negative charges but to the lysis of tubular cells by these polycations.", "contents": "Mechanism of inhibition of the proximal tubular isotonic fluid absorption by polylysine and other cationic polyamino acids. The present study was initiated with the hope of clarifying the role of negative charges in the luminal brush border membrane in the overall process of trans-epithelial isotonic sodium and water absorption. Using micropuncture techniques, cationic polyamino acids such as polylysine (mol wt 100,000, 17,000 and 1,500-5,000, 1 mg/ml), tetralysine, polyornithine (mol wt 100,000, 1mg/ml), polyethyleneimine (2 mg/ml), polymyxin B (2 mg/ml), protamine sulfate (25 mg/ml) and histone (0.5 mg/ml) were perfused through the segments of rat kidney proximal tubule for 30 sec to 2 min. The rate of isotonic fluid absorption was measured before and after each perfusion with the Gertz's split drop method using Ringer's solution as a shrinking drop. Polylysine 100,000 and 17,000 and polyornithine were the most potent, inhibiting isotonic reabsorption by 93%. The sequence of inhibitory effect was: polylysine 100,000 congruent to polyornithine 100,000 congruent to polylysine 17,000 greater than polyethyleneimine greater than polylysine 1,500-5,000 congruent to polymyxin B greater than protamine sulfate congruent to histone. In contrast, tetralysine (2 mg/ml) showed no inhibitory effect. Electrical potential difference (p.d.) of the proximal tubular cells was destroyed within 10 sec of luminal perfusion with polylysine 100,000 (1 mg/ml). Simultaneously with the drop in p.d., electrical resistance of the luminal brush border membrane was nearly totally eliminated, whereas transepithelial input resistance remained unaltered. Furthermore, trypan blue dye was taken up by polylysine 100,000-perfused tubular cells but not by normal cells. Expanding drop analysis (mannitol solution as a split drop) was performed as a screening test to examine if the permeability for water and sodium in the lateral paracellular pathway is altered by polylysine 100,000. No significant difference was observed in the velocity of split drop expansion between untreated and polylysine-perfused tubules. A lower concentration of polylysine 100,000 (0.1 mg/ml) showed a much less inhibitory effect on fluid absorption and on cell p.d. These observations indicate that the strong inhibition on proximal tubular fluid absorption exerted by polylysine and perhaps also by other cationic polyamino acids is due not to modification of membrane negative charges but to the lysis of tubular cells by these polycations."} {"id": "PMID:172635", "title": "Irreversible stimulation of adenylate cyclase activity of fat cell membranes of phosphoramidate and phosphonate analogs of GTP.", "content": "The ability of 5'-guanylylimidodiphosphate (Gpp(NH)p) to stimulate irreversibly the adenylate cyclease activity of fat cell membranes has been studied by preincubating the membranes with this or related analogs followed by assaying after thoroughly washing the membranes. Activation can occur in a simple Tris-HCl buffer, in the absence of added divalent cations and in the presence of EDTA. Dithiothreitol enhances the apparent degree of activation, perhaps by stabilization. The importance of utilizing optimal conditions for stabilizing enzyme activity, and of measuring the simultaneous changes in the control enzyme, is illustrated. The organomercurial, p-aminophenylmercuric acetate, inhibits profoundly the activity of the native as well as the Gpp(NH)p-stimulated adenylate cyclase, but in both cases subsequent exposure to dithiothreitol restores fully the original enzyme activity. However, the mercurial-inactivated enzyme does not react with Gpp(NP)p, as evidenced by the subsequent restoration of only the control enzyme activity upon exposure to dithiothreitol. Thus, reaction with Gpp(NH)p requires intact sulfhydryl groups, but the activated state is not irreversibly destroyed by the inactivation caused by sulfhydryl blockade. GTP and, less effectively, GDP and ATP inhibit activation by Gpp(NH)p, but interpretations are complicated by the facts that this inhibition is overcome with time and that GTP and ATP can protect potently from spontaneous inactivation. These two nucleotides can be used in the Gpp(NH)p preincubation to stabilize the enzyme. The Gpp(NH)p-activated enzyme cannot be reversed spontaneously during prolonged incubation at 30 degrees C in the absence or presence of GTP, ATP, MgCl2, glycine, dithiothreitol, NaF or EDTA. The strong nucleophile, neutral hydroxylamine, decreases the Gpp(NH)p-activated enzyme activity and no subsequent activation is detected upon re-exposure to the nucleotide.", "contents": "Irreversible stimulation of adenylate cyclase activity of fat cell membranes of phosphoramidate and phosphonate analogs of GTP. The ability of 5'-guanylylimidodiphosphate (Gpp(NH)p) to stimulate irreversibly the adenylate cyclease activity of fat cell membranes has been studied by preincubating the membranes with this or related analogs followed by assaying after thoroughly washing the membranes. Activation can occur in a simple Tris-HCl buffer, in the absence of added divalent cations and in the presence of EDTA. Dithiothreitol enhances the apparent degree of activation, perhaps by stabilization. The importance of utilizing optimal conditions for stabilizing enzyme activity, and of measuring the simultaneous changes in the control enzyme, is illustrated. The organomercurial, p-aminophenylmercuric acetate, inhibits profoundly the activity of the native as well as the Gpp(NH)p-stimulated adenylate cyclase, but in both cases subsequent exposure to dithiothreitol restores fully the original enzyme activity. However, the mercurial-inactivated enzyme does not react with Gpp(NP)p, as evidenced by the subsequent restoration of only the control enzyme activity upon exposure to dithiothreitol. Thus, reaction with Gpp(NH)p requires intact sulfhydryl groups, but the activated state is not irreversibly destroyed by the inactivation caused by sulfhydryl blockade. GTP and, less effectively, GDP and ATP inhibit activation by Gpp(NH)p, but interpretations are complicated by the facts that this inhibition is overcome with time and that GTP and ATP can protect potently from spontaneous inactivation. These two nucleotides can be used in the Gpp(NH)p preincubation to stabilize the enzyme. The Gpp(NH)p-activated enzyme cannot be reversed spontaneously during prolonged incubation at 30 degrees C in the absence or presence of GTP, ATP, MgCl2, glycine, dithiothreitol, NaF or EDTA. The strong nucleophile, neutral hydroxylamine, decreases the Gpp(NH)p-activated enzyme activity and no subsequent activation is detected upon re-exposure to the nucleotide."} {"id": "PMID:172636", "title": "Mechanism of activation of adenylate cyclase by Vibrio cholerae enterotoxin. Relations to the mode of activation by hormones.", "content": "The influence of Vibrio cholerae enterotoxin (choleragen) on the response of adenylate cyclase to hormones and GTP, and on the binding of 125I-labeled glucagon to membranes, has been examined primarily in rat adipocytes, but also in guinea pig ileal mucosa and rat liver. Incubation of fat cells with choleragen converts adenylate cyclase to a GTP-responsive state; (-)-isoproterenol has a similar effect when added directly to membranes. Choleragen also increases by two- to fivefold the apparent affinity of (-)-isoproterenol, ACTH, glucagon, and vasoactive intestinal polypeptide for the activation of adenylate cyclase. This effect on vasoactive intestinal polypeptide action is also seen with the enzyme of guinea pig ileal mucosa; the toxin-induced sensitivity to VIP may be relevant in the pathogenesis of cholera diarrhea. The apparent affinity of binding of 125I-labeled glucagon is increased about 1.5- to twofold in choleragen-treated liver and fat cell membranes. The effects of choleragen on the response of adenylate cyclase to hormones are independent of protein synthesis, and they are not simply a consequence to protracted stimulation of the enzyme in vivo or during preparation of the membranes. Activation of cyclase in rat erythrocytes by choleragen is not impaired by agents which disrupt microtubules or microfilaments, and it is still observed in cultured fibroblasts after completely suppressing protein synthesis with diphtheria toxin. Choleragen does not interact directly with hormone receptor sites. Simple occupation of the choleragen binding sites with the analog, choleragenoid, does not lead to any of the biological effects of the toxin.", "contents": "Mechanism of activation of adenylate cyclase by Vibrio cholerae enterotoxin. Relations to the mode of activation by hormones. The influence of Vibrio cholerae enterotoxin (choleragen) on the response of adenylate cyclase to hormones and GTP, and on the binding of 125I-labeled glucagon to membranes, has been examined primarily in rat adipocytes, but also in guinea pig ileal mucosa and rat liver. Incubation of fat cells with choleragen converts adenylate cyclase to a GTP-responsive state; (-)-isoproterenol has a similar effect when added directly to membranes. Choleragen also increases by two- to fivefold the apparent affinity of (-)-isoproterenol, ACTH, glucagon, and vasoactive intestinal polypeptide for the activation of adenylate cyclase. This effect on vasoactive intestinal polypeptide action is also seen with the enzyme of guinea pig ileal mucosa; the toxin-induced sensitivity to VIP may be relevant in the pathogenesis of cholera diarrhea. The apparent affinity of binding of 125I-labeled glucagon is increased about 1.5- to twofold in choleragen-treated liver and fat cell membranes. The effects of choleragen on the response of adenylate cyclase to hormones are independent of protein synthesis, and they are not simply a consequence to protracted stimulation of the enzyme in vivo or during preparation of the membranes. Activation of cyclase in rat erythrocytes by choleragen is not impaired by agents which disrupt microtubules or microfilaments, and it is still observed in cultured fibroblasts after completely suppressing protein synthesis with diphtheria toxin. Choleragen does not interact directly with hormone receptor sites. Simple occupation of the choleragen binding sites with the analog, choleragenoid, does not lead to any of the biological effects of the toxin."} {"id": "PMID:172637", "title": "Distribution of parathyroid hormone-stimulated adenylate cyclase in plasma membranes of cells of the kidney cortex.", "content": "Free flow electrophoresis was employed to separate renal cortical plasma membranes into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. During the separation adenylate cyclase activity was found to parallel the activity of Na+-K+-activated ATPase, an enzyme which is present in contraluminal but not in luminal membranes. In the basal-lateral membrane fraction the specific activities of adenylate cyclase and Na+-K+-activated ATPase were 4.4 and 4.6 times greater, respectively, than in the brush border fraction. The adenylate cyclase of the basal-lateral membrane fraction was specifically stimulated by parathyroid hormone which maximally increased enzyme activity eightfold. The biologically active (1-34) peptide fragment of paratyhroid hormone produced a 350% increase in adenylate cyclase activity. In contrast, calcitonin, epinephrine and vasopressin maximally stimulated the enzyme by only 55, 35 and 30%, respectively. These results indicate that adenylate cyclase, specifically stimulated by parathyroid hormone, is distributed preferentially in the contraluminal region of the plasma membrane of renal cortical epithelial cells.", "contents": "Distribution of parathyroid hormone-stimulated adenylate cyclase in plasma membranes of cells of the kidney cortex. Free flow electrophoresis was employed to separate renal cortical plasma membranes into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. During the separation adenylate cyclase activity was found to parallel the activity of Na+-K+-activated ATPase, an enzyme which is present in contraluminal but not in luminal membranes. In the basal-lateral membrane fraction the specific activities of adenylate cyclase and Na+-K+-activated ATPase were 4.4 and 4.6 times greater, respectively, than in the brush border fraction. The adenylate cyclase of the basal-lateral membrane fraction was specifically stimulated by parathyroid hormone which maximally increased enzyme activity eightfold. The biologically active (1-34) peptide fragment of paratyhroid hormone produced a 350% increase in adenylate cyclase activity. In contrast, calcitonin, epinephrine and vasopressin maximally stimulated the enzyme by only 55, 35 and 30%, respectively. These results indicate that adenylate cyclase, specifically stimulated by parathyroid hormone, is distributed preferentially in the contraluminal region of the plasma membrane of renal cortical epithelial cells."} {"id": "PMID:172638", "title": "Distribution of membrane-bound cyclic AMP-dependent protein kinase in plasma membranes of cells of the kidney cortex.", "content": "Renal cortical plasms membranes were separated by free flow electrophoresis into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. These membranes were found to contain an intrinsic, self-phosphorylating system which consists of a cyclic AMP-dependent protein kinase, a phosphorprotein phosphatase and the substrate(s) of these enzymes. The kinase, but not the phosphatase, was stimulated by cyclic AMP; maximal (1.7-fold) stimulation was effected at a cyclic AMP concentration of 0.1 muM. The degree of phosphorylation of the brush borders was six times greater than that of the basal-lateral membranes in the absence of cyclic AMP and 2.3-fold greater in the presence of cyclic AMP. This preferential phosphorylation of the luminal membrane by membrane-associated protein kinase(s) may play a role in the parathyroid hormone-mediated alterations of solute reabsorption in the proximal tubule.", "contents": "Distribution of membrane-bound cyclic AMP-dependent protein kinase in plasma membranes of cells of the kidney cortex. Renal cortical plasms membranes were separated by free flow electrophoresis into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. These membranes were found to contain an intrinsic, self-phosphorylating system which consists of a cyclic AMP-dependent protein kinase, a phosphorprotein phosphatase and the substrate(s) of these enzymes. The kinase, but not the phosphatase, was stimulated by cyclic AMP; maximal (1.7-fold) stimulation was effected at a cyclic AMP concentration of 0.1 muM. The degree of phosphorylation of the brush borders was six times greater than that of the basal-lateral membranes in the absence of cyclic AMP and 2.3-fold greater in the presence of cyclic AMP. This preferential phosphorylation of the luminal membrane by membrane-associated protein kinase(s) may play a role in the parathyroid hormone-mediated alterations of solute reabsorption in the proximal tubule."} {"id": "PMID:172654", "title": "Isolation of RNA transcripts from the entire Sendai viral genome.", "content": "Three classes of viral transcripts (18S, 24S, and 33S) were isolated from viral ribonucleoproteins in Sendai virus-infected cells. Hybridization studies with virion minus strand genome RNA demonstrated that the 18S RNA contained transcripts from 60% of the viral genome while the 33S RNA contained transcripts from the entire viral genome. Brief heat of ME2SO treatment of the 33S RNA demonstrated that this RNA was composed of two classes: RNA which continued to sediment at 33S (33S RNA) and 18S RNA aggregates (18S RNA). The 33S RNA was determined to be a transcript from the 40% of the viral genome not protected by the 18S RNA. The aggregated 18S RNA does not appear to be an artifact of isolation.", "contents": "Isolation of RNA transcripts from the entire Sendai viral genome. Three classes of viral transcripts (18S, 24S, and 33S) were isolated from viral ribonucleoproteins in Sendai virus-infected cells. Hybridization studies with virion minus strand genome RNA demonstrated that the 18S RNA contained transcripts from 60% of the viral genome while the 33S RNA contained transcripts from the entire viral genome. Brief heat of ME2SO treatment of the 33S RNA demonstrated that this RNA was composed of two classes: RNA which continued to sediment at 33S (33S RNA) and 18S RNA aggregates (18S RNA). The 33S RNA was determined to be a transcript from the 40% of the viral genome not protected by the 18S RNA. The aggregated 18S RNA does not appear to be an artifact of isolation."} {"id": "PMID:172655", "title": "Homology between avian oncornavirus RNAs and DNA from several avian species.", "content": "3H-labeled 35S RNA from avian myeloblastosis virus (AMV), Rous associated virus (RAV)-0, RAV-60, RAV-61, RAV-2, or B-77(w) was hybridized with an excess of cellular DNA from different avian species, i.e., normal or leukemic chickens, normal pheasants, turkeys, Japanese quails, or ducks. Approximately two to three copies of endogenous viral DNA were estimated to be present per diploid of normal chicken cell genome. In leukemic chicken myeloblasts induced by AMV, the number of viral sequences appeared to have doubled. The hybrids formed between viral RNA and DNA from leukemic chicken cells melted with a Tm 1 to 6 C higher than that of hybrids formed between viral RNA and normal chicken cell DNA. All of the viral RNAs tested, except RAV-61, hybridized the most with DNA from AMV-infected chicken cells, followed by DNA from normal chicken cells, and then pheasant DNA. RAV-61 RNA hybridized maximally (39%) with pheasant DNA, followed by DNA from leukemic (34%), and then normal (29%) chicken cells. All viral RNAs tested hybridized little with Japanese quail DNA (2 to 5%), turkey DNA (2 to 4%), or duck DNA (1%). DNA from normal chicken cells contained only 60 to 70% of the RAV-60 genetic information, and normal pheasant cells lacked some RAV-61 DNA sequences. RAV-60 and RAV-61 genomes were more homologous to the RAV-0 genome than to the genome of RAV-2, AMV, or B-77(s). RAV-60 and RAV-61 appear to be recombinants between endogenous and exogenous viruses.", "contents": "Homology between avian oncornavirus RNAs and DNA from several avian species. 3H-labeled 35S RNA from avian myeloblastosis virus (AMV), Rous associated virus (RAV)-0, RAV-60, RAV-61, RAV-2, or B-77(w) was hybridized with an excess of cellular DNA from different avian species, i.e., normal or leukemic chickens, normal pheasants, turkeys, Japanese quails, or ducks. Approximately two to three copies of endogenous viral DNA were estimated to be present per diploid of normal chicken cell genome. In leukemic chicken myeloblasts induced by AMV, the number of viral sequences appeared to have doubled. The hybrids formed between viral RNA and DNA from leukemic chicken cells melted with a Tm 1 to 6 C higher than that of hybrids formed between viral RNA and normal chicken cell DNA. All of the viral RNAs tested, except RAV-61, hybridized the most with DNA from AMV-infected chicken cells, followed by DNA from normal chicken cells, and then pheasant DNA. RAV-61 RNA hybridized maximally (39%) with pheasant DNA, followed by DNA from leukemic (34%), and then normal (29%) chicken cells. All viral RNAs tested hybridized little with Japanese quail DNA (2 to 5%), turkey DNA (2 to 4%), or duck DNA (1%). DNA from normal chicken cells contained only 60 to 70% of the RAV-60 genetic information, and normal pheasant cells lacked some RAV-61 DNA sequences. RAV-60 and RAV-61 genomes were more homologous to the RAV-0 genome than to the genome of RAV-2, AMV, or B-77(s). RAV-60 and RAV-61 appear to be recombinants between endogenous and exogenous viruses."} {"id": "PMID:172656", "title": "Replication of picornaviruses. I. Evidence from in vitro RNA synthesis that poly(A) of the poliovirus genome is genetically coded.", "content": "A crude replication complex has been isolated from poliovirus-infected HeLa cells and used for synthesis of poliovirus replicative intermediate (RI) RNA, replicative form (RF) RNA, and single-stranded (SS) RNA in vitro. All three classes of virus-specific RNA synthesized in vitro are shown to contain poly(A). Poly(A) of RF and of SS RNA [RF-poly(A) and SS-poly(A)] has a chain length (50 to 70 nucleotides) that is shorter than that of poly(A) of in vivo-synthesized RNAs. Poly(A) of RI [RI-poly(A),] however, is at least 200 nucleotides long and, therefore, larger than poly(A) of RI isolated from HeLa cells 4 h after infection. The crude membrane-bound replication complex contains a terminal adenylate transferase activity that is stimulated by Mn2+ and the addition of an (Ap)2AOH primer. This transferase activity is found also in extracts of mock-infected cells. Partial purificaiton of the replication complex in a stepwise sucrose gradient, in which the viral replicase is associated with the smooth cytoplasmic membrane fraction, does not remove the terminal transferase. However, when the partially purified replication complex is treated with deoxycholate and sedimented through a sucrose gradient, a soluble replication complex can be isolated that is free from terminal adenylate transferase. This soluble replication complex was found to synthesize viral RNA-linked poly(A) longer in chain length than that synthesized by the crude replication complex. Taking into account the 5'-terminal poly(U) in poliovirus minus strands, our data suggest that polyadenylation of poliovirus RNA occurs by transcription and not by end addition. When compared to other viral systems, poliovirus and, probably, all picornaviruses appear to be unique in that the poly(A) of their genome is genetically coded.", "contents": "Replication of picornaviruses. I. Evidence from in vitro RNA synthesis that poly(A) of the poliovirus genome is genetically coded. A crude replication complex has been isolated from poliovirus-infected HeLa cells and used for synthesis of poliovirus replicative intermediate (RI) RNA, replicative form (RF) RNA, and single-stranded (SS) RNA in vitro. All three classes of virus-specific RNA synthesized in vitro are shown to contain poly(A). Poly(A) of RF and of SS RNA [RF-poly(A) and SS-poly(A)] has a chain length (50 to 70 nucleotides) that is shorter than that of poly(A) of in vivo-synthesized RNAs. Poly(A) of RI [RI-poly(A),] however, is at least 200 nucleotides long and, therefore, larger than poly(A) of RI isolated from HeLa cells 4 h after infection. The crude membrane-bound replication complex contains a terminal adenylate transferase activity that is stimulated by Mn2+ and the addition of an (Ap)2AOH primer. This transferase activity is found also in extracts of mock-infected cells. Partial purificaiton of the replication complex in a stepwise sucrose gradient, in which the viral replicase is associated with the smooth cytoplasmic membrane fraction, does not remove the terminal transferase. However, when the partially purified replication complex is treated with deoxycholate and sedimented through a sucrose gradient, a soluble replication complex can be isolated that is free from terminal adenylate transferase. This soluble replication complex was found to synthesize viral RNA-linked poly(A) longer in chain length than that synthesized by the crude replication complex. Taking into account the 5'-terminal poly(U) in poliovirus minus strands, our data suggest that polyadenylation of poliovirus RNA occurs by transcription and not by end addition. When compared to other viral systems, poliovirus and, probably, all picornaviruses appear to be unique in that the poly(A) of their genome is genetically coded."} {"id": "PMID:172657", "title": "Human cytomegalovirus. IV. Specific inhibition of virus-induced DNA polymerase activity and viral DNA replication by phosphonoacetic acid.", "content": "Phosphonoacetic acid specifically inhibited human cytomegalovirus DNA synthesis in virus-infected human fibroblasts as detected by virus-specific nucleic acid hybridization. Inhibition was reversible; viral DNA synthesis resumed upon the removal of the drug. The compound partially inhibited DNA synthesis of host cells in the log phase of growth but had little effect on confluent cells. Studies of partially purified enzymes indicated that phosphonoacetic acid specifically inhibited virus-induced DNA polymerase and had only a slight effect on normal host cell enzymes. The drug was shown to interact directly with virus-induced enzyme but not with the template-primers.", "contents": "Human cytomegalovirus. IV. Specific inhibition of virus-induced DNA polymerase activity and viral DNA replication by phosphonoacetic acid. Phosphonoacetic acid specifically inhibited human cytomegalovirus DNA synthesis in virus-infected human fibroblasts as detected by virus-specific nucleic acid hybridization. Inhibition was reversible; viral DNA synthesis resumed upon the removal of the drug. The compound partially inhibited DNA synthesis of host cells in the log phase of growth but had little effect on confluent cells. Studies of partially purified enzymes indicated that phosphonoacetic acid specifically inhibited virus-induced DNA polymerase and had only a slight effect on normal host cell enzymes. The drug was shown to interact directly with virus-induced enzyme but not with the template-primers."} {"id": "PMID:172658", "title": "Synthesis of herpes simplex virus, vaccinia virus, and adenovirus DNA in isolated HeLa cell nuclei. I. Effect of viral-specific antisera and phosphonoacetic acid.", "content": "Purified nuclei, isolated from appropriately infected HeLa cells, are shown to synthesize large amounts of either herpes simplex virus (HSV) or vaccinia virus DNA in vitro. The rate of synthesis of DNA by nuclei from infected cells is up to 30 times higher than the synthesis of host DNA in vitro by nuclei isolated from uninfected HeLa cells. Thus HSV nuclei obtained from HSV-infected cells make DNA in vitro at a rate comparable to that seen in the intact, infected cell. Molecular hybridization studies showed that 80% of the DNA sequences synthesized in vitro by nuclei from herpesvirus-infected cells are herpesvirus specific. Vaccinia virus nuclei from vaccinia virus-infected cells, also produce comparable percentages of vaccinia virus-specific DNA sequences. Adenovirus nuclei from adenovirus 2-infected HeLa cells, which also synthesize viral DNA in vitro, have been included in this study. Synthesis of DNA by HSV or vaccinia virus nuclei is markedly inhibited by the corresponding viral-specific antisera. These antisera inhibit in a similar fashion the purified herpesvirus-induced or vaccinia virus-induced DNA polymerase isolated from infected cells. Phosphonoacetic acid, reported to be a specific inhibitor of herpesvirus formation and the herpesvirus-induced DNA polymerase, is equally effective as an inhibitor of HSV DNA synthesis in isolated nuclei in vitro. However, we also find phosphonoacetic acid to be an effective inhibitor of vaccinia virus nuclear DNA synthesis and the purified vaccinia virus-induced DNA polymerase. In addition, this compound shows significant inhibition of DNA synthesis in isolated nuclei obtained from adenovirus-infected or uninfected cells and is a potent inhibitor of HeLa cell DNA polymerase alpha.", "contents": "Synthesis of herpes simplex virus, vaccinia virus, and adenovirus DNA in isolated HeLa cell nuclei. I. Effect of viral-specific antisera and phosphonoacetic acid. Purified nuclei, isolated from appropriately infected HeLa cells, are shown to synthesize large amounts of either herpes simplex virus (HSV) or vaccinia virus DNA in vitro. The rate of synthesis of DNA by nuclei from infected cells is up to 30 times higher than the synthesis of host DNA in vitro by nuclei isolated from uninfected HeLa cells. Thus HSV nuclei obtained from HSV-infected cells make DNA in vitro at a rate comparable to that seen in the intact, infected cell. Molecular hybridization studies showed that 80% of the DNA sequences synthesized in vitro by nuclei from herpesvirus-infected cells are herpesvirus specific. Vaccinia virus nuclei from vaccinia virus-infected cells, also produce comparable percentages of vaccinia virus-specific DNA sequences. Adenovirus nuclei from adenovirus 2-infected HeLa cells, which also synthesize viral DNA in vitro, have been included in this study. Synthesis of DNA by HSV or vaccinia virus nuclei is markedly inhibited by the corresponding viral-specific antisera. These antisera inhibit in a similar fashion the purified herpesvirus-induced or vaccinia virus-induced DNA polymerase isolated from infected cells. Phosphonoacetic acid, reported to be a specific inhibitor of herpesvirus formation and the herpesvirus-induced DNA polymerase, is equally effective as an inhibitor of HSV DNA synthesis in isolated nuclei in vitro. However, we also find phosphonoacetic acid to be an effective inhibitor of vaccinia virus nuclear DNA synthesis and the purified vaccinia virus-induced DNA polymerase. In addition, this compound shows significant inhibition of DNA synthesis in isolated nuclei obtained from adenovirus-infected or uninfected cells and is a potent inhibitor of HeLa cell DNA polymerase alpha."} {"id": "PMID:172659", "title": "Effect of the Fv-1 locus on the titration of murine leukemia viruses.", "content": "Titration of N- and B-tropic murine leukemia viruses on sensitive and resistant cell lines has been studied by direct XC plaque assay and infective center assay. The titration of cloned B-tropic virus by infective center assay on BALB/3T3 (Fv-1b/b) and NIH/3T3 (Fv-1n/n) cells gave one-hit patterns, with 100-fold less infected NIH/3T3 cells than BALB/3T3 cells. The titration of B-tropic virus on DBA/2 cells (Fv-1n/n) was also a one-hit. The titration of a one-hit curve, and there were about 100-fold less infected BALB/3T3 cells than NIH/3T3 cells. Comparable results were obtained by titrating the cloned N-tropic virus on congenic SIM (Fv-1n/n) and SIM.R (Fv-1b/b) cells or the Gross N-tropic virus on BALB/3T3 cells. Therefore, our data indicate that the multiple-hit phenomenon described previously may not be an essential part of the Fv-1 gene restriction.", "contents": "Effect of the Fv-1 locus on the titration of murine leukemia viruses. Titration of N- and B-tropic murine leukemia viruses on sensitive and resistant cell lines has been studied by direct XC plaque assay and infective center assay. The titration of cloned B-tropic virus by infective center assay on BALB/3T3 (Fv-1b/b) and NIH/3T3 (Fv-1n/n) cells gave one-hit patterns, with 100-fold less infected NIH/3T3 cells than BALB/3T3 cells. The titration of B-tropic virus on DBA/2 cells (Fv-1n/n) was also a one-hit. The titration of a one-hit curve, and there were about 100-fold less infected BALB/3T3 cells than NIH/3T3 cells. Comparable results were obtained by titrating the cloned N-tropic virus on congenic SIM (Fv-1n/n) and SIM.R (Fv-1b/b) cells or the Gross N-tropic virus on BALB/3T3 cells. Therefore, our data indicate that the multiple-hit phenomenon described previously may not be an essential part of the Fv-1 gene restriction."} {"id": "PMID:172660", "title": "tRNA's associated with the 70S RNA of avian myeloblastosis virus.", "content": "The distribtuion of various amino acid tRNA's in the 4S RNA components of avian myeloblastosis virus (AMV) and in 4S RNA prepared from chicken cmbryo cells, chicken myeloblasts, and chicken livers was determined. This was done by aminoacylating the 4S RNA samples with a mixture of 17 radioactive amino acids and subsequently identifying the tRNA-accepted amino acids on an amino acid analyzer after deacylation. In embryo cells, myeloblasts, and liver, tRNA's accepting all 1m amino acids were demonstrated. \"Free\" AMV 4S RNA was characterized by very low quantities of glutamate, valine, and tyrosine tRNA's. RNAs accepting all 17 amino acids, with the exception of tyrosine, were shown to be present in the \"70S-associated\" 4S RNA which dissociates at 60 C. The bulk of the 70S-associated 4S RNA was dissociated at 60 C at low ionic strength with a concomitant conversion of 70S RNA to 35S RNA. The residual associated 4S RNA was dissociated by further heating of the 35S RNA to 80 C; tryptophan tRNA accounted for greater than 90% of the total amino acid accepting activity in this fraction. The results support other studies in suggesting that tryptophan tRNA may serve as a primer for DNA synthesis in AMV, as has been shown in Rous sarcoma virus.", "contents": "tRNA's associated with the 70S RNA of avian myeloblastosis virus. The distribtuion of various amino acid tRNA's in the 4S RNA components of avian myeloblastosis virus (AMV) and in 4S RNA prepared from chicken cmbryo cells, chicken myeloblasts, and chicken livers was determined. This was done by aminoacylating the 4S RNA samples with a mixture of 17 radioactive amino acids and subsequently identifying the tRNA-accepted amino acids on an amino acid analyzer after deacylation. In embryo cells, myeloblasts, and liver, tRNA's accepting all 1m amino acids were demonstrated. \"Free\" AMV 4S RNA was characterized by very low quantities of glutamate, valine, and tyrosine tRNA's. RNAs accepting all 17 amino acids, with the exception of tyrosine, were shown to be present in the \"70S-associated\" 4S RNA which dissociates at 60 C. The bulk of the 70S-associated 4S RNA was dissociated at 60 C at low ionic strength with a concomitant conversion of 70S RNA to 35S RNA. The residual associated 4S RNA was dissociated by further heating of the 35S RNA to 80 C; tryptophan tRNA accounted for greater than 90% of the total amino acid accepting activity in this fraction. The results support other studies in suggesting that tryptophan tRNA may serve as a primer for DNA synthesis in AMV, as has been shown in Rous sarcoma virus."} {"id": "PMID:172661", "title": "Block to multiplication of adenovirus serotype 2 in monkey cells.", "content": "The block to adenovirus 2 (Ad2) multiplication in monkey cells can be overcome by coinfection with simian virus 40 (SV40). To identify this block we have compared the synthesis of Ad2 proteins in monkey cells infected with Ad2 alone (unenhanced) or with Ad2 plus SV40 (enhanced). Synthesis of viral proteins in enhanced cells was virtually identical to that found for permissive infection of human cells by Ad2 alone. In contrast, the unenhanced cells were strikingly deficient in the production of the IV (fiber) and 11.5K proteins whereas the synthesis of 100K and IVa2 was normal. Synthesis of a number of other proteins such as II, V, and P-VII was partially reduced. A similar specific reduction in synthesis of these proteins was found when their messages were assayed by cell-free translation. This result suggests that the block to Ad2 protein synthesis is at the RNA level rather than with the translational machinery of monkey cells. Analysis of the complexity and the concentration of Ak2-specific RNAs, using hybridization of restriction endonuclease fragments of the Ad2 genome to increasing concentrations of RNA, shows that although all species of late Ad2 mRNA are present, the concentration of several species is reduced sevenfold or more in unenhanced monkey cells as compared with enhanced cells. These species come from regions of the genome known to encode the deficient proteins. A model for the failure of adenovirus to multiply in monkey cells, based on abnormal processing of specific adenovirus messages, is presented.", "contents": "Block to multiplication of adenovirus serotype 2 in monkey cells. The block to adenovirus 2 (Ad2) multiplication in monkey cells can be overcome by coinfection with simian virus 40 (SV40). To identify this block we have compared the synthesis of Ad2 proteins in monkey cells infected with Ad2 alone (unenhanced) or with Ad2 plus SV40 (enhanced). Synthesis of viral proteins in enhanced cells was virtually identical to that found for permissive infection of human cells by Ad2 alone. In contrast, the unenhanced cells were strikingly deficient in the production of the IV (fiber) and 11.5K proteins whereas the synthesis of 100K and IVa2 was normal. Synthesis of a number of other proteins such as II, V, and P-VII was partially reduced. A similar specific reduction in synthesis of these proteins was found when their messages were assayed by cell-free translation. This result suggests that the block to Ad2 protein synthesis is at the RNA level rather than with the translational machinery of monkey cells. Analysis of the complexity and the concentration of Ak2-specific RNAs, using hybridization of restriction endonuclease fragments of the Ad2 genome to increasing concentrations of RNA, shows that although all species of late Ad2 mRNA are present, the concentration of several species is reduced sevenfold or more in unenhanced monkey cells as compared with enhanced cells. These species come from regions of the genome known to encode the deficient proteins. A model for the failure of adenovirus to multiply in monkey cells, based on abnormal processing of specific adenovirus messages, is presented."} {"id": "PMID:172663", "title": "Hepatitis in skunks caused by the virus of infectious canine hepatitis.", "content": "Two cases of acute, fatal, hepatitis occurred in young, striped skunks (Mephitis mephitis) trapped in southern Ontario. Histologically, lesions in the liver were similar to infectious canine hepatitis. A virus was isolated which produced large intranuclear inclusions in dog kidney cell cultures. These inclusions were Feulgen-positive and fluoresced green with acridine orange stain. The skunk hepatitis isolate was identified as the virus of infectious canine hepatitis by virus neutralization tests.", "contents": "Hepatitis in skunks caused by the virus of infectious canine hepatitis. Two cases of acute, fatal, hepatitis occurred in young, striped skunks (Mephitis mephitis) trapped in southern Ontario. Histologically, lesions in the liver were similar to infectious canine hepatitis. A virus was isolated which produced large intranuclear inclusions in dog kidney cell cultures. These inclusions were Feulgen-positive and fluoresced green with acridine orange stain. The skunk hepatitis isolate was identified as the virus of infectious canine hepatitis by virus neutralization tests."} {"id": "PMID:172678", "title": "Histopathological observations of spontaneous regression of Rous sarcomas in Japanese quails.", "content": "Turmors induced in Japanese quails by the Schmidt-Ruppin strain of Rous sarcoma virus were examined histopathologically. The following three phases were recognized in the quails whose tumors regressed finally (regressor). Phase I was between days 4 and 7 of virus inoculation, when growth of tumor cells was seen with predominant infiltration of heterophils. Phase II, from days 10 to 14, was characterized by necrosis of tumor cells and focal accumulation of lymphoid cells which frequently formed follicle-like nodules. In phase III from days 18 to 24, tumor cells and heterophils disappeared, whereas diffuse infilitration of lymphoid cells, plasma cells and histiocytes were demonstrated. In the quails whose tumors progressed (progressor), growth of tumor cells and infiltration of heterophils at phase I seemed to follow a pattern similar to that of regressors, but subsequent infiltration and focal accumulation of lymphoid cells were rare. These morphological findings suggested an immunological reaction against tumor cells by lymphoid cells.", "contents": "Histopathological observations of spontaneous regression of Rous sarcomas in Japanese quails. Turmors induced in Japanese quails by the Schmidt-Ruppin strain of Rous sarcoma virus were examined histopathologically. The following three phases were recognized in the quails whose tumors regressed finally (regressor). Phase I was between days 4 and 7 of virus inoculation, when growth of tumor cells was seen with predominant infiltration of heterophils. Phase II, from days 10 to 14, was characterized by necrosis of tumor cells and focal accumulation of lymphoid cells which frequently formed follicle-like nodules. In phase III from days 18 to 24, tumor cells and heterophils disappeared, whereas diffuse infilitration of lymphoid cells, plasma cells and histiocytes were demonstrated. In the quails whose tumors progressed (progressor), growth of tumor cells and infiltration of heterophils at phase I seemed to follow a pattern similar to that of regressors, but subsequent infiltration and focal accumulation of lymphoid cells were rare. These morphological findings suggested an immunological reaction against tumor cells by lymphoid cells."} {"id": "PMID:172679", "title": "Characterization of \"Pasteurella\" piscicida isolated from white perch and cultivated yellowtail.", "content": "The morphological, physiological, and biochemical characteristics of twelve \"Pasteurella\" piscicida strains isolated from white perch and yellowtail are described and the present uncertain taxonomic status of the organisms is discussed. The organisms isolated were gram-negative rods showing bipolar staining and pleomorphism. No spores or flagella were observed. They were non motile and viscid colonies were formed. Growth was observed in a temperature range of 20 to 30 C and the salinity range of growth was between 0.5% and 4.0%. They were aerobic and facultative anaerobic. Oxidase and catalase were produced. Nitrates were not reduced to nitrites. Lysine and ornithine decarboxylases were not produced but arginine dihydrolase was produced. The egg yolk reaction was positive. Tween 80 and tributyrin were decomposed. Phosphatase was produced. Beta hemolysis was revealed on a medium containing defibrinated blood from chickens or carp but not from mammals. Methyl red and Voges-Proskauer tests were positive, and acetoin was produced from 2,3-butanediol. Glucose was fermented without gas production. Acid was produced from fructose, mannose, galactose, sucrose, maltose, dextrin and glycerol. These organisms differed from all other members of the genus Pasteurella with respect to nitrate reduction, arginine dihydrolase, Voges-Proskauer and methyl red tests. The formation of viscid colonies and inability to grow in a medium without sodium chloride or at 37 C were additional characteristics of these organisms.", "contents": "Characterization of \"Pasteurella\" piscicida isolated from white perch and cultivated yellowtail. The morphological, physiological, and biochemical characteristics of twelve \"Pasteurella\" piscicida strains isolated from white perch and yellowtail are described and the present uncertain taxonomic status of the organisms is discussed. The organisms isolated were gram-negative rods showing bipolar staining and pleomorphism. No spores or flagella were observed. They were non motile and viscid colonies were formed. Growth was observed in a temperature range of 20 to 30 C and the salinity range of growth was between 0.5% and 4.0%. They were aerobic and facultative anaerobic. Oxidase and catalase were produced. Nitrates were not reduced to nitrites. Lysine and ornithine decarboxylases were not produced but arginine dihydrolase was produced. The egg yolk reaction was positive. Tween 80 and tributyrin were decomposed. Phosphatase was produced. Beta hemolysis was revealed on a medium containing defibrinated blood from chickens or carp but not from mammals. Methyl red and Voges-Proskauer tests were positive, and acetoin was produced from 2,3-butanediol. Glucose was fermented without gas production. Acid was produced from fructose, mannose, galactose, sucrose, maltose, dextrin and glycerol. These organisms differed from all other members of the genus Pasteurella with respect to nitrate reduction, arginine dihydrolase, Voges-Proskauer and methyl red tests. The formation of viscid colonies and inability to grow in a medium without sodium chloride or at 37 C were additional characteristics of these organisms."} {"id": "PMID:172691", "title": "Control of plasma aldosterone in normal man during upright posture.", "content": "Plasma aldosterone, plasma renin activity (PRA), plasma cortisol as parameter of ACTH activity and the serum concentrations of sodium and potassium were determined at short time intervals in 10 healthy students after an overnight bedrest and during three hours of ambulation. While PRA rose significantly within 15 minutes of orthostasis in all students, plasma aldosterone showed a similar rapid increase in some of the subjects only. These persons demonstrated also a simultaneous increase of serum potassium or of plasma cortisol. Plasma aldosterone rose not before 30 to 60 minutes after change to the upright position in subjects who showed neigher plasma cortisol nor serum potassium increases. It is concluded that the immediate rise of plasma aldosterone during orthostasis seems to depend on a stimulation by ACTH of by potassium. The main stimulus of plasma aldosterone during orthostasis appears to be the renin angiotensin system. If the aldosterone response to posture is mediated only through this system a delay of 30 to 60 minutes is observed.", "contents": "Control of plasma aldosterone in normal man during upright posture. Plasma aldosterone, plasma renin activity (PRA), plasma cortisol as parameter of ACTH activity and the serum concentrations of sodium and potassium were determined at short time intervals in 10 healthy students after an overnight bedrest and during three hours of ambulation. While PRA rose significantly within 15 minutes of orthostasis in all students, plasma aldosterone showed a similar rapid increase in some of the subjects only. These persons demonstrated also a simultaneous increase of serum potassium or of plasma cortisol. Plasma aldosterone rose not before 30 to 60 minutes after change to the upright position in subjects who showed neigher plasma cortisol nor serum potassium increases. It is concluded that the immediate rise of plasma aldosterone during orthostasis seems to depend on a stimulation by ACTH of by potassium. The main stimulus of plasma aldosterone during orthostasis appears to be the renin angiotensin system. If the aldosterone response to posture is mediated only through this system a delay of 30 to 60 minutes is observed."} {"id": "PMID:172734", "title": "Ultrastructure and virus particles of L1210/Mes. A hamster-adapted murine leukemia.", "content": "The ultrastructural features and virus particle content of L1210/Mes., the hamster-adapted strain of murine leukemia L1210, has been studied in cheek pouch tumors and cell cultures. In comparison with the parental murine tumor in culture, L1210/Mes. has experienced certain morphologic alterations, such as a striking increase in cell size, enlarged and more bizarre nuclei, and an increase in the number of lysosome-related structures. Type A (intracytoplasmic and intracisternal) and type C virus particles could be demonstrated in cell cultures of murine leukemia L1210, and in cheek pouch grafts and cell cultures of L1210/Mes. No. \"H\" (or \"R\") hamster-associated virus particles, however, could be distinguished in L1210/Mes. tumors or in vitro cultivated cells. It appears that a murine lymphoma capable of serial propagation in a xenogeneic host permits the replication of virus particles structurally indistinguishable from those indigenous to it.", "contents": "Ultrastructure and virus particles of L1210/Mes. A hamster-adapted murine leukemia. The ultrastructural features and virus particle content of L1210/Mes., the hamster-adapted strain of murine leukemia L1210, has been studied in cheek pouch tumors and cell cultures. In comparison with the parental murine tumor in culture, L1210/Mes. has experienced certain morphologic alterations, such as a striking increase in cell size, enlarged and more bizarre nuclei, and an increase in the number of lysosome-related structures. Type A (intracytoplasmic and intracisternal) and type C virus particles could be demonstrated in cell cultures of murine leukemia L1210, and in cheek pouch grafts and cell cultures of L1210/Mes. No. \"H\" (or \"R\") hamster-associated virus particles, however, could be distinguished in L1210/Mes. tumors or in vitro cultivated cells. It appears that a murine lymphoma capable of serial propagation in a xenogeneic host permits the replication of virus particles structurally indistinguishable from those indigenous to it."} {"id": "PMID:172735", "title": "Electron paramagnetic resonance and nanosecond fluorescence depolarization studies on creatine-phosphokinase interaction with myosin and its fragments.", "content": "Recent reports in the literature have indicated a physical association of creatine-phosphokinase (CPK) with the tail portion of the myosin molecule. The present paper describes further studies on the interaction of CPK with myosin and myosin fragments, using the techniques of electron paramagnetic resonance (EPR) and nanosecond fluorescence depolarization. From EPR work, spin-labeled CPK appears to interact with myosin, tail-less myosin (heavy meromyosin [HMM]), and myosin heads (subfragment-1 [S1]), the extent of interaction being proportional to the S1 content of myosin or its fragments. Spin-labeled CPK did not evidence interaction with the headless myosin \"rods,\" with myosin tails (light meromyosin [LMM]), with S2 necks (which connect S1 to the rest of the myosin molecule), or with actin. When a fluorescent dye is directed to the essential epsilon-amino group of CPK, nanosecond fluorescence depolarization studies indicate a substantial interaction with myosin, HMM, and S1, but very little with F-actin. When the \"fast-reacting\" thiol of the S1 moiety or the \"essential thiol\" of CPK was labeled with either a fluorescent dye or a spin label, no interaction between CPK and myosin (or S1) was detected.", "contents": "Electron paramagnetic resonance and nanosecond fluorescence depolarization studies on creatine-phosphokinase interaction with myosin and its fragments. Recent reports in the literature have indicated a physical association of creatine-phosphokinase (CPK) with the tail portion of the myosin molecule. The present paper describes further studies on the interaction of CPK with myosin and myosin fragments, using the techniques of electron paramagnetic resonance (EPR) and nanosecond fluorescence depolarization. From EPR work, spin-labeled CPK appears to interact with myosin, tail-less myosin (heavy meromyosin [HMM]), and myosin heads (subfragment-1 [S1]), the extent of interaction being proportional to the S1 content of myosin or its fragments. Spin-labeled CPK did not evidence interaction with the headless myosin \"rods,\" with myosin tails (light meromyosin [LMM]), with S2 necks (which connect S1 to the rest of the myosin molecule), or with actin. When a fluorescent dye is directed to the essential epsilon-amino group of CPK, nanosecond fluorescence depolarization studies indicate a substantial interaction with myosin, HMM, and S1, but very little with F-actin. When the \"fast-reacting\" thiol of the S1 moiety or the \"essential thiol\" of CPK was labeled with either a fluorescent dye or a spin label, no interaction between CPK and myosin (or S1) was detected."} {"id": "PMID:172736", "title": "Birefringence changes in vertebrate striated muscle.", "content": "The changes in birefringence in the rigor to relax transition of single Triton-extracted rabbit psoas muscle fibers have been investigated. The total birefringence of rigor muscle fibers was dependent on sarcomere length and ranged from (1.46 +/- 0.08) X 10(-3) to (1.60 +/- 0.06) X 10(-3) at sarcomere lengths from 2.70 mum to 3.40 mum. An increase in total birefringence was measured dependent on sarcomere length when 55 single fibers were relaxed from the rigor state with Mg-ATP. Pyrophosphate relaxation produced a smaller increase in retardation when compared to Mg-ATP. The expected change in intrinsic birefringence during the rigor to relax transition was calculated assuming a hinge function of the subfragment 2 moiety of myosin. The changes in birefringence during isometric contraction and relaxation have been discussed in relation to possible structural changes.", "contents": "Birefringence changes in vertebrate striated muscle. The changes in birefringence in the rigor to relax transition of single Triton-extracted rabbit psoas muscle fibers have been investigated. The total birefringence of rigor muscle fibers was dependent on sarcomere length and ranged from (1.46 +/- 0.08) X 10(-3) to (1.60 +/- 0.06) X 10(-3) at sarcomere lengths from 2.70 mum to 3.40 mum. An increase in total birefringence was measured dependent on sarcomere length when 55 single fibers were relaxed from the rigor state with Mg-ATP. Pyrophosphate relaxation produced a smaller increase in retardation when compared to Mg-ATP. The expected change in intrinsic birefringence during the rigor to relax transition was calculated assuming a hinge function of the subfragment 2 moiety of myosin. The changes in birefringence during isometric contraction and relaxation have been discussed in relation to possible structural changes."} {"id": "PMID:172737", "title": "Transient kinetic and isotopic tracer studies of the myosin adenosine triphosphatase reaction.", "content": "From transient kinetic studies of the Mg2+-dependent adenosine triphosphatase of myosin subfragment 1, prepared from rabbit skeletal muscle, a seven-step mechanism has been proposed. Features of this mechanism include two-step processes for ATP and ADP binding in which the binary complex isomerizes in addition to a rapid nucleotide association step. In the case of ATP a large negative standard free energy change is associated with the isomerization. An overall rate-limiting isomerization of the myosin-product complex prior to product release has been identified. Studies on the mechanism of cleavage of ATP bound to the active site indicate the process is readily reversible and can account for the observation that more than one oxygen of the product phosphate arises from water. This proposal has been substantiated by the finding that the oxygen atoms of the gamma-phosphoryl group of bound ATP also undergo extensive exchange with water.", "contents": "Transient kinetic and isotopic tracer studies of the myosin adenosine triphosphatase reaction. From transient kinetic studies of the Mg2+-dependent adenosine triphosphatase of myosin subfragment 1, prepared from rabbit skeletal muscle, a seven-step mechanism has been proposed. Features of this mechanism include two-step processes for ATP and ADP binding in which the binary complex isomerizes in addition to a rapid nucleotide association step. In the case of ATP a large negative standard free energy change is associated with the isomerization. An overall rate-limiting isomerization of the myosin-product complex prior to product release has been identified. Studies on the mechanism of cleavage of ATP bound to the active site indicate the process is readily reversible and can account for the observation that more than one oxygen of the product phosphate arises from water. This proposal has been substantiated by the finding that the oxygen atoms of the gamma-phosphoryl group of bound ATP also undergo extensive exchange with water."} {"id": "PMID:172738", "title": "Intermediate complex of ATP hydrolysis and synthesis by muscle proteins.", "content": "Myosin catalyzed exchange between 32Pi and ATP in reaction medium during its enzymatic hydrolysis of ATP only by a very small amount. Addition of actin increased to a great extent the rate of incorporation of 32Pi in the presence of Mg. Glycerinated smooth muscle fibers also exhibited the ability to exchange 32Pi and ATP upon the application of external force (repeated stretching and releasing). A schematic mechanism of the action of actin and external force on acceleration of 32Pi incorporation is proposed and the importance of the M-ADP complex for force generation is suggested.", "contents": "Intermediate complex of ATP hydrolysis and synthesis by muscle proteins. Myosin catalyzed exchange between 32Pi and ATP in reaction medium during its enzymatic hydrolysis of ATP only by a very small amount. Addition of actin increased to a great extent the rate of incorporation of 32Pi in the presence of Mg. Glycerinated smooth muscle fibers also exhibited the ability to exchange 32Pi and ATP upon the application of external force (repeated stretching and releasing). A schematic mechanism of the action of actin and external force on acceleration of 32Pi incorporation is proposed and the importance of the M-ADP complex for force generation is suggested."} {"id": "PMID:172739", "title": "The quantitative measurement of rotational motion of the subfragment-1 region of myosin by saturation transfer epr spectroscopy.", "content": "According to current models of muscle contraction (Huxley, H. E., Science 164: 1356-1366 [1969]), motion of flexible myosin crossbridges is essential to the contractile cycle. Using a spin-label analog of iodoacetamide bound to the subfragment No. 1 (S1) region of myosin, we have obtained rotational correlation times (tau 2) for this region of the molecule with the ultimate goal of making quantitative measurements of the motion of the crossbridges under conditions comparable to those in living, contracting muscle. We used the newly developed technique of saturation transfer electron paramagnetic resonance spectroscopy (Hyde, J.S., and Thomas, D.D., Ann. N.Y. Acad Sci. 22:680-692 [1973]), which is uniquely sensitive to rotational motion in the range of 10(-7)-10(-3) sec. Our results indicate that the spin label is rigidly bound to S1 (tau 2 for isolated S1 is 2 X 10(-7) sec) and that the motion of the label reflects the motion of the S1 region of myosin. the value of tau 2 for the S1 segment of myosin is less than twice that for isolated S1, while the molecular weights differ by a factor of 4, indicating flexibility of myosin in agreement with the conclusions of Mendelson et al. (Biochemistry 12:2250-2255 [1973]). Adding F-actin increses tau 2 in either myosin or isolated S1 by a factor of mearly 103, indicating rigid immobilization of S1 by actin. Formation of myosin filaments (at an ionic strength of 0.15 or less) increses tau 2 by a factor of 10-30, depending on the ionic strength, indicating a decrease of the rotational mobility of S1 in these agregates. The remaining motion is at least a factor of 10 faster than would be expected for the filament itself, suggesting motion of the S1 region independent of the filament backbone but slower than in a single molecule. F-actin has a strong immobilizing effect on labeled S1 in myosin filaments (in 0.137 M KC1), but the immobilization is less complete than that observed when F-actin is added to labeled myosin monomers (in 0.5 M KC1). A spin-label analog of maleimide, attached to the SH-2 thiol groups of S1, is immobilized to a much lesser extent by F-actin than is the label on SH-1 groups. The maleimide label also was attached directly to F-actin and was sufficiently immobilized to suggest rigid binding to actin.", "contents": "The quantitative measurement of rotational motion of the subfragment-1 region of myosin by saturation transfer epr spectroscopy. According to current models of muscle contraction (Huxley, H. E., Science 164: 1356-1366 [1969]), motion of flexible myosin crossbridges is essential to the contractile cycle. Using a spin-label analog of iodoacetamide bound to the subfragment No. 1 (S1) region of myosin, we have obtained rotational correlation times (tau 2) for this region of the molecule with the ultimate goal of making quantitative measurements of the motion of the crossbridges under conditions comparable to those in living, contracting muscle. We used the newly developed technique of saturation transfer electron paramagnetic resonance spectroscopy (Hyde, J.S., and Thomas, D.D., Ann. N.Y. Acad Sci. 22:680-692 [1973]), which is uniquely sensitive to rotational motion in the range of 10(-7)-10(-3) sec. Our results indicate that the spin label is rigidly bound to S1 (tau 2 for isolated S1 is 2 X 10(-7) sec) and that the motion of the label reflects the motion of the S1 region of myosin. the value of tau 2 for the S1 segment of myosin is less than twice that for isolated S1, while the molecular weights differ by a factor of 4, indicating flexibility of myosin in agreement with the conclusions of Mendelson et al. (Biochemistry 12:2250-2255 [1973]). Adding F-actin increses tau 2 in either myosin or isolated S1 by a factor of mearly 103, indicating rigid immobilization of S1 by actin. Formation of myosin filaments (at an ionic strength of 0.15 or less) increses tau 2 by a factor of 10-30, depending on the ionic strength, indicating a decrease of the rotational mobility of S1 in these agregates. The remaining motion is at least a factor of 10 faster than would be expected for the filament itself, suggesting motion of the S1 region independent of the filament backbone but slower than in a single molecule. F-actin has a strong immobilizing effect on labeled S1 in myosin filaments (in 0.137 M KC1), but the immobilization is less complete than that observed when F-actin is added to labeled myosin monomers (in 0.5 M KC1). A spin-label analog of maleimide, attached to the SH-2 thiol groups of S1, is immobilized to a much lesser extent by F-actin than is the label on SH-1 groups. The maleimide label also was attached directly to F-actin and was sufficiently immobilized to suggest rigid binding to actin."} {"id": "PMID:172742", "title": "Lymphography in childhood: six years experience with 242 cases.", "content": "From January, 1969 - December, 1974, 242 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97% (440/463) of the sites where it was attempted. No major or permanent complications were encountered, although minor untoward effects might not have been recorded. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 98% (45/46). Nonspecific reactive hyperplasia lymphographic patterns were encountered in 36% of all studies, confirming its high incidence in the pediatric age group. This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting recurrent tumor. The frequent occurrence of nonspecific reactive hyperplasia in the pediatric lymphogram should not be mistaken for evidence of tumor, particularly lymphoma.", "contents": "Lymphography in childhood: six years experience with 242 cases. From January, 1969 - December, 1974, 242 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97% (440/463) of the sites where it was attempted. No major or permanent complications were encountered, although minor untoward effects might not have been recorded. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 98% (45/46). Nonspecific reactive hyperplasia lymphographic patterns were encountered in 36% of all studies, confirming its high incidence in the pediatric age group. This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting recurrent tumor. The frequent occurrence of nonspecific reactive hyperplasia in the pediatric lymphogram should not be mistaken for evidence of tumor, particularly lymphoma."} {"id": "PMID:172743", "title": "Endolymphatic radiotherapy in malignant lymphomas: its potential \"prophylactic\" value in cases with negative lymphograms.", "content": "From 1961 to 1969 426 patients (208 with Hodgkin's disease and 218 with non-Hodgkin's lymphoma) underwent endolympatic radiotherapy with Lipiodol 131I at the National Cancer Institute of Milano. For this study, only those patients with stage I, II, or III disease (with or without systemic symptoms), who were not previously treated, and who had a complete follow-up were reviewed. It appears that while in the cases where there is lymphographic evidence of involved lymph nodes, endolymphatic radiotherapy is not of value, in the cases with apparently negative lymphography, endolymphatic radiotherapy can reduce the incidence of relapse in the inguino-retroperitoneal nodes to a statistically significant degree.", "contents": "Endolymphatic radiotherapy in malignant lymphomas: its potential \"prophylactic\" value in cases with negative lymphograms. From 1961 to 1969 426 patients (208 with Hodgkin's disease and 218 with non-Hodgkin's lymphoma) underwent endolympatic radiotherapy with Lipiodol 131I at the National Cancer Institute of Milano. For this study, only those patients with stage I, II, or III disease (with or without systemic symptoms), who were not previously treated, and who had a complete follow-up were reviewed. It appears that while in the cases where there is lymphographic evidence of involved lymph nodes, endolymphatic radiotherapy is not of value, in the cases with apparently negative lymphography, endolymphatic radiotherapy can reduce the incidence of relapse in the inguino-retroperitoneal nodes to a statistically significant degree."} {"id": "PMID:172744", "title": "Pain. A central inhibitory balance theory.", "content": "Knowledge of the segmental neuronal circuitry for noxious and non-noxious input is a necessary prelude to understanding pain mechanisms. Significant gaps in our understanding of the synaptology of these pathways in the dorsal horn have hindered progress in this area. This report describes the excitatory and inhibitory circuits that supply the marginal neurons of the spinal cord, whose role in nociceptive mechanisms is well established. On the basis of these data, it is proposed that large primary afferents (non-noxious) provide heavy inhibitory input to marginal neurons via gelatinosa cells. Conversely, small primary afferents (nociceptive) provide excitatory input to marginal neurons but relatively little inhibitory feedback to these cells via gelatinosa neurons. The modulation of pain-producing input depends thus on the balance between large-fiber and small-fiber activity via a postsynaptic inhibitory mechanism acting on the nociceptive relay neurons. This theory accounts satisfactorily for the modulation of pain by counterirritation and by various methods of stimulating large-fiber input.", "contents": "Pain. A central inhibitory balance theory. Knowledge of the segmental neuronal circuitry for noxious and non-noxious input is a necessary prelude to understanding pain mechanisms. Significant gaps in our understanding of the synaptology of these pathways in the dorsal horn have hindered progress in this area. This report describes the excitatory and inhibitory circuits that supply the marginal neurons of the spinal cord, whose role in nociceptive mechanisms is well established. On the basis of these data, it is proposed that large primary afferents (non-noxious) provide heavy inhibitory input to marginal neurons via gelatinosa cells. Conversely, small primary afferents (nociceptive) provide excitatory input to marginal neurons but relatively little inhibitory feedback to these cells via gelatinosa neurons. The modulation of pain-producing input depends thus on the balance between large-fiber and small-fiber activity via a postsynaptic inhibitory mechanism acting on the nociceptive relay neurons. This theory accounts satisfactorily for the modulation of pain by counterirritation and by various methods of stimulating large-fiber input."} {"id": "PMID:172747", "title": "[The treatment of inoperable juvenile angiofibromas (author's transl)].", "content": "Demonstrating a case of juvenile angiofibroma penetrating the base of the scull and growing mainly endocranially we refer to Honvan (Fostestrolum) treatment of this kind of tumor. The effect of this treatment can be shown histologically as a distinct sclerosis of the tumor tissue. Even in long term application of this drug only very few side effects are found.", "contents": "[The treatment of inoperable juvenile angiofibromas (author's transl)]. Demonstrating a case of juvenile angiofibroma penetrating the base of the scull and growing mainly endocranially we refer to Honvan (Fostestrolum) treatment of this kind of tumor. The effect of this treatment can be shown histologically as a distinct sclerosis of the tumor tissue. Even in long term application of this drug only very few side effects are found."} {"id": "PMID:172745", "title": "A possible effect of testosterone on the adenosine 3'-5' cyclic monophosphate levels in rat cerebral cortex. A brief note.", "content": "Based on a correlation of serum testosterone levels and cortical cyclic-AMP concentrations in a normal aging population of male CD Fischer rats and a demonstration of decreased cortical cyclic-AMP subsequent to injection of testosterone, it was concluded that a cause and effect relation between hormone concentrations and brain cyclic nucleotide levels is tenable.", "contents": "A possible effect of testosterone on the adenosine 3'-5' cyclic monophosphate levels in rat cerebral cortex. A brief note. Based on a correlation of serum testosterone levels and cortical cyclic-AMP concentrations in a normal aging population of male CD Fischer rats and a demonstration of decreased cortical cyclic-AMP subsequent to injection of testosterone, it was concluded that a cause and effect relation between hormone concentrations and brain cyclic nucleotide levels is tenable."} {"id": "PMID:172757", "title": "Inhibition of hepatic lipogenesis by adenine nucleotides.", "content": "Incubation of liver slices and isolated liver cells with adenosine cyclic-3',5'-monophosphate at concentrations which inhibit lipogenesis was found to expand the pool size of the noncyclic adenine nucleotides in the intact cells of the preparations. This observation led to studies which demonstrated that adenosine and adenosine-5'-monophosphate also inhibited lipogenesis and expanded the adenine nucleotide pool size. It is proposed but not proven that the increase in intracellular nucleotides produced by adenosine-5'-monophosphate, adenosine cyclic-3',5'-monophosphate, and adenosine may have an adverse effect upon the synthesis of fatty acids. Because of the expansion of the adenine nucleotide pool size, high concentrations of adenosine cyclic-3',5'-monophosphate should not be used to investigate the mechanism responsible for hormonal regulation of lipogenesis. As an added complication, exogenous adenosine-5'-monophosphate was found to produce a small but significant increase in the intracellular concentration of adenosine cyclic-3',5'-monophosphate of isolated liver cells. This effect also may be a factor in the inhibition of lipogenesis by adenosine-5'-monophosphate. Low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate were found to inhibit lipogenesis without increasing the intracellular adenine nucleotide content of either liver slices or isolated liver cells. It is concluded that studies on the mechanism of glucagon regulation of lipogenesis should be carried out with glucagon or low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate.", "contents": "Inhibition of hepatic lipogenesis by adenine nucleotides. Incubation of liver slices and isolated liver cells with adenosine cyclic-3',5'-monophosphate at concentrations which inhibit lipogenesis was found to expand the pool size of the noncyclic adenine nucleotides in the intact cells of the preparations. This observation led to studies which demonstrated that adenosine and adenosine-5'-monophosphate also inhibited lipogenesis and expanded the adenine nucleotide pool size. It is proposed but not proven that the increase in intracellular nucleotides produced by adenosine-5'-monophosphate, adenosine cyclic-3',5'-monophosphate, and adenosine may have an adverse effect upon the synthesis of fatty acids. Because of the expansion of the adenine nucleotide pool size, high concentrations of adenosine cyclic-3',5'-monophosphate should not be used to investigate the mechanism responsible for hormonal regulation of lipogenesis. As an added complication, exogenous adenosine-5'-monophosphate was found to produce a small but significant increase in the intracellular concentration of adenosine cyclic-3',5'-monophosphate of isolated liver cells. This effect also may be a factor in the inhibition of lipogenesis by adenosine-5'-monophosphate. Low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate were found to inhibit lipogenesis without increasing the intracellular adenine nucleotide content of either liver slices or isolated liver cells. It is concluded that studies on the mechanism of glucagon regulation of lipogenesis should be carried out with glucagon or low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate."} {"id": "PMID:172761", "title": "Immunoassay of human plasma apolipoprotein B.", "content": "A specific and precise double antibody immunoassay for human plasma apolipoprotein B (apoB) was developed and applied in normolipidemic and hyperlipidemic subjects. The intra-assay coefficient of variation was ca. 9%. The distributions of total apoB and low density lipoprotein (LDL) apoB in a randomly selected, healthy, fasting population (n = 349) was slightly skewed with a mean total apoB of 81 mg/100 ml and LDL apoB of 72 mg/100 ml. The 90th percentile cutoffs for total apoB and LDL apoB were 106 and 97 mg/100 ml, respectively. Regarding total apoB, women showed a statistically significant increase (r = 0.463, p less than 0.001) with age (30-65) and an average annual increment of plasma apoB of 1.1 mg/100 ml. In contrast, men showed only a slight increase of apoB from the 4th to 5th decade, with an average annual increment of 0.7 mg/100 ml (r = 0.201, 0.02 less than p less than 0.05). Similarly, regarding LDL apoB, women showed an increase of 1.0 mg/100 ml/year from the 4th to 7th decade (r = 0.501, p less than 0.001), whereas men's LDL apoB did not increase significantly with age (r = 0.114, 0.2 less than p less than 0.3, for ages 30-49). Six of ten normal young subjects showed essentially no physiological variation in fasting apoB levels over a 10-wk period, whereas four had a variation of ca. 5% or less. LDL apoB represented ca. 90% of the total apoB in normolipidemic and type II plasma samples (86% in type IV samples) but only 68% in type III plasmas (n = 7). The ratios of LDL cholesterol-LDL apoB were similar for the random and hyperlipoproteinemic groups, ranging from a high of 1.8 for type IIa to a low of 1.5 for type IV. The ratio of cholesterol to apoB was significantly elevated (p less than 0.002) in the d less than 1.006 fraction of the type III plasma samples compared to the random and type II groups.", "contents": "Immunoassay of human plasma apolipoprotein B. A specific and precise double antibody immunoassay for human plasma apolipoprotein B (apoB) was developed and applied in normolipidemic and hyperlipidemic subjects. The intra-assay coefficient of variation was ca. 9%. The distributions of total apoB and low density lipoprotein (LDL) apoB in a randomly selected, healthy, fasting population (n = 349) was slightly skewed with a mean total apoB of 81 mg/100 ml and LDL apoB of 72 mg/100 ml. The 90th percentile cutoffs for total apoB and LDL apoB were 106 and 97 mg/100 ml, respectively. Regarding total apoB, women showed a statistically significant increase (r = 0.463, p less than 0.001) with age (30-65) and an average annual increment of plasma apoB of 1.1 mg/100 ml. In contrast, men showed only a slight increase of apoB from the 4th to 5th decade, with an average annual increment of 0.7 mg/100 ml (r = 0.201, 0.02 less than p less than 0.05). Similarly, regarding LDL apoB, women showed an increase of 1.0 mg/100 ml/year from the 4th to 7th decade (r = 0.501, p less than 0.001), whereas men's LDL apoB did not increase significantly with age (r = 0.114, 0.2 less than p less than 0.3, for ages 30-49). Six of ten normal young subjects showed essentially no physiological variation in fasting apoB levels over a 10-wk period, whereas four had a variation of ca. 5% or less. LDL apoB represented ca. 90% of the total apoB in normolipidemic and type II plasma samples (86% in type IV samples) but only 68% in type III plasmas (n = 7). The ratios of LDL cholesterol-LDL apoB were similar for the random and hyperlipoproteinemic groups, ranging from a high of 1.8 for type IIa to a low of 1.5 for type IV. The ratio of cholesterol to apoB was significantly elevated (p less than 0.002) in the d less than 1.006 fraction of the type III plasma samples compared to the random and type II groups."} {"id": "PMID:172762", "title": "Experimental endocrinopathies.", "content": "Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan.", "contents": "Experimental endocrinopathies. Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan."} {"id": "PMID:172768", "title": "[Bronchial asthma. Pathogenetic assumptions - therapeutic guidelines - the significance of synthetic corticotrophin (ACTH) in its treatment (author's transl)].", "content": "The treatment procedure with 121 in-patients suffering from respiratory obstruction is described following a short review of the etiology and pathogenesis of bronchial asthma, and the consequences for treatment resulting therefrom. While patients with chronic bronchitis caused by an emphysema of the lungs were treated primarily with antibiotics, synthetic corticotrophin (Synacthen, Synacthen Depot) and/or cortisone were prescribed in the treatment of 3/4 of the cases involving asthmatics and patients with chronic asthmatoid bronchitis caused by an emphysema. In severe cases ACTH was combined with cortisone. As a result of corticotrophin's direct effect on the bronchial muscles and the mast cells, along with its stimulation of the adrenal cortex, treatment with ACTH has the advantage over the classic cortisone treatment of retaining the functional ability of the adrenal cortex and reducing the amount of cortisone needed. No ACTH-caused side effects were reported. Included are tables containing guidelines for therapy suitable in private practice.", "contents": "[Bronchial asthma. Pathogenetic assumptions - therapeutic guidelines - the significance of synthetic corticotrophin (ACTH) in its treatment (author's transl)]. The treatment procedure with 121 in-patients suffering from respiratory obstruction is described following a short review of the etiology and pathogenesis of bronchial asthma, and the consequences for treatment resulting therefrom. While patients with chronic bronchitis caused by an emphysema of the lungs were treated primarily with antibiotics, synthetic corticotrophin (Synacthen, Synacthen Depot) and/or cortisone were prescribed in the treatment of 3/4 of the cases involving asthmatics and patients with chronic asthmatoid bronchitis caused by an emphysema. In severe cases ACTH was combined with cortisone. As a result of corticotrophin's direct effect on the bronchial muscles and the mast cells, along with its stimulation of the adrenal cortex, treatment with ACTH has the advantage over the classic cortisone treatment of retaining the functional ability of the adrenal cortex and reducing the amount of cortisone needed. No ACTH-caused side effects were reported. Included are tables containing guidelines for therapy suitable in private practice."} {"id": "PMID:172769", "title": "[Respiratory tract infections of viral origin in infants. Examination of 103 serum pairs in autumn and following spring].", "content": "In autumn 1973 und about four months later in spring 1974 blood samples were taken from the same 103 children aged from a few months to five years and coming from different parts of Bavaria. We examined the samples for complement-fixing antibodies against the influenza virus types A, B and C, the parainfluenza virus types 1, 2 and 3, the adenoviruses and the respiratory-syncytial virus, and for neutralising antibodies against the ECHO virus type 25. At the commencement of the investigation the most frequently detected antibodies were those against adenoviruses (66.0%), ECHO virus type 25 (22.3%), influenza virus type A (15.5%) AND THE RESPIRATORY-SYNCYTIAL VIRUS (10.7%). Over autumn and winter in the four month interval between the drawing of blood samples the most frequently observed infections were those caused by the respiratory-syncytial virus (35.9%), the adenoviruses (13.6%) and the influenza viruses A and B (6.8%). By comparing the results of two blood tests from the same individual infections could be recognised more often than would have been the case if comparing the results of two different groups of children examined in autumn and spring.", "contents": "[Respiratory tract infections of viral origin in infants. Examination of 103 serum pairs in autumn and following spring]. In autumn 1973 und about four months later in spring 1974 blood samples were taken from the same 103 children aged from a few months to five years and coming from different parts of Bavaria. We examined the samples for complement-fixing antibodies against the influenza virus types A, B and C, the parainfluenza virus types 1, 2 and 3, the adenoviruses and the respiratory-syncytial virus, and for neutralising antibodies against the ECHO virus type 25. At the commencement of the investigation the most frequently detected antibodies were those against adenoviruses (66.0%), ECHO virus type 25 (22.3%), influenza virus type A (15.5%) AND THE RESPIRATORY-SYNCYTIAL VIRUS (10.7%). Over autumn and winter in the four month interval between the drawing of blood samples the most frequently observed infections were those caused by the respiratory-syncytial virus (35.9%), the adenoviruses (13.6%) and the influenza viruses A and B (6.8%). By comparing the results of two blood tests from the same individual infections could be recognised more often than would have been the case if comparing the results of two different groups of children examined in autumn and spring."} {"id": "PMID:172777", "title": "A mutant of Aspergillus nidulans defective in NAD-linked glutamate dehydrogenase.", "content": "A mutation leading to partial loss of NAD-linked (\"catabolic') glutamate dehydrogenase does not affect the regulation of ammonium-repressible activities in Aspergillus nidulans. This mutation has been used to show that NAD-linked glutamate dehydrogenase does not normally participate in ammonium assimilation. A mutation leading to loss of NADP-linked (\"anabolic') glutamate dehydrogenase has been used to show that NADP-linked glutamate dehydrogenase is not normally involved in glutamate catabolism. Strains defective in either enzyme are useful for determining which amino acids are metabolised via transamination to yield glutamate rather than via deamination to yield ammonium.", "contents": "A mutant of Aspergillus nidulans defective in NAD-linked glutamate dehydrogenase. A mutation leading to partial loss of NAD-linked (\"catabolic') glutamate dehydrogenase does not affect the regulation of ammonium-repressible activities in Aspergillus nidulans. This mutation has been used to show that NAD-linked glutamate dehydrogenase does not normally participate in ammonium assimilation. A mutation leading to loss of NADP-linked (\"anabolic') glutamate dehydrogenase has been used to show that NADP-linked glutamate dehydrogenase is not normally involved in glutamate catabolism. Strains defective in either enzyme are useful for determining which amino acids are metabolised via transamination to yield glutamate rather than via deamination to yield ammonium."} {"id": "PMID:172778", "title": "The effect of triiodothyronine on myocardial protein kinases.", "content": "Rats treated with T3 (triiodothyronine) showed an increased heart weight after 3 days reaching 100% after 3 weeks of treatment compared to untreated controls. Cytosol protein kinases were not significantly different in the T3 treated rats compared to controls. The protein kinase activity of the NHP (nonhistone proteins) increased after 2 hours and doubled after 3 days for each substrate tested. After 1 week of T3 treatment the protein kinase activity returned to the control value and remained at the control level for the remainder of the 3 week experimental period. A study of the distribution of protein kinase activity in the NHP by disc gel electrophoresis showed that there was a difference in the distribution of some peaks in the T3 treated animals compared to the controls. T3 in concentrations from 10(-11) to 10(-3) M had no in vitro effect on the phosvitin kinase activity of NHP and of cytosol.", "contents": "The effect of triiodothyronine on myocardial protein kinases. Rats treated with T3 (triiodothyronine) showed an increased heart weight after 3 days reaching 100% after 3 weeks of treatment compared to untreated controls. Cytosol protein kinases were not significantly different in the T3 treated rats compared to controls. The protein kinase activity of the NHP (nonhistone proteins) increased after 2 hours and doubled after 3 days for each substrate tested. After 1 week of T3 treatment the protein kinase activity returned to the control value and remained at the control level for the remainder of the 3 week experimental period. A study of the distribution of protein kinase activity in the NHP by disc gel electrophoresis showed that there was a difference in the distribution of some peaks in the T3 treated animals compared to the controls. T3 in concentrations from 10(-11) to 10(-3) M had no in vitro effect on the phosvitin kinase activity of NHP and of cytosol."} {"id": "PMID:172779", "title": "The involvement of superoxide anions in the autoxidation of various cofactors of cysteamine-oxygenase.", "content": "The reduction of tetranitroblue tetrazolium with cysteamine, mediated by a number of dyes, elemental sulphur, elemental selenium and selenide, under aerobic conditions, was inhibited to various extent upon addition of superoxide dismutase. A strict parallelism between the ability to produce O2- ions and the property of those compounds to act as cofactors for cysteamine-oxygenase, to yield hypotaurine, has been observed. Based on the fact that the autoxidation of cysteamine also gives rise to O2- formation, though to a minor extent, we propose a mechanism for cysteamine-oxygenase action. This mechanism was derived from the data obtained in the model system studied.", "contents": "The involvement of superoxide anions in the autoxidation of various cofactors of cysteamine-oxygenase. The reduction of tetranitroblue tetrazolium with cysteamine, mediated by a number of dyes, elemental sulphur, elemental selenium and selenide, under aerobic conditions, was inhibited to various extent upon addition of superoxide dismutase. A strict parallelism between the ability to produce O2- ions and the property of those compounds to act as cofactors for cysteamine-oxygenase, to yield hypotaurine, has been observed. Based on the fact that the autoxidation of cysteamine also gives rise to O2- formation, though to a minor extent, we propose a mechanism for cysteamine-oxygenase action. This mechanism was derived from the data obtained in the model system studied."} {"id": "PMID:172780", "title": "Glucocorticoid receptors and lymphocytolysis in normal and neoplastic lymphocytes.", "content": "When cells of the thymus or mouse leukemias P288 and L1210 are exposed in vitro to the potent synthetic glucocorticoid, 3H-Triamcinolone acetonide, the steroid enters the cells passively and binds to macromolecules in the cytoplasm. At 37 degrees C this hormone-receptor complex enters the nucleus and associates with the chromatin. The association with chromatin occurs not only in the corticosteroid-sensitive rat thymocytes and mouse tumors P288 and P1798S but also in the corticosteroid-resistant mouse tumors L1210 and P1798R. An apparent correlation, although not absolute, exists between the content of glucocorticoid-binding macromolecule and the sensitivity of the lymphocytes studied to the lytic effect of glucocorticoids; the sensitive cells having more receptor than the resistant cells. The process of lysis is attributed to the release from the much larger stores of triglyceride in thymus and sensitive lymphoma cells, of a large pool of FFA which causes focal damage to the nuclear membrane resulting in karyorrhexis and, subsequently, to cytolysis. Resistance is attributed to the capacity for preventing the accumulation of greater than about 0.5 fmole FFA/cell. Resistant cells induced to accumulate greater amounts, even for a few minutes, ultimately undergo lysis. Most effective in accomplishing this are branched chain fatty acids of C-8 and higher, which block FFA metabolism, causing accumulation which results in cytolysis.", "contents": "Glucocorticoid receptors and lymphocytolysis in normal and neoplastic lymphocytes. When cells of the thymus or mouse leukemias P288 and L1210 are exposed in vitro to the potent synthetic glucocorticoid, 3H-Triamcinolone acetonide, the steroid enters the cells passively and binds to macromolecules in the cytoplasm. At 37 degrees C this hormone-receptor complex enters the nucleus and associates with the chromatin. The association with chromatin occurs not only in the corticosteroid-sensitive rat thymocytes and mouse tumors P288 and P1798S but also in the corticosteroid-resistant mouse tumors L1210 and P1798R. An apparent correlation, although not absolute, exists between the content of glucocorticoid-binding macromolecule and the sensitivity of the lymphocytes studied to the lytic effect of glucocorticoids; the sensitive cells having more receptor than the resistant cells. The process of lysis is attributed to the release from the much larger stores of triglyceride in thymus and sensitive lymphoma cells, of a large pool of FFA which causes focal damage to the nuclear membrane resulting in karyorrhexis and, subsequently, to cytolysis. Resistance is attributed to the capacity for preventing the accumulation of greater than about 0.5 fmole FFA/cell. Resistant cells induced to accumulate greater amounts, even for a few minutes, ultimately undergo lysis. Most effective in accomplishing this are branched chain fatty acids of C-8 and higher, which block FFA metabolism, causing accumulation which results in cytolysis."} {"id": "PMID:172781", "title": "A directed alteration of ribonuclease specificity. Hydrolysis of polyribonucleotides containing modified cytosine bases.", "content": "The action of ribonucleases on poly and oligoribonucleotides containing cytosine bases modified by methoxyamine and bisulphite was examined. Resistance of phosphodiester bonds in (Cp)nXp (where n greater than or equal to 1 and X stands for A, G or U) to T2 RNase hydrolysis was observed if substrates were modified chemically. The phenomenon formed the basis for isolation of (Cp)nXp blocks as an additional tool in sequence investigations. After modification of cytosine pancreatic RNase was unable to hydrolyse (Cp)nUp blocks. Therefore the specificity of pyrimidyl RNase may be narrowed to 'uridyl RNase'.", "contents": "A directed alteration of ribonuclease specificity. Hydrolysis of polyribonucleotides containing modified cytosine bases. The action of ribonucleases on poly and oligoribonucleotides containing cytosine bases modified by methoxyamine and bisulphite was examined. Resistance of phosphodiester bonds in (Cp)nXp (where n greater than or equal to 1 and X stands for A, G or U) to T2 RNase hydrolysis was observed if substrates were modified chemically. The phenomenon formed the basis for isolation of (Cp)nXp blocks as an additional tool in sequence investigations. After modification of cytosine pancreatic RNase was unable to hydrolyse (Cp)nUp blocks. Therefore the specificity of pyrimidyl RNase may be narrowed to 'uridyl RNase'."} {"id": "PMID:172782", "title": "Influence of a specific histone kinase on the physico-chemical properties of chromatin in situ.", "content": "The influence of a specific histone kinase, phosphorylating lysine-rich histone F1, F2a2, F2b, on the physico-chemical properties of the chromatin in the whole undestroyed fixed cell, has been investigated. It was found that the exogenous histone kinase penetrates into the nuclei of the undestroyed fixed cells and into the isolated unfixed nuclei and changes the physico-chemical properties of the chromatin there, bringing about an increase in binding of a basic dye acridine orange and a decrease in its stability to heat.", "contents": "Influence of a specific histone kinase on the physico-chemical properties of chromatin in situ. The influence of a specific histone kinase, phosphorylating lysine-rich histone F1, F2a2, F2b, on the physico-chemical properties of the chromatin in the whole undestroyed fixed cell, has been investigated. It was found that the exogenous histone kinase penetrates into the nuclei of the undestroyed fixed cells and into the isolated unfixed nuclei and changes the physico-chemical properties of the chromatin there, bringing about an increase in binding of a basic dye acridine orange and a decrease in its stability to heat."} {"id": "PMID:172784", "title": "[Results of non-specific iliac crest biopsy in patients with bronchial carcinoma (author's transl)].", "content": "Systematic bone marrow examinations in patients with bronchial carcinoma (n equals 75) gave positive findings (identification of tumor cells) in 12% related to all types of tumors and in 32% of microcellular carcinoma. The information value of this method is relatively small with regard to the assessment of operability, because positive findings in stages I and II are extremely rare. Non-specific iliac crest biopsy provides therapeutically and prognostically important pointers in patients who are to be irradiated (tumor stage III and all microcellular tumors of stages I-III), because a positive bone marrow finding must be valued as stage IV.", "contents": "[Results of non-specific iliac crest biopsy in patients with bronchial carcinoma (author's transl)]. Systematic bone marrow examinations in patients with bronchial carcinoma (n equals 75) gave positive findings (identification of tumor cells) in 12% related to all types of tumors and in 32% of microcellular carcinoma. The information value of this method is relatively small with regard to the assessment of operability, because positive findings in stages I and II are extremely rare. Non-specific iliac crest biopsy provides therapeutically and prognostically important pointers in patients who are to be irradiated (tumor stage III and all microcellular tumors of stages I-III), because a positive bone marrow finding must be valued as stage IV."} {"id": "PMID:172785", "title": "[Synthetic ACTH in theumatic diseases: (author's transl)].", "content": "44 patients with acute irritations of degenerative articular diseases and 66 patients with soft tissue rheumatism were treated with Synacthen Depot (tetracosactide hexacetate 1 mg/ml). During the first three days of treatment the patients received an average of 2 ampoulbs Synacthen Depot, then treatment was continued at 3-4 day intervals. In the degenerative joint disease group 86.4% and 89.4% in the group with soft tissue rheumatism became free of complaints or improved with the ACTH treatment. Most of the patients with degenerative joint diseases needed a 4 week treatment; 1/3 of the patients with soft tissue rheumatism were already free of complai", "contents": "[Synthetic ACTH in theumatic diseases: (author's transl)]. 44 patients with acute irritations of degenerative articular diseases and 66 patients with soft tissue rheumatism were treated with Synacthen Depot (tetracosactide hexacetate 1 mg/ml). During the first three days of treatment the patients received an average of 2 ampoulbs Synacthen Depot, then treatment was continued at 3-4 day intervals. In the degenerative joint disease group 86.4% and 89.4% in the group with soft tissue rheumatism became free of complaints or improved with the ACTH treatment. Most of the patients with degenerative joint diseases needed a 4 week treatment; 1/3 of the patients with soft tissue rheumatism were already free of complai"} {"id": "PMID:172786", "title": "Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells of mice. I. Relative sensitivity between pre- and postcopulation germ cells to isopropyl methanesulfonate.", "content": "Females from (C3H X 101)F1 and a mixed stock were injected intraperitoneally with either 25 or 50 mg/kg isopropyl methanesulfonate (IMS) or Hanks' solution 4-5 h after the midpoint of the dark period during which mating occurred. It was determined that at the time of treatment the great majority of oocytes were undergoing second meiotic division. For comparison, the same doses of IMS were given to females treated within 3-5 days prior to mating (predominantly dictyate oocytes) or to males treated within 4-5 days prior to mating (sperm in vas and epididymis). The frequencies of presumed dominant lethals induced by 50 mg/kg IMS in sperm treated in vas and epididymis, dictyate oocytes, and germ cells in mated females are 22%, 19%, and 79%, respectively, for (C3H X 101)F1 and 26%, 30%, and 76% for the other stock. Clearly, in both stocks, effects in mated females, when both female and male germ cells were treated, are relatively much higher than the added effects on dyctyate oocytes and spermatozoa. This is also true for the 25 mg/kg dose.", "contents": "Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells of mice. I. Relative sensitivity between pre- and postcopulation germ cells to isopropyl methanesulfonate. Females from (C3H X 101)F1 and a mixed stock were injected intraperitoneally with either 25 or 50 mg/kg isopropyl methanesulfonate (IMS) or Hanks' solution 4-5 h after the midpoint of the dark period during which mating occurred. It was determined that at the time of treatment the great majority of oocytes were undergoing second meiotic division. For comparison, the same doses of IMS were given to females treated within 3-5 days prior to mating (predominantly dictyate oocytes) or to males treated within 4-5 days prior to mating (sperm in vas and epididymis). The frequencies of presumed dominant lethals induced by 50 mg/kg IMS in sperm treated in vas and epididymis, dictyate oocytes, and germ cells in mated females are 22%, 19%, and 79%, respectively, for (C3H X 101)F1 and 26%, 30%, and 76% for the other stock. Clearly, in both stocks, effects in mated females, when both female and male germ cells were treated, are relatively much higher than the added effects on dyctyate oocytes and spermatozoa. This is also true for the 25 mg/kg dose."} {"id": "PMID:172787", "title": "Induction of gene mutations and chromosomal aberrations by simian virus 40 in cultured mammalian cells.", "content": "Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cells. In Chinese hamster cells SV40-induced chromosome aberrations were also studied. SV40 penetrated into the cells of both lines and induced synthesis of the T antigen. The efficiency of infection in Chinese hamster cells was tested additionally by their ability to form colonies in medium lacking the serum growth factor. The maximal number of cells with serum growth factor independence was observed on the first day after infection. When hamster cells had been maintained in \"factor-free medium\" for the first two passages after infection a sub-line was isolated, which synthesized T antigen 60 days after exposure to SV40. This was considered to be an indirect proof of the integration of viral genome into host chromosome. A significant increase in the frequency of chromosomal aberrations was detected in SV40-infected Chinese hamster cells. It was observed on the first and second days after treatment. The most numberous were the chromosome and chromatid breaks, which were distributed randomly in 5 morphological groups according to the chromosome length. SV40-induced mutations of resistance to 8-AG and 6-MP in human and Chinese hamster cells respectively were detected, when cells were plated in selective medium one to five days after infection. Induction was detected in all the 4 experiments with human cells and in 9 out of 11 experiments with Chinese hamster cells. Induction was highly significant according to the Wilcoxon test (P greater than 0.99), when the results of all experiments carried out in human and Chinese hamster cells were summarized. Resistance was stable after prolonged cultivation of 13 isolated clones under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosomal aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogenesis is discussed.", "contents": "Induction of gene mutations and chromosomal aberrations by simian virus 40 in cultured mammalian cells. Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cells. In Chinese hamster cells SV40-induced chromosome aberrations were also studied. SV40 penetrated into the cells of both lines and induced synthesis of the T antigen. The efficiency of infection in Chinese hamster cells was tested additionally by their ability to form colonies in medium lacking the serum growth factor. The maximal number of cells with serum growth factor independence was observed on the first day after infection. When hamster cells had been maintained in \"factor-free medium\" for the first two passages after infection a sub-line was isolated, which synthesized T antigen 60 days after exposure to SV40. This was considered to be an indirect proof of the integration of viral genome into host chromosome. A significant increase in the frequency of chromosomal aberrations was detected in SV40-infected Chinese hamster cells. It was observed on the first and second days after treatment. The most numberous were the chromosome and chromatid breaks, which were distributed randomly in 5 morphological groups according to the chromosome length. SV40-induced mutations of resistance to 8-AG and 6-MP in human and Chinese hamster cells respectively were detected, when cells were plated in selective medium one to five days after infection. Induction was detected in all the 4 experiments with human cells and in 9 out of 11 experiments with Chinese hamster cells. Induction was highly significant according to the Wilcoxon test (P greater than 0.99), when the results of all experiments carried out in human and Chinese hamster cells were summarized. Resistance was stable after prolonged cultivation of 13 isolated clones under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosomal aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogenesis is discussed."} {"id": "PMID:172799", "title": "Molecular structures of cytidine-5'-diphosphate and cytidine-5'-diphospho-choline, and their role in intermidiary metabolism.", "content": "The nucleotide coenzyme cytidine-5'-diphospho-choline is highly folded. The CMP-5' parts of the molecules in the crystal structure are strongly linked by metal ligation and hydrogen bonds leaving the phosphoryl-choline residues relatively free. Cytidine-5'-diphosphoric acid exists as a zwitterion with N31 protonated. The P-O bond lengths from the anhydride bridging oxygen in the pyrophosphate are significantly different.", "contents": "Molecular structures of cytidine-5'-diphosphate and cytidine-5'-diphospho-choline, and their role in intermidiary metabolism. The nucleotide coenzyme cytidine-5'-diphospho-choline is highly folded. The CMP-5' parts of the molecules in the crystal structure are strongly linked by metal ligation and hydrogen bonds leaving the phosphoryl-choline residues relatively free. Cytidine-5'-diphosphoric acid exists as a zwitterion with N31 protonated. The P-O bond lengths from the anhydride bridging oxygen in the pyrophosphate are significantly different."} {"id": "PMID:172803", "title": "Lipoprotein receptors and genetic control of cholesterol metabolism in cultured human cells.", "content": "Biochemical analysis of cultured fibroblasts obtained from human subjects with the autosomal dominant disorder familial hypercholesterolemia has led to the identification of a hitherto unrecognized cell-surface receptor for serum lipoproteins. This receptor plays a critical role in the physiologic regulation of cholesterol metabolism in human cells, and its absence leads to elevation of serum-cholesterol levels and severe atheroslerosis.", "contents": "Lipoprotein receptors and genetic control of cholesterol metabolism in cultured human cells. Biochemical analysis of cultured fibroblasts obtained from human subjects with the autosomal dominant disorder familial hypercholesterolemia has led to the identification of a hitherto unrecognized cell-surface receptor for serum lipoproteins. This receptor plays a critical role in the physiologic regulation of cholesterol metabolism in human cells, and its absence leads to elevation of serum-cholesterol levels and severe atheroslerosis."} {"id": "PMID:172804", "title": "Cyclic AMP-dependent protein kinases and binding sites for cyclic AMP in rat erythrocytes.", "content": "In red cell preparations from reticulocyte-poor (untreated animals; approximately 2% reticulocytes) and reticulocyte-rich blood (animals pretreated with acetylphenylhydrazide; approximately 60% reticulocytes) of rats, cAMP binding sites and cAMP-dependent protein kinase activities were determined. High affinity binding sites for cAMP were present both in membrane and cytoplasmic preparations; while the apparent binding constants determined in both cell fractions (approximately 3 x 10(-9) M for membrane, approximately 2 x 10(-8) M for cytoplasmic fractions) were independent of the reticulocyte content of the preparations, the respective numbers of sites were about twice as high in the reticulocyte-rich as in the reticulocyte-poor preparations. In membrane preparations, significant cAMP-dependent protein kinase activity could be detected only in membrane fractions from reticulocyte-rich blood which were considerably contaminated by intracellular components (\"haemoglobin-containing membranes') while in washed (\"haemoglobin-free') membranes no cAMP-dependent protein kinase activity was found. In cytoplasmic preparations both from reticulocyte-poor and reticulocyte-rich blood, two different protein kinases, a low and a high Ka enzyme, were tentatively differentiated by kinetic data; the apparent activation constant for the high Ka enzyme (approximately less than 5 x 10(-8) M) was in the concentration range of the binding constants determined on cytoplasmic preparations. The activity of the high Ka protein kinase was several fold higher in reticulocyte-rich than in reticulocyte-poor cytoplasmic fractions, while the activity of the low Ka enzyme was obviously independent of the reticulocyte content. From the results obtained, it is concluded that in premature rat erythrocytes, membrane protein(s) may serve as protein substrates for cAMP-dependent protein kinase(s) located in the cytoplasm. This assumption was supported by experiments with intact erythrocytes (prelabelled with inorganic 32P-phosphate) from reticulocyte-rich blood: isoprenaline, theophylline, and also dibutyryl-cAMP significantly increased phosphorylation of membrane protein of these cells. From the results presented (and others previously reported) it becomes evident that only premature rat erythrocytes, i.e. reticulocytes, are equipped with a beta-adrenergic receptor-effector system consisting of a beta-adrenergically stimulated adenyl cyclase and cAMP-dependent protein kinase(s). Obviously, the adrenergic receptor system and also part of the effector system is lost during the process of red cell maturation.", "contents": "Cyclic AMP-dependent protein kinases and binding sites for cyclic AMP in rat erythrocytes. In red cell preparations from reticulocyte-poor (untreated animals; approximately 2% reticulocytes) and reticulocyte-rich blood (animals pretreated with acetylphenylhydrazide; approximately 60% reticulocytes) of rats, cAMP binding sites and cAMP-dependent protein kinase activities were determined. High affinity binding sites for cAMP were present both in membrane and cytoplasmic preparations; while the apparent binding constants determined in both cell fractions (approximately 3 x 10(-9) M for membrane, approximately 2 x 10(-8) M for cytoplasmic fractions) were independent of the reticulocyte content of the preparations, the respective numbers of sites were about twice as high in the reticulocyte-rich as in the reticulocyte-poor preparations. In membrane preparations, significant cAMP-dependent protein kinase activity could be detected only in membrane fractions from reticulocyte-rich blood which were considerably contaminated by intracellular components (\"haemoglobin-containing membranes') while in washed (\"haemoglobin-free') membranes no cAMP-dependent protein kinase activity was found. In cytoplasmic preparations both from reticulocyte-poor and reticulocyte-rich blood, two different protein kinases, a low and a high Ka enzyme, were tentatively differentiated by kinetic data; the apparent activation constant for the high Ka enzyme (approximately less than 5 x 10(-8) M) was in the concentration range of the binding constants determined on cytoplasmic preparations. The activity of the high Ka protein kinase was several fold higher in reticulocyte-rich than in reticulocyte-poor cytoplasmic fractions, while the activity of the low Ka enzyme was obviously independent of the reticulocyte content. From the results obtained, it is concluded that in premature rat erythrocytes, membrane protein(s) may serve as protein substrates for cAMP-dependent protein kinase(s) located in the cytoplasm. This assumption was supported by experiments with intact erythrocytes (prelabelled with inorganic 32P-phosphate) from reticulocyte-rich blood: isoprenaline, theophylline, and also dibutyryl-cAMP significantly increased phosphorylation of membrane protein of these cells. From the results presented (and others previously reported) it becomes evident that only premature rat erythrocytes, i.e. reticulocytes, are equipped with a beta-adrenergic receptor-effector system consisting of a beta-adrenergically stimulated adenyl cyclase and cAMP-dependent protein kinase(s). Obviously, the adrenergic receptor system and also part of the effector system is lost during the process of red cell maturation."} {"id": "PMID:172805", "title": "cAMP as a second messenger in central blood pressure control.", "content": "Injections of dibutyryl cyclic adenosine 3',5'-monophosphate in doses of 125, 250 and 500 mug/kg into the lateral cerebral ventricle of anaesthetised cats produced dose dependent increases in blood pressure and heart rate, while doses of 50, 100 and 200 mug/kg imidazole-4-acetic acid, a stimulator of phosphodiesterase, exerted an opposite effect. The results are discussed in the light of the hypothesis that the activity of cardiovascular centres is determined by their concentration of cyclic AMP.", "contents": "cAMP as a second messenger in central blood pressure control. Injections of dibutyryl cyclic adenosine 3',5'-monophosphate in doses of 125, 250 and 500 mug/kg into the lateral cerebral ventricle of anaesthetised cats produced dose dependent increases in blood pressure and heart rate, while doses of 50, 100 and 200 mug/kg imidazole-4-acetic acid, a stimulator of phosphodiesterase, exerted an opposite effect. The results are discussed in the light of the hypothesis that the activity of cardiovascular centres is determined by their concentration of cyclic AMP."} {"id": "PMID:172806", "title": "Characterisation of the adrenoceptor mediating changes in cyclic adenosine 3'-5' monophosphate in chick cerebral hemispheres.", "content": "Noradrenaline, adrenaline, isoprenaline and salbutamol induced marked accumulations of cyclic AMP in incubated slices of chick cerebral hemispheres. Isoprenaline was both more potent and more powerful than adrenaline or noradrenaline and the increase in cyclic AMP elicited by the catecholamines was powerfully antagonized by the beta-adrenoceptor antagonist propranolol but not by the alphapadrenoceptor blocker phentolamine. The order of potency of the catecholamines isoprenaline greater than adrenaline greater than noradrenaline and the ability of the non-catechol salbutamol to stimulate cyclic AMP accumulation in chick cerebral slices suggests that the beta-adrenoceptro may resemble that found in the lung (beta2) rather than that in the heart (beta1). Propranolol proved to be a very potent antagonist of the cyclic AMP response induced by isoprenaline in vivo. Beta-adrenoceptor blockade was still evident 12 hrs after a single injection of the durg although only negligible amounts of 3H-propranolol could be detected in cerebral tissue after 2 hrs.", "contents": "Characterisation of the adrenoceptor mediating changes in cyclic adenosine 3'-5' monophosphate in chick cerebral hemispheres. Noradrenaline, adrenaline, isoprenaline and salbutamol induced marked accumulations of cyclic AMP in incubated slices of chick cerebral hemispheres. Isoprenaline was both more potent and more powerful than adrenaline or noradrenaline and the increase in cyclic AMP elicited by the catecholamines was powerfully antagonized by the beta-adrenoceptor antagonist propranolol but not by the alphapadrenoceptor blocker phentolamine. The order of potency of the catecholamines isoprenaline greater than adrenaline greater than noradrenaline and the ability of the non-catechol salbutamol to stimulate cyclic AMP accumulation in chick cerebral slices suggests that the beta-adrenoceptro may resemble that found in the lung (beta2) rather than that in the heart (beta1). Propranolol proved to be a very potent antagonist of the cyclic AMP response induced by isoprenaline in vivo. Beta-adrenoceptor blockade was still evident 12 hrs after a single injection of the durg although only negligible amounts of 3H-propranolol could be detected in cerebral tissue after 2 hrs."} {"id": "PMID:172807", "title": "Effects of drugs and axotomy on acetylcholine levels in central cholinergic neurons.", "content": "Administration of cholinergic nuscarinic agonists either did not alter, or increased hippocampal Ach levels, while antagonists lowered the levels. As observed previously, placement of lesions in the medial septal area resulted in a rise in hippocampal Ach levels in the first thirty minutes. Agonist drugs administered immediately before lesion, further increased the post-lesion rise in Ach levels. With antagonists, inconsistent results were obtained in that atropine blocked the post-lesion rise, while scopolamine and quinuclidinyl benzilate (QNB) potentiated the post-lesion rise. These results suggest that there may be receptor-mediated effects on Ach synthesis or release after axotomy.", "contents": "Effects of drugs and axotomy on acetylcholine levels in central cholinergic neurons. Administration of cholinergic nuscarinic agonists either did not alter, or increased hippocampal Ach levels, while antagonists lowered the levels. As observed previously, placement of lesions in the medial septal area resulted in a rise in hippocampal Ach levels in the first thirty minutes. Agonist drugs administered immediately before lesion, further increased the post-lesion rise in Ach levels. With antagonists, inconsistent results were obtained in that atropine blocked the post-lesion rise, while scopolamine and quinuclidinyl benzilate (QNB) potentiated the post-lesion rise. These results suggest that there may be receptor-mediated effects on Ach synthesis or release after axotomy."} {"id": "PMID:172808", "title": "Reactions of 4-halogeno-N,N-dimethylaniline-N-oxide with hemoglobin.", "content": "Incubation with ferrihemoglobin or ferricytochrome c transforms 4-bromo-N,N-dimethylaniline-N-oxide (BrDANO) into 4-bromo-N,N-dimethylaniline, 4-bromo-N-methylaniline, and 2-dimethylamino-5-bromo-phenol. In a secondary reaction 4-bromo-N'-(4-bromophenyl)-6-hydroxy-N,N,N-trimethyl-1,3-phenylenediamine (U) was found from 2-dimethylamino-5-bromo-phenol and 4-bromo-N-methylaniline. The products were isolated and identified, the structure of (U) was elucidated. It has been found that the formation of ferrihemoglobin by BrDANO is an autocatalytic reaction, ferrihemoglobin being the catalyst. BrDANO reacts with the catalyst resulting in the named products. 2-Dimetnylamino-5-bromo-phenol oxidizes hemoglobin in the presence of oxygen. Thereby the catalyst ferrihemoglobin increases, which in turn increases the transformation of BrDANO to ferrihemoglobin forming derivates. This cycyle explains the autocatalytic character of the production of ferrihemoglobulin by BrDANO. The primary products of the reaction between 4-fluoro-N,N-dimethylaniline-N-oxide (FDANO) or 4-chloro-N,N-dimethylaniline-N-oxide (ClDANO) with cytochrome c, 4-fluoro- and 4-chloro-N,N-dimethylaniline, 4-fluoro- and 4-chloro-N-methylaniline, 2-dimethylamino-5-fluoro-phenol, and 2-dimethylamino-5-chloro-phenol were isolated and identified. The reactions between N,N-dimethylaniline-N-oxide (DANO), BrDANO, ClDANO, FDANO, and hemoglobin from blood of various species were studied. BrDano and ClDANO accelerate the formation of ferrihemoglobin in solutions of hemoglobin from beef and dog blood much more effectively than DANO and FDANO.", "contents": "Reactions of 4-halogeno-N,N-dimethylaniline-N-oxide with hemoglobin. Incubation with ferrihemoglobin or ferricytochrome c transforms 4-bromo-N,N-dimethylaniline-N-oxide (BrDANO) into 4-bromo-N,N-dimethylaniline, 4-bromo-N-methylaniline, and 2-dimethylamino-5-bromo-phenol. In a secondary reaction 4-bromo-N'-(4-bromophenyl)-6-hydroxy-N,N,N-trimethyl-1,3-phenylenediamine (U) was found from 2-dimethylamino-5-bromo-phenol and 4-bromo-N-methylaniline. The products were isolated and identified, the structure of (U) was elucidated. It has been found that the formation of ferrihemoglobin by BrDANO is an autocatalytic reaction, ferrihemoglobin being the catalyst. BrDANO reacts with the catalyst resulting in the named products. 2-Dimetnylamino-5-bromo-phenol oxidizes hemoglobin in the presence of oxygen. Thereby the catalyst ferrihemoglobin increases, which in turn increases the transformation of BrDANO to ferrihemoglobin forming derivates. This cycyle explains the autocatalytic character of the production of ferrihemoglobulin by BrDANO. The primary products of the reaction between 4-fluoro-N,N-dimethylaniline-N-oxide (FDANO) or 4-chloro-N,N-dimethylaniline-N-oxide (ClDANO) with cytochrome c, 4-fluoro- and 4-chloro-N,N-dimethylaniline, 4-fluoro- and 4-chloro-N-methylaniline, 2-dimethylamino-5-fluoro-phenol, and 2-dimethylamino-5-chloro-phenol were isolated and identified. The reactions between N,N-dimethylaniline-N-oxide (DANO), BrDANO, ClDANO, FDANO, and hemoglobin from blood of various species were studied. BrDano and ClDANO accelerate the formation of ferrihemoglobin in solutions of hemoglobin from beef and dog blood much more effectively than DANO and FDANO."} {"id": "PMID:172809", "title": "Adrenal cortex adenylate cyclase: solubilization of adenylate cyclase and guanyl nucleotide binding sites.", "content": "Adenylate cyclase activity and binding sites for 5'-guanylyl-imidiphosphate [Cpp(NH)p] have been solubilized from bovine adrenal cortex membranes with Triton N-101. Solubilized adenylate cyclase is stimulated by Gpp(nh)p and fluoride ion but not by ACTH. Pretreatment of particulate membrane fractions with Gpp(NH)p, hormone and Gpp(NH)p or fluoride prior to detergent extraction leads to an activated solubilized enzyme which is nearly independent from added stimulants. Adenylate cyclase solubilized from membranes pretreated with Gpp(NH)p can be separated from guanyl nucleotide binding sites without loss of activity.", "contents": "Adrenal cortex adenylate cyclase: solubilization of adenylate cyclase and guanyl nucleotide binding sites. Adenylate cyclase activity and binding sites for 5'-guanylyl-imidiphosphate [Cpp(NH)p] have been solubilized from bovine adrenal cortex membranes with Triton N-101. Solubilized adenylate cyclase is stimulated by Gpp(nh)p and fluoride ion but not by ACTH. Pretreatment of particulate membrane fractions with Gpp(NH)p, hormone and Gpp(NH)p or fluoride prior to detergent extraction leads to an activated solubilized enzyme which is nearly independent from added stimulants. Adenylate cyclase solubilized from membranes pretreated with Gpp(NH)p can be separated from guanyl nucleotide binding sites without loss of activity."} {"id": "PMID:172810", "title": "Effect of depolarizing agents on the adenosine-3',5'-monophosphate content of the bovine superior cervical ganglion.", "content": "The cAMP content of the bovine superior cervical ganglion increases rapidly when the tissue is incubated in media containing high concentrations of potassium and theophylline. This effect of high K+ is mimicked by Rb+, Cs+ and NH4+. The depolarizing substances veratridine and ouabain also cause an increase in the concentration of ganglionic cAMP; the effect of ouabain develops more slowly than that of veratridine. Tetracaine, in high concentrations, reduces the response to potassium, whereas it reduces the response to veratridine at much lower concentrations. Tetrodotoxin, at a concentration that barely affects the response to potassium, prevents the response to veratridine.", "contents": "Effect of depolarizing agents on the adenosine-3',5'-monophosphate content of the bovine superior cervical ganglion. The cAMP content of the bovine superior cervical ganglion increases rapidly when the tissue is incubated in media containing high concentrations of potassium and theophylline. This effect of high K+ is mimicked by Rb+, Cs+ and NH4+. The depolarizing substances veratridine and ouabain also cause an increase in the concentration of ganglionic cAMP; the effect of ouabain develops more slowly than that of veratridine. Tetracaine, in high concentrations, reduces the response to potassium, whereas it reduces the response to veratridine at much lower concentrations. Tetrodotoxin, at a concentration that barely affects the response to potassium, prevents the response to veratridine."} {"id": "PMID:172812", "title": "DNA content of mouse hepatoma nuclei determined by Feulgen cytophotometry.", "content": "The DNA content of mouse hepatoma nuclei was determined by means of Feulgen cytophotometry. The tumor nuclei showed a wide range of polyploidy and aneuploidy characteristic of malignant cells.", "contents": "DNA content of mouse hepatoma nuclei determined by Feulgen cytophotometry. The DNA content of mouse hepatoma nuclei was determined by means of Feulgen cytophotometry. The tumor nuclei showed a wide range of polyploidy and aneuploidy characteristic of malignant cells."} {"id": "PMID:172816", "title": "Scotomatous defects in the central visual field in pituitary adenomas.", "content": "In a series of 46 cases of pituitary adenomata (34 solid, 6 with yellow cyst, and 6 with hemorrhagic cyst), we found central scotomatous field defects in 8 patients. Of these 8 scotomatous cases 4 were associated with tumour containing a hemorrhagic cyst. We suggest that rapid expansion of the tumour is one of the principal etiological factors in the production of scotomatous instead of bitemporal field defects in patients with pituitary adenomas.", "contents": "Scotomatous defects in the central visual field in pituitary adenomas. In a series of 46 cases of pituitary adenomata (34 solid, 6 with yellow cyst, and 6 with hemorrhagic cyst), we found central scotomatous field defects in 8 patients. Of these 8 scotomatous cases 4 were associated with tumour containing a hemorrhagic cyst. We suggest that rapid expansion of the tumour is one of the principal etiological factors in the production of scotomatous instead of bitemporal field defects in patients with pituitary adenomas."} {"id": "PMID:172818", "title": "[Studies on cyclic 3', 5'-AMP system in human brain and its clinical application in Neurosurgical practice (author's transl)].", "content": "Literatures showed that cyclic AMP of cultured neoplastic cells of any kind was very low in concentration and also the effect of cyclic AMP and its derivatives on the malignant cells, especially on the malignant glioma, was already reported in vivo or in vitro from several neurosurgical units. The intrinsic content of cyclic AMP of the human cerebrum and the human brain tumors was first reported by authors in 1971. In this presentation the authors intended to confirm that the lower concentration of the cyclic AMP the more histologically malignant cerebral neoplasm, as well as in the cerebrospinal fluid, was observed. Concentration of cyclic AMP in the subcortical white matter, glioma, meningioma and medullobalstoma was much lower than in the gray matter tissue, however, it was not clear that the difference of the cyclic AMP concentration be possibly related to the malignancy of the human brain tumor. Furthermore, the cyclic AMP content of the cerebrospinal fluid of the patients with various brain tumor was not clearly different. The activity of adenyl cyclase was reported the highest in the synaptosome-containing fraction of the rat brain homogenate and this fact was significantly consistent with the finding that the highest concentration of the cyclic AMP was found in the human grey matter tissue. With the human brain gray matter authors determined successfully the activity of the human cerebral phosphodiesterase, which was probably localized in the post-synaptic membrane and was 158 nmole/mg protein/min. Its apparent Km was 0.9 x 10(-4) M. The results reported above have suggested the important participation of the cyclic AMP to cerebral synaptic transmission of nerve impulses, which was studied by light and electron-microscopic autoradiography utilizing the pulse labeling method with 3H-adenine. According to our study the majority of the adenyl cyclase of the human cerebrum was located synaptic structure and the finding obtained was quite compatible, as the first morphological study, with previously reported biochemical analyses. It was indicated that the cyclic AMP in the human brain was concerned to the cerebral synaptic transmission of nerve impulses and this should be very interesting and important to the clinical application for recovering cerebral function of neurosurgical patients.", "contents": "[Studies on cyclic 3', 5'-AMP system in human brain and its clinical application in Neurosurgical practice (author's transl)]. Literatures showed that cyclic AMP of cultured neoplastic cells of any kind was very low in concentration and also the effect of cyclic AMP and its derivatives on the malignant cells, especially on the malignant glioma, was already reported in vivo or in vitro from several neurosurgical units. The intrinsic content of cyclic AMP of the human cerebrum and the human brain tumors was first reported by authors in 1971. In this presentation the authors intended to confirm that the lower concentration of the cyclic AMP the more histologically malignant cerebral neoplasm, as well as in the cerebrospinal fluid, was observed. Concentration of cyclic AMP in the subcortical white matter, glioma, meningioma and medullobalstoma was much lower than in the gray matter tissue, however, it was not clear that the difference of the cyclic AMP concentration be possibly related to the malignancy of the human brain tumor. Furthermore, the cyclic AMP content of the cerebrospinal fluid of the patients with various brain tumor was not clearly different. The activity of adenyl cyclase was reported the highest in the synaptosome-containing fraction of the rat brain homogenate and this fact was significantly consistent with the finding that the highest concentration of the cyclic AMP was found in the human grey matter tissue. With the human brain gray matter authors determined successfully the activity of the human cerebral phosphodiesterase, which was probably localized in the post-synaptic membrane and was 158 nmole/mg protein/min. Its apparent Km was 0.9 x 10(-4) M. The results reported above have suggested the important participation of the cyclic AMP to cerebral synaptic transmission of nerve impulses, which was studied by light and electron-microscopic autoradiography utilizing the pulse labeling method with 3H-adenine. According to our study the majority of the adenyl cyclase of the human cerebrum was located synaptic structure and the finding obtained was quite compatible, as the first morphological study, with previously reported biochemical analyses. It was indicated that the cyclic AMP in the human brain was concerned to the cerebral synaptic transmission of nerve impulses and this should be very interesting and important to the clinical application for recovering cerebral function of neurosurgical patients."} {"id": "PMID:172819", "title": "[Viruses and brain tumors (author's transl)].", "content": "This brief review paper deals mainly with oncogenic DNA viruses originally isolated from human patients, i.e., human adenoviruses and human papova JC viruses. Human adenovirus type 12 was first isolated in 1953 in cell cultures derived from the adenoids of infected children. Since then, 32 antigenic types of human adenovirus have been identified. At least eight serotypes (12, 18, 31, 3, 7, 14, 16, and 21) are now known to be capable of producing tumors in newborn rodents. A direct causal relationship between a human adenovirus and malignant transformations in target cells (sensory neuronal precursors) has been definitely established by the development of a medullo-epitheliomatous neoplasm in the brain and spinal cord of an outbred strain of CD rats at as high an incidence as 90%. Intraocular inoculation of adenovirus in newborn rats within one week also has produced typical retinoblastomatous neoplasms. The remarkably uniform histopathologic appearance of all these malignancies in nervous tissue can be attributed to a primitive neuro-epitheliomatous neoplasm derived from sensory microneuron precursors that densely populate both the ventricular zone and the premature sensory retina at the point of virus inoculation. All of these brain and retinal tumors appear to share a common tumor phenotype, as all tumor cells contain cilia with the same morphology (a 9+0 pattern of doublets associated with a pair of centrioles). The production of adenovirus tumor-specific neoantigen (T), an earmark of the viral genome, can be regularly demonstrated by the immunofluorescein microscopic procedure. All transformed cells within both the ventricular zone and the retinal ganglion cell anlage thus appear to continue the production of (T) antigens. These findings lead us to assume that the target cell determinants in adenovirus tumorigenesis may reside in differentiating microneuron precursors ordained for the sensory neuronal complex.", "contents": "[Viruses and brain tumors (author's transl)]. This brief review paper deals mainly with oncogenic DNA viruses originally isolated from human patients, i.e., human adenoviruses and human papova JC viruses. Human adenovirus type 12 was first isolated in 1953 in cell cultures derived from the adenoids of infected children. Since then, 32 antigenic types of human adenovirus have been identified. At least eight serotypes (12, 18, 31, 3, 7, 14, 16, and 21) are now known to be capable of producing tumors in newborn rodents. A direct causal relationship between a human adenovirus and malignant transformations in target cells (sensory neuronal precursors) has been definitely established by the development of a medullo-epitheliomatous neoplasm in the brain and spinal cord of an outbred strain of CD rats at as high an incidence as 90%. Intraocular inoculation of adenovirus in newborn rats within one week also has produced typical retinoblastomatous neoplasms. The remarkably uniform histopathologic appearance of all these malignancies in nervous tissue can be attributed to a primitive neuro-epitheliomatous neoplasm derived from sensory microneuron precursors that densely populate both the ventricular zone and the premature sensory retina at the point of virus inoculation. All of these brain and retinal tumors appear to share a common tumor phenotype, as all tumor cells contain cilia with the same morphology (a 9+0 pattern of doublets associated with a pair of centrioles). The production of adenovirus tumor-specific neoantigen (T), an earmark of the viral genome, can be regularly demonstrated by the immunofluorescein microscopic procedure. All transformed cells within both the ventricular zone and the retinal ganglion cell anlage thus appear to continue the production of (T) antigens. These findings lead us to assume that the target cell determinants in adenovirus tumorigenesis may reside in differentiating microneuron precursors ordained for the sensory neuronal complex."} {"id": "PMID:172821", "title": "Normal activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate in erythrocytes of patients with primary metabolic gout.", "content": "The activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate (PRPP) was studied in. The erythrocytes of 34 patients with idiopathic metabolic gout. The activities of the oxidative pentose shunt, of the hypoxanthine-guanine and adenine phosphoribosyltransferases (HGPRT, APRT) and of PRPP synthetase, as well as the rates of PRPP generation and of adenine incorporation into nucleotides were found to be normal in the erythrocytes of all these patients. Four patients with metabolic gout due to enzymatic abnormalities, two relatives with partial deficiency of HGPRT and two relatives with mutant feedback-resistant PRPP synthetase, were studied for comparison. The significance of the results is discussed in relation to postulated mechanisms for purine overproduction in metabolic gout.", "contents": "Normal activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate in erythrocytes of patients with primary metabolic gout. The activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate (PRPP) was studied in. The erythrocytes of 34 patients with idiopathic metabolic gout. The activities of the oxidative pentose shunt, of the hypoxanthine-guanine and adenine phosphoribosyltransferases (HGPRT, APRT) and of PRPP synthetase, as well as the rates of PRPP generation and of adenine incorporation into nucleotides were found to be normal in the erythrocytes of all these patients. Four patients with metabolic gout due to enzymatic abnormalities, two relatives with partial deficiency of HGPRT and two relatives with mutant feedback-resistant PRPP synthetase, were studied for comparison. The significance of the results is discussed in relation to postulated mechanisms for purine overproduction in metabolic gout."} {"id": "PMID:172817", "title": "[Peripheral nerve damage in upper extremities in glass cutters].", "content": "A group of glass cutters working with flint-glass was analysed in view of their susceptibility to ulnar nerve crush injury. The group comprised 429 cutters from Eastern Bohemia working in the Bohemia manufacture. The type of work done by cutters is described with particular reference to the way in which they rest their upper extremities during work and to the duration of work. Subjective symptoms were present in 44.7% of workers. The following neurological abnormalities were found during examination: hypaesthesia in 36.8%, motor activity impairment in 21.9%, muscular atrophy in 8.1%. Autonomic abnormalities involved hands in 29.1% of workers. Slight electromyographic abnormalities were demonstrated not only in the innervation area of the ulnar nerve but also in that of the median nerve. The authors discuss their views on the aetiology of the disease and criteria used in medical evaluation of ability to work in these workers.", "contents": "[Peripheral nerve damage in upper extremities in glass cutters]. A group of glass cutters working with flint-glass was analysed in view of their susceptibility to ulnar nerve crush injury. The group comprised 429 cutters from Eastern Bohemia working in the Bohemia manufacture. The type of work done by cutters is described with particular reference to the way in which they rest their upper extremities during work and to the duration of work. Subjective symptoms were present in 44.7% of workers. The following neurological abnormalities were found during examination: hypaesthesia in 36.8%, motor activity impairment in 21.9%, muscular atrophy in 8.1%. Autonomic abnormalities involved hands in 29.1% of workers. Slight electromyographic abnormalities were demonstrated not only in the innervation area of the ulnar nerve but also in that of the median nerve. The authors discuss their views on the aetiology of the disease and criteria used in medical evaluation of ability to work in these workers."} {"id": "PMID:172827", "title": "Fetal lung maturatio. III. Amniotic fluid phosphatidic acid phosphohydrolase (PAPase) and its relation to the lecithin/sphingomyelin ratio.", "content": "The purpose of this study was to establish 1) the sequential changes in specific activity of phosphatidic acid phosphohydrolase (PAPase) in amniotic fluid and its relation to the lecithin/sphingomyelin (L/S) ratio; and 2) the origin of amniotic fluid PAPase. the increase in the amniotic fluid L/S ratio is preceded by an increase in PAPase activity, rising from 15 nmoles of phosphate released per milligram of protein per hour at 30 weeks to 100 nmoles at 37 weeks. The mean PAPase activity in the nasopharyngeal fluid of the infant is 456 nmoles of phosphate released per ml per hour, the amniotic fluid mean PAPase activity at delivery being 129 nmoles (P less than 0.01). These findings are consistent with the view that amniotic fluid PAPase originates, in part, from the fetal lung and likely participates in the regulation of the synthesis of lecithin.", "contents": "Fetal lung maturatio. III. Amniotic fluid phosphatidic acid phosphohydrolase (PAPase) and its relation to the lecithin/sphingomyelin ratio. The purpose of this study was to establish 1) the sequential changes in specific activity of phosphatidic acid phosphohydrolase (PAPase) in amniotic fluid and its relation to the lecithin/sphingomyelin (L/S) ratio; and 2) the origin of amniotic fluid PAPase. the increase in the amniotic fluid L/S ratio is preceded by an increase in PAPase activity, rising from 15 nmoles of phosphate released per milligram of protein per hour at 30 weeks to 100 nmoles at 37 weeks. The mean PAPase activity in the nasopharyngeal fluid of the infant is 456 nmoles of phosphate released per ml per hour, the amniotic fluid mean PAPase activity at delivery being 129 nmoles (P less than 0.01). These findings are consistent with the view that amniotic fluid PAPase originates, in part, from the fetal lung and likely participates in the regulation of the synthesis of lecithin."} {"id": "PMID:172828", "title": "The partial purification of Clostridium perfringens beta toxin.", "content": "An attempt was made to purify Clostridium perfringens Beta toxin. Crude toxin prepared by ammonium sulphate precipitation of culture supernatants was purified by chromatography on Sephadex G50, Sephadex G100 and DEAE cellulose. This material, although highly purified was not homogeneous on polyacrylamide gel electrophoresis. It had a toxicity of 800 000 mouse MLDs/mg N, a typical protein absorption spectrum in the UV region, an iso-electric point of 5, 6 and the main component had a molecular mass of 42 000 +/- 2 000 (estimated by electrophoresis in sodium dodecyl sulphate containing polyacrylamide gels).", "contents": "The partial purification of Clostridium perfringens beta toxin. An attempt was made to purify Clostridium perfringens Beta toxin. Crude toxin prepared by ammonium sulphate precipitation of culture supernatants was purified by chromatography on Sephadex G50, Sephadex G100 and DEAE cellulose. This material, although highly purified was not homogeneous on polyacrylamide gel electrophoresis. It had a toxicity of 800 000 mouse MLDs/mg N, a typical protein absorption spectrum in the UV region, an iso-electric point of 5, 6 and the main component had a molecular mass of 42 000 +/- 2 000 (estimated by electrophoresis in sodium dodecyl sulphate containing polyacrylamide gels)."} {"id": "PMID:172832", "title": "[On a case of purulent pericarditis in a young child caused by mycobacterium rhodochrous].", "content": "M. rhodochrous was cultivated from the blood of a 2 1/2 year-old child with purulent pericarditis and is regarded as the causative agent. The process was successfully treated by chemotherapy and surgical measures. The problems of bacteriological diagnostics are discussed in detail with particular reference to the taxonomical differentiation of these agents and the treatment of their infections.", "contents": "[On a case of purulent pericarditis in a young child caused by mycobacterium rhodochrous]. M. rhodochrous was cultivated from the blood of a 2 1/2 year-old child with purulent pericarditis and is regarded as the causative agent. The process was successfully treated by chemotherapy and surgical measures. The problems of bacteriological diagnostics are discussed in detail with particular reference to the taxonomical differentiation of these agents and the treatment of their infections."} {"id": "PMID:172833", "title": "[Distribution of some enzymes in totally stained preparations of cestodes].", "content": "The distribution of succinic dehydrogenase, (see article), glucose-6-phosphat-dehydrogenase, alkaline and acid phosphatases and glucose-6-phosphatase was studied by means of the incubation of whole cestodes. Succinic dehydrogenase, NAD-diaphorase and glucose-6-phosphatdehydrogenase are connected in general with the fixating apparatus of the scolex and genital organs; phosphatases -- with the integument tissues, excretory system and calcareous corpuscles. The results obtained are in complete agreement with the available data on the distribution of the enzymes studied. The incubation method of whole cestodes can be useful for field works.", "contents": "[Distribution of some enzymes in totally stained preparations of cestodes]. The distribution of succinic dehydrogenase, (see article), glucose-6-phosphat-dehydrogenase, alkaline and acid phosphatases and glucose-6-phosphatase was studied by means of the incubation of whole cestodes. Succinic dehydrogenase, NAD-diaphorase and glucose-6-phosphatdehydrogenase are connected in general with the fixating apparatus of the scolex and genital organs; phosphatases -- with the integument tissues, excretory system and calcareous corpuscles. The results obtained are in complete agreement with the available data on the distribution of the enzymes studied. The incubation method of whole cestodes can be useful for field works."} {"id": "PMID:172834", "title": "[Electron microscopic study of the excretory system of the hungry female tick Hyalomma asiaticum P. Sch. et E. Schl. Report II].", "content": "In H. asiaticum the cells of the Malpighian tubules and these of the rectal cas have the uniform structure: the apical surface is covered with microvilli, the basal plasmatic membrane forms relatively small invaginations. As to ultrastructural characters, there is no distinct division of the Malpighian tubule into departments. The distal ends of the tubules are only somewhat enlarged and form the so-called ampulla the cells of which are noticeably flattened. The microvilli and basal folds of the plasmatic membrane in this area of the tubule are indistinct. The cells of the ampulla and the neighbouring area of the tubule are characterized by the presence of inclusions with mucopolysaccharide secretion confined by the membrane. The microvilli are most developed on cells of the proximal ends of the Malpighian tubules. Well developed microvilli of the rectal sac form a striated border each containing a microtube inside. The basal invaginations are developed here better than in the cells of the Malpighian tubules.", "contents": "[Electron microscopic study of the excretory system of the hungry female tick Hyalomma asiaticum P. Sch. et E. Schl. Report II]. In H. asiaticum the cells of the Malpighian tubules and these of the rectal cas have the uniform structure: the apical surface is covered with microvilli, the basal plasmatic membrane forms relatively small invaginations. As to ultrastructural characters, there is no distinct division of the Malpighian tubule into departments. The distal ends of the tubules are only somewhat enlarged and form the so-called ampulla the cells of which are noticeably flattened. The microvilli and basal folds of the plasmatic membrane in this area of the tubule are indistinct. The cells of the ampulla and the neighbouring area of the tubule are characterized by the presence of inclusions with mucopolysaccharide secretion confined by the membrane. The microvilli are most developed on cells of the proximal ends of the Malpighian tubules. Well developed microvilli of the rectal sac form a striated border each containing a microtube inside. The basal invaginations are developed here better than in the cells of the Malpighian tubules."} {"id": "PMID:172838", "title": "[Short-term biological effects of synthetic salmon calcitonin in Paget's disease. Influence of posology].", "content": "In ten patients with Paget's disease of bone (Group I) intramuscular injection of 50 MRC units of synthetic Salmon calcitonin (SCT) induced a marked decrease of serum calcium (-1,444 mg%), serum phosphorus (-1,06 mg%), urinary total hydroxyproline (-71%), and a marked increase of urinary cyclic AMP (+ 114%). These changes occur at maximum 6 hours after the injection with a return to the initial values after 24 hours. In six other patients with Paget's disease (Group II) the acute biological effects were of the same nature and magnitude after the injection of 100 MRC units of SCT. In this group a significant but temporary increase of the plasma parathyroid hormone level was demonstrated. The magnitude of the hypocalcemia seems proportional to the initial serum alkaline phosphatase and urinary hydroxyproline levels. After one month of treatment, the alkaline phosphatase and urinary hydroxyproline have more marked and more regular decrease in group II who received 100 MRC units of SCT daily than in group I who received 50 MRC units three times a week. The cellular mechanisms of these biological changes are discussed. A posology of two daily injections of 50 MRC units of SCT is suggested when a quick and maximum stoppage of pagetic remodeling is required.", "contents": "[Short-term biological effects of synthetic salmon calcitonin in Paget's disease. Influence of posology]. In ten patients with Paget's disease of bone (Group I) intramuscular injection of 50 MRC units of synthetic Salmon calcitonin (SCT) induced a marked decrease of serum calcium (-1,444 mg%), serum phosphorus (-1,06 mg%), urinary total hydroxyproline (-71%), and a marked increase of urinary cyclic AMP (+ 114%). These changes occur at maximum 6 hours after the injection with a return to the initial values after 24 hours. In six other patients with Paget's disease (Group II) the acute biological effects were of the same nature and magnitude after the injection of 100 MRC units of SCT. In this group a significant but temporary increase of the plasma parathyroid hormone level was demonstrated. The magnitude of the hypocalcemia seems proportional to the initial serum alkaline phosphatase and urinary hydroxyproline levels. After one month of treatment, the alkaline phosphatase and urinary hydroxyproline have more marked and more regular decrease in group II who received 100 MRC units of SCT daily than in group I who received 50 MRC units three times a week. The cellular mechanisms of these biological changes are discussed. A posology of two daily injections of 50 MRC units of SCT is suggested when a quick and maximum stoppage of pagetic remodeling is required."} {"id": "PMID:172839", "title": "[Calcium and magnesium concentrations of the renal cortex in the rat. Comparison of 3 methods of tissular extraction of the principal cations].", "content": "We describe three methods for extraction of main tissular cations : a) dry ashing method; b) wet ashing method with HNO3; c) wet method on fresh tissue with HCIO4. This study allows the determination of tissular concentrations of calcium, magnesium in renal cortex of the Rat. Our findings show : a loss of Na, K cations probably by volatilization with dry ashing method ; inability for K determination when HCIO4 method is used ; tissular concentrations are : 4,7 mEq Ca ; 21,6 mEq Mg per kg of wet tissue (wet ashing method with HNO3) ; recovery percentage for magnesium is above 100 % (as previously shown by other authors) ; the dry ashing method is less suitable for extraction than the two other methods ; both wet methods lead to similar results and to a recovery percentage near 100 %.", "contents": "[Calcium and magnesium concentrations of the renal cortex in the rat. Comparison of 3 methods of tissular extraction of the principal cations]. We describe three methods for extraction of main tissular cations : a) dry ashing method; b) wet ashing method with HNO3; c) wet method on fresh tissue with HCIO4. This study allows the determination of tissular concentrations of calcium, magnesium in renal cortex of the Rat. Our findings show : a loss of Na, K cations probably by volatilization with dry ashing method ; inability for K determination when HCIO4 method is used ; tissular concentrations are : 4,7 mEq Ca ; 21,6 mEq Mg per kg of wet tissue (wet ashing method with HNO3) ; recovery percentage for magnesium is above 100 % (as previously shown by other authors) ; the dry ashing method is less suitable for extraction than the two other methods ; both wet methods lead to similar results and to a recovery percentage near 100 %."} {"id": "PMID:172840", "title": "[Herpes simplex virus antibodies in 18 patients submitted to immunosuppressive agents after renal transplantation].", "content": "The titer of circulating antibodies to herpes simplex virus type 1 was tested in 18 patients for a few months before and after renal transplantation. No clinical illness was observed in the group of patients lacking antibodies. On the contrary, half of those with antibodies developed cutaneous eruption within 2 to 4 weeks following treatment with immunosuppressive drugs. No relationship could be found between the appearance of clinical illness and the rise in antibody titer. This lack of correlation could be explained by the multiple modifications occurring in the immune system of the host submitted to immunosuppressive drugs.", "contents": "[Herpes simplex virus antibodies in 18 patients submitted to immunosuppressive agents after renal transplantation]. The titer of circulating antibodies to herpes simplex virus type 1 was tested in 18 patients for a few months before and after renal transplantation. No clinical illness was observed in the group of patients lacking antibodies. On the contrary, half of those with antibodies developed cutaneous eruption within 2 to 4 weeks following treatment with immunosuppressive drugs. No relationship could be found between the appearance of clinical illness and the rise in antibody titer. This lack of correlation could be explained by the multiple modifications occurring in the immune system of the host submitted to immunosuppressive drugs."} {"id": "PMID:172841", "title": "Application of pulse polarography with anodic stripping voltammetry to biological and toxicological analyses for lead and cadmium.", "content": "The development of polarographic techniques within the last thirty years has made possible exceptional increases in sensitivity ; thus the order of concentration studied has passed from 10-3 g ion/1. to 10-10 g ion/1. Pulse polarography with anodic stripping voltammetry is, therefore, particularly suitable for the determination of a large number of the so-called \" biologically essential \" and \" highly toxic \" metals, more often than not present in extremely low concentrations in biological samples which may be of limited volume (blood, for example). Our principal concern has been to describe and apply a method for the determination of lead and cadmium, sufficiently sensitive, precise, practical and rapid for everyday use by biologists and toxicologists. A fortiori this method is applicable in hydrology to the determination of traces of these metals in water.", "contents": "Application of pulse polarography with anodic stripping voltammetry to biological and toxicological analyses for lead and cadmium. The development of polarographic techniques within the last thirty years has made possible exceptional increases in sensitivity ; thus the order of concentration studied has passed from 10-3 g ion/1. to 10-10 g ion/1. Pulse polarography with anodic stripping voltammetry is, therefore, particularly suitable for the determination of a large number of the so-called \" biologically essential \" and \" highly toxic \" metals, more often than not present in extremely low concentrations in biological samples which may be of limited volume (blood, for example). Our principal concern has been to describe and apply a method for the determination of lead and cadmium, sufficiently sensitive, precise, practical and rapid for everyday use by biologists and toxicologists. A fortiori this method is applicable in hydrology to the determination of traces of these metals in water."} {"id": "PMID:172842", "title": "[Mathematical study of size distribution of alveolar mononuclear cells (CMA) in man].", "content": "The mathematical study using the Wicksell transformation of the size distribution of the mononuclear alveolar cells has shown two different populations among the alveolar macrophages obtained from 4 adult men. These two types of cells could be also found out and described by electron microscopy. The large cells (14 microns in diameter) looked like the \"alveolar macrophage \", with many phagolysosomes. The small cells (7 microns in diameter), less numerous (1/3 of the whole population) resembled monocytes. These data in man are compared to those found in rabbits and the role ot two kinds of cells is discussed.", "contents": "[Mathematical study of size distribution of alveolar mononuclear cells (CMA) in man]. The mathematical study using the Wicksell transformation of the size distribution of the mononuclear alveolar cells has shown two different populations among the alveolar macrophages obtained from 4 adult men. These two types of cells could be also found out and described by electron microscopy. The large cells (14 microns in diameter) looked like the \"alveolar macrophage \", with many phagolysosomes. The small cells (7 microns in diameter), less numerous (1/3 of the whole population) resembled monocytes. These data in man are compared to those found in rabbits and the role ot two kinds of cells is discussed."} {"id": "PMID:172843", "title": "[Epithelioid cell. Ultrastructural data during various pathological conditions].", "content": "A morphological study permitted us to show that the epithelioid cell is an active cell, the characteristic vesicles of which seem to be linked to the presence of a glycoprotein substance which passes through the Golgi apparatus and becomes accumlated in the lysosomes owing to their richness in acid phosphatase. A fraction of this substance may be secreted into the extra-cellular medium, without it being possible to determine its precise nature and whether this function is carried out only by this cell.", "contents": "[Epithelioid cell. Ultrastructural data during various pathological conditions]. A morphological study permitted us to show that the epithelioid cell is an active cell, the characteristic vesicles of which seem to be linked to the presence of a glycoprotein substance which passes through the Golgi apparatus and becomes accumlated in the lysosomes owing to their richness in acid phosphatase. A fraction of this substance may be secreted into the extra-cellular medium, without it being possible to determine its precise nature and whether this function is carried out only by this cell."} {"id": "PMID:172844", "title": "Fibroxanthosarcoma of bone.", "content": "A tumour arising from the body of the eighth thoracic vertebra is believed to be the first recordedexample of a primary fibroxanthosarcoma of bone. Apart from the absence of a demonstrable storiform pattern, the histology conformed to that of fibroxanthosarcoma of the soft tissues. Ultrastructural studies showed that asteroid-like bodies seen in the cytoplasm of some tumour cells consisted of aggregated centrioles surrounded by cytoplasmic vacuoles. The finding of Langerhans cell granules in some tumour cells supported their identification as histiocytes. These granules have not previously been recorded in the fibrous histiocytoma group of tumours.", "contents": "Fibroxanthosarcoma of bone. A tumour arising from the body of the eighth thoracic vertebra is believed to be the first recordedexample of a primary fibroxanthosarcoma of bone. Apart from the absence of a demonstrable storiform pattern, the histology conformed to that of fibroxanthosarcoma of the soft tissues. Ultrastructural studies showed that asteroid-like bodies seen in the cytoplasm of some tumour cells consisted of aggregated centrioles surrounded by cytoplasmic vacuoles. The finding of Langerhans cell granules in some tumour cells supported their identification as histiocytes. These granules have not previously been recorded in the fibrous histiocytoma group of tumours."} {"id": "PMID:172848", "title": "Sphingomyelinases in human tissues. II. Absence of a specific enzyme from liver and brain of Niemann-Pick disease, type C.", "content": "Sphingomyelinase was obtained in excellent yield from liver and brain by homogenization with 0.05 M citrate-phosphate buffer, pH 4.5, containing 0.25% Triton-X-100 (v/v) followed by dialysis of the supernatant fluids against 1% glycine. Total recovery of enzyme was slightly less with tissue from Niemann-Pick disease compared with control tissue. Isoelectric focusing of liver and brain extracts was successfully used to resolve several species of sphingomyelinase. Three (I-III) of the five species were partially characterized. Enzyme I (pI 4.6) had a pH optimum of 4.8-5.0 in acetate buffer and a Km value of 0.026 mM. Both sphingomyelinases I and II were the major enzymes, whereas III, IV, and V were found at lower levels. Of the two major species in normal liver and brain (I and II), species I alone persisted in liver from the two cases of type C, while species III, IV, and V were present. In brain, only species II was decreased but the resolution of the brain enzymes was less satisfactory.", "contents": "Sphingomyelinases in human tissues. II. Absence of a specific enzyme from liver and brain of Niemann-Pick disease, type C. Sphingomyelinase was obtained in excellent yield from liver and brain by homogenization with 0.05 M citrate-phosphate buffer, pH 4.5, containing 0.25% Triton-X-100 (v/v) followed by dialysis of the supernatant fluids against 1% glycine. Total recovery of enzyme was slightly less with tissue from Niemann-Pick disease compared with control tissue. Isoelectric focusing of liver and brain extracts was successfully used to resolve several species of sphingomyelinase. Three (I-III) of the five species were partially characterized. Enzyme I (pI 4.6) had a pH optimum of 4.8-5.0 in acetate buffer and a Km value of 0.026 mM. Both sphingomyelinases I and II were the major enzymes, whereas III, IV, and V were found at lower levels. Of the two major species in normal liver and brain (I and II), species I alone persisted in liver from the two cases of type C, while species III, IV, and V were present. In brain, only species II was decreased but the resolution of the brain enzymes was less satisfactory."} {"id": "PMID:172849", "title": "Sphingomyelinases in human tissues. III. Expression of Niemann-Pick disease in cultured skin fibroblasts.", "content": "Sphingomyelinase was effectively extracted cultured fibroblasts homogenized in 1% glycine. The average specific activity was 24.6 nmol substrate hydrolyzed per hr per mg protein. Cultured cells from two cases of Niemann-Pick disease type A and one case of type B had markedly reduced enzyme activity, whereas, in type E cells, total activity was twice normal. Sphingomyelinase was resolved by isoelectric focusing into three peaks of activity (I-II), where I and II were the major forms. Species I had a pI of 4.6, II a pI of 4.8, and III a pI of 5.0. All three peaks, although markedly reduced, were present in cell extracts from both types A and B. All species of enzyme in B cells were found at higher levels than in A cells. Cultured cells from a case of type E contained sphingomyelinase I at a level several fold higher than normal, species II was absent, whereas III was found at near normal levels.", "contents": "Sphingomyelinases in human tissues. III. Expression of Niemann-Pick disease in cultured skin fibroblasts. Sphingomyelinase was effectively extracted cultured fibroblasts homogenized in 1% glycine. The average specific activity was 24.6 nmol substrate hydrolyzed per hr per mg protein. Cultured cells from two cases of Niemann-Pick disease type A and one case of type B had markedly reduced enzyme activity, whereas, in type E cells, total activity was twice normal. Sphingomyelinase was resolved by isoelectric focusing into three peaks of activity (I-II), where I and II were the major forms. Species I had a pI of 4.6, II a pI of 4.8, and III a pI of 5.0. All three peaks, although markedly reduced, were present in cell extracts from both types A and B. All species of enzyme in B cells were found at higher levels than in A cells. Cultured cells from a case of type E contained sphingomyelinase I at a level several fold higher than normal, species II was absent, whereas III was found at near normal levels."} {"id": "PMID:172850", "title": "Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy.", "content": "A male child presented on the first day of life with metabolic acidosis with elevated blood lactate (15 mM), pyruvate (0.4 mM), and free fatty acid (1.3 mM) levels and a blood pH of 7.16. The severity of the acidosis was diminished by intravenous administration of glucose in large doses and by bicarbonate. On two occasions, when the acidosis was particularly severe, peritoneal dialysis using an acetate buffer was required. Restriction of the dietary intake of saturated fatty acids or treatment with nicotinic acid also appeared to diminish the severity of acidosis. No improvement was achieved by the administration of thiamine or biotin. Tissues taken at postmortem showed normal activity of gluconeogenic enzymes and pyruvate dehydrogenase. The activity of pyruvate dehydrogenase in tissue homogenates preincubated with ATP was reduced by 60-75% both in liver of the patient and of the controls because of the inactivation of the enzyme by pyruvate dehydrogenase kinase. Addition of Ca++ and Mg++ to the inactivated enzyme caused a prompt return of the activity to normal in controls but not in the patient. This defect, which was apparent in muscle and liver but not in brain, we attribute to a markedly reduced activity of pyruvate dehydrogenase phosphatase in the patient.", "contents": "Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy. A male child presented on the first day of life with metabolic acidosis with elevated blood lactate (15 mM), pyruvate (0.4 mM), and free fatty acid (1.3 mM) levels and a blood pH of 7.16. The severity of the acidosis was diminished by intravenous administration of glucose in large doses and by bicarbonate. On two occasions, when the acidosis was particularly severe, peritoneal dialysis using an acetate buffer was required. Restriction of the dietary intake of saturated fatty acids or treatment with nicotinic acid also appeared to diminish the severity of acidosis. No improvement was achieved by the administration of thiamine or biotin. Tissues taken at postmortem showed normal activity of gluconeogenic enzymes and pyruvate dehydrogenase. The activity of pyruvate dehydrogenase in tissue homogenates preincubated with ATP was reduced by 60-75% both in liver of the patient and of the controls because of the inactivation of the enzyme by pyruvate dehydrogenase kinase. Addition of Ca++ and Mg++ to the inactivated enzyme caused a prompt return of the activity to normal in controls but not in the patient. This defect, which was apparent in muscle and liver but not in brain, we attribute to a markedly reduced activity of pyruvate dehydrogenase phosphatase in the patient."} {"id": "PMID:172851", "title": "Demonstration of human leukocyte degranulation induced by sera from homozygotes and heterozygotes for cystic fibrosis.", "content": "The ability of epsilon-amino caproic acid (EACA)-treated normal serum and of cystic fibrosis (CF)-affected and carrier sera to promote the release of lysosomal enzymes from sensitized human polymorphonuclear leukocytes (PMN) was assessed through the measurement of beta-glucuronidase and myeloperoxidase activity after exposure of these cells to the various test sera. This study was initiated to extend the analogies between preciliary dyskinesia factor (pre-CDF), separated from the cell-free media of cultures derived from CF homozygous and heterozygous individuals, and C3a anaphylatoxin. The extent of lysosomal degranulation of human PMN exposed to fresh untreated sera of each of five controls, seven CF homozygotes, and eight heterozygotes, as expressed by the amount of beta-glucuronidase releases, was 7.84% (+/- 0.934) for countrol sera, 14.01% (+/- 1.79) for CF-affected sera, and 10.61% (+/- 1.43) for heterozygous sera. The difference between CF homozygotes and control subjects is significatn (P less than 0.0001), as is the difference between CF-affected and carrier individuals (0.001 less than P less than 0.005) and between control subjects and carriers (0.001 less than P less than 0.005), when beta-glucuronidase. However, the differences between control subjects and CF heterozygous individuals are not significant. Treatment of these sera with 1 M EACA gave values for beta-glucuronidase and myeloperoxidase release which are slightly reduced when compared with those obtained with fresh, untreated samples. EACA apparently reduces the activity of beta-glucuronidase released from PMN. Amicon filtration studies of these serum samples demonstrated that degranulating ability and the presence of cilicary dyskinesia, as assessed by rabbit tracheal bioassay, are not always associated. Therefore, the relationship between pre-CDF and the degranulator activity in native CF-affected and carrier sera is unclear, in part because of the limitations inherent in the test systems employed.", "contents": "Demonstration of human leukocyte degranulation induced by sera from homozygotes and heterozygotes for cystic fibrosis. The ability of epsilon-amino caproic acid (EACA)-treated normal serum and of cystic fibrosis (CF)-affected and carrier sera to promote the release of lysosomal enzymes from sensitized human polymorphonuclear leukocytes (PMN) was assessed through the measurement of beta-glucuronidase and myeloperoxidase activity after exposure of these cells to the various test sera. This study was initiated to extend the analogies between preciliary dyskinesia factor (pre-CDF), separated from the cell-free media of cultures derived from CF homozygous and heterozygous individuals, and C3a anaphylatoxin. The extent of lysosomal degranulation of human PMN exposed to fresh untreated sera of each of five controls, seven CF homozygotes, and eight heterozygotes, as expressed by the amount of beta-glucuronidase releases, was 7.84% (+/- 0.934) for countrol sera, 14.01% (+/- 1.79) for CF-affected sera, and 10.61% (+/- 1.43) for heterozygous sera. The difference between CF homozygotes and control subjects is significatn (P less than 0.0001), as is the difference between CF-affected and carrier individuals (0.001 less than P less than 0.005) and between control subjects and carriers (0.001 less than P less than 0.005), when beta-glucuronidase. However, the differences between control subjects and CF heterozygous individuals are not significant. Treatment of these sera with 1 M EACA gave values for beta-glucuronidase and myeloperoxidase release which are slightly reduced when compared with those obtained with fresh, untreated samples. EACA apparently reduces the activity of beta-glucuronidase released from PMN. Amicon filtration studies of these serum samples demonstrated that degranulating ability and the presence of cilicary dyskinesia, as assessed by rabbit tracheal bioassay, are not always associated. Therefore, the relationship between pre-CDF and the degranulator activity in native CF-affected and carrier sera is unclear, in part because of the limitations inherent in the test systems employed."} {"id": "PMID:172853", "title": "Seroepidemiologic survey of varicella: Value of specific fluorescent antibody test.", "content": "The sensitive varicella-zoster fluorescent antibody to membrane antigen (V-Z FAMA) test was used in a seroepidemiologic survey of two outbreaks of varicella involving 30 children. The attack rate of varicella based on clinical observations alone was 60%. The attack rate based on clinical and serological observations lay between 78% and 82%, after excluding those children who had detectable antibody at the time of exposure. No subclinical varicella infection was observed in this small series of patients. No boost in antibody response was observed in immunes who were exposed to varicella. No patients with detectable V-Z antibody by FAMA at the time of exposure developed clinical varicella. The V-Z FAMA test provided helpful information about the immune status of persons exposed to varicella.", "contents": "Seroepidemiologic survey of varicella: Value of specific fluorescent antibody test. The sensitive varicella-zoster fluorescent antibody to membrane antigen (V-Z FAMA) test was used in a seroepidemiologic survey of two outbreaks of varicella involving 30 children. The attack rate of varicella based on clinical observations alone was 60%. The attack rate based on clinical and serological observations lay between 78% and 82%, after excluding those children who had detectable antibody at the time of exposure. No subclinical varicella infection was observed in this small series of patients. No boost in antibody response was observed in immunes who were exposed to varicella. No patients with detectable V-Z antibody by FAMA at the time of exposure developed clinical varicella. The V-Z FAMA test provided helpful information about the immune status of persons exposed to varicella."} {"id": "PMID:172854", "title": "A comparison of the physical and intellectual development of black children with and without sickle-cell trait.", "content": "Sickle-cell trait, a condition present in 7% to 9% of the United States Black population, is usually considered to be a clinically benign condition. However, there is increasing evidence to indicate the contrary, that is, the clinical pathophysiology is variable, ranging from a benign condition in most cases to a relatively few cases of severe pathological involvement. Physical and intellectual growth measures were taken on 19 children with sickle-cell trait (12 boys and 7 girls) from a large study of Black same-sex twin pairs from Philadelphia, Pennsylvania, and compared to measures taken of a sample of normal Black children from 155 monozygotic and dizygotic same-sex twin pairs. Sickle-cell trait carriers were found to weigh less, have smaller upper arm circumference lesser skinfold thickness, and showed less mature skeletal age, differing significantly from normal children. Sickle-cell carriers tended to score lower on four of five intellectual measures, scoring one fifth to one third of a standard deviation lower than normal children.", "contents": "A comparison of the physical and intellectual development of black children with and without sickle-cell trait. Sickle-cell trait, a condition present in 7% to 9% of the United States Black population, is usually considered to be a clinically benign condition. However, there is increasing evidence to indicate the contrary, that is, the clinical pathophysiology is variable, ranging from a benign condition in most cases to a relatively few cases of severe pathological involvement. Physical and intellectual growth measures were taken on 19 children with sickle-cell trait (12 boys and 7 girls) from a large study of Black same-sex twin pairs from Philadelphia, Pennsylvania, and compared to measures taken of a sample of normal Black children from 155 monozygotic and dizygotic same-sex twin pairs. Sickle-cell trait carriers were found to weigh less, have smaller upper arm circumference lesser skinfold thickness, and showed less mature skeletal age, differing significantly from normal children. Sickle-cell carriers tended to score lower on four of five intellectual measures, scoring one fifth to one third of a standard deviation lower than normal children."} {"id": "PMID:172855", "title": "The RWT method for the prediction of adult stature.", "content": "The Roche- Wainer- Thissen (RWT) method estimates the adult stature of an individual from data recorded at a single childhood examination. The data required are recumbent length, nude weight, midparent stature, and hand-wrist skeletal age. If necessary, a measurement of the child's stature can be transformed to be approximately equivalent to recumbent length with little loss of accuracy. When applied to data from three longitudinal growth studies, the prediction errors with the RWT method were smaller than those with the method of Bayley and Pinneau.", "contents": "The RWT method for the prediction of adult stature. The Roche- Wainer- Thissen (RWT) method estimates the adult stature of an individual from data recorded at a single childhood examination. The data required are recumbent length, nude weight, midparent stature, and hand-wrist skeletal age. If necessary, a measurement of the child's stature can be transformed to be approximately equivalent to recumbent length with little loss of accuracy. When applied to data from three longitudinal growth studies, the prediction errors with the RWT method were smaller than those with the method of Bayley and Pinneau."} {"id": "PMID:172857", "title": "Cyclic AMP and the potassium-induced vasodilation.", "content": "The cAMP concentration of bovine facial arteries (helical strips) increased from 0.84 +/- 0.14 to 1.51 +/- 0.24 nmole/g wet weight, when the strips were relaxed by exposure to a physiological salt solution containing 10 instead of 2.7 mM KCl. A similar result (increase from 1.13 +/- 0.15 to 2.07 +/- 0.29 nmole cAMP/g wet weight) was obtained in strips pretreated with 10(-7) g/ml beta-methyldigoxin. These strips reacted to 10 mM KCl with a constriction. Addition of the phosphodiesterase activator N-methyl-imidazole (3 - 10(-3)M) did not affect the mechanical response to 10 mM KCl. It is concluded that for the potassium-induced vasodilation cAMP does not have a mediating function comparable to that in beta-adrenergic relaxation of vascular smooth muscle.", "contents": "Cyclic AMP and the potassium-induced vasodilation. The cAMP concentration of bovine facial arteries (helical strips) increased from 0.84 +/- 0.14 to 1.51 +/- 0.24 nmole/g wet weight, when the strips were relaxed by exposure to a physiological salt solution containing 10 instead of 2.7 mM KCl. A similar result (increase from 1.13 +/- 0.15 to 2.07 +/- 0.29 nmole cAMP/g wet weight) was obtained in strips pretreated with 10(-7) g/ml beta-methyldigoxin. These strips reacted to 10 mM KCl with a constriction. Addition of the phosphodiesterase activator N-methyl-imidazole (3 - 10(-3)M) did not affect the mechanical response to 10 mM KCl. It is concluded that for the potassium-induced vasodilation cAMP does not have a mediating function comparable to that in beta-adrenergic relaxation of vascular smooth muscle."} {"id": "PMID:172858", "title": "Contribution of long chain fatty acids to the energy supply of the rat kidney cortex.", "content": "Tubular fragments from rat kidney cortex were isolated by collagenase and suspended in an incubation medium containing a combination of several renal substrates. Substrate concentrations were in the physiological range. O2 uptake, total CO2 production, and the 14CO2 production from U-14C-labeled palmitate and oleate were measured. During the first minutes of incubation the CO2 production from palmitate and oleate was 10.5% or 6.3%, respectively, of the total CO3 produced. The RQ was 0.897. A subsequent decrease of the total CO2 production at a constant uptake of oxygen indicated a rising contribution of fatty acids to the fuel of respiration. The renal preference for substrates other than longchain fatty acids is discussed.", "contents": "Contribution of long chain fatty acids to the energy supply of the rat kidney cortex. Tubular fragments from rat kidney cortex were isolated by collagenase and suspended in an incubation medium containing a combination of several renal substrates. Substrate concentrations were in the physiological range. O2 uptake, total CO2 production, and the 14CO2 production from U-14C-labeled palmitate and oleate were measured. During the first minutes of incubation the CO2 production from palmitate and oleate was 10.5% or 6.3%, respectively, of the total CO3 produced. The RQ was 0.897. A subsequent decrease of the total CO2 production at a constant uptake of oxygen indicated a rising contribution of fatty acids to the fuel of respiration. The renal preference for substrates other than longchain fatty acids is discussed."} {"id": "PMID:172859", "title": "Vasopressin dependent adenylate cyclase in single segments of rabbit kidney tubule.", "content": "AVP dependent adenylate cyclase activity was measured in single pieces of 8 different tubular segments isolated from collagenase treated rabbit kidneys. High responses were observed in all the tested portions of the collecting tubule, that is its cortical branched part (BCT), its cortical straight part (CCT) and its outer medullary part (MCT). Dose response curves indicated in CCT: 2 fold threshold stimulation at 10(-11) M AVP, 27 fold stimulation at 10(-6) M AVP, half maximal stimulation at about 10(-9) M AVP. Both the medullary (MAL) and, to a lesser extent, the cortical (CAL) portions of the thick ascending limb were also observed to contain AVP sensitive adenylate cyclase (for MAL: 2 fold threshold stimulation at 10(-9) M AVP, 9 fold stimulation at 10(-7) M AVP, half maximal stimulation at 5 X 10(-9) M AVP). In contrast, nearly no responsiveness to AVP was observed in the proximal convoluted tubule, in the thin descending limb of the loop and in the distal convoluted tubule (DCT). The limited response obtained in DCT (which is a structure generally considered as a target site for AVP) as well as the clearcut effect elicited by AVP in MAL (the functioning of which is not known to be controlled by ADH) were expected observations; their possible physiological implications will be discussed.", "contents": "Vasopressin dependent adenylate cyclase in single segments of rabbit kidney tubule. AVP dependent adenylate cyclase activity was measured in single pieces of 8 different tubular segments isolated from collagenase treated rabbit kidneys. High responses were observed in all the tested portions of the collecting tubule, that is its cortical branched part (BCT), its cortical straight part (CCT) and its outer medullary part (MCT). Dose response curves indicated in CCT: 2 fold threshold stimulation at 10(-11) M AVP, 27 fold stimulation at 10(-6) M AVP, half maximal stimulation at about 10(-9) M AVP. Both the medullary (MAL) and, to a lesser extent, the cortical (CAL) portions of the thick ascending limb were also observed to contain AVP sensitive adenylate cyclase (for MAL: 2 fold threshold stimulation at 10(-9) M AVP, 9 fold stimulation at 10(-7) M AVP, half maximal stimulation at 5 X 10(-9) M AVP). In contrast, nearly no responsiveness to AVP was observed in the proximal convoluted tubule, in the thin descending limb of the loop and in the distal convoluted tubule (DCT). The limited response obtained in DCT (which is a structure generally considered as a target site for AVP) as well as the clearcut effect elicited by AVP in MAL (the functioning of which is not known to be controlled by ADH) were expected observations; their possible physiological implications will be discussed."} {"id": "PMID:172860", "title": "Phase shift in the REM sleep rhythm.", "content": "The periodic alternation between REM and NREM sleep was analyzed. Usually, sleep records of consecutive nights of a subject are regarded to be independent events. However, it may be that consecutive nights are realizations of a continuously ongoing rhythm. This was tested in the present study. The temporal patterns of REM and NREM sleep in sequences of about 30 consecutive nights for 3 subjects were analyzed. The results show that only the onset of the first REM sleep phase during any one night may be predicted from the sleep onset time, whereas a systematic phase shift between consecutive nights was observed in the later REM sleep phases. Thus, the onset of later REM sleep phases is better predicted by assuming a rhythm with stable period length which controls the appearance of REM sleep phases in successive nights. Under the experimental conditions the phase shift was between 5 and 10 min per 24 hrs for the 3 subjects. The result is accordance with Kleitman's basic rest activity cycle (BRAC) hypothesis.", "contents": "Phase shift in the REM sleep rhythm. The periodic alternation between REM and NREM sleep was analyzed. Usually, sleep records of consecutive nights of a subject are regarded to be independent events. However, it may be that consecutive nights are realizations of a continuously ongoing rhythm. This was tested in the present study. The temporal patterns of REM and NREM sleep in sequences of about 30 consecutive nights for 3 subjects were analyzed. The results show that only the onset of the first REM sleep phase during any one night may be predicted from the sleep onset time, whereas a systematic phase shift between consecutive nights was observed in the later REM sleep phases. Thus, the onset of later REM sleep phases is better predicted by assuming a rhythm with stable period length which controls the appearance of REM sleep phases in successive nights. Under the experimental conditions the phase shift was between 5 and 10 min per 24 hrs for the 3 subjects. The result is accordance with Kleitman's basic rest activity cycle (BRAC) hypothesis."} {"id": "PMID:172861", "title": "Neuronal activity in the lateral vestibular necleus of the cat. IV. Postsynaptic potentials evoked by stimulation of peripheral somatic nerves.", "content": "The synaptic input to Deiters neurones evoked by stimulation of peripheral somatic nerves was measured by intracellular recordings. EPSPs with broad receptive fields and latencies which indicate polysynaptic connexions were commonly evoked from the FRA. In other cells, low threshold cutaneous afferents were effective at rather short latencies suggesting oligosynaptic connexions from fast ascending fibres. One example was found of EPSPs due to low threshold muscle afferents. IPSPs due to climging fibre activation of Purkinje cells as observed in most of the neurones were evoked by cutaneous volleys above 1.5-2.0T and muscle volleys above 5T (above 3-3.5T in case of Q). Often, IPSPs were evoked by stimulation of nerves, to the segmental level of which the the vestibulospinal neurone under investigation projected. A small proportion of cells received short latency IPSPs involving direct fast mossy fibre tracts, which were evoked from low threshold cutaneous afferents. IPSPs due to polysynaptic mossy fibre activation of Purkinje cells were evoked from the FRA bilaterally and from ipsilateral cutaneous afferents at 1.5-2.0T (\"prolonged inhibition\"). Prolonged excitatory/inhibitory events mediated by mossy fibre pathways may be involved in quadruped locomotion or other processes making use of a broad motor integration.", "contents": "Neuronal activity in the lateral vestibular necleus of the cat. IV. Postsynaptic potentials evoked by stimulation of peripheral somatic nerves. The synaptic input to Deiters neurones evoked by stimulation of peripheral somatic nerves was measured by intracellular recordings. EPSPs with broad receptive fields and latencies which indicate polysynaptic connexions were commonly evoked from the FRA. In other cells, low threshold cutaneous afferents were effective at rather short latencies suggesting oligosynaptic connexions from fast ascending fibres. One example was found of EPSPs due to low threshold muscle afferents. IPSPs due to climging fibre activation of Purkinje cells as observed in most of the neurones were evoked by cutaneous volleys above 1.5-2.0T and muscle volleys above 5T (above 3-3.5T in case of Q). Often, IPSPs were evoked by stimulation of nerves, to the segmental level of which the the vestibulospinal neurone under investigation projected. A small proportion of cells received short latency IPSPs involving direct fast mossy fibre tracts, which were evoked from low threshold cutaneous afferents. IPSPs due to polysynaptic mossy fibre activation of Purkinje cells were evoked from the FRA bilaterally and from ipsilateral cutaneous afferents at 1.5-2.0T (\"prolonged inhibition\"). Prolonged excitatory/inhibitory events mediated by mossy fibre pathways may be involved in quadruped locomotion or other processes making use of a broad motor integration."} {"id": "PMID:172862", "title": "Changes in chemosensitivity of developing chick muscle fibres in relation to endplate formation.", "content": "1. The sensitivity to acetylcholine (ACh) of the fast posterior latissimus dorsi (PLD) and slow anterior latissimus dorsi (ALD) during embryonic development was studied and compared. The sensitivities were expressed as a ratio of the maximal tetanic tension and tension developed in response to ACh. 2. Up to the 17th day of incubation both muscles are sensitive to ACh to a similar extent; at the 18th day the sensitivity of the PLD muscle decreases and continues to do so until hatching and thereafter. 3. Since the decrease in sensitivity of PLD muscles takes place a few days after innervation, it is suggested that this is caused by activity of the motor nerve. To test this curare (dTc) and hemicholinium (HC-3), drugs that interfere with neuromuscular transmission, were injected into the yolk sac of the embryos when nervemuscle connections are usually established. In the curare and HC-3 treated embryos the desensitization of the PLD muscles did not take place. 4. The distribution of endplates on PLD muscles from drug treated 20-21 day old embryos was compared to that of untreated controls. Whereas control PLD muscles have only one band of endplates, muscles from curarized embryos and HC-3 treated embryos have several bands of endplates, and many muscle fibres with multiple innervation were found. 5. It is suggested that nerve fibres which make connections with PLD muscle fibres bring about a decline in chemosensitivity by releasing more transmitter, and thereby prevent further nerve muscle connections from being made along the same muscle fibre.", "contents": "Changes in chemosensitivity of developing chick muscle fibres in relation to endplate formation. 1. The sensitivity to acetylcholine (ACh) of the fast posterior latissimus dorsi (PLD) and slow anterior latissimus dorsi (ALD) during embryonic development was studied and compared. The sensitivities were expressed as a ratio of the maximal tetanic tension and tension developed in response to ACh. 2. Up to the 17th day of incubation both muscles are sensitive to ACh to a similar extent; at the 18th day the sensitivity of the PLD muscle decreases and continues to do so until hatching and thereafter. 3. Since the decrease in sensitivity of PLD muscles takes place a few days after innervation, it is suggested that this is caused by activity of the motor nerve. To test this curare (dTc) and hemicholinium (HC-3), drugs that interfere with neuromuscular transmission, were injected into the yolk sac of the embryos when nervemuscle connections are usually established. In the curare and HC-3 treated embryos the desensitization of the PLD muscles did not take place. 4. The distribution of endplates on PLD muscles from drug treated 20-21 day old embryos was compared to that of untreated controls. Whereas control PLD muscles have only one band of endplates, muscles from curarized embryos and HC-3 treated embryos have several bands of endplates, and many muscle fibres with multiple innervation were found. 5. It is suggested that nerve fibres which make connections with PLD muscle fibres bring about a decline in chemosensitivity by releasing more transmitter, and thereby prevent further nerve muscle connections from being made along the same muscle fibre."} {"id": "PMID:172863", "title": "[Scintigraphy of the choroid plexus (choroid plexography)].", "content": "An increase concentration of pertechnate in the choroid plexus was demonstrated in 21 patients pretreated with tin pyrophosphate injected intravenously 24 hours before the examination. Using this technique, the choroid plexus are seen quite clearly, giving indirectly a picture of the intracerebral ventricles. A dynamic study was carried out in 12 patients, 3 of whom had abnormalities of the cerebrospinal fluid circulation demonstrated by isotope cisternography. The results obtained were characterised by a typical diphasic curve with variations in the pathological cases.", "contents": "[Scintigraphy of the choroid plexus (choroid plexography)]. An increase concentration of pertechnate in the choroid plexus was demonstrated in 21 patients pretreated with tin pyrophosphate injected intravenously 24 hours before the examination. Using this technique, the choroid plexus are seen quite clearly, giving indirectly a picture of the intracerebral ventricles. A dynamic study was carried out in 12 patients, 3 of whom had abnormalities of the cerebrospinal fluid circulation demonstrated by isotope cisternography. The results obtained were characterised by a typical diphasic curve with variations in the pathological cases."} {"id": "PMID:172867", "title": "[Ultrastructural abnormalities of the chondrocytes in pycnodysostosis. Their relation to a disorder of lipid metabolism].", "content": "The ultrastructural study of the growth cartilage of pycnodysostosis reveals the presence of abnormal inclusions in the majority of the chondrocytes. The inclusions are single membrane bound and contain granular material and lamellar irregularly interwoven structures which at very high magnification appear to be made up of dense parallel bands. These vacuoles displace adjacent structures and some of them appear to be closely related to the Golgi apparatus. In addition, appearances are sometimes seen which suggest the expulsion of the vacuoles into the cell capsules. The abnormal chondrocyte inclusions are visible by optic microscopy and stained with Nile blue on frozen section. Thus, histochemical and ultrastructural characteristics suggest a lipid (probably phospholipid) content. Many authors have already stressed the role of lipids in the process of calcification. The abnormalities described might bear some relation to the densification of the skeleton seen in pycnodysostosis.", "contents": "[Ultrastructural abnormalities of the chondrocytes in pycnodysostosis. Their relation to a disorder of lipid metabolism]. The ultrastructural study of the growth cartilage of pycnodysostosis reveals the presence of abnormal inclusions in the majority of the chondrocytes. The inclusions are single membrane bound and contain granular material and lamellar irregularly interwoven structures which at very high magnification appear to be made up of dense parallel bands. These vacuoles displace adjacent structures and some of them appear to be closely related to the Golgi apparatus. In addition, appearances are sometimes seen which suggest the expulsion of the vacuoles into the cell capsules. The abnormal chondrocyte inclusions are visible by optic microscopy and stained with Nile blue on frozen section. Thus, histochemical and ultrastructural characteristics suggest a lipid (probably phospholipid) content. Many authors have already stressed the role of lipids in the process of calcification. The abnormalities described might bear some relation to the densification of the skeleton seen in pycnodysostosis."} {"id": "PMID:172877", "title": "Prazosin: biochemistry and structure-activity studies.", "content": "Prazosin, a structurally and mechanistically novel antihypertensive agent, is the culmination of a systematic synthesis and pharmacologic developmental effort which had as its goal the development of an agent that would lower blood pressure by direct vasodilation. Pharmacologic studies have demonstrated that the vasodilator action of prazosin is confined primarily to the arterioles and that antihypertensive effects are unaccompanied by excessive increases in heart rate. Evidence is presented rationalizing these observations on a biochemical basis. Results of inhibitory studies with isolated cyclic nucleotide phosphodiesterases are consistent with the hypothesis that prazosin elicits its therapeutic effects by increasing intracellular levels of cyclic AMP at vascular sites and intracellular levels of cyclic GMP at cholinergic receptor sites in the heart. Tissue distribution studies with radioactive prazosin-2-14C are in accord with this rationale and further support the mechanistic conclusions reached on the basis of pharmacologic observations. Pharmacokinetic and biotransformation studies indicate that prazosin is well absorbed and is excreted principally in metabolized form with biliary excretion being the major route of elimination. A high margin of safety for prazosin has been established in safety evaluation studies in a variety of animal species.", "contents": "Prazosin: biochemistry and structure-activity studies. Prazosin, a structurally and mechanistically novel antihypertensive agent, is the culmination of a systematic synthesis and pharmacologic developmental effort which had as its goal the development of an agent that would lower blood pressure by direct vasodilation. Pharmacologic studies have demonstrated that the vasodilator action of prazosin is confined primarily to the arterioles and that antihypertensive effects are unaccompanied by excessive increases in heart rate. Evidence is presented rationalizing these observations on a biochemical basis. Results of inhibitory studies with isolated cyclic nucleotide phosphodiesterases are consistent with the hypothesis that prazosin elicits its therapeutic effects by increasing intracellular levels of cyclic AMP at vascular sites and intracellular levels of cyclic GMP at cholinergic receptor sites in the heart. Tissue distribution studies with radioactive prazosin-2-14C are in accord with this rationale and further support the mechanistic conclusions reached on the basis of pharmacologic observations. Pharmacokinetic and biotransformation studies indicate that prazosin is well absorbed and is excreted principally in metabolized form with biliary excretion being the major route of elimination. A high margin of safety for prazosin has been established in safety evaluation studies in a variety of animal species."} {"id": "PMID:172883", "title": "Renal transplantation in the very young child.", "content": "Thirteen children, aged between one and five years, received transplants and 11, all related-donor recipients, are alive (mean follow-up 2.2 yr). Five had congenital nephrotic syndrome, 5 had hypoplastic-dysplastic kidneys and one each had polycystic kidneys, nephroblastoma and glomerulonephritis. One child died of peritonitis and one died following irrevocable rejection. Two children required retransplantation. The present serum creatinine of the survivors is 0.67 +/- 0.23 (x +/- SD)mg/100ml. Eight of the 11 survivors have shown catch-up growth. Thus we conclude that related-donor transplantation is warranted in children having reached the age of one year and six kilograms in body weight.", "contents": "Renal transplantation in the very young child. Thirteen children, aged between one and five years, received transplants and 11, all related-donor recipients, are alive (mean follow-up 2.2 yr). Five had congenital nephrotic syndrome, 5 had hypoplastic-dysplastic kidneys and one each had polycystic kidneys, nephroblastoma and glomerulonephritis. One child died of peritonitis and one died following irrevocable rejection. Two children required retransplantation. The present serum creatinine of the survivors is 0.67 +/- 0.23 (x +/- SD)mg/100ml. Eight of the 11 survivors have shown catch-up growth. Thus we conclude that related-donor transplantation is warranted in children having reached the age of one year and six kilograms in body weight."} {"id": "PMID:172884", "title": "Circadian rhythm of plasma renin activity and plasma aldosterone in normal man and in renal allograft recipients.", "content": "In normal supine man, a marked circadian rhythm was found in plasma renin activity (PRA) and in plasma aldosterone concentration, with highest levels in the morning and lowest in the evening. Short-term suppression of ACTH by dexamethasone did not eliminate the circadian variation of plasma aldosterone. In patients with a transplanted and thus denervated kidney, no such rhythm of PRA could be observed. From our data it is suggested that the normal circadian rhythm of PRA depends on intact renal innervation and is controlled by the central nervous system.", "contents": "Circadian rhythm of plasma renin activity and plasma aldosterone in normal man and in renal allograft recipients. In normal supine man, a marked circadian rhythm was found in plasma renin activity (PRA) and in plasma aldosterone concentration, with highest levels in the morning and lowest in the evening. Short-term suppression of ACTH by dexamethasone did not eliminate the circadian variation of plasma aldosterone. In patients with a transplanted and thus denervated kidney, no such rhythm of PRA could be observed. From our data it is suggested that the normal circadian rhythm of PRA depends on intact renal innervation and is controlled by the central nervous system."} {"id": "PMID:172885", "title": "Pulmonary infections after kidney transplantation.", "content": "Seventy-five pulmonary infections out of 173 kidney transplantations have been observed in 62 graft-recipients, from 1965 to 1973. The aetiologic organism is a bacteria in 80% of the cases, a fungus in 8% of the cases, cytomegalovirus and Pneumocystis Carinii in 11% of the cases. A close relationship between infection and a previous transplant crisis was noted in 66% of the cases. The most efficient diagnostic procedures were pleural and open lung biopsy as well as cultures of blood, pleural fluid and tracheobronchial secretions. Treatment was effective in 60% of bacterial and Pneumocystitis Carinii infections; on the other hand, it was less useful in fungal infections and totally ineffective in cytomegalovirus infections. Despite a possible increase in the risk of rejection, reduction or even arrest of immunosuppressive therapy is recommended in severe infections.", "contents": "Pulmonary infections after kidney transplantation. Seventy-five pulmonary infections out of 173 kidney transplantations have been observed in 62 graft-recipients, from 1965 to 1973. The aetiologic organism is a bacteria in 80% of the cases, a fungus in 8% of the cases, cytomegalovirus and Pneumocystis Carinii in 11% of the cases. A close relationship between infection and a previous transplant crisis was noted in 66% of the cases. The most efficient diagnostic procedures were pleural and open lung biopsy as well as cultures of blood, pleural fluid and tracheobronchial secretions. Treatment was effective in 60% of bacterial and Pneumocystitis Carinii infections; on the other hand, it was less useful in fungal infections and totally ineffective in cytomegalovirus infections. Despite a possible increase in the risk of rejection, reduction or even arrest of immunosuppressive therapy is recommended in severe infections."} {"id": "PMID:172886", "title": "Control of oscillating glycolysis of yeast by stochastic, periodic, and steady source of substrate: a model and experimental study.", "content": "Type and range of entrainment of glycolytic oscillations by a periodic source of substrate are determined experimentally in yeast extracts. Subharmonic entrainment proves the nonlinear nature of the glycolytic oscillator Random variation of the substrate input yields sustained oscillations of irregular waveform and stable period. The results agree with the predictions of an allosteric model for phosphofructokinase (EC 2.7.1.11; ATP:D-fructose-6-phosphate 1-phosphotransferase), which is the enzyme responsible for periodic operation of glycolysis. A comparison between model and experiment in the case of a constant source of substrate further indicates that the oscillatory dynamics of the glycolytic system can satisfactorily be described by the phosphofructokinase model.", "contents": "Control of oscillating glycolysis of yeast by stochastic, periodic, and steady source of substrate: a model and experimental study. Type and range of entrainment of glycolytic oscillations by a periodic source of substrate are determined experimentally in yeast extracts. Subharmonic entrainment proves the nonlinear nature of the glycolytic oscillator Random variation of the substrate input yields sustained oscillations of irregular waveform and stable period. The results agree with the predictions of an allosteric model for phosphofructokinase (EC 2.7.1.11; ATP:D-fructose-6-phosphate 1-phosphotransferase), which is the enzyme responsible for periodic operation of glycolysis. A comparison between model and experiment in the case of a constant source of substrate further indicates that the oscillatory dynamics of the glycolytic system can satisfactorily be described by the phosphofructokinase model."} {"id": "PMID:172887", "title": "Partial purification of a glucocorticoid receptor.", "content": "A simple method for purification of the glucocorticoid receptor from hepatoma tissue culture cells has been developed. The procedure, which requires only about 24 hr, involves biospecific adsorption of the receptor to deoxycorticosterone derivatized agarose, elution with a glucocorticoid, and gel filtration. The receptor-steroid complex is obtained in 35-40% yield and is about 2000-fold purified. It possesses properties similar to those reported in crude extracts, including sedimentation coefficient in glycerol gradients and activation-dependent binding to nuclei.", "contents": "Partial purification of a glucocorticoid receptor. A simple method for purification of the glucocorticoid receptor from hepatoma tissue culture cells has been developed. The procedure, which requires only about 24 hr, involves biospecific adsorption of the receptor to deoxycorticosterone derivatized agarose, elution with a glucocorticoid, and gel filtration. The receptor-steroid complex is obtained in 35-40% yield and is about 2000-fold purified. It possesses properties similar to those reported in crude extracts, including sedimentation coefficient in glycerol gradients and activation-dependent binding to nuclei."} {"id": "PMID:172888", "title": "Oxygen and cyclic nucleotides in human umbilical artery.", "content": "In the human umbilical artery O2 has a direct contractile effect and is also required for induction of contraction by several other agents. Agonist that cause contraction (bradykinin, histamine, and serotonin) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering adenosine 3':5'-monophosphate (cAMP). They appear to act through two different mechanisms: one Ca++-dependent, the other Ca++-inhibited. O2 increased the cGMP content of the artery in a Ca++-dependent manner without affecting the cAMP content. Inhibitors of oxidative phosphorylation (oligomycin and 2,4-dinitrophenol) did not diminish this effect of O2. O2 was required for demonstration of the Ca++-dependent accumulation of cGMP in response to bradykinin, histamine, and ionophore A23187. The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine on basal cGMP content and on the bradykinin-induced accumulation was also dependent on the presence of O2. Methylene blue and sodium ascorbate caused cGMP accumulation in O2-deprived arteries. Their effects were not diminished in Ca++-depleted arteries and, in fact, seemed to be inhibited when 2.7 mM Ca++ was present in the medium. The effects of these agents and of serotonin on cGMP, which were inhibited by Ca++, were also inhibited by O2. These non Ca++-, non O2-dependent agents (methylene blue, ascorbate, and serotonin) did not, however, permit demonstration of the effects of the Ca++- and O2-dependent agonists on O2-deprived arteries. It appears that there are in the umbilical artery (and probably in other tissues also) at least two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca++- and O2-linked processes.", "contents": "Oxygen and cyclic nucleotides in human umbilical artery. In the human umbilical artery O2 has a direct contractile effect and is also required for induction of contraction by several other agents. Agonist that cause contraction (bradykinin, histamine, and serotonin) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering adenosine 3':5'-monophosphate (cAMP). They appear to act through two different mechanisms: one Ca++-dependent, the other Ca++-inhibited. O2 increased the cGMP content of the artery in a Ca++-dependent manner without affecting the cAMP content. Inhibitors of oxidative phosphorylation (oligomycin and 2,4-dinitrophenol) did not diminish this effect of O2. O2 was required for demonstration of the Ca++-dependent accumulation of cGMP in response to bradykinin, histamine, and ionophore A23187. The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine on basal cGMP content and on the bradykinin-induced accumulation was also dependent on the presence of O2. Methylene blue and sodium ascorbate caused cGMP accumulation in O2-deprived arteries. Their effects were not diminished in Ca++-depleted arteries and, in fact, seemed to be inhibited when 2.7 mM Ca++ was present in the medium. The effects of these agents and of serotonin on cGMP, which were inhibited by Ca++, were also inhibited by O2. These non Ca++-, non O2-dependent agents (methylene blue, ascorbate, and serotonin) did not, however, permit demonstration of the effects of the Ca++- and O2-dependent agonists on O2-deprived arteries. It appears that there are in the umbilical artery (and probably in other tissues also) at least two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca++- and O2-linked processes."} {"id": "PMID:172889", "title": "Dynamic and static quenching of 1,N6-ethenoadenine fluorescence in nicotinamide 1,N6-ethenoadenine dinucleotide and in 1,N6-etheno-9-(3-(indol-3-yl) propyl) adenine.", "content": "For nicotinamide 1,N6-ethenoadenine dinucleotide (epsilonNAD+), the fluorescent analog of NAD+, in neutral aqueous solution the quantum yield has been determined to be 0.028 and the fluorescent lifetime, 2.1 nsec. Simultaneous determination of quantum yields and lifetimes of epsilonNAD+ and of the \"half molecule\" epsilonAMP allows the calculation of the percentage of stacked and open conformations of the dinucleotide. At 25 degrees in neutral aqueous solution there is 45 +/- 5% of stacked forms. The value of the fluorescent impurities, especially those containing the epsilon-adenosine moiety, and a purification procedure using high performance liquid chromatography was devised to obtain fluorescently homogeneous preparations. In order to study the effect on epsilon-adenosine fluorescence caused by the possible close proximity of a tryptophan in a polypeptide chain or protein, we have prepared 1,N6-etheno-9-[3-(indol-3-yl)propyl]adenine (epsilonAde9-C3-Ind3), a model compound in which indole is used as a neutral substitute for tryptophan. Fluorescence studies on epsilonAde9-C3-Ind3 show that the formation of an intramolecular complex results in complete quenching of the epsilon-adenine fluorescence. It is therefore predictable that positioning of the epsilon-adenosine of any fluorescent coenzyme moiety (e.q., epsilonATP, epsilonADP) in close proximity to a tryptophan in a protein will result in complete fluorescence quenching of the former.", "contents": "Dynamic and static quenching of 1,N6-ethenoadenine fluorescence in nicotinamide 1,N6-ethenoadenine dinucleotide and in 1,N6-etheno-9-(3-(indol-3-yl) propyl) adenine. For nicotinamide 1,N6-ethenoadenine dinucleotide (epsilonNAD+), the fluorescent analog of NAD+, in neutral aqueous solution the quantum yield has been determined to be 0.028 and the fluorescent lifetime, 2.1 nsec. Simultaneous determination of quantum yields and lifetimes of epsilonNAD+ and of the \"half molecule\" epsilonAMP allows the calculation of the percentage of stacked and open conformations of the dinucleotide. At 25 degrees in neutral aqueous solution there is 45 +/- 5% of stacked forms. The value of the fluorescent impurities, especially those containing the epsilon-adenosine moiety, and a purification procedure using high performance liquid chromatography was devised to obtain fluorescently homogeneous preparations. In order to study the effect on epsilon-adenosine fluorescence caused by the possible close proximity of a tryptophan in a polypeptide chain or protein, we have prepared 1,N6-etheno-9-[3-(indol-3-yl)propyl]adenine (epsilonAde9-C3-Ind3), a model compound in which indole is used as a neutral substitute for tryptophan. Fluorescence studies on epsilonAde9-C3-Ind3 show that the formation of an intramolecular complex results in complete quenching of the epsilon-adenine fluorescence. It is therefore predictable that positioning of the epsilon-adenosine of any fluorescent coenzyme moiety (e.q., epsilonATP, epsilonADP) in close proximity to a tryptophan in a protein will result in complete fluorescence quenching of the former."} {"id": "PMID:172890", "title": "Biosynthesis of mouse interferon by translation of its messenger RNA in a cell-free system.", "content": "A fraction of mouse RNA containing messenger RNA coding for mouse interferon was translated with high efficiency in a wheat germ system into a fully active product. This product fulfills the criteria for mouse interferon, namely: (1) it was active against vesicular stomatitis virus and herpes simplex virus in mouse cells; (2) its antiviral activity was species specific; (3) its activity was completely neutralized by mouse anti-interferon serum. The synthesis of interferon in this cell-free system requires the presence of spermine.", "contents": "Biosynthesis of mouse interferon by translation of its messenger RNA in a cell-free system. A fraction of mouse RNA containing messenger RNA coding for mouse interferon was translated with high efficiency in a wheat germ system into a fully active product. This product fulfills the criteria for mouse interferon, namely: (1) it was active against vesicular stomatitis virus and herpes simplex virus in mouse cells; (2) its antiviral activity was species specific; (3) its activity was completely neutralized by mouse anti-interferon serum. The synthesis of interferon in this cell-free system requires the presence of spermine."} {"id": "PMID:172891", "title": "Specific endocrine and hormonal receptor changes associated with liver regeneration in adult rats.", "content": "Partial removal of the adult rat liver--a procedure that stimulates liver regeneration--causes arterial levels of insulin and thyroxin to fall and glucagon levels to rise. These changes are correlated with the quantity of liver tissue excised and not solely with nonspecific operative manipulations or with blood glucose levels. During regeneration (about 24 hr postoperatively), hepatic plasma membranes become partially resistant to binding glucagon; this change is specific because it is not detected in laparotomized controls and insulin binding is not significantly altered. It remains to be proven whether any one or more of these specific endocrine changes are casually related to the initiation of hepatic proliferation.", "contents": "Specific endocrine and hormonal receptor changes associated with liver regeneration in adult rats. Partial removal of the adult rat liver--a procedure that stimulates liver regeneration--causes arterial levels of insulin and thyroxin to fall and glucagon levels to rise. These changes are correlated with the quantity of liver tissue excised and not solely with nonspecific operative manipulations or with blood glucose levels. During regeneration (about 24 hr postoperatively), hepatic plasma membranes become partially resistant to binding glucagon; this change is specific because it is not detected in laparotomized controls and insulin binding is not significantly altered. It remains to be proven whether any one or more of these specific endocrine changes are casually related to the initiation of hepatic proliferation."} {"id": "PMID:172892", "title": "Effect of oncogenic virus on muscle differentiation.", "content": "Chick muscle cultures infected with wild-type Rous sarcoma virus form myotubes, but these myotubes vacuolate and by day 6 most have degenerated, leaving only large numbers of transformed mononucleated, replicating cells. Muscle cultures infected with a temperature-sensitive mutant (TS) at permissive temperatures behave as cells infected with wild-type Rous sarcoma virus. TS-infected cells reared for 8 days at nonpermissive temperature form contracting myotubes, plus large numbers of fibroblastic cells. If these cultures are lowered to permissive temperature, within 72 hr the myotubes vacuolate and degenerate, whereas the mononucleated cells transform. If replicating TS-transformed cells after 8 days at permissive temperature are shifted to nonpermissive temperature, within 72 hr many cells fuse and form contracting, post-mitotic myotubes. Creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) levels parallel the formation and degeneration of myotubes during these temperature shifts. If the viral transforming gene is expressed in the post-mitotic myotubes it is lethal, whereas it is not lethal if expressed in replicating percursor myogenic cells. The viral gene expression at permissive temperature blocks further myogenesis depending on the position of the cells in the myogenic program. The virus does not cancel the replicating, transformed myogenic cells' commitment to, or position in, the myogenic lineage. When the transforming action of the virus is suppressed, the normal myogenic program resumes.", "contents": "Effect of oncogenic virus on muscle differentiation. Chick muscle cultures infected with wild-type Rous sarcoma virus form myotubes, but these myotubes vacuolate and by day 6 most have degenerated, leaving only large numbers of transformed mononucleated, replicating cells. Muscle cultures infected with a temperature-sensitive mutant (TS) at permissive temperatures behave as cells infected with wild-type Rous sarcoma virus. TS-infected cells reared for 8 days at nonpermissive temperature form contracting myotubes, plus large numbers of fibroblastic cells. If these cultures are lowered to permissive temperature, within 72 hr the myotubes vacuolate and degenerate, whereas the mononucleated cells transform. If replicating TS-transformed cells after 8 days at permissive temperature are shifted to nonpermissive temperature, within 72 hr many cells fuse and form contracting, post-mitotic myotubes. Creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) levels parallel the formation and degeneration of myotubes during these temperature shifts. If the viral transforming gene is expressed in the post-mitotic myotubes it is lethal, whereas it is not lethal if expressed in replicating percursor myogenic cells. The viral gene expression at permissive temperature blocks further myogenesis depending on the position of the cells in the myogenic program. The virus does not cancel the replicating, transformed myogenic cells' commitment to, or position in, the myogenic lineage. When the transforming action of the virus is suppressed, the normal myogenic program resumes."} {"id": "PMID:172893", "title": "Restoration of ultraviolet-induced unscheduled DNA synthesis of xeroderma pigmentosum cells by the concomitant treatment with bacteriophage T4 endonuclease V and HVJ (Sendai virus).", "content": "Ultraviolet (UV)-induced unscheduled DNA synthesis of xeroderma pigmentosum cells, belonging to complementation groups A, B, C, D, and E, was restored to the normal level by concomitant treatment of the cells with T4 endonuclease V and UV-inactivated HVJ (Sendai virus). The present results suggest that (1) T4 endonuclease molecules were inserted effectively into the cells by the interaction of HVJ with the cell membranes, (2) the enzyme was functional on human chromosomal DNA which had been damaged by UV irradiation in the viable cells, (3) all the studied groups of xeroderma pigmentosum (\"variant\" was not tested) were defective in the first step (incision) of excision repair.", "contents": "Restoration of ultraviolet-induced unscheduled DNA synthesis of xeroderma pigmentosum cells by the concomitant treatment with bacteriophage T4 endonuclease V and HVJ (Sendai virus). Ultraviolet (UV)-induced unscheduled DNA synthesis of xeroderma pigmentosum cells, belonging to complementation groups A, B, C, D, and E, was restored to the normal level by concomitant treatment of the cells with T4 endonuclease V and UV-inactivated HVJ (Sendai virus). The present results suggest that (1) T4 endonuclease molecules were inserted effectively into the cells by the interaction of HVJ with the cell membranes, (2) the enzyme was functional on human chromosomal DNA which had been damaged by UV irradiation in the viable cells, (3) all the studied groups of xeroderma pigmentosum (\"variant\" was not tested) were defective in the first step (incision) of excision repair."} {"id": "PMID:172894", "title": "Possible peptide chain termination mutants in thymide kinase gene of a mammalian virus, herpes simplex virus.", "content": "Mutations in the viral gene coding for the thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) induced by herpes simplex virus have been obtained by selection of virus resistant to bromodeoxyuridine when grown in thymidine-kinase-deficient LMTK- mouse cells. Proteins labeled after infection of Vero (monkey) cells with herpes simplex virus were analyzed by gel electrophoresis and one protein of about 40,000 daltons was consistently altered in a number of thymidine-kinase-deficient mutants. Many viral mutants lacked this peptide and one class of these mutants induced the synthesis of new shorter peptides. Revertant virus could be selected which simultaneously regained the ability to induce thymidine kinase activity, regained the intact thymidine kinase peptide, and lost the ability to synthesize the shorter peptide fragment. These mutants comprise a class of animal virus mutants which have the properties expected of peptide chain termination mutants.", "contents": "Possible peptide chain termination mutants in thymide kinase gene of a mammalian virus, herpes simplex virus. Mutations in the viral gene coding for the thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) induced by herpes simplex virus have been obtained by selection of virus resistant to bromodeoxyuridine when grown in thymidine-kinase-deficient LMTK- mouse cells. Proteins labeled after infection of Vero (monkey) cells with herpes simplex virus were analyzed by gel electrophoresis and one protein of about 40,000 daltons was consistently altered in a number of thymidine-kinase-deficient mutants. Many viral mutants lacked this peptide and one class of these mutants induced the synthesis of new shorter peptides. Revertant virus could be selected which simultaneously regained the ability to induce thymidine kinase activity, regained the intact thymidine kinase peptide, and lost the ability to synthesize the shorter peptide fragment. These mutants comprise a class of animal virus mutants which have the properties expected of peptide chain termination mutants."} {"id": "PMID:172895", "title": "Evolution of type C viral genes: preservation of ancestral murine type C viral sequences in pig cellular DNA.", "content": "Domestic pigs (Sus scrofa) and other members of the family Suidae have multiple copies of type C viral gene sequences in the cellular DNA of all their tissues. Partially homologous viral gene sequences are also found in cellular DNA of rodents, particularly Muridae. The results lead to the conclusion that type C viral genes were introduced into the Suidae lineage as a result of trans-species infection by an ancestral xenotropic murine virus. The rate of evolution of the virogene sequences in the pig appears to be much slower than that of genes that have remained in the rodent lineage; this may be a consequence of transfer from a shorter-lived animal (the rodent) to a longer-lived one (the pig). We estimate the time of gene transmission as 5-10 million years ago and conclude that the present-day porcine type C virogenes most closely approximate the viral genes as they were several million years ago in the rodent lineage.", "contents": "Evolution of type C viral genes: preservation of ancestral murine type C viral sequences in pig cellular DNA. Domestic pigs (Sus scrofa) and other members of the family Suidae have multiple copies of type C viral gene sequences in the cellular DNA of all their tissues. Partially homologous viral gene sequences are also found in cellular DNA of rodents, particularly Muridae. The results lead to the conclusion that type C viral genes were introduced into the Suidae lineage as a result of trans-species infection by an ancestral xenotropic murine virus. The rate of evolution of the virogene sequences in the pig appears to be much slower than that of genes that have remained in the rodent lineage; this may be a consequence of transfer from a shorter-lived animal (the rodent) to a longer-lived one (the pig). We estimate the time of gene transmission as 5-10 million years ago and conclude that the present-day porcine type C virogenes most closely approximate the viral genes as they were several million years ago in the rodent lineage."} {"id": "PMID:172896", "title": "A unique complement derived chemotactic factor for tumor cells.", "content": "A factor chemotactic for Walker carcinosarcoma and Novikoff hepatoma tumor cells can be generated by incubation of serum with an extract from tumor cells. The chemotactic factor has no activity for neutrophilic leukocytes, and three factors chemotactic for leukocytes are not chemotactic for tumor cells. By the use of complement deficient serums as well as purified complement components, the chemotactic factor for tumor cells has been found to be a fragment of the fifth component (C5) of complement and appears to result from direct interaction of C5 with an enzyme in the extract. The chemotactic factor for tumor cells can be classified as a functionally unique fragment of C5 that may significantly influence the behavior of tumor cells in vivo.", "contents": "A unique complement derived chemotactic factor for tumor cells. A factor chemotactic for Walker carcinosarcoma and Novikoff hepatoma tumor cells can be generated by incubation of serum with an extract from tumor cells. The chemotactic factor has no activity for neutrophilic leukocytes, and three factors chemotactic for leukocytes are not chemotactic for tumor cells. By the use of complement deficient serums as well as purified complement components, the chemotactic factor for tumor cells has been found to be a fragment of the fifth component (C5) of complement and appears to result from direct interaction of C5 with an enzyme in the extract. The chemotactic factor for tumor cells can be classified as a functionally unique fragment of C5 that may significantly influence the behavior of tumor cells in vivo."} {"id": "PMID:172897", "title": "Growth and differentiation in culture of leukemic leukocytes from a patient with acute myelogenous leukemia and re-identification of type-C virus.", "content": "Conditioned medium from a culture of whole human embryo cells stimulated prolonged exponential growth in suspension culture of leukocytes from a patient with acute myelogenous leukemia. Ten to 20% of the cultured cells consistently differentiated into mature granulocytes including neutrophils, eosinophils, and basophils. The proportion of lymphocytes declined after culturing, and tests for Epstein-Barr virus antigens were negative. An abnormality of a G group chromosome was observed in some metaphases from the patient's fresh bone marrow and from the cultured leukocytes, indicating growth in vitro of leukemic cells. After 4-10 weeks in culture, a budding type-C virus was continuously released by the cultured leukocytes, predominantly by undifferentiated blast cells. This virus was originally identified in three different cultures of a peripheral blood specimen obtained at the time of diagnosis. Subsequently, this virus was identified by reverse transcriptase (RNA-dependent DNA polymerase) assays and by electron microscopy in cultured leukocytes from a bone marrow specimen obtained 14 months later from the same patient. Virus produced by cultures of both specimens was closely related, if not identical, to the woolly monkey type-C virus.", "contents": "Growth and differentiation in culture of leukemic leukocytes from a patient with acute myelogenous leukemia and re-identification of type-C virus. Conditioned medium from a culture of whole human embryo cells stimulated prolonged exponential growth in suspension culture of leukocytes from a patient with acute myelogenous leukemia. Ten to 20% of the cultured cells consistently differentiated into mature granulocytes including neutrophils, eosinophils, and basophils. The proportion of lymphocytes declined after culturing, and tests for Epstein-Barr virus antigens were negative. An abnormality of a G group chromosome was observed in some metaphases from the patient's fresh bone marrow and from the cultured leukocytes, indicating growth in vitro of leukemic cells. After 4-10 weeks in culture, a budding type-C virus was continuously released by the cultured leukocytes, predominantly by undifferentiated blast cells. This virus was originally identified in three different cultures of a peripheral blood specimen obtained at the time of diagnosis. Subsequently, this virus was identified by reverse transcriptase (RNA-dependent DNA polymerase) assays and by electron microscopy in cultured leukocytes from a bone marrow specimen obtained 14 months later from the same patient. Virus produced by cultures of both specimens was closely related, if not identical, to the woolly monkey type-C virus."} {"id": "PMID:172898", "title": "Complete translation of poliovirus RNA in a eukaryotic cell-free system.", "content": "Poliovirus RNA stimulates imcorporation of 35S from both [35S]methionine and formyl-[35S]methionyl-tRNAfMet in cell-free systems derived from HeLa cells or from poliovirus-infected HeLa cells. The largest product formed under the direction of the viral RNA is the same size as the polyprotein thought to represent translation of the entire RNA. Synthesis of this polyprotein and other large products was stimulated greatly by increasing the salt concentration during the reaction from the optimum for initiation (90 mM) to the optimum for elongation (155 mM). Only one initiation peptide could be identified, and a tryptic digest of the product contained mainly peptides that cochromatographed with peptides from authentic viral proteins. The RNA from a deletion mutant of poliovirus initiated protein synthesis at the same site used by standard RNA and programmed synthesis of an appropriately deleted set of polypeptides. The results strongly support the model of translation of poliovirus RNA from a single initiation site into a continuous polyprotein that is cleaved to form the functional proteins. It is suggested that uninfected HeLa cell extracts can carry out the cleavages of nascent polyprotein.", "contents": "Complete translation of poliovirus RNA in a eukaryotic cell-free system. Poliovirus RNA stimulates imcorporation of 35S from both [35S]methionine and formyl-[35S]methionyl-tRNAfMet in cell-free systems derived from HeLa cells or from poliovirus-infected HeLa cells. The largest product formed under the direction of the viral RNA is the same size as the polyprotein thought to represent translation of the entire RNA. Synthesis of this polyprotein and other large products was stimulated greatly by increasing the salt concentration during the reaction from the optimum for initiation (90 mM) to the optimum for elongation (155 mM). Only one initiation peptide could be identified, and a tryptic digest of the product contained mainly peptides that cochromatographed with peptides from authentic viral proteins. The RNA from a deletion mutant of poliovirus initiated protein synthesis at the same site used by standard RNA and programmed synthesis of an appropriately deleted set of polypeptides. The results strongly support the model of translation of poliovirus RNA from a single initiation site into a continuous polyprotein that is cleaved to form the functional proteins. It is suggested that uninfected HeLa cell extracts can carry out the cleavages of nascent polyprotein."} {"id": "PMID:172899", "title": "Effects of estrogen on gene expression in chick oviduct: nuclear receptor levels and initiation of transcription.", "content": "Estrogen (diethylstilbesterol) was administered in vivo to chicks for various time periods. Chromatin was then prepared from oviduct nuclei and assayed for its capacity to support initiation of RNA chain synthesis in vitro in the presence of saturating levels of Escherichia coli RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase; EC 2.7.7.6). These same nuclei were also assayed by a [3H]estradiol exchange assay for their endogenous receptor content. The number of available initiation sites for RNA synthesis on chromatin was shown to correlate with the endogenous levels of nuclear estrogen receptor. A decrease in the nuclear concentration of estrogen receptor molecules and the concentration of initiation sites for RNA synthesis occurred during withdrawal of estrogen from previously stimulated chicks. Both parameters declined with a similar half-life. When estrogen was readministered to withdrawn chicks, the number of initiation sites increased 2-fold as early as 30 min and approached a maximal level (3-fold) by 1 hr. During the same period of restimulation with estrogen, the number of estrogen receptor molecules bound to nuclei increased to a maximum at 20 min and then declined at 1 hr to a steady-state level 2-fold higher than the withdrawn chicks. Simultaneous measurements of RNA chain length and RNA chain propagation rate demonstrated that parameters remained relatively constant throughout estrogen withdrawal as well as secondary stimulation. The temporal correlation between changes in the levels of nuclear-bound estrogen receptor and the number of RNA chain initiation sites on chromatin prepared from these same nuclei strongly suggested that the hormone receptor complexes act on chromatin to mediate these changes in genetic transcriptional activity.", "contents": "Effects of estrogen on gene expression in chick oviduct: nuclear receptor levels and initiation of transcription. Estrogen (diethylstilbesterol) was administered in vivo to chicks for various time periods. Chromatin was then prepared from oviduct nuclei and assayed for its capacity to support initiation of RNA chain synthesis in vitro in the presence of saturating levels of Escherichia coli RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase; EC 2.7.7.6). These same nuclei were also assayed by a [3H]estradiol exchange assay for their endogenous receptor content. The number of available initiation sites for RNA synthesis on chromatin was shown to correlate with the endogenous levels of nuclear estrogen receptor. A decrease in the nuclear concentration of estrogen receptor molecules and the concentration of initiation sites for RNA synthesis occurred during withdrawal of estrogen from previously stimulated chicks. Both parameters declined with a similar half-life. When estrogen was readministered to withdrawn chicks, the number of initiation sites increased 2-fold as early as 30 min and approached a maximal level (3-fold) by 1 hr. During the same period of restimulation with estrogen, the number of estrogen receptor molecules bound to nuclei increased to a maximum at 20 min and then declined at 1 hr to a steady-state level 2-fold higher than the withdrawn chicks. Simultaneous measurements of RNA chain length and RNA chain propagation rate demonstrated that parameters remained relatively constant throughout estrogen withdrawal as well as secondary stimulation. The temporal correlation between changes in the levels of nuclear-bound estrogen receptor and the number of RNA chain initiation sites on chromatin prepared from these same nuclei strongly suggested that the hormone receptor complexes act on chromatin to mediate these changes in genetic transcriptional activity."} {"id": "PMID:172900", "title": "Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components.", "content": "Intact DNA molecules extracted from HSV-1 (herpes simplex virus 1, human herpes virus 1) strain MP virions have a molecular weight of approximately 97 X 10(6), but cleavage with the HinIII restriction enzyme yields fourteen fragments with summed molecular weights of 160 X 10(6). Six \"major\" fragments occur once in every molecule in the population and account for 60% of the genetic information. Four \"minor\" fragments are present in amounts equivalent to one copy for every two genomes (0.5 molar ratio) and the other four occur only once in every four molecules (0.25 molar ratio). The minor fragments can be arranged into four equimolar sets, each with summed molecular weights that account for the remaining 40% of the genome. Treatment with lambda 5' exonuclease revealed that all molecules contain 0.5 molar ratio fragments at both termini. These observations and the results of similar analyses of the EcoRI and double HinIII/EcoRI digests indicate that there are four distinct structural forms of HSV DNA which differ only in the relative orientations of two subregions, designated L and S. The L and S segments consist of 82 and 18% of the sequences, respectively, and each has inverted terminally redundant regions that correspond to the internal duplications observed by electron microscopy. The DNA from other strains of HSV-1 and 2 also consists of equal proportions of all four possible permutations of the L and S segments. These unusual features of HSV DNA molecules have novel implications with regard to the genetic map and the mode of replication and evolution of herpes simples viruses.", "contents": "Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components. Intact DNA molecules extracted from HSV-1 (herpes simplex virus 1, human herpes virus 1) strain MP virions have a molecular weight of approximately 97 X 10(6), but cleavage with the HinIII restriction enzyme yields fourteen fragments with summed molecular weights of 160 X 10(6). Six \"major\" fragments occur once in every molecule in the population and account for 60% of the genetic information. Four \"minor\" fragments are present in amounts equivalent to one copy for every two genomes (0.5 molar ratio) and the other four occur only once in every four molecules (0.25 molar ratio). The minor fragments can be arranged into four equimolar sets, each with summed molecular weights that account for the remaining 40% of the genome. Treatment with lambda 5' exonuclease revealed that all molecules contain 0.5 molar ratio fragments at both termini. These observations and the results of similar analyses of the EcoRI and double HinIII/EcoRI digests indicate that there are four distinct structural forms of HSV DNA which differ only in the relative orientations of two subregions, designated L and S. The L and S segments consist of 82 and 18% of the sequences, respectively, and each has inverted terminally redundant regions that correspond to the internal duplications observed by electron microscopy. The DNA from other strains of HSV-1 and 2 also consists of equal proportions of all four possible permutations of the L and S segments. These unusual features of HSV DNA molecules have novel implications with regard to the genetic map and the mode of replication and evolution of herpes simples viruses."} {"id": "PMID:172901", "title": "Conformational fluctuations of DNA helix.", "content": "Treatment of a homogeneous sample of circular DNA molecules that contain at least one single-strand scission per molecule with ligase yields a population of covalently closed circles heterogeneous in the topological winding number alpha. Under proper conditions, the product molecules with different values of alpha can all be resolved by gel electrophoresis. The distributions in alpha for several DNAs, covalently closed at different temperatures, have been determined and the results have been interpreted in terms of thermal fluctuations of the DNA helix.", "contents": "Conformational fluctuations of DNA helix. Treatment of a homogeneous sample of circular DNA molecules that contain at least one single-strand scission per molecule with ligase yields a population of covalently closed circles heterogeneous in the topological winding number alpha. Under proper conditions, the product molecules with different values of alpha can all be resolved by gel electrophoresis. The distributions in alpha for several DNAs, covalently closed at different temperatures, have been determined and the results have been interpreted in terms of thermal fluctuations of the DNA helix."} {"id": "PMID:172902", "title": "Translation of RNA that contains polyadenylate from yeast mitochondria in an Escherichia coli ribosomal system.", "content": "RNA that contains poly(A) [poly(A)-RNA] has been isolated from yeast mitochondria by poly(U) Sepharose-4B column chromatography. Pulse-labeled poly(A)-RNA shows 8-10 discrete peaks by acrylamide gel electrophoresis. The specific activity of mitochondrial poly(A)-RAN is six to eight times greater than that of mitochondrial rRNA after pulse labeling of protoplasts with [3H-]uridine. Ethidium bromide inhibits incorporation by over 90%. The total mitochondrial RNA preparation was contaminated with 5-15% cytoplasmic rRNA as determined by gel electrophoresis, but RNA exhaustion hybridization experiments indicated little or no cytoplasmic contamination of the mitochondrial poly(A)-RNA. The poly(A)-RNA stimulates [3H]leucine incorporation into protein in an E. coli cell-free system. A fraction of the labeled product is precipitated with antibody directed toward yeast cytochrome oxidase, but not with antibody directed toward bovine serum albumin. Sodium dodecyl sulfate gel electrophoresis of the immunoprecipitated material reveals labeled peptides having the mobility of the three larger cytochrome oxidase peptides, which are known to be translated by mitochondrial ribosomes.", "contents": "Translation of RNA that contains polyadenylate from yeast mitochondria in an Escherichia coli ribosomal system. RNA that contains poly(A) [poly(A)-RNA] has been isolated from yeast mitochondria by poly(U) Sepharose-4B column chromatography. Pulse-labeled poly(A)-RNA shows 8-10 discrete peaks by acrylamide gel electrophoresis. The specific activity of mitochondrial poly(A)-RAN is six to eight times greater than that of mitochondrial rRNA after pulse labeling of protoplasts with [3H-]uridine. Ethidium bromide inhibits incorporation by over 90%. The total mitochondrial RNA preparation was contaminated with 5-15% cytoplasmic rRNA as determined by gel electrophoresis, but RNA exhaustion hybridization experiments indicated little or no cytoplasmic contamination of the mitochondrial poly(A)-RNA. The poly(A)-RNA stimulates [3H]leucine incorporation into protein in an E. coli cell-free system. A fraction of the labeled product is precipitated with antibody directed toward yeast cytochrome oxidase, but not with antibody directed toward bovine serum albumin. Sodium dodecyl sulfate gel electrophoresis of the immunoprecipitated material reveals labeled peptides having the mobility of the three larger cytochrome oxidase peptides, which are known to be translated by mitochondrial ribosomes."} {"id": "PMID:172903", "title": "Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence.", "content": "Androgen- and estrogen-binding macromolecules from the hypothalamus plus preoptic area of 3- to 4-week-old mice have been detected and partially characterized. These components bind the respective hormones with high affinity (saturating at 4-8 nM) and sediment with rates typical of presumed steroid receptors (4.0-4.5 S in 0.15 M NaCl, 5.0-7.5 S without salt). A 90-95% reduction in androgen binding found in the androgen-insensitivity mutant mouse, testicular feminization (Tfm), provides a genetic control for the specificity of binding. This reduced androgen binding with Tfm/Y mutants and blocking experiments with non-radioactive estradiol [estra-1,3,5(10)-triene-3,17beta-diol] and testosterone (17beta-hydroxy-4-androsten-3-one) indicate the existence of at least two binding components: one with high affinity only for estradiol, the other with affinity for both androgens and estrogen. Based on these properties, a receptor mechanism that detects relative concentrations of androgens and estrogens is proposed.", "contents": "Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence. Androgen- and estrogen-binding macromolecules from the hypothalamus plus preoptic area of 3- to 4-week-old mice have been detected and partially characterized. These components bind the respective hormones with high affinity (saturating at 4-8 nM) and sediment with rates typical of presumed steroid receptors (4.0-4.5 S in 0.15 M NaCl, 5.0-7.5 S without salt). A 90-95% reduction in androgen binding found in the androgen-insensitivity mutant mouse, testicular feminization (Tfm), provides a genetic control for the specificity of binding. This reduced androgen binding with Tfm/Y mutants and blocking experiments with non-radioactive estradiol [estra-1,3,5(10)-triene-3,17beta-diol] and testosterone (17beta-hydroxy-4-androsten-3-one) indicate the existence of at least two binding components: one with high affinity only for estradiol, the other with affinity for both androgens and estrogen. Based on these properties, a receptor mechanism that detects relative concentrations of androgens and estrogens is proposed."} {"id": "PMID:172904", "title": "Requirement for cellular protein synthesis in reversal of ethidium-bormide-induced inhibition of cell transformation by murine sarcoma virus.", "content": "Cultures of mouse Balb 3T3 fibroblasts exposed to a noncytotoxic dose of ethidium bromide for 16-18 hr are unable to produce foci after infection with murine sarcoma virus. Such cultures regain susceptibility to infection when incubated for 6-8 hr in drug-free growth medium. Pretreated but not untreated cultures exhibit sensitivity toward brief (6 hr) exposure to cycloheximide, chloramphenicol, and actinomycin D before infection. Pretreatment with cordy-cepin inhibits the ability of cultures to produce foci after infection. The recovery of ethidium-bromide-treated cultures requires the synthesis of cellular proteins which may have some important role in the establishment of RNA tumor virus infection.", "contents": "Requirement for cellular protein synthesis in reversal of ethidium-bormide-induced inhibition of cell transformation by murine sarcoma virus. Cultures of mouse Balb 3T3 fibroblasts exposed to a noncytotoxic dose of ethidium bromide for 16-18 hr are unable to produce foci after infection with murine sarcoma virus. Such cultures regain susceptibility to infection when incubated for 6-8 hr in drug-free growth medium. Pretreated but not untreated cultures exhibit sensitivity toward brief (6 hr) exposure to cycloheximide, chloramphenicol, and actinomycin D before infection. Pretreatment with cordy-cepin inhibits the ability of cultures to produce foci after infection. The recovery of ethidium-bromide-treated cultures requires the synthesis of cellular proteins which may have some important role in the establishment of RNA tumor virus infection."} {"id": "PMID:172905", "title": "Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins.", "content": "The synthesis of specific nonhistone chromosomal proteins in the uterus of the ovariectomized rat was examined as a function of time after treatment with estradiol-17beta. Sequential stimulations in the rates of synthesis of at least five nonhistone chromosomal proteins having molecular weights of 96,000, 70,500, 29,400, 20,700, and 16,400, respectively, were observed. The rate of synthesis of the nonhistone chromosomal protein having a molecular weight of 70,500 was increased at 1 hr after hormone treatment. This was the first nonhistone chromosomal protein to be induced by estrogen, and its induction was blocked by pretreatment with actinomycin D. The data reported suggest but do not prove that this protein is the 4.5 S estrogen receptor, and that it is the induced nuclear acidic protein described earlier by Teng and Hamilton. The rates of synthesis of the nonhistone proteins with molecular weights of 96,000, 29,400, 20,700, and 16,400 were increased at 3,5,24, and 24 hr, respectively, after hormone treatment.", "contents": "Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins. The synthesis of specific nonhistone chromosomal proteins in the uterus of the ovariectomized rat was examined as a function of time after treatment with estradiol-17beta. Sequential stimulations in the rates of synthesis of at least five nonhistone chromosomal proteins having molecular weights of 96,000, 70,500, 29,400, 20,700, and 16,400, respectively, were observed. The rate of synthesis of the nonhistone chromosomal protein having a molecular weight of 70,500 was increased at 1 hr after hormone treatment. This was the first nonhistone chromosomal protein to be induced by estrogen, and its induction was blocked by pretreatment with actinomycin D. The data reported suggest but do not prove that this protein is the 4.5 S estrogen receptor, and that it is the induced nuclear acidic protein described earlier by Teng and Hamilton. The rates of synthesis of the nonhistone proteins with molecular weights of 96,000, 29,400, 20,700, and 16,400 were increased at 3,5,24, and 24 hr, respectively, after hormone treatment."} {"id": "PMID:172906", "title": "Thermolabile T (tumor) antigen from cells transformed by a temperature-sensitive mutant of simian virus 40.", "content": "Partially purified tumor (T) antigen from a strain of Chinese hamster lung cells transformed by wild-type simian virus 40 (SV 40) and either of two temperature-sensitive SV 40 mutants has been studied as a DNA binding protein. The DNA binding activity present in the T-antigen-containing fractions is inhibited by purified hamster anti-T IgG but not by equivalent amounts of nonimmune hamster IgG. T from either wild-type- or tsC219-transformed cells is relatively stable during heating at 44 degrees compared to T prepared from tsA239-transformed cells. These results strongly suggest that T is a product of the SV 40 A gene.", "contents": "Thermolabile T (tumor) antigen from cells transformed by a temperature-sensitive mutant of simian virus 40. Partially purified tumor (T) antigen from a strain of Chinese hamster lung cells transformed by wild-type simian virus 40 (SV 40) and either of two temperature-sensitive SV 40 mutants has been studied as a DNA binding protein. The DNA binding activity present in the T-antigen-containing fractions is inhibited by purified hamster anti-T IgG but not by equivalent amounts of nonimmune hamster IgG. T from either wild-type- or tsC219-transformed cells is relatively stable during heating at 44 degrees compared to T prepared from tsA239-transformed cells. These results strongly suggest that T is a product of the SV 40 A gene."} {"id": "PMID:172907", "title": "In vitro synthesis of a constitutive enzyme of Escherichia coli, 6-phosphogluconate dehydrogenase.", "content": "Enzymes of central intermediary metabolism are among the constitutive proteins of Escherichia coli. 6-Phosphogluconate dehydrogenase [6-phospho-D-gluconate: nicotinamide adenine dinucleotide phosphate 2-oxidoreductase (decarboxylating), EC 1.1.1.44-A1, an enzyme of the hexose monophosphate shunt, was synthesized in vitro in a coupled transcription-translation system directed by DNA from a specialized transducing phage carrying gnd, the structural gene. Enzyme synthesized in vitro was detected by radiochemical assay of its activity. Kinetic experiments using inhibitors of transcription and translation suggest that synthesis of the mRNA for the enzyme was initiated at the gnd promoter. Neither cyclic AMP nor cyclic GMP had any effect on the amount of enzyme synthesized in vitro.", "contents": "In vitro synthesis of a constitutive enzyme of Escherichia coli, 6-phosphogluconate dehydrogenase. Enzymes of central intermediary metabolism are among the constitutive proteins of Escherichia coli. 6-Phosphogluconate dehydrogenase [6-phospho-D-gluconate: nicotinamide adenine dinucleotide phosphate 2-oxidoreductase (decarboxylating), EC 1.1.1.44-A1, an enzyme of the hexose monophosphate shunt, was synthesized in vitro in a coupled transcription-translation system directed by DNA from a specialized transducing phage carrying gnd, the structural gene. Enzyme synthesized in vitro was detected by radiochemical assay of its activity. Kinetic experiments using inhibitors of transcription and translation suggest that synthesis of the mRNA for the enzyme was initiated at the gnd promoter. Neither cyclic AMP nor cyclic GMP had any effect on the amount of enzyme synthesized in vitro."} {"id": "PMID:172908", "title": "Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro.", "content": "Clonal isolates of mouse 3T3 cells and primary rat embryo cells, recovered nonselectively after infection by simian virus 40 (SV40), have been tested for tumorigenicity in the immune-deficient nude mice in order to determine the cellular growth properties in vitro specifically correlated with neoplastic growth in vivo. In addition, mouse 3T3 cells transformed by murine sarcoma virus (MuSV, Kirsten strain), and revertants isolated from cells fully transformed by either SV40 or MuSV were also studied. Results suggest that the single cellular property consistently associated with tumorigenicity in nude mice is the acquisition by virus-transformed cells of the ability to proliferate in vitro in the absence of anchorage. Other cellular parameters of virus-induced transformation, such as lack of sensitivity to high cell density and the capacity to grow in low serum concentration, are dissociable from cellular tumorigeneicity. This conclusion is supported further by the demonstration that specific selection in vivo for tumorigenic cells from anchorage-dependent cells results in the isolation of anchorage-independent cells. Conversely, a single-step selection in vitro for anchorage-independent cells from nontumorigenic cells results in a simultaneous selection of highly tumorigenic subclones.", "contents": "Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Clonal isolates of mouse 3T3 cells and primary rat embryo cells, recovered nonselectively after infection by simian virus 40 (SV40), have been tested for tumorigenicity in the immune-deficient nude mice in order to determine the cellular growth properties in vitro specifically correlated with neoplastic growth in vivo. In addition, mouse 3T3 cells transformed by murine sarcoma virus (MuSV, Kirsten strain), and revertants isolated from cells fully transformed by either SV40 or MuSV were also studied. Results suggest that the single cellular property consistently associated with tumorigenicity in nude mice is the acquisition by virus-transformed cells of the ability to proliferate in vitro in the absence of anchorage. Other cellular parameters of virus-induced transformation, such as lack of sensitivity to high cell density and the capacity to grow in low serum concentration, are dissociable from cellular tumorigeneicity. This conclusion is supported further by the demonstration that specific selection in vivo for tumorigenic cells from anchorage-dependent cells results in the isolation of anchorage-independent cells. Conversely, a single-step selection in vitro for anchorage-independent cells from nontumorigenic cells results in a simultaneous selection of highly tumorigenic subclones."} {"id": "PMID:172909", "title": "Deposition of histones onto replicating chromosomes.", "content": "The mode of distribution of newly synthesized and pre-existing histones has been studied during the process of chromosome replication. Newly synthesized histone was labeled with [3H]lysine and newly synthesized DNA was density labeled with iododeoxyuridine. The histone was covalently linked to DNA, and radiolabeled histone was analyzed on CsCl density gradients. We have defined conditions that do not give rise to histone randomization during isolation, and also developed a method of defining the distribution of histones in chromatin on a density gradient in the unavoidable presence of nonhistone protein. Three possible modes of distribution of histone onto the replicating chromosome can be conceived; we describe experiments designed to distinguish unequivocally among these possibilities and conclude that histones are deposited randomly onto the chromosome.", "contents": "Deposition of histones onto replicating chromosomes. The mode of distribution of newly synthesized and pre-existing histones has been studied during the process of chromosome replication. Newly synthesized histone was labeled with [3H]lysine and newly synthesized DNA was density labeled with iododeoxyuridine. The histone was covalently linked to DNA, and radiolabeled histone was analyzed on CsCl density gradients. We have defined conditions that do not give rise to histone randomization during isolation, and also developed a method of defining the distribution of histones in chromatin on a density gradient in the unavoidable presence of nonhistone protein. Three possible modes of distribution of histone onto the replicating chromosome can be conceived; we describe experiments designed to distinguish unequivocally among these possibilities and conclude that histones are deposited randomly onto the chromosome."} {"id": "PMID:172910", "title": "Rous sarcoma virus activates embryonic globin genes in chicken fibroblasts.", "content": "Complementary DNA (cDNA) specific for chick globin mRNA sequences fails to hybridize to total RNA extracted from chicken fibroblasts. After infection by Rous sarcoma virus, RNA complementary to globin cDNA is detectable in 100-500 copies per cell. Infection of fibroblasts with the transformation defective (td) deletion mutant of Rous sarcoma virus leads to normal virus production, but not to host cell transformation or accumulation of RNA sequences complementary to globin cDNA. Our evidence shows that the globin genes activated by Rous sarcoma virus are those specified by embryonic chick red cells; adult-specific globin sequences were not detected.", "contents": "Rous sarcoma virus activates embryonic globin genes in chicken fibroblasts. Complementary DNA (cDNA) specific for chick globin mRNA sequences fails to hybridize to total RNA extracted from chicken fibroblasts. After infection by Rous sarcoma virus, RNA complementary to globin cDNA is detectable in 100-500 copies per cell. Infection of fibroblasts with the transformation defective (td) deletion mutant of Rous sarcoma virus leads to normal virus production, but not to host cell transformation or accumulation of RNA sequences complementary to globin cDNA. Our evidence shows that the globin genes activated by Rous sarcoma virus are those specified by embryonic chick red cells; adult-specific globin sequences were not detected."} {"id": "PMID:172911", "title": "Cytochemical study of secretory process in transplantable insulinoma of syrian golden hamster.", "content": "Electron microscopy, including phosphatase cytochemistry, indicates that the secretory granules of an insulinoma producing proinsulin and insulin are packaged by the endoplasmic reticulum (ER) and especially by a specialized region of ER which we call GERL because of the spatial relationship of this region to the Golgi apparatus and its apparent role in producing lysosomes. The granules are not derived from the Golgi apparatus. Preliminary evidence suggests this may be true also of pancreatic beta-cells.", "contents": "Cytochemical study of secretory process in transplantable insulinoma of syrian golden hamster. Electron microscopy, including phosphatase cytochemistry, indicates that the secretory granules of an insulinoma producing proinsulin and insulin are packaged by the endoplasmic reticulum (ER) and especially by a specialized region of ER which we call GERL because of the spatial relationship of this region to the Golgi apparatus and its apparent role in producing lysosomes. The granules are not derived from the Golgi apparatus. Preliminary evidence suggests this may be true also of pancreatic beta-cells."} {"id": "PMID:172912", "title": "Relationship in nucleic acid sequences between mouse mammary tumor virus variants.", "content": "Primary cultures of mouse mammary carcinomas were used as a source of both radioactively labeled and unlabeled 60-70S RNA of mouse mammary tumor virus (MMTV) obtained from various mouse strains. Competition molecular hybridization experiments revealed that, within the limits of the assay, the RNAs of the MMTVs synthesized in culture by the tumors of the mouse strains RIII, GR, A, and C3H, are identical. A comparison of the genomes of the milk-transmitted MMTV(C3H) and the vertically transmitted MMTV(C3Hf) revealed that these two viruses are approximately 75% similar. No nucleic acid sequence homology was observed between MMTV(C3H) 60-70S RNA and the RNAs of murine leukemia virus, Mason-Pfizer virus, or the BrdUrd-induced type-B quinea pig virus.", "contents": "Relationship in nucleic acid sequences between mouse mammary tumor virus variants. Primary cultures of mouse mammary carcinomas were used as a source of both radioactively labeled and unlabeled 60-70S RNA of mouse mammary tumor virus (MMTV) obtained from various mouse strains. Competition molecular hybridization experiments revealed that, within the limits of the assay, the RNAs of the MMTVs synthesized in culture by the tumors of the mouse strains RIII, GR, A, and C3H, are identical. A comparison of the genomes of the milk-transmitted MMTV(C3H) and the vertically transmitted MMTV(C3Hf) revealed that these two viruses are approximately 75% similar. No nucleic acid sequence homology was observed between MMTV(C3H) 60-70S RNA and the RNAs of murine leukemia virus, Mason-Pfizer virus, or the BrdUrd-induced type-B quinea pig virus."} {"id": "PMID:172913", "title": "Separation of sarcoma virus-specific and leukemia virus-specific genetic sequences of Moloney sarcoma virus.", "content": "We have studied the nucleic acid sequences in nonproducer cells transformed by Moloney sarcoma virus or Abelson leukemia virus (two types of replication-defective, RNA-containing, viruses isolated by passage of Moloney leukemia virus in BALB/c mice). DNA probes from the Moloney leukemia in virus detect RNA in both Abelson virus-transformed nonproducer cells and Moloney sarcoma virus-transformed nonproducer cells. A sarcoma-specific cDNA, prepared from the Moloney sarcoma virus, has extensive homology to RNA found in heterologous nonproducer cells transformed by Moloney sarcoma virus, has little homology to RNA in cells producing Moloney leukemia virus, and no detectable homology to RNA in nonproducer cells transformed by the Abelson virus. By analogy to earlier data on avian and mammalian sarcoma viruses, these results suggest that the Moloney sarcoma virus arose by recombination between a portion of the Moloney leukemia virus genome and additional sarcoma-specific information, and indicate that the expression of this information in not essential for Abelson virus-mediated fibroblast transformation.", "contents": "Separation of sarcoma virus-specific and leukemia virus-specific genetic sequences of Moloney sarcoma virus. We have studied the nucleic acid sequences in nonproducer cells transformed by Moloney sarcoma virus or Abelson leukemia virus (two types of replication-defective, RNA-containing, viruses isolated by passage of Moloney leukemia virus in BALB/c mice). DNA probes from the Moloney leukemia in virus detect RNA in both Abelson virus-transformed nonproducer cells and Moloney sarcoma virus-transformed nonproducer cells. A sarcoma-specific cDNA, prepared from the Moloney sarcoma virus, has extensive homology to RNA found in heterologous nonproducer cells transformed by Moloney sarcoma virus, has little homology to RNA in cells producing Moloney leukemia virus, and no detectable homology to RNA in nonproducer cells transformed by the Abelson virus. By analogy to earlier data on avian and mammalian sarcoma viruses, these results suggest that the Moloney sarcoma virus arose by recombination between a portion of the Moloney leukemia virus genome and additional sarcoma-specific information, and indicate that the expression of this information in not essential for Abelson virus-mediated fibroblast transformation."} {"id": "PMID:172922", "title": "NMR in cancer: IX. The concept of cancer treatment by NMR: a preliminary report of high resolution NMR or phosphorus in normal and malignant tissues.", "content": "A preliminary study of high resolution P31 nuclear resonance of normal and malignant tissue is reported. Utilization of nuclear resonance in the frequency frame contrasts with the pulsed magnetic resonance studies originally introduced for investigating cancer. Frequency dependent NMR was employed to study cancer with the primary objective of identifying resonant frequencies that could be used to indicate cancer. Such cancer specific frequencies would help circumvent current difficulties in the pulsed resonance diagnosis of cancer and might even have application in therapy.", "contents": "NMR in cancer: IX. The concept of cancer treatment by NMR: a preliminary report of high resolution NMR or phosphorus in normal and malignant tissues. A preliminary study of high resolution P31 nuclear resonance of normal and malignant tissue is reported. Utilization of nuclear resonance in the frequency frame contrasts with the pulsed magnetic resonance studies originally introduced for investigating cancer. Frequency dependent NMR was employed to study cancer with the primary objective of identifying resonant frequencies that could be used to indicate cancer. Such cancer specific frequencies would help circumvent current difficulties in the pulsed resonance diagnosis of cancer and might even have application in therapy."} {"id": "PMID:172923", "title": "Some aspects of ACTH action on cerebral metabolism in infant rats.", "content": "In 150 newborn rats of either sex the influence of ACTH on cerebral phospholipid, phosphoprotein, and nucleic acids metabolism was investigated. The results show that ACTH induces a great stimulation of the cerebral phospholipid metabolism, especially in 14-and 21-day-old rats, a significant increase in the phosphoprotein metabolism at 7 and 14 days after birth, and a stimulation of the RNA synthesis in 7- and 14-day-old rats. The significance of these results is discussed.", "contents": "Some aspects of ACTH action on cerebral metabolism in infant rats. In 150 newborn rats of either sex the influence of ACTH on cerebral phospholipid, phosphoprotein, and nucleic acids metabolism was investigated. The results show that ACTH induces a great stimulation of the cerebral phospholipid metabolism, especially in 14-and 21-day-old rats, a significant increase in the phosphoprotein metabolism at 7 and 14 days after birth, and a stimulation of the RNA synthesis in 7- and 14-day-old rats. The significance of these results is discussed."} {"id": "PMID:172924", "title": "Effects of 2200-m hypoxia on glucidic metabolism.", "content": "Rats exposed for different intervals (1, 3 and 6 hours, the first day, and then 6 hours a day for 9 days) to a 2200-m hypoxia presented metabolic changes demonstrating an anaerobic glucose utilization. Thus, in accordance with other authors, at different depressurization values the liver homogenate had increased lactate and pyruvate concentrations, decreased NAD and NADH2 concentrations and a decreased ATP formation, demonstrating the inefficient glucide metabolization. These modifications were evident in the first hours of depressurization, but did not occur under acclimatization during the 9 days of exposure. The LDH concentration remained practically unchanged, which might be explained by its explained by its excessive presence in relation to the normal exercise solicitation. A urinary hypercompensatory alkalinization was also recorded.", "contents": "Effects of 2200-m hypoxia on glucidic metabolism. Rats exposed for different intervals (1, 3 and 6 hours, the first day, and then 6 hours a day for 9 days) to a 2200-m hypoxia presented metabolic changes demonstrating an anaerobic glucose utilization. Thus, in accordance with other authors, at different depressurization values the liver homogenate had increased lactate and pyruvate concentrations, decreased NAD and NADH2 concentrations and a decreased ATP formation, demonstrating the inefficient glucide metabolization. These modifications were evident in the first hours of depressurization, but did not occur under acclimatization during the 9 days of exposure. The LDH concentration remained practically unchanged, which might be explained by its explained by its excessive presence in relation to the normal exercise solicitation. A urinary hypercompensatory alkalinization was also recorded."} {"id": "PMID:172925", "title": "Increases in paradoxical sleep as a result of amygdaloid stimulation.", "content": "Holtzman rats were partially and selectively deprived of paradoxical sleep (PS) for a 16 1/2 hr period and allowed to rest for a 7 1/2 hr period each day. Test animals were given mild (60 Hz, 50 muA) unilateral amygdaloid stimulation for one min each day of a 5 day test period. There was a significant increase in PS during the rest periods of test animals on stimulation days when compared to nonstimulated controls. The effect did not last beyond a 5 day period. Only subconvulsive behaviour was observed in two test animals. The similarity to the PS increases in this study to those seen in conventional learning and other stiuations are discussed.", "contents": "Increases in paradoxical sleep as a result of amygdaloid stimulation. Holtzman rats were partially and selectively deprived of paradoxical sleep (PS) for a 16 1/2 hr period and allowed to rest for a 7 1/2 hr period each day. Test animals were given mild (60 Hz, 50 muA) unilateral amygdaloid stimulation for one min each day of a 5 day test period. There was a significant increase in PS during the rest periods of test animals on stimulation days when compared to nonstimulated controls. The effect did not last beyond a 5 day period. Only subconvulsive behaviour was observed in two test animals. The similarity to the PS increases in this study to those seen in conventional learning and other stiuations are discussed."} {"id": "PMID:172926", "title": "Response of the adrenals to stress in animals from litters with different numbers of young.", "content": "Undernutrition and overnutrition during the suckling period -- achieved by adjusting the number of infant rats per litter to 4, 8 and 14 -- resulted in a decrease in the plasma corticosterone level and in corticosterone production by the adrenals in vitro in overfed animals at the age of 30, 180 and 300--360 days. An enhanced response to ether anaesthesia or immobilization stress was found in overfed animals from the smallest litters. The results show that a change in postnatal nutrition and in social relationships in the litter influences maturation of the hypoathalamo-hypophysio-adrenal regulatory system; in adulthood this is manifested in changes in production of the adrenal hormones and in the reaction of the adrenals to stress.", "contents": "Response of the adrenals to stress in animals from litters with different numbers of young. Undernutrition and overnutrition during the suckling period -- achieved by adjusting the number of infant rats per litter to 4, 8 and 14 -- resulted in a decrease in the plasma corticosterone level and in corticosterone production by the adrenals in vitro in overfed animals at the age of 30, 180 and 300--360 days. An enhanced response to ether anaesthesia or immobilization stress was found in overfed animals from the smallest litters. The results show that a change in postnatal nutrition and in social relationships in the litter influences maturation of the hypoathalamo-hypophysio-adrenal regulatory system; in adulthood this is manifested in changes in production of the adrenal hormones and in the reaction of the adrenals to stress."} {"id": "PMID:172927", "title": "Community mental health myths and the fate of former hospitalized patients.", "content": "This paper addresses one of these important emerging problems--the fate of former hospitalized patients--and the policy issues that the problem raises. The discussion is derived from observations of the experience of the mental health system in the State of Hawaii, but the issues raised are of relevance to other states as well.", "contents": "Community mental health myths and the fate of former hospitalized patients. This paper addresses one of these important emerging problems--the fate of former hospitalized patients--and the policy issues that the problem raises. The discussion is derived from observations of the experience of the mental health system in the State of Hawaii, but the issues raised are of relevance to other states as well."} {"id": "PMID:172928", "title": "Factor analysis of objective and subjective characteristics of a night's sleep.", "content": "Factor analysis was performed on objectively measured and subjectively reported characteristics of 46 nights' sleep in four healthy male subjects. The fragmentation of sleep by awakenings during the night, the delay before falling asleep, the total duration of sleep, and the amount of delta-wave sleep formed the bases of four separate factors.", "contents": "Factor analysis of objective and subjective characteristics of a night's sleep. Factor analysis was performed on objectively measured and subjectively reported characteristics of 46 nights' sleep in four healthy male subjects. The fragmentation of sleep by awakenings during the night, the delay before falling asleep, the total duration of sleep, and the amount of delta-wave sleep formed the bases of four separate factors."} {"id": "PMID:172929", "title": "Neuroendocrine effects of haloperidol therapy in chronic schizophrenia.", "content": "The neuroendocrine effects of haloperidol therapy have been examined in 62 male chronic schizophrenic patients, aged 16-62 years. The duration of the disease varied between 2 and 29 years. The patients were divided into 48 hebephrenics with onset of the disease at puberty, or immediately after puberty, and 14 paranoids with onset of the disease in adulthood. They received 6 mg i.m.p.d. of haloperidol, for 30 days, up to a total dose of 180 mg. The following hormonal variables were examined before therapy and at 10-20 and 30 days of treatment: total urinary gonadotropins, serum FSH and LH, GH response to insulin stimulation, ACTH reserve (Metyrapone test), total urinary 17-ketosteroids and 17-hydroxycorticoids before and after an ACTH stimulation test, serum testosterone, insulin response to glucose load, plasma thyroxine before and after a TSH stimulation test. The basic hormonal values revealed decreased secretion of total gonadotropins, FSH, LH, ACTH and testosterone, and increased insulin secretion. The haloperidol therapy seemed to stimulate the secretion of FSH, LH, total gonadotropins, ACTH and testosterone, up to normal or low-normal levels. No modifications were observed in the other hormonal variables. The significance of these results is discussed.", "contents": "Neuroendocrine effects of haloperidol therapy in chronic schizophrenia. The neuroendocrine effects of haloperidol therapy have been examined in 62 male chronic schizophrenic patients, aged 16-62 years. The duration of the disease varied between 2 and 29 years. The patients were divided into 48 hebephrenics with onset of the disease at puberty, or immediately after puberty, and 14 paranoids with onset of the disease in adulthood. They received 6 mg i.m.p.d. of haloperidol, for 30 days, up to a total dose of 180 mg. The following hormonal variables were examined before therapy and at 10-20 and 30 days of treatment: total urinary gonadotropins, serum FSH and LH, GH response to insulin stimulation, ACTH reserve (Metyrapone test), total urinary 17-ketosteroids and 17-hydroxycorticoids before and after an ACTH stimulation test, serum testosterone, insulin response to glucose load, plasma thyroxine before and after a TSH stimulation test. The basic hormonal values revealed decreased secretion of total gonadotropins, FSH, LH, ACTH and testosterone, and increased insulin secretion. The haloperidol therapy seemed to stimulate the secretion of FSH, LH, total gonadotropins, ACTH and testosterone, up to normal or low-normal levels. No modifications were observed in the other hormonal variables. The significance of these results is discussed."} {"id": "PMID:172930", "title": "Human sleep during chronic morphine intoxication.", "content": "The sleep of 6 opiate addicts was studied for 11 nights during 3 phases of a chronic morphine cycle. The control phase consisted of 5 consecutive nights before morphine administration. The induction phase consisted of 1 night at 21-36 days after the onset of morphine administration, when the daily dose was 140-220 mg. The stable dose phase consisted of 5 consecutive nights after the subjects had received 240 mg of morphine daily for 8-19 weeks. No sleep could be studied during the withdrawal phase. Sleep was continuously monitored with EEG, EMG and EOG. Chronic morphine produces signs of a small but persistent sleep disturbance: delta sleep (early night) becomes less stable and shifts toward later in the night, waking state increases during the middle of the night, RME sleep (expecially its activated EEG without eye movements) decreases, the RMES cycle increases, and burst of delta activity (with mean duration of 5-6 sec) increase. Although this disturbance persists throughout the night, it is much less than that seen after single doses of morphine in a previous study. With chronic morphine, therefore, partial tolerance develops to the sleep disturbance produced by morphine. The small but persistent nocturnal arousal during chronic morphine contrasts with the sedation seen during chronic methadone. Both opioids produce an increase in delta bursts during chronic administration, which might be an EEG phenomenon specific to chronic opioid intake.", "contents": "Human sleep during chronic morphine intoxication. The sleep of 6 opiate addicts was studied for 11 nights during 3 phases of a chronic morphine cycle. The control phase consisted of 5 consecutive nights before morphine administration. The induction phase consisted of 1 night at 21-36 days after the onset of morphine administration, when the daily dose was 140-220 mg. The stable dose phase consisted of 5 consecutive nights after the subjects had received 240 mg of morphine daily for 8-19 weeks. No sleep could be studied during the withdrawal phase. Sleep was continuously monitored with EEG, EMG and EOG. Chronic morphine produces signs of a small but persistent sleep disturbance: delta sleep (early night) becomes less stable and shifts toward later in the night, waking state increases during the middle of the night, RME sleep (expecially its activated EEG without eye movements) decreases, the RMES cycle increases, and burst of delta activity (with mean duration of 5-6 sec) increase. Although this disturbance persists throughout the night, it is much less than that seen after single doses of morphine in a previous study. With chronic morphine, therefore, partial tolerance develops to the sleep disturbance produced by morphine. The small but persistent nocturnal arousal during chronic morphine contrasts with the sedation seen during chronic methadone. Both opioids produce an increase in delta bursts during chronic administration, which might be an EEG phenomenon specific to chronic opioid intake."} {"id": "PMID:172936", "title": "Studies of vitamin D deficiency in man.", "content": "Highly sensitive assays have been developed that enable 25-hydroxycholecalciferol (25-hydroxyvitamin D3) and 25-hydroxyergocalciferol (25-hydroxyvitamin D2) to be measured in the same serum sample. With these assays it has been shown that endogenously produced cholecalciferol (vitamin D3) is important in man; the findings further emphasize the role of vitamin D metabolites as hormones rather than vitamins in the traditional sense. Dietary sources of vitamin D appear to be inadequate and vitamin D deficiency has been shown to the cause of rickets and osteomalacia in Asian immigrants to Britain. This condition may be readily treated with small doses of vitamin D. In addition, sub-clinical deficiency was found in the Asian community. In the elderly, also, vitamin D deficiency was established as an important cause of osteomalacia and again evidence for the existence of a sub-clinical deficiency state was found. It is therefore suggested that the present prophylactic practices should be reviewed. Secondary hyperparathyroidism (reflected by elevated concentrations of circulating immunoassayable parathyroid hormone) was shown to be the rule rather than the exception in vitamin D deficiency. Some patients, however, had failed to respond to a hypocalcaemic stimulus. In others, there were high concentrations of parathyroid hormone despite normal serum calcium concentrations. Thus the relationship between parathyroid hormone and metabolites of vitamin D may not be mediated through changes in serum calcium alone, and it is postulated that metabolites of vitamin D may directly affect the secretion of parathyroid hormone.", "contents": "Studies of vitamin D deficiency in man. Highly sensitive assays have been developed that enable 25-hydroxycholecalciferol (25-hydroxyvitamin D3) and 25-hydroxyergocalciferol (25-hydroxyvitamin D2) to be measured in the same serum sample. With these assays it has been shown that endogenously produced cholecalciferol (vitamin D3) is important in man; the findings further emphasize the role of vitamin D metabolites as hormones rather than vitamins in the traditional sense. Dietary sources of vitamin D appear to be inadequate and vitamin D deficiency has been shown to the cause of rickets and osteomalacia in Asian immigrants to Britain. This condition may be readily treated with small doses of vitamin D. In addition, sub-clinical deficiency was found in the Asian community. In the elderly, also, vitamin D deficiency was established as an important cause of osteomalacia and again evidence for the existence of a sub-clinical deficiency state was found. It is therefore suggested that the present prophylactic practices should be reviewed. Secondary hyperparathyroidism (reflected by elevated concentrations of circulating immunoassayable parathyroid hormone) was shown to be the rule rather than the exception in vitamin D deficiency. Some patients, however, had failed to respond to a hypocalcaemic stimulus. In others, there were high concentrations of parathyroid hormone despite normal serum calcium concentrations. Thus the relationship between parathyroid hormone and metabolites of vitamin D may not be mediated through changes in serum calcium alone, and it is postulated that metabolites of vitamin D may directly affect the secretion of parathyroid hormone."} {"id": "PMID:172937", "title": "Gastric ulcer and cancer.", "content": "The incidence of gastric carcinoma was studied in a series of 210 patients presenting with apparently benign gastric ulcer. In eight cases (3.9 per cent), carcinoma was diagnosed within 18 months and was almost certainly present from the outset; in 2.4 per cent the diagnosis was delayed for over three months, and the five-year death-rate due to gastric carcinoma was 3.2 per cent. In a mean follow-up period of 5.7 years after the first diagnosis of an ulcer (8.2 years after first symptoms), three fresh cases of gastric carcinoma were found, and in two of these the cancer was at a different site from the ulcer. The five-year incidence of fresh gastric carcinoma was 0.6 per cent. Unsuspected superficial spreading carcinoma was detected by histology in 5.4 per cent of gastrectomy specimens. The significance of these findings is discussed in relation to the management of gastric ulcer and the early diagnosis of cancer.", "contents": "Gastric ulcer and cancer. The incidence of gastric carcinoma was studied in a series of 210 patients presenting with apparently benign gastric ulcer. In eight cases (3.9 per cent), carcinoma was diagnosed within 18 months and was almost certainly present from the outset; in 2.4 per cent the diagnosis was delayed for over three months, and the five-year death-rate due to gastric carcinoma was 3.2 per cent. In a mean follow-up period of 5.7 years after the first diagnosis of an ulcer (8.2 years after first symptoms), three fresh cases of gastric carcinoma were found, and in two of these the cancer was at a different site from the ulcer. The five-year incidence of fresh gastric carcinoma was 0.6 per cent. Unsuspected superficial spreading carcinoma was detected by histology in 5.4 per cent of gastrectomy specimens. The significance of these findings is discussed in relation to the management of gastric ulcer and the early diagnosis of cancer."} {"id": "PMID:172938", "title": "Causes of death in fulminant hepatic failure and relationship to quantitative histological assessment of parenchymal damage.", "content": "The clinical course and causes of death in 132 consecutive patients with fulminant hepatic failure and grade III or IV encephalopathy have been reviewed. 105 patients died and in 96 of these an autopsy examination was performed. In 36 patients there was cerebral oedema and the mean age of this group was significantly younger than the other fatal cases. In 28 patients death was attributed to major haemorrhage which originated in the gastrointestinal tract in 25. The prothrombin time ratio was not significantly greater in patients with major bleeding than in those without but they did have a significantly lower platelet count. Sepsis contributed to death in 12 patients. In 25 patients massive hepatic necrosis only was found at autopsy and death was considered to be due solely to hepatic failure. The degree of hepatocyte loss was assessed in 80 fatal cases by a histological morphometric technique on a needle specimen of liver taken immediately post-mortem. The proportion of the liver volume occupied by hepatocytes (hepatocyte volume fraction, HVF) was greatly reduced in all patients (normal 85+/-SD 5 percent) but the mean value was significantly higher in the patients dying with sepsis, cerebral oedema or haemorrhage than in the group in whom death was attributed solely to hepatic failure. There were ten patients in whom liver function was improving at the time of death which was due to cerebral (9) or haemorrhage (1). These observations suggest that many patients presently dying from fulminant hepatic failure may be expected to survive, once more effective therapy is available for the complications of the illness.", "contents": "Causes of death in fulminant hepatic failure and relationship to quantitative histological assessment of parenchymal damage. The clinical course and causes of death in 132 consecutive patients with fulminant hepatic failure and grade III or IV encephalopathy have been reviewed. 105 patients died and in 96 of these an autopsy examination was performed. In 36 patients there was cerebral oedema and the mean age of this group was significantly younger than the other fatal cases. In 28 patients death was attributed to major haemorrhage which originated in the gastrointestinal tract in 25. The prothrombin time ratio was not significantly greater in patients with major bleeding than in those without but they did have a significantly lower platelet count. Sepsis contributed to death in 12 patients. In 25 patients massive hepatic necrosis only was found at autopsy and death was considered to be due solely to hepatic failure. The degree of hepatocyte loss was assessed in 80 fatal cases by a histological morphometric technique on a needle specimen of liver taken immediately post-mortem. The proportion of the liver volume occupied by hepatocytes (hepatocyte volume fraction, HVF) was greatly reduced in all patients (normal 85+/-SD 5 percent) but the mean value was significantly higher in the patients dying with sepsis, cerebral oedema or haemorrhage than in the group in whom death was attributed solely to hepatic failure. There were ten patients in whom liver function was improving at the time of death which was due to cerebral (9) or haemorrhage (1). These observations suggest that many patients presently dying from fulminant hepatic failure may be expected to survive, once more effective therapy is available for the complications of the illness."} {"id": "PMID:172939", "title": "Heat-accelerated radioinactivation of attenuated poliovirus.", "content": "Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment.", "contents": "Heat-accelerated radioinactivation of attenuated poliovirus. Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment."} {"id": "PMID:172940", "title": "Triplet state population study in relation to the aggregation of proflavine in frozen solutions.", "content": "The evolution of the proflavine triplet state population with the extent of aggregation is examines, by ESRmeasurements, as a function of organic solvents and mineral salts, well known for their ability to influence the aggregation process. The intensity of the triplet state population has also been investigated as a function of pH. The insertion of aromatic molecules like DNA's nucleotides between dye molecules is shown to increase the intensity of the triplet state. It is put forward that the observed triplet state is characteristic of the singly protonated proflavine which seems to be the active species in in vivo experiments.", "contents": "Triplet state population study in relation to the aggregation of proflavine in frozen solutions. The evolution of the proflavine triplet state population with the extent of aggregation is examines, by ESRmeasurements, as a function of organic solvents and mineral salts, well known for their ability to influence the aggregation process. The intensity of the triplet state population has also been investigated as a function of pH. The insertion of aromatic molecules like DNA's nucleotides between dye molecules is shown to increase the intensity of the triplet state. It is put forward that the observed triplet state is characteristic of the singly protonated proflavine which seems to be the active species in in vivo experiments."} {"id": "PMID:172946", "title": "Herpes genitalis in guinea-pigs. I. Kinetic study in infection with Herpesvirus hominis type 2.", "content": "The kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24-48 hours post infection. Virus was first isolated from the spinal cord 48-72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread.", "contents": "Herpes genitalis in guinea-pigs. I. Kinetic study in infection with Herpesvirus hominis type 2. The kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24-48 hours post infection. Virus was first isolated from the spinal cord 48-72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread."} {"id": "PMID:172947", "title": "Herpes genitalis in guinea-pigs. II. Morphological studies in female guinea-pigs infected with Herpesvirus hominis type 2.", "content": "Gross and microscopial morphological changes developing in female guinea-pigs after vaginal infection with HVH 2/Angelotti were studied. In the mucosa of the external genital tract there were inflammatory changes with formation of intra-epithelial vesicles, erosions and ulcerations. In the late stages of the infection signs of inflammatory dysplasia were also observed. The infection spread into the nervous system and produced characteristic inflammatory changes. The inflammation began as a bilateral posterior myelitis and ascended in the course of infection through the upper spinal-cord towards the brain-stem. The morphological changes were preceded by increased virus replication in the respective tissues and were correlated in time with clinical symptoms. The morphological changes seen at the site of inoculation in the external genital tract of the guinea-pig bore a certain resemblance to those seen in some cases of human infection with the same type of virus.", "contents": "Herpes genitalis in guinea-pigs. II. Morphological studies in female guinea-pigs infected with Herpesvirus hominis type 2. Gross and microscopial morphological changes developing in female guinea-pigs after vaginal infection with HVH 2/Angelotti were studied. In the mucosa of the external genital tract there were inflammatory changes with formation of intra-epithelial vesicles, erosions and ulcerations. In the late stages of the infection signs of inflammatory dysplasia were also observed. The infection spread into the nervous system and produced characteristic inflammatory changes. The inflammation began as a bilateral posterior myelitis and ascended in the course of infection through the upper spinal-cord towards the brain-stem. The morphological changes were preceded by increased virus replication in the respective tissues and were correlated in time with clinical symptoms. The morphological changes seen at the site of inoculation in the external genital tract of the guinea-pig bore a certain resemblance to those seen in some cases of human infection with the same type of virus."} {"id": "PMID:172948", "title": "In vivo studies of parainfluenza I (6/94) virus: mononuclear cell interactions.", "content": "Adsorption to and penetration of migratory mononuclear cells in vivo by Para-influenza I (6/94) virus were documented by electron microscopy during the acute phase of an experimental meningoencephalitis in ICR mice. Phagocytosis of virions was the apparent and predominant mode of viral entry into these cells. Penetration by fusion was also seen. Nucleocapsids were replicated by the mononuclear cells which became a potential reservoir for the further spread of virus.", "contents": "In vivo studies of parainfluenza I (6/94) virus: mononuclear cell interactions. Adsorption to and penetration of migratory mononuclear cells in vivo by Para-influenza I (6/94) virus were documented by electron microscopy during the acute phase of an experimental meningoencephalitis in ICR mice. Phagocytosis of virions was the apparent and predominant mode of viral entry into these cells. Penetration by fusion was also seen. Nucleocapsids were replicated by the mononuclear cells which became a potential reservoir for the further spread of virus."} {"id": "PMID:172949", "title": "Infection of guinea-pig embryo cells with varicella-zoster virus.", "content": "Varicella-zoster (VZ) virus has been shown to replicate in guinea-pig embryo (GPE) cells. When cell-free virus inocula were used, no infectious virus was liberated from these cells, either by freezing-thawing or ultrasonic disruption. However, cell-free virus was separated from GPE cells inoculated with infected human embryonic lung (HEL) cells.", "contents": "Infection of guinea-pig embryo cells with varicella-zoster virus. Varicella-zoster (VZ) virus has been shown to replicate in guinea-pig embryo (GPE) cells. When cell-free virus inocula were used, no infectious virus was liberated from these cells, either by freezing-thawing or ultrasonic disruption. However, cell-free virus was separated from GPE cells inoculated with infected human embryonic lung (HEL) cells."} {"id": "PMID:172950", "title": "Experimental immunosuppression induced by herpes simplex virus.", "content": "Cell-mediated immune response was studied in experimental herpetic infection in mice. Our data suggest that herpes simplex virus induced immunosuppression in mice. This depression was documented by the unresponsiveness of the lymphocytes to PHA stimulation in vitro and by the enhanced susceptibility of adult mice to Coxsackie B virus infection. Our data also suggest that levamisole, a potent immunostimulant drug, had no effect on the unresponsiveness of the lymphocytes to PHA stimulation.", "contents": "Experimental immunosuppression induced by herpes simplex virus. Cell-mediated immune response was studied in experimental herpetic infection in mice. Our data suggest that herpes simplex virus induced immunosuppression in mice. This depression was documented by the unresponsiveness of the lymphocytes to PHA stimulation in vitro and by the enhanced susceptibility of adult mice to Coxsackie B virus infection. Our data also suggest that levamisole, a potent immunostimulant drug, had no effect on the unresponsiveness of the lymphocytes to PHA stimulation."} {"id": "PMID:172951", "title": "Isolation of herpes simplex virus clones and drug resistant mutants in microcultures.", "content": "Suitable dilutions of herpes simplex virus (HSV) preparations inoculated into microcultures of confluent monolayers of human foreskin or Vero cells, in individual wells of plastic \"microplates\", induced viral cytopathic effects that resulted from the infection of the cultures by single virus particles. The clonal nature of the viral progeny in isolated wells was supported by visual control over the development of viral foci and by statistical analysis. The method has the advantage of speed and economy, while it also yields a large primary clonal virus stock. HSV clones resistant to phosphonoacetic acid (PAA) and 5-iodo-2'-deoxyuridine (IUdR) could be readily isolated by the described technique.", "contents": "Isolation of herpes simplex virus clones and drug resistant mutants in microcultures. Suitable dilutions of herpes simplex virus (HSV) preparations inoculated into microcultures of confluent monolayers of human foreskin or Vero cells, in individual wells of plastic \"microplates\", induced viral cytopathic effects that resulted from the infection of the cultures by single virus particles. The clonal nature of the viral progeny in isolated wells was supported by visual control over the development of viral foci and by statistical analysis. The method has the advantage of speed and economy, while it also yields a large primary clonal virus stock. HSV clones resistant to phosphonoacetic acid (PAA) and 5-iodo-2'-deoxyuridine (IUdR) could be readily isolated by the described technique."} {"id": "PMID:172952", "title": "[Neuroradiological study of traumatic cervical spine (author's transl)].", "content": "Only special neuroradiological procedures allow a clear demonstration or exclusion of a traumatic lesion involving or threatening the intraspinal structures. The myelographies are of particular interest. The functional sagittal pneumostratigraphy is the most informative technique, except for the visualization of an avulsion of the plexus. For better selecting the patients for a gas myelography, a scintigraphy of the spinal leptomeningeal bag is very helpful. But the neurological problem may be suspected on the standard X-ray picture. The lateral walls - articular apophyses and the arcus - are well defined. The vascular conditions of the nedk are best appreciated by an arch aortography. A selective study of the carotids and vertebral arteries in functional positions of the head and neck may then proceed.", "contents": "[Neuroradiological study of traumatic cervical spine (author's transl)]. Only special neuroradiological procedures allow a clear demonstration or exclusion of a traumatic lesion involving or threatening the intraspinal structures. The myelographies are of particular interest. The functional sagittal pneumostratigraphy is the most informative technique, except for the visualization of an avulsion of the plexus. For better selecting the patients for a gas myelography, a scintigraphy of the spinal leptomeningeal bag is very helpful. But the neurological problem may be suspected on the standard X-ray picture. The lateral walls - articular apophyses and the arcus - are well defined. The vascular conditions of the nedk are best appreciated by an arch aortography. A selective study of the carotids and vertebral arteries in functional positions of the head and neck may then proceed."} {"id": "PMID:172953", "title": "[Early histological findings of carcinoma of the breast (author's transl)].", "content": "Histologically the early histological findings of the carcinoma of the breast enclose lobular and intraductal carcinoma in situ, and atypical epithelial proliferation. Without mastectomy a considerable percentage of these cases will develop invasive carcinoma. In order to detect these early forms of carcinoma mammography should be carried out. Following this procedure a more precisely located histological examination can be performed. The treatment consists of simple mastectomy.", "contents": "[Early histological findings of carcinoma of the breast (author's transl)]. Histologically the early histological findings of the carcinoma of the breast enclose lobular and intraductal carcinoma in situ, and atypical epithelial proliferation. Without mastectomy a considerable percentage of these cases will develop invasive carcinoma. In order to detect these early forms of carcinoma mammography should be carried out. Following this procedure a more precisely located histological examination can be performed. The treatment consists of simple mastectomy."} {"id": "PMID:172954", "title": "Focal decreased skeletal uptake secondary to metastatic disease.", "content": "Two cases are reported in which bone imaging with 99mTc-labeled phosphate compounds revealed localized areas of decreased uptake corresponding to osteolytic metastases on bone radiographs. These \"cold\" bone lesions, although infrequent, should be considered to avoid false negative interpretations.", "contents": "Focal decreased skeletal uptake secondary to metastatic disease. Two cases are reported in which bone imaging with 99mTc-labeled phosphate compounds revealed localized areas of decreased uptake corresponding to osteolytic metastases on bone radiographs. These \"cold\" bone lesions, although infrequent, should be considered to avoid false negative interpretations."} {"id": "PMID:172955", "title": "Newer angiographic observations in cholangiocarcinoma.", "content": "Three new angiographic features of cholangiocarcinoma are bile duct dilatation, venous obstruction and arterio-arterial collaterals. Differentiation of the lucencies of dilated bile ducts (cylindrical in shape) from those due to metastases (spherical) is discussed. Because of its high reliability and the difficulties of operative diagnosis, angiography can play an important diagnostic role in patients with suspected cholangiocarcinoma.", "contents": "Newer angiographic observations in cholangiocarcinoma. Three new angiographic features of cholangiocarcinoma are bile duct dilatation, venous obstruction and arterio-arterial collaterals. Differentiation of the lucencies of dilated bile ducts (cylindrical in shape) from those due to metastases (spherical) is discussed. Because of its high reliability and the difficulties of operative diagnosis, angiography can play an important diagnostic role in patients with suspected cholangiocarcinoma."} {"id": "PMID:172980", "title": "Inhibition of prostaglandin E2-induced cyclic amp accumulation in the rat anterior pituitary by 11-deoxyprostaglandin E analogs (9-ketoprostynoic acids).", "content": "The effects of various 11-deoxyprostaglandin E analogs on the basal and prostaglandin E2 (PGE2)-induced cyclic AMP accumulation in the rat anterior pituitary were studied in vitro. 13-Hydroxy-9-oxoprost-14-ynoic acid at 5 X 10(-4)M but not 5 X 10(-5)M, decreased (45%) the induced accumulation and did not alter the basal accmulation; 15-hydroxy-9-oxoprost-13-ynoic acid at 5 X 10(-4)M caused less of a decrease (29%) in the induced and also did not alter the basal accumulation. (14Z)-13-Hydroxy-9-oxoprost-14-enoic acid at 5 X 10(-4)M did not alter the induced and caused a slight increase (5 fold) in the basal accumulation. 7-Oxa-13-prostynoic acid increased slightly the basal accumulation at 5 X 10(-5)M (2 fold) and 2.33 X 10(-4)M (6-fold) and did not antagonize the induced accumulation. Thus, the 9-ketoprostynoic acids are effective PGE2 antagonists in this system.", "contents": "Inhibition of prostaglandin E2-induced cyclic amp accumulation in the rat anterior pituitary by 11-deoxyprostaglandin E analogs (9-ketoprostynoic acids). The effects of various 11-deoxyprostaglandin E analogs on the basal and prostaglandin E2 (PGE2)-induced cyclic AMP accumulation in the rat anterior pituitary were studied in vitro. 13-Hydroxy-9-oxoprost-14-ynoic acid at 5 X 10(-4)M but not 5 X 10(-5)M, decreased (45%) the induced accumulation and did not alter the basal accmulation; 15-hydroxy-9-oxoprost-13-ynoic acid at 5 X 10(-4)M caused less of a decrease (29%) in the induced and also did not alter the basal accumulation. (14Z)-13-Hydroxy-9-oxoprost-14-enoic acid at 5 X 10(-4)M did not alter the induced and caused a slight increase (5 fold) in the basal accumulation. 7-Oxa-13-prostynoic acid increased slightly the basal accumulation at 5 X 10(-5)M (2 fold) and 2.33 X 10(-4)M (6-fold) and did not antagonize the induced accumulation. Thus, the 9-ketoprostynoic acids are effective PGE2 antagonists in this system."} {"id": "PMID:172981", "title": "ACTH-induced prostaglandin biosynthesis from 3H-arachidonic acid by adrenocortical cells.", "content": "Prostaglandins biosynthesized from 3H-arachidonic acid by trypsin-dispersed cat adrenocortical cells were isolated by silicic acid and thin layer chromatography. PGE, PGF, and a third component with mobility properties indistinguishable from either PGA or PGB were identified both in cortical cell homogenates and incubation medium. Concentrations of ACTH (125-250 muU) which stimulate steroidogenesis enhanced the conversion of labeled precursor to all three of these prostaglandins. These findings provide further evidence for the proposal that prostaglandins function as a critical link in ACTH-induced steroidogenesis.", "contents": "ACTH-induced prostaglandin biosynthesis from 3H-arachidonic acid by adrenocortical cells. Prostaglandins biosynthesized from 3H-arachidonic acid by trypsin-dispersed cat adrenocortical cells were isolated by silicic acid and thin layer chromatography. PGE, PGF, and a third component with mobility properties indistinguishable from either PGA or PGB were identified both in cortical cell homogenates and incubation medium. Concentrations of ACTH (125-250 muU) which stimulate steroidogenesis enhanced the conversion of labeled precursor to all three of these prostaglandins. These findings provide further evidence for the proposal that prostaglandins function as a critical link in ACTH-induced steroidogenesis."} {"id": "PMID:172982", "title": "Effects of indomethacin on intestinal secretion, prostaglandin E and cyclic AMP: evidence against a role for prostaglandins in cholera toxin-induced secretion.", "content": "The effects of indomethacin on intestine mucosal cAMP, intestinal fluid secretion, and mucosal and fluid PGE were studied in rabbits in vivo following challenge with cholera toxin. Indomethacin had no effect on cholera toxin-induced fluid secretion or cAMP accumulation. Inhibition of PGE synthesis was achieved by the administration of two but not one injection of indomethacin. These studies provide evidence against a role for PGE in mediating cholera toxin-induced secretion and point out the need to measure prostaglandin levels when using prostaglandin synthetase inhibitors in vivo.", "contents": "Effects of indomethacin on intestinal secretion, prostaglandin E and cyclic AMP: evidence against a role for prostaglandins in cholera toxin-induced secretion. The effects of indomethacin on intestine mucosal cAMP, intestinal fluid secretion, and mucosal and fluid PGE were studied in rabbits in vivo following challenge with cholera toxin. Indomethacin had no effect on cholera toxin-induced fluid secretion or cAMP accumulation. Inhibition of PGE synthesis was achieved by the administration of two but not one injection of indomethacin. These studies provide evidence against a role for PGE in mediating cholera toxin-induced secretion and point out the need to measure prostaglandin levels when using prostaglandin synthetase inhibitors in vivo."} {"id": "PMID:172983", "title": "The relationship between prostaglandin release and lung c-AMP levels during anaphylaxis in the guinea-pig.", "content": "A four-fold transient rise in c-AMP levels was seen when sensitized guinea-pig lungs were challenged with antigen in vitro. This rise in c-AMP also occurred in vivo and was shown to be due to release of Prostaglandin E2. This conclusion is supported by the finding that inhibitors of prostaglandin synthesis (Indomethacin and Poly phloretin phosphate) prevent the rise in c-AMP while neither ICI 74, 917, an inhibitor of histamine release, nor antihistamines had any effect on the c-AMP levels.", "contents": "The relationship between prostaglandin release and lung c-AMP levels during anaphylaxis in the guinea-pig. A four-fold transient rise in c-AMP levels was seen when sensitized guinea-pig lungs were challenged with antigen in vitro. This rise in c-AMP also occurred in vivo and was shown to be due to release of Prostaglandin E2. This conclusion is supported by the finding that inhibitors of prostaglandin synthesis (Indomethacin and Poly phloretin phosphate) prevent the rise in c-AMP while neither ICI 74, 917, an inhibitor of histamine release, nor antihistamines had any effect on the c-AMP levels."} {"id": "PMID:172988", "title": "On the role of mitochondria in the hereditary cardiomyopathy of the Syrian hamster.", "content": "Conventional polarographic techniques reveal no defect of oxidative phosphorylation in cardiomyopathic hamster heart mitochondria. However, in skeletal muscle of the same animals a defect is seen consistently with NAD+-linked substrates. This mitochondrial defect is caused by calcium accumulation and a consequent loss of NAD+ and magnesium. As shown by density gradient centrifugation, the defect resides in only a small fraction of all mitochondria. It is assumed that the same genetic defect in BIO 14.6 hamsters causes both skeletal muscle and heart lesions. Calcium levels in heart mitochondria are also significantly elevated in heart mitochondria. It is postulated that a calcium-associated defect similar to that in skeletal muscle mitochondria exists also in a very small fraction of the heart organelles and is responsible for the occurrence of focal necrosis.", "contents": "On the role of mitochondria in the hereditary cardiomyopathy of the Syrian hamster. Conventional polarographic techniques reveal no defect of oxidative phosphorylation in cardiomyopathic hamster heart mitochondria. However, in skeletal muscle of the same animals a defect is seen consistently with NAD+-linked substrates. This mitochondrial defect is caused by calcium accumulation and a consequent loss of NAD+ and magnesium. As shown by density gradient centrifugation, the defect resides in only a small fraction of all mitochondria. It is assumed that the same genetic defect in BIO 14.6 hamsters causes both skeletal muscle and heart lesions. Calcium levels in heart mitochondria are also significantly elevated in heart mitochondria. It is postulated that a calcium-associated defect similar to that in skeletal muscle mitochondria exists also in a very small fraction of the heart organelles and is responsible for the occurrence of focal necrosis."} {"id": "PMID:172989", "title": "Structural and functional characteristics of membrane fractions from cardiomyopathic and dystrophic muscle.", "content": "Subcellular fractions from ventricular muscle of the cardiomyopathic Syrian hamster and breast muscle from the dystrophic chicken were prepared by zonal centrifugation in sucrose gradients. This tenchnique permitted the analysis of a wide spectrum of subcellular particles prior to sedimentation, thus avoiding loss of activity through particle clumping. Substantial differences in the distribution of beta-glucuronidase and p-nitrophenyl-phosphatase in zonal fractions from myopathic and control tissues provided evidence for contamination of fractions containing fragmented sarcoplasmic reticulum by lysosomes. This contamination may contribute signifantly to the altered lipid composition and Ca2+ transport function of the myopathic preparations.", "contents": "Structural and functional characteristics of membrane fractions from cardiomyopathic and dystrophic muscle. Subcellular fractions from ventricular muscle of the cardiomyopathic Syrian hamster and breast muscle from the dystrophic chicken were prepared by zonal centrifugation in sucrose gradients. This tenchnique permitted the analysis of a wide spectrum of subcellular particles prior to sedimentation, thus avoiding loss of activity through particle clumping. Substantial differences in the distribution of beta-glucuronidase and p-nitrophenyl-phosphatase in zonal fractions from myopathic and control tissues provided evidence for contamination of fractions containing fragmented sarcoplasmic reticulum by lysosomes. This contamination may contribute signifantly to the altered lipid composition and Ca2+ transport function of the myopathic preparations."} {"id": "PMID:172990", "title": "Ultrastructural myocardial changes produced by viruses.", "content": "Some of the ultrastructural pathological alterations in the myocardium produced by viral infections with members of the picornavirus group are described. These alterations varied from mild to severe, with necrosis. In animals infected with Coxsackie B1 virus and EMC virus, readily identifiable viral crystals were frequently found in association with the myocardial lesions by means of electron microscopy. The electron microscope made it possible to study vary early myocardial changes which were not detected with the light microscope. Although the ultrastructural myocardial changes in rheumatic fever have received little attention, the light and electron microscopic findings in the myocardium and valves of the viral-infected animals described here closely resemble those described in man in association with so-called rheumatic heart disease. The type of investigations presented forms a good model for the study of the natural history of ultrastructural pathology produced in all parts of the heart by viruses.", "contents": "Ultrastructural myocardial changes produced by viruses. Some of the ultrastructural pathological alterations in the myocardium produced by viral infections with members of the picornavirus group are described. These alterations varied from mild to severe, with necrosis. In animals infected with Coxsackie B1 virus and EMC virus, readily identifiable viral crystals were frequently found in association with the myocardial lesions by means of electron microscopy. The electron microscope made it possible to study vary early myocardial changes which were not detected with the light microscope. Although the ultrastructural myocardial changes in rheumatic fever have received little attention, the light and electron microscopic findings in the myocardium and valves of the viral-infected animals described here closely resemble those described in man in association with so-called rheumatic heart disease. The type of investigations presented forms a good model for the study of the natural history of ultrastructural pathology produced in all parts of the heart by viruses."} {"id": "PMID:172991", "title": "Virus-induced damage of the myocardial cell.", "content": "A total of 330 male 3-week-old mice of the N.M.R.I./Han. strain were infected with the M-variant of the EMC (encephalomyocarditis) virus by subcutaneous inoculation of 0.25 ml of the virus suspension diluted 1:500. Animals were killed at 4- or 6-hour intervals, respectively, and groups of 2 to 8 hearts were taken for virological, morphological, and biochemical studies. Before the 8th hour after the inoculation, no virus and no pathological cell changes could be detected in the hearts; it is assumed, therefore, that there first takes place an extracardiac virus cultiplication. The virus content in the hearts increases from the 12th to the 30th ahour and subsequently maintains that level. Also from the 12th to the 30th hour, electron microscopy reveals increasing damage of the myocardial cells, the course of which is described. In most instances following virus-induced damage of the myocardial cells, the onset of alterations of the blood and lymph capillaries and damage to the interstitial cells were observed...", "contents": "Virus-induced damage of the myocardial cell. A total of 330 male 3-week-old mice of the N.M.R.I./Han. strain were infected with the M-variant of the EMC (encephalomyocarditis) virus by subcutaneous inoculation of 0.25 ml of the virus suspension diluted 1:500. Animals were killed at 4- or 6-hour intervals, respectively, and groups of 2 to 8 hearts were taken for virological, morphological, and biochemical studies. Before the 8th hour after the inoculation, no virus and no pathological cell changes could be detected in the hearts; it is assumed, therefore, that there first takes place an extracardiac virus cultiplication. The virus content in the hearts increases from the 12th to the 30th ahour and subsequently maintains that level. Also from the 12th to the 30th hour, electron microscopy reveals increasing damage of the myocardial cells, the course of which is described. In most instances following virus-induced damage of the myocardial cells, the onset of alterations of the blood and lymph capillaries and damage to the interstitial cells were observed..."} {"id": "PMID:172996", "title": "Spin labeled acetylcholine analogs: studies of cholinergic receptor.", "content": "Some spin-labeled acetylcholine analogs, in which the number of methylene groups between the quaternary nitrogen and the ether oxygen ranged between 1-5, were synthesized to study drug interacitons with acetylcholine receptors. None of the compounds tested, with the exception of the one that contained 2 methylene groups (SL-2) had any cholinergic activity. SL-2 was not capable of producing any nicotinic cholinomimetic activity. On the other hand it proved to have a very weak nicotinic cholinolytic activity on the receptors of the frog satorius muscle. This compound exhibited strong antagonism against muscarinic receptors of the isolated frog heart. The muscarinic cholinolytic action of the spin-label ACh analog is discussed in terms of the molecular perturbation theory of drug action.", "contents": "Spin labeled acetylcholine analogs: studies of cholinergic receptor. Some spin-labeled acetylcholine analogs, in which the number of methylene groups between the quaternary nitrogen and the ether oxygen ranged between 1-5, were synthesized to study drug interacitons with acetylcholine receptors. None of the compounds tested, with the exception of the one that contained 2 methylene groups (SL-2) had any cholinergic activity. SL-2 was not capable of producing any nicotinic cholinomimetic activity. On the other hand it proved to have a very weak nicotinic cholinolytic activity on the receptors of the frog satorius muscle. This compound exhibited strong antagonism against muscarinic receptors of the isolated frog heart. The muscarinic cholinolytic action of the spin-label ACh analog is discussed in terms of the molecular perturbation theory of drug action."} {"id": "PMID:172997", "title": "The growth characteristics of the metastatic Wistar/Furth Wilms' tumor model.", "content": "Growth characteristics, metastatic spread, and survival times were evaluated in a transplantable Wistar/Furth rat Wilms' tumor model. Tumor suspensions of various tumor cell dosages were injected in an attempt to find the optimum level of tumor take. Lung metastases were frequent following tumor injection by all routes. However, tumor spread to the lungs was the least frequent following subcutaneous (SC) injection of the tumor. Survival time for the intramuscular (IM) group was statistically longer at all tumor dose levels. For the 1 X 10(5) tumor dosage, survival time ranged from a mean of 27 days for the intrarenal (IR) group to a mean 42 days for the IM group. For the 1 X 10(4) dosage, survival time ranged from a mean of 37 days for the intraperitoneal (IP) group to a mean of 51 days for the IM group. It is concluded that this animal tumor closely resembles the human Wilms' tumor, and that the point at which the transplanted tumor fails to be successfully transplanted is below the dosage level of 1 X 10(3) tumor cells.", "contents": "The growth characteristics of the metastatic Wistar/Furth Wilms' tumor model. Growth characteristics, metastatic spread, and survival times were evaluated in a transplantable Wistar/Furth rat Wilms' tumor model. Tumor suspensions of various tumor cell dosages were injected in an attempt to find the optimum level of tumor take. Lung metastases were frequent following tumor injection by all routes. However, tumor spread to the lungs was the least frequent following subcutaneous (SC) injection of the tumor. Survival time for the intramuscular (IM) group was statistically longer at all tumor dose levels. For the 1 X 10(5) tumor dosage, survival time ranged from a mean of 27 days for the intrarenal (IR) group to a mean 42 days for the IM group. For the 1 X 10(4) dosage, survival time ranged from a mean of 37 days for the intraperitoneal (IP) group to a mean of 51 days for the IM group. It is concluded that this animal tumor closely resembles the human Wilms' tumor, and that the point at which the transplanted tumor fails to be successfully transplanted is below the dosage level of 1 X 10(3) tumor cells."} {"id": "PMID:172998", "title": "Serum and host liver activities of glycosidases and sialyltransferases in animals bearing transplantable tumors.", "content": "Rats bearing Reuber H-35 or Novikoff hepatomas and mice bearing L1210 or L5178Y murine leukemias exhibited elevated serum levels of fetuin : N-acetylneuraminic acid transferase (EC 2.4.99.1) activity. The serum transferase activity could be correlated with the growth rate of the tumor; in animals bearing the more rapidly growing Novikoff hepatoma, activity was higher than in animals bearing the Reuber H-35 hepatoma. Higher transferase levels were also found in L1210 leukemic mice than in mice with the slightly slower growing L5178Y leukemia. Serum from rats bearing Reuber H-35 hepatoma and mice bearing L1210 murine leukemia had elevated levels of alpha- and beta-glucosidase (EC 3.2.1.20 and EC 3.2.1.21), alpha- and beta-galactosidase (EC 3.2.1.22 and (3.2.1.23), beta mannosidase (EC 3.2.1.25), alpha- and beta-fucosidase (EC 3.2.1.- and EC 3.2.1.38), beta-N-acetylglucosaminidase (EC 3.2.1.30) and acid phosphatase (EC 3.1.3.2); alpha-mannosidase (EC 3.2.1.24), beta-N-acetylgalactosaminidase (EC 3.2.2.-) and beta-xylosidase (EC 3.2.1.37) were not elevated. In animals bearing Reuber H-35 hepatoma, host liver levels of glycosidases, beta-glucuronidase (EC 3.2.1.31) and acid phosphatase were elevated over both the control and the hepatoma values. The data are interpreted to mean that the tumors or various host tissues release large quantities of enzymes into the serum and that enzyme levels in host organs may also be affected by the tumor.", "contents": "Serum and host liver activities of glycosidases and sialyltransferases in animals bearing transplantable tumors. Rats bearing Reuber H-35 or Novikoff hepatomas and mice bearing L1210 or L5178Y murine leukemias exhibited elevated serum levels of fetuin : N-acetylneuraminic acid transferase (EC 2.4.99.1) activity. The serum transferase activity could be correlated with the growth rate of the tumor; in animals bearing the more rapidly growing Novikoff hepatoma, activity was higher than in animals bearing the Reuber H-35 hepatoma. Higher transferase levels were also found in L1210 leukemic mice than in mice with the slightly slower growing L5178Y leukemia. Serum from rats bearing Reuber H-35 hepatoma and mice bearing L1210 murine leukemia had elevated levels of alpha- and beta-glucosidase (EC 3.2.1.20 and EC 3.2.1.21), alpha- and beta-galactosidase (EC 3.2.1.22 and (3.2.1.23), beta mannosidase (EC 3.2.1.25), alpha- and beta-fucosidase (EC 3.2.1.- and EC 3.2.1.38), beta-N-acetylglucosaminidase (EC 3.2.1.30) and acid phosphatase (EC 3.1.3.2); alpha-mannosidase (EC 3.2.1.24), beta-N-acetylgalactosaminidase (EC 3.2.2.-) and beta-xylosidase (EC 3.2.1.37) were not elevated. In animals bearing Reuber H-35 hepatoma, host liver levels of glycosidases, beta-glucuronidase (EC 3.2.1.31) and acid phosphatase were elevated over both the control and the hepatoma values. The data are interpreted to mean that the tumors or various host tissues release large quantities of enzymes into the serum and that enzyme levels in host organs may also be affected by the tumor."} {"id": "PMID:172999", "title": "Effect of hydroxycobalamin on the inhibition of cytochrome c oxidase by cyanide. I - In intact mitochondria.", "content": "The effects of hydroxycobalamin on inhibition of cytochrome c oxidase by cyanida in isolated intact mitochondria were studied. No effect of hydroxycobalamin (HCo) and cyanocobalamin (CNCo) was observed on normal mitochondria. When mitochondria inhibited by cyanida were treated with HCo the respiration with ADP, the respiration after ADP and respiratory coefficient (RC) were increased. No effect was observed with CNCo. Difference spectra of the effect of HCo on the inhibition of cytochrome c oxidase by cyanida and azide in isolated intact mitochondria were recorded using a split beam spectrophotometer. The results presented herein suggest that HCo reverses the cyanide inhibition because part of cytochrome a3 is free from cyanide as a consequence of dissociation of the complex, resulting in CNCo formation. If this reaction continues to occur together with a probable by pass between cytochrome a and oxygen throught the HCo (which was not transformed in CNCo), oxygen consumption and most of the respiratory chain will be maitened in the active state.", "contents": "Effect of hydroxycobalamin on the inhibition of cytochrome c oxidase by cyanide. I - In intact mitochondria. The effects of hydroxycobalamin on inhibition of cytochrome c oxidase by cyanida in isolated intact mitochondria were studied. No effect of hydroxycobalamin (HCo) and cyanocobalamin (CNCo) was observed on normal mitochondria. When mitochondria inhibited by cyanida were treated with HCo the respiration with ADP, the respiration after ADP and respiratory coefficient (RC) were increased. No effect was observed with CNCo. Difference spectra of the effect of HCo on the inhibition of cytochrome c oxidase by cyanida and azide in isolated intact mitochondria were recorded using a split beam spectrophotometer. The results presented herein suggest that HCo reverses the cyanide inhibition because part of cytochrome a3 is free from cyanide as a consequence of dissociation of the complex, resulting in CNCo formation. If this reaction continues to occur together with a probable by pass between cytochrome a and oxygen throught the HCo (which was not transformed in CNCo), oxygen consumption and most of the respiratory chain will be maitened in the active state."} {"id": "PMID:173000", "title": "[Exocrine pancreatic function and calcium balance. Experimental studies of the effect of parathyroid hormone, vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin and thyrocalcitonin (author's transl)].", "content": "The effect of the acute elevation of extracellular calcium concentration, of vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin, parathyroid hormone and of thyrocalcitonin on the exocrine function of the perfused cat pancreas was studied. Elevation of the perfusate calcium concentration resulted in an initial increase in the enzyme and, occasionally, calcium concentration of the pancreatic juice, the flow rate and the secretion of magnesium and chloride were not very much altered. The application of vitamin D3 and 25-hydroxycholecalciferol elevated the stimulated (by acetylcholine or cholecystokinin-pancreocymin) protein and enzyme output (lipase, alpha-amylase). Parathyroid hormone and, especially, thyreocalcitonin inhibited the stimulated protein and enzyme secretion, volume and rate of the electrolyte secretion were not changed. In states of calcium excess the stimulated protein output was decreased by both vitamin D3 and parathyroid hormone.", "contents": "[Exocrine pancreatic function and calcium balance. Experimental studies of the effect of parathyroid hormone, vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin and thyrocalcitonin (author's transl)]. The effect of the acute elevation of extracellular calcium concentration, of vitamin D3, 25-hydroxycholecalciferol, dihydrotachysterin, parathyroid hormone and of thyrocalcitonin on the exocrine function of the perfused cat pancreas was studied. Elevation of the perfusate calcium concentration resulted in an initial increase in the enzyme and, occasionally, calcium concentration of the pancreatic juice, the flow rate and the secretion of magnesium and chloride were not very much altered. The application of vitamin D3 and 25-hydroxycholecalciferol elevated the stimulated (by acetylcholine or cholecystokinin-pancreocymin) protein and enzyme output (lipase, alpha-amylase). Parathyroid hormone and, especially, thyreocalcitonin inhibited the stimulated protein and enzyme secretion, volume and rate of the electrolyte secretion were not changed. In states of calcium excess the stimulated protein output was decreased by both vitamin D3 and parathyroid hormone."} {"id": "PMID:173001", "title": "Occupational type test for the etiological diagnosis of asthma due to toluene di-isocyanate.", "content": "An occupational type exposure-test to toluene di-isocyanate (TDI) for the diagnosis of specific respiratory sensitization is proposed. The subjects were tested by exposure to a two-pot polyurethane varnish with and without TDI activator, using a paint-spraying system under standard and controlled conditions, so as not to exceed the threshold limit value of TDI. Forced expiratory volume per second and specific airway resistance (plethysmographic method) were measured before each exposure and during the following 24 h. 47 subjects with clinical symptoms of asthma were examined during their hospital care. For the purpose of this study they were divided into two groups: 42 workers exposed to TDI and 5 not exposed. The preliminary control test, using polyurethane varnish without TDI activator, was always negative and no significant changes in ventilatory parameters were recorded. The spray-painting test, with the same varnish and TDI activator, gave positive responses in 35 out of the 42 exposed workers and negative findings in the group not exposed. This method permits to formulate an accurate diagnosis of TDI respiratory sensitization in the majority of cases (83%). Immediate asthmatic reactions were frequently observed in the exposed subjects with high acetylcholine reactivity. Ten subjects showed a late bronchial reaction (3 h or more after TDI exposure).", "contents": "Occupational type test for the etiological diagnosis of asthma due to toluene di-isocyanate. An occupational type exposure-test to toluene di-isocyanate (TDI) for the diagnosis of specific respiratory sensitization is proposed. The subjects were tested by exposure to a two-pot polyurethane varnish with and without TDI activator, using a paint-spraying system under standard and controlled conditions, so as not to exceed the threshold limit value of TDI. Forced expiratory volume per second and specific airway resistance (plethysmographic method) were measured before each exposure and during the following 24 h. 47 subjects with clinical symptoms of asthma were examined during their hospital care. For the purpose of this study they were divided into two groups: 42 workers exposed to TDI and 5 not exposed. The preliminary control test, using polyurethane varnish without TDI activator, was always negative and no significant changes in ventilatory parameters were recorded. The spray-painting test, with the same varnish and TDI activator, gave positive responses in 35 out of the 42 exposed workers and negative findings in the group not exposed. This method permits to formulate an accurate diagnosis of TDI respiratory sensitization in the majority of cases (83%). Immediate asthmatic reactions were frequently observed in the exposed subjects with high acetylcholine reactivity. Ten subjects showed a late bronchial reaction (3 h or more after TDI exposure)."} {"id": "PMID:173002", "title": "Can VA/Q distributions in the lung be recovered from inert gas retention data?", "content": "It has been suggested that the true distribution of ventilation-perfusion ratios can be determined from measurements made during the excretion of six different inert gases. This report shows that a number of considerably different distribution patterns will yield the same retention data, even in the absence of analytical error. Therefore, although analysis of inert gas retention data will allow one to arrive at a VA/Q distribution, it will not necessarily be the correct distribution.", "contents": "Can VA/Q distributions in the lung be recovered from inert gas retention data? It has been suggested that the true distribution of ventilation-perfusion ratios can be determined from measurements made during the excretion of six different inert gases. This report shows that a number of considerably different distribution patterns will yield the same retention data, even in the absence of analytical error. Therefore, although analysis of inert gas retention data will allow one to arrive at a VA/Q distribution, it will not necessarily be the correct distribution."} {"id": "PMID:173004", "title": "[Heterochronia of nerve fibers in man. Diagnostic value: initial results].", "content": "A classical physiological observation not usually apparent with methods used for detecting nerve potential in man, heterochronia of the nerve fibres is often found in extraordinary circumstances with considerably higher than normal frequence : mainly in muscular disorders, in particular myotonic dystrophy ; more incidentally in disorders of muscle tone. The authors draw attention to certain sources of error which could lead to wrong diagnosis of heterochronia and emphasize that these are only the initial results of research which needs to be pursued further.", "contents": "[Heterochronia of nerve fibers in man. Diagnostic value: initial results]. A classical physiological observation not usually apparent with methods used for detecting nerve potential in man, heterochronia of the nerve fibres is often found in extraordinary circumstances with considerably higher than normal frequence : mainly in muscular disorders, in particular myotonic dystrophy ; more incidentally in disorders of muscle tone. The authors draw attention to certain sources of error which could lead to wrong diagnosis of heterochronia and emphasize that these are only the initial results of research which needs to be pursued further."} {"id": "PMID:173005", "title": "[Study of afferent conduction in the external saphenous nerve using the method of evoked cerebral potentials].", "content": "By the comparison of nerve action potentials and cerebral potentials evoked by the same electrical stimulus the propagation of the somaesthetic impulse to the cerebral cortex can be evaluated. This technique was applied to the fibres of the sural nerve in normal subjects and in patients presenting various lesions of the peripheral and central nervous system. Evoked cerebral potential afforded valuable data when it was not possible to record the nerve action potentials or when the lesion involved the central segment of the afferent pathway.", "contents": "[Study of afferent conduction in the external saphenous nerve using the method of evoked cerebral potentials]. By the comparison of nerve action potentials and cerebral potentials evoked by the same electrical stimulus the propagation of the somaesthetic impulse to the cerebral cortex can be evaluated. This technique was applied to the fibres of the sural nerve in normal subjects and in patients presenting various lesions of the peripheral and central nervous system. Evoked cerebral potential afforded valuable data when it was not possible to record the nerve action potentials or when the lesion involved the central segment of the afferent pathway."} {"id": "PMID:173006", "title": "[Physiopathological and neuropathological study of a cerebral decortication syndrome].", "content": "Detailed observation of a case of laminar necrosis of almost the whole of the cerebral cortex has led to several deductions concerning the physiology of the cortex in man. It suggests that the cortex has a limited influence on sleep, interfering particularly in the electro-encephalographic translation of slow sleep and, curiously, in the organisation of sleep, paradoxical sleep is hardly affected at all. It confirms the importance of the human cortex in the acquisition of elementary skills and describes a new oculomotor pattern in a decorticate man.", "contents": "[Physiopathological and neuropathological study of a cerebral decortication syndrome]. Detailed observation of a case of laminar necrosis of almost the whole of the cerebral cortex has led to several deductions concerning the physiology of the cortex in man. It suggests that the cortex has a limited influence on sleep, interfering particularly in the electro-encephalographic translation of slow sleep and, curiously, in the organisation of sleep, paradoxical sleep is hardly affected at all. It confirms the importance of the human cortex in the acquisition of elementary skills and describes a new oculomotor pattern in a decorticate man."} {"id": "PMID:173010", "title": "Virologic studies in rheumatoid arthritis.", "content": "Comparison of virus antibody titers in JRA and matched controls failed to implicate rubella, measles, parainfluenza type 1 or Epstein-Barr viruses. Neither RNA viruses or mycoplasma were detected in rheumatoid synovial cell cultures by 3H-uridine incorporation. Mycoplasma were not isolated from rheumatoid synovial membranes or cell cultures using the large specimen-broth culture procedure. The balance of available evidence, including our own, suggests that mycoplasma are not involved in RA. Viruses, however, are better candidates, in spite of similar generally negative studies to date, because methods for detecting known latent infection in animals and in vitro are still in their infancy. Those that are known have not yet been comprehensively applied to RA. Thus, supported by indirect evidence from animal models and human diseases like polyarteritis, the hypothesis that viruses are involved in the pathogenesis of RA remains attractive, although direct evidence is still lacking.", "contents": "Virologic studies in rheumatoid arthritis. Comparison of virus antibody titers in JRA and matched controls failed to implicate rubella, measles, parainfluenza type 1 or Epstein-Barr viruses. Neither RNA viruses or mycoplasma were detected in rheumatoid synovial cell cultures by 3H-uridine incorporation. Mycoplasma were not isolated from rheumatoid synovial membranes or cell cultures using the large specimen-broth culture procedure. The balance of available evidence, including our own, suggests that mycoplasma are not involved in RA. Viruses, however, are better candidates, in spite of similar generally negative studies to date, because methods for detecting known latent infection in animals and in vitro are still in their infancy. Those that are known have not yet been comprehensively applied to RA. Thus, supported by indirect evidence from animal models and human diseases like polyarteritis, the hypothesis that viruses are involved in the pathogenesis of RA remains attractive, although direct evidence is still lacking."} {"id": "PMID:173009", "title": "[Serological studies of the role of the respiratory syncytial virus in acute respiratory diseases in children].", "content": "The presence of the syncytial respiratory virus was determined by CF in 281 children admitted with acute respiratory diseases between 15 Sept. 1971 and 30 Dec. 1973, using the Long antigen prepared in the \"St. Nicolau\" Institute of Virology, Bucharest. In 38 children (13.5%) a serologic diagnosis of infection with the syncytial virus was established; in the other cases of respiratory infection of different etiology, antibodies to the syncytial virus were found in low but constant titers in both serum samples. The presence of these antibodies in a high proportion of the children points to the wide circulation of the syncytial virus in the infantile population, with all its clinico-epidemiologic implications.", "contents": "[Serological studies of the role of the respiratory syncytial virus in acute respiratory diseases in children]. The presence of the syncytial respiratory virus was determined by CF in 281 children admitted with acute respiratory diseases between 15 Sept. 1971 and 30 Dec. 1973, using the Long antigen prepared in the \"St. Nicolau\" Institute of Virology, Bucharest. In 38 children (13.5%) a serologic diagnosis of infection with the syncytial virus was established; in the other cases of respiratory infection of different etiology, antibodies to the syncytial virus were found in low but constant titers in both serum samples. The presence of these antibodies in a high proportion of the children points to the wide circulation of the syncytial virus in the infantile population, with all its clinico-epidemiologic implications."} {"id": "PMID:173013", "title": "Effects of chronic ethanol abuse on structure and enzyme activities of skeletal muscle in man.", "content": "Biopsies from vastus lateralis muscle of male patients suffering from chronic ethanol abuse were studied with regard to histochemical reactions of ATPase and NADH-diaphorase; enzymatic activities of triosephosphate dehydrogenase (TPD), lactate dehydrogenase (LD), and cytochrome c oxidase (cytox); content of ATP, creatine phosphate, and glycogen; and volume fractions of fat, mitochondria, and fibrillar and extrafibrillar space. The results were compared with those from controls without known abuse of ethanol. The relative numbers of fibers were the same in two groups, but the size of the fast-twitch-glycolytic (white) fibers was diminished in the alcoholic group. The activities of TPD and LD were diminished in skeletal muscle of the alcoholics. This is most probably caused by the reduced amount of fast-twitch-glycolytic tissue, as there was a good correlation between this amount and the activity of the two enzymes. The activity of cytox was slightly lower in muscle of the alcoholics than in that of the controls. The volume fraction of mitochondria was lower in the alcoholic group than in the control group. Volume fractions of fat and fibrillar and extrafibrillar space were equal in the two groups. No significant differences were found in the amount of glycogen and ATP in the muscle of the two groups. However, the content of creatine phosphate is higher in the alcoholic group than in the control group.", "contents": "Effects of chronic ethanol abuse on structure and enzyme activities of skeletal muscle in man. Biopsies from vastus lateralis muscle of male patients suffering from chronic ethanol abuse were studied with regard to histochemical reactions of ATPase and NADH-diaphorase; enzymatic activities of triosephosphate dehydrogenase (TPD), lactate dehydrogenase (LD), and cytochrome c oxidase (cytox); content of ATP, creatine phosphate, and glycogen; and volume fractions of fat, mitochondria, and fibrillar and extrafibrillar space. The results were compared with those from controls without known abuse of ethanol. The relative numbers of fibers were the same in two groups, but the size of the fast-twitch-glycolytic (white) fibers was diminished in the alcoholic group. The activities of TPD and LD were diminished in skeletal muscle of the alcoholics. This is most probably caused by the reduced amount of fast-twitch-glycolytic tissue, as there was a good correlation between this amount and the activity of the two enzymes. The activity of cytox was slightly lower in muscle of the alcoholics than in that of the controls. The volume fraction of mitochondria was lower in the alcoholic group than in the control group. Volume fractions of fat and fibrillar and extrafibrillar space were equal in the two groups. No significant differences were found in the amount of glycogen and ATP in the muscle of the two groups. However, the content of creatine phosphate is higher in the alcoholic group than in the control group."} {"id": "PMID:173015", "title": "Effect of treatment with a bile-sequestering agent (Secholex) on intestinal absorption, duodenal bile acids, and plasma lipids.", "content": "Four female and five male patients (mean age 26 years) with hyperlipoproteinaemia type II A were treated with an anion exchange gel (Secholex) 9 g/day for 3 months and 15 g/day for 9 months. After these 12 months clofibrate 1.5 g/day was added to the therapy in 6 patients, whereas 2 patients continued with the resin alone for another 6 months, and one was withdrawn from the trial because of pregnancy. During the first year plasma cholesterol decreased averagely 18% from a mean pretreatment value of 461 mg/100 ml. Dosis of 9 g/day seemed to be as efficient as 15 g/day. When clofibrate was added, a further decrease of plasma cholesterol by 6% was observed, and the levels of triglycerides were reduced. Significantly increased concentrations of bile acids and a rise in the glycine/taurine ratio in duodenal aspirate were caused by the resin. On combined treatment the concentration of bile acids decreased to the pretreatment values, whereas the glycine/taurine ratio remained unchanged. During the trial slight transient changes in serum folic acid, fasting insulin, calcium, alkaline phosphatases, and vitamin B 12-absorption occurred. No changes in serum vitamin A, vitamin-K-dependent clotting factors, serum gastrin, gastric acid output, the absorption of glucose and iron, and faecal excretion of fat were observed. Serum insulin 30 and 60 minutes after an oral glucose loading decreased in the patients on combined treatment, whereas the insulin response remained normal in patients taking Secholex alone. Liver function tests and creatinine were unchanged during the trial. Apart from transient abdominal discomfort in two patients, no side-effects were discovered. The patients found the gel palatable.", "contents": "Effect of treatment with a bile-sequestering agent (Secholex) on intestinal absorption, duodenal bile acids, and plasma lipids. Four female and five male patients (mean age 26 years) with hyperlipoproteinaemia type II A were treated with an anion exchange gel (Secholex) 9 g/day for 3 months and 15 g/day for 9 months. After these 12 months clofibrate 1.5 g/day was added to the therapy in 6 patients, whereas 2 patients continued with the resin alone for another 6 months, and one was withdrawn from the trial because of pregnancy. During the first year plasma cholesterol decreased averagely 18% from a mean pretreatment value of 461 mg/100 ml. Dosis of 9 g/day seemed to be as efficient as 15 g/day. When clofibrate was added, a further decrease of plasma cholesterol by 6% was observed, and the levels of triglycerides were reduced. Significantly increased concentrations of bile acids and a rise in the glycine/taurine ratio in duodenal aspirate were caused by the resin. On combined treatment the concentration of bile acids decreased to the pretreatment values, whereas the glycine/taurine ratio remained unchanged. During the trial slight transient changes in serum folic acid, fasting insulin, calcium, alkaline phosphatases, and vitamin B 12-absorption occurred. No changes in serum vitamin A, vitamin-K-dependent clotting factors, serum gastrin, gastric acid output, the absorption of glucose and iron, and faecal excretion of fat were observed. Serum insulin 30 and 60 minutes after an oral glucose loading decreased in the patients on combined treatment, whereas the insulin response remained normal in patients taking Secholex alone. Liver function tests and creatinine were unchanged during the trial. Apart from transient abdominal discomfort in two patients, no side-effects were discovered. The patients found the gel palatable."} {"id": "PMID:173016", "title": "Cell production and cell function in human cyclic neutropenia.", "content": "In vitro studies have been done on haematopoietic cells from a patient with cyclic neutropenia characterized by severe depression of blood neutrophil levels every 21 days. Serial blood counts reveal periodic fluctuations in neutrophils, monocytes and reticulocytes. Agar culture of marrow cells shows normal concentration of colony forming cells. The percentage of colony forming cells in S phase is highly increased during profound neutropenia and normal during the recovery phase relating the granulocyte production to the peripheral neutrophil level. Studies of ingestion rate, bactericidal activity, lactate production and glucose oxidation during phagocytosis in isolated granulocytes show normal results. Also the ingestion rate in isolated monocytes is normal. Serial karyotype analyses of marrow cells during the neutrophil cycle display a normal pattern. Serum myeloperoxidase levels vary inversely with the peripheral neutrophil count indicating increased granulopoietic activity during profound neutropenia, which might be associated with non effective granulopoiesis during profound neutropenia, leading to a lack of granulocyte reserves in the marrow.", "contents": "Cell production and cell function in human cyclic neutropenia. In vitro studies have been done on haematopoietic cells from a patient with cyclic neutropenia characterized by severe depression of blood neutrophil levels every 21 days. Serial blood counts reveal periodic fluctuations in neutrophils, monocytes and reticulocytes. Agar culture of marrow cells shows normal concentration of colony forming cells. The percentage of colony forming cells in S phase is highly increased during profound neutropenia and normal during the recovery phase relating the granulocyte production to the peripheral neutrophil level. Studies of ingestion rate, bactericidal activity, lactate production and glucose oxidation during phagocytosis in isolated granulocytes show normal results. Also the ingestion rate in isolated monocytes is normal. Serial karyotype analyses of marrow cells during the neutrophil cycle display a normal pattern. Serum myeloperoxidase levels vary inversely with the peripheral neutrophil count indicating increased granulopoietic activity during profound neutropenia, which might be associated with non effective granulopoiesis during profound neutropenia, leading to a lack of granulocyte reserves in the marrow."} {"id": "PMID:173017", "title": "Stimulation of normal lymphocytes with autologous lymphoid cell lines: properties of derived killer cells.", "content": "Lymphocytes from normal adults, with or without serological signs of previous Epstein-Barr virus (EBV) infection, could be stimulated to proliferate and produce killer cells by incubation with autologous EBV-genome-positive lymphoid cell lines (LCLs). The stimulated cells were most probably of T-cell origin, although at the peak of stimulation many of them lacked the sheep erythrocyte marker. Direct effector-target cell contact was necessary for lysis to occur. The cytotoxicity of autologously stimulated (AS) lymphocytes was not restricted to EBV-genome-positive LCLs, nor to cell lines of hematopoietic origin. It was equally broad if cells carrying complement receptor had been removed before stimulation. Fresh lymphocytes, blasts induced by phytohemagglutinin or concanavalin A, and Burkitt's lymphoma biopsy cells were resistant or considerably less sensitive. Mouse cells--even cell lines--were resistant. The sensitivity of target cells to lysis correlated positively with their capacity to block AS lymphocyte lysis of autologous LCLs in competition experiments. The cytotoxicity of AS lymphocytes was blocked by EBV-genome-positive and -negative cell lines, whereas the EBV-related cytotoxicity of T cells from acute cases of infectious mononucleosis was blocked by EBV-genome-positive LCL only.", "contents": "Stimulation of normal lymphocytes with autologous lymphoid cell lines: properties of derived killer cells. Lymphocytes from normal adults, with or without serological signs of previous Epstein-Barr virus (EBV) infection, could be stimulated to proliferate and produce killer cells by incubation with autologous EBV-genome-positive lymphoid cell lines (LCLs). The stimulated cells were most probably of T-cell origin, although at the peak of stimulation many of them lacked the sheep erythrocyte marker. Direct effector-target cell contact was necessary for lysis to occur. The cytotoxicity of autologously stimulated (AS) lymphocytes was not restricted to EBV-genome-positive LCLs, nor to cell lines of hematopoietic origin. It was equally broad if cells carrying complement receptor had been removed before stimulation. Fresh lymphocytes, blasts induced by phytohemagglutinin or concanavalin A, and Burkitt's lymphoma biopsy cells were resistant or considerably less sensitive. Mouse cells--even cell lines--were resistant. The sensitivity of target cells to lysis correlated positively with their capacity to block AS lymphocyte lysis of autologous LCLs in competition experiments. The cytotoxicity of AS lymphocytes was blocked by EBV-genome-positive and -negative cell lines, whereas the EBV-related cytotoxicity of T cells from acute cases of infectious mononucleosis was blocked by EBV-genome-positive LCL only."} {"id": "PMID:173018", "title": "Circadian periodicity a neurospora: alteration by inhibitors of cyclic AMP phosphodiesterase.", "content": "Three methyl xanthine inhibitors of adenosine 3',5'-monophosphate phosphodiesterase-theophylline, aminophyline, and caffeine-lengthen the period of the circadian conidiation rhythm of Neurospora. The effect are seen in wild-type strains and in three mutant strains with genetically altered period lengths. These results suggest the possible involvement of adenosine 3', 5'-monophosphate in the control of circadian rhythmicity.", "contents": "Circadian periodicity a neurospora: alteration by inhibitors of cyclic AMP phosphodiesterase. Three methyl xanthine inhibitors of adenosine 3',5'-monophosphate phosphodiesterase-theophylline, aminophyline, and caffeine-lengthen the period of the circadian conidiation rhythm of Neurospora. The effect are seen in wild-type strains and in three mutant strains with genetically altered period lengths. These results suggest the possible involvement of adenosine 3', 5'-monophosphate in the control of circadian rhythmicity."} {"id": "PMID:173019", "title": "Immunosurveillance of naturally occurring feline leukemia.", "content": "When compared to their housemates that subsequently developed leukemia, cats that remained healthy had five-to tenfold higher (geometric mean) humoral antibody titers to the feline oncornavirus-associated cell membrane antigen. This is compatible with the application of the immunosurveillance hypothesis to the natural development of leukemia in an outbred mammalian species.", "contents": "Immunosurveillance of naturally occurring feline leukemia. When compared to their housemates that subsequently developed leukemia, cats that remained healthy had five-to tenfold higher (geometric mean) humoral antibody titers to the feline oncornavirus-associated cell membrane antigen. This is compatible with the application of the immunosurveillance hypothesis to the natural development of leukemia in an outbred mammalian species."} {"id": "PMID:173020", "title": "Tumorigenicity of mouse-human diploid hybrids in nude mice.", "content": "Somatic cell hybrids between normal mouse cells and simian virus 40 (SV40)-transformed human cells, which contained a diploid complement of mouse chromosomes and the human chromosome 7 carrying the genome of SV40, were tumorigenic in nude mice. One single copy of human chromosome 7 per hybrid cell appeared to be sufficient for the tumorigenicity of the hybrids.", "contents": "Tumorigenicity of mouse-human diploid hybrids in nude mice. Somatic cell hybrids between normal mouse cells and simian virus 40 (SV40)-transformed human cells, which contained a diploid complement of mouse chromosomes and the human chromosome 7 carrying the genome of SV40, were tumorigenic in nude mice. One single copy of human chromosome 7 per hybrid cell appeared to be sufficient for the tumorigenicity of the hybrids."} {"id": "PMID:173022", "title": "Estrogen target sites in the brain of the chick embryo.", "content": "Autoradiograms prepared from brains of chick embryos after injection of [3H]estradiol demonstrate the existence of target cells for estrogen in the medial preoptic and ventral hypothalamic regions as early as day 10 of incubation. Target cells also appear in telencephalic locations during later stages of embryonic development. These hormone-concentrating cells probably are the anatomical substrate for the formative action of sex steroids during embryonic life on certain brain functions such as control of sexual and aggressive behaviour and gonadotropin secretion.", "contents": "Estrogen target sites in the brain of the chick embryo. Autoradiograms prepared from brains of chick embryos after injection of [3H]estradiol demonstrate the existence of target cells for estrogen in the medial preoptic and ventral hypothalamic regions as early as day 10 of incubation. Target cells also appear in telencephalic locations during later stages of embryonic development. These hormone-concentrating cells probably are the anatomical substrate for the formative action of sex steroids during embryonic life on certain brain functions such as control of sexual and aggressive behaviour and gonadotropin secretion."} {"id": "PMID:173024", "title": "Hepatocellular carcinoma: a clinical study.", "content": "The clinical course of 40 patients with histologically proven hepatocellular carcinoma was reviewed. The majority had symptoms and signs suggesting abdominal malignancy; these included abdominal pain, weight loss, tenderness in the right upper quadrant, hepatomegaly, and fever. The most useful diagnostic tests were determination of serum alkaline phosphatase level, sodium sulfobromophthalein (Bromsulphalein) excretion, and liver scan. Prothrombin time and bilirubin levels were normal or only slightly elevated. Celiac angiography was helpful in determining the extent of the disease. Surgical exploration was done in 25% of the cases, but in only 5% was resection attempted. The grim prognosis is indicated by the fact that only 10% of patients were alive six months after admission to the hospital.", "contents": "Hepatocellular carcinoma: a clinical study. The clinical course of 40 patients with histologically proven hepatocellular carcinoma was reviewed. The majority had symptoms and signs suggesting abdominal malignancy; these included abdominal pain, weight loss, tenderness in the right upper quadrant, hepatomegaly, and fever. The most useful diagnostic tests were determination of serum alkaline phosphatase level, sodium sulfobromophthalein (Bromsulphalein) excretion, and liver scan. Prothrombin time and bilirubin levels were normal or only slightly elevated. Celiac angiography was helpful in determining the extent of the disease. Surgical exploration was done in 25% of the cases, but in only 5% was resection attempted. The grim prognosis is indicated by the fact that only 10% of patients were alive six months after admission to the hospital."} {"id": "PMID:173025", "title": "A study of serum lipoproteins and angiographic evidence of coronary artery disease.", "content": "Extensive serum lipid analyses, with specific emphasis on the concentration of serum beta and pre-beta-lipoproteins, were made on 93 patients who had a clinical diagnosis of angina pectoris and were undergoing coronary angiographic studies. Those individuals with abnormal angiographic evidence of obstructive coronary artery disease, including a group with a prior myocardial infarction, have almost uniformly elevated serum beta-lipoprotein levels when related to an arbitrary division based on the mean values for a \"normal\" adult population at a similar age level. Compared to serum cholesterol and serum triglycerides, the serum lipoprotein concentrations, specifically beta-lipoproteins, appear to be a more useful parameter for predicting the existence of coronary artery disease. Further studies relating clinical risk factors to coronary artery disease might be better approached by using angiography of coronary vessels rather than myocardial infarction or sudden death from coronary artery disease as an endpoint of morbid data.", "contents": "A study of serum lipoproteins and angiographic evidence of coronary artery disease. Extensive serum lipid analyses, with specific emphasis on the concentration of serum beta and pre-beta-lipoproteins, were made on 93 patients who had a clinical diagnosis of angina pectoris and were undergoing coronary angiographic studies. Those individuals with abnormal angiographic evidence of obstructive coronary artery disease, including a group with a prior myocardial infarction, have almost uniformly elevated serum beta-lipoprotein levels when related to an arbitrary division based on the mean values for a \"normal\" adult population at a similar age level. Compared to serum cholesterol and serum triglycerides, the serum lipoprotein concentrations, specifically beta-lipoproteins, appear to be a more useful parameter for predicting the existence of coronary artery disease. Further studies relating clinical risk factors to coronary artery disease might be better approached by using angiography of coronary vessels rather than myocardial infarction or sudden death from coronary artery disease as an endpoint of morbid data."} {"id": "PMID:173028", "title": "Localised myeloma with osteogenesis and Russell body formation.", "content": "A case of an osteosclerotic myeloma of the mandible is described. Bone formation took the form of prominent sunray spiculation and radiologically mimicked an osteosarcoma. No other well-documented solitary lesion of this type could be found in the English literature. In addition, this tumour contained an abundance of intracytoplasmic Russell bodies and also produced a paraprotein. The paraprotein peak disappeared after resection.", "contents": "Localised myeloma with osteogenesis and Russell body formation. A case of an osteosclerotic myeloma of the mandible is described. Bone formation took the form of prominent sunray spiculation and radiologically mimicked an osteosarcoma. No other well-documented solitary lesion of this type could be found in the English literature. In addition, this tumour contained an abundance of intracytoplasmic Russell bodies and also produced a paraprotein. The paraprotein peak disappeared after resection."} {"id": "PMID:173031", "title": "Portal and pancreatic vein catheterization with radioimmunologic determination of insulin.", "content": "Percutaneous transhepatic catheterization of the portal vein along with the catheterization of the aorta and the vena cava was performed in six patients, one of whom had hypoglycemic attacks due to Whipple's triad. Blood samples from different branches in the different vessel systems were withdrawn for radioimmunologic determination of insulin. By this method, preoperative localization of the insulin producing pancreatic islet cell tumor was su-cessfully performed. Multiple tumors as well as liver metastases were preoperatively excluded. Recatheterization and blood sampling for radioimmunologic determination of insulin was performed postoperatively to verify the radicality of the operation. Insulin concentrations from the hypoglycemic patients were compared with those of the patients without insulinoma and found to be significantly higher. The procedure is proposed as a useful method for localizing all types of gastrointestinal hormone producing primary or secondary tumors in which a method for hormone determination is available. The postoperative investigation is useful as a check of the operation performed and as a follow-up examination for the early diagnosis of recurrence.", "contents": "Portal and pancreatic vein catheterization with radioimmunologic determination of insulin. Percutaneous transhepatic catheterization of the portal vein along with the catheterization of the aorta and the vena cava was performed in six patients, one of whom had hypoglycemic attacks due to Whipple's triad. Blood samples from different branches in the different vessel systems were withdrawn for radioimmunologic determination of insulin. By this method, preoperative localization of the insulin producing pancreatic islet cell tumor was su-cessfully performed. Multiple tumors as well as liver metastases were preoperatively excluded. Recatheterization and blood sampling for radioimmunologic determination of insulin was performed postoperatively to verify the radicality of the operation. Insulin concentrations from the hypoglycemic patients were compared with those of the patients without insulinoma and found to be significantly higher. The procedure is proposed as a useful method for localizing all types of gastrointestinal hormone producing primary or secondary tumors in which a method for hormone determination is available. The postoperative investigation is useful as a check of the operation performed and as a follow-up examination for the early diagnosis of recurrence."} {"id": "PMID:173032", "title": "Hepatocyte perfusion within a centrifuge.", "content": "A centrifuge, as used in blood banks for washing erythrocytes, is shown to be a good perfusion chamber for hepatocyte suspensions being evaluated for potential extracorporeal liver support. The perfusate was cell-free oxygenated--pO2 300 millimeters of mercury--plasma, serum or tissue culture medium. A centrifuge that requires intermittent perfusion cannot deliver sufficient oxygen to maintain prolonged viability. A continuous flow unit can, at a flow of 800 milliliters per minute, support most functions of 100 grams of hepatocytes for six hours and some function for 12 hours. Metabolism of 2-14C tagged pyruvate to 14CO2 is the most useful sensitive measurement of liver function in this system. It is concluded that a centrifuge allowing a constant perfusion of oxygenated plasma into hepatocytes kept within the unit by centrifugal force is a suitable base for extracorporeal liver support.", "contents": "Hepatocyte perfusion within a centrifuge. A centrifuge, as used in blood banks for washing erythrocytes, is shown to be a good perfusion chamber for hepatocyte suspensions being evaluated for potential extracorporeal liver support. The perfusate was cell-free oxygenated--pO2 300 millimeters of mercury--plasma, serum or tissue culture medium. A centrifuge that requires intermittent perfusion cannot deliver sufficient oxygen to maintain prolonged viability. A continuous flow unit can, at a flow of 800 milliliters per minute, support most functions of 100 grams of hepatocytes for six hours and some function for 12 hours. Metabolism of 2-14C tagged pyruvate to 14CO2 is the most useful sensitive measurement of liver function in this system. It is concluded that a centrifuge allowing a constant perfusion of oxygenated plasma into hepatocytes kept within the unit by centrifugal force is a suitable base for extracorporeal liver support."} {"id": "PMID:173033", "title": "Diagnosis of human fetal abnormalities by fetography.", "content": "Being able to detect fetal abnormalities that may be associated with hydramnios would be extremely useful, especially when diabetes mellitus, Rh isoimmunization, and multiple pregnancy are ruled out. For this purpose the new technique of fetography, consisting of injecting a small amount of 2 radioque media (liposoluble and hydrosoluble), was used. Four out of 6 fetuses were correctly predicted to be abnormal. They were 1 case of esophageal atresia, 1 of suspicious chromosomal abnormality (after birth it was confirmed as having the Smith-Lemli-Opitz syndrome), and 2 of trisomy 18. It is felt that this simple technique should be used as an aid to the obstetrician faced with the problem of determining the basis of unexplained hydramnios.", "contents": "Diagnosis of human fetal abnormalities by fetography. Being able to detect fetal abnormalities that may be associated with hydramnios would be extremely useful, especially when diabetes mellitus, Rh isoimmunization, and multiple pregnancy are ruled out. For this purpose the new technique of fetography, consisting of injecting a small amount of 2 radioque media (liposoluble and hydrosoluble), was used. Four out of 6 fetuses were correctly predicted to be abnormal. They were 1 case of esophageal atresia, 1 of suspicious chromosomal abnormality (after birth it was confirmed as having the Smith-Lemli-Opitz syndrome), and 2 of trisomy 18. It is felt that this simple technique should be used as an aid to the obstetrician faced with the problem of determining the basis of unexplained hydramnios."} {"id": "PMID:173043", "title": "Electron microscopic observation of inclusion bodies in plasma cells of multiple myeloma and Waldenstr\u00f6m's macroglobulinemia.", "content": "Intracellular inclusion bodies in the plasma cells were sought by electron microscopy in 32 cases of multiple myeloma and 3 of Waldenstr\u00f6m's macroglobulinemia. In some cases, round shaped intranuclear inclusions and intranuclear fibrillar bundles were observed. In other cases, Russell bodies and crystalline structures were found in the cisternae of rough surfaced endoplasmic reticulum (rER), and dense bodies, myelin-like structures, fibrillar formations, polysome lamellae complexes, crystalline structures, virus-like particles and phagocytosis were observed in the cytoplasm of plasma cells. The detailed ultrastructure of these inclusions was described, and their functional significance, origin and appearance rate were discussed. Finally, the presence of true viral particles in the plasma cells was ruled out.", "contents": "Electron microscopic observation of inclusion bodies in plasma cells of multiple myeloma and Waldenstr\u00f6m's macroglobulinemia. Intracellular inclusion bodies in the plasma cells were sought by electron microscopy in 32 cases of multiple myeloma and 3 of Waldenstr\u00f6m's macroglobulinemia. In some cases, round shaped intranuclear inclusions and intranuclear fibrillar bundles were observed. In other cases, Russell bodies and crystalline structures were found in the cisternae of rough surfaced endoplasmic reticulum (rER), and dense bodies, myelin-like structures, fibrillar formations, polysome lamellae complexes, crystalline structures, virus-like particles and phagocytosis were observed in the cytoplasm of plasma cells. The detailed ultrastructure of these inclusions was described, and their functional significance, origin and appearance rate were discussed. Finally, the presence of true viral particles in the plasma cells was ruled out."} {"id": "PMID:173044", "title": "(3H)-estradiol binding by chick liver nuclear extracts: mechanism of increase in binding following estradiol injection.", "content": "Specific high affinity binding of [3H]-estradiol by 0.5 M KCl extracts of chick liver nuclei is substantially increased by estradiol injection of the immature chick. The effect is observed shortly after estradiol injection, while the estradiol-induced production of serum phosphoproteins (vitellogenic response) is not detectable until about 24 hr. Cycloheximide given 90 min before estradiol inhibits the increase in nuclear binding for 12-15 hr. At 24-48 hr the levels of nuclear binding are similar to those in the estradiol-treated animals not given cycloheximide, but serum phosphoprotein levels are depressed by about 80% at 48 hr. By 75 hr however the serum of the cycloheximide-treated estrogenized chicks contains about twice as much phosphoprotein as does serum of chicks given estradiol alone. It is suggested that the inhibition of protein synthesis for 12-15 hr delays the vitellogenic response until sufficient levels of nuclear [3H]-estradiol binding protein can be synthesized. A correlation between the levels of nuclear [3H]-estradiol binding at 24 hr and phosphoprotein at 48 hr is shown in a dose-response experiment. In vitro, nafoxidine-HCl (Upjohn 11,100 A) inhibits binding of [3H]-estradiol by the chick liver nuclear extracts. In vivo, a single injection of nafoxidine with estradiol inhibits phosphoprotein production. Injection of nafoxidine alone results in a small but significant increase in [3H]-estradiol binding by nuclear extracts, but it is not estrogenic. A possible interpretation is that nafoxidine transfers low levels of a putative cytosol receptor to the nucleus, but is unable to induce the amplification mechanism required to give the levels of nuclear estradiol-binding protein needed for the vitellogenic response.", "contents": "(3H)-estradiol binding by chick liver nuclear extracts: mechanism of increase in binding following estradiol injection. Specific high affinity binding of [3H]-estradiol by 0.5 M KCl extracts of chick liver nuclei is substantially increased by estradiol injection of the immature chick. The effect is observed shortly after estradiol injection, while the estradiol-induced production of serum phosphoproteins (vitellogenic response) is not detectable until about 24 hr. Cycloheximide given 90 min before estradiol inhibits the increase in nuclear binding for 12-15 hr. At 24-48 hr the levels of nuclear binding are similar to those in the estradiol-treated animals not given cycloheximide, but serum phosphoprotein levels are depressed by about 80% at 48 hr. By 75 hr however the serum of the cycloheximide-treated estrogenized chicks contains about twice as much phosphoprotein as does serum of chicks given estradiol alone. It is suggested that the inhibition of protein synthesis for 12-15 hr delays the vitellogenic response until sufficient levels of nuclear [3H]-estradiol binding protein can be synthesized. A correlation between the levels of nuclear [3H]-estradiol binding at 24 hr and phosphoprotein at 48 hr is shown in a dose-response experiment. In vitro, nafoxidine-HCl (Upjohn 11,100 A) inhibits binding of [3H]-estradiol by the chick liver nuclear extracts. In vivo, a single injection of nafoxidine with estradiol inhibits phosphoprotein production. Injection of nafoxidine alone results in a small but significant increase in [3H]-estradiol binding by nuclear extracts, but it is not estrogenic. A possible interpretation is that nafoxidine transfers low levels of a putative cytosol receptor to the nucleus, but is unable to induce the amplification mechanism required to give the levels of nuclear estradiol-binding protein needed for the vitellogenic response."} {"id": "PMID:173045", "title": "Estrogen receptor in rat liver and its dependence on prolactin.", "content": "Estrogen receptor is shown to be present in the livers of adult rats. The receptor binds estradiol-17beta with a Kd of 1 x 10(-10) M and sediments at 8 S in sucrose gradients. Other estrogens and anti-estrogens compete for estradiol binding, while nonestrogenic steroids do not. Receptor levels fall dramatically after hypophysectomy, but can be partially restored within 18 hours by a single injection of prolactin. It is known that prolactin critically regulates the level of its own receptor in the liver, and we now suggest that it also exerts a primary control over the availability of liver estrogen receptor.", "contents": "Estrogen receptor in rat liver and its dependence on prolactin. Estrogen receptor is shown to be present in the livers of adult rats. The receptor binds estradiol-17beta with a Kd of 1 x 10(-10) M and sediments at 8 S in sucrose gradients. Other estrogens and anti-estrogens compete for estradiol binding, while nonestrogenic steroids do not. Receptor levels fall dramatically after hypophysectomy, but can be partially restored within 18 hours by a single injection of prolactin. It is known that prolactin critically regulates the level of its own receptor in the liver, and we now suggest that it also exerts a primary control over the availability of liver estrogen receptor."} {"id": "PMID:173046", "title": "Metabolism of dehydroepiandrosterone by hormone dependent and hormone independent human breast carcinoma.", "content": "The metabolism of 7alpha-3H-dehydroepiandrosterone was studied in six human breast carcinomas in vitro. All mammary tumors transformed DHA to testosterone, dihydrotestosterone, 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3,17-dione. Of the tumors investigated, three estrogen receptor-negative tumors converted DHA to estradiol and only one estrogen receptor-positive tumor produced estradiol from DHA. Observations on the relationship of androgen metabolism and hormone dependency are discussed.", "contents": "Metabolism of dehydroepiandrosterone by hormone dependent and hormone independent human breast carcinoma. The metabolism of 7alpha-3H-dehydroepiandrosterone was studied in six human breast carcinomas in vitro. All mammary tumors transformed DHA to testosterone, dihydrotestosterone, 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3,17-dione. Of the tumors investigated, three estrogen receptor-negative tumors converted DHA to estradiol and only one estrogen receptor-positive tumor produced estradiol from DHA. Observations on the relationship of androgen metabolism and hormone dependency are discussed."} {"id": "PMID:173048", "title": "[Experimental and clinical evaluation of stomatological cleaning agents with special reference to the Eladent prosthesis cleaner].", "content": "The experimental and clinical testing of certain denture cleaners, viz., Eladent, Kukident and Steradent, yielded identical good results. As far as possible, Eladent should be dissolved in warm water (35-40 degrees C). In this case, the tablets will dissolve within 15-20 minutes. For immediate cleaning, the tablets may be dissolved within 1 or 2 minutes by raising the water temperature at 50 degrees C. No striking immediate effect can be expected from this cleaner in case of stained dentures which have been worn for many years. The cleaner improves little by little the hygienic condition of the denture. It is recommended to apply the cleaning tablets immediately after insertion of the prosthesis at regular intervals. In this way, soft deposits and plaques will no longer adhere and cause the formation of hard deposits.", "contents": "[Experimental and clinical evaluation of stomatological cleaning agents with special reference to the Eladent prosthesis cleaner]. The experimental and clinical testing of certain denture cleaners, viz., Eladent, Kukident and Steradent, yielded identical good results. As far as possible, Eladent should be dissolved in warm water (35-40 degrees C). In this case, the tablets will dissolve within 15-20 minutes. For immediate cleaning, the tablets may be dissolved within 1 or 2 minutes by raising the water temperature at 50 degrees C. No striking immediate effect can be expected from this cleaner in case of stained dentures which have been worn for many years. The cleaner improves little by little the hygienic condition of the denture. It is recommended to apply the cleaning tablets immediately after insertion of the prosthesis at regular intervals. In this way, soft deposits and plaques will no longer adhere and cause the formation of hard deposits."} {"id": "PMID:173059", "title": "Physiological properties of vertebrate nerve cells in tissue culture.", "content": "Vertebrate neurons in tissue culture are providing us with a new model system for studying the complex events which occur during neuronal differentiation, synaptogenesis, and neural network formation. It is already apparent that dissociated embryo neurons are capable of differentiating both morphologically and physiologically along predetermined lines in the absence of external influences. These neurons can form new connections with one another but retain some specificity in their selections. Both simple and complex neural networks can be seen. At the present time, the development of the invitro model system is just being explored. The potential value of a system of this kind at a variety of investigative levels should be appreciated. Questions of a fundamental nature in neurobiology, such as how synapses form, what rules govern such interaction, how cells recognize one another, and the nature of the basic two-, three-, or four-cell circuits that comprise the more complex neurons tissue can be approached with this system. Studies of the neurons and synapses themselves can lead to a more basic understanding of vertebrate nervous system functioning. The development of certain pathophysiological processes and the effects of neuroactive drugs on vertebrate neurons may be studied at the cellular level. Finally, the basic mechanism of some genetic abnormalities which produce abnormal nervous structure and function may be more easily determined in a simplified in vitro model than in the intact central nervous system. The value of any model is not inherent in the elegance of the model itseld, but only in its ability to suggest answers to fundamental questions about the system being modeled. Many fundamental questions about brain mechanisms in mental retardation remain unanswered. Perhaps some day the model of nerve cells in tissue culture will bring us closer to the answers to these questions.", "contents": "Physiological properties of vertebrate nerve cells in tissue culture. Vertebrate neurons in tissue culture are providing us with a new model system for studying the complex events which occur during neuronal differentiation, synaptogenesis, and neural network formation. It is already apparent that dissociated embryo neurons are capable of differentiating both morphologically and physiologically along predetermined lines in the absence of external influences. These neurons can form new connections with one another but retain some specificity in their selections. Both simple and complex neural networks can be seen. At the present time, the development of the invitro model system is just being explored. The potential value of a system of this kind at a variety of investigative levels should be appreciated. Questions of a fundamental nature in neurobiology, such as how synapses form, what rules govern such interaction, how cells recognize one another, and the nature of the basic two-, three-, or four-cell circuits that comprise the more complex neurons tissue can be approached with this system. Studies of the neurons and synapses themselves can lead to a more basic understanding of vertebrate nervous system functioning. The development of certain pathophysiological processes and the effects of neuroactive drugs on vertebrate neurons may be studied at the cellular level. Finally, the basic mechanism of some genetic abnormalities which produce abnormal nervous structure and function may be more easily determined in a simplified in vitro model than in the intact central nervous system. The value of any model is not inherent in the elegance of the model itseld, but only in its ability to suggest answers to fundamental questions about the system being modeled. Many fundamental questions about brain mechanisms in mental retardation remain unanswered. Perhaps some day the model of nerve cells in tissue culture will bring us closer to the answers to these questions."} {"id": "PMID:173062", "title": "Studies on the molecular defect in galactosemia.", "content": "The galactose metabolic pathway and some of the consequences of deficient galactokinase or gal-1-P uridyltransferase activity have been discussed. The existence of CRM in transferase deficiency galactosemia is presented as evidence that this disease is the result of a structural gene mutation. The finding of both quantitative and qualitative variation in transferase CRM among different galactosemic patients argues that genetic heterogeneity exists within this group. Data supporting a Ping-Pong mechanism of action for human transferase reaction is proposed.", "contents": "Studies on the molecular defect in galactosemia. The galactose metabolic pathway and some of the consequences of deficient galactokinase or gal-1-P uridyltransferase activity have been discussed. The existence of CRM in transferase deficiency galactosemia is presented as evidence that this disease is the result of a structural gene mutation. The finding of both quantitative and qualitative variation in transferase CRM among different galactosemic patients argues that genetic heterogeneity exists within this group. Data supporting a Ping-Pong mechanism of action for human transferase reaction is proposed."} {"id": "PMID:173063", "title": "[Influence of cortisone on the levels of pyruvic and lactic acids and the activity of the enzymes of gluconeogenesis in the tissues of newborn and adult animals].", "content": "There are considerable changes in the lactic and pyruvic acid contents and fructoso-1,6-diphosphatase and glucose-6-phosphatase activities in some tissues of newborn and adult guinea pigs and rabbits 24 hours after cortisone-acetate (2 mg per 100 g of body weight) injection. In the newborn animals of both species the hormone causes a decrease in the lactic and pyruvic acid concentrations and an increase in fructoso-1,6-diphosphatase activity when in the adult ones--an increase in the lactic and pyruvic acid levels and in the glucose-6-phosphatase. In the liver and kidney cortex of adult animals as compared to the newborn ones the fructoso-1,6-diphosphatase activity is significantly increased and in other tissues under study it is decreased. Certain species differences in lactic and pyruvic acid contents and in the activities of both enzymes as well as in the character of their changes under cortisone influence are found.", "contents": "[Influence of cortisone on the levels of pyruvic and lactic acids and the activity of the enzymes of gluconeogenesis in the tissues of newborn and adult animals]. There are considerable changes in the lactic and pyruvic acid contents and fructoso-1,6-diphosphatase and glucose-6-phosphatase activities in some tissues of newborn and adult guinea pigs and rabbits 24 hours after cortisone-acetate (2 mg per 100 g of body weight) injection. In the newborn animals of both species the hormone causes a decrease in the lactic and pyruvic acid concentrations and an increase in fructoso-1,6-diphosphatase activity when in the adult ones--an increase in the lactic and pyruvic acid levels and in the glucose-6-phosphatase. In the liver and kidney cortex of adult animals as compared to the newborn ones the fructoso-1,6-diphosphatase activity is significantly increased and in other tissues under study it is decreased. Certain species differences in lactic and pyruvic acid contents and in the activities of both enzymes as well as in the character of their changes under cortisone influence are found."} {"id": "PMID:173064", "title": "[Influence of muscular activity on changes in the metabolism of tendotomized muscle].", "content": "The muscular activity is established to inhibit the development of atrophic and dystrophic changes and accelerates the restoration of normal biochemical status in a tendotomized muscle. Surgical desympathization does not remove this effect of the increased muscular activity. However surgical desympathization lowers the degree of compensatory biochemical changes in the symmetrical intact muscle of the other leg. Atrophical phenomena is little expressed and dystrophical changes are absent in the tendotomized trained muscles.", "contents": "[Influence of muscular activity on changes in the metabolism of tendotomized muscle]. The muscular activity is established to inhibit the development of atrophic and dystrophic changes and accelerates the restoration of normal biochemical status in a tendotomized muscle. Surgical desympathization does not remove this effect of the increased muscular activity. However surgical desympathization lowers the degree of compensatory biochemical changes in the symmetrical intact muscle of the other leg. Atrophical phenomena is little expressed and dystrophical changes are absent in the tendotomized trained muscles."} {"id": "PMID:173069", "title": "[Abdominoanal resection of the rectum with a lowering of different sections of the left half of the colon].", "content": "In tumor localization at the level of 7--12 cm aside from the anus the authors performed 168 abdominoanal resections of the rectum with descending of different portions of the left colon. Among these patients in 126 subjects descending of the sigmoid in the anal canal was performed, in 30 of the splenic angle of the transverse colon, and in 12 of a proximal portion of the descending left colon. Some characteristic features of surgery for descending of different portions of the left colon are described.", "contents": "[Abdominoanal resection of the rectum with a lowering of different sections of the left half of the colon]. In tumor localization at the level of 7--12 cm aside from the anus the authors performed 168 abdominoanal resections of the rectum with descending of different portions of the left colon. Among these patients in 126 subjects descending of the sigmoid in the anal canal was performed, in 30 of the splenic angle of the transverse colon, and in 12 of a proximal portion of the descending left colon. Some characteristic features of surgery for descending of different portions of the left colon are described."} {"id": "PMID:173070", "title": "Dose response to a single injection of azoxymethane in rats. Induction of tumors in the gastrointestinal tract, auditory sebaceous glands, kidney, liver and preputial gland.", "content": "Male Fischer rats, 6 weeks old, were injected once with one of five doses of azoxymethane. There was a dose response to the carcinogen as determined by weight gain and tumor induction. Rats given the three highest doses developed tumors of the gastrointestinal tract, auditory sebaceous glands, kidney, liver, and preputial gland, whereas rats receiving the lowest doses had tumors mainly of the intestine. Chronic liver lesions in high-dose rats were cirrhosis with megalocytosis, mild fibrosis, nodular hepatocellular hyperplasia, and hyperplasia of bile ductules.", "contents": "Dose response to a single injection of azoxymethane in rats. Induction of tumors in the gastrointestinal tract, auditory sebaceous glands, kidney, liver and preputial gland. Male Fischer rats, 6 weeks old, were injected once with one of five doses of azoxymethane. There was a dose response to the carcinogen as determined by weight gain and tumor induction. Rats given the three highest doses developed tumors of the gastrointestinal tract, auditory sebaceous glands, kidney, liver, and preputial gland, whereas rats receiving the lowest doses had tumors mainly of the intestine. Chronic liver lesions in high-dose rats were cirrhosis with megalocytosis, mild fibrosis, nodular hepatocellular hyperplasia, and hyperplasia of bile ductules."} {"id": "PMID:173065", "title": "[Noncoenzymic function of vitamin PP].", "content": "The article deals with the experimental data of the authors and those from literature on interrelation between NAD and DNA metabolism in hepatocytes and the role of nuclear NAD-glycohydrolase and NAD-pyrophosphorylase in these processes. Considerable attention is paid to the information on biosynthesis, structure and biochemical functions of poly(ADPR)--a new polymer formed in eucariots nuclei from NAD. The data on the effects of vitamin PP and its biologically active derivative--NAD on DNA synthesis, proliferation of cells and on their genic activity are presented and discussed from modern view points on noncoenzymatic functions of this vitamin.", "contents": "[Noncoenzymic function of vitamin PP]. The article deals with the experimental data of the authors and those from literature on interrelation between NAD and DNA metabolism in hepatocytes and the role of nuclear NAD-glycohydrolase and NAD-pyrophosphorylase in these processes. Considerable attention is paid to the information on biosynthesis, structure and biochemical functions of poly(ADPR)--a new polymer formed in eucariots nuclei from NAD. The data on the effects of vitamin PP and its biologically active derivative--NAD on DNA synthesis, proliferation of cells and on their genic activity are presented and discussed from modern view points on noncoenzymatic functions of this vitamin."} {"id": "PMID:173071", "title": "Naturally occurring intracytoplasmic inclusions in the canine exocrine pancreas.", "content": "Bodies similar to acidophilic intracytoplasmic inclusions were found by light microscopy in the pancreatic acinar cells of 56 of 174 (32%) healthy male and female purebred Beagles and 14 of 97 (14%) of healthy male mongrel dogs. The inclusions were ovoid, acidophilic and often granular with basophilic particulates. Many seemed to be enclosed within halos of various widths. Electron microscopically the inclusions consisted of whorls of rough endoplasmic reticulum, vacuoles, and cytoplasmic organelles in various stages of decomposition. These inclusion bodies were interpreted as evidence of focal intracytoplasmic degradation. They appeared similar to the dense ribosomal autophagic vacuoles, hitherto described only in association with various experimental procedures.", "contents": "Naturally occurring intracytoplasmic inclusions in the canine exocrine pancreas. Bodies similar to acidophilic intracytoplasmic inclusions were found by light microscopy in the pancreatic acinar cells of 56 of 174 (32%) healthy male and female purebred Beagles and 14 of 97 (14%) of healthy male mongrel dogs. The inclusions were ovoid, acidophilic and often granular with basophilic particulates. Many seemed to be enclosed within halos of various widths. Electron microscopically the inclusions consisted of whorls of rough endoplasmic reticulum, vacuoles, and cytoplasmic organelles in various stages of decomposition. These inclusion bodies were interpreted as evidence of focal intracytoplasmic degradation. They appeared similar to the dense ribosomal autophagic vacuoles, hitherto described only in association with various experimental procedures."} {"id": "PMID:173072", "title": "Tissue-steroid interactions in canine hormone-dependent tumours.", "content": "Mammary tumour tissue from two bitches and an anal adenoma from a dog were investigated for steroid receptor interaction. Both mammary tumours possessed cytoplasmic macromolecules sedimenting with coefficients of 4S and 8S that bound oestradiol-17beta. These receptors had molecular weights of approximately 60,000 and 180,000 respectively. Transfer of the oestrogen to the nucleus was shown and the presence of a 4-5S nuclear protein demonstrated. The anal adenoma had a cytoplasmic receptor, with a sedimentation value in a sucrose density gradient of 4-5S with respect to bovine serum albumin, that bound tritiated 5alpha-androstane-3alpha, 17alpha-diol. No affinity could be demonstrated for other C19-steroids examined. The significance of these findings in terms of the hormone dependence of the tumours investigated and the possible development of these studies to promote rational therapy in such cases is discussed.", "contents": "Tissue-steroid interactions in canine hormone-dependent tumours. Mammary tumour tissue from two bitches and an anal adenoma from a dog were investigated for steroid receptor interaction. Both mammary tumours possessed cytoplasmic macromolecules sedimenting with coefficients of 4S and 8S that bound oestradiol-17beta. These receptors had molecular weights of approximately 60,000 and 180,000 respectively. Transfer of the oestrogen to the nucleus was shown and the presence of a 4-5S nuclear protein demonstrated. The anal adenoma had a cytoplasmic receptor, with a sedimentation value in a sucrose density gradient of 4-5S with respect to bovine serum albumin, that bound tritiated 5alpha-androstane-3alpha, 17alpha-diol. No affinity could be demonstrated for other C19-steroids examined. The significance of these findings in terms of the hormone dependence of the tumours investigated and the possible development of these studies to promote rational therapy in such cases is discussed."} {"id": "PMID:173067", "title": "Synovial sarcoma of the larynx.", "content": "There have been several reports in the literature2-5 of synovial sarcomas of the head and neck. The consensus of these authors is that the tumor is not as aggressive in this localization as in the extremities, where the recurrence rate is 60% to 70%, and the five-year long-term follow-up of such cases should be made available. Thereby, a reasonably clear and effective modality of treatment could be recommoneded.", "contents": "Synovial sarcoma of the larynx. There have been several reports in the literature2-5 of synovial sarcomas of the head and neck. The consensus of these authors is that the tumor is not as aggressive in this localization as in the extremities, where the recurrence rate is 60% to 70%, and the five-year long-term follow-up of such cases should be made available. Thereby, a reasonably clear and effective modality of treatment could be recommoneded."} {"id": "PMID:173066", "title": "[Functional exchange of metabolic regulators in endocrinology and neurochemistry].", "content": "On the basis of the authors and their collaborators studies and the data of other investigators, the paper deals with significance and development of the idea of the role in the regulation of the processes and functions not only of unchanged adrenergic hormones-mediators (catecholamines) but also of the products of their metabolism as well as of those ways by which this metabolism occurs. Diversity in the processes of catecholamines and other hormones transformation makes it possible the shunting of this metabolism from one ways to others, that has an effect on many key enzymes of the intracellular metabolism. The products of quinoid and monoaminoxidase transformation of catecholamines affect directly the enzymatic processes and may change the character and intensity of the subsequent and simultaneous effect of the native hormones-mediators. The data obtained when studying adrenaline and noradrenaline metabolism may be extrapolated to certain aspects of the action mechanism of other hormones and mediators of nervous processes. An attempt is made to generalize theoretically the data on the role of hormones-mediators of metabolism in the mechanism of their action with the idea of \"induced fit\" of the enzymes and with certain problems of biochemistry of the effector cells receptors.", "contents": "[Functional exchange of metabolic regulators in endocrinology and neurochemistry]. On the basis of the authors and their collaborators studies and the data of other investigators, the paper deals with significance and development of the idea of the role in the regulation of the processes and functions not only of unchanged adrenergic hormones-mediators (catecholamines) but also of the products of their metabolism as well as of those ways by which this metabolism occurs. Diversity in the processes of catecholamines and other hormones transformation makes it possible the shunting of this metabolism from one ways to others, that has an effect on many key enzymes of the intracellular metabolism. The products of quinoid and monoaminoxidase transformation of catecholamines affect directly the enzymatic processes and may change the character and intensity of the subsequent and simultaneous effect of the native hormones-mediators. The data obtained when studying adrenaline and noradrenaline metabolism may be extrapolated to certain aspects of the action mechanism of other hormones and mediators of nervous processes. An attempt is made to generalize theoretically the data on the role of hormones-mediators of metabolism in the mechanism of their action with the idea of \"induced fit\" of the enzymes and with certain problems of biochemistry of the effector cells receptors."} {"id": "PMID:173074", "title": "[Complement fixation reaction (CFR) in adenovirus infections of calves].", "content": "Studied was the complement-fixation reaction in the diagnosis of the adenovirus infections in calves. It was found that the test is specific and sensitive. A virus suspension of tissue cultures was used as an antigen, its titer varying from 1:8 up to 1:16. Specific complement-fixing antibodies were detected mainly in survivals at serum dilution of up to 1:64. Specific antibodies were established in undiluted sera too taken from animals of infected herds. In some of the tested sera there were both complement-fixing and precipitating antibodies. In calves treated with a live vaccine against adenoviruses the dynamics of the complement-fixing antibodies was followed up.", "contents": "[Complement fixation reaction (CFR) in adenovirus infections of calves]. Studied was the complement-fixation reaction in the diagnosis of the adenovirus infections in calves. It was found that the test is specific and sensitive. A virus suspension of tissue cultures was used as an antigen, its titer varying from 1:8 up to 1:16. Specific complement-fixing antibodies were detected mainly in survivals at serum dilution of up to 1:64. Specific antibodies were established in undiluted sera too taken from animals of infected herds. In some of the tested sera there were both complement-fixing and precipitating antibodies. In calves treated with a live vaccine against adenoviruses the dynamics of the complement-fixing antibodies was followed up."} {"id": "PMID:173075", "title": "[Adaptation and cultivation of the Perego strain of ovine smallpox virus in tissue culture and an evaluation of its immunogenic properties].", "content": "The strain Perego of the sheep pox virus, used for the production of the ovinized vaccine in this country, was adapted and cultured in tissue cultures of lamb testes. A total of ten passages in succession of the virus were performed with the manifestation of a characteristic cytopathic effect in the cultures. The titer of the virus was found to be within the range of 10(3.5)CPE50, for the initial passages, to 10(4.5)CPE50, for the final passages. The activity and harmlessness of the virus was tested on sheep. The inoculated 14 sheep with one vaccinal dose each, containing 100 CPE50, and two sheep treated with tenfold higher dose of the virus showed that sheep in general tolerate well the rates at which the virus was applied within the range cited. The general state of the sheep did not exhibit deviations, however, the animals' body temperature rose, and there were reactions at the site of the inoculation. Serum-neutralizing antibodies were established in the blood of sheep one month following vaccination.", "contents": "[Adaptation and cultivation of the Perego strain of ovine smallpox virus in tissue culture and an evaluation of its immunogenic properties]. The strain Perego of the sheep pox virus, used for the production of the ovinized vaccine in this country, was adapted and cultured in tissue cultures of lamb testes. A total of ten passages in succession of the virus were performed with the manifestation of a characteristic cytopathic effect in the cultures. The titer of the virus was found to be within the range of 10(3.5)CPE50, for the initial passages, to 10(4.5)CPE50, for the final passages. The activity and harmlessness of the virus was tested on sheep. The inoculated 14 sheep with one vaccinal dose each, containing 100 CPE50, and two sheep treated with tenfold higher dose of the virus showed that sheep in general tolerate well the rates at which the virus was applied within the range cited. The general state of the sheep did not exhibit deviations, however, the animals' body temperature rose, and there were reactions at the site of the inoculation. Serum-neutralizing antibodies were established in the blood of sheep one month following vaccination."} {"id": "PMID:173084", "title": "[Metabolism of nucleic acids in normal, regenerating and neoplastic tissues of the liver].", "content": "Under study was the kinetic growth of three hepatomas-22A, 60 and 46, characterized by a various degree of differentiation. There was found a correlation between the degree of differentiation and parameters of the hepatomas growth. For the hepatomas a correlation between the DNA content and rate of growth was observed, for hepatoma 46 a value of the DNA content proved to be near to that of normal liver. Moreover, in a regenerating liver the DNA content is the same as normal, that indicates the difference between normal and neoplastic actively proliferating tissues. The processes of DNA synthesis, studied by thymidine-C14 incorporation, showed a linear correlation with the rate of growth in regenerating, normal and neoplastic tissues. The ratio RNA/DNA in tumors is regularly decreased with respect to normal liver (a linear correlation between RNA/DNA and the maximum rate of growth). In a regenerating liver the ratio is high. Variations in the ratio RNA/DNA reflect changes in the functional activity and related disorders in the metabolism of nucleic acids in hepatomas. There was found a suppressed DNA decomposition in autolysis of homogenates from hepatoma tissues. It is essential to note that in a minimum deviated hepatoma some inhibition of the DNA decomposition is the only observed disorder in the nucleic acids metabolism. Spin-labelled DNA preparations of tissues under study were obtained. The presence of structural differences between separate DNA samples has been demonstrated.", "contents": "[Metabolism of nucleic acids in normal, regenerating and neoplastic tissues of the liver]. Under study was the kinetic growth of three hepatomas-22A, 60 and 46, characterized by a various degree of differentiation. There was found a correlation between the degree of differentiation and parameters of the hepatomas growth. For the hepatomas a correlation between the DNA content and rate of growth was observed, for hepatoma 46 a value of the DNA content proved to be near to that of normal liver. Moreover, in a regenerating liver the DNA content is the same as normal, that indicates the difference between normal and neoplastic actively proliferating tissues. The processes of DNA synthesis, studied by thymidine-C14 incorporation, showed a linear correlation with the rate of growth in regenerating, normal and neoplastic tissues. The ratio RNA/DNA in tumors is regularly decreased with respect to normal liver (a linear correlation between RNA/DNA and the maximum rate of growth). In a regenerating liver the ratio is high. Variations in the ratio RNA/DNA reflect changes in the functional activity and related disorders in the metabolism of nucleic acids in hepatomas. There was found a suppressed DNA decomposition in autolysis of homogenates from hepatoma tissues. It is essential to note that in a minimum deviated hepatoma some inhibition of the DNA decomposition is the only observed disorder in the nucleic acids metabolism. Spin-labelled DNA preparations of tissues under study were obtained. The presence of structural differences between separate DNA samples has been demonstrated."} {"id": "PMID:173085", "title": "[Functional state of the adrenal cortex in patients with cancer of the rectum].", "content": "The level of 17-ketosteroids and 17-ketogenic steroids in the diurnal urine was determined in 70 patients with rectal cancer prior to and after ACTH administration. In most patients the initial excretion of the steroids under study was found to be decreased. 17-ketosteroids excretion is reduced more frequently in patients over 50 years of age and in females. In a predominant number of patients functional reserves of the adrenal cortex are decreased.", "contents": "[Functional state of the adrenal cortex in patients with cancer of the rectum]. The level of 17-ketosteroids and 17-ketogenic steroids in the diurnal urine was determined in 70 patients with rectal cancer prior to and after ACTH administration. In most patients the initial excretion of the steroids under study was found to be decreased. 17-ketosteroids excretion is reduced more frequently in patients over 50 years of age and in females. In a predominant number of patients functional reserves of the adrenal cortex are decreased."} {"id": "PMID:173087", "title": "[Serologic diagnosis of brain tumors using Clostridium butyrium spores (experimental and clinical studies)].", "content": "Spores of the Clostridium butyrium M 55 strain, introuduced intravenously, proliferate selectivity in tumours of individual with newgrowths forming bacilli and then multiply evoking the appearance of antibacillary antibodies. In persons with no tumours there emerge only antispore antibodies. Since the spores and bacilli of this strain have antigens of a different nature their antibodies are encountered separately. The finding of antibacillary antibodies following injection of spores thus serves as an indirect proof for the presence of a malignant tumour. In experiments on animals (rats) with neurogenic tumours induced with ethylnitosole urea and also in patients with brain tumours this phenomenon has been studied in detail.", "contents": "[Serologic diagnosis of brain tumors using Clostridium butyrium spores (experimental and clinical studies)]. Spores of the Clostridium butyrium M 55 strain, introuduced intravenously, proliferate selectivity in tumours of individual with newgrowths forming bacilli and then multiply evoking the appearance of antibacillary antibodies. In persons with no tumours there emerge only antispore antibodies. Since the spores and bacilli of this strain have antigens of a different nature their antibodies are encountered separately. The finding of antibacillary antibodies following injection of spores thus serves as an indirect proof for the presence of a malignant tumour. In experiments on animals (rats) with neurogenic tumours induced with ethylnitosole urea and also in patients with brain tumours this phenomenon has been studied in detail."} {"id": "PMID:173088", "title": "[Diabetogenic and atherogenic effects of glucose].", "content": "Tests were set up on 59 albino male-rats with reproduced functional overstress and depletion of the insular system of the pancreas thorough a long-term (for 50, 100 days) peroral introduction of glucose (2 g/100 g body weight, every other day) and with and alloxan-induced diabetes (achieved by poisoning the animals with a 2.5% alloxan solution, 15 mg/100 g administered in a single dose intraperitoneally). A comparison of the data obtained ascertained the presence of a number of similar pathobiochemical changes in the metabolism, viz. hyperglycemia, an increase of the free cholesterol fraction, a diminution of the bound cholesterol fraction and a fall of the insulin-like activity (ILA) in the blood serum, a rise in glycogen and beta-lipoproteids in the liver; morphologically--a reduced count of Langerhan's islands beta-cells, less intensive colouration of the specific granulation in their cytoplasma manifestations of vacuolar and granular dystrophy of the liver. Further tests were staged on 23 rabbits involving a long-term introduction of glucose (in amounts of 25 g/kg every other day) and a cholesterol-induced atherosclerosis (by administering 0.2 g/kg of cholesterol in oil, daily), which also showed similar changes in the figures of the carbohydrate and fat-lipoids metabolism, such as hyperglycemia, an increased level of total lipids, cholesterol and its fractions, beta-lipoproteids, a fall of ILA in the blood serum, as well as variations in the morphological picture of the aortic wall. The above findings suggest that a protracted administration of glucose can produce both diabetogenic and atherogenic effects.", "contents": "[Diabetogenic and atherogenic effects of glucose]. Tests were set up on 59 albino male-rats with reproduced functional overstress and depletion of the insular system of the pancreas thorough a long-term (for 50, 100 days) peroral introduction of glucose (2 g/100 g body weight, every other day) and with and alloxan-induced diabetes (achieved by poisoning the animals with a 2.5% alloxan solution, 15 mg/100 g administered in a single dose intraperitoneally). A comparison of the data obtained ascertained the presence of a number of similar pathobiochemical changes in the metabolism, viz. hyperglycemia, an increase of the free cholesterol fraction, a diminution of the bound cholesterol fraction and a fall of the insulin-like activity (ILA) in the blood serum, a rise in glycogen and beta-lipoproteids in the liver; morphologically--a reduced count of Langerhan's islands beta-cells, less intensive colouration of the specific granulation in their cytoplasma manifestations of vacuolar and granular dystrophy of the liver. Further tests were staged on 23 rabbits involving a long-term introduction of glucose (in amounts of 25 g/kg every other day) and a cholesterol-induced atherosclerosis (by administering 0.2 g/kg of cholesterol in oil, daily), which also showed similar changes in the figures of the carbohydrate and fat-lipoids metabolism, such as hyperglycemia, an increased level of total lipids, cholesterol and its fractions, beta-lipoproteids, a fall of ILA in the blood serum, as well as variations in the morphological picture of the aortic wall. The above findings suggest that a protracted administration of glucose can produce both diabetogenic and atherogenic effects."} {"id": "PMID:173089", "title": "[Level of nicotinic acid and NAD in the organs of rats during complete starvation].", "content": "In the liver, heart, brain and pancreas of control rats and of test animals fasting for 2, 4, 7 and 11 days the content of nicotinic acid in the organs was determined by the microbiological method and that of NAD- biochemically. After 2, 7 and 11 days of fasting a statistically significant increase in the level of nicotinic acid per 1 g of tissue was ascertained in all the organs. After 4 days of fasting an increase in the vitamin content proved insignificant. With the calculation covering the entire organ the fall of the PP level in the liver proceeded uniformly and after the 11th day of fasting it amounted to 46 per cent, whereas in the heart the decline was insignificant, the content of the vitamin in the brain, however, rose by 21 per cent. The NAD level in the organs, calculated to 1 g of the tissue, changed but little and with the estimates covering the whole of the organ there could be noted its substantial drop in the liver, especially after 11 days of fasting (by as much as 62 per cent), and to a lesser degree--in the heart and pancreas and rise in the brain (by 13 per cent).", "contents": "[Level of nicotinic acid and NAD in the organs of rats during complete starvation]. In the liver, heart, brain and pancreas of control rats and of test animals fasting for 2, 4, 7 and 11 days the content of nicotinic acid in the organs was determined by the microbiological method and that of NAD- biochemically. After 2, 7 and 11 days of fasting a statistically significant increase in the level of nicotinic acid per 1 g of tissue was ascertained in all the organs. After 4 days of fasting an increase in the vitamin content proved insignificant. With the calculation covering the entire organ the fall of the PP level in the liver proceeded uniformly and after the 11th day of fasting it amounted to 46 per cent, whereas in the heart the decline was insignificant, the content of the vitamin in the brain, however, rose by 21 per cent. The NAD level in the organs, calculated to 1 g of the tissue, changed but little and with the estimates covering the whole of the organ there could be noted its substantial drop in the liver, especially after 11 days of fasting (by as much as 62 per cent), and to a lesser degree--in the heart and pancreas and rise in the brain (by 13 per cent)."} {"id": "PMID:173101", "title": "[The intestinal parasite fauna in patients, returned from the tropics, from the Dresden district].", "content": "It is reported on the affection with intestinal parasites in 438 persons who returned from the tropics. In these test persons were also established only those species of parasites which were proved in the Dresden inhabitants. However, there were remarkable quantitative differences between the affection of the persons returning from the tropics and the Dresden inhabitants. Thus by laboratory examinations in Dresden in the persons returning from the tropics were established infections with Entamoeba histolytica (7.0%), with Dientamoeba fragilis (17.9%), with Lamblia intestinalis (9.0%) as well as with Trichuris trichiura (3.4%), where as the extensity of affection with the corresponding parasites is for the Dresden inhabitants 1.9%, 4.7%, 5.0%, and 1.6%. It is referred to the fact that all persons who returned from the tropics should parasitologically be examined for an infection with Entamoeba histolytica.", "contents": "[The intestinal parasite fauna in patients, returned from the tropics, from the Dresden district]. It is reported on the affection with intestinal parasites in 438 persons who returned from the tropics. In these test persons were also established only those species of parasites which were proved in the Dresden inhabitants. However, there were remarkable quantitative differences between the affection of the persons returning from the tropics and the Dresden inhabitants. Thus by laboratory examinations in Dresden in the persons returning from the tropics were established infections with Entamoeba histolytica (7.0%), with Dientamoeba fragilis (17.9%), with Lamblia intestinalis (9.0%) as well as with Trichuris trichiura (3.4%), where as the extensity of affection with the corresponding parasites is for the Dresden inhabitants 1.9%, 4.7%, 5.0%, and 1.6%. It is referred to the fact that all persons who returned from the tropics should parasitologically be examined for an infection with Entamoeba histolytica."} {"id": "PMID:173103", "title": "Microfilaments in human epithelial cancer cells.", "content": "The occurence, distribution, and ultrastructural morphology of microfilaments in malignant epithelial cells of invasive squamous cell carcinoma of human oral cavity were studied by electron microscopy. The findings are compared with those in malignant oral epithelial cells of carcinoma-in-situ. In the malignant cells of invasive carcinoma, microfilaments 50-70 A in diameter are prominent in the cortical cytoplasm of the lateral and basal cell surfaces, adjacent and parallel to the plasma membrane, and extending into cell processes and microvillous extensions. Additional microfilaments are found to run from the peripheral cytoplasm to the perinuclear region. The microfilaments are aggregated into bundles aligned parallel to the long axis of the cell and display foci of increased electron density. They also tend to be aggregated into complex polygonal arrays. These microfilaments are similar in organization, concentration and ultrastructural architecture to those of various other nonmuscle cells, where they are thought to be capable of contraction and associated with cell motility. The presence of a microfilament system believed to be associated with contractile and motile cell processes may be an important characteristic of malignant cells of invasive tumors. The lack of abundant organized microfilaments in malignant cells in the absence of tumor invasion, and the presence of a prominent microfilament system in cells of invasive tumors, suggest that the microfilaments are related to the invasive properties of malignant tumor cells.", "contents": "Microfilaments in human epithelial cancer cells. The occurence, distribution, and ultrastructural morphology of microfilaments in malignant epithelial cells of invasive squamous cell carcinoma of human oral cavity were studied by electron microscopy. The findings are compared with those in malignant oral epithelial cells of carcinoma-in-situ. In the malignant cells of invasive carcinoma, microfilaments 50-70 A in diameter are prominent in the cortical cytoplasm of the lateral and basal cell surfaces, adjacent and parallel to the plasma membrane, and extending into cell processes and microvillous extensions. Additional microfilaments are found to run from the peripheral cytoplasm to the perinuclear region. The microfilaments are aggregated into bundles aligned parallel to the long axis of the cell and display foci of increased electron density. They also tend to be aggregated into complex polygonal arrays. These microfilaments are similar in organization, concentration and ultrastructural architecture to those of various other nonmuscle cells, where they are thought to be capable of contraction and associated with cell motility. The presence of a microfilament system believed to be associated with contractile and motile cell processes may be an important characteristic of malignant cells of invasive tumors. The lack of abundant organized microfilaments in malignant cells in the absence of tumor invasion, and the presence of a prominent microfilament system in cells of invasive tumors, suggest that the microfilaments are related to the invasive properties of malignant tumor cells."} {"id": "PMID:173104", "title": "[Comparative studies of simultaneous intraoperative frozen sections and imprint cytology of the mamma (author's transl)].", "content": "250 tissue biopsies of the mamma were examined simultaneously by intraoperative histology (frozen sections) and imprint cytology. In 95% of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, sclerosing adenosis and carcinomas and the significance of the imprint cytology for the diagnosis of difficult cases was pointed out in detail. The results have demonstrated, that such a cytologic examination can not be a substitute for intraoperative frozen sections - but the simultaneous cytologic examination of unfixed mamma biopsies can be a good searching method and can be helpful in the intraoperative diagnostic.", "contents": "[Comparative studies of simultaneous intraoperative frozen sections and imprint cytology of the mamma (author's transl)]. 250 tissue biopsies of the mamma were examined simultaneously by intraoperative histology (frozen sections) and imprint cytology. In 95% of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, sclerosing adenosis and carcinomas and the significance of the imprint cytology for the diagnosis of difficult cases was pointed out in detail. The results have demonstrated, that such a cytologic examination can not be a substitute for intraoperative frozen sections - but the simultaneous cytologic examination of unfixed mamma biopsies can be a good searching method and can be helpful in the intraoperative diagnostic."} {"id": "PMID:173105", "title": "[Nucleotide alterations of 18 S and 28 S ribosomal RNA from rat liver during carcinogenesis induced by N-nitrosomorpholine (author's transl)].", "content": "After administration of N-nitrosomorpholine (NNM) to female Wistar-rats the ribosomal RNA (18 S and 28S rRNA) of the livers contained \"abnormal\" dinucleotides which were resistant against treatment with alkali or with spleen phosphodiesterase. These and further observations are discussed in view of the hypothesis that during the induction of liver tumors a metabolite of NNM causes crosslinks of nucleic acid bases. The application of this hypothesis on the effects of NNM upon DNA permits to explain the additional results that have been obtained. Observations on NNM metabolism as reported in the literature are not inconsistent with this interpretation.", "contents": "[Nucleotide alterations of 18 S and 28 S ribosomal RNA from rat liver during carcinogenesis induced by N-nitrosomorpholine (author's transl)]. After administration of N-nitrosomorpholine (NNM) to female Wistar-rats the ribosomal RNA (18 S and 28S rRNA) of the livers contained \"abnormal\" dinucleotides which were resistant against treatment with alkali or with spleen phosphodiesterase. These and further observations are discussed in view of the hypothesis that during the induction of liver tumors a metabolite of NNM causes crosslinks of nucleic acid bases. The application of this hypothesis on the effects of NNM upon DNA permits to explain the additional results that have been obtained. Observations on NNM metabolism as reported in the literature are not inconsistent with this interpretation."} {"id": "PMID:173106", "title": "Spermatogenesis in free living mite, Pergamasus viator Hala\u015d (Parasitidae, Mesostigmata). I. Fine structure of spermatozoa.", "content": "The spermatozoa of Pergamasus viator Hala\u015d. from Parasitidae family (Acarina, Mesostigmata) were studied in light and electron microscopy. The spermatozoa are motionless (in vitro) rod-shaped cells 110 mum long, in which six morphologically different zones can be distinguished: acrosomal zone, mitochondrial zone, zone of granular bodies, zone of striated bodies, nuclear zone and retronuclear zone. The acrosomal zone filled with the granular subacrosomal material contains at the top the acrosomal vesicle. Plasmalemma forms 19--21 folds running longitudinally along the spermatozoon. Within each fold there is a flattened canaliculus, and under each fold is found a stoff band. Between the stiff bands flattened cisternae are observed. Apart from the above structures the spermatozoon contains: the nucleus, striated bodies, granular bodies and mitochondria. The flagella-like structures or centrioles were not found. A possible origin and role of the structures decribed in spermatozoa of P. viator are discussed.", "contents": "Spermatogenesis in free living mite, Pergamasus viator Hala\u015d (Parasitidae, Mesostigmata). I. Fine structure of spermatozoa. The spermatozoa of Pergamasus viator Hala\u015d. from Parasitidae family (Acarina, Mesostigmata) were studied in light and electron microscopy. The spermatozoa are motionless (in vitro) rod-shaped cells 110 mum long, in which six morphologically different zones can be distinguished: acrosomal zone, mitochondrial zone, zone of granular bodies, zone of striated bodies, nuclear zone and retronuclear zone. The acrosomal zone filled with the granular subacrosomal material contains at the top the acrosomal vesicle. Plasmalemma forms 19--21 folds running longitudinally along the spermatozoon. Within each fold there is a flattened canaliculus, and under each fold is found a stoff band. Between the stiff bands flattened cisternae are observed. Apart from the above structures the spermatozoon contains: the nucleus, striated bodies, granular bodies and mitochondria. The flagella-like structures or centrioles were not found. A possible origin and role of the structures decribed in spermatozoa of P. viator are discussed."} {"id": "PMID:173109", "title": "Adenyl cyclase activity in lymphocytes stimulated with immunologically specific and nonspecific stimuli.", "content": "Adenyl cyclase activity was determined in suspensions of rat lymphocytes from animals with postadjuvant polyarthritis and from healthy animals. Adrenaline was used as activator of the enzyme. Adenyl cyclase activity was determined by the method based on synthesis of 3H-cAMP from 3H-ATP in intact cells. The influence of imidazole on blastic transformation of lymphocytes sensitized in the process of postadjuvant polyarthritis and subjected to the action of antigen, i.e. Old Tuberculin, was also studied. The response of sensitized lymphocytes to antigen in the presence of a nonspecific stimulus, adrenaline, was also investigated. In addition, the action of adrenaline on incorporation of 3H-thymidine in cultures of nonsensitized lymphocytes was observed. Adenyl cyclase activity in suspensions of lymphocytes from animals with postadjuvant polyarthritis was higher than in suspensions of lymphocytes from healthy animals. Following administration of adrenaline as activator of the enzyme, lymphocytes from healthy animals showed higher activity of the enzyme than lymphocytes from the sick rats. Imidazole inhibited the response of lymphocytes sensitized to antigen. Adrenaline had no influence on blastic transformation of lymphocytes sensitized to antigen. Adrenaline slightly inhibited incorporation of H-thymidine in cultures of sensitized lymphocytes in absence of antigen in cultures of nonsensitized lymphocytes.", "contents": "Adenyl cyclase activity in lymphocytes stimulated with immunologically specific and nonspecific stimuli. Adenyl cyclase activity was determined in suspensions of rat lymphocytes from animals with postadjuvant polyarthritis and from healthy animals. Adrenaline was used as activator of the enzyme. Adenyl cyclase activity was determined by the method based on synthesis of 3H-cAMP from 3H-ATP in intact cells. The influence of imidazole on blastic transformation of lymphocytes sensitized in the process of postadjuvant polyarthritis and subjected to the action of antigen, i.e. Old Tuberculin, was also studied. The response of sensitized lymphocytes to antigen in the presence of a nonspecific stimulus, adrenaline, was also investigated. In addition, the action of adrenaline on incorporation of 3H-thymidine in cultures of nonsensitized lymphocytes was observed. Adenyl cyclase activity in suspensions of lymphocytes from animals with postadjuvant polyarthritis was higher than in suspensions of lymphocytes from healthy animals. Following administration of adrenaline as activator of the enzyme, lymphocytes from healthy animals showed higher activity of the enzyme than lymphocytes from the sick rats. Imidazole inhibited the response of lymphocytes sensitized to antigen. Adrenaline had no influence on blastic transformation of lymphocytes sensitized to antigen. Adrenaline slightly inhibited incorporation of H-thymidine in cultures of sensitized lymphocytes in absence of antigen in cultures of nonsensitized lymphocytes."} {"id": "PMID:173108", "title": "[Disorders in conditioned reflex activity and morphologic changes in the brains of rats deprived of paradoxical sleep].", "content": "Reproduction of defensive conditioned reflexes elaborated before a 96-hour deprivation of paradoxal sleep (DPS) in rats was sharply disturbed immediately after DPS, but became normal 24 hours later. Elaboration of conditioned reflexes immediately after DPS is followed by a disturbance of their reproduction, while such elaboration 24 hours after DPS does not affect their subsequent reproduction. It is assumed that dissociated learning plays an important part in the origin of the disclosed disturbances of conditioned activity. Morphological investigation of the animals' brain immediately after DPS revealed activation of neuroglia with productive-dystrophic changes of astrocytes, an increase in the sizes of nuclei of neurones in the motor cortex and hippocampus, and pronounced vascular changes. A day after DPS the changes of the astrocyte glia and the vessels are less pronounced, and the sizes of neurone nuclei in the motor cortex diminish.", "contents": "[Disorders in conditioned reflex activity and morphologic changes in the brains of rats deprived of paradoxical sleep]. Reproduction of defensive conditioned reflexes elaborated before a 96-hour deprivation of paradoxal sleep (DPS) in rats was sharply disturbed immediately after DPS, but became normal 24 hours later. Elaboration of conditioned reflexes immediately after DPS is followed by a disturbance of their reproduction, while such elaboration 24 hours after DPS does not affect their subsequent reproduction. It is assumed that dissociated learning plays an important part in the origin of the disclosed disturbances of conditioned activity. Morphological investigation of the animals' brain immediately after DPS revealed activation of neuroglia with productive-dystrophic changes of astrocytes, an increase in the sizes of nuclei of neurones in the motor cortex and hippocampus, and pronounced vascular changes. A day after DPS the changes of the astrocyte glia and the vessels are less pronounced, and the sizes of neurone nuclei in the motor cortex diminish."} {"id": "PMID:173112", "title": "[Duration of possible detection of cysts of Entamoeba histolytica in stool samples (author's transl)].", "content": "Stool samples containing large numbers of cysts of Entamoeba histolytica were stored at room temperature (+22 degrees C - +25 degrees C) and at +4 degrees C respectively. After 1 h, 6 h, 12 h, 20 h, 36 h, 5 d, 7 d, 10 d, 15 d, 20 d, and 30 d smears were performed and stained according to the method of HEIDENHAIN. In both groups cysts remained easily detectable for about one week; after that time, however, distinct changes of the morphology of the cysts occurred and the number of detectable individuals decreased rapidly. After 30 days storage of the stool cysts could be recognized only exceptionally and only in samples stored at 4 degrees C. At that time the microscopic picture of the smears had undergone heavy changes; yeasts predominated over bacteria. In addition it was shown, that freezing of stoll samples (at - 20 degrees C and -80 degrees C) destroyed practically all cysts.", "contents": "[Duration of possible detection of cysts of Entamoeba histolytica in stool samples (author's transl)]. Stool samples containing large numbers of cysts of Entamoeba histolytica were stored at room temperature (+22 degrees C - +25 degrees C) and at +4 degrees C respectively. After 1 h, 6 h, 12 h, 20 h, 36 h, 5 d, 7 d, 10 d, 15 d, 20 d, and 30 d smears were performed and stained according to the method of HEIDENHAIN. In both groups cysts remained easily detectable for about one week; after that time, however, distinct changes of the morphology of the cysts occurred and the number of detectable individuals decreased rapidly. After 30 days storage of the stool cysts could be recognized only exceptionally and only in samples stored at 4 degrees C. At that time the microscopic picture of the smears had undergone heavy changes; yeasts predominated over bacteria. In addition it was shown, that freezing of stoll samples (at - 20 degrees C and -80 degrees C) destroyed practically all cysts."} {"id": "PMID:173113", "title": "Phenotypic chain formation in Clostridium welchii by suramin.", "content": "Cl. welchii NCTC 6785 was grown in 1% glucose containing medium having 1% Suramin w/v. The cells grew into long chains of thirty units. This effect was not found beyond 0.5% concentration. On transfer into Suramin free medium the chains reverted to normal morphology indicating the change in morphology to be phenotypic.", "contents": "Phenotypic chain formation in Clostridium welchii by suramin. Cl. welchii NCTC 6785 was grown in 1% glucose containing medium having 1% Suramin w/v. The cells grew into long chains of thirty units. This effect was not found beyond 0.5% concentration. On transfer into Suramin free medium the chains reverted to normal morphology indicating the change in morphology to be phenotypic."} {"id": "PMID:173119", "title": "[Study of the interrelationship between the content of immunizing units and the immunogenicity of C1. perfringens anatoxins].", "content": "Comparative experiments were conducted on rabbits and guinea pigs; a study was made of the immunological efficacy of the toxoids with a different content of the immunizing units (IU/ml). There was revealed a regular quantitative interrelationship between the content of the IU/ml in the toxoids, the level of the antitoxin formation and the extent of protection against the experimental gas gangrene in the immunized animals.", "contents": "[Study of the interrelationship between the content of immunizing units and the immunogenicity of C1. perfringens anatoxins]. Comparative experiments were conducted on rabbits and guinea pigs; a study was made of the immunological efficacy of the toxoids with a different content of the immunizing units (IU/ml). There was revealed a regular quantitative interrelationship between the content of the IU/ml in the toxoids, the level of the antitoxin formation and the extent of protection against the experimental gas gangrene in the immunized animals."} {"id": "PMID:173120", "title": "[Comparative characteristics of the toxic properties of the whooping cough microbes].", "content": "The author presents materials concerning the study of the toxic properties of 12 pertussis cultures used in the USSR for the production of vaccines. As a result of studying the toxic properties of the microbes in the test of the change of the weight of mice, and in experiments of testing the anaphylactogenic and histamine-sensitizing activities it was revealed that the strains of pertussis microbes differed by the quantitative content in them of the thermolabile toxin, endotoxin, lymphocytosis-stimulating and histamine-sensitizing factors; therefore, the period of keeping the pertussis suspensions for 1.5 months from the moment of detoxication proved to be inadequate for some of the strains. Since the toxic properties of the strains failed to correlate with their protective activity, in recommendation of pertussis strains for the production of pertussis vaccine preference should be given to the strains with lesser toxic properties.", "contents": "[Comparative characteristics of the toxic properties of the whooping cough microbes]. The author presents materials concerning the study of the toxic properties of 12 pertussis cultures used in the USSR for the production of vaccines. As a result of studying the toxic properties of the microbes in the test of the change of the weight of mice, and in experiments of testing the anaphylactogenic and histamine-sensitizing activities it was revealed that the strains of pertussis microbes differed by the quantitative content in them of the thermolabile toxin, endotoxin, lymphocytosis-stimulating and histamine-sensitizing factors; therefore, the period of keeping the pertussis suspensions for 1.5 months from the moment of detoxication proved to be inadequate for some of the strains. Since the toxic properties of the strains failed to correlate with their protective activity, in recommendation of pertussis strains for the production of pertussis vaccine preference should be given to the strains with lesser toxic properties."} {"id": "PMID:173121", "title": "[Effect of a chronic iodine deficit in the ration on the development of the infectious process].", "content": "It was revealed that the infectious process in albino rats kept for 4-5 months on an iodine-deficiency diet was characterised by a tendency to dissemination. The seeding efficiency from the parenchymatous organs increased in such animals significantly, whereas the bactericidal properties of the plasma and the phagocytic activity of blood neutrophils decreased; this was apparently associated with depression of the intracellular metabolism reflected in reduction of the cytochromoxidase and peroxidase in the neutrophils.", "contents": "[Effect of a chronic iodine deficit in the ration on the development of the infectious process]. It was revealed that the infectious process in albino rats kept for 4-5 months on an iodine-deficiency diet was characterised by a tendency to dissemination. The seeding efficiency from the parenchymatous organs increased in such animals significantly, whereas the bactericidal properties of the plasma and the phagocytic activity of blood neutrophils decreased; this was apparently associated with depression of the intracellular metabolism reflected in reduction of the cytochromoxidase and peroxidase in the neutrophils."} {"id": "PMID:173122", "title": "[Modelling of biological encoding mechanisms as a system with distributed parameters].", "content": "The encoder region in receptors and neurons is represented by the inhomogeneous origin of the axon. The axon diameter and the excitability are in fact space-dependent. For the analysis the soma is described by a system with concentrated parameters followed by an inhomogeneous axon. The membrane properties are approximated by the slightly modified Hodgkin-Huxley equations. The assumption that the space-dependence of the excitability originates in variations of the conductance value for sodium ions accounts for a number of experimental results. The influence of other membrane parameters upon the mechanism of impulse generation and transmission has also been analysed.", "contents": "[Modelling of biological encoding mechanisms as a system with distributed parameters]. The encoder region in receptors and neurons is represented by the inhomogeneous origin of the axon. The axon diameter and the excitability are in fact space-dependent. For the analysis the soma is described by a system with concentrated parameters followed by an inhomogeneous axon. The membrane properties are approximated by the slightly modified Hodgkin-Huxley equations. The assumption that the space-dependence of the excitability originates in variations of the conductance value for sodium ions accounts for a number of experimental results. The influence of other membrane parameters upon the mechanism of impulse generation and transmission has also been analysed."} {"id": "PMID:173123", "title": "LP-X in cholestasis.", "content": "Extrahepatic and intrahepatic biliary obstruction of different etiology were studied in 62 patients, who were investigated for the presence of lipoprotein X (Lp-X). It was found present in 19 of 20 cholestasis by lithiasis, in all three primary biliary cirrhosis patients, in 2 of 4 cirrhosis, in 5 of 13 hepatitis, in all three benign recurrent intrahepatic cholestasis and in 1 of 2 recurrent juandice of pregnancy. It was found in a Dubin Johnson. Lp-X disappeared in 4 patients within two weeks after relief of the obstruction. It was found in patients with cholestatic hepatitis during the first week of jaundice. It was found in the first 48 hours in three patients with cholestasis by lithiasis. Lp-X does not help in differential diagnosis between extrahepatic and intrahepatic biliary obstruction, but the time of its appearance could contribute to it in some cases. A word of caution is raised in indicating surgery in a cholestatic patient without the presence of Lp-X.", "contents": "LP-X in cholestasis. Extrahepatic and intrahepatic biliary obstruction of different etiology were studied in 62 patients, who were investigated for the presence of lipoprotein X (Lp-X). It was found present in 19 of 20 cholestasis by lithiasis, in all three primary biliary cirrhosis patients, in 2 of 4 cirrhosis, in 5 of 13 hepatitis, in all three benign recurrent intrahepatic cholestasis and in 1 of 2 recurrent juandice of pregnancy. It was found in a Dubin Johnson. Lp-X disappeared in 4 patients within two weeks after relief of the obstruction. It was found in patients with cholestatic hepatitis during the first week of jaundice. It was found in the first 48 hours in three patients with cholestasis by lithiasis. Lp-X does not help in differential diagnosis between extrahepatic and intrahepatic biliary obstruction, but the time of its appearance could contribute to it in some cases. A word of caution is raised in indicating surgery in a cholestatic patient without the presence of Lp-X."} {"id": "PMID:173124", "title": "Immune responses to treatment with natural and synthetic ACTH in bronchial asthma.", "content": "Two comparable groups of asthmatics each with 10 patients were treated during 2 years at scheduled intervals with either natural or synthetic ACTH up to a total dose of 2000-95-- IU. All patients had previously been given the natural but never the synthetic hormone. Intradermal tests with natural and synthetic ACTH were performed before treatment and after 1, 12 and 24 months. Serum samples were also taken on these occasions and analysed for antibodies against ACTH, vasopressin and porcine gamma-globulin. No sign of clinical allergy to ACTH was noted in any of the patients during the 2-year period. The incidence of intradermal reactions against natural ACTH was high at the onset of treatment but was not increased by treatment with either synthetic or natural ACTH, while the reactivity rate against synthetic ACTH was increased after both types of treatment. The incidence of IgE reactions against synthetic ACTH at the 20 U/ml level was significantly increased after 12 months' treatment with either natural or synthetic hormone. A high incidence of low-titered agglutinating antibodies against natural or synthetic ACTH was demonstrated before treatment in both the groups, but no significant change in incidence or mean titre against natural or synthetic ACTH or porcine gamma-globulin was noted during treatment with the natural or the synthetic preparation. A few patients, however, did display an increased agglutinating titre against ACTH after 12 months' treatment. Rather unexpectedly, most sera reacting with ACTH were found to react also with vasopressin and a significant increase of the incidence of these reactions and of the titres occurred during the treatment with synthetic as well as with natural ACTH. Two cases have been examined in detail, one because of a fulminant shock after synthetic ACTH and the other because of very high antibody titres without clinical symptoms of ACTH allergy.", "contents": "Immune responses to treatment with natural and synthetic ACTH in bronchial asthma. Two comparable groups of asthmatics each with 10 patients were treated during 2 years at scheduled intervals with either natural or synthetic ACTH up to a total dose of 2000-95-- IU. All patients had previously been given the natural but never the synthetic hormone. Intradermal tests with natural and synthetic ACTH were performed before treatment and after 1, 12 and 24 months. Serum samples were also taken on these occasions and analysed for antibodies against ACTH, vasopressin and porcine gamma-globulin. No sign of clinical allergy to ACTH was noted in any of the patients during the 2-year period. The incidence of intradermal reactions against natural ACTH was high at the onset of treatment but was not increased by treatment with either synthetic or natural ACTH, while the reactivity rate against synthetic ACTH was increased after both types of treatment. The incidence of IgE reactions against synthetic ACTH at the 20 U/ml level was significantly increased after 12 months' treatment with either natural or synthetic hormone. A high incidence of low-titered agglutinating antibodies against natural or synthetic ACTH was demonstrated before treatment in both the groups, but no significant change in incidence or mean titre against natural or synthetic ACTH or porcine gamma-globulin was noted during treatment with the natural or the synthetic preparation. A few patients, however, did display an increased agglutinating titre against ACTH after 12 months' treatment. Rather unexpectedly, most sera reacting with ACTH were found to react also with vasopressin and a significant increase of the incidence of these reactions and of the titres occurred during the treatment with synthetic as well as with natural ACTH. Two cases have been examined in detail, one because of a fulminant shock after synthetic ACTH and the other because of very high antibody titres without clinical symptoms of ACTH allergy."} {"id": "PMID:173126", "title": "Pathology of the human spinal ganglia in varicella-zoster virus infection.", "content": "Spinal ganglia from a patient who died on the 6th day of varicella infection were examined by immunofluorescence and electron microscopy, and were compared with spinal ganglia from a patient dying on the 17th day of herpes zoster infection. In herpes zoster, typical intranuclear inclusion bodies were found in neurons, satellite cells and fibroblast-like cells of the ganglia, which contained numerous naked virus particles. In varicella, few changes were found by light microscopy but viral antigen was detected in a few neurons and satellite cells by immunofluorescence. Electron microscopy revealed scattered virus particles near the nuclear membrane of a neuron, satellite cells and capsular cells and enveloped particles in the cytoplasm of satellite cells. The particles in the nuclei were mostly naked virions with specific crescent-like inner-nuclear structure; those in the cytoplasm had complete and incomplete envelopes and showed pleomorphism. A \"virus-like\" intranuclear filament found in mononuclear cells in herpes zoster and a \"plexiform vermicellar array\" found in the nuclei of neurons in varicella are at present considered to be non-specific nuclear changes caused probably by viral infections.", "contents": "Pathology of the human spinal ganglia in varicella-zoster virus infection. Spinal ganglia from a patient who died on the 6th day of varicella infection were examined by immunofluorescence and electron microscopy, and were compared with spinal ganglia from a patient dying on the 17th day of herpes zoster infection. In herpes zoster, typical intranuclear inclusion bodies were found in neurons, satellite cells and fibroblast-like cells of the ganglia, which contained numerous naked virus particles. In varicella, few changes were found by light microscopy but viral antigen was detected in a few neurons and satellite cells by immunofluorescence. Electron microscopy revealed scattered virus particles near the nuclear membrane of a neuron, satellite cells and capsular cells and enveloped particles in the cytoplasm of satellite cells. The particles in the nuclei were mostly naked virions with specific crescent-like inner-nuclear structure; those in the cytoplasm had complete and incomplete envelopes and showed pleomorphism. A \"virus-like\" intranuclear filament found in mononuclear cells in herpes zoster and a \"plexiform vermicellar array\" found in the nuclei of neurons in varicella are at present considered to be non-specific nuclear changes caused probably by viral infections."} {"id": "PMID:173127", "title": "Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma.", "content": "A biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 A thick filaments. Classical Rosenthal fibers were also identified. In addition many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels.", "contents": "Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma. A biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 A thick filaments. Classical Rosenthal fibers were also identified. In addition many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels."} {"id": "PMID:173128", "title": "Double encephalitis with herpes simplex virus and cytomegalovirus in an adult.", "content": "A 51-year-old housewife developed symptoms of a cold followed by high fever, delirium, coma, rigidity of extremity muscles, positive Babinski sign and generalized convulsions, while complement-fixing antibody titre to herpes simplex virus in the sera raised over 128 X and declined to 8 X in the course. She finally expired of bronchopneumonia following status epilepticus after 94 days of illness. Severe necrosis with extensive hemorrhage in the white matter was predominant in the temporal, insular and orbitofrontal cortex, thalamus and globus pallidus. Focal rarefaction of the cerebral cortex with a very few eosinophilic intranuclear inclusions in the oligodendroglia and nerve cells, nerve cell destruction in the substantia nigra with glial nodules and perivascular inflammatory cell cuffs were observed. Abundant cytomegalic inclusion cells, originating from hypertrophic astrocytes, were present in the necrotic areas of cerebrum as well as in the rarefied tissue in the subependymal layers of the brainstem and cerebellum. Electron-microscopic study of the cytomegalic cells demonstrated the presence of numerous virions in both nucleus and cytoplasm. Fortuitour infection of the brain by cytomegalovirus with necrotizing encephalitis by herpes simplex virus is unique. The cause of double viral infections and severe lesions by less virulent strains is discussed.", "contents": "Double encephalitis with herpes simplex virus and cytomegalovirus in an adult. A 51-year-old housewife developed symptoms of a cold followed by high fever, delirium, coma, rigidity of extremity muscles, positive Babinski sign and generalized convulsions, while complement-fixing antibody titre to herpes simplex virus in the sera raised over 128 X and declined to 8 X in the course. She finally expired of bronchopneumonia following status epilepticus after 94 days of illness. Severe necrosis with extensive hemorrhage in the white matter was predominant in the temporal, insular and orbitofrontal cortex, thalamus and globus pallidus. Focal rarefaction of the cerebral cortex with a very few eosinophilic intranuclear inclusions in the oligodendroglia and nerve cells, nerve cell destruction in the substantia nigra with glial nodules and perivascular inflammatory cell cuffs were observed. Abundant cytomegalic inclusion cells, originating from hypertrophic astrocytes, were present in the necrotic areas of cerebrum as well as in the rarefied tissue in the subependymal layers of the brainstem and cerebellum. Electron-microscopic study of the cytomegalic cells demonstrated the presence of numerous virions in both nucleus and cytoplasm. Fortuitour infection of the brain by cytomegalovirus with necrotizing encephalitis by herpes simplex virus is unique. The cause of double viral infections and severe lesions by less virulent strains is discussed."} {"id": "PMID:173129", "title": "Electron microscopic investigation of inclusion material in a case of adult metachromatic leukodystrophy; observations on kidney biopsy, peripheral nerve and cerebral white matter.", "content": "The fine structural characteristics of storage products in peripheral nerve, kidney and cerebral white matter, from a case of adult metachromatic leukodystrophy are described. There were pronounced differences from the fine structural aspects in late infantile cases. A large proportion of the inclusions did not exhibit a unit membrane. An hypothesis is proposed to clarify the delayed manifestation of this type of metachromatic leukodystrophy until childhood.", "contents": "Electron microscopic investigation of inclusion material in a case of adult metachromatic leukodystrophy; observations on kidney biopsy, peripheral nerve and cerebral white matter. The fine structural characteristics of storage products in peripheral nerve, kidney and cerebral white matter, from a case of adult metachromatic leukodystrophy are described. There were pronounced differences from the fine structural aspects in late infantile cases. A large proportion of the inclusions did not exhibit a unit membrane. An hypothesis is proposed to clarify the delayed manifestation of this type of metachromatic leukodystrophy until childhood."} {"id": "PMID:173130", "title": "Quantitative analysis of radioisotopic angiography in trophoblastic neoplasia.", "content": "The diagnostic significance of radioisotopic angiography in the clinical management of trophoblastic neoplasia was studied by analyzing the patterns of radioisotope (RI)-dynamic curve obtained by processing sequential image with a computer, and an attempt was made to express numerically the size of tumors present in vivo. It was demonstrated that the total activities of RI in the abnormal phase of RI-dynamic curves in trophoblastic neoplasia were closely correlated with the sizes of the intrauterine tumors actually resected.", "contents": "Quantitative analysis of radioisotopic angiography in trophoblastic neoplasia. The diagnostic significance of radioisotopic angiography in the clinical management of trophoblastic neoplasia was studied by analyzing the patterns of radioisotope (RI)-dynamic curve obtained by processing sequential image with a computer, and an attempt was made to express numerically the size of tumors present in vivo. It was demonstrated that the total activities of RI in the abnormal phase of RI-dynamic curves in trophoblastic neoplasia were closely correlated with the sizes of the intrauterine tumors actually resected."} {"id": "PMID:173125", "title": "A case of multiple sclerosis associated with defective neuromuscular transmission.", "content": "A 38-year-old woman developed relapsing disseminated sclerosis associated with myasthenic syndrome. The cerebrospinal fluid showed 12 lymphocytes per 1 mul and paretic colloidal curve. The serum contained antibody against smooth muscle antigen (titre 1 : 10) but no antibody against nuclear antigen or VDRL antigen. Repetitive stimulation of the right ulnar nerve at 35 c/sec. demonstrated typical decrements between 70 and 72%. The prostigmine test showed significant diminishing of decrements. The possible immunopathological mechanism of myasthenic syndrome in multiple sclerosis was briefly discussed.", "contents": "A case of multiple sclerosis associated with defective neuromuscular transmission. A 38-year-old woman developed relapsing disseminated sclerosis associated with myasthenic syndrome. The cerebrospinal fluid showed 12 lymphocytes per 1 mul and paretic colloidal curve. The serum contained antibody against smooth muscle antigen (titre 1 : 10) but no antibody against nuclear antigen or VDRL antigen. Repetitive stimulation of the right ulnar nerve at 35 c/sec. demonstrated typical decrements between 70 and 72%. The prostigmine test showed significant diminishing of decrements. The possible immunopathological mechanism of myasthenic syndrome in multiple sclerosis was briefly discussed."} {"id": "PMID:173131", "title": "Antibodies to herpesvirus hominis types 1 and 2 among women with neoplastic change of uterine cervix.", "content": "The occurrence of antibodies to herpesvirus hominis types 1 and 2 was studied in Finland among patients with a neoplastic change of the uterine cervix. The following groups were studied: 220 patients with malignant or premalignant lesions of the uterine cervix, 143 control patients matched for age, socioeconomic level, marital status, home district and number of deliveries and 82 patients with breast or stomach cancer. Antibodies to HVH types 1 and 2 were determined using the neutralization test. Sera showing an index of less than or equal to 100 were accepted as positive to type 1 and those of greater than or equal to 85 as positive to type 2. Among patients with a neoplastic change of the uterine cervix the frequency of type 1 antibodies varied between 70% and 79%. In the control group the frequency was 84% and among patients with some other malignancy 91%. These differences in the frequencies of type 1 antibody were not statistically significant. Type 2 antibodies were present in 35 to 47% among dysplasia and malignancy of the cervix. In the control group it was 18% and in other malignancies 20%. The differences between these groups and the controls were almost significant, significant and highly significant, respectively. Differences could also be observed in the distribution of neutralization indexes. The average index calculated from all sera was 48 both in the control group and in the group of other malignancies, while in sera of patients with dysplasia, carcinoma in situ and invasive carcinoma the respective vlaues were 70, 66 and 79. The results are discussed in terms of the role of herpesvirus hominis type 2 in the development of cervical cancer.", "contents": "Antibodies to herpesvirus hominis types 1 and 2 among women with neoplastic change of uterine cervix. The occurrence of antibodies to herpesvirus hominis types 1 and 2 was studied in Finland among patients with a neoplastic change of the uterine cervix. The following groups were studied: 220 patients with malignant or premalignant lesions of the uterine cervix, 143 control patients matched for age, socioeconomic level, marital status, home district and number of deliveries and 82 patients with breast or stomach cancer. Antibodies to HVH types 1 and 2 were determined using the neutralization test. Sera showing an index of less than or equal to 100 were accepted as positive to type 1 and those of greater than or equal to 85 as positive to type 2. Among patients with a neoplastic change of the uterine cervix the frequency of type 1 antibodies varied between 70% and 79%. In the control group the frequency was 84% and among patients with some other malignancy 91%. These differences in the frequencies of type 1 antibody were not statistically significant. Type 2 antibodies were present in 35 to 47% among dysplasia and malignancy of the cervix. In the control group it was 18% and in other malignancies 20%. The differences between these groups and the controls were almost significant, significant and highly significant, respectively. Differences could also be observed in the distribution of neutralization indexes. The average index calculated from all sera was 48 both in the control group and in the group of other malignancies, while in sera of patients with dysplasia, carcinoma in situ and invasive carcinoma the respective vlaues were 70, 66 and 79. The results are discussed in terms of the role of herpesvirus hominis type 2 in the development of cervical cancer."} {"id": "PMID:173132", "title": "Inhibitory processes in the medial geniculate body.", "content": "Inhibition in the medial geniculate body was studied with a double click technique. A conditioning click caused a marked inhibition of field potentials and unit discharges to a subsequent test click. Cyclic inhibition with a period of about 150 ms was seen in the medial geniculate body and the auditory cortex, but not in the inferior colliculus. The postsynaptic excitability was tested by recording from the killed ends of the thalamocortical fibres. A preceding click reduced the direct response to a test stimulus delivered to the medial geniculate body indicating the presence of postsynaptic inhibition. The excitability of the fibres from the inferior colliculus terminating in the medial geniculate body was tested with a modified Wall (1958) method. The results suggest the presence of a presynaptic inhibitory mechanism in the medial geniculate body. The techniques employed do not allow an estimation of the relative contribution of the two inhibitory mechanisms to the inhibition at the medial geniculate level.", "contents": "Inhibitory processes in the medial geniculate body. Inhibition in the medial geniculate body was studied with a double click technique. A conditioning click caused a marked inhibition of field potentials and unit discharges to a subsequent test click. Cyclic inhibition with a period of about 150 ms was seen in the medial geniculate body and the auditory cortex, but not in the inferior colliculus. The postsynaptic excitability was tested by recording from the killed ends of the thalamocortical fibres. A preceding click reduced the direct response to a test stimulus delivered to the medial geniculate body indicating the presence of postsynaptic inhibition. The excitability of the fibres from the inferior colliculus terminating in the medial geniculate body was tested with a modified Wall (1958) method. The results suggest the presence of a presynaptic inhibitory mechanism in the medial geniculate body. The techniques employed do not allow an estimation of the relative contribution of the two inhibitory mechanisms to the inhibition at the medial geniculate level."} {"id": "PMID:173136", "title": "Histopathological studies on the tumourlet of the lung with special reference to the cytogenesis of proliferating cells.", "content": "Eight foci of tumourlets of the lung and one allied lesion obtained from autopsy cases were histologically examined. The tumourlet of the lung consisted of epithelial cells and was considered to be a benign lesion. Small sized-lesion, uniformity of proliferating cells with very few mitosis and existence of associated lung lesions were documented as characteristic findings. However, the histopathogenesis of the tumourlet was not fully clarified. It was found that proliferating cells of tumourlets often show argyrophilia and contain numerous neurosecretory-like granules in their cytoplasm. These characteristics are very similar to Kultschitzky-like cells of the lung.", "contents": "Histopathological studies on the tumourlet of the lung with special reference to the cytogenesis of proliferating cells. Eight foci of tumourlets of the lung and one allied lesion obtained from autopsy cases were histologically examined. The tumourlet of the lung consisted of epithelial cells and was considered to be a benign lesion. Small sized-lesion, uniformity of proliferating cells with very few mitosis and existence of associated lung lesions were documented as characteristic findings. However, the histopathogenesis of the tumourlet was not fully clarified. It was found that proliferating cells of tumourlets often show argyrophilia and contain numerous neurosecretory-like granules in their cytoplasm. These characteristics are very similar to Kultschitzky-like cells of the lung."} {"id": "PMID:173137", "title": "Histopathological studies on experimentally induced pulmonary adenomatosis in guinea-pig lungs.", "content": "The main purpose of our experimental series was to induce, in experimental animals, diffuse pulmonary fibrosis resembling that in human lungs. In the lungs of guinea-pigs injected with a soluble immune complex and continuously exposed to a 40-60 per cent oxygen-rich atmosphere, diffuse pulmonary fibrosis occurred in many cases in the course of 2 to 3 months after the injection. After the 100th experimental day, multiple foci of pulmonary adenomatosis occurred. The morphology was similar to that of Jaagsiekte. Electron microscopic observations revealed that these hyperplastic cells originated from type II pneumoncytes.", "contents": "Histopathological studies on experimentally induced pulmonary adenomatosis in guinea-pig lungs. The main purpose of our experimental series was to induce, in experimental animals, diffuse pulmonary fibrosis resembling that in human lungs. In the lungs of guinea-pigs injected with a soluble immune complex and continuously exposed to a 40-60 per cent oxygen-rich atmosphere, diffuse pulmonary fibrosis occurred in many cases in the course of 2 to 3 months after the injection. After the 100th experimental day, multiple foci of pulmonary adenomatosis occurred. The morphology was similar to that of Jaagsiekte. Electron microscopic observations revealed that these hyperplastic cells originated from type II pneumoncytes."} {"id": "PMID:173134", "title": "Congenital stapes fixation, symphalangism and syndactylia.", "content": "An autosomal dominant hereditary syndrome is described consisting of congenital deafness, characteristic finger and toe deformities, with absence of the proximal interphalangeal joint together with syndactylia. The syndrome has been observed in 5 members of a Danish family, and the study confirms the autosomal dominant trait.", "contents": "Congenital stapes fixation, symphalangism and syndactylia. An autosomal dominant hereditary syndrome is described consisting of congenital deafness, characteristic finger and toe deformities, with absence of the proximal interphalangeal joint together with syndactylia. The syndrome has been observed in 5 members of a Danish family, and the study confirms the autosomal dominant trait."} {"id": "PMID:173138", "title": "Tumor of glomus jugulare report of a case.", "content": "A typical case of glomus jugulare tumor was presented. This 42-year-old man suffering from a left-sided impaired hearing progressive over a five year period was found to have a small hemorrhagic polypoid tumor in the left external auditory canal. After repeated surgical treatments the tumor removed was light and electron microscopically diagnosed as glomus jugulare tumor which corresponded to the 13th case in this country. The implication that this tumor may constitute a distinctive group of tumor among the neuroendocrine tumors from other sites was discussed from the facts of the presence of a large number of rather small argyrophilic granules of secretory type in the cytoplasm of tumor cells including the present case and of the appearance of increasing cases with functioning glomus jugulare tumor secreting catecholamine in the recent medical literature.", "contents": "Tumor of glomus jugulare report of a case. A typical case of glomus jugulare tumor was presented. This 42-year-old man suffering from a left-sided impaired hearing progressive over a five year period was found to have a small hemorrhagic polypoid tumor in the left external auditory canal. After repeated surgical treatments the tumor removed was light and electron microscopically diagnosed as glomus jugulare tumor which corresponded to the 13th case in this country. The implication that this tumor may constitute a distinctive group of tumor among the neuroendocrine tumors from other sites was discussed from the facts of the presence of a large number of rather small argyrophilic granules of secretory type in the cytoplasm of tumor cells including the present case and of the appearance of increasing cases with functioning glomus jugulare tumor secreting catecholamine in the recent medical literature."} {"id": "PMID:173133", "title": "Cochlear innervation in the guinea pig. II. The spiral tunnel bundle.", "content": "The organization of nerve fibers in the spiral tunnel bundle (STB) of the guinea pig organ of Corti has been studied by light and electron microscopy. In the basal turn STB fibers were found to run toward the base or apex in about equal numbers while in the upper turns they ran predominantly in an apical direction. Long spiral fascicles of 100 microns or more in length were abundant in the third and fourth turns, but were rarely seen in the lower turns. No synaptic contacts between tunnel bundle fibers could be found and no afferent nerve fibers were seen in the bundle. Furthermore, interruption of the efferent nerve supply resulted in complete degeneration of the STB. The tunnel bundle does not, therefore, appear to be a site of synaptic interaction between afferent and efferent neutral elements.", "contents": "Cochlear innervation in the guinea pig. II. The spiral tunnel bundle. The organization of nerve fibers in the spiral tunnel bundle (STB) of the guinea pig organ of Corti has been studied by light and electron microscopy. In the basal turn STB fibers were found to run toward the base or apex in about equal numbers while in the upper turns they ran predominantly in an apical direction. Long spiral fascicles of 100 microns or more in length were abundant in the third and fourth turns, but were rarely seen in the lower turns. No synaptic contacts between tunnel bundle fibers could be found and no afferent nerve fibers were seen in the bundle. Furthermore, interruption of the efferent nerve supply resulted in complete degeneration of the STB. The tunnel bundle does not, therefore, appear to be a site of synaptic interaction between afferent and efferent neutral elements."} {"id": "PMID:173141", "title": "High-energy protons in the postoperative treatment of malignant glioma.", "content": "Fractionated irradiation with high-energy protons was given postoperatively to seven patients with malignant glioma. In four cases in which detailed microscopic examinations were performed, radiation induced tumour necrosis was evident but in all four cases viable tumour cells were also observed. No abnormalities that could be attributed to radiation were observed in brain tissue free from tumour. The therapeutic results were comparable to the results achieved by other modern therapies. The results support the view that the RBE of high-energy protons is similar to that for 60Co radiation. It is suggested that a larger radiation dose, delivered by a homogeneous, well-defined proton field could possibly result in an improved therapeutic result without undue risk of injury to normal brain tissue.", "contents": "High-energy protons in the postoperative treatment of malignant glioma. Fractionated irradiation with high-energy protons was given postoperatively to seven patients with malignant glioma. In four cases in which detailed microscopic examinations were performed, radiation induced tumour necrosis was evident but in all four cases viable tumour cells were also observed. No abnormalities that could be attributed to radiation were observed in brain tissue free from tumour. The therapeutic results were comparable to the results achieved by other modern therapies. The results support the view that the RBE of high-energy protons is similar to that for 60Co radiation. It is suggested that a larger radiation dose, delivered by a homogeneous, well-defined proton field could possibly result in an improved therapeutic result without undue risk of injury to normal brain tissue."} {"id": "PMID:173135", "title": "Effects of cholinergic agonists and antagonists of nucleus vestibularis lateralis unit discharge to vestibular nerve stimulation in the cat.", "content": "Unit discharge in nucleus vestibularis (NVL) was studied in locally anesthetized cats. The mean firing rate +/-S.E. of spontaneous unitary discharges of NVL neurons was 19.8+/-0.9 Hz and that of spinal-transected animals was 18.0+/-1.6 Hz. The mean firing rate of these neurons in animals with cerebellum ablation and the administration of scopolamine in a dose of 0.5 mg/kg i.v. was relatively low. After administration of physostigmine in a dose of 25 mug/kg i.v. the firing rate was enhanced. The effects of physostigmine were antagonized by scopolamine. About 95% of NVL neurons activated by single electrical shocks to the ipsilateral vestibular nerve showed regular firing following administration of physostigmine. These neurons changed to a gamma distribution at lambda=2 following administration of scopolamine.", "contents": "Effects of cholinergic agonists and antagonists of nucleus vestibularis lateralis unit discharge to vestibular nerve stimulation in the cat. Unit discharge in nucleus vestibularis (NVL) was studied in locally anesthetized cats. The mean firing rate +/-S.E. of spontaneous unitary discharges of NVL neurons was 19.8+/-0.9 Hz and that of spinal-transected animals was 18.0+/-1.6 Hz. The mean firing rate of these neurons in animals with cerebellum ablation and the administration of scopolamine in a dose of 0.5 mg/kg i.v. was relatively low. After administration of physostigmine in a dose of 25 mug/kg i.v. the firing rate was enhanced. The effects of physostigmine were antagonized by scopolamine. About 95% of NVL neurons activated by single electrical shocks to the ipsilateral vestibular nerve showed regular firing following administration of physostigmine. These neurons changed to a gamma distribution at lambda=2 following administration of scopolamine."} {"id": "PMID:173139", "title": "The effect of acute exercise on plasma corticosterone in the ovariectomized rat.", "content": "Levels of plasma corticosterone were determined by a fluorometric method in female rats, subjected to acute treadmill exercise. It was found that physical exercise causes a twofold rise in the plasma corticosterone concentration. This increase was slightly lower in the ovariectomized animals. Duration of the effort until exhaustion varied with age und hormonal status of the animals.", "contents": "The effect of acute exercise on plasma corticosterone in the ovariectomized rat. Levels of plasma corticosterone were determined by a fluorometric method in female rats, subjected to acute treadmill exercise. It was found that physical exercise causes a twofold rise in the plasma corticosterone concentration. This increase was slightly lower in the ovariectomized animals. Duration of the effort until exhaustion varied with age und hormonal status of the animals."} {"id": "PMID:173148", "title": "Serum lipoprotein composition in different types of hyperlipoproteinemia.", "content": "Fasting serum lipoproteins (LP) were separated into VLDL, LDL and HDL by ultracentrifugation and the content of cholesterol and triglycerides analyzed in each LP class in 69 consecutive men attending a lipid clinic. The effect of using different cut off points in the definition of HLP was discussed. It was pointed out that by using lower values for the cut off points there is only an increase in the number of subjects with hyperlipoproteinemia (HLP) but also shifts in the proportions between the various types of HLP, particularly with increase in the amount of types IIB and IV. In addition to the LP abnormalities inherent in the definition of each type of HLP other LP abnormalities were observed. Thus type IIA HLP had cholesterol rich VLDL with an increased ratio cholesterol/triglycerides. The types of HLP with increased VLDL triglycerides had characteristic changes in both LDL and HDL. For LDL its triglyceride content was increased and HDL showed a lowering of its cholesterol content and a rise in triglycerides. These changes were more pronounced the higher the VLDL triglyceride concentration was. Both normo- and hyperlipoproteinemic subjects having the second pre-beta LP on agarose gel electrophoresis of the VLDL fraction called LPB (Late Pre Beta) had two characteristic LP features. VLDL had an increased cholesterol/triglyceride ratio. LDL had a raised triglyceride content. The relation of LPB to so called intermediary particles was discussed. When the SPB (Sinking Pre Beta) LP variant was present this had negligible effects on the LP composition. Type IIA was present in 14 percent of the 609 men. None had tendinous xanthomata. The LP pattern of this common type IIA was compared to the LP pattern of the uncommon type IIA where tendinous xanthomata are present, called IIA-X. Type IIA-X had much higher LDL cholesterol and in relation to the triglyceride content a more cholesterol rich LDL. Furthermore type IIA-X had lower VLDL lipids than the common type IIA, but type IIA-X was more cholesterol rich. The differences in clinical appearance as well as in quantitative and qualitative LP composition between the common type IIA and type IIA-X makes it important to separate these two types of HLP from each other.", "contents": "Serum lipoprotein composition in different types of hyperlipoproteinemia. Fasting serum lipoproteins (LP) were separated into VLDL, LDL and HDL by ultracentrifugation and the content of cholesterol and triglycerides analyzed in each LP class in 69 consecutive men attending a lipid clinic. The effect of using different cut off points in the definition of HLP was discussed. It was pointed out that by using lower values for the cut off points there is only an increase in the number of subjects with hyperlipoproteinemia (HLP) but also shifts in the proportions between the various types of HLP, particularly with increase in the amount of types IIB and IV. In addition to the LP abnormalities inherent in the definition of each type of HLP other LP abnormalities were observed. Thus type IIA HLP had cholesterol rich VLDL with an increased ratio cholesterol/triglycerides. The types of HLP with increased VLDL triglycerides had characteristic changes in both LDL and HDL. For LDL its triglyceride content was increased and HDL showed a lowering of its cholesterol content and a rise in triglycerides. These changes were more pronounced the higher the VLDL triglyceride concentration was. Both normo- and hyperlipoproteinemic subjects having the second pre-beta LP on agarose gel electrophoresis of the VLDL fraction called LPB (Late Pre Beta) had two characteristic LP features. VLDL had an increased cholesterol/triglyceride ratio. LDL had a raised triglyceride content. The relation of LPB to so called intermediary particles was discussed. When the SPB (Sinking Pre Beta) LP variant was present this had negligible effects on the LP composition. Type IIA was present in 14 percent of the 609 men. None had tendinous xanthomata. The LP pattern of this common type IIA was compared to the LP pattern of the uncommon type IIA where tendinous xanthomata are present, called IIA-X. Type IIA-X had much higher LDL cholesterol and in relation to the triglyceride content a more cholesterol rich LDL. Furthermore type IIA-X had lower VLDL lipids than the common type IIA, but type IIA-X was more cholesterol rich. The differences in clinical appearance as well as in quantitative and qualitative LP composition between the common type IIA and type IIA-X makes it important to separate these two types of HLP from each other."} {"id": "PMID:173149", "title": "The heritable hyperlipoproteinemias and atherosclerosis.", "content": "1. The genetic hyperlipoproteinemias are common, are easily diagnosed and are often expressed in children or in infants. 2. Familial combined hyperlipidemia, hypercholesterolemia and hypertriglyceridemia are all associated with a markedly augmented atherosclerotic cardiovascular event rate. 3. The clinical importance of early diagnosis, family screening, and lipid sampling in high risk or free living populations must be emphasized. 4. Exciting progress at a biochemical molecular level (in tissue culture, for example) provides better understanding of the genetic hyperlipoproteinemias and possible avenues for its better therapy.", "contents": "The heritable hyperlipoproteinemias and atherosclerosis. 1. The genetic hyperlipoproteinemias are common, are easily diagnosed and are often expressed in children or in infants. 2. Familial combined hyperlipidemia, hypercholesterolemia and hypertriglyceridemia are all associated with a markedly augmented atherosclerotic cardiovascular event rate. 3. The clinical importance of early diagnosis, family screening, and lipid sampling in high risk or free living populations must be emphasized. 4. Exciting progress at a biochemical molecular level (in tissue culture, for example) provides better understanding of the genetic hyperlipoproteinemias and possible avenues for its better therapy."} {"id": "PMID:173151", "title": "Lipoproteins and lipid transport.", "content": "Continued advances in the delineation of pathways of lipid transport in lipoproteins now provide substantial information on all phases of plasma triglyceride transport. Analysis of certain genetic human disorders, together with studies in experimental animals, has begun to show how lipoproteins transport cholesterol as esters of long chain fatty acids. Both triglycerides and cholesterol are esters of long chain fatty acids. Both triglycerides and cholesteryl esters are transported in the \"core\" of lipoproteins, but the polar lipids and the apoproteins at the aqueous interface critically determine the interactions with enzymes and cellular receptors that control this complex transport system. Differences in pathways as well as in rates of lipid transport appear to underlie the large interspecies variations in lipoprotein concentrations.", "contents": "Lipoproteins and lipid transport. Continued advances in the delineation of pathways of lipid transport in lipoproteins now provide substantial information on all phases of plasma triglyceride transport. Analysis of certain genetic human disorders, together with studies in experimental animals, has begun to show how lipoproteins transport cholesterol as esters of long chain fatty acids. Both triglycerides and cholesterol are esters of long chain fatty acids. Both triglycerides and cholesteryl esters are transported in the \"core\" of lipoproteins, but the polar lipids and the apoproteins at the aqueous interface critically determine the interactions with enzymes and cellular receptors that control this complex transport system. Differences in pathways as well as in rates of lipid transport appear to underlie the large interspecies variations in lipoprotein concentrations."} {"id": "PMID:173152", "title": "The cockerel as an animal model for atherosclerosis research.", "content": "The chicken is a good animal model for the study of atherosclerosis research because it is: 1. Omnivorous. 2. Small and suitable for prolonged laboratory investigation. 3. Able to develop spontaneous atherosclerosis. 4. Capable of producing atherosclerosis after cholesterol feeding with elevated hypercholesterolemia. A diet of 1/4% cholesterol plus 5% cottonseed oil added to starter-grower-mash resulted in aortic atherosclerosis with a slight but significant increase in plasma cholesterol. 5. Plasma levels of cholesterol and triglyceride are similar to those in humans. 6. Lipid composition of high and low density lipoproteins as well as chylomicrons resembles those of humans. 7. Has been noted that there is no essential difference between vascular lesions seen in chickens as a result of cholesterol diet and that of atherosclerosis observed in man.", "contents": "The cockerel as an animal model for atherosclerosis research. The chicken is a good animal model for the study of atherosclerosis research because it is: 1. Omnivorous. 2. Small and suitable for prolonged laboratory investigation. 3. Able to develop spontaneous atherosclerosis. 4. Capable of producing atherosclerosis after cholesterol feeding with elevated hypercholesterolemia. A diet of 1/4% cholesterol plus 5% cottonseed oil added to starter-grower-mash resulted in aortic atherosclerosis with a slight but significant increase in plasma cholesterol. 5. Plasma levels of cholesterol and triglyceride are similar to those in humans. 6. Lipid composition of high and low density lipoproteins as well as chylomicrons resembles those of humans. 7. Has been noted that there is no essential difference between vascular lesions seen in chickens as a result of cholesterol diet and that of atherosclerosis observed in man."} {"id": "PMID:173168", "title": "How good is thermography in breast cancer screening?", "content": "With the present level of experience and with current equipment, thermography does not seem sufficiently reliable to substitute for either clinical examination or mammography in breast cancer detection. It is, however, of adjunctive value and can be used in frequent screening and in younger individuals. Women with positive thermograms should be followed more closely, both clinically and radiographically, than the average patient.", "contents": "How good is thermography in breast cancer screening? With the present level of experience and with current equipment, thermography does not seem sufficiently reliable to substitute for either clinical examination or mammography in breast cancer detection. It is, however, of adjunctive value and can be used in frequent screening and in younger individuals. Women with positive thermograms should be followed more closely, both clinically and radiographically, than the average patient."} {"id": "PMID:173169", "title": "Metabolic and cardiovascular abnormalities in patients with peripheral arterial disease.", "content": "Twenty-eight consecutive patients of an average age of 63 years with intermittent claudication secondary to underlying peripheral arterial disease were studied for evidence of metabolic or other cardiovascular abnormalities and the results obtained were compared with those of 28 matched control subjects free of vascular disease. Patients with peripheral arterial disease had significantly higher levels of systolic and diastolic blood pressure, a greater incidence of ECG abnormalities, lipoprotein abnormalities, elevated serum triglycerides, and serum copper. The incidence of smoking and abnormal glucose tolerance, while higher in peripheral arterial disease patients, was not statistically significant. Hematocrit and serum cholesterol levels were nearly indentical in both groups of patients. Twenty-six of the 28 patiens with peripheral arterial disease had either a cardiovascular or a metabolic abnormality, indicating the high incidence of multisystem illness in this disorder. The epidemiologic data in peripheral arterial disease are similar to those in coronary artery disease but some measurements contrast sharply, such as the apparent normal level of serum cholesterol in patients with peripheral arterial diseases.", "contents": "Metabolic and cardiovascular abnormalities in patients with peripheral arterial disease. Twenty-eight consecutive patients of an average age of 63 years with intermittent claudication secondary to underlying peripheral arterial disease were studied for evidence of metabolic or other cardiovascular abnormalities and the results obtained were compared with those of 28 matched control subjects free of vascular disease. Patients with peripheral arterial disease had significantly higher levels of systolic and diastolic blood pressure, a greater incidence of ECG abnormalities, lipoprotein abnormalities, elevated serum triglycerides, and serum copper. The incidence of smoking and abnormal glucose tolerance, while higher in peripheral arterial disease patients, was not statistically significant. Hematocrit and serum cholesterol levels were nearly indentical in both groups of patients. Twenty-six of the 28 patiens with peripheral arterial disease had either a cardiovascular or a metabolic abnormality, indicating the high incidence of multisystem illness in this disorder. The epidemiologic data in peripheral arterial disease are similar to those in coronary artery disease but some measurements contrast sharply, such as the apparent normal level of serum cholesterol in patients with peripheral arterial diseases."} {"id": "PMID:173170", "title": "Idiopathic cardiomyopathy and skeletal muscle abnormality.", "content": "The skeletal muscle of three cases presenting with idiopathic congestive cardiomyopathy has been studied, histologically, histochemically, ultramicroscopically, and electromyographically. In all three there is clinical evidence of skeletal muscle weakness, and in all three, pathologic changes were found in the muscle. These changes were different in each case and varied from mitochondrial myopathy to spinal atrophy to vacuolar myopathy. Other reported cases of cardiomyopathy demonstrating skeletal muscle pathology are discussed.", "contents": "Idiopathic cardiomyopathy and skeletal muscle abnormality. The skeletal muscle of three cases presenting with idiopathic congestive cardiomyopathy has been studied, histologically, histochemically, ultramicroscopically, and electromyographically. In all three there is clinical evidence of skeletal muscle weakness, and in all three, pathologic changes were found in the muscle. These changes were different in each case and varied from mitochondrial myopathy to spinal atrophy to vacuolar myopathy. Other reported cases of cardiomyopathy demonstrating skeletal muscle pathology are discussed."} {"id": "PMID:173171", "title": "On acupuncture analgesia and the mechanism of pain.", "content": "The effect on the experimental tooth pain threshold of conditioning electrical stimulation via needles or surface electrodes applied to the hands and cheeks was studied in 34 dental students. Conditioning stimulation with 2/sec. gave a slowly increasing pain threshold followed by a slow return to the control level in the post-conditioning period. In each individual the amplitude of the threshold increase was reproduceable. It was concluded that these effects are not due to motivational but to more basic neurophysiological mechanisms. The pain threshold was increased mainly by segmental conditioning stimulation; segmentally unrelated stimulation gave usually only small effects. Conditioning stimulation with 100/sec. produced only a strict segmental short-lasting effect. Effects with characteristics of both 2/sec. and 100/sec. were obtained by conditioning at 10/sec. It is suggested that the transmission of impulses from the pain afferents to ascending pathways is controlled at the segmental level by (a) presynaptic inhibition within the group of afferents giving rise to the flexion reflex of which the pain afferents are assumed to be a part; (b) postsynaptic inhibition between alternate pathway excited by flexion reflex afferents; and (c) descending control from supraspinal systems which may utilize similar segmental mechanisms as the primary afferents.", "contents": "On acupuncture analgesia and the mechanism of pain. The effect on the experimental tooth pain threshold of conditioning electrical stimulation via needles or surface electrodes applied to the hands and cheeks was studied in 34 dental students. Conditioning stimulation with 2/sec. gave a slowly increasing pain threshold followed by a slow return to the control level in the post-conditioning period. In each individual the amplitude of the threshold increase was reproduceable. It was concluded that these effects are not due to motivational but to more basic neurophysiological mechanisms. The pain threshold was increased mainly by segmental conditioning stimulation; segmentally unrelated stimulation gave usually only small effects. Conditioning stimulation with 100/sec. produced only a strict segmental short-lasting effect. Effects with characteristics of both 2/sec. and 100/sec. were obtained by conditioning at 10/sec. It is suggested that the transmission of impulses from the pain afferents to ascending pathways is controlled at the segmental level by (a) presynaptic inhibition within the group of afferents giving rise to the flexion reflex of which the pain afferents are assumed to be a part; (b) postsynaptic inhibition between alternate pathway excited by flexion reflex afferents; and (c) descending control from supraspinal systems which may utilize similar segmental mechanisms as the primary afferents."} {"id": "PMID:173172", "title": "Use of immunoperoxidase on brain tissue for the rapid diagnosis of herpes encephalitis.", "content": "An indirect immunoperoxidase method to detect herpes simplex viral antigen in brain cell suspensions from patients suspected to have herpes encephalitis is described. The method is rapid, reliable and specific, and successfully identified the herpes virus infected cells in four of five culture-proven cases. There was one false-negative reaction, but no false-positive. The immunoperoxidase technic offers a number of advantages over immunofluorescence for routine diagnosis.", "contents": "Use of immunoperoxidase on brain tissue for the rapid diagnosis of herpes encephalitis. An indirect immunoperoxidase method to detect herpes simplex viral antigen in brain cell suspensions from patients suspected to have herpes encephalitis is described. The method is rapid, reliable and specific, and successfully identified the herpes virus infected cells in four of five culture-proven cases. There was one false-negative reaction, but no false-positive. The immunoperoxidase technic offers a number of advantages over immunofluorescence for routine diagnosis."} {"id": "PMID:173173", "title": "Fluorescent antibody studies of alpha-1-antitrypsin in adult human lung.", "content": "The histologic distribution of alpha-1-antitrypsin in frozen sections prepared from four specimens of human lung was determined by the indirect fluorescent antibody technic. Three of the specimens were obtained directly from surgical procedures and were peripheral tissue excised with tumors. The tumors were a mixed-cell \"scar cancer\" (Case 1), a bronchiolar carcinoma (Case 2), and a benign hemartoma (Case 3). The fourth specimen (Case 4) was obtained at autopsy following death by myocardial infarction. Specific fluorescence for alpha-1-antitrypsin was observed lining the terminal airways and alveoli throughout the sections from Cases 1 and 4. In specimens from Cases 2 and 3, a few focal areas of specific fluorescence were observed. The results of this study suggest that alpha-1-antitrypsin may be distributed in lung in variable concentration in association with pulmonary surfactant.", "contents": "Fluorescent antibody studies of alpha-1-antitrypsin in adult human lung. The histologic distribution of alpha-1-antitrypsin in frozen sections prepared from four specimens of human lung was determined by the indirect fluorescent antibody technic. Three of the specimens were obtained directly from surgical procedures and were peripheral tissue excised with tumors. The tumors were a mixed-cell \"scar cancer\" (Case 1), a bronchiolar carcinoma (Case 2), and a benign hemartoma (Case 3). The fourth specimen (Case 4) was obtained at autopsy following death by myocardial infarction. Specific fluorescence for alpha-1-antitrypsin was observed lining the terminal airways and alveoli throughout the sections from Cases 1 and 4. In specimens from Cases 2 and 3, a few focal areas of specific fluorescence were observed. The results of this study suggest that alpha-1-antitrypsin may be distributed in lung in variable concentration in association with pulmonary surfactant."} {"id": "PMID:173175", "title": "The epidemiology of cancer of the breast.", "content": "A summary of the most relevant facts and hypotheses concerning breast cancer epidemiology is made. It is suggested that the statistical associations with suspected etiologic factors might be diluted by the heterogeneity of the disease. It is suggested that breast cancer is composed of several epidemiologic sub-entities determined by such factors as familial aggregation, histology and hormone profile.", "contents": "The epidemiology of cancer of the breast. A summary of the most relevant facts and hypotheses concerning breast cancer epidemiology is made. It is suggested that the statistical associations with suspected etiologic factors might be diluted by the heterogeneity of the disease. It is suggested that breast cancer is composed of several epidemiologic sub-entities determined by such factors as familial aggregation, histology and hormone profile."} {"id": "PMID:173176", "title": "Cellular composition of the nipple aspirate specimen of breast fluid. II. Abnormal findings.", "content": "Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions.", "contents": "Cellular composition of the nipple aspirate specimen of breast fluid. II. Abnormal findings. Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions."} {"id": "PMID:173177", "title": "Breast specimen radiography. Obligatory, adjuvant and investigative.", "content": "The development of mammography and that of breast specimen radiography, which have paralleled one another, are reviewed. The preparation of radiographs of breast specimens is obligatory when biopsy is performed for purely mammographic indications and when no palpable mass is present. Such cases are being encountered with increasing frequency because of the development of centers for breast cancer screening. Close collaboration among pathologists, radiologists and surgeons and precise attention to procedural detail are necessities wherever this situation arises. The application of specimen radiography as a routine to all breast specimens is regarded as an adjunct to gross examination. While useful, its yield of otherwise undetected occult carcinoma is low. Whether other advantages outweigh the cost appears to be a matter for individual decision. Investigative uses of breast specimen radiography have received little attention. Some possible applications are suggested.", "contents": "Breast specimen radiography. Obligatory, adjuvant and investigative. The development of mammography and that of breast specimen radiography, which have paralleled one another, are reviewed. The preparation of radiographs of breast specimens is obligatory when biopsy is performed for purely mammographic indications and when no palpable mass is present. Such cases are being encountered with increasing frequency because of the development of centers for breast cancer screening. Close collaboration among pathologists, radiologists and surgeons and precise attention to procedural detail are necessities wherever this situation arises. The application of specimen radiography as a routine to all breast specimens is regarded as an adjunct to gross examination. While useful, its yield of otherwise undetected occult carcinoma is low. Whether other advantages outweigh the cost appears to be a matter for individual decision. Investigative uses of breast specimen radiography have received little attention. Some possible applications are suggested."} {"id": "PMID:173178", "title": "Staging in the therapy of cancer of the breast.", "content": "Clinical and pathologic staging of breast cancer are discussed. A new pathologic staging system is presented: numerical scores are assigned, in cases of infiltrating ductal carcinoma of no specific subtype, for tumor size, histologic grade, amount of stromal infilttration, vascular invasion, axillary lymph nodal metastases, and sinus histiocytosis in axillary lymph nodes. Staging by this system correlates well with survival in cases treated by radical mastectomy. The essential features to be studied in pathologic specimens of breast cancer are also indicated.", "contents": "Staging in the therapy of cancer of the breast. Clinical and pathologic staging of breast cancer are discussed. A new pathologic staging system is presented: numerical scores are assigned, in cases of infiltrating ductal carcinoma of no specific subtype, for tumor size, histologic grade, amount of stromal infilttration, vascular invasion, axillary lymph nodal metastases, and sinus histiocytosis in axillary lymph nodes. Staging by this system correlates well with survival in cases treated by radical mastectomy. The essential features to be studied in pathologic specimens of breast cancer are also indicated."} {"id": "PMID:173180", "title": "Endocrinology in cancer of the breast. Status and prospects.", "content": "Breast cancer is the result of a multistage carcinogenic process. Initiation, promotion, dependency and autonomy make up a sequence of experimentally distinguishable phases of this process. Progression--the transition from dependency on hormonal support to autonomy--is demonstrable clinically. High-affinity saturatable estrogen binding by breast cancer cytosols distinguishes endocrine-responsive mammary neoplasms from autonomous breast cancers. Approximately 70% of neoplasms containing estrogen-recepor protein at a level of 2.5 femtomoles per mg. protein or higher regress after endocrine ablation (ovariectomy in premenopausal women; adrenalectomy or hypophysectomy in postmenopausal women). Only about 5% of neoplasms lacking the receptor will respond to these maneuvers. Estrogen-receptor content also predicts clinically for estrogen and androgen responsiveness, and experimentally for prolactin dependency. Fifty per cent of primary breast cancers in women are receptor-positive. Normal breast tissue and benign breast lesions characteristically lack receptor protein. The receptor proteins appear to be induced in neoplastic cells during mammary carcinogenesis in endocrinologic settings where non-cancerous breast cells do not contain free receptor in large amounts and fail to manifest endocrinologic growth stimulation. Implications of these findings for endocrinologic management of disseminated mammary cancer, adjuvant therapy, and breast cancer prevention are discussed.", "contents": "Endocrinology in cancer of the breast. Status and prospects. Breast cancer is the result of a multistage carcinogenic process. Initiation, promotion, dependency and autonomy make up a sequence of experimentally distinguishable phases of this process. Progression--the transition from dependency on hormonal support to autonomy--is demonstrable clinically. High-affinity saturatable estrogen binding by breast cancer cytosols distinguishes endocrine-responsive mammary neoplasms from autonomous breast cancers. Approximately 70% of neoplasms containing estrogen-recepor protein at a level of 2.5 femtomoles per mg. protein or higher regress after endocrine ablation (ovariectomy in premenopausal women; adrenalectomy or hypophysectomy in postmenopausal women). Only about 5% of neoplasms lacking the receptor will respond to these maneuvers. Estrogen-receptor content also predicts clinically for estrogen and androgen responsiveness, and experimentally for prolactin dependency. Fifty per cent of primary breast cancers in women are receptor-positive. Normal breast tissue and benign breast lesions characteristically lack receptor protein. The receptor proteins appear to be induced in neoplastic cells during mammary carcinogenesis in endocrinologic settings where non-cancerous breast cells do not contain free receptor in large amounts and fail to manifest endocrinologic growth stimulation. Implications of these findings for endocrinologic management of disseminated mammary cancer, adjuvant therapy, and breast cancer prevention are discussed."} {"id": "PMID:173181", "title": "Primary hypothyroidism. Differentiation from primary hypopituitarism.", "content": "Five patients with growth failure but few other abnormal clinical signs are presented. Two were shown to have primary hypopituitarism, three had primary hypothyroidism. All received levothyroxine sodium and grew 7.0 to 12.5 cm during the first year and 6.2 to 8.7 cm during the second year of treatment. Three of the adolescent patients developed signs of signs of puberty within six to nine months of initiation of levothyroxine therapy. One hypopituitary patient had femoral epiphysial dysgenesis, hypopglycemia, and undescended testes. One hypothyroid patient had been treated for diabetes mellitus for 8.5 years and may be the youngest patient reported with such a disease combination. We conclude that in a few patients with growth failure without specific clinical signs, diagnosis and differentiation between primary hypothyroidism and primary hypopituitarism can only be made by specific endocrinologic testing.", "contents": "Primary hypothyroidism. Differentiation from primary hypopituitarism. Five patients with growth failure but few other abnormal clinical signs are presented. Two were shown to have primary hypopituitarism, three had primary hypothyroidism. All received levothyroxine sodium and grew 7.0 to 12.5 cm during the first year and 6.2 to 8.7 cm during the second year of treatment. Three of the adolescent patients developed signs of signs of puberty within six to nine months of initiation of levothyroxine therapy. One hypopituitary patient had femoral epiphysial dysgenesis, hypopglycemia, and undescended testes. One hypothyroid patient had been treated for diabetes mellitus for 8.5 years and may be the youngest patient reported with such a disease combination. We conclude that in a few patients with growth failure without specific clinical signs, diagnosis and differentiation between primary hypothyroidism and primary hypopituitarism can only be made by specific endocrinologic testing."} {"id": "PMID:173182", "title": "Prostaglandin E in cholera toxin-induced intestinal secretion. Lack of an intermediary role.", "content": "Prostaglandin E1 (PGE1) and cholera enterotoxin stimulate small-intestine mucosal adenylate cyclase and intestinal secretion of water and electrolytes. The previous suggestion that PGE may mediate cholera-toxin effects was explored in these studies. Closed rabbit jejunal loops were injected in vivo with cholera toxin and compared to similar loops in the same animal injected with buffer. Loop mucosal homogenates and intestinal secretions were analyzed by radioimmunoassay for cAMP and PGE concentrations. Cholera toxin produced significant increases in mucosal and intestinal fluid cAMP; however, there were no significant increases in PGE in the toxin-treated loops when compared to the control loops. In addition, there was no correlation between cAMP and PGE in the same samples. These studies indicate that cholera toxin stimulates intestinal cAMP anc secretion independent of PGE synthesis and provide evidence against a specific role for PGE in mediating cholera-toxin effects.", "contents": "Prostaglandin E in cholera toxin-induced intestinal secretion. Lack of an intermediary role. Prostaglandin E1 (PGE1) and cholera enterotoxin stimulate small-intestine mucosal adenylate cyclase and intestinal secretion of water and electrolytes. The previous suggestion that PGE may mediate cholera-toxin effects was explored in these studies. Closed rabbit jejunal loops were injected in vivo with cholera toxin and compared to similar loops in the same animal injected with buffer. Loop mucosal homogenates and intestinal secretions were analyzed by radioimmunoassay for cAMP and PGE concentrations. Cholera toxin produced significant increases in mucosal and intestinal fluid cAMP; however, there were no significant increases in PGE in the toxin-treated loops when compared to the control loops. In addition, there was no correlation between cAMP and PGE in the same samples. These studies indicate that cholera toxin stimulates intestinal cAMP anc secretion independent of PGE synthesis and provide evidence against a specific role for PGE in mediating cholera-toxin effects."} {"id": "PMID:173183", "title": "Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method.", "content": "An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.", "contents": "Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method. An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign."} {"id": "PMID:173184", "title": "Human erythrocyte galactokinase and galactose-1-phosphate uridylyltransferase: a population survey.", "content": "Erythrocyte (RBC) galactokinase (GALK) and galactose-1-phosphate uridylyl-transferase (GALT) activities were measured in a random sample of 1,700 (1.082 black and 618 white) pregnant women from the Philadelphia area to estimate the frequency of the genes GALKG and GALTG responsible for the two biochemically distinct forms of galactosemia. Blacks have significantly lower mean RBC GALK activities than whites (P less than .0005). The distribution of individual GALK activities for blacks differs from a normal distribution (X227=43.0, P less than .03) whereas that for whites does not (X224=25.5, P approximately equal to .30). These results are consistent with the thesis that reduced RBC GALK activity in blacks is due to the Philadelphia variant (GALKP), which is common in blacks and rare in whites. The frequency of heterozygotes (GALKG/GALKA, GALKG/GALKP) for GALK galactosemia observed in this sample is 1/340 for the total, 1/347 for blacks, and 1/309 for whites. The existence of the GALKP variant allele has been considered in this determination. However, because a method for distinguishing the GALKP and GALKG alleles became available only in the latter part of the study, the frequency of the GALK G allele in the black population may be underestimated. The mean RBC GALT activity for blacks is higher than that for whites, a difference that may be due to a higher frequency of the Duarte variant allele GALTD in whites. Heterozygotes (GALTG/GALTA) for GALT galactosemia were distinguished by family studies and starch gel electrophoresis from individuals who have half-normal RBC GALT activity due to the GALTD allele. The GALTG/GALTA frequency is 1/212 for the total, 1/217 for blacks, and 1/206 for whites. Of the 1,700 individuals surveyed three had atypically high RBC GALK activity, similar to that found in red blood cells of newborns.", "contents": "Human erythrocyte galactokinase and galactose-1-phosphate uridylyltransferase: a population survey. Erythrocyte (RBC) galactokinase (GALK) and galactose-1-phosphate uridylyl-transferase (GALT) activities were measured in a random sample of 1,700 (1.082 black and 618 white) pregnant women from the Philadelphia area to estimate the frequency of the genes GALKG and GALTG responsible for the two biochemically distinct forms of galactosemia. Blacks have significantly lower mean RBC GALK activities than whites (P less than .0005). The distribution of individual GALK activities for blacks differs from a normal distribution (X227=43.0, P less than .03) whereas that for whites does not (X224=25.5, P approximately equal to .30). These results are consistent with the thesis that reduced RBC GALK activity in blacks is due to the Philadelphia variant (GALKP), which is common in blacks and rare in whites. The frequency of heterozygotes (GALKG/GALKA, GALKG/GALKP) for GALK galactosemia observed in this sample is 1/340 for the total, 1/347 for blacks, and 1/309 for whites. The existence of the GALKP variant allele has been considered in this determination. However, because a method for distinguishing the GALKP and GALKG alleles became available only in the latter part of the study, the frequency of the GALK G allele in the black population may be underestimated. The mean RBC GALT activity for blacks is higher than that for whites, a difference that may be due to a higher frequency of the Duarte variant allele GALTD in whites. Heterozygotes (GALTG/GALTA) for GALT galactosemia were distinguished by family studies and starch gel electrophoresis from individuals who have half-normal RBC GALT activity due to the GALTD allele. The GALTG/GALTA frequency is 1/212 for the total, 1/217 for blacks, and 1/206 for whites. Of the 1,700 individuals surveyed three had atypically high RBC GALK activity, similar to that found in red blood cells of newborns."} {"id": "PMID:173185", "title": "Galactose tolerance studies of individuals with reduced galactose pathway activity.", "content": "The galactose tolerance of individuals with mutant genotypes affecting the activities of galactokinase (GALK) and galactose-1-phosphate uridylyltransferase (GALT) was examined. Genotypes studied were heterozygotes for the GALK and GALT forms of galactosemia, the Duarte-variant GALT, and Philadelphia-variant GALK alleles. The measurements used were urinary concentration of galactose during pregnancy in adults and in infants from the newborn period through the first 5 months of life; the rate of elimination of an intravenous infusion of galactose; and slit-lamp examination of the lens for evidence of cataracts. No unusual urinary excretions of galactose were noted in any of the age groups studied. Intravenous galactose tolerance tests were normal in all but two women, a mother and daughter heterozygous for the GALK-deficient form of galactosemia (GALKG/GALKA). Six other GALKG/GALKA subjects had normal tolerance studies. The intrafamilial consistency and interfamilial differences in the galactose tolerance of GALKG/GALKA individuals suggest heterogeneity of the genes responsible for the GALK-deficient form of galactosemia. Although subclinical cataracts were observed in several individuals, their significance relative to the mutant genotype cannot be resolved with the available data.", "contents": "Galactose tolerance studies of individuals with reduced galactose pathway activity. The galactose tolerance of individuals with mutant genotypes affecting the activities of galactokinase (GALK) and galactose-1-phosphate uridylyltransferase (GALT) was examined. Genotypes studied were heterozygotes for the GALK and GALT forms of galactosemia, the Duarte-variant GALT, and Philadelphia-variant GALK alleles. The measurements used were urinary concentration of galactose during pregnancy in adults and in infants from the newborn period through the first 5 months of life; the rate of elimination of an intravenous infusion of galactose; and slit-lamp examination of the lens for evidence of cataracts. No unusual urinary excretions of galactose were noted in any of the age groups studied. Intravenous galactose tolerance tests were normal in all but two women, a mother and daughter heterozygous for the GALK-deficient form of galactosemia (GALKG/GALKA). Six other GALKG/GALKA subjects had normal tolerance studies. The intrafamilial consistency and interfamilial differences in the galactose tolerance of GALKG/GALKA individuals suggest heterogeneity of the genes responsible for the GALK-deficient form of galactosemia. Although subclinical cataracts were observed in several individuals, their significance relative to the mutant genotype cannot be resolved with the available data."} {"id": "PMID:173186", "title": "Evaluation of a possible sex difference in recombination for the ABO-AK linkage.", "content": "Thirty-five informative families were scored for linkage between the ABO and AK loci. The recombination fractions were estimated separately in females and males and were compared with values reported in the literature. A 1.33:1 ratio for the female:male recombination fraction was obtained by combining all sources, but the difference between the recombination fractions was not significantly different from zero. The present data, combined with those reported earlier, show that the most likely recombination fraction is about 14%.", "contents": "Evaluation of a possible sex difference in recombination for the ABO-AK linkage. Thirty-five informative families were scored for linkage between the ABO and AK loci. The recombination fractions were estimated separately in females and males and were compared with values reported in the literature. A 1.33:1 ratio for the female:male recombination fraction was obtained by combining all sources, but the difference between the recombination fractions was not significantly different from zero. The present data, combined with those reported earlier, show that the most likely recombination fraction is about 14%."} {"id": "PMID:173188", "title": "Determination of estrogens in pregnancy urine by hemoagglutination inhibition reaction.", "content": "A simple and rapid hemoagglutination inhibition reaction system for the estimation of estrogens in pregnancy urine is described. Results obtained by this method showed a good correlation with those measure by a conventional radioimmunoassay method and Brown's colorimetric method. Ninety-seven pregnancy urine samples from various gestational weeks were subjected to the assay, and the usefulness of this method as a screening test for high-risk pregnancy is discussed.", "contents": "Determination of estrogens in pregnancy urine by hemoagglutination inhibition reaction. A simple and rapid hemoagglutination inhibition reaction system for the estimation of estrogens in pregnancy urine is described. Results obtained by this method showed a good correlation with those measure by a conventional radioimmunoassay method and Brown's colorimetric method. Ninety-seven pregnancy urine samples from various gestational weeks were subjected to the assay, and the usefulness of this method as a screening test for high-risk pregnancy is discussed."} {"id": "PMID:173189", "title": "The ultrastructural response of human endometrium to medroxyprogesterone acetate.", "content": "Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.", "contents": "The ultrastructural response of human endometrium to medroxyprogesterone acetate. Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage."} {"id": "PMID:173190", "title": "Acute posterior multifocal placoid pigment epitheliopathy associated with an adenovirus type 5 infection.", "content": "A 19-year-old black man with acute posterior multifocal placoid pigment epitheliopathy had concurrent positive viral cultures and rising antibodies to adenovirus type 5. This finding, considered together with earlier reports of viral-like syndromes accompanying the disease, supports the implication of a respiratory virus as a possible etiologic factor.", "contents": "Acute posterior multifocal placoid pigment epitheliopathy associated with an adenovirus type 5 infection. A 19-year-old black man with acute posterior multifocal placoid pigment epitheliopathy had concurrent positive viral cultures and rising antibodies to adenovirus type 5. This finding, considered together with earlier reports of viral-like syndromes accompanying the disease, supports the implication of a respiratory virus as a possible etiologic factor."} {"id": "PMID:173192", "title": "Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol.", "content": "While glucocorticoid hormones act catabolically on skeletal muscle through their binding to glucocorticoid-specific receptors in the cytosol, androgens exert anabolic responses but no androgen-specific binding proteins could be detected in this responsive tissue. However, various nonradioactive androgens were effective in displacing labeled dexamethasone or cortisol from their respective cytoplasmic receptors in muscle, both in vitro and in vivo. The inhibition of glucocorticoid binding by androgens is competitive, and could be observed following a single or repeated administration of the androgens to adrenalectomized-castrated animals. The synthetic androgen fluoxymesterone and the hormone testosterone displayed Ki values of 7.5 X 10(-6) M and 1 X 10(-5) M, respectively, for the inhibition of [3H]dexamethasone binding in muscle cytosol. On the basis of competition experiments it is postulated that interaction of androgens with glucocorticoid receptors prevents the binding of glucocorticoids and might be responsible in part for the anabolic effects of pharmacologic doses of androgens in muscle.", "contents": "Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. While glucocorticoid hormones act catabolically on skeletal muscle through their binding to glucocorticoid-specific receptors in the cytosol, androgens exert anabolic responses but no androgen-specific binding proteins could be detected in this responsive tissue. However, various nonradioactive androgens were effective in displacing labeled dexamethasone or cortisol from their respective cytoplasmic receptors in muscle, both in vitro and in vivo. The inhibition of glucocorticoid binding by androgens is competitive, and could be observed following a single or repeated administration of the androgens to adrenalectomized-castrated animals. The synthetic androgen fluoxymesterone and the hormone testosterone displayed Ki values of 7.5 X 10(-6) M and 1 X 10(-5) M, respectively, for the inhibition of [3H]dexamethasone binding in muscle cytosol. On the basis of competition experiments it is postulated that interaction of androgens with glucocorticoid receptors prevents the binding of glucocorticoids and might be responsible in part for the anabolic effects of pharmacologic doses of androgens in muscle."} {"id": "PMID:173193", "title": "Renal cyclic AMP accumulation and adenulate cyclase stimulation by erythropoietic agents.", "content": "The regional distribution of cyclic AMP in the kidney was determined following erythropoietic stimulation with hypoxia and cobalt. Following these stimuli, increases in renal cyclic AMP concentrations were restricted to the cortex. The basis for this localization in the case of cobalt treatment was found to reside in the stimulation of renal cortical adenylate cyclase activity in vitro by concentrations of cobalt similar to those found in vivo. The level of cobalt in the cortex after cobalt treatment was found to approach 500 mumol/kg of tissue, whereas no detectable levels of cobalt were found in the renal medulla. Additionally, other agents such as parathyroid hormone and lactic acid, that are known to lack stimulatory effects on medullary adenylate cyclase, were found to stimulate the cortical enzyme. This stimulation of renal cortical adenylate cyclase correlates with enhanced erythropoiesis as demonstrated by increased radiolabeled iron incorporation into erythrocytes. These results support previous reports which suggest that renal cortical cyclic AMP mediates erythropoietin production in response to erythropoietically active agents.", "contents": "Renal cyclic AMP accumulation and adenulate cyclase stimulation by erythropoietic agents. The regional distribution of cyclic AMP in the kidney was determined following erythropoietic stimulation with hypoxia and cobalt. Following these stimuli, increases in renal cyclic AMP concentrations were restricted to the cortex. The basis for this localization in the case of cobalt treatment was found to reside in the stimulation of renal cortical adenylate cyclase activity in vitro by concentrations of cobalt similar to those found in vivo. The level of cobalt in the cortex after cobalt treatment was found to approach 500 mumol/kg of tissue, whereas no detectable levels of cobalt were found in the renal medulla. Additionally, other agents such as parathyroid hormone and lactic acid, that are known to lack stimulatory effects on medullary adenylate cyclase, were found to stimulate the cortical enzyme. This stimulation of renal cortical adenylate cyclase correlates with enhanced erythropoiesis as demonstrated by increased radiolabeled iron incorporation into erythrocytes. These results support previous reports which suggest that renal cortical cyclic AMP mediates erythropoietin production in response to erythropoietically active agents."} {"id": "PMID:173194", "title": "Alpha-Glycerol phosphatase and glycerol kinase activities in tissues of the silkmoth Hyalophora cecropia during the larval-pupal transformation.", "content": "Magnesium metabolism has been studied in Hyalophora cecropia during the larval-pupal transformation (LPT) (Jungreis, A. M., Am. J. Physiol. 224: 27--30, 1973). Throughout this period, it accumulated in midgut (0.5 M at ecdysis), presumably as osmotically inactive Mg3(PO4)2. Glycerol accumulation in hemolymph was also first noted during this period. Since total alpha-glycerol phosphate present in hemolymph declined between the larval and pupal stages of development, the relationship between magnesium and alpha-glycerol phosphate metabolism was studied. Specific and total alpha-glycerol phosphatase (degradative) and glycerol kinase (synthetic) enzyme activities were measured in fat-body and midgut tissue throughout the LPT. At both feeding larval and diapause pupal stages in development in both tissues, total glycerol kinase activity is greater than that of alpha-glycerol phosphatase with degradative/synthetic activity ratios of 0.2--0.5. In fat body, ratios remained constant or shifted in the direction of synthesis during the LPT, whereas those measured in midgut tissue increased in the direction of degradation with a maximum ratio of 5.8 noted following spinning. The increase in degradative/synthetic activity ratios in midgut tissue is attributed to a greater rate of loss of glycerol kinase than alpha-glycerol phosphatase enzyme activity. Orthophosphate, presumably released from alpha-glycerol phosphate within the cells of the pharate pupal midgut tissue, combines with magnesium to form osmotically inactive Mg3(PO4)2 crystals.", "contents": "Alpha-Glycerol phosphatase and glycerol kinase activities in tissues of the silkmoth Hyalophora cecropia during the larval-pupal transformation. Magnesium metabolism has been studied in Hyalophora cecropia during the larval-pupal transformation (LPT) (Jungreis, A. M., Am. J. Physiol. 224: 27--30, 1973). Throughout this period, it accumulated in midgut (0.5 M at ecdysis), presumably as osmotically inactive Mg3(PO4)2. Glycerol accumulation in hemolymph was also first noted during this period. Since total alpha-glycerol phosphate present in hemolymph declined between the larval and pupal stages of development, the relationship between magnesium and alpha-glycerol phosphate metabolism was studied. Specific and total alpha-glycerol phosphatase (degradative) and glycerol kinase (synthetic) enzyme activities were measured in fat-body and midgut tissue throughout the LPT. At both feeding larval and diapause pupal stages in development in both tissues, total glycerol kinase activity is greater than that of alpha-glycerol phosphatase with degradative/synthetic activity ratios of 0.2--0.5. In fat body, ratios remained constant or shifted in the direction of synthesis during the LPT, whereas those measured in midgut tissue increased in the direction of degradation with a maximum ratio of 5.8 noted following spinning. The increase in degradative/synthetic activity ratios in midgut tissue is attributed to a greater rate of loss of glycerol kinase than alpha-glycerol phosphatase enzyme activity. Orthophosphate, presumably released from alpha-glycerol phosphate within the cells of the pharate pupal midgut tissue, combines with magnesium to form osmotically inactive Mg3(PO4)2 crystals."} {"id": "PMID:173195", "title": "Corticosteroids and ACTH are not required for compensatory adrenal growth.", "content": "We have tested the hypothesis that unilateral adrenalectomy results in decreased glucocorticoid secretion, reflexly elevated ACTH secretion, and consequently, compensatory adrenal growth. Plasma ACTH and corticosterone and right adrenal weight were measured during the first 10 days after left adrenalectomy or sham adrenalectomy in young male rats. There is a decrease in plasma corticosterone after unilateral adrenalectomy compared to sham adrenalectomy that persists for 1 h. ACTH is elevated only at 2 h after unilateral adrenalectomy compared to shamoperated rats. Treatment with dexamethasone, shown to abolish the ACTH and corticosterone responses to laparotomy with intestinal traction, resulted in significantly increased adrenal weight after unilateral adrenalectomy by 6 h (wet or dry weight), and at 24 h. Compensatory adrenal growth also occurs after unilateral adrenalectomy in hypophysectomized rats (wet or dry weight). We conclude the compensatory adrenal growth after unilateral adrenalectomy requires neither a virtual decrease in circulating corticosterone levels nor elevated ACTH levels, and speculate that the phenomenon is neurally mediated.", "contents": "Corticosteroids and ACTH are not required for compensatory adrenal growth. We have tested the hypothesis that unilateral adrenalectomy results in decreased glucocorticoid secretion, reflexly elevated ACTH secretion, and consequently, compensatory adrenal growth. Plasma ACTH and corticosterone and right adrenal weight were measured during the first 10 days after left adrenalectomy or sham adrenalectomy in young male rats. There is a decrease in plasma corticosterone after unilateral adrenalectomy compared to sham adrenalectomy that persists for 1 h. ACTH is elevated only at 2 h after unilateral adrenalectomy compared to shamoperated rats. Treatment with dexamethasone, shown to abolish the ACTH and corticosterone responses to laparotomy with intestinal traction, resulted in significantly increased adrenal weight after unilateral adrenalectomy by 6 h (wet or dry weight), and at 24 h. Compensatory adrenal growth also occurs after unilateral adrenalectomy in hypophysectomized rats (wet or dry weight). We conclude the compensatory adrenal growth after unilateral adrenalectomy requires neither a virtual decrease in circulating corticosterone levels nor elevated ACTH levels, and speculate that the phenomenon is neurally mediated."} {"id": "PMID:173196", "title": "Minimal deviation hepatoma. A new entity.", "content": "The term minimal deviation hepatoma has been applied to a specific clinical, pathological, and angiographic entity. It is a tumor, composed of atypical cells, which is neither frankly malignant nor so well organized as a benigh tumor. This lesion occurs in females with otherwise normal livers and has a relatively benign course, although life threatening hemorrhage may occur. The diagnosis may be strongly suggested in the presence of hypervascularl or hypovascular discrete masses without evidence of frank malignancy, with a defect in the colloid liver scan and with normal liver function tests. Surgical resection when possible and aggressive chemotherapy may be corrective in many cases.", "contents": "Minimal deviation hepatoma. A new entity. The term minimal deviation hepatoma has been applied to a specific clinical, pathological, and angiographic entity. It is a tumor, composed of atypical cells, which is neither frankly malignant nor so well organized as a benigh tumor. This lesion occurs in females with otherwise normal livers and has a relatively benign course, although life threatening hemorrhage may occur. The diagnosis may be strongly suggested in the presence of hypervascularl or hypovascular discrete masses without evidence of frank malignancy, with a defect in the colloid liver scan and with normal liver function tests. Surgical resection when possible and aggressive chemotherapy may be corrective in many cases."} {"id": "PMID:173197", "title": "Percutaneous transhepatic cholangiography. Problems in interpretation.", "content": "The patient who presents with jaundice, regardless of the etiology, cannot be adequately examined by a gallbladder series and intravenous cholangiography. Clinical evaluation aided by laboratory analysis will not always differentiate between primary liver parenchymal disease and biliary tract obstruction. Percutaneous transhepatic cholangiography, when successfully performed, answers the question of whether the jaundice is due to primary liver parenchymal disease or due to biliary tract obstruction. The point to emphasize is that under no circumstances is it appropriate to presume any information if the biliary system is not entered and visualized successfully. The proper interpretation of the level of block can fall prey to the mistake of incomplete aspiration of the thick, inspissated bile in the obstructed biliary tree before injection of contrast material. The problem will be worsened by a peripheral entrance into the biliary system rather than a more central one. Gastrointestinal series should always be available to aid in identifying pathology at the entrace of the common bile duct into the duodenum. Lastly, identifying the etiology at the site of the block will require additional procedures. Selective visceral angiography has contributed greatly in this area. During the 20 years of clinical usage of percutaneous transhepatic cholangiography, we feel it has become the single examination capable of preventing unnecessary exploration of the jaundiced patient with primary liver parenchymal disease and the most useful potential source of practical information if laparotomy is necessary to correct biliary tract obstruction.", "contents": "Percutaneous transhepatic cholangiography. Problems in interpretation. The patient who presents with jaundice, regardless of the etiology, cannot be adequately examined by a gallbladder series and intravenous cholangiography. Clinical evaluation aided by laboratory analysis will not always differentiate between primary liver parenchymal disease and biliary tract obstruction. Percutaneous transhepatic cholangiography, when successfully performed, answers the question of whether the jaundice is due to primary liver parenchymal disease or due to biliary tract obstruction. The point to emphasize is that under no circumstances is it appropriate to presume any information if the biliary system is not entered and visualized successfully. The proper interpretation of the level of block can fall prey to the mistake of incomplete aspiration of the thick, inspissated bile in the obstructed biliary tree before injection of contrast material. The problem will be worsened by a peripheral entrance into the biliary system rather than a more central one. Gastrointestinal series should always be available to aid in identifying pathology at the entrace of the common bile duct into the duodenum. Lastly, identifying the etiology at the site of the block will require additional procedures. Selective visceral angiography has contributed greatly in this area. During the 20 years of clinical usage of percutaneous transhepatic cholangiography, we feel it has become the single examination capable of preventing unnecessary exploration of the jaundiced patient with primary liver parenchymal disease and the most useful potential source of practical information if laparotomy is necessary to correct biliary tract obstruction."} {"id": "PMID:173198", "title": "Hepatic echography.", "content": "There are 2 kinds of echographic investigations: those which are only complementary and those which are specific by themselves. To improve this latter category, we would like to emphasize two useful echographic signs. First, the attenuation sign, which indicates the fibrotic nature, therefore practically speaking, the cirrhotic nature of a diffuse echogenic pattern. Secondly, the posterior echo accumulation sign, which indicates the liquid nature, and therefore in general the cystic nature of a localized sonolucent pattern.", "contents": "Hepatic echography. There are 2 kinds of echographic investigations: those which are only complementary and those which are specific by themselves. To improve this latter category, we would like to emphasize two useful echographic signs. First, the attenuation sign, which indicates the fibrotic nature, therefore practically speaking, the cirrhotic nature of a diffuse echogenic pattern. Secondly, the posterior echo accumulation sign, which indicates the liquid nature, and therefore in general the cystic nature of a localized sonolucent pattern."} {"id": "PMID:173199", "title": "Compensatory renal hypertrophy after treatment for Wilms' tumor.", "content": "In children who undergo nephrectomy for Wilms' tumor, compensatory renal hypertrophy occurs rapidly despite concomitant irradiation and chemotherapy. Review of preoperative and postoperative intravenous pyelograms of 21 children showed all to have significant enlargement of the remaining kidney. Sixty-five per cent renal hypertrophy occurred during the first 2 months after nephrectomy; by 11 months, renal hypertrophy is complete and renal growth is no longer accelerated.", "contents": "Compensatory renal hypertrophy after treatment for Wilms' tumor. In children who undergo nephrectomy for Wilms' tumor, compensatory renal hypertrophy occurs rapidly despite concomitant irradiation and chemotherapy. Review of preoperative and postoperative intravenous pyelograms of 21 children showed all to have significant enlargement of the remaining kidney. Sixty-five per cent renal hypertrophy occurred during the first 2 months after nephrectomy; by 11 months, renal hypertrophy is complete and renal growth is no longer accelerated."} {"id": "PMID:173206", "title": "A new concept in the measurement of neuromuscular transmission and block.", "content": "The discovery of the safety margin of neuromuscular transmission has brought forth the requirement for an improvement in the clinical examination of curarization, since the safety margin, i.e. the reserves, should also be measured. For this purpose a peripheral nerve stimulator and an electromechanical recorder unit have been produced, suitable for both the examination of manifest curarization and of the neuromuscular reserves. The measurements of muscle relaxation are performed making use of 30 Hz stimulation, while the safety margin of neuromuscular transmission is measured using stimulation at 200 Hz one.", "contents": "A new concept in the measurement of neuromuscular transmission and block. The discovery of the safety margin of neuromuscular transmission has brought forth the requirement for an improvement in the clinical examination of curarization, since the safety margin, i.e. the reserves, should also be measured. For this purpose a peripheral nerve stimulator and an electromechanical recorder unit have been produced, suitable for both the examination of manifest curarization and of the neuromuscular reserves. The measurements of muscle relaxation are performed making use of 30 Hz stimulation, while the safety margin of neuromuscular transmission is measured using stimulation at 200 Hz one."} {"id": "PMID:173210", "title": "Equine serum lipids: serum lipoprotein profiles of Morgan and Thoroughbred horses.", "content": "The serum of lipoproteins of 10 Morgan and 8 Thoroughbred horses were examined by 2 methods of polyacrylamide gel electrophoresis. A significant breed difference in the beta-lipoprotein to alpha-lipoprotein ratio was seen in gradient slab electrophoresis. A breed difference in the number of peaks, but no difference in beta-lipoprotein to alpha-lipoprotein ratio, was found in disc gel electrophoresis. These results have been correlated to indicate differences in charge of alpha-lipoprotein components and in size of beta-lipoprotein components between these 2 breeds of horses.", "contents": "Equine serum lipids: serum lipoprotein profiles of Morgan and Thoroughbred horses. The serum of lipoproteins of 10 Morgan and 8 Thoroughbred horses were examined by 2 methods of polyacrylamide gel electrophoresis. A significant breed difference in the beta-lipoprotein to alpha-lipoprotein ratio was seen in gradient slab electrophoresis. A breed difference in the number of peaks, but no difference in beta-lipoprotein to alpha-lipoprotein ratio, was found in disc gel electrophoresis. These results have been correlated to indicate differences in charge of alpha-lipoprotein components and in size of beta-lipoprotein components between these 2 breeds of horses."} {"id": "PMID:173211", "title": "Equine serum lipids: lipid composition and electrophoretic mobility of equine serum lipoprotein fractions.", "content": "The serum lipoprotein fractions from 5 Morgan and 5 Thoroughbred horses were isolated by preparative ultracentrifugation, chemically analyzed for lipid composition, and studied by 2 methods of polyacrylamide gel electrophoresis to determine electrophoretic mobility. Breed differences were not seen in the relative percentages of the lipid classes found in the various fractions. Normally, horses, like most animals, carry the majority of their lipid in high-density lipoproteins. Electrophoretically, the only difference seen between breeds occurred on disc electrophoresis where the extra band, which is characteristic of lipoprotein profiles of Morgans, was found in the high-density lipoprotein fraction.", "contents": "Equine serum lipids: lipid composition and electrophoretic mobility of equine serum lipoprotein fractions. The serum lipoprotein fractions from 5 Morgan and 5 Thoroughbred horses were isolated by preparative ultracentrifugation, chemically analyzed for lipid composition, and studied by 2 methods of polyacrylamide gel electrophoresis to determine electrophoretic mobility. Breed differences were not seen in the relative percentages of the lipid classes found in the various fractions. Normally, horses, like most animals, carry the majority of their lipid in high-density lipoproteins. Electrophoretically, the only difference seen between breeds occurred on disc electrophoresis where the extra band, which is characteristic of lipoprotein profiles of Morgans, was found in the high-density lipoprotein fraction."} {"id": "PMID:173212", "title": "Pathogenicity of a caprine herpesvirus.", "content": "A herpesvirus isolated from neonatal Angora kids (Capra hircus) with a relatively severe generalized infection was shown to be infective for adult goats as well as for kids. However, the virus lacked pathogenicity for either lambs or calves. Although a nonreciprocating serologic overlap exists between the caprine virus and the antibody to bovine herpesvirus (BHV-1), results of cross immunity tests in calves indicated that the 2 viruses are immunologically distinct. On the basis of these findings, the caprine virus seems to be a specific pathogen of goats. Accordingly, the designation of Herpesvirus caprae or caprine herpesvirus 1 seems taxonomically appropriate.", "contents": "Pathogenicity of a caprine herpesvirus. A herpesvirus isolated from neonatal Angora kids (Capra hircus) with a relatively severe generalized infection was shown to be infective for adult goats as well as for kids. However, the virus lacked pathogenicity for either lambs or calves. Although a nonreciprocating serologic overlap exists between the caprine virus and the antibody to bovine herpesvirus (BHV-1), results of cross immunity tests in calves indicated that the 2 viruses are immunologically distinct. On the basis of these findings, the caprine virus seems to be a specific pathogen of goats. Accordingly, the designation of Herpesvirus caprae or caprine herpesvirus 1 seems taxonomically appropriate."} {"id": "PMID:173209", "title": "[Peripheral neuropathies i- Waldenstrom's disease. Histological and ultrastructural studies of 5 cases].", "content": "In four cases it was the existence of peripheral neuropathy which led to the discovery of macroglobulinemia within an interval from 1 to 11 years. The treatment of the disease also markedly improved the peripheral neuropathy in three cases. Two patients died. Two of the biopsies of the peripheral nerve showed infiltration by atypical lymphocytes. Ultrastructural changes in the five cases were variable. Marked axonal involvement in the two cases with cellular infiltration. In one of these two cases it was combined with segmental demyelinization. This lesion was clearly predominant in the three other cases. In one of them demyelinization occurred in a very peculiar way with dilation of the internal part of the mesaxone going on in the most peripheral layers of the myelin. Discussion of the mechanisms of the involvement of the peripheral nervous parenchyma in Waldenstr\u00f6m's disease. Cellular infiltrations, amorphous deposits, changes in the capillaries and macroglobuline may occur.", "contents": "[Peripheral neuropathies i- Waldenstrom's disease. Histological and ultrastructural studies of 5 cases]. In four cases it was the existence of peripheral neuropathy which led to the discovery of macroglobulinemia within an interval from 1 to 11 years. The treatment of the disease also markedly improved the peripheral neuropathy in three cases. Two patients died. Two of the biopsies of the peripheral nerve showed infiltration by atypical lymphocytes. Ultrastructural changes in the five cases were variable. Marked axonal involvement in the two cases with cellular infiltration. In one of these two cases it was combined with segmental demyelinization. This lesion was clearly predominant in the three other cases. In one of them demyelinization occurred in a very peculiar way with dilation of the internal part of the mesaxone going on in the most peripheral layers of the myelin. Discussion of the mechanisms of the involvement of the peripheral nervous parenchyma in Waldenstr\u00f6m's disease. Cellular infiltrations, amorphous deposits, changes in the capillaries and macroglobuline may occur."} {"id": "PMID:173213", "title": "Synthesis of fibroma viral deoxyribonucleic acid complexes in rabbit kidney cells.", "content": "Cytoplasmic extracts of primary rabbit kidney cells inoculated with fibroma virus revealed 2 peaks of DNA complexes (120S and greater than or equal to 410S) in a linear sucrose gradient. Pulse-chase experiments demonstrated a shift in the gradient profile of lighter complexes toward heavier complexes. Synthesis of DNA complexes was inhibited by adding puromycin or actinomycin D. The DNA from virus-infected cultures hybridized 7 to 9 times greater with fibroma virus DNA than did the DNA from noninfected cultuures. The DNA complexes became increasingly resistant to deoxyribonuclease digestion as a function of time during viral growth cycle and produced tumors in rabbits.", "contents": "Synthesis of fibroma viral deoxyribonucleic acid complexes in rabbit kidney cells. Cytoplasmic extracts of primary rabbit kidney cells inoculated with fibroma virus revealed 2 peaks of DNA complexes (120S and greater than or equal to 410S) in a linear sucrose gradient. Pulse-chase experiments demonstrated a shift in the gradient profile of lighter complexes toward heavier complexes. Synthesis of DNA complexes was inhibited by adding puromycin or actinomycin D. The DNA from virus-infected cultures hybridized 7 to 9 times greater with fibroma virus DNA than did the DNA from noninfected cultuures. The DNA complexes became increasingly resistant to deoxyribonuclease digestion as a function of time during viral growth cycle and produced tumors in rabbits."} {"id": "PMID:173215", "title": "Angiographic assessment of resectability in primary hepatic carcinoma.", "content": "The nature of primary hepatic malignancy and the magnitude of operative procedures for treatment dictate that hepatic resection be carried out only when there is the chance of cure. Following resection, a sufficient amount of liver with an intact afferent and efferent vascular system must remain to sustain life. Complete hepatic angiographic evaluation by arteriography, inferior vena cavography, hepatic venography and portal venography provides valuable information about extent of tumor involvement and the anticipated hepatic remnant. Complete preoperative knowledge of hepatic vascular anatomy should permit better selection of patients for potentially curative resection and avoid operation in patients with incurable tumors.", "contents": "Angiographic assessment of resectability in primary hepatic carcinoma. The nature of primary hepatic malignancy and the magnitude of operative procedures for treatment dictate that hepatic resection be carried out only when there is the chance of cure. Following resection, a sufficient amount of liver with an intact afferent and efferent vascular system must remain to sustain life. Complete hepatic angiographic evaluation by arteriography, inferior vena cavography, hepatic venography and portal venography provides valuable information about extent of tumor involvement and the anticipated hepatic remnant. Complete preoperative knowledge of hepatic vascular anatomy should permit better selection of patients for potentially curative resection and avoid operation in patients with incurable tumors."} {"id": "PMID:173216", "title": "Diagnostic error in breast disease.", "content": "Fifty-six breast biopsies, incorrectly assessed by preoperative clinical or mammographic examination, were reviewed to define the characteristics in the tumor or patient that caused the clinician and mammographer to be diagnostically inaccurate. The most important patient characteristic associated with error was the use of hormones. Failure to recognize that oral contraceptive use significantly reduces the incidience of benign breast disease contributed to the frequent misdiagnosis of lesions in those patients. Twelve of 16 masses in oral contraceptive users were malignant. In seven, their resemblance to cysts or fibroadenomas resulted in treatment delay of two weeks or 18 months. Because benign disease is uncommon in women who have used contraceptives two or more years, all new lesions in those women should be studied by biopsy promptly. Neither clinical nor mammographic evaluation of lesions in postmenopausal women who used estrogens was accurate. Twelve postmenopausal patients with carcinoma had used estrogens. Three of these lesions were considered benign clinically and four, by mammogram. In one, treatment was delayed four years. In women over 50 not using hormones, clinical diagnosis of malignancy was accurate. Ten carcinomas in those women were missed by mammogram. Eight had negative nodes; thus a negative mamogram when the clinical diagnosis is correct may be an effective guide in predicting the status of axillary nodes. Paget's disease was not recognized clinically in two of eight patients with that disease, and an additional two were not recognized on mammography. The initial examiner did not identify three of six inflammatory carcinomas. Ten percent of benign lesions were intraductal hyperplasia or papillomatosis with atypia and were the benign lesions most often misdiagnosed clinically and by mammogram. No microscopic lesions were noted on mammography without an associated palpable mass. Twenty-five per cent of the lesions in women aged 40-49 were incorrectly assessed by mammography or clinical examination. Four (15%) of the 27 carcinomas in this age group were not recognized by either modality. Mammography helped delineate the characteristics of masses in premenopausal women. With recognition that any mass that appears in a woman using oral contraceptives must be studied by biopsy, combined clinical and mammographic study in primenopausal women should minimize diagnostic error. Unfortunately, neither clinical nor mammographic evaluation of the women with irregular periods approaching menopause or within three years past menopause is accurate. It is in that age group that new diagnostic modalities are needed and when reported their efficacy in that age group should be stressed.", "contents": "Diagnostic error in breast disease. Fifty-six breast biopsies, incorrectly assessed by preoperative clinical or mammographic examination, were reviewed to define the characteristics in the tumor or patient that caused the clinician and mammographer to be diagnostically inaccurate. The most important patient characteristic associated with error was the use of hormones. Failure to recognize that oral contraceptive use significantly reduces the incidience of benign breast disease contributed to the frequent misdiagnosis of lesions in those patients. Twelve of 16 masses in oral contraceptive users were malignant. In seven, their resemblance to cysts or fibroadenomas resulted in treatment delay of two weeks or 18 months. Because benign disease is uncommon in women who have used contraceptives two or more years, all new lesions in those women should be studied by biopsy promptly. Neither clinical nor mammographic evaluation of lesions in postmenopausal women who used estrogens was accurate. Twelve postmenopausal patients with carcinoma had used estrogens. Three of these lesions were considered benign clinically and four, by mammogram. In one, treatment was delayed four years. In women over 50 not using hormones, clinical diagnosis of malignancy was accurate. Ten carcinomas in those women were missed by mammogram. Eight had negative nodes; thus a negative mamogram when the clinical diagnosis is correct may be an effective guide in predicting the status of axillary nodes. Paget's disease was not recognized clinically in two of eight patients with that disease, and an additional two were not recognized on mammography. The initial examiner did not identify three of six inflammatory carcinomas. Ten percent of benign lesions were intraductal hyperplasia or papillomatosis with atypia and were the benign lesions most often misdiagnosed clinically and by mammogram. No microscopic lesions were noted on mammography without an associated palpable mass. Twenty-five per cent of the lesions in women aged 40-49 were incorrectly assessed by mammography or clinical examination. Four (15%) of the 27 carcinomas in this age group were not recognized by either modality. Mammography helped delineate the characteristics of masses in premenopausal women. With recognition that any mass that appears in a woman using oral contraceptives must be studied by biopsy, combined clinical and mammographic study in primenopausal women should minimize diagnostic error. Unfortunately, neither clinical nor mammographic evaluation of the women with irregular periods approaching menopause or within three years past menopause is accurate. It is in that age group that new diagnostic modalities are needed and when reported their efficacy in that age group should be stressed."} {"id": "PMID:173217", "title": "Foodhandler-associated outbreak of hepatitis type A. An immune electron microscopic study.", "content": "Immune electron microscopy, which can detect hepatitis A antigen and antibody (anti-HA), was used to study a foodhandler-associated outbreak of hepatitis among 136 naval recruits. In stool specimens collected during the acute phase of illness, 27-nm viruslike hapatitis A antigen particles were shown, but only in patients with icteric hepatitis. Detection was possible in stools collected as early as 10 days before peak serum aminotransferase activity and up to the time of peak enzyme activity, but not thereafter. The immunologic similarity of these viruslike particles to those found in acute phase stools of volunteers inoculated with the MS-1 strain of hepatitis A virus was determined, and an increase in anti-HA was shown between acute and convalescent serums from 25 of the recruits. These data support the view that the MS-1 strain of hepatitis A virus is serologically related to naturally acquired type A hepatitis.", "contents": "Foodhandler-associated outbreak of hepatitis type A. An immune electron microscopic study. Immune electron microscopy, which can detect hepatitis A antigen and antibody (anti-HA), was used to study a foodhandler-associated outbreak of hepatitis among 136 naval recruits. In stool specimens collected during the acute phase of illness, 27-nm viruslike hapatitis A antigen particles were shown, but only in patients with icteric hepatitis. Detection was possible in stools collected as early as 10 days before peak serum aminotransferase activity and up to the time of peak enzyme activity, but not thereafter. The immunologic similarity of these viruslike particles to those found in acute phase stools of volunteers inoculated with the MS-1 strain of hepatitis A virus was determined, and an increase in anti-HA was shown between acute and convalescent serums from 25 of the recruits. These data support the view that the MS-1 strain of hepatitis A virus is serologically related to naturally acquired type A hepatitis."} {"id": "PMID:173218", "title": "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion.", "content": "We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.", "contents": "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion."} {"id": "PMID:173221", "title": "Islet cell carcinoma, pancreatic cholera, and vasoactive intestinal peptide.", "content": "Three patients with profuse diarrhea, hypokalemia, metastatic nonbeta islet cell carcinoma, and the absence of gastric hypersecretion were found to have elevated levels of vasoactive intestinal peptide. One patient also had elevated serum gastrin levels. Two patients experienced prolonged remissions of diarrhea after operations in which only tumor biopsies were done. These cases further implicate vasoactive intestinal peptide as the agent mediating the diarrhea in the syndrome of pancreatic cholera.", "contents": "Islet cell carcinoma, pancreatic cholera, and vasoactive intestinal peptide. Three patients with profuse diarrhea, hypokalemia, metastatic nonbeta islet cell carcinoma, and the absence of gastric hypersecretion were found to have elevated levels of vasoactive intestinal peptide. One patient also had elevated serum gastrin levels. Two patients experienced prolonged remissions of diarrhea after operations in which only tumor biopsies were done. These cases further implicate vasoactive intestinal peptide as the agent mediating the diarrhea in the syndrome of pancreatic cholera."} {"id": "PMID:173223", "title": "[Studies on the conidial differentiation of \"Neurospora crassa\" VI.--Functional anomalies of the conditional aconidial mutant \"amycelial\" (author's transl)].", "content": "Studies using the morphological mutant \"amycelial\"--a conditional, aconidial strain of N. crassa--have revealed certain consistent functional and biochemical differences from wild type strains showing normal morphology and conidia formation. Thus it was found that the mutant strain showed an abnormal utilization of protein reserves at a time when there is extensive degradation during conidiogenesis in wild type. In addition, the mutant exhibited abnormally low oxygen consumption and free amino acid pools depressed nearly 3/4 with respect to wild type. All of these findings are consistent with earlier work linking conidiogenesis to aerobic oxidative processes and suggest that catabolic reactions particularly regarding protein breakdown may be important to conidiogenesis from the standpoint of the synthesis of new conidial proteins and for the supply of endogenous energy reserves during the process. The aconidial character of \"amycelial\" could be partially alleviated on solid acetate medium supplemented with amino acids, especially tryptophan or histidine. Conidiation was also induced by cyclic-AMP, even on sucrose medium. A polymer strongly antigenic in rabbits was found to be released into growth medium by the mutant but not by wild type cultures, providing a possible clue to the immediate cause of the abnormal morphology seen in \"amycelial\". This substance appears to be a glycopeptide containing a few hexoses and amino acids associated with polyphosphate.", "contents": "[Studies on the conidial differentiation of \"Neurospora crassa\" VI.--Functional anomalies of the conditional aconidial mutant \"amycelial\" (author's transl)]. Studies using the morphological mutant \"amycelial\"--a conditional, aconidial strain of N. crassa--have revealed certain consistent functional and biochemical differences from wild type strains showing normal morphology and conidia formation. Thus it was found that the mutant strain showed an abnormal utilization of protein reserves at a time when there is extensive degradation during conidiogenesis in wild type. In addition, the mutant exhibited abnormally low oxygen consumption and free amino acid pools depressed nearly 3/4 with respect to wild type. All of these findings are consistent with earlier work linking conidiogenesis to aerobic oxidative processes and suggest that catabolic reactions particularly regarding protein breakdown may be important to conidiogenesis from the standpoint of the synthesis of new conidial proteins and for the supply of endogenous energy reserves during the process. The aconidial character of \"amycelial\" could be partially alleviated on solid acetate medium supplemented with amino acids, especially tryptophan or histidine. Conidiation was also induced by cyclic-AMP, even on sucrose medium. A polymer strongly antigenic in rabbits was found to be released into growth medium by the mutant but not by wild type cultures, providing a possible clue to the immediate cause of the abnormal morphology seen in \"amycelial\". This substance appears to be a glycopeptide containing a few hexoses and amino acids associated with polyphosphate."} {"id": "PMID:173227", "title": "Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells.", "content": "Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids.", "contents": "Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells. Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids."} {"id": "PMID:173228", "title": "Immunodeficiency to hepatitis B virus infection and genetic susceptibility to development of hepatocellular carcinoma.", "content": "The high frequency of hepatitis B antigen (HBsAg) in hepatocellular carcinoma (HCC) patients has led to the hypothesis that immunoresponsiveness to hepatitis B virus (HBV) may be deficient in some patients, and that the immune response deficiency may have a genetic basis. Radioelectrocomplexing (REC), a radioimmunoassay in gel based on the principle of counterimmunoelectrophoresis (CIE), has been used to identify four HBV immune status subgroups: 1) HBsAg +ve/HBsAb +ve; 2) HBsAg +ve/HBsAb -ve; 3) HBsAb -ve/HBsAb +ve; 4) HBsAg -ve/HBsAb -ve/HBsAb -ve. These subgroups comprise 2, 6, 70, and 22 percent, respectively, among blood donors, and 32, 19, 23, and 26 percent, respectively, among HCC patients. Although the HBV exposure rates in the two groups were similar, the immune complexemic rates and HBs antigenemic rates were significantly higher in HBB patients than in the blood donors. It is proposed that the failure of termination of HBV infection revealed by these high rates reflects an immunodeficiency state characterized by an inability to produce high-avidity HBsAb. The immunodeficiency might have a primary genetic basis, or it might be secondary to the immunodepressive effects of concurrent viral or parasitic infections.", "contents": "Immunodeficiency to hepatitis B virus infection and genetic susceptibility to development of hepatocellular carcinoma. The high frequency of hepatitis B antigen (HBsAg) in hepatocellular carcinoma (HCC) patients has led to the hypothesis that immunoresponsiveness to hepatitis B virus (HBV) may be deficient in some patients, and that the immune response deficiency may have a genetic basis. Radioelectrocomplexing (REC), a radioimmunoassay in gel based on the principle of counterimmunoelectrophoresis (CIE), has been used to identify four HBV immune status subgroups: 1) HBsAg +ve/HBsAb +ve; 2) HBsAg +ve/HBsAb -ve; 3) HBsAb -ve/HBsAb +ve; 4) HBsAg -ve/HBsAb -ve/HBsAb -ve. These subgroups comprise 2, 6, 70, and 22 percent, respectively, among blood donors, and 32, 19, 23, and 26 percent, respectively, among HCC patients. Although the HBV exposure rates in the two groups were similar, the immune complexemic rates and HBs antigenemic rates were significantly higher in HBB patients than in the blood donors. It is proposed that the failure of termination of HBV infection revealed by these high rates reflects an immunodeficiency state characterized by an inability to produce high-avidity HBsAb. The immunodeficiency might have a primary genetic basis, or it might be secondary to the immunodepressive effects of concurrent viral or parasitic infections."} {"id": "PMID:173229", "title": "Carcinofetal alterations in glycogen phosphorylase isozymes in rat hepatomas.", "content": "As part of a continuing study on the loss or retention of enzymes involved in specific hepatic functions in a series of rat liver neoplasms ranging widely in growth rate and degree of differentiation, isozyme patterns of glycogen phosphorylase in rat hepatomas were compared with those in rat tissues during development. A third phosphorylase isozyme, distinguishable kinetically, immunologically, electrophoretically, and by isoelectric focusing from liver and muscle types is commonly present in various rat hepatomas including Novikoff, Morris, and Yoshida hepatomas with various degrees of retention of liver type according to their degree of differentiation. This isozyme is also the sole type in the placenta and early embryo, and in liver and muscle is replaced with the organ specific liver and muscle types during development. In other organs, the replacement is only partial, and, especially in adult rat brain, this type is retained. Thus, this isozyme seems to be a prototype whose appearance in hepatomas is one of many examples of carcinofetal alterations in isozymes.", "contents": "Carcinofetal alterations in glycogen phosphorylase isozymes in rat hepatomas. As part of a continuing study on the loss or retention of enzymes involved in specific hepatic functions in a series of rat liver neoplasms ranging widely in growth rate and degree of differentiation, isozyme patterns of glycogen phosphorylase in rat hepatomas were compared with those in rat tissues during development. A third phosphorylase isozyme, distinguishable kinetically, immunologically, electrophoretically, and by isoelectric focusing from liver and muscle types is commonly present in various rat hepatomas including Novikoff, Morris, and Yoshida hepatomas with various degrees of retention of liver type according to their degree of differentiation. This isozyme is also the sole type in the placenta and early embryo, and in liver and muscle is replaced with the organ specific liver and muscle types during development. In other organs, the replacement is only partial, and, especially in adult rat brain, this type is retained. Thus, this isozyme seems to be a prototype whose appearance in hepatomas is one of many examples of carcinofetal alterations in isozymes."} {"id": "PMID:173234", "title": "Preoperative embolization of juvenile angiofibromas of the nasopharynx.", "content": "The juvenile nasopharyngeal angiofibroma is a vascular tumor. Careful and complete removal is challenging because of the brisk bleeding during surgery. The means applied to reduce this blood loss have included preoperative estrogens, ligation of feeding vessels, silicone embolization of feeding vessels, and cryosurgery. We have used preoperative Gelfoam embolization of the internal maxillary artery in seven patients. Our clinical impression of significant reduction in loss of blood was confirmed by comparison with 16 previous patients. The average amount of blood lost in the embolized group was half that of the control group. A study of this type comprises many variables; however, the results do suggest that preoperative embolization of the internal maxillary artery is of advantage in the surgical treatment of juvenile angiofibromas.", "contents": "Preoperative embolization of juvenile angiofibromas of the nasopharynx. The juvenile nasopharyngeal angiofibroma is a vascular tumor. Careful and complete removal is challenging because of the brisk bleeding during surgery. The means applied to reduce this blood loss have included preoperative estrogens, ligation of feeding vessels, silicone embolization of feeding vessels, and cryosurgery. We have used preoperative Gelfoam embolization of the internal maxillary artery in seven patients. Our clinical impression of significant reduction in loss of blood was confirmed by comparison with 16 previous patients. The average amount of blood lost in the embolized group was half that of the control group. A study of this type comprises many variables; however, the results do suggest that preoperative embolization of the internal maxillary artery is of advantage in the surgical treatment of juvenile angiofibromas."} {"id": "PMID:173238", "title": "Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria.", "content": "The sensitivity of three strains of anaerobic intestinal bacteria, Clostridium perfringens, Bacteroides fragilis, and Peptococcus magnus, to the differential effects of oxygen and adverse oxidation-reduction potential was measured. The multiplication of the three organisms was inhibited in the presence of oxygen whether the medium was at a negative oxidation-reduction potential (Eh of -50 mV), poised by the intermittent addition of dithiothreitol, or at a positive oxidation-reduction potential (Eh of near +500 mV). However, when these organisms were cultured in the presence of oxygen, no inhibition was observed, even when the oxidation-reduction potential was maintained at an average Eh of +325 mV by the addition of potassium ferricyanide. When the cultures were aerated, the growth patterns of the three organisms demonstrated different sensitivities to oxygen. P. magnus was found to be the most sensitive. After 2 h of aerobic incubation, no viable organisms could be detected. B. fragilis was intermediately sensitive to oxygen with no viable organisms detected after 5 h of aerobic incubation. C. perfringens was the least sensitive. Under conditions of aerobic incubation, viable organisms survived for 10 h. During the experiments with Clostridium, no spores were observed by spore staining.", "contents": "Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. The sensitivity of three strains of anaerobic intestinal bacteria, Clostridium perfringens, Bacteroides fragilis, and Peptococcus magnus, to the differential effects of oxygen and adverse oxidation-reduction potential was measured. The multiplication of the three organisms was inhibited in the presence of oxygen whether the medium was at a negative oxidation-reduction potential (Eh of -50 mV), poised by the intermittent addition of dithiothreitol, or at a positive oxidation-reduction potential (Eh of near +500 mV). However, when these organisms were cultured in the presence of oxygen, no inhibition was observed, even when the oxidation-reduction potential was maintained at an average Eh of +325 mV by the addition of potassium ferricyanide. When the cultures were aerated, the growth patterns of the three organisms demonstrated different sensitivities to oxygen. P. magnus was found to be the most sensitive. After 2 h of aerobic incubation, no viable organisms could be detected. B. fragilis was intermediately sensitive to oxygen with no viable organisms detected after 5 h of aerobic incubation. C. perfringens was the least sensitive. Under conditions of aerobic incubation, viable organisms survived for 10 h. During the experiments with Clostridium, no spores were observed by spore staining."} {"id": "PMID:173235", "title": "Carcinoma of the nasopharynx in children.", "content": "Seven children with carcinoma of the nasopharynx have been treated and followed for five years. In this group of patients there were no cranial nerve palsies or radiographic evidence of destruction of the base of the skull. Four of the seven patients are living and well. The development of lymphoepithelioma in two siblings is of great interest from an environmental and genetic point of view. The older sibling developed the clinical manifestations of the tumor at 12 years of age and four years later the younger sibling developed them at 14 years of age. The possible etiologic relationship of carcinoma of the nasopharynx to the Epstein-Barr virus is discussed. The good survival rate in these patients under 21 years of age suggests that the prognosis in carcinoma of the nasopharynx is better in the younger age group than in adults. The management of these patients illustrates that carcinoma of the nasopharynx should be managed as a regional rather than a systemic disease. Systemic drug therapy is sometimes advocated because of confusion over the name lymphoepithelioma on the assumption that these tumors are more related to lymphomas and lymphosarcomas than carcinomas. It is clear that lymphoepitheliomas should be managed as carcinomas.", "contents": "Carcinoma of the nasopharynx in children. Seven children with carcinoma of the nasopharynx have been treated and followed for five years. In this group of patients there were no cranial nerve palsies or radiographic evidence of destruction of the base of the skull. Four of the seven patients are living and well. The development of lymphoepithelioma in two siblings is of great interest from an environmental and genetic point of view. The older sibling developed the clinical manifestations of the tumor at 12 years of age and four years later the younger sibling developed them at 14 years of age. The possible etiologic relationship of carcinoma of the nasopharynx to the Epstein-Barr virus is discussed. The good survival rate in these patients under 21 years of age suggests that the prognosis in carcinoma of the nasopharynx is better in the younger age group than in adults. The management of these patients illustrates that carcinoma of the nasopharynx should be managed as a regional rather than a systemic disease. Systemic drug therapy is sometimes advocated because of confusion over the name lymphoepithelioma on the assumption that these tumors are more related to lymphomas and lymphosarcomas than carcinomas. It is clear that lymphoepitheliomas should be managed as carcinomas."} {"id": "PMID:173239", "title": "Inhibitor of Clostridium perfringens formed by heating sodium nitrite in a chemically defined medium.", "content": "An inhibitor of Clostridium perfringens formed when low levels of nitrite were autoclaved with a defined chemical medium. A systematic study of the medium revealed that only amino acids and mineral salts were involved in the production of this inhibitor, which was proven to be a toxic compound formed from cysteine, ferrous sulfate, and sodium nitrite. The inhibitor was compared to several known compounds. S-nitrosocysteine inhibited the test organism, but would not form in the test system in amounts large enough to explain the observed inhibition. Roussin red salt was unstable in the test system and therefore was not the inhibitor. Roussin black salt, which was also inhibitory, could form in sufficient amounts to explain the inhibition. A complex of cysteine, iron, and nitric oxide was detected in the autoclaved solution of cysteine, ferrous sulfate, and sodium nitrite; this cysteine complex did not appear to be inhibitory, however, at levels which could form in the autoclaved medium. The observed inhibition may have been due to the combined effects of sublethal concentrations of each compound.", "contents": "Inhibitor of Clostridium perfringens formed by heating sodium nitrite in a chemically defined medium. An inhibitor of Clostridium perfringens formed when low levels of nitrite were autoclaved with a defined chemical medium. A systematic study of the medium revealed that only amino acids and mineral salts were involved in the production of this inhibitor, which was proven to be a toxic compound formed from cysteine, ferrous sulfate, and sodium nitrite. The inhibitor was compared to several known compounds. S-nitrosocysteine inhibited the test organism, but would not form in the test system in amounts large enough to explain the observed inhibition. Roussin red salt was unstable in the test system and therefore was not the inhibitor. Roussin black salt, which was also inhibitory, could form in sufficient amounts to explain the inhibition. A complex of cysteine, iron, and nitric oxide was detected in the autoclaved solution of cysteine, ferrous sulfate, and sodium nitrite; this cysteine complex did not appear to be inhibitory, however, at levels which could form in the autoclaved medium. The observed inhibition may have been due to the combined effects of sublethal concentrations of each compound."} {"id": "PMID:173237", "title": "[Anomalies of corticotropin secretion in chromophobe adenomas].", "content": "Corticotrophic secretion has been studied in several groups of subjects during metopirone test and arginine L-Dopa infusion. In animals, a net plasma ACTH increase is observed under while it is inconstant after arginine L-Dopa. In hypopituitarism, metopirone ACTH levels are low and unchanged during the tests. In chromophobe adenoma, basal ACTH levels are high, ACTH increase is normal during test and significantly higher than in controls after L-Dopa injection. Significance of these metopirone corticotrophic abnormalities is discussed.", "contents": "[Anomalies of corticotropin secretion in chromophobe adenomas]. Corticotrophic secretion has been studied in several groups of subjects during metopirone test and arginine L-Dopa infusion. In animals, a net plasma ACTH increase is observed under while it is inconstant after arginine L-Dopa. In hypopituitarism, metopirone ACTH levels are low and unchanged during the tests. In chromophobe adenoma, basal ACTH levels are high, ACTH increase is normal during test and significantly higher than in controls after L-Dopa injection. Significance of these metopirone corticotrophic abnormalities is discussed."} {"id": "PMID:173240", "title": "Repair of heat-injured Clostridium perfringens spores during outgrowth.", "content": "Clostridium perfringens strain NCTC 8798 spores were injured by ultrahigh temperature treatment and were unable to outgrow in the presence of antibiotics used in selective enumeration media. Injured spores underwent repair in a nonselective laboratory medium and in foods.", "contents": "Repair of heat-injured Clostridium perfringens spores during outgrowth. Clostridium perfringens strain NCTC 8798 spores were injured by ultrahigh temperature treatment and were unable to outgrow in the presence of antibiotics used in selective enumeration media. Injured spores underwent repair in a nonselective laboratory medium and in foods."} {"id": "PMID:173236", "title": "Etiology of hyperuricemia.", "content": "Hyperuricemia is a common laboratory finding with significant clinical implications. It is easily detected, but its mechanisms may not be clearly elucidated. A scheme of pathogenesis has been outlined and diagrammed but much is conjectural; therefore, the classification is merely tentative. About 45 diseases or categories of conditions, 20 drugs, and nine states of intoxication have been surveyed. Hyperuricemia can be a multifactorial genetic disorder or a discrete response to a specific stimulus. It may be governed by a complex interplay of biochemical disorders for a lifetime duration, or it may be determined by environmental forces for a very transient course. Some conditions have both increased production of uric acid as well as decreased renal outflow. For many patients, the underlying mechanisms have not yet been elucidated.", "contents": "Etiology of hyperuricemia. Hyperuricemia is a common laboratory finding with significant clinical implications. It is easily detected, but its mechanisms may not be clearly elucidated. A scheme of pathogenesis has been outlined and diagrammed but much is conjectural; therefore, the classification is merely tentative. About 45 diseases or categories of conditions, 20 drugs, and nine states of intoxication have been surveyed. Hyperuricemia can be a multifactorial genetic disorder or a discrete response to a specific stimulus. It may be governed by a complex interplay of biochemical disorders for a lifetime duration, or it may be determined by environmental forces for a very transient course. Some conditions have both increased production of uric acid as well as decreased renal outflow. For many patients, the underlying mechanisms have not yet been elucidated."} {"id": "PMID:173243", "title": "Acquired ichthyosis. A sign of nonlymphoproliferative malignant disorders.", "content": "Acquired ichthyosis was recognized in four patients, in whom the associated malignant disorders were carcinoma of the lung, breast, and cervix. This skin lesion may be a valuable clinical sign in recognizing the existence of a malignant condition. Although the emergence of an ichthyosiform dermatosis may have serious prognostic implications, it may also be useful in monitoring the course of the malignant disorder and the patient's response to therapy. The relationship to nonlymphoproliferative malignant neoplasms may be more common than has been previously recognized.", "contents": "Acquired ichthyosis. A sign of nonlymphoproliferative malignant disorders. Acquired ichthyosis was recognized in four patients, in whom the associated malignant disorders were carcinoma of the lung, breast, and cervix. This skin lesion may be a valuable clinical sign in recognizing the existence of a malignant condition. Although the emergence of an ichthyosiform dermatosis may have serious prognostic implications, it may also be useful in monitoring the course of the malignant disorder and the patient's response to therapy. The relationship to nonlymphoproliferative malignant neoplasms may be more common than has been previously recognized."} {"id": "PMID:173244", "title": "Urinary 3'5' cyclic AMP. Diagnostic test in pseudohypoparathyroidism.", "content": "Measurement of urinary cyclic AMP (adenosine 3'5'-cyclic phosphate) and examination of calcium and phosphorus metabolism was carried out in two children with pseudohypoparathyroidism. In both patients infusion of parathyroid hormone failed to elicit any change in urinary cyclic AMP, while a dose-dependent increase in urinary cyclic AMP occurred in a normal control. The findings agree with concept of unresponsiveness of renal cortical tissue to parathyroid hormone in pseudohypoparathyroidism and provide further evidence that measurement of urinary cyclic AMP during parathyroid hormone infusion may be the method of choice in the diagnosis of this disease.", "contents": "Urinary 3'5' cyclic AMP. Diagnostic test in pseudohypoparathyroidism. Measurement of urinary cyclic AMP (adenosine 3'5'-cyclic phosphate) and examination of calcium and phosphorus metabolism was carried out in two children with pseudohypoparathyroidism. In both patients infusion of parathyroid hormone failed to elicit any change in urinary cyclic AMP, while a dose-dependent increase in urinary cyclic AMP occurred in a normal control. The findings agree with concept of unresponsiveness of renal cortical tissue to parathyroid hormone in pseudohypoparathyroidism and provide further evidence that measurement of urinary cyclic AMP during parathyroid hormone infusion may be the method of choice in the diagnosis of this disease."} {"id": "PMID:173246", "title": "Dense bodies and Langerhans granules after application of podophyllum resin.", "content": "The application of an alcoholic solution of podophyllum resin at concentrations above 10% for seven hours on guinea-pig udders increases the number of dense intracytoplasmic bodies in the Langerhans cells localized in the epidermis. A close relationship can be established between these inclusions and the typical Langerhans granules in view of the numerous intermediate forms with features of one or the other. Serial sections of these structures confirm the irregularity not only of the lysosome-like bodies but also of the Langerhans granules, which may be fusiform or oblong or even present two vesicular dilatations, one at each end of the rod.", "contents": "Dense bodies and Langerhans granules after application of podophyllum resin. The application of an alcoholic solution of podophyllum resin at concentrations above 10% for seven hours on guinea-pig udders increases the number of dense intracytoplasmic bodies in the Langerhans cells localized in the epidermis. A close relationship can be established between these inclusions and the typical Langerhans granules in view of the numerous intermediate forms with features of one or the other. Serial sections of these structures confirm the irregularity not only of the lysosome-like bodies but also of the Langerhans granules, which may be fusiform or oblong or even present two vesicular dilatations, one at each end of the rod."} {"id": "PMID:173247", "title": "[Tumor- and drug-induced cutaneous axonal dystrophy. An electronmicrocopy proof of multiple lamellated bodies].", "content": "A marked cutaneous axonal dystrophy has been observed electronmicroscopically for the first time in the skin of three patients: (a) lesion of pityriasis lichenoides chronica in a patient with bronchogenic carcinoma, (b) non involved skin of a patient with malignant melanoma and (c) non involved skin of a patient with gout and retinal damage after prolonged use of chloroquine. The affected myelinated and non myelinated axons showed distinct alterations of mitochondria and multiple osmiophilic lamellated bodies (LK). These changes were interpreted as a (poly-)neuropathy, due to the influence of toxic systemic agents, such as malignant tumor and abuse of drugs. Chloroquine is known to induce neural damage. Moreover, some other compounds (ergotamine, ethaverine, analgetic preparations) may also be responsible for the drug-induced axonal dystrophy described in this study.", "contents": "[Tumor- and drug-induced cutaneous axonal dystrophy. An electronmicrocopy proof of multiple lamellated bodies]. A marked cutaneous axonal dystrophy has been observed electronmicroscopically for the first time in the skin of three patients: (a) lesion of pityriasis lichenoides chronica in a patient with bronchogenic carcinoma, (b) non involved skin of a patient with malignant melanoma and (c) non involved skin of a patient with gout and retinal damage after prolonged use of chloroquine. The affected myelinated and non myelinated axons showed distinct alterations of mitochondria and multiple osmiophilic lamellated bodies (LK). These changes were interpreted as a (poly-)neuropathy, due to the influence of toxic systemic agents, such as malignant tumor and abuse of drugs. Chloroquine is known to induce neural damage. Moreover, some other compounds (ergotamine, ethaverine, analgetic preparations) may also be responsible for the drug-induced axonal dystrophy described in this study."} {"id": "PMID:173248", "title": "Sexual differentiation in Aspergillus nidulans: the requirement for manganese and the correlation between phosphoglucomutase and the synthesis of reserve material.", "content": "Aspergillus nidulans was completely devoid of fruit bodies when grown on manganese deficient cultures. This result was shown earlier to be due to a lack of alpha-1,3 glucan in the cell wall. Several enzymes of carbon and nitrogen metabolism were investigated in an attempt to explain the absence of this reserve material. Synthesis of glucose-6-phosphate dehydrogenase, phosphoglucoisomerase and aldolase, were not strongly affected by manganese deficiency. However, phosphoglucomutase showed only 60% of the activity of the control cultures and it was argued that this was connected with the low amounts of alpha-1,3 glucan synthesized. Malate dehydrogenase was the enzyme the least affected by manganese deficiency and the two to threefold higher activity measured after glucose depletion might indicate the induction of the glyoxylate cycle. An impaired glutamine synthetase could explain the increase in activity observed for NAD-glutamine dehydrogenase.", "contents": "Sexual differentiation in Aspergillus nidulans: the requirement for manganese and the correlation between phosphoglucomutase and the synthesis of reserve material. Aspergillus nidulans was completely devoid of fruit bodies when grown on manganese deficient cultures. This result was shown earlier to be due to a lack of alpha-1,3 glucan in the cell wall. Several enzymes of carbon and nitrogen metabolism were investigated in an attempt to explain the absence of this reserve material. Synthesis of glucose-6-phosphate dehydrogenase, phosphoglucoisomerase and aldolase, were not strongly affected by manganese deficiency. However, phosphoglucomutase showed only 60% of the activity of the control cultures and it was argued that this was connected with the low amounts of alpha-1,3 glucan synthesized. Malate dehydrogenase was the enzyme the least affected by manganese deficiency and the two to threefold higher activity measured after glucose depletion might indicate the induction of the glyoxylate cycle. An impaired glutamine synthetase could explain the increase in activity observed for NAD-glutamine dehydrogenase."} {"id": "PMID:173249", "title": "Comparative studies on sporulation-promotive actions on cyclic AMP, theophylline and caffeine in Saccharomyces cerevisiae.", "content": "Cyclic AMP, theophylline and caffeine promoted sporulation when added to a presporulation medium containing glucose. Caffeine promoted sporulation even when added to a presporulation medium containing acetate as the carbon source, but cyclic AMP and theophylline did not. Caffeine did not increase the intracellular cyclic AMP level, while theophylline did significantly when added to a presporulation medium containing glucose. Caffeine inhibited the vegatative DNA synthesis with little effect on RNA and protein synthesis, resulting in the increase in cell volume, dry weight, and RNA and protein contents, but cyclic AMP and theophylline did not show such effects.", "contents": "Comparative studies on sporulation-promotive actions on cyclic AMP, theophylline and caffeine in Saccharomyces cerevisiae. Cyclic AMP, theophylline and caffeine promoted sporulation when added to a presporulation medium containing glucose. Caffeine promoted sporulation even when added to a presporulation medium containing acetate as the carbon source, but cyclic AMP and theophylline did not. Caffeine did not increase the intracellular cyclic AMP level, while theophylline did significantly when added to a presporulation medium containing glucose. Caffeine inhibited the vegatative DNA synthesis with little effect on RNA and protein synthesis, resulting in the increase in cell volume, dry weight, and RNA and protein contents, but cyclic AMP and theophylline did not show such effects."} {"id": "PMID:173250", "title": "[Electron microscopy demonstration of fibrillar structures in the foot-and-mouth disease virus].", "content": "Purified FMD virus was heat treated and then examined by electron microscopy with the negative contrast technique. Fibrils of varying length and thickness were present; they were not present after ribonuclease treatment. They were similar to the fibrils described for other picornaviruses. Viral RNA was the essential component of these artificially arranged fibrils, which were composed of threads about 10 A wide, separated from one another by a gap of about 10 A.", "contents": "[Electron microscopy demonstration of fibrillar structures in the foot-and-mouth disease virus]. Purified FMD virus was heat treated and then examined by electron microscopy with the negative contrast technique. Fibrils of varying length and thickness were present; they were not present after ribonuclease treatment. They were similar to the fibrils described for other picornaviruses. Viral RNA was the essential component of these artificially arranged fibrils, which were composed of threads about 10 A wide, separated from one another by a gap of about 10 A."} {"id": "PMID:173251", "title": "Kinetics of neutralization of two strains of Myxovirus Parainfluenza 3 in the presence of complement and anti-gammaglobulin-serum.", "content": "Using the kinetics of neutralization, it was established that two strains of Myxovirus Parainfluenza 3 of cattle and sheep origin which are immunologicaly identical have a different sensitivity to early neutralizing antibodies of reconvalescent calf sera. Complement-dependent neutralizing antibodies, supplied by adding 5% guinea pig serum to the calf serum, appear earlier than the usual neutralizing antibodies. Goat anti-cattle gammaglobulin serum decreases the neutralizing activity of early reconvalescent serum and release some of the neutralizing virus from the virus-antibody complex. It is believed that the lability of the virus-antibody complex depends not only on the activity of the antibody, but also on some properties of the strains. The addition of complement stabilizes this complex. The previous addition of adenovirus antigen to bivalent cattle serum against Myxovirus Parainfluenza 3 and cattle adenovirus, decreases the complement-dependent neutralizing antibody of the serum against Myxovirus Parainfluenza 3. It is suggested that this is the possible mechanism for the mutual activation of mixed virus infections.", "contents": "Kinetics of neutralization of two strains of Myxovirus Parainfluenza 3 in the presence of complement and anti-gammaglobulin-serum. Using the kinetics of neutralization, it was established that two strains of Myxovirus Parainfluenza 3 of cattle and sheep origin which are immunologicaly identical have a different sensitivity to early neutralizing antibodies of reconvalescent calf sera. Complement-dependent neutralizing antibodies, supplied by adding 5% guinea pig serum to the calf serum, appear earlier than the usual neutralizing antibodies. Goat anti-cattle gammaglobulin serum decreases the neutralizing activity of early reconvalescent serum and release some of the neutralizing virus from the virus-antibody complex. It is believed that the lability of the virus-antibody complex depends not only on the activity of the antibody, but also on some properties of the strains. The addition of complement stabilizes this complex. The previous addition of adenovirus antigen to bivalent cattle serum against Myxovirus Parainfluenza 3 and cattle adenovirus, decreases the complement-dependent neutralizing antibody of the serum against Myxovirus Parainfluenza 3. It is suggested that this is the possible mechanism for the mutual activation of mixed virus infections."} {"id": "PMID:173252", "title": "[Haptoglobulin in domestic mammals. IV. Experimental influencing of the haptoglobulin level].", "content": "The effects of turpentine oil, vaccines, pyrogens, corticotrophin, prednisolone, adrenaline and autologous haemoglobin on the haptoglobin content of plasma was investigated in cattle and pigs. In comparison with rabbits, relatively small doses of turpentine oil led to a considerable increase in haptoglobin, a 50% increase occurring within 4 to 6 days in pigs and only 1.5-2 days in cattle. Bacterial products also increased haptoglobin. It was confirmed that pigs react very rapidly (after 8 hours) to injection of corticotrophin, prednisolone or adrenaline with an increase in plasma haptoglobin. Following complete saturation of infused haemoglobin by haptoglobin, new haptoglobin was rapidly formed, so that the initial haptoglobin concentration was regained about 24 hours after infusion of haemoglobin.", "contents": "[Haptoglobulin in domestic mammals. IV. Experimental influencing of the haptoglobulin level]. The effects of turpentine oil, vaccines, pyrogens, corticotrophin, prednisolone, adrenaline and autologous haemoglobin on the haptoglobin content of plasma was investigated in cattle and pigs. In comparison with rabbits, relatively small doses of turpentine oil led to a considerable increase in haptoglobin, a 50% increase occurring within 4 to 6 days in pigs and only 1.5-2 days in cattle. Bacterial products also increased haptoglobin. It was confirmed that pigs react very rapidly (after 8 hours) to injection of corticotrophin, prednisolone or adrenaline with an increase in plasma haptoglobin. Following complete saturation of infused haemoglobin by haptoglobin, new haptoglobin was rapidly formed, so that the initial haptoglobin concentration was regained about 24 hours after infusion of haemoglobin."} {"id": "PMID:173253", "title": "[Structure of the foot-and-mouth disease virus. 2. Various physical and chemical properties of the 12S components].", "content": "The 12S units were purified by heat treatment and acidification of purified, highly-concentrated virus, with separation of viral RNA by gel filtration. The following physical parameters were obtained: - partial specific volume 0.737 +/- 0.020 g/cm3; diffusion soefficient D020,W = 3.96 +/- 0.24 F; sedimentation coefficient S020,W = 12.1 +/- 0.5S; molecular weight 283,00 +/- 30,000 Dalton; refraction increment (determined by ultracentrifugation) was dn/dc = 0.189 +/- 0.010 cm3/g for white light of the \"HBO 200\". Examination of the 12S component by analytical ultracentrifugation and in sucrose and CsCl gradients showed that the product was uniform; density determined in CsCl was 1.302 +/- 0,00 s g/cm3. The ultraviolet absorption spectrum was characteristic of proteins; extinction values at 278 nm in a layer 1 cm thick and 10 mg/ml at pH was 13.9 +/- 1.9, while the ratio E278 nm/E250 = 2.2. Electron microscopy showed that the diameter was 11.0 +/- 1.6 nm. Morphology of 12S unit was discussed.", "contents": "[Structure of the foot-and-mouth disease virus. 2. Various physical and chemical properties of the 12S components]. The 12S units were purified by heat treatment and acidification of purified, highly-concentrated virus, with separation of viral RNA by gel filtration. The following physical parameters were obtained: - partial specific volume 0.737 +/- 0.020 g/cm3; diffusion soefficient D020,W = 3.96 +/- 0.24 F; sedimentation coefficient S020,W = 12.1 +/- 0.5S; molecular weight 283,00 +/- 30,000 Dalton; refraction increment (determined by ultracentrifugation) was dn/dc = 0.189 +/- 0.010 cm3/g for white light of the \"HBO 200\". Examination of the 12S component by analytical ultracentrifugation and in sucrose and CsCl gradients showed that the product was uniform; density determined in CsCl was 1.302 +/- 0,00 s g/cm3. The ultraviolet absorption spectrum was characteristic of proteins; extinction values at 278 nm in a layer 1 cm thick and 10 mg/ml at pH was 13.9 +/- 1.9, while the ratio E278 nm/E250 = 2.2. Electron microscopy showed that the diameter was 11.0 +/- 1.6 nm. Morphology of 12S unit was discussed."} {"id": "PMID:173254", "title": "REM phase deprivation and schizophrenia II.", "content": "Nine schizophrenic patients with active symptomatology were compared with seven patient controls in their response to two nights of rapid eye movement (REM) sleep deprivation. The control subjects demonstrate \"normal\" increases in total REM and percentage REM time increase on recovery nights compared to base line nights. The schizophrenic subjects differ substantially from the control subjects in both these measurements and show no perceptible change from base line nights on recovery nights. The effects of medication, anxiety, sleep loss, ceiling effects, and intensity change were not considered adequate to account for the above results. However, many questions, such as the specificity of this rebound failure to the schizophrenic patients and the possibility of a sleep disturbance factor operating independently of psychiatric diagnosis, remain to be answered.", "contents": "REM phase deprivation and schizophrenia II. Nine schizophrenic patients with active symptomatology were compared with seven patient controls in their response to two nights of rapid eye movement (REM) sleep deprivation. The control subjects demonstrate \"normal\" increases in total REM and percentage REM time increase on recovery nights compared to base line nights. The schizophrenic subjects differ substantially from the control subjects in both these measurements and show no perceptible change from base line nights on recovery nights. The effects of medication, anxiety, sleep loss, ceiling effects, and intensity change were not considered adequate to account for the above results. However, many questions, such as the specificity of this rebound failure to the schizophrenic patients and the possibility of a sleep disturbance factor operating independently of psychiatric diagnosis, remain to be answered."} {"id": "PMID:173255", "title": "[Morphogenesis of eleastotic transformation of breast cancer stroma (author's transl)].", "content": "Within the tissue proteins in stroma of breast cancer occured multifocal elastotic transformations. The transformations concern collagen bundles that are devoided of mucopolysaccharide substance. The fields of degenerated connective tissue take on the capacities to dye like elastic fibres. The authors suggest that the increase of elastotic material in stroma of breast cancer is bound with the collagen degradation that is caused by metabolites of cancer tissue. The phenomenon occured in all age groups and is not closely bound with the grade of histological malignancy of cancer.", "contents": "[Morphogenesis of eleastotic transformation of breast cancer stroma (author's transl)]. Within the tissue proteins in stroma of breast cancer occured multifocal elastotic transformations. The transformations concern collagen bundles that are devoided of mucopolysaccharide substance. The fields of degenerated connective tissue take on the capacities to dye like elastic fibres. The authors suggest that the increase of elastotic material in stroma of breast cancer is bound with the collagen degradation that is caused by metabolites of cancer tissue. The phenomenon occured in all age groups and is not closely bound with the grade of histological malignancy of cancer."} {"id": "PMID:173256", "title": "[Experimental investigations on the accumulation of radioactive compounds in autochtonal tumors in the rat (author's transl)].", "content": "For the first time results of investigations on rats with radioactive compounds in autochtonal tumors of the central nervous system, induced via placenta by Ethyl-Nitrose-Urea (ENU), are reported. In contrast to transplantation tumors the tumors induced by ENU are comparable in regard to the szintigrafic results with human brain tumors. The radiopharmaceuticals 131I-HSA, 99mTc-Pertechnetate, 203Hg-Chlormerodrin and 113m/111In-DTPA are similar to human brain tumors taken up by the ENU-tumors. For these findings it may be important, that the ENU-tumors are of neurogenic origin and do not differ histologically from the human brain tumors. The accumulation of the radioactive substances in ENU-tumors can be explained with the lesion at the blood-brain-barrier and at the blood-nerv-barrier. Therefore, it is discussed that the mechanism of the uptake is similar in human brain neoplasms and in ENU-tumors of the brain. The ENU-tumor model is suitable for testing new radiopharmaceuticals before their application in men.", "contents": "[Experimental investigations on the accumulation of radioactive compounds in autochtonal tumors in the rat (author's transl)]. For the first time results of investigations on rats with radioactive compounds in autochtonal tumors of the central nervous system, induced via placenta by Ethyl-Nitrose-Urea (ENU), are reported. In contrast to transplantation tumors the tumors induced by ENU are comparable in regard to the szintigrafic results with human brain tumors. The radiopharmaceuticals 131I-HSA, 99mTc-Pertechnetate, 203Hg-Chlormerodrin and 113m/111In-DTPA are similar to human brain tumors taken up by the ENU-tumors. For these findings it may be important, that the ENU-tumors are of neurogenic origin and do not differ histologically from the human brain tumors. The accumulation of the radioactive substances in ENU-tumors can be explained with the lesion at the blood-brain-barrier and at the blood-nerv-barrier. Therefore, it is discussed that the mechanism of the uptake is similar in human brain neoplasms and in ENU-tumors of the brain. The ENU-tumor model is suitable for testing new radiopharmaceuticals before their application in men."} {"id": "PMID:173257", "title": "[Results of a controlled clinical trial for evaluation of intensive preoperative irradiation in operable bronchial cancer (author's transl)].", "content": "To examine the value of an intensive preoperative irradiation on the bronchial carcinoma, 196 operable patients with tumors being histologically confirmed were divided into two groups by drawing the lot: 99 patients for preoperative irradiation, 97 for primary operation. The correspondence of the following criteria was tested and confirmed: age, sex, no symptons, histological tumor type. The preoperative irradiation dose amounted to 5,500 RHD (CO-60). Out of both groups the same number of patients was resected (83 and 85 respectively); within the preoperative irradiated group, however, 11 patients were omitted before the operation (information on reasons), while within the not irradiated group the number of thoracotomized but not resected cases was adequately greater (13). There is no statistically significant difference within the annual survival rate, although the mortality of the primarily operated patients is a bit more favourable. Quite the same is valid for postoperative mortality and complications. The local recurrences (in all cases of necropsy), however, are statistically significant reduced after preoperative irradiation. Since there is no influence on the rate of surviving, the conclusion is drawn that the majority of the operable cases has already developed small distant metastatic formations, being decisive for the prognosis before any therapy was performed. That is why a new prospective series with a low irradiation dose is started, where an increase of complications is not to be expected, but the possibility exists to influence local micrometastatic formations, that means an influence only to those cases with the probability of a low degree of remote metastatic formations.", "contents": "[Results of a controlled clinical trial for evaluation of intensive preoperative irradiation in operable bronchial cancer (author's transl)]. To examine the value of an intensive preoperative irradiation on the bronchial carcinoma, 196 operable patients with tumors being histologically confirmed were divided into two groups by drawing the lot: 99 patients for preoperative irradiation, 97 for primary operation. The correspondence of the following criteria was tested and confirmed: age, sex, no symptons, histological tumor type. The preoperative irradiation dose amounted to 5,500 RHD (CO-60). Out of both groups the same number of patients was resected (83 and 85 respectively); within the preoperative irradiated group, however, 11 patients were omitted before the operation (information on reasons), while within the not irradiated group the number of thoracotomized but not resected cases was adequately greater (13). There is no statistically significant difference within the annual survival rate, although the mortality of the primarily operated patients is a bit more favourable. Quite the same is valid for postoperative mortality and complications. The local recurrences (in all cases of necropsy), however, are statistically significant reduced after preoperative irradiation. Since there is no influence on the rate of surviving, the conclusion is drawn that the majority of the operable cases has already developed small distant metastatic formations, being decisive for the prognosis before any therapy was performed. That is why a new prospective series with a low irradiation dose is started, where an increase of complications is not to be expected, but the possibility exists to influence local micrometastatic formations, that means an influence only to those cases with the probability of a low degree of remote metastatic formations."} {"id": "PMID:173258", "title": "Subcellular distribution of phospholipids during liver damage induced by rare earths.", "content": "After intravenous injection of praseodymium nitrate, female Wistar rats develop fatty livers. In contrast to the marked increase of triglycerides, the phospholipid content was only increased by 50%. The subcellular distribution of phospholipids showed that major changes occur in the microsomal fraction within the first 24 hrs. Among the individual phospholipids only phosphatidylcholine and phosphatidylethanolamine concentrations were elevated. Further subfractioning revealed that phospholipid concentration increased in the smooth endoplasmic reticulum, whereas it decreased in the rough endoplasmic reticulum. The individual phospholipids in the smooth endoplasmic reticulum increased to the same degree as did the total phospholipids. On the other hand, in the rough endoplasmic reticulum only the lecithin fraction decreased, while all other phospholipids remained unchanged. Cytochrome P450, cytochrome b5, and glucose 6-phosphatase activity were drastically reduced in the rough endoplasmic reticulum, while no changes could be observed in the smooth endoplasmic reticulum. In the serum, phospholipid concentration fell to half the normal value within the first 24 hrs after praseodymium intoxication.", "contents": "Subcellular distribution of phospholipids during liver damage induced by rare earths. After intravenous injection of praseodymium nitrate, female Wistar rats develop fatty livers. In contrast to the marked increase of triglycerides, the phospholipid content was only increased by 50%. The subcellular distribution of phospholipids showed that major changes occur in the microsomal fraction within the first 24 hrs. Among the individual phospholipids only phosphatidylcholine and phosphatidylethanolamine concentrations were elevated. Further subfractioning revealed that phospholipid concentration increased in the smooth endoplasmic reticulum, whereas it decreased in the rough endoplasmic reticulum. The individual phospholipids in the smooth endoplasmic reticulum increased to the same degree as did the total phospholipids. On the other hand, in the rough endoplasmic reticulum only the lecithin fraction decreased, while all other phospholipids remained unchanged. Cytochrome P450, cytochrome b5, and glucose 6-phosphatase activity were drastically reduced in the rough endoplasmic reticulum, while no changes could be observed in the smooth endoplasmic reticulum. In the serum, phospholipid concentration fell to half the normal value within the first 24 hrs after praseodymium intoxication."} {"id": "PMID:173259", "title": "Demonstration of infectious DNA in transformed cells. II. Characterization of uptake of SV40-transformed mouse cell DNA by simian cells.", "content": "The initial steps in the DNA-transfer, or transfection, method of virus rescue were characterized using primary green monkey (GMK) cells exposed to SV40-transformed mouse (SV-3T3) cell DNA in the presence of 1 mg/ml DEAE-dextran. When large amounts (10-50mug) of high molecular weight DNA (greater than 10(7) daltons) were inoculated onto 10(6) GMK cells, usually less than 1 mug became cell-associated. DNA fragmented to a size of 1-3 X 10(6) daltons was bound more efficiently by the recipient cells, but generally only 5-10 per cent of the inoculum (representing 1-4 mug) was taken up. Approximately 50 per cent of the cell-associated DNA had penetrated to a DNase-resistant state by the end of the 30-minute incubation period. The effect of the size of thr transformed cell DNA molecule on the recovery of SV40 in transfection experiments was investigated. The trend appeared to be that rescue was more efficient with the larger molecular weight samples.", "contents": "Demonstration of infectious DNA in transformed cells. II. Characterization of uptake of SV40-transformed mouse cell DNA by simian cells. The initial steps in the DNA-transfer, or transfection, method of virus rescue were characterized using primary green monkey (GMK) cells exposed to SV40-transformed mouse (SV-3T3) cell DNA in the presence of 1 mg/ml DEAE-dextran. When large amounts (10-50mug) of high molecular weight DNA (greater than 10(7) daltons) were inoculated onto 10(6) GMK cells, usually less than 1 mug became cell-associated. DNA fragmented to a size of 1-3 X 10(6) daltons was bound more efficiently by the recipient cells, but generally only 5-10 per cent of the inoculum (representing 1-4 mug) was taken up. Approximately 50 per cent of the cell-associated DNA had penetrated to a DNase-resistant state by the end of the 30-minute incubation period. The effect of the size of thr transformed cell DNA molecule on the recovery of SV40 in transfection experiments was investigated. The trend appeared to be that rescue was more efficient with the larger molecular weight samples."} {"id": "PMID:173260", "title": "Specific cleavage of Sendai virus nucleocapsid protein subunits during virus storage.", "content": "The alteration of whole Sendai virus and especially of its nucleocapsid polypeptides, during storage of the virus at 4 degree C in the allantoic fluids in which it was cultivated, has cultivated, has been studied by sodium dodecyl sulfate gel electrophoresis. During virus storage the nucleocapsid protein subunits with a molecular weight of 60,000 and the putative inner envelope protein with a molecular weight of 38,000 were mainly affected. Both virus components were partially degraded to smaller components. Examination of nucleocapsids isolated from \"stored\" virus showed that, in addition to the 60,000-molecular weight polypetide component, a smaller polypeptide component with a molecular weight of 46,000 appeared. The relative proportion of the small component increased with the storage period: a kind of specific conversion of large to small components occurred during storage. Since viruses kept in the absence of allantoic fluids revealed no similar modifications of their polypeptides, we concluded that a cellular component present in the allantoic fluids - very likely of enzymatic nature - is responsible for the observed cleavage of virus polypeptides.", "contents": "Specific cleavage of Sendai virus nucleocapsid protein subunits during virus storage. The alteration of whole Sendai virus and especially of its nucleocapsid polypeptides, during storage of the virus at 4 degree C in the allantoic fluids in which it was cultivated, has cultivated, has been studied by sodium dodecyl sulfate gel electrophoresis. During virus storage the nucleocapsid protein subunits with a molecular weight of 60,000 and the putative inner envelope protein with a molecular weight of 38,000 were mainly affected. Both virus components were partially degraded to smaller components. Examination of nucleocapsids isolated from \"stored\" virus showed that, in addition to the 60,000-molecular weight polypetide component, a smaller polypeptide component with a molecular weight of 46,000 appeared. The relative proportion of the small component increased with the storage period: a kind of specific conversion of large to small components occurred during storage. Since viruses kept in the absence of allantoic fluids revealed no similar modifications of their polypeptides, we concluded that a cellular component present in the allantoic fluids - very likely of enzymatic nature - is responsible for the observed cleavage of virus polypeptides."} {"id": "PMID:173261", "title": "Effect of tetraethyl thiuram disulfide (disulfiram) on the multiplication of enveloped viruses.", "content": "Disulfiram at concentrations between 0.1 and 0.3 mM inhibits the multiplication of Semliki Forest virus (SFV), fowl plague virus (FPV), Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and pseudorabies virus (PRV), when administered 1 hour before and during adsorption. There is, however, no inhibition of virus multiplication, when the drug is added after adsorption onto chick embryo cells. Disulfiram interferes neither with the receptors of the virus nor of erythrocytes, and it does not prevent virus adsorption. Possibly an early step in virus multiplication is affected by disculfiram. Infected cells once treated with the drug recover after some time of incubation in an ingibitor-free medium. The inhibitory state can be maintained, however, if relatively low doses of disulfiram are present in the culture medium also after adsorption. Disulfiram has no effect on macromolecular synthesis of the host cells. It has, however, a marked affect on membrane function. While virus multiplication is readily inhibited by disulfiram when chick embryo or BHK cells were investigated, virus multiplication in HeLa cells is almost resestant against the action of disulfiram.", "contents": "Effect of tetraethyl thiuram disulfide (disulfiram) on the multiplication of enveloped viruses. Disulfiram at concentrations between 0.1 and 0.3 mM inhibits the multiplication of Semliki Forest virus (SFV), fowl plague virus (FPV), Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and pseudorabies virus (PRV), when administered 1 hour before and during adsorption. There is, however, no inhibition of virus multiplication, when the drug is added after adsorption onto chick embryo cells. Disulfiram interferes neither with the receptors of the virus nor of erythrocytes, and it does not prevent virus adsorption. Possibly an early step in virus multiplication is affected by disculfiram. Infected cells once treated with the drug recover after some time of incubation in an ingibitor-free medium. The inhibitory state can be maintained, however, if relatively low doses of disulfiram are present in the culture medium also after adsorption. Disulfiram has no effect on macromolecular synthesis of the host cells. It has, however, a marked affect on membrane function. While virus multiplication is readily inhibited by disulfiram when chick embryo or BHK cells were investigated, virus multiplication in HeLa cells is almost resestant against the action of disulfiram."} {"id": "PMID:173262", "title": "SV40 induced polypeptides in infected and transformed cells.", "content": "5 structural (VP) and 3 non-structural (NSVP) SV40 induced polypeptides which display two kinetic patterns of synthesis are identified in infected cells. NSVP 1 and 2 are \"early\" functions of which only NSVP 1 is present in transformed cells; NSVP 3 is \"late\" function which is also present in a line (T-22) of transformed AGMK.", "contents": "SV40 induced polypeptides in infected and transformed cells. 5 structural (VP) and 3 non-structural (NSVP) SV40 induced polypeptides which display two kinetic patterns of synthesis are identified in infected cells. NSVP 1 and 2 are \"early\" functions of which only NSVP 1 is present in transformed cells; NSVP 3 is \"late\" function which is also present in a line (T-22) of transformed AGMK."} {"id": "PMID:173263", "title": "Inhibition of Newcastle disease virus-induced fever in rabbits by cycloheximide.", "content": "Pretreatment with cycloheximide prevents virus-induced fever in rabbits. Compared to the febrile control animals, CH-pretreated afebrile animals exhibit similar concentrations of endogenous pyrogen in the blood and of prostaglandins of the E-group and adenosine 3', 5'-cycle monophosphate in the cerebrospinal fluid. The fever response seems to involve one or several additional so far unknown mediators which are sensitive to cycloheximide.", "contents": "Inhibition of Newcastle disease virus-induced fever in rabbits by cycloheximide. Pretreatment with cycloheximide prevents virus-induced fever in rabbits. Compared to the febrile control animals, CH-pretreated afebrile animals exhibit similar concentrations of endogenous pyrogen in the blood and of prostaglandins of the E-group and adenosine 3', 5'-cycle monophosphate in the cerebrospinal fluid. The fever response seems to involve one or several additional so far unknown mediators which are sensitive to cycloheximide."} {"id": "PMID:173266", "title": "[Influence of hormones on the functional activity of the regenerating cortex of the enucleated adrenal in situ].", "content": "The functional activity of the regenerating cortex was studied in 90 female albino rats (150-200 g) after ablation of the right adrenal and enucleation of the left one. In the period of active growth of the regenerating tissue (10 days after operation) the functional activity of parenchymatous cells was low which is evidenced by poor content of both lipids and \"ketosteroids\". In parallel with reparation of the adrenal adrenocortical tissue mass the content of physiologically active substances was also restored (20 days after operation). After injection of hydrocortizone (daily dosage 2,5 mg) the growth and differentiation of the bundle-reticular zone in the regenerating area was inhibited. In the glomerular zone the reactions to lipids and \"ketosteroids\" were mainly similar to those in the glomerular zone of intact adrenal. After injection of ACTH (daily dosage 5 or 10 mg) during 10 days the regenerating area was functionally better developed than in the control since moderately pronounced reactions to \"ketosteroids\" and lipids appeared in it. Fairly high content of these substances in the regenerated cortex after 20 days of injections of ACTH (10 units) as well as presence of secondary necrobiotic changes pointed to functional overstrain of the newly formed organ.", "contents": "[Influence of hormones on the functional activity of the regenerating cortex of the enucleated adrenal in situ]. The functional activity of the regenerating cortex was studied in 90 female albino rats (150-200 g) after ablation of the right adrenal and enucleation of the left one. In the period of active growth of the regenerating tissue (10 days after operation) the functional activity of parenchymatous cells was low which is evidenced by poor content of both lipids and \"ketosteroids\". In parallel with reparation of the adrenal adrenocortical tissue mass the content of physiologically active substances was also restored (20 days after operation). After injection of hydrocortizone (daily dosage 2,5 mg) the growth and differentiation of the bundle-reticular zone in the regenerating area was inhibited. In the glomerular zone the reactions to lipids and \"ketosteroids\" were mainly similar to those in the glomerular zone of intact adrenal. After injection of ACTH (daily dosage 5 or 10 mg) during 10 days the regenerating area was functionally better developed than in the control since moderately pronounced reactions to \"ketosteroids\" and lipids appeared in it. Fairly high content of these substances in the regenerated cortex after 20 days of injections of ACTH (10 units) as well as presence of secondary necrobiotic changes pointed to functional overstrain of the newly formed organ."} {"id": "PMID:173267", "title": "[Histochemistry of the oxidation-reduction enzymes in the cells of neuroectodermal tumors].", "content": "The activity of 8 enzymes (dehydrogenase and diaphorase) in cells of 110 neuroectodermal tumours was studied. The overall assessment showed that the activity of these enzymes varied: the highest was noted for NAD-diaphorase and lactadehydrogenase, the lowest--for enzymes of Krebs' cycle. The activity of dehydrogenase and diaphorase was different in neuroectodermal tumours of different origin. Not infrequently, there was observed \"enzymatic polymorphism\" of the cells of one and the same tumour. A higher activity of these enzymes in tumour cells, as a rule, correlated with a greater amount of cytoplasma and with a shift to the latter of the nucleo-cytoplasmatic ratio. Metabolism of tumour and reactively hypertrophied astrocytes, as judged by some histochemical findings, showed traits of similarity.", "contents": "[Histochemistry of the oxidation-reduction enzymes in the cells of neuroectodermal tumors]. The activity of 8 enzymes (dehydrogenase and diaphorase) in cells of 110 neuroectodermal tumours was studied. The overall assessment showed that the activity of these enzymes varied: the highest was noted for NAD-diaphorase and lactadehydrogenase, the lowest--for enzymes of Krebs' cycle. The activity of dehydrogenase and diaphorase was different in neuroectodermal tumours of different origin. Not infrequently, there was observed \"enzymatic polymorphism\" of the cells of one and the same tumour. A higher activity of these enzymes in tumour cells, as a rule, correlated with a greater amount of cytoplasma and with a shift to the latter of the nucleo-cytoplasmatic ratio. Metabolism of tumour and reactively hypertrophied astrocytes, as judged by some histochemical findings, showed traits of similarity."} {"id": "PMID:173268", "title": "Neostigmine methylsulfate. Does it have a chronic effect as well as a transient one?", "content": "Three groups of 200-gm rats were injected subcutaneously with neostigmine methylsulfate (1 mg/kg/day) for 7, 30, and 100 days. Electrophysiological changes were assessed in vitro, using microelectrode techniques to examine diaphragm muscles of treated and untreated animals. Miniature end-plate potential (MEPP) amplitude decreased in neostigmine-treated preparations. Guanidine hydrochloride enhances transmitter release and increases MEPP frequency in control preparations. Neostigmine-treated animals examined between 6 to 72 hours after discontinuation of neostigmine therapy showed impaired response to the facilitating influence of guanidine. Recovery of response to guanidine was inversely related to length of treatment with neostigmine. Results of electron-microscopic examination of motor end-plates in treated animals revealed ultrastructural changes, including simplified end-plates, and, occasionally, multiple, separate, junctional regions. Therefore, the chronic administration of cholinesterase inhibitors in man may have a deleterious effect, as well as a transient beneficial one.", "contents": "Neostigmine methylsulfate. Does it have a chronic effect as well as a transient one? Three groups of 200-gm rats were injected subcutaneously with neostigmine methylsulfate (1 mg/kg/day) for 7, 30, and 100 days. Electrophysiological changes were assessed in vitro, using microelectrode techniques to examine diaphragm muscles of treated and untreated animals. Miniature end-plate potential (MEPP) amplitude decreased in neostigmine-treated preparations. Guanidine hydrochloride enhances transmitter release and increases MEPP frequency in control preparations. Neostigmine-treated animals examined between 6 to 72 hours after discontinuation of neostigmine therapy showed impaired response to the facilitating influence of guanidine. Recovery of response to guanidine was inversely related to length of treatment with neostigmine. Results of electron-microscopic examination of motor end-plates in treated animals revealed ultrastructural changes, including simplified end-plates, and, occasionally, multiple, separate, junctional regions. Therefore, the chronic administration of cholinesterase inhibitors in man may have a deleterious effect, as well as a transient beneficial one."} {"id": "PMID:173269", "title": "Myasthenic syndrome studied with single fiber electromyography.", "content": "A patient with the myasthenic syndrome was investigated with single fiber electromyography (SFEMG). It was found that 35 of 36 potential pairs had increased \"jitter\" and that 29 of these demonstrated impulse blockings. There was improvement in neuromuscular transmission with higher rates of innervation. Transmission worsened following rest. The SFEMG findings at the motor end-plate level correlate well with the results of repetitive stimulation and in vitro studies.", "contents": "Myasthenic syndrome studied with single fiber electromyography. A patient with the myasthenic syndrome was investigated with single fiber electromyography (SFEMG). It was found that 35 of 36 potential pairs had increased \"jitter\" and that 29 of these demonstrated impulse blockings. There was improvement in neuromuscular transmission with higher rates of innervation. Transmission worsened following rest. The SFEMG findings at the motor end-plate level correlate well with the results of repetitive stimulation and in vitro studies."} {"id": "PMID:173270", "title": "Idoxuridine ocular insert therapy. Use in treatment of experimental Herpes simplex keratitis.", "content": "Therapy of acute Herpes simplex keratitis in rabbits with idoxuridine-releasing ocular inserts showed that an application rate of 30mug/hr gave significantly better results than conventional treatment with idoxuridine drops and ointment while exposing the eye to 40% less drug. Delivery rates lower than this were equal or not as effective as drop and ointment therapy and rates up to 100 mug/hr did not produce significantly better results than rates of 30mug/hr. Serial viral cultures demonstrated the persistence of virus beyond the period of clinical resolution of disease in all treatment groups, indicating that therapy should be continued longer than apparent resolution of disease.", "contents": "Idoxuridine ocular insert therapy. Use in treatment of experimental Herpes simplex keratitis. Therapy of acute Herpes simplex keratitis in rabbits with idoxuridine-releasing ocular inserts showed that an application rate of 30mug/hr gave significantly better results than conventional treatment with idoxuridine drops and ointment while exposing the eye to 40% less drug. Delivery rates lower than this were equal or not as effective as drop and ointment therapy and rates up to 100 mug/hr did not produce significantly better results than rates of 30mug/hr. Serial viral cultures demonstrated the persistence of virus beyond the period of clinical resolution of disease in all treatment groups, indicating that therapy should be continued longer than apparent resolution of disease."} {"id": "PMID:173271", "title": "Bilateral synchronous mixed tumors of the parotid gland.", "content": "A 62-year-old man had bilateral parotid masses. This case represents a rare occurrence of bilateral synchronous mixed tumors of the parotid gland. We discuss this case, including preoperative evaluation, reason for rarity, treatment, and a review of the literature.", "contents": "Bilateral synchronous mixed tumors of the parotid gland. A 62-year-old man had bilateral parotid masses. This case represents a rare occurrence of bilateral synchronous mixed tumors of the parotid gland. We discuss this case, including preoperative evaluation, reason for rarity, treatment, and a review of the literature."} {"id": "PMID:173272", "title": "Recurrent benign mixed tumor and the facial nerve.", "content": "In surgical treatment of patients with recurrent benign mixed tumor, the surgeon strives to preserve the facial nerve. If there is inadvertent nerve injury, immediate repair is the treatment of choice. We report two patients with recurrent benign mixed tumor in whom the facial nerve was deliberately sacrificed. Repair of the nerve was accomplished by nerve grafts. Gross and microscopic tissue examination are presented in each instance, supporting the concept of en bloc removal of tumor and nerve. Such a surgical procedure is reserved only for a highly selected group of patients.", "contents": "Recurrent benign mixed tumor and the facial nerve. In surgical treatment of patients with recurrent benign mixed tumor, the surgeon strives to preserve the facial nerve. If there is inadvertent nerve injury, immediate repair is the treatment of choice. We report two patients with recurrent benign mixed tumor in whom the facial nerve was deliberately sacrificed. Repair of the nerve was accomplished by nerve grafts. Gross and microscopic tissue examination are presented in each instance, supporting the concept of en bloc removal of tumor and nerve. Such a surgical procedure is reserved only for a highly selected group of patients."} {"id": "PMID:173273", "title": "Encephalomyocarditis virus infection of pigs. 1. An outbreak in New South Wales.", "content": "Substantial pig mortalities due to heart disease caused by EMC virus infection are described. The majority occurred in 1970 in conjunction with a rodent plague, but retrospective diagnosis of occasional similar mortalities in previous years was possible. Mortality rates in pigs aged 3 to 16 weeks ranged from a few percent to over 50% and the rate was generally highest in younger animals. It is likely that a considerable proportion of cases was sub-clinical. Focal or diffuse pale areas occurred in the myocardium, the wall of the conus arteriosus being most severely affected. In a few animals, resolving lesions were present. Encephalomyocarditis virus was consistently recovered from pigs with acute heart lesions, but not from those in which myocardial fibrosis had commenced. The virus was demonstrated in rodents, although the dependence of pig disease on rodent-derived virus could not be established. Because of similarities between EMC and FMD myocarditides in pigs, specific diagnosis by virus isolation and identification should be obtained whenever possible.", "contents": "Encephalomyocarditis virus infection of pigs. 1. An outbreak in New South Wales. Substantial pig mortalities due to heart disease caused by EMC virus infection are described. The majority occurred in 1970 in conjunction with a rodent plague, but retrospective diagnosis of occasional similar mortalities in previous years was possible. Mortality rates in pigs aged 3 to 16 weeks ranged from a few percent to over 50% and the rate was generally highest in younger animals. It is likely that a considerable proportion of cases was sub-clinical. Focal or diffuse pale areas occurred in the myocardium, the wall of the conus arteriosus being most severely affected. In a few animals, resolving lesions were present. Encephalomyocarditis virus was consistently recovered from pigs with acute heart lesions, but not from those in which myocardial fibrosis had commenced. The virus was demonstrated in rodents, although the dependence of pig disease on rodent-derived virus could not be established. Because of similarities between EMC and FMD myocarditides in pigs, specific diagnosis by virus isolation and identification should be obtained whenever possible."} {"id": "PMID:173274", "title": "Encephalomyocarditis virus infection of pigs. 2. Experimental disease.", "content": "Encephalomycarditis virus recovered from a pig mortality in New South Wales was used to produce experimental infections. Of 34 pigs exposed, 17 died and a further 7 were found to have severe heart lesions when killed. Deaths occurred from 2 to 11 days after exposure with a mode of approximately 3 days. Ten of 11 pigs exposed by intramuscular injection died and the remaining pig was killed after 28 days and found to have severe resolving heart lesions. Of 15 pigs exposed per os to various doses of virus, 6 died, 4 were killed and found to have severe heart lesions and 5 were apparently not infected. Intranasal exposure of 8 pigs resulted in 1 death and 4 pigs with mild to severe heart lesions. Different doses of virus and routes of exposure did not substantially influence the character of the lesions. Lesions were similar to those found previously in field cases, and virus was recovered from all of 19 animals examined with severe acute lesions of 10 days standing or less.", "contents": "Encephalomyocarditis virus infection of pigs. 2. Experimental disease. Encephalomycarditis virus recovered from a pig mortality in New South Wales was used to produce experimental infections. Of 34 pigs exposed, 17 died and a further 7 were found to have severe heart lesions when killed. Deaths occurred from 2 to 11 days after exposure with a mode of approximately 3 days. Ten of 11 pigs exposed by intramuscular injection died and the remaining pig was killed after 28 days and found to have severe resolving heart lesions. Of 15 pigs exposed per os to various doses of virus, 6 died, 4 were killed and found to have severe heart lesions and 5 were apparently not infected. Intranasal exposure of 8 pigs resulted in 1 death and 4 pigs with mild to severe heart lesions. Different doses of virus and routes of exposure did not substantially influence the character of the lesions. Lesions were similar to those found previously in field cases, and virus was recovered from all of 19 animals examined with severe acute lesions of 10 days standing or less."} {"id": "PMID:173275", "title": "Investigation of equine infectious anaemia in Queensland using gel diffusion.", "content": "An antigen for the gel diffusion test for equine infectious anaemia (EIA) was prepared from the spleen of a horse experimentally infected with the CQ strain of the virus. The antigen produced a single, distinct line of precipitation when tested against a range of known positive serums, and did not react with pre-inoculation and known negative serums. Extracts prepared from uninfected spleens displayed no reaction when similarly tested. Serum from 34 of 451 Queensland horses contained detectable levels of antibody to EIA virus. The positive serums were from horses in widely separated areas of the State.", "contents": "Investigation of equine infectious anaemia in Queensland using gel diffusion. An antigen for the gel diffusion test for equine infectious anaemia (EIA) was prepared from the spleen of a horse experimentally infected with the CQ strain of the virus. The antigen produced a single, distinct line of precipitation when tested against a range of known positive serums, and did not react with pre-inoculation and known negative serums. Extracts prepared from uninfected spleens displayed no reaction when similarly tested. Serum from 34 of 451 Queensland horses contained detectable levels of antibody to EIA virus. The positive serums were from horses in widely separated areas of the State."} {"id": "PMID:173276", "title": "Infectious tenosynovitis (viral arthritis): characterization of a Connecticut viral isolant as a reovirus and evidence of viral egg transmission by reovirus-infected broiler breeders.", "content": "Connecticut isolant S1133 of tenosynovitis was characterized as a reovirus by physicochemical, biological, and morphologic studies. After inoculation of 35-week-old broiler breeders with tenosynovitis virus by subcutaneous route, virus was found in embryos of eggs laid by the breeders during a period of 8 to 12 days after inoculation.", "contents": "Infectious tenosynovitis (viral arthritis): characterization of a Connecticut viral isolant as a reovirus and evidence of viral egg transmission by reovirus-infected broiler breeders. Connecticut isolant S1133 of tenosynovitis was characterized as a reovirus by physicochemical, biological, and morphologic studies. After inoculation of 35-week-old broiler breeders with tenosynovitis virus by subcutaneous route, virus was found in embryos of eggs laid by the breeders during a period of 8 to 12 days after inoculation."} {"id": "PMID:173280", "title": "Variation between electrophoretically identical alleles at the alcohol dehydrogenase locus in Drosophila melanogaster.", "content": "A new variant of alcohol dehydrogenase (ADH 7lk) was found in a laboratory stock of Drosophila melanogaster. ADH in this stock had the same electrophoretic mobility as the F variant both on acrylamide and on agar. Activity levels were similar to the levels in F flies at temperature between 15 and 25 C. But while ADH F enzyme is inactivated rapidly at 40 C, ADH 7lk is still active. Also, ADH S is not inactivated at this temperature, but has a far lower activity per fly than ADH 7lk. Genetic analysis showed that the new variant is an allele of the Adh locus.", "contents": "Variation between electrophoretically identical alleles at the alcohol dehydrogenase locus in Drosophila melanogaster. A new variant of alcohol dehydrogenase (ADH 7lk) was found in a laboratory stock of Drosophila melanogaster. ADH in this stock had the same electrophoretic mobility as the F variant both on acrylamide and on agar. Activity levels were similar to the levels in F flies at temperature between 15 and 25 C. But while ADH F enzyme is inactivated rapidly at 40 C, ADH 7lk is still active. Also, ADH S is not inactivated at this temperature, but has a far lower activity per fly than ADH 7lk. Genetic analysis showed that the new variant is an allele of the Adh locus."} {"id": "PMID:173278", "title": "The roles of the infectious bursal agent and several avian adenoviruses in the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis.", "content": "The effect that breeder-flock immune status regarding the infectious bursal agent (IBA) and two avian adenoviruses (DPI-1 and DPI-2) has on the susceptibility of their commercially reared Delmarva broiler progeny to the hemorrhagic-aplastic-anemia syndrome and concurrent gangrenous dermatitis was determined. Lack of immunity to the IBA in breeder flocks was related to an increased susceptibility of progeny to anemia and dermatitis. Breeder-flock immunity to the two adenoviruses tested could not be related to the resistance or susceptibility of their progeny to the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis.", "contents": "The roles of the infectious bursal agent and several avian adenoviruses in the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis. The effect that breeder-flock immune status regarding the infectious bursal agent (IBA) and two avian adenoviruses (DPI-1 and DPI-2) has on the susceptibility of their commercially reared Delmarva broiler progeny to the hemorrhagic-aplastic-anemia syndrome and concurrent gangrenous dermatitis was determined. Lack of immunity to the IBA in breeder flocks was related to an increased susceptibility of progeny to anemia and dermatitis. Breeder-flock immunity to the two adenoviruses tested could not be related to the resistance or susceptibility of their progeny to the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis."} {"id": "PMID:173281", "title": "Effects of increased mechanical work by isolated perfused rat heart during production or uptake of ketone bodies. Assessment of mitochondrial oxidized to reduced free nicotinamide-adenine dinucleotide ratios and oxaloacetate concentrations.", "content": "Metabolic effects of increased mechanical work were studied by comparing isolated pumping rat hearts perfused by the atrial-filling technique with aortic-perfused non-pumping hearts perfused by the technique of Langendorff. The initial medium usually contained glucose (11 mm) and palmitate (0.6 mm bound to 0.1 mm albumin). During increased heart work (comparing pumping with non-pumping hearts) the uptake of oxygen and glucose increased threefold, but that of free fatty acids was unchanged. Tissue contents of alpha-oxoglutarate, NH4+, malate, lactate, pyruvate and Pi rose with increased heart work, but contents of ATP, phosphocreatine and citrate fell. Ketone bodies were produced with a ratio of beta-hydroxybutyrate/acetoacetate of about 3:1 in both pumping and non-pumping hearts but with higher net production rates in non-pumping hearts. When ketone bodies were added in relatively high concentrations (total 4 mm) to a glucose (11 mm) medium the medium, ratios of beta-hydroxybutyrate/acetoacetate were not steady even after 60 min of perfusion. The validity of calculating mitochondrial free NAD+/NADH ratios from the tissue contents of the reactants of the glutamate dehydrogenase system or the beta-hydroxybutyrate dehydrogenase system is assessed. The activities of these enzymes are considerably less in the rat heart than in the rat liver, introducing reservations into the application to the heart of the principles used by Williamson et al. (1967) for calculation of mitochondrial free NAD+/NADH ratios of liver mitochondria...", "contents": "Effects of increased mechanical work by isolated perfused rat heart during production or uptake of ketone bodies. Assessment of mitochondrial oxidized to reduced free nicotinamide-adenine dinucleotide ratios and oxaloacetate concentrations. Metabolic effects of increased mechanical work were studied by comparing isolated pumping rat hearts perfused by the atrial-filling technique with aortic-perfused non-pumping hearts perfused by the technique of Langendorff. The initial medium usually contained glucose (11 mm) and palmitate (0.6 mm bound to 0.1 mm albumin). During increased heart work (comparing pumping with non-pumping hearts) the uptake of oxygen and glucose increased threefold, but that of free fatty acids was unchanged. Tissue contents of alpha-oxoglutarate, NH4+, malate, lactate, pyruvate and Pi rose with increased heart work, but contents of ATP, phosphocreatine and citrate fell. Ketone bodies were produced with a ratio of beta-hydroxybutyrate/acetoacetate of about 3:1 in both pumping and non-pumping hearts but with higher net production rates in non-pumping hearts. When ketone bodies were added in relatively high concentrations (total 4 mm) to a glucose (11 mm) medium the medium, ratios of beta-hydroxybutyrate/acetoacetate were not steady even after 60 min of perfusion. The validity of calculating mitochondrial free NAD+/NADH ratios from the tissue contents of the reactants of the glutamate dehydrogenase system or the beta-hydroxybutyrate dehydrogenase system is assessed. The activities of these enzymes are considerably less in the rat heart than in the rat liver, introducing reservations into the application to the heart of the principles used by Williamson et al. (1967) for calculation of mitochondrial free NAD+/NADH ratios of liver mitochondria..."} {"id": "PMID:173282", "title": "Relationship between elongation factor I- and elongation factor II- dependent guanosine triphosphatase activities of ribosomes. Inhibition of both activities by ricin.", "content": "The elongation factor 1- and elongation factor 2-dependent GTPase (guanosine triphosphatase) activities of ribosomes are inhibited by ricin, a toxic protein known to inactivate the 60S ribosomal subunit. It is suggested that also in eukaryotic ribosomes a \"GTPase site', located on the larger subunit, is common to the two elongation factors.", "contents": "Relationship between elongation factor I- and elongation factor II- dependent guanosine triphosphatase activities of ribosomes. Inhibition of both activities by ricin. The elongation factor 1- and elongation factor 2-dependent GTPase (guanosine triphosphatase) activities of ribosomes are inhibited by ricin, a toxic protein known to inactivate the 60S ribosomal subunit. It is suggested that also in eukaryotic ribosomes a \"GTPase site', located on the larger subunit, is common to the two elongation factors."} {"id": "PMID:173279", "title": "Hemagglutinating properties of CELO, an oncogenic avian adenovirus.", "content": "Chicken-embryo-lethal-orphan (CELO) virus, Phelps strain, agglutinated erythrocytes at 37 C. The hemagglutinating activity, which is a function of complete and incomplete virus particles, was sensitive to heat but not to pH. The soluble components of the virus were similar in sedimentation characteristics to those obtained from human adenovirus type 1. The effects of chemical and physical agents on CELO hemagglutinin, CELO infectivity, and red-cell receptors suggested that the last were protein in nature and that cell-virus attachment was mediated by amino groups on the virion. The attachment of virus to red blood cells via the penton projection was demonstrated by electron microscopy.", "contents": "Hemagglutinating properties of CELO, an oncogenic avian adenovirus. Chicken-embryo-lethal-orphan (CELO) virus, Phelps strain, agglutinated erythrocytes at 37 C. The hemagglutinating activity, which is a function of complete and incomplete virus particles, was sensitive to heat but not to pH. The soluble components of the virus were similar in sedimentation characteristics to those obtained from human adenovirus type 1. The effects of chemical and physical agents on CELO hemagglutinin, CELO infectivity, and red-cell receptors suggested that the last were protein in nature and that cell-virus attachment was mediated by amino groups on the virion. The attachment of virus to red blood cells via the penton projection was demonstrated by electron microscopy."} {"id": "PMID:173277", "title": "Adenovirus respiratory infection in turkey poults.", "content": "A virus from turkey poults with respiratory signs was isolated in specific-pathogen-free embryonated chicken eggs and subsequently adapted to chicken embryo fibroblast and turkey kidney cell cultures, where round cell formation was observed. The cloned virus was ether-resistant and incorporated tridiated thymidine. Intra-nuclear icosahedral virus particles of 80 nm were detected. These physicochemical characteristics place this isolant into the adenovirus group of viruses. The disease was experimentally reproduced by intratracheal inoculation of one-day-old turkey poults. Snicking occurred in 100% of the birds and mortality reached 50%. CELO (Phelps strain) antiserum neutralized uncloned and cloned CUA-2 in chicken embryos and uncloned virus in chicken embryo fibroblast cell cultures. Quail bronchitis virus antiserum neutralized cloned CUA-2 in TK cells. Agar-gel precipitin lines of identity were formed using CELO antiserum and postinoculation sera from experimentally infected turkeys. Serologically, this virus should be classified as a type-1 adenovirus.", "contents": "Adenovirus respiratory infection in turkey poults. A virus from turkey poults with respiratory signs was isolated in specific-pathogen-free embryonated chicken eggs and subsequently adapted to chicken embryo fibroblast and turkey kidney cell cultures, where round cell formation was observed. The cloned virus was ether-resistant and incorporated tridiated thymidine. Intra-nuclear icosahedral virus particles of 80 nm were detected. These physicochemical characteristics place this isolant into the adenovirus group of viruses. The disease was experimentally reproduced by intratracheal inoculation of one-day-old turkey poults. Snicking occurred in 100% of the birds and mortality reached 50%. CELO (Phelps strain) antiserum neutralized uncloned and cloned CUA-2 in chicken embryos and uncloned virus in chicken embryo fibroblast cell cultures. Quail bronchitis virus antiserum neutralized cloned CUA-2 in TK cells. Agar-gel precipitin lines of identity were formed using CELO antiserum and postinoculation sera from experimentally infected turkeys. Serologically, this virus should be classified as a type-1 adenovirus."} {"id": "PMID:173283", "title": "Enhanced synthesis de novo of phosphatidylinositol in lymphocytes treated with cationic amphiphilic drugs.", "content": "A variety of amphiphilic cations caused very large increases in the rates of incorporation of Pi and glycerol into phosphatidylinositol in pig mesenteric small lymphocytes. This synthesis de novo of phosphatidylinositol led to a doubling of the phosphatidylinositol concentration in the cells within 3.5 h. The increase in synthesis of phosphatidylinositol labelled with [3H]- or [14C]-glycerol was matched by an approximately equivalent decrease in incorporation of glycerol into phosphatidylcholine, phosphatidylethanolamine and triacylglycerol. Amphilic cations which produced these effects included, in order of decreasing effectiveness, trifluoperazine (half-maximal effect at about 70 mum) greater than chlorpromazine approximately promethazine approximately imipramine greater than cinchocaine greater than amethocaine approximately cetyltrimethylammonium greater than fenfluramine greater than amphetamine greater than 2-phenethylamine greater than cocaine approximately procaine; the most effective compounds were those with the largest and most hydrophobic non-polar substituents. The response to cations was not changed by varying the extracellular Ca2+ concentration in the range 10 nm-1mm. The active amphiphilic cations interacted with anionic phospholipids causing aggregation of aqueous dispersions and/or changes in chromatographic behaviour. These results indicate that amphiphilic cations redirect glycerolipid synthesis de novo, probably owing to inhibition of phosphatidate phosphohydrolase, so that phosphatidylinositol synthesis is increased at the expense of other glycerolipids.", "contents": "Enhanced synthesis de novo of phosphatidylinositol in lymphocytes treated with cationic amphiphilic drugs. A variety of amphiphilic cations caused very large increases in the rates of incorporation of Pi and glycerol into phosphatidylinositol in pig mesenteric small lymphocytes. This synthesis de novo of phosphatidylinositol led to a doubling of the phosphatidylinositol concentration in the cells within 3.5 h. The increase in synthesis of phosphatidylinositol labelled with [3H]- or [14C]-glycerol was matched by an approximately equivalent decrease in incorporation of glycerol into phosphatidylcholine, phosphatidylethanolamine and triacylglycerol. Amphilic cations which produced these effects included, in order of decreasing effectiveness, trifluoperazine (half-maximal effect at about 70 mum) greater than chlorpromazine approximately promethazine approximately imipramine greater than cinchocaine greater than amethocaine approximately cetyltrimethylammonium greater than fenfluramine greater than amphetamine greater than 2-phenethylamine greater than cocaine approximately procaine; the most effective compounds were those with the largest and most hydrophobic non-polar substituents. The response to cations was not changed by varying the extracellular Ca2+ concentration in the range 10 nm-1mm. The active amphiphilic cations interacted with anionic phospholipids causing aggregation of aqueous dispersions and/or changes in chromatographic behaviour. These results indicate that amphiphilic cations redirect glycerolipid synthesis de novo, probably owing to inhibition of phosphatidate phosphohydrolase, so that phosphatidylinositol synthesis is increased at the expense of other glycerolipids."} {"id": "PMID:173284", "title": "The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments.", "content": "The possibility that Ca2+ ions are involved in the control of the increased phosphatidylinositol turnover which is provoked by alpha-adrenergic or muscarinic cholinergic stimulation of rat parotid-gland fragments has been investigated. Both types of stimulation provoked phosphatidylinositol breakdown, which was detected either chemically or radiochemically, and provoked a compensatory synthesis of the lipid, detected as an increased rate of incorporation of 32Pi into phosphatidylinositol. Acetylcholine had little effect on the incorporation of labelled glycerol, whereas adrenaline stimulated it significantly, but to a much lower extent than 32P incorporation: this suggests that the response to acetylcholine was entirely accounted for by renewal of the phosphorylinositol head-group of the lipid, but that some synthesis de novo was involved in the response to adrenaline. The responses to both types of stimulation, whether measured as phosphatidylinositol breakdown or as phosphatidylinositol labelling, occurred equally well in incubation media containing 2.5 mm-Ca2+ or 0.2 mm-EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid]. Incubation with a bivalent cation ionophore (A23187) led to a small and more variable increase in phosphatidylinositol labelling with 32Pi, which occurred whether or not Ca2+ was available in the extracellular medium: this was not accompanied by significant phosphatidylinositol breakdown. Cinchocaine, a local anaesthetic, produced parallel increases in the incorporation of Pi and glycerol into phosphatidylinositol. This is compatible with its known ability to inhibit phosphatidate phosphohydrolase (EC 3.1.3.4) and increase phosphatidylinositol synthesis de novo in other cells. These results indicate that the phosphatidylinositol turnover evoked by alpha-adrenergic or muscarinic cholinergic stimuli in rat parotid gland probably does not depend on an influx of Ca2+ into the cells in response to stimulation. This is in marked contrast with the K+ efflux from this tissue, which is controlled by the same receptors, but is strictly dependent on the presence of extracellular Ca2+. The Ca2+-independence of stimulated phosphatidylinositol metabolism may mean that it is controlled through a mode of receptor function different from that which controls other cell responses. Alternatively, it can be interpreted as indicating that stimulated phosphatidylinositol breakdown is intimately involved in the mechanisms of action of alpha-adrenergic and muscarinic cholinergic receptor systems.", "contents": "The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments. The possibility that Ca2+ ions are involved in the control of the increased phosphatidylinositol turnover which is provoked by alpha-adrenergic or muscarinic cholinergic stimulation of rat parotid-gland fragments has been investigated. Both types of stimulation provoked phosphatidylinositol breakdown, which was detected either chemically or radiochemically, and provoked a compensatory synthesis of the lipid, detected as an increased rate of incorporation of 32Pi into phosphatidylinositol. Acetylcholine had little effect on the incorporation of labelled glycerol, whereas adrenaline stimulated it significantly, but to a much lower extent than 32P incorporation: this suggests that the response to acetylcholine was entirely accounted for by renewal of the phosphorylinositol head-group of the lipid, but that some synthesis de novo was involved in the response to adrenaline. The responses to both types of stimulation, whether measured as phosphatidylinositol breakdown or as phosphatidylinositol labelling, occurred equally well in incubation media containing 2.5 mm-Ca2+ or 0.2 mm-EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid]. Incubation with a bivalent cation ionophore (A23187) led to a small and more variable increase in phosphatidylinositol labelling with 32Pi, which occurred whether or not Ca2+ was available in the extracellular medium: this was not accompanied by significant phosphatidylinositol breakdown. Cinchocaine, a local anaesthetic, produced parallel increases in the incorporation of Pi and glycerol into phosphatidylinositol. This is compatible with its known ability to inhibit phosphatidate phosphohydrolase (EC 3.1.3.4) and increase phosphatidylinositol synthesis de novo in other cells. These results indicate that the phosphatidylinositol turnover evoked by alpha-adrenergic or muscarinic cholinergic stimuli in rat parotid gland probably does not depend on an influx of Ca2+ into the cells in response to stimulation. This is in marked contrast with the K+ efflux from this tissue, which is controlled by the same receptors, but is strictly dependent on the presence of extracellular Ca2+. The Ca2+-independence of stimulated phosphatidylinositol metabolism may mean that it is controlled through a mode of receptor function different from that which controls other cell responses. Alternatively, it can be interpreted as indicating that stimulated phosphatidylinositol breakdown is intimately involved in the mechanisms of action of alpha-adrenergic and muscarinic cholinergic receptor systems."} {"id": "PMID:173285", "title": "An investigation of the involvement of adenosine 3':5'-cyclic monophosphate in steroidogenesis by using isolated adrenal cell column perfusion.", "content": "The involvement of cyclic AMP in corticosteroidogenesis was investigated by using isolated adrenal cell column perfusion. Steroids were produced in response to 0.5, 1.0 and 5.0 mg of cyclic AMP/ml. Analysis of the shape of the response curves indicated an inverse relationship between rate of onset of steroid production and dose. A further increase in steroid production during the washout period after the 5 mg/ml dose was considered to indicate an intracellular inhibitory effect of cyclic AMP. Release of cyclic AMP into the perfusate only occurred in response to supramaximal steroidogenic doses of ACTH (adrenocorticotrophin). A connexion between dose and response was demonstrated over a narrow concentration range. Variation in the time-lag before cyclic AMP production and in the duration of the response was marked; further, no reproducible ratio of steroid output to cyclic AMP output was shown at any level of stimulation. These results are discussed together with those of other recent investigations. It is considered that these findings do not support an obligatory role for cyclic AMP as mediator of ACTH action in the adrenal.", "contents": "An investigation of the involvement of adenosine 3':5'-cyclic monophosphate in steroidogenesis by using isolated adrenal cell column perfusion. The involvement of cyclic AMP in corticosteroidogenesis was investigated by using isolated adrenal cell column perfusion. Steroids were produced in response to 0.5, 1.0 and 5.0 mg of cyclic AMP/ml. Analysis of the shape of the response curves indicated an inverse relationship between rate of onset of steroid production and dose. A further increase in steroid production during the washout period after the 5 mg/ml dose was considered to indicate an intracellular inhibitory effect of cyclic AMP. Release of cyclic AMP into the perfusate only occurred in response to supramaximal steroidogenic doses of ACTH (adrenocorticotrophin). A connexion between dose and response was demonstrated over a narrow concentration range. Variation in the time-lag before cyclic AMP production and in the duration of the response was marked; further, no reproducible ratio of steroid output to cyclic AMP output was shown at any level of stimulation. These results are discussed together with those of other recent investigations. It is considered that these findings do not support an obligatory role for cyclic AMP as mediator of ACTH action in the adrenal."} {"id": "PMID:173286", "title": "Proportional activities of glycerol kinase and glycerol 3-phosphate dehydrogenase in rat hepatomas.", "content": "The activities of glycerol 3-phosphate dehydrogenase (EC 1.1.1.8), glycerol kinase (EC 2.7.1.30), lactate dehydrogenase (EC 1.1.1.27), \"malic' enzyme (L-malate-NADP+ oxidoreductase; EC 1.1.1.40) and the beta-oxoacyl-(acyl-carrier protein) reductase component of the fatty acid synthetase complex were measured in nine hepatoma lines (8 in rats, 1 in mouse) and in the livers of host animals. With the single exception of Morris hepatoma 16, which had unusually high glycerol 3-phosphate dehydrogenase activity, the activities of glycerol 3-phosphate dehydrogenase and glycerol kinase were highly correlated in normal livers and hepatomas (r = 0.97; P less than 0.01). The activities of these two enzymes were not strongly correlated with the activities of any of the other three enzymes. The primary function of hepatic glycerol 3-phosphate dehydrogenase appears to be in gluconeogenesis from glycerol.", "contents": "Proportional activities of glycerol kinase and glycerol 3-phosphate dehydrogenase in rat hepatomas. The activities of glycerol 3-phosphate dehydrogenase (EC 1.1.1.8), glycerol kinase (EC 2.7.1.30), lactate dehydrogenase (EC 1.1.1.27), \"malic' enzyme (L-malate-NADP+ oxidoreductase; EC 1.1.1.40) and the beta-oxoacyl-(acyl-carrier protein) reductase component of the fatty acid synthetase complex were measured in nine hepatoma lines (8 in rats, 1 in mouse) and in the livers of host animals. With the single exception of Morris hepatoma 16, which had unusually high glycerol 3-phosphate dehydrogenase activity, the activities of glycerol 3-phosphate dehydrogenase and glycerol kinase were highly correlated in normal livers and hepatomas (r = 0.97; P less than 0.01). The activities of these two enzymes were not strongly correlated with the activities of any of the other three enzymes. The primary function of hepatic glycerol 3-phosphate dehydrogenase appears to be in gluconeogenesis from glycerol."} {"id": "PMID:173287", "title": "The stimulation of the phospholipase A2-acylation system of synaptic membranes of brain by cyclic nucleotides.", "content": "Hydrolysis of phosphatidylcholine by phospholipase A2 of synaptic membranes i n Tris-CHl buffer was stimulated by cyclic AMP, cyclic GMP, cyclic CMP, cyclic UMP and adenosine (0.1 mm). In the presence of 1 mm-NaF and cofactors, the same cyclic nucleotides and adenosine (10 mm) stimulated the incorporation of added oleate into the choline glycerophospholipids of synaptic membranes. Cyclic AMP and noradrenaline stimulated the incorporation of added oleate into position 2 of choline glycerophospholipid. Stimulation of net acylation was increased by preincubation in conditions which stimulated hydrolysis of phosphatidylcholine. Cyclic AMP only slightly stimulated the transfer of oleate from oleoyl-CoA into choline glycerophospholipid. The optimum concentration of CaCl2 for the stimulation of hydrolysis by phospholipase A2 by cyclic AMP was 1 mum. Stimulation of the incorporation of added oleate was maximal in the CaCl2 concentration range 1 mum-1mm. MgCl2 also enhanced stimulations, maximum effects being obtained with concentrations of 10 mum and 0.5 mm for hydrolysis by phospholipase A2 and incorporation of added oleate respectively. ATP enhanced the stimulation of incorporation of oleate but had no effect on the cyclic nucleotide stimulation of hydrolysis of added phosphatidylcholine by phospholipase A2. Adenosine, guanosine, ADP and 5'-AMP (all at 1 mm) inhibited the stimulation of incorporation of oleate by cyclic nucleotides and inhibited the transfer of oleate from oleoyl-CoA to phospholipid. They did not inhibit the stimulation of hydrolysis of added phosphatidylcholine (by phospholipase A2) by cyclic nucleotides, but inhibited the stimulation by noradrenaline, acetylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine) and histamine. Preincubation of synaptic membranes in the water or buffer increased the net activity of phospholipase A2. Preincubation with a mixture of ATP and MgCl2 increased the initial rate of acylation of membrane lipid.", "contents": "The stimulation of the phospholipase A2-acylation system of synaptic membranes of brain by cyclic nucleotides. Hydrolysis of phosphatidylcholine by phospholipase A2 of synaptic membranes i n Tris-CHl buffer was stimulated by cyclic AMP, cyclic GMP, cyclic CMP, cyclic UMP and adenosine (0.1 mm). In the presence of 1 mm-NaF and cofactors, the same cyclic nucleotides and adenosine (10 mm) stimulated the incorporation of added oleate into the choline glycerophospholipids of synaptic membranes. Cyclic AMP and noradrenaline stimulated the incorporation of added oleate into position 2 of choline glycerophospholipid. Stimulation of net acylation was increased by preincubation in conditions which stimulated hydrolysis of phosphatidylcholine. Cyclic AMP only slightly stimulated the transfer of oleate from oleoyl-CoA into choline glycerophospholipid. The optimum concentration of CaCl2 for the stimulation of hydrolysis by phospholipase A2 by cyclic AMP was 1 mum. Stimulation of the incorporation of added oleate was maximal in the CaCl2 concentration range 1 mum-1mm. MgCl2 also enhanced stimulations, maximum effects being obtained with concentrations of 10 mum and 0.5 mm for hydrolysis by phospholipase A2 and incorporation of added oleate respectively. ATP enhanced the stimulation of incorporation of oleate but had no effect on the cyclic nucleotide stimulation of hydrolysis of added phosphatidylcholine by phospholipase A2. Adenosine, guanosine, ADP and 5'-AMP (all at 1 mm) inhibited the stimulation of incorporation of oleate by cyclic nucleotides and inhibited the transfer of oleate from oleoyl-CoA to phospholipid. They did not inhibit the stimulation of hydrolysis of added phosphatidylcholine (by phospholipase A2) by cyclic nucleotides, but inhibited the stimulation by noradrenaline, acetylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine) and histamine. Preincubation of synaptic membranes in the water or buffer increased the net activity of phospholipase A2. Preincubation with a mixture of ATP and MgCl2 increased the initial rate of acylation of membrane lipid."} {"id": "PMID:173288", "title": "Regulation of carbohydrate metabolism in lymphoid tissue. Quantitative aspects of [U-14C]glucose oxidation by rat spleen slices.", "content": "When washed spleen slices from fed rats are incubated with 3 mm-[U-14C]glucose, the rate of glucose utilization (46.2 mumol/h per g dry wt.) is sufficient to account, theoretically, for 80% of the O2 consumption. Measurement of net lactate production, however, and the fate of the radioactive carbon, indicates that the contribution of glucose to the respiratory fuel of the tissue is only 25-30% whereas 60-70% of the glucose utilized is converted into lactate. At saturating glucose concentrations (above 5 mm) its contribution to the respiratory fuel of the slice is increased to a maximum value of 34-39%. Only 2% of the glucose utilized is metabolized via the oxidative steps of the pentose phosphate pathway. Starvation for 72 h marginally increases both the rate of glucose utilization (by 21%) and its net contribution to the respiratory fuel (by 29%). Insulin, glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate have no significant effect on either the rate of glucose utilization or on the pattern of radioactive isotope distribution. The uptake of glucose is increased by only 20%, whereas the production of lactate doubles when slices are incubated under anaerobic conditions. In assessing the suitability of spleen slices for metabolic studies, the only serious major perturbation, compared with the freeze-clamped organ, is an elevated mitochondrial [NAD+]/[NADH] ratio (connected with increased endogenous NH3 production) that is partially restored to normal values on incubation with glucose. Equal proportions of erythrocytes and leucocytes are found in the washed spleen slice. Metabolic contributions of the constituent cell populations in the washed slice are calculated and it is concluded that lymphocytes account for the major part of the glycolytic metabolism (80-90%), whereas the contribution of erythrocytes is insignificant.", "contents": "Regulation of carbohydrate metabolism in lymphoid tissue. Quantitative aspects of [U-14C]glucose oxidation by rat spleen slices. When washed spleen slices from fed rats are incubated with 3 mm-[U-14C]glucose, the rate of glucose utilization (46.2 mumol/h per g dry wt.) is sufficient to account, theoretically, for 80% of the O2 consumption. Measurement of net lactate production, however, and the fate of the radioactive carbon, indicates that the contribution of glucose to the respiratory fuel of the tissue is only 25-30% whereas 60-70% of the glucose utilized is converted into lactate. At saturating glucose concentrations (above 5 mm) its contribution to the respiratory fuel of the slice is increased to a maximum value of 34-39%. Only 2% of the glucose utilized is metabolized via the oxidative steps of the pentose phosphate pathway. Starvation for 72 h marginally increases both the rate of glucose utilization (by 21%) and its net contribution to the respiratory fuel (by 29%). Insulin, glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate have no significant effect on either the rate of glucose utilization or on the pattern of radioactive isotope distribution. The uptake of glucose is increased by only 20%, whereas the production of lactate doubles when slices are incubated under anaerobic conditions. In assessing the suitability of spleen slices for metabolic studies, the only serious major perturbation, compared with the freeze-clamped organ, is an elevated mitochondrial [NAD+]/[NADH] ratio (connected with increased endogenous NH3 production) that is partially restored to normal values on incubation with glucose. Equal proportions of erythrocytes and leucocytes are found in the washed spleen slice. Metabolic contributions of the constituent cell populations in the washed slice are calculated and it is concluded that lymphocytes account for the major part of the glycolytic metabolism (80-90%), whereas the contribution of erythrocytes is insignificant."} {"id": "PMID:173289", "title": "The effects of adenine nucleotides and guanine nucleotides on urate synthesis de novo by isolated chick liver and kidney cells.", "content": "Isolated chick liver and kidney cells produce urate de novo from glycine, and this is partially inhibited by 1 mm-AMP and by 1 mm-GMP in liver cells but not in kidney cells. Azaserine fully inhibits this synthesis de novo, but attempts to isolate formylglycine amide ribonucleotide from azaserine-blocked cells were unsuccessful.", "contents": "The effects of adenine nucleotides and guanine nucleotides on urate synthesis de novo by isolated chick liver and kidney cells. Isolated chick liver and kidney cells produce urate de novo from glycine, and this is partially inhibited by 1 mm-AMP and by 1 mm-GMP in liver cells but not in kidney cells. Azaserine fully inhibits this synthesis de novo, but attempts to isolate formylglycine amide ribonucleotide from azaserine-blocked cells were unsuccessful."} {"id": "PMID:173290", "title": "The phosphorylation of troponin I from cardiac muscle.", "content": "1. Troponin I isolated from fresh cardiac muscle by affinity chromatography contains about 1.9 mol of covalently bound phosphate/mol. Similar preparations of white-skeletal-muscle troponin I contain about 0.5 mol of phosphate/mol. 2. A 3':5'-cyclic AMP-dependent protein kinase and a protein phosphatase are associated with troponin isolated from cardiac muscle. 3. Bovine cardiac 3':5'-cyclic AMP-dependent protein kinase catalyses the phosphorylation of cardiac troponin I 30 times faster than white-skeletal-muscle troponin I. 4. Troponin I is the only component of cardiac troponin phosphorylated at a significant rate by the endogenous or a bovine cardiac 3':5'-cyclic AMP-dependent protein kinase. 5. Phosphorylase kinase catalyses the phosphorylation of cardiac troponin I at similar or slightly faster rates than white-skeletal-muscle troponin I. 6. Troponin C inhibits the phosphorylation of cardiac and skeletal troponin I catalysed by phosphorylase kinase and the phosphorylation of white skeletal troponin I catalysed by 3':5'-cyclic AMP-dependent protein kinase; the phosphorylation of cardiac troponin I catalysed by the latter enzyme is not inhibited.", "contents": "The phosphorylation of troponin I from cardiac muscle. 1. Troponin I isolated from fresh cardiac muscle by affinity chromatography contains about 1.9 mol of covalently bound phosphate/mol. Similar preparations of white-skeletal-muscle troponin I contain about 0.5 mol of phosphate/mol. 2. A 3':5'-cyclic AMP-dependent protein kinase and a protein phosphatase are associated with troponin isolated from cardiac muscle. 3. Bovine cardiac 3':5'-cyclic AMP-dependent protein kinase catalyses the phosphorylation of cardiac troponin I 30 times faster than white-skeletal-muscle troponin I. 4. Troponin I is the only component of cardiac troponin phosphorylated at a significant rate by the endogenous or a bovine cardiac 3':5'-cyclic AMP-dependent protein kinase. 5. Phosphorylase kinase catalyses the phosphorylation of cardiac troponin I at similar or slightly faster rates than white-skeletal-muscle troponin I. 6. Troponin C inhibits the phosphorylation of cardiac and skeletal troponin I catalysed by phosphorylase kinase and the phosphorylation of white skeletal troponin I catalysed by 3':5'-cyclic AMP-dependent protein kinase; the phosphorylation of cardiac troponin I catalysed by the latter enzyme is not inhibited."} {"id": "PMID:173291", "title": "Electron-paramagnetic-resonance spectroscopy of iron-binding fragments of hen ovotransferrins.", "content": "1. It is confirmed that there are two e.p.r. (electron-paramagnetic-resonance) signals associated with fully loaded ovotransferrin, which has two iron-binding sites. 2. Through experiments in which either of the two sites of whole ovotransferrin is occupied, the other being empty, the first occupied site is shown to belong to the N-terminal region of the protein; the second occupied site is in the C-terminal region. 3. When the protein is cleaved with trypsin or subtilisin, the N-terminal fragments are spectroscopically similar to the monoferric ovotransferrin complexes in which the iron atom occupies the N-terminal or C-terminal site respectively. Each fragment displays the same two e.p.r. signals, though not in the same proportions. 4. Computer summations of the e.p.r. spectra confirm that there is no iron-iron interaction which affects the spin Hamiltonian parameters at the iron-binding sites.", "contents": "Electron-paramagnetic-resonance spectroscopy of iron-binding fragments of hen ovotransferrins. 1. It is confirmed that there are two e.p.r. (electron-paramagnetic-resonance) signals associated with fully loaded ovotransferrin, which has two iron-binding sites. 2. Through experiments in which either of the two sites of whole ovotransferrin is occupied, the other being empty, the first occupied site is shown to belong to the N-terminal region of the protein; the second occupied site is in the C-terminal region. 3. When the protein is cleaved with trypsin or subtilisin, the N-terminal fragments are spectroscopically similar to the monoferric ovotransferrin complexes in which the iron atom occupies the N-terminal or C-terminal site respectively. Each fragment displays the same two e.p.r. signals, though not in the same proportions. 4. Computer summations of the e.p.r. spectra confirm that there is no iron-iron interaction which affects the spin Hamiltonian parameters at the iron-binding sites."} {"id": "PMID:173292", "title": "Oxidase-peroxidase enzymes of Datura innoxia. Oxidation of reduced nicotinamide-adenine dinucleotide in the presence of formylphenylacetic acid ethyl ester.", "content": "The oxidase-peroxidase from Datura innoxia which catalyses the oxidation of formylphenylacetic acid ethyl ester to benzoylformic acid ethyl ester and formic acid was also found to catalyse the oxidation of NADH in the presence of Mn2+ and formylphenylacetic acid ethyl ester. NADH was not oxidized in the absence of formylphenylacetic acid ethyl ester, although formylphenylacetonitrile or phenylacetaldehyde could replace it in the reaction. The reaction appeared to be complex and for every mol of NADH oxidized 3-4 g-atoms of oxygen were utilized, with a concomitant formation of approx. 0.8 mol of H2O2, the latter being identified by the starch-iodide test and decomposition by catalase. Benzoylformic acid ethyl ester was also formed in the reaction, but in a nonlinear fashion, indicating a lag phase. In the absence of Mn2+, NADH oxidation was not only very low, but itself inhibited the formation of benzoylformic acid ethyl ester from formylphenylacetic acid ethyl ester. A reaction mechanism for the oxidation of NADH in the presence of formylphenylacetic acid ethyl ester is proposed.", "contents": "Oxidase-peroxidase enzymes of Datura innoxia. Oxidation of reduced nicotinamide-adenine dinucleotide in the presence of formylphenylacetic acid ethyl ester. The oxidase-peroxidase from Datura innoxia which catalyses the oxidation of formylphenylacetic acid ethyl ester to benzoylformic acid ethyl ester and formic acid was also found to catalyse the oxidation of NADH in the presence of Mn2+ and formylphenylacetic acid ethyl ester. NADH was not oxidized in the absence of formylphenylacetic acid ethyl ester, although formylphenylacetonitrile or phenylacetaldehyde could replace it in the reaction. The reaction appeared to be complex and for every mol of NADH oxidized 3-4 g-atoms of oxygen were utilized, with a concomitant formation of approx. 0.8 mol of H2O2, the latter being identified by the starch-iodide test and decomposition by catalase. Benzoylformic acid ethyl ester was also formed in the reaction, but in a nonlinear fashion, indicating a lag phase. In the absence of Mn2+, NADH oxidation was not only very low, but itself inhibited the formation of benzoylformic acid ethyl ester from formylphenylacetic acid ethyl ester. A reaction mechanism for the oxidation of NADH in the presence of formylphenylacetic acid ethyl ester is proposed."} {"id": "PMID:173293", "title": "Ox liver glutamate dehydrogenase. The role of lysine-126 reappraised in the light of studies of inhibition and inactivation by pyridoxal 5'-phosphate.", "content": "The time-course of inactivation of bovine liver glutamate dehydrogenase by pyridoxal 5'-phosphate was studied in the presence of varied amounts of 2-oxoglutarate or NADH. Pseudo-first-order analysis reveals that the protection by both these compounds is competitive with respect to the chemical modifier. The competition is only partial, however: saturation with either NADH or 2-oxoglutarate decreases the rate constant for inactivation to a finite minimum and not to zero. Similarly, the plot of activity at equilibrium as a function of the concentration of the protecting substrate or coenzyme reveals that neither NADH nor 2-oxoglutarate protects completely against inactivation. In initial-rate experiments, pyridoxal 5'-phosphate, used as an instantaneous inhibitor rather than a long-term inactivator, displayed non-competitive inhibition with respect to both 2-oxoglutarate and NADH. These results clearly indicate that, although there is mutual hindrance between the binding to the enzyme of pyridoxal 5'-phosphate, on the one hand, and 2-oxoglutarate or NADH on the other, binding is not mutually exclusive. These findings are discussed in terms of the two-step mechanism for inactivation by pyridoxal 5'-phosphate. It is concluded that lysine-126 cannot be solely responsible for binding either the substrate or the coenzyme, but could be essential for the catalytic step.", "contents": "Ox liver glutamate dehydrogenase. The role of lysine-126 reappraised in the light of studies of inhibition and inactivation by pyridoxal 5'-phosphate. The time-course of inactivation of bovine liver glutamate dehydrogenase by pyridoxal 5'-phosphate was studied in the presence of varied amounts of 2-oxoglutarate or NADH. Pseudo-first-order analysis reveals that the protection by both these compounds is competitive with respect to the chemical modifier. The competition is only partial, however: saturation with either NADH or 2-oxoglutarate decreases the rate constant for inactivation to a finite minimum and not to zero. Similarly, the plot of activity at equilibrium as a function of the concentration of the protecting substrate or coenzyme reveals that neither NADH nor 2-oxoglutarate protects completely against inactivation. In initial-rate experiments, pyridoxal 5'-phosphate, used as an instantaneous inhibitor rather than a long-term inactivator, displayed non-competitive inhibition with respect to both 2-oxoglutarate and NADH. These results clearly indicate that, although there is mutual hindrance between the binding to the enzyme of pyridoxal 5'-phosphate, on the one hand, and 2-oxoglutarate or NADH on the other, binding is not mutually exclusive. These findings are discussed in terms of the two-step mechanism for inactivation by pyridoxal 5'-phosphate. It is concluded that lysine-126 cannot be solely responsible for binding either the substrate or the coenzyme, but could be essential for the catalytic step."} {"id": "PMID:173294", "title": "Horse liver alcohol dehydrogenase. A study of the essential lysine residue.", "content": "1. The inactivation of horse liver alcohol dehydrogenase by pyridoxal 5'-phosphate in phosphate buffer, pH8, at 10 degrees C was investigated. Activity declines to a minimum value determined by the pyridoxal 5'-phosphate concentration. The maximum inactivation in a single treatment is 75%. This limit appears to be set by the ratio of the first-order rate constants for interconversion of inactive covalently modified enzyme and a readily dissociable non-covalent enzyme-modifier complex. 2. Reactivation was virtually complete on 150-fold dilution: first-order analysis yielded an estimate of the rate constant (0.164min-1), which was then used in the kinetic analysis of the forward inactivation reaction. This provided estimates for the rate constant for conversion of non-covalent complex into inactive enzyme (0.465 min-1) and the dissociation constant of the non-covalent complex (2.8 mM). From the two first-order constants, the minimum attainable activity in a single cycle of treatment may be calculated as 24.5%, very close to the observed value. 3. Successive cycles of modification followed by reduction with NaBH4 each decreased activity by the same fraction, so that three cycles with 3.6 mM-pyridoxal 5'-phosphate decreased specific activity to about 1% of the original value. The absorption spectrum of the enzyme thus treated indicated incorporation of 2-3 mol of pyridoxal 5'-phosphate per mol of subunit, covalently bonded to lysine residues. 4. NAD+ and NADH protected the enzyme completely against inactivation by pyridoxal 5'-phosphate, but ethanol and acetaldehyde were without effect. 5. Pyridoxal 5'-phosphate used as an inhibitor in steady-state experiments, rather than as an inactivator, was non-competitive with respect to both NADH and acetaldehyde. 6. The partially modified enzyme (74% inactive) showed unaltered apparent Km values for NAD+ and ethanol, indicating that modified enzyme is completely inactive, and that the residual activity is due to enzyme that has not been covalently modified. 7. Activation by methylation with formaldehyde was confirmed, but this treatment does not prevent subsequent inactivation with pyridoxal 5'-phosphate. Presumably different lysine residues are involved. 8. It is likely that the essential lysine residue modified by pyridoxal 5'-phosphate is involved either in binding the coenzymes or in the catalytic step. 9. Less detailed studies of yeast alcohol dehydrogenase suggest that this enzyme also possesses an essential lysine residue.", "contents": "Horse liver alcohol dehydrogenase. A study of the essential lysine residue. 1. The inactivation of horse liver alcohol dehydrogenase by pyridoxal 5'-phosphate in phosphate buffer, pH8, at 10 degrees C was investigated. Activity declines to a minimum value determined by the pyridoxal 5'-phosphate concentration. The maximum inactivation in a single treatment is 75%. This limit appears to be set by the ratio of the first-order rate constants for interconversion of inactive covalently modified enzyme and a readily dissociable non-covalent enzyme-modifier complex. 2. Reactivation was virtually complete on 150-fold dilution: first-order analysis yielded an estimate of the rate constant (0.164min-1), which was then used in the kinetic analysis of the forward inactivation reaction. This provided estimates for the rate constant for conversion of non-covalent complex into inactive enzyme (0.465 min-1) and the dissociation constant of the non-covalent complex (2.8 mM). From the two first-order constants, the minimum attainable activity in a single cycle of treatment may be calculated as 24.5%, very close to the observed value. 3. Successive cycles of modification followed by reduction with NaBH4 each decreased activity by the same fraction, so that three cycles with 3.6 mM-pyridoxal 5'-phosphate decreased specific activity to about 1% of the original value. The absorption spectrum of the enzyme thus treated indicated incorporation of 2-3 mol of pyridoxal 5'-phosphate per mol of subunit, covalently bonded to lysine residues. 4. NAD+ and NADH protected the enzyme completely against inactivation by pyridoxal 5'-phosphate, but ethanol and acetaldehyde were without effect. 5. Pyridoxal 5'-phosphate used as an inhibitor in steady-state experiments, rather than as an inactivator, was non-competitive with respect to both NADH and acetaldehyde. 6. The partially modified enzyme (74% inactive) showed unaltered apparent Km values for NAD+ and ethanol, indicating that modified enzyme is completely inactive, and that the residual activity is due to enzyme that has not been covalently modified. 7. Activation by methylation with formaldehyde was confirmed, but this treatment does not prevent subsequent inactivation with pyridoxal 5'-phosphate. Presumably different lysine residues are involved. 8. It is likely that the essential lysine residue modified by pyridoxal 5'-phosphate is involved either in binding the coenzymes or in the catalytic step. 9. Less detailed studies of yeast alcohol dehydrogenase suggest that this enzyme also possesses an essential lysine residue."} {"id": "PMID:173295", "title": "Kinetic studies on (N-formyltryptophyl)cytochrome c.", "content": "The formylation of the ring nitrogen atom of the tryptophan residue in cytochrome c was carried out and consequent changes in the kinetic properties of the protein were investigated. The reduction of formylated cytochrome c by Cr2+ was studied by stopped-flow techniques. At pH 6.5 the reduction process shows the presence of two phases. One phase (k = 4 X 10(4) M-1-s-1) is dependent on Cr2+ concentration and one phase (k = 5.0 s-1) is not. A study of the temperature dependence of the two phases yields values for their activation energies of 38.6kJ-mol-1 and 42.4kJ-mol-1 respectively. The reaction of the reduced formylated cytochrome c with CO was followed by means of both stopped-flow techniques and flash photolysis. The combination with CO at pH 6.8 measured in stopped-flow experiments shows two phases, both dependent on the concentration of CO (k1 = 1.8 X 10(2) M-1-s-1). If CO was dissociated from the protein by photolysis and then allowed to recombine with it, it was found to do so in a simple manner, at a rate which depended on the concentration of CO (k = 1.9 X 10(2) M-1-s-1). A tentative model which can accommodate these findings is proposed. The reaction of the oxidized form of formylated cytochrome c with NO was followed by means of stopped-flow techniques. The reaction was found to be biphasic with one phase dependent on the concentration of NO (k = 2.8 X 10(3) M-1-s-1) and one phase (k = 0.2x-1) independent of the concentration of NO. This behaviour is compared with that of the native molecule. A comparison of these kinetic observations with those on other tryptophan-specific modifications leads to the conclusion that the main alteration in kinetic properties is due, not to the nature of the modifying group, but rather to the disruption of the normal environment of the haem.", "contents": "Kinetic studies on (N-formyltryptophyl)cytochrome c. The formylation of the ring nitrogen atom of the tryptophan residue in cytochrome c was carried out and consequent changes in the kinetic properties of the protein were investigated. The reduction of formylated cytochrome c by Cr2+ was studied by stopped-flow techniques. At pH 6.5 the reduction process shows the presence of two phases. One phase (k = 4 X 10(4) M-1-s-1) is dependent on Cr2+ concentration and one phase (k = 5.0 s-1) is not. A study of the temperature dependence of the two phases yields values for their activation energies of 38.6kJ-mol-1 and 42.4kJ-mol-1 respectively. The reaction of the reduced formylated cytochrome c with CO was followed by means of both stopped-flow techniques and flash photolysis. The combination with CO at pH 6.8 measured in stopped-flow experiments shows two phases, both dependent on the concentration of CO (k1 = 1.8 X 10(2) M-1-s-1). If CO was dissociated from the protein by photolysis and then allowed to recombine with it, it was found to do so in a simple manner, at a rate which depended on the concentration of CO (k = 1.9 X 10(2) M-1-s-1). A tentative model which can accommodate these findings is proposed. The reaction of the oxidized form of formylated cytochrome c with NO was followed by means of stopped-flow techniques. The reaction was found to be biphasic with one phase dependent on the concentration of NO (k = 2.8 X 10(3) M-1-s-1) and one phase (k = 0.2x-1) independent of the concentration of NO. This behaviour is compared with that of the native molecule. A comparison of these kinetic observations with those on other tryptophan-specific modifications leads to the conclusion that the main alteration in kinetic properties is due, not to the nature of the modifying group, but rather to the disruption of the normal environment of the haem."} {"id": "PMID:173296", "title": "A pitfall in the interpretation of data on ligand-protein interaction.", "content": "Binding reactions are usually investigated by separation of free and bound labelled ligand. Underestimation of the amount bound leads to inaccurate estimation of the dissociation constant and to wrong conclusions on the validity of the model of binding. The activation of cyclic AMP-dependent protein kinase is treated as an example.", "contents": "A pitfall in the interpretation of data on ligand-protein interaction. Binding reactions are usually investigated by separation of free and bound labelled ligand. Underestimation of the amount bound leads to inaccurate estimation of the dissociation constant and to wrong conclusions on the validity of the model of binding. The activation of cyclic AMP-dependent protein kinase is treated as an example."} {"id": "PMID:173297", "title": "Metabolic regulation of beta-galactosidase synthesis in Escherichia coli. A test for constitutive ribosome synthesis.", "content": "The rate of differential synthesis of beta-galactosidase (alphalac) was measured in maximally induced cultures of Escherichia coli B/r with 0.01 M-inducer and 0.01 M-cyclic AMP. The value of alphalac decreases with growth rate (60% between 0.67 and 2.1 doublings/h) and after a nutritional shift-up. This decrease is presumed to reflect a decrease in the intracellular concentration of free active RNA polymerase after a shift-up, which implies that the increase in ribosome synthesis after a shift-up is due to an active induction of the ribosomal components.", "contents": "Metabolic regulation of beta-galactosidase synthesis in Escherichia coli. A test for constitutive ribosome synthesis. The rate of differential synthesis of beta-galactosidase (alphalac) was measured in maximally induced cultures of Escherichia coli B/r with 0.01 M-inducer and 0.01 M-cyclic AMP. The value of alphalac decreases with growth rate (60% between 0.67 and 2.1 doublings/h) and after a nutritional shift-up. This decrease is presumed to reflect a decrease in the intracellular concentration of free active RNA polymerase after a shift-up, which implies that the increase in ribosome synthesis after a shift-up is due to an active induction of the ribosomal components."} {"id": "PMID:173298", "title": "Utilization of gluconate by Escherichia coli. A role of adenosine 3':5'-cyclic monophosphate in the induction of gluconate catabolism.", "content": "1. Cultures of Escherichia coli growing on gluconate use both gluconate and glucose when glucose is added. 2. Glycerol-grown cells adapt to gluconate utilization even in media containing glucose as well as gluconate. 3. The rates of gluconate utilization by cells growing on a mixture of glucose and gluconate, and the specific activities of the gluconate uptake system and of gluconate kinase, are greater if adenosine 3':5'-cyclic monophosphate (cyclic AMP) is present in the medium than in its absence. 4. Growth on media containing gluconate and cyclic AMP is accompanied by the formation of methyl glyoxal and pyruvate, and progressive inhibition of growth. 5. A mutant devoid of adenylate cyclase activity (cya) grew well on glucose in the absence of exogenous cyclic AMP but grew only poorly on gluconate; neither the gluconate uptake system nor gluconate kinase was adequately induced. The addition of cyclic AMP promoted growth on gluconate and facilitated the induction of proteins required for gluconate catabolism. 6. Phage Pl-mediated transduction of cya+ into the cya-mutant also restored the wild-type phenotype in its ability to adapt to gluconate utilization.", "contents": "Utilization of gluconate by Escherichia coli. A role of adenosine 3':5'-cyclic monophosphate in the induction of gluconate catabolism. 1. Cultures of Escherichia coli growing on gluconate use both gluconate and glucose when glucose is added. 2. Glycerol-grown cells adapt to gluconate utilization even in media containing glucose as well as gluconate. 3. The rates of gluconate utilization by cells growing on a mixture of glucose and gluconate, and the specific activities of the gluconate uptake system and of gluconate kinase, are greater if adenosine 3':5'-cyclic monophosphate (cyclic AMP) is present in the medium than in its absence. 4. Growth on media containing gluconate and cyclic AMP is accompanied by the formation of methyl glyoxal and pyruvate, and progressive inhibition of growth. 5. A mutant devoid of adenylate cyclase activity (cya) grew well on glucose in the absence of exogenous cyclic AMP but grew only poorly on gluconate; neither the gluconate uptake system nor gluconate kinase was adequately induced. The addition of cyclic AMP promoted growth on gluconate and facilitated the induction of proteins required for gluconate catabolism. 6. Phage Pl-mediated transduction of cya+ into the cya-mutant also restored the wild-type phenotype in its ability to adapt to gluconate utilization."} {"id": "PMID:173299", "title": "Regulation of citrate synthase activity in methylotrophs by reduced nicotinamide-adenine dinucleotide, adenine nucleotides and 2-oxoglutarate.", "content": "Citrate synthase from two typical facultative methylotrophs, but not from four obligate methylotrophs or from two restricted facultative methylotrophs, is inhibited by 0.1 mM-NADH. ATP or ADP (both at 10mM) inhibits all the citrate synthases, whereas 2-oxoglutarate (10mM) inhibits those from only three of the eight methylotrophs.", "contents": "Regulation of citrate synthase activity in methylotrophs by reduced nicotinamide-adenine dinucleotide, adenine nucleotides and 2-oxoglutarate. Citrate synthase from two typical facultative methylotrophs, but not from four obligate methylotrophs or from two restricted facultative methylotrophs, is inhibited by 0.1 mM-NADH. ATP or ADP (both at 10mM) inhibits all the citrate synthases, whereas 2-oxoglutarate (10mM) inhibits those from only three of the eight methylotrophs."} {"id": "PMID:173300", "title": "Subcellular localization of superoxide dismutase in rat liver.", "content": "The subcellular localization of superoxide dismutase was investigated in rat liver homogenates. Most of the superoxide dismutase activity is present in the soluble fraction (84%), the rest being associated with mitochondria. No indications for the occurrence of superoxide dismutase in other subcellular structures, particularly in peroxisomes, was found. Mitochondrial activity is not due to adsorption, since the sedimentable activity is essentially latent. Subfractionation of mitochondria by hypo-osmotic shock and sonication shows that half of the mitochondrial superoxide dismutase activity is localized in the intermembrane space, the rest of the enzyme being a component of the matrix space. In non-ionic media the matrix enzyme is, however, adsorbed to the inner membrane, from which it can be desorbed by low (0.04M) concentration of KCl. Superoxide dismutase activity was found in all rat organs investigated. Maximal activity of the enzyme is observed in liver, adrenals and kidney. In adrenals, the highest specific activity is associated with the medulla.", "contents": "Subcellular localization of superoxide dismutase in rat liver. The subcellular localization of superoxide dismutase was investigated in rat liver homogenates. Most of the superoxide dismutase activity is present in the soluble fraction (84%), the rest being associated with mitochondria. No indications for the occurrence of superoxide dismutase in other subcellular structures, particularly in peroxisomes, was found. Mitochondrial activity is not due to adsorption, since the sedimentable activity is essentially latent. Subfractionation of mitochondria by hypo-osmotic shock and sonication shows that half of the mitochondrial superoxide dismutase activity is localized in the intermembrane space, the rest of the enzyme being a component of the matrix space. In non-ionic media the matrix enzyme is, however, adsorbed to the inner membrane, from which it can be desorbed by low (0.04M) concentration of KCl. Superoxide dismutase activity was found in all rat organs investigated. Maximal activity of the enzyme is observed in liver, adrenals and kidney. In adrenals, the highest specific activity is associated with the medulla."} {"id": "PMID:173302", "title": "Influence of anti-oestrogens on the specific binding in vitro of (3H)oestradiol by cytosol of rat mammary tumours and human breast carcinomata.", "content": "The anti-oestrogenic potential of two nitrogen-mustard-containing compounds, I.C.I. 79792 and I.C.I. 85966, was studied. I.C.I. 85966 usually did not decrease specific binding of [3H]oestradiol by breast-tumour cytoplasmic proteins. I.C.I. 79792 decreased specific [3H]oestradiol binding, but not to the same extent as similar concentrations of I.C.I. 46474, diethylstilboestrol or dibutyldihydrostilboestrol.", "contents": "Influence of anti-oestrogens on the specific binding in vitro of (3H)oestradiol by cytosol of rat mammary tumours and human breast carcinomata. The anti-oestrogenic potential of two nitrogen-mustard-containing compounds, I.C.I. 79792 and I.C.I. 85966, was studied. I.C.I. 85966 usually did not decrease specific binding of [3H]oestradiol by breast-tumour cytoplasmic proteins. I.C.I. 79792 decreased specific [3H]oestradiol binding, but not to the same extent as similar concentrations of I.C.I. 46474, diethylstilboestrol or dibutyldihydrostilboestrol."} {"id": "PMID:173301", "title": "Stimulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) activity by low concentrations of circulating glucose in perfused rat liver.", "content": "1. After nicotinic acid treatment, rat liver glycogen is depleted and phosphoenolpyruvate carboxykinase activity increased, to about twice the initial value. 2. The increase in phosphoenolpyruvate carboxykinase activity promoted by nicotinic acid is prevented by cycloheximide or actinomycin D, suggesting that this effect is produced by synthesis of the enzyme de novo. 3. Despite the enhancement of phosphoenolpyruvate carboxykinase activity and glycogen depletion, which occurs 5h after the injection of nicotinic acid, the gluconeogenic capacity of liver is low and considerably less than the values found in rats starved for 48h. 4. When the livers of well-fed rats are perfused in the presence of low concentrations of glucose, the activity of phosphoenolpyruvate carboxykinase significantly increases compared with the control. 5. This increase is not related to the glycogen content, but seems to be also the result of synthesis of the enzyme de novo, since this effect is counteracted by previous treatment with cycloheximide or actinomycin D. 6. Phosphoenolpyruvate carboxykinase activity is not increased in the presence of low concentrations of circulating glucose when 40 mM-imidazole (an activator of phosphodiesterase) is added to the perfusion medium. 7. Addition of dibutyryl cyclic AMP to the perfusion medium results in an increase in phosphoenolpyruvate carboxykinase activity, in spite of the presence of normal concentrations of circulating glucose. On the other hand, the concentration of cyclic AMP in the liver increases when that of glucose in the medium is low. 8. These results suggest that, in the absence of hormonal factors, the regulation of phosphoenolpyruvate carboxykinase can be accomplished by glucose itself, inadequate concentrations of it resulting in the induction of the enzyme. The mediator in this regulation, as in hormonal regulation, seems to be cyclic AMP.", "contents": "Stimulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) activity by low concentrations of circulating glucose in perfused rat liver. 1. After nicotinic acid treatment, rat liver glycogen is depleted and phosphoenolpyruvate carboxykinase activity increased, to about twice the initial value. 2. The increase in phosphoenolpyruvate carboxykinase activity promoted by nicotinic acid is prevented by cycloheximide or actinomycin D, suggesting that this effect is produced by synthesis of the enzyme de novo. 3. Despite the enhancement of phosphoenolpyruvate carboxykinase activity and glycogen depletion, which occurs 5h after the injection of nicotinic acid, the gluconeogenic capacity of liver is low and considerably less than the values found in rats starved for 48h. 4. When the livers of well-fed rats are perfused in the presence of low concentrations of glucose, the activity of phosphoenolpyruvate carboxykinase significantly increases compared with the control. 5. This increase is not related to the glycogen content, but seems to be also the result of synthesis of the enzyme de novo, since this effect is counteracted by previous treatment with cycloheximide or actinomycin D. 6. Phosphoenolpyruvate carboxykinase activity is not increased in the presence of low concentrations of circulating glucose when 40 mM-imidazole (an activator of phosphodiesterase) is added to the perfusion medium. 7. Addition of dibutyryl cyclic AMP to the perfusion medium results in an increase in phosphoenolpyruvate carboxykinase activity, in spite of the presence of normal concentrations of circulating glucose. On the other hand, the concentration of cyclic AMP in the liver increases when that of glucose in the medium is low. 8. These results suggest that, in the absence of hormonal factors, the regulation of phosphoenolpyruvate carboxykinase can be accomplished by glucose itself, inadequate concentrations of it resulting in the induction of the enzyme. The mediator in this regulation, as in hormonal regulation, seems to be cyclic AMP."} {"id": "PMID:173346", "title": "Recent advances in the identification of enzyme abnormalities underlying excessive purine synthesis in man.", "content": "Work is continuing in the attempt to increase knowledge of the regulation of the rate of purine synthesis in man by means of an analysis of biochemical alterations leading to purine overproduction among patients with gout. The authors are now assessing the frequency of kinetic mutations in enzymes whose alterations already have been associated with increased purine synthesis. Efforts in this regard have been rewarded by the identification of a new form of alteration leading to partial deficiency of HGPRT and a kinetic variant of PRPP synthetase with increased affinity for ribose-5-phosphate. In order to identify new forms of enzyme abnormalities associated with excessive purine synthesis, the value of a proposed classification scheme requiring measurement of PRPP and ribose-5-phosphate concentration and generation is being assessed in cultured fibroblasts. It is hoped that the results of these measurements will lead to the identification of additional kinetic variants of presently known enzyme abnormalities and will help to identify new classes of mutants in the regulation of human purine metabolism. The excessive purine synthesis that underlies the hyperuricemia of a substantial number of patients with gouty arthritis reflects alterations in the normal mechanism regulating the rate of purine nucleotide synthesis. The study of such purine \"overproducers\" has provided insight into the nature of this regulatory mechanism and has underscored the diversity of specific genetic and biochemical aberrations affecting it. Despite these advances, however, less than 10% of all patients with gout and excessive purine production can presently be accounted for by known enzyme abnormalities (1). Recognition that current knowledge of the regulation of the rate of purine nucleotide synthesis in man is incomplete has provided the authors impetus leading to the studies described here, which are preceded by a brief review of background.", "contents": "Recent advances in the identification of enzyme abnormalities underlying excessive purine synthesis in man. Work is continuing in the attempt to increase knowledge of the regulation of the rate of purine synthesis in man by means of an analysis of biochemical alterations leading to purine overproduction among patients with gout. The authors are now assessing the frequency of kinetic mutations in enzymes whose alterations already have been associated with increased purine synthesis. Efforts in this regard have been rewarded by the identification of a new form of alteration leading to partial deficiency of HGPRT and a kinetic variant of PRPP synthetase with increased affinity for ribose-5-phosphate. In order to identify new forms of enzyme abnormalities associated with excessive purine synthesis, the value of a proposed classification scheme requiring measurement of PRPP and ribose-5-phosphate concentration and generation is being assessed in cultured fibroblasts. It is hoped that the results of these measurements will lead to the identification of additional kinetic variants of presently known enzyme abnormalities and will help to identify new classes of mutants in the regulation of human purine metabolism. The excessive purine synthesis that underlies the hyperuricemia of a substantial number of patients with gouty arthritis reflects alterations in the normal mechanism regulating the rate of purine nucleotide synthesis. The study of such purine \"overproducers\" has provided insight into the nature of this regulatory mechanism and has underscored the diversity of specific genetic and biochemical aberrations affecting it. Despite these advances, however, less than 10% of all patients with gout and excessive purine production can presently be accounted for by known enzyme abnormalities (1). Recognition that current knowledge of the regulation of the rate of purine nucleotide synthesis in man is incomplete has provided the authors impetus leading to the studies described here, which are preceded by a brief review of background."} {"id": "PMID:173350", "title": "[Studies on the influence of anticoagulants on metastase formation of autochthonic hepatomas in the rat (author's transl)].", "content": "The frequency of metastases of malignant diethylnitrosamine-induced hepatomas and haemangioendotheliomas of the liver of female Sprague-Dawley rats (29%) was not influenced by application of acetyl-salicylic acid or phenprocoumon. Likewise the anticoagulants did not alter tumor yields and induction periods.", "contents": "[Studies on the influence of anticoagulants on metastase formation of autochthonic hepatomas in the rat (author's transl)]. The frequency of metastases of malignant diethylnitrosamine-induced hepatomas and haemangioendotheliomas of the liver of female Sprague-Dawley rats (29%) was not influenced by application of acetyl-salicylic acid or phenprocoumon. Likewise the anticoagulants did not alter tumor yields and induction periods."} {"id": "PMID:173351", "title": "[Experimental results with systematically synthetized substances for antiviral chemotherapy / 4th communication: The role of physical binding in the synthesis of antiviral chemotherapeutics and its influence on potential mutagenic effects (author's transl)].", "content": "13 antiviral substances containing specific hydrogen bridge linkage systems out of the classes of 2-substituted 4-phenylthiazoles, 4-phenylimidazoles and indandiones-(1,3) were tested for their mutagenic potency in the host-mediated assay, in bone marrow of rats, in spermatogonia of mice and in the micronucleus test of rats. Only one substance, N1-methyl-N2-[4-phenylthiazolyl-(2)]-urea, was found to be mutagenic. This fact substantiates the hypothesis that the antiviral effectiveness of the substances is not caused by a chemical change in the coding system but by forming \"physical\" linkages like hydrogen bridge complexes with coding structures. Altogether 159 compounds of very different structures were investigated for their antiviral chemotherapeutic potency in 893 tests in cell cultures and 461 animal tests. It can be stated that compounds with a low molecular weight containing the \"effective structures\" (see article) show a larger yield of antiviral compounds than do substances without these structures (about 50% positive results in cell cultures and 25% in animals 15% and 0%, respectively).", "contents": "[Experimental results with systematically synthetized substances for antiviral chemotherapy / 4th communication: The role of physical binding in the synthesis of antiviral chemotherapeutics and its influence on potential mutagenic effects (author's transl)]. 13 antiviral substances containing specific hydrogen bridge linkage systems out of the classes of 2-substituted 4-phenylthiazoles, 4-phenylimidazoles and indandiones-(1,3) were tested for their mutagenic potency in the host-mediated assay, in bone marrow of rats, in spermatogonia of mice and in the micronucleus test of rats. Only one substance, N1-methyl-N2-[4-phenylthiazolyl-(2)]-urea, was found to be mutagenic. This fact substantiates the hypothesis that the antiviral effectiveness of the substances is not caused by a chemical change in the coding system but by forming \"physical\" linkages like hydrogen bridge complexes with coding structures. Altogether 159 compounds of very different structures were investigated for their antiviral chemotherapeutic potency in 893 tests in cell cultures and 461 animal tests. It can be stated that compounds with a low molecular weight containing the \"effective structures\" (see article) show a larger yield of antiviral compounds than do substances without these structures (about 50% positive results in cell cultures and 25% in animals 15% and 0%, respectively)."} {"id": "PMID:173352", "title": "[Studies on the antigenicity of synthetic ACTH (beta1-24-corticotropin) in normal subjects (author's transl)].", "content": "9 healthy volunteers were subjected to a 3-week treatment with synthetic ACTH. Antibody response against beta1-24-corticotropin (Synacthen) was tested by passive transfer in the Prausnitz-K\u00fcstner reaction, complement fixation, passive hemagglutination and agar-gel diffusion. Failure of the healthy persons to produce reaginic or non-reaginic antibodies is compared titerature.", "contents": "[Studies on the antigenicity of synthetic ACTH (beta1-24-corticotropin) in normal subjects (author's transl)]. 9 healthy volunteers were subjected to a 3-week treatment with synthetic ACTH. Antibody response against beta1-24-corticotropin (Synacthen) was tested by passive transfer in the Prausnitz-K\u00fcstner reaction, complement fixation, passive hemagglutination and agar-gel diffusion. Failure of the healthy persons to produce reaginic or non-reaginic antibodies is compared titerature."} {"id": "PMID:173353", "title": "Metabolism of lipoproteins in nonhuman primates. Reduced secretion of very low density lipoproteins in squirrel monkeys with diet-induced hypercholesterolemia.", "content": "We have studied the effects of diet-induced hypercholesterolemia on the rates of secretion of triglycerides into the plasma of fasted squirrel monkeys. Two groups of monkeys were studied: control animals which were fed a semipurified diet not associated with hyperlipemia (plasma cholesterol 127 +/- 8 mg/100 ml), and animals made hypercholesterolemic (plasma cholesterol 307 +/- 31 mg/100 ml) by being fed a diet containing 25% butter and 0.5% cholesterol. After intravenous infusion of Triton WR 1339 (300 mg/kg body wt), plasma triglycerides increased almost linearly for 9-12 hours. Analysis of individual lipoproteins separated by ultracentrifugation showed that newly secreted triglycerides were present almost exclusively in the very low density lipoprotein fraction. The rates of triglyceride secretion in the hypercholesterolemic group of monkeys (5.15 +/- 0.86 mg/kg/hr) were less than half those of the control animals (10.96 +/- 2.15 mg/kg/hr). We suggest that in monkeys with diet-induced hypercholesterolemia high concentrations of plasma low density lipoproteins may inhibit the synthesis and/or secretion of their parent very low density lipoprotein molecules into the circulation.", "contents": "Metabolism of lipoproteins in nonhuman primates. Reduced secretion of very low density lipoproteins in squirrel monkeys with diet-induced hypercholesterolemia. We have studied the effects of diet-induced hypercholesterolemia on the rates of secretion of triglycerides into the plasma of fasted squirrel monkeys. Two groups of monkeys were studied: control animals which were fed a semipurified diet not associated with hyperlipemia (plasma cholesterol 127 +/- 8 mg/100 ml), and animals made hypercholesterolemic (plasma cholesterol 307 +/- 31 mg/100 ml) by being fed a diet containing 25% butter and 0.5% cholesterol. After intravenous infusion of Triton WR 1339 (300 mg/kg body wt), plasma triglycerides increased almost linearly for 9-12 hours. Analysis of individual lipoproteins separated by ultracentrifugation showed that newly secreted triglycerides were present almost exclusively in the very low density lipoprotein fraction. The rates of triglyceride secretion in the hypercholesterolemic group of monkeys (5.15 +/- 0.86 mg/kg/hr) were less than half those of the control animals (10.96 +/- 2.15 mg/kg/hr). We suggest that in monkeys with diet-induced hypercholesterolemia high concentrations of plasma low density lipoproteins may inhibit the synthesis and/or secretion of their parent very low density lipoprotein molecules into the circulation."} {"id": "PMID:173374", "title": "[Determination of anti-cytomegalovirus antibodies by the immunoperoxidase method: comparison with the methods of complement fixation and immunofluorescence].", "content": "Indirect immunoperoxidase technique (IIP) has been employed for determination of IgG antibody titer to cytomegalovirus (CMV) in sera from 110 blood donors. Titers have been compared with complement fixation (CF) and indirect fluorescent antibody (IFA) technique titers, the latter being applied to determination of all specific antibody classes. Within variability range of the quality of reagents employed in different tests, it seems reasonable to conclude IIP technique is as sensitive as IFA and much more sensitive than CF test. Considering CF test is able to detect only IgG antibody, the advantage of using immunohistochemical techniques is obvious. Moreover IIP does not need fluorescence microscope and results reading is easier and can be delayed. Non-specific staining of Golgi area is shared by both techniques, but endpoint determination has to take into account only the nuclear virus-specific inclusion labelling.", "contents": "[Determination of anti-cytomegalovirus antibodies by the immunoperoxidase method: comparison with the methods of complement fixation and immunofluorescence]. Indirect immunoperoxidase technique (IIP) has been employed for determination of IgG antibody titer to cytomegalovirus (CMV) in sera from 110 blood donors. Titers have been compared with complement fixation (CF) and indirect fluorescent antibody (IFA) technique titers, the latter being applied to determination of all specific antibody classes. Within variability range of the quality of reagents employed in different tests, it seems reasonable to conclude IIP technique is as sensitive as IFA and much more sensitive than CF test. Considering CF test is able to detect only IgG antibody, the advantage of using immunohistochemical techniques is obvious. Moreover IIP does not need fluorescence microscope and results reading is easier and can be delayed. Non-specific staining of Golgi area is shared by both techniques, but endpoint determination has to take into account only the nuclear virus-specific inclusion labelling."} {"id": "PMID:173375", "title": "[The immunoperoxidase technic in the rapid identification of human cytomegalovirus on primary isolation].", "content": "Immunoperoxidase technique has been applied to the rapid identification of human cytomegalovirus (CMV) strains on primary isolation. Negative and positive results have been constantly confirmed by indirect fluorescent antibody technique (IFA) and by electron microscopy. Using either direct or indirect method it was observed that problems of nonspecific staining of uninfected cells were encountered mostly with direct method, probably because of the lower working dilution of the conjugate (1:20) as compared with higher conjugate dilution used for indirect method (1:150). However, nonspecific cytoplasmic stain of Golgi area of infected cells was observed also with indirect method. Pathogenesis of nonspecific labelling of this area is discussed. Application of the immunoperoxidase technique directly into tubes on primary isolation allows to reduce identification time in comparison with IFA technique and is less cumbersome and time-consuming than complement fixation and neutralization tests.", "contents": "[The immunoperoxidase technic in the rapid identification of human cytomegalovirus on primary isolation]. Immunoperoxidase technique has been applied to the rapid identification of human cytomegalovirus (CMV) strains on primary isolation. Negative and positive results have been constantly confirmed by indirect fluorescent antibody technique (IFA) and by electron microscopy. Using either direct or indirect method it was observed that problems of nonspecific staining of uninfected cells were encountered mostly with direct method, probably because of the lower working dilution of the conjugate (1:20) as compared with higher conjugate dilution used for indirect method (1:150). However, nonspecific cytoplasmic stain of Golgi area of infected cells was observed also with indirect method. Pathogenesis of nonspecific labelling of this area is discussed. Application of the immunoperoxidase technique directly into tubes on primary isolation allows to reduce identification time in comparison with IFA technique and is less cumbersome and time-consuming than complement fixation and neutralization tests."} {"id": "PMID:173376", "title": "Intranuclear inclusions in shope fibroma virus infected cells.", "content": "The presence of nuclear inclusions consisting of accumulated filamentous material has been observed in Shope fibroma virus infected cells, analogously to what has been demonstrated in other poxvirus infected cells.", "contents": "Intranuclear inclusions in shope fibroma virus infected cells. The presence of nuclear inclusions consisting of accumulated filamentous material has been observed in Shope fibroma virus infected cells, analogously to what has been demonstrated in other poxvirus infected cells."} {"id": "PMID:173354", "title": "Chylomicron formation and composition in unanaesthetised rabbits.", "content": "Emulsified lipid was infused steadily into the upper small intestine of unanaesthetised rabbits for 6 h and 24 h periods. Lymph was collected from a thoracic duct cannula, the output of infused lipids was measured and the lymph chylomicrons were isolated. Recovery of infused triacylglycerol was 63 +/- 6.4% and recovery of infused radioactive cholesterol was 24 +/- 4.2% during a 24 h period. There was considerable dilution of radioactive exogenous cholesterol with endogenous cholesterol. Provided that absorption was well-established most exogenous lipid was present in the lymph in the form of chylomicrons, and there was a close relationship between lipid content of the lymph and the presence of chylomicrons. During absorption of fats of differing fatty acid composition chylomicrons remained the predominant transport form in the lymph. Chylomicrons obtained during absorption of several fats have been analysed in detail. The protein, phospholipid, free and esterified cholesterol content of these chylomicrons varies within narrow limits. The fatty acid composition of chylomicron triacylglycerols reflects the type of fat in the test meal but the composition of chylomicron phospholipids and cholesteryl esters shows clear discrimination. During absorption of coconut oil there is a strong negative discrimination towards lauric acid both for cholesteryl esters and for phospholipids.", "contents": "Chylomicron formation and composition in unanaesthetised rabbits. Emulsified lipid was infused steadily into the upper small intestine of unanaesthetised rabbits for 6 h and 24 h periods. Lymph was collected from a thoracic duct cannula, the output of infused lipids was measured and the lymph chylomicrons were isolated. Recovery of infused triacylglycerol was 63 +/- 6.4% and recovery of infused radioactive cholesterol was 24 +/- 4.2% during a 24 h period. There was considerable dilution of radioactive exogenous cholesterol with endogenous cholesterol. Provided that absorption was well-established most exogenous lipid was present in the lymph in the form of chylomicrons, and there was a close relationship between lipid content of the lymph and the presence of chylomicrons. During absorption of fats of differing fatty acid composition chylomicrons remained the predominant transport form in the lymph. Chylomicrons obtained during absorption of several fats have been analysed in detail. The protein, phospholipid, free and esterified cholesterol content of these chylomicrons varies within narrow limits. The fatty acid composition of chylomicron triacylglycerols reflects the type of fat in the test meal but the composition of chylomicron phospholipids and cholesteryl esters shows clear discrimination. During absorption of coconut oil there is a strong negative discrimination towards lauric acid both for cholesteryl esters and for phospholipids."} {"id": "PMID:173355", "title": "Properties of two pig low density lipoproteins prepared by zonal ultracentrifugation.", "content": "Pig plasma lipoproteins were separted into four density classes (very low density, two low density and high density lipoproteins, VLDL, LDL1, LDL2 and HDL respectively) from 670 ml plasma by ultracentrifugation in a continuous density gradient using the Spinco Ti15 zonal rotor. LDL1 and LDL2 were partly characterised. LDL1 and LDL2 are beta-migrating lipoproteins of different size and hydrated density; they are similar to human LDL2 and LDL3 respectively. Pig plasma contains about twice as much LDL1 as LDL2. LDL1 migrates at Sf 4.9 (modal value), and has a mean diameter of 217 A and a modal density of 1.035 g/ml (range 1.03-1.04 g/ml). LDL2 migrates at Sf 1.8 and has a mean diameter of 195 A and a density of 1.050 g/ml. Both lipoproteins are precipitated by heparin and Mn++ or by dextran sulphate and Ca++. The apoproteins of LDL1 and LDL2 are both largely insoluble in 8 M urea solution. When dissolved in 1% sodium dodecyl sulphate solution and electrophoresed on polyacrylamide gel at pH 7.0, the apoproteins of LDL1 and LDL2 formed a pattern of multiple bands of high molecular weight similar to that obtained from the apoprotein of human LDL. Both LDL1 and LDL2 share a major antigen with each other and with VLDL; in this respect again they resemble human LDL. The amino acid compositions of LDL1 and LDL2 are very similar. We concluded that the apoprotein moieties of pig plasma LDL1 and LDL2 are probably identical, and similar to apoprotein B in human serum. Zonal ultracentifugation has proved to be a rapid and effective method for isolating large quantities of these two lipoprotein classes for further metabolic studies. This method allows rapid bulk preparation of lipoproteins, and provides a record of their distribution and quantity in a continuous density gradient.", "contents": "Properties of two pig low density lipoproteins prepared by zonal ultracentrifugation. Pig plasma lipoproteins were separted into four density classes (very low density, two low density and high density lipoproteins, VLDL, LDL1, LDL2 and HDL respectively) from 670 ml plasma by ultracentrifugation in a continuous density gradient using the Spinco Ti15 zonal rotor. LDL1 and LDL2 were partly characterised. LDL1 and LDL2 are beta-migrating lipoproteins of different size and hydrated density; they are similar to human LDL2 and LDL3 respectively. Pig plasma contains about twice as much LDL1 as LDL2. LDL1 migrates at Sf 4.9 (modal value), and has a mean diameter of 217 A and a modal density of 1.035 g/ml (range 1.03-1.04 g/ml). LDL2 migrates at Sf 1.8 and has a mean diameter of 195 A and a density of 1.050 g/ml. Both lipoproteins are precipitated by heparin and Mn++ or by dextran sulphate and Ca++. The apoproteins of LDL1 and LDL2 are both largely insoluble in 8 M urea solution. When dissolved in 1% sodium dodecyl sulphate solution and electrophoresed on polyacrylamide gel at pH 7.0, the apoproteins of LDL1 and LDL2 formed a pattern of multiple bands of high molecular weight similar to that obtained from the apoprotein of human LDL. Both LDL1 and LDL2 share a major antigen with each other and with VLDL; in this respect again they resemble human LDL. The amino acid compositions of LDL1 and LDL2 are very similar. We concluded that the apoprotein moieties of pig plasma LDL1 and LDL2 are probably identical, and similar to apoprotein B in human serum. Zonal ultracentifugation has proved to be a rapid and effective method for isolating large quantities of these two lipoprotein classes for further metabolic studies. This method allows rapid bulk preparation of lipoproteins, and provides a record of their distribution and quantity in a continuous density gradient."} {"id": "PMID:173377", "title": "Interaction of Sendai virus with human erythrocytes. III. Further investigation on the effects of pyridine on the virus envelope.", "content": "The ultrastructure of the pyridine-treated Sendai virus has further been investigated by electron microscopy of chemically fixed and negatively stained virions. Marked changes in the ultrastructural appearance of the viral envelope have been detected. The extent of these changes depends on pyridine dose and ranges from minor extraction of the outer track components to multiple breaks and disintegration of the whole envelope. At 16% pyridine a fragmentation of viral nucleocapsid has also been noted. Both the nature of these changes and the fact that even fully burst viral particles can eventually retain regularly-arranged spikes, strongly suggest that pyridine primarily affects the organization of the double-track viral membrane, probably by sequential extraction of lipids and protein components. The results are discussed in the light of the selective property of pyridine in discriminating among the biological activities of the Sendai virus and give additional support to the idea that phospholipids and a glycoprotein spike play cooperative roles in the hemolytic activity of the virus.", "contents": "Interaction of Sendai virus with human erythrocytes. III. Further investigation on the effects of pyridine on the virus envelope. The ultrastructure of the pyridine-treated Sendai virus has further been investigated by electron microscopy of chemically fixed and negatively stained virions. Marked changes in the ultrastructural appearance of the viral envelope have been detected. The extent of these changes depends on pyridine dose and ranges from minor extraction of the outer track components to multiple breaks and disintegration of the whole envelope. At 16% pyridine a fragmentation of viral nucleocapsid has also been noted. Both the nature of these changes and the fact that even fully burst viral particles can eventually retain regularly-arranged spikes, strongly suggest that pyridine primarily affects the organization of the double-track viral membrane, probably by sequential extraction of lipids and protein components. The results are discussed in the light of the selective property of pyridine in discriminating among the biological activities of the Sendai virus and give additional support to the idea that phospholipids and a glycoprotein spike play cooperative roles in the hemolytic activity of the virus."} {"id": "PMID:173356", "title": "The plasma and tissue turnover and distribution of two radio-iodine-labelled pig plasma low density lipoproteins.", "content": "Two classes of pig plasma low density lipoprotein (LDL1 and LDL2) with different densities and molecular sizes were isolated by zonal ultracentrifugation and were further purified by flotation. The peptide component was iodinated with 125I, and the labelled lipoprotein was injected intravenously. 125I-LDL1 turnover studies were performed on 22 3-4 month old female Large White pigs, and 125I-LDL2 turnover studies on 4 similar pigs. A biological screening experiment confirmed that the shape of the plasma activity curve was not a function of protein denaturation. The pattern of radioactivity decline in plasma was not affected by the degree of LDL iodination. 125I-LDL1 turnover: The curve of plasma radioactivity plotted against time over the first 5 days after injection could be resolved into two exponentials. The plasma biological half-life (T 1/2) was calculated from the slower exponential predominant from the second day. The mean T 1/2 over 2-5 days was 22.9 hr (range 17.2-28.5 hr). Multicompartmental analysis of the plasma decay curve using an open mammillary model gave a mean fractional catabolic rate per day for LDL1 of 1.4 (range 0.9-1.9). The mean T 1/2 was 0.26-0.31 times and the fractional catabolic rate 3.0-3.9 times those values found in two studies on adult humans. The tissue distribution of 125I was analysed in a series of 20 animals killed from 1.0 to 33.8 days after 125I-LDL1 injection. Most tissue 125I (86-89%) was protein bound. An appropriate correction was made to the 125I counts for retained plasma in liver and spleen (using 131I-albumin); retained plasma in other tissues was negligible. Highest 125I tissue levels were found in the liver, supporting other evidence that the liver may be the major site of LDL1 catabolism. After 2.06 and 4.06 days the livers in two animals contained 1.6% and 0.7% respectively of the total injected 125I, equal to 33% and 54% of the total plasma 125I at those times. The skin contained about one-third to one-ninth the 125I in the liver at various times. Distribution in other organs was quantitatively minimal. Higher levels of radioactivity were found in the intima and inner media of the aorta than in the outer media. These results suggest that plasma LDL in the pig diffuses through the endothelial surface into the arterial wall. These findings are confirmed by autoradiography. 125I-LDL2 turnover: Parallel studies of plasma 125I-LDL2 turnover and tissue distribution were performed. The plasma biological decay curve was multi-exponential, suggesting that LDL2 metabolism is complex, and possibly more rapid than that of LDL1 (LDL2 is smaller and denser than LDL1). The tissue distribution of 125I-LDL2 in these pigs was very similar to that of 125I-LDL1. As LDL1 and LDL2 differ in the amount of lipid they contain, they may have different roles to play in lipid transport, and there may be interconversion of one into the other at different sites. This hypothesis remains conjectural.", "contents": "The plasma and tissue turnover and distribution of two radio-iodine-labelled pig plasma low density lipoproteins. Two classes of pig plasma low density lipoprotein (LDL1 and LDL2) with different densities and molecular sizes were isolated by zonal ultracentrifugation and were further purified by flotation. The peptide component was iodinated with 125I, and the labelled lipoprotein was injected intravenously. 125I-LDL1 turnover studies were performed on 22 3-4 month old female Large White pigs, and 125I-LDL2 turnover studies on 4 similar pigs. A biological screening experiment confirmed that the shape of the plasma activity curve was not a function of protein denaturation. The pattern of radioactivity decline in plasma was not affected by the degree of LDL iodination. 125I-LDL1 turnover: The curve of plasma radioactivity plotted against time over the first 5 days after injection could be resolved into two exponentials. The plasma biological half-life (T 1/2) was calculated from the slower exponential predominant from the second day. The mean T 1/2 over 2-5 days was 22.9 hr (range 17.2-28.5 hr). Multicompartmental analysis of the plasma decay curve using an open mammillary model gave a mean fractional catabolic rate per day for LDL1 of 1.4 (range 0.9-1.9). The mean T 1/2 was 0.26-0.31 times and the fractional catabolic rate 3.0-3.9 times those values found in two studies on adult humans. The tissue distribution of 125I was analysed in a series of 20 animals killed from 1.0 to 33.8 days after 125I-LDL1 injection. Most tissue 125I (86-89%) was protein bound. An appropriate correction was made to the 125I counts for retained plasma in liver and spleen (using 131I-albumin); retained plasma in other tissues was negligible. Highest 125I tissue levels were found in the liver, supporting other evidence that the liver may be the major site of LDL1 catabolism. After 2.06 and 4.06 days the livers in two animals contained 1.6% and 0.7% respectively of the total injected 125I, equal to 33% and 54% of the total plasma 125I at those times. The skin contained about one-third to one-ninth the 125I in the liver at various times. Distribution in other organs was quantitatively minimal. Higher levels of radioactivity were found in the intima and inner media of the aorta than in the outer media. These results suggest that plasma LDL in the pig diffuses through the endothelial surface into the arterial wall. These findings are confirmed by autoradiography. 125I-LDL2 turnover: Parallel studies of plasma 125I-LDL2 turnover and tissue distribution were performed. The plasma biological decay curve was multi-exponential, suggesting that LDL2 metabolism is complex, and possibly more rapid than that of LDL1 (LDL2 is smaller and denser than LDL1). The tissue distribution of 125I-LDL2 in these pigs was very similar to that of 125I-LDL1. As LDL1 and LDL2 differ in the amount of lipid they contain, they may have different roles to play in lipid transport, and there may be interconversion of one into the other at different sites. This hypothesis remains conjectural."} {"id": "PMID:173378", "title": "[Effect of cyclic nucleotides on the transformation and proliferation of lymphocytes].", "content": "When the studies on the immunologic system have met with the \"second messenger\" hypothesis of the cyclic nucleotides, new ideas have arisen about mechanisms regulating the immunologic reactions. Several works sustain a specific action of cyclic AMP and cyclic GMP to modulate the immunologic system, but the more subtle actions must be discovered. A hypothesis which attributes the control-task of the cellular functions to the c-AMP/c-GMP relation is presented.", "contents": "[Effect of cyclic nucleotides on the transformation and proliferation of lymphocytes]. When the studies on the immunologic system have met with the \"second messenger\" hypothesis of the cyclic nucleotides, new ideas have arisen about mechanisms regulating the immunologic reactions. Several works sustain a specific action of cyclic AMP and cyclic GMP to modulate the immunologic system, but the more subtle actions must be discovered. A hypothesis which attributes the control-task of the cellular functions to the c-AMP/c-GMP relation is presented."} {"id": "PMID:173379", "title": "Characterization of the T antigen induced by SV40.", "content": "3 or 4 antigenic SV40 specific components were established in hamster tumors induced by SV40-transformed cells, using linear sucrose gradient centrifugation and Sephadex G-200 column chromatography. The lightest component, approximate molecular weight 21,000, did not inhibit the nuclear staining of SV40-transformed cells in the fluorescent antibody inhibition test.", "contents": "Characterization of the T antigen induced by SV40. 3 or 4 antigenic SV40 specific components were established in hamster tumors induced by SV40-transformed cells, using linear sucrose gradient centrifugation and Sephadex G-200 column chromatography. The lightest component, approximate molecular weight 21,000, did not inhibit the nuclear staining of SV40-transformed cells in the fluorescent antibody inhibition test."} {"id": "PMID:173380", "title": "Renal subcellular fractions producing angionecrosis and increased vascular permeability.", "content": "In order to define the subcellular localization and characters of substances in the rat kidney which increase vascular permeability and produce angionecrosis, the following investigations have been undertaken: (1) subcellular fractionation by use of differential centrifugation and osmotic shock treatment with enzyme profile determination; (2) chromatographic separation of lysosomal contents with concanavalin A affinity column. Lysomal contents contained substances that induced an increase of vascular permeability of the rabbit skin and angionecrosis in the pancreas of the bilaterally nephrectomized rats and the spontaneously hypertensive rats. Lysosomal contents treated at 60 degrees for 30 min showed no renin activity and yet produced angionecrosis. Non-affinity fraction from concanavalin A column chromatography showed no renin activity but produced angionecrosis and an increase of vascular permeability of rabbit skin.", "contents": "Renal subcellular fractions producing angionecrosis and increased vascular permeability. In order to define the subcellular localization and characters of substances in the rat kidney which increase vascular permeability and produce angionecrosis, the following investigations have been undertaken: (1) subcellular fractionation by use of differential centrifugation and osmotic shock treatment with enzyme profile determination; (2) chromatographic separation of lysosomal contents with concanavalin A affinity column. Lysomal contents contained substances that induced an increase of vascular permeability of the rabbit skin and angionecrosis in the pancreas of the bilaterally nephrectomized rats and the spontaneously hypertensive rats. Lysosomal contents treated at 60 degrees for 30 min showed no renin activity and yet produced angionecrosis. Non-affinity fraction from concanavalin A column chromatography showed no renin activity but produced angionecrosis and an increase of vascular permeability of rabbit skin."} {"id": "PMID:173381", "title": "The occurrence of vacuolated neurons in the brains of hamsters affected with subacute sclerosing encephalitis following measles or Langat virus infection.", "content": "Hamsters infected by the intranasal route with either hamster adapted Langat virus passaged at least 10 times in hamsters and the HNT strain of measles virus passaged 149 times in hamsters, developed subacute sclerotic lesions in the pyriform cortex, and beginning from 2 months after infection, were accompanied by neuronal vacuolation with ballooning of the cytoplasm, especially in parts of the brain in close proximity of the sclerotic lesions. The vacuolated neurons resembled those seen in scrapie, especially of sheep and goats, suggesting a similarity between the effects of slow and subacute viral infections.", "contents": "The occurrence of vacuolated neurons in the brains of hamsters affected with subacute sclerosing encephalitis following measles or Langat virus infection. Hamsters infected by the intranasal route with either hamster adapted Langat virus passaged at least 10 times in hamsters and the HNT strain of measles virus passaged 149 times in hamsters, developed subacute sclerotic lesions in the pyriform cortex, and beginning from 2 months after infection, were accompanied by neuronal vacuolation with ballooning of the cytoplasm, especially in parts of the brain in close proximity of the sclerotic lesions. The vacuolated neurons resembled those seen in scrapie, especially of sheep and goats, suggesting a similarity between the effects of slow and subacute viral infections."} {"id": "PMID:173382", "title": "Diverse mechanisms of hepatocellular injuries due to chemicals: evidence in rats administered carbon tetrachloride or dimethylnitrosamine.", "content": "Differences in acute hepatotoxicity of carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN) have been tested in normal foetal, newborn and adult rats, foetal, newborn and adult rats pretreated with phenobarbitone and partially hepatectomized adult rats. While CCl4 is non-toxic to the foetal and newborn liver, DMN induces identical necrosis at all ages. Prior dosing with phenobarbitone augments CCl4 toxicity only in the adult and the newborn but the foetus continues to be resistant. Such pretreatment, on the other hand, significantly reduces the effects of DMN on liver in all animals. Partial hepatectomy makes the liver less susceptible to CCl4 and more so to DMN. Such diversities of hepatic response to the two toxins can be accounted for by the levels of the respective toxifying enzymes in the liver cell in different situations.", "contents": "Diverse mechanisms of hepatocellular injuries due to chemicals: evidence in rats administered carbon tetrachloride or dimethylnitrosamine. Differences in acute hepatotoxicity of carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN) have been tested in normal foetal, newborn and adult rats, foetal, newborn and adult rats pretreated with phenobarbitone and partially hepatectomized adult rats. While CCl4 is non-toxic to the foetal and newborn liver, DMN induces identical necrosis at all ages. Prior dosing with phenobarbitone augments CCl4 toxicity only in the adult and the newborn but the foetus continues to be resistant. Such pretreatment, on the other hand, significantly reduces the effects of DMN on liver in all animals. Partial hepatectomy makes the liver less susceptible to CCl4 and more so to DMN. Such diversities of hepatic response to the two toxins can be accounted for by the levels of the respective toxifying enzymes in the liver cell in different situations."} {"id": "PMID:173383", "title": "Tubuloreticular structures in human lymphoid cell lines. A cell biological study.", "content": "Human lymphoid cell lines were studied as an experimental model for the spontaneous or induced occurrence of tuburloreticular structures (TRS). It was possible to induce TRS after culturing the EB-3 cell line with 20 mug/ml bromodeoxyuridine (BrUdR) during 96 h. Starvation, culturing at lower temperature (32 degrees) or inhibition of DNA synthesis did not give rise to the production of TRS. The response to BrUdR could be blocked with 60 mug/ml thymidine but not with 60 mug/ml deoxycytidine. The addition of 5 mug/ml cytarabine or the removal of BrUdR at different times resulted in inhibition of TRS induction, indicating that BrUdR had to be incorporated into DNA during at least 48 h. After incorporation, neither the presence of BrUdR nor DNA synthesis was necessary for the production of TRS. These experiments and the finding that in the cell line IHTC-33, which does not produce Epstein-Barr virus associated antigens, TRS were spontaneously present, exclude a correlation between TRS and these antigens. However, the induction of TRS by BrUdR may be related to the activation of another (latent) virus.", "contents": "Tubuloreticular structures in human lymphoid cell lines. A cell biological study. Human lymphoid cell lines were studied as an experimental model for the spontaneous or induced occurrence of tuburloreticular structures (TRS). It was possible to induce TRS after culturing the EB-3 cell line with 20 mug/ml bromodeoxyuridine (BrUdR) during 96 h. Starvation, culturing at lower temperature (32 degrees) or inhibition of DNA synthesis did not give rise to the production of TRS. The response to BrUdR could be blocked with 60 mug/ml thymidine but not with 60 mug/ml deoxycytidine. The addition of 5 mug/ml cytarabine or the removal of BrUdR at different times resulted in inhibition of TRS induction, indicating that BrUdR had to be incorporated into DNA during at least 48 h. After incorporation, neither the presence of BrUdR nor DNA synthesis was necessary for the production of TRS. These experiments and the finding that in the cell line IHTC-33, which does not produce Epstein-Barr virus associated antigens, TRS were spontaneously present, exclude a correlation between TRS and these antigens. However, the induction of TRS by BrUdR may be related to the activation of another (latent) virus."} {"id": "PMID:173384", "title": "Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1.", "content": "Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.", "contents": "Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution."} {"id": "PMID:173385", "title": "Ultrastructural localization and differentiation of membrane-bound ATP utilizing enzymes including adenyl cyclase in normal and psoriatic epidermis.", "content": "The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells.", "contents": "Ultrastructural localization and differentiation of membrane-bound ATP utilizing enzymes including adenyl cyclase in normal and psoriatic epidermis. The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells."} {"id": "PMID:173386", "title": "Cellular immunity and circulating antibody to herpes simplex virus in subjects with recurrent herpex simplex lesions and controls as measured by the mixed leukocyte migration inhibition test and complement fixation.", "content": "Cellular immune responses and circulating antibody levels to herpes simplex virus were examined in patients with recurrent herpes simplex (HSV) infections and controls. Mixed leukocyte migration inhibition by herpes simplex antigen was less in affected patients than in controls but serum antibody levels were higher. There was no significant difference in leukocyte migration between patients with active or recent lesions and other herpes subjects, and the response in the mixed leukocyte migration test to phytohaemagglutinin (PHA) was similar in patients and controls. The data presented suggest that a localized defect in cell mediated immunity to herpes simplex virus may exist and be responsible for recurrent herpes simplex infections.", "contents": "Cellular immunity and circulating antibody to herpes simplex virus in subjects with recurrent herpex simplex lesions and controls as measured by the mixed leukocyte migration inhibition test and complement fixation. Cellular immune responses and circulating antibody levels to herpes simplex virus were examined in patients with recurrent herpes simplex (HSV) infections and controls. Mixed leukocyte migration inhibition by herpes simplex antigen was less in affected patients than in controls but serum antibody levels were higher. There was no significant difference in leukocyte migration between patients with active or recent lesions and other herpes subjects, and the response in the mixed leukocyte migration test to phytohaemagglutinin (PHA) was similar in patients and controls. The data presented suggest that a localized defect in cell mediated immunity to herpes simplex virus may exist and be responsible for recurrent herpes simplex infections."} {"id": "PMID:173388", "title": "An epidemic of picornavirus and adenovirus conjunctivitis.", "content": "A pandemic of acute haemorrhagic conjunctivitis occurred in south-east Asia during 1970 and 1971, and became epidemic in Lucknow in May 1971. From the conjunctival swabs adenovirus-like agents were isolated in monkey kidney tissue culture; one was typed as adenovirus 2. In paired sera rising antibody titres were found against an adeno-like agent isolated and the picornavirus (EC2/71) isolated in Singapore. The epidemics in south-east Asia were caused by a picornavirus while in Lucknow both adenovirus and picornavirus appeared to be implicated.", "contents": "An epidemic of picornavirus and adenovirus conjunctivitis. A pandemic of acute haemorrhagic conjunctivitis occurred in south-east Asia during 1970 and 1971, and became epidemic in Lucknow in May 1971. From the conjunctival swabs adenovirus-like agents were isolated in monkey kidney tissue culture; one was typed as adenovirus 2. In paired sera rising antibody titres were found against an adeno-like agent isolated and the picornavirus (EC2/71) isolated in Singapore. The epidemics in south-east Asia were caused by a picornavirus while in Lucknow both adenovirus and picornavirus appeared to be implicated."} {"id": "PMID:173389", "title": "Studies on NO2-Tyr82and NH2-Tyr82 derivatives of adrenodoxin. Effects of chemical modification on electron transferring activity.", "content": "Bovine apoadrenodoxin was treated with tetranitromethane to introduce a nitro group into the tyrosyl residue at position 82 of this protein. The degrees of nitration under the best conditions were estimated to be 90% and nearly 100% on the basis of amino acid analysis and the spectrophotometric method, respectively. An amino derivative was prepared by reducing the nitro group with sodium dithionite. The apoadrenodoxin derivatives could be reconstituted to have an iron-sulfur chromophore similar to the native adrenodoxin which contains a 1:1 molar ratio of labile sulfur to iron content and displays absorption peaks at 414 and 450 nm. The enzymatic acitivies of these reconstituted nitro and amino derivatives toward cytochrome c reduction in the presence of adrenodoxin reductase and NADPH were 19 and 7% of native adrenodoxin, respectively. We studied the kinetics of the direct reduction of the reconstituted amino derivative in the presence of NADPH and adrenodoxin reductase under anaerobic conditons. The initial rate of reduction for the amino derivative was 7% of the native adrenodoxin, which is in good agreement with its activity toward cytochrome c reduction. From these results, it is concluded that by modifying the tyrosyl residue at position 82 of the adrenodoxin polypeptide, the electron-transferring activity of the molecule is largely diminished.", "contents": "Studies on NO2-Tyr82and NH2-Tyr82 derivatives of adrenodoxin. Effects of chemical modification on electron transferring activity. Bovine apoadrenodoxin was treated with tetranitromethane to introduce a nitro group into the tyrosyl residue at position 82 of this protein. The degrees of nitration under the best conditions were estimated to be 90% and nearly 100% on the basis of amino acid analysis and the spectrophotometric method, respectively. An amino derivative was prepared by reducing the nitro group with sodium dithionite. The apoadrenodoxin derivatives could be reconstituted to have an iron-sulfur chromophore similar to the native adrenodoxin which contains a 1:1 molar ratio of labile sulfur to iron content and displays absorption peaks at 414 and 450 nm. The enzymatic acitivies of these reconstituted nitro and amino derivatives toward cytochrome c reduction in the presence of adrenodoxin reductase and NADPH were 19 and 7% of native adrenodoxin, respectively. We studied the kinetics of the direct reduction of the reconstituted amino derivative in the presence of NADPH and adrenodoxin reductase under anaerobic conditons. The initial rate of reduction for the amino derivative was 7% of the native adrenodoxin, which is in good agreement with its activity toward cytochrome c reduction. From these results, it is concluded that by modifying the tyrosyl residue at position 82 of the adrenodoxin polypeptide, the electron-transferring activity of the molecule is largely diminished."} {"id": "PMID:173390", "title": "Stimulation of cholesterol ester exchange by lipoprotein-free rabbit plasma.", "content": "A fraction in normal and hypercholesterolemic rabbit plasma of density greater than 1.25 stimulates the exchange of cholesterol esters between very low density and low density lipoproteins from hypercholesterolemic rabbit plasma. The exchange does not result from lecithin:cholesterol acyltransferase activity. The active factor appears to be a high molecular weight globulin with an isolelectric point of 5.2.", "contents": "Stimulation of cholesterol ester exchange by lipoprotein-free rabbit plasma. A fraction in normal and hypercholesterolemic rabbit plasma of density greater than 1.25 stimulates the exchange of cholesterol esters between very low density and low density lipoproteins from hypercholesterolemic rabbit plasma. The exchange does not result from lecithin:cholesterol acyltransferase activity. The active factor appears to be a high molecular weight globulin with an isolelectric point of 5.2."} {"id": "PMID:173391", "title": "Conformational changes of glyceraldehyde-3-phosphate dehydrogenase induced by the binding of NAD. A unified model for positive and negative cooperativity.", "content": "The fluorescence of the natural coenzyme, NADH, is used to monitor the environment of the nicotinamide moiety at the active centre of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Changes of the fluorescence quantum yield and polarization of a small amount of NADH, totally bound by an excess of enzyme, show that at half-saturation of the oligomer with NAD a conformational change is induced which affects the active centre regions of the remaining subunits. This conformational transition is not effected by adenosine diphosphoribose, suggesting that the binding of the nicotinamide moiety of NAD to two subunits is essential for the change of tertiary structure of the remaining subunits that causes the observed changes of the fluorescence properties of the ADH \"tracer probe\". It is suggested that this conformational transition of the oligomer is responsible for the major decrease of affinity for NAD which occurs at half-saturation, and possibly for the activation by NAD+ of the reductive dephosphorylation reaction catalysed by the enzyme. It is also suggested, by analogy with haemoglobin, that the molecular basis of the negative cooperativity may be the creation of additional intersubunit bonds during the binding of the first two NAD molecules to the tetramer, and a change from a \"relaxed\" quaternary structure to a \"tense\" structure at half-saturation.", "contents": "Conformational changes of glyceraldehyde-3-phosphate dehydrogenase induced by the binding of NAD. A unified model for positive and negative cooperativity. The fluorescence of the natural coenzyme, NADH, is used to monitor the environment of the nicotinamide moiety at the active centre of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Changes of the fluorescence quantum yield and polarization of a small amount of NADH, totally bound by an excess of enzyme, show that at half-saturation of the oligomer with NAD a conformational change is induced which affects the active centre regions of the remaining subunits. This conformational transition is not effected by adenosine diphosphoribose, suggesting that the binding of the nicotinamide moiety of NAD to two subunits is essential for the change of tertiary structure of the remaining subunits that causes the observed changes of the fluorescence properties of the ADH \"tracer probe\". It is suggested that this conformational transition of the oligomer is responsible for the major decrease of affinity for NAD which occurs at half-saturation, and possibly for the activation by NAD+ of the reductive dephosphorylation reaction catalysed by the enzyme. It is also suggested, by analogy with haemoglobin, that the molecular basis of the negative cooperativity may be the creation of additional intersubunit bonds during the binding of the first two NAD molecules to the tetramer, and a change from a \"relaxed\" quaternary structure to a \"tense\" structure at half-saturation."} {"id": "PMID:173392", "title": "Further studies on the activation of microsomal (Na+ + k+)-atpase by a leukocytic product.", "content": "Previous studies showed that microsomal (Na+ + K+)ATPase (ATP phosphohydrolase, EC 3.6.1.3) is activated by a proteinaeous material released by polymorphonuclear leukocytes. Investigations on the mode of action of the activator have been conducted by the siolation of 32P-labeled phosphoenzyme intermediates formed in the reaction of ATP and (Na+ + K)-ATPase, which has been postulated to occur through the formation and hydrolysis of acyl phosphate intermediates. The activator caused a concentration-dependent decrease in the recovery of phosphoenzyme intermediates that was not quantitatively altered by the Na+ or K+ concentration of the reaction mixture of by the presence of 1 mM oubain. A decline in phosphoenzyme intermediate recovery was promoted by the addition of the activator to preformed phosphoenzyme intermediates but not by activator that had been pretreated with protease or phenol. In addition, the activator caused a concentration-dependent stimulation of the p-nitrophenyl phosphatase and acetyl phosphatase activities of microsomal (Na+ + K+)-ATPase. It was proposed that the activator stimulates the dephosphorylation step of the (Na+ + K+)-ATPase reaction sequence.", "contents": "Further studies on the activation of microsomal (Na+ + k+)-atpase by a leukocytic product. Previous studies showed that microsomal (Na+ + K+)ATPase (ATP phosphohydrolase, EC 3.6.1.3) is activated by a proteinaeous material released by polymorphonuclear leukocytes. Investigations on the mode of action of the activator have been conducted by the siolation of 32P-labeled phosphoenzyme intermediates formed in the reaction of ATP and (Na+ + K)-ATPase, which has been postulated to occur through the formation and hydrolysis of acyl phosphate intermediates. The activator caused a concentration-dependent decrease in the recovery of phosphoenzyme intermediates that was not quantitatively altered by the Na+ or K+ concentration of the reaction mixture of by the presence of 1 mM oubain. A decline in phosphoenzyme intermediate recovery was promoted by the addition of the activator to preformed phosphoenzyme intermediates but not by activator that had been pretreated with protease or phenol. In addition, the activator caused a concentration-dependent stimulation of the p-nitrophenyl phosphatase and acetyl phosphatase activities of microsomal (Na+ + K+)-ATPase. It was proposed that the activator stimulates the dephosphorylation step of the (Na+ + K+)-ATPase reaction sequence."} {"id": "PMID:173393", "title": "Inhibition of peptide chain initiation in lysates from ATP-depleted cells.I. Stages in the evolution of the lesion and its reversal by thiol compounds, cyclic AMP or purine derivatives and phosphorylated sugars.", "content": "Anaerobic incubation of rabbit reticulocytes at 37 degrees C in Krebs-Ringer solution supplemented with hemin but devoid of glucose resulted at the end of 1-2h in a drastic decline of their ATP content and an attendant arrest of protein synthesis. Subsequent provision of glucose and reoxygenation of the cells was followed by a rapid replenishment of the ATP pool, while resumption of protein synthesis was markedly delayed. This lag period could be considerably reduced by addition of 5-10 mM adenine or 2,6-diaminopurine to the incubation medium. Lysates prepared from ATP-depleted cells exhibited disaggregation of the polysomes and an inhibition of the nedogenously coded protein synthesis, when tested in a cell-free system supplied with an adequate ATP generator. Both alterations increased in severity with the progressive decay of the intracellular ATP pool. The early phase of partial inhibition following a 40-70% decrease of the cellular ATP level was fully reversible by fortifying the cell-free preparation with dithiothreitol or a suitable NADPH-generating system. Aternative, the inhibition could be also overcome by millimolar amounts of adenine, 2,6-diaminopurine and a variety of other purine derivatives or cyclic AMP. The effect of these compounds was unrelated to the endogenous cyclic AMP pool. Joint addition of both dithiothreitol and cyclic AMP or adenine was necessary for relieving the initiation block in lysates derived from cells depleted of 80-90% of their ATP content. On further aggravating the conditions of energy starvation, an additional requirement for phosphorylated sugars, e.g. glucose 6-phosphate or fructose 1,6-diphosphate, became apparent. ATP depletion brought about by exposing the cells to Antimycin A or 2,4-dinitrophenol resulted in a lesion which was indistinguishable from that induced by anaerobic incubation. On the other hand, energy deprivation in cell-free lysates from untreated reticulocytes, preincubated in the absence of an ATP-generating system failed to duplicate the deleterious effect of intracellular ATP depletion. Some aspects bearing on the biochemical mechanism of the lesion and its reversal are discussed in the light of the available data.", "contents": "Inhibition of peptide chain initiation in lysates from ATP-depleted cells.I. Stages in the evolution of the lesion and its reversal by thiol compounds, cyclic AMP or purine derivatives and phosphorylated sugars. Anaerobic incubation of rabbit reticulocytes at 37 degrees C in Krebs-Ringer solution supplemented with hemin but devoid of glucose resulted at the end of 1-2h in a drastic decline of their ATP content and an attendant arrest of protein synthesis. Subsequent provision of glucose and reoxygenation of the cells was followed by a rapid replenishment of the ATP pool, while resumption of protein synthesis was markedly delayed. This lag period could be considerably reduced by addition of 5-10 mM adenine or 2,6-diaminopurine to the incubation medium. Lysates prepared from ATP-depleted cells exhibited disaggregation of the polysomes and an inhibition of the nedogenously coded protein synthesis, when tested in a cell-free system supplied with an adequate ATP generator. Both alterations increased in severity with the progressive decay of the intracellular ATP pool. The early phase of partial inhibition following a 40-70% decrease of the cellular ATP level was fully reversible by fortifying the cell-free preparation with dithiothreitol or a suitable NADPH-generating system. Aternative, the inhibition could be also overcome by millimolar amounts of adenine, 2,6-diaminopurine and a variety of other purine derivatives or cyclic AMP. The effect of these compounds was unrelated to the endogenous cyclic AMP pool. Joint addition of both dithiothreitol and cyclic AMP or adenine was necessary for relieving the initiation block in lysates derived from cells depleted of 80-90% of their ATP content. On further aggravating the conditions of energy starvation, an additional requirement for phosphorylated sugars, e.g. glucose 6-phosphate or fructose 1,6-diphosphate, became apparent. ATP depletion brought about by exposing the cells to Antimycin A or 2,4-dinitrophenol resulted in a lesion which was indistinguishable from that induced by anaerobic incubation. On the other hand, energy deprivation in cell-free lysates from untreated reticulocytes, preincubated in the absence of an ATP-generating system failed to duplicate the deleterious effect of intracellular ATP depletion. Some aspects bearing on the biochemical mechanism of the lesion and its reversal are discussed in the light of the available data."} {"id": "PMID:173394", "title": "Inhibition of peptide chain initiation in lysates from ATP-depleted cells. II. Studies on the mechanism of the lesion and its relation to similar alterations caused by oxidized glutathione and hemin deprivation.", "content": "The impairment of peptide chain initiation in lysates from ATP-depleted rabbit reticulocytes is accompanied by a loss of their ability to form the 40 S methionyl-tRNAfMet complex with a resultant failure to promote the AUG codon-dependent combination of the complex with the 60 S ribosomal subunit. These partial initiation reactions, as well as the overall protein-synthetic activity of the defective lysates could be restored by addition of a 0.5 M KC1 ribosomal extract or normal postribosomal supernatant or a 40-70% (NH4)2-SO4 fraction derived from it. Alternatively, reactivation of the impaired lysates could be achieved by supplementation with millimolar amounts of cyclic AMP or certain purine derivatives. The same subcellular fractions, as well as cyclic AMP or purine derivatives were also capable of overcoming the inhibition caused by incubating reticulocyte lysates in the presence of oxidized glutathione or in the absence of hemin. Severe intracellular ATP deprivation resulted in accumulation of a soluble translational inhibitor in the postribosomal fraction, thus resembling the parallel phenomenon described in hemin-deprived lysates. The striking similarities between the three kinds of inhibition studied by us point to an identical site of the underlying biochemical lesion, despite the different mechanisms mediating their induction.", "contents": "Inhibition of peptide chain initiation in lysates from ATP-depleted cells. II. Studies on the mechanism of the lesion and its relation to similar alterations caused by oxidized glutathione and hemin deprivation. The impairment of peptide chain initiation in lysates from ATP-depleted rabbit reticulocytes is accompanied by a loss of their ability to form the 40 S methionyl-tRNAfMet complex with a resultant failure to promote the AUG codon-dependent combination of the complex with the 60 S ribosomal subunit. These partial initiation reactions, as well as the overall protein-synthetic activity of the defective lysates could be restored by addition of a 0.5 M KC1 ribosomal extract or normal postribosomal supernatant or a 40-70% (NH4)2-SO4 fraction derived from it. Alternatively, reactivation of the impaired lysates could be achieved by supplementation with millimolar amounts of cyclic AMP or certain purine derivatives. The same subcellular fractions, as well as cyclic AMP or purine derivatives were also capable of overcoming the inhibition caused by incubating reticulocyte lysates in the presence of oxidized glutathione or in the absence of hemin. Severe intracellular ATP deprivation resulted in accumulation of a soluble translational inhibitor in the postribosomal fraction, thus resembling the parallel phenomenon described in hemin-deprived lysates. The striking similarities between the three kinds of inhibition studied by us point to an identical site of the underlying biochemical lesion, despite the different mechanisms mediating their induction."} {"id": "PMID:173396", "title": "Protein synthesis in homologous and heterologous cell-free systems from chick embryo connective tissues.", "content": "Two homologous systems for cell-free protein synthesis from chick embryo connective tissues are described. Both the skin polysomes and the wing-leg polysomes are active in collagen synthesis, but they have different requirements for optimum protein synthesis. Protein synthesis was not dependent on tissue-specific factors, since heterologous preparations of supernatant enzymes or initiation factors were able to stimulate maximum protein synthesis with each fraction of polysomes.", "contents": "Protein synthesis in homologous and heterologous cell-free systems from chick embryo connective tissues. Two homologous systems for cell-free protein synthesis from chick embryo connective tissues are described. Both the skin polysomes and the wing-leg polysomes are active in collagen synthesis, but they have different requirements for optimum protein synthesis. Protein synthesis was not dependent on tissue-specific factors, since heterologous preparations of supernatant enzymes or initiation factors were able to stimulate maximum protein synthesis with each fraction of polysomes."} {"id": "PMID:173397", "title": "Calcium ion uptake in isolated pancreas cells induced by secretagogues.", "content": "1. Secretagogues of pancreatic enzyme secretion: pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, caerulein and the Ca2+ ionophore A 23187 stimulate 45Ca uptake into isolated rat pancreatic cells, whereas adrenaline, isoproterenol, secretin, dibutyrylic cyclic adenosine 3',5'-monophosphate and dibutyrylic cyclic guanosine 3',5'-monophosphate have no effect on 45Ca uptake. 2. A graphical analysis of the Ca2+ uptake curves reveals at least two phases: a fast phase, probably due to binding of Ca2+ to the membrane and a slow phase representing Ca2+ transport into cells. Both phases are stimulated by pancreozymin and carbamylcholine. 3. The 45Ca-exchangeable pool size is increased by both carbamylcholine and pancreozymin, whereas a significant increase of total content of cell calcium was too small to be detected. 4. Atropine blocks the stimulatory effect of carbamylcholine completely but not that of pancreozymin. The Ca2+ antagonist D600 blocks the stimulatory effects of both carbamylcholine and pancreozymin only partially. 5. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca2+ transfer into the cell most probably through an increase of the cell membrane permeability for Ca2+.", "contents": "Calcium ion uptake in isolated pancreas cells induced by secretagogues. 1. Secretagogues of pancreatic enzyme secretion: pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, caerulein and the Ca2+ ionophore A 23187 stimulate 45Ca uptake into isolated rat pancreatic cells, whereas adrenaline, isoproterenol, secretin, dibutyrylic cyclic adenosine 3',5'-monophosphate and dibutyrylic cyclic guanosine 3',5'-monophosphate have no effect on 45Ca uptake. 2. A graphical analysis of the Ca2+ uptake curves reveals at least two phases: a fast phase, probably due to binding of Ca2+ to the membrane and a slow phase representing Ca2+ transport into cells. Both phases are stimulated by pancreozymin and carbamylcholine. 3. The 45Ca-exchangeable pool size is increased by both carbamylcholine and pancreozymin, whereas a significant increase of total content of cell calcium was too small to be detected. 4. Atropine blocks the stimulatory effect of carbamylcholine completely but not that of pancreozymin. The Ca2+ antagonist D600 blocks the stimulatory effects of both carbamylcholine and pancreozymin only partially. 5. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca2+ transfer into the cell most probably through an increase of the cell membrane permeability for Ca2+."} {"id": "PMID:173398", "title": "Involvement of sulfhydryl groups in the action of the insulin and radiation on thymocyte Na+-dependent amino acid transport.", "content": "1,p-Chloromercuribenzene sulfonate concentrations less than 10(-5) M stimulate the uptake by thymocytes of 2-aminoisobutyrate, a non-metabolized amino acid. At concentrations greater than 10(-5) M of this reagent, transport is impaired and cell viability is effected. In contrast, 5,5'-dithiobis-(2-nitrobenzoate) between 10(-4) and 10(-6) M produces only stimulation of 2-aminoisobutyrate uptake after treating for 10 min. 2. Treatment of thymocytes with 10(-4)M 5,5'-dithiobis-(2-nitrobenzoate) reveals at least three categories of reactive SH groups. Titration of the most rapidly reacting category, 4 - 10(7)-7 - 10(7)/cell, activates 2-aminoisobutyrate transport to the same extent as does p-chloromercuribenzene sulfonate. Cells treated with 10(-6) M insulin showed a 30-50% reduction in the number of sulfhydryl groups that could be titrated with 5,5'-dithiobis-(2-nitrobenzoate). In thymocytes treated with 10(-6) M p-chloro(203Hg)mercuribenzene sulfonate, addition of 10(-6) or 10(-9) M insulin before treatment with the sulhydryl reagent again reduces the number of titrable SH groups by 20%. 3. Insulin (10(-10)-10(-6) M) also stimulates 2-aminoisobutyrate uptake, but the effects of insulin and SH blocker are not additive. 4. Insulin, but not p-chloromercuribenzene sulfonate, prevents the impairment of 2-aminoisobutyrate transport caused by gamma-irradiation. Treatment of cells with p-chloromercuribenzene sulfonate prior to irradiation increases the radiation impairment of 2-aminoisobutyrate transport. 5. gamma-irradiation reduces the number of 5,5'-dithiobis-(2-nitrobenzoate) reactive sulfhydryl residues by 37%. 6. A model for the action of insulin and irradiation on 2-aminoisobutyrate transport is presented.", "contents": "Involvement of sulfhydryl groups in the action of the insulin and radiation on thymocyte Na+-dependent amino acid transport. 1,p-Chloromercuribenzene sulfonate concentrations less than 10(-5) M stimulate the uptake by thymocytes of 2-aminoisobutyrate, a non-metabolized amino acid. At concentrations greater than 10(-5) M of this reagent, transport is impaired and cell viability is effected. In contrast, 5,5'-dithiobis-(2-nitrobenzoate) between 10(-4) and 10(-6) M produces only stimulation of 2-aminoisobutyrate uptake after treating for 10 min. 2. Treatment of thymocytes with 10(-4)M 5,5'-dithiobis-(2-nitrobenzoate) reveals at least three categories of reactive SH groups. Titration of the most rapidly reacting category, 4 - 10(7)-7 - 10(7)/cell, activates 2-aminoisobutyrate transport to the same extent as does p-chloromercuribenzene sulfonate. Cells treated with 10(-6) M insulin showed a 30-50% reduction in the number of sulfhydryl groups that could be titrated with 5,5'-dithiobis-(2-nitrobenzoate). In thymocytes treated with 10(-6) M p-chloro(203Hg)mercuribenzene sulfonate, addition of 10(-6) or 10(-9) M insulin before treatment with the sulhydryl reagent again reduces the number of titrable SH groups by 20%. 3. Insulin (10(-10)-10(-6) M) also stimulates 2-aminoisobutyrate uptake, but the effects of insulin and SH blocker are not additive. 4. Insulin, but not p-chloromercuribenzene sulfonate, prevents the impairment of 2-aminoisobutyrate transport caused by gamma-irradiation. Treatment of cells with p-chloromercuribenzene sulfonate prior to irradiation increases the radiation impairment of 2-aminoisobutyrate transport. 5. gamma-irradiation reduces the number of 5,5'-dithiobis-(2-nitrobenzoate) reactive sulfhydryl residues by 37%. 6. A model for the action of insulin and irradiation on 2-aminoisobutyrate transport is presented."} {"id": "PMID:173399", "title": "[Structural transitions in DNA, isolated from normal and neoplastic cells].", "content": "A decrease of temperature transition in spin-labeled DNA isolated from leucose cells compared with normal cells is found. It is shown by kinetic formaldehyde method that it may be the result of many defects in the secondary structure of macromolecule in DNA1. The spin label method is shown to be used for the analysis of DNA macromolecule damaged with small irradiation doses. Various radiosensitivity of DNA isolated from the blood of normal and leucose cells is observed.", "contents": "[Structural transitions in DNA, isolated from normal and neoplastic cells]. A decrease of temperature transition in spin-labeled DNA isolated from leucose cells compared with normal cells is found. It is shown by kinetic formaldehyde method that it may be the result of many defects in the secondary structure of macromolecule in DNA1. The spin label method is shown to be used for the analysis of DNA macromolecule damaged with small irradiation doses. Various radiosensitivity of DNA isolated from the blood of normal and leucose cells is observed."} {"id": "PMID:173400", "title": "[EPR- and IR-spectroscopic study of the processes of carbonization of amino acid crystals].", "content": "Initial stages of \"low temperature\" carbonization in crystal amino acids have been studied by ESR- and IR-spectroscopy. It was revealed that block polycondensation of amino acids with the formation of polypeptide chains took place. In the air oxygen also surface carbonization of crystals took place; it became stronger with the occurrence of radiation defects.", "contents": "[EPR- and IR-spectroscopic study of the processes of carbonization of amino acid crystals]. Initial stages of \"low temperature\" carbonization in crystal amino acids have been studied by ESR- and IR-spectroscopy. It was revealed that block polycondensation of amino acids with the formation of polypeptide chains took place. In the air oxygen also surface carbonization of crystals took place; it became stronger with the occurrence of radiation defects."} {"id": "PMID:173401", "title": "[Electron paramagnetic resonance study of photosensitized transport and localization of electrons in enzyme-substrate complexes. Lysozyme and its inhibitor].", "content": "Photosensitized electron transfer are studied in three systems: lysozyme, its inhibitors (oligosaccharides) and their enzyme-inhibitor complexes. Electron donors were either tryptophane amino acid residues of lysozyme or tryptophane. It is shown that N-acetyl group of inhibitor molecules is a single electron--acceptor group in the inhibitor molecule as well as in the lysozyme-inhibitor complex. It is stated that the localization of unpaired electrons in the mixtures of lysozyme modification products and substrate--inhibitors depends on the state of enzyme molecule.", "contents": "[Electron paramagnetic resonance study of photosensitized transport and localization of electrons in enzyme-substrate complexes. Lysozyme and its inhibitor]. Photosensitized electron transfer are studied in three systems: lysozyme, its inhibitors (oligosaccharides) and their enzyme-inhibitor complexes. Electron donors were either tryptophane amino acid residues of lysozyme or tryptophane. It is shown that N-acetyl group of inhibitor molecules is a single electron--acceptor group in the inhibitor molecule as well as in the lysozyme-inhibitor complex. It is stated that the localization of unpaired electrons in the mixtures of lysozyme modification products and substrate--inhibitors depends on the state of enzyme molecule."} {"id": "PMID:173402", "title": "[Mechanism of the formation of paramagnetic centers in proteins exposed to UV-radiation].", "content": "It is shown that the process of formation of paramagnetic centres in UV-irradiated at 77degreesK protein solutions in a biquantum one. The protein molecule in triplet state is an intermediate product.", "contents": "[Mechanism of the formation of paramagnetic centers in proteins exposed to UV-radiation]. It is shown that the process of formation of paramagnetic centres in UV-irradiated at 77degreesK protein solutions in a biquantum one. The protein molecule in triplet state is an intermediate product."} {"id": "PMID:173403", "title": "[Accumulation of paramagnetic centers in protein solutions exposed to UV-radiation].", "content": "It is shown that concentration of paramagnetic centres (PC) in UV-irradiated protein solutions at 77degreesK approximates the limiting value. The limiting number of PC (n) per one molecule is in direct proportion to that of aromatic amino acid residues in it n(sigma)=2+0,1 sigma. The formation of PC slopps because all the energy absorbed by aromatic amino acid residues is transfered to the radicals formed.", "contents": "[Accumulation of paramagnetic centers in protein solutions exposed to UV-radiation]. It is shown that concentration of paramagnetic centres (PC) in UV-irradiated protein solutions at 77degreesK approximates the limiting value. The limiting number of PC (n) per one molecule is in direct proportion to that of aromatic amino acid residues in it n(sigma)=2+0,1 sigma. The formation of PC slopps because all the energy absorbed by aromatic amino acid residues is transfered to the radicals formed."} {"id": "PMID:173404", "title": "[Spin label study of microviscosity and structural transitions in cell membrane lipids and proteins. I. Heat-induced structural changes in cell nuclei of mouse organs in normal conditions].", "content": "With the help of weakly bound spin probes the effect of temperature on structural transitions of protein and lipid components in the nuclei membranes of different organs of intact mice has been studied. Microviscosity of lipids in the membrane is found to differ sharply from proteins. Found by both probes breaks on Arrhenius curve of the correlation time dependence on reverse temperature within the temperature range of 25degreesC--27degreesC and 40degreesC-43degreesC seem to be connected with structural reconstructions of the whole membrane. The results obtained according to the behaviour of probes are identical for the nuclei of different organs.", "contents": "[Spin label study of microviscosity and structural transitions in cell membrane lipids and proteins. I. Heat-induced structural changes in cell nuclei of mouse organs in normal conditions]. With the help of weakly bound spin probes the effect of temperature on structural transitions of protein and lipid components in the nuclei membranes of different organs of intact mice has been studied. Microviscosity of lipids in the membrane is found to differ sharply from proteins. Found by both probes breaks on Arrhenius curve of the correlation time dependence on reverse temperature within the temperature range of 25degreesC--27degreesC and 40degreesC-43degreesC seem to be connected with structural reconstructions of the whole membrane. The results obtained according to the behaviour of probes are identical for the nuclei of different organs."} {"id": "PMID:173405", "title": "[Properties of the thalamocortical nonspecific system].", "content": "A study has been carried out on how parameters of stimulation of thalamo-cortical non-specific system in the rabbit brain influence the amplitude and temporal characteristics of a recruiting response.", "contents": "[Properties of the thalamocortical nonspecific system]. A study has been carried out on how parameters of stimulation of thalamo-cortical non-specific system in the rabbit brain influence the amplitude and temporal characteristics of a recruiting response."} {"id": "PMID:173407", "title": "[Rate of interaction of ferricytochrome c with negatively charged liposomes from natural lecithin: effect of the physicochemical state of the membrane hydrophobic layer].", "content": "The absorption velocity of ferricytochrome c on the surface of liposomes from egg lecithin containing 10% of lauric acid was studied. Liposomes were prepared from lecithin of three fractions which differed by the composition of fatty acids, unsaturation and the lipid interaction decreased at the temperature below T phi pi for lecithin fractions containing larger quantity of saturated fatty acids. An opposite tendency was observed for the temperature above T phi pi. In the phase transition region of lecithin of refractory fraction the local maximum of protein-lipid interaction was observed. Judging by the character of the changes of the values of energy activation, small additions of cholesterol in the membrane loosen the bilayer at the temperature below T phi pi and condense it at above T phi pi. The data obtained are discussed in terms of the effect of the state of molecule hydrophobic part on the velocity of protein-lipid interaction.", "contents": "[Rate of interaction of ferricytochrome c with negatively charged liposomes from natural lecithin: effect of the physicochemical state of the membrane hydrophobic layer]. The absorption velocity of ferricytochrome c on the surface of liposomes from egg lecithin containing 10% of lauric acid was studied. Liposomes were prepared from lecithin of three fractions which differed by the composition of fatty acids, unsaturation and the lipid interaction decreased at the temperature below T phi pi for lecithin fractions containing larger quantity of saturated fatty acids. An opposite tendency was observed for the temperature above T phi pi. In the phase transition region of lecithin of refractory fraction the local maximum of protein-lipid interaction was observed. Judging by the character of the changes of the values of energy activation, small additions of cholesterol in the membrane loosen the bilayer at the temperature below T phi pi and condense it at above T phi pi. The data obtained are discussed in terms of the effect of the state of molecule hydrophobic part on the velocity of protein-lipid interaction."} {"id": "PMID:173409", "title": "[EPR study of electron transport in higher plant photosynthetic systems. II. Effect of temperature on the kinetics of photoinduced oxidation-reduction transformations of P700].", "content": "A sharp fall of ESR signal I is observed at temperature decrease while switching on light of 600 nm on the background of light of 707 nm; kinetics of the initiation of the signal under the illumination of light of 707 nm gets more complicated; the induction phase induced by previous illumination with the light of 600 nm increases.", "contents": "[EPR study of electron transport in higher plant photosynthetic systems. II. Effect of temperature on the kinetics of photoinduced oxidation-reduction transformations of P700]. A sharp fall of ESR signal I is observed at temperature decrease while switching on light of 600 nm on the background of light of 707 nm; kinetics of the initiation of the signal under the illumination of light of 707 nm gets more complicated; the induction phase induced by previous illumination with the light of 600 nm increases."} {"id": "PMID:173410", "title": "[EPR spectra of animal tissues in vitro].", "content": "The ESR spectra of animal tissues have been recorded at 13-43 degrees K. The reduction of the ESR signal intensities of the Fe-S proteins have been found in starving mice which is due to the substrate diminishing in these animal tissues.", "contents": "[EPR spectra of animal tissues in vitro]. The ESR spectra of animal tissues have been recorded at 13-43 degrees K. The reduction of the ESR signal intensities of the Fe-S proteins have been found in starving mice which is due to the substrate diminishing in these animal tissues."} {"id": "PMID:173408", "title": "[EPR study of electron transport in higher plant photosynthetic systems. I. Effect of illumination prehistory on the kinetics of photoinduced oxidation-reduction transformations of P700].", "content": "After the adaptation of leaves to darkness (2--4 min) the kinetics of the initiation of ESR I signal aquires a multiphase character: after an initial leap the stage of slower growth sets in. The \"memory\" of the system about the effect of light of 600 nm, which was realized as a delay of the growth of the ESR I signal under the effect of light of 707 nm, was preserved in the darkness for several minutes. If the light of 600 nm is switched on at the background of the light of 707 nm not earlier than 2-4 min after its switching off in the preceding cycle, unmonotonous transitional process with an overleap is observed.", "contents": "[EPR study of electron transport in higher plant photosynthetic systems. I. Effect of illumination prehistory on the kinetics of photoinduced oxidation-reduction transformations of P700]. After the adaptation of leaves to darkness (2--4 min) the kinetics of the initiation of ESR I signal aquires a multiphase character: after an initial leap the stage of slower growth sets in. The \"memory\" of the system about the effect of light of 600 nm, which was realized as a delay of the growth of the ESR I signal under the effect of light of 707 nm, was preserved in the darkness for several minutes. If the light of 600 nm is switched on at the background of the light of 707 nm not earlier than 2-4 min after its switching off in the preceding cycle, unmonotonous transitional process with an overleap is observed."} {"id": "PMID:173411", "title": "[Incorporation of low molecular SH-containing compounds in nitrosyl complexes of nonheme iron in cell-free and cell preparations].", "content": "It has been shown that the endogenic low molecular SH-containing compounds in non-cellular liver and yeast preparates include in nitrosyl non-haem iron complexes at basic pH and in result of addition of iron salts into these preparates. The content of nitrosyl non-haem complexes with SH-containing low molecular compounds is not more than 0,5-1% of the quantity of identical non-haem iron complexes with RS-groups of proteins. The low content of these complexes appear to be due to as the low content of low molecular compounds with ionized RS-groups as the competitive action and RS-groups of proteins for iron and NO.", "contents": "[Incorporation of low molecular SH-containing compounds in nitrosyl complexes of nonheme iron in cell-free and cell preparations]. It has been shown that the endogenic low molecular SH-containing compounds in non-cellular liver and yeast preparates include in nitrosyl non-haem iron complexes at basic pH and in result of addition of iron salts into these preparates. The content of nitrosyl non-haem complexes with SH-containing low molecular compounds is not more than 0,5-1% of the quantity of identical non-haem iron complexes with RS-groups of proteins. The low content of these complexes appear to be due to as the low content of low molecular compounds with ionized RS-groups as the competitive action and RS-groups of proteins for iron and NO."} {"id": "PMID:173415", "title": "Purification and some properties of rabbit skeletal muscle fructose 6-phosphate kinase inhibitor.", "content": "The loss of activity of rabbit skeletal muscle FPK on storage and its restoration by ATP, AMP and cyclic AMP has prompted us to look for an inhibitory unit of the enzyme. We have purified this inhibitory factor from the crude muscle extract and isolated from crystalline FPK; both proteins have the same Mw of about 68,000 (SDS). Carboxymethylation revealed species of lower molecular weight. It is suggested that two different kinds of FPK exist, one composed only of \"active\" subunits and another composed only of \"inactive\" (inhibitor) subunits. States of intermediate activity exist, created by dissociation, reassociation and exchange of subunits, because the inhibitor and FPK share several subunits. A model is proposed where one or several inhibitors of molecular mass 68,000 replace the corresponding number of active subunits of 93,000 daltons, the structure of the native molecule remaining tetrameric. It is shown that cyclic AMP exerts its activation function on FPK only in the presence of the inhibitory protein, probably by displacing the exchange of the subunit in favor of the active tetrameric species of 360,000. Ammonium chloride plays probably an opposite role in this exchange. The inhibitor coverts the Michaelian behavior with respect to F-6-P into a cooperative response (sigmoidal shape of the curve) characterized by a Hill coefficient of 2. The Michaelian response with respect to ATP is preserved, the corresponding constant being only slightly affected. In the presence of subsaturating concentration of inhibitor, mixed species are detected. As a first approximation one can propose that a reversible equilibrium exists between free and complex FPK subunits. The dissociation constant of this equilibrium being equal to 4 X 10(-8) M in moles of FPK protomers.", "contents": "Purification and some properties of rabbit skeletal muscle fructose 6-phosphate kinase inhibitor. The loss of activity of rabbit skeletal muscle FPK on storage and its restoration by ATP, AMP and cyclic AMP has prompted us to look for an inhibitory unit of the enzyme. We have purified this inhibitory factor from the crude muscle extract and isolated from crystalline FPK; both proteins have the same Mw of about 68,000 (SDS). Carboxymethylation revealed species of lower molecular weight. It is suggested that two different kinds of FPK exist, one composed only of \"active\" subunits and another composed only of \"inactive\" (inhibitor) subunits. States of intermediate activity exist, created by dissociation, reassociation and exchange of subunits, because the inhibitor and FPK share several subunits. A model is proposed where one or several inhibitors of molecular mass 68,000 replace the corresponding number of active subunits of 93,000 daltons, the structure of the native molecule remaining tetrameric. It is shown that cyclic AMP exerts its activation function on FPK only in the presence of the inhibitory protein, probably by displacing the exchange of the subunit in favor of the active tetrameric species of 360,000. Ammonium chloride plays probably an opposite role in this exchange. The inhibitor coverts the Michaelian behavior with respect to F-6-P into a cooperative response (sigmoidal shape of the curve) characterized by a Hill coefficient of 2. The Michaelian response with respect to ATP is preserved, the corresponding constant being only slightly affected. In the presence of subsaturating concentration of inhibitor, mixed species are detected. As a first approximation one can propose that a reversible equilibrium exists between free and complex FPK subunits. The dissociation constant of this equilibrium being equal to 4 X 10(-8) M in moles of FPK protomers."} {"id": "PMID:173416", "title": "Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents.", "content": "1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions.", "contents": "Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents. 1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions."} {"id": "PMID:173413", "title": "[Spin-labeled nucleosides, nucleoside-5'-mono-, di-, and triphosphates].", "content": "A general method of synthesis of spin-labeled nucleosides, nucleoside-5'-mono-, di- and triphosphates is developed. It is based on the acyllation of ribose OH-group with N-(2,2,5,5-tetramethyl-3-carbonylpyrollin-1-oxyl)-imidasole. Their ESR and UV-spectra are studied. While studying the products of interaction between nucleoside mono-, di- and triphosphates and N-(2,2,5,5-tetramethyl-3-carbonylpyrrolin-1-oxyl)-imidasole along with the formation of monoradicals due to the acyllation of 2'(3')-OH-groups of ribose in the case of AMP, GMP and GDP acyllation by the phosphate group with the formation of biradicals has been also observed.", "contents": "[Spin-labeled nucleosides, nucleoside-5'-mono-, di-, and triphosphates]. A general method of synthesis of spin-labeled nucleosides, nucleoside-5'-mono-, di- and triphosphates is developed. It is based on the acyllation of ribose OH-group with N-(2,2,5,5-tetramethyl-3-carbonylpyrollin-1-oxyl)-imidasole. Their ESR and UV-spectra are studied. While studying the products of interaction between nucleoside mono-, di- and triphosphates and N-(2,2,5,5-tetramethyl-3-carbonylpyrrolin-1-oxyl)-imidasole along with the formation of monoradicals due to the acyllation of 2'(3')-OH-groups of ribose in the case of AMP, GMP and GDP acyllation by the phosphate group with the formation of biradicals has been also observed."} {"id": "PMID:173417", "title": "Effects of catecholamines on rat myocardial metabolism. II. Influence of catecholamines on 32p-incorporation into rat myocardial adenylic nucleotides and their turn-over.", "content": "1. The influence of catecholamines (adrenaline and noradrenaline) on 32Pi incorporation into intracellular phosphate and adenylic nucleotides has been studied on rat myocardium slices; consequently, the turn-over of nucleotides could be determined and compared under the influence of these two hormones. 2. In order to specify the site of action of these catecholamines, several inhibitors and activators of energetic metabolism were included in the incubation medium: 3'5'-AMP, caffein, ouabain, oligomycin, rotenone + antimycin. 3. Both catecholamines favour Pi exchanges between intra and extracellular spaces; ATP turn-over is greatly increased, while ADP turn-over is slightly decreased, and 32P-incorporation into ADP is increased. 4. 3'5'-AMP and caffein are without effect on Pi penetration; however, caffein increases catecholamine effects on this penetration. ATP turn-over is slightly increased by 3'5'-AMP or caffein. 5. Ouabain decreases ATP turn-over but does not prevent the adrenaline induced acceleration. Inhibitors of oxidative phosphorylation and electron transport decrease ATP-turn-over severely; this inhibition is not released by catecholamines. 6. It is concluded that the catecholamine effects observed are dependent on the oxidative phosphorylations process. The increase of Pi exchange by catecholamines may be related to the increase of extracellular space and cation translocations we observed with the hormones.", "contents": "Effects of catecholamines on rat myocardial metabolism. II. Influence of catecholamines on 32p-incorporation into rat myocardial adenylic nucleotides and their turn-over. 1. The influence of catecholamines (adrenaline and noradrenaline) on 32Pi incorporation into intracellular phosphate and adenylic nucleotides has been studied on rat myocardium slices; consequently, the turn-over of nucleotides could be determined and compared under the influence of these two hormones. 2. In order to specify the site of action of these catecholamines, several inhibitors and activators of energetic metabolism were included in the incubation medium: 3'5'-AMP, caffein, ouabain, oligomycin, rotenone + antimycin. 3. Both catecholamines favour Pi exchanges between intra and extracellular spaces; ATP turn-over is greatly increased, while ADP turn-over is slightly decreased, and 32P-incorporation into ADP is increased. 4. 3'5'-AMP and caffein are without effect on Pi penetration; however, caffein increases catecholamine effects on this penetration. ATP turn-over is slightly increased by 3'5'-AMP or caffein. 5. Ouabain decreases ATP turn-over but does not prevent the adrenaline induced acceleration. Inhibitors of oxidative phosphorylation and electron transport decrease ATP-turn-over severely; this inhibition is not released by catecholamines. 6. It is concluded that the catecholamine effects observed are dependent on the oxidative phosphorylations process. The increase of Pi exchange by catecholamines may be related to the increase of extracellular space and cation translocations we observed with the hormones."} {"id": "PMID:173414", "title": "[Need to measure the viscosity of solutions of globular proteins when studying their rotational mobility by the spin probe method].", "content": "It is shown that for correct determination of correlation time of protein rotation, at least for high concentration, it is necessary to measure the viscosities of investigated solvents, whereas for definition by method of extrapolation values Azz the viscosity of water solution of sucrose may be taken as the viscosity of investigated solutions.", "contents": "[Need to measure the viscosity of solutions of globular proteins when studying their rotational mobility by the spin probe method]. It is shown that for correct determination of correlation time of protein rotation, at least for high concentration, it is necessary to measure the viscosities of investigated solvents, whereas for definition by method of extrapolation values Azz the viscosity of water solution of sucrose may be taken as the viscosity of investigated solutions."} {"id": "PMID:173419", "title": "[Effect of endogenous lipid peroxides on respiration in rat liver mitochondria].", "content": "Effect of Fe2+- and ascorbate-induced lipid peroxidation on mitochondrial respiration in 3 and 4 states (according to Chance) is studied. Peroxidation was shown to result in an increase of the oxygen uptake rate in 4th state, and in the KCl-containing medium (but not in sucrose medium) it caused a decrease of the oxygen uptake rate in the phosphorylating state, which partially reversed when cytochrom c was added. These effects were observed only after the development of peroxidation (after \"slow\" flash of chemiluminescence), and the value of and effect correlated with the content of peroxidation products unsaturated fatty acids. No considerable differences in the damaging effect of peroxidation were observed under incubation of mitochondria in KCl, NaCl and choline containing media.", "contents": "[Effect of endogenous lipid peroxides on respiration in rat liver mitochondria]. Effect of Fe2+- and ascorbate-induced lipid peroxidation on mitochondrial respiration in 3 and 4 states (according to Chance) is studied. Peroxidation was shown to result in an increase of the oxygen uptake rate in 4th state, and in the KCl-containing medium (but not in sucrose medium) it caused a decrease of the oxygen uptake rate in the phosphorylating state, which partially reversed when cytochrom c was added. These effects were observed only after the development of peroxidation (after \"slow\" flash of chemiluminescence), and the value of and effect correlated with the content of peroxidation products unsaturated fatty acids. No considerable differences in the damaging effect of peroxidation were observed under incubation of mitochondria in KCl, NaCl and choline containing media."} {"id": "PMID:173420", "title": "[Kinetic studies of the formation of abortive ternary complex lactate dehydrogenase (isoenzyme h4)-NAD-pyruvate].", "content": "The rate constants and equilibrium constants for four stages of process of the abortive ternary complex lactate dehydrogenase (porcine isoenzyme H4)-NAD-pyruvate formation are determined. These stages are 1) the enolization of pyruvate, 2) the formation of binary complex enzyme-NAD, 3) the formation of \"intermediate\" ternary complex enzyme-NAD-enol and 4) the transformation of \"intermediate\" complex into \"final\" ternary one, accumulation of the latter being followed by spectrophotometric and fluorometric methods. The constants obtained were compared with the corresponding ones for porcine isoenzyme M4 determined in earlier work. It was shown that the greater stability of ternary complex and the greater initial rate of ternary complex formation in the case of H4 is due to greater affinity of isoenzyme H4 with respect to NAD, greater magnitude of reaction rate constant for transformation of \"intermediate\" ternary complex into \"final\" one and lesser magnitude of reaction rate constant for the reverse transition.", "contents": "[Kinetic studies of the formation of abortive ternary complex lactate dehydrogenase (isoenzyme h4)-NAD-pyruvate]. The rate constants and equilibrium constants for four stages of process of the abortive ternary complex lactate dehydrogenase (porcine isoenzyme H4)-NAD-pyruvate formation are determined. These stages are 1) the enolization of pyruvate, 2) the formation of binary complex enzyme-NAD, 3) the formation of \"intermediate\" ternary complex enzyme-NAD-enol and 4) the transformation of \"intermediate\" complex into \"final\" ternary one, accumulation of the latter being followed by spectrophotometric and fluorometric methods. The constants obtained were compared with the corresponding ones for porcine isoenzyme M4 determined in earlier work. It was shown that the greater stability of ternary complex and the greater initial rate of ternary complex formation in the case of H4 is due to greater affinity of isoenzyme H4 with respect to NAD, greater magnitude of reaction rate constant for transformation of \"intermediate\" ternary complex into \"final\" one and lesser magnitude of reaction rate constant for the reverse transition."} {"id": "PMID:173421", "title": "[Protamine as a specific inhibitor of electron transport between cytochromes c and a on the outer surface of the mitochondrial membrane].", "content": "The basic protein protamine is found to be a potent inhibitor of mitochondrial cytochrome c oxidase, while the oxidase activity of the \"inside out\" submitochondrial particles is only slightly affected by this polycation. The site of inhibition of mitochondrial respiration by protamine is localized between cytochromes c and a, protamine combining with cytochrome oxidase competitively to cytochrome, c, Ki=2,5 x 10(-6) M. The data obtained suggest that it is the outer side of the mitochondrial membrane where oxidation of cytochrome c by cytochrome a occurs.", "contents": "[Protamine as a specific inhibitor of electron transport between cytochromes c and a on the outer surface of the mitochondrial membrane]. The basic protein protamine is found to be a potent inhibitor of mitochondrial cytochrome c oxidase, while the oxidase activity of the \"inside out\" submitochondrial particles is only slightly affected by this polycation. The site of inhibition of mitochondrial respiration by protamine is localized between cytochromes c and a, protamine combining with cytochrome oxidase competitively to cytochrome, c, Ki=2,5 x 10(-6) M. The data obtained suggest that it is the outer side of the mitochondrial membrane where oxidation of cytochrome c by cytochrome a occurs."} {"id": "PMID:173422", "title": "[On different forms of glyceraldehyde-3-phosphate dehydrogenase].", "content": "Evidence is presented for the structural differences between rat and rabbit skeletal muscle glyceraldehyde-3-phosphate dehydrogenases. Glyceral-dehyde-3-phosphate dehydrogenases isolated from frozen and fresh rat skeletal muscle were found to have different temperature stability and chromatographic behavior on CM-cellulose. Different nucleotide content of the preparations (NAD on one hand, and products of its degradation - ADP-ribose, AMP and adenosine, on the other) is shown to account for the observed effects.", "contents": "[On different forms of glyceraldehyde-3-phosphate dehydrogenase]. Evidence is presented for the structural differences between rat and rabbit skeletal muscle glyceraldehyde-3-phosphate dehydrogenases. Glyceral-dehyde-3-phosphate dehydrogenases isolated from frozen and fresh rat skeletal muscle were found to have different temperature stability and chromatographic behavior on CM-cellulose. Different nucleotide content of the preparations (NAD on one hand, and products of its degradation - ADP-ribose, AMP and adenosine, on the other) is shown to account for the observed effects."} {"id": "PMID:173426", "title": "[Formation of polysomes in virus-specific RNA in the transcriptive complex of Sendai virus infected cells].", "content": "Transcriptive complex in the cytoplasm of Sendai virus infected cells included parental RNA in the form of ribonucleoprotein, nascent RNA and polysomes. Its buoyant density in CsC1 was 1.45 g/ml. The complex dissociated three hours after the infection, and nascent RNA was fully separated from the parental RNP. The template for polysomes within the complex was identified under conditions when the complex was dissociated in cycloheximide-treated cells. Polysomes were revealed in the association with nascent RNA. They sedimented in preribosmal region of sucrose gradient, and had a buoyant density in CsC1 of 1.49 g/ml. Mild treatment with ribonuclease split the polysomes into monoribosomes.", "contents": "[Formation of polysomes in virus-specific RNA in the transcriptive complex of Sendai virus infected cells]. Transcriptive complex in the cytoplasm of Sendai virus infected cells included parental RNA in the form of ribonucleoprotein, nascent RNA and polysomes. Its buoyant density in CsC1 was 1.45 g/ml. The complex dissociated three hours after the infection, and nascent RNA was fully separated from the parental RNP. The template for polysomes within the complex was identified under conditions when the complex was dissociated in cycloheximide-treated cells. Polysomes were revealed in the association with nascent RNA. They sedimented in preribosmal region of sucrose gradient, and had a buoyant density in CsC1 of 1.49 g/ml. Mild treatment with ribonuclease split the polysomes into monoribosomes."} {"id": "PMID:173423", "title": "[Biosynthesis of collagen and non-collagen proteins on free and bound polysomes from chick embryo].", "content": "Synthesys of collagen and non-collagen proteins was investigated in a cell-free system in the presence of free and bound polysomes isolated from chick embryos. Of total radioactive proteins synthesized on bound and free polysomes the amount of peptides digested by bacterial collagenase comprised 25-40% and 5-7% respectively. These data showed that collagen was predominantly synthesized by bound polysomes. Free polysomes were found to be much more active than bound ones in non-collagen protein synthesis. When bound polysomes detached from membranes by detergent treatment were incubated in a cell-free system, a release of non-collagen proteins into the incubation medium increased sharply, but the release of collagen peptides was as negligible as in the case of untreated polysomes. Kinetic studies of collagen synthetizing activity of polysomes bound to or detached from membranes suggested the role of endoplasmic membranes in stabilizing collagenous polysomes.", "contents": "[Biosynthesis of collagen and non-collagen proteins on free and bound polysomes from chick embryo]. Synthesys of collagen and non-collagen proteins was investigated in a cell-free system in the presence of free and bound polysomes isolated from chick embryos. Of total radioactive proteins synthesized on bound and free polysomes the amount of peptides digested by bacterial collagenase comprised 25-40% and 5-7% respectively. These data showed that collagen was predominantly synthesized by bound polysomes. Free polysomes were found to be much more active than bound ones in non-collagen protein synthesis. When bound polysomes detached from membranes by detergent treatment were incubated in a cell-free system, a release of non-collagen proteins into the incubation medium increased sharply, but the release of collagen peptides was as negligible as in the case of untreated polysomes. Kinetic studies of collagen synthetizing activity of polysomes bound to or detached from membranes suggested the role of endoplasmic membranes in stabilizing collagenous polysomes."} {"id": "PMID:173425", "title": "[Isolation of highly purified ribonuclease from cobra (Naja oxiana) venom].", "content": "Dialysis, gel-chromatography on Sephadex G-75 (superfine) and chromatography on sulphoethylcellulose give high yield (68 per cent) of 162-fold purified ribonuclease from cobra venom. In ion-exchange chromatography, ribonuclease is eluted in two fractions. The fraction with the highest specific activity has a molecular weight of 15900 and is homogeneous in 15 per cent polyacrilamide gel electrophoresis at pH 8.9. Electrophoresis at pH 4.3 reveals a minor fast component of this fraction which also exhibits a ribonuclease activity. Sulphoethylcellulose chromatography fairly separates cobra venom phosphodiesterase and 5'-nucleotidase eluted as a single fraction in gel chromatography.", "contents": "[Isolation of highly purified ribonuclease from cobra (Naja oxiana) venom]. Dialysis, gel-chromatography on Sephadex G-75 (superfine) and chromatography on sulphoethylcellulose give high yield (68 per cent) of 162-fold purified ribonuclease from cobra venom. In ion-exchange chromatography, ribonuclease is eluted in two fractions. The fraction with the highest specific activity has a molecular weight of 15900 and is homogeneous in 15 per cent polyacrilamide gel electrophoresis at pH 8.9. Electrophoresis at pH 4.3 reveals a minor fast component of this fraction which also exhibits a ribonuclease activity. Sulphoethylcellulose chromatography fairly separates cobra venom phosphodiesterase and 5'-nucleotidase eluted as a single fraction in gel chromatography."} {"id": "PMID:173424", "title": "[Activation of carbonic anhydrase from rat gastric tissue as a result of phosphorylation by 3',5'-AMP-dependent protein kinase].", "content": "Two isoenzymes of carbonic anhydrase, one with high activity and the other with low activity, were isolated from rat gastric tissue. It was found that both isoenzymes were phosphorylated in vitro by protein kinase isolated from gastric mucosa and that this process was stimulated by 3',5'-AMP. The phosphorylation of highly active carbonic anhydrase isoenzyme is shown to result in the increase of its activity. The phosphorylation of low active carbonic anhydrase isoenzyme did not affect its activity or decreased it slightly. The results obtained suggest that the activation of carbonic anhydrase in vivo by gastrin (pentagastrin), histamine and 3',5'-AMP is due to the phosphorylation of highly active isoenzyme by 3',5-AMP-dependent protein kinase. It seems possible that in this process histamine and 3',5'-AMP act as sequential mediators of pentagastrin effect.", "contents": "[Activation of carbonic anhydrase from rat gastric tissue as a result of phosphorylation by 3',5'-AMP-dependent protein kinase]. Two isoenzymes of carbonic anhydrase, one with high activity and the other with low activity, were isolated from rat gastric tissue. It was found that both isoenzymes were phosphorylated in vitro by protein kinase isolated from gastric mucosa and that this process was stimulated by 3',5'-AMP. The phosphorylation of highly active carbonic anhydrase isoenzyme is shown to result in the increase of its activity. The phosphorylation of low active carbonic anhydrase isoenzyme did not affect its activity or decreased it slightly. The results obtained suggest that the activation of carbonic anhydrase in vivo by gastrin (pentagastrin), histamine and 3',5'-AMP is due to the phosphorylation of highly active isoenzyme by 3',5-AMP-dependent protein kinase. It seems possible that in this process histamine and 3',5'-AMP act as sequential mediators of pentagastrin effect."} {"id": "PMID:173428", "title": "[Effect of bradkinin-potentiating snake venom peptides and C-terminal pentapeptide fragment of bradkinin on carboxypeptidase N and kiniase activities of human blood serum].", "content": "Effects of bradikinin-potentiating peptides (BPP5a and BPPB), which are identical to peptides from Bothrops jararaca and Agkistrodon halys blomhoffii snake venom, and pentapeptide C-terminal bradikinin fragment on carboxypeptidase N and kinase activities in human blood serum are studied. It is found that BPP5a and BPPB at concentrations of 5-10(-4) M and 2.5-10(-4) M respectively do not inhibit the hydrolysis of hippuryl-L-lysine and hippuryl-L-argininic acid by carboxypeptidase N and at a concentration of 2-10(-3) M they do not affect the rate of the release of C-terminal arginine residue from bradikinin. BPP5a and BPPB do not inhibit the kininase activity of diluted human blood serum in vitro. Unlike BPP5a and BPPB, C-terminal pentapeptide bradikinin fragment is a competitive inhibitor of carboxypeptidase N, and it inhibits (at a concentration of 5-10(-4) M) the hydrolysis of hippuryl-L-lysine and hippuryl-L-argininic acid by 50%. It also inhibits the hydrolysis of bradikinin with diluted human blood serum. BPP5a and BPPB have an inconstant constriction effect on isolated rat uterus at concentration exceeding 4-6 orders the concentration of bradikinin. BPP5a at concentrations from 4-10(-9) to 4-10(-8) g/ml increases the sensitivity of rat uterus in 1.6--2.0 times.", "contents": "[Effect of bradkinin-potentiating snake venom peptides and C-terminal pentapeptide fragment of bradkinin on carboxypeptidase N and kiniase activities of human blood serum]. Effects of bradikinin-potentiating peptides (BPP5a and BPPB), which are identical to peptides from Bothrops jararaca and Agkistrodon halys blomhoffii snake venom, and pentapeptide C-terminal bradikinin fragment on carboxypeptidase N and kinase activities in human blood serum are studied. It is found that BPP5a and BPPB at concentrations of 5-10(-4) M and 2.5-10(-4) M respectively do not inhibit the hydrolysis of hippuryl-L-lysine and hippuryl-L-argininic acid by carboxypeptidase N and at a concentration of 2-10(-3) M they do not affect the rate of the release of C-terminal arginine residue from bradikinin. BPP5a and BPPB do not inhibit the kininase activity of diluted human blood serum in vitro. Unlike BPP5a and BPPB, C-terminal pentapeptide bradikinin fragment is a competitive inhibitor of carboxypeptidase N, and it inhibits (at a concentration of 5-10(-4) M) the hydrolysis of hippuryl-L-lysine and hippuryl-L-argininic acid by 50%. It also inhibits the hydrolysis of bradikinin with diluted human blood serum. BPP5a and BPPB have an inconstant constriction effect on isolated rat uterus at concentration exceeding 4-6 orders the concentration of bradikinin. BPP5a at concentrations from 4-10(-9) to 4-10(-8) g/ml increases the sensitivity of rat uterus in 1.6--2.0 times."} {"id": "PMID:173427", "title": "[Isolation of exonuclease A5 preparation free of phosphomonoesterase contamination].", "content": "A method is described of the isolation of exonuclease from cultural medium of Actinomyces sp. of coelicolor type, strain 5. The enzyme preparation is practically free from phosphatase activity (the ratio between exonuclease and phosphatase activities is about 10000). Chromatography on DEAE-Sephadex after the heating of the enzyme preparation at 37 degrees C and pH 5.5 in the presence of 2-mercaptoethanol was used to elimate the phosphatase contamination. The preparation of exonuclease A5 is suitable for different structural studies of nucleic acids, it can be used (instead of snake venom PDE) in a large scale preparation of 5'-mononucleotides from nucleic acids as well.", "contents": "[Isolation of exonuclease A5 preparation free of phosphomonoesterase contamination]. A method is described of the isolation of exonuclease from cultural medium of Actinomyces sp. of coelicolor type, strain 5. The enzyme preparation is practically free from phosphatase activity (the ratio between exonuclease and phosphatase activities is about 10000). Chromatography on DEAE-Sephadex after the heating of the enzyme preparation at 37 degrees C and pH 5.5 in the presence of 2-mercaptoethanol was used to elimate the phosphatase contamination. The preparation of exonuclease A5 is suitable for different structural studies of nucleic acids, it can be used (instead of snake venom PDE) in a large scale preparation of 5'-mononucleotides from nucleic acids as well."} {"id": "PMID:173439", "title": "Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison.", "content": "The functional significance of granule enzymes in polymorphonuclear leukocytes (PMN) is not fully understood because of the multiplicity of the enzymes and the rare occurrence of deficiencies in man. In order to select appropriate laboratory animals for functional studies, a phylogenetic comparison of enzyme levels in animal and human PMN was undertaken. Neutrophils were obtained from a variety of laboratory animals and man; the activities of alkaline phosphatase, lysozyme, myeloperoxidase, and beta-glucuronidase were determined by histochemical and analytical techniques. Marked interspecies differences in enzyme activity were found; many species were deficient in alkaline phosphatase or lysozyme. Differences in pH optima and metal requirements of alkaline phosphatase were not of sufficient magnitude to explain the variations of this enzyme.", "contents": "Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison. The functional significance of granule enzymes in polymorphonuclear leukocytes (PMN) is not fully understood because of the multiplicity of the enzymes and the rare occurrence of deficiencies in man. In order to select appropriate laboratory animals for functional studies, a phylogenetic comparison of enzyme levels in animal and human PMN was undertaken. Neutrophils were obtained from a variety of laboratory animals and man; the activities of alkaline phosphatase, lysozyme, myeloperoxidase, and beta-glucuronidase were determined by histochemical and analytical techniques. Marked interspecies differences in enzyme activity were found; many species were deficient in alkaline phosphatase or lysozyme. Differences in pH optima and metal requirements of alkaline phosphatase were not of sufficient magnitude to explain the variations of this enzyme."} {"id": "PMID:173440", "title": "Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia.", "content": "Humans and grey collie dogs with cyclic neutropenia are known to suffer from an increased rate of bacterial infection. Because of the previously described microanatomic abnormalities of lysosome formation found in the polymorphonuclear leukocytes (PMNs) of dogs with canine cyclic neutropenia, studies of these cells were undertaken. PMNs from grey collie dogs were found to have significant metabolic and functional abnormalities when compared with normal collie PMNs. These included abnormally increased postphagocytic C1-glucose oxidation, decreased iodination of trichloroacetic acid-precipitable protein in the resting and phagocytizing state, decreased levels of intracellular myeloperoxidase,and a bactericidal defect against a variety of bacteria. Phagocytosis was normal. These abnormalities appear to differ from those previously described in the PMNs of patients with chronic granulomatous disease of childhood and the Chediak-Higashi syndrome and more closely resemble those seen in hereditary myeloperoxidase deficiency. Thus, the studies reported here demonstrate defective PMN function in a disease state previously believed to be a model only of periodic hematopoiesis.", "contents": "Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia. Humans and grey collie dogs with cyclic neutropenia are known to suffer from an increased rate of bacterial infection. Because of the previously described microanatomic abnormalities of lysosome formation found in the polymorphonuclear leukocytes (PMNs) of dogs with canine cyclic neutropenia, studies of these cells were undertaken. PMNs from grey collie dogs were found to have significant metabolic and functional abnormalities when compared with normal collie PMNs. These included abnormally increased postphagocytic C1-glucose oxidation, decreased iodination of trichloroacetic acid-precipitable protein in the resting and phagocytizing state, decreased levels of intracellular myeloperoxidase,and a bactericidal defect against a variety of bacteria. Phagocytosis was normal. These abnormalities appear to differ from those previously described in the PMNs of patients with chronic granulomatous disease of childhood and the Chediak-Higashi syndrome and more closely resemble those seen in hereditary myeloperoxidase deficiency. Thus, the studies reported here demonstrate defective PMN function in a disease state previously believed to be a model only of periodic hematopoiesis."} {"id": "PMID:173441", "title": "Multiple myeloma with intramedullary masses of M-component.", "content": "The bone marrow of a patient with light chain myeloma and amyloidosis was substantially infiltrated with basophilic globular particles. The globules, which were confined to the bone marrow, ranged in size from tiny intracytoplasmic inclusions to large (100 mu) extracellular particles. Both the intra- and extracellular globules stained with fluorescent antibody directed against the light chain (kappa) produced by the patient's abnormal clone, and not with other fluorescent antiserums. By electron microscopy, even the largest extracytophasmic globules were bounded at least in part by rough membranes, suggesting that their extreme size was the result of cellular synthesis rather than extracellular coalescence.", "contents": "Multiple myeloma with intramedullary masses of M-component. The bone marrow of a patient with light chain myeloma and amyloidosis was substantially infiltrated with basophilic globular particles. The globules, which were confined to the bone marrow, ranged in size from tiny intracytoplasmic inclusions to large (100 mu) extracellular particles. Both the intra- and extracellular globules stained with fluorescent antibody directed against the light chain (kappa) produced by the patient's abnormal clone, and not with other fluorescent antiserums. By electron microscopy, even the largest extracytophasmic globules were bounded at least in part by rough membranes, suggesting that their extreme size was the result of cellular synthesis rather than extracellular coalescence."} {"id": "PMID:173443", "title": "[Influence of the pituitary-adrenal axis on the brown fat tissue of the rat and golden hamster].", "content": "The suppression or reduction of the adrenal secretion in the Rat and in the golden Hamster results in a reduction of the weight of brown adipose tissue and of the volume of intra cytoplasmic vacuoles. When corticotropin is given to normal and hypophysectomized animals, the intra cytoplasmic vacuolar system and the corticosterone concentration of brown fat increase. After sham hypophysectomy and short ether intake, a considerable lipidic depletion and a high level of corticosterone are observed. The authors speculate that the by adrenaline. The morphologic responses are much more intense and rapid lipid content of brown adipose tissue is increased by corticotropin and reduced by adrenaline. The morphologic responses are much more intense and rapid in brown adipose tissue than in white adipose tissue.", "contents": "[Influence of the pituitary-adrenal axis on the brown fat tissue of the rat and golden hamster]. The suppression or reduction of the adrenal secretion in the Rat and in the golden Hamster results in a reduction of the weight of brown adipose tissue and of the volume of intra cytoplasmic vacuoles. When corticotropin is given to normal and hypophysectomized animals, the intra cytoplasmic vacuolar system and the corticosterone concentration of brown fat increase. After sham hypophysectomy and short ether intake, a considerable lipidic depletion and a high level of corticosterone are observed. The authors speculate that the by adrenaline. The morphologic responses are much more intense and rapid lipid content of brown adipose tissue is increased by corticotropin and reduced by adrenaline. The morphologic responses are much more intense and rapid in brown adipose tissue than in white adipose tissue."} {"id": "PMID:173444", "title": "The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.", "content": "1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug.", "contents": "The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration. 1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug."} {"id": "PMID:173445", "title": "In situ intraduct carcinoma of the breast: a long term follow-up study.", "content": "Twenty-eight patients with in situ intraduct carcinoma of the breast are reviewed. Two patients had bilateral tumours. The numbers of patients treated by wide local excision, simple mastectomy and mastectomy with axillary dissection were approximately equal; none of these patients died of carcinoma. The conclusions regarding prognosis and treatment of in situ intraduct carcinoma of the breast are discussed.", "contents": "In situ intraduct carcinoma of the breast: a long term follow-up study. Twenty-eight patients with in situ intraduct carcinoma of the breast are reviewed. Two patients had bilateral tumours. The numbers of patients treated by wide local excision, simple mastectomy and mastectomy with axillary dissection were approximately equal; none of these patients died of carcinoma. The conclusions regarding prognosis and treatment of in situ intraduct carcinoma of the breast are discussed."} {"id": "PMID:173448", "title": "Weight gain and the sleeping electroencephalogram: study of 10 patients with anorexia nervosa.", "content": "The relation between reduced nutritional intake, with consequent weight loss, and sleep disturbance was studied by comparing certain sleep encephalogram patterns in a group of inpatients with anorexia nervosa before, during, and after a regimen of refeeding with a normal diet to a matched population mean weight. At low body weights patients had less sleep and more restlessness, especially in the last four hours of the night. During refeeding and weight gain slow-wave sleep initially increased and then tended to decrease during the final stage of restoration of weight back to matched population mean levels. With the overall weight gain, however, there was a significant increase in length of sleep and rapid eye movement sleep, the latter increasing especially during the later stages of weight gain. These results reaffirm that insomnia, and especially early morning waking, is associated with low body weight in anorexia nervosa, and their implications are discussed with particular reference to a hypothetical association between various anabolic profiles and the need for differing components of sleep.", "contents": "Weight gain and the sleeping electroencephalogram: study of 10 patients with anorexia nervosa. The relation between reduced nutritional intake, with consequent weight loss, and sleep disturbance was studied by comparing certain sleep encephalogram patterns in a group of inpatients with anorexia nervosa before, during, and after a regimen of refeeding with a normal diet to a matched population mean weight. At low body weights patients had less sleep and more restlessness, especially in the last four hours of the night. During refeeding and weight gain slow-wave sleep initially increased and then tended to decrease during the final stage of restoration of weight back to matched population mean levels. With the overall weight gain, however, there was a significant increase in length of sleep and rapid eye movement sleep, the latter increasing especially during the later stages of weight gain. These results reaffirm that insomnia, and especially early morning waking, is associated with low body weight in anorexia nervosa, and their implications are discussed with particular reference to a hypothetical association between various anabolic profiles and the need for differing components of sleep."} {"id": "PMID:173450", "title": "Identification of radioactive 17beta-estradiol-17-beta-D-glucuronide and 17alpha-estradiol-17-beta-D-glucuronide in the urine of the domestic fowl after intramuscular injection of [4-14C]estrone.", "content": "Two previously uncharacterized radioactive estrogen conjugates, 17beta-estradiol-17-beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17beta-D-glucopyranosiduronate) and 17alpha-estradiol-17beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17alpha-yl-beta-D-glucopyranosiduronate), have been identified in small but significant amounts in avian urine and in a ratio of approximately 2:1 after intramuscular injection of [4-14C]estrone.", "contents": "Identification of radioactive 17beta-estradiol-17-beta-D-glucuronide and 17alpha-estradiol-17-beta-D-glucuronide in the urine of the domestic fowl after intramuscular injection of [4-14C]estrone. Two previously uncharacterized radioactive estrogen conjugates, 17beta-estradiol-17-beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17beta-D-glucopyranosiduronate) and 17alpha-estradiol-17beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17alpha-yl-beta-D-glucopyranosiduronate), have been identified in small but significant amounts in avian urine and in a ratio of approximately 2:1 after intramuscular injection of [4-14C]estrone."} {"id": "PMID:173451", "title": "Cysteine biosynthesis in Salmonella typhimurium: the presence of ATP-sulfurylase and APS-kinase in various cysteine-requiring mutants.", "content": "Enzymatic tests were performed on a series of cysteine-requiring mutants for the presence of the sulfate activating enzymes. ATP-sulfurylase (sulfate adenylyltransferase EC 2.7.7.4) and APS-kinase (adenylylsulfate kinase EC 2.7.1.25). The enzymatic products adenosine 5'-[35S]sulfatophosphate and adenosine 3'-phosphate 5'-[35S]sulfatophosphate were identified by paper electrophoresis and measured quantitatively without elution from the paper. Cys mutants mapping in cistrons, A, H, I, J, G, and Ea contain both enzymes. Mutation in the D cistron leads to the loss of ATP-sulfurylase. Mutants mapping in the C cistron lack APS-kinase. Ba, Bb, and Bc mutants lack both enzymes. The control of the synthesis of these enzymes by cysteine was examined. Both enzymes are missing when cells are grown on cysteine.", "contents": "Cysteine biosynthesis in Salmonella typhimurium: the presence of ATP-sulfurylase and APS-kinase in various cysteine-requiring mutants. Enzymatic tests were performed on a series of cysteine-requiring mutants for the presence of the sulfate activating enzymes. ATP-sulfurylase (sulfate adenylyltransferase EC 2.7.7.4) and APS-kinase (adenylylsulfate kinase EC 2.7.1.25). The enzymatic products adenosine 5'-[35S]sulfatophosphate and adenosine 3'-phosphate 5'-[35S]sulfatophosphate were identified by paper electrophoresis and measured quantitatively without elution from the paper. Cys mutants mapping in cistrons, A, H, I, J, G, and Ea contain both enzymes. Mutation in the D cistron leads to the loss of ATP-sulfurylase. Mutants mapping in the C cistron lack APS-kinase. Ba, Bb, and Bc mutants lack both enzymes. The control of the synthesis of these enzymes by cysteine was examined. Both enzymes are missing when cells are grown on cysteine."} {"id": "PMID:173452", "title": "Studies on adenylate cyclase-cyclic AMP system of the myopathic hamster (UM-X7.1) skeletal and cardiac muscles.", "content": "Cyclic AMP content, adenylate cyclase (EC 4.6.1.1) activity and phosphodiesterase I (EC 3.1.4.1) activity of the hind leg skeletal muscle and cardiac muscle in 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters were examined. In 60-day-old myopathic animals, cardiac cyclic AMP levels were higher and phosphodiesterase I activity was lower, without any changes in the basal adenylate cyclase activity, whereas in 150-day-old myopathic hamsters, cardiac cyclic AMP and basal adenylate cyclase activity were lower, without any changes in the homogenate phosphodiesterase I activity. On the other hand, basal adenylate cyclase and phosphodiesterase I activities in the skeletal muscle homogenate from 60- and 150-day-old myopathic animals were not different from the normal values but the skeletal muscle cyclic AMP levels were significantly less in 60-day-old myopathic hamsters only. The plasma cyclic AMP levels in 60-day-old myopathic hamsters, unlike 150-day-old myopathic animals, were higher than the normal. Although these results reveal differences in myopathic cardiac and skeletal muscles, it is concluded that changes in adenylate cyclase-cyclic AMP system in myopathy are dependent upon the degree of disease.", "contents": "Studies on adenylate cyclase-cyclic AMP system of the myopathic hamster (UM-X7.1) skeletal and cardiac muscles. Cyclic AMP content, adenylate cyclase (EC 4.6.1.1) activity and phosphodiesterase I (EC 3.1.4.1) activity of the hind leg skeletal muscle and cardiac muscle in 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters were examined. In 60-day-old myopathic animals, cardiac cyclic AMP levels were higher and phosphodiesterase I activity was lower, without any changes in the basal adenylate cyclase activity, whereas in 150-day-old myopathic hamsters, cardiac cyclic AMP and basal adenylate cyclase activity were lower, without any changes in the homogenate phosphodiesterase I activity. On the other hand, basal adenylate cyclase and phosphodiesterase I activities in the skeletal muscle homogenate from 60- and 150-day-old myopathic animals were not different from the normal values but the skeletal muscle cyclic AMP levels were significantly less in 60-day-old myopathic hamsters only. The plasma cyclic AMP levels in 60-day-old myopathic hamsters, unlike 150-day-old myopathic animals, were higher than the normal. Although these results reveal differences in myopathic cardiac and skeletal muscles, it is concluded that changes in adenylate cyclase-cyclic AMP system in myopathy are dependent upon the degree of disease."} {"id": "PMID:173453", "title": "Evidence for 16alpha-hydroxylation of estrone 3-sulphate by guinea pig liver slices.", "content": "[6,7-3H,35S]Estrone 3-sulfate (E13S) of 3H/35S = 3.57 was incubated with female guinea pig liver slices. Small amounts of free steroid and estrone-3-glucuronide, each containing 3H, were found. In addition, E13S, 17beta-estradiol 3-sulfate, and a 'disulfate' fraction, with 3H/35S = 4.4, 4.3, and 4.7, respectively, were also isolated from the incubated tissue. The latter fraction was a major metabolite and about 45% of it consisted of 'disulfates' of 16alpha-hydroxyestrone and estriol, thus providing strong evidence for 16alpha-hydroxylation in guinea pig liver slices.", "contents": "Evidence for 16alpha-hydroxylation of estrone 3-sulphate by guinea pig liver slices. [6,7-3H,35S]Estrone 3-sulfate (E13S) of 3H/35S = 3.57 was incubated with female guinea pig liver slices. Small amounts of free steroid and estrone-3-glucuronide, each containing 3H, were found. In addition, E13S, 17beta-estradiol 3-sulfate, and a 'disulfate' fraction, with 3H/35S = 4.4, 4.3, and 4.7, respectively, were also isolated from the incubated tissue. The latter fraction was a major metabolite and about 45% of it consisted of 'disulfates' of 16alpha-hydroxyestrone and estriol, thus providing strong evidence for 16alpha-hydroxylation in guinea pig liver slices."} {"id": "PMID:173455", "title": "The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4).", "content": "The inter-relationships of 32 pathologic and 7 clinical parameters encountered in the study of 1000 examples of invasive breast carcinoma have been presented. In some instances the biological significance of these associations is at present unclear. In others it is to be noted that there is no information provided as to the rank of their significance. Nevertheless, the associations that were encountered not only help further characterize the various forms of breast cancer but also provide information regarding the possible biological significance of some of their features. Although it is not our intention to minimize the possible significance of the inter-relationships of pathologic parameters, most emphasis in the summarizing statements which follow has been placed upon those correlations which may relate to prognosis. In this regard reference has been made to short-term treatment failure, vis a vis local recurrence and/or metastases, which may not necessarily accurately reflect patient survival, although generally such a relationship exists. Information in this regard as well as to the rank of the significance of these pathologic features shall be forthcoming when sufficient time has elapsed since the inception of this study to allow for such conclusions, i.e. survival or long-term treatment failure rates. Lastly, it becomes evident that the guidelines followed in the examination of these specimens appear to represent at least the minimum requirements necessary for a meaningful pathologic evaluation of breast carcinoma.", "contents": "The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4). The inter-relationships of 32 pathologic and 7 clinical parameters encountered in the study of 1000 examples of invasive breast carcinoma have been presented. In some instances the biological significance of these associations is at present unclear. In others it is to be noted that there is no information provided as to the rank of their significance. Nevertheless, the associations that were encountered not only help further characterize the various forms of breast cancer but also provide information regarding the possible biological significance of some of their features. Although it is not our intention to minimize the possible significance of the inter-relationships of pathologic parameters, most emphasis in the summarizing statements which follow has been placed upon those correlations which may relate to prognosis. In this regard reference has been made to short-term treatment failure, vis a vis local recurrence and/or metastases, which may not necessarily accurately reflect patient survival, although generally such a relationship exists. Information in this regard as well as to the rank of the significance of these pathologic features shall be forthcoming when sufficient time has elapsed since the inception of this study to allow for such conclusions, i.e. survival or long-term treatment failure rates. Lastly, it becomes evident that the guidelines followed in the examination of these specimens appear to represent at least the minimum requirements necessary for a meaningful pathologic evaluation of breast carcinoma."} {"id": "PMID:173456", "title": "Primary oat cell carcinoma of the larynx: an ultrastructural study.", "content": "An extrapulmonary oat cell carcinoma arising in the larynx is described. Ultrastructurally the tumor is identical to the oat cell carcinoma of pulmonary origin. The pressure of neurosecretory granules in our case strongly suggests that the tumor is derived from Kulchitsky-like cells, a histogenesis previously proposed for oat cell carcinoma of the lung.", "contents": "Primary oat cell carcinoma of the larynx: an ultrastructural study. An extrapulmonary oat cell carcinoma arising in the larynx is described. Ultrastructurally the tumor is identical to the oat cell carcinoma of pulmonary origin. The pressure of neurosecretory granules in our case strongly suggests that the tumor is derived from Kulchitsky-like cells, a histogenesis previously proposed for oat cell carcinoma of the lung."} {"id": "PMID:173457", "title": "Ultrastructural study of a postinflammatory \"tumor\" of the lung.", "content": "A typical postinflammatory \"tumor\" of the lung was resected from an asymptomatic 22-year-old white woman. Light and electron microscopic studies showed the lesion to be composed of metaplastic pneumonocytes, proliferated stroma, and chronic inflammatory cells. These findings confirm the inflammatory nature of the lesion and serve to distinguish this lesion from the neoplastic pulmonary sclerosing hemangioma.", "contents": "Ultrastructural study of a postinflammatory \"tumor\" of the lung. A typical postinflammatory \"tumor\" of the lung was resected from an asymptomatic 22-year-old white woman. Light and electron microscopic studies showed the lesion to be composed of metaplastic pneumonocytes, proliferated stroma, and chronic inflammatory cells. These findings confirm the inflammatory nature of the lesion and serve to distinguish this lesion from the neoplastic pulmonary sclerosing hemangioma."} {"id": "PMID:173458", "title": "Cellular immunity in neoplasia. Antigen and mitogen responses in patients with bronchiogenic carcinoma.", "content": "Cellular immune responses of patients with histologically confirmed lung carcinoma were assessed in vivo using cutaneous response and in vitro with a microlymphocyte blastogenic transformation (LBT) assay. In addition, correlation of the cutaneous response with the migration inhibitory factor (MIF) assay and LBT response was examined. The results indicated that cutaneous responses seen in patients with cancer of the lung were consistently lower than similar responses in normal controls (p less than 0.001). Similarily, the percentage of positive cutaneous responses seen with patients included in this study was lower than the frequencies reported by others. Stimulation of cells from lung cancer patients by PHA-M was also depressed when compared to similar lymphocytic responses in normal volunteers (p less than 0.001). The correlation between cutaneous response to tuberculin and the in vitro assays was high. The few instances of disparity demonstrate the need to utilize more than one assay in evaluating cellular immune functions. These data would support the work of others that indicate a depression of cellular immunity in advanced malignancy.", "contents": "Cellular immunity in neoplasia. Antigen and mitogen responses in patients with bronchiogenic carcinoma. Cellular immune responses of patients with histologically confirmed lung carcinoma were assessed in vivo using cutaneous response and in vitro with a microlymphocyte blastogenic transformation (LBT) assay. In addition, correlation of the cutaneous response with the migration inhibitory factor (MIF) assay and LBT response was examined. The results indicated that cutaneous responses seen in patients with cancer of the lung were consistently lower than similar responses in normal controls (p less than 0.001). Similarily, the percentage of positive cutaneous responses seen with patients included in this study was lower than the frequencies reported by others. Stimulation of cells from lung cancer patients by PHA-M was also depressed when compared to similar lymphocytic responses in normal volunteers (p less than 0.001). The correlation between cutaneous response to tuberculin and the in vitro assays was high. The few instances of disparity demonstrate the need to utilize more than one assay in evaluating cellular immune functions. These data would support the work of others that indicate a depression of cellular immunity in advanced malignancy."} {"id": "PMID:173459", "title": "The urinary excretion of corticosteroid sulfates by cancer patients.", "content": "Urinary excretions of free cortisol and corticosteroid sulfates were determined in 31 female controls, 77 breast cancer patients, 14 cases of colonic cancer, and 7 patients with bronchial carcinoma. Elevated corticosteroid sulfate excretion was present in 38% of patients with locally recurrent breast cancer and 30% of those with distant metastases, but in only 13% of the \"early\" breast cancer cases. A similar abnormality was seen in colonic cancer. Urinary free cortisol was usually normal. ACTH stimulation in a normal subject produced marked increases of both urinary free cortisol and corticosteroid sulfates. It is concluded that elevated corticosteroid sulfate excretion in cancer patients arises from an increased cortisol production rate combined with increased sulfurylation of the steroid. In bronchial carcinoma patients, changes similar to those occurring in the ACTH-treated normal subject may have resulted from ectopic ACTH production in the tumor.", "contents": "The urinary excretion of corticosteroid sulfates by cancer patients. Urinary excretions of free cortisol and corticosteroid sulfates were determined in 31 female controls, 77 breast cancer patients, 14 cases of colonic cancer, and 7 patients with bronchial carcinoma. Elevated corticosteroid sulfate excretion was present in 38% of patients with locally recurrent breast cancer and 30% of those with distant metastases, but in only 13% of the \"early\" breast cancer cases. A similar abnormality was seen in colonic cancer. Urinary free cortisol was usually normal. ACTH stimulation in a normal subject produced marked increases of both urinary free cortisol and corticosteroid sulfates. It is concluded that elevated corticosteroid sulfate excretion in cancer patients arises from an increased cortisol production rate combined with increased sulfurylation of the steroid. In bronchial carcinoma patients, changes similar to those occurring in the ACTH-treated normal subject may have resulted from ectopic ACTH production in the tumor."} {"id": "PMID:173460", "title": "Primary malignant fibrous histiocytoma of bone.", "content": "A review of over 400 primary bone tumors yielded 11 lesions with features allowing classification as malignant fibrous histiocytoma on a purely histological basis. Correlation with roentgenograms and clinical data indicated that these tumors occurred as osteolytic lesions associated with a high incidence of pathologic fractures in the metaphyses of skeletally mature long bones. Nine patients developed pulmonary metastases and 3 developed lymph node metastases within 21 months following diagnosis. The average survival was 12 months in 6 of the 9 patients who had no secondary treatment in their metastases. Treatment of 3 patients with metastatic lesions with chemotherapy or radiotherapy has been clinically encouraging. Some evidence was obtained that either or both the histiocytic and fibroblastic component may metastasize. There is a need for biopsy of metastatic lesions and autopsy followup to more accurately assess the mode of spread and histologic type of the metastases.", "contents": "Primary malignant fibrous histiocytoma of bone. A review of over 400 primary bone tumors yielded 11 lesions with features allowing classification as malignant fibrous histiocytoma on a purely histological basis. Correlation with roentgenograms and clinical data indicated that these tumors occurred as osteolytic lesions associated with a high incidence of pathologic fractures in the metaphyses of skeletally mature long bones. Nine patients developed pulmonary metastases and 3 developed lymph node metastases within 21 months following diagnosis. The average survival was 12 months in 6 of the 9 patients who had no secondary treatment in their metastases. Treatment of 3 patients with metastatic lesions with chemotherapy or radiotherapy has been clinically encouraging. Some evidence was obtained that either or both the histiocytic and fibroblastic component may metastasize. There is a need for biopsy of metastatic lesions and autopsy followup to more accurately assess the mode of spread and histologic type of the metastases."} {"id": "PMID:173461", "title": "Childhood Hodgkin's disease in Israel. A study of 17 cases.", "content": "A study of 17 children suffering from Hodgkin's disease (H.D.) is presented. The special ethnic distribution with predominance in Arab and Oriental Jewish children is noted. A high incidence of mixed cellularity histology in Arab children is emphasized. A conservative approach to therapy, i.e. extended field regional radiotherapy only, resulted in a long first complete remission period in lymphocyte predominance and nodular sclerosis H.D. Stages IA and IIA. All children in Stage IIIB and IV were treated by six courses of combined chemotherapy, and were maintained either on chlorambucil and vinblastine or on MOPP. Patients with mixed cellularity H.D. Stage IIA and all patients in Stage IIIA were treated by four courses of MOPP after the completion of extended regional radiotherapy. The 5 children who did not receive the schedules treatment died. The remaining 12 are well, with a survival of 8 to 104 months.", "contents": "Childhood Hodgkin's disease in Israel. A study of 17 cases. A study of 17 children suffering from Hodgkin's disease (H.D.) is presented. The special ethnic distribution with predominance in Arab and Oriental Jewish children is noted. A high incidence of mixed cellularity histology in Arab children is emphasized. A conservative approach to therapy, i.e. extended field regional radiotherapy only, resulted in a long first complete remission period in lymphocyte predominance and nodular sclerosis H.D. Stages IA and IIA. All children in Stage IIIB and IV were treated by six courses of combined chemotherapy, and were maintained either on chlorambucil and vinblastine or on MOPP. Patients with mixed cellularity H.D. Stage IIA and all patients in Stage IIIA were treated by four courses of MOPP after the completion of extended regional radiotherapy. The 5 children who did not receive the schedules treatment died. The remaining 12 are well, with a survival of 8 to 104 months."} {"id": "PMID:173462", "title": "Investigations on the turnover of adrenocortical mitochondria. III. Stereologic and autoradiographic observations on the effect of chronic treatment with dexamethasone on the rat Zona fasciculata mitochondria.", "content": "The effects of chronic administration of dexamethasone (for up to 15 consecutive days) on both the morphology and DNA-synthesis of the mitochondria of the rat adrenal zona fasciculata were investigated by stereologic and autoradiographic techniques. Up to the 3rd day of continuous dexamethasone treatment, the average volume of mitochondria did not change, whereas the number of mitochondria per cell was significantly decreased. From the 3rd to the 15th day of hormonal administration both the volume and number of mitochondria were found to decrease in proportion to the duration of treatment. Autoradiography showed that after the 3rd day of dexamethasone administration there is virtually no incorporation of 3H-thymidine into the mitochondrial compartment. These findings are discussed in the light of evidence indicating that dexamethasone blocks ACTH-release by inhibiting the hypothalamo-hypophyseal axis. The results confirm the view that ACTH controls the maintenance of growth and proliferation of rat adrenocortical mitochondria.", "contents": "Investigations on the turnover of adrenocortical mitochondria. III. Stereologic and autoradiographic observations on the effect of chronic treatment with dexamethasone on the rat Zona fasciculata mitochondria. The effects of chronic administration of dexamethasone (for up to 15 consecutive days) on both the morphology and DNA-synthesis of the mitochondria of the rat adrenal zona fasciculata were investigated by stereologic and autoradiographic techniques. Up to the 3rd day of continuous dexamethasone treatment, the average volume of mitochondria did not change, whereas the number of mitochondria per cell was significantly decreased. From the 3rd to the 15th day of hormonal administration both the volume and number of mitochondria were found to decrease in proportion to the duration of treatment. Autoradiography showed that after the 3rd day of dexamethasone administration there is virtually no incorporation of 3H-thymidine into the mitochondrial compartment. These findings are discussed in the light of evidence indicating that dexamethasone blocks ACTH-release by inhibiting the hypothalamo-hypophyseal axis. The results confirm the view that ACTH controls the maintenance of growth and proliferation of rat adrenocortical mitochondria."} {"id": "PMID:173463", "title": "The pituitary gland of the coelacanth fish Latimeria chalumnae Smith: general structure and adenohypophysial cell types.", "content": "The pituitary gland of Latimeria chalumnae is situated rostroventral to the telencephalon. The hollow pituitary stalk is bent forward and is ventrally connected to a saccus-vasculosus-like organ, rostrally to a neurointermediate lobe. The infundibular lumen protrudes far into the neurohypophysial lobules. The elongated principal part (pars cerebralis) of the pars distalis is partly embedded in a dorsal depression of the pars intermedia and caudally invaded by the neurohypophysis. It may be divided into rostral and proximal pars distalis and includes a ramified hypophysial cleft, which continues rostrally as a duct with adjacent islets of pars distalis tissue (parts of a pars buccalis). The adenohypophysis consists of cell cords and follicles. Eight tinctorial cell types can be distinguished: in the rostral islets: large basophils with acidophil globules, in the rostral pars distalis: small basophils, large basophils with amphiphil characters and erythrosin-, orange G-positive acidophils; in the proximal pars distalis: orange G-positive acidophils and small and large basophils, having similar staining properties; in the pars intermedia: one amphiphil cell type.", "contents": "The pituitary gland of the coelacanth fish Latimeria chalumnae Smith: general structure and adenohypophysial cell types. The pituitary gland of Latimeria chalumnae is situated rostroventral to the telencephalon. The hollow pituitary stalk is bent forward and is ventrally connected to a saccus-vasculosus-like organ, rostrally to a neurointermediate lobe. The infundibular lumen protrudes far into the neurohypophysial lobules. The elongated principal part (pars cerebralis) of the pars distalis is partly embedded in a dorsal depression of the pars intermedia and caudally invaded by the neurohypophysis. It may be divided into rostral and proximal pars distalis and includes a ramified hypophysial cleft, which continues rostrally as a duct with adjacent islets of pars distalis tissue (parts of a pars buccalis). The adenohypophysis consists of cell cords and follicles. Eight tinctorial cell types can be distinguished: in the rostral islets: large basophils with acidophil globules, in the rostral pars distalis: small basophils, large basophils with amphiphil characters and erythrosin-, orange G-positive acidophils; in the proximal pars distalis: orange G-positive acidophils and small and large basophils, having similar staining properties; in the pars intermedia: one amphiphil cell type."} {"id": "PMID:173464", "title": "Variability of the effects of serum-free medium, dibutyryl-cyclic AMP or theophylline on the morphology of cultured new-born rat astroblasts.", "content": "The effects of serum deprivation, of dibutyryl-cyclic AMP (dBcAMP) and of theophylline on the morphology of cultured new-born rat astroblasts have been studied using Eagle's basal medium (BME) or Eagle's minimum essential medium (MEM) as culture media. Serum deprivation had no effect on cells cultured in BME, while in MEM, deprivation induced a rapid morphological transformation involving the appearance of multiple processes. This phenomenon was rapidly reversible when serum was again added. In serum-supplemented BME, dB-cAMP (1 mM) and theophylline (1 mM) had no effect. In serum-supplement MEM, theophylline (1 mM) had no effect while dB-cAMP (1 mM) induced a slower and poorly reversible morphological alteration. On the other hand cells in serum-free BME showed multiple processes after addition of dB-cAMP (1 mM) or theophylline (1 mM). This rapid alteration was completely reversed either by removal of dB-cAMP and theophylline or by addition of serum.", "contents": "Variability of the effects of serum-free medium, dibutyryl-cyclic AMP or theophylline on the morphology of cultured new-born rat astroblasts. The effects of serum deprivation, of dibutyryl-cyclic AMP (dBcAMP) and of theophylline on the morphology of cultured new-born rat astroblasts have been studied using Eagle's basal medium (BME) or Eagle's minimum essential medium (MEM) as culture media. Serum deprivation had no effect on cells cultured in BME, while in MEM, deprivation induced a rapid morphological transformation involving the appearance of multiple processes. This phenomenon was rapidly reversible when serum was again added. In serum-supplemented BME, dB-cAMP (1 mM) and theophylline (1 mM) had no effect. In serum-supplement MEM, theophylline (1 mM) had no effect while dB-cAMP (1 mM) induced a slower and poorly reversible morphological alteration. On the other hand cells in serum-free BME showed multiple processes after addition of dB-cAMP (1 mM) or theophylline (1 mM). This rapid alteration was completely reversed either by removal of dB-cAMP and theophylline or by addition of serum."} {"id": "PMID:173465", "title": "Monoamine fluorescence in the median eminence of the Japanese quail, Coturnix coturnix japonica, following medial basal hypothalamic deafferentation.", "content": "Monoamine fluorescence was examined in the ventral hypothalamus of the Japanese quail, Coturnix coturnix japonica after medial basal hypothalamic deafferentation. In sham-operated control birds, numerous yellow-green fluorescent fibers were observed in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, a number of fluorescent fibers and cell bodies were observed. In birds with deafferented hypothalami, fluorescence disappeared both in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, which was within the area of deafferentation, fluorescence of neuronal perikarya did not change, but fluorescent fibers decreased markedly in number. Disappearance of monoamine fluorescence in the median eminence and the nucleus tuberis is discussed in relation to the tanycyte absorptive function and gonadaly development.", "contents": "Monoamine fluorescence in the median eminence of the Japanese quail, Coturnix coturnix japonica, following medial basal hypothalamic deafferentation. Monoamine fluorescence was examined in the ventral hypothalamus of the Japanese quail, Coturnix coturnix japonica after medial basal hypothalamic deafferentation. In sham-operated control birds, numerous yellow-green fluorescent fibers were observed in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, a number of fluorescent fibers and cell bodies were observed. In birds with deafferented hypothalami, fluorescence disappeared both in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, which was within the area of deafferentation, fluorescence of neuronal perikarya did not change, but fluorescent fibers decreased markedly in number. Disappearance of monoamine fluorescence in the median eminence and the nucleus tuberis is discussed in relation to the tanycyte absorptive function and gonadaly development."} {"id": "PMID:173466", "title": "Subcellular compartmentation of free and esterified cholesterol in the interstitial cells of the mouse testis.", "content": "The subcellular distribution of free and esterified cholesterol in mouse testis and the changes occurring in cholesterol content of whole testes and cell fractions after inhibition of gonadotropins with methallibure (ICI 33, 828) and restimulation with human chorionic gonadotropin (HCG) are reported in the present paper. In subcellular fractions, the bulk of free cholesterol is associated with organelles sedimented in the microsomal fraction while esterified cholesterol is mainly stored in isolated lipid droplets. The latter compartment increases in methallibure-treated mice 2.3 fold and is remarkably depleted after administration of HCG. There is a close parallelism between the changes in esterified cholesterol content and the variation in the numbers of lipid droplets found in electron micrographs of interstitial cells of mice receiving similar treatments. By contrast no significant changes were noticed in either free cholesterol concentrations of the microsomal fractions or in the fine structure of organelles associated with this fraction. The dynamic nature of steroidogenesis in the microsomal fraction requires the existence of a free cholesterol pool with a high turnover rate for use as an intermediate in androgen synthesis. On the other hand, the large content of free cholesterol in microsomes and its stability under different conditions suggest the presence of a cholesterol compartment with a slow turnover, as a constituent of the membranes.", "contents": "Subcellular compartmentation of free and esterified cholesterol in the interstitial cells of the mouse testis. The subcellular distribution of free and esterified cholesterol in mouse testis and the changes occurring in cholesterol content of whole testes and cell fractions after inhibition of gonadotropins with methallibure (ICI 33, 828) and restimulation with human chorionic gonadotropin (HCG) are reported in the present paper. In subcellular fractions, the bulk of free cholesterol is associated with organelles sedimented in the microsomal fraction while esterified cholesterol is mainly stored in isolated lipid droplets. The latter compartment increases in methallibure-treated mice 2.3 fold and is remarkably depleted after administration of HCG. There is a close parallelism between the changes in esterified cholesterol content and the variation in the numbers of lipid droplets found in electron micrographs of interstitial cells of mice receiving similar treatments. By contrast no significant changes were noticed in either free cholesterol concentrations of the microsomal fractions or in the fine structure of organelles associated with this fraction. The dynamic nature of steroidogenesis in the microsomal fraction requires the existence of a free cholesterol pool with a high turnover rate for use as an intermediate in androgen synthesis. On the other hand, the large content of free cholesterol in microsomes and its stability under different conditions suggest the presence of a cholesterol compartment with a slow turnover, as a constituent of the membranes."} {"id": "PMID:173468", "title": "Isolation of the plasma membrane from sea urchin embryos.", "content": "A method for isolation of sea urchin embryos plasma membranes is described. Purification of the obtained fraction was assayed by several enzymatic markers and electron microscopy. The isolated plasma membranes appear to be pure from contamination of other cell membranes (endoplasmic reticulum and mitochondria), and they can therefore be used for analytical studies on the composition and structure of plasma membrane.", "contents": "Isolation of the plasma membrane from sea urchin embryos. A method for isolation of sea urchin embryos plasma membranes is described. Purification of the obtained fraction was assayed by several enzymatic markers and electron microscopy. The isolated plasma membranes appear to be pure from contamination of other cell membranes (endoplasmic reticulum and mitochondria), and they can therefore be used for analytical studies on the composition and structure of plasma membrane."} {"id": "PMID:173476", "title": "Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) in low renin and normal renin essential hypertension.", "content": "Insulin-induced hypoglycemia previously has been shown to provoke a beta-adrenergic response that normally results in an increase in plasma renin activity (PRA). In our study, hypoglycemia induced definite increases in PRA in a group of five patients with normal renin essential hypertension but failed to do so in a group of six patients with low renin essential hypertension. In both groups, plasma cyclic adenosine 3',5'-monophosphate (cyclic AMP; cAMP) increased more than 2-fold during hypoglycemia, but the response in the low renin group was significantly less than that previously observed in normal subjects under the same conditions. Plasma cortisol increased to an equal extent in both groups of hypertensive patients during hypoglycemia. Infusion of the phosphodiesterase inhibitor, theophylline, resulted in definite increases of PRA in patients with normal renin hypertension but not in patients with low renin hypertension. Because changes in the level of plasma cAMP during hypoglycemia have been thought to reflect adrenal catecholamine release, our finding of a blunted increase in plasma cAMP during hypoglycemia in patients with low renin hypertension may suggest that there is a generalized alteration in adrenergic responsiveness in this condition.", "contents": "Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) in low renin and normal renin essential hypertension. Insulin-induced hypoglycemia previously has been shown to provoke a beta-adrenergic response that normally results in an increase in plasma renin activity (PRA). In our study, hypoglycemia induced definite increases in PRA in a group of five patients with normal renin essential hypertension but failed to do so in a group of six patients with low renin essential hypertension. In both groups, plasma cyclic adenosine 3',5'-monophosphate (cyclic AMP; cAMP) increased more than 2-fold during hypoglycemia, but the response in the low renin group was significantly less than that previously observed in normal subjects under the same conditions. Plasma cortisol increased to an equal extent in both groups of hypertensive patients during hypoglycemia. Infusion of the phosphodiesterase inhibitor, theophylline, resulted in definite increases of PRA in patients with normal renin hypertension but not in patients with low renin hypertension. Because changes in the level of plasma cAMP during hypoglycemia have been thought to reflect adrenal catecholamine release, our finding of a blunted increase in plasma cAMP during hypoglycemia in patients with low renin hypertension may suggest that there is a generalized alteration in adrenergic responsiveness in this condition."} {"id": "PMID:173477", "title": "Combined para-aminosalicylic acid and dietary therapy in long-term control of hypercholesterolemia and hypertriglyceridemia (Types IIa and IIb hyperlipoproteinemia).", "content": "The hypolipidemic effect of PAS-C-diet treatment was studied in 63 patients with Types IIa and IIb hyperlipoproteinemia for 6-36 months. Serum lipids and body weights of all patients were stabilized by a low cholesterol-saturated fat-refined carbohydrate diet before the initiation of an eight-week placebo-drug single-blind crossover study. During the placebo period the plasma lipids levels, mean +/- SD: cholesterol 355 +/- 63.5 mg%, triglyceride 141 +/- 68.7 mg%, and LDL-cholesterol 279 +/- 56.8 mg% were lowered to 274 +/- 53.1 mg+, 98 +/- 40.6 mg%, and 209 +/- 52.9 mg%, respectively (P less than 0.001 in each instance), with 7.5-11.0 grams of PAS-C/day given in one to three divided doses. In ten patients who have completed three years of treatment similar results were obtained. They showed no tendency to develop drug tolerance. Eight had watery diarrhea during the initial period which promptly subsided with interruption of drug therapy. Reintroduction of PAS-C in smaller dose (4.5 g/day) with gradual increment to effective dosage level was tolerated by all. No hematologic, hepatic, and ophthalmologic abnormalities were demonstrated by periodic monitoring. The hypoplipidemic effect of the drug was found to be diminished by alcohol and caloric excess.", "contents": "Combined para-aminosalicylic acid and dietary therapy in long-term control of hypercholesterolemia and hypertriglyceridemia (Types IIa and IIb hyperlipoproteinemia). The hypolipidemic effect of PAS-C-diet treatment was studied in 63 patients with Types IIa and IIb hyperlipoproteinemia for 6-36 months. Serum lipids and body weights of all patients were stabilized by a low cholesterol-saturated fat-refined carbohydrate diet before the initiation of an eight-week placebo-drug single-blind crossover study. During the placebo period the plasma lipids levels, mean +/- SD: cholesterol 355 +/- 63.5 mg%, triglyceride 141 +/- 68.7 mg%, and LDL-cholesterol 279 +/- 56.8 mg% were lowered to 274 +/- 53.1 mg+, 98 +/- 40.6 mg%, and 209 +/- 52.9 mg%, respectively (P less than 0.001 in each instance), with 7.5-11.0 grams of PAS-C/day given in one to three divided doses. In ten patients who have completed three years of treatment similar results were obtained. They showed no tendency to develop drug tolerance. Eight had watery diarrhea during the initial period which promptly subsided with interruption of drug therapy. Reintroduction of PAS-C in smaller dose (4.5 g/day) with gradual increment to effective dosage level was tolerated by all. No hematologic, hepatic, and ophthalmologic abnormalities were demonstrated by periodic monitoring. The hypoplipidemic effect of the drug was found to be diminished by alcohol and caloric excess."} {"id": "PMID:173478", "title": "Serum beta -- lipoproteins: studies in a patient and in guinea pigs after the ingestion of organophosphorus compounds.", "content": "A patient admitted to this hospital with Parathion poisoning had a marked reduction in serum cholinesterase activity and concentration of low density lipoprotein. The enzyme and the lipoprotein levels returned to normal with clinical recovery. Guinea pigs treated with phospholine iodide showed depressed levels of serum cholinesterase and beta-lipoprotein. It is suggested that the decrease in beta-lipoproteins is due to the decrease in cholinesterase activity.", "contents": "Serum beta -- lipoproteins: studies in a patient and in guinea pigs after the ingestion of organophosphorus compounds. A patient admitted to this hospital with Parathion poisoning had a marked reduction in serum cholinesterase activity and concentration of low density lipoprotein. The enzyme and the lipoprotein levels returned to normal with clinical recovery. Guinea pigs treated with phospholine iodide showed depressed levels of serum cholinesterase and beta-lipoprotein. It is suggested that the decrease in beta-lipoproteins is due to the decrease in cholinesterase activity."} {"id": "PMID:173479", "title": "Enzymatic determinations of cholesterol in high-density-lipoprotein fractions prepared by a precipitation technique.", "content": "An enzymatic method for cholesterol in serum [Clin. Chem. 20, 470 (1974)] was initially found to be unsatisfactory for measuring cholesterol in high-density-lipoprotein fractions prepared by precipitation with Mn2+. A fine precipitate formed in the cuvette and cholesterol values were falsely increased. We describe a simple, convenient method for circumventing these problems. An ethylenediaminetetraacetate solution is used to reconstitute the enzymatic reagent. Cholesterol values by this procedure correlated with those obtained by the Lipid Research Clinic's procedure for the same lipoprotein fraction preparations (regression slope, .998; Y-intercept, 8.9 mg/liter; correlation coefficient, .984; standard error of the estimate, 16.8 mg/liter). Precision of the assay, including the precipitation step, was calculated. The SDwithin day was 9.7 mg/liter and SDoverall was 23.7 mg/liter. Results for total cholesterol with the modified reagent were linearly related to concentrations exceeding 4 g/liter, thereby permitting determination of high-density-lipoproteins and total cholesterol in a single run.", "contents": "Enzymatic determinations of cholesterol in high-density-lipoprotein fractions prepared by a precipitation technique. An enzymatic method for cholesterol in serum [Clin. Chem. 20, 470 (1974)] was initially found to be unsatisfactory for measuring cholesterol in high-density-lipoprotein fractions prepared by precipitation with Mn2+. A fine precipitate formed in the cuvette and cholesterol values were falsely increased. We describe a simple, convenient method for circumventing these problems. An ethylenediaminetetraacetate solution is used to reconstitute the enzymatic reagent. Cholesterol values by this procedure correlated with those obtained by the Lipid Research Clinic's procedure for the same lipoprotein fraction preparations (regression slope, .998; Y-intercept, 8.9 mg/liter; correlation coefficient, .984; standard error of the estimate, 16.8 mg/liter). Precision of the assay, including the precipitation step, was calculated. The SDwithin day was 9.7 mg/liter and SDoverall was 23.7 mg/liter. Results for total cholesterol with the modified reagent were linearly related to concentrations exceeding 4 g/liter, thereby permitting determination of high-density-lipoproteins and total cholesterol in a single run."} {"id": "PMID:173480", "title": "Inhibitory effect of ascorbic acid (vitamin C) on cortisol secretion following adrenal stimulation in children.", "content": "Measurements of plasma cortisol values before and at 4 and 6 hours after intramuscular administration of a depot preparation of synthetic b1-24 corticotrophin were carried out in 12 healthy children (group B) before, as well as on the 5th day of continuous ascorbic acid (AA) administration (1 g t.i.d. orally). Comparison of the results in group B with those of 8 healthy children similarly treated with corticotrophin but not given AA (group A) showed that, on the 5th day of AA administration the mean cortisol values after ACTH were significantly lower than the corresponding values in group A (p less than 0.02), or the post-ACTH values in group B observed on the 1st experimental day, i.e., before AA administration (p less than 0.001). On the other hand, AA administration had no significant effect on the fasting plasma cortisol values. These data suggest that AA excess following adrenal stimulation with ACTH exerts an inhibitory effect on cortisol secretion and consequently it may be of no benefit in conditions of stress.", "contents": "Inhibitory effect of ascorbic acid (vitamin C) on cortisol secretion following adrenal stimulation in children. Measurements of plasma cortisol values before and at 4 and 6 hours after intramuscular administration of a depot preparation of synthetic b1-24 corticotrophin were carried out in 12 healthy children (group B) before, as well as on the 5th day of continuous ascorbic acid (AA) administration (1 g t.i.d. orally). Comparison of the results in group B with those of 8 healthy children similarly treated with corticotrophin but not given AA (group A) showed that, on the 5th day of AA administration the mean cortisol values after ACTH were significantly lower than the corresponding values in group A (p less than 0.02), or the post-ACTH values in group B observed on the 1st experimental day, i.e., before AA administration (p less than 0.001). On the other hand, AA administration had no significant effect on the fasting plasma cortisol values. These data suggest that AA excess following adrenal stimulation with ACTH exerts an inhibitory effect on cortisol secretion and consequently it may be of no benefit in conditions of stress."} {"id": "PMID:173481", "title": "On the metabolism of lipoprotein-X (LP-X).", "content": "The characteristic low-density lipoprotein of cholestasis (LP-X) earlier described for humans is found with identical properties in dogs and rats after experimental cholestasis. After ligation of the common bile duct, LP-X may be detected in the plasma within the first 20 hours. A period of marked increase in concentration is followed by decreasing plasma concentrations and LP-X becomes undetectable 7-10 days after ligation of the bile duct in rats. High plasma bile salt concentration may alter the structural integrity of LP-X and may in part be responsible for its disappearance after long-lasting and severe biliary obstruction. Plasma decay curves for isolated LP-X injected intravenously into healthy animals revealed a rapid early fall in concentration followed by a gradual decline. The calculated fractional catabolic rate of LP-X was found to be 0.450 +/- 0.069 for dogs and 1.553 +/- 0.096 for rats corresponding to a mean biological half life of 37.7 +/- 6.4 h or 10.7 +/- 0.6 h, respectively. In vitro LP-X degradation occurs in post-heparin plasma, however, it seems to be too early to speculate on the enzyme activity and on the mode of action responsible for this disappearance.", "contents": "On the metabolism of lipoprotein-X (LP-X). The characteristic low-density lipoprotein of cholestasis (LP-X) earlier described for humans is found with identical properties in dogs and rats after experimental cholestasis. After ligation of the common bile duct, LP-X may be detected in the plasma within the first 20 hours. A period of marked increase in concentration is followed by decreasing plasma concentrations and LP-X becomes undetectable 7-10 days after ligation of the bile duct in rats. High plasma bile salt concentration may alter the structural integrity of LP-X and may in part be responsible for its disappearance after long-lasting and severe biliary obstruction. Plasma decay curves for isolated LP-X injected intravenously into healthy animals revealed a rapid early fall in concentration followed by a gradual decline. The calculated fractional catabolic rate of LP-X was found to be 0.450 +/- 0.069 for dogs and 1.553 +/- 0.096 for rats corresponding to a mean biological half life of 37.7 +/- 6.4 h or 10.7 +/- 0.6 h, respectively. In vitro LP-X degradation occurs in post-heparin plasma, however, it seems to be too early to speculate on the enzyme activity and on the mode of action responsible for this disappearance."} {"id": "PMID:173482", "title": "A rapid, enzymatic assay for measurement of inorganic pyrophosphate in biological samples.", "content": "An enzymatic assay for measurement of inorganic pyrophosphate (PPi) in biological samples is described using the UDPG pyrophosphorylase reaction and coupling it with three other enzymes in a system of phosphorylation and double reduction to form NADPH, which is measured fluorometrically. The method is specific for PPi in the presence of inorganic orthophosphate and can be used on small volumes of deproteinized ultrafiltrates of fluids or cell extracts. The assay was used here to determine the concentration of PPi in human plasma and serum, and the intracellular content of PPi in human skin fibroblasts, chondrocytes, and red blood cells. The mean PPi concentration of plasma was found to be 2.72 +/- 0.14 muM (mumo/l +/- S.E.M.); for serum it was 6.09 +/- 0.36 muM. The range (95% confidence limits) was 2.14-3.30 muM for plasma and 4.62-7.51 muM for serum. The average intracellular PPi content (pmoles PPi per 10(6) cells +/- S.E.M.) was as follows: (a) skin fibroblasts, 332 +/- 66; (b) articular chondrocytes, 655 +/- 46; red blood cells, 1.74 +/- 0.28.", "contents": "A rapid, enzymatic assay for measurement of inorganic pyrophosphate in biological samples. An enzymatic assay for measurement of inorganic pyrophosphate (PPi) in biological samples is described using the UDPG pyrophosphorylase reaction and coupling it with three other enzymes in a system of phosphorylation and double reduction to form NADPH, which is measured fluorometrically. The method is specific for PPi in the presence of inorganic orthophosphate and can be used on small volumes of deproteinized ultrafiltrates of fluids or cell extracts. The assay was used here to determine the concentration of PPi in human plasma and serum, and the intracellular content of PPi in human skin fibroblasts, chondrocytes, and red blood cells. The mean PPi concentration of plasma was found to be 2.72 +/- 0.14 muM (mumo/l +/- S.E.M.); for serum it was 6.09 +/- 0.36 muM. The range (95% confidence limits) was 2.14-3.30 muM for plasma and 4.62-7.51 muM for serum. The average intracellular PPi content (pmoles PPi per 10(6) cells +/- S.E.M.) was as follows: (a) skin fibroblasts, 332 +/- 66; (b) articular chondrocytes, 655 +/- 46; red blood cells, 1.74 +/- 0.28."} {"id": "PMID:173483", "title": "Action of metabolic inhibitors on the release of intracellular enzymes from human and rat lymphocytes and human erythrocytes.", "content": "A number of inhibitors of glycolysis and uncouplers of oxidative phosphorylation have been shown to increase the leakage of intracellular enzymes from preparations of rat lymphocytes and human lymphocytes and erythrocytes. The effect of each reagent on all three cell preparations is reversed in the presence of ATP in the medium. ADP is somewhat less effective. AMP exerts a slight protective effect on the human cells, but causes an increase in enzyme efflux from the rat cells. This species difference appears to be related to the concentration of adenylate kinase activity in the cells. The results are interpreted as supporting the theory that membrane permeability to enzymes and other intracellular proteins is dependent upon the energy content of the cell.", "contents": "Action of metabolic inhibitors on the release of intracellular enzymes from human and rat lymphocytes and human erythrocytes. A number of inhibitors of glycolysis and uncouplers of oxidative phosphorylation have been shown to increase the leakage of intracellular enzymes from preparations of rat lymphocytes and human lymphocytes and erythrocytes. The effect of each reagent on all three cell preparations is reversed in the presence of ATP in the medium. ADP is somewhat less effective. AMP exerts a slight protective effect on the human cells, but causes an increase in enzyme efflux from the rat cells. This species difference appears to be related to the concentration of adenylate kinase activity in the cells. The results are interpreted as supporting the theory that membrane permeability to enzymes and other intracellular proteins is dependent upon the energy content of the cell."} {"id": "PMID:173484", "title": "Two cases of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) associated with hGH deficiency and marginal impairment of other hypothalamic-pituitary functions.", "content": "Plasma hGH response to provocative tests (insulin-induced hypoglycaemia and arginine infusion) appears normal in Turner's syndrome. Two cases are reported of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) with unusual absence of plasms hGH response to provocative tests (arginine infusion, insulin-induced hypoglycaemia). Study of other pituitary functions supports the view that a hypothalamic-pituitary impairment is present in these cases. In fact, in these cases we observed low values of gonadotrophin excretion and limited responses of plasma ACTH and plasma corticosteroids to provocative tests (insulin-induced hypoglycaemia, metopyrone). Moreover, markedly abnormal plasma TSH response to TRF was observed in Case 2. The results are discussed with reference to the significance of this rare association.", "contents": "Two cases of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) associated with hGH deficiency and marginal impairment of other hypothalamic-pituitary functions. Plasma hGH response to provocative tests (insulin-induced hypoglycaemia and arginine infusion) appears normal in Turner's syndrome. Two cases are reported of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) with unusual absence of plasms hGH response to provocative tests (arginine infusion, insulin-induced hypoglycaemia). Study of other pituitary functions supports the view that a hypothalamic-pituitary impairment is present in these cases. In fact, in these cases we observed low values of gonadotrophin excretion and limited responses of plasma ACTH and plasma corticosteroids to provocative tests (insulin-induced hypoglycaemia, metopyrone). Moreover, markedly abnormal plasma TSH response to TRF was observed in Case 2. The results are discussed with reference to the significance of this rare association."} {"id": "PMID:173485", "title": "Induction and in Vitro demonstration of cellular immunity to DNA and RNA viruses in guinea-pigs.", "content": "Guinea-pigs were immunized with different cells infected with vaccinia virus, herpes simplex virus type 1, herpesvirus saimiri, and the virus of vesicular stomatitis. Development of cellular immunity against these viruses was observed with transformation of blood and spleen lymphocytes and with the migration inhibition test using peritoneal exudate cells. Cellular immunity against vaccinia virus was first seen 6 days after the inoculation of cell-bound vaccinia virus by lymphocyte transformation. The avtivation of the vaccinia virus specific cellular immune response could be induced with tissue culturrus. Since infectious virus particles are not synthesized within this time period, it is likely that virus-induced antigens in the cell surface are active in production of cellular immunity. Vaccines from heterologous host cells were more effective inducers of an immune response than syngeneic cell cultures. For in vitro testing of cellular immunity to viruses, viral antigens could be used in both infective and inactivated form. Delayed hypersensitivity to viral antigens was always accompanied by immune reactions to the host cells used for virus propagation.", "contents": "Induction and in Vitro demonstration of cellular immunity to DNA and RNA viruses in guinea-pigs. Guinea-pigs were immunized with different cells infected with vaccinia virus, herpes simplex virus type 1, herpesvirus saimiri, and the virus of vesicular stomatitis. Development of cellular immunity against these viruses was observed with transformation of blood and spleen lymphocytes and with the migration inhibition test using peritoneal exudate cells. Cellular immunity against vaccinia virus was first seen 6 days after the inoculation of cell-bound vaccinia virus by lymphocyte transformation. The avtivation of the vaccinia virus specific cellular immune response could be induced with tissue culturrus. Since infectious virus particles are not synthesized within this time period, it is likely that virus-induced antigens in the cell surface are active in production of cellular immunity. Vaccines from heterologous host cells were more effective inducers of an immune response than syngeneic cell cultures. For in vitro testing of cellular immunity to viruses, viral antigens could be used in both infective and inactivated form. Delayed hypersensitivity to viral antigens was always accompanied by immune reactions to the host cells used for virus propagation."} {"id": "PMID:173486", "title": "E and EAC rosetting lymphocytes in patients with carcinoma of bronchus I. Some parameters of the test and of its prognostic significance.", "content": "Using peripheral blood lymphocytes separated by a Ficoll method and suspended in saline, means of 77-1% (s.d. 5-2) E rosettes (T lymphocytes) and 20-1% (s.d. 6-7) EAC rosettes (B lymphocytes) have been obtained with normal healthy donors. Poorer E-rosette formation resulted from higher centrifugation speeds during the washing of lymphocytes or erythrocytes, insufficient chilling, or rough handling. The presence of 5% albumin in the final mixture stabilized the rosettes and brought a constant subpopulation of B lymphocytes into rosetting. In patients with bronchial carcinoma who, at the time of diagnosis, had E-rosette percentages below 1 s.d. of the mean for normal donors, the length of survival was significantly shorter than in those with normal or high values. The same was true for those in whom null cells were detected. In each case the correlation effect was mainly found in the group of patients with squamous carcinoma.", "contents": "E and EAC rosetting lymphocytes in patients with carcinoma of bronchus I. Some parameters of the test and of its prognostic significance. Using peripheral blood lymphocytes separated by a Ficoll method and suspended in saline, means of 77-1% (s.d. 5-2) E rosettes (T lymphocytes) and 20-1% (s.d. 6-7) EAC rosettes (B lymphocytes) have been obtained with normal healthy donors. Poorer E-rosette formation resulted from higher centrifugation speeds during the washing of lymphocytes or erythrocytes, insufficient chilling, or rough handling. The presence of 5% albumin in the final mixture stabilized the rosettes and brought a constant subpopulation of B lymphocytes into rosetting. In patients with bronchial carcinoma who, at the time of diagnosis, had E-rosette percentages below 1 s.d. of the mean for normal donors, the length of survival was significantly shorter than in those with normal or high values. The same was true for those in whom null cells were detected. In each case the correlation effect was mainly found in the group of patients with squamous carcinoma."} {"id": "PMID:173487", "title": "Adverse reactions to Zn1-24 ACTH therapy associated with specific cellular immunity.", "content": "Lymphocyte transformation to 1-24ACTH, as assessed by the incorporation of tritiated thymidine, has been demonstrated to be associated with severe adverse reactions occurring in patients receiving a Zn-linked 1-24ACTH preparation (Tetra cosactrin depot, 'Synacthen'). Antibodies measured with an isotope-binding assay occurred commonly in all patients receiving therapy and did not correlate with adverse reactions. Lymphocyte transformation with the 1-24ACTH polypeptide, a part of the naturally occurring ACTH molecule, has not been previously recorded. The significance of antibodies and cell-mediated immunity to this polypeptide hormone is discussed.", "contents": "Adverse reactions to Zn1-24 ACTH therapy associated with specific cellular immunity. Lymphocyte transformation to 1-24ACTH, as assessed by the incorporation of tritiated thymidine, has been demonstrated to be associated with severe adverse reactions occurring in patients receiving a Zn-linked 1-24ACTH preparation (Tetra cosactrin depot, 'Synacthen'). Antibodies measured with an isotope-binding assay occurred commonly in all patients receiving therapy and did not correlate with adverse reactions. Lymphocyte transformation with the 1-24ACTH polypeptide, a part of the naturally occurring ACTH molecule, has not been previously recorded. The significance of antibodies and cell-mediated immunity to this polypeptide hormone is discussed."} {"id": "PMID:173488", "title": "The complement system in cryoglobulinaemia. Interaction with immunoglobulins and lipoproteins.", "content": "Serum from a patient with an IgM-lipoprotein cryoglobulin, both before and after removal of the cryoprecipitate at 0 degrees C, had extremely low levels of whole complement (C), C1, C4 and C2, while amounts of the remaining components were normal or only slightly reduced. The cryopredipitate, when added to fresh normal human serum, reproduced this pattern of C fixation. Separation of the patients's serum at 37 degrees C into its lipoprotein, IgG and IgM fractions revealed that the IgM alone would precipitate at 0 degrees C. This precipitation was unaffected by the patients's IgG, but was markedly enhanced by extremely small amounts of the patient's d less than 1-075 lipoprotein fraction or of homologous very low density lipoprotein (VLDL). Aggregation occurred even at 37 degrees C in the presence of VLDL. Fixation of semi-purified human C1 paralleled these results closely: it occurred with the patient's IgM alone at 0 degrees but not at 37 degrees C, while IgM in the presence of the patient's lipoprotein, or of VLDL from normal serum, fixed C1 strongly at 37 degrees as well as at 0 degrees C. Fab dimers and monomers prepared from the patient's IgM did not aggregate in the cold, even in the presence of lipoprotein, and did not inhibit the aggregation of intact IgM in the presence of VLDL, at any temperature. All three highly purified IgM cryoglobulins, and three of four IgG cryoglobulins, fixed C1 strongly. The IgG preparation which failed to fix C1 was the only one which had lost its cryoprecipitability during purification. Measurement of C3 or whole C levels may be an insensitive method for detecting C fixation in cryoglobulinaemia. It is suggested that analysis for C1, C4 or C2 should be employed instead.", "contents": "The complement system in cryoglobulinaemia. Interaction with immunoglobulins and lipoproteins. Serum from a patient with an IgM-lipoprotein cryoglobulin, both before and after removal of the cryoprecipitate at 0 degrees C, had extremely low levels of whole complement (C), C1, C4 and C2, while amounts of the remaining components were normal or only slightly reduced. The cryopredipitate, when added to fresh normal human serum, reproduced this pattern of C fixation. Separation of the patients's serum at 37 degrees C into its lipoprotein, IgG and IgM fractions revealed that the IgM alone would precipitate at 0 degrees C. This precipitation was unaffected by the patients's IgG, but was markedly enhanced by extremely small amounts of the patient's d less than 1-075 lipoprotein fraction or of homologous very low density lipoprotein (VLDL). Aggregation occurred even at 37 degrees C in the presence of VLDL. Fixation of semi-purified human C1 paralleled these results closely: it occurred with the patient's IgM alone at 0 degrees but not at 37 degrees C, while IgM in the presence of the patient's lipoprotein, or of VLDL from normal serum, fixed C1 strongly at 37 degrees as well as at 0 degrees C. Fab dimers and monomers prepared from the patient's IgM did not aggregate in the cold, even in the presence of lipoprotein, and did not inhibit the aggregation of intact IgM in the presence of VLDL, at any temperature. All three highly purified IgM cryoglobulins, and three of four IgG cryoglobulins, fixed C1 strongly. The IgG preparation which failed to fix C1 was the only one which had lost its cryoprecipitability during purification. Measurement of C3 or whole C levels may be an insensitive method for detecting C fixation in cryoglobulinaemia. It is suggested that analysis for C1, C4 or C2 should be employed instead."} {"id": "PMID:173489", "title": "Effect of oral contraceptives on plasma clearance.", "content": "The effects of chronic steroid contraceptive therapy on drug clearance from plasma were studied by using plasma antipyrine, phenylbutazone, and cholecalciferol half-lives in women. After 3 mo of oral steroid therapy (Norinyl, 2 mg; norethindrone + mestranol), the antipyrine half-life was increased in 3 of 6 subjects, phenylbutazone half-life was not consistently altered, and vitamin D3 half-life was increased in 3 of 4 patients. After 1 to 7 yr of oral steroid theraphy, the antipyrine half-life was longer while taking the contraceptive than when the contraceptive treatment was discontinued in 4 of 6 subjects, whereas that of phenylbutazone was not consistently altered.", "contents": "Effect of oral contraceptives on plasma clearance. The effects of chronic steroid contraceptive therapy on drug clearance from plasma were studied by using plasma antipyrine, phenylbutazone, and cholecalciferol half-lives in women. After 3 mo of oral steroid therapy (Norinyl, 2 mg; norethindrone + mestranol), the antipyrine half-life was increased in 3 of 6 subjects, phenylbutazone half-life was not consistently altered, and vitamin D3 half-life was increased in 3 of 4 patients. After 1 to 7 yr of oral steroid theraphy, the antipyrine half-life was longer while taking the contraceptive than when the contraceptive treatment was discontinued in 4 of 6 subjects, whereas that of phenylbutazone was not consistently altered."} {"id": "PMID:173490", "title": "Effects of repeated doses of scopolamine on the electroencephalographic stages of sleep in normal volunteers.", "content": "Single doses of scopolamine markedly alter sleep patterns in man. This study intended to evaluate the persistence of these changes during continued administration. The design consisted of a sequence of habituation, no-medication, saline (control), scopolamine (0.006 mg/kg intramuscularly 3 consecutive nights), and saline. The first dose of scopolamine markedly retarded the onset of stage rapid eye movement (REM) sleep (p less than 0.005) and diminished the total amount of REM sleep during the night (p less than 0.025). A decrease in total number of eye movements (p less than 0.05) and an increase in body movements (p less than 0.025) were also observed. Changes after the second dose of scopolamine were less marked but still significant. The third dose of scopolamine produced less marked changes than the preceding two. When compared with the first scopolamine night, the onset of stage REM was retarded to a lesser extent (p less than 0.05) and the total amount of REM sleep was increased (p less than 0.05). An increase in the duration of the first REM period was also observed. Rebound effects on the appearance of the first REM period (p less than 0.01), number of eye movements (p less than 0.001), total amount of REM sleep (p less than 0.01), and body movements were observed in the last saline night.", "contents": "Effects of repeated doses of scopolamine on the electroencephalographic stages of sleep in normal volunteers. Single doses of scopolamine markedly alter sleep patterns in man. This study intended to evaluate the persistence of these changes during continued administration. The design consisted of a sequence of habituation, no-medication, saline (control), scopolamine (0.006 mg/kg intramuscularly 3 consecutive nights), and saline. The first dose of scopolamine markedly retarded the onset of stage rapid eye movement (REM) sleep (p less than 0.005) and diminished the total amount of REM sleep during the night (p less than 0.025). A decrease in total number of eye movements (p less than 0.05) and an increase in body movements (p less than 0.025) were also observed. Changes after the second dose of scopolamine were less marked but still significant. The third dose of scopolamine produced less marked changes than the preceding two. When compared with the first scopolamine night, the onset of stage REM was retarded to a lesser extent (p less than 0.05) and the total amount of REM sleep was increased (p less than 0.05). An increase in the duration of the first REM period was also observed. Rebound effects on the appearance of the first REM period (p less than 0.01), number of eye movements (p less than 0.001), total amount of REM sleep (p less than 0.01), and body movements were observed in the last saline night."} {"id": "PMID:173491", "title": "Calcium balance in drug-induced osteomalacia: response to vitamin D.", "content": "The effect of oral vitamin D3 therapy on calcium balance was compared in 18 institutionalized subjects with drug-induced osteomalacia and in 18 similar subjects without osteomalacia. The subjects with osteomalacia were receiving standard doses of phenytoin and phenobarbital. Diagnosis of osteomalacia was based on low serum calcium and phosphorus, elevated alkaline phosphatase, and appropriate roentgenographic bone changes. The study group achieved positive calcium balance at approximately 975 IU of vitamin D3 per day, while the control group achieved positive calcium balance at approximately 380 IU of vitamin D3 per day. The difference is highly significant (p less than 0.001). These data support previous observations that the osteomalacia of patients receiving anticonvulsant drugs is related to the drugs and that these patients require supplemental doses of vitamin D.", "contents": "Calcium balance in drug-induced osteomalacia: response to vitamin D. The effect of oral vitamin D3 therapy on calcium balance was compared in 18 institutionalized subjects with drug-induced osteomalacia and in 18 similar subjects without osteomalacia. The subjects with osteomalacia were receiving standard doses of phenytoin and phenobarbital. Diagnosis of osteomalacia was based on low serum calcium and phosphorus, elevated alkaline phosphatase, and appropriate roentgenographic bone changes. The study group achieved positive calcium balance at approximately 975 IU of vitamin D3 per day, while the control group achieved positive calcium balance at approximately 380 IU of vitamin D3 per day. The difference is highly significant (p less than 0.001). These data support previous observations that the osteomalacia of patients receiving anticonvulsant drugs is related to the drugs and that these patients require supplemental doses of vitamin D."} {"id": "PMID:173492", "title": "Variations in thyroid function and sleep in healthy young men.", "content": "1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men. 2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day. 3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary. 4. The subjects' sleep at night was assessed by electro-encephalogram. In days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain.", "contents": "Variations in thyroid function and sleep in healthy young men. 1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men. 2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day. 3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary. 4. The subjects' sleep at night was assessed by electro-encephalogram. In days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain."} {"id": "PMID:173495", "title": "The diagnostic value of serial brain scanning.", "content": "A survey of the literature pertaining to several serial brain scanning procedures has been presented. These procedures include rapid brain imaging, sequential brain imaging, delayed from imaging, and follow-up brain imaging. Applications of these techniques to specific clinical problems have been stressed and the reported results reviewed. Thus, it has been indicated that rapid brain imaging is most useful in detecting lesions secondary to cerebrovascular disease but may also provide some helpful information pertaining to the differential diagnosis of other C.N.S. lesions demonstrated on subsequent static brain scans. Sequential brain imaging is a time-consuming adjunctive procedure which, however, can be extraordinarily helpful in a highly selected group of problem cases which present with relatively small lesions adjacent to normal anatomic structures which themselves have considerable radioactivity. Delayed brain imaging has the distinction of detecting the greatest number of intracranial lesions but is attended by tactical problems in maintaining an optimal patient flow through the department and also has the undesirable consequence of reduced information density and diminished image quality, unless greater radiation doses are injected. Follow-up brain imaging is useful in the differential diagnosis of cerebrovascular and neoplastic disease and in the assessment of effectiveness of radiation therapy.", "contents": "The diagnostic value of serial brain scanning. A survey of the literature pertaining to several serial brain scanning procedures has been presented. These procedures include rapid brain imaging, sequential brain imaging, delayed from imaging, and follow-up brain imaging. Applications of these techniques to specific clinical problems have been stressed and the reported results reviewed. Thus, it has been indicated that rapid brain imaging is most useful in detecting lesions secondary to cerebrovascular disease but may also provide some helpful information pertaining to the differential diagnosis of other C.N.S. lesions demonstrated on subsequent static brain scans. Sequential brain imaging is a time-consuming adjunctive procedure which, however, can be extraordinarily helpful in a highly selected group of problem cases which present with relatively small lesions adjacent to normal anatomic structures which themselves have considerable radioactivity. Delayed brain imaging has the distinction of detecting the greatest number of intracranial lesions but is attended by tactical problems in maintaining an optimal patient flow through the department and also has the undesirable consequence of reduced information density and diminished image quality, unless greater radiation doses are injected. Follow-up brain imaging is useful in the differential diagnosis of cerebrovascular and neoplastic disease and in the assessment of effectiveness of radiation therapy."} {"id": "PMID:173498", "title": "Radiation-enhanced murine sarcoma virus genome rescue activity.", "content": "Although the doses of X-ray (312-2,500 R) used for irradiation of cells caused impairment of DNA synthesis and cell replication, co-cultivation of X-irradiated MuLV- carrier cells with un-irradiated nonproducer cells of MSV-induced tumour resulted in as much as 20-fold increase in MSV retrieval compared with the un-irradiated control. The enhancement was apparent also as a 3-fold increase in the number of cells producing MSV (infectious centers) in the co-cultivation plate. This suggested that the MSV genome rescue efficiency in terms of MSV per cell, as well as the number of cells producing MSV, increased markedly. By uridine-3H-labeling and focus assay experiments, evidence was presented which suggested that an increase in MSV/MuLV ratio in the culture fluid of co-cultivation plates was obtained when the MuLV-carrier cells were pre-irradiated. By contrast, X-irradiation of the nonproducer cells prior to co-cultivation caused only reductions of MSV genome rescue efficiency. However, use of X-irradiated MuLV-carrier cells for co-cultivation with X-irradiated nonproducer cells restored this efficiency to some extent. The dose-survival curve of the nonproducer cells was not much different from those of the MuLV-carrier cells after X-irradiation. It was suggested that the viability of nonproducer cells was required for replication of MuLV transferred from the carrier cells and for subsequent MSV genome rescue.", "contents": "Radiation-enhanced murine sarcoma virus genome rescue activity. Although the doses of X-ray (312-2,500 R) used for irradiation of cells caused impairment of DNA synthesis and cell replication, co-cultivation of X-irradiated MuLV- carrier cells with un-irradiated nonproducer cells of MSV-induced tumour resulted in as much as 20-fold increase in MSV retrieval compared with the un-irradiated control. The enhancement was apparent also as a 3-fold increase in the number of cells producing MSV (infectious centers) in the co-cultivation plate. This suggested that the MSV genome rescue efficiency in terms of MSV per cell, as well as the number of cells producing MSV, increased markedly. By uridine-3H-labeling and focus assay experiments, evidence was presented which suggested that an increase in MSV/MuLV ratio in the culture fluid of co-cultivation plates was obtained when the MuLV-carrier cells were pre-irradiated. By contrast, X-irradiation of the nonproducer cells prior to co-cultivation caused only reductions of MSV genome rescue efficiency. However, use of X-irradiated MuLV-carrier cells for co-cultivation with X-irradiated nonproducer cells restored this efficiency to some extent. The dose-survival curve of the nonproducer cells was not much different from those of the MuLV-carrier cells after X-irradiation. It was suggested that the viability of nonproducer cells was required for replication of MuLV transferred from the carrier cells and for subsequent MSV genome rescue."} {"id": "PMID:173499", "title": "Anti-Epstein-Barr virus antibody in patients with cancer of various sites and control groups.", "content": "Sera collected from patients with nasopharyngeal carcinoma (NPC, 321 cases), cancer of the other sites (297 cases), diseases of the ear, nose and throat (64 cases) and neighborhood controls matched for age and sex (817 cases) were titrated for antibodies to Epstein-Barr virus (EBV) by the indirect immunofluorescence antibody technique. High anti-EBV antibody titers (greater than or equal to 1:640) were noted in 55% in patients with NPC but only less than 31% were noted for the other 3 groups. The differences in the distributions of anti-EBV antibodies are statistically significant. The geometric mean levels of the antibody titers were 1:342 for the patients with NPC but less than 1:178 for the other 3 control groups. The relative risks shows that more than 40 times higher risk for those with equal to or higher than 1:640 antibody titers than those with lower than 1:40. The patients with NPC also show for higher ridit scales than the other 3 groups. The etiology of NPC was discussed with our findings.", "contents": "Anti-Epstein-Barr virus antibody in patients with cancer of various sites and control groups. Sera collected from patients with nasopharyngeal carcinoma (NPC, 321 cases), cancer of the other sites (297 cases), diseases of the ear, nose and throat (64 cases) and neighborhood controls matched for age and sex (817 cases) were titrated for antibodies to Epstein-Barr virus (EBV) by the indirect immunofluorescence antibody technique. High anti-EBV antibody titers (greater than or equal to 1:640) were noted in 55% in patients with NPC but only less than 31% were noted for the other 3 groups. The differences in the distributions of anti-EBV antibodies are statistically significant. The geometric mean levels of the antibody titers were 1:342 for the patients with NPC but less than 1:178 for the other 3 control groups. The relative risks shows that more than 40 times higher risk for those with equal to or higher than 1:640 antibody titers than those with lower than 1:40. The patients with NPC also show for higher ridit scales than the other 3 groups. The etiology of NPC was discussed with our findings."} {"id": "PMID:173500", "title": "[Peculiarities of primary hyperparathyroidism in childhood].", "content": "Following introductory remarks on the connected literature, a report is given on personal experience in the diagnosis and treatment of primary hyperparathyroidism (p.hpt) in a 14 years old girl. Clinical symptomatology and predominant form of organic manifestation as well as special biochemical diagnostic procedures of p.hpt in childhood are discussed. The necessity of longterm postoperative controls until complete regeneration of skeletal lesions and of adequate therapeutic Ca++-substitution is stressed.", "contents": "[Peculiarities of primary hyperparathyroidism in childhood]. Following introductory remarks on the connected literature, a report is given on personal experience in the diagnosis and treatment of primary hyperparathyroidism (p.hpt) in a 14 years old girl. Clinical symptomatology and predominant form of organic manifestation as well as special biochemical diagnostic procedures of p.hpt in childhood are discussed. The necessity of longterm postoperative controls until complete regeneration of skeletal lesions and of adequate therapeutic Ca++-substitution is stressed."} {"id": "PMID:173514", "title": "[Selective ACTH deficiency in two siblings (author's transl)].", "content": "In a previous report (Dtsch. med. Wschr. 97 [1972], 1943) the case of a 5-year-old boy had been described who, at autopsy, was found to have severe adrenocortical hypoplasia and absence of ACTH-producing R-cells of the anterior pituitary. On examining other members of his family, his 3 1/2-year old brother was found to have selective ACTH deficiency with secondary adrenocortical insufficiency. This is the first published report of two siblings with selective ACTH deficiency, presumably on a hereditary basis.", "contents": "[Selective ACTH deficiency in two siblings (author's transl)]. In a previous report (Dtsch. med. Wschr. 97 [1972], 1943) the case of a 5-year-old boy had been described who, at autopsy, was found to have severe adrenocortical hypoplasia and absence of ACTH-producing R-cells of the anterior pituitary. On examining other members of his family, his 3 1/2-year old brother was found to have selective ACTH deficiency with secondary adrenocortical insufficiency. This is the first published report of two siblings with selective ACTH deficiency, presumably on a hereditary basis."} {"id": "PMID:173517", "title": "[Etiology and prevention of recurring aphthous stomatitis].", "content": "New results concerning the etiology of recurrent aphthae are reported. According to own experiments of the authors, adenoviruses persisting in the epithelial cells of the oral mucosa may sensitize the aphthous patient. Adenovirus antigen was demonstrable in the oral mucosa cells in more than 50% of the patients and in the lymphocytes in approx. 1% of the patients. Lymphoblast transformation in the circulating lymphocytes could be demonstrated in vitro with heat-inactivated type 1 adenovirus, in 75% of the patients. This virus type has been isolated from 2 patients. K\u00f6bner's isomorphous phenomenon could be demonstrated in aphthous patients. The use of a disinfectant for mouth rinsing, the removal of foci as well as vitamin treatment are recommended for preventing recurrent aphthae.", "contents": "[Etiology and prevention of recurring aphthous stomatitis]. New results concerning the etiology of recurrent aphthae are reported. According to own experiments of the authors, adenoviruses persisting in the epithelial cells of the oral mucosa may sensitize the aphthous patient. Adenovirus antigen was demonstrable in the oral mucosa cells in more than 50% of the patients and in the lymphocytes in approx. 1% of the patients. Lymphoblast transformation in the circulating lymphocytes could be demonstrated in vitro with heat-inactivated type 1 adenovirus, in 75% of the patients. This virus type has been isolated from 2 patients. K\u00f6bner's isomorphous phenomenon could be demonstrated in aphthous patients. The use of a disinfectant for mouth rinsing, the removal of foci as well as vitamin treatment are recommended for preventing recurrent aphthae."} {"id": "PMID:173518", "title": "[Extension implantations as an aid in defect-restoring prosthodontics].", "content": "Because of a lack of denture retention, great difficulties are often encountered in edentulous patients who require prosthetic treatment of defects in the maxillo-facial region. The use of enossal implants may enable temporary rehabilitation with regard to mastication and speech. The possible range of indication is considerably limited in cases of extensive defects of the alveolar process, advanced atrophy and by radiological therapy of malignant tumors. The duration of therapeutic success is contingent upon most accurate implantation techniques and prosthetic treatment as well as the patient's oral hygiene.", "contents": "[Extension implantations as an aid in defect-restoring prosthodontics]. Because of a lack of denture retention, great difficulties are often encountered in edentulous patients who require prosthetic treatment of defects in the maxillo-facial region. The use of enossal implants may enable temporary rehabilitation with regard to mastication and speech. The possible range of indication is considerably limited in cases of extensive defects of the alveolar process, advanced atrophy and by radiological therapy of malignant tumors. The duration of therapeutic success is contingent upon most accurate implantation techniques and prosthetic treatment as well as the patient's oral hygiene."} {"id": "PMID:173521", "title": "Characterization of the androgen receptor in the anterior pituitary of the rat.", "content": "The specific androgen receptors for testosterone (T) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the anterior pituitary of rats have been further characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fraction in vivo and in vitro, we were able to demonstrate androgen-protein complexes moving with an electrophoretic mobility (Rf) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. This method was used for quantitative measurements of pituitary androgen receptors, allowing multiple samples to be run simultaneously with little or no non-specific binding. There was no measurable dissociation of the androgen-receptor complexes during electrophoresis. When radioactive testosterone (1 nM) was added to pituitary cytosol fractions in vitro, there was an increase in the binding up to 4 hours of incubation at 0 C and little or no increase between 4 and 24 hours. All the binding studies therefore were done by incubation overnight at 0 C. When cytosol fractions were incubated with increasing concentrations of radioactive testosterone, a typical saturation curve was found. Scatchard plot analysis showed a binding capacity of 12.0 femtomoles/mg protein and the equilibrium constant of dissociation was estimated to be 3.4 +/- 0.7 (SD) X 10(-10)M. Like other androgen-receptor complexes, the testosterone-receptor complex in the anterior pituitary gland had an extremely slow rate of dissociation at 0 C (t1/2 greater than 4 days). The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for [3H] testosterone binding. T and DHT caused the same inhibition of [3H]T to the receptors. However, since metabolism, of DHT to 5alpha-androstane-3alpha,17beta-diol occurred even at 0 C, the affinity of DHT for the receptor is probably somewhat underestimated. Cyproterone acetate had approximately half the affinity for the receptor compared with T, whereas lower affinities were found for progesterone and 17beta-estradiol. Cortisol did not appear to have any affinity for the receptors. Isoelectric focusing in polyacrylamide gels showed a peak of bound radioactivity with an isoelectric point of 5.8. Thus, the characteristics of the cytoplasmic androgen receptors of the anterior pituitary gland are very similar to those of the androgen receptors described in the ventral prostate, epididymis, and testis.", "contents": "Characterization of the androgen receptor in the anterior pituitary of the rat. The specific androgen receptors for testosterone (T) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the anterior pituitary of rats have been further characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fraction in vivo and in vitro, we were able to demonstrate androgen-protein complexes moving with an electrophoretic mobility (Rf) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. This method was used for quantitative measurements of pituitary androgen receptors, allowing multiple samples to be run simultaneously with little or no non-specific binding. There was no measurable dissociation of the androgen-receptor complexes during electrophoresis. When radioactive testosterone (1 nM) was added to pituitary cytosol fractions in vitro, there was an increase in the binding up to 4 hours of incubation at 0 C and little or no increase between 4 and 24 hours. All the binding studies therefore were done by incubation overnight at 0 C. When cytosol fractions were incubated with increasing concentrations of radioactive testosterone, a typical saturation curve was found. Scatchard plot analysis showed a binding capacity of 12.0 femtomoles/mg protein and the equilibrium constant of dissociation was estimated to be 3.4 +/- 0.7 (SD) X 10(-10)M. Like other androgen-receptor complexes, the testosterone-receptor complex in the anterior pituitary gland had an extremely slow rate of dissociation at 0 C (t1/2 greater than 4 days). The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for [3H] testosterone binding. T and DHT caused the same inhibition of [3H]T to the receptors. However, since metabolism, of DHT to 5alpha-androstane-3alpha,17beta-diol occurred even at 0 C, the affinity of DHT for the receptor is probably somewhat underestimated. Cyproterone acetate had approximately half the affinity for the receptor compared with T, whereas lower affinities were found for progesterone and 17beta-estradiol. Cortisol did not appear to have any affinity for the receptors. Isoelectric focusing in polyacrylamide gels showed a peak of bound radioactivity with an isoelectric point of 5.8. Thus, the characteristics of the cytoplasmic androgen receptors of the anterior pituitary gland are very similar to those of the androgen receptors described in the ventral prostate, epididymis, and testis."} {"id": "PMID:173522", "title": "Cytoplasmic and nuclear progesterone receptors in the guinea pig uterus.", "content": "Although progesterone receptors have been studied in the uterine cytoplasm of many species, relatively little was known about the nuclear content of these binding proteins. In the present study, a nuclear progesterone receptor was deteced in the guinea pig uterus. The binding of progesterone to the nuclear receptor was hormone and tissue specific. Furthermore, the nuclear localization of the progesterone receptor complex in the uterus was both time and temperature dependent. Since the nuclear receptor was extracted in high salt buffer, the effects of KCl on several physical properties of the cytoplasmic and nuclear binders were studied. In the presence of high salt, cytosol and nuclear receptors were virtually indistinguishable. These proteins were clearly distinguished upon removal of the KCl by rapid dialysis: the nuclear receptor had a slower sedimentation rate, a faster rate of dissociation and a higher binding affinity than did the cytosol receptor for progesterone. We conclude that the cytosol and nuclear receptors for progesterone in the guinea pig uterus are distinct macromolecules. These observations are consistent with the postulate that the cytoplasmic receptor is a precursor of that in the nucleus.", "contents": "Cytoplasmic and nuclear progesterone receptors in the guinea pig uterus. Although progesterone receptors have been studied in the uterine cytoplasm of many species, relatively little was known about the nuclear content of these binding proteins. In the present study, a nuclear progesterone receptor was deteced in the guinea pig uterus. The binding of progesterone to the nuclear receptor was hormone and tissue specific. Furthermore, the nuclear localization of the progesterone receptor complex in the uterus was both time and temperature dependent. Since the nuclear receptor was extracted in high salt buffer, the effects of KCl on several physical properties of the cytoplasmic and nuclear binders were studied. In the presence of high salt, cytosol and nuclear receptors were virtually indistinguishable. These proteins were clearly distinguished upon removal of the KCl by rapid dialysis: the nuclear receptor had a slower sedimentation rate, a faster rate of dissociation and a higher binding affinity than did the cytosol receptor for progesterone. We conclude that the cytosol and nuclear receptors for progesterone in the guinea pig uterus are distinct macromolecules. These observations are consistent with the postulate that the cytoplasmic receptor is a precursor of that in the nucleus."} {"id": "PMID:173523", "title": "Effects of hypophysectomy, ovariectomy, and cycloheximide on specific binding sites for lactogenic hormones in rat liver.", "content": "We have previously shown that specific binding sites for lactogenic hormones are present at much greater levels in the liver membranes of female than of male rats. In the present studies [125I]iodo-hGH was used to study binding sites specific for lactogenic hormones in liver membranes. In male rats, a single injection of 2 mg estradiol valerate induced these binding sites. The induction was maximal by 9-12 days and was dose-dependent. Ovariectomy significantly reduced the specific binding of [125I]iodo-hGH from 9.7 +/- 0.7% in shamoperated to 6.9 +/- 0.3% in experimental rats (P less than 0.01) without a change in affinity. Fluctuations in specific binding of [125I]iodo-hGH were observed at different stages of the estrous cycle. Binding at estrus and diestrus I was significantly greater than at diestrus II and proestrus (P less than 0.05). The disappearance of binding sites following hypophysectomy was rapid, declining from 13.2 +/- 1.2% in intact rats to 6.0 +/- 0.8% and 2.2 +/- 0.4% 14 and 48 h, respectively, after surgery. In contrast, binding of insulin was slightly increased after hypophysectomy. Anti-estrogens (clomiphene, ICI 46,474, and nafoxidine) prevented the induction of binding sites in male rats given estradiol (E2). A single injection of 200 mug cycloheximide 11 days after an injection of 2 mg E2-valerate reduced binding by more than 90% in 3 h with a return to control levels by 48 h. The maximal decline in insulin binding was 54% during this entire period. These studies suggest that endogenous estrogen plays a role in regulating hepatic binding sites for lactogenic hormones. The level of these binding sites is critically dependent on the presence of an intact pituitary. The possible rapid turnover of these sites suggests that regulatory influences at the tissue level may have an important role in modulating hormone action.", "contents": "Effects of hypophysectomy, ovariectomy, and cycloheximide on specific binding sites for lactogenic hormones in rat liver. We have previously shown that specific binding sites for lactogenic hormones are present at much greater levels in the liver membranes of female than of male rats. In the present studies [125I]iodo-hGH was used to study binding sites specific for lactogenic hormones in liver membranes. In male rats, a single injection of 2 mg estradiol valerate induced these binding sites. The induction was maximal by 9-12 days and was dose-dependent. Ovariectomy significantly reduced the specific binding of [125I]iodo-hGH from 9.7 +/- 0.7% in shamoperated to 6.9 +/- 0.3% in experimental rats (P less than 0.01) without a change in affinity. Fluctuations in specific binding of [125I]iodo-hGH were observed at different stages of the estrous cycle. Binding at estrus and diestrus I was significantly greater than at diestrus II and proestrus (P less than 0.05). The disappearance of binding sites following hypophysectomy was rapid, declining from 13.2 +/- 1.2% in intact rats to 6.0 +/- 0.8% and 2.2 +/- 0.4% 14 and 48 h, respectively, after surgery. In contrast, binding of insulin was slightly increased after hypophysectomy. Anti-estrogens (clomiphene, ICI 46,474, and nafoxidine) prevented the induction of binding sites in male rats given estradiol (E2). A single injection of 200 mug cycloheximide 11 days after an injection of 2 mg E2-valerate reduced binding by more than 90% in 3 h with a return to control levels by 48 h. The maximal decline in insulin binding was 54% during this entire period. These studies suggest that endogenous estrogen plays a role in regulating hepatic binding sites for lactogenic hormones. The level of these binding sites is critically dependent on the presence of an intact pituitary. The possible rapid turnover of these sites suggests that regulatory influences at the tissue level may have an important role in modulating hormone action."} {"id": "PMID:173524", "title": "Effect of intrathecal injection of melanotropic-lipolytic peptides on the concentration of 3',5' cyclic adenosine monophosphate in cerebrospinal fluid.", "content": "Rabbits were anesthetized with urethane, and the concentration of 3',5' cyclic adenosine monophosphate (cAMP) in cerebrospinal fluid (CSF) was measured before and after injection into the cisterna magna of the following biologically active peptides and amines; adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone (beta-MSH), choroid plexus peptide IIF, arginine vasopressin, oxytocin, glucagon, epinephrine, serotonin, histamine, and acetylcholine. Only epinephrine and the lipolytic-melanotropic peptides ACTH, beta-MSH, and IIF influenced cAMP. Five to 500 mug ACTH caused a 3 to 10X increase in cAMP within 30 min; the concentration of nucleotide returned to baseline within 60-90 min after 5 or 50 mug, and remained elevated for at least 120 min after 500 mug. Effects of the same magnitude and tempo as those caused by 5 to 500 mug ACTH were produced by .1 to 10 mug beta-MSH and 5 to 500 mug IIF. Epinephrine at doses of 5 to 500 mug caused rises in cAMP of similar degree as the same dose of ACTH or peptide IIF, but the peak value was not reached until 60 to 90 min after injection.", "contents": "Effect of intrathecal injection of melanotropic-lipolytic peptides on the concentration of 3',5' cyclic adenosine monophosphate in cerebrospinal fluid. Rabbits were anesthetized with urethane, and the concentration of 3',5' cyclic adenosine monophosphate (cAMP) in cerebrospinal fluid (CSF) was measured before and after injection into the cisterna magna of the following biologically active peptides and amines; adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone (beta-MSH), choroid plexus peptide IIF, arginine vasopressin, oxytocin, glucagon, epinephrine, serotonin, histamine, and acetylcholine. Only epinephrine and the lipolytic-melanotropic peptides ACTH, beta-MSH, and IIF influenced cAMP. Five to 500 mug ACTH caused a 3 to 10X increase in cAMP within 30 min; the concentration of nucleotide returned to baseline within 60-90 min after 5 or 50 mug, and remained elevated for at least 120 min after 500 mug. Effects of the same magnitude and tempo as those caused by 5 to 500 mug ACTH were produced by .1 to 10 mug beta-MSH and 5 to 500 mug IIF. Epinephrine at doses of 5 to 500 mug caused rises in cAMP of similar degree as the same dose of ACTH or peptide IIF, but the peak value was not reached until 60 to 90 min after injection."} {"id": "PMID:173525", "title": "The effect of elevated doses of thyrotropin on mouse thyroid.", "content": "In the course of validating the McKenzie assay it was found that large doses of bovine or rat TSH have a retarding effect on hormonal secretion from the thyroid. TSH in doses less than 10 mU had a maximal effect on thyroidal secretion at about 2-3 h after administration. Doses of TSH in excess of 10 mU caused the peak of secretion to appear at about 9-10 h and caused, as well, a decreased thyroidal iodine release at earlier times. This effect was not due to changes in the pattern of iodocompounds secreted by the thyroid or to a change in the clearance of the blood [125I] thyroxine. An estimate of the integrated secretion with time was linear with log dose up to 100 mU TSH. This pattern of response to TSH is also seen when colloid droplet formation is the parameter studied. cAMP accumulation shows a different pattern of response to TSH. Control levels of cAMP were 1-2 pmoles/mg thyroid. Doses of TSH smaller than 5 mU caused no significant increase in cAMP. With a further increase in TSH up to 200 mU per mouse, cAMP levels increased linearly with the log of TSH and reached 400 pmoles/mg thyroid. Theophylline administered together with large doses of TSH increased the level of the thyroidal cAMP and further decreased the release of iodocompounds at 2 h. These results indicate that there may be an intrathyroidal mechanism which prevents a surge of secretion of thyroid hormones with acute changes in blood TSH levels. The mechanism sensitive to excess TSH is probably associated with steps in thyroidal activation between the accumulation of cAMP and colloid droplet formation.", "contents": "The effect of elevated doses of thyrotropin on mouse thyroid. In the course of validating the McKenzie assay it was found that large doses of bovine or rat TSH have a retarding effect on hormonal secretion from the thyroid. TSH in doses less than 10 mU had a maximal effect on thyroidal secretion at about 2-3 h after administration. Doses of TSH in excess of 10 mU caused the peak of secretion to appear at about 9-10 h and caused, as well, a decreased thyroidal iodine release at earlier times. This effect was not due to changes in the pattern of iodocompounds secreted by the thyroid or to a change in the clearance of the blood [125I] thyroxine. An estimate of the integrated secretion with time was linear with log dose up to 100 mU TSH. This pattern of response to TSH is also seen when colloid droplet formation is the parameter studied. cAMP accumulation shows a different pattern of response to TSH. Control levels of cAMP were 1-2 pmoles/mg thyroid. Doses of TSH smaller than 5 mU caused no significant increase in cAMP. With a further increase in TSH up to 200 mU per mouse, cAMP levels increased linearly with the log of TSH and reached 400 pmoles/mg thyroid. Theophylline administered together with large doses of TSH increased the level of the thyroidal cAMP and further decreased the release of iodocompounds at 2 h. These results indicate that there may be an intrathyroidal mechanism which prevents a surge of secretion of thyroid hormones with acute changes in blood TSH levels. The mechanism sensitive to excess TSH is probably associated with steps in thyroidal activation between the accumulation of cAMP and colloid droplet formation."} {"id": "PMID:173526", "title": "Ovarian cyclic adenosine monophosphate-dependent protein kinase activity: ontogeny and effect of gonadotropins.", "content": "The ontogeny of ovarian cyclic AMP-binding and protein kinase activities during the postnatal development of the rat, as well as the effect of LH and FSH administration on ovarian cyclic AMP-binding and protein kinase activities in 5-day-old and in hypophysectomized rats was examined. Ovaries of 4 to 8-day-old rats possessed little or no measureable cyclic AMP-binding and protein kinase activities. Subsequent postnatal development occurred in three distinct phases. During the first phase, ovarian cyclic AMP-binding and protein kinase activities increased progressively from age 8 days to age 23 days, when adult levels were observed. Protein kinase activity declined markedly during the second postnatal developmental phase from days 24 to 26, lost its cyclic AMP-dependency, and became refractory to stimulation by cyclic AMP. Studies employing a heat-stable protein kinase inhibitor protein isolated from rabbit skeletal muscle suggest that ovarian protein kinase activity during the refractory period was largely of the cyclic AMP-independent variety. During the third postnatal phase, comprising days 30 to 40, ovarian cyclic AMP-binding and protein kinase activities increased to levels seen in sexually mature rats. Protein kinase cyclic AMP-dependency which was lost during the refractory second postnatal period was fully restored during the third phase. Administration of FSH or LH led to a marked increase of ovarian cyclic AMP-binding and protein kinase activities in 5-day-old rats. Hypophysectomy of 20-day-old rats caused a significant reduction of the cyclic AMP-binding and protein kinase activities in a 27,000 X g supernatant fraction, as well as in the mitochondrial, microsomal, and 105,000 X g supernatant fraction. The decreased cyclic AMP-binding and protein kinase activities of these fractions could be partially restored by FSH or LH treatment of the hypophysectomized rats. The results indicate that ovarian cyclic AMP-binding and protein kinase activities, as well as the ability of ovarian protein kinase to respond to cyclic AMP are gradually acquired after the first postnatal week. The postnatal development of ovarian protein kinase and cyclic AMP-binding activities presumably involves the participation of FSH and LH, although the precise mechanism of LH and FSH action remains to be established.", "contents": "Ovarian cyclic adenosine monophosphate-dependent protein kinase activity: ontogeny and effect of gonadotropins. The ontogeny of ovarian cyclic AMP-binding and protein kinase activities during the postnatal development of the rat, as well as the effect of LH and FSH administration on ovarian cyclic AMP-binding and protein kinase activities in 5-day-old and in hypophysectomized rats was examined. Ovaries of 4 to 8-day-old rats possessed little or no measureable cyclic AMP-binding and protein kinase activities. Subsequent postnatal development occurred in three distinct phases. During the first phase, ovarian cyclic AMP-binding and protein kinase activities increased progressively from age 8 days to age 23 days, when adult levels were observed. Protein kinase activity declined markedly during the second postnatal developmental phase from days 24 to 26, lost its cyclic AMP-dependency, and became refractory to stimulation by cyclic AMP. Studies employing a heat-stable protein kinase inhibitor protein isolated from rabbit skeletal muscle suggest that ovarian protein kinase activity during the refractory period was largely of the cyclic AMP-independent variety. During the third postnatal phase, comprising days 30 to 40, ovarian cyclic AMP-binding and protein kinase activities increased to levels seen in sexually mature rats. Protein kinase cyclic AMP-dependency which was lost during the refractory second postnatal period was fully restored during the third phase. Administration of FSH or LH led to a marked increase of ovarian cyclic AMP-binding and protein kinase activities in 5-day-old rats. Hypophysectomy of 20-day-old rats caused a significant reduction of the cyclic AMP-binding and protein kinase activities in a 27,000 X g supernatant fraction, as well as in the mitochondrial, microsomal, and 105,000 X g supernatant fraction. The decreased cyclic AMP-binding and protein kinase activities of these fractions could be partially restored by FSH or LH treatment of the hypophysectomized rats. The results indicate that ovarian cyclic AMP-binding and protein kinase activities, as well as the ability of ovarian protein kinase to respond to cyclic AMP are gradually acquired after the first postnatal week. The postnatal development of ovarian protein kinase and cyclic AMP-binding activities presumably involves the participation of FSH and LH, although the precise mechanism of LH and FSH action remains to be established."} {"id": "PMID:173527", "title": "Interaction of spironolactone and digitalis with the 5 alpha-dihydrotestosterone (DHT) receptor of rat ventral prostate.", "content": "The aldosterone antagonist, spironolactone, has been shown to block the effects of exogenously administered androgen in rat. This suggests that interaction of the drug with androgen at the target tissues may occur. In this paper we have studied the possible interaction of spironolactone with the 5alpha-dihydrotestosterone (DHT)1 receptor of rat ventral prostate. The competitive receptor assay used involves precipitation of the 105,000 X g supernatant of the homogenized tissue with protamine sulfate, removal of the unprecipitated cytosol, and incubation of the precipitate in the presence of the appropriate [3H]DHT steroid solution at 0 C for 18 hours. Using this method the Kd (dissociation constant) for DHT in the rat prostate was in the range of 1.9-4.0 X 10(-9)M and the binding capacity was 0.21 pmol/mg protein. Spironolactone was found to interfere with the binding of DHT to the precipitated cytosol and displayed an estimated Kd of 1.3-4.6 X 10(-8)M. Several digitalis preparations were similarly studied. Digitoxin and digitoxigenin also interfered with the binding of [3H]DHT and had an estimated Kd of 0.8-3.6 X 10(-8)M. Digoxin interacted less strongly and its estimated Kd was 10(-6)M. We believe these results suggest an interaction of spironolactone and digitalis with the DHT receptor and may help explain some of their antiandrogenic actions in the rat and in man.", "contents": "Interaction of spironolactone and digitalis with the 5 alpha-dihydrotestosterone (DHT) receptor of rat ventral prostate. The aldosterone antagonist, spironolactone, has been shown to block the effects of exogenously administered androgen in rat. This suggests that interaction of the drug with androgen at the target tissues may occur. In this paper we have studied the possible interaction of spironolactone with the 5alpha-dihydrotestosterone (DHT)1 receptor of rat ventral prostate. The competitive receptor assay used involves precipitation of the 105,000 X g supernatant of the homogenized tissue with protamine sulfate, removal of the unprecipitated cytosol, and incubation of the precipitate in the presence of the appropriate [3H]DHT steroid solution at 0 C for 18 hours. Using this method the Kd (dissociation constant) for DHT in the rat prostate was in the range of 1.9-4.0 X 10(-9)M and the binding capacity was 0.21 pmol/mg protein. Spironolactone was found to interfere with the binding of DHT to the precipitated cytosol and displayed an estimated Kd of 1.3-4.6 X 10(-8)M. Several digitalis preparations were similarly studied. Digitoxin and digitoxigenin also interfered with the binding of [3H]DHT and had an estimated Kd of 0.8-3.6 X 10(-8)M. Digoxin interacted less strongly and its estimated Kd was 10(-6)M. We believe these results suggest an interaction of spironolactone and digitalis with the DHT receptor and may help explain some of their antiandrogenic actions in the rat and in man."} {"id": "PMID:173528", "title": "Diethylstilbestrol-elicited accumulation of cyclic AMP in incubated rat hypothalamus.", "content": "Diethylstilbestrol (DES) and 17beta-estradiol elicit significant increases in levels of endogenous and [14C]cyclic AMP in [14C]adeninelabeled hypothalami from immature female rats, but only after incubation of the hypothalami with these estrogenic agents for 40-50 min. Estriol has no effect. The 2-fold accumulation of cyclic AMP elicited by low concentrations (20 muM) of DES appears dependent on catecholamine-related mechanisms, since it is prevented by either alpha- or beta-adrenergic antagonists. Higher concentrations (100 muM) of DES elicit a 3-fold accumulation of [14C]cyclic AMP which is only partially blocked by adrenergic antagonists, haloperidol, or the adenosine antagonist, theophylline. These phenomena appear to be specific for the hypothalamus since incubation of cerebral cortical slabs with estrogens resulted in no significant increases in the levels of cyclic AMP. The slow time course in whole hypothalami and the complete lack of effects of low concentrations of estrogenic agents in chopped hypothalami suggest an indirect mechanism of action. Interaction of estrogens with receptors in cell bodies may result, after a latent period of 40-50 min, in enhanced release of catecholamines from distal synaptic terminals and in stimulation of catecholamine-sensitive adenylate cyclases at post-synaptic sites.", "contents": "Diethylstilbestrol-elicited accumulation of cyclic AMP in incubated rat hypothalamus. Diethylstilbestrol (DES) and 17beta-estradiol elicit significant increases in levels of endogenous and [14C]cyclic AMP in [14C]adeninelabeled hypothalami from immature female rats, but only after incubation of the hypothalami with these estrogenic agents for 40-50 min. Estriol has no effect. The 2-fold accumulation of cyclic AMP elicited by low concentrations (20 muM) of DES appears dependent on catecholamine-related mechanisms, since it is prevented by either alpha- or beta-adrenergic antagonists. Higher concentrations (100 muM) of DES elicit a 3-fold accumulation of [14C]cyclic AMP which is only partially blocked by adrenergic antagonists, haloperidol, or the adenosine antagonist, theophylline. These phenomena appear to be specific for the hypothalamus since incubation of cerebral cortical slabs with estrogens resulted in no significant increases in the levels of cyclic AMP. The slow time course in whole hypothalami and the complete lack of effects of low concentrations of estrogenic agents in chopped hypothalami suggest an indirect mechanism of action. Interaction of estrogens with receptors in cell bodies may result, after a latent period of 40-50 min, in enhanced release of catecholamines from distal synaptic terminals and in stimulation of catecholamine-sensitive adenylate cyclases at post-synaptic sites."} {"id": "PMID:173529", "title": "Aldosterone production by isolated adrenal glomerulosa cells: stimulation by physiological concentrations of angiotensin II.", "content": "The production of aldosterone by isolated canine zona glomerulosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. Adrenal cell suspensions were prepared by collagenase digestion and physical dispersion of the capsular layer of the dog adrenal cortex, and aldosterone production was determined by direct radioimmunoassay of cell incubation media. The isolated dog adrenal cells were highly responsive to angiotensin II, with aldosterone production significantly stimulated by concentrations of the octapeptide as low as 10(-11)M. Thus, the steroidogenic response of zona glomerulosa cells was consistently observed at peptide concentrations within the physiological range of angiotensin II in dog plasma, i.e., 2.0-5.0 X 5.0 X 10(-11)M. The maximum aldosterone response of 3-8 times the basal level of steroid production was induced by 3 X 10(-10)M angiotensin II, and a decrease in aldosterone production occurred at peptide concentrations above 10(-9)M. The aldosterone response of isolated adrenal cells to ACTH was consistently less sensitive than their response to angiotensin II, by a factor of 10-20 fold. Aldosterone production was significantly increased by 10(-10)M ACTH, and reached a maximum at 10(-8)M ACTH. By contrast with angiotensin II, ACTH usually evoked a higher maximal level of aldosterone production, and did not produce a decline in steroidogenesis at peptide concentrations above the level which caused maximum stimulation of aldosterone formation. Changes in the potassium concentration of cell incubation media were also accompanied by marked effects upon aldosterone synthesis which was abolished in the absence of potassium and became detectable in the presence of 0.5 mM K+. After remaining constant between 2.5 and 4.0 mM K+, aldosterone production rose sharply above 4.5 mM K+ and reached a maximum at 8 mM K+. These observations provide direct evidence that aldosterone production by zona glomerulosa cells is influenced by changes in angiotensin II levels within the normal plasma range.", "contents": "Aldosterone production by isolated adrenal glomerulosa cells: stimulation by physiological concentrations of angiotensin II. The production of aldosterone by isolated canine zona glomerulosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. Adrenal cell suspensions were prepared by collagenase digestion and physical dispersion of the capsular layer of the dog adrenal cortex, and aldosterone production was determined by direct radioimmunoassay of cell incubation media. The isolated dog adrenal cells were highly responsive to angiotensin II, with aldosterone production significantly stimulated by concentrations of the octapeptide as low as 10(-11)M. Thus, the steroidogenic response of zona glomerulosa cells was consistently observed at peptide concentrations within the physiological range of angiotensin II in dog plasma, i.e., 2.0-5.0 X 5.0 X 10(-11)M. The maximum aldosterone response of 3-8 times the basal level of steroid production was induced by 3 X 10(-10)M angiotensin II, and a decrease in aldosterone production occurred at peptide concentrations above 10(-9)M. The aldosterone response of isolated adrenal cells to ACTH was consistently less sensitive than their response to angiotensin II, by a factor of 10-20 fold. Aldosterone production was significantly increased by 10(-10)M ACTH, and reached a maximum at 10(-8)M ACTH. By contrast with angiotensin II, ACTH usually evoked a higher maximal level of aldosterone production, and did not produce a decline in steroidogenesis at peptide concentrations above the level which caused maximum stimulation of aldosterone formation. Changes in the potassium concentration of cell incubation media were also accompanied by marked effects upon aldosterone synthesis which was abolished in the absence of potassium and became detectable in the presence of 0.5 mM K+. After remaining constant between 2.5 and 4.0 mM K+, aldosterone production rose sharply above 4.5 mM K+ and reached a maximum at 8 mM K+. These observations provide direct evidence that aldosterone production by zona glomerulosa cells is influenced by changes in angiotensin II levels within the normal plasma range."} {"id": "PMID:173530", "title": "Effect of ACTH, alpha-MSH, and beta-Lipotropin on calcium and phosphorus metabolism in the rabbit.", "content": "Studies were undertaken to investigate the effects of synthetic 1-24 adrenocorticotropin (ACTH), bovine alpha melanocyte-stimulating hormone (alpha-MSH), and ovine beta lipotropin (beta-LPH) on plasma calcium and phosphate in rabbits. Equimolar concentrations of these hormones were infused intravenously in intact and thyroidectomized animals. In addition, ACTH was similarly administered to adrenalectomized rabbits. ACTH, alpha-MSH, and beta-LPH all lowered plasma calcium and raised plasma phosphate. These changes were not prevented by prior thyroidectomy. ACTH was equally effective in inducing hypocalcemia and hyperphosphatemia in the absence of the adrenal glands, while adrenalectomy alone raised plasma calcium. From these findings we have concluded that 1) ACTH, alpha-MSH, and betaLPH affect phosphate as well as calcium metabolism; 2) these hormones do not act by releasing calcitonin; and 3) ACTH exerts its hypocalcemic-hyperphosphatemic effect, at least in part, independently of its trophic action on the adrenal glands.", "contents": "Effect of ACTH, alpha-MSH, and beta-Lipotropin on calcium and phosphorus metabolism in the rabbit. Studies were undertaken to investigate the effects of synthetic 1-24 adrenocorticotropin (ACTH), bovine alpha melanocyte-stimulating hormone (alpha-MSH), and ovine beta lipotropin (beta-LPH) on plasma calcium and phosphate in rabbits. Equimolar concentrations of these hormones were infused intravenously in intact and thyroidectomized animals. In addition, ACTH was similarly administered to adrenalectomized rabbits. ACTH, alpha-MSH, and beta-LPH all lowered plasma calcium and raised plasma phosphate. These changes were not prevented by prior thyroidectomy. ACTH was equally effective in inducing hypocalcemia and hyperphosphatemia in the absence of the adrenal glands, while adrenalectomy alone raised plasma calcium. From these findings we have concluded that 1) ACTH, alpha-MSH, and betaLPH affect phosphate as well as calcium metabolism; 2) these hormones do not act by releasing calcitonin; and 3) ACTH exerts its hypocalcemic-hyperphosphatemic effect, at least in part, independently of its trophic action on the adrenal glands."} {"id": "PMID:173531", "title": "The covalent structure of collagen. The amino-acid sequence of alpha2-CB4 from calf-skin collagen.", "content": "Sequencing of chymotrypsin, trypsin, collagenase- and hydroxylamine-derived peptides, using the automated Edman degradation procedure, yielded the complete amino acid sequence of alpha2-CB4 from calf skin collagen (321 residues). Together with the data from earlier work, an uninterrupted sequence in the helical region of the alpha2-chain from residues 1-393 is now known. Glycine is found in every third position of the peptide. Hydroxylation of proline and lysine occurs only in the Y-position of the triplet Gly-X-Y and is not complete in every position. Some residues, such as glutamic acid, leucine, phenylalanine and arginine, are distributed non-randomly between the X and Y-positions and this non-random distribution is different in the alpha1 and alpha2-chains. Comparison of the N-terminal 393 residues from the helical region of the alpha1 and alpha2-chains revealed a nearly identical distribution of charged polar residues arginine, lysine, glutamic and aspartic acids. The distribution of the triplet Gly-Pro-Hyp is simialr in both chains. The remaining residues in the alpha2-chain exhibit a high degree of substitutions when compared with those in the alpha1-chain. Approximately one in every two residues in both the X and Y-positions are substituted.", "contents": "The covalent structure of collagen. The amino-acid sequence of alpha2-CB4 from calf-skin collagen. Sequencing of chymotrypsin, trypsin, collagenase- and hydroxylamine-derived peptides, using the automated Edman degradation procedure, yielded the complete amino acid sequence of alpha2-CB4 from calf skin collagen (321 residues). Together with the data from earlier work, an uninterrupted sequence in the helical region of the alpha2-chain from residues 1-393 is now known. Glycine is found in every third position of the peptide. Hydroxylation of proline and lysine occurs only in the Y-position of the triplet Gly-X-Y and is not complete in every position. Some residues, such as glutamic acid, leucine, phenylalanine and arginine, are distributed non-randomly between the X and Y-positions and this non-random distribution is different in the alpha1 and alpha2-chains. Comparison of the N-terminal 393 residues from the helical region of the alpha1 and alpha2-chains revealed a nearly identical distribution of charged polar residues arginine, lysine, glutamic and aspartic acids. The distribution of the triplet Gly-Pro-Hyp is simialr in both chains. The remaining residues in the alpha2-chain exhibit a high degree of substitutions when compared with those in the alpha1-chain. Approximately one in every two residues in both the X and Y-positions are substituted."} {"id": "PMID:173532", "title": "Investigations on the kinetic mechanism of octopine dehydrogenase. 2. Location of the rate-limiting step for enzyme turnover.", "content": "The kinetic mechanism of octopine dehydrogenase has been investigated by stopped-flow and isotope replacement techniques. When the enzyme is saturated by substrate and coenzyme, both for NADH oxidation and NAD+ reduction, the stationary phase is preceded by a rapid burst. Under these saturation conditions, furthermore, the stationary phase shows a secondary isotope effect when 4S-[4(2)H]NADH is substituted for NADH and when (on the other reaction end) D-[2H] octopine is substituted for D-octopine. The data are taken to indicate that the rate-limiting step for enzyme turnover is a step following a very fast chemical transformation of the reagents. However, when the substrate concentration is lowered below the corresponding Km value keeping the coenzyme concentration at saturating levels, the time course of the reaction shows no burst and the stationary phase has a larger isotope effect. This indicated that under those non-saturating conditions, the enzyme turnover has a larger contribution than the hydrogen-transfer step. Changing the coenzyme concentration alone has very little or no effect on the amplitude of the burst or on the isotope effect. These features are discussed in terms of the other known kinetic properties of the enzyme, and in terms of analogous studies reported in the literature for other dehydrogenases.", "contents": "Investigations on the kinetic mechanism of octopine dehydrogenase. 2. Location of the rate-limiting step for enzyme turnover. The kinetic mechanism of octopine dehydrogenase has been investigated by stopped-flow and isotope replacement techniques. When the enzyme is saturated by substrate and coenzyme, both for NADH oxidation and NAD+ reduction, the stationary phase is preceded by a rapid burst. Under these saturation conditions, furthermore, the stationary phase shows a secondary isotope effect when 4S-[4(2)H]NADH is substituted for NADH and when (on the other reaction end) D-[2H] octopine is substituted for D-octopine. The data are taken to indicate that the rate-limiting step for enzyme turnover is a step following a very fast chemical transformation of the reagents. However, when the substrate concentration is lowered below the corresponding Km value keeping the coenzyme concentration at saturating levels, the time course of the reaction shows no burst and the stationary phase has a larger isotope effect. This indicated that under those non-saturating conditions, the enzyme turnover has a larger contribution than the hydrogen-transfer step. Changing the coenzyme concentration alone has very little or no effect on the amplitude of the burst or on the isotope effect. These features are discussed in terms of the other known kinetic properties of the enzyme, and in terms of analogous studies reported in the literature for other dehydrogenases."} {"id": "PMID:173533", "title": "3-Deoxy-2-octulosonic acid 5-phosphate: a component of the endotoxin of Bordetella pertussis.", "content": "Upon hydrolysis with 2 N hydrochloric acid for 2 h, a 3-deoxy-octulosonic acid 5-phosphate was released from the endotoxin of Bordetella pertussis. The structure of the compound was established through chemical degradation. By periodate treatment of the intact endotoxin it was shown that positions 7 and 8 of the bound octulosonic acid phosphate were free, which, if present in a cyclic form, must be a pyranoside.", "contents": "3-Deoxy-2-octulosonic acid 5-phosphate: a component of the endotoxin of Bordetella pertussis. Upon hydrolysis with 2 N hydrochloric acid for 2 h, a 3-deoxy-octulosonic acid 5-phosphate was released from the endotoxin of Bordetella pertussis. The structure of the compound was established through chemical degradation. By periodate treatment of the intact endotoxin it was shown that positions 7 and 8 of the bound octulosonic acid phosphate were free, which, if present in a cyclic form, must be a pyranoside."} {"id": "PMID:173534", "title": "Electron paramagnetic resonance studies of cytochrome P-450 in plant microsomes.", "content": "The technique of electron paramagnetic resonnance spectrometry has been applied to the study of plant microsomal electron-transport components. Only tulip-bulb microsomes were found to give strong enough signals to allow detailed study. At 77 K in the oxidised state, signals were observed at g values of 2.40, 2.25 and 1.93, characteristic of cytochrome P-450 in the low-spin state, and also at g = 4.27, attributable to ferric iron in a rhombic environment. The signals at g = 2.40, 2.25 and 1.93 disappeared upon reduction with sodium dithionite. At 10 K in the oxidised state, signals at g = 8.3 and 3.3 appeared, and these were attributed to high-spin cytochrome P-450. At this temperature a further signal at g = 6, due to cytochrome P-420, was seen in aged tulip-bulb microsomes. Redox titration of both high-spin and low-spin cytochrome P-450 gave the same apparent midpoint potential of -315 +/- mV at pH 6.8 and 25 degrees C. The significance of this value is discussed. Addition of \"type I\" or \"type II\" ligands to oxidized cytochrome P-450 caused an increase and a decrease, respectively, in the ratio of the high-spin to the low-spin form. A second effect of aniline, a type II ligand of cytochrome P-450, was to remove the g = 6 signal, suggesting that it also interacts with cytochrome P-420. No iron-sulphur proteins similar to those found in some other cytochrome P-450 electron-transport chains could be detected in any of the microsomes analysed.", "contents": "Electron paramagnetic resonance studies of cytochrome P-450 in plant microsomes. The technique of electron paramagnetic resonnance spectrometry has been applied to the study of plant microsomal electron-transport components. Only tulip-bulb microsomes were found to give strong enough signals to allow detailed study. At 77 K in the oxidised state, signals were observed at g values of 2.40, 2.25 and 1.93, characteristic of cytochrome P-450 in the low-spin state, and also at g = 4.27, attributable to ferric iron in a rhombic environment. The signals at g = 2.40, 2.25 and 1.93 disappeared upon reduction with sodium dithionite. At 10 K in the oxidised state, signals at g = 8.3 and 3.3 appeared, and these were attributed to high-spin cytochrome P-450. At this temperature a further signal at g = 6, due to cytochrome P-420, was seen in aged tulip-bulb microsomes. Redox titration of both high-spin and low-spin cytochrome P-450 gave the same apparent midpoint potential of -315 +/- mV at pH 6.8 and 25 degrees C. The significance of this value is discussed. Addition of \"type I\" or \"type II\" ligands to oxidized cytochrome P-450 caused an increase and a decrease, respectively, in the ratio of the high-spin to the low-spin form. A second effect of aniline, a type II ligand of cytochrome P-450, was to remove the g = 6 signal, suggesting that it also interacts with cytochrome P-420. No iron-sulphur proteins similar to those found in some other cytochrome P-450 electron-transport chains could be detected in any of the microsomes analysed."} {"id": "PMID:173535", "title": "Temperature sensitivity of cyclic-adenosine-3':5'-monophosphate-binding proteins, activity of protein kinases and the regulation of cell growth.", "content": "A clone of neuroblastoma cells has been selected for its ability to survive and multiply at 40 degrees C. This temperature-resistant clone, like clones of neuroblastoma cells selected for resistance to dibutyryladenosine 3':5'-monophosphate (Bt2-Ado-3':5'-P) showed an increased tumorogenicity in animals and an increased saturation density at 37 degrees C. The Ado-3':5'-P-binding proteins and Ado-3':5'-P-dependent protein kinases from the temperature-resistant and non-resistant cells have been partially purified by chromatography on a DEAE-cellulose column. The Ado-3':5'-P-binding proteins from temperature-resistant cells were more sensitive to temperature than the binding proteins from non-resistant cells. After incubation of binding proteins from resistant cells at 37 degrees C, the specific activity of Ado-3':5'-P-binding to proteins was decreased about 50% and the apparent association constant (Ka) for Ado-3':5-p-binding was decreased from 7.4 X 10(7)M-1 to 4.4 x 10(7)M-1. There was no such decrease with binding proteins from non-resistant cells. A decrease in the activity of binding proteins from the temperature-resistant cells, but not of those from non-resistant cells, was also found when the proteins were stored at 2 degrees C. Treatment with 2-mercaptoethanol made binding proteins from the resistant cells less temperature-sensitive. In the absence of added Ado-3:5-P the protein kinase activity from the temperature-resistant cells was about 50% of the activity from non-resistant cells. Kinase activity was increased by addition of Ado-3:5-P and there was a greater increase with kinases from resistant cells. The maximum protein kinase activity was found in the presence of 10muM Ado-3':5'-P for the temperature-resistant cells and 0.1 muM Ado-3':5'-P for the non-resistant cells. The results indicate that the temperature sensitivity of Ado-3':5'-P-binding proteins, and the activity of protein kinase from cells selected for resistance to high temperature, are similar to those of cells selected for resistance to Bt2-Ado-3':5'-P. It is suggested that the temperature sensitivity of Ado-3':5'-P-binding proteins and the activity of Ado-3':5'-P-dependent protein kinases are involved in the regulation of malignancy and of cell growth at different temperatures.", "contents": "Temperature sensitivity of cyclic-adenosine-3':5'-monophosphate-binding proteins, activity of protein kinases and the regulation of cell growth. A clone of neuroblastoma cells has been selected for its ability to survive and multiply at 40 degrees C. This temperature-resistant clone, like clones of neuroblastoma cells selected for resistance to dibutyryladenosine 3':5'-monophosphate (Bt2-Ado-3':5'-P) showed an increased tumorogenicity in animals and an increased saturation density at 37 degrees C. The Ado-3':5'-P-binding proteins and Ado-3':5'-P-dependent protein kinases from the temperature-resistant and non-resistant cells have been partially purified by chromatography on a DEAE-cellulose column. The Ado-3':5'-P-binding proteins from temperature-resistant cells were more sensitive to temperature than the binding proteins from non-resistant cells. After incubation of binding proteins from resistant cells at 37 degrees C, the specific activity of Ado-3':5'-P-binding to proteins was decreased about 50% and the apparent association constant (Ka) for Ado-3':5-p-binding was decreased from 7.4 X 10(7)M-1 to 4.4 x 10(7)M-1. There was no such decrease with binding proteins from non-resistant cells. A decrease in the activity of binding proteins from the temperature-resistant cells, but not of those from non-resistant cells, was also found when the proteins were stored at 2 degrees C. Treatment with 2-mercaptoethanol made binding proteins from the resistant cells less temperature-sensitive. In the absence of added Ado-3:5-P the protein kinase activity from the temperature-resistant cells was about 50% of the activity from non-resistant cells. Kinase activity was increased by addition of Ado-3:5-P and there was a greater increase with kinases from resistant cells. The maximum protein kinase activity was found in the presence of 10muM Ado-3':5'-P for the temperature-resistant cells and 0.1 muM Ado-3':5'-P for the non-resistant cells. The results indicate that the temperature sensitivity of Ado-3':5'-P-binding proteins, and the activity of protein kinase from cells selected for resistance to high temperature, are similar to those of cells selected for resistance to Bt2-Ado-3':5'-P. It is suggested that the temperature sensitivity of Ado-3':5'-P-binding proteins and the activity of Ado-3':5'-P-dependent protein kinases are involved in the regulation of malignancy and of cell growth at different temperatures."} {"id": "PMID:173536", "title": "The pyruvate-dehydrogenase complex from Azotobacter vinelandii. 3. Stoichiometry and function of the individual components.", "content": "Labelling studies with N-ETHYLMALEIMIDE SHOW THAT EITHER IN THE PRESENCE OF Mg2+, thiamine pyrophosphate (TPP) and pyruvate or in the presence of NADH the overall activity of the pyruvate dehydrogenase complex from Azotobacter vinelandii is inhibited without much inhibition of the partial reactions. The complex undergoes a conformational change upon incubation with NADH. The inhibition by bromopyruvate is less specific. Specific incorporation of a fluorescent maleimide derivative was observed on the two transacetylase isoenzymes. Binding studies with a similar spin label analogue show that 3 molecules/FAD are incorporated by incubation of pyruvate, Mg2+ and TPP, whereas 2 molecules/FAD are incorporated via incubation with NADH. The spin label spectra support the idea that in the complex the active centres of the component enzymes are connected by rapid rotation of the lipoyl moiety. Three acetyl groups are incorporated in the complex by incubation with [2-14C]pyruvate. Time-dependent incorporation supports the view that the two transacetylase isoenzymes react in non-identical ways with the pyruvate dehydrogenase components of the complex. The results show that the complex contains 2 low-molecular-weight transacetylase molecules and 4 molecules of the high-molecular-weight isoenzyme. Mn2+-binding studies show that the complex binds 10 ions, with different affinities. 2 Mn2+ ions are bound with a 20-fold higher affinity than the remaining 8 Mn2+ ions. The latter 8 ions bind with equal affinities and are thought to reflect binding to the pyruvate dehydrogenase components of the complex. It is concluded that the complex contains 8 pyruvate dehydrogenase molecules, 4 high-molecular-weight transacetylase molecules, 2 low-molecular-weight transacetylase molecules and 1 dimeric (2-FAD-containing) symmetric molecule of lipoamide dehydrogenase. Evidence comes from pyruvate-dependent inactivation and labelling studies that the pyruvate dehydrogenase components contain either an - SH group or an S-S bridge which participates in the hydroxyethyl transfer to the transacetylase components.", "contents": "The pyruvate-dehydrogenase complex from Azotobacter vinelandii. 3. Stoichiometry and function of the individual components. Labelling studies with N-ETHYLMALEIMIDE SHOW THAT EITHER IN THE PRESENCE OF Mg2+, thiamine pyrophosphate (TPP) and pyruvate or in the presence of NADH the overall activity of the pyruvate dehydrogenase complex from Azotobacter vinelandii is inhibited without much inhibition of the partial reactions. The complex undergoes a conformational change upon incubation with NADH. The inhibition by bromopyruvate is less specific. Specific incorporation of a fluorescent maleimide derivative was observed on the two transacetylase isoenzymes. Binding studies with a similar spin label analogue show that 3 molecules/FAD are incorporated by incubation of pyruvate, Mg2+ and TPP, whereas 2 molecules/FAD are incorporated via incubation with NADH. The spin label spectra support the idea that in the complex the active centres of the component enzymes are connected by rapid rotation of the lipoyl moiety. Three acetyl groups are incorporated in the complex by incubation with [2-14C]pyruvate. Time-dependent incorporation supports the view that the two transacetylase isoenzymes react in non-identical ways with the pyruvate dehydrogenase components of the complex. The results show that the complex contains 2 low-molecular-weight transacetylase molecules and 4 molecules of the high-molecular-weight isoenzyme. Mn2+-binding studies show that the complex binds 10 ions, with different affinities. 2 Mn2+ ions are bound with a 20-fold higher affinity than the remaining 8 Mn2+ ions. The latter 8 ions bind with equal affinities and are thought to reflect binding to the pyruvate dehydrogenase components of the complex. It is concluded that the complex contains 8 pyruvate dehydrogenase molecules, 4 high-molecular-weight transacetylase molecules, 2 low-molecular-weight transacetylase molecules and 1 dimeric (2-FAD-containing) symmetric molecule of lipoamide dehydrogenase. Evidence comes from pyruvate-dependent inactivation and labelling studies that the pyruvate dehydrogenase components contain either an - SH group or an S-S bridge which participates in the hydroxyethyl transfer to the transacetylase components."} {"id": "PMID:173537", "title": "The consequences of lipid peroxidation in isolated hepatocytes.", "content": "Lipid peroxidation was initiated by the addition of either ADP-complexed Fe3+ or cumene hydroperoxide to isolated rat hepatocytes and the resultant biochemical and morphological alterations investigated. As previously observed with microsomes, malonaldehyde formation was associated with the inactivation of glucose-6-phosphatase. Inhibition of microsomal oxidative drug metabolism was correlated with the release and subsequent inactivation of NADPH-cytochrome c reductase, whereas cytochrome P-450 destruction occurred only in the presence of high concentrations of the organic hydroperoxide which were associated with extensive malonaldehyde formation. Under these conditions there were also marked ultrastructural alterations in the hepatocytes which were not apparent after incubation in the presence of iron (less than or equal to 187 muM Fe3+). The latter treatment was, however, associated with moderate biochemical effects such as glucose-6-phosphatase inactivation and increased membrane permeability. The cellular defence system against lipid peroxidation is discussed and it is concluded that the isolated liver cell system provides a valuable tool for the study of lipid peroxidation and its pathological implications.", "contents": "The consequences of lipid peroxidation in isolated hepatocytes. Lipid peroxidation was initiated by the addition of either ADP-complexed Fe3+ or cumene hydroperoxide to isolated rat hepatocytes and the resultant biochemical and morphological alterations investigated. As previously observed with microsomes, malonaldehyde formation was associated with the inactivation of glucose-6-phosphatase. Inhibition of microsomal oxidative drug metabolism was correlated with the release and subsequent inactivation of NADPH-cytochrome c reductase, whereas cytochrome P-450 destruction occurred only in the presence of high concentrations of the organic hydroperoxide which were associated with extensive malonaldehyde formation. Under these conditions there were also marked ultrastructural alterations in the hepatocytes which were not apparent after incubation in the presence of iron (less than or equal to 187 muM Fe3+). The latter treatment was, however, associated with moderate biochemical effects such as glucose-6-phosphatase inactivation and increased membrane permeability. The cellular defence system against lipid peroxidation is discussed and it is concluded that the isolated liver cell system provides a valuable tool for the study of lipid peroxidation and its pathological implications."} {"id": "PMID:173538", "title": "Microbody of methanol-grown yeasts. Localization of catalase and flavin-dependent alcohol oxidase in the isolated microbody.", "content": "Profuse appearance of microbodies was observed in the cells of methanol-utilizing yeasts in connection with the enhanced catalase activity. These microbodies were isolated successfully by means of sucrose gradient centrifugation from the methanol-grown cells of Kloeckera sp. no. 2201. Localization of a flavin-dependent alcohol oxidase as well as characteristic microbody enzymes (catalase and D-amino acid oxidase) were ascertained in the isolated microbodies, whereas formaldehyde and formate dehydrogenases were detected in the cytoplasmic region. Localization of catalase in the isolated microbody was also demonstrated by the cytochemical technique with 3,3'-diaminobenzidine.", "contents": "Microbody of methanol-grown yeasts. Localization of catalase and flavin-dependent alcohol oxidase in the isolated microbody. Profuse appearance of microbodies was observed in the cells of methanol-utilizing yeasts in connection with the enhanced catalase activity. These microbodies were isolated successfully by means of sucrose gradient centrifugation from the methanol-grown cells of Kloeckera sp. no. 2201. Localization of a flavin-dependent alcohol oxidase as well as characteristic microbody enzymes (catalase and D-amino acid oxidase) were ascertained in the isolated microbodies, whereas formaldehyde and formate dehydrogenases were detected in the cytoplasmic region. Localization of catalase in the isolated microbody was also demonstrated by the cytochemical technique with 3,3'-diaminobenzidine."} {"id": "PMID:173539", "title": "Nuclear protein kinases from murine cells.", "content": "Three protein kinase activities are found in nuclei from three different murine cells (Ehrlich ascites cells, mouse L cells and rat glioma cells). Two of these activities are soluble, one is bound to chromatin. The soluble enzymes are similar, if not identical, to the cytoplasmic protein kinases. The chromatin-bound, adenosine-cyclic-3':5'-monophosphate-independent enzyme is not found in the cytoplasm. This enzyme is composed of one subunit with a molecular weight of 80000-90000. Some biochemical properties of this enzyme are described. A brief description of a nuclear enzyme, which dephosphorylates phosphorylated histones, is also given.", "contents": "Nuclear protein kinases from murine cells. Three protein kinase activities are found in nuclei from three different murine cells (Ehrlich ascites cells, mouse L cells and rat glioma cells). Two of these activities are soluble, one is bound to chromatin. The soluble enzymes are similar, if not identical, to the cytoplasmic protein kinases. The chromatin-bound, adenosine-cyclic-3':5'-monophosphate-independent enzyme is not found in the cytoplasm. This enzyme is composed of one subunit with a molecular weight of 80000-90000. Some biochemical properties of this enzyme are described. A brief description of a nuclear enzyme, which dephosphorylates phosphorylated histones, is also given."} {"id": "PMID:173540", "title": "ADP-ribosylation of DNA-dependent RNA polymerase of Escherichia coli by an NAD+: protein ADP-ribosyltransferase from bacteriophage T4.", "content": "A protein from bacteriophage T4 responsible for the alteration of host DNA-dependent RNA polymerase and absent in T4 alt- phage was purified from T4 phage and enriched from T4-infected cells. It is injected during infection together with the known internal proteins. It has a molecular weight of about 70000 and catalyses the release of nicotinamide and the transfer of the ADP-ribosyl moiety from NAD+ to arginyl residues of various proteins including itself. RNA polymerase from Escherichia coli accepts ADP-ribosyl residues in all four subunits; the alpha subunit reacts with very high specificity. Only half of the alpha subunits are labelled, 45% with one, 5% with two residues. The main product shows the same electrophoretic mobility as alpha subunits altered or modified in vivo. The alpha subunit in modified RNA polymerase is no acceptor.", "contents": "ADP-ribosylation of DNA-dependent RNA polymerase of Escherichia coli by an NAD+: protein ADP-ribosyltransferase from bacteriophage T4. A protein from bacteriophage T4 responsible for the alteration of host DNA-dependent RNA polymerase and absent in T4 alt- phage was purified from T4 phage and enriched from T4-infected cells. It is injected during infection together with the known internal proteins. It has a molecular weight of about 70000 and catalyses the release of nicotinamide and the transfer of the ADP-ribosyl moiety from NAD+ to arginyl residues of various proteins including itself. RNA polymerase from Escherichia coli accepts ADP-ribosyl residues in all four subunits; the alpha subunit reacts with very high specificity. Only half of the alpha subunits are labelled, 45% with one, 5% with two residues. The main product shows the same electrophoretic mobility as alpha subunits altered or modified in vivo. The alpha subunit in modified RNA polymerase is no acceptor."} {"id": "PMID:173541", "title": "Procollagen biosynthesis by embryonic-chick-bone polysomes. Estimation of the relative numbers of active proalpha1 and proalpha2 messenger ribonucleic acids.", "content": "Both total polysomes and polysomes of different size classes isolated from embryonic chick cranial bones were allowed to complete their nascent polypeptide chains in a cell-free system containing rabbit reticulocyte post-ribosomal supernatant fraction. In this system, no de novo initiation of polypeptide synthesis occurred. The product was analysed for relative content of proalpha1 and proalpha2, the precursors of the alpha chains of collagen, by dodecylsulphate-acrylamide gel electrophoresis as well as by paper electrophoresis following tryptic digestion. The results showed that the products of polysome protein synthesis contained proalpha1 and proalpha2 in the 2:1 ratio in which the corresponding alpha chains are present in native collagen, and that proalpha1 and proalpha2 synthesising polysomes are of the same size. These findings, in conjunction with results from a previous report (Vuust, J. and Piez, K.A. (1972) J. Biol. Chem. 247, 856-862) suggest that active messenger ribonucleic acids for the proalpha1 and proalpha2 chains, respectively, are present in the cells in a ratio of 2:1, and that the rates of initiation, elongation, termination and release from polysomes are all identical for the two chains.", "contents": "Procollagen biosynthesis by embryonic-chick-bone polysomes. Estimation of the relative numbers of active proalpha1 and proalpha2 messenger ribonucleic acids. Both total polysomes and polysomes of different size classes isolated from embryonic chick cranial bones were allowed to complete their nascent polypeptide chains in a cell-free system containing rabbit reticulocyte post-ribosomal supernatant fraction. In this system, no de novo initiation of polypeptide synthesis occurred. The product was analysed for relative content of proalpha1 and proalpha2, the precursors of the alpha chains of collagen, by dodecylsulphate-acrylamide gel electrophoresis as well as by paper electrophoresis following tryptic digestion. The results showed that the products of polysome protein synthesis contained proalpha1 and proalpha2 in the 2:1 ratio in which the corresponding alpha chains are present in native collagen, and that proalpha1 and proalpha2 synthesising polysomes are of the same size. These findings, in conjunction with results from a previous report (Vuust, J. and Piez, K.A. (1972) J. Biol. Chem. 247, 856-862) suggest that active messenger ribonucleic acids for the proalpha1 and proalpha2 chains, respectively, are present in the cells in a ratio of 2:1, and that the rates of initiation, elongation, termination and release from polysomes are all identical for the two chains."} {"id": "PMID:173542", "title": "Radiommunoassay for human and chick prolyl hydroxylases.", "content": "A radioimmunoassay is reported for measuring prolyl hydroxylase. The assay is based on the displacement of radioactively-labelled prolyl hydroxylase from its antibody by the non-labelled enzyme, and on the subsequent precipitation of the enzyme-antibody complex by a cellulose-bound second antibody. Pure prolyl hydroxylase was isolated from foetal human or chick embryo tissues by an affinity column procedure usingpoly(L-proline). The enzyme was labelled with tritium using a technique of reductive alkylation with formaldehyde and sodium [3H]borohydride. No conversion of the enzyme tetramer to its monomers was found to take place during the tritiation reaction. Experiments on the dissociation of the non-labelled enzyme indicated that the degree of displacement of the labelled enzyme was similar regardless of whether the non-labelled enzyme was in the tetramer form or in that of the subunit monomers. The sensitivity of the radioimmunoassay is of the order of 5 -- 10 ng immunoreactive prolyl hydroxylase. The concentrations of the immunoreactive prolyl hydroxylase assayed with the present method in human serum and skin and in several chick embryo tissues are reported.", "contents": "Radiommunoassay for human and chick prolyl hydroxylases. A radioimmunoassay is reported for measuring prolyl hydroxylase. The assay is based on the displacement of radioactively-labelled prolyl hydroxylase from its antibody by the non-labelled enzyme, and on the subsequent precipitation of the enzyme-antibody complex by a cellulose-bound second antibody. Pure prolyl hydroxylase was isolated from foetal human or chick embryo tissues by an affinity column procedure usingpoly(L-proline). The enzyme was labelled with tritium using a technique of reductive alkylation with formaldehyde and sodium [3H]borohydride. No conversion of the enzyme tetramer to its monomers was found to take place during the tritiation reaction. Experiments on the dissociation of the non-labelled enzyme indicated that the degree of displacement of the labelled enzyme was similar regardless of whether the non-labelled enzyme was in the tetramer form or in that of the subunit monomers. The sensitivity of the radioimmunoassay is of the order of 5 -- 10 ng immunoreactive prolyl hydroxylase. The concentrations of the immunoreactive prolyl hydroxylase assayed with the present method in human serum and skin and in several chick embryo tissues are reported."} {"id": "PMID:173544", "title": "Kinetics and effect of salts and polyamines on T4 polynucleotide ligase.", "content": "The kinetics of T4 polynucleotide ligase has been investigated at pH 8,20 degrees C and using the double-stranded DNA substrate (dA)n - [(dT)10]n/10. Double-reciprocal plots of initial rates vs substrate concentrations as well as product inhibition studies have indicated that the enzyme reacts according to a ping-pong mechanism. The overall mechanism was found to be non-processive. The true Km for the DNA substrate was 0.6 muM and that of ATP 100 muM. Several attempts were made to reverse the T4 polynucleotide ligase joining reaction using 32-p-labelled (dA)n - [(DT)40]n/40 as substrate. No breakdown of this DNA could be detected. The joining reaction was inhibited by high concentrations, i.e. above approximately 70mM, of salts such as KCl, NaCl, NH4Cl and CsCl. At a concentration of 200 mM almost 100% inhibition was observed. Polyamines also caused inhibition of the enzyme, the most efficient inhibitor being spermine followed by spermidine. At a concentration of 1 mM spermine, virtually no joining took place. Addition of salts or polyamines resulted in a large increase in the apparent Km for the DNA substrate whereas the apparent Km for ATP remained unchanged. It is suggested that the affinity of the enzyme for the DNA substrate is decreased in the presence of inhibiting agents.", "contents": "Kinetics and effect of salts and polyamines on T4 polynucleotide ligase. The kinetics of T4 polynucleotide ligase has been investigated at pH 8,20 degrees C and using the double-stranded DNA substrate (dA)n - [(dT)10]n/10. Double-reciprocal plots of initial rates vs substrate concentrations as well as product inhibition studies have indicated that the enzyme reacts according to a ping-pong mechanism. The overall mechanism was found to be non-processive. The true Km for the DNA substrate was 0.6 muM and that of ATP 100 muM. Several attempts were made to reverse the T4 polynucleotide ligase joining reaction using 32-p-labelled (dA)n - [(DT)40]n/40 as substrate. No breakdown of this DNA could be detected. The joining reaction was inhibited by high concentrations, i.e. above approximately 70mM, of salts such as KCl, NaCl, NH4Cl and CsCl. At a concentration of 200 mM almost 100% inhibition was observed. Polyamines also caused inhibition of the enzyme, the most efficient inhibitor being spermine followed by spermidine. At a concentration of 1 mM spermine, virtually no joining took place. Addition of salts or polyamines resulted in a large increase in the apparent Km for the DNA substrate whereas the apparent Km for ATP remained unchanged. It is suggested that the affinity of the enzyme for the DNA substrate is decreased in the presence of inhibiting agents."} {"id": "PMID:173545", "title": "Nitrogenase from Azotobacter chroococcum. Purification and properties of the component proteins.", "content": "1. A large-scale purification of the nitrogenase components from Azotobacter chroococcum yielded two non-haem iron proteins, both of which were necessary for nitrogenase activity and each had a specific activity of approximately 2000 +/- 300 nmol of acetylene reduced/mg protein per min in the presence of sautrating amounts of the other. This procedure freed the Mo-Fe protein from a protein contaminant which had an electron paramagnetic resonance signal at g = 1.94. 2. Both proteins were purified to homogeneity as determined by disc gel electrophoresis and ultracentrifugal analysis. Both proteins were oxygen-sensitive but not cold-labile. Ultracentrifugal analysis indicated that both proteins dissociated to a slight degree at concentrations below 2 mg/ml. 3. The larger of the two proteins had a molecular weight of 227 000 and contained 1.9 +/- 0.3 atoms of Mo, 23 +/- 2 atoms of Fe, 20 +/- 2 acid-labile sulphide and 47 tryptophan residues/mol. The protein consists of 4 subunits of mol. wt 60 000 (approx.). The reduced protein showed electron paramagmetic resonance signals at g = 4.29, 3.65 and 2.013 but not in the area of g = 5 to 6. Upon oxidation abosrbance increased throughout the visible region of the ultraviolet visible spectrum, with a maximum difference between oxidised and reduced protein occurring at 430 nm. 4. The smaller protein had a molecular weight of 64 000 and contained 4 g-atoms of Fe and 4 acid-labile sulphide groups/mol but no tryptophan. It had two subunits of mol. wt 30 800. The reduced protein showed electron paramagnetic resonance signhe protein retained almost full activity after oxidation with phenazine methosulphate. The ultraviolet visible spectrum of oxidised protein was clearly different from that of the oxygen-inactivated protein: it had a sharp peak at 269 nm and a broad absorbance between 340 and 470 nm with a maximum difference between oxidised and reduced forms at 430 nm. Oxygen-inactivated protein showed a sharp peak at 277.5 nm and broad peaks from 305 to 360, 400 to 425 and 435 to 475 nm. 5. Amino acid analyses of both proteins showed that most common amino acids were present with a preponderance of acidic residues. Analyses of compositional relatedness showed that the nitrogenase proteins from A. chroococcum were most closely related to those from A. vinelandii and least so to those from Clostridium pasteurianum.", "contents": "Nitrogenase from Azotobacter chroococcum. Purification and properties of the component proteins. 1. A large-scale purification of the nitrogenase components from Azotobacter chroococcum yielded two non-haem iron proteins, both of which were necessary for nitrogenase activity and each had a specific activity of approximately 2000 +/- 300 nmol of acetylene reduced/mg protein per min in the presence of sautrating amounts of the other. This procedure freed the Mo-Fe protein from a protein contaminant which had an electron paramagnetic resonance signal at g = 1.94. 2. Both proteins were purified to homogeneity as determined by disc gel electrophoresis and ultracentrifugal analysis. Both proteins were oxygen-sensitive but not cold-labile. Ultracentrifugal analysis indicated that both proteins dissociated to a slight degree at concentrations below 2 mg/ml. 3. The larger of the two proteins had a molecular weight of 227 000 and contained 1.9 +/- 0.3 atoms of Mo, 23 +/- 2 atoms of Fe, 20 +/- 2 acid-labile sulphide and 47 tryptophan residues/mol. The protein consists of 4 subunits of mol. wt 60 000 (approx.). The reduced protein showed electron paramagmetic resonance signals at g = 4.29, 3.65 and 2.013 but not in the area of g = 5 to 6. Upon oxidation abosrbance increased throughout the visible region of the ultraviolet visible spectrum, with a maximum difference between oxidised and reduced protein occurring at 430 nm. 4. The smaller protein had a molecular weight of 64 000 and contained 4 g-atoms of Fe and 4 acid-labile sulphide groups/mol but no tryptophan. It had two subunits of mol. wt 30 800. The reduced protein showed electron paramagnetic resonance signhe protein retained almost full activity after oxidation with phenazine methosulphate. The ultraviolet visible spectrum of oxidised protein was clearly different from that of the oxygen-inactivated protein: it had a sharp peak at 269 nm and a broad absorbance between 340 and 470 nm with a maximum difference between oxidised and reduced forms at 430 nm. Oxygen-inactivated protein showed a sharp peak at 277.5 nm and broad peaks from 305 to 360, 400 to 425 and 435 to 475 nm. 5. Amino acid analyses of both proteins showed that most common amino acids were present with a preponderance of acidic residues. Analyses of compositional relatedness showed that the nitrogenase proteins from A. chroococcum were most closely related to those from A. vinelandii and least so to those from Clostridium pasteurianum."} {"id": "PMID:173546", "title": "Independent regulation of the nuclear and mitochondrial DNA synthesis induced by either Simian virus 40 or serum in mouse fibroblast 3T3 cells.", "content": "Resting cultures of 3T3 cells (an established line of mouse fibroblasts) were released from density inhibition by either infection with Simian virus 40 or addition of serum. The increased rate of thymidine incorporation into DNA, induced by these two agents, was measured in the presence and in the absence of three inhibitory conditions (cycloheximide or dibutyryladenosine 3':5'-monophosphate added to the medium, or lack of anchorage). The inhibition was found to be quite similar in cultures stimulated by virus or serum; under the same conditions, however, the incorporation into mitochondrial DNA was much less inhibited than that into nuclear DNA. The experiments also suggest that new protein synthesis may not be necessary, for either virus or serum, to start the inductive mechanism.", "contents": "Independent regulation of the nuclear and mitochondrial DNA synthesis induced by either Simian virus 40 or serum in mouse fibroblast 3T3 cells. Resting cultures of 3T3 cells (an established line of mouse fibroblasts) were released from density inhibition by either infection with Simian virus 40 or addition of serum. The increased rate of thymidine incorporation into DNA, induced by these two agents, was measured in the presence and in the absence of three inhibitory conditions (cycloheximide or dibutyryladenosine 3':5'-monophosphate added to the medium, or lack of anchorage). The inhibition was found to be quite similar in cultures stimulated by virus or serum; under the same conditions, however, the incorporation into mitochondrial DNA was much less inhibited than that into nuclear DNA. The experiments also suggest that new protein synthesis may not be necessary, for either virus or serum, to start the inductive mechanism."} {"id": "PMID:173547", "title": "Characterization of calf-ovary adenosine;3':5'-monophosphate-dependent protein kinases and adenosine-3':5'-monophosphate-binding proteins.", "content": "Protein phosphokinase activity from the calf ovary cytosol (105000 X g supernatant fraction) has been resolved by chromatography and polyacrylamide gel electrophoresis into two major protein kinases, PK-H1 and PK-H2, both dependent on adenosine 3':5'-monophosphate (cyclic AMP). The enzymes have similar molecular weights (230000) and substrate specificities but differ in their cyclic-AMP-dependency and stimulation by cyclic AMP. The differences have been explained by the presence in PK-H1 of a unique cyclic-AMP-binding protein which has little catalytic activity associated with it. The cyclic-AMP-binding protein has a high affinity for cyclic AMP and in addition is able to inhibit the activity of the isolated catalytic subunit. The ovarian cyclic-AMP-dependent protein kinases have properties similar to those found in other tissues. They can be dissociated into catalytic and regulatory subunits and are inhibited by a heat-stable protein inhibitor isolated from rabbit skeletal muscle. Preincubation of the cytosol with high levels of cyclic AMP resulted in additional cyclic-AMP-dependent protein kinases and cyclic-AMP-binding proteins which include protein kinases and binding proteins of greater than 400 000 molecular weight.", "contents": "Characterization of calf-ovary adenosine;3':5'-monophosphate-dependent protein kinases and adenosine-3':5'-monophosphate-binding proteins. Protein phosphokinase activity from the calf ovary cytosol (105000 X g supernatant fraction) has been resolved by chromatography and polyacrylamide gel electrophoresis into two major protein kinases, PK-H1 and PK-H2, both dependent on adenosine 3':5'-monophosphate (cyclic AMP). The enzymes have similar molecular weights (230000) and substrate specificities but differ in their cyclic-AMP-dependency and stimulation by cyclic AMP. The differences have been explained by the presence in PK-H1 of a unique cyclic-AMP-binding protein which has little catalytic activity associated with it. The cyclic-AMP-binding protein has a high affinity for cyclic AMP and in addition is able to inhibit the activity of the isolated catalytic subunit. The ovarian cyclic-AMP-dependent protein kinases have properties similar to those found in other tissues. They can be dissociated into catalytic and regulatory subunits and are inhibited by a heat-stable protein inhibitor isolated from rabbit skeletal muscle. Preincubation of the cytosol with high levels of cyclic AMP resulted in additional cyclic-AMP-dependent protein kinases and cyclic-AMP-binding proteins which include protein kinases and binding proteins of greater than 400 000 molecular weight."} {"id": "PMID:173548", "title": "Cleavage map of the simian-virus-40 genome by the restriction endonuclease III of Haemopholus aegyptius.", "content": "Enzymic digestion of Simian virus 40 (SV40) DNA with Haemophilus aegyptius restriction endonuclease Hae III results in 10 major and eight minor fragments. These were resolved by electrophoresis on graduated polyacrylamide slab gels. All fragments have been characterized with respect to the size relative to the Haemophilus influenzae Rd fragments (Hind). They were ordered on the SV40 DNA map by means of overlap analysis of the double cleavage products derived from sequential digestion of Hind fragments with Hae III endonuclease and Hae fragments with Hind II + III enzyme, as well as by other reciprocal cleavage experiments, including those involving Haemophilus para-influenzae fragments. In this way the 18 Hae III cleavage sites and the 13 Hind sites have been localized on the circular SV40 DNA map.", "contents": "Cleavage map of the simian-virus-40 genome by the restriction endonuclease III of Haemopholus aegyptius. Enzymic digestion of Simian virus 40 (SV40) DNA with Haemophilus aegyptius restriction endonuclease Hae III results in 10 major and eight minor fragments. These were resolved by electrophoresis on graduated polyacrylamide slab gels. All fragments have been characterized with respect to the size relative to the Haemophilus influenzae Rd fragments (Hind). They were ordered on the SV40 DNA map by means of overlap analysis of the double cleavage products derived from sequential digestion of Hind fragments with Hae III endonuclease and Hae fragments with Hind II + III enzyme, as well as by other reciprocal cleavage experiments, including those involving Haemophilus para-influenzae fragments. In this way the 18 Hae III cleavage sites and the 13 Hind sites have been localized on the circular SV40 DNA map."} {"id": "PMID:173549", "title": "Specific cleavage and physical mapping of simian-virus-40 DNA by the restriction endonuclease of Arthrobacter luteus.", "content": "Simian virus 40 (SV40) DNA (strain 776) is cleaved by the restriction endonuclease from Arthrobacter luteus into 32 specific fragments including 20 large pieces designated Alu-A through T as well as 12 minor products named Alu m1 through m8. These were mapped on the SV40 genome by double digestion experiments. Alu fragments were treated with Hind enzymes and vice versa. Similar reciprocal digestions were also carried out with Hae III enzyme. In this way a detailed cleavage map of the SV40 genome could be constructed.", "contents": "Specific cleavage and physical mapping of simian-virus-40 DNA by the restriction endonuclease of Arthrobacter luteus. Simian virus 40 (SV40) DNA (strain 776) is cleaved by the restriction endonuclease from Arthrobacter luteus into 32 specific fragments including 20 large pieces designated Alu-A through T as well as 12 minor products named Alu m1 through m8. These were mapped on the SV40 genome by double digestion experiments. Alu fragments were treated with Hind enzymes and vice versa. Similar reciprocal digestions were also carried out with Hae III enzyme. In this way a detailed cleavage map of the SV40 genome could be constructed."} {"id": "PMID:173551", "title": "Conformational changes in glycogen phosphorylase studied with a spin-label probe.", "content": "Phosphorylase b and a were covalently modified on essentially one -- SH group per subunit by a spin label 4-(2-iodoacetamido)2,2,6,6-tetramethyl piperidinyloxyl. The labelled enzyme is fully active and exhibits all the characteristics of the native molecule. The electron spin resonance spectrum of the label depends on the nature of the ligand that is bound to the enzyme. This property of the spin label is used to study the interaction between the enzyme (both in the b and a forms) and activators (AMP, IMP, CMP), inhibitors (ADP, ATP, UDPG, glucose 6-phosphate), substrates (phosphate and glucose 1-phosphate) and other ligands (adenosine, beta-glycerol-2-phosphate). The interactions are analysed in terms of the apparent ligand dissociation constants and the multiplicity of conformations that this regulatory enzyme exhibits.", "contents": "Conformational changes in glycogen phosphorylase studied with a spin-label probe. Phosphorylase b and a were covalently modified on essentially one -- SH group per subunit by a spin label 4-(2-iodoacetamido)2,2,6,6-tetramethyl piperidinyloxyl. The labelled enzyme is fully active and exhibits all the characteristics of the native molecule. The electron spin resonance spectrum of the label depends on the nature of the ligand that is bound to the enzyme. This property of the spin label is used to study the interaction between the enzyme (both in the b and a forms) and activators (AMP, IMP, CMP), inhibitors (ADP, ATP, UDPG, glucose 6-phosphate), substrates (phosphate and glucose 1-phosphate) and other ligands (adenosine, beta-glycerol-2-phosphate). The interactions are analysed in terms of the apparent ligand dissociation constants and the multiplicity of conformations that this regulatory enzyme exhibits."} {"id": "PMID:173552", "title": "Heterotropic interactions of ligands with phosphorylase b.", "content": "1. The interaction of rabbit muscle glycogen phosphorylase b with pairs of ligands has been examined. 2. The electron spin resonance spectrum of a spin label, covalently attached to the protein, provided information about dissociation constants, formation of ternary complexes and both negative and positive interactions between different ligand pairs. 3. AMP competes with a series of nucleotides (ADP, ATP, CMP aand cytosine) but with adenosine a ternary enzyme - AMP - adenosine complex can be formed. 4. ADP binding is tight and ADP inhibits the AMP activation of phosphorylase b in a physiologically important concentration range. 5. The substrates glucose 1-phosphate and glycogen tighten AMP binding in the ternary complex as does the competitive inhibitor UDPG. Inorganic phosphate is different in this respect. Gluconolactone, a transition state analogue, competes with glucose 1-phosphate (but not with glycogen) but does not prevent completely the binding of the sugar phosphate. 6. The effect of glucose b-phosphate on phosphorylase is rather complex as it 'formally competes' with both AMP and UDPG probably mediated by a conformational changes and not by 'direct' interactions with these two ligands. Glycerol 2-phosphate, a commonly used buffer for phosphorylase, also shows complex interactions.", "contents": "Heterotropic interactions of ligands with phosphorylase b. 1. The interaction of rabbit muscle glycogen phosphorylase b with pairs of ligands has been examined. 2. The electron spin resonance spectrum of a spin label, covalently attached to the protein, provided information about dissociation constants, formation of ternary complexes and both negative and positive interactions between different ligand pairs. 3. AMP competes with a series of nucleotides (ADP, ATP, CMP aand cytosine) but with adenosine a ternary enzyme - AMP - adenosine complex can be formed. 4. ADP binding is tight and ADP inhibits the AMP activation of phosphorylase b in a physiologically important concentration range. 5. The substrates glucose 1-phosphate and glycogen tighten AMP binding in the ternary complex as does the competitive inhibitor UDPG. Inorganic phosphate is different in this respect. Gluconolactone, a transition state analogue, competes with glucose 1-phosphate (but not with glycogen) but does not prevent completely the binding of the sugar phosphate. 6. The effect of glucose b-phosphate on phosphorylase is rather complex as it 'formally competes' with both AMP and UDPG probably mediated by a conformational changes and not by 'direct' interactions with these two ligands. Glycerol 2-phosphate, a commonly used buffer for phosphorylase, also shows complex interactions."} {"id": "PMID:173553", "title": "Localization in yeast mitochondrial DNA of mutations expressed in a deficiency of cytochrome oxidase and/or coenzyme QH2-cytochrome c reductase.", "content": "1. Three methods are described for the genetic analysis of yeast cytoplasmic mutants (mit- mutants) lacking cytochrome oxidase or coenzyme QH2-cytochrome c reductase. The procedures permit mutations in mitochondrial DNA to be mapped relative to each other and with respect to drug-resistant markers. The first method is based upon the finding that crosses of mit- mutants with some but not other isonuclear q- mutants lead to the restoration of respiratory functions. Thus a segment of mitochondrial DNA corresponding to a given mit- mutation or to a set of mutations can be delineated. The second method is based on the appearance of wild-type progeny in mit- X mit- crosses. The third one is based on the analysis of various recombinant classes issued from crosses between mit-, drug-sensitive and mit+, drug-resistant mutants. Representative genetic markers of the RIBI, OLII, OLI2 and PAR1 loci were used for this purpose. 2. The three methods when applied to the study of 48 mit- mutants gave coherent results. At least three distinct regions on mitochondrial DNA in which mutations cause loss of functional cytochrome oxidase have been established. A fourth region represented by closely clustered mutants lacking coenzyme QH2-cytochrome c reductase and spectrally detectable cytochrome b has also been studied. 3. The three genetic regions of cytochrome oxidase and the cytochrome b region were localized by the third method on the circular map, in spans of mitochondrial DNA defined by the drug-resistant markers. The results obtained by this method were confirmed by analysis of the crosses between selected mit- mutants and a large number of q- clones whose retained segments of mitochondrial DNA contained various combinations of drug-resistant markers. 4. All the genetic data indicate that the various regions studied are dispersed on the mitochondrial genome and in some instances regions or clusters of closely linked mutations involved in the same respiratory function (cytochrome oxidase) are separated by other regions which code for entirely different functions such as ribosomal RNA.", "contents": "Localization in yeast mitochondrial DNA of mutations expressed in a deficiency of cytochrome oxidase and/or coenzyme QH2-cytochrome c reductase. 1. Three methods are described for the genetic analysis of yeast cytoplasmic mutants (mit- mutants) lacking cytochrome oxidase or coenzyme QH2-cytochrome c reductase. The procedures permit mutations in mitochondrial DNA to be mapped relative to each other and with respect to drug-resistant markers. The first method is based upon the finding that crosses of mit- mutants with some but not other isonuclear q- mutants lead to the restoration of respiratory functions. Thus a segment of mitochondrial DNA corresponding to a given mit- mutation or to a set of mutations can be delineated. The second method is based on the appearance of wild-type progeny in mit- X mit- crosses. The third one is based on the analysis of various recombinant classes issued from crosses between mit-, drug-sensitive and mit+, drug-resistant mutants. Representative genetic markers of the RIBI, OLII, OLI2 and PAR1 loci were used for this purpose. 2. The three methods when applied to the study of 48 mit- mutants gave coherent results. At least three distinct regions on mitochondrial DNA in which mutations cause loss of functional cytochrome oxidase have been established. A fourth region represented by closely clustered mutants lacking coenzyme QH2-cytochrome c reductase and spectrally detectable cytochrome b has also been studied. 3. The three genetic regions of cytochrome oxidase and the cytochrome b region were localized by the third method on the circular map, in spans of mitochondrial DNA defined by the drug-resistant markers. The results obtained by this method were confirmed by analysis of the crosses between selected mit- mutants and a large number of q- clones whose retained segments of mitochondrial DNA contained various combinations of drug-resistant markers. 4. All the genetic data indicate that the various regions studied are dispersed on the mitochondrial genome and in some instances regions or clusters of closely linked mutations involved in the same respiratory function (cytochrome oxidase) are separated by other regions which code for entirely different functions such as ribosomal RNA."} {"id": "PMID:173554", "title": "Activity of the 30-S CsCl core in elongation-factor-dependent GTP hydrolysis.", "content": "The activity of a 30-S CsCl core lacking proteins S1, S2, S3, S5, S9, S10, S14, S20 and S21 has been studied in the ribosome-dependent FTPase reactions in the presence of the 50-S subunit with and without methanol. Without methanol, the 30-S CsCl core was unable to sustain GTPase activity dependent on elongation factor G (EF-G), while it was only slightly active in the presence of elongation factor T (EF-T). With EF-T, addition of methanol induced in the presence of either 30-S subunits or 30-S CsCl cores an activity which was more than 10-fold higher than that observed with the 30-S subunit in the absence of methanol. Methanol lowered the Mg2+ optimum of the EF-T-dependent GTPase reaction from approximately 20 mM to approximately 10 mM. In the absence of methanol the EF-G-dependent (GTPase reaction at low concentration of monovalent cations depends on the 50-S subunit alone (30-S-uncoupled EF-G GTPase). Addition of the intact 30-S subunit but not of its CsCl core abolished inhibition of the 30-S-uncoupled EF-G-GTPase by NH4+. The 30-S CsCl core caused the same effect as the 30-S subunit when methanol was present. 30-S-uncoupled EF-G GTPase activity was lower than the GTPase activity dependent on 30-S plus 50-S subunits at [EF-G]/[50-S] below 5 but was considerably higher in the presence of a large excess of EF-G. In the presence of methanol the 30-S CsCl core behaved similarly to the 30-S subunit. Our results indicate that the action of the 30-S subunit in elongation-factor-dependent GTPases is supported by structural features that are preserved in the 30-S CsCl core. The 30-S split proteins are therefore not essential for EF-G and EF-T activities in the hydrolysis of GTP. With EF-T, in all conditions tested association of the ribosomal subunits appeared to accompany GTPase activity. Association seems also to be a prerequisite of the EF-G GTPase activity that depends on both ribosomal subunits.", "contents": "Activity of the 30-S CsCl core in elongation-factor-dependent GTP hydrolysis. The activity of a 30-S CsCl core lacking proteins S1, S2, S3, S5, S9, S10, S14, S20 and S21 has been studied in the ribosome-dependent FTPase reactions in the presence of the 50-S subunit with and without methanol. Without methanol, the 30-S CsCl core was unable to sustain GTPase activity dependent on elongation factor G (EF-G), while it was only slightly active in the presence of elongation factor T (EF-T). With EF-T, addition of methanol induced in the presence of either 30-S subunits or 30-S CsCl cores an activity which was more than 10-fold higher than that observed with the 30-S subunit in the absence of methanol. Methanol lowered the Mg2+ optimum of the EF-T-dependent GTPase reaction from approximately 20 mM to approximately 10 mM. In the absence of methanol the EF-G-dependent (GTPase reaction at low concentration of monovalent cations depends on the 50-S subunit alone (30-S-uncoupled EF-G GTPase). Addition of the intact 30-S subunit but not of its CsCl core abolished inhibition of the 30-S-uncoupled EF-G-GTPase by NH4+. The 30-S CsCl core caused the same effect as the 30-S subunit when methanol was present. 30-S-uncoupled EF-G GTPase activity was lower than the GTPase activity dependent on 30-S plus 50-S subunits at [EF-G]/[50-S] below 5 but was considerably higher in the presence of a large excess of EF-G. In the presence of methanol the 30-S CsCl core behaved similarly to the 30-S subunit. Our results indicate that the action of the 30-S subunit in elongation-factor-dependent GTPases is supported by structural features that are preserved in the 30-S CsCl core. The 30-S split proteins are therefore not essential for EF-G and EF-T activities in the hydrolysis of GTP. With EF-T, in all conditions tested association of the ribosomal subunits appeared to accompany GTPase activity. Association seems also to be a prerequisite of the EF-G GTPase activity that depends on both ribosomal subunits."} {"id": "PMID:173555", "title": "The involvement of cytochrome P-450 in hepatic microsomal steroid hydroxylation reactions supported by sodium periodate, sodium chlorite, and organic hydroperoxides.", "content": "The mechanism of steroid hydroxylation in rat liver microsomes has been investigated by employing NaIO4, NaClO2, and various organic hydroperoxides as hydroxylating agents and comparing the reaction rates and steroid products formed with those of the NADPH-dependent reaction. Androstenedione, testosterone, progesterone, and 17beta-estradiol were found to act as good substrates. NaIO4 was by far the most effective hydroxylating agent followed by cumene hydroperoxide, NADPH, NaClO2, pregnenolone 17alpha-hydroperoxide, tert-butyl hydroperoxide, and linoleic acid hydroperoxide. Androstenedione was chosen as the model substrate for inducer and inhibitor studies. The steroid was converted to its respective 6beta-, 7alpha, 15-, and 16alpha-hydroxy derivatives when incubated with microsomal fractions fortified with hydroxylating agent. Evidence for cytochrome P-450 involvement in androstenedione hydroxylation included a marked inhibition by substrates and modifiers of cytochrome P-450 and by reagents which convert cytochrome P-450 to cytochrome P-420. The ratios of the steroid products varied according to the type of hydroxylating agent used and were also modified by in vivo phenobarbital pretreatment. It was suggested that multiple forms of cytochrome P-450 exhibiting different affinities for hydroxylating agent are responsible for these different ratios. Horse-radish peroxidase, catalase, and metmyoglobin could not catalyze androstenedione hydroxylation. Addition of NaIO4, NaClO2, cumene hydroperoxide and other organic hydroperoxides to microsomal suspensions resulted in the appearance of a transient spectral change in the difference spectrum characterized by a peak at about 440 nm and a trough at 420 nm. The efficiency of these oxidizing agents in promoting steroid hydroxylation in microsomes appeared to be related to their effectiveness in eliciting the spectral complex. Electron donors, substrates, and modifiers of cytochrome P-450 greatly diminished the magnitude of the spectral change. It is proposed that NaIO4, NaClO2, and organic hydroperoxides promote steroid hydroxylation by forming a transient ferryl ion (compound I) of cytochrome P-450 which may be the common intermediate hydroxylating species involved in hydroxylations catalyzed by cytochrome P-450.", "contents": "The involvement of cytochrome P-450 in hepatic microsomal steroid hydroxylation reactions supported by sodium periodate, sodium chlorite, and organic hydroperoxides. The mechanism of steroid hydroxylation in rat liver microsomes has been investigated by employing NaIO4, NaClO2, and various organic hydroperoxides as hydroxylating agents and comparing the reaction rates and steroid products formed with those of the NADPH-dependent reaction. Androstenedione, testosterone, progesterone, and 17beta-estradiol were found to act as good substrates. NaIO4 was by far the most effective hydroxylating agent followed by cumene hydroperoxide, NADPH, NaClO2, pregnenolone 17alpha-hydroperoxide, tert-butyl hydroperoxide, and linoleic acid hydroperoxide. Androstenedione was chosen as the model substrate for inducer and inhibitor studies. The steroid was converted to its respective 6beta-, 7alpha, 15-, and 16alpha-hydroxy derivatives when incubated with microsomal fractions fortified with hydroxylating agent. Evidence for cytochrome P-450 involvement in androstenedione hydroxylation included a marked inhibition by substrates and modifiers of cytochrome P-450 and by reagents which convert cytochrome P-450 to cytochrome P-420. The ratios of the steroid products varied according to the type of hydroxylating agent used and were also modified by in vivo phenobarbital pretreatment. It was suggested that multiple forms of cytochrome P-450 exhibiting different affinities for hydroxylating agent are responsible for these different ratios. Horse-radish peroxidase, catalase, and metmyoglobin could not catalyze androstenedione hydroxylation. Addition of NaIO4, NaClO2, cumene hydroperoxide and other organic hydroperoxides to microsomal suspensions resulted in the appearance of a transient spectral change in the difference spectrum characterized by a peak at about 440 nm and a trough at 420 nm. The efficiency of these oxidizing agents in promoting steroid hydroxylation in microsomes appeared to be related to their effectiveness in eliciting the spectral complex. Electron donors, substrates, and modifiers of cytochrome P-450 greatly diminished the magnitude of the spectral change. It is proposed that NaIO4, NaClO2, and organic hydroperoxides promote steroid hydroxylation by forming a transient ferryl ion (compound I) of cytochrome P-450 which may be the common intermediate hydroxylating species involved in hydroxylations catalyzed by cytochrome P-450."} {"id": "PMID:173562", "title": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. I. Responses in the brachium pontis.", "content": "Cerebrally-induced responses of pontine nuclei cells (PN cells) were studied in cats anesthetized with pentobarbitone sodium and with the midbrain transected bilaterally sparing only the cerebral penuncles. After stimulating the subcortical white matter, the internal capsule or the cerebral peduncle, mass potentials were recorded from the cut end of fibres in the brachium pontis (BP) and in the pyramid at the level of the trapezoid body. These potentials were regarded as indicating, respectively, the size of an output volley of PN cells and the size of its causative input volley through the pyramidal tract. BP responses consisted of short- and long-latency potentials which were caused by fast and slow conducting pyramidal tract volleys, respectively. The input-output relations for fast component responses took a characteristic S-shaped form resembling those obtained from the monosynaptic spinal reflex. The input-output relations for slow component responses were almost linear. Both fast and slow BP responses were remarkably potentiated after single or relatively brief repetitive peduncular stimulation, but were depressed after long-lasting high-frequency activation. During repetitive stimulation with varied frequencies, fast and slow BP responses showed different patterns of frequency-dependence of their amplitudes. These results suggest the existence of two separate transmission lines with different properties in cerebro-ponto-cerebellar pathways.", "contents": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. I. Responses in the brachium pontis. Cerebrally-induced responses of pontine nuclei cells (PN cells) were studied in cats anesthetized with pentobarbitone sodium and with the midbrain transected bilaterally sparing only the cerebral penuncles. After stimulating the subcortical white matter, the internal capsule or the cerebral peduncle, mass potentials were recorded from the cut end of fibres in the brachium pontis (BP) and in the pyramid at the level of the trapezoid body. These potentials were regarded as indicating, respectively, the size of an output volley of PN cells and the size of its causative input volley through the pyramidal tract. BP responses consisted of short- and long-latency potentials which were caused by fast and slow conducting pyramidal tract volleys, respectively. The input-output relations for fast component responses took a characteristic S-shaped form resembling those obtained from the monosynaptic spinal reflex. The input-output relations for slow component responses were almost linear. Both fast and slow BP responses were remarkably potentiated after single or relatively brief repetitive peduncular stimulation, but were depressed after long-lasting high-frequency activation. During repetitive stimulation with varied frequencies, fast and slow BP responses showed different patterns of frequency-dependence of their amplitudes. These results suggest the existence of two separate transmission lines with different properties in cerebro-ponto-cerebellar pathways."} {"id": "PMID:173563", "title": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. II. Responses of single cells in the pontine nuclei.", "content": "Extracellular and intracellular recordings were made from single cells in the pontine nuclei (PN) of the cat. PN cells were identified by antidromic invasion from the cerebellum by stimulating either the brachium pontis (BP) or the white matter near the cerebellar nuclei. The cerebrally-induced impulses excited PN cells postsynaptically with a monosynaptic latency. Both fast and slow conducting cortical fibres contributed to the corticopontine excitation, so that the latency varied over a wide range. Measurements of the latencies for antidromic and corticopontine excitation and of the distances between stimulated sites permitted the calcuation of conduction velocities of PN cell axons and of their cortical input fibres. PN cells with fast conducting axons received convergence from both fast and slow cortical fibres, whereas PN cells with slow axons were innervated only by slow cortical fibres. The majority of PN cells were also excited by stimulating the medullary pyramid through collaterals of the pyramidal tract. Evidence of abundant pyramidal collaterals was provided by the collision technique. The functional role of the PN is discussed in connection with the cerebro-cerebellar loop circuits.", "contents": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. II. Responses of single cells in the pontine nuclei. Extracellular and intracellular recordings were made from single cells in the pontine nuclei (PN) of the cat. PN cells were identified by antidromic invasion from the cerebellum by stimulating either the brachium pontis (BP) or the white matter near the cerebellar nuclei. The cerebrally-induced impulses excited PN cells postsynaptically with a monosynaptic latency. Both fast and slow conducting cortical fibres contributed to the corticopontine excitation, so that the latency varied over a wide range. Measurements of the latencies for antidromic and corticopontine excitation and of the distances between stimulated sites permitted the calcuation of conduction velocities of PN cell axons and of their cortical input fibres. PN cells with fast conducting axons received convergence from both fast and slow cortical fibres, whereas PN cells with slow axons were innervated only by slow cortical fibres. The majority of PN cells were also excited by stimulating the medullary pyramid through collaterals of the pyramidal tract. Evidence of abundant pyramidal collaterals was provided by the collision technique. The functional role of the PN is discussed in connection with the cerebro-cerebellar loop circuits."} {"id": "PMID:173564", "title": "The vestibulospinal tract: crossed and uncrossed effects on hindlimb motoneurones in the cat.", "content": "Effects produced by stimulation of Deiters' nucleus on contralateral hindlimb motoneurones were investigated in the cat with intracellular and monosynaptic reflex recording. Polysynaptic PSPs were evoked in all species of motoneurone examined. The minimal synaptic linkage was found to be disynaptic in the excitatory path and prisynaptic in the inhibitory path. Experiments with various lesions to the spinal funiculus and those with mapping of the stimulated sites in the brain stem showed that the effects were evoked almost exclusively via the lateral vestibulospinal tract of the stimulated side. The crossed effects were excitatory in extensor motoneurones of all species studied except for hip extensors (ABSm) in which EPSPs and/or IPSPs were evoked. The effects on flexors, by contrast, were not simple and consisted of EPSPs, IPSPs or a mixture of both. The difference in effects depended, though not entirely, on the species of motor nucleus. Between the excitatory and inhibitory effects on knee flexor (PBSt) motoneurones the former predominated under chloralose and the latter under pentobarbital anaesthesia. By recording PSPs evoked from the two vestibulospinal tracts in the same motoneurone, the convergence pattern and the magnitude of effects from the two tracts were studied. The interneuronal organization of the crossed vestibulo-motoneuronel pathway and its functional significance are discussed.", "contents": "The vestibulospinal tract: crossed and uncrossed effects on hindlimb motoneurones in the cat. Effects produced by stimulation of Deiters' nucleus on contralateral hindlimb motoneurones were investigated in the cat with intracellular and monosynaptic reflex recording. Polysynaptic PSPs were evoked in all species of motoneurone examined. The minimal synaptic linkage was found to be disynaptic in the excitatory path and prisynaptic in the inhibitory path. Experiments with various lesions to the spinal funiculus and those with mapping of the stimulated sites in the brain stem showed that the effects were evoked almost exclusively via the lateral vestibulospinal tract of the stimulated side. The crossed effects were excitatory in extensor motoneurones of all species studied except for hip extensors (ABSm) in which EPSPs and/or IPSPs were evoked. The effects on flexors, by contrast, were not simple and consisted of EPSPs, IPSPs or a mixture of both. The difference in effects depended, though not entirely, on the species of motor nucleus. Between the excitatory and inhibitory effects on knee flexor (PBSt) motoneurones the former predominated under chloralose and the latter under pentobarbital anaesthesia. By recording PSPs evoked from the two vestibulospinal tracts in the same motoneurone, the convergence pattern and the magnitude of effects from the two tracts were studied. The interneuronal organization of the crossed vestibulo-motoneuronel pathway and its functional significance are discussed."} {"id": "PMID:173567", "title": "Interaction between dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and cyclic adenosine-3',5'-monophosphate in neoplastic and normal human mammary tissue.", "content": "When total DHEA, G-6-PDH activity, and c-AMP were determined in human neoplastic mammary tissue and corresponding normal tissue the G-6-PDH activity in the former tissue greatly exceeded that found in normal tissue. On the other hand, a remarkable decrease of total DHEA and c-AMP could be detected in cancer tissue, hinting at the participation of DHEA in the intracellular regulation of G-6-PDH and c-AMP levels.", "contents": "Interaction between dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and cyclic adenosine-3',5'-monophosphate in neoplastic and normal human mammary tissue. When total DHEA, G-6-PDH activity, and c-AMP were determined in human neoplastic mammary tissue and corresponding normal tissue the G-6-PDH activity in the former tissue greatly exceeded that found in normal tissue. On the other hand, a remarkable decrease of total DHEA and c-AMP could be detected in cancer tissue, hinting at the participation of DHEA in the intracellular regulation of G-6-PDH and c-AMP levels."} {"id": "PMID:173568", "title": "Changes in the apoprotein composition of very low density lipoproteins in man following eating.", "content": "The concentrations of certain of the very low density human serum lipoprotein apoproteins were found to increase following a meal, while the concentrations of the majority of the apoproteins were found to be unaffected.", "contents": "Changes in the apoprotein composition of very low density lipoproteins in man following eating. The concentrations of certain of the very low density human serum lipoprotein apoproteins were found to increase following a meal, while the concentrations of the majority of the apoproteins were found to be unaffected."} {"id": "PMID:173569", "title": "Polycationic modified polypeptides enhancing poly I:C induced viral resistance.", "content": "Polycationic modified derivatives of polyglutamic acid are at least as good enhancers of poly I:C induced viral resistance in various cell cultures as are DEAE-dextran or poly-L-lysine.", "contents": "Polycationic modified polypeptides enhancing poly I:C induced viral resistance. Polycationic modified derivatives of polyglutamic acid are at least as good enhancers of poly I:C induced viral resistance in various cell cultures as are DEAE-dextran or poly-L-lysine."} {"id": "PMID:173571", "title": "Depression of humoral and cell-mediated immune responses by coxsackieviruses in mice.", "content": "Adult mice infected with coxsackieviruses A-15, B-1, B-2, B-4 and B-6 showed depressed antibody responses to unrelated antigens; mice infected with coxsackievirus B-3 developed reduced humoral and cell-mediated immune responses. These findings might have clinical and epidemiological implications.", "contents": "Depression of humoral and cell-mediated immune responses by coxsackieviruses in mice. Adult mice infected with coxsackieviruses A-15, B-1, B-2, B-4 and B-6 showed depressed antibody responses to unrelated antigens; mice infected with coxsackievirus B-3 developed reduced humoral and cell-mediated immune responses. These findings might have clinical and epidemiological implications."} {"id": "PMID:173572", "title": "Distribution of glycerophosphorylcholine diesterase in rat brain.", "content": "The distribution of glycerylphosphorylcholine diesterase in the rat brain has been examined. The enzyme was evenly distributed throughout the brain but was localized in the synaptosome (nerve ending) fraction which was prepared by ultracentrifugation.", "contents": "Distribution of glycerophosphorylcholine diesterase in rat brain. The distribution of glycerylphosphorylcholine diesterase in the rat brain has been examined. The enzyme was evenly distributed throughout the brain but was localized in the synaptosome (nerve ending) fraction which was prepared by ultracentrifugation."} {"id": "PMID:173573", "title": "Creatinine metabolism by Clostridium welchii isolated from human faeces.", "content": "A Clostridium welchii has been isolated from human faeces which can deaminate creatinine to N-methyl hydantoin. Evidence suggests the reaction is inducible since the rate of conversion is increased by growth of the organism in creatinine-rich media.", "contents": "Creatinine metabolism by Clostridium welchii isolated from human faeces. A Clostridium welchii has been isolated from human faeces which can deaminate creatinine to N-methyl hydantoin. Evidence suggests the reaction is inducible since the rate of conversion is increased by growth of the organism in creatinine-rich media."} {"id": "PMID:173574", "title": "Effect of vitamin A on tumor development in burned, unburned, and glucocorticoid-treated mice inoculated with an oncogenic virus.", "content": "High doses of vitamin A decreased the severity of tumor development in mice inoculated with a murine sarcoma virus; the same doses of vitamin A had no effect on the increased tumorigenesis seen in animals severely stressed with thermal injury or the increased tumorigenesis induced by exogenous glucocorticoid administration.", "contents": "Effect of vitamin A on tumor development in burned, unburned, and glucocorticoid-treated mice inoculated with an oncogenic virus. High doses of vitamin A decreased the severity of tumor development in mice inoculated with a murine sarcoma virus; the same doses of vitamin A had no effect on the increased tumorigenesis seen in animals severely stressed with thermal injury or the increased tumorigenesis induced by exogenous glucocorticoid administration."} {"id": "PMID:173575", "title": "Variations of cyclic nucleotide monophosphate levels during spontaneous uterine contractions.", "content": "Oscillations on the concentrations of cyclic nucliotides occurred during spontaneous rhythmic contractions in rat uterus. The levels of cyclic GMP and cyclic AMP were highest at the beginning of the contraction respectively the relaxation.", "contents": "Variations of cyclic nucleotide monophosphate levels during spontaneous uterine contractions. Oscillations on the concentrations of cyclic nucliotides occurred during spontaneous rhythmic contractions in rat uterus. The levels of cyclic GMP and cyclic AMP were highest at the beginning of the contraction respectively the relaxation."} {"id": "PMID:173577", "title": "Respiratory inhibition and reversible fusion of frog blastomeres.", "content": "Rotenone and high doses of chloramphenicol, both of which specifically inhibit electron transport between NADH and flavoprotein in the respiratory chain, caused fully separated Rana pipiens blastomeres to refuse, as shown by syncytium counts on embryos reconstructed from serial sections. With chloramphenicol, the effect was completely reversible: re-cleavage and normal development followed drug removal. The blastomere fusion effect was not produced by the succinic dehydrogenase-specific respiratory inhibitor, thenoyltrifluoroacetone, nor by a non-mitochondrial protein synthesis inhibitor, cycloheximide, both of which instead produced simple arrest of cleavage.", "contents": "Respiratory inhibition and reversible fusion of frog blastomeres. Rotenone and high doses of chloramphenicol, both of which specifically inhibit electron transport between NADH and flavoprotein in the respiratory chain, caused fully separated Rana pipiens blastomeres to refuse, as shown by syncytium counts on embryos reconstructed from serial sections. With chloramphenicol, the effect was completely reversible: re-cleavage and normal development followed drug removal. The blastomere fusion effect was not produced by the succinic dehydrogenase-specific respiratory inhibitor, thenoyltrifluoroacetone, nor by a non-mitochondrial protein synthesis inhibitor, cycloheximide, both of which instead produced simple arrest of cleavage."} {"id": "PMID:173578", "title": "A technical improvement in the radioimmunoassay of cyclic-AMP.", "content": "An improvement in the technique for the radioimmunoassay of cyclic-AMP, wherein ammonium sulfate precipitation is replaced with zirconyl phosphate gel, is presented. This substitution produces a more stable pellet than that obtained with ammonium sulfate. This greatly reduces a potential source of error due to pellet instability.", "contents": "A technical improvement in the radioimmunoassay of cyclic-AMP. An improvement in the technique for the radioimmunoassay of cyclic-AMP, wherein ammonium sulfate precipitation is replaced with zirconyl phosphate gel, is presented. This substitution produces a more stable pellet than that obtained with ammonium sulfate. This greatly reduces a potential source of error due to pellet instability."} {"id": "PMID:173584", "title": "Aspects of the biochemical toxicology of cadmium.", "content": "Cadmium, in addition to producing a variety of toxic manifestations, is known to accumulate in certain \"target\" organs which include liver and kidney where histological and functional damage becomes apparent. The daily intraperitoneal injection of cadmium chloride for 21 or 45 days stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase elevated blood glucose and urea, and lowered hepatic glycogen in rats. Whereas chronic Cd treatment failed to alter adenosine-3', 5'-monophosphate phosphodiesterase (PDE) activity, cyclic AMP (cAMY and the activity of basal and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased. However, the cAMP binding to hepatic protein kinase was decreased as was the kinase activity ration. An acute dose of Cd decreased hepatic glycogen content and increased blood glucose, serum urea, and hepatic cAMP. Chronic exposure to Cd induced adrenal hypertrophy and augmented adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. This treatment decreased prostatic and testicular weights of mature rats. Although cAMP as well as AC activity of the prostate gland were reduced, cAMP binding to the prostatic protein kinase was increased as was the activity of the cAMP-dependent form of the enzyme. Testicular AC and PDE activities, however, were stimulated, although cAMP remained unaffected. Whereas the activities of the cAMP-dependent and the independent forms of testicular protein kinase were significantly depressed, the binding of cAMP to protein kinase from testes of Cd-treated rats was not affected. In most cases, the observed metabolic alterations persisted up to 28 days on cessation of Cd administration. Subacute Cd treatment suppressed pancreatic function as evidenced by lowered serum immunoreactive insulin (IRI) in presence of hyperglycemia, as well as by partial inhibition of phentolamine-stimulated increases in serum IRI. Although chronic Cd treatment failed to alter the concentration of brain stem norepinephrine and cerebrocortical acetylcholine esterase activity, serotonin levels of brain stem were depressed and the concentration of striatal dopamine and cerebrocortical acetylcholine were significantly elevated when compared with the values seen in control nonexposed animals.", "contents": "Aspects of the biochemical toxicology of cadmium. Cadmium, in addition to producing a variety of toxic manifestations, is known to accumulate in certain \"target\" organs which include liver and kidney where histological and functional damage becomes apparent. The daily intraperitoneal injection of cadmium chloride for 21 or 45 days stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase elevated blood glucose and urea, and lowered hepatic glycogen in rats. Whereas chronic Cd treatment failed to alter adenosine-3', 5'-monophosphate phosphodiesterase (PDE) activity, cyclic AMP (cAMY and the activity of basal and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased. However, the cAMP binding to hepatic protein kinase was decreased as was the kinase activity ration. An acute dose of Cd decreased hepatic glycogen content and increased blood glucose, serum urea, and hepatic cAMP. Chronic exposure to Cd induced adrenal hypertrophy and augmented adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. This treatment decreased prostatic and testicular weights of mature rats. Although cAMP as well as AC activity of the prostate gland were reduced, cAMP binding to the prostatic protein kinase was increased as was the activity of the cAMP-dependent form of the enzyme. Testicular AC and PDE activities, however, were stimulated, although cAMP remained unaffected. Whereas the activities of the cAMP-dependent and the independent forms of testicular protein kinase were significantly depressed, the binding of cAMP to protein kinase from testes of Cd-treated rats was not affected. In most cases, the observed metabolic alterations persisted up to 28 days on cessation of Cd administration. Subacute Cd treatment suppressed pancreatic function as evidenced by lowered serum immunoreactive insulin (IRI) in presence of hyperglycemia, as well as by partial inhibition of phentolamine-stimulated increases in serum IRI. Although chronic Cd treatment failed to alter the concentration of brain stem norepinephrine and cerebrocortical acetylcholine esterase activity, serotonin levels of brain stem were depressed and the concentration of striatal dopamine and cerebrocortical acetylcholine were significantly elevated when compared with the values seen in control nonexposed animals."} {"id": "PMID:173587", "title": "A case of xanthomatosis and hyperlipoproteinemia type V propably induced by overdosage of insulin.", "content": "A woman, aged 46 years, with a hyperlipoproteinemia phenotype V, an unusual type of xanthomatosis, as well as lipemia retinalis, diabetes mellitus, and nephropathia, is discussed. The withdrawal of 64 IU insulin and the institution of a hypocaloric diabetes diet resulted in the disappearance of the skin lesions and a regression of the eye lesion. During this treatment the total lipid-level became almost normal (6,965 mg% before treatment and 947 mg% after 10 weeks). The chylomicrons disappeared but the VLDL content remained relatively and absolutely elevated, as in type IV hyperlipoproteinemia.", "contents": "A case of xanthomatosis and hyperlipoproteinemia type V propably induced by overdosage of insulin. A woman, aged 46 years, with a hyperlipoproteinemia phenotype V, an unusual type of xanthomatosis, as well as lipemia retinalis, diabetes mellitus, and nephropathia, is discussed. The withdrawal of 64 IU insulin and the institution of a hypocaloric diabetes diet resulted in the disappearance of the skin lesions and a regression of the eye lesion. During this treatment the total lipid-level became almost normal (6,965 mg% before treatment and 947 mg% after 10 weeks). The chylomicrons disappeared but the VLDL content remained relatively and absolutely elevated, as in type IV hyperlipoproteinemia."} {"id": "PMID:173588", "title": "Differentiation between steroid hormone receptors CBG and SHBG in human target organ extracts by a single-step assay.", "content": "The steroid complexes of (plasma) corticosteroid-binding globulin can be distinguished from intracellular steroid-receptor complexes by agar electrophoresis at low temperature in neuraminidase-treated tissue extracts. With this method, the presence of progesterone receptor has been demonstrated in heavily plasma-protein-contaminated human uterus \"cytosol\", but not in human mammary carcinoma extracts. SHBG and \"basic\" receptors for estradiol and dihydrotestosterone in human uterus cytosol could also be assayed simultaneously.", "contents": "Differentiation between steroid hormone receptors CBG and SHBG in human target organ extracts by a single-step assay. The steroid complexes of (plasma) corticosteroid-binding globulin can be distinguished from intracellular steroid-receptor complexes by agar electrophoresis at low temperature in neuraminidase-treated tissue extracts. With this method, the presence of progesterone receptor has been demonstrated in heavily plasma-protein-contaminated human uterus \"cytosol\", but not in human mammary carcinoma extracts. SHBG and \"basic\" receptors for estradiol and dihydrotestosterone in human uterus cytosol could also be assayed simultaneously."} {"id": "PMID:173589", "title": "Testicular inhibition of fetal Mullerian ducts in vitro: effect of dibutyryl cyclic AMP.", "content": "The effect of dibutyryl cyclic AMP (dibutyryl cAMP) on Mullerian ducts of 141/2-day-old rat fetuses in vitro was investigated. Dibutyryl cAMP was unable to produce the typical regression of M\u00fcllerian ducts which is observed in vivo in male fetuses and in vitro with M\u00fcllerian ducts in the presence of testes. Effects of dibutyryl cAMP and theophylline on regeneration of M\u00fcllerian ducts induced by fetal testes were also investigated, and it was found that 10(-3) dibutyryl cAMP added to the culture medium prevented the normal regression. Lower concentrations and theophyline (10(-3)M) were ineffective. An effect of lower doses of dibutyryl cAMP was obtained only when theophylline was also present. Because pretreatment of testes with dibutyryl cAMP did not prevent the inhibiting action of testes on M\u00fcllerian ducts, it is concluded that an interaction between dibutyryl cAMP and the inhibiting factor at the level of the target organs must be considered.", "contents": "Testicular inhibition of fetal Mullerian ducts in vitro: effect of dibutyryl cyclic AMP. The effect of dibutyryl cyclic AMP (dibutyryl cAMP) on Mullerian ducts of 141/2-day-old rat fetuses in vitro was investigated. Dibutyryl cAMP was unable to produce the typical regression of M\u00fcllerian ducts which is observed in vivo in male fetuses and in vitro with M\u00fcllerian ducts in the presence of testes. Effects of dibutyryl cAMP and theophylline on regeneration of M\u00fcllerian ducts induced by fetal testes were also investigated, and it was found that 10(-3) dibutyryl cAMP added to the culture medium prevented the normal regression. Lower concentrations and theophyline (10(-3)M) were ineffective. An effect of lower doses of dibutyryl cAMP was obtained only when theophylline was also present. Because pretreatment of testes with dibutyryl cAMP did not prevent the inhibiting action of testes on M\u00fcllerian ducts, it is concluded that an interaction between dibutyryl cAMP and the inhibiting factor at the level of the target organs must be considered."} {"id": "PMID:173590", "title": "Oestrogen receptor in mammary gland cytosol of virgin, pregnant and lactating mice.", "content": "A macromolecular component binding 3H-labelled 17 beta-oestradiol in a specific manner and sedimenting in the 8-10-S region on sucrose gradient has been detected in the mammary gland cytosol of ovariectomized adult virgin mice. The dissociation constant of the macromolecule-oestradiol complex is 4.2 times 10(-10)M at 4 degrees C. The binding sites for 17beta-oestradiol of cytosol are 3.7 times 10(-14) mole/mg of protein. Incubation of cytosol with different enzymes suggests that the oestrogen-binding cytosol component is proteinaceous. The binding activity is destroyed by incubation at high temperatures and by some but not all SH-reagents tested. Competition studies show a specificity for oestrogens relative to other steroid hormones. The conclusion is that mammary gland cytosol of virgin mice contains oestradiol receptor. The receptor content does not increase in a specific manner during pregnancy and lactation but rather proportionally to total mammary gland protein.", "contents": "Oestrogen receptor in mammary gland cytosol of virgin, pregnant and lactating mice. A macromolecular component binding 3H-labelled 17 beta-oestradiol in a specific manner and sedimenting in the 8-10-S region on sucrose gradient has been detected in the mammary gland cytosol of ovariectomized adult virgin mice. The dissociation constant of the macromolecule-oestradiol complex is 4.2 times 10(-10)M at 4 degrees C. The binding sites for 17beta-oestradiol of cytosol are 3.7 times 10(-14) mole/mg of protein. Incubation of cytosol with different enzymes suggests that the oestrogen-binding cytosol component is proteinaceous. The binding activity is destroyed by incubation at high temperatures and by some but not all SH-reagents tested. Competition studies show a specificity for oestrogens relative to other steroid hormones. The conclusion is that mammary gland cytosol of virgin mice contains oestradiol receptor. The receptor content does not increase in a specific manner during pregnancy and lactation but rather proportionally to total mammary gland protein."} {"id": "PMID:173599", "title": "Infectivity studies of hepatitis A and B in non-human primates.", "content": "We have induced hepatitis A in marmosets of the subspecies Saguinus mystax following primary inoculation with human serum containing the MS-1 strain of hepatitis A virus (HAV) and in 3 further marmoset subpassages using infective marmoset serum from each preceding passage. In each passage acquisition of serum antibody against 17 nm virus-like particles recovered from acute illness stools of human volunteers who developed hepatitis following inoculation with the MS-1 strain of HAV, as well as from acute illness stools of hepatitis A cases from a common source epidemic of heaptitis A in Arizona could be demonstrated by immune electron microscopy (IEM). Particle-containing stool filtrates from the latter epidemic also induced hepatitis in chimpanzees after intravenous inoculation. Inoculation of partially purified particles from a single banding in CsCl2 has further resulted in the induction of hepatitis in S. mystax marmosets. We have successfully induced hepatitis in a series of chimpanzees inoculated with sera containing hepatitis B surface antigen (HBsAg) of varying subspecificities. Susceptibility appears universal in animals who are initially lacking in serum antibody (anti-HBs) and antibody induced following experimental infection is homologous in subspecificity to the subspecificities of the antigenic coat components of the HBsAg in the inoculum. Results of cross challenge experiments indicate that animals developing hepatitis following inoculation of HBsAg of one subspecificity set in the d/y-w/r system do not again develop hepatitis following inoculation with HBsAg of the alternate subspecificity set.", "contents": "Infectivity studies of hepatitis A and B in non-human primates. We have induced hepatitis A in marmosets of the subspecies Saguinus mystax following primary inoculation with human serum containing the MS-1 strain of hepatitis A virus (HAV) and in 3 further marmoset subpassages using infective marmoset serum from each preceding passage. In each passage acquisition of serum antibody against 17 nm virus-like particles recovered from acute illness stools of human volunteers who developed hepatitis following inoculation with the MS-1 strain of HAV, as well as from acute illness stools of hepatitis A cases from a common source epidemic of heaptitis A in Arizona could be demonstrated by immune electron microscopy (IEM). Particle-containing stool filtrates from the latter epidemic also induced hepatitis in chimpanzees after intravenous inoculation. Inoculation of partially purified particles from a single banding in CsCl2 has further resulted in the induction of hepatitis in S. mystax marmosets. We have successfully induced hepatitis in a series of chimpanzees inoculated with sera containing hepatitis B surface antigen (HBsAg) of varying subspecificities. Susceptibility appears universal in animals who are initially lacking in serum antibody (anti-HBs) and antibody induced following experimental infection is homologous in subspecificity to the subspecificities of the antigenic coat components of the HBsAg in the inoculum. Results of cross challenge experiments indicate that animals developing hepatitis following inoculation of HBsAg of one subspecificity set in the d/y-w/r system do not again develop hepatitis following inoculation with HBsAg of the alternate subspecificity set."} {"id": "PMID:173600", "title": "Immune adherence and complement-fixation tests for human hepatitis A. Diagnostic and epidemiologic investigations.", "content": "The reliable propagation of CR326 strain of human hepatitis A virus in Saguinus mystax marmosets has permitted the development of specific serum neutralization, complement-fixation (CF), and immune adherence (IA) assays for hepatitis A antigen and antibody. The CF and IA assays were made possible by the use of livers of CR326-infected marmosets as a source of hepatitis A antigen. All assays were shown to be specific for hepatitis A. Cases of hepatitis B did not show development of hepatitis A antibody. Hepatitis A antibody appeared following onset of illness, and, in the longest time period studied, has persisted for 7 years. Epidemiologic studies have been performed on several Costa Rican families with outbreaks of hepatitis, using the IA and CF assays. Also, several populations in the U.S.A. were studied. These indicated a high incidence of hepatitis A at an early age in Costa Rica and a relatively low incidence of hepatitis A antibody among adults in the U.S.A. It was shown that human immune globulin can be standardized for hepatitis A antibody content by the IA assay. Finally, the IA assay indicated probable hepatitis A antibody in uninoculated chimpanzees, grivet monkeys, and rhesus monkeys.", "contents": "Immune adherence and complement-fixation tests for human hepatitis A. Diagnostic and epidemiologic investigations. The reliable propagation of CR326 strain of human hepatitis A virus in Saguinus mystax marmosets has permitted the development of specific serum neutralization, complement-fixation (CF), and immune adherence (IA) assays for hepatitis A antigen and antibody. The CF and IA assays were made possible by the use of livers of CR326-infected marmosets as a source of hepatitis A antigen. All assays were shown to be specific for hepatitis A. Cases of hepatitis B did not show development of hepatitis A antibody. Hepatitis A antibody appeared following onset of illness, and, in the longest time period studied, has persisted for 7 years. Epidemiologic studies have been performed on several Costa Rican families with outbreaks of hepatitis, using the IA and CF assays. Also, several populations in the U.S.A. were studied. These indicated a high incidence of hepatitis A at an early age in Costa Rica and a relatively low incidence of hepatitis A antibody among adults in the U.S.A. It was shown that human immune globulin can be standardized for hepatitis A antibody content by the IA assay. Finally, the IA assay indicated probable hepatitis A antibody in uninoculated chimpanzees, grivet monkeys, and rhesus monkeys."} {"id": "PMID:173601", "title": "The mythology of various hepatitis A virus isolates.", "content": "Several types of viral hepatitis may exist. Hepatitis A (MS-1 type) can be transmitted to marmosets and chimpanzees. Virus-like particles, which may be parvo- or enteroviruses and which have been demonstrated in feces of this type of hepatitis, do not share cross-reacting antigens with hepatitis B but do cross-react with fecal hepatitis A antigen. Hepatitis A (GB type), which also does not cross-react with hepatitis B, is not antigenically identical with MS-1; it can be transmitted to marmosets and it may be similar to non-type A/non-type B post-transfusion hepatitis. Hepatitits B does not cross-react either with HA particles, the faecal hepatitis type A antigen or with the MS-1 or GB strains; it can be transmitted to chimpanzees and rhesus monkeys but not to marmosets.", "contents": "The mythology of various hepatitis A virus isolates. Several types of viral hepatitis may exist. Hepatitis A (MS-1 type) can be transmitted to marmosets and chimpanzees. Virus-like particles, which may be parvo- or enteroviruses and which have been demonstrated in feces of this type of hepatitis, do not share cross-reacting antigens with hepatitis B but do cross-react with fecal hepatitis A antigen. Hepatitis A (GB type), which also does not cross-react with hepatitis B, is not antigenically identical with MS-1; it can be transmitted to marmosets and it may be similar to non-type A/non-type B post-transfusion hepatitis. Hepatitits B does not cross-react either with HA particles, the faecal hepatitis type A antigen or with the MS-1 or GB strains; it can be transmitted to chimpanzees and rhesus monkeys but not to marmosets."} {"id": "PMID:173602", "title": "Virus-like particles in hepatitis A.", "content": "Distinctive 27 nm virus-like particles have been found by immune electron microscopy in faecal extracts obtained during the late incubation of naturally occurring hepatitis A infection. A variety of particles measuring 22 nm and 30 nm have also been observed. However, the predominance of the 27 nm particles suggests that these small cubic virus-like structures are closely associated with hepatitis A.", "contents": "Virus-like particles in hepatitis A. Distinctive 27 nm virus-like particles have been found by immune electron microscopy in faecal extracts obtained during the late incubation of naturally occurring hepatitis A infection. A variety of particles measuring 22 nm and 30 nm have also been observed. However, the predominance of the 27 nm particles suggests that these small cubic virus-like structures are closely associated with hepatitis A."} {"id": "PMID:173603", "title": "Characterization of CR326 human hepatitis A virus, a probable enterovirus.", "content": "CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 mmu spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, identical 27 mmu viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The buoyant density of the virus in CsCl was 1.34 and it was heat (60 degrees C), ether and acid stable but was destroyed by heat (100 degrees C), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.", "contents": "Characterization of CR326 human hepatitis A virus, a probable enterovirus. CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 mmu spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, identical 27 mmu viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The buoyant density of the virus in CsCl was 1.34 and it was heat (60 degrees C), ether and acid stable but was destroyed by heat (100 degrees C), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus."} {"id": "PMID:173604", "title": "Attempts to differential hepatitis B from hepatitis A infection by newly developed serological tests.", "content": "An immune Indian ink micro-agglutination method has been evolved for the detection of an antigen present in the blood associated with infectious hepatitis (called IHxAg). In previous studies 86% of serum samples taken from children with hepatitis A proved to be positive by this technique. Present studies were related to 239 adult in-patients with a clinical diagnosis of hepatitis A (123 cases) or hepatitis B (116 cases). Blood samples taken serially during the illness were tested for IHxAg, HBsAg and anti-HBsAg. The results were in accordance with the clinical diagnosis in 60% in contradiction in 30%, whilst all tests brought negative results in 10%. The clinical laboratory findings (SGPT, thymol turbidity) were more in harmony with our laboratory results than with the clinical diagnoses. Rheumatoid factor did not disturb the immune Indian ink reaction, labile serum proteins caused, however, non-specific reaction in 30% of serum samples. When durocytes were used instead of Indian ink the rate of false positive results dropped to 10%. Sera taken in convalescent phase from patients with IHx antigenemia in the acute phase of illness contained an antibody against IHxAg. A crude gammaglobulin preparation from a pool of convalescent sera gave a precipitation line in agarose gel with an antigen present in the fecal extract of children with hepatitis A. This precipitation line proved to contain virus-like particles with an approximate diameter of 25 nm when tested by electronmicroscopy. No precipitation could be seen when sera of the same patients were tested against the same gammaglobulin preparation.", "contents": "Attempts to differential hepatitis B from hepatitis A infection by newly developed serological tests. An immune Indian ink micro-agglutination method has been evolved for the detection of an antigen present in the blood associated with infectious hepatitis (called IHxAg). In previous studies 86% of serum samples taken from children with hepatitis A proved to be positive by this technique. Present studies were related to 239 adult in-patients with a clinical diagnosis of hepatitis A (123 cases) or hepatitis B (116 cases). Blood samples taken serially during the illness were tested for IHxAg, HBsAg and anti-HBsAg. The results were in accordance with the clinical diagnosis in 60% in contradiction in 30%, whilst all tests brought negative results in 10%. The clinical laboratory findings (SGPT, thymol turbidity) were more in harmony with our laboratory results than with the clinical diagnoses. Rheumatoid factor did not disturb the immune Indian ink reaction, labile serum proteins caused, however, non-specific reaction in 30% of serum samples. When durocytes were used instead of Indian ink the rate of false positive results dropped to 10%. Sera taken in convalescent phase from patients with IHx antigenemia in the acute phase of illness contained an antibody against IHxAg. A crude gammaglobulin preparation from a pool of convalescent sera gave a precipitation line in agarose gel with an antigen present in the fecal extract of children with hepatitis A. This precipitation line proved to contain virus-like particles with an approximate diameter of 25 nm when tested by electronmicroscopy. No precipitation could be seen when sera of the same patients were tested against the same gammaglobulin preparation."} {"id": "PMID:173605", "title": "Incorporation of 75Se-selenomethionine into human apoproteins. I. Characterization of specificity in very-low-density and low-density lipoproteins.", "content": "Characterization of specificity of incorporation of 75Se-selenomethionine into human apoproteins following in-vivo injection of the radioactive amino acid precursor is reported. Apoprotein fractionation was attained by serial ultracentrifugation, anhydrous partial delipidization, decyl sulfate solubilization with Sephadex G-150 gel filtration into polypeptide fractions, Sf-I, and Sf-II, for VLDL, and LDL subfractions. Similarity of the Sf-I fractions isolated from VLDL, LDL1, and LDL2 was defined by gel exclusion volume, disk-gel electrophoresis, immunodiffusion, and amino acid composition. Enrichment of the Sf-I fractions with 75Se-SM in VLDL and LDL subfractions was observed, suggesting a possible use for this isotopic method for the investigation of apoprotein metabolism.", "contents": "Incorporation of 75Se-selenomethionine into human apoproteins. I. Characterization of specificity in very-low-density and low-density lipoproteins. Characterization of specificity of incorporation of 75Se-selenomethionine into human apoproteins following in-vivo injection of the radioactive amino acid precursor is reported. Apoprotein fractionation was attained by serial ultracentrifugation, anhydrous partial delipidization, decyl sulfate solubilization with Sephadex G-150 gel filtration into polypeptide fractions, Sf-I, and Sf-II, for VLDL, and LDL subfractions. Similarity of the Sf-I fractions isolated from VLDL, LDL1, and LDL2 was defined by gel exclusion volume, disk-gel electrophoresis, immunodiffusion, and amino acid composition. Enrichment of the Sf-I fractions with 75Se-SM in VLDL and LDL subfractions was observed, suggesting a possible use for this isotopic method for the investigation of apoprotein metabolism."} {"id": "PMID:173606", "title": "Incorporation of 75Se-selenomethionine into human apoproteins. II. Characterization of metabolism of very-low-density and low-density lipoproteins in vivo and in vitro.", "content": "This investigation is designed to explore the potential role of apo VLDL as a precursor of a polypeptide component of human LDL. Attention was directed to the chromatography-defined Sf-I polypeptide fraction of apo VLDL, which has been previously shown to be immunologically and chemically indistinguishable from the major component of apoLDL.1-3 In VLDL isolated from bloow drawn within two hours following 75Se-SM injection, the Sf-I polypeptide fraction of apo VLDL was highly enriched with isotope, providing an appropriate preparation for in-vitro tracer studies. Conversion of 75Se-VLDL to 75Se-LDL occurred in vitro in the presence of normal plasma at 37 degrees C., and this conversion was augmented by post-heparin plasma. No conversion to HDL lipoproteins could be detected. Injection of heparin in vivo resulted in acute reciprocal changes in the radioactivity contained within serum apo VLDL and apoLDL. These findings suggest that a component of the Sf-I polypeptide fraction of apo VLDL can be metabolized into the apoprotein of LDL in man. Thus, the biochemical and immunologic similarities between the Sf-I fractions of apoVLDL and apoLDL may result from a physiologic \"precursor-product\" relationship between the apoprotein moieties of these two lipoprotein species. A method for further investigation of the metabolism of human apoprotein is suggested.", "contents": "Incorporation of 75Se-selenomethionine into human apoproteins. II. Characterization of metabolism of very-low-density and low-density lipoproteins in vivo and in vitro. This investigation is designed to explore the potential role of apo VLDL as a precursor of a polypeptide component of human LDL. Attention was directed to the chromatography-defined Sf-I polypeptide fraction of apo VLDL, which has been previously shown to be immunologically and chemically indistinguishable from the major component of apoLDL.1-3 In VLDL isolated from bloow drawn within two hours following 75Se-SM injection, the Sf-I polypeptide fraction of apo VLDL was highly enriched with isotope, providing an appropriate preparation for in-vitro tracer studies. Conversion of 75Se-VLDL to 75Se-LDL occurred in vitro in the presence of normal plasma at 37 degrees C., and this conversion was augmented by post-heparin plasma. No conversion to HDL lipoproteins could be detected. Injection of heparin in vivo resulted in acute reciprocal changes in the radioactivity contained within serum apo VLDL and apoLDL. These findings suggest that a component of the Sf-I polypeptide fraction of apo VLDL can be metabolized into the apoprotein of LDL in man. Thus, the biochemical and immunologic similarities between the Sf-I fractions of apoVLDL and apoLDL may result from a physiologic \"precursor-product\" relationship between the apoprotein moieties of these two lipoprotein species. A method for further investigation of the metabolism of human apoprotein is suggested."} {"id": "PMID:173609", "title": "The control of insulin receptors in the New Zealand obese mouse.", "content": "Insulin receptor concentrations in liver plasma membranes of New Zealand Obese (NZO) mice have been studied. When NZO mice were implanted with normal islets of Langerhans their blood glucose and plasma insulin declined. When the implanted islets were removed these changes were reversed and the mice reverted to their insulin resistant state. Changes were observed in the binding of 125I-insulin to liver plasma membranes of implanted NZO mice. Binding increased when the plasma insulin was decreased and conversely insulin binding decreased when the plasma insulin levels became elevated. The increased insulin binding was not accompanied by any changes in the affinity of NZO liver receptors for insulin.", "contents": "The control of insulin receptors in the New Zealand obese mouse. Insulin receptor concentrations in liver plasma membranes of New Zealand Obese (NZO) mice have been studied. When NZO mice were implanted with normal islets of Langerhans their blood glucose and plasma insulin declined. When the implanted islets were removed these changes were reversed and the mice reverted to their insulin resistant state. Changes were observed in the binding of 125I-insulin to liver plasma membranes of implanted NZO mice. Binding increased when the plasma insulin was decreased and conversely insulin binding decreased when the plasma insulin levels became elevated. The increased insulin binding was not accompanied by any changes in the affinity of NZO liver receptors for insulin."} {"id": "PMID:173610", "title": "Effect of methylxanthines on alloxan inhibition of insulin release.", "content": "Isloated rat islets were maintained in vitro in a perifusion system, exposed to alloxan (20 mg/100 ml) for 5 minutes in the presence of agents which affect cAMP metabolism and subsequently stimulated with glucose. The rate of insulin secretion was monitored throughout the period of perifusion. Exposure to alloxan alone produces complete inhibition of glucose-induced insulin release [18] whereas concomitant exposure to carreine and theophylline for this brief interval provided almost complete protection of the islets from the inhibitory action of alloxan. Glucagon, cAMP and CBcAMP did not protect the islets form alloxan. Pre-treatment of the islets with either theophylline or glucagon and DBcAMP did not provide protection. These findings indicate that the protective action of theophylline and carreine against alloxan is unrelated to the effect of these agents on cAMP metabolism in the beta cell.", "contents": "Effect of methylxanthines on alloxan inhibition of insulin release. Isloated rat islets were maintained in vitro in a perifusion system, exposed to alloxan (20 mg/100 ml) for 5 minutes in the presence of agents which affect cAMP metabolism and subsequently stimulated with glucose. The rate of insulin secretion was monitored throughout the period of perifusion. Exposure to alloxan alone produces complete inhibition of glucose-induced insulin release [18] whereas concomitant exposure to carreine and theophylline for this brief interval provided almost complete protection of the islets from the inhibitory action of alloxan. Glucagon, cAMP and CBcAMP did not protect the islets form alloxan. Pre-treatment of the islets with either theophylline or glucagon and DBcAMP did not provide protection. These findings indicate that the protective action of theophylline and carreine against alloxan is unrelated to the effect of these agents on cAMP metabolism in the beta cell."} {"id": "PMID:173611", "title": "Increased sensitivity of diabetic rat adipose tissue towards the lipolytic action of epinephrine.", "content": "Adipose tissue from streptozotocin-diabetic rats exhibits half-maximal lipolytic responses (FFA, glycerol release, increase in tissue FFA) to epinephrine at hormone concentrations 5-10 times lowere than those required for half-maximal stimulation of lipolysis in adipose tissue from normal rats. The lipolytic response to epinephrine also occurs more promptly and the antilipolytic effect of insulin in the presence of submaximal epinephrine conceptrations is much less pronounced than in normal tissue. In contrast, diabetic adipose tissue is less responsive to ACTH and glucagon than normal tissue. Half-maximal lipolytic responses are elicited by similar dibutyryl cyclic AMP concentrations in both tissues. Insulin treatment of diabetic rats during 24 hrs restores the lipolytic response of their adipose tissue to epinephrine to nearly normal. Our findings point to an abnormality of diabetic adipose tissue possibly related to the hypersensitivity of catecholamines encountered in denervated organs which are adrenergically innvervated. They are consistent with present concept of different hormone discriminators on the fat cell membrane and offer a further explanation for increased FFA mobilization in the diabetic state.", "contents": "Increased sensitivity of diabetic rat adipose tissue towards the lipolytic action of epinephrine. Adipose tissue from streptozotocin-diabetic rats exhibits half-maximal lipolytic responses (FFA, glycerol release, increase in tissue FFA) to epinephrine at hormone concentrations 5-10 times lowere than those required for half-maximal stimulation of lipolysis in adipose tissue from normal rats. The lipolytic response to epinephrine also occurs more promptly and the antilipolytic effect of insulin in the presence of submaximal epinephrine conceptrations is much less pronounced than in normal tissue. In contrast, diabetic adipose tissue is less responsive to ACTH and glucagon than normal tissue. Half-maximal lipolytic responses are elicited by similar dibutyryl cyclic AMP concentrations in both tissues. Insulin treatment of diabetic rats during 24 hrs restores the lipolytic response of their adipose tissue to epinephrine to nearly normal. Our findings point to an abnormality of diabetic adipose tissue possibly related to the hypersensitivity of catecholamines encountered in denervated organs which are adrenergically innvervated. They are consistent with present concept of different hormone discriminators on the fat cell membrane and offer a further explanation for increased FFA mobilization in the diabetic state."} {"id": "PMID:173612", "title": "Human islet cell adenoma: metabolic analysis of the patient and of tumor cells in monolayer culture.", "content": "Cell cultures were established from a benign pancreatic islet adenoma. Over 200 muU/culture/day immunoreactive insulin were found in culture media. Cultures with medium 199 released insulin for about 2 months; those with medium F12K were maintained for over 7 months, and have been successfully subcultured. Increasing culture medium glucose to 326 mg per 100 ml, alone or with leucine (10 mM) or theophylline (2 mM), failed to increase insulin release above baseline. Studies in the patient prior to surgery using oral glucose, leucine, beef meal, intravenous tolbutamide, and glucagon failed to increase plasma insulin and thus were consistent with cell culture responses. Extracts of tumor tissue contained 23% proinsulin-like material; high insulin containing samples of culture medium had 5% proinsulin and less than 40 pg glucagon/ml. Aldehyde fuchsin positive granulation was sparse in both cultured cells and the original tumor. These studies demonstrate long term viability, in monolayer culture, of cells derived from this islet cell adenoma, with retention of secretory characteristics consistent with data obtained prior to removal of the adenoma from the patient.", "contents": "Human islet cell adenoma: metabolic analysis of the patient and of tumor cells in monolayer culture. Cell cultures were established from a benign pancreatic islet adenoma. Over 200 muU/culture/day immunoreactive insulin were found in culture media. Cultures with medium 199 released insulin for about 2 months; those with medium F12K were maintained for over 7 months, and have been successfully subcultured. Increasing culture medium glucose to 326 mg per 100 ml, alone or with leucine (10 mM) or theophylline (2 mM), failed to increase insulin release above baseline. Studies in the patient prior to surgery using oral glucose, leucine, beef meal, intravenous tolbutamide, and glucagon failed to increase plasma insulin and thus were consistent with cell culture responses. Extracts of tumor tissue contained 23% proinsulin-like material; high insulin containing samples of culture medium had 5% proinsulin and less than 40 pg glucagon/ml. Aldehyde fuchsin positive granulation was sparse in both cultured cells and the original tumor. These studies demonstrate long term viability, in monolayer culture, of cells derived from this islet cell adenoma, with retention of secretory characteristics consistent with data obtained prior to removal of the adenoma from the patient."} {"id": "PMID:173613", "title": "Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release.", "content": "Microdissected pancreatic islets from non-inbred ob/ob-mice were cultured for 6 or 7 days in serum-free tissue culture medium 199. The insulin content of the islets decreased 60% during culture in 17 mM or 28 mM glucose and about 70% in the presence of 3.3 mM or 5.6 mM glucose. At the end of a culture period in high glucose, the sum of the insulin in the islet plus that in the culture medium was almost twice as high as the insulin content of fresh islets, indicating an active insulin biosynthesis. The maximal insulin response to glucose after culture in 17 mM or 28 mM glucose was about 40% of that in fresh islets; after culture in 3.3 mM glucose it was 10%. Half-maximal stimulation was observed at a glucose concentration of 5 mM for islets cultured with high glucose as compared to 9 mM for fresh islets. Like glucose, glibenclamide was a more effective insulin stimulator after culture with a high glucose concentration than with a low one. However, leucine-induced insulin release was not affected by the glucose concentration in the preceding culture medium. Whereas potentiation of glucose-stimulated release by arginine or dibutyryl-cAMP was independent of glucose concentration during the culture, theophylline released three times more insulin when the islets had been cultured with high glucose.", "contents": "Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release. Microdissected pancreatic islets from non-inbred ob/ob-mice were cultured for 6 or 7 days in serum-free tissue culture medium 199. The insulin content of the islets decreased 60% during culture in 17 mM or 28 mM glucose and about 70% in the presence of 3.3 mM or 5.6 mM glucose. At the end of a culture period in high glucose, the sum of the insulin in the islet plus that in the culture medium was almost twice as high as the insulin content of fresh islets, indicating an active insulin biosynthesis. The maximal insulin response to glucose after culture in 17 mM or 28 mM glucose was about 40% of that in fresh islets; after culture in 3.3 mM glucose it was 10%. Half-maximal stimulation was observed at a glucose concentration of 5 mM for islets cultured with high glucose as compared to 9 mM for fresh islets. Like glucose, glibenclamide was a more effective insulin stimulator after culture with a high glucose concentration than with a low one. However, leucine-induced insulin release was not affected by the glucose concentration in the preceding culture medium. Whereas potentiation of glucose-stimulated release by arginine or dibutyryl-cAMP was independent of glucose concentration during the culture, theophylline released three times more insulin when the islets had been cultured with high glucose."} {"id": "PMID:173615", "title": "Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones.", "content": "In the presence of 5 mM theophylline, secretin and vasoactive intestinal peptide (VIP) each increased cyclic adenosine 3':5'-monophosphate (cyclic AMP) in acinar cells isolated from guinea pig pancreas. Without theophylline, neither peptide altered cellular cyclic AMP. Glucagon, which is similar to secretin and VIP both in chemical structure and spectrum of biologic activities, neither stimulated cellular cyclic AMP nor inhibited the stimulation produced by secretin or by VIP. Other agents which were tested and found not to increase cellular cyclic AMP were cholecystokinin, carboxyl-terminal octapeptide of cholecystokinin, gastrin I, gastrin II, bovine pancreatic polypeptide, carbamylcholine, and prostaglandin E1. Neither carboxyl-terminal octapeptide nor gastrin I altered the stimulation of cellular cyclic AMP produced by secretin or VIP. With natural secretin a significant increase in cellular cyclic AMP could be detected at concentrations as low as 3 x 10(-10) M and maximal stimulation occurred at 10(-8) M. VIP was approximately 1% as potent as natural secretin and maximal concentrations of secretin plus VIP increased cellular cyclic AMP to the same value as was obtained with a maximal concentration of secretin alone.", "contents": "Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones. In the presence of 5 mM theophylline, secretin and vasoactive intestinal peptide (VIP) each increased cyclic adenosine 3':5'-monophosphate (cyclic AMP) in acinar cells isolated from guinea pig pancreas. Without theophylline, neither peptide altered cellular cyclic AMP. Glucagon, which is similar to secretin and VIP both in chemical structure and spectrum of biologic activities, neither stimulated cellular cyclic AMP nor inhibited the stimulation produced by secretin or by VIP. Other agents which were tested and found not to increase cellular cyclic AMP were cholecystokinin, carboxyl-terminal octapeptide of cholecystokinin, gastrin I, gastrin II, bovine pancreatic polypeptide, carbamylcholine, and prostaglandin E1. Neither carboxyl-terminal octapeptide nor gastrin I altered the stimulation of cellular cyclic AMP produced by secretin or VIP. With natural secretin a significant increase in cellular cyclic AMP could be detected at concentrations as low as 3 x 10(-10) M and maximal stimulation occurred at 10(-8) M. VIP was approximately 1% as potent as natural secretin and maximal concentrations of secretin plus VIP increased cellular cyclic AMP to the same value as was obtained with a maximal concentration of secretin alone."} {"id": "PMID:173616", "title": "Colonic blood flow in cat and man as analyzed by an inert gas washout technique.", "content": "An inert gas elimination technique for studying blood flow and flow distribution in the colon was developed on the cat and applied to patients during abdominal surgery. The method involves recording of the elimination of intra-arterially injected 85Kr from a colonic segment whereby the gamma- and beta-radiation of the tracer is registered simultaneously by a scintillation detector and Geiger-Muller tube, respectively. Total blood flow was determined from the recording of gamma-radioactivity using a modification of Zierler's formula, and muscularis blood flow as calculated according to Kety from the mono-exponential elimination recorded by the Geiger-Muller tube. The relative weights of the muscularis and mucosa-submucosa were determined from dissections or histological sections. With these weights and total and muscularis blood flows, flow in the mucosa-submucosa was calculated. Total colonic blood flow was 18 +/- 2 ml per min and 100 g of colonic tissue (mean +/- SE; n = 21). In the muscularis layer blood flow amounted to 11 +/- 1 ml per min and 100 g of muscularis tissue (n = 12), and flow in the mucosa-submucosa was calculated to be 28 +/- 5 ml per min and 100 g of mucosal-submucosal tissue. A major fraction (66 +/- 6%) of total blood flow was distributed to the mucosa-submucosa. As total colonic blood flow was enhanced the increase in flow was diverted only to the mucosa-submucosa. The feline and human large bowel exhibited great qualitative and quantitative circulatory similarities.", "contents": "Colonic blood flow in cat and man as analyzed by an inert gas washout technique. An inert gas elimination technique for studying blood flow and flow distribution in the colon was developed on the cat and applied to patients during abdominal surgery. The method involves recording of the elimination of intra-arterially injected 85Kr from a colonic segment whereby the gamma- and beta-radiation of the tracer is registered simultaneously by a scintillation detector and Geiger-Muller tube, respectively. Total blood flow was determined from the recording of gamma-radioactivity using a modification of Zierler's formula, and muscularis blood flow as calculated according to Kety from the mono-exponential elimination recorded by the Geiger-Muller tube. The relative weights of the muscularis and mucosa-submucosa were determined from dissections or histological sections. With these weights and total and muscularis blood flows, flow in the mucosa-submucosa was calculated. Total colonic blood flow was 18 +/- 2 ml per min and 100 g of colonic tissue (mean +/- SE; n = 21). In the muscularis layer blood flow amounted to 11 +/- 1 ml per min and 100 g of muscularis tissue (n = 12), and flow in the mucosa-submucosa was calculated to be 28 +/- 5 ml per min and 100 g of mucosal-submucosal tissue. A major fraction (66 +/- 6%) of total blood flow was distributed to the mucosa-submucosa. As total colonic blood flow was enhanced the increase in flow was diverted only to the mucosa-submucosa. The feline and human large bowel exhibited great qualitative and quantitative circulatory similarities."} {"id": "PMID:173617", "title": "Blood flow in the small intestine of cat and man as analyzed by an inert gas washout technique.", "content": "Using a recently developed 85Kr-elimination technique, blood flow and flow distribution of the human small intestine have been investigated in patients during abdominal surgery. Total intestinal blood flow was estimated to be 38 +/- 4 ml per min and 100 g of intestinal tissue (mean +/- SE: n = 19), jejunal blood flow being slightly higher than ileal. In 14 of these patients muscularis blood flow was determined to be 21 +/- 2 ml per min and 100 g of muscularis tissue and mucosal-submucosal blood flow was calculated to be 51 +/- 6 ml per min and 100 g of mucosal-submucosal tissue. Seventy-five +/- 3% of total blood flow was distributed to the mucosa-submucosa and the remaining 25 +/- 3% to the muscularis. It was demonstrated that an increasing fraction of flow was diverted to the mucosa-submucosa with enhanced total intestinal blood flow. The human gut exhibited great qualitative and quantitative circulatory similarities with the feline small intestine.", "contents": "Blood flow in the small intestine of cat and man as analyzed by an inert gas washout technique. Using a recently developed 85Kr-elimination technique, blood flow and flow distribution of the human small intestine have been investigated in patients during abdominal surgery. Total intestinal blood flow was estimated to be 38 +/- 4 ml per min and 100 g of intestinal tissue (mean +/- SE: n = 19), jejunal blood flow being slightly higher than ileal. In 14 of these patients muscularis blood flow was determined to be 21 +/- 2 ml per min and 100 g of muscularis tissue and mucosal-submucosal blood flow was calculated to be 51 +/- 6 ml per min and 100 g of mucosal-submucosal tissue. Seventy-five +/- 3% of total blood flow was distributed to the mucosa-submucosa and the remaining 25 +/- 3% to the muscularis. It was demonstrated that an increasing fraction of flow was diverted to the mucosa-submucosa with enhanced total intestinal blood flow. The human gut exhibited great qualitative and quantitative circulatory similarities with the feline small intestine."} {"id": "PMID:173614", "title": "[Differential ultrastructural elements in human cytomegalovirus and Herpes simplex virus replication in cultures of human cells].", "content": "Differential ultrastructural features in the replicative cycle between a strain of human cytomegalovirus (CMV) and two strains (types 1 and 2) of herpes simplex virus (HSV) have been studied by electron microscopy. Either on the same or different host cell system four differential aspects have been constantly observed: a) presence in CMV infected cells of a large nuclear inclusion, lacking in HSV infected cells; b) envelopment of CMV capsids by microvescicular systems near the nuclear membrane, whereas HSV (types 1 and 2) takes envelope from the inner lamina of the nuclear membrane; c) presence in the cytoplasm of CMV infected cells of homogeneous dense material and dense microbodies, lacking in HSV infected cells; d) in extracellular space homogenous dense microbodies are present only in CMV infected cell cultures. Diagnostic usefulness of the above reported ultrastructural differences and their meaning on the basis of most recent data of the literature are discussed, with special concern to envelopment of two viruses and to the nature of homogeneous dense material observed in CMV infected cells.", "contents": "[Differential ultrastructural elements in human cytomegalovirus and Herpes simplex virus replication in cultures of human cells]. Differential ultrastructural features in the replicative cycle between a strain of human cytomegalovirus (CMV) and two strains (types 1 and 2) of herpes simplex virus (HSV) have been studied by electron microscopy. Either on the same or different host cell system four differential aspects have been constantly observed: a) presence in CMV infected cells of a large nuclear inclusion, lacking in HSV infected cells; b) envelopment of CMV capsids by microvescicular systems near the nuclear membrane, whereas HSV (types 1 and 2) takes envelope from the inner lamina of the nuclear membrane; c) presence in the cytoplasm of CMV infected cells of homogeneous dense material and dense microbodies, lacking in HSV infected cells; d) in extracellular space homogenous dense microbodies are present only in CMV infected cell cultures. Diagnostic usefulness of the above reported ultrastructural differences and their meaning on the basis of most recent data of the literature are discussed, with special concern to envelopment of two viruses and to the nature of homogeneous dense material observed in CMV infected cells."} {"id": "PMID:173620", "title": "A deletion map of cyc1 mutants and its correspondence to mutationally altered iso-1-cytochromes c of yeast.", "content": "Mutants arising spontaneously from sporulated cultures of certain strains of yeast, Saccharomyces cerevisiae, contained deletions of the CYC1 gene which controls the primary structure of iso-1-cytochrome c. At least 60 different kinds of deletions were uncovered among the 104 deletions examined and these ranged in length from those encompassing only two adjacent point mutants to those encompassing at least the entire CYC1 gene. X-ray-induced recombination rates of crosses involving these deletions and cyc1 point mutants resulted in the assignment of 211 point mutants to 47 mutational sites and made it possible to unambiguously order 40 of these 47 sites. Except for one mutant, cyc1-15, there was a strict colinear relationship between the deletion map and the positions of 13 sites that were previously determined by amino acid alterations in iso-1-cytochromes c from intragenic revertants.", "contents": "A deletion map of cyc1 mutants and its correspondence to mutationally altered iso-1-cytochromes c of yeast. Mutants arising spontaneously from sporulated cultures of certain strains of yeast, Saccharomyces cerevisiae, contained deletions of the CYC1 gene which controls the primary structure of iso-1-cytochrome c. At least 60 different kinds of deletions were uncovered among the 104 deletions examined and these ranged in length from those encompassing only two adjacent point mutants to those encompassing at least the entire CYC1 gene. X-ray-induced recombination rates of crosses involving these deletions and cyc1 point mutants resulted in the assignment of 211 point mutants to 47 mutational sites and made it possible to unambiguously order 40 of these 47 sites. Except for one mutant, cyc1-15, there was a strict colinear relationship between the deletion map and the positions of 13 sites that were previously determined by amino acid alterations in iso-1-cytochromes c from intragenic revertants."} {"id": "PMID:173621", "title": "Lipid deficiencies, leukocytosis, brittle skin--a lethal syndrome caused by a recessive mutation, edematous (oed), in the mouse.", "content": "A new neonatal lethal mutation in the mouse with pleiotropic effects, edematous (oed), arose spontaneoutosomal recessive mode of inheritance. The external phenotypic characteristics include a generally bloated appearance, shiny celophane-like skin, and distal hematomata of the extremities. Internally, no gross or histological abnormalities could be identified, with the exception of a striking leukocytosis. Biochemical analysis revealed a severe disturbance of lipid metabolism. Deficiencies in the VLDL, LDL, and the HDL lipoprotein fractions have been found in the mutant plasma. In addition, all serum lipids are markedly decreased. However, in the mutant liver, only triglycerides are significantly decreased; total liver cholesterol and phospholipid values are within normal limits. The primary biochemical defect as well as the causal relationship between the striking abnormalities of lipid metabolism and those of skin and blood are unknown at this time.", "contents": "Lipid deficiencies, leukocytosis, brittle skin--a lethal syndrome caused by a recessive mutation, edematous (oed), in the mouse. A new neonatal lethal mutation in the mouse with pleiotropic effects, edematous (oed), arose spontaneoutosomal recessive mode of inheritance. The external phenotypic characteristics include a generally bloated appearance, shiny celophane-like skin, and distal hematomata of the extremities. Internally, no gross or histological abnormalities could be identified, with the exception of a striking leukocytosis. Biochemical analysis revealed a severe disturbance of lipid metabolism. Deficiencies in the VLDL, LDL, and the HDL lipoprotein fractions have been found in the mutant plasma. In addition, all serum lipids are markedly decreased. However, in the mutant liver, only triglycerides are significantly decreased; total liver cholesterol and phospholipid values are within normal limits. The primary biochemical defect as well as the causal relationship between the striking abnormalities of lipid metabolism and those of skin and blood are unknown at this time."} {"id": "PMID:173623", "title": "Interrelationships of dental maturity, skeletal maturity, height and weight from age 4 to 14 years.", "content": "The correlations of dental mineralization stages, skeletal mineralization, body-height and weight were determined for each year between age 4 and 14 for 121 boys and 111 girls of the serial experimental group of the Burlington Growth Centre. Dental development related more strongly to morphological development than to skeletal development in both sexes, and skeletal age was more strongly related to morphological age than to dental stage. The relationship of individual teeth to skeletal age, height and weight were different but consistent in a sex-specific pattern. In males, both skeletal mineralization and dental mineralization, particularly of the first molars, were more closely related to height than to weight. In the females, skeletal and dental mineralization, especially of the second molars, were more closely related to weight from age 7 than to height. These relationships were significant in both pre-adolescent and adolescent years. In both these periods, skeletal age and body size related most strongly to late stages of tooth formation. Hence, from an early age, the stages of dental, skeletal and morphological maturation were significantly interrelated in a pattern that was specific for individual teeth and for sex.", "contents": "Interrelationships of dental maturity, skeletal maturity, height and weight from age 4 to 14 years. The correlations of dental mineralization stages, skeletal mineralization, body-height and weight were determined for each year between age 4 and 14 for 121 boys and 111 girls of the serial experimental group of the Burlington Growth Centre. Dental development related more strongly to morphological development than to skeletal development in both sexes, and skeletal age was more strongly related to morphological age than to dental stage. The relationship of individual teeth to skeletal age, height and weight were different but consistent in a sex-specific pattern. In males, both skeletal mineralization and dental mineralization, particularly of the first molars, were more closely related to height than to weight. In the females, skeletal and dental mineralization, especially of the second molars, were more closely related to weight from age 7 than to height. These relationships were significant in both pre-adolescent and adolescent years. In both these periods, skeletal age and body size related most strongly to late stages of tooth formation. Hence, from an early age, the stages of dental, skeletal and morphological maturation were significantly interrelated in a pattern that was specific for individual teeth and for sex."} {"id": "PMID:173624", "title": "Stimulation of water and sodium secretion and inhibition of glucose absorption from the rat jejunum during intraarterial infusions of prostglandins.", "content": "The effect of prostaglandins, isoprenaline and dibutyryl cyclic adenosine monophosphate (dibut cAMP) on the net transfer of water and Na+ and glucose absorption have been studied in the anaesthetized rat. The lumen of the jejunum was recirculated with a solution of normal saline containing D (+) glucose and phenosulphonphthalein. The superior mesenteric artery was perfused extracorporeally and drugs were infused into the arterial blood. Prostaglandin E1 (PGE1) at infusion rates of 2-5 X 10(-9) and 10(-8) mol/min induced a net secretion of water and Na+ which was significantly different from the infused control mean. Both water and Na+ secretion were dose-related. PGE1 induced slight but significant inhibition of glucose absorption at 10(-8) mol/min. This could either be a direct effect or secondary to solvent drag. PGE2 (2-5 X 10(-9) mol/min) and PGF2alpha (8 X 10(-9) mol/min) induced water and Na+ secretion, and inhibited glucose absorption but not significantly. Isoprenaline (10(-9) mol/min) and dibut cAMP (8 X 10(-9) mol/min) did not alter water, Na+ or glucose absorption.", "contents": "Stimulation of water and sodium secretion and inhibition of glucose absorption from the rat jejunum during intraarterial infusions of prostglandins. The effect of prostaglandins, isoprenaline and dibutyryl cyclic adenosine monophosphate (dibut cAMP) on the net transfer of water and Na+ and glucose absorption have been studied in the anaesthetized rat. The lumen of the jejunum was recirculated with a solution of normal saline containing D (+) glucose and phenosulphonphthalein. The superior mesenteric artery was perfused extracorporeally and drugs were infused into the arterial blood. Prostaglandin E1 (PGE1) at infusion rates of 2-5 X 10(-9) and 10(-8) mol/min induced a net secretion of water and Na+ which was significantly different from the infused control mean. Both water and Na+ secretion were dose-related. PGE1 induced slight but significant inhibition of glucose absorption at 10(-8) mol/min. This could either be a direct effect or secondary to solvent drag. PGE2 (2-5 X 10(-9) mol/min) and PGF2alpha (8 X 10(-9) mol/min) induced water and Na+ secretion, and inhibited glucose absorption but not significantly. Isoprenaline (10(-9) mol/min) and dibut cAMP (8 X 10(-9) mol/min) did not alter water, Na+ or glucose absorption."} {"id": "PMID:173635", "title": "Oxidative enzymes in the development of Fasciola hepatica L. IV. The activity of oxidases and dehydrogenases in redia.", "content": "The object of the study was to investigate the occurrence and localization of oxidative enzymes in the redia -- the third larval stage of Fasciola hepatica L. The author detected cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases (diaphorases), as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde phosphate, glucose-6-phosphate, 6-phosphogluconate, beta-hydroxybutyrate, L-glutamate, and alcohol dehydrogenases. The presence and localization of the enzymes in various periods of development of the redia were detected with histochemical methods. Out of the studied oxidases and dehydrogenases only cytochrome oxidase was found to be absent from the stages of young rediae. It was ascertained that the redia uses all three paths of release of energy i.e. the glycolytic, Krebs, and pentose cycles, glycolysis being presumably the principal mode of energy production.", "contents": "Oxidative enzymes in the development of Fasciola hepatica L. IV. The activity of oxidases and dehydrogenases in redia. The object of the study was to investigate the occurrence and localization of oxidative enzymes in the redia -- the third larval stage of Fasciola hepatica L. The author detected cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases (diaphorases), as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde phosphate, glucose-6-phosphate, 6-phosphogluconate, beta-hydroxybutyrate, L-glutamate, and alcohol dehydrogenases. The presence and localization of the enzymes in various periods of development of the redia were detected with histochemical methods. Out of the studied oxidases and dehydrogenases only cytochrome oxidase was found to be absent from the stages of young rediae. It was ascertained that the redia uses all three paths of release of energy i.e. the glycolytic, Krebs, and pentose cycles, glycolysis being presumably the principal mode of energy production."} {"id": "PMID:173636", "title": "Oxidative enzymes in the development of Fasciola hepatica L. V. Activity of oxidases and dehydrogenases in the Cercaria and Metacercaria.", "content": "The object of the study was the investigation of the occurrence and localization of oxidative enzymes in the 4th and 5th larval stages of the liver fluke, i. e. in the cercaria and metacercaria. The following enzymes were detected: cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases/diaphorases) as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde phosphate, glucose-6-phosphate, 6-phosphogluconate, beta-hydroxybutyrate, L-glutamate and alcohol dehydrogenases. The occurrence and localization of the enzymes were investigated histochemically in the cercaria still unreleased from the snail tissues, in the free natatorial cercaria, and in the encysted specimen, i.e. metacercaria. Among the enzymes studied only peroxidase was found to be absent from the cercaria and metacercaria, the latter larva being deprived of alcohol and L-glutamate dehydrogenases as well. The aerobic path, i.e. the Krebs cycle, was ascertained as the principal mode of obtaining energy in the free natatorial cercaria and metacercaria, and glycolysis as the main energy path for the undetached larva. The analysis of the above-mentioned oxidative enzymes was the basis for the description, within the available range, of the function and metabolism of individual organs of cercaria in different periods of its development. In the recapitulation the author discusses the effect of the parasitic way of life of the larval forms of Fasciola hepatica on their energy metabolism.", "contents": "Oxidative enzymes in the development of Fasciola hepatica L. V. Activity of oxidases and dehydrogenases in the Cercaria and Metacercaria. The object of the study was the investigation of the occurrence and localization of oxidative enzymes in the 4th and 5th larval stages of the liver fluke, i. e. in the cercaria and metacercaria. The following enzymes were detected: cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases/diaphorases) as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde phosphate, glucose-6-phosphate, 6-phosphogluconate, beta-hydroxybutyrate, L-glutamate and alcohol dehydrogenases. The occurrence and localization of the enzymes were investigated histochemically in the cercaria still unreleased from the snail tissues, in the free natatorial cercaria, and in the encysted specimen, i.e. metacercaria. Among the enzymes studied only peroxidase was found to be absent from the cercaria and metacercaria, the latter larva being deprived of alcohol and L-glutamate dehydrogenases as well. The aerobic path, i.e. the Krebs cycle, was ascertained as the principal mode of obtaining energy in the free natatorial cercaria and metacercaria, and glycolysis as the main energy path for the undetached larva. The analysis of the above-mentioned oxidative enzymes was the basis for the description, within the available range, of the function and metabolism of individual organs of cercaria in different periods of its development. In the recapitulation the author discusses the effect of the parasitic way of life of the larval forms of Fasciola hepatica on their energy metabolism."} {"id": "PMID:173637", "title": "Specific and non-specific phosphatases in the miracidium of Fasciola hepatica L.", "content": "Localization and activities of alkaline phosphatase, ATPase, 5-nucleotidase, glucose-6-phosphatase, thiamine pyrophosphatase and nucleoside diphosphatase were studied in the miracidium of Fasciola hepatica L. Except for nucleoside diphosphatase whose activity in the miracidium was not observed, all the enzymes were most active in the archenteron, protonephridia and nerve ganglion. This localization of the reaction intensity allows the inference that the three organs mentioned are sites of both intense carbohydrate metabolism and lively active transport. The role of phosphatases in carbohydrate metabolism is discussed.", "contents": "Specific and non-specific phosphatases in the miracidium of Fasciola hepatica L. Localization and activities of alkaline phosphatase, ATPase, 5-nucleotidase, glucose-6-phosphatase, thiamine pyrophosphatase and nucleoside diphosphatase were studied in the miracidium of Fasciola hepatica L. Except for nucleoside diphosphatase whose activity in the miracidium was not observed, all the enzymes were most active in the archenteron, protonephridia and nerve ganglion. This localization of the reaction intensity allows the inference that the three organs mentioned are sites of both intense carbohydrate metabolism and lively active transport. The role of phosphatases in carbohydrate metabolism is discussed."} {"id": "PMID:173638", "title": "[The angiographic appearances of liver haemangiomas (author's transl)].", "content": "Thirteen cases of cavernous haemangiomas of the liver are described, and the clinical features, diagnosis and treatment are discussed. The purpose of this paper is to show the value of selective coeliac angiography in the differential diagnosis. The most important angiographic findings in cavernous haemangiomas of the liver are: supplying arteries of normal width, prolonged stasis of the contrast medium producing the appearance of spotty contrast depots, frequently, sharp delineation of the tumours; no A-V fistulae and no tumour vessels. Other hypervascular liver tumours must be distinguished from these, particularly hepatocellular carcinomas and sarcomas, as well as the rare haemangioendotheliomas.", "contents": "[The angiographic appearances of liver haemangiomas (author's transl)]. Thirteen cases of cavernous haemangiomas of the liver are described, and the clinical features, diagnosis and treatment are discussed. The purpose of this paper is to show the value of selective coeliac angiography in the differential diagnosis. The most important angiographic findings in cavernous haemangiomas of the liver are: supplying arteries of normal width, prolonged stasis of the contrast medium producing the appearance of spotty contrast depots, frequently, sharp delineation of the tumours; no A-V fistulae and no tumour vessels. Other hypervascular liver tumours must be distinguished from these, particularly hepatocellular carcinomas and sarcomas, as well as the rare haemangioendotheliomas."} {"id": "PMID:173639", "title": "[Angiographic findings in juvenile angiofibroma of the nasopharynx (author's transl)].", "content": "Juvenile angiofibroma of the nasopharynx has a specific tendency to grow through anatomical fissures and foramina with invasion of the surroundings. Angiography by selective techniques, detail angiography and the use of subtraction permits accurate delineation of the tumour and of its vascular supply. The angiographic appearances are highly characteristic and equal in value to a histological diagnosis. Consequently a possibly difficult biopsy can be avoided and radical surgery carried out. As a result, the recurrence rate can be reduced. Post-operative control and the demonstration of recurrences is also possible with angiography.", "contents": "[Angiographic findings in juvenile angiofibroma of the nasopharynx (author's transl)]. Juvenile angiofibroma of the nasopharynx has a specific tendency to grow through anatomical fissures and foramina with invasion of the surroundings. Angiography by selective techniques, detail angiography and the use of subtraction permits accurate delineation of the tumour and of its vascular supply. The angiographic appearances are highly characteristic and equal in value to a histological diagnosis. Consequently a possibly difficult biopsy can be avoided and radical surgery carried out. As a result, the recurrence rate can be reduced. Post-operative control and the demonstration of recurrences is also possible with angiography."} {"id": "PMID:173641", "title": "Epithelial basement membrane of bovine renal tubuli. Isolation and analysis of the carbohydrate chains.", "content": "The carbohydrate chains present in the tubular basement membrane of bovine kidney were studied. Digestion with collagenase followed with pronase resulted in a complete solubilization of the basement membrane. The different glycopeptides were purified by gel filtration and ion-exchange chromatography. Two kinds of carbohydrate chains could be characterized: oligosaccharides composed of glucosamine, mannose, galactose, fucose and sialic acid, and glucosylgalactose disaccharides. A very small portion of the oligosaccharide chains (ca. 4%) appeared to be free of sialic acid. The bulk of these chains contained sialic acid and fucose, although in small amounts. Only traces of galactosamine were found.", "contents": "Epithelial basement membrane of bovine renal tubuli. Isolation and analysis of the carbohydrate chains. The carbohydrate chains present in the tubular basement membrane of bovine kidney were studied. Digestion with collagenase followed with pronase resulted in a complete solubilization of the basement membrane. The different glycopeptides were purified by gel filtration and ion-exchange chromatography. Two kinds of carbohydrate chains could be characterized: oligosaccharides composed of glucosamine, mannose, galactose, fucose and sialic acid, and glucosylgalactose disaccharides. A very small portion of the oligosaccharide chains (ca. 4%) appeared to be free of sialic acid. The bulk of these chains contained sialic acid and fucose, although in small amounts. Only traces of galactosamine were found."} {"id": "PMID:173642", "title": "[Studies on the metabolism of oestrone and oestradiol-17 beta in the liver of minipigs of different ages and sexes (author's transl)].", "content": "After incubation of [4-14C]oestrone (E1) with liver slices from minipigs, the ether-soluble fraction contained [4-14C]oestradiol-17 beta (E2). In the protein-bound fractions, only polar metabolites were found, whereas in the water-soluble fraction the 3-monoglucuronide of oestriol (E1) was the preferred conjugate. When E2 was used as a substrate, E1 was present as main metabolite in the ether-soluble fraction. The radioactive metabolites in the protein-bound and water-soluble fractions were similar to those in the experiments with E1. The metabolism of E1 and E2 was dependent on age. Thus, the rate of conversion of oestrogens was greater in liver tissue of infertile male animals than in fertile males. In contrast, the two steroids were metabolised more rapidly in liver of fertile female minipigs than in infertile female animals. In fertile animals, the metabolic pattern of oestrogens in the ether-soluble, the protein-bound and the water-soluble fractions showed sex dependence: In females, E1 and E2 were metabolised to a greater extent by liver slices than in males. On the other hand, in experiments with male minipigs, E3-3-monoglucuronide was the only metabolite in the water-soluble fraction, whereas liver slices of female animals not only form E3-3-monoglucuronide, but also the 3-glucuronides of E1 and E2. The results described here show that, in liver tissue of minipigs, the oxidoreduction of E2 and E1 is the predominant reaction; in contrast to human liver, hydroxylation reactions play only a minor role. It may be concluded that there are differences in the metabolism of steroid hormones in man and minipig.", "contents": "[Studies on the metabolism of oestrone and oestradiol-17 beta in the liver of minipigs of different ages and sexes (author's transl)]. After incubation of [4-14C]oestrone (E1) with liver slices from minipigs, the ether-soluble fraction contained [4-14C]oestradiol-17 beta (E2). In the protein-bound fractions, only polar metabolites were found, whereas in the water-soluble fraction the 3-monoglucuronide of oestriol (E1) was the preferred conjugate. When E2 was used as a substrate, E1 was present as main metabolite in the ether-soluble fraction. The radioactive metabolites in the protein-bound and water-soluble fractions were similar to those in the experiments with E1. The metabolism of E1 and E2 was dependent on age. Thus, the rate of conversion of oestrogens was greater in liver tissue of infertile male animals than in fertile males. In contrast, the two steroids were metabolised more rapidly in liver of fertile female minipigs than in infertile female animals. In fertile animals, the metabolic pattern of oestrogens in the ether-soluble, the protein-bound and the water-soluble fractions showed sex dependence: In females, E1 and E2 were metabolised to a greater extent by liver slices than in males. On the other hand, in experiments with male minipigs, E3-3-monoglucuronide was the only metabolite in the water-soluble fraction, whereas liver slices of female animals not only form E3-3-monoglucuronide, but also the 3-glucuronides of E1 and E2. The results described here show that, in liver tissue of minipigs, the oxidoreduction of E2 and E1 is the predominant reaction; in contrast to human liver, hydroxylation reactions play only a minor role. It may be concluded that there are differences in the metabolism of steroid hormones in man and minipig."} {"id": "PMID:173643", "title": "[Studies on the metabolism of oestrone and oestradiol-17 beta in the kidneys of minipigs of different ages and sexes (author's transl)].", "content": "After incubation of [4-14C]oestrone (E1) with kidney cortex slices of minipigs, [4-14C]oestradiol-17 beta (E2) and small amounts of a polar metabolite were detected in the ether-soluble fraction. E1, E2 and polar metabolites were found in the protein-bound fraction. The water-soluble fraction contained E1-3-glucuronide (80% of total glucuronides), E2-3-glucuronide and trace amounts of the 3-monoglucuronide of oestriol (E3). When E2 was used as substrate, the main product formed was E1; it was detected in both the ether-soluble and protein-bound fractions. E1-3-Glucuronide was the main metabolite in the water-soluble fraction, which also contained some E2-3-Glucuronide. In male minipigs, the mast, the rate of conversion of E1 and E2 as well as the formation of glucuronides were significantly greater in fertile females than in infertile females. Whereas no sex difference was observed in the metabolism of oestrogens in kidneys of infertile minipigs, the rate of oxidoreduction and glucuronidation was more pronounced in fertile female animals than in the corresponding males. The present results suggest that, in the kidneys of minipigs, the ratio of E1 to E2 is shifted towards the former; furthermore, by a comparatively rapid metabolism of the oestrogenic hormone, the renal tissue contributes to the maintenance of hormonal equilibrium.", "contents": "[Studies on the metabolism of oestrone and oestradiol-17 beta in the kidneys of minipigs of different ages and sexes (author's transl)]. After incubation of [4-14C]oestrone (E1) with kidney cortex slices of minipigs, [4-14C]oestradiol-17 beta (E2) and small amounts of a polar metabolite were detected in the ether-soluble fraction. E1, E2 and polar metabolites were found in the protein-bound fraction. The water-soluble fraction contained E1-3-glucuronide (80% of total glucuronides), E2-3-glucuronide and trace amounts of the 3-monoglucuronide of oestriol (E3). When E2 was used as substrate, the main product formed was E1; it was detected in both the ether-soluble and protein-bound fractions. E1-3-Glucuronide was the main metabolite in the water-soluble fraction, which also contained some E2-3-Glucuronide. In male minipigs, the mast, the rate of conversion of E1 and E2 as well as the formation of glucuronides were significantly greater in fertile females than in infertile females. Whereas no sex difference was observed in the metabolism of oestrogens in kidneys of infertile minipigs, the rate of oxidoreduction and glucuronidation was more pronounced in fertile female animals than in the corresponding males. The present results suggest that, in the kidneys of minipigs, the ratio of E1 to E2 is shifted towards the former; furthermore, by a comparatively rapid metabolism of the oestrogenic hormone, the renal tissue contributes to the maintenance of hormonal equilibrium."} {"id": "PMID:173645", "title": "Psychiatric liaison with private facilities caring for discharged patients.", "content": "Motivated by concern about the fate of psychiatric hospital patients after discharge to the community, a community mental health center decided to send a psychiatrist into the community to establish liaison with private-care facilities and to determine the needs of such discharged patients. As a result of the psychiatrist's efforts, owners of the area's private-care facilities acquired a better understanding of the needs of their residents and learned where they could turn for help in caring for discharge psychiatric patients. A study of one board-and-care facility revealed a marked decrease in the use of the center's emergency service and in the number of hospital admissions after one year of this extended service.", "contents": "Psychiatric liaison with private facilities caring for discharged patients. Motivated by concern about the fate of psychiatric hospital patients after discharge to the community, a community mental health center decided to send a psychiatrist into the community to establish liaison with private-care facilities and to determine the needs of such discharged patients. As a result of the psychiatrist's efforts, owners of the area's private-care facilities acquired a better understanding of the needs of their residents and learned where they could turn for help in caring for discharge psychiatric patients. A study of one board-and-care facility revealed a marked decrease in the use of the center's emergency service and in the number of hospital admissions after one year of this extended service."} {"id": "PMID:173647", "title": "[Quantitative and virus specific serum IgM detection in newborns (author's transl)].", "content": "Serum IgM concentration was determined in umbilical cord blood samples from 1000 newborns. 34 cases presenting elevated IgM values (greater than or equal to 30 mg%) were tested for virus specific IgM antibodies. We could demonstrate such virus specific IgM antibodies against Cytomegalovirus (4), against Rubella, Influenza A and Influenza B (2 each) and against Coxsackie virus (1). The quantitation of IgM in blood samples of child bearing women showed no elevated values compared to those of non-pregnant women of similar age groups.", "contents": "[Quantitative and virus specific serum IgM detection in newborns (author's transl)]. Serum IgM concentration was determined in umbilical cord blood samples from 1000 newborns. 34 cases presenting elevated IgM values (greater than or equal to 30 mg%) were tested for virus specific IgM antibodies. We could demonstrate such virus specific IgM antibodies against Cytomegalovirus (4), against Rubella, Influenza A and Influenza B (2 each) and against Coxsackie virus (1). The quantitation of IgM in blood samples of child bearing women showed no elevated values compared to those of non-pregnant women of similar age groups."} {"id": "PMID:173653", "title": "Passive immunization in experimental Herpesvirus hominis infection of newborn mice.", "content": "Infection of newborn mice with Herpesvirus hominis type 2(HVH-2) was used as an experimental model of disseminated HVH infection in newborn humans. Mice were challenged with 103 plaque-forming units of HVH-2 intranasally and were given 0.2 ml of rabbit serum intraperitoneally. Passive immunizations with rabbit anti-HVH-2 serum resulted in a significant decrease in mortality and prolongation of survival time. This effect correlated with the neutralizing antibody titer of the serum against HVH-2 and was more pronounced when immune serum was administered 1 h after infection as compared with 24 h. These results suggest that administration of high-titer anti-HVH-2 immunoglobulins shortly after delivery could afford significant protection to the newborn of a mother with genital HVH-2 infection.", "contents": "Passive immunization in experimental Herpesvirus hominis infection of newborn mice. Infection of newborn mice with Herpesvirus hominis type 2(HVH-2) was used as an experimental model of disseminated HVH infection in newborn humans. Mice were challenged with 103 plaque-forming units of HVH-2 intranasally and were given 0.2 ml of rabbit serum intraperitoneally. Passive immunizations with rabbit anti-HVH-2 serum resulted in a significant decrease in mortality and prolongation of survival time. This effect correlated with the neutralizing antibody titer of the serum against HVH-2 and was more pronounced when immune serum was administered 1 h after infection as compared with 24 h. These results suggest that administration of high-titer anti-HVH-2 immunoglobulins shortly after delivery could afford significant protection to the newborn of a mother with genital HVH-2 infection."} {"id": "PMID:173654", "title": "Effect of anti-herpesvirus drugs on human and bovine lymphoid function in vitro.", "content": "Lymphocyte proliferative responses to phytohemagglutinin, pokeweed mitogen, and herpesvirus (herpes simplex virus and infectious bovine rhinotracheitis virus) antigens were evaluated in the presence of various concentrations of the anti-herpesvirus drugs, methylmethoxydeoxyuridine (OCH3CH2UdR), cytosine arabinoside was inhibitory at 25 mug/ml and cytosine arabinoside was inhibitory OCH3CH2UdR per ml, lymphocyte proliferative responses were unaffected and were not abolished even by concentrations of 2,500 mug/ml. In contrast, adenine arabinocide was inhibitory at 25 mug/ml and cytosine was inhibitory at 5 mug/ml. Both direct and antibody-dependent lymphocyte cytotoxicity of herpesvirus-infected target cells were highly resistant to OCH3CH2UdR; concentrations of 1,000 mug/ml were only marginally inhibitory. The anti-herpesvirus activity of all three drugs is similar (0.5 to 8 mug/ml) (L.A. Babiuk, B. Meldrum, V.S. Gupta, and B. T. Rouse, submitted for publication). The drug OCH3CH2UdR should be given a careful, well-controlled evaluation of its effectiveness in the treatment of herpes simplex infections in animals, perhaps including humans, since our results using in vitro models show that cellular responses important for recovery from herpesvirus infections are unaffected by doses far in excess of those found be be antiviral.", "contents": "Effect of anti-herpesvirus drugs on human and bovine lymphoid function in vitro. Lymphocyte proliferative responses to phytohemagglutinin, pokeweed mitogen, and herpesvirus (herpes simplex virus and infectious bovine rhinotracheitis virus) antigens were evaluated in the presence of various concentrations of the anti-herpesvirus drugs, methylmethoxydeoxyuridine (OCH3CH2UdR), cytosine arabinoside was inhibitory at 25 mug/ml and cytosine arabinoside was inhibitory OCH3CH2UdR per ml, lymphocyte proliferative responses were unaffected and were not abolished even by concentrations of 2,500 mug/ml. In contrast, adenine arabinocide was inhibitory at 25 mug/ml and cytosine was inhibitory at 5 mug/ml. Both direct and antibody-dependent lymphocyte cytotoxicity of herpesvirus-infected target cells were highly resistant to OCH3CH2UdR; concentrations of 1,000 mug/ml were only marginally inhibitory. The anti-herpesvirus activity of all three drugs is similar (0.5 to 8 mug/ml) (L.A. Babiuk, B. Meldrum, V.S. Gupta, and B. T. Rouse, submitted for publication). The drug OCH3CH2UdR should be given a careful, well-controlled evaluation of its effectiveness in the treatment of herpes simplex infections in animals, perhaps including humans, since our results using in vitro models show that cellular responses important for recovery from herpesvirus infections are unaffected by doses far in excess of those found be be antiviral."} {"id": "PMID:173655", "title": "Increased susceptibility to bacterial infection as a sequela of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.", "content": "The effects of subclinical levels of 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD) on the response of mice to infection with either Salmonella bern or Herpesvirus suis, also known as pseudorabies virus, are reported. TCDD is a contaminant of certain commercially useful chemicals, such as chlorinated phenols or herbicides. It has been shown to cause thymic atrophy and to suppress cell-mediated immunity in laboratory animals. Sublethal levels of TCDD were used: 0.5, 1,5, 10, or 20 mug/kg, given through a gastric tube once weekly for 4 weeks. A significant decrease in weight gain compared with control mice occurred at the 20-mug dosage. Dose schedules of 1 mug or more, followed by salmonella infection, resulted in significant increases in mortality and decreases in the time from infection to dealth. However, TCDD had no significant effect on mortality in the pseudorabies-infected mice. The most important finding in this study is that extremely low levels of TCDD, which do not produce clinical or pathological change, still have the capacity to affect host defense.", "contents": "Increased susceptibility to bacterial infection as a sequela of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. The effects of subclinical levels of 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD) on the response of mice to infection with either Salmonella bern or Herpesvirus suis, also known as pseudorabies virus, are reported. TCDD is a contaminant of certain commercially useful chemicals, such as chlorinated phenols or herbicides. It has been shown to cause thymic atrophy and to suppress cell-mediated immunity in laboratory animals. Sublethal levels of TCDD were used: 0.5, 1,5, 10, or 20 mug/kg, given through a gastric tube once weekly for 4 weeks. A significant decrease in weight gain compared with control mice occurred at the 20-mug dosage. Dose schedules of 1 mug or more, followed by salmonella infection, resulted in significant increases in mortality and decreases in the time from infection to dealth. However, TCDD had no significant effect on mortality in the pseudorabies-infected mice. The most important finding in this study is that extremely low levels of TCDD, which do not produce clinical or pathological change, still have the capacity to affect host defense."} {"id": "PMID:173652", "title": "Influence of fatty acids on pressor responses to catecholamines.", "content": "Lauric, Myristic and Palmitic acids had no appreciable effect whereas Stearic, Oleic and Linoleic acids caused some reduction in dog blood pressure. Pressor responses to epinephrine and nor-epinephrine were potentiated whereas the depressor response to isoproterenol was reduced during the infusion of fatty acids in dogs. ACTH alone, which causes mobilization of free fatty acids had no appreciable effect on blood pressure responses to catecholamines, however, its administration followed by salicylate produced marked potentiation of the pressor responses to epinephrine and nor-epinephrine; the depressor response to isoproterenol was reduced.", "contents": "Influence of fatty acids on pressor responses to catecholamines. Lauric, Myristic and Palmitic acids had no appreciable effect whereas Stearic, Oleic and Linoleic acids caused some reduction in dog blood pressure. Pressor responses to epinephrine and nor-epinephrine were potentiated whereas the depressor response to isoproterenol was reduced during the infusion of fatty acids in dogs. ACTH alone, which causes mobilization of free fatty acids had no appreciable effect on blood pressure responses to catecholamines, however, its administration followed by salicylate produced marked potentiation of the pressor responses to epinephrine and nor-epinephrine; the depressor response to isoproterenol was reduced."} {"id": "PMID:173656", "title": "Determination of subgroup-specific feline oncornavirus-neutralizing antibody.", "content": "A microneutralization assay was developed for antibody-to-subgroup-specific feline oncornaviruses. This study combines the economic advantage of a microtiter system and the quantitative focus reduction method which permits contruction of multiplicity curves for determination of virus-neutralizing titers. A twofold increase in Synder-Theilen feline sarcoma virus (ST-FeSV) on feline embryo cells decreased by approximately twofold the titer of reference goat serum prepared against Kawakami-Theilen feline leukemia virus. Similar dose effects with FeLV serotype virus preparations were not observed. An assay system utilizing FeLV serotypes on sarcoma-positive leukemia-negative cells demonstrated slightly greater sensitivity than one employing ST-FeSV on FE cells. Differential antibody responses to the three subgroup-specific feline oncornaviruses (A, B ,and C) were observed in reference goat sera. This test demonstrated good reproducibility as well as sensitivity and constitutes a significant improvement over end point dilution assay systems.", "contents": "Determination of subgroup-specific feline oncornavirus-neutralizing antibody. A microneutralization assay was developed for antibody-to-subgroup-specific feline oncornaviruses. This study combines the economic advantage of a microtiter system and the quantitative focus reduction method which permits contruction of multiplicity curves for determination of virus-neutralizing titers. A twofold increase in Synder-Theilen feline sarcoma virus (ST-FeSV) on feline embryo cells decreased by approximately twofold the titer of reference goat serum prepared against Kawakami-Theilen feline leukemia virus. Similar dose effects with FeLV serotype virus preparations were not observed. An assay system utilizing FeLV serotypes on sarcoma-positive leukemia-negative cells demonstrated slightly greater sensitivity than one employing ST-FeSV on FE cells. Differential antibody responses to the three subgroup-specific feline oncornaviruses (A, B ,and C) were observed in reference goat sera. This test demonstrated good reproducibility as well as sensitivity and constitutes a significant improvement over end point dilution assay systems."} {"id": "PMID:173657", "title": "Induction of herpes simplex virus immunity in newborn mice.", "content": "It was demonstrated that newborn mice, surviving an infection with attenuated herpes simplex virus, become resistant to challenge with a pathogenic strain of herpes simplex virus. This resistance did not seem to be mediated by antibody.", "contents": "Induction of herpes simplex virus immunity in newborn mice. It was demonstrated that newborn mice, surviving an infection with attenuated herpes simplex virus, become resistant to challenge with a pathogenic strain of herpes simplex virus. This resistance did not seem to be mediated by antibody."} {"id": "PMID:173658", "title": "An improved specific IgM antibody assay for Epstein-Barr virus.", "content": "A new method for detecting specific IgM antibodies to the Epstein-Barr virus using indirect fluorescence is presented. The procedure is simple and reproducible, and of great value for the diagnosis of an acute infection. The number of positive cells is higher than in the Epstein-Barr IgG test. It would seem that it is possible to detect a positive IgM-specific antigen with this new test.", "contents": "An improved specific IgM antibody assay for Epstein-Barr virus. A new method for detecting specific IgM antibodies to the Epstein-Barr virus using indirect fluorescence is presented. The procedure is simple and reproducible, and of great value for the diagnosis of an acute infection. The number of positive cells is higher than in the Epstein-Barr IgG test. It would seem that it is possible to detect a positive IgM-specific antigen with this new test."} {"id": "PMID:173661", "title": "Radical formation in salts of pyrimidines. II. Cytosine. HCl crystals.", "content": "Radicals produced by X-irradiation at 77 K and at 300 K of cytosine. HCl crystals have been analysed by electron spin resonance spectroscopy. Four radicals have been identified: the anion radical of the cytosine molecule, the radical resulting from H-addition at position C6, the radical resulting from H-addition at position O2, and finally a radical resulting from addition of a Cl- to nitrogen N3. H\u00fcckel molecular orbital calculations are presented, which support the hypothesis according to which in unsaturated pyrimidines the site of hydrogenation or protonation depends on the state of the molecule.", "contents": "Radical formation in salts of pyrimidines. II. Cytosine. HCl crystals. Radicals produced by X-irradiation at 77 K and at 300 K of cytosine. HCl crystals have been analysed by electron spin resonance spectroscopy. Four radicals have been identified: the anion radical of the cytosine molecule, the radical resulting from H-addition at position C6, the radical resulting from H-addition at position O2, and finally a radical resulting from addition of a Cl- to nitrogen N3. H\u00fcckel molecular orbital calculations are presented, which support the hypothesis according to which in unsaturated pyrimidines the site of hydrogenation or protonation depends on the state of the molecule."} {"id": "PMID:173662", "title": "Reassociation kinetics of DNA from x-irradiated ascites hepatoma cells of the rat.", "content": "The kinetics of the reassociation fo DNA from ascites hepatoma cells has been studied. The curve exhibited three zones corresponding to 'fast', 'intermediate' and 'slow' speeds of DNA reassociation. The difference was observed in the DNA reassociation curves of the control and irradiated (1500 rad) cells which was particularly expressed in the 'slow' zone (10(2) less than C0t less than 10(4). The same dose, however, does not qualitatively effect the secondary DNA structure, which was estimated by the method of thermal elution from the hydroxyapatite column.", "contents": "Reassociation kinetics of DNA from x-irradiated ascites hepatoma cells of the rat. The kinetics of the reassociation fo DNA from ascites hepatoma cells has been studied. The curve exhibited three zones corresponding to 'fast', 'intermediate' and 'slow' speeds of DNA reassociation. The difference was observed in the DNA reassociation curves of the control and irradiated (1500 rad) cells which was particularly expressed in the 'slow' zone (10(2) less than C0t less than 10(4). The same dose, however, does not qualitatively effect the secondary DNA structure, which was estimated by the method of thermal elution from the hydroxyapatite column."} {"id": "PMID:173663", "title": "E.s.r. studies of halogenated pyrimidines in gamma-irradiated alkaline glasses.", "content": "The reactions of mobile electrons (em-) and oxygen radical anions (O--) with halogenated bases and nucleosides have been studies in gamma-irradiated alkaline glasses by e.s.r. and specific halogen-ion electrode techniques. It is shown that electrons react with halogenated uracil bases (XUr where X = Cl, Br. I but not F) by dissociative electron attachment to form uracil-5-yl radicals (U-) and halogen anions. The relative rates of reaction of em- with XUr decrease in the sequence BrUr greater than ClUr greater than FUr greater than IUr. Thermal annealing studies carried out on U- in H2O and D2O matrices support the hypothesis that U- in H2O hydrates across the 5-6 double bond in the temperature region 135 degrees-155 degrees K, and deuterates to a much smaller extent in D2O at temperatures above 155 degrees K. Studies on bromouridine and bromodeoxyurinde suggest that em- reacts with the base moieties to form U- type radicals which abstract H- from the sugar moieties of adjacent nucleosides.", "contents": "E.s.r. studies of halogenated pyrimidines in gamma-irradiated alkaline glasses. The reactions of mobile electrons (em-) and oxygen radical anions (O--) with halogenated bases and nucleosides have been studies in gamma-irradiated alkaline glasses by e.s.r. and specific halogen-ion electrode techniques. It is shown that electrons react with halogenated uracil bases (XUr where X = Cl, Br. I but not F) by dissociative electron attachment to form uracil-5-yl radicals (U-) and halogen anions. The relative rates of reaction of em- with XUr decrease in the sequence BrUr greater than ClUr greater than FUr greater than IUr. Thermal annealing studies carried out on U- in H2O and D2O matrices support the hypothesis that U- in H2O hydrates across the 5-6 double bond in the temperature region 135 degrees-155 degrees K, and deuterates to a much smaller extent in D2O at temperatures above 155 degrees K. Studies on bromouridine and bromodeoxyurinde suggest that em- reacts with the base moieties to form U- type radicals which abstract H- from the sugar moieties of adjacent nucleosides."} {"id": "PMID:173667", "title": "Thoraco-abdominal approach in tumour nephrectomy.", "content": "In order to prevent intraoperative metastasis, venous invasion and infilitration of the regional lymph nodes by renal carcinoma, the thoraco-abdominal surgical approach is recommended. The vascular pedicle can in this way be explored and ligated before manipulation of the tumour. After total nephrectomy en bloc with the fatty capsule and adrenal gland, paracaval, paraaortal and intravasal lymphadenectomy is performed. Tumorous protrusions into the vena cava can mostly be removed at the same time. Inoperability rate could be reduced to 2.1 per cent as opposed to an earlier 11.3 per cent with the lumbar approach. TNM classification followed the recommendations of the UICC and was supplemented with a four-stage system. No improvement over the lumbar approach in respect of survival has been achieved in the first three postoperative years. However, local recurrence is expected to diminish as a result of improved radicality.", "contents": "Thoraco-abdominal approach in tumour nephrectomy. In order to prevent intraoperative metastasis, venous invasion and infilitration of the regional lymph nodes by renal carcinoma, the thoraco-abdominal surgical approach is recommended. The vascular pedicle can in this way be explored and ligated before manipulation of the tumour. After total nephrectomy en bloc with the fatty capsule and adrenal gland, paracaval, paraaortal and intravasal lymphadenectomy is performed. Tumorous protrusions into the vena cava can mostly be removed at the same time. Inoperability rate could be reduced to 2.1 per cent as opposed to an earlier 11.3 per cent with the lumbar approach. TNM classification followed the recommendations of the UICC and was supplemented with a four-stage system. No improvement over the lumbar approach in respect of survival has been achieved in the first three postoperative years. However, local recurrence is expected to diminish as a result of improved radicality."} {"id": "PMID:173668", "title": "Experimental studies with Staphylococcus aureus in M-K media.", "content": "This study reviewed the potential for survival of a pathogenic bacteria when inoculated into McCarey-Kaufman modified tissue culture media 199. A clinically isolated specimen of Staphylococcus aureus was selected and rabbit eyes inoculated with 0.1 ml. of the organism in a suspension of 1 to 3 x 10(-5). Upon enucleation 12 hours later no clinical signs of infection were noted. Limbal-conjunctival cultures were obtained on all eyes before and after application of the antibiotic. Corneas were stored in M-K media with standard penicillin-streptomycin added and cultured up to 48 hours. Our studies showed some recovery of the infecting organism from the media with topical antibiotic application but none following complete immersion of eyes in antibiotic. Direct cultures from corneal buttons taken 48 to 72 hours after antibiotic application by either method showed 1 to 3 colonies per plate in 25 per cent of eyes. In this study improperly applied antibiotic allowed some survival of S. aureus in the media.", "contents": "Experimental studies with Staphylococcus aureus in M-K media. This study reviewed the potential for survival of a pathogenic bacteria when inoculated into McCarey-Kaufman modified tissue culture media 199. A clinically isolated specimen of Staphylococcus aureus was selected and rabbit eyes inoculated with 0.1 ml. of the organism in a suspension of 1 to 3 x 10(-5). Upon enucleation 12 hours later no clinical signs of infection were noted. Limbal-conjunctival cultures were obtained on all eyes before and after application of the antibiotic. Corneas were stored in M-K media with standard penicillin-streptomycin added and cultured up to 48 hours. Our studies showed some recovery of the infecting organism from the media with topical antibiotic application but none following complete immersion of eyes in antibiotic. Direct cultures from corneal buttons taken 48 to 72 hours after antibiotic application by either method showed 1 to 3 colonies per plate in 25 per cent of eyes. In this study improperly applied antibiotic allowed some survival of S. aureus in the media."} {"id": "PMID:173669", "title": "Cytopathic effects in primary epithelial cultures derived from the human prostate.", "content": "Normal, benign, and malignant human prostatic tissue was cultivated in vitro. Cytopathic effects in derived epithelial cells were examined. Light microscopy revealed polykaryocyte formation, vacuolation, cytoplasmic bridges and processes, nuclear inclusions, increased acid phosphatase activity at the cell membrane of polykaryocytes as compared to mononuclear cells, and cell rounding and clumping. Electron microscopy of the polykaryocytes showed nuclear membrane proliferation and protrusion, scarlike nuclear inclusions containing microfibrils, and virus-like particles similiar to viral nucleoids and nucleocapsids. The latter were also observed in the cytoplasm. The above alterations are similar to those induced by known herpesviruses. The significance of these changes, the possibility of the presence of a latent herpesvirus in the prostate, and its role in neoplastic disease are postulated.", "contents": "Cytopathic effects in primary epithelial cultures derived from the human prostate. Normal, benign, and malignant human prostatic tissue was cultivated in vitro. Cytopathic effects in derived epithelial cells were examined. Light microscopy revealed polykaryocyte formation, vacuolation, cytoplasmic bridges and processes, nuclear inclusions, increased acid phosphatase activity at the cell membrane of polykaryocytes as compared to mononuclear cells, and cell rounding and clumping. Electron microscopy of the polykaryocytes showed nuclear membrane proliferation and protrusion, scarlike nuclear inclusions containing microfibrils, and virus-like particles similiar to viral nucleoids and nucleocapsids. The latter were also observed in the cytoplasm. The above alterations are similar to those induced by known herpesviruses. The significance of these changes, the possibility of the presence of a latent herpesvirus in the prostate, and its role in neoplastic disease are postulated."} {"id": "PMID:173670", "title": "A human adrenocortical adenoma in tissue culture. Morphology and hormone secretion.", "content": "A human adrenocortical adenoma was cultivated in vitro and the morphological characteristics, steroidogenic activity and response to ACTH of the cultured cells were studied over a period of about two months. At first, the morphology of the cultures was similar to that of the original tissue. This structure changed in the course of time and the cells underwent fibroblastoid transformation. Stimulation with ACTH evoked two types of morphological response: a) a short-term response, whereby an extensive but rapidly reversible vacuolization was followed by cell enlargement and granulation, and b) a long-term effect in which the differentiated cell morphology was maintained. The cultures showed a low steroidogenic activity throughout the experiment. ACTH stimulation increased the total 17-hydroxysteroid production up to 10-fold. After ACTH withdrawal the corticosteroid levels declined slowly and about 50% of the maximal activity persisted on the fifth day after ACTH withdrawal.", "contents": "A human adrenocortical adenoma in tissue culture. Morphology and hormone secretion. A human adrenocortical adenoma was cultivated in vitro and the morphological characteristics, steroidogenic activity and response to ACTH of the cultured cells were studied over a period of about two months. At first, the morphology of the cultures was similar to that of the original tissue. This structure changed in the course of time and the cells underwent fibroblastoid transformation. Stimulation with ACTH evoked two types of morphological response: a) a short-term response, whereby an extensive but rapidly reversible vacuolization was followed by cell enlargement and granulation, and b) a long-term effect in which the differentiated cell morphology was maintained. The cultures showed a low steroidogenic activity throughout the experiment. ACTH stimulation increased the total 17-hydroxysteroid production up to 10-fold. After ACTH withdrawal the corticosteroid levels declined slowly and about 50% of the maximal activity persisted on the fifth day after ACTH withdrawal."} {"id": "PMID:173698", "title": "Sodium chloride restriction and extracellular fluid volume contraction in hyperphosphatiuric vitamin D resistant rickets in the Lowe syndrome.", "content": "A patient with a Lowe syndrome was observed from birth. Progressive hyperchloraemic renal tubular acidosis, hypophosphataemia, hyperphosphaturia and generalized hyperaminoaciduria had developed in infancy. Supplementary vitamin D, alkali and a high intake of dietary phosphate were unsuccessful in controlling the severe phosphate diabetes and rickets. Contraction of the extracellular fluid volume by dietary sodium restriction resulted in correction of the acidosis, hypophosphataemia, hyperaminoaciduria, and hyperphosphaturia, and healing of the rickets.", "contents": "Sodium chloride restriction and extracellular fluid volume contraction in hyperphosphatiuric vitamin D resistant rickets in the Lowe syndrome. A patient with a Lowe syndrome was observed from birth. Progressive hyperchloraemic renal tubular acidosis, hypophosphataemia, hyperphosphaturia and generalized hyperaminoaciduria had developed in infancy. Supplementary vitamin D, alkali and a high intake of dietary phosphate were unsuccessful in controlling the severe phosphate diabetes and rickets. Contraction of the extracellular fluid volume by dietary sodium restriction resulted in correction of the acidosis, hypophosphataemia, hyperaminoaciduria, and hyperphosphaturia, and healing of the rickets."} {"id": "PMID:173699", "title": "Genital herpes simplex virus type 1 infection--variability in modes of spread.", "content": "Ever since the first report in 1967 of the association of herpes simplex virus type 2 (HSV-2) with urogenital infections, we have noted the occasional isolation of HSV-1 from such sites. Our most recent results of the typing of HSV isolates from 527 individuals with urogenital infections show that 10.9% of such infections in females and 3.4% in males are caused by HSV-1. We describe here the acquisition of a primary oral HSV-1 infection in a male after orogenital contact with his wife who had a primary genital HSV-1 infection, probably as a result of sexual contact with another male partner. The various modes of acquisition and spread of genital HSV-1, including nonvenereal routes, are reviewed. It is suggested that the influence of the microenvironment of the female genital tract on the selection of variants of microorganism--viruses, bacteria, etc--requires concerted study.", "contents": "Genital herpes simplex virus type 1 infection--variability in modes of spread. Ever since the first report in 1967 of the association of herpes simplex virus type 2 (HSV-2) with urogenital infections, we have noted the occasional isolation of HSV-1 from such sites. Our most recent results of the typing of HSV isolates from 527 individuals with urogenital infections show that 10.9% of such infections in females and 3.4% in males are caused by HSV-1. We describe here the acquisition of a primary oral HSV-1 infection in a male after orogenital contact with his wife who had a primary genital HSV-1 infection, probably as a result of sexual contact with another male partner. The various modes of acquisition and spread of genital HSV-1, including nonvenereal routes, are reviewed. It is suggested that the influence of the microenvironment of the female genital tract on the selection of variants of microorganism--viruses, bacteria, etc--requires concerted study."} {"id": "PMID:173700", "title": "Effect of desdanine on nucleoside diphosphate kinase and pyruvate kinase of Escherichia coli.", "content": "Kinetic analysis demonstrated that the irreversible inhibition of nucleoside diphosphate kinase of Escherichia coli by desdanine proceeds via a reversible Enzyme-Inhibitor complex. It is known that pyruvate kinase of E. coli becomes inactive upon prolonged dialysis in the absence of a reducing reagent, such as dithiothreitol and that the inactive enzyme is reactivated if dithiothretiol is added. Desdanine inhibits this reactivation process. The effect is discussed in relation to inhibition in relation to the inhibition of growth of E. coli by desdanine under anaerobic conditions. Pyruvate kinase of E. coli changes not only in intracellular quantity but in its kinetic characteristics depending on growth conditions, aerobic or anaerobic. The enzyme shows a broad specificity for nucleside diphosphates, especially in the presence of AMP, and thus resembles closely nucleoside diphosphate kinase. The in vivo role of pyruvate kinase in supplying nucleoside triphosphates under anaerobic conditions is discussed.", "contents": "Effect of desdanine on nucleoside diphosphate kinase and pyruvate kinase of Escherichia coli. Kinetic analysis demonstrated that the irreversible inhibition of nucleoside diphosphate kinase of Escherichia coli by desdanine proceeds via a reversible Enzyme-Inhibitor complex. It is known that pyruvate kinase of E. coli becomes inactive upon prolonged dialysis in the absence of a reducing reagent, such as dithiothreitol and that the inactive enzyme is reactivated if dithiothretiol is added. Desdanine inhibits this reactivation process. The effect is discussed in relation to inhibition in relation to the inhibition of growth of E. coli by desdanine under anaerobic conditions. Pyruvate kinase of E. coli changes not only in intracellular quantity but in its kinetic characteristics depending on growth conditions, aerobic or anaerobic. The enzyme shows a broad specificity for nucleside diphosphates, especially in the presence of AMP, and thus resembles closely nucleoside diphosphate kinase. The in vivo role of pyruvate kinase in supplying nucleoside triphosphates under anaerobic conditions is discussed."} {"id": "PMID:173703", "title": "An application of neuroendocrinological studies in autistic children and Heller's syndrome.", "content": "The response of plasma 11-hydroxycorticosteroids (11-OHCS) to intravenous pyrogen as well as the circadian rhythm of plasma 11-OHCS levels were investigated in seven autistic children and in two children with Heller's syndrome. In autistic children, the stress response, which is acquired in an earlier stage of development, was adequately sustained. However, the circadian rhythm, which seems to appear at a later stage with the maturity of the CNS, frequently revealed abnormal patterns. Similar findings were obtained in the Heller's syndrome cases, indicating organic changes in the brain. On the basis of these results, it is postulated that in early infantile autism there exist some functional changes in the CNS that show a close correlation to the regulatory mechanism of ACTH secretion.", "contents": "An application of neuroendocrinological studies in autistic children and Heller's syndrome. The response of plasma 11-hydroxycorticosteroids (11-OHCS) to intravenous pyrogen as well as the circadian rhythm of plasma 11-OHCS levels were investigated in seven autistic children and in two children with Heller's syndrome. In autistic children, the stress response, which is acquired in an earlier stage of development, was adequately sustained. However, the circadian rhythm, which seems to appear at a later stage with the maturity of the CNS, frequently revealed abnormal patterns. Similar findings were obtained in the Heller's syndrome cases, indicating organic changes in the brain. On the basis of these results, it is postulated that in early infantile autism there exist some functional changes in the CNS that show a close correlation to the regulatory mechanism of ACTH secretion."} {"id": "PMID:173704", "title": "Specific inhibition of phospholipid synthesis in plsA mutants of Escherichia coli.", "content": "plsA mutants of Escherichia coli are temperature-sensitive strains which possess two enzymes of abnormal thermolability, sn-glycerol 3-phosphate acyltransferase and adenylate kinase. Phospholipid synthesis is inhibited after shift of plsA mutants to temperatures at the lower end of the nonpermissive temperature range. This inhibition is not due to inactivation of the adenylate kinase activity since nucleic acid (and hence adenosine 5'-triphosphate) synthesis is inhibited only slightly. These results show that in vivo inactivation of the sn-glycerol 3-phosphate acyltransferase can be observed under conditions which allow normal adenylate kinase function.", "contents": "Specific inhibition of phospholipid synthesis in plsA mutants of Escherichia coli. plsA mutants of Escherichia coli are temperature-sensitive strains which possess two enzymes of abnormal thermolability, sn-glycerol 3-phosphate acyltransferase and adenylate kinase. Phospholipid synthesis is inhibited after shift of plsA mutants to temperatures at the lower end of the nonpermissive temperature range. This inhibition is not due to inactivation of the adenylate kinase activity since nucleic acid (and hence adenosine 5'-triphosphate) synthesis is inhibited only slightly. These results show that in vivo inactivation of the sn-glycerol 3-phosphate acyltransferase can be observed under conditions which allow normal adenylate kinase function."} {"id": "PMID:173705", "title": "Spin-labeling studies on the lipids of psychrophilic, psychrotrophic, and mesophilic clostridia.", "content": "Spin-labeling studies were conducted to elucidate the viscosity and phase transition temperatures of lipids isolated from psychrophilic, psychrotrophic, and mesophilic clostridia. Electron spin resonance spectroscopy indicated that the lipids, for all the growth temperatures tested, were in a fluid state and from 13 to 24 C higher than the corresponding lipid transition temperatures. When the organisms were grown at different temperatures, a psychrotropic and two mesophilic clostridia were shown to be able to adjust their lipid-phase transition temperature to the growth temperature. A psychrophilic Clostridium strain, when grown at different temperatures, synthesized lipids that had the same phase transition temperature. It is suggested that this lack of growth temperature-inducible regulation of lipid-phase transition temperature may be a molecular determinant for the psychrophily of this organism. It is proposed that the growth temperature range of an organism is dependent upon the ability of the organism to regulate its lipid fluidity within a specific range.", "contents": "Spin-labeling studies on the lipids of psychrophilic, psychrotrophic, and mesophilic clostridia. Spin-labeling studies were conducted to elucidate the viscosity and phase transition temperatures of lipids isolated from psychrophilic, psychrotrophic, and mesophilic clostridia. Electron spin resonance spectroscopy indicated that the lipids, for all the growth temperatures tested, were in a fluid state and from 13 to 24 C higher than the corresponding lipid transition temperatures. When the organisms were grown at different temperatures, a psychrotropic and two mesophilic clostridia were shown to be able to adjust their lipid-phase transition temperature to the growth temperature. A psychrophilic Clostridium strain, when grown at different temperatures, synthesized lipids that had the same phase transition temperature. It is suggested that this lack of growth temperature-inducible regulation of lipid-phase transition temperature may be a molecular determinant for the psychrophily of this organism. It is proposed that the growth temperature range of an organism is dependent upon the ability of the organism to regulate its lipid fluidity within a specific range."} {"id": "PMID:173706", "title": "Ultrastructural study of polymyxin-resistant isolates of Pseudomonas aeruginosa.", "content": "Upon exposure to 6,000 U of polymyxin B sulfate per ml, cells of the polymyxin-sensitive PAO 1 strain of Pseudomonas aeruginosa displayed in thin sections long projections arising from the outer membrane of the cell wall and extensive cytoplasmic degradation with accumulation of cytoplasmic membrane infoldings. Polymyxin-resistant isolates derived from the PAO 1 strain, however, grew well in the presence of 6,000 U of polymyxin per ml and exhibited none of these effects, having instead the appearance of a typically healthy cell. Freeze-etching of cells of the sensitive strain grown in basal medium without polymyxin revealed a concave cell wall layer studded with numerous particles. Freeze-etching of cells of the resistant isolates grown in basal medium containing 6,000 U of polymyxin per ml revealed a concave cell wall layer (i.e., the outer half of the outer membrane) in which most of these particles were absent. Thus, acquisition of resistance to polymyxin was correlated with an alteration in the architecture of the outer membrane. When the resistant isolates were grown in the basal medium lacking polymyxin and then freeze-etched, the particle distribution in the concave cell wall layer resembled that of the sensitive parent strain. The cells had regained sensitivity to polymyxin upon suspension in medium containing 6,000 U/ml as determined by their failure to grow and by internal damages seen in thin sections. These cells also had acquired increased sensitivity to ethylenediaminetetraacetate, whereas the polymyxin-resistant cells grown in the presence of polymyxin were resistant to lysis by ethylenediaminetetraacetate. The polymyxin-resistant isolates were not stable mutants but instead represented an adaptive response to the presence of polymyxin in the medium.", "contents": "Ultrastructural study of polymyxin-resistant isolates of Pseudomonas aeruginosa. Upon exposure to 6,000 U of polymyxin B sulfate per ml, cells of the polymyxin-sensitive PAO 1 strain of Pseudomonas aeruginosa displayed in thin sections long projections arising from the outer membrane of the cell wall and extensive cytoplasmic degradation with accumulation of cytoplasmic membrane infoldings. Polymyxin-resistant isolates derived from the PAO 1 strain, however, grew well in the presence of 6,000 U of polymyxin per ml and exhibited none of these effects, having instead the appearance of a typically healthy cell. Freeze-etching of cells of the sensitive strain grown in basal medium without polymyxin revealed a concave cell wall layer studded with numerous particles. Freeze-etching of cells of the resistant isolates grown in basal medium containing 6,000 U of polymyxin per ml revealed a concave cell wall layer (i.e., the outer half of the outer membrane) in which most of these particles were absent. Thus, acquisition of resistance to polymyxin was correlated with an alteration in the architecture of the outer membrane. When the resistant isolates were grown in the basal medium lacking polymyxin and then freeze-etched, the particle distribution in the concave cell wall layer resembled that of the sensitive parent strain. The cells had regained sensitivity to polymyxin upon suspension in medium containing 6,000 U/ml as determined by their failure to grow and by internal damages seen in thin sections. These cells also had acquired increased sensitivity to ethylenediaminetetraacetate, whereas the polymyxin-resistant cells grown in the presence of polymyxin were resistant to lysis by ethylenediaminetetraacetate. The polymyxin-resistant isolates were not stable mutants but instead represented an adaptive response to the presence of polymyxin in the medium."} {"id": "PMID:173707", "title": "Mutants of Aspergillus nidulans lacking nicotinamide adenine dinucleotide-specific glutamate dehydrogenase.", "content": "Ten mutants of Aspergillus nidulans lacking nicotinamide adenine dinucleotide-specific glutamate dehydrogenase (NAD-GDH) have been isolated, and their mutations (gdhB1 through gdhB10) have been shown to lie in the gdhB gene. In addition, a temperature-sensitive gdhB mutant (gdhB11) has been isolated. A revertant (designated R-5) of the mutant gdhB1 bears an additional lesion in the gdhB gene and has altered NAD-GDH activity with altered Km values for ammonia or ammonium ions and for alpha-ketoglutarate. These results suggest that gdhB specifies a structural component for NAD-GDH. The growth characteristics of gdhB mutants indicate the routes by which amino acids are utilized as nitrogen and carbon energy sources. The properties are described of the double mutants bearing the mutations gdhB1 and gdhA1 or tamA119, which have low NADP-GDH activity.", "contents": "Mutants of Aspergillus nidulans lacking nicotinamide adenine dinucleotide-specific glutamate dehydrogenase. Ten mutants of Aspergillus nidulans lacking nicotinamide adenine dinucleotide-specific glutamate dehydrogenase (NAD-GDH) have been isolated, and their mutations (gdhB1 through gdhB10) have been shown to lie in the gdhB gene. In addition, a temperature-sensitive gdhB mutant (gdhB11) has been isolated. A revertant (designated R-5) of the mutant gdhB1 bears an additional lesion in the gdhB gene and has altered NAD-GDH activity with altered Km values for ammonia or ammonium ions and for alpha-ketoglutarate. These results suggest that gdhB specifies a structural component for NAD-GDH. The growth characteristics of gdhB mutants indicate the routes by which amino acids are utilized as nitrogen and carbon energy sources. The properties are described of the double mutants bearing the mutations gdhB1 and gdhA1 or tamA119, which have low NADP-GDH activity."} {"id": "PMID:173708", "title": "Spore membrane(s) as the site of damage within heated Clostridium perfringens spores.", "content": "Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis.", "contents": "Spore membrane(s) as the site of damage within heated Clostridium perfringens spores. Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis."} {"id": "PMID:173709", "title": "Synthesis of deoxyribonucleic acid, ribonucleic acid, and protein during sporulation of Clostridium perfringens.", "content": "The kinetics of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein synthesis as well as protein breakdown during sporulation by Clostridium perfringens were determined. Maximum levels of DNA and net RNA synthesis occurred 3 and 2 h, respectively, after inoculation of sporulation medium. The rate of RNA synthesis decreased as sporulation progressed. Deoxyadenosine increased uptake of [14C]uracil and [14C]thymine but depressed the level of sporulation and the formation of heat-resistant spores when added at concentrations above 100 mug/ml. Unlike Bacillus species, net protein synthesis, which was sensitive to chloramphenicol inhibition, continued during sporulation. The rate of protein breakdown during vegetative growth was 1%/h. During sporulation this rate increased to 4.7%/h. When added to sporulation medium at 0 time chloramphenicol reduced protein breakdown to 1%/h. If added at 3 h the rate decreased to 2.1%/h. The role of proteases in this process is discussed.", "contents": "Synthesis of deoxyribonucleic acid, ribonucleic acid, and protein during sporulation of Clostridium perfringens. The kinetics of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein synthesis as well as protein breakdown during sporulation by Clostridium perfringens were determined. Maximum levels of DNA and net RNA synthesis occurred 3 and 2 h, respectively, after inoculation of sporulation medium. The rate of RNA synthesis decreased as sporulation progressed. Deoxyadenosine increased uptake of [14C]uracil and [14C]thymine but depressed the level of sporulation and the formation of heat-resistant spores when added at concentrations above 100 mug/ml. Unlike Bacillus species, net protein synthesis, which was sensitive to chloramphenicol inhibition, continued during sporulation. The rate of protein breakdown during vegetative growth was 1%/h. During sporulation this rate increased to 4.7%/h. When added to sporulation medium at 0 time chloramphenicol reduced protein breakdown to 1%/h. If added at 3 h the rate decreased to 2.1%/h. The role of proteases in this process is discussed."} {"id": "PMID:173710", "title": "Properties of adenyl cyclase and cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli.", "content": "Several spontaneous cya and crp mutants of Escherichia coli have been selected as clones simultaneously resistant to phage lambda and nalidixic acid and characterized. Both cya and crp mutants have been found to grow as cocci with increased doubling times. They have increased resistance to some mutagens (methylmethanesulfonate, ultraviolet light, gamma rays), antibiotics (nalidixic acid, ampicillin), phages (lambda, T6), sublethal heat and hypotonic shock, and decreased resistance to neutral detergents (sodium dodecyl sulfate, sodium deoxycholate), a protein synthesis inhibitor (streptomycin), and a respiratory inhibitor (sodium azide). The nature of changes in cell parameters indicate fundamental alterations in the envelope structure of the cya and crp mutant cells. The new cya and crp mutants have been found to be multiply carbohydrate negative and nonmotile in conformity with similar previously isolated mutants. Studies of revertants and phi80 cya+ and phi80 cya transductants indicated that the pleiotropic phenotype is related to a single mutational event at the cya or the crp locus in the mutants.", "contents": "Properties of adenyl cyclase and cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli. Several spontaneous cya and crp mutants of Escherichia coli have been selected as clones simultaneously resistant to phage lambda and nalidixic acid and characterized. Both cya and crp mutants have been found to grow as cocci with increased doubling times. They have increased resistance to some mutagens (methylmethanesulfonate, ultraviolet light, gamma rays), antibiotics (nalidixic acid, ampicillin), phages (lambda, T6), sublethal heat and hypotonic shock, and decreased resistance to neutral detergents (sodium dodecyl sulfate, sodium deoxycholate), a protein synthesis inhibitor (streptomycin), and a respiratory inhibitor (sodium azide). The nature of changes in cell parameters indicate fundamental alterations in the envelope structure of the cya and crp mutant cells. The new cya and crp mutants have been found to be multiply carbohydrate negative and nonmotile in conformity with similar previously isolated mutants. Studies of revertants and phi80 cya+ and phi80 cya transductants indicated that the pleiotropic phenotype is related to a single mutational event at the cya or the crp locus in the mutants."} {"id": "PMID:173711", "title": "Suppressor-induced structural changes in a missense L-ribulokinase of Escherichia coli.", "content": "A suppressor mutation specific for a missense codon in the L-ribulokinase structural gene of the L-arabinose operon of Escherichia coli B/r enhanced L-arabinose utilization by the strain containing the missense codon. Electrophoretic comparisons of the wild-type, missense, and suppressed missense L-ribulokinases indicated that the suppressor changed the structure of the missense kinase, thereby increasing its catalytic activity. Hyperinducibility imposed on an operator-distal gene by the missense codon was not affected by the suppressor mutation.", "contents": "Suppressor-induced structural changes in a missense L-ribulokinase of Escherichia coli. A suppressor mutation specific for a missense codon in the L-ribulokinase structural gene of the L-arabinose operon of Escherichia coli B/r enhanced L-arabinose utilization by the strain containing the missense codon. Electrophoretic comparisons of the wild-type, missense, and suppressed missense L-ribulokinases indicated that the suppressor changed the structure of the missense kinase, thereby increasing its catalytic activity. Hyperinducibility imposed on an operator-distal gene by the missense codon was not affected by the suppressor mutation."} {"id": "PMID:173712", "title": "Lethal effect of mitomycin C on Haemophilus influenzae.", "content": "The sensitivity of ultraviolet-sensitive strains to inactivation by mitomycin C (MC) is at the most only a factor of two greater than that of the wild type. The presence of inducible prophage has very little effect on the sensitivity. Genes which control excision of ultraviolet-induced pyrimidine dimers also control repair of MC-induced cross-links, as measured by resistance of denatured deoxyribonucleic acid (DNA) from treated cells to S1 nuclease digestion. However, endonucleolytic breaks in MC-damaged DNA, as judged by decreased single-strand molecular weight upon incubation of treated cells, are independent of these genes and probably are caused by monoadducts. After long periods of incubation there is a return to the molecular weight of untreated DNA. DNA degradation after MC treatment of various strains is not correlated with sensitivity to inactivation. Stationary-phase cells of all strains are more than twice as sensitive to MC as exponentially growing cells, and the sensitivity difference agrees with the measured difference in the number of cross-links after MC treatment of cells in the two growth stages. Evidence has been obtained that these phenomena result from differences in uptake of MC, which can be influenced by cyclic adenosine monophosphate. Small deviations in MC sensitivity from that of the wild type observed in mutants lacking the adenosine 5'-triphosphate-dependent nuclease are postulated to result from differences in MC uptake. These mutants, although no more ultraviolet sensitive than the wild type, are more sensitive to streptomycin, which also must be taken up by the cell to be effective.", "contents": "Lethal effect of mitomycin C on Haemophilus influenzae. The sensitivity of ultraviolet-sensitive strains to inactivation by mitomycin C (MC) is at the most only a factor of two greater than that of the wild type. The presence of inducible prophage has very little effect on the sensitivity. Genes which control excision of ultraviolet-induced pyrimidine dimers also control repair of MC-induced cross-links, as measured by resistance of denatured deoxyribonucleic acid (DNA) from treated cells to S1 nuclease digestion. However, endonucleolytic breaks in MC-damaged DNA, as judged by decreased single-strand molecular weight upon incubation of treated cells, are independent of these genes and probably are caused by monoadducts. After long periods of incubation there is a return to the molecular weight of untreated DNA. DNA degradation after MC treatment of various strains is not correlated with sensitivity to inactivation. Stationary-phase cells of all strains are more than twice as sensitive to MC as exponentially growing cells, and the sensitivity difference agrees with the measured difference in the number of cross-links after MC treatment of cells in the two growth stages. Evidence has been obtained that these phenomena result from differences in uptake of MC, which can be influenced by cyclic adenosine monophosphate. Small deviations in MC sensitivity from that of the wild type observed in mutants lacking the adenosine 5'-triphosphate-dependent nuclease are postulated to result from differences in MC uptake. These mutants, although no more ultraviolet sensitive than the wild type, are more sensitive to streptomycin, which also must be taken up by the cell to be effective."} {"id": "PMID:173713", "title": "Galactosaminogalactan from cell walls of Aspergillus niger.", "content": "A new heteropolysaccharide has been isolated by alkaline extraction of hyphal walls of Aspergillus niger NRRL 326 grown in surface culture. Its composition by weight, as determined by paper and gas chromatography and colorimetric analyses, is 70% galactose, 20% galactosamine, 6% glucose, and 1% acetyl. Two independent experiments have been used to ascertain copolymer structure: permeation chromatography in 6 M guanidinium hydrochloride, with controlled-pore glass columns of two fractionation ranges, and nitrous acid deaminative cleavage of galactosaminogalactan followed by reduction of fragments with [3H]borohydride and gel filtration chromatography. One of the tritiated fragments is tentatively identified as the disaccharide derivative galactopyranosyl 2,5-anhydrotalitol, on the basis of chromatographic properties and by kinetics of its acid hydrolysis. Smith degradation, methylation, deamination, and optical rotation studies indicate that the galactosaminogalactan consists of a linear array of hexopyranosyl units joined almost exclusively by alpha-(1 leads to 4) linkages. Hexosaminyl moieties are distributed randomly along the chains, which have an average degree of polymerization of about 100. The possible significance of this macromolecule in hyphal structure is considered.", "contents": "Galactosaminogalactan from cell walls of Aspergillus niger. A new heteropolysaccharide has been isolated by alkaline extraction of hyphal walls of Aspergillus niger NRRL 326 grown in surface culture. Its composition by weight, as determined by paper and gas chromatography and colorimetric analyses, is 70% galactose, 20% galactosamine, 6% glucose, and 1% acetyl. Two independent experiments have been used to ascertain copolymer structure: permeation chromatography in 6 M guanidinium hydrochloride, with controlled-pore glass columns of two fractionation ranges, and nitrous acid deaminative cleavage of galactosaminogalactan followed by reduction of fragments with [3H]borohydride and gel filtration chromatography. One of the tritiated fragments is tentatively identified as the disaccharide derivative galactopyranosyl 2,5-anhydrotalitol, on the basis of chromatographic properties and by kinetics of its acid hydrolysis. Smith degradation, methylation, deamination, and optical rotation studies indicate that the galactosaminogalactan consists of a linear array of hexopyranosyl units joined almost exclusively by alpha-(1 leads to 4) linkages. Hexosaminyl moieties are distributed randomly along the chains, which have an average degree of polymerization of about 100. The possible significance of this macromolecule in hyphal structure is considered."} {"id": "PMID:173714", "title": "Transformation of Escherichia coli by chromosomal deoxyribonucleic acid from Salmonella typhi.", "content": "The genetic transformation of Escherichia coli K-12 with chromosomal deoxyribonucleic acid purified from Salmonella typhi is described.", "contents": "Transformation of Escherichia coli by chromosomal deoxyribonucleic acid from Salmonella typhi. The genetic transformation of Escherichia coli K-12 with chromosomal deoxyribonucleic acid purified from Salmonella typhi is described."} {"id": "PMID:173715", "title": "Studies on cytochrome oxidase. Preliminary characterization of an enzyme containing only four subunits.", "content": "The preparation of a four-subunit enzyme from yeast, capable of catalyzing the oxidation of ferrocytochrome c, is described. It is derived from proteins containing seven or five subunits by means of recycling exclusion chromatography in the presence of 0.1% sodium dodecyl sulfate. Its catalytic properties are similar to those of the parent enzyme. Gel electrophoresis of this preparation in the presence of sodium dodecyl sulfate reveals three bands, migrating with RF values that correspond to molecular weights of 14.6, 12.3, and 10.6 X 10(3), with the largest exhibiting an apparent 2:1 stoichiometry relative to the other two. Visible spectra in the region of 390 to 630 nm do not show any detectable difference from that of the parent cytochrome oxidase, while its heme a and copper content are raised to values around 20 nmol or ng atoms/mg of protein, respectively, corresponding to minimal molecular weights of 50 X 10(3). The molecular weight determined by physical means equals 107 X 10(3). Thus the enzyme probably contains two copies of each subunit. After extensive dialysis to remove as much as possible of the sodium dodecyl sulfate used in its preparation, this enzyme remains in solution in phosphate buffer in the absence of any added detergent, while under similar conditions the seven-subunit complex precipitates completely. A similar preparation can also be obtained from beef heart. The significance of these findings is discussed with respect to the role of the large subunits in the function as well as the biogenesis of the mitochondrial cytochrome oxidase complex.", "contents": "Studies on cytochrome oxidase. Preliminary characterization of an enzyme containing only four subunits. The preparation of a four-subunit enzyme from yeast, capable of catalyzing the oxidation of ferrocytochrome c, is described. It is derived from proteins containing seven or five subunits by means of recycling exclusion chromatography in the presence of 0.1% sodium dodecyl sulfate. Its catalytic properties are similar to those of the parent enzyme. Gel electrophoresis of this preparation in the presence of sodium dodecyl sulfate reveals three bands, migrating with RF values that correspond to molecular weights of 14.6, 12.3, and 10.6 X 10(3), with the largest exhibiting an apparent 2:1 stoichiometry relative to the other two. Visible spectra in the region of 390 to 630 nm do not show any detectable difference from that of the parent cytochrome oxidase, while its heme a and copper content are raised to values around 20 nmol or ng atoms/mg of protein, respectively, corresponding to minimal molecular weights of 50 X 10(3). The molecular weight determined by physical means equals 107 X 10(3). Thus the enzyme probably contains two copies of each subunit. After extensive dialysis to remove as much as possible of the sodium dodecyl sulfate used in its preparation, this enzyme remains in solution in phosphate buffer in the absence of any added detergent, while under similar conditions the seven-subunit complex precipitates completely. A similar preparation can also be obtained from beef heart. The significance of these findings is discussed with respect to the role of the large subunits in the function as well as the biogenesis of the mitochondrial cytochrome oxidase complex."} {"id": "PMID:173716", "title": "Interaction of glucocorticoid receptor-steroid complexes with acceptor sites.", "content": "The binding of the \"activated\" receptor-glucocorticoid complexes of cultured rat hepatoma cells to nuclei, chromatin, and DNA has been studied under cell-free conditions. A critical factor in determining the shape of the binding curve is shown to be an inhibitory material which is present in crude cytosol and which can be removed without destroying the receptor-steroid complex. These and other results argue that the apparent saturation observed in earlier experiments may have been due to the inhibitors. Thus, the actual number of acceptor sites in hepatoma tissue culture cell nuclei is much larger than previously estimated and their affinity for the complex is lower. Nuclear binding experiments indicate that the inhibitory material interacts with the receptor-steroid complex. The inhibitors appear to be macromolecular; but their effects cannot be mimicked by albumin or hemoglobin. The acceptor capacity at low ionic strength for binding receptor-glucocorticoid complexes increases when proceeding from nuclei to DNA. An analysis of the kinetics of association and dissociation and of the relative binding behavior of nuclei and DNA argues that the affinity of complex for nuclei is much greater than for DNA. DNA-associated histones reduce the amount of complex that binds to DNA. These and perhaps other chromosomal proteins may be responsible for the ordering of acceptor capacity. Evidence is presented that the difference in affinities of nuclear and DNA acceptors could also be due to chromosomal proteins. In nuclei, these proteins may thus both reduce the amount of complex binding by rendering regions of DNA less accessible and increase the binding affinity of some, or all, of those DNA binding sites which remain exposed.", "contents": "Interaction of glucocorticoid receptor-steroid complexes with acceptor sites. The binding of the \"activated\" receptor-glucocorticoid complexes of cultured rat hepatoma cells to nuclei, chromatin, and DNA has been studied under cell-free conditions. A critical factor in determining the shape of the binding curve is shown to be an inhibitory material which is present in crude cytosol and which can be removed without destroying the receptor-steroid complex. These and other results argue that the apparent saturation observed in earlier experiments may have been due to the inhibitors. Thus, the actual number of acceptor sites in hepatoma tissue culture cell nuclei is much larger than previously estimated and their affinity for the complex is lower. Nuclear binding experiments indicate that the inhibitory material interacts with the receptor-steroid complex. The inhibitors appear to be macromolecular; but their effects cannot be mimicked by albumin or hemoglobin. The acceptor capacity at low ionic strength for binding receptor-glucocorticoid complexes increases when proceeding from nuclei to DNA. An analysis of the kinetics of association and dissociation and of the relative binding behavior of nuclei and DNA argues that the affinity of complex for nuclei is much greater than for DNA. DNA-associated histones reduce the amount of complex that binds to DNA. These and perhaps other chromosomal proteins may be responsible for the ordering of acceptor capacity. Evidence is presented that the difference in affinities of nuclear and DNA acceptors could also be due to chromosomal proteins. In nuclei, these proteins may thus both reduce the amount of complex binding by rendering regions of DNA less accessible and increase the binding affinity of some, or all, of those DNA binding sites which remain exposed."} {"id": "PMID:173717", "title": "Group translocation of the ribose moiety of inosine by vesicles of plasma membrane from T(3 cells transformed by Simian virus 40.", "content": "Plasma membrane vesicles are isolated from Simian virus 40-transformed Balb/c mouse 3T3 (SV-3T3) cells. These membrane vesicles contain no significant contamination by mitochondria, endoplasmic reticulum, or lysosomes as determined by marker enzyme analysis. The use of [U-14C] inosine as a transport substrate results in the accumulation of labeled ribose-1P as transport product by the plasma membrane vesicles. This suggests the action of purine nucleoside phosphorylase (the enzyme which mediates the phosphorolysis of inosine to ribose-1-P and hypoxanthine0 before, during, or after the transport step. Neither inosine nor significant amounts of hypoxanthine are found intravesicularly. The Km for inosine, the substrate in this reaction which leads to the accumulation of ribose-1-P by the plasma membrane vesicles, is 35 to 45 muM while the Vmax for ribose-1-P accumulation is 100 to 120 pmol/min/mg of plasma membrane protein...", "contents": "Group translocation of the ribose moiety of inosine by vesicles of plasma membrane from T(3 cells transformed by Simian virus 40. Plasma membrane vesicles are isolated from Simian virus 40-transformed Balb/c mouse 3T3 (SV-3T3) cells. These membrane vesicles contain no significant contamination by mitochondria, endoplasmic reticulum, or lysosomes as determined by marker enzyme analysis. The use of [U-14C] inosine as a transport substrate results in the accumulation of labeled ribose-1P as transport product by the plasma membrane vesicles. This suggests the action of purine nucleoside phosphorylase (the enzyme which mediates the phosphorolysis of inosine to ribose-1-P and hypoxanthine0 before, during, or after the transport step. Neither inosine nor significant amounts of hypoxanthine are found intravesicularly. The Km for inosine, the substrate in this reaction which leads to the accumulation of ribose-1-P by the plasma membrane vesicles, is 35 to 45 muM while the Vmax for ribose-1-P accumulation is 100 to 120 pmol/min/mg of plasma membrane protein..."} {"id": "PMID:173719", "title": "Effect of L-3,4-dehydroproline on collagen synthesis and prolyl hydroxylase activity in mammalian cell cultures.", "content": "The incorporation of DL-3,4-dehydro[14C]proline into collagen and total protein of 3T3 cells occurred at approximately one-fifth the rate observed for L-[14C]proline. Addition of L-3,4-dehydroproline to the culture medium inhibited markedly the incorporation of [14C]glycine and L-[3H]lysine into the collagen of 3T3 cells, but there was only slight inhibition of the incorporation of the radiolabeled amino acids into total cellular proteins, indicating that the action of L-3,4-dehydroproline is specific for collagen. When 1 mM L-3,4-dehydroproline was added to the culture medium the [14C]hydroxyproline content was reduced 40% in the cell layer and 70% in the medium. The D isomer of 3,4-dehydroproline did not inhibit [14C]hydroxyproline formation. These findings indicate that L-3,4-dehydroline reduced the hydroxylation of the susceptible prolyl residues in the collagen molecule and the secretion of collagen from the cell. The reduction in the hydroxyproline content is probably related in part to a reduction in the activity of prolyl hydroxylase; when various mammalian cell cultures were exposed to 0.2 mM L-3,4-dehydroproline, the specific activity of prolyl hydroxylase was reduced markedly, while that of lysyl hydroproline, the specific activity of prolyl hydroxylase was reduced markedly, while that of lysyl hydroxylase was not affected. Under these conditions, cell growth and lactic dehydrogenase required protein synthesis. Removal of L-3,4-dehydroproline from the growth medium resulted in a time-dependent increase in the specific activity of prolyl hydroxylase.", "contents": "Effect of L-3,4-dehydroproline on collagen synthesis and prolyl hydroxylase activity in mammalian cell cultures. The incorporation of DL-3,4-dehydro[14C]proline into collagen and total protein of 3T3 cells occurred at approximately one-fifth the rate observed for L-[14C]proline. Addition of L-3,4-dehydroproline to the culture medium inhibited markedly the incorporation of [14C]glycine and L-[3H]lysine into the collagen of 3T3 cells, but there was only slight inhibition of the incorporation of the radiolabeled amino acids into total cellular proteins, indicating that the action of L-3,4-dehydroproline is specific for collagen. When 1 mM L-3,4-dehydroproline was added to the culture medium the [14C]hydroxyproline content was reduced 40% in the cell layer and 70% in the medium. The D isomer of 3,4-dehydroproline did not inhibit [14C]hydroxyproline formation. These findings indicate that L-3,4-dehydroline reduced the hydroxylation of the susceptible prolyl residues in the collagen molecule and the secretion of collagen from the cell. The reduction in the hydroxyproline content is probably related in part to a reduction in the activity of prolyl hydroxylase; when various mammalian cell cultures were exposed to 0.2 mM L-3,4-dehydroproline, the specific activity of prolyl hydroxylase was reduced markedly, while that of lysyl hydroproline, the specific activity of prolyl hydroxylase was reduced markedly, while that of lysyl hydroxylase was not affected. Under these conditions, cell growth and lactic dehydrogenase required protein synthesis. Removal of L-3,4-dehydroproline from the growth medium resulted in a time-dependent increase in the specific activity of prolyl hydroxylase."} {"id": "PMID:173720", "title": "Effect of estrogen on gene expression in the chick oviduct. Correlation between nuclear-bound estrogen receptor and chromatin initiation site for transcription.", "content": "The [3H]estradiol exchange assay was used to characterize the nuclear estrogen receptor from the chick oviduct. After diethylstilibestrol (DES) treatment (14 days), the oviduct nuclei contained estrogen receptors that manifested high affinity (Kd = 2 X 10(-9)M) and low capacity binding (4000 to 5000 sites/cell) for estradiol. DES and estradiol competed significantly for [3H]estradiol binding, while testosterone and progesterone were ineffective. These binding sites were found in the oviduct and liver but not in the spleen, kidney, or muscle. Following salt extraction from nuclei, the receptor had a sedimentation coefficient of 4 S when analyzed by centrifugation in high and low salt sucrose density gradients. The [3H]estradiol exchange assay was used to examine the relationships between nuclear-bound receptor and RNA polymerase initiation sites on oviduct chromatin. Within 20 min after a single injection of 2.5 mg of DES to withdrawn chicks, a maximum number of estradiol receptor-binding sites was detected in oviduct nuclei. Within 30 min after DES injection, the total number of RNA initiation sites also increased, reaching 100% of control values. Daily injections of DES to unstimulated chicks resulted in a gradual increase in the nuclear content of estradiol receptor, which reached a maximum at 6 days and thereafter declined gradually up to 18 days of hormone treatment. A maximum number of initiation sites for RNA synthesis was also attained at 4 to 6 days of DES treatment and thereafter declined. When DES was withdrawn after 14 to 18 days of hormone stimulation, the numbers of nuclear estradiol receptor sites and initiation sites for RNA synthesis both declined gradually, reaching half-maximal values in 3 days and approached control values after 7 to 8 days of withdrawal. The increase in the concentration of nuclear estradiol receptor sites and the number of initiation sites for RNA synthesis also showed a close correlation with the dosage of DES administration. Both attained maximum levels at 1.25 mg of DES with a half-maximal value of 0.5 mg. The close correlation between the concentration of nuclear-bound estradiol receptors and the number of initiation sites for RNA synthesis in vivo is at present only a temporal correlation but does raise the possibility that gene transcription in chick oviduct may depend upon the amount of estradiol receptor bound to the target cell nuclei.", "contents": "Effect of estrogen on gene expression in the chick oviduct. Correlation between nuclear-bound estrogen receptor and chromatin initiation site for transcription. The [3H]estradiol exchange assay was used to characterize the nuclear estrogen receptor from the chick oviduct. After diethylstilibestrol (DES) treatment (14 days), the oviduct nuclei contained estrogen receptors that manifested high affinity (Kd = 2 X 10(-9)M) and low capacity binding (4000 to 5000 sites/cell) for estradiol. DES and estradiol competed significantly for [3H]estradiol binding, while testosterone and progesterone were ineffective. These binding sites were found in the oviduct and liver but not in the spleen, kidney, or muscle. Following salt extraction from nuclei, the receptor had a sedimentation coefficient of 4 S when analyzed by centrifugation in high and low salt sucrose density gradients. The [3H]estradiol exchange assay was used to examine the relationships between nuclear-bound receptor and RNA polymerase initiation sites on oviduct chromatin. Within 20 min after a single injection of 2.5 mg of DES to withdrawn chicks, a maximum number of estradiol receptor-binding sites was detected in oviduct nuclei. Within 30 min after DES injection, the total number of RNA initiation sites also increased, reaching 100% of control values. Daily injections of DES to unstimulated chicks resulted in a gradual increase in the nuclear content of estradiol receptor, which reached a maximum at 6 days and thereafter declined gradually up to 18 days of hormone treatment. A maximum number of initiation sites for RNA synthesis was also attained at 4 to 6 days of DES treatment and thereafter declined. When DES was withdrawn after 14 to 18 days of hormone stimulation, the numbers of nuclear estradiol receptor sites and initiation sites for RNA synthesis both declined gradually, reaching half-maximal values in 3 days and approached control values after 7 to 8 days of withdrawal. The increase in the concentration of nuclear estradiol receptor sites and the number of initiation sites for RNA synthesis also showed a close correlation with the dosage of DES administration. Both attained maximum levels at 1.25 mg of DES with a half-maximal value of 0.5 mg. The close correlation between the concentration of nuclear-bound estradiol receptors and the number of initiation sites for RNA synthesis in vivo is at present only a temporal correlation but does raise the possibility that gene transcription in chick oviduct may depend upon the amount of estradiol receptor bound to the target cell nuclei."} {"id": "PMID:173721", "title": "Surface morphology and agglutinability with concanavalin A in normal and transformed murine fibroblasts.", "content": "The surface morphology of attached and suspended normal and transformed fibroblasts has been studied with the scanning electron microscope. Normal murine fibroblasts (3T3) grow in vitro with widely extended leading lamellae. During most parts of the cell cycle the surfaces of these cells are practically free of microvilli. When the cells round up for mitosis, their cell surfaces become adorned with many microvilli. In contrast, simian virus 40-transformed fibroblasts (SV3T3) grow more compact, and their cell surfaces remain smooth throughout the life cycle. When confluent 3T3 and SV3T3 cells are suspended with ethylenediaminetetraacetic acid (EDTA) for agglutination assays, similar differences in surface morphology are found: 3T3 cells always bear many microvilli, whereas most SV3T3 cells are essentially free of microvilli. The addition of concanavalin A (Con A) does not influence the surface morphology of the suspended cells. The morphological differences described here may be important for the agglutination process of the normal and transformed 3T3 cells, because they affect the real cell surface area and thus the density of Con A-binding sites.", "contents": "Surface morphology and agglutinability with concanavalin A in normal and transformed murine fibroblasts. The surface morphology of attached and suspended normal and transformed fibroblasts has been studied with the scanning electron microscope. Normal murine fibroblasts (3T3) grow in vitro with widely extended leading lamellae. During most parts of the cell cycle the surfaces of these cells are practically free of microvilli. When the cells round up for mitosis, their cell surfaces become adorned with many microvilli. In contrast, simian virus 40-transformed fibroblasts (SV3T3) grow more compact, and their cell surfaces remain smooth throughout the life cycle. When confluent 3T3 and SV3T3 cells are suspended with ethylenediaminetetraacetic acid (EDTA) for agglutination assays, similar differences in surface morphology are found: 3T3 cells always bear many microvilli, whereas most SV3T3 cells are essentially free of microvilli. The addition of concanavalin A (Con A) does not influence the surface morphology of the suspended cells. The morphological differences described here may be important for the agglutination process of the normal and transformed 3T3 cells, because they affect the real cell surface area and thus the density of Con A-binding sites."} {"id": "PMID:173722", "title": "Characterization of nuclear membranes and endoplasmic reticulum isolated from plant tissue.", "content": "Nuclei, nuclear membranes and rough endoplasmic reticulum (rER) were isolated from onion root tips and stems. Structural preservation and purity of the fractions was determined by electron microscopic and biochemical methods. Gross compositional data (protein, phospholipid, nonpolar lipids, sterols, RNA, DNA), phospholipid and fatty acid patterns, enzyme activities (ATPases, ADPase, IDPase, glucose-6-phosphatase, 5'-nucleotidase, acid phosphatase, and NADH- and NADPH-cytochrome C reductases), and cytochrome contents were determined. A stable, high salt-resistant attachment of some DNA with the nuclear membrane was observed as well as the association of some RNA with high salt-treated nuclear and rER membranes. The phospholipid pattern was identical for both nuclear and rER membranes and showed a predominance of lecithin (about 60%) and phosphatidyl ethanolamine (20-24%). Special care was necessary to minimize lipid degradation by phospholipases during isolations. Nonpolar lipids, mostly sterols and triglycerides, accounted for 35-45% of the membrane lipids. Sterol contents were relatively high in both membrane fractions (molar ratios of sterols to phospholipids ranged from 0.12 to 0.43). Sitosterol accounted for about 80% of the total sterols. Palmitic, oleic, and linoleic acids were the most prevalent acids in membrane-bound lipids as well as in storage lipids and occurred in similar proportions in phospholipids, triglycerides and free fatty acids of the membrane. About 80% of the fatty acids in membrane phospholipids and triglycerides were unsaturated. A cytochrome of the b5 type was characterized in these membranes, but P-450-like cytochromes could not be detected. Both NADH and NADPH-cytochrome c reductases were found in nuclear and rER membranes and appeared to be enriched in rER membranes. Among the phosphatases, Mg2+-ATPase and, to lesser extents, ADPase, IDPase and acid phosphatase activities occurred in the fractions, but significant amounts of monovalent ion-stimulated ATPase, 5'-nucleotidase and glucose-6-phosphatase activities did not. The results obtained emphasize that the close biochemical similarities noted between rER and nuclear membranes of animal cells extend to these fractions from plant cells.", "contents": "Characterization of nuclear membranes and endoplasmic reticulum isolated from plant tissue. Nuclei, nuclear membranes and rough endoplasmic reticulum (rER) were isolated from onion root tips and stems. Structural preservation and purity of the fractions was determined by electron microscopic and biochemical methods. Gross compositional data (protein, phospholipid, nonpolar lipids, sterols, RNA, DNA), phospholipid and fatty acid patterns, enzyme activities (ATPases, ADPase, IDPase, glucose-6-phosphatase, 5'-nucleotidase, acid phosphatase, and NADH- and NADPH-cytochrome C reductases), and cytochrome contents were determined. A stable, high salt-resistant attachment of some DNA with the nuclear membrane was observed as well as the association of some RNA with high salt-treated nuclear and rER membranes. The phospholipid pattern was identical for both nuclear and rER membranes and showed a predominance of lecithin (about 60%) and phosphatidyl ethanolamine (20-24%). Special care was necessary to minimize lipid degradation by phospholipases during isolations. Nonpolar lipids, mostly sterols and triglycerides, accounted for 35-45% of the membrane lipids. Sterol contents were relatively high in both membrane fractions (molar ratios of sterols to phospholipids ranged from 0.12 to 0.43). Sitosterol accounted for about 80% of the total sterols. Palmitic, oleic, and linoleic acids were the most prevalent acids in membrane-bound lipids as well as in storage lipids and occurred in similar proportions in phospholipids, triglycerides and free fatty acids of the membrane. About 80% of the fatty acids in membrane phospholipids and triglycerides were unsaturated. A cytochrome of the b5 type was characterized in these membranes, but P-450-like cytochromes could not be detected. Both NADH and NADPH-cytochrome c reductases were found in nuclear and rER membranes and appeared to be enriched in rER membranes. Among the phosphatases, Mg2+-ATPase and, to lesser extents, ADPase, IDPase and acid phosphatase activities occurred in the fractions, but significant amounts of monovalent ion-stimulated ATPase, 5'-nucleotidase and glucose-6-phosphatase activities did not. The results obtained emphasize that the close biochemical similarities noted between rER and nuclear membranes of animal cells extend to these fractions from plant cells."} {"id": "PMID:173723", "title": "Lanthanum: inhibition of ACTH-stimulated cyclic AMP and corticosterone synthesis in isolated rat adrenocortical cells.", "content": "Lanthanum (La+++) is a well-known Ca++ antagonist in a number of biological systems. It was used in the present study to examine the role of Ca++ in the regulation of adenyl cyclase of the adrenal cortex by ACTH. In micromolar concentrations, .La+++ inhibited both cyclic AMP and corticosterone response of isolated adrenal cortex cells to ACTH. However, a number of intracellular processes were not affected by La+++. These include the stimulation of steroidogenesis by dibutyryl cyclic AMP, conversion of several steroid precursors into corticosterone, and stimulation of the latter by glucose. Thus, inhibition of steroidogenesis by La+++ appears to be solely due to an inhibition of ACTH-stimulated cyclic AMP formation. Electron microscope examination showed that La+++ was localized on plasma membrane of the cells and did not appear to penetrate beyond this region. Since La+++ is believed to replace Ca++ at superficial binding sites on the cell membrane, it is proposed that Ca++ at these sites plays an important role in the regulation of adenyl cyclase by ACTH. Similarities in the role of Ca++ in \"excitation-contraction\" coupling and in the ACTH-adenyl cyclase system raise the possibility that a contractile protein may be involved in the regulation of adenyl cyclase by those hormones which are known to require Ca++ in the process.", "contents": "Lanthanum: inhibition of ACTH-stimulated cyclic AMP and corticosterone synthesis in isolated rat adrenocortical cells. Lanthanum (La+++) is a well-known Ca++ antagonist in a number of biological systems. It was used in the present study to examine the role of Ca++ in the regulation of adenyl cyclase of the adrenal cortex by ACTH. In micromolar concentrations, .La+++ inhibited both cyclic AMP and corticosterone response of isolated adrenal cortex cells to ACTH. However, a number of intracellular processes were not affected by La+++. These include the stimulation of steroidogenesis by dibutyryl cyclic AMP, conversion of several steroid precursors into corticosterone, and stimulation of the latter by glucose. Thus, inhibition of steroidogenesis by La+++ appears to be solely due to an inhibition of ACTH-stimulated cyclic AMP formation. Electron microscope examination showed that La+++ was localized on plasma membrane of the cells and did not appear to penetrate beyond this region. Since La+++ is believed to replace Ca++ at superficial binding sites on the cell membrane, it is proposed that Ca++ at these sites plays an important role in the regulation of adenyl cyclase by ACTH. Similarities in the role of Ca++ in \"excitation-contraction\" coupling and in the ACTH-adenyl cyclase system raise the possibility that a contractile protein may be involved in the regulation of adenyl cyclase by those hormones which are known to require Ca++ in the process."} {"id": "PMID:173724", "title": "Morphological changes in the neuritic growth cone and target neuron during synaptic junction development in culture.", "content": "Our object was to characterize the morphological changes occurring in pre- and postsynaptic elements during their initial contact and subsequent maturation into typical synaptic profiles. Neurons from superior cervical ganglia (SCG) of perinatal rats were freed of their supporting cells and established as isolated cells in culture. To these were added explants of embryonic rat thoracic spinal cord to allow interaction between outgrowing cord neurites and the isolated autonomic neurons. Time of initial contact was assessed by light microscopy; at timed intervals thereafter, cultures were fixed for electron microscopy. Upon contact, growth cone filopodia became extensively applied to the SCG neuronal plasmalemma and manifested numerous punctate regions in which the apposing plasma membranes were separated by only 7-10 nm. The Golgi apparatus of the target neuron hypertrophied, and its production of coated vesicles increased. Similar vesicles were seen in continuity with the SCG plasmalemma near the close contact site; their apparent contribution of a region of postsynaptic membrane with undercoating was considered to be the first definitive sign of synapse formation. Tracer work with peroxidase and ferritin confirmed that the traffic of coated vesicles within the neuronal soma is largely from Golgi region to somal surface. Subsequent to the appearance of postsynaptic density, the form and content of the growth cone was altered by the loss of filopodia and the appearance of synaptic vesicles which gradually became clustered opposite the postsynaptic density. As the synapse matured, synaptic vesicles increased in number, cleft width and content increased, presynaptic density appeared, branched membranous reticulum became greatly diminished, and most lysosomal structures disappeared. Coated vesicles continued to be associated with the postsynaptic membrane at all stages of maturation. The incorporation of Golgi-derived vesicles into discrete regions of the cell membrane could provide the mechanism for confining specific characteristics of the neuronal membrane to the synaptic region.", "contents": "Morphological changes in the neuritic growth cone and target neuron during synaptic junction development in culture. Our object was to characterize the morphological changes occurring in pre- and postsynaptic elements during their initial contact and subsequent maturation into typical synaptic profiles. Neurons from superior cervical ganglia (SCG) of perinatal rats were freed of their supporting cells and established as isolated cells in culture. To these were added explants of embryonic rat thoracic spinal cord to allow interaction between outgrowing cord neurites and the isolated autonomic neurons. Time of initial contact was assessed by light microscopy; at timed intervals thereafter, cultures were fixed for electron microscopy. Upon contact, growth cone filopodia became extensively applied to the SCG neuronal plasmalemma and manifested numerous punctate regions in which the apposing plasma membranes were separated by only 7-10 nm. The Golgi apparatus of the target neuron hypertrophied, and its production of coated vesicles increased. Similar vesicles were seen in continuity with the SCG plasmalemma near the close contact site; their apparent contribution of a region of postsynaptic membrane with undercoating was considered to be the first definitive sign of synapse formation. Tracer work with peroxidase and ferritin confirmed that the traffic of coated vesicles within the neuronal soma is largely from Golgi region to somal surface. Subsequent to the appearance of postsynaptic density, the form and content of the growth cone was altered by the loss of filopodia and the appearance of synaptic vesicles which gradually became clustered opposite the postsynaptic density. As the synapse matured, synaptic vesicles increased in number, cleft width and content increased, presynaptic density appeared, branched membranous reticulum became greatly diminished, and most lysosomal structures disappeared. Coated vesicles continued to be associated with the postsynaptic membrane at all stages of maturation. The incorporation of Golgi-derived vesicles into discrete regions of the cell membrane could provide the mechanism for confining specific characteristics of the neuronal membrane to the synaptic region."} {"id": "PMID:173725", "title": "Rapid breakdown of diphosphoinositide and triphosphoinositide in erythrocyte membranes.", "content": "Incubation of rabbit erythrocytes with 32Pi resulted in labeling of membrane diphosphoinositide, triphosphoinositide, and phosphatidic acid. Hypotonic lysis at 37 degress C resulted in an extremely rapid breakdown of the labeled polyphosphoinositides. This breakdown could be retarded by lysis in the presence of EDTA and by lowering the temperature to 0 degrees thus allowing preparation of membranes with minimum breakdown of the labeled lipids. Rapid breakdown of di- and triphosphoinositide in isolated membranes could be initiated by Ca++ or to a lesser extent by Mg++ and prevented by detergents and by heating to 75 degrees C. Assay of radiolabeled lipid was carried out by a method which bypassed prior lipid extraction and which enabled sequential sampling of reactions at 10-second intervals. This method was more convenient than standard procedures and gave yields of di- and triphosphoinositide equivalent to that obtained by the method of Folch.", "contents": "Rapid breakdown of diphosphoinositide and triphosphoinositide in erythrocyte membranes. Incubation of rabbit erythrocytes with 32Pi resulted in labeling of membrane diphosphoinositide, triphosphoinositide, and phosphatidic acid. Hypotonic lysis at 37 degress C resulted in an extremely rapid breakdown of the labeled polyphosphoinositides. This breakdown could be retarded by lysis in the presence of EDTA and by lowering the temperature to 0 degrees thus allowing preparation of membranes with minimum breakdown of the labeled lipids. Rapid breakdown of di- and triphosphoinositide in isolated membranes could be initiated by Ca++ or to a lesser extent by Mg++ and prevented by detergents and by heating to 75 degrees C. Assay of radiolabeled lipid was carried out by a method which bypassed prior lipid extraction and which enabled sequential sampling of reactions at 10-second intervals. This method was more convenient than standard procedures and gave yields of di- and triphosphoinositide equivalent to that obtained by the method of Folch."} {"id": "PMID:173726", "title": "Light-microscopic observations of individual microtubules reconstituted from brain tubulin.", "content": "The course of polymerization of individual brain microtubules could be observed with a light microscope employing dark-field illumination. Statistical analysis of the increase in microtubule length during the polymerization was in accordance with the time course of viscosity change of the tubulin solution. After a plateau level in viscosity was attained, there was no significant change in histograms showing length distribution. These observations were confirmed with fixed and stained microtubules, using a phase-contrast microscope. Observations with dark-field illumination revealed that reconstituted microtubules depolymerized and disappeared immediately upon exposure to buffer containing CaCl2 or sulphydryl reagents such as p-chloromercuriphenyl sulphonic acid (PCMPS) and p-chloromercuribenzoic acid (PCMB). They were also cold-labile. The growth of heterogeneous microtubules which were assembled by mixing purified tubulin dimers with ciliary outer fibres could also be followed with these optical systems.", "contents": "Light-microscopic observations of individual microtubules reconstituted from brain tubulin. The course of polymerization of individual brain microtubules could be observed with a light microscope employing dark-field illumination. Statistical analysis of the increase in microtubule length during the polymerization was in accordance with the time course of viscosity change of the tubulin solution. After a plateau level in viscosity was attained, there was no significant change in histograms showing length distribution. These observations were confirmed with fixed and stained microtubules, using a phase-contrast microscope. Observations with dark-field illumination revealed that reconstituted microtubules depolymerized and disappeared immediately upon exposure to buffer containing CaCl2 or sulphydryl reagents such as p-chloromercuriphenyl sulphonic acid (PCMPS) and p-chloromercuribenzoic acid (PCMB). They were also cold-labile. The growth of heterogeneous microtubules which were assembled by mixing purified tubulin dimers with ciliary outer fibres could also be followed with these optical systems."} {"id": "PMID:173727", "title": "Trypsinized BHK21 cells aggregate in the presence of metabolic inhibitors and in the absence of divalent cations.", "content": "The rapid formation of adhesions in suspension by lightly trypsinized BHK21 cells is not dependent on protein synthesis, and only in part on cellular metabolism, although it is completely inhibited by heat- and aldehyde-fixation of the cells. A requirement for protein synthesis becomes evident only if cells are exposed to high levels of trypsin for long periods. Formation of adhesions does not require addition to the medium of divalent cations, although it is increased by divalent manganese and cobalt ions. It is promoted by cytochalasin B and by cyclic AMP and is not inhibited by p-mercuriphenylsulphonate. We discuss a possible relationship between aggregation and the formation of gap junctions.", "contents": "Trypsinized BHK21 cells aggregate in the presence of metabolic inhibitors and in the absence of divalent cations. The rapid formation of adhesions in suspension by lightly trypsinized BHK21 cells is not dependent on protein synthesis, and only in part on cellular metabolism, although it is completely inhibited by heat- and aldehyde-fixation of the cells. A requirement for protein synthesis becomes evident only if cells are exposed to high levels of trypsin for long periods. Formation of adhesions does not require addition to the medium of divalent cations, although it is increased by divalent manganese and cobalt ions. It is promoted by cytochalasin B and by cyclic AMP and is not inhibited by p-mercuriphenylsulphonate. We discuss a possible relationship between aggregation and the formation of gap junctions."} {"id": "PMID:173728", "title": "[Determination of vitamin D3 and its isomers in D3 resins and in mixtures with vitamin A acetate (author's transl)].", "content": "Vitamin D3 and its isomers, prepared from 7-dehydrocholesterol by photochemical reaction, can be separated and quantitatively determined by high-pressure liquid chromatography on aluminium oxide using chloroform as the eluting agent. The determination of small amounts of vitamin D3 in an excess of vitamin A acetate can be achieved by the same method.", "contents": "[Determination of vitamin D3 and its isomers in D3 resins and in mixtures with vitamin A acetate (author's transl)]. Vitamin D3 and its isomers, prepared from 7-dehydrocholesterol by photochemical reaction, can be separated and quantitatively determined by high-pressure liquid chromatography on aluminium oxide using chloroform as the eluting agent. The determination of small amounts of vitamin D3 in an excess of vitamin A acetate can be achieved by the same method."} {"id": "PMID:173729", "title": "Specific thin-layer chromatographic method for the determination of theophylline in plasma in the presence of some other drugs.", "content": "A simple spectrodensitometric method for the direct determination of theophylline was developed from measurement of the absorbance of the compound on silica gel layers irradiated at 275 nm. Auantities as low as 0.010 mug can be detected and a linear relationship was obtained between peak area and the amount of the drug in the spots from 0.025-0.200 mug. The recovery over the usual range of plasma concentration (2.5-20 mug/ml) was 95-107%. The method is sufficiently sensitive and specific for clinical purposes and the time for the assay is about 2 h. Caffeine, frequently present in human plasma, was well separated from theophylline at all concentration levels as were several other drugs commonly used in respiratory problems.", "contents": "Specific thin-layer chromatographic method for the determination of theophylline in plasma in the presence of some other drugs. A simple spectrodensitometric method for the direct determination of theophylline was developed from measurement of the absorbance of the compound on silica gel layers irradiated at 275 nm. Auantities as low as 0.010 mug can be detected and a linear relationship was obtained between peak area and the amount of the drug in the spots from 0.025-0.200 mug. The recovery over the usual range of plasma concentration (2.5-20 mug/ml) was 95-107%. The method is sufficiently sensitive and specific for clinical purposes and the time for the assay is about 2 h. Caffeine, frequently present in human plasma, was well separated from theophylline at all concentration levels as were several other drugs commonly used in respiratory problems."} {"id": "PMID:173730", "title": "The separation by thin-layer chromatography of trace metals as their tetraphenylporphyrin chelates.", "content": "The tetraphenylporphyrin chelates of iron, cobalt, manganese, nickel, zinc, copper, rhodium lead, cadmium and mercury were prepared and their chromatographic behaviour investigated using four different adsorbents and eleven different solvent systems. Mixtures of lead, cadmium and mercury chelates exhibited isographic behaviour in all conditions; mixtures of the other metal chelates were adequately resolved on silica (MN Polygram Sil SHR) by the solvent system light petroleum (b.p. 80-100 degrees)-toluene-acetic acid-water (66:33:85:15, v/v, upper phase). The intense colours of the chelates permit their visual detection at levels of about 10(-10) moles; using the integrated ion-current mass spectrometric procedure, as little as 10(-14) moles of metal could be detected and assessed.", "contents": "The separation by thin-layer chromatography of trace metals as their tetraphenylporphyrin chelates. The tetraphenylporphyrin chelates of iron, cobalt, manganese, nickel, zinc, copper, rhodium lead, cadmium and mercury were prepared and their chromatographic behaviour investigated using four different adsorbents and eleven different solvent systems. Mixtures of lead, cadmium and mercury chelates exhibited isographic behaviour in all conditions; mixtures of the other metal chelates were adequately resolved on silica (MN Polygram Sil SHR) by the solvent system light petroleum (b.p. 80-100 degrees)-toluene-acetic acid-water (66:33:85:15, v/v, upper phase). The intense colours of the chelates permit their visual detection at levels of about 10(-10) moles; using the integrated ion-current mass spectrometric procedure, as little as 10(-14) moles of metal could be detected and assessed."} {"id": "PMID:173732", "title": "Separation of C27, C28 and C29 sterols by reversed-phase high-performance liquid chromatography on small particles.", "content": "The application of reversed-phase high-performance liquid chromatography to the analytical- and preparative-scale separation of sterols has been evaluated. The capacity factors, k', for a number of compounds chromatographed on a muBondapak C18 (LESS THAN 10 MUM) COLUMN ARE PRESENTED. C27, C28 and C29 sterols and also sterols differing in degree of unsaturation could be readily separated as their acetates in this system. The present reversed-phase chromatographic method is apparently not as selective as silver nitrate-silica gel thin-layer chromatography for the position of unsaturation in the sterol molecule.", "contents": "Separation of C27, C28 and C29 sterols by reversed-phase high-performance liquid chromatography on small particles. The application of reversed-phase high-performance liquid chromatography to the analytical- and preparative-scale separation of sterols has been evaluated. The capacity factors, k', for a number of compounds chromatographed on a muBondapak C18 (LESS THAN 10 MUM) COLUMN ARE PRESENTED. C27, C28 and C29 sterols and also sterols differing in degree of unsaturation could be readily separated as their acetates in this system. The present reversed-phase chromatographic method is apparently not as selective as silver nitrate-silica gel thin-layer chromatography for the position of unsaturation in the sterol molecule."} {"id": "PMID:173733", "title": "High-speed liquid chromatography of polychlorinated biphenyls and related compounds.", "content": "High-speed liquid chromatography in the system silica gel-dry n-hexane has been used to characterize the behaviour of a series of commercially available mixtures of chlorinated biphenyls, viz., Aroclor 1221-1268. An attempt has been made to assign a large number of peaks in the chromatograms of the Aroclors to the individual constituents. To this end, retention times and UV spectra were recorded for 47 polychlorinated biphenyls. The dependence of retention and spectral characteristics on the chlorine content of the substituted biphenyls is discussed", "contents": "High-speed liquid chromatography of polychlorinated biphenyls and related compounds. High-speed liquid chromatography in the system silica gel-dry n-hexane has been used to characterize the behaviour of a series of commercially available mixtures of chlorinated biphenyls, viz., Aroclor 1221-1268. An attempt has been made to assign a large number of peaks in the chromatograms of the Aroclors to the individual constituents. To this end, retention times and UV spectra were recorded for 47 polychlorinated biphenyls. The dependence of retention and spectral characteristics on the chlorine content of the substituted biphenyls is discussed"} {"id": "PMID:173735", "title": "Plasma levels of beta-MSH and ACTH during acute stresses and metyrapone administration in man.", "content": "Simultaneous measurements of both beta-melanocyte stimulating hormone (beta-MSH) and adrenocorticotropic hormone (ACTH) in extracted plasma were performed by specific radioimmunoassays. During insulin-induced hypoglycemia, there was a marked increase of plasma ACTH levels and a slight but significant increase of plasma beta-MSH levels. Lysine-vasopressin on the other hand, caused a significant rise of plasma ACTH levels without corresponding response of plasma beta-MSH. Following glucagon administration, neither hormone rose significantly. However, metyrapone infusion caused a significant increase of both ACTH and beta-MSH levels, and frequent blood sampling revealed that both hormones were secreted episodically, and that peaks generally coincided with each other. These data suggest that the secretion of these two hormones can occur together in most instances, and that the same mechanism is involved in the secretion of both hormones under the negative feedback control.", "contents": "Plasma levels of beta-MSH and ACTH during acute stresses and metyrapone administration in man. Simultaneous measurements of both beta-melanocyte stimulating hormone (beta-MSH) and adrenocorticotropic hormone (ACTH) in extracted plasma were performed by specific radioimmunoassays. During insulin-induced hypoglycemia, there was a marked increase of plasma ACTH levels and a slight but significant increase of plasma beta-MSH levels. Lysine-vasopressin on the other hand, caused a significant rise of plasma ACTH levels without corresponding response of plasma beta-MSH. Following glucagon administration, neither hormone rose significantly. However, metyrapone infusion caused a significant increase of both ACTH and beta-MSH levels, and frequent blood sampling revealed that both hormones were secreted episodically, and that peaks generally coincided with each other. These data suggest that the secretion of these two hormones can occur together in most instances, and that the same mechanism is involved in the secretion of both hormones under the negative feedback control."} {"id": "PMID:173736", "title": "Calcium and folic acid absorption in patients taking anticonvulsant drugs.", "content": "Calcium and folic acid absorption were studied in 28 adult male epileptics on chronic anticonvulsant therapy. In 16 patients on diphenylhydantoin alone, calcium absorption was abnormal in 9. In 12 patients on both diphenylhydantoin and phenobarbital, calcium absorption was abnormal in 3 patients. Folic acid (3H-PGA) absorption was normal in all but one patient, while serum folate (less than 6.4 ng/ml) was reduced in all patients. Hypocalcemia (less than 8.5 mg/100 ml) occurred in only 2 patients, while serum alkaline phosphatase was elevated in 7 patients. These findings support the proposal that rickets and osteomalacia reported in patients on chronic anticonvulsant therapy results from reduced calcium absorption. The effect of these drugs appears to be the acceleration of the metabolism of vitamin D and an increase in the excretion of polar metabolites. This may result in reduced levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol which are necessary for normal absorption of calcium. Since calcium absorption may be impaired secondary to a relative vitamin D deficiency, a supplemental increase in vitamin D intake by patients on anticonvulsant drugs is recommended.", "contents": "Calcium and folic acid absorption in patients taking anticonvulsant drugs. Calcium and folic acid absorption were studied in 28 adult male epileptics on chronic anticonvulsant therapy. In 16 patients on diphenylhydantoin alone, calcium absorption was abnormal in 9. In 12 patients on both diphenylhydantoin and phenobarbital, calcium absorption was abnormal in 3 patients. Folic acid (3H-PGA) absorption was normal in all but one patient, while serum folate (less than 6.4 ng/ml) was reduced in all patients. Hypocalcemia (less than 8.5 mg/100 ml) occurred in only 2 patients, while serum alkaline phosphatase was elevated in 7 patients. These findings support the proposal that rickets and osteomalacia reported in patients on chronic anticonvulsant therapy results from reduced calcium absorption. The effect of these drugs appears to be the acceleration of the metabolism of vitamin D and an increase in the excretion of polar metabolites. This may result in reduced levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol which are necessary for normal absorption of calcium. Since calcium absorption may be impaired secondary to a relative vitamin D deficiency, a supplemental increase in vitamin D intake by patients on anticonvulsant drugs is recommended."} {"id": "PMID:173737", "title": "Sensitivity of infectious bovine rhinotracheitis virus to ether.", "content": "The sensitivity of 12 field isolates of infectious boviine rhinotracheitis (IBR) virus and four commercial modified-live infectious bovine rhinotracheitis virus vaccine strains was determined after exposure to 20% ethyl ether (anesthetic) for 16 h at 4 c. The infectivity of five field strains was reduced by varying degrees, whereas seven were found to be resistant. Three vaccine strains were moderately sensitive, and one strain was resistant. Four of the sensitive field strains were isolated from the conjunctiva and the other was isolated from the surface of the epiglottis of natural infective cattle. Strains of virus isolated from fetal tissue and nasal cavity were resistant. All viruses were readily inactivated by chloroform treatment.", "contents": "Sensitivity of infectious bovine rhinotracheitis virus to ether. The sensitivity of 12 field isolates of infectious boviine rhinotracheitis (IBR) virus and four commercial modified-live infectious bovine rhinotracheitis virus vaccine strains was determined after exposure to 20% ethyl ether (anesthetic) for 16 h at 4 c. The infectivity of five field strains was reduced by varying degrees, whereas seven were found to be resistant. Three vaccine strains were moderately sensitive, and one strain was resistant. Four of the sensitive field strains were isolated from the conjunctiva and the other was isolated from the surface of the epiglottis of natural infective cattle. Strains of virus isolated from fetal tissue and nasal cavity were resistant. All viruses were readily inactivated by chloroform treatment."} {"id": "PMID:173738", "title": "Epidemiologic study of a leukocyte-transforming agent in a general population.", "content": "Studies by others have demonstrated a leukocyte-transforming agent(s) (LTA) in the oropharyngeal secretions of a significant number of individuals with Epstein-Barr virus-associated infectious mononucleosis, cancer, and, to a lesser extent, an outpatient population. This present study determines by systematic sampling the prevalence of LTA in 27 families of a semirural community. Throat swab inoculums from three of 54 adults and none of 44 children induced transformation of umbilical cord lymphocytes. Complement-dependent Epstein-Barr virus nuclear antigen was detected in two of the three transformed cell cultures. The three LTA-positive individuals were characterized by the absence of serologic evidence of a recent Epstein-Barr virus infection and the lack of elevated antibodies against the viral capsid antigen of Epstein-Barr virus.", "contents": "Epidemiologic study of a leukocyte-transforming agent in a general population. Studies by others have demonstrated a leukocyte-transforming agent(s) (LTA) in the oropharyngeal secretions of a significant number of individuals with Epstein-Barr virus-associated infectious mononucleosis, cancer, and, to a lesser extent, an outpatient population. This present study determines by systematic sampling the prevalence of LTA in 27 families of a semirural community. Throat swab inoculums from three of 54 adults and none of 44 children induced transformation of umbilical cord lymphocytes. Complement-dependent Epstein-Barr virus nuclear antigen was detected in two of the three transformed cell cultures. The three LTA-positive individuals were characterized by the absence of serologic evidence of a recent Epstein-Barr virus infection and the lack of elevated antibodies against the viral capsid antigen of Epstein-Barr virus."} {"id": "PMID:173739", "title": "Intrinsic mineralocorticoid agonist activity of some nonsteroidal anti-inflammatory drugs. A postulated mechanism for sodium retention.", "content": "Because some nonsteroidal anti-inflammatory drugs (NSAID) induce salt and water retention and exhibit other steroid-like actions, studies were performed to ascertain whether these drugs possess intrinsic mineralocorticoid agonist activity. In vitro competitive binding assays utilizing tissue from adrenalectomized rats demonstrated that some NSAID can displace [3H]-aldosterone from renal cytoplasmic mineralocorticoid receptors. Displacement potency for these sites was in the sequence: aldosterone greater than spironolactone greater than phenylbutazone (PBZ) greater than aspirin (ASA) greater than indomethacin (IDM). Concentration ratios required to obtain significant displacement of [3H]aldosterone were high but clearly within the therapeutic range for PBZ and ASA but not IDM. The analogues oxyphenbutazone (OBZ) and sodium salicylate (SS) were similar in binding activity to PBZ and ASA, respectively. Lineweaver-Burk analysis revealed that the inhibition of [3H]aldosterone binding was competitive in nature. In addition, PBZ was shown to prevent the nuclear binding of [3H]aldosterone. In vivo injection of PBZ and ASA resulted in competition for [3H]aldosterone renal binding comparable to the in vitro studies. Administration of PBZ and OBZ to adrenalectomized rats resulted in significant salt retention whereas ASA and SS did not differ significantly from controls. Salt retention elicited by PBZ and OBZ was inhibited by spironolactone, a competitive mineralocorticoid antagonist. These data suggest that, despite nonsteroidal structures, PBZ and OBZ induce salt retention via a receptor-mediated mineralocorticoid pathway analogous to aldosterone action.", "contents": "Intrinsic mineralocorticoid agonist activity of some nonsteroidal anti-inflammatory drugs. A postulated mechanism for sodium retention. Because some nonsteroidal anti-inflammatory drugs (NSAID) induce salt and water retention and exhibit other steroid-like actions, studies were performed to ascertain whether these drugs possess intrinsic mineralocorticoid agonist activity. In vitro competitive binding assays utilizing tissue from adrenalectomized rats demonstrated that some NSAID can displace [3H]-aldosterone from renal cytoplasmic mineralocorticoid receptors. Displacement potency for these sites was in the sequence: aldosterone greater than spironolactone greater than phenylbutazone (PBZ) greater than aspirin (ASA) greater than indomethacin (IDM). Concentration ratios required to obtain significant displacement of [3H]aldosterone were high but clearly within the therapeutic range for PBZ and ASA but not IDM. The analogues oxyphenbutazone (OBZ) and sodium salicylate (SS) were similar in binding activity to PBZ and ASA, respectively. Lineweaver-Burk analysis revealed that the inhibition of [3H]aldosterone binding was competitive in nature. In addition, PBZ was shown to prevent the nuclear binding of [3H]aldosterone. In vivo injection of PBZ and ASA resulted in competition for [3H]aldosterone renal binding comparable to the in vitro studies. Administration of PBZ and OBZ to adrenalectomized rats resulted in significant salt retention whereas ASA and SS did not differ significantly from controls. Salt retention elicited by PBZ and OBZ was inhibited by spironolactone, a competitive mineralocorticoid antagonist. These data suggest that, despite nonsteroidal structures, PBZ and OBZ induce salt retention via a receptor-mediated mineralocorticoid pathway analogous to aldosterone action."} {"id": "PMID:173740", "title": "Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.", "content": "The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo old, fixed in OSO4, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [alpha-32P] ATP as substrate and expressed as cyclic [32P] AMP/10 min per mg protein or per 10(6) cells. Enzyme activity was determined for the basal state and in the presence of varying concentrations of glucagon, ACTH, epinephrine, and fluoride. Basal activity per cell increased in threefold between 1 and 2 mo with a comparable increase in cell surface area, suggesting synthesis of enzyme along with new cell membrane. Although epinephrine stimulated adenylate cyclase 8-fold and fluoride 12-fold throughout the life-span of the rat, stimulated activity paralleled basal levels, decreasing 60% between 2 and 24 mo per mg protein and 40% between 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal- and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH)P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH) P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes.", "contents": "Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging. The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo old, fixed in OSO4, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [alpha-32P] ATP as substrate and expressed as cyclic [32P] AMP/10 min per mg protein or per 10(6) cells. Enzyme activity was determined for the basal state and in the presence of varying concentrations of glucagon, ACTH, epinephrine, and fluoride. Basal activity per cell increased in threefold between 1 and 2 mo with a comparable increase in cell surface area, suggesting synthesis of enzyme along with new cell membrane. Although epinephrine stimulated adenylate cyclase 8-fold and fluoride 12-fold throughout the life-span of the rat, stimulated activity paralleled basal levels, decreasing 60% between 2 and 24 mo per mg protein and 40% between 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal- and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH)P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH) P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes."} {"id": "PMID:173742", "title": "Potentiation of erythropoiesis in vitro by dexamethasone.", "content": "The effect of dexamethasone on erythropoiesis was examined in vitro. Hematopoietic cells from 13-day mouse fetal livers were cultured for 48 h in the presence or absence of erythropoietin and erythroid colonies enumerated. Colony formation occurring in cultures containing no added erythropoietin was inhibited by the incorporation of antierythropoietin antibody, suggesting that these colonies formed in response to endogenous hepatic erythropoietin. Maximal colony formation was observed with 0.5 U/ml of sheep erythropoietin. Dexamethasone increased erythroid colony formation with peak stimulation at 10(-9) M. Dexamethasone potentiation was most marked in cultures containing less than maximally stimulating concentrations of erythropoietin. The cells required only a brief exposure to glucocorticosteroid to exhibit the augmented cloning capacity, and dexamethasone stimulation was inhibited by progesterone (10(-6) M). A comparable response to dexamethasone was observed in cultures of adult murine and human bone marrow erythroid progenitors, implying that the phenomenon is not peculiar to fetal cells and is not dependent on the presence of fetal hepatocytes. These data suggest that erythroid progenitor cells possess a glucocorticoid receptor mechanism that can modulate the response to erythropoietin in vitro.", "contents": "Potentiation of erythropoiesis in vitro by dexamethasone. The effect of dexamethasone on erythropoiesis was examined in vitro. Hematopoietic cells from 13-day mouse fetal livers were cultured for 48 h in the presence or absence of erythropoietin and erythroid colonies enumerated. Colony formation occurring in cultures containing no added erythropoietin was inhibited by the incorporation of antierythropoietin antibody, suggesting that these colonies formed in response to endogenous hepatic erythropoietin. Maximal colony formation was observed with 0.5 U/ml of sheep erythropoietin. Dexamethasone increased erythroid colony formation with peak stimulation at 10(-9) M. Dexamethasone potentiation was most marked in cultures containing less than maximally stimulating concentrations of erythropoietin. The cells required only a brief exposure to glucocorticosteroid to exhibit the augmented cloning capacity, and dexamethasone stimulation was inhibited by progesterone (10(-6) M). A comparable response to dexamethasone was observed in cultures of adult murine and human bone marrow erythroid progenitors, implying that the phenomenon is not peculiar to fetal cells and is not dependent on the presence of fetal hepatocytes. These data suggest that erythroid progenitor cells possess a glucocorticoid receptor mechanism that can modulate the response to erythropoietin in vitro."} {"id": "PMID:173741", "title": "Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.", "content": "The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of 125 I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro) insulin in this system. In all conditions tested, the incorporation of [3H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM) activated six- to sevenfold the [3H]leucine incorporation into IRI. Theophylline or N6O2-dibutyryl- (db) cAMP at 1.6 mM glucose significantly increased the [3H]leucine incorporation. Glucose at 16.7 mM further enhanced the effect of both drugs. Contrarily, somatostatin (1-10 mug/ml) inhibits the rate of [3H]leucine incorporation into IRI in the presence of 11 mM glucose; this effect was observed at 5.5 mM glucose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca++ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucose-induced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 muM) AND TOLBUTAMIDE (400 MUM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [3H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas. These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMP-induced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has to be considered in the use of these agents in human disease.", "contents": "Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin. The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of 125 I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro) insulin in this system. In all conditions tested, the incorporation of [3H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM) activated six- to sevenfold the [3H]leucine incorporation into IRI. Theophylline or N6O2-dibutyryl- (db) cAMP at 1.6 mM glucose significantly increased the [3H]leucine incorporation. Glucose at 16.7 mM further enhanced the effect of both drugs. Contrarily, somatostatin (1-10 mug/ml) inhibits the rate of [3H]leucine incorporation into IRI in the presence of 11 mM glucose; this effect was observed at 5.5 mM glucose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca++ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucose-induced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 muM) AND TOLBUTAMIDE (400 MUM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [3H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas. These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMP-induced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has to be considered in the use of these agents in human disease."} {"id": "PMID:173743", "title": "Metabolism and biological activity of parathyroid hormone in renal cortical membranes.", "content": "Recent studies from several laboratories have documented the presence of fragments of parathyroid hormone in blood or peripheral tissues or in both. Inasmuch as amino-terminal fragments are known to be biologically active, it has been suggested that fragments, rather than the intact polypeptide of 84 amino acids, might be the active molecular species in tissue fluids. Accordingly, the metabolism of native bovine parathyroid hormone, bPTH-(1-84), was studied in purified renal cortical membranes from several species and correlated with hormonal stimulation of adenylyl cyclase in these membranes in vitro. Analysis of whole incubation mixtures or membrane-bound hormone by gel electrophoresis and gel chromatography after incubation of [3H]bPTH-(1-84) or 125-I-labeled bPTH-(1-84) or unlabeled biologically active bPTH-(1-84) with purified canine renal cortical membranes revealed no evidence of proteolysis, and yet the uncleaved hormone readily stimulated adenylyl cyclase. Kinetic studies of hormone-stimulated adenylyl cyclase activity revealed no difference in rate of onset of activity between bPTH-(1-84) And the active synthetic amino-terminal tetratriacontapeptide bPTH-(1-34), and hence there was no evidence of precursor-product relationship between the native hormone and an active amino-terminal fragment. The results suggest, insofar as the activity detected in these membranes reflects the biological response of the hormone in vivo, that the native hormone is indeed biologically active at the receptor level directly without the requirement for cleavage into active fragments.", "contents": "Metabolism and biological activity of parathyroid hormone in renal cortical membranes. Recent studies from several laboratories have documented the presence of fragments of parathyroid hormone in blood or peripheral tissues or in both. Inasmuch as amino-terminal fragments are known to be biologically active, it has been suggested that fragments, rather than the intact polypeptide of 84 amino acids, might be the active molecular species in tissue fluids. Accordingly, the metabolism of native bovine parathyroid hormone, bPTH-(1-84), was studied in purified renal cortical membranes from several species and correlated with hormonal stimulation of adenylyl cyclase in these membranes in vitro. Analysis of whole incubation mixtures or membrane-bound hormone by gel electrophoresis and gel chromatography after incubation of [3H]bPTH-(1-84) or 125-I-labeled bPTH-(1-84) or unlabeled biologically active bPTH-(1-84) with purified canine renal cortical membranes revealed no evidence of proteolysis, and yet the uncleaved hormone readily stimulated adenylyl cyclase. Kinetic studies of hormone-stimulated adenylyl cyclase activity revealed no difference in rate of onset of activity between bPTH-(1-84) And the active synthetic amino-terminal tetratriacontapeptide bPTH-(1-34), and hence there was no evidence of precursor-product relationship between the native hormone and an active amino-terminal fragment. The results suggest, insofar as the activity detected in these membranes reflects the biological response of the hormone in vivo, that the native hormone is indeed biologically active at the receptor level directly without the requirement for cleavage into active fragments."} {"id": "PMID:173744", "title": "Abnormal properties of collagen lysyl hydroxylase from skin fibroblasts of siblings with hydroxylysine-deficient collagen.", "content": "Skin fibroblasts from two siblings with hydroxylysine-deficient collagen collagen (Ehlers-Danlos syndrome, type VI) contained normal levels of collagen prolyl hydroxylase activity but were markedly deficient in collagen lysyl hydroxylase activity. The deficiency was evident in all fractions of cell lysates, in low and high ionic strength buffers, and in detergent. Assays of mixtures of wild-type and mutant cell lysates indicated no activation of mutant enzyme by factors in wild-type cells or inhibition of normal enzyme by material in mutant cells. Wild type or mutant cells cultured with ascorbic acid (50 mug/ml of culture medium, added daily) contained approximately the same level of lysyl hydroxylase activity as cells cultured without ascorbate, but prolyl hydroxylase activity without ascorbate was depressed in both an average of 41%. The mutant lysyl hydroxylase was less stable at 37 degrees C than the wild type and did not form high molecular weight aggregates in low ionic strength buffers, as did the control enzyme. The activity of the mutant enzyme was maximally stimulated after dialysis against buffer solutions containing 10 mM dithiothreitol. When assayed in 100 muM dithiothreitol, the mutant enzyme exhibited a higher apparent Km for ascorbate (20 muM) than the wild type (4 muM). In 1.0 mM dithiothreitol the mutant enzyme's apparent Km for ascorbate was reduced to 5 muM. Wild type and mutant enzymes had the same apparent Km for alpha-keto-glutarate (20 muM). The properties of prolyl hydroxylase in wild type and mutant cells were identical: apparent Km's for ascorbate and alpha-ketoglutarate were 100 muM and 20 muM, respectively. If mutant enzyme protein with altered kinetic properties is the only enzyme functioning to hydroxylate lysyl residues in collagen, the variations in hydroxylysine content observed in collagen from different tissues in the subjects reported here could be in part due to differences in cofactor concentrations and in rate and sequence of events in collagen synthesis in different tissues.", "contents": "Abnormal properties of collagen lysyl hydroxylase from skin fibroblasts of siblings with hydroxylysine-deficient collagen. Skin fibroblasts from two siblings with hydroxylysine-deficient collagen collagen (Ehlers-Danlos syndrome, type VI) contained normal levels of collagen prolyl hydroxylase activity but were markedly deficient in collagen lysyl hydroxylase activity. The deficiency was evident in all fractions of cell lysates, in low and high ionic strength buffers, and in detergent. Assays of mixtures of wild-type and mutant cell lysates indicated no activation of mutant enzyme by factors in wild-type cells or inhibition of normal enzyme by material in mutant cells. Wild type or mutant cells cultured with ascorbic acid (50 mug/ml of culture medium, added daily) contained approximately the same level of lysyl hydroxylase activity as cells cultured without ascorbate, but prolyl hydroxylase activity without ascorbate was depressed in both an average of 41%. The mutant lysyl hydroxylase was less stable at 37 degrees C than the wild type and did not form high molecular weight aggregates in low ionic strength buffers, as did the control enzyme. The activity of the mutant enzyme was maximally stimulated after dialysis against buffer solutions containing 10 mM dithiothreitol. When assayed in 100 muM dithiothreitol, the mutant enzyme exhibited a higher apparent Km for ascorbate (20 muM) than the wild type (4 muM). In 1.0 mM dithiothreitol the mutant enzyme's apparent Km for ascorbate was reduced to 5 muM. Wild type and mutant enzymes had the same apparent Km for alpha-keto-glutarate (20 muM). The properties of prolyl hydroxylase in wild type and mutant cells were identical: apparent Km's for ascorbate and alpha-ketoglutarate were 100 muM and 20 muM, respectively. If mutant enzyme protein with altered kinetic properties is the only enzyme functioning to hydroxylate lysyl residues in collagen, the variations in hydroxylysine content observed in collagen from different tissues in the subjects reported here could be in part due to differences in cofactor concentrations and in rate and sequence of events in collagen synthesis in different tissues."} {"id": "PMID:173745", "title": "Development and evaluation of porous dental implants in miniature swine.", "content": "Organized bone ingrowth in endosteal porous implants fabricated from VMC titanium alloy and surgically implanted with a tight interference fit, securely anchored the implants in fresh and healed mandibular premolar sites of miniature swine. This bone-implant union retained its integrity under high as well as slight masticatory stresses up to one-year after implantation. Bone invasion of the alumina porcelain implants was impeded by the lack of adequate interconnecting porosity; when the porosity was increased, insufficient ceramic strength prohibited a tight initial bone-implant fit. As a consequence, inadequate initial implant stability resulted in a soft tissue encapsulation of the majority of the ceramic implants. Histological examination and mechanical testing results were similar for bone-ingrown implants exposed to different experimental stresses for 4, 5, 8, and 12 months. Bone ingrowth and interface shear strengths were also similar in the different VMC pore sizes and shapes investigated. The design of intraoral attachments appeared critical, at least in swine where no postoperative treatment was administered. Gingival inflammation and alveolar bone resorption caused by calculus were severe around truncated cone-shaped devices. Slender transgingival posts, occlusal caps, and crown restorations were less susceptible to calculus accumulation, resulting in a more satisfactory gingival and subgingival response. Excessive epithelial invagination was a problem only in implants with transgingival truncated cones. Good adherence of soft tissue to metal under the gingival mucosa prevented epithelial migration around implants with other transgingival devices. Alveolar bone resportion around the tops of bone-ingrown implants was minimal at the time intervals examined (up to one year); however, a definite conclusion should be delayed until longer-term implants under full occlusion are evaluated.", "contents": "Development and evaluation of porous dental implants in miniature swine. Organized bone ingrowth in endosteal porous implants fabricated from VMC titanium alloy and surgically implanted with a tight interference fit, securely anchored the implants in fresh and healed mandibular premolar sites of miniature swine. This bone-implant union retained its integrity under high as well as slight masticatory stresses up to one-year after implantation. Bone invasion of the alumina porcelain implants was impeded by the lack of adequate interconnecting porosity; when the porosity was increased, insufficient ceramic strength prohibited a tight initial bone-implant fit. As a consequence, inadequate initial implant stability resulted in a soft tissue encapsulation of the majority of the ceramic implants. Histological examination and mechanical testing results were similar for bone-ingrown implants exposed to different experimental stresses for 4, 5, 8, and 12 months. Bone ingrowth and interface shear strengths were also similar in the different VMC pore sizes and shapes investigated. The design of intraoral attachments appeared critical, at least in swine where no postoperative treatment was administered. Gingival inflammation and alveolar bone resorption caused by calculus were severe around truncated cone-shaped devices. Slender transgingival posts, occlusal caps, and crown restorations were less susceptible to calculus accumulation, resulting in a more satisfactory gingival and subgingival response. Excessive epithelial invagination was a problem only in implants with transgingival truncated cones. Good adherence of soft tissue to metal under the gingival mucosa prevented epithelial migration around implants with other transgingival devices. Alveolar bone resportion around the tops of bone-ingrown implants was minimal at the time intervals examined (up to one year); however, a definite conclusion should be delayed until longer-term implants under full occlusion are evaluated."} {"id": "PMID:173749", "title": "Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case.", "content": "Previous discussions center on early diagnosis, initial treatment, and follow-up therapy for the patient with vitamin D-resistant rickets. Both the medical and dental aspects of treatment for these patients has a long-range effect on the normal developmental patterns. Although treatment is begun at an early age, some rachitic skeletal effects such as minor bowing of the legs and bossing of the skull will invariably be noticed. In patients with controlled rickets the alveolar processes undergo normal development, with apparent normal dental eruption. The poor development and calcification of the alveolus seen in the untreated patient leads to loss of the lamina dura and periodontal ligament of the teeth. Patients with resistant rickets possess a functional dentition, although not without inherent defects. Various degrees of fracture and attrition of enamel can be seen, and hypoplasia of dentin is nearly a universal result. Defects extending to the dentinoenamel junction have been shown in repeated cases. Cementum, because of its close relationship with dentin calcification, also appears abnormal. Pulp tissue may undergo abberations of physiology in resistant rickets, although further work in this respect is needed. With respect to the possible dental pathoses seen in this disease, the dental history of the patient with resistant rickets discussed in this report showed that several of the deciduous teeth, possibly the mandibular left second premolar and right first molar, and definitely the maxillary right second premolar and canine and the mandibular left canine had all undergone pulpal degeneration of apparently unknown causation. In the maxillary right second premolar and the mandibular left canine, enamel fractures were clinically and radiographically apparent. However, the maxillary right canine originally had an acute abscess with no defects other than normal, minimal wear facets. No causative factor for its necrosis could be found. Overt enamel fractures in the maxillary right second premolar and the mandibular left canine may have led to microexposures of the pulp with subsequent bacterial pulpal contamination. Suppuration present in several of the pulps when first entered during endodontic treatment, as well as chronic fistulas in several areas, support the conclusion that contamination by some means does indeed occur.", "contents": "Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case. Previous discussions center on early diagnosis, initial treatment, and follow-up therapy for the patient with vitamin D-resistant rickets. Both the medical and dental aspects of treatment for these patients has a long-range effect on the normal developmental patterns. Although treatment is begun at an early age, some rachitic skeletal effects such as minor bowing of the legs and bossing of the skull will invariably be noticed. In patients with controlled rickets the alveolar processes undergo normal development, with apparent normal dental eruption. The poor development and calcification of the alveolus seen in the untreated patient leads to loss of the lamina dura and periodontal ligament of the teeth. Patients with resistant rickets possess a functional dentition, although not without inherent defects. Various degrees of fracture and attrition of enamel can be seen, and hypoplasia of dentin is nearly a universal result. Defects extending to the dentinoenamel junction have been shown in repeated cases. Cementum, because of its close relationship with dentin calcification, also appears abnormal. Pulp tissue may undergo abberations of physiology in resistant rickets, although further work in this respect is needed. With respect to the possible dental pathoses seen in this disease, the dental history of the patient with resistant rickets discussed in this report showed that several of the deciduous teeth, possibly the mandibular left second premolar and right first molar, and definitely the maxillary right second premolar and canine and the mandibular left canine had all undergone pulpal degeneration of apparently unknown causation. In the maxillary right second premolar and the mandibular left canine, enamel fractures were clinically and radiographically apparent. However, the maxillary right canine originally had an acute abscess with no defects other than normal, minimal wear facets. No causative factor for its necrosis could be found. Overt enamel fractures in the maxillary right second premolar and the mandibular left canine may have led to microexposures of the pulp with subsequent bacterial pulpal contamination. Suppuration present in several of the pulps when first entered during endodontic treatment, as well as chronic fistulas in several areas, support the conclusion that contamination by some means does indeed occur."} {"id": "PMID:173750", "title": "An action of disodium cromoglycate: inhibition of cyclic 3',5'-AMP phosphodiesterase.", "content": "Disodium cromoglycate (DSCG) prevents allergic asthma by inhibiting the release of chemical mediators of immediate-type allergic reactions. The mechanism of this action is unclear and prompted us to examine the effect of DSCG on cyclic adenosine 3',5'-monophosphate (cAMP), the implicated regulator of IgE-mediated reactions. We used the peripheral blood lymphocyte as a model to mirror the biochemical events occurring in the allergic shock organs. Isolated peripheral blood lymphocytes from perennial allergic asthmatic children receiving only DSCG had significantly (p less than 0.005) lower phosphodiesterase (PDE) activity (mean 1.05 +/- 0.17 SE per 10(6) cells) than normal individuals (2.93 +/- 0.14) and allergic children receiving methylxanthines (4.08 +/- 0.28) or no medications (3.58 +/- 0.2). DSCG (10 mug/ml) significantly lowered PDE activity in normal lymphocytes (p less than 0.005) in a beef heart extract (p less than 0.001), and 100 mug/ml lowered PDE activity in fetal rabbit lung homogenates (p less than 0.001). DSCG (10 mug/ml) significantly elevated (p less than 0.01) cAMP concentration in normal human lymphocytes (118 +/- 38 vs 30 +/- 10 picomoles cAMP/10(6) lymphocytes). Thus, DSCG appears to inhibit chemical mediator release by increasing intracellular cAMP through the inhibition of cAMP PDE.", "contents": "An action of disodium cromoglycate: inhibition of cyclic 3',5'-AMP phosphodiesterase. Disodium cromoglycate (DSCG) prevents allergic asthma by inhibiting the release of chemical mediators of immediate-type allergic reactions. The mechanism of this action is unclear and prompted us to examine the effect of DSCG on cyclic adenosine 3',5'-monophosphate (cAMP), the implicated regulator of IgE-mediated reactions. We used the peripheral blood lymphocyte as a model to mirror the biochemical events occurring in the allergic shock organs. Isolated peripheral blood lymphocytes from perennial allergic asthmatic children receiving only DSCG had significantly (p less than 0.005) lower phosphodiesterase (PDE) activity (mean 1.05 +/- 0.17 SE per 10(6) cells) than normal individuals (2.93 +/- 0.14) and allergic children receiving methylxanthines (4.08 +/- 0.28) or no medications (3.58 +/- 0.2). DSCG (10 mug/ml) significantly lowered PDE activity in normal lymphocytes (p less than 0.005) in a beef heart extract (p less than 0.001), and 100 mug/ml lowered PDE activity in fetal rabbit lung homogenates (p less than 0.001). DSCG (10 mug/ml) significantly elevated (p less than 0.01) cAMP concentration in normal human lymphocytes (118 +/- 38 vs 30 +/- 10 picomoles cAMP/10(6) lymphocytes). Thus, DSCG appears to inhibit chemical mediator release by increasing intracellular cAMP through the inhibition of cAMP PDE."} {"id": "PMID:173754", "title": "The behaviour of porcine cytomegalovirus in commercial pig herds.", "content": "A longitudinal, virological and serological study of pigs in two herds with respiratory disease showed that infection by porcine cytomegalovirus (PCMV) was universal in both. Virus excretion usually began when piglets were between 3 and 6 weeks of age and reached a maximum between 5 and 8 weeks; it was usually no longer detectable at 11-12 weeks. Antibody demonstrable in indirect immunofluorescence (IIF) tests was present to moderate or high titre in all piglets at 2-3 weeks. This was presumed to be maternal in origin as it declined in titre between 2-3 and 5-6 weeks. After this fall the majority of piglets showed seroconversion as a result of virus infection. One group of 12 pigs in which infection occurred earlier than usual showed a very poor antibody response, which, nevertheless, persisted through to week 27. The findings are discussed with relation to porcine atrophic rhinitis and cytomegalovirus infection in other species.", "contents": "The behaviour of porcine cytomegalovirus in commercial pig herds. A longitudinal, virological and serological study of pigs in two herds with respiratory disease showed that infection by porcine cytomegalovirus (PCMV) was universal in both. Virus excretion usually began when piglets were between 3 and 6 weeks of age and reached a maximum between 5 and 8 weeks; it was usually no longer detectable at 11-12 weeks. Antibody demonstrable in indirect immunofluorescence (IIF) tests was present to moderate or high titre in all piglets at 2-3 weeks. This was presumed to be maternal in origin as it declined in titre between 2-3 and 5-6 weeks. After this fall the majority of piglets showed seroconversion as a result of virus infection. One group of 12 pigs in which infection occurred earlier than usual showed a very poor antibody response, which, nevertheless, persisted through to week 27. The findings are discussed with relation to porcine atrophic rhinitis and cytomegalovirus infection in other species."} {"id": "PMID:173755", "title": "Rhinoviruses in Britain 1963-1973.", "content": "The serological examination of over 900 rhinovirus strains isolated in Britain over a 10-year period has demonstrated a wide variety of different serotypes. Their seasonal and temporal distribution are described and discussed.", "contents": "Rhinoviruses in Britain 1963-1973. The serological examination of over 900 rhinovirus strains isolated in Britain over a 10-year period has demonstrated a wide variety of different serotypes. Their seasonal and temporal distribution are described and discussed."} {"id": "PMID:173756", "title": "Enhancement of reaginic and hemagglutinating antibody production by an extract of Bordetella pertussis containing histamine sensitizing factor.", "content": "The effect of an extract containing the histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of mice to ovalbumin was investigated with respect to dose of antigen and adjuvant. Of particular interest was the enhancement of reaginic antibody production. In comparison to the Al(OH)3 induced production of reaginic antibody where low doses of antigen and adjuvant yield high titers of reagin, the HSF extract demonstrated optimal adjuvant activity at high doses of both adjuvant and antigen. The reaginic antibody response was maximal usually by 2 to 3 weeks post-immunization and persisted for long periods of time. The hemagglutinating antibody response was maximal at 8 to 10 weeks post-immunization. The initial treatment of mice with HSF extract plus antigen resulted in the production of memory cells since a subsequent immunization with ovalbumin alone evoked a secondary reaginic response. These observations may have implications in clinical allergy since substances similar to the pertussis factor might be produced by other microbial organisms and these substances could modulate the immunologic response of individuals to common allergens.", "contents": "Enhancement of reaginic and hemagglutinating antibody production by an extract of Bordetella pertussis containing histamine sensitizing factor. The effect of an extract containing the histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of mice to ovalbumin was investigated with respect to dose of antigen and adjuvant. Of particular interest was the enhancement of reaginic antibody production. In comparison to the Al(OH)3 induced production of reaginic antibody where low doses of antigen and adjuvant yield high titers of reagin, the HSF extract demonstrated optimal adjuvant activity at high doses of both adjuvant and antigen. The reaginic antibody response was maximal usually by 2 to 3 weeks post-immunization and persisted for long periods of time. The hemagglutinating antibody response was maximal at 8 to 10 weeks post-immunization. The initial treatment of mice with HSF extract plus antigen resulted in the production of memory cells since a subsequent immunization with ovalbumin alone evoked a secondary reaginic response. These observations may have implications in clinical allergy since substances similar to the pertussis factor might be produced by other microbial organisms and these substances could modulate the immunologic response of individuals to common allergens."} {"id": "PMID:173757", "title": "Antibody-dependent cell-mediated cytotoxicity to target cells infected with type 1 and type 2 herpes simplex virus.", "content": "The phenomenon of antibody-dependent cell-mediated cytoxicity (ADCC) has been extended to include target cells acutely infected with herpes simplex type 1 virus (HSV-1) or herpes simplex type 2 virus (HSV-2) in an in vitro system that employs immune human serum and human blood mononuclear cells. The cytotoxic reaction was detectable after 1 hr of incubation and was complete between 4 and 8 hr. The amount of ADCC noted was directly proportional to the logarithm(10) of the effector: target cell ratio (E:T), and ADCC was noted at E:T as low as 1:1. The mononuclear effector cell was present in the blood of both HSV immune and non-immune individuals. The immune serum factor was demonstrated to be an antibody with specificity for HSV membrane antigen(s) and was reactive with target cells infected with either of the two HSV types. The antibody rendered the mononuclear cell cytotoxic by sensitization of the target cell rather than by direct attachment to or \"arming\" of the mononuclear cell. The physiochemical properties of the antibody as well as its presence in cord blood demonstrated that it is an immunoglobulin on the IgG class.", "contents": "Antibody-dependent cell-mediated cytotoxicity to target cells infected with type 1 and type 2 herpes simplex virus. The phenomenon of antibody-dependent cell-mediated cytoxicity (ADCC) has been extended to include target cells acutely infected with herpes simplex type 1 virus (HSV-1) or herpes simplex type 2 virus (HSV-2) in an in vitro system that employs immune human serum and human blood mononuclear cells. The cytotoxic reaction was detectable after 1 hr of incubation and was complete between 4 and 8 hr. The amount of ADCC noted was directly proportional to the logarithm(10) of the effector: target cell ratio (E:T), and ADCC was noted at E:T as low as 1:1. The mononuclear effector cell was present in the blood of both HSV immune and non-immune individuals. The immune serum factor was demonstrated to be an antibody with specificity for HSV membrane antigen(s) and was reactive with target cells infected with either of the two HSV types. The antibody rendered the mononuclear cell cytotoxic by sensitization of the target cell rather than by direct attachment to or \"arming\" of the mononuclear cell. The physiochemical properties of the antibody as well as its presence in cord blood demonstrated that it is an immunoglobulin on the IgG class."} {"id": "PMID:173758", "title": "Mechanism of immunologic resistance to herpes simplex virus 1 (HSV-1) infection.", "content": "Susceptibility of adult mice to i.p. infection with HSV-1 was greatly increased by administration of a single dose of cyclophosphamide. Mortality of cyclophosphamide-treated virus-infected mice was associated with increased virus replication and pathologic changes in brain and liver. The development of a fatal infection in immunosuppressed mice could be curtailed after transfer of specifically immune spleen cells. Passively transferred antibody had no such effect. Protective activity of spleen cells was significantly reduced after pretreatment with anti-theta serum. Significant protection was also achieved when normal spleen cells plus immune serum were administered simultaneously. Our results indicate that protection against this virus infection is predominantly T cell dependent, and suggests that antibody-dependent cell-mediated protection may also be operative in vivo.", "contents": "Mechanism of immunologic resistance to herpes simplex virus 1 (HSV-1) infection. Susceptibility of adult mice to i.p. infection with HSV-1 was greatly increased by administration of a single dose of cyclophosphamide. Mortality of cyclophosphamide-treated virus-infected mice was associated with increased virus replication and pathologic changes in brain and liver. The development of a fatal infection in immunosuppressed mice could be curtailed after transfer of specifically immune spleen cells. Passively transferred antibody had no such effect. Protective activity of spleen cells was significantly reduced after pretreatment with anti-theta serum. Significant protection was also achieved when normal spleen cells plus immune serum were administered simultaneously. Our results indicate that protection against this virus infection is predominantly T cell dependent, and suggests that antibody-dependent cell-mediated protection may also be operative in vivo."} {"id": "PMID:173759", "title": "Adenosine 3'-5'-monophosphate-dependent protein kinases of neonatal human skin.", "content": "Three forms of adenosine 3'-5'-cyclic monophosphate-dependent protein kinases have been isolated from neonatal human skin. An analysis of their properties indicates that they resemble those of cyclic AMP-dependent protein phosphotransferases of adult skin.", "contents": "Adenosine 3'-5'-monophosphate-dependent protein kinases of neonatal human skin. Three forms of adenosine 3'-5'-cyclic monophosphate-dependent protein kinases have been isolated from neonatal human skin. An analysis of their properties indicates that they resemble those of cyclic AMP-dependent protein phosphotransferases of adult skin."} {"id": "PMID:173760", "title": "Diarrhea caused in gnotobiotic piglets by the reovirus-like agent of human infantile gastroenteritis.", "content": "One- to four-day-old gnotobiotic piglets were inoculated orally with a reovirus-like agent obtained from human infants with acute gastroenteritis. Diarrhea developed in the piglets two to seven days after inoculation and was reproduced for five serial passages in one sequence and for three passages in another. Nineteen of 21 inoculated piglets developed diarrhea; reovirus-like particles were observed in intestinal contents and/or fecal samples from 17 animals with illness and from two inoculated piglets that did not develop diarrhea. One piglet, for which daily fecal samples were examined by electron microscopy, shed the largest number of virus particles at the onset of diarrhea. Immunofluorescent antibody responses to the reovirus-like agent were detected in sera from the seven inoculated animals that were tested.", "contents": "Diarrhea caused in gnotobiotic piglets by the reovirus-like agent of human infantile gastroenteritis. One- to four-day-old gnotobiotic piglets were inoculated orally with a reovirus-like agent obtained from human infants with acute gastroenteritis. Diarrhea developed in the piglets two to seven days after inoculation and was reproduced for five serial passages in one sequence and for three passages in another. Nineteen of 21 inoculated piglets developed diarrhea; reovirus-like particles were observed in intestinal contents and/or fecal samples from 17 animals with illness and from two inoculated piglets that did not develop diarrhea. One piglet, for which daily fecal samples were examined by electron microscopy, shed the largest number of virus particles at the onset of diarrhea. Immunofluorescent antibody responses to the reovirus-like agent were detected in sera from the seven inoculated animals that were tested."} {"id": "PMID:173761", "title": "Transmission of experimental rhinovirus colds in volunteer married couples.", "content": "Communicability of rhinovirus type 16 or type 55 was studied in 24 childless couples; on partner (the donor) was infected with laboratory-grown virus. Initially, both partners lacked antibody to the challenge agent. Rates of transmission between partners were 41% and 33% for type 16 and type 55, respectively. These rates are similar to those determined in epidemiologic studies of natural rhinovirus infection. Although the mucosa of the anterior nares was shown to be highly susceptible to infection (less than one 50% tissue culture infective dose [TCID50]), transmission rarely occurred unless (1) at least 1,000 TCID50 of virus was recovered from the donor's nasal washing, (2) the donor had virus on his hands and anterior nares, (3) he was at least moderately symptomatic, and (4) he spent many hours with his spouse. Since person-to-person transfer of rhinovirus was so dependent upon time spent together and shedding of large amounts of virus by the donor, it seems possible that the chain of infection could be interrupted by environmental manipulation.", "contents": "Transmission of experimental rhinovirus colds in volunteer married couples. Communicability of rhinovirus type 16 or type 55 was studied in 24 childless couples; on partner (the donor) was infected with laboratory-grown virus. Initially, both partners lacked antibody to the challenge agent. Rates of transmission between partners were 41% and 33% for type 16 and type 55, respectively. These rates are similar to those determined in epidemiologic studies of natural rhinovirus infection. Although the mucosa of the anterior nares was shown to be highly susceptible to infection (less than one 50% tissue culture infective dose [TCID50]), transmission rarely occurred unless (1) at least 1,000 TCID50 of virus was recovered from the donor's nasal washing, (2) the donor had virus on his hands and anterior nares, (3) he was at least moderately symptomatic, and (4) he spent many hours with his spouse. Since person-to-person transfer of rhinovirus was so dependent upon time spent together and shedding of large amounts of virus by the donor, it seems possible that the chain of infection could be interrupted by environmental manipulation."} {"id": "PMID:173762", "title": "A rhesus monkey model for the study of Bolivian hemorrhagic fever.", "content": "Two groups of rhesus monkeys were inoculated with either 10(5) (group 1) or 10(3) (group 2) plaque-forming units of Machupo virus, the etiologic virus of Bolivian hemorrhagic fever. The monkeys were observed for clinical signs; body temperatures, viremias, hematologic changes, and virus-neutralizing antibody were measured. The onset of clinical signs for groups 1 and 2 occurred on days 4-6 and 7-10, respectively, with fever, anorexia, and depression. These and other signs became more severe, and all of the monkeys died; the respective mean times to death for groups 1 and 2 were 14.3 and 19.5 days. Hematocrit, neutrophil, and lymphocyte values decreased in both groups until a few days before death and then increased slightly. Viremias in the two groups peaked on days 13 and 16, respectively, and persisted until death; the sole exception was one monkey in group 2 that developed neutralizing antibody by day 21. The response of the rhesus monkey to Machupo virus thus provides a useful model for the study of Bolivian hemorrhagic fever.", "contents": "A rhesus monkey model for the study of Bolivian hemorrhagic fever. Two groups of rhesus monkeys were inoculated with either 10(5) (group 1) or 10(3) (group 2) plaque-forming units of Machupo virus, the etiologic virus of Bolivian hemorrhagic fever. The monkeys were observed for clinical signs; body temperatures, viremias, hematologic changes, and virus-neutralizing antibody were measured. The onset of clinical signs for groups 1 and 2 occurred on days 4-6 and 7-10, respectively, with fever, anorexia, and depression. These and other signs became more severe, and all of the monkeys died; the respective mean times to death for groups 1 and 2 were 14.3 and 19.5 days. Hematocrit, neutrophil, and lymphocyte values decreased in both groups until a few days before death and then increased slightly. Viremias in the two groups peaked on days 13 and 16, respectively, and persisted until death; the sole exception was one monkey in group 2 that developed neutralizing antibody by day 21. The response of the rhesus monkey to Machupo virus thus provides a useful model for the study of Bolivian hemorrhagic fever."} {"id": "PMID:173763", "title": "Synergistic antiviral effects of adenine arabinoside and humoral antibodies in experimental encephalitis due to Herpesvirus hominis.", "content": "The antiviral effects of humoral antibodies and adenine arabinoside on encephalitis due to Herpesvirus hominis were studied in three-week-old mice. Exogenously administered antibodies to H. hominis, of rabbit or human origin, significantly reduced morbidity and mortality rates from H. hominis encephalitis if enough antibodies were given during the early phase of infection. Adenine arabinoside could also modulate the pathogenesis and reduce the mortality rate in mice with H. hominis encephalitis. Simultaneous administration of adenine arabinoside and human immune globulin resulted in an enhanced protection against H. hominis encephalitis. This increased protection was manifested by a significant reduction of mortality rate, a decrease in concentration of virus, and a lessening of histopathologic damage in the brain tissues. Mechanisms involved in the enhanced protective effects were not well defined. The use of adenine arabinoside plus human immune globulin did not completely suppress viral replication. Therefore, host recovery was probably mediated through (1) partial suppression of viral replication by adenine arabinoside, (2) neutralization of cell-free virus by antibodies, and (3) collaboration of antibodies with other host resistance factors (e.g., complement, leukocytes, nonimmune effector cells, etc.). Our data suggest that control of severe H. hominis infection may require the combined use of an antiviral agent and humoral factor and, perhaps, enhancement of host responses by other means.", "contents": "Synergistic antiviral effects of adenine arabinoside and humoral antibodies in experimental encephalitis due to Herpesvirus hominis. The antiviral effects of humoral antibodies and adenine arabinoside on encephalitis due to Herpesvirus hominis were studied in three-week-old mice. Exogenously administered antibodies to H. hominis, of rabbit or human origin, significantly reduced morbidity and mortality rates from H. hominis encephalitis if enough antibodies were given during the early phase of infection. Adenine arabinoside could also modulate the pathogenesis and reduce the mortality rate in mice with H. hominis encephalitis. Simultaneous administration of adenine arabinoside and human immune globulin resulted in an enhanced protection against H. hominis encephalitis. This increased protection was manifested by a significant reduction of mortality rate, a decrease in concentration of virus, and a lessening of histopathologic damage in the brain tissues. Mechanisms involved in the enhanced protective effects were not well defined. The use of adenine arabinoside plus human immune globulin did not completely suppress viral replication. Therefore, host recovery was probably mediated through (1) partial suppression of viral replication by adenine arabinoside, (2) neutralization of cell-free virus by antibodies, and (3) collaboration of antibodies with other host resistance factors (e.g., complement, leukocytes, nonimmune effector cells, etc.). Our data suggest that control of severe H. hominis infection may require the combined use of an antiviral agent and humoral factor and, perhaps, enhancement of host responses by other means."} {"id": "PMID:173764", "title": "Clinical efficacy of adenine arabinoside in therapy of cytomegalovirus infections in renal allograft recipients.", "content": "Three renal allograft recipients, two with cytomegalovirus pneumonia and one with cytomegalovirus retinitis, were treated with adenine arabinoside. The dose was 5-10 mg/kg per day administered for four to six days. There was no clinical improvement in any of the patients. One patient died from overwhelming interstitial viral pneumonia. Cytomegalovirus was readily isolated from two patients after therapy (autopsied lung of one and the saliva of the other). Suppression of viruria was observed and quantitated in one patient (10(4.0)-10(2.5) 50% tissue culture infective doses/0.2 ml). However, the suppression was transient, and viral titers returned to the levels before therapy within two months after completion of therapy. Treatment was stopped in two cases when hematologic toxicity (drop in hematocrit and platelet and leukocyte counts) was noted in the patients five days after initiation of therapy with adenine arabinoside. The drug appears to be ineffective and possibly toxic in immunosuppressed renal allograft recipients infected with cytomegalovirus.", "contents": "Clinical efficacy of adenine arabinoside in therapy of cytomegalovirus infections in renal allograft recipients. Three renal allograft recipients, two with cytomegalovirus pneumonia and one with cytomegalovirus retinitis, were treated with adenine arabinoside. The dose was 5-10 mg/kg per day administered for four to six days. There was no clinical improvement in any of the patients. One patient died from overwhelming interstitial viral pneumonia. Cytomegalovirus was readily isolated from two patients after therapy (autopsied lung of one and the saliva of the other). Suppression of viruria was observed and quantitated in one patient (10(4.0)-10(2.5) 50% tissue culture infective doses/0.2 ml). However, the suppression was transient, and viral titers returned to the levels before therapy within two months after completion of therapy. Treatment was stopped in two cases when hematologic toxicity (drop in hematocrit and platelet and leukocyte counts) was noted in the patients five days after initiation of therapy with adenine arabinoside. The drug appears to be ineffective and possibly toxic in immunosuppressed renal allograft recipients infected with cytomegalovirus."} {"id": "PMID:173765", "title": "An improved method for the extraction of endogenous platelet serotonin.", "content": "Investigations of blood platelet serotonin content, turnover, metabolism, and secretion require sensitive methods for accurate measurement of the amine. The present study has sought a simple, efficient procedure for extracting total platelet serotonin which could also be used for analysis of other platelet chemical constituents. ZnSO4 precipitation, the standard technique for extracting 5-HT, failed to recover total platelet serotonin despite physical and chemical manipulations to improve its availability. Perchloric acid extraction was found to be more efficient, resulting in significantly increased values for endogenous platelet serotonin and recovery of 97 per cent of standard amounts of 5-HT added to platelet pellets. In addition, the perchloric acid extracts could be used for analysis of other platelet constituents such as adenine nucleotides. The improved procedure eliminates the need for large numbers of replicate samples for several assays and, at the same time, provides a more sensitive method for recovery of total platelet serotonin. It may also prove valuable for prolonged in vitro experiments in which extraction must be followed by additional isolation procedures in order to separate indole metabolites of serotonin from the amine for specific quantitation.", "contents": "An improved method for the extraction of endogenous platelet serotonin. Investigations of blood platelet serotonin content, turnover, metabolism, and secretion require sensitive methods for accurate measurement of the amine. The present study has sought a simple, efficient procedure for extracting total platelet serotonin which could also be used for analysis of other platelet chemical constituents. ZnSO4 precipitation, the standard technique for extracting 5-HT, failed to recover total platelet serotonin despite physical and chemical manipulations to improve its availability. Perchloric acid extraction was found to be more efficient, resulting in significantly increased values for endogenous platelet serotonin and recovery of 97 per cent of standard amounts of 5-HT added to platelet pellets. In addition, the perchloric acid extracts could be used for analysis of other platelet constituents such as adenine nucleotides. The improved procedure eliminates the need for large numbers of replicate samples for several assays and, at the same time, provides a more sensitive method for recovery of total platelet serotonin. It may also prove valuable for prolonged in vitro experiments in which extraction must be followed by additional isolation procedures in order to separate indole metabolites of serotonin from the amine for specific quantitation."} {"id": "PMID:173766", "title": "Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man.", "content": "Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal.", "contents": "Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man. Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal."} {"id": "PMID:173767", "title": "Recent advances in our understanding of the vitamin D endocrine system.", "content": "Vitamin D3 gives rise to at least one hormone in which the kidney is utilized as an endocrine system. This hormone arises from 25-OH-D3 which in turn is synthesized in the liver from vitamin D3. The production of this calcium and phosphorus mobilizing hormone, namely 1,25-(OH)2D3, is strongly regulated by the need for calcium and phosphorus. The regulation of its production can occur only after initial 1,25-(OH)2D3 is made and brings about the appearance of 25-OH-D3-24hydroxylase. The need for calcium brings about a stimulation of parathyroid hormone secretion. The parathyroid hormone suppresses the 24-hydroxylase and stimulates the 1-hydroxylase. Alternatively, the need for phosphorus directly stimulates the 1-hydroxylase and suppresses the 24-hydroxylase. The 24-hydroxylation appears to be the initial reaction leading to the inactivation and excretion of vitamin D whereas the 1-hydroxylation is the reaction bringing about the activation of the molecule to 1,25-(OH)2D3. The 1,25-(OH)2D3, the 25-OH-D3 and an analog of 1,25-(OH)2D3, namely 1alpha-OH-D3, are potentially extremely useful in the treatment of metabolic bone diseases such as renal osteodystrophy, hepatically related disorders of calcium and bone metabolism, hypoparathyroidism, and vitamin D dependency disease. The 1alpha-OH-D3 is effective by virtue of its conversion to 1,25-(OH)2D3. The 25-hydroxylation of both 1alpha-OH-D3 and vitamin D3 itself occurs predominantly in the liver. Finally, it is not entirely settled whether 1,25-(OH)2D3 is active directly in all of the functions of viramin D or whether it must be further converted metabolically. A new metabolic pathway for vitamin D has been discovered in which 1,25-(OH)2D3 loses its 26 and 27 carbons to carbon dioxide, producing an unknown metabolite. It is not certain whether this pathway represents degradation of the 1,25-(OH)2D3 or its further activation.", "contents": "Recent advances in our understanding of the vitamin D endocrine system. Vitamin D3 gives rise to at least one hormone in which the kidney is utilized as an endocrine system. This hormone arises from 25-OH-D3 which in turn is synthesized in the liver from vitamin D3. The production of this calcium and phosphorus mobilizing hormone, namely 1,25-(OH)2D3, is strongly regulated by the need for calcium and phosphorus. The regulation of its production can occur only after initial 1,25-(OH)2D3 is made and brings about the appearance of 25-OH-D3-24hydroxylase. The need for calcium brings about a stimulation of parathyroid hormone secretion. The parathyroid hormone suppresses the 24-hydroxylase and stimulates the 1-hydroxylase. Alternatively, the need for phosphorus directly stimulates the 1-hydroxylase and suppresses the 24-hydroxylase. The 24-hydroxylation appears to be the initial reaction leading to the inactivation and excretion of vitamin D whereas the 1-hydroxylation is the reaction bringing about the activation of the molecule to 1,25-(OH)2D3. The 1,25-(OH)2D3, the 25-OH-D3 and an analog of 1,25-(OH)2D3, namely 1alpha-OH-D3, are potentially extremely useful in the treatment of metabolic bone diseases such as renal osteodystrophy, hepatically related disorders of calcium and bone metabolism, hypoparathyroidism, and vitamin D dependency disease. The 1alpha-OH-D3 is effective by virtue of its conversion to 1,25-(OH)2D3. The 25-hydroxylation of both 1alpha-OH-D3 and vitamin D3 itself occurs predominantly in the liver. Finally, it is not entirely settled whether 1,25-(OH)2D3 is active directly in all of the functions of viramin D or whether it must be further converted metabolically. A new metabolic pathway for vitamin D has been discovered in which 1,25-(OH)2D3 loses its 26 and 27 carbons to carbon dioxide, producing an unknown metabolite. It is not certain whether this pathway represents degradation of the 1,25-(OH)2D3 or its further activation."} {"id": "PMID:173768", "title": "Activation of renal erythropoietic factor by phosphorylation.", "content": "Renal erythropoietic factor (REF) serves as a substrate for a cyclic nucleotide-dependent protein kinase. The phosphorylation of REF is associated with increased erythropoietic activity. Conversely, REF isolated from hypoxic rats is a poor phosphate acceptor. These findings and the presence of a positive correlation between erythropoietin levels and urinary excretion of adenosine 3',5' monophosphate (cyclic-AMP) in anemic individuals suggest that the cyclic-AMP-protein kinase system plays an important role in the activation of REF.", "contents": "Activation of renal erythropoietic factor by phosphorylation. Renal erythropoietic factor (REF) serves as a substrate for a cyclic nucleotide-dependent protein kinase. The phosphorylation of REF is associated with increased erythropoietic activity. Conversely, REF isolated from hypoxic rats is a poor phosphate acceptor. These findings and the presence of a positive correlation between erythropoietin levels and urinary excretion of adenosine 3',5' monophosphate (cyclic-AMP) in anemic individuals suggest that the cyclic-AMP-protein kinase system plays an important role in the activation of REF."} {"id": "PMID:173773", "title": "Effect of acute inhibition of adrenocorticotrophin secretion on plasma corticosteroids in the rhesus monkey (Macaca mulatta).", "content": "The half-life of plasma cortisol in the rhesus monkey (M. mulatta), determined by two methods, was about 130 min and longer than that in man; it was unaffected by administration of dexamethasone. Dexamethasone (5 mg, i.v.) immediately inhibited the secretion of ACTH from the monkey pituitary. The plasma half-life of NH2-terminal immunoreactive ACTH was found to be about 55 min which was much longer than the biological half-life. The adrenal synthesis of cortisol was inhibited by metyrapone which caused a prompt increase in the plasma concentration of ACTH and 11-deoxycortisol. The hypothalamic-pituitary-adrenal system of the rhesus monkey sedated with phencyclidine hydrochloride responded rapidly to alteration in the level of steroids in the circulation.", "contents": "Effect of acute inhibition of adrenocorticotrophin secretion on plasma corticosteroids in the rhesus monkey (Macaca mulatta). The half-life of plasma cortisol in the rhesus monkey (M. mulatta), determined by two methods, was about 130 min and longer than that in man; it was unaffected by administration of dexamethasone. Dexamethasone (5 mg, i.v.) immediately inhibited the secretion of ACTH from the monkey pituitary. The plasma half-life of NH2-terminal immunoreactive ACTH was found to be about 55 min which was much longer than the biological half-life. The adrenal synthesis of cortisol was inhibited by metyrapone which caused a prompt increase in the plasma concentration of ACTH and 11-deoxycortisol. The hypothalamic-pituitary-adrenal system of the rhesus monkey sedated with phencyclidine hydrochloride responded rapidly to alteration in the level of steroids in the circulation."} {"id": "PMID:173784", "title": "Development of a radioimmunoassay for alpha-melanocyte-stimulating hormone in the rat.", "content": "A sensitive and specific radioimmunoassay for alpha-melanocyte-stimulating hormone (alpha-MSH) was developed. Extracts of the neurointermediate lobe of the rat produced displacement curves which were parallel to those obtained with synthetic alpha-MSH. The mean immunoreactive alpha-MSH concentration in neurointermediate lobes from normal adult rats was 2768 +/- 200 (S.E.M.) ng/lobe. This accounted for approximately 78% of the MSH activity of the neurointermediate lobe as measured by bioassay. Much lower levels of immunoreactive alpha-MSH were found in the anterior lobe of the rat. Extracts of rat serum and plasma also contained immunoreactive alpha-MSH and the mean level was found to be 237 +/- 20 pg/ml. This was slightly lower than the level measured in rat plasma by bioassay. Increased levels of alpha-MSH were found in plasma of rats 1 and 3 h after a single injection of trifluoperazine and after 1-5 min of ether anaesthesia. These changes were reflected by decreases in the alpha-MSH content of the neurointermediate lobe.", "contents": "Development of a radioimmunoassay for alpha-melanocyte-stimulating hormone in the rat. A sensitive and specific radioimmunoassay for alpha-melanocyte-stimulating hormone (alpha-MSH) was developed. Extracts of the neurointermediate lobe of the rat produced displacement curves which were parallel to those obtained with synthetic alpha-MSH. The mean immunoreactive alpha-MSH concentration in neurointermediate lobes from normal adult rats was 2768 +/- 200 (S.E.M.) ng/lobe. This accounted for approximately 78% of the MSH activity of the neurointermediate lobe as measured by bioassay. Much lower levels of immunoreactive alpha-MSH were found in the anterior lobe of the rat. Extracts of rat serum and plasma also contained immunoreactive alpha-MSH and the mean level was found to be 237 +/- 20 pg/ml. This was slightly lower than the level measured in rat plasma by bioassay. Increased levels of alpha-MSH were found in plasma of rats 1 and 3 h after a single injection of trifluoperazine and after 1-5 min of ether anaesthesia. These changes were reflected by decreases in the alpha-MSH content of the neurointermediate lobe."} {"id": "PMID:173785", "title": "Interrelationships of pituitary and plasma corticotrophin and plasma corticosterone during adrenocortical regeneration in the rat.", "content": "Pituitary and plasma ACTH and plasma corticosterone were measured at various times after adrenal enucleation or adrenalectomy. The changes in ACTH could be inversely correlated with those in plasma corticosterone. They could also be prevented by maintenance therapy with the steroid. The results indicate that the corticosteroids control both the release and the synthesis of ACTH but that their effect is predominantly on the release of the hormone.", "contents": "Interrelationships of pituitary and plasma corticotrophin and plasma corticosterone during adrenocortical regeneration in the rat. Pituitary and plasma ACTH and plasma corticosterone were measured at various times after adrenal enucleation or adrenalectomy. The changes in ACTH could be inversely correlated with those in plasma corticosterone. They could also be prevented by maintenance therapy with the steroid. The results indicate that the corticosteroids control both the release and the synthesis of ACTH but that their effect is predominantly on the release of the hormone."} {"id": "PMID:173786", "title": "Cytoplasmic oestrogen receptor complex of female ovine pituitary: changes associated with the reproductive state and oestradiol treatment.", "content": "Binding of oestrone and oestradiol to a pituitary cytosol receptor was studied in ovariectomized sheep during the breeding season, during anoestrus and after oestradiol treatment during anoestrus. All sheep were ovariectomized 2 weeks before removal of the anterior pituitary. Oestrogen treatment consisted of the subcutaneous implantation of Silastic capsules containing oestradiol-17beta 3 weeks before ovariectomy. Association constants (KA) for oestrone and oestradiol and the concentration of binding sites for oestradiol varied with changes in reproductive state. Oestradiol bound more tightly and the concentration of available binding sites was lower during the breeding season than during anoestrus. The affinity of oestrone binding was less during the breeding season than during anoestrus, whilst the concentration of binding sites for this steroid did not change with changes in reproductive state. Treatment of anoestrous sheeep with oestradiol increased the KA for oestradiol and decreased the concentration of binding sites. However, no effect of oestradiol treatment was observed with regard to the KA or concentration of binding sites for oestrone. The results suggest that either the pituitary oestrogen cytoplasmic receptor undergoes a conformational change during the breeding season causing oestradiol to be more tightly bound or the onset of the breeding season is accompanied by the appearance of a new receptor which binds to oestradiol with greater affinity. Oestradiol treatment of anoestrous sheep mimics this change.", "contents": "Cytoplasmic oestrogen receptor complex of female ovine pituitary: changes associated with the reproductive state and oestradiol treatment. Binding of oestrone and oestradiol to a pituitary cytosol receptor was studied in ovariectomized sheep during the breeding season, during anoestrus and after oestradiol treatment during anoestrus. All sheep were ovariectomized 2 weeks before removal of the anterior pituitary. Oestrogen treatment consisted of the subcutaneous implantation of Silastic capsules containing oestradiol-17beta 3 weeks before ovariectomy. Association constants (KA) for oestrone and oestradiol and the concentration of binding sites for oestradiol varied with changes in reproductive state. Oestradiol bound more tightly and the concentration of available binding sites was lower during the breeding season than during anoestrus. The affinity of oestrone binding was less during the breeding season than during anoestrus, whilst the concentration of binding sites for this steroid did not change with changes in reproductive state. Treatment of anoestrous sheeep with oestradiol increased the KA for oestradiol and decreased the concentration of binding sites. However, no effect of oestradiol treatment was observed with regard to the KA or concentration of binding sites for oestrone. The results suggest that either the pituitary oestrogen cytoplasmic receptor undergoes a conformational change during the breeding season causing oestradiol to be more tightly bound or the onset of the breeding season is accompanied by the appearance of a new receptor which binds to oestradiol with greater affinity. Oestradiol treatment of anoestrous sheep mimics this change."} {"id": "PMID:173787", "title": "Motor patterns in the stomatogastric ganglion of the lobster Panulirus argus.", "content": "1. Acitivity patterns arising from the thirty cells of the stomatogastric ganglion of Panulirus argus are described for both a semi-intact preparation and an isolated one. 2. The thirty or so cells can be divided so far into two functional groupings: the gastric mill group, with at least ten motor elements, and the pyloric group with at least fourteen. There is some, but not extensive, interaction between groups. 3. The main gastric mill activity is arranged in two sets of elements, each of which is composed of reciprocating elements innervating antagonistic muscles. Thus alternation in activity between the single LC and the two LG neurones results in alternate closing and opening of the lateral teeth; alternation between the four GM and single CP units results in alternate protraction and retraction of the medial tooth. 4. The two sets are phased to each other in such a way that they cause gastric mill teeth to operate effectively to masticate food. 5. The main pyloric activity is arranged in a three-part cycle with each of three sets of units active in sequence. Activity in two PD and one AB unit is followed by bursts in IC and LP units followed in turn by activity in up to seven PY units. Activity in a single VD neurone is locked to this cycle in a more complex pattern.", "contents": "Motor patterns in the stomatogastric ganglion of the lobster Panulirus argus. 1. Acitivity patterns arising from the thirty cells of the stomatogastric ganglion of Panulirus argus are described for both a semi-intact preparation and an isolated one. 2. The thirty or so cells can be divided so far into two functional groupings: the gastric mill group, with at least ten motor elements, and the pyloric group with at least fourteen. There is some, but not extensive, interaction between groups. 3. The main gastric mill activity is arranged in two sets of elements, each of which is composed of reciprocating elements innervating antagonistic muscles. Thus alternation in activity between the single LC and the two LG neurones results in alternate closing and opening of the lateral teeth; alternation between the four GM and single CP units results in alternate protraction and retraction of the medial tooth. 4. The two sets are phased to each other in such a way that they cause gastric mill teeth to operate effectively to masticate food. 5. The main pyloric activity is arranged in a three-part cycle with each of three sets of units active in sequence. Activity in two PD and one AB unit is followed by bursts in IC and LP units followed in turn by activity in up to seven PY units. Activity in a single VD neurone is locked to this cycle in a more complex pattern."} {"id": "PMID:173790", "title": "Kinetics of 3-O-methyl glucose transport in red blood cells of newborn pigs.", "content": "The glucose-permeable fetal red cells in the pig are entirely replaced by glucose-impermeable adult red cells within a month after birth. This study investigates the kinetic parameters of the glucose transport mechanism in newborn pig red cells in comparison with immature adult red cells (reticulocytes) as well as the fully matured adult erythrocytes. Influx and efflux of the nonmetabolizable 3-O-methyl glucose (3-O-M-G) in red cells of newborn pigs saturate at high substrate concentrations and exhibit typical Michaelis-Menten kinetics. Km values for efflux are 15.2 and 18.2 mM for 15 and 22 degrees C, respectively. Q10 computed between 10 and 26 degrees is 5.0. The energy of activation for the transport process is 34,000 cal mol-1. The effectiveness of hexoses in competing with 3-O-M-G in efflux is in the following order: D-glucose greater than D-mannose greater than D-fructose greater than D-galactose. Efflux of 3-O-M-G does not increase with 3-O-M-G or D-ribose in the medium and is reduced by 2,4-dinitroflurobenzene (DNFB), p-chloromercuriphenyl sufonic acid (PCMBS), and phloridzin. The reticulocytes are shown to possess a carrier-mediated transport but with a considerably lower transport rate. As the reticulocytes mature into normal red cells, the carrier transport mechanism is lost.", "contents": "Kinetics of 3-O-methyl glucose transport in red blood cells of newborn pigs. The glucose-permeable fetal red cells in the pig are entirely replaced by glucose-impermeable adult red cells within a month after birth. This study investigates the kinetic parameters of the glucose transport mechanism in newborn pig red cells in comparison with immature adult red cells (reticulocytes) as well as the fully matured adult erythrocytes. Influx and efflux of the nonmetabolizable 3-O-methyl glucose (3-O-M-G) in red cells of newborn pigs saturate at high substrate concentrations and exhibit typical Michaelis-Menten kinetics. Km values for efflux are 15.2 and 18.2 mM for 15 and 22 degrees C, respectively. Q10 computed between 10 and 26 degrees is 5.0. The energy of activation for the transport process is 34,000 cal mol-1. The effectiveness of hexoses in competing with 3-O-M-G in efflux is in the following order: D-glucose greater than D-mannose greater than D-fructose greater than D-galactose. Efflux of 3-O-M-G does not increase with 3-O-M-G or D-ribose in the medium and is reduced by 2,4-dinitroflurobenzene (DNFB), p-chloromercuriphenyl sufonic acid (PCMBS), and phloridzin. The reticulocytes are shown to possess a carrier-mediated transport but with a considerably lower transport rate. As the reticulocytes mature into normal red cells, the carrier transport mechanism is lost."} {"id": "PMID:173791", "title": "Enzyme activity changes during cyclic AMP-induced stalk cell differentiation in P4, a variant of Dictyostelium discoideum.", "content": "The P4 variant of Dictyostelium discoideum is characterized by the production of fruiting structures in which the overall proportion of stalk to spore material is increased, relative to the wild type. The altered morphology of the mutant is due to increased sensitivity to cyclic AMP which promotes stalk cell differentiation. In the presence of 10-4 M-cyclic AMP the entire population of P4 amoebae forms clumps of stalk cells on the surface of the dialysis membrane support. Measurement of changes in activity of a range of developmentally-regulated enzymes during the development of P4 in the presence and absence of cyclic AMP has allowed us to identify three classes of enzyme: (i) Those, such as beta-glucosidase II, trehalose-6-phosphate synthetase and uridine diphosphogalactose-4-epimerase, which are required for the production of spores. (ii) Enzymes, primarily but perhaps not exclusively, required during stalk cell formation. Typical of these are N-acetylglucosaminidase and alkaline phosphatase. (iii) General enzymes, such as threonine dehydrase, alpha-mannosidase and uridine diphosphoglucose pyrophyosphorylase, which are present inboth pre-stalk and pre-spore cells and appear to be necessary for the development of both cell types.", "contents": "Enzyme activity changes during cyclic AMP-induced stalk cell differentiation in P4, a variant of Dictyostelium discoideum. The P4 variant of Dictyostelium discoideum is characterized by the production of fruiting structures in which the overall proportion of stalk to spore material is increased, relative to the wild type. The altered morphology of the mutant is due to increased sensitivity to cyclic AMP which promotes stalk cell differentiation. In the presence of 10-4 M-cyclic AMP the entire population of P4 amoebae forms clumps of stalk cells on the surface of the dialysis membrane support. Measurement of changes in activity of a range of developmentally-regulated enzymes during the development of P4 in the presence and absence of cyclic AMP has allowed us to identify three classes of enzyme: (i) Those, such as beta-glucosidase II, trehalose-6-phosphate synthetase and uridine diphosphogalactose-4-epimerase, which are required for the production of spores. (ii) Enzymes, primarily but perhaps not exclusively, required during stalk cell formation. Typical of these are N-acetylglucosaminidase and alkaline phosphatase. (iii) General enzymes, such as threonine dehydrase, alpha-mannosidase and uridine diphosphoglucose pyrophyosphorylase, which are present inboth pre-stalk and pre-spore cells and appear to be necessary for the development of both cell types."} {"id": "PMID:173793", "title": "Mutations in Escherichia coli that relieve catabolite repression of tryptophanase synthesis. Mutations distant from the tryptophanase gene.", "content": "Two mutants are described in which the synthesis of tryptophanase is unusually insensitive to catabolite repression. Neither mutation is linked by transduction to the tryptophane structural gene, neither mutation renders the synthesis of beta-galactosidase insensitive to catabolite repression, and the mutations do not permit tryptophanase to be synthesized in strains deficient in adenyl cyclase. During growth in glucose-minimal medium the mutants maintained a similar intracellular concentration of cyclic AMP to their wild-type parent; but since in the wild type the concentration of cyclic AMP was the same in glycerol-minimal medium as in glucose-minimal medium, it is doubtful whether catabolite repression is mediated by measurable changes in the concentration of this nucleotide.", "contents": "Mutations in Escherichia coli that relieve catabolite repression of tryptophanase synthesis. Mutations distant from the tryptophanase gene. Two mutants are described in which the synthesis of tryptophanase is unusually insensitive to catabolite repression. Neither mutation is linked by transduction to the tryptophane structural gene, neither mutation renders the synthesis of beta-galactosidase insensitive to catabolite repression, and the mutations do not permit tryptophanase to be synthesized in strains deficient in adenyl cyclase. During growth in glucose-minimal medium the mutants maintained a similar intracellular concentration of cyclic AMP to their wild-type parent; but since in the wild type the concentration of cyclic AMP was the same in glycerol-minimal medium as in glucose-minimal medium, it is doubtful whether catabolite repression is mediated by measurable changes in the concentration of this nucleotide."} {"id": "PMID:173794", "title": "Unique virus-related DNA sequences in sheep progressive pneumonia lung.", "content": "Hybridization studies with [3H]-cDNA of progressive pneumonia, maedi and visna viruses demonstrate that lung DNA from sheep afflicted with progressive interstitial pneumonia possesses virus-related sequences not present in normal sheep lung DNA.", "contents": "Unique virus-related DNA sequences in sheep progressive pneumonia lung. Hybridization studies with [3H]-cDNA of progressive pneumonia, maedi and visna viruses demonstrate that lung DNA from sheep afflicted with progressive interstitial pneumonia possesses virus-related sequences not present in normal sheep lung DNA."} {"id": "PMID:173795", "title": "On the mechanism of neurotropism of vesicular stomatitis virus in newborn hamsters. Studies with temperature-sensitive mutants.", "content": "The virulence of temperature-sensitive mutants of vesicular stomatitis virus (VSV) injected subcutaneously into newborn hamsters was positively correlated with their tendency to generate revertants and with their leakiness in cultured hamster embryo fibroblasts maintained at 37 degrees C, the measured body temperature of the animals under our experimental conditions. The complementation group of the mutants seemed important only in that it tended to determine reversion frequency and leakiness. One non-reverting group I mutant (T1026), however, was much less virulent than would be expected from its extreme leakiness at body temperature. The disease produced by the less virulent mutants was characterized by neurological symptoms and led to delayed death, unlike the rapid deatth produced by virulent mutants. Infectious virus could be found in higher titres in the brains than in peripheral organs of such animals (with ratios as high as 10(8)). This neurotropism was not correlated with the complementation group of the mutant but was shown to be the consequence of survival for more than 3 days after injection. Age was not responsible for the effect. Animals injected at birth with T1026 were completely resistant to subcutaneous superinfection with the highly virulent wildtype virus HR at 3 to 4 days, though non-T1026-protected animals were completely sensitive. When HR was injected intracerebrally at 3 to 4 days, the T1026-protected animals allowed replication to high titres in the brain but not in peripheral organs, whereas non-T1026-protected animals allowed replication to high titres in both brain and in peripheral organs. We suggest from these results that the observed neurotropism is produced by a resistance mechanism operative in peripheral organs but not in the brain; this resistance develops rapidly in newborn animals on exposure to virus and clears virus from the peripheral organs leaving it in the brain. It is possible that our effect represents a controlled and accelerated induction of the classical peripheral resistance of animals to various viruses which normally develops with age.", "contents": "On the mechanism of neurotropism of vesicular stomatitis virus in newborn hamsters. Studies with temperature-sensitive mutants. The virulence of temperature-sensitive mutants of vesicular stomatitis virus (VSV) injected subcutaneously into newborn hamsters was positively correlated with their tendency to generate revertants and with their leakiness in cultured hamster embryo fibroblasts maintained at 37 degrees C, the measured body temperature of the animals under our experimental conditions. The complementation group of the mutants seemed important only in that it tended to determine reversion frequency and leakiness. One non-reverting group I mutant (T1026), however, was much less virulent than would be expected from its extreme leakiness at body temperature. The disease produced by the less virulent mutants was characterized by neurological symptoms and led to delayed death, unlike the rapid deatth produced by virulent mutants. Infectious virus could be found in higher titres in the brains than in peripheral organs of such animals (with ratios as high as 10(8)). This neurotropism was not correlated with the complementation group of the mutant but was shown to be the consequence of survival for more than 3 days after injection. Age was not responsible for the effect. Animals injected at birth with T1026 were completely resistant to subcutaneous superinfection with the highly virulent wildtype virus HR at 3 to 4 days, though non-T1026-protected animals were completely sensitive. When HR was injected intracerebrally at 3 to 4 days, the T1026-protected animals allowed replication to high titres in the brain but not in peripheral organs, whereas non-T1026-protected animals allowed replication to high titres in both brain and in peripheral organs. We suggest from these results that the observed neurotropism is produced by a resistance mechanism operative in peripheral organs but not in the brain; this resistance develops rapidly in newborn animals on exposure to virus and clears virus from the peripheral organs leaving it in the brain. It is possible that our effect represents a controlled and accelerated induction of the classical peripheral resistance of animals to various viruses which normally develops with age."} {"id": "PMID:173796", "title": "Inhibition of interferon action by vitamin A.", "content": "Simultaneous treatment of mouse cells with interferon and vitamin A (retinoic acid) resulted in an inhibition of interferon action. Increasing concentrations of calf serum decreased the inhibitory effect of retinoic acid on interferon action. Treatment of interferon with retinoic acid prior to the assay for interferon activity also resulted in a loss of interferon activity. Since the residual retinoic acid present after dilution of the interferon for assay was not sufficient to interfere with the assay, it is presumed that interferon and retinoic acid must interact in some fashion to inhibit interferon activity. Calf serum prevented the apparent interaction of retinoic acid and interferon. The loss of interferon activity which resulted from treatment of interferon with retinoic acid was dependent on temperature and time of incubation. Retinyl acetate (acetate ester of vitamin A) and retinal (vitamin A adehyde) only slightly inhibited interferon activity, while retinoic acid (vitamin A acid) and retinol (vitamin A alcohol) were similarly effective at inhibiting interferon activity. Another fat soluble vitamin, vitamin K1, did not inhibit interferon activity.", "contents": "Inhibition of interferon action by vitamin A. Simultaneous treatment of mouse cells with interferon and vitamin A (retinoic acid) resulted in an inhibition of interferon action. Increasing concentrations of calf serum decreased the inhibitory effect of retinoic acid on interferon action. Treatment of interferon with retinoic acid prior to the assay for interferon activity also resulted in a loss of interferon activity. Since the residual retinoic acid present after dilution of the interferon for assay was not sufficient to interfere with the assay, it is presumed that interferon and retinoic acid must interact in some fashion to inhibit interferon activity. Calf serum prevented the apparent interaction of retinoic acid and interferon. The loss of interferon activity which resulted from treatment of interferon with retinoic acid was dependent on temperature and time of incubation. Retinyl acetate (acetate ester of vitamin A) and retinal (vitamin A adehyde) only slightly inhibited interferon activity, while retinoic acid (vitamin A acid) and retinol (vitamin A alcohol) were similarly effective at inhibiting interferon activity. Another fat soluble vitamin, vitamin K1, did not inhibit interferon activity."} {"id": "PMID:173797", "title": "Absence of poly (A) from the infective RNA of Nodamura virus.", "content": "With the exception of phage Qbeta, the RNAs of all the other small icosahedral RNA viruses so far examined contain a poly (A) tract. This tract has been implicated in the infectivity of poliovirus RNA. We have now shown that Nodamura virus, a divided genome virus from which infective RNA can be extracted, does not contain any poly (A) tracts. This evidence with Nodamura virus shows that poly (A) is not a necessary requirement for the infectivity of virus RNA molecules.", "contents": "Absence of poly (A) from the infective RNA of Nodamura virus. With the exception of phage Qbeta, the RNAs of all the other small icosahedral RNA viruses so far examined contain a poly (A) tract. This tract has been implicated in the infectivity of poliovirus RNA. We have now shown that Nodamura virus, a divided genome virus from which infective RNA can be extracted, does not contain any poly (A) tracts. This evidence with Nodamura virus shows that poly (A) is not a necessary requirement for the infectivity of virus RNA molecules."} {"id": "PMID:173798", "title": "DNA polymerase in pseudorabies virus infected cells.", "content": "The DNA polymerase activity in BHK 21/C13 cells infected with pseudorabies virus is inhibited by incubation with antiserum to pseudorabies but not by incubation with pre-immune serum or by antiserum to herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2). It also differs from the cell enzyme and the enzymes in HSV-1 or HSV-2 infected cells in its requirement for KCl in the in vitro assay. It seems likely, therefore, that pseudorabies virus specifies its own DNA polymerase.", "contents": "DNA polymerase in pseudorabies virus infected cells. The DNA polymerase activity in BHK 21/C13 cells infected with pseudorabies virus is inhibited by incubation with antiserum to pseudorabies but not by incubation with pre-immune serum or by antiserum to herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2). It also differs from the cell enzyme and the enzymes in HSV-1 or HSV-2 infected cells in its requirement for KCl in the in vitro assay. It seems likely, therefore, that pseudorabies virus specifies its own DNA polymerase."} {"id": "PMID:173799", "title": "Anti-viral activity of single-stranded homopolynucleotides against encephalomyocarditis virus and Semliki Forest virus in adult mice without interferon induction.", "content": "Single administrations of poly C or poly I are anti-viral against infections of encephalomyocarditis (EMC) and Semliki Forest virus (SFV) in mice but poly U and poly A are not. The degree of protection is dose-dependent and mice which die do so at a later time when untreated controls even in a strain of mouse in which the time of death is not dependent on the dose of virus given. No circulating interferon is found after treating mice with poly C or poly I even at polynucleotide doses which give the same degree of protection as the interferon inducer, poly I:C. Several additional features distinguish the protection by poly C and poly I from interferon induction: the effect is low 24h before infection and maximal 6 h before infection, the effect is short-lived and mice do not show hypo-reactivation to repeated treatment. Limited treatment of mice with poly I:C, interferon or poly C before infection itself results in additional protection when poly C is also administered after infection, indicating that poly C has an effect after onset of virus replication. After infection poly C and poly I are both more effective by the intravenous route but before infection they are most effective when administered by the same route as the virus. Quantitative comparisons of the protective effects of poly C, poly I and the interferon inducer, poly I:C, are possible from dose response curves of the polynucleotides at different times relative to infection and by different routes of administration. The results are considered in relation to the presence of homopolyribonucleotide tracts in the viral genomes and effects on the reticulo-endothelial system of the mice.", "contents": "Anti-viral activity of single-stranded homopolynucleotides against encephalomyocarditis virus and Semliki Forest virus in adult mice without interferon induction. Single administrations of poly C or poly I are anti-viral against infections of encephalomyocarditis (EMC) and Semliki Forest virus (SFV) in mice but poly U and poly A are not. The degree of protection is dose-dependent and mice which die do so at a later time when untreated controls even in a strain of mouse in which the time of death is not dependent on the dose of virus given. No circulating interferon is found after treating mice with poly C or poly I even at polynucleotide doses which give the same degree of protection as the interferon inducer, poly I:C. Several additional features distinguish the protection by poly C and poly I from interferon induction: the effect is low 24h before infection and maximal 6 h before infection, the effect is short-lived and mice do not show hypo-reactivation to repeated treatment. Limited treatment of mice with poly I:C, interferon or poly C before infection itself results in additional protection when poly C is also administered after infection, indicating that poly C has an effect after onset of virus replication. After infection poly C and poly I are both more effective by the intravenous route but before infection they are most effective when administered by the same route as the virus. Quantitative comparisons of the protective effects of poly C, poly I and the interferon inducer, poly I:C, are possible from dose response curves of the polynucleotides at different times relative to infection and by different routes of administration. The results are considered in relation to the presence of homopolyribonucleotide tracts in the viral genomes and effects on the reticulo-endothelial system of the mice."} {"id": "PMID:173800", "title": "Poliovirus proteins associated with the replication complex in infected cells.", "content": "Viral polypeptides associated with the membrane-free replication complex of poliovirus RNA were multiple in nature. The structural protein precursors [VP0, VP1, VP3] predominated, and because they were found in a cytoplasmic component with the same S value and density as the replication complex are likely to be attached to it in vivo. They were not present in the form of empty capsids. The electrophoretic polypeptide pattern of the membrane-bound replication complex was similar but showed a predominance of NCVPX or VP1, unless the cells were slightly depleted in amino acids when the non-structural polypeptide NCVP2 became important. Cystine was the only amino acid capable of reversing this depletion effect on its own.", "contents": "Poliovirus proteins associated with the replication complex in infected cells. Viral polypeptides associated with the membrane-free replication complex of poliovirus RNA were multiple in nature. The structural protein precursors [VP0, VP1, VP3] predominated, and because they were found in a cytoplasmic component with the same S value and density as the replication complex are likely to be attached to it in vivo. They were not present in the form of empty capsids. The electrophoretic polypeptide pattern of the membrane-bound replication complex was similar but showed a predominance of NCVPX or VP1, unless the cells were slightly depleted in amino acids when the non-structural polypeptide NCVP2 became important. Cystine was the only amino acid capable of reversing this depletion effect on its own."} {"id": "PMID:173801", "title": "[Poland's syndrome in a sterile woman].", "content": "In a woman aged 32, who came for consultation regarding her sterility, a case of Poland's syndrome was diagnosed in view of a brachysyndactylia and a homolateral agenesia of the large pectoral. The possible connexion between her sterility and this syndrome is discussed.", "contents": "[Poland's syndrome in a sterile woman]. In a woman aged 32, who came for consultation regarding her sterility, a case of Poland's syndrome was diagnosed in view of a brachysyndactylia and a homolateral agenesia of the large pectoral. The possible connexion between her sterility and this syndrome is discussed."} {"id": "PMID:173802", "title": "Studies on serotonin binding proteins of nerve ending membranes.", "content": "Synaptic membranes were isolated from rat brain homogenates by differential and density gradient centrifugation. Membrane proteins were solubilized by detergent buffer and assayed for serotonin-binding activity by adsorption of free 5-HT on charcoal. When the membrane extract was incubated with serotonin at +4 degrees C for various times, equilibrium was reached within 10 min. With increasing serotonin concentrations the specific part of binding was saturable whereas the non-specific part increased linear with the total 5-HT added. Kinetic analysis of the data revealed two different classes of binding sites with the apparent dissociation constants Kd1 = 5.3X10(-7) M and Kd2 = 1.1X10-5 M. The disociation reaction followed first order kinetics in two steps. The first step was very rapid, the second step proceeded with a half life time t1/2 of 16 min and a dissociation rate constant of k-1 = 7.2X10(-4) s-1. the binding was sensitive to heat and SH-blocking reagents and displaceable by serotonin in excess, d-LSD, and to a lower extent by 5-methoxytryptamine and tryptamine. The significance and localization of the binding sites at the membrane are discussed.", "contents": "Studies on serotonin binding proteins of nerve ending membranes. Synaptic membranes were isolated from rat brain homogenates by differential and density gradient centrifugation. Membrane proteins were solubilized by detergent buffer and assayed for serotonin-binding activity by adsorption of free 5-HT on charcoal. When the membrane extract was incubated with serotonin at +4 degrees C for various times, equilibrium was reached within 10 min. With increasing serotonin concentrations the specific part of binding was saturable whereas the non-specific part increased linear with the total 5-HT added. Kinetic analysis of the data revealed two different classes of binding sites with the apparent dissociation constants Kd1 = 5.3X10(-7) M and Kd2 = 1.1X10-5 M. The disociation reaction followed first order kinetics in two steps. The first step was very rapid, the second step proceeded with a half life time t1/2 of 16 min and a dissociation rate constant of k-1 = 7.2X10(-4) s-1. the binding was sensitive to heat and SH-blocking reagents and displaceable by serotonin in excess, d-LSD, and to a lower extent by 5-methoxytryptamine and tryptamine. The significance and localization of the binding sites at the membrane are discussed."} {"id": "PMID:173805", "title": "Comparison of the intermediary metabolism of fatty acids in denervated and dystrophic murine skeletal muscle.", "content": "Certain aspects of lipid metabolism have been examined in denervated muscle from normal mice and in dystrophic muscle from mice of the Bar Harbor strain 129. A number of parameters show no change or similar changes. For example, the utilization of palmitate-[1-14C] and palmitylcarnitine by mitochondria from denervated and dystrophic hind leg skeletal muscle showed parallel decreased in the oxidation of palmitate (30-42%) and palmitylcarnite (37-66%). A comparable study with acetylcarnitine showed a striking difference with no change evident in mitochondria from denervated muscle and 80-85% decrease in dystrophic muscle. The study of succinate dehydrogenase and the enzymes of beta-oxidation in the above mitochondrial preparation showed similar findings except for acyl CoA dehydrogenase activity (an enzyme with a regulatory role in beta-oxidation) which was significantly diminished (29%) in denervated muscle, whereas no change was observed in dystrophic muscle. The findings show a close parallel in a number of parameters but distinct differences were observed in denervated as compared with dystrophic muscle. It is unlikely that the muscular disorder in murine muscular dystrophy can be explained solely on the basis of denervation or the loss of a neural trophic factor.", "contents": "Comparison of the intermediary metabolism of fatty acids in denervated and dystrophic murine skeletal muscle. Certain aspects of lipid metabolism have been examined in denervated muscle from normal mice and in dystrophic muscle from mice of the Bar Harbor strain 129. A number of parameters show no change or similar changes. For example, the utilization of palmitate-[1-14C] and palmitylcarnitine by mitochondria from denervated and dystrophic hind leg skeletal muscle showed parallel decreased in the oxidation of palmitate (30-42%) and palmitylcarnite (37-66%). A comparable study with acetylcarnitine showed a striking difference with no change evident in mitochondria from denervated muscle and 80-85% decrease in dystrophic muscle. The study of succinate dehydrogenase and the enzymes of beta-oxidation in the above mitochondrial preparation showed similar findings except for acyl CoA dehydrogenase activity (an enzyme with a regulatory role in beta-oxidation) which was significantly diminished (29%) in denervated muscle, whereas no change was observed in dystrophic muscle. The findings show a close parallel in a number of parameters but distinct differences were observed in denervated as compared with dystrophic muscle. It is unlikely that the muscular disorder in murine muscular dystrophy can be explained solely on the basis of denervation or the loss of a neural trophic factor."} {"id": "PMID:173806", "title": "Early onset myotonic dystrophy in association with polyneuropathy.", "content": "A patient with early onset of myotonic dystrophy, with associated neuropathy and epilepsy, is presented. It is postulated that his disorder was inherited through a recessive, pleomorphic gene. His differential diagnosis is discussed and the literature reviewed. The clinical variability of myotonic dystrophy is stressed and the diagnostic difficulties encountered in the younger age group.", "contents": "Early onset myotonic dystrophy in association with polyneuropathy. A patient with early onset of myotonic dystrophy, with associated neuropathy and epilepsy, is presented. It is postulated that his disorder was inherited through a recessive, pleomorphic gene. His differential diagnosis is discussed and the literature reviewed. The clinical variability of myotonic dystrophy is stressed and the diagnostic difficulties encountered in the younger age group."} {"id": "PMID:173807", "title": "Immunological differential diagnosis of human brain tumours.", "content": "Results of immunological experiments with various human brain tumours show differences between astrocytoma and glioblastoma multiforme when brain-specific alpha2-glycoprotein is used as an immunological marker. On this basis a tentative model of cytogenesis and oncogenic transformation of glial cells was presented. Morphological resemblances between the brain-specific alpha2-glycoprotein immuno-precipitation lines obtained from astrocytoma cells and from normal cerebral white matter treated with neuraminidase are discussed in relation to experimental and clinical studies of tumour cells treated with neuraminidase.", "contents": "Immunological differential diagnosis of human brain tumours. Results of immunological experiments with various human brain tumours show differences between astrocytoma and glioblastoma multiforme when brain-specific alpha2-glycoprotein is used as an immunological marker. On this basis a tentative model of cytogenesis and oncogenic transformation of glial cells was presented. Morphological resemblances between the brain-specific alpha2-glycoprotein immuno-precipitation lines obtained from astrocytoma cells and from normal cerebral white matter treated with neuraminidase are discussed in relation to experimental and clinical studies of tumour cells treated with neuraminidase."} {"id": "PMID:173808", "title": "Hereditary demyelinating neuropathy in the trembler mouse.", "content": "The Trembler mouse suffers from a hereditary demyelinating neuropathy. Nerve conduction studies were performed on the sciatic nerve, median nerve and dorsal nerve of the tail. There was a prolonged terminal latency, and motor conduction velocities were less than 10 m/sec in all the nerves examined. The electrophysiological abnormalities correlate with the pathological findings of hypomyelination.", "contents": "Hereditary demyelinating neuropathy in the trembler mouse. The Trembler mouse suffers from a hereditary demyelinating neuropathy. Nerve conduction studies were performed on the sciatic nerve, median nerve and dorsal nerve of the tail. There was a prolonged terminal latency, and motor conduction velocities were less than 10 m/sec in all the nerves examined. The electrophysiological abnormalities correlate with the pathological findings of hypomyelination."} {"id": "PMID:173809", "title": "Neurological complication of antirabies vaccination in S\u00e3o Paulo, Brazil. Clinical and therapeutical aspects.", "content": "The author studied especially the clinical aspects and therapeutic results in 73 patients with neurological complication of anti-rabies vaccination. The neuroparalytic accidents and the most constant neurologic signs and symptoms were emphasized. The most common clinical syndrome was thoraco-lumbar meningomyelitis and there were CSF alterations in 88% of the cases studied. Eighteen patients presented neurologic complications after Fuenzalida vaccine: only 1 of them had Guillain-Barr\u00e9 syndrome, 1 had meningoradiculitis, 4 had myelitis and in the other 12 cases there was diffuse involvement of the nervous system especially of the spinal cord and meninges (meningomyelitis and meningoencephalomyelitis).", "contents": "Neurological complication of antirabies vaccination in S\u00e3o Paulo, Brazil. Clinical and therapeutical aspects. The author studied especially the clinical aspects and therapeutic results in 73 patients with neurological complication of anti-rabies vaccination. The neuroparalytic accidents and the most constant neurologic signs and symptoms were emphasized. The most common clinical syndrome was thoraco-lumbar meningomyelitis and there were CSF alterations in 88% of the cases studied. Eighteen patients presented neurologic complications after Fuenzalida vaccine: only 1 of them had Guillain-Barr\u00e9 syndrome, 1 had meningoradiculitis, 4 had myelitis and in the other 12 cases there was diffuse involvement of the nervous system especially of the spinal cord and meninges (meningomyelitis and meningoencephalomyelitis)."} {"id": "PMID:173810", "title": "Retroperitoneal ganglioneuroblastoma: a kaleidoscope of neuronal degeneration. A light and electron microscopic study.", "content": "The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence for their non-specificity. Although the pathogenesis of the membranous cytoplasmic bodies in this tumor is unclear, they ostensibly arise within endoplasmic cisterns, similar to the proposed origin of membranous cytoplasmic bodies in Tay-Sachs disease. Both the apparent continuum between argyrophilic bodies and central chromatolysis, and the incorporation of various cytoplasmic constituents within neurofilamentous proliferations reflect some of the dynamic factors involved in the formation of Pick bodies.", "contents": "Retroperitoneal ganglioneuroblastoma: a kaleidoscope of neuronal degeneration. A light and electron microscopic study. The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence for their non-specificity. Although the pathogenesis of the membranous cytoplasmic bodies in this tumor is unclear, they ostensibly arise within endoplasmic cisterns, similar to the proposed origin of membranous cytoplasmic bodies in Tay-Sachs disease. Both the apparent continuum between argyrophilic bodies and central chromatolysis, and the incorporation of various cytoplasmic constituents within neurofilamentous proliferations reflect some of the dynamic factors involved in the formation of Pick bodies."} {"id": "PMID:173811", "title": "Light-cored dense particles in mitochondria of a patient with skeletal muscle and myocardial disease.", "content": "A 15-year-old boy with skeletal muscle and myocardial disease was found to have large numbers of abnormal muscle mitochondria, the distinguishing feature of which was the presence of many light-cored dense particles. These particles bore a marked resemblance to those seen in situations where mitochondria accumulate calcium. If that is what they were, it remains to be determined whether such an accumulation of calcium, or other mitochondrial abnormality, played a role in the patient's muscle weakness. Alternatively, the granules might have represented evidence of virus involvement of the mitochondria, but this seems less likely.", "contents": "Light-cored dense particles in mitochondria of a patient with skeletal muscle and myocardial disease. A 15-year-old boy with skeletal muscle and myocardial disease was found to have large numbers of abnormal muscle mitochondria, the distinguishing feature of which was the presence of many light-cored dense particles. These particles bore a marked resemblance to those seen in situations where mitochondria accumulate calcium. If that is what they were, it remains to be determined whether such an accumulation of calcium, or other mitochondrial abnormality, played a role in the patient's muscle weakness. Alternatively, the granules might have represented evidence of virus involvement of the mitochondria, but this seems less likely."} {"id": "PMID:173812", "title": "The fine structure of astrocytes in the adult staggerer.", "content": "The fine structure of the cerebella of staggerer mice was studied. Particular attention was paid to the astrocytic processes which showed characteristic changes in the adult animal. These consisted of parallel configurations of slender sheet-like astrocytic processes frequently connected to one another by highly organized intercellular adhesive devices. The abnormal condition seen in staggerer is an exaggerated expression of the fundamental tendency of the astrocyte to form sheet-like peripheral processes.", "contents": "The fine structure of astrocytes in the adult staggerer. The fine structure of the cerebella of staggerer mice was studied. Particular attention was paid to the astrocytic processes which showed characteristic changes in the adult animal. These consisted of parallel configurations of slender sheet-like astrocytic processes frequently connected to one another by highly organized intercellular adhesive devices. The abnormal condition seen in staggerer is an exaggerated expression of the fundamental tendency of the astrocyte to form sheet-like peripheral processes."} {"id": "PMID:173813", "title": "Management of the uninhibited bladder by selective sacral neurectomy.", "content": "The authors report the treatment of incontinence due to uninhibited bladder contractions by selective sacral neurectomy in nine patients, four without evidence of neurological disease. A detailed and objective analysis of bladder and urethral function, together with quantitation of clinical features, was made before and after operation. Seven patients were either cured or greatly improved. The overall increase in bladder capacity and reduction of uninhibited activity were statistically significant. The resting urethral sphincter pressure was unchanged, but the contractility of the voluntary external sphincter was slightly impaired. Criteria for such neurectomies are discussed.", "contents": "Management of the uninhibited bladder by selective sacral neurectomy. The authors report the treatment of incontinence due to uninhibited bladder contractions by selective sacral neurectomy in nine patients, four without evidence of neurological disease. A detailed and objective analysis of bladder and urethral function, together with quantitation of clinical features, was made before and after operation. Seven patients were either cured or greatly improved. The overall increase in bladder capacity and reduction of uninhibited activity were statistically significant. The resting urethral sphincter pressure was unchanged, but the contractility of the voluntary external sphincter was slightly impaired. Criteria for such neurectomies are discussed."} {"id": "PMID:173814", "title": "Controlled study of CCNU and radiation therapy in malignant astrocytoma.", "content": "The authors report 63 patients with biopsy-proved malignant (Grades 3 and 4) astrocytomas who were randomly placed in one of three treatment schedules within 2 weeks of surgery. One group (22 patients) received radiation therapy alone; the second group (22 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) orally at intervals of 8 weeks; and the third group (19 patients) received combined radiation and drug therapy. Patients who received radiation therapy, with or without the drug, had a significantly longer survival than did those who received the drug alone. There was no difference in survival between the two groups who received radiation. The nitrosourea derivative CCNU does not seem to be an effective agent in the therapy of primary malignant brain tumors.", "contents": "Controlled study of CCNU and radiation therapy in malignant astrocytoma. The authors report 63 patients with biopsy-proved malignant (Grades 3 and 4) astrocytomas who were randomly placed in one of three treatment schedules within 2 weeks of surgery. One group (22 patients) received radiation therapy alone; the second group (22 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) orally at intervals of 8 weeks; and the third group (19 patients) received combined radiation and drug therapy. Patients who received radiation therapy, with or without the drug, had a significantly longer survival than did those who received the drug alone. There was no difference in survival between the two groups who received radiation. The nitrosourea derivative CCNU does not seem to be an effective agent in the therapy of primary malignant brain tumors."} {"id": "PMID:173815", "title": "Increased localization of 99mTc-pyrophosphate in a bone island: case report.", "content": "A positive 99mTc-pyrophosphate bone scan is reported in a proven case of large compact bone island. Pyrophosphate uptake in this case is presumed to be due to either large size or growth of the bone island. A radionuclide bone scan does not always differentiate bone islands from metastatic or inflammatory sclerotic bone lesions.", "contents": "Increased localization of 99mTc-pyrophosphate in a bone island: case report. A positive 99mTc-pyrophosphate bone scan is reported in a proven case of large compact bone island. Pyrophosphate uptake in this case is presumed to be due to either large size or growth of the bone island. A radionuclide bone scan does not always differentiate bone islands from metastatic or inflammatory sclerotic bone lesions."} {"id": "PMID:173816", "title": "Comparison of 18F and 99mTc-polyphosphate in orthopedic bone scintigraphy.", "content": "To compare 99mTc-polyphosphate and 18F for use in orthopedics, 79 patients were examined with both. Fifty cases were suitable for analysis. While the extraskeletal uptake of 18F was found to be negligible, 99mTc-polyphosphate may accumulate considerably in pathologic soft tissue, e.g., in soft-tissue tumors and in inflamed synovial tissue. This soft-tissue Tc accumulation may obscure the osseus uptake, notably in the examination of joint regions, commonly the regions of interest in orthopedics. After simultaneous administration of both agents, quantitative measurements were performed on specimens of bone and synovial tissue from diseased joints in human patients and in rabbits. The uptake of 99mTc-polyphosphate in synovial tissue was shown to be about seven times that of 18F, while their uptakes in bone were equal. In short, 99mTc-polyphosphate, a valuable tracer in general, is hardly the agent of choice in orthopedics.", "contents": "Comparison of 18F and 99mTc-polyphosphate in orthopedic bone scintigraphy. To compare 99mTc-polyphosphate and 18F for use in orthopedics, 79 patients were examined with both. Fifty cases were suitable for analysis. While the extraskeletal uptake of 18F was found to be negligible, 99mTc-polyphosphate may accumulate considerably in pathologic soft tissue, e.g., in soft-tissue tumors and in inflamed synovial tissue. This soft-tissue Tc accumulation may obscure the osseus uptake, notably in the examination of joint regions, commonly the regions of interest in orthopedics. After simultaneous administration of both agents, quantitative measurements were performed on specimens of bone and synovial tissue from diseased joints in human patients and in rabbits. The uptake of 99mTc-polyphosphate in synovial tissue was shown to be about seven times that of 18F, while their uptakes in bone were equal. In short, 99mTc-polyphosphate, a valuable tracer in general, is hardly the agent of choice in orthopedics."} {"id": "PMID:173817", "title": "Stoppage of glycogenesis and \"over-shoot\" of induction of lipogenesis and its related enzyme activities in the liver of fasted-refed rats.", "content": "To elucidate the causes of changes of carbohydrate metabolic pathways, the time course of utilization of dietary [U-14C]sucrose and induction of enzyme activities in the livers of rats were investigated. Adult male rats of BHE strain were refed after a fast of 2 days. The nutritionally complete refeeding diet contained 60% sucrose as the only source of carbohydrate. [U-14C]Sucrose was included in the diet on either day 1 or day 2, or both of refeeding. During the first day of refeeding, the radioactivity was incorporated mainly into liver glycogen which rose to over 100 mg/g. During the second day, little 14C appeared in the liver glycogen, which decreased sharply while glucose-6-phosphatase activity increased. The glycogenic pathway thus appeared to be blocked. On the other hand, 14C incorporation in the liver fat was minimal during the first day, but was quite extensive during the second day of refeeding. The enhanced lipogenesis was accompanied by large increases of activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-malic dehydrogenase. Results clearly indicate that the carbohydrate load in the liver of intact animals was initially metabolized by the glycogenic pathway. When glycogenesis stopped, carbohydrate was metabolized differently. The enhanced incorporation of [U-14C]sucrose into liver lipids indicates an increased formation of acetyl CoA and an accelerated formation and use of NADPH, probably from increasing dehydrogenase activities. Our data suggest that the blockage of synthesis of glycogen with the continuation of carbohydrate load was a primary cause in over-shooting induction of hepatic dehydrogenase activities and lipogenesis.", "contents": "Stoppage of glycogenesis and \"over-shoot\" of induction of lipogenesis and its related enzyme activities in the liver of fasted-refed rats. To elucidate the causes of changes of carbohydrate metabolic pathways, the time course of utilization of dietary [U-14C]sucrose and induction of enzyme activities in the livers of rats were investigated. Adult male rats of BHE strain were refed after a fast of 2 days. The nutritionally complete refeeding diet contained 60% sucrose as the only source of carbohydrate. [U-14C]Sucrose was included in the diet on either day 1 or day 2, or both of refeeding. During the first day of refeeding, the radioactivity was incorporated mainly into liver glycogen which rose to over 100 mg/g. During the second day, little 14C appeared in the liver glycogen, which decreased sharply while glucose-6-phosphatase activity increased. The glycogenic pathway thus appeared to be blocked. On the other hand, 14C incorporation in the liver fat was minimal during the first day, but was quite extensive during the second day of refeeding. The enhanced lipogenesis was accompanied by large increases of activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-malic dehydrogenase. Results clearly indicate that the carbohydrate load in the liver of intact animals was initially metabolized by the glycogenic pathway. When glycogenesis stopped, carbohydrate was metabolized differently. The enhanced incorporation of [U-14C]sucrose into liver lipids indicates an increased formation of acetyl CoA and an accelerated formation and use of NADPH, probably from increasing dehydrogenase activities. Our data suggest that the blockage of synthesis of glycogen with the continuation of carbohydrate load was a primary cause in over-shooting induction of hepatic dehydrogenase activities and lipogenesis."} {"id": "PMID:173818", "title": "Gluconeogenic response to mannoheptulose in the rat.", "content": "Since administration of mannoheptulose induces temporary hyperglycemia, the present study was conducted to elucidate this phenomenon. The results indicate that mannoheptulose stimulates the activity of hepatic fructose-1,6-diphosphatase and phosphoenolpyruvate carboxykinase, and enhances incorporation of alanine into blood glucose and hepatic glycogen. In addition, mannoheptulose increases plasma levels of glucagon and hepatic cyclic AMP concentration. Gluconeogenic effects of mannoheptulose appear to be mediated by glucagon.", "contents": "Gluconeogenic response to mannoheptulose in the rat. Since administration of mannoheptulose induces temporary hyperglycemia, the present study was conducted to elucidate this phenomenon. The results indicate that mannoheptulose stimulates the activity of hepatic fructose-1,6-diphosphatase and phosphoenolpyruvate carboxykinase, and enhances incorporation of alanine into blood glucose and hepatic glycogen. In addition, mannoheptulose increases plasma levels of glucagon and hepatic cyclic AMP concentration. Gluconeogenic effects of mannoheptulose appear to be mediated by glucagon."} {"id": "PMID:173819", "title": "Mechanism and regulation of thiamine pyrophosphokinase from parsely leaf.", "content": "Thiamine pyrophosphokinase (EC 2.7.6.2) from parsely leaf showed an absolute requirement for divalent cation such as Mg2+, Mn2+ and Co2+. The activation effect varied with the species and concentrations of such cations. When Mn2+ or Co2+ was used as cofactor, maximal activation was found at a lower level than ATP concentration, whereas the activation by Mg2+ increased hyperbolically with the concentration. Studies of initial velocity and product inhibition led to conclude that the kinase reaction obeys a sequential ordered Bi Bi mechanism; i.e. the enzyme combines in turns with MgATP and thiamine, followed by release of TPP and AMP. The inhibition type revealed for inorganic pyrophosphate was competitive with respect to thiamine with Ki of approximately 2.8 mM. On the other hand, thiamine monophosphate exhibited noncompetitive inhibition with Ki of 0.2 mM. The plots of the reaction rate against MgATP concentrations gave a sigmoidal curve. Addition of either AMP or GMP resulted in restoration of a depressed activity at low concentration of MgATP. The \"allosteric\" inhibition was also relieved by the addition of an excess amount of magnesium ions. These findings suggest that transphosphorylation is regulated by subcellular concentrations of metal ions relative to ATP or of the products involved in the thiamine biosynthesis.", "contents": "Mechanism and regulation of thiamine pyrophosphokinase from parsely leaf. Thiamine pyrophosphokinase (EC 2.7.6.2) from parsely leaf showed an absolute requirement for divalent cation such as Mg2+, Mn2+ and Co2+. The activation effect varied with the species and concentrations of such cations. When Mn2+ or Co2+ was used as cofactor, maximal activation was found at a lower level than ATP concentration, whereas the activation by Mg2+ increased hyperbolically with the concentration. Studies of initial velocity and product inhibition led to conclude that the kinase reaction obeys a sequential ordered Bi Bi mechanism; i.e. the enzyme combines in turns with MgATP and thiamine, followed by release of TPP and AMP. The inhibition type revealed for inorganic pyrophosphate was competitive with respect to thiamine with Ki of approximately 2.8 mM. On the other hand, thiamine monophosphate exhibited noncompetitive inhibition with Ki of 0.2 mM. The plots of the reaction rate against MgATP concentrations gave a sigmoidal curve. Addition of either AMP or GMP resulted in restoration of a depressed activity at low concentration of MgATP. The \"allosteric\" inhibition was also relieved by the addition of an excess amount of magnesium ions. These findings suggest that transphosphorylation is regulated by subcellular concentrations of metal ions relative to ATP or of the products involved in the thiamine biosynthesis."} {"id": "PMID:173820", "title": "Glycerolipid metabolism in cellular and subcellular fractions of fasted rat liver.", "content": "The effect of overnight fasting on glycerolipids of the rat liver organelles was studied. The concentration of microsomal phospholipids was markedly decreased by fasting, whereas that of mitochondria and whole liver increased significantly. The significant increase due to fasting in the activity of microsomal phosphorylcholine-glyceride transferase appeared to be responsible for the increased concentration of hepatic phospholipid. The incorporation by the liver slice of [1(-14)C] glycerol into PC3 in mitochondria was increased by fasting, while there was no difference in the microsomal fraction containing supernatant. The significant decrease in the relative proportions of oleic and linoleic acids and a significant increase in stearic and arachidonic acids in phosphatidylcholine were observed in the intact liver as well as its subcellular fractions. The possible relationship of these changes after fasting to the similarity in the incorporation pattern of [1(-14)C] glycerol into the molecular species of these glycerolipids was demonstrated.", "contents": "Glycerolipid metabolism in cellular and subcellular fractions of fasted rat liver. The effect of overnight fasting on glycerolipids of the rat liver organelles was studied. The concentration of microsomal phospholipids was markedly decreased by fasting, whereas that of mitochondria and whole liver increased significantly. The significant increase due to fasting in the activity of microsomal phosphorylcholine-glyceride transferase appeared to be responsible for the increased concentration of hepatic phospholipid. The incorporation by the liver slice of [1(-14)C] glycerol into PC3 in mitochondria was increased by fasting, while there was no difference in the microsomal fraction containing supernatant. The significant decrease in the relative proportions of oleic and linoleic acids and a significant increase in stearic and arachidonic acids in phosphatidylcholine were observed in the intact liver as well as its subcellular fractions. The possible relationship of these changes after fasting to the similarity in the incorporation pattern of [1(-14)C] glycerol into the molecular species of these glycerolipids was demonstrated."} {"id": "PMID:173825", "title": "Testosterone treatment of excessively tall boys.", "content": "Twenty-nine tall boys with a mean height prediction of 198 cm were treated for serious psychosocial reasons with high doses of a long-acting testosterone preparation (500 mg/m2/month). Their ages at the start of treatment ranged from 9.8 to 16.9 years, and the mean duration of treatment was 1.2 years. Bone age was assessed according to the Tanner-Whitehouse II (RUS) method, and height predictions were calculated using the age-specific regression equations of Tanner and colleagues. On the basis of bone age at the start of treatment, three groups were formed (bone age 12.1 to 14, 14.1 to 15, and greater than 15 years), and the results were assessed separately. In the whole series, adult height was reduced by 5.4 cm; the best results (8cm) were achieved in the youngest bone age group. Under treatment, bone maturation was accelerated (1.8 years per year) and growth velocity increased (youngest bone age group) or was normal (older bone age groups). Testicular volume remained prepubertal in young patients and decreased in older ones. After discontinuation of treatment, testicular volume and sperm count became normal again after a mean period of 1.5 years, but in a few cases recovery was slower. It is concluded that adult height in tall boys may be effectively reduced by testosterone, that the results are best if treatment is started in early puberty, and that the suppressing effects on pituitary and testicular function are fully reversible. Since the indication for treatment is a psychosocial one, the patients should be carefully selected, taking into account not only growth but also psychological and familial factors.", "contents": "Testosterone treatment of excessively tall boys. Twenty-nine tall boys with a mean height prediction of 198 cm were treated for serious psychosocial reasons with high doses of a long-acting testosterone preparation (500 mg/m2/month). Their ages at the start of treatment ranged from 9.8 to 16.9 years, and the mean duration of treatment was 1.2 years. Bone age was assessed according to the Tanner-Whitehouse II (RUS) method, and height predictions were calculated using the age-specific regression equations of Tanner and colleagues. On the basis of bone age at the start of treatment, three groups were formed (bone age 12.1 to 14, 14.1 to 15, and greater than 15 years), and the results were assessed separately. In the whole series, adult height was reduced by 5.4 cm; the best results (8cm) were achieved in the youngest bone age group. Under treatment, bone maturation was accelerated (1.8 years per year) and growth velocity increased (youngest bone age group) or was normal (older bone age groups). Testicular volume remained prepubertal in young patients and decreased in older ones. After discontinuation of treatment, testicular volume and sperm count became normal again after a mean period of 1.5 years, but in a few cases recovery was slower. It is concluded that adult height in tall boys may be effectively reduced by testosterone, that the results are best if treatment is started in early puberty, and that the suppressing effects on pituitary and testicular function are fully reversible. Since the indication for treatment is a psychosocial one, the patients should be carefully selected, taking into account not only growth but also psychological and familial factors."} {"id": "PMID:173826", "title": "Childhood cancer in sibs.", "content": "Thirty-eight families with cancer in two or more children were identified from records of the Sidney Farber Cancer Center and the Children's Hospital, Boston. Neoplasms developed in one pair of identical twins and in 37 sets of sibs (2 with 4 affected sibs, 4 with 3, and 31 sib-pairs). Predisposition to cancer extended to their parents and other relatives, and subsequently to other sibs who were unaffected at the time of ascertainment of the cancer-prone families. Genetic susceptibility was suggested in individual families by parental consanguinity or by an inherited disorder predisposing to cancer, but in other instances no oncogenic factors were identified. Familial aggregates of childhood provide opportunities for etiologic study and cancer control.", "contents": "Childhood cancer in sibs. Thirty-eight families with cancer in two or more children were identified from records of the Sidney Farber Cancer Center and the Children's Hospital, Boston. Neoplasms developed in one pair of identical twins and in 37 sets of sibs (2 with 4 affected sibs, 4 with 3, and 31 sib-pairs). Predisposition to cancer extended to their parents and other relatives, and subsequently to other sibs who were unaffected at the time of ascertainment of the cancer-prone families. Genetic susceptibility was suggested in individual families by parental consanguinity or by an inherited disorder predisposing to cancer, but in other instances no oncogenic factors were identified. Familial aggregates of childhood provide opportunities for etiologic study and cancer control."} {"id": "PMID:173827", "title": "The occurrence of hepatoma in the chronic form of hereditary tyrosinemia.", "content": "A 5 1/2-year-old child with hepatocarcinoma complicating hereditary tyrosinemia is presented. A review of the literature and an attempted follow-up of previously reported patients with the chronic form of hereditary tyrosinemia have disclosed 16 cases of hepatocarcinoma occurring in 43 patients surviving beyond 2 years of age (37%). This incidence is considerably higher than that generally given for the occurrence of hepatoma in adults with macronodular cirrhosis. Females and males are equally at risk. Additional factors beyond the development of cirrhosis are likely operative in the induction of hepatocarcinoma in patients with this metabolic disorder; those surviving beyond infancy are at considerable risk for the development of fatal hepatic neoplasms.", "contents": "The occurrence of hepatoma in the chronic form of hereditary tyrosinemia. A 5 1/2-year-old child with hepatocarcinoma complicating hereditary tyrosinemia is presented. A review of the literature and an attempted follow-up of previously reported patients with the chronic form of hereditary tyrosinemia have disclosed 16 cases of hepatocarcinoma occurring in 43 patients surviving beyond 2 years of age (37%). This incidence is considerably higher than that generally given for the occurrence of hepatoma in adults with macronodular cirrhosis. Females and males are equally at risk. Additional factors beyond the development of cirrhosis are likely operative in the induction of hepatocarcinoma in patients with this metabolic disorder; those surviving beyond infancy are at considerable risk for the development of fatal hepatic neoplasms."} {"id": "PMID:173828", "title": "Noradrenergic subsensitivity and supersensitivity of the cerebral cortex after reserpine treatment.", "content": "Changes in the sensitivity of the cyclic adenosine 3', 5'-monophosphate response of rat brain cerebral cortical slices to norepinephrine were measured in vitro after the rats received i.p. injections of reserpine (1 mg/kg). Subsensitivity was evident 1 hour after a single reserpine treatment compared with saline controls. However, if reserpine was injected daily for 4 days followed by 1 day without reserpine treatment, a supersensitive response to NE was shown compared to the controls. Mean pD2 values are presented to illustrate the shifts of the dose-response curves after reserpine treatment. The present work demonstrated the induction of noradrenergic sub- and supersensitivity to norepinephrine in rat cerebral cortical slices after acute and 4-day reserpine treatment, respectively.", "contents": "Noradrenergic subsensitivity and supersensitivity of the cerebral cortex after reserpine treatment. Changes in the sensitivity of the cyclic adenosine 3', 5'-monophosphate response of rat brain cerebral cortical slices to norepinephrine were measured in vitro after the rats received i.p. injections of reserpine (1 mg/kg). Subsensitivity was evident 1 hour after a single reserpine treatment compared with saline controls. However, if reserpine was injected daily for 4 days followed by 1 day without reserpine treatment, a supersensitive response to NE was shown compared to the controls. Mean pD2 values are presented to illustrate the shifts of the dose-response curves after reserpine treatment. The present work demonstrated the induction of noradrenergic sub- and supersensitivity to norepinephrine in rat cerebral cortical slices after acute and 4-day reserpine treatment, respectively."} {"id": "PMID:173829", "title": "Effect of ethanol on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine-3',5'-monophosphate and theophylline.", "content": "The effects of ethanol on the water permeability and short-circuit current of the isolated urinary bladder of the toad, Bufo marinus, were investigated. Ethanol alone did not alter the flow of water along an osmotic gradient. The increase in osmotic water flow caused by vasopressin, theophylline or cyclic adenosine-3',5'-monophosphate was inhibited by 4 to 40 mg per ml of ethanol in the mucosal or serosal bathing medium. The inhibition was more marked when ethanol was added to the serosal bathing medium, in spite of the increase in the osmotic gradient across the toad bladder caused by the ethanol. Ethanol had no effect on the increase in sodium transport (short-circuit current) due to vasopressin, although there was a significant inhibition of base-line short-circuit current. It is possible that the water diuresis due to ethanol may result in part from an inhibition of the effect of vasopressin on the collecting duct.", "contents": "Effect of ethanol on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine-3',5'-monophosphate and theophylline. The effects of ethanol on the water permeability and short-circuit current of the isolated urinary bladder of the toad, Bufo marinus, were investigated. Ethanol alone did not alter the flow of water along an osmotic gradient. The increase in osmotic water flow caused by vasopressin, theophylline or cyclic adenosine-3',5'-monophosphate was inhibited by 4 to 40 mg per ml of ethanol in the mucosal or serosal bathing medium. The inhibition was more marked when ethanol was added to the serosal bathing medium, in spite of the increase in the osmotic gradient across the toad bladder caused by the ethanol. Ethanol had no effect on the increase in sodium transport (short-circuit current) due to vasopressin, although there was a significant inhibition of base-line short-circuit current. It is possible that the water diuresis due to ethanol may result in part from an inhibition of the effect of vasopressin on the collecting duct."} {"id": "PMID:173830", "title": "Effect of synaptic transmission blockade on morphine action in the guinea-pig myenteric plexus.", "content": "Morphine, which inhibits release of acetylcholine from neurons in the myenteric plexus, also inhibits the spontaneous electrical activity of some myenteric neurons. To determine whether morphine acts at a site presynaptic to these neurons, we investigated this morphine effect under conditions of synaptic transmission blockade. Synaptically driven action potentials evoked by point stimulation were recorded extracellularly, and it was shown that all synaptic responses were eliminated or greatly reduced in Ca-free, high-Mg Ringer's with ethylenebis [(oxyethylenenitrilo)]-tetraacetic acid (EGTA), suggesting that synaptic transmission was blocked. Under these conditions, the ability of morphine to inhibit spontaneous electrical activity was virtually unimpaired. Assuming a single locus of narcotic action in the myenteric plexus, it is unlikely, therefore, that the primary action of opiates is to stimulate release of an inhibitory transmitter, to prevent release of an excitatory transmitter or to block the postsynaptic receptor for an excitatory transmitter. Rather, opiates may raise the membrane threshold of a class of neurons. Electric field stimulation activates myenteric neurons, resulting in a morphine-sensitive release of acetylcholine and a contraction of the longitudinal muscle. The ability of field stimulation to induce contractions and of morphine to inhibit these contractions, was virtually unchanged when the only two known excitatory inputs to the cholinergic motor neuron were eliminated by receptor blockade. These observations, taken together, suggest that opiates act directly on the cholinergic motor neuron of the myenteric plexus.", "contents": "Effect of synaptic transmission blockade on morphine action in the guinea-pig myenteric plexus. Morphine, which inhibits release of acetylcholine from neurons in the myenteric plexus, also inhibits the spontaneous electrical activity of some myenteric neurons. To determine whether morphine acts at a site presynaptic to these neurons, we investigated this morphine effect under conditions of synaptic transmission blockade. Synaptically driven action potentials evoked by point stimulation were recorded extracellularly, and it was shown that all synaptic responses were eliminated or greatly reduced in Ca-free, high-Mg Ringer's with ethylenebis [(oxyethylenenitrilo)]-tetraacetic acid (EGTA), suggesting that synaptic transmission was blocked. Under these conditions, the ability of morphine to inhibit spontaneous electrical activity was virtually unimpaired. Assuming a single locus of narcotic action in the myenteric plexus, it is unlikely, therefore, that the primary action of opiates is to stimulate release of an inhibitory transmitter, to prevent release of an excitatory transmitter or to block the postsynaptic receptor for an excitatory transmitter. Rather, opiates may raise the membrane threshold of a class of neurons. Electric field stimulation activates myenteric neurons, resulting in a morphine-sensitive release of acetylcholine and a contraction of the longitudinal muscle. The ability of field stimulation to induce contractions and of morphine to inhibit these contractions, was virtually unchanged when the only two known excitatory inputs to the cholinergic motor neuron were eliminated by receptor blockade. These observations, taken together, suggest that opiates act directly on the cholinergic motor neuron of the myenteric plexus."} {"id": "PMID:173833", "title": "Effects of external ions on the synaptic transmission from photorecptors to horizontal cells in the carp retina.", "content": "1. Intracellular recordings were made from cones and horizontal cells of the isolated carp retina and the mechanisms of synaptic transmission from cones of horizontal cells were studied by changing the ionic composition of the external medium. 2. Cones were depolarized and their light responses enhanced in low Ca high-Mg medium. In the same medium, in which chemical transmission is suposed to be blocked, horizontal cells were hyperpolarized and their light responses disappeared. 3. When the synaptic input was removed, the membrane potential of horizontal cells agreed well with Ek. 4. In Na-free medium both cones and horizontal cells were hyperpolarized and response disappeared. On reaplication of normal Ringer, horizontal cells showed a trenaient membrane potential reversal (inside positive), indicating that the horizontal cell has a high Na permeability under the influence of the endogenous transmitter. 5. Application of La produced little change in cones, while it strongly depolarized horizontal cells...", "contents": "Effects of external ions on the synaptic transmission from photorecptors to horizontal cells in the carp retina. 1. Intracellular recordings were made from cones and horizontal cells of the isolated carp retina and the mechanisms of synaptic transmission from cones of horizontal cells were studied by changing the ionic composition of the external medium. 2. Cones were depolarized and their light responses enhanced in low Ca high-Mg medium. In the same medium, in which chemical transmission is suposed to be blocked, horizontal cells were hyperpolarized and their light responses disappeared. 3. When the synaptic input was removed, the membrane potential of horizontal cells agreed well with Ek. 4. In Na-free medium both cones and horizontal cells were hyperpolarized and response disappeared. On reaplication of normal Ringer, horizontal cells showed a trenaient membrane potential reversal (inside positive), indicating that the horizontal cell has a high Na permeability under the influence of the endogenous transmitter. 5. Application of La produced little change in cones, while it strongly depolarized horizontal cells..."} {"id": "PMID:173836", "title": "Neurotrophic regulation of dynamic properties of skeletal muscle: effects of botulinum toxin and denervation.", "content": "In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of dynamic properties of muscle, the effects of botulinum toxin treatment were compared with those of denervation. The extensor digitorum longus (EDL) and soleus muscles of rats were either denervated or injected with botulinum toxin. At times up to 25 days the isometric properties of these muscles were determined. 2. Both botulinum treatment and denervation produced progressive slowing of the time to peak of the twitch (TPT) and half-relaxation time of the twitch (1/2 RT), which was more pronounced in the EDL than in the soleus. 3. Both treatments produced slowing of the relaxation curve following tetanic contraction, more marked in the EDL than in the soleus muscle. This indicates a slowing of relaxation, and suggests a prolongation of the active state of the muscle. 4. The maximum rate of rise of the tetanus did not change significantly in the EDL and soleus muscles after botulinum treatment or denervation. This suggests that there is no major change in the speed of contraction under conditions of botulinum treatment or denervation. 5. The changes produced by botulinum treatment and denervation were virtually identical in all parameters tested. This is interpreted meaning that cholinergic transmission (including muscle usage), or some other factor closely related to cholinergic transmission, accounts for the motor nerve's trophic influence in maintaining these dynamic properties of skeletal muscles.", "contents": "Neurotrophic regulation of dynamic properties of skeletal muscle: effects of botulinum toxin and denervation. In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of dynamic properties of muscle, the effects of botulinum toxin treatment were compared with those of denervation. The extensor digitorum longus (EDL) and soleus muscles of rats were either denervated or injected with botulinum toxin. At times up to 25 days the isometric properties of these muscles were determined. 2. Both botulinum treatment and denervation produced progressive slowing of the time to peak of the twitch (TPT) and half-relaxation time of the twitch (1/2 RT), which was more pronounced in the EDL than in the soleus. 3. Both treatments produced slowing of the relaxation curve following tetanic contraction, more marked in the EDL than in the soleus muscle. This indicates a slowing of relaxation, and suggests a prolongation of the active state of the muscle. 4. The maximum rate of rise of the tetanus did not change significantly in the EDL and soleus muscles after botulinum treatment or denervation. This suggests that there is no major change in the speed of contraction under conditions of botulinum treatment or denervation. 5. The changes produced by botulinum treatment and denervation were virtually identical in all parameters tested. This is interpreted meaning that cholinergic transmission (including muscle usage), or some other factor closely related to cholinergic transmission, accounts for the motor nerve's trophic influence in maintaining these dynamic properties of skeletal muscles."} {"id": "PMID:173837", "title": "The mechanisms of action of chloromercuribenzene-p-sulphonic acid as insulin secretagogue: fluxes of calcium, sodium and rubidium in islets exposed to mercurial and a membrane-active antagonist.", "content": "Chloromercuribenzene-p-sulphonic acid (CMBS) is known to markedly stimulate insulin release and to enhance formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and monovalent cation permeability in the pancreatic islet cells. The effects on insulin release and cyclic AMP can be inhibited with 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS). To elucidate the role of cationic fluxes in CMBS- induced insulin release, uptake of 22Na+ and 45Ca2+ as well as efflux of 86Rb+ were studied in islets exposed to 0-1 mM CMBS or 1-0 mM SITS or both. 2. The enhancing effect of CMBS on Na+ permeability, and probably also that on Rb+ permeability, was inhibited by SITS. 3. CMBS stimulated the rate of 45Ca2+ uptakes when the islets were incubated in a poly-anionic bicarbonate buffer but not when they were incubated in Tris buffer containing only Cl- as anion. In bicarbonate buffer, the enhancement of 45Ca2+ flux was observed both with the lanthanum method for measuring intracellular 45Ca2+ uptake and with a method estimating the total islet uptake. SITS had no significant effect on the CMBS-induced 45Ca2+ uptake. 4. Chromatography on Sephadex G-15 did not reveal any significant chemical interaction between 0-1 mM CMBS and 1 mM SITS. 5. The following hypothesis for the recognition of CMBS as insulin secretagogue is suggested: by increasing Na+ permeability more than K+ permeability, CMBS depolarizes the beta-cell, leading to initiation of insulin release by an ionic mechanism which may or may not involve a change in transmembrane Ca2+ fluxes. The marked intensity of the secretory response is due to the fact that CMBS also enhances cyclic AMP formation, potentiating the effect of the ionic mechanisms on the insulin discharge apparatus.", "contents": "The mechanisms of action of chloromercuribenzene-p-sulphonic acid as insulin secretagogue: fluxes of calcium, sodium and rubidium in islets exposed to mercurial and a membrane-active antagonist. Chloromercuribenzene-p-sulphonic acid (CMBS) is known to markedly stimulate insulin release and to enhance formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and monovalent cation permeability in the pancreatic islet cells. The effects on insulin release and cyclic AMP can be inhibited with 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS). To elucidate the role of cationic fluxes in CMBS- induced insulin release, uptake of 22Na+ and 45Ca2+ as well as efflux of 86Rb+ were studied in islets exposed to 0-1 mM CMBS or 1-0 mM SITS or both. 2. The enhancing effect of CMBS on Na+ permeability, and probably also that on Rb+ permeability, was inhibited by SITS. 3. CMBS stimulated the rate of 45Ca2+ uptakes when the islets were incubated in a poly-anionic bicarbonate buffer but not when they were incubated in Tris buffer containing only Cl- as anion. In bicarbonate buffer, the enhancement of 45Ca2+ flux was observed both with the lanthanum method for measuring intracellular 45Ca2+ uptake and with a method estimating the total islet uptake. SITS had no significant effect on the CMBS-induced 45Ca2+ uptake. 4. Chromatography on Sephadex G-15 did not reveal any significant chemical interaction between 0-1 mM CMBS and 1 mM SITS. 5. The following hypothesis for the recognition of CMBS as insulin secretagogue is suggested: by increasing Na+ permeability more than K+ permeability, CMBS depolarizes the beta-cell, leading to initiation of insulin release by an ionic mechanism which may or may not involve a change in transmembrane Ca2+ fluxes. The marked intensity of the secretory response is due to the fact that CMBS also enhances cyclic AMP formation, potentiating the effect of the ionic mechanisms on the insulin discharge apparatus."} {"id": "PMID:173838", "title": "[Cerebral renin-like activity in different functional conditions (author's transl)].", "content": "Using the Boucher micromethod of determining renin activity in the frontoparietal cortex, brain stem, hypothalamus, hypophysis, and epiphysis rat tissue in different functional conditions, we have observed the following: 1 In rats previously treated with an I. V., injection of 1-1.5 ml 10% NaCl, an increase of renin-like activity was found in the cerebral cortex, brain stem and hypothalamus, whereas in the grandular tissue there was a significant decrease...", "contents": "[Cerebral renin-like activity in different functional conditions (author's transl)]. Using the Boucher micromethod of determining renin activity in the frontoparietal cortex, brain stem, hypothalamus, hypophysis, and epiphysis rat tissue in different functional conditions, we have observed the following: 1 In rats previously treated with an I. V., injection of 1-1.5 ml 10% NaCl, an increase of renin-like activity was found in the cerebral cortex, brain stem and hypothalamus, whereas in the grandular tissue there was a significant decrease..."} {"id": "PMID:173845", "title": "Steroid production by the isolated rabbit ovarian follicle.", "content": "Graafian follicles from New Zealand white rabbits were incubated at 37 degrees C for various periods of time with air as the gas phase. Media were changed every 15 min and stored at -15 degrees C until analysed for progestins, 17 beta-hydroxyandrogens and oestrogens using established radioimmunoassay procedures. At fixed times after the start of the incubations, media containing various test substances were added with subsequent replacement by medium alone. Addition of 5 mug LH/ml for 1 sec caused a dramatic increase in the synthesis and secretion of androgen with lesser increases in progestin and oestrogen. Puromycin and cycloheximide but not actinomycin D, inhibited LH-induced steroidogenesis. Cycli AMP, dibutyryl cycli AMP, cyclic CMP, 5'-AMP, and theophylline also caused an increase in androgen production which rapidly ceased when media without nucleotides were added. Sodium fluoride had no effect on steroidogenesis. From these data it was concluded that (i) the rabbit follicle is the major source of ovarian androgen; (ii) the binding of LH to the follicular cells is a rapid process; (iii) the events following LH binding do not require the presence of LH in the medium; (iv) cyclic nucleotides which may act as second messengers also stimulate steroidogenesis; (v) the effects of LH and cyclic nucleotides on steroidogenesis are different; and (vi) the action of LH on follicular steroidogenesis probably occurs in the translational level.", "contents": "Steroid production by the isolated rabbit ovarian follicle. Graafian follicles from New Zealand white rabbits were incubated at 37 degrees C for various periods of time with air as the gas phase. Media were changed every 15 min and stored at -15 degrees C until analysed for progestins, 17 beta-hydroxyandrogens and oestrogens using established radioimmunoassay procedures. At fixed times after the start of the incubations, media containing various test substances were added with subsequent replacement by medium alone. Addition of 5 mug LH/ml for 1 sec caused a dramatic increase in the synthesis and secretion of androgen with lesser increases in progestin and oestrogen. Puromycin and cycloheximide but not actinomycin D, inhibited LH-induced steroidogenesis. Cycli AMP, dibutyryl cycli AMP, cyclic CMP, 5'-AMP, and theophylline also caused an increase in androgen production which rapidly ceased when media without nucleotides were added. Sodium fluoride had no effect on steroidogenesis. From these data it was concluded that (i) the rabbit follicle is the major source of ovarian androgen; (ii) the binding of LH to the follicular cells is a rapid process; (iii) the events following LH binding do not require the presence of LH in the medium; (iv) cyclic nucleotides which may act as second messengers also stimulate steroidogenesis; (v) the effects of LH and cyclic nucleotides on steroidogenesis are different; and (vi) the action of LH on follicular steroidogenesis probably occurs in the translational level."} {"id": "PMID:173846", "title": "The sheep ovary: regulation of steroidogenic, haemodynamic and structural changes in the largest follicle and adjacent tissue before ovulation.", "content": "Important changes occur in the follicle that is destined to ovulate and also in the surrounding ovarian tissue of sheep during the 72 hr preceding ovulation. It is our purpose to describe the morphological and functional changes that take place in large follicles during the preovulatory period and to relate these to the local ovarian environment and general endocrine status prevailing at this time. A consideration of changes in the structure, blood supply and function of the ovaries in vivo, is followed by a discussion of the functional capacity of the individual ovarian components when isolated and studied in vitro. Against this background, the nature and sequence of events that occur in the preovulatory follicle and the mechanisms which regulate them will be discussed.", "contents": "The sheep ovary: regulation of steroidogenic, haemodynamic and structural changes in the largest follicle and adjacent tissue before ovulation. Important changes occur in the follicle that is destined to ovulate and also in the surrounding ovarian tissue of sheep during the 72 hr preceding ovulation. It is our purpose to describe the morphological and functional changes that take place in large follicles during the preovulatory period and to relate these to the local ovarian environment and general endocrine status prevailing at this time. A consideration of changes in the structure, blood supply and function of the ovaries in vivo, is followed by a discussion of the functional capacity of the individual ovarian components when isolated and studied in vitro. Against this background, the nature and sequence of events that occur in the preovulatory follicle and the mechanisms which regulate them will be discussed."} {"id": "PMID:173847", "title": "Coital exanthema in stallions.", "content": "Equine coital exanthema can be produced experimentally in stallions by inoculation with an equine herpesvirus (strain 65/61) and be transmitted during coitus with an infected mare. Serological responses to this infection include the production of complement-fixing and serum-neutralizing antibodies which reach maximum levels 14 to 21 days after infection. Complement-fixing antibodies decline rapidly and are usually not detectable by 60 days after infection, whereas serum-neutralizing antibody activity is maintained for at least 1 year. This disparity provides a useful method for the diagnosis of recent infections and estimation of the temporal incidence of infection in groups of mares. It seems likely that clinically normal carrier mares spread the virus on studs where the disease has previously not occurred.", "contents": "Coital exanthema in stallions. Equine coital exanthema can be produced experimentally in stallions by inoculation with an equine herpesvirus (strain 65/61) and be transmitted during coitus with an infected mare. Serological responses to this infection include the production of complement-fixing and serum-neutralizing antibodies which reach maximum levels 14 to 21 days after infection. Complement-fixing antibodies decline rapidly and are usually not detectable by 60 days after infection, whereas serum-neutralizing antibody activity is maintained for at least 1 year. This disparity provides a useful method for the diagnosis of recent infections and estimation of the temporal incidence of infection in groups of mares. It seems likely that clinically normal carrier mares spread the virus on studs where the disease has previously not occurred."} {"id": "PMID:173848", "title": "Morphology and histochemistry of the endometrial cup.", "content": "The luminal and cut surface of endometrial cups were examined by scanning electron microscopy. The distribution of PAS-positive and lipid materials in cup tissue was studied and most of the lipid material was localized in the large polyhedral cup cells. The lipid droplets gave positive reactions for DNPH in the cholesterol test of Schultz. They also exhibited autofluorescence and were therefore considered to be steroidal in nature. The significance of this possibility, particularly with regard to maintenance of early pregnancy in the mare, is discussed.", "contents": "Morphology and histochemistry of the endometrial cup. The luminal and cut surface of endometrial cups were examined by scanning electron microscopy. The distribution of PAS-positive and lipid materials in cup tissue was studied and most of the lipid material was localized in the large polyhedral cup cells. The lipid droplets gave positive reactions for DNPH in the cholesterol test of Schultz. They also exhibited autofluorescence and were therefore considered to be steroidal in nature. The significance of this possibility, particularly with regard to maintenance of early pregnancy in the mare, is discussed."} {"id": "PMID:173849", "title": "Experimental studies on equine herpesvirus type 1 infections.", "content": "The EHV-1 viruses of fetal origin grew better and had a wider tissue culture host range than those isolated from horses with respiratory diseases. Comparisons of a fetal isolate (F/304) and a respiratory disease isolate (R/NM-3) in partly immune horses showed that the F/304 virus infected horses more readily, grew better in the nasopharynx, was more likely to cause abortion, and was excreted to a greater extent into the environment.", "contents": "Experimental studies on equine herpesvirus type 1 infections. The EHV-1 viruses of fetal origin grew better and had a wider tissue culture host range than those isolated from horses with respiratory diseases. Comparisons of a fetal isolate (F/304) and a respiratory disease isolate (R/NM-3) in partly immune horses showed that the F/304 virus infected horses more readily, grew better in the nasopharynx, was more likely to cause abortion, and was excreted to a greater extent into the environment."} {"id": "PMID:173851", "title": "Specificity in enzyme inhibition. 3. Synthesis of 5-substituted 2,2-dimethyl-4-imidazolidinones as inhibitors of tyrosine decarboxylase and histidine decarboxylase.", "content": "2,2-Dimethyl-4-imidazolidinone derivatives of the alpha-amino acids DL-phenylglycine (1), DL-phenylalanine (2), L-tyrosine (3), L-histidine (4), and L-tryptophan (5) were prepared in order to assess their specificity in inhibiting amino acid decarboxylases. Treatment of th alpha-aminonitriles with acetone in the presence of base and heat or treatment of the alpha-amino amides with acetone gave the title compounds in 48-85% yield. The compounds afforded moderate ability to inhibit the decarboxylation of L-phenylalanine, L-tyrosine, or L-histidine in vitro, using crude enzymes. 3 was a better inhibitor of tyrosine decarboxylase (S. faecalis) than 2. 4 and 5 were comparable to 3 in inhibiting tyrosine decarboxylase. 4 was more selective in inhibiting purified histidine decarboxylase (Cl. welchii) than 5, which was inactive. 4 was inactive against fetal rat histidine decarboxylase in vitro.", "contents": "Specificity in enzyme inhibition. 3. Synthesis of 5-substituted 2,2-dimethyl-4-imidazolidinones as inhibitors of tyrosine decarboxylase and histidine decarboxylase. 2,2-Dimethyl-4-imidazolidinone derivatives of the alpha-amino acids DL-phenylglycine (1), DL-phenylalanine (2), L-tyrosine (3), L-histidine (4), and L-tryptophan (5) were prepared in order to assess their specificity in inhibiting amino acid decarboxylases. Treatment of th alpha-aminonitriles with acetone in the presence of base and heat or treatment of the alpha-amino amides with acetone gave the title compounds in 48-85% yield. The compounds afforded moderate ability to inhibit the decarboxylation of L-phenylalanine, L-tyrosine, or L-histidine in vitro, using crude enzymes. 3 was a better inhibitor of tyrosine decarboxylase (S. faecalis) than 2. 4 and 5 were comparable to 3 in inhibiting tyrosine decarboxylase. 4 was more selective in inhibiting purified histidine decarboxylase (Cl. welchii) than 5, which was inactive. 4 was inactive against fetal rat histidine decarboxylase in vitro."} {"id": "PMID:173858", "title": "Deviations from compositional randomness in eukaryotic and prokaryotic proteins: the hypothesis of selective-stochastic stability and a principle of charge conservation.", "content": "Eight proteins of diverse lengths, functions, and origin, are examined for compositional non-randomness amino acid by amino acid. The proteins investigated are human fibrinopeptide A, guinea pig Insulin, rattlesnake cytochrome c, MS2 phage coat protein, rabbit triosephosphate isomerase, bovine pancreatic deoxyribonuclease A, bovine glutamate dehydrogenase, and Bacillus thermoproteolyticus thermolysin. As a result of this study the experimentally testable hypothesis is put forth that for a large class of proteins the ratio of that fraction of the molecule which exhibits compositional non-randomness to that fraction which does not is on the average, stable about a mean value (estimated as 0.32 plus or minus 0.17) and (nearly) independent of protein length. Stochastic and selective evolutionary forces are viewed as interacting rather than independent phenomena. With respect to amino acid composition, this coupling ameliorates the current controversy over Darwinian vs. non-Darwinian evolution, selectionist vs. neutralist, in favor of neither: Within the context of the quantitative data, the evolution of real proteins is seen as a compromise between the two viewpoints, both important. The compositional fluctuations of the electrically charged amino acids glutamic and aspartic acid, lysine and arginine, are examined in depth for over eighty protein families, both prokaryotic and eukaryotic. For both taxa, each of the acidic amino acids is present in amounts roughly twice that predicted from the genetic code. The presence of an excess of glutamic acid is independent of the presence of an excess of aspartic acid and vice versa.", "contents": "Deviations from compositional randomness in eukaryotic and prokaryotic proteins: the hypothesis of selective-stochastic stability and a principle of charge conservation. Eight proteins of diverse lengths, functions, and origin, are examined for compositional non-randomness amino acid by amino acid. The proteins investigated are human fibrinopeptide A, guinea pig Insulin, rattlesnake cytochrome c, MS2 phage coat protein, rabbit triosephosphate isomerase, bovine pancreatic deoxyribonuclease A, bovine glutamate dehydrogenase, and Bacillus thermoproteolyticus thermolysin. As a result of this study the experimentally testable hypothesis is put forth that for a large class of proteins the ratio of that fraction of the molecule which exhibits compositional non-randomness to that fraction which does not is on the average, stable about a mean value (estimated as 0.32 plus or minus 0.17) and (nearly) independent of protein length. Stochastic and selective evolutionary forces are viewed as interacting rather than independent phenomena. With respect to amino acid composition, this coupling ameliorates the current controversy over Darwinian vs. non-Darwinian evolution, selectionist vs. neutralist, in favor of neither: Within the context of the quantitative data, the evolution of real proteins is seen as a compromise between the two viewpoints, both important. The compositional fluctuations of the electrically charged amino acids glutamic and aspartic acid, lysine and arginine, are examined in depth for over eighty protein families, both prokaryotic and eukaryotic. For both taxa, each of the acidic amino acids is present in amounts roughly twice that predicted from the genetic code. The presence of an excess of glutamic acid is independent of the presence of an excess of aspartic acid and vice versa."} {"id": "PMID:173860", "title": "Influence of riboflavin on disturbances in trytophan metabolism and hepatoma production after a single dose of aflatoxin B1.", "content": "Female Wistar rats were given a single oral dose of aflatoxin B1, either alone or with a large amount of riboflavin. Biochemical and histologic studies were performed for 30 months. Nine animals of 19 in the aflatoxin-treated group and only 5 of 18 in the riboflavin-aflatoxin-treated group developed hepatomas. The number of rats was insufficient for tests of statistical significance to be fruitful. Urinary excretion of tryptophan metabolites was studied in aflatoxin- and riboflavin-treated rats after an oral administration of 10 mg tryptophan/100 g rat. Riboflavin did not affect the percentage of aflatoxin-treated animals with abnormal urinary excretion patterns, but did increase the magnitude of the disturbances in elimination of kynurenic and xanthurenic acids. The hepatic tryptophan-oxygenase activity was increased only in the two groups given riboflavin, and the levels of nucleic acids were the same in all groups.", "contents": "Influence of riboflavin on disturbances in trytophan metabolism and hepatoma production after a single dose of aflatoxin B1. Female Wistar rats were given a single oral dose of aflatoxin B1, either alone or with a large amount of riboflavin. Biochemical and histologic studies were performed for 30 months. Nine animals of 19 in the aflatoxin-treated group and only 5 of 18 in the riboflavin-aflatoxin-treated group developed hepatomas. The number of rats was insufficient for tests of statistical significance to be fruitful. Urinary excretion of tryptophan metabolites was studied in aflatoxin- and riboflavin-treated rats after an oral administration of 10 mg tryptophan/100 g rat. Riboflavin did not affect the percentage of aflatoxin-treated animals with abnormal urinary excretion patterns, but did increase the magnitude of the disturbances in elimination of kynurenic and xanthurenic acids. The hepatic tryptophan-oxygenase activity was increased only in the two groups given riboflavin, and the levels of nucleic acids were the same in all groups."} {"id": "PMID:173861", "title": "Cell populations and known surface antigens of tumors induced by Abelson virus in pristane-primed BALB/c mice: an analysis by immunoelectron microscopy;.", "content": "When Abelson murine leukemia virus (MuLV-A) was inoculated into pristane-primed BALB/c mice, either plasmacytomas (PCT), lymphosarcomas, or their mixed form was induced with a shorter latent period than that for PCT induction in mice treated with pristane alone. All 3 neoplasms were designated Abelson's tumors. The morphology of the induced malignant cells and the presence of known surface antigens were analyzed by electron microscopy. The cell surface antigens (CSA) examined were PC1, X.1, Gross (GCSA), and Moloney (MCSA); viral envelope antigens (VEA) were xVEA, x1-VEA, sub-gsVEA, and MVEA. MuLV-A-pristane-induced PCT cells produced markedly fewer intracisternal type-A particles than did mineral oil-induced PCT cells. Most, if not all, mineral oil-induced PCT cells carried PC1 antigen and produced many extracellular type-C viruses carrying xVEA and x1-VEA, whereas Abelson's tumor cells had both a lower incidence and a smaller amount of PC1 and X.1 antigens and xVEA+ virus and lacked x1-VEA+ virus. In addition, most Abelson's tumors and their type-C viruses did not carry MCSA and MVEA ro GCSA and sub-gsVEA. All the macrophages in the PC1+ Abelson's tumors and many macrophages in PC1-Abelson's tumors contained various amounts of PC1 on their cell surfaces. For these reasons, Abelson's tumors were clearly distinct from pristane- or mineral oil-induced BALB/c PCT and from M-MuLV- ro G-MuLV-induced tumors.", "contents": "Cell populations and known surface antigens of tumors induced by Abelson virus in pristane-primed BALB/c mice: an analysis by immunoelectron microscopy;. When Abelson murine leukemia virus (MuLV-A) was inoculated into pristane-primed BALB/c mice, either plasmacytomas (PCT), lymphosarcomas, or their mixed form was induced with a shorter latent period than that for PCT induction in mice treated with pristane alone. All 3 neoplasms were designated Abelson's tumors. The morphology of the induced malignant cells and the presence of known surface antigens were analyzed by electron microscopy. The cell surface antigens (CSA) examined were PC1, X.1, Gross (GCSA), and Moloney (MCSA); viral envelope antigens (VEA) were xVEA, x1-VEA, sub-gsVEA, and MVEA. MuLV-A-pristane-induced PCT cells produced markedly fewer intracisternal type-A particles than did mineral oil-induced PCT cells. Most, if not all, mineral oil-induced PCT cells carried PC1 antigen and produced many extracellular type-C viruses carrying xVEA and x1-VEA, whereas Abelson's tumor cells had both a lower incidence and a smaller amount of PC1 and X.1 antigens and xVEA+ virus and lacked x1-VEA+ virus. In addition, most Abelson's tumors and their type-C viruses did not carry MCSA and MVEA ro GCSA and sub-gsVEA. All the macrophages in the PC1+ Abelson's tumors and many macrophages in PC1-Abelson's tumors contained various amounts of PC1 on their cell surfaces. For these reasons, Abelson's tumors were clearly distinct from pristane- or mineral oil-induced BALB/c PCT and from M-MuLV- ro G-MuLV-induced tumors."} {"id": "PMID:173862", "title": "Response of C3H-AvyfB female mice to a low oncogenic, milk-borne mammary tumor virus.", "content": "When low oncogenic milk-borne mammary tumor virus (MTV) of strain DD was tested in C3H-AvyfB mice, as compared with the similar strain C3HfB, mammary tumors occurred with a higher incidence and at lower age in C3H-AvyfBfDD (with DD-MTV) than in C3HfBfDD (with DD-MTV), as observed in virgin females. Since the effect of breeding tended to mask any difference between the breeders, mammary tumor incidences were similar with a slightly higher age at tumor occurrence in the C3H-AvyfBfDD females. Thus the C3H-AvyfB virgins (with the Avy gene) were almost as susceptible to mammary tumors with the less potent DD-MTV as were C3HfB virgins with the more virulent C3H-MTV of strain C3H.", "contents": "Response of C3H-AvyfB female mice to a low oncogenic, milk-borne mammary tumor virus. When low oncogenic milk-borne mammary tumor virus (MTV) of strain DD was tested in C3H-AvyfB mice, as compared with the similar strain C3HfB, mammary tumors occurred with a higher incidence and at lower age in C3H-AvyfBfDD (with DD-MTV) than in C3HfBfDD (with DD-MTV), as observed in virgin females. Since the effect of breeding tended to mask any difference between the breeders, mammary tumor incidences were similar with a slightly higher age at tumor occurrence in the C3H-AvyfBfDD females. Thus the C3H-AvyfB virgins (with the Avy gene) were almost as susceptible to mammary tumors with the less potent DD-MTV as were C3HfB virgins with the more virulent C3H-MTV of strain C3H."} {"id": "PMID:173863", "title": "Type-C RNA viruses of the NIH nude mouse.", "content": "Several types of tumors from various species were propagated in NIH athymic nude mice. Subsequently, cell lines were established from the tumors and examined for evidence of type-C virus activity. Hybrid mice (NIH Swiss and BALB/c) harbored murine type-C viruses of three categories: N-tropic, B-tropic and X-tropic.", "contents": "Type-C RNA viruses of the NIH nude mouse. Several types of tumors from various species were propagated in NIH athymic nude mice. Subsequently, cell lines were established from the tumors and examined for evidence of type-C virus activity. Hybrid mice (NIH Swiss and BALB/c) harbored murine type-C viruses of three categories: N-tropic, B-tropic and X-tropic."} {"id": "PMID:173864", "title": "Attenuation of herpesvirus saimiri for marmosets after successive passage in cell culture at 39 degrees C.", "content": "A variant of Herpesvirus saimiri (HVS) stably attenuated for marmosets was isolated after serial passage of wild-type HVS in cell culture at 39 degrees C. Marmosets previously inoculated with attenuated virus experienced a significant delay in the development of lymphoma when challenged with wild-type HVS.", "contents": "Attenuation of herpesvirus saimiri for marmosets after successive passage in cell culture at 39 degrees C. A variant of Herpesvirus saimiri (HVS) stably attenuated for marmosets was isolated after serial passage of wild-type HVS in cell culture at 39 degrees C. Marmosets previously inoculated with attenuated virus experienced a significant delay in the development of lymphoma when challenged with wild-type HVS."} {"id": "PMID:173865", "title": "Tumor regression caused by endotoxins and mycobacterial fractions.", "content": "A transplantable hepatocarcinoma of guinea pigs was used as an experimental model for immunotherapy of cancer. Earlier work showed that complete regression of 6- to 7-day-old tumors could be obtained in about 60% of cases by inoculation of the tumors with live BCG or certain fractions of BCG attached to minute oil droplets and suspended in Tween-saline. One of the most essential fractions was P3, a nonsensitizing, nonantigenic trehalose mycolate related to, but not identical with, cord factor. We now report that oil-droplet preparations containing P3 and bacterial endotoxin (ET) produced cure rates of up to 90% in the same system. In addition, regression was faster than with BCG, and older tumors could be treated successfully. The most effective ET's were from rough strains of salmonellae, known as Re mutants, which could not synthesize and attach the polysaccharide portion of endotoxin.", "contents": "Tumor regression caused by endotoxins and mycobacterial fractions. A transplantable hepatocarcinoma of guinea pigs was used as an experimental model for immunotherapy of cancer. Earlier work showed that complete regression of 6- to 7-day-old tumors could be obtained in about 60% of cases by inoculation of the tumors with live BCG or certain fractions of BCG attached to minute oil droplets and suspended in Tween-saline. One of the most essential fractions was P3, a nonsensitizing, nonantigenic trehalose mycolate related to, but not identical with, cord factor. We now report that oil-droplet preparations containing P3 and bacterial endotoxin (ET) produced cure rates of up to 90% in the same system. In addition, regression was faster than with BCG, and older tumors could be treated successfully. The most effective ET's were from rough strains of salmonellae, known as Re mutants, which could not synthesize and attach the polysaccharide portion of endotoxin."} {"id": "PMID:173866", "title": "Quantitative cloning of malignant human glioma cells by conditioned medium.", "content": "The use of conditioned medium (CM) obtained from monolayer cultures of human glioma cells induced colony formation from single glioma cells in culture. In contrast, no colonies were observed in cultures incubated with nonconditioned standard Eagle's basal medium. The number of colonies formed closely depended on the concentration of CM. The glioma CM not only stimulated colony formation but also induced the formation of fibrillary cell extensions. Culture conditions influencing the production of colony-stimulating factors included cell density and duration of culture medium contact with glioma cells. The colony-stimulating activity (CSA) was stable after freezing and thawing, but decreased 30-40% when CM was exposed to temperatures over 66 degrees C for 30 minutes. In addition, the CSA was filtratable (0.45 mu), dialyzable, and passable through an Amicon PM10 filter, which indicated a molecular weight less than 10,000. The use of CM provided an improved method for quantitative assays of neural tumor cells, based on their colony formation in culture.", "contents": "Quantitative cloning of malignant human glioma cells by conditioned medium. The use of conditioned medium (CM) obtained from monolayer cultures of human glioma cells induced colony formation from single glioma cells in culture. In contrast, no colonies were observed in cultures incubated with nonconditioned standard Eagle's basal medium. The number of colonies formed closely depended on the concentration of CM. The glioma CM not only stimulated colony formation but also induced the formation of fibrillary cell extensions. Culture conditions influencing the production of colony-stimulating factors included cell density and duration of culture medium contact with glioma cells. The colony-stimulating activity (CSA) was stable after freezing and thawing, but decreased 30-40% when CM was exposed to temperatures over 66 degrees C for 30 minutes. In addition, the CSA was filtratable (0.45 mu), dialyzable, and passable through an Amicon PM10 filter, which indicated a molecular weight less than 10,000. The use of CM provided an improved method for quantitative assays of neural tumor cells, based on their colony formation in culture."} {"id": "PMID:173867", "title": "In vitro evaluation of cell-mediated immunity to Epstein-Barr herpesvirus by cell migration inhibition tests.", "content": "Migration of peripheral leukocytes in samples from sensitized [Epstein-Barr virus (EBV) antibody-positive] humans was greatly inhibited when challenged by antigen prepared from EBV-producing P3HR-1 cells but not by antigen prepared from EBV-nonproducing RAJI cells, EBV-negative human fibroblasts, or epithelial cells. Such inhibition was not observed when peripheral leuocytes from subjects or neonates not sensitized to EBV were challenged. Similar results were obtained in a two-stage test when the same leukocyte samples were challenged in vitro by antigen prepared from P3HR-1 cells and the cell-free supernatant was assayed for migration inhibition factor (MIF) in the guinea pig macrophage migration inhibition test; migration of guinea pig peritoneal exudate cells was greatly inhibited by the supernatant filtrates of leukocyte cultures only from subjects positive for EBV-antibody. Furthermore, this inhibitory effect was not observed if supernatant filtrates from leukocyte cultures challenged by antigens prepared from RAJI cells, fibroblasts, or epithelial cells were used. The EBV antigen transformed peripheral leukocytes and induced early antigen production in RAJI cells; however, a \"killed\" preparation (by UV irradiation) was sufficient for eliciting MIF production.", "contents": "In vitro evaluation of cell-mediated immunity to Epstein-Barr herpesvirus by cell migration inhibition tests. Migration of peripheral leukocytes in samples from sensitized [Epstein-Barr virus (EBV) antibody-positive] humans was greatly inhibited when challenged by antigen prepared from EBV-producing P3HR-1 cells but not by antigen prepared from EBV-nonproducing RAJI cells, EBV-negative human fibroblasts, or epithelial cells. Such inhibition was not observed when peripheral leuocytes from subjects or neonates not sensitized to EBV were challenged. Similar results were obtained in a two-stage test when the same leukocyte samples were challenged in vitro by antigen prepared from P3HR-1 cells and the cell-free supernatant was assayed for migration inhibition factor (MIF) in the guinea pig macrophage migration inhibition test; migration of guinea pig peritoneal exudate cells was greatly inhibited by the supernatant filtrates of leukocyte cultures only from subjects positive for EBV-antibody. Furthermore, this inhibitory effect was not observed if supernatant filtrates from leukocyte cultures challenged by antigens prepared from RAJI cells, fibroblasts, or epithelial cells were used. The EBV antigen transformed peripheral leukocytes and induced early antigen production in RAJI cells; however, a \"killed\" preparation (by UV irradiation) was sufficient for eliciting MIF production."} {"id": "PMID:173868", "title": "Natural and experimentally induced antibodies to defined mammalian type-C virus proteins in primates.", "content": "Using sensitive radiommunoprecipitation assays for highly purified type-C RNA tumor virus proteins, we found that 5 of 16 clinically normal gibbons (including 4 of 5 normal animals from a colony with 2 cases of lymphoma) and 4 of 4 experimentally inoculated gibbons formed antibodies to the major structural protein (p30) of gibbon ape leukemia virus (GaLV). An additional woolly monkey immunized with the closely related simian sarcoma virus also formed antibodies detectable with GaLV p30. Of 20 patients immunized with formalin-inactivated Rauscher murine leukemia virus (R-MuLV), 10 were previously reported to have antibodies to MuLV as determined by an internally labeled banded virus radioimmunoprecipitation assay. In comparison studies with purified R-MuLV proteins, 7 of 20 patients formed antibodies: 3/20 to R-MuLV p30 only, 1/20 to R-MuLV glycoprotein (gp) 70 only, and 3/20 to both p30 and gp70. Most responders were melanoma patients receiving immunotherapy with BCG. Additionally, rhesus monkeys produced antibodies to the endogenous cat virus RD114 and closely related endogenous baboon leukemia virus p30's. Thus these studies demonstrated the ability of primates (including humans) to form antibodies to well-characterized proteins from endogenous and exogenous type-C viruses and the potential utility of these assays for seroepidemiologic studies.", "contents": "Natural and experimentally induced antibodies to defined mammalian type-C virus proteins in primates. Using sensitive radiommunoprecipitation assays for highly purified type-C RNA tumor virus proteins, we found that 5 of 16 clinically normal gibbons (including 4 of 5 normal animals from a colony with 2 cases of lymphoma) and 4 of 4 experimentally inoculated gibbons formed antibodies to the major structural protein (p30) of gibbon ape leukemia virus (GaLV). An additional woolly monkey immunized with the closely related simian sarcoma virus also formed antibodies detectable with GaLV p30. Of 20 patients immunized with formalin-inactivated Rauscher murine leukemia virus (R-MuLV), 10 were previously reported to have antibodies to MuLV as determined by an internally labeled banded virus radioimmunoprecipitation assay. In comparison studies with purified R-MuLV proteins, 7 of 20 patients formed antibodies: 3/20 to R-MuLV p30 only, 1/20 to R-MuLV glycoprotein (gp) 70 only, and 3/20 to both p30 and gp70. Most responders were melanoma patients receiving immunotherapy with BCG. Additionally, rhesus monkeys produced antibodies to the endogenous cat virus RD114 and closely related endogenous baboon leukemia virus p30's. Thus these studies demonstrated the ability of primates (including humans) to form antibodies to well-characterized proteins from endogenous and exogenous type-C viruses and the potential utility of these assays for seroepidemiologic studies."} {"id": "PMID:173869", "title": "Induction of liver tumor in Sherman strain female rats by polychlorinated biphenyl aroclor 1260.", "content": "Sherman strain female rats (200) were fed 100 ppm of polychlorinated biphenyl (Aroclor 1260) for apporximately 21 months, and 200 female rats were kept as controls. The rats were killed when 23 months old. Twenty-six of 184 experimental animals and 1 of 173 controls had hepatocellular carcinomas. None of the controls but 146 of 184 experimental rats had neoplastic nodules in their livers, and areas of hepatocellular alteration were noted in 28 of 173 controls and 182 of 184 experimental animals. Thus the polychlorinated biphenyl Aroclor 1260, when fed in the diet, had a hepatocarcinogenic effect in these rats. The incidence of tumors in other organs did not differ appreciably between the experimental and control groups.", "contents": "Induction of liver tumor in Sherman strain female rats by polychlorinated biphenyl aroclor 1260. Sherman strain female rats (200) were fed 100 ppm of polychlorinated biphenyl (Aroclor 1260) for apporximately 21 months, and 200 female rats were kept as controls. The rats were killed when 23 months old. Twenty-six of 184 experimental animals and 1 of 173 controls had hepatocellular carcinomas. None of the controls but 146 of 184 experimental rats had neoplastic nodules in their livers, and areas of hepatocellular alteration were noted in 28 of 173 controls and 182 of 184 experimental animals. Thus the polychlorinated biphenyl Aroclor 1260, when fed in the diet, had a hepatocarcinogenic effect in these rats. The incidence of tumors in other organs did not differ appreciably between the experimental and control groups."} {"id": "PMID:173870", "title": "Intracisternal A and C particles in mouse neurons: a thin-section study of normal trigeminal ganglion and C1300 neuroblastoma.", "content": "Trigerminal ganglia of 4 adult albino mice of the NMRI outbred stock were examined by electron microscopy. In all animals, about 10% of the neurons contained intracisternal A particles. Isolated structures resembling intracisternal A particles could be detected in atleast 50% of the nerve cells and in a few Schwann cells. Budding at the cell surface and/or extracellular type-C particles were not observed. An intracerebrally transplanted mouse C1300 neuroblastoma was likewise studied. Most tumor cells exhibited large numbers of intracisternal A particles having the same ultrastructure as the particles in trigeminal neurons. In addition, budding and extracellular type-C particles were occasionally observed.", "contents": "Intracisternal A and C particles in mouse neurons: a thin-section study of normal trigeminal ganglion and C1300 neuroblastoma. Trigerminal ganglia of 4 adult albino mice of the NMRI outbred stock were examined by electron microscopy. In all animals, about 10% of the neurons contained intracisternal A particles. Isolated structures resembling intracisternal A particles could be detected in atleast 50% of the nerve cells and in a few Schwann cells. Budding at the cell surface and/or extracellular type-C particles were not observed. An intracerebrally transplanted mouse C1300 neuroblastoma was likewise studied. Most tumor cells exhibited large numbers of intracisternal A particles having the same ultrastructure as the particles in trigeminal neurons. In addition, budding and extracellular type-C particles were occasionally observed."} {"id": "PMID:173871", "title": "Post-traumatic blood lipid changes and fat embolism. Relation of post-traumatic blood lipid changes and fat embolism syndrome.", "content": "Serum cholesterol, triglycerides, phospholipids, and lipoprotein levels were studied by electrophoresis in 43 trauma patients with multiple fractures of the lower extremities and pelvis. Ten healthy volunteers were used for control studies. The fat embolism syndrome was diagnosed in eight of the 43 patients. The lipid values of all the trauma patients were lower than the control values. A decrease in cholesterol and phospholipids was observed in the fat embolism patients during 4 days; these changes were not observed in the other trauma patients. The triglycerides of all the trauma patients increased slowly over a period of 4 days. Changes in the lipoprotein fractions after the trauma were minor. An early increase in the alpha1 lipbrotein fraction was noted in the fat embolism patients simultaneously with a decrease in the pre-beta lipoprotein fraction; the values of the other trauma patients were at the control levels. Normalization was observed in 6 hours. The lipid concentrations of plasma and serum did not change with filtration with 1.2, 5, and 8mum Millipore filters. No differences were noted between the femoral and cubital vein samples.", "contents": "Post-traumatic blood lipid changes and fat embolism. Relation of post-traumatic blood lipid changes and fat embolism syndrome. Serum cholesterol, triglycerides, phospholipids, and lipoprotein levels were studied by electrophoresis in 43 trauma patients with multiple fractures of the lower extremities and pelvis. Ten healthy volunteers were used for control studies. The fat embolism syndrome was diagnosed in eight of the 43 patients. The lipid values of all the trauma patients were lower than the control values. A decrease in cholesterol and phospholipids was observed in the fat embolism patients during 4 days; these changes were not observed in the other trauma patients. The triglycerides of all the trauma patients increased slowly over a period of 4 days. Changes in the lipoprotein fractions after the trauma were minor. An early increase in the alpha1 lipbrotein fraction was noted in the fat embolism patients simultaneously with a decrease in the pre-beta lipoprotein fraction; the values of the other trauma patients were at the control levels. Normalization was observed in 6 hours. The lipid concentrations of plasma and serum did not change with filtration with 1.2, 5, and 8mum Millipore filters. No differences were noted between the femoral and cubital vein samples."} {"id": "PMID:173872", "title": "The acute carpal tunnel syndrome: nine case reports.", "content": "Nine cases of acute carpal tunnel syndrome are reported. Etiologies include: bleeding secondary to chronic lymphatic leukemia; Colles' fracture of the wrist (2 cases); Epiphyseal fracture (Salter II) of the distal radius; Bleeding secondary to giant cell tumor of the tendon sheath; Unstable distal radio-ulnar joint; Displaced intra-articular fracture of the distal radius; Rheumatoid synovitis and vasculitis; Trans-scaphoid, perilunar fracture dislocation of the wrist. Early recognition of median nerve compression in the carpal tunnel is vital. The signs of median nerve compression should be looked for in all cases of wrist trauma. In our opinion, immediate surgical decompression is frequently indicated.", "contents": "The acute carpal tunnel syndrome: nine case reports. Nine cases of acute carpal tunnel syndrome are reported. Etiologies include: bleeding secondary to chronic lymphatic leukemia; Colles' fracture of the wrist (2 cases); Epiphyseal fracture (Salter II) of the distal radius; Bleeding secondary to giant cell tumor of the tendon sheath; Unstable distal radio-ulnar joint; Displaced intra-articular fracture of the distal radius; Rheumatoid synovitis and vasculitis; Trans-scaphoid, perilunar fracture dislocation of the wrist. Early recognition of median nerve compression in the carpal tunnel is vital. The signs of median nerve compression should be looked for in all cases of wrist trauma. In our opinion, immediate surgical decompression is frequently indicated."} {"id": "PMID:173875", "title": "Inhibition of cellular protein synthesis by simultaneous pretreatment of host cells with fowl plague virus and actinomycin D: a method for studying early protein synthesis of several RNA viruses.", "content": "A method is described for analysis of viral protein synthesis early after infection when minute amounts of viral proteins are effectively concealed by large amounts of produced host-specific proteins. The method is superior to a radioimmune assay, since all virus-induced proteins can be measured independent of their immunological reactivity. Host-specific protein synthesis can be suppressed by infection with fowl plague virus. Addition of actinomycin C 1.25 h postinfection does not prevent this suppression, but it does block effectively the formation of fowl plague virus-specific proteins. Such cells synthesize only small amounts of cellular proteins, as revealed by polyacrylamide electrophoresis. They can be superinfected with several different enveloped viruses, however, without significant diminution of virus yeilds. In pretreated cells the eclipse is shortened for Semliki Forest virus, Sindbis virus, and vesicular stomatitis virus, but prolonged for Newcastle disease virus. The onset of protein synthesis, specific for the superinfecting virus, could be clearly demonstrated within 1 h after superinfection. At this time, in cells superinfected with Semliki Forest virus, great amounts of NSP 75 (nonstructural protein; molecular weight, 75 X 10(3)) and reduced amounts of the core protein C could be deomonstrated. The precursor glycoprotein NSP 68 is followed by a new polypeptide, NSP 65: three proteins with molecular weights exceeding 100 X 10(3) were observed which are missing later in the infectious cycle. Similar results were obtained after superinfection with Sindbis virus. The formation of a new polypeptide with a molecular weight of about 80 X 10(3) was detected. After superinfection with vesicular stomatis virus or Newcastle disease virus the formation of new proteins, characteristic for the early stage of infeciton, was not observed.", "contents": "Inhibition of cellular protein synthesis by simultaneous pretreatment of host cells with fowl plague virus and actinomycin D: a method for studying early protein synthesis of several RNA viruses. A method is described for analysis of viral protein synthesis early after infection when minute amounts of viral proteins are effectively concealed by large amounts of produced host-specific proteins. The method is superior to a radioimmune assay, since all virus-induced proteins can be measured independent of their immunological reactivity. Host-specific protein synthesis can be suppressed by infection with fowl plague virus. Addition of actinomycin C 1.25 h postinfection does not prevent this suppression, but it does block effectively the formation of fowl plague virus-specific proteins. Such cells synthesize only small amounts of cellular proteins, as revealed by polyacrylamide electrophoresis. They can be superinfected with several different enveloped viruses, however, without significant diminution of virus yeilds. In pretreated cells the eclipse is shortened for Semliki Forest virus, Sindbis virus, and vesicular stomatitis virus, but prolonged for Newcastle disease virus. The onset of protein synthesis, specific for the superinfecting virus, could be clearly demonstrated within 1 h after superinfection. At this time, in cells superinfected with Semliki Forest virus, great amounts of NSP 75 (nonstructural protein; molecular weight, 75 X 10(3)) and reduced amounts of the core protein C could be deomonstrated. The precursor glycoprotein NSP 68 is followed by a new polypeptide, NSP 65: three proteins with molecular weights exceeding 100 X 10(3) were observed which are missing later in the infectious cycle. Similar results were obtained after superinfection with Sindbis virus. The formation of a new polypeptide with a molecular weight of about 80 X 10(3) was detected. After superinfection with vesicular stomatis virus or Newcastle disease virus the formation of new proteins, characteristic for the early stage of infeciton, was not observed."} {"id": "PMID:173876", "title": "Ribonucleotide sequence homology among avian oncornaviruses.", "content": "RNA sequence relatedness among avian RNA tumor virus genomes was analyzed by inhibition of DNA-RNA hybrid formation between 3H-labeled 35S viral RNA and an excess of leukemic or normal chicken cell DNA with increasing concentrations of unlabeled 35S viral RNA. The avian viruses tested were Rous associated virus (RAV)-3, avian myeloblastosis virus (AMV), RAV-60, RAV-61, and B-77 sarcoma virus. Hybridization of 3H-labeled 35S AMV RNA with DNA from normal chicken cells was inhibited by unlabeled 35S RAV-0 RNA as effeciently (100%) as by unlabeled AMV RNA. Hybridization between 3H-labeled 35S AMV RNA and DNA from leukemic chicken myeloblasts induced by AMV was suppressed 100 and 68% by unlabeled 35S RNA from AMV and RAV-0, respectively. Hybridization between 3H-labeled RAV-0 and leukemic chicken myeloblast DNA was inhibited 100 and 67% by unlabeled 35S RNA from RAV-0 and AMV, respectively. It appears therefore that the AMV and RAV-0 genomes are 67 to 70% homologous and that AMV hybridizes to RAV-0 like sequences in normal chicken DNA. Hybridization between AMV RNA and leukemic chicken DNA was inhibited 40% by RNA from RAV-60 or RAV-61 and 50% by B-77 RNA. Hybridization between RAV-0 RNA and leukemic chicken DNA was inhibited 80% by RAV-60 or RAV-61 and 70% by B-77 RNA. Hybridization between 3H-labeled 35S RNA from RAV-60 or RAV-61 and leukemic chicken myeloblast DNA was reduced equally by RNA from RAV-60, RAV-61, AMV or RAV-0; this suggests that RNA from RAV-60 and RAV-61 hybridizes with virus-specific sequences in leukemic DNA which are shared by AMV, RAV-0, RAV-60, and RAV-61 RNA'S. Hybridization between 3H-labeled 35S RNA from RAV-61 and normal pheasant DNA was inhibited 100% by homologous viral RNA, 22 TO 26% BY RNA from AMV or RAV-0, and 30 to 33% by RNA from RAV-60 or B-77. Nearly complete inhibition of hybricization between RAV-0 RNA and leukemic chicken DNA by a mixture of AMV and B-77 35S RNAs indicates that the RNA sequences shared by B-77 virus and RAV-0. It appears that different avian RNA tumor virus genomes have from 50 to 80% homology in nucleotide sequences and that the degree of hybridization between normal chicken cell DNA and a given viral RNA can be predicted from the homology that exists between the viral RNA tested and RAV-0 RNA.", "contents": "Ribonucleotide sequence homology among avian oncornaviruses. RNA sequence relatedness among avian RNA tumor virus genomes was analyzed by inhibition of DNA-RNA hybrid formation between 3H-labeled 35S viral RNA and an excess of leukemic or normal chicken cell DNA with increasing concentrations of unlabeled 35S viral RNA. The avian viruses tested were Rous associated virus (RAV)-3, avian myeloblastosis virus (AMV), RAV-60, RAV-61, and B-77 sarcoma virus. Hybridization of 3H-labeled 35S AMV RNA with DNA from normal chicken cells was inhibited by unlabeled 35S RAV-0 RNA as effeciently (100%) as by unlabeled AMV RNA. Hybridization between 3H-labeled 35S AMV RNA and DNA from leukemic chicken myeloblasts induced by AMV was suppressed 100 and 68% by unlabeled 35S RNA from AMV and RAV-0, respectively. Hybridization between 3H-labeled RAV-0 and leukemic chicken myeloblast DNA was inhibited 100 and 67% by unlabeled 35S RNA from RAV-0 and AMV, respectively. It appears therefore that the AMV and RAV-0 genomes are 67 to 70% homologous and that AMV hybridizes to RAV-0 like sequences in normal chicken DNA. Hybridization between AMV RNA and leukemic chicken DNA was inhibited 40% by RNA from RAV-60 or RAV-61 and 50% by B-77 RNA. Hybridization between RAV-0 RNA and leukemic chicken DNA was inhibited 80% by RAV-60 or RAV-61 and 70% by B-77 RNA. Hybridization between 3H-labeled 35S RNA from RAV-60 or RAV-61 and leukemic chicken myeloblast DNA was reduced equally by RNA from RAV-60, RAV-61, AMV or RAV-0; this suggests that RNA from RAV-60 and RAV-61 hybridizes with virus-specific sequences in leukemic DNA which are shared by AMV, RAV-0, RAV-60, and RAV-61 RNA'S. Hybridization between 3H-labeled 35S RNA from RAV-61 and normal pheasant DNA was inhibited 100% by homologous viral RNA, 22 TO 26% BY RNA from AMV or RAV-0, and 30 to 33% by RNA from RAV-60 or B-77. Nearly complete inhibition of hybricization between RAV-0 RNA and leukemic chicken DNA by a mixture of AMV and B-77 35S RNAs indicates that the RNA sequences shared by B-77 virus and RAV-0. It appears that different avian RNA tumor virus genomes have from 50 to 80% homology in nucleotide sequences and that the degree of hybridization between normal chicken cell DNA and a given viral RNA can be predicted from the homology that exists between the viral RNA tested and RAV-0 RNA."} {"id": "PMID:173877", "title": "Origin of the polyoma virus-associated endonuclease.", "content": "Endonuclease activity can be found associated with highly purified preparations of polyoma virus. Evidence has been obtained that this enzyme is not an integral part of the virus but is contributed by the fetal calf serum used in maintenance of polyoma-infected cells. This finding is based on: (i) the lack of virion-associated endonuclease activity when virus is produced using serum-free media and (ii) the production of polyoma antibody which neutralizes fetal calf serum endonuclease activity.", "contents": "Origin of the polyoma virus-associated endonuclease. Endonuclease activity can be found associated with highly purified preparations of polyoma virus. Evidence has been obtained that this enzyme is not an integral part of the virus but is contributed by the fetal calf serum used in maintenance of polyoma-infected cells. This finding is based on: (i) the lack of virion-associated endonuclease activity when virus is produced using serum-free media and (ii) the production of polyoma antibody which neutralizes fetal calf serum endonuclease activity."} {"id": "PMID:173878", "title": "Reactivity of avian RNA tumor viruses with lectins.", "content": "The infectivity of avian RNA tumor viruses was inactivated to varying degrees by treatment with either concanavalin A (Con A) or phytohemagglutinin but not by treatment with wheat germ agglutinin. In general, leukosis viruses reacted preferentially with Con A, whereas sarcoma viruses showed more affinity for phytohemagglutinin. In a more extensive study with subgroup A of Prague Rous sarcoma virus (PR-A), the effect of inactivation by Con A could be specifically prevented by the addition of alpha-methyl-D-mannoside, alpha-methyl-D-glucoside, and N-acetyl-D-glucosamine. These sugars were also capable of eluting [3H]glucosamine-labeled material from disrupted PR-A virus, which was bound to a Con A-sepharose affinity column. A major viral glycoprotein recovered from the column had the same mobility as gp85 in polyacrylamide gel electrophoresis and could be immunoprecipitated with anti-gp85 antiserum. These results suggest that the material reacting with Con A is present on the gp85 component of the viral glycoprotein. The diversity in the reactivity of the glycoproteins of transforming and nontransforming viruses with plant lectins is discussed.", "contents": "Reactivity of avian RNA tumor viruses with lectins. The infectivity of avian RNA tumor viruses was inactivated to varying degrees by treatment with either concanavalin A (Con A) or phytohemagglutinin but not by treatment with wheat germ agglutinin. In general, leukosis viruses reacted preferentially with Con A, whereas sarcoma viruses showed more affinity for phytohemagglutinin. In a more extensive study with subgroup A of Prague Rous sarcoma virus (PR-A), the effect of inactivation by Con A could be specifically prevented by the addition of alpha-methyl-D-mannoside, alpha-methyl-D-glucoside, and N-acetyl-D-glucosamine. These sugars were also capable of eluting [3H]glucosamine-labeled material from disrupted PR-A virus, which was bound to a Con A-sepharose affinity column. A major viral glycoprotein recovered from the column had the same mobility as gp85 in polyacrylamide gel electrophoresis and could be immunoprecipitated with anti-gp85 antiserum. These results suggest that the material reacting with Con A is present on the gp85 component of the viral glycoprotein. The diversity in the reactivity of the glycoproteins of transforming and nontransforming viruses with plant lectins is discussed."} {"id": "PMID:173879", "title": "5' nucleotide sequence of sindbis viral RNA.", "content": "The 5' sequence of Sindbis viral RNA is m (7)G(5') pppApUpGp...", "contents": "5' nucleotide sequence of sindbis viral RNA. The 5' sequence of Sindbis viral RNA is m (7)G(5') pppApUpGp..."} {"id": "PMID:173880", "title": "Comparison of an avian osteopetrosis virus with an avian lymphomatosis virus by RNA-DNA hybridization.", "content": "Myeloblastosis-associated virus (MAV)-2(0), a virus which was derived from avian myeloblastosis virus and induced a high incidence of osteopetrosis, was compared with avian lymphomatosis virus 5938, a recent field isolate which induced a high incidence of lymphomatosis. The following information was obtained. (i) MAV-2(0) induced osteopetrosis, nephroblastoma, and a very low incidence of hepatocellular carcinoma. No difference was seen in the oncogenic spectrum of end point and plaque-purified MAV-2(0). (ii) 125I-labeled RNA sequences from MAV-2(0) formed hybrids with DNA extracted from osteopetrotic bone at a rate suggesting five proviral copies per haploid cell genome. The extent of hybridization of MAV-2(0) RNA with DNA from osteopetrotic tissue was more extensive (87%) than was observed in reactions with DNA from uninfected chicken embryos (52%). (iii) Competition of unlabeled viral RNA in hybridization reactions between the radioactive RNA from the two viruses and their respective proviral sequences present in tumor tissues showed that 15 to 20% of the viral sequences detected in these reactions were unshared. In contrast, no differences were detected in competition analyses of RNA sequences from the two viruses detected in DNA of normal chicken cells. (iv) MAV-2(0) 35S RNA was indistinguishable in size from avian lymphomatosis virus 5938 35S RNA by polyacrylamide gel electrophoresis.", "contents": "Comparison of an avian osteopetrosis virus with an avian lymphomatosis virus by RNA-DNA hybridization. Myeloblastosis-associated virus (MAV)-2(0), a virus which was derived from avian myeloblastosis virus and induced a high incidence of osteopetrosis, was compared with avian lymphomatosis virus 5938, a recent field isolate which induced a high incidence of lymphomatosis. The following information was obtained. (i) MAV-2(0) induced osteopetrosis, nephroblastoma, and a very low incidence of hepatocellular carcinoma. No difference was seen in the oncogenic spectrum of end point and plaque-purified MAV-2(0). (ii) 125I-labeled RNA sequences from MAV-2(0) formed hybrids with DNA extracted from osteopetrotic bone at a rate suggesting five proviral copies per haploid cell genome. The extent of hybridization of MAV-2(0) RNA with DNA from osteopetrotic tissue was more extensive (87%) than was observed in reactions with DNA from uninfected chicken embryos (52%). (iii) Competition of unlabeled viral RNA in hybridization reactions between the radioactive RNA from the two viruses and their respective proviral sequences present in tumor tissues showed that 15 to 20% of the viral sequences detected in these reactions were unshared. In contrast, no differences were detected in competition analyses of RNA sequences from the two viruses detected in DNA of normal chicken cells. (iv) MAV-2(0) 35S RNA was indistinguishable in size from avian lymphomatosis virus 5938 35S RNA by polyacrylamide gel electrophoresis."} {"id": "PMID:173881", "title": "Kinetics of cell fusion induced by a syncytia-producing mutant of herpes simplex virus type I.", "content": "We have isolated a number of plaque-morphology mutants from a strain of herpes simplex virus type I which, unlike the wild type, cause extensive cell fusion during a productive viral infection. After the onset of fusion, there is an exponential decrease in the number of single cells as a function of time after infection. At a multiplicity of infection (MOI) of 3.8 plaque-forming units per cell, fusion begins 5.3 h after infection with the number of single cells decreasing to 10% of the original number 10.2 h after infection. As the MOI is gradually increased from 0.4 to 8, the onset of fusion occurs earlier during infection. However, when the MOI is increased from 8 to 86, the onset of fusion does not occur any earlier. The rate of fusion is independent of the MOI for an MOI greater than 1. The rate of fusion varies linearly with initial cell density up to 3.5 X 10(4) cells/cm2 and is independent of initial cell density at higher cell concentrations. To assay cell fusion we have developed a smiple quantitative assay using a Coulter counter to measure the number of single cells as a function of time after infection. Data obtained using a Coulter counter are similar to those obtained with a microscope assay.", "contents": "Kinetics of cell fusion induced by a syncytia-producing mutant of herpes simplex virus type I. We have isolated a number of plaque-morphology mutants from a strain of herpes simplex virus type I which, unlike the wild type, cause extensive cell fusion during a productive viral infection. After the onset of fusion, there is an exponential decrease in the number of single cells as a function of time after infection. At a multiplicity of infection (MOI) of 3.8 plaque-forming units per cell, fusion begins 5.3 h after infection with the number of single cells decreasing to 10% of the original number 10.2 h after infection. As the MOI is gradually increased from 0.4 to 8, the onset of fusion occurs earlier during infection. However, when the MOI is increased from 8 to 86, the onset of fusion does not occur any earlier. The rate of fusion is independent of the MOI for an MOI greater than 1. The rate of fusion varies linearly with initial cell density up to 3.5 X 10(4) cells/cm2 and is independent of initial cell density at higher cell concentrations. To assay cell fusion we have developed a smiple quantitative assay using a Coulter counter to measure the number of single cells as a function of time after infection. Data obtained using a Coulter counter are similar to those obtained with a microscope assay."} {"id": "PMID:173882", "title": "Interferon treatment of Ehrlich ascites tumor cells: effects on exogenous mRNA translation and tRNA inactivation in the cell extract.", "content": "We reported earlier that in cell extracts that were prepared from interferon-treated Ehrlich ascites tumor cells and preincubated and passed through Sephadex G-25 (S60INT), the translation of exogenous mRNA (viral and host) was impaired and the impairment could be overcome to a large extent by adding a crude tRNA preparation from Ehrlich ascites tumor cells but not from Escherichia coli. We find now that the rate of inactivation of some tRNA's (especially those specific for leucine, lysine, and serine) but not those of many others is faster in S30INT than in corresponding extracts from control cells. This increased rate of tRNA inactivation may perhaps account for the need for added RNA to overcome at least partially the impairment of translation in S30INT. The relationship of the increased rate of tRNA inactivation to the antiviral effect of interferon is unclear. So far no significant difference has been detected in the amount of tRNA needed to overcome the impairment of encephalomyocarditis virus RNA translation in S30INT between tRNA from interferon-treated cells and tRNA from control cells. Futhermore, no difference was found in the rate of inactivation in S30INT between leucine-specific tRNA's from interferon-treated and from control cells. tRNA's specific for leucine and lysine were not inactivated (unless very slowly) during incubation under out conditions in an extract from interferon-treated (or from control) cells unless the extract had been passed through Sephadex G-25 or dialyzed. The translation fo exogenous mRNA was, however, impaired in an extract from interferon-treated cells that had not been passed through Sephadex G-25. This impairment was apparently not overcome by added tRNA.", "contents": "Interferon treatment of Ehrlich ascites tumor cells: effects on exogenous mRNA translation and tRNA inactivation in the cell extract. We reported earlier that in cell extracts that were prepared from interferon-treated Ehrlich ascites tumor cells and preincubated and passed through Sephadex G-25 (S60INT), the translation of exogenous mRNA (viral and host) was impaired and the impairment could be overcome to a large extent by adding a crude tRNA preparation from Ehrlich ascites tumor cells but not from Escherichia coli. We find now that the rate of inactivation of some tRNA's (especially those specific for leucine, lysine, and serine) but not those of many others is faster in S30INT than in corresponding extracts from control cells. This increased rate of tRNA inactivation may perhaps account for the need for added RNA to overcome at least partially the impairment of translation in S30INT. The relationship of the increased rate of tRNA inactivation to the antiviral effect of interferon is unclear. So far no significant difference has been detected in the amount of tRNA needed to overcome the impairment of encephalomyocarditis virus RNA translation in S30INT between tRNA from interferon-treated cells and tRNA from control cells. Futhermore, no difference was found in the rate of inactivation in S30INT between leucine-specific tRNA's from interferon-treated and from control cells. tRNA's specific for leucine and lysine were not inactivated (unless very slowly) during incubation under out conditions in an extract from interferon-treated (or from control) cells unless the extract had been passed through Sephadex G-25 or dialyzed. The translation fo exogenous mRNA was, however, impaired in an extract from interferon-treated cells that had not been passed through Sephadex G-25. This impairment was apparently not overcome by added tRNA."} {"id": "PMID:173883", "title": "Strand-specific transcription of polyoma virus DNA-early in productive infection and in transformed cells.", "content": "The DNA strand origin of nuclear and cytoplasmic polyoma-specific RNA in productively infected mouse cells and in a line of polyoma-transformed hamster cells was determined by hybridization of unlabeled RNA with radioactively labeled separated strands of polyoma DNA. Early in the productive cycle (10 h postinfection) nuclear viral RNA is complementary to only about 40% of the E strand of viral CNA. No RNA complementary to the L strand was detected even when the RNA was first self-annealed to enrich for possible minor species. Early cytoplasmic RNA is complementary to the same 40% of the E strand. Thus, only that part of the poloma genome which codes for early virual messenger RNA appears to be transcribed. Late in infection, nuclear viral RNA is complementary to most or all of the L strand and to at least 60% of the E strand. Late cytoplasmic viral RNA hybridizes to 40 to 45% of the E strand and 50 to 55% of the L strand. The transformed cell nuclear viral RNA is complementary to 60% of the E strand, whereas cytoplasmic RNA is complementary to 40% of the E strand and comprises the same polyoma-specific sequences as are found in RNA early in productive infection. No L strand transcripts could be detected. Thus, in the transformed cells and late in productive infection, viral RNA sequences in the cytoplasm are a specific subset of those in the nucleus.", "contents": "Strand-specific transcription of polyoma virus DNA-early in productive infection and in transformed cells. The DNA strand origin of nuclear and cytoplasmic polyoma-specific RNA in productively infected mouse cells and in a line of polyoma-transformed hamster cells was determined by hybridization of unlabeled RNA with radioactively labeled separated strands of polyoma DNA. Early in the productive cycle (10 h postinfection) nuclear viral RNA is complementary to only about 40% of the E strand of viral CNA. No RNA complementary to the L strand was detected even when the RNA was first self-annealed to enrich for possible minor species. Early cytoplasmic RNA is complementary to the same 40% of the E strand. Thus, only that part of the poloma genome which codes for early virual messenger RNA appears to be transcribed. Late in infection, nuclear viral RNA is complementary to most or all of the L strand and to at least 60% of the E strand. Late cytoplasmic viral RNA hybridizes to 40 to 45% of the E strand and 50 to 55% of the L strand. The transformed cell nuclear viral RNA is complementary to 60% of the E strand, whereas cytoplasmic RNA is complementary to 40% of the E strand and comprises the same polyoma-specific sequences as are found in RNA early in productive infection. No L strand transcripts could be detected. Thus, in the transformed cells and late in productive infection, viral RNA sequences in the cytoplasm are a specific subset of those in the nucleus."} {"id": "PMID:173884", "title": "Chromatin-like structures in polyoma virus and simian virus 10 lytic cycle.", "content": "Nucleoprotein complexes containing viral DNA and cellular histones were extracted from nuclei of permissive cells infected with polyoma virus or simian virus 40 (SV40) and examined by electron microscopy. Polyoma and SV40 nucleoprotein complexes are almost identical. They appear as relaxed circular molecules consisting of 20 to 21 globular particles interconnected by thin filaments. Their contour length in 0.02 M salt is 2.7 times shorter than that of viral DNA form I obtained after dissociation of the proteins in 1 M NaCl. The nucleosomes have an average diameter of 12.5 nm. Each nucleosome contains 175 to 205 DNA base pairs condensed fivefold in length. The nucleosomes are regularly spaced on the circular molecule. The internucleosomal filaments are made of naked DNA, and each filament contains about 55 base pairs. The partial sensitivity of the nucleoprotein complex to cleavage by EcoR1 endonuclease suggests that the nucleosomes are not formed at specific sites on the viral genome. Faster sedimenting nucleoprotein complexes containing replicative intermediates were studied. Isopycnic centrifugation in metrizamide gradients in the absence of aldehyde fixation showed that these molecules conserved the same DNA-to-protein ratio as the form I DNA-containing complexes.", "contents": "Chromatin-like structures in polyoma virus and simian virus 10 lytic cycle. Nucleoprotein complexes containing viral DNA and cellular histones were extracted from nuclei of permissive cells infected with polyoma virus or simian virus 40 (SV40) and examined by electron microscopy. Polyoma and SV40 nucleoprotein complexes are almost identical. They appear as relaxed circular molecules consisting of 20 to 21 globular particles interconnected by thin filaments. Their contour length in 0.02 M salt is 2.7 times shorter than that of viral DNA form I obtained after dissociation of the proteins in 1 M NaCl. The nucleosomes have an average diameter of 12.5 nm. Each nucleosome contains 175 to 205 DNA base pairs condensed fivefold in length. The nucleosomes are regularly spaced on the circular molecule. The internucleosomal filaments are made of naked DNA, and each filament contains about 55 base pairs. The partial sensitivity of the nucleoprotein complex to cleavage by EcoR1 endonuclease suggests that the nucleosomes are not formed at specific sites on the viral genome. Faster sedimenting nucleoprotein complexes containing replicative intermediates were studied. Isopycnic centrifugation in metrizamide gradients in the absence of aldehyde fixation showed that these molecules conserved the same DNA-to-protein ratio as the form I DNA-containing complexes."} {"id": "PMID:173885", "title": "Orientation of the complementary strands of polyoma virus DNA with respect to the DNA physical map.", "content": "The chemical polarities of the two strands of polyoma virus DNA with respect to the DNA physical map have been determined by hybridization of restriction endonuclease fragments specifically labeled with [125I]dCMP at their 3' termini to asymmetric polyoma complementary RNA (the product of in vitro transcription of viral DNA by Escherichia coli RNA polymerase). The orientations of the polyoma-specific stable RNA transcripts present in the cytoplasm of productively linfected mouse cells have been deduced from this result: the 5' ends of the early and late viral transcripts map very near the origin of viral DNA replication.", "contents": "Orientation of the complementary strands of polyoma virus DNA with respect to the DNA physical map. The chemical polarities of the two strands of polyoma virus DNA with respect to the DNA physical map have been determined by hybridization of restriction endonuclease fragments specifically labeled with [125I]dCMP at their 3' termini to asymmetric polyoma complementary RNA (the product of in vitro transcription of viral DNA by Escherichia coli RNA polymerase). The orientations of the polyoma-specific stable RNA transcripts present in the cytoplasm of productively linfected mouse cells have been deduced from this result: the 5' ends of the early and late viral transcripts map very near the origin of viral DNA replication."} {"id": "PMID:173886", "title": "Growth of enveloped RNA viruses in a line of chinese hamster ovary cells with deficient N-acetylglucosaminyltransferase activity.", "content": "Sindbis and vesicular stomatitis viruses were grown in a line (termed 15B) of Chinese hamster ovary (CHO) cells that is deficient in a specific UDP-N-acetyl-glucosamine:glycoprotein N-acetylglucosaminyltransferase. Both viruses replicated normally in the cell line, but the glycoproteins of the released virus migrated faster on sodium didecyl sulfate-polyacrylamide gels than did glycoproteins of virus grown in parent CHO cells. Digestion of the viral glycoproteins with Pronase followed by gel filtration demonstrated that the glycoproteins with Pronase followed by gel filtration demonstrated that the glycopeptides of Sinbis-15B virus were much smaller than the glycopeptides of Sindbis-CHO virus. In addition, Sindbis-15B viral glycopeptides but not Sindbis-CHO viral glycopeptides contained terminal alpha-mannose residues as shown by their susceptibility to alpha-mannosidase digestion. These findings demonstrate that the oligosaccharide units of the glycoproteins of vesicular stomatitis and Sinbis viruses are altered when the viruses are grown in 15B cells. We conclude that the N-acetylglucosaminyltransferase that is missing in 15B cells normally participates in the biosynthesis of the oligosaccharide units of the viral glycoproteins, and in the absence of this enzyme incomplete oligosaccharide chanis are produced. Viruses released from 15B cells appear to retain full infectivity; Sindbis-15B virus, however, showed a significant decrease in hemagglutination titer compared with that of Sindbis-CHO virus.", "contents": "Growth of enveloped RNA viruses in a line of chinese hamster ovary cells with deficient N-acetylglucosaminyltransferase activity. Sindbis and vesicular stomatitis viruses were grown in a line (termed 15B) of Chinese hamster ovary (CHO) cells that is deficient in a specific UDP-N-acetyl-glucosamine:glycoprotein N-acetylglucosaminyltransferase. Both viruses replicated normally in the cell line, but the glycoproteins of the released virus migrated faster on sodium didecyl sulfate-polyacrylamide gels than did glycoproteins of virus grown in parent CHO cells. Digestion of the viral glycoproteins with Pronase followed by gel filtration demonstrated that the glycoproteins with Pronase followed by gel filtration demonstrated that the glycopeptides of Sinbis-15B virus were much smaller than the glycopeptides of Sindbis-CHO virus. In addition, Sindbis-15B viral glycopeptides but not Sindbis-CHO viral glycopeptides contained terminal alpha-mannose residues as shown by their susceptibility to alpha-mannosidase digestion. These findings demonstrate that the oligosaccharide units of the glycoproteins of vesicular stomatitis and Sinbis viruses are altered when the viruses are grown in 15B cells. We conclude that the N-acetylglucosaminyltransferase that is missing in 15B cells normally participates in the biosynthesis of the oligosaccharide units of the viral glycoproteins, and in the absence of this enzyme incomplete oligosaccharide chanis are produced. Viruses released from 15B cells appear to retain full infectivity; Sindbis-15B virus, however, showed a significant decrease in hemagglutination titer compared with that of Sindbis-CHO virus."} {"id": "PMID:173887", "title": "Transformation of hamster kidney cells by BK papovavirus DNA.", "content": "Supercoiled BK papovavirus DNA was shown to transform hamster kidney cells using the calcium phosphate co-precipitation technique. The transformed cells contained intranuclear T-antigen(s) and rescuable virus and produced progressively growing tumors when inoculated into hamsters. A novel finding was the production in tumor-bearing animals of antinuclear antibody, which reacted against normal, untransformed cells; in addition, tumor serum contained antibody against virus-specific T-antigen(s).", "contents": "Transformation of hamster kidney cells by BK papovavirus DNA. Supercoiled BK papovavirus DNA was shown to transform hamster kidney cells using the calcium phosphate co-precipitation technique. The transformed cells contained intranuclear T-antigen(s) and rescuable virus and produced progressively growing tumors when inoculated into hamsters. A novel finding was the production in tumor-bearing animals of antinuclear antibody, which reacted against normal, untransformed cells; in addition, tumor serum contained antibody against virus-specific T-antigen(s)."} {"id": "PMID:173888", "title": "Studies on morphological transformation of BALB/3T3-derived clones by murine leukemia virus.", "content": "We have described a cell line, UC1-B, derived spontaneously from BALB/3T3 mouse embryo cells, which, unlike the standard BALB/3T3, are morphologically transformed and produce bizarre viral forms in response to murine leukemia virus. Although UC1-B and BALB/3T3 are morphologically similar, and both form contact-inhibited monolayers at confluence, the UC1-B cells are partially transformed because: they grow to a slightly higher saturation density than 3T3 cells, they grow in medium lacking serum growth factors, and they produce tumors in mice. Another clone, 12A-3, derived from BALB/3T3, also transforms and produces bizarre viral forms after infection with murine leukemia virus. Unlike UC1-B cells, the 12A3-8 cells are identical in growth properties to BALB/3T3; therefore, a partially altered morphology is not required for the induction of transformation by murine leukemia virus.", "contents": "Studies on morphological transformation of BALB/3T3-derived clones by murine leukemia virus. We have described a cell line, UC1-B, derived spontaneously from BALB/3T3 mouse embryo cells, which, unlike the standard BALB/3T3, are morphologically transformed and produce bizarre viral forms in response to murine leukemia virus. Although UC1-B and BALB/3T3 are morphologically similar, and both form contact-inhibited monolayers at confluence, the UC1-B cells are partially transformed because: they grow to a slightly higher saturation density than 3T3 cells, they grow in medium lacking serum growth factors, and they produce tumors in mice. Another clone, 12A-3, derived from BALB/3T3, also transforms and produces bizarre viral forms after infection with murine leukemia virus. Unlike UC1-B cells, the 12A3-8 cells are identical in growth properties to BALB/3T3; therefore, a partially altered morphology is not required for the induction of transformation by murine leukemia virus."} {"id": "PMID:173889", "title": "Identification of a precursor protein to the major glycoproteins of mouse mammary tumor virus.", "content": "Mouse mammary tumor virus-producing cultures of mouse mammary tumor cells synthesize a viral-related polypeptide of molecular weight of 73,000 (gp 73) which is rapidly labeled during a short pulse but disappears during the chase concomitantly with the appearance of label in the virion glycoproteins gp 49 and gp 37.5/33.5. The addition of the protein synthesis-inhibitor cycloheximide to the chase medium has little effect on this conversion. Treatment of the proposed precursor with alpha-chymotrypsin leads to the formation of a polypeptide of molecular weight 49,000, similar to the major virion glycoprotein. A comparison of tryptic digest maps of the glycoproteins involved supports the hypothesis that both the viral glycoproteins gp 49 and gp 37.5/33.5 are derived from gp 73.", "contents": "Identification of a precursor protein to the major glycoproteins of mouse mammary tumor virus. Mouse mammary tumor virus-producing cultures of mouse mammary tumor cells synthesize a viral-related polypeptide of molecular weight of 73,000 (gp 73) which is rapidly labeled during a short pulse but disappears during the chase concomitantly with the appearance of label in the virion glycoproteins gp 49 and gp 37.5/33.5. The addition of the protein synthesis-inhibitor cycloheximide to the chase medium has little effect on this conversion. Treatment of the proposed precursor with alpha-chymotrypsin leads to the formation of a polypeptide of molecular weight 49,000, similar to the major virion glycoprotein. A comparison of tryptic digest maps of the glycoproteins involved supports the hypothesis that both the viral glycoproteins gp 49 and gp 37.5/33.5 are derived from gp 73."} {"id": "PMID:173890", "title": "Differential inhibition of vesicular stomatitis virus polypeptide synthesis by hypertonic initiation block.", "content": "Synthesis of the vesicular stomatitis virus membrane matrix protein and the glycoprotein is inhibited to a greater extent than the synthesis of the nucleocapsid protein, the nonstructural protein, and the large protein when the rate of peptide chain initiation is reduced by exposure of vesicular stomatitis virus-infected cells to hypertonic medium. It is concluded that the relative sensitivity of individual viral polypeptide synthesis to hypertonic initiation block is independent of the site of synthesis, i.e., whether on membrane-associated or free polyribosomes.", "contents": "Differential inhibition of vesicular stomatitis virus polypeptide synthesis by hypertonic initiation block. Synthesis of the vesicular stomatitis virus membrane matrix protein and the glycoprotein is inhibited to a greater extent than the synthesis of the nucleocapsid protein, the nonstructural protein, and the large protein when the rate of peptide chain initiation is reduced by exposure of vesicular stomatitis virus-infected cells to hypertonic medium. It is concluded that the relative sensitivity of individual viral polypeptide synthesis to hypertonic initiation block is independent of the site of synthesis, i.e., whether on membrane-associated or free polyribosomes."} {"id": "PMID:173891", "title": "5'-terminal sequence of vesicular stomatitis virus mRNA's synthesized in vitro.", "content": "Unmethylated or methylated 12 to 18S mRNA's synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus contain the 5'-terminal hexanucleotide sequence G(5')ppp(5')ApApCpApGp...or m 7G(5')-ppp(5')ApmApCpApGp..., respectively. The implication of these results in relation to the regulation of transcription in vesicular stomatitis virus is discussed.", "contents": "5'-terminal sequence of vesicular stomatitis virus mRNA's synthesized in vitro. Unmethylated or methylated 12 to 18S mRNA's synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus contain the 5'-terminal hexanucleotide sequence G(5')ppp(5')ApApCpApGp...or m 7G(5')-ppp(5')ApmApCpApGp..., respectively. The implication of these results in relation to the regulation of transcription in vesicular stomatitis virus is discussed."} {"id": "PMID:173892", "title": "Quantitative analysis of the rescue of RNA sequences by mammalian type C viruses.", "content": "The specificity and quantitation of the rescue of RNA sequences by mammalian type C viruses has been investigated. Type C virus can package with specificity only type C viral RNA. Type C viruses do not encapsidate with comparable efficiency either type B viral or cellular globin mRNA. Conversely, a non-type C mammalian retravirus, MP-MV, cannot encapsidate type C RNA. A revertant of Kirsten sarcoma virus (Ki-SV)-transformed nonproducer cells which fails to rescue biologically active Ki-SV after superinfection with helper virus had no detectable intracellular Ki-SV-specific RNA. The results suggest specific mechanisms by which type C viral proteins can package type C viral RNA and provide an approach to classifying RNA of potentially defective endogenous retraviruses as type C in origin.", "contents": "Quantitative analysis of the rescue of RNA sequences by mammalian type C viruses. The specificity and quantitation of the rescue of RNA sequences by mammalian type C viruses has been investigated. Type C virus can package with specificity only type C viral RNA. Type C viruses do not encapsidate with comparable efficiency either type B viral or cellular globin mRNA. Conversely, a non-type C mammalian retravirus, MP-MV, cannot encapsidate type C RNA. A revertant of Kirsten sarcoma virus (Ki-SV)-transformed nonproducer cells which fails to rescue biologically active Ki-SV after superinfection with helper virus had no detectable intracellular Ki-SV-specific RNA. The results suggest specific mechanisms by which type C viral proteins can package type C viral RNA and provide an approach to classifying RNA of potentially defective endogenous retraviruses as type C in origin."} {"id": "PMID:173893", "title": "High spontaneous mutation rate of an avian sarcoma virus.", "content": "Three genetically distinct types of chicken sarcoma virus Bratislava 77 (B77 virus) differing in their ability to infect duck cells were identified. B77 virus type I does not infect duck cells; B77 virus type II has a low efficiency of infection of duck cells; and B77 virus type III has a high efficiency of infection of duck cells. B77 viruses type I and III are produced by spontaneous mutation during the growth of B77 virus type II in chicken cells. The spontaneous mutation of B77 virus type II TO B77 virus type III occurs with a high rate (approximately 1 mutation per 50 infected cell generations), requires cell replication, and neither occurs during the synthesis of viral DNA on an RNA template nor during the transcription of progeny viral RNA from the provirus. The rate of spontaneous mutation of B77 virus type II to B77 virus type I is greater than the rate of spontaneous mutation of B77 virus type II to B77 virus type III.", "contents": "High spontaneous mutation rate of an avian sarcoma virus. Three genetically distinct types of chicken sarcoma virus Bratislava 77 (B77 virus) differing in their ability to infect duck cells were identified. B77 virus type I does not infect duck cells; B77 virus type II has a low efficiency of infection of duck cells; and B77 virus type III has a high efficiency of infection of duck cells. B77 viruses type I and III are produced by spontaneous mutation during the growth of B77 virus type II in chicken cells. The spontaneous mutation of B77 virus type II TO B77 virus type III occurs with a high rate (approximately 1 mutation per 50 infected cell generations), requires cell replication, and neither occurs during the synthesis of viral DNA on an RNA template nor during the transcription of progeny viral RNA from the provirus. The rate of spontaneous mutation of B77 virus type II to B77 virus type I is greater than the rate of spontaneous mutation of B77 virus type II to B77 virus type III."} {"id": "PMID:173894", "title": "Virus-dependent glycosylation.", "content": "The oligosaccharides of the membrane glycoproteins of Sindbis virus, vesicular stomatitis virus, and Rous sarcoma virus were compared on the basis of apparent size and sugar composition. It appears that each virus acquires a different set of oligosaccharides during growth in a single type of cell.", "contents": "Virus-dependent glycosylation. The oligosaccharides of the membrane glycoproteins of Sindbis virus, vesicular stomatitis virus, and Rous sarcoma virus were compared on the basis of apparent size and sugar composition. It appears that each virus acquires a different set of oligosaccharides during growth in a single type of cell."} {"id": "PMID:173895", "title": "Fibrous histiocytoma of the bladder.", "content": "A case report of a fibrous histiocytoma of the bladder that presented as total, gross, painless hematuria with compression of the intramural ureter is described. Important pathologic aspects are presented and histiocytic tumors are discussed briefly. Any histiocytic tumor not related to a disease of lipid metabolism is rare and we have found no previous report of a fibrous histiocytoma of the bladder.", "contents": "Fibrous histiocytoma of the bladder. A case report of a fibrous histiocytoma of the bladder that presented as total, gross, painless hematuria with compression of the intramural ureter is described. Important pathologic aspects are presented and histiocytic tumors are discussed briefly. Any histiocytic tumor not related to a disease of lipid metabolism is rare and we have found no previous report of a fibrous histiocytoma of the bladder."} {"id": "PMID:173909", "title": "The stimulatory effect of the boiled supernatant on cyclic AMP formation in synaptosomes from rat cerebral cortex.", "content": "The effect of the boiled supernatant on synaptosomal adenyl cyclase activity of rat cerebral cortex was investigated. The boiled supernatant markedly increased the accumulation of cyclic AMP in synaptosomes when added to adenyl cyclase system by a mechanism presumably unrelated to inhibition of cyclic AMP phosphod iesterase or adenosine triphosphatase. Magnesium ion was required for synaptosomal adenyl cyclase activity and its stimulation by the boiled supernatant. The result discerned by doubl reciprocal plots showed an increase in Vmax value of adenyl cyclase by addition of the boiled supernatant without significantly altering the affinity for substrate. The enzyme activity was not stimulated by dopamine, histamine and serotonin in either the absence and presence of the boiled supernatant.", "contents": "The stimulatory effect of the boiled supernatant on cyclic AMP formation in synaptosomes from rat cerebral cortex. The effect of the boiled supernatant on synaptosomal adenyl cyclase activity of rat cerebral cortex was investigated. The boiled supernatant markedly increased the accumulation of cyclic AMP in synaptosomes when added to adenyl cyclase system by a mechanism presumably unrelated to inhibition of cyclic AMP phosphod iesterase or adenosine triphosphatase. Magnesium ion was required for synaptosomal adenyl cyclase activity and its stimulation by the boiled supernatant. The result discerned by doubl reciprocal plots showed an increase in Vmax value of adenyl cyclase by addition of the boiled supernatant without significantly altering the affinity for substrate. The enzyme activity was not stimulated by dopamine, histamine and serotonin in either the absence and presence of the boiled supernatant."} {"id": "PMID:173910", "title": "Effect of \"drugs for liver disease\" on hepatotoxic action of carbon tetrachloride. I. Changes of lysosomal enzyme levels and effect of protoporphyrin on the levels.", "content": "In order to clarify the action of drugs for liver disease, the effect of protoporphyrin (PP) on CCl4-induced liver injury was studied. Attention was given to the levels of lysosomal enzymes, some components of the liver, and inhibition of enzymes and lysis of lysosomal membranes by lipid peroxides. Administration of PP to CCl4-poisoned rats was found to prevent the decrease in lysosomal lipolytic enzyme level in the liver, but not in other enzyme levels tested. The inhibition of lipolytic enzyme by CCl4 administered may be partially involved in lipid accumulation in the liver. A dose of PP administered to CCl4-poisoned rats for 8 days depressed the neutral lipid content in the liver nearly to the control value. Methyl linoleate hydroperoxide (hydroperoxide) at a lower concentration of 10(-6)% inhibited the lipolytic enzyme acitivity by 30% and in concentrations ranging from 10(-4) to 10(-3)% inhibited beta-glucuronidase activity. Addition of PP to the medium containing 10(-6) to 10(-5)% hydroperoxide and alpha-tocopherol reduced the enzyme inhibition further than in the absence of PP. The hydroperoxide in concentrations varying from 10(-6) to 10(-3)% caused a partial lysis of liver lysosomal membranes, but addition of PP slightly reduced the damage by the hydroperoxide in concentration lower than 10(-5)%.", "contents": "Effect of \"drugs for liver disease\" on hepatotoxic action of carbon tetrachloride. I. Changes of lysosomal enzyme levels and effect of protoporphyrin on the levels. In order to clarify the action of drugs for liver disease, the effect of protoporphyrin (PP) on CCl4-induced liver injury was studied. Attention was given to the levels of lysosomal enzymes, some components of the liver, and inhibition of enzymes and lysis of lysosomal membranes by lipid peroxides. Administration of PP to CCl4-poisoned rats was found to prevent the decrease in lysosomal lipolytic enzyme level in the liver, but not in other enzyme levels tested. The inhibition of lipolytic enzyme by CCl4 administered may be partially involved in lipid accumulation in the liver. A dose of PP administered to CCl4-poisoned rats for 8 days depressed the neutral lipid content in the liver nearly to the control value. Methyl linoleate hydroperoxide (hydroperoxide) at a lower concentration of 10(-6)% inhibited the lipolytic enzyme acitivity by 30% and in concentrations ranging from 10(-4) to 10(-3)% inhibited beta-glucuronidase activity. Addition of PP to the medium containing 10(-6) to 10(-5)% hydroperoxide and alpha-tocopherol reduced the enzyme inhibition further than in the absence of PP. The hydroperoxide in concentrations varying from 10(-6) to 10(-3)% caused a partial lysis of liver lysosomal membranes, but addition of PP slightly reduced the damage by the hydroperoxide in concentration lower than 10(-5)%."} {"id": "PMID:173912", "title": "The effect of danazol in sexual precocity.", "content": "The effect of Danazol, a synthetic 2,3 isoxazol derivative of 17 alpha-ethinyl testosterone, was assessed in three girls and two boys with sexual precocity. Progression of sexual development ceased during administration of Danazol; the effect upon growth rate and skeletal maturation was equivocal. Serum estrogen and progesterone concentrations in the girls were lower during treatment; serum testosterone and dehydroepiandrosterone levels in the boys were also lower. Serum and urinary luteinizing hormone concentrations were inconsistently suppressed. No effect upon follicle-stimulating hormone levels could be demonstrated. Although Danazol appears to inhibit sexual development, this study indicates that the pituitary-gonadal axis is not completely suppressed. Growth rate is not reverted to normal, and virilization may occur among girls. Because undesirable side effects may outweight desirable results, careful consideration is recommended before Danazol is prescribed in the management of sexual precocity.", "contents": "The effect of danazol in sexual precocity. The effect of Danazol, a synthetic 2,3 isoxazol derivative of 17 alpha-ethinyl testosterone, was assessed in three girls and two boys with sexual precocity. Progression of sexual development ceased during administration of Danazol; the effect upon growth rate and skeletal maturation was equivocal. Serum estrogen and progesterone concentrations in the girls were lower during treatment; serum testosterone and dehydroepiandrosterone levels in the boys were also lower. Serum and urinary luteinizing hormone concentrations were inconsistently suppressed. No effect upon follicle-stimulating hormone levels could be demonstrated. Although Danazol appears to inhibit sexual development, this study indicates that the pituitary-gonadal axis is not completely suppressed. Growth rate is not reverted to normal, and virilization may occur among girls. Because undesirable side effects may outweight desirable results, careful consideration is recommended before Danazol is prescribed in the management of sexual precocity."} {"id": "PMID:173913", "title": "Transmission of cytomegalovirus infection with renal allograft.", "content": "Fifty-four patients who received a renal allograft between October 1971 and October 1974 were followed prospectively to correlate pretransplant serum antibody to cytomegalovirus (CMV) with shedding of CMV following transplantation. Twenty-five of 54 patients had antibody demonstrable to CMV using immunofluorescent techniques, but only 20 of 54 using complement-fixing techniques. All 24 who had antibody and survived one month or longer, and seven of nine without antibody but who received a kidney from a seropositive donor shed virus after transplantation, whereas none of 12 individuals without antibody and who received a kidney from a seronegative donor (P less than 0.005) shed virus. Three of eight other seronegative patients for whom donor sera were not available for analysis shed virus. Viremia occurred in eight of ten individuals who developed new antibody after transplantation, versus seven of 24 with antibody prior to transplant (P less than 0.02), and virus shedding in seroconverters from other sites was significantly more persistent than in pretransplant antibody-positive patients. Thus, CMV infection was due either to reactivation of latent infection or was transmitted along with the renal allograft and manifested as a primary infection.", "contents": "Transmission of cytomegalovirus infection with renal allograft. Fifty-four patients who received a renal allograft between October 1971 and October 1974 were followed prospectively to correlate pretransplant serum antibody to cytomegalovirus (CMV) with shedding of CMV following transplantation. Twenty-five of 54 patients had antibody demonstrable to CMV using immunofluorescent techniques, but only 20 of 54 using complement-fixing techniques. All 24 who had antibody and survived one month or longer, and seven of nine without antibody but who received a kidney from a seropositive donor shed virus after transplantation, whereas none of 12 individuals without antibody and who received a kidney from a seronegative donor (P less than 0.005) shed virus. Three of eight other seronegative patients for whom donor sera were not available for analysis shed virus. Viremia occurred in eight of ten individuals who developed new antibody after transplantation, versus seven of 24 with antibody prior to transplant (P less than 0.02), and virus shedding in seroconverters from other sites was significantly more persistent than in pretransplant antibody-positive patients. Thus, CMV infection was due either to reactivation of latent infection or was transmitted along with the renal allograft and manifested as a primary infection."} {"id": "PMID:173915", "title": "[Cataract by galactokinase deficiency (author's transl)].", "content": "In an infant with an inborn defect of the galactokinase, a diffuse turbidity of the lenses was observed before the onset of dietetic therapy at the age of 5 weeks. 2 1/2 years later, the lenses were almost clear, however, typical zonular opacities were revealed at the slit lamp.", "contents": "[Cataract by galactokinase deficiency (author's transl)]. In an infant with an inborn defect of the galactokinase, a diffuse turbidity of the lenses was observed before the onset of dietetic therapy at the age of 5 weeks. 2 1/2 years later, the lenses were almost clear, however, typical zonular opacities were revealed at the slit lamp."} {"id": "PMID:173916", "title": "[Lipid constellation in low density lipoproteins of primary type II hyperlipoproteinemia (author's transl)].", "content": "The lipid composition of purified low density lipoproteins (LDL) was investigated in normal subjects and in type II a and b hyperlipoproteinemia. A significant increase of ester cholesterol in LDL of type II a patients and a decrease of phospholipids in LDL of type II b patients as compared with normal controls, were encountered. The results are compared with other reports from the literature and discussed with regard to the disturbance of LDL metabolism in type II hyperlipoproteinemia.", "contents": "[Lipid constellation in low density lipoproteins of primary type II hyperlipoproteinemia (author's transl)]. The lipid composition of purified low density lipoproteins (LDL) was investigated in normal subjects and in type II a and b hyperlipoproteinemia. A significant increase of ester cholesterol in LDL of type II a patients and a decrease of phospholipids in LDL of type II b patients as compared with normal controls, were encountered. The results are compared with other reports from the literature and discussed with regard to the disturbance of LDL metabolism in type II hyperlipoproteinemia."} {"id": "PMID:173918", "title": "Husbandry and observation methods of a breeding colony of marmosets (Callithrix jacchus) for behavioural research.", "content": "By allowing families to increase in size, co-operation between parents and adolescents in infant care was encouraged. Young adult pairs were subsequently created with these marmosets which had experience of handling infants to provide a stable basis for breeding 2nd and 3rd generation marmosets in captivity.", "contents": "Husbandry and observation methods of a breeding colony of marmosets (Callithrix jacchus) for behavioural research. By allowing families to increase in size, co-operation between parents and adolescents in infant care was encouraged. Young adult pairs were subsequently created with these marmosets which had experience of handling infants to provide a stable basis for breeding 2nd and 3rd generation marmosets in captivity."} {"id": "PMID:173919", "title": "Diaphragmatic herniation of the liver in macaques demonstrated by intravenous hepatography.", "content": "A suspected diagnosis of diaphragmatic herniation of the liver in 2 monkeys (Macaca fascicularis and Macaca mulatta) was confirmed radiographically by using various contrast media. Experimental compound AG 60.99, which is selectively concentrated in the liver and spleen, allowed excellent visualization of these 2 organs and confirmed the presence of a portion of the liver in the right thorax. Cholografin Meglumine was subsequently utilized to determine the location of the gall bladder. Other potential uses for AG 60.99 were discussed.", "contents": "Diaphragmatic herniation of the liver in macaques demonstrated by intravenous hepatography. A suspected diagnosis of diaphragmatic herniation of the liver in 2 monkeys (Macaca fascicularis and Macaca mulatta) was confirmed radiographically by using various contrast media. Experimental compound AG 60.99, which is selectively concentrated in the liver and spleen, allowed excellent visualization of these 2 organs and confirmed the presence of a portion of the liver in the right thorax. Cholografin Meglumine was subsequently utilized to determine the location of the gall bladder. Other potential uses for AG 60.99 were discussed."} {"id": "PMID:173925", "title": "Ultrastructural localization of peroxidatic catalase in human peripheral blood leukocytes.", "content": "Localization of peroxidatic catalase in human peripheral blood leukocytes was accomplished by the assessment of alkaline diaminobenzidine reaction in the cytoplasmic granules of normal and acatalasemic leukocytes. A modified cytochemical procedure of Novikoff and Goldfischer (Novikoff AB, Goldfischer S: J Histochem Cytochem 17:675, 1969) and of Fahimi (Fahimi HD:J Cell Biol 43:275, 1969) was employed to improve the specificity of alkaline diaminobenzidine test for catalase. Diaminobenzidine-positive reaction for peroxidative catalase was observed in large and medium-sized granules in the cytoplasm of normal neutrophils, but a striking and notable absence of this reaction was observed in acatalasemic neutrophils. The test for myeloperoxidase, with the diaminobenzide reaction performed at neutrality, disclosed positively stained granules in both normal and acatalasemic neutrophils. Similarities in size and configuration of the positively stained granules for these enzymes suggest that catalase is sequestered in organelles which may be primary or azurophilic granules. Myeloperoxidase has been shown to be localized in the primary granules by others. It is possible that catalase and myeloperoxidase may be sequestered together or separately in these granules, but the present data do not permit us to draw this distinction. The ultrastructural localization of peroxidatic catalase and myeloperoxidase has been attempted in eosinophils, lymphocytes, and platelets, and the observations are compared with those of neutrophilic granules. The localization of peroxidatic catalase in monocytes could not be assessed satisfactorily because of the difficulties encountered in proper sampling of these cells.", "contents": "Ultrastructural localization of peroxidatic catalase in human peripheral blood leukocytes. Localization of peroxidatic catalase in human peripheral blood leukocytes was accomplished by the assessment of alkaline diaminobenzidine reaction in the cytoplasmic granules of normal and acatalasemic leukocytes. A modified cytochemical procedure of Novikoff and Goldfischer (Novikoff AB, Goldfischer S: J Histochem Cytochem 17:675, 1969) and of Fahimi (Fahimi HD:J Cell Biol 43:275, 1969) was employed to improve the specificity of alkaline diaminobenzidine test for catalase. Diaminobenzidine-positive reaction for peroxidative catalase was observed in large and medium-sized granules in the cytoplasm of normal neutrophils, but a striking and notable absence of this reaction was observed in acatalasemic neutrophils. The test for myeloperoxidase, with the diaminobenzide reaction performed at neutrality, disclosed positively stained granules in both normal and acatalasemic neutrophils. Similarities in size and configuration of the positively stained granules for these enzymes suggest that catalase is sequestered in organelles which may be primary or azurophilic granules. Myeloperoxidase has been shown to be localized in the primary granules by others. It is possible that catalase and myeloperoxidase may be sequestered together or separately in these granules, but the present data do not permit us to draw this distinction. The ultrastructural localization of peroxidatic catalase and myeloperoxidase has been attempted in eosinophils, lymphocytes, and platelets, and the observations are compared with those of neutrophilic granules. The localization of peroxidatic catalase in monocytes could not be assessed satisfactorily because of the difficulties encountered in proper sampling of these cells."} {"id": "PMID:173927", "title": "Does myosin-substrate interaction in vitro result in a delocalized conformation change?", "content": "The effect of substrate on the far UV (185-250 nm) and near UV (250-325 nm) circular dichroism (CD) of myosin and heavy meromyosin (HMM) was studied. The following results were obtained with the addition of ATP (during various conditions of hydrolysis), ADP, and pyrophosphate: (1) no changes were observed in the far UV CD, (2) ATP and ADP perturbed the near UV CD only at spectral regions below 280 nm coinciding with the regions of their optical activity, (3) the optically inactive pyrophosphate caused no change in the near UV CD, and (4) myosin and HMM gave exactly the same results. These results suggest that myosin-substrate interaction in vitro does not result in a delocalized conformational change.", "contents": "Does myosin-substrate interaction in vitro result in a delocalized conformation change? The effect of substrate on the far UV (185-250 nm) and near UV (250-325 nm) circular dichroism (CD) of myosin and heavy meromyosin (HMM) was studied. The following results were obtained with the addition of ATP (during various conditions of hydrolysis), ADP, and pyrophosphate: (1) no changes were observed in the far UV CD, (2) ATP and ADP perturbed the near UV CD only at spectral regions below 280 nm coinciding with the regions of their optical activity, (3) the optically inactive pyrophosphate caused no change in the near UV CD, and (4) myosin and HMM gave exactly the same results. These results suggest that myosin-substrate interaction in vitro does not result in a delocalized conformational change."} {"id": "PMID:173933", "title": "Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes.", "content": "A series of cases of lung cancer were analyzed, with particular attention to the relationship between the presence of lymph node metastases and the prognosis for surgical intervention. The cases are classified into four clinical stages and a detailed classification of histologically proved lymph node metastasis and pleural involvement is presented. Results indicate that the presence of mediastinal lymph node metastasis, especially in cases with squamous-cell carcinoma and negative subcarinal lymph node, does not contraindicate surgical treatment.", "contents": "Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes. A series of cases of lung cancer were analyzed, with particular attention to the relationship between the presence of lymph node metastases and the prognosis for surgical intervention. The cases are classified into four clinical stages and a detailed classification of histologically proved lymph node metastasis and pleural involvement is presented. Results indicate that the presence of mediastinal lymph node metastasis, especially in cases with squamous-cell carcinoma and negative subcarinal lymph node, does not contraindicate surgical treatment."} {"id": "PMID:173934", "title": "The use of bronchoscopic sponge biopsy in the diagnosis of pulmonary neoplasms.", "content": "A modified method of transbronchoscopic sponge biopsy is presented a series of 212 patients is discussed. A diagnostic accuracy rate of 89 per cent was obtained in the 159 cases of proved carcinoma. False-positive and false-negative results are discussed. This technique was found to be an easy, rapid, accurate, and inexpensive method of obtaining samples for cytologic evaluation in the preoperative work-up of patients with suspected pulmonary malignancies.", "contents": "The use of bronchoscopic sponge biopsy in the diagnosis of pulmonary neoplasms. A modified method of transbronchoscopic sponge biopsy is presented a series of 212 patients is discussed. A diagnostic accuracy rate of 89 per cent was obtained in the 159 cases of proved carcinoma. False-positive and false-negative results are discussed. This technique was found to be an easy, rapid, accurate, and inexpensive method of obtaining samples for cytologic evaluation in the preoperative work-up of patients with suspected pulmonary malignancies."} {"id": "PMID:173935", "title": "Carinal resection. A report of two cases and a description of the anesthetic technique.", "content": "Two cases of carinal tumor managed by resection and primary anastomosis are presented. Their course is discussed and a description of an anesthetic technique which obviates the need for cardiopulmonary bypass is presented. The principles of carinal surgery are discussed, emphasizing expert anesthesia and resection line control by frozen-tissue examination.", "contents": "Carinal resection. A report of two cases and a description of the anesthetic technique. Two cases of carinal tumor managed by resection and primary anastomosis are presented. Their course is discussed and a description of an anesthetic technique which obviates the need for cardiopulmonary bypass is presented. The principles of carinal surgery are discussed, emphasizing expert anesthesia and resection line control by frozen-tissue examination."} {"id": "PMID:173936", "title": "International arbovirus research.", "content": "International cooperation in arbovirus research became increasingly prominent shortly after it was found in the early 1940's, that antigenic relationships existed among certain viruses isolated in different areas of thw world. The interest of a number of scientists and of a private organization led to the establishment of an international information exchange and to the preparation of an international catalogue of arboviruses including certain other viruses of vertebrates. International cooperation was fostered by the interest taken in these agents by the World Health Organization and the creation by this agency of an international net of collaborating laboratories with assigned areas of the world. A number of recent problems have been revealed and solved, or partly solved by this international effort, among which are questions relating to: the Marburg agent disease, the existence of an antigenic relationship between rabies virus and some arboviruses, aspects of the ecology or viruses in the California, Uukuniemi and Kemerovo groups, as well as several unanticipated antigenic relationships among viruses. Numerous questions still remain the solution of which might be expedited by continued and increased cooperative international effort such as overwintering or survival of viruses under unfavorable circumstances, pathogenic potential for man and domestic animals of certain viruses, role on chronic illnesses, establishment of the etiology of certain diseases and investigations of the basic properties of viruses, particularly of the Bunyaviridae.", "contents": "International arbovirus research. International cooperation in arbovirus research became increasingly prominent shortly after it was found in the early 1940's, that antigenic relationships existed among certain viruses isolated in different areas of thw world. The interest of a number of scientists and of a private organization led to the establishment of an international information exchange and to the preparation of an international catalogue of arboviruses including certain other viruses of vertebrates. International cooperation was fostered by the interest taken in these agents by the World Health Organization and the creation by this agency of an international net of collaborating laboratories with assigned areas of the world. A number of recent problems have been revealed and solved, or partly solved by this international effort, among which are questions relating to: the Marburg agent disease, the existence of an antigenic relationship between rabies virus and some arboviruses, aspects of the ecology or viruses in the California, Uukuniemi and Kemerovo groups, as well as several unanticipated antigenic relationships among viruses. Numerous questions still remain the solution of which might be expedited by continued and increased cooperative international effort such as overwintering or survival of viruses under unfavorable circumstances, pathogenic potential for man and domestic animals of certain viruses, role on chronic illnesses, establishment of the etiology of certain diseases and investigations of the basic properties of viruses, particularly of the Bunyaviridae."} {"id": "PMID:173938", "title": "Tick-borne viruses associated with seabirds in North America and related islands.", "content": "About 18 tickborne viruses associated with seabirds are known from Canada, Mexico, the Antilles, and the United States, including its oceanic islands. Antigenic groups to which these viruses belong are Hughes, B, Sakhalin, Uukuniemi, Kemerovo, Nyamani and Quaranfil. Members of the last two groups are known in the Western Hemisphere only from Central Pacific Islands and may reflect intrusion of elements of the Australian Region. In the areas under discussion, antibody surveys have been minimal, but there is some indication of human exposure to agents of the Kemerovo group. Members of the Hughes, Nyamanini, and Quaranfil groups are all argasid tick viruses, largely tropical or subtropical in distribution, and associated particularly with gulls and terns (Laridae). The remainder, with the exception of Mono Lake (Kemerovo group, Chenuda Subgroup), which may be a virus of inland birds, are ixodid tick viruses associated mostly with seabirds of the polar or subpolar regions. All of these viruses are seen as acted upon by a common pattern of geographic and biotic factors that influences antigenic diversity of the virus and favors development of strong insular variants.", "contents": "Tick-borne viruses associated with seabirds in North America and related islands. About 18 tickborne viruses associated with seabirds are known from Canada, Mexico, the Antilles, and the United States, including its oceanic islands. Antigenic groups to which these viruses belong are Hughes, B, Sakhalin, Uukuniemi, Kemerovo, Nyamani and Quaranfil. Members of the last two groups are known in the Western Hemisphere only from Central Pacific Islands and may reflect intrusion of elements of the Australian Region. In the areas under discussion, antibody surveys have been minimal, but there is some indication of human exposure to agents of the Kemerovo group. Members of the Hughes, Nyamanini, and Quaranfil groups are all argasid tick viruses, largely tropical or subtropical in distribution, and associated particularly with gulls and terns (Laridae). The remainder, with the exception of Mono Lake (Kemerovo group, Chenuda Subgroup), which may be a virus of inland birds, are ixodid tick viruses associated mostly with seabirds of the polar or subpolar regions. All of these viruses are seen as acted upon by a common pattern of geographic and biotic factors that influences antigenic diversity of the virus and favors development of strong insular variants."} {"id": "PMID:173939", "title": "Tick-borne viruses in Finland.", "content": "Ixodes ricinus is the only one of six tick species reported from Finland found to carry viruses. It transmits tick-borne encephalitis and Uukuniemi viruses, and transmission of a Kemerovo group virus is suggested by antibody findings. Tick-borne encephalitis is common only in the SW-archipelago; it is also found near the SE-boarder but is very rare elsewhere. In contrast, Uukuniemi virus is common throughout the distribution area of I. ricinus, being commoner on the mainland than in the archipelago. Medium, large and small mammals participate in the cycle of tick-borne encephalitis virus, though birds are not excluded and apparently they act as host to the Uukuniemi virus. The encephalitis virus causes clinical illness in man, with cases limited mostly to the SW-archipelago; the disease is a relatively mild form of tick-borne encephalitis, with biphasic and meningeal symptoms dominating.", "contents": "Tick-borne viruses in Finland. Ixodes ricinus is the only one of six tick species reported from Finland found to carry viruses. It transmits tick-borne encephalitis and Uukuniemi viruses, and transmission of a Kemerovo group virus is suggested by antibody findings. Tick-borne encephalitis is common only in the SW-archipelago; it is also found near the SE-boarder but is very rare elsewhere. In contrast, Uukuniemi virus is common throughout the distribution area of I. ricinus, being commoner on the mainland than in the archipelago. Medium, large and small mammals participate in the cycle of tick-borne encephalitis virus, though birds are not excluded and apparently they act as host to the Uukuniemi virus. The encephalitis virus causes clinical illness in man, with cases limited mostly to the SW-archipelago; the disease is a relatively mild form of tick-borne encephalitis, with biphasic and meningeal symptoms dominating."} {"id": "PMID:173940", "title": "Comparative aspects of the replication of alphaviruses and poliovirus.", "content": "The replication of both alpha- and picornaviruses results in the production of plus-stranded viral progeny. Each of these two classes of virus devotes about the same amount of viral genetic information to structural proteins but the alphaviruses use more genetic information for non-virion proteins. This additional information may be required because the alphaviruses have a much broader host range. Alternatively, the additional information may be required for interrupted transcription that yields a subgenomic mRNA that encodes all of the alphaviral structural proteins. This subgenomic mRNA allows preferential synthesis of a precursor af all virion proteins. Cleavage of this precursor has been observed during in vitro protein synthesis and can be prevented by an appropriate temperature-sensitive mutation.", "contents": "Comparative aspects of the replication of alphaviruses and poliovirus. The replication of both alpha- and picornaviruses results in the production of plus-stranded viral progeny. Each of these two classes of virus devotes about the same amount of viral genetic information to structural proteins but the alphaviruses use more genetic information for non-virion proteins. This additional information may be required because the alphaviruses have a much broader host range. Alternatively, the additional information may be required for interrupted transcription that yields a subgenomic mRNA that encodes all of the alphaviral structural proteins. This subgenomic mRNA allows preferential synthesis of a precursor af all virion proteins. Cleavage of this precursor has been observed during in vitro protein synthesis and can be prevented by an appropriate temperature-sensitive mutation."} {"id": "PMID:173941", "title": "Translation of the genes for the structural proteins of alphaviruses.", "content": "Synthesis of the structural proteins of Semliki Forest virus by a cell-free system derived from mouse L-cells and programmed by intracellular 26S RNA is described. This polycistronic RNA is translated in vitro into several discrete polypeptides. The identity of these polypeptides as the structural proteins of the virus was established by polyacrylamide gel electrophoresis, immunoprecipitation and tryptic peptide mapping. Studies using formyl--e135S]methionyl-tRNAf as precursor, and using diphtheria toxin and NAD to inhibit elongation, showed that 26S RNA contains only a single initiation site at, or near, the 5' end of the core protein cistron. Experiments in infected cells under conditions of synchronous initiation revealed that the order of the structural protein genes in 26S RNA is core-E3-E2-E1 in the 5' leads to 3' direction.", "contents": "Translation of the genes for the structural proteins of alphaviruses. Synthesis of the structural proteins of Semliki Forest virus by a cell-free system derived from mouse L-cells and programmed by intracellular 26S RNA is described. This polycistronic RNA is translated in vitro into several discrete polypeptides. The identity of these polypeptides as the structural proteins of the virus was established by polyacrylamide gel electrophoresis, immunoprecipitation and tryptic peptide mapping. Studies using formyl--e135S]methionyl-tRNAf as precursor, and using diphtheria toxin and NAD to inhibit elongation, showed that 26S RNA contains only a single initiation site at, or near, the 5' end of the core protein cistron. Experiments in infected cells under conditions of synchronous initiation revealed that the order of the structural protein genes in 26S RNA is core-E3-E2-E1 in the 5' leads to 3' direction."} {"id": "PMID:173944", "title": "[Surgical treatment of malformations of the hand (author's transl)].", "content": "The frequency of malformations of the hand is estimated at 0.5 percent of live births. The course of early developmental processes makes early correction advisable. Knowledge of the special anatomy and mastery of the microsurgical operation techniques makes this possible. The main indications and methods that hve been tested are discussed.", "contents": "[Surgical treatment of malformations of the hand (author's transl)]. The frequency of malformations of the hand is estimated at 0.5 percent of live births. The course of early developmental processes makes early correction advisable. Knowledge of the special anatomy and mastery of the microsurgical operation techniques makes this possible. The main indications and methods that hve been tested are discussed."} {"id": "PMID:173946", "title": "[Carcinochemotherapy in pediatric surgery (author's transl)].", "content": "One hundred sixteen children with malignant tumors were treated by surgery and additional chemotherapy from 1969 to 1974. The chemotherapy was standardized as far as possible for the commonest tumors of childhood (neuroblastoma, Wilm's tumor rhabdomyosarcoma, osteosarcoma). The results are presented in detail.", "contents": "[Carcinochemotherapy in pediatric surgery (author's transl)]. One hundred sixteen children with malignant tumors were treated by surgery and additional chemotherapy from 1969 to 1974. The chemotherapy was standardized as far as possible for the commonest tumors of childhood (neuroblastoma, Wilm's tumor rhabdomyosarcoma, osteosarcoma). The results are presented in detail."} {"id": "PMID:173947", "title": "[Juvenile tonsillectomy and leukemia].", "content": "Among 305 children with leukemia, between one and fourteen years old, authors found 8 and in a comparative group (\"individual matched pairs\") 40 children with removed tonsils. The difference (2.62% tonsillectomized children in the leukemia-group, 13.11% in the comparative group) is highly significant. The frequency of tonsillectomy in childhood in Germany corresponds to the percentage of 13.11%. It has to be discussed, if there exists a causality between the state of the tonsils and the frequency of leukemia in childhood. The authors suggest further investigations of this highly interesting subject.", "contents": "[Juvenile tonsillectomy and leukemia]. Among 305 children with leukemia, between one and fourteen years old, authors found 8 and in a comparative group (\"individual matched pairs\") 40 children with removed tonsils. The difference (2.62% tonsillectomized children in the leukemia-group, 13.11% in the comparative group) is highly significant. The frequency of tonsillectomy in childhood in Germany corresponds to the percentage of 13.11%. It has to be discussed, if there exists a causality between the state of the tonsils and the frequency of leukemia in childhood. The authors suggest further investigations of this highly interesting subject."} {"id": "PMID:173960", "title": "Uptake and metabolism of exogenous eicosa-8,11,14-trienoic acid in minimal deviation hepatoma 7288 C cells.", "content": "Minimal deviation hepatoma 7288 C cells were cultured in Swim's medium containing 10% serum for 48 hr. The growth medium was replaced with serum free media containing different concentrations of [1-14C] eicosa-8,11,14-trienoic acid and the cells were incubated for 24 hr. Incorporation into cell lipids, oxidation to CO2, and desaturation to arachidonic acid were studied. The oxidation of the acid was very low. It was preferentially incorporated into the polar lipids of the cell. The incorporation depended on the number of cells and fatty acid concentration. Saturation of the cells with the acid was reached when 144.7 nmoles per mg of cellular protein were incorporated. The acid was desaturated readily to arachidonic acid. The nmoles of eicosatrienoic acid converted to arachidonic acid per mg of cellular protein were hyperbolic function of the acid incorporated. Maximal desaturation, 23 nmoles per mg of cellular protein, was reached when the cells were saturated with the acid. The calculations of the desaturation capacity and of the endogenous pool of eicosatrienoic acid available for desaturation in the cell are discussed.", "contents": "Uptake and metabolism of exogenous eicosa-8,11,14-trienoic acid in minimal deviation hepatoma 7288 C cells. Minimal deviation hepatoma 7288 C cells were cultured in Swim's medium containing 10% serum for 48 hr. The growth medium was replaced with serum free media containing different concentrations of [1-14C] eicosa-8,11,14-trienoic acid and the cells were incubated for 24 hr. Incorporation into cell lipids, oxidation to CO2, and desaturation to arachidonic acid were studied. The oxidation of the acid was very low. It was preferentially incorporated into the polar lipids of the cell. The incorporation depended on the number of cells and fatty acid concentration. Saturation of the cells with the acid was reached when 144.7 nmoles per mg of cellular protein were incorporated. The acid was desaturated readily to arachidonic acid. The nmoles of eicosatrienoic acid converted to arachidonic acid per mg of cellular protein were hyperbolic function of the acid incorporated. Maximal desaturation, 23 nmoles per mg of cellular protein, was reached when the cells were saturated with the acid. The calculations of the desaturation capacity and of the endogenous pool of eicosatrienoic acid available for desaturation in the cell are discussed."} {"id": "PMID:173961", "title": "Hepatoma, host liver, and normal rat liver phospholipids as affected by diet.", "content": "Individual phospholipid classes derived from hepatoma, host liver, and normal liver of rats maintained on chow and fat free diets were examined in detail and the sphingomyelin and phosphoglyceride structures compared. The concentration of hepatoma spingomyelin was higher while phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and diphosphatidylglycerol were only one-fourth to one-half normal liver concentrations, irrespective of diet. Hepatoma phosphatidylcholine, phosphatidylethanolamine, phosphatidyl-serine, and phosphatidylinositol contained higher percentages of 18:1 and, except phosphatidylinositol, much lower percentages of most polyunsaturated fatty acids than liver. The 1-position of host liver phosphatidylcholine and phosphatidylethanolamine, normal liver phosphatidylcholine and phosphatidylethanolamine, and hepatoma phosphatidylcholine from animals on both diets had the same approximate fatty acid composition, but the percentage of 16:0 in hepatoma phosphatidylethanolamine was reduced dramatically. The low percentage of 16:0 at the 1-position of both phosphatidylethanolamine and triglycerides suggests that the 1-position fatty acids of these two classes may have a similar origin. The fat free diet reduced the percentage of 18:2 in liver diphosphatidylglycerol 3-fold and the decrease was offset by increased percentages of 16:1 and 18:1; whereas the very low percentage of 18:2 in hepatoma diphosphatidylglycerol was offset by increased percentages of 18:0 and 16:0. Liver phosphatidylinositol and phosphatidylcholine from the animals fed the fat free diet contained the highest percentage of 20:3, which replaced 20:4. Hepatoma sphingomyelin contained a much higher concentration of 24:0 and 24:1 than liver. The hepatoma sphingomyelin also contained a C-24 dienoic acid, which was not detected in host and normal liver. Host liver contained a higher percentage of 22:6 than normal liver. The diglycerides derived from host liver PC contained a significantly higher percentage of carbon number 38 than normal liver. Diglycerides derived from hepatoma phosphatidylcholine and phosphatidylethanolamine exhibited a 1-random-2-random distribution of fatty acids, whereas diglycerides from liver phosphatidylcholine and phosphatidylethanolamine showed pairing of specific fatty acids.", "contents": "Hepatoma, host liver, and normal rat liver phospholipids as affected by diet. Individual phospholipid classes derived from hepatoma, host liver, and normal liver of rats maintained on chow and fat free diets were examined in detail and the sphingomyelin and phosphoglyceride structures compared. The concentration of hepatoma spingomyelin was higher while phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and diphosphatidylglycerol were only one-fourth to one-half normal liver concentrations, irrespective of diet. Hepatoma phosphatidylcholine, phosphatidylethanolamine, phosphatidyl-serine, and phosphatidylinositol contained higher percentages of 18:1 and, except phosphatidylinositol, much lower percentages of most polyunsaturated fatty acids than liver. The 1-position of host liver phosphatidylcholine and phosphatidylethanolamine, normal liver phosphatidylcholine and phosphatidylethanolamine, and hepatoma phosphatidylcholine from animals on both diets had the same approximate fatty acid composition, but the percentage of 16:0 in hepatoma phosphatidylethanolamine was reduced dramatically. The low percentage of 16:0 at the 1-position of both phosphatidylethanolamine and triglycerides suggests that the 1-position fatty acids of these two classes may have a similar origin. The fat free diet reduced the percentage of 18:2 in liver diphosphatidylglycerol 3-fold and the decrease was offset by increased percentages of 16:1 and 18:1; whereas the very low percentage of 18:2 in hepatoma diphosphatidylglycerol was offset by increased percentages of 18:0 and 16:0. Liver phosphatidylinositol and phosphatidylcholine from the animals fed the fat free diet contained the highest percentage of 20:3, which replaced 20:4. Hepatoma sphingomyelin contained a much higher concentration of 24:0 and 24:1 than liver. The hepatoma sphingomyelin also contained a C-24 dienoic acid, which was not detected in host and normal liver. Host liver contained a higher percentage of 22:6 than normal liver. The diglycerides derived from host liver PC contained a significantly higher percentage of carbon number 38 than normal liver. Diglycerides derived from hepatoma phosphatidylcholine and phosphatidylethanolamine exhibited a 1-random-2-random distribution of fatty acids, whereas diglycerides from liver phosphatidylcholine and phosphatidylethanolamine showed pairing of specific fatty acids."} {"id": "PMID:173962", "title": "Hepatoma, host liver, and normal rat liver lipids: distribution of isomeric monoene fatty acids in individual lipid classes.", "content": "Monoenoic acid fractions were isolated from phosphatidycholine, phosphatidylethanolamine, triglycerides, and cholesteryl esters of hepatoma 7288CTC, host liver, and normal liver from animals maintained on chow and fat free diets. Hexadecanoate (16:1), octadecenoate (18:1), and eisosenoate (20:1) fractions were analyzed quantitatively for their isomeric composition. The fat free diet had little or no effect relative to the chow diet on the isomeric composition of 16:1, 18:1, and 20:1 from any lipid class in either heptoma, host liver, or normal liver. Host livers were reduced in palmitoleic acid, and oleic and eicos-11-enoic acids were increased relative to normal liver. The 16:1 fraction from triglyceride of normal liver, host liver, and hepatoma contained 90, 80, and 75% palmitoleic acid, respectively. The 20:1 fraction from triglycerides of normal liver, host liver, and hepatoma contained ca. 55, 70, and 60% eicos-11-enoic acid, respectively, with the remainder consisting of eicos-13-enoic acid. The proportion of vaccenic acid in the 18:1 fraction was 60, 50, 20, and 25% for phosphatidylethanolamine, phosphatidylcholine, triglycerides, and cholesteryl esters, respectively, with oleic acid making up the balance. In contrast, all hepatoma lipid classes exhibited the same proportion of oleic (70%) and vaccenic (30%) acids. These data appear to be the first to demonstrate lipid class specificity for isomeric octadecenoic acids in normal liver and the loss of this specificity in a neoplasm.", "contents": "Hepatoma, host liver, and normal rat liver lipids: distribution of isomeric monoene fatty acids in individual lipid classes. Monoenoic acid fractions were isolated from phosphatidycholine, phosphatidylethanolamine, triglycerides, and cholesteryl esters of hepatoma 7288CTC, host liver, and normal liver from animals maintained on chow and fat free diets. Hexadecanoate (16:1), octadecenoate (18:1), and eisosenoate (20:1) fractions were analyzed quantitatively for their isomeric composition. The fat free diet had little or no effect relative to the chow diet on the isomeric composition of 16:1, 18:1, and 20:1 from any lipid class in either heptoma, host liver, or normal liver. Host livers were reduced in palmitoleic acid, and oleic and eicos-11-enoic acids were increased relative to normal liver. The 16:1 fraction from triglyceride of normal liver, host liver, and hepatoma contained 90, 80, and 75% palmitoleic acid, respectively. The 20:1 fraction from triglycerides of normal liver, host liver, and hepatoma contained ca. 55, 70, and 60% eicos-11-enoic acid, respectively, with the remainder consisting of eicos-13-enoic acid. The proportion of vaccenic acid in the 18:1 fraction was 60, 50, 20, and 25% for phosphatidylethanolamine, phosphatidylcholine, triglycerides, and cholesteryl esters, respectively, with oleic acid making up the balance. In contrast, all hepatoma lipid classes exhibited the same proportion of oleic (70%) and vaccenic (30%) acids. These data appear to be the first to demonstrate lipid class specificity for isomeric octadecenoic acids in normal liver and the loss of this specificity in a neoplasm."} {"id": "PMID:173963", "title": "Lipid and lipoprotein measurements in a normal adult American population.", "content": "From a parent population of 774, a subpopulation of 160 normal adults ages 27-66 was randomly selected, 20 from each decade and sex. A detailed comparison was made by analytic ultracentrifugation and complete agarose gel electrophoresis on serum and the 1.006 g/ml top and bottom preparative ultracentrifuge lipoprotein fractions. The latter was internally standardized by total lipid and plasma total cholesterol and triglyceride determinations giving normal reference lipoprotein values. The reading procedure allowed the identification and quantification of floating beta and sinking pre-beta. In the subpopulation, there were two of the former and 13 of the latter. For large scale clinical application of such quantitative lipoprotein electrophoresis full automation of the microdensitometry and calculations will be required.", "contents": "Lipid and lipoprotein measurements in a normal adult American population. From a parent population of 774, a subpopulation of 160 normal adults ages 27-66 was randomly selected, 20 from each decade and sex. A detailed comparison was made by analytic ultracentrifugation and complete agarose gel electrophoresis on serum and the 1.006 g/ml top and bottom preparative ultracentrifuge lipoprotein fractions. The latter was internally standardized by total lipid and plasma total cholesterol and triglyceride determinations giving normal reference lipoprotein values. The reading procedure allowed the identification and quantification of floating beta and sinking pre-beta. In the subpopulation, there were two of the former and 13 of the latter. For large scale clinical application of such quantitative lipoprotein electrophoresis full automation of the microdensitometry and calculations will be required."} {"id": "PMID:173964", "title": "Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: acute experiments in rats fed safflower oil.", "content": "Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.", "contents": "Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: acute experiments in rats fed safflower oil. Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver."} {"id": "PMID:173965", "title": "Synthesis of cholesterol esters in the plasma and liver of sheep.", "content": "A study was made with sheep on the formation in vitro of long chain fatty acid esters of cholesterol by the lecithin-cholesterol-acyltransferase system present in the plasma and the acyl CoA-cholesterola cyltransferase system present in the liver. The rate of cholesterol esterification in the plasma was 0.024 mumoles/ml/hr. The relative pattern of fatty acids esterified during incubation of the plasma remained constant over the 8 hr period of incubation and was similar to the fatty acids in the plasma cholesteryl esters before incubation began and to the fatty acids in the 2-position of the plasma lecithin. The predominant cholesteryl esters synthesized contained monoenoic and dienoic fatty acids. Unlike the bovine, there was no apparent discrimination in favor of the 18:2 containing species of plasma lecithin as donors of fatty acids. This difference could be accounted for by the similarity in the 18:2 content of the phospholipids present in the high density (density greater than 1.062 and less than 1.21) and the low density (density greater than 1.006 and less than 1.063) lipoprotein fractions of the sheep plasma. The possibility of some discrimination against 20:4 during cholesterol ester synthesis in the plasma of the sheep cannot be excluded. In the liver, the predominant cholesteryl esters synthesized contained saturated and monoenoic fatty acids; cholesteryl linoleate was synthesized to a very much less extent. There was considerable similarity between the composition of the unesterified fatty acid fraction of the liver before incubation began and the fatty acid composition of the cholesteryl esters synthesized during incubation. Addition of sonicated suspensions of free fatty acidsaltered markedly the fatty acid pattern of the cholesteryl esters synthesized by the liver slices. From the evidence presented it is concluded that the cholesteryl esters in sheep plasma are syntheized mainly by the plasma lecithin-cholesterol-acyltransferase system. The results are discussed in relation to cholesterol esterification systems demonstrated in the plasma and liver of monogastric animals.", "contents": "Synthesis of cholesterol esters in the plasma and liver of sheep. A study was made with sheep on the formation in vitro of long chain fatty acid esters of cholesterol by the lecithin-cholesterol-acyltransferase system present in the plasma and the acyl CoA-cholesterola cyltransferase system present in the liver. The rate of cholesterol esterification in the plasma was 0.024 mumoles/ml/hr. The relative pattern of fatty acids esterified during incubation of the plasma remained constant over the 8 hr period of incubation and was similar to the fatty acids in the plasma cholesteryl esters before incubation began and to the fatty acids in the 2-position of the plasma lecithin. The predominant cholesteryl esters synthesized contained monoenoic and dienoic fatty acids. Unlike the bovine, there was no apparent discrimination in favor of the 18:2 containing species of plasma lecithin as donors of fatty acids. This difference could be accounted for by the similarity in the 18:2 content of the phospholipids present in the high density (density greater than 1.062 and less than 1.21) and the low density (density greater than 1.006 and less than 1.063) lipoprotein fractions of the sheep plasma. The possibility of some discrimination against 20:4 during cholesterol ester synthesis in the plasma of the sheep cannot be excluded. In the liver, the predominant cholesteryl esters synthesized contained saturated and monoenoic fatty acids; cholesteryl linoleate was synthesized to a very much less extent. There was considerable similarity between the composition of the unesterified fatty acid fraction of the liver before incubation began and the fatty acid composition of the cholesteryl esters synthesized during incubation. Addition of sonicated suspensions of free fatty acidsaltered markedly the fatty acid pattern of the cholesteryl esters synthesized by the liver slices. From the evidence presented it is concluded that the cholesteryl esters in sheep plasma are syntheized mainly by the plasma lecithin-cholesterol-acyltransferase system. The results are discussed in relation to cholesterol esterification systems demonstrated in the plasma and liver of monogastric animals."} {"id": "PMID:173966", "title": "Viral stimulation of choline phosphotransferase in spleen microsomes.", "content": "Choline phosphotransferase and phosphatidyl ethanolamine methyltransferase enzymatic activities (nmoles phosphatidyl choline/min/mg protein) have been determined in spleen microsomes of Rauscher virus infected balb/c male mice at 5, 10, 14, and 21 days following inoculation of the virus. There is a significant stimulation of the choline phosphotransferase activity in the virus infected spleens with the peak of activity at about 10 days of viral infection. The specific activity of choline phosphotransferase is 10 times that of the phosphatidyl ethanolamine methyltransferase at 10 days of viral infection. There is a 51-fold increase over controls for the total microsomal choline phosphotransferase at 14 days of viral infection and only an 18-fold increase over controls for the phosphatidyl ethanolamine methyltransferase activity. There is a significant (P less than 0.001) increase over controls in the concentration of total phospholipid-P, phosphatidyl choline-P, and phosphatidyl choline-P fractions as separated by argentation chromatography of microsomes from spleens of mice infected with Friend virus of Rauscher virus for 14 days. The choline phosphotransferase and phosphatidyl ethanolamine methyltransferase specific activities in liver microsomes of 14 day Friend and/or Rauscher virus are unaltered during viral infection.", "contents": "Viral stimulation of choline phosphotransferase in spleen microsomes. Choline phosphotransferase and phosphatidyl ethanolamine methyltransferase enzymatic activities (nmoles phosphatidyl choline/min/mg protein) have been determined in spleen microsomes of Rauscher virus infected balb/c male mice at 5, 10, 14, and 21 days following inoculation of the virus. There is a significant stimulation of the choline phosphotransferase activity in the virus infected spleens with the peak of activity at about 10 days of viral infection. The specific activity of choline phosphotransferase is 10 times that of the phosphatidyl ethanolamine methyltransferase at 10 days of viral infection. There is a 51-fold increase over controls for the total microsomal choline phosphotransferase at 14 days of viral infection and only an 18-fold increase over controls for the phosphatidyl ethanolamine methyltransferase activity. There is a significant (P less than 0.001) increase over controls in the concentration of total phospholipid-P, phosphatidyl choline-P, and phosphatidyl choline-P fractions as separated by argentation chromatography of microsomes from spleens of mice infected with Friend virus of Rauscher virus for 14 days. The choline phosphotransferase and phosphatidyl ethanolamine methyltransferase specific activities in liver microsomes of 14 day Friend and/or Rauscher virus are unaltered during viral infection."} {"id": "PMID:173967", "title": "Effect of diet on fatty acids in the lipoprotein cholesteryl esters of type IIa and normal individuals.", "content": "Four normal and two individuals with type IIa hyperlipoproteinemia were placed on the National Heart and Lung Institute Type IIa Diet (less than 300 mg of cholesterol per day, high polyunsaturated, low saturated fat diet) for 1 week and on a normal diet the following week. Plasma samples were obtained and the cholesterol contents of plasma and of very low density, low density and high density lipoproteins determined. The cholesteryl esters in one type IIa and two normal individuals were identified. The cholesteryl esters in type IIa very low density lipoproteins from blood drawn 45 min after the last meal in each dietary period, contained less 18:2 than from the normal. After the first dietary period, the very low density lipoprotein cholesteryl ester 18:2 content for the type IIa was 37.2M% and for the normals, 54.7M%. After the second dietary period, the corresponding values were 49.7M% and 56.7M%. Fasting samples had lower 18:2 contents in the low density lipoproteins from the Type IIa subject following both dietary periods and in the high density lipoproteins following the Type II diet.", "contents": "Effect of diet on fatty acids in the lipoprotein cholesteryl esters of type IIa and normal individuals. Four normal and two individuals with type IIa hyperlipoproteinemia were placed on the National Heart and Lung Institute Type IIa Diet (less than 300 mg of cholesterol per day, high polyunsaturated, low saturated fat diet) for 1 week and on a normal diet the following week. Plasma samples were obtained and the cholesterol contents of plasma and of very low density, low density and high density lipoproteins determined. The cholesteryl esters in one type IIa and two normal individuals were identified. The cholesteryl esters in type IIa very low density lipoproteins from blood drawn 45 min after the last meal in each dietary period, contained less 18:2 than from the normal. After the first dietary period, the very low density lipoprotein cholesteryl ester 18:2 content for the type IIa was 37.2M% and for the normals, 54.7M%. After the second dietary period, the corresponding values were 49.7M% and 56.7M%. Fasting samples had lower 18:2 contents in the low density lipoproteins from the Type IIa subject following both dietary periods and in the high density lipoproteins following the Type II diet."} {"id": "PMID:173969", "title": "Adaptation of skeletal muscle to endurance exercise.", "content": "Skeletal muscle adapts to endurance excerise, such as long distance running, with an increase in the capacity for aerobic metabolism. This is reflected in an increased capacity of whole homogenates and of the mitochondrial fraction of muscle to oxidize pyruvate and long chain fatty acids. Underlying this increase in the ability to obtain energy by respiration is an increase in the levels of a number of mitochondrial enzymes. These include the enzymes involved in fatty acid oxidation, the enzymes of the citric acid cycle, the components of the respiratory chain that link the oxidation of succinate and NADH to oxygen, and coupling factor 1. These increases in mitochondrial enzyme activity appear to be due to an increase in enzyme protein as evidenced by a doubling of the concentration of cytochrome c and a 60% increase in the protein content of the mitochondrial fraction skeletal muscle. Electronmicroscopic studies suggest that increases in both the size and number of mitochondria are responsible for the increase in mitochondrial protein. An alteration in mitochondrial composition also occurs, with some mitochondrial enzymes increasing 2-fold, others increasing only 35% to 60%, while others, including mitochondrial alpha-glycerophosphate dehydrogenase, creatine phosphokinase and adenylate kinase do not increase at all. As a result of these and other exercise induced biochemical adaptations skeletal muscle tends to become more like heart muscle in its enzyme pattern.", "contents": "Adaptation of skeletal muscle to endurance exercise. Skeletal muscle adapts to endurance excerise, such as long distance running, with an increase in the capacity for aerobic metabolism. This is reflected in an increased capacity of whole homogenates and of the mitochondrial fraction of muscle to oxidize pyruvate and long chain fatty acids. Underlying this increase in the ability to obtain energy by respiration is an increase in the levels of a number of mitochondrial enzymes. These include the enzymes involved in fatty acid oxidation, the enzymes of the citric acid cycle, the components of the respiratory chain that link the oxidation of succinate and NADH to oxygen, and coupling factor 1. These increases in mitochondrial enzyme activity appear to be due to an increase in enzyme protein as evidenced by a doubling of the concentration of cytochrome c and a 60% increase in the protein content of the mitochondrial fraction skeletal muscle. Electronmicroscopic studies suggest that increases in both the size and number of mitochondria are responsible for the increase in mitochondrial protein. An alteration in mitochondrial composition also occurs, with some mitochondrial enzymes increasing 2-fold, others increasing only 35% to 60%, while others, including mitochondrial alpha-glycerophosphate dehydrogenase, creatine phosphokinase and adenylate kinase do not increase at all. As a result of these and other exercise induced biochemical adaptations skeletal muscle tends to become more like heart muscle in its enzyme pattern."} {"id": "PMID:173970", "title": "The influence of physical activity on ligaments and tendons.", "content": "Using either a bone-ligament-bone or a muscle-tendon-bone preparation, numerous investigators have demonstrated that the usual site of separation is in the transitional zone between the ligament (or tendon) and bone; hence, the term junction strength or load at separation is used to describe functional changes in these preparations. Junction strength is decreased with inactivity (immobilization) and increased with chronic activity (training) provided that the exercise program is of an endurance nature. Training also increases junction strength in thyroidectomized and hypophysectomized rats. Besides in junction strength, training results in heavier ligaments and higher ligament weight/length ratios. However, water content, collagen concentrations/dry weight or collagen concentration per weight/length unit are not significantly influenced by repeated bouts of exercise. Although immobilization is associated with lower elastic stiffness values (kg/mm), training appears to have little influence on this measure in normal animals. Rats and dogs with surgically repaired ligaments are weaker and the strength results are markedly lower if the leg is immobilized. Exercise training improves the repair strength of ligaments but does not result in normal values twelve weeks after the surgery. Exogenous administration of ICSH or testosterone results in higher repair strength whereas TSH, thyroxine, ACTH and growth hormone decreases this measure. It was concluded that the mechanical stress produced by chronic exercise is an important determination of the strength of repaired ligaments and of the junctions between ligaments (or tendons) and bones.", "contents": "The influence of physical activity on ligaments and tendons. Using either a bone-ligament-bone or a muscle-tendon-bone preparation, numerous investigators have demonstrated that the usual site of separation is in the transitional zone between the ligament (or tendon) and bone; hence, the term junction strength or load at separation is used to describe functional changes in these preparations. Junction strength is decreased with inactivity (immobilization) and increased with chronic activity (training) provided that the exercise program is of an endurance nature. Training also increases junction strength in thyroidectomized and hypophysectomized rats. Besides in junction strength, training results in heavier ligaments and higher ligament weight/length ratios. However, water content, collagen concentrations/dry weight or collagen concentration per weight/length unit are not significantly influenced by repeated bouts of exercise. Although immobilization is associated with lower elastic stiffness values (kg/mm), training appears to have little influence on this measure in normal animals. Rats and dogs with surgically repaired ligaments are weaker and the strength results are markedly lower if the leg is immobilized. Exercise training improves the repair strength of ligaments but does not result in normal values twelve weeks after the surgery. Exogenous administration of ICSH or testosterone results in higher repair strength whereas TSH, thyroxine, ACTH and growth hormone decreases this measure. It was concluded that the mechanical stress produced by chronic exercise is an important determination of the strength of repaired ligaments and of the junctions between ligaments (or tendons) and bones."} {"id": "PMID:173974", "title": "Glucocorticoid therapy.", "content": "1. There is a poor relationship between the circulating half-life a glucocorticoid and either its potency or its duration of action. Many actions of a glucocorticoid have unequal durations. The duration of action varies with the dose. 2. The presence of biological activity as a glucocorticoid depends on the presence of a hydroxyl group at carbon number 11. Cortisone and prednisone, which are 11-keto compounds, must be converted to 11-beta-hydroxyl compounds to be effective. This reaction may be impaired in the presence of liver disease. 3. Iatrogenic Cushing's syndrome differs from spontaneous Cushing's syndrome in several respects, possibly because in the former ACTH is suppressed but in Cushing's syndrome associated with bilateral adrenal hyperplasia ACTH levels are elevated...", "contents": "Glucocorticoid therapy. 1. There is a poor relationship between the circulating half-life a glucocorticoid and either its potency or its duration of action. Many actions of a glucocorticoid have unequal durations. The duration of action varies with the dose. 2. The presence of biological activity as a glucocorticoid depends on the presence of a hydroxyl group at carbon number 11. Cortisone and prednisone, which are 11-keto compounds, must be converted to 11-beta-hydroxyl compounds to be effective. This reaction may be impaired in the presence of liver disease. 3. Iatrogenic Cushing's syndrome differs from spontaneous Cushing's syndrome in several respects, possibly because in the former ACTH is suppressed but in Cushing's syndrome associated with bilateral adrenal hyperplasia ACTH levels are elevated..."} {"id": "PMID:173975", "title": "Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets.", "content": "Seven adults with familial hypophosphatemia have been investigated by histologic and radiographic examination of bone, and estimates of bone mineral status by in vivo neutron activation analysis (IVNAA). Histological examination showed severe osteomalacia and osteosclerosis in all cases. Radiography showed skeletal deformities and other sequelae of severe rickets of childhood in five of the seven cases, with, in addition, thickened well-mineralized bones; the other two showed normal radiographs. IVNAA measurements showed that the first five had greater than normal bone calcium and that the other two had normal values. Thus, in all cases there is a greater than normal total bone tissue (osteoid and mineralized bone together). The quantitative body calcium measurements show clearly that osteosclerosis occurs in familial hypophosphatemia, confirming the opinions based on histological and radiological data. Although there has been occasional reference to this sclerosis in the literature, up to the present it has received little attention.", "contents": "Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets. Seven adults with familial hypophosphatemia have been investigated by histologic and radiographic examination of bone, and estimates of bone mineral status by in vivo neutron activation analysis (IVNAA). Histological examination showed severe osteomalacia and osteosclerosis in all cases. Radiography showed skeletal deformities and other sequelae of severe rickets of childhood in five of the seven cases, with, in addition, thickened well-mineralized bones; the other two showed normal radiographs. IVNAA measurements showed that the first five had greater than normal bone calcium and that the other two had normal values. Thus, in all cases there is a greater than normal total bone tissue (osteoid and mineralized bone together). The quantitative body calcium measurements show clearly that osteosclerosis occurs in familial hypophosphatemia, confirming the opinions based on histological and radiological data. Although there has been occasional reference to this sclerosis in the literature, up to the present it has received little attention."} {"id": "PMID:173976", "title": "Effects of reduced ATP concent on hepatic responses to glucagon.", "content": "Expression of the glycogenolytic action of glucagon in liver requires ATP for cAMP formation and for several subsequent phosphorylation reactions. To assess the extent to which ATP availability is rate-limiting to this hormonal action, responses to glucagon of intact liver and of liver with marked reductions in ATP content induced by ethionine was examined in female Wistar rats in vivo and in vitro. Compared to values in quick-frozen liver samples from control rats, basal hepatic ATP was 75% lower and cAMP, two fold higher in rats treated with ethionine. Activation of glycogen phosphorylase and inactivation of glycogen synthetase, phosphorylation reactions which require ATP and are initiated by cAMP, were also evident in basal liver samples from ethionine-treated rats. These hepatic alterations were associated with portal glucose and insulin levels which were significantly lower and portal glucagon levels which were four fold higher than values in controls. In ethionine-treated rats, glucose infusion decreased hepatic cAMP content and phosphorylase activity and increased synthetase activity. This and other observation suggested that the higher cAMP and the altered enzyme activities seen in vivo after ethionine administration were mediated by the hyperglucagonemia and/or by other endogenous glycogenolytic stimuli, and accordingly implied that liver remained responsive to such stimuli despite reduced ATP. Pharmacologic doses of exogenous glucagon clearly increased cAMP in vivo and in vitro in livers with decreased ATP. However, the lower ATP of liver exposed to ethionine was associated with a significantly blunted cAMP response to maximal glucagon stimulation. By contrast, alterations in phosphorylase and synthetase activities were not similarly blunted, suggesting that the smaller increases in cAMP seen in liver with reduced ATP content were adequate for the expression of these actions of the hormone. It is concluded that the actions of glucagon to increase cAMP and to activate phosphorylase and inactivate synthetase are not abolished by marked reductions in hepatic APT.", "contents": "Effects of reduced ATP concent on hepatic responses to glucagon. Expression of the glycogenolytic action of glucagon in liver requires ATP for cAMP formation and for several subsequent phosphorylation reactions. To assess the extent to which ATP availability is rate-limiting to this hormonal action, responses to glucagon of intact liver and of liver with marked reductions in ATP content induced by ethionine was examined in female Wistar rats in vivo and in vitro. Compared to values in quick-frozen liver samples from control rats, basal hepatic ATP was 75% lower and cAMP, two fold higher in rats treated with ethionine. Activation of glycogen phosphorylase and inactivation of glycogen synthetase, phosphorylation reactions which require ATP and are initiated by cAMP, were also evident in basal liver samples from ethionine-treated rats. These hepatic alterations were associated with portal glucose and insulin levels which were significantly lower and portal glucagon levels which were four fold higher than values in controls. In ethionine-treated rats, glucose infusion decreased hepatic cAMP content and phosphorylase activity and increased synthetase activity. This and other observation suggested that the higher cAMP and the altered enzyme activities seen in vivo after ethionine administration were mediated by the hyperglucagonemia and/or by other endogenous glycogenolytic stimuli, and accordingly implied that liver remained responsive to such stimuli despite reduced ATP. Pharmacologic doses of exogenous glucagon clearly increased cAMP in vivo and in vitro in livers with decreased ATP. However, the lower ATP of liver exposed to ethionine was associated with a significantly blunted cAMP response to maximal glucagon stimulation. By contrast, alterations in phosphorylase and synthetase activities were not similarly blunted, suggesting that the smaller increases in cAMP seen in liver with reduced ATP content were adequate for the expression of these actions of the hormone. It is concluded that the actions of glucagon to increase cAMP and to activate phosphorylase and inactivate synthetase are not abolished by marked reductions in hepatic APT."} {"id": "PMID:173977", "title": "[Change in the activity of the enzymatic systems of Bacillus anthracoides spores during germination and under the action of Ca hypochlorite].", "content": "The activity of the enzymes of the citric acid cycle, glycolysis, and hexose monophosphate pathway was studied during germination of the spores of Bacillus anthracoides and upon their treatment with calcium hypochlorite. No activity of isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase was found in the extracts of the vegetative cells, contrary to the spores and initiated spores. The activity of other enzymes changes but slightly in the course of germination of the spores. Treatment of the spores with calcium hypochlorite inhibited their initiation and germination and the activity of several enzymes, especially malate dehydrogenase, isocitrate dehydrogenase, and fumarase.", "contents": "[Change in the activity of the enzymatic systems of Bacillus anthracoides spores during germination and under the action of Ca hypochlorite]. The activity of the enzymes of the citric acid cycle, glycolysis, and hexose monophosphate pathway was studied during germination of the spores of Bacillus anthracoides and upon their treatment with calcium hypochlorite. No activity of isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase was found in the extracts of the vegetative cells, contrary to the spores and initiated spores. The activity of other enzymes changes but slightly in the course of germination of the spores. Treatment of the spores with calcium hypochlorite inhibited their initiation and germination and the activity of several enzymes, especially malate dehydrogenase, isocitrate dehydrogenase, and fumarase."} {"id": "PMID:173978", "title": "[Inorganic pyrophosphate synthesis by the mitochondria of the yeast-like fungus Endomyces magnusii coupled with the work of the respiratory chain].", "content": "The synthesis of inorganic pyrophosphate by the mitochondria of Endomyces magnusii was found to be coupled with respiration. The mitochondria of E. magnusii can utilize the energy of the phosphoanhydride bond of inorganic pyrophosphate for the synthesis of ATP. The study with inhibitors suggests the participation of inorganic pyrophosphatase and ATPase in this process.", "contents": "[Inorganic pyrophosphate synthesis by the mitochondria of the yeast-like fungus Endomyces magnusii coupled with the work of the respiratory chain]. The synthesis of inorganic pyrophosphate by the mitochondria of Endomyces magnusii was found to be coupled with respiration. The mitochondria of E. magnusii can utilize the energy of the phosphoanhydride bond of inorganic pyrophosphate for the synthesis of ATP. The study with inhibitors suggests the participation of inorganic pyrophosphatase and ATPase in this process."} {"id": "PMID:173986", "title": "[Dynamics of plasma corticoid levels following intranuscular or intravenous ACTH-stimulation in children and adults (author's transl)].", "content": "Following ACTH-stimulation, in 40 patients plasma corticoid levels (CPB-technique) were determined every 15 min for three hours to demonstrate the period of maximal increase. There was no significant difference in the increase of plasma cortisol following intravenous or intramuscular injection of ACTH (beta1-23). Peak values were reached at 60 min (65.2 +/- 3.2 mug/100 ml). This is considered to be the right moment for blood sampling when using a short ACTH-test.", "contents": "[Dynamics of plasma corticoid levels following intranuscular or intravenous ACTH-stimulation in children and adults (author's transl)]. Following ACTH-stimulation, in 40 patients plasma corticoid levels (CPB-technique) were determined every 15 min for three hours to demonstrate the period of maximal increase. There was no significant difference in the increase of plasma cortisol following intravenous or intramuscular injection of ACTH (beta1-23). Peak values were reached at 60 min (65.2 +/- 3.2 mug/100 ml). This is considered to be the right moment for blood sampling when using a short ACTH-test."} {"id": "PMID:173987", "title": "[Morphology and incidence of membranous structures related to endoplasmic reticulum].", "content": "Morphology and occurrence of so called tubuloreticular (TRS) and undulating membraneous structures (UMS) connected with the membranes of the endoplasmatic reticulum are described in physiological and pathological conditions. It is established that TRS and UMS represent a cytoplasmatic inclusion of similar type, although of different structures. Occurrence of UMS in human lung-tissue culture, and in transplantable chicken hepatoma induced in a hepatic tumour by MC-29 virus was observed.", "contents": "[Morphology and incidence of membranous structures related to endoplasmic reticulum]. Morphology and occurrence of so called tubuloreticular (TRS) and undulating membraneous structures (UMS) connected with the membranes of the endoplasmatic reticulum are described in physiological and pathological conditions. It is established that TRS and UMS represent a cytoplasmatic inclusion of similar type, although of different structures. Occurrence of UMS in human lung-tissue culture, and in transplantable chicken hepatoma induced in a hepatic tumour by MC-29 virus was observed."} {"id": "PMID:173988", "title": "[Ultrastructure and hormone secretion of a tissue culture from an adrenal gland tumor simulating Cushing's syndrome].", "content": "Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipidrich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production.", "contents": "[Ultrastructure and hormone secretion of a tissue culture from an adrenal gland tumor simulating Cushing's syndrome]. Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipidrich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production."} {"id": "PMID:173989", "title": "[Clinical aspects of intrauterine infections (author's transl)].", "content": "Examples of typical embryopathy (rubella, cytomegaly) and fetopathy (toxoplasmosis, listeriosis) demonstrate the disastrous effects intrauterine infections may have on the fetus. Even if they play a relatively small role numerically, they deserve our particular attention because we feel and hope that, by extending maternity care to environmental hygiene and prophylactic vaccination, they can be partly prevented and, by improving prenatal serological diagnosis and intensifying the cooperation of specialists, introduced early to an effective prenatal therapy, thus preventing severe damage to the child.", "contents": "[Clinical aspects of intrauterine infections (author's transl)]. Examples of typical embryopathy (rubella, cytomegaly) and fetopathy (toxoplasmosis, listeriosis) demonstrate the disastrous effects intrauterine infections may have on the fetus. Even if they play a relatively small role numerically, they deserve our particular attention because we feel and hope that, by extending maternity care to environmental hygiene and prophylactic vaccination, they can be partly prevented and, by improving prenatal serological diagnosis and intensifying the cooperation of specialists, introduced early to an effective prenatal therapy, thus preventing severe damage to the child."} {"id": "PMID:173990", "title": "[Diagnostic possibilities for the prevention and identification of intrauterine infections (author's transl)].", "content": "The demonstration of antibody titer movements in the hemagglutination inhibition test, in the complement fixation test and a differentiation between IgM and IgG antibodies allow information to be obtained on the age of an intra-uterine rubella infection. Specific IgM antibodies in neonates are reliable evidence, because the maternal IgM antibodies cannot cross the placenta. A rise in total IgM level in cord blood does not, on the other hand, indicate an embryopathy in every case. In contradistinction to rubella, cytomegaly and herpes simplex virus can be comparatively easily and quickly cultivated, so that identification of the virus is of use for clinical purposes. Of 2360 children investigated in our laboratory from 1969-1974, 120 certainly and 57 extremely probably showed rubella embryopathies.", "contents": "[Diagnostic possibilities for the prevention and identification of intrauterine infections (author's transl)]. The demonstration of antibody titer movements in the hemagglutination inhibition test, in the complement fixation test and a differentiation between IgM and IgG antibodies allow information to be obtained on the age of an intra-uterine rubella infection. Specific IgM antibodies in neonates are reliable evidence, because the maternal IgM antibodies cannot cross the placenta. A rise in total IgM level in cord blood does not, on the other hand, indicate an embryopathy in every case. In contradistinction to rubella, cytomegaly and herpes simplex virus can be comparatively easily and quickly cultivated, so that identification of the virus is of use for clinical purposes. Of 2360 children investigated in our laboratory from 1969-1974, 120 certainly and 57 extremely probably showed rubella embryopathies."} {"id": "PMID:173992", "title": "Basis for recurring ventricular fibrillation in the absence of coronary heart disease and its management.", "content": "A 39-year-old man twice experienced ventricular fibrillation and exhibited numerous ventricular premature beats. Coronary arteries were normal, and no impaired cardiac function was found upon catheterization. Evidence was adduced that the ventricular premature beats were related to higher nervous activity. The patient had serious psychiatric problems; the ventricular premature beats were provoked by psychophysiologic stress, increased during REM sleep, were reduced by meditation, and were controlled by beta-adrenergic blockade, phenytoin and digitalization. We conclude that psychologic and neurophysiologic factors may predispose to life-threatening cardiac arrhythmia in the absence of organic heart disease. Effective management of the recurrent ventricular arrhythmia involved; acute drug testing for assessing antiarrhythmic efficacy; use of programmed trendscription to provide on-line information on drug action; a treatment program involving more than one agent; and use of measures to reduce sympathetic nervous activity.", "contents": "Basis for recurring ventricular fibrillation in the absence of coronary heart disease and its management. A 39-year-old man twice experienced ventricular fibrillation and exhibited numerous ventricular premature beats. Coronary arteries were normal, and no impaired cardiac function was found upon catheterization. Evidence was adduced that the ventricular premature beats were related to higher nervous activity. The patient had serious psychiatric problems; the ventricular premature beats were provoked by psychophysiologic stress, increased during REM sleep, were reduced by meditation, and were controlled by beta-adrenergic blockade, phenytoin and digitalization. We conclude that psychologic and neurophysiologic factors may predispose to life-threatening cardiac arrhythmia in the absence of organic heart disease. Effective management of the recurrent ventricular arrhythmia involved; acute drug testing for assessing antiarrhythmic efficacy; use of programmed trendscription to provide on-line information on drug action; a treatment program involving more than one agent; and use of measures to reduce sympathetic nervous activity."} {"id": "PMID:173994", "title": "Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men.", "content": "To ascertain the frequency of defined hyperlipoproteinemia and to investigate the relation between lipoprotein fractions and coronary heart disease, we measured serum lipoprotein cholesterol levels in a population-based sample of Hawaii Japanese men 50 to 72 years old. Type II hyperlipoproteinemia was present in 3 per cent of 1859 men, and Type IV in 26 per cent. Relative risks for coronary heart disease, based on 264 prevalence cases, were found to be 1.8, 1.8 and 0.46, between the upper and lower quartiles of total, beta, and alpha cholesterol, respectively. We found no significant relation between triglyceride and coronary heart disease. The inverse relation of alpha cholesterol of prevalence of coronary heart disease was independent of beta cholesterol, obesity, and other factors. The data suggest the need for further evaluation of the protective effect of the alpha lipoprotein fraction on the development of coronary heart disease.", "contents": "Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. To ascertain the frequency of defined hyperlipoproteinemia and to investigate the relation between lipoprotein fractions and coronary heart disease, we measured serum lipoprotein cholesterol levels in a population-based sample of Hawaii Japanese men 50 to 72 years old. Type II hyperlipoproteinemia was present in 3 per cent of 1859 men, and Type IV in 26 per cent. Relative risks for coronary heart disease, based on 264 prevalence cases, were found to be 1.8, 1.8 and 0.46, between the upper and lower quartiles of total, beta, and alpha cholesterol, respectively. We found no significant relation between triglyceride and coronary heart disease. The inverse relation of alpha cholesterol of prevalence of coronary heart disease was independent of beta cholesterol, obesity, and other factors. The data suggest the need for further evaluation of the protective effect of the alpha lipoprotein fraction on the development of coronary heart disease."} {"id": "PMID:173995", "title": "Respiratory syncytial virus infections within families.", "content": "To examine intrafamily spread of respiratory syncytial virus infections and their associated illnesses, 36 families with 188 members were studied during an outbreak of such infections. Nurses visited every three to four days to obtain specimens for viral isolation and interview household members. The virus infected 44.4 per cent of families, and 21.9 per cent of all members. All age groups had appreciable attack rates (with a range of 16.8 per cent in adults to 29.4 per cent in infants). In infected families, 45.9 per cent of members became infected, including 10 of 16 infants. Secondary attack rate for all ages was 27 per cent, and that for infants 45.4 per cent. An infant's older sibling appeared most likely to introduce the virus into the family. Associated acute respiratory illnesses occurred in 94.9 per cent of cases, and appeared more severe than those not associated with respiratory syncytial virus. When the virus was introduced into a family the high attack rate produced an illness of age-related severity.", "contents": "Respiratory syncytial virus infections within families. To examine intrafamily spread of respiratory syncytial virus infections and their associated illnesses, 36 families with 188 members were studied during an outbreak of such infections. Nurses visited every three to four days to obtain specimens for viral isolation and interview household members. The virus infected 44.4 per cent of families, and 21.9 per cent of all members. All age groups had appreciable attack rates (with a range of 16.8 per cent in adults to 29.4 per cent in infants). In infected families, 45.9 per cent of members became infected, including 10 of 16 infants. Secondary attack rate for all ages was 27 per cent, and that for infants 45.4 per cent. An infant's older sibling appeared most likely to introduce the virus into the family. Associated acute respiratory illnesses occurred in 94.9 per cent of cases, and appeared more severe than those not associated with respiratory syncytial virus. When the virus was introduced into a family the high attack rate produced an illness of age-related severity."} {"id": "PMID:173996", "title": "Liver-cell adenomas associated with use of oral contraceptives.", "content": "During the past six years an increasing number of liver-cell adenomas in women were diagnosed, and we undertook a study of possible etiologic factors, including use of oral contraceptives, in 42 women. There was a significant difference between cases and matched controls in mean months of oral-contraceptive use: 73.4 as compared to 36.2 (P less than 0.001). The women with adenomas took mestranol-containing pills much more commonly than the controls (P less than 0.0001). Hemorrhage into the tumor was often associated with the onset of menstruation in women taking oral contraceptives. Long-term use of oral contraceptives, especially those containing a high total dose of steroids or mestranol as the synthetic estrogen, should be balanced against risks of side effects of the drugs.", "contents": "Liver-cell adenomas associated with use of oral contraceptives. During the past six years an increasing number of liver-cell adenomas in women were diagnosed, and we undertook a study of possible etiologic factors, including use of oral contraceptives, in 42 women. There was a significant difference between cases and matched controls in mean months of oral-contraceptive use: 73.4 as compared to 36.2 (P less than 0.001). The women with adenomas took mestranol-containing pills much more commonly than the controls (P less than 0.0001). Hemorrhage into the tumor was often associated with the onset of menstruation in women taking oral contraceptives. Long-term use of oral contraceptives, especially those containing a high total dose of steroids or mestranol as the synthetic estrogen, should be balanced against risks of side effects of the drugs."} {"id": "PMID:174008", "title": "[Lacrimators as acceptors for NADH].", "content": "Lachrymators of varied structure are reduced either by hydrogen addition or halogen substitution using NADH model compounds as donors. Similar compounds without lachrymatory activity were reduced either very slowly or not at all. CS (o-Chlorobenzalmalonitril) is reduced by NADH, the reaction being catalyzed by an enzyme present in erythrocytes. Thus the lachrymatory action follows a general scheme for the activity of sensory transduction. This scheme consists of a reception in the nerve cell membrane and a fast or simultaneous chemical transformation in an enzymic reaction.", "contents": "[Lacrimators as acceptors for NADH]. Lachrymators of varied structure are reduced either by hydrogen addition or halogen substitution using NADH model compounds as donors. Similar compounds without lachrymatory activity were reduced either very slowly or not at all. CS (o-Chlorobenzalmalonitril) is reduced by NADH, the reaction being catalyzed by an enzyme present in erythrocytes. Thus the lachrymatory action follows a general scheme for the activity of sensory transduction. This scheme consists of a reception in the nerve cell membrane and a fast or simultaneous chemical transformation in an enzymic reaction."} {"id": "PMID:174009", "title": "Outbreaks of swine vesicular disease in japan: virus isolation and epizootiological survey.", "content": "Outbreaks of a vesicular disease occurred among pigs in Kanagawa and Ibaraki Prefectures in Japan in November, 1973. Another outbreak was observed in Aichi Prefecture in December. The clinical signs of the disease observed included fever and vesicular lesions on the coronary bands, bulbs of the heel and in the interdigital spaces. In some pigs, vesicular lesions were observed on the snout, tongue and skin overlying the legs and abdomen. All the vesicular samples produced cytopathic changes on cultures of primary swine kidney cells of PK-15 cells. Three isolates of cytopathic agents tested were identified as swine vesicular disease virus from their physicochemical properties and antigenicity. The virus strains isolated from vesicular epithelial samples obtained from Ibaraki, Kanagawa and Aichi Prefectures were designated as Japan/Ibaraki/1/73, Japan/Kanagawa/1/73 and Japan/Aichi/1/73 strain, respectively. An outbreak of the disease among pigs due to swine vesicular disease virus was confirmed by the serum neutralization test with serum samples collected from pigs on affected farms. Approximately 80% of the pigs housed in affected shed showed high levels of neutralizing antibody titers. This is the first to report an occurrence of swine vesicular disease among pigs in Japan.", "contents": "Outbreaks of swine vesicular disease in japan: virus isolation and epizootiological survey. Outbreaks of a vesicular disease occurred among pigs in Kanagawa and Ibaraki Prefectures in Japan in November, 1973. Another outbreak was observed in Aichi Prefecture in December. The clinical signs of the disease observed included fever and vesicular lesions on the coronary bands, bulbs of the heel and in the interdigital spaces. In some pigs, vesicular lesions were observed on the snout, tongue and skin overlying the legs and abdomen. All the vesicular samples produced cytopathic changes on cultures of primary swine kidney cells of PK-15 cells. Three isolates of cytopathic agents tested were identified as swine vesicular disease virus from their physicochemical properties and antigenicity. The virus strains isolated from vesicular epithelial samples obtained from Ibaraki, Kanagawa and Aichi Prefectures were designated as Japan/Ibaraki/1/73, Japan/Kanagawa/1/73 and Japan/Aichi/1/73 strain, respectively. An outbreak of the disease among pigs due to swine vesicular disease virus was confirmed by the serum neutralization test with serum samples collected from pigs on affected farms. Approximately 80% of the pigs housed in affected shed showed high levels of neutralizing antibody titers. This is the first to report an occurrence of swine vesicular disease among pigs in Japan."} {"id": "PMID:174010", "title": "Diagnosis of bovine respiratory syncytial virus infection by complement fixation test.", "content": "The complement fixation test by the microtiter method was applied to the serological diagnosis of bovine respiratory syncytial (RS) virus infection. When used as complement fixing antigens, untreated infected cell culture fluid, fluorocarbon-treated, and ether-treated materials showed no differences in antigenicity among them. The complement fixing antigenicity of bovine RS virus appeared in bovine kidney and Vero cell cultures for the first time 4 days after inoculation. Both the infectivity and complement fixing antigenicity reached a maximum 6 days after inoculation. In detecting complement fixing antibody from infected cattle, the most outstanding specific reaction was obtained when 5% fresh normal calf serum had been added to the diluent of complement. Neutralizing and complement fixing antibodies were examined in serum samples from two cattle in the course of experimental infection. It was found that both antibodies turned to be positive 2 weeks after inoculation. There was a linear correlation between neutralizing and complement fixing antibody titers, when serum samples from 40 natural cases were tested in the acute and convalescent stages. In addition, common antigenicity was demonstrated between the virus of bovine origin and the Long strain of human RS virus by complement fixation test.", "contents": "Diagnosis of bovine respiratory syncytial virus infection by complement fixation test. The complement fixation test by the microtiter method was applied to the serological diagnosis of bovine respiratory syncytial (RS) virus infection. When used as complement fixing antigens, untreated infected cell culture fluid, fluorocarbon-treated, and ether-treated materials showed no differences in antigenicity among them. The complement fixing antigenicity of bovine RS virus appeared in bovine kidney and Vero cell cultures for the first time 4 days after inoculation. Both the infectivity and complement fixing antigenicity reached a maximum 6 days after inoculation. In detecting complement fixing antibody from infected cattle, the most outstanding specific reaction was obtained when 5% fresh normal calf serum had been added to the diluent of complement. Neutralizing and complement fixing antibodies were examined in serum samples from two cattle in the course of experimental infection. It was found that both antibodies turned to be positive 2 weeks after inoculation. There was a linear correlation between neutralizing and complement fixing antibody titers, when serum samples from 40 natural cases were tested in the acute and convalescent stages. In addition, common antigenicity was demonstrated between the virus of bovine origin and the Long strain of human RS virus by complement fixation test."} {"id": "PMID:174013", "title": "[Cholinergic mechanisms of interneuronal transmission in the retina].", "content": "Acetylcholine applied to the isolated perfused retina (frog and man) elicits a slow corneapositive potential. Such an effect of ACh besides the data known from the literature confirms an assumption on cholinergic synaptic transmission within the retina. The retinal potential elicited by ACh depends in its size and time course on definite parameters of the ACh application as well as on the illumination state of the retina: light stimulation diminishes the electrogenic action of ACh, flickering illumination being more effective than steady one. On the other hand electrical responsiveness of the retina to light lowered during the perfusion of the preparation with ACh. The b-wave seems to be the most sensitive part of the ERG and can be abolished completely, thus isolating the component PIII. The mentioned results as well as the data from the literature indicate the synapses between the first and second retinal neurons as the points of ACh action. Experimental results can be interpreted as the consequence of a desensitization of the cholinergic receptors within the retina.", "contents": "[Cholinergic mechanisms of interneuronal transmission in the retina]. Acetylcholine applied to the isolated perfused retina (frog and man) elicits a slow corneapositive potential. Such an effect of ACh besides the data known from the literature confirms an assumption on cholinergic synaptic transmission within the retina. The retinal potential elicited by ACh depends in its size and time course on definite parameters of the ACh application as well as on the illumination state of the retina: light stimulation diminishes the electrogenic action of ACh, flickering illumination being more effective than steady one. On the other hand electrical responsiveness of the retina to light lowered during the perfusion of the preparation with ACh. The b-wave seems to be the most sensitive part of the ERG and can be abolished completely, thus isolating the component PIII. The mentioned results as well as the data from the literature indicate the synapses between the first and second retinal neurons as the points of ACh action. Experimental results can be interpreted as the consequence of a desensitization of the cholinergic receptors within the retina."} {"id": "PMID:174014", "title": "[Synaptic processes in neurons of the cat pericruciate cortex evoked by pyramidal tract stimulation].", "content": "The influences of pyramidal tract stimulation on the activity of neurons in the pericruciate cortex were investigated on 423 neurons (81 neurons were studied intracellularly and 342--extracellularly), 78 of them having background activity. Pyramidal stimulation is shown to evoke not only antidromic spikes (0.5-16.0 ms latency) in the pyramidal cells, but also lateral and recurrent PSPs in the pyramidal and unidentified units of all cortical layers. IPSPs were observed in 46.7% of the investigated neurons, EPSPs--in 21.0%, mixed responces--in 26.0%. The latency of IPSPs was 1.5-14.0 ms, their amplitude ranged from 1.3 to 17.0 mV, the duration of the rising phase varied from 4 to 18 ms and the whole duration was 18-120 ms reaching sometimes 250-500 ms. In 30% of cases it was possible to divide the IPSPs into two phases: a fast one with a duration of 10-20 ms and a slow one. The latency of IPSPs was 2.6-19.0 ms, their amplitude--1.0--7.8 mV and duration--from 10.0 to 50.0 ms. The antidromic discharge in the pyramidal tract inhibited the background activity for 200-400 ms in 51.2% of spontaneously active units; acceleration was observed in 19.5% and mixed effect in 7.4% of units. The participation of pyramidal axonal collaterals and cortical interneurons in generation of the described processes is discussed.", "contents": "[Synaptic processes in neurons of the cat pericruciate cortex evoked by pyramidal tract stimulation]. The influences of pyramidal tract stimulation on the activity of neurons in the pericruciate cortex were investigated on 423 neurons (81 neurons were studied intracellularly and 342--extracellularly), 78 of them having background activity. Pyramidal stimulation is shown to evoke not only antidromic spikes (0.5-16.0 ms latency) in the pyramidal cells, but also lateral and recurrent PSPs in the pyramidal and unidentified units of all cortical layers. IPSPs were observed in 46.7% of the investigated neurons, EPSPs--in 21.0%, mixed responces--in 26.0%. The latency of IPSPs was 1.5-14.0 ms, their amplitude ranged from 1.3 to 17.0 mV, the duration of the rising phase varied from 4 to 18 ms and the whole duration was 18-120 ms reaching sometimes 250-500 ms. In 30% of cases it was possible to divide the IPSPs into two phases: a fast one with a duration of 10-20 ms and a slow one. The latency of IPSPs was 2.6-19.0 ms, their amplitude--1.0--7.8 mV and duration--from 10.0 to 50.0 ms. The antidromic discharge in the pyramidal tract inhibited the background activity for 200-400 ms in 51.2% of spontaneously active units; acceleration was observed in 19.5% and mixed effect in 7.4% of units. The participation of pyramidal axonal collaterals and cortical interneurons in generation of the described processes is discussed."} {"id": "PMID:174015", "title": "[Generation and propagation of direct responses of intact and chronically isolated strips of cortex].", "content": "Generation and transmission mechanisms of direct cortical responses were studied in the acute experiment on unanesthetized curarized cats ant intact cortex or a chronically isolated cortical strip. All studied properties of the direct response at the intact cortex and isolated strip of gyrus suprasilvius are identical. The blockage of cortical muscarinic cholinoreceptors between the stimulating and recording electrodes prevents or significantly decreases excitation transmission throught his part of the cortex. This can be explained by a polysynaptic mechanism of the response transmission. Neuronal nets providing the propagation of direct responses are anisotropic. Both normal and inverted (by GABA, nembutal or coagulation of the cortical surface) direct responses are increased aiter anticholinesterase drug (galanthamine) application. Amizil abolishes all these potential. A suggestion is made that both deep and superficial components of the direct cortical response are generated by endogenous cortical cholinergic elements.", "contents": "[Generation and propagation of direct responses of intact and chronically isolated strips of cortex]. Generation and transmission mechanisms of direct cortical responses were studied in the acute experiment on unanesthetized curarized cats ant intact cortex or a chronically isolated cortical strip. All studied properties of the direct response at the intact cortex and isolated strip of gyrus suprasilvius are identical. The blockage of cortical muscarinic cholinoreceptors between the stimulating and recording electrodes prevents or significantly decreases excitation transmission throught his part of the cortex. This can be explained by a polysynaptic mechanism of the response transmission. Neuronal nets providing the propagation of direct responses are anisotropic. Both normal and inverted (by GABA, nembutal or coagulation of the cortical surface) direct responses are increased aiter anticholinesterase drug (galanthamine) application. Amizil abolishes all these potential. A suggestion is made that both deep and superficial components of the direct cortical response are generated by endogenous cortical cholinergic elements."} {"id": "PMID:174016", "title": "[Postsynaptic membrane sensitivity to acetylcholine during blockade of excitatory transmission from nerve to skeletal muscle during long-term low-frequency transmission].", "content": "Blocking of myoneural transmission resulting from indirect low-frequency stimulation (fatigue) was not followed by amplitude changes in miniature end-plate potentials and acetylcholine-potentials. A conclusion was drawn that in performed experiments the acetylcholine sensitivity of the postsynaptic membrane was not changed and the decrease of endplate potentials amplitude during fatigue was due to the lowering of EPPs quantum content. A reduction in the quantum content of EPP results from negative antidromic influence of the muscle on the motor nerve endings caused by chemical agents formed in muscle during its contractile appartus activity.", "contents": "[Postsynaptic membrane sensitivity to acetylcholine during blockade of excitatory transmission from nerve to skeletal muscle during long-term low-frequency transmission]. Blocking of myoneural transmission resulting from indirect low-frequency stimulation (fatigue) was not followed by amplitude changes in miniature end-plate potentials and acetylcholine-potentials. A conclusion was drawn that in performed experiments the acetylcholine sensitivity of the postsynaptic membrane was not changed and the decrease of endplate potentials amplitude during fatigue was due to the lowering of EPPs quantum content. A reduction in the quantum content of EPP results from negative antidromic influence of the muscle on the motor nerve endings caused by chemical agents formed in muscle during its contractile appartus activity."} {"id": "PMID:174020", "title": "Incorporation of [3H] leucine into brain stem protein fractions: the effect of a behaviorally active, N-terminal fragment of ACTH in hypophysectomized rats.", "content": "In hypophysectomized rats, the incorporation of [3H] leucine into rat brain stem protein, measured 5 min after injection of the precursor into the diencephalon, was decreased. Chronic treatment of these rats with the N-terminal fragment of ACTH, ACTH1-10 increased the incorporation rate. Brain stem proteins were sequentially extracted with a hypotonic buffer, Triton X-100 and SDS. Analysis of these protein fractions on polyacrylamide gels revealed that hypophysectomy caused a general decrease in leucine incorporation into all protein species studied, whereas treatment of hypophysectomized rats with ACTH1-10 enhanced this incororation into all proteins. Superimposed on these general effects were minor differences found in two protein bands. Thus, removal of the pituitary and subsequent, chronic treatment of rats with ACTH1-10 interferes with overall protein metabolism rather than with certain protein species in particular.", "contents": "Incorporation of [3H] leucine into brain stem protein fractions: the effect of a behaviorally active, N-terminal fragment of ACTH in hypophysectomized rats. In hypophysectomized rats, the incorporation of [3H] leucine into rat brain stem protein, measured 5 min after injection of the precursor into the diencephalon, was decreased. Chronic treatment of these rats with the N-terminal fragment of ACTH, ACTH1-10 increased the incorporation rate. Brain stem proteins were sequentially extracted with a hypotonic buffer, Triton X-100 and SDS. Analysis of these protein fractions on polyacrylamide gels revealed that hypophysectomy caused a general decrease in leucine incorporation into all protein species studied, whereas treatment of hypophysectomized rats with ACTH1-10 enhanced this incororation into all proteins. Superimposed on these general effects were minor differences found in two protein bands. Thus, removal of the pituitary and subsequent, chronic treatment of rats with ACTH1-10 interferes with overall protein metabolism rather than with certain protein species in particular."} {"id": "PMID:174021", "title": "[Clinical value of magnification cerebral angiography (author's transl)].", "content": "Magnification carotid and vertebral angiography was performed via femoral catheter with magnification factor of 2.5 to 3.0, utilizing 0.1 X 0.1 ultra fine focal spot, manufactured by Shimadzu Seisakusho, Ltd. The standard angiograms were compared with magnification angiograms in a group of 67 patients with brain tumors and vascular disorders. The magnification angiography was more valuable than conventional angiography in 12 of 17 vascular tumors, while it was rarely valuable for diagnosis of vascular tumors. Aneurysms, occlusive diseases, collateral vessels, and capillary blush were also visualized to better advantage on magnification angiograms. Magnification cerebral angiography is a useful tool for elucidating small vascular branches, but further refinement in the design of focal spots and angiographic techinques is required for further improvement of magnification cerebral angiography.", "contents": "[Clinical value of magnification cerebral angiography (author's transl)]. Magnification carotid and vertebral angiography was performed via femoral catheter with magnification factor of 2.5 to 3.0, utilizing 0.1 X 0.1 ultra fine focal spot, manufactured by Shimadzu Seisakusho, Ltd. The standard angiograms were compared with magnification angiograms in a group of 67 patients with brain tumors and vascular disorders. The magnification angiography was more valuable than conventional angiography in 12 of 17 vascular tumors, while it was rarely valuable for diagnosis of vascular tumors. Aneurysms, occlusive diseases, collateral vessels, and capillary blush were also visualized to better advantage on magnification angiograms. Magnification cerebral angiography is a useful tool for elucidating small vascular branches, but further refinement in the design of focal spots and angiographic techinques is required for further improvement of magnification cerebral angiography."} {"id": "PMID:174022", "title": "[The rapid microscopical diagnosis of brain and spinal cord tumors by cryostat-cut frozen section (author's transl)].", "content": "The rapid histological diagnosis of neurosurgical biopsy material is of prime importance for the neurosurgeon. Cryostat-cut sections of fresh frozen tissues have been used in our department. The surgical materials are rapidly frozen at - 150 degrees C, and serial sections, 10 microns thick, are cut in a cryostat at -18 degrees to -20 degrees C. The sections are adhered to cover glasses and stained with Metachrome solution (a mixture of 1% Azure A and 0.5% Erie Garnet B). The rapid and accurate diagnosis can be obtained within 5 minutes. The advantage of cryostat-cut frozen section is the preservation of cell density and tissue architecture, which is most important in the diagnosis of neurosurgical materials, especially in case of diffusely infiltrating glioma. The previously reported methods, such as smear technique and frozen sections by using freezing microtome are also reviewed and discussed.", "contents": "[The rapid microscopical diagnosis of brain and spinal cord tumors by cryostat-cut frozen section (author's transl)]. The rapid histological diagnosis of neurosurgical biopsy material is of prime importance for the neurosurgeon. Cryostat-cut sections of fresh frozen tissues have been used in our department. The surgical materials are rapidly frozen at - 150 degrees C, and serial sections, 10 microns thick, are cut in a cryostat at -18 degrees to -20 degrees C. The sections are adhered to cover glasses and stained with Metachrome solution (a mixture of 1% Azure A and 0.5% Erie Garnet B). The rapid and accurate diagnosis can be obtained within 5 minutes. The advantage of cryostat-cut frozen section is the preservation of cell density and tissue architecture, which is most important in the diagnosis of neurosurgical materials, especially in case of diffusely infiltrating glioma. The previously reported methods, such as smear technique and frozen sections by using freezing microtome are also reviewed and discussed."} {"id": "PMID:174023", "title": "[The effect of radiotherapy for glioblastoma: a review of 516 cases (author's transl)].", "content": "516 cases of supratentorial glioblastoma, treated in the Department of Surgical Neurology, University of Edinburgh from 1950 through 1970, were analysed with a particular attention to the effect of radiotherapy and the factors contributing to better prognosis. The length of postoperative survival was known in 349 cases and it was more than one month in 238 cases. A megavoltage linear accelerator was introduced in 1955 for radiotherapy of glioblastoma and steroids were started to be used almost routinely in 1966 for pre- and postoperative peritumoral cerebral edema. The policies of the treatment of glioblastoma in this series were; 1) to establish the histological diagnosis and 2) to prolong \"useful\" postoperative survival of the patient. Among the 516 cases, 271 cases (52.5%) were treated by biopsy alone. More radical procedures and/or radiotherapy were indicated only when survival of the patient was expected to be \"useful\" for himself and his family. \"Useful\" life was defined as the condition where the patient was conscious and orientated, and would, on the whole, be glad that he was still alive. Patients with disturbed consciousness, profound aphasia, bedridden or mentally disorganized, were regarded as having useless life. Radiotherapy, if indicated, was given by a 4-megavoltage linear accelerator to the whole brain with a total dose of 4500 rads in a period of 4 weeks. In order to evaluate the effect of radiotherapy, 238 cases who survived more than one month postoperatively were selected, because it took at least one month to complete the course of radiotherapy, because most cases with a biopsy alone survived less than one month, and because unexpected early death due to postoperative complications occurred in one month. The average survival for the irradiated 138 cases was 13.8 months, as compared to 5.2 months for the non-irradiated 100 cases. This difference of 8.6 months was highly significant as confirmed statistically by U-test. Although patients with profound aphasia or severe dimentia were not irradiated, aphasia and dimentia would not affect the length of biological survival of the patient. Therefore, the difference of 8.6 months could be considered as the biological effect of radiotherapy. Among the factors considered, young age, early epilepsy and relatively benign histology (astrocytoma, grade 3) appeared to be related to better prognosis. There was no evidence that a macroscopic circumscribed appearance would contribute to better prognosis. In conclusion, radiotherapy should be indicated for the cases whose survival is expected to be \"useful\", although its effect is limited.", "contents": "[The effect of radiotherapy for glioblastoma: a review of 516 cases (author's transl)]. 516 cases of supratentorial glioblastoma, treated in the Department of Surgical Neurology, University of Edinburgh from 1950 through 1970, were analysed with a particular attention to the effect of radiotherapy and the factors contributing to better prognosis. The length of postoperative survival was known in 349 cases and it was more than one month in 238 cases. A megavoltage linear accelerator was introduced in 1955 for radiotherapy of glioblastoma and steroids were started to be used almost routinely in 1966 for pre- and postoperative peritumoral cerebral edema. The policies of the treatment of glioblastoma in this series were; 1) to establish the histological diagnosis and 2) to prolong \"useful\" postoperative survival of the patient. Among the 516 cases, 271 cases (52.5%) were treated by biopsy alone. More radical procedures and/or radiotherapy were indicated only when survival of the patient was expected to be \"useful\" for himself and his family. \"Useful\" life was defined as the condition where the patient was conscious and orientated, and would, on the whole, be glad that he was still alive. Patients with disturbed consciousness, profound aphasia, bedridden or mentally disorganized, were regarded as having useless life. Radiotherapy, if indicated, was given by a 4-megavoltage linear accelerator to the whole brain with a total dose of 4500 rads in a period of 4 weeks. In order to evaluate the effect of radiotherapy, 238 cases who survived more than one month postoperatively were selected, because it took at least one month to complete the course of radiotherapy, because most cases with a biopsy alone survived less than one month, and because unexpected early death due to postoperative complications occurred in one month. The average survival for the irradiated 138 cases was 13.8 months, as compared to 5.2 months for the non-irradiated 100 cases. This difference of 8.6 months was highly significant as confirmed statistically by U-test. Although patients with profound aphasia or severe dimentia were not irradiated, aphasia and dimentia would not affect the length of biological survival of the patient. Therefore, the difference of 8.6 months could be considered as the biological effect of radiotherapy. Among the factors considered, young age, early epilepsy and relatively benign histology (astrocytoma, grade 3) appeared to be related to better prognosis. There was no evidence that a macroscopic circumscribed appearance would contribute to better prognosis. In conclusion, radiotherapy should be indicated for the cases whose survival is expected to be \"useful\", although its effect is limited."} {"id": "PMID:174024", "title": "[Morphological differentiation in vitro of human continuous and functional neuroblastoma cell line, NB-I under treatment of (But)2cAMP (author's transl)].", "content": "Human neuroblastoma cell line (NB-I), obtained from metastatic neck lymph node of 2.3 y-o, boy, is established and maintained in vitro for more than 3 years in our department. The cells have been proliferated in 10% calf serum in EAGLE's medium, in closed stational culture system. The cell line has characteristic activities of rather rapid growth (Tg = 40 or 50h, 1974) catecholamine metabolism and chromosomal abnormality, bearing two marker chromosomes. NB-I cells are uncloned because of co-adhesiveness but biochemically identified as adrenergic line. Morphologically, they are round or tear-drop like in shape with delicate short protoplasmic processes. NB-I cells exhibit remarkable morphological differentiation and maturation under treatment of (But)2cAMP (final concentration, 1mM/ml). A longer time (1-2 weeks) for differentiation, however, is needed in comparison with that of mouse neuroblastoma cell lines. The NB-I cells exhibit hypertrophy of cytoplasma and nuclei in size, elongation of cytoplasmic processes, as well as the tendency of flattness and multipolarity of cells. Electronmicroscopically, the cells that showed scant organella but plentiful polysomes in the specimen, obtained during autopsy, reveal an increase of cell organellae after implantation in vitro: Golgi apparatus, neurotubules and neural dense bodies appeared in cytoplasma. These organellae characteristic of sympathetic neuron are much more increased under treatment of (But)2cAMP in 3 weeks. Core-vesicle like dense bodies are extremely rich in periphery of perikaryon and elongated processes (100 - 150 mu in diameter). Microtubules are also increased, running in bundles in processes. The NB-I cells are considered to differentiate and approach to matured neurons in vitro.", "contents": "[Morphological differentiation in vitro of human continuous and functional neuroblastoma cell line, NB-I under treatment of (But)2cAMP (author's transl)]. Human neuroblastoma cell line (NB-I), obtained from metastatic neck lymph node of 2.3 y-o, boy, is established and maintained in vitro for more than 3 years in our department. The cells have been proliferated in 10% calf serum in EAGLE's medium, in closed stational culture system. The cell line has characteristic activities of rather rapid growth (Tg = 40 or 50h, 1974) catecholamine metabolism and chromosomal abnormality, bearing two marker chromosomes. NB-I cells are uncloned because of co-adhesiveness but biochemically identified as adrenergic line. Morphologically, they are round or tear-drop like in shape with delicate short protoplasmic processes. NB-I cells exhibit remarkable morphological differentiation and maturation under treatment of (But)2cAMP (final concentration, 1mM/ml). A longer time (1-2 weeks) for differentiation, however, is needed in comparison with that of mouse neuroblastoma cell lines. The NB-I cells exhibit hypertrophy of cytoplasma and nuclei in size, elongation of cytoplasmic processes, as well as the tendency of flattness and multipolarity of cells. Electronmicroscopically, the cells that showed scant organella but plentiful polysomes in the specimen, obtained during autopsy, reveal an increase of cell organellae after implantation in vitro: Golgi apparatus, neurotubules and neural dense bodies appeared in cytoplasma. These organellae characteristic of sympathetic neuron are much more increased under treatment of (But)2cAMP in 3 weeks. Core-vesicle like dense bodies are extremely rich in periphery of perikaryon and elongated processes (100 - 150 mu in diameter). Microtubules are also increased, running in bundles in processes. The NB-I cells are considered to differentiate and approach to matured neurons in vitro."} {"id": "PMID:174026", "title": "'Glioblastoma'. Induction of a reproducible autochonous tumor in rats with murine sarcoma virus.", "content": "Inoculation of 0.02 ml of high-titer Kirsten strain Murine Sarcoma Virus into the brains of 10-day-old Wistar/Furth rats yields, with 100 percent incidence, a uniform glioblastoma-like tumor within 16 days. Light and electronmicroscopy confirmed the neuroectodermal origin of the parenchymal cells. The remarkable vascular component was studied with extracellular tracers. The permeability of the abnormal endothelium to constituents of the blood vascular compartment was confirmed. Accessory vascular channels, and blood channels devoid of endothelium entirely, were observed. This reporducible system should provide a useful model for further studies of the biology of brain tumors.", "contents": "'Glioblastoma'. Induction of a reproducible autochonous tumor in rats with murine sarcoma virus. Inoculation of 0.02 ml of high-titer Kirsten strain Murine Sarcoma Virus into the brains of 10-day-old Wistar/Furth rats yields, with 100 percent incidence, a uniform glioblastoma-like tumor within 16 days. Light and electronmicroscopy confirmed the neuroectodermal origin of the parenchymal cells. The remarkable vascular component was studied with extracellular tracers. The permeability of the abnormal endothelium to constituents of the blood vascular compartment was confirmed. Accessory vascular channels, and blood channels devoid of endothelium entirely, were observed. This reporducible system should provide a useful model for further studies of the biology of brain tumors."} {"id": "PMID:174027", "title": "Jaw and blind reflexes in trigeminal nerve lesions. An electrodiagnostic study.", "content": "Eighteen patients with intracranial trigeminal nerve lesions were investigated electrodiagnostically. The trigeminal motor root function was studied on the basis of the jaw reflex and masseter myograms and was disturbed in all cases. The jaw reflexes were abnormal in 16 and the masseter myograms in eight cases. An impressive trigeminal sensory root function was obtained from blink reflex, which was abnormal in 12 cases. The results show the diagnostic value of bilateral recording of the jaw reflex in such patients.", "contents": "Jaw and blind reflexes in trigeminal nerve lesions. An electrodiagnostic study. Eighteen patients with intracranial trigeminal nerve lesions were investigated electrodiagnostically. The trigeminal motor root function was studied on the basis of the jaw reflex and masseter myograms and was disturbed in all cases. The jaw reflexes were abnormal in 16 and the masseter myograms in eight cases. An impressive trigeminal sensory root function was obtained from blink reflex, which was abnormal in 12 cases. The results show the diagnostic value of bilateral recording of the jaw reflex in such patients."} {"id": "PMID:174035", "title": "Type V hyperlipoproteinaemia: a family study.", "content": "Family screening for hyperlipoproteinaemia was undertaken when a patient presented with myocardial infarction in association with Type V hyperlipoproteinaemia. The clinical features of this unusual form of hyperlipoproteinaemia are discussed together with its frequency in the general population and in relatives of affected patients.", "contents": "Type V hyperlipoproteinaemia: a family study. Family screening for hyperlipoproteinaemia was undertaken when a patient presented with myocardial infarction in association with Type V hyperlipoproteinaemia. The clinical features of this unusual form of hyperlipoproteinaemia are discussed together with its frequency in the general population and in relatives of affected patients."} {"id": "PMID:174039", "title": "Paget's disease of the vulva. Recurrence in skin grafts.", "content": "This report is directed toward problems with recurrent Paget's disease of the vulva. In addition, the behavior of a skin graft within the anal canal and recurrent disease within two separate grafts warrants recognition.", "contents": "Paget's disease of the vulva. Recurrence in skin grafts. This report is directed toward problems with recurrent Paget's disease of the vulva. In addition, the behavior of a skin graft within the anal canal and recurrent disease within two separate grafts warrants recognition."} {"id": "PMID:174038", "title": "Herpesvirus infection in the newborn. Its treatment by exchange transfusion and adenosine arabinoside.", "content": "A case is reported of herpesvirus infection in the newborn following maternal genital herpesvirus infection. The rationale for treating a newborn infant with signs of disseminated herpesvirus infection by exchange transfusion in addition to adenosine arabinoside is discussed. Because of the lack of data concerning therapy for a disease with a 50 to 100% mortality rate, it is important to present material such as this in order to provide information about possible new therapeutic modalities.", "contents": "Herpesvirus infection in the newborn. Its treatment by exchange transfusion and adenosine arabinoside. A case is reported of herpesvirus infection in the newborn following maternal genital herpesvirus infection. The rationale for treating a newborn infant with signs of disseminated herpesvirus infection by exchange transfusion in addition to adenosine arabinoside is discussed. Because of the lack of data concerning therapy for a disease with a 50 to 100% mortality rate, it is important to present material such as this in order to provide information about possible new therapeutic modalities."} {"id": "PMID:174040", "title": "Trial of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; NSC-79037) in advanced bronchogenic carcinoma 1,2,3.", "content": "A total of 103 patients with lung cancer was treated with CCNU 130 mg/m2 orally every 6 weeks; 65 patients survived at least 6 weeks. Partial responses occurred in 7 patients. Leukopenia, thrombocytopenia, and nausea were frequent toxic effects. CCNU has slight efficacy in advanced lung cancer. No increase in survival was attributed to therapy.", "contents": "Trial of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; NSC-79037) in advanced bronchogenic carcinoma 1,2,3. A total of 103 patients with lung cancer was treated with CCNU 130 mg/m2 orally every 6 weeks; 65 patients survived at least 6 weeks. Partial responses occurred in 7 patients. Leukopenia, thrombocytopenia, and nausea were frequent toxic effects. CCNU has slight efficacy in advanced lung cancer. No increase in survival was attributed to therapy."} {"id": "PMID:174041", "title": "A phase III study in lung carcinoma comparing hexamethyl-melamine (NSC 13875) to dibromodulcitol (NSC 104800) 1,2.", "content": "A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma.", "contents": "A phase III study in lung carcinoma comparing hexamethyl-melamine (NSC 13875) to dibromodulcitol (NSC 104800) 1,2. A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma."} {"id": "PMID:174042", "title": "Solubilized nuclear DNA-dependent RNA polymerases from normal rat mammary glands and from transplantable R-35 rat mammary tumors.", "content": "The three major nuclear DNA-dependent RNA polymerases (enzymes I, II and III) were present in nuclear extracts from transplantable R-35 rat mammary tumors. Except for somewhat less enzyme III, their relative distribution resembled that of nuclear extracts from late-pregnant rats. When enzyme II from normal tissue extracts was incubated for RNA synthesis with cyclic AMP, inhibition was frequently observed, but this occurred less often with nuclear extracts from the R-35 tumor. In some experiments with both normal and tumor tissue, cyclic AMP and cyclic GMP increased the apparent activity of nucleolar enzyme Ib and nucleoplasmic enzyme II, respectively. Nuclear extracts from both normal and tumor tissue contain proteins which bind radioactive cyclic AMP and cyclic GMP. Their patterns of binding were not identical. These results are consistent with the following hypothesis: altered binding by the tumor of cyclic nucleotides to putative nuclear 'r-gulatory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to atative nuclear 'regularory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to and may be responsible for some of the differences in response to cyclic nucleotides that were observed. It is possible that such defects occur in other tumors, or even represent a fundamental defect in all cancer cells. Several explanations for these results are discussed.", "contents": "Solubilized nuclear DNA-dependent RNA polymerases from normal rat mammary glands and from transplantable R-35 rat mammary tumors. The three major nuclear DNA-dependent RNA polymerases (enzymes I, II and III) were present in nuclear extracts from transplantable R-35 rat mammary tumors. Except for somewhat less enzyme III, their relative distribution resembled that of nuclear extracts from late-pregnant rats. When enzyme II from normal tissue extracts was incubated for RNA synthesis with cyclic AMP, inhibition was frequently observed, but this occurred less often with nuclear extracts from the R-35 tumor. In some experiments with both normal and tumor tissue, cyclic AMP and cyclic GMP increased the apparent activity of nucleolar enzyme Ib and nucleoplasmic enzyme II, respectively. Nuclear extracts from both normal and tumor tissue contain proteins which bind radioactive cyclic AMP and cyclic GMP. Their patterns of binding were not identical. These results are consistent with the following hypothesis: altered binding by the tumor of cyclic nucleotides to putative nuclear 'r-gulatory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to atative nuclear 'regularory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to and may be responsible for some of the differences in response to cyclic nucleotides that were observed. It is possible that such defects occur in other tumors, or even represent a fundamental defect in all cancer cells. Several explanations for these results are discussed."} {"id": "PMID:174043", "title": "Stimulatory effect of a serum factor on DNA synthesis in isolated hepatoma nuclei.", "content": "A serum protein present in normal rat serum and absent from the serum of hepatoma-bearing animals at advanced stages has a stimulatory effect on 3H-thymidine incorporation into hepatoma cells in suspension. Liver cells maintained in a similar suspension are not affected by the factor. The stimulation appears to be at the level of chromatin or DNA. Isolated membrane-denuded nuclei from Morris hepatoma 7777 incorporate more 3H-TTP when the factor is present in the incubation mixture. Nuclei from host liver are not stimulated. The factor also stimulates incorporation of 3H-TTP in a system using calf thymus DNA as primer and an extracted DNA polymerase. In this system incorporation is stimulated with DNA polymerase from both tissues, host liver and hepatoma 7777. It is concluded that the factor does not act on the DNA polymerase but on chromatin or DNA.", "contents": "Stimulatory effect of a serum factor on DNA synthesis in isolated hepatoma nuclei. A serum protein present in normal rat serum and absent from the serum of hepatoma-bearing animals at advanced stages has a stimulatory effect on 3H-thymidine incorporation into hepatoma cells in suspension. Liver cells maintained in a similar suspension are not affected by the factor. The stimulation appears to be at the level of chromatin or DNA. Isolated membrane-denuded nuclei from Morris hepatoma 7777 incorporate more 3H-TTP when the factor is present in the incubation mixture. Nuclei from host liver are not stimulated. The factor also stimulates incorporation of 3H-TTP in a system using calf thymus DNA as primer and an extracted DNA polymerase. In this system incorporation is stimulated with DNA polymerase from both tissues, host liver and hepatoma 7777. It is concluded that the factor does not act on the DNA polymerase but on chromatin or DNA."} {"id": "PMID:174044", "title": "Study on the photochemical reaction of HCN and its polymer products relating to primary chemical evolution.", "content": "The photochemical reaction of HCN at 184.9 nm is studied in the gas phase. (CN)2, H2, CH4, NH3, N2H4, C2H6, and CH3NH2 are identified as gas phase products, and a reaction mechanism is proposed. HCN polymers are also obtained as solid reaction products, and their structure is investigated by Infrared Spectorscopy, UV-Visible Spectroscopy, Mass Spectrometry, and Amino Acid Analysis. The process and nature of the formation of the polymers are discussed.", "contents": "Study on the photochemical reaction of HCN and its polymer products relating to primary chemical evolution. The photochemical reaction of HCN at 184.9 nm is studied in the gas phase. (CN)2, H2, CH4, NH3, N2H4, C2H6, and CH3NH2 are identified as gas phase products, and a reaction mechanism is proposed. HCN polymers are also obtained as solid reaction products, and their structure is investigated by Infrared Spectorscopy, UV-Visible Spectroscopy, Mass Spectrometry, and Amino Acid Analysis. The process and nature of the formation of the polymers are discussed."} {"id": "PMID:174046", "title": "The influence of pinealectomy and of pinealectomy combined with thymectomy oncogenesis caused by polyoma virus in rats.", "content": "The inoculation of Polyoma virus suspension to neonatal pinealectomized rats did not provoke a growth of neoplasia. However, if the pinealectomy was combined with neonatal thymectomy, renal tumors occured in a rate of 50 of animals. An incidence of renal tumors was observed also in 57.6% of thymectomized rats, but not in non operated control group. The stimulating effect of pinealectomy on the growth of transplantable tumors has already been described several times (2, 3, 6, 8). The question of a possible change in the viral oncogenesis after pinealectomy was raised. For this reason Polyoma virus was used and its oncogenic effect was studied on the neonatally pinealectomized rats, on rats neonatally thymectomized and on neonatally pinealectomized rats which were simultaneously thymectomized.", "contents": "The influence of pinealectomy and of pinealectomy combined with thymectomy oncogenesis caused by polyoma virus in rats. The inoculation of Polyoma virus suspension to neonatal pinealectomized rats did not provoke a growth of neoplasia. However, if the pinealectomy was combined with neonatal thymectomy, renal tumors occured in a rate of 50 of animals. An incidence of renal tumors was observed also in 57.6% of thymectomized rats, but not in non operated control group. The stimulating effect of pinealectomy on the growth of transplantable tumors has already been described several times (2, 3, 6, 8). The question of a possible change in the viral oncogenesis after pinealectomy was raised. For this reason Polyoma virus was used and its oncogenic effect was studied on the neonatally pinealectomized rats, on rats neonatally thymectomized and on neonatally pinealectomized rats which were simultaneously thymectomized."} {"id": "PMID:174047", "title": "[Corticosterone, a synchronizing factor for liver cells].", "content": "The clone Fu 5 a of the Reuber Hepatoma cell line was incubated with corticosterone for 48 hours. The incorporation of labelled thymidine into DNA was inhibited to 10%. After this time corticosterone was removed from the medium. The DNA-synthesis increased for ten hours, the maximum was sixteen times higher than in the controls. The conclusion drawn was that corticosterone is able to block liver cells in a part of G1 phase of the cell cycle, so that the cells become synchronous.", "contents": "[Corticosterone, a synchronizing factor for liver cells]. The clone Fu 5 a of the Reuber Hepatoma cell line was incubated with corticosterone for 48 hours. The incorporation of labelled thymidine into DNA was inhibited to 10%. After this time corticosterone was removed from the medium. The DNA-synthesis increased for ten hours, the maximum was sixteen times higher than in the controls. The conclusion drawn was that corticosterone is able to block liver cells in a part of G1 phase of the cell cycle, so that the cells become synchronous."} {"id": "PMID:174048", "title": "A study of the immuno-suppressive activity of Herpes simplex virus type 2 and the tumor enhancing potential of the virus on Yoshida sarcoma.", "content": "The relative delays of Yoshida sarcoma (YS) tumor induction were used as indicator for the immunosuppressive potential caused by the subcutaneous infection of Sprague-Dawley rats with approximately 10(7) TCD50 HSV-2. The tumor formation is clearly accelerated and the number of tumors is increased as compared to sham injected rats. The impairment of immunity is at its maximum when the virus and the YS cells are applied simultaneously, whereas virus given after the tumor is of no consequence. The adoptive neutralization test of Winn showed that the neutralization potential of spleen cells originating from HSV-2 infected donors is decreased from day 8 to day 11 post infection but rturns back to normal a week later. The stimulation of spleen cells with PHA is reduced up to 50% of control values on day 6 to 8 post virus infection but PFC and RFC values are not noticeably affected and neither are the hemagglutination titres. The implications of the immuno-suppressive faculty of HSV-2 for human genital malignancies are discuss.ed.", "contents": "A study of the immuno-suppressive activity of Herpes simplex virus type 2 and the tumor enhancing potential of the virus on Yoshida sarcoma. The relative delays of Yoshida sarcoma (YS) tumor induction were used as indicator for the immunosuppressive potential caused by the subcutaneous infection of Sprague-Dawley rats with approximately 10(7) TCD50 HSV-2. The tumor formation is clearly accelerated and the number of tumors is increased as compared to sham injected rats. The impairment of immunity is at its maximum when the virus and the YS cells are applied simultaneously, whereas virus given after the tumor is of no consequence. The adoptive neutralization test of Winn showed that the neutralization potential of spleen cells originating from HSV-2 infected donors is decreased from day 8 to day 11 post infection but rturns back to normal a week later. The stimulation of spleen cells with PHA is reduced up to 50% of control values on day 6 to 8 post virus infection but PFC and RFC values are not noticeably affected and neither are the hemagglutination titres. The implications of the immuno-suppressive faculty of HSV-2 for human genital malignancies are discuss.ed."} {"id": "PMID:174050", "title": "Effects of the diazafluoranthen derivative AC-3579 (NSC-170561), a new experimental antitumour drug, on rat hepatoma.", "content": "The effects of AC-3579 (NSC-170561), a new experimental antitumour drug which depresses phospholipid catabolism in liver, were compared in rat aflatoxin-induced hepatoma and in non-neoplastic hepatocytes surrounding the tumour. Ultrastructural lesions, characterized by the hypertrophy of the smooth endoplasmic reticulum and the presence of lamellate cytosomes appeared in both tissues. They were less marked in hepatoma than in non-neoplastic cells. As in control livers, they were related to an invrease in pohspholipid concentration due to the decrease of phospholipid breakdown. In addition, chemical analysis demonstrated differences between hepatoma, non-neoplastic aflatoxin-treated liver and control liver: total and free cholesterol were decreased, relative concentration of sphingomyelin increased and that of phosphatidylethanolamine decreased by about 50%, in both hepatoma and non-neoplastic liver. Phospholipid concentration was decreased by 50% in tumour cells. After AC-3579 treatment total cholesterol was increased 3.2 fold in non-neoplastic liver and 2.5 fold in hepatoma but not in control liver.", "contents": "Effects of the diazafluoranthen derivative AC-3579 (NSC-170561), a new experimental antitumour drug, on rat hepatoma. The effects of AC-3579 (NSC-170561), a new experimental antitumour drug which depresses phospholipid catabolism in liver, were compared in rat aflatoxin-induced hepatoma and in non-neoplastic hepatocytes surrounding the tumour. Ultrastructural lesions, characterized by the hypertrophy of the smooth endoplasmic reticulum and the presence of lamellate cytosomes appeared in both tissues. They were less marked in hepatoma than in non-neoplastic cells. As in control livers, they were related to an invrease in pohspholipid concentration due to the decrease of phospholipid breakdown. In addition, chemical analysis demonstrated differences between hepatoma, non-neoplastic aflatoxin-treated liver and control liver: total and free cholesterol were decreased, relative concentration of sphingomyelin increased and that of phosphatidylethanolamine decreased by about 50%, in both hepatoma and non-neoplastic liver. Phospholipid concentration was decreased by 50% in tumour cells. After AC-3579 treatment total cholesterol was increased 3.2 fold in non-neoplastic liver and 2.5 fold in hepatoma but not in control liver."} {"id": "PMID:174051", "title": "Fat accumulation in tha adrenal gland: effect of oestradiol benzoate on the zona reticularis of the Mongolian gerbil adrenal gland.", "content": "Oestrogen promotes accumulation of abundant lipid droplets in the zona reticularis of the Mongolian gerbil. Lipid was observed in zona reticularis parenchymal cells but droplets were especially numerous in macrophages. Enlargement of lipid droplets was facilitated by an envelopment with lysosomal membranes. Focal areas or entire parenchymal cells may then undergo degeneration and necrosis and be incorporated into large macrophages recognizable by distinct areas of lipid-containing material as well as by small mitochondria with short cristae. Oestrogen may well act directly on zona reticularis cells inasmuch as nafoxidine, an antioestrogen, prevents these changes. Zona fasciculata cells were identical to those in controls and an intermediate region between the zona fasciculata and zona reticularis persists, although concentric whorls of rough endoplasmic reticulum seen in controls were replaced by disorganized, randomly dispersed cisternae of rough endoplasmic reticulum. Oestrogen does not elevate cortisol in the plasma.", "contents": "Fat accumulation in tha adrenal gland: effect of oestradiol benzoate on the zona reticularis of the Mongolian gerbil adrenal gland. Oestrogen promotes accumulation of abundant lipid droplets in the zona reticularis of the Mongolian gerbil. Lipid was observed in zona reticularis parenchymal cells but droplets were especially numerous in macrophages. Enlargement of lipid droplets was facilitated by an envelopment with lysosomal membranes. Focal areas or entire parenchymal cells may then undergo degeneration and necrosis and be incorporated into large macrophages recognizable by distinct areas of lipid-containing material as well as by small mitochondria with short cristae. Oestrogen may well act directly on zona reticularis cells inasmuch as nafoxidine, an antioestrogen, prevents these changes. Zona fasciculata cells were identical to those in controls and an intermediate region between the zona fasciculata and zona reticularis persists, although concentric whorls of rough endoplasmic reticulum seen in controls were replaced by disorganized, randomly dispersed cisternae of rough endoplasmic reticulum. Oestrogen does not elevate cortisol in the plasma."} {"id": "PMID:174053", "title": "Early effects of inorganic lead on immature rat brain mitochondrial respiration.", "content": "Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun on ad libitum feedins containing 4% lead carbonate when their pups were 2 weeks old. Mitochondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically, NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P less than 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P less than 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P less than 0.02; cerebrum, P less than 0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P less than 0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P less than 0.01; cerebrum, P less than 0.05). The decrease in control ratios in cerebellar mitochondria from animals receivint lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P less than 0.01; cerebral hemisphers, P less than 0.05). In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P less than 0.001) increase within 2 days of beginning feedings and a significant (P less than 0.01) decrease after 2 weeks of feedings.", "contents": "Early effects of inorganic lead on immature rat brain mitochondrial respiration. Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun on ad libitum feedins containing 4% lead carbonate when their pups were 2 weeks old. Mitochondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically, NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P less than 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P less than 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P less than 0.02; cerebrum, P less than 0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P less than 0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P less than 0.01; cerebrum, P less than 0.05). The decrease in control ratios in cerebellar mitochondria from animals receivint lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P less than 0.01; cerebral hemisphers, P less than 0.05). In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P less than 0.001) increase within 2 days of beginning feedings and a significant (P less than 0.01) decrease after 2 weeks of feedings."} {"id": "PMID:174054", "title": "Apneic spells and sleep states in preterm infants.", "content": "The incidence of apneic spells during different sleep states active sleep, quiet sleep, and undifferentiated sleep was determined in eight preterm infants of 30 to 35 weeks' conceptional age, by means of a polygraphic recording technique. They were free of perinatal and postnatal complications other than apnea. During their active or rapid eye movement (REM) sleep they showed significantly more apneic episodes which were also longer lasting and they were accompanied by bradycardia of a greater severity. The organization of the immature nervous system with a preponderance of inhibitory synaptic connections and the additional inhibition of spinal motoneurons during REM sleep are likely to be the cause of apneic spells in otherwise \"normal\" preterm infants.", "contents": "Apneic spells and sleep states in preterm infants. The incidence of apneic spells during different sleep states active sleep, quiet sleep, and undifferentiated sleep was determined in eight preterm infants of 30 to 35 weeks' conceptional age, by means of a polygraphic recording technique. They were free of perinatal and postnatal complications other than apnea. During their active or rapid eye movement (REM) sleep they showed significantly more apneic episodes which were also longer lasting and they were accompanied by bradycardia of a greater severity. The organization of the immature nervous system with a preponderance of inhibitory synaptic connections and the additional inhibition of spinal motoneurons during REM sleep are likely to be the cause of apneic spells in otherwise \"normal\" preterm infants."} {"id": "PMID:174056", "title": "Effect of breast-feeding on seroresponse of infants to oral poliovirus vaccination.", "content": "Three hundred Indian infants between 6 and 51 weeks of age were divided into six groups and given three doses of trivalent oral polio vaccine (OPV) of known adequate potency. One group was on unrestricted breast-feeding with mandatory breast-feed during the interval between 30 minutes before and 15 minutes after each dose of OPV. In four groups of infants breast-feeding was withheld for three, four, five, and six hours both before and after each dose of OPV. The sixth group was bottle-fed. Samples of blood were collected from all infants before vaccination and from 227 infants further samples were collected four weeks after the first and/or third doses of OPV. Antibody responses to poliovirus types 1, 2, and 3 were determined following one dose and three doses of OPV, and the rates of response were found to be approximately equal in all groups of breast-fed infants irrespective of their feeding schedules, as well as in bottle-fed infants. Thus breast-feeding is shown to have no inhibitory effect on antibody response of infants beyond the newborn period to OPV.", "contents": "Effect of breast-feeding on seroresponse of infants to oral poliovirus vaccination. Three hundred Indian infants between 6 and 51 weeks of age were divided into six groups and given three doses of trivalent oral polio vaccine (OPV) of known adequate potency. One group was on unrestricted breast-feeding with mandatory breast-feed during the interval between 30 minutes before and 15 minutes after each dose of OPV. In four groups of infants breast-feeding was withheld for three, four, five, and six hours both before and after each dose of OPV. The sixth group was bottle-fed. Samples of blood were collected from all infants before vaccination and from 227 infants further samples were collected four weeks after the first and/or third doses of OPV. Antibody responses to poliovirus types 1, 2, and 3 were determined following one dose and three doses of OPV, and the rates of response were found to be approximately equal in all groups of breast-fed infants irrespective of their feeding schedules, as well as in bottle-fed infants. Thus breast-feeding is shown to have no inhibitory effect on antibody response of infants beyond the newborn period to OPV."} {"id": "PMID:174057", "title": "Pediatric familial type II hyperlipoproteinemia: therapy with diet and colestipol resin.", "content": "Effects of a low-cholesterol, polyunsaturate-rich diet and a synthetic organic bile sequestrant polymer (U26,597A, colestipol) were studied in 21 children, heterozygous for familial hypercholesterolemia. Total cholesterol, beta-lipoprotein cholesterol, and triglyceride were measured twice on habitual diet, monthly for six months on a low-cholesterol diet, and monthly for six months on low-cholesterol diet plus 10 gm of colestipol per day. Total cholesterol (mean +/- 1 SD) was 295 +/- 37 on habitual diet, 278 +/- 29 on low-cholesterol diet, and fell significantly to 242 +/- 29 mg/100 ml on diet plus colestipol. Low-density lipoprotein (LDL) cholesterol was 234 +/- 37 on habitual diet, 220 +/- 28 on low-cholesterol diet, and fell significantly to 179 +/- 26 mg/100 ml on diet plus drug. Plasma triglyceride levels on habitual diet were 79 +/- 31, remained unchanged on low-cholesterol diet, 86 +/- 22, and were unaffected by low-cholesterol diet plus drug, 85 +/- 17 mg/100 ml. On diet alone, plasma LDL was not normalized (less than 170 mg/100 ml) in any of the 21 children, and cholesterol fell to within normal limits (less than 230 mg/100 ml) in only one child. The combination of diet plus colestipol resin normalized total and LDL cholesterol in 52% of the children. Cholesterol was lowered to a \"moderately elevated\" range of 230 to 250 mg/100 ml in an additional 14% of the children and LDL was lowered to a range of 170 to 190 mg/100 ml in an additional 29%. In 33% of the children, cholesterol remained greater than 250 mg/100 ml despite diet plus colestipol, while LDL was greater than 190 mg/100 ml in 19%. Colestipol is an effective and well-tolerated cholesterol lowering compound which, in conjunction with diet, may prove to be very useful in the treatment of children heterozygous for familial hypercholesterolemia.", "contents": "Pediatric familial type II hyperlipoproteinemia: therapy with diet and colestipol resin. Effects of a low-cholesterol, polyunsaturate-rich diet and a synthetic organic bile sequestrant polymer (U26,597A, colestipol) were studied in 21 children, heterozygous for familial hypercholesterolemia. Total cholesterol, beta-lipoprotein cholesterol, and triglyceride were measured twice on habitual diet, monthly for six months on a low-cholesterol diet, and monthly for six months on low-cholesterol diet plus 10 gm of colestipol per day. Total cholesterol (mean +/- 1 SD) was 295 +/- 37 on habitual diet, 278 +/- 29 on low-cholesterol diet, and fell significantly to 242 +/- 29 mg/100 ml on diet plus colestipol. Low-density lipoprotein (LDL) cholesterol was 234 +/- 37 on habitual diet, 220 +/- 28 on low-cholesterol diet, and fell significantly to 179 +/- 26 mg/100 ml on diet plus drug. Plasma triglyceride levels on habitual diet were 79 +/- 31, remained unchanged on low-cholesterol diet, 86 +/- 22, and were unaffected by low-cholesterol diet plus drug, 85 +/- 17 mg/100 ml. On diet alone, plasma LDL was not normalized (less than 170 mg/100 ml) in any of the 21 children, and cholesterol fell to within normal limits (less than 230 mg/100 ml) in only one child. The combination of diet plus colestipol resin normalized total and LDL cholesterol in 52% of the children. Cholesterol was lowered to a \"moderately elevated\" range of 230 to 250 mg/100 ml in an additional 14% of the children and LDL was lowered to a range of 170 to 190 mg/100 ml in an additional 29%. In 33% of the children, cholesterol remained greater than 250 mg/100 ml despite diet plus colestipol, while LDL was greater than 190 mg/100 ml in 19%. Colestipol is an effective and well-tolerated cholesterol lowering compound which, in conjunction with diet, may prove to be very useful in the treatment of children heterozygous for familial hypercholesterolemia."} {"id": "PMID:174058", "title": "Studies on chromoproteins of cardiac and skeletal muscle of caimans (Caiman sclerops).", "content": "In a number of caimans (Caiman sclerops) we were unable to find traces of myoglobin in any of the histologically clearly cross-striated cardiac and skeletal muscles using spectrometric methods. The red colour of the heart is due to a high concentration of cytochrome c. This substance was also found in the muscles of the neck, back, tail, and the anterior extremities.", "contents": "Studies on chromoproteins of cardiac and skeletal muscle of caimans (Caiman sclerops). In a number of caimans (Caiman sclerops) we were unable to find traces of myoglobin in any of the histologically clearly cross-striated cardiac and skeletal muscles using spectrometric methods. The red colour of the heart is due to a high concentration of cytochrome c. This substance was also found in the muscles of the neck, back, tail, and the anterior extremities."} {"id": "PMID:174060", "title": "Potential use of ascorbic acid as a pituitary and adrenal scintigraphic agent.", "content": "The distribution of intravenously administered 14C-ascorbic acid (AA) into various tissues of the dog, and the effect of dexamethasone and ACTH administration on the AA distribution was studied. As a function of time, the differences of 14C-AA distribution between adrenal and surrounding organs become greater, and 24 hours after the administration of the dose, the adrenal to liver ratio, as well as adrenal to kidney, is about 10:1. Also concentration of AA in the pituitary showed a gradual increase and reached its peak between 24 and 48 hours. Dexamethasone administration lowered significantly the uptake of 14C-AA by the adrenals, but did not affect the uptake by the pituitary. Three consecutive days administration of ACTH did not affect the uptake of the drug by either glands, but one single dose of ACTH administered one hour prior to the 14C-AA increased the uptake of AA by both glands. These results indicate that properly labeled AA may be an effective pituitary and adrenal scanning agent. Possible ways of labeling AA without changing its pharmacological properties are suggested.", "contents": "Potential use of ascorbic acid as a pituitary and adrenal scintigraphic agent. The distribution of intravenously administered 14C-ascorbic acid (AA) into various tissues of the dog, and the effect of dexamethasone and ACTH administration on the AA distribution was studied. As a function of time, the differences of 14C-AA distribution between adrenal and surrounding organs become greater, and 24 hours after the administration of the dose, the adrenal to liver ratio, as well as adrenal to kidney, is about 10:1. Also concentration of AA in the pituitary showed a gradual increase and reached its peak between 24 and 48 hours. Dexamethasone administration lowered significantly the uptake of 14C-AA by the adrenals, but did not affect the uptake by the pituitary. Three consecutive days administration of ACTH did not affect the uptake of the drug by either glands, but one single dose of ACTH administered one hour prior to the 14C-AA increased the uptake of AA by both glands. These results indicate that properly labeled AA may be an effective pituitary and adrenal scanning agent. Possible ways of labeling AA without changing its pharmacological properties are suggested."} {"id": "PMID:174061", "title": "Hydrolysis in 2'-chloro-2'-deoxy nucleosides, -nucleotides and -polynucleotides to arabinose-derivatives.", "content": "The rate of hydrolysis of 2'-chloro-2'-deoxycytidine and -uridine, and their 5'-phosphates, -diphosphates and polymers to the corresponding arabinocytidine and arabinouridine derivatives in the presence of Tris-HCL pH 8.9 is determined. This rate is highest for the nucleosides, less for the 5'-phosphates and 5'-diphosphates and even less for the polynucleotides. In the the 2'-chloro-2'-deoxyuridine series the O2, 2'-cyclonucleoside was formed in addition to the arabinonucleoside.", "contents": "Hydrolysis in 2'-chloro-2'-deoxy nucleosides, -nucleotides and -polynucleotides to arabinose-derivatives. The rate of hydrolysis of 2'-chloro-2'-deoxycytidine and -uridine, and their 5'-phosphates, -diphosphates and polymers to the corresponding arabinocytidine and arabinouridine derivatives in the presence of Tris-HCL pH 8.9 is determined. This rate is highest for the nucleosides, less for the 5'-phosphates and 5'-diphosphates and even less for the polynucleotides. In the the 2'-chloro-2'-deoxyuridine series the O2, 2'-cyclonucleoside was formed in addition to the arabinonucleoside."} {"id": "PMID:174066", "title": "The influence of fluphenazine on the interaction of noradrenaline and serotonin.", "content": "The neurotransmitter catecholamines control metabolism 5-HT in pineal gland by stimulating pineal serotonin-N-acetyltransferase (EC 2.3.1.5) activity [1, 2]. To prove the influence of FP on the metabolism 5-HT provoked by norepinephrine was tested. Rat pineal gland were incubated in media containing 5-HT- 14C or 5-HT- 14C and FP (1-10(-6)-1-10(-4) M). Norepinephrine (1-10(-6)-1-10(-4)M) was added at the start of the experiment. The level of cyclic 3',5'-AMP, activity of HIOMT and metabolites of 5-HT-14C was examined. The results have suggested that the FP inhibit the provoked by norepinephrine metabolism of 5-HT in the rat pineal gland by decrease the formation of c-3',5'-AMP.", "contents": "The influence of fluphenazine on the interaction of noradrenaline and serotonin. The neurotransmitter catecholamines control metabolism 5-HT in pineal gland by stimulating pineal serotonin-N-acetyltransferase (EC 2.3.1.5) activity [1, 2]. To prove the influence of FP on the metabolism 5-HT provoked by norepinephrine was tested. Rat pineal gland were incubated in media containing 5-HT- 14C or 5-HT- 14C and FP (1-10(-6)-1-10(-4) M). Norepinephrine (1-10(-6)-1-10(-4)M) was added at the start of the experiment. The level of cyclic 3',5'-AMP, activity of HIOMT and metabolites of 5-HT-14C was examined. The results have suggested that the FP inhibit the provoked by norepinephrine metabolism of 5-HT in the rat pineal gland by decrease the formation of c-3',5'-AMP."} {"id": "PMID:174067", "title": "Viral hepatitis--a primer: 1. Epidem.iology.", "content": "Hepatitis A is most often transmitted by the fecal-oral route under conditions of crowding, poor hygiene, and prolonged exposure to infected persons. Direct spread of hepatitis B via person-to person contact has only recently been proved. Hepatitis B is usually transmitted indirectly proved. Hepatitis B is usually transmitted indirectly by percutaneous routes, and the increase in drug abuse has brought about a change in its epidemiologic pattern.", "contents": "Viral hepatitis--a primer: 1. Epidem.iology. Hepatitis A is most often transmitted by the fecal-oral route under conditions of crowding, poor hygiene, and prolonged exposure to infected persons. Direct spread of hepatitis B via person-to person contact has only recently been proved. Hepatitis B is usually transmitted indirectly proved. Hepatitis B is usually transmitted indirectly by percutaneous routes, and the increase in drug abuse has brought about a change in its epidemiologic pattern."} {"id": "PMID:174069", "title": "[Preparation of highly puried pepsin by aminosilichrome chromatography].", "content": "The procedure for preparing highly purfied pepsin by chromatography on silicon dioxide with attached aminogroups (aminosilochrome) has been devised. Pepsin is eluated step=by-step: 0.0025 M and 0.05 M HCl. Results of disc-electrophoresis of purified pepsin bive evidence that the resultant preparation contains no admixtures. The activity of purified pepsin is 69 units per mg.", "contents": "[Preparation of highly puried pepsin by aminosilichrome chromatography]. The procedure for preparing highly purfied pepsin by chromatography on silicon dioxide with attached aminogroups (aminosilochrome) has been devised. Pepsin is eluated step=by-step: 0.0025 M and 0.05 M HCl. Results of disc-electrophoresis of purified pepsin bive evidence that the resultant preparation contains no admixtures. The activity of purified pepsin is 69 units per mg."} {"id": "PMID:174073", "title": "Cellular levels of feedback regulator of adenylate cyclase and the effect of epinephrine and insulin.", "content": "We have obtained direct evidence that shows the cellular formation and subsequent release of a potent inhibitor (feedback regulator) of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by adipocytes, upon stimulation with epinephrine. The appearance of such a feedback regulator in adipocytes preceded its release into the medium. During a 30 min incubation, intracellular regulator levels rose rapidly and reached 39-61 units/g of adipocyte at 10 min. Release of inhibitor into the medium increased slowly and was 11-16 units/g of adipocyte at 10 min. Upon continued incubation, the cells at 30 min contained 30-41 units/g of ingibitor, slightly less than the content at 30 min; meanwhile, the medium content rose more than 3-fold. The inhibitor from both locations appeared to have the same characteristics, judging from the purification procedures and the biological activities on hormone-stimulated adenylate cyclase. Adenylate cyclase was inhibited by the feedback regulator in vitro when either epinephrine, corticotropin (ACTH), or glucagon was used as activator. The site of action of this inhibitor is therefore most likely beyond the specific hormone receptors. A new in vitro action of insulin has been found. Insulin, 50-500 microunits/ml, inhibited the formation and release of this factor from isolated rat or hamster adipocytes by 29-81% after these cells were stimulated by hormones that raise intracellular adenosine 3':5'-cyclic monophosphate. This factor enhaced the effect of insulin in lowering the adenosine 3':5'-cyclic monophosphate levels in fresh rat adipocytes. A reduced formation of such a factor may modify the metabolic events in adipocytes, and some as yet unexplained effects of insulin could therefore be linked to the metabolic effects of this factor.", "contents": "Cellular levels of feedback regulator of adenylate cyclase and the effect of epinephrine and insulin. We have obtained direct evidence that shows the cellular formation and subsequent release of a potent inhibitor (feedback regulator) of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by adipocytes, upon stimulation with epinephrine. The appearance of such a feedback regulator in adipocytes preceded its release into the medium. During a 30 min incubation, intracellular regulator levels rose rapidly and reached 39-61 units/g of adipocyte at 10 min. Release of inhibitor into the medium increased slowly and was 11-16 units/g of adipocyte at 10 min. Upon continued incubation, the cells at 30 min contained 30-41 units/g of ingibitor, slightly less than the content at 30 min; meanwhile, the medium content rose more than 3-fold. The inhibitor from both locations appeared to have the same characteristics, judging from the purification procedures and the biological activities on hormone-stimulated adenylate cyclase. Adenylate cyclase was inhibited by the feedback regulator in vitro when either epinephrine, corticotropin (ACTH), or glucagon was used as activator. The site of action of this inhibitor is therefore most likely beyond the specific hormone receptors. A new in vitro action of insulin has been found. Insulin, 50-500 microunits/ml, inhibited the formation and release of this factor from isolated rat or hamster adipocytes by 29-81% after these cells were stimulated by hormones that raise intracellular adenosine 3':5'-cyclic monophosphate. This factor enhaced the effect of insulin in lowering the adenosine 3':5'-cyclic monophosphate levels in fresh rat adipocytes. A reduced formation of such a factor may modify the metabolic events in adipocytes, and some as yet unexplained effects of insulin could therefore be linked to the metabolic effects of this factor."} {"id": "PMID:174074", "title": "The effect of nerve growth factor on cycle AMP levels in superior cerival ganglia of the rat.", "content": "Nerve growth factor (NGF) produces a several-fold increase in the cyclic AMP concentration in rat superior cervical ganglia in organ culture within 5 min. An increase can be seen with as little as 40 ng/ml of NGF. Oxidized NGF is without effect. The increase in the cAMP concentration produced by NGF is prevented by the addition of antiserum to NGF.", "contents": "The effect of nerve growth factor on cycle AMP levels in superior cerival ganglia of the rat. Nerve growth factor (NGF) produces a several-fold increase in the cyclic AMP concentration in rat superior cervical ganglia in organ culture within 5 min. An increase can be seen with as little as 40 ng/ml of NGF. Oxidized NGF is without effect. The increase in the cAMP concentration produced by NGF is prevented by the addition of antiserum to NGF."} {"id": "PMID:174075", "title": "Mapping of biological functions on RNA of avian tumor viruses: location of regions required for transformation and determination of host range.", "content": "A map of the large T1 oligonucleotides of the RNA of Prague Rous sarcoma virus, strain B (Pr RSVb) has recently been established (Coffin and Billeter, submitted for publication). Since the RNA of Rous associated virus, type 1 (RAV-1) lacks many of the large 1 oligonucleotides of Pr RSV-B and contains others not present in the latter, the RNA of recombinants between RAV-1 and Pr RSV-B could be analyzed with regard to the origin of its sequences. Recombinants were selected for transforming capacity (characteristic for Pr RSV-B) and ability to grow on C/B chicken fibroblasts (characteristic for RAV-1). Four out of five recombinants examined had undergone at least two crossovers. The set of Pr RSV-B-specific oligonucleotides present in all recombinants defined an RNA region near the poly(A) segment; this must contain genetic information required for transformation required for transformation (the onc function). All recombinants lost a set of contiguous Pr RSV-B-specific oligonucleotides and concomitantly acquired a set of RAV-1-specific oligonucleotides. These define a region in the middle section of the oligonucleotide map, all or some of which must be required for determining growth capacity on C/B cells (the env function).", "contents": "Mapping of biological functions on RNA of avian tumor viruses: location of regions required for transformation and determination of host range. A map of the large T1 oligonucleotides of the RNA of Prague Rous sarcoma virus, strain B (Pr RSVb) has recently been established (Coffin and Billeter, submitted for publication). Since the RNA of Rous associated virus, type 1 (RAV-1) lacks many of the large 1 oligonucleotides of Pr RSV-B and contains others not present in the latter, the RNA of recombinants between RAV-1 and Pr RSV-B could be analyzed with regard to the origin of its sequences. Recombinants were selected for transforming capacity (characteristic for Pr RSV-B) and ability to grow on C/B chicken fibroblasts (characteristic for RAV-1). Four out of five recombinants examined had undergone at least two crossovers. The set of Pr RSV-B-specific oligonucleotides present in all recombinants defined an RNA region near the poly(A) segment; this must contain genetic information required for transformation required for transformation (the onc function). All recombinants lost a set of contiguous Pr RSV-B-specific oligonucleotides and concomitantly acquired a set of RAV-1-specific oligonucleotides. These define a region in the middle section of the oligonucleotide map, all or some of which must be required for determining growth capacity on C/B cells (the env function)."} {"id": "PMID:174076", "title": "On the iron-sulfur cluster in hydrogenase from Clostridium pasteurianum W5.", "content": "Hydrogenase, purified to an average specific activity of 328 mumol of H2 evolved/(min X mg of protein) from Clostridium pasteurianum W5, was found to have 4-5 Fe and 4-5 labile sulfur atoms per molecule of 60,000 molecular weight, in contrast with earlier reports of 12 Fe per molecule. Displacement of the iron-sulfur cluster from hydrogenase by thiophenol in 80% hexamethyl phosphoramide:20% H2O yielded the Fe4S4 (thiophenyl)4 dianion according to absorption spectroscopy. Electron paramagnetic resonance spectroscopy at 12 K showed that the iron-sulfur cluster in the enzyme could be reduced by the H2 to a state (g-values of 2.098, 1.970, and 1.898) similar to that in reduced ferredoxin and could be oxidized by dichlorophenolindophenol or H+ to a state (g-values at 2.099, 2.041, and 2.001) similar to that in high potential iron-sulfur proteins. These oxidations and reductions appeared to occur within the turnover time of the enzyme. Deuterium failed to narrow the electron paramagnetic resonance signal in either state, but the competitive inhibitor carbon monoxide reversibly formed a compound with either state and substantially altered the electron paramagnetic resonance. 13CO produced a broadening of these signals, suggesting the formation of a direct CO complex with the iron-sulfur cluster. These data are consistent with a model of the active site of the enzyme in which a four-iron four-sulfur cluster is a component that can accept one or two electrons from and donate either one or two electrons to substrates, and in which the iron-sulfur cluster serves as the site of binding of gaseous ligands.", "contents": "On the iron-sulfur cluster in hydrogenase from Clostridium pasteurianum W5. Hydrogenase, purified to an average specific activity of 328 mumol of H2 evolved/(min X mg of protein) from Clostridium pasteurianum W5, was found to have 4-5 Fe and 4-5 labile sulfur atoms per molecule of 60,000 molecular weight, in contrast with earlier reports of 12 Fe per molecule. Displacement of the iron-sulfur cluster from hydrogenase by thiophenol in 80% hexamethyl phosphoramide:20% H2O yielded the Fe4S4 (thiophenyl)4 dianion according to absorption spectroscopy. Electron paramagnetic resonance spectroscopy at 12 K showed that the iron-sulfur cluster in the enzyme could be reduced by the H2 to a state (g-values of 2.098, 1.970, and 1.898) similar to that in reduced ferredoxin and could be oxidized by dichlorophenolindophenol or H+ to a state (g-values at 2.099, 2.041, and 2.001) similar to that in high potential iron-sulfur proteins. These oxidations and reductions appeared to occur within the turnover time of the enzyme. Deuterium failed to narrow the electron paramagnetic resonance signal in either state, but the competitive inhibitor carbon monoxide reversibly formed a compound with either state and substantially altered the electron paramagnetic resonance. 13CO produced a broadening of these signals, suggesting the formation of a direct CO complex with the iron-sulfur cluster. These data are consistent with a model of the active site of the enzyme in which a four-iron four-sulfur cluster is a component that can accept one or two electrons from and donate either one or two electrons to substrates, and in which the iron-sulfur cluster serves as the site of binding of gaseous ligands."} {"id": "PMID:174077", "title": "Human papillomavirus DNA: physical map.", "content": "Human papillomavirus (HPV) DNA form I (supercoiled) was prepared from plantar warts. HPV DNA was cleaved with restriction enzymes obtained from the following sources: escherichia coli (EcoRI), Hemophilus influenzae strain Rd (both unfractionated Hind and aeparated HindII and HindIII enzymes) and Hemophilus parainfluenzae (HpaI). The cleavage products were analyzed by polyacrylamide gradient slab gel electrophoresis and electron microscopy. HPV DNA was cleaved into two fragments by EcoRI (87% and 13% of the genome) and into six fragments, ranging in size from 33.5 to 1.2% of the genome, by Hind endonucleases. The six Hind fragments result from the cleavage of three sequences recognized by HindII, two of which are also cleaved by HpaI, and of three sequence recognized by HindIII. The order of these fragments was determined by comparing their size with that of the fragments obtained with HindII, HindIII, HpaI, and the mixture of HindIII + Hpal. The two EcoRI cleavage sites were located on two adjacent Hind fragments and one of these sites has been taken for the zero point to construct a physical map. The treatment of superhelical HPV DNA with bacteriophage T4 gene 32 protein yields circular structures with a denaturation loop. The cleavage of these complexes with EcoRI and HindIII has shown two easily denatured regions which were located on the cleavage map.", "contents": "Human papillomavirus DNA: physical map. Human papillomavirus (HPV) DNA form I (supercoiled) was prepared from plantar warts. HPV DNA was cleaved with restriction enzymes obtained from the following sources: escherichia coli (EcoRI), Hemophilus influenzae strain Rd (both unfractionated Hind and aeparated HindII and HindIII enzymes) and Hemophilus parainfluenzae (HpaI). The cleavage products were analyzed by polyacrylamide gradient slab gel electrophoresis and electron microscopy. HPV DNA was cleaved into two fragments by EcoRI (87% and 13% of the genome) and into six fragments, ranging in size from 33.5 to 1.2% of the genome, by Hind endonucleases. The six Hind fragments result from the cleavage of three sequences recognized by HindII, two of which are also cleaved by HpaI, and of three sequence recognized by HindIII. The order of these fragments was determined by comparing their size with that of the fragments obtained with HindII, HindIII, HpaI, and the mixture of HindIII + Hpal. The two EcoRI cleavage sites were located on two adjacent Hind fragments and one of these sites has been taken for the zero point to construct a physical map. The treatment of superhelical HPV DNA with bacteriophage T4 gene 32 protein yields circular structures with a denaturation loop. The cleavage of these complexes with EcoRI and HindIII has shown two easily denatured regions which were located on the cleavage map."} {"id": "PMID:174078", "title": "Association of a cyclic AMP-dependent protein kinase with a purified translational inhibitor isolated from hemin-deficient rabbit reticulocyte lysates.", "content": "In the absence of added hemin, protein synthesis in rabbit reticulocyte lysates proceeds at maximal linear rates for several minutes and then ceases abruptly. Inhibition involves the action of a translational inhibitor whose formation is regulated by hemin. Addition of the isolated inhibitor to hemin-supplemented lysates produces an inhibition of protein chain initiation similar to that observed in heme-deficiency. The inhibitor has been purified over 300-fold and contains a protein kinase activity that copurifies with the inhibitory function. With calf thymus histone II as the phosphate receptor, the inhibitor-associated protein kinase requires ATP as the phosphorylating agent. Cycle AMP stimulates kinase activity 5- to 8-fold; the concentration of cycle AMP required for halfmaximal activity is 4 X 10-8 M. Preincubation of the inhibitor in the presence of cyclic AMP significantly reduces cyclic AMP-dependent phosphorylation and inhibitory activity. The corresponding protein kinase activity from hemin-supplemented lysates displays reduced cyclic AMP-dependency and little or no inhibitory activity. These findings suggest that the protein kinase activity associated with the purified translational inhibitor is involved in the mechanism of inhibition of initiation observed in hemedeficient reticulocyte lysates.", "contents": "Association of a cyclic AMP-dependent protein kinase with a purified translational inhibitor isolated from hemin-deficient rabbit reticulocyte lysates. In the absence of added hemin, protein synthesis in rabbit reticulocyte lysates proceeds at maximal linear rates for several minutes and then ceases abruptly. Inhibition involves the action of a translational inhibitor whose formation is regulated by hemin. Addition of the isolated inhibitor to hemin-supplemented lysates produces an inhibition of protein chain initiation similar to that observed in heme-deficiency. The inhibitor has been purified over 300-fold and contains a protein kinase activity that copurifies with the inhibitory function. With calf thymus histone II as the phosphate receptor, the inhibitor-associated protein kinase requires ATP as the phosphorylating agent. Cycle AMP stimulates kinase activity 5- to 8-fold; the concentration of cycle AMP required for halfmaximal activity is 4 X 10-8 M. Preincubation of the inhibitor in the presence of cyclic AMP significantly reduces cyclic AMP-dependent phosphorylation and inhibitory activity. The corresponding protein kinase activity from hemin-supplemented lysates displays reduced cyclic AMP-dependency and little or no inhibitory activity. These findings suggest that the protein kinase activity associated with the purified translational inhibitor is involved in the mechanism of inhibition of initiation observed in hemedeficient reticulocyte lysates."} {"id": "PMID:174079", "title": "Determination of the number of superhelical turns in simian virus 40 DNA by gel electrophoresis.", "content": "Closed-circular, superhelical DNA from simian virus 40 (SV40 DNA I) was treated with an excess of DNA-relaxing enzyme in the presence of increasing amounts of ethidium bromide (EtdBr). After removal of the ethidium, each sample consisted of a group of close-circular DNA molecules differing in their number of superhelical turns (tau) around a mean value of tau in a Gaussian-like distribution. The DNA samples were analyzed by electrophoresis in agarose gels under conditions where the electrophoretic mobility was a function of the number of superhelical turns. Since the distributions around tau of DNA molecules of different samples overlappped, the difference in the mean number of superhelical turns from sample to sample, delta tau, could be determined and used to measure the mean number (tau) for native SV40 DNA I. By this criterion, SV40 DNA I contains a Gaussian-like distribution of molecules differing by integral numbers around a mean value of tau = -24 +/- 2 at 37 degree C [in 0.2 M NaC1, 10 mM Tris-HC1 (pH 7.9), and 0.2 mM EDTA]. The heterogeneity in tau is probably a consequence of thermal fluctuations in the DNA helix at the time when the last phospholiester bond is closed in vivo. When correlated to the buoyant shift of completely relaxed SV40 DNA in a CsC1-propidium diiodide gradient, the number of delta tau = 24 +/- 2 of superhelical versus relaxed DNA implies an unwinding of the DNA helix by 26-28 degree upon intercalation of one molecule of EtdBr.", "contents": "Determination of the number of superhelical turns in simian virus 40 DNA by gel electrophoresis. Closed-circular, superhelical DNA from simian virus 40 (SV40 DNA I) was treated with an excess of DNA-relaxing enzyme in the presence of increasing amounts of ethidium bromide (EtdBr). After removal of the ethidium, each sample consisted of a group of close-circular DNA molecules differing in their number of superhelical turns (tau) around a mean value of tau in a Gaussian-like distribution. The DNA samples were analyzed by electrophoresis in agarose gels under conditions where the electrophoretic mobility was a function of the number of superhelical turns. Since the distributions around tau of DNA molecules of different samples overlappped, the difference in the mean number of superhelical turns from sample to sample, delta tau, could be determined and used to measure the mean number (tau) for native SV40 DNA I. By this criterion, SV40 DNA I contains a Gaussian-like distribution of molecules differing by integral numbers around a mean value of tau = -24 +/- 2 at 37 degree C [in 0.2 M NaC1, 10 mM Tris-HC1 (pH 7.9), and 0.2 mM EDTA]. The heterogeneity in tau is probably a consequence of thermal fluctuations in the DNA helix at the time when the last phospholiester bond is closed in vivo. When correlated to the buoyant shift of completely relaxed SV40 DNA in a CsC1-propidium diiodide gradient, the number of delta tau = 24 +/- 2 of superhelical versus relaxed DNA implies an unwinding of the DNA helix by 26-28 degree upon intercalation of one molecule of EtdBr."} {"id": "PMID:174080", "title": "Partial amino-acid sequence of NAD-specific glutamate dehydrogenase of Neurospora crassa.", "content": "Parts of the primary structure of the NAD-specific glutamate dehydrogenase [L-glutamate:NAD oxidoreductase (deaminating), EC 1.4.1.2] from Neurospora crassa are presented. Segments of the sequence representing 886 unique amino-acid residues have been determined; the largest contains 267 residues. There are only short regions of possible homology between this enzyme and the glutamate dehydrogenases of bovine liver or the NADP-specific enzyme of Neurospora. The large size of the subunit (116,000 molecular weight) of the NAD-specific glutamate dehydrogenase is unusual when compared to other known dehydrogenases.", "contents": "Partial amino-acid sequence of NAD-specific glutamate dehydrogenase of Neurospora crassa. Parts of the primary structure of the NAD-specific glutamate dehydrogenase [L-glutamate:NAD oxidoreductase (deaminating), EC 1.4.1.2] from Neurospora crassa are presented. Segments of the sequence representing 886 unique amino-acid residues have been determined; the largest contains 267 residues. There are only short regions of possible homology between this enzyme and the glutamate dehydrogenases of bovine liver or the NADP-specific enzyme of Neurospora. The large size of the subunit (116,000 molecular weight) of the NAD-specific glutamate dehydrogenase is unusual when compared to other known dehydrogenases."} {"id": "PMID:174081", "title": "In vitro synthesis of full-length DNA transcripts of Rous sarcoma virus RNA by viral DNA polymerase.", "content": "Varying the concentration of Triton X-100, a nonionic detergent used to promote the DNA polymerase activity of Rous sarcoma virus in an endogenous reaction, showed a very sharp peak at about 0.02% (vol/vol) for optimal DNA synthesis. The yield of DNA at this concentration of Triton exceeded yields obtained at concentrations above the optimum by a factor of 2-5 for the 90-min reaction. At optimal Triton concentration, about 1-7% of the DNA made in the absence of actinomycin and about 4-10% of the DNA made in the presence of actinomycin was 2.5 X 10(6) daltons or greater, as estimated by formamide polyacrylamide gel electrophoresis and by alkaline sucrose gradient sedimentation. No large DNA was obtained at higher than optimal Triton concentrations. The large DNA molecules were rendered totally resistant to single-strand specific nuclease S1 after hybridization to an excess of viral RNA. It was concluded that at optimal detergent concentration, the viral DNA polymerase can synthesize full-size DNA transcripts of viral RNA.", "contents": "In vitro synthesis of full-length DNA transcripts of Rous sarcoma virus RNA by viral DNA polymerase. Varying the concentration of Triton X-100, a nonionic detergent used to promote the DNA polymerase activity of Rous sarcoma virus in an endogenous reaction, showed a very sharp peak at about 0.02% (vol/vol) for optimal DNA synthesis. The yield of DNA at this concentration of Triton exceeded yields obtained at concentrations above the optimum by a factor of 2-5 for the 90-min reaction. At optimal Triton concentration, about 1-7% of the DNA made in the absence of actinomycin and about 4-10% of the DNA made in the presence of actinomycin was 2.5 X 10(6) daltons or greater, as estimated by formamide polyacrylamide gel electrophoresis and by alkaline sucrose gradient sedimentation. No large DNA was obtained at higher than optimal Triton concentrations. The large DNA molecules were rendered totally resistant to single-strand specific nuclease S1 after hybridization to an excess of viral RNA. It was concluded that at optimal detergent concentration, the viral DNA polymerase can synthesize full-size DNA transcripts of viral RNA."} {"id": "PMID:174082", "title": "Apoprotein stability and lipid-protein interactions in human plasma high density lipoproteins.", "content": "Temperature-dependent conformational changes of the principal apoprotein of human plasma high density lipoprotein (HDL), apoA-I, have been studied in the isolated apoprotein, in complexes of apoprotein with phospholipid, and in intact HDL. Differential scanning calorimetry shows that in solution apoA-I undergoes a reversible, two-state thermal denaturation (midpoint temperature 54 degrees). The enthalpy (2.4 cal/g)(10.0 J/g) and specific heat change (0.08 cal/degrees C per g)(0.33 J/degrees C per g) associated with the denaturation were used to calculate the free energy difference (deltaG) between native and unfolded apoA-I at 37 degrees. DeltaG (2.4 kcal/mol)(10.0 kJ/mol) is less than that of other globular proteins (typically 8-14 kcal/mol)(33-59 kJ/mol), indicating that at 37 degrees native apoA-I has a loosely folded conformation. Turbidity studies show that apoA-I is able to solubilize phospholipid in its native but not in its denatured form. Mixtures of apo-HDL (the total apoprotein of HDL) or apoA-I with dimyristoyl lecithin show a thermal transition at about 85 degrees not present in the lecithin or the apoprotein alone, which indicates that the native conformation of the apoprotein is stabilized by phospholipid. Scanning calorimetry of intact HDL shows a high-temperature endotherm associated with disruption of the HDL particle, suggesting that in HDL the conformation of apoA-I is also stabilized by interaction with lipid. The loosely folded conformation of native, uncomplexed apoA-I may be especially adapted to the binding of lipid, since this process may involve both hydrophobic sites on the surface of the protein and concealed apolar amino acid residues that are exposed by a cooperative, low energy unfolding process.", "contents": "Apoprotein stability and lipid-protein interactions in human plasma high density lipoproteins. Temperature-dependent conformational changes of the principal apoprotein of human plasma high density lipoprotein (HDL), apoA-I, have been studied in the isolated apoprotein, in complexes of apoprotein with phospholipid, and in intact HDL. Differential scanning calorimetry shows that in solution apoA-I undergoes a reversible, two-state thermal denaturation (midpoint temperature 54 degrees). The enthalpy (2.4 cal/g)(10.0 J/g) and specific heat change (0.08 cal/degrees C per g)(0.33 J/degrees C per g) associated with the denaturation were used to calculate the free energy difference (deltaG) between native and unfolded apoA-I at 37 degrees. DeltaG (2.4 kcal/mol)(10.0 kJ/mol) is less than that of other globular proteins (typically 8-14 kcal/mol)(33-59 kJ/mol), indicating that at 37 degrees native apoA-I has a loosely folded conformation. Turbidity studies show that apoA-I is able to solubilize phospholipid in its native but not in its denatured form. Mixtures of apo-HDL (the total apoprotein of HDL) or apoA-I with dimyristoyl lecithin show a thermal transition at about 85 degrees not present in the lecithin or the apoprotein alone, which indicates that the native conformation of the apoprotein is stabilized by phospholipid. Scanning calorimetry of intact HDL shows a high-temperature endotherm associated with disruption of the HDL particle, suggesting that in HDL the conformation of apoA-I is also stabilized by interaction with lipid. The loosely folded conformation of native, uncomplexed apoA-I may be especially adapted to the binding of lipid, since this process may involve both hydrophobic sites on the surface of the protein and concealed apolar amino acid residues that are exposed by a cooperative, low energy unfolding process."} {"id": "PMID:174083", "title": "Chemically induced dynamic electron polarization in chloroplasts at room temperature: evidence for triplet state participation in photosynthesis.", "content": "A transient electron paramagnetic resonance emission is observed after flash excitation of chloroplasts at room temperature. The spectrum of the emission signal is centered at g = 2.0037 and has a linewidth deltaHpp = 4G (4 X 10(-4) tesla). Inhibitor studies and chemical oxidation indicate that the signal is associated with Photosystem I, but the spectrum and kinetics indicate that it is neither P700 nor an iron-sulfur protein. The emission signal rises with the 2-musec time response of the instrument, and decays during the actinic flash. The emission signal is produced on only the first of a pair of strong flashes separated by 100 musec, indicating that the precursor has not been regenerated in that time. The results are discussed with reference to the two currently accepted mechanisms for chemically induced dynamic electron polarization: the radical pair and the photochemical triplet. For several reasons the photochemical triplet mechanism is the more attractive of the two. It is suggested that at room temperature the primary photochemistry of photosystem I proceeds via a triplet state of chlorophyll, and that the species giving rise to the emission signal is the primary electron acceptor of Photosystem I.", "contents": "Chemically induced dynamic electron polarization in chloroplasts at room temperature: evidence for triplet state participation in photosynthesis. A transient electron paramagnetic resonance emission is observed after flash excitation of chloroplasts at room temperature. The spectrum of the emission signal is centered at g = 2.0037 and has a linewidth deltaHpp = 4G (4 X 10(-4) tesla). Inhibitor studies and chemical oxidation indicate that the signal is associated with Photosystem I, but the spectrum and kinetics indicate that it is neither P700 nor an iron-sulfur protein. The emission signal rises with the 2-musec time response of the instrument, and decays during the actinic flash. The emission signal is produced on only the first of a pair of strong flashes separated by 100 musec, indicating that the precursor has not been regenerated in that time. The results are discussed with reference to the two currently accepted mechanisms for chemically induced dynamic electron polarization: the radical pair and the photochemical triplet. For several reasons the photochemical triplet mechanism is the more attractive of the two. It is suggested that at room temperature the primary photochemistry of photosystem I proceeds via a triplet state of chlorophyll, and that the species giving rise to the emission signal is the primary electron acceptor of Photosystem I."} {"id": "PMID:174084", "title": "Primary charge separation in bacterial photosynthesis: oxidized chlorophylls and reduced pheophytin.", "content": "Bacteriopheophytin, the magnesium-free base of bacteriochlorophyll, undergoes reversible one-electron reduction in organic solvents to yield an anionic free radical with characteristic optical and electron spin resonance spectra. The reduction potential of bacteriopheophytin, E1/2 approximately --0.55 V against a normal hydrogen electrode, compared to E1/2 approximately --0.85 V for bacteriochlorophyll, renders it a likely electron acceptor in the primary charge separation of photosynthesis. Comparison of these data with picosecond optical changes recently observed upon pulsed laser excitation of bacterial reaction centers leads us to propose that bacteriopheophytin is indeed a transient electron acceptor and that the primary charge separation of bacterial photosynthesis occurs between the bacteriochlorophyll complex P870 and bacteriopheophytin to yield the radicals of the oxidized chlorophyll dimer cation and reduced pheophytin anion.", "contents": "Primary charge separation in bacterial photosynthesis: oxidized chlorophylls and reduced pheophytin. Bacteriopheophytin, the magnesium-free base of bacteriochlorophyll, undergoes reversible one-electron reduction in organic solvents to yield an anionic free radical with characteristic optical and electron spin resonance spectra. The reduction potential of bacteriopheophytin, E1/2 approximately --0.55 V against a normal hydrogen electrode, compared to E1/2 approximately --0.85 V for bacteriochlorophyll, renders it a likely electron acceptor in the primary charge separation of photosynthesis. Comparison of these data with picosecond optical changes recently observed upon pulsed laser excitation of bacterial reaction centers leads us to propose that bacteriopheophytin is indeed a transient electron acceptor and that the primary charge separation of bacterial photosynthesis occurs between the bacteriochlorophyll complex P870 and bacteriopheophytin to yield the radicals of the oxidized chlorophyll dimer cation and reduced pheophytin anion."} {"id": "PMID:174085", "title": "Failure of human cells transformed by simian virus 40 to form tumors in athymic nude mice.", "content": "Four individual lines and one subline of human cells, permanently established in tissue culture after infection with simian virus 40, failed to form tumors when inoculated into athymic nude mice. Under identical conditions, three established human cell lines of neoplastic origin and a spontaneously established human lymphocyte line formed tumors. Nude mice that failed to grow tumors from inocula of simian virus 40-transformed human cells, grew tumors from subsequent injections of authentic human cancer cells. Further efforts to demonstrate an immunologic basis for the growth suppression of human simian virus 40 transformants were also negative. The data suggest that the changes in morphology and in vitro growth behavior induced by the viral information are not sufficient for, or are only coincidentally related to, the neoplastic state.", "contents": "Failure of human cells transformed by simian virus 40 to form tumors in athymic nude mice. Four individual lines and one subline of human cells, permanently established in tissue culture after infection with simian virus 40, failed to form tumors when inoculated into athymic nude mice. Under identical conditions, three established human cell lines of neoplastic origin and a spontaneously established human lymphocyte line formed tumors. Nude mice that failed to grow tumors from inocula of simian virus 40-transformed human cells, grew tumors from subsequent injections of authentic human cancer cells. Further efforts to demonstrate an immunologic basis for the growth suppression of human simian virus 40 transformants were also negative. The data suggest that the changes in morphology and in vitro growth behavior induced by the viral information are not sufficient for, or are only coincidentally related to, the neoplastic state."} {"id": "PMID:174086", "title": "Cytoplasmic microtubules in normal and transformed cells in culture: analysis by tubulin antibody immunofluorescence.", "content": "Monospecific antibody directed against bovine brain tubulin was used as an immunofluorescent probe to evaluate the distribution of microtubules in normal and transformed cells grown in tissue culture. The fluorescent staining pattern of transformed and nontransformed cells is significantly different and may be used in conjunction with other morphological features to identify transformants in mixed cell populations. Normal cells are flattened, elongated, and fibroblastic; they display numerous Colcemid-sensitive fluorescent cytoplasmic filaments, presumably microtubules. Transformed cells, however, are smaller, more polygonal in shape, and contain very few cytoplasmic tubules. During mistosis the cytoplasmic microtubule complex of normal cells completely disappears, but reappears after cell division. Treatment of transformed cells with dibutyry-adenosine 3':5'-cyclic monophosphate plus testosterone or theophylline restores the normal fibroblastic appearance of the cells and stimulates the assembly of numerous cytoplasmic microtubules. This study provides further evidence for two separate microtubule entities in cycling nontransformed cells: a cytoplasmic microtubule complex and the microtubules of the mitotic spindle. Although an interchange of tubulin dimers seems to exist between microtubules in the two systems, control of tubule assembly may be under separate constraints. Stimulation of cytoplasmic microtuble assembly in transformed cells by derivatives of adenosine 3':5'-cycle monophosphate suggests that impairment of the cytoplasmic microtubule complex in these cells may be due to suboptimal levels of adenosine 3':5'-cyclic monophosphate.", "contents": "Cytoplasmic microtubules in normal and transformed cells in culture: analysis by tubulin antibody immunofluorescence. Monospecific antibody directed against bovine brain tubulin was used as an immunofluorescent probe to evaluate the distribution of microtubules in normal and transformed cells grown in tissue culture. The fluorescent staining pattern of transformed and nontransformed cells is significantly different and may be used in conjunction with other morphological features to identify transformants in mixed cell populations. Normal cells are flattened, elongated, and fibroblastic; they display numerous Colcemid-sensitive fluorescent cytoplasmic filaments, presumably microtubules. Transformed cells, however, are smaller, more polygonal in shape, and contain very few cytoplasmic tubules. During mistosis the cytoplasmic microtubule complex of normal cells completely disappears, but reappears after cell division. Treatment of transformed cells with dibutyry-adenosine 3':5'-cyclic monophosphate plus testosterone or theophylline restores the normal fibroblastic appearance of the cells and stimulates the assembly of numerous cytoplasmic microtubules. This study provides further evidence for two separate microtubule entities in cycling nontransformed cells: a cytoplasmic microtubule complex and the microtubules of the mitotic spindle. Although an interchange of tubulin dimers seems to exist between microtubules in the two systems, control of tubule assembly may be under separate constraints. Stimulation of cytoplasmic microtuble assembly in transformed cells by derivatives of adenosine 3':5'-cycle monophosphate suggests that impairment of the cytoplasmic microtubule complex in these cells may be due to suboptimal levels of adenosine 3':5'-cyclic monophosphate."} {"id": "PMID:174087", "title": "Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells.", "content": "A rat hepatoma cell line in tissue culture (HTC cells) was treated with hypophyseal extracts from adult male and female rats. Cell homogenates were then assayed for steroid metabolizing enzymes using 4-androsten-3,17-dione as substrate. The major products were the 5 alpha-reduced derivatives (5 alpha-androstane-3,17-dione, androsterone, and epiandrosterone). When the cells were grown in the presence of female hypophyseal extract the apparent activity of the 5 alpha-reductase increased markedly, whereas treatment with male hypophyseal extract was without effect. Treatment with female hypophyseal extract resulted in a marked decrease in the apparent Km for 5 alpha-reductase from 667 +/- 102 to 99 +/- 4 muM in addition to a decrease in the apparent Vmax from 67 +/- 12 to 46 +/- 2 pmol of product/min per mg of protein. A logarithmic dose-response was obtained with female hypophyseal extract. Treatment of the HTC cells with purified rat hypophyseal follicle-stimulating hormone, luteinizing hormone, growth hormone, thyrotropic hormone, and prolactin had only marginal effects on 5 alpha-reductase activity. Crude female hypophyseal extracts were at least 6-fold more potent than any of the standard hormone preparations and at least 250-fold more potent than male hypophyseal extracts when based on activity per mg of pituitary tissue. Chromatography of crude female hypophyseal extracts on Sephadex G-25 indicated that the factor was of high molecular weight. The identity of this activity with a hypophyseal \"feminizing\" factor is postulated.", "contents": "Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells. A rat hepatoma cell line in tissue culture (HTC cells) was treated with hypophyseal extracts from adult male and female rats. Cell homogenates were then assayed for steroid metabolizing enzymes using 4-androsten-3,17-dione as substrate. The major products were the 5 alpha-reduced derivatives (5 alpha-androstane-3,17-dione, androsterone, and epiandrosterone). When the cells were grown in the presence of female hypophyseal extract the apparent activity of the 5 alpha-reductase increased markedly, whereas treatment with male hypophyseal extract was without effect. Treatment with female hypophyseal extract resulted in a marked decrease in the apparent Km for 5 alpha-reductase from 667 +/- 102 to 99 +/- 4 muM in addition to a decrease in the apparent Vmax from 67 +/- 12 to 46 +/- 2 pmol of product/min per mg of protein. A logarithmic dose-response was obtained with female hypophyseal extract. Treatment of the HTC cells with purified rat hypophyseal follicle-stimulating hormone, luteinizing hormone, growth hormone, thyrotropic hormone, and prolactin had only marginal effects on 5 alpha-reductase activity. Crude female hypophyseal extracts were at least 6-fold more potent than any of the standard hormone preparations and at least 250-fold more potent than male hypophyseal extracts when based on activity per mg of pituitary tissue. Chromatography of crude female hypophyseal extracts on Sephadex G-25 indicated that the factor was of high molecular weight. The identity of this activity with a hypophyseal \"feminizing\" factor is postulated."} {"id": "PMID:174088", "title": "Signal input for a chemotactic response in the cellular slime mold Dictyostelium discoideum.", "content": "Drops with different concentrations of 3':5'-cyclic AMP were deposited at various distances from small populations of Dictyostelium discoideum amoebae, and the distances over which 50% of the amoebae drops reacted positively were determined. The linear regression analysis of a bouble logarithmic plot of distance against concentration gives a straight line with a slope of 1/4.25, which value suggests that the amoebae respond to a spatial gradient of cyclic AMP concentration. The threshold value for the signal is 3.6 X 10(-9) M/mm with a sensitivity of measurement of about 1%. These findings are discussed in relation to our present knowledge of cyclic AMP receptors.", "contents": "Signal input for a chemotactic response in the cellular slime mold Dictyostelium discoideum. Drops with different concentrations of 3':5'-cyclic AMP were deposited at various distances from small populations of Dictyostelium discoideum amoebae, and the distances over which 50% of the amoebae drops reacted positively were determined. The linear regression analysis of a bouble logarithmic plot of distance against concentration gives a straight line with a slope of 1/4.25, which value suggests that the amoebae respond to a spatial gradient of cyclic AMP concentration. The threshold value for the signal is 3.6 X 10(-9) M/mm with a sensitivity of measurement of about 1%. These findings are discussed in relation to our present knowledge of cyclic AMP receptors."} {"id": "PMID:174089", "title": "Selective killing of transformed baby hamster kidney (BHK) cells.", "content": "We report here that certain drugs can protect Syrian baby hamster kidney cells (BHK) in culture against the lethal agents cytosine arabinonucleoside, hydroxyurea, and colcemid. Polyoma virus-transformed BHK cells (PyBHK) are killed under the same conditions. The protective drugs include caffeine and streptovitacin A. Kinetic studies show that these drugs act specifically in G1, and that they shift BHK cells from G1 into the G0 state at the restriction point, similar to the effects of high cell density or serum deprivation. These drugs do not block the growth of PyBHK cells nearly as effectively, consistent with a reduced effectiveness of restriction point control in virus-transformed cells. Consequently, the transformed cells around their cycle and are killed by the cell cycle phase-specific toxic agents, in contrast to the arrested BHK cells. These findings provide a model for studies on differential killing of tumor versus normal cells in vivo.", "contents": "Selective killing of transformed baby hamster kidney (BHK) cells. We report here that certain drugs can protect Syrian baby hamster kidney cells (BHK) in culture against the lethal agents cytosine arabinonucleoside, hydroxyurea, and colcemid. Polyoma virus-transformed BHK cells (PyBHK) are killed under the same conditions. The protective drugs include caffeine and streptovitacin A. Kinetic studies show that these drugs act specifically in G1, and that they shift BHK cells from G1 into the G0 state at the restriction point, similar to the effects of high cell density or serum deprivation. These drugs do not block the growth of PyBHK cells nearly as effectively, consistent with a reduced effectiveness of restriction point control in virus-transformed cells. Consequently, the transformed cells around their cycle and are killed by the cell cycle phase-specific toxic agents, in contrast to the arrested BHK cells. These findings provide a model for studies on differential killing of tumor versus normal cells in vivo."} {"id": "PMID:174090", "title": "Chicken neutrophils: oxidative metabolism in phagocytic cells devoid of myeloperoxidase.", "content": "Polymorphonuclear leukocytes isolated from chicken peritoneal exudates have been found to catalyze cyanide-insensitive stimulation of respiration and the hexose monophosphate shunt upon exposure to heat-inactivated Staphylococcus aureus. However, there was no demonstrable formate oxidation concomitant with phagocytosis in either the presence or absence of exogenous catalase. Moreover, chicken polymorphonuclear leukocytes failed to oxidize scopoletin concomitant with phagocytosis in the presence of horseradish peroxidase. While oxygen uptake was increased 2- to 3-fold by the stimulus of phagocytosis, the oxidation of [1-(14)C]glucose was increased approximately 20-fold. The cells contain two mechanisms, a glutathione reductase-glutathione peroxidase system and an NADPH-NAD+ transhydrogenase, each of which is present in sufficient capacity to accommodate the enhanced shunt activity. Although chicken polymorphonuclear leukocytes were found to possess a substantial capacity to catalyze the cyanide-insensitive oxidation of either NADH or NADPH, the total or specific activities of such processes were not demonstrably affected by phagocytosis.", "contents": "Chicken neutrophils: oxidative metabolism in phagocytic cells devoid of myeloperoxidase. Polymorphonuclear leukocytes isolated from chicken peritoneal exudates have been found to catalyze cyanide-insensitive stimulation of respiration and the hexose monophosphate shunt upon exposure to heat-inactivated Staphylococcus aureus. However, there was no demonstrable formate oxidation concomitant with phagocytosis in either the presence or absence of exogenous catalase. Moreover, chicken polymorphonuclear leukocytes failed to oxidize scopoletin concomitant with phagocytosis in the presence of horseradish peroxidase. While oxygen uptake was increased 2- to 3-fold by the stimulus of phagocytosis, the oxidation of [1-(14)C]glucose was increased approximately 20-fold. The cells contain two mechanisms, a glutathione reductase-glutathione peroxidase system and an NADPH-NAD+ transhydrogenase, each of which is present in sufficient capacity to accommodate the enhanced shunt activity. Although chicken polymorphonuclear leukocytes were found to possess a substantial capacity to catalyze the cyanide-insensitive oxidation of either NADH or NADPH, the total or specific activities of such processes were not demonstrably affected by phagocytosis."} {"id": "PMID:174091", "title": "A structural gene mutation affecting the regulatory subunit of cyclic AMP-dependent protein kinase in mouse lymphoma cells.", "content": "Compared to the wild-type parental line of S49 mouse lymphoma cells, intact cells of a mutant line (kin.A) are 10-fold less sensititive to biologic effects of exogenous cyclic adenosine 3':5'-monophophosphate (cAMP), such as induction of cAMP phosphodiesterase, cell cycle-specific growth inhibition, and cytolysis. The cAMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) activity of kin.A cells exhibits an apparent Ka for activation by cAMP 10-fold greater than that of wild type, and is much more resistant to inactivation by heat. These differences between the wild-type and mutant enzymes persist through a high degree of purification, suggesting a structural alteration in the kin.A holoenzyme. Heterologous reconstitution experiments, using separated R and C subunits of the wild-type and kin.A cAMP-dependent kinases, show that the altered cAMP affinity and thermolability are conferred by the R component of the kin.A enzyme. These results are most consistent with a structural mutation in the kin.A gene coding for the R subunit of cAMP-dependent protein kinase. Evidence for a structural mutation helps to define one mechanism of heritable variation in cultured somatic cells. The phenotype produced by the kin.A structural mutation also greatly strengthens the conslusion that cAMP-dependent protein kinase is essential for cAMP regulation of growth and enzyme induction in intact S49 cells.", "contents": "A structural gene mutation affecting the regulatory subunit of cyclic AMP-dependent protein kinase in mouse lymphoma cells. Compared to the wild-type parental line of S49 mouse lymphoma cells, intact cells of a mutant line (kin.A) are 10-fold less sensititive to biologic effects of exogenous cyclic adenosine 3':5'-monophophosphate (cAMP), such as induction of cAMP phosphodiesterase, cell cycle-specific growth inhibition, and cytolysis. The cAMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) activity of kin.A cells exhibits an apparent Ka for activation by cAMP 10-fold greater than that of wild type, and is much more resistant to inactivation by heat. These differences between the wild-type and mutant enzymes persist through a high degree of purification, suggesting a structural alteration in the kin.A holoenzyme. Heterologous reconstitution experiments, using separated R and C subunits of the wild-type and kin.A cAMP-dependent kinases, show that the altered cAMP affinity and thermolability are conferred by the R component of the kin.A enzyme. These results are most consistent with a structural mutation in the kin.A gene coding for the R subunit of cAMP-dependent protein kinase. Evidence for a structural mutation helps to define one mechanism of heritable variation in cultured somatic cells. The phenotype produced by the kin.A structural mutation also greatly strengthens the conslusion that cAMP-dependent protein kinase is essential for cAMP regulation of growth and enzyme induction in intact S49 cells."} {"id": "PMID:174092", "title": "Virus-specific neutralization by a soluble non-immunoglobulin factor found naturally in normal mouse sera.", "content": "A low-molecular-weight substance found naturally in mouse serum neutralizes mouse xenotropic C-type virus. It has no effect on endogenous ecotropic viruses. This neutralizing factor does not belong to the known immunogloblin classes, and its activity is not associated with the antivirus immunoglobulins that can be detected by radioimmunoprecipitation. Preparations of xenotropic virus absorb out this neutralizing activity in mouse sera. The specificity of this factor for X-tropic virus suggests that it represents a newly recognized type of response of the host to an endogenous virus. Its possible role in the regulation of endogenous C-type viruses is considered.", "contents": "Virus-specific neutralization by a soluble non-immunoglobulin factor found naturally in normal mouse sera. A low-molecular-weight substance found naturally in mouse serum neutralizes mouse xenotropic C-type virus. It has no effect on endogenous ecotropic viruses. This neutralizing factor does not belong to the known immunogloblin classes, and its activity is not associated with the antivirus immunoglobulins that can be detected by radioimmunoprecipitation. Preparations of xenotropic virus absorb out this neutralizing activity in mouse sera. The specificity of this factor for X-tropic virus suggests that it represents a newly recognized type of response of the host to an endogenous virus. Its possible role in the regulation of endogenous C-type viruses is considered."} {"id": "PMID:174093", "title": "Translation of messenger ribonucleic acid from isolated pancreatic islets and human insulinomas.", "content": "RNA preparations from isolated rat pancreatic islets and from human insulinomas were injected into oocytes of Xenopus laevis which were then incubated with [3H]leucine. Acid-ethanol extracts of the oocytes were immunoprecipitated with anti-insulin serum using the double antibody technique. Sodium dodecyl sulfate disc gel electrophoresis of the immunoprecipitates showed the presence of an insulin-displaceable immunoreactive material with a molecular weight of about 18,000 in extracts from oocytes injected with RNA of 9-11 S. This immunoreactive product was not detected in extracts from oocytes injected with buffer or 4-8S RNA or RNA heavier than 11 S. These observations suggest the involvement of a precursor larger than proinsulin in the biosynthesis of insulin.", "contents": "Translation of messenger ribonucleic acid from isolated pancreatic islets and human insulinomas. RNA preparations from isolated rat pancreatic islets and from human insulinomas were injected into oocytes of Xenopus laevis which were then incubated with [3H]leucine. Acid-ethanol extracts of the oocytes were immunoprecipitated with anti-insulin serum using the double antibody technique. Sodium dodecyl sulfate disc gel electrophoresis of the immunoprecipitates showed the presence of an insulin-displaceable immunoreactive material with a molecular weight of about 18,000 in extracts from oocytes injected with RNA of 9-11 S. This immunoreactive product was not detected in extracts from oocytes injected with buffer or 4-8S RNA or RNA heavier than 11 S. These observations suggest the involvement of a precursor larger than proinsulin in the biosynthesis of insulin."} {"id": "PMID:174094", "title": "Energy-dependent binding of dansylgalactoside to the lac carrier protein: direct binding measurements.", "content": "High specific activity 6'-N-[3H]dansyl)aminohexyl 1-thio-beta-D-galactopyranoside (Dns6-Gal) has been synthesized, and its binding to Escherichia coli membrane vesicles measured directly by flow dialysis. With ML 308-225 vesicles containing the lac carrier protein, specific binding is not detected in the absence of D-lactate or reduced phenazine methosulfate. In the presence of these electron donors, binding is observed, and the binding constant and number of binding sites are approximately 4 muM and 1.5 nmol/mg of membrane protein, respectively. These values are in excellent agreement with those obtained by fluorescence titration. p-Chloromercuribenzenesulfonate, which directly inactivates the lac carrier protein, and carbonylcyanide m-chlorophenylhydrazone, which collapses the membrane potential, cause release of bound Dns6-Gal. Moreover, significant binding is not observed with membrane vesicles that are devoid of the lac carrier protein. The results provide qualitative and quantitative confirmation of previous studies which indicate that changes in dansylgalactoside fluorescence observed on \"energization\" of membrane vesicles reflect binding of the probe to the lac carrier protein.", "contents": "Energy-dependent binding of dansylgalactoside to the lac carrier protein: direct binding measurements. High specific activity 6'-N-[3H]dansyl)aminohexyl 1-thio-beta-D-galactopyranoside (Dns6-Gal) has been synthesized, and its binding to Escherichia coli membrane vesicles measured directly by flow dialysis. With ML 308-225 vesicles containing the lac carrier protein, specific binding is not detected in the absence of D-lactate or reduced phenazine methosulfate. In the presence of these electron donors, binding is observed, and the binding constant and number of binding sites are approximately 4 muM and 1.5 nmol/mg of membrane protein, respectively. These values are in excellent agreement with those obtained by fluorescence titration. p-Chloromercuribenzenesulfonate, which directly inactivates the lac carrier protein, and carbonylcyanide m-chlorophenylhydrazone, which collapses the membrane potential, cause release of bound Dns6-Gal. Moreover, significant binding is not observed with membrane vesicles that are devoid of the lac carrier protein. The results provide qualitative and quantitative confirmation of previous studies which indicate that changes in dansylgalactoside fluorescence observed on \"energization\" of membrane vesicles reflect binding of the probe to the lac carrier protein."} {"id": "PMID:174095", "title": "Oxidation of ferrocytochrome c by mitochondrial cytochrome c oxidase.", "content": "Attempts to rationalize the kinetics of cytochrome c oxidation catalyzed by solubilized mitochondrial cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) have been based on assumptions of productive complex formation (Michaelis-Menten approach). However, the range of substrate concentrations used has not, in general, been sufficient to establish a general rate equation. Data adequate to derive such a rate expression are presented, as well as a method for estimation of constants which appear in the rate law deduced and reported herein. It is shown that either of two types of mechanisms, one assuming productive complex formation, as opposed to the other postulating dead-end complex formation, accurately predict the rate equation as deduced from experiment.", "contents": "Oxidation of ferrocytochrome c by mitochondrial cytochrome c oxidase. Attempts to rationalize the kinetics of cytochrome c oxidation catalyzed by solubilized mitochondrial cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) have been based on assumptions of productive complex formation (Michaelis-Menten approach). However, the range of substrate concentrations used has not, in general, been sufficient to establish a general rate equation. Data adequate to derive such a rate expression are presented, as well as a method for estimation of constants which appear in the rate law deduced and reported herein. It is shown that either of two types of mechanisms, one assuming productive complex formation, as opposed to the other postulating dead-end complex formation, accurately predict the rate equation as deduced from experiment."} {"id": "PMID:174096", "title": "Binding, internalization, and degradation of low density lipoprotein by normal human fibroblasts and by fibroblasts from a case of homozygous familial hypercholesterolemia.", "content": "Skin fibroblasts from a patient with homozygous familial hypercholesterolemia (HFH) were compared with normal skin fibroblasts with regard to binding, internalization, and degradation of iodinated human low density lipoprotein (LDL). Like other cell lines from HFH patients, the mutant cells showed no suppression of sterol synthesis by LDL. Surface binding, measured at 0 degrees to eliminate the appreciable internalization that was shown to occur at 37 degrees, was on the average slightly less for HFH cells than normal cells at low LDL concentrations but comparable or even greater at high LDL concentrations (greater than 60 mug of LDL protein per ml). A major defect observed was in the rate of internalization of LDL at 37 degrees, which was only 1-10% of that in normal cells. LDL degradation was also markedly reduced but not to the same extent. Thus, a larger fraction of the LDL taken up appeared to be degraded by the mutant cells. The most striking defect observed, then, was not in surface binding of LDL but in rate of LDL internalization. While this might be secondary to a defect in specific binding sites of LDL, the magnitude of the observed differences in binding at low temperature seems too small to account for the huge differences in internalization (13- to 115-fold).", "contents": "Binding, internalization, and degradation of low density lipoprotein by normal human fibroblasts and by fibroblasts from a case of homozygous familial hypercholesterolemia. Skin fibroblasts from a patient with homozygous familial hypercholesterolemia (HFH) were compared with normal skin fibroblasts with regard to binding, internalization, and degradation of iodinated human low density lipoprotein (LDL). Like other cell lines from HFH patients, the mutant cells showed no suppression of sterol synthesis by LDL. Surface binding, measured at 0 degrees to eliminate the appreciable internalization that was shown to occur at 37 degrees, was on the average slightly less for HFH cells than normal cells at low LDL concentrations but comparable or even greater at high LDL concentrations (greater than 60 mug of LDL protein per ml). A major defect observed was in the rate of internalization of LDL at 37 degrees, which was only 1-10% of that in normal cells. LDL degradation was also markedly reduced but not to the same extent. Thus, a larger fraction of the LDL taken up appeared to be degraded by the mutant cells. The most striking defect observed, then, was not in surface binding of LDL but in rate of LDL internalization. While this might be secondary to a defect in specific binding sites of LDL, the magnitude of the observed differences in binding at low temperature seems too small to account for the huge differences in internalization (13- to 115-fold)."} {"id": "PMID:174097", "title": "Cellular cyclic nucleotides and enzyme secretion in the pancreatic acinar cell.", "content": "Cellular levels of cAMP and cGMP were measured in guinea pig pancreatic lobules incubated in vitro, during basal or stimulated secretion. Stimulation with optimal concentrations of carbamylcholine (carbachol) (10(-5) M), pancreozymin (0.1 unit/ml), and caerulein (10(-9) M) resulted within seconds in a sharp rise in cGMP levels, from five to more than 20 times that of basal levels. cAMP levels did not change significantly. cGMP increases were maximal at 2 min then subsided by 4-7 min to a plateau about two to three times that of basal level. This plateau was maintained for the duration of the secretagogue stimulus. Removal of the carbachol stimulus resulted in a rapid decrease in cGMP levels to that of the basal state. The cellular cGMP levels observed within the first 2 min of stimulation correlated closely with the dose of carbachol and the secretory response. Atropine at 10(-4) M blocked the cGMP elevation due to carbachol but not that due to pancreozymin, while carbonyl cyanide m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation, blocked the response to both secretagogues. Similar though less extensive findings were observed using rabbit pancreatic lobules incubated in vitro. High concentrations (10(-2)-10(-3) M) of the dibutyryl and 8-bromo analogues of both nucleotides were effective, though suboptimal, secretagogues. In the case of the cAMP analogues, the secretory response was associated with a rise in endogenous cGMP levels, similar to that observed during suboptimal carbachol stimulation. These findings suggest that cGMP may be an intracellular mediator in the process of stimulus secretion coupling in the acinar cell of the exocrine pancreas.", "contents": "Cellular cyclic nucleotides and enzyme secretion in the pancreatic acinar cell. Cellular levels of cAMP and cGMP were measured in guinea pig pancreatic lobules incubated in vitro, during basal or stimulated secretion. Stimulation with optimal concentrations of carbamylcholine (carbachol) (10(-5) M), pancreozymin (0.1 unit/ml), and caerulein (10(-9) M) resulted within seconds in a sharp rise in cGMP levels, from five to more than 20 times that of basal levels. cAMP levels did not change significantly. cGMP increases were maximal at 2 min then subsided by 4-7 min to a plateau about two to three times that of basal level. This plateau was maintained for the duration of the secretagogue stimulus. Removal of the carbachol stimulus resulted in a rapid decrease in cGMP levels to that of the basal state. The cellular cGMP levels observed within the first 2 min of stimulation correlated closely with the dose of carbachol and the secretory response. Atropine at 10(-4) M blocked the cGMP elevation due to carbachol but not that due to pancreozymin, while carbonyl cyanide m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation, blocked the response to both secretagogues. Similar though less extensive findings were observed using rabbit pancreatic lobules incubated in vitro. High concentrations (10(-2)-10(-3) M) of the dibutyryl and 8-bromo analogues of both nucleotides were effective, though suboptimal, secretagogues. In the case of the cAMP analogues, the secretory response was associated with a rise in endogenous cGMP levels, similar to that observed during suboptimal carbachol stimulation. These findings suggest that cGMP may be an intracellular mediator in the process of stimulus secretion coupling in the acinar cell of the exocrine pancreas."} {"id": "PMID:174098", "title": "Surface marker characteristics and Epstein-Barr virus studies of two established North American Burkitt's lymphoma cell lines.", "content": "Tumor cell lines have been established in continuous culture from two North American Burkitt's lymphomas. The SU-AmB-1 line, derived from a patient with low serum antibody titers to Epstein-Barr virus (EBV), was devoid of EBV genomes by the reaction for EBV-associated nuclear antigen (EBNA), could not be induced to express EBV antigens, and was highly refractory to EBV superinfection. Conversely, the SU-AmB-2 cell line, derived from a patient with \"African type\" serology, yielded a positive EBNA reaction and was readily inducible and superinfectable. Although both cell lines possessed B (bone-marrow-derived) cell characteristics, they had different surface marker patterns. It is postulated that two different classes of undifferentiated B cell lymphomas exist, one of which is positive for the presence of EBV genomes and occurs endemically in Africa and New Guinea and sporadically in other parts of the world, the other of which is EBV-negative and occurs sporadically throughout the world, including the endemic areas.", "contents": "Surface marker characteristics and Epstein-Barr virus studies of two established North American Burkitt's lymphoma cell lines. Tumor cell lines have been established in continuous culture from two North American Burkitt's lymphomas. The SU-AmB-1 line, derived from a patient with low serum antibody titers to Epstein-Barr virus (EBV), was devoid of EBV genomes by the reaction for EBV-associated nuclear antigen (EBNA), could not be induced to express EBV antigens, and was highly refractory to EBV superinfection. Conversely, the SU-AmB-2 cell line, derived from a patient with \"African type\" serology, yielded a positive EBNA reaction and was readily inducible and superinfectable. Although both cell lines possessed B (bone-marrow-derived) cell characteristics, they had different surface marker patterns. It is postulated that two different classes of undifferentiated B cell lymphomas exist, one of which is positive for the presence of EBV genomes and occurs endemically in Africa and New Guinea and sporadically in other parts of the world, the other of which is EBV-negative and occurs sporadically throughout the world, including the endemic areas."} {"id": "PMID:174099", "title": "Antigen related to mammalian type-C RNA viral p30 proteins is located in renal glomeruli in human systemic lupus erythematosus.", "content": "An antigen related to mammalian type-C RNA viral p30 proteins was shown by the use of anti-p30 sera and the indirect immunofluorescence method to be present in the kidneys and spleen in a fulminant fatal case of human systemic lupus erythematosus and to be located in the glomeruli, the site of active lupus diffuse glomerulonephritis.", "contents": "Antigen related to mammalian type-C RNA viral p30 proteins is located in renal glomeruli in human systemic lupus erythematosus. An antigen related to mammalian type-C RNA viral p30 proteins was shown by the use of anti-p30 sera and the indirect immunofluorescence method to be present in the kidneys and spleen in a fulminant fatal case of human systemic lupus erythematosus and to be located in the glomeruli, the site of active lupus diffuse glomerulonephritis."} {"id": "PMID:174100", "title": "A ribosome-dependent GTPase from yeast distinct from elongation factor 2.", "content": "Three proteins required for poly(U)-directed polyphenylalanine synthesis have been separated from yeast. Two of the factors correspond to the elongation factors 1 and 2 described for other eukaryotic systems, according to the criteria of phenylalanyl-tRNA binding and diphtheria toxin-catalyzed ADP-ribosylation. The third protein, while absolutely required for polyphenylalanine synthesis, was a more active ribosome-dependent GTPase than elongation factor 2.", "contents": "A ribosome-dependent GTPase from yeast distinct from elongation factor 2. Three proteins required for poly(U)-directed polyphenylalanine synthesis have been separated from yeast. Two of the factors correspond to the elongation factors 1 and 2 described for other eukaryotic systems, according to the criteria of phenylalanyl-tRNA binding and diphtheria toxin-catalyzed ADP-ribosylation. The third protein, while absolutely required for polyphenylalanine synthesis, was a more active ribosome-dependent GTPase than elongation factor 2."} {"id": "PMID:174101", "title": "Fluorescence-detected magnetic circular dichroism of fluorescent and nonfluorescent molecules.", "content": "We have modified a spectrometer for the measurement of fluorescence-detected magnetic (and natural) circular dichroism (FDMCD). The instrument can be operated either in a direct mode in which the average and polarization-induced differential fluorescent intensities are recorded separately or in a mode which records their ratio. We have measured the FDMCD of tryptophan, which is itself fluorescent. With the aid of an added fluorescent molecule we also measured the FDMCD of Fe(III) cytochrome c, which is nonfluorescent. In both cases, the FDMCD agreed with the conventional transmission-detected magnetic circular dichroism within experimental uncertainty. The FDMCD of both fluorescent and nonfluorescent molecules is potentially a useful technique for investigating optically dense materials and biological molecules in their native environments and systems in which there is inter- or intramolecular energy transfer.", "contents": "Fluorescence-detected magnetic circular dichroism of fluorescent and nonfluorescent molecules. We have modified a spectrometer for the measurement of fluorescence-detected magnetic (and natural) circular dichroism (FDMCD). The instrument can be operated either in a direct mode in which the average and polarization-induced differential fluorescent intensities are recorded separately or in a mode which records their ratio. We have measured the FDMCD of tryptophan, which is itself fluorescent. With the aid of an added fluorescent molecule we also measured the FDMCD of Fe(III) cytochrome c, which is nonfluorescent. In both cases, the FDMCD agreed with the conventional transmission-detected magnetic circular dichroism within experimental uncertainty. The FDMCD of both fluorescent and nonfluorescent molecules is potentially a useful technique for investigating optically dense materials and biological molecules in their native environments and systems in which there is inter- or intramolecular energy transfer."} {"id": "PMID:174102", "title": "5'-terminal structure of poliovirus polyribosomal RNA is pUp.", "content": "Poliovirus RNA purified from virus-specific polyribosomes does not contain m7G in a 5'-5'-pyrophosphate linkage at its 5'-end. The only potential 5'-end found in ribonuclease digests of this RNA is pUp, which is present in a yield of 1 mole/mole of poliovirus RNA. We conclude that a 5'-terminal m7G is not required for translation of at least one RNA species in animal cells.", "contents": "5'-terminal structure of poliovirus polyribosomal RNA is pUp. Poliovirus RNA purified from virus-specific polyribosomes does not contain m7G in a 5'-5'-pyrophosphate linkage at its 5'-end. The only potential 5'-end found in ribonuclease digests of this RNA is pUp, which is present in a yield of 1 mole/mole of poliovirus RNA. We conclude that a 5'-terminal m7G is not required for translation of at least one RNA species in animal cells."} {"id": "PMID:174103", "title": "Regulation of transsynaptically elicited increase of 3':5'-cyclic AMP by endogenous phosphodiesterase activator.", "content": "Experiments with cold exposure confirmed previous studies indicating that the endogenous protein acitvator of phosphodiesterase (PDEA) isolated by Cheung participates in the in vivo regulation of 3':5'-cyclic adenosine monophosphate (cAMP) in adrenal medulla. This activator of cAMP phosphodiesterase (PDE) (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) is present in the particulate as well as the soluble fractions of rat brain. It was found that a purified cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37), in the presence of ATP and cAMP, stimulates 3-fold the release of PDEA from the particulate fraction of rat brain and adrenal medulla. The substrate for this phosphorylation could be either a membrane protein that binds PDEA or PDEA itself. In vivo evidence, however, obtained by injecting rats intraventricularly with [gamma-32P]ATP, indicates that the PDEA does not contain radioactive phosphate in its structure. Also, PDEA could not be phosphorylated by protein kinase in vitro. The following mechanism is postulated: when the intracellular content of cAMP increases it activates a protein kinase which phosphorylates a PDEA-binding membrane protein and releases PDEA. In turn this binds to activator-deficient high Km PDE and decreases its Km to facilitate the hydrolysis of the increased concentration of cAMP.", "contents": "Regulation of transsynaptically elicited increase of 3':5'-cyclic AMP by endogenous phosphodiesterase activator. Experiments with cold exposure confirmed previous studies indicating that the endogenous protein acitvator of phosphodiesterase (PDEA) isolated by Cheung participates in the in vivo regulation of 3':5'-cyclic adenosine monophosphate (cAMP) in adrenal medulla. This activator of cAMP phosphodiesterase (PDE) (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) is present in the particulate as well as the soluble fractions of rat brain. It was found that a purified cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37), in the presence of ATP and cAMP, stimulates 3-fold the release of PDEA from the particulate fraction of rat brain and adrenal medulla. The substrate for this phosphorylation could be either a membrane protein that binds PDEA or PDEA itself. In vivo evidence, however, obtained by injecting rats intraventricularly with [gamma-32P]ATP, indicates that the PDEA does not contain radioactive phosphate in its structure. Also, PDEA could not be phosphorylated by protein kinase in vitro. The following mechanism is postulated: when the intracellular content of cAMP increases it activates a protein kinase which phosphorylates a PDEA-binding membrane protein and releases PDEA. In turn this binds to activator-deficient high Km PDE and decreases its Km to facilitate the hydrolysis of the increased concentration of cAMP."} {"id": "PMID:174104", "title": "Binding of Cibacron blue F3GA to proteins containing the dinucleotide fold.", "content": "A simple, convenient, and sensitive spectrophotometric procedure is described for quantitative measurement of nucleoside phosphate binding sites constructed by the dinucleotide fold. The procedure involves difference spectral titration of such enzymes with the dye Cibacron blue F3GA in a spectral region remote from the intrinsic absorbance of proteins or natural ligands. The titration curves can be analyzed to determine the affinity of nucleoside phosphate binding sites for both the dye and the natural ligand over a potentially wide range of experimental conditions. The interaction of the dye with two proteins which contain the dinucleotide fold, lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), is illustrated.", "contents": "Binding of Cibacron blue F3GA to proteins containing the dinucleotide fold. A simple, convenient, and sensitive spectrophotometric procedure is described for quantitative measurement of nucleoside phosphate binding sites constructed by the dinucleotide fold. The procedure involves difference spectral titration of such enzymes with the dye Cibacron blue F3GA in a spectral region remote from the intrinsic absorbance of proteins or natural ligands. The titration curves can be analyzed to determine the affinity of nucleoside phosphate binding sites for both the dye and the natural ligand over a potentially wide range of experimental conditions. The interaction of the dye with two proteins which contain the dinucleotide fold, lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), is illustrated."} {"id": "PMID:174105", "title": "\"Early\" simian-virus-40-specific RNA contains information for tumor antigen formation and chromatin replication.", "content": "Simian virus 40 (SV40) induces tumor (T)-antigen formation, chromatin replication, and mitosis in primary mouse kidney cells arrested in G0 phase of the mitotic cycle. The temporal and quantitative relation between these early virus-specific reactions led to the hypothesis that the early SV40 mRNA contains information necessary for T-antigen formation and induction of cellular DNA synthesis. To get direct experimental evidence for this hypothesis, the early strand of SV40 DNA was transcribed in vitro by Escherichia coli DNA-dependent RNA polymerase and the SV40-specific cRNA was transferred by microinjection into epitheloid cells of confluent primary mouse kidney cultures. T-antigen formation and stimulation of DNA synthesis were investigated in the recipient cells. The experimental results obtained agree with the hypothesis that T-antigen is a virus-coded protein and that the early virus-specific mRNA contains information necessary for stimulation of cellular DNA replication in the arrested cells.", "contents": "\"Early\" simian-virus-40-specific RNA contains information for tumor antigen formation and chromatin replication. Simian virus 40 (SV40) induces tumor (T)-antigen formation, chromatin replication, and mitosis in primary mouse kidney cells arrested in G0 phase of the mitotic cycle. The temporal and quantitative relation between these early virus-specific reactions led to the hypothesis that the early SV40 mRNA contains information necessary for T-antigen formation and induction of cellular DNA synthesis. To get direct experimental evidence for this hypothesis, the early strand of SV40 DNA was transcribed in vitro by Escherichia coli DNA-dependent RNA polymerase and the SV40-specific cRNA was transferred by microinjection into epitheloid cells of confluent primary mouse kidney cultures. T-antigen formation and stimulation of DNA synthesis were investigated in the recipient cells. The experimental results obtained agree with the hypothesis that T-antigen is a virus-coded protein and that the early virus-specific mRNA contains information necessary for stimulation of cellular DNA replication in the arrested cells."} {"id": "PMID:174106", "title": "The 5' end of poliovirus mRNA is not capped with m7G(5')ppp(5')Np.", "content": "Poliovirus was grown in HeLa cells in the presence of phosphorus-32 and actinomycin D. Three to four hours after infection, viral mRNA was recovered from polyribosomes and its identity verified by two-dimensional gel electrophoresis of RNase T1 digests. Digestion of the viral [32P]mRNA with RNase T2 and separation of the products by ion exchange chromatography at pH 5 yielded pUp as possible 5' terminus but no \"capping group\" of the structure m7G(5')ppp(5')Np. Total cytoplasmic [32P]RNA of HeLa cells, on the other hand, was found to contain capping groups. Neither the capping group nor ppNp or pppNp was found in an RNase T2 digest of poliovirion [32P]RNA, in agreement with previous results [Wimmer, E. (1972) J. Mol. Biol. 68, 537-540]. The data indicate that 5'-terminal m7G(5')ppp(5')Np is absent from poliovirus RNAs and, therefore, is not involved in poliovirus protein synthesis.", "contents": "The 5' end of poliovirus mRNA is not capped with m7G(5')ppp(5')Np. Poliovirus was grown in HeLa cells in the presence of phosphorus-32 and actinomycin D. Three to four hours after infection, viral mRNA was recovered from polyribosomes and its identity verified by two-dimensional gel electrophoresis of RNase T1 digests. Digestion of the viral [32P]mRNA with RNase T2 and separation of the products by ion exchange chromatography at pH 5 yielded pUp as possible 5' terminus but no \"capping group\" of the structure m7G(5')ppp(5')Np. Total cytoplasmic [32P]RNA of HeLa cells, on the other hand, was found to contain capping groups. Neither the capping group nor ppNp or pppNp was found in an RNase T2 digest of poliovirion [32P]RNA, in agreement with previous results [Wimmer, E. (1972) J. Mol. Biol. 68, 537-540]. The data indicate that 5'-terminal m7G(5')ppp(5')Np is absent from poliovirus RNAs and, therefore, is not involved in poliovirus protein synthesis."} {"id": "PMID:174107", "title": "Order of transcription of genes of vesicular stomatitis virus.", "content": "The effect of ultraviolet radiation on the expression of the genes of vesicular stomatitis virus (VSV) was studied in a cell-free system which executed coupled transcription and translation of the viral genes. In this system, which contained detergent-activated virus and a cytoplasmic extract of mouse L-cells, three of the five viral proteins (N, NS, and M) were synthesized accurately and efficiently; a putative precursor to the viral glycoprotein (G) was also made, but synthesis of the L protein was not detected. In response to irradiation of VSV, the synthesis of each protein in the coupled system displayed a characteristic single-hit inhibition. This permitted calculation of the apparent target-sizes for expression of the different viral genes relative to the entire genome (3.6 to 4.0 X 10(6) daltons) as measured by loss of infectivity. These are: N, 0.55 X 10(6); NS, 0.83 X 10(6); M, 1.12 X 10(6); G, 1.76 X 10(6) daltons of RNA. Only the N protein gene has a target-size which corresponds to that predicted from the molecular weight of its messenger RNA (molecular weight: 0.55 X 10(6)). The target-sizes for the other three genes are two to four times larger than expected, and are not proportional to the molecular weights of their corresponding messenger RNAs (molecular weights: NS, 0.28 X 10(6); M, 0.28 X 10(6); G, 0.7 X 10(6)). The polar effect of UV irradiation is inconsistent with independent transcription of each of the genes of VSV. Rather, the target-sizes appear to be cumulative, suggesting that trnascription initiates at a single point on VSV RNA and proceeds in the order 3'-N-NS-M-G-(L)-5'.", "contents": "Order of transcription of genes of vesicular stomatitis virus. The effect of ultraviolet radiation on the expression of the genes of vesicular stomatitis virus (VSV) was studied in a cell-free system which executed coupled transcription and translation of the viral genes. In this system, which contained detergent-activated virus and a cytoplasmic extract of mouse L-cells, three of the five viral proteins (N, NS, and M) were synthesized accurately and efficiently; a putative precursor to the viral glycoprotein (G) was also made, but synthesis of the L protein was not detected. In response to irradiation of VSV, the synthesis of each protein in the coupled system displayed a characteristic single-hit inhibition. This permitted calculation of the apparent target-sizes for expression of the different viral genes relative to the entire genome (3.6 to 4.0 X 10(6) daltons) as measured by loss of infectivity. These are: N, 0.55 X 10(6); NS, 0.83 X 10(6); M, 1.12 X 10(6); G, 1.76 X 10(6) daltons of RNA. Only the N protein gene has a target-size which corresponds to that predicted from the molecular weight of its messenger RNA (molecular weight: 0.55 X 10(6)). The target-sizes for the other three genes are two to four times larger than expected, and are not proportional to the molecular weights of their corresponding messenger RNAs (molecular weights: NS, 0.28 X 10(6); M, 0.28 X 10(6); G, 0.7 X 10(6)). The polar effect of UV irradiation is inconsistent with independent transcription of each of the genes of VSV. Rather, the target-sizes appear to be cumulative, suggesting that trnascription initiates at a single point on VSV RNA and proceeds in the order 3'-N-NS-M-G-(L)-5'."} {"id": "PMID:174108", "title": "Location of envelope-specific and sarcoma-specific oligonucleotides on RNA of Schmidt-Ruppin Rous sarcoma virus.", "content": "Envelope-specific and sarcoma-specific nucleotide sequences have been located within the 10,000 nucleotides of the RNA of nondefective Schmidt-Ruppin Rous sarcoma virus (nd SR). For this purpose, about 30 RNase-T1-resistant oligonucleotides were ordered relative to the 3'-poly(A) terminus of the RNA, to construct an oligonucleotide map of the nd SR RNA. A cluster of seven envelope-specific oligonucleotides, identified by their absence from an otherwise very similar oligonucleotide map of an envelop-defective deletion mutant (which lacks the major viral glycoprotein), mapped at a distance of 2800-5000 nucleotides from the poly(A) end of nd SR RNA. A cluster of two sarcoma-specific oligonucleotides, identified by their absence from an otherwise nearly identical oligonucleotide map of a transformation-defective deletion mutant, mapped at a distance of 1000-2000 nucleotides from the poly(A) end of nd SR RNA. The oligonucleotide maps of nd SR and of the two deletion mutants were the same from the poly(A) end up to 650 nucleotides and included one terminal oligonucleotid, termed C, which is found in all avian tumor viruses tested so far. A possible gene order consistent with our data suggests that sarcoma-specific nucleotide sequences map between envelope-specific nucleotide sequences and the poly(A) end of the RNA.", "contents": "Location of envelope-specific and sarcoma-specific oligonucleotides on RNA of Schmidt-Ruppin Rous sarcoma virus. Envelope-specific and sarcoma-specific nucleotide sequences have been located within the 10,000 nucleotides of the RNA of nondefective Schmidt-Ruppin Rous sarcoma virus (nd SR). For this purpose, about 30 RNase-T1-resistant oligonucleotides were ordered relative to the 3'-poly(A) terminus of the RNA, to construct an oligonucleotide map of the nd SR RNA. A cluster of seven envelope-specific oligonucleotides, identified by their absence from an otherwise very similar oligonucleotide map of an envelop-defective deletion mutant (which lacks the major viral glycoprotein), mapped at a distance of 2800-5000 nucleotides from the poly(A) end of nd SR RNA. A cluster of two sarcoma-specific oligonucleotides, identified by their absence from an otherwise nearly identical oligonucleotide map of a transformation-defective deletion mutant, mapped at a distance of 1000-2000 nucleotides from the poly(A) end of nd SR RNA. The oligonucleotide maps of nd SR and of the two deletion mutants were the same from the poly(A) end up to 650 nucleotides and included one terminal oligonucleotid, termed C, which is found in all avian tumor viruses tested so far. A possible gene order consistent with our data suggests that sarcoma-specific nucleotide sequences map between envelope-specific nucleotide sequences and the poly(A) end of the RNA."} {"id": "PMID:174109", "title": "Primary structure determination of two cytochromes c2: close similarity to functionally unrelated mitochondrial cytochrome C.", "content": "The amino-acid sequences of the cytochromes c2 from the photosynthetic non-sulfur purple bacteria Rhodomicrobium vannielii and Rhodopseudomonas viridis have been determined. Only a single residue deletion (at position 11 in horse cytochrome c) is necessary to align the sequences with those of mitochondrial cytochromes c. The overall sequence similarity between these cytochromes c2 and mitochondrial cytochromes c is closer than that between mitochondrial cytochromes c and the other cytochromes c2 of known sequence, and in the latter multiple insertions and deletions must be postulated before a match can be obtained. Nevertheless, these two cytochromes c2 show no better reactivity with the mitochondrial cytochrome c oxidase than do the less well-matched cytochromes c2. The bearing of these findings on possible evolutionary relationship between mitochondria and prokaryotes is discussed.", "contents": "Primary structure determination of two cytochromes c2: close similarity to functionally unrelated mitochondrial cytochrome C. The amino-acid sequences of the cytochromes c2 from the photosynthetic non-sulfur purple bacteria Rhodomicrobium vannielii and Rhodopseudomonas viridis have been determined. Only a single residue deletion (at position 11 in horse cytochrome c) is necessary to align the sequences with those of mitochondrial cytochromes c. The overall sequence similarity between these cytochromes c2 and mitochondrial cytochromes c is closer than that between mitochondrial cytochromes c and the other cytochromes c2 of known sequence, and in the latter multiple insertions and deletions must be postulated before a match can be obtained. Nevertheless, these two cytochromes c2 show no better reactivity with the mitochondrial cytochrome c oxidase than do the less well-matched cytochromes c2. The bearing of these findings on possible evolutionary relationship between mitochondria and prokaryotes is discussed."} {"id": "PMID:174110", "title": "Mutants of Balb/c 3T3 fibroblasts defective in adhesiveness to substratum: evidence for alteration in cell surface proteins.", "content": "Two mutants of Balb/c 3T3 cells defective in adhesiveness to substratum have been isolated. After exposure to a mutagen a cell population was treated with prostaglandin E1 and methylisobutylxanthine to elevate the cells 3':5'-cyclic AMP levels and adhesion to the substratum; then, loosley adherent cells were harvested by gentle detachment. After four cycles of selection two clones were isolated. Both are characterized by a round morphology and a decreased adhesion to substratum. The defect in adhesion appears to be responsible for the change in cell shape, since the mutant cells become flattened and look similar to wild-type cells when treated with dibutyryl cyclic AMP even though their adhesiveness remains decreased. Further, the surface of both mutants is chemically altered. Lactoperoxidase-catalyzed iodination of the cell surface shows that two iodinated polypeptides (molecular weight, Mr, 90,000 and 135-140,000) present in wild-type cells are not detected on the surface of the mutants, and another iodinated band (110-120,000 Mr) is markedly decreased. In addition, one mutant is also missing the high-molecular-weight (230,000) cell surface protein that is sensitive to transformation. No changes have been found in the content of cyclic AMP or free or polymerized tubulin. The exponential growth rate and saturation density are not altered in these adhesion--eficient cells. This last result suggests that modulation of adhesion to substratum per se does not play an important role in the growth control of Balb/c 3T3 cells in vitro.", "contents": "Mutants of Balb/c 3T3 fibroblasts defective in adhesiveness to substratum: evidence for alteration in cell surface proteins. Two mutants of Balb/c 3T3 cells defective in adhesiveness to substratum have been isolated. After exposure to a mutagen a cell population was treated with prostaglandin E1 and methylisobutylxanthine to elevate the cells 3':5'-cyclic AMP levels and adhesion to the substratum; then, loosley adherent cells were harvested by gentle detachment. After four cycles of selection two clones were isolated. Both are characterized by a round morphology and a decreased adhesion to substratum. The defect in adhesion appears to be responsible for the change in cell shape, since the mutant cells become flattened and look similar to wild-type cells when treated with dibutyryl cyclic AMP even though their adhesiveness remains decreased. Further, the surface of both mutants is chemically altered. Lactoperoxidase-catalyzed iodination of the cell surface shows that two iodinated polypeptides (molecular weight, Mr, 90,000 and 135-140,000) present in wild-type cells are not detected on the surface of the mutants, and another iodinated band (110-120,000 Mr) is markedly decreased. In addition, one mutant is also missing the high-molecular-weight (230,000) cell surface protein that is sensitive to transformation. No changes have been found in the content of cyclic AMP or free or polymerized tubulin. The exponential growth rate and saturation density are not altered in these adhesion--eficient cells. This last result suggests that modulation of adhesion to substratum per se does not play an important role in the growth control of Balb/c 3T3 cells in vitro."} {"id": "PMID:174111", "title": "Effect of Xenopus laevis oocyte extract on supercoiled simian virus 40 DNA: formation of complex DNA.", "content": "A soluble cell-free extract derived from stage 6 Xenopus laevis oocytes is described. From supercoiled simian virus 40 DNA the extract produces nicked circles (having a single-strand scission), linear molecules of full unit size, shorter length fragments, and various forms of complex DNA.", "contents": "Effect of Xenopus laevis oocyte extract on supercoiled simian virus 40 DNA: formation of complex DNA. A soluble cell-free extract derived from stage 6 Xenopus laevis oocytes is described. From supercoiled simian virus 40 DNA the extract produces nicked circles (having a single-strand scission), linear molecules of full unit size, shorter length fragments, and various forms of complex DNA."} {"id": "PMID:174112", "title": "Association of cell surface receptors for melanotropin with the Golgi region in mouse melanoma cells.", "content": "Binding of beta-melanotropin (betal-melanocyte stimulating hormone) to mouse melanoma cells occurs in a region on the cell surface overlying the Golgi complex. This association was demonstrated by labeling cells with fluorescein isothiocyanate hormone and by locating the Golgi complex with a histochemical test for thiamine pyrophosphatase activity. The biologically active fluorescent hormone appears on the surface and later in vesicles in the malanized cells, as judged by fluorescence microscopy. It is conceivable that internalization of the hormone is instrumental in the process of hormonally induced melanization. Because initial and late events of hormonally induced pigmentation are related to the Golgi complex, it is likely that instructions that follow the attachment of melanotropin to receptors are carried out in a compartmentalized manner.", "contents": "Association of cell surface receptors for melanotropin with the Golgi region in mouse melanoma cells. Binding of beta-melanotropin (betal-melanocyte stimulating hormone) to mouse melanoma cells occurs in a region on the cell surface overlying the Golgi complex. This association was demonstrated by labeling cells with fluorescein isothiocyanate hormone and by locating the Golgi complex with a histochemical test for thiamine pyrophosphatase activity. The biologically active fluorescent hormone appears on the surface and later in vesicles in the malanized cells, as judged by fluorescence microscopy. It is conceivable that internalization of the hormone is instrumental in the process of hormonally induced melanization. Because initial and late events of hormonally induced pigmentation are related to the Golgi complex, it is likely that instructions that follow the attachment of melanotropin to receptors are carried out in a compartmentalized manner."} {"id": "PMID:174113", "title": "Regulation by steroid hormones of phosphorylation of specific protein common to several target organs.", "content": "The effect of in vivo administration of steroid hormones on the endogenous phosphorylation of individual proteins in cell sap from several target tissues has been studied using the technique of discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hormones studied (and their respective target organs) were: 17 beta-estradiol [1,3,5(10)-estratriene-3, 17beta-diol] (uterus); testosterone (17 beta-hydroxy-4-androsten-3-one) (ventral prostate and seminal vesicle)' cortisol (11beta, 17alpha, 21-trihydroxy-4-pregnene-3,20-dione) (liver); aldosterone (the 18.11-hemiacetal of 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al) (toad bladder). In each of the five target organs studied, pretreatment with the appropriate hormone reduced the amount of 32P incorporated from [gamma-32P]ATP into an apparently common protein band present in the cytosol fraction. The endogenous phosphorylation and dephosphorylation of this protein was also regulated by cAMP. This protein, designated SCARP (steroid and cyclic adenosine 3':5' monophosphate regulated phosphoprotein), was estimated to have an apparent molecular phoprotein), was estimated to have an apparent molecular weight of 54,000 in the gel electrophoresis system used. The effect of the steroid hormones in decreasing the phosphorylation of SCARP was specific for their respective target tissues. The effect of 17beta-estradiol and of testosterone on SCARP could be observed as early as two hours after a single dose of the steroid. A protein synthesis inhibitor, cycloheximide, abolished the effect of the steroid hormones, but not that of cAMP, on the endogenous phosphorylation of SCARP. The results suggest that steroid hormones regulate either the amount of SCARP or its ability to become phosphorylated. This regulation of a single species of protein by several types of steroid hormones in different target organs raises the possibility that this common biochemical action may be a component of the mechanism by which these steroids achieve some of their biological effects.", "contents": "Regulation by steroid hormones of phosphorylation of specific protein common to several target organs. The effect of in vivo administration of steroid hormones on the endogenous phosphorylation of individual proteins in cell sap from several target tissues has been studied using the technique of discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hormones studied (and their respective target organs) were: 17 beta-estradiol [1,3,5(10)-estratriene-3, 17beta-diol] (uterus); testosterone (17 beta-hydroxy-4-androsten-3-one) (ventral prostate and seminal vesicle)' cortisol (11beta, 17alpha, 21-trihydroxy-4-pregnene-3,20-dione) (liver); aldosterone (the 18.11-hemiacetal of 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al) (toad bladder). In each of the five target organs studied, pretreatment with the appropriate hormone reduced the amount of 32P incorporated from [gamma-32P]ATP into an apparently common protein band present in the cytosol fraction. The endogenous phosphorylation and dephosphorylation of this protein was also regulated by cAMP. This protein, designated SCARP (steroid and cyclic adenosine 3':5' monophosphate regulated phosphoprotein), was estimated to have an apparent molecular phoprotein), was estimated to have an apparent molecular weight of 54,000 in the gel electrophoresis system used. The effect of the steroid hormones in decreasing the phosphorylation of SCARP was specific for their respective target tissues. The effect of 17beta-estradiol and of testosterone on SCARP could be observed as early as two hours after a single dose of the steroid. A protein synthesis inhibitor, cycloheximide, abolished the effect of the steroid hormones, but not that of cAMP, on the endogenous phosphorylation of SCARP. The results suggest that steroid hormones regulate either the amount of SCARP or its ability to become phosphorylated. This regulation of a single species of protein by several types of steroid hormones in different target organs raises the possibility that this common biochemical action may be a component of the mechanism by which these steroids achieve some of their biological effects."} {"id": "PMID:174114", "title": "Inhibition of tumor cell proliferation by dimerized ribonuclease.", "content": "A cross-linked dimer of pancreatic ribonuclease A (ribonucleate 3'-pyrimidino-olitonucleotidohydrolase, EC 3.1.4.22), at a 10 mg/liter concentration, blocks proliferation of tumor cells. The protein retains this ability after inactivation by iodoacetate. The cytostatic effect of ribonuclease preparations on various cell lines correlates well with their rate of uptake: for example, monomeric ribonuclease A is much less effective and is taken up into the cells 10 t0 15 times more slowly. Cell fractionation studies on hepatoma cells indicate accumulation of the dimer in the lysosomal system. Ribonuclease dimer induces a labilization of the lysosomes when added to cell homogenates, raising the possibility that its antitumoral effect may be mediated by endocytosis and lysosomes.", "contents": "Inhibition of tumor cell proliferation by dimerized ribonuclease. A cross-linked dimer of pancreatic ribonuclease A (ribonucleate 3'-pyrimidino-olitonucleotidohydrolase, EC 3.1.4.22), at a 10 mg/liter concentration, blocks proliferation of tumor cells. The protein retains this ability after inactivation by iodoacetate. The cytostatic effect of ribonuclease preparations on various cell lines correlates well with their rate of uptake: for example, monomeric ribonuclease A is much less effective and is taken up into the cells 10 t0 15 times more slowly. Cell fractionation studies on hepatoma cells indicate accumulation of the dimer in the lysosomal system. Ribonuclease dimer induces a labilization of the lysosomes when added to cell homogenates, raising the possibility that its antitumoral effect may be mediated by endocytosis and lysosomes."} {"id": "PMID:174115", "title": "New gene locus modifying susceptibility to certain B-tropic murine leukemia viruses.", "content": "A new gene, SRV, the dominant allele of which occurs in mice of strain C57BL, independently modifies the slope (\"hitness\") and level of sensitivity of the titration curves obtained when one subclass of B-tropic murine leukemia viruses is propagated on mouse embryo cells of nonpermissive Fv-1 genotypes. Replication of another subclass of B-tropic viruses is not modified with respect to hitness, and that of N-tropic viruses is not affected.", "contents": "New gene locus modifying susceptibility to certain B-tropic murine leukemia viruses. A new gene, SRV, the dominant allele of which occurs in mice of strain C57BL, independently modifies the slope (\"hitness\") and level of sensitivity of the titration curves obtained when one subclass of B-tropic murine leukemia viruses is propagated on mouse embryo cells of nonpermissive Fv-1 genotypes. Replication of another subclass of B-tropic viruses is not modified with respect to hitness, and that of N-tropic viruses is not affected."} {"id": "PMID:174116", "title": "Suppression of murine type-C RNA virogenes by type-specific oncornavirus vaccines: prospects for prevention of cancer.", "content": "Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology.", "contents": "Suppression of murine type-C RNA virogenes by type-specific oncornavirus vaccines: prospects for prevention of cancer. Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology."} {"id": "PMID:174117", "title": "Activation of an endogenous mouse type C virus by ultraviolet-irradiated herpes simplex virus types 1 and 2.", "content": "Infection of BALB/c mouse cells with UV-irradiated herpes simplex virus (HSV) types 1 and 2 resulted in activation of a xenotropic type C virus detected by infectious center formation in permissive rat cells. The levels of type C virus activated by HSV were related to the UV dose and the multiplicity of infection used. The ability of HSV to activate type C virus was eliminated by heat-inactivation and by neutralization with specific antiserum against HSV, but was not affected by purification or treatment with DNase and RNase. Maximum levels of type C virus in the cells and medium were observed within 1 day after HSV infection, and the levels returned to control cell values within 3-4 days. The possible significance of these findings with respect to the putative oncogenic potential of HSV is discussed.", "contents": "Activation of an endogenous mouse type C virus by ultraviolet-irradiated herpes simplex virus types 1 and 2. Infection of BALB/c mouse cells with UV-irradiated herpes simplex virus (HSV) types 1 and 2 resulted in activation of a xenotropic type C virus detected by infectious center formation in permissive rat cells. The levels of type C virus activated by HSV were related to the UV dose and the multiplicity of infection used. The ability of HSV to activate type C virus was eliminated by heat-inactivation and by neutralization with specific antiserum against HSV, but was not affected by purification or treatment with DNase and RNase. Maximum levels of type C virus in the cells and medium were observed within 1 day after HSV infection, and the levels returned to control cell values within 3-4 days. The possible significance of these findings with respect to the putative oncogenic potential of HSV is discussed."} {"id": "PMID:174129", "title": "The pathogenesis of simian varicella virus in cynomolgus monkeys.", "content": "The MLM herpesvirus is infectious for cynomolgus monkeys. The disease in this species, possibly modulated by preinoculation antibody resembles human varicella. Virus has been recovered from blood during the early incubation period, and from liver, lymph nodes, kidney, bladder and urine during the eruptive period of infection. The major target organs were skin and liver; specific pathological changes developed in both. Appropriate antibody responses, including those to Herpesvirus varicellae followed infections mounted by parenteral inoculation of cynomolgus monkeys.", "contents": "The pathogenesis of simian varicella virus in cynomolgus monkeys. The MLM herpesvirus is infectious for cynomolgus monkeys. The disease in this species, possibly modulated by preinoculation antibody resembles human varicella. Virus has been recovered from blood during the early incubation period, and from liver, lymph nodes, kidney, bladder and urine during the eruptive period of infection. The major target organs were skin and liver; specific pathological changes developed in both. Appropriate antibody responses, including those to Herpesvirus varicellae followed infections mounted by parenteral inoculation of cynomolgus monkeys."} {"id": "PMID:174131", "title": "Effects of hyperlipoproteinemic serum and exogenous proline concentration on collagen synthesis by isolated rabbit aortas.", "content": "Collagen synthesis was measured in segments of normal rabbit aorta, incubated in vitro, by monitoring the formation of peptidyl-14C-hydroxyproline from [U-14C]-L-proline added to the incubation medium. The effect of hyperlipoproteinemic rabbit serum on the rate of collagen synthesis was compared with the effect of normal rabbit serum. No differences in the rates of synthesis were detected between the two batches of serum, despite a 60-fold difference in serum cholesterol concentration. Increases in free proline concentration in the incubation medium resulted in changes in proline flux between medium and tissue pools of free proline, but medium proline concentration had no effect on the rate of collagen synthesis.", "contents": "Effects of hyperlipoproteinemic serum and exogenous proline concentration on collagen synthesis by isolated rabbit aortas. Collagen synthesis was measured in segments of normal rabbit aorta, incubated in vitro, by monitoring the formation of peptidyl-14C-hydroxyproline from [U-14C]-L-proline added to the incubation medium. The effect of hyperlipoproteinemic rabbit serum on the rate of collagen synthesis was compared with the effect of normal rabbit serum. No differences in the rates of synthesis were detected between the two batches of serum, despite a 60-fold difference in serum cholesterol concentration. Increases in free proline concentration in the incubation medium resulted in changes in proline flux between medium and tissue pools of free proline, but medium proline concentration had no effect on the rate of collagen synthesis."} {"id": "PMID:174133", "title": "The inhibition of angiotensin converting enzyme in chronic renal hypertension by a synthetic peptide.", "content": "Renal hypertension was produced in 14 Sprague-Dawley rats by ligating both poles of one kidney followed in one week by unilateral nephrectomy. Biweekly subcutaneous injections of SQ 20858 reduced the blood pressure in the chronic renal hypertensive animals. Upon discontinuing the injections the blood pressure rose to pretreatment levels. No angiotensin II activity was seen in seven of the renal group treated with SQ indicating a complete block in serum converting enzyme activity. Likewise, serum with only angiotensin I activity when added to normal serum containing converting enzyme, continued to show angiotensin I activity. It is concluded that SQ 20858 is effective in lowering blood pressure in chronic renal hypertensive rats presumably by partially inhibiting converting enzyme.", "contents": "The inhibition of angiotensin converting enzyme in chronic renal hypertension by a synthetic peptide. Renal hypertension was produced in 14 Sprague-Dawley rats by ligating both poles of one kidney followed in one week by unilateral nephrectomy. Biweekly subcutaneous injections of SQ 20858 reduced the blood pressure in the chronic renal hypertensive animals. Upon discontinuing the injections the blood pressure rose to pretreatment levels. No angiotensin II activity was seen in seven of the renal group treated with SQ indicating a complete block in serum converting enzyme activity. Likewise, serum with only angiotensin I activity when added to normal serum containing converting enzyme, continued to show angiotensin I activity. It is concluded that SQ 20858 is effective in lowering blood pressure in chronic renal hypertensive rats presumably by partially inhibiting converting enzyme."} {"id": "PMID:174134", "title": "Assay of kinins by their effects on canine femoral blood flow.", "content": "In pentobarbital anesthetized dogs, close arterial injections of bradykinin and kallidin elicit a dose related increase in femoral blood flow. Treatment with the kininase inhibitor BPP9alpha augments the femoral blood flow responses to bradykinin and kallidin by five and threefold respectively. The sensitivity of the preparation permits the detection of 0.5-1 ng of either bradykinin or kallidin in untreated dogs and as little as 0.1 ng of kinin peptides in animals receiving BPP9alpha. This sensitivity and the steepness of the dose response curves make this procedure suitable for the assay of kinins.", "contents": "Assay of kinins by their effects on canine femoral blood flow. In pentobarbital anesthetized dogs, close arterial injections of bradykinin and kallidin elicit a dose related increase in femoral blood flow. Treatment with the kininase inhibitor BPP9alpha augments the femoral blood flow responses to bradykinin and kallidin by five and threefold respectively. The sensitivity of the preparation permits the detection of 0.5-1 ng of either bradykinin or kallidin in untreated dogs and as little as 0.1 ng of kinin peptides in animals receiving BPP9alpha. This sensitivity and the steepness of the dose response curves make this procedure suitable for the assay of kinins."} {"id": "PMID:174136", "title": "Phosphoprotein phosphatase activity in the thyroid.", "content": "Phosphoprotein phosphatase activity in the calf thyroid was found in various subcellular fractions. The relative amount in each fraction varied according to the substrate used: The 500g fraction had the highest specific activity when protamine was used, while the 5000g fraction was highest when histone was used. Triton X-100 tended to increase activity in all the particulate fractions, the greatest change being found in the 105,000g pellet. DEAE chromatography of the 105,000 g supernatant resolved at least three peaks of phosphoprotein phosphatase activity.", "contents": "Phosphoprotein phosphatase activity in the thyroid. Phosphoprotein phosphatase activity in the calf thyroid was found in various subcellular fractions. The relative amount in each fraction varied according to the substrate used: The 500g fraction had the highest specific activity when protamine was used, while the 5000g fraction was highest when histone was used. Triton X-100 tended to increase activity in all the particulate fractions, the greatest change being found in the 105,000g pellet. DEAE chromatography of the 105,000 g supernatant resolved at least three peaks of phosphoprotein phosphatase activity."} {"id": "PMID:174137", "title": "Enhancement and interference in chickens inoculated with Marek's disease herpesvirus and oncornaviruses.", "content": "Enhancement of mortality rates and symptomatology was observed in isolator-held LSI-SPF chickens concurrently inoculated with MDHV and avian oncornaviruses (RAV-1, RAV-2, RAV-7, RAV-50, or REV). Interference with MD antigen production also was demonstrated in extracts of the feather follicle epithelium from chickens inoculated with both MDHV and RAV-1.", "contents": "Enhancement and interference in chickens inoculated with Marek's disease herpesvirus and oncornaviruses. Enhancement of mortality rates and symptomatology was observed in isolator-held LSI-SPF chickens concurrently inoculated with MDHV and avian oncornaviruses (RAV-1, RAV-2, RAV-7, RAV-50, or REV). Interference with MD antigen production also was demonstrated in extracts of the feather follicle epithelium from chickens inoculated with both MDHV and RAV-1."} {"id": "PMID:174138", "title": "Feedback inhibition by 6-methylthioinosine 3',5'-cyclic monophosphate in tumor cells resistant to the nucleoside.", "content": "The 3',5'-cyclic phosphate derivative (cMTIMP) of methylthioinosine (MTI) was shown to produce feedback inhibition of the de novo purine pathway in an Ehrlich ascites tumor subline resistant to MTI because of lack of adenosine kinase activity for the nucleoside analog.", "contents": "Feedback inhibition by 6-methylthioinosine 3',5'-cyclic monophosphate in tumor cells resistant to the nucleoside. The 3',5'-cyclic phosphate derivative (cMTIMP) of methylthioinosine (MTI) was shown to produce feedback inhibition of the de novo purine pathway in an Ehrlich ascites tumor subline resistant to MTI because of lack of adenosine kinase activity for the nucleoside analog."} {"id": "PMID:174139", "title": "Characteristics common to choleretic increments of bile induced by theophylline, glucagon and SQ-20009 in the dog.", "content": "Theophylline, glucagon, and SQ-20009 induce a choleresis in the dog characterized by a proportionate increase in erythritol clearance and bile flow, no increase in bile salt excretion, and by an isosmotic solution of similar electrolyte composition. The increment in bile appears to originate at the canaliculus in response to increased cyclic-AMP.", "contents": "Characteristics common to choleretic increments of bile induced by theophylline, glucagon and SQ-20009 in the dog. Theophylline, glucagon, and SQ-20009 induce a choleresis in the dog characterized by a proportionate increase in erythritol clearance and bile flow, no increase in bile salt excretion, and by an isosmotic solution of similar electrolyte composition. The increment in bile appears to originate at the canaliculus in response to increased cyclic-AMP."} {"id": "PMID:174140", "title": "The effect of octadecenoic acid on the growth of japanese encephalitis virus in Novikoff hepatoma cells.", "content": "The growth characteristics of Japanese encephalitis virus cultivated in Novikoff hepatoma cells grown in shaker culture can be differentially altered by the presence of 6-cis or cis-9-octadecenoic acid in Swim's 67-G medium. The addition of 125 mug of the 6-isomer per ml medium reduced the number of infectious particles produced, whereas the same amount of the 9-isomer enhanced virus production. The virus was found to be more stable in cell-free spent medium than in fresh medium. The presence of 125 mug 6-18:1 per ml in fresh medium resulted in a rapid loss of virus infectivity.", "contents": "The effect of octadecenoic acid on the growth of japanese encephalitis virus in Novikoff hepatoma cells. The growth characteristics of Japanese encephalitis virus cultivated in Novikoff hepatoma cells grown in shaker culture can be differentially altered by the presence of 6-cis or cis-9-octadecenoic acid in Swim's 67-G medium. The addition of 125 mug of the 6-isomer per ml medium reduced the number of infectious particles produced, whereas the same amount of the 9-isomer enhanced virus production. The virus was found to be more stable in cell-free spent medium than in fresh medium. The presence of 125 mug 6-18:1 per ml in fresh medium resulted in a rapid loss of virus infectivity."} {"id": "PMID:174141", "title": "Lethal synergy between sarcoma-180/TG cells and vesicular stomatitis virus in mice.", "content": "An interaction between sarcoma-180/TG cells and vesicular stomatitis virus in adult mice resulted in the rapid onset of extensive mortality. This interaction, termed lethal synergy, occurred only at early stages of ascites induction in animals with no prior virus contact. A significant sparing effect conferred by the serotonin antagonist dibenamine was reversed by the administration of serotonin. The cause of death was not determined, but a mechanism involving hypersensitivity is indicated.", "contents": "Lethal synergy between sarcoma-180/TG cells and vesicular stomatitis virus in mice. An interaction between sarcoma-180/TG cells and vesicular stomatitis virus in adult mice resulted in the rapid onset of extensive mortality. This interaction, termed lethal synergy, occurred only at early stages of ascites induction in animals with no prior virus contact. A significant sparing effect conferred by the serotonin antagonist dibenamine was reversed by the administration of serotonin. The cause of death was not determined, but a mechanism involving hypersensitivity is indicated."} {"id": "PMID:174142", "title": "Genital infection of female hamsters with herpesvirus hominis type 2 (HVH-2).", "content": "Intravaginal inoculation of female hamsters (40-65 g) with HVH-2 (6 X 105 PFU) results in an infection of 40-67% of the animals. The illness is characterized by vaginitis with discharge, paralysis, and finally death. Washing the vagina with saline 30 min prior to virus inoculation enhances the infection so that 80-100% of the animals eventually die. Virus can be isolated from the vagina within 1-2 days after inoculation. Evidence of infection of the spinal cord is apparent by the third day whereas virus could not be isolated from the brain until Day 5. Attempts to demonstrate virus in whole blood, spleen, kidney, or liver homogenates prepared from infected animals were negative.", "contents": "Genital infection of female hamsters with herpesvirus hominis type 2 (HVH-2). Intravaginal inoculation of female hamsters (40-65 g) with HVH-2 (6 X 105 PFU) results in an infection of 40-67% of the animals. The illness is characterized by vaginitis with discharge, paralysis, and finally death. Washing the vagina with saline 30 min prior to virus inoculation enhances the infection so that 80-100% of the animals eventually die. Virus can be isolated from the vagina within 1-2 days after inoculation. Evidence of infection of the spinal cord is apparent by the third day whereas virus could not be isolated from the brain until Day 5. Attempts to demonstrate virus in whole blood, spleen, kidney, or liver homogenates prepared from infected animals were negative."} {"id": "PMID:174145", "title": "Reticulo-reticular relationship during sleep and waking.", "content": "The mode of interaction between so-called sleep-waking centers during different phases of consciousness was investigated in the cat. Averaged evoked responses were recorded from different centers to electrical stimulation of a center. The results showed that most sleep-waking centers are not simply engaged in the realization of a single phase, but operate during different phases in dynamic relationship with other centers. It was suggested that the mechanism of SS would be more diffusely distributed in the brain stem that presently conceived and that in contrast to the mechanism of PS, that of SS would have more extensive interaction with the mechanisms responsible to other phases.", "contents": "Reticulo-reticular relationship during sleep and waking. The mode of interaction between so-called sleep-waking centers during different phases of consciousness was investigated in the cat. Averaged evoked responses were recorded from different centers to electrical stimulation of a center. The results showed that most sleep-waking centers are not simply engaged in the realization of a single phase, but operate during different phases in dynamic relationship with other centers. It was suggested that the mechanism of SS would be more diffusely distributed in the brain stem that presently conceived and that in contrast to the mechanism of PS, that of SS would have more extensive interaction with the mechanisms responsible to other phases."} {"id": "PMID:174149", "title": "[Possibility of thermography to differentiate pigmental skin tumors (author's transl)].", "content": "Problems and criteria to evaluate thermographic profiles and the differentiation of pigmental skin tumors are discussed.", "contents": "[Possibility of thermography to differentiate pigmental skin tumors (author's transl)]. Problems and criteria to evaluate thermographic profiles and the differentiation of pigmental skin tumors are discussed."} {"id": "PMID:174150", "title": "Oncogenesis and other late effects of cancer treatment in children.", "content": "Review of hospital charts of 168 patients surviving two or more years following the diagnosis of cancer and subsequent-examinations of 40 of these patients yielded these observations: (a) Hospital charts were adequate to ascertain the number of second primary neoplasms. Three malignant and eight benign tumors were found, an incidence of 6.5%. (b) The three patients with second malignant neoplasms did not receive chemotherapy and two of three were treated with radiation. (c) Abnormalities other than second neoplasms, which may have been delayed consequences of treatment, were infrequently noted in hospital records, but were subsequently detected on specific examinations.", "contents": "Oncogenesis and other late effects of cancer treatment in children. Review of hospital charts of 168 patients surviving two or more years following the diagnosis of cancer and subsequent-examinations of 40 of these patients yielded these observations: (a) Hospital charts were adequate to ascertain the number of second primary neoplasms. Three malignant and eight benign tumors were found, an incidence of 6.5%. (b) The three patients with second malignant neoplasms did not receive chemotherapy and two of three were treated with radiation. (c) Abnormalities other than second neoplasms, which may have been delayed consequences of treatment, were infrequently noted in hospital records, but were subsequently detected on specific examinations."} {"id": "PMID:174162", "title": "[The effect of unsaturated fatty acids on the lipoprotein composition of rats].", "content": "Young male rats of the Long-Evans strain were fed 10% lard or corn oil diets for 4 weeks. Analysis of plasma cholesterol showed a decrease of 22%; a decrease of the same order of magnitude as also observed in the lipoproteins, particularly in the VLDL fraction, with the unsaturated diet. Plasma triglycerides were reduced by 50%; their fatty acids were found to contain a higher proportion of linoleate and arachidonate. Cholesterol ester of the HDL fraction contained mostly arachidonate which increased significantly with the substitution of corn oil to lard. Analysis of the lipoproteins indicated a reduction in VLDL and an increase in HDL with the unsaturated diet, whereas LDL remained unchanged.", "contents": "[The effect of unsaturated fatty acids on the lipoprotein composition of rats]. Young male rats of the Long-Evans strain were fed 10% lard or corn oil diets for 4 weeks. Analysis of plasma cholesterol showed a decrease of 22%; a decrease of the same order of magnitude as also observed in the lipoproteins, particularly in the VLDL fraction, with the unsaturated diet. Plasma triglycerides were reduced by 50%; their fatty acids were found to contain a higher proportion of linoleate and arachidonate. Cholesterol ester of the HDL fraction contained mostly arachidonate which increased significantly with the substitution of corn oil to lard. Analysis of the lipoproteins indicated a reduction in VLDL and an increase in HDL with the unsaturated diet, whereas LDL remained unchanged."} {"id": "PMID:174161", "title": "[Mark's disease: V. Experimental behavior of 3 isolates taken place in the country].", "content": "Three experiments were designed to determine the parameters of virus infection, antibodies and mortality with three different MD isolates inoculated in one day old birds from commercial origin. The animals were divided in three inoculated lots (1-2-3) and three control groups (4-1, 4-2, 4-3) and were followed weekly from hatching through 17 weeks. The former were inoculated respectivelly with FOV-6, FCV-8 and FCV-9. Each day old bird received between 50-75 FPU/bird by I.P. route. Samples were taken from circulating blood of five birds by cardiac puncture with an heparinized syringe (20 U/ml), were centrifuged and the white cells inoculated to 5-15 four day old embryos by yolk salk route for virus detection; plasma was assayed by immunodiffusion against MD antigen in order to detect precipitating antibodies, and mortality was recorded after microscopical examination. Infection appeared to persist indefinitelly in the host chicken flock and coexist with (100%) precipiting antibodies, (Fig. 1-2-3). First virus isolation was accomplished after 4 weeks post-inoculation and the 100% porcentage of antibodies, was found only 1-3 weeks after the first peak of viraemia. With the most pathogenic isolate FCV-6 (ig. 1) the antibody response was significantly delayed. Maternal antibodies decreased more rapidly in inoculated than in control birds. Accumulative mortality showed isolate FCV-6 and FCV-8 as pathogenic strains and FCV-9 strain as less pathogenic. Mortality begun 1-3 weeks after the first peak of virus detection in the flock, independently of the pathogenic pattern of the isolate, but frecuencies of death were markedly different.", "contents": "[Mark's disease: V. Experimental behavior of 3 isolates taken place in the country]. Three experiments were designed to determine the parameters of virus infection, antibodies and mortality with three different MD isolates inoculated in one day old birds from commercial origin. The animals were divided in three inoculated lots (1-2-3) and three control groups (4-1, 4-2, 4-3) and were followed weekly from hatching through 17 weeks. The former were inoculated respectivelly with FOV-6, FCV-8 and FCV-9. Each day old bird received between 50-75 FPU/bird by I.P. route. Samples were taken from circulating blood of five birds by cardiac puncture with an heparinized syringe (20 U/ml), were centrifuged and the white cells inoculated to 5-15 four day old embryos by yolk salk route for virus detection; plasma was assayed by immunodiffusion against MD antigen in order to detect precipitating antibodies, and mortality was recorded after microscopical examination. Infection appeared to persist indefinitelly in the host chicken flock and coexist with (100%) precipiting antibodies, (Fig. 1-2-3). First virus isolation was accomplished after 4 weeks post-inoculation and the 100% porcentage of antibodies, was found only 1-3 weeks after the first peak of viraemia. With the most pathogenic isolate FCV-6 (ig. 1) the antibody response was significantly delayed. Maternal antibodies decreased more rapidly in inoculated than in control birds. Accumulative mortality showed isolate FCV-6 and FCV-8 as pathogenic strains and FCV-9 strain as less pathogenic. Mortality begun 1-3 weeks after the first peak of virus detection in the flock, independently of the pathogenic pattern of the isolate, but frecuencies of death were markedly different."} {"id": "PMID:174168", "title": "Nicotinamide adenine dinucleotide degradation in infarcted cardiac muscle.", "content": "Nicotinamide adenine dinucleotides (NAD, NADH2, NADP, and NADPH2) levels decrease in myocardial dog tissue after the ligature of the coronary artery branch. The activity of a glycohydrolytic enzyme acting on NAD and releasing nicotinamide in an equivalent amount was of the same order of magnitude in infarcted tissue, irrespective of the time elapsed after the coronary artery occlusion, as it was in normal tissue. Most of the NAD contained in normal heart muscle was hydrolyzed as soon as the tissue was disrupted in a homogenizer, whereas no hydrolysis occurred when the whole fragment was incubated for 1 hour. The enzymatic activity was found mainly in a membranous fraction seperated at 17,000 x g by differential centrifugation. Acid phosphatase, K+ -activated phosphatase, and NA+-K+-ATPase specific activities were greater in this fraction. It is suggested that the structural disorganization of the heart elicited either in vitro or during the infarction process determines the conditions for a reaction between the enzyme which is localized in the membranes and the NAD which is mainly in the cytosol.", "contents": "Nicotinamide adenine dinucleotide degradation in infarcted cardiac muscle. Nicotinamide adenine dinucleotides (NAD, NADH2, NADP, and NADPH2) levels decrease in myocardial dog tissue after the ligature of the coronary artery branch. The activity of a glycohydrolytic enzyme acting on NAD and releasing nicotinamide in an equivalent amount was of the same order of magnitude in infarcted tissue, irrespective of the time elapsed after the coronary artery occlusion, as it was in normal tissue. Most of the NAD contained in normal heart muscle was hydrolyzed as soon as the tissue was disrupted in a homogenizer, whereas no hydrolysis occurred when the whole fragment was incubated for 1 hour. The enzymatic activity was found mainly in a membranous fraction seperated at 17,000 x g by differential centrifugation. Acid phosphatase, K+ -activated phosphatase, and NA+-K+-ATPase specific activities were greater in this fraction. It is suggested that the structural disorganization of the heart elicited either in vitro or during the infarction process determines the conditions for a reaction between the enzyme which is localized in the membranes and the NAD which is mainly in the cytosol."} {"id": "PMID:174169", "title": "Metabolic and inotropic effects of verapamil in perfused rat heart.", "content": "The effect of verapamil on myocardial contractility, heart adenosine 3', 5'-monophosphate (cyclic AMP) and cardiac phosphorylase a activity was studied in isolated perfused rat hearts. In a concentration of 0.025 mug/ml, verapamil decreased force of contraction 50% and caused a significant fall in heart cyclic AMP within 4 to 5 min after perfusion with the drug was begun. When perfusion of the heart with medium containing verapamil was continued for 60 min, contractile force gradually returned to control. at the end of 60 min of perfusion with verapamil, the myocardial concentration of cyclic AMP was not different from that measured in hearts perfused with contro medium for a similar time period. Isoproterenol, given at the point of maximal contractile depression induced by verapamil, restored normal force of contraction and raised cardiac cyclic AMP to the same level as that observed when the catecholamine was given to untreated hearts; When methoxamine was administered to hearts depressed by verapamil, contractility returned to normal, but cyclic AMP content remained below control values.", "contents": "Metabolic and inotropic effects of verapamil in perfused rat heart. The effect of verapamil on myocardial contractility, heart adenosine 3', 5'-monophosphate (cyclic AMP) and cardiac phosphorylase a activity was studied in isolated perfused rat hearts. In a concentration of 0.025 mug/ml, verapamil decreased force of contraction 50% and caused a significant fall in heart cyclic AMP within 4 to 5 min after perfusion with the drug was begun. When perfusion of the heart with medium containing verapamil was continued for 60 min, contractile force gradually returned to control. at the end of 60 min of perfusion with verapamil, the myocardial concentration of cyclic AMP was not different from that measured in hearts perfused with contro medium for a similar time period. Isoproterenol, given at the point of maximal contractile depression induced by verapamil, restored normal force of contraction and raised cardiac cyclic AMP to the same level as that observed when the catecholamine was given to untreated hearts; When methoxamine was administered to hearts depressed by verapamil, contractility returned to normal, but cyclic AMP content remained below control values."} {"id": "PMID:174175", "title": "[Comparative study of biological case findings made with 1 and with 2 units of PPD].", "content": "Testings were carried out with one unit of PPD in 2865 children aged between 1 and 6 years in the course of 1972 and with two units of PPD in 2822 children aged between 1 and 6 years in the course of 1973. The aspect of the histograms of the two groups was clearly different, the one corresponding to 2 units, tested children showing a more marked bi-modal aspect due to the higher number of reactions of 10-11 mm in diameter (7,5%). The data resulting from the processing of the histograms, of the infecting density of the environment and of the median diameters of the reactions were not conclusive. Between the children tested with one unit 6 cases were detected (5 of which with active tuberculosis), while between those tested with 2 units 22 cases were found (one of wich with an active form of tuberculosis). Among the children tested with one unit of PPD contamination sources could be detected in 100% of the cases and in those tested with 2 units in 51,2% of the cases. The methodology based on the exclusive examination of hyperallergics to one unit of PPD and of their contacts, as compared with the examination of all positive reactions to 2 units and of their contacts has a resolution ability which is higher for an amount of work roughly 30 times less, but in the detection campaign it may omit sick children and contaminators that have not been known until the investigation. The author suggests for the examination of all positive cases with reactions to 2 units of PPD and of their contacts.", "contents": "[Comparative study of biological case findings made with 1 and with 2 units of PPD]. Testings were carried out with one unit of PPD in 2865 children aged between 1 and 6 years in the course of 1972 and with two units of PPD in 2822 children aged between 1 and 6 years in the course of 1973. The aspect of the histograms of the two groups was clearly different, the one corresponding to 2 units, tested children showing a more marked bi-modal aspect due to the higher number of reactions of 10-11 mm in diameter (7,5%). The data resulting from the processing of the histograms, of the infecting density of the environment and of the median diameters of the reactions were not conclusive. Between the children tested with one unit 6 cases were detected (5 of which with active tuberculosis), while between those tested with 2 units 22 cases were found (one of wich with an active form of tuberculosis). Among the children tested with one unit of PPD contamination sources could be detected in 100% of the cases and in those tested with 2 units in 51,2% of the cases. The methodology based on the exclusive examination of hyperallergics to one unit of PPD and of their contacts, as compared with the examination of all positive reactions to 2 units and of their contacts has a resolution ability which is higher for an amount of work roughly 30 times less, but in the detection campaign it may omit sick children and contaminators that have not been known until the investigation. The author suggests for the examination of all positive cases with reactions to 2 units of PPD and of their contacts."} {"id": "PMID:174176", "title": "[Urogenital tuberculosis in antituberculosis dispensary practice].", "content": "The investigations carried out within the district depending upon the dispensary showed that urogenital tuberculosis incidence is in the second place, after respiratory tuberculosis; in 47% of the cases it was the only manifestation of the disease, in the other cases it was secondary to or accompanied other tuberculous localizations.", "contents": "[Urogenital tuberculosis in antituberculosis dispensary practice]. The investigations carried out within the district depending upon the dispensary showed that urogenital tuberculosis incidence is in the second place, after respiratory tuberculosis; in 47% of the cases it was the only manifestation of the disease, in the other cases it was secondary to or accompanied other tuberculous localizations."} {"id": "PMID:174177", "title": "[Study of adverse reactions in pulmonary tuberculosis patients treated with rifampicin].", "content": "The present study concerns the clinical appraisal of adverse reactions reported in the course of Rifampicin (RMP) treatment, reactions which have given rise to conflicting reports. The lot studied included 243 cases of pulmonary tuberculosis of which 57 were treated according to the 7/7 regime (600 mg RMP), 152 according to the 2/7 regimen (900-1200 mg RMP) and 34 according to the 7/7 followed by the 2/7 regimen. Tolerance to RMP was followed up by a series of adequate tests and close clinical surveillance. Adverse reactions developed in 31.5% to 41.5% of the cases in terms of the treatment scheme. In the intermittent treatment adverse reactions occurred in 17.1% of the cases.", "contents": "[Study of adverse reactions in pulmonary tuberculosis patients treated with rifampicin]. The present study concerns the clinical appraisal of adverse reactions reported in the course of Rifampicin (RMP) treatment, reactions which have given rise to conflicting reports. The lot studied included 243 cases of pulmonary tuberculosis of which 57 were treated according to the 7/7 regime (600 mg RMP), 152 according to the 2/7 regimen (900-1200 mg RMP) and 34 according to the 7/7 followed by the 2/7 regimen. Tolerance to RMP was followed up by a series of adequate tests and close clinical surveillance. Adverse reactions developed in 31.5% to 41.5% of the cases in terms of the treatment scheme. In the intermittent treatment adverse reactions occurred in 17.1% of the cases."} {"id": "PMID:174178", "title": "[Comparative immediate results after the use of several lyophilized BCG vaccines].", "content": "A number of 1928 children were vaccinated intradermally with 12 series of BCG vaccine produced by the Cantacuzino Institute and 2 experimental vaccines, prepared in the same laboratory by the same current technique, i.e. a Romanian strain and a French strain, lot 1173 P2. With the experimental vaccines 2 doses were used, with the other vaccines a single standard dose of 0.10 mg. Appraisal of tuberculin sensitivity 8-10 weeks after vaccination showed differences in tuberculin duration, varying between 13.23 mm and 16.27 mm in diameter with the selected vaccines (using 2 units PPD) and were much smaller (8.6 mm -- 12.28 mm) with the operational series of vaccines.", "contents": "[Comparative immediate results after the use of several lyophilized BCG vaccines]. A number of 1928 children were vaccinated intradermally with 12 series of BCG vaccine produced by the Cantacuzino Institute and 2 experimental vaccines, prepared in the same laboratory by the same current technique, i.e. a Romanian strain and a French strain, lot 1173 P2. With the experimental vaccines 2 doses were used, with the other vaccines a single standard dose of 0.10 mg. Appraisal of tuberculin sensitivity 8-10 weeks after vaccination showed differences in tuberculin duration, varying between 13.23 mm and 16.27 mm in diameter with the selected vaccines (using 2 units PPD) and were much smaller (8.6 mm -- 12.28 mm) with the operational series of vaccines."} {"id": "PMID:174173", "title": "[Effects of ACTH on plasma insulin and glucose].", "content": "The authors studied the effects of intramuscular and intravenous administration of ACTH on plasma glucose and insulin in rabbits. They found well marked differences --specially in insulin behavior-- between the effects of ACTH in rabbits and in humans. In rabbits, the investigators observed hyperinsulinism unable to decrease glycemia levels. These data are discussed.", "contents": "[Effects of ACTH on plasma insulin and glucose]. The authors studied the effects of intramuscular and intravenous administration of ACTH on plasma glucose and insulin in rabbits. They found well marked differences --specially in insulin behavior-- between the effects of ACTH in rabbits and in humans. In rabbits, the investigators observed hyperinsulinism unable to decrease glycemia levels. These data are discussed."} {"id": "PMID:174179", "title": "[Abacillary cavitary pulmonary tuberculosis not treated with bacteriostatics].", "content": "A study was carried out on 48 cases of tuberculosis with a clinical and radiologic symptomatology but negative at the repeated bacteriologic examinations. The results suggested that these might be cases of spontaneous recovery since there were no evolutive radiologic signs. Although the lack of contagion may be admitted these cases especially the young children should be isolated and kept under radiologic and bacteriologic surveillance for at least three years.", "contents": "[Abacillary cavitary pulmonary tuberculosis not treated with bacteriostatics]. A study was carried out on 48 cases of tuberculosis with a clinical and radiologic symptomatology but negative at the repeated bacteriologic examinations. The results suggested that these might be cases of spontaneous recovery since there were no evolutive radiologic signs. Although the lack of contagion may be admitted these cases especially the young children should be isolated and kept under radiologic and bacteriologic surveillance for at least three years."} {"id": "PMID:174180", "title": "[Bacterio-epidemiological significance of diabetes mellitus-pulmonary tuberculosis syntropy].", "content": "The author discusses infectivity before and after complex treatment with the classical tuberculostatics in 42 diabetics with chronic pulmonary tuberculosis of the total of 78 subjects followed up for three years, the other 36 subjects being compensated metabolically and pulmonarily. Although the number of negative cases increased fourfold there remained a high proportion of bacilli eliminators, the diabetics becoming negative at a much slower rate.", "contents": "[Bacterio-epidemiological significance of diabetes mellitus-pulmonary tuberculosis syntropy]. The author discusses infectivity before and after complex treatment with the classical tuberculostatics in 42 diabetics with chronic pulmonary tuberculosis of the total of 78 subjects followed up for three years, the other 36 subjects being compensated metabolically and pulmonarily. Although the number of negative cases increased fourfold there remained a high proportion of bacilli eliminators, the diabetics becoming negative at a much slower rate."} {"id": "PMID:174185", "title": "Comparison of behaviour of very low density lipoproteins of type III hyperlipoproteinaemia on electrophoresis on paper and on agarose gel with a note on a late (slow) pre-beta VLDL liproprotein.", "content": "The diagnosis of type III hyperlipoproteinaemia is based on the presence of a very low density lipoprotein (VLDL) that on electrophoresis has beta instead of the usual pre-beta mobility. This definition is based on paper electrophoresis. Lipoproteins of type III sera were studied by simultaneous electrophoresis on paper and on agarose gel. On paper the ultracentrifugally isolated VLDL had beta mobility, but on agarose gel their mobility was slightly more rapid than beta. It is thus important to consider the electrophoretic conditions in the diagnosis of type III. The diagnosis of type III is further complicated by the presence of agarose gel electrophoresis - contrary to paper - of a second, a 'late pre-beta VLDL' lipoprotein (LPbeta) in 20-30 per cent of both normal and hyperlipoproteinaemic sera. Quantitative lipoprotein analysis of 609 consecutive sera showed that when LPbeta was present, both in normo- and hyperlipoproteinaemia, certain significant lipoprotein changes occurred. Thus VLDL had a high cholesterol content and a raised cholesterol to triglyceride ratio. Furthermore, the triglyceride content of low density lipoproteins (LDL) was increased. These lipoprotein abnormalities are also seen in type III hyperlipoproteinaemia. With regard both to chemical composition of VLDL and LDL and to electrophoretic mobility on agarose gel of VLDL, type III hyperlipoproteinaemia and LPbeta are similar. The possibility of a metabolic relation is discussed.", "contents": "Comparison of behaviour of very low density lipoproteins of type III hyperlipoproteinaemia on electrophoresis on paper and on agarose gel with a note on a late (slow) pre-beta VLDL liproprotein. The diagnosis of type III hyperlipoproteinaemia is based on the presence of a very low density lipoprotein (VLDL) that on electrophoresis has beta instead of the usual pre-beta mobility. This definition is based on paper electrophoresis. Lipoproteins of type III sera were studied by simultaneous electrophoresis on paper and on agarose gel. On paper the ultracentrifugally isolated VLDL had beta mobility, but on agarose gel their mobility was slightly more rapid than beta. It is thus important to consider the electrophoretic conditions in the diagnosis of type III. The diagnosis of type III is further complicated by the presence of agarose gel electrophoresis - contrary to paper - of a second, a 'late pre-beta VLDL' lipoprotein (LPbeta) in 20-30 per cent of both normal and hyperlipoproteinaemic sera. Quantitative lipoprotein analysis of 609 consecutive sera showed that when LPbeta was present, both in normo- and hyperlipoproteinaemia, certain significant lipoprotein changes occurred. Thus VLDL had a high cholesterol content and a raised cholesterol to triglyceride ratio. Furthermore, the triglyceride content of low density lipoproteins (LDL) was increased. These lipoprotein abnormalities are also seen in type III hyperlipoproteinaemia. With regard both to chemical composition of VLDL and LDL and to electrophoretic mobility on agarose gel of VLDL, type III hyperlipoproteinaemia and LPbeta are similar. The possibility of a metabolic relation is discussed."} {"id": "PMID:174186", "title": "Lecithin:cholesterol acyl transfer in plasma of normal persons in relation to lipid and lipoprotein concentration.", "content": "Information concerning variation in the lecithin:cholesterol acyl transfer (LCAT) rate in normal persons is scanty. We have therefore analyzed the LCAT rate and the lipid and lipoprotein concentrations in the plasma of healthy normolipidemic persons 20-60 years of age, 40 men and 40 women. 10 per decade and sex. Interindividual variation in molar LCAT rate was 57-130 mumol-u(-1)-h-1 (mean +/- 2 S.D.) with no sex difference. Intraindividual variation of molar LCAT rate studied in 8 women and 9 men was shown to be greater than expected from methodological error and was not explainable by the small changes in plasma lipid concentration during the observation period. In the women the molar LCAT rat was lower during the preovulatory phase of the menstrual cycle than during the postovulatory phase. There was positive correlations between the molar LCAT rate and most of the lipid parameters in plasma. By partial correlation analysis a positive correlation was shown between LCAT rate and triglyceride concentration irrespective of other lipid parameters. Keeping triglyceride concentration constant, there was a positive correlation between molar LCAT rate and total phospholipid, unesterified cholesterol, esterified cholesterol, or low-density lipoprotein (LDL) cholesterol concentration. No correlation was found between high-density lipoprotein (HDL) lipid concentration and LCAT rate. Thus in normal subjects there seems to be a direct relation between very low density lipoprotein and LDL lipid concentration and molar LCAT rate but no relation between HDL lipid concentration and LCAT rate.", "contents": "Lecithin:cholesterol acyl transfer in plasma of normal persons in relation to lipid and lipoprotein concentration. Information concerning variation in the lecithin:cholesterol acyl transfer (LCAT) rate in normal persons is scanty. We have therefore analyzed the LCAT rate and the lipid and lipoprotein concentrations in the plasma of healthy normolipidemic persons 20-60 years of age, 40 men and 40 women. 10 per decade and sex. Interindividual variation in molar LCAT rate was 57-130 mumol-u(-1)-h-1 (mean +/- 2 S.D.) with no sex difference. Intraindividual variation of molar LCAT rate studied in 8 women and 9 men was shown to be greater than expected from methodological error and was not explainable by the small changes in plasma lipid concentration during the observation period. In the women the molar LCAT rat was lower during the preovulatory phase of the menstrual cycle than during the postovulatory phase. There was positive correlations between the molar LCAT rate and most of the lipid parameters in plasma. By partial correlation analysis a positive correlation was shown between LCAT rate and triglyceride concentration irrespective of other lipid parameters. Keeping triglyceride concentration constant, there was a positive correlation between molar LCAT rate and total phospholipid, unesterified cholesterol, esterified cholesterol, or low-density lipoprotein (LDL) cholesterol concentration. No correlation was found between high-density lipoprotein (HDL) lipid concentration and LCAT rate. Thus in normal subjects there seems to be a direct relation between very low density lipoprotein and LDL lipid concentration and molar LCAT rate but no relation between HDL lipid concentration and LCAT rate."} {"id": "PMID:174187", "title": "Substrate specificity of lecithin:cholesterol acyltransferase. Esterification of desmosterol, b-sitosterol, and cholecalciferol in human plasma.", "content": "Desmosterol and beta-sitosterol were esterified when incubated with normal human plasma. The initial rate of demosterol esterification was 1.7 times faster, and that of beta-sitosterol 0.4 times slower, than the esterification rate of cholesterol. These ratios were found to be almost the same when plasma from different normal individuals was tested. Plasma from a patient with familial lecithin:cholesterol acyltransferase deficiency did not esterify any of the sterols. The esterification of desmosterol and beta-sitosterol was considerably slower in normal plasma in which in vitro cholesterol esterification previously had taken place. The different esterification rates could not be explained by a different affinity of the plasma lipoproteins for the sterols tested. Cholecalciferol added to normal plasma did not become esterified.", "contents": "Substrate specificity of lecithin:cholesterol acyltransferase. Esterification of desmosterol, b-sitosterol, and cholecalciferol in human plasma. Desmosterol and beta-sitosterol were esterified when incubated with normal human plasma. The initial rate of demosterol esterification was 1.7 times faster, and that of beta-sitosterol 0.4 times slower, than the esterification rate of cholesterol. These ratios were found to be almost the same when plasma from different normal individuals was tested. Plasma from a patient with familial lecithin:cholesterol acyltransferase deficiency did not esterify any of the sterols. The esterification of desmosterol and beta-sitosterol was considerably slower in normal plasma in which in vitro cholesterol esterification previously had taken place. The different esterification rates could not be explained by a different affinity of the plasma lipoproteins for the sterols tested. Cholecalciferol added to normal plasma did not become esterified."} {"id": "PMID:174188", "title": "Characterization of a cobalamin-binding plasma protein from a patient with hepatoma.", "content": "A cobalamin-binding protein has been purified by affinity chromatography from plasma of a patient with hepatoma and a 10,000-fold increase in the concentration of the plasma cobalamin-binding capacity. The protein behaved as normal transcobalamin I in gel filtration, agar gel electrophoresis, immunoelectrophoresis, precipitation by ammonium sulphate, and cobalamin-binding studies. The protein contained 38 per cent carbohydrate, and the relative molecular mass based on amino acid and carbohydrate analyses was 69,000. The molar absorption coefficient of cyanocobalamin bound to the protein was determined to be 36,000 at 362 nm. On amino acid sequencing, one amino terminal was found, and the first 13 residues were determined as Glu-Ile-Ser/Cys-Glu-Val-Ser/Cys-Glu-Glu-Asx-Tyr-Ile-Arg-Leu/Ile.", "contents": "Characterization of a cobalamin-binding plasma protein from a patient with hepatoma. A cobalamin-binding protein has been purified by affinity chromatography from plasma of a patient with hepatoma and a 10,000-fold increase in the concentration of the plasma cobalamin-binding capacity. The protein behaved as normal transcobalamin I in gel filtration, agar gel electrophoresis, immunoelectrophoresis, precipitation by ammonium sulphate, and cobalamin-binding studies. The protein contained 38 per cent carbohydrate, and the relative molecular mass based on amino acid and carbohydrate analyses was 69,000. The molar absorption coefficient of cyanocobalamin bound to the protein was determined to be 36,000 at 362 nm. On amino acid sequencing, one amino terminal was found, and the first 13 residues were determined as Glu-Ile-Ser/Cys-Glu-Val-Ser/Cys-Glu-Glu-Asx-Tyr-Ile-Arg-Leu/Ile."} {"id": "PMID:174189", "title": "Methodological aspects of protein-binding assays for cyclic AMP in human adipose tissue.", "content": "The specificity of the protein-binding assay for cyclic AMP according to Gilman's method (11) was studied in human adipose tissue. A kit assay obtained from Boehringer-Mannheim was used for the study. Impurities in the solvents used for homogenization and extraction influenced the assay and led to serious overestimation of the actual amount of cAMP. This was corrected for by treating the standard and tissue samples in the same manner. Extracts from human adipose tissue contained material that increased the binding of cAMP to the binding protein and let to underestimation of intracellular cAMP by 60-70 per cent. This was overcome by using a protein kinase inhibitor in the assay. Furthermore, when human adipose tissue was incubated in an albumin-containing medium, intracellular cAMP was underestimated by 30 per cent, since albumin increased the binding of camp to the binding protein.", "contents": "Methodological aspects of protein-binding assays for cyclic AMP in human adipose tissue. The specificity of the protein-binding assay for cyclic AMP according to Gilman's method (11) was studied in human adipose tissue. A kit assay obtained from Boehringer-Mannheim was used for the study. Impurities in the solvents used for homogenization and extraction influenced the assay and led to serious overestimation of the actual amount of cAMP. This was corrected for by treating the standard and tissue samples in the same manner. Extracts from human adipose tissue contained material that increased the binding of cAMP to the binding protein and let to underestimation of intracellular cAMP by 60-70 per cent. This was overcome by using a protein kinase inhibitor in the assay. Furthermore, when human adipose tissue was incubated in an albumin-containing medium, intracellular cAMP was underestimated by 30 per cent, since albumin increased the binding of camp to the binding protein."} {"id": "PMID:174190", "title": "Isotachophoresis: a new technique for determination of tissue metabolite concentrations.", "content": "An electrophoretic technique, isotachophoresis, has been adapted for qualitative and quantitative analysis of metabolites in human muscle tissue. Metabolite concentrations exceeding 0.1 nmol X kg-1 wet muslce could be determined in 5-10 mg muscle biopsy samples generally in good agreement with conventional analytical methods.", "contents": "Isotachophoresis: a new technique for determination of tissue metabolite concentrations. An electrophoretic technique, isotachophoresis, has been adapted for qualitative and quantitative analysis of metabolites in human muscle tissue. Metabolite concentrations exceeding 0.1 nmol X kg-1 wet muslce could be determined in 5-10 mg muscle biopsy samples generally in good agreement with conventional analytical methods."} {"id": "PMID:174191", "title": "Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids.", "content": "Herpes simplex virus (HSV) was recovered from the cerebrospinal fluids (CSF) of 10 patients with acute aseptic meningitis. HSV type 1 was isolated from the CSF of a 6-month-old boy. The other 9 HSV isolates from CSF were from adults in the age-group 15 to 29 years; 7 of these isolates were available for typing and were identified as HSV type 2. In a further 9 patients with acute aseptic meningitis and belonging to the same age-group a HSV infection was suggested by a significant titre rise in complement-fixing antibodies against HSV. The clinical features of the 10 patients with HSV isolation from CSF are presented. The 6-month-old boy with HSV type 1 had an acute benign aseptic meningitis. Seven of the 9 adults with HSV isolation from CSF (type 2 in all isolates available for typing) had an acute uncomplicated aseptic meningitis, one patient (with type 2 isolated) had an acute meningoencephalitis and one (isolate untyped) an acute meningomyelitis.", "contents": "Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids. Herpes simplex virus (HSV) was recovered from the cerebrospinal fluids (CSF) of 10 patients with acute aseptic meningitis. HSV type 1 was isolated from the CSF of a 6-month-old boy. The other 9 HSV isolates from CSF were from adults in the age-group 15 to 29 years; 7 of these isolates were available for typing and were identified as HSV type 2. In a further 9 patients with acute aseptic meningitis and belonging to the same age-group a HSV infection was suggested by a significant titre rise in complement-fixing antibodies against HSV. The clinical features of the 10 patients with HSV isolation from CSF are presented. The 6-month-old boy with HSV type 1 had an acute benign aseptic meningitis. Seven of the 9 adults with HSV isolation from CSF (type 2 in all isolates available for typing) had an acute uncomplicated aseptic meningitis, one patient (with type 2 isolated) had an acute meningoencephalitis and one (isolate untyped) an acute meningomyelitis."} {"id": "PMID:174195", "title": "[Functional aortic systolic murmurs in the elderly].", "content": "The authors report a clinical and phonocardiographic study of functional aortic systolic murmurs in 26 elderly patients, in 19 of which the lesion was confirmed pathologically. Systolic murmurs radiating across the chest in elderly have the same clinical characteristics as aortic stenosis from which they may, however, be distinguished owing to the: absence of a thrill during systole. The brief duration and the proto-meso-systolic position of the murmur with early inscription of maximal oscillations on the phonocardiogram. Conversion of the second aortic sound. Almost constant absence of a diastolic murmur. Normal carotid arteriogram, including normal ejection time after correction and time of half rise. \"Innocent\" systolic murmurs are due to calcification of the aortic valve without stenosis, and/or dilatation of the ascending aorta. There is no systolic pressure gradient between the left ventricle and the aorta during cardiac catheterisation. No lesions were found in the mitral valve suggesting mitral incompetence, therefore, we consider the term mitro-aortic murmur used by Huchard should be dropped; Radiation of the murmur from the apex of the heart up into the neck may be explained by the simultaneous occurrence of anatomical changes due to age and/or hypertension and by the vibratory nature of the murmurs which become propagated above and below their origin, as shown by the intracardiac recordings.", "contents": "[Functional aortic systolic murmurs in the elderly]. The authors report a clinical and phonocardiographic study of functional aortic systolic murmurs in 26 elderly patients, in 19 of which the lesion was confirmed pathologically. Systolic murmurs radiating across the chest in elderly have the same clinical characteristics as aortic stenosis from which they may, however, be distinguished owing to the: absence of a thrill during systole. The brief duration and the proto-meso-systolic position of the murmur with early inscription of maximal oscillations on the phonocardiogram. Conversion of the second aortic sound. Almost constant absence of a diastolic murmur. Normal carotid arteriogram, including normal ejection time after correction and time of half rise. \"Innocent\" systolic murmurs are due to calcification of the aortic valve without stenosis, and/or dilatation of the ascending aorta. There is no systolic pressure gradient between the left ventricle and the aorta during cardiac catheterisation. No lesions were found in the mitral valve suggesting mitral incompetence, therefore, we consider the term mitro-aortic murmur used by Huchard should be dropped; Radiation of the murmur from the apex of the heart up into the neck may be explained by the simultaneous occurrence of anatomical changes due to age and/or hypertension and by the vibratory nature of the murmurs which become propagated above and below their origin, as shown by the intracardiac recordings."} {"id": "PMID:174196", "title": "[Various etiologies of systolic murmurs radiating from the apex of the heart to the neck].", "content": "The authors studied systolic murmurs in 89 cases, 50 of aortic stenosis, 14 cases of obstructive cardiomyopathy and 20 cases of mitral incompetence. This systolic murmur is characterised by its exceptional intensity, its raspy character at the base, becoming softer at the apex and in the axilla, the presence of a thrill and irradiation into the neck in 50 to 75% of cases. The etiological diagnosis was ensured precisely by 1) pharmaco-dynamic tests: amyl nitrite accentuates the systolic ejection murmurs and attenuates murmurs due to mitral regurgitation. 2) careful analysis of diastole: a systolic murmur extending into early diastole, a third sound or an opening snap and a low-pitched diastolic murmur, suggest mitral incompetence. A high-pitched diastolic murmur is in favour of aortic stenosis. 3) the carotid arteriogram and catheterisation show the characteristic abnormalities of the carotid arteriogram found in aortic valve disease and the existence of a trans-aortic or intra-ventricular pressure gradient, when there is an obstruction to left ventricular jection. The F wave of the apex cardiogram or left atrial reflux of the contrast medium during cineangiocardiography, confirm mitral incompetence. The main phono-hemodynamic and phono-anatomical correlations have been emphasized: 1. The intensity of the systolic murmur is directly proportional to the degree of obstructive cardiomyopathy or mitral incompetence, but does not parallel the degree of the sub-valvular apparatus. 3. The maximum intensity of the murmur occurs all the later when the stenosis is tight, whilst it is earlier in severe obstructive cardio-myopathy. 4. The lozange shape of the murmur of mitral incompetence on phono-cardiography is, above all, due to those cases with lesions of the sub-valvular apparatus. Finally, a study of the sound recorded by the Allard-Laurens micromanometer permitted us to determine the mechanism of this irradiating systolic murmur.", "contents": "[Various etiologies of systolic murmurs radiating from the apex of the heart to the neck]. The authors studied systolic murmurs in 89 cases, 50 of aortic stenosis, 14 cases of obstructive cardiomyopathy and 20 cases of mitral incompetence. This systolic murmur is characterised by its exceptional intensity, its raspy character at the base, becoming softer at the apex and in the axilla, the presence of a thrill and irradiation into the neck in 50 to 75% of cases. The etiological diagnosis was ensured precisely by 1) pharmaco-dynamic tests: amyl nitrite accentuates the systolic ejection murmurs and attenuates murmurs due to mitral regurgitation. 2) careful analysis of diastole: a systolic murmur extending into early diastole, a third sound or an opening snap and a low-pitched diastolic murmur, suggest mitral incompetence. A high-pitched diastolic murmur is in favour of aortic stenosis. 3) the carotid arteriogram and catheterisation show the characteristic abnormalities of the carotid arteriogram found in aortic valve disease and the existence of a trans-aortic or intra-ventricular pressure gradient, when there is an obstruction to left ventricular jection. The F wave of the apex cardiogram or left atrial reflux of the contrast medium during cineangiocardiography, confirm mitral incompetence. The main phono-hemodynamic and phono-anatomical correlations have been emphasized: 1. The intensity of the systolic murmur is directly proportional to the degree of obstructive cardiomyopathy or mitral incompetence, but does not parallel the degree of the sub-valvular apparatus. 3. The maximum intensity of the murmur occurs all the later when the stenosis is tight, whilst it is earlier in severe obstructive cardio-myopathy. 4. The lozange shape of the murmur of mitral incompetence on phono-cardiography is, above all, due to those cases with lesions of the sub-valvular apparatus. Finally, a study of the sound recorded by the Allard-Laurens micromanometer permitted us to determine the mechanism of this irradiating systolic murmur."} {"id": "PMID:174197", "title": "[Supravalvular ring type aortic stenosis with hypoplasia of the ascending aorta and stenosis of the origin of the innominate artery. Surgical correction].", "content": "The authors report the case of a 19 year old woman with supravalvar aortic stenosis and hypoplasia of the ascending aorta with stenosis at the origin of the innominate artery. This was a sporadic form, without mental deficiency nor facial dysmorphia. No similar case was found in the family. The patient had three attacks of bacterial endocarditis over a period of 3 years and became cured without any cardiac sequelae. In view of the onset of left ventricular failure and sequelae. In view of the onset of left ventricular failure and syncope, operation was decided. A lozange-shaped patch was placed on the aorta from the narrowed supravalvar part to the origin of the innominate artery and prolonged on the latter vessel after relief of the stenosis. This gave an excellent result.", "contents": "[Supravalvular ring type aortic stenosis with hypoplasia of the ascending aorta and stenosis of the origin of the innominate artery. Surgical correction]. The authors report the case of a 19 year old woman with supravalvar aortic stenosis and hypoplasia of the ascending aorta with stenosis at the origin of the innominate artery. This was a sporadic form, without mental deficiency nor facial dysmorphia. No similar case was found in the family. The patient had three attacks of bacterial endocarditis over a period of 3 years and became cured without any cardiac sequelae. In view of the onset of left ventricular failure and sequelae. In view of the onset of left ventricular failure and syncope, operation was decided. A lozange-shaped patch was placed on the aorta from the narrowed supravalvar part to the origin of the innominate artery and prolonged on the latter vessel after relief of the stenosis. This gave an excellent result."} {"id": "PMID:174198", "title": "[Istope examinations in coronary intensive care units].", "content": "Radio-isotopes may be of use in investigation of patients with heart disease on an intensive care unit. These investigations are not traumatic. The radio-isotopes are innocuous and reliable, the examinations may be easily repeated and are therefore of great interest in diagnosis and prognosis of cardiovascular disease.", "contents": "[Istope examinations in coronary intensive care units]. Radio-isotopes may be of use in investigation of patients with heart disease on an intensive care unit. These investigations are not traumatic. The radio-isotopes are innocuous and reliable, the examinations may be easily repeated and are therefore of great interest in diagnosis and prognosis of cardiovascular disease."} {"id": "PMID:174199", "title": "[Indications for permanent electrosystolic pacing in arrhythmia revealed or aggravated by treatment].", "content": "The authors report 25 cases of patients, average age 67 years with severe coronary or valvular heart disease, with conduction disorders. The conduction disorder occurred alone in 8 cases and was associated with a disorder of excitability in 17 cases. It was either obvious, as in 14 cases, or latent, as in 11 cases, and precipitated by various forms of treatment, the disadvantage of which was the negative dromotrope effect. This treatment was prescribed for permanent resting angina (amiodarone and prenylamine), heart failure (digitoxin) or excitability disorder (beta-blockaders or procainamide). 11 patients had one or several fainting attacks. Permanent electro-systolic pacing with stimulation on demand, is necessary in all patients to palliate the consequences of treatment. In 11 cases out of 25, prior temporary pacing permitted the authors to assess the efficacy of treatment. The high post-operative mortality (40%) is not due to the apparatus but depends on the severity of the coronary heart disease or heart failure in these patients, In 60% of cases, the result of stimulation was excellent and was maintained permanently.", "contents": "[Indications for permanent electrosystolic pacing in arrhythmia revealed or aggravated by treatment]. The authors report 25 cases of patients, average age 67 years with severe coronary or valvular heart disease, with conduction disorders. The conduction disorder occurred alone in 8 cases and was associated with a disorder of excitability in 17 cases. It was either obvious, as in 14 cases, or latent, as in 11 cases, and precipitated by various forms of treatment, the disadvantage of which was the negative dromotrope effect. This treatment was prescribed for permanent resting angina (amiodarone and prenylamine), heart failure (digitoxin) or excitability disorder (beta-blockaders or procainamide). 11 patients had one or several fainting attacks. Permanent electro-systolic pacing with stimulation on demand, is necessary in all patients to palliate the consequences of treatment. In 11 cases out of 25, prior temporary pacing permitted the authors to assess the efficacy of treatment. The high post-operative mortality (40%) is not due to the apparatus but depends on the severity of the coronary heart disease or heart failure in these patients, In 60% of cases, the result of stimulation was excellent and was maintained permanently."} {"id": "PMID:174200", "title": "[Reye's syndrome: pathological study of 2 cases].", "content": "The authors report two personal cases of Reye's syndrome, one of which was studied by electron microscopy, and comment on the pathological characteristics of this disease. The hepatic lesions are most important and resemble fatty degeneration rather than simple steatosis. This notion is confirmed by data obtained by electron microscopy which revealed marked abnormalities of the cellular organites, in particular, mitochondria. The nervous involvement included mainly, oedema of the nerve sheath. These facts emphasize the importance of metabolic disturbances in the physiopathology of the disease.", "contents": "[Reye's syndrome: pathological study of 2 cases]. The authors report two personal cases of Reye's syndrome, one of which was studied by electron microscopy, and comment on the pathological characteristics of this disease. The hepatic lesions are most important and resemble fatty degeneration rather than simple steatosis. This notion is confirmed by data obtained by electron microscopy which revealed marked abnormalities of the cellular organites, in particular, mitochondria. The nervous involvement included mainly, oedema of the nerve sheath. These facts emphasize the importance of metabolic disturbances in the physiopathology of the disease."} {"id": "PMID:174201", "title": "[Destructive lesions of the middle and lower part of the cervical spine during rheumatoid arthritis. Study of the neurological complications. A case with quadriplegia].", "content": "Lesions of the middle and lower part of the cervical spine during rheumatoid arthritis are less frequent than those of the cervico-occipital joint. They concern the discs on the one hand, the posterior inter-apophyseal joints, on the other hand. The authors report a case of rheumatic spondylodiscitis of C5-C6 with dislocation, complicated by quadriplegia, and review other published cases of rheumatoid lesions of the middle and lower cervical spine with neurological complications. The mechanisms of these lesions and their complications are then discussed.", "contents": "[Destructive lesions of the middle and lower part of the cervical spine during rheumatoid arthritis. Study of the neurological complications. A case with quadriplegia]. Lesions of the middle and lower part of the cervical spine during rheumatoid arthritis are less frequent than those of the cervico-occipital joint. They concern the discs on the one hand, the posterior inter-apophyseal joints, on the other hand. The authors report a case of rheumatic spondylodiscitis of C5-C6 with dislocation, complicated by quadriplegia, and review other published cases of rheumatoid lesions of the middle and lower cervical spine with neurological complications. The mechanisms of these lesions and their complications are then discussed."} {"id": "PMID:174202", "title": "[Different pathogenic power of the original BCG strain of the Pasteur Institute and of an isoniazid resistant strain. Histopathological study and significance of local abscesses after inoculation of guinea pig].", "content": "The inoculation into guinea pigs of 10 mg of BCG, obtained either from the Pasteur Institute original strain, or from a mutant isoniazid resistant strain, B1 catalase positive, caused in 40.4% of cases, the onset of abscesses at the point of injection. The frequency and course of these abscesses appear quite different with the two strains, 92.8% with the classical strain, persisting in more than half of the cases after one year, and 23.5% with the INH-resistant strains which regressed within 6 months. Histologically, the structure of the recent abscesses, with a large histiocytic wall often rich in bacteria, and a very cellular necrotic content, appears different from that of old abscesses with a thin wall and a heterogeneous content, calcification with reaction to foreign bodies, and presence of granules due to the persistance of bacteria. The INH-resistant strain is thus in the guinea pig, less aggressive and more rapidly eliminated than the classical Pasteur strain. The course and morphology of abscesses in guinea pigs are very similar to certain old lesions of human tuberculosis and involve, in all strains, phenomena of cell immunity both general and local.", "contents": "[Different pathogenic power of the original BCG strain of the Pasteur Institute and of an isoniazid resistant strain. Histopathological study and significance of local abscesses after inoculation of guinea pig]. The inoculation into guinea pigs of 10 mg of BCG, obtained either from the Pasteur Institute original strain, or from a mutant isoniazid resistant strain, B1 catalase positive, caused in 40.4% of cases, the onset of abscesses at the point of injection. The frequency and course of these abscesses appear quite different with the two strains, 92.8% with the classical strain, persisting in more than half of the cases after one year, and 23.5% with the INH-resistant strains which regressed within 6 months. Histologically, the structure of the recent abscesses, with a large histiocytic wall often rich in bacteria, and a very cellular necrotic content, appears different from that of old abscesses with a thin wall and a heterogeneous content, calcification with reaction to foreign bodies, and presence of granules due to the persistance of bacteria. The INH-resistant strain is thus in the guinea pig, less aggressive and more rapidly eliminated than the classical Pasteur strain. The course and morphology of abscesses in guinea pigs are very similar to certain old lesions of human tuberculosis and involve, in all strains, phenomena of cell immunity both general and local."} {"id": "PMID:174203", "title": "[Camptodactyly. Apropos of 25 cases].", "content": "In a group of 120 mental patients, the authors found obvious camptodactyly in 65 patients (46%), especially in psychopaths, neurotics and related conditions. Clinical, psychological, radiological and laboratory investigations were carried out in 25 of these cases. The disease was accompanied by disorders of glucose metabolism, endocrine abnormalities, EEG and bone abnormalities together with arthrosis. The mental disorder, causing an inability to return to work, attracted our attention to the series of abnormalities found in these subjects investigated.", "contents": "[Camptodactyly. Apropos of 25 cases]. In a group of 120 mental patients, the authors found obvious camptodactyly in 65 patients (46%), especially in psychopaths, neurotics and related conditions. Clinical, psychological, radiological and laboratory investigations were carried out in 25 of these cases. The disease was accompanied by disorders of glucose metabolism, endocrine abnormalities, EEG and bone abnormalities together with arthrosis. The mental disorder, causing an inability to return to work, attracted our attention to the series of abnormalities found in these subjects investigated."} {"id": "PMID:174205", "title": "[Prenatal diagnosis of genetic diseases. Results of 57 early amniocenteses].", "content": "The authors report the results of anmiocenteses carried out early in 57 cases, in order to detect hereditary disorders in high risk pregnancies. They emphasize the necessity of prior genetic consultation and obstetric examination. Among the 57 cases, 53 had the examination carried out in order to seek a chromosome anomaly. The techniques of removal and culture are described. One pregnancy was interrupted, the foetus had a chromosome abnormality. The psychological aspect and the necessity of close cooperation between gynecologists and geneticians are discussed.", "contents": "[Prenatal diagnosis of genetic diseases. Results of 57 early amniocenteses]. The authors report the results of anmiocenteses carried out early in 57 cases, in order to detect hereditary disorders in high risk pregnancies. They emphasize the necessity of prior genetic consultation and obstetric examination. Among the 57 cases, 53 had the examination carried out in order to seek a chromosome anomaly. The techniques of removal and culture are described. One pregnancy was interrupted, the foetus had a chromosome abnormality. The psychological aspect and the necessity of close cooperation between gynecologists and geneticians are discussed."} {"id": "PMID:174218", "title": "[Cystadenocarcinoma of the pancreas. Apropos of 2 cases].", "content": "The authors report two cases of cystadenocarcinoma of the pancreas and review the clinical, radiological and angiographic findings. The pathological study may be first disappointing, especially on frozen sections in the operating theater. The diagnosis depends essentially on the finding of an epithelial border which is difficult to demonstrate for it is often interrupted on one part of the circumference. Malignancy is suggested by the characteristics of the cells and the structural disorganisation. Total removal is necessary to avoid relapses, provided one removes neighbouring organs and all invaded lymph nodes. Cystadenomas and cystadeno-carcinomas are very rare tumours. The passage from one to the other seems inevitable. The necessity for surgery is thus absolute. However, if the malignant tumour is irremovable, an anastomosis between the cyst and the digestive tract may temporarily relieve the patient, especially as the course is sometimes rather slow.", "contents": "[Cystadenocarcinoma of the pancreas. Apropos of 2 cases]. The authors report two cases of cystadenocarcinoma of the pancreas and review the clinical, radiological and angiographic findings. The pathological study may be first disappointing, especially on frozen sections in the operating theater. The diagnosis depends essentially on the finding of an epithelial border which is difficult to demonstrate for it is often interrupted on one part of the circumference. Malignancy is suggested by the characteristics of the cells and the structural disorganisation. Total removal is necessary to avoid relapses, provided one removes neighbouring organs and all invaded lymph nodes. Cystadenomas and cystadeno-carcinomas are very rare tumours. The passage from one to the other seems inevitable. The necessity for surgery is thus absolute. However, if the malignant tumour is irremovable, an anastomosis between the cyst and the digestive tract may temporarily relieve the patient, especially as the course is sometimes rather slow."} {"id": "PMID:174219", "title": "[Chronic tubulo-interstitial nephropathy and tapetal-retinal degeneration. Senior's syndrome?].", "content": "Following Contreras and Espinoza in 1960, Senior and Loken, in 1961, described a new familial entity in which were associated renal and eye involvement in addition to Alport and Lowe's syndromes. About 30 cases of this syndrome have been reported until now. We report here a new case discovered with very advanced renal failure. No metabolic or enzymatic abnormality of the lysosomes was discovered. The family history and an investigation of the parents and six other siblings, did not reveal any similar case. Frequency of the morbid association, interstitial nephritis and retinal degeneration, is definitely underestimated. It raises numerous problems concerning the hereditary causes and the metabolic nature of both conditions, together with its place in classification of tubulo-interstitial nephritis described under the term of nephronophtisis. In practice, recognition of this association should permit early detection of the various components and assessment of the prognosis and family risk.", "contents": "[Chronic tubulo-interstitial nephropathy and tapetal-retinal degeneration. Senior's syndrome?]. Following Contreras and Espinoza in 1960, Senior and Loken, in 1961, described a new familial entity in which were associated renal and eye involvement in addition to Alport and Lowe's syndromes. About 30 cases of this syndrome have been reported until now. We report here a new case discovered with very advanced renal failure. No metabolic or enzymatic abnormality of the lysosomes was discovered. The family history and an investigation of the parents and six other siblings, did not reveal any similar case. Frequency of the morbid association, interstitial nephritis and retinal degeneration, is definitely underestimated. It raises numerous problems concerning the hereditary causes and the metabolic nature of both conditions, together with its place in classification of tubulo-interstitial nephritis described under the term of nephronophtisis. In practice, recognition of this association should permit early detection of the various components and assessment of the prognosis and family risk."} {"id": "PMID:174220", "title": "[Complications of lymphography. A propos of 5 cases].", "content": "Complications noted following lymphography have been published by several authors. The authors report here a series of 5 cases occurring in patients with mediastinal and lung cancer. They report the various clinical manifestations resembling fat embolism, the free interval and general signs, pulmonary, neurological, hematological and dermatological symptoms associated with inconstant laboratory abnormalities which permit one to suggest a complex pathogenesis: --Immuno-allergic (early shock due to circulating antibodies). --Mechanical and vascular: incomplete removal of low viscosity lipiodol by the pulmonary macrophage system permits liberation of micro-vascular emboli. --By abnormality of blood coagulation and the onset of a syndrome of widespread intravascular coagulation. Better recognition of the pathogenesis associated with the development of new therapeutic principles, should permit better prevention and control of these complications.", "contents": "[Complications of lymphography. A propos of 5 cases]. Complications noted following lymphography have been published by several authors. The authors report here a series of 5 cases occurring in patients with mediastinal and lung cancer. They report the various clinical manifestations resembling fat embolism, the free interval and general signs, pulmonary, neurological, hematological and dermatological symptoms associated with inconstant laboratory abnormalities which permit one to suggest a complex pathogenesis: --Immuno-allergic (early shock due to circulating antibodies). --Mechanical and vascular: incomplete removal of low viscosity lipiodol by the pulmonary macrophage system permits liberation of micro-vascular emboli. --By abnormality of blood coagulation and the onset of a syndrome of widespread intravascular coagulation. Better recognition of the pathogenesis associated with the development of new therapeutic principles, should permit better prevention and control of these complications."} {"id": "PMID:174221", "title": "[Association of multiple basal cell carcinomas of the face and spinocerebellar degeneration. Study of 4 familial cases including an anatomo-clinical description].", "content": "The authors report 4 cases of the morbid familial association revealing itself late in life (average age 37.7 years) including multiple basal cell carcinomas of the face and neurological and psychiatric symptoms, the most complete examples of which were severe, including mixed cerebello-spinal ataxia, involvement of the anterior horns of the spinal cord, a pyramidal syndrome and extra-pyramidal syndrome, abolition of the osteo-tendinous reflexes, dementia, paralysis of certain cranial nerves. These are associated constantly with increased glucose concentration in the cerebro-spinal fluid and dilatation of the cerebral ventricles. The course is unusual. The skin signs always occur first. There is a definite parallel between the severity of the skin involvement and that of the central nervous system. A neuropathological study of one case (case 2) showed lesions of degenerative type resembling spino-cerebellar degeneration of Menzel type with supramedullary diffusion to the locus niger, locus coeruleus, cranial nerves and thalamus. From these clinical and pathological findings, the authors noted an original pathological and clinical entity and consider certain diagnostic and pathological problems. The precise relationship between the skin and nervous lesions is unknown, but may be due to abiotrophic processes. Concerning the classification, this disease should not be included among the phacomatoses for there is no biastema tendency, and should be included among the more general group of neuro-cutaneous dystrophies or genoneurodermatoses.", "contents": "[Association of multiple basal cell carcinomas of the face and spinocerebellar degeneration. Study of 4 familial cases including an anatomo-clinical description]. The authors report 4 cases of the morbid familial association revealing itself late in life (average age 37.7 years) including multiple basal cell carcinomas of the face and neurological and psychiatric symptoms, the most complete examples of which were severe, including mixed cerebello-spinal ataxia, involvement of the anterior horns of the spinal cord, a pyramidal syndrome and extra-pyramidal syndrome, abolition of the osteo-tendinous reflexes, dementia, paralysis of certain cranial nerves. These are associated constantly with increased glucose concentration in the cerebro-spinal fluid and dilatation of the cerebral ventricles. The course is unusual. The skin signs always occur first. There is a definite parallel between the severity of the skin involvement and that of the central nervous system. A neuropathological study of one case (case 2) showed lesions of degenerative type resembling spino-cerebellar degeneration of Menzel type with supramedullary diffusion to the locus niger, locus coeruleus, cranial nerves and thalamus. From these clinical and pathological findings, the authors noted an original pathological and clinical entity and consider certain diagnostic and pathological problems. The precise relationship between the skin and nervous lesions is unknown, but may be due to abiotrophic processes. Concerning the classification, this disease should not be included among the phacomatoses for there is no biastema tendency, and should be included among the more general group of neuro-cutaneous dystrophies or genoneurodermatoses."} {"id": "PMID:174222", "title": "[4 cases of osteomalacia during anticonvulsant or sedative treatment].", "content": "The authors report osteomalacia in 3 cases of epilepsy and one case of coronary heart disease treated with phenobarbitone, either alone or associated with other anticonvulsants. There were clinical signs in all cases and typical radiological signs in 3 cases, a characteristic laboratory syndrome in 4 cases. In the 3 cases where it was estimated, serum levels of parathormone were high. Finally, in 3 cases where it was measured, daily urinary excretion of glucaric D acid was increased. The bony histological signs studied in 3 cases, were similar to those in deficiency osteomalacia. A study of Ca45 metabolism in one case, showed the characteristic changes found in osteomalacia. Finally, a study of the metabolism of tritiated vitamin D, or tritiated 25 OH CC, carried out in 3 cases, gave 3 different patterns; only one of them was characteristic of enzyme induction under the dependency of anticonvulsant. Started in 2 cases, treatment with 125 OH2CC, brought about a rapid fall in blood PTH levels which then rose again before falling progressively in one case, under treatment with 25 OH CC. The bony histological signs of hyperparathyroidism then regressed whilst serum PTH levels remained high. Phosphorous and calcium balance improved in only one case. Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient.", "contents": "[4 cases of osteomalacia during anticonvulsant or sedative treatment]. The authors report osteomalacia in 3 cases of epilepsy and one case of coronary heart disease treated with phenobarbitone, either alone or associated with other anticonvulsants. There were clinical signs in all cases and typical radiological signs in 3 cases, a characteristic laboratory syndrome in 4 cases. In the 3 cases where it was estimated, serum levels of parathormone were high. Finally, in 3 cases where it was measured, daily urinary excretion of glucaric D acid was increased. The bony histological signs studied in 3 cases, were similar to those in deficiency osteomalacia. A study of Ca45 metabolism in one case, showed the characteristic changes found in osteomalacia. Finally, a study of the metabolism of tritiated vitamin D, or tritiated 25 OH CC, carried out in 3 cases, gave 3 different patterns; only one of them was characteristic of enzyme induction under the dependency of anticonvulsant. Started in 2 cases, treatment with 125 OH2CC, brought about a rapid fall in blood PTH levels which then rose again before falling progressively in one case, under treatment with 25 OH CC. The bony histological signs of hyperparathyroidism then regressed whilst serum PTH levels remained high. Phosphorous and calcium balance improved in only one case. Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient."} {"id": "PMID:174226", "title": "Ultrasonic and radionuclide scanning in pancreatic disease.", "content": "Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies.", "contents": "Ultrasonic and radionuclide scanning in pancreatic disease. Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies."} {"id": "PMID:174227", "title": "Bone trauma and related benign disease: assessment by bone scanning.", "content": "The radionuclide investigation of skeletal trauma in the past was confined generally to scintimetry and an occasional bone scan. The development of improved radiopharmaceuticals, including 99mTc-labeled compounds with their enhanced sensitivity, and the refinement of imaging devices offering superior resolution and speed have allowed a more detailed assessment of conditions resulting from trauma. Practical approaches to the diagnosis of subtle bone injury resulting in stress fracture, the differentiation between delayed healing and nonunion, and early recognition of avascular necrosis and osteomyelitis are now available. The changing pattern of radionuclide uptake in bone following damage by radiation and other abnormalities as a consequence of trauma also can be easily studied.", "contents": "Bone trauma and related benign disease: assessment by bone scanning. The radionuclide investigation of skeletal trauma in the past was confined generally to scintimetry and an occasional bone scan. The development of improved radiopharmaceuticals, including 99mTc-labeled compounds with their enhanced sensitivity, and the refinement of imaging devices offering superior resolution and speed have allowed a more detailed assessment of conditions resulting from trauma. Practical approaches to the diagnosis of subtle bone injury resulting in stress fracture, the differentiation between delayed healing and nonunion, and early recognition of avascular necrosis and osteomyelitis are now available. The changing pattern of radionuclide uptake in bone following damage by radiation and other abnormalities as a consequence of trauma also can be easily studied."} {"id": "PMID:174228", "title": "Bone scanning: radionuclidic reaction mechanisms.", "content": "One of the major successes of nuclear medicine in recent years has been the clinical utility of the 99mTc-labeled bone-imaging agents. This article is concerned with the evidence available for the mechanisms by which these and other such radiopharmaceuticals localize at sites in the skeleton.", "contents": "Bone scanning: radionuclidic reaction mechanisms. One of the major successes of nuclear medicine in recent years has been the clinical utility of the 99mTc-labeled bone-imaging agents. This article is concerned with the evidence available for the mechanisms by which these and other such radiopharmaceuticals localize at sites in the skeleton."} {"id": "PMID:174229", "title": "Observations on the mechanism of 99mTc-labeled phosphate complex uptake in metabolic bone disease.", "content": "This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.", "contents": "Observations on the mechanism of 99mTc-labeled phosphate complex uptake in metabolic bone disease. This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction."} {"id": "PMID:174232", "title": "Idiopathic neurotrophic feet in blacks.", "content": "Black patients with idiopathic neurotrophic feet are described and analysed. Evidence is presented to show that the essential pathological lesion is a peripheral neuropathy caused by an excessive consumption of alcohol and a poor diet. It is characterised clinically by a peripheral neuropathy, perforating septic ulcers over pressure points, resorption, and clawing of toes, bilateral foot involvement, usually good foot pulses, and an offensive odour.", "contents": "Idiopathic neurotrophic feet in blacks. Black patients with idiopathic neurotrophic feet are described and analysed. Evidence is presented to show that the essential pathological lesion is a peripheral neuropathy caused by an excessive consumption of alcohol and a poor diet. It is characterised clinically by a peripheral neuropathy, perforating septic ulcers over pressure points, resorption, and clawing of toes, bilateral foot involvement, usually good foot pulses, and an offensive odour."} {"id": "PMID:174233", "title": "Effect of natural oestrogens on blood pressure and weight in postmenopausal women.", "content": "An investigation of the effect of conjugated oestorgens (USP) on the blood pressure and weight gain of postmenopausal women was undertaken. Fifty-one unselected women were treated for one year with cyclically administered conjugated oestrogen. Both the mean systolic and diastolic blood pressures of those in the group increased, but only the diastolic was significantly elevated. Individual evaluation revealed that this was largely owing to an idiosyncrasy among certain women. Age is probably a predisposing factor, for hypertension occurred more frequently among the older women. The significance of the change in blood pressure is commented upon, and the recommendation that postmenopausal women on oestrogen replacement therapy should have their blood pressure measured every 6 months is made. Weight gain is not affected by long-term treatment with conjugated oestrogens.", "contents": "Effect of natural oestrogens on blood pressure and weight in postmenopausal women. An investigation of the effect of conjugated oestorgens (USP) on the blood pressure and weight gain of postmenopausal women was undertaken. Fifty-one unselected women were treated for one year with cyclically administered conjugated oestrogen. Both the mean systolic and diastolic blood pressures of those in the group increased, but only the diastolic was significantly elevated. Individual evaluation revealed that this was largely owing to an idiosyncrasy among certain women. Age is probably a predisposing factor, for hypertension occurred more frequently among the older women. The significance of the change in blood pressure is commented upon, and the recommendation that postmenopausal women on oestrogen replacement therapy should have their blood pressure measured every 6 months is made. Weight gain is not affected by long-term treatment with conjugated oestrogens."} {"id": "PMID:174234", "title": "Liver cell carcinoma during the prime of life.", "content": "During a 23 year period at Memorial Hospital, the diagnosis of liver cell carcinoma was made in 42 patients who were 11 to 40 years old. Ninety per cent were Caucasian, mostly born in the United states. No occupational hazard was detected. Serum hepatitis antigen was demonstrated in only one patient. Alpha fetoprotein was found in the serum of 55 per cent of nine patients tested. Eight-three per cent were Rh positive, 43 per cent were ABO groups, A or O, respectively. Twenty-three per cent of 13 patients with sufficient material for study had an associated cirrhosis. Of these, active hepatitis with cirrhosis was present in one patient; postnecrotic cirrhosis was present in another. Approximately 7 per cent had a history of previous liver disease. One patient had infectious mononucleosis, and nearly 13 per cent gave a family history of cancer. Weight loss or pain in the right upper abdominal quadrant was present in 65 per cent, and hepatomegaly was found in 88 per cent. Only one patient presented with hemoperitoneum simulating an acute condition within abdomen. The liver profile examinations characteristically revealed an elevation in serum alkaline phosphatase, 5 nucleotidase, and Bromsulphalein retention with normal bilirubin level. The most common finding, upon roentgenographic examination, was an elevated right hemidiaphragm. Selective celiac and superior mesenteric angiography and 99mTc sulfur colloid liver scans were both done in 13 patients. There was a 75 per cent accuracy rate in localization of the tumor. At laparotomy, the tumor was found to be confined to one lobe in seven patients and involved both lobes in ten. Twenty-seven patients were thought to have multicentric tumors and 15 unicentric lesions. Only ten were found to be candidates for hepatic lobectomy. Five and ten years survival rates were 20 per cent; the operative mortality rate was 40 per cent. Twenty per cent died within a year, ten per cent, one patient, is alive with disease at 28 months and another is free of disease at 31-months. Paraneoplastic syndromes were erythrocytosis in two patients, terminal stage of hypoglycemia in one patient, and hypocholesterolemia with associated excess beta globulin in one patient.", "contents": "Liver cell carcinoma during the prime of life. During a 23 year period at Memorial Hospital, the diagnosis of liver cell carcinoma was made in 42 patients who were 11 to 40 years old. Ninety per cent were Caucasian, mostly born in the United states. No occupational hazard was detected. Serum hepatitis antigen was demonstrated in only one patient. Alpha fetoprotein was found in the serum of 55 per cent of nine patients tested. Eight-three per cent were Rh positive, 43 per cent were ABO groups, A or O, respectively. Twenty-three per cent of 13 patients with sufficient material for study had an associated cirrhosis. Of these, active hepatitis with cirrhosis was present in one patient; postnecrotic cirrhosis was present in another. Approximately 7 per cent had a history of previous liver disease. One patient had infectious mononucleosis, and nearly 13 per cent gave a family history of cancer. Weight loss or pain in the right upper abdominal quadrant was present in 65 per cent, and hepatomegaly was found in 88 per cent. Only one patient presented with hemoperitoneum simulating an acute condition within abdomen. The liver profile examinations characteristically revealed an elevation in serum alkaline phosphatase, 5 nucleotidase, and Bromsulphalein retention with normal bilirubin level. The most common finding, upon roentgenographic examination, was an elevated right hemidiaphragm. Selective celiac and superior mesenteric angiography and 99mTc sulfur colloid liver scans were both done in 13 patients. There was a 75 per cent accuracy rate in localization of the tumor. At laparotomy, the tumor was found to be confined to one lobe in seven patients and involved both lobes in ten. Twenty-seven patients were thought to have multicentric tumors and 15 unicentric lesions. Only ten were found to be candidates for hepatic lobectomy. Five and ten years survival rates were 20 per cent; the operative mortality rate was 40 per cent. Twenty per cent died within a year, ten per cent, one patient, is alive with disease at 28 months and another is free of disease at 31-months. Paraneoplastic syndromes were erythrocytosis in two patients, terminal stage of hypoglycemia in one patient, and hypocholesterolemia with associated excess beta globulin in one patient."} {"id": "PMID:174235", "title": "Ruptured abdominal aneurysms presenting with unilateral peripheral neuropathy.", "content": "Neurologic deficits uncommonly occur following successful aortic surgery for aneurysm. Two cases are presented in which peripheral neuropathy precipitated the diagnosis of ruptured aneurysm. Both patients had large retroperitoneal hematomas at operation, and the neuropathy was due presumably to compression of the femoral and obturator nerves. Neither patient has shown significant improvement in function in the affected muscles after operation. This represents an important diagnostic sign with leaking or ruptured abdominal aortic aneurysm.", "contents": "Ruptured abdominal aneurysms presenting with unilateral peripheral neuropathy. Neurologic deficits uncommonly occur following successful aortic surgery for aneurysm. Two cases are presented in which peripheral neuropathy precipitated the diagnosis of ruptured aneurysm. Both patients had large retroperitoneal hematomas at operation, and the neuropathy was due presumably to compression of the femoral and obturator nerves. Neither patient has shown significant improvement in function in the affected muscles after operation. This represents an important diagnostic sign with leaking or ruptured abdominal aortic aneurysm."} {"id": "PMID:174237", "title": "Culture of arterial endothelial cells: characterization and growth of bovine aortic cells.", "content": "Arterial endothelial cells were obtained from bovine aortae by mild treatment with collagenase and medium perfusion. These cells were cultured in RPMI-1640 medium containing 15mM Hepes buffer and 35% fetal calf serum at pH 7.35. Essentially all (90-95%) the effluent cells were viable and 80% of these cells attached to the substratum within 1 hour. Small patches of attached cells coalesced to form confluent monolayers in 3-5 days. Confluent monolayers of endothelial cells consisted of a homogeneous population of tightly packed, polygonal cells. Selected cultures were serially subcultured (trypsin-EDTA) for 12-14 months (30-35 passages) without any apparent change in morphology or loss of growth characteristics. Primary and three-month old (15 passages) cultures had population doubling times of 32-34 hours and 29-31 hours, respectively. These cells (primary and subcultures) did not require a minimum cell number to become established in culture. Bovine endothelial cells (primary, first, fifth and thirteenth passages) were characterized ultrastructurally by the presence of Weibel-Palade bodies, pinocytotic vesicles and microfilaments and immunologically by the presence of thrombosthenin-like contractile proteins and Factor VIII antigen. The intercellular junctions of post-confluenct cultures stained specifically with silver nitrate. From these data, we concluded that identifiable endothelial cells could be obtained from bovine aortae and cultured and maintained for prolonged periods of time.", "contents": "Culture of arterial endothelial cells: characterization and growth of bovine aortic cells. Arterial endothelial cells were obtained from bovine aortae by mild treatment with collagenase and medium perfusion. These cells were cultured in RPMI-1640 medium containing 15mM Hepes buffer and 35% fetal calf serum at pH 7.35. Essentially all (90-95%) the effluent cells were viable and 80% of these cells attached to the substratum within 1 hour. Small patches of attached cells coalesced to form confluent monolayers in 3-5 days. Confluent monolayers of endothelial cells consisted of a homogeneous population of tightly packed, polygonal cells. Selected cultures were serially subcultured (trypsin-EDTA) for 12-14 months (30-35 passages) without any apparent change in morphology or loss of growth characteristics. Primary and three-month old (15 passages) cultures had population doubling times of 32-34 hours and 29-31 hours, respectively. These cells (primary and subcultures) did not require a minimum cell number to become established in culture. Bovine endothelial cells (primary, first, fifth and thirteenth passages) were characterized ultrastructurally by the presence of Weibel-Palade bodies, pinocytotic vesicles and microfilaments and immunologically by the presence of thrombosthenin-like contractile proteins and Factor VIII antigen. The intercellular junctions of post-confluenct cultures stained specifically with silver nitrate. From these data, we concluded that identifiable endothelial cells could be obtained from bovine aortae and cultured and maintained for prolonged periods of time."} {"id": "PMID:174240", "title": "The compound eye in the opaque-eye phenotype of Drosophilia melanogaster.", "content": "The compound eye of the opaque-eye mutant of Drosophila melanogaster was investigated by means of electron microscopy to determine the morphological and physical properties of ommatidial elements. These elements in the mutant were found to differ from those of the wild-type flies in the following ways: (1) The cuticular lens was thinner than that of the control and lacked the typical lamellar construction. (2) The Semper cells were irregular in shape and contained many membranous inclusions similar to those found in degenerating cells; also their nuclei contained virus-like particles. (3) The primary pigment cells contained an abundance of drosopterin-containing granules which were lacking in those of wild-type flies. (4) The superior and inferior central photoreceptor cells were misplaced and their rhabdomeres evidenced some degeneration. (5) The secondary pigment cells had only one type of pigment granules instead of the three types found in the control. These morphological changes in ommatidial elements induced physical abnormalities such as the apparent opaqueness of the eye, the lack of a pseudopupil, the probable disability of the photoreceptor cells to respond to light and the inability of the dioptric system to produce utilizable geometric images.", "contents": "The compound eye in the opaque-eye phenotype of Drosophilia melanogaster. The compound eye of the opaque-eye mutant of Drosophila melanogaster was investigated by means of electron microscopy to determine the morphological and physical properties of ommatidial elements. These elements in the mutant were found to differ from those of the wild-type flies in the following ways: (1) The cuticular lens was thinner than that of the control and lacked the typical lamellar construction. (2) The Semper cells were irregular in shape and contained many membranous inclusions similar to those found in degenerating cells; also their nuclei contained virus-like particles. (3) The primary pigment cells contained an abundance of drosopterin-containing granules which were lacking in those of wild-type flies. (4) The superior and inferior central photoreceptor cells were misplaced and their rhabdomeres evidenced some degeneration. (5) The secondary pigment cells had only one type of pigment granules instead of the three types found in the control. These morphological changes in ommatidial elements induced physical abnormalities such as the apparent opaqueness of the eye, the lack of a pseudopupil, the probable disability of the photoreceptor cells to respond to light and the inability of the dioptric system to produce utilizable geometric images."} {"id": "PMID:174241", "title": "Effect of partial thyroidectomy, propylthiouracil or thyroxine on estrogen-induced intranuclear inclusions in mammotrophs of the Mongolian gerbil.", "content": "Partial thyroidectomy caused a significant increase in the number of intranuclear inclusions per field (2-83 +/- 0-10 inclusions as compared with 0-15 +/- 0-03 inclusions for sham-controls). The inclusions occurred exclusively within mammotrophs. Thyrotrophs were stimulated: an increased cell size, numerous secretory granules, an enlarged Golgi apparatus and hypertrophic rough endoplasmic reticulum. Propylthiouracil caused similar ultrastructural changes although sighificantly fewer inclusions were observed (0-64 +/- 0-06 inclusions). Suppression of thyroid function with thyroxine produced no change in the number of inclusions (0-17 +/- 0-03 inclusions) although when combined with estrogen there were significantly fewer inclusions (1-62 +/- 0-07) when compared to estrogen alone (2-69 +/- 0-09). Intranuclear inclusions appear to be a unique reaction of mammotrophs to cellular hyperfunction in the Mongolian gerbil.", "contents": "Effect of partial thyroidectomy, propylthiouracil or thyroxine on estrogen-induced intranuclear inclusions in mammotrophs of the Mongolian gerbil. Partial thyroidectomy caused a significant increase in the number of intranuclear inclusions per field (2-83 +/- 0-10 inclusions as compared with 0-15 +/- 0-03 inclusions for sham-controls). The inclusions occurred exclusively within mammotrophs. Thyrotrophs were stimulated: an increased cell size, numerous secretory granules, an enlarged Golgi apparatus and hypertrophic rough endoplasmic reticulum. Propylthiouracil caused similar ultrastructural changes although sighificantly fewer inclusions were observed (0-64 +/- 0-06 inclusions). Suppression of thyroid function with thyroxine produced no change in the number of inclusions (0-17 +/- 0-03 inclusions) although when combined with estrogen there were significantly fewer inclusions (1-62 +/- 0-07) when compared to estrogen alone (2-69 +/- 0-09). Intranuclear inclusions appear to be a unique reaction of mammotrophs to cellular hyperfunction in the Mongolian gerbil."} {"id": "PMID:174242", "title": "Intranuclear inclusions in mammotrophs of the Mongolian gerbil: effect of low doses of estradiol benzoate and a study of females before weaning.", "content": "The effect of dose of estrogen on induction of intranuclear inclusions was studied in mammotrophs of the Mongolian gerbil. The number of inclusions per high power field increased significantly with 0-5 and 1-0 mug/day of estradiol benzoate but not with the 0-05 mug dose. A form of inclusion was seen in young female gerbils before weaning which suggests that inclusions arise from the cytoplasm. Intranuclear inclusions develop soon after weaning of gerbils (0-06 +/- 0-01 vs. 0-19 +/- 0-03 for young mature females).", "contents": "Intranuclear inclusions in mammotrophs of the Mongolian gerbil: effect of low doses of estradiol benzoate and a study of females before weaning. The effect of dose of estrogen on induction of intranuclear inclusions was studied in mammotrophs of the Mongolian gerbil. The number of inclusions per high power field increased significantly with 0-5 and 1-0 mug/day of estradiol benzoate but not with the 0-05 mug dose. A form of inclusion was seen in young female gerbils before weaning which suggests that inclusions arise from the cytoplasm. Intranuclear inclusions develop soon after weaning of gerbils (0-06 +/- 0-01 vs. 0-19 +/- 0-03 for young mature females)."} {"id": "PMID:174244", "title": "Experimental study of dibutyryl cyclic AMP; its metabolic effects observed in anesthetized human subjects.", "content": "Metabolic effects of N6,O2-dibutyryl adenosine 3',5'-monophosphate (DBcAMP) were studied in 10 anesthetized patients who were divided at random into two groups each consisting of 5 patients. DBcAMP dissolved in 200 ml of physiological saline was administered intravenously at a rate of 10 mg/min for 20 min in one group and 20 mg/min for 20 min in the other group. DBcAMP infusion at either rate increased levels of blood glucose, immunoreactive plasma insulin, blood pyruvate and blood redox-potential while it reduced levels of glycerol, non-esterified fatty acid and inorganic phosphate. These findings suggest that 200 and 400 mg of DBcAMP stimulates glycogenolysis and glycolysis but inhibits lipolysis in man.", "contents": "Experimental study of dibutyryl cyclic AMP; its metabolic effects observed in anesthetized human subjects. Metabolic effects of N6,O2-dibutyryl adenosine 3',5'-monophosphate (DBcAMP) were studied in 10 anesthetized patients who were divided at random into two groups each consisting of 5 patients. DBcAMP dissolved in 200 ml of physiological saline was administered intravenously at a rate of 10 mg/min for 20 min in one group and 20 mg/min for 20 min in the other group. DBcAMP infusion at either rate increased levels of blood glucose, immunoreactive plasma insulin, blood pyruvate and blood redox-potential while it reduced levels of glycerol, non-esterified fatty acid and inorganic phosphate. These findings suggest that 200 and 400 mg of DBcAMP stimulates glycogenolysis and glycolysis but inhibits lipolysis in man."} {"id": "PMID:174245", "title": "Primary cytomegalovirus infection and liver involvement in early infancy.", "content": "Virus isolation and determination of serum transaminase activity in 237 patients under one year of age were undertaken to clarify the etiologic significance of primary infection with cytomegalovirus (CMV) in infancy. The rates of virus recovery from infants with liver involvement were 37% (29/78) and 42% (28/66), as determined by serum glutamic oxaloacetic (S-GOT) and serum glutamic pyruvic (S-GPT) transaminase values. In contrast, CMV was recovered from 14% (18/127) and 13% (18/141) of infants with normal S-GOT and S-GPT values. The differences in the rates of virus recovery between both groups were more pronounced in infants under three months of age, that is, 5 to 7 times higher rates in infants with liver involvement. Correlation between complement-fixing antibody and liver involvement, however, was not significant, probably because of the influence by maternal antibody. Majority of infants infected with CMV are postulated to involve liver during immediate months after onset of virus excretion.", "contents": "Primary cytomegalovirus infection and liver involvement in early infancy. Virus isolation and determination of serum transaminase activity in 237 patients under one year of age were undertaken to clarify the etiologic significance of primary infection with cytomegalovirus (CMV) in infancy. The rates of virus recovery from infants with liver involvement were 37% (29/78) and 42% (28/66), as determined by serum glutamic oxaloacetic (S-GOT) and serum glutamic pyruvic (S-GPT) transaminase values. In contrast, CMV was recovered from 14% (18/127) and 13% (18/141) of infants with normal S-GOT and S-GPT values. The differences in the rates of virus recovery between both groups were more pronounced in infants under three months of age, that is, 5 to 7 times higher rates in infants with liver involvement. Correlation between complement-fixing antibody and liver involvement, however, was not significant, probably because of the influence by maternal antibody. Majority of infants infected with CMV are postulated to involve liver during immediate months after onset of virus excretion."} {"id": "PMID:174246", "title": "A profound deficiency of (CH3-14C)choline sphingomyelin-cleaving enzyme in Niemann-Pick disease type B.", "content": "[Methyl-14C]sphingomyelin was synthesized by the method of Stoffel et al. (1971). A profound deficiency of sphingomyelinase activity was found in liver tissue from two sibling patients with Niemann-Pick disease type B.", "contents": "A profound deficiency of (CH3-14C)choline sphingomyelin-cleaving enzyme in Niemann-Pick disease type B. [Methyl-14C]sphingomyelin was synthesized by the method of Stoffel et al. (1971). A profound deficiency of sphingomyelinase activity was found in liver tissue from two sibling patients with Niemann-Pick disease type B."} {"id": "PMID:174247", "title": "Kinetics of microcolonies of cultured mammalian cells after gamma irradiation.", "content": "The time of cell destruction was determined by pedigree analysis before macrocolony formation immediately after irradiation of gamma rays (400-900 R) in cultured rat hepatoma cells. Cell destruction occurred and was distributed to various generations in proportion to dose. The loss of reproductive integrity resulting in an extinction of a clone was limited in earlier generations, 0 to 2, but the loss of reproductive capacity was observed in later generations. It seems probable that two types of loss of reproduction come from random transmission of lethal signals produced in parent cells irrespective of the pattern of pedigrees.", "contents": "Kinetics of microcolonies of cultured mammalian cells after gamma irradiation. The time of cell destruction was determined by pedigree analysis before macrocolony formation immediately after irradiation of gamma rays (400-900 R) in cultured rat hepatoma cells. Cell destruction occurred and was distributed to various generations in proportion to dose. The loss of reproductive integrity resulting in an extinction of a clone was limited in earlier generations, 0 to 2, but the loss of reproductive capacity was observed in later generations. It seems probable that two types of loss of reproduction come from random transmission of lethal signals produced in parent cells irrespective of the pattern of pedigrees."} {"id": "PMID:174248", "title": "Measurement of fibrinogen degradation products (FDP) in serum of normal and tumor-bearing rats.", "content": "The level of serum fibrinogen degradation products (FDP) in rat was quantified by hemagglutination-inhibition immunoassay which utilized anti-rat-fibrinogen antiserum of rabbit and fibrinogen-coated rat erythrocytes. The sensitivity of this method was high enough to detect minute amounts of serum FDP in rats. The normal value ranged from 1.25 to 10 mug/ml with a mean value of 5.7 mug/ml as expressed as fibrinogen equivalents. The changes in FDP level were noted in tumor-bearing rats which were transplanted subcutaneously with 10(6) tumor cells (AH-109A, a strain of Yoshida rat ascites hepatoma). The FDP level was unchanged in an early stage, elevated to 56 mug/ml on 12th day and to 92 mug/ml on 16th day on an average. These elevations were statistically significant.", "contents": "Measurement of fibrinogen degradation products (FDP) in serum of normal and tumor-bearing rats. The level of serum fibrinogen degradation products (FDP) in rat was quantified by hemagglutination-inhibition immunoassay which utilized anti-rat-fibrinogen antiserum of rabbit and fibrinogen-coated rat erythrocytes. The sensitivity of this method was high enough to detect minute amounts of serum FDP in rats. The normal value ranged from 1.25 to 10 mug/ml with a mean value of 5.7 mug/ml as expressed as fibrinogen equivalents. The changes in FDP level were noted in tumor-bearing rats which were transplanted subcutaneously with 10(6) tumor cells (AH-109A, a strain of Yoshida rat ascites hepatoma). The FDP level was unchanged in an early stage, elevated to 56 mug/ml on 12th day and to 92 mug/ml on 16th day on an average. These elevations were statistically significant."} {"id": "PMID:174249", "title": "Investigation of hexachlorophene for dominant lethal effects in the mouse.", "content": "Hexachlorophene (HCP) was studied for mutagenic effects in the dominant lethal test on mice. Groups of male mice were treated with either 2.5 or 5.0 mg hexachlorophene per kg body weight as a single intraperitoneal injection. Control animals were treated with the propylene glycol vehicle. Each male was mated with 3 untreated females for each of 8 consecutive weeks with the uterus of the females examined at mid-pregnancy for signs of early embryonic death. Treatment did not alter mating capacity and fertility of the males. The administration of hexachlorophene had no influence on pre- or post-implantation losses. An increase in early resorptions among female mice bred to males treated with the reference compound, methyl methanesulfonate (MMS) given a single i.p. injection of 100 mg/kg, indicated the susceptibility of the mouse strain used to a known mutagen. It is concluded that hexachlorophene at maximally tolerated doses is not mutagenic in the dominant lethal test in mice.", "contents": "Investigation of hexachlorophene for dominant lethal effects in the mouse. Hexachlorophene (HCP) was studied for mutagenic effects in the dominant lethal test on mice. Groups of male mice were treated with either 2.5 or 5.0 mg hexachlorophene per kg body weight as a single intraperitoneal injection. Control animals were treated with the propylene glycol vehicle. Each male was mated with 3 untreated females for each of 8 consecutive weeks with the uterus of the females examined at mid-pregnancy for signs of early embryonic death. Treatment did not alter mating capacity and fertility of the males. The administration of hexachlorophene had no influence on pre- or post-implantation losses. An increase in early resorptions among female mice bred to males treated with the reference compound, methyl methanesulfonate (MMS) given a single i.p. injection of 100 mg/kg, indicated the susceptibility of the mouse strain used to a known mutagen. It is concluded that hexachlorophene at maximally tolerated doses is not mutagenic in the dominant lethal test in mice."} {"id": "PMID:174250", "title": "Psychophysiologic effects of early lead exposure.", "content": "In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day.", "contents": "Psychophysiologic effects of early lead exposure. In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day."} {"id": "PMID:174251", "title": "Exposure to an environment containing the aromatic red cedar, Juniperus virginiana: procarcinogenic, enzyme-inducing and insecticidal effects.", "content": "(1) Shavings from the Eastern Red Cedar (Juniperus virginiana) were examined for three diverse biological properties, i.e. enzyme induction, procarcinogenicity and insecticidal activity. (2) The ability of a cedar environment to stimulate liver drug-metabolizing enzymes in mice was confirmed by lowered values for barbiturate sleeping time. (3) In susceptible strains of mice (C3H-Avy, C3H-AvyfB and CBA/J) the use of cedar shavings as bedding increased significantly the incidence of spontaneous tumors of the liver and mammary gland, and also reduced the average time at which tumors appeared. (4) Cedar and some of its derivatives (Oil of Cedarwood, cedrene, cedrol) disrupted the reproductive and developmental cycle of a number of insects, including the Peanut Trash Bug (Elasmolomus sordidus), the Indian Meal Moth (Plodia interpunctella) and the Forage Mite (Tyrophagus putrescentiae).", "contents": "Exposure to an environment containing the aromatic red cedar, Juniperus virginiana: procarcinogenic, enzyme-inducing and insecticidal effects. (1) Shavings from the Eastern Red Cedar (Juniperus virginiana) were examined for three diverse biological properties, i.e. enzyme induction, procarcinogenicity and insecticidal activity. (2) The ability of a cedar environment to stimulate liver drug-metabolizing enzymes in mice was confirmed by lowered values for barbiturate sleeping time. (3) In susceptible strains of mice (C3H-Avy, C3H-AvyfB and CBA/J) the use of cedar shavings as bedding increased significantly the incidence of spontaneous tumors of the liver and mammary gland, and also reduced the average time at which tumors appeared. (4) Cedar and some of its derivatives (Oil of Cedarwood, cedrene, cedrol) disrupted the reproductive and developmental cycle of a number of insects, including the Peanut Trash Bug (Elasmolomus sordidus), the Indian Meal Moth (Plodia interpunctella) and the Forage Mite (Tyrophagus putrescentiae)."} {"id": "PMID:174255", "title": "[Xeroradiographic field control in telecobalt therapy of the cranial and ear-nose-throat regions].", "content": "The possibility of direct field verification by xeroradiography in Co-60-teletherapy of the head- and ENT-regions is described. By the effect of intensified contours, anatomical details may present themselves sufficiently as to make possible an objective verification of the irradiation. The particular advantages of this method consist in the simple handling and in the acceleration of the therapy preparations as well as in the possibility of documentation of the radiotherapeutic treatment. It has to be examined if the xeroradiographical procedure can be utilized for direct verification of the fields in other regions of the body too.", "contents": "[Xeroradiographic field control in telecobalt therapy of the cranial and ear-nose-throat regions]. The possibility of direct field verification by xeroradiography in Co-60-teletherapy of the head- and ENT-regions is described. By the effect of intensified contours, anatomical details may present themselves sufficiently as to make possible an objective verification of the irradiation. The particular advantages of this method consist in the simple handling and in the acceleration of the therapy preparations as well as in the possibility of documentation of the radiotherapeutic treatment. It has to be examined if the xeroradiographical procedure can be utilized for direct verification of the fields in other regions of the body too."} {"id": "PMID:174257", "title": "Enhanced growth of tumor isografts in rats after skin allografting.", "content": "Full-thickness skin grafts from either BN (Ag-B3) or WF (Ag-B2) rats were transplanted to WF recipients of the same sex. Six to seven days after grafting, recipients were challenged with isografts of a chemically induced rat colon carcinoma, NG-W1. In three of four experiments, mean challenge tumor volumes were greater after allografting than after skin isografting. Tumor incidences, however, were no different in rats after skin allograft or isograft placement. When isografts of a polyoma virus-induced sarcoma, P-W13, were used to challenge WF rats after skin grafting, tumor incidence was significantly greater in animals which has received allografts, whether or not they also had been immunized to P-W13 before challenge. Thus, in otherwise untreated inbred rats, grafting of full-thickness skin from donors differing at a major histocompatibility locus led to facilitated growth of solid tumor isografts in animals undergoing allograft rejection.", "contents": "Enhanced growth of tumor isografts in rats after skin allografting. Full-thickness skin grafts from either BN (Ag-B3) or WF (Ag-B2) rats were transplanted to WF recipients of the same sex. Six to seven days after grafting, recipients were challenged with isografts of a chemically induced rat colon carcinoma, NG-W1. In three of four experiments, mean challenge tumor volumes were greater after allografting than after skin isografting. Tumor incidences, however, were no different in rats after skin allograft or isograft placement. When isografts of a polyoma virus-induced sarcoma, P-W13, were used to challenge WF rats after skin grafting, tumor incidence was significantly greater in animals which has received allografts, whether or not they also had been immunized to P-W13 before challenge. Thus, in otherwise untreated inbred rats, grafting of full-thickness skin from donors differing at a major histocompatibility locus led to facilitated growth of solid tumor isografts in animals undergoing allograft rejection."} {"id": "PMID:174258", "title": "[Effect of ultrasound on MG 2+, Na+, K+-ATPase and K+-acetylphosphatase activities of brain subcellular membrane structures].", "content": "Mg2+, Na+, K+-ATPase and K+-acetylphosphatase activities in the brain subcellular membrane structures were studied as affected by ultrasound. Effect of ultrasound depends both on the conditions of sonication and the initial state of membrane fractions. The ATPase activity in the NaI-treated microsomal fraction decreases after sonication. The treatment of microsomal myelin, synaptosomal and mitochondrial fractions with EDTA solutions (5-10(-5)--2-10(-2) M) causes an inhibition in the Mg2+, Na+, K+-ATPase. The ATPase activity of these so-called EDTA-fractions increases after a short-term sonication. Activation of the Mg2+, Na+, K+-ATPase of EDTA-microsomal fraction with a sonication is accompanied by an activation of K+-acetylphosphatase. In contrast to the ATPase activity, the acetylphosphatase one is manifested after a longer effect of ultrasound as well. The maximum of acetylphosphatase activation with sonication coincides with the maximum of Mg2+, Na+, K+-ATPase activation. The content of unmasked SH-groups in the studied fractions decreases after sonication. When EDTA-fractions are affected by sonication, which is accompanied by an increase in the ATPase activity, the number of SH-groups in all the fractions, except for mitochondria, increases.", "contents": "[Effect of ultrasound on MG 2+, Na+, K+-ATPase and K+-acetylphosphatase activities of brain subcellular membrane structures]. Mg2+, Na+, K+-ATPase and K+-acetylphosphatase activities in the brain subcellular membrane structures were studied as affected by ultrasound. Effect of ultrasound depends both on the conditions of sonication and the initial state of membrane fractions. The ATPase activity in the NaI-treated microsomal fraction decreases after sonication. The treatment of microsomal myelin, synaptosomal and mitochondrial fractions with EDTA solutions (5-10(-5)--2-10(-2) M) causes an inhibition in the Mg2+, Na+, K+-ATPase. The ATPase activity of these so-called EDTA-fractions increases after a short-term sonication. Activation of the Mg2+, Na+, K+-ATPase of EDTA-microsomal fraction with a sonication is accompanied by an activation of K+-acetylphosphatase. In contrast to the ATPase activity, the acetylphosphatase one is manifested after a longer effect of ultrasound as well. The maximum of acetylphosphatase activation with sonication coincides with the maximum of Mg2+, Na+, K+-ATPase activation. The content of unmasked SH-groups in the studied fractions decreases after sonication. When EDTA-fractions are affected by sonication, which is accompanied by an increase in the ATPase activity, the number of SH-groups in all the fractions, except for mitochondria, increases."} {"id": "PMID:174263", "title": "Effect of levodopa on urinary bladder.", "content": "Levodopa therapy enhanced the ability of the bladder to store urine in two parkinsonian patients. In vitro canine muscle bath studies with the two major metabolites of levodopa, dopamine and norepinephrine, indicate that the effects of the drug on the peripheral sympathetic nervous system may play a major role in the improvement of urinary symptoms observed with levodopa therapy.", "contents": "Effect of levodopa on urinary bladder. Levodopa therapy enhanced the ability of the bladder to store urine in two parkinsonian patients. In vitro canine muscle bath studies with the two major metabolites of levodopa, dopamine and norepinephrine, indicate that the effects of the drug on the peripheral sympathetic nervous system may play a major role in the improvement of urinary symptoms observed with levodopa therapy."} {"id": "PMID:174259", "title": "[Effect of ACTH on glucose-6-phosphate dehydrogenase and transketolase activity in mitochondria and hyaloplasm of rabbit liver].", "content": "The glucose-6-phosphate dehydrogenase and transketolase activities in mitochondria and hyaloplasm of the rabbit liver were studied as affected by ACTH injected daily in a dose of 10 u/kg of weight for two weeks. It was shown that the activity of glucose-6-phosphate dehydrogenase was unchanged neither in mitochondria nor in hyaloplasm. The transketolase activity in hyaloplasm was not changed as well. But in mitochondria it decreases by 47% (by an increase of sedoheptulose-7-phosphate S-7-P) simultaneously the ribose-5-phosphate (R-5-P) conversion is inhibited by 35%. The ratio of converted R-5-P and formed S-7-P became 2:0.68 (instead of theoretical 2:1). Administration of ACTH has no effect on the total concentration of acid-soluble ribose-containing compounds in both mitochondria and hyaloplasm.", "contents": "[Effect of ACTH on glucose-6-phosphate dehydrogenase and transketolase activity in mitochondria and hyaloplasm of rabbit liver]. The glucose-6-phosphate dehydrogenase and transketolase activities in mitochondria and hyaloplasm of the rabbit liver were studied as affected by ACTH injected daily in a dose of 10 u/kg of weight for two weeks. It was shown that the activity of glucose-6-phosphate dehydrogenase was unchanged neither in mitochondria nor in hyaloplasm. The transketolase activity in hyaloplasm was not changed as well. But in mitochondria it decreases by 47% (by an increase of sedoheptulose-7-phosphate S-7-P) simultaneously the ribose-5-phosphate (R-5-P) conversion is inhibited by 35%. The ratio of converted R-5-P and formed S-7-P became 2:0.68 (instead of theoretical 2:1). Administration of ACTH has no effect on the total concentration of acid-soluble ribose-containing compounds in both mitochondria and hyaloplasm."} {"id": "PMID:174264", "title": "Interaction of ultrasound with neoplastic tissue. II. Systemic effects after local sonic irradiation.", "content": "Local sonic irradiation was applied to subcutaneously implanted Furth-Columbia rat Wilms' tumor. The weight and the rate of tritiated thymidine uptake were measured in host organs distal to the application field. Kidney and spleen weights were inhibited by the Wilms' tumor, and sonication of the tumor removed all or part of this inhibition. Liver weight was increased after sonication of tumor-bearing rats but not in nontumor-bearing rats. This may have been a response to tumor-specific substances released into the circulation by sonic destruction of tumor tissue. The adrenals enlarged as a response to the stresses of both tumor-bearing and of sonication. Animals were implanted on both sides with the Wilms' tumor and on without any break in the growth curve while the sonicated right tumor was inhibited. These data suggest that the therapeutic effect of ultrasound is due solely to local factors and that systemic sequelae of some irradiation are unrelated to tumor inhibition.", "contents": "Interaction of ultrasound with neoplastic tissue. II. Systemic effects after local sonic irradiation. Local sonic irradiation was applied to subcutaneously implanted Furth-Columbia rat Wilms' tumor. The weight and the rate of tritiated thymidine uptake were measured in host organs distal to the application field. Kidney and spleen weights were inhibited by the Wilms' tumor, and sonication of the tumor removed all or part of this inhibition. Liver weight was increased after sonication of tumor-bearing rats but not in nontumor-bearing rats. This may have been a response to tumor-specific substances released into the circulation by sonic destruction of tumor tissue. The adrenals enlarged as a response to the stresses of both tumor-bearing and of sonication. Animals were implanted on both sides with the Wilms' tumor and on without any break in the growth curve while the sonicated right tumor was inhibited. These data suggest that the therapeutic effect of ultrasound is due solely to local factors and that systemic sequelae of some irradiation are unrelated to tumor inhibition."} {"id": "PMID:174265", "title": "A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.", "content": "A man now 22 years of age had slow psychomotor development about 6 months after birth and developed intermittent corneal clouding at about 18 months. He developed truncal ataxia, hypotonia of the limbs combined with spasticity, and active deep reflexes. These have not progressed. His skeleton and facies are normal. Between his first and thriteenth year he developed sev ere optic atrophy, absence of retinal blood vessels, and an extinguished electroretinogram. Biochemical analysis of cultured fibroblasts indicated no lysosomal hydrolase deficiency; cellular metachromasia was absent and there was no mucopolysaccharidoses. Ultrastructural studies indicated single membrane vacuoles containing lamellated membranes and a polymorphous substance in tissue cultured cells and conjunctiva.", "contents": "A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration. A man now 22 years of age had slow psychomotor development about 6 months after birth and developed intermittent corneal clouding at about 18 months. He developed truncal ataxia, hypotonia of the limbs combined with spasticity, and active deep reflexes. These have not progressed. His skeleton and facies are normal. Between his first and thriteenth year he developed sev ere optic atrophy, absence of retinal blood vessels, and an extinguished electroretinogram. Biochemical analysis of cultured fibroblasts indicated no lysosomal hydrolase deficiency; cellular metachromasia was absent and there was no mucopolysaccharidoses. Ultrastructural studies indicated single membrane vacuoles containing lamellated membranes and a polymorphous substance in tissue cultured cells and conjunctiva."} {"id": "PMID:174266", "title": "Epidemic keratoconjunctivitis due to adenovirus type 19.", "content": "A new type of epidemic kerotoconjunctivitis, caused by adenovirus type 19, is currently present in this country. It can be spread by tonometry, but in this report, appeared to be more likely to be spread by finger to eye contact.", "contents": "Epidemic keratoconjunctivitis due to adenovirus type 19. A new type of epidemic kerotoconjunctivitis, caused by adenovirus type 19, is currently present in this country. It can be spread by tonometry, but in this report, appeared to be more likely to be spread by finger to eye contact."} {"id": "PMID:174262", "title": "[Determination of riboflavin kinase activity in yeast].", "content": "It is established that the main reason of the riboflavin kinase (RFK, EC 2.7.1.26) low specific activity in the cell-free extracts of the yeast Pichia guillermondii Wickerham ATCC 9058 is the presence of alkaline phosphatase (EC 3.1.3.1), effectively destructing flaven mononucleotide. By chromatography of the cell-free extracts of P. guillermondii on DEAE-Sephadex A-50, CM-Sphadex C-50, CM-cellulose, Sephadexes G-75 and G-100 RFK and alkaline phosphatase may be separated completely. Any of these procedures results in a several times increase of the RFK activity as compared with the initial preparation. One failed to obtain a similar effect by fractionation of the extracts with amminium sulphate and by hydroxylapatite chromatography. A simple method is developed for determining the activity of RFK in the cell-free extracts of yeast on the basis of negative adsorption of this enzyme on DEAE-Sephadex A-50. A selective inhibition of alkaline phosphatase by ions Be2+ and F- yields a less satisfactory result. The data are presented on the PFK activity of certain species of flavinogenic (Pichia guillermondii, Torulopsis camdida) and non-flavinogenic (Pichia ohmeri, Candida utilis, Saccharomyces cervisiae) yeast.", "contents": "[Determination of riboflavin kinase activity in yeast]. It is established that the main reason of the riboflavin kinase (RFK, EC 2.7.1.26) low specific activity in the cell-free extracts of the yeast Pichia guillermondii Wickerham ATCC 9058 is the presence of alkaline phosphatase (EC 3.1.3.1), effectively destructing flaven mononucleotide. By chromatography of the cell-free extracts of P. guillermondii on DEAE-Sephadex A-50, CM-Sphadex C-50, CM-cellulose, Sephadexes G-75 and G-100 RFK and alkaline phosphatase may be separated completely. Any of these procedures results in a several times increase of the RFK activity as compared with the initial preparation. One failed to obtain a similar effect by fractionation of the extracts with amminium sulphate and by hydroxylapatite chromatography. A simple method is developed for determining the activity of RFK in the cell-free extracts of yeast on the basis of negative adsorption of this enzyme on DEAE-Sephadex A-50. A selective inhibition of alkaline phosphatase by ions Be2+ and F- yields a less satisfactory result. The data are presented on the PFK activity of certain species of flavinogenic (Pichia guillermondii, Torulopsis camdida) and non-flavinogenic (Pichia ohmeri, Candida utilis, Saccharomyces cervisiae) yeast."} {"id": "PMID:174260", "title": "[Carbohydrate metabolism in the liver in acute ischemia].", "content": "The article deals with oxidation of different substrates, intensity of glycolytic and glycogenolytic processes in mitochondria and homogenates of dog liver with its 2-hour exclusion from circulation under conditions of endotracheal ether-oxygen narcosis. It was established that already 30-60-minute ischemia causes a decrease in intensity of succinate, alpha-ketoglutarate oxidation and acceptor respiration, inhibiton in the activity of the citrate cycle enzymes; succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, isocytrate dehydrogenase. The activity of NAD-dependent malate dehydrogenasedehydrogenase and Mg2+-ATPase as well as intensity of NADN oxidation in mitochondria increase. After 2-hour ischemia the activity of Mg2+-ATPase, cytochrome oxidase and peroxidase lowers. A sharply developed glycogenolysis is accompanied by inhibition of phosphorylase activity and a two-fold stimulation of the glycolytic reactions. Peculiarities in regulation of enzymatic reactions under conditions of ischemia and their role in origin of metabolism disturbances in the liver are under discussion.", "contents": "[Carbohydrate metabolism in the liver in acute ischemia]. The article deals with oxidation of different substrates, intensity of glycolytic and glycogenolytic processes in mitochondria and homogenates of dog liver with its 2-hour exclusion from circulation under conditions of endotracheal ether-oxygen narcosis. It was established that already 30-60-minute ischemia causes a decrease in intensity of succinate, alpha-ketoglutarate oxidation and acceptor respiration, inhibiton in the activity of the citrate cycle enzymes; succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, isocytrate dehydrogenase. The activity of NAD-dependent malate dehydrogenasedehydrogenase and Mg2+-ATPase as well as intensity of NADN oxidation in mitochondria increase. After 2-hour ischemia the activity of Mg2+-ATPase, cytochrome oxidase and peroxidase lowers. A sharply developed glycogenolysis is accompanied by inhibition of phosphorylase activity and a two-fold stimulation of the glycolytic reactions. Peculiarities in regulation of enzymatic reactions under conditions of ischemia and their role in origin of metabolism disturbances in the liver are under discussion."} {"id": "PMID:174261", "title": "[Effect of detergents and ultrasound on NAD-glycohydrolase activity in rat liver cell nuclei].", "content": "The NAD-glycohydrolase activity of freshly isolated adult rat liver cells nuclei was studied as affected by the ionic (dodecyl sulphate and deoxicholate) and non-ionic (Triton X-100 and digitonin) detergents as well as by ultrasound (15 and 22 kHz). The obtained data permit the detergents to be divided according to the character of their effects on the nuclear NADase activity into \"decreasing\" and \"increasing\" ones. Dodecyl sulphate and to a less extent deoxicholate are in the first group of the detergents. Triton X-100 and much more digitonin are in the second one. Sonification of the rat liver cells nuclei (15 and 22 kHz) from 3-10 s and further induced a decrease in the NADase activity with its subsequent complete loss. The treatment of the intact nuclei suspension with DNase leads to a 50% decrease in the NADase activity and the treatment of the sonificated nuclei suspension-- to a complete loss of the activity. Undet these conditions RNase does not affect the NADase activity.", "contents": "[Effect of detergents and ultrasound on NAD-glycohydrolase activity in rat liver cell nuclei]. The NAD-glycohydrolase activity of freshly isolated adult rat liver cells nuclei was studied as affected by the ionic (dodecyl sulphate and deoxicholate) and non-ionic (Triton X-100 and digitonin) detergents as well as by ultrasound (15 and 22 kHz). The obtained data permit the detergents to be divided according to the character of their effects on the nuclear NADase activity into \"decreasing\" and \"increasing\" ones. Dodecyl sulphate and to a less extent deoxicholate are in the first group of the detergents. Triton X-100 and much more digitonin are in the second one. Sonification of the rat liver cells nuclei (15 and 22 kHz) from 3-10 s and further induced a decrease in the NADase activity with its subsequent complete loss. The treatment of the intact nuclei suspension with DNase leads to a 50% decrease in the NADase activity and the treatment of the sonificated nuclei suspension-- to a complete loss of the activity. Undet these conditions RNase does not affect the NADase activity."} {"id": "PMID:174277", "title": "[Study of the symplast-forming activity of terpene and standard strains of Aujeszky's disease virus].", "content": "Studied were the cellular changes and, more specifically, the production of symplasts as a particular form of manifesting the cytopathic effect of some strains of the Aujezsky's virus. Experiments with eight strains of the virus in tissue cultures confirmed the concept of a number of authors that in given tissue cultures virulent strains show a well pronounced trent toward the formation of symplasts containing numerous nuclei, while the latent strains stimulate the production of sporadic, rounded giant cells with a few nuclei in the aggregated cytoplasm. In the course of the investigations the primary cultures of rabbit kidney proved very suitable to demonstrate the presence of Aujeszky's disease and differentiate latent and virulent strains because of the cultures exceptional receptivity to the Aujeszky virus.", "contents": "[Study of the symplast-forming activity of terpene and standard strains of Aujeszky's disease virus]. Studied were the cellular changes and, more specifically, the production of symplasts as a particular form of manifesting the cytopathic effect of some strains of the Aujezsky's virus. Experiments with eight strains of the virus in tissue cultures confirmed the concept of a number of authors that in given tissue cultures virulent strains show a well pronounced trent toward the formation of symplasts containing numerous nuclei, while the latent strains stimulate the production of sporadic, rounded giant cells with a few nuclei in the aggregated cytoplasm. In the course of the investigations the primary cultures of rabbit kidney proved very suitable to demonstrate the presence of Aujeszky's disease and differentiate latent and virulent strains because of the cultures exceptional receptivity to the Aujeszky virus."} {"id": "PMID:174278", "title": "[Porperties of a strain of Herpesvirus suis isolated in cases with various epizootologic and clinical courses of the disease].", "content": "A varying epizootologic, clinical and morphologic picture was established in studying the course of the disease on six pig-breeding farms. The isolated strains showed differences in their virulence, cultural properties and physicochemical behaviour. Two of them had lowered virulence, and one showed affinity to the respiratory organs which corresponded to the peculiarities and course of the disease. It is concluded that the interaction between the virulence of the strains and the herd immunity results in the varying epizootologic course of the disease.", "contents": "[Porperties of a strain of Herpesvirus suis isolated in cases with various epizootologic and clinical courses of the disease]. A varying epizootologic, clinical and morphologic picture was established in studying the course of the disease on six pig-breeding farms. The isolated strains showed differences in their virulence, cultural properties and physicochemical behaviour. Two of them had lowered virulence, and one showed affinity to the respiratory organs which corresponded to the peculiarities and course of the disease. It is concluded that the interaction between the virulence of the strains and the herd immunity results in the varying epizootologic course of the disease."} {"id": "PMID:174279", "title": "[Use of the direct immunofluorescence method for determination of the TGE viral antigen in swine].", "content": "Followed up were the appearance and accumulation of the transmissive gastroenteritis (TGE) virus antigen in infected cells of pig kidney and thyroid. Used were specific conjugates, such introduced by the authors and some imported from Czechoslovakia. The cell cultures were infected with strains of the TGE virus, isolated in Bulgaria or supplied from Czechoslovakia. It was found that the Bulgarian strains were the same as those from Czechoslovakia and the United States. A viral antigen was found as early as the sixth hour following the infection of the cell cultures and it appeared under the form of cytoplasmatic yellow-green fluorescence. By the 12th, and up to the 18th hour the number of the specifically fluorescing cells as well as the intensity of fluorescence itself increased. Highest values in this respect were noticed in the interval between the 36th and 48th hour after the cultures had been infected.", "contents": "[Use of the direct immunofluorescence method for determination of the TGE viral antigen in swine]. Followed up were the appearance and accumulation of the transmissive gastroenteritis (TGE) virus antigen in infected cells of pig kidney and thyroid. Used were specific conjugates, such introduced by the authors and some imported from Czechoslovakia. The cell cultures were infected with strains of the TGE virus, isolated in Bulgaria or supplied from Czechoslovakia. It was found that the Bulgarian strains were the same as those from Czechoslovakia and the United States. A viral antigen was found as early as the sixth hour following the infection of the cell cultures and it appeared under the form of cytoplasmatic yellow-green fluorescence. By the 12th, and up to the 18th hour the number of the specifically fluorescing cells as well as the intensity of fluorescence itself increased. Highest values in this respect were noticed in the interval between the 36th and 48th hour after the cultures had been infected."} {"id": "PMID:174280", "title": "[Experience in the complex vaccination of birds against pseudoplague, infectious laryngotracheitis and diphtheria pox].", "content": "The immunity was studied as conferred by the simultaneous vaccination against Newcastle disease (strain La Sota), infectious laryngotracheitis (strain \"TsNIIP\"), and fowl pox (strain FK), applied at different sites. The vaccine against Newcastle disease was diluted at 1 : 10 and was applied nasally through instilling one drop in each orifice. When it was mixed with a vaccine against infectious laryngotracheitis at a ratio of 1 : 1 it was applied via the cloaca or nasally, orally, muscularly or through the ocular sinus. The vaccine against fowl pox was applied at the same time at dilution of 1 : 50 through the wing web. The effectiveness of the immunity conferred was checked through challenge infection, haemagglutination inhibition reactions, and virus-neutralization in chick embryos. It is stated that the resulting stress accompanying every vaccination was not stronger with the combination used than that in other cases. This was also an advantage over the alternative of administering the vaccines alone. The immunity against the three diseases, obtained at the simultaneous application of the vaccines, did not differ from that resulting from administering the vaccines alone. This, XXX indisputably, points to the fact that the method is equally useful from an epizootiologic and an economic standpoint.", "contents": "[Experience in the complex vaccination of birds against pseudoplague, infectious laryngotracheitis and diphtheria pox]. The immunity was studied as conferred by the simultaneous vaccination against Newcastle disease (strain La Sota), infectious laryngotracheitis (strain \"TsNIIP\"), and fowl pox (strain FK), applied at different sites. The vaccine against Newcastle disease was diluted at 1 : 10 and was applied nasally through instilling one drop in each orifice. When it was mixed with a vaccine against infectious laryngotracheitis at a ratio of 1 : 1 it was applied via the cloaca or nasally, orally, muscularly or through the ocular sinus. The vaccine against fowl pox was applied at the same time at dilution of 1 : 50 through the wing web. The effectiveness of the immunity conferred was checked through challenge infection, haemagglutination inhibition reactions, and virus-neutralization in chick embryos. It is stated that the resulting stress accompanying every vaccination was not stronger with the combination used than that in other cases. This was also an advantage over the alternative of administering the vaccines alone. The immunity against the three diseases, obtained at the simultaneous application of the vaccines, did not differ from that resulting from administering the vaccines alone. This, XXX indisputably, points to the fact that the method is equally useful from an epizootiologic and an economic standpoint."} {"id": "PMID:174281", "title": "[Determination of the subtype membership of the epizootic foot-and-mouth disease virus by means of the agar gel diffusion test].", "content": "Comparative studies were carried out by means of the agar gel-diffusion technique (AGDT) to establish the antigenic identity between the epizootic foot-and-mouth disease strain (the Nch/73 representative strain) and the standard viruses of type A. The epizootic strain was found to belong to the subtype group A5. Discussed is the usefulness of AGDT in determining the antigenic relations between the foot-and-mouth disease viruses.", "contents": "[Determination of the subtype membership of the epizootic foot-and-mouth disease virus by means of the agar gel diffusion test]. Comparative studies were carried out by means of the agar gel-diffusion technique (AGDT) to establish the antigenic identity between the epizootic foot-and-mouth disease strain (the Nch/73 representative strain) and the standard viruses of type A. The epizootic strain was found to belong to the subtype group A5. Discussed is the usefulness of AGDT in determining the antigenic relations between the foot-and-mouth disease viruses."} {"id": "PMID:174282", "title": "[Changes in carbohydrate metabolism in hens experimentally infected with Pasteurella multocida kokoshki].", "content": "Studied were the concentration of blood sugar, the activity of glucose-6-phosphatase and glucose-6-phosphatedehydrogenase, and the level of glycogen in the liver of P. multocida infected chickens. An abrupt decrease of the liver glycogen was found as well as a negligible rise of the blood sugar. The activity of glucose-6-phosphatase remained unchanged, and that of glucose-6-dehydrogenase was twice as high. It is concluded that the intense exhaustion of liver glycogen is in connection with the activation of the pentosephosphate pathway.", "contents": "[Changes in carbohydrate metabolism in hens experimentally infected with Pasteurella multocida kokoshki]. Studied were the concentration of blood sugar, the activity of glucose-6-phosphatase and glucose-6-phosphatedehydrogenase, and the level of glycogen in the liver of P. multocida infected chickens. An abrupt decrease of the liver glycogen was found as well as a negligible rise of the blood sugar. The activity of glucose-6-phosphatase remained unchanged, and that of glucose-6-dehydrogenase was twice as high. It is concluded that the intense exhaustion of liver glycogen is in connection with the activation of the pentosephosphate pathway."} {"id": "PMID:174283", "title": "[Ultrastructure and morphogenesis of ceroid pigment. II. Late changes of lysosomes in Kupffer cells of rat liver after phagocytosis of unsaturated lipids (author's transl)].", "content": "Wistar rats were injected intravenously with cod liver oil emulsion. The lipid droplets ere phagocytized by Kupffer cells and stored in lysosomes. The transformation of these lipid-containing lysosomes into ceroid pigment granules was studied electron-microscopically and cytochemically for a period of 12 weeks after the injection. The lipid droplets enclosed in lysosomes show an increasing and continous condensation from the periphery towards the center due to oxidation and polymerization of unsaturated fatty acids. During the first week almost the total amount of the stored lipids is transformed into an amorphous, highly electron-dense material which disintegrates into cloddy and globular fragments during the following time. The fragments are embedded in a fine granular, slightly electron-dense matrix showing a marked activity of acid phosphatase. The lysosomal structures which contain remnants of condensed oxidized and polymerized lipids are the electron-microscopic equivalent of the granules as seen by light microscopy. These lipids, which have been changed in their molecular structure, cannot be hydrolized by lysosomal enzymes. They remain as an indigestible material, as a waste product in lysosomal residual bodies. Both lipofuscin and ceroid are lysosomal structures containing oxidized and polymerized lipids. The differences between these lipogenous pigments are due to their different formal and causal genesis. Lipofuscin develops in parenchymal and muscle cells by autophagocytosis and by subsequent oxidation and polymerization of segregated membrane lipids. Ceroid is formed in macrophages by heterophagocytosis of unsaturated lipid material which is also oxidized and polymerized.", "contents": "[Ultrastructure and morphogenesis of ceroid pigment. II. Late changes of lysosomes in Kupffer cells of rat liver after phagocytosis of unsaturated lipids (author's transl)]. Wistar rats were injected intravenously with cod liver oil emulsion. The lipid droplets ere phagocytized by Kupffer cells and stored in lysosomes. The transformation of these lipid-containing lysosomes into ceroid pigment granules was studied electron-microscopically and cytochemically for a period of 12 weeks after the injection. The lipid droplets enclosed in lysosomes show an increasing and continous condensation from the periphery towards the center due to oxidation and polymerization of unsaturated fatty acids. During the first week almost the total amount of the stored lipids is transformed into an amorphous, highly electron-dense material which disintegrates into cloddy and globular fragments during the following time. The fragments are embedded in a fine granular, slightly electron-dense matrix showing a marked activity of acid phosphatase. The lysosomal structures which contain remnants of condensed oxidized and polymerized lipids are the electron-microscopic equivalent of the granules as seen by light microscopy. These lipids, which have been changed in their molecular structure, cannot be hydrolized by lysosomal enzymes. They remain as an indigestible material, as a waste product in lysosomal residual bodies. Both lipofuscin and ceroid are lysosomal structures containing oxidized and polymerized lipids. The differences between these lipogenous pigments are due to their different formal and causal genesis. Lipofuscin develops in parenchymal and muscle cells by autophagocytosis and by subsequent oxidation and polymerization of segregated membrane lipids. Ceroid is formed in macrophages by heterophagocytosis of unsaturated lipid material which is also oxidized and polymerized."} {"id": "PMID:174284", "title": "Intraalveolar foam cells associated with lipidosis-like alterations in lung and liver of rats treated with tricyclic psychotropic drugs.", "content": "Histological, histochemical, and ultrastructural examinations were performed on pulmonary and hepatic tissues of rats after prolonged oral treatment with several tricyclic antidepressants and two neuroleptics, which are all of amphiphilic character. The antidepressants ipindole, imipramine, clomipramine, 1-chloro-amitriptyline, and 1-chloro-10,11-dehydro-amitriptyline were found to cause an accumulation of intraalveolar foam cells accompanied by the formation of abnormal lamellated and crystalloid cytoplasmic inclusions in most pulmonary and hepatic cell types. The ultrastructural and histochemical findings in both tissues point to generalized, abnormal intracellular storage of polar lipids, i.e. to drug-induced lipidosis. The foam cells are not regarded as an isolated pulmonary alteration but rather as an easily obtainable indication of generalized lipidosis, under the present conditions. They are thought to represent alveolar macrophages stuffed with non-digestible phospholipids. On the other hand, the tricyclic antidepressants noxiptiline and amitriptyline, and the neuroleptics chlorpromazine and thioridazine caused neither formation of foam cells nor of any lipidosis-like ultrastructural alterations. These negative results are tentatively ascribed to a more rapid biotransformation of the amphiphilic drug molecules into more hydrophilic metabolites which no longer have a high affinity to polar lipids. Two main conclusions can be drawn from the present ovservations: (1) Intraalveolar foam cells must not be regarded as a fortuitous alteration but rather as a first indication of generalized phospholipidosis, when they are found in animals treated with an amphiphilic drug. (2) Closely related compounds of amphiphilic character do not necessarily have the same potency to induce a phospholipidosis under in vivo conditions.", "contents": "Intraalveolar foam cells associated with lipidosis-like alterations in lung and liver of rats treated with tricyclic psychotropic drugs. Histological, histochemical, and ultrastructural examinations were performed on pulmonary and hepatic tissues of rats after prolonged oral treatment with several tricyclic antidepressants and two neuroleptics, which are all of amphiphilic character. The antidepressants ipindole, imipramine, clomipramine, 1-chloro-amitriptyline, and 1-chloro-10,11-dehydro-amitriptyline were found to cause an accumulation of intraalveolar foam cells accompanied by the formation of abnormal lamellated and crystalloid cytoplasmic inclusions in most pulmonary and hepatic cell types. The ultrastructural and histochemical findings in both tissues point to generalized, abnormal intracellular storage of polar lipids, i.e. to drug-induced lipidosis. The foam cells are not regarded as an isolated pulmonary alteration but rather as an easily obtainable indication of generalized lipidosis, under the present conditions. They are thought to represent alveolar macrophages stuffed with non-digestible phospholipids. On the other hand, the tricyclic antidepressants noxiptiline and amitriptyline, and the neuroleptics chlorpromazine and thioridazine caused neither formation of foam cells nor of any lipidosis-like ultrastructural alterations. These negative results are tentatively ascribed to a more rapid biotransformation of the amphiphilic drug molecules into more hydrophilic metabolites which no longer have a high affinity to polar lipids. Two main conclusions can be drawn from the present ovservations: (1) Intraalveolar foam cells must not be regarded as a fortuitous alteration but rather as a first indication of generalized phospholipidosis, when they are found in animals treated with an amphiphilic drug. (2) Closely related compounds of amphiphilic character do not necessarily have the same potency to induce a phospholipidosis under in vivo conditions."} {"id": "PMID:174285", "title": "Myeloid bodies formation in triparanol treated cultured cells.", "content": "Cultured cells (chicken embryo liver cells and rat embryo fibroblasts) were treated with triparanol (MER-29) for various lengths of time. Both types of cells have developed numerous membranous whorls-myeloid bodies in the cytoplasm. Various stages in myeloid bodies development are described. Acid phosphatase activity was cytochemically demonstrated within the myeloid bodies, indicating their lysosmal nature. This activity appeared only at a late stage of the myeloid bodies formation.", "contents": "Myeloid bodies formation in triparanol treated cultured cells. Cultured cells (chicken embryo liver cells and rat embryo fibroblasts) were treated with triparanol (MER-29) for various lengths of time. Both types of cells have developed numerous membranous whorls-myeloid bodies in the cytoplasm. Various stages in myeloid bodies development are described. Acid phosphatase activity was cytochemically demonstrated within the myeloid bodies, indicating their lysosmal nature. This activity appeared only at a late stage of the myeloid bodies formation."} {"id": "PMID:174305", "title": "[Clinical characteristics of unclassified soft tissue tumors].", "content": "The authors have analysed the data obtained in 462 patients with malignant tumors of soft tissues, operated upon in this Institute during the period of 1948-1973, inclusively. Some features of the clinical picture were revealed that might allow the investigators in some cases to suggest the histological type of the tumor, referred to as a nonclassified group. Such pinpointing further of the diagnosis is of some practical value from the point of view of selecting indications to some or other method of treatment in patients with malignant tumors of soft tissues.", "contents": "[Clinical characteristics of unclassified soft tissue tumors]. The authors have analysed the data obtained in 462 patients with malignant tumors of soft tissues, operated upon in this Institute during the period of 1948-1973, inclusively. Some features of the clinical picture were revealed that might allow the investigators in some cases to suggest the histological type of the tumor, referred to as a nonclassified group. Such pinpointing further of the diagnosis is of some practical value from the point of view of selecting indications to some or other method of treatment in patients with malignant tumors of soft tissues."} {"id": "PMID:174301", "title": "[Inositol containing phospholipids in brain and liver tissue of rats in prolonged alcoholic intoxication].", "content": "In brain and liver tissue of rats, treated repeatedly with alcohol, alterations in content of total phospholipids and polyphosphoinositols were reproducibly different. In the tissues studied content of polyphosphoinositols were distinctly decreased. Independent function of phosphoinositols in tissue metabolism as an auxiliary energy system in addition to the universal adenylate system is considered. These concepts are in agreement with observations on development of rough morphological alterations (fatty degeneration) in liver tissue. The fatty degeneration developed in the liver tissue in response to deficiency of oxidative potential in the organ.", "contents": "[Inositol containing phospholipids in brain and liver tissue of rats in prolonged alcoholic intoxication]. In brain and liver tissue of rats, treated repeatedly with alcohol, alterations in content of total phospholipids and polyphosphoinositols were reproducibly different. In the tissues studied content of polyphosphoinositols were distinctly decreased. Independent function of phosphoinositols in tissue metabolism as an auxiliary energy system in addition to the universal adenylate system is considered. These concepts are in agreement with observations on development of rough morphological alterations (fatty degeneration) in liver tissue. The fatty degeneration developed in the liver tissue in response to deficiency of oxidative potential in the organ."} {"id": "PMID:174306", "title": "[Tomizine--a new inhibitor of folate metabolism enzymes possessing an antitumor activity].", "content": "In the experiments on enzymic systems functioning in the metabolism of folic acid and on transplantable tumors in animals the preparation thomizine (chlorohydrate 4-methoxy-6-aminopyrimido (4,5-b) (1,4) thiazine) was worked out. Thomizine, as well as the known antimetabolite of folic acid-methotrexate, suppresses the activity of dihydrofolate reductase, but contrary to it suppresses FAP enzymic system, inhibiting aminopterin in the organism. Thomizine differes from methotrexate by another spectrum of antitumor effect, selective suppression of the tumor tissue growth, compared with the normal in vitro, it does not inhibit leucopoiesis, shows less toxicity and insignificant cumulative properties.", "contents": "[Tomizine--a new inhibitor of folate metabolism enzymes possessing an antitumor activity]. In the experiments on enzymic systems functioning in the metabolism of folic acid and on transplantable tumors in animals the preparation thomizine (chlorohydrate 4-methoxy-6-aminopyrimido (4,5-b) (1,4) thiazine) was worked out. Thomizine, as well as the known antimetabolite of folic acid-methotrexate, suppresses the activity of dihydrofolate reductase, but contrary to it suppresses FAP enzymic system, inhibiting aminopterin in the organism. Thomizine differes from methotrexate by another spectrum of antitumor effect, selective suppression of the tumor tissue growth, compared with the normal in vitro, it does not inhibit leucopoiesis, shows less toxicity and insignificant cumulative properties."} {"id": "PMID:174302", "title": "[Study of mechanisms of regulation of disulphide reductase in mouse liver].", "content": "An increase in activity of disulphide reductase system (DRS) in supernatant of liver tissue was caused by 3',5'-AMP, ATP, GTP, UTP, Mg2+, Ca2+, EDTA, protamine, noradrenaline and F-. The effect was connected with arsenite resistant fraction of DRS. After rapid homogenization the effect of noradrenaline disappeared and the effects of ATP, GTP, UTP and Ca2+ were distinctly decreased. Treatment with adsorbents prevented the effects of 3',5,-AMP, ATP and EDTA and markedly decreased the effects of protamine and Mg2+. A protein inhibitor of protein kinase prevented completely the activation of DRS with 3',5'-AMP, ATP, GTP, UTP and noradrenaline and distinctly decreased the effect of protamine, Mg2+ and Ca2+ but did not alter the influence of EDTA. Addition of 2',3'-AMP blocked the effect of 3',5-AMP, ATP and Mg2+ but did not influence the effect of protamine and EDTA. The data obtained suggest that protein kinase participated in activation of DRS by most of the regulators.", "contents": "[Study of mechanisms of regulation of disulphide reductase in mouse liver]. An increase in activity of disulphide reductase system (DRS) in supernatant of liver tissue was caused by 3',5'-AMP, ATP, GTP, UTP, Mg2+, Ca2+, EDTA, protamine, noradrenaline and F-. The effect was connected with arsenite resistant fraction of DRS. After rapid homogenization the effect of noradrenaline disappeared and the effects of ATP, GTP, UTP and Ca2+ were distinctly decreased. Treatment with adsorbents prevented the effects of 3',5,-AMP, ATP and EDTA and markedly decreased the effects of protamine and Mg2+. A protein inhibitor of protein kinase prevented completely the activation of DRS with 3',5'-AMP, ATP, GTP, UTP and noradrenaline and distinctly decreased the effect of protamine, Mg2+ and Ca2+ but did not alter the influence of EDTA. Addition of 2',3'-AMP blocked the effect of 3',5-AMP, ATP and Mg2+ but did not influence the effect of protamine and EDTA. The data obtained suggest that protein kinase participated in activation of DRS by most of the regulators."} {"id": "PMID:174303", "title": "[Effect of pyridoxine on patterns of lipid metabolism in patients with alimentary obesity].", "content": "Studies of patients with alimentary-metabolic obesity, which were treated with pyridoxine and were maintained on a reduced diet, revealed a normalizing effect of the vitamin on some patterns of lipid metabolism. In patients, treated with pyridoxine, body weight, content of total lipids, cholesterol, phospholipids, glycerids and beta-lipoproteins in blood serum were decreased more distinctly as compared with patients, which were only maintained on a reduced diet. In hyperlipidaemia the positive effect of pyridoxine was more pronounced than in the cases with normal content of lipids in blood.", "contents": "[Effect of pyridoxine on patterns of lipid metabolism in patients with alimentary obesity]. Studies of patients with alimentary-metabolic obesity, which were treated with pyridoxine and were maintained on a reduced diet, revealed a normalizing effect of the vitamin on some patterns of lipid metabolism. In patients, treated with pyridoxine, body weight, content of total lipids, cholesterol, phospholipids, glycerids and beta-lipoproteins in blood serum were decreased more distinctly as compared with patients, which were only maintained on a reduced diet. In hyperlipidaemia the positive effect of pyridoxine was more pronounced than in the cases with normal content of lipids in blood."} {"id": "PMID:174304", "title": "[A micromethod for determination of the adenylate cyclase activity by chromatography on silufol UV-254 plates].", "content": "A method is developed for micro-scale separation of the products of enzymatic degradation of ATP (ADP, 5'-AMP, adenosine 3',5'-cytophosphate, adenosine and adenine) by one-dimentional thin-layer chromatography on Silufol UV-254 plates. The method is applicable for determination of activity of adenylate cyclase and of other enzymes involved in metabolism of adenylic derivatives, including the diesterase of 3',5'-cyclic AMP.", "contents": "[A micromethod for determination of the adenylate cyclase activity by chromatography on silufol UV-254 plates]. A method is developed for micro-scale separation of the products of enzymatic degradation of ATP (ADP, 5'-AMP, adenosine 3',5'-cytophosphate, adenosine and adenine) by one-dimentional thin-layer chromatography on Silufol UV-254 plates. The method is applicable for determination of activity of adenylate cyclase and of other enzymes involved in metabolism of adenylic derivatives, including the diesterase of 3',5'-cyclic AMP."} {"id": "PMID:174308", "title": "[Several properties of the nucleic acide of nuclei and mitochondria from hepatoma induced by N-nitroso-N-diethylamine].", "content": "The work was undertaken to estimate quantitatively the functional activity of tumor cell genome and possible variations in the relationship between nuclear genome and mitochondrial genetic determinants in tumor cell. For this purpose in mice C3HA tumors of hepatocellular origin were induced with N-nitroso-N-diethylamine, tissues of one of which were subjected to successive isologous transplantation during the period over 3 years. Normal hepatic tissues were taken for the control. As a result of a series of independent experiments (actinomycin D spectrophotometric titration, acridine orange binding, template activity, nuclear RNA/DNA hybridization) the results were obtained indicating a decrease in the amount of active loci in tumor hepatocytes genome. Hybridization data also indicate that in the tumor the derepression of chromosomal genes responsible for the genetic control over mitochondria and a non-regulated de-repression of mitochondrial genetic determinants take place.", "contents": "[Several properties of the nucleic acide of nuclei and mitochondria from hepatoma induced by N-nitroso-N-diethylamine]. The work was undertaken to estimate quantitatively the functional activity of tumor cell genome and possible variations in the relationship between nuclear genome and mitochondrial genetic determinants in tumor cell. For this purpose in mice C3HA tumors of hepatocellular origin were induced with N-nitroso-N-diethylamine, tissues of one of which were subjected to successive isologous transplantation during the period over 3 years. Normal hepatic tissues were taken for the control. As a result of a series of independent experiments (actinomycin D spectrophotometric titration, acridine orange binding, template activity, nuclear RNA/DNA hybridization) the results were obtained indicating a decrease in the amount of active loci in tumor hepatocytes genome. Hybridization data also indicate that in the tumor the derepression of chromosomal genes responsible for the genetic control over mitochondria and a non-regulated de-repression of mitochondrial genetic determinants take place."} {"id": "PMID:174309", "title": "[The work capacity and working arrangements of patients following stomach resection for cancer].", "content": "In 282 patients, subjected to gastric resection for cancer, the working capacity was examined according to the data of the Medical Expertise within different terms after surgery. It was found that most of patients in primary examination were acknowledged as disabled workers of the first and second group (70.1%). A dynamic follow-up of patients in late postoperative periods revealed a tendency toward an improvement of their working capacity in a group of patients previously considered as totally disabled. However, in terms over 5 years following the operation more than half of patients proved to be disabled. A comparative estimation of the working capacity in these patients according to the Medical Expertise and personal authors' data has revealed a discrepancy between the group of disability and the work accomplished, i.e. a considerable number of patients, considered as group II, resumed their former activities (as prior to surgery) or did easier jobs. This discrepancy seems, to a certain extent, to be the result of underestimation of the patients' state by the Medical Expertise Commission and overrating the group of disability in them.", "contents": "[The work capacity and working arrangements of patients following stomach resection for cancer]. In 282 patients, subjected to gastric resection for cancer, the working capacity was examined according to the data of the Medical Expertise within different terms after surgery. It was found that most of patients in primary examination were acknowledged as disabled workers of the first and second group (70.1%). A dynamic follow-up of patients in late postoperative periods revealed a tendency toward an improvement of their working capacity in a group of patients previously considered as totally disabled. However, in terms over 5 years following the operation more than half of patients proved to be disabled. A comparative estimation of the working capacity in these patients according to the Medical Expertise and personal authors' data has revealed a discrepancy between the group of disability and the work accomplished, i.e. a considerable number of patients, considered as group II, resumed their former activities (as prior to surgery) or did easier jobs. This discrepancy seems, to a certain extent, to be the result of underestimation of the patients' state by the Medical Expertise Commission and overrating the group of disability in them."} {"id": "PMID:174312", "title": "[Differences in the buoyant density of mitochondria from hepatoma, Krebs ascitic tumor II and normal liver].", "content": "Mitochondria isolated from normal liver, experimental hepatoma, and Krebs II ascites tumor tissues in mice were examined by isopycnic centrifugation in a sucrose density gradient (25--50%). Normal liver mitochondria were shown to be characterized by two visible zones, while those of tumors were distributed homogeneously. Such a distribution pattern was also confirmed by the investigation of marker enzyme activities (glucose-6-phosphatase and cytochromoxidase). A comparison of homologous tissues (hepatoma--liver) has evidenced that hepatoma mitochondria are \"lighter\" even than the \"light\" fraction of normal ones, that seems to evidence the disturbances in the biogenesis of these organelles. The results obtained are in a good agreement with the data reported by S. A. Neifakh on alterations in the structure of tumor mitochondrial membranes.", "contents": "[Differences in the buoyant density of mitochondria from hepatoma, Krebs ascitic tumor II and normal liver]. Mitochondria isolated from normal liver, experimental hepatoma, and Krebs II ascites tumor tissues in mice were examined by isopycnic centrifugation in a sucrose density gradient (25--50%). Normal liver mitochondria were shown to be characterized by two visible zones, while those of tumors were distributed homogeneously. Such a distribution pattern was also confirmed by the investigation of marker enzyme activities (glucose-6-phosphatase and cytochromoxidase). A comparison of homologous tissues (hepatoma--liver) has evidenced that hepatoma mitochondria are \"lighter\" even than the \"light\" fraction of normal ones, that seems to evidence the disturbances in the biogenesis of these organelles. The results obtained are in a good agreement with the data reported by S. A. Neifakh on alterations in the structure of tumor mitochondrial membranes."} {"id": "PMID:174313", "title": "[The damaging effect of the sodium salt of nystatin on ascitic tumor cells].", "content": "The experiments in vitro have demonstrated that an application of 0.1 mg/ml of nistatine into ascitic cells suspension would result in swelling of cells and 80% loss of intracellular potassium, associated with a considerable reduction of Na+K+-ATP-ase activity, the intensity of respiration and glycosis being changed but insignificantly. Thus, the influence of a polyene antibiotic - nistatine on the water-salt balance of ascitic cells under study is likely to be somewhat related with inhibition of NA+K+-dependent ATP-ase.", "contents": "[The damaging effect of the sodium salt of nystatin on ascitic tumor cells]. The experiments in vitro have demonstrated that an application of 0.1 mg/ml of nistatine into ascitic cells suspension would result in swelling of cells and 80% loss of intracellular potassium, associated with a considerable reduction of Na+K+-ATP-ase activity, the intensity of respiration and glycosis being changed but insignificantly. Thus, the influence of a polyene antibiotic - nistatine on the water-salt balance of ascitic cells under study is likely to be somewhat related with inhibition of NA+K+-dependent ATP-ase."} {"id": "PMID:174314", "title": "[Inhibition of the growth of spontaneous mammary gland tumors in mice by acetylated corticotropin].", "content": "As a result of chronic administration of acetylated corticotropin (anahormone), a decrease in the incidence of spontaneous mammary tumors in C3H/He mice has been noted. An administration of anahormone after a surgical removal of tumor either pre-or postoperatively) prolonged the free period in the development of recurrences and improved the survival rate of operated mice. It is presumed that inhibition of the tumor process by an anahormone is related with its suppressive action on the adrenal function and activity of the ovarian-gonadotropin system.", "contents": "[Inhibition of the growth of spontaneous mammary gland tumors in mice by acetylated corticotropin]. As a result of chronic administration of acetylated corticotropin (anahormone), a decrease in the incidence of spontaneous mammary tumors in C3H/He mice has been noted. An administration of anahormone after a surgical removal of tumor either pre-or postoperatively) prolonged the free period in the development of recurrences and improved the survival rate of operated mice. It is presumed that inhibition of the tumor process by an anahormone is related with its suppressive action on the adrenal function and activity of the ovarian-gonadotropin system."} {"id": "PMID:174315", "title": "[A change in the relative concentration of individual fractions of low molecular weight nuclear RNA in tumor tissues].", "content": "Low molecular weight nuclear RNAs (LMWN RNAs) of normal and neoplastic tissues: the rat liver and Zajdela hepatoma, mouse spleen and NK/Ly ascites tumor, as well as the cultures of normal chick embryo fibroblasts and of those transformed with Rous sarcoma virus were studied by electrophoresis in 8% and 15% polyacrylamide gels. As a result of the study no qualitative differences, i.e. differences in the number of LMWN RNA main fractions and their electrophoretic mobility were found. But there were revealed quantitative variations in the relative amount of definite fractions of these RNAs. An increase of the U3 RNA content in ascites tumors may be connected with an enhancement of the ribosomal RNA synthesis. Variations in the content of low molecular weight RNAs in oncogenic virus transformed cells may reflect an excessive synthesis of low molecular weight viral RNAs during the process of virus reproduction. The quantitative alterations observed seem to be of special value since LMWN RNAs are likely to perform regulatory functions.", "contents": "[A change in the relative concentration of individual fractions of low molecular weight nuclear RNA in tumor tissues]. Low molecular weight nuclear RNAs (LMWN RNAs) of normal and neoplastic tissues: the rat liver and Zajdela hepatoma, mouse spleen and NK/Ly ascites tumor, as well as the cultures of normal chick embryo fibroblasts and of those transformed with Rous sarcoma virus were studied by electrophoresis in 8% and 15% polyacrylamide gels. As a result of the study no qualitative differences, i.e. differences in the number of LMWN RNA main fractions and their electrophoretic mobility were found. But there were revealed quantitative variations in the relative amount of definite fractions of these RNAs. An increase of the U3 RNA content in ascites tumors may be connected with an enhancement of the ribosomal RNA synthesis. Variations in the content of low molecular weight RNAs in oncogenic virus transformed cells may reflect an excessive synthesis of low molecular weight viral RNAs during the process of virus reproduction. The quantitative alterations observed seem to be of special value since LMWN RNAs are likely to perform regulatory functions."} {"id": "PMID:174316", "title": "[Hypocholesteremic action of trepang (Stichopus japonicus) lipids].", "content": "The hypocholesteremic effect displated by the Japan Sea trepang is shown. The experiments were carried out on rabbits with hypocholesteremia caused by fasting. Total cholesterol, beta-lipoproteids, lipoid phosphorus, total phospholipids and the cholesterol/phospholipids ratio were determined in the blood of hypercholesteremic animals. The introduction of total trepang lipids to the hypercholesteremic fasting rabbits resulted in normalization of the lipids metabolism, this being indicative of the favourable effect produced by such lipids.", "contents": "[Hypocholesteremic action of trepang (Stichopus japonicus) lipids]. The hypocholesteremic effect displated by the Japan Sea trepang is shown. The experiments were carried out on rabbits with hypocholesteremia caused by fasting. Total cholesterol, beta-lipoproteids, lipoid phosphorus, total phospholipids and the cholesterol/phospholipids ratio were determined in the blood of hypercholesteremic animals. The introduction of total trepang lipids to the hypercholesteremic fasting rabbits resulted in normalization of the lipids metabolism, this being indicative of the favourable effect produced by such lipids."} {"id": "PMID:174317", "title": "[Redox state of the hepatic cells in rats kept on a diet containing 1,2-propanediol].", "content": "A comparative characterization of the redox condition and phosphate potential of the hepatic cells in rats kept on two experimental diets (low- and high-carbohydrate) is given. Intensification of the glucogenesis in the liver of rats kept on a low-carbohydrate diet is determined by lower values of the ratios /NAD+/: (NADH/ and /ATP/:/ADP/P1, the cells acquiring more marked reducting properties. Incorporation of 1,2-propanediol, as a source of metabolized energy, in the composition of the low-carbohydrate diet (20 per cent of the fat content) produces a rise in the level of glycogen and a fall of the liver lipids. The reducing capacity of the cytoplasma diminishes, this being borne out by the ratio of /NAD+/:/NADH/. An increase of the phosphate potential and of the ratio /NAD+/:/NADH/ is in these conditions similar to the one observed with a greater amount of carbohydrates in the diet. The phosphoenol-pyruvate-carboxykinase activity and concentration of malate in the liver diminish with rising concentration of oxaloacetate. When superimposed upon a high-carbohydrate diet 1,2-propanediol causes an increase of the /NAD+/:/NADH/ and /ATP/:P1/ ratios with the lipids content in the liver mounting too. The significance of shifts in the redox state and of the phosphate potential in regulating the 1,2-propanediol metabolism is discussed.", "contents": "[Redox state of the hepatic cells in rats kept on a diet containing 1,2-propanediol]. A comparative characterization of the redox condition and phosphate potential of the hepatic cells in rats kept on two experimental diets (low- and high-carbohydrate) is given. Intensification of the glucogenesis in the liver of rats kept on a low-carbohydrate diet is determined by lower values of the ratios /NAD+/: (NADH/ and /ATP/:/ADP/P1, the cells acquiring more marked reducting properties. Incorporation of 1,2-propanediol, as a source of metabolized energy, in the composition of the low-carbohydrate diet (20 per cent of the fat content) produces a rise in the level of glycogen and a fall of the liver lipids. The reducing capacity of the cytoplasma diminishes, this being borne out by the ratio of /NAD+/:/NADH/. An increase of the phosphate potential and of the ratio /NAD+/:/NADH/ is in these conditions similar to the one observed with a greater amount of carbohydrates in the diet. The phosphoenol-pyruvate-carboxykinase activity and concentration of malate in the liver diminish with rising concentration of oxaloacetate. When superimposed upon a high-carbohydrate diet 1,2-propanediol causes an increase of the /NAD+/:/NADH/ and /ATP/:P1/ ratios with the lipids content in the liver mounting too. The significance of shifts in the redox state and of the phosphate potential in regulating the 1,2-propanediol metabolism is discussed."} {"id": "PMID:174318", "title": "[The effect of egg white on the phospholipid level in blood plasma, erythrocytes and beta-lipoproteins of healthy children].", "content": "A single taking by children of eggs' white in an amount of 2 g/kg of the body weight resulted in that the blood plasma experienced a decline in the relative content of phosphatidylserine, lecithin and a rise in the level of phosphatidylethanolamine. In the membranes of erythrocytes there occurred a rise in the proportion of phosphatidylserine, phosphatidylethanolamine and a fall of the share of lecithin and sphyngomyelin. In the composition of beta-lipoproteins the level of phosphatidylethanolamine was up with a marked drop of phosphatidylserine. Variations in the content of sphyngomyelin and lecithin showed no characteristic features.", "contents": "[The effect of egg white on the phospholipid level in blood plasma, erythrocytes and beta-lipoproteins of healthy children]. A single taking by children of eggs' white in an amount of 2 g/kg of the body weight resulted in that the blood plasma experienced a decline in the relative content of phosphatidylserine, lecithin and a rise in the level of phosphatidylethanolamine. In the membranes of erythrocytes there occurred a rise in the proportion of phosphatidylserine, phosphatidylethanolamine and a fall of the share of lecithin and sphyngomyelin. In the composition of beta-lipoproteins the level of phosphatidylethanolamine was up with a marked drop of phosphatidylserine. Variations in the content of sphyngomyelin and lecithin showed no characteristic features."} {"id": "PMID:174319", "title": "A method of isolating enteroviruses from meat.", "content": "A method of isolating the virus ECHO II in specimens of stewed beef and cutlets is assessed. The procedure involves obtaining extracts of the meat with the saline (in ratios of 1:2 and 1:4) in combination with processing with freon 113. This method failed to detect in the meat samples analyzed 20-30 CPD50 of the virus in 1 g. Experiments demonstrated that eluation of the poliovirus from the meat into an aqueous saline depended on the proportion of meat and the eluating solution. It was shown that the optimal extraction of the poliovirus from meat into the solution was seen to occur with the proportions of meat and the eluating solution of 1:8-1:9.", "contents": "A method of isolating enteroviruses from meat. A method of isolating the virus ECHO II in specimens of stewed beef and cutlets is assessed. The procedure involves obtaining extracts of the meat with the saline (in ratios of 1:2 and 1:4) in combination with processing with freon 113. This method failed to detect in the meat samples analyzed 20-30 CPD50 of the virus in 1 g. Experiments demonstrated that eluation of the poliovirus from the meat into an aqueous saline depended on the proportion of meat and the eluating solution. It was shown that the optimal extraction of the poliovirus from meat into the solution was seen to occur with the proportions of meat and the eluating solution of 1:8-1:9."} {"id": "PMID:174321", "title": "[Analysis of cultures infected by vaccinal strains of viruses for detecting in them the integrated genome of these viruses (author's transl)].", "content": "White mice of 10-12 g were immunized with one of the three virus vaccines (vaccines against poliomyelitis, measles, smallpox) at various intervals. Poliovirus type II and measles virus, Edmonston strain, were labeled in tissue culture with 3H-uridine (30/uCi/ml). Smallpox virus (rabbit strain) was labeled with 3H-thymidine (30/uCi per ml) also in tissue culture. After purification and concentration of labeled poliomyelitis and measles viruses, viral RNA was isolated by double extraction with phenol, and precipitation with alcohol to which a yeast RNA-carrier was added. Isolation of 3H-thymidine-labeled viral RNA from smallpox virus was carried out by the same method with the addition of SDS to the final concentration of 1%. From the brain and lung cells of the vaccinated animals DNA was extracted by the kinetic reassociation method and hybridized with labeled viral nucleic acids. The formation of a hybrid with DNA-containing vaccine virus was controlled by chromatography in hydroxylapatite. No integration of viral and cell nucleic acids was demonstrated in our experiments, however, it cannot be ruled out completely, because this method does not detect homologous sequences if they occur in a small number of cells tested.", "contents": "[Analysis of cultures infected by vaccinal strains of viruses for detecting in them the integrated genome of these viruses (author's transl)]. White mice of 10-12 g were immunized with one of the three virus vaccines (vaccines against poliomyelitis, measles, smallpox) at various intervals. Poliovirus type II and measles virus, Edmonston strain, were labeled in tissue culture with 3H-uridine (30/uCi/ml). Smallpox virus (rabbit strain) was labeled with 3H-thymidine (30/uCi per ml) also in tissue culture. After purification and concentration of labeled poliomyelitis and measles viruses, viral RNA was isolated by double extraction with phenol, and precipitation with alcohol to which a yeast RNA-carrier was added. Isolation of 3H-thymidine-labeled viral RNA from smallpox virus was carried out by the same method with the addition of SDS to the final concentration of 1%. From the brain and lung cells of the vaccinated animals DNA was extracted by the kinetic reassociation method and hybridized with labeled viral nucleic acids. The formation of a hybrid with DNA-containing vaccine virus was controlled by chromatography in hydroxylapatite. No integration of viral and cell nucleic acids was demonstrated in our experiments, however, it cannot be ruled out completely, because this method does not detect homologous sequences if they occur in a small number of cells tested."} {"id": "PMID:174322", "title": "[Some physicochemical properties of the dysenteric therapeutic--prophylactic Newcastle phages H-17 and H-18 (Author's transl)].", "content": "Some physico-chemical properties of dysentery therapeutic-prophylactic Newcastle-phages H-17 and H-18 were studied. Both phages were shown to be resistant to sodium dodecyl sulphate at room temperature. Phage H-17 at room temperature was completely inactivated and phage H-18 inactivated by 40% by 1 M sodium hydrochloride. Phage H-18 was completely inactivated by 4 M sodium hydrochloride. Morphology and sizes of the phages are described. The buoyant density of phage H-17 was found to be 1.497 g/cm3, and of phage H-18 1.504 g/cm3. DNA of both phages were identified as double-stranded on the basis of the pattern of melting curve, of interaction with formaldehyde and absorption spectrum in solutions with various ionic strengths. The melting point of DNA of phage H-17 is 83.63 degrees C, phage H-18 89.67 degrees.", "contents": "[Some physicochemical properties of the dysenteric therapeutic--prophylactic Newcastle phages H-17 and H-18 (Author's transl)]. Some physico-chemical properties of dysentery therapeutic-prophylactic Newcastle-phages H-17 and H-18 were studied. Both phages were shown to be resistant to sodium dodecyl sulphate at room temperature. Phage H-17 at room temperature was completely inactivated and phage H-18 inactivated by 40% by 1 M sodium hydrochloride. Phage H-18 was completely inactivated by 4 M sodium hydrochloride. Morphology and sizes of the phages are described. The buoyant density of phage H-17 was found to be 1.497 g/cm3, and of phage H-18 1.504 g/cm3. DNA of both phages were identified as double-stranded on the basis of the pattern of melting curve, of interaction with formaldehyde and absorption spectrum in solutions with various ionic strengths. The melting point of DNA of phage H-17 is 83.63 degrees C, phage H-18 89.67 degrees."} {"id": "PMID:174324", "title": "[Cryomethod of concentrating interferon (author's transl)].", "content": "The fact of non-simultaneous thawing of protein and water was used for concentration of interferon from pre-frozen preparations. As thawing proceeded, 5 sequential fractions equal in a volume were removed from preparations of human leucocyte, mouse macrophage and tissue chick interferons; the titers of their antiveral activity in the first fraction were 4--8-fold higher than the initial titer, and this activity decreased gradually to a titer which was 2-fold lower than the initial in the fifth fraction. The total amount of interferon units in all the fractions was 1.8--3.8-fold higher than in the initial preparation taken in a volume corresponding to the total volume of all the fractions. As addition of the Vth fraction to the Ist fraction reduced the titer of interferon in it to the initial level, it is suggested that in interferon preparations there is an inhibitor of its effect, \"anti-interferon\".", "contents": "[Cryomethod of concentrating interferon (author's transl)]. The fact of non-simultaneous thawing of protein and water was used for concentration of interferon from pre-frozen preparations. As thawing proceeded, 5 sequential fractions equal in a volume were removed from preparations of human leucocyte, mouse macrophage and tissue chick interferons; the titers of their antiveral activity in the first fraction were 4--8-fold higher than the initial titer, and this activity decreased gradually to a titer which was 2-fold lower than the initial in the fifth fraction. The total amount of interferon units in all the fractions was 1.8--3.8-fold higher than in the initial preparation taken in a volume corresponding to the total volume of all the fractions. As addition of the Vth fraction to the Ist fraction reduced the titer of interferon in it to the initial level, it is suggested that in interferon preparations there is an inhibitor of its effect, \"anti-interferon\"."} {"id": "PMID:174323", "title": "[Study of the organotropic and oncotropic properties of human type 16 adenovirus in the body of Syrian hamsters and mice (author's transl)].", "content": "Human adenovirus type 16 was studied in Syrian hamsters bearing SV40 virus induced transplantable tumour and in mice of Black line with Lewis cancer. Despite its tropism to the tumour tissue, the virus injected into the blood stream was first accumulated in the lung tissue and in organs of the reticuloendothelial system (the spleen and liver). When the tumour was in the lung tissue of mice, the virus content in it was much higher than in a similar tumour of subcutaneous localization.", "contents": "[Study of the organotropic and oncotropic properties of human type 16 adenovirus in the body of Syrian hamsters and mice (author's transl)]. Human adenovirus type 16 was studied in Syrian hamsters bearing SV40 virus induced transplantable tumour and in mice of Black line with Lewis cancer. Despite its tropism to the tumour tissue, the virus injected into the blood stream was first accumulated in the lung tissue and in organs of the reticuloendothelial system (the spleen and liver). When the tumour was in the lung tissue of mice, the virus content in it was much higher than in a similar tumour of subcutaneous localization."} {"id": "PMID:174325", "title": "[Study of organ cultures of human embryonic intestines infected with the human cytomegalovirus and the Japanese encephalitis virus].", "content": "Reproduction of human cytomegalovirus (CMV) and Japanese encephalitis virus (JE) was studied in organ cultures of human embryo intestine under conditions of mono- and combined infection. The titer of JE virus in monoinfection reached its maximum level (10(7) TCD50/ml) whereas the titer of CMV did not exceed 10(2) TCD50/ml. In combined infection the titer of CMV increased to 10(5.5) TCD50/ml and the titer of JE virus remained at the same level (10(7) TCD50/ml). The results obtained in light and scanning electron microscopy studies indicate that in monoinfection CMV causes considerably earlier and more profound degenerative changes in mesanchymal elements of embryonal intestinal tissues than does JE virus. At the same time the combined infection of organ cultures with these viruses is not cytocidal.", "contents": "[Study of organ cultures of human embryonic intestines infected with the human cytomegalovirus and the Japanese encephalitis virus]. Reproduction of human cytomegalovirus (CMV) and Japanese encephalitis virus (JE) was studied in organ cultures of human embryo intestine under conditions of mono- and combined infection. The titer of JE virus in monoinfection reached its maximum level (10(7) TCD50/ml) whereas the titer of CMV did not exceed 10(2) TCD50/ml. In combined infection the titer of CMV increased to 10(5.5) TCD50/ml and the titer of JE virus remained at the same level (10(7) TCD50/ml). The results obtained in light and scanning electron microscopy studies indicate that in monoinfection CMV causes considerably earlier and more profound degenerative changes in mesanchymal elements of embryonal intestinal tissues than does JE virus. At the same time the combined infection of organ cultures with these viruses is not cytocidal."} {"id": "PMID:174331", "title": "[Hemihypertrophy].", "content": "Together with a casuistic description of a hemihypertrophy partialis cruciata vera congenita of a 20-year-old male patient a survey of literature is given concerning the problem of the hemihypertrophy.", "contents": "[Hemihypertrophy]. Together with a casuistic description of a hemihypertrophy partialis cruciata vera congenita of a 20-year-old male patient a survey of literature is given concerning the problem of the hemihypertrophy."} {"id": "PMID:174326", "title": "[Human rhinov\u00edruses circulating in Moscow (author's transl)].", "content": "In the period of 1971--1973 in Moscow, 85 strains of rhinoviruses (types IB, 14, 20, 27, 33, 48, 56, 60 and 69) were isolated from patients with respiratory diseases. In March-May 1971 in one administrative district of Moscow, from ambulatory patients with ARD rhinoviruses of types 48 (24 strains) and 27 (8 strains) were predominantly isolated. An outbreak of diseases due to these two types appeared to have occurred. From children rhinoviruses were isolated not only from nasopharyngeal washings. From 3 children they were isolated from the lower respiratory tract (from the blood collected before his death due to staphylococcal sepsis. Surveys for virus-neutralizing antibody to 17 rhinovirus serotypes in 10 lots of gamma globulin prepared in different towns of the Soviet Union revealed wide spread of rhinovirus types IB, 13, 18, 31 and 32 limited spread of types 17 and 42 and moderate spread of types 2, 3, 7, 10, 14, 21, 22, 24, 48 and 53.", "contents": "[Human rhinov\u00edruses circulating in Moscow (author's transl)]. In the period of 1971--1973 in Moscow, 85 strains of rhinoviruses (types IB, 14, 20, 27, 33, 48, 56, 60 and 69) were isolated from patients with respiratory diseases. In March-May 1971 in one administrative district of Moscow, from ambulatory patients with ARD rhinoviruses of types 48 (24 strains) and 27 (8 strains) were predominantly isolated. An outbreak of diseases due to these two types appeared to have occurred. From children rhinoviruses were isolated not only from nasopharyngeal washings. From 3 children they were isolated from the lower respiratory tract (from the blood collected before his death due to staphylococcal sepsis. Surveys for virus-neutralizing antibody to 17 rhinovirus serotypes in 10 lots of gamma globulin prepared in different towns of the Soviet Union revealed wide spread of rhinovirus types IB, 13, 18, 31 and 32 limited spread of types 17 and 42 and moderate spread of types 2, 3, 7, 10, 14, 21, 22, 24, 48 and 53."} {"id": "PMID:174327", "title": "[Cytological characteristics of a bovine kidney cell culture chronically infected with foot-and-mouth disease virus (author's transl)].", "content": "A virus-carrier state was observed in the process of subcultivation of foot-and-mouth disease virus-infected calf kidney cell culture. Cytologically, the chronically infected culture differed from the control culture by the presence of a large number of syncytial cells which did not die in acute infection because of poor susceptibility to the virus. Chronic infection appeared to be maintained by occasionaly polygonal cells which retained the initial sesceptiblity to foot-and-mouth disease virus. The number of such cells did not exceed 1--4% and by the 9th passage they disappeared completely. At this time the experimental culture did not differ from control cytologically and cytochemically.", "contents": "[Cytological characteristics of a bovine kidney cell culture chronically infected with foot-and-mouth disease virus (author's transl)]. A virus-carrier state was observed in the process of subcultivation of foot-and-mouth disease virus-infected calf kidney cell culture. Cytologically, the chronically infected culture differed from the control culture by the presence of a large number of syncytial cells which did not die in acute infection because of poor susceptibility to the virus. Chronic infection appeared to be maintained by occasionaly polygonal cells which retained the initial sesceptiblity to foot-and-mouth disease virus. The number of such cells did not exceed 1--4% and by the 9th passage they disappeared completely. At this time the experimental culture did not differ from control cytologically and cytochemically."} {"id": "PMID:174340", "title": "[Comparative light and electron microscopic study on liver cell inclusions in chronic alcoholic liver damage (author's transl)].", "content": "Liver cell inclusions in chronic alcoholic liver damage observed by means of the ligth microscope proved by correlated electron microscopy to be bile depositions, autophagic vacuoles, megamitochondria, alcoholic hyalin or accumulation of ribosomes. These liver cell inclusions are usually identifiable at the light microscopical level. The bile depositions undergo a lysosomal degradation. Thereby, they are converted into a pale brownish pigment and lose the property of reacting with histochemical bile tests. Owing to this brownish pigmentation bile depositions are distinguishable from the other mentioned liver cell inclusions under the light microscope. Autophagic vacuoles appear as eosinophilic inclusions and are PAS positive before as well as after the diastase treatment. On the contrary to these, the likewise eosinophilic megamitochondria are PAS negative, in the same way as alcoholic hyaline. With the procedure according to Goldner megamitochondria mostly strain red, whereas alcoholic hyalin lacks this property. Moreover, alcoholic hyalin is usually distinguishable from megamitochondria by its shape. Accumulations of ribosomes represent basophilic cytoplasm areas in light microscopy and are frequently located in he pericanalicular regions of liver epithelium.", "contents": "[Comparative light and electron microscopic study on liver cell inclusions in chronic alcoholic liver damage (author's transl)]. Liver cell inclusions in chronic alcoholic liver damage observed by means of the ligth microscope proved by correlated electron microscopy to be bile depositions, autophagic vacuoles, megamitochondria, alcoholic hyalin or accumulation of ribosomes. These liver cell inclusions are usually identifiable at the light microscopical level. The bile depositions undergo a lysosomal degradation. Thereby, they are converted into a pale brownish pigment and lose the property of reacting with histochemical bile tests. Owing to this brownish pigmentation bile depositions are distinguishable from the other mentioned liver cell inclusions under the light microscope. Autophagic vacuoles appear as eosinophilic inclusions and are PAS positive before as well as after the diastase treatment. On the contrary to these, the likewise eosinophilic megamitochondria are PAS negative, in the same way as alcoholic hyaline. With the procedure according to Goldner megamitochondria mostly strain red, whereas alcoholic hyalin lacks this property. Moreover, alcoholic hyalin is usually distinguishable from megamitochondria by its shape. Accumulations of ribosomes represent basophilic cytoplasm areas in light microscopy and are frequently located in he pericanalicular regions of liver epithelium."} {"id": "PMID:174344", "title": "[Comparative characteristics of the ultrastructure of the causative agents of glanders and melioidosis].", "content": "The authors examined the ultrastructure of the causative agents of glanders and melio idosis. It was revealed that the structure of their cell wall and of the cytoplasmic membrane was characteristic of Gram negative bacteria. The cytoplasm of both types of the causative agents showed the presence of ribosomes, membrane structure, nucleoid, and also osmiophilic and osmiophobic inclusions.", "contents": "[Comparative characteristics of the ultrastructure of the causative agents of glanders and melioidosis]. The authors examined the ultrastructure of the causative agents of glanders and melio idosis. It was revealed that the structure of their cell wall and of the cytoplasmic membrane was characteristic of Gram negative bacteria. The cytoplasm of both types of the causative agents showed the presence of ribosomes, membrane structure, nucleoid, and also osmiophilic and osmiophobic inclusions."} {"id": "PMID:174345", "title": "[The pathogenesis of the convulsion syndrome in children].", "content": "The report contains some results of clinical, biochemical and EEG studies convened in 24 children with convulsive attacks and in 34 children with organic lesions of the CNS and epileptiform syndromes. The authors point out to the important role of the diencephalic area in the pathogenesis of convulsive syndromes. Changes in the glucocortical functions of the adrenal system during the period of convulsive attacks are related to a disturbed regulation in the hypothalamo-hypophysar structure. The processes of readaptation are more disturbed in patients with organic lesions of the CNS in frequent attacks. The results of such studies speak of certain indications to hormone therapy in repeated convulsions in children, especially if the convulsions have an epileptiform character and occur in patients with organic lesions of the CNS.", "contents": "[The pathogenesis of the convulsion syndrome in children]. The report contains some results of clinical, biochemical and EEG studies convened in 24 children with convulsive attacks and in 34 children with organic lesions of the CNS and epileptiform syndromes. The authors point out to the important role of the diencephalic area in the pathogenesis of convulsive syndromes. Changes in the glucocortical functions of the adrenal system during the period of convulsive attacks are related to a disturbed regulation in the hypothalamo-hypophysar structure. The processes of readaptation are more disturbed in patients with organic lesions of the CNS in frequent attacks. The results of such studies speak of certain indications to hormone therapy in repeated convulsions in children, especially if the convulsions have an epileptiform character and occur in patients with organic lesions of the CNS."} {"id": "PMID:174346", "title": "[Disruption of motor habits in tumors of the premotor zone of the frontal lobe].", "content": "The report is concerned with the character of disordered complex automated movements in a group of patients with frontal lobe tumors. These disorders were studied with the aid of a neuropsychological technique elaborated by prof. Luria. A crude disautomation of voluntary movements appeared in cases of tumors of the supra-convexital area of the premotor zone. In lesions of the deep area of posterior frontal area with an involvement into the process of the subcortical structures an inertness in the motor sphere was registered.", "contents": "[Disruption of motor habits in tumors of the premotor zone of the frontal lobe]. The report is concerned with the character of disordered complex automated movements in a group of patients with frontal lobe tumors. These disorders were studied with the aid of a neuropsychological technique elaborated by prof. Luria. A crude disautomation of voluntary movements appeared in cases of tumors of the supra-convexital area of the premotor zone. In lesions of the deep area of posterior frontal area with an involvement into the process of the subcortical structures an inertness in the motor sphere was registered."} {"id": "PMID:174343", "title": "[Ultrastructure of the neurohypophysis in the lamprey, Lampetra fluviatilis L].", "content": "Three distinct zones are observed in the neurohypophysis (Nh) of adult lampreys: ependymal (tanycyte), fiber and neurovascular. The ependymal zone consists of a single layer of tanycyte perikarya. Their basal processes pass via the fiber zone and form vascular \"endfeet\" on the connective tissue layer, separating Nh and the meta-adenohypophysis. Few funnel-shaped protrusions of the recessus infundibuli lined with tanycytes penetrates deeply in Nh. Pituicytes are rare. Peptidergic A1 and A2 fibers and their terminals contain granules of 1600-3400 and 1200-2200 A in diameter respectively. Monoaminergic B type fibers have granules of 800-1000 A in diameter. Percentage of the A1 fibers is the lowest. Nerve terminals and tanycyte vascular \"endfeet\" make contact with the unusually thick (up to 3000 A) outer basement membrane. The latter is about 1 mu thick in sites where in invaginates deeply in Nh. Single short fragments of the inner basement membrane are seen. Sometimes peptidergic A1 and A2 nerve terminals are separated from the third ventricle or its protrusions only by a thin layer of tanycyte cytoplasm. Peptide neurohormones are probably released in the cerebro-spinal fluid in these sites. The possibility of peptide neurohormone and monoamine be discharged into the common circulation and their diffusion through the the connective tissue layer into the meta-adenohypophysis is discussed.", "contents": "[Ultrastructure of the neurohypophysis in the lamprey, Lampetra fluviatilis L]. Three distinct zones are observed in the neurohypophysis (Nh) of adult lampreys: ependymal (tanycyte), fiber and neurovascular. The ependymal zone consists of a single layer of tanycyte perikarya. Their basal processes pass via the fiber zone and form vascular \"endfeet\" on the connective tissue layer, separating Nh and the meta-adenohypophysis. Few funnel-shaped protrusions of the recessus infundibuli lined with tanycytes penetrates deeply in Nh. Pituicytes are rare. Peptidergic A1 and A2 fibers and their terminals contain granules of 1600-3400 and 1200-2200 A in diameter respectively. Monoaminergic B type fibers have granules of 800-1000 A in diameter. Percentage of the A1 fibers is the lowest. Nerve terminals and tanycyte vascular \"endfeet\" make contact with the unusually thick (up to 3000 A) outer basement membrane. The latter is about 1 mu thick in sites where in invaginates deeply in Nh. Single short fragments of the inner basement membrane are seen. Sometimes peptidergic A1 and A2 nerve terminals are separated from the third ventricle or its protrusions only by a thin layer of tanycyte cytoplasm. Peptide neurohormones are probably released in the cerebro-spinal fluid in these sites. The possibility of peptide neurohormone and monoamine be discharged into the common circulation and their diffusion through the the connective tissue layer into the meta-adenohypophysis is discussed."} {"id": "PMID:174347", "title": "[An x-ray and histologic study of calcifications of tumors of the subcortical ganglia of the brain].", "content": "X-ray and histological studies of 138 patients with tumors of subcortical nodes displayed signs of hypertension in 86.3% of the cases (119 cases). Calcified foci on the craniograms were found in 29 cases (21%) and in histological findings - in 48 cases (34.6%). Petrified foci in benign glial tumors were located between the tumor cells, perivascularly and in the tissue of the perifocal zone of the tumor. In malignant tumors the petrified foci were mainly in the area of necrosis, in microcysts and hemmorrhagical foci. According to the pattern of calcification on the x-ray it was impossible to determine the histological type of the tumor or the degree of malignancy. The volume of calcification on the craniograms do not correspond to the volume and configuration of the intracranial tumor.", "contents": "[An x-ray and histologic study of calcifications of tumors of the subcortical ganglia of the brain]. X-ray and histological studies of 138 patients with tumors of subcortical nodes displayed signs of hypertension in 86.3% of the cases (119 cases). Calcified foci on the craniograms were found in 29 cases (21%) and in histological findings - in 48 cases (34.6%). Petrified foci in benign glial tumors were located between the tumor cells, perivascularly and in the tissue of the perifocal zone of the tumor. In malignant tumors the petrified foci were mainly in the area of necrosis, in microcysts and hemmorrhagical foci. According to the pattern of calcification on the x-ray it was impossible to determine the histological type of the tumor or the degree of malignancy. The volume of calcification on the craniograms do not correspond to the volume and configuration of the intracranial tumor."} {"id": "PMID:174348", "title": "[Nervous system lesions in juvenile angiofibromas of the base of the skull with intracranial spread].", "content": "The authors examined the nervous system in 12 patients with intracranial dissemination of an adolescent angiofibroma of the brain basis. It was possible to depict signs of a lesion of some cranial nerves and the brain stem as well as x-ray confirmation of a bone destruction in the brain basis. The found changes were connected with the direct influence of the angiofibroma on the above mentioned structures.", "contents": "[Nervous system lesions in juvenile angiofibromas of the base of the skull with intracranial spread]. The authors examined the nervous system in 12 patients with intracranial dissemination of an adolescent angiofibroma of the brain basis. It was possible to depict signs of a lesion of some cranial nerves and the brain stem as well as x-ray confirmation of a bone destruction in the brain basis. The found changes were connected with the direct influence of the angiofibroma on the above mentioned structures."} {"id": "PMID:174349", "title": "[Irregularities in the lipid composition of muscle tissue in Duchenne's myodystrophy].", "content": "A study is made of the phospholipid content, glycerides and cholesterine in the muscular tissue of 20 patients with Duchene's myodystrophy. It was established that there is an increase in the relative content of sphingomyelin and a drop in phosphatidilcholine. The study shows an increase of glycerides and cholesterine per gm, of raw weight and in the content of the noncollagen protein.", "contents": "[Irregularities in the lipid composition of muscle tissue in Duchenne's myodystrophy]. A study is made of the phospholipid content, glycerides and cholesterine in the muscular tissue of 20 patients with Duchene's myodystrophy. It was established that there is an increase in the relative content of sphingomyelin and a drop in phosphatidilcholine. The study shows an increase of glycerides and cholesterine per gm, of raw weight and in the content of the noncollagen protein."} {"id": "PMID:174350", "title": "[Antimycin A-resistant oxygen consumption in rabbit reticulocytes].", "content": "In rabbit reticulocytes there exists an Antimycin A-resistent oxygen consumption. It amounts to about 20% of the total oxygen consumption, independently of the degree of maturation of the cells and of the presence of external substrates. The main substrate of the Antimycin A-resistent oxygen consumption is glucose, which is metabolized by the pentose phosphate pathway. NADP-dependent substrates provide more CO2 in the presence of Antimycin A. The 14CO2-formation from metabolites of the citric acid cycle and of metabolites directly connected with this cycle is decreased in the presence of Antimycin A, whereas no 14CO2 is formed from long-chain fatty acids. A H2O2-formation by a NADPH-oxygenase is postulated. The mitochondria contribute reducing equivalents to the cytosolic oxygen consumption. The postulated interactions include hydrogen transfer and the malate-shuttle.", "contents": "[Antimycin A-resistant oxygen consumption in rabbit reticulocytes]. In rabbit reticulocytes there exists an Antimycin A-resistent oxygen consumption. It amounts to about 20% of the total oxygen consumption, independently of the degree of maturation of the cells and of the presence of external substrates. The main substrate of the Antimycin A-resistent oxygen consumption is glucose, which is metabolized by the pentose phosphate pathway. NADP-dependent substrates provide more CO2 in the presence of Antimycin A. The 14CO2-formation from metabolites of the citric acid cycle and of metabolites directly connected with this cycle is decreased in the presence of Antimycin A, whereas no 14CO2 is formed from long-chain fatty acids. A H2O2-formation by a NADPH-oxygenase is postulated. The mitochondria contribute reducing equivalents to the cytosolic oxygen consumption. The postulated interactions include hydrogen transfer and the malate-shuttle."} {"id": "PMID:174359", "title": "The function of polymorphonuclear leukocytes after surgical trauma.", "content": "The effect of surgical trauma on human polymorphonuclear leukocytes (PMN) was studied by measuring the hexosemonophosphate shunt (HMS) activity and myeloperoxidase mediated iodination during phagocytosis. Patients submitted to elective general surgery showed normal iodination capacity and normal HMS activity in their PMN cells postoperatively. This implies that postoperative infectious complications are not caused or promoted by defective PMN cell function. Iodination was found significantly (p less than 0.05) impaired in phagocytosing PMN cells from burned patients whereas it was found normal in traumatic and septic conditions. No direct relation between extent of injury and degree of leukocyte impairment was found. HMS activity remained normal in burned patients suggesting that the impaired iodination might depend on a defective mobilization of lysosomal enzymes.", "contents": "The function of polymorphonuclear leukocytes after surgical trauma. The effect of surgical trauma on human polymorphonuclear leukocytes (PMN) was studied by measuring the hexosemonophosphate shunt (HMS) activity and myeloperoxidase mediated iodination during phagocytosis. Patients submitted to elective general surgery showed normal iodination capacity and normal HMS activity in their PMN cells postoperatively. This implies that postoperative infectious complications are not caused or promoted by defective PMN cell function. Iodination was found significantly (p less than 0.05) impaired in phagocytosing PMN cells from burned patients whereas it was found normal in traumatic and septic conditions. No direct relation between extent of injury and degree of leukocyte impairment was found. HMS activity remained normal in burned patients suggesting that the impaired iodination might depend on a defective mobilization of lysosomal enzymes."} {"id": "PMID:174360", "title": "Differences in action of LH and FSH on the formation of cyclic AMP in the prepubertal rat ovary.", "content": "The actions of LH (NIH-LH-B8) and FSH (NIH-FSH-S9) on the cyclic AMP (cAMP) system in ovaries of 23-24 day old rats have been analyzed. An intravenous injection of LH increased ovarian cAMP levels in vivo after only 20 seconds. Maximal cAMP levels were seen after 15 min. Addition of LH or FSH in vitro to the isolated ovaries produced dose dependent increases of cAMP in the tissue as well as in the incubation medium. Low concentrations of LH caused a release of cAMP into the incubation medium without any detectable change in the tissue levels. The levels of cAMP in the incubation media for all concentrations of FSH were lower than the tissue levels, whereas for LH the opposite was found. In time-course experiments where the concentrations of LH (10 mug/ml) and FSH (100 mug/ml) were chosen to give similar tissue levels of cAMP, the release of the cyclic nucleotide into the incubation medium was approximately 2-3 times greater for LH than for FSH at the time periods studied (5-240 min). When LH and FSH were tested together in high concentrations, their effects were additive. When the ovaries were first incubated with FSH for 120 min followed by an incubation with LH, the stimulatory effect of LH was considerably reduced. When the order of the incubations was reversed, however, LH did not change the response to FSH. The results show that both LH and FSH have intrinsic effects on the cAMP system in the prepubertal rat ovary, but that the effects of the two gonadotrophins are not identical.", "contents": "Differences in action of LH and FSH on the formation of cyclic AMP in the prepubertal rat ovary. The actions of LH (NIH-LH-B8) and FSH (NIH-FSH-S9) on the cyclic AMP (cAMP) system in ovaries of 23-24 day old rats have been analyzed. An intravenous injection of LH increased ovarian cAMP levels in vivo after only 20 seconds. Maximal cAMP levels were seen after 15 min. Addition of LH or FSH in vitro to the isolated ovaries produced dose dependent increases of cAMP in the tissue as well as in the incubation medium. Low concentrations of LH caused a release of cAMP into the incubation medium without any detectable change in the tissue levels. The levels of cAMP in the incubation media for all concentrations of FSH were lower than the tissue levels, whereas for LH the opposite was found. In time-course experiments where the concentrations of LH (10 mug/ml) and FSH (100 mug/ml) were chosen to give similar tissue levels of cAMP, the release of the cyclic nucleotide into the incubation medium was approximately 2-3 times greater for LH than for FSH at the time periods studied (5-240 min). When LH and FSH were tested together in high concentrations, their effects were additive. When the ovaries were first incubated with FSH for 120 min followed by an incubation with LH, the stimulatory effect of LH was considerably reduced. When the order of the incubations was reversed, however, LH did not change the response to FSH. The results show that both LH and FSH have intrinsic effects on the cAMP system in the prepubertal rat ovary, but that the effects of the two gonadotrophins are not identical."} {"id": "PMID:174361", "title": "A histochemical approach to the study of human chorionic gonadotrophin receptors in the rat testis.", "content": "Standard suspensions of interstitial cells in PBS were exposed to the action of various fixatives, solvents (clearing agents), temperatures and U. V. light, in order to establish the effects of such chemical and physical agents on the HCG receptors. After exposure to the various agents, the interstitial cells were incubated with [125I]HCG for 2 h at 37 degrees C. To check the specificity of the reaction, competitive tests were performed with added excess non-iodinated HCG. Only formaldehyde fixation for short periods of time, preserved satisfactorily the specific binding activity of the receptors. A different degree of thermolability of the receptors was demonstrated, in relation to 37, 45, 54 and 60 degrees C, while freezing in liquid nitrogen had no effect on the receptors binding activity. After the binding reaction, solvents had a significant solubilizing effect on the HCG-receptor complexes. U. V. light had no significant damaging effect on the receptors. The application of the results for a histochemical approach to the study of the HCG receptors is discussed.", "contents": "A histochemical approach to the study of human chorionic gonadotrophin receptors in the rat testis. Standard suspensions of interstitial cells in PBS were exposed to the action of various fixatives, solvents (clearing agents), temperatures and U. V. light, in order to establish the effects of such chemical and physical agents on the HCG receptors. After exposure to the various agents, the interstitial cells were incubated with [125I]HCG for 2 h at 37 degrees C. To check the specificity of the reaction, competitive tests were performed with added excess non-iodinated HCG. Only formaldehyde fixation for short periods of time, preserved satisfactorily the specific binding activity of the receptors. A different degree of thermolability of the receptors was demonstrated, in relation to 37, 45, 54 and 60 degrees C, while freezing in liquid nitrogen had no effect on the receptors binding activity. After the binding reaction, solvents had a significant solubilizing effect on the HCG-receptor complexes. U. V. light had no significant damaging effect on the receptors. The application of the results for a histochemical approach to the study of the HCG receptors is discussed."} {"id": "PMID:174362", "title": "Suppressive effect of L-dopa on human prolactin release during sleep.", "content": "Immunoreactive plasma human prolactin (HPr) and human growth hormone (HGH) concentrations were measured in six normal young men with polygraphic sleep monitoring during normal sleep and during sleep in which l-dihydroxyphenylalanine (l-DOPA) was infused intravenously at a rate of 0.8 to 1.0 mg/min. The intravenous infusion of l-DOPA significantly suppressed the episodic release of HPr during sleep and the occurrence of rapid eye movement (REM) sleep. However, HGH release during sleep was not remarkably influenced by l-DOPA. These results suggest that central catecholaminergic neural mechanisms are related to both sleep-related HPr release and REM sleep, but do not play an important role in sleep-related HGH release.", "contents": "Suppressive effect of L-dopa on human prolactin release during sleep. Immunoreactive plasma human prolactin (HPr) and human growth hormone (HGH) concentrations were measured in six normal young men with polygraphic sleep monitoring during normal sleep and during sleep in which l-dihydroxyphenylalanine (l-DOPA) was infused intravenously at a rate of 0.8 to 1.0 mg/min. The intravenous infusion of l-DOPA significantly suppressed the episodic release of HPr during sleep and the occurrence of rapid eye movement (REM) sleep. However, HGH release during sleep was not remarkably influenced by l-DOPA. These results suggest that central catecholaminergic neural mechanisms are related to both sleep-related HPr release and REM sleep, but do not play an important role in sleep-related HGH release."} {"id": "PMID:174364", "title": "A simple competitive protein-binding assay for adenosine-3',5'-monophosphate in plasma and urine.", "content": "A modified competitive protein-binding assay for the measurement of adenosine-3',5'-monophosphate is described. The procedure allows measurement of adenosine-3',5'-monophosphate in unextracted plasma samples. The mean plasma values in 25 normal, fasting and ambulatory subjects were 22.7 +/- 4.7 pmol/ml (mean +/- SD) (range 13-31 pmol/ml. The mean urinary content was 3.2 +/- 1.0 mumol per g creatinine (mean +/- SD) (n=24).", "contents": "A simple competitive protein-binding assay for adenosine-3',5'-monophosphate in plasma and urine. A modified competitive protein-binding assay for the measurement of adenosine-3',5'-monophosphate is described. The procedure allows measurement of adenosine-3',5'-monophosphate in unextracted plasma samples. The mean plasma values in 25 normal, fasting and ambulatory subjects were 22.7 +/- 4.7 pmol/ml (mean +/- SD) (range 13-31 pmol/ml. The mean urinary content was 3.2 +/- 1.0 mumol per g creatinine (mean +/- SD) (n=24)."} {"id": "PMID:174363", "title": "Hypothalamic-pituitary-testicular system and adrenocortical function.", "content": "Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.", "contents": "Hypothalamic-pituitary-testicular system and adrenocortical function. Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat."} {"id": "PMID:174365", "title": "Action of cyclic adenosine 3',5' monophosphate on L-14C-leucine incorporation in a system of rough microsomes from bovine thyroid gland.", "content": "The effect of cAMP and varying concentrations of potassium (18-72 mM) on the incorporation of L-14C-leucine into TCA-precipitable protein was studied in a cell-free system comprising rough thyroid microsomes. cAMP (2mM) alone or in combination with theopylline increased the incorporation of leucine into ribosome-bound (after DOC treatment) and extra-vesicular material, but had no significant effect on the DOC-released intravesicular material. Increase of the K+ concentration from 18 mM to 72 mM affected the incorporation of leucine into the microsomal compartments in much the same way as cAMP did. The effect of cAMP and potassium seems to be due in partly to enhanced activation of amino acids, since in a system of pH5 fraction and cell sap, both cAMP and K+ increased the incorporation of 14C-leucine into cold TCA-precipitable material. Experiments with 14C-leucyl-tRNA as a marker suggest that the effect of cAMP and K+ is a consequence not only of increased activation of amino acids, but also of increased binding of activated amino acyl-tRNA to ribosomes.", "contents": "Action of cyclic adenosine 3',5' monophosphate on L-14C-leucine incorporation in a system of rough microsomes from bovine thyroid gland. The effect of cAMP and varying concentrations of potassium (18-72 mM) on the incorporation of L-14C-leucine into TCA-precipitable protein was studied in a cell-free system comprising rough thyroid microsomes. cAMP (2mM) alone or in combination with theopylline increased the incorporation of leucine into ribosome-bound (after DOC treatment) and extra-vesicular material, but had no significant effect on the DOC-released intravesicular material. Increase of the K+ concentration from 18 mM to 72 mM affected the incorporation of leucine into the microsomal compartments in much the same way as cAMP did. The effect of cAMP and potassium seems to be due in partly to enhanced activation of amino acids, since in a system of pH5 fraction and cell sap, both cAMP and K+ increased the incorporation of 14C-leucine into cold TCA-precipitable material. Experiments with 14C-leucyl-tRNA as a marker suggest that the effect of cAMP and K+ is a consequence not only of increased activation of amino acids, but also of increased binding of activated amino acyl-tRNA to ribosomes."} {"id": "PMID:174366", "title": "The stimulation of growth hormone release by ACTH and its inhibition by somatostatin.", "content": "The rapid injection of 0.5 or 1.0 mg of tetracosacitid (Synacthen\u00bf) was followed by a distinct increase of plasma growth hormone (GH) within 30 or 45 min in 5 of 7 normal volunteers. A second control test was performed in 3 of the 5 \"responders\" and 1 \"non-responder\" and showed a consistent reaction in all of them. The tests were then repeated in the 5 \"responders\" during an infusion of somatostatin (150 mug/h) and the GH response was totally abolished (3 subjects) or markedly reduced (2 subjects). Thus the ACTH induced GH release behaves in a manner similar to most other physiological or pharmacological stimuli of GH release. The cortisol output after ACTH was not altered by somatostatin.", "contents": "The stimulation of growth hormone release by ACTH and its inhibition by somatostatin. The rapid injection of 0.5 or 1.0 mg of tetracosacitid (Synacthen\u00bf) was followed by a distinct increase of plasma growth hormone (GH) within 30 or 45 min in 5 of 7 normal volunteers. A second control test was performed in 3 of the 5 \"responders\" and 1 \"non-responder\" and showed a consistent reaction in all of them. The tests were then repeated in the 5 \"responders\" during an infusion of somatostatin (150 mug/h) and the GH response was totally abolished (3 subjects) or markedly reduced (2 subjects). Thus the ACTH induced GH release behaves in a manner similar to most other physiological or pharmacological stimuli of GH release. The cortisol output after ACTH was not altered by somatostatin."} {"id": "PMID:174367", "title": "The effect of ACTH on plasma testosterone and androstenedione concentrations in patients with prostatic carcinoma.", "content": "The effect of Synacthen (beta1-24-corticotrophin) on plasma testosterone and 4-androstene-3, 17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients. The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH.", "contents": "The effect of ACTH on plasma testosterone and androstenedione concentrations in patients with prostatic carcinoma. The effect of Synacthen (beta1-24-corticotrophin) on plasma testosterone and 4-androstene-3, 17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients. The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH."} {"id": "PMID:174368", "title": "Determination of plasma aldosterone in children by thin layer chromatography and radioimmunoassay.", "content": "An accurate and relatively simple radioimmunoassay for the determination of aldosterone concentration in peripheral plasma has been developed, 0.5-2.0 ml plasma with added [1,2-3H]aldosterone is extracted with dichloromethane. Purification of the extract is achieved by thin later chromatography in the system benzene-acetone 1:1. Recovery of [1,2-3H] aldosterone is 58 +/- 6 (SD)%. Bound and free fractions are separated by dextran-coated charcoal. The intra-assay reproducibility is 8.8% and the inter-assay reproducibility varies from 11.4-16.1%. The sensitivity of the assay for a 5 ml plasma sample can be put at 0.2 ng/100 ml. Normal values determined in 52 healthy children of different age groups are presented. Furthermore the aldosterone stimulating effect of low sodium diet (17 children), severe and prolonged vomiting (19 children) and synthetic ACTH (10 children) has been studied by our modified method.", "contents": "Determination of plasma aldosterone in children by thin layer chromatography and radioimmunoassay. An accurate and relatively simple radioimmunoassay for the determination of aldosterone concentration in peripheral plasma has been developed, 0.5-2.0 ml plasma with added [1,2-3H]aldosterone is extracted with dichloromethane. Purification of the extract is achieved by thin later chromatography in the system benzene-acetone 1:1. Recovery of [1,2-3H] aldosterone is 58 +/- 6 (SD)%. Bound and free fractions are separated by dextran-coated charcoal. The intra-assay reproducibility is 8.8% and the inter-assay reproducibility varies from 11.4-16.1%. The sensitivity of the assay for a 5 ml plasma sample can be put at 0.2 ng/100 ml. Normal values determined in 52 healthy children of different age groups are presented. Furthermore the aldosterone stimulating effect of low sodium diet (17 children), severe and prolonged vomiting (19 children) and synthetic ACTH (10 children) has been studied by our modified method."} {"id": "PMID:174369", "title": "Hepatitis B antigen in liver cirrhosis and hepatocellular carcinoma.", "content": "Postmortem diagnosis of liver cirrhosis was made over a one-year period in 43 cases, 18 of which also exhibited hepatocellular carcinoma. Blood samples taken from these and 120 other patients who died from other diseases were tested for hepatitis-B antigen (HB-Ag) and its antibodies (HB-AB) by counter-electrophoresis. The types of cirrhosis found were classified on the basis of morphological characteristics and available etiological data. The greater part of controls had had cardiovascular diseases and 32 had had non-hepatic carcinoma. Age limits were similar in the cirrhotic and control groups. HB-Ag was detected in 5 of the 25 subjects with macronodular cirrhosis and in one alcoholic patient among 18 subjects with other types of cirrhosis. The possibility of a coincidental HB virus infection existed in the alcoholic case and in one case of macronodular cirrhosis. Only one patient with liver carcinoma had HB-Ag. Among the 120 controls, HB-Ag and HB-AB were found in a one case. Microscopic lesions did not seem to be related specifically to the presence of HB-Ag in the cirrhotic livers.", "contents": "Hepatitis B antigen in liver cirrhosis and hepatocellular carcinoma. Postmortem diagnosis of liver cirrhosis was made over a one-year period in 43 cases, 18 of which also exhibited hepatocellular carcinoma. Blood samples taken from these and 120 other patients who died from other diseases were tested for hepatitis-B antigen (HB-Ag) and its antibodies (HB-AB) by counter-electrophoresis. The types of cirrhosis found were classified on the basis of morphological characteristics and available etiological data. The greater part of controls had had cardiovascular diseases and 32 had had non-hepatic carcinoma. Age limits were similar in the cirrhotic and control groups. HB-Ag was detected in 5 of the 25 subjects with macronodular cirrhosis and in one alcoholic patient among 18 subjects with other types of cirrhosis. The possibility of a coincidental HB virus infection existed in the alcoholic case and in one case of macronodular cirrhosis. Only one patient with liver carcinoma had HB-Ag. Among the 120 controls, HB-Ag and HB-AB were found in a one case. Microscopic lesions did not seem to be related specifically to the presence of HB-Ag in the cirrhotic livers."} {"id": "PMID:174370", "title": "Hepatic prolyl hydroxylase activity in experimental cirrhosis.", "content": "Hepatic collagen synthesis was studied during progressive fibrosis induced by carbon tetrachloride in male Sprague-Dawley rats by determination of prolyl hydroxylase activity and hydrocyproline levels along with morphological assessment of fibrosis. Cirrhosis was present after approximately 4 weeks treatment. Prolyl hydroxylase activity was increased significantly before fibrosis was apparent histologically or by hydroxyproline levels. The significance of this finding is discussed.", "contents": "Hepatic prolyl hydroxylase activity in experimental cirrhosis. Hepatic collagen synthesis was studied during progressive fibrosis induced by carbon tetrachloride in male Sprague-Dawley rats by determination of prolyl hydroxylase activity and hydrocyproline levels along with morphological assessment of fibrosis. Cirrhosis was present after approximately 4 weeks treatment. Prolyl hydroxylase activity was increased significantly before fibrosis was apparent histologically or by hydroxyproline levels. The significance of this finding is discussed."} {"id": "PMID:174371", "title": "Histochemical distribution of acid mucopolysaccharides in the cartilage of the selachians.", "content": "From an analysis of the histochemical data obtained in studies on the cartilage of the various pieces of the skeleton of Torpedo ocellata and Scylliorhinus canicula, it has been possible to deduce that the matrix contains a considerable quantity of nonsulfated acid mucopolysaccharides, chiefly relatable to the hyaluronic acid, and sulfated mucopolysaccharides relatable to the chondroitinsulfates A and C. The capsules show a prevalence of chondroitinsulfates. The presence of the latter substances is discussed, together with the probable mechanical function that they perform.", "contents": "Histochemical distribution of acid mucopolysaccharides in the cartilage of the selachians. From an analysis of the histochemical data obtained in studies on the cartilage of the various pieces of the skeleton of Torpedo ocellata and Scylliorhinus canicula, it has been possible to deduce that the matrix contains a considerable quantity of nonsulfated acid mucopolysaccharides, chiefly relatable to the hyaluronic acid, and sulfated mucopolysaccharides relatable to the chondroitinsulfates A and C. The capsules show a prevalence of chondroitinsulfates. The presence of the latter substances is discussed, together with the probable mechanical function that they perform."} {"id": "PMID:174373", "title": "Effect of dose of estradiol and age of animals on intranuclear inclusions in mammotrophs of the Mongolian gerbil.", "content": "Intranuclear inclusions have been examined in mammotrophs of the Mongolian gerbil. No inclusions were identified in nuclei of newborn females, although inclusions were seen in the pituitary gland of young mature females. The number of inclusions in retired breeders was similar to that in young females. Estradiol benzoate increased the number of inclusions, although 10 mug/day for 5 or 14 days induced more inclusions than 5 or 100 mug for 14 days; significantly fewer inclusions were seen with the higher dose (2.81 +/- 0.10 inclusions per field for 10 mug and 2.19 +/- 0.01 inclusions for 100 mug). Significantly fewer inclusions were present at 3 and 4 weeks. The reduced number of inclusions may be attributable at least in part to cellular hypertrophy of mammotrophs which was especially prominent. Vacuolar inclusions predominated at 3 and 4 weeks and there were fewer membranous types than at previous times.", "contents": "Effect of dose of estradiol and age of animals on intranuclear inclusions in mammotrophs of the Mongolian gerbil. Intranuclear inclusions have been examined in mammotrophs of the Mongolian gerbil. No inclusions were identified in nuclei of newborn females, although inclusions were seen in the pituitary gland of young mature females. The number of inclusions in retired breeders was similar to that in young females. Estradiol benzoate increased the number of inclusions, although 10 mug/day for 5 or 14 days induced more inclusions than 5 or 100 mug for 14 days; significantly fewer inclusions were seen with the higher dose (2.81 +/- 0.10 inclusions per field for 10 mug and 2.19 +/- 0.01 inclusions for 100 mug). Significantly fewer inclusions were present at 3 and 4 weeks. The reduced number of inclusions may be attributable at least in part to cellular hypertrophy of mammotrophs which was especially prominent. Vacuolar inclusions predominated at 3 and 4 weeks and there were fewer membranous types than at previous times."} {"id": "PMID:174374", "title": "Histochemical observations on the juxtanuclear complex of organelles in the hamster oocyte.", "content": "The hamster ovarian oocyte surrounded by 2-3 layers of granulosa cells develops a large juxtanuclear complex of organelles, consisting of basophilic substance, mitochondria and some lipid inclusion bodies. The basophilic substance staining for RNA, protein and some diffuse lipoprotein forms the material with which the granular mitochondria, composed of protein and phospholipid, apparently multiply. The lipid inclusion bodies consist of phospholipids. The results of this histochemical investigation have been correlated with those of ultrastructural studies on the hamster oocyte. The paranuclear complex of organelles described in this paper has also been compared and contrasted with that seen in the primordial oocyte of hamster, as reported in the previous publication. The functional significance of juxtanuclear entities has been discussed in relation to the multiplication of organelles to be accumulated during oocyte growth.", "contents": "Histochemical observations on the juxtanuclear complex of organelles in the hamster oocyte. The hamster ovarian oocyte surrounded by 2-3 layers of granulosa cells develops a large juxtanuclear complex of organelles, consisting of basophilic substance, mitochondria and some lipid inclusion bodies. The basophilic substance staining for RNA, protein and some diffuse lipoprotein forms the material with which the granular mitochondria, composed of protein and phospholipid, apparently multiply. The lipid inclusion bodies consist of phospholipids. The results of this histochemical investigation have been correlated with those of ultrastructural studies on the hamster oocyte. The paranuclear complex of organelles described in this paper has also been compared and contrasted with that seen in the primordial oocyte of hamster, as reported in the previous publication. The functional significance of juxtanuclear entities has been discussed in relation to the multiplication of organelles to be accumulated during oocyte growth."} {"id": "PMID:174375", "title": "Cytochrome oxidase and ascorbic acid in the normal and regenerating tail of the scincid lizard, Mabuya carinata. A histophysiological study.", "content": "The concentration of ascorbic acid (AA) and the histochemical distribution of this vitamin together with cytochrome oxidase have been investigated in the normal and regenerating tail of the Scincid lizard, Mabuya carinata. An interesting aspect of this investigation is the observation of a total lack of cytochrome oxidase in both the normal and regenerating tail of the lizard, except for the differentiating phase. On the other hand, AA has been found to be present in the normal and regenerating tail with above normal levels during wound healing (twofold) and differentiation (fivefold). In the light of the poor cytochrome oxidase activity, the higher content of AA noted during regeneration has been construed to play a possible role in the respiratory mechanics of the regenerating lizard tail. Further, the importance of AA in cellular metabolism and the wound healing and differentiative processes have also been discussed.", "contents": "Cytochrome oxidase and ascorbic acid in the normal and regenerating tail of the scincid lizard, Mabuya carinata. A histophysiological study. The concentration of ascorbic acid (AA) and the histochemical distribution of this vitamin together with cytochrome oxidase have been investigated in the normal and regenerating tail of the Scincid lizard, Mabuya carinata. An interesting aspect of this investigation is the observation of a total lack of cytochrome oxidase in both the normal and regenerating tail of the lizard, except for the differentiating phase. On the other hand, AA has been found to be present in the normal and regenerating tail with above normal levels during wound healing (twofold) and differentiation (fivefold). In the light of the poor cytochrome oxidase activity, the higher content of AA noted during regeneration has been construed to play a possible role in the respiratory mechanics of the regenerating lizard tail. Further, the importance of AA in cellular metabolism and the wound healing and differentiative processes have also been discussed."} {"id": "PMID:174376", "title": "Electron spin resonance spectra of chicken hepatoma and liver tissue.", "content": "When studied by electron spin resonance (ESR) (Swartz et al., 1972), tumorous tissues differ from their normal equivalents in the following aspects: 1. In tumourous tissues the signal measured in the vicinity of the g=2 region of the spectrum is of a smaller amplitude or completely absent (Commoner et al., 1954; Commoner, Ternberg, 1961; Mallard, Kent, 1964; Dodd, 1973). 2. Signals attributed to certain paramagnetic metal ions are also decreased (Nebert and Mason, 1963; Swartz et al., 1973). New lines may exceptionally appear, too (Mallard, Kent, 1966). So far mostly human and mammalian tumours (hepatoma and liver tissue) induced by carcinogens have been studied. The aim of the present work was to extend these observations to a fowl tumour of viral origin.", "contents": "Electron spin resonance spectra of chicken hepatoma and liver tissue. When studied by electron spin resonance (ESR) (Swartz et al., 1972), tumorous tissues differ from their normal equivalents in the following aspects: 1. In tumourous tissues the signal measured in the vicinity of the g=2 region of the spectrum is of a smaller amplitude or completely absent (Commoner et al., 1954; Commoner, Ternberg, 1961; Mallard, Kent, 1964; Dodd, 1973). 2. Signals attributed to certain paramagnetic metal ions are also decreased (Nebert and Mason, 1963; Swartz et al., 1973). New lines may exceptionally appear, too (Mallard, Kent, 1966). So far mostly human and mammalian tumours (hepatoma and liver tissue) induced by carcinogens have been studied. The aim of the present work was to extend these observations to a fowl tumour of viral origin."} {"id": "PMID:174378", "title": "Orientation dependence in the Epr spectra of spin labels in glycerinated muscle fibres.", "content": "Glycerinated muscle fibres labelled with a set of five-membered maleimide spin labels revealed a complex type epr spectra, which showed a reduced rate of anisotropic motion. The spectra can be interpreted in terms of the ratio of the two down-field peaks and of the hyperfine coupling constant. The spectra clearly indicated that the preferred orientation of the 2peta molecular orbital of the odd electron is perpendicular rather than parallel to the long axis of the muscle fibres. Increasing chain length between the meleimide ring and pyrrolidine nitroxide ring reduces the orientational anisotropy. Thermal denaturation destroys the orientation dependence of the epr spectra of spin labels. The Mg-ATP induced shortening of the fibres influences the spectral parameters. The fibers which had been contracted showed a modified orientation dependence of epr spectra.", "contents": "Orientation dependence in the Epr spectra of spin labels in glycerinated muscle fibres. Glycerinated muscle fibres labelled with a set of five-membered maleimide spin labels revealed a complex type epr spectra, which showed a reduced rate of anisotropic motion. The spectra can be interpreted in terms of the ratio of the two down-field peaks and of the hyperfine coupling constant. The spectra clearly indicated that the preferred orientation of the 2peta molecular orbital of the odd electron is perpendicular rather than parallel to the long axis of the muscle fibres. Increasing chain length between the meleimide ring and pyrrolidine nitroxide ring reduces the orientational anisotropy. Thermal denaturation destroys the orientation dependence of the epr spectra of spin labels. The Mg-ATP induced shortening of the fibres influences the spectral parameters. The fibers which had been contracted showed a modified orientation dependence of epr spectra."} {"id": "PMID:174379", "title": "GM2-gangliosidosis, AB variant: clinico-pathological study of a case.", "content": "Clinical and neuropathological studies of a case of AB variant GM2-gangliosidosis have been presented. The patient was a 14 months old black female infant who had \"black cherry spot\" in the retinas. The total activities of beta-galactosidase and N-acetyl-beta-hexosaminidase, as well as the proportion of hexosaminidase A and B components in her serum and leukocytes were normal when the assays were carried out with artificial fluorogenic substrate. Diagnosis of GM2-gangliosidosis AB variant was established by an abnormal increase of GM2-ganglioside in the biopsied brain tissue, similar to classical Tay-Sachs disease. Her clinical manifestation appeared to be similar but somewhat milder than those of classical Tay-Sachs disease. Light microscopic features of the cerebral biopsy were also closely similar to Tay-Sachs disease and Sandhoff disease but gliosis and neuronal loss were less pronounced. Electron microscopic study revealed numerous membranous cytoplasmic bodies (MCB) and zebra bodies in neurons. In addition, varieties of large intracytoplasmic inclusions in astrocytes, a feature distinctly different from classical Tay-Sachs disease, were observed. Numerous cytoplasmic inclusions were also present in oligodendroglia, pericytes and microglial cells.", "contents": "GM2-gangliosidosis, AB variant: clinico-pathological study of a case. Clinical and neuropathological studies of a case of AB variant GM2-gangliosidosis have been presented. The patient was a 14 months old black female infant who had \"black cherry spot\" in the retinas. The total activities of beta-galactosidase and N-acetyl-beta-hexosaminidase, as well as the proportion of hexosaminidase A and B components in her serum and leukocytes were normal when the assays were carried out with artificial fluorogenic substrate. Diagnosis of GM2-gangliosidosis AB variant was established by an abnormal increase of GM2-ganglioside in the biopsied brain tissue, similar to classical Tay-Sachs disease. Her clinical manifestation appeared to be similar but somewhat milder than those of classical Tay-Sachs disease. Light microscopic features of the cerebral biopsy were also closely similar to Tay-Sachs disease and Sandhoff disease but gliosis and neuronal loss were less pronounced. Electron microscopic study revealed numerous membranous cytoplasmic bodies (MCB) and zebra bodies in neurons. In addition, varieties of large intracytoplasmic inclusions in astrocytes, a feature distinctly different from classical Tay-Sachs disease, were observed. Numerous cytoplasmic inclusions were also present in oligodendroglia, pericytes and microglial cells."} {"id": "PMID:174380", "title": "A fine structural study of degenerative-regenerative pathology in the surgically deafferentated lateral vestibular nucleus of the rat.", "content": "An experiment was designed to examine the course of degeneration, phagocytosis, and regeneration in the central nervous system following surgical deafferentation. The anterior cerebellar vermis was ablated in young male rats. The animals were sacrificed by perfusion at postoperative times ranging from 24 hrs to 6 months. The lateral vestibular nuclei, to which the anterior cerebellar vermis projects, were processed for electron microscopy. Degenerating synaptic terminals, of the dark variety, were seen from 24 hrs to five days postoperatively. Phagocytosis of degenerating terminals occurred during this time. Degenerating axons persisted through 6 months survival, and phagocytosis of these degenerating axons were observed. Astrocyte scar formation began at 1 month postoperatively. The relative number of axosomatic synaptic terminals containing flattened vesicles (\"F\" terminals; presumed inhibitory in function) increased in operated animals. The highest F scores were found from 24 hrs to two weeks postoperatively, and then the F scores declined through six months. The significance of these sprouting activities is discussed in relation to the abortive sprouting phenomenon described by Ramon y Cajal.", "contents": "A fine structural study of degenerative-regenerative pathology in the surgically deafferentated lateral vestibular nucleus of the rat. An experiment was designed to examine the course of degeneration, phagocytosis, and regeneration in the central nervous system following surgical deafferentation. The anterior cerebellar vermis was ablated in young male rats. The animals were sacrificed by perfusion at postoperative times ranging from 24 hrs to 6 months. The lateral vestibular nuclei, to which the anterior cerebellar vermis projects, were processed for electron microscopy. Degenerating synaptic terminals, of the dark variety, were seen from 24 hrs to five days postoperatively. Phagocytosis of degenerating terminals occurred during this time. Degenerating axons persisted through 6 months survival, and phagocytosis of these degenerating axons were observed. Astrocyte scar formation began at 1 month postoperatively. The relative number of axosomatic synaptic terminals containing flattened vesicles (\"F\" terminals; presumed inhibitory in function) increased in operated animals. The highest F scores were found from 24 hrs to two weeks postoperatively, and then the F scores declined through six months. The significance of these sprouting activities is discussed in relation to the abortive sprouting phenomenon described by Ramon y Cajal."} {"id": "PMID:174381", "title": "Vascular and neuroglial changes in experimental herpes simplex encephalitis: ultrastructural study.", "content": "Generalized vascular changes and diffused proliferation of reactive microglia were observed in an experimental model of HSV encephalitis of mice. The wide spread of these changes contrasted with the localized character of virus replication and the confined areas of damaged nervous tissue. The vascular and microglial changes were precocious in animals inoculated with concentrated virus suspension (10(5.5)LD50) while they appeared late in mice inoculated with diluted virus suspension (100 LD50). After inoculation with U.V. inactivated virus no changes were seen. The results obtained in this study suggest that the vascular and microglial modifications are not related to a direct cytopathic effect of the virus but dependent on the amount of virus present in the central nervous system and linked to the virus DNA.", "contents": "Vascular and neuroglial changes in experimental herpes simplex encephalitis: ultrastructural study. Generalized vascular changes and diffused proliferation of reactive microglia were observed in an experimental model of HSV encephalitis of mice. The wide spread of these changes contrasted with the localized character of virus replication and the confined areas of damaged nervous tissue. The vascular and microglial changes were precocious in animals inoculated with concentrated virus suspension (10(5.5)LD50) while they appeared late in mice inoculated with diluted virus suspension (100 LD50). After inoculation with U.V. inactivated virus no changes were seen. The results obtained in this study suggest that the vascular and microglial modifications are not related to a direct cytopathic effect of the virus but dependent on the amount of virus present in the central nervous system and linked to the virus DNA."} {"id": "PMID:174382", "title": "A study of the perineurium in peripheral nerve pathology.", "content": "The response of the perineurium to the following experimental systems was investigated by light and electron microscopy: nerve crush, cold lesion and microinjection of (a) histamine liberator, (b) potassium cyanide, (c) lysophosphatidyl choline (LPC). Where myelin breakdown occurred, lipid globules were seen within Schwann cells, macrophages and also perineurial cells. Where increased vascular permeability occurred, proteinaceous material leaked from endoneurial vessels into the endoneurial space and later appeared between perineurial laminae. It is suggested that the normal homeostatic function of the perineurium is extended in pathology to the removal of protein and lipid debris. In this way the perineurium contributes to the restoration of the normal microenvironment of peripheral nerve fibres.", "contents": "A study of the perineurium in peripheral nerve pathology. The response of the perineurium to the following experimental systems was investigated by light and electron microscopy: nerve crush, cold lesion and microinjection of (a) histamine liberator, (b) potassium cyanide, (c) lysophosphatidyl choline (LPC). Where myelin breakdown occurred, lipid globules were seen within Schwann cells, macrophages and also perineurial cells. Where increased vascular permeability occurred, proteinaceous material leaked from endoneurial vessels into the endoneurial space and later appeared between perineurial laminae. It is suggested that the normal homeostatic function of the perineurium is extended in pathology to the removal of protein and lipid debris. In this way the perineurium contributes to the restoration of the normal microenvironment of peripheral nerve fibres."} {"id": "PMID:174383", "title": "The nasal fundus ectasia.", "content": "The object of this work has been to describe an eye anomaly consisting of a series of individual characteristics. As a name for the disorder \"the nasal fundus ectasia\" has been selected. Special attention has been paid to the bitemporal visual field defects which can easily lead to a suspicion of tumour in the region of the optic chiasm.", "contents": "The nasal fundus ectasia. The object of this work has been to describe an eye anomaly consisting of a series of individual characteristics. As a name for the disorder \"the nasal fundus ectasia\" has been selected. Special attention has been paid to the bitemporal visual field defects which can easily lead to a suspicion of tumour in the region of the optic chiasm."} {"id": "PMID:174388", "title": "Secretion of anterior pituitary hormones in man: effects of ethyl alcohol.", "content": "The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site.", "contents": "Secretion of anterior pituitary hormones in man: effects of ethyl alcohol. The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site."} {"id": "PMID:174389", "title": "Studies on the renal uptake of vitamin D3 in the mouse and the quail.", "content": "The renal uptake of labelled vitamin D3 was studied in the mouse and the quail. Upon the administration of labelled vitamin D3 autoradiographic experiments showed a specific accumulation of radioactivity in the proximal tubuli of the mouse kidney. This was still obvious 18 days after the administration. In the quail, on the other hand, the uptake in the kidney did not exceed the level of the blood. In the mouse there was a slow increase in the amount of steriod in the kidney after the injection of vitamin D3, a maximum being reached 24 hours after the administration. The amount of steroid which accumulated in the kidney was largely proportional to the injected dose of the vitamin-from doses at 4.8 ng to 4.8 mug. Column chromatography showed that most of the renal vitamin D3, was present in a non-metabolized form. Cellular fractionation showed that most radioactivity in the kidney was present in the mitochondrial and microsomal fractions. Upon sonication of the fractions most radioactivity was still bound to these particles.", "contents": "Studies on the renal uptake of vitamin D3 in the mouse and the quail. The renal uptake of labelled vitamin D3 was studied in the mouse and the quail. Upon the administration of labelled vitamin D3 autoradiographic experiments showed a specific accumulation of radioactivity in the proximal tubuli of the mouse kidney. This was still obvious 18 days after the administration. In the quail, on the other hand, the uptake in the kidney did not exceed the level of the blood. In the mouse there was a slow increase in the amount of steriod in the kidney after the injection of vitamin D3, a maximum being reached 24 hours after the administration. The amount of steroid which accumulated in the kidney was largely proportional to the injected dose of the vitamin-from doses at 4.8 ng to 4.8 mug. Column chromatography showed that most of the renal vitamin D3, was present in a non-metabolized form. Cellular fractionation showed that most radioactivity in the kidney was present in the mitochondrial and microsomal fractions. Upon sonication of the fractions most radioactivity was still bound to these particles."} {"id": "PMID:174390", "title": "Pulsatile secretion of ACTH, GH, LH and TSH in man.", "content": "Blood samples were taken every 4 min for 80 min from 5 healthy subjects. Plasma ACTH, GH, LH and TSH were estimated by radioimmunoassays. The mean peak intervals were 11, 12, 13 and 14 minutes respectively and mean peak amplitudes were 25 pg, 1.1 ng, 11 ng and 5.3 muU. Mean durations of ascending and descending limbs of the plasma patterns of these hormones were also measured. The timing of the different hormone peaks appeared to be independent.", "contents": "Pulsatile secretion of ACTH, GH, LH and TSH in man. Blood samples were taken every 4 min for 80 min from 5 healthy subjects. Plasma ACTH, GH, LH and TSH were estimated by radioimmunoassays. The mean peak intervals were 11, 12, 13 and 14 minutes respectively and mean peak amplitudes were 25 pg, 1.1 ng, 11 ng and 5.3 muU. Mean durations of ascending and descending limbs of the plasma patterns of these hormones were also measured. The timing of the different hormone peaks appeared to be independent."} {"id": "PMID:174393", "title": "Plasma myeloperoxidase and lactoferrin measured by radioimmunoassay: relations to neutrophil kinetics.", "content": "In 31 patients, covering a wide range of blood neutrophil counts and turnover rates, the plasma concentrations of myeloperoxidase and lactoferrin have been measured with radioimmunoassays and compared to neutrophil kinetic parameters, measured with DF32P-labeled neutrophils. It was found that the plasma concentrations of both proteins correlated significantly with the total number of neutrophils in the blood (TBGP=total blood granulocyte pool) as well as with the neutrophil turnover rate (GTR=granulocyte turnover rate), which is evidence that neutrophilic granulocytes are the main suppliers of myeloperoxidase and lactoferrin to the plasma. In contrast to the previously demonstrated better relationship between the GTR and plasma lysozyme, a protein also originating in neutrophil granules, both myeloperoxidase and lactoferrin correlated better with the TBGP. These differences may reflect differences in the mode of release of intragranular proteins from neutrophils to the plasma. The correlation of the plasma lactoferrin concentration with the TBGP was so good as to suggest its use in the clinical assessment of the TBGP.", "contents": "Plasma myeloperoxidase and lactoferrin measured by radioimmunoassay: relations to neutrophil kinetics. In 31 patients, covering a wide range of blood neutrophil counts and turnover rates, the plasma concentrations of myeloperoxidase and lactoferrin have been measured with radioimmunoassays and compared to neutrophil kinetic parameters, measured with DF32P-labeled neutrophils. It was found that the plasma concentrations of both proteins correlated significantly with the total number of neutrophils in the blood (TBGP=total blood granulocyte pool) as well as with the neutrophil turnover rate (GTR=granulocyte turnover rate), which is evidence that neutrophilic granulocytes are the main suppliers of myeloperoxidase and lactoferrin to the plasma. In contrast to the previously demonstrated better relationship between the GTR and plasma lysozyme, a protein also originating in neutrophil granules, both myeloperoxidase and lactoferrin correlated better with the TBGP. These differences may reflect differences in the mode of release of intragranular proteins from neutrophils to the plasma. The correlation of the plasma lactoferrin concentration with the TBGP was so good as to suggest its use in the clinical assessment of the TBGP."} {"id": "PMID:174394", "title": "Characteristics of tick-borne encephalitis virus cirulating in Poland.", "content": "An attempt of chacteristization of tick-borne encephalitis virus strains, isolated in Poland in 1955--1970, was based on the determination and analysis of neurovirulence for white mice at intracerbral and subcutaneous virus inoculation, neuroinvasion, antigenic properties, cytopathogenic abilities, susceptibility to nonspecific hemagglutination inhibitors, susceptibility to temperature of 50degree and to 2M urea. Strains isolated in different regions of the country showed certain differentiation in pathogenic and antigenic properties as well in susceptibility to nonspecific inhibitors.", "contents": "Characteristics of tick-borne encephalitis virus cirulating in Poland. An attempt of chacteristization of tick-borne encephalitis virus strains, isolated in Poland in 1955--1970, was based on the determination and analysis of neurovirulence for white mice at intracerbral and subcutaneous virus inoculation, neuroinvasion, antigenic properties, cytopathogenic abilities, susceptibility to nonspecific hemagglutination inhibitors, susceptibility to temperature of 50degree and to 2M urea. Strains isolated in different regions of the country showed certain differentiation in pathogenic and antigenic properties as well in susceptibility to nonspecific inhibitors."} {"id": "PMID:174395", "title": "The biological significance of PGO spikes in the sleeping cat.", "content": "Large-amplitude waves recorded in the pontine tegmentum, lateral geniculate body and visual cortex herald the onset and continue throughout paradoxical sleep. The role of these ponto-geniculo-occipital (PGO) waves, or spikes, has puzzled researchers since their discovery. This paper reports experiments in cats which have demonstrated that PGO spikes are essentially an epiphenomenon, an electrical sign of the activation of a \"startle network\" by the neural turmoil of paradoxical sleep. Internal stimulation provided by the bursts of neural activity which characterize paradoxical sleep produces PGO spikes in the lateral geniculate body which are identical in appearance to those elicited during synchronized and paradoxical sleep by 1.55 Hz tone bursts or taps on the cage in normal cats. Cerebellar lesions result in behavioral responses to the intrinsic startles during synchronized sleep in the form of extensor or flexor jerks of the forelimbs. The jerks occur in conjunction with each PGO spike. Identical movements can be induced in the same cats in wakefulness by such startling stimuli as dropping the cat or hissing with an aerosol can. Lesions involving the auditory-visual area permit cats to be stimulated by sound in synchronized sleep without arousal, but anterior lobe lesions produce an easily aroused animal. We postulate that the phenomena observed following cerebellar lesions are the result of alteration in the control of serotonergic neurons of the pontine raphe nuclei.", "contents": "The biological significance of PGO spikes in the sleeping cat. Large-amplitude waves recorded in the pontine tegmentum, lateral geniculate body and visual cortex herald the onset and continue throughout paradoxical sleep. The role of these ponto-geniculo-occipital (PGO) waves, or spikes, has puzzled researchers since their discovery. This paper reports experiments in cats which have demonstrated that PGO spikes are essentially an epiphenomenon, an electrical sign of the activation of a \"startle network\" by the neural turmoil of paradoxical sleep. Internal stimulation provided by the bursts of neural activity which characterize paradoxical sleep produces PGO spikes in the lateral geniculate body which are identical in appearance to those elicited during synchronized and paradoxical sleep by 1.55 Hz tone bursts or taps on the cage in normal cats. Cerebellar lesions result in behavioral responses to the intrinsic startles during synchronized sleep in the form of extensor or flexor jerks of the forelimbs. The jerks occur in conjunction with each PGO spike. Identical movements can be induced in the same cats in wakefulness by such startling stimuli as dropping the cat or hissing with an aerosol can. Lesions involving the auditory-visual area permit cats to be stimulated by sound in synchronized sleep without arousal, but anterior lobe lesions produce an easily aroused animal. We postulate that the phenomena observed following cerebellar lesions are the result of alteration in the control of serotonergic neurons of the pontine raphe nuclei."} {"id": "PMID:174396", "title": "Considerations on neurotrophic relations in the central and peripheral nervous system.", "content": "The evidence for the existence of neurotrophic (non-impulse) influences is reviewed especially with respect to choice of adequate parameters and of differentiation of neurotrophic influences from other mechanisms affecting intercellular relations. The importance of growth processes in neurotrophic control is stressed, the mechanisms being apparently similar in the central and peripheral nervous system. Collateral sprouting as a compensatory response of the neuron on one hand and the old age changes at neuromuscular synapses resulting in \"silent\" synapses and later \"silent\" terminals present phenomena indicating mechanisms of growth and arrest of growth processes in neurotrophic control.", "contents": "Considerations on neurotrophic relations in the central and peripheral nervous system. The evidence for the existence of neurotrophic (non-impulse) influences is reviewed especially with respect to choice of adequate parameters and of differentiation of neurotrophic influences from other mechanisms affecting intercellular relations. The importance of growth processes in neurotrophic control is stressed, the mechanisms being apparently similar in the central and peripheral nervous system. Collateral sprouting as a compensatory response of the neuron on one hand and the old age changes at neuromuscular synapses resulting in \"silent\" synapses and later \"silent\" terminals present phenomena indicating mechanisms of growth and arrest of growth processes in neurotrophic control."} {"id": "PMID:174413", "title": "A model for the quantitative study of Arthus (immunologic) hypersensitivity in rats.", "content": "A model of reverse passive Arthus (RPA) reaction in the pleural cavity of rats is described. The time course of development of exudate and migration of cells has been examined. It has been found to be complement dependent and dominated by polymorphonuclear cells. The reaction reaches a peak around 6 hours after challenge. Cyclic AMP levels have been measured both intracellularly and extracellularly and have been found to persist at high levels after the waning of the reaction.", "contents": "A model for the quantitative study of Arthus (immunologic) hypersensitivity in rats. A model of reverse passive Arthus (RPA) reaction in the pleural cavity of rats is described. The time course of development of exudate and migration of cells has been examined. It has been found to be complement dependent and dominated by polymorphonuclear cells. The reaction reaches a peak around 6 hours after challenge. Cyclic AMP levels have been measured both intracellularly and extracellularly and have been found to persist at high levels after the waning of the reaction."} {"id": "PMID:174415", "title": "Diagnostic applications of the fluorescent antibody method.", "content": "Reagents and equipment are now readily available to make fluorescent antibody techniques routine diagnostic procedures. Antinuclear antibodies are detectable by such methods and are useful in the diagnosis of autoimmune disease. By defining not only the site of tissue damage but also the specific components deposted at that site, immunofluorescence applied to renal biopsies has helped to elucidate the nature of otherwise similar appearing processes. Fluorescent techniques also facilitate diagnosis of such skin diseases as lupus, bullous pemphigoid and pemphigus.", "contents": "Diagnostic applications of the fluorescent antibody method. Reagents and equipment are now readily available to make fluorescent antibody techniques routine diagnostic procedures. Antinuclear antibodies are detectable by such methods and are useful in the diagnosis of autoimmune disease. By defining not only the site of tissue damage but also the specific components deposted at that site, immunofluorescence applied to renal biopsies has helped to elucidate the nature of otherwise similar appearing processes. Fluorescent techniques also facilitate diagnosis of such skin diseases as lupus, bullous pemphigoid and pemphigus."} {"id": "PMID:174416", "title": "Chronic inhalation of nickel oxide and cigarette smoke by hamsters.", "content": "Chronic inhalation of NiO and cigarette smoke (CS) by hamsters eventually caused pneumoconiosis whose development was unaffected by CS. No carcinogenic or cocarcinogenic effect of NiO and CS was observed, CS exposure increased laryngeal lesions, reduced body weight, and increased lifespan.", "contents": "Chronic inhalation of nickel oxide and cigarette smoke by hamsters. Chronic inhalation of NiO and cigarette smoke (CS) by hamsters eventually caused pneumoconiosis whose development was unaffected by CS. No carcinogenic or cocarcinogenic effect of NiO and CS was observed, CS exposure increased laryngeal lesions, reduced body weight, and increased lifespan."} {"id": "PMID:174419", "title": "Efficiency and loading characteristics of EPA's high-temperature quartz fiber filter media.", "content": "It was experimentally demonstrated that Gelman Type A and \"Microquartz\" filters are efficient collectors of nonvolatile particles at high temperatures. Submicron particles penetrated more than large particles, and most at the highest filtration velocity tested of 51 cm/sec. In all tests, however, aerosol penetration was never more than about 0.10%. Nonvolatile particles penetrated less with increasing temperature filter loading. Particles with vaporization points below the sampling temperature, including H2SO4, can vaporize, pass through the glass fiber filters, and then recondense when cooled below their dew points. Therefore, the definition of \"particulate matter\" must be based upon a prescribed temperature. Hot stack gases, sampled at different filter temperatures, should not necessarily be comparable. Particulate emission standards must involve a suitable reference temperature to allow proper enforcement. Filtration efficiencies calculated by theoretical equations change dramatically with small changes in assumed average filter fiber diameter and/or particle size (or size distribution) used in the calculations. Pinholes not visible to the naked eye do not appear to effect penetration of glass fiber filters enough to significantly alter stack sampling results. Effect of temperature on filtration of non-volatile particles simply resulted in an increasing collection of submicron particles with increasing temperature. The main problems encountered at elevated temperatures were vaporization of volatile particles and mechanical leakage of the filter holder.", "contents": "Efficiency and loading characteristics of EPA's high-temperature quartz fiber filter media. It was experimentally demonstrated that Gelman Type A and \"Microquartz\" filters are efficient collectors of nonvolatile particles at high temperatures. Submicron particles penetrated more than large particles, and most at the highest filtration velocity tested of 51 cm/sec. In all tests, however, aerosol penetration was never more than about 0.10%. Nonvolatile particles penetrated less with increasing temperature filter loading. Particles with vaporization points below the sampling temperature, including H2SO4, can vaporize, pass through the glass fiber filters, and then recondense when cooled below their dew points. Therefore, the definition of \"particulate matter\" must be based upon a prescribed temperature. Hot stack gases, sampled at different filter temperatures, should not necessarily be comparable. Particulate emission standards must involve a suitable reference temperature to allow proper enforcement. Filtration efficiencies calculated by theoretical equations change dramatically with small changes in assumed average filter fiber diameter and/or particle size (or size distribution) used in the calculations. Pinholes not visible to the naked eye do not appear to effect penetration of glass fiber filters enough to significantly alter stack sampling results. Effect of temperature on filtration of non-volatile particles simply resulted in an increasing collection of submicron particles with increasing temperature. The main problems encountered at elevated temperatures were vaporization of volatile particles and mechanical leakage of the filter holder."} {"id": "PMID:174420", "title": "Pathologic findings from the national surgical adjuvant breast project (protocol no. 4). II. The significance of regional node histology other than sinus histiocytosis in invasive mammary cancer.", "content": "The morphologic appearances of regional lymph nodes in radical mastectomy specimens obtained from 303 women entered into a prospective study of invasive breast cancer were categorized into patterns that have been considered to reflect immunologic function. An attempt was made to correlate these with 31 other histological and 8 clinical features, including short-term treatment failure (3 months to 4 years, average 24 months). No significant relationship to the latter was encountered. However, a lymphocyte predominance pattern was significantly associated with a stellate tumor border, absent cell reaction within the dominant tumor, absent sinus histocytosis of lymph nodes, combination tumor types, and a patient age of 55 years or more. A similar relationship between age of patient and sinus histiocytosis was found with the germinal center predominance pattern. In addition, this histologic appearance was associated with circumscribed tumors, severe cell reaction, and the infiltrating ductal carcinoma NOS and medullary types. Nodes with an unstimulated appearance were also found to be related to an absent cell reaction but marked sinus histiocytosis and a patient age of 45-54 years. Possible reasons for the differences between these findings and those of others relating prognostic value to such assessment of nodal histology is discussed, as are the findings of studies relevant to the identity of immunologic function with the morphologic appearance of nodal structure. The findings from this study fail to indicate any value of such nodal assessments as prognostic discriminants for breast cancer. Although longer periods of observation might alter this conclusion, such an event is regarded as unlikely.", "contents": "Pathologic findings from the national surgical adjuvant breast project (protocol no. 4). II. The significance of regional node histology other than sinus histiocytosis in invasive mammary cancer. The morphologic appearances of regional lymph nodes in radical mastectomy specimens obtained from 303 women entered into a prospective study of invasive breast cancer were categorized into patterns that have been considered to reflect immunologic function. An attempt was made to correlate these with 31 other histological and 8 clinical features, including short-term treatment failure (3 months to 4 years, average 24 months). No significant relationship to the latter was encountered. However, a lymphocyte predominance pattern was significantly associated with a stellate tumor border, absent cell reaction within the dominant tumor, absent sinus histocytosis of lymph nodes, combination tumor types, and a patient age of 55 years or more. A similar relationship between age of patient and sinus histiocytosis was found with the germinal center predominance pattern. In addition, this histologic appearance was associated with circumscribed tumors, severe cell reaction, and the infiltrating ductal carcinoma NOS and medullary types. Nodes with an unstimulated appearance were also found to be related to an absent cell reaction but marked sinus histiocytosis and a patient age of 45-54 years. Possible reasons for the differences between these findings and those of others relating prognostic value to such assessment of nodal histology is discussed, as are the findings of studies relevant to the identity of immunologic function with the morphologic appearance of nodal structure. The findings from this study fail to indicate any value of such nodal assessments as prognostic discriminants for breast cancer. Although longer periods of observation might alter this conclusion, such an event is regarded as unlikely."} {"id": "PMID:174421", "title": "Multilocular cyst of the kidney. Report of three cases with review of the literature.", "content": "Multilocular cyst of the kidney is an uncommon lesion. Approximately 70 cases are reported in the literature, with more than half occurring in children. The etiology and pathogenesis are not known, although the microscopic appearance in certain cases resembles that of Wilms' tumor. Three additional cases are presented and the literature is reviewed.", "contents": "Multilocular cyst of the kidney. Report of three cases with review of the literature. Multilocular cyst of the kidney is an uncommon lesion. Approximately 70 cases are reported in the literature, with more than half occurring in children. The etiology and pathogenesis are not known, although the microscopic appearance in certain cases resembles that of Wilms' tumor. Three additional cases are presented and the literature is reviewed."} {"id": "PMID:174422", "title": "Isolated hypoglossal nerve paralysis following influenza vaccination.", "content": "Isolated right hypoglossal (12th) nerve paralysis occurred after bivalent killed influenza vaccine (types A and B) immunization of a 7-month-old girl with cystic fibrosis. Two days after the third immunizing dose, fever and right hypoglossal paralysis developed. There were no other neurologic signs, and she recovered completely over the following three months.", "contents": "Isolated hypoglossal nerve paralysis following influenza vaccination. Isolated right hypoglossal (12th) nerve paralysis occurred after bivalent killed influenza vaccine (types A and B) immunization of a 7-month-old girl with cystic fibrosis. Two days after the third immunizing dose, fever and right hypoglossal paralysis developed. There were no other neurologic signs, and she recovered completely over the following three months."} {"id": "PMID:174423", "title": "A case of watery diarrhea, hypokalemia and hypercalcemia associated with nonulcerogenic islet cell tumor of the pancreas.", "content": "A case of watery diarrhea, hypokalemia and hypercalcemia associated with an islet cell tumor was described. A 62-year old man exhibited frequent watery diarrhea and hypokalemia for two years. He had no peptic ulcer and serum gastrin level was normal. His serum calcium was abnormally high and serum phosphate was lowered. He had secretin-like activity in his plasma. Autopsy revealed a small islet cell tumor in the pancreas and several metastatic masses in the liver. Microscopic examination revealed the tumor cell was not beta, alpha nor D cells. By electron microscopy the secretion granules of the tumor cell resembled those of S, M and T cells. It was not possible to decide which of the tree cell types was responsible for the pancreatic cholera.", "contents": "A case of watery diarrhea, hypokalemia and hypercalcemia associated with nonulcerogenic islet cell tumor of the pancreas. A case of watery diarrhea, hypokalemia and hypercalcemia associated with an islet cell tumor was described. A 62-year old man exhibited frequent watery diarrhea and hypokalemia for two years. He had no peptic ulcer and serum gastrin level was normal. His serum calcium was abnormally high and serum phosphate was lowered. He had secretin-like activity in his plasma. Autopsy revealed a small islet cell tumor in the pancreas and several metastatic masses in the liver. Microscopic examination revealed the tumor cell was not beta, alpha nor D cells. By electron microscopy the secretion granules of the tumor cell resembled those of S, M and T cells. It was not possible to decide which of the tree cell types was responsible for the pancreatic cholera."} {"id": "PMID:174425", "title": "Seasonality, natality and herd immunity in feline panleukopenia.", "content": "Feline panleukopenia (FPL) was diagnosed in 185 of 7043 feline admissions (2.63%) at a university veterinary hospital over an eight-year period. FLP has a distinct seasonal pattern, occurring during July, August and September. Seasonal peaks were noted in all the years studied. Cats less than one year of age accounted for 70% of the total morbidity. The birth of felines in the United States also assumes a distinctly seasonal pattern. Analysis of 47,786 purebred litters born during 1970-1972 revealed a peak during April, May and June with a national median of May 29. A unifying hypothesis is presented to account for the seasonal occurrence of FPL. An influx of susceptible cats occurs annually following the birth of large numbers of kittens each spring, and disappearance of maternal immunity during the next two to three months. The addition of a large number of susceptible kittens leads to the development of summertime epidemics and serves to exemplify the principles of \"herd immunity.\"", "contents": "Seasonality, natality and herd immunity in feline panleukopenia. Feline panleukopenia (FPL) was diagnosed in 185 of 7043 feline admissions (2.63%) at a university veterinary hospital over an eight-year period. FLP has a distinct seasonal pattern, occurring during July, August and September. Seasonal peaks were noted in all the years studied. Cats less than one year of age accounted for 70% of the total morbidity. The birth of felines in the United States also assumes a distinctly seasonal pattern. Analysis of 47,786 purebred litters born during 1970-1972 revealed a peak during April, May and June with a national median of May 29. A unifying hypothesis is presented to account for the seasonal occurrence of FPL. An influx of susceptible cats occurs annually following the birth of large numbers of kittens each spring, and disappearance of maternal immunity during the next two to three months. The addition of a large number of susceptible kittens leads to the development of summertime epidemics and serves to exemplify the principles of \"herd immunity.\""} {"id": "PMID:174426", "title": "Neonatal argininosuccinic aciduria with normal brain and kidney but absent liver argininosuccinate lyase activity.", "content": "An infant is described who died at 6 days of age with hyperammonemia and argininosuccinic acid in the urine. Argininosuccinic acid lyase (AL) was absent in liver, decreased in red blood cells, but normal in brain and kidney. The instability of AL in frozen stored tissues accounts for previous reports of deficient AL activity in the brain and kidney of neonates with this disease. The variation of AL activity in the tissues of this patient demonstrates that more than one gene locus either codes for the structure of this enzyme or regulates its biosynthesis in different organs.", "contents": "Neonatal argininosuccinic aciduria with normal brain and kidney but absent liver argininosuccinate lyase activity. An infant is described who died at 6 days of age with hyperammonemia and argininosuccinic acid in the urine. Argininosuccinic acid lyase (AL) was absent in liver, decreased in red blood cells, but normal in brain and kidney. The instability of AL in frozen stored tissues accounts for previous reports of deficient AL activity in the brain and kidney of neonates with this disease. The variation of AL activity in the tissues of this patient demonstrates that more than one gene locus either codes for the structure of this enzyme or regulates its biosynthesis in different organs."} {"id": "PMID:174429", "title": "Cyclic adenosine monophosphate-induced changes in the surface morphology of diapausing blastocysts and the effects on implantation.", "content": "Estrogen induces blastocyst implantation in diapausing female mice, increases uterine levels of adenyl cyclase and cyclic adenosine monphosphate (cylic AMP), and stimulates synthesis of ribonucleic acid and protein in both the uterus and blastocyst. Furthermore, the surface ultrastructure of trophoblast cells seen with scanning electron microscopy (SEM) changes with activation of the diapausing blastocyst by estrogen. Cyclic AMP-activated blastocysts were investigated with the use of SEM and compared to blastocysts activated by estrogen. Intraperitoneal administration of cyclic AMP was generally ineffective, whereas administration of cyclic AMP intraluminally in the uterus effectively mimicked the early estrogen activation. These findings are discussed in relation to other known activation changes in preimplantation blastocysts and with regard to similar findings after administration of various antiestrogens.", "contents": "Cyclic adenosine monophosphate-induced changes in the surface morphology of diapausing blastocysts and the effects on implantation. Estrogen induces blastocyst implantation in diapausing female mice, increases uterine levels of adenyl cyclase and cyclic adenosine monphosphate (cylic AMP), and stimulates synthesis of ribonucleic acid and protein in both the uterus and blastocyst. Furthermore, the surface ultrastructure of trophoblast cells seen with scanning electron microscopy (SEM) changes with activation of the diapausing blastocyst by estrogen. Cyclic AMP-activated blastocysts were investigated with the use of SEM and compared to blastocysts activated by estrogen. Intraperitoneal administration of cyclic AMP was generally ineffective, whereas administration of cyclic AMP intraluminally in the uterus effectively mimicked the early estrogen activation. These findings are discussed in relation to other known activation changes in preimplantation blastocysts and with regard to similar findings after administration of various antiestrogens."} {"id": "PMID:174430", "title": "Developments in mammography.", "content": "Mammography is presented for the primarily nonradiologic audience. A brief historical review calls attention to some of the milestones in mammography and how it has changed. Xerororadiography is discussed, as it is one of the newer developments and is rapidly gaining broad acceptance in the United States. Clinical applications are included, with a discussion of the various entities which the radiologist can identify on the mammogram. Although the mammographic examination can be extremely accurate in the hands of interested examiners, some carcinomas will not be identified; of these, some can be discovered by routine physical examination. If mammography is made to stand alone, without a physical examination, some women with breast cancer will not be identified and will not receive prompt, adequate treatment. Mammography is an adjunct and a complement to the physical examination. Breast cancer screening appears to be effective in finding small, nonpalpable tumors, many very early in their growth. Definite evidence is now available that early diagnosis of breast cancer leads to prolonged survival. There is promise of further developments in the field of mammography.", "contents": "Developments in mammography. Mammography is presented for the primarily nonradiologic audience. A brief historical review calls attention to some of the milestones in mammography and how it has changed. Xerororadiography is discussed, as it is one of the newer developments and is rapidly gaining broad acceptance in the United States. Clinical applications are included, with a discussion of the various entities which the radiologist can identify on the mammogram. Although the mammographic examination can be extremely accurate in the hands of interested examiners, some carcinomas will not be identified; of these, some can be discovered by routine physical examination. If mammography is made to stand alone, without a physical examination, some women with breast cancer will not be identified and will not receive prompt, adequate treatment. Mammography is an adjunct and a complement to the physical examination. Breast cancer screening appears to be effective in finding small, nonpalpable tumors, many very early in their growth. Definite evidence is now available that early diagnosis of breast cancer leads to prolonged survival. There is promise of further developments in the field of mammography."} {"id": "PMID:174427", "title": "Rheumatology Rounds at the Hospital for Special Surgery. Aspects of systemic lupus erythematosus: consideration of viral and genetic factors, and remarks on therapy.", "content": "The presentation of SLE in one member of a twin pair has provided the background for discussion of genetic and environmental variables involved in the pathogenesis of the syndrome. There are promising leads (developing in parallel with studies in man and in NZB mice) suggesting that SLE results from the interaction of genetic factors with an etiologic stimulus provided by type-C RNA viruses. The principles of management of SLE have been reviewed briefly.", "contents": "Rheumatology Rounds at the Hospital for Special Surgery. Aspects of systemic lupus erythematosus: consideration of viral and genetic factors, and remarks on therapy. The presentation of SLE in one member of a twin pair has provided the background for discussion of genetic and environmental variables involved in the pathogenesis of the syndrome. There are promising leads (developing in parallel with studies in man and in NZB mice) suggesting that SLE results from the interaction of genetic factors with an etiologic stimulus provided by type-C RNA viruses. The principles of management of SLE have been reviewed briefly."} {"id": "PMID:174432", "title": "Electron microscopic study of distinctive structures in peripheral blood lymphocytes obtained from twins with systemic lupus erythematosus.", "content": "Peripheral blood lymphoid cells obtained from nine twin pairs (six monozygotic and three dizygotic) in which one or both twins had systemic lupus erythematosus (SLE) were examined by electron microscopy for the occurrence of two distinctive intracytoplasmic structures-tubuloreticular structures (TRS) and tubular crystalloids (TC). TRS were found in 0.8 to 14.8% of lymphoid-cell cross sections in 9 of 11 twins with SLE and 2 clinically well but serologically abnormal twins. Lymphoid cells of twins both clinically and serologically normal did not exhibit TRS, although their monozygotic or dizygotic SLE-positive counterparts possessed these structures. Thus, the expression of TRS was more consistent with an acquired than inborn trait and appeared to correlate with disease and serologic manifestations of SLE. TC were found in 1.7 to 7.9% of lymphoid-cell cross sections in every twin examined. No correlation was recognized between clinical or laboratory data and the frequency of TC-bearing cells. The significance and the ultrastructural development of TC in the peripheral blood lymphoid cells are briefly discussed.", "contents": "Electron microscopic study of distinctive structures in peripheral blood lymphocytes obtained from twins with systemic lupus erythematosus. Peripheral blood lymphoid cells obtained from nine twin pairs (six monozygotic and three dizygotic) in which one or both twins had systemic lupus erythematosus (SLE) were examined by electron microscopy for the occurrence of two distinctive intracytoplasmic structures-tubuloreticular structures (TRS) and tubular crystalloids (TC). TRS were found in 0.8 to 14.8% of lymphoid-cell cross sections in 9 of 11 twins with SLE and 2 clinically well but serologically abnormal twins. Lymphoid cells of twins both clinically and serologically normal did not exhibit TRS, although their monozygotic or dizygotic SLE-positive counterparts possessed these structures. Thus, the expression of TRS was more consistent with an acquired than inborn trait and appeared to correlate with disease and serologic manifestations of SLE. TC were found in 1.7 to 7.9% of lymphoid-cell cross sections in every twin examined. No correlation was recognized between clinical or laboratory data and the frequency of TC-bearing cells. The significance and the ultrastructural development of TC in the peripheral blood lymphoid cells are briefly discussed."} {"id": "PMID:174433", "title": "Evolution and modes of transmission of RNA tumor viruses. Parke-Davis Award lecture.", "content": "Most vertebrates contain sets of gene sequences (virogenes) which are an integral part of the chromosomal DNA and which can code, in some instances, for the production of Type C RNA tumor viruses. These genes are transmitted from parent to progeny along with other cellular genes, and their activation from a normally reressed state may be part of the mechanism by which RNA tumor viruses produce cancer. Isolates of endogenous genetically transmitted baboon Type C viruses are morphologically and biochemically related to other mammalian Type C viruses but can clearly be distinguished from the other groups (mouse, rat, cat, etc.) by immunologic and nucleic acid hybridization criteria. Within the primates, Type C viral gene sequences have evolved as the species have evolved, with virogenes from the most closely related genera and families showing the most sequence homology; all higher primate, including man, however, do have detectable virogene sequences in their normal tissues. Type C viruses have also been transferred under natural conditions between species only remotely related phylogenetically. The results show three clear examples where viral genes from one group of animals have become incorporated into the germ line of genetically distant groups of animals (inheritance of acquired genes). Infectious Type C viruses of primates, distinct from the endogenous primate virus group, have also been isolated (woolly monkey and gibbon isolates) and can be shown to produce tumors in other primates. Related viral information (nucleic acid sequences, enzymes, and antigens) have been reported in human tumors. The significance of infectious and/or genetically transmitted viruses in naturally occurring cancer is a major focus of current research. The presence of genetically transmitted viral genes in so many vertebrate species and the evidence that they have been conserved in several distinct vertebrate lineages suggests that they may provide some normal function(s) advantageous to the species carrying them and that their potential to cause cancers is a pathologic manifestation of normal, as yet undefined, physiologic processes.", "contents": "Evolution and modes of transmission of RNA tumor viruses. Parke-Davis Award lecture. Most vertebrates contain sets of gene sequences (virogenes) which are an integral part of the chromosomal DNA and which can code, in some instances, for the production of Type C RNA tumor viruses. These genes are transmitted from parent to progeny along with other cellular genes, and their activation from a normally reressed state may be part of the mechanism by which RNA tumor viruses produce cancer. Isolates of endogenous genetically transmitted baboon Type C viruses are morphologically and biochemically related to other mammalian Type C viruses but can clearly be distinguished from the other groups (mouse, rat, cat, etc.) by immunologic and nucleic acid hybridization criteria. Within the primates, Type C viral gene sequences have evolved as the species have evolved, with virogenes from the most closely related genera and families showing the most sequence homology; all higher primate, including man, however, do have detectable virogene sequences in their normal tissues. Type C viruses have also been transferred under natural conditions between species only remotely related phylogenetically. The results show three clear examples where viral genes from one group of animals have become incorporated into the germ line of genetically distant groups of animals (inheritance of acquired genes). Infectious Type C viruses of primates, distinct from the endogenous primate virus group, have also been isolated (woolly monkey and gibbon isolates) and can be shown to produce tumors in other primates. Related viral information (nucleic acid sequences, enzymes, and antigens) have been reported in human tumors. The significance of infectious and/or genetically transmitted viruses in naturally occurring cancer is a major focus of current research. The presence of genetically transmitted viral genes in so many vertebrate species and the evidence that they have been conserved in several distinct vertebrate lineages suggests that they may provide some normal function(s) advantageous to the species carrying them and that their potential to cause cancers is a pathologic manifestation of normal, as yet undefined, physiologic processes."} {"id": "PMID:174434", "title": "The relation of infection with the hepatitis B agent to primary hepatic carcinoma.", "content": "In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.", "contents": "The relation of infection with the hepatitis B agent to primary hepatic carcinoma. In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population."} {"id": "PMID:174435", "title": "Hepatitis A. Perspectives and recent advances.", "content": "The basis for the epidemiologic and etiologic differentiation of two major forms of viral hepatitis, hepatitis A and B, was established in a series of studies undertaken between 1930 and 1970. Final recovery and visualization of the presumed etiologic agent of hepatitis A was not, however, accomplished until the technique of immune electron microscopy was applied to the examination of specimen materials collected from individuals in the early acute stages of infection. Morphologically homogeneous virus-like particles of 27 nm diameter have now been recovered from stools of patients with hepatitis A ill from a variety of sources. Antibody to these particles has been shown to develop during the course of infection with hepatitis A but not with hepatitis B and disease has been induced in nonhuman primates inoculated with purified particle containing fractions. The classification of hepatitis A virus has not been conclusively established, but it would appear to be either a parvovirus or an enterovirus.", "contents": "Hepatitis A. Perspectives and recent advances. The basis for the epidemiologic and etiologic differentiation of two major forms of viral hepatitis, hepatitis A and B, was established in a series of studies undertaken between 1930 and 1970. Final recovery and visualization of the presumed etiologic agent of hepatitis A was not, however, accomplished until the technique of immune electron microscopy was applied to the examination of specimen materials collected from individuals in the early acute stages of infection. Morphologically homogeneous virus-like particles of 27 nm diameter have now been recovered from stools of patients with hepatitis A ill from a variety of sources. Antibody to these particles has been shown to develop during the course of infection with hepatitis A but not with hepatitis B and disease has been induced in nonhuman primates inoculated with purified particle containing fractions. The classification of hepatitis A virus has not been conclusively established, but it would appear to be either a parvovirus or an enterovirus."} {"id": "PMID:174436", "title": "Structural alterations of the junctional region in extraocular muscle of dystrophic mice. I. Modifications of sole-plate nuclei.", "content": "Sole-plate nuclei of the C57Bl/6Jdy2j dystrophic mouse showed apparent selective susceptibility to various forms of structural alteration. Pyknosis and chromatin fragmentation were seen in addition to vacuolar and membranous nuclear inclusions. These were often associated with neuromuscular junctions with markedly reduced or virtually absent junctional folding. Membranous proliferations also occurred nearby sole-plate nuclei of such flattened junctions.", "contents": "Structural alterations of the junctional region in extraocular muscle of dystrophic mice. I. Modifications of sole-plate nuclei. Sole-plate nuclei of the C57Bl/6Jdy2j dystrophic mouse showed apparent selective susceptibility to various forms of structural alteration. Pyknosis and chromatin fragmentation were seen in addition to vacuolar and membranous nuclear inclusions. These were often associated with neuromuscular junctions with markedly reduced or virtually absent junctional folding. Membranous proliferations also occurred nearby sole-plate nuclei of such flattened junctions."} {"id": "PMID:174437", "title": "Structural alterations of the junctional region in extraocular muscle of dystrophic mice. II. Hypertrophy of the neuromuscular junctional apparatus.", "content": "The fine structure of end-plate abnormalities was studied in the Bar harbor C57Bl/6jdy2j dystrophic mouse. A marked increase in area and volume of junctional sarcoplasm was often apparent. Such hypertrophied end-plates were often penetrated by networks of axonal terminal branches. At times, pseudopod-like extensions of the junctional sarcoplasm encompassed and made protracted synaptic contact with the incoming axon. Such apparent remodeling of the neuromuscular apparatus might represent a compensatory cellular response to decreased impulse transmission efficiency, as might result from a flattening of the postjunctional folding seen on abnormal muscle fibers in these animals.", "contents": "Structural alterations of the junctional region in extraocular muscle of dystrophic mice. II. Hypertrophy of the neuromuscular junctional apparatus. The fine structure of end-plate abnormalities was studied in the Bar harbor C57Bl/6jdy2j dystrophic mouse. A marked increase in area and volume of junctional sarcoplasm was often apparent. Such hypertrophied end-plates were often penetrated by networks of axonal terminal branches. At times, pseudopod-like extensions of the junctional sarcoplasm encompassed and made protracted synaptic contact with the incoming axon. Such apparent remodeling of the neuromuscular apparatus might represent a compensatory cellular response to decreased impulse transmission efficiency, as might result from a flattening of the postjunctional folding seen on abnormal muscle fibers in these animals."} {"id": "PMID:174438", "title": "On the skeletal maturation of Japanese-American White hybrids.", "content": "The skeletal maturation of Japanese-American White hybrids is discussed in relation to that of Japanese and Whites. Assessment of skeletal maturation was made on 323 radiographs of 57 boys and 151 of 33 girls studied semi-longitudinally from 3 to 18 years on the basis of the Tanner-Whitehouse method (62). The skeletal maturity scores show a tendency for a greater advance in childhood for the Whites than for the hybrids and the Japanese. However, the preadolescent spurt of skeletal maturity occurs earlier in the Japanese and the hybrids than in the Whites, and the hybrids show the intermediate skeletal maturity scores between those of the Japanese and the Whites at and after adolescence.", "contents": "On the skeletal maturation of Japanese-American White hybrids. The skeletal maturation of Japanese-American White hybrids is discussed in relation to that of Japanese and Whites. Assessment of skeletal maturation was made on 323 radiographs of 57 boys and 151 of 33 girls studied semi-longitudinally from 3 to 18 years on the basis of the Tanner-Whitehouse method (62). The skeletal maturity scores show a tendency for a greater advance in childhood for the Whites than for the hybrids and the Japanese. However, the preadolescent spurt of skeletal maturity occurs earlier in the Japanese and the hybrids than in the Whites, and the hybrids show the intermediate skeletal maturity scores between those of the Japanese and the Whites at and after adolescence."} {"id": "PMID:174440", "title": "Dispersed rat parotid acinar cells. I. Morphological and functional characterization.", "content": "Morphologically and functionally intact acinar cells have been obtained from the rat parotid gland through enzymatic dispersion with pure collagenase, hyaluronidase, and trypsin as well as mild mechanical forces. Cell yields of 30-50% of the original tissue weight with over 95% acinar cells were accomplished. The cells in suspension assumed a more or less spherical shape but the intracellular polarity of organelle distribution was maintained. The cells in suspension at 37 degrees C maintained stable monovalent cationic composition but lost potassium and gained sodium rapidly upon exposure to ouabain, 10(-5) M. The intracellular amylase concentration and the patterns of secretion of amylase and of synthesis of cyclic AMP by the cells in response to adrenergic stimulation with epinephrine or isoproterenol were comparable to those of the intact gland in situ. In addition, the cells showed good O2 consumption and maintained it constant for periods up to 8 h. These cells could be used as experimental tools for in vitro studies of receptor physiology and biochemistry, cell membrane function, cellular secretory mechanisms, and other parameters of exocrine gland cell physiology.", "contents": "Dispersed rat parotid acinar cells. I. Morphological and functional characterization. Morphologically and functionally intact acinar cells have been obtained from the rat parotid gland through enzymatic dispersion with pure collagenase, hyaluronidase, and trypsin as well as mild mechanical forces. Cell yields of 30-50% of the original tissue weight with over 95% acinar cells were accomplished. The cells in suspension assumed a more or less spherical shape but the intracellular polarity of organelle distribution was maintained. The cells in suspension at 37 degrees C maintained stable monovalent cationic composition but lost potassium and gained sodium rapidly upon exposure to ouabain, 10(-5) M. The intracellular amylase concentration and the patterns of secretion of amylase and of synthesis of cyclic AMP by the cells in response to adrenergic stimulation with epinephrine or isoproterenol were comparable to those of the intact gland in situ. In addition, the cells showed good O2 consumption and maintained it constant for periods up to 8 h. These cells could be used as experimental tools for in vitro studies of receptor physiology and biochemistry, cell membrane function, cellular secretory mechanisms, and other parameters of exocrine gland cell physiology."} {"id": "PMID:174441", "title": "Dispersed rat parotid acinar cells. II. Characterization of adrenergic receptors.", "content": "The in vitro characterization of adrenergic receptors in isolated rat parotid acinar cells was accomplished through investigations of the transmembrane influxes of K and of the secretion of amylase in response to interactions of the cells with selected agonists and antagonists. Interaction of epinephrine (EPI) at concentrations of 10(-3)-10(-9) M with the alpha-adrenergic receptors resulted in rapid efflux of K from the cells. This effect was inhibited by phentolamine but not by propranolol or atropine. The process of secretion of amylase by these cells involved the activation of the beta-adrenergic receptors by the adrenergic agonists DL-isoproterenol (IPR) and EPI at similar to above concentrations. The interaction of these agonists with the beta receptors was inhibited by propranolol but not by phentolamine or atropine. Dibutyryl clclic AMP stimulated secretion of amylase at concentrations of 10(-8) M. A progressive increase in the secretory response of the cells was observed with increases in the dibutyryl cyclic AMP concentrations up to 10(-5) M. This effect was not inhibited by propranolol. This study demonstrates that dispersed rat parotid acinar cells have functionally intact adrenergic receptors and could be used as experimental tools for the studies of receptor physiology and pharmacology as well as other aspects of secretion at the cellular level.", "contents": "Dispersed rat parotid acinar cells. II. Characterization of adrenergic receptors. The in vitro characterization of adrenergic receptors in isolated rat parotid acinar cells was accomplished through investigations of the transmembrane influxes of K and of the secretion of amylase in response to interactions of the cells with selected agonists and antagonists. Interaction of epinephrine (EPI) at concentrations of 10(-3)-10(-9) M with the alpha-adrenergic receptors resulted in rapid efflux of K from the cells. This effect was inhibited by phentolamine but not by propranolol or atropine. The process of secretion of amylase by these cells involved the activation of the beta-adrenergic receptors by the adrenergic agonists DL-isoproterenol (IPR) and EPI at similar to above concentrations. The interaction of these agonists with the beta receptors was inhibited by propranolol but not by phentolamine or atropine. Dibutyryl clclic AMP stimulated secretion of amylase at concentrations of 10(-8) M. A progressive increase in the secretory response of the cells was observed with increases in the dibutyryl cyclic AMP concentrations up to 10(-5) M. This effect was not inhibited by propranolol. This study demonstrates that dispersed rat parotid acinar cells have functionally intact adrenergic receptors and could be used as experimental tools for the studies of receptor physiology and pharmacology as well as other aspects of secretion at the cellular level."} {"id": "PMID:174442", "title": "Positive inotropic effects of methoxamine: evidence for alpha-adrenergic receptors in ventricular myocardium.", "content": "The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium.", "contents": "Positive inotropic effects of methoxamine: evidence for alpha-adrenergic receptors in ventricular myocardium. The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium."} {"id": "PMID:174443", "title": "Neuropharmacological characterization of insulin-sensitive CNS glucoregulator.", "content": "Regional insulinization of the central nervous system (CNS) through the carotid artery causes an immediate decrease of the systemic blood sugar level in rats under light barbiturate anesthesia. Cervical vagotomy or intraperitoneal or intravenous atropine pretreatment results in partial inhibition of the systemic hypoglycemic response that follows intracarotid insulin injection. Intraperitoneal, intravenous, or intracarotid pretreatment with phentolamine or propranolol or intracarotid pretreatment with epinephrine had no effect on this centrally induced hypoglycemia. Intracarotid atropine injection immediately prior to intracarotid insulin injection completely abolished the systemic hypoglycemic response. Pretreatment with neostigmine administered intravenously prevented the inhibitory effect of intracarotid atropine on the hypoglycemic response that followed intracarotid insulin injection. It is consluded that the insulin-sensitive glucoregulator center of the CNS is under cholinergic influence, or its efferent pathways have a centrally located cholinergic synapsis.", "contents": "Neuropharmacological characterization of insulin-sensitive CNS glucoregulator. Regional insulinization of the central nervous system (CNS) through the carotid artery causes an immediate decrease of the systemic blood sugar level in rats under light barbiturate anesthesia. Cervical vagotomy or intraperitoneal or intravenous atropine pretreatment results in partial inhibition of the systemic hypoglycemic response that follows intracarotid insulin injection. Intraperitoneal, intravenous, or intracarotid pretreatment with phentolamine or propranolol or intracarotid pretreatment with epinephrine had no effect on this centrally induced hypoglycemia. Intracarotid atropine injection immediately prior to intracarotid insulin injection completely abolished the systemic hypoglycemic response. Pretreatment with neostigmine administered intravenously prevented the inhibitory effect of intracarotid atropine on the hypoglycemic response that followed intracarotid insulin injection. It is consluded that the insulin-sensitive glucoregulator center of the CNS is under cholinergic influence, or its efferent pathways have a centrally located cholinergic synapsis."} {"id": "PMID:174444", "title": "Effects of synthetic buffers on reflexes in the isolated frog spinal cord.", "content": "Substitution of synthetic buffers (Tris, TES, HEPES, or 3,3-dimethylglutarate) for CO2-bicarbonate buffer in Ringer solution perfusing the isolated in vitro frog spinal cord preparation altered membrane properties and reflex activity. Perfusion with Ringer solution gassed with O2 and containing synthetic bu,fers consistently produced a depolarization of motoneurons and dorsal root fibers, decreased the amplitude (and usually the duration) of ventral and dorsal root potentials, and had variable effects on motoneuron and dorsal root reflex discharges. With Tris-Ringer these discharges decreased in amplitude; with Ringer containing one of the other synthetic buffers, these discharges were augmented. All changes were reversible when the cord was returned to bicarbonate-buffered Ringer aerated with 95% O2/5% CO2. The use of a combined buffer system-one containing a synthetic buffer and bicarbonate-induced smaller or minimal changes in bioelectric activity. At present the data are insufficient to allow firm conclusions concerning the mechanisms underlying these results; but it is evident 1) that changes in PCO2 and bicarbonate concentration and 2) that the pharmacological properties of synthetic buffers are important variables.", "contents": "Effects of synthetic buffers on reflexes in the isolated frog spinal cord. Substitution of synthetic buffers (Tris, TES, HEPES, or 3,3-dimethylglutarate) for CO2-bicarbonate buffer in Ringer solution perfusing the isolated in vitro frog spinal cord preparation altered membrane properties and reflex activity. Perfusion with Ringer solution gassed with O2 and containing synthetic bu,fers consistently produced a depolarization of motoneurons and dorsal root fibers, decreased the amplitude (and usually the duration) of ventral and dorsal root potentials, and had variable effects on motoneuron and dorsal root reflex discharges. With Tris-Ringer these discharges decreased in amplitude; with Ringer containing one of the other synthetic buffers, these discharges were augmented. All changes were reversible when the cord was returned to bicarbonate-buffered Ringer aerated with 95% O2/5% CO2. The use of a combined buffer system-one containing a synthetic buffer and bicarbonate-induced smaller or minimal changes in bioelectric activity. At present the data are insufficient to allow firm conclusions concerning the mechanisms underlying these results; but it is evident 1) that changes in PCO2 and bicarbonate concentration and 2) that the pharmacological properties of synthetic buffers are important variables."} {"id": "PMID:174445", "title": "Effect of glucagon on secretin-stimulated bile flow.", "content": "The effect of glucagon on secretin-stimulated bile flow was evaluated in dogs with chronic biliary and gastric fistulas. Evaluation of the effects of secretin and glucagon alone on hepatic bile flow indicated that the calculated maximal response (CMR) values of the two agents were similar. Secretin increased the bicarbonate concentration in hepatic bile whereas glucagon did not, suggesting basic differences in mechanism of action. Administration of glucagon to secretin-stimulated bile flow produced an increase in bile flow while decreasing the bicarbonate concentration in secretin-stimulated bile. Since the maximal response for bile flow to glucagon and secretin was significantly greater than the maximal response to either agent alone, glucagon produced potentiation of secretin-stimulated bile. Glucagon increased the CMR value of secretin-stimulated bile from 513 mul/min for secretin alone to 692 mul/min for secretin and glucagon. This was associated with no significant change in the values of the respective D50S. These data suggest that glucagon produced a noncompetitive augmentation of secretin-stimulated bile flow and suggest that the two agents do not utilize the same receptor to stimulate bile flow.", "contents": "Effect of glucagon on secretin-stimulated bile flow. The effect of glucagon on secretin-stimulated bile flow was evaluated in dogs with chronic biliary and gastric fistulas. Evaluation of the effects of secretin and glucagon alone on hepatic bile flow indicated that the calculated maximal response (CMR) values of the two agents were similar. Secretin increased the bicarbonate concentration in hepatic bile whereas glucagon did not, suggesting basic differences in mechanism of action. Administration of glucagon to secretin-stimulated bile flow produced an increase in bile flow while decreasing the bicarbonate concentration in secretin-stimulated bile. Since the maximal response for bile flow to glucagon and secretin was significantly greater than the maximal response to either agent alone, glucagon produced potentiation of secretin-stimulated bile. Glucagon increased the CMR value of secretin-stimulated bile from 513 mul/min for secretin alone to 692 mul/min for secretin and glucagon. This was associated with no significant change in the values of the respective D50S. These data suggest that glucagon produced a noncompetitive augmentation of secretin-stimulated bile flow and suggest that the two agents do not utilize the same receptor to stimulate bile flow."} {"id": "PMID:174446", "title": "Contractile inactivation in frog single denervated muscle fibers.", "content": "After preliminary conditioning depolarizations, single muscle fibers of the frog were tested for ability to contract in response to depolarization by 100 mM K+ Ringer solution. Denervated fibers (6-42 days) lose their ability to produce a 100 mM K+ contracture more rapidly than do control fibers. This decrease in 100 mM K+ contracture size (inactivation) is dependent on length of exposure to and magnitude of the conditioning depolarization and on the calcium concentration in the external medium. At 0.4 mM Ca++, the inactivation is 3 times faster than at 1.5 mM Ca++. The rate of contracture loss is not correlated with fiber diameter or the number of days after failure of neuromuscular transmission, and the preliminary conditioning depolarizations do not affect the rate of terminal relaxation from the 100 mM K+ contractures.", "contents": "Contractile inactivation in frog single denervated muscle fibers. After preliminary conditioning depolarizations, single muscle fibers of the frog were tested for ability to contract in response to depolarization by 100 mM K+ Ringer solution. Denervated fibers (6-42 days) lose their ability to produce a 100 mM K+ contracture more rapidly than do control fibers. This decrease in 100 mM K+ contracture size (inactivation) is dependent on length of exposure to and magnitude of the conditioning depolarization and on the calcium concentration in the external medium. At 0.4 mM Ca++, the inactivation is 3 times faster than at 1.5 mM Ca++. The rate of contracture loss is not correlated with fiber diameter or the number of days after failure of neuromuscular transmission, and the preliminary conditioning depolarizations do not affect the rate of terminal relaxation from the 100 mM K+ contractures."} {"id": "PMID:174447", "title": "Accumulation of some secretory enzymes in venom glands of Vipera palaestinae.", "content": "Secretion of venom in the venom glands of Vipera palaestinae was studied by measuring the protein content and enzymatic activities of L-amino acid oxidase (LAO), phosphodiesterase (PDE), and benzoylarginine ethyl esterase (BAEE). These were tested in the accumulating venom and gland homogenates at 0, 2, 3, 4,6, and 15 days after an intitial emptying of the venom glands by milking. Changes in the total activities of the enzymes and in the protein concentration were found in the venom samples, but not in the homogenates, at the different intervals after milking. In the venom the total activities of LAO, PDE, and BAEE were higher the longer the time intervals from the initial milking. When the data were fit by a straight line, the fluctuations from the line were of opposite signs for LAO and PDE at the 3- and the 4-day intervals. There were no significant correlations between the specific activities or between the changes in the specific activities of any two of the enzymes at any time interval. It is concluded that each of the enzymes is secreted at a rate independent of the other two; this pattern of secretion can best be described as nonparallel.", "contents": "Accumulation of some secretory enzymes in venom glands of Vipera palaestinae. Secretion of venom in the venom glands of Vipera palaestinae was studied by measuring the protein content and enzymatic activities of L-amino acid oxidase (LAO), phosphodiesterase (PDE), and benzoylarginine ethyl esterase (BAEE). These were tested in the accumulating venom and gland homogenates at 0, 2, 3, 4,6, and 15 days after an intitial emptying of the venom glands by milking. Changes in the total activities of the enzymes and in the protein concentration were found in the venom samples, but not in the homogenates, at the different intervals after milking. In the venom the total activities of LAO, PDE, and BAEE were higher the longer the time intervals from the initial milking. When the data were fit by a straight line, the fluctuations from the line were of opposite signs for LAO and PDE at the 3- and the 4-day intervals. There were no significant correlations between the specific activities or between the changes in the specific activities of any two of the enzymes at any time interval. It is concluded that each of the enzymes is secreted at a rate independent of the other two; this pattern of secretion can best be described as nonparallel."} {"id": "PMID:174448", "title": "Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism.", "content": "Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear \"forward crossover\" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.", "contents": "Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism. Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear \"forward crossover\" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology."} {"id": "PMID:174449", "title": "Effects of an angiotensin inhibitor on adrenocortical response to angiotensin II, ACTH, and K.", "content": "A competitive inhibitor of angiotensin II has been studied in nephrectomized dogs treated with dexamethasone to suppress ACTH secretion. The inhibitor, [1-sarcosine, 8-alanine]angiotensin II (P113), has been shown by previous investigators to inhibit the pressor action of angiotensin II but not the pressor effect of other pressor agents. The present experiments demonstrate that P113 inhibits the stimulation of aldosterone secretion by angiotensin II but not by ACTH or potassium infusions. Therefore, P113 appears to be a specific inhibitor of angiotensin's action on both vascular and adrenocortical tissue. In this dog preparation, P113 has a mild nondose-related agonistic action on the blood pressure and a nonsignificant action on aldosterone secretion, although in some dogs P113 appears to have a definite agonist effect.", "contents": "Effects of an angiotensin inhibitor on adrenocortical response to angiotensin II, ACTH, and K. A competitive inhibitor of angiotensin II has been studied in nephrectomized dogs treated with dexamethasone to suppress ACTH secretion. The inhibitor, [1-sarcosine, 8-alanine]angiotensin II (P113), has been shown by previous investigators to inhibit the pressor action of angiotensin II but not the pressor effect of other pressor agents. The present experiments demonstrate that P113 inhibits the stimulation of aldosterone secretion by angiotensin II but not by ACTH or potassium infusions. Therefore, P113 appears to be a specific inhibitor of angiotensin's action on both vascular and adrenocortical tissue. In this dog preparation, P113 has a mild nondose-related agonistic action on the blood pressure and a nonsignificant action on aldosterone secretion, although in some dogs P113 appears to have a definite agonist effect."} {"id": "PMID:174450", "title": "Community alternatives to institutional care.", "content": "The Community Mental Health Center Amendments of 1975 (Public Law 94-63) mandate that federally funded mental health centers provide specific services to patients discharged from mental health facilities, including follow-up care and a system of transitional halfway houses. In addition, they must provide assistance in screening potential inpatients and provide alternative treatment when appropriate. The author stresses the need to coordinate the resources of public and private agencies through interagency planning, collaboration, and coordinated service delivery, the need to create new resources where none exist, and the need for more involvement by psychiatristis.", "contents": "Community alternatives to institutional care. The Community Mental Health Center Amendments of 1975 (Public Law 94-63) mandate that federally funded mental health centers provide specific services to patients discharged from mental health facilities, including follow-up care and a system of transitional halfway houses. In addition, they must provide assistance in screening potential inpatients and provide alternative treatment when appropriate. The author stresses the need to coordinate the resources of public and private agencies through interagency planning, collaboration, and coordinated service delivery, the need to create new resources where none exist, and the need for more involvement by psychiatristis."} {"id": "PMID:174451", "title": "Granular cell myoblastoma of the lung.", "content": "Three cases illustrate the principal clinical and roentgenographic varieties of granular cell myoblastoma (GCM) of the lung. The vast majority are small benign intrabronchial tumors without roentgenographic findings. These remain asymptomatic and are detected accidentally at autopsy, surgery, or bronchoscopy (Case III). Larger obstructing lesions (Case I) cause focal atelectasis or pneumonitis, leading to cough, expectoration, and hemoptysis. Hilar enlargement from reactive lymph node hyperplasia is common. Clinically and roentgenographically these are indistinguishable from bronchial adenomas. Least often the tumor extends entirely extrabronchially (Case II) presenting as a parahilar parenchymal asymptomatic nodule, simulating a granuloma, hamartoma, arteriovenous malformation or a neoplastic nodule.", "contents": "Granular cell myoblastoma of the lung. Three cases illustrate the principal clinical and roentgenographic varieties of granular cell myoblastoma (GCM) of the lung. The vast majority are small benign intrabronchial tumors without roentgenographic findings. These remain asymptomatic and are detected accidentally at autopsy, surgery, or bronchoscopy (Case III). Larger obstructing lesions (Case I) cause focal atelectasis or pneumonitis, leading to cough, expectoration, and hemoptysis. Hilar enlargement from reactive lymph node hyperplasia is common. Clinically and roentgenographically these are indistinguishable from bronchial adenomas. Least often the tumor extends entirely extrabronchially (Case II) presenting as a parahilar parenchymal asymptomatic nodule, simulating a granuloma, hamartoma, arteriovenous malformation or a neoplastic nodule."} {"id": "PMID:174452", "title": "Bone tumor imaging by scintigraphy of the skeleton, marrow reticuloendothelial system, and the proliferative tissue.", "content": "Paralleled clinical studies of radioisotopic imaging or tumor metastases in the bone were undertaken with Tc99m pyrophosphate, Ga67 citrate, and Tc99m sulfur colloid. All three were capable of anticipating the bone roentgenograms. A critical analysis suggested that positive delineation with Ga67 citrate would sometimes be superior to the others. This deserves further investigation. Clinically the combined use of Tc99m pyrophosphate with Ga67 for the chest areas and extremties or with Tc99m colloid for the pelvic and abdominal areas would be more frutiful in early detection and exact localization of bone metastases.", "contents": "Bone tumor imaging by scintigraphy of the skeleton, marrow reticuloendothelial system, and the proliferative tissue. Paralleled clinical studies of radioisotopic imaging or tumor metastases in the bone were undertaken with Tc99m pyrophosphate, Ga67 citrate, and Tc99m sulfur colloid. All three were capable of anticipating the bone roentgenograms. A critical analysis suggested that positive delineation with Ga67 citrate would sometimes be superior to the others. This deserves further investigation. Clinically the combined use of Tc99m pyrophosphate with Ga67 for the chest areas and extremties or with Tc99m colloid for the pelvic and abdominal areas would be more frutiful in early detection and exact localization of bone metastases."} {"id": "PMID:174453", "title": "A comparative appraisal of emphysematous cholecystitis.", "content": "There is ample evidence from this retrospective comparison to indicate that emphysematous cholecystitis does merit clinical distinction apart from acute cholecystitis. It is an acute infection of the gallbladder caused by a specific group of bacteria that may be aided by some aspect of local ischemia. Cholelithiasis does not seem to be a major factor in the pathogenesis of emphysematous cholecystitis, and this, in association with some dependence upon ischemia, may account for the predominance of this disease in males rather than females. Gangrene is a common feature of the pathologic process, and thus it is not surprising that the diagnosis of emphysematous cholecystitis implies a risk of gallbladder perforation that is five times that expected from ordinary acute cholecystitis. The key to identifying this disease is the plain abdominal roentgenogram which in most instances will make the diagnosis and provide an impetus for early operative intervention.", "contents": "A comparative appraisal of emphysematous cholecystitis. There is ample evidence from this retrospective comparison to indicate that emphysematous cholecystitis does merit clinical distinction apart from acute cholecystitis. It is an acute infection of the gallbladder caused by a specific group of bacteria that may be aided by some aspect of local ischemia. Cholelithiasis does not seem to be a major factor in the pathogenesis of emphysematous cholecystitis, and this, in association with some dependence upon ischemia, may account for the predominance of this disease in males rather than females. Gangrene is a common feature of the pathologic process, and thus it is not surprising that the diagnosis of emphysematous cholecystitis implies a risk of gallbladder perforation that is five times that expected from ordinary acute cholecystitis. The key to identifying this disease is the plain abdominal roentgenogram which in most instances will make the diagnosis and provide an impetus for early operative intervention."} {"id": "PMID:174454", "title": "On the retinal pigment epithelium of the barn owl (Tyto alba).", "content": "The fine structure of the retinal pigment epithelium (RPE) of the barn owl (Tyto alba) is described. In general it resembles that of the retinal pigment epithelium of other vertebrate animals and a high content of myeloid bodies, lipid droplets, electron dense cytosomes, and especially phagosomes is observed. The latter show different structural specializations which include membranes, tubules, filaments, granules, vesicles, and crystalloid patterns. The central part of the retina often contains a peculiar inclusion body which is separated from the cytoplasm by one or two distinct membranes and is composed of a regularly arranged tubular network which forms a three-dimensional honeycomb structure. The tubules in part are in continuation with randomly oriented and densly packed tubules and stacks of discs consisting of paired lamellae. Similar formations within secretory cells of a gland (dendritic organ) and the taste buds of catfish are discussed.", "contents": "On the retinal pigment epithelium of the barn owl (Tyto alba). The fine structure of the retinal pigment epithelium (RPE) of the barn owl (Tyto alba) is described. In general it resembles that of the retinal pigment epithelium of other vertebrate animals and a high content of myeloid bodies, lipid droplets, electron dense cytosomes, and especially phagosomes is observed. The latter show different structural specializations which include membranes, tubules, filaments, granules, vesicles, and crystalloid patterns. The central part of the retina often contains a peculiar inclusion body which is separated from the cytoplasm by one or two distinct membranes and is composed of a regularly arranged tubular network which forms a three-dimensional honeycomb structure. The tubules in part are in continuation with randomly oriented and densly packed tubules and stacks of discs consisting of paired lamellae. Similar formations within secretory cells of a gland (dendritic organ) and the taste buds of catfish are discussed."} {"id": "PMID:174455", "title": "[Postnatal development of the rat retina under DNS-inhibitor (chloroquinediphosphate) mediation (author's transl)].", "content": "The morphogenesis of retina has been studied in 1-15 day-old rats after a single injection of chloroquinediphosphate. Beside degeneration of neuroblasts, rate of development was markedly retarded as evidence by regression of the strata reticulares. Neuroblasts or receptor cells remained disorganized and were arranged in rosettes. In the inner layer containing the third neuron myelinated bodies were produced by the drug.", "contents": "[Postnatal development of the rat retina under DNS-inhibitor (chloroquinediphosphate) mediation (author's transl)]. The morphogenesis of retina has been studied in 1-15 day-old rats after a single injection of chloroquinediphosphate. Beside degeneration of neuroblasts, rate of development was markedly retarded as evidence by regression of the strata reticulares. Neuroblasts or receptor cells remained disorganized and were arranged in rosettes. In the inner layer containing the third neuron myelinated bodies were produced by the drug."} {"id": "PMID:174456", "title": "Hyperplasia of oligodendrocytes in quaking mice.", "content": "The number of neuroglial cells in selected fiber tracts of 90-day-old quaking and normal mice was determined by a combination of light and electron microscopy. Oligodendrocytes of quaking mice are normal in number in the anterior commissure and corticospinal tract (in the cervical spinal cord) but are increased two- to fourfold in the optic nerve and the fasciculi cuneatus and gracilis (in the cervical spinal cord). The nuclei and perikarya are normal in size or smaller than normal. Those tracts with the greatest hyperplasia of oligodendrocytes also have the greatest content of myelin, suggesting that cell number influences content of myelin. However, the volume of myelin per oligodendrocyte also varies, between 2 and 11% of normal, in the different tracts of the mutant. The hyperplasia of oligodendrocytes in quaking mice may arise as compensation for their decreased production of myelin and reflect a normal plasticity in the processes of myelination. If so, the mutant may be a useful system for study of the regulation of myelogenesis.", "contents": "Hyperplasia of oligodendrocytes in quaking mice. The number of neuroglial cells in selected fiber tracts of 90-day-old quaking and normal mice was determined by a combination of light and electron microscopy. Oligodendrocytes of quaking mice are normal in number in the anterior commissure and corticospinal tract (in the cervical spinal cord) but are increased two- to fourfold in the optic nerve and the fasciculi cuneatus and gracilis (in the cervical spinal cord). The nuclei and perikarya are normal in size or smaller than normal. Those tracts with the greatest hyperplasia of oligodendrocytes also have the greatest content of myelin, suggesting that cell number influences content of myelin. However, the volume of myelin per oligodendrocyte also varies, between 2 and 11% of normal, in the different tracts of the mutant. The hyperplasia of oligodendrocytes in quaking mice may arise as compensation for their decreased production of myelin and reflect a normal plasticity in the processes of myelination. If so, the mutant may be a useful system for study of the regulation of myelogenesis."} {"id": "PMID:174458", "title": "Growth of the second metacarpal according to chronological age and skeletal maturation.", "content": "In relation to chronological age and skeletal maturation, the growth of the second metacarpal is discussed based on radiographs of the right hand and wrist in 499 male and 424 female Japanese aged 1 to 18 years. When plotted against age, bone length and width present the general growth pattern of Scammon, the adolescent spurt occurring at about 13 years in the males and 11 years in the females, and the mean values are significantly larger in the males than in the females at age 15 years for length, and age 13 years for width, and later. The growth curves of both sexes are almost parallel to each other for bone length plotted against skeletal maturation. Bone width progresses in parallel in males and females until about adolescence, whereafter there is a more rapid increase in growth in the males than in the females. The mean values for length and width are almost always significantly greater in the males than in the females. The width/length index decreases rapidly until a certain period, the minimum value being at about ten years or a maturity corresponding to that age, and then increase slightly again to reach an equilibrium state on the basis of both age and skeletal maturation. At any given age, the mean values are always greater in the males than in the females. However, according to skeletal maturation, the sex differences are steadily significant at and after the skeletal maturity corresponding to about 12 years in the males and 10 years in the females.", "contents": "Growth of the second metacarpal according to chronological age and skeletal maturation. In relation to chronological age and skeletal maturation, the growth of the second metacarpal is discussed based on radiographs of the right hand and wrist in 499 male and 424 female Japanese aged 1 to 18 years. When plotted against age, bone length and width present the general growth pattern of Scammon, the adolescent spurt occurring at about 13 years in the males and 11 years in the females, and the mean values are significantly larger in the males than in the females at age 15 years for length, and age 13 years for width, and later. The growth curves of both sexes are almost parallel to each other for bone length plotted against skeletal maturation. Bone width progresses in parallel in males and females until about adolescence, whereafter there is a more rapid increase in growth in the males than in the females. The mean values for length and width are almost always significantly greater in the males than in the females. The width/length index decreases rapidly until a certain period, the minimum value being at about ten years or a maturity corresponding to that age, and then increase slightly again to reach an equilibrium state on the basis of both age and skeletal maturation. At any given age, the mean values are always greater in the males than in the females. However, according to skeletal maturation, the sex differences are steadily significant at and after the skeletal maturity corresponding to about 12 years in the males and 10 years in the females."} {"id": "PMID:174457", "title": "An ultrastructural comparison of implantation in young and senescent golden hamsters.", "content": "Implantation was compared in young (3-5 month) and senescent (14-17 month) golden hamsters at 3, 3 1/2, 4, 4 1/2, 5, and 5 1/2 days of pregnancy (post-ovulation). One hundred twenty-two embryos (89 from 22 young females and 33 from 18 senescent females) located in utero by cutting thick sections (1-3 mum), were re-embedded and thin-sectioned for electron microscopy. Ultrastructurally implantation and embryonic differentiation was delayed approximately 12 hours in the senescent hamster when compared with young hamsters at the same stage of pregnancy. Failure of the blastocyst to implant would not appear to be a major cause of the declining litter size in aged golden hamsters.", "contents": "An ultrastructural comparison of implantation in young and senescent golden hamsters. Implantation was compared in young (3-5 month) and senescent (14-17 month) golden hamsters at 3, 3 1/2, 4, 4 1/2, 5, and 5 1/2 days of pregnancy (post-ovulation). One hundred twenty-two embryos (89 from 22 young females and 33 from 18 senescent females) located in utero by cutting thick sections (1-3 mum), were re-embedded and thin-sectioned for electron microscopy. Ultrastructurally implantation and embryonic differentiation was delayed approximately 12 hours in the senescent hamster when compared with young hamsters at the same stage of pregnancy. Failure of the blastocyst to implant would not appear to be a major cause of the declining litter size in aged golden hamsters."} {"id": "PMID:174459", "title": "Demonstration of a cytochemical difference between the tubulovesicles and plasmalemma of gastric parietal cells by ATPase and NPPase reactions.", "content": "Pieces of rat and human gastric mucosa were fixed in glutaraldehyde and paraformaldehyde and were processed by the methods of Wachstein-Meisel and of Ernst for the cytochemical demonstration of adenosine triphosphatase (ATPase) and p-nitrophenylphosphatase (NPPase) respectively. Electron microscopic examination of reacted sections revealed the ATPase reaction to be localized to the plasmalemma and to mitochondrial cristae and the NPPase reaction to the plasmalemma. The tubulovesicles were unreactive. By thus demonstrating a cytochemical difference between the plasmalemma and tubulovesicle membrane, this study suggests that the tubulovesicles do not represent an extension of or reserve of mature plasmalemma. If the tubulovesicles represent a reserve of membrane that can be rapidly utilized to expand the plasmalemma, then these studies suggest that additional membrane constituents are added, activated, or unmasked in the process.", "contents": "Demonstration of a cytochemical difference between the tubulovesicles and plasmalemma of gastric parietal cells by ATPase and NPPase reactions. Pieces of rat and human gastric mucosa were fixed in glutaraldehyde and paraformaldehyde and were processed by the methods of Wachstein-Meisel and of Ernst for the cytochemical demonstration of adenosine triphosphatase (ATPase) and p-nitrophenylphosphatase (NPPase) respectively. Electron microscopic examination of reacted sections revealed the ATPase reaction to be localized to the plasmalemma and to mitochondrial cristae and the NPPase reaction to the plasmalemma. The tubulovesicles were unreactive. By thus demonstrating a cytochemical difference between the plasmalemma and tubulovesicle membrane, this study suggests that the tubulovesicles do not represent an extension of or reserve of mature plasmalemma. If the tubulovesicles represent a reserve of membrane that can be rapidly utilized to expand the plasmalemma, then these studies suggest that additional membrane constituents are added, activated, or unmasked in the process."} {"id": "PMID:174460", "title": "Relationships of foreign protein injections (hyposensitization) in atopic children to serum lipids and lipoproteins.", "content": "Foreign protein injections (hyposensitization) given for one year to human asymptomatic asthmatics did not increase their serum total lipids or lipoprotein levels, as they apparently did in rabbits fed a lipid-rich, cholesterol-poor diet. Serum total protein and immunoglobulin levels for IgA, IgM and IgG for the asthmatics and controls were no different.", "contents": "Relationships of foreign protein injections (hyposensitization) in atopic children to serum lipids and lipoproteins. Foreign protein injections (hyposensitization) given for one year to human asymptomatic asthmatics did not increase their serum total lipids or lipoprotein levels, as they apparently did in rabbits fed a lipid-rich, cholesterol-poor diet. Serum total protein and immunoglobulin levels for IgA, IgM and IgG for the asthmatics and controls were no different."} {"id": "PMID:174464", "title": "Rhinovirus and influenza type A infections as precipitants of asthma.", "content": "Specimens from 49 persons, 3 to 60 years of age, who were prone to attacks of apparently infectious asthma were cultured for viruses and bacteria during episodes of symptomatic respiratory infection from September 1972 to June 1973. Seventy-one of 128 episodes (55 per cent) of symptomatic respiratory infection occurred with asthma. Shedding of respiratory pathogens was associated with 43 of the 128 episodes, and 19 of the 43 etiologically defined episodes occurred with wheezing. Seven of 15 rhinovirus symptomatic respiratory infections were linked with asthma, as were 4 of 5 influenza type A (H3N2) and 2 of 3 respiratory syncytial virus infections. A total of 21 different rhinovirus serotypes have been identified from asthmatic patients during 2 years of study; 14 of these were associated with wheezing, indicating that the ability to cause asthma is not restricted to only a few types. Other viruses that were shed during wheezing-associated symptomatic respiratory infections included para-influenza type 3, adenovirus type 7, and 2 unidentified viruses. Although infectious asthma was not easily defined in adults and some older children, viruses that appeared to precipitate asthma were distributed among patients of widely differing ages.", "contents": "Rhinovirus and influenza type A infections as precipitants of asthma. Specimens from 49 persons, 3 to 60 years of age, who were prone to attacks of apparently infectious asthma were cultured for viruses and bacteria during episodes of symptomatic respiratory infection from September 1972 to June 1973. Seventy-one of 128 episodes (55 per cent) of symptomatic respiratory infection occurred with asthma. Shedding of respiratory pathogens was associated with 43 of the 128 episodes, and 19 of the 43 etiologically defined episodes occurred with wheezing. Seven of 15 rhinovirus symptomatic respiratory infections were linked with asthma, as were 4 of 5 influenza type A (H3N2) and 2 of 3 respiratory syncytial virus infections. A total of 21 different rhinovirus serotypes have been identified from asthmatic patients during 2 years of study; 14 of these were associated with wheezing, indicating that the ability to cause asthma is not restricted to only a few types. Other viruses that were shed during wheezing-associated symptomatic respiratory infections included para-influenza type 3, adenovirus type 7, and 2 unidentified viruses. Although infectious asthma was not easily defined in adults and some older children, viruses that appeared to precipitate asthma were distributed among patients of widely differing ages."} {"id": "PMID:174461", "title": "[Ultrastructural and histochemical study of Hamasaki-Wesenberg bodies in lymph node sarcoidosis].", "content": "Report of a histochemical and ultrastructural study of the Hamasaki-Wesenberg Bodies in ganglionic sarcoidosis. These peculiar bodies have variable form and size and are located in the ganglionic sinuses as free elements or in the histiocytes; they are found most often in cases with sarcoidosis but are not specific of this disease. The results of this study suggest that their origin is probably lysosomial and that their nature is not unlike that of ceroid or lipofuscinic pigments. The exact signification of the presence of these bodies in the lymph nodes would need deeper investigation.", "contents": "[Ultrastructural and histochemical study of Hamasaki-Wesenberg bodies in lymph node sarcoidosis]. Report of a histochemical and ultrastructural study of the Hamasaki-Wesenberg Bodies in ganglionic sarcoidosis. These peculiar bodies have variable form and size and are located in the ganglionic sinuses as free elements or in the histiocytes; they are found most often in cases with sarcoidosis but are not specific of this disease. The results of this study suggest that their origin is probably lysosomial and that their nature is not unlike that of ceroid or lipofuscinic pigments. The exact signification of the presence of these bodies in the lymph nodes would need deeper investigation."} {"id": "PMID:174465", "title": "Pretreatment clinical staging of carcinoma of the lung.", "content": "A brief history is presented outlining the development of pretreatment clinical staging of carcinoma of the lung. All segments of the medical profession are urged to use the pretreatment clinical staging of carcinoma of the lung as presented by the American Joint Committee on Cancer Staging and End Result Reporting and adopted by the International Union Against Cancer. The results of a retrospective study of clinical staging of carcinoma of the lung compared with postsurgical staging is presented. It is believed that clinical staging of carcinoma of the lung will result in improvement in diagnosis, treatment and understanding of the disease.", "contents": "Pretreatment clinical staging of carcinoma of the lung. A brief history is presented outlining the development of pretreatment clinical staging of carcinoma of the lung. All segments of the medical profession are urged to use the pretreatment clinical staging of carcinoma of the lung as presented by the American Joint Committee on Cancer Staging and End Result Reporting and adopted by the International Union Against Cancer. The results of a retrospective study of clinical staging of carcinoma of the lung compared with postsurgical staging is presented. It is believed that clinical staging of carcinoma of the lung will result in improvement in diagnosis, treatment and understanding of the disease."} {"id": "PMID:174462", "title": "[Ultrastructural study of 6 cases of ameloblastoma].", "content": "Three cases of simple ameloblastoma were studied by electron microscopy. The classical ultrastructural features of these tumors are analysed and compared with reports in the literature and the development of the enamel organ. The authors stress the presence of two cell types (light and dark) probably corresponding to different degrees of maturity. One case of cystic ameloblastoma and one of granular cell ameloblastoma are then reported. The nature of the inclusions in this latter tumour is probably mixed: lysomal and secretory, perhaps ameloblastic. Finally, a malignant ameloblastoma is described under electron microscopy, for the first time. Closely related to simple ameloblastomas, it may be distinguished only by the presence of signs of cellular degeneration and numerous mitoses, sometimes abnormal.", "contents": "[Ultrastructural study of 6 cases of ameloblastoma]. Three cases of simple ameloblastoma were studied by electron microscopy. The classical ultrastructural features of these tumors are analysed and compared with reports in the literature and the development of the enamel organ. The authors stress the presence of two cell types (light and dark) probably corresponding to different degrees of maturity. One case of cystic ameloblastoma and one of granular cell ameloblastoma are then reported. The nature of the inclusions in this latter tumour is probably mixed: lysomal and secretory, perhaps ameloblastic. Finally, a malignant ameloblastoma is described under electron microscopy, for the first time. Closely related to simple ameloblastomas, it may be distinguished only by the presence of signs of cellular degeneration and numerous mitoses, sometimes abnormal."} {"id": "PMID:174463", "title": "[Ultrastructural odontological study of a case of Papillon-Lef\u00e8vre disease].", "content": "An ultrastructural study of the teeth and alveolar bone was carried out in a case of Papillon-Lefevre disease, using sweep electron microscopy. There were structural abnormalities of the enamel, numerous zones of cement resorption, the absence of mineralisation of the parodontal fibres inserted in the cement. Osteogenesis was disturbed and the lamina dura showed a granular pattern without any defined orientation.", "contents": "[Ultrastructural odontological study of a case of Papillon-Lef\u00e8vre disease]. An ultrastructural study of the teeth and alveolar bone was carried out in a case of Papillon-Lefevre disease, using sweep electron microscopy. There were structural abnormalities of the enamel, numerous zones of cement resorption, the absence of mineralisation of the parodontal fibres inserted in the cement. Osteogenesis was disturbed and the lamina dura showed a granular pattern without any defined orientation."} {"id": "PMID:174469", "title": "[Mixed hyperlipidemia resistant to ordinary dietetic and medical treatment. 30 cases].", "content": "From 30 cases of mixed hyperlipidemia which were resistant to apparently correctly managed treatment, combining an adapted diet and Clofibrate, the authors confirmed that there is no specific clinical or laboratory picture in these cases: except for the constant presence of two beta-lipoproteins, with a high percentage of slow pre-beta, on electrophoresis on agarose, persisting throughout the length of inactive treatment. Analysis of the factors of resistance, whether exogenous and/or endogenous show that: bad adhesion to the \"anticholesterol\" diet (persistance of the supply of alcohol and/or sugar, insufficiency of unsaturated fats) and the incomplete reduction of a residual plethoric overload however minimal, constitute the two factors of resistance which are most easily picked out and overcome, but such factors are fat to be constantly causal. And in other cases, the contribution of drug interference or of considerable glycoregulation disorder remains to be excluded or discussed. In the absence of such factors or of their decisive role, a more specific cause of metabolic resistance had to be looked for. A disorder in Clofibrate mechanism, detected by gaseous chromatography in the form of an abnormal peak at C15 (clofibric acid) is found 12 hours or more after the last ingestion of the drug in certain cases. Binding of this molecule with VLDL, and perhaps with slow pre-betalipoprotens and nolonger with albumin, could explain the fault in metabolic clearance and in good metabolic utilization of this drug.", "contents": "[Mixed hyperlipidemia resistant to ordinary dietetic and medical treatment. 30 cases]. From 30 cases of mixed hyperlipidemia which were resistant to apparently correctly managed treatment, combining an adapted diet and Clofibrate, the authors confirmed that there is no specific clinical or laboratory picture in these cases: except for the constant presence of two beta-lipoproteins, with a high percentage of slow pre-beta, on electrophoresis on agarose, persisting throughout the length of inactive treatment. Analysis of the factors of resistance, whether exogenous and/or endogenous show that: bad adhesion to the \"anticholesterol\" diet (persistance of the supply of alcohol and/or sugar, insufficiency of unsaturated fats) and the incomplete reduction of a residual plethoric overload however minimal, constitute the two factors of resistance which are most easily picked out and overcome, but such factors are fat to be constantly causal. And in other cases, the contribution of drug interference or of considerable glycoregulation disorder remains to be excluded or discussed. In the absence of such factors or of their decisive role, a more specific cause of metabolic resistance had to be looked for. A disorder in Clofibrate mechanism, detected by gaseous chromatography in the form of an abnormal peak at C15 (clofibric acid) is found 12 hours or more after the last ingestion of the drug in certain cases. Binding of this molecule with VLDL, and perhaps with slow pre-betalipoprotens and nolonger with albumin, could explain the fault in metabolic clearance and in good metabolic utilization of this drug."} {"id": "PMID:174466", "title": "[Association of aniridia and Wilms' tumor. Report of two cases (author's transl)].", "content": "Authors report two new cases of association of Wilms' tumor and congenital aniridia and a review of the literature is made. Attention is called to the frequency of this association and the importance of close observation of patients with congenital aniridia in order to ensure early diagnosis of Wilms' tumor.", "contents": "[Association of aniridia and Wilms' tumor. Report of two cases (author's transl)]. Authors report two new cases of association of Wilms' tumor and congenital aniridia and a review of the literature is made. Attention is called to the frequency of this association and the importance of close observation of patients with congenital aniridia in order to ensure early diagnosis of Wilms' tumor."} {"id": "PMID:174467", "title": "[Chronic diarrhea and intestinal cytomegalic inclusion (author's transl)].", "content": "A case of chronic diarrhea resistent to treatment is presented. At autopsy a cytomegalic inclusion disease localized only in the gastrointestinal tract was found. This case seems to be a confirmation to the hypothesis that the cytomegalovirus may be cause of gastrointestinal disturbances in infants.", "contents": "[Chronic diarrhea and intestinal cytomegalic inclusion (author's transl)]. A case of chronic diarrhea resistent to treatment is presented. At autopsy a cytomegalic inclusion disease localized only in the gastrointestinal tract was found. This case seems to be a confirmation to the hypothesis that the cytomegalovirus may be cause of gastrointestinal disturbances in infants."} {"id": "PMID:174468", "title": "[Acrocephalosyndactyly (ACS) (author's transl)].", "content": "13 cases of ACS are presented: seven of them were identified as Apert's syndrome; two as Chotzen's syndrome; three as Carpenter's syndrome, and one as Pfeiffer's syndrome. These disorders have no known ethiology. However, it is necessary to look for diabetic antecedents and dermatogliphus alterations, both in the patient and the parents. An attempt to give an explanation of their hereditary penetrance is made. Frequency of associated abnormalities, mental retardation, therapeutics, prognosis, and recent encouraging results of plastic surgery of the face are reviewed.", "contents": "[Acrocephalosyndactyly (ACS) (author's transl)]. 13 cases of ACS are presented: seven of them were identified as Apert's syndrome; two as Chotzen's syndrome; three as Carpenter's syndrome, and one as Pfeiffer's syndrome. These disorders have no known ethiology. However, it is necessary to look for diabetic antecedents and dermatogliphus alterations, both in the patient and the parents. An attempt to give an explanation of their hereditary penetrance is made. Frequency of associated abnormalities, mental retardation, therapeutics, prognosis, and recent encouraging results of plastic surgery of the face are reviewed."} {"id": "PMID:174473", "title": "[Effect of methyl parathion and zineb administration on the activity of some hepatic enzymes in rats].", "content": "Male albinos rats were fed diets containing parathion-methyl or Zineb so that the average daily intake is 1/10 or 1/20 lethal dose 50, for a period of 4 or 8 weeks. The activity of hepatic microsomal enzymes, namely :aminopyrine N-demethylase, BHT oxidase, aniline hydroxylase, Butter Yellow & Amaranth reductases, NADPH-cyt. c reductase, G6P phosphatase, were measured. The activities of G6P & 6PG deshydrogenases were also determined. With the application of the parathion-methyl doses, the only effect showed is the lowering of the microsomal protein concentration.", "contents": "[Effect of methyl parathion and zineb administration on the activity of some hepatic enzymes in rats]. Male albinos rats were fed diets containing parathion-methyl or Zineb so that the average daily intake is 1/10 or 1/20 lethal dose 50, for a period of 4 or 8 weeks. The activity of hepatic microsomal enzymes, namely :aminopyrine N-demethylase, BHT oxidase, aniline hydroxylase, Butter Yellow & Amaranth reductases, NADPH-cyt. c reductase, G6P phosphatase, were measured. The activities of G6P & 6PG deshydrogenases were also determined. With the application of the parathion-methyl doses, the only effect showed is the lowering of the microsomal protein concentration."} {"id": "PMID:174471", "title": "[Purification and characterization of \"Clostridium perfringens\" BP6K-N5 strain bacteriocin N5 (author's transl)].", "content": "The bacteriocin N5 produced by Clostridium perfringens, strain BP6K-N5, after UV irradiation induction, was purified by ammonium sulfate precipitation, followed by ion-exchange chromatography on DEAE cellulose and gel filtration on Sephadex G100. By polyacrylamid-gel electrophoresis and immunodiffusion analysis the purified material was shown to be homogenous. The purified bacteriocin N5 is inactivated by proteolytic enzymes and by heat treatment at 50 degrees C for 15 minutes. It is a simple protein with a molecular weight of approximately 82.000. The protein appears to be a single polypeptide chain, as no dissociation is obtained by sodium dodecyl sulfate and beta-mercaptoethanol disc-gel-electrophoresis.", "contents": "[Purification and characterization of \"Clostridium perfringens\" BP6K-N5 strain bacteriocin N5 (author's transl)]. The bacteriocin N5 produced by Clostridium perfringens, strain BP6K-N5, after UV irradiation induction, was purified by ammonium sulfate precipitation, followed by ion-exchange chromatography on DEAE cellulose and gel filtration on Sephadex G100. By polyacrylamid-gel electrophoresis and immunodiffusion analysis the purified material was shown to be homogenous. The purified bacteriocin N5 is inactivated by proteolytic enzymes and by heat treatment at 50 degrees C for 15 minutes. It is a simple protein with a molecular weight of approximately 82.000. The protein appears to be a single polypeptide chain, as no dissociation is obtained by sodium dodecyl sulfate and beta-mercaptoethanol disc-gel-electrophoresis."} {"id": "PMID:174472", "title": "[Kinetics of setting up of a human fecal flora in germ free mice and trial of decontamination of antibiotherapy (author's transl)].", "content": "We have tried in this study to reproduce in germfree mice a bacterial equilibrium observed previously in the gastrointestinal tract of child \"L.N.\", reared in a plastic isolator. Eight bacterial strains were studied. Seven had been fortuitously introduced: Acinetobacter lwoffi LN1, Staphylococcus epidermidis LN2, Clostridium perfringens LN3, Plectridium anatum LN4, Streptococcus bovis LN5, Enterobacter cloacae LN6, Corynebacterium sp LN7. The eighth strain was purposely administered to the child in order to take advantage of an antagonism between this strain and spontaneously acquired flora. This strain is Bacillus licheniformis FD1. The gnotoxenic mice proved to be a good experimental model because we found their bacterial equilibrium comparable to that observed in child L.N. In addition, we studied the decontamination procedures of the gastrointestinal tract of mice by observing both the antagonism of B. licheniformis with bacitracin, and the action of a suitable mixture of antibiotics. Conditions for the realization of this decontamination are discussed in this study.", "contents": "[Kinetics of setting up of a human fecal flora in germ free mice and trial of decontamination of antibiotherapy (author's transl)]. We have tried in this study to reproduce in germfree mice a bacterial equilibrium observed previously in the gastrointestinal tract of child \"L.N.\", reared in a plastic isolator. Eight bacterial strains were studied. Seven had been fortuitously introduced: Acinetobacter lwoffi LN1, Staphylococcus epidermidis LN2, Clostridium perfringens LN3, Plectridium anatum LN4, Streptococcus bovis LN5, Enterobacter cloacae LN6, Corynebacterium sp LN7. The eighth strain was purposely administered to the child in order to take advantage of an antagonism between this strain and spontaneously acquired flora. This strain is Bacillus licheniformis FD1. The gnotoxenic mice proved to be a good experimental model because we found their bacterial equilibrium comparable to that observed in child L.N. In addition, we studied the decontamination procedures of the gastrointestinal tract of mice by observing both the antagonism of B. licheniformis with bacitracin, and the action of a suitable mixture of antibiotics. Conditions for the realization of this decontamination are discussed in this study."} {"id": "PMID:174476", "title": "Cyclic AMP phosphodiesterase activity in Fasciola hepatica (L.) homogenates.", "content": "The authors have studied the bahaviour of cyclic 3',5'-AMP phosphodiesterase in the 2,000 g supernatant of the Fascilola hepatica homogenate, under basal conditions and after addition of various substances. Dopamine remarkably inhibits the enzyme activity, imidazole causes a strong activation, while serotonin, theophylline, PGE1 and PGF2alpha appear to be ineffective.", "contents": "Cyclic AMP phosphodiesterase activity in Fasciola hepatica (L.) homogenates. The authors have studied the bahaviour of cyclic 3',5'-AMP phosphodiesterase in the 2,000 g supernatant of the Fascilola hepatica homogenate, under basal conditions and after addition of various substances. Dopamine remarkably inhibits the enzyme activity, imidazole causes a strong activation, while serotonin, theophylline, PGE1 and PGF2alpha appear to be ineffective."} {"id": "PMID:174480", "title": "The cerebrospinal fluid: current concepts of its formation.", "content": "Until recently it has been generally accepted that the choroid plexuses are the major source of the cerebrospinal fluid (CSF). However, data now indicate that significant contributions to the CSF are made at extrachoroidal sites. CSF production studies and 24Na transport studies in normal and plexectomized rhesus monkeys supportive of substantial extrachoroidal CSF formation will be presented. Although the exact mechanisms of CSF formation remain to be defined, ultrafiltration is probably involved to a considerable extent. Data indicative of a lymphatic-like role for the CSF will be considered.", "contents": "The cerebrospinal fluid: current concepts of its formation. Until recently it has been generally accepted that the choroid plexuses are the major source of the cerebrospinal fluid (CSF). However, data now indicate that significant contributions to the CSF are made at extrachoroidal sites. CSF production studies and 24Na transport studies in normal and plexectomized rhesus monkeys supportive of substantial extrachoroidal CSF formation will be presented. Although the exact mechanisms of CSF formation remain to be defined, ultrafiltration is probably involved to a considerable extent. Data indicative of a lymphatic-like role for the CSF will be considered."} {"id": "PMID:174487", "title": "[Study of the interaction of human serum albumin with penicillins by means of spin labels].", "content": "Interaction of 8 penicillin preparations with human serum albumin was studied with the spin-labels method and a probe. Correlation between the binding level of penicillins with human serum albumin and their effect on the spectrum of EPR of the spin-label attached to albumin was observed only with the use of a hydrophobic probe (radical III). The covalent attached marks and the hydrophobic probe may be used for rapid orienting estimation of pencillin interaction with albumin.", "contents": "[Study of the interaction of human serum albumin with penicillins by means of spin labels]. Interaction of 8 penicillin preparations with human serum albumin was studied with the spin-labels method and a probe. Correlation between the binding level of penicillins with human serum albumin and their effect on the spectrum of EPR of the spin-label attached to albumin was observed only with the use of a hydrophobic probe (radical III). The covalent attached marks and the hydrophobic probe may be used for rapid orienting estimation of pencillin interaction with albumin."} {"id": "PMID:174488", "title": "Inhibition of vesicular stomatitis virus replication by poly(2'-fluoro-2'-deoxyuridylic acid).", "content": "Poly(2'-fluoro-2'-deoxyuridylic acid) is known to be an effective inhibitor of the deoxyribonucleic acid polymerase found within the oncornaviruses. This synthetic polynucleotide was found to inhibit the replication of vesicular stomatitis virus in mouse L cells. The polymer was shown to be capable of inhibiting the viral ribonucleic acid (RNA)-dependent RNA polymerase, and it is proposed that this is the mechanism of antiviral activity. The following observations support this viewpoint: (i) the polymer is most active when added after virus adsorption; (ii) the antiviral activity is not species specific; and (iii) the polynucleotide is nontoxic to the host cell. Conventional methodologies designed to increase nucleic acid uptake by cultured cells do not show an increase in antiviral potency.", "contents": "Inhibition of vesicular stomatitis virus replication by poly(2'-fluoro-2'-deoxyuridylic acid). Poly(2'-fluoro-2'-deoxyuridylic acid) is known to be an effective inhibitor of the deoxyribonucleic acid polymerase found within the oncornaviruses. This synthetic polynucleotide was found to inhibit the replication of vesicular stomatitis virus in mouse L cells. The polymer was shown to be capable of inhibiting the viral ribonucleic acid (RNA)-dependent RNA polymerase, and it is proposed that this is the mechanism of antiviral activity. The following observations support this viewpoint: (i) the polymer is most active when added after virus adsorption; (ii) the antiviral activity is not species specific; and (iii) the polynucleotide is nontoxic to the host cell. Conventional methodologies designed to increase nucleic acid uptake by cultured cells do not show an increase in antiviral potency."} {"id": "PMID:174489", "title": "Prospective double-blind evaluation of topical adenine arabinoside in male herpes progenitalis.", "content": "Thirty-four virologically proven episodes of herpes progenitalis in 32 men were treated in a prospective double-blind study with either adenine arabinoside ointment or an identical-appearing placebo for 7 days. Clinical evaluation and quantitative virological studies were done on days 1, 3, and 8. There was a highly significant correlation between clinical response and quantitative virology. There was no difference in clinical or virological response between drug and control groups. Primary attacks tended to have higher viral excretion over the period of observation. The level of complement-fixing antibody to herpes simplex virus type 2(<1:16 versus >/=1:16) in patients with recurrent disease did not appear to alter the course of viral excretion.", "contents": "Prospective double-blind evaluation of topical adenine arabinoside in male herpes progenitalis. Thirty-four virologically proven episodes of herpes progenitalis in 32 men were treated in a prospective double-blind study with either adenine arabinoside ointment or an identical-appearing placebo for 7 days. Clinical evaluation and quantitative virological studies were done on days 1, 3, and 8. There was a highly significant correlation between clinical response and quantitative virology. There was no difference in clinical or virological response between drug and control groups. Primary attacks tended to have higher viral excretion over the period of observation. The level of complement-fixing antibody to herpes simplex virus type 2(<1:16 versus >/=1:16) in patients with recurrent disease did not appear to alter the course of viral excretion."} {"id": "PMID:174485", "title": "[A chronological study of thymic crystalline inclusions and autoimmune disorders in Swan and NZB mice (author's transl)].", "content": "Swan and NZB mice represent good animal model for human systemic erythematosus with autoimmune phenomena (antinuclear antibodies, deposits of immunoglobulins in kidney and skin). The level of circulating thymic factor, responsible for T lymphocyte differenciation, falls during the first month of life in NZB mice, during the third month in Swan mice, during the sixth month in control mice (Swiss). In Swan mice, cytoplasmic crystalline inclusions have been found within the epithelial cells which are said to have a thymosine-like activity. The time-sequence of the appearance of the crystalline inclusions has been studied in relation to the development of autoimmune disorders (antinuclear antibodies, immunoglobulins in tissues). In each group of mice, the drop in circulating thymic factor appears before the appearance of crystalline inclusions and of autoimmunisation. Therefore, these crystals appear to represent a store of circulating thymosine-like factor or of a precursor in an ageing thymus.", "contents": "[A chronological study of thymic crystalline inclusions and autoimmune disorders in Swan and NZB mice (author's transl)]. Swan and NZB mice represent good animal model for human systemic erythematosus with autoimmune phenomena (antinuclear antibodies, deposits of immunoglobulins in kidney and skin). The level of circulating thymic factor, responsible for T lymphocyte differenciation, falls during the first month of life in NZB mice, during the third month in Swan mice, during the sixth month in control mice (Swiss). In Swan mice, cytoplasmic crystalline inclusions have been found within the epithelial cells which are said to have a thymosine-like activity. The time-sequence of the appearance of the crystalline inclusions has been studied in relation to the development of autoimmune disorders (antinuclear antibodies, immunoglobulins in tissues). In each group of mice, the drop in circulating thymic factor appears before the appearance of crystalline inclusions and of autoimmunisation. Therefore, these crystals appear to represent a store of circulating thymosine-like factor or of a precursor in an ageing thymus."} {"id": "PMID:174490", "title": "Relationship of lactate dehydrogenase specificity and growth rate to lactate metabolism by Selenomonas ruminantium.", "content": "A lactate-fermenting strain of Selenomonas ruminantium (HD4) and a lactatenonfermenting strain (GA192) were examined with respect to the stereoisomers of lactate formed during glucose fermentation, the stereoisomers of lactate fermented by HD4, and the characteristics of the lactate dehydrogenases of the strains. GA192 formed L-lactate and HD4 formed L-lactate and small amounts of D-lactate from glucose. HD4 fermended L- but not D-lactate. Both strains contain nicotinamide adenine dinucleotide (NAD)-specific lactate dehydrogenases, and no NAD-independent lactate oxidation was detected. Continuous cultures of both strains grown with limiting glucose produced mainly propionate and acetate and little lactate at dilution rates less than 0.4/h, with shifts to increasing amounts of lactate and less acetate and propionate as the dilution rate was increased from 0.4/h to approximately 1/h.", "contents": "Relationship of lactate dehydrogenase specificity and growth rate to lactate metabolism by Selenomonas ruminantium. A lactate-fermenting strain of Selenomonas ruminantium (HD4) and a lactatenonfermenting strain (GA192) were examined with respect to the stereoisomers of lactate formed during glucose fermentation, the stereoisomers of lactate fermented by HD4, and the characteristics of the lactate dehydrogenases of the strains. GA192 formed L-lactate and HD4 formed L-lactate and small amounts of D-lactate from glucose. HD4 fermended L- but not D-lactate. Both strains contain nicotinamide adenine dinucleotide (NAD)-specific lactate dehydrogenases, and no NAD-independent lactate oxidation was detected. Continuous cultures of both strains grown with limiting glucose produced mainly propionate and acetate and little lactate at dilution rates less than 0.4/h, with shifts to increasing amounts of lactate and less acetate and propionate as the dilution rate was increased from 0.4/h to approximately 1/h."} {"id": "PMID:174491", "title": "Tetramethyl-p-phenylenediamine oxidase reaction in Azotobacter vinelandii.", "content": "It was possible to quantitate the tetramethyl-p-phenylenediamine (TMPD) oxidase reaction in Azotobacter vinelandii strain O using turbidimetrically standarized resting cell suspensions. The Q(O2) value obtained for whole cell oxidation of ascorbate-TMPD appeared to reflect the full measure of the high respiratory oxidative capability usually exhibited by this genera of organisms. The Q(O2) value for the TMPD oxidase reaction ranged from 1,700 to 2,000 and this value was equivalent to that obtained for the oxidation of the growth substrate, e.g., acetate. The kinetic analyses for TMPD oxidation by whole cells was similar to that obtained for the \"particulate\" A. vinelandii electron transport particle, that fraction which TMPD oxidase activity is exclusively associated with. Under the conditions used, there appeared to be no permeability problems; TMPD (reduced by ascorbate) readily penetrated the cell and oxidized at a rate comparable to that of the growth substrate. This, however, was not true for the oxidation of another electron donor, 2,6-dichloroindophenol, whose whole cell Q(O2) values, under comparable conditions, were twofold lower. The TMPD oxidase activity in A. vinelandii whole cells was found to be affected by the physiological growth conditions, and resting cells obtained from cells grown on sucrose, either under nitrogen-fixing conditions or on nitrate as the combined nitrogen source, exhibited low TMPD oxidase rates. Such low TMPD oxidase rates were also noted for chemically induced pleomorphic A. vinelandii cells, which suggests that modified growth conditions can (i) alter the nature of the intracellular terminal oxidase formed (or induced), or (ii) alter surface permeability, depending upon the growth conditions used. Preliminary studies on the quantitative TMPD oxidation reaction in mutant whole cells of both Azotobacter and a well-known Mucor bacilliformis strain AY1, deficient in cytochrome oxidase activity, showed this assay can be very useful for detecting respiratory deficiencies in the metabolism of whole cells.", "contents": "Tetramethyl-p-phenylenediamine oxidase reaction in Azotobacter vinelandii. It was possible to quantitate the tetramethyl-p-phenylenediamine (TMPD) oxidase reaction in Azotobacter vinelandii strain O using turbidimetrically standarized resting cell suspensions. The Q(O2) value obtained for whole cell oxidation of ascorbate-TMPD appeared to reflect the full measure of the high respiratory oxidative capability usually exhibited by this genera of organisms. The Q(O2) value for the TMPD oxidase reaction ranged from 1,700 to 2,000 and this value was equivalent to that obtained for the oxidation of the growth substrate, e.g., acetate. The kinetic analyses for TMPD oxidation by whole cells was similar to that obtained for the \"particulate\" A. vinelandii electron transport particle, that fraction which TMPD oxidase activity is exclusively associated with. Under the conditions used, there appeared to be no permeability problems; TMPD (reduced by ascorbate) readily penetrated the cell and oxidized at a rate comparable to that of the growth substrate. This, however, was not true for the oxidation of another electron donor, 2,6-dichloroindophenol, whose whole cell Q(O2) values, under comparable conditions, were twofold lower. The TMPD oxidase activity in A. vinelandii whole cells was found to be affected by the physiological growth conditions, and resting cells obtained from cells grown on sucrose, either under nitrogen-fixing conditions or on nitrate as the combined nitrogen source, exhibited low TMPD oxidase rates. Such low TMPD oxidase rates were also noted for chemically induced pleomorphic A. vinelandii cells, which suggests that modified growth conditions can (i) alter the nature of the intracellular terminal oxidase formed (or induced), or (ii) alter surface permeability, depending upon the growth conditions used. Preliminary studies on the quantitative TMPD oxidation reaction in mutant whole cells of both Azotobacter and a well-known Mucor bacilliformis strain AY1, deficient in cytochrome oxidase activity, showed this assay can be very useful for detecting respiratory deficiencies in the metabolism of whole cells."} {"id": "PMID:174496", "title": "Combinations of antimicrobial agents. I. The in vitro sensitivity of 100 strains of Pseudomonas aeruginosa to polymyxin B, colistin, carbenicillin, gentamicin and doxycycline and to various combinations of these antibiotics.", "content": "The MICs for 100 strains of Pseudomonas aeruginosa were determined for polymyxin B, colistin, carbenicillin, gentamicin and doxycycline and various combinations of these antibiotics. This study was carried out by means of a tube dilution method. Additive actions were observed in the combinations of polymyxin B plus carbenicillin, polymyxin B plus gentamicin, polymyxin B plus doxycycline, carbenicillin plus doxycycline and gentamicin plus doxycycline. A synergistic action was observed for the combinations of colistin plus carbenicillin, colistin plus gentamicin, colistin plus doxycycline and carbenicillin plus gentamicin. In none of the combinations was any antagonistic action encountered. Numerous reasons for using combined antibiotic treatment are listed. The results were obtained exclusively in in vitro investigations.", "contents": "Combinations of antimicrobial agents. I. The in vitro sensitivity of 100 strains of Pseudomonas aeruginosa to polymyxin B, colistin, carbenicillin, gentamicin and doxycycline and to various combinations of these antibiotics. The MICs for 100 strains of Pseudomonas aeruginosa were determined for polymyxin B, colistin, carbenicillin, gentamicin and doxycycline and various combinations of these antibiotics. This study was carried out by means of a tube dilution method. Additive actions were observed in the combinations of polymyxin B plus carbenicillin, polymyxin B plus gentamicin, polymyxin B plus doxycycline, carbenicillin plus doxycycline and gentamicin plus doxycycline. A synergistic action was observed for the combinations of colistin plus carbenicillin, colistin plus gentamicin, colistin plus doxycycline and carbenicillin plus gentamicin. In none of the combinations was any antagonistic action encountered. Numerous reasons for using combined antibiotic treatment are listed. The results were obtained exclusively in in vitro investigations."} {"id": "PMID:174497", "title": "Malignant hepatoma associated with acquired hepatic cutaneous porphyria.", "content": "A 60-year-old woman with a three-year history of an acquired hepatic cutaneous porphyria was discovered to have a porphyrin-producing malignant hepatoma. An attempt was made to treat her with fluorouracil perfused through a hepatic artery catheter. It did not produce shrinkage of the tumor, but the patient remains alive and ambulant a year after the infusion, although her skin lesions (scarring, bulla formation, and hyperpigmentation) on the fingers, back of hands, and face persist and she continues to excrete abnormally high quantities of porphyrin in her feces.", "contents": "Malignant hepatoma associated with acquired hepatic cutaneous porphyria. A 60-year-old woman with a three-year history of an acquired hepatic cutaneous porphyria was discovered to have a porphyrin-producing malignant hepatoma. An attempt was made to treat her with fluorouracil perfused through a hepatic artery catheter. It did not produce shrinkage of the tumor, but the patient remains alive and ambulant a year after the infusion, although her skin lesions (scarring, bulla formation, and hyperpigmentation) on the fingers, back of hands, and face persist and she continues to excrete abnormally high quantities of porphyrin in her feces."} {"id": "PMID:174498", "title": "[Electron microscopical investigation of rhinoscleroma (author's transl)].", "content": "A boy from Togo with a resistent Rhinoscleroma was observed. The specific granuloma was examinated by histological and electron microscopic methods. The plasma cells form fibrillary material or guttate Russel bodies in the rough endoplasmatic reticulum. The morphology of Mikulicz-cells and Klebsiella rhinoscleromatis is described. The cells are supposed to be (histiocytic) macrophages. The surface of the germs is coated with a fimbria-like radiate substance which in the vacuoles of the cells is crosslinked. This material could be the eliciting antigen for the formation of Russel bodies. These bodies then may represent immune substances bound within the cell.", "contents": "[Electron microscopical investigation of rhinoscleroma (author's transl)]. A boy from Togo with a resistent Rhinoscleroma was observed. The specific granuloma was examinated by histological and electron microscopic methods. The plasma cells form fibrillary material or guttate Russel bodies in the rough endoplasmatic reticulum. The morphology of Mikulicz-cells and Klebsiella rhinoscleromatis is described. The cells are supposed to be (histiocytic) macrophages. The surface of the germs is coated with a fimbria-like radiate substance which in the vacuoles of the cells is crosslinked. This material could be the eliciting antigen for the formation of Russel bodies. These bodies then may represent immune substances bound within the cell."} {"id": "PMID:174499", "title": "Histophysiology of the vegetative peripheral nervous system of skin.", "content": "Preterminal nerve fibers of the peripheral vegetative nervous system make inmediate contact (neuro-effector-areas) to interstitial cells (I.C.). This connection is characterized through a common glycocalyx with the nerve fiber. The I.C. are specific innervated cells and differ morphologically from Schwann-cells, fibrocytes, and histiocytes. The I.C. are able to come into morphologically different contacts with neighbouring cells by microvilli-like cell protrusions. These neighbouring cells then are able to contact other cells by themselves. The results are interpreted in the sense of electro-mechanical feed-back system of information processing in the vegetative periphery.", "contents": "Histophysiology of the vegetative peripheral nervous system of skin. Preterminal nerve fibers of the peripheral vegetative nervous system make inmediate contact (neuro-effector-areas) to interstitial cells (I.C.). This connection is characterized through a common glycocalyx with the nerve fiber. The I.C. are specific innervated cells and differ morphologically from Schwann-cells, fibrocytes, and histiocytes. The I.C. are able to come into morphologically different contacts with neighbouring cells by microvilli-like cell protrusions. These neighbouring cells then are able to contact other cells by themselves. The results are interpreted in the sense of electro-mechanical feed-back system of information processing in the vegetative periphery."} {"id": "PMID:174500", "title": "Estrogen receptor and natural course of breast cancer.", "content": "The tumors from approximately 50% of patients with breast cancer contained estrogen receptor (ER). ER appeared more often and at higher levels in the tumors of postmenopausal women. Eleven out of 12 patients who had multiple ER assays from various metastatic sites showed no significant discrepancies in ER values. ER level appears to decrease as the duration of metastatic cancer increase. Patients with ER in the tumor more frequently have bone metastases than those without ER. Visceral metastases occurred more often with ER negative patients and appeared to have a more malignant course with significant shorter survival.", "contents": "Estrogen receptor and natural course of breast cancer. The tumors from approximately 50% of patients with breast cancer contained estrogen receptor (ER). ER appeared more often and at higher levels in the tumors of postmenopausal women. Eleven out of 12 patients who had multiple ER assays from various metastatic sites showed no significant discrepancies in ER values. ER level appears to decrease as the duration of metastatic cancer increase. Patients with ER in the tumor more frequently have bone metastases than those without ER. Visceral metastases occurred more often with ER negative patients and appeared to have a more malignant course with significant shorter survival."} {"id": "PMID:174501", "title": "Some steric factors affecting smooth muscle relaxation by cAMP analogs.", "content": "The inhibitory potency of equimolar concentrations of cyclic adenosine monophosphate (cAMP) and three of its butyrylated derivatives; N6, O2'-dibutyryl cAMP (DBcAMP), N6-monobutyryl cAMP (N6MBcAMP) and O2' monobutyryl cAMP (O2' MBcAMP) was determined in isolated guinea pig ileal and aortic smooth muscle. Substitution in the N6 position did not markedly alter the inhibitory action of cAMP in these smooth muscles. However, an increase in the effectiveness of low concentrations of epinephrine in aorta was noted in the presence of the N6 substituted derivatives (0.1 mM). Addition of a butyryl group to the O2' position greatly decreased the activity of cAMP in both intestinal and vascular smooth muscle. The character of smooth muscle relaxation shown by cAMP and its analogs is very similar to that shown by adenosine and its analogs. These substances all appear to be acting in the same manner to relax intestinal and aortic smooth muscle.", "contents": "Some steric factors affecting smooth muscle relaxation by cAMP analogs. The inhibitory potency of equimolar concentrations of cyclic adenosine monophosphate (cAMP) and three of its butyrylated derivatives; N6, O2'-dibutyryl cAMP (DBcAMP), N6-monobutyryl cAMP (N6MBcAMP) and O2' monobutyryl cAMP (O2' MBcAMP) was determined in isolated guinea pig ileal and aortic smooth muscle. Substitution in the N6 position did not markedly alter the inhibitory action of cAMP in these smooth muscles. However, an increase in the effectiveness of low concentrations of epinephrine in aorta was noted in the presence of the N6 substituted derivatives (0.1 mM). Addition of a butyryl group to the O2' position greatly decreased the activity of cAMP in both intestinal and vascular smooth muscle. The character of smooth muscle relaxation shown by cAMP and its analogs is very similar to that shown by adenosine and its analogs. These substances all appear to be acting in the same manner to relax intestinal and aortic smooth muscle."} {"id": "PMID:174502", "title": "Acute idiopathic polyneuritis caused by cytomegalovirus.", "content": "Cytomegalovirus was isolated from the PBBC from a patient with acute idiopathic polyneuritis. Viremia occurred during the early phase of the neurologic disease, preceding viruria, and was accompanied by specific CMV-IgM antibodies, which indicates a recently acquired infection. Complement fixing antibodies to CMV remained stable throughout the illness at a relatively low titer. Previously, CMV has been associated with acute idiopathic polyneuritis on the indirect evidence of rising or elevated titers of complement fixing antibodies or isolation of virus from urine or saliva or both. Our findings provide direct evidence for the causative role of CMV in acute idiopathic polyneuritis.", "contents": "Acute idiopathic polyneuritis caused by cytomegalovirus. Cytomegalovirus was isolated from the PBBC from a patient with acute idiopathic polyneuritis. Viremia occurred during the early phase of the neurologic disease, preceding viruria, and was accompanied by specific CMV-IgM antibodies, which indicates a recently acquired infection. Complement fixing antibodies to CMV remained stable throughout the illness at a relatively low titer. Previously, CMV has been associated with acute idiopathic polyneuritis on the indirect evidence of rising or elevated titers of complement fixing antibodies or isolation of virus from urine or saliva or both. Our findings provide direct evidence for the causative role of CMV in acute idiopathic polyneuritis."} {"id": "PMID:174514", "title": "[Observations on tumor-associated fibrinolysis in human breast-cancer (author's transl)].", "content": "In 30 cases of breast-cancer, including 24 primary cases, the tumor-associted fibrinolysis was investigated using agar plate method. In 60% of the tissue sample fibrinolytic activity was found. No activity could be detected in the remaining 40%. There was evidence of a positive correlation between tumor-associated fibrinolysis and tumor size as well as the rate of axilla metastases. Among the fibrinolytic active cases there was a disproporionate number of adenocarcinoma, whereas in the inactive collective the solid and scirrhous carcinoma prevailed. There was no relation between the tumor-associated fibrinolysis and the percentage of tumor cells in the tissue. The firbinolytic inactive tumors showed a better histopathological adaptation to the surrounding tissue than the active ones. There was less small-cell infiltrate in the stroma of the fibrinolytic active tumors than in the inactive cases. No significant difference was found in the form of growth and the occurence of fibre structure. For clinical assessment a longer period of observation and a larger study are necessary.", "contents": "[Observations on tumor-associated fibrinolysis in human breast-cancer (author's transl)]. In 30 cases of breast-cancer, including 24 primary cases, the tumor-associted fibrinolysis was investigated using agar plate method. In 60% of the tissue sample fibrinolytic activity was found. No activity could be detected in the remaining 40%. There was evidence of a positive correlation between tumor-associated fibrinolysis and tumor size as well as the rate of axilla metastases. Among the fibrinolytic active cases there was a disproporionate number of adenocarcinoma, whereas in the inactive collective the solid and scirrhous carcinoma prevailed. There was no relation between the tumor-associated fibrinolysis and the percentage of tumor cells in the tissue. The firbinolytic inactive tumors showed a better histopathological adaptation to the surrounding tissue than the active ones. There was less small-cell infiltrate in the stroma of the fibrinolytic active tumors than in the inactive cases. No significant difference was found in the form of growth and the occurence of fibre structure. For clinical assessment a longer period of observation and a larger study are necessary."} {"id": "PMID:174515", "title": "Significance of tissue estrogen receptors in the strategy of breast cancer treatment.", "content": "Using evidences of estrogen receptors in mammary tumor tissues it was tried 1. to find substances which inhibit the tumor growth by their binding to the estrogen receptors; 2. to predict responsiveness to endocrine therapy; and 3. to find a definition of an improved therapeutic strategy in breast cancer. There is a continuously increasing rate of receptor positive tumors, caused by an improved technique of determination and tissue handling. Estrogen receptors were detected in 73 per cent of all primary mammary tumors and 58 per cent of metastatic tumors respectively. As new therapeutic substances nafoxidine and Estracyt were tested in controlled clinical trials. To get exact data about hormonal sensitivity further quantitative investigations of receptor activities of mammary tumors and their therapeutical responsiveness have to be done. As a new step in the strategy of breast cancer therapy based on receptor determinations a combined therapy with hormones and cytotoxic chemotherapeutics has to be checked in clinical trials in uture.", "contents": "Significance of tissue estrogen receptors in the strategy of breast cancer treatment. Using evidences of estrogen receptors in mammary tumor tissues it was tried 1. to find substances which inhibit the tumor growth by their binding to the estrogen receptors; 2. to predict responsiveness to endocrine therapy; and 3. to find a definition of an improved therapeutic strategy in breast cancer. There is a continuously increasing rate of receptor positive tumors, caused by an improved technique of determination and tissue handling. Estrogen receptors were detected in 73 per cent of all primary mammary tumors and 58 per cent of metastatic tumors respectively. As new therapeutic substances nafoxidine and Estracyt were tested in controlled clinical trials. To get exact data about hormonal sensitivity further quantitative investigations of receptor activities of mammary tumors and their therapeutical responsiveness have to be done. As a new step in the strategy of breast cancer therapy based on receptor determinations a combined therapy with hormones and cytotoxic chemotherapeutics has to be checked in clinical trials in uture."} {"id": "PMID:174516", "title": "Steroid hormone receptors in human breast cancer and clinical correlations.", "content": "Human breast cancer was studied by in vitro techniques on tissue slices and extracts for a specific binding of estradiol and dihydrotestosterone. Estradiol receptors were found in 50 percent of patients in the premenopausal group and in 47 percent of patients in the postmenopausal group. The incidence of receptors in patients with metastatic disease was 32.5 percent. In 18 of 35 patients who were positive for receptor sites a remission was observed after a variety of endocrine treatment regimens. In contrast only 3 patients out of 43 with a negative binding pattern responded to treatment with nafoxidine for a very short time. The best correlation was found in the ovariectomized group. Between the responders and the nonresonders there is no difference in the quantitative receptor content. The same is valid in view of the duration of the remission.", "contents": "Steroid hormone receptors in human breast cancer and clinical correlations. Human breast cancer was studied by in vitro techniques on tissue slices and extracts for a specific binding of estradiol and dihydrotestosterone. Estradiol receptors were found in 50 percent of patients in the premenopausal group and in 47 percent of patients in the postmenopausal group. The incidence of receptors in patients with metastatic disease was 32.5 percent. In 18 of 35 patients who were positive for receptor sites a remission was observed after a variety of endocrine treatment regimens. In contrast only 3 patients out of 43 with a negative binding pattern responded to treatment with nafoxidine for a very short time. The best correlation was found in the ovariectomized group. Between the responders and the nonresonders there is no difference in the quantitative receptor content. The same is valid in view of the duration of the remission."} {"id": "PMID:174517", "title": "Estimation of high affinity estradiol binding sites in the human breast cancer.", "content": "The specific estrogen binding capacity of the cytosol has been investigated in 51 human breast cancers (49 women, 2 men). The estrogen binding sites of the cytosol has been analysed by Korenman's dextrancoated charcoal technique. Several methods have been used in order to distinguish the specific estrogen binding sites and the unspecific binding: temperature differentiation and saturation of the binding sites with nonlabelled estrogen or its antagonist Clomid. It has been concluded that the differentiation of the estradiol binding sites (specific or unspecific) with the elevated temperature effect or the additon of Clomid may be helpful only as a qualitative test. The elevated temperature of Clomid may influence the increase of the unspecific estradiol binding. The most suitable method to eliminate the unspecific binding of estradiol is the saturation of cytosol from control samples with non-radioactive estradiol-17-beta. The specific estrogen binding capacity of the cytosols of different tumours varied over a wide range (0--840 fM E2/mg protein). It has been found that among 51 persons there were 31 patients (61%) with measureable amounts of high affinity estradiol binding sites in cancerous tissues. In 20 cases (39%) the existence of estradiol specific binding sites could not be observed.", "contents": "Estimation of high affinity estradiol binding sites in the human breast cancer. The specific estrogen binding capacity of the cytosol has been investigated in 51 human breast cancers (49 women, 2 men). The estrogen binding sites of the cytosol has been analysed by Korenman's dextrancoated charcoal technique. Several methods have been used in order to distinguish the specific estrogen binding sites and the unspecific binding: temperature differentiation and saturation of the binding sites with nonlabelled estrogen or its antagonist Clomid. It has been concluded that the differentiation of the estradiol binding sites (specific or unspecific) with the elevated temperature effect or the additon of Clomid may be helpful only as a qualitative test. The elevated temperature of Clomid may influence the increase of the unspecific estradiol binding. The most suitable method to eliminate the unspecific binding of estradiol is the saturation of cytosol from control samples with non-radioactive estradiol-17-beta. The specific estrogen binding capacity of the cytosols of different tumours varied over a wide range (0--840 fM E2/mg protein). It has been found that among 51 persons there were 31 patients (61%) with measureable amounts of high affinity estradiol binding sites in cancerous tissues. In 20 cases (39%) the existence of estradiol specific binding sites could not be observed."} {"id": "PMID:174518", "title": "Estradiol receptor activity in tissues of human breast cancer.", "content": "Using the method for receptor determination recommended by the EORTC breast, cancer group we found 33.8% of our tissue specimen experimentally estradiol sensitive. No relation could be seen between receptor binding ability of the tumor tissues and lymph node involvement, tumor histology, clinical stages of the disease and menopausal state of the patients, respectively. In most cases primary tumor tissues and tissues of invaded lymph nodes show a corresponding behaviour in relation to estradiol uptake. The differences observed in the effects of various antiestrogenic substances on estradiol binding ability can not be explained at present.", "contents": "Estradiol receptor activity in tissues of human breast cancer. Using the method for receptor determination recommended by the EORTC breast, cancer group we found 33.8% of our tissue specimen experimentally estradiol sensitive. No relation could be seen between receptor binding ability of the tumor tissues and lymph node involvement, tumor histology, clinical stages of the disease and menopausal state of the patients, respectively. In most cases primary tumor tissues and tissues of invaded lymph nodes show a corresponding behaviour in relation to estradiol uptake. The differences observed in the effects of various antiestrogenic substances on estradiol binding ability can not be explained at present."} {"id": "PMID:174519", "title": "[Presence of RNA-and DNA-tumor viruses within a cell line from mouse spleen and thymus (author's transl)].", "content": "Cells of spleen and thymus from mice infected with Rauscher leukaemia virus were cultivated in vitro. A new cell type repeatedly grew out of this cell line. Electron-optically, RNA--viruses and DNA-viruses were found within the new lines, but there was no cell containing both viruses at the same time. According to experimental results in rats, the DNA virus is polyoma-like. The importance the presence of two different viruses within the same cell is discussed.", "contents": "[Presence of RNA-and DNA-tumor viruses within a cell line from mouse spleen and thymus (author's transl)]. Cells of spleen and thymus from mice infected with Rauscher leukaemia virus were cultivated in vitro. A new cell type repeatedly grew out of this cell line. Electron-optically, RNA--viruses and DNA-viruses were found within the new lines, but there was no cell containing both viruses at the same time. According to experimental results in rats, the DNA virus is polyoma-like. The importance the presence of two different viruses within the same cell is discussed."} {"id": "PMID:174520", "title": "Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus.", "content": "Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is progressively inactivated with increasing the time of UV-irradiation. The depressing effect of a TK- strain and the stimulating effect of a TK+ strain on superinfecting TK+ strains is UV-sensitive: after 6 minutes of UV-irradiation neither inhibition nor stimulation of TK induction by a superinfecting TK+ strain can be observed. Infection by long-term (20 minutes) UV-irradiated TK+ strains results in a depression of TK induction by a superinfecting TK+ virus. Long-term irradiation of the TK- virus does not show this effect. Cytosine-arabinoside has no effect on the mutual influence of TK induction by TK+ and TK-strains; the phenomenon of mutual depression therefore has to be considered an early process.", "contents": "Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus. Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is progressively inactivated with increasing the time of UV-irradiation. The depressing effect of a TK- strain and the stimulating effect of a TK+ strain on superinfecting TK+ strains is UV-sensitive: after 6 minutes of UV-irradiation neither inhibition nor stimulation of TK induction by a superinfecting TK+ strain can be observed. Infection by long-term (20 minutes) UV-irradiated TK+ strains results in a depression of TK induction by a superinfecting TK+ virus. Long-term irradiation of the TK- virus does not show this effect. Cytosine-arabinoside has no effect on the mutual influence of TK induction by TK+ and TK-strains; the phenomenon of mutual depression therefore has to be considered an early process."} {"id": "PMID:174521", "title": "Simian virus 40-chinese hamster kidney cell interaction. I. Relationship of chromosome changes to transformation.", "content": "After approximately 20 in vitro passages, Chinese hamster kidney (CHK) cell cultures transformed upon exposure to different strains of SV 40 can show a diploid modal chromosome number of 22 with chromosome counts exclusively or essentially in the diploid range (20-25). In primary culture and at the 5th-7th subculture, tumors produced in nude mice by such cells can display a diploid modal value of 22 chromosomes. Numerical chromosome variations and karyotype abnormalities observed in CHK cells transformed upon infection with SV 40, are apparently indistinguishable from those that can be observed in uninfected CHK cells undergoing \"spontaneous\"-transformation. These results indicate that polyploidization is not a necessary step either in the process of transformation or in that of tumorigenic conversion with SV 40.", "contents": "Simian virus 40-chinese hamster kidney cell interaction. I. Relationship of chromosome changes to transformation. After approximately 20 in vitro passages, Chinese hamster kidney (CHK) cell cultures transformed upon exposure to different strains of SV 40 can show a diploid modal chromosome number of 22 with chromosome counts exclusively or essentially in the diploid range (20-25). In primary culture and at the 5th-7th subculture, tumors produced in nude mice by such cells can display a diploid modal value of 22 chromosomes. Numerical chromosome variations and karyotype abnormalities observed in CHK cells transformed upon infection with SV 40, are apparently indistinguishable from those that can be observed in uninfected CHK cells undergoing \"spontaneous\"-transformation. These results indicate that polyploidization is not a necessary step either in the process of transformation or in that of tumorigenic conversion with SV 40."} {"id": "PMID:174522", "title": "Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections.", "content": "The isolation of swinepox virus in primary pig kidney cell cultures is reported. The differentiation from vaccinia virus was possible with challenge infections of convalescent pigs and the use of the agar gel diffusion precipitation (AGDP) test and immuno-electroosmophoresis (IEOP). Using both immune precipitation tests reactions of identity were obtained between the heterologous antigens of swinepox and vaccinia viruses. A total of 829 pig sera from the field were tested for precipitating antibodies with the IEOP. Antibodies were detected in 65 (=7.8 per cent) of these serum samples.", "contents": "Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. The isolation of swinepox virus in primary pig kidney cell cultures is reported. The differentiation from vaccinia virus was possible with challenge infections of convalescent pigs and the use of the agar gel diffusion precipitation (AGDP) test and immuno-electroosmophoresis (IEOP). Using both immune precipitation tests reactions of identity were obtained between the heterologous antigens of swinepox and vaccinia viruses. A total of 829 pig sera from the field were tested for precipitating antibodies with the IEOP. Antibodies were detected in 65 (=7.8 per cent) of these serum samples."} {"id": "PMID:174523", "title": "Ultrastructural aspects of experimental swinepox with special reference to inclusion bodies.", "content": "A light and electron microscopic study was performed on pox-like epidermal lesions in an experimentally infected pig. Light microscopical investigation of semithin sections revealed the presence of nuclear vacuoles and of different types of cytoplasmic inclusions. In electron microscopical studies large numbers of both immature and mature virus particles and the cytological changes indicative of pox virus infection were observed. Various types of intra-cytoplasmic inclusions -- i.e. fibrillar inclusions, crystalloid-containing dense inclusions, complex membraneous inclusions and dense homogeneous inclusions -- were encountered in addition to viroplasms and nuclear vacuoles. Because of the presence of vacuoles in nuclei of stratum spinosum cells the diagnosis swine pox by swinepox virus was most probable. These nuclear vacuoles have not been described in swine pox caused by vaccinia virus, the only other known cause of pox in swine.", "contents": "Ultrastructural aspects of experimental swinepox with special reference to inclusion bodies. A light and electron microscopic study was performed on pox-like epidermal lesions in an experimentally infected pig. Light microscopical investigation of semithin sections revealed the presence of nuclear vacuoles and of different types of cytoplasmic inclusions. In electron microscopical studies large numbers of both immature and mature virus particles and the cytological changes indicative of pox virus infection were observed. Various types of intra-cytoplasmic inclusions -- i.e. fibrillar inclusions, crystalloid-containing dense inclusions, complex membraneous inclusions and dense homogeneous inclusions -- were encountered in addition to viroplasms and nuclear vacuoles. Because of the presence of vacuoles in nuclei of stratum spinosum cells the diagnosis swine pox by swinepox virus was most probable. These nuclear vacuoles have not been described in swine pox caused by vaccinia virus, the only other known cause of pox in swine."} {"id": "PMID:174524", "title": "The polypeptide composition of avian infectious bronchitis virus.", "content": "Avian infectious bronchitis virus grown in ovo was purified by differential centrifugation and isopycnic sedimentation in density gradients. The purified virus was analysed by SDS polyacrylamide gel electrophoresis and found to comprise up to sixteen polypeptides, four of which were glycopeptides. Bromelain treatment of the particles removed three polypeptides and two glycopeptides.", "contents": "The polypeptide composition of avian infectious bronchitis virus. Avian infectious bronchitis virus grown in ovo was purified by differential centrifugation and isopycnic sedimentation in density gradients. The purified virus was analysed by SDS polyacrylamide gel electrophoresis and found to comprise up to sixteen polypeptides, four of which were glycopeptides. Bromelain treatment of the particles removed three polypeptides and two glycopeptides."} {"id": "PMID:174525", "title": "Purification of herpesvirus saimiri and properties of the viral DNA.", "content": "Conditions for growth, concentration, and purification of Herpesvirus saimiri were determined. Optimal yields of infectious Herpesvirus saimiri (HVS) were obtained from infected owl monkey kidney (OMK) cells grown at 32.5 degrees C in medium containing 10 per cent fetal calf serum. Forth-five percent of the initial infectious HVS was recovered after an 18-fold concentration using 8 per cent polyethylene glycol 6000 in the presence of 0.5 M NaCl. Polyethylene glycol concentrated HVS was purified in an isopycnic-linear Renografin gradient (1.0-1.3 g/cm3. Ninety-six percent of the infectivity was recovered in a single 1.16 g/cm3 density region. DNA extracted from purified HVS was resolved into two distinct density classes by CsCl equilibrium centrifugation (1.727 and 1.709 g/cm3). DNase treated HVA virions yield four DNA species with densities of 1.727, 1.718, 1.712, and 1.706 g/cm3 in CsCl centrifugation.", "contents": "Purification of herpesvirus saimiri and properties of the viral DNA. Conditions for growth, concentration, and purification of Herpesvirus saimiri were determined. Optimal yields of infectious Herpesvirus saimiri (HVS) were obtained from infected owl monkey kidney (OMK) cells grown at 32.5 degrees C in medium containing 10 per cent fetal calf serum. Forth-five percent of the initial infectious HVS was recovered after an 18-fold concentration using 8 per cent polyethylene glycol 6000 in the presence of 0.5 M NaCl. Polyethylene glycol concentrated HVS was purified in an isopycnic-linear Renografin gradient (1.0-1.3 g/cm3. Ninety-six percent of the infectivity was recovered in a single 1.16 g/cm3 density region. DNA extracted from purified HVS was resolved into two distinct density classes by CsCl equilibrium centrifugation (1.727 and 1.709 g/cm3). DNase treated HVA virions yield four DNA species with densities of 1.727, 1.718, 1.712, and 1.706 g/cm3 in CsCl centrifugation."} {"id": "PMID:174526", "title": "Polykaryocytosis induced by vesicular stomatitis virus infection in BHK-21 cells.", "content": "Cytopathological effects by vesicular stomatitis virus (VSV) infection were studied in several cell lines. Marked polykaryocyte formation was observed in monolayers of certain strains of BHK-21 cells infected with VSV. The BHK-21-KB cells were found to be the most susceptible to virus-induced cell fusion. This type of cell fusion was related to intracellular growth of the viruses, and strong cytolytic changes were found to occur following the development of large multinucleated giant cells. The cell-fusing activity was associated with the infectivity of VSV and was neutralized by anti-VSV immune serum. The viruses irradiated for 20 minutes or heated at 60 degrees C for 10 minutes lost completely both infectivity and cell-fusing activity. These experimental results indicate that virus replication was responsible for fusion of BHK cells.", "contents": "Polykaryocytosis induced by vesicular stomatitis virus infection in BHK-21 cells. Cytopathological effects by vesicular stomatitis virus (VSV) infection were studied in several cell lines. Marked polykaryocyte formation was observed in monolayers of certain strains of BHK-21 cells infected with VSV. The BHK-21-KB cells were found to be the most susceptible to virus-induced cell fusion. This type of cell fusion was related to intracellular growth of the viruses, and strong cytolytic changes were found to occur following the development of large multinucleated giant cells. The cell-fusing activity was associated with the infectivity of VSV and was neutralized by anti-VSV immune serum. The viruses irradiated for 20 minutes or heated at 60 degrees C for 10 minutes lost completely both infectivity and cell-fusing activity. These experimental results indicate that virus replication was responsible for fusion of BHK cells."} {"id": "PMID:174527", "title": "The influence of substances changing the intracellular concentration of cyclic adenosine 3'5'-monophosphate on interferon synthesis in chick embryo cell culture.", "content": "The influence of cyclic 3'5'-adenosine monophosphate (cAMP), adrenalin and theophylline on interferon synthesis induced by influenza B virus (Lee strain) in chick embryo cell cultures was studied. In 5-day-old cell culture, theophylline was shown to enhance the inhibiting effect of exogenous cAMP and adrenalin on interferon synthesis and in 1-day-old culture, on the contrary, to enhance interferon production whereas adrenaline under these conditions had no effect on interferon synthesis at all. In 5-day-old cultures the activity of adrenalin and theophylline was manifested when they were added to the maintenance medium not later than 4 hours postinfection, and was not associated with the influence on interferon inducer adsorption on to cells or on virus multiplication in sensitive systems. Treatment of cells with these substances had no effect on interferon release from the cells. In the concentration used, adrenalin and theophylline exerted no cytotoxic effect. Theophylline inhibited incorporation of 3H-uridine and 14C-leucine into the acid insoluble fraction of the infected cells in 1-day-old cultures, while in 5-day-old cultures this was observed only when adrenalin and theophylline were used together. It is suggested that endogenous cAMP is essential for control of interferon synthesis and that different cAMP levels in cells of different ages may be one of the causes of the varying potency for interferon synthesis in young and old cell cultures.", "contents": "The influence of substances changing the intracellular concentration of cyclic adenosine 3'5'-monophosphate on interferon synthesis in chick embryo cell culture. The influence of cyclic 3'5'-adenosine monophosphate (cAMP), adrenalin and theophylline on interferon synthesis induced by influenza B virus (Lee strain) in chick embryo cell cultures was studied. In 5-day-old cell culture, theophylline was shown to enhance the inhibiting effect of exogenous cAMP and adrenalin on interferon synthesis and in 1-day-old culture, on the contrary, to enhance interferon production whereas adrenaline under these conditions had no effect on interferon synthesis at all. In 5-day-old cultures the activity of adrenalin and theophylline was manifested when they were added to the maintenance medium not later than 4 hours postinfection, and was not associated with the influence on interferon inducer adsorption on to cells or on virus multiplication in sensitive systems. Treatment of cells with these substances had no effect on interferon release from the cells. In the concentration used, adrenalin and theophylline exerted no cytotoxic effect. Theophylline inhibited incorporation of 3H-uridine and 14C-leucine into the acid insoluble fraction of the infected cells in 1-day-old cultures, while in 5-day-old cultures this was observed only when adrenalin and theophylline were used together. It is suggested that endogenous cAMP is essential for control of interferon synthesis and that different cAMP levels in cells of different ages may be one of the causes of the varying potency for interferon synthesis in young and old cell cultures."} {"id": "PMID:174528", "title": "Immunoglobulins, antibodies and inhibitors of parainfluenza 3 virus in respiratory secretions of sheep.", "content": "Virus neutralising and haemagglutination inhibiting (HI) activities were monitored in the serum, nasal secretions and tracheo-bronchial secretions of lambs infected with Parainfluenza virus type 3 (PI3). HI activity was found in the secretions of both control and infected lambs, whereas neutralising antibody was found only in nasal secretions from infected lambs. Fractionation revealed that most of the HI activity in the secretions was due to a large molecular weight protein which also inhibited the haemagglutination (HA) of Parainfluenza virus type 1 (PI1) and type 2 (PI2) and Newcastle disease virus (NDV). This inhibitory activity was partially sensitive to receptor destroying enzyme (RDE). IgA antibodies specific for PI3 were also found in the respiratory secretions. However no increase in IgA levels was detected in the nasal secretions of the infected lambs. It is suggested that in certain reports non-specific inhibitors present in the nasal secretions of calves, may have been confused with PI3 specific IgA antibody.", "contents": "Immunoglobulins, antibodies and inhibitors of parainfluenza 3 virus in respiratory secretions of sheep. Virus neutralising and haemagglutination inhibiting (HI) activities were monitored in the serum, nasal secretions and tracheo-bronchial secretions of lambs infected with Parainfluenza virus type 3 (PI3). HI activity was found in the secretions of both control and infected lambs, whereas neutralising antibody was found only in nasal secretions from infected lambs. Fractionation revealed that most of the HI activity in the secretions was due to a large molecular weight protein which also inhibited the haemagglutination (HA) of Parainfluenza virus type 1 (PI1) and type 2 (PI2) and Newcastle disease virus (NDV). This inhibitory activity was partially sensitive to receptor destroying enzyme (RDE). IgA antibodies specific for PI3 were also found in the respiratory secretions. However no increase in IgA levels was detected in the nasal secretions of the infected lambs. It is suggested that in certain reports non-specific inhibitors present in the nasal secretions of calves, may have been confused with PI3 specific IgA antibody."} {"id": "PMID:174529", "title": "[Studies on the Relationship between immunity and the level of neutralizing antibodies in pigs vaccinated against foot-and-mouth disease (author's transl)].", "content": "The statistical relationship between the titers of neutralizing antibodies and the immunity of 706 pigs vaccinated against FMD was studied. This was done for each of four virus strains separately. Whereas no correlation between both test systems could be detected in case of the strains A5 Westerwald, C Detmold and O1Santander, a significant correlation was ascertained for the strain O1Kaufbeuren. Becuase of the different findings depending on the virus strain under study it was concluded that the antibody titer alone does not provide a useful measure for potency testing of FMD-vaccines for pigs.", "contents": "[Studies on the Relationship between immunity and the level of neutralizing antibodies in pigs vaccinated against foot-and-mouth disease (author's transl)]. The statistical relationship between the titers of neutralizing antibodies and the immunity of 706 pigs vaccinated against FMD was studied. This was done for each of four virus strains separately. Whereas no correlation between both test systems could be detected in case of the strains A5 Westerwald, C Detmold and O1Santander, a significant correlation was ascertained for the strain O1Kaufbeuren. Becuase of the different findings depending on the virus strain under study it was concluded that the antibody titer alone does not provide a useful measure for potency testing of FMD-vaccines for pigs."} {"id": "PMID:174530", "title": "Use of iodinated organic compounds for the density gradient centrifugation of viruses.", "content": "Use of Urografin and Conray for the equilibrium centrifugation of viruses is described. These pharmaceuticals, which consist of iodinated arylic compounds, reach densities of 1.6 g/cm3 and have low intrinsic viscosities. Poliovirus, Newcastle disease virus, and lymphocytic choriomeningitis virus were centrifuged to equilibrium in gradients made of these substances. Viral infectivities were not measurably affected, which is especially noteworthy in the case of the very labile lymphocytic choriomeningitis virus. Buoyant densities were found to be significantly lower than densities obtained with gradients made of CsCl and sucrose.", "contents": "Use of iodinated organic compounds for the density gradient centrifugation of viruses. Use of Urografin and Conray for the equilibrium centrifugation of viruses is described. These pharmaceuticals, which consist of iodinated arylic compounds, reach densities of 1.6 g/cm3 and have low intrinsic viscosities. Poliovirus, Newcastle disease virus, and lymphocytic choriomeningitis virus were centrifuged to equilibrium in gradients made of these substances. Viral infectivities were not measurably affected, which is especially noteworthy in the case of the very labile lymphocytic choriomeningitis virus. Buoyant densities were found to be significantly lower than densities obtained with gradients made of CsCl and sucrose."} {"id": "PMID:174531", "title": "Natural and experimental infections of Japanese tree sparrows with Japanese encephalitis virus.", "content": "20 to 37 per cent of wild Japanese tree sparrows had neutralizing antibodies to Japanese encephalitis virus (JEV). Sparrows free of antibodies were inoculated with 10,000 plaque-forming units of JEV. None of the birds became clinically ill. Virus could be detected in blood plasma during the first 3 days after inoculation but not thereafter. Neutralizing antibodies started to appear at 4 days after inoculation and the response was of variable duration, in some cases extending up to 200 days after inoculation.", "contents": "Natural and experimental infections of Japanese tree sparrows with Japanese encephalitis virus. 20 to 37 per cent of wild Japanese tree sparrows had neutralizing antibodies to Japanese encephalitis virus (JEV). Sparrows free of antibodies were inoculated with 10,000 plaque-forming units of JEV. None of the birds became clinically ill. Virus could be detected in blood plasma during the first 3 days after inoculation but not thereafter. Neutralizing antibodies started to appear at 4 days after inoculation and the response was of variable duration, in some cases extending up to 200 days after inoculation."} {"id": "PMID:174532", "title": "Inhibition of multiplication of parainfluenza 3 virus in prostaglandin-treated WISH cells.", "content": "Influence of prostaglandins E2 (PGE2) and F2alpha (PGF 2alpha) on multiplication of myxovirus parainfluenza 3 was investigated. At concentrations of 0.01--1 mug/ml prostaglandins had no direct cytotoxic effects. PGE2 and PGF2alpha inhibited multiplication of parainfluenza 3 virus at concentrations 0.1--10 mug/ml. The inhibitory effect was most pronounced when the prostaglandins were added to medium for the whole period of virus multiplication (48 hours) while little or no effect was found when prostaglandins were added before virus inoculation or for 2 hours after infection. It is suggested that prostaglandins exert an inhibitory effect on the replication phase of the virus by influencing the growth of the WISH cells.", "contents": "Inhibition of multiplication of parainfluenza 3 virus in prostaglandin-treated WISH cells. Influence of prostaglandins E2 (PGE2) and F2alpha (PGF 2alpha) on multiplication of myxovirus parainfluenza 3 was investigated. At concentrations of 0.01--1 mug/ml prostaglandins had no direct cytotoxic effects. PGE2 and PGF2alpha inhibited multiplication of parainfluenza 3 virus at concentrations 0.1--10 mug/ml. The inhibitory effect was most pronounced when the prostaglandins were added to medium for the whole period of virus multiplication (48 hours) while little or no effect was found when prostaglandins were added before virus inoculation or for 2 hours after infection. It is suggested that prostaglandins exert an inhibitory effect on the replication phase of the virus by influencing the growth of the WISH cells."} {"id": "PMID:174533", "title": "Triethyltin sulfate-induced neuropathy in rats. Electrophysiologic, morphologic, and biochemical studies.", "content": "Adult rats given high orally administered doses of triethyltin (TET) sulfate lost weight, developed hind limb wasting, and became paraplegic or quadriplegic within three weeks of intoxication. A 33% reduction in the motor nerve conduction velocity (MNCV) of the sciatic nerve in the absence of significant demyelination was observed. There was observed, however, intramyelinic edema formation and an increased number of axonal neurofilaments and neurotubules; changes that paralleled the decrease in MNCV during the period of intoxication. Although the animals became asymptomatic and the MNCV normalized within two to three weeks of discontinuing the TET intoxication, the intramyelinic vacuoles and the increased numbers of neurofilaments and neurotubules persisted.", "contents": "Triethyltin sulfate-induced neuropathy in rats. Electrophysiologic, morphologic, and biochemical studies. Adult rats given high orally administered doses of triethyltin (TET) sulfate lost weight, developed hind limb wasting, and became paraplegic or quadriplegic within three weeks of intoxication. A 33% reduction in the motor nerve conduction velocity (MNCV) of the sciatic nerve in the absence of significant demyelination was observed. There was observed, however, intramyelinic edema formation and an increased number of axonal neurofilaments and neurotubules; changes that paralleled the decrease in MNCV during the period of intoxication. Although the animals became asymptomatic and the MNCV normalized within two to three weeks of discontinuing the TET intoxication, the intramyelinic vacuoles and the increased numbers of neurofilaments and neurotubules persisted."} {"id": "PMID:174534", "title": "Experimental parainfluenza type 1 virus-induced encephalopathy in adult mice. Pathogenesis of chronic degenerative changes in the CNS.", "content": "The pathogenicity of the 6/94 strain of parainfluenza type 1 virus, originally isolated from multiple sclerosis brain, was studied in adult mouse brains. Intracerebral inoculation of the virus caused mononuclear cell infiltration in the form of perivascular cuffing and a diffuse exudation into the parenchymal tissue, preferentially in cerebral white matter, that resulted in marked degeneration over a 90-day observation period. Immunofluorescent staining revealed viral antigen in the ependymal lining cells only during the first seven days after infection. No correlation was found between the severity of the brain lesions and the level of circulating antiviral antibody, preexisting or newly produced.", "contents": "Experimental parainfluenza type 1 virus-induced encephalopathy in adult mice. Pathogenesis of chronic degenerative changes in the CNS. The pathogenicity of the 6/94 strain of parainfluenza type 1 virus, originally isolated from multiple sclerosis brain, was studied in adult mouse brains. Intracerebral inoculation of the virus caused mononuclear cell infiltration in the form of perivascular cuffing and a diffuse exudation into the parenchymal tissue, preferentially in cerebral white matter, that resulted in marked degeneration over a 90-day observation period. Immunofluorescent staining revealed viral antigen in the ependymal lining cells only during the first seven days after infection. No correlation was found between the severity of the brain lesions and the level of circulating antiviral antibody, preexisting or newly produced."} {"id": "PMID:174535", "title": "Lesions produced by human herpesviruses 1 and 2. Morphologic features in rabbit corneal epithelium.", "content": "The morphologic features of corneal lesions produced in rabbits by human herpesviruses, types 1 and 2 (HH1 and HH2), were studied using light and electron microscopic techniques. Also, healing lesions produced by the HH1 virus and treated by idoxuridine were similarly investigated. Scanning electron micrographs showed that although the morphology of HH1 and HH2 lesions was similar in most respects. HH2 lesions typically were raised, whereas the edges of HH1 lesions were not elevated above the corneal surface. In both HH1 and HH2 lesions, infected epithelial cells first separated from neighboring cells, then became globular, and finally were removed, leaving a central excavation. During healing of HH1 lesions, normal epithelial cells invaded the central crater from all sides to cover damaged cells and reconstitute the epithelial surface.", "contents": "Lesions produced by human herpesviruses 1 and 2. Morphologic features in rabbit corneal epithelium. The morphologic features of corneal lesions produced in rabbits by human herpesviruses, types 1 and 2 (HH1 and HH2), were studied using light and electron microscopic techniques. Also, healing lesions produced by the HH1 virus and treated by idoxuridine were similarly investigated. Scanning electron micrographs showed that although the morphology of HH1 and HH2 lesions was similar in most respects. HH2 lesions typically were raised, whereas the edges of HH1 lesions were not elevated above the corneal surface. In both HH1 and HH2 lesions, infected epithelial cells first separated from neighboring cells, then became globular, and finally were removed, leaving a central excavation. During healing of HH1 lesions, normal epithelial cells invaded the central crater from all sides to cover damaged cells and reconstitute the epithelial surface."} {"id": "PMID:174536", "title": "Herpesvirus hominis encephalitis and retinitis.", "content": "A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina.", "contents": "Herpesvirus hominis encephalitis and retinitis. A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina."} {"id": "PMID:174537", "title": "[Problems of the electric response audiometry (ERA) during the natural and artificial sleep (author's transl)].", "content": "The investigators carried out threshold determinations on 16 children and 6 adults in wakefulness, under general anaesthesia (we used chloral hydrate anaesthesia) and in sleep (stage II-III and stage REM). Falling asleep (stage I and initial stage of anaesthesia respectively) the latencies of the individual components of the acoustically evoked potentials are prolonged in mean of 30 msec. Simultaneously the amplitude of N1 significantly decreases and N2 becomes a prominent point (Fig. 1). The generation mechanisms of wave N2 are obviously different from those of wave N1. Its input-output curve takes a very steep course (Fig. 5) and the shortening of latencies increases with growing intensity of stimulus too (Fig. 4). Amplitude histogrammes demonstrated the dependency of the form of the acoustically evoked potential on the degree of synchronisation of EEG activity. While in the case of desynchronisation N1 appears more markedly, N2 does in the case of synchronisation. The mean deviation of the ERA threshold totals plus 3.8 +/- 6.9 dB (n = 41) under chloral hydrate anaesthesia, plus 4.9 +/- 6.7 dB (n = 37) in natural sleep in contrast to the wakefulness. With a 99% confidence there occur confidence intervals ranging from + 1 to + 7 dB and from +2 to +8 dB respectively. In identifying the threshold potentials error I (existing potential not recognized) occurred in 15-20%, error II (random wave seen as potential) in 20% of these studies. All these experiments showed significant lower variances for the latencies compared with variancies of amplitudes. The variance of amplitudes is smallest in children (Table 1) under general anaesthesia as well as in adults in wakefulness (Table 2). For the practical performance of ERA chloral hydrate is recommended for studies on children. A uniform EEG-state as well as a uniform depth of sleep are basic conditions for ERA during sleep, sedation or under anaesthesia. These conditions must constantly be controlled by EEG, EOG and EMG.", "contents": "[Problems of the electric response audiometry (ERA) during the natural and artificial sleep (author's transl)]. The investigators carried out threshold determinations on 16 children and 6 adults in wakefulness, under general anaesthesia (we used chloral hydrate anaesthesia) and in sleep (stage II-III and stage REM). Falling asleep (stage I and initial stage of anaesthesia respectively) the latencies of the individual components of the acoustically evoked potentials are prolonged in mean of 30 msec. Simultaneously the amplitude of N1 significantly decreases and N2 becomes a prominent point (Fig. 1). The generation mechanisms of wave N2 are obviously different from those of wave N1. Its input-output curve takes a very steep course (Fig. 5) and the shortening of latencies increases with growing intensity of stimulus too (Fig. 4). Amplitude histogrammes demonstrated the dependency of the form of the acoustically evoked potential on the degree of synchronisation of EEG activity. While in the case of desynchronisation N1 appears more markedly, N2 does in the case of synchronisation. The mean deviation of the ERA threshold totals plus 3.8 +/- 6.9 dB (n = 41) under chloral hydrate anaesthesia, plus 4.9 +/- 6.7 dB (n = 37) in natural sleep in contrast to the wakefulness. With a 99% confidence there occur confidence intervals ranging from + 1 to + 7 dB and from +2 to +8 dB respectively. In identifying the threshold potentials error I (existing potential not recognized) occurred in 15-20%, error II (random wave seen as potential) in 20% of these studies. All these experiments showed significant lower variances for the latencies compared with variancies of amplitudes. The variance of amplitudes is smallest in children (Table 1) under general anaesthesia as well as in adults in wakefulness (Table 2). For the practical performance of ERA chloral hydrate is recommended for studies on children. A uniform EEG-state as well as a uniform depth of sleep are basic conditions for ERA during sleep, sedation or under anaesthesia. These conditions must constantly be controlled by EEG, EOG and EMG."} {"id": "PMID:174538", "title": "Galactose metabolism in relation to cataract formation in marsupials.", "content": "Erythrocytic galactokinase and/or galactose-1-phosphate uridyl transferase activity were low in many species of marsupials. However, cataract formation was observed only in pouch-young members of these species when reared on cow's milk. The galactose tolerance of young kangaroos was found to be greatly impaired, but improved rapidly and markedly at the stage of which the definitive structure of the ruminant type of stomach as in adults is formed. The combination of high absorption of galactose and low levels of galactokinase and/or transferase thus appears to determine the predisposition of pouch-young marsupials to galactose cataractogenesis.", "contents": "Galactose metabolism in relation to cataract formation in marsupials. Erythrocytic galactokinase and/or galactose-1-phosphate uridyl transferase activity were low in many species of marsupials. However, cataract formation was observed only in pouch-young members of these species when reared on cow's milk. The galactose tolerance of young kangaroos was found to be greatly impaired, but improved rapidly and markedly at the stage of which the definitive structure of the ruminant type of stomach as in adults is formed. The combination of high absorption of galactose and low levels of galactokinase and/or transferase thus appears to determine the predisposition of pouch-young marsupials to galactose cataractogenesis."} {"id": "PMID:174539", "title": "Prolonged control of hypoglycaemia by L-asparaginase in islet cell carcinoma producing insulin and gastrin.", "content": "L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin.", "contents": "Prolonged control of hypoglycaemia by L-asparaginase in islet cell carcinoma producing insulin and gastrin. L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin."} {"id": "PMID:174540", "title": "Insulinoma: aids to management.", "content": "Three cases of insulinoma seen in the past few months are reported in order to highlight recent advances in the management of this condition. These advances include serum insulin level determinations to correlate with blood sugar levels; selective arteriography as a means of localizing a tumour; and the monitoring of blood sugar levels during surgery.", "contents": "Insulinoma: aids to management. Three cases of insulinoma seen in the past few months are reported in order to highlight recent advances in the management of this condition. These advances include serum insulin level determinations to correlate with blood sugar levels; selective arteriography as a means of localizing a tumour; and the monitoring of blood sugar levels during surgery."} {"id": "PMID:174543", "title": "A study of the interrelationship between the triacylglycerol and protein components of very-low-density lipoproteins using the perfused rat liver.", "content": "High and low rates of very-low-density-lipoprotein triacylglycerol release from the perfused rat liver were achieved by using livers taken respectively from animals that had been given fructose for 48h or from animals that had been starved for 18h. 2. The higher rates of very-low-density-lipoprotein triacylglycerol release by the livers of the fructose-fed rats were associated with higher rates of very-low-density-lipoprotein protein release. 3. When the livers were perfused in the presence of [3H]leucine, radioactivity was incorporated into the very-low-density-lipoprotein apoproteins. The higher rates of very-low-density-lipoprotein triacylgycerol and protein release by the livers of fructose-fed rats were associated with a greater total incorporation of radioactivity into those apoproteins that entered the running gel during polyacrylamide-gel electrophoresis. However, the distribution of radioactivity among the various apoproteins was not significantly changed by the dietary treatments used.", "contents": "A study of the interrelationship between the triacylglycerol and protein components of very-low-density lipoproteins using the perfused rat liver. High and low rates of very-low-density-lipoprotein triacylglycerol release from the perfused rat liver were achieved by using livers taken respectively from animals that had been given fructose for 48h or from animals that had been starved for 18h. 2. The higher rates of very-low-density-lipoprotein triacylglycerol release by the livers of the fructose-fed rats were associated with higher rates of very-low-density-lipoprotein protein release. 3. When the livers were perfused in the presence of [3H]leucine, radioactivity was incorporated into the very-low-density-lipoprotein apoproteins. The higher rates of very-low-density-lipoprotein triacylgycerol and protein release by the livers of fructose-fed rats were associated with a greater total incorporation of radioactivity into those apoproteins that entered the running gel during polyacrylamide-gel electrophoresis. However, the distribution of radioactivity among the various apoproteins was not significantly changed by the dietary treatments used."} {"id": "PMID:174544", "title": "A comparison of the regulation of pyruvate dehydrogenase in mitochondria from rat brain and liver.", "content": "The total activity of pyruvate dehydrogenase in mitochondria isolated from rat brain and liver was 53.5 and 14.2nmol/min per mg of protein respectively. Pyruvate dehydrogenase in liver mitochondria incubated for 4 min at 37 degrees C with no additions was 30% in the active form and this activity increased with longer incubations until it was completely in the active form after 20 min. Brain mitochondrial pyruvate dehydrogenase activity was initially high and did not increase with addition of Mg2+ plus Ca2+ or partially purified pyruvate dehydrogenase phosphatase or with longer incubations. The proportion of pyruvate dehydrogenase in the active form in both brain and liver mitochondria changed inversely with changes in mitochondrial energy charge, whereas total pyruvate dehydrogenase did not change. The chelators citrate, isocitrate, EDTA, ethanedioxybis(ethylamine)tetra-acetic acid and Ruthenium Red each lowered pyruvate dehydrogenase activity in brain mitochondria, but only citrate and isocitrate did so in liver mitochondria. These chelators did not affect the energy charge of the mitochondria. Mg2+ plus Ca2+ reversed the pyruvate dehydrogenase inactivation in liver, but not brain, mitochondria. The regulation of the activation-inactivation of pyruvate dehydrogenase in mitochondria from rat brain and liver with respect to energy charge is similar and may be at least partially regulated by this parameter, and the effects of chelators differ in the two types of mitochondria.", "contents": "A comparison of the regulation of pyruvate dehydrogenase in mitochondria from rat brain and liver. The total activity of pyruvate dehydrogenase in mitochondria isolated from rat brain and liver was 53.5 and 14.2nmol/min per mg of protein respectively. Pyruvate dehydrogenase in liver mitochondria incubated for 4 min at 37 degrees C with no additions was 30% in the active form and this activity increased with longer incubations until it was completely in the active form after 20 min. Brain mitochondrial pyruvate dehydrogenase activity was initially high and did not increase with addition of Mg2+ plus Ca2+ or partially purified pyruvate dehydrogenase phosphatase or with longer incubations. The proportion of pyruvate dehydrogenase in the active form in both brain and liver mitochondria changed inversely with changes in mitochondrial energy charge, whereas total pyruvate dehydrogenase did not change. The chelators citrate, isocitrate, EDTA, ethanedioxybis(ethylamine)tetra-acetic acid and Ruthenium Red each lowered pyruvate dehydrogenase activity in brain mitochondria, but only citrate and isocitrate did so in liver mitochondria. These chelators did not affect the energy charge of the mitochondria. Mg2+ plus Ca2+ reversed the pyruvate dehydrogenase inactivation in liver, but not brain, mitochondria. The regulation of the activation-inactivation of pyruvate dehydrogenase in mitochondria from rat brain and liver with respect to energy charge is similar and may be at least partially regulated by this parameter, and the effects of chelators differ in the two types of mitochondria."} {"id": "PMID:174545", "title": "Effect of protein-synthesis inhibitors on testosterone production in rat testis interstitial tissue and Leydig-cell preparations.", "content": "Luteinizing-hormone-stimulated testosterone biosynthesis was inhibited by cycloheximide during incubation of rat testis intersitial tissue in vitro and also by puromycin and cycloheximide during incubation of Leydig-cell preparations, but not by chloramphenicol. These results suggest that a protein regualtor(s) formed by cytoplasmic protein synthesis is involved in steroidogenesis in the rat testis. The specific effect of cycloheximide and puromycin on protein synthesis rather than on other non-specific processes is suggested by the inhibition of protein synthesis and steroidogenesis with different doses of the inhibitors and the lack of effect of cycloheximide on luteinizing-hormone-induced adenosine 3':5'-cyclic monophosphate production. Stimulation of testosterone production by luteinizing hormone during superfusion of interstitial tissue was detectable within 10-20 min and reached a maximum of 120 min, and thereafter slowly decreased. Cycloheximide added at maximum steroid production caused a rapid decrease in testosterone synthesis which followed first-order kinetics (half-life 13 min), thus indicating that the protein regulator(s) has a short half-life. No effect of cycloheximide, puromycin or chloramphenicol on testosterone production in the absence of added luteinizing hormone was found, suggesting that the basal production of testosterone is independent of protein synthesis.", "contents": "Effect of protein-synthesis inhibitors on testosterone production in rat testis interstitial tissue and Leydig-cell preparations. Luteinizing-hormone-stimulated testosterone biosynthesis was inhibited by cycloheximide during incubation of rat testis intersitial tissue in vitro and also by puromycin and cycloheximide during incubation of Leydig-cell preparations, but not by chloramphenicol. These results suggest that a protein regualtor(s) formed by cytoplasmic protein synthesis is involved in steroidogenesis in the rat testis. The specific effect of cycloheximide and puromycin on protein synthesis rather than on other non-specific processes is suggested by the inhibition of protein synthesis and steroidogenesis with different doses of the inhibitors and the lack of effect of cycloheximide on luteinizing-hormone-induced adenosine 3':5'-cyclic monophosphate production. Stimulation of testosterone production by luteinizing hormone during superfusion of interstitial tissue was detectable within 10-20 min and reached a maximum of 120 min, and thereafter slowly decreased. Cycloheximide added at maximum steroid production caused a rapid decrease in testosterone synthesis which followed first-order kinetics (half-life 13 min), thus indicating that the protein regulator(s) has a short half-life. No effect of cycloheximide, puromycin or chloramphenicol on testosterone production in the absence of added luteinizing hormone was found, suggesting that the basal production of testosterone is independent of protein synthesis."} {"id": "PMID:174546", "title": "The maturation of the inner membrane of foetal rat liver mitochondria.", "content": "A new method was devised for the isolation of foetal and neonatal rat lvier mitochondria, giving higher yields than conventional methods. 2. During development from the perinatal period to the mature adult, the ratio of cytochrome oxidase/succinate-cytochrome c reductase changes. 3. The inner mitochondrial membrane of foetal liver mitochondria possesses virtually no osmotic activity; the permeability to sucrose decreases with increasing developmental age. 4. Foetal rat liver mitochondria possess only marginal respiratory control and do not maintain Ca2+-induced respiration; they also swell in respiratory-control medium in the absence of substrate. ATP enhances respiratory control and prevents swelling, adenylyl imidodiphosphate, ATP+atractyloside enhance the R.C.I. (respiratory control index), Ca2+-induced respiratory control and prevent swelling, whereas GTP and low concentrations of ADP have none of these actions. It is concluded that the effect of ATP depends on steric interaction with the inner mitochondrial membrane. 5. When 1-day pre-partum foetuses are obtained by Caesarean section and maintained in a Humidicrib for 90 min, mitochondrial maturation is \"triggered\", so that their R.C.I. is enhanced and no ATP is required to support Ca2+-dependent respiratory control or to inhibit mitochondrial swelling. 6. It is concluded that foetal rat liver mitochondria in utero do not respire, although they are capable of oxidative phosphorylation in spite of their low R.C.I. The different environmental conditions which the neonatal rat encounters ex utero enable the hepatic mitochondria to produce ATP, which interacts with the inner mitochondrial membrane to enhance oxidative phosphorylation by an autocatalytic mechanism.", "contents": "The maturation of the inner membrane of foetal rat liver mitochondria. A new method was devised for the isolation of foetal and neonatal rat lvier mitochondria, giving higher yields than conventional methods. 2. During development from the perinatal period to the mature adult, the ratio of cytochrome oxidase/succinate-cytochrome c reductase changes. 3. The inner mitochondrial membrane of foetal liver mitochondria possesses virtually no osmotic activity; the permeability to sucrose decreases with increasing developmental age. 4. Foetal rat liver mitochondria possess only marginal respiratory control and do not maintain Ca2+-induced respiration; they also swell in respiratory-control medium in the absence of substrate. ATP enhances respiratory control and prevents swelling, adenylyl imidodiphosphate, ATP+atractyloside enhance the R.C.I. (respiratory control index), Ca2+-induced respiratory control and prevent swelling, whereas GTP and low concentrations of ADP have none of these actions. It is concluded that the effect of ATP depends on steric interaction with the inner mitochondrial membrane. 5. When 1-day pre-partum foetuses are obtained by Caesarean section and maintained in a Humidicrib for 90 min, mitochondrial maturation is \"triggered\", so that their R.C.I. is enhanced and no ATP is required to support Ca2+-dependent respiratory control or to inhibit mitochondrial swelling. 6. It is concluded that foetal rat liver mitochondria in utero do not respire, although they are capable of oxidative phosphorylation in spite of their low R.C.I. The different environmental conditions which the neonatal rat encounters ex utero enable the hepatic mitochondria to produce ATP, which interacts with the inner mitochondrial membrane to enhance oxidative phosphorylation by an autocatalytic mechanism."} {"id": "PMID:174547", "title": "Conversion of thyroxine into tri-iodothyronine by rat liver homogenate.", "content": "By using a highly specific radioimmunoassay the formation of tri-iodothyronine by the deiodination of thyroxine was studied in rat liver homogenate. Several observations suggest that the reaction observed is enzymic in nature. Pre-heating the homogenate for 30 min at 56 degrees C completely abolished conversion of thyroxine into tri-iodothyronine; the component of rat liver homogenate responsible could be saturated with substrate; iodotyrosines displayed competitive activity. Between 0 degrees and 37 degrees C, the tri-iodothyronine-production rate was positively correlated with incubation temperature. The addition of NAD+ enhanced conversion into tri-iodothyronine, which suggests that an oxidative mechanism is involved. 5-Propyl-2-thiouracil and 6-propyl-2-thiouracil, both known to prevent deiodination in vivo, greatly decreased the deiodiantion activity of rat liver homogenate.", "contents": "Conversion of thyroxine into tri-iodothyronine by rat liver homogenate. By using a highly specific radioimmunoassay the formation of tri-iodothyronine by the deiodination of thyroxine was studied in rat liver homogenate. Several observations suggest that the reaction observed is enzymic in nature. Pre-heating the homogenate for 30 min at 56 degrees C completely abolished conversion of thyroxine into tri-iodothyronine; the component of rat liver homogenate responsible could be saturated with substrate; iodotyrosines displayed competitive activity. Between 0 degrees and 37 degrees C, the tri-iodothyronine-production rate was positively correlated with incubation temperature. The addition of NAD+ enhanced conversion into tri-iodothyronine, which suggests that an oxidative mechanism is involved. 5-Propyl-2-thiouracil and 6-propyl-2-thiouracil, both known to prevent deiodination in vivo, greatly decreased the deiodiantion activity of rat liver homogenate."} {"id": "PMID:174548", "title": "Phosphomonoesterase hydrolysis of polyphosphoinositides in rat kidney: Properties and subcellular localization of the enzyme system.", "content": "Tthe properties of diphosphoinositide and triphosphoinositide phosphatases from rat kidney homogenate were studied in an assay system in which non-specific phosphatase activity was eliminated. The enzymes were not completely metal-ion dependent and were activated by Mg2+. The detergent sodium deoxycholate, Triton X-100 and Cutscum inhibited the reaction; cetyltrimethylammonium bromide only activated when added with the subtrates and in the presence Mg2+. Both enzymes had a pH optimum of 7.5. Ca2+ and Li+ both activated triphosphoinositide phosphatase, but Ca2+ inhibited and L+ had little effect on diphosphoinositide phosphatase. Cyclic AMP had no effect on either enzyme. The enzymes were three times more active in kidney cortex than in the medulla. On subcellular fractionation of kidney-cortex homogenates by differential and density-gradient centrifugation, the distribution of the enzymes resembled that of thiamin pyrophosphatase (assayed in the absence of ATP), suggesting localization in the Golgi complex. However, the distribution differed from that of the liver Golgimarker galactosyltransferase. Activities of both diphosphoinositide and triphosphoinositide phosphatases and thiamin pyrophosphatase were low in purified brush-border fragments. Further experiments indicate that at least part of the phosphatase activity is soluble.", "contents": "Phosphomonoesterase hydrolysis of polyphosphoinositides in rat kidney: Properties and subcellular localization of the enzyme system. Tthe properties of diphosphoinositide and triphosphoinositide phosphatases from rat kidney homogenate were studied in an assay system in which non-specific phosphatase activity was eliminated. The enzymes were not completely metal-ion dependent and were activated by Mg2+. The detergent sodium deoxycholate, Triton X-100 and Cutscum inhibited the reaction; cetyltrimethylammonium bromide only activated when added with the subtrates and in the presence Mg2+. Both enzymes had a pH optimum of 7.5. Ca2+ and Li+ both activated triphosphoinositide phosphatase, but Ca2+ inhibited and L+ had little effect on diphosphoinositide phosphatase. Cyclic AMP had no effect on either enzyme. The enzymes were three times more active in kidney cortex than in the medulla. On subcellular fractionation of kidney-cortex homogenates by differential and density-gradient centrifugation, the distribution of the enzymes resembled that of thiamin pyrophosphatase (assayed in the absence of ATP), suggesting localization in the Golgi complex. However, the distribution differed from that of the liver Golgimarker galactosyltransferase. Activities of both diphosphoinositide and triphosphoinositide phosphatases and thiamin pyrophosphatase were low in purified brush-border fragments. Further experiments indicate that at least part of the phosphatase activity is soluble."} {"id": "PMID:174549", "title": "Poly(glucosylglycerol phosphate) teichoic acid in the walls of Bacillus stearothermophilus B65.", "content": "1. Walls of Bacillus stearothermophilus B65 contain a glycerol teichoic acid in which repeating structures consisting of 1-O-alpha-D-glucopyranosylglycerol phosphate are held together by phosphodiester linkage between the glycerol and glucose moieties of adjacent units. 2. The walls are not agglutinated on incubation with concanavalin A, nor does the isolated teichoic acid form a precipitate with this lectin. 3. No evidence was obtained of the presence of the glucosylated (1 leads to 2)-poly(glycerol phosphate) teichoic acid which has previously been reported to occur in walls of this bacterium.", "contents": "Poly(glucosylglycerol phosphate) teichoic acid in the walls of Bacillus stearothermophilus B65. 1. Walls of Bacillus stearothermophilus B65 contain a glycerol teichoic acid in which repeating structures consisting of 1-O-alpha-D-glucopyranosylglycerol phosphate are held together by phosphodiester linkage between the glycerol and glucose moieties of adjacent units. 2. The walls are not agglutinated on incubation with concanavalin A, nor does the isolated teichoic acid form a precipitate with this lectin. 3. No evidence was obtained of the presence of the glucosylated (1 leads to 2)-poly(glycerol phosphate) teichoic acid which has previously been reported to occur in walls of this bacterium."} {"id": "PMID:174550", "title": "A rapid NAD+-linked assay for microsomal uridine diphosphate glucuronyltransferase of rat liver and some observations on substrate specificity of the enzyme.", "content": "1. A new and rapid continuous assay of rat liver microsomal UDP-glucuronyltransferase (EC 2.4.1.17) has been developed. It is based on measurement of UDP production from UDP-glucuronate during the glucuronidation reaction; UDP production was continuously measured by coupling it to the conversion of NADH into NAD+ through pyruvate kinase and lactate dehydrogenase. This assay is independent of the acceptor substrate used; several findings confirm its applicability. 2. The glucuronidation rate of a series of phenol derivatives was determined with this assay, by using a Triton X-100-activated microsomal preparation as enzyme source. Conjugation of a series of nitrophenol derivatives was also investigated by the 'classical' assay (measurement of disappearance of the yellow colour of the nitrophenol during glucuronidation). The substrate with the highest conversion rate was 3-methyl-2-nitrophenol. 3. Both electron releasing and electron withdrawing ring substituents increased the glucuronidation rate of the phenol derivatives, as compared with phenol. 4. Lipid solubility seems important for determining the conversion rate: poorly lipid-soluble substrates were glucuronidated only at a low rate and high lipid solubility seems to be a prerequisite for high conversion rate. Glucuronidation of poorly lipid-soluble compounds may be limited by diffusion. 5. The consequences of these findings for the interpretation of studies on heterogeneity of the enzyme are discussed.", "contents": "A rapid NAD+-linked assay for microsomal uridine diphosphate glucuronyltransferase of rat liver and some observations on substrate specificity of the enzyme. 1. A new and rapid continuous assay of rat liver microsomal UDP-glucuronyltransferase (EC 2.4.1.17) has been developed. It is based on measurement of UDP production from UDP-glucuronate during the glucuronidation reaction; UDP production was continuously measured by coupling it to the conversion of NADH into NAD+ through pyruvate kinase and lactate dehydrogenase. This assay is independent of the acceptor substrate used; several findings confirm its applicability. 2. The glucuronidation rate of a series of phenol derivatives was determined with this assay, by using a Triton X-100-activated microsomal preparation as enzyme source. Conjugation of a series of nitrophenol derivatives was also investigated by the 'classical' assay (measurement of disappearance of the yellow colour of the nitrophenol during glucuronidation). The substrate with the highest conversion rate was 3-methyl-2-nitrophenol. 3. Both electron releasing and electron withdrawing ring substituents increased the glucuronidation rate of the phenol derivatives, as compared with phenol. 4. Lipid solubility seems important for determining the conversion rate: poorly lipid-soluble substrates were glucuronidated only at a low rate and high lipid solubility seems to be a prerequisite for high conversion rate. Glucuronidation of poorly lipid-soluble compounds may be limited by diffusion. 5. The consequences of these findings for the interpretation of studies on heterogeneity of the enzyme are discussed."} {"id": "PMID:174551", "title": "Proteoglycans of hyaline cartilage: Electron-microscopic studies on isolated molecules.", "content": "Proteoglycan monomers from guinea-pig costal cartilage, bovine nasal and bovine tracheal cartilage were observed in the electron microscope after being spread in a monomolecular layer with cytochrome c. The proteoglycan molecule appeared as an extended central core filament to which side-chain filaments were attached at various intervals. The molecules from the three sources displayed great ultrastructural similarities. On average, the core filament was about 290 nm long, there were about 25 side-chain filaments per core filament, the side-chain filaments were about 45 nm long, and the distance between the attachment points of the side-chain filaments to the core filament was about 11 nm. With regard to the overall size of the molecules, no evidence of distinct subpopulations was obtained. Good correlation was found between ultrastructural data for the proteoglycan molecules and chemical data obtained by enzyme digestions and gel chromatography. Together these data strongly support the interpretation of the electron-microscopic pictures as indicating a central filament corresponding to the protein core and side-chain filaments corresponding to the chondroitin sulphate chain clusters of the proteoglycan monomers.", "contents": "Proteoglycans of hyaline cartilage: Electron-microscopic studies on isolated molecules. Proteoglycan monomers from guinea-pig costal cartilage, bovine nasal and bovine tracheal cartilage were observed in the electron microscope after being spread in a monomolecular layer with cytochrome c. The proteoglycan molecule appeared as an extended central core filament to which side-chain filaments were attached at various intervals. The molecules from the three sources displayed great ultrastructural similarities. On average, the core filament was about 290 nm long, there were about 25 side-chain filaments per core filament, the side-chain filaments were about 45 nm long, and the distance between the attachment points of the side-chain filaments to the core filament was about 11 nm. With regard to the overall size of the molecules, no evidence of distinct subpopulations was obtained. Good correlation was found between ultrastructural data for the proteoglycan molecules and chemical data obtained by enzyme digestions and gel chromatography. Together these data strongly support the interpretation of the electron-microscopic pictures as indicating a central filament corresponding to the protein core and side-chain filaments corresponding to the chondroitin sulphate chain clusters of the proteoglycan monomers."} {"id": "PMID:174552", "title": "An improved method for purifying sialidase.", "content": "An adsorbent specific for sialidase (EC 3.2.1.18) was prepared by coupling a glycoprotein containing glycosidically linked sialic acid to Sepharose. This adsorbent does not display the non-specific adsorption that occurs in previously reported methods.", "contents": "An improved method for purifying sialidase. An adsorbent specific for sialidase (EC 3.2.1.18) was prepared by coupling a glycoprotein containing glycosidically linked sialic acid to Sepharose. This adsorbent does not display the non-specific adsorption that occurs in previously reported methods."} {"id": "PMID:174553", "title": "A temperature-jump study of the reaction between azurin and cytochrome c oxidase from Pseudomonas aeruginosa.", "content": "The electron-transfer reaction between azurin and the cytochrome oxidase from Pseudomonas aeruginosa was investigated by temperature-jump relaxation in the absence of O2 and in the presence of CO. The results show that: (i) reduced azurin exists in two forms in equilibrium, only one of which is capable of exchanging electrons with the Pseudomonas cytochrome oxidase, in agreement with M. T. Wilson, C. Greenwood, M. Brunori & E. Antonini (1975) (Biochem. J. 145, 449-457); (ii) the electron transfer between azurin and Pseudomonas cytochrome oxidase occurs within a molecular complex of the two proteins; this internal transfer becomes rate-limiting at high reagent concentrations.", "contents": "A temperature-jump study of the reaction between azurin and cytochrome c oxidase from Pseudomonas aeruginosa. The electron-transfer reaction between azurin and the cytochrome oxidase from Pseudomonas aeruginosa was investigated by temperature-jump relaxation in the absence of O2 and in the presence of CO. The results show that: (i) reduced azurin exists in two forms in equilibrium, only one of which is capable of exchanging electrons with the Pseudomonas cytochrome oxidase, in agreement with M. T. Wilson, C. Greenwood, M. Brunori & E. Antonini (1975) (Biochem. J. 145, 449-457); (ii) the electron transfer between azurin and Pseudomonas cytochrome oxidase occurs within a molecular complex of the two proteins; this internal transfer becomes rate-limiting at high reagent concentrations."} {"id": "PMID:174554", "title": "Adenosine 3':5'-cyclic monophosphate-dependent and plasma-membrane-associated protein kinase(s) from bovine corpus luteum.", "content": "Plasma-membrane fractions FI and FII isolated from bovine corpus luteum by discontinuous sucrose-density-gradient centrifugation, at sucrose-density interfaces of 1.14/1.16 and 1.16/1.18 respectively, contained membrane-associated protein kinases that phosphorylated both the structural proteins of membranes as well as exogenously added protein substrates. Both fractions were characterized with respect to endogenous and exogenous protein substrate specificity, pH-dependence, effect of bivalent metal ions and sensitivity toward cyclic nucleotides. These membrane-associated kinases showed an optimum pH of 6.0 and had an absolute requirement for bivalent metal ions such as Mg2+, Mn2+, or Co2+ that cannot be replaced by Ca2+. Both the activities were stimulated two- to four-fold by cyclic AMP in vitro with an apparent Km of 83 and 50 nM for fractions FI and FII respectively. Other cyclic 3':5'-nucleotides were effective only at higher concentrations, but even the most effective, cyclic IMP, showed a stimulation nearly an order of magnitude lower than that of cyclic AMP. In contrast, stimulation by cyclic dTMP and cyclic dAMP was very weak. Cyclic AMP showed no significant effect on the apparent Km value of both enzymes for histone and MgCl2 but it somewhat decreased the Km value for ATP. Nucleoside triphosphates like GTP, CTP and UTP inhibited the transfer of [32P]Pi from [gamma-32P]ATP into mixed histone catalysed by membrane-associated kinases either in the presence or in the absence of cyclic AMP. In addition to protein kinases, these membrane fractions also possessed cyclic AMP-binding activities. The apparent association constant (Kalpha) for cyclic AMP binding was 1.0 X 10(10) and 2.6 X 10(10) M for FI and FII membrane fractions respectively.", "contents": "Adenosine 3':5'-cyclic monophosphate-dependent and plasma-membrane-associated protein kinase(s) from bovine corpus luteum. Plasma-membrane fractions FI and FII isolated from bovine corpus luteum by discontinuous sucrose-density-gradient centrifugation, at sucrose-density interfaces of 1.14/1.16 and 1.16/1.18 respectively, contained membrane-associated protein kinases that phosphorylated both the structural proteins of membranes as well as exogenously added protein substrates. Both fractions were characterized with respect to endogenous and exogenous protein substrate specificity, pH-dependence, effect of bivalent metal ions and sensitivity toward cyclic nucleotides. These membrane-associated kinases showed an optimum pH of 6.0 and had an absolute requirement for bivalent metal ions such as Mg2+, Mn2+, or Co2+ that cannot be replaced by Ca2+. Both the activities were stimulated two- to four-fold by cyclic AMP in vitro with an apparent Km of 83 and 50 nM for fractions FI and FII respectively. Other cyclic 3':5'-nucleotides were effective only at higher concentrations, but even the most effective, cyclic IMP, showed a stimulation nearly an order of magnitude lower than that of cyclic AMP. In contrast, stimulation by cyclic dTMP and cyclic dAMP was very weak. Cyclic AMP showed no significant effect on the apparent Km value of both enzymes for histone and MgCl2 but it somewhat decreased the Km value for ATP. Nucleoside triphosphates like GTP, CTP and UTP inhibited the transfer of [32P]Pi from [gamma-32P]ATP into mixed histone catalysed by membrane-associated kinases either in the presence or in the absence of cyclic AMP. In addition to protein kinases, these membrane fractions also possessed cyclic AMP-binding activities. The apparent association constant (Kalpha) for cyclic AMP binding was 1.0 X 10(10) and 2.6 X 10(10) M for FI and FII membrane fractions respectively."} {"id": "PMID:174555", "title": "The investigation of substrate-induced changes in subunit interactions in glyceraldehyde 3-phosphate dehydrogenases by measurement of the kinetics and thermodynamics of subunit exchange.", "content": "An investigation was made of changes in subunit interactions in glyceraldehyde 3-phosphate dehydrogenase on binding NAD+, NADH and other substrates by using the previously developed method of measurement of rates and extent of subunit exchange between the rabbit enzyme (R4), yeast enzyme (Y4) and rabbit-yeast hybrid (R2Y2) [Osborne & Hollaway (1974) Biochem. J. 143, 651-662]. The free energy of activation for the conversion of tetramer into dimer for the rabbit enzyme (R4 leads to 2R2) is increased by at least 12kJ/mol in the presence of NAD+. This increase is interpreted in terms of an NAD+-induced 'tightening' of the tetrameric structure probably involving increased interaction at the subunit interfaces across the QR plane of the molecule [see Buehner et al. (1974) J. Mol. Biol. 82, 563-585]. This tightening of the structure only occurs on binding the third NAD+ molecule to a given enzyme molecule. Conversely, binding of NADH causes a decrease in the free energy of activation for the R4 leads to 2R2 and Y4 leads to 2Y2 conversions by at least 10kJ/mol. This is interpreted as a NADH-induced 'loosening' of the structures arising from decreased interactions across the subunit interfaces involving the QR dissociation plane. In the presence of NADH the increase in the rate of subunit exchange is such that it is not possible to separate the hybrid from the other species if electrophoresis is carried out with NADH in the separation media. In the presence of a mixture of NADH and NAD+ the effect of NAD+ on subunit exchange is dominant. The results are discussed in terms of the known co-operativty between binding sites in glyceraldehyde 3-phosphate dehydrogenases.", "contents": "The investigation of substrate-induced changes in subunit interactions in glyceraldehyde 3-phosphate dehydrogenases by measurement of the kinetics and thermodynamics of subunit exchange. An investigation was made of changes in subunit interactions in glyceraldehyde 3-phosphate dehydrogenase on binding NAD+, NADH and other substrates by using the previously developed method of measurement of rates and extent of subunit exchange between the rabbit enzyme (R4), yeast enzyme (Y4) and rabbit-yeast hybrid (R2Y2) [Osborne & Hollaway (1974) Biochem. J. 143, 651-662]. The free energy of activation for the conversion of tetramer into dimer for the rabbit enzyme (R4 leads to 2R2) is increased by at least 12kJ/mol in the presence of NAD+. This increase is interpreted in terms of an NAD+-induced 'tightening' of the tetrameric structure probably involving increased interaction at the subunit interfaces across the QR plane of the molecule [see Buehner et al. (1974) J. Mol. Biol. 82, 563-585]. This tightening of the structure only occurs on binding the third NAD+ molecule to a given enzyme molecule. Conversely, binding of NADH causes a decrease in the free energy of activation for the R4 leads to 2R2 and Y4 leads to 2Y2 conversions by at least 10kJ/mol. This is interpreted as a NADH-induced 'loosening' of the structures arising from decreased interactions across the subunit interfaces involving the QR dissociation plane. In the presence of NADH the increase in the rate of subunit exchange is such that it is not possible to separate the hybrid from the other species if electrophoresis is carried out with NADH in the separation media. In the presence of a mixture of NADH and NAD+ the effect of NAD+ on subunit exchange is dominant. The results are discussed in terms of the known co-operativty between binding sites in glyceraldehyde 3-phosphate dehydrogenases."} {"id": "PMID:174556", "title": "The reaction of Pseudomonas aeruginosa cytochrome c oxidase with carbon monoxide.", "content": "The binding of CO to ascorbate-reduced Pseudomonas cytochrome oxidase was investigated by static-titration, stopped-flow and flash-photolytic techniques. Static-titration data indicated that the binding process was non-stoicheiometric, with a Hill number of 1.44. Stopped-flow kinetics obtained on the binding of CO to reduced Pseudomonas cytochrome oxidase were biphasic in form; the faster rate exhibited a linear dependence on CO concentration with a second-order rate constant of 2 X 10(4) M-1-s-1, whereas the slower reaction rapidly reached a pseudo-first-order rate limit at approx. 1s-1. The relative proportions of the two phases observed in stopped-flow experiments also showed a dependency on CO concentration, the slower phase increasing as the CO concentration decreased. The kinetics of CO recombination after flash-photolytic dissociation of the reduced Pseudomonas cytochrome oxidase-CO complex were also biphasic in character, both phases showing a linear pseudo-first-order rate dependence on CO concentration. The second-order rate constants were determined as 3.6 X 10(4)M-1-s-1 and 1.6 X 10(4)M-1-s-1 respectively. Again the relative proportions of the two phases varied with CO concentration, the slower phase predominating at low CO concentrations. CO dissociation from the enzyme-CO complex measured in the presence of O2 and NO indicated the presence of two rates, of the order of 0.03s-1 and 0.15s-1. When sodium dithionite was used as a reducing agent for the Pseudomonas cytochrome oxidase, the CO-combination kinetics observed by both stopped flow and flash photolysis were extremely complex and not able to be simply analysed.", "contents": "The reaction of Pseudomonas aeruginosa cytochrome c oxidase with carbon monoxide. The binding of CO to ascorbate-reduced Pseudomonas cytochrome oxidase was investigated by static-titration, stopped-flow and flash-photolytic techniques. Static-titration data indicated that the binding process was non-stoicheiometric, with a Hill number of 1.44. Stopped-flow kinetics obtained on the binding of CO to reduced Pseudomonas cytochrome oxidase were biphasic in form; the faster rate exhibited a linear dependence on CO concentration with a second-order rate constant of 2 X 10(4) M-1-s-1, whereas the slower reaction rapidly reached a pseudo-first-order rate limit at approx. 1s-1. The relative proportions of the two phases observed in stopped-flow experiments also showed a dependency on CO concentration, the slower phase increasing as the CO concentration decreased. The kinetics of CO recombination after flash-photolytic dissociation of the reduced Pseudomonas cytochrome oxidase-CO complex were also biphasic in character, both phases showing a linear pseudo-first-order rate dependence on CO concentration. The second-order rate constants were determined as 3.6 X 10(4)M-1-s-1 and 1.6 X 10(4)M-1-s-1 respectively. Again the relative proportions of the two phases varied with CO concentration, the slower phase predominating at low CO concentrations. CO dissociation from the enzyme-CO complex measured in the presence of O2 and NO indicated the presence of two rates, of the order of 0.03s-1 and 0.15s-1. When sodium dithionite was used as a reducing agent for the Pseudomonas cytochrome oxidase, the CO-combination kinetics observed by both stopped flow and flash photolysis were extremely complex and not able to be simply analysed."} {"id": "PMID:174557", "title": "The reversible delipidation of a solubilized sodium-plus-potassium ion-dependent adenosine triphosphatase from the salt gland of the spiny dogfish.", "content": "A microsomal fraction rich in Na+, K+-ATPase (sodium-plus-potassium ion-dependent adenosine triphosphatase) and the corresponding K+-dependent p-nitrophenyl phosphatase from the rectal salt gland of the spiny dogfish was solubilized by treatment with deoxycholate at high ionic strength. On gel filtration through Sepharose 6B, the ATPase apoenzyme could be separated, in apparently soluble form, from the tissue-fraction phospholipids and was almost free of enzymic activity (2% of the p-nitrophenyl phosphatase activity and 0.2% of the ATPase activity being recovered). On mixing the apoenzyme with an activator consisting of cooked ox brain, a large proportion of the original enzymic activity was obtained. Specific activities of the re-activated enzyme were somewhat higher than in the material before gel filtration: values of 1300-1450 mumol and 250-290 mumol/h per mg of protein were obtained for the hydrolysis of ATP and of p-nitrophenyl phosphate respectively. The activity was inhibitible by ouabain.", "contents": "The reversible delipidation of a solubilized sodium-plus-potassium ion-dependent adenosine triphosphatase from the salt gland of the spiny dogfish. A microsomal fraction rich in Na+, K+-ATPase (sodium-plus-potassium ion-dependent adenosine triphosphatase) and the corresponding K+-dependent p-nitrophenyl phosphatase from the rectal salt gland of the spiny dogfish was solubilized by treatment with deoxycholate at high ionic strength. On gel filtration through Sepharose 6B, the ATPase apoenzyme could be separated, in apparently soluble form, from the tissue-fraction phospholipids and was almost free of enzymic activity (2% of the p-nitrophenyl phosphatase activity and 0.2% of the ATPase activity being recovered). On mixing the apoenzyme with an activator consisting of cooked ox brain, a large proportion of the original enzymic activity was obtained. Specific activities of the re-activated enzyme were somewhat higher than in the material before gel filtration: values of 1300-1450 mumol and 250-290 mumol/h per mg of protein were obtained for the hydrolysis of ATP and of p-nitrophenyl phosphate respectively. The activity was inhibitible by ouabain."} {"id": "PMID:174558", "title": "Physicochemical characterization of the four-iron-four-sulphide ferredoxin from Bacillus stearothermophilus.", "content": "1. A stable ferredoxin was prepared from Bacillus stearothermophilus and purified by chromatography on DEAE-cellulose and by electrophoresis. 2. The minimum molecular weight determined from the amino acid composition was about 7900 and this was in reasonable agreement with a value of 8500 determined by polyacrylamide-gel electrophoresis. The ferredoxin contained four iron atoms and four labile sulphide groups per molecule. 3. The optical absorption, optical-rotatory-dispersion and circular-dichroism spectra are typical of ferredoxins containing 4Fe-4S clusters. 4. Oxidation-reduction titrations, combined with electron-paramagnetic-resonance (e.p.r.) spectroscopy, showed that the protein has a mid-point potential, at pH8, of -280 +/- 10mV, and that only one electron-accepting paramagnetic species is present. 5. The e.p.r. spectrum of the reduced ferredoxin is more readily saturated with microwave power at low temperatures than those of the eight-iron ferredoxins, indicating that there is another mechanism of electron-spin relaxation in the latter. 6. Mossbauer spectra of both redox states were observed over a range of temperatures and in magnetic fields. At high temperatures (77 degrees K and above) both redox states appear as quadrupole-split doublets; in the reduced state two resolved doublets are seen, suggesting appreciable localization of the additional reducing electron. 7. The average chemical shift indicates formal valences of two Fe3+ and two Fe2+ in the oxidized state and three Fe2+ and one Fe3+ in the reduced state. However, the spectra indicate that there are differing degrees of electron delocalization over the iron atoms. 8. At low temperatures (4.2 degrees K) the oxidized form shows no hyperfine magnetic interaction, even in an applied magnetic field, evidence that the oxidized ferredoxin is in a non-magnetic state as a result of antiferromagnetic coupling between the iron atoms. 9. At 4.2 degrees K the reduced form shows a broad asymmetric pattern resulting from magnetic hyperfine interaction. This contrasts with the reduced ferredoxin of Clostridium pasteurianum, which shows a doublet, suggesting that in the latter there may be interaction between the two 4Fe-4S centres. 10. In large applied magnetic fields, positive and negative hyperfine fields are seen in the Mossbauer spectra of the reduced ferredoxin, evidence for antiferromagnetic coupling between the iron atoms in the 4Fe-4S centre. The high-field spectra of the reduced ferredoxin of B. stearothermophilus are similar to those of the reduced ferredoxin of C. pasteurianum.", "contents": "Physicochemical characterization of the four-iron-four-sulphide ferredoxin from Bacillus stearothermophilus. 1. A stable ferredoxin was prepared from Bacillus stearothermophilus and purified by chromatography on DEAE-cellulose and by electrophoresis. 2. The minimum molecular weight determined from the amino acid composition was about 7900 and this was in reasonable agreement with a value of 8500 determined by polyacrylamide-gel electrophoresis. The ferredoxin contained four iron atoms and four labile sulphide groups per molecule. 3. The optical absorption, optical-rotatory-dispersion and circular-dichroism spectra are typical of ferredoxins containing 4Fe-4S clusters. 4. Oxidation-reduction titrations, combined with electron-paramagnetic-resonance (e.p.r.) spectroscopy, showed that the protein has a mid-point potential, at pH8, of -280 +/- 10mV, and that only one electron-accepting paramagnetic species is present. 5. The e.p.r. spectrum of the reduced ferredoxin is more readily saturated with microwave power at low temperatures than those of the eight-iron ferredoxins, indicating that there is another mechanism of electron-spin relaxation in the latter. 6. Mossbauer spectra of both redox states were observed over a range of temperatures and in magnetic fields. At high temperatures (77 degrees K and above) both redox states appear as quadrupole-split doublets; in the reduced state two resolved doublets are seen, suggesting appreciable localization of the additional reducing electron. 7. The average chemical shift indicates formal valences of two Fe3+ and two Fe2+ in the oxidized state and three Fe2+ and one Fe3+ in the reduced state. However, the spectra indicate that there are differing degrees of electron delocalization over the iron atoms. 8. At low temperatures (4.2 degrees K) the oxidized form shows no hyperfine magnetic interaction, even in an applied magnetic field, evidence that the oxidized ferredoxin is in a non-magnetic state as a result of antiferromagnetic coupling between the iron atoms. 9. At 4.2 degrees K the reduced form shows a broad asymmetric pattern resulting from magnetic hyperfine interaction. This contrasts with the reduced ferredoxin of Clostridium pasteurianum, which shows a doublet, suggesting that in the latter there may be interaction between the two 4Fe-4S centres. 10. In large applied magnetic fields, positive and negative hyperfine fields are seen in the Mossbauer spectra of the reduced ferredoxin, evidence for antiferromagnetic coupling between the iron atoms in the 4Fe-4S centre. The high-field spectra of the reduced ferredoxin of B. stearothermophilus are similar to those of the reduced ferredoxin of C. pasteurianum."} {"id": "PMID:174559", "title": "Initiation factors in protein synthesis by free and membrane-bound polyribosomes of liver and hepatoma.", "content": "The activity of initiation factors obtained from free and membrane-bound polyribosomes of liver and of transplantable H5123 hepatoma of rats was investigated by using an assay of protein synthesis in vitro in which poly (U)-directed polyphenylalanine synthesis was measured. Initiation factors of membrane-bound polyribosomes prepared by using the anionic detergent deoxycholate exhibited less activity in incorporating [14C]phenylalanyltRNA into polypetides than did initiation factors of free polyribosomes. However, when membrane-bound polyribosomes were prepared after using the non-ionic detergent Triton X-100, no significant differences in activities in polyphenylalanine synthesis were observed between the initiation factors of free and membrane-bound polyribosomes. These results suggest that Triton X-100 is preferable to deoxycholate in the isolation of of initiation factors from polyribosomes. Initiation factors, prepared by using Triton X-100, of free polyribosomes of hepatoma exhibited greater activity in the stimulation of polyphenylalanine synthesis than did the initiation factors of free or membrane-bound polyribosomes of host livers or of membrane-bound polyribosomes of hepatomas.", "contents": "Initiation factors in protein synthesis by free and membrane-bound polyribosomes of liver and hepatoma. The activity of initiation factors obtained from free and membrane-bound polyribosomes of liver and of transplantable H5123 hepatoma of rats was investigated by using an assay of protein synthesis in vitro in which poly (U)-directed polyphenylalanine synthesis was measured. Initiation factors of membrane-bound polyribosomes prepared by using the anionic detergent deoxycholate exhibited less activity in incorporating [14C]phenylalanyltRNA into polypetides than did initiation factors of free polyribosomes. However, when membrane-bound polyribosomes were prepared after using the non-ionic detergent Triton X-100, no significant differences in activities in polyphenylalanine synthesis were observed between the initiation factors of free and membrane-bound polyribosomes. These results suggest that Triton X-100 is preferable to deoxycholate in the isolation of of initiation factors from polyribosomes. Initiation factors, prepared by using Triton X-100, of free polyribosomes of hepatoma exhibited greater activity in the stimulation of polyphenylalanine synthesis than did the initiation factors of free or membrane-bound polyribosomes of host livers or of membrane-bound polyribosomes of hepatomas."} {"id": "PMID:174704", "title": "Electron spin resonance study of changes during the development of a mouse myeloid leukaemia. II. The ascorbyl radical.", "content": "The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood, spleen and liver of RF/J female mice throughout the development of a myeloid leukaemia. Changes in the concentration of the radical were detectable from an early stage in the disease and did not appear to be directly due to the leukaemic cells but could possibly be due to a reaction against them. Changes in the concentration of the paramagnetic metal ions during the leukaemia have been reported previously and it was found that changes in some of these species correlated with changes in the ascorbyl radical concentration.", "contents": "Electron spin resonance study of changes during the development of a mouse myeloid leukaemia. II. The ascorbyl radical. The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood, spleen and liver of RF/J female mice throughout the development of a myeloid leukaemia. Changes in the concentration of the radical were detectable from an early stage in the disease and did not appear to be directly due to the leukaemic cells but could possibly be due to a reaction against them. Changes in the concentration of the paramagnetic metal ions during the leukaemia have been reported previously and it was found that changes in some of these species correlated with changes in the ascorbyl radical concentration."} {"id": "PMID:174701", "title": "[Severe mixed immunodeficiency. Report of a case].", "content": "The case of a 3 month old child with severe combined sex linked immunodeficiency is presented. The diagnosis was well doccumented, during his life. The child presented as a case of mucocutaneous moniliasis resistant to treatment. There was a history of similar cases in the family; diagnosis was made at post-mortem in one cousin and death occurred at early age in all kins so affected. Blood marrow transplant was not feasible in our case because histocompatibility was lacking in the kins studied. Three units of transfer factor were given as well as hyperimmune plasma but the child died in respiratory failure. Autopsy demonstrated pulmonary infection by Pneumocystic carinii and generalized citomegalic inclussion virus infection; almost complete absence of immune tissue was also demonstrated.", "contents": "[Severe mixed immunodeficiency. Report of a case]. The case of a 3 month old child with severe combined sex linked immunodeficiency is presented. The diagnosis was well doccumented, during his life. The child presented as a case of mucocutaneous moniliasis resistant to treatment. There was a history of similar cases in the family; diagnosis was made at post-mortem in one cousin and death occurred at early age in all kins so affected. Blood marrow transplant was not feasible in our case because histocompatibility was lacking in the kins studied. Three units of transfer factor were given as well as hyperimmune plasma but the child died in respiratory failure. Autopsy demonstrated pulmonary infection by Pneumocystic carinii and generalized citomegalic inclussion virus infection; almost complete absence of immune tissue was also demonstrated."} {"id": "PMID:174705", "title": "Murine leukaemia virus expression in the AKR following thymectomy.", "content": "Thymectomy effectively prevents the development of spontaneous lymphoma in the AKR but how this effect is achieved remains to be determined. One possible mechanism, namely suppression of genomic expression of the oncogenic murine leukaemia virus now seems unlikely since levels of the group specific MuLV antigen were in comparision with their sham operated controls unaltered in both neonatally and adult thymectomized AKR.", "contents": "Murine leukaemia virus expression in the AKR following thymectomy. Thymectomy effectively prevents the development of spontaneous lymphoma in the AKR but how this effect is achieved remains to be determined. One possible mechanism, namely suppression of genomic expression of the oncogenic murine leukaemia virus now seems unlikely since levels of the group specific MuLV antigen were in comparision with their sham operated controls unaltered in both neonatally and adult thymectomized AKR."} {"id": "PMID:174702", "title": "[Intraspinal tumors in children. Review of 24 cases].", "content": "The clinical cases of 24 patients with intraspinal neoplasms seen at the Neurology and Neurosurgery ward of the Hospital del Nino IMAN, in a period of four and a half years are reviewed. The majority of our cases were diagnosed as suffering from tumors of embryological origin like teratomas, dermoid cysts and neuroblastomas. The signs and symptoms were reviewed, noting the importance of weakness of the lower extremities, the alteration in reflexes and sensitivity as well as back pain. We emphasize the great help of the X ray examination of the spinal colum, both plain and with contrast media. The treatment that our patients underwent was reviewed and the results were evaluated, pointing out the fact that life prognosis is related to malignancy of the lesions and the neurological sequelae are intimatly related with the early diagnosis and treatment of this type of lesions.", "contents": "[Intraspinal tumors in children. Review of 24 cases]. The clinical cases of 24 patients with intraspinal neoplasms seen at the Neurology and Neurosurgery ward of the Hospital del Nino IMAN, in a period of four and a half years are reviewed. The majority of our cases were diagnosed as suffering from tumors of embryological origin like teratomas, dermoid cysts and neuroblastomas. The signs and symptoms were reviewed, noting the importance of weakness of the lower extremities, the alteration in reflexes and sensitivity as well as back pain. We emphasize the great help of the X ray examination of the spinal colum, both plain and with contrast media. The treatment that our patients underwent was reviewed and the results were evaluated, pointing out the fact that life prognosis is related to malignancy of the lesions and the neurological sequelae are intimatly related with the early diagnosis and treatment of this type of lesions."} {"id": "PMID:174706", "title": "Serum immunoglobulin levels in primary liver cancer: relationship to underlying cirrhosis and hepatitis-B (surface) antigenaemia.", "content": "Serum IgG, IgM and IgA levels were measured by the single radial diffusion method in 107 South African Negro patients with primary hepatocellular cancer (PHC) and 112 healthy Negro blood donors. The mean serum IgG ANd IgM concentrations were significantly higher (P less than 0-001) in the PHC patients. In those patients in whom PHC was associated with cirrhosis, the serum IgG level was greater (P less than 0-02) than in those without cirrhosis. However, the mean serum IgG concentration in the non-cirrhotic cancer patients was still significantly higher than the control value (P less than 0-001). Thus, while cirrhosis may contribute to the raised IgG levels in PHC, other factors must also be involved. There was no difference in the serum immunoglobulin concentrations in PHC patients with and without hepatitis-B antigenaemia.", "contents": "Serum immunoglobulin levels in primary liver cancer: relationship to underlying cirrhosis and hepatitis-B (surface) antigenaemia. Serum IgG, IgM and IgA levels were measured by the single radial diffusion method in 107 South African Negro patients with primary hepatocellular cancer (PHC) and 112 healthy Negro blood donors. The mean serum IgG ANd IgM concentrations were significantly higher (P less than 0-001) in the PHC patients. In those patients in whom PHC was associated with cirrhosis, the serum IgG level was greater (P less than 0-02) than in those without cirrhosis. However, the mean serum IgG concentration in the non-cirrhotic cancer patients was still significantly higher than the control value (P less than 0-001). Thus, while cirrhosis may contribute to the raised IgG levels in PHC, other factors must also be involved. There was no difference in the serum immunoglobulin concentrations in PHC patients with and without hepatitis-B antigenaemia."} {"id": "PMID:174707", "title": "The leucocyte adherence inhibtion test in cancer of the large bowel.", "content": "A recently introduced assay of cell mediated immunity and humoral inhibitory factors has been evaluated in colorectal cancer patients. Using a perchloric acid extract of adenocarcinoma of the large bowel as antigen, 16/27 patients with colorectal cancer had significant cellular reactivity when their separated peripheral leucocytes were tested in homologous AB serum. In autologous serum only 7/27 had significant reactivity; 6/20 patients with a variety of other malignancies showed sensitization to the colorectal antigen preparation. It is concluded that the leucocyte adherence inhibiton test may offer a simple method of assaying for serum blocking factors in sequential studies but will be of little value in the diagnosis of large bowel cancer.", "contents": "The leucocyte adherence inhibtion test in cancer of the large bowel. A recently introduced assay of cell mediated immunity and humoral inhibitory factors has been evaluated in colorectal cancer patients. Using a perchloric acid extract of adenocarcinoma of the large bowel as antigen, 16/27 patients with colorectal cancer had significant cellular reactivity when their separated peripheral leucocytes were tested in homologous AB serum. In autologous serum only 7/27 had significant reactivity; 6/20 patients with a variety of other malignancies showed sensitization to the colorectal antigen preparation. It is concluded that the leucocyte adherence inhibiton test may offer a simple method of assaying for serum blocking factors in sequential studies but will be of little value in the diagnosis of large bowel cancer."} {"id": "PMID:174708", "title": "The activities of some polycyclic hydrocarbons and their \"K region\" epoxides in an in vitro-in vivo carcinogenicity test system.", "content": "Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, dibenz(a)anthracene and benzo(a)pyrene and their related \"K region\" epoxides were tested for carcinogenic activities using a system in which mouse lung tissue was incubated in the presence of the test compound for 30 min and then implanted into isologous mice. Only 7,12-dimethylbenz(a)anthracene showed any marked carcinogenic activity under the conditions used, but all the compounds tested produced extensive proliferative outgrowths in the implanted tissues that may represent specific responses to the carcinogens.", "contents": "The activities of some polycyclic hydrocarbons and their \"K region\" epoxides in an in vitro-in vivo carcinogenicity test system. Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, dibenz(a)anthracene and benzo(a)pyrene and their related \"K region\" epoxides were tested for carcinogenic activities using a system in which mouse lung tissue was incubated in the presence of the test compound for 30 min and then implanted into isologous mice. Only 7,12-dimethylbenz(a)anthracene showed any marked carcinogenic activity under the conditions used, but all the compounds tested produced extensive proliferative outgrowths in the implanted tissues that may represent specific responses to the carcinogens."} {"id": "PMID:174709", "title": "The role of microsomal hydroxylases in the modification of chloroform hepatotoxicity in rats.", "content": "Male rats have a greater microsomal amidopyrine N-demethylase activity per unit weight of liver, a shorter hexobarbitone sleeping time and are more susceptible to the hepatotoxic effect of chloroform than female rats. Phenobarbitone sodium, phenylbutazone and DDT induce microsomal amidopyrine N-demethylase in the liver of the male rat and reduce hexobarbitone sleeping time. Chlorpromazine is less effective in this respect. Phenobarbitone, phenylbutazone and, to a lesser extent, chlorpromazine potentiate the hepatotoxic effect of chloroform in male rats. SKF 525A, sodium diethyl-dithiocarbamate and carbon disulphide increase hexabarbitone sleeping time in male rats and protect to varying degrees against the hepatotoxic effect of chloroform.", "contents": "The role of microsomal hydroxylases in the modification of chloroform hepatotoxicity in rats. Male rats have a greater microsomal amidopyrine N-demethylase activity per unit weight of liver, a shorter hexobarbitone sleeping time and are more susceptible to the hepatotoxic effect of chloroform than female rats. Phenobarbitone sodium, phenylbutazone and DDT induce microsomal amidopyrine N-demethylase in the liver of the male rat and reduce hexobarbitone sleeping time. Chlorpromazine is less effective in this respect. Phenobarbitone, phenylbutazone and, to a lesser extent, chlorpromazine potentiate the hepatotoxic effect of chloroform in male rats. SKF 525A, sodium diethyl-dithiocarbamate and carbon disulphide increase hexabarbitone sleeping time in male rats and protect to varying degrees against the hepatotoxic effect of chloroform."} {"id": "PMID:174710", "title": "The surface properties of the lung in rats with alveolar lipo-proteinosis.", "content": "The physical behaviour of the intact lungs and of lung extracts from rats affected by alveolar lipo-proteinsosis as a consequence of silica inhalation, was studied by means of pressure volume relations and surface tension area loops. Air inflation of diseased lungs occurred at a lower pressure and collapse was less on deflation than in control specimens, although there appeared to be little change in elastic forces. When saline was used dusted rat lungs showed at higher lung volumes a peculiar hysteresis effect which is attributable to consolidation of alveoli by the lipid material. Extracts from affected lungs showed differences from controls in respect of maximum and minimum surface tensions and stability index but all the values fell within the accepted limits of normal. However, with extracts from pathological lungs the area of the hysteresis loop increased, the shape of the surface tension area curve was abnormal and the percentage compression required to reduce the surface tension to 120 muN/cm fell. Extracts from diseased lungs depressed the maximum surface tension of normal lung extracts and increased the hysteresis area but had little effect on the minimum tension, the stability index or the % compression to achieve 120 muN/cm. The response was thus mainly that of an extract from a dusted rat. The surface activity of phospholipids may be affected by neutral lipid, cholesterol and the products of cell breakdown, all of which occur in the alveolar material. The occurrence within the same lung of compunds which reduce surface tension and others which modify the same lung of compounds which reduce surface tension and others which modify this property suggests that their relative concentrations may determine the overall effectiveness of the lung lining.", "contents": "The surface properties of the lung in rats with alveolar lipo-proteinosis. The physical behaviour of the intact lungs and of lung extracts from rats affected by alveolar lipo-proteinsosis as a consequence of silica inhalation, was studied by means of pressure volume relations and surface tension area loops. Air inflation of diseased lungs occurred at a lower pressure and collapse was less on deflation than in control specimens, although there appeared to be little change in elastic forces. When saline was used dusted rat lungs showed at higher lung volumes a peculiar hysteresis effect which is attributable to consolidation of alveoli by the lipid material. Extracts from affected lungs showed differences from controls in respect of maximum and minimum surface tensions and stability index but all the values fell within the accepted limits of normal. However, with extracts from pathological lungs the area of the hysteresis loop increased, the shape of the surface tension area curve was abnormal and the percentage compression required to reduce the surface tension to 120 muN/cm fell. Extracts from diseased lungs depressed the maximum surface tension of normal lung extracts and increased the hysteresis area but had little effect on the minimum tension, the stability index or the % compression to achieve 120 muN/cm. The response was thus mainly that of an extract from a dusted rat. The surface activity of phospholipids may be affected by neutral lipid, cholesterol and the products of cell breakdown, all of which occur in the alveolar material. The occurrence within the same lung of compunds which reduce surface tension and others which modify the same lung of compounds which reduce surface tension and others which modify this property suggests that their relative concentrations may determine the overall effectiveness of the lung lining."} {"id": "PMID:174711", "title": "The significance of plasma lipoproteins on erythrocyte aggregation and sedimentation.", "content": "Increased erythrocyte aggregation can be induced by high concentrations of human lipoproteins. The dependence of aggregate formation on lipoprotein concentration was recorded by determination of erythrocyte sedimentation rate (ESR), by electrical measurement of the erythrocyte aggregation index (EAI) and by scanning electron microscopy. The lipoprotein concentrations necessary to induce a significantly increased ESR in an otherwise normal human plasma are much too high to be encountered in physiologic or even severe pathologic states. Therefore hyperlipoproteinaemia by itself cannot explain a raised ESR. In cases where the ESR is raised due to the presence of increased amounts of other erythrocyte aggregating plasma proteins (agglomerins), hyperlipoproteinaemia can contribute to a limited extent to the increase in ESR. The possible pathophysiological significance of the demonstrated erythrocyte aggregating capacity of human lipoproteins in a microvascular environment is noted.", "contents": "The significance of plasma lipoproteins on erythrocyte aggregation and sedimentation. Increased erythrocyte aggregation can be induced by high concentrations of human lipoproteins. The dependence of aggregate formation on lipoprotein concentration was recorded by determination of erythrocyte sedimentation rate (ESR), by electrical measurement of the erythrocyte aggregation index (EAI) and by scanning electron microscopy. The lipoprotein concentrations necessary to induce a significantly increased ESR in an otherwise normal human plasma are much too high to be encountered in physiologic or even severe pathologic states. Therefore hyperlipoproteinaemia by itself cannot explain a raised ESR. In cases where the ESR is raised due to the presence of increased amounts of other erythrocyte aggregating plasma proteins (agglomerins), hyperlipoproteinaemia can contribute to a limited extent to the increase in ESR. The possible pathophysiological significance of the demonstrated erythrocyte aggregating capacity of human lipoproteins in a microvascular environment is noted."} {"id": "PMID:174712", "title": "A comparison of membrane glycoconjugates from mouse cells transformed by murine and primate RNA sarcoma viruses.", "content": "Kirsten murine sarcoma virus (Ki-MSV) transformed Balb/eT3 mouse cells (K-Balb) were found to have altered membrane glycoconjugates compared to normal Balb/3T3 cells. There were reduced amounts of mono- and disialogangliosides, GM1 and GD1a, and activity of the specific galactosyltransferase required for synthesis of these gangliosides was reduced to between 0 and 18.5% of normal in the several K-Balb clones examined. When fucose-labeled glycopeptides derived from the surfaces of Balb/3T3 and K-Balb cells were compared by gel filtration chromatography, the glycopeptides from the transformed cells were enriched in earlier eluting components. These differences were also observed when the glycopeptides were derived from the entire cell and were diminished when the surface or cellular glycopeptides from Balb/3T3 and K-Balb were digested with neuraminidase prior to chromatographic analysis. Changes in these membrane sialoglycolipids and sialoglycopeptides were not influenced by Rauscher leukemia virus infection. In marked contrast, these changes in membrane glycoconjugates were not observed in Wooley monkey sarcoma virus (WSV) transformed Balb/3T3 cells (W-Balb). Although W-Balb cells like K-Balb were transformed by tissue culture criteria, their ganglioside composition, galactosyltransferase activity, and glycopeptide patterns were similar to normal Balb/3T3. These findings have potential implications concerning the role of these complex carbohydrates in the phenotypic alterations of transformed cells.", "contents": "A comparison of membrane glycoconjugates from mouse cells transformed by murine and primate RNA sarcoma viruses. Kirsten murine sarcoma virus (Ki-MSV) transformed Balb/eT3 mouse cells (K-Balb) were found to have altered membrane glycoconjugates compared to normal Balb/3T3 cells. There were reduced amounts of mono- and disialogangliosides, GM1 and GD1a, and activity of the specific galactosyltransferase required for synthesis of these gangliosides was reduced to between 0 and 18.5% of normal in the several K-Balb clones examined. When fucose-labeled glycopeptides derived from the surfaces of Balb/3T3 and K-Balb cells were compared by gel filtration chromatography, the glycopeptides from the transformed cells were enriched in earlier eluting components. These differences were also observed when the glycopeptides were derived from the entire cell and were diminished when the surface or cellular glycopeptides from Balb/3T3 and K-Balb were digested with neuraminidase prior to chromatographic analysis. Changes in these membrane sialoglycolipids and sialoglycopeptides were not influenced by Rauscher leukemia virus infection. In marked contrast, these changes in membrane glycoconjugates were not observed in Wooley monkey sarcoma virus (WSV) transformed Balb/3T3 cells (W-Balb). Although W-Balb cells like K-Balb were transformed by tissue culture criteria, their ganglioside composition, galactosyltransferase activity, and glycopeptide patterns were similar to normal Balb/3T3. These findings have potential implications concerning the role of these complex carbohydrates in the phenotypic alterations of transformed cells."} {"id": "PMID:174713", "title": "2' Derivatives of guanosine and inosine cyclic 3',5'-phosphates. Synthesis, enzymic activity, and the effect of 8-substituents.", "content": "A series of representative derivatives of guanosine cyclic 3',5'-phosphate (cGMP) and inosine cyclic 3',5'-phosphate (cIMP) which contained modifications in either the 2' position or the 8 and 2' positions were synthesized. Three types of derivatives were investigated: (1) derivatives in which the 2' position has been altered to produce a 2'-deoxynucleoside cyclic 3',5'-phosphate or a 9-beta-D-arabinofuranosylpurine cyclic 3',5'-phosphate; (2) 2'-omicron-acyl derivatives; and (3) doubly modified derivatives containing a 2' modification [as in (1) and (2)] and an 8-substitution. 2'-Deoxyinosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosylhypoxanthine cyclic 3',5'-phosphate were obtained by HNO2 deamination of 2'-deoxyadenosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosyladenine cyclic 3',5'-phosphate (ara-cAMP), respectively. Treatment of 8-bromo-2'-omicron-(p-toluenesulfonyl) adenosine cyclic 3',5'-phosphate with NaSH yielded the intermediate 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoadenine cyclic 3',5-phosphate, which was converted directly to 2'-deoxyadenosine cyclic 3',5'-phosphate (dcAMP) by treatment with Raney nickel. 8-Bromo-2'-omicron-(p-toluenesulfonyl) guanosine cyclic 3',5'-phosphate was converted to 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate, and the latter was desulfurized with Raney nickel to give 2-deoxyguanosine cyclic 3',5'-phosphate. Ara-cAMP, 9-beta-D-arabinofuranosylguanine cyclic 3',5'-phosphate, and 9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate have been previously reported (Mian et al. (1974), J. Med. Chem. 17, 259). 8-Bromo-2'-omicron-acetylinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]-2'-omicron-acetylinosine cyclic 3',5'-phosphate were produced by acylation of 8-bromoinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]inosine cyclic 3',5'-phosphate, respectively; while 8-bromo-2'-omicron-butyrylguanosine cyclic 3',5'-phosphate was synthesized by bromination of 2'-omicron-butyrylguanosine cyclic 3',5'-phosphate.", "contents": "2' Derivatives of guanosine and inosine cyclic 3',5'-phosphates. Synthesis, enzymic activity, and the effect of 8-substituents. A series of representative derivatives of guanosine cyclic 3',5'-phosphate (cGMP) and inosine cyclic 3',5'-phosphate (cIMP) which contained modifications in either the 2' position or the 8 and 2' positions were synthesized. Three types of derivatives were investigated: (1) derivatives in which the 2' position has been altered to produce a 2'-deoxynucleoside cyclic 3',5'-phosphate or a 9-beta-D-arabinofuranosylpurine cyclic 3',5'-phosphate; (2) 2'-omicron-acyl derivatives; and (3) doubly modified derivatives containing a 2' modification [as in (1) and (2)] and an 8-substitution. 2'-Deoxyinosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosylhypoxanthine cyclic 3',5'-phosphate were obtained by HNO2 deamination of 2'-deoxyadenosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosyladenine cyclic 3',5'-phosphate (ara-cAMP), respectively. Treatment of 8-bromo-2'-omicron-(p-toluenesulfonyl) adenosine cyclic 3',5'-phosphate with NaSH yielded the intermediate 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoadenine cyclic 3',5-phosphate, which was converted directly to 2'-deoxyadenosine cyclic 3',5'-phosphate (dcAMP) by treatment with Raney nickel. 8-Bromo-2'-omicron-(p-toluenesulfonyl) guanosine cyclic 3',5'-phosphate was converted to 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate, and the latter was desulfurized with Raney nickel to give 2-deoxyguanosine cyclic 3',5'-phosphate. Ara-cAMP, 9-beta-D-arabinofuranosylguanine cyclic 3',5'-phosphate, and 9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate have been previously reported (Mian et al. (1974), J. Med. Chem. 17, 259). 8-Bromo-2'-omicron-acetylinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]-2'-omicron-acetylinosine cyclic 3',5'-phosphate were produced by acylation of 8-bromoinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]inosine cyclic 3',5'-phosphate, respectively; while 8-bromo-2'-omicron-butyrylguanosine cyclic 3',5'-phosphate was synthesized by bromination of 2'-omicron-butyrylguanosine cyclic 3',5'-phosphate."} {"id": "PMID:174714", "title": "Magnetic resonance studies of the proximity and spatial arrangement of propionyl coenzyme A and pyruvate on a biotin-metalloenzyme, transcarboxylase.", "content": "A spin-labeled ester of CoA, R-CoA (3-carboxy-2,2,5,5-tetramethyl-1-pyrolidinyl-1-oxy CoA thioester), has been shown by competition studies using electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) to bind specifically to the propionyl-CoA binding sites of transcarboxylase. Titrations indicate 0.7 +/- 0.2 binding site for R-CoA per enzyme-bound biotin with a dissociation constant of 0.33 +/- 0.12 mM. Propionyl-CoA binds to this site with a 1.3-fold lower disonable agreement with kinetically determined inhibitor constants of CoA and propionyl-CoA and propionyl-CoA (D. B. Northrop (1969), J. Biol. Chem. 244, 5808). The bit of this spin-label on 1/T1 of water protons. The formation of a ternary transcarboxylase-R-CoA-pyruvate complex is suggested by the failure of pyruvate to displace R-CoA from the tight site and is established by the paramagnetic effects of enzyme-bound R-CoA on the relaxation rates of the protons and 13C atoms of enzyme-bound pyruvate. From the paramagnetic effects of R-CoA on the relaxation rates of the methyl protons of pyruvate at 40.5 and 100 MHz, and on the 13C-enriched carbonyl and carboxyl carbon atoms of pyruvate at 25.1 MHz, a correlation time of 7 nsec and distances from the bound nitroxide radical to the methyl protons, the carbonyl, and carboxyl carbon atoms of bound pyruvate of 7.9 +/- 0.7, 10.3 +/- 0.8, and 12.1 +/- 0.9 A, respectively, are calculated. These distances establish the close proximity of the CoA ester and keto acid sites on transcarboxylase. Together with the previously determined distances from the enzyme-bound (Co(II) to the methyl protons and 2 carbon atoms of bound pyruvate and to 12 protons and 3 phosphorus atoms of bound propionyl-CoA, the present distances are used to derive a composite model of the bound substrates in the overall transcarboxylation reaction. In this model the distance from the methyl carbon of pyruvate and the methylene carbon of propionyl-CoA, between which the carboxyl transfer takes place is only approximately 7 A. Depending on the detailed mechanism of the carboxyl transfer, the distance through which the carboxybiotin must migrate is therefore between 0 and 7 A. Hence the major role of the 14-A arm of carboxybiotin is not to permit a large carboxyl migration but, rather to permit carboxybiotin to traverse the gap which occurs at the interface of three subunits and to insinuate itself between the CoA and keto acid sites.", "contents": "Magnetic resonance studies of the proximity and spatial arrangement of propionyl coenzyme A and pyruvate on a biotin-metalloenzyme, transcarboxylase. A spin-labeled ester of CoA, R-CoA (3-carboxy-2,2,5,5-tetramethyl-1-pyrolidinyl-1-oxy CoA thioester), has been shown by competition studies using electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) to bind specifically to the propionyl-CoA binding sites of transcarboxylase. Titrations indicate 0.7 +/- 0.2 binding site for R-CoA per enzyme-bound biotin with a dissociation constant of 0.33 +/- 0.12 mM. Propionyl-CoA binds to this site with a 1.3-fold lower disonable agreement with kinetically determined inhibitor constants of CoA and propionyl-CoA and propionyl-CoA (D. B. Northrop (1969), J. Biol. Chem. 244, 5808). The bit of this spin-label on 1/T1 of water protons. The formation of a ternary transcarboxylase-R-CoA-pyruvate complex is suggested by the failure of pyruvate to displace R-CoA from the tight site and is established by the paramagnetic effects of enzyme-bound R-CoA on the relaxation rates of the protons and 13C atoms of enzyme-bound pyruvate. From the paramagnetic effects of R-CoA on the relaxation rates of the methyl protons of pyruvate at 40.5 and 100 MHz, and on the 13C-enriched carbonyl and carboxyl carbon atoms of pyruvate at 25.1 MHz, a correlation time of 7 nsec and distances from the bound nitroxide radical to the methyl protons, the carbonyl, and carboxyl carbon atoms of bound pyruvate of 7.9 +/- 0.7, 10.3 +/- 0.8, and 12.1 +/- 0.9 A, respectively, are calculated. These distances establish the close proximity of the CoA ester and keto acid sites on transcarboxylase. Together with the previously determined distances from the enzyme-bound (Co(II) to the methyl protons and 2 carbon atoms of bound pyruvate and to 12 protons and 3 phosphorus atoms of bound propionyl-CoA, the present distances are used to derive a composite model of the bound substrates in the overall transcarboxylation reaction. In this model the distance from the methyl carbon of pyruvate and the methylene carbon of propionyl-CoA, between which the carboxyl transfer takes place is only approximately 7 A. Depending on the detailed mechanism of the carboxyl transfer, the distance through which the carboxybiotin must migrate is therefore between 0 and 7 A. Hence the major role of the 14-A arm of carboxybiotin is not to permit a large carboxyl migration but, rather to permit carboxybiotin to traverse the gap which occurs at the interface of three subunits and to insinuate itself between the CoA and keto acid sites."} {"id": "PMID:174715", "title": "5'-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA.", "content": "The 5'-terminal oligonucleotides m7G(5')ppp(5')NmpNp and m7G(5')ppp(5')NmpNmpNp were isolated by DEAE-cellulose column chromatography after enzymatic digestion of 32P- or methyl-3H-labeled poly(A)\" HeLa cell mRNA. The recovery of such oligonucleotides indicated that a high percentage of mRNA has blocked termini. The dimethylated nucleoside, N6, O2'-dimethyladenosine (m6Am), as well as the four common 2'-O-methylribonucleosides (Gm, Am, Um, Cm) were present in the second position linked through the triphosphate bridge to 7-methylguanosine (m7G) whereas little m6Am was in the third position. The only internal methylated nucleoside, N6-methyladenosine (m6A), was found exclusively as m6ApC and Apm6ApC after digestion with RNase A, T1, and alkaline phosphatase. Digestion with RNase A and alkaline phat pyrimidines are present in much smaller amounts or absent from this position. These results imply a considerable sequence specificity since there are thousands of different mRNA species in HeLa cells. Our studies are consistent with the following model of HeLa cell mRNA in which Nm may be m6Am, Gm, Cm, Um, or Am and one or more m6A residues are present at an unspecified internal location: m7G(5')ppp(5')Nm-(Nm)---(G or A)-m6A-C---(A)100-200A.", "contents": "5'-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA. The 5'-terminal oligonucleotides m7G(5')ppp(5')NmpNp and m7G(5')ppp(5')NmpNmpNp were isolated by DEAE-cellulose column chromatography after enzymatic digestion of 32P- or methyl-3H-labeled poly(A)\" HeLa cell mRNA. The recovery of such oligonucleotides indicated that a high percentage of mRNA has blocked termini. The dimethylated nucleoside, N6, O2'-dimethyladenosine (m6Am), as well as the four common 2'-O-methylribonucleosides (Gm, Am, Um, Cm) were present in the second position linked through the triphosphate bridge to 7-methylguanosine (m7G) whereas little m6Am was in the third position. The only internal methylated nucleoside, N6-methyladenosine (m6A), was found exclusively as m6ApC and Apm6ApC after digestion with RNase A, T1, and alkaline phosphatase. Digestion with RNase A and alkaline phat pyrimidines are present in much smaller amounts or absent from this position. These results imply a considerable sequence specificity since there are thousands of different mRNA species in HeLa cells. Our studies are consistent with the following model of HeLa cell mRNA in which Nm may be m6Am, Gm, Cm, Um, or Am and one or more m6A residues are present at an unspecified internal location: m7G(5')ppp(5')Nm-(Nm)---(G or A)-m6A-C---(A)100-200A."} {"id": "PMID:174716", "title": "Nucleotide clusters in deoxyribonucleic acids. Comparison of the sequences of the large pyrimidine oligonucleotides of bacteriophages S13 and phiX174 deoxyribonucleic acids.", "content": "The large pyrimidine oligonucleotides from the DNAs of the two related bacteriophages phiX174 and S13 have been sequenced. The largest pyrimidine oligonucleotide present is unique to S13 DNA and is the undecanucleotide C5T6, sequence C-T-T-C-C-T-C-T-T-C-T. Considerable sequence homology has been found between the pyrimidine oligonucleotides of the two phage DNAs. Out of 14 oligonucleotide sequences from S13 DNA (120 bases) at least ten are identical with sequences of oligonucleotides from phiX174 DNA (92 bases) and two are closely related (17 bases), the only difference being a single thymine to cytosine transition in each sequence (a total of 107 identical bases). The pyrimidine oligonucleotides of each phage DNA show extensive internal sequence homology among each other with up to eight bases identical in sequence in pairs of different oligonucleotides. Another interesting observation is the occurrence of symmetrical sequences (true palindromes) which read the same forwards as backwards. The longest symmetrical sequence is the nonanucleotide C4T5 sequence, C-T-C-T-T-T-C-T-C, present in both S13 and phiX174 DNAs. The extensive sequence homology observed between the pyrimidine oligonucleotides of S13 and phiX174 supports the close relationship of the two phages and provides further evidence that they were derived from recent common ancestors.", "contents": "Nucleotide clusters in deoxyribonucleic acids. Comparison of the sequences of the large pyrimidine oligonucleotides of bacteriophages S13 and phiX174 deoxyribonucleic acids. The large pyrimidine oligonucleotides from the DNAs of the two related bacteriophages phiX174 and S13 have been sequenced. The largest pyrimidine oligonucleotide present is unique to S13 DNA and is the undecanucleotide C5T6, sequence C-T-T-C-C-T-C-T-T-C-T. Considerable sequence homology has been found between the pyrimidine oligonucleotides of the two phage DNAs. Out of 14 oligonucleotide sequences from S13 DNA (120 bases) at least ten are identical with sequences of oligonucleotides from phiX174 DNA (92 bases) and two are closely related (17 bases), the only difference being a single thymine to cytosine transition in each sequence (a total of 107 identical bases). The pyrimidine oligonucleotides of each phage DNA show extensive internal sequence homology among each other with up to eight bases identical in sequence in pairs of different oligonucleotides. Another interesting observation is the occurrence of symmetrical sequences (true palindromes) which read the same forwards as backwards. The longest symmetrical sequence is the nonanucleotide C4T5 sequence, C-T-C-T-T-T-C-T-C, present in both S13 and phiX174 DNAs. The extensive sequence homology observed between the pyrimidine oligonucleotides of S13 and phiX174 supports the close relationship of the two phages and provides further evidence that they were derived from recent common ancestors."} {"id": "PMID:174717", "title": "Synchronous digestion of SV40 DNA by exonuclease III.", "content": "We have established an optimal condition for the synchronous digestion of SV40 DNA with Escherichia coli exonuclease III. Electron microscopy and polyacrylamide gel electrophoresis were used to obtain accurate measurements on the lengths of DNA before and after exonuclease III digestion. Based on this finding, a new method for determining the sequence of long duplex DNA can be realized. It involves (a) the synchronous digestion of the DNA from the 3' ends with exonuclease III, followed by (b) repair synthesis with labeled nucleotides and DNA polymerase, and (c) sequence analysis of the repaired DNA.", "contents": "Synchronous digestion of SV40 DNA by exonuclease III. We have established an optimal condition for the synchronous digestion of SV40 DNA with Escherichia coli exonuclease III. Electron microscopy and polyacrylamide gel electrophoresis were used to obtain accurate measurements on the lengths of DNA before and after exonuclease III digestion. Based on this finding, a new method for determining the sequence of long duplex DNA can be realized. It involves (a) the synchronous digestion of the DNA from the 3' ends with exonuclease III, followed by (b) repair synthesis with labeled nucleotides and DNA polymerase, and (c) sequence analysis of the repaired DNA."} {"id": "PMID:174718", "title": "Conformational equilibria accompanying the electron transfer between cytochrome c (P551) and azurin from Pseudomonas aeruginosa.", "content": "The redox reaction between cytochrome c (Cyt c) (P-551) and the blue copper protein azurin, both from Pseudomonas aeruginosa, was studied using the temperature-jump technique. Two relaxation times were observed in a mechanism assumed to involve three equilibria. The fast relaxation time (0.4 less than tau less than 8 ms) was ascribed to the electron exchange step. The slow relaxation time (tau congruent to 37 ms) was assigned to a conformational equilibrium of the reduced azurin that was coupled through the electron exchange step to a faster conformational equilibrium of the oxidized Cyt c (P551). But because the Cyt c (P551) isomerization, being very rapid, was uncoupled from the two slower equilibria, and was assumed to involve no spectral change, the amplitude of its relaxation time (tau congruent to 0.1 ms) would be zero. At 25 degrees C and pH 7.0 the rate constants for the oxidation and reduction of Cyt c (P551) by azurin were 6.1 X 10(6) and 7.8 X 10(6) M-1 s-1, respectively; for the formation and disappearance of the reactive conformational isomer of azurin they were 12 and 17 s-1, respectively. The rates for the Cyt c (P551) isomerization could only be estimated at approximately 10(4) s-1. The thermodynamic parameters of each reaction step were evaluated from the amplitudes of the relaxations and from Eyring plots of the rate constants. Measurements of the overall equilibrium constant showed it to be temperature independent (5-35 degrees C), i.e. deltaHtot = 0. This zero enthalpy change was found to be compatible with the enthalpies calculated for the individual steps. In the electron exchange equilibrium, the values of the activation enthalpies were two to three times higher than the values published for various low molecular weight reagents in their electron exchange with copper proteins, yet the rate of exchange between Cyt c (P551) and azurin was some hundreds of times faster. This was explained in terms of the measured positive or zero entropies of activation that could result from a high level of specificity between the proteins particularly in areas of complementary charges. The mechanism of electron transfer was considered as essentially an outer sphere reaction, of which the rate could be approximated by the Marcus theory.", "contents": "Conformational equilibria accompanying the electron transfer between cytochrome c (P551) and azurin from Pseudomonas aeruginosa. The redox reaction between cytochrome c (Cyt c) (P-551) and the blue copper protein azurin, both from Pseudomonas aeruginosa, was studied using the temperature-jump technique. Two relaxation times were observed in a mechanism assumed to involve three equilibria. The fast relaxation time (0.4 less than tau less than 8 ms) was ascribed to the electron exchange step. The slow relaxation time (tau congruent to 37 ms) was assigned to a conformational equilibrium of the reduced azurin that was coupled through the electron exchange step to a faster conformational equilibrium of the oxidized Cyt c (P551). But because the Cyt c (P551) isomerization, being very rapid, was uncoupled from the two slower equilibria, and was assumed to involve no spectral change, the amplitude of its relaxation time (tau congruent to 0.1 ms) would be zero. At 25 degrees C and pH 7.0 the rate constants for the oxidation and reduction of Cyt c (P551) by azurin were 6.1 X 10(6) and 7.8 X 10(6) M-1 s-1, respectively; for the formation and disappearance of the reactive conformational isomer of azurin they were 12 and 17 s-1, respectively. The rates for the Cyt c (P551) isomerization could only be estimated at approximately 10(4) s-1. The thermodynamic parameters of each reaction step were evaluated from the amplitudes of the relaxations and from Eyring plots of the rate constants. Measurements of the overall equilibrium constant showed it to be temperature independent (5-35 degrees C), i.e. deltaHtot = 0. This zero enthalpy change was found to be compatible with the enthalpies calculated for the individual steps. In the electron exchange equilibrium, the values of the activation enthalpies were two to three times higher than the values published for various low molecular weight reagents in their electron exchange with copper proteins, yet the rate of exchange between Cyt c (P551) and azurin was some hundreds of times faster. This was explained in terms of the measured positive or zero entropies of activation that could result from a high level of specificity between the proteins particularly in areas of complementary charges. The mechanism of electron transfer was considered as essentially an outer sphere reaction, of which the rate could be approximated by the Marcus theory."} {"id": "PMID:174719", "title": "Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens.", "content": "Collagenase cleavage of human Type II and III collagens has been studied using a highly purified preparation of rabbit tumor collagenase. Progress of the reactions in solution was followed by viscometry and the results indicated that under the conditions employed Type III collagen molecules were cleaved at approximately five times the rate of Type II molecules. Cleavage products of the reactions were isolated in denatured form by agarose molecular sieve chromatography. The molecular weights and amino acid compositions of the products demonstrated that Type II and III molecules had been cleaved at the characteristic three-quarter, one-quarter locus, giving rise to a large fragment derived from the NH2-terminal portion of the molecule and a smaller fragment representing the COOH-terminal region. The amino acid sequence at the NH2-terminal portion of the smaller fragment derived from Type II collagen was determined to be Ile-Ala-Gly-Gln-Arg, and the corresponding region from Type III collagen was found to have the sequence Leu-Ala Gly-Leu-Arg. These sequences for alpha1(II) and alpha1(III) chains adjacent to the site of collagenase cleavage along with previous data for alpha1(I) and alpha2 chains indicate that the minimum specific sequence required for collagenase cleavage is Gly-Ile-Ala or Gly-Leu-Ala. Inspection of the available sequence data for collagen alpha chains indicates that the latter sequences are found in at least three additional locations at which collagenase cleavage does not occur. Each of the sequences which are apparently not substrates for collagenase, however, are followed by a Gly-X-Hyp sequence. We suggest, then, that a minimum of five residues in collagen alpha chains COOH-terminal to the cleavage site comprise the substrate recognition site.", "contents": "Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Collagenase cleavage of human Type II and III collagens has been studied using a highly purified preparation of rabbit tumor collagenase. Progress of the reactions in solution was followed by viscometry and the results indicated that under the conditions employed Type III collagen molecules were cleaved at approximately five times the rate of Type II molecules. Cleavage products of the reactions were isolated in denatured form by agarose molecular sieve chromatography. The molecular weights and amino acid compositions of the products demonstrated that Type II and III molecules had been cleaved at the characteristic three-quarter, one-quarter locus, giving rise to a large fragment derived from the NH2-terminal portion of the molecule and a smaller fragment representing the COOH-terminal region. The amino acid sequence at the NH2-terminal portion of the smaller fragment derived from Type II collagen was determined to be Ile-Ala-Gly-Gln-Arg, and the corresponding region from Type III collagen was found to have the sequence Leu-Ala Gly-Leu-Arg. These sequences for alpha1(II) and alpha1(III) chains adjacent to the site of collagenase cleavage along with previous data for alpha1(I) and alpha2 chains indicate that the minimum specific sequence required for collagenase cleavage is Gly-Ile-Ala or Gly-Leu-Ala. Inspection of the available sequence data for collagen alpha chains indicates that the latter sequences are found in at least three additional locations at which collagenase cleavage does not occur. Each of the sequences which are apparently not substrates for collagenase, however, are followed by a Gly-X-Hyp sequence. We suggest, then, that a minimum of five residues in collagen alpha chains COOH-terminal to the cleavage site comprise the substrate recognition site."} {"id": "PMID:174720", "title": "Translation of collagen messenger RNA in a cell-free system derived from wheat germ.", "content": "A cell-free system for synthesizing protein from wheat germ was used to translate the messenger RNA extracted from 16-day embryonic chick calvaria. A part of the product had properties similar to collagenous peptides and served as a substrate for prolyl hydroxylase, an enzyme specific for collagen. The level of potassium was critical for the synthesis of high molecular weight products with properties similar to pro-alpha-chains. The potassium concentration for optimal protein synthesis, as judged by maximum incorporation of [3H]proline into acid precipitable material, was considerably lower than the concentration required for the synthesis of high molecular weight collagenous peptides.", "contents": "Translation of collagen messenger RNA in a cell-free system derived from wheat germ. A cell-free system for synthesizing protein from wheat germ was used to translate the messenger RNA extracted from 16-day embryonic chick calvaria. A part of the product had properties similar to collagenous peptides and served as a substrate for prolyl hydroxylase, an enzyme specific for collagen. The level of potassium was critical for the synthesis of high molecular weight products with properties similar to pro-alpha-chains. The potassium concentration for optimal protein synthesis, as judged by maximum incorporation of [3H]proline into acid precipitable material, was considerably lower than the concentration required for the synthesis of high molecular weight collagenous peptides."} {"id": "PMID:174721", "title": "Subunit dissociation of mitochondrial malate dehydrogenase.", "content": "Fluorescence polarization studies of porcine mitochondrial malate dehydrogenase labeled with fluorescein isothiocyanate or fluorescamine indicated a concentration-dependent dissociation of the dimeric molecule with a KD OF 2 X 10(7) N at pH 8.0. These results were confirmed by the concentration dependence of the stability of the enzyme at elevated temperatures and the creation of hybrid molecules with fluorescein and Rhodamine B labeled subunits, in which energy transfer was observed. The binding of NADH resulted in a small shift of the subunit dissociation curve toward monomer, demonstrating that monomer has twice the affinity for reduced coenzyme. NAD+ binding prevented dissociation of the dimer, even at concentrations below 10(-8) N. These results indicate that binding of reduced or oxidized coenzymes results in different conformation changes, which are transferred to the subunit interface.", "contents": "Subunit dissociation of mitochondrial malate dehydrogenase. Fluorescence polarization studies of porcine mitochondrial malate dehydrogenase labeled with fluorescein isothiocyanate or fluorescamine indicated a concentration-dependent dissociation of the dimeric molecule with a KD OF 2 X 10(7) N at pH 8.0. These results were confirmed by the concentration dependence of the stability of the enzyme at elevated temperatures and the creation of hybrid molecules with fluorescein and Rhodamine B labeled subunits, in which energy transfer was observed. The binding of NADH resulted in a small shift of the subunit dissociation curve toward monomer, demonstrating that monomer has twice the affinity for reduced coenzyme. NAD+ binding prevented dissociation of the dimer, even at concentrations below 10(-8) N. These results indicate that binding of reduced or oxidized coenzymes results in different conformation changes, which are transferred to the subunit interface."} {"id": "PMID:174722", "title": "Estrogen receptors in the rat uterus. Retention of hormone-receptor complexes.", "content": "The retention pattern and biochemical characteristics of estrogen receptors in the nuclei of uterine cells were studied as a function of time after the in vivo injection of estradiol (E2) to immature female rats. One hour after the injection of 0.1 mug of tritiated E2, approximately 0.20 pmol per uterus of receptor bound hormone is retained in uterine nuclei. This dose of E2 produces a maximal uterotrophic response. Six hours after E2 administration, uterine nuclei retain 0.04-0.08 pmol of hormone per uterus. Hormone receptor complexes extracted from uterine nuclei 1, 3, and 6 h after in vivo injection of hormone have similar structural and binding characteristics. Receptors extracted at all three times sediment at 5S in high salt gradients and have a dissociation binding constant of approximately 3 nM for E2. The wash-out curves of receptors as a function of salt concentration are identical for uterine nuclei from animals treated for 1 or 6 h with estradiol, suggesting that the nature of the nuclear binding of receptors is not altered during this time interval. Experiments utilizing the injection of unlabeled estradiol, followed by an in vitro exchange procedure with tritiated estradiol, indicated that the total nuclear estrogen receptor sites, i.e., filled and vacant, decreased similarly.", "contents": "Estrogen receptors in the rat uterus. Retention of hormone-receptor complexes. The retention pattern and biochemical characteristics of estrogen receptors in the nuclei of uterine cells were studied as a function of time after the in vivo injection of estradiol (E2) to immature female rats. One hour after the injection of 0.1 mug of tritiated E2, approximately 0.20 pmol per uterus of receptor bound hormone is retained in uterine nuclei. This dose of E2 produces a maximal uterotrophic response. Six hours after E2 administration, uterine nuclei retain 0.04-0.08 pmol of hormone per uterus. Hormone receptor complexes extracted from uterine nuclei 1, 3, and 6 h after in vivo injection of hormone have similar structural and binding characteristics. Receptors extracted at all three times sediment at 5S in high salt gradients and have a dissociation binding constant of approximately 3 nM for E2. The wash-out curves of receptors as a function of salt concentration are identical for uterine nuclei from animals treated for 1 or 6 h with estradiol, suggesting that the nature of the nuclear binding of receptors is not altered during this time interval. Experiments utilizing the injection of unlabeled estradiol, followed by an in vitro exchange procedure with tritiated estradiol, indicated that the total nuclear estrogen receptor sites, i.e., filled and vacant, decreased similarly."} {"id": "PMID:174723", "title": "Chemical modification of the tryptophan residue in adrenocorticotropin.", "content": "The single tryptophan residue in the pituitary hormone adrenocorticotropin was modified selectively by reaction with a variety of substituted o-nitrophenylsulfenyl chlorides. In addition to quantitative modification of the tryptophan residue, the reaction invariably resulted in partial oxidation of the methionine residue to the sulfoxide. The methionine sulfoxide derivative could be separated from the desired product by partition chromatography on Sephadex G-50 in the solvent system 1-butanol-pyridine-0.1% acetic acid (5:3:11). Thus, the 2,4-dinitrophenylsulfenyl, 2-nitro-4-carboxyphenylsulfenyl, and 2-nitro-4-carbamidophenylsulfenyl derivatives of adrenocorticotropin were prepared and characterized. Modifications in the isolation of adrenocorticotropin from ovine pituitaries are also described. The melanocyte stimulating activities of the native hormone and the analogues are discussed.", "contents": "Chemical modification of the tryptophan residue in adrenocorticotropin. The single tryptophan residue in the pituitary hormone adrenocorticotropin was modified selectively by reaction with a variety of substituted o-nitrophenylsulfenyl chlorides. In addition to quantitative modification of the tryptophan residue, the reaction invariably resulted in partial oxidation of the methionine residue to the sulfoxide. The methionine sulfoxide derivative could be separated from the desired product by partition chromatography on Sephadex G-50 in the solvent system 1-butanol-pyridine-0.1% acetic acid (5:3:11). Thus, the 2,4-dinitrophenylsulfenyl, 2-nitro-4-carboxyphenylsulfenyl, and 2-nitro-4-carbamidophenylsulfenyl derivatives of adrenocorticotropin were prepared and characterized. Modifications in the isolation of adrenocorticotropin from ovine pituitaries are also described. The melanocyte stimulating activities of the native hormone and the analogues are discussed."} {"id": "PMID:174724", "title": "Preparation of radioiodinated simian virus 40 DNA for use in DNA - DNA reassociation kinetics experiments.", "content": "A method is described for the preparation of 125I-labelled SV40 DNA. Using this method, SV40 DNA can be routinely labelled to 15 - 10(6) dpm per mug; much higher specific activities are easily obtained by minor modifications of the method. Once incorporated, the radioactive label dissociates from DNA exceedingly slowly at 4 degrees C or at 68 degrees C. Iodinated SV40 DNA is shown to be useful in the quantitation of viral nucleic acid sequences in SV40-transformed 3T3 cells by DNA - DNA reassociation kinetics.", "contents": "Preparation of radioiodinated simian virus 40 DNA for use in DNA - DNA reassociation kinetics experiments. A method is described for the preparation of 125I-labelled SV40 DNA. Using this method, SV40 DNA can be routinely labelled to 15 - 10(6) dpm per mug; much higher specific activities are easily obtained by minor modifications of the method. Once incorporated, the radioactive label dissociates from DNA exceedingly slowly at 4 degrees C or at 68 degrees C. Iodinated SV40 DNA is shown to be useful in the quantitation of viral nucleic acid sequences in SV40-transformed 3T3 cells by DNA - DNA reassociation kinetics."} {"id": "PMID:174725", "title": "Partial purification and properties of a DNA-binding protein from nuclei of cells infected with polyoma virus.", "content": "A DNA-binding protein has been purified from nuclei of 3T3 cells infected with polyoma virus. The assay used to detect this activity measures the amount of double-stranded DNA retained on a nitrocellulose membrane filter in the presence of binding protein. The interaction between DNA and protein is salt dependent and occurs optimally at 0.8 M NaCl. The isolated protein can bind to both circular and linear duplex DNA. Incubation of the binding protein with PM2 or polyoma DNA results in the formation of a fast sedimenting DNA structure in neutral sucrose gradients. The isolated binding protein is also capable of producing a considerable stimulation of both Escherichia coli (Pol I) and T4 DNA polymerase activities when either single-stranded or intact, native T7 DNA is used as the template. The binding protein itself is free of detectable DNA polymerase or nuclease activity.", "contents": "Partial purification and properties of a DNA-binding protein from nuclei of cells infected with polyoma virus. A DNA-binding protein has been purified from nuclei of 3T3 cells infected with polyoma virus. The assay used to detect this activity measures the amount of double-stranded DNA retained on a nitrocellulose membrane filter in the presence of binding protein. The interaction between DNA and protein is salt dependent and occurs optimally at 0.8 M NaCl. The isolated protein can bind to both circular and linear duplex DNA. Incubation of the binding protein with PM2 or polyoma DNA results in the formation of a fast sedimenting DNA structure in neutral sucrose gradients. The isolated binding protein is also capable of producing a considerable stimulation of both Escherichia coli (Pol I) and T4 DNA polymerase activities when either single-stranded or intact, native T7 DNA is used as the template. The binding protein itself is free of detectable DNA polymerase or nuclease activity."} {"id": "PMID:174726", "title": "Early androgen action in kidney of normal and androgen-insensitive (tfm/y) mice. Changes in RNA polymerase and chromatin template activities.", "content": "Intranuclear accumulation of testosterone was compared with early changes in transcriptional events in kidneys from normal female and androgen-insensitive (tfm/y) mice. Following a subcutaneous injection of [3H] testosterone, total nuclear uptake of the steroid was maximal at 30 min and declined to about 40% of the peak value by 4 h after hormone administration. After a single subcutaneous dose of testosterone, RNA polymerase activity assayed in intact nuclei in the presence of Mg2+ and alpha-amanitin (nucleolar RNA polymerase I), as well as the enzyme activity sensitive to low concentration of the toxin (nucleoplasmic RNA polymerase II), increased within 15 min and attained peak values at 2 and 1 h, respectively. The activity of both polymerases declined almost to the control level by 4 h and then increased again with a second peak at 20 and 12 h for RNA polymerase I and II, respectively. Similarly, the template capacity of mouse kidney chromatin, as measured with mammalian RNA polymerase II, increased by 15 min, reached a peak at 1 h and returned to control level by 4 h following hormone treatment. A second dose of testosterone given at the nadir (4 h) was not capable of stimulating renal chromatin template activity significantly as compared to the effect observed after the initial hormone treatment. Contrary to the testosterone-stimulated changes in transcriptional events observed in normal female mice, androgens elicited no response in androgen-insensitive tfm/y mice, animals lacking cytosol androgen receptors. These results strongly support the contention that hormone-specific receptors are obligatory to steroid-mediated modifications in gene transcription.", "contents": "Early androgen action in kidney of normal and androgen-insensitive (tfm/y) mice. Changes in RNA polymerase and chromatin template activities. Intranuclear accumulation of testosterone was compared with early changes in transcriptional events in kidneys from normal female and androgen-insensitive (tfm/y) mice. Following a subcutaneous injection of [3H] testosterone, total nuclear uptake of the steroid was maximal at 30 min and declined to about 40% of the peak value by 4 h after hormone administration. After a single subcutaneous dose of testosterone, RNA polymerase activity assayed in intact nuclei in the presence of Mg2+ and alpha-amanitin (nucleolar RNA polymerase I), as well as the enzyme activity sensitive to low concentration of the toxin (nucleoplasmic RNA polymerase II), increased within 15 min and attained peak values at 2 and 1 h, respectively. The activity of both polymerases declined almost to the control level by 4 h and then increased again with a second peak at 20 and 12 h for RNA polymerase I and II, respectively. Similarly, the template capacity of mouse kidney chromatin, as measured with mammalian RNA polymerase II, increased by 15 min, reached a peak at 1 h and returned to control level by 4 h following hormone treatment. A second dose of testosterone given at the nadir (4 h) was not capable of stimulating renal chromatin template activity significantly as compared to the effect observed after the initial hormone treatment. Contrary to the testosterone-stimulated changes in transcriptional events observed in normal female mice, androgens elicited no response in androgen-insensitive tfm/y mice, animals lacking cytosol androgen receptors. These results strongly support the contention that hormone-specific receptors are obligatory to steroid-mediated modifications in gene transcription."} {"id": "PMID:174727", "title": "Interactions of proteins and cholesterol with lipids in bilayer membranes.", "content": "Mixtures of lipids and protein, the ATPase from rabbit sarcoplasmic reticulum, were studied by freeze-fracture electron microscopy and by measurement of the amount of fluid lipid with the spin label 2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-PO). In dimyristoyl phosphatidylcholine vesicles the protein molecules were randomly distributed above the transition temperature, Tt, of the lipid and aggregated below Tt. For mixtures of dimyristoyl and dipalmitoyl phosphatidylcholine the existence of fluid and solid domains were shown in the temperature interval predicted from earlier TEMPO measurements. When protein was incorporated into this lipid mixture, freeze-fracture particles were randomly distributed in fluid lipids, or aggregated when only solid lipids were present. In mixtures of dimyristoyl phosphatidylcholine with cholesterol the protein was distributed randomly above the transition temperature of the phosphatidylcholine. Below that transition temperature the protein was excluded from a banded phase of solid lipid in the case of 10 mol% cholesterol. In mixtures containing 20 mol% cholesterol, protein molecules formed linear arrays, 50-200 nm in length, around smooth patches of lipid. Phase diagrams for lipid/cholesterol and lipid/protein systems are proposed which account for many of the available data. A model for increasing solidification of lipid around protein molecules or cholesterol above the transition temperature of the lipid is discussed.", "contents": "Interactions of proteins and cholesterol with lipids in bilayer membranes. Mixtures of lipids and protein, the ATPase from rabbit sarcoplasmic reticulum, were studied by freeze-fracture electron microscopy and by measurement of the amount of fluid lipid with the spin label 2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-PO). In dimyristoyl phosphatidylcholine vesicles the protein molecules were randomly distributed above the transition temperature, Tt, of the lipid and aggregated below Tt. For mixtures of dimyristoyl and dipalmitoyl phosphatidylcholine the existence of fluid and solid domains were shown in the temperature interval predicted from earlier TEMPO measurements. When protein was incorporated into this lipid mixture, freeze-fracture particles were randomly distributed in fluid lipids, or aggregated when only solid lipids were present. In mixtures of dimyristoyl phosphatidylcholine with cholesterol the protein was distributed randomly above the transition temperature of the phosphatidylcholine. Below that transition temperature the protein was excluded from a banded phase of solid lipid in the case of 10 mol% cholesterol. In mixtures containing 20 mol% cholesterol, protein molecules formed linear arrays, 50-200 nm in length, around smooth patches of lipid. Phase diagrams for lipid/cholesterol and lipid/protein systems are proposed which account for many of the available data. A model for increasing solidification of lipid around protein molecules or cholesterol above the transition temperature of the lipid is discussed."} {"id": "PMID:174728", "title": "Phosphorus nuclear magnetic resonance of Acholeplasma laidlawii cell membranes and derived liposomes.", "content": "1. The 129 MHz 31P-NMR spectrum of Acholeplasma laidlawii membranes is very similar to the spectrum of the derived liposomes and is a typical \"solid state\" spectrum in which the major contribution to the linewidth is made by the chemical shift anisotropy. From the value of the chemical shift anisotropy an order parameter of 0.15 is estimated for the lipid phosphates in both membranes. 2. The 31P-NMR spectrum of the A. laidlawii membrane is insensitive to pronase digestion of 4-60% of the membrane proteins and subsequent cytochrome C binding. These results indicate that either no strong lipid polar headgroup-protein interactions occur in the membrane or that the lipid-protein \"complexes\" in the membrane have a fast rotation (Tc shorter than 10(-6)S) along an axis perpendicular to the plane of the membrane. 3. Phospholipase A2 degrades all the phosphatidylglycerol in the membrane. The resulting membrane contains a phosphoglycolipid as the sole phosphorus-containing compound. The 31P-NMR spectrum of these membranes is identical to the spectrum of the native membranes suggesting a similar motion for the phosphate groups in both lipids. 4. Ca2+ binding to liposomes prepared from either the total polar lipids or the total phosphorus-containing lipids isolated from the A. laidlawii membrane does not affect the 21P-NMR spectrum. 5. The 31P-NMR spectrum of the membranes and derived liposomes, however, is sensitive to lipid phase transitions. When the membrane lipids are in the gel state a broadening of the 31P resonance occurs demonstrating that the polar head group motion in a biological membrane is more restricted below the lipid-phase transition temperature.", "contents": "Phosphorus nuclear magnetic resonance of Acholeplasma laidlawii cell membranes and derived liposomes. 1. The 129 MHz 31P-NMR spectrum of Acholeplasma laidlawii membranes is very similar to the spectrum of the derived liposomes and is a typical \"solid state\" spectrum in which the major contribution to the linewidth is made by the chemical shift anisotropy. From the value of the chemical shift anisotropy an order parameter of 0.15 is estimated for the lipid phosphates in both membranes. 2. The 31P-NMR spectrum of the A. laidlawii membrane is insensitive to pronase digestion of 4-60% of the membrane proteins and subsequent cytochrome C binding. These results indicate that either no strong lipid polar headgroup-protein interactions occur in the membrane or that the lipid-protein \"complexes\" in the membrane have a fast rotation (Tc shorter than 10(-6)S) along an axis perpendicular to the plane of the membrane. 3. Phospholipase A2 degrades all the phosphatidylglycerol in the membrane. The resulting membrane contains a phosphoglycolipid as the sole phosphorus-containing compound. The 31P-NMR spectrum of these membranes is identical to the spectrum of the native membranes suggesting a similar motion for the phosphate groups in both lipids. 4. Ca2+ binding to liposomes prepared from either the total polar lipids or the total phosphorus-containing lipids isolated from the A. laidlawii membrane does not affect the 21P-NMR spectrum. 5. The 31P-NMR spectrum of the membranes and derived liposomes, however, is sensitive to lipid phase transitions. When the membrane lipids are in the gel state a broadening of the 31P resonance occurs demonstrating that the polar head group motion in a biological membrane is more restricted below the lipid-phase transition temperature."} {"id": "PMID:174729", "title": "Comparative study of the milk fat globule membrane and the mouse mammary tumour virus prepared from the milk of an infected strain of Swiss albino mice.", "content": "Milk fat globule membranes and mammary tumour virus particles (d=1.17 g/cm3) have been obtained from the milk of a Swiss albino mice strain. Comparative biochemistry shows that these two structures differ significantly in the phospholipid, polypeptide and glycopolypeptide patterns and enzymatic activities. However, the lipid profile and the morphology of both structures suggest a filiation with the plasma membrane. Density fractions obtained from the crude virus preparation have been thoroughly investigated. The results suggest that most of these fractions represent degraded virus and/or atypical virus assembly.", "contents": "Comparative study of the milk fat globule membrane and the mouse mammary tumour virus prepared from the milk of an infected strain of Swiss albino mice. Milk fat globule membranes and mammary tumour virus particles (d=1.17 g/cm3) have been obtained from the milk of a Swiss albino mice strain. Comparative biochemistry shows that these two structures differ significantly in the phospholipid, polypeptide and glycopolypeptide patterns and enzymatic activities. However, the lipid profile and the morphology of both structures suggest a filiation with the plasma membrane. Density fractions obtained from the crude virus preparation have been thoroughly investigated. The results suggest that most of these fractions represent degraded virus and/or atypical virus assembly."} {"id": "PMID:174730", "title": "Interactions of lectins with plasma membrane glycoproteins of the Ehrlich ascites carcinoma cell.", "content": "Several aspects of the interaction of various lectins with the surface of Ehrlich ascites carcinoma cells are described. The order of agglutinating activity for various lectins is Ricinus communis greater than wheat germ greater than or equal to concanavalin A greater than or equal to soybean greater than Limulus polyphemus. No agglutination was noted for Ulex europaeus. Using 125I-labeled lectins it was determined that there are 1.6 and 7 times as many Ricinus communis lectin binding sites for concanavalin A and soybean lectins. Sodium deoxycholate-solubilized plasma membrane material was subjected to lectin affinity chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lectin receptors of the plasma membrane appeared to be heterogeneous and some qualitative differences could be discerned among the electrophoretically analyzed material, which bound to and was specifically eluted from the various lectin affinity columns. The characteristics of elution of bound material from individual lectin columns indicated secondary hydrophobic interactions between concanavalin A or wheat germ agglutinin and their respective lectin receptor molecules.", "contents": "Interactions of lectins with plasma membrane glycoproteins of the Ehrlich ascites carcinoma cell. Several aspects of the interaction of various lectins with the surface of Ehrlich ascites carcinoma cells are described. The order of agglutinating activity for various lectins is Ricinus communis greater than wheat germ greater than or equal to concanavalin A greater than or equal to soybean greater than Limulus polyphemus. No agglutination was noted for Ulex europaeus. Using 125I-labeled lectins it was determined that there are 1.6 and 7 times as many Ricinus communis lectin binding sites for concanavalin A and soybean lectins. Sodium deoxycholate-solubilized plasma membrane material was subjected to lectin affinity chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lectin receptors of the plasma membrane appeared to be heterogeneous and some qualitative differences could be discerned among the electrophoretically analyzed material, which bound to and was specifically eluted from the various lectin affinity columns. The characteristics of elution of bound material from individual lectin columns indicated secondary hydrophobic interactions between concanavalin A or wheat germ agglutinin and their respective lectin receptor molecules."} {"id": "PMID:174731", "title": "Correlation between protein kinase-mediated stimulation of calcium transport by cardiac sarcoplasmic reticulum and phosphorylation of a 22000 dalton protein.", "content": "Increases in protein kinase-catalyzed phosphorylation of a 22000 dalton protein correlated closely with increases in phosphate-facilitated calcium transport measured concurrently in canine cardiac sarcoplasmic reticulum under similar conditions in the presence of varying concentrations of bovine cardiac protein kinase. A correlation coefficient of 0.93 and a P value of less than 0.001 were obtained. Protein kinase-catalyzed phosphorylation of the 22000 dalton microsomal protein may mediate the abbreviation of systole seen in the mammalian heart in response to inotropic agents like catecholamines.", "contents": "Correlation between protein kinase-mediated stimulation of calcium transport by cardiac sarcoplasmic reticulum and phosphorylation of a 22000 dalton protein. Increases in protein kinase-catalyzed phosphorylation of a 22000 dalton protein correlated closely with increases in phosphate-facilitated calcium transport measured concurrently in canine cardiac sarcoplasmic reticulum under similar conditions in the presence of varying concentrations of bovine cardiac protein kinase. A correlation coefficient of 0.93 and a P value of less than 0.001 were obtained. Protein kinase-catalyzed phosphorylation of the 22000 dalton microsomal protein may mediate the abbreviation of systole seen in the mammalian heart in response to inotropic agents like catecholamines."} {"id": "PMID:174732", "title": "Steroid-protein interactions. XXXIV. Chemical modification of alpha1-acid glycoprotein for characterization of the progesterone binding site.", "content": "The nature of the steroid binding site in alpha1-acid glycoprotein (orosomucoid) was investigated by chemical modification of individual amino acids and subsequent examination of the binding affinity for progesterone. Equilibrium dialyses were performed under conditions that excluded contact with human skin. Reaction of the lysyl residues with trinitrobenzenesulfonic acid or arylisocyanates resulted in a reduction of active sites. In an alternate approach, one lysyl residue of alpha1-acid glycoprotein was protected from modification by trinitrobenzenesulfonic acid when progesterone was present to form the complex with alpha1-acid glycoprotein. We conclude that a lysyl residue is located in the binding site. Reaction of tetranitromethane with the tyrosine groups in alpha1-acid glycoprotein also reduced the number of active binding sites for progesterone. Again, a partial protection of this modification was seen in the presence of progesterone and other delta4-3-ketosteroids. The progesterone binding activity observed in the tyrosine-modified alpha1-acid glycoprotein by equilibrium dialysis and by fluorescence quenching titration can be interpreted best by the presence of one tyrosyl residue in the binding site, and involvement of a second tyrosine nearby. Modification of tryptophan in alpha1-acid glycoprotein by mild acid hydrolysis, N-bromosuccinimide, hydroxynitrobenzylbromide, and formic acid resulted in a decreased steroid binding; the formylation reaction was fully reversible. The approximate distance between progesterone and the tryptophan involved in the binding was calculated to be between 9.1 A and 14.1 A. When alpah1-acid glycoprotein was cleaved by the cyanogen bromide procedure according to Ikenaka et al. (1972, Biochemistry 11, 3817-3829), both the amino and the carboxyl fragment had a weak progesterone binding affinity which could be measured in 4 M NaCl. This result thus failed to specify the location of the steroid binding site in alpha1-acid glycoprotein. However, the closeness of tryptophan, lysine and tyrosine in the primary and presumably the tertiary structure of alpha1-acid glycoprotein is in agreement with the properties of the binding site suggested by our studies.", "contents": "Steroid-protein interactions. XXXIV. Chemical modification of alpha1-acid glycoprotein for characterization of the progesterone binding site. The nature of the steroid binding site in alpha1-acid glycoprotein (orosomucoid) was investigated by chemical modification of individual amino acids and subsequent examination of the binding affinity for progesterone. Equilibrium dialyses were performed under conditions that excluded contact with human skin. Reaction of the lysyl residues with trinitrobenzenesulfonic acid or arylisocyanates resulted in a reduction of active sites. In an alternate approach, one lysyl residue of alpha1-acid glycoprotein was protected from modification by trinitrobenzenesulfonic acid when progesterone was present to form the complex with alpha1-acid glycoprotein. We conclude that a lysyl residue is located in the binding site. Reaction of tetranitromethane with the tyrosine groups in alpha1-acid glycoprotein also reduced the number of active binding sites for progesterone. Again, a partial protection of this modification was seen in the presence of progesterone and other delta4-3-ketosteroids. The progesterone binding activity observed in the tyrosine-modified alpha1-acid glycoprotein by equilibrium dialysis and by fluorescence quenching titration can be interpreted best by the presence of one tyrosyl residue in the binding site, and involvement of a second tyrosine nearby. Modification of tryptophan in alpha1-acid glycoprotein by mild acid hydrolysis, N-bromosuccinimide, hydroxynitrobenzylbromide, and formic acid resulted in a decreased steroid binding; the formylation reaction was fully reversible. The approximate distance between progesterone and the tryptophan involved in the binding was calculated to be between 9.1 A and 14.1 A. When alpah1-acid glycoprotein was cleaved by the cyanogen bromide procedure according to Ikenaka et al. (1972, Biochemistry 11, 3817-3829), both the amino and the carboxyl fragment had a weak progesterone binding affinity which could be measured in 4 M NaCl. This result thus failed to specify the location of the steroid binding site in alpha1-acid glycoprotein. However, the closeness of tryptophan, lysine and tyrosine in the primary and presumably the tertiary structure of alpha1-acid glycoprotein is in agreement with the properties of the binding site suggested by our studies."} {"id": "PMID:174733", "title": "A putative glucocorticoid receptor and a transcortin-like macromolecule in pituitary cytosol.", "content": "This study describes the binding of [3H]corticosterone and [3H] dexamethasone to soluble macromolecules in the pituitaries of adrenalectomized rats perfused at sacrifice to remove blood contamination. (1) Unlabeled dexamethasone competes only slightly for [3H] corticosterone binding when the steroids are added to cytosol as well as when the steroids are present from the time of disruption of the tissue. In the latter case, corticosterone is as good a competitor as dexamethasone for [3H]dexamethasone binding. (2) Gel permeation chrmatography with BioRad A-5M reveals the presence of a [3H] corticosterone-macromolecular complex with an elution volume comparable to transcortin as well as a very large hormone-binding complex eluting in the void volume of the column...", "contents": "A putative glucocorticoid receptor and a transcortin-like macromolecule in pituitary cytosol. This study describes the binding of [3H]corticosterone and [3H] dexamethasone to soluble macromolecules in the pituitaries of adrenalectomized rats perfused at sacrifice to remove blood contamination. (1) Unlabeled dexamethasone competes only slightly for [3H] corticosterone binding when the steroids are added to cytosol as well as when the steroids are present from the time of disruption of the tissue. In the latter case, corticosterone is as good a competitor as dexamethasone for [3H]dexamethasone binding. (2) Gel permeation chrmatography with BioRad A-5M reveals the presence of a [3H] corticosterone-macromolecular complex with an elution volume comparable to transcortin as well as a very large hormone-binding complex eluting in the void volume of the column..."} {"id": "PMID:174734", "title": "Hepatic accumulation of vitamin D3 and 25-hydroxyvitamin D3.", "content": "Concomitant intravenous administration of 25-hydroxycholecalciferol and [3H] vitamin D3 to vitamin D-depleted rats did not affect the conversion of [3H] vitamin D3 to 25-OH-[3H] vitamin D3 as indicated by a serum 25-OH-[3H] vitamin D3 to content at 3 and 24 h identical to those observed in animals receiving [3H] vitamin D3 alone. Similarly, pre-dosing with 25-OH vitamin D3 24 h earlier did not affect the conversion. Co-administration to vitamin D depleted rats of vitamin D2 or D3, at 200-fold higher doses than a control group receiving tracer [3H] vitamin D3 alone, resulted in serum 25-OH vitamin D levels that were 15-20 fold higher than the control, indicating a similar metabolic fate for synthetic and natural vitamin D in rats and the ability of increased substrate to overwhelm hepatic constraints on 25-OH vitamin D production. Following intravenous administration of 25-OH-[3H] vitamin D3 to vitamin D depleted rats, hepatic 3H content decreased in parallel with serum radioactivity. Hepatic accumulation of intravenously administered vitamin D3 ([14C] vitamin D3) alone or with 25-OH-[3H] vitamin D3, by vitamin D-depleted rats revealed a marked preference for vitamin D3; the hepatic accumulation of [14C] vitamin D3 increased to 35% of the dose by 45 min, at which time 25-OH-[3H] vitamin D3 hepatic content was 7-fold less, and decreasing. Chromatography of extracts of hepatic subcellular fractions revealed more [14C] vitamin D3 than 25-OH-[3H] vitamin D3 in the microsomes, the reported site of calciferol 25-hydroxylase. Circulating 25-OH vitamin D, therefore, has comparatively minimal potential for hepatic accumulation. Product inhibition of the calciferol 25-hydroxylase must, therefore, result from recently synthesized hepatic 25-OH vitamin D, and is not affected by exogenous 25-OH vitamin D3.", "contents": "Hepatic accumulation of vitamin D3 and 25-hydroxyvitamin D3. Concomitant intravenous administration of 25-hydroxycholecalciferol and [3H] vitamin D3 to vitamin D-depleted rats did not affect the conversion of [3H] vitamin D3 to 25-OH-[3H] vitamin D3 as indicated by a serum 25-OH-[3H] vitamin D3 to content at 3 and 24 h identical to those observed in animals receiving [3H] vitamin D3 alone. Similarly, pre-dosing with 25-OH vitamin D3 24 h earlier did not affect the conversion. Co-administration to vitamin D depleted rats of vitamin D2 or D3, at 200-fold higher doses than a control group receiving tracer [3H] vitamin D3 alone, resulted in serum 25-OH vitamin D levels that were 15-20 fold higher than the control, indicating a similar metabolic fate for synthetic and natural vitamin D in rats and the ability of increased substrate to overwhelm hepatic constraints on 25-OH vitamin D production. Following intravenous administration of 25-OH-[3H] vitamin D3 to vitamin D depleted rats, hepatic 3H content decreased in parallel with serum radioactivity. Hepatic accumulation of intravenously administered vitamin D3 ([14C] vitamin D3) alone or with 25-OH-[3H] vitamin D3, by vitamin D-depleted rats revealed a marked preference for vitamin D3; the hepatic accumulation of [14C] vitamin D3 increased to 35% of the dose by 45 min, at which time 25-OH-[3H] vitamin D3 hepatic content was 7-fold less, and decreasing. Chromatography of extracts of hepatic subcellular fractions revealed more [14C] vitamin D3 than 25-OH-[3H] vitamin D3 in the microsomes, the reported site of calciferol 25-hydroxylase. Circulating 25-OH vitamin D, therefore, has comparatively minimal potential for hepatic accumulation. Product inhibition of the calciferol 25-hydroxylase must, therefore, result from recently synthesized hepatic 25-OH vitamin D, and is not affected by exogenous 25-OH vitamin D3."} {"id": "PMID:174735", "title": "Differences between cytosol receptor complexes with corticosterone and dexamethasone in hippocampal tissue from rat brain.", "content": "The binding of [3H]corticosterone and [3H]dexamethasone to soluble macromolecules in cytosol of the hippocampal region of the brain has been studied in adrenalectomized male rats. Unlabeled dexamethasone appears to be a less effective competitor than corticosterone in the binding of [3H]corticosterone, while both unlabeled steroids compete equally well for the binding or [3H]dexamethasone. Further investigation of macromolecular complexes with [3H]dexamethasone and [3H]corticosterone revealed that they differ from each other in their behavior during ammonium sulfate precipitation, BioRad A-5M gel permeation chromatography, DE-52 anion exchange chromatography and DNA-cellulose chromatography. (1) After exposure to a 33% ammonium sulfate solution relatively more [3H]dexamethasone complex than [3H]corticosterone complex is precipitated. (2) Treatment of the cytosol with 0.3 M KCl gives disaggregation of the supramolecular 3H-labeled corticoid complexes which are seen eluting with the void volume during gel permeation chromatography on Biorad A-5M at low ionic strength. In 0.3 M KCl, the [3H]dexamethasone complex has an elution volume somewhat smaller than that of bovine serum albumin, while the [3H]-corticosterone complex in 0.3 M KCl is too unstable to survive chromatography with A-5M. (3) Chromatography on DE-52 resolved the 3H-labeled corticoid complexes into three binding components. The complex with [3H]dexamethasone contains a higher percentage (85%) of a component less firmly attached (i.e. eluted by 0.15 M KCl) to the anion exchange resin than is observed for the complex with [3H]corticosterone (49%). (4) The complexes with 3H-labeled corticoids display an enhanced affinity for calf thymus DNA adsorbed to cellulose following \"activation\", warming to 25 degrees C for 15 min. Concurrently, a fraction of the [3H]dexamethasone complex becomes able to more firmly attach to the DE-52 anion exchange resin. These results with the binding of the cytosol hormone-receptor complexes to DNA-cellulose do not explain the marked in vivo preference of hippocampus for the cell nuclear uptake of [3H] corticosterone. However, the other differences in the properties of the complexes formed with the two labeled glucocorticoids support our previous inference that there may be more than one population of adrenal steroid \"receptors\" in brain tissue.", "contents": "Differences between cytosol receptor complexes with corticosterone and dexamethasone in hippocampal tissue from rat brain. The binding of [3H]corticosterone and [3H]dexamethasone to soluble macromolecules in cytosol of the hippocampal region of the brain has been studied in adrenalectomized male rats. Unlabeled dexamethasone appears to be a less effective competitor than corticosterone in the binding of [3H]corticosterone, while both unlabeled steroids compete equally well for the binding or [3H]dexamethasone. Further investigation of macromolecular complexes with [3H]dexamethasone and [3H]corticosterone revealed that they differ from each other in their behavior during ammonium sulfate precipitation, BioRad A-5M gel permeation chromatography, DE-52 anion exchange chromatography and DNA-cellulose chromatography. (1) After exposure to a 33% ammonium sulfate solution relatively more [3H]dexamethasone complex than [3H]corticosterone complex is precipitated. (2) Treatment of the cytosol with 0.3 M KCl gives disaggregation of the supramolecular 3H-labeled corticoid complexes which are seen eluting with the void volume during gel permeation chromatography on Biorad A-5M at low ionic strength. In 0.3 M KCl, the [3H]dexamethasone complex has an elution volume somewhat smaller than that of bovine serum albumin, while the [3H]-corticosterone complex in 0.3 M KCl is too unstable to survive chromatography with A-5M. (3) Chromatography on DE-52 resolved the 3H-labeled corticoid complexes into three binding components. The complex with [3H]dexamethasone contains a higher percentage (85%) of a component less firmly attached (i.e. eluted by 0.15 M KCl) to the anion exchange resin than is observed for the complex with [3H]corticosterone (49%). (4) The complexes with 3H-labeled corticoids display an enhanced affinity for calf thymus DNA adsorbed to cellulose following \"activation\", warming to 25 degrees C for 15 min. Concurrently, a fraction of the [3H]dexamethasone complex becomes able to more firmly attach to the DE-52 anion exchange resin. These results with the binding of the cytosol hormone-receptor complexes to DNA-cellulose do not explain the marked in vivo preference of hippocampus for the cell nuclear uptake of [3H] corticosterone. However, the other differences in the properties of the complexes formed with the two labeled glucocorticoids support our previous inference that there may be more than one population of adrenal steroid \"receptors\" in brain tissue."} {"id": "PMID:174736", "title": "Catecholamine secretion by isolated adrenal cells.", "content": "Isolated adrenal cells were prepared by collagenase digestion of guinea pig adrenal glands. Acetylcholine stimulates the secretion of catecholamines by these isolated adrenal cells. Acetylcholine-stimulated catecholamine secretion is inhibited by cholinergic blocking agents (atropine and hexamethonium) and by local anaesthetics (tetracaine), and is dependent upon the concentration of Ca2+ in the incubation medium. In the presence of Ca2+, catecholamine secretion is also stimulated by two divalent cation ionophores, A23187 and X-537A. Cyclic nucleotides and 5'-nucleotides cause a small, non-specific stimulation of catecholamine secretion. These results indicate that isolated adrenal cells are a useful system in which to study catecholamine secretion, and support the hypothesis that increased Ca2+ entry into chromaffin cells is a sufficient stimulus for catecholamine secretion.", "contents": "Catecholamine secretion by isolated adrenal cells. Isolated adrenal cells were prepared by collagenase digestion of guinea pig adrenal glands. Acetylcholine stimulates the secretion of catecholamines by these isolated adrenal cells. Acetylcholine-stimulated catecholamine secretion is inhibited by cholinergic blocking agents (atropine and hexamethonium) and by local anaesthetics (tetracaine), and is dependent upon the concentration of Ca2+ in the incubation medium. In the presence of Ca2+, catecholamine secretion is also stimulated by two divalent cation ionophores, A23187 and X-537A. Cyclic nucleotides and 5'-nucleotides cause a small, non-specific stimulation of catecholamine secretion. These results indicate that isolated adrenal cells are a useful system in which to study catecholamine secretion, and support the hypothesis that increased Ca2+ entry into chromaffin cells is a sufficient stimulus for catecholamine secretion."} {"id": "PMID:174737", "title": "The separation of partially modified lactate dehydrogenase by affinity chromatography. The specific activity of protomers?", "content": "Pig heart lactate dehydrogenase (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) was partially inactivated by reaction with phenylmaleimide. The resulting protein mixture was separated by affinity chromatography on a Sepharose-linked oxamate column yielding three distinct enzyme fractions with one, two and three out of four subunits being modified. The specific activities of these samples were lower than expected from the degree of modification, while the maximum binding capacity of NADH-oxamate related well to the number of catalytic centers modified. A possible cooperative effect in the native enzyme is discussed.", "contents": "The separation of partially modified lactate dehydrogenase by affinity chromatography. The specific activity of protomers? Pig heart lactate dehydrogenase (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) was partially inactivated by reaction with phenylmaleimide. The resulting protein mixture was separated by affinity chromatography on a Sepharose-linked oxamate column yielding three distinct enzyme fractions with one, two and three out of four subunits being modified. The specific activities of these samples were lower than expected from the degree of modification, while the maximum binding capacity of NADH-oxamate related well to the number of catalytic centers modified. A possible cooperative effect in the native enzyme is discussed."} {"id": "PMID:174738", "title": "Kinetic studies on the reaction catalyzed by polynucleotide kinase from phage T4-infected Escherichia coli.", "content": "Kinetic properties of polynucleotide kinase (EC 2.7.1.78) isolated from Escherichia coli cells infected with phage T4 were investigated. The reaction depends on the concentration of MgATP, while free ATP or free Mg2+ have neither inhibitory nor accelerating effect. The initial reaction velocity was plotted against variable concentrations of ATP as the phosphate donor at various fixed concentrations of 5'-hydroxyl-DNA or -oligo(rA) as the phosphate acceptor in the presence or absence of products. The double reciprocal plot analysis of the data suggested that the reaction obeys the random sequential mechanism. Various constants were determined and the reaction mechanism was discussed.", "contents": "Kinetic studies on the reaction catalyzed by polynucleotide kinase from phage T4-infected Escherichia coli. Kinetic properties of polynucleotide kinase (EC 2.7.1.78) isolated from Escherichia coli cells infected with phage T4 were investigated. The reaction depends on the concentration of MgATP, while free ATP or free Mg2+ have neither inhibitory nor accelerating effect. The initial reaction velocity was plotted against variable concentrations of ATP as the phosphate donor at various fixed concentrations of 5'-hydroxyl-DNA or -oligo(rA) as the phosphate acceptor in the presence or absence of products. The double reciprocal plot analysis of the data suggested that the reaction obeys the random sequential mechanism. Various constants were determined and the reaction mechanism was discussed."} {"id": "PMID:174739", "title": "Adenosine cyclic 3',5'-monophosphate-dependent protein kinase from human platelets.", "content": "A single cyclic AMP-dependent protein kinase (EC 2.7.1.37) has been isolated from human platelets by using DEAE-cellulose ion-exchange chromatography and Sephadex G-150 gel filtration. The molecular weight of the protein kinase was estimated to be 86 490. In the presence of cyclic AMP, the protein kinase could be dissociated into a catalytic subunit of molecular weight 50 000, and either one regulatory subunit of molecular weight 110 000 or two regulatory subunits of molecular weights 110 000 and 38 100, depending on the pH used. Recombination of either of the regulatory subunits with the catalytic subunit restored cyclic AMP-dependency in the catalytic subunit. The apparent Km for ATP in the presence of 10 muM Mg2+ was 4 muM (plus cyclic AMP) and 4.3 muM (minus cyclic AMP). The concentration of cyclic AMP needed for half-maximal stimulation of the protein kinase was 0.172 muM and apparent dissociation constants of 3.7 nM (absence of MgATP) and 0.18 muM (presence of MgATP) were exhibited by the \"protein kinase-cyclic AMP complex\". The enzyme required Mg2+ for maximum activity and showed a pH optimum of 6.2 with histone as substrate. In addition to four major endogenous platelet protein acceptors of apparent molecular weights 45 000, 28000, 18 500, and 11 100, the platelet protein kinase also phosphorylated the exogenous acceptor proteins thrombin, collagen and histone, all capable of inducing platelet aggregation. Prothrombin, a nonaggregating agent, was not phosphorylated.", "contents": "Adenosine cyclic 3',5'-monophosphate-dependent protein kinase from human platelets. A single cyclic AMP-dependent protein kinase (EC 2.7.1.37) has been isolated from human platelets by using DEAE-cellulose ion-exchange chromatography and Sephadex G-150 gel filtration. The molecular weight of the protein kinase was estimated to be 86 490. In the presence of cyclic AMP, the protein kinase could be dissociated into a catalytic subunit of molecular weight 50 000, and either one regulatory subunit of molecular weight 110 000 or two regulatory subunits of molecular weights 110 000 and 38 100, depending on the pH used. Recombination of either of the regulatory subunits with the catalytic subunit restored cyclic AMP-dependency in the catalytic subunit. The apparent Km for ATP in the presence of 10 muM Mg2+ was 4 muM (plus cyclic AMP) and 4.3 muM (minus cyclic AMP). The concentration of cyclic AMP needed for half-maximal stimulation of the protein kinase was 0.172 muM and apparent dissociation constants of 3.7 nM (absence of MgATP) and 0.18 muM (presence of MgATP) were exhibited by the \"protein kinase-cyclic AMP complex\". The enzyme required Mg2+ for maximum activity and showed a pH optimum of 6.2 with histone as substrate. In addition to four major endogenous platelet protein acceptors of apparent molecular weights 45 000, 28000, 18 500, and 11 100, the platelet protein kinase also phosphorylated the exogenous acceptor proteins thrombin, collagen and histone, all capable of inducing platelet aggregation. Prothrombin, a nonaggregating agent, was not phosphorylated."} {"id": "PMID:174740", "title": "Regulation in vitro of rat liver pyruvate kinase by phosphorylation-dephosphorylation reactions, catalyzed by cyclic-AMP dependent protein kinases and a histone phosphatase.", "content": "1. Cyclic-AMP dependent protein kinases, resolved by chromatography on DEAE-cellulose and hydroxylapatite, catalysed the phosphorylation of rat liver pyruvate kinase and calf thymus histones by [gamma32P]ATP. [32P]phosphopeptides, from acid hydrolysates of pyruvate kinase phosphorylated by the different protein kinase fractions, displayed identical electrophoretic patterns. Phosphorylation inhibited pyruvate kinase activity. 2. Full activity was restored when phosphorylated pyruvate kinase was dephosphorylated by a histone phosphatase from the soluble fraction of rat liver. These results are consistent with the hypothesis that pyruvate kinase is regulated by phosphorylation-dephosphorylation reactions.", "contents": "Regulation in vitro of rat liver pyruvate kinase by phosphorylation-dephosphorylation reactions, catalyzed by cyclic-AMP dependent protein kinases and a histone phosphatase. 1. Cyclic-AMP dependent protein kinases, resolved by chromatography on DEAE-cellulose and hydroxylapatite, catalysed the phosphorylation of rat liver pyruvate kinase and calf thymus histones by [gamma32P]ATP. [32P]phosphopeptides, from acid hydrolysates of pyruvate kinase phosphorylated by the different protein kinase fractions, displayed identical electrophoretic patterns. Phosphorylation inhibited pyruvate kinase activity. 2. Full activity was restored when phosphorylated pyruvate kinase was dephosphorylated by a histone phosphatase from the soluble fraction of rat liver. These results are consistent with the hypothesis that pyruvate kinase is regulated by phosphorylation-dephosphorylation reactions."} {"id": "PMID:174741", "title": "Demonstration of insulin degradation by thiol-protein disulfide oxidoreductase (glutathione-insulin transhydrogenase) and proteinases of pancreatic islets.", "content": "Homogenate preparations of pancreatic islets have been found to degrade insulin by cleavage of the interchain disulfide bonds, followed by proteolysis of the resulting A and B chains. A proteolytic system of the pancreatic islets splitting not only 125I-labeled insulin A chain but also 125I-labeled glucagon at pH 7.0, was shown to be activated by glutathione and inhibited by EDTA. The results suggest that pancreatic islets contain both the thiol-protein disulfide oxidoreductase (glutathione : protein-disulfide oxidoreductase, EC 1.8.4.2) and the A and B chain-degrading enzyme(s). The effects of EDTA argue against the implication of cathepsins in insulin breakdown under the experimental conditions employed.", "contents": "Demonstration of insulin degradation by thiol-protein disulfide oxidoreductase (glutathione-insulin transhydrogenase) and proteinases of pancreatic islets. Homogenate preparations of pancreatic islets have been found to degrade insulin by cleavage of the interchain disulfide bonds, followed by proteolysis of the resulting A and B chains. A proteolytic system of the pancreatic islets splitting not only 125I-labeled insulin A chain but also 125I-labeled glucagon at pH 7.0, was shown to be activated by glutathione and inhibited by EDTA. The results suggest that pancreatic islets contain both the thiol-protein disulfide oxidoreductase (glutathione : protein-disulfide oxidoreductase, EC 1.8.4.2) and the A and B chain-degrading enzyme(s). The effects of EDTA argue against the implication of cathepsins in insulin breakdown under the experimental conditions employed."} {"id": "PMID:174742", "title": "EPR signals from cytochrome c oxidase.", "content": "1. The major EPR signals from native and cytochrome c-reduced beef heart cytochrome c oxidase (EC 1.9.3.1) are characterized with respect to resonance parameters, number of components and total integrated intensity. A mistake in all earlier integrations and simulations of very anisotropic EPR signals is pointed out. 2. The so-called Cu2+ signal is found to contain at least three components, one \"inactive\" form and two nearly similar active forms. One of the latter forms, corresponding to about 20% of the total EPR detectable Cu, has not been observed earlier and can only be resolved in 35 GHz spectra. It is not reduced by cytochrome c and is thought to reflect some kind of inhomogeneity in the enzyme preparation. The 35 GHz spectrum of the cytochrome c reducible component shows a rhombic splitting and can be well simulated with g-values 2.18, 2.03 and 1.99. The origin of such a unique type of Cu2+ spectrum is discussed. 3. The low-spin heme signal in the oxidized enzyme (g = 3.03, 2.21, 1.45) is found to correspond closely to one heme and shows no signs of interaction with other paramagnetic centres. 4. The high-spin heme signals appearing in partly reduced oxidase are found to consist of at least three species, one axial and two rhombic types. An integration procedure is described that allows the determination of the total integral intensity of high-spin heme EPR signals only by considering the g = 6 part of the signals. In a titration with ascorbate and cytochrome c the maximum intensity of the g = 6 species corresponds to 23% of the enzyme concentration.", "contents": "EPR signals from cytochrome c oxidase. 1. The major EPR signals from native and cytochrome c-reduced beef heart cytochrome c oxidase (EC 1.9.3.1) are characterized with respect to resonance parameters, number of components and total integrated intensity. A mistake in all earlier integrations and simulations of very anisotropic EPR signals is pointed out. 2. The so-called Cu2+ signal is found to contain at least three components, one \"inactive\" form and two nearly similar active forms. One of the latter forms, corresponding to about 20% of the total EPR detectable Cu, has not been observed earlier and can only be resolved in 35 GHz spectra. It is not reduced by cytochrome c and is thought to reflect some kind of inhomogeneity in the enzyme preparation. The 35 GHz spectrum of the cytochrome c reducible component shows a rhombic splitting and can be well simulated with g-values 2.18, 2.03 and 1.99. The origin of such a unique type of Cu2+ spectrum is discussed. 3. The low-spin heme signal in the oxidized enzyme (g = 3.03, 2.21, 1.45) is found to correspond closely to one heme and shows no signs of interaction with other paramagnetic centres. 4. The high-spin heme signals appearing in partly reduced oxidase are found to consist of at least three species, one axial and two rhombic types. An integration procedure is described that allows the determination of the total integral intensity of high-spin heme EPR signals only by considering the g = 6 part of the signals. In a titration with ascorbate and cytochrome c the maximum intensity of the g = 6 species corresponds to 23% of the enzyme concentration."} {"id": "PMID:174743", "title": "Influence of the carbon source on glycerol kinase activity in Neurospora crassa.", "content": "The level of glycerol kinase activity in Neurospora crassa was shown to change in response to resuspension of sucrose-grown mycelia in fresh medium containing a new carbon source: the magnitude of the change depended on the new carbon source provided. Certain carbon sources, such as glucose and fructose, inhibited the small increase that occurred in the absence of any carbon source. Others, and in particular deoxyribose, galactose, glycerol and ribose, greatly enhanced this increase. The activity induced by deoxyribose and galactose had the same stability, both in vivo and in vitro, as that induced by glycerol, and as that induced by incubation of Neurospora cultures at low temperatures. The inhibitory carbon sources, such as glucose and fructose, also restricted the increases induced by deoxyribose, galactose and glycerol: they had more effect on the increases induced by glycerol and deoxyribose than on that induced by galactose. The increase in activity that occurs at low temperature was also inhibited by glucose and sucrose.", "contents": "Influence of the carbon source on glycerol kinase activity in Neurospora crassa. The level of glycerol kinase activity in Neurospora crassa was shown to change in response to resuspension of sucrose-grown mycelia in fresh medium containing a new carbon source: the magnitude of the change depended on the new carbon source provided. Certain carbon sources, such as glucose and fructose, inhibited the small increase that occurred in the absence of any carbon source. Others, and in particular deoxyribose, galactose, glycerol and ribose, greatly enhanced this increase. The activity induced by deoxyribose and galactose had the same stability, both in vivo and in vitro, as that induced by glycerol, and as that induced by incubation of Neurospora cultures at low temperatures. The inhibitory carbon sources, such as glucose and fructose, also restricted the increases induced by deoxyribose, galactose and glycerol: they had more effect on the increases induced by glycerol and deoxyribose than on that induced by galactose. The increase in activity that occurs at low temperature was also inhibited by glucose and sucrose."} {"id": "PMID:174744", "title": "A kinetic analysis of the cyclic nucleotide phosphodiesterase regulation by the endogenous protein activator. A study of rat brain and frog sympathetic chain.", "content": "The effect of the endogenous protein activator on the kinetic characteristics of a highly purified, activator-deficient rat brain phosphodiesterase (EC 3.1.4.-) of a highly purified, activator-deficient rat brain phosphodiesterase (EC 3.1.4-) was studied. This enzyme preparation has only a high Km for cyclic AMP and a low Km for cyclic GMP. In the presence of 20 muM Ca2+, saturating concentrations of the activator decreased the Km of this enzyme for cyclic AMP from 350 muM to about 80 muM, without changing the V. The phosphodiesterase activator did not change the Km of phosphodiesterase for cyclic GMP; however, amoderate increase of V was seen. The activator lacks species specificity; the activator isolated from the bullfrog sympathetic chain produced the same qualitative and comparable quantitative changes in the kinetic properties of the purified rat brain phosphodiesterase. Cyclic GMP is a potent competitive inhibitor of the phosphodiesterase activation by the activator (Ki=1.8 muM), using cyclic AMP as a substrate. Cyclic AMP inhibits slightly the hydrolysis of cyclic GMP by phosphodiesterase in the presence of activator (Ki=155 muM) only.", "contents": "A kinetic analysis of the cyclic nucleotide phosphodiesterase regulation by the endogenous protein activator. A study of rat brain and frog sympathetic chain. The effect of the endogenous protein activator on the kinetic characteristics of a highly purified, activator-deficient rat brain phosphodiesterase (EC 3.1.4.-) of a highly purified, activator-deficient rat brain phosphodiesterase (EC 3.1.4-) was studied. This enzyme preparation has only a high Km for cyclic AMP and a low Km for cyclic GMP. In the presence of 20 muM Ca2+, saturating concentrations of the activator decreased the Km of this enzyme for cyclic AMP from 350 muM to about 80 muM, without changing the V. The phosphodiesterase activator did not change the Km of phosphodiesterase for cyclic GMP; however, amoderate increase of V was seen. The activator lacks species specificity; the activator isolated from the bullfrog sympathetic chain produced the same qualitative and comparable quantitative changes in the kinetic properties of the purified rat brain phosphodiesterase. Cyclic GMP is a potent competitive inhibitor of the phosphodiesterase activation by the activator (Ki=1.8 muM), using cyclic AMP as a substrate. Cyclic AMP inhibits slightly the hydrolysis of cyclic GMP by phosphodiesterase in the presence of activator (Ki=155 muM) only."} {"id": "PMID:174745", "title": "Proteolysis of canine apolipoprotein by acid proteases in canine liver lysosomes.", "content": "Canine liver lysosomes were purified by sucrose discontinuous density gradient centrifugation and then ruptured by sonication to obtain the soluble fraction. This soluble lysosomal fraction, which contained a 25-fold increase in acid phosphatase activity per mg of total protein when compared with the original homogenate, was incubated with a subfraction (1.110 less than d less than 1.210 g/cm3, HDL3) of canine high density lipoproteins (HDL) at pH 3.8. HDL3 proteolysis by lysosomal proteases, measured as the release of peptides and amino acids by the ninhydrin reaction, followed hyperbolic curves with straight lines (r = 0.99) obtained on Lineweaver-Burk plots. Km calculated from the Lineweaver-Burk plot was 635 mug of HDL3 protein per 0.5 ml of incubation mixture. Optimum HDL3 proteolysis was observed from pH 3.8 to 4.5. Incubation with the other subcellular organelle fractions did not result in HDL3 proteolysis. To evaluate the effects of enzyme inhibitors, iodoacetate, p-chloromercuribenzoate (both specific for the endopeptidase, cathepsin B (EC 3.4.22.1)) and pepstatin (specific for the endopeptidase, cathepsin D (EC 3.4.23.5) were tested. Iodoacetate and p-chloromercuribenzoate inhibited HDL3 proteolysis 100% and bovine serum albumin proteolysis 65%. Pepstatin inhibited HDL3 proteolysis 45% and bovine serum albumin proteolysis 70%. The in vitro data presented support the hypothesis that hepatic lysosomes play an important role in HDL3 catabolism in the dog. Furthermore, results obtained from enzyme inhibition studies suggest that a specific lysosomal endopeptidase, cathepsin B, may play the key role in HDL3 proteolysis.", "contents": "Proteolysis of canine apolipoprotein by acid proteases in canine liver lysosomes. Canine liver lysosomes were purified by sucrose discontinuous density gradient centrifugation and then ruptured by sonication to obtain the soluble fraction. This soluble lysosomal fraction, which contained a 25-fold increase in acid phosphatase activity per mg of total protein when compared with the original homogenate, was incubated with a subfraction (1.110 less than d less than 1.210 g/cm3, HDL3) of canine high density lipoproteins (HDL) at pH 3.8. HDL3 proteolysis by lysosomal proteases, measured as the release of peptides and amino acids by the ninhydrin reaction, followed hyperbolic curves with straight lines (r = 0.99) obtained on Lineweaver-Burk plots. Km calculated from the Lineweaver-Burk plot was 635 mug of HDL3 protein per 0.5 ml of incubation mixture. Optimum HDL3 proteolysis was observed from pH 3.8 to 4.5. Incubation with the other subcellular organelle fractions did not result in HDL3 proteolysis. To evaluate the effects of enzyme inhibitors, iodoacetate, p-chloromercuribenzoate (both specific for the endopeptidase, cathepsin B (EC 3.4.22.1)) and pepstatin (specific for the endopeptidase, cathepsin D (EC 3.4.23.5) were tested. Iodoacetate and p-chloromercuribenzoate inhibited HDL3 proteolysis 100% and bovine serum albumin proteolysis 65%. Pepstatin inhibited HDL3 proteolysis 45% and bovine serum albumin proteolysis 70%. The in vitro data presented support the hypothesis that hepatic lysosomes play an important role in HDL3 catabolism in the dog. Furthermore, results obtained from enzyme inhibition studies suggest that a specific lysosomal endopeptidase, cathepsin B, may play the key role in HDL3 proteolysis."} {"id": "PMID:174746", "title": "Photochemical activities of reaction centers from Rhodopseudomonas sphaeroides at low temperature and in the presence of chaotropic agents.", "content": "Light-induced absorbance changes were measured at low temperatures in reaction center preparations from Rhodopseudomonas sphaeroides. Absorbance difference spectra measured at 100 degrees K show that ubiquinone is photoreduced at this temperature, both by continuous light and by a short actinic flash. The reduction occurred with relatively high efficiency. These results give support to the idea that ubiquinone is involved in the primary photochemical reaction in Rhodopseudomonas sphaeroides. Reduction of ubiquinone was accompanied by a shift of the infrared absorption band of bacteriopheophytin. The rate of decay of the primary photoproducts (P+870 and ubisemiquinone) appeared to be approximately independent of temperature below 180 degrees K and above 270 degrees K; in the region between 180 and 270 degrees K it increased with decreasing temperature. The rate of decay was not affected by 0-phenanthroline. Secondary reactions were inhibited by lowering the temperature. The light-induced absorbance changes were inhibited by chaotropic agents, like thiocyanate and perchlorate. It was concluded that these agents lower the efficiency of the primary photoconversion. The kinetics indicated that the degree of inhibition was not the same for all reaction centers. The absorption spectrum of the photoconverted reaction centers appeared to be somewhat modified by thiocyanate.", "contents": "Photochemical activities of reaction centers from Rhodopseudomonas sphaeroides at low temperature and in the presence of chaotropic agents. Light-induced absorbance changes were measured at low temperatures in reaction center preparations from Rhodopseudomonas sphaeroides. Absorbance difference spectra measured at 100 degrees K show that ubiquinone is photoreduced at this temperature, both by continuous light and by a short actinic flash. The reduction occurred with relatively high efficiency. These results give support to the idea that ubiquinone is involved in the primary photochemical reaction in Rhodopseudomonas sphaeroides. Reduction of ubiquinone was accompanied by a shift of the infrared absorption band of bacteriopheophytin. The rate of decay of the primary photoproducts (P+870 and ubisemiquinone) appeared to be approximately independent of temperature below 180 degrees K and above 270 degrees K; in the region between 180 and 270 degrees K it increased with decreasing temperature. The rate of decay was not affected by 0-phenanthroline. Secondary reactions were inhibited by lowering the temperature. The light-induced absorbance changes were inhibited by chaotropic agents, like thiocyanate and perchlorate. It was concluded that these agents lower the efficiency of the primary photoconversion. The kinetics indicated that the degree of inhibition was not the same for all reaction centers. The absorption spectrum of the photoconverted reaction centers appeared to be somewhat modified by thiocyanate."} {"id": "PMID:174747", "title": "Oxido-reductive titrations of cytochrome c oxidase followed by EPR spectroscopy.", "content": "Experiments are described on oxido-reductive titrations of cytochrome c oxidase as followed by low-temperature EPR and reflectance spectroscopy. The reductants were cytochrome c or NADH and the oxidant ferricyanide. Experiments were conducted in the presence and absence of either cytochrome c or carbon monoxide, or both. An attempt is made to provide a complete quantitative balance of the changes observed in the major EPR signals. During reduction, the maximal quantity of heme represented in the high-spin ferric heme signals (g approximately 6; 2) is 25% of the total heme present, and during reoxidation 30%. With NADH reduction there is little difference between the pattern of disappearance of the low-spin ferric heme signals in the absence or presence of cytochrome c. The copper and high-spin heme signals, however, disappear at higher titrant concentrations in the presence of cytochrome c than in its absence. In these titrations, as well as in those with ferrocytochrome c, the quantitative balance indicates that, in addition to EPR-detectable components, EPR-undetectable components are also reduced, increasingly so at higher titrant concentrations. The quantity of EPR-undectable components reduced appears to be inverely related to pH. A similar inverse relationship exists between pH and appearance of high-spin signals during yhe titration. At pH 9.3 the quantity of heme represented in the high-spin signals is less than 5%, whereas it approximately doubles from pH 7.4 to pH 6.1. In the presence of CO less of the low-spin heme and copper signals disappears for the same quantity of titrant consumed, again implying reduction of EPR undetectable components. At least one of these components is represented in a broad absorption band centered at 655 nm. The stoichiometry observed on reoxidation, particularly in the presence of CO, is not compatible with the notion that the copper signal represents 100% of the active copper of the enzyme as a pair of interacting copper atoms.", "contents": "Oxido-reductive titrations of cytochrome c oxidase followed by EPR spectroscopy. Experiments are described on oxido-reductive titrations of cytochrome c oxidase as followed by low-temperature EPR and reflectance spectroscopy. The reductants were cytochrome c or NADH and the oxidant ferricyanide. Experiments were conducted in the presence and absence of either cytochrome c or carbon monoxide, or both. An attempt is made to provide a complete quantitative balance of the changes observed in the major EPR signals. During reduction, the maximal quantity of heme represented in the high-spin ferric heme signals (g approximately 6; 2) is 25% of the total heme present, and during reoxidation 30%. With NADH reduction there is little difference between the pattern of disappearance of the low-spin ferric heme signals in the absence or presence of cytochrome c. The copper and high-spin heme signals, however, disappear at higher titrant concentrations in the presence of cytochrome c than in its absence. In these titrations, as well as in those with ferrocytochrome c, the quantitative balance indicates that, in addition to EPR-detectable components, EPR-undetectable components are also reduced, increasingly so at higher titrant concentrations. The quantity of EPR-undectable components reduced appears to be inverely related to pH. A similar inverse relationship exists between pH and appearance of high-spin signals during yhe titration. At pH 9.3 the quantity of heme represented in the high-spin signals is less than 5%, whereas it approximately doubles from pH 7.4 to pH 6.1. In the presence of CO less of the low-spin heme and copper signals disappears for the same quantity of titrant consumed, again implying reduction of EPR undetectable components. At least one of these components is represented in a broad absorption band centered at 655 nm. The stoichiometry observed on reoxidation, particularly in the presence of CO, is not compatible with the notion that the copper signal represents 100% of the active copper of the enzyme as a pair of interacting copper atoms."} {"id": "PMID:174748", "title": "Regulation of penicillin acylase in Escherichia coli by cyclic AMP.", "content": "1. Cyclic AMP was found to stimulate penicillin acylase activity. 2. It also overcame the repression of glucose and restored enzyme synthesis to the non-repressed levels. 3. The conversion of inactive enzyme precursor into active enzyme was not stimulated by cyclic AMP in cells in which protein synthesis was inhibited by chloramphenicol. 4. Cyclic AMP failed to stimulate enzyme production in cells in which messenger RNA synthesis was arrested by rifampicin or inducer removal. 5. Cyclic AMP appears to participate in the regulation of this enzyme at the transcriptional level.", "contents": "Regulation of penicillin acylase in Escherichia coli by cyclic AMP. 1. Cyclic AMP was found to stimulate penicillin acylase activity. 2. It also overcame the repression of glucose and restored enzyme synthesis to the non-repressed levels. 3. The conversion of inactive enzyme precursor into active enzyme was not stimulated by cyclic AMP in cells in which protein synthesis was inhibited by chloramphenicol. 4. Cyclic AMP failed to stimulate enzyme production in cells in which messenger RNA synthesis was arrested by rifampicin or inducer removal. 5. Cyclic AMP appears to participate in the regulation of this enzyme at the transcriptional level."} {"id": "PMID:174749", "title": "Base composition studies on mitochondrial 4 S RNA from rat liver and Morris hepatomas 5123D and 7777.", "content": "The major and modified base composition of mitochondrial 4 S RNA from rat liver and from Morris hepatomas 5123D and 7777 has been determined for 16 constituents using a chemical tritium-derivative method. The base composition of these mitochondrial 4 S RNA preparations was compared with the base composition of cytoplasmic and bacterial (Escherichia coli B and Bacillus subtilis) 4-S RNAs. The results of these studies are: 1. When compared with cytoplasmic 4 S RNA, the liver and hepatoma mitochondrial 4-S RNAs are characterized by high (A + U)/(G + C) ratios and low overall degrees of base methylation and modification. 2. The mammalian mitochondrial 4-S RNAs are qualitatively even more different from the bacterial 4-S RNAs than from their cytoplasmic counterparts. Thus, several modified constituents found in both cytoplasmic and mitochondrial 4 S RNA are absent from the bacterial 4-S RNAs. 3. Mitochondrial 4S RNA from both hepatomas was found to be under-methylated and undermodified when compared with normal liver mitochondrial 4S RNA. This trend is more pronounced for the rapidly growing hepatoma 7777 (i.e., 17% undermethylation) than for the more slowly growing hepatoma 5123D (i.e., 8% undermethylation). These findings are discussed in relationship to (1) results of other authors on composition of mitochondrial 4 S RNA, (2) special features of structure and biosynthesis of mitochondrial 4 S RNA, (3) the possible evolutionary origin of mitochondria and (4) the possible role played by aberrant mitochondrial 4 S RNA in altered mitochondrial protein synthesis in tumors.", "contents": "Base composition studies on mitochondrial 4 S RNA from rat liver and Morris hepatomas 5123D and 7777. The major and modified base composition of mitochondrial 4 S RNA from rat liver and from Morris hepatomas 5123D and 7777 has been determined for 16 constituents using a chemical tritium-derivative method. The base composition of these mitochondrial 4 S RNA preparations was compared with the base composition of cytoplasmic and bacterial (Escherichia coli B and Bacillus subtilis) 4-S RNAs. The results of these studies are: 1. When compared with cytoplasmic 4 S RNA, the liver and hepatoma mitochondrial 4-S RNAs are characterized by high (A + U)/(G + C) ratios and low overall degrees of base methylation and modification. 2. The mammalian mitochondrial 4-S RNAs are qualitatively even more different from the bacterial 4-S RNAs than from their cytoplasmic counterparts. Thus, several modified constituents found in both cytoplasmic and mitochondrial 4 S RNA are absent from the bacterial 4-S RNAs. 3. Mitochondrial 4S RNA from both hepatomas was found to be under-methylated and undermodified when compared with normal liver mitochondrial 4S RNA. This trend is more pronounced for the rapidly growing hepatoma 7777 (i.e., 17% undermethylation) than for the more slowly growing hepatoma 5123D (i.e., 8% undermethylation). These findings are discussed in relationship to (1) results of other authors on composition of mitochondrial 4 S RNA, (2) special features of structure and biosynthesis of mitochondrial 4 S RNA, (3) the possible evolutionary origin of mitochondria and (4) the possible role played by aberrant mitochondrial 4 S RNA in altered mitochondrial protein synthesis in tumors."} {"id": "PMID:174750", "title": "Electron spin resonance analysis of irreversible changes induced by calcium perturbation of erythrocyte membranes.", "content": "Introduction of calcium during hemolysis of erythrocytes causes irreversible membrane changes, including protein aggregation. These changes have been investigated by incorporation of one protein and three fatty acid spin label probes into washed membranes from erythrocytes hemolyzed with a range of Ca2+ concentrations. Electron spin resonance spectra of the lipid probes were analyzed for changes in the order parameters, isotropic coupling constants and mean angular deviations of the lipid hydrocarbon chains. The results generally indicated an increased freedom of mobility of the probes with increased Ca2+ concentration during hemolysis, but the response of each probe showed a different concentration dependence. The maximal response was obtained with the I(5, 10) probe. Variations in the responses were interpreted to reflect different modes of protein-lipid or protein-probe interactions arising from Ca2+ -induced membrane protein alterations. Spectra from membranes treated with the protein spin label showed an increased ratio of immobilized to mobile label with increased Ca2+ concentrations at hemolysis. This is consistent with the membrane protein aggregation phenomena previously observed. It is suggested that the increased protein-protein interactions formed as a result of calcium treatment permit an increased lipid mobility in the membrane regions monitored by the fatty acid probes.", "contents": "Electron spin resonance analysis of irreversible changes induced by calcium perturbation of erythrocyte membranes. Introduction of calcium during hemolysis of erythrocytes causes irreversible membrane changes, including protein aggregation. These changes have been investigated by incorporation of one protein and three fatty acid spin label probes into washed membranes from erythrocytes hemolyzed with a range of Ca2+ concentrations. Electron spin resonance spectra of the lipid probes were analyzed for changes in the order parameters, isotropic coupling constants and mean angular deviations of the lipid hydrocarbon chains. The results generally indicated an increased freedom of mobility of the probes with increased Ca2+ concentration during hemolysis, but the response of each probe showed a different concentration dependence. The maximal response was obtained with the I(5, 10) probe. Variations in the responses were interpreted to reflect different modes of protein-lipid or protein-probe interactions arising from Ca2+ -induced membrane protein alterations. Spectra from membranes treated with the protein spin label showed an increased ratio of immobilized to mobile label with increased Ca2+ concentrations at hemolysis. This is consistent with the membrane protein aggregation phenomena previously observed. It is suggested that the increased protein-protein interactions formed as a result of calcium treatment permit an increased lipid mobility in the membrane regions monitored by the fatty acid probes."} {"id": "PMID:174751", "title": "Change in zeta potential and membrane potential of slime mold Physarum polycephalum in response to chemical stimuli.", "content": "Electrophoretic study of microplasmodia of the true slime mold Physarum polycephalum was carried out in the presence of various concentrations of inorganic salts, nucleotides and sugars, and the zeta potential at the surface of the plasmodia was determined from the electrophoretic mobilities. The membrane potential of the plasmodia was also measured under the same external conditions. It was shown that changes in the membrane potential induced by the chemical stimuli agreed approximately with those induced in the zeta potential in all cases examined. These results suggested that the phase boundary potential at the membrane-solution interface is mainly responsible for the membrane potential in the chemoreception of the slime mold.", "contents": "Change in zeta potential and membrane potential of slime mold Physarum polycephalum in response to chemical stimuli. Electrophoretic study of microplasmodia of the true slime mold Physarum polycephalum was carried out in the presence of various concentrations of inorganic salts, nucleotides and sugars, and the zeta potential at the surface of the plasmodia was determined from the electrophoretic mobilities. The membrane potential of the plasmodia was also measured under the same external conditions. It was shown that changes in the membrane potential induced by the chemical stimuli agreed approximately with those induced in the zeta potential in all cases examined. These results suggested that the phase boundary potential at the membrane-solution interface is mainly responsible for the membrane potential in the chemoreception of the slime mold."} {"id": "PMID:174754", "title": "[Role of phospholipids in the generation of membrane potentials by proteoliposomes].", "content": "Closed protein-phospholipid particles (proteoliposomes), obtained by self-assembly method, are capable to generate and to maintain the membrane potential in the case if their protein complex is represented by: a) a complex of mitochondrial ATPase; b) a complex of cytochrome oxidase and cytochrome c and c) bacteriorhodopsin from Halobacterium halobium; and their phospholipid component is represented by phosphatidylethanolamine or by a mixture of mitochondrial phospholipids. Only cytochromoxidase and bacteriorhodopsin (but not ATPase) proteoliposomes with phosphatidylserine are active. Cardiolipin also is not active in experiments with ATPase. Phosphatidylcholine produces in all the cases proteoliposomes incapable of maintaining the membrane potential. It is concluded that the inefficiency of phosphatidylcholine in the formation of proteoliposomes, generating the membrane potential, is due to the impossibility of obtaining closed membrane forms with a high electric resistance. The inefficiency of phosphatidylserine and cardiolipine, in the case of ATPase protein component of proteoliposomes, may be due to a specific requirement of this generator of the membrane potential in phosphatidylethanolamine.", "contents": "[Role of phospholipids in the generation of membrane potentials by proteoliposomes]. Closed protein-phospholipid particles (proteoliposomes), obtained by self-assembly method, are capable to generate and to maintain the membrane potential in the case if their protein complex is represented by: a) a complex of mitochondrial ATPase; b) a complex of cytochrome oxidase and cytochrome c and c) bacteriorhodopsin from Halobacterium halobium; and their phospholipid component is represented by phosphatidylethanolamine or by a mixture of mitochondrial phospholipids. Only cytochromoxidase and bacteriorhodopsin (but not ATPase) proteoliposomes with phosphatidylserine are active. Cardiolipin also is not active in experiments with ATPase. Phosphatidylcholine produces in all the cases proteoliposomes incapable of maintaining the membrane potential. It is concluded that the inefficiency of phosphatidylcholine in the formation of proteoliposomes, generating the membrane potential, is due to the impossibility of obtaining closed membrane forms with a high electric resistance. The inefficiency of phosphatidylserine and cardiolipine, in the case of ATPase protein component of proteoliposomes, may be due to a specific requirement of this generator of the membrane potential in phosphatidylethanolamine."} {"id": "PMID:174755", "title": "[Inositol-containing phospholipids in rat brain and liver].", "content": "A simple modification of the method of Rossiter and Palmer for the quantitative determination of phosphoinositides (PI) in animal tissues (brain and liver) is worked out: Phospholipids are mineralyzed (together with a paper) in 57% perchloric acid, avoiding the time consuming procedure of the tenfold elution of inositids spots from chromatogramms and the subsequent evaporation of the substantial volume of the eluate obtained. The time of the analysis is twice as short as that of the original method, the data obtained being reliable. The quantity of mono-, di- and triphosphoinositides in rat brain is as follows: 85.08, 11.33 and 32.85 mkg P/g wet tissue, but in liver it is 94.5, 1.88 and 2.5 mkg P/g wet tissue respectively.", "contents": "[Inositol-containing phospholipids in rat brain and liver]. A simple modification of the method of Rossiter and Palmer for the quantitative determination of phosphoinositides (PI) in animal tissues (brain and liver) is worked out: Phospholipids are mineralyzed (together with a paper) in 57% perchloric acid, avoiding the time consuming procedure of the tenfold elution of inositids spots from chromatogramms and the subsequent evaporation of the substantial volume of the eluate obtained. The time of the analysis is twice as short as that of the original method, the data obtained being reliable. The quantity of mono-, di- and triphosphoinositides in rat brain is as follows: 85.08, 11.33 and 32.85 mkg P/g wet tissue, but in liver it is 94.5, 1.88 and 2.5 mkg P/g wet tissue respectively."} {"id": "PMID:174756", "title": "[Characteristics of testosterone-binding cytoplasmic components in the human endometrium and their interaction with chromatin].", "content": "The existence of macromolecules which specifically bind 3H-testosterone is demonstrated in the soluble fraction of human uterus endometrium. Testosterone receptors of endometrial cytosol are heterogenous and comprise the component with high affinity (Kd--2,9x10(-10) M) and low capacity (concentration of binding sites--0,5 pmoles per mg of protein) and the component with lower affinity and higher capacity (4x10(-9) M and 4 pmoles/mg of protein respectively). Incubation of sliced of endometrium at 37 (but not at 0 degrees) with 3H-testosterone results in the binding of the steroid by chromatin. On the other hand, testosterone-cytoplasmic receptor complex is able to associate with chromatin at 0 degrees. Chromatin did not bind free 3H-testosterone under these conditions. The existence of the receptor for testosterone in endometrial cells promoting its transport into the nucleus and binding with chromatin corroborates the previously shown specific action of testosterone on messenger RNA biogenesis in the uterus. Polyinductor model of regulation of gene expression in higher organisms by steroid hormones is discussed.", "contents": "[Characteristics of testosterone-binding cytoplasmic components in the human endometrium and their interaction with chromatin]. The existence of macromolecules which specifically bind 3H-testosterone is demonstrated in the soluble fraction of human uterus endometrium. Testosterone receptors of endometrial cytosol are heterogenous and comprise the component with high affinity (Kd--2,9x10(-10) M) and low capacity (concentration of binding sites--0,5 pmoles per mg of protein) and the component with lower affinity and higher capacity (4x10(-9) M and 4 pmoles/mg of protein respectively). Incubation of sliced of endometrium at 37 (but not at 0 degrees) with 3H-testosterone results in the binding of the steroid by chromatin. On the other hand, testosterone-cytoplasmic receptor complex is able to associate with chromatin at 0 degrees. Chromatin did not bind free 3H-testosterone under these conditions. The existence of the receptor for testosterone in endometrial cells promoting its transport into the nucleus and binding with chromatin corroborates the previously shown specific action of testosterone on messenger RNA biogenesis in the uterus. Polyinductor model of regulation of gene expression in higher organisms by steroid hormones is discussed."} {"id": "PMID:174762", "title": "Cyclic AMP in developing muscle of the rhesus monkey: effect of prostaglandin E.", "content": "Cyclic AMP levels, measured by a competitive protein-binding assay and by a prelabeling technique with adenine-14 C, were determined on fetal, infant, and adult heart, diaphragm, and skeletal muscle of the rhesus monkey (Macaca mulatta); the effect of PGE on cyclic AMP accumulation was also studied. The levels of cyclic AMP were higher in the 3 types of muscle from 150-day fetuses (91% of term) than in adult muscles and even higher at 78-100 days fetal age, and histological evidence indicated that by 65 days gestation, the majority of the rhesus skeletal muscle cells are in the myotube stage. These data agree with the observation in cell cultures that a decrease in cyclic AMP is correlated with fusion of myoblasts to form myotubes. PGE (2.8 MUM) stimulated cyclic AMP accumulation in all the fetal series, even in the earliest series (47% of term), as well as in all the adult series.", "contents": "Cyclic AMP in developing muscle of the rhesus monkey: effect of prostaglandin E. Cyclic AMP levels, measured by a competitive protein-binding assay and by a prelabeling technique with adenine-14 C, were determined on fetal, infant, and adult heart, diaphragm, and skeletal muscle of the rhesus monkey (Macaca mulatta); the effect of PGE on cyclic AMP accumulation was also studied. The levels of cyclic AMP were higher in the 3 types of muscle from 150-day fetuses (91% of term) than in adult muscles and even higher at 78-100 days fetal age, and histological evidence indicated that by 65 days gestation, the majority of the rhesus skeletal muscle cells are in the myotube stage. These data agree with the observation in cell cultures that a decrease in cyclic AMP is correlated with fusion of myoblasts to form myotubes. PGE (2.8 MUM) stimulated cyclic AMP accumulation in all the fetal series, even in the earliest series (47% of term), as well as in all the adult series."} {"id": "PMID:174758", "title": "[The relationship between cholesterol, shpingomyelin and phosphatidyl choline in liver and hepatoma cell membranes].", "content": "The cholesterol, sphingomyelin and phosphatidylcholine content in different cell membranes of liver and hepatoma was studied. Significant amounts of cholesterol were found in all the subcellular fractions of hepatoma, whereas in the liver cholesterol is localized mainly in the plasma membranes. A direct relation between the content of cholesterol and sphingomyelin was demonstrated. Possible effects of the cholesterol : : sphingomyelin : phosphatidylcholine ratio on the properties of cell membranes are discussed.", "contents": "[The relationship between cholesterol, shpingomyelin and phosphatidyl choline in liver and hepatoma cell membranes]. The cholesterol, sphingomyelin and phosphatidylcholine content in different cell membranes of liver and hepatoma was studied. Significant amounts of cholesterol were found in all the subcellular fractions of hepatoma, whereas in the liver cholesterol is localized mainly in the plasma membranes. A direct relation between the content of cholesterol and sphingomyelin was demonstrated. Possible effects of the cholesterol : : sphingomyelin : phosphatidylcholine ratio on the properties of cell membranes are discussed."} {"id": "PMID:174757", "title": "[Control of glutamate dehydrogenase activity in isolated rat liver mitochondria by purine nucleotides, cyclic AMP, alpha-ketoglutarate and phosphate].", "content": "Glutamate oxidation by mitochondria in the presence of arsenite and dinitrophenol is diminished by ADP, AMP, GDP and cyclic 3',5'-AMP. Mechanism of inhibition is noncompetitive and atractyloside-sensitive. Alpha-ketoglutarate is a more powerful inhibitor of glutamate oxidation. Inhibitions produced by alpha-ketoglutarate and nucleotide are not additive. Phosphate reverses inhibition of glutamate oxidation produced by nucleotides but only slightly that produced by alpha-ketoglutarate. It is concluded from the results obtained that GDH remains in intact mitochondria under effective control exerted by purine nucleotides (AMP, GDP, ADP, cAMP), alpha-ketoglutarate and phosphate, functioning mainly in the direction of reductive amination of alpha-ketoglutarate.", "contents": "[Control of glutamate dehydrogenase activity in isolated rat liver mitochondria by purine nucleotides, cyclic AMP, alpha-ketoglutarate and phosphate]. Glutamate oxidation by mitochondria in the presence of arsenite and dinitrophenol is diminished by ADP, AMP, GDP and cyclic 3',5'-AMP. Mechanism of inhibition is noncompetitive and atractyloside-sensitive. Alpha-ketoglutarate is a more powerful inhibitor of glutamate oxidation. Inhibitions produced by alpha-ketoglutarate and nucleotide are not additive. Phosphate reverses inhibition of glutamate oxidation produced by nucleotides but only slightly that produced by alpha-ketoglutarate. It is concluded from the results obtained that GDH remains in intact mitochondria under effective control exerted by purine nucleotides (AMP, GDP, ADP, cAMP), alpha-ketoglutarate and phosphate, functioning mainly in the direction of reductive amination of alpha-ketoglutarate."} {"id": "PMID:174763", "title": "[The synchronizing effect of cyclic 3',5'-adenosine monophosphate on the mitotic cycle of Ehrlich ascitic carcinoma cells].", "content": "A study was made of the number of mitoses and of the DNA-synthesizing cells in the ascitic Ehrlich carcinoma in the course of 24 hours after the injection of cyclic 3',5'-adenosinmonophosphate to mice. It was found that as the result of the preprrophase inhibition and, possibly, of stimulation of the cell entry into the S-phase, 8 hours after the action a great number of cells began to divide almost simultaneously. The effect of mitosis synchronization was assessed in the tumour cell population.", "contents": "[The synchronizing effect of cyclic 3',5'-adenosine monophosphate on the mitotic cycle of Ehrlich ascitic carcinoma cells]. A study was made of the number of mitoses and of the DNA-synthesizing cells in the ascitic Ehrlich carcinoma in the course of 24 hours after the injection of cyclic 3',5'-adenosinmonophosphate to mice. It was found that as the result of the preprrophase inhibition and, possibly, of stimulation of the cell entry into the S-phase, 8 hours after the action a great number of cells began to divide almost simultaneously. The effect of mitosis synchronization was assessed in the tumour cell population."} {"id": "PMID:174764", "title": "[Nuclear estradiol receptors in several \"non-target\" organs of rats].", "content": "Some properties of the macromolecules of the KCl-extracts of the nuclei of the uterus, kidney, liver, testis and prostate, specifically binding estradiol (E2), were studied. These macromolecules of the uterus and the liver were found to be maximally extracted from chromatin by the 0.6 M KCl concentration. The capacity of the macromolecules of the uterine, kidney and liver nuclear extracts to bind E2 specifically is destroyed completely by pronase, but not by RNA-ASe and DNA-ase, pointing to the protein nature of these macromolecules. Only estrogenic compounds, but not testosterone, 5alpha-dihydrotestosterone, progesterone or corticosterone were capable to compete with H3--E2 for the E2--binding sites of the macromolecules of the nuclear extracts of all the organs investigaeted. It is assumed that macromolecules of the nuclei of the investigated nontarget organs specifically binding E2 are estrogen receptors.", "contents": "[Nuclear estradiol receptors in several \"non-target\" organs of rats]. Some properties of the macromolecules of the KCl-extracts of the nuclei of the uterus, kidney, liver, testis and prostate, specifically binding estradiol (E2), were studied. These macromolecules of the uterus and the liver were found to be maximally extracted from chromatin by the 0.6 M KCl concentration. The capacity of the macromolecules of the uterine, kidney and liver nuclear extracts to bind E2 specifically is destroyed completely by pronase, but not by RNA-ASe and DNA-ase, pointing to the protein nature of these macromolecules. Only estrogenic compounds, but not testosterone, 5alpha-dihydrotestosterone, progesterone or corticosterone were capable to compete with H3--E2 for the E2--binding sites of the macromolecules of the nuclear extracts of all the organs investigaeted. It is assumed that macromolecules of the nuclei of the investigated nontarget organs specifically binding E2 are estrogen receptors."} {"id": "PMID:174765", "title": "Occurrence and function of cyclic nucleotides in blood vessels.", "content": "The literature concerned with studies of the occurrence and function of the cyclic nucleotides in blood vessels is reviewed. Emphasis is placed on the critical evaluation of the evidence which relates to the hypothesis that cyclic nucleotides meditate the effects of drugs and neurotransmitters on vascular contractility. The hypothesis that cyclic AMP mediates vasodilation, especially that induced by beta-adrenergic relaxation, is supported by many experimental approaches, but it is concluded that the evidence remains unconvincing based on the criteria established for such a mediator role. Possible sites of action of cyclic AMP are discussed. The demonstrated action of cyclic AMP on vascular membrane electrophysiology and calcium ion pumps are reviewed as possible causes of relaxation. The role of both nucleotides in vascular disease, especially hypertension is discussed. Finally the needs for further research in this area are suggested.", "contents": "Occurrence and function of cyclic nucleotides in blood vessels. The literature concerned with studies of the occurrence and function of the cyclic nucleotides in blood vessels is reviewed. Emphasis is placed on the critical evaluation of the evidence which relates to the hypothesis that cyclic nucleotides meditate the effects of drugs and neurotransmitters on vascular contractility. The hypothesis that cyclic AMP mediates vasodilation, especially that induced by beta-adrenergic relaxation, is supported by many experimental approaches, but it is concluded that the evidence remains unconvincing based on the criteria established for such a mediator role. Possible sites of action of cyclic AMP are discussed. The demonstrated action of cyclic AMP on vascular membrane electrophysiology and calcium ion pumps are reviewed as possible causes of relaxation. The role of both nucleotides in vascular disease, especially hypertension is discussed. Finally the needs for further research in this area are suggested."} {"id": "PMID:174768", "title": "The effects of lithium ions on the antidiuretic action of vasopressin in the rat.", "content": "1 The effect of intravenous infusion of lithium, 2.56 mumol/min on the antidiuretic responses to antidiuretic hormone (ADH), adenosine triphosphate (ATP), 3'-5' adenosine cylic monophosphate (cyclic AMP) and theophyline was studied in water-loaded, alcohol-anaesthetized rats. 2 Lithium reversibly inhibits the antidiuretic response to all concentrations of ADH, depressing the maximum response but not changing the amount required for half maximal response. 3 The rate of increase of serum lithium relates more clearly to the inhibitory effect than does the serum concentration. 4 Sodium concentrations in the renal papilla seem to fall when serum lithium levels are rising. 5 Lithium inhibits the antidiuretic response to ATP and cyclic AMP but does not inhibit the response to theophyline.", "contents": "The effects of lithium ions on the antidiuretic action of vasopressin in the rat. 1 The effect of intravenous infusion of lithium, 2.56 mumol/min on the antidiuretic responses to antidiuretic hormone (ADH), adenosine triphosphate (ATP), 3'-5' adenosine cylic monophosphate (cyclic AMP) and theophyline was studied in water-loaded, alcohol-anaesthetized rats. 2 Lithium reversibly inhibits the antidiuretic response to all concentrations of ADH, depressing the maximum response but not changing the amount required for half maximal response. 3 The rate of increase of serum lithium relates more clearly to the inhibitory effect than does the serum concentration. 4 Sodium concentrations in the renal papilla seem to fall when serum lithium levels are rising. 5 Lithium inhibits the antidiuretic response to ATP and cyclic AMP but does not inhibit the response to theophyline."} {"id": "PMID:174766", "title": "[Cytology of various rare benign tumors of the breast].", "content": "The authors describe the cytological appearances of three rare benign mammary tumors (granular cell myoblastoma, sebaceous cyst and fibrous histiocytoma), and warn the clinician against over-optimism when presented with a benign cytologic diagnosis. In fact, the proportion of cases in which carcinoma is confused with a benign tumour varies from 3 to 5% according to statistics. They analyse the various causes responsible for the \"false benign\" diagnosis. The author's opinion is that one can only arrive at the cytological diagnosis of benignity as part of a group of investigations. Final diagnosis must depend upon a histological examination.", "contents": "[Cytology of various rare benign tumors of the breast]. The authors describe the cytological appearances of three rare benign mammary tumors (granular cell myoblastoma, sebaceous cyst and fibrous histiocytoma), and warn the clinician against over-optimism when presented with a benign cytologic diagnosis. In fact, the proportion of cases in which carcinoma is confused with a benign tumour varies from 3 to 5% according to statistics. They analyse the various causes responsible for the \"false benign\" diagnosis. The author's opinion is that one can only arrive at the cytological diagnosis of benignity as part of a group of investigations. Final diagnosis must depend upon a histological examination."} {"id": "PMID:174767", "title": "[Immunologic results obtained with an experimental system oftransplantable colonic tumors. Possible applications of these results to human intestinal tumors].", "content": "Intestinal cancers, morphologically very close to human colo-rectal adeno-carcinoma, have been induced by dimethylhydrazine in inbred rats. Graftable lines have been obtained from 5 primary intestinal tumors, and 3 cell lines have been cultivated from the grafts. This model was used to demonstrate carcinofetal antigen(s) on the surface of the intestinal cancer cells. Circulating antibodies against tumor-associated antigen(s) have been found in tumor-bearing rats. Cancer enhancement was regularly observed when specific (tumor cells) and non-specific (B.C.G.) immunologic treatments were used to prevent or cure rat intestinal tumors. These results suggest that immunotherapy of human colo-rectal cancer might be hazardous.", "contents": "[Immunologic results obtained with an experimental system oftransplantable colonic tumors. Possible applications of these results to human intestinal tumors]. Intestinal cancers, morphologically very close to human colo-rectal adeno-carcinoma, have been induced by dimethylhydrazine in inbred rats. Graftable lines have been obtained from 5 primary intestinal tumors, and 3 cell lines have been cultivated from the grafts. This model was used to demonstrate carcinofetal antigen(s) on the surface of the intestinal cancer cells. Circulating antibodies against tumor-associated antigen(s) have been found in tumor-bearing rats. Cancer enhancement was regularly observed when specific (tumor cells) and non-specific (B.C.G.) immunologic treatments were used to prevent or cure rat intestinal tumors. These results suggest that immunotherapy of human colo-rectal cancer might be hazardous."} {"id": "PMID:174772", "title": "Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function.", "content": "The adrenocortical response to the simple 30-minute ACTH stimulation test was compared with the hypothalamic-pituitary-adrenocortical (HPA) response to insulin-induced hypoglycaemia in 25 patients with various degrees of hypothalamic-pituitary malfunction. The correlations between the increase in plasma cortisol during insulin hypoglycaemia and that during ACTH stimulation (r = 0-66) and between peak plasma cortisol levels during the two tests (r = 0-90) were highly significant. Peak plasma cortisol levels in individual patients were similar on both tests, no patient showing any major discrepancy between the two test results. Thus the simple 30-minute ACTH stimulation test seems to be reliable in detecting imparied HPA function.", "contents": "Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function. The adrenocortical response to the simple 30-minute ACTH stimulation test was compared with the hypothalamic-pituitary-adrenocortical (HPA) response to insulin-induced hypoglycaemia in 25 patients with various degrees of hypothalamic-pituitary malfunction. The correlations between the increase in plasma cortisol during insulin hypoglycaemia and that during ACTH stimulation (r = 0-66) and between peak plasma cortisol levels during the two tests (r = 0-90) were highly significant. Peak plasma cortisol levels in individual patients were similar on both tests, no patient showing any major discrepancy between the two test results. Thus the simple 30-minute ACTH stimulation test seems to be reliable in detecting imparied HPA function."} {"id": "PMID:174774", "title": "Inpatients in an accident unit.", "content": "A one-year prospective study was undertaken in the 79-bed accident unit of the Bristol Royal Infirmary to define reasons for continuing inpatient care. This showed that, of a consecutive series of 466 patients staying in hospital for over two weeks, 35% lengthened their stay beyond that needed for acute nursing or continued medical care. A combination of factors usually led to total social dependence, the major problem being the absence of a caring relative. Other factors included pre-existing locomotor disorder or mental infirmity, unmanageable incontinence of urine after catheterisation, and institutional disorientation. If the pattern of management of elderly patients after injury is not changed and beds are to be kept available for the newly injured the unit will need about 50 new long-stay beds each year.", "contents": "Inpatients in an accident unit. A one-year prospective study was undertaken in the 79-bed accident unit of the Bristol Royal Infirmary to define reasons for continuing inpatient care. This showed that, of a consecutive series of 466 patients staying in hospital for over two weeks, 35% lengthened their stay beyond that needed for acute nursing or continued medical care. A combination of factors usually led to total social dependence, the major problem being the absence of a caring relative. Other factors included pre-existing locomotor disorder or mental infirmity, unmanageable incontinence of urine after catheterisation, and institutional disorientation. If the pattern of management of elderly patients after injury is not changed and beds are to be kept available for the newly injured the unit will need about 50 new long-stay beds each year."} {"id": "PMID:174779", "title": "A two-pathway informon theory of conditioning and adaptive pattern recognition.", "content": "A neural network theory is proposed which offers an explanation of many of the facts of classical and operant conditioning and adaptive pattern recognition. Interconnected networks of units have been studied and simulated which embody only two rules; firstly, units have inputs from pathways of variable and of fixed conductivity; secondly, the conductivity of a variable pathway is made proportional to the negative of the mutual information function between the signals at its input and output. The signal in a fixed pathway indicates whether the total input to the variable pathways is a member or not of some class. After a learning phase in which the unit, called an informon, receives such labelled inputs, it is able to predict the class of future unlabelled inputs. Such units are stable and their steady state can be calculated.", "contents": "A two-pathway informon theory of conditioning and adaptive pattern recognition. A neural network theory is proposed which offers an explanation of many of the facts of classical and operant conditioning and adaptive pattern recognition. Interconnected networks of units have been studied and simulated which embody only two rules; firstly, units have inputs from pathways of variable and of fixed conductivity; secondly, the conductivity of a variable pathway is made proportional to the negative of the mutual information function between the signals at its input and output. The signal in a fixed pathway indicates whether the total input to the variable pathways is a member or not of some class. After a learning phase in which the unit, called an informon, receives such labelled inputs, it is able to predict the class of future unlabelled inputs. Such units are stable and their steady state can be calculated."} {"id": "PMID:174780", "title": "Simulation studies of learning in an informon network.", "content": "A single informon reproduces classical conditioning to compound stimuli under a wide range of conditions during reinforcement and non-reinforcement; it also reproduces simple operant conditioning. A network of 210 informons with 8400 simultaneouslly varying pathways has been simulated; it can learn to recognize handprinted numerals. The networks studied must be more richly interconnected before they can reproduce more detailed behaviour of animals.", "contents": "Simulation studies of learning in an informon network. A single informon reproduces classical conditioning to compound stimuli under a wide range of conditions during reinforcement and non-reinforcement; it also reproduces simple operant conditioning. A network of 210 informons with 8400 simultaneouslly varying pathways has been simulated; it can learn to recognize handprinted numerals. The networks studied must be more richly interconnected before they can reproduce more detailed behaviour of animals."} {"id": "PMID:174781", "title": "Neurophysiological predictions of a two-pathway informon theory of neural conditioning.", "content": "According to the informon theory there must be variable and fixed synapses in a neurone for conditioning to occur. For a variable synapse to behave like an informon pathway its conductivity needs to depend only on the average values of its presynaptic potential and of the internal state of the neurone. Eight predictions are made about the detailed functioning of such a synapse. In a minimal hypothesis all fixed synapses are inhibitory; but sign reversals are considered. Let one unit A in the receptive field of a neurone drive it through a fixed synapse, and all other units, e.g. B, drive variable synapses; then the theory predicts that the conductivity of the B synapse becomes proportional to the mutual information function between the signals at A and B; so inputs which tend to occur with the A signal become connected positively to the neurone. Applied to visual pathways this principle leads to the formation of edge and grating detectors. If X and Y cells excite variable and fixed synapses respectively, simple and complex cells should be driven by both X and Y cells, the latter being inhibitory. The two-pathway theory resolves two apparent conflicts between experimental facts.", "contents": "Neurophysiological predictions of a two-pathway informon theory of neural conditioning. According to the informon theory there must be variable and fixed synapses in a neurone for conditioning to occur. For a variable synapse to behave like an informon pathway its conductivity needs to depend only on the average values of its presynaptic potential and of the internal state of the neurone. Eight predictions are made about the detailed functioning of such a synapse. In a minimal hypothesis all fixed synapses are inhibitory; but sign reversals are considered. Let one unit A in the receptive field of a neurone drive it through a fixed synapse, and all other units, e.g. B, drive variable synapses; then the theory predicts that the conductivity of the B synapse becomes proportional to the mutual information function between the signals at A and B; so inputs which tend to occur with the A signal become connected positively to the neurone. Applied to visual pathways this principle leads to the formation of edge and grating detectors. If X and Y cells excite variable and fixed synapses respectively, simple and complex cells should be driven by both X and Y cells, the latter being inhibitory. The two-pathway theory resolves two apparent conflicts between experimental facts."} {"id": "PMID:174787", "title": "[Ultrastructural study of secondary cultures of rat aorta. Cellular aspects].", "content": "Cells obtained from the media and intima of ten days rat aorta, after enzymatic dissociation, were grown in subculture for up to three months. Electron microscopic observations demonstrate that these cells maintained the morphology of smooth muscle cells at all phases of their growth in subculture and kept their ability to synthesize and secrete intracellular proteins with better enzymatic features than the cells obtained by proliferation at the periphery of an explant.", "contents": "[Ultrastructural study of secondary cultures of rat aorta. Cellular aspects]. Cells obtained from the media and intima of ten days rat aorta, after enzymatic dissociation, were grown in subculture for up to three months. Electron microscopic observations demonstrate that these cells maintained the morphology of smooth muscle cells at all phases of their growth in subculture and kept their ability to synthesize and secrete intracellular proteins with better enzymatic features than the cells obtained by proliferation at the periphery of an explant."} {"id": "PMID:174788", "title": "[Organotype culture of glandular tissue of the testis of Gabius niger L. Association with hypophysis].", "content": "The endocrine gland of the testis of Gobius niger L. was cultured separately for three or six days by dissecting out from the seminal mass. During the sexual resting periode, the explantation don't induce histological changes; however, during the phase of high sexual activity, the explantation involves marked asthenic signs. This phenomenon is in all cases reversed by the association with pituitaries, even after a preliminary isolated culture of three days. The association with pituitaries increases also the functional activity of the explants compared with the controls tested by measuring the total amount of testosterone contained in pooled culture media, or the global metabolism of 14C sodium acetate.", "contents": "[Organotype culture of glandular tissue of the testis of Gabius niger L. Association with hypophysis]. The endocrine gland of the testis of Gobius niger L. was cultured separately for three or six days by dissecting out from the seminal mass. During the sexual resting periode, the explantation don't induce histological changes; however, during the phase of high sexual activity, the explantation involves marked asthenic signs. This phenomenon is in all cases reversed by the association with pituitaries, even after a preliminary isolated culture of three days. The association with pituitaries increases also the functional activity of the explants compared with the controls tested by measuring the total amount of testosterone contained in pooled culture media, or the global metabolism of 14C sodium acetate."} {"id": "PMID:174789", "title": "[Enzyme alterations of the arterial wall following the combination of a lathyrogenic treatment and of moderate hypercholesterolemia in the young rabbit].", "content": "To determinate the part of humoural and parietal factors in atherosclerotic injury genesis, metabolism alteration study is realised on aortic cell wall of rabbits which are submitted to a chronical lathyritic intoxication alone, or simultaneously or alternatively associated with a cholesterolemic diet. Catabolic activity increase of beta-glucuronidase occurs in hypercholesterolemic rabbits. Beta-aminoproprionitrile, lathyrogenic drug used, stimulates biosynthetic pathways: increase of soluble proteins, energetic enzyme activities (lacticodeshydrogenase, malicodeshydrogenase), conjonctival protein metabolism (procollagen lysyl hydroxylase); in the same time, cell wall disturbances and lipidic deposits are facilitate when rabbits are submitted to cholesterolemic diet.", "contents": "[Enzyme alterations of the arterial wall following the combination of a lathyrogenic treatment and of moderate hypercholesterolemia in the young rabbit]. To determinate the part of humoural and parietal factors in atherosclerotic injury genesis, metabolism alteration study is realised on aortic cell wall of rabbits which are submitted to a chronical lathyritic intoxication alone, or simultaneously or alternatively associated with a cholesterolemic diet. Catabolic activity increase of beta-glucuronidase occurs in hypercholesterolemic rabbits. Beta-aminoproprionitrile, lathyrogenic drug used, stimulates biosynthetic pathways: increase of soluble proteins, energetic enzyme activities (lacticodeshydrogenase, malicodeshydrogenase), conjonctival protein metabolism (procollagen lysyl hydroxylase); in the same time, cell wall disturbances and lipidic deposits are facilitate when rabbits are submitted to cholesterolemic diet."} {"id": "PMID:174790", "title": "[Concentration of viruses in water by the 2 phase polymer method: quantitative study].", "content": "The authors attempt to determine the sensibility of polymer two phases system applied to the concentration of viruses from water. They show that this technic agrees to the research of poliomyelitic viruses in waters since viral recuperation is always upper than 74.5%. Besides, they notice that average percentages of regained viruses are always 100% where the initial concentrations of viruses are 10(2) or 10(3) per liter; on the other hand if the initial concentration is higher the yield of this method is decreasing.", "contents": "[Concentration of viruses in water by the 2 phase polymer method: quantitative study]. The authors attempt to determine the sensibility of polymer two phases system applied to the concentration of viruses from water. They show that this technic agrees to the research of poliomyelitic viruses in waters since viral recuperation is always upper than 74.5%. Besides, they notice that average percentages of regained viruses are always 100% where the initial concentrations of viruses are 10(2) or 10(3) per liter; on the other hand if the initial concentration is higher the yield of this method is decreasing."} {"id": "PMID:174791", "title": "[Existence of cytoplasmic inclusions in acinic cells of the exocrine pancreas of the hyperglycemic obese mouse].", "content": "Peculiar cytoplasmic inclusions with crystalline pattern are described in the obese hyperglycaemic mouse pancreas acinar cells. They are generally associated with filamentous structures. However, crystalline and filamentous inclusions have also been observed in isolated forms. These inclusions are not digested by pronase. Since they have also been encountered in normal mice, it seems that the hyperglycaemic syndrome does not play a role in inducing their formation.", "contents": "[Existence of cytoplasmic inclusions in acinic cells of the exocrine pancreas of the hyperglycemic obese mouse]. Peculiar cytoplasmic inclusions with crystalline pattern are described in the obese hyperglycaemic mouse pancreas acinar cells. They are generally associated with filamentous structures. However, crystalline and filamentous inclusions have also been observed in isolated forms. These inclusions are not digested by pronase. Since they have also been encountered in normal mice, it seems that the hyperglycaemic syndrome does not play a role in inducing their formation."} {"id": "PMID:174792", "title": "[Intracellular processes leading to the induction of insulin membrane receptors. Study on Acetabularia mediterranea].", "content": "Algal cells have been incubated for 7 to 10 days in darkness in sea water containing either actinomycin D or cycloheximide (10 mug/ml) or fructose glucose (5.5 mM). Measurements of insulin fixation to whole cells, plasma membranes or cytosol fractions after that treatment indicate that dark consumption of chloroplastic fructosans stored in photosynthetic conditions would lead to a \"signal\" inducing translation and transcription of nuclear DNA genetic message resulting in an increase of the number of insulin cellular receptor sites.", "contents": "[Intracellular processes leading to the induction of insulin membrane receptors. Study on Acetabularia mediterranea]. Algal cells have been incubated for 7 to 10 days in darkness in sea water containing either actinomycin D or cycloheximide (10 mug/ml) or fructose glucose (5.5 mM). Measurements of insulin fixation to whole cells, plasma membranes or cytosol fractions after that treatment indicate that dark consumption of chloroplastic fructosans stored in photosynthetic conditions would lead to a \"signal\" inducing translation and transcription of nuclear DNA genetic message resulting in an increase of the number of insulin cellular receptor sites."} {"id": "PMID:174793", "title": "[Mesentery capillary barrier in rats injected intravascularly with ascitic Zajdela hepatoma. III. Effect of serotonin and histamine on the extravasation of the tumor].", "content": "The addition of serotonin or of histamin with tumoral cells of ascitic Zajdela's hepatoma and their injection in aorta induce plain hemodynamic changes and increase the tumoral extravasation. So only cells blocked in thrombi are observed in blood vessels. Therefore, serotonin and histamin do facilitate tumoral cells extravasation, allowing so a better metastatic diffusion in this experimental pattern.", "contents": "[Mesentery capillary barrier in rats injected intravascularly with ascitic Zajdela hepatoma. III. Effect of serotonin and histamine on the extravasation of the tumor]. The addition of serotonin or of histamin with tumoral cells of ascitic Zajdela's hepatoma and their injection in aorta induce plain hemodynamic changes and increase the tumoral extravasation. So only cells blocked in thrombi are observed in blood vessels. Therefore, serotonin and histamin do facilitate tumoral cells extravasation, allowing so a better metastatic diffusion in this experimental pattern."} {"id": "PMID:174794", "title": "Transplantable colon tumors as chemotherapy screening models.", "content": "A series of transplantable murine colon tumors have been developed from primary tumors induced by dimethylhydrazine. They are moderately- to well-differentiated adenocarcinomas which retain their histologic appearance and growth characteristics through successive transplant generations. The sensitivity of two tumor lines to 11 standard drugs is reported and some correlation shown with the sensitivity of human colorectal tumors to the same drugs. Therapeutic indices are low and each tumor has an individual pattern of sensitivity. The models have potential as secondary drug screening systems and for investigation of factors affecting drug sensitivity.", "contents": "Transplantable colon tumors as chemotherapy screening models. A series of transplantable murine colon tumors have been developed from primary tumors induced by dimethylhydrazine. They are moderately- to well-differentiated adenocarcinomas which retain their histologic appearance and growth characteristics through successive transplant generations. The sensitivity of two tumor lines to 11 standard drugs is reported and some correlation shown with the sensitivity of human colorectal tumors to the same drugs. Therapeutic indices are low and each tumor has an individual pattern of sensitivity. The models have potential as secondary drug screening systems and for investigation of factors affecting drug sensitivity."} {"id": "PMID:174795", "title": "The chemistry of carcinoembryonic antigen.", "content": "The structure of carcinoembryonic antigen is being determined as an approach to greater diagnostic specificity in the radioimmune assay. Examination by combined gas chromatography-mass spectrometry of derivatized saccharides from CEA has given a general outline of its carbohydrate structure. Sialic acid and fucose were completely destroyed, and galactose and mannose were partially destroyed by a single periodate treatment. Serial periodate oxidation (Smith degradation) destroyed additional amounts of galactose and mannose, as well as significant amounts of N-acetylglucosamine. Antigenic activity persisted, indicating that the residues destroyed played little, if any, part in the antigenicity of DEA.", "contents": "The chemistry of carcinoembryonic antigen. The structure of carcinoembryonic antigen is being determined as an approach to greater diagnostic specificity in the radioimmune assay. Examination by combined gas chromatography-mass spectrometry of derivatized saccharides from CEA has given a general outline of its carbohydrate structure. Sialic acid and fucose were completely destroyed, and galactose and mannose were partially destroyed by a single periodate treatment. Serial periodate oxidation (Smith degradation) destroyed additional amounts of galactose and mannose, as well as significant amounts of N-acetylglucosamine. Antigenic activity persisted, indicating that the residues destroyed played little, if any, part in the antigenicity of DEA."} {"id": "PMID:174796", "title": "Correlation of tumor burden with in vitro lymphocyte reactivity and antibodies to herpesvirus tumor-associated antigens in head and neck squamous carcinoma.", "content": "In 94 patients with squamous carcinoma of the head and neck region, the clinical extent of tumor was correlated with in vitro lymphocyte reactivity (LR) to phytohemagglutinin (PHA) and serum complement-fixing antibodies to herpes simplex virus (HSV)-induced tumor-associated antigen (TAA). Forty-six patients were tumor-bearing and 48 were considered cured. Controls were 41 age-matched normals with histories of similar cigarette consumption. In 15 patients with Stage I carcinomas of the larynx, among whom the tumor diameter was 5 mm or less, mean LR or PHA did not differ from controls and 7 of 11 tested (63%) had antibodies to HSV-TAA. In 83 patients with more extensive tumors, LR to PHA was significantly lower than controls and 42 of 44 tested (95%) had antibodies to HSV-TAA. In both groups, LR to PHA was similar among tumor-bearing and cured patients. The study delineates a clinical tumor burden associated with impaired LR to PHA and a high incidence of antibodies to HSV-TAA in patients with squamous carcinomas of the head and neck region, and shows a correlation between the immune defects in clinically cured patients and tumor extent prior to treatment.", "contents": "Correlation of tumor burden with in vitro lymphocyte reactivity and antibodies to herpesvirus tumor-associated antigens in head and neck squamous carcinoma. In 94 patients with squamous carcinoma of the head and neck region, the clinical extent of tumor was correlated with in vitro lymphocyte reactivity (LR) to phytohemagglutinin (PHA) and serum complement-fixing antibodies to herpes simplex virus (HSV)-induced tumor-associated antigen (TAA). Forty-six patients were tumor-bearing and 48 were considered cured. Controls were 41 age-matched normals with histories of similar cigarette consumption. In 15 patients with Stage I carcinomas of the larynx, among whom the tumor diameter was 5 mm or less, mean LR or PHA did not differ from controls and 7 of 11 tested (63%) had antibodies to HSV-TAA. In 83 patients with more extensive tumors, LR to PHA was significantly lower than controls and 42 of 44 tested (95%) had antibodies to HSV-TAA. In both groups, LR to PHA was similar among tumor-bearing and cured patients. The study delineates a clinical tumor burden associated with impaired LR to PHA and a high incidence of antibodies to HSV-TAA in patients with squamous carcinomas of the head and neck region, and shows a correlation between the immune defects in clinically cured patients and tumor extent prior to treatment."} {"id": "PMID:174797", "title": "Cytoplasmic tubular arrays in cells of American Burkitt's type lymphoma.", "content": "Aggregates of tubular arrays associated with cysternae of endoplasmic reticulum were observed in untreated primary American form Burkitt's lymphoma. The tumor occurred in a white female child who died with severe central nervous system (CNS) involvement. Although the significance of the tubular structures and the mechanism by which they are formed remains unknown, the predilection of these structures for lymphoid and reticuloendothelial cells and their frequent association with either viral or suspected viral conditions cannot be overlooked. However, it is possible that the tubular structures may reflect an increased production of antibody protein in response to a viral antigen.", "contents": "Cytoplasmic tubular arrays in cells of American Burkitt's type lymphoma. Aggregates of tubular arrays associated with cysternae of endoplasmic reticulum were observed in untreated primary American form Burkitt's lymphoma. The tumor occurred in a white female child who died with severe central nervous system (CNS) involvement. Although the significance of the tubular structures and the mechanism by which they are formed remains unknown, the predilection of these structures for lymphoid and reticuloendothelial cells and their frequent association with either viral or suspected viral conditions cannot be overlooked. However, it is possible that the tubular structures may reflect an increased production of antibody protein in response to a viral antigen."} {"id": "PMID:174798", "title": "Ultrastructure of elastosis in scirrhous carcinoma of the breast.", "content": "The stroma of scirrhous breast carcinoma frequently contains an abundance of material with the histologic staining properties of elastic tissue referred to as elastosis. In the present study, this lesion was found to correspond at the ultrastructural level to elastic fibers of various sizes and random orientation. These fibers displayed the two characteristic components, consisting of an amorphous core with a peripheral mantle of microfibrils. Interspersed among the elastic fibers were modified fibroblasts. These cells exhibited an irregular contour with numerous cytoplasmic processes and indentations. Their cytoplasm contained abundant rough endoplasmic reticulum, prominent Golgi complexes, and bundles of filaments. In the extracellular space, elastic fibers were often closely apposed to the plasma membrane of the fibroblasts. Carcinoma cells were also observed in the elastic tissue. It is postulated that fibroblasts, probably under an inductive influence from cancer cells, are the cells responsible for elastic production.", "contents": "Ultrastructure of elastosis in scirrhous carcinoma of the breast. The stroma of scirrhous breast carcinoma frequently contains an abundance of material with the histologic staining properties of elastic tissue referred to as elastosis. In the present study, this lesion was found to correspond at the ultrastructural level to elastic fibers of various sizes and random orientation. These fibers displayed the two characteristic components, consisting of an amorphous core with a peripheral mantle of microfibrils. Interspersed among the elastic fibers were modified fibroblasts. These cells exhibited an irregular contour with numerous cytoplasmic processes and indentations. Their cytoplasm contained abundant rough endoplasmic reticulum, prominent Golgi complexes, and bundles of filaments. In the extracellular space, elastic fibers were often closely apposed to the plasma membrane of the fibroblasts. Carcinoma cells were also observed in the elastic tissue. It is postulated that fibroblasts, probably under an inductive influence from cancer cells, are the cells responsible for elastic production."} {"id": "PMID:174799", "title": "An ultrastructural study of nine thymomas.", "content": "Nine thymomas, a normal adult thymus, and tissue culture of one thymoma were studied ultrastructurally. The histologic types of thymoma included lymphocytic, epithelial, mixed and spindle cell varieties. Two of the tumors were invasive and one was associated with myasthenia gravis. Despite the histologic dissimilarities, the complex anatomic interrelationships involving lymphocytes, epithelial cells, and blood vessels as seen in the thymus tended to be preserved in all but one of the thymomas. The exception was the spindle-cell thymoma which contained only rare lymphocytes and simpler vascular structures. The findings include variations in the frequency of demosomes and cytoplasmic fibrils of the epithelial cells, the occasional presence of lymphocytes within the laminated venules, and the unusual finding of a gland-like structure in one of the tumors. Correlations between ultrastructural changes and clinical behavior could not be made.", "contents": "An ultrastructural study of nine thymomas. Nine thymomas, a normal adult thymus, and tissue culture of one thymoma were studied ultrastructurally. The histologic types of thymoma included lymphocytic, epithelial, mixed and spindle cell varieties. Two of the tumors were invasive and one was associated with myasthenia gravis. Despite the histologic dissimilarities, the complex anatomic interrelationships involving lymphocytes, epithelial cells, and blood vessels as seen in the thymus tended to be preserved in all but one of the thymomas. The exception was the spindle-cell thymoma which contained only rare lymphocytes and simpler vascular structures. The findings include variations in the frequency of demosomes and cytoplasmic fibrils of the epithelial cells, the occasional presence of lymphocytes within the laminated venules, and the unusual finding of a gland-like structure in one of the tumors. Correlations between ultrastructural changes and clinical behavior could not be made."} {"id": "PMID:174800", "title": "Ultrastructural study of the pineal germinoma in vivo and in vitro.", "content": "The fine structure of a pineal germinoma was studied in tissue blocks and in tissue culture. The original tumor contained large primary tumor cells, lymphocytes, macrophages, plasma cells, and astrocytes. The large primary tumor cells were characterized by large nuclei, relatively scanty organelles, abundant glycogen, and junctional complexes. The neoplasm grew well in vitro and, with the exception of plasma cells, contained the same cell types found in vivo. The ultrastructural characteristics of the cells in vivo and in vitro were similar. In culture there were few large primary tumor cells. Macrophages, often involved in active phagocytosis, were prominent in the original tumor and were the most common cell type found in vitro. A tumor-associated immune response is postulated in this neoplasm.", "contents": "Ultrastructural study of the pineal germinoma in vivo and in vitro. The fine structure of a pineal germinoma was studied in tissue blocks and in tissue culture. The original tumor contained large primary tumor cells, lymphocytes, macrophages, plasma cells, and astrocytes. The large primary tumor cells were characterized by large nuclei, relatively scanty organelles, abundant glycogen, and junctional complexes. The neoplasm grew well in vitro and, with the exception of plasma cells, contained the same cell types found in vivo. The ultrastructural characteristics of the cells in vivo and in vitro were similar. In culture there were few large primary tumor cells. Macrophages, often involved in active phagocytosis, were prominent in the original tumor and were the most common cell type found in vitro. A tumor-associated immune response is postulated in this neoplasm."} {"id": "PMID:174801", "title": "Elastogenesis in adenomatoid tumor: histochemical and ultrastructural observations.", "content": "An adenomatoid tumor from the round ligament of a 50-year-old woman was studied by light and electron microscopy. Ultrastructurally the tumor was remarkably similar to normal as well as neoplastic mesothelium, thus lending further support to the concept of a mesothelial origin of adenomatoid tumors. Comparative histochemical and ultrastructural studies revealed presence of acid mucopolysaccharides mainly along the luminal borders of the tumor cells, thus indicating likely production of this material by the tumor cells as opposed to the stromal cells. The stroma was rich in elastic fibers and there was evidence of active elastogenesis. This paper represents the first unequivocal demonstration of elastogenesis in an adenomatoid tumor.", "contents": "Elastogenesis in adenomatoid tumor: histochemical and ultrastructural observations. An adenomatoid tumor from the round ligament of a 50-year-old woman was studied by light and electron microscopy. Ultrastructurally the tumor was remarkably similar to normal as well as neoplastic mesothelium, thus lending further support to the concept of a mesothelial origin of adenomatoid tumors. Comparative histochemical and ultrastructural studies revealed presence of acid mucopolysaccharides mainly along the luminal borders of the tumor cells, thus indicating likely production of this material by the tumor cells as opposed to the stromal cells. The stroma was rich in elastic fibers and there was evidence of active elastogenesis. This paper represents the first unequivocal demonstration of elastogenesis in an adenomatoid tumor."} {"id": "PMID:174802", "title": "Gastric carcinoid with ectopic production of ACTH and beta-MSH.", "content": "A 51-year-old woman with typical Cushing's syndrome of about 9 years duration was shown to have a gastric carcinoid tumor. Plasma levels of ACTH and cortisol were elevated and lacked the normal diurnal rhythm. Urinary excretion of steroids was unaffected by the administration of either metyrapone or dexamethasone. Fluctuation in urinary steroid excretion, as well as transient hypokalemic alkalosis and glycosuria suggested periodic hormonogenesis. The extirpated gastric carcinoid was shown to contain immunoreactive ACTH and beta-MSH. However, the biologic ACTH activity was undetectable by in vivo steroidogenic assay. By gel filtration, it was demonstrated that both tumor and plasma ACTH was predominately \"big\" ACTH. Although postoperatively she developed hypoadrenocorticism severe enough to require ACTH treatment, her pituitary-adrenal function was gradually restored. This is the first documented case of ectopic ACTH syndrome caused by gastric carcinoid in which successful cure was achieved by surgery.", "contents": "Gastric carcinoid with ectopic production of ACTH and beta-MSH. A 51-year-old woman with typical Cushing's syndrome of about 9 years duration was shown to have a gastric carcinoid tumor. Plasma levels of ACTH and cortisol were elevated and lacked the normal diurnal rhythm. Urinary excretion of steroids was unaffected by the administration of either metyrapone or dexamethasone. Fluctuation in urinary steroid excretion, as well as transient hypokalemic alkalosis and glycosuria suggested periodic hormonogenesis. The extirpated gastric carcinoid was shown to contain immunoreactive ACTH and beta-MSH. However, the biologic ACTH activity was undetectable by in vivo steroidogenic assay. By gel filtration, it was demonstrated that both tumor and plasma ACTH was predominately \"big\" ACTH. Although postoperatively she developed hypoadrenocorticism severe enough to require ACTH treatment, her pituitary-adrenal function was gradually restored. This is the first documented case of ectopic ACTH syndrome caused by gastric carcinoid in which successful cure was achieved by surgery."} {"id": "PMID:174803", "title": "Congenital anomalies in children with Wilms' tumor: a new survey.", "content": "From 68 hospitals in the National Wilms' Tumor Study, records of 547 patients showed six patients with aniridia, 16 with hemihypertrophy, and 24 with genitourinary abnormalities. Multiple cases of Wilms' tumor occurred in three families. The results confirm high frequencies of aniridia and genitourinary anomalies in patients with Wilms' tumor, and show that concurrence with hemihypertrophy may be more often recognized or recorded now than it was ten years ago. The results demonstrate the desirability of developing checklists for other childhood neoplasms some of which have their own constellation of anomalies.", "contents": "Congenital anomalies in children with Wilms' tumor: a new survey. From 68 hospitals in the National Wilms' Tumor Study, records of 547 patients showed six patients with aniridia, 16 with hemihypertrophy, and 24 with genitourinary abnormalities. Multiple cases of Wilms' tumor occurred in three families. The results confirm high frequencies of aniridia and genitourinary anomalies in patients with Wilms' tumor, and show that concurrence with hemihypertrophy may be more often recognized or recorded now than it was ten years ago. The results demonstrate the desirability of developing checklists for other childhood neoplasms some of which have their own constellation of anomalies."} {"id": "PMID:174804", "title": "Peptide hormones as tumor markers.", "content": "Ectopic production and secretion of hormones by a wide variety of tumors were initially recognized by signs and symptoms of excess circulating biologically active hormone. With the development of more sophisticated and sensitive techniques, it has become apparent that not all tumors secrete biologically active hormones. Some altered forms of polypeptide hormones may be in very high concentrations immunologically but be inactive biologically. On the other hand, polypeptide hormones may circulate at concentrations too low to induce clinical signs and symptoms. Consequently, new ectopic humoral syndromes have been recognized and the incidence of previously described syndromes has become considerably greater than previously recognized. Every hormone known to be normally secreted by endocrine organs or the placenta has been documented to be secreted ectopically by a wide variety of tumors. Moreover, several of those hormones may be used as biochemical markers of malignancy for both screening and monitoring of patients with documented or suspected tumors.", "contents": "Peptide hormones as tumor markers. Ectopic production and secretion of hormones by a wide variety of tumors were initially recognized by signs and symptoms of excess circulating biologically active hormone. With the development of more sophisticated and sensitive techniques, it has become apparent that not all tumors secrete biologically active hormones. Some altered forms of polypeptide hormones may be in very high concentrations immunologically but be inactive biologically. On the other hand, polypeptide hormones may circulate at concentrations too low to induce clinical signs and symptoms. Consequently, new ectopic humoral syndromes have been recognized and the incidence of previously described syndromes has become considerably greater than previously recognized. Every hormone known to be normally secreted by endocrine organs or the placenta has been documented to be secreted ectopically by a wide variety of tumors. Moreover, several of those hormones may be used as biochemical markers of malignancy for both screening and monitoring of patients with documented or suspected tumors."} {"id": "PMID:174805", "title": "Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate.", "content": "The epidemiological studies suggest that aflatoxins, the toxic metabolites of the ubiquitous mold Aspergillus flavus, may play a significant role in the evolution of hepatocellular carcinoma in man in certain geographic areas of the world. To ascertain their carcinogenicity in nonhuman primates, we have administered highly purified aflatoxin B1, intermittently in the diet at 2 ppm, to 10 female and 8 male tree shrews. The tree shrew (Tupaia glis) is a nonhuman primate occurring throughout Southeast Asia which can be reared easily in captivity. Of 12 animals that survived, 6 of 6 female (100%) and 3 of 6 male (50%) tree shrews developed hepatocellular carcinomas between 74 and 172 weeks after the beginning of the experiment. None of the 8 control animals developed liver cancers. The estimated total amount of aflatoxin B1 consumed by these animals ranged from 24 to 66 mg. The development of liver tumors did not follow a specific pattern; considerable variation in hepatocellular responses to aflatoxin B1 was noted in these animals. In 2 tree shrews, the liver tumors were associated with severe post necrotic scarring; in the other 7 tumor-bearing livers, only mild to moderate portal fibrosis was encountered. This individual variation in hepatocellular response and in the amount of aflatoxin B1 required to induce hepatocellular carcinomas is attributed to inherent differences in the susceptibility within a given species of outbred animals and suggests extreme caution in proposing the \"permissible\" or \"safe\" levels of contamination of carcinogens in the food-stuffs.", "contents": "Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate. The epidemiological studies suggest that aflatoxins, the toxic metabolites of the ubiquitous mold Aspergillus flavus, may play a significant role in the evolution of hepatocellular carcinoma in man in certain geographic areas of the world. To ascertain their carcinogenicity in nonhuman primates, we have administered highly purified aflatoxin B1, intermittently in the diet at 2 ppm, to 10 female and 8 male tree shrews. The tree shrew (Tupaia glis) is a nonhuman primate occurring throughout Southeast Asia which can be reared easily in captivity. Of 12 animals that survived, 6 of 6 female (100%) and 3 of 6 male (50%) tree shrews developed hepatocellular carcinomas between 74 and 172 weeks after the beginning of the experiment. None of the 8 control animals developed liver cancers. The estimated total amount of aflatoxin B1 consumed by these animals ranged from 24 to 66 mg. The development of liver tumors did not follow a specific pattern; considerable variation in hepatocellular responses to aflatoxin B1 was noted in these animals. In 2 tree shrews, the liver tumors were associated with severe post necrotic scarring; in the other 7 tumor-bearing livers, only mild to moderate portal fibrosis was encountered. This individual variation in hepatocellular response and in the amount of aflatoxin B1 required to induce hepatocellular carcinomas is attributed to inherent differences in the susceptibility within a given species of outbred animals and suggests extreme caution in proposing the \"permissible\" or \"safe\" levels of contamination of carcinogens in the food-stuffs."} {"id": "PMID:174806", "title": "C-type virus particles in urethan-induced pulmonary and renal carcinomas, in cell-graft-transmitted carcinosarcomas, and in filtrate-induced lymphomas in mice.", "content": "Repeated injections of urethan into suckling BALB/c mice induced multiple papillary adenocarcinomas in the lungs and kidneys. When the pulmonary tumors were transplanted i.p. by cell graft into 6 suckling BALB/c mice, they induced disseminated carcinosarcomas within the peritoneal cavity in all inoculated animals. Tumors resulting from the transplantation of tumor cells were used for preparation of filtered extracts. The filtrates were inoculated into 6 suckling BALB/c mice and induced generalized malignant lymphomas in all animals. The primary urethan-induced pulmonary and renal tumors, the carcinosarcomas that resulted from i.p. cell transfer, and also the generalized malignant lymphomas induced by inoculation of filtered extracts contained C-type virus particles. Theoretically, it could be assumed that both the primary urethan-induced pulmonary and renal tumors, as well as the cell-graft-induced peritoneal carcinosarcomas, contained the C-type virus particles as passengers, not necessarily related etiologically to the tumors in which they were found. It is quite likely, however, that these virus particles were etiologically related to the filtrate-induced malignant lymphomas in which they were also found.", "contents": "C-type virus particles in urethan-induced pulmonary and renal carcinomas, in cell-graft-transmitted carcinosarcomas, and in filtrate-induced lymphomas in mice. Repeated injections of urethan into suckling BALB/c mice induced multiple papillary adenocarcinomas in the lungs and kidneys. When the pulmonary tumors were transplanted i.p. by cell graft into 6 suckling BALB/c mice, they induced disseminated carcinosarcomas within the peritoneal cavity in all inoculated animals. Tumors resulting from the transplantation of tumor cells were used for preparation of filtered extracts. The filtrates were inoculated into 6 suckling BALB/c mice and induced generalized malignant lymphomas in all animals. The primary urethan-induced pulmonary and renal tumors, the carcinosarcomas that resulted from i.p. cell transfer, and also the generalized malignant lymphomas induced by inoculation of filtered extracts contained C-type virus particles. Theoretically, it could be assumed that both the primary urethan-induced pulmonary and renal tumors, as well as the cell-graft-induced peritoneal carcinosarcomas, contained the C-type virus particles as passengers, not necessarily related etiologically to the tumors in which they were found. It is quite likely, however, that these virus particles were etiologically related to the filtrate-induced malignant lymphomas in which they were also found."} {"id": "PMID:174807", "title": "Distribution of viral glycoprotein gp 69/71 on cell surfaces of producer and nonproducer cells.", "content": "The distribution of the viral glycoprotein, gp 69/71, was studied on the cell surfaces of virus-producing and nonproducing cells. gp 69/71 was distributed evenly on cell membranes and on viral membranes of cells producing murine leukemia virus. gp 69/71 was distributed uniformly on cell membranes of thymocytes from NZB and strain 129 mice but was not detected on cell membranes of BALB/c thymocytes. Viral particles were associated with NZB and BALB/c thymocytes but were not in or on 129 thymocytes. We conclude that the presence of gp 69/71 on thymocyte membranes is not related to virus production. In the strains showing gp 69/71 on their thymocyte surfaces (NZB and 129), a large percentage of the thymocytes are positively labeled, all more or less equally. Immunochemical analysis of cell surface proteins labeled with 125I corroborated the ultrastructural observations. Thus, gp 69/71 can be expressed on the surface of thymocytes independently of virus particle production.", "contents": "Distribution of viral glycoprotein gp 69/71 on cell surfaces of producer and nonproducer cells. The distribution of the viral glycoprotein, gp 69/71, was studied on the cell surfaces of virus-producing and nonproducing cells. gp 69/71 was distributed evenly on cell membranes and on viral membranes of cells producing murine leukemia virus. gp 69/71 was distributed uniformly on cell membranes of thymocytes from NZB and strain 129 mice but was not detected on cell membranes of BALB/c thymocytes. Viral particles were associated with NZB and BALB/c thymocytes but were not in or on 129 thymocytes. We conclude that the presence of gp 69/71 on thymocyte membranes is not related to virus production. In the strains showing gp 69/71 on their thymocyte surfaces (NZB and 129), a large percentage of the thymocytes are positively labeled, all more or less equally. Immunochemical analysis of cell surface proteins labeled with 125I corroborated the ultrastructural observations. Thus, gp 69/71 can be expressed on the surface of thymocytes independently of virus particle production."} {"id": "PMID:174808", "title": "Generation and compensation of the cancer cachectic process by spontaneous modification of feeding behavior.", "content": "Daily food intake and corresponding feeding activity (measured as duration) and feeding efficiency (amount of food ingested per unit of feeding activity) were measured both in normal Sprague-Dawley and Buffalo rats and during growth of Walker 256 and 4M mammary carcinomas in Sprague-Dawley rats and of Morris 5123 hepatoma in Buffalo rats. Estimates of meal size and frequency were also obtained. Growth of the carcinomas produced a decline in feeding activity accompanied, early in tumor growth, by a compensatory increase in feeding efficiency with no resultant effect on food intake. This compensated decline in feeding activity was due to reduction in average meal duration. Later, meal frequency was also reduced, with further reduction in feeding activity and reduction in food intake. There was little change in average meal size. The hepatoma produced a different detailed pattern of effect on feeding behavior. These effects are not nonspecific reactions to foreign tissue. The effects imply behavioral compensation for the breakdown of a rapidly responding physiological control of food intake and can be interpreted in terms of successive impairment of feeding control mechanisms that have different response rates and different behavioral modes.", "contents": "Generation and compensation of the cancer cachectic process by spontaneous modification of feeding behavior. Daily food intake and corresponding feeding activity (measured as duration) and feeding efficiency (amount of food ingested per unit of feeding activity) were measured both in normal Sprague-Dawley and Buffalo rats and during growth of Walker 256 and 4M mammary carcinomas in Sprague-Dawley rats and of Morris 5123 hepatoma in Buffalo rats. Estimates of meal size and frequency were also obtained. Growth of the carcinomas produced a decline in feeding activity accompanied, early in tumor growth, by a compensatory increase in feeding efficiency with no resultant effect on food intake. This compensated decline in feeding activity was due to reduction in average meal duration. Later, meal frequency was also reduced, with further reduction in feeding activity and reduction in food intake. There was little change in average meal size. The hepatoma produced a different detailed pattern of effect on feeding behavior. These effects are not nonspecific reactions to foreign tissue. The effects imply behavioral compensation for the breakdown of a rapidly responding physiological control of food intake and can be interpreted in terms of successive impairment of feeding control mechanisms that have different response rates and different behavioral modes."} {"id": "PMID:174809", "title": "Characterization of growth properties and demonstration of the tumor-specific transplantation antigens of Morris hepatomas.", "content": "The growth properties of single-tumor-cell suspensions prepared by enzymatic digestion of solid tumors from Morris hepatomas 7777, 5123tc, and 3924a and the presence of tumor-specific transplantation antigen for tumor lines 7777 and 3924a were described. Two of the tumor cell lines (7777 and 3924a) showed consistent i.m. tumor growth following the inoculation of 1 x 10(5) tumor cells, and a similar dose of 5123tc tumor cells resulted in inconsistent tumor growth. Two of the tumor lines (5123tc and 7777) were associated with rapid appearance of lung metastases, whereas with line 3924a metastatic lung lesions rarely developed despite its rapid i.m. tumor growth rate. Tumor resistance to rechallenge with a threshold inoculum of tumor cells was present in approximately 15 to 50% of the animals following amputation of an existing tumor mass. Resistance to a challenge tumor cell inoculum could also be accomplished by immunization with irradiated tumor cells. Tumor-specific resistance was demonstrated to tumor line 3924a in that \"immune\" animals were able to resist a challenge with 3924a tumor cells but did not resist a challenge with tumor line 9098.", "contents": "Characterization of growth properties and demonstration of the tumor-specific transplantation antigens of Morris hepatomas. The growth properties of single-tumor-cell suspensions prepared by enzymatic digestion of solid tumors from Morris hepatomas 7777, 5123tc, and 3924a and the presence of tumor-specific transplantation antigen for tumor lines 7777 and 3924a were described. Two of the tumor cell lines (7777 and 3924a) showed consistent i.m. tumor growth following the inoculation of 1 x 10(5) tumor cells, and a similar dose of 5123tc tumor cells resulted in inconsistent tumor growth. Two of the tumor lines (5123tc and 7777) were associated with rapid appearance of lung metastases, whereas with line 3924a metastatic lung lesions rarely developed despite its rapid i.m. tumor growth rate. Tumor resistance to rechallenge with a threshold inoculum of tumor cells was present in approximately 15 to 50% of the animals following amputation of an existing tumor mass. Resistance to a challenge tumor cell inoculum could also be accomplished by immunization with irradiated tumor cells. Tumor-specific resistance was demonstrated to tumor line 3924a in that \"immune\" animals were able to resist a challenge with 3924a tumor cells but did not resist a challenge with tumor line 9098."} {"id": "PMID:174810", "title": "Altered microfilament structure in cells transformed with a temperature-sensitive transformation mutant of murine sarcoma virus.", "content": "The structure and distribution of microfilaments were examined by electron microscopy in uninfected normal rat kidney (NRK) cells, murine sarcoma virus (MSV)-transformed NRK cells, and NRK cells infected with a cold-sensitive transformation mutant of MSV, i.e., NRK (MSV-1b) cells, grown at both permissive (39 degrees) and nonpermissive (33 degrees) temperature. The uninfected cells contained numerous microfilaments which were especially prominent at sites of intercellular adherens junctions. In contrast, the MSV-transformed cells contained few microfilaments and did not form adherens junctions. At 33 degrees, the NRK (MSV-1b) cells appeared normal but formed an altered form of adherens junction with disorganized microfilaments. At 39 degrees, these cells resembled NRK cells transformed by wild-type MSV but still formed a few of the altered type of adherens junctions. Disorganized adherens junction microfilaments were also found in cells newly infected with wild-type MSV. These results suggest that the perturbed assembly of microfilaments at adherens junctions may be an intermediate stage in the loss of adherens junctions during viral transformation.", "contents": "Altered microfilament structure in cells transformed with a temperature-sensitive transformation mutant of murine sarcoma virus. The structure and distribution of microfilaments were examined by electron microscopy in uninfected normal rat kidney (NRK) cells, murine sarcoma virus (MSV)-transformed NRK cells, and NRK cells infected with a cold-sensitive transformation mutant of MSV, i.e., NRK (MSV-1b) cells, grown at both permissive (39 degrees) and nonpermissive (33 degrees) temperature. The uninfected cells contained numerous microfilaments which were especially prominent at sites of intercellular adherens junctions. In contrast, the MSV-transformed cells contained few microfilaments and did not form adherens junctions. At 33 degrees, the NRK (MSV-1b) cells appeared normal but formed an altered form of adherens junction with disorganized microfilaments. At 39 degrees, these cells resembled NRK cells transformed by wild-type MSV but still formed a few of the altered type of adherens junctions. Disorganized adherens junction microfilaments were also found in cells newly infected with wild-type MSV. These results suggest that the perturbed assembly of microfilaments at adherens junctions may be an intermediate stage in the loss of adherens junctions during viral transformation."} {"id": "PMID:174811", "title": "Effect of neuraminidase and papain treatment on lectin-induced agglutination of Novikoff tumor cells and assay of lectin receptor activity of the glycopeptides released from the cell surface by papain.", "content": "Lectins, plant proteins that bind specific saccharide determinants, have been utilized to examine the effect of neuraminidase digestion on the structure and/or expression of oligosaccharide moieties present at the periphery of Novikoff ascites hepatoma cells. Five lectins were utilized: concanavalin A (Con A), specific for alpha-D-manno- or alpha-D-glucopyranosyl residues; wheat germ agglutinin, specific for 2-acetamido-2-deoxy-D-glucopyranosyl residues; Ricinus communis agglutinin I (RCAI), specific for D-glucopyranosyl residues; R. communis agglutinin II (RCAII), specific for D-galacto- or 2-acetamido-2-deoxy-D-galactopyranosyl residues; and soybean agglutinin, specific for 2-acetamido-2-deoxy-D-galactopyranosyl residues. Neuraminidase treatment of Novikoff cells did not alter their agglutination by Con A or wheat germ agglutinin. Similar treatment produced only a 2-fold increase in their agglutination by RCAI but a 12-fold increase in their agglutination by RCAII, indicating that 2-acetamido-2-deoxy-D-galactopyranosyl residues become expressed upon neuraminidase treatment. This conclusion was confirmed by the observation that neuraminidase-treated Novikoff cells acquired agglutinability by soybean agglutinin. Binding studies using ferritin-conjugated RCAII indicated that neuraminidase treatment exposed cryptic cell surface receptors for RCAII. To ascertain the role of cell surface glycoproteins in lectin-induced agglutination of Novikoff cells, glycopeptides cleaved from the cell surface by papain were assayed for lectin receptor activity. The cell surface glycopeptides exhibited receptor activity for Con A, wheat germ agglutinin and RCAI but not for RCAII and soybean agglutinin. A cell surface macrosialoglycopeptide fraction, resolved by gel filtration and ion-exchange chromatography, possessed a major portion of the Con A and RCAI receptor activity.", "contents": "Effect of neuraminidase and papain treatment on lectin-induced agglutination of Novikoff tumor cells and assay of lectin receptor activity of the glycopeptides released from the cell surface by papain. Lectins, plant proteins that bind specific saccharide determinants, have been utilized to examine the effect of neuraminidase digestion on the structure and/or expression of oligosaccharide moieties present at the periphery of Novikoff ascites hepatoma cells. Five lectins were utilized: concanavalin A (Con A), specific for alpha-D-manno- or alpha-D-glucopyranosyl residues; wheat germ agglutinin, specific for 2-acetamido-2-deoxy-D-glucopyranosyl residues; Ricinus communis agglutinin I (RCAI), specific for D-glucopyranosyl residues; R. communis agglutinin II (RCAII), specific for D-galacto- or 2-acetamido-2-deoxy-D-galactopyranosyl residues; and soybean agglutinin, specific for 2-acetamido-2-deoxy-D-galactopyranosyl residues. Neuraminidase treatment of Novikoff cells did not alter their agglutination by Con A or wheat germ agglutinin. Similar treatment produced only a 2-fold increase in their agglutination by RCAI but a 12-fold increase in their agglutination by RCAII, indicating that 2-acetamido-2-deoxy-D-galactopyranosyl residues become expressed upon neuraminidase treatment. This conclusion was confirmed by the observation that neuraminidase-treated Novikoff cells acquired agglutinability by soybean agglutinin. Binding studies using ferritin-conjugated RCAII indicated that neuraminidase treatment exposed cryptic cell surface receptors for RCAII. To ascertain the role of cell surface glycoproteins in lectin-induced agglutination of Novikoff cells, glycopeptides cleaved from the cell surface by papain were assayed for lectin receptor activity. The cell surface glycopeptides exhibited receptor activity for Con A, wheat germ agglutinin and RCAI but not for RCAII and soybean agglutinin. A cell surface macrosialoglycopeptide fraction, resolved by gel filtration and ion-exchange chromatography, possessed a major portion of the Con A and RCAI receptor activity."} {"id": "PMID:174812", "title": "Breakage of human cell DNA after exposure to 3-methylcholanthrene-11,12-oxide.", "content": "Damage to and repair of DNA isolated from human neonatal and fetal skin cells were measured by alkaline sucrose gradient analysis. 3-Methylcholanthrene did not induce single-strand breaks in DNA of the cells in culture, whereas the 11,12-oxide of 3-methylcholanthrene was very effective in this regard. The cis-1,2-dihydroxy, trans-11,12-dihydroxy, and cis-11,12-dihydroxy derivatives of 3-methylcholanthrene exerted little effect. The breaks in DNA caused by 3-methylcholanthrene oxide occurred during a 60-min incubation period and were repaired during the following 60 min. Methylmethane sulfonate also induced breaks in the DNA within 60 min.", "contents": "Breakage of human cell DNA after exposure to 3-methylcholanthrene-11,12-oxide. Damage to and repair of DNA isolated from human neonatal and fetal skin cells were measured by alkaline sucrose gradient analysis. 3-Methylcholanthrene did not induce single-strand breaks in DNA of the cells in culture, whereas the 11,12-oxide of 3-methylcholanthrene was very effective in this regard. The cis-1,2-dihydroxy, trans-11,12-dihydroxy, and cis-11,12-dihydroxy derivatives of 3-methylcholanthrene exerted little effect. The breaks in DNA caused by 3-methylcholanthrene oxide occurred during a 60-min incubation period and were repaired during the following 60 min. Methylmethane sulfonate also induced breaks in the DNA within 60 min."} {"id": "PMID:174813", "title": "Kinetic and regulatory properties of pyruvate dehydrogenase from Ehrlich ascites tumor cells.", "content": "Pyruvate dehydrogenase was partially purified from Ehrlich ascites tumor cell mitochondria and its kinetic properties were determined. The apparent KM values for pyruvate, nicotinamide adenine dinucleotide, and coenzyme A (CoA) were 46 muM, 110 muM, and 36 muM, respectively. Reduced nicotinamide adenine dinucleotide and acetyl-CoA inhibited enzyme activity competitively to nicotinamide adenine dinucleotide (Ki = 22 muM) and CoA (Ki = 58 muM), respectively. Copurified alpha-ketoglutarate dehydrogenase displayed apparent KM values for alpha-ketoglutarate, nicotinamide adenine dinucleotide, and CoA of 1.25 mM, 67 muM, and 50 muM, respectively. Pyruvate dehydrogenase, but not alpha-ketoglutarate dehydrogenase, was inactivated specifically by adenosine triphosphate with concomitant phosphorylation, and it was reactivated at 10 mM Mg2+ by a protein fraction separated from the complex during purification. The rate of inactivation was decreased by pyruvate or pyrophosphate. The existence of active and inactive forms of pyruvate dehydrogenase in Ehrlich ascites tumor cells was demonstrated. Active form and total activity were determined to be 74.0 +/- 1.5 and 93.6 +/- 4.9 munits/g packed cells (mean +/- S.E., n = 25), respectively.", "contents": "Kinetic and regulatory properties of pyruvate dehydrogenase from Ehrlich ascites tumor cells. Pyruvate dehydrogenase was partially purified from Ehrlich ascites tumor cell mitochondria and its kinetic properties were determined. The apparent KM values for pyruvate, nicotinamide adenine dinucleotide, and coenzyme A (CoA) were 46 muM, 110 muM, and 36 muM, respectively. Reduced nicotinamide adenine dinucleotide and acetyl-CoA inhibited enzyme activity competitively to nicotinamide adenine dinucleotide (Ki = 22 muM) and CoA (Ki = 58 muM), respectively. Copurified alpha-ketoglutarate dehydrogenase displayed apparent KM values for alpha-ketoglutarate, nicotinamide adenine dinucleotide, and CoA of 1.25 mM, 67 muM, and 50 muM, respectively. Pyruvate dehydrogenase, but not alpha-ketoglutarate dehydrogenase, was inactivated specifically by adenosine triphosphate with concomitant phosphorylation, and it was reactivated at 10 mM Mg2+ by a protein fraction separated from the complex during purification. The rate of inactivation was decreased by pyruvate or pyrophosphate. The existence of active and inactive forms of pyruvate dehydrogenase in Ehrlich ascites tumor cells was demonstrated. Active form and total activity were determined to be 74.0 +/- 1.5 and 93.6 +/- 4.9 munits/g packed cells (mean +/- S.E., n = 25), respectively."} {"id": "PMID:174814", "title": "Cyclic nucleotide phosphodiesterases in neoplastic and nonneoplastic human mammary tissues.", "content": "Cyclic nucleotide phosphodiesterase activity was studied in 33 malignant neoplastic, 2 benign neoplastic, and 18 nonneoplastic human mammary tissues. Enzyme activity, using both cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monosphosphate as substrates, was measured in whole homogenates over a concentration range of 1 to 100 muM. Specific activity was calculated at substrate concentrations of 1 muM (low KM enzyme activity) and 100 muM (high KM activity). Diethylaminoethyl cellulose chromatography was used to separate the different enzyme species. The malignant neoplastic tissues had higher levels of both low-KM cyclic adenosine 3':5'-monophosphate and low-KM cyclic guanosine 3':5'-monophosphate phosphodiesterases. Further, the mean value of the ratio of low-km cyclic adenosine 3':5'-monophosphate to low-KM cyclic guanosine 3':5'-monophosphate activity was higher for the cancer tissues than for the nonneoplastic tissues. Diethylaminoethyl cellulose chromatography indicated the presence of three enzymes in both neoplastic and nonneoplastic mammary tissue. The kinetic as well as regulatory properties of the separated enzymes indicated that they are distinct enzyme activities. The phosphodiesterase properties were similar for neoplastic and nonneoplastic tissues and resembled those described previously in many other mammalian tissues. While both neoplastic and nonneoplastic tissues had detectable levels of the protein activator for phosphodiesterase, the cancer tissues appeared to have a higher level.", "contents": "Cyclic nucleotide phosphodiesterases in neoplastic and nonneoplastic human mammary tissues. Cyclic nucleotide phosphodiesterase activity was studied in 33 malignant neoplastic, 2 benign neoplastic, and 18 nonneoplastic human mammary tissues. Enzyme activity, using both cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monosphosphate as substrates, was measured in whole homogenates over a concentration range of 1 to 100 muM. Specific activity was calculated at substrate concentrations of 1 muM (low KM enzyme activity) and 100 muM (high KM activity). Diethylaminoethyl cellulose chromatography was used to separate the different enzyme species. The malignant neoplastic tissues had higher levels of both low-KM cyclic adenosine 3':5'-monophosphate and low-KM cyclic guanosine 3':5'-monophosphate phosphodiesterases. Further, the mean value of the ratio of low-km cyclic adenosine 3':5'-monophosphate to low-KM cyclic guanosine 3':5'-monophosphate activity was higher for the cancer tissues than for the nonneoplastic tissues. Diethylaminoethyl cellulose chromatography indicated the presence of three enzymes in both neoplastic and nonneoplastic mammary tissue. The kinetic as well as regulatory properties of the separated enzymes indicated that they are distinct enzyme activities. The phosphodiesterase properties were similar for neoplastic and nonneoplastic tissues and resembled those described previously in many other mammalian tissues. While both neoplastic and nonneoplastic tissues had detectable levels of the protein activator for phosphodiesterase, the cancer tissues appeared to have a higher level."} {"id": "PMID:174815", "title": "Croton oil- and benzo(a)pyrene-induced changes in cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate phosphodiesterase activities in mouse epidermis.", "content": "The topical application of croton oil, benzo(a)pyrene, acetic acid, and 12-O-tetradecanoyl-phorbol-13-acetate to mouse skin caused an increase in the activity of epidermal low-affinity cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase. The increase was most pronounced with croton oil, began between 4 and 6 hr after application of this material, and was maintained for at least 48 hr. The activity of cyclic guanosine 3':5'-monophosphate phosphodiesterase was also increased by treatment with croton oil or 12-O-tetradecanoyl-phorbol-13-acetate, but detailed time courses were not obtained. Increased activity was observed in both the soluble fractions and the washed particulate fractions of epidermis. Fractionation of soluble extracts from acetone-treated epidermis on DEAE-cellulose columns showed the presence of enzymes with specificity for both cyclic AMP and cyclic guanosine 3':5'-monophosphate, together with a peak catalyzing the hydrolysis of both cyclic AMP and cyclic guanosine 3':5'-monophosphate. The activity of this latter nonspecific activity was selectively increased following treatment with croton oil. The increase in cyclic AMP phosphodiesterase activity was partially abolished by multiple injections of cycloheximide, suggesting that new protein synthesis was involved. Injection of the alpha-receptor antagonist phentolamine abolished a croton oil-induced rise in epidermal cyclic AMP levels and decreased the induction of cyclic AMP phosphodiesterase activity. From these results it was concluded that the increase in enzyme activity was induced by cyclic AMP.", "contents": "Croton oil- and benzo(a)pyrene-induced changes in cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate phosphodiesterase activities in mouse epidermis. The topical application of croton oil, benzo(a)pyrene, acetic acid, and 12-O-tetradecanoyl-phorbol-13-acetate to mouse skin caused an increase in the activity of epidermal low-affinity cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase. The increase was most pronounced with croton oil, began between 4 and 6 hr after application of this material, and was maintained for at least 48 hr. The activity of cyclic guanosine 3':5'-monophosphate phosphodiesterase was also increased by treatment with croton oil or 12-O-tetradecanoyl-phorbol-13-acetate, but detailed time courses were not obtained. Increased activity was observed in both the soluble fractions and the washed particulate fractions of epidermis. Fractionation of soluble extracts from acetone-treated epidermis on DEAE-cellulose columns showed the presence of enzymes with specificity for both cyclic AMP and cyclic guanosine 3':5'-monophosphate, together with a peak catalyzing the hydrolysis of both cyclic AMP and cyclic guanosine 3':5'-monophosphate. The activity of this latter nonspecific activity was selectively increased following treatment with croton oil. The increase in cyclic AMP phosphodiesterase activity was partially abolished by multiple injections of cycloheximide, suggesting that new protein synthesis was involved. Injection of the alpha-receptor antagonist phentolamine abolished a croton oil-induced rise in epidermal cyclic AMP levels and decreased the induction of cyclic AMP phosphodiesterase activity. From these results it was concluded that the increase in enzyme activity was induced by cyclic AMP."} {"id": "PMID:174816", "title": "Limitations and utility of a cytolytic assay for measuring simian virus 40-induced cell surface antigens.", "content": "Antisera were produced against an SV40-transformed cell line in the syngeneic AL/N mouse. With a microcytolytic assay, the specificity of antisera produced by various immunization schedules and their ability to lyse numerous SV40-transformed cell lines were determined. Various AL/N mouse cell lines, newly transformed by SV40 and cloned, were found to be lysed by the antisera. When tumors were induced by SV40-transformed cells in the syngeneic mouse and cell lines were reestablished from tumors and such procedures were repeated, the susceptibility to serum-mediated cytolysis of the sublines was the same as that of the original SV40-transformed cell line, in spite of differences in tumorigenicity. Polyoma virus-transformed AL/N cell lines were also lysed while AL/N embryo cells, untransformed by SV40 or by polyoma, were not. SV40-transformed T-antigen-positive BALB/c mouse or hamster cell lines or a T-antigen-positive tissue cultured human cell were also resistant to lysis. A competition type of microassay demonstrated specific inhibition of the serum-mediated cytolysis by all of the SV40 T-antigen-positive cell lines tested. Thus, the lack of lysis of cells did not necessarily indicate the absence of SV40-induced surface antigens. The polyoma-transformed AL/N cell line also inhibited the antisera, but to a lesser extent, suggesting the possibility that SV40 and polyoma virus transformation may result in the appearance of partially common cell surface antigens.", "contents": "Limitations and utility of a cytolytic assay for measuring simian virus 40-induced cell surface antigens. Antisera were produced against an SV40-transformed cell line in the syngeneic AL/N mouse. With a microcytolytic assay, the specificity of antisera produced by various immunization schedules and their ability to lyse numerous SV40-transformed cell lines were determined. Various AL/N mouse cell lines, newly transformed by SV40 and cloned, were found to be lysed by the antisera. When tumors were induced by SV40-transformed cells in the syngeneic mouse and cell lines were reestablished from tumors and such procedures were repeated, the susceptibility to serum-mediated cytolysis of the sublines was the same as that of the original SV40-transformed cell line, in spite of differences in tumorigenicity. Polyoma virus-transformed AL/N cell lines were also lysed while AL/N embryo cells, untransformed by SV40 or by polyoma, were not. SV40-transformed T-antigen-positive BALB/c mouse or hamster cell lines or a T-antigen-positive tissue cultured human cell were also resistant to lysis. A competition type of microassay demonstrated specific inhibition of the serum-mediated cytolysis by all of the SV40 T-antigen-positive cell lines tested. Thus, the lack of lysis of cells did not necessarily indicate the absence of SV40-induced surface antigens. The polyoma-transformed AL/N cell line also inhibited the antisera, but to a lesser extent, suggesting the possibility that SV40 and polyoma virus transformation may result in the appearance of partially common cell surface antigens."} {"id": "PMID:174817", "title": "Brain tissue transplanted to the anterior chamber of the eye. 4. Drug-modulated transmitter release in central monoamine nerve terminals lacking normal postsynaptic receptors.", "content": "Small pieces of fetal rat brain selected to contain a high number of noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT) neuroblasts were transplanted to the anterior chamber of the eye of adult rats. The sympathetic ground plexus of the host iris was removed by superior cervical ganglionectomy so that transmitter mechanisms of the different central monoamine fibers innervating the iris could be selectively studied after intraocular maturation. Such irides, containing NA, DA, or 5-HT nerve terminals were incubated with radiolabelled transmitters and then stimulated by an electrical field while superfused, to investigate the spontaneous and stimulation-induced release of amine, both in drug-free buffer and buffer containing drugs acting on monoamine receptors. The central monoamine neurons of all three types were able to take up exogenous amines and release them upon stimulation by an electrical field, in much the same way as corresponding nerves in situ in slices of cerebral cortex (NA, 5-HT) or olfactory tubercle (DA). The alpha-adrenergic receptor blocking agent phentolamine increased the stimulation-induced release of 3H-NA from central NA fibers on the iris significantly. The dopamine receptor stimulating agent apomorphine decreased the stimulation-induced release of 3H-DA from central DA fibers on the iris. Pimozide, a DA receptor blocking drug tended to increase the 3H-DA release. The 5-HT receptor stimulating agent ergocornine tended to reduce the stimulation-induced release of 3H-5-HT from central 5-HT fibers on the iris. It was concluded that all three types of central monoamine nerve fibers develop essentially normal transmitter storage and release mechanisms also in an environment completely devoid of normal postsynaptic receptors. The drug experiments add strong support to the view that there are presynaptic monoamine receptors (\"autoreceptors\") able to modulate transmitter release present on the monoamine nerve terminals.", "contents": "Brain tissue transplanted to the anterior chamber of the eye. 4. Drug-modulated transmitter release in central monoamine nerve terminals lacking normal postsynaptic receptors. Small pieces of fetal rat brain selected to contain a high number of noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT) neuroblasts were transplanted to the anterior chamber of the eye of adult rats. The sympathetic ground plexus of the host iris was removed by superior cervical ganglionectomy so that transmitter mechanisms of the different central monoamine fibers innervating the iris could be selectively studied after intraocular maturation. Such irides, containing NA, DA, or 5-HT nerve terminals were incubated with radiolabelled transmitters and then stimulated by an electrical field while superfused, to investigate the spontaneous and stimulation-induced release of amine, both in drug-free buffer and buffer containing drugs acting on monoamine receptors. The central monoamine neurons of all three types were able to take up exogenous amines and release them upon stimulation by an electrical field, in much the same way as corresponding nerves in situ in slices of cerebral cortex (NA, 5-HT) or olfactory tubercle (DA). The alpha-adrenergic receptor blocking agent phentolamine increased the stimulation-induced release of 3H-NA from central NA fibers on the iris significantly. The dopamine receptor stimulating agent apomorphine decreased the stimulation-induced release of 3H-DA from central DA fibers on the iris. Pimozide, a DA receptor blocking drug tended to increase the 3H-DA release. The 5-HT receptor stimulating agent ergocornine tended to reduce the stimulation-induced release of 3H-5-HT from central 5-HT fibers on the iris. It was concluded that all three types of central monoamine nerve fibers develop essentially normal transmitter storage and release mechanisms also in an environment completely devoid of normal postsynaptic receptors. The drug experiments add strong support to the view that there are presynaptic monoamine receptors (\"autoreceptors\") able to modulate transmitter release present on the monoamine nerve terminals."} {"id": "PMID:174818", "title": "Cerebrospinal fluid-contacting neurons, ciliated perikarya and \"peptidergic\" synapses in the magnocellular preoptic nucleus of teleostean fishes.", "content": "The magnocellular preoptic nucleus of fishes (Anguilla anguilla, Amiurus nebulosus, Cyprinus carpio, Carassius auratus, Ctenopharyngodon idella, Cichlasoma nigrofasciatum) has been studied by light and electron microscopy. Two kinds of neurons Were found: a) large, electron-dense, Gomori-positive cells with moderate acetylcholinesterase (AChE) positivity which contain granulated vesicles of 1400 to 2200 A (in average 1600 to 1800 A), adn b) small, strongly AChE-positive, electron-lucent neurons containing granulated vesicles of 900 to 1200 A. The nerve cells are supplied with axo-somatic and axo-dendritic synapses. These are formed by axon terminals containing either 1. synaptic vesicles of 500 A, or 2. synaptic vesicles of 500 A and dense-core vesicles of 600 to 800 A, or 3. synaptic vesicles of 600 A and granulated vesicles of up to 1100 A, or 4. synaptic vesicles of about 400 A and granulated vesicles of up to 1800 A. The presence of \"peptidergic\" and numerous other synapses shows the complexity of the organization and afferentation of the magnocellular preoptic nucleus. In the eel, both types of nerve cells form dendritic terminals within the cerebrospinal fluid (CSF). These CSF contacting dendrites are supplied with 9 x 2 + 0 cilia. In the other species investigated, only some large neurons build up intraventricular endings. The ependymofugal process of the CSF contacting neurons enters the preoptic-neurohypophysial tract. Perikarya of both the large and the small cells may give rise to single, paired or multiple 9 x 2 + 0 cilia extending into the intercellular space. The number of CSF contacting neurons is reciprocal to the number of perikarya with intercellular cilium. These latter cells may represent modified, more differentiated forms of the CSF contacting neurons. We think that atypical cilia protruding into the intercellular space may have the same significance for the intercellular fluid as the cilia of the intraventricular dendrites of the CSF contacting neurons for the CSF.", "contents": "Cerebrospinal fluid-contacting neurons, ciliated perikarya and \"peptidergic\" synapses in the magnocellular preoptic nucleus of teleostean fishes. The magnocellular preoptic nucleus of fishes (Anguilla anguilla, Amiurus nebulosus, Cyprinus carpio, Carassius auratus, Ctenopharyngodon idella, Cichlasoma nigrofasciatum) has been studied by light and electron microscopy. Two kinds of neurons Were found: a) large, electron-dense, Gomori-positive cells with moderate acetylcholinesterase (AChE) positivity which contain granulated vesicles of 1400 to 2200 A (in average 1600 to 1800 A), adn b) small, strongly AChE-positive, electron-lucent neurons containing granulated vesicles of 900 to 1200 A. The nerve cells are supplied with axo-somatic and axo-dendritic synapses. These are formed by axon terminals containing either 1. synaptic vesicles of 500 A, or 2. synaptic vesicles of 500 A and dense-core vesicles of 600 to 800 A, or 3. synaptic vesicles of 600 A and granulated vesicles of up to 1100 A, or 4. synaptic vesicles of about 400 A and granulated vesicles of up to 1800 A. The presence of \"peptidergic\" and numerous other synapses shows the complexity of the organization and afferentation of the magnocellular preoptic nucleus. In the eel, both types of nerve cells form dendritic terminals within the cerebrospinal fluid (CSF). These CSF contacting dendrites are supplied with 9 x 2 + 0 cilia. In the other species investigated, only some large neurons build up intraventricular endings. The ependymofugal process of the CSF contacting neurons enters the preoptic-neurohypophysial tract. Perikarya of both the large and the small cells may give rise to single, paired or multiple 9 x 2 + 0 cilia extending into the intercellular space. The number of CSF contacting neurons is reciprocal to the number of perikarya with intercellular cilium. These latter cells may represent modified, more differentiated forms of the CSF contacting neurons. We think that atypical cilia protruding into the intercellular space may have the same significance for the intercellular fluid as the cilia of the intraventricular dendrites of the CSF contacting neurons for the CSF."} {"id": "PMID:174819", "title": "Effect of \"restricted ovulator\" gene on uptake of yolk-precursor protein.", "content": "The bulk of the yolk proteins and lipoproteins constituting the yolks of mature oocytes in birds are synthesized by the liver and transported via the plasma to the oocytes where they are incorporated by micropinocytosis. Evidence is presented indicating that oocytes of hens possessing a mutation identified by Jones, Briles, and Schjeide as a \"restricted ovulator gene\" fail to incorporate normal amounts and proportions of low density lipoproteins, lipovitellin and possible other proteins making up the bulk of the yolk material. Plasma albumin is taken into the yolks but the other proteins synthesized by the liver for deposition within the oocytes accumulate in the plasma, attaining very high levels. The possible nature of the \"lock\" preventing normal deposition of the excluded yolk proteins is discussed.", "contents": "Effect of \"restricted ovulator\" gene on uptake of yolk-precursor protein. The bulk of the yolk proteins and lipoproteins constituting the yolks of mature oocytes in birds are synthesized by the liver and transported via the plasma to the oocytes where they are incorporated by micropinocytosis. Evidence is presented indicating that oocytes of hens possessing a mutation identified by Jones, Briles, and Schjeide as a \"restricted ovulator gene\" fail to incorporate normal amounts and proportions of low density lipoproteins, lipovitellin and possible other proteins making up the bulk of the yolk material. Plasma albumin is taken into the yolks but the other proteins synthesized by the liver for deposition within the oocytes accumulate in the plasma, attaining very high levels. The possible nature of the \"lock\" preventing normal deposition of the excluded yolk proteins is discussed."} {"id": "PMID:174820", "title": "New ultrastructural features on the cream hamster thyroid with special reference to the second kind of follicle.", "content": "The thyroid cells of the cream hamster, characterized by abundance of microtubules and stratification of the organelles, undergo a particular evolution when the animals grow older. These changes are characterized by an increase of the number of lysosomes which in extreme cases become so prominent that they occupy the whole cytoplasm of the cell which thus loses its organelle stratification. As in other species, cream hamster thyroid contains so-called ultimobranchial follicles made up of at least six cell types: fibrillar dark and light cells, parafollicular cells, ciliated cells, vesicular cells, and cells with myelinic inclusions. The ultrastructure of these follicles in the cream hamster represents a mixture of the ultrastructural characteristics of the same follicles encountered in the rat and the mouse thyroid. Here also mixed follicles are seen. Nevertheless vesicular cells present such abundant \"secretion granules\" that the question arises as to whether these follicles produce a special secretion and perhaps a new hormone. Incubation of cream hamster thyroids in the prescence of vincristine induces vanishing of microtubules, formation of paracrystalline structures, and loss of stratification of the organelles. Although these last effects might be due to some specific toxic effect of the drug, it is suggested that the disappearing of the organelle stratification might result from a specific vincristine-induced disaggregation of the microtubules acting as a cytoskeleton.", "contents": "New ultrastructural features on the cream hamster thyroid with special reference to the second kind of follicle. The thyroid cells of the cream hamster, characterized by abundance of microtubules and stratification of the organelles, undergo a particular evolution when the animals grow older. These changes are characterized by an increase of the number of lysosomes which in extreme cases become so prominent that they occupy the whole cytoplasm of the cell which thus loses its organelle stratification. As in other species, cream hamster thyroid contains so-called ultimobranchial follicles made up of at least six cell types: fibrillar dark and light cells, parafollicular cells, ciliated cells, vesicular cells, and cells with myelinic inclusions. The ultrastructure of these follicles in the cream hamster represents a mixture of the ultrastructural characteristics of the same follicles encountered in the rat and the mouse thyroid. Here also mixed follicles are seen. Nevertheless vesicular cells present such abundant \"secretion granules\" that the question arises as to whether these follicles produce a special secretion and perhaps a new hormone. Incubation of cream hamster thyroids in the prescence of vincristine induces vanishing of microtubules, formation of paracrystalline structures, and loss of stratification of the organelles. Although these last effects might be due to some specific toxic effect of the drug, it is suggested that the disappearing of the organelle stratification might result from a specific vincristine-induced disaggregation of the microtubules acting as a cytoskeleton."} {"id": "PMID:174821", "title": "In vitro effects of histamine liberator compound 48/80 on rat superior cervical ganglia with special regard to the small granule-containing cells.", "content": "The effect of the histamine liberator compound 48/80 on the rat superior cervical ganglia in vitro has been investigated. After incubation of the ganglia with compound 48/80: (1) ganglionic mast cells degranulate in the same manner as in other tissues; (2) cell bodies of the postganglionic neurons are not affected by compound 48/80; (3) there is evidence that ganglionic interneurons, the monoamine-containing cells are activated. The ultrastructural aspects of this process are characterized by degranulation of perikarya and accumulation of dense core vesicles in cell processes and in terminals adjacent to presynaptic membranes. These vesicles vary in size between 200-800 A in diameter. They may represent storage sites of the neuro-transmitter complexes that have undergone exocytosis. The results are discussed with special reference to models of exocytotic processes involving the adrenergic transmitter. It is concluded that monoamine-containing cells represent interneurons in sympathetic ganglia which inhibit ganglionic transmission and which are stimulated by low concentrations of compound 48/80 in vitro.", "contents": "In vitro effects of histamine liberator compound 48/80 on rat superior cervical ganglia with special regard to the small granule-containing cells. The effect of the histamine liberator compound 48/80 on the rat superior cervical ganglia in vitro has been investigated. After incubation of the ganglia with compound 48/80: (1) ganglionic mast cells degranulate in the same manner as in other tissues; (2) cell bodies of the postganglionic neurons are not affected by compound 48/80; (3) there is evidence that ganglionic interneurons, the monoamine-containing cells are activated. The ultrastructural aspects of this process are characterized by degranulation of perikarya and accumulation of dense core vesicles in cell processes and in terminals adjacent to presynaptic membranes. These vesicles vary in size between 200-800 A in diameter. They may represent storage sites of the neuro-transmitter complexes that have undergone exocytosis. The results are discussed with special reference to models of exocytotic processes involving the adrenergic transmitter. It is concluded that monoamine-containing cells represent interneurons in sympathetic ganglia which inhibit ganglionic transmission and which are stimulated by low concentrations of compound 48/80 in vitro."} {"id": "PMID:174825", "title": "Antibody responses to a combination vaccine against Haemophilus influenzae type b, diphtheria, pertussis, and tetanus.", "content": "Forty-one children were studied in order to provide information on antibody responses to H. influenzae type b polyribophosphate (PRP), given in combination with diphtheria-pertussis-tetanus vaccine (DPT). When PRP was administered alone, 9 of 15 children demonstrated fourfold or greater increases in titres of anti-PRP antibody. In contrast, in the group receiving a combination vaccine consisting of DPT and PRP only 1 of 13 children showed a similar rise in anti-PRP antibody. It was concluded that, in the population studied, the combination vaccine was less effective than PRP alone. The reasons for this difference and its potential significance are discussed.", "contents": "Antibody responses to a combination vaccine against Haemophilus influenzae type b, diphtheria, pertussis, and tetanus. Forty-one children were studied in order to provide information on antibody responses to H. influenzae type b polyribophosphate (PRP), given in combination with diphtheria-pertussis-tetanus vaccine (DPT). When PRP was administered alone, 9 of 15 children demonstrated fourfold or greater increases in titres of anti-PRP antibody. In contrast, in the group receiving a combination vaccine consisting of DPT and PRP only 1 of 13 children showed a similar rise in anti-PRP antibody. It was concluded that, in the population studied, the combination vaccine was less effective than PRP alone. The reasons for this difference and its potential significance are discussed."} {"id": "PMID:174826", "title": "[Isoelectric variants of the principal polypeptide (p 30) of different strains of murine oncornaviruses].", "content": "The major murine oncornavirus polypeptide p 30 (30,000 daltons), which bears the conventional group-specific (gs) determinants, can be separated by isoelectric focusing into four classes, with isoelectric points (pI) of 5.5, 5.9, 6.7 and 7.1. All the Moloney stocks tested have a pI 5.9 p 30, while p 30's with three to four different pI values are found to coexist in other stocks, with the pI 6.7 form predominating in Gross virus stocks.", "contents": "[Isoelectric variants of the principal polypeptide (p 30) of different strains of murine oncornaviruses]. The major murine oncornavirus polypeptide p 30 (30,000 daltons), which bears the conventional group-specific (gs) determinants, can be separated by isoelectric focusing into four classes, with isoelectric points (pI) of 5.5, 5.9, 6.7 and 7.1. All the Moloney stocks tested have a pI 5.9 p 30, while p 30's with three to four different pI values are found to coexist in other stocks, with the pI 6.7 form predominating in Gross virus stocks."} {"id": "PMID:174827", "title": "[In vitro transmission of mouse leukemia virus to restrictive mouse cells: necessity for mixed infection by two different leukemia viruses].", "content": "The plaque formation of murine leukemia virus (MuLV) in non permissive mouse cells (N-tropic MuLV in B-type cells, or B-tropic MuLV in N-type cells) was increased by murine sarcoma virus whose plaque-forming activity was extremely low (MuSV XC-). The infection of N-tropic MuLV in B-type cells was increased by MuSV XC- propagated only in N-type cells but not in B-type cells, and the infection of B-tropic MuLV in N-type cells by MuSV XC- propagated only in B-type cells but not in N-type cells.", "contents": "[In vitro transmission of mouse leukemia virus to restrictive mouse cells: necessity for mixed infection by two different leukemia viruses]. The plaque formation of murine leukemia virus (MuLV) in non permissive mouse cells (N-tropic MuLV in B-type cells, or B-tropic MuLV in N-type cells) was increased by murine sarcoma virus whose plaque-forming activity was extremely low (MuSV XC-). The infection of N-tropic MuLV in B-type cells was increased by MuSV XC- propagated only in N-type cells but not in B-type cells, and the infection of B-tropic MuLV in N-type cells by MuSV XC- propagated only in B-type cells but not in N-type cells."} {"id": "PMID:174828", "title": "[Stimulation of SV40 virus replication in Chinese hamster kidney cells by treatment of the cells with mitomycin C].", "content": "The production of virions by Chinese hamster kidney cells infected with SV 40 DNA is increased 10 to 100 fold by mitomycin C treatment. This observation has been confirmed for different cell clones. The optimum concentration of mitomycin C has been determined.", "contents": "[Stimulation of SV40 virus replication in Chinese hamster kidney cells by treatment of the cells with mitomycin C]. The production of virions by Chinese hamster kidney cells infected with SV 40 DNA is increased 10 to 100 fold by mitomycin C treatment. This observation has been confirmed for different cell clones. The optimum concentration of mitomycin C has been determined."} {"id": "PMID:174829", "title": "[The peroxisomes of Triturus cristatus (amphibian, urodele) adrenal cortex cells: peroxisome number as a function of steroidogenic activity].", "content": "Peroxisomes are scarce in the poorly active interrenal cells of hypophysectomized animals; their number increases drastically in cells which are stimulated by corticotrophic factors. A precise correlation appears thus to exist between the steroidogenic activity of the interrenal cells and the number of peroxisomes in these cells.", "contents": "[The peroxisomes of Triturus cristatus (amphibian, urodele) adrenal cortex cells: peroxisome number as a function of steroidogenic activity]. Peroxisomes are scarce in the poorly active interrenal cells of hypophysectomized animals; their number increases drastically in cells which are stimulated by corticotrophic factors. A precise correlation appears thus to exist between the steroidogenic activity of the interrenal cells and the number of peroxisomes in these cells."} {"id": "PMID:174830", "title": "[Selection of cell lines resistant to ouabain from murine plasmacytoma MOPC 173. Cross resistance to cyclic AMP, theophylline, and concanavalin A].", "content": "Using ouabain as a selective agent, we obtained from a contact inhibited and a non contact inhibited cell layer derived from the same plasmocytoma, different resistant cell lines. All of them were ouabain resistant but were also able to grow in presence of normallly toxic levels of cAMP, theophylline and concanavalin A.", "contents": "[Selection of cell lines resistant to ouabain from murine plasmacytoma MOPC 173. Cross resistance to cyclic AMP, theophylline, and concanavalin A]. Using ouabain as a selective agent, we obtained from a contact inhibited and a non contact inhibited cell layer derived from the same plasmocytoma, different resistant cell lines. All of them were ouabain resistant but were also able to grow in presence of normallly toxic levels of cAMP, theophylline and concanavalin A."} {"id": "PMID:174831", "title": "[Purification and study of equine infectious anemia virus antigens, produced in vivo or in cultured cells].", "content": "The G and C antigens of equine infectious anemia virus have been produced in vivo and in infected cell culture, then they have been purified. Their physico-chemical properties have been determined, particularly their molecular weight, their sedimentation coefficient, their density and the iso electric point.", "contents": "[Purification and study of equine infectious anemia virus antigens, produced in vivo or in cultured cells]. The G and C antigens of equine infectious anemia virus have been produced in vivo and in infected cell culture, then they have been purified. Their physico-chemical properties have been determined, particularly their molecular weight, their sedimentation coefficient, their density and the iso electric point."} {"id": "PMID:174832", "title": "[Primary liver carcinogenesis induced by the pesticide 2-(4-tert-butylphenoxy0-1-methylethyl 2-chloroethyl sulphite (Aramite)].", "content": "Wistar rats were fed, during 56 weeks, a diet containing 5 g/kg of Aramite. At the end of the treatment, all the surviving animals show, on anatomo-pathological examination, malignant proliferation of the hepatic tissue and, in certain cases, of biliary ducts. This compound, proposed in the past as acaricide in agriculture, can thus be considered as a model substance for induction of malignant liver tumors.", "contents": "[Primary liver carcinogenesis induced by the pesticide 2-(4-tert-butylphenoxy0-1-methylethyl 2-chloroethyl sulphite (Aramite)]. Wistar rats were fed, during 56 weeks, a diet containing 5 g/kg of Aramite. At the end of the treatment, all the surviving animals show, on anatomo-pathological examination, malignant proliferation of the hepatic tissue and, in certain cases, of biliary ducts. This compound, proposed in the past as acaricide in agriculture, can thus be considered as a model substance for induction of malignant liver tumors."} {"id": "PMID:174833", "title": "Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon.", "content": "Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation.", "contents": "Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon. Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation."} {"id": "PMID:174834", "title": "The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.", "content": "To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.", "contents": "The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects. To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture."} {"id": "PMID:174835", "title": "Dual radionuclide study of myocardial infarction. Relationships between myocardial uptake of potassium-43, technetium-99m stannous pyrophosphate, regional myocardial blood flow and creatine phosphokinase depletion.", "content": "The dual radionuclide myocardial distributions of imaging agents potassium-43 (43K) and technetium-99m stannous pyrophosphate (99mTc-PYP) were studied in a 24-hour closed chest canine infarct preparation. In multiple myocardial biopsies in 20 dogs, tissue levels of both radionuclides were compared to either an index of tissue viability (myocardial creatine phosphokinase [CPK] depletion), or to estimates of regional myocardial blood flow as measured by the microsphere technique. Myocardial 43K uptake in the ischemic and infarcted zone correlated well with both CPK depletion (r = 0.73) and microsphere estimates of relative blood flow. The correlation with microspheres was excellent in the transmural sample (r = 0.93) as well as endocardial (r = 0.97) and epicardial (r = 0.86) portions. On the other hand, 99mTc-PYP myocardial uptake did not correlate with the extent of CPK depletion. Maximal uptake was frequently noted in border zones with only moderate CPK depletion, while lesser degrees of 99mTc-PYP uptake were noted in the central infarct zone where CPK activity was lowest. The relationship of 99mTc-PYP uptake to microsphere regional flow estimates demonstrated that 99mTc-PYP uptake was maximal at flows of 0.3 to 0.4 of normal. At lower flows, 99mTc-PYP uptake fell toward normal levels. A similar relationship was noted between the distributions of 99mTc-PYP and 43K. In relatively high flow border segments (larger than or equal to 0.80 of normal), abnormal 99mTc-PYP uptake of five to six times normal persisted. The transmural distribution of 99mTc-PYP demonstrated that in low flow regions 99mTc-PYP uptake was primarily epicardial, while in the higher flow ischemic periphery of the infarct endocardial uptake predominated. Thus, while there is a direct correlation between cationic 43K myocardial uptake and regional myocardial viability and blood flow, no such direct relationship exists for 99mTc-PYP. This is in part based on the necessity for delivery of the radioactive tracer to the infarct zone.", "contents": "Dual radionuclide study of myocardial infarction. Relationships between myocardial uptake of potassium-43, technetium-99m stannous pyrophosphate, regional myocardial blood flow and creatine phosphokinase depletion. The dual radionuclide myocardial distributions of imaging agents potassium-43 (43K) and technetium-99m stannous pyrophosphate (99mTc-PYP) were studied in a 24-hour closed chest canine infarct preparation. In multiple myocardial biopsies in 20 dogs, tissue levels of both radionuclides were compared to either an index of tissue viability (myocardial creatine phosphokinase [CPK] depletion), or to estimates of regional myocardial blood flow as measured by the microsphere technique. Myocardial 43K uptake in the ischemic and infarcted zone correlated well with both CPK depletion (r = 0.73) and microsphere estimates of relative blood flow. The correlation with microspheres was excellent in the transmural sample (r = 0.93) as well as endocardial (r = 0.97) and epicardial (r = 0.86) portions. On the other hand, 99mTc-PYP myocardial uptake did not correlate with the extent of CPK depletion. Maximal uptake was frequently noted in border zones with only moderate CPK depletion, while lesser degrees of 99mTc-PYP uptake were noted in the central infarct zone where CPK activity was lowest. The relationship of 99mTc-PYP uptake to microsphere regional flow estimates demonstrated that 99mTc-PYP uptake was maximal at flows of 0.3 to 0.4 of normal. At lower flows, 99mTc-PYP uptake fell toward normal levels. A similar relationship was noted between the distributions of 99mTc-PYP and 43K. In relatively high flow border segments (larger than or equal to 0.80 of normal), abnormal 99mTc-PYP uptake of five to six times normal persisted. The transmural distribution of 99mTc-PYP demonstrated that in low flow regions 99mTc-PYP uptake was primarily epicardial, while in the higher flow ischemic periphery of the infarct endocardial uptake predominated. Thus, while there is a direct correlation between cationic 43K myocardial uptake and regional myocardial viability and blood flow, no such direct relationship exists for 99mTc-PYP. This is in part based on the necessity for delivery of the radioactive tracer to the infarct zone."} {"id": "PMID:174836", "title": "Superoxide anions and other components of human renal adenocarcinoma.", "content": "The levels of superoxide anion production, cytochrome P450, ornithine decarboxylase(E.C.4.1.1.17), catalase(E.C.1.11.1.6), deoxyribonucleic acid, ribonucleic acid and protein have been studied in human kidney and renal clear-cell adenocarcinoma tissues. The levels of superoxide anion production, ornithine decarboxylase, catalase and ribonucleic acid in the tumor tissue are very different from those in the kidney.", "contents": "Superoxide anions and other components of human renal adenocarcinoma. The levels of superoxide anion production, cytochrome P450, ornithine decarboxylase(E.C.4.1.1.17), catalase(E.C.1.11.1.6), deoxyribonucleic acid, ribonucleic acid and protein have been studied in human kidney and renal clear-cell adenocarcinoma tissues. The levels of superoxide anion production, ornithine decarboxylase, catalase and ribonucleic acid in the tumor tissue are very different from those in the kidney."} {"id": "PMID:174837", "title": "Separation of A and E prostaglandins by celite partition chromatography for radioimmunoassay.", "content": "This report describes the use of celite partition chromatography to separate the A and E prostaglandins. The stationary phase consists of a glycine-HCL buffer, pH 3.6-3.7. The mobile phase consists of mixtures of ethyl acetate in toluene. At this critical hydrogen ion concentration of the stationary phase, the two prostaglandin groups are clearly separated on the basis of their difference in polarity, with greater than 95% recoveries and only 5% overlap of the elution patterns. It is anticipated that specific radioimmunoassays can be achieved by combining this system with partially specific antisera.", "contents": "Separation of A and E prostaglandins by celite partition chromatography for radioimmunoassay. This report describes the use of celite partition chromatography to separate the A and E prostaglandins. The stationary phase consists of a glycine-HCL buffer, pH 3.6-3.7. The mobile phase consists of mixtures of ethyl acetate in toluene. At this critical hydrogen ion concentration of the stationary phase, the two prostaglandin groups are clearly separated on the basis of their difference in polarity, with greater than 95% recoveries and only 5% overlap of the elution patterns. It is anticipated that specific radioimmunoassays can be achieved by combining this system with partially specific antisera."} {"id": "PMID:174838", "title": "Lipoprotein pre-staining: comparison of nitroblue tetrazolium and Sudan Black B.", "content": "Nitroblue tetrazolium and Sudan Black B have been compared as pre-staining agents for human serum lipoproteins, using acrylamide gel gradients. Results from Nitroblue tetrazolium staining should be used with caution for low and very low density lipoproteins, and further work appears necessary on the reaction with alpha-lipoproteins.", "contents": "Lipoprotein pre-staining: comparison of nitroblue tetrazolium and Sudan Black B. Nitroblue tetrazolium and Sudan Black B have been compared as pre-staining agents for human serum lipoproteins, using acrylamide gel gradients. Results from Nitroblue tetrazolium staining should be used with caution for low and very low density lipoproteins, and further work appears necessary on the reaction with alpha-lipoproteins."} {"id": "PMID:174839", "title": "[An immunoelectrophoretic study of plasma lipoproteins in a case of familial deficiency of lecithin-cholesterol acyltransferase (author's transl)].", "content": "The lipid composition and apopeptide patterns of plasma LDL and VLDL have been studied in a patient with LCAT deficiency, using two-dimensional immunoelectrophoresis. After absorption of a fat meal an elevation of VLDL apopeptides C was observed. Apo-LDL also showed an abnormal relative increase of apo-C. After heparin-induced lipolysis, a shift of apo-C from chylomicra and VLDL to LDL was noticed by the striking increase of apo-C in this last lipoprotein class. In view of the present and previously published results the possible mechanisms involved in lipoprotein catabolism in LCAT deficiency are discussed.", "contents": "[An immunoelectrophoretic study of plasma lipoproteins in a case of familial deficiency of lecithin-cholesterol acyltransferase (author's transl)]. The lipid composition and apopeptide patterns of plasma LDL and VLDL have been studied in a patient with LCAT deficiency, using two-dimensional immunoelectrophoresis. After absorption of a fat meal an elevation of VLDL apopeptides C was observed. Apo-LDL also showed an abnormal relative increase of apo-C. After heparin-induced lipolysis, a shift of apo-C from chylomicra and VLDL to LDL was noticed by the striking increase of apo-C in this last lipoprotein class. In view of the present and previously published results the possible mechanisms involved in lipoprotein catabolism in LCAT deficiency are discussed."} {"id": "PMID:174840", "title": "Urinary lactate excretion in normal children and in children with enzyme defects of carbohydrate metabolism.", "content": "Urinary lactate was analyzed in 53 normal children, 7 children with glucose-6-phosphatase-deficient glycogenosis, 1 child with fructose-1,6-diphosphatase deficiency and 1 child with pyruvate dehydrogenase deficiency. Lactate in 24-h urine was expressed as concentration, total excretion, excretion per kg body weight and per 1.73 m2 body surface, and as lactate/creatinine quotient. Of these parameters, the lactate concentration in 24-h urine showed the smallest variation in normal children (0.155 +/- 0.053 mM), whereas in patients with one of the above mentioned enzymopathies 10-300-fold elevations were found. The lactate/creatinine quotient, normal range 0.010 to 0.058 (mM/mM) was also used to correct for unnoticed losses of urine. Both parameters, used in conjunction with blood lactate analysis, are suitable for a first screening of patients with enzymopathies of carbohydrate metabolism, and for the follow-up study of the steady or unsteady state of the patient with an enzyme defect of carbohydrate metabolism.", "contents": "Urinary lactate excretion in normal children and in children with enzyme defects of carbohydrate metabolism. Urinary lactate was analyzed in 53 normal children, 7 children with glucose-6-phosphatase-deficient glycogenosis, 1 child with fructose-1,6-diphosphatase deficiency and 1 child with pyruvate dehydrogenase deficiency. Lactate in 24-h urine was expressed as concentration, total excretion, excretion per kg body weight and per 1.73 m2 body surface, and as lactate/creatinine quotient. Of these parameters, the lactate concentration in 24-h urine showed the smallest variation in normal children (0.155 +/- 0.053 mM), whereas in patients with one of the above mentioned enzymopathies 10-300-fold elevations were found. The lactate/creatinine quotient, normal range 0.010 to 0.058 (mM/mM) was also used to correct for unnoticed losses of urine. Both parameters, used in conjunction with blood lactate analysis, are suitable for a first screening of patients with enzymopathies of carbohydrate metabolism, and for the follow-up study of the steady or unsteady state of the patient with an enzyme defect of carbohydrate metabolism."} {"id": "PMID:174841", "title": "Corticosteroid sulfate excretion and estrogen receptors in breast cancer.", "content": "The urinary excretion of corticosteroid sulfates and free cortisol were determined in 150 breast cancer patients. Four of 60 cases of early breast cancer (7%) and 26 of 90 patients with advanced breast cancer (29%) showed an elevated urinary corticosteroid sulfate excretion. Urinary free cortisol was usually normal. Estrogen receptor assays were performed on tumor samples from 67 breast cancer patients; 24 were from primary lesions obtained at mastectomy, 3 from inoperable primaries in patients with systemic metastases, and 40 from metastases. Sixteen of the primary breast cancers (67%), 26 of the metastases (65%) and 1 of the 3 inoperable primaries contained estrogen receptors. With 2 exceptions, patients with an increased urinary corticosteroid sulfate excretion also had estrogen receptor-containing tumors.", "contents": "Corticosteroid sulfate excretion and estrogen receptors in breast cancer. The urinary excretion of corticosteroid sulfates and free cortisol were determined in 150 breast cancer patients. Four of 60 cases of early breast cancer (7%) and 26 of 90 patients with advanced breast cancer (29%) showed an elevated urinary corticosteroid sulfate excretion. Urinary free cortisol was usually normal. Estrogen receptor assays were performed on tumor samples from 67 breast cancer patients; 24 were from primary lesions obtained at mastectomy, 3 from inoperable primaries in patients with systemic metastases, and 40 from metastases. Sixteen of the primary breast cancers (67%), 26 of the metastases (65%) and 1 of the 3 inoperable primaries contained estrogen receptors. With 2 exceptions, patients with an increased urinary corticosteroid sulfate excretion also had estrogen receptor-containing tumors."} {"id": "PMID:174842", "title": "Male pseudohermaphroditism with hypertension due to a 17alpha-hydroxylation deficiency.", "content": "A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17alpha-hydroxylase deficiency demonstrated by low cortisol (0-56 mg/24 h), high corticosterone (270 mg/24 h) and 11-deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol(1-8 ng/dl) were all low. Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure.", "contents": "Male pseudohermaphroditism with hypertension due to a 17alpha-hydroxylation deficiency. A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17alpha-hydroxylase deficiency demonstrated by low cortisol (0-56 mg/24 h), high corticosterone (270 mg/24 h) and 11-deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol(1-8 ng/dl) were all low. Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure."} {"id": "PMID:174848", "title": "Ectodermal dysplasia, mental retardation, cleft lip/palate and other anomalies in three sibs.", "content": "Three females in a sibship of 10 have a syndrome of mental retardation, ectodermal dysplasia, and cleft lip and/or cleft palate. Inconstant features are congenital skin defects, areas of hyperpigmentation, congenital adhesions between the eyelids, cicatricial atrophy of the scalp, abnormal E.E.G., partial anodontia, genital hypoplasia, syndactyly, and delayed skeletal growth and maturation. The mode of inheritance could be either dominant with incomplete penetrance, or autosomal recessive. The disorder has overlapping features with several previously delineated syndromes but in view of certain novel features its relationship to these is uncertain.", "contents": "Ectodermal dysplasia, mental retardation, cleft lip/palate and other anomalies in three sibs. Three females in a sibship of 10 have a syndrome of mental retardation, ectodermal dysplasia, and cleft lip and/or cleft palate. Inconstant features are congenital skin defects, areas of hyperpigmentation, congenital adhesions between the eyelids, cicatricial atrophy of the scalp, abnormal E.E.G., partial anodontia, genital hypoplasia, syndactyly, and delayed skeletal growth and maturation. The mode of inheritance could be either dominant with incomplete penetrance, or autosomal recessive. The disorder has overlapping features with several previously delineated syndromes but in view of certain novel features its relationship to these is uncertain."} {"id": "PMID:174849", "title": "Triploidy syndrome. A report on two live-born (69, XXY) and one still-born (69, XXX) infants.", "content": "Two live-born cases, 69,XXY and one stillbirth, 69,XXX are reported. Further evidence is presented to delineate the triploidy syndrome. Common external and internal features which characterize the triploidy syndrome are low-set ears, hypertelorism, colobomata, syndactyly, simian creases, microphallus, undescended testes, scrotal aplasia, anomalous heart and hypoplasia of kidneys and adrenals. The triploidy syndrome encompasses features found in trisomies 13, 18 and 21. We suggest that the abnormal development of the triploidy infants is the result of the mentioned trisomies and their subsequent effect on the remaining genome.", "contents": "Triploidy syndrome. A report on two live-born (69, XXY) and one still-born (69, XXX) infants. Two live-born cases, 69,XXY and one stillbirth, 69,XXX are reported. Further evidence is presented to delineate the triploidy syndrome. Common external and internal features which characterize the triploidy syndrome are low-set ears, hypertelorism, colobomata, syndactyly, simian creases, microphallus, undescended testes, scrotal aplasia, anomalous heart and hypoplasia of kidneys and adrenals. The triploidy syndrome encompasses features found in trisomies 13, 18 and 21. We suggest that the abnormal development of the triploidy infants is the result of the mentioned trisomies and their subsequent effect on the remaining genome."} {"id": "PMID:174850", "title": "Inheritance of xanthomatosis and hyper-beta-lipoproteinaemia. A study of 7 large kindreds.", "content": "In a study of xanthomatosis in the county of Ostfold, Norway (approximately 220,000 inhabitants), it was found that 20% (37 out of 185) of the probands belonges to seven large kindreds where xanthomatosis and hyper-beta-lipoproteinaemia segregated. Almost complete ascertainment (99%) of living subjects in the sibships in these families was obtained. Within each kindred, the frequency distribution of age- and sex-adjusted cholesterol and LDL cholesterol were discontinuous; the xanthomatosis patients all had values corresponding to the upper mode, whereas no person without xanthomatosis had such values. The combined results showed a slight overlap. Triglyceride concentrations were unimodally distributed. The genetics of the disorder in the seven families was analysed on the basis of 270 individuals. The segregation pattern satisfied the criteria for autosomal dominant inheritance, but not those for a polygenic trait. Thus, xanthomatosis with hyper-beta-lipoproteinaemia segregates as an autosomal dominant trait in these seven kindreds. No evidence of reduced penetrance was found. Since both IIA and IIB lipoprotein patterns were observed within the same family, there is no evidence that the two patterns reflect the presence of different genes in these kindreds.", "contents": "Inheritance of xanthomatosis and hyper-beta-lipoproteinaemia. A study of 7 large kindreds. In a study of xanthomatosis in the county of Ostfold, Norway (approximately 220,000 inhabitants), it was found that 20% (37 out of 185) of the probands belonges to seven large kindreds where xanthomatosis and hyper-beta-lipoproteinaemia segregated. Almost complete ascertainment (99%) of living subjects in the sibships in these families was obtained. Within each kindred, the frequency distribution of age- and sex-adjusted cholesterol and LDL cholesterol were discontinuous; the xanthomatosis patients all had values corresponding to the upper mode, whereas no person without xanthomatosis had such values. The combined results showed a slight overlap. Triglyceride concentrations were unimodally distributed. The genetics of the disorder in the seven families was analysed on the basis of 270 individuals. The segregation pattern satisfied the criteria for autosomal dominant inheritance, but not those for a polygenic trait. Thus, xanthomatosis with hyper-beta-lipoproteinaemia segregates as an autosomal dominant trait in these seven kindreds. No evidence of reduced penetrance was found. Since both IIA and IIB lipoprotein patterns were observed within the same family, there is no evidence that the two patterns reflect the presence of different genes in these kindreds."} {"id": "PMID:174851", "title": "Further observations on familial hypobetaliproteinaemia.", "content": "A family with hypobetalipoproteinaemia with 10 affected members is described. In six patients low density lipoprotein cholesterol (LDL-c) concentrations were about 10 % of normal. In four LDL-c was reduced to about 50 % of normal; these four patients probably represent the \"intermediate\" form of hypobetalipoproteinaemia. This variation in total cholesterol concentration and LDL-c among the affected individuals of the same family could reflect differences of expression in a single aberrant gene or additive expression of a gene at a second locus.", "contents": "Further observations on familial hypobetaliproteinaemia. A family with hypobetalipoproteinaemia with 10 affected members is described. In six patients low density lipoprotein cholesterol (LDL-c) concentrations were about 10 % of normal. In four LDL-c was reduced to about 50 % of normal; these four patients probably represent the \"intermediate\" form of hypobetalipoproteinaemia. This variation in total cholesterol concentration and LDL-c among the affected individuals of the same family could reflect differences of expression in a single aberrant gene or additive expression of a gene at a second locus."} {"id": "PMID:174852", "title": "The inheritance of hyperlipoproteinaemia with xanthomatosis. A study of 132 kindreds.", "content": "In a study of xanthomatosis kindreds in the county of Ostfold, Norway, 95 % of the living first degree relatives of the probands were investigated. Hyperlipoproteinaemia (lipid values above the 95th percentile) was present in 40.8 % of 554 first degree relatives of probands with xanthomatosis. The distribution curve was bimodal for cholesterol and LDL cholesterol concentrations, but not for triglyceride concentration within the different categories of families. The IIA lipoprotein pattern was the most frequent lipoprotein abnormality, in probands as well as in affected first degree relatives. However, IIB and IV lipoprotein patterns were also found in affected family members, irrespective of the pattern in the probands. About 93% of the xanthomatosis subjects had a lipoprotein disorder segregating as an autosomal dominant; the remaining 7 % were sporadic cases and/or had a multifactorially determined xanthomatosis. More sibs that offspring were affected; this was particularly pronounced for males with a IIA lipoprotein pattern. The genetic analysis gave no reason to suspect that hypercholesterolaemia with a IIA pattern is not the same disease as hypercholesterolaemia with a IIB pattern. However, a significant number of xanthomatosis patients had more than one type of hyperlipoproteinaemia. The frequency of the xanthomatosis trait was estimated to be 3.2/1000, and the ascertainment probability 0.6. The prevalence of familial hypercholesterolaemia with xanthomatosis was estimated to be 2.2/1000 and the multiple type hyperlipoproteinaemia with xanthomatosis had a frequency of 1.0/1000.", "contents": "The inheritance of hyperlipoproteinaemia with xanthomatosis. A study of 132 kindreds. In a study of xanthomatosis kindreds in the county of Ostfold, Norway, 95 % of the living first degree relatives of the probands were investigated. Hyperlipoproteinaemia (lipid values above the 95th percentile) was present in 40.8 % of 554 first degree relatives of probands with xanthomatosis. The distribution curve was bimodal for cholesterol and LDL cholesterol concentrations, but not for triglyceride concentration within the different categories of families. The IIA lipoprotein pattern was the most frequent lipoprotein abnormality, in probands as well as in affected first degree relatives. However, IIB and IV lipoprotein patterns were also found in affected family members, irrespective of the pattern in the probands. About 93% of the xanthomatosis subjects had a lipoprotein disorder segregating as an autosomal dominant; the remaining 7 % were sporadic cases and/or had a multifactorially determined xanthomatosis. More sibs that offspring were affected; this was particularly pronounced for males with a IIA lipoprotein pattern. The genetic analysis gave no reason to suspect that hypercholesterolaemia with a IIA pattern is not the same disease as hypercholesterolaemia with a IIB pattern. However, a significant number of xanthomatosis patients had more than one type of hyperlipoproteinaemia. The frequency of the xanthomatosis trait was estimated to be 3.2/1000, and the ascertainment probability 0.6. The prevalence of familial hypercholesterolaemia with xanthomatosis was estimated to be 2.2/1000 and the multiple type hyperlipoproteinaemia with xanthomatosis had a frequency of 1.0/1000."} {"id": "PMID:174853", "title": "Immunological cross-reactivity between basic proteins of myelin and cancer. I. Lymphocyte transformation studies in immunized guinea-pigs.", "content": "The studies described were designed to examine the question of cross-reactivity between basic protein of myelin and a basic protein common to many human tumours. The lymphocytes from guinea-pigs injected with acid extracts of human cancer tissue showed significant (P less than 0-01) tranformation on exposure to basic protein of human myelin. Conversely lymphocytes from guinea-pigs injected with basic protein of human myelin showed significant (P less than 0-01) transformation on exposure to the acid extracts of human cancer tissue. Lymphocytes from control non-injected guinea-pigs did not transform on exposure to either antigen. These findings demonstrate immunological cross-reactivity in guinea-pigs between basic proteins of human myelin and of human cancer tissue using an assay system other than the macrophage electrophoretic migration hitherto used to show this effect in man.", "contents": "Immunological cross-reactivity between basic proteins of myelin and cancer. I. Lymphocyte transformation studies in immunized guinea-pigs. The studies described were designed to examine the question of cross-reactivity between basic protein of myelin and a basic protein common to many human tumours. The lymphocytes from guinea-pigs injected with acid extracts of human cancer tissue showed significant (P less than 0-01) tranformation on exposure to basic protein of human myelin. Conversely lymphocytes from guinea-pigs injected with basic protein of human myelin showed significant (P less than 0-01) transformation on exposure to the acid extracts of human cancer tissue. Lymphocytes from control non-injected guinea-pigs did not transform on exposure to either antigen. These findings demonstrate immunological cross-reactivity in guinea-pigs between basic proteins of human myelin and of human cancer tissue using an assay system other than the macrophage electrophoretic migration hitherto used to show this effect in man."} {"id": "PMID:174854", "title": "Smooth-muscle antibodies and other tissue antibodies in cytomegalovirus infection.", "content": "Smooth-muscle antibodies (SMA) were present in 16% of sixty-three patients with cytomegalovirus (CMV) antibodies in serum and absent in forty CMV antibody-negative blood donors (P = 0-005). The SMA were of the IgG and IgM class, while no IgA antibodies were found. In patients with CMV infection, SMA, mainly of the IgM class, were present in the early stages of the disease, and the titre decreased faster than the complement-fixing CMV antibody titre. Anti-nuclear antibodies (ANA) were also found more often in CMV antibody-positive sera than in CMV antibody-negative sera, and ANA were usually present in sera which also contained SMA. Parietal cell antibodies, mitochondrial antibodies and other cytoplasmic antibodies did not occur more frequently in CMV antibody-positive than in CMV antibody-negative sera.", "contents": "Smooth-muscle antibodies and other tissue antibodies in cytomegalovirus infection. Smooth-muscle antibodies (SMA) were present in 16% of sixty-three patients with cytomegalovirus (CMV) antibodies in serum and absent in forty CMV antibody-negative blood donors (P = 0-005). The SMA were of the IgG and IgM class, while no IgA antibodies were found. In patients with CMV infection, SMA, mainly of the IgM class, were present in the early stages of the disease, and the titre decreased faster than the complement-fixing CMV antibody titre. Anti-nuclear antibodies (ANA) were also found more often in CMV antibody-positive sera than in CMV antibody-negative sera, and ANA were usually present in sera which also contained SMA. Parietal cell antibodies, mitochondrial antibodies and other cytoplasmic antibodies did not occur more frequently in CMV antibody-positive than in CMV antibody-negative sera."} {"id": "PMID:174856", "title": "Viruses as teratogens.", "content": "There is nothing unique about rubella viruses or cytomegaloviruses. They are classic teratogens and, in this respect, not only follow but exemplify most of the principles of human teratology.", "contents": "Viruses as teratogens. There is nothing unique about rubella viruses or cytomegaloviruses. They are classic teratogens and, in this respect, not only follow but exemplify most of the principles of human teratology."} {"id": "PMID:174857", "title": "Endocrine assay in chorionic tumors.", "content": "Gestational chorionic tumors represent a rare biologic system for three reasons: They are a genetic mixture of both male and female; they are unusually responsive to chemotherapy with a high cure rate; and they always secrete hCG, which acts as a reliable cell marker with which to diagnose, to monitor drug therapy, and to follow-up to ensure continued remission. Nongestational chorionic tumors characteristically share only the latter unique attribute. For this reason, endocrine assays, particularly the measurement of hCG, play a vital role in the management of patients with these tumors. However, as the tools with which we work improve, and our understanding increases, it is quite likely that other tumors will be found to make substances that are similarly specific and reliable so as to be utilized in the same way. Already there are tests such as alpha-fetoprotein and carcinoembryonic antigen that are beginning to serve such a role but are not as specific as is hCG. Our experience with chorionic tumors has given us a valuable opportunity to develop techniques to be used for other tumor systems when reliable cell markers become available. When this time comes, we should be able to look forward to improved survival rates, hopefully approaching those obtained with chorionic disease.", "contents": "Endocrine assay in chorionic tumors. Gestational chorionic tumors represent a rare biologic system for three reasons: They are a genetic mixture of both male and female; they are unusually responsive to chemotherapy with a high cure rate; and they always secrete hCG, which acts as a reliable cell marker with which to diagnose, to monitor drug therapy, and to follow-up to ensure continued remission. Nongestational chorionic tumors characteristically share only the latter unique attribute. For this reason, endocrine assays, particularly the measurement of hCG, play a vital role in the management of patients with these tumors. However, as the tools with which we work improve, and our understanding increases, it is quite likely that other tumors will be found to make substances that are similarly specific and reliable so as to be utilized in the same way. Already there are tests such as alpha-fetoprotein and carcinoembryonic antigen that are beginning to serve such a role but are not as specific as is hCG. Our experience with chorionic tumors has given us a valuable opportunity to develop techniques to be used for other tumor systems when reliable cell markers become available. When this time comes, we should be able to look forward to improved survival rates, hopefully approaching those obtained with chorionic disease."} {"id": "PMID:174860", "title": "Syndactyly of upper limb. Morphogenesis, classification, and management.", "content": "The distinction between primary and secondary syndactyly is made on the basis of their relation to the morphogenesis. The latter is associated with antecedent malformation which results in subsequent refusion of parts. Based on these considerations, a practical classification is suggested. The management of the various types of malformations is considered in relation to the complexity of the structures involved. Certain deformities require very early treatment in order to permit prehensile function to the developing infant, or to release the impaired part. It is desirable to complete all surgery before the child enters school. The severe complex syndactyly could rarely be solved by one operation. Normal appearance and function are rarely attained and, with growth, newer problems of imbalance and contracture appear. While rehabilitation of the hand is seldom needed for the children with cutaneous syndactyly, the severe deformities associated with complex syndactyly often require supervision in order to regain the potential function and simple dynamic splints are very helpful.", "contents": "Syndactyly of upper limb. Morphogenesis, classification, and management. The distinction between primary and secondary syndactyly is made on the basis of their relation to the morphogenesis. The latter is associated with antecedent malformation which results in subsequent refusion of parts. Based on these considerations, a practical classification is suggested. The management of the various types of malformations is considered in relation to the complexity of the structures involved. Certain deformities require very early treatment in order to permit prehensile function to the developing infant, or to release the impaired part. It is desirable to complete all surgery before the child enters school. The severe complex syndactyly could rarely be solved by one operation. Normal appearance and function are rarely attained and, with growth, newer problems of imbalance and contracture appear. While rehabilitation of the hand is seldom needed for the children with cutaneous syndactyly, the severe deformities associated with complex syndactyly often require supervision in order to regain the potential function and simple dynamic splints are very helpful."} {"id": "PMID:174873", "title": "Mucus-secreting carcinoid tumor in a colonic diverticulum: report of a case.", "content": "A mucus-secreting carcinoid tumor arising in a colonic (rectosigmoid) diverticulum is presented. Carcinoid tumors in colonic diverticula have not been previously reported. The presence of mucin and argentaffin granules in the same tumor cell is illustrated. The recognition of mucus-secreting carcinoid tumors is emphasized in order to avoid overtreatment of small colonic carcinoid tumors by extensive surgical procedures.", "contents": "Mucus-secreting carcinoid tumor in a colonic diverticulum: report of a case. A mucus-secreting carcinoid tumor arising in a colonic (rectosigmoid) diverticulum is presented. Carcinoid tumors in colonic diverticula have not been previously reported. The presence of mucin and argentaffin granules in the same tumor cell is illustrated. The recognition of mucus-secreting carcinoid tumors is emphasized in order to avoid overtreatment of small colonic carcinoid tumors by extensive surgical procedures."} {"id": "PMID:174881", "title": "[Bactericidal dosie-activity relationships with E. coli, K. pneumoniae and Staph. aureus (author's transl)].", "content": "In investigations into the dosis-activity relationships of bactericidal antibiotics used against E. coli, K. pneumoniae and Staph. aureus four types of activity could be demonstrated. The penicillin type shows almost no improvement in bactericidal activity despite increasing the dosage above a certain level. An increase in concentration of aminoglycoside antibiotics led to a more rapid killing of the bacteria. In cefalotin there was a linear dosis-activity relationship: rising concentrations of antibiotics led to an ever increasing bactericidal effect. The paradoxical bactericidal effect (\"Eagle effect'') described for penicillin G with enterococci could not be demonstrated.", "contents": "[Bactericidal dosie-activity relationships with E. coli, K. pneumoniae and Staph. aureus (author's transl)]. In investigations into the dosis-activity relationships of bactericidal antibiotics used against E. coli, K. pneumoniae and Staph. aureus four types of activity could be demonstrated. The penicillin type shows almost no improvement in bactericidal activity despite increasing the dosage above a certain level. An increase in concentration of aminoglycoside antibiotics led to a more rapid killing of the bacteria. In cefalotin there was a linear dosis-activity relationship: rising concentrations of antibiotics led to an ever increasing bactericidal effect. The paradoxical bactericidal effect (\"Eagle effect'') described for penicillin G with enterococci could not be demonstrated."} {"id": "PMID:174885", "title": "Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors.", "content": "Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.", "contents": "Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors. Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action."} {"id": "PMID:174886", "title": "Hormonal regulation of renal ornithine decarboxylase activity in the rat.", "content": "The regulation of the activity of the renal enzyme ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) was examined in the rat. In the intact animal adapted to a light/dark cycle of 14 hours and 10 hours, respectively, the level of renal ornithine decarboxylase activity was rhythmical and paralleled the diurnal rhythm in plasma corticosteroid concentration. Renal ornithine decarboxylase activity and plasma corticosterone were highest during the early hours of darkness and lowest during the hours of light. Following hypophysectomy, the level of renal ornithine decarboxylase activity declined rapidly and remained low and without a demonstrable diurnal rhythm. When pituitary hormone levels were temporarily restored in the hypophysectomized rat by the injection of pituitary extract, renal ornithine decarboxylase activity increased rapidly, reached a peak within 8 hours, and returned toward pre-injection levels by 12 hours. Exogenous growth hormone, ACTH and cortisol each increased renal ornithine decarboxylase activity in the hypophysectomized rat, with the highest levels of activity being achieved with growth hormone. Other pituitary hormones (FSH, LH, TSH and prolactin) were ineffective. After bilateral adrenalectomy, renal ornithine decarboxylase activity retained a rhythmical pattern similar to that observed in the intact rat, but the levels were increased. Growth hormone and cortisol increased renal ornitine decarboxylase activity in the adrenalectomized-hypophysectomized animal to the same extent as in the hypophysectomized animal, but ACTH was almost totally ineffective. These data suggest that the pituitary plays a major role in the regulation of renal ornithine decarboxylase activity in the rat, primarily through the rhythmical secretion of growth hormone and ACTH.", "contents": "Hormonal regulation of renal ornithine decarboxylase activity in the rat. The regulation of the activity of the renal enzyme ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) was examined in the rat. In the intact animal adapted to a light/dark cycle of 14 hours and 10 hours, respectively, the level of renal ornithine decarboxylase activity was rhythmical and paralleled the diurnal rhythm in plasma corticosteroid concentration. Renal ornithine decarboxylase activity and plasma corticosterone were highest during the early hours of darkness and lowest during the hours of light. Following hypophysectomy, the level of renal ornithine decarboxylase activity declined rapidly and remained low and without a demonstrable diurnal rhythm. When pituitary hormone levels were temporarily restored in the hypophysectomized rat by the injection of pituitary extract, renal ornithine decarboxylase activity increased rapidly, reached a peak within 8 hours, and returned toward pre-injection levels by 12 hours. Exogenous growth hormone, ACTH and cortisol each increased renal ornithine decarboxylase activity in the hypophysectomized rat, with the highest levels of activity being achieved with growth hormone. Other pituitary hormones (FSH, LH, TSH and prolactin) were ineffective. After bilateral adrenalectomy, renal ornithine decarboxylase activity retained a rhythmical pattern similar to that observed in the intact rat, but the levels were increased. Growth hormone and cortisol increased renal ornitine decarboxylase activity in the adrenalectomized-hypophysectomized animal to the same extent as in the hypophysectomized animal, but ACTH was almost totally ineffective. These data suggest that the pituitary plays a major role in the regulation of renal ornithine decarboxylase activity in the rat, primarily through the rhythmical secretion of growth hormone and ACTH."} {"id": "PMID:174887", "title": "Actions of pregnant mare serum gonadotropin in the immature female rat: correlative changes in blood steroids, gonadotropins, and cytoplasmic estradiol receptors of the anterior pituitary and hypothalamus.", "content": "Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge resulting from PMSG administration to immature female rats. In addition, changes in blood steroids and gonadotropins after PMSG treatment are similar to those reported for proestrus-estrus-diestrus I of the normal adult estrous cycle. These findings further demonstrate the validity of the PMSG-primed immature female rat preparation as a model for the estrous cycle of the adult rat.", "contents": "Actions of pregnant mare serum gonadotropin in the immature female rat: correlative changes in blood steroids, gonadotropins, and cytoplasmic estradiol receptors of the anterior pituitary and hypothalamus. Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge resulting from PMSG administration to immature female rats. In addition, changes in blood steroids and gonadotropins after PMSG treatment are similar to those reported for proestrus-estrus-diestrus I of the normal adult estrous cycle. These findings further demonstrate the validity of the PMSG-primed immature female rat preparation as a model for the estrous cycle of the adult rat."} {"id": "PMID:174888", "title": "Binding of human chorionic gonadotropin and response of cyclic nucleotides to luteinizing hormone in luteal tissue from rats treated with prostaglandin F2alpha.", "content": "Prostaglandin F2alpha (PGF2alpha) caused a marked and highly reproducible fall of over 85% (P less than .001) in serum progesterone and in the capacity of luteal tissue to bind hCG, within 30 h. No change in the affinity of the receptor for iodinated hCG was observed. The addition of LH (1 mug/ml) to incubation flasks containing luteal tissue slices from both control and PGF2alpha-treated animals caused a significant stimulation of progesterone output in the control (P less than .05), but not in tissue previously exposed to PGF2alpha in vivo. Indeed, progesterone output by the latter tissue was severely reduced independent of the presence of LH. Although cAMP content was significantly elevated in luteal tissue incubated with LH (P less than .01), the degree of stimulation of cAMP by LH was reduced 35% (P less than .05) in luteal tissue from rats treated with PGF2alpha. The content of cGMP was generally reduced by addition of LH to the incubation media, by pretreatment of the animals with PGF2alpha, and by incubation alone. This study shows that luteolysis induced by PGF2alpha is accompanied by a loss in gonadotropin receptor, a conclusion supported by the loss in LH stimulation of cAMP and progesterone synthesis.", "contents": "Binding of human chorionic gonadotropin and response of cyclic nucleotides to luteinizing hormone in luteal tissue from rats treated with prostaglandin F2alpha. Prostaglandin F2alpha (PGF2alpha) caused a marked and highly reproducible fall of over 85% (P less than .001) in serum progesterone and in the capacity of luteal tissue to bind hCG, within 30 h. No change in the affinity of the receptor for iodinated hCG was observed. The addition of LH (1 mug/ml) to incubation flasks containing luteal tissue slices from both control and PGF2alpha-treated animals caused a significant stimulation of progesterone output in the control (P less than .05), but not in tissue previously exposed to PGF2alpha in vivo. Indeed, progesterone output by the latter tissue was severely reduced independent of the presence of LH. Although cAMP content was significantly elevated in luteal tissue incubated with LH (P less than .01), the degree of stimulation of cAMP by LH was reduced 35% (P less than .05) in luteal tissue from rats treated with PGF2alpha. The content of cGMP was generally reduced by addition of LH to the incubation media, by pretreatment of the animals with PGF2alpha, and by incubation alone. This study shows that luteolysis induced by PGF2alpha is accompanied by a loss in gonadotropin receptor, a conclusion supported by the loss in LH stimulation of cAMP and progesterone synthesis."} {"id": "PMID:174889", "title": "Immunoreactive alpha-MSH and ACTH levels in rat plasma and pituitary.", "content": "A radioimmunoassay is described for the measurement of alpha-melanocyte-stimulating hormone (alpha-MSH). The antibody was produced in rabbits by immunization with alpha-MSH coupled to bovine serum albumin with carbodiimide. The antibody did not react significantly with ACTH, beta-MSH, or 6 fragments of ACTH. The sensitivity and reliability of the assay were improved by employing a simple plasma extraction procedure. When applied to a 2 ml plasma sample, the detection limit of the radioimmunoassay was 6 pg/ml. ACTH was measured with a sensitive and specific radioimmunoassay previously described for humans and adapted for the rat. The anti-ACTH serum cross-reacted with the biologically active portion of alpha-p ACTH and not with alpha-MSH, beta-MSH or the alpha-p 17-39 and alpha-p 25-39 fragments of ACTH. The detection limit was 20 pg/ml. Plasma and pituitary alpha-MSH and ACTH had the same immunoreactivity as synthetic alpha-MSH and ACTH. alpha-MSH and ACTH contents of the rat neurointermediate lobe were 1398 +/- 360 (SE) ng and 28.2 +/- 2.9 ng, respectively, while in the anterior lobe they were 102 +/- 31 ng and 551 +/- 36 ng, respectively. The plasma alpha-MSH concentration at 8 AM in male rats was 64 +/- 8 pg/ml when the plasma ACTH concentration was 92 +/- 15 pg/ml. Over a 24-hour period two peaks of plasma alpha-MSH were observed, one at 4 AM (142 +/- 35 pg/ml) and the other at 4 PM (139 +/- 26 pg/ml). Plasma ACTH was higher at noon (151 +/- 43 pg/ml) and 4 PM (130 +/- 48 pg/ml). Short-term exposure to ether induced a transient increase in alpha-MSH level 5 min later and a rapid return to normal levels. Plasma ACTH increased significantly 2.5 min after the onset of ether stress and remained high for 30 min. Two hours' exposure to ether did not change plasma alpha-MSH, although a 3-fold increase in plasma ACTH was observed. Haloperidol injection was followed by a large increase in plasma alpha-MSH, whereas ACTH levels increased similarly after saline and Haloperidol injection. Corticoid administration reduced ACTH, but not alpha-MSH. Three weeks after adrenalectomy, alpha-MSH levels had not changed but ACTH levels had increased ten-fold. These data indicate that alpha-MSH is secreted in the rat, and that the regulation of its secretion is different from that of ACTH.", "contents": "Immunoreactive alpha-MSH and ACTH levels in rat plasma and pituitary. A radioimmunoassay is described for the measurement of alpha-melanocyte-stimulating hormone (alpha-MSH). The antibody was produced in rabbits by immunization with alpha-MSH coupled to bovine serum albumin with carbodiimide. The antibody did not react significantly with ACTH, beta-MSH, or 6 fragments of ACTH. The sensitivity and reliability of the assay were improved by employing a simple plasma extraction procedure. When applied to a 2 ml plasma sample, the detection limit of the radioimmunoassay was 6 pg/ml. ACTH was measured with a sensitive and specific radioimmunoassay previously described for humans and adapted for the rat. The anti-ACTH serum cross-reacted with the biologically active portion of alpha-p ACTH and not with alpha-MSH, beta-MSH or the alpha-p 17-39 and alpha-p 25-39 fragments of ACTH. The detection limit was 20 pg/ml. Plasma and pituitary alpha-MSH and ACTH had the same immunoreactivity as synthetic alpha-MSH and ACTH. alpha-MSH and ACTH contents of the rat neurointermediate lobe were 1398 +/- 360 (SE) ng and 28.2 +/- 2.9 ng, respectively, while in the anterior lobe they were 102 +/- 31 ng and 551 +/- 36 ng, respectively. The plasma alpha-MSH concentration at 8 AM in male rats was 64 +/- 8 pg/ml when the plasma ACTH concentration was 92 +/- 15 pg/ml. Over a 24-hour period two peaks of plasma alpha-MSH were observed, one at 4 AM (142 +/- 35 pg/ml) and the other at 4 PM (139 +/- 26 pg/ml). Plasma ACTH was higher at noon (151 +/- 43 pg/ml) and 4 PM (130 +/- 48 pg/ml). Short-term exposure to ether induced a transient increase in alpha-MSH level 5 min later and a rapid return to normal levels. Plasma ACTH increased significantly 2.5 min after the onset of ether stress and remained high for 30 min. Two hours' exposure to ether did not change plasma alpha-MSH, although a 3-fold increase in plasma ACTH was observed. Haloperidol injection was followed by a large increase in plasma alpha-MSH, whereas ACTH levels increased similarly after saline and Haloperidol injection. Corticoid administration reduced ACTH, but not alpha-MSH. Three weeks after adrenalectomy, alpha-MSH levels had not changed but ACTH levels had increased ten-fold. These data indicate that alpha-MSH is secreted in the rat, and that the regulation of its secretion is different from that of ACTH."} {"id": "PMID:174890", "title": "Effects of pinealectomy on adrenal function in vivo and in vitro in female rats.", "content": "Female rats were ovariectomized and either sham-pinealectomized or pinealectomized on day 24 of age and exposed to a photoperiod of 12 h light: 12 h dark. In vivo and in vitro measures of adrenocortical function were made at 6, 7, and 8 weeks of age (18, 25, and 32 days post-pinealectomy, respectively). Pinealectomy diminished the post-castration rise in adrenal 5alpha-reductase activity in all age groups (P less than .05). The proportionate secretion of corticosterone (compared with the total steroid output) by adrenal slices was likewise enhanced (P less than .05) although the secretion and production of corticosterone in vitro was not altered. Pinealectomy substantially diminished (P less than .05) the in vivo secretion rates of reduced metabolites of corticosterone (dihydrocorticosterone and tetrahydrocorticosterone) without altering corticosterone secretion. Consequently, proportionate secretion of corticosterone in vivo was also enhanced (P less than .05). These findings are consistent with the notion that in ovariectomized rats removal of the pineal gland diminishes adrenal 5alpha-reductase activity without affecting ACTH secretion. However, in rats with ovaries intact, estrogen modified the effects of pinealectomy. Not only was the intra-adrenal metabolism of corticosterone diminished (higher proportionate output), but also resting levels of plasma corticosterone (P less than .01), corticosterone production in vitro (P less than .05), and total adrenal steroidogenesis in vitro (P less than .01) were increased. Thus, ACTH secretion may be enhanced following pineal removal in the presence of estrogen. The data suggest that the pineal gland, together with the ovaries, plays a role in the modulation of adrenal steroidogenesis.", "contents": "Effects of pinealectomy on adrenal function in vivo and in vitro in female rats. Female rats were ovariectomized and either sham-pinealectomized or pinealectomized on day 24 of age and exposed to a photoperiod of 12 h light: 12 h dark. In vivo and in vitro measures of adrenocortical function were made at 6, 7, and 8 weeks of age (18, 25, and 32 days post-pinealectomy, respectively). Pinealectomy diminished the post-castration rise in adrenal 5alpha-reductase activity in all age groups (P less than .05). The proportionate secretion of corticosterone (compared with the total steroid output) by adrenal slices was likewise enhanced (P less than .05) although the secretion and production of corticosterone in vitro was not altered. Pinealectomy substantially diminished (P less than .05) the in vivo secretion rates of reduced metabolites of corticosterone (dihydrocorticosterone and tetrahydrocorticosterone) without altering corticosterone secretion. Consequently, proportionate secretion of corticosterone in vivo was also enhanced (P less than .05). These findings are consistent with the notion that in ovariectomized rats removal of the pineal gland diminishes adrenal 5alpha-reductase activity without affecting ACTH secretion. However, in rats with ovaries intact, estrogen modified the effects of pinealectomy. Not only was the intra-adrenal metabolism of corticosterone diminished (higher proportionate output), but also resting levels of plasma corticosterone (P less than .01), corticosterone production in vitro (P less than .05), and total adrenal steroidogenesis in vitro (P less than .01) were increased. Thus, ACTH secretion may be enhanced following pineal removal in the presence of estrogen. The data suggest that the pineal gland, together with the ovaries, plays a role in the modulation of adrenal steroidogenesis."} {"id": "PMID:174891", "title": "Temporal relationships between hormone receptor binding and biological responses in the uterus: studies with short- and long-acting derivatives of estriol.", "content": "The temporal relationships between hormone receptor binding and early and late biological responses in the uterus were examined using estriol (E3), a weak estrogen, and several more long-acting estriol derivatives, namely ethinyl estriol (EE3), estriol cyclopentyl ether (E3CPE), and ethinyl estriol cyclopentyl ether (EE3CPE). Dose-response curves of 3-day uterotrophic assays indicate that biological potency follows the order EE3CPE greater than EE3 or estradiol greater than E3CPE greater than E3. After a single injection of 5 mug of compound, E3 elicits the early uterotrophic responses (increased uterine wet weight and 2-deoxyglucose phosphorylation at 2-6 h) but gives only weak stimulation of later uterotrophic responses (enhanced rates of 2-deoxyglucose phosphorylation at 20-24 h and increased DNA synthesis rate and uterine weight over a 72 h period). E3, EE3, and estradiol all elicit a rapid (maximal by 1/2-1 h) uptake of receptor into the nucleus and show an equivalent wet weight response at 3 h. After E3, nuclear receptor levels and uterine weight decline rapidly; however, after EE3 or estradiol, nuclear receptor levels decline less rapidly remaining at least two-fold above the control until 24-48 hr, and uterine weight also remains elevated for at least 48-72 h. EE3CPE elicits both the early (4 h) and later (20-24 h) waves of glucose metabolism, shows a prolonged effect on DNA synthesis rate, and shows the most dramatic and prolonged (beyond 72 h) maintenance of elevated uterine weight and high nuclear receptor (beyond 24 h). Thus, chemical modifications of the estriol molecule which result in a prolonged stimulation of uterine growth and metabolism also result in a long-term maintenance of hormone-receptor complex in the uterine nucleus. These studies give strong support to the concept that true uterine growth requires the direct and prolonged influence of the nuclear estrogen-receptor complex.", "contents": "Temporal relationships between hormone receptor binding and biological responses in the uterus: studies with short- and long-acting derivatives of estriol. The temporal relationships between hormone receptor binding and early and late biological responses in the uterus were examined using estriol (E3), a weak estrogen, and several more long-acting estriol derivatives, namely ethinyl estriol (EE3), estriol cyclopentyl ether (E3CPE), and ethinyl estriol cyclopentyl ether (EE3CPE). Dose-response curves of 3-day uterotrophic assays indicate that biological potency follows the order EE3CPE greater than EE3 or estradiol greater than E3CPE greater than E3. After a single injection of 5 mug of compound, E3 elicits the early uterotrophic responses (increased uterine wet weight and 2-deoxyglucose phosphorylation at 2-6 h) but gives only weak stimulation of later uterotrophic responses (enhanced rates of 2-deoxyglucose phosphorylation at 20-24 h and increased DNA synthesis rate and uterine weight over a 72 h period). E3, EE3, and estradiol all elicit a rapid (maximal by 1/2-1 h) uptake of receptor into the nucleus and show an equivalent wet weight response at 3 h. After E3, nuclear receptor levels and uterine weight decline rapidly; however, after EE3 or estradiol, nuclear receptor levels decline less rapidly remaining at least two-fold above the control until 24-48 hr, and uterine weight also remains elevated for at least 48-72 h. EE3CPE elicits both the early (4 h) and later (20-24 h) waves of glucose metabolism, shows a prolonged effect on DNA synthesis rate, and shows the most dramatic and prolonged (beyond 72 h) maintenance of elevated uterine weight and high nuclear receptor (beyond 24 h). Thus, chemical modifications of the estriol molecule which result in a prolonged stimulation of uterine growth and metabolism also result in a long-term maintenance of hormone-receptor complex in the uterine nucleus. These studies give strong support to the concept that true uterine growth requires the direct and prolonged influence of the nuclear estrogen-receptor complex."} {"id": "PMID:174892", "title": "Characterization of an inhibitor for luteinizing hormone receptor site binding.", "content": "An inhibitor for luteinizing hormone (LH) receptor site binding has been partially purified from aqueous extracts of ovaries from pseudo-pregnant or pregnant rats. The LH receptor binding inhibitor (LH-RBI) was heat-resistant, partially inactivated by trypsin or pronase digestion, and had a molecular weight of approximately 3800 daltons. The LH-RBI was not found in the ovary of mature non-pregnant rats or immature rats, nor was it found in testis or liver extracts. The LH-RBI strongly inhibited the in vitro binding of 125I-labeled ovine LH to ovarian LH receptors but did not inhibit 125I-labeled ovine prolactin binding to ovarian PRL receptors.", "contents": "Characterization of an inhibitor for luteinizing hormone receptor site binding. An inhibitor for luteinizing hormone (LH) receptor site binding has been partially purified from aqueous extracts of ovaries from pseudo-pregnant or pregnant rats. The LH receptor binding inhibitor (LH-RBI) was heat-resistant, partially inactivated by trypsin or pronase digestion, and had a molecular weight of approximately 3800 daltons. The LH-RBI was not found in the ovary of mature non-pregnant rats or immature rats, nor was it found in testis or liver extracts. The LH-RBI strongly inhibited the in vitro binding of 125I-labeled ovine LH to ovarian LH receptors but did not inhibit 125I-labeled ovine prolactin binding to ovarian PRL receptors."} {"id": "PMID:174893", "title": "Hormonal responsiveness of adenylate cyclase activity in cartilage.", "content": "Adenylate cyclase activity was measured in a crude particulate fraction of hyaline cartilage obtained from the xiphoid process of the rat. Bovine parathyroid hormone (PTH) at concentrations as low as 1.3 x 10(-7)M and porcine calcitonin (CT) at concentrations as low as 2.3 x 10(-5)M significantly increased adenylate cyclase activity. Glucagon, prostaglandin E1 (PGE1) and E2 (PG2), and epinephrine at concentrations of 10(-5)M also increased activity, whereas, no increased activity was seen with the additions of somatotrophin (10 mug/ml), PGF1alpha, PGF2alpha, or T3 at 10(-5)M. The combination of doses of PTH and CT, which individually produced maximal responses, was not additive. These data provide evidence that cartilage in growing rats responds directly to PTH and CT.", "contents": "Hormonal responsiveness of adenylate cyclase activity in cartilage. Adenylate cyclase activity was measured in a crude particulate fraction of hyaline cartilage obtained from the xiphoid process of the rat. Bovine parathyroid hormone (PTH) at concentrations as low as 1.3 x 10(-7)M and porcine calcitonin (CT) at concentrations as low as 2.3 x 10(-5)M significantly increased adenylate cyclase activity. Glucagon, prostaglandin E1 (PGE1) and E2 (PG2), and epinephrine at concentrations of 10(-5)M also increased activity, whereas, no increased activity was seen with the additions of somatotrophin (10 mug/ml), PGF1alpha, PGF2alpha, or T3 at 10(-5)M. The combination of doses of PTH and CT, which individually produced maximal responses, was not additive. These data provide evidence that cartilage in growing rats responds directly to PTH and CT."} {"id": "PMID:174894", "title": "Steroid formation and differentiation of cortical cells in tissue culture of human fetal adrenals in the presence and absence of ACTH.", "content": "Steroid secretion and ultrastructural differentiation of human fetal adrenal cortical cells were analyzed in tissue culture with and without ACTH. The unconjugated and sulfated endogenous neutral steroids were analyzed by gas-liquid chromatography and gas chromatography-mass spectrometry. A fetal pattern of neutral steroids, including high concentrations of sulfate conjugates, was found during the first five days of the cultivation. At 6 to 11 days of cultivation, a decrease was seen in concentrations of these steroids. However, when stimulated with ACTH, an increasing amount of steroids was secreted during days 6 to 11 and their pattern was transformed into the adult type with a 30-200 times higher secretion rate of cortisol. Cortical cells capable of proliferation in the culture had the ultrastructure of the permanent zone cells of the fetal adrenal or adult zona glomerulosa type. ACTH stimulation induced a differentiation of these cells into zona fasciculata type. The results suggest that ACTH is the main hormonal regulator in the genesis of the adult human adrenal cortex and that there is a factor during fetal life which inhibits the synthesis of the 3beta-hydroxysteroid dehydrogenase system.", "contents": "Steroid formation and differentiation of cortical cells in tissue culture of human fetal adrenals in the presence and absence of ACTH. Steroid secretion and ultrastructural differentiation of human fetal adrenal cortical cells were analyzed in tissue culture with and without ACTH. The unconjugated and sulfated endogenous neutral steroids were analyzed by gas-liquid chromatography and gas chromatography-mass spectrometry. A fetal pattern of neutral steroids, including high concentrations of sulfate conjugates, was found during the first five days of the cultivation. At 6 to 11 days of cultivation, a decrease was seen in concentrations of these steroids. However, when stimulated with ACTH, an increasing amount of steroids was secreted during days 6 to 11 and their pattern was transformed into the adult type with a 30-200 times higher secretion rate of cortisol. Cortical cells capable of proliferation in the culture had the ultrastructure of the permanent zone cells of the fetal adrenal or adult zona glomerulosa type. ACTH stimulation induced a differentiation of these cells into zona fasciculata type. The results suggest that ACTH is the main hormonal regulator in the genesis of the adult human adrenal cortex and that there is a factor during fetal life which inhibits the synthesis of the 3beta-hydroxysteroid dehydrogenase system."} {"id": "PMID:174895", "title": "A specific FSH receptor in rat granulosa cells: properties of binding in vitro.", "content": "The specific binding of [125I]iodoFSH to granulosa cells collected from immature, hypophysectomized, DES-treated rats, was studied in vitro. Specific binding occurred after 5 min and reached maximum after 3 h of incubation at 37 C. Non specific binding was very low (less than 10% of the total binding). The [25I]iodoFSH remained tightly associated with the receptor at pH 7.5, but was rapidly dissociated at pH 5. Unlabeled hFSH competitively inhibited [125I]iodoFSH binding. Kinetic analyses of equilibrium binding experiments gave an apparent association constant (Ka) of 1.34 (+/- 0.31) x 10(10)M-1 [mean (+/- SE)] and a number of binding sites per cell of (NB) 1, 130 +/- 70 (mean +/- SE). Rat prolactin, wheat germ agglutinin, and concanavalin-A did not compete with [125I]iodoFSH, but hLH, hCG, and rTSH competed at doses 300- to 900-fold higher than those of hFSH. Granulosa cells isolated from adult DES-treated rats, as well as cells collected from medium and preovulatory follicles of proestrous rats, gave Ka and NB values similar to those described above. A comparative study of rabbit granulosa cells indicated a much lower binding affinity compared with those from the rat.", "contents": "A specific FSH receptor in rat granulosa cells: properties of binding in vitro. The specific binding of [125I]iodoFSH to granulosa cells collected from immature, hypophysectomized, DES-treated rats, was studied in vitro. Specific binding occurred after 5 min and reached maximum after 3 h of incubation at 37 C. Non specific binding was very low (less than 10% of the total binding). The [25I]iodoFSH remained tightly associated with the receptor at pH 7.5, but was rapidly dissociated at pH 5. Unlabeled hFSH competitively inhibited [125I]iodoFSH binding. Kinetic analyses of equilibrium binding experiments gave an apparent association constant (Ka) of 1.34 (+/- 0.31) x 10(10)M-1 [mean (+/- SE)] and a number of binding sites per cell of (NB) 1, 130 +/- 70 (mean +/- SE). Rat prolactin, wheat germ agglutinin, and concanavalin-A did not compete with [125I]iodoFSH, but hLH, hCG, and rTSH competed at doses 300- to 900-fold higher than those of hFSH. Granulosa cells isolated from adult DES-treated rats, as well as cells collected from medium and preovulatory follicles of proestrous rats, gave Ka and NB values similar to those described above. A comparative study of rabbit granulosa cells indicated a much lower binding affinity compared with those from the rat."} {"id": "PMID:174896", "title": "Effects of hyperosmolarity on the cyclic AMP concentration and lipolysis of the adipocyte stimulated by adrenocorticotropic hormone.", "content": "The effects of ACTH on 3',5'-cyclic AMP (cAMP) levels and lipolysis were examined on isolated adipocytes incubated in either isosmolar or hyperosmolar media. The ability of ACTH to induce intracellular cAMP accumulation was greatly enhanced by incubating cells in hyperosmolar sucrose (100 to 400 mM) solutions. Hyperosmolar solutions prepared by the addition of either NaCL, glucose or mannitol enhanced the ACTH effect on cAMP to the same extent as did the hyperosmolar sucrose solution, but hyperosmolar urea solutions did not have such an effect. The effect of hyperosmolarity was shown only in cells stimulated by lipolytic hormones, and the effects were still evident in the presence of high concentrations of theophylline, indicating the effect of hyperosmolarity is to facilitate hormone action on the receptor-coupler system of the adipocyte membrane. The action of glucagon on cAMP was augmented much less than the actions of ACTH and isoproterenol. Basal as well as ACTH or exogenous cAMP stimulated lipolysis was lower in hyperosmolar sucrose solutions. Some mechanism by which hyperosmolarity interferes with the metabolic sequence beyond the accumulation of cAMP was suggested.", "contents": "Effects of hyperosmolarity on the cyclic AMP concentration and lipolysis of the adipocyte stimulated by adrenocorticotropic hormone. The effects of ACTH on 3',5'-cyclic AMP (cAMP) levels and lipolysis were examined on isolated adipocytes incubated in either isosmolar or hyperosmolar media. The ability of ACTH to induce intracellular cAMP accumulation was greatly enhanced by incubating cells in hyperosmolar sucrose (100 to 400 mM) solutions. Hyperosmolar solutions prepared by the addition of either NaCL, glucose or mannitol enhanced the ACTH effect on cAMP to the same extent as did the hyperosmolar sucrose solution, but hyperosmolar urea solutions did not have such an effect. The effect of hyperosmolarity was shown only in cells stimulated by lipolytic hormones, and the effects were still evident in the presence of high concentrations of theophylline, indicating the effect of hyperosmolarity is to facilitate hormone action on the receptor-coupler system of the adipocyte membrane. The action of glucagon on cAMP was augmented much less than the actions of ACTH and isoproterenol. Basal as well as ACTH or exogenous cAMP stimulated lipolysis was lower in hyperosmolar sucrose solutions. Some mechanism by which hyperosmolarity interferes with the metabolic sequence beyond the accumulation of cAMP was suggested."} {"id": "PMID:174897", "title": "Enzymatic dissociation and short-term culture of isolated rat anterior pituitary cells for studies on the control of hormone secretion.", "content": "A convenient procedure has been developed for preparing a suspension of isolated rat anterior pituitary cells which retains responsiveness to secretagogues. Rat anterior pituitaries were dispersed with collagenase and hyaluronidase followed by mechanical dispersion by means of a Pasteur pipette. Immediately after dispersion, the cells showed only slight responses to secretagogues, whereas after short-term culture (20-22 h) in the presence of sera, the cells recovered their ability to respond to synthetic LH-releasing hormone (LHRH) and synthetic thyrotropin-releasing hormone (TRH). During a 3-h incubation, cells prepared from pituitaries of male rats released LH and FSH, or TSH and prolactin (PRL) in amounts directly related to the dose of synthetic LHRH or TRH, respectively. The minimum effective concentrations of hypophysiotropic hormones lay between 10(-10) and 10(-9)M, although it was observed that cells originating from female rats usually gave quicker and larger responses to LHRH. No significant net increase in the total hormonal content (cells + medium) of radioimmunoassayable LH or FSH in response to LHRH, or of TSH or PRL in response to TRH, was observed during the 3-h incubation period. The cells released significant amounts of PRL, TSH, and to a lesser extent, LH, in response to 1-5 X 10-3M N6,O2'-dibutyryl cyclic AMP, accompanied by remarkable elevation in total content (cells + medium) of PRL and TSH but not of LH. The response of the cells to theophylline or high [K+] was similar to that usually observed in previous hemipituitary experiments. These results demonstrate the viability of this in vitro cell system and its suitability for further study of the regulation of the secretion of pituitary hormones.", "contents": "Enzymatic dissociation and short-term culture of isolated rat anterior pituitary cells for studies on the control of hormone secretion. A convenient procedure has been developed for preparing a suspension of isolated rat anterior pituitary cells which retains responsiveness to secretagogues. Rat anterior pituitaries were dispersed with collagenase and hyaluronidase followed by mechanical dispersion by means of a Pasteur pipette. Immediately after dispersion, the cells showed only slight responses to secretagogues, whereas after short-term culture (20-22 h) in the presence of sera, the cells recovered their ability to respond to synthetic LH-releasing hormone (LHRH) and synthetic thyrotropin-releasing hormone (TRH). During a 3-h incubation, cells prepared from pituitaries of male rats released LH and FSH, or TSH and prolactin (PRL) in amounts directly related to the dose of synthetic LHRH or TRH, respectively. The minimum effective concentrations of hypophysiotropic hormones lay between 10(-10) and 10(-9)M, although it was observed that cells originating from female rats usually gave quicker and larger responses to LHRH. No significant net increase in the total hormonal content (cells + medium) of radioimmunoassayable LH or FSH in response to LHRH, or of TSH or PRL in response to TRH, was observed during the 3-h incubation period. The cells released significant amounts of PRL, TSH, and to a lesser extent, LH, in response to 1-5 X 10-3M N6,O2'-dibutyryl cyclic AMP, accompanied by remarkable elevation in total content (cells + medium) of PRL and TSH but not of LH. The response of the cells to theophylline or high [K+] was similar to that usually observed in previous hemipituitary experiments. These results demonstrate the viability of this in vitro cell system and its suitability for further study of the regulation of the secretion of pituitary hormones."} {"id": "PMID:174898", "title": "Biochemical actions of follice-stimulating hormone in the sertoli cell of the rat testis.", "content": "The sequenc of biochemical events associated with the action of follicle-stimulating hormone (FSH) in the testis has been investigated using a Sertoli cell-enriched testis model system. The Sertoli cell-encriched testis, created by irradiation of male rats in utero, is devoid of germinal elements but contains a normal complement of supportive Sertoli cells. Comparison of the Sertoli cell-enriched testis with normal testis, demonstrates that the two types of testes contain equal numbers of FSH specific receptors, judged by the binding of labeled hormone. In addition, FSH over a concentration range from 6 X 10(-11) to 6 X 10(-9)M will stimulate the production of adenosine 3',5' monophosphate (cAMP) in the Sertoli cell-enriched testis in a manner indistinguishable from that of the normal testis. Incubation of Sertoli cell enriched testis also results in the activation of soluble cAMP-dependent protein kinase. This response to FSH is dependent upon the age of the animal and disappears at about 32 days of age. While sensitivity to the hormone can still be detected in mature Sertoli cell-enriched animals by the addition of the phosphodiesterase inhibitor 1-methyl-3-isobutyl-xanthine, no detectable increase in phosphodiesterase activity is apparent after 30 days of age. Injection of FSH into Sertoli cell-enriched animals results in an increase in total testicular protein synthesis as well as in the production of the Sertoli cell-specific protein, androgen-binding protein within 30 minutes. Furthermore, while hypophysectomy of Sertoli cell-enriched animals result in a decline of the testicular concentration of androgen-binding protein, the injection of FSH will stimulate and maintain the levels of androgen-binding protein in such animals. These results demonstrate that the Sertoli cell-enriched testis is capable of carrying out the sequence of biochemical events previously described for FSH in the normal testis and therefore, suggest that the Sertoli cell is the primary target cell for FSH action.", "contents": "Biochemical actions of follice-stimulating hormone in the sertoli cell of the rat testis. The sequenc of biochemical events associated with the action of follicle-stimulating hormone (FSH) in the testis has been investigated using a Sertoli cell-enriched testis model system. The Sertoli cell-encriched testis, created by irradiation of male rats in utero, is devoid of germinal elements but contains a normal complement of supportive Sertoli cells. Comparison of the Sertoli cell-enriched testis with normal testis, demonstrates that the two types of testes contain equal numbers of FSH specific receptors, judged by the binding of labeled hormone. In addition, FSH over a concentration range from 6 X 10(-11) to 6 X 10(-9)M will stimulate the production of adenosine 3',5' monophosphate (cAMP) in the Sertoli cell-enriched testis in a manner indistinguishable from that of the normal testis. Incubation of Sertoli cell enriched testis also results in the activation of soluble cAMP-dependent protein kinase. This response to FSH is dependent upon the age of the animal and disappears at about 32 days of age. While sensitivity to the hormone can still be detected in mature Sertoli cell-enriched animals by the addition of the phosphodiesterase inhibitor 1-methyl-3-isobutyl-xanthine, no detectable increase in phosphodiesterase activity is apparent after 30 days of age. Injection of FSH into Sertoli cell-enriched animals results in an increase in total testicular protein synthesis as well as in the production of the Sertoli cell-specific protein, androgen-binding protein within 30 minutes. Furthermore, while hypophysectomy of Sertoli cell-enriched animals result in a decline of the testicular concentration of androgen-binding protein, the injection of FSH will stimulate and maintain the levels of androgen-binding protein in such animals. These results demonstrate that the Sertoli cell-enriched testis is capable of carrying out the sequence of biochemical events previously described for FSH in the normal testis and therefore, suggest that the Sertoli cell is the primary target cell for FSH action."} {"id": "PMID:174899", "title": "Control of uterine estrogen receptor levels by progesterone.", "content": "The mechanism by which progesterone antagonizes estrogenic stimulation of uterine growth was examined in the immature rat. Rats received daily injections of 2.5 mug estradiol (E) for 2 days and on day 3 either 2.5 mug E or 2.5 mug E plus 2.5 mg of progesterone (P). The quantity of nuclear and cytoplasmic estrogen receptor was determined by [3H]estradiol exchange at various intervals after injection of E or E + P. In both groups, nuclear receptor estrogen complex (RnE) increased dramtically one hour after injection and showed a gradual decline from 4 to 24 h after injection. The quantity of cytoplasmic receptor, Rc, decreased to low levels by one hour and began a gradual increase from 4 to 8 h in both groups. However, between 8 and 24 h after injection, the level of Rc continued to increase in the E treatment group (2.39 +/- 0.21 pmol/uterus at 24 h) but remained at the 8 h level in the E + P group (1.09 +/- 0.04 pmol/uterus at 24 h). This observation suggests that two seperate processes are involved in the replenishment of Rc and that progesterone inhibits the second phase of replenishment. The binding affinity and specificity of Rc for estrogens following E + P pretreatment were identical to those of the E pretreatment group. Therefore, P does not alter the binding properties but rather the intrauterine level of Rc. Treatment with E on day 4, when Rc levels differ between E and E + P groups, stimulated uterine weight and protein content on day 5 in the E pretreatment group. However, minimal stimulation was observed in the E + P pretreatment group. The quantity of RnE and the time of nuclear retention of RnE following E injection on day 4 was greater in the E group than in the E + P group. The effect of progesterone on Rc replenishment was dose-dependent (range, 0.1-2.5 mg; 1/2 maximal, 0.5 mg). Injection of testosterone propionate (1.0 mg), a weak estrogen antagonist, with E on day 3 resulted in slightly reduced levels of Rc on day 4. This reduction also correlated with a reduced sensitivity to treatment with E on day 4. These data, together with previous studies from our laboratory, suggest that progesterone and other estrogen antagonists such as nafoxidine and testosterone propionate inhibit estrogen action by interfering with the replenishment of Rc, thereby reducing the number of receptor estrogen complexes that are translocated and retained by uterine nuclei.", "contents": "Control of uterine estrogen receptor levels by progesterone. The mechanism by which progesterone antagonizes estrogenic stimulation of uterine growth was examined in the immature rat. Rats received daily injections of 2.5 mug estradiol (E) for 2 days and on day 3 either 2.5 mug E or 2.5 mug E plus 2.5 mg of progesterone (P). The quantity of nuclear and cytoplasmic estrogen receptor was determined by [3H]estradiol exchange at various intervals after injection of E or E + P. In both groups, nuclear receptor estrogen complex (RnE) increased dramtically one hour after injection and showed a gradual decline from 4 to 24 h after injection. The quantity of cytoplasmic receptor, Rc, decreased to low levels by one hour and began a gradual increase from 4 to 8 h in both groups. However, between 8 and 24 h after injection, the level of Rc continued to increase in the E treatment group (2.39 +/- 0.21 pmol/uterus at 24 h) but remained at the 8 h level in the E + P group (1.09 +/- 0.04 pmol/uterus at 24 h). This observation suggests that two seperate processes are involved in the replenishment of Rc and that progesterone inhibits the second phase of replenishment. The binding affinity and specificity of Rc for estrogens following E + P pretreatment were identical to those of the E pretreatment group. Therefore, P does not alter the binding properties but rather the intrauterine level of Rc. Treatment with E on day 4, when Rc levels differ between E and E + P groups, stimulated uterine weight and protein content on day 5 in the E pretreatment group. However, minimal stimulation was observed in the E + P pretreatment group. The quantity of RnE and the time of nuclear retention of RnE following E injection on day 4 was greater in the E group than in the E + P group. The effect of progesterone on Rc replenishment was dose-dependent (range, 0.1-2.5 mg; 1/2 maximal, 0.5 mg). Injection of testosterone propionate (1.0 mg), a weak estrogen antagonist, with E on day 3 resulted in slightly reduced levels of Rc on day 4. This reduction also correlated with a reduced sensitivity to treatment with E on day 4. These data, together with previous studies from our laboratory, suggest that progesterone and other estrogen antagonists such as nafoxidine and testosterone propionate inhibit estrogen action by interfering with the replenishment of Rc, thereby reducing the number of receptor estrogen complexes that are translocated and retained by uterine nuclei."} {"id": "PMID:174900", "title": "Effects of ACTH, dexamethasone, adrenalectomy and stress on cAMP content of adenohypophysis and adrenals in rats.", "content": "The effects of adrenalectomy, ether-laparotomy stress and in vivo administration of either ACTH or dexamethasone on the cAMP levels in the anterior pituitary and the adrenal glands were investigated in male rats. After adrenalectomy or ether-laparotomy stress, an increase of the pituitary cAMP levels was observed. A prior administration of dexamethasone failed to inhibit the increase of the pituitary cAMP levels. Acute administration of dexamethasone increased the cAMP levels in the pituitary. Chronic administration of dexamethasone decreased the cAMP levels in the pituitary, but ACTH did not. These data suggest that cAMP might be involved in the mediation of the hypothalamo-pituitary-adrenal axis.", "contents": "Effects of ACTH, dexamethasone, adrenalectomy and stress on cAMP content of adenohypophysis and adrenals in rats. The effects of adrenalectomy, ether-laparotomy stress and in vivo administration of either ACTH or dexamethasone on the cAMP levels in the anterior pituitary and the adrenal glands were investigated in male rats. After adrenalectomy or ether-laparotomy stress, an increase of the pituitary cAMP levels was observed. A prior administration of dexamethasone failed to inhibit the increase of the pituitary cAMP levels. Acute administration of dexamethasone increased the cAMP levels in the pituitary. Chronic administration of dexamethasone decreased the cAMP levels in the pituitary, but ACTH did not. These data suggest that cAMP might be involved in the mediation of the hypothalamo-pituitary-adrenal axis."} {"id": "PMID:174901", "title": "A receptor site for prolactin in lactating mouse mammary tissues.", "content": "Prolactin iodinated by lactoperoxidase method showed immunologically, electrophoretically and biolo9gically similar properties to native prolactin and possessed enough specific radioactivity for receptor studies. 1251-prolactin was incubated with mouse mammary tissues at 8 days of lactation. Both binding and release of 1251-prolactin depended on incubation time and temperature and were maximal at 37 degrees C. Michaelis constant was estimated to be 1.4 X 10(-9) M from Lineweaver-Burk plot and to be 1.2 X 10(-9) M from id-value of the dose-response curve for displacement with native prolactin. Total number of binding sites for prolactin was 1.38 X 10(-15) mole per mg weight of tissue. Ovine prolactin, human growth hormone and human placental lactogen complete with 1251-prolactin and dose-response curves for these three hormones were all parallel. These results suggest the existence of a specific receptor site with high affinity for prolactin in lactating mouse mammary glands.", "contents": "A receptor site for prolactin in lactating mouse mammary tissues. Prolactin iodinated by lactoperoxidase method showed immunologically, electrophoretically and biolo9gically similar properties to native prolactin and possessed enough specific radioactivity for receptor studies. 1251-prolactin was incubated with mouse mammary tissues at 8 days of lactation. Both binding and release of 1251-prolactin depended on incubation time and temperature and were maximal at 37 degrees C. Michaelis constant was estimated to be 1.4 X 10(-9) M from Lineweaver-Burk plot and to be 1.2 X 10(-9) M from id-value of the dose-response curve for displacement with native prolactin. Total number of binding sites for prolactin was 1.38 X 10(-15) mole per mg weight of tissue. Ovine prolactin, human growth hormone and human placental lactogen complete with 1251-prolactin and dose-response curves for these three hormones were all parallel. These results suggest the existence of a specific receptor site with high affinity for prolactin in lactating mouse mammary glands."} {"id": "PMID:174902", "title": "Effects of calcium ionophore (A-23187) on glucose oxidation and iodide transport in dog thyroid slices.", "content": "A calcium ionophore (A-23187, 20 mug/ml) stimulted 14C-1-glucose oxidation in dog thyroid slices to an extent equivalent to that obtained by the optimal concentration of dibutyryl cyclic AMP (1mM). Furthermore, the ionophore augmented the stimulation by dibutyryl cyclic AMP much more than the simple additive effect. The ionophore also enhanced the effect of TSH, but to a lesser extent. Under conditions where organic binding was blocked, T/M ratio of radioiodine concentration was lowered in slices by the ionophore; the findings similar to those obtained with TSH and dibutyryl cyclic AMP. The ionophore exhibited a slightly depressive effect on the basal cyclic AMP level. The elevation by TSH of cyclic AMP levels was also slightly depressed by the ionophore, but statistically insignificant in most cases. These results indicate that calcium ion may play an important role in the TSH regulation of iodide transport and glucose metabolism in the thyroid, in some cases by augmenting the effects of cyclic AMP.", "contents": "Effects of calcium ionophore (A-23187) on glucose oxidation and iodide transport in dog thyroid slices. A calcium ionophore (A-23187, 20 mug/ml) stimulted 14C-1-glucose oxidation in dog thyroid slices to an extent equivalent to that obtained by the optimal concentration of dibutyryl cyclic AMP (1mM). Furthermore, the ionophore augmented the stimulation by dibutyryl cyclic AMP much more than the simple additive effect. The ionophore also enhanced the effect of TSH, but to a lesser extent. Under conditions where organic binding was blocked, T/M ratio of radioiodine concentration was lowered in slices by the ionophore; the findings similar to those obtained with TSH and dibutyryl cyclic AMP. The ionophore exhibited a slightly depressive effect on the basal cyclic AMP level. The elevation by TSH of cyclic AMP levels was also slightly depressed by the ionophore, but statistically insignificant in most cases. These results indicate that calcium ion may play an important role in the TSH regulation of iodide transport and glucose metabolism in the thyroid, in some cases by augmenting the effects of cyclic AMP."} {"id": "PMID:174903", "title": "5alpha-Dihydrotestosterone binding protein in rat ventral prostate; purification, nuclear incorporation, and subnuclear localization.", "content": "Treatment of cytosol from the rat ventral prostate with cold acetone (-20 degrees C) evoked a 8 approximately 10-fold increase in the binding capacity with 5alpha-dihydrotestosterone (DHT). Starting from the extract of acetone-dried prostate cytosol, some 400 approximately 600-fold purification of the DHT-binding protein complex was acieved by (NH4)2504 fractionation, DEAE-cellulose chromatography and gel- filtration with Sephadex G-200. The purified 3H-DHT-binding protein complex was incorporated into the nuclei from the ventral prostate in a temperature dependent manner. The similar incorporation was also observed in nuclei from the liver and the kidney...", "contents": "5alpha-Dihydrotestosterone binding protein in rat ventral prostate; purification, nuclear incorporation, and subnuclear localization. Treatment of cytosol from the rat ventral prostate with cold acetone (-20 degrees C) evoked a 8 approximately 10-fold increase in the binding capacity with 5alpha-dihydrotestosterone (DHT). Starting from the extract of acetone-dried prostate cytosol, some 400 approximately 600-fold purification of the DHT-binding protein complex was acieved by (NH4)2504 fractionation, DEAE-cellulose chromatography and gel- filtration with Sephadex G-200. The purified 3H-DHT-binding protein complex was incorporated into the nuclei from the ventral prostate in a temperature dependent manner. The similar incorporation was also observed in nuclei from the liver and the kidney..."} {"id": "PMID:174904", "title": "Further experimental results concerning the relationship of muscular exercise and adrenal function.", "content": "The relationship between muscular work and adrenal function was investigated by using daily swimming exercise in the rat. 1. Adrenal in vitro sensitivity to ACTH was found to have increased after six weeks of swimming training 2. In the development of adaptation the main part was played by muscular exercise itself, since a conditioning of the animals merely to the circumstances of swimming failed to stimulate such adaptive changes as seen in the course of regular physical training. 3. Plasma steroid response to certain stressor agents, such as histamine or acute exhaustion (decrease), respectively to ACTH administration (increase) was similar in ACTH-pretreated and regularly exercised animals. 4. In the 6th to 12th weeks of exercise the trained animals developed a lower plasma steroid content at rest than the controls. This feature was retained even four weeks after the cessation of training sessions. Experimental physical training reduced post-exercise steroidemia in the period of adaptation, that is, after the 6th week. After a pause of 4 weeks, however, the post-exercise steroidemia approached again the control values.", "contents": "Further experimental results concerning the relationship of muscular exercise and adrenal function. The relationship between muscular work and adrenal function was investigated by using daily swimming exercise in the rat. 1. Adrenal in vitro sensitivity to ACTH was found to have increased after six weeks of swimming training 2. In the development of adaptation the main part was played by muscular exercise itself, since a conditioning of the animals merely to the circumstances of swimming failed to stimulate such adaptive changes as seen in the course of regular physical training. 3. Plasma steroid response to certain stressor agents, such as histamine or acute exhaustion (decrease), respectively to ACTH administration (increase) was similar in ACTH-pretreated and regularly exercised animals. 4. In the 6th to 12th weeks of exercise the trained animals developed a lower plasma steroid content at rest than the controls. This feature was retained even four weeks after the cessation of training sessions. Experimental physical training reduced post-exercise steroidemia in the period of adaptation, that is, after the 6th week. After a pause of 4 weeks, however, the post-exercise steroidemia approached again the control values."} {"id": "PMID:174905", "title": "Influence of thyrotropin releasing hormone and dibutyryl cyclic adenosine 3',5'-monophosphate on ultrastructure of adenohypophysis in organ culture.", "content": "Ultrastructure of adenohypophysis in organ culture exposed to thyrotropin releasing hormone or dibutyryl cyclic adenosine 3',5'-monophosphate has been investigated. The features of increased secretory activity of glandular cells as well as the occurrence of a strongly osmiophilic substance in the intercellular spaces was observed in cultures exposed to both investigated factors.", "contents": "Influence of thyrotropin releasing hormone and dibutyryl cyclic adenosine 3',5'-monophosphate on ultrastructure of adenohypophysis in organ culture. Ultrastructure of adenohypophysis in organ culture exposed to thyrotropin releasing hormone or dibutyryl cyclic adenosine 3',5'-monophosphate has been investigated. The features of increased secretory activity of glandular cells as well as the occurrence of a strongly osmiophilic substance in the intercellular spaces was observed in cultures exposed to both investigated factors."} {"id": "PMID:174906", "title": "Evocability of a slight positive oestrogen feedback action on LH secretion in castrated and oestrogen-primed men.", "content": "Orchidectomized heterosexual men suffering from prostatic cancer with suppressed serum LH values by oestrogen priming exhibited a slight, but significant surge of LH secretion following oestrogen injection. In contrast, orchidectomized and oestrogen-primed heterosexual men with unsuppressed serum LH levels as well as intact heterosexual men did not display any positive oestrogen feedback action on LH secretion, as it was observed in intact homosexual men.", "contents": "Evocability of a slight positive oestrogen feedback action on LH secretion in castrated and oestrogen-primed men. Orchidectomized heterosexual men suffering from prostatic cancer with suppressed serum LH values by oestrogen priming exhibited a slight, but significant surge of LH secretion following oestrogen injection. In contrast, orchidectomized and oestrogen-primed heterosexual men with unsuppressed serum LH levels as well as intact heterosexual men did not display any positive oestrogen feedback action on LH secretion, as it was observed in intact homosexual men."} {"id": "PMID:174907", "title": "Virus association with wastewater solids.", "content": "The solids produced at an urban wastewater treatment plant, tested semiquantitatively, almost all contained human intestinal viruses. Reoviruses and five or more types of enteroviruses were present. Sludge, digested anaerobically at 30 degrees-32 degrees C, and grit contained measurable levels of viruses. Until reliable means of inactivating the viruses have been developed and implemented, great care should be taken in disposing of these solids.", "contents": "Virus association with wastewater solids. The solids produced at an urban wastewater treatment plant, tested semiquantitatively, almost all contained human intestinal viruses. Reoviruses and five or more types of enteroviruses were present. Sludge, digested anaerobically at 30 degrees-32 degrees C, and grit contained measurable levels of viruses. Until reliable means of inactivating the viruses have been developed and implemented, great care should be taken in disposing of these solids."} {"id": "PMID:174908", "title": "Accumulation of cadmium in rat liver cadmium binding protein following single and repeated cadmium administration.", "content": "The accumulation of cadmium in rat liver cadmium binding protein induced by single and repeated intraperitoneal injections of CdCl2 and the de novo biosynthesis of CdBP were studied by using 109Cd to measure cadmium binding in the CdBP and 35S incorporation as indicator of protein synthesis. The biosynthesis of CdBP is controlled by the cadmium concentrations. For single doses up to 1 mg Cd2+/Kg b.w. about 50% of the cadmium is present in the soluble fraction of liver bound to CdBP and the incorporation of 35S-cysteine is linear with the cadmium concentration. When single doses ranging from 1 to 3 mg Cd2+/Kg b.w. are administered the fractions of both 35S-cysteine and cadmium incorporated into de novo synthesized CdBP gradually decrease. For single doses higher than 3 mg Cd2+/Kg b.w. the biosynthesis capability is maximum and 20 mug Cd/g liver can be incorporated into the de novo biosynthesized CdBP. When rats are treated every day with amounts of cadmium of about 0.8 mg Cd2+/Kg b.w. for up to 8 days a dose-proportional increase in both Cd incorporation and CdBP biosynthesis are observed. This shows a cumulative incorporation of cadmium in the de novo biosynthesized CdBP. Experiments carried out by injecting 65ZnCl2 and 203HgCl2 every day showed that they are not accumulated like cadmium and do not induce the biosynthesis of rat liver CdBP after repeated administration over 7 days.", "contents": "Accumulation of cadmium in rat liver cadmium binding protein following single and repeated cadmium administration. The accumulation of cadmium in rat liver cadmium binding protein induced by single and repeated intraperitoneal injections of CdCl2 and the de novo biosynthesis of CdBP were studied by using 109Cd to measure cadmium binding in the CdBP and 35S incorporation as indicator of protein synthesis. The biosynthesis of CdBP is controlled by the cadmium concentrations. For single doses up to 1 mg Cd2+/Kg b.w. about 50% of the cadmium is present in the soluble fraction of liver bound to CdBP and the incorporation of 35S-cysteine is linear with the cadmium concentration. When single doses ranging from 1 to 3 mg Cd2+/Kg b.w. are administered the fractions of both 35S-cysteine and cadmium incorporated into de novo synthesized CdBP gradually decrease. For single doses higher than 3 mg Cd2+/Kg b.w. the biosynthesis capability is maximum and 20 mug Cd/g liver can be incorporated into the de novo biosynthesized CdBP. When rats are treated every day with amounts of cadmium of about 0.8 mg Cd2+/Kg b.w. for up to 8 days a dose-proportional increase in both Cd incorporation and CdBP biosynthesis are observed. This shows a cumulative incorporation of cadmium in the de novo biosynthesized CdBP. Experiments carried out by injecting 65ZnCl2 and 203HgCl2 every day showed that they are not accumulated like cadmium and do not induce the biosynthesis of rat liver CdBP after repeated administration over 7 days."} {"id": "PMID:174911", "title": "The reduction of plastocyanin by plastoquinol-1 in the presence of chloroplasts. A dark electron transfer reaction involving components between the two photosystems.", "content": "The reduction of plastocyanin by plastoquinol-1 was efficiently catalysed by disrupted chloroplasts or etioplasts in the dark. The reaction was inhibited by 2,5-dibromomethylisopropyl-p-benzo-quinone which inhibits photosynthetic electron transport between plastoquinone and cytochrome f. Evidence is presented that the reduction took place via cytochrome f, and that plastoquinone-9 was not involved. Triton X-100 and organic solvents were inhibitory, but partial fractionation was achieved without loss of activity by density gradient centrifugation in the presence of high digitonin concentrations. All active material contained cytochromes b-559LP and b-563 in addition to cytochrome f, but these b-type cytochromes were not directly involved. Other 1-electron acceptors could be used in place of plastocyanin, for instance ferricyanide and Pseudomonas cytochrome c-551. The reaction can be applied to give a sensitive dark assay for active cytochrome f. It is suggested that cytochrome f possesses two sites for interaction with redox reagents: a hydrophilic site with which plastocyanin reacts by electron transfer and a hydrophobic site with which plastoquinol reacts by hydrogen atom transfer.", "contents": "The reduction of plastocyanin by plastoquinol-1 in the presence of chloroplasts. A dark electron transfer reaction involving components between the two photosystems. The reduction of plastocyanin by plastoquinol-1 was efficiently catalysed by disrupted chloroplasts or etioplasts in the dark. The reaction was inhibited by 2,5-dibromomethylisopropyl-p-benzo-quinone which inhibits photosynthetic electron transport between plastoquinone and cytochrome f. Evidence is presented that the reduction took place via cytochrome f, and that plastoquinone-9 was not involved. Triton X-100 and organic solvents were inhibitory, but partial fractionation was achieved without loss of activity by density gradient centrifugation in the presence of high digitonin concentrations. All active material contained cytochromes b-559LP and b-563 in addition to cytochrome f, but these b-type cytochromes were not directly involved. Other 1-electron acceptors could be used in place of plastocyanin, for instance ferricyanide and Pseudomonas cytochrome c-551. The reaction can be applied to give a sensitive dark assay for active cytochrome f. It is suggested that cytochrome f possesses two sites for interaction with redox reagents: a hydrophilic site with which plastocyanin reacts by electron transfer and a hydrophobic site with which plastoquinol reacts by hydrogen atom transfer."} {"id": "PMID:174912", "title": "Brown adipose tissue mitochondria: recoupling caused by substrate level phosphorylation and extramitochondrial adenosine phosphates.", "content": "1. Uncoupled oxidative phosphorylation in isolated guinea pig brown-adipose-tissue mitochondria is reflected by a low phosphorylation state of adenosine phosphates in the mitochondrial matrix and in the extramitochondrial space during oxidation of succinate or glycerol 1-phosphate in the presence of serum albumin and 100 muM ADP. Recoupling of respiration and phosphorylation in the mitochondria is indicatdd by a dramatic increase in the phosphorylation state of adenine nucleotides in both compartments, when substrates inducing substrate level phosphorylation are respired. In this case ATP/ADP ratios in the extramitochondrial compartment are 10-15 times higher than in the mitochondrial matrix. 2. Recoupling mediated by substrate level phosphorylation depends on the presence of extramitochondrial adenosine phosphate and on intact adenine nucleotide translocation. In the presence of substrate level phosphorylation the amount of extramitochondrial ADP required to restore energy coupling can be extremely low (20 muM ADP or 10 nmol ADP/mg mitochondrial protein respectively). If substrate level phosphorylation is prevented by rotenone or in the presence of atractyloside, 20-50 times higher amounts of extramitochondrial adenine nucleotides are necessary to cause coupled oxidative phosphorylation. The recoupling effect of ATP is significantly stronger than that of ADP. 3. GDP (100 muM) causes a rapid increase of the ATP/ADP ratio in both compartments which is independent of substrate level phosphorylation as well as of the extramitochondrial adenosine phosphate concentration and the adenine nucleotide carrier. 4. The amount of extramitochondrial adenosine phosphate in guinea pig brown-adipose-tissue (18 nmol/mg mitochondrial protein or 2.5 mM respectively) would suffice for recoupling of oxidative phosphorylation mediated by substrate level phosphorylation under conditions in vitro; this suggests that substrate level phosphorylation is of essential importance in brown fat in vivo with respect to energy conditions in the tissue during different states of thermogenesis.", "contents": "Brown adipose tissue mitochondria: recoupling caused by substrate level phosphorylation and extramitochondrial adenosine phosphates. 1. Uncoupled oxidative phosphorylation in isolated guinea pig brown-adipose-tissue mitochondria is reflected by a low phosphorylation state of adenosine phosphates in the mitochondrial matrix and in the extramitochondrial space during oxidation of succinate or glycerol 1-phosphate in the presence of serum albumin and 100 muM ADP. Recoupling of respiration and phosphorylation in the mitochondria is indicatdd by a dramatic increase in the phosphorylation state of adenine nucleotides in both compartments, when substrates inducing substrate level phosphorylation are respired. In this case ATP/ADP ratios in the extramitochondrial compartment are 10-15 times higher than in the mitochondrial matrix. 2. Recoupling mediated by substrate level phosphorylation depends on the presence of extramitochondrial adenosine phosphate and on intact adenine nucleotide translocation. In the presence of substrate level phosphorylation the amount of extramitochondrial ADP required to restore energy coupling can be extremely low (20 muM ADP or 10 nmol ADP/mg mitochondrial protein respectively). If substrate level phosphorylation is prevented by rotenone or in the presence of atractyloside, 20-50 times higher amounts of extramitochondrial adenine nucleotides are necessary to cause coupled oxidative phosphorylation. The recoupling effect of ATP is significantly stronger than that of ADP. 3. GDP (100 muM) causes a rapid increase of the ATP/ADP ratio in both compartments which is independent of substrate level phosphorylation as well as of the extramitochondrial adenosine phosphate concentration and the adenine nucleotide carrier. 4. The amount of extramitochondrial adenosine phosphate in guinea pig brown-adipose-tissue (18 nmol/mg mitochondrial protein or 2.5 mM respectively) would suffice for recoupling of oxidative phosphorylation mediated by substrate level phosphorylation under conditions in vitro; this suggests that substrate level phosphorylation is of essential importance in brown fat in vivo with respect to energy conditions in the tissue during different states of thermogenesis."} {"id": "PMID:174913", "title": "New coenzymically-active soluble and insoluble macromolecular NAD+ derivatives.", "content": "Reaction in dimethyl sulfoxide of nicotinamide 8-bromoadenine dinucleotide with the disodium salt of 3-mercaptopropionic acid afforded nicotinamide-8-(2-carboxyethylthio)adenine dinucleotide, a new NAD+ analogue functionalized at the adenine C-8 position by an omega-carboxylic side chain. Carbodimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexy)-Sepharose) polymers gave the corresponding macromolecular NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine analogue showed a substantial degree of efficiency relative to free NAD+ with yeast alcohol dehydrogenase (47%) but a considerably lower one with rabbit muscle lactate dehydrogenase (3%); the polylysine analogue showed a low degree of efficiency with both enzymes (5-6%).", "contents": "New coenzymically-active soluble and insoluble macromolecular NAD+ derivatives. Reaction in dimethyl sulfoxide of nicotinamide 8-bromoadenine dinucleotide with the disodium salt of 3-mercaptopropionic acid afforded nicotinamide-8-(2-carboxyethylthio)adenine dinucleotide, a new NAD+ analogue functionalized at the adenine C-8 position by an omega-carboxylic side chain. Carbodimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexy)-Sepharose) polymers gave the corresponding macromolecular NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine analogue showed a substantial degree of efficiency relative to free NAD+ with yeast alcohol dehydrogenase (47%) but a considerably lower one with rabbit muscle lactate dehydrogenase (3%); the polylysine analogue showed a low degree of efficiency with both enzymes (5-6%)."} {"id": "PMID:174914", "title": "Kinetics of adenosine 3':5'-monophosphate accumulation in dog thyroid slices.", "content": "Dog thyroid slices have been stimulated in vitro by thyrotropin. The kinetics of adenosine 3':5'-monophosphate (cyclic AMP) accumulation due to the activation of adenylate cyclase were measured. Experimental results have been interpreted by means of a numerical simulation based on a theoretical description of the overall process which consists of three steps: (a) the penetration of thyrotropin in the slices, (b) the binding of the hormone to the specific receptor and the consequent activation of adenylate cyclase, (c) the kinetics of cyclic AMP accumulation in each cell due to the interplay between synthesis and degradation. The numerical values of the parameters needed for the simulation were deduced from separate experiments. Diffusion of thyrotropin in the slices has been calculated from the kinetics of efflux of [3H]sucrose, and with or without albumin. Adenylate cyclase activity and activation by thyrotropin in homogenates and purified membranes were measured. Binding experiments of cyclic AMP on crude extract of dog thyroid lead to the conclusion that the maximal capacity of the specific binding site is close to the cyclic AMP content in resting thyroid cells. The purpose of this paper is to verify the validity of the current concepts about the mechanisms taking place in this process by comparing experimental results and theoretical simulation. It results from the study that for this system the time between the activation of adenylate cyclase and half maximal cyclic AMPaccumulation is equal to 3 min 45 s and the pool of cyclic AMP is renewed three times per minute. It has been also stressed that the thickness of the slices as well as inhibitors of phosphodiesterases change the apparent kinetics of cyclic AMP accumulation.", "contents": "Kinetics of adenosine 3':5'-monophosphate accumulation in dog thyroid slices. Dog thyroid slices have been stimulated in vitro by thyrotropin. The kinetics of adenosine 3':5'-monophosphate (cyclic AMP) accumulation due to the activation of adenylate cyclase were measured. Experimental results have been interpreted by means of a numerical simulation based on a theoretical description of the overall process which consists of three steps: (a) the penetration of thyrotropin in the slices, (b) the binding of the hormone to the specific receptor and the consequent activation of adenylate cyclase, (c) the kinetics of cyclic AMP accumulation in each cell due to the interplay between synthesis and degradation. The numerical values of the parameters needed for the simulation were deduced from separate experiments. Diffusion of thyrotropin in the slices has been calculated from the kinetics of efflux of [3H]sucrose, and with or without albumin. Adenylate cyclase activity and activation by thyrotropin in homogenates and purified membranes were measured. Binding experiments of cyclic AMP on crude extract of dog thyroid lead to the conclusion that the maximal capacity of the specific binding site is close to the cyclic AMP content in resting thyroid cells. The purpose of this paper is to verify the validity of the current concepts about the mechanisms taking place in this process by comparing experimental results and theoretical simulation. It results from the study that for this system the time between the activation of adenylate cyclase and half maximal cyclic AMPaccumulation is equal to 3 min 45 s and the pool of cyclic AMP is renewed three times per minute. It has been also stressed that the thickness of the slices as well as inhibitors of phosphodiesterases change the apparent kinetics of cyclic AMP accumulation."} {"id": "PMID:174915", "title": "Cerebrospinal fluid concentration of cyclic AMP in cerebrovascular diseases.", "content": "Concentration of cyclic adenosine 3',5'-monophosphate (cAMP) and activities of some enzymes were measured in cerebrospinal fluid (CSF) from 38 patients with various cerebrovascular diseases. Cerebral infarction of the carotid area (less than 14 days after the attack) revealed a significant increase in CSF cAMP level in comparison to a transient ischemic attack (TIA) and cephalagia without any pathological findings (control group). A trend towards elevated values was observed also in cerebral hemorrhage, whereas the CSF cAMP concentrations in subarachnoid hemorrhage, TIA, syncope, and cerebral infarction of at least 2 months of duration were in the range of control values. A significant rise in CSF enzyme activities was observed only in hemorrhagic disorders. Hypertensive patients with TIA showed significantly higher CSF cAMP values than normotensive ones. A similar positive correlation between blood pressure and CSF aAMP concentrations was found also in subarachnoid hemorrhage and syncope groups. On the basis of the present results it is suggested that in cerebrovascular diseases CSF cAMP concentration reflects the size and the time of the destruction of cerebral cells, and correlates with hypertension of the patient possibly indicating an increased sympathetic activity.", "contents": "Cerebrospinal fluid concentration of cyclic AMP in cerebrovascular diseases. Concentration of cyclic adenosine 3',5'-monophosphate (cAMP) and activities of some enzymes were measured in cerebrospinal fluid (CSF) from 38 patients with various cerebrovascular diseases. Cerebral infarction of the carotid area (less than 14 days after the attack) revealed a significant increase in CSF cAMP level in comparison to a transient ischemic attack (TIA) and cephalagia without any pathological findings (control group). A trend towards elevated values was observed also in cerebral hemorrhage, whereas the CSF cAMP concentrations in subarachnoid hemorrhage, TIA, syncope, and cerebral infarction of at least 2 months of duration were in the range of control values. A significant rise in CSF enzyme activities was observed only in hemorrhagic disorders. Hypertensive patients with TIA showed significantly higher CSF cAMP values than normotensive ones. A similar positive correlation between blood pressure and CSF aAMP concentrations was found also in subarachnoid hemorrhage and syncope groups. On the basis of the present results it is suggested that in cerebrovascular diseases CSF cAMP concentration reflects the size and the time of the destruction of cerebral cells, and correlates with hypertension of the patient possibly indicating an increased sympathetic activity."} {"id": "PMID:174916", "title": "Olfaction in multiple sclerosis. With a note on the discrepancy between optic and olfactory involvement.", "content": "Serial binary dilutions of amyl acetate and nitrobenzene were used in a double-blind test to determine olfactory acuity of 40 multiple sclerosis (MS) patients. Similar determinations were made on 24 age- and sex-matched controls. Results of repeated measurements on 18 patients indicated that the methodology was reliably reproducible. When mean olfactory threshold on MS patients was compared with that of the controls no differences could be found. Among the MS patients, olfactory threshold did not vary with the presence or absence of optic involvement and correlated poorly with the degree of disability. These results are in disagreement with those of WENDER and SZMEJA who reported olfactory dysfunction in 18 out of 52 MS patients. Our findings are compatible with the observations of ZIMMERMAN and NETSKY who failed to find any plaques in olfactory tracts of MS brains. The significance of this disparity between involvement of optic and olfactory systems, both of which contain central myelin, is discussed. Available biochemical evidence suggests that, as postulated by LUMSDEN, sparing of olfactory tracts may in part be related to the relatively lower basic protein content of these structures.", "contents": "Olfaction in multiple sclerosis. With a note on the discrepancy between optic and olfactory involvement. Serial binary dilutions of amyl acetate and nitrobenzene were used in a double-blind test to determine olfactory acuity of 40 multiple sclerosis (MS) patients. Similar determinations were made on 24 age- and sex-matched controls. Results of repeated measurements on 18 patients indicated that the methodology was reliably reproducible. When mean olfactory threshold on MS patients was compared with that of the controls no differences could be found. Among the MS patients, olfactory threshold did not vary with the presence or absence of optic involvement and correlated poorly with the degree of disability. These results are in disagreement with those of WENDER and SZMEJA who reported olfactory dysfunction in 18 out of 52 MS patients. Our findings are compatible with the observations of ZIMMERMAN and NETSKY who failed to find any plaques in olfactory tracts of MS brains. The significance of this disparity between involvement of optic and olfactory systems, both of which contain central myelin, is discussed. Available biochemical evidence suggests that, as postulated by LUMSDEN, sparing of olfactory tracts may in part be related to the relatively lower basic protein content of these structures."} {"id": "PMID:174917", "title": "Effect of convulsions and anticonvulsive drugs on cerebrospinal fluid cyclic AMP in rabbits.", "content": "Cyclic adenosine 3',5'-monophosphate (cAMP) concentration and aspartate amino transferase (ASAT or GOT) activity were measured from cerebrospinal fluid (CSF) of rabbits before and after electrically induced convulsions. The convulsions caused a significant increase in CSF cAMP concentration. The treatment with phenobarbital, diphenylhydantoin and carbamazepine for 7 days decreased the basal cAMP values in CSF and partly inhibited the rise after the convulsions. The alterations in ASAT activity were parallel, but less striking. The present results suggest the involvement of cAMP in epileptic discharge and in the mechanism of action of anticonvulsants.", "contents": "Effect of convulsions and anticonvulsive drugs on cerebrospinal fluid cyclic AMP in rabbits. Cyclic adenosine 3',5'-monophosphate (cAMP) concentration and aspartate amino transferase (ASAT or GOT) activity were measured from cerebrospinal fluid (CSF) of rabbits before and after electrically induced convulsions. The convulsions caused a significant increase in CSF cAMP concentration. The treatment with phenobarbital, diphenylhydantoin and carbamazepine for 7 days decreased the basal cAMP values in CSF and partly inhibited the rise after the convulsions. The alterations in ASAT activity were parallel, but less striking. The present results suggest the involvement of cAMP in epileptic discharge and in the mechanism of action of anticonvulsants."} {"id": "PMID:174918", "title": "Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.", "content": "In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.", "contents": "Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics. In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism."} {"id": "PMID:174919", "title": "The effect of imidazole on the isometric contractility of the isolated hemidiaphragm of the rat.", "content": "Imidazole (0.73-15.9mM) was found to increase both tension developed Td and the maximum rats of rise of tension, dT/dtmax, in the isolated hemidiaphragm of the rat during indirect stimulation. Similar effects were obtained during direct stimulation and in the presence of d-tubocurarine. Imidazole (0.73-22 mM) antagonized the action of d-tubocurarine. This effect was particularly pronounced in preparations pretreated with imidazole. Propranolol did not significantly change the action of imidazole on Td and dT/dtmax during direct stimulation. Similarly, propranolol did not affect the action of low concentrations of imidazole during indirect stimulation. When present in the bath for periods of time longer than 15 min, propranolol significantly depressed the effect of even high concentrations of imidazole on Td and dT/dtmax during indirect stimulation. Histamine (0.18-0.91 mM) did not affect either Td or dT/dtmax. In the experiments in vivo, imidazole (12.5-100 mg/kg) produced a small increase both in Td and dT/dtmax of the gastrocnemius muscle during sciatic nerve stimulation. The available evidence indicates that the action of imidazole on Td and dT/dtmax is not connected with its action on phosphodiesterase, but it is most probably due to a direct action on the muscle.", "contents": "The effect of imidazole on the isometric contractility of the isolated hemidiaphragm of the rat. Imidazole (0.73-15.9mM) was found to increase both tension developed Td and the maximum rats of rise of tension, dT/dtmax, in the isolated hemidiaphragm of the rat during indirect stimulation. Similar effects were obtained during direct stimulation and in the presence of d-tubocurarine. Imidazole (0.73-22 mM) antagonized the action of d-tubocurarine. This effect was particularly pronounced in preparations pretreated with imidazole. Propranolol did not significantly change the action of imidazole on Td and dT/dtmax during direct stimulation. Similarly, propranolol did not affect the action of low concentrations of imidazole during indirect stimulation. When present in the bath for periods of time longer than 15 min, propranolol significantly depressed the effect of even high concentrations of imidazole on Td and dT/dtmax during indirect stimulation. Histamine (0.18-0.91 mM) did not affect either Td or dT/dtmax. In the experiments in vivo, imidazole (12.5-100 mg/kg) produced a small increase both in Td and dT/dtmax of the gastrocnemius muscle during sciatic nerve stimulation. The available evidence indicates that the action of imidazole on Td and dT/dtmax is not connected with its action on phosphodiesterase, but it is most probably due to a direct action on the muscle."} {"id": "PMID:174920", "title": "[Pathological studies on corynebacterial ulcerative entero-colitis in rats treated with ACTH (author's transl)].", "content": "Ulcerative entero-colitis was developed in 6-week-old male Sprague-Dawley rats treated daily with ACTH (4 mg/kg. s. c.) as well as necrotic purulent lesions in liver, kidney, lung or heart. Incidence of ulcerative lesions was 6.3% in Farm-A rats and 56% in Farm-B rats. Although ulcerative lesions were mostly observed in cecum, the similar lesions were also detected in distal ileum or proximal colon in some cases. Histologically, the lesions were characterized by focal necrosis demarcated from surrounding normal tissue containing a number of clumps of bacteria and cellular debris. Bacteriological examination revealed that provocation of Coryne-bacterium kutscheri by ACTH-treatment resulted in appearance of the lesions. By means of intravenous or intraperitoneal inoculation with the strain isolated from lesion similar lesions were produced in the cecum of inoculated rats under the ACTH-treatment.", "contents": "[Pathological studies on corynebacterial ulcerative entero-colitis in rats treated with ACTH (author's transl)]. Ulcerative entero-colitis was developed in 6-week-old male Sprague-Dawley rats treated daily with ACTH (4 mg/kg. s. c.) as well as necrotic purulent lesions in liver, kidney, lung or heart. Incidence of ulcerative lesions was 6.3% in Farm-A rats and 56% in Farm-B rats. Although ulcerative lesions were mostly observed in cecum, the similar lesions were also detected in distal ileum or proximal colon in some cases. Histologically, the lesions were characterized by focal necrosis demarcated from surrounding normal tissue containing a number of clumps of bacteria and cellular debris. Bacteriological examination revealed that provocation of Coryne-bacterium kutscheri by ACTH-treatment resulted in appearance of the lesions. By means of intravenous or intraperitoneal inoculation with the strain isolated from lesion similar lesions were produced in the cecum of inoculated rats under the ACTH-treatment."} {"id": "PMID:174929", "title": "Extracellular Ca2+ and Mg2+ and cellular metabolism of phospholipids.", "content": "High extracellular concentration of Ca2+ inhibits the incorporation of 32P into the cellular phospholipids. This effect is more significant in neoplastic than in normal cells, and it is accompanied by an increase of the percentual incorporation into the lecithin fraction.", "contents": "Extracellular Ca2+ and Mg2+ and cellular metabolism of phospholipids. High extracellular concentration of Ca2+ inhibits the incorporation of 32P into the cellular phospholipids. This effect is more significant in neoplastic than in normal cells, and it is accompanied by an increase of the percentual incorporation into the lecithin fraction."} {"id": "PMID:174930", "title": "[Stability of some bradykinin analogues against kininase II (author's transl)].", "content": "Some analogues of bradykinin, especially with replacements by other amino acids of phenylalanine in position 8, have been investigated for enzymatic stability against kininase II from rat duodenum microsomes and rat uterus plasma membranes, respectively. As compared with bradykinin, two of the analogues, [8-erythro-beta-phenylserine]- and [8-erythro-alpha-Amino-beta-phenylbutyric acid]-Bradykinin were stable to enzymatic degradation. Therefore, the latter may be used for studies in hormone-receptor interaction.", "contents": "[Stability of some bradykinin analogues against kininase II (author's transl)]. Some analogues of bradykinin, especially with replacements by other amino acids of phenylalanine in position 8, have been investigated for enzymatic stability against kininase II from rat duodenum microsomes and rat uterus plasma membranes, respectively. As compared with bradykinin, two of the analogues, [8-erythro-beta-phenylserine]- and [8-erythro-alpha-Amino-beta-phenylbutyric acid]-Bradykinin were stable to enzymatic degradation. Therefore, the latter may be used for studies in hormone-receptor interaction."} {"id": "PMID:174931", "title": "Penetration of phospholipases A2 and C into the squid (Loligo pealii) giant axon.", "content": "Following 1 h exposure, the level of phospholipase A2 penetration into the axoplasm of the squid giant axon was 107 to 350% of that in the external media; corresponding values for phospholipase C were 18 to 31%. Phospholipases can therefore be used to study phospholipid function in axons since they can penetrate through connective tissue and Schwann cell to reach the axolemma.", "contents": "Penetration of phospholipases A2 and C into the squid (Loligo pealii) giant axon. Following 1 h exposure, the level of phospholipase A2 penetration into the axoplasm of the squid giant axon was 107 to 350% of that in the external media; corresponding values for phospholipase C were 18 to 31%. Phospholipases can therefore be used to study phospholipid function in axons since they can penetrate through connective tissue and Schwann cell to reach the axolemma."} {"id": "PMID:174932", "title": "Opposite effects of vasotocin injected intrapituitarly and intraventricularly on corticotropin release in mice.", "content": "A single injection of 10 pg synthetic arginine vasotocin into the pituitary significantly potentiated adrenal hypertrophy produced in male mice by unilateral adrenalectomy, whereas the same concentration injected into the 3rd ventricle produced adrenal atrophy.", "contents": "Opposite effects of vasotocin injected intrapituitarly and intraventricularly on corticotropin release in mice. A single injection of 10 pg synthetic arginine vasotocin into the pituitary significantly potentiated adrenal hypertrophy produced in male mice by unilateral adrenalectomy, whereas the same concentration injected into the 3rd ventricle produced adrenal atrophy."} {"id": "PMID:174933", "title": "[Study of the mitotic activity during the preneoplastic period in the liver of rats treated by diethylnitrosamine (author's transl)].", "content": "The chronic administration of diethylnitrosamine in drinking water induces liver tumors in the rat. The preneoplastic period may be divided in two phases differing mainly in the loss of circadian control of mitotic activity in hepatocytes.", "contents": "[Study of the mitotic activity during the preneoplastic period in the liver of rats treated by diethylnitrosamine (author's transl)]. The chronic administration of diethylnitrosamine in drinking water induces liver tumors in the rat. The preneoplastic period may be divided in two phases differing mainly in the loss of circadian control of mitotic activity in hepatocytes."} {"id": "PMID:174934", "title": "Free and sulfoconjugated dehydroepiandrosterone, cyclic adenosime-3',5'-monophosphate, and free estriol in maternal and cord blood.", "content": "When free DHEA, its sulfatide, and sulfate were assayed in maternal plasma as well as in umbilical cord arterial and venous plasma, rather high concentrations were found in either fraction from cord arterial plasma, reflecting the fetal contribution not only of free DHEA and DHEA sulfate, but also of the lipophile steroid sulfatide. Since high DHEA levels were associated with elevated c-AMP concentrations, a certain interrelationship of both parameters is indicated. In the course of delivery, a rapid decrease of free estriol in maternal plasma was observed. Higher concentration of free estriol in umbilical venous plasma pointed at its placental biosynthesis from fetal precursors.", "contents": "Free and sulfoconjugated dehydroepiandrosterone, cyclic adenosime-3',5'-monophosphate, and free estriol in maternal and cord blood. When free DHEA, its sulfatide, and sulfate were assayed in maternal plasma as well as in umbilical cord arterial and venous plasma, rather high concentrations were found in either fraction from cord arterial plasma, reflecting the fetal contribution not only of free DHEA and DHEA sulfate, but also of the lipophile steroid sulfatide. Since high DHEA levels were associated with elevated c-AMP concentrations, a certain interrelationship of both parameters is indicated. In the course of delivery, a rapid decrease of free estriol in maternal plasma was observed. Higher concentration of free estriol in umbilical venous plasma pointed at its placental biosynthesis from fetal precursors."} {"id": "PMID:174935", "title": "Adenovirus type 12 infection of defined mouse-human hybrid cell clones.", "content": "Human adenovirus type 12 does not multiply in mouse cells; only viral T-antigen is detected. Mouse-human cell hybrid clones containing human chromosomes A3, B5, C7, C11, C12, D14, E17, F19 and F20, support synthesis of adenovirus DNA and capsid antigens.", "contents": "Adenovirus type 12 infection of defined mouse-human hybrid cell clones. Human adenovirus type 12 does not multiply in mouse cells; only viral T-antigen is detected. Mouse-human cell hybrid clones containing human chromosomes A3, B5, C7, C11, C12, D14, E17, F19 and F20, support synthesis of adenovirus DNA and capsid antigens."} {"id": "PMID:174936", "title": "Effects of dibutyryl cyclic AMP on cultured brain cells from chick embryos of different ages.", "content": "The effect of dibutyryl cyclic AMP on cultivated astroblasts from 8-, 12- and 15-day-old chick embryo brain has been studied. The results show that these cells must have reached some degree of maturation in ovo to become morphologically differentiated by the cyclic nucleotide.", "contents": "Effects of dibutyryl cyclic AMP on cultured brain cells from chick embryos of different ages. The effect of dibutyryl cyclic AMP on cultivated astroblasts from 8-, 12- and 15-day-old chick embryo brain has been studied. The results show that these cells must have reached some degree of maturation in ovo to become morphologically differentiated by the cyclic nucleotide."} {"id": "PMID:174937", "title": "Autoradiographic study of the penetration of non-histone chromatin proteins into differentiating cells.", "content": "Attention has previously been drawn to a specific effect of NHCP on embryonic Pleurodeles cell differentiation. With a modified NHCP labelling technique, autoradiography has revealed a cytoplasmic concentration of labelled NHCP and has not revealed any difference between homospecific and heterospecific NHCP penetration.", "contents": "Autoradiographic study of the penetration of non-histone chromatin proteins into differentiating cells. Attention has previously been drawn to a specific effect of NHCP on embryonic Pleurodeles cell differentiation. With a modified NHCP labelling technique, autoradiography has revealed a cytoplasmic concentration of labelled NHCP and has not revealed any difference between homospecific and heterospecific NHCP penetration."} {"id": "PMID:174938", "title": "The influence of MuLV and SV40 viruses on senescence in mouse fibroblasts in vitro.", "content": "Mouse cells productively infected with Moloney leukaemia virus (MuLV) underwent senescence in a manner similar to control cells, although they recovered more readily as an established line. Rapidly growing cell lines were also obtained following simian virus 40 (SV40) infection of senescent cells. However, superinfection of senescent MuLV-producing cells by SV40 led to slower growing cells with a reduced output of infectious MuLV.", "contents": "The influence of MuLV and SV40 viruses on senescence in mouse fibroblasts in vitro. Mouse cells productively infected with Moloney leukaemia virus (MuLV) underwent senescence in a manner similar to control cells, although they recovered more readily as an established line. Rapidly growing cell lines were also obtained following simian virus 40 (SV40) infection of senescent cells. However, superinfection of senescent MuLV-producing cells by SV40 led to slower growing cells with a reduced output of infectious MuLV."} {"id": "PMID:174957", "title": "Matrix vesicle heterogeneity: possible morphogenetic functions for matrix vesicles.", "content": "Extracellular membranous matrix vesicles were localized and described using electronmicroscopy during chondrogenesis, osteogenesis, and dentinogenesis. Evidence indicates that matrix vesicles in each of these specific tissue types function to concentrate and transport ions and enzymes which serve as nucleation sites for the mineralization of hydroxylapatite. We have examined different developmental stages of Meckel's cartilage, alveolar bone and epithelial-mesenchymal interactions associated with tooth formation in newborn mice. These ultrastructural studies indicate matrix vesicle heterogeneity. Whereas most matrix vesicles contain alkaline phosphatase activity during cartilage, bone and dentine mineralization, in earlier developmental stages matrix vesicles contain acid phosphatase activities and little, if any, alkaline phosphatase. Tissue type, specific developmental stage, and ultrastructural criteria indicate various \"classes\" of matrix vesicles. During epithelial-mesenchymal interactions in tooth development, mesenchymal cells (preodontoblasts) appear to be the source of matrix vesicles as indicated by the complementarity between H-2 histocompatibility alloantigen specificity on the cell surface and that of the matrix vesicle outer surface; matrix vesicles are limited by a trilaminar membrane derived from the mesenchymal cells. Some of the vesicles located adjacent to dividing inner enamel epithelial cells contain RNA's as determined by electron microscopic autoradiography in situ, as well as by direct biochemical assays. We postulate that matrix vesicles have many different and important biological functions, one of which may be to mediate developmental information from mesenchyme to epithelia during \"instructive\" stages of tooth development.", "contents": "Matrix vesicle heterogeneity: possible morphogenetic functions for matrix vesicles. Extracellular membranous matrix vesicles were localized and described using electronmicroscopy during chondrogenesis, osteogenesis, and dentinogenesis. Evidence indicates that matrix vesicles in each of these specific tissue types function to concentrate and transport ions and enzymes which serve as nucleation sites for the mineralization of hydroxylapatite. We have examined different developmental stages of Meckel's cartilage, alveolar bone and epithelial-mesenchymal interactions associated with tooth formation in newborn mice. These ultrastructural studies indicate matrix vesicle heterogeneity. Whereas most matrix vesicles contain alkaline phosphatase activity during cartilage, bone and dentine mineralization, in earlier developmental stages matrix vesicles contain acid phosphatase activities and little, if any, alkaline phosphatase. Tissue type, specific developmental stage, and ultrastructural criteria indicate various \"classes\" of matrix vesicles. During epithelial-mesenchymal interactions in tooth development, mesenchymal cells (preodontoblasts) appear to be the source of matrix vesicles as indicated by the complementarity between H-2 histocompatibility alloantigen specificity on the cell surface and that of the matrix vesicle outer surface; matrix vesicles are limited by a trilaminar membrane derived from the mesenchymal cells. Some of the vesicles located adjacent to dividing inner enamel epithelial cells contain RNA's as determined by electron microscopic autoradiography in situ, as well as by direct biochemical assays. We postulate that matrix vesicles have many different and important biological functions, one of which may be to mediate developmental information from mesenchyme to epithelia during \"instructive\" stages of tooth development."} {"id": "PMID:174958", "title": "[Impulse activity of neurons in the rabbit sensory-motor cortex during recruitment].", "content": "In unanesthetized rabbits, recruiting response to low-frequency stimulation of the thalamic center medial was followed by a change in the overall level of neuronal activity in the sensory-motor cortex lasting throughout the stimulation, and a change in the firing rate related to spindles of the response. Adoption of the thalamic stimulation rhythm by cortical neurons could be observed either during the whole period of stimulation or in relation to phases of the recruiting response. These factors of influence of unspecific thalamic structures on neuronal activity in the hemispheres during recruiting response are relatively independent of each other. In contrast with data obtained in anesthetized animals, in chronic conditions unspecific structures exert heterogeneous mainly inhibitory influence on the spike activity of cortical neurons.", "contents": "[Impulse activity of neurons in the rabbit sensory-motor cortex during recruitment]. In unanesthetized rabbits, recruiting response to low-frequency stimulation of the thalamic center medial was followed by a change in the overall level of neuronal activity in the sensory-motor cortex lasting throughout the stimulation, and a change in the firing rate related to spindles of the response. Adoption of the thalamic stimulation rhythm by cortical neurons could be observed either during the whole period of stimulation or in relation to phases of the recruiting response. These factors of influence of unspecific thalamic structures on neuronal activity in the hemispheres during recruiting response are relatively independent of each other. In contrast with data obtained in anesthetized animals, in chronic conditions unspecific structures exert heterogeneous mainly inhibitory influence on the spike activity of cortical neurons."} {"id": "PMID:174959", "title": "[The influence of oxytocin on the membrane potentials of mammary gland secretory cells].", "content": "The effect of oxytocine and its combinations with the acetylcholine, adrenaline, atropin, and prozerin on the level of membrane potential of mammary secretory cells was studied. Short oxytocine application (5-10(-4) ME/ml) evoked hyperpolarization of the contraluminal membrane (12+/-1 mV for 54+/-5 sec). Their response was increased by joint application of acetylcholine or proserine and decreased by preliminary application of atropin. Adrenaline increased or decreased the amplitude of the membrane potential's changes and considerably reduced the duration of the oxytocine reaction. Existence of oxytocine receptors was supposed on the membrane of secretory cells, as well as the possibility of acetylcholine and adrenaline effects on the structure of oxytocine receptors or the interaction of adreno--and cholinergic receptors with the oxytocine those.", "contents": "[The influence of oxytocin on the membrane potentials of mammary gland secretory cells]. The effect of oxytocine and its combinations with the acetylcholine, adrenaline, atropin, and prozerin on the level of membrane potential of mammary secretory cells was studied. Short oxytocine application (5-10(-4) ME/ml) evoked hyperpolarization of the contraluminal membrane (12+/-1 mV for 54+/-5 sec). Their response was increased by joint application of acetylcholine or proserine and decreased by preliminary application of atropin. Adrenaline increased or decreased the amplitude of the membrane potential's changes and considerably reduced the duration of the oxytocine reaction. Existence of oxytocine receptors was supposed on the membrane of secretory cells, as well as the possibility of acetylcholine and adrenaline effects on the structure of oxytocine receptors or the interaction of adreno--and cholinergic receptors with the oxytocine those."} {"id": "PMID:174960", "title": "[Cutaneous leishmaniasis: ultrastructural study (author's transl)].", "content": "While in general agreement with previous searchers, the authors direct their attention at peculiar or unknown structures such as: a huge phagosome sometimes loaded with a paracristalline rod; an occasional set of parallel microtubules along the reservoir; eventual duplication of the blepharoplast and even of the flagellum. There appear to be some 90 microtubules in the hyaloplasm of tleishmania tropica.", "contents": "[Cutaneous leishmaniasis: ultrastructural study (author's transl)]. While in general agreement with previous searchers, the authors direct their attention at peculiar or unknown structures such as: a huge phagosome sometimes loaded with a paracristalline rod; an occasional set of parallel microtubules along the reservoir; eventual duplication of the blepharoplast and even of the flagellum. There appear to be some 90 microtubules in the hyaloplasm of tleishmania tropica."} {"id": "PMID:174962", "title": "Effects of 25-hydroxycholesterol and aminoglutethimide in isolated rat adrenal cells. A model for congenital lipoid adrenal hyperplasia?", "content": "The production of corticosterone from 25-hydroxycholesterol by isolated rat adrenal cells is inhibited by aminoglutethimide phosphate (AGI); half-maximal inhibition is obtained at ca. 10 muM. AGI also inhibits ACTH-stimulated steroid production from endogeneous substrates; here half-maximal inhibition is obtained with ca. 40 muM AGI. In the presence of ACTH + AGI, 25-hydroxycholesterol causes additive inhibition. This effect of 25-hydroxycholesterol is dose-dependent. ACTH-stimulated steroid production from endogeneous substrates is partially inhibited by 5-cholene-3 beta,24-diol. These results may just reflect substrate competition for the side-chain cleaving system or may be due to some seocndary toxic effect on the cells.", "contents": "Effects of 25-hydroxycholesterol and aminoglutethimide in isolated rat adrenal cells. A model for congenital lipoid adrenal hyperplasia? The production of corticosterone from 25-hydroxycholesterol by isolated rat adrenal cells is inhibited by aminoglutethimide phosphate (AGI); half-maximal inhibition is obtained at ca. 10 muM. AGI also inhibits ACTH-stimulated steroid production from endogeneous substrates; here half-maximal inhibition is obtained with ca. 40 muM AGI. In the presence of ACTH + AGI, 25-hydroxycholesterol causes additive inhibition. This effect of 25-hydroxycholesterol is dose-dependent. ACTH-stimulated steroid production from endogeneous substrates is partially inhibited by 5-cholene-3 beta,24-diol. These results may just reflect substrate competition for the side-chain cleaving system or may be due to some seocndary toxic effect on the cells."} {"id": "PMID:174963", "title": "Rapid interaction of prolactin with mouse mammary gland explants.", "content": "Exposure of mouse mammary gland explants to prolactin at 0 degrees C, for periods as brief as 10 seconds, caused a stimulation of labeled uridine incorporation into RNA during a subsequent incubation for 4 h at 37 degrees C. Furthermore, a 2-h wash of the prolactin-exposed explants in media at 0 degrees C did not attenuate the hormonal effect. A similar exposure of explants to insulin, followed by a 2-h wash at 0 degrees C, caused the abolition of the insulin stimulation of labeled uridine incorporation into RNA. The results suggest that there is a rapid and relatively stable interaction of prolactin with the mammary gland, while the interaction of insulin with this tissue would appear to be less stable.", "contents": "Rapid interaction of prolactin with mouse mammary gland explants. Exposure of mouse mammary gland explants to prolactin at 0 degrees C, for periods as brief as 10 seconds, caused a stimulation of labeled uridine incorporation into RNA during a subsequent incubation for 4 h at 37 degrees C. Furthermore, a 2-h wash of the prolactin-exposed explants in media at 0 degrees C did not attenuate the hormonal effect. A similar exposure of explants to insulin, followed by a 2-h wash at 0 degrees C, caused the abolition of the insulin stimulation of labeled uridine incorporation into RNA. The results suggest that there is a rapid and relatively stable interaction of prolactin with the mammary gland, while the interaction of insulin with this tissue would appear to be less stable."} {"id": "PMID:174964", "title": "FSH stimulation of DNA synthesis in Sertoli cells in culture.", "content": "The incorporation of [2H]thymidine into nuclear DNA was investigated in cultured Sertoli cells prepared from testes of 20-day-old rats. Addition of follicle-stimulating hormone (FSH) or dibutyryl cyclic, 3',5'-adenosine monophosphate (DBCAMP) to the culture medium greatly increased incorporation, expressed either as total amounts of [3H]thymidine incorporated per mug DNA or as the percentage of Sertoli cells with labeled nuclear DNA. No stimulation was observed in cells cultured in the presence of testosterone, insulin or cyclic 3',5'-GMP (cGMP). Light and electron microscopic autoradiographic analysis was employed to establish the identity of Sertoli cells having labeled nuclear DNA. Contaminating spermatogonia, which also took up labeled [3H]thymidine, were excluded from cell counts. In addition, Sertoli cells prepared from testes of irradiated 20-day-old germinal cell depleted rats were also observed to incorporate more [3H]thymidine into nuclear DNA when cultured in a chemically defined medium in the presence of FSH. DNA synthesis was abolished by prior treatment of cells with cytosine arabinoside. In separate experiments, the incorporation of [3H]thymidine into DNA of peritubular myoid cells was shown to be independent of FSH or dbcAMP.", "contents": "FSH stimulation of DNA synthesis in Sertoli cells in culture. The incorporation of [2H]thymidine into nuclear DNA was investigated in cultured Sertoli cells prepared from testes of 20-day-old rats. Addition of follicle-stimulating hormone (FSH) or dibutyryl cyclic, 3',5'-adenosine monophosphate (DBCAMP) to the culture medium greatly increased incorporation, expressed either as total amounts of [3H]thymidine incorporated per mug DNA or as the percentage of Sertoli cells with labeled nuclear DNA. No stimulation was observed in cells cultured in the presence of testosterone, insulin or cyclic 3',5'-GMP (cGMP). Light and electron microscopic autoradiographic analysis was employed to establish the identity of Sertoli cells having labeled nuclear DNA. Contaminating spermatogonia, which also took up labeled [3H]thymidine, were excluded from cell counts. In addition, Sertoli cells prepared from testes of irradiated 20-day-old germinal cell depleted rats were also observed to incorporate more [3H]thymidine into nuclear DNA when cultured in a chemically defined medium in the presence of FSH. DNA synthesis was abolished by prior treatment of cells with cytosine arabinoside. In separate experiments, the incorporation of [3H]thymidine into DNA of peritubular myoid cells was shown to be independent of FSH or dbcAMP."} {"id": "PMID:174965", "title": "Characterization of the protein kinases in a transplantable islet cell tumor of the Syrian hamster.", "content": "The protein kinase activities of a transplantable, insulin-producing hamster islet cell tumor were characterized using gel filtration, sucrose density gradient centrifugation and acrylamide gel electrophoresis. The post-microsomal supernatant fluid contains 70-80% of the protein kinase activity present in crude homogenates. A cAMP-dependent protein kinase, PK I (Mr 170,000), represents 25% of the soluble protein kinase activity assayed with protamine as substrate. It dissociates in the presence of cAMP into a cAMP-binding protein, R2 (Mr 90,000) and a catalytic subunit C (Mr 33,000). The dissociation induced by cAMP seems to be facilitated by the addition of Mg2+ and ATP. The regulatory subunit, R2, changes its gel filtration pattern in the presence of 0.5 M NaCl suggesting dissociation into a smaller subunit, R1 (Mr 44,000). By analogy with purified beef heart protein kinase (Erlichman et al., 1973) and skeletal muscle protein kinase, PK I. The presence in crude homogenates of a free cAMP-binding protein indistinguishable from the R2 derived by dissociation of PK I, suggests that PK I is partially dissociated in vivo. A cAMP-independent (casein) kinase (Mr 210,000) elutes with PK I on columns of Sepharose 6B. Another cAMP-independent protein kinase, PK II (Mr 88,000), is the predominatn form of soluble protein kinase accounting for approximately 75% of the soluble protein kinase activity detected using protaimine as substrate. This cAMP-independent protein kinase changes its gel filtration pattern in the presence of 0.5 M NaCl giving rise to a form which appears to have the same Mr (33,000) as the catalytic subunit of PK I. Studies comparing the catalytic subunit C of PK I with PK II and its salt-induced smaller molecular form demonstrate facile association of C with the cAMP-binding protein of purified bovine heart protein kinase to yield a hybrid holoenzyme, whereas PK II and its smaller form fail to recombine in this fashion. The 33,000 dalton forms derived from PK I (by cAMP) and PK II (by salt) also show different substrate specificities. It would appear, therefore, that pK II is a cAMP-independent protein kinase unrelated to PK I.", "contents": "Characterization of the protein kinases in a transplantable islet cell tumor of the Syrian hamster. The protein kinase activities of a transplantable, insulin-producing hamster islet cell tumor were characterized using gel filtration, sucrose density gradient centrifugation and acrylamide gel electrophoresis. The post-microsomal supernatant fluid contains 70-80% of the protein kinase activity present in crude homogenates. A cAMP-dependent protein kinase, PK I (Mr 170,000), represents 25% of the soluble protein kinase activity assayed with protamine as substrate. It dissociates in the presence of cAMP into a cAMP-binding protein, R2 (Mr 90,000) and a catalytic subunit C (Mr 33,000). The dissociation induced by cAMP seems to be facilitated by the addition of Mg2+ and ATP. The regulatory subunit, R2, changes its gel filtration pattern in the presence of 0.5 M NaCl suggesting dissociation into a smaller subunit, R1 (Mr 44,000). By analogy with purified beef heart protein kinase (Erlichman et al., 1973) and skeletal muscle protein kinase, PK I. The presence in crude homogenates of a free cAMP-binding protein indistinguishable from the R2 derived by dissociation of PK I, suggests that PK I is partially dissociated in vivo. A cAMP-independent (casein) kinase (Mr 210,000) elutes with PK I on columns of Sepharose 6B. Another cAMP-independent protein kinase, PK II (Mr 88,000), is the predominatn form of soluble protein kinase accounting for approximately 75% of the soluble protein kinase activity detected using protaimine as substrate. This cAMP-independent protein kinase changes its gel filtration pattern in the presence of 0.5 M NaCl giving rise to a form which appears to have the same Mr (33,000) as the catalytic subunit of PK I. Studies comparing the catalytic subunit C of PK I with PK II and its salt-induced smaller molecular form demonstrate facile association of C with the cAMP-binding protein of purified bovine heart protein kinase to yield a hybrid holoenzyme, whereas PK II and its smaller form fail to recombine in this fashion. The 33,000 dalton forms derived from PK I (by cAMP) and PK II (by salt) also show different substrate specificities. It would appear, therefore, that pK II is a cAMP-independent protein kinase unrelated to PK I."} {"id": "PMID:174966", "title": "LH- and FSH-stimulating of adenylate cyclase in seminiferous tubules from young rats: functional FSH and LH receptors unmasked by homogenization.", "content": "LH- and FSH-sensitive adenylate cyclase activity was present in homogenates of whole testis tissue as well as in microdissected seminiferous tubules derived from young rats. In homogenates of seminiferous tubules a single adenylate cyclase appears to interact with both LH and FSH through separate hormone-specific receptors. Disruption of testis tissue by homogenization exposes functional FSH and LH receptors which are inaccessible to the hormones in intact cell preparations. These results indicate that in certain seminiferous tubule cell types only a fraction of the total functional receptors present is accessible to the cell surface for interaction with hormone.", "contents": "LH- and FSH-stimulating of adenylate cyclase in seminiferous tubules from young rats: functional FSH and LH receptors unmasked by homogenization. LH- and FSH-sensitive adenylate cyclase activity was present in homogenates of whole testis tissue as well as in microdissected seminiferous tubules derived from young rats. In homogenates of seminiferous tubules a single adenylate cyclase appears to interact with both LH and FSH through separate hormone-specific receptors. Disruption of testis tissue by homogenization exposes functional FSH and LH receptors which are inaccessible to the hormones in intact cell preparations. These results indicate that in certain seminiferous tubule cell types only a fraction of the total functional receptors present is accessible to the cell surface for interaction with hormone."} {"id": "PMID:174967", "title": "Gastric antisecretory and antiulcer properties of PGE2, 15-methyl PGE2, and 16, 16-dimethyl PGE2. Intravenous, oral and intrajejunal administration.", "content": "15-Methyl PGE2 and 16,16-dimethyl PGE2 were found (1) to be 40 and 100 times, respectively, more potent than PGE2 after intravenous administration in inhibiting histamine-stimulated gastric secretion in dogs with a denervated (Heidenhain) gastric pouch, (2) to be active orally and intrajejunally, whereas PGE2 was inactive, and (3) to exert antisecretory activity for longer duration than PGE2. 16,16-Dimethyl PGE2 was about 2.5 times more potent than 15-methyl PGE2. Volume, acid concentration, and output, and pepsin output (but not concentration) were reduced in a dose-dependent manner. In the rat, 16,16-dimethyl PGE2 also inhibited gastric secretion and prevented the formation of ulcers produced by various methods: gastric ulcers (Shay, and steroid induced) and duodenal ulcers (secretogogue induced). In this species, 1l816-dimethyl PGE2 was 2 to 50 times more potent than PGE2, depending on the endpoint, and was active orally. These prostaglandins appear to inhibit gastric acid secretion by acting directly on the parietal cells, and making these unresponsive to most stimulants. Vomiting was a side effect of the prostaglandin analogues in the dog, but almost exclusively when these were given orally. After intravenous or intrajejunal administration at doses inhibiting gastric secretion by 80%, vomiting was seen only once. These results suggest that 15-methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer.", "contents": "Gastric antisecretory and antiulcer properties of PGE2, 15-methyl PGE2, and 16, 16-dimethyl PGE2. Intravenous, oral and intrajejunal administration. 15-Methyl PGE2 and 16,16-dimethyl PGE2 were found (1) to be 40 and 100 times, respectively, more potent than PGE2 after intravenous administration in inhibiting histamine-stimulated gastric secretion in dogs with a denervated (Heidenhain) gastric pouch, (2) to be active orally and intrajejunally, whereas PGE2 was inactive, and (3) to exert antisecretory activity for longer duration than PGE2. 16,16-Dimethyl PGE2 was about 2.5 times more potent than 15-methyl PGE2. Volume, acid concentration, and output, and pepsin output (but not concentration) were reduced in a dose-dependent manner. In the rat, 16,16-dimethyl PGE2 also inhibited gastric secretion and prevented the formation of ulcers produced by various methods: gastric ulcers (Shay, and steroid induced) and duodenal ulcers (secretogogue induced). In this species, 1l816-dimethyl PGE2 was 2 to 50 times more potent than PGE2, depending on the endpoint, and was active orally. These prostaglandins appear to inhibit gastric acid secretion by acting directly on the parietal cells, and making these unresponsive to most stimulants. Vomiting was a side effect of the prostaglandin analogues in the dog, but almost exclusively when these were given orally. After intravenous or intrajejunal administration at doses inhibiting gastric secretion by 80%, vomiting was seen only once. These results suggest that 15-methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer."} {"id": "PMID:174968", "title": "Fulminant herpes simplex hepatitis in an adult: report of a case in renal transplant recipient.", "content": "A case of disseminated herpes simplex infection is reported in a 31-year-old renal transplant recipient. The patient presented with a unique clinical syndrome: high fever, severe sore throat with buccal and pharyngeal ulcerations, fulminant hepatitis, thrombocytopenia, and leukopenia. The patient died from hepatic failure, disseminated intravascular coagulopathy, and upper gastrointestinal bleeding. The diagnosis was made by positive herpes simplex virus culture from the throat, and was confirmed at autopsy by typical Cowdry's type A intranuclear inclusions in hepatocytes with positive herpes simplex virus culture from the liver. Review of the literature reveals that other reported cases have had very similar clinical findings, making disseminated herpes simplex infection with fulminant hepatitis a recognizable syndrome.", "contents": "Fulminant herpes simplex hepatitis in an adult: report of a case in renal transplant recipient. A case of disseminated herpes simplex infection is reported in a 31-year-old renal transplant recipient. The patient presented with a unique clinical syndrome: high fever, severe sore throat with buccal and pharyngeal ulcerations, fulminant hepatitis, thrombocytopenia, and leukopenia. The patient died from hepatic failure, disseminated intravascular coagulopathy, and upper gastrointestinal bleeding. The diagnosis was made by positive herpes simplex virus culture from the throat, and was confirmed at autopsy by typical Cowdry's type A intranuclear inclusions in hepatocytes with positive herpes simplex virus culture from the liver. Review of the literature reveals that other reported cases have had very similar clinical findings, making disseminated herpes simplex infection with fulminant hepatitis a recognizable syndrome."} {"id": "PMID:174969", "title": "[Seroepidemiological studies related to the association of genital herpes to cervical cancer (author's transl)].", "content": "Blood sera of 290 patients were examined for the presence of antibodies against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2): 1. lues - seronegative individuals, 2. patients with specific lues antibodies, and 3. patients with so-called carcinoma in situ and invasive carcinoma of the uterine cervix. The group of syphilis-seropositive individuals served as control for the group with cervical lesions, because in both groups certain socioepidemiologic factors (promiscuity, early sexual intercourse) appear to be prevalent. The average value for HSV-2-antibodies was significantly higher in patients with cervical lesions than that in lues-seropositive individuals. Also, the average value was higher in the lues-seropositive group than that in the lues-seronegative group. The frequency of HSV-2-antibodies was highest in the group of patients with so-called carcinoma in situ and invasive carcinoma, less in the lues-seropositive group, and even more less in the lues-seronegative group. These results make it unlikely that the connection between cervical carcinoma and HSV-2-infection is a common or \"nonsense\"-correlation. They suggest a more narrow correlation between both diseases, but leave open whether it consists of either a causal relationship between herpes infection and the development of cervical carcinoma, or a predilection for herpes infection in the cervical region by the carcinomatous tissue.", "contents": "[Seroepidemiological studies related to the association of genital herpes to cervical cancer (author's transl)]. Blood sera of 290 patients were examined for the presence of antibodies against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2): 1. lues - seronegative individuals, 2. patients with specific lues antibodies, and 3. patients with so-called carcinoma in situ and invasive carcinoma of the uterine cervix. The group of syphilis-seropositive individuals served as control for the group with cervical lesions, because in both groups certain socioepidemiologic factors (promiscuity, early sexual intercourse) appear to be prevalent. The average value for HSV-2-antibodies was significantly higher in patients with cervical lesions than that in lues-seropositive individuals. Also, the average value was higher in the lues-seropositive group than that in the lues-seronegative group. The frequency of HSV-2-antibodies was highest in the group of patients with so-called carcinoma in situ and invasive carcinoma, less in the lues-seropositive group, and even more less in the lues-seronegative group. These results make it unlikely that the connection between cervical carcinoma and HSV-2-infection is a common or \"nonsense\"-correlation. They suggest a more narrow correlation between both diseases, but leave open whether it consists of either a causal relationship between herpes infection and the development of cervical carcinoma, or a predilection for herpes infection in the cervical region by the carcinomatous tissue."} {"id": "PMID:174970", "title": "Mapping and gene conversion studies with the structural gene for iso-1-cytochrome C in yeast.", "content": "We have investigated the order of the four genes cyc1, rad7, SUP4, and cdc8 which form a tightly linked cluster on the right arm of chromosome X in the yeast Saccharomyces cerevisiae. Crossing over and coconversion data from tetrad analysis established the gene order to be centromere-cyc1-rad7-SUP4. Also cdc8 appeared to be distal to SUP4 on the basis of crossovers that were associated with conversion of SUP4. The frequencies of recombination and the occurrence of coconversions suggest that these four genes are contiguous or at least nearly so. Gene-conversion frequencies for several cyc1 alleles were studied, including cyc1-1, a deletion of the whole gene that extends into the rad7 locus. The cyc1-1 deletion was found to be capable of conversion, though at a frequency some fivefold less than the other alleles studied, and both 3:1 and 1:3 events were detected. In general 1:3 and 3:1 conversion events were equally frequent at all loci studied, and approximately 50% of conversions were accompanied by reciprocal recombination for flanking markers. The orientation of the cyc1 gene could not be clearly deduced from the behavior of the distal marker SUP4 in wild-type recombinants that arose from diploids heteroallelic for cyc1 mutations.", "contents": "Mapping and gene conversion studies with the structural gene for iso-1-cytochrome C in yeast. We have investigated the order of the four genes cyc1, rad7, SUP4, and cdc8 which form a tightly linked cluster on the right arm of chromosome X in the yeast Saccharomyces cerevisiae. Crossing over and coconversion data from tetrad analysis established the gene order to be centromere-cyc1-rad7-SUP4. Also cdc8 appeared to be distal to SUP4 on the basis of crossovers that were associated with conversion of SUP4. The frequencies of recombination and the occurrence of coconversions suggest that these four genes are contiguous or at least nearly so. Gene-conversion frequencies for several cyc1 alleles were studied, including cyc1-1, a deletion of the whole gene that extends into the rad7 locus. The cyc1-1 deletion was found to be capable of conversion, though at a frequency some fivefold less than the other alleles studied, and both 3:1 and 1:3 events were detected. In general 1:3 and 3:1 conversion events were equally frequent at all loci studied, and approximately 50% of conversions were accompanied by reciprocal recombination for flanking markers. The orientation of the cyc1 gene could not be clearly deduced from the behavior of the distal marker SUP4 in wild-type recombinants that arose from diploids heteroallelic for cyc1 mutations."} {"id": "PMID:174971", "title": "[3 new allotypes of mink blood serum alpha2-lipoproteins--Lpm 6, Lpm 7, Lpm 8].", "content": "Three new allotypes were discovered in mink sera by means of isoimmunization. Based on the results of identifications, they were referred to the Lpm system of serum alpha2-lipoprotein. They were designated as Lpm 6, Lpm 7 and Lpm 8. The allotyping of serum samples from 342 minks made possible to establish a relation between Lpm 7 and Lpm 8 using the chi2 method; it was also found that these two allotypes related to each of the first five Lpm as well as to their phenotypes, which was described earlier. There was a significant dependence of the expression of Lpm 6 on Lpm 5 indicating a genetic relation between Lpm 6 and other allotypes. The detection of Lpm 6, 7 and 8, which are the most likely under the control of the same gene (or a sustem of genes) as Lpm 1, 2, 3 and 5, is an evidence for the complex structure of the Lpm locus.", "contents": "[3 new allotypes of mink blood serum alpha2-lipoproteins--Lpm 6, Lpm 7, Lpm 8]. Three new allotypes were discovered in mink sera by means of isoimmunization. Based on the results of identifications, they were referred to the Lpm system of serum alpha2-lipoprotein. They were designated as Lpm 6, Lpm 7 and Lpm 8. The allotyping of serum samples from 342 minks made possible to establish a relation between Lpm 7 and Lpm 8 using the chi2 method; it was also found that these two allotypes related to each of the first five Lpm as well as to their phenotypes, which was described earlier. There was a significant dependence of the expression of Lpm 6 on Lpm 5 indicating a genetic relation between Lpm 6 and other allotypes. The detection of Lpm 6, 7 and 8, which are the most likely under the control of the same gene (or a sustem of genes) as Lpm 1, 2, 3 and 5, is an evidence for the complex structure of the Lpm locus."} {"id": "PMID:174977", "title": "Early stimulation of human chorionic gonadotropin secretion by dibutyryl cyclic AMP and theophylline in human malignant trophoblast cells in vitro: inhibition by actinomycin D, alpha-amanitin, and cordycepin.", "content": "Human malignant trophoblast cells (BeWo line) in culture were employed to investigate the early stimulation of human chorionic gonadotropin (hCG) secretion by 1 mM dibutyryl cyclic AMP and 1 mM theophylline (dbT). The earliest increase in secreted immunoreactive hCG occurred at 3 1/2 h following addition of dbT, and was preceded by an increase in intracellular hCG. These results suggested that dbT stimulated hCG synthesis, rather than release. Addition of either 0.062 mug/ml actinomycin D or 100 mug/ml cordycepin along with dbT, or 3 mug/ml alpha-amanitin 9 h prior to addition of dbT, prevented the increase in hCG secretion at 3 1/2-8 h. It was concluded that synthesis of RNA (possibly messenger RNA) is required for the early stimulation of hCG secretion by dbT.", "contents": "Early stimulation of human chorionic gonadotropin secretion by dibutyryl cyclic AMP and theophylline in human malignant trophoblast cells in vitro: inhibition by actinomycin D, alpha-amanitin, and cordycepin. Human malignant trophoblast cells (BeWo line) in culture were employed to investigate the early stimulation of human chorionic gonadotropin (hCG) secretion by 1 mM dibutyryl cyclic AMP and 1 mM theophylline (dbT). The earliest increase in secreted immunoreactive hCG occurred at 3 1/2 h following addition of dbT, and was preceded by an increase in intracellular hCG. These results suggested that dbT stimulated hCG synthesis, rather than release. Addition of either 0.062 mug/ml actinomycin D or 100 mug/ml cordycepin along with dbT, or 3 mug/ml alpha-amanitin 9 h prior to addition of dbT, prevented the increase in hCG secretion at 3 1/2-8 h. It was concluded that synthesis of RNA (possibly messenger RNA) is required for the early stimulation of hCG secretion by dbT."} {"id": "PMID:174978", "title": "[The diagnosis of carcinoma of the breast in relation to growth rate (author's transl)].", "content": "The doubling time (DT) was estimated quantitatively for 16 carcinomas of the breast according to the method described by Collins and co-workers in 1956. This is based on the concept of constant and exponential growth. Observation interval for these mammographically confirmed tumors was between 83 and 1,034 days. The DT was calculated to vary from 45 to 260 days; in order to reach a diameter of 1 cm. after 30 divisions would require a period of 3.7 to 21.4 years. Mammography frequently demonstrates small, clinically occult, tumours. Axillary lymph node metastases are relatively rare from small tumours; growth rate of 70% of breast carcinomas in such that an annual clinical and radiological check-up will prove to be the best means of reducing mortality from carcinoma of the breast. The risk inherent in the radiation resulting from annual mammography is acceptable in women over 35 years. This leaves the problem of rapidly growing carcinomas which would escape early diagnosis by early examinations. Half-yearly examinations of women in high risk groups (1. Previous mastectomy for carcinoma, 2. Biopsy-proven mastopathy with atypical proliferation) comprising about 30% of carcinomas with a short doubling time would appear to be reasonable.", "contents": "[The diagnosis of carcinoma of the breast in relation to growth rate (author's transl)]. The doubling time (DT) was estimated quantitatively for 16 carcinomas of the breast according to the method described by Collins and co-workers in 1956. This is based on the concept of constant and exponential growth. Observation interval for these mammographically confirmed tumors was between 83 and 1,034 days. The DT was calculated to vary from 45 to 260 days; in order to reach a diameter of 1 cm. after 30 divisions would require a period of 3.7 to 21.4 years. Mammography frequently demonstrates small, clinically occult, tumours. Axillary lymph node metastases are relatively rare from small tumours; growth rate of 70% of breast carcinomas in such that an annual clinical and radiological check-up will prove to be the best means of reducing mortality from carcinoma of the breast. The risk inherent in the radiation resulting from annual mammography is acceptable in women over 35 years. This leaves the problem of rapidly growing carcinomas which would escape early diagnosis by early examinations. Half-yearly examinations of women in high risk groups (1. Previous mastectomy for carcinoma, 2. Biopsy-proven mastopathy with atypical proliferation) comprising about 30% of carcinomas with a short doubling time would appear to be reasonable."} {"id": "PMID:174979", "title": "[A comparison of radiology and scanning with 99mTc-pyrophosphate in 125 patients with tumours (author's transl)].", "content": "Various portions of the skeleton were examined in 125 patients both radiologically and by scanning, using 99mTc-pyrophosphate. The results are compared, particular attention being paid to errors in diagnosis. The figures show that scans represent a valuable additional form of examination for detecting tumours which have not been found radiologically. The importance of serial observations is discussed.", "contents": "[A comparison of radiology and scanning with 99mTc-pyrophosphate in 125 patients with tumours (author's transl)]. Various portions of the skeleton were examined in 125 patients both radiologically and by scanning, using 99mTc-pyrophosphate. The results are compared, particular attention being paid to errors in diagnosis. The figures show that scans represent a valuable additional form of examination for detecting tumours which have not been found radiologically. The importance of serial observations is discussed."} {"id": "PMID:174980", "title": "[The distribution of Sn2+ after application as a complex (author's transl)].", "content": "On animal experiments was shown that Sn2+ after i.v. application with 113Sn as radioactiv indicator was deposited in the skeleton. Experiments were done with citrat-, tartrat-, pyrophosphat-, phosphat- and Sn2+/HCl-complexes. The importance of the results for the use of Sn2+-solutions in Nuclear Medicine for men are discussed.", "contents": "[The distribution of Sn2+ after application as a complex (author's transl)]. On animal experiments was shown that Sn2+ after i.v. application with 113Sn as radioactiv indicator was deposited in the skeleton. Experiments were done with citrat-, tartrat-, pyrophosphat-, phosphat- and Sn2+/HCl-complexes. The importance of the results for the use of Sn2+-solutions in Nuclear Medicine for men are discussed."} {"id": "PMID:174981", "title": "[Klippel-Trenaunay's syndrome (author's transl)].", "content": "The authors have observed seven cases of this syndrome, and together with a review of the literature, they discuss the various facets which constitute this disease. Particular attention is paid to the findings in the vessels of the extremities on phlebography and arteriography, and the authors conclude that these examinations are vital in the diagnosis of this syndrome.", "contents": "[Klippel-Trenaunay's syndrome (author's transl)]. The authors have observed seven cases of this syndrome, and together with a review of the literature, they discuss the various facets which constitute this disease. Particular attention is paid to the findings in the vessels of the extremities on phlebography and arteriography, and the authors conclude that these examinations are vital in the diagnosis of this syndrome."} {"id": "PMID:174984", "title": "[Stretched veins, a new, indirect sign of malignant breast tumours (author's transl)].", "content": "The diagnosis of malignant breast tumours depends on direct and indirect radiological signs. Amongst the latter, considerable emphasis has been placed in the literature on the finding of dilated veins. An analysis of the literature and of nearly 1,500 examinations has shown, however that this sign is not as reliable as has been thought. A new sign has been noticed, which has so far not been emphasised in the literature. This is stretching of the veins. It is not a direct sign, but as an indirect sign it is a more reliable indication of malignancy than dilatation of veins. Stretching of veins may also occur in benign conditions, but it is twice as frequent in the presence of malignant tumours. It is therefore considered that the presence of stretched veins is an indirect sign of malignant breast tumours.", "contents": "[Stretched veins, a new, indirect sign of malignant breast tumours (author's transl)]. The diagnosis of malignant breast tumours depends on direct and indirect radiological signs. Amongst the latter, considerable emphasis has been placed in the literature on the finding of dilated veins. An analysis of the literature and of nearly 1,500 examinations has shown, however that this sign is not as reliable as has been thought. A new sign has been noticed, which has so far not been emphasised in the literature. This is stretching of the veins. It is not a direct sign, but as an indirect sign it is a more reliable indication of malignancy than dilatation of veins. Stretching of veins may also occur in benign conditions, but it is twice as frequent in the presence of malignant tumours. It is therefore considered that the presence of stretched veins is an indirect sign of malignant breast tumours."} {"id": "PMID:174988", "title": "[Spread of acute haemorrhagic conjunctivitis virus in virgin soil (Hokkaido, Japan): observation with serological surveys (author's transl)].", "content": "Acute haemorrhagic conjunctivitis (AHC), a novel disease caused with a new type of enterovirus, occurred for the first time in Sapporo City and other areas of Hokkaido in October of 1971. During first 4 months, 1,000 or more cases of AHC were reported in Sapporo and 2,300 cases in other areas. Thereafter, there are no epidemic of AHC in any areas, though there are sporadic cases up to date. To know the spread of exogenous agent, AHC virus, in Hokkaido, the neutralizing antibody was measured with sera of healthy adults resident in 12 separated districts of Hokkaido in 1973 and 1974. It was revealed that the positive reactors to AHC virus were found in 5 to 35% in all districts but one in 1974, and AHC virus was distributed in almost all the areas of Hokkaido within a period of two and half years after invasion. In addition, a sequential sero-survey to detect the spread of AHC virus has been carried out in Sapporo. A rate of neutralizing antibody positives in healthy adults did not show a clear increase on sera withdrawn one year after epidemic of AHC in comparison with those before epidemic, but show a remarkable increase on sera withdrawn later in spite of non-epidemic. An increase of antibody positive rate in non-epidemic period was also obtained from sera of healthy adults resident in districts other than Sapporo. These findings made doubt the changes in transmission on mode and/or in clinical pictures, and the viral mutation in biological character, such as temperature for propagation, may be supposed.", "contents": "[Spread of acute haemorrhagic conjunctivitis virus in virgin soil (Hokkaido, Japan): observation with serological surveys (author's transl)]. Acute haemorrhagic conjunctivitis (AHC), a novel disease caused with a new type of enterovirus, occurred for the first time in Sapporo City and other areas of Hokkaido in October of 1971. During first 4 months, 1,000 or more cases of AHC were reported in Sapporo and 2,300 cases in other areas. Thereafter, there are no epidemic of AHC in any areas, though there are sporadic cases up to date. To know the spread of exogenous agent, AHC virus, in Hokkaido, the neutralizing antibody was measured with sera of healthy adults resident in 12 separated districts of Hokkaido in 1973 and 1974. It was revealed that the positive reactors to AHC virus were found in 5 to 35% in all districts but one in 1974, and AHC virus was distributed in almost all the areas of Hokkaido within a period of two and half years after invasion. In addition, a sequential sero-survey to detect the spread of AHC virus has been carried out in Sapporo. A rate of neutralizing antibody positives in healthy adults did not show a clear increase on sera withdrawn one year after epidemic of AHC in comparison with those before epidemic, but show a remarkable increase on sera withdrawn later in spite of non-epidemic. An increase of antibody positive rate in non-epidemic period was also obtained from sera of healthy adults resident in districts other than Sapporo. These findings made doubt the changes in transmission on mode and/or in clinical pictures, and the viral mutation in biological character, such as temperature for propagation, may be supposed."} {"id": "PMID:174989", "title": "The plasmatic 11-hydroxy-corticosteroid response in the human to a synthetic octadecapeptide corticotrophin (C-41795-Ba).", "content": "The adrenal response as measured by the plasmatic changes in 11-hydroxy-corticosteroid (11-OHCS) concentration following the administration of a synthetic octadecapeptide (C-41795-Ba) was compared in 17 normal young males with that obtained with the commercially available tetracosactrin. C-41795-Ba polypeptide shows a higher potency than tetracosactrin. Its effects are longer lasting when administered intravenously which indicates a significant local inactivation of the polypeptide.", "contents": "The plasmatic 11-hydroxy-corticosteroid response in the human to a synthetic octadecapeptide corticotrophin (C-41795-Ba). The adrenal response as measured by the plasmatic changes in 11-hydroxy-corticosteroid (11-OHCS) concentration following the administration of a synthetic octadecapeptide (C-41795-Ba) was compared in 17 normal young males with that obtained with the commercially available tetracosactrin. C-41795-Ba polypeptide shows a higher potency than tetracosactrin. Its effects are longer lasting when administered intravenously which indicates a significant local inactivation of the polypeptide."} {"id": "PMID:174990", "title": "Binding of somatomedins and insulin to plasma membranes prepared from rat and monkey tissue.", "content": "Particulate membranes prepared from a variety of monkey and rat tissues were shown to have specific binding sites for somatomedin A. Binding to talc on the other hand showed no specificity, and the sensitivity was less. The membrane-bound somatomedin A was displaced by somatomedin A in concentrations between 0.01 and 5 U/ml. Of the other hormones tested only insulin in high concentrations could interfere with the binding of labelled somatomedin A to tissue membranes. Membranes prepared from a number of rat and monkey tissues also contained binding sites for insulin. Somatomedin A could interfere with the binding of labelled insulin. No binding was observed for somatomedin B in the tissues studied.", "contents": "Binding of somatomedins and insulin to plasma membranes prepared from rat and monkey tissue. Particulate membranes prepared from a variety of monkey and rat tissues were shown to have specific binding sites for somatomedin A. Binding to talc on the other hand showed no specificity, and the sensitivity was less. The membrane-bound somatomedin A was displaced by somatomedin A in concentrations between 0.01 and 5 U/ml. Of the other hormones tested only insulin in high concentrations could interfere with the binding of labelled somatomedin A to tissue membranes. Membranes prepared from a number of rat and monkey tissues also contained binding sites for insulin. Somatomedin A could interfere with the binding of labelled insulin. No binding was observed for somatomedin B in the tissues studied."} {"id": "PMID:174991", "title": "Impairment and restoration of response to TSH in dog thyroid slices after treatment with phospholipase A and lubrol PX.", "content": "Incubation of dog thyroid slices with phospholipase A (10-40 U/Ml) or Lubrol PX (0.08-0.4%) caused a diminution in the subsequent TSH effect on the tissue cyclic AMP level and glucose oxidation. The same treatment had no effect on the basal level of these parameters. When the phospholipase A or Lubrol PX-treated slices were rinsed intensively with a Krebs-Ringer bicarbonate buffer and then incubated at 37degreesC in the same buffer for a further 1 to 3 hours, responsiveness to TSH recovered progressively reaching almost completely that of the control slices. Again, these procedures were without any significant effect on the responsiveness of the control slices. The above results together with those reported previously suggest strongly that phospholipids are an essential component of the plasma membrane system by which TSH stimulates adenylate cyclase activity. In addition, these essential lipids in the membrane appear to be renewed rather efficiently in this tissue, thus securing the functional integrity of the thyroid in the face of various deleterious situations.", "contents": "Impairment and restoration of response to TSH in dog thyroid slices after treatment with phospholipase A and lubrol PX. Incubation of dog thyroid slices with phospholipase A (10-40 U/Ml) or Lubrol PX (0.08-0.4%) caused a diminution in the subsequent TSH effect on the tissue cyclic AMP level and glucose oxidation. The same treatment had no effect on the basal level of these parameters. When the phospholipase A or Lubrol PX-treated slices were rinsed intensively with a Krebs-Ringer bicarbonate buffer and then incubated at 37degreesC in the same buffer for a further 1 to 3 hours, responsiveness to TSH recovered progressively reaching almost completely that of the control slices. Again, these procedures were without any significant effect on the responsiveness of the control slices. The above results together with those reported previously suggest strongly that phospholipids are an essential component of the plasma membrane system by which TSH stimulates adenylate cyclase activity. In addition, these essential lipids in the membrane appear to be renewed rather efficiently in this tissue, thus securing the functional integrity of the thyroid in the face of various deleterious situations."} {"id": "PMID:174992", "title": "The effect of ACTH administration on the phagocytic and bactericidal activities of human polymorphonuclear leukocytes.", "content": "Metabolic and bactericial activities of leukocytes obtained from 5 normal volunteers receiving 1 mg of synthetic B1-24 ACTH intra-muscularly daily for 7 days, were studied. Bactericidal activity and phagocytosis induced hexosemonophosphate shunt activity of leukocytes were found to be depressed following ACTH administration. However, glycolytic activity, which provides the necessary energy for particle uptake by leukocytes, was not altered. These findings indicate that a moderately prolonged exposure to elevated levels of plasma cortisol does not affect the phagocytic activity of leukocytes (as indicated by glycolytic activity) but significantly impairs their ability to destroy the ingested bacteria. It is suggested that the impaired bactericidal activity of leukocytes reported in children suffering from protein-calorie malnutrition may partly be due to elevated plasma cortisol levels seen in them.", "contents": "The effect of ACTH administration on the phagocytic and bactericidal activities of human polymorphonuclear leukocytes. Metabolic and bactericial activities of leukocytes obtained from 5 normal volunteers receiving 1 mg of synthetic B1-24 ACTH intra-muscularly daily for 7 days, were studied. Bactericidal activity and phagocytosis induced hexosemonophosphate shunt activity of leukocytes were found to be depressed following ACTH administration. However, glycolytic activity, which provides the necessary energy for particle uptake by leukocytes, was not altered. These findings indicate that a moderately prolonged exposure to elevated levels of plasma cortisol does not affect the phagocytic activity of leukocytes (as indicated by glycolytic activity) but significantly impairs their ability to destroy the ingested bacteria. It is suggested that the impaired bactericidal activity of leukocytes reported in children suffering from protein-calorie malnutrition may partly be due to elevated plasma cortisol levels seen in them."} {"id": "PMID:174994", "title": "Synthesis of 9-O-acetyl- and 4,9-di-O-acetyl derivatives of the methyl ester of N-acetyl-beta-D-neuraminic acid methylglycoside. Their use as models in periodate oxidation studies.", "content": "Reaction of the methyl ester of N-acetyl-beta-D-neuraminic acid methyl glycoside with N-acetylimidazole yielded the corresponding 9-O-acetyl- and 4,9-di-O-acetyl derivatives. The structures of these compounds were confirmed by mass spectrometry and both 1H and 13C NMR spectroscopy. The compounds served as model substances in a comparative study of the rate of periodate oxidation of unsubstituted and of 9-O-acetylated-N-acetyl-neuraminic acids. This reaction was strongly hampered by the presence of the 9-O-acetyl group. The low molar absorbancy coefficient of N-acetyl-9-O-acetylneuraminic acid in the periodic acid/thiobarbituric acid assay can be explained by this retardation.", "contents": "Synthesis of 9-O-acetyl- and 4,9-di-O-acetyl derivatives of the methyl ester of N-acetyl-beta-D-neuraminic acid methylglycoside. Their use as models in periodate oxidation studies. Reaction of the methyl ester of N-acetyl-beta-D-neuraminic acid methyl glycoside with N-acetylimidazole yielded the corresponding 9-O-acetyl- and 4,9-di-O-acetyl derivatives. The structures of these compounds were confirmed by mass spectrometry and both 1H and 13C NMR spectroscopy. The compounds served as model substances in a comparative study of the rate of periodate oxidation of unsubstituted and of 9-O-acetylated-N-acetyl-neuraminic acids. This reaction was strongly hampered by the presence of the 9-O-acetyl group. The low molar absorbancy coefficient of N-acetyl-9-O-acetylneuraminic acid in the periodic acid/thiobarbituric acid assay can be explained by this retardation."} {"id": "PMID:174995", "title": "Quantitative determination of poly(adenosine diphosphate ribose) in different hepatic tissues by an isotope dilution procedure.", "content": "A procedure has been developed for the quantitation of poly(ADP-ribose) in intact tissues. It is based on the dilution of added [3H]poly(ADP-ribose) by the endogenous polymer. 5 - 6 nanomoles protein-bound ADP-ribose per mg DNA were found in adult and neonatal rat liver, while Zajdela hepatoma cells had significantly lower values. A comparison with mono(ADP-ribose) residues in adult rat liver revealed similar levels of monomeric and polymeric ADP-ribose residues. This means that far more proteins (or acceptor sites on proteins) must be occupied by single ADP-ribose residues than by oligo or poly(ADP-ribose) chains. While the poly(ADP-ribose) levels of the different tissues do not correlate with the corresponding proliferation rates, the amount of mono(ADP-ribose) does show a certain Correlation, being low in rapidly growing tissues.", "contents": "Quantitative determination of poly(adenosine diphosphate ribose) in different hepatic tissues by an isotope dilution procedure. A procedure has been developed for the quantitation of poly(ADP-ribose) in intact tissues. It is based on the dilution of added [3H]poly(ADP-ribose) by the endogenous polymer. 5 - 6 nanomoles protein-bound ADP-ribose per mg DNA were found in adult and neonatal rat liver, while Zajdela hepatoma cells had significantly lower values. A comparison with mono(ADP-ribose) residues in adult rat liver revealed similar levels of monomeric and polymeric ADP-ribose residues. This means that far more proteins (or acceptor sites on proteins) must be occupied by single ADP-ribose residues than by oligo or poly(ADP-ribose) chains. While the poly(ADP-ribose) levels of the different tissues do not correlate with the corresponding proliferation rates, the amount of mono(ADP-ribose) does show a certain Correlation, being low in rapidly growing tissues."} {"id": "PMID:174996", "title": "Isoenzymes of serum N-acetyl-beta-D-glucosaminidase in the I cell disease heterozygote.", "content": "Serum N-acetyl-beta-D-hexosaminidase is compared quantitatively and qualitatively in 14 obligate heterozygotes for the mutant gene causing I cell disease (ICD) or mucolipidosis II and in 31 normal controls. The average specific activity in either group is significantly different but reliable heterozygote detection cannot be achieved because of some overlapping of the ranges of individual results. Fractionation of the enzyme either by DEAE cellulose column chromatography, or by heat inactivation, yields a typical average result for each genotype. Also, mere expression of the various components as percentages of the total activity is not useful for certain identification of the ICD heterozygote. There is considerable overlapping of the percents hexosaminidase I1 and A in both groups of sera. If enzymatic hydrolysis by any component is expressed as a partial activity, a much better though not absolute distinction between the ICD heterozygote and the normal control becomes possible. Only the latter way of expression of hexosaminidase results makes distinction between the ICD heterozygote and the Tay-Sachs heterozygote very probable.", "contents": "Isoenzymes of serum N-acetyl-beta-D-glucosaminidase in the I cell disease heterozygote. Serum N-acetyl-beta-D-hexosaminidase is compared quantitatively and qualitatively in 14 obligate heterozygotes for the mutant gene causing I cell disease (ICD) or mucolipidosis II and in 31 normal controls. The average specific activity in either group is significantly different but reliable heterozygote detection cannot be achieved because of some overlapping of the ranges of individual results. Fractionation of the enzyme either by DEAE cellulose column chromatography, or by heat inactivation, yields a typical average result for each genotype. Also, mere expression of the various components as percentages of the total activity is not useful for certain identification of the ICD heterozygote. There is considerable overlapping of the percents hexosaminidase I1 and A in both groups of sera. If enzymatic hydrolysis by any component is expressed as a partial activity, a much better though not absolute distinction between the ICD heterozygote and the normal control becomes possible. Only the latter way of expression of hexosaminidase results makes distinction between the ICD heterozygote and the Tay-Sachs heterozygote very probable."} {"id": "PMID:174997", "title": "Carcinoma of the esophagus in Africans: establishment of a continuously growing cell line from a tumor specimen.", "content": "Biopsy material, from a patient with an esophageal carcinoma of a type occurring relatively frequently in Africans in some regions of Southern Africa, has been adapted to cell culture conditions and has developed into a continuously growing tumor cell line. The cells have a squamous pattern of growth which they maintain, without piling up, even in heavily confluent cultures.", "contents": "Carcinoma of the esophagus in Africans: establishment of a continuously growing cell line from a tumor specimen. Biopsy material, from a patient with an esophageal carcinoma of a type occurring relatively frequently in Africans in some regions of Southern Africa, has been adapted to cell culture conditions and has developed into a continuously growing tumor cell line. The cells have a squamous pattern of growth which they maintain, without piling up, even in heavily confluent cultures."} {"id": "PMID:175013", "title": "Identification of cholesterol in the receptor site for rickettsiae on sheep erythrocyte membranes.", "content": "Cholesterol was identified as an essential component of the receptor on the sheep erythrocyte to which Rickettsia prowazeki adsorbs before lysing the cell. Erythrocytes or ghosts, derived by hypotonic lysis, were treated with proteolytic enzymes, sialidase, sulfhydryl reagents, and periodate without affecting their ability to adsorb rickettsiae. Lipid extracts of ghosts and erythrocytes, on the other hand, contained receptor activity. Fractionation of the lipid extracts by silicic acid column chromatogrphy resulted in the isolation of receptor activity in a neutral lipid fraction. The lipid fractions demonstrated receptor acitity at 34 C but not at 0 C. These properties are also characteristic of the receptor activity with erythrocytes and ghosts. Cholesterol, co-lyophilized with palmitic acid, was found to possess receptor activity. Palmitic acid alone, cholesterol-lecithin, cholestane-palmitic acid, and various phospholipids and glycolipids had no receptor activity. Ghosts treated with amphotericin B or digitonin, compounds that bind to cholesterol in the membrane, lost their ability to adsorb rickettsiae.", "contents": "Identification of cholesterol in the receptor site for rickettsiae on sheep erythrocyte membranes. Cholesterol was identified as an essential component of the receptor on the sheep erythrocyte to which Rickettsia prowazeki adsorbs before lysing the cell. Erythrocytes or ghosts, derived by hypotonic lysis, were treated with proteolytic enzymes, sialidase, sulfhydryl reagents, and periodate without affecting their ability to adsorb rickettsiae. Lipid extracts of ghosts and erythrocytes, on the other hand, contained receptor activity. Fractionation of the lipid extracts by silicic acid column chromatogrphy resulted in the isolation of receptor activity in a neutral lipid fraction. The lipid fractions demonstrated receptor acitity at 34 C but not at 0 C. These properties are also characteristic of the receptor activity with erythrocytes and ghosts. Cholesterol, co-lyophilized with palmitic acid, was found to possess receptor activity. Palmitic acid alone, cholesterol-lecithin, cholestane-palmitic acid, and various phospholipids and glycolipids had no receptor activity. Ghosts treated with amphotericin B or digitonin, compounds that bind to cholesterol in the membrane, lost their ability to adsorb rickettsiae."} {"id": "PMID:175014", "title": "Role of Ca2+ and Mg2+ in some human neutrophil functions as indicated by ionophore A23187.", "content": "Studies with the divalent cation ionophore A23187 suggest that both Ca2+ and Mg2+ ion influx play a role in human peripheral blood neutrophil function. Degranulation of neutrophils occurred at ionophore concentrations of 10(-5) M and was Ca2+ but not Mg2+ dependent. Modulation of neutrophil chemotaxis was enhanced optimally by 10(-7) M ionophore and was both Ca2+ and Mg2+ dependent. Concentrations of ionophore as low as 10(-12) M seemed to sensitize the cells to a concentration of phorbol myristate acetate which by itself was not chemotactic. These findings also indicate that factors other than Ca2+ or increases in cyclic nucleotides are important to initiation and modulation of neutrophil function.", "contents": "Role of Ca2+ and Mg2+ in some human neutrophil functions as indicated by ionophore A23187. Studies with the divalent cation ionophore A23187 suggest that both Ca2+ and Mg2+ ion influx play a role in human peripheral blood neutrophil function. Degranulation of neutrophils occurred at ionophore concentrations of 10(-5) M and was Ca2+ but not Mg2+ dependent. Modulation of neutrophil chemotaxis was enhanced optimally by 10(-7) M ionophore and was both Ca2+ and Mg2+ dependent. Concentrations of ionophore as low as 10(-12) M seemed to sensitize the cells to a concentration of phorbol myristate acetate which by itself was not chemotactic. These findings also indicate that factors other than Ca2+ or increases in cyclic nucleotides are important to initiation and modulation of neutrophil function."} {"id": "PMID:175015", "title": "Increased cyclic adenosine 3',5'-monophosphate content in guinea pig ileum after exposure to Staphylococcus aureus delta-toxin.", "content": "To compare Staphylococcus aureus delta-toxin with cholera toxin, which is known to increase cellular cyclic adenosine 3',5'-monophosphate (cAMP), studies were undertaken to determine the effect of delta-toxin on the cAMP content of guinea pig ileum maintained in vitro. Concentrations of delta-toxin as low as 0.40 mug/ml increased cAMP levels in guinea pig ileum after 2 h of incubation. Histological damage was seen in ileum exposed for 2 h to delta-toxin concentrations of 100 mug/ml. As little as 3 mug of delta-toxin increased vascular permeability in guinea pig skin. Permeability changes became evident within 5 min and were maximal within 6 h, whereas those produced by cholera toxin required 24 h to become maximal. Benadryl did not interfere with the ability of these toxins to alter vascular permeability. Purified egg lecithin reduced the effectiveness of delta-toxin in the skin but did not inhibit cholera toxin. Delta-toxin in concentrations as low as 0.1 mug/ml caused dislodgement of HeLa cells in tissue cultures. Therefore, delta-toxin appears unique in being the only bacterial toxin, currently known to alter water absorption in the ileum, that is capable of both increasing cAMP levels and being cytotoxic. These findings suggest a possible role for delta-toxin in the pathogenesis of staphylococcal enteritis.", "contents": "Increased cyclic adenosine 3',5'-monophosphate content in guinea pig ileum after exposure to Staphylococcus aureus delta-toxin. To compare Staphylococcus aureus delta-toxin with cholera toxin, which is known to increase cellular cyclic adenosine 3',5'-monophosphate (cAMP), studies were undertaken to determine the effect of delta-toxin on the cAMP content of guinea pig ileum maintained in vitro. Concentrations of delta-toxin as low as 0.40 mug/ml increased cAMP levels in guinea pig ileum after 2 h of incubation. Histological damage was seen in ileum exposed for 2 h to delta-toxin concentrations of 100 mug/ml. As little as 3 mug of delta-toxin increased vascular permeability in guinea pig skin. Permeability changes became evident within 5 min and were maximal within 6 h, whereas those produced by cholera toxin required 24 h to become maximal. Benadryl did not interfere with the ability of these toxins to alter vascular permeability. Purified egg lecithin reduced the effectiveness of delta-toxin in the skin but did not inhibit cholera toxin. Delta-toxin in concentrations as low as 0.1 mug/ml caused dislodgement of HeLa cells in tissue cultures. Therefore, delta-toxin appears unique in being the only bacterial toxin, currently known to alter water absorption in the ileum, that is capable of both increasing cAMP levels and being cytotoxic. These findings suggest a possible role for delta-toxin in the pathogenesis of staphylococcal enteritis."} {"id": "PMID:175016", "title": "Variability in the structural polypeptides of herpes simplex virus 1 strains: potential application in molecular epidemiology.", "content": "This paper reports on the variability of structural polypeptides of 53 strains of herpes simplex virus 1 isolated from Italy, Uganda, South Africa, and various locations in the United States. Most strains were passaged a limited number of times at low multiplicity outside the human host; a few strains were characterized by numberous passages at variable multiplicities in cell culture and experimental animals. The acrylamide gel electrophoresis of polypeptides from purified virions revealed seven variable polypeptides. Virion polypeptides (VP) 7, 11, 13, 14, 15.2 and 23 were present in at least two isotypic forms characterized by fast and slow electrophoretic mobilities. VP8 could not be detected in three strains. In addition, VP13, 15.2, and 23 in some strains were either absent or comigrated with other polypeptides. A variety of tests showed that the variability in electrophoretic mobility of polypeptides was reproducible and could not be attributed to artifacts of purification, solubilization, or electrophoresis. Attempts to classify the strains on the basis of electrophoretic mobility of five or all seven variable polypeptides yielded 14 and 19 groups, respectively. The bulk of the strains (41 to 53) fell into six groups. Not all possible permutations of variable polypeptides were observed. Comparison of early and late passages of laboratory strains showed that in the few instances tested the variability could not be attributed to the propagation of the virus outside the human host. Clustering of strains on the basis of country of origin was not observed. Some clustering of isolates on the basis of site of isolation was observed, and the data do suggest that further analyses of isolates for evidence of a correlation between the site of localization on the human body and the structural polypeptides might be useful. Electrophoretic characterization of structural polypeptides has the potential of becoming a powerful tool for epidemiological studies of herpes simplex virus infections.", "contents": "Variability in the structural polypeptides of herpes simplex virus 1 strains: potential application in molecular epidemiology. This paper reports on the variability of structural polypeptides of 53 strains of herpes simplex virus 1 isolated from Italy, Uganda, South Africa, and various locations in the United States. Most strains were passaged a limited number of times at low multiplicity outside the human host; a few strains were characterized by numberous passages at variable multiplicities in cell culture and experimental animals. The acrylamide gel electrophoresis of polypeptides from purified virions revealed seven variable polypeptides. Virion polypeptides (VP) 7, 11, 13, 14, 15.2 and 23 were present in at least two isotypic forms characterized by fast and slow electrophoretic mobilities. VP8 could not be detected in three strains. In addition, VP13, 15.2, and 23 in some strains were either absent or comigrated with other polypeptides. A variety of tests showed that the variability in electrophoretic mobility of polypeptides was reproducible and could not be attributed to artifacts of purification, solubilization, or electrophoresis. Attempts to classify the strains on the basis of electrophoretic mobility of five or all seven variable polypeptides yielded 14 and 19 groups, respectively. The bulk of the strains (41 to 53) fell into six groups. Not all possible permutations of variable polypeptides were observed. Comparison of early and late passages of laboratory strains showed that in the few instances tested the variability could not be attributed to the propagation of the virus outside the human host. Clustering of strains on the basis of country of origin was not observed. Some clustering of isolates on the basis of site of isolation was observed, and the data do suggest that further analyses of isolates for evidence of a correlation between the site of localization on the human body and the structural polypeptides might be useful. Electrophoretic characterization of structural polypeptides has the potential of becoming a powerful tool for epidemiological studies of herpes simplex virus infections."} {"id": "PMID:175017", "title": "Characteristics of cells present in peritoneal fluids of mice injected intraperitoneally with Bordetella pertussis.", "content": "Peritoneal fluids obtained from mice after the intraperitoneal administration of Bordetella pertussis vaccine, heated vaccine, an extract of the organisms, killed Escherichia coli, or thioglycolate medium were examined in terms of total cells and percentage that adhered to glass cover slips during 2-h incubation period. All these substances were found to increase the number of leukocytes in peritoneal fluid within 1 to 2 days after the injection. This increase appeared to be due to an influx of macrophages and polymorphonuclear leukocytes with relative proportions at a given time dependent upon the material involved in the induction of the response. The initial increases after pertussis vaccine seemed to be due mainly to an influx of monomuclear cells, whereas with E. coli neutrophils constituted the major portion of the cell population. The percentage of peritoneal cells that attached to glass was also found to be markedly reduced in preparations obtained from mice after the injection of B. pertussis or E. coli. There appeared to be differences in persistence of this phenomenon, with preparations containing the histamine-sensitizing factor being the most active in affecting adherence properties. Thus these data would suggest that the action of B. pertussis on macrophages (or precursors) and neutrophils is not expressed in terms of suppression of emigration properties, as has been reported by others for lymphocytes, but is manifested in the alteration of glass-adherence characteristics. Within experimental limitations, it is believed that macrophages are possibly more involved in terms of altered function than are the polymorphonuclear cells.", "contents": "Characteristics of cells present in peritoneal fluids of mice injected intraperitoneally with Bordetella pertussis. Peritoneal fluids obtained from mice after the intraperitoneal administration of Bordetella pertussis vaccine, heated vaccine, an extract of the organisms, killed Escherichia coli, or thioglycolate medium were examined in terms of total cells and percentage that adhered to glass cover slips during 2-h incubation period. All these substances were found to increase the number of leukocytes in peritoneal fluid within 1 to 2 days after the injection. This increase appeared to be due to an influx of macrophages and polymorphonuclear leukocytes with relative proportions at a given time dependent upon the material involved in the induction of the response. The initial increases after pertussis vaccine seemed to be due mainly to an influx of monomuclear cells, whereas with E. coli neutrophils constituted the major portion of the cell population. The percentage of peritoneal cells that attached to glass was also found to be markedly reduced in preparations obtained from mice after the injection of B. pertussis or E. coli. There appeared to be differences in persistence of this phenomenon, with preparations containing the histamine-sensitizing factor being the most active in affecting adherence properties. Thus these data would suggest that the action of B. pertussis on macrophages (or precursors) and neutrophils is not expressed in terms of suppression of emigration properties, as has been reported by others for lymphocytes, but is manifested in the alteration of glass-adherence characteristics. Within experimental limitations, it is believed that macrophages are possibly more involved in terms of altered function than are the polymorphonuclear cells."} {"id": "PMID:175018", "title": "Effect of in vitro adaptation of Marek's disease virus on pock induction on the chorioallantoic membrane of embryonated chicken eggs.", "content": "Cell-associated preparations of several isolates of Marek's disease virus produced more pocks on the chorioallantoic membrane of embryonated chicken eggs than plaques in duck embryo fibroblasts, thus indicating that lesion response in eggs was more sensitive than cytopathic response in duck embryo fibroblasts for assaying low-passage Marek's disease virus. Adaptation of the virus to cell cultures by serial passages, however, substantially reduced its pock response so that the titer ratio (plaque-forming units in duck embryo fibroblasts/pock-forming units in eggs) of cell culture-adapted Marek's disease virus was 1 or higher. The decreased pock response could not be attributed to selection of preexisting virus variant(s) with low affinity for chorioallantoic membrane because cloned Marek's disease virus had a good pock response at low cell culture passage levels, but this response decreased as the virus was attenuated by serial cell culture passage.", "contents": "Effect of in vitro adaptation of Marek's disease virus on pock induction on the chorioallantoic membrane of embryonated chicken eggs. Cell-associated preparations of several isolates of Marek's disease virus produced more pocks on the chorioallantoic membrane of embryonated chicken eggs than plaques in duck embryo fibroblasts, thus indicating that lesion response in eggs was more sensitive than cytopathic response in duck embryo fibroblasts for assaying low-passage Marek's disease virus. Adaptation of the virus to cell cultures by serial passages, however, substantially reduced its pock response so that the titer ratio (plaque-forming units in duck embryo fibroblasts/pock-forming units in eggs) of cell culture-adapted Marek's disease virus was 1 or higher. The decreased pock response could not be attributed to selection of preexisting virus variant(s) with low affinity for chorioallantoic membrane because cloned Marek's disease virus had a good pock response at low cell culture passage levels, but this response decreased as the virus was attenuated by serial cell culture passage."} {"id": "PMID:175019", "title": "Inhibition of lipopolysaccharide-initiated activation of serum complement by polymyxin B.", "content": "Treatment of bacterial lipopolysaccharides (endotoxins) isolated from Salmonella minnesota R595 or purified lipid A with the antibiotic polymyxin B has been demonstrated to abrogate the ability of these molecules to activate serum complement. The inhibition is a function of the ratio of polymyxin B to lipopolysaccharide.", "contents": "Inhibition of lipopolysaccharide-initiated activation of serum complement by polymyxin B. Treatment of bacterial lipopolysaccharides (endotoxins) isolated from Salmonella minnesota R595 or purified lipid A with the antibiotic polymyxin B has been demonstrated to abrogate the ability of these molecules to activate serum complement. The inhibition is a function of the ratio of polymyxin B to lipopolysaccharide."} {"id": "PMID:175020", "title": "Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma.", "content": "Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV-induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV-specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2-6 years after initial therapy had only low levels of EBV-specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA-specific IgA and even fewer EA-specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA- or D-specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV-specific antibodies. Possible reasons for this unique response in NPC have been discussed.", "contents": "Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV-induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV-specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2-6 years after initial therapy had only low levels of EBV-specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA-specific IgA and even fewer EA-specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA- or D-specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV-specific antibodies. Possible reasons for this unique response in NPC have been discussed."} {"id": "PMID:175021", "title": "Inhibition of cell-mediated cytotoxicity to chemically induced rat tumours by soluble tumour and embryo cell extracts.", "content": "When lymph-node and spleen cells from rats bearing or immunized against aminoazo dye-induced rat hepatomas or 3-methylcholanthrene-induced rat sarcomas were pretreated with 3 M KCl extracts of these tumors, their cytotoxicity for cultured cells from the corresponding tumour was specificially inhibited. In cross-test combinations of target tumour and tumour-bearer effector-cell donor, tumour extracts only inhibited cytotoxic responses when they were derived from the tumour homologous to the target-cell and not when the extract was from the tumour borne by the effector-cell donor. One component of the tumour-bearer cytotoxic response was shown to be directed against tumour-associated embryonic antigens since soluble extracts of embryos or tumour extracts containing embryonic antigens inhibited tumour-bearer cell-mediated cytotoxicity in both specific and cross-test combinations of target tumour and effector cells. These findings are discussed in relation to tumour antigen expression and the immune responses that these tumour-associated antigens may evoke in tumour-bearing rats.", "contents": "Inhibition of cell-mediated cytotoxicity to chemically induced rat tumours by soluble tumour and embryo cell extracts. When lymph-node and spleen cells from rats bearing or immunized against aminoazo dye-induced rat hepatomas or 3-methylcholanthrene-induced rat sarcomas were pretreated with 3 M KCl extracts of these tumors, their cytotoxicity for cultured cells from the corresponding tumour was specificially inhibited. In cross-test combinations of target tumour and tumour-bearer effector-cell donor, tumour extracts only inhibited cytotoxic responses when they were derived from the tumour homologous to the target-cell and not when the extract was from the tumour borne by the effector-cell donor. One component of the tumour-bearer cytotoxic response was shown to be directed against tumour-associated embryonic antigens since soluble extracts of embryos or tumour extracts containing embryonic antigens inhibited tumour-bearer cell-mediated cytotoxicity in both specific and cross-test combinations of target tumour and effector cells. These findings are discussed in relation to tumour antigen expression and the immune responses that these tumour-associated antigens may evoke in tumour-bearing rats."} {"id": "PMID:175022", "title": "A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells.", "content": "The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency.", "contents": "A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency."} {"id": "PMID:175023", "title": "Comparative studies of Epstein-Barr virus strains from Ghana and the United States.", "content": "A high incidence of oropharyngeal excretion of Epstein-Barr virus (EBV) has been observed in African children with Burkitt's lymphoma (BL) (48%) and matched controls (45%). This compares with an incidence of 77% in American patients with infectious mononucleosis (IM) and 13% in age-matched controls. Cross-neutralization tests between EBV strains derived from BL and IM patients and their sera failed to detect differences in the major neutralizing antigenic components. Cord-blood lymphocytes transformed by American EBV expressed only early viral functions (EBV nuclear and soluble complement-fixing antigens) and produced no detectable transforming activity. By contrast, cord-blood lymphocytes transformed by African EBV strains contained 0.2-0.3% of cells with EBV capsid and early antigen and produced EBV with transforming activity. These cells contained twice as many copies of EBV homologous DNA as the cells transformed by American EBV strains.", "contents": "Comparative studies of Epstein-Barr virus strains from Ghana and the United States. A high incidence of oropharyngeal excretion of Epstein-Barr virus (EBV) has been observed in African children with Burkitt's lymphoma (BL) (48%) and matched controls (45%). This compares with an incidence of 77% in American patients with infectious mononucleosis (IM) and 13% in age-matched controls. Cross-neutralization tests between EBV strains derived from BL and IM patients and their sera failed to detect differences in the major neutralizing antigenic components. Cord-blood lymphocytes transformed by American EBV expressed only early viral functions (EBV nuclear and soluble complement-fixing antigens) and produced no detectable transforming activity. By contrast, cord-blood lymphocytes transformed by African EBV strains contained 0.2-0.3% of cells with EBV capsid and early antigen and produced EBV with transforming activity. These cells contained twice as many copies of EBV homologous DNA as the cells transformed by American EBV strains."} {"id": "PMID:175024", "title": "Humoral immune responses of cats to mammalian type-C virus p30s.", "content": "Natural and experimental cat sera were tested in radioimmune precipitation assays vs purified p30s from FeLV, RD114 and MuLV. Antibodies with specificity for FeLV p30 comparable to hyperimmune sera from heterologous species but of low titer were found in a high percentage of normal cats from households with a high incidence of FeLV and neoplasia. Sera from cats with neoplasms were generally negative. Cats immunized with FeLV gave low-level immune response, also of the same general specificity as heterologous hyperimmune sera. Cat sera do not normally show antibody to RD114 p30 although two immunized weanling cats produced low titered but highly specific p30 antibody. Thus, for both classes of feline type-C virus p30s, there is an evident capability of the cat to mount an immune response to natural or experimental exposure to the respective proteins. The magnitude of the response is between 100 and 1,000 fold below that seen in heterologous species. In contrast, cats immunized with MuLV p30 gave immune responses comparable to those seen in guinea-pigs, rabbits and goats. Several very old cats with carcinoma had antibody which preferentially precipitated MuVL p30. A competition assay using one such serum and labelled MuVL p30 was inhibited by FeVL, RD114, and MuLV p30s. This indicates that the assay is \"interspecies\" in nature. Among the possible explanations of this reaction category is that it represents antibody to the p30 of an as yet undefined class of feline type-C virus.", "contents": "Humoral immune responses of cats to mammalian type-C virus p30s. Natural and experimental cat sera were tested in radioimmune precipitation assays vs purified p30s from FeLV, RD114 and MuLV. Antibodies with specificity for FeLV p30 comparable to hyperimmune sera from heterologous species but of low titer were found in a high percentage of normal cats from households with a high incidence of FeLV and neoplasia. Sera from cats with neoplasms were generally negative. Cats immunized with FeLV gave low-level immune response, also of the same general specificity as heterologous hyperimmune sera. Cat sera do not normally show antibody to RD114 p30 although two immunized weanling cats produced low titered but highly specific p30 antibody. Thus, for both classes of feline type-C virus p30s, there is an evident capability of the cat to mount an immune response to natural or experimental exposure to the respective proteins. The magnitude of the response is between 100 and 1,000 fold below that seen in heterologous species. In contrast, cats immunized with MuLV p30 gave immune responses comparable to those seen in guinea-pigs, rabbits and goats. Several very old cats with carcinoma had antibody which preferentially precipitated MuVL p30. A competition assay using one such serum and labelled MuVL p30 was inhibited by FeVL, RD114, and MuLV p30s. This indicates that the assay is \"interspecies\" in nature. Among the possible explanations of this reaction category is that it represents antibody to the p30 of an as yet undefined class of feline type-C virus."} {"id": "PMID:175025", "title": "Immunity to antigens associated with a cell line derived from nasopharyngeal cancer (NPC) in non-Chinese NPC patients.", "content": "Delayed hypersensibility to antigens derived from four lymphoid cell lines was measured in 27 non-Chinese patients with nasopharyngeal cancer (NPC) and 63 non-NPC cancer patients. Of the NPC patients, 17/27 (63%) had a positive skin test response to antigens derived from HKLY-28, a lymphoid cell line which was developed from an NPC biopsy. Only 10/51 (20%) and 1/13 (8%) patients with solid tumors and hematopoietic malignancies, respectively, had positive skin test responses to HKLY-28. Positive skin tests were found less frequently when extracts from cell lines derived from normal individuals or lymphoma patients were utilized, although NPC patients were more reactive to two of the non-NPC derived cell lines than the controls. The NPC patients in this study also had significantly elevated antibody titers to the Epstein-Barr virus (EBV), capsid antigen (VCA) and early antigen (EA). Titers were highest in the patients with more anaplastic nasopharyngeal carcinomas. The skin test and serologic data are consistent with studies in Chinese patients, indicating that NPC in non-Chinese and Chinese patients is biologically similar.", "contents": "Immunity to antigens associated with a cell line derived from nasopharyngeal cancer (NPC) in non-Chinese NPC patients. Delayed hypersensibility to antigens derived from four lymphoid cell lines was measured in 27 non-Chinese patients with nasopharyngeal cancer (NPC) and 63 non-NPC cancer patients. Of the NPC patients, 17/27 (63%) had a positive skin test response to antigens derived from HKLY-28, a lymphoid cell line which was developed from an NPC biopsy. Only 10/51 (20%) and 1/13 (8%) patients with solid tumors and hematopoietic malignancies, respectively, had positive skin test responses to HKLY-28. Positive skin tests were found less frequently when extracts from cell lines derived from normal individuals or lymphoma patients were utilized, although NPC patients were more reactive to two of the non-NPC derived cell lines than the controls. The NPC patients in this study also had significantly elevated antibody titers to the Epstein-Barr virus (EBV), capsid antigen (VCA) and early antigen (EA). Titers were highest in the patients with more anaplastic nasopharyngeal carcinomas. The skin test and serologic data are consistent with studies in Chinese patients, indicating that NPC in non-Chinese and Chinese patients is biologically similar."} {"id": "PMID:175026", "title": "Establishment of EBNA-expressing cell lines by infection of Epstein-Barr virus (EBV)-genome-negative human lymphoma cells with different EBV strains.", "content": "Cells of two EBNA (Epstein-Barr virus nuclear antigen)-negative human lymphoma cell lines, BJAB and RAMOS, were infected with two strains of Epstein-Barr virus (EBV). In two different experiments, B95-8 virus-infected BJAB cells revealed a gradually increasing number of EBNA-positive cells. Twenty weeks after infection almost 100% of the cell population expressed this antigen. In contrast, it has not so far been possible to convert RAMOS cells into an EBNA-positive cell line. The initial proportion of 35% EBNA-positive cells declined to about 10% 20 weeks after infection. The development of EBNA-positive multinuclear giant cells was a characteristic feature of infection with B95-8 virus. EA (early antigen) and VCA (virus capsid antigen) appeared in less than 0.1% of the cell population after induction with IUdR only. Infection of BJAB and RAMOS cells with P3HR-1 virus finally resulted in both cases in EBNA-positive lines. In contrast to B95-8 virus, the number of EBNA-positive lines. In contrast to B95-8 virus, the number of EBNA-positive cells remained below 1% during the first 6 to 8 weeks. A sudden increase occurred thereafter, bringing the number of EBNA-expressing cells to almost 100% within the following 4 weeks. During this period, BJAB but not RAMOS cells revealed a small number of EA- as well as VCA-positive cells (less than 0.1%). Thus, reinfection by spontaneously released virus may explain the sudden increase in EBNA-positive BJAB cells. Two distinct patterns of EBNA staining in P3HR-1 virus-infected cells were observed. They may suggest a genetic heterogeneity of this virus preparation.", "contents": "Establishment of EBNA-expressing cell lines by infection of Epstein-Barr virus (EBV)-genome-negative human lymphoma cells with different EBV strains. Cells of two EBNA (Epstein-Barr virus nuclear antigen)-negative human lymphoma cell lines, BJAB and RAMOS, were infected with two strains of Epstein-Barr virus (EBV). In two different experiments, B95-8 virus-infected BJAB cells revealed a gradually increasing number of EBNA-positive cells. Twenty weeks after infection almost 100% of the cell population expressed this antigen. In contrast, it has not so far been possible to convert RAMOS cells into an EBNA-positive cell line. The initial proportion of 35% EBNA-positive cells declined to about 10% 20 weeks after infection. The development of EBNA-positive multinuclear giant cells was a characteristic feature of infection with B95-8 virus. EA (early antigen) and VCA (virus capsid antigen) appeared in less than 0.1% of the cell population after induction with IUdR only. Infection of BJAB and RAMOS cells with P3HR-1 virus finally resulted in both cases in EBNA-positive lines. In contrast to B95-8 virus, the number of EBNA-positive lines. In contrast to B95-8 virus, the number of EBNA-positive cells remained below 1% during the first 6 to 8 weeks. A sudden increase occurred thereafter, bringing the number of EBNA-expressing cells to almost 100% within the following 4 weeks. During this period, BJAB but not RAMOS cells revealed a small number of EA- as well as VCA-positive cells (less than 0.1%). Thus, reinfection by spontaneously released virus may explain the sudden increase in EBNA-positive BJAB cells. Two distinct patterns of EBNA staining in P3HR-1 virus-infected cells were observed. They may suggest a genetic heterogeneity of this virus preparation."} {"id": "PMID:175027", "title": "Attempts to demonstrate virus-specific sequences in human tumors. IV. EB viral DNA in European Burkitt lymphoma and immunoblastic lymphadenopathy with excessive plasmacytosis.", "content": "Various biopsies from different European malignant lymphomas, two biopsies from nasopharyngeal carcinomas, and material from non-neoplastic lymph nodes were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization. Reassociation kinetics of in vitro-labelled EBV DNA were studied in the presence of tumor DNA. The lymphomas tested included among others follicular lymphomas, germinocytomas, immunoblastic lymphomas and lymphoplasmacytoid immunocytomas. Epstein-Barr viral DNA was demonstrated within the two nasopharyngeal carcinoma biopsies as expected. A histologically typical Burkitt lymphoma as well as an immunoblastic lymphadenopathy with excessive plasmacytosis also contained EBV-DNA. The Burkitt biopsy revealed about 15 EBV genome equivalents per cell. Antibodies against EBV-specific antigens were highly elevated in the serum of this patient. The material of the patient with immunoblastic lymphadenopathy contained 2-3 EBV genome equivalents per cell.", "contents": "Attempts to demonstrate virus-specific sequences in human tumors. IV. EB viral DNA in European Burkitt lymphoma and immunoblastic lymphadenopathy with excessive plasmacytosis. Various biopsies from different European malignant lymphomas, two biopsies from nasopharyngeal carcinomas, and material from non-neoplastic lymph nodes were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization. Reassociation kinetics of in vitro-labelled EBV DNA were studied in the presence of tumor DNA. The lymphomas tested included among others follicular lymphomas, germinocytomas, immunoblastic lymphomas and lymphoplasmacytoid immunocytomas. Epstein-Barr viral DNA was demonstrated within the two nasopharyngeal carcinoma biopsies as expected. A histologically typical Burkitt lymphoma as well as an immunoblastic lymphadenopathy with excessive plasmacytosis also contained EBV-DNA. The Burkitt biopsy revealed about 15 EBV genome equivalents per cell. Antibodies against EBV-specific antigens were highly elevated in the serum of this patient. The material of the patient with immunoblastic lymphadenopathy contained 2-3 EBV genome equivalents per cell."} {"id": "PMID:175028", "title": "Clonal transformation of human leukocytes by Epstein-Barr virus in soft agar.", "content": "The B95-8 strain of Epstein-Barr virus (EBV) induced colony formation of human umbilical cord-blood leukocytes in soft agar medium. One-hit response relationship between the number of colonies and the virus dose was observed with high dilutions of the virus preparation. However, there was a presumed cell-killing effect with low dilutions of virus. The colonies were similarly induced, but with a lower efficiency, in adult peripheral blood leukocyte cultures infected with the virus. The colony-forming activity of EBV was neutralized by anti-EBV-positive but not by negative human sera. The cells in colonies were capable of growing continuously and carried EBV-associated nuclear antigen. Thus, it was evident that the colony formation was caused by clonal transformation by EBV.", "contents": "Clonal transformation of human leukocytes by Epstein-Barr virus in soft agar. The B95-8 strain of Epstein-Barr virus (EBV) induced colony formation of human umbilical cord-blood leukocytes in soft agar medium. One-hit response relationship between the number of colonies and the virus dose was observed with high dilutions of the virus preparation. However, there was a presumed cell-killing effect with low dilutions of virus. The colonies were similarly induced, but with a lower efficiency, in adult peripheral blood leukocyte cultures infected with the virus. The colony-forming activity of EBV was neutralized by anti-EBV-positive but not by negative human sera. The cells in colonies were capable of growing continuously and carried EBV-associated nuclear antigen. Thus, it was evident that the colony formation was caused by clonal transformation by EBV."} {"id": "PMID:175029", "title": "Lack of correlation between Marena tumor induction and expression of endogenous avian RNA tumor virus genome.", "content": "Infection with Marek's disease virus (MDV) and subsequent tumor development failed to induce the expression of endogenous avian RNA tumor virus genome in Line-15I and Line-7 chickens which lacked such expression at 1 day of age. Titers of avian leukosis virus (ALV) group-specific (gs) antigen detected by the COFAL test and expression of chick helper factor (chf) activity remained relatively constant in birds which expressed these genome functions at hatching time. Endogenous ALV belonging to the E-subgroup was isolated from two of 50 birds; both were controls not exposed to MDV. There was no correlation between expression of ALV genome (gs or chf) at 1 day of age and the rate of tumor development subsequent ot MDV infection. It was concluded that MDV infection can induce tumors without the participation of endogenous ALV genome.", "contents": "Lack of correlation between Marena tumor induction and expression of endogenous avian RNA tumor virus genome. Infection with Marek's disease virus (MDV) and subsequent tumor development failed to induce the expression of endogenous avian RNA tumor virus genome in Line-15I and Line-7 chickens which lacked such expression at 1 day of age. Titers of avian leukosis virus (ALV) group-specific (gs) antigen detected by the COFAL test and expression of chick helper factor (chf) activity remained relatively constant in birds which expressed these genome functions at hatching time. Endogenous ALV belonging to the E-subgroup was isolated from two of 50 birds; both were controls not exposed to MDV. There was no correlation between expression of ALV genome (gs or chf) at 1 day of age and the rate of tumor development subsequent ot MDV infection. It was concluded that MDV infection can induce tumors without the participation of endogenous ALV genome."} {"id": "PMID:175030", "title": "Serum factor levels during the growth of rat hepatoma nodules in the lungs.", "content": "The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour-specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour-specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour-specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed.", "contents": "Serum factor levels during the growth of rat hepatoma nodules in the lungs. The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour-specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour-specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour-specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed."} {"id": "PMID:175031", "title": "Fibroblast surface antigen (SF): the external glycoprotein lost in proteolytic stimulation and maligant transfromation.", "content": "It was previously shown that the fibroblast surface antigen (SF antigen, SFA) is composed of polypeptides of high molecular weight 210,000 (SF210) and 145,000 (SF145) and that both of these decrease in quantity after transformation of the fibroblasts by Rous sarcoma virus (RSV). The present experiments show that SF210 is a glycoprotein. It is accessible to surface labelling by lactoperoxidase catalyzed iodination. The SF210 molecule is highly susceptible to trypsin on cell surface. Anti-SFA antibodies specifically precipitated the surface labelled polypeptide. The lactoperoxidase iodinated SF210 polypeptide was greatly reduced in cells transformed by RSV. It is concluded from these studies that the large external transformation sensitive (LETS) protein detected by other workers is the same molecule as SF210. Part of the label of surface iodinated fibroblasts did not enter the polyacrylamide gels. This high molecular weight material is also susceptible to trypsin treatment and decreases in quantity after transformation by RSV. The data suggest that it may be antigenically related to SF protein. Treatment of surface of 35S-methionine-labelled cultures with trypsin in concentrations able to initiate proliferation of density-inhibited cells rapidly released SF210 from fibroblast surface. A single high molecular weight polypeptide (mol. wt about 200,000, SF200) was detected in the culture medium. SF210 may thus be a major target molecule of trypsin action. Treatment of cultures with insulin that also stimulated the fibroblasts to initiate proliferation did not result in any detectable alteration in the external glycoprotein SF210. It is concluded that although release of SF210 may be a sufficient trigger to stimulate proliferation in stationary cells, this molecule appears not to be directly involved in initiation of fibroblast proliferation from the G1 (or G0) phase of the cell cycle.", "contents": "Fibroblast surface antigen (SF): the external glycoprotein lost in proteolytic stimulation and maligant transfromation. It was previously shown that the fibroblast surface antigen (SF antigen, SFA) is composed of polypeptides of high molecular weight 210,000 (SF210) and 145,000 (SF145) and that both of these decrease in quantity after transformation of the fibroblasts by Rous sarcoma virus (RSV). The present experiments show that SF210 is a glycoprotein. It is accessible to surface labelling by lactoperoxidase catalyzed iodination. The SF210 molecule is highly susceptible to trypsin on cell surface. Anti-SFA antibodies specifically precipitated the surface labelled polypeptide. The lactoperoxidase iodinated SF210 polypeptide was greatly reduced in cells transformed by RSV. It is concluded from these studies that the large external transformation sensitive (LETS) protein detected by other workers is the same molecule as SF210. Part of the label of surface iodinated fibroblasts did not enter the polyacrylamide gels. This high molecular weight material is also susceptible to trypsin treatment and decreases in quantity after transformation by RSV. The data suggest that it may be antigenically related to SF protein. Treatment of surface of 35S-methionine-labelled cultures with trypsin in concentrations able to initiate proliferation of density-inhibited cells rapidly released SF210 from fibroblast surface. A single high molecular weight polypeptide (mol. wt about 200,000, SF200) was detected in the culture medium. SF210 may thus be a major target molecule of trypsin action. Treatment of cultures with insulin that also stimulated the fibroblasts to initiate proliferation did not result in any detectable alteration in the external glycoprotein SF210. It is concluded that although release of SF210 may be a sufficient trigger to stimulate proliferation in stationary cells, this molecule appears not to be directly involved in initiation of fibroblast proliferation from the G1 (or G0) phase of the cell cycle."} {"id": "PMID:175033", "title": "Effect of age on activities of urea cycle enzymes in the bovine.", "content": "Eighteen Hereford cows averaging 429.6 +/- 14.5 kg in weight, ranging from 3.33 to 12.12 years of age and consuming 18.2 kg corn silage/animal/day were used to observe the effect of age on activities of the liver enzymes of urea synthesis. Liver samples were taken by aspiration biopsy and homogenized in water for enzyme assay. Plasma urea-nitrogen of all cows averaged 4.20 mg per 100 ml. The enzymes measured were: carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (AS), argininosuccinase (AL) and arginase (A). Mean enzyme activities of the cows were: CPS 1.57, OTC 44.4, AS 0.61, AL 1.05 and A 203.9 mum product/mg protein/hr. Regression coefficients (b) of enzyme activity (units) on age (years) were 0.021 +/- .018, 0.713 +/- .379, 0.016 +/- .016, 0.032 +/- .014 and 6.73 +/- 5.09 units for the five enzymes, respectively. Age (3.3 to 12.1 years) did not significantly (P less than .05) affect activities of the urea cycle enzymes (per mg protein, per g liver or per W-75 kg/hr) or plasma urea-nitrogen levels in the adult Hereford female at the level of dietary protein fed in this study.", "contents": "Effect of age on activities of urea cycle enzymes in the bovine. Eighteen Hereford cows averaging 429.6 +/- 14.5 kg in weight, ranging from 3.33 to 12.12 years of age and consuming 18.2 kg corn silage/animal/day were used to observe the effect of age on activities of the liver enzymes of urea synthesis. Liver samples were taken by aspiration biopsy and homogenized in water for enzyme assay. Plasma urea-nitrogen of all cows averaged 4.20 mg per 100 ml. The enzymes measured were: carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (AS), argininosuccinase (AL) and arginase (A). Mean enzyme activities of the cows were: CPS 1.57, OTC 44.4, AS 0.61, AL 1.05 and A 203.9 mum product/mg protein/hr. Regression coefficients (b) of enzyme activity (units) on age (years) were 0.021 +/- .018, 0.713 +/- .379, 0.016 +/- .016, 0.032 +/- .014 and 6.73 +/- 5.09 units for the five enzymes, respectively. Age (3.3 to 12.1 years) did not significantly (P less than .05) affect activities of the urea cycle enzymes (per mg protein, per g liver or per W-75 kg/hr) or plasma urea-nitrogen levels in the adult Hereford female at the level of dietary protein fed in this study."} {"id": "PMID:175034", "title": "[The angioleiomyoma of the skin].", "content": "Twelve cases of angioleiomyoma are reported. These are benign, often painful tumors occurring chiefly on the lower extremities of middle-aged women. Clinical diagnosis is usually possible, and any remaining doubt can easily be resolved by histological examinations.", "contents": "[The angioleiomyoma of the skin]. Twelve cases of angioleiomyoma are reported. These are benign, often painful tumors occurring chiefly on the lower extremities of middle-aged women. Clinical diagnosis is usually possible, and any remaining doubt can easily be resolved by histological examinations."} {"id": "PMID:175035", "title": "[The photodynamic effect in Herpes simplex: a review].", "content": "Photodynamic action is an extraordinarily potent physicochemical process which is dramatically lethal for herpesvirus and other organisms in vitro. Recent studies in animal models and man indicate that the process is effective against in vivo skin infections as well. Although a great deal is yet to be learned about the application of photodynamic action to clinical disease, current experience indicates that photodynamic action will find a permanent place in the physician's therapeutic armamentarium.", "contents": "[The photodynamic effect in Herpes simplex: a review]. Photodynamic action is an extraordinarily potent physicochemical process which is dramatically lethal for herpesvirus and other organisms in vitro. Recent studies in animal models and man indicate that the process is effective against in vivo skin infections as well. Although a great deal is yet to be learned about the application of photodynamic action to clinical disease, current experience indicates that photodynamic action will find a permanent place in the physician's therapeutic armamentarium."} {"id": "PMID:175036", "title": "[Diagnostic errors and their reasons in tumors and preblastomatoses of the skin. Results of a statistical evaluation].", "content": "Clinical and histological findings and other available data of 6 521 skin excisates were compared with regard to differential diagnosis. It appears from our findings, that \"naive\" experience must be replaced by secured knowledge concerning frequencies of wrong diagnoses in definite situations, possible causes of errors, age-, sex-, and local distribution of different skin tumours. This knowledge may be a contribution to the improvement of clinical diagnoses.", "contents": "[Diagnostic errors and their reasons in tumors and preblastomatoses of the skin. Results of a statistical evaluation]. Clinical and histological findings and other available data of 6 521 skin excisates were compared with regard to differential diagnosis. It appears from our findings, that \"naive\" experience must be replaced by secured knowledge concerning frequencies of wrong diagnoses in definite situations, possible causes of errors, age-, sex-, and local distribution of different skin tumours. This knowledge may be a contribution to the improvement of clinical diagnoses."} {"id": "PMID:175038", "title": "Morphometric and enzyme histochemical behaviour of the kidney of young rats before and after unilateral nephrectomy.", "content": "Four week old male Wistar rats were unilaterally nephrectomized, and one, two, four, fourteen, and twenty-eight days after the operation the remaining kidneys were removed for morphological examination--including measurement of diameters of the tubules--and for histochemical investigation of enzymatic activities in the nephrons. The following enzymes were examined: succinate DH, lactate DH, alpha-glycerophosphate DH, isocitrate DH, glucose-6-phosphate DH, cytochrome oxidase, adenosine triphosphatase, alkaline and acid phosphatases. In comparison with kidneys of control animals of the same age and sex, the hypertrophy of the remaining kidney was found to be, even in these young rats, entirely due to enlargement of preexisting nephrons. The measurements have indicated that the hypertrophy was most distinct between the second and fourth day after uninephrectomy. Four weeks after the operation the diameters of proximal and distal tubules were about 21% and 18% respectively bigger in the uninephrectomized animals than in the corresponding controls. This increase in size was accompanied by some changes in intensity of enzymatic staining reactions; after an initial diminishment, a graduate increase in activity of almost all the observed tubular enzymes was found; this seems to be the expression of the functional compensation by the remaining kidney.", "contents": "Morphometric and enzyme histochemical behaviour of the kidney of young rats before and after unilateral nephrectomy. Four week old male Wistar rats were unilaterally nephrectomized, and one, two, four, fourteen, and twenty-eight days after the operation the remaining kidneys were removed for morphological examination--including measurement of diameters of the tubules--and for histochemical investigation of enzymatic activities in the nephrons. The following enzymes were examined: succinate DH, lactate DH, alpha-glycerophosphate DH, isocitrate DH, glucose-6-phosphate DH, cytochrome oxidase, adenosine triphosphatase, alkaline and acid phosphatases. In comparison with kidneys of control animals of the same age and sex, the hypertrophy of the remaining kidney was found to be, even in these young rats, entirely due to enlargement of preexisting nephrons. The measurements have indicated that the hypertrophy was most distinct between the second and fourth day after uninephrectomy. Four weeks after the operation the diameters of proximal and distal tubules were about 21% and 18% respectively bigger in the uninephrectomized animals than in the corresponding controls. This increase in size was accompanied by some changes in intensity of enzymatic staining reactions; after an initial diminishment, a graduate increase in activity of almost all the observed tubular enzymes was found; this seems to be the expression of the functional compensation by the remaining kidney."} {"id": "PMID:175039", "title": "In vitro induction of tyrosinase activity in goldfish (Carassius auratus L.) integument by ACTH and dibutyryl-cAMP.", "content": "Tyrosinase was first detected in melanoblasts by the DOPA-oxidase reaction in the presence of catalase in explants of goldfish integument after 12 hr culture with either ACTH (1IU/ml) or DB-cAMP (0.1mM). Melanin did not appear in the new melanocytes until 24 hr. The data indicate that the release of cAMP within the melanoblast in response to ACTH treatment is rapid and the tyrosinase in the melanoblast is released from inhibition and/or activated at least 12 hr prior to melanization of premelanosomes.", "contents": "In vitro induction of tyrosinase activity in goldfish (Carassius auratus L.) integument by ACTH and dibutyryl-cAMP. Tyrosinase was first detected in melanoblasts by the DOPA-oxidase reaction in the presence of catalase in explants of goldfish integument after 12 hr culture with either ACTH (1IU/ml) or DB-cAMP (0.1mM). Melanin did not appear in the new melanocytes until 24 hr. The data indicate that the release of cAMP within the melanoblast in response to ACTH treatment is rapid and the tyrosinase in the melanoblast is released from inhibition and/or activated at least 12 hr prior to melanization of premelanosomes."} {"id": "PMID:175040", "title": "The ultrastructural localisation of cadmium.", "content": "A modified technique for the ultrastructural localisation of heavy metals is described in this paper. The method involves precipitation of heavy metals as sulphides in the tissue by using (NH4)2 S after brief fixation in glutaraldehyde. The sulphides are, in the presence of a physical developer, then used to catalyse the reduction of silver ions into visible molecular silver. This latter step of physical development has been normally carried out after embedding and sectioning. However, when we followed this method we found that the dark metal sulphide was lost from the tissue during the embedding in epoxy resin. Hence the method was unsuitable for our proposed experiment on the ultrastructural localisation of cadmium. We subsequently modified the technique primarily by treating very thin tissue slices with the developer before dehydration and embedding, thus eliminating any problem from sulphide loss. This modified technique was used to investigate the ultrastructural localisation of cadmium in the kidneys of mice which had been exposed to 50 ppm cadmium in their drinking water for up to eight months. The molecular silver was found to be located mainly in the proximal tubule cells, either as dense clumps in apical vesicles and lysosomes or diffuse grains throughout the cytoplasm of the cells particularly in the basal region. We interpret these results as indicating that cadmium is found in the apical vesicles, lysosomes and cytoplasm of proximal tubule cells.", "contents": "The ultrastructural localisation of cadmium. A modified technique for the ultrastructural localisation of heavy metals is described in this paper. The method involves precipitation of heavy metals as sulphides in the tissue by using (NH4)2 S after brief fixation in glutaraldehyde. The sulphides are, in the presence of a physical developer, then used to catalyse the reduction of silver ions into visible molecular silver. This latter step of physical development has been normally carried out after embedding and sectioning. However, when we followed this method we found that the dark metal sulphide was lost from the tissue during the embedding in epoxy resin. Hence the method was unsuitable for our proposed experiment on the ultrastructural localisation of cadmium. We subsequently modified the technique primarily by treating very thin tissue slices with the developer before dehydration and embedding, thus eliminating any problem from sulphide loss. This modified technique was used to investigate the ultrastructural localisation of cadmium in the kidneys of mice which had been exposed to 50 ppm cadmium in their drinking water for up to eight months. The molecular silver was found to be located mainly in the proximal tubule cells, either as dense clumps in apical vesicles and lysosomes or diffuse grains throughout the cytoplasm of the cells particularly in the basal region. We interpret these results as indicating that cadmium is found in the apical vesicles, lysosomes and cytoplasm of proximal tubule cells."} {"id": "PMID:175043", "title": "Pulmonary shunt: a comparison between oxygen and inert gas infusion methods.", "content": "Pulmonary shunt measurement was compared using the standard oxygen (Berggren) technique and a new multiple inert gas infusion (Wagner et al.) technique in 11 mongrel dogs with either regional atelectasis or diffuse pulmonary edema. Relative retentions of sulfur hexafluoride, ethane, cyclopropane, halothane, diethyl ether, and acetone were used to calculate intrapulmonary shunt. Relative dilution of oxygen (Berggren method) was used to calculate total right to left shunt. The two methods gave similar results in the range of 20-80%. At low shunts the oxygen method measured higher values. This is because of the greater relative importance of fixed extrapulmonary shunts at this level and, as well, error in the measurement of PO2. Both techniques are suitable for normal clinical use.", "contents": "Pulmonary shunt: a comparison between oxygen and inert gas infusion methods. Pulmonary shunt measurement was compared using the standard oxygen (Berggren) technique and a new multiple inert gas infusion (Wagner et al.) technique in 11 mongrel dogs with either regional atelectasis or diffuse pulmonary edema. Relative retentions of sulfur hexafluoride, ethane, cyclopropane, halothane, diethyl ether, and acetone were used to calculate intrapulmonary shunt. Relative dilution of oxygen (Berggren method) was used to calculate total right to left shunt. The two methods gave similar results in the range of 20-80%. At low shunts the oxygen method measured higher values. This is because of the greater relative importance of fixed extrapulmonary shunts at this level and, as well, error in the measurement of PO2. Both techniques are suitable for normal clinical use."} {"id": "PMID:175044", "title": "Resolution of aflatoxins B1, B2, G1, and G2 by high-pressure liquid chromatography.", "content": "Aflatoxins were completely resolved as sharp peaks in the order BU-B2-G1-G2 by high-pressure liquid chromatography on a small particle (10 mum) porous silica gel column in 7-13 min (B1 through G2) by a water-saturated chloroform-cyclohexane-acetonitrile elution solvent (25+7.5+1.0), with detection by ultraviolet absorbance at 360 nm. The relationship between peak height and amount injected was linear over a 5-400 ng range for each aflatoxin. Both retention times and peak heights were highly reproducible, multiple injections of mixed standards giving coefficients of variation of 1.0-1.4% (retention time) and 1.6-2.8% (peak height) for the 4 aflatoxins. Detection was highly sensitive, with mean peak height, mm/ng, of 7.1 (B1), 6.4 (B2), 4.5 (G1), and 4.1(G2), allowing detection of 1-2 ng of each aflatoxin.", "contents": "Resolution of aflatoxins B1, B2, G1, and G2 by high-pressure liquid chromatography. Aflatoxins were completely resolved as sharp peaks in the order BU-B2-G1-G2 by high-pressure liquid chromatography on a small particle (10 mum) porous silica gel column in 7-13 min (B1 through G2) by a water-saturated chloroform-cyclohexane-acetonitrile elution solvent (25+7.5+1.0), with detection by ultraviolet absorbance at 360 nm. The relationship between peak height and amount injected was linear over a 5-400 ng range for each aflatoxin. Both retention times and peak heights were highly reproducible, multiple injections of mixed standards giving coefficients of variation of 1.0-1.4% (retention time) and 1.6-2.8% (peak height) for the 4 aflatoxins. Detection was highly sensitive, with mean peak height, mm/ng, of 7.1 (B1), 6.4 (B2), 4.5 (G1), and 4.1(G2), allowing detection of 1-2 ng of each aflatoxin."} {"id": "PMID:175045", "title": "Alpha reduced nicotinamide adenine dinucleotide-dependent reductase reactions of rat liver microsomes.", "content": "The kinetics of alpha-NADH-dichlorophenolindophenol (DCPIP) and alpha-NADH-cytochrome c reductase reactions of rat liver microsomes showed that the reactio ns proceeded by a ping-pong mechanism, and that the oxidation of alpha-NADH was the rate-determining reaction. The DCPIP-reducing activity with alpha-NADH in the presence of ADP was about 1% of that with beta-NADH. ADP inhibited the alpha-NADH-DCPIP reductase reaction in a competitive manner with respect to alpha-NADH and a value of 1.2 mM for the inhibition constant was obtained. ADP also inhibited cytochrome b5 reduction with alpha-NADH. More than 90% of cytochrome b5 was reduced under conditions where 90% of the alpha-NADH-DCPIP reductase activity was suppressed with ADP. The reduction of DCPIP with alpha-NADH preceded that of cytochrome b5, but the reductions partly overlapped. From these results, a diversed electron flow from alpha-NADH to cytochrome b5 and electron sharing between cytochrome b5 and DCPIP were indicated. alpha-NAD+ also inhibited the alpha-NADH-DCPIP reductase reaction. Analyses of the inhibition indicated that two types of alpha-NADH-DCPIP reductase reaction existed, one of which was resistant to alpha-NAD+ inhibition. In contrast to the reoxidation of beta-NADH-reduced cytochrome b5, the process was largely monophasic when cytochrome b5 was reduced with alpha-NADH.", "contents": "Alpha reduced nicotinamide adenine dinucleotide-dependent reductase reactions of rat liver microsomes. The kinetics of alpha-NADH-dichlorophenolindophenol (DCPIP) and alpha-NADH-cytochrome c reductase reactions of rat liver microsomes showed that the reactio ns proceeded by a ping-pong mechanism, and that the oxidation of alpha-NADH was the rate-determining reaction. The DCPIP-reducing activity with alpha-NADH in the presence of ADP was about 1% of that with beta-NADH. ADP inhibited the alpha-NADH-DCPIP reductase reaction in a competitive manner with respect to alpha-NADH and a value of 1.2 mM for the inhibition constant was obtained. ADP also inhibited cytochrome b5 reduction with alpha-NADH. More than 90% of cytochrome b5 was reduced under conditions where 90% of the alpha-NADH-DCPIP reductase activity was suppressed with ADP. The reduction of DCPIP with alpha-NADH preceded that of cytochrome b5, but the reductions partly overlapped. From these results, a diversed electron flow from alpha-NADH to cytochrome b5 and electron sharing between cytochrome b5 and DCPIP were indicated. alpha-NAD+ also inhibited the alpha-NADH-DCPIP reductase reaction. Analyses of the inhibition indicated that two types of alpha-NADH-DCPIP reductase reaction existed, one of which was resistant to alpha-NAD+ inhibition. In contrast to the reoxidation of beta-NADH-reduced cytochrome b5, the process was largely monophasic when cytochrome b5 was reduced with alpha-NADH."} {"id": "PMID:175046", "title": "Correlation between adenosine 3',5'-cyclic monosphosphate levels, adenylate cyclase activity, and adenosine 3',5'-cyclic monophosphate phosphodiesterase activity in tissue culture cells stimulated by serum.", "content": "Changes in the activity of adenylate cyclase [EC 4.6.1.1] of serum-stimulated hamster BHK cells in culture were investigated in relation to changes in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP). Addition of calf serum to quiescent cultures decreases the activity of adenylate cyclase, followed by cellular DNA synthesis. Cyclic AMP levels drop in parallel with the decrease in adenylate cyclase activity. Kinetic analysis of cyclic AMP phosphodiesterase [EC 3.1.4.17] revealed that BHK cells contain two forms of the enzyme, one with a Km of 0.77 muM and the other with Km of 17.0 muM. The activity of these enzymes is not affected by the addition of serum to tissue culture cells. The findings indicate that the decrease in adenylate cyclase activity is directly responsible for the decrease in cyclic AMP levels that is observed immediately after serum addition. Low levels of cyclic AMP continue for several hours during serum treatment, followed by a transient increase in cyclic AMP in the early stages of cellular DNA synthesis, at which time the activity of cyclic AMP phosphodiesterase with a low Km shows a slight decrease.", "contents": "Correlation between adenosine 3',5'-cyclic monosphosphate levels, adenylate cyclase activity, and adenosine 3',5'-cyclic monophosphate phosphodiesterase activity in tissue culture cells stimulated by serum. Changes in the activity of adenylate cyclase [EC 4.6.1.1] of serum-stimulated hamster BHK cells in culture were investigated in relation to changes in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP). Addition of calf serum to quiescent cultures decreases the activity of adenylate cyclase, followed by cellular DNA synthesis. Cyclic AMP levels drop in parallel with the decrease in adenylate cyclase activity. Kinetic analysis of cyclic AMP phosphodiesterase [EC 3.1.4.17] revealed that BHK cells contain two forms of the enzyme, one with a Km of 0.77 muM and the other with Km of 17.0 muM. The activity of these enzymes is not affected by the addition of serum to tissue culture cells. The findings indicate that the decrease in adenylate cyclase activity is directly responsible for the decrease in cyclic AMP levels that is observed immediately after serum addition. Low levels of cyclic AMP continue for several hours during serum treatment, followed by a transient increase in cyclic AMP in the early stages of cellular DNA synthesis, at which time the activity of cyclic AMP phosphodiesterase with a low Km shows a slight decrease."} {"id": "PMID:175047", "title": "The distribution of pyrophosphatidic acid in nature.", "content": "The occurrence of a novel phospholipid, pyrophosphatidic acid, in the lipid extracts of yeasts (23 species), bacteria (E. coli), algae (chlorella), mammalia (human, rabbit, guinea pig, and mouse), insect (cockroach), fish (carp), mollusc (clam), and spermatophyta (spinach) was investigated. Pyrophosphatidic acid was found exclusively in the lipid extracts of several kinds of yeast species, but not in other normal living species (animals, plants, and microorganisms) so far investigated. All of the yeast species containing this lipid belong to the asporogenous yeasts (Cryptococcus neoformans CBS-132, Cryptococcus laurentii Z 6-5, Rhodotorula glutinis H 3-9-1, Rhodotorula rubra AY-2, Kloeckera apiculata KK-3, and Trichosporon cutaneum KC 4-3), and ballistosporogenous yeast (Sporobolomyces salmonicolor WF 174). In contrast, no detectable amount of pyrophosphatidic acid was found in the cellular lipids of ascosporogenous yeasts.", "contents": "The distribution of pyrophosphatidic acid in nature. The occurrence of a novel phospholipid, pyrophosphatidic acid, in the lipid extracts of yeasts (23 species), bacteria (E. coli), algae (chlorella), mammalia (human, rabbit, guinea pig, and mouse), insect (cockroach), fish (carp), mollusc (clam), and spermatophyta (spinach) was investigated. Pyrophosphatidic acid was found exclusively in the lipid extracts of several kinds of yeast species, but not in other normal living species (animals, plants, and microorganisms) so far investigated. All of the yeast species containing this lipid belong to the asporogenous yeasts (Cryptococcus neoformans CBS-132, Cryptococcus laurentii Z 6-5, Rhodotorula glutinis H 3-9-1, Rhodotorula rubra AY-2, Kloeckera apiculata KK-3, and Trichosporon cutaneum KC 4-3), and ballistosporogenous yeast (Sporobolomyces salmonicolor WF 174). In contrast, no detectable amount of pyrophosphatidic acid was found in the cellular lipids of ascosporogenous yeasts."} {"id": "PMID:175048", "title": "Organization of lipids in sarcoplasmic reticulum membrane and Ca2+-dependent ATPase activity.", "content": "The organization of lipids in sarcoplasmic reticulum membrane was studied with a variety of stearic spin labels and a phosphatidylcholine spin label. The ESR spectra of the spin-labeled membranes consisted of two components, one due to labels in lipid bilayer structure and the other due to more immobilized labels. The relative intensity of the immobilized component increased when the lipid content of the membrane was decreased by treatment with phospholipase A [EC 3.1.1.4] and subsequent washing with bovine serum albumin. Membrane containing 30% of the intact phospholipid, i.e.0.15 mg of phospholipid per mg of protein, showed a spectrum consisting only of the immobilized component (the overall splitting ranged from 58.5 G to 60.5 G). The immobilized component was ascribed to lipids complexed with protein. The fraction of lipids in the two different organizations was determined from the ESR spectrum. The activity of the Ca2+-Mg2+ dependent ATPase [ATP phosphohydrolase, EC 3.6.1.3] was found to increase almost linearly with the lipid bilayer content in the membrane, whereas phosphoenzyme formation was almost independent of the bilayer content. This indicated that the bilayer structure is necessary for the ATPase to attain its full transport activity.", "contents": "Organization of lipids in sarcoplasmic reticulum membrane and Ca2+-dependent ATPase activity. The organization of lipids in sarcoplasmic reticulum membrane was studied with a variety of stearic spin labels and a phosphatidylcholine spin label. The ESR spectra of the spin-labeled membranes consisted of two components, one due to labels in lipid bilayer structure and the other due to more immobilized labels. The relative intensity of the immobilized component increased when the lipid content of the membrane was decreased by treatment with phospholipase A [EC 3.1.1.4] and subsequent washing with bovine serum albumin. Membrane containing 30% of the intact phospholipid, i.e.0.15 mg of phospholipid per mg of protein, showed a spectrum consisting only of the immobilized component (the overall splitting ranged from 58.5 G to 60.5 G). The immobilized component was ascribed to lipids complexed with protein. The fraction of lipids in the two different organizations was determined from the ESR spectrum. The activity of the Ca2+-Mg2+ dependent ATPase [ATP phosphohydrolase, EC 3.6.1.3] was found to increase almost linearly with the lipid bilayer content in the membrane, whereas phosphoenzyme formation was almost independent of the bilayer content. This indicated that the bilayer structure is necessary for the ATPase to attain its full transport activity."} {"id": "PMID:175049", "title": "Purification and properties of the intact form of NADH-cytochrome b5 reductase from rabbit liver microsomes.", "content": "NADH-cytochrome b5 reductase [EC 1.6.2.2] has been solubilized with Triton X-100 and purified to homogeneity from rabbit liver microsomes. The purified enzyme is essentially free of the detergent and phospholipids and exists in aqueous media as an oligomeric aggregate of about 13 S. Its monomeric molecular weight is about 33,000 and 1 mole of FAD is associated with 1 mole of the monomeric unit. The enzyme catalyzes the reductions by NADH of ferricyanide and 2,6-dichlorophenol indophenol at an activity ratio of 1 : 0.09. Although the intact form of cytochrome b5 is a poorer electron acceptor than its hydrophilic fragment for the purified flavoprotein, electron transfer from the reductase to the intact cytochrome can be markedly stimulated by detergents or phospholipids, which also cause profound enhancement of the NADH-cytochrome c reductase activity reconstituted from the reducatse and cytochrome b5. Upon digestion with trypsin [EC 3.4.21.4], the ability of the reductase to form an active NADH-cytochrome c reductase system with the intact form of cytochrome b5 and Triton X-100 is rapidly lost. This loss of the reconstitution capability can be prevented by preincubation of the reductase with phosphatidylcholine liposomes. Trypsin digestion also results in the cleavage of the reductase molecule to a protein having a molecular weight of about 25,000 and a smaller fragment. The purified flavoprotein can bind to liver microsomes, liver mitochondria, sonicated human erythrocyte ghosts, and phosphatidylcholine liposomes. The reductase solubilized directly from liver microsomes by lysosomal digestion however, is devoid of membrane-binding capacity. It is concluded that the intact form of NADH-cytochrome b5 reductase is an amphipathic protein and its hydrophobic moiety, which is removable by lysosomal digestion, is responsible for the tight binding of the reductase to microsomes and for its normal functioning in the membrane.", "contents": "Purification and properties of the intact form of NADH-cytochrome b5 reductase from rabbit liver microsomes. NADH-cytochrome b5 reductase [EC 1.6.2.2] has been solubilized with Triton X-100 and purified to homogeneity from rabbit liver microsomes. The purified enzyme is essentially free of the detergent and phospholipids and exists in aqueous media as an oligomeric aggregate of about 13 S. Its monomeric molecular weight is about 33,000 and 1 mole of FAD is associated with 1 mole of the monomeric unit. The enzyme catalyzes the reductions by NADH of ferricyanide and 2,6-dichlorophenol indophenol at an activity ratio of 1 : 0.09. Although the intact form of cytochrome b5 is a poorer electron acceptor than its hydrophilic fragment for the purified flavoprotein, electron transfer from the reductase to the intact cytochrome can be markedly stimulated by detergents or phospholipids, which also cause profound enhancement of the NADH-cytochrome c reductase activity reconstituted from the reducatse and cytochrome b5. Upon digestion with trypsin [EC 3.4.21.4], the ability of the reductase to form an active NADH-cytochrome c reductase system with the intact form of cytochrome b5 and Triton X-100 is rapidly lost. This loss of the reconstitution capability can be prevented by preincubation of the reductase with phosphatidylcholine liposomes. Trypsin digestion also results in the cleavage of the reductase molecule to a protein having a molecular weight of about 25,000 and a smaller fragment. The purified flavoprotein can bind to liver microsomes, liver mitochondria, sonicated human erythrocyte ghosts, and phosphatidylcholine liposomes. The reductase solubilized directly from liver microsomes by lysosomal digestion however, is devoid of membrane-binding capacity. It is concluded that the intact form of NADH-cytochrome b5 reductase is an amphipathic protein and its hydrophobic moiety, which is removable by lysosomal digestion, is responsible for the tight binding of the reductase to microsomes and for its normal functioning in the membrane."} {"id": "PMID:175050", "title": "Biochemical studies on sulfate-reducing bacteria. XIV. Enzyme levels of adenylylsulfate reductase, inorganic pyrophosphatase, sulfite reductase, hydrogenase, and adenosine triphosphatase in cells grown on sulfate, sulfite, and thiosulfate.", "content": "Sulfate-reducing bacteria, Desulfovibrio vulgaris, strain Miyazaki, were grown on either sulfate, sulfite, or thiosulfate as the terminal electron acceptor. Better growth was observed on sulfite and less growth on thiosulfate than on sulfate. Enzyme levels of adenylylsulfate (APS) reductase [EC 1.8.99.2], reductant-activated inorganic pyrophosphatase [EC 3.6.1.1], sulfite reductase [EC 1.8.99.1] (desulfoviridin), hydrogenase [EC 1.12.2.1], and Mg2+-activated ATPase [EC 3.6.1.3] were compared in crude extracts of these cells at various stages of growth. 1) The specific activity of APS reductase in sulfite-grown cells was only one-fourth that in sulfate-grown cells throughout growth. Thiosulfate-grown cells had an activity intermediate between those of sulfate- and sulfite-grown cells. 2) Cells grown on sulfite had lower specific activity of reductant-activated inorganic pyrophosphatase than cells grown on sulfate or thiosulfate. 3) The specific activity of sulfite reductase (desulfoviridin) was highest in sulfite-grown cells. The sulfite medium gave the enzyme in high yield as well as with high specific activity. 4) The specific activities of hydrogenase and Mg2+-ATPase were not significantly altered by electron acceptors in the growth medium.", "contents": "Biochemical studies on sulfate-reducing bacteria. XIV. Enzyme levels of adenylylsulfate reductase, inorganic pyrophosphatase, sulfite reductase, hydrogenase, and adenosine triphosphatase in cells grown on sulfate, sulfite, and thiosulfate. Sulfate-reducing bacteria, Desulfovibrio vulgaris, strain Miyazaki, were grown on either sulfate, sulfite, or thiosulfate as the terminal electron acceptor. Better growth was observed on sulfite and less growth on thiosulfate than on sulfate. Enzyme levels of adenylylsulfate (APS) reductase [EC 1.8.99.2], reductant-activated inorganic pyrophosphatase [EC 3.6.1.1], sulfite reductase [EC 1.8.99.1] (desulfoviridin), hydrogenase [EC 1.12.2.1], and Mg2+-activated ATPase [EC 3.6.1.3] were compared in crude extracts of these cells at various stages of growth. 1) The specific activity of APS reductase in sulfite-grown cells was only one-fourth that in sulfate-grown cells throughout growth. Thiosulfate-grown cells had an activity intermediate between those of sulfate- and sulfite-grown cells. 2) Cells grown on sulfite had lower specific activity of reductant-activated inorganic pyrophosphatase than cells grown on sulfate or thiosulfate. 3) The specific activity of sulfite reductase (desulfoviridin) was highest in sulfite-grown cells. The sulfite medium gave the enzyme in high yield as well as with high specific activity. 4) The specific activities of hydrogenase and Mg2+-ATPase were not significantly altered by electron acceptors in the growth medium."} {"id": "PMID:175051", "title": "Effect of glucose and cyclic adenosine 3',5'-monophosphate on the synthesis of succinate dehydrogenase and isocitrate lyase in Escherichia coli.", "content": "Repressed respiration of Escherichia coli cells grown in the presence of 2% glucose was derepressed when the cells were incubated in a buffer containing casamino acids. The glucose-repressed cells were deficient in succinate dehydrogenase [EC 1.3.99.1] and isocitrate lyase [EC 4.1.3.1] activities, which increased during the incubation. The increases in respiratory activity and enzyme activity on incubation were repressed by glucose, but except for isocitrate lyase these repressions could be restored by the addition of cyclic adenosine 3',5'-monophosphate. Inhibitors of protein synthesis blocked the increase of enzyme activity on incubation without glucose, or with glucose and the cyclic nucleotide.", "contents": "Effect of glucose and cyclic adenosine 3',5'-monophosphate on the synthesis of succinate dehydrogenase and isocitrate lyase in Escherichia coli. Repressed respiration of Escherichia coli cells grown in the presence of 2% glucose was derepressed when the cells were incubated in a buffer containing casamino acids. The glucose-repressed cells were deficient in succinate dehydrogenase [EC 1.3.99.1] and isocitrate lyase [EC 4.1.3.1] activities, which increased during the incubation. The increases in respiratory activity and enzyme activity on incubation were repressed by glucose, but except for isocitrate lyase these repressions could be restored by the addition of cyclic adenosine 3',5'-monophosphate. Inhibitors of protein synthesis blocked the increase of enzyme activity on incubation without glucose, or with glucose and the cyclic nucleotide."} {"id": "PMID:175052", "title": "The isolation and characterization of glycopeptides and mucopolysaccharides from plasma membranes of an ascites hepatoma, AH 130.", "content": "Plasma membranes were isolated from an ascites hepatoma, AH 130, by the fluorescein mercuric acetate (FMA) method. Glycopeptides and mucopolysaccharides were prepared by digesting the membranes with pronase, then by fractionating the digest chromatographically and electrophoretically. Isolated fractions were analyzed for their amino acid and carbohydrate compositions. Results were compared with those for corresponding fractions from AH 66 (J. Biochem. 76, 319-333 (1974)). Mucopolysaccharides and a series of glycopeptides were isolated from the fraction excluded from Sephadex G-50. The mucopolysaccharides were identified as a family of heparan sulfates with different electrophoretic mobilities. The glycopeptides contained serine, threonine, galactose, galactosamine, glucosamine, and sialic acid as the major constituents as aspartic acid and mannose as minor ones. This suggests that most of the carbohydrate moieties are linked to serine or threonine (O-glycosidic), and that some are linked to asparagine (N-glycosidic). No nearly purely O-glycosidic glycopeptides were found in this fraction from AH 130, through they were the major glycopeptides from the AH 66 plasma membranes. In the fraction included in the gel, glycopeptides containing fucose, galactose, mannose, glucosamine, glaactosamine, and sialic acid were found. The presence of galactosamine suggests that some of the glycopeptides are O-glycosidic though most are N-glycosidic. In the corresponding fraction from AH 66, nearly purely N-glycosidic glycopeptides were found.", "contents": "The isolation and characterization of glycopeptides and mucopolysaccharides from plasma membranes of an ascites hepatoma, AH 130. Plasma membranes were isolated from an ascites hepatoma, AH 130, by the fluorescein mercuric acetate (FMA) method. Glycopeptides and mucopolysaccharides were prepared by digesting the membranes with pronase, then by fractionating the digest chromatographically and electrophoretically. Isolated fractions were analyzed for their amino acid and carbohydrate compositions. Results were compared with those for corresponding fractions from AH 66 (J. Biochem. 76, 319-333 (1974)). Mucopolysaccharides and a series of glycopeptides were isolated from the fraction excluded from Sephadex G-50. The mucopolysaccharides were identified as a family of heparan sulfates with different electrophoretic mobilities. The glycopeptides contained serine, threonine, galactose, galactosamine, glucosamine, and sialic acid as the major constituents as aspartic acid and mannose as minor ones. This suggests that most of the carbohydrate moieties are linked to serine or threonine (O-glycosidic), and that some are linked to asparagine (N-glycosidic). No nearly purely O-glycosidic glycopeptides were found in this fraction from AH 130, through they were the major glycopeptides from the AH 66 plasma membranes. In the fraction included in the gel, glycopeptides containing fucose, galactose, mannose, glucosamine, glaactosamine, and sialic acid were found. The presence of galactosamine suggests that some of the glycopeptides are O-glycosidic though most are N-glycosidic. In the corresponding fraction from AH 66, nearly purely N-glycosidic glycopeptides were found."} {"id": "PMID:175053", "title": "Action of bacterial collagenase on Ascaris cuticle collagen.", "content": "The collagen from the cuticle of Ascaris lumbricoides was digested by Clostridium histolyticum collagenase [EC 3.4.24.3] in the presence and absence of CaCl2. About 1.2 mumoles of amino groups per mg collagen was liberated when the digestion was performed in the presence of 5 mM CaCl2, whereas about 0.5 mumole of amino groups per mg collagen was liberated by digestion in the absence of CaCl2. In contrast, CaCl2 influenced the extent of hydrolysis of rat tail tendon collagen only slightly. The results suggest that CaCl2 is necessary for the hydrolysis of certain regions in the molecule of Ascaris collagen and that such structures may not be present in mammalian collagens.", "contents": "Action of bacterial collagenase on Ascaris cuticle collagen. The collagen from the cuticle of Ascaris lumbricoides was digested by Clostridium histolyticum collagenase [EC 3.4.24.3] in the presence and absence of CaCl2. About 1.2 mumoles of amino groups per mg collagen was liberated when the digestion was performed in the presence of 5 mM CaCl2, whereas about 0.5 mumole of amino groups per mg collagen was liberated by digestion in the absence of CaCl2. In contrast, CaCl2 influenced the extent of hydrolysis of rat tail tendon collagen only slightly. The results suggest that CaCl2 is necessary for the hydrolysis of certain regions in the molecule of Ascaris collagen and that such structures may not be present in mammalian collagens."} {"id": "PMID:175054", "title": "Studies on a thermophilic RNA polymerase which is active only on poly d(A-T) and poly dAdT.", "content": "Two types of RNA polymerases [EC 2.7.7.6], polymerases A and B, exist in thermophilic bacteria, Thermus thermophilus HB8. Polymerase B is apparently like the core enzyme of polymerase A but is active only when an alternating copolymer of deoxyadenylic and deoxythymidylic acids (poly d(A-T)) or a mixture of homopolymers of deoxyadenylic acid and deoxythymidylic acid (poly dAdT) is used as a template. Polymerase B was further characterized to elucidate its relation to polymerase A and to determine why it is inactive on natural DNA's. 1. Polymerase B did not show pyrophosphate exchange activity. Dinucleoside monophosphates did not activate the RNA-synthesizing activity. The results suggested that polymerase B had no initiation and presumably no elongation activities. 2. Polymerase B had about 6 times greater affinity to DNA than polymerase A. The binding of polymerase B to DNA was, however, reversible. The complex of DNA with polymerase A was stable and the polymerase was not removed from the initial complex even when a large amount of DNA was added. 3. E. coli sigma subunit could not stimulate the activity of polymerase B toward DNA's. 4. Polymerase B could utilize poly d(A-T) and poly dAdT as templates, but could not use Bacillus cereus DNA though the structure is reported to be similar to that of poly d(A-T).", "contents": "Studies on a thermophilic RNA polymerase which is active only on poly d(A-T) and poly dAdT. Two types of RNA polymerases [EC 2.7.7.6], polymerases A and B, exist in thermophilic bacteria, Thermus thermophilus HB8. Polymerase B is apparently like the core enzyme of polymerase A but is active only when an alternating copolymer of deoxyadenylic and deoxythymidylic acids (poly d(A-T)) or a mixture of homopolymers of deoxyadenylic acid and deoxythymidylic acid (poly dAdT) is used as a template. Polymerase B was further characterized to elucidate its relation to polymerase A and to determine why it is inactive on natural DNA's. 1. Polymerase B did not show pyrophosphate exchange activity. Dinucleoside monophosphates did not activate the RNA-synthesizing activity. The results suggested that polymerase B had no initiation and presumably no elongation activities. 2. Polymerase B had about 6 times greater affinity to DNA than polymerase A. The binding of polymerase B to DNA was, however, reversible. The complex of DNA with polymerase A was stable and the polymerase was not removed from the initial complex even when a large amount of DNA was added. 3. E. coli sigma subunit could not stimulate the activity of polymerase B toward DNA's. 4. Polymerase B could utilize poly d(A-T) and poly dAdT as templates, but could not use Bacillus cereus DNA though the structure is reported to be similar to that of poly d(A-T)."} {"id": "PMID:175055", "title": "Effect of alcohols on polypeptide chain elongation and aminoacyl-tRNA formation.", "content": "The effect of alcohols (methanol, ethanol, and propanol) on polypeptide chain elongation was studied. In the E. coli and rat liver cell-free systems, the optimal concentration of Mg2+ decreased with increase of ethanol concentration, although the maximum polyphenylalanine synthesis decreased. Methanol had almost the same effect as ethanol. Propanol decreased the optimal magnesium concentration, but polyphenylalanine synthetic activity was markedly decreased. The shift of optimal Mg2+ concentration by ethanol was also observed in polylysine and polysome-dependent polypeptide syntheses. Even in the presence of spermidine, ethanol caused the shift of optimal Mg2+ concentration. Ribosome-bound Mg2+ was decreased by the addition of ethanol. A study of the effect of alcohols on aminoacyl-tRNA formation with ten amino acids in the absence of added Mg2+ showed that the formation of arginyl-, leucyl-, and valyl-tRNA was stimulated by the alcohols. Valyl-tRNA formation in the presence of alcohols was completely inhibited by EDTA, while that in the presence of Mg2+ was inhibited slightly by EDTA. No PP1-ATP exchange was observed when alcohol was used as the only stimulant of valyl-tRNA formation.", "contents": "Effect of alcohols on polypeptide chain elongation and aminoacyl-tRNA formation. The effect of alcohols (methanol, ethanol, and propanol) on polypeptide chain elongation was studied. In the E. coli and rat liver cell-free systems, the optimal concentration of Mg2+ decreased with increase of ethanol concentration, although the maximum polyphenylalanine synthesis decreased. Methanol had almost the same effect as ethanol. Propanol decreased the optimal magnesium concentration, but polyphenylalanine synthetic activity was markedly decreased. The shift of optimal Mg2+ concentration by ethanol was also observed in polylysine and polysome-dependent polypeptide syntheses. Even in the presence of spermidine, ethanol caused the shift of optimal Mg2+ concentration. Ribosome-bound Mg2+ was decreased by the addition of ethanol. A study of the effect of alcohols on aminoacyl-tRNA formation with ten amino acids in the absence of added Mg2+ showed that the formation of arginyl-, leucyl-, and valyl-tRNA was stimulated by the alcohols. Valyl-tRNA formation in the presence of alcohols was completely inhibited by EDTA, while that in the presence of Mg2+ was inhibited slightly by EDTA. No PP1-ATP exchange was observed when alcohol was used as the only stimulant of valyl-tRNA formation."} {"id": "PMID:175056", "title": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 3. Synthesis of deoxyribopolynucleotide segments corresponding to the nucleotide sequence 27-51.", "content": "Chemical syntheses of the four deoxyribodecanucleotides, d(T-C-G-A-A-G-T-C-G-A), d(C-G-T-C-A-T-C-G-A-C), d(T-G-A-C-G-G-C-A-G-A), and d(C-T-A-A-A-T-C-T-G-C) are described. These polynucleotides form, respectively, segments 7 to 10 in the plan adopted for the total synthesis of the DNA corresponding to the precursor for the Escherichia coli tyrosine tRNA. The syntheses used the principles of stepwise addition of protected mono- and oligonucleotides to the 3'-hydroxyl end of growing oligonucleotide chains. Detailed schemes used in the present syntheses are shown in Diagrams 1 to 4 in the text. The final products were subjected to extensive chromatography and were characterized as pure by chemical and enzymatic procedures.", "contents": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 3. Synthesis of deoxyribopolynucleotide segments corresponding to the nucleotide sequence 27-51. Chemical syntheses of the four deoxyribodecanucleotides, d(T-C-G-A-A-G-T-C-G-A), d(C-G-T-C-A-T-C-G-A-C), d(T-G-A-C-G-G-C-A-G-A), and d(C-T-A-A-A-T-C-T-G-C) are described. These polynucleotides form, respectively, segments 7 to 10 in the plan adopted for the total synthesis of the DNA corresponding to the precursor for the Escherichia coli tyrosine tRNA. The syntheses used the principles of stepwise addition of protected mono- and oligonucleotides to the 3'-hydroxyl end of growing oligonucleotide chains. Detailed schemes used in the present syntheses are shown in Diagrams 1 to 4 in the text. The final products were subjected to extensive chromatography and were characterized as pure by chemical and enzymatic procedures."} {"id": "PMID:175057", "title": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 10. Enzymatic joining of chemically synthesized segments to form the DNA duplex corresponding to the nucleotide sequence 86-126.", "content": "The polynucleotide ligase-catalyzed joining of the eight chemically synthesized deoxypolynucleotides (segments 19 to 26), comprising the nucleotide sequence 86-126 of the DNA corresponding to the Escherichia coli tyrosine tRNA precursor has been investigated. Joining was studied using various combinations of 3, 4, or larger number of segments at a time. The extent of joining was in general low (0 to 40%) for the three-component as well as for the four-component systems. Joining of the five- and six- component systems was more satisfactory with yields from 25 to about 60%. The three duplexes [IVa] to [IVc]were prepared in single step reactions in yields of about 50% and were characterized. Duplex [IVd] could not be prepared in a single step reaction because of the failure of 5'-phosphorylated segment 26 to join to the rest of the duplex. Using a carefully annealed mixture of segments 24, 25, and phosphorylated segment 26, the joining of the latter to segment 24 could be realized in about 25% yield, much activated intermediate being concurrently present.", "contents": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 10. Enzymatic joining of chemically synthesized segments to form the DNA duplex corresponding to the nucleotide sequence 86-126. The polynucleotide ligase-catalyzed joining of the eight chemically synthesized deoxypolynucleotides (segments 19 to 26), comprising the nucleotide sequence 86-126 of the DNA corresponding to the Escherichia coli tyrosine tRNA precursor has been investigated. Joining was studied using various combinations of 3, 4, or larger number of segments at a time. The extent of joining was in general low (0 to 40%) for the three-component as well as for the four-component systems. Joining of the five- and six- component systems was more satisfactory with yields from 25 to about 60%. The three duplexes [IVa] to [IVc]were prepared in single step reactions in yields of about 50% and were characterized. Duplex [IVd] could not be prepared in a single step reaction because of the failure of 5'-phosphorylated segment 26 to join to the rest of the duplex. Using a carefully annealed mixture of segments 24, 25, and phosphorylated segment 26, the joining of the latter to segment 24 could be realized in about 25% yield, much activated intermediate being concurrently present."} {"id": "PMID:175058", "title": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 11. Enzymatic joining to form the total DNA duplex.", "content": "The DNA duplex corresponding to the entire length (126 nucleotides) of the precursor for an Escherichia coli tyrosine tRNA has been synthesized. Duplex [I] (Sekiya, T., Besmer, P., Takeya, T., and Khorana, H. G.(1976) J. Biol. Chem. 251, 634-641), corresponding to the nucleotide sequence 1-26, containing single-stranded ends and carrying one appropriately labeled 5'-phosphate group, was joined to duplex [II] (Loewen, P. C., Miller, R. C., Panet, A., Sekiya, T., and Khorana, H. G. (1976) J. Biol. Chem. 251, 642-650) (nucleotide sequence 23-66 or 23-60) was phosphorylated with [gamma-33P]ATP at the 5'-OH ends. Duplex [III] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H. G. (1976) J. Biol. Chem. 251, 651-657) (nucleotide sequence 57-94 (Fig. 2)) was also phosphorylated at 5'-ends with [gamma-33P]ATP and was joined to duplex [IV] (Caruthers, M. H., Kleppe, R., Kleppe, K., and Khorana, H. G. (1976) J. Biol. Chem. 251, 658-666) (nucleotide sequence 90-126) which carried a 33P-labeled phosphate group on nucleotide 90. The joined product, duplex [III + IV] (nucleotide sequence 57-126) was characterized. The latter duplex was joined to the duplex [I + II] to give the total duplex. The latter contains singlestranded ends (nucleotides 1 to 6 and 121 to 126) which can either be \"filled in\" to produce the completely base-paired duplex or may be used to add the promoter and terminator regions at the appropriate ends.", "contents": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 11. Enzymatic joining to form the total DNA duplex. The DNA duplex corresponding to the entire length (126 nucleotides) of the precursor for an Escherichia coli tyrosine tRNA has been synthesized. Duplex [I] (Sekiya, T., Besmer, P., Takeya, T., and Khorana, H. G.(1976) J. Biol. Chem. 251, 634-641), corresponding to the nucleotide sequence 1-26, containing single-stranded ends and carrying one appropriately labeled 5'-phosphate group, was joined to duplex [II] (Loewen, P. C., Miller, R. C., Panet, A., Sekiya, T., and Khorana, H. G. (1976) J. Biol. Chem. 251, 642-650) (nucleotide sequence 23-66 or 23-60) was phosphorylated with [gamma-33P]ATP at the 5'-OH ends. Duplex [III] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H. G. (1976) J. Biol. Chem. 251, 651-657) (nucleotide sequence 57-94 (Fig. 2)) was also phosphorylated at 5'-ends with [gamma-33P]ATP and was joined to duplex [IV] (Caruthers, M. H., Kleppe, R., Kleppe, K., and Khorana, H. G. (1976) J. Biol. Chem. 251, 658-666) (nucleotide sequence 90-126) which carried a 33P-labeled phosphate group on nucleotide 90. The joined product, duplex [III + IV] (nucleotide sequence 57-126) was characterized. The latter duplex was joined to the duplex [I + II] to give the total duplex. The latter contains singlestranded ends (nucleotides 1 to 6 and 121 to 126) which can either be \"filled in\" to produce the completely base-paired duplex or may be used to add the promoter and terminator regions at the appropriate ends."} {"id": "PMID:175059", "title": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 12. Synthesis of a DNA duplex corresponding to a sequence of 23 nucleotide units adjoining the C-C-A end.", "content": "In continuing the work on the total synthesis of the gene for an Escherichia coli tyrosine suppressor tRNA (accompanying papers) and as a part of a study of the mechanism of transcription of this gene, a 23-nucleotide unit-long DNA corresponding to the previously determined (Loewen, P., Sekiya, T., and Khorana, H. G. (1974) J. Biol. Chem. 249, 217) sequence has been synthesized. The synthesis was carried out by dividing the total duplex into the following five deoxyribooligonucleotide segments, all of which were chemically synthesized: (a) the undecanucleotide, d(A-G-T-G-A-T-G-G-T-G-G); (b)the undecanucleotide, d(T-C-A-C-T-T-T-C-A-A-A); (c) the undecanucleotide, d(G-G-A-C-T-T-T-T-G-A-A); (d) the dodecanucleotide, d(A-G-T-C-C-C-T-G-A-A-C-T); and (e) the heptanucleotide, d(A-G-T-T-C-A-G). All the five synthetic oligonucleotides were characterized by chromatographic and radioactive fingerprinting methods after labeling the 5'-ends with a 32P-phosphate group. Synthesis of the double-stranded DNA duplex was completed by joining 5'-phosphorylated segments 1, 3, and 4 in the presence of segments 2 and 5 using T4-polynucleotide ligase. The DNA duplex was characterized.", "contents": "Total synthesis of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli. 12. Synthesis of a DNA duplex corresponding to a sequence of 23 nucleotide units adjoining the C-C-A end. In continuing the work on the total synthesis of the gene for an Escherichia coli tyrosine suppressor tRNA (accompanying papers) and as a part of a study of the mechanism of transcription of this gene, a 23-nucleotide unit-long DNA corresponding to the previously determined (Loewen, P., Sekiya, T., and Khorana, H. G. (1974) J. Biol. Chem. 249, 217) sequence has been synthesized. The synthesis was carried out by dividing the total duplex into the following five deoxyribooligonucleotide segments, all of which were chemically synthesized: (a) the undecanucleotide, d(A-G-T-G-A-T-G-G-T-G-G); (b)the undecanucleotide, d(T-C-A-C-T-T-T-C-A-A-A); (c) the undecanucleotide, d(G-G-A-C-T-T-T-T-G-A-A); (d) the dodecanucleotide, d(A-G-T-C-C-C-T-G-A-A-C-T); and (e) the heptanucleotide, d(A-G-T-T-C-A-G). All the five synthetic oligonucleotides were characterized by chromatographic and radioactive fingerprinting methods after labeling the 5'-ends with a 32P-phosphate group. Synthesis of the double-stranded DNA duplex was completed by joining 5'-phosphorylated segments 1, 3, and 4 in the presence of segments 2 and 5 using T4-polynucleotide ligase. The DNA duplex was characterized."} {"id": "PMID:175060", "title": "Effects of adenosine 3':5'-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting skeletal muscles.", "content": "Effects of cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase were studied in sarcoplasmic reticulum prepared from cardiac and slow and fast (white) skeletal muscle. Cyclic AMP-dependent protein kinase failed to catalyze phosphorylation of fast skeletal muscle microsomes as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cyclic AMP-dependent protein kinase was without effect on calcium uptake by these microsomes. Treatment of cardiac microsomes obtained from dog, cat, rabbit, and guinea pig with cyclic AMP-dependent protein kinase and ATP resulted in phosphorylation of a 22,000-dalton protein component in the amounts of 0.75, 0.25, 0.30, and 0.14 nmol of phosphorus/mg of microsomal protein, respectively. Calcium uptake by cardiac microsomes was stimulated 1.8- to 2.5-fold when microsomes were treated with cyclic AMP-dependent protein kinase. Protein kinases partially purified from bovine heart and rabbit skeletal muscle were both effective in mediating these effects on phosphorylation and calcium transport in dog cardiac sarcoplasmic reticulum. Slow skeletal muscle sarcoplasmic reticulum also contains a protein with a molecular weight of approximately 22,000 that can be phosphorylated by protein kinase. Phosphorylation of this component ranged from 0.005 to 0.016 nmol of phosphorous/mg of microsomal protein in dog biceps femoris. A statistically significant increase in calcium uptake by these membranes was produced by the protein kinase. Increases in protein kinase-catalyzed phosphorylation of a low molecular weight microsomal component and in calcium transport by sarcoplasmic reticulum of cardiac and slow skeletal muscle may be related to the relaxation-promoting effects of epinephrine seen in these types of muscle. Conversely, the absence of a relaxation-promoting effect of epinephrine in fast skeletal muscle may be associated with the lack of effect of cyclic AMP and protein kinase on calcium transport by the sarcoplasmic reticulum of this type of muscle.", "contents": "Effects of adenosine 3':5'-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting skeletal muscles. Effects of cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase were studied in sarcoplasmic reticulum prepared from cardiac and slow and fast (white) skeletal muscle. Cyclic AMP-dependent protein kinase failed to catalyze phosphorylation of fast skeletal muscle microsomes as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cyclic AMP-dependent protein kinase was without effect on calcium uptake by these microsomes. Treatment of cardiac microsomes obtained from dog, cat, rabbit, and guinea pig with cyclic AMP-dependent protein kinase and ATP resulted in phosphorylation of a 22,000-dalton protein component in the amounts of 0.75, 0.25, 0.30, and 0.14 nmol of phosphorus/mg of microsomal protein, respectively. Calcium uptake by cardiac microsomes was stimulated 1.8- to 2.5-fold when microsomes were treated with cyclic AMP-dependent protein kinase. Protein kinases partially purified from bovine heart and rabbit skeletal muscle were both effective in mediating these effects on phosphorylation and calcium transport in dog cardiac sarcoplasmic reticulum. Slow skeletal muscle sarcoplasmic reticulum also contains a protein with a molecular weight of approximately 22,000 that can be phosphorylated by protein kinase. Phosphorylation of this component ranged from 0.005 to 0.016 nmol of phosphorous/mg of microsomal protein in dog biceps femoris. A statistically significant increase in calcium uptake by these membranes was produced by the protein kinase. Increases in protein kinase-catalyzed phosphorylation of a low molecular weight microsomal component and in calcium transport by sarcoplasmic reticulum of cardiac and slow skeletal muscle may be related to the relaxation-promoting effects of epinephrine seen in these types of muscle. Conversely, the absence of a relaxation-promoting effect of epinephrine in fast skeletal muscle may be associated with the lack of effect of cyclic AMP and protein kinase on calcium transport by the sarcoplasmic reticulum of this type of muscle."} {"id": "PMID:175061", "title": "Adenine nucleotide changes at initiation of bull sperm motility.", "content": "Testicular and cauda epididymal sperm were obtained via catheters previously implanted in the rete testis and proximal vas deferens of bulls and were used to examine the relationships among sperm motility, cyclic adenosine 3':5'-monophosphate (cAMP) level, adenine nucleotide levels, and rates of glucose and oxygen consumption. Testicular, cauda epididymal, and ejaculated sperm contain cAMP-stimulated protein kinase, adenylate cyclase, and nucleotide phosphodiesterase. Treatment of the nonmotile testicular sperm with phosphodiesterase inhibitors resulted in a doubling of cellular cAMP concentration and a 25% increase in their glucose consumption. No change in motility, ATP level, or rate of oxygen consumption was observed. Sperm in neat cauda epididymal semen had flagellating tails but no progressive motility. Dilution of these sperm into glucose-containing buffer resulted in an increase in intracellular cAMP concentration and a decrease in ATP level with concomitant increases in ADP and AMP levels. These biochemical changes occurred within 30 s after dilution and apparently preceded the initiation of progressive motility by most cells. Since sperm in neat cauda epididymal semen became progressively motile when diluted with neat cauda epididymal plasma as well as accessory sex gland fluid or buffer, composition of the fluid surrounding the sperm is not responsible for the initiation of progressive motility upon dilution nor does cauda epididymal plasma contain an inhibitory factor. Perhaps release from contact immobilization provides the stimulation for the initial acquisition of progressive motility by cauda epididymal sperm. We conclude that during epididymal passage sperm develop from a cell physically unresponsive to changes in cAMP concentration to a form which initiates progressive motility upon changes in cAMP concentration.", "contents": "Adenine nucleotide changes at initiation of bull sperm motility. Testicular and cauda epididymal sperm were obtained via catheters previously implanted in the rete testis and proximal vas deferens of bulls and were used to examine the relationships among sperm motility, cyclic adenosine 3':5'-monophosphate (cAMP) level, adenine nucleotide levels, and rates of glucose and oxygen consumption. Testicular, cauda epididymal, and ejaculated sperm contain cAMP-stimulated protein kinase, adenylate cyclase, and nucleotide phosphodiesterase. Treatment of the nonmotile testicular sperm with phosphodiesterase inhibitors resulted in a doubling of cellular cAMP concentration and a 25% increase in their glucose consumption. No change in motility, ATP level, or rate of oxygen consumption was observed. Sperm in neat cauda epididymal semen had flagellating tails but no progressive motility. Dilution of these sperm into glucose-containing buffer resulted in an increase in intracellular cAMP concentration and a decrease in ATP level with concomitant increases in ADP and AMP levels. These biochemical changes occurred within 30 s after dilution and apparently preceded the initiation of progressive motility by most cells. Since sperm in neat cauda epididymal semen became progressively motile when diluted with neat cauda epididymal plasma as well as accessory sex gland fluid or buffer, composition of the fluid surrounding the sperm is not responsible for the initiation of progressive motility upon dilution nor does cauda epididymal plasma contain an inhibitory factor. Perhaps release from contact immobilization provides the stimulation for the initial acquisition of progressive motility by cauda epididymal sperm. We conclude that during epididymal passage sperm develop from a cell physically unresponsive to changes in cAMP concentration to a form which initiates progressive motility upon changes in cAMP concentration."} {"id": "PMID:175062", "title": "Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release.", "content": "Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.", "contents": "Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation."} {"id": "PMID:175063", "title": "Turnover of the plasma membrane proteins of hepatoma tissue culture cells.", "content": "The turnover of the plasma membrane proteins of hepatoma tissue culture cells was examined by three different methods--loss of polypeptides labeled in situ by lactoperoxidase-catalyzed iodination, loss of membrane polypeptides labeled with amino acid precursors, and loss from the membrane of fucose-labeled polypeptides. In both logarithmically growing and density-inhibited cells the proteins of the membrane are degraded with a half-life of about 100 hours. This is longer than the half-life of total cell protein, 50 to 60 hours, and longer than the doubling time of the cells, about 30 hours. Similar values for the rate of degradation of the membrane proteins were obtained by each of the three techniques. The same fucose-labeled polypeptides are present in the microsomal and the plasma membrane fractions of hepatoma tissue culture cells as analyzed by electrophoresis in dodecyl sulfate-acrylamide gels. But the fucose-labeled polypeptides were lost from the microsomal fraction at a faster rate than from the plasma membrane. Autoradiographic and double labeling techniques using 125I and 131I, or [3H]leucine and [14C]leucine were used to measure the relative rates of degradation of the proteins in the plasma membrane. All of the leucine-labeled polypeptides and the iodinated polypeptides had similar rates of degradation. These results support a model for the biogenesis of the plasma membrane in which the proteins are incorporated and removed in large structural units.", "contents": "Turnover of the plasma membrane proteins of hepatoma tissue culture cells. The turnover of the plasma membrane proteins of hepatoma tissue culture cells was examined by three different methods--loss of polypeptides labeled in situ by lactoperoxidase-catalyzed iodination, loss of membrane polypeptides labeled with amino acid precursors, and loss from the membrane of fucose-labeled polypeptides. In both logarithmically growing and density-inhibited cells the proteins of the membrane are degraded with a half-life of about 100 hours. This is longer than the half-life of total cell protein, 50 to 60 hours, and longer than the doubling time of the cells, about 30 hours. Similar values for the rate of degradation of the membrane proteins were obtained by each of the three techniques. The same fucose-labeled polypeptides are present in the microsomal and the plasma membrane fractions of hepatoma tissue culture cells as analyzed by electrophoresis in dodecyl sulfate-acrylamide gels. But the fucose-labeled polypeptides were lost from the microsomal fraction at a faster rate than from the plasma membrane. Autoradiographic and double labeling techniques using 125I and 131I, or [3H]leucine and [14C]leucine were used to measure the relative rates of degradation of the proteins in the plasma membrane. All of the leucine-labeled polypeptides and the iodinated polypeptides had similar rates of degradation. These results support a model for the biogenesis of the plasma membrane in which the proteins are incorporated and removed in large structural units."} {"id": "PMID:175064", "title": "Relationship between microsomal membrane permeability and the inhibition of hepatic glucose-6-phosphatase by pyridoxal phosphate.", "content": "Arion et al; (Arion, W. J., Wallin, B. K., Lange A. J., and Ballas, L. M. (1975) Mol. Cell. Biochem. 6, 75-83) propsed a model for glucose-6-phosphatase in which the substrate was transported across the microsomal membrane by a carrier before hydrolysis on the cisternal side. Evidence to support this model has been obtained by studying the inhibition of the enzyme by pyridoxal-P. Pyridoxal-P was a linear noncompetitive inhibitor of glucose-6-phosphatase (EC 3.1.3.9) in freshly isolated (\"intact\") microsomes from rat liver. Pyridoxol-P was a much less effective inhibitor and no inhibition was observed with pyridoxamine-P. When microsomes were subjected to nitrogen cavitation, treatment with solium deoxycholate, or glutaraldehyde fixation, the Km of glucose-6-phosphatase for glucose-6 P decreased from approximately 6 mM to approximately 2.5 mM; the corresponding change in the Vmax ranged from-10% to +40%. The same procedures decreased the inhibition of glucose-6-phosphatase by pyridoxal-P several-fold. No inhibition by pyridoxal-P was observed in a preparation of glucose-6-phosphatase purified approximately 20 fold (on the basis of Vmax) from micoromes. A nondialyzable inhibitor was apparently formed when intact microsomes were reacted with pyridoxal-P and NaBH4; this inhibition was also reversed by procedures which changed the kinetic properties of glucose-6-phosphatase.", "contents": "Relationship between microsomal membrane permeability and the inhibition of hepatic glucose-6-phosphatase by pyridoxal phosphate. Arion et al; (Arion, W. J., Wallin, B. K., Lange A. J., and Ballas, L. M. (1975) Mol. Cell. Biochem. 6, 75-83) propsed a model for glucose-6-phosphatase in which the substrate was transported across the microsomal membrane by a carrier before hydrolysis on the cisternal side. Evidence to support this model has been obtained by studying the inhibition of the enzyme by pyridoxal-P. Pyridoxal-P was a linear noncompetitive inhibitor of glucose-6-phosphatase (EC 3.1.3.9) in freshly isolated (\"intact\") microsomes from rat liver. Pyridoxol-P was a much less effective inhibitor and no inhibition was observed with pyridoxamine-P. When microsomes were subjected to nitrogen cavitation, treatment with solium deoxycholate, or glutaraldehyde fixation, the Km of glucose-6-phosphatase for glucose-6 P decreased from approximately 6 mM to approximately 2.5 mM; the corresponding change in the Vmax ranged from-10% to +40%. The same procedures decreased the inhibition of glucose-6-phosphatase by pyridoxal-P several-fold. No inhibition by pyridoxal-P was observed in a preparation of glucose-6-phosphatase purified approximately 20 fold (on the basis of Vmax) from micoromes. A nondialyzable inhibitor was apparently formed when intact microsomes were reacted with pyridoxal-P and NaBH4; this inhibition was also reversed by procedures which changed the kinetic properties of glucose-6-phosphatase."} {"id": "PMID:175065", "title": "Studies on human serum high density lipoproteins. Self-association of apolipoprotein A-I in aqueous solutions.", "content": "Human serum apolipoprotein A-I (apo-A-I), the major protein component of the human serum high density lipoproteins, was studied in aqueous solutions of differing ionic strength and pH by the techniques of sedimentation equilibrium ultracentrifugation and frontal analysis gel chromatography. The ultracentrifugal studies indicate the apo-A-I is a self-associating system that is dependent upon protein concentration, but relatively independent of the nature of the medium. The apparent weight average molecular weights obtained from solutions of initial apo-A-I concentration between 0.2 and 0.9 mg/ml were in the range of 3.0 to 16.7 x 10(4) (monomer molecular weight = 28,014). Of the several models of self-associated examined, that which gave the best theoretical fit was for the monomer-dimertetramer-octamer model. The self-association of apo-A-I in aqueous solutions was further documented by frontal analysis gel chromatography, which not only corroborated the ultracentrifugal results, but also indicated that the multiple species of apo-A-I in solution attain equilibrium rather rapidly. Besides having intrinsic importance, these results indicate that the solution properties of apo-A-I must be established before ligand binding studies are conducted and interpreted.", "contents": "Studies on human serum high density lipoproteins. Self-association of apolipoprotein A-I in aqueous solutions. Human serum apolipoprotein A-I (apo-A-I), the major protein component of the human serum high density lipoproteins, was studied in aqueous solutions of differing ionic strength and pH by the techniques of sedimentation equilibrium ultracentrifugation and frontal analysis gel chromatography. The ultracentrifugal studies indicate the apo-A-I is a self-associating system that is dependent upon protein concentration, but relatively independent of the nature of the medium. The apparent weight average molecular weights obtained from solutions of initial apo-A-I concentration between 0.2 and 0.9 mg/ml were in the range of 3.0 to 16.7 x 10(4) (monomer molecular weight = 28,014). Of the several models of self-associated examined, that which gave the best theoretical fit was for the monomer-dimertetramer-octamer model. The self-association of apo-A-I in aqueous solutions was further documented by frontal analysis gel chromatography, which not only corroborated the ultracentrifugal results, but also indicated that the multiple species of apo-A-I in solution attain equilibrium rather rapidly. Besides having intrinsic importance, these results indicate that the solution properties of apo-A-I must be established before ligand binding studies are conducted and interpreted."} {"id": "PMID:175066", "title": "Testicular protein kinases. Characterization of multiple forms and ontogeny.", "content": "Protein phosphokinase activity from the cytosol (105,000 X g soluble fraction) of testes from sexually mature rats has been resolved be DEAE-cellulose chromatography in three forms of protein kinase, cAMP-dependent protein kinases I and II and cAMP-independent protein kinase III. Adenosine 3':5'-monophosphate-binding activity (cAMP-binding activity) was associated with protein kinases I and II but not with protein kinase III. Protein kinases I, II, and III exhibited different pH optima, cyclic nucleotide dependency, and relative substrate specificity. Protein kinases I and II were inhibited by a heat-stable protein inhibitor from rat skeletal muscle, whereas protein kinase III was not inhibited. According to previously established criteria (Traugh, J. A., Ashby, C.D., and Walsh D. A. (1974) Methods Enzymol. 38, 290-299) protein kinases I and II can be classified as cAMP-dependent holoenzymes consisting of regulatory and catalytic subunits. Protein kinase III is a cAMP-independent protein kinase.", "contents": "Testicular protein kinases. Characterization of multiple forms and ontogeny. Protein phosphokinase activity from the cytosol (105,000 X g soluble fraction) of testes from sexually mature rats has been resolved be DEAE-cellulose chromatography in three forms of protein kinase, cAMP-dependent protein kinases I and II and cAMP-independent protein kinase III. Adenosine 3':5'-monophosphate-binding activity (cAMP-binding activity) was associated with protein kinases I and II but not with protein kinase III. Protein kinases I, II, and III exhibited different pH optima, cyclic nucleotide dependency, and relative substrate specificity. Protein kinases I and II were inhibited by a heat-stable protein inhibitor from rat skeletal muscle, whereas protein kinase III was not inhibited. According to previously established criteria (Traugh, J. A., Ashby, C.D., and Walsh D. A. (1974) Methods Enzymol. 38, 290-299) protein kinases I and II can be classified as cAMP-dependent holoenzymes consisting of regulatory and catalytic subunits. Protein kinase III is a cAMP-independent protein kinase."} {"id": "PMID:175067", "title": "ATP-dependent reactions catalyzed by inner membrane vesicles of rat liver mitochondria. Kinetics, substrate specificity, and bicarbonate sensitivity.", "content": "Three ATP-dependent reactions catalyzed by the inner membrane of rat liver mitochondria and the ATPase reaction catalyzed by purified mitochondrial ATPase (F1), were studied with respect to kinetic properties, substrates specificity, and sensitivity to bicarbonate. The ATP-dependent transhydrogenase reaction (reduction of NADP+ by NADH) catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers, with Km (ATP) values of 0.035 mM and 0.054 mM respectively. The Vmax of transhydrogenase activity (25 nmol min-1 mg-1) is the same in Tris-bicarbonate or Tris-Cl buffer. ITP and GTP readily substitute for ATP in the transhydrogenase reaction. The ATP-P1 exchange reaction catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers with Km (ATP) values of 1.0 mM and 1.4 mM respectively. The Vmax of exchange (200 nmol min-1 mg-1) is the same in either buffer. ITP and GTP do not effectively replace ATP in the exchange reaction.", "contents": "ATP-dependent reactions catalyzed by inner membrane vesicles of rat liver mitochondria. Kinetics, substrate specificity, and bicarbonate sensitivity. Three ATP-dependent reactions catalyzed by the inner membrane of rat liver mitochondria and the ATPase reaction catalyzed by purified mitochondrial ATPase (F1), were studied with respect to kinetic properties, substrates specificity, and sensitivity to bicarbonate. The ATP-dependent transhydrogenase reaction (reduction of NADP+ by NADH) catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers, with Km (ATP) values of 0.035 mM and 0.054 mM respectively. The Vmax of transhydrogenase activity (25 nmol min-1 mg-1) is the same in Tris-bicarbonate or Tris-Cl buffer. ITP and GTP readily substitute for ATP in the transhydrogenase reaction. The ATP-P1 exchange reaction catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers with Km (ATP) values of 1.0 mM and 1.4 mM respectively. The Vmax of exchange (200 nmol min-1 mg-1) is the same in either buffer. ITP and GTP do not effectively replace ATP in the exchange reaction."} {"id": "PMID:175068", "title": "A major polypeptide component of rat liver mitochondria: carbamyl phosphate synthetase.", "content": "One of the major components of rat liver mitochondria detected by gel electrophoresis in sodium dodecyl sulfate is a 165,000 molecular weight polypeptide that makes up 15 to 20% of the total mitochondrial protein. This component appears to be a single molecular species. Evidence is presented here for the identification of this protein with the polypeptide chain of a urea cycle enzyme, carbamoylphosphate synthetase I (EC 2.7.2.5). The 165,000 molecular weight polypeptide was solubilized from mitochondria with Triton X-100 and purified to 90% homogeneity by DEAE-cellulose chromatography. This component co-migrated with carbamyl phosphate synthetase activity when mitochondrial proteins were separated by gel filtration or sucrose gradient centifugation. The identification of the 165,000 molecular weight polypeptide with this activity was also supported by the presence or absence of this protein in a variety of rat tissue mitochondria, in liver and kidney mitochondria from various ureotelic and nonureotelic species, and in fetal rat liver mitochondria.", "contents": "A major polypeptide component of rat liver mitochondria: carbamyl phosphate synthetase. One of the major components of rat liver mitochondria detected by gel electrophoresis in sodium dodecyl sulfate is a 165,000 molecular weight polypeptide that makes up 15 to 20% of the total mitochondrial protein. This component appears to be a single molecular species. Evidence is presented here for the identification of this protein with the polypeptide chain of a urea cycle enzyme, carbamoylphosphate synthetase I (EC 2.7.2.5). The 165,000 molecular weight polypeptide was solubilized from mitochondria with Triton X-100 and purified to 90% homogeneity by DEAE-cellulose chromatography. This component co-migrated with carbamyl phosphate synthetase activity when mitochondrial proteins were separated by gel filtration or sucrose gradient centifugation. The identification of the 165,000 molecular weight polypeptide with this activity was also supported by the presence or absence of this protein in a variety of rat tissue mitochondria, in liver and kidney mitochondria from various ureotelic and nonureotelic species, and in fetal rat liver mitochondria."} {"id": "PMID:175069", "title": "In vitro bacteriological evaluation of the effectiveness of antimicrobial irrigating solutions.", "content": "Nineteen strains of pathogenic aerobic bacteria were exposed for fifteen seconds in vitro to varying concentrations of five antibiotics and of polyvinyl povidone iodine in saline solution. The presence of human plasma in the solution (30 per cent by volume) did not affect bacterial sensitivity to the antibiotics. Most of the bacteria were sensitive to the solutions during that brief exposure. Bacteria which were more sensitive by disc sensitivity tests were more sensitive to the solutions. Polyvinyl povidone iodine sterilized all cultures in concentrations as low as 25 per cent. It is proposed that the use of appropriate antimicrobial solutions as wound irrigants may reduce postoperative infection rates by killing bacteria which contaminate the surface of the wound during operation.", "contents": "In vitro bacteriological evaluation of the effectiveness of antimicrobial irrigating solutions. Nineteen strains of pathogenic aerobic bacteria were exposed for fifteen seconds in vitro to varying concentrations of five antibiotics and of polyvinyl povidone iodine in saline solution. The presence of human plasma in the solution (30 per cent by volume) did not affect bacterial sensitivity to the antibiotics. Most of the bacteria were sensitive to the solutions during that brief exposure. Bacteria which were more sensitive by disc sensitivity tests were more sensitive to the solutions. Polyvinyl povidone iodine sterilized all cultures in concentrations as low as 25 per cent. It is proposed that the use of appropriate antimicrobial solutions as wound irrigants may reduce postoperative infection rates by killing bacteria which contaminate the surface of the wound during operation."} {"id": "PMID:175070", "title": "Poland's syndrome.", "content": "Forty-three consecutive cases of Poland's syndrome were analyzed and the relevant literature was reviewed. The syndrome is not hereditary and is of unknown origin. It affects males more frequently than females. The clinical features are variable but always include congenital aplasia and syndactyly. The middle phalanges are hypoplastic or absent so that effectively there is only one interphalangeal joint. The syndactyly is usually incomplete and simple. It may involve all fingers and frequently includes the thumb, which then lies in the same plane as the fingers. Poland's syndrome may also include hypoplasia of the nipple and breast, hypoplasia of the upper ribs, herniation of the lung, contracture of the anterior axillary web, and elevated scapula. The arm and more frequently the forearm are hypoplastic. The right side is more often affected than the left. Surgical treatment by separating the syndactyly is recommended. In some cases a digit is removed to produce a three-fingered hand. Surgery is initiated by the age of one year and is completed by the time the child enters school, although periodic revisions may be necessary. Although the hand remains hypoplastic and functional capacity is limited by the inherent skeletal anomalies, surgical treatment improves functional capacity and cosmetic appearance in the majority of patients.", "contents": "Poland's syndrome. Forty-three consecutive cases of Poland's syndrome were analyzed and the relevant literature was reviewed. The syndrome is not hereditary and is of unknown origin. It affects males more frequently than females. The clinical features are variable but always include congenital aplasia and syndactyly. The middle phalanges are hypoplastic or absent so that effectively there is only one interphalangeal joint. The syndactyly is usually incomplete and simple. It may involve all fingers and frequently includes the thumb, which then lies in the same plane as the fingers. Poland's syndrome may also include hypoplasia of the nipple and breast, hypoplasia of the upper ribs, herniation of the lung, contracture of the anterior axillary web, and elevated scapula. The arm and more frequently the forearm are hypoplastic. The right side is more often affected than the left. Surgical treatment by separating the syndactyly is recommended. In some cases a digit is removed to produce a three-fingered hand. Surgery is initiated by the age of one year and is completed by the time the child enters school, although periodic revisions may be necessary. Although the hand remains hypoplastic and functional capacity is limited by the inherent skeletal anomalies, surgical treatment improves functional capacity and cosmetic appearance in the majority of patients."} {"id": "PMID:175071", "title": "Peripheral neuropathies associated with total hip arthroplasty.", "content": "The clinical and electromyographic findings in fourteen patients in whom peripheral nerve damage developed after total hip arthroplasty were reviewed (an incidence of 0.7 per cent in 2,012 procedures). In addition, a prospective study of the clinical, electromyographic, and nerve-conduction findings before and after arthroplasty was performed on twenty-eight patients who had thirty total hip arthroplasties. In the prospective study many patients showed evidence of mild nerve damage, most likely due to operative trauma. Peroneal neuropathies at the knee did not occur in either study. Nerve damage was more frequent in women, but no other predisposing factor could be identified. The prognosis for most patients with severe nerve injuries after total hip arthroplasty is good.", "contents": "Peripheral neuropathies associated with total hip arthroplasty. The clinical and electromyographic findings in fourteen patients in whom peripheral nerve damage developed after total hip arthroplasty were reviewed (an incidence of 0.7 per cent in 2,012 procedures). In addition, a prospective study of the clinical, electromyographic, and nerve-conduction findings before and after arthroplasty was performed on twenty-eight patients who had thirty total hip arthroplasties. In the prospective study many patients showed evidence of mild nerve damage, most likely due to operative trauma. Peroneal neuropathies at the knee did not occur in either study. Nerve damage was more frequent in women, but no other predisposing factor could be identified. The prognosis for most patients with severe nerve injuries after total hip arthroplasty is good."} {"id": "PMID:175072", "title": "The enhanced production of hyaluronic acid by cultured rat fibroblast cells treated with cyclic AMP and its dibutyryl derivative.", "content": "Cells of a newly established rat fibroblast line (SEN) in culture synthesize mucopolysaccharides, which have been identified as hyaluronic acid, chondroitin-4-sulfate and heparan sulfate. Treatment of the cells with adenosine 3':5'-cyclic monophosphate resulted in a marked stimulation of production of hyaluronic acid, but not of the other mucopolysaccharides. Treated cells also showed increased activity of hyaluronic acid synthetase, a reduction in growth rate, and morphological alteration. In addition, 5-bromodeoxyuridine was found to counteract greatly the cyclic AMP effect.", "contents": "The enhanced production of hyaluronic acid by cultured rat fibroblast cells treated with cyclic AMP and its dibutyryl derivative. Cells of a newly established rat fibroblast line (SEN) in culture synthesize mucopolysaccharides, which have been identified as hyaluronic acid, chondroitin-4-sulfate and heparan sulfate. Treatment of the cells with adenosine 3':5'-cyclic monophosphate resulted in a marked stimulation of production of hyaluronic acid, but not of the other mucopolysaccharides. Treated cells also showed increased activity of hyaluronic acid synthetase, a reduction in growth rate, and morphological alteration. In addition, 5-bromodeoxyuridine was found to counteract greatly the cyclic AMP effect."} {"id": "PMID:175073", "title": "Critical density for relaying in Dictyostelium discoideum and its relation to phosphodiesterase secretion into the extracellular medium.", "content": "The critical cell density for relaying in D. discoideum, N*, has been measured as a function of cell density, N, and time after harvesting, t. It has logarithmic dependence on N for 2.5 X 10(4)/cm2 less than N less than 7.5 X 10(5)/cm2 and saturates for N more than 1.0 X 10(6)/cm2. N* is an increasing function of time after harvesting. The phosphodiesterase (PDE) secretion rate on which N* depends is a constant. Expressions were derived which relate N* to PDE secretion and diffusion. They have been fitted to the data from time delay experiments yielding values of the PDE diffusion constant in 2% buffered agar, Dp + (2.25 +/- 0.15) X 10(-9) cm2/s, and the ratio of relaying threshold concentration to signal pulse size, C*/eta = (1.4 +/- 0.05) X 10(5) cm-3. N* has also been measured in the presence of various amounts of added beef heart PDE. The cAMP relaxation rates, I/tauo, due to beef heart PDE were calculated from the N* measurements and found to be proportional to amounts of added PDE for (I/tauo)max less than (10s-1). Finally, two kinds of inhibition have been observed in the PDE secretion. The PDE activity per cell is constant for N less than 8.0 X 10(4)/cm2, and decreases for larger N. It depends only on N for I/tau less than 10 s-1 and is strongly inhibited by extracellular PDE activity above this relaxation rate.", "contents": "Critical density for relaying in Dictyostelium discoideum and its relation to phosphodiesterase secretion into the extracellular medium. The critical cell density for relaying in D. discoideum, N*, has been measured as a function of cell density, N, and time after harvesting, t. It has logarithmic dependence on N for 2.5 X 10(4)/cm2 less than N less than 7.5 X 10(5)/cm2 and saturates for N more than 1.0 X 10(6)/cm2. N* is an increasing function of time after harvesting. The phosphodiesterase (PDE) secretion rate on which N* depends is a constant. Expressions were derived which relate N* to PDE secretion and diffusion. They have been fitted to the data from time delay experiments yielding values of the PDE diffusion constant in 2% buffered agar, Dp + (2.25 +/- 0.15) X 10(-9) cm2/s, and the ratio of relaying threshold concentration to signal pulse size, C*/eta = (1.4 +/- 0.05) X 10(5) cm-3. N* has also been measured in the presence of various amounts of added beef heart PDE. The cAMP relaxation rates, I/tauo, due to beef heart PDE were calculated from the N* measurements and found to be proportional to amounts of added PDE for (I/tauo)max less than (10s-1). Finally, two kinds of inhibition have been observed in the PDE secretion. The PDE activity per cell is constant for N less than 8.0 X 10(4)/cm2, and decreases for larger N. It depends only on N for I/tau less than 10 s-1 and is strongly inhibited by extracellular PDE activity above this relaxation rate."} {"id": "PMID:175074", "title": "Similarities of the Golgi apparatus membrane and the plasma membrane in rat liver cells.", "content": "A Golgi apparatus-rich fraction and a plasma membrane-rich fraction were isolated from a common homogenate of rat liver. Their respective buovant densities, appearances in the electron microscope and 5'-nucleotidase and UDP-galactose ovalbumin galactosyltransferase activities were in accord with published data on separately isolated Golgi apparatus-rich and plasma membrane-rich fractions. Contamination by endoplasmic reticulum and mitochondria was low. Gel electrophoresis of the membrane proteins of the Golgi apparatus-rich and plasma membrane-rich fractions (separately and mixed) showed a close similarity. After Neville's demonstration that electrophoretic patterns of membrane protein subunits from different subcellular fractions are easily distinguishable, the present work demonstrates an unusually close relationship between the Golgi apparatus membrane and the cell membrane. It is possible that membrane similarity may be mediated by the transfer of membrane-bound vesicles from the Golgi apparatus to the cell membrane.", "contents": "Similarities of the Golgi apparatus membrane and the plasma membrane in rat liver cells. A Golgi apparatus-rich fraction and a plasma membrane-rich fraction were isolated from a common homogenate of rat liver. Their respective buovant densities, appearances in the electron microscope and 5'-nucleotidase and UDP-galactose ovalbumin galactosyltransferase activities were in accord with published data on separately isolated Golgi apparatus-rich and plasma membrane-rich fractions. Contamination by endoplasmic reticulum and mitochondria was low. Gel electrophoresis of the membrane proteins of the Golgi apparatus-rich and plasma membrane-rich fractions (separately and mixed) showed a close similarity. After Neville's demonstration that electrophoretic patterns of membrane protein subunits from different subcellular fractions are easily distinguishable, the present work demonstrates an unusually close relationship between the Golgi apparatus membrane and the cell membrane. It is possible that membrane similarity may be mediated by the transfer of membrane-bound vesicles from the Golgi apparatus to the cell membrane."} {"id": "PMID:175075", "title": "The development of the relaying competence in Dictyostelium discoideum.", "content": "The fraction, X2, of a population of D. discoideum cells competent to relay an aggregative signal has been measured as a function of time, t, spent in interphase. X2(t) is less than 0.I up to 5 h, increases slowly to 0.4 by 8 h 20 min, and saturates at I by 10 h. The hypothesis that cellular interactions might enhance X2(t) was tested by mixing populations of cells set into interphase at different times. No interactions were found. External stimulation did not affect X2(t).", "contents": "The development of the relaying competence in Dictyostelium discoideum. The fraction, X2, of a population of D. discoideum cells competent to relay an aggregative signal has been measured as a function of time, t, spent in interphase. X2(t) is less than 0.I up to 5 h, increases slowly to 0.4 by 8 h 20 min, and saturates at I by 10 h. The hypothesis that cellular interactions might enhance X2(t) was tested by mixing populations of cells set into interphase at different times. No interactions were found. External stimulation did not affect X2(t)."} {"id": "PMID:175076", "title": "Extraction method and thin-layer chromatographic system for the determination of alpha-l-acetylmethadol and metabolites in biological fluids.", "content": "An extraction method and thin-layer chromatographic (TLC) system for the determination of alpha-l-acetylmethadol and its known metabolites (methadol, noracetylmethadol, dinoracetylmethadol, normethadol, 6-acetamide-4,4-diphenyl-3-heptanol, and N-methyl-6-acetamido-4,4-diphenyl-3-heptanol) are described. The parent drug and metabolites are extracted from biological fluids with ethyl acetate and separated by TLC using silica gel plates and a developing system of ethyl acetate-methanol-water-ammonia (85:10:1:1). This system may be used to quantitatively determine levels of radiolabeled drug and metabolites by scraping the TLC plates into 3-mm zonal fractions and measuring the amount of radioactivity by scintillation counting. A representative radiochromatogram obtained from an extract of monkey urine is shown.", "contents": "Extraction method and thin-layer chromatographic system for the determination of alpha-l-acetylmethadol and metabolites in biological fluids. An extraction method and thin-layer chromatographic (TLC) system for the determination of alpha-l-acetylmethadol and its known metabolites (methadol, noracetylmethadol, dinoracetylmethadol, normethadol, 6-acetamide-4,4-diphenyl-3-heptanol, and N-methyl-6-acetamido-4,4-diphenyl-3-heptanol) are described. The parent drug and metabolites are extracted from biological fluids with ethyl acetate and separated by TLC using silica gel plates and a developing system of ethyl acetate-methanol-water-ammonia (85:10:1:1). This system may be used to quantitatively determine levels of radiolabeled drug and metabolites by scraping the TLC plates into 3-mm zonal fractions and measuring the amount of radioactivity by scintillation counting. A representative radiochromatogram obtained from an extract of monkey urine is shown."} {"id": "PMID:175078", "title": "Partition high-pressure liquid-chromatographic systems for the separation of digitalis glycosides of the cardenolide group.", "content": "Several multi-component liquid-systems have been investigated on silica gel SI-60 supports of particle size 10 mum. By using two solvent systems, it was possible to separate 14 digitalis glycosides, ranging from genins of relatively low polarity to the highly polar deacetyl-lanatosides. Solvents with good ultraviolet transparency at 220 nm (lambdamax. for the butenolide ring) were chosen in order to improve the sensitivity of detection. The technique should also permit the determination of by-products and degradation products of these drug substances. Detection limits are as low as 15 ng for a 5 mul injection, and separation times vary between 4 and 20 min. The reproducibility of the retention times and the baseline separations attainable make the systems suitable for quantitative work.", "contents": "Partition high-pressure liquid-chromatographic systems for the separation of digitalis glycosides of the cardenolide group. Several multi-component liquid-systems have been investigated on silica gel SI-60 supports of particle size 10 mum. By using two solvent systems, it was possible to separate 14 digitalis glycosides, ranging from genins of relatively low polarity to the highly polar deacetyl-lanatosides. Solvents with good ultraviolet transparency at 220 nm (lambdamax. for the butenolide ring) were chosen in order to improve the sensitivity of detection. The technique should also permit the determination of by-products and degradation products of these drug substances. Detection limits are as low as 15 ng for a 5 mul injection, and separation times vary between 4 and 20 min. The reproducibility of the retention times and the baseline separations attainable make the systems suitable for quantitative work."} {"id": "PMID:175079", "title": "Studies on digitalis. IV. A method for thin-layer chromatographic separation and determination of digitoxin and cardioactive metabolites in human blood and urine.", "content": "A thin-layer chromatographic method for the separation of digitoxin and its cardioactive metabolites in one system is described. Pre-coated silica gel plates impregnated with 15% formamide solution in acetone were developed twice in the same direction (running distance 18cm) with ethyl methyl ketone-xylene (50:50) as solvent. The system showed no border-zone effects, and the reproducibility was good. Samples (5 ml) of serum or urine were extracted with dichloromethane, the extracts were evaporated, the residues were dissolved in 70% ethanol, the ethanol solutions were washed twice with light petroleum and then evaporated, and the residues were dissolved in chloroform-methanol for application to the thin-layer plates. After development, the metabolites were scraped from the plates and analyzed by means of a modified rubidium-86 method. The recovery for the whole procedure was 59%, and the sensitivity of the method permitted the determination of down to 0.5 ng per spot. The method will facilitate the study of digitoxin metabolism in patients undergoing treatment with the drug.", "contents": "Studies on digitalis. IV. A method for thin-layer chromatographic separation and determination of digitoxin and cardioactive metabolites in human blood and urine. A thin-layer chromatographic method for the separation of digitoxin and its cardioactive metabolites in one system is described. Pre-coated silica gel plates impregnated with 15% formamide solution in acetone were developed twice in the same direction (running distance 18cm) with ethyl methyl ketone-xylene (50:50) as solvent. The system showed no border-zone effects, and the reproducibility was good. Samples (5 ml) of serum or urine were extracted with dichloromethane, the extracts were evaporated, the residues were dissolved in 70% ethanol, the ethanol solutions were washed twice with light petroleum and then evaporated, and the residues were dissolved in chloroform-methanol for application to the thin-layer plates. After development, the metabolites were scraped from the plates and analyzed by means of a modified rubidium-86 method. The recovery for the whole procedure was 59%, and the sensitivity of the method permitted the determination of down to 0.5 ng per spot. The method will facilitate the study of digitoxin metabolism in patients undergoing treatment with the drug."} {"id": "PMID:175080", "title": "Thin-layer chromatography of homopyrimidazole derivatives.", "content": "The chromatographic behaviour of 14 homopyrimidazole derivatives has been studied on thin layers of silica gel, aluminium oxide and ammonia-saturated silica gel. The relationships between structure and chromatographic behaviour, as well as the most suitable systems for separating the individual derivatives, are discussed on the basis of RF values. The delta RMg values, showing the effect on the polarity, are given for certain functional groups.", "contents": "Thin-layer chromatography of homopyrimidazole derivatives. The chromatographic behaviour of 14 homopyrimidazole derivatives has been studied on thin layers of silica gel, aluminium oxide and ammonia-saturated silica gel. The relationships between structure and chromatographic behaviour, as well as the most suitable systems for separating the individual derivatives, are discussed on the basis of RF values. The delta RMg values, showing the effect on the polarity, are given for certain functional groups."} {"id": "PMID:175081", "title": "Fluorescence of tryptophan-containing peptides on paper or silica gel after treatment with formaldehyde, formaldehyde-ozone or formaldehyde-hydrochloric acid.", "content": "Sensitive and specific procedures for the chromatographic detection of tryptophan and tryptophan-containing peptides are described. Formaldehyde gas induces strong and characteristic fluorescence from tryptophan and peptides with NH2-terminal tryptophan residues on silica gel. On filter-paper, the detection of small amounts of these compounds requires the additional use of an oxidant, such as ozone. Treatment with formaldehyde-hydrochloric acid was used as a method for inducing fluorescence from tryptophan-containing peptides regardless of the position of the tryptophan residue in the peptide molecule. This reaction is useful for the chromatographic demonstration of small amounts of such peptides on both paper and silica gel. The spectral properties of the fluorophores of such tryptophan-containing peptides are distinctive and serve to distinguish them from all other known biogenic compounds that are capable of giving fluorescence with formaldehyde.", "contents": "Fluorescence of tryptophan-containing peptides on paper or silica gel after treatment with formaldehyde, formaldehyde-ozone or formaldehyde-hydrochloric acid. Sensitive and specific procedures for the chromatographic detection of tryptophan and tryptophan-containing peptides are described. Formaldehyde gas induces strong and characteristic fluorescence from tryptophan and peptides with NH2-terminal tryptophan residues on silica gel. On filter-paper, the detection of small amounts of these compounds requires the additional use of an oxidant, such as ozone. Treatment with formaldehyde-hydrochloric acid was used as a method for inducing fluorescence from tryptophan-containing peptides regardless of the position of the tryptophan residue in the peptide molecule. This reaction is useful for the chromatographic demonstration of small amounts of such peptides on both paper and silica gel. The spectral properties of the fluorophores of such tryptophan-containing peptides are distinctive and serve to distinguish them from all other known biogenic compounds that are capable of giving fluorescence with formaldehyde."} {"id": "PMID:175083", "title": "Prolonged corticotropic action of synthetic human ACTH in man.", "content": "The corticotropic activities of synthetic human ACTH (revised structure), synthetic porcine ACTH (unrevised structure) and synthetic 1-24ACTH were compared in 8 normal men by measuring the magnitude and duration of the elevation of plasma 11-hydroxy-corticosteroids following the injection of 1 mg of the peptides. The duration of response was significantly longer after human ACTH than following porcine or 1-24ACTH, although the initial responses were identical. This difference was noted after both intramuscular and intravenous administration. The data suggest that the carboxyterminal of the ACTH peptide is of some importance for biological activity and that biological species specificity may exist.", "contents": "Prolonged corticotropic action of synthetic human ACTH in man. The corticotropic activities of synthetic human ACTH (revised structure), synthetic porcine ACTH (unrevised structure) and synthetic 1-24ACTH were compared in 8 normal men by measuring the magnitude and duration of the elevation of plasma 11-hydroxy-corticosteroids following the injection of 1 mg of the peptides. The duration of response was significantly longer after human ACTH than following porcine or 1-24ACTH, although the initial responses were identical. This difference was noted after both intramuscular and intravenous administration. The data suggest that the carboxyterminal of the ACTH peptide is of some importance for biological activity and that biological species specificity may exist."} {"id": "PMID:175084", "title": "Size heterogeneity of beta-MSH in ectopic ACTH-producing tumors: presence of beta-LPH-like peptide.", "content": "Gel chromatographic, immunologic and biologic properties of beta-melanocyte-stimulating hormone (beta-MSH) in tumor tissues obtained from eight patients with the ectopic ACTH syndrome were studied and compared to those of pituitary beta-MSH. Size heterogeneity of immunoreactive beta-MSH was found in all the tumors studied as well as in normal human pituitaries. Both the tumors and pituitaries contained immunoreactive beta-MSH of a larger molecular size than the well-characterized beta-MSH of small molecular size. The large molecular weight beta-MSH also predominated in the plasma. It was found to be bioactive by an in vitro MSH assay, immunologically indistinguishable from human beta-MSH, and chromatographically very similar to beta-lipotropic hormone (beta-LPH). Tryptic digestion of the large molecular weight beta-MSH under controlled conditions promptly produced bioactive beta-MSH of small molecular size, followed by the appearance of immunologically active but biologically inert fragments. These results suggest that the ectopic ACTH-producing tumor as well as the pituitary elaborate beta-LPH-like peptide which might be the predominant component of immunoreactive beta-MSH in man.", "contents": "Size heterogeneity of beta-MSH in ectopic ACTH-producing tumors: presence of beta-LPH-like peptide. Gel chromatographic, immunologic and biologic properties of beta-melanocyte-stimulating hormone (beta-MSH) in tumor tissues obtained from eight patients with the ectopic ACTH syndrome were studied and compared to those of pituitary beta-MSH. Size heterogeneity of immunoreactive beta-MSH was found in all the tumors studied as well as in normal human pituitaries. Both the tumors and pituitaries contained immunoreactive beta-MSH of a larger molecular size than the well-characterized beta-MSH of small molecular size. The large molecular weight beta-MSH also predominated in the plasma. It was found to be bioactive by an in vitro MSH assay, immunologically indistinguishable from human beta-MSH, and chromatographically very similar to beta-lipotropic hormone (beta-LPH). Tryptic digestion of the large molecular weight beta-MSH under controlled conditions promptly produced bioactive beta-MSH of small molecular size, followed by the appearance of immunologically active but biologically inert fragments. These results suggest that the ectopic ACTH-producing tumor as well as the pituitary elaborate beta-LPH-like peptide which might be the predominant component of immunoreactive beta-MSH in man."} {"id": "PMID:175085", "title": "Corticotropic action of an intra-nasally applied synthetic ACTH derivative.", "content": "The corticotropic action of a synthetic ACTH derivative, D-Ser1 Lys17,18-1-18ACTH, after intranasal insufflation of 1 mg of the peptide was evaluated in 14 normal volunteers. Plasma cortisol and urinary 17-ketogenic steroids and 17-ketosteroids rose significantly over control values in all subjects (P less than 0.001). Plasma cortisol remained above the normal range for comparable clock times for 18 hr, but fell below 15 mug/100 ml after 12 hr. No evidence for suppression of the hypothalamo-pituitary axis was found the day after ACTH administration, as judged by normal plasma and urinary steroid values and normal diurnal variation. Intranasal administration of long-acting ACTH derivatives may provide a simple, painless and effective way to stimulate endogenous corticosteroid secretion.", "contents": "Corticotropic action of an intra-nasally applied synthetic ACTH derivative. The corticotropic action of a synthetic ACTH derivative, D-Ser1 Lys17,18-1-18ACTH, after intranasal insufflation of 1 mg of the peptide was evaluated in 14 normal volunteers. Plasma cortisol and urinary 17-ketogenic steroids and 17-ketosteroids rose significantly over control values in all subjects (P less than 0.001). Plasma cortisol remained above the normal range for comparable clock times for 18 hr, but fell below 15 mug/100 ml after 12 hr. No evidence for suppression of the hypothalamo-pituitary axis was found the day after ACTH administration, as judged by normal plasma and urinary steroid values and normal diurnal variation. Intranasal administration of long-acting ACTH derivatives may provide a simple, painless and effective way to stimulate endogenous corticosteroid secretion."} {"id": "PMID:175086", "title": "The effect of ACTH administration on serum estrogens, LH, and FSH in the aged.", "content": "The effect of administration of long acting ACTH on serum levels of estrogens, LH and FSH was studied in aged subjects. Nine women and 5 men between 66 and 90 years of age were examined. One milligram of long-acting synthetic ACTH was given in every 12 h for 2 days. Significant increases in serum estrone and estradiol levels were induced in parallel with serum cortisol at 24 hours and no further change was observed at 48 hours. The estrone/estradiol ratio increased from a control value of 3.0 to 4.0 at 24 hours and to 4.7 at 48 hours (P less than 0.02) compared to control values.", "contents": "The effect of ACTH administration on serum estrogens, LH, and FSH in the aged. The effect of administration of long acting ACTH on serum levels of estrogens, LH and FSH was studied in aged subjects. Nine women and 5 men between 66 and 90 years of age were examined. One milligram of long-acting synthetic ACTH was given in every 12 h for 2 days. Significant increases in serum estrone and estradiol levels were induced in parallel with serum cortisol at 24 hours and no further change was observed at 48 hours. The estrone/estradiol ratio increased from a control value of 3.0 to 4.0 at 24 hours and to 4.7 at 48 hours (P less than 0.02) compared to control values."} {"id": "PMID:175087", "title": "Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration.", "content": "Previous studies of the ability of the immature heart to respond to glucagon have yielded conflicting results. To test the possibility that the apparent discrepancies might be explained in part by species variability, isolated hearts of fetal mice and rats (13-22 days' gestational age) were studied under identical conditions in vitro. Changes in atrial rate and ventricular contractility were measured in spontaneously beating hearts exposed to glucagon, and activation of adenylate cyclase was assayed in cardiac homogenates. In mice of 16 days' gestational age or less, there was no change in heart rate in response to glucagon; at 17-18 days, minimal responsiveness was present; and after 19 days, 10muM glucagon caused an increase in spontaneous atrial rate of 30 +/- 4% (SEM) (P less than 0.001). Measurement of the extent and speed of volume displacement of the isotonically contracting hearts with a specially constructed capacitance transducer revealed that ventricular inotropic responsiveness also appeared after 17-19 days. Cardiac stores of glycogen were reduced in older hearts exposed to glucagon, but not in those aged less than 16 days. In contrast, glucagon failed to activate adenylate cyclase in homogenates of hearts of fetal mice at any age. Furthermore, glucagon failed to elicit an increase in the concentration of cyclic AMP in spontaneously beating hearts that developed tachycardia. Responses in hearts of fetal rats were distinctly different from those in mouse hearts: at no age was there any change in heart rate, strength of contraction, glycogen content, or adenylate cyclase activation. Thus, there are major species differences in cardiac pharmacological maturation. Although the mouse heart develops the ability to increase its rate and strength of contraction and to undergo glycogenolysis in response to glucagon well before birth, the rat heart does not. In addition, there is an apparent disparity in late fetal mouse hearts between the ability of glucagon to induce functional responses and its ability to stimulate adenylate cyclase and increase cyclic AMP levels. It is impossible, of course, to rule out absolutely the possibility that localized increases in a critical cyclic AMP pool were present but too small to measure in the entire tissue. Nevertheless, the most obvious interpretation of our results is that they are compatible with the hypothesis that glucagon may exert some of its hemodynamic effects independently from the adenylate cyclase-cyclic AMP system in the late-fetal mouse heart.", "contents": "Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration. Previous studies of the ability of the immature heart to respond to glucagon have yielded conflicting results. To test the possibility that the apparent discrepancies might be explained in part by species variability, isolated hearts of fetal mice and rats (13-22 days' gestational age) were studied under identical conditions in vitro. Changes in atrial rate and ventricular contractility were measured in spontaneously beating hearts exposed to glucagon, and activation of adenylate cyclase was assayed in cardiac homogenates. In mice of 16 days' gestational age or less, there was no change in heart rate in response to glucagon; at 17-18 days, minimal responsiveness was present; and after 19 days, 10muM glucagon caused an increase in spontaneous atrial rate of 30 +/- 4% (SEM) (P less than 0.001). Measurement of the extent and speed of volume displacement of the isotonically contracting hearts with a specially constructed capacitance transducer revealed that ventricular inotropic responsiveness also appeared after 17-19 days. Cardiac stores of glycogen were reduced in older hearts exposed to glucagon, but not in those aged less than 16 days. In contrast, glucagon failed to activate adenylate cyclase in homogenates of hearts of fetal mice at any age. Furthermore, glucagon failed to elicit an increase in the concentration of cyclic AMP in spontaneously beating hearts that developed tachycardia. Responses in hearts of fetal rats were distinctly different from those in mouse hearts: at no age was there any change in heart rate, strength of contraction, glycogen content, or adenylate cyclase activation. Thus, there are major species differences in cardiac pharmacological maturation. Although the mouse heart develops the ability to increase its rate and strength of contraction and to undergo glycogenolysis in response to glucagon well before birth, the rat heart does not. In addition, there is an apparent disparity in late fetal mouse hearts between the ability of glucagon to induce functional responses and its ability to stimulate adenylate cyclase and increase cyclic AMP levels. It is impossible, of course, to rule out absolutely the possibility that localized increases in a critical cyclic AMP pool were present but too small to measure in the entire tissue. Nevertheless, the most obvious interpretation of our results is that they are compatible with the hypothesis that glucagon may exert some of its hemodynamic effects independently from the adenylate cyclase-cyclic AMP system in the late-fetal mouse heart."} {"id": "PMID:175088", "title": "Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.", "content": "This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme.", "contents": "Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion. This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme."} {"id": "PMID:175089", "title": "The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.", "content": "Data from cultured cells have suggested that cyclic AMP and cyclic GMP may be important determinants of cell growth and transformation. However, few studies have examined cyclic nucleotide content and metabolism in naturally occurring tumors of man. Accordingly, in the present study we compared cAMP and cGMP levels and metabolism in carcinomas of the human colon to those of the adjacent uninvolved mucosa after therapeutic resection of these tissues. The cAMP content of the tumors, determined in samples frozen 30 min after excision, was significantly lower than that of the adjacent mucosa, when expressed on the basis of tissue wet weight, protein, or DNA content. By contrast, the cGMP content of the tumors was higher than that of the surrounding mucosa if calculated on the basis of tissue wet weight, but this difference did not persist when correction was made for the higher protein or DNA content of the tumors. Incubation of slices of mucosa or tumor with or without theophylline in vitro increased tissue cAMP and cGMP content above levels observed in frozen samples of the same tissue. However, after such incubations cAMP levels in the tumors remained clearly below that of the mucosa, while cGMP content of the two tissues did not differ. The failure of theophylline to abolish differences in cAMP content and the comparable activities of high and low Km cAMP-phosphodiesterase in homogenates of the two tissues suggested that the lower cAMP content of the tumors was a consequence of diminished cAMP synthesis rather than enhanced degradation. This possibility was supported by the reduction in basal and maximal prostaglandin E1 (PGE1)-responsive adenylate cyclase activity found in tumor homogenates relative to those of mucosa, and the lower levels of cAMP in tumor slices after incubation of the tissues with a maximal dose of PGE1 and theophylline. Since NaF-responsive adenylate cyclase activity was not significantly reduced in the tumors, the lower basal and PGE1 activities may not be related to a deficiency of the catalytic unit of the cyclase complex in this tissue. The role of reduced activity of the adenylate cyclase-cAMP system and/or reduced tissue cAMP-to-cGMP ratios in the pathogenesis of colonic carcinoma is uncertain, but these changes might favor unregulated cellular proliferation.", "contents": "The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon. Data from cultured cells have suggested that cyclic AMP and cyclic GMP may be important determinants of cell growth and transformation. However, few studies have examined cyclic nucleotide content and metabolism in naturally occurring tumors of man. Accordingly, in the present study we compared cAMP and cGMP levels and metabolism in carcinomas of the human colon to those of the adjacent uninvolved mucosa after therapeutic resection of these tissues. The cAMP content of the tumors, determined in samples frozen 30 min after excision, was significantly lower than that of the adjacent mucosa, when expressed on the basis of tissue wet weight, protein, or DNA content. By contrast, the cGMP content of the tumors was higher than that of the surrounding mucosa if calculated on the basis of tissue wet weight, but this difference did not persist when correction was made for the higher protein or DNA content of the tumors. Incubation of slices of mucosa or tumor with or without theophylline in vitro increased tissue cAMP and cGMP content above levels observed in frozen samples of the same tissue. However, after such incubations cAMP levels in the tumors remained clearly below that of the mucosa, while cGMP content of the two tissues did not differ. The failure of theophylline to abolish differences in cAMP content and the comparable activities of high and low Km cAMP-phosphodiesterase in homogenates of the two tissues suggested that the lower cAMP content of the tumors was a consequence of diminished cAMP synthesis rather than enhanced degradation. This possibility was supported by the reduction in basal and maximal prostaglandin E1 (PGE1)-responsive adenylate cyclase activity found in tumor homogenates relative to those of mucosa, and the lower levels of cAMP in tumor slices after incubation of the tissues with a maximal dose of PGE1 and theophylline. Since NaF-responsive adenylate cyclase activity was not significantly reduced in the tumors, the lower basal and PGE1 activities may not be related to a deficiency of the catalytic unit of the cyclase complex in this tissue. The role of reduced activity of the adenylate cyclase-cAMP system and/or reduced tissue cAMP-to-cGMP ratios in the pathogenesis of colonic carcinoma is uncertain, but these changes might favor unregulated cellular proliferation."} {"id": "PMID:175090", "title": "Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets.", "content": "Since many cell types have been shown to respond to extracellular stimulation with a rapid increase in phosphatidylinositol turnover, the present studies were undertaken to determine whether carbohydrate-stimulated insulin secretion from the isolated rat pancreatic islet is accompanied by detectable alterations in the phosphatidylinositol metabolism of this tissue. We have demonstrated that rat pancreatic islets incubated with tritiated myo-inositol rapidly incorporate radioactivity into islet phosphatidylinositol. Incubation of prelabeled islets with elevated concentrations of carbohydrates which stimulate insulin secretion (D-glucose and D-mannose) results in a decrease in the recovery of lipid-bound radioactivity, whereas incubation with carbohydrates which do not stimulate insulin secretion (D-galactose and myo-inositol) has no effect upon the recovery of lipid-bound radioactivity. Within 2 min of exposure of prelabeled islets to elevated concentrations of D-glucose, a decrease in the recovery of [2-3H]myo-inositol-derived radioactivity in islet phosphatidylinositol can be demonstrated. When islets prelabeled with [2-3H]myo-inositol are perifused with elevated concentrations of D-glucose or D-mannose (but not D-galactose or myoinositol) a rapid and transient increase in the rate of extracellular release of water-soluble radioactivity is observed. Since a significant fraction of the radioactivity released under these conditions is in the form of myo-inositol phosphate, cyclic myo-inositol-1,2-phosphate, and glycerophosphorylmyo-inositol, it is presumably derived from the cleavage of labeled islet phosphatidylinositol. It is speculated that alterations in the metabolism of myo-inositol-containing phospholipids may have a functional role in the process of insulin secretion from the pancreatic beta cell.", "contents": "Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets. Since many cell types have been shown to respond to extracellular stimulation with a rapid increase in phosphatidylinositol turnover, the present studies were undertaken to determine whether carbohydrate-stimulated insulin secretion from the isolated rat pancreatic islet is accompanied by detectable alterations in the phosphatidylinositol metabolism of this tissue. We have demonstrated that rat pancreatic islets incubated with tritiated myo-inositol rapidly incorporate radioactivity into islet phosphatidylinositol. Incubation of prelabeled islets with elevated concentrations of carbohydrates which stimulate insulin secretion (D-glucose and D-mannose) results in a decrease in the recovery of lipid-bound radioactivity, whereas incubation with carbohydrates which do not stimulate insulin secretion (D-galactose and myo-inositol) has no effect upon the recovery of lipid-bound radioactivity. Within 2 min of exposure of prelabeled islets to elevated concentrations of D-glucose, a decrease in the recovery of [2-3H]myo-inositol-derived radioactivity in islet phosphatidylinositol can be demonstrated. When islets prelabeled with [2-3H]myo-inositol are perifused with elevated concentrations of D-glucose or D-mannose (but not D-galactose or myoinositol) a rapid and transient increase in the rate of extracellular release of water-soluble radioactivity is observed. Since a significant fraction of the radioactivity released under these conditions is in the form of myo-inositol phosphate, cyclic myo-inositol-1,2-phosphate, and glycerophosphorylmyo-inositol, it is presumably derived from the cleavage of labeled islet phosphatidylinositol. It is speculated that alterations in the metabolism of myo-inositol-containing phospholipids may have a functional role in the process of insulin secretion from the pancreatic beta cell."} {"id": "PMID:175091", "title": "Extraosseous calcification. Evidence for abnormal pyrophosphate metabolism in uremia.", "content": "The inorganic constituents and crystalline features of extraosseous calcium-phosphate deposits obtained from dialyzed uremic and hypercalcemic patients were studied. Visceral calcification (heart, lung, and kidney) in hypercalcemic patients exhibited either an amorphous or apatitic X-ray diffraction pattern. Uremic visceral calcification consistently gave an amorphous diffraction pattern. Although the calcium content of uremic and hypercalcemic visceral deposits was similar, other inorganic constituents were different. The mean pyrophosphate was 11 +/- 11.8 and magnesium 4.91 +/- 3.86 mg/g in the uremic group as compared to 0.92 +/- 0.24 and 1.36 +/- 1.26 mg/g in the hypercalcemic group (P less than 0.025). After incineration hypercalcemic visceral deposits having an amorphous diffraction pattern were found to generate pyrophosphate supporting the presence of brushite in these deposits. The small amount of pyrophosphate in apatitic deposits from both uremic and hypercalcemic patients actually decreased after incineration and the pyrophosphate content of uremic visceral deposits was unchanged by incineration. It is concluded that in hypercalcemic patients the initial visceral deposit is brushite which is subsequently transformed to apatite. Arterial and tumoral calcium-phosphate deposits in uremic patients were also apatite. Uremic visceral calcium-phosphate deposits are an unique mineral high in magnesium with approximately 30% of the phosphorus present as pyrophosphate. The high pyrophosphate content of these deposits could alter their crystalline structure and prevent the transformation to apatite. The infrared features, high magnesium content of the deposit, and resistance of pyrophosphate in the deposit to hydrolysis by pyrophosphatase suggests that the pyrophosphate may be deposited as the magnesium salt.", "contents": "Extraosseous calcification. Evidence for abnormal pyrophosphate metabolism in uremia. The inorganic constituents and crystalline features of extraosseous calcium-phosphate deposits obtained from dialyzed uremic and hypercalcemic patients were studied. Visceral calcification (heart, lung, and kidney) in hypercalcemic patients exhibited either an amorphous or apatitic X-ray diffraction pattern. Uremic visceral calcification consistently gave an amorphous diffraction pattern. Although the calcium content of uremic and hypercalcemic visceral deposits was similar, other inorganic constituents were different. The mean pyrophosphate was 11 +/- 11.8 and magnesium 4.91 +/- 3.86 mg/g in the uremic group as compared to 0.92 +/- 0.24 and 1.36 +/- 1.26 mg/g in the hypercalcemic group (P less than 0.025). After incineration hypercalcemic visceral deposits having an amorphous diffraction pattern were found to generate pyrophosphate supporting the presence of brushite in these deposits. The small amount of pyrophosphate in apatitic deposits from both uremic and hypercalcemic patients actually decreased after incineration and the pyrophosphate content of uremic visceral deposits was unchanged by incineration. It is concluded that in hypercalcemic patients the initial visceral deposit is brushite which is subsequently transformed to apatite. Arterial and tumoral calcium-phosphate deposits in uremic patients were also apatite. Uremic visceral calcium-phosphate deposits are an unique mineral high in magnesium with approximately 30% of the phosphorus present as pyrophosphate. The high pyrophosphate content of these deposits could alter their crystalline structure and prevent the transformation to apatite. The infrared features, high magnesium content of the deposit, and resistance of pyrophosphate in the deposit to hydrolysis by pyrophosphatase suggests that the pyrophosphate may be deposited as the magnesium salt."} {"id": "PMID:175092", "title": "Bone pyrophosphate in uremia and its association with extraosseous calcification.", "content": "The mean bone pyrophosphate was 0.360 +/- 0.15 mg/g in 8 controls and 1.22 +/- 1.39 mg/g bone in 27 uremic patients (P less than 0.0025). 13 of the 27 uremic patients had bone pyrophosphate levels greater than 2 SD above control values. The ash content of uremic bones with increased pyrophosphate levels (group II) was 56 +/- 9% as compared to 64 +/- 2% in control bones (P less than 0.01) and 60 +/- 7% in uremic bones having normal pyrophosphate levels (P less than 0.1) (group I). The magnesium content of bones in group II was 338 +/- 47 as compared to 211 +/- 13 (P less than 0.0005) in the controls and 294 +/- 73 mmol/kg ash (P less than 0.05) in group I. In group II, but not group I, there was a significant inverse correlation between duration of dialysis and percent bone ash (r = -0.59) (P less than 0.05). A definite relationship existed between elevated bone pyrophosphate levels and soft tissue calcification. In group II the mean pulmonary calcium content was 530 +/- 459 as compared to 32 +/- 26 mmol/kg/ash in group I (P less than 0.0025). All patients with a bone pyrophosphate level greater than 1.4 mg/g bone had extensive pulmonary calcification. It is concluded that the excess bone pyrophosphate present in some uremic patients is either deposited in the apatite crystal in the transphosphorylated form or else as the magnesium salt since the pyrophosphate is resistant to pyrophosphatase and surface adsorption of pyrophosphate is not altered by the increased bone pyrophosphate levels. The excess bone pyrophosphate could disturb bone calcification mechanisms in uremic patients. The association between increased bone pyrophosphate and soft tissue calcification suggests that the disordered pyrophosphate metabolism may be important in the pathogenesis of extraosseous calcification.", "contents": "Bone pyrophosphate in uremia and its association with extraosseous calcification. The mean bone pyrophosphate was 0.360 +/- 0.15 mg/g in 8 controls and 1.22 +/- 1.39 mg/g bone in 27 uremic patients (P less than 0.0025). 13 of the 27 uremic patients had bone pyrophosphate levels greater than 2 SD above control values. The ash content of uremic bones with increased pyrophosphate levels (group II) was 56 +/- 9% as compared to 64 +/- 2% in control bones (P less than 0.01) and 60 +/- 7% in uremic bones having normal pyrophosphate levels (P less than 0.1) (group I). The magnesium content of bones in group II was 338 +/- 47 as compared to 211 +/- 13 (P less than 0.0005) in the controls and 294 +/- 73 mmol/kg ash (P less than 0.05) in group I. In group II, but not group I, there was a significant inverse correlation between duration of dialysis and percent bone ash (r = -0.59) (P less than 0.05). A definite relationship existed between elevated bone pyrophosphate levels and soft tissue calcification. In group II the mean pulmonary calcium content was 530 +/- 459 as compared to 32 +/- 26 mmol/kg/ash in group I (P less than 0.0025). All patients with a bone pyrophosphate level greater than 1.4 mg/g bone had extensive pulmonary calcification. It is concluded that the excess bone pyrophosphate present in some uremic patients is either deposited in the apatite crystal in the transphosphorylated form or else as the magnesium salt since the pyrophosphate is resistant to pyrophosphatase and surface adsorption of pyrophosphate is not altered by the increased bone pyrophosphate levels. The excess bone pyrophosphate could disturb bone calcification mechanisms in uremic patients. The association between increased bone pyrophosphate and soft tissue calcification suggests that the disordered pyrophosphate metabolism may be important in the pathogenesis of extraosseous calcification."} {"id": "PMID:175093", "title": "Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes.", "content": "The lipoproteins of rats fed a high sucrose diet and made diabetic by administration of 45 mg/kg of streptozotocin were studied. All lipoprotein classes were found to be present in increased concentrations. The apolipoprotein composition of the various lipoprotein fractions was studied by polyacrylamide-gel electrophoresis in the presence of 8 M urea, isoelectric focusing in the presence of 8 M urea, and sodium dodecyl sulfate gel electrophoresis in polyacrylamide gels. In the very low density lipoproteins (VLDL) of diabetic rats, there was a marked alteration in the relative amounts of C proteins by polyacrylamide-gel electrophoresis, and this was found by isoelectric focusing to be primarily a relative increase in C-III-3 apoprotein and a decrease in C-III-O. In addition, in the diabetic rats, the VLDL contained a protein of mol wt 46,000, the A-IV protein, which normally is only present in the high density lipoproteins. In the high density lipoproteins, (HDL) the same alterations in pattern of the C proteins seen in the VLDL were present. Furthermore, the arginine-rich and A-IV protein normally present in HDL could not be detected in the HDL, although the other apolipoproteins are present. Apolipoprotein concentrations were determined by quantitative immunoelectrophoresis. It was found that in the diabetic rats there was an increase in the total amount of apo-B in the plasma, with the increment divided proportionately between the VLDL and the low density lipoprotein (LDL). The total apo-C concentration of plasma increased minimally. The A-IV concentration of plasma increased by 27%; it decreased markedly in the HDL, but appeared in increased amounts in both VLDL and in the d greater than 1.21 fraction. The arginine-rich protein decreased by 63% in the plasma and decreased significantly in the HDL, but increased in VLDL, LDL, and in the d greater than 1.21 fraction. These alterations in apolipoprotein patterns in diabetic animals suggest that the apolipoproteins may play an important role in determining the concentration of various lipoprotein fractions, or may be the result of altered metabolism of the lipoproteins. These lipoproteins with altered apolipoprotein composition may have important biologic differences from normal lipoporteins. Nevertheless, the HDL, despite the fact that it is deficient in some of its major constituents, was unchanged in its cholesterol content.", "contents": "Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes. The lipoproteins of rats fed a high sucrose diet and made diabetic by administration of 45 mg/kg of streptozotocin were studied. All lipoprotein classes were found to be present in increased concentrations. The apolipoprotein composition of the various lipoprotein fractions was studied by polyacrylamide-gel electrophoresis in the presence of 8 M urea, isoelectric focusing in the presence of 8 M urea, and sodium dodecyl sulfate gel electrophoresis in polyacrylamide gels. In the very low density lipoproteins (VLDL) of diabetic rats, there was a marked alteration in the relative amounts of C proteins by polyacrylamide-gel electrophoresis, and this was found by isoelectric focusing to be primarily a relative increase in C-III-3 apoprotein and a decrease in C-III-O. In addition, in the diabetic rats, the VLDL contained a protein of mol wt 46,000, the A-IV protein, which normally is only present in the high density lipoproteins. In the high density lipoproteins, (HDL) the same alterations in pattern of the C proteins seen in the VLDL were present. Furthermore, the arginine-rich and A-IV protein normally present in HDL could not be detected in the HDL, although the other apolipoproteins are present. Apolipoprotein concentrations were determined by quantitative immunoelectrophoresis. It was found that in the diabetic rats there was an increase in the total amount of apo-B in the plasma, with the increment divided proportionately between the VLDL and the low density lipoprotein (LDL). The total apo-C concentration of plasma increased minimally. The A-IV concentration of plasma increased by 27%; it decreased markedly in the HDL, but appeared in increased amounts in both VLDL and in the d greater than 1.21 fraction. The arginine-rich protein decreased by 63% in the plasma and decreased significantly in the HDL, but increased in VLDL, LDL, and in the d greater than 1.21 fraction. These alterations in apolipoprotein patterns in diabetic animals suggest that the apolipoproteins may play an important role in determining the concentration of various lipoprotein fractions, or may be the result of altered metabolism of the lipoproteins. These lipoproteins with altered apolipoprotein composition may have important biologic differences from normal lipoporteins. Nevertheless, the HDL, despite the fact that it is deficient in some of its major constituents, was unchanged in its cholesterol content."} {"id": "PMID:175094", "title": "Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A \"short-loop\" regulatory mechanism?", "content": "We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a \"short-loop\" negative feedback regulating thyroid function.", "contents": "Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A \"short-loop\" regulatory mechanism? We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a \"short-loop\" negative feedback regulating thyroid function."} {"id": "PMID:175095", "title": "Ultrasound of the parotid gland.", "content": "Five cases of parotid gland masses were studied by ultrasound. Only retention cysts and true cysts of the parotid gland appear sonolucent at low and high gain settings. Benign and malignant tumor present as solid masses except for the Warthin's tumor which is sonolucent at lower gain settings but has a lattice of internal echoes at higher gain settings.", "contents": "Ultrasound of the parotid gland. Five cases of parotid gland masses were studied by ultrasound. Only retention cysts and true cysts of the parotid gland appear sonolucent at low and high gain settings. Benign and malignant tumor present as solid masses except for the Warthin's tumor which is sonolucent at lower gain settings but has a lattice of internal echoes at higher gain settings."} {"id": "PMID:175096", "title": "False positive infectious mononucleosis serology in epilepsy.", "content": "Positive serum tests for infectious mononucleosis (IM) unaccompanied by the clinical syndrome or blood changes characteristic of the disease were detected in 39/177 (22%) mentally subnormal patients investigated with three different commercially available IM slide tests. Slide positively was still detectable six months later in 27/35 (77%) positive reactors. Positive IM slide tests were significantly associated with anticonvulsant, primarily phenobarbitone therapy and with concomitant elevations of immunoglobulins IgG and IgM. Epstein Barr virus antibodies were not detectable in the sera of 8/38 (21%) positive slide reactors. The implications of these observations are discussed and attention is drawn to the variations in sensitivity, specificity, and comparability of different IM slide tests.", "contents": "False positive infectious mononucleosis serology in epilepsy. Positive serum tests for infectious mononucleosis (IM) unaccompanied by the clinical syndrome or blood changes characteristic of the disease were detected in 39/177 (22%) mentally subnormal patients investigated with three different commercially available IM slide tests. Slide positively was still detectable six months later in 27/35 (77%) positive reactors. Positive IM slide tests were significantly associated with anticonvulsant, primarily phenobarbitone therapy and with concomitant elevations of immunoglobulins IgG and IgM. Epstein Barr virus antibodies were not detectable in the sera of 8/38 (21%) positive slide reactors. The implications of these observations are discussed and attention is drawn to the variations in sensitivity, specificity, and comparability of different IM slide tests."} {"id": "PMID:175097", "title": "Multifocal malignant histiocytoma.", "content": "The pathology of malignant histiocytoma has recently been defined and its malignancy confirmed beyond doubt. A unique example of this tumour is described, a search of the literature having failed to find a previously recorded case with a multifocal origin.", "contents": "Multifocal malignant histiocytoma. The pathology of malignant histiocytoma has recently been defined and its malignancy confirmed beyond doubt. A unique example of this tumour is described, a search of the literature having failed to find a previously recorded case with a multifocal origin."} {"id": "PMID:175098", "title": "EB virus antibody and infectious mononucleosis in a boarding school for boys.", "content": "A study of EB virus antibody was undertaken in a boarding school for boys between 11 and 18 years of age; 35% of boys had EBV antibody when first sampled and a small number acquired antibody each year. Some of these boys had had no recorded illness during the period before the first positive sample and some developed classic infectious mononucleosis which was accompainied by a positive heterophil antibody test and detection of EB virus specific IgM. In a school of 800 boys there were 13 cases of infectious mononucleosis in four years.", "contents": "EB virus antibody and infectious mononucleosis in a boarding school for boys. A study of EB virus antibody was undertaken in a boarding school for boys between 11 and 18 years of age; 35% of boys had EBV antibody when first sampled and a small number acquired antibody each year. Some of these boys had had no recorded illness during the period before the first positive sample and some developed classic infectious mononucleosis which was accompainied by a positive heterophil antibody test and detection of EB virus specific IgM. In a school of 800 boys there were 13 cases of infectious mononucleosis in four years."} {"id": "PMID:175099", "title": "An epidemic of diarrhoea in human neonates involving a reovirus-like agent and 'enteropathogenic' serotypes of Escherichia coli.", "content": "During December 1974, an epidemic of diarrhoea occurred in the Royal Children's Hospital, Melbourne, in a ward caring for neonates with acute or chronic medical and surgical problems. Electron microscopy of diarrhoeal faeces revealed a reovirus-like particle ('duovirus' or 'rotavirus') known to cause acute enteritis in older children. This virus is considered to have been primarily involved in the aetiology of the epidemic. In addition, three 'enteropathogenic' serotypes of Escherichia coli were isolated from babies during the epidemic, but none produced enterotoxin when tested in ligated ileal loops of rabbits or in monolayers of Y1 adrenal cells. Further epidemics of neonatal diarrhoea must be studied using culture and electron microscopy of faeces to determine the relative importance of this virus and of E. coli in the aetiology of diarrhoea in this age-group.", "contents": "An epidemic of diarrhoea in human neonates involving a reovirus-like agent and 'enteropathogenic' serotypes of Escherichia coli. During December 1974, an epidemic of diarrhoea occurred in the Royal Children's Hospital, Melbourne, in a ward caring for neonates with acute or chronic medical and surgical problems. Electron microscopy of diarrhoeal faeces revealed a reovirus-like particle ('duovirus' or 'rotavirus') known to cause acute enteritis in older children. This virus is considered to have been primarily involved in the aetiology of the epidemic. In addition, three 'enteropathogenic' serotypes of Escherichia coli were isolated from babies during the epidemic, but none produced enterotoxin when tested in ligated ileal loops of rabbits or in monolayers of Y1 adrenal cells. Further epidemics of neonatal diarrhoea must be studied using culture and electron microscopy of faeces to determine the relative importance of this virus and of E. coli in the aetiology of diarrhoea in this age-group."} {"id": "PMID:175100", "title": "Urinary cyclic adenosine monophosphate in young adults and elderly subjects.", "content": "The 24-hour urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMP) was measured by a protein-binding assay in 55 healthy volunteers (aged 20-35 yr) and in 30 hospitalized elderly subjects (aged 70-93 yr). In the older subjects the mean 24-hour cAMP excretion was significantly lower; the correlation between cAMP excretion and age demonstrated a progressive decrease from the age of 70 to the tenth decade. Many different factors could account for the reduced urinary cAMP excretion in elderly subjects: a decline in the reactivity of the adenyl cyclase-cAMP system related to physiological ageing; reduced physical activity; a reduction in the glomerular filtration rate or decreased production of cAMP by tubular cells in the senile kidney.", "contents": "Urinary cyclic adenosine monophosphate in young adults and elderly subjects. The 24-hour urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMP) was measured by a protein-binding assay in 55 healthy volunteers (aged 20-35 yr) and in 30 hospitalized elderly subjects (aged 70-93 yr). In the older subjects the mean 24-hour cAMP excretion was significantly lower; the correlation between cAMP excretion and age demonstrated a progressive decrease from the age of 70 to the tenth decade. Many different factors could account for the reduced urinary cAMP excretion in elderly subjects: a decline in the reactivity of the adenyl cyclase-cAMP system related to physiological ageing; reduced physical activity; a reduction in the glomerular filtration rate or decreased production of cAMP by tubular cells in the senile kidney."} {"id": "PMID:175101", "title": "Tumor- and drug-induced cutaneous neuro-phospholipidosis.", "content": "Drugs and metastatic malignant tumors induce severe alterations in cutaneous axons. The most prominent ultrastructural feature of axonal dystrophy of this type was the presence of multiple lamellated osmiophilic bodies (LOB), similar to those occurring in hereditary disorders with increase of brain gangliosides and lipid storage. Chloroquine, ergotamine, ethaverine and chronic abuse of non-narcotic analgesic drugs seem to be responsible for the drug-induced cutaneous neuro-phospholipidosis, whereas the same condition was found in two patients with metastatic bronchogenic carcinoma and malignant melanoma.", "contents": "Tumor- and drug-induced cutaneous neuro-phospholipidosis. Drugs and metastatic malignant tumors induce severe alterations in cutaneous axons. The most prominent ultrastructural feature of axonal dystrophy of this type was the presence of multiple lamellated osmiophilic bodies (LOB), similar to those occurring in hereditary disorders with increase of brain gangliosides and lipid storage. Chloroquine, ergotamine, ethaverine and chronic abuse of non-narcotic analgesic drugs seem to be responsible for the drug-induced cutaneous neuro-phospholipidosis, whereas the same condition was found in two patients with metastatic bronchogenic carcinoma and malignant melanoma."} {"id": "PMID:175102", "title": "Immunological properties of bovine serum lipoproteins and chemical analysis of their protein moieties.", "content": "Four classes of bovine serum lipoproteins were isolated by precipitation with dextran sulfate, ultracentrifugation, and preparative electrophoresis on polyacrylamide gel. Very low density lipoprotein (d less than 1.019 g/ml) was related immunologically to low density lipoprotein-two (d 1.039 to 1.060 g/ml) and high density lipoprotein (d 1.060 to 1.210 g/ml) was related immunologically to low density lipoprotein-one (d 1.019 to 1.039 g/ml), but the two pairs were immunologically distinct. The major N-terminal amino acid of both high density lipoprotein and low density lipoprotein-one was aspartic acid, and that of low density lipoprotein-two was glutamic acid. Very low density lipoprotein had both aspartic acid and glutamic acid as the major N-terminal amino acids. None of the lipoproteins was identical with any other with respect to amino acid composition, but high density lipoprotein and low density lipoprotein-one were similar to each other and different from low density lipoprotein-two. Very low density lipoprotein was similar to both low density lipoprotein-one and low density lipoprotein-two. It is concluded that the proteins of high density lipoprotein and of low density lipoprotein-one are related and are different from that of low density lipoprotein-two. The protein of very low density lipoprotein is related to that of low density lipoprotein-two but may contain polypeptides of high density lipoprotein or low density lipoprotein-one.", "contents": "Immunological properties of bovine serum lipoproteins and chemical analysis of their protein moieties. Four classes of bovine serum lipoproteins were isolated by precipitation with dextran sulfate, ultracentrifugation, and preparative electrophoresis on polyacrylamide gel. Very low density lipoprotein (d less than 1.019 g/ml) was related immunologically to low density lipoprotein-two (d 1.039 to 1.060 g/ml) and high density lipoprotein (d 1.060 to 1.210 g/ml) was related immunologically to low density lipoprotein-one (d 1.019 to 1.039 g/ml), but the two pairs were immunologically distinct. The major N-terminal amino acid of both high density lipoprotein and low density lipoprotein-one was aspartic acid, and that of low density lipoprotein-two was glutamic acid. Very low density lipoprotein had both aspartic acid and glutamic acid as the major N-terminal amino acids. None of the lipoproteins was identical with any other with respect to amino acid composition, but high density lipoprotein and low density lipoprotein-one were similar to each other and different from low density lipoprotein-two. Very low density lipoprotein was similar to both low density lipoprotein-one and low density lipoprotein-two. It is concluded that the proteins of high density lipoprotein and of low density lipoprotein-one are related and are different from that of low density lipoprotein-two. The protein of very low density lipoprotein is related to that of low density lipoprotein-two but may contain polypeptides of high density lipoprotein or low density lipoprotein-one."} {"id": "PMID:175103", "title": "Cellular gluconeogenesis by lactating bovine mammary tissue.", "content": "The gluconeogenic capacity of mammary tissue of lactating cow was investigated by incubating mammary tissue slices with alanine, glutamate, lactate, pyruvate, or glycerol in conjunction with acetate and glucose (10mM or 1 mM). In no case was any substrate incorporated into glucose per se. In lactose synthesis, glucose was the major source of carbon although glycerol also was incorporated into lactose. Alanine, glutamate, lactate, or pyruvate were not incorporated into lactose at optimum (10 mM) or suboptimum (1 mM) concentrations of glucose. Activity of glucose-6-phosphatase was negligible in mammary tissue, less than 1% of the activity in liver or kidney tissue from the same cows. Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and fructose-1,6-diphosphatase were in cow mammary tissue, but the activities were lower than in liver. Gluconeogenic substrates were not converted to glucose regardless of whether the incubation contained an optimum (10 mM) or a suboptimum (1 mM) glucose concentration. Consistent with the inability of cow mammary tissue to convert gluconeogenic metabolites to glucose is the virtual absence of glucose-6-phosphatase and the lack of excess gluconeogenic substrates available to the intact mammary gland of lactating cow.", "contents": "Cellular gluconeogenesis by lactating bovine mammary tissue. The gluconeogenic capacity of mammary tissue of lactating cow was investigated by incubating mammary tissue slices with alanine, glutamate, lactate, pyruvate, or glycerol in conjunction with acetate and glucose (10mM or 1 mM). In no case was any substrate incorporated into glucose per se. In lactose synthesis, glucose was the major source of carbon although glycerol also was incorporated into lactose. Alanine, glutamate, lactate, or pyruvate were not incorporated into lactose at optimum (10 mM) or suboptimum (1 mM) concentrations of glucose. Activity of glucose-6-phosphatase was negligible in mammary tissue, less than 1% of the activity in liver or kidney tissue from the same cows. Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and fructose-1,6-diphosphatase were in cow mammary tissue, but the activities were lower than in liver. Gluconeogenic substrates were not converted to glucose regardless of whether the incubation contained an optimum (10 mM) or a suboptimum (1 mM) glucose concentration. Consistent with the inability of cow mammary tissue to convert gluconeogenic metabolites to glucose is the virtual absence of glucose-6-phosphatase and the lack of excess gluconeogenic substrates available to the intact mammary gland of lactating cow."} {"id": "PMID:175104", "title": "Determination of physical properties of bovine serum lipoproteins by analytical ultracentrifugation.", "content": "Pure samples of low density lipoprotein-one (d 1.019 to 1.039 g/ml), low density lipoprotein-two (d 1.039 to 1.060 g/ml), and high density lipoprotein (d 1.060 to 1.210 g/ml) were isolated from bovine serum and their properties studied in the analytical ultracentrifuge. Approach-to-equilibrium experiments indicated that the lipoprotein classes were homogeneous. Molecular weights of the lipoproteins given by this method (low density lipoprotein-one, 1.14 x 10(6); low density lipoprotein-two, 2.37 x 10(6); high density lipoprotein, .576 x 10(6)) agreed well with those obtained by a high-speed-equilibrium method (1.03 x 10(6), 2.15 x 10(6), and .567 x 10(6)). Linear plots of flotation rate (corrected for viscosity) against the density of the medium were obtained in sedimentation velocity experiments and on extrapolation gave values for the hydrated density of 1.032 g/ml for low density lipoprotein-one, 1.044 g/ml for low density lipoprotein-two, and 1.071 g/ml for high density lipoprotein. The density of the material which would have to be added to high density lipoprotein to give it the physical properties of low density lipoprotein one was less than 1 g/ml, which suggested that it was predominantly lipid.", "contents": "Determination of physical properties of bovine serum lipoproteins by analytical ultracentrifugation. Pure samples of low density lipoprotein-one (d 1.019 to 1.039 g/ml), low density lipoprotein-two (d 1.039 to 1.060 g/ml), and high density lipoprotein (d 1.060 to 1.210 g/ml) were isolated from bovine serum and their properties studied in the analytical ultracentrifuge. Approach-to-equilibrium experiments indicated that the lipoprotein classes were homogeneous. Molecular weights of the lipoproteins given by this method (low density lipoprotein-one, 1.14 x 10(6); low density lipoprotein-two, 2.37 x 10(6); high density lipoprotein, .576 x 10(6)) agreed well with those obtained by a high-speed-equilibrium method (1.03 x 10(6), 2.15 x 10(6), and .567 x 10(6)). Linear plots of flotation rate (corrected for viscosity) against the density of the medium were obtained in sedimentation velocity experiments and on extrapolation gave values for the hydrated density of 1.032 g/ml for low density lipoprotein-one, 1.044 g/ml for low density lipoprotein-two, and 1.071 g/ml for high density lipoprotein. The density of the material which would have to be added to high density lipoprotein to give it the physical properties of low density lipoprotein one was less than 1 g/ml, which suggested that it was predominantly lipid."} {"id": "PMID:175106", "title": "Evaluation of pituitary-adrenal function in patients with chronic bronchial asthma following substitution of steroid treatment with disodium cromoglycate (Lomudal).", "content": "In a group of 32 steroid-dependent asthmatic patients an attempt was made to replace steroid treatment with disodium cromoglycate (Lomudal). Withdrawal of steroids was accompanied by a transitory stage of combined corticotropin-Lomudal treatment for 6 to 8 mo. Pituitary-adrenal function was assessed by ACTH and Metopirone test. Before treatment an impairment of pituitary-adrenal function was found in most of our patients, although in 26 patients a normal increment of plasma cortisol was found after ACTH stimulation. At the end of the combined treatment, 17 patients are now on Lomudal with normal pituitary-adrenal function, 9 patients need small quantities of steroids occasionally, and 6 patients are steroid-dependent.", "contents": "Evaluation of pituitary-adrenal function in patients with chronic bronchial asthma following substitution of steroid treatment with disodium cromoglycate (Lomudal). In a group of 32 steroid-dependent asthmatic patients an attempt was made to replace steroid treatment with disodium cromoglycate (Lomudal). Withdrawal of steroids was accompanied by a transitory stage of combined corticotropin-Lomudal treatment for 6 to 8 mo. Pituitary-adrenal function was assessed by ACTH and Metopirone test. Before treatment an impairment of pituitary-adrenal function was found in most of our patients, although in 26 patients a normal increment of plasma cortisol was found after ACTH stimulation. At the end of the combined treatment, 17 patients are now on Lomudal with normal pituitary-adrenal function, 9 patients need small quantities of steroids occasionally, and 6 patients are steroid-dependent."} {"id": "PMID:175115", "title": "Histochemistry of neuronal degenerative changes.", "content": "Classical forms of degenerative changes of neurocytes, defined by Nissl and Spielmeyer as neuronal diseases were produced experimentally in rats. The individual neuronal changes were induced with the aid of X-ray irradiation, TET administration, ligation of the carotid artery followed by oxygen deficient breathing (anoxia), and by sectioning of the sciatic nerve. The so produced experimental models of neuronal diseases were the subject of morphological and cytochemical studies with special attention payed to enzymic and autoradiographic reactivity. Basing on the results of performed investigations, the author inferred that from a pathogenetic point of view, not all of the respective forms of neuronal diseases postulated by the classification of Nissl and Spielmeyer can be regarded as separate, distinct forms of degenerative changes. From the results obtained it would appear that pathogenetically distinct are only the following diseases: acute nerve cell swelling, shrinkage of perikaryons, homogenizing changes of Purkinje cells and axonal degeneration. The so called severe disease as well as the ischemic disease should be regarded as transitory forms of neuronal changes developing from shrunken neurocytes. It has also been suggested that the pathogenesis of homogenizing changes in Purkinje cells is distinct from that responsible for the development of ischemic changes in the course of cerebral anoxia and ischemia. This suggestion is substantiated by the observed differences in cytoenzymic reactivity between homogenized Purkinje cells and ischemically changed neurocytes.", "contents": "Histochemistry of neuronal degenerative changes. Classical forms of degenerative changes of neurocytes, defined by Nissl and Spielmeyer as neuronal diseases were produced experimentally in rats. The individual neuronal changes were induced with the aid of X-ray irradiation, TET administration, ligation of the carotid artery followed by oxygen deficient breathing (anoxia), and by sectioning of the sciatic nerve. The so produced experimental models of neuronal diseases were the subject of morphological and cytochemical studies with special attention payed to enzymic and autoradiographic reactivity. Basing on the results of performed investigations, the author inferred that from a pathogenetic point of view, not all of the respective forms of neuronal diseases postulated by the classification of Nissl and Spielmeyer can be regarded as separate, distinct forms of degenerative changes. From the results obtained it would appear that pathogenetically distinct are only the following diseases: acute nerve cell swelling, shrinkage of perikaryons, homogenizing changes of Purkinje cells and axonal degeneration. The so called severe disease as well as the ischemic disease should be regarded as transitory forms of neuronal changes developing from shrunken neurocytes. It has also been suggested that the pathogenesis of homogenizing changes in Purkinje cells is distinct from that responsible for the development of ischemic changes in the course of cerebral anoxia and ischemia. This suggestion is substantiated by the observed differences in cytoenzymic reactivity between homogenized Purkinje cells and ischemically changed neurocytes."} {"id": "PMID:175116", "title": "Does Freund's adjuvant denature protein antigens? EPR studies of emulsified hemoglobin.", "content": "Use of complete Freund's adjuvant for production of antibodies to study protein conformation is valid only if emulsification in adjuvant does not denature protein antigens. Using electron paramagnetic resonance to observe directly the protein in situ in the opaque emulsions, we demonstrate that hemoglobin is not denatured by emulsification or storage in adjuvant for 24 hr at 4 degrees C, conditions comparable to the usual handling of antigens before immunization.", "contents": "Does Freund's adjuvant denature protein antigens? EPR studies of emulsified hemoglobin. Use of complete Freund's adjuvant for production of antibodies to study protein conformation is valid only if emulsification in adjuvant does not denature protein antigens. Using electron paramagnetic resonance to observe directly the protein in situ in the opaque emulsions, we demonstrate that hemoglobin is not denatured by emulsification or storage in adjuvant for 24 hr at 4 degrees C, conditions comparable to the usual handling of antigens before immunization."} {"id": "PMID:175117", "title": "A microtiter solid-phase radioimmunoassay for hepatitis A antigen and antibody.", "content": "A microtiter solid phase radioimmunoassy for hepatitis A antigen (HA Ag) and antibody (anti-HA) was developed. The test was more sensitive than immune adherence hemagglutination for detecting HA Ag and almost as sensitive for detecting anti-HA. The specificity and sensitivity of reagents were examined and optimum conditions for the test were determined. Radioimmunoassay, immune adherence hemagglutination, and immune electron microscopy were compared for detecting anti-HA. A serologic response to HA Ag was detected in paired sera from patients with type A hepatitis but not from patients with type B or non-A, non-B hepatitis by all three techniques.", "contents": "A microtiter solid-phase radioimmunoassay for hepatitis A antigen and antibody. A microtiter solid phase radioimmunoassy for hepatitis A antigen (HA Ag) and antibody (anti-HA) was developed. The test was more sensitive than immune adherence hemagglutination for detecting HA Ag and almost as sensitive for detecting anti-HA. The specificity and sensitivity of reagents were examined and optimum conditions for the test were determined. Radioimmunoassay, immune adherence hemagglutination, and immune electron microscopy were compared for detecting anti-HA. A serologic response to HA Ag was detected in paired sera from patients with type A hepatitis but not from patients with type B or non-A, non-B hepatitis by all three techniques."} {"id": "PMID:175113", "title": "[Histoenzymologic modifications of placental tissue in experimental fetal hypotrophy in the rat].", "content": "Chronic placental vascular insufficiency in the rat was achieved by ligature of the uterine and utero-placental arteries. The fetal and placental hypotrophy observed confirmed the previous observation. However, the placental enzymatic changes showed an increasing gradient of cellular hypoxy from decidua basalis to yolk sac placenta; this gradient is unfavourable to fetuses. The strong depletion of yolk sac enzyme activities demonstrates the reduction of fetomaternal exchanges which are usually predominant in this placental area. The other parts of rat placenta appear relatively less involved in fetal nutrition. Further studies are necessary to understand the changes observed in these activity stainings, such as: oxidoreductases II, acid phosphatase and 5-nucleotidase.", "contents": "[Histoenzymologic modifications of placental tissue in experimental fetal hypotrophy in the rat]. Chronic placental vascular insufficiency in the rat was achieved by ligature of the uterine and utero-placental arteries. The fetal and placental hypotrophy observed confirmed the previous observation. However, the placental enzymatic changes showed an increasing gradient of cellular hypoxy from decidua basalis to yolk sac placenta; this gradient is unfavourable to fetuses. The strong depletion of yolk sac enzyme activities demonstrates the reduction of fetomaternal exchanges which are usually predominant in this placental area. The other parts of rat placenta appear relatively less involved in fetal nutrition. Further studies are necessary to understand the changes observed in these activity stainings, such as: oxidoreductases II, acid phosphatase and 5-nucleotidase."} {"id": "PMID:175118", "title": "Neuraminidase reversal of resistance to lysis of herpes simplex virus-infected cells by antibody and complement.", "content": "The susceptibility to lysis by antibody and complement was examined in four human cell lines. The cells were infected with herpes simplex virus type 1 and lysis was assessed by the 51Cr release test by using antibodies to herpes simplex virus and guinea pig serum as a source of complement. The four cell lines were found to differ in their susceptibility to lysis, although virus replication was readily demonstrated in the different cell lines. By indirect immunofluorescence, no differences in the expression of virus antigens at the surface of the cells could be found between the different cell lines. Treatment of cells with neuraminidase markedly enhanced the sensitivity of the cells which were relatively insensitive to lysis. The enhancement of susceptibiltiy to lysis by neuraminidase occurred if cells were treated before reaction of the cells with antibody and if the cells were reacted with antibody before treatment with the enzyme. No enhancement was observed when cells were reacted with antibody and complement before neuraminidase treatment. Neuraminidase treatment did not seem to enhance appreciably the quantity of antibody which reacted at the cell surface. The observations suggest that surface properties of certain cells render the cells resistant to lysis by antibody and complement and that the resistance to lysis can be abrogated by treating the cells with neuraminidase.", "contents": "Neuraminidase reversal of resistance to lysis of herpes simplex virus-infected cells by antibody and complement. The susceptibility to lysis by antibody and complement was examined in four human cell lines. The cells were infected with herpes simplex virus type 1 and lysis was assessed by the 51Cr release test by using antibodies to herpes simplex virus and guinea pig serum as a source of complement. The four cell lines were found to differ in their susceptibility to lysis, although virus replication was readily demonstrated in the different cell lines. By indirect immunofluorescence, no differences in the expression of virus antigens at the surface of the cells could be found between the different cell lines. Treatment of cells with neuraminidase markedly enhanced the sensitivity of the cells which were relatively insensitive to lysis. The enhancement of susceptibiltiy to lysis by neuraminidase occurred if cells were treated before reaction of the cells with antibody and if the cells were reacted with antibody before treatment with the enzyme. No enhancement was observed when cells were reacted with antibody and complement before neuraminidase treatment. Neuraminidase treatment did not seem to enhance appreciably the quantity of antibody which reacted at the cell surface. The observations suggest that surface properties of certain cells render the cells resistant to lysis by antibody and complement and that the resistance to lysis can be abrogated by treating the cells with neuraminidase."} {"id": "PMID:175119", "title": "Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti-hapten antibody response to anti-immunoglobulin and enhancing soluble factor.", "content": "The effect of elevation of an intracellular cyclic AMP level on in vitro anti-hapten antibody response was studied, by using mesenteric lymph node cells of rabbits which were primed with dinitrophenylated Ascaris antigen (DNP-Asc) or DNP-ragweed antigen (DNP-Rag). The anti-hapten antibody response was induced by stimulation of the primed B cells by either DNP-heterologous carrier conjugate or anti-immunoglobulin (anti-Ig) for 24 hr (first stage), followed by 6-day culture of the activated cells in the presence of nonspecific enhancing factor (second stage). The stimulation with anti-Ig induced IgG anti-hapten antibody response and enhanced the formation of total IgG. Addition of dibutyryl cyclic AMP or aminophylline with anti-Ig or DNP-heterologous carrier during the first stage enhanced IgG anti-hapten antibody response. The optimal concentration of these reagents for the enhancement was 5 x 10(-4) M to 10(-3) M. The presence of 5 x 10(-6) M prostaglandin E1 during the first stage also enhanced the antibody response. Similarly, the presence of dibutyryl cyclic AMP or aminophylline during the stimulation of DNP-Rag-primed cells with homologous antigen (first stage) enhanced the antibody response. If the same concentration of dibutyryl cyclic AMP or aminophylline was added together with enhancing soluble factor during the second stage after the stimulation of the primed cells with anti-Ig, both the antibody response and the formation of IgG were suppressed. The antibody response of DNP-Rag-primed cells stimulated with homologous antigen was also suppressed if dibutyryl cyclic AMP or aminophylline was added during the subsequent culture (second stage). Evidence was obtained that suppression of antibody response by cyclic AMP during the second stage is probably due to inhibition of the proliferation of B cells. Neither of these drugs suppressed the formation of enhancing soluble factor from the carrier-specific cells stimulated with the homologous carrier. The results obtained in the present experiments suggested that stimulation of hapten-primed B cells with anti-gamma chain in the presence of an optimal concentration of dibutyryl cyclic AMP resulted in the formation of a significant amount of IgG anti-DNP antibody without participation of T cells.", "contents": "Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti-hapten antibody response to anti-immunoglobulin and enhancing soluble factor. The effect of elevation of an intracellular cyclic AMP level on in vitro anti-hapten antibody response was studied, by using mesenteric lymph node cells of rabbits which were primed with dinitrophenylated Ascaris antigen (DNP-Asc) or DNP-ragweed antigen (DNP-Rag). The anti-hapten antibody response was induced by stimulation of the primed B cells by either DNP-heterologous carrier conjugate or anti-immunoglobulin (anti-Ig) for 24 hr (first stage), followed by 6-day culture of the activated cells in the presence of nonspecific enhancing factor (second stage). The stimulation with anti-Ig induced IgG anti-hapten antibody response and enhanced the formation of total IgG. Addition of dibutyryl cyclic AMP or aminophylline with anti-Ig or DNP-heterologous carrier during the first stage enhanced IgG anti-hapten antibody response. The optimal concentration of these reagents for the enhancement was 5 x 10(-4) M to 10(-3) M. The presence of 5 x 10(-6) M prostaglandin E1 during the first stage also enhanced the antibody response. Similarly, the presence of dibutyryl cyclic AMP or aminophylline during the stimulation of DNP-Rag-primed cells with homologous antigen (first stage) enhanced the antibody response. If the same concentration of dibutyryl cyclic AMP or aminophylline was added together with enhancing soluble factor during the second stage after the stimulation of the primed cells with anti-Ig, both the antibody response and the formation of IgG were suppressed. The antibody response of DNP-Rag-primed cells stimulated with homologous antigen was also suppressed if dibutyryl cyclic AMP or aminophylline was added during the subsequent culture (second stage). Evidence was obtained that suppression of antibody response by cyclic AMP during the second stage is probably due to inhibition of the proliferation of B cells. Neither of these drugs suppressed the formation of enhancing soluble factor from the carrier-specific cells stimulated with the homologous carrier. The results obtained in the present experiments suggested that stimulation of hapten-primed B cells with anti-gamma chain in the presence of an optimal concentration of dibutyryl cyclic AMP resulted in the formation of a significant amount of IgG anti-DNP antibody without participation of T cells."} {"id": "PMID:175120", "title": "Cell mediated immunity to herpes simplex in man. IV. A correlation of lymphocyte stimulation and inhibition of leukocyte migration.", "content": "The cell mediated immune response to herpes simplex virus was assessed by a modification of the leukocyte migration inhibition test, developed to increase its sensitivity and correlated with the in vitro stimulation of lymphocytes. The introduction of a preincubation step allowed us to demonstrate significant inhibition of leukocyte migration in 15 out of 24 subjects susceptible to recurrent herpes labialis. This was not present in any of the 10 subjects without such infections. However lymphocytes from all 24 subjects demonstrated stimulation in response to herpes virus antigen. The degrees of lymphocyte stimulation and migration inhibition in the susceptible subjects were well correlated and do not support the suggestion that there is a focal defect in this aspect of the cell mediated immune response to herpes simplex virus in those patients.", "contents": "Cell mediated immunity to herpes simplex in man. IV. A correlation of lymphocyte stimulation and inhibition of leukocyte migration. The cell mediated immune response to herpes simplex virus was assessed by a modification of the leukocyte migration inhibition test, developed to increase its sensitivity and correlated with the in vitro stimulation of lymphocytes. The introduction of a preincubation step allowed us to demonstrate significant inhibition of leukocyte migration in 15 out of 24 subjects susceptible to recurrent herpes labialis. This was not present in any of the 10 subjects without such infections. However lymphocytes from all 24 subjects demonstrated stimulation in response to herpes virus antigen. The degrees of lymphocyte stimulation and migration inhibition in the susceptible subjects were well correlated and do not support the suggestion that there is a focal defect in this aspect of the cell mediated immune response to herpes simplex virus in those patients."} {"id": "PMID:175122", "title": "Turnover of xanthoma cholesterol in hyperlipoproteinemia patients.", "content": "The turnover of xanthoma cholesterol was measured in 9 hyperlipidemic and one normocholesterolemic patients. Sequential biopsies of the xanthomas were obtained 13 to 364 days after the administration of isotopic cholesterol and were then analyzed for cholesterol specific activity. A total of 34 xanthomas of 3 different types - 10 tendon xanthomas, 3 tuberous xanthomas, and 21 xanthelasmas - comprised the material for analysis. The cholesterol specific activity ratio of tendron xanthomas to that of the plasma varied from 11 per cent at 21 days to a maximum of 543 per cent at 122 days after the intravenous administration of isotopic cholesterol. This ratio declined to 426 per cent at 182 days and was still 131 per cent at 364 days. Similarly, the cholesterol specific activity of xanthelasmas increased gradually. In most instances, the xanthelasma cholesterol attained isotopic equilibration with plasma cholesterol by about 50 days but varied from patient to patient (minimum time, 46 days and maximum time, 91 days). The cholesterol content of xanthomas ranged from 10.7 to 197.0 mg per gram of dry weight of the tissue. Sixty-one to 87 per cent of the total xanthoma cholesterol was esterified. No other sterols were identified in these xanthomas. Thus, the cholesterol of 3 types of xanthoma readily attained isotopic equilibration with the plasma cholesterol which suggested total exchangeability of cholesterol between plasma and xanthomas. The uptake of cholesterol by the xanthomas from plasma was rapid considering the large mass of cholesterol in the lesions. The turnover of xanthoma cholesterol was intermediate between that of the rapidly exchangeable pool and of the slowly exchangeable pool of body cholesterol. Comparison of these results with those obtained in human advanced atheroma suggest that the turnover of xanthoma cholesterol and atheroma cholesterol are quite different.", "contents": "Turnover of xanthoma cholesterol in hyperlipoproteinemia patients. The turnover of xanthoma cholesterol was measured in 9 hyperlipidemic and one normocholesterolemic patients. Sequential biopsies of the xanthomas were obtained 13 to 364 days after the administration of isotopic cholesterol and were then analyzed for cholesterol specific activity. A total of 34 xanthomas of 3 different types - 10 tendon xanthomas, 3 tuberous xanthomas, and 21 xanthelasmas - comprised the material for analysis. The cholesterol specific activity ratio of tendron xanthomas to that of the plasma varied from 11 per cent at 21 days to a maximum of 543 per cent at 122 days after the intravenous administration of isotopic cholesterol. This ratio declined to 426 per cent at 182 days and was still 131 per cent at 364 days. Similarly, the cholesterol specific activity of xanthelasmas increased gradually. In most instances, the xanthelasma cholesterol attained isotopic equilibration with plasma cholesterol by about 50 days but varied from patient to patient (minimum time, 46 days and maximum time, 91 days). The cholesterol content of xanthomas ranged from 10.7 to 197.0 mg per gram of dry weight of the tissue. Sixty-one to 87 per cent of the total xanthoma cholesterol was esterified. No other sterols were identified in these xanthomas. Thus, the cholesterol of 3 types of xanthoma readily attained isotopic equilibration with the plasma cholesterol which suggested total exchangeability of cholesterol between plasma and xanthomas. The uptake of cholesterol by the xanthomas from plasma was rapid considering the large mass of cholesterol in the lesions. The turnover of xanthoma cholesterol was intermediate between that of the rapidly exchangeable pool and of the slowly exchangeable pool of body cholesterol. Comparison of these results with those obtained in human advanced atheroma suggest that the turnover of xanthoma cholesterol and atheroma cholesterol are quite different."} {"id": "PMID:175123", "title": "A study on the reactions of tubercidin triphosphate with myosin and actomyosin.", "content": "The triphosphate ester of tubercidin (tubercidin triphosphate, TuTP) was synthesized. This is an analog of ATP in which a CH group replaces the N-7 of the adenine ring. The rate of TuTP hydrolysis by myosin in the presence of Mg2+ was the same as that of ATP in the 10(-7)-10(-3) M range, whereas the increment in the optical density of myosin ihe 290mmu region caused by TuTP was twice that caused by ATP. TuTP is hydrolyzed by actomyosin faster than ATP, the value of Vmax being about 4 times larger while the Km values were of the same order of magnitude. The rate of superprecipitation induced by TuTP was 50% of that caused by ATP at nucleotide concentrations of 3-60 muM. A similar difference was observed with respect to the rate of tension development by glycerol-extracted rabbit psoas fibers upon addition of these two substances. Substitution of ADP by tubercidin diphosphate (TuDP) in F-actin did not affect the rate of superprecipitation or enzymic activity of actomyosin.", "contents": "A study on the reactions of tubercidin triphosphate with myosin and actomyosin. The triphosphate ester of tubercidin (tubercidin triphosphate, TuTP) was synthesized. This is an analog of ATP in which a CH group replaces the N-7 of the adenine ring. The rate of TuTP hydrolysis by myosin in the presence of Mg2+ was the same as that of ATP in the 10(-7)-10(-3) M range, whereas the increment in the optical density of myosin ihe 290mmu region caused by TuTP was twice that caused by ATP. TuTP is hydrolyzed by actomyosin faster than ATP, the value of Vmax being about 4 times larger while the Km values were of the same order of magnitude. The rate of superprecipitation induced by TuTP was 50% of that caused by ATP at nucleotide concentrations of 3-60 muM. A similar difference was observed with respect to the rate of tension development by glycerol-extracted rabbit psoas fibers upon addition of these two substances. Substitution of ADP by tubercidin diphosphate (TuDP) in F-actin did not affect the rate of superprecipitation or enzymic activity of actomyosin."} {"id": "PMID:175125", "title": "In vitro study of chorionic and ectoplacental trophoblast differentiation in the mouse.", "content": "Mouse chorioallantoic pre-placental structures alone or in association with the embryo were explanted during the 9th day of gestation (7-somite stage) and cultured in a static medium for 24 to 48 h. From the subsequent morphological study of trophoblast differentiation, using both light and electron microscopy, we draw the following conclusions. 1. The allantoic mesoderm cells migrate inside the trophoblastic population but they do not differentiate a capillary network and trophoblast cells phagocytose the existing foetal erythrocytes. 2. In the absence of allantoic mesoderm, chorionic trophoblast cells remain undifferentiated. 3. The development of the chorionic trophoblast is modified in that chorionic trophoblast cells fail to establish close junctions with ectoplacental trophoblast, and some chorionic cells initiate the formation of multinucleated syncytia. The genesis of these syncytia is discussed.", "contents": "In vitro study of chorionic and ectoplacental trophoblast differentiation in the mouse. Mouse chorioallantoic pre-placental structures alone or in association with the embryo were explanted during the 9th day of gestation (7-somite stage) and cultured in a static medium for 24 to 48 h. From the subsequent morphological study of trophoblast differentiation, using both light and electron microscopy, we draw the following conclusions. 1. The allantoic mesoderm cells migrate inside the trophoblastic population but they do not differentiate a capillary network and trophoblast cells phagocytose the existing foetal erythrocytes. 2. In the absence of allantoic mesoderm, chorionic trophoblast cells remain undifferentiated. 3. The development of the chorionic trophoblast is modified in that chorionic trophoblast cells fail to establish close junctions with ectoplacental trophoblast, and some chorionic cells initiate the formation of multinucleated syncytia. The genesis of these syncytia is discussed."} {"id": "PMID:175126", "title": "Regulation of the T-cell response to ectromelia virus infection. I. Feedback suppression by effector T cells.", "content": "Spleen cells and serum from mice immunized with ectromelia virus suppressed the immune response to infectious virus when transferred intravenously into recipient mice given an immunizing virus dose. The suppression was reflected in decreased cytotoxic T-cell activity directed against H-2 compatible virus-infected target cells in the spleens of recipients. Suppression was observed when immune cells or serum were transferred 1-2 h or 1 day after immunization of recipients, but not 2 days after, and was maximal when 6-day immune spleen cells were used as suppressor cells. H-2 compatibility between donor and recipient mice was necessary for suppression to be expressed. Use of recombinant mice showed that I-region compatibility was neither sufficient nor necessary, and that D-region compatibility was sufficient. Specificity of suppression was suggested by the finding that cells and serum from mice immunized with Listeria monocytogenes, a bacterium, had no suppressive activity on the antiviral response. Anti-theta treatment eliminated the ability of immune cells to suppress, and the suppressive effect was not markedly dose-dependent with respect to both cell dose and virus dose under the conditions employed. Virus levels in the spleens of recipients were significantly reduced after injection of immune cells. Adult thymectomy had no effect on the primary immune response to ectromelia virus infection, thus indicating no role for T1 cells in the suppressive mechanism. The results obtained therefore suggested that suppression in this system was due to effector T cells which triggered clearance of virus (and thus, of virus-induced antigens) necessary for the induction of precursors of effector T cells, and that this simple feed-back mechanism normally plays an important role in the regulation of the primary immune response to ectromelia infection at the level of precursor induction. The existence of other postinduction regulatory mechanisms, however, is unknown and under investigation.", "contents": "Regulation of the T-cell response to ectromelia virus infection. I. Feedback suppression by effector T cells. Spleen cells and serum from mice immunized with ectromelia virus suppressed the immune response to infectious virus when transferred intravenously into recipient mice given an immunizing virus dose. The suppression was reflected in decreased cytotoxic T-cell activity directed against H-2 compatible virus-infected target cells in the spleens of recipients. Suppression was observed when immune cells or serum were transferred 1-2 h or 1 day after immunization of recipients, but not 2 days after, and was maximal when 6-day immune spleen cells were used as suppressor cells. H-2 compatibility between donor and recipient mice was necessary for suppression to be expressed. Use of recombinant mice showed that I-region compatibility was neither sufficient nor necessary, and that D-region compatibility was sufficient. Specificity of suppression was suggested by the finding that cells and serum from mice immunized with Listeria monocytogenes, a bacterium, had no suppressive activity on the antiviral response. Anti-theta treatment eliminated the ability of immune cells to suppress, and the suppressive effect was not markedly dose-dependent with respect to both cell dose and virus dose under the conditions employed. Virus levels in the spleens of recipients were significantly reduced after injection of immune cells. Adult thymectomy had no effect on the primary immune response to ectromelia virus infection, thus indicating no role for T1 cells in the suppressive mechanism. The results obtained therefore suggested that suppression in this system was due to effector T cells which triggered clearance of virus (and thus, of virus-induced antigens) necessary for the induction of precursors of effector T cells, and that this simple feed-back mechanism normally plays an important role in the regulation of the primary immune response to ectromelia infection at the level of precursor induction. The existence of other postinduction regulatory mechanisms, however, is unknown and under investigation."} {"id": "PMID:175127", "title": "Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages.", "content": "Genetic resistance to mouse hepatitis, which resides largely in the macrophages of resistant C3H mice, may be altered by exposing the cells in vitro to fluid from allogeneic mixed lymphocytes. A 1,000-fold increase in susceptibility was produced in these genetically resistant cells by exposure to this fluid. This presumed lymphokine was effective without producing any change in host adaption of the virus.", "contents": "Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages. Genetic resistance to mouse hepatitis, which resides largely in the macrophages of resistant C3H mice, may be altered by exposing the cells in vitro to fluid from allogeneic mixed lymphocytes. A 1,000-fold increase in susceptibility was produced in these genetically resistant cells by exposure to this fluid. This presumed lymphokine was effective without producing any change in host adaption of the virus."} {"id": "PMID:175128", "title": "Influence of auxiliary enzymes on the spectrophotometric measurement of alanine aminotransferase and aspartate aminotransferase activities.", "content": "We investigated the enzyme activity of the blank in the spectrophotometric determination of the aminotransferase activities and aspartate aminotransferase activity. 6 lactate dehydrogenase and 3 malate dehydrogenase preparations from different manufactures and from different organs showed additional and contaminating activity. The additional activity depends upon the 2-oxoglutarate concentration. The contaminating activity is caused by alanine aminotransferase and aspartate aminotransferase in the auxiliary enzymes. We propose that exact definitions must be given for the auxiliary enzymes in the recommendations of standard determinations for enzyme activities.", "contents": "Influence of auxiliary enzymes on the spectrophotometric measurement of alanine aminotransferase and aspartate aminotransferase activities. We investigated the enzyme activity of the blank in the spectrophotometric determination of the aminotransferase activities and aspartate aminotransferase activity. 6 lactate dehydrogenase and 3 malate dehydrogenase preparations from different manufactures and from different organs showed additional and contaminating activity. The additional activity depends upon the 2-oxoglutarate concentration. The contaminating activity is caused by alanine aminotransferase and aspartate aminotransferase in the auxiliary enzymes. We propose that exact definitions must be given for the auxiliary enzymes in the recommendations of standard determinations for enzyme activities."} {"id": "PMID:175129", "title": "[Specificity of 3 alpha, 20 beta-hydroxysteroid: nad+ -oxidoreductase (author's transl)].", "content": "The enzyme 3 alpha, 20 beta-hydroxysteroid:NAD+ oxidoreductase (EC 1.1.1.53) catalyses the stoichiometric reduction of 20-oxo groups of C-21 steroids by NADH, and the non-stoichiometric oxidation of 3 alpha-hydroxy groups of 5 alpha-androstane derivatives by NAD. The activity of the enzyme towards the most important C-18, C-19 and C-21 steroids of human urine was tested in the presence of NAD and NADH. The rate of reduction of 20-oxo steroids is influenced by substituents at various positions of the steroid skeleton. These studies are intended as the basis of an eventual clinical chemical application.", "contents": "[Specificity of 3 alpha, 20 beta-hydroxysteroid: nad+ -oxidoreductase (author's transl)]. The enzyme 3 alpha, 20 beta-hydroxysteroid:NAD+ oxidoreductase (EC 1.1.1.53) catalyses the stoichiometric reduction of 20-oxo groups of C-21 steroids by NADH, and the non-stoichiometric oxidation of 3 alpha-hydroxy groups of 5 alpha-androstane derivatives by NAD. The activity of the enzyme towards the most important C-18, C-19 and C-21 steroids of human urine was tested in the presence of NAD and NADH. The rate of reduction of 20-oxo steroids is influenced by substituents at various positions of the steroid skeleton. These studies are intended as the basis of an eventual clinical chemical application."} {"id": "PMID:175131", "title": "[Phakomatoses. Ophthalmological and genetic aspects].", "content": "Detailed ophthalmological and genetic studies on the four classical types of phacomatoses and more succint studies of twelve syndromes which can be considered as atypical forms of phacomatoses. Discussion of the association between the different forms of phacomatoses. Establishment of genetic prognoses.", "contents": "[Phakomatoses. Ophthalmological and genetic aspects]. Detailed ophthalmological and genetic studies on the four classical types of phacomatoses and more succint studies of twelve syndromes which can be considered as atypical forms of phacomatoses. Discussion of the association between the different forms of phacomatoses. Establishment of genetic prognoses."} {"id": "PMID:175133", "title": "Non-hypertrophic familial neuropathy associated with intention tremor. A variety of Charcot-Marie-Tooth disease?", "content": "A family with an association of sensorimotor neuropathy and intention tremor is reported. Clinical examination of 3 affected family members showed in varying degrees areflexia, muscle wasting, impairment of deep sensation with an ataxic gait, pes cavus and disabling intention tremor. Motor nerve conduction velocities were moderately slowed. A superficial peroneal nerve biopsy showed axonal degeneration without segmental demyelination or onion bulb formation. Our observation seems to indicate an association of intention tremor with the non-hypertrophic variety of Charcot-Marie-Tooth disease. It can therefore be suggested that the two classical types of Charcot-Marie-Tooth syndrome possess variants which are associated with intention tremor. This association is well-known for the hypertrophic type; our report gives an example of the non-hypertrophic type.", "contents": "Non-hypertrophic familial neuropathy associated with intention tremor. A variety of Charcot-Marie-Tooth disease? A family with an association of sensorimotor neuropathy and intention tremor is reported. Clinical examination of 3 affected family members showed in varying degrees areflexia, muscle wasting, impairment of deep sensation with an ataxic gait, pes cavus and disabling intention tremor. Motor nerve conduction velocities were moderately slowed. A superficial peroneal nerve biopsy showed axonal degeneration without segmental demyelination or onion bulb formation. Our observation seems to indicate an association of intention tremor with the non-hypertrophic variety of Charcot-Marie-Tooth disease. It can therefore be suggested that the two classical types of Charcot-Marie-Tooth syndrome possess variants which are associated with intention tremor. This association is well-known for the hypertrophic type; our report gives an example of the non-hypertrophic type."} {"id": "PMID:175134", "title": "Congenital oculoskeletal myopathy with abnormal muscle and liver mitochondria.", "content": "We report a 22-year-old very thin man, who showed various symptoms and signs of oculoskeletal muscle weakness, episodes of myalgia, prolonged diarrhea, severe myopia, perceptive deafness, electrocardiographic and electroencephalographic abnormalities, and endocrinological abnormality. The onset was at about 3 months of age and a positive family history was strongly suggested. The light-microscopic, histochemical and electron-microscopic findings showed abnormal mitochondria not only in the skeletal muscle, but also in liver cells. From the clinical as well as morphological points of view, this case was suspected to be one of congenital oculoskeletal myopathy probably due to an unidentified systemic metabolic disorder.", "contents": "Congenital oculoskeletal myopathy with abnormal muscle and liver mitochondria. We report a 22-year-old very thin man, who showed various symptoms and signs of oculoskeletal muscle weakness, episodes of myalgia, prolonged diarrhea, severe myopia, perceptive deafness, electrocardiographic and electroencephalographic abnormalities, and endocrinological abnormality. The onset was at about 3 months of age and a positive family history was strongly suggested. The light-microscopic, histochemical and electron-microscopic findings showed abnormal mitochondria not only in the skeletal muscle, but also in liver cells. From the clinical as well as morphological points of view, this case was suspected to be one of congenital oculoskeletal myopathy probably due to an unidentified systemic metabolic disorder."} {"id": "PMID:175135", "title": "Characteristics of myosin in nemaline myopathy.", "content": "Electron-microscopic, morphometric, histochemical and biochemical studies were carried out on muscle biopsies from a patient with the characteristic clinical and pathological findings of nemaline myopathy. The mean fiber diameter was decreased, and the vastus lateralis muscle biopsy consisted exclusively of slow twitch (Type I) fibers. Quantitative biochemical investigations revealed significantly low calcium uptake and ATPase activity of the fragmented sarcoplasmic reticulum and decreased myosin ATPase activity. The electrophoretogram of myosin showed an abnormality in the light chain pattern which could not be explained by a disproportion of normal fiber types.", "contents": "Characteristics of myosin in nemaline myopathy. Electron-microscopic, morphometric, histochemical and biochemical studies were carried out on muscle biopsies from a patient with the characteristic clinical and pathological findings of nemaline myopathy. The mean fiber diameter was decreased, and the vastus lateralis muscle biopsy consisted exclusively of slow twitch (Type I) fibers. Quantitative biochemical investigations revealed significantly low calcium uptake and ATPase activity of the fragmented sarcoplasmic reticulum and decreased myosin ATPase activity. The electrophoretogram of myosin showed an abnormality in the light chain pattern which could not be explained by a disproportion of normal fiber types."} {"id": "PMID:175136", "title": "The effects of dbcAMP on adreanl chromaffin cells in organotypic culture.", "content": "Chromaffin cells in organotypic cultures of adrenal glands from 19 day rat embryos developed a marked increase in the volume of their rough endoplasmic reticulum (RER) and enlargement of nucleoli in response to 1 mM dibutyryl cyclic AMP (dbcAMP) treatment for 17 days in vitro. 0.1 mM dbcAMP had a similar but less dramatic effect. When dbcAMP was removed from the medium after 11 days in vitro, cells became more like control explants treated with no additives, suggesting the effects of dbcAMP were reversible. ACTH which selectively stimulates adrenal cortical cells had no effect on RER morphology of chromaffin cells. The 'neuronal-like' configuration of dbcAMP treated chromaffin cells is discussed.", "contents": "The effects of dbcAMP on adreanl chromaffin cells in organotypic culture. Chromaffin cells in organotypic cultures of adrenal glands from 19 day rat embryos developed a marked increase in the volume of their rough endoplasmic reticulum (RER) and enlargement of nucleoli in response to 1 mM dibutyryl cyclic AMP (dbcAMP) treatment for 17 days in vitro. 0.1 mM dbcAMP had a similar but less dramatic effect. When dbcAMP was removed from the medium after 11 days in vitro, cells became more like control explants treated with no additives, suggesting the effects of dbcAMP were reversible. ACTH which selectively stimulates adrenal cortical cells had no effect on RER morphology of chromaffin cells. The 'neuronal-like' configuration of dbcAMP treated chromaffin cells is discussed."} {"id": "PMID:175137", "title": "Ventral horn synaptology in the rat.", "content": "The synaptology of the normal ventral horn of the rat was studied. Presynaptic boutons were classified as S (Spherical vesicles), F (flattened vesicles), and G (predominance of 700-1200 A granular vesicles). In addition, Cf, Cs, M, and T synaptic complexes were defined and quantitated. Synaptology was studied on alpha-motoneuron somata, alpha-motoneuron primary dendrites, peripheral dendrites and interneuron somata. In addition, organelles were quantified for the pre- and postsynaptic members of the synaptic complex. All counts were made on coded material and these data were analyzed statistically. Motoneuron somata had significantly more (P less than 0.01) F (58%) than S (33%) boutons. This was also the case for the motoneuron primary dendrite (P less than 0.01; F, 61%; S, 37%). The small dendrites had more (P less than 0.05) S (56%) than F (44%) boutons. More Cf bulbs (P less than 0.01) were found on motoneuron somata (9%) than on motoneuron primary dendrites (2%) or interneruon somata (3%). The C complex presynaptic bouton contained spherical (Cs) or flattened (Cf) synaptic vesicles which were attributed to the fixation employed. Cf bulbs were not observed on small dendrites. G bulbs were observed (less than 1%) only on small dendrites M bulbs were not observed on any postsynaptic structure. The boutons of the motoneuron primary dendrites (15% of total afferents) and peripheral dendrites (14% of total afferents) were frequently branched whereas there was significantly (P less than 0.01) less branching of boutons on motoneuron and interneuron somata. Small postsynaptic subsurface cisterns were associated with boutons of both the S and F type on all structures. In addition, these cisterns were observed in motoneuron somata (4%) and interneuron somata (2%) without an accompanying bouton. C postsynaptic organelles were observed in motoneuron somata (3%) and primary dendrites (1%) with an overlying neuroglial cell process and no presynaptic bouton. The synaptology of the rat ventral horn is comparable to that in the cat and monkey. However, M (R) and P bulbs were not observed in the rat. This could be due to the sampling method which indicated that synapses with less than 1% occurrence fall at the level of statistical resolution in quantitative electron microscopy. The presence of postsynaptic specialization usually associated with presynaptic boutons with no presynaptic component may be a reflection of the dynamics of normal bouton renewal in the rat ventral horn.", "contents": "Ventral horn synaptology in the rat. The synaptology of the normal ventral horn of the rat was studied. Presynaptic boutons were classified as S (Spherical vesicles), F (flattened vesicles), and G (predominance of 700-1200 A granular vesicles). In addition, Cf, Cs, M, and T synaptic complexes were defined and quantitated. Synaptology was studied on alpha-motoneuron somata, alpha-motoneuron primary dendrites, peripheral dendrites and interneuron somata. In addition, organelles were quantified for the pre- and postsynaptic members of the synaptic complex. All counts were made on coded material and these data were analyzed statistically. Motoneuron somata had significantly more (P less than 0.01) F (58%) than S (33%) boutons. This was also the case for the motoneuron primary dendrite (P less than 0.01; F, 61%; S, 37%). The small dendrites had more (P less than 0.05) S (56%) than F (44%) boutons. More Cf bulbs (P less than 0.01) were found on motoneuron somata (9%) than on motoneuron primary dendrites (2%) or interneruon somata (3%). The C complex presynaptic bouton contained spherical (Cs) or flattened (Cf) synaptic vesicles which were attributed to the fixation employed. Cf bulbs were not observed on small dendrites. G bulbs were observed (less than 1%) only on small dendrites M bulbs were not observed on any postsynaptic structure. The boutons of the motoneuron primary dendrites (15% of total afferents) and peripheral dendrites (14% of total afferents) were frequently branched whereas there was significantly (P less than 0.01) less branching of boutons on motoneuron and interneuron somata. Small postsynaptic subsurface cisterns were associated with boutons of both the S and F type on all structures. In addition, these cisterns were observed in motoneuron somata (4%) and interneuron somata (2%) without an accompanying bouton. C postsynaptic organelles were observed in motoneuron somata (3%) and primary dendrites (1%) with an overlying neuroglial cell process and no presynaptic bouton. The synaptology of the rat ventral horn is comparable to that in the cat and monkey. However, M (R) and P bulbs were not observed in the rat. This could be due to the sampling method which indicated that synapses with less than 1% occurrence fall at the level of statistical resolution in quantitative electron microscopy. The presence of postsynaptic specialization usually associated with presynaptic boutons with no presynaptic component may be a reflection of the dynamics of normal bouton renewal in the rat ventral horn."} {"id": "PMID:175138", "title": "Chemistry of 99mTc tracers. II. In vitro conversion of tagged HEDP and pyrophosphate (bone-seekers) into gluconate (renal agent). Effects of Ca and Fe (ii) on in vivo distribution.", "content": "Sodium gluconate transforms the bone-seekers 99mTc-HEDP and 99mTc-pyrophosphate into the renal agent 99mTc-gluconate. In these in vitro processes, pyrophosphate is displaced faster than HEDP, while the HEDP reaction is accelerated by calcium ions. The in vivo distributions of these bone and kidney agents are altered by the prior local injection of calcium or iron(II). These transformation and translocation phenomena are explained in terms of the mechanistic behavior of Tc(IV) complexes.", "contents": "Chemistry of 99mTc tracers. II. In vitro conversion of tagged HEDP and pyrophosphate (bone-seekers) into gluconate (renal agent). Effects of Ca and Fe (ii) on in vivo distribution. Sodium gluconate transforms the bone-seekers 99mTc-HEDP and 99mTc-pyrophosphate into the renal agent 99mTc-gluconate. In these in vitro processes, pyrophosphate is displaced faster than HEDP, while the HEDP reaction is accelerated by calcium ions. The in vivo distributions of these bone and kidney agents are altered by the prior local injection of calcium or iron(II). These transformation and translocation phenomena are explained in terms of the mechanistic behavior of Tc(IV) complexes."} {"id": "PMID:175140", "title": "Studies on myoinositol. Effects of caffeine and theophylline on incorporation of myoinositol into phosphatidylinositol in rat liver homogenate.", "content": "Both caffeine and theophylline, which were known to be potent inhibitors of cyclic-AMP phosphodiesterase, stimulated the incorporation of myoinositol into phosphatidylinositol in rat liver homogenate. However, cyclic-AMP had no effect. The effect of dibutyryl-cyclic-AMP differed with different concentrations. These results suggest that the stimulation cannot be explained by the increase in the amount of cyclic-AMP. This view was supported by the fact that papaverine, cyclic-AMP phosphodiesterase inhibitor, did not stimulate the incorporation and imidazole, the phosphodiesterase stimulator, did not inhibit the incorporation, and that adenylcyclase stimulators, epinephrine and glucagon, did not stimulate the incorporation.", "contents": "Studies on myoinositol. Effects of caffeine and theophylline on incorporation of myoinositol into phosphatidylinositol in rat liver homogenate. Both caffeine and theophylline, which were known to be potent inhibitors of cyclic-AMP phosphodiesterase, stimulated the incorporation of myoinositol into phosphatidylinositol in rat liver homogenate. However, cyclic-AMP had no effect. The effect of dibutyryl-cyclic-AMP differed with different concentrations. These results suggest that the stimulation cannot be explained by the increase in the amount of cyclic-AMP. This view was supported by the fact that papaverine, cyclic-AMP phosphodiesterase inhibitor, did not stimulate the incorporation and imidazole, the phosphodiesterase stimulator, did not inhibit the incorporation, and that adenylcyclase stimulators, epinephrine and glucagon, did not stimulate the incorporation."} {"id": "PMID:175141", "title": "Collagenase studies in bones of guinea pigs.", "content": "A specific collagenase has been demonstrated in culture fluids of guinea pig bones. Based on the acrylamide gel electrophoretic pattern, the mechanism of action of guinea pig bone collagenase appears similar to other known vertebrate collagenases. 2 peaks of enzymatic activity were found upon assay of fractions from gel chromatography, corresponding to molecular weights in the range of 137,000 daltons and 29,000 daltons. The enzyme is inhibited by cysteine and EDTA. Alpha1-macroglobulin is a much stronger inhibitor of the collagenase than alpha-antitrypsin. Activation studies suggested the presence of a proenzyme to guinea pig bone collagenase that was converted to an active enzyme by proteases present in the culture fluid.", "contents": "Collagenase studies in bones of guinea pigs. A specific collagenase has been demonstrated in culture fluids of guinea pig bones. Based on the acrylamide gel electrophoretic pattern, the mechanism of action of guinea pig bone collagenase appears similar to other known vertebrate collagenases. 2 peaks of enzymatic activity were found upon assay of fractions from gel chromatography, corresponding to molecular weights in the range of 137,000 daltons and 29,000 daltons. The enzyme is inhibited by cysteine and EDTA. Alpha1-macroglobulin is a much stronger inhibitor of the collagenase than alpha-antitrypsin. Activation studies suggested the presence of a proenzyme to guinea pig bone collagenase that was converted to an active enzyme by proteases present in the culture fluid."} {"id": "PMID:175142", "title": "Atypical hidradenoma arising in a dermoid cyst of the spinal canal.", "content": "A spinal dermoid cyst with an invasive sweat-gland tumour in its wall is reported. This appears to be the first of this type to be reported in the nervous system.", "contents": "Atypical hidradenoma arising in a dermoid cyst of the spinal canal. A spinal dermoid cyst with an invasive sweat-gland tumour in its wall is reported. This appears to be the first of this type to be reported in the nervous system."} {"id": "PMID:175143", "title": "Chronic cytomegalovirus infection, immunodeficiency, and monoclonal gammopathy-antigen-driven malignancy?", "content": "An infant with severe combined immunodeficiency had normal numbers of lymphocytes which bore E rosette and surface Ig markers in an appropriate distribution. However, only minimal responsivity to in vitro stimulation by mitogens and allogenic cells, and none to antigens could be elicited; functional antibody responses were also nil, except to cytomegalovirus. Intrauterine-acquired cytomegalovirus may have caused his immune dysfunction, although the possibility of a postnatal infection cannot be excluded. Therapy with transfer factor and thymus transplantation was unsucessful in restoring immunity and may have aggravated a pre-existing monoclonal gammopathy. It is possible that the monoclonal protein was derived from B-cells transplacentally received from the patients mother.", "contents": "Chronic cytomegalovirus infection, immunodeficiency, and monoclonal gammopathy-antigen-driven malignancy? An infant with severe combined immunodeficiency had normal numbers of lymphocytes which bore E rosette and surface Ig markers in an appropriate distribution. However, only minimal responsivity to in vitro stimulation by mitogens and allogenic cells, and none to antigens could be elicited; functional antibody responses were also nil, except to cytomegalovirus. Intrauterine-acquired cytomegalovirus may have caused his immune dysfunction, although the possibility of a postnatal infection cannot be excluded. Therapy with transfer factor and thymus transplantation was unsucessful in restoring immunity and may have aggravated a pre-existing monoclonal gammopathy. It is possible that the monoclonal protein was derived from B-cells transplacentally received from the patients mother."} {"id": "PMID:175144", "title": "Parathyroid function tests with EDTA infusions in infancy and childhood.", "content": "To determine the functional capabilities of the parathyroid glands, 17 EDTA infusions were given to 11 children (ages 1 month to 12 years) and to two mothers of four of the children. Serum ionized Ca fell from 4.1 mg/dl to 3.4 mg/dl. Excessive parathyroid hormone responses were elicited during seven of nine EDTA infusions in five children and in one adult with hypophosphatemic rickets, during the active phase of rickets. In four of five subjects with problems related to hypercalcemia, borderline low or undetectable PTH responses were elicited. Three relatively normal PTH responses were obtained, two in an infant after phosphate-induced hypocalcemic tetany was corrected, and one in a child with a malabsorption syndrome. The renal tubular reabsorption of phosphate was inversely related and the urinary cyclic AMP excretion was positively related to the PTH response. Thus EDTA infusions in infants and children might be useful in the identification of hyper-, normo-, or hypoparathyroid states and would be of value in defining the functional condition of the parathyroid glands in children with deranged Ca or P metabolism.", "contents": "Parathyroid function tests with EDTA infusions in infancy and childhood. To determine the functional capabilities of the parathyroid glands, 17 EDTA infusions were given to 11 children (ages 1 month to 12 years) and to two mothers of four of the children. Serum ionized Ca fell from 4.1 mg/dl to 3.4 mg/dl. Excessive parathyroid hormone responses were elicited during seven of nine EDTA infusions in five children and in one adult with hypophosphatemic rickets, during the active phase of rickets. In four of five subjects with problems related to hypercalcemia, borderline low or undetectable PTH responses were elicited. Three relatively normal PTH responses were obtained, two in an infant after phosphate-induced hypocalcemic tetany was corrected, and one in a child with a malabsorption syndrome. The renal tubular reabsorption of phosphate was inversely related and the urinary cyclic AMP excretion was positively related to the PTH response. Thus EDTA infusions in infants and children might be useful in the identification of hyper-, normo-, or hypoparathyroid states and would be of value in defining the functional condition of the parathyroid glands in children with deranged Ca or P metabolism."} {"id": "PMID:175146", "title": "Eye movements during REM sleep: the influence of personality and presleep conditions.", "content": "Male subjects scoring high (n=17) or low (n=14) on the Maudsley Neuroticism scale were randomly assigned to a positive (n=17) or negative (ego threat) (n=14) presleep condition and then slept a single night in the laboratory. The negative condition elicited significantly more rapid eye movement activity (REM density) than did the positive condition (pless than.03). There was a significant interaction for Groups X Conditions (pless than.007) indicating that low neuroticism subjects had greater REM density in the negative condition, and less REM density in the positive condition, compared to high neuroticism subjects under either condition. The low neuroticism subjects in the negative condition showed a discrepancy between greater REM density but less admission of stress on a presleep mood questionnaire compared to high neuroticism subjects. These results support the hypothesis that REM density is a correlate of stress-induced arousal that is subject to the modifying effects of individual differences.", "contents": "Eye movements during REM sleep: the influence of personality and presleep conditions. Male subjects scoring high (n=17) or low (n=14) on the Maudsley Neuroticism scale were randomly assigned to a positive (n=17) or negative (ego threat) (n=14) presleep condition and then slept a single night in the laboratory. The negative condition elicited significantly more rapid eye movement activity (REM density) than did the positive condition (pless than.03). There was a significant interaction for Groups X Conditions (pless than.007) indicating that low neuroticism subjects had greater REM density in the negative condition, and less REM density in the positive condition, compared to high neuroticism subjects under either condition. The low neuroticism subjects in the negative condition showed a discrepancy between greater REM density but less admission of stress on a presleep mood questionnaire compared to high neuroticism subjects. These results support the hypothesis that REM density is a correlate of stress-induced arousal that is subject to the modifying effects of individual differences."} {"id": "PMID:175147", "title": "Effect of bradykinin on transepithelial transfer of sodium and water in vitro.", "content": "Mucosal sodium and water transfer were measured in everted sacs of rat jejunum. 2. Bradykinin (7.86 X 10(-12)M), when present in both mucosal and serosal solutions, produced a biphasic effect on mucosal sodium and water transfer. When basal transfer was low a stimulation was observed whereas an inhibition of transfer was observed when basal transfer was high. Bradykinin at concentrations of 7-86 X 10(-11) and 7-86 X 10(-13) M produced qualitatively similar effects. 3. Inhibition of transfer was observed whether bradykinin was present in the mucosal, serosal or both solutions. Stimulation of transfer was observed only when bradykinin was present in the serosal solution. 4. Theophylline (1 mM), alone inhibited water transfer at high and intermediate levels of basal transfer, and significantly potentiated the inhibitory effect of bradykinin (7-86 X 10(-12)M) on water transfer at intermediate levels of control transfer. 5. Cyclic AMP (1 mM) inhibited water transfer when basal transfer was high. Dibutyryl cyclic AMP (1 mM) inhibited water transfer at all levels of basal transfer. Dibutyryl cyclic AMP (1 mM) and bradykinin (7-86 X 10(-12)M) together produced a significantly greater inhibition of water transfer than either agent alone, at intermediate basal transfer. 6. It was observed that the action of bradykinin upon sodium and water transfer consists of two different and opposing effects. It is possible that the inhibitory effect of bradykinin upon water transfer is related to increased cyclic AMP activity.", "contents": "Effect of bradykinin on transepithelial transfer of sodium and water in vitro. Mucosal sodium and water transfer were measured in everted sacs of rat jejunum. 2. Bradykinin (7.86 X 10(-12)M), when present in both mucosal and serosal solutions, produced a biphasic effect on mucosal sodium and water transfer. When basal transfer was low a stimulation was observed whereas an inhibition of transfer was observed when basal transfer was high. Bradykinin at concentrations of 7-86 X 10(-11) and 7-86 X 10(-13) M produced qualitatively similar effects. 3. Inhibition of transfer was observed whether bradykinin was present in the mucosal, serosal or both solutions. Stimulation of transfer was observed only when bradykinin was present in the serosal solution. 4. Theophylline (1 mM), alone inhibited water transfer at high and intermediate levels of basal transfer, and significantly potentiated the inhibitory effect of bradykinin (7-86 X 10(-12)M) on water transfer at intermediate levels of control transfer. 5. Cyclic AMP (1 mM) inhibited water transfer when basal transfer was high. Dibutyryl cyclic AMP (1 mM) inhibited water transfer at all levels of basal transfer. Dibutyryl cyclic AMP (1 mM) and bradykinin (7-86 X 10(-12)M) together produced a significantly greater inhibition of water transfer than either agent alone, at intermediate basal transfer. 6. It was observed that the action of bradykinin upon sodium and water transfer consists of two different and opposing effects. It is possible that the inhibitory effect of bradykinin upon water transfer is related to increased cyclic AMP activity."} {"id": "PMID:175148", "title": "Effects of divalent cations and of catecholamines on the late response of the superior cervical ganglion.", "content": "The characteristics of the late response of the superior cervical ganglion of dogs were studied by close-arterial injection of catecholamines and divalent cations to the ganglion. 2. Dopamine, noradrenaline and adrenaline inhibit the late response as well as ganglionic activity induced by other means. The effect of dopamine is brief but that of adrenaline is prolonged. 3. Cd2+, Co2+, Ni2+, Zn2+, Hg2+ and Fe2+ markedly potentiate the late response, whereas Mn2+, Ca2+ and Mg2+ inhibit it. 4. may potentiate ganglionic activity triggered by other ganglionic stimulants. The Cd-augmented activity may be blocked by a ganglion-blocker which is specific to the stimulant. 5. CdCl2 may exhibit a direct ganglion-stimulating action on a ganglion which shows prominent late responses and has been conditioned by tetanic preganglionic stimulation. 6. CdCl2 and MnCl2 may inhibit ganglionic transmission by suppressing acetylcholine release from presynaptic nerve terminals. 7. It is concluded that the late response represents the late discharges of ganglion cells, which are very sensitive to inhibition by CaCl2 and MnCl2 and may be potentiated by CdCl2.", "contents": "Effects of divalent cations and of catecholamines on the late response of the superior cervical ganglion. The characteristics of the late response of the superior cervical ganglion of dogs were studied by close-arterial injection of catecholamines and divalent cations to the ganglion. 2. Dopamine, noradrenaline and adrenaline inhibit the late response as well as ganglionic activity induced by other means. The effect of dopamine is brief but that of adrenaline is prolonged. 3. Cd2+, Co2+, Ni2+, Zn2+, Hg2+ and Fe2+ markedly potentiate the late response, whereas Mn2+, Ca2+ and Mg2+ inhibit it. 4. may potentiate ganglionic activity triggered by other ganglionic stimulants. The Cd-augmented activity may be blocked by a ganglion-blocker which is specific to the stimulant. 5. CdCl2 may exhibit a direct ganglion-stimulating action on a ganglion which shows prominent late responses and has been conditioned by tetanic preganglionic stimulation. 6. CdCl2 and MnCl2 may inhibit ganglionic transmission by suppressing acetylcholine release from presynaptic nerve terminals. 7. It is concluded that the late response represents the late discharges of ganglion cells, which are very sensitive to inhibition by CaCl2 and MnCl2 and may be potentiated by CdCl2."} {"id": "PMID:175150", "title": "Effects of physiologic alterations on binomial transmitter release at magnesium-depressed neuromuscular junctions.", "content": "1. Transmitter release from Mg2+-treated frog neuromuscular junctions can be described by binomial statistics. Good agreement between the observed amplitude-frequency distribution of e.p.p.s. and that predicted by binomial statistics is observed with relatively low concentrations of Mg2+. Conversely, good agreement is found with Poisson predictions when higher concentrations of Mg2+ are used to depress transmission. 2. Binomial analysis at these junctions shows that Mg2+ reduces quantal content (m), the probability of release (p) and to a lesser extent the available stores of transmitter (n). Raising Ca2+ causes an increase in n and p and a small but significant increase in n. K+ increases m and p but not n. 3. During 'frequency-facilitation' (1-6 Hz), e.p.p.s., m and n are increased but p is unaffected. 4. It is concluded that binomial statistics can be used to estimate the quantal parameters of transmitter release and that these parameters can be identified as discrete entities.", "contents": "Effects of physiologic alterations on binomial transmitter release at magnesium-depressed neuromuscular junctions. 1. Transmitter release from Mg2+-treated frog neuromuscular junctions can be described by binomial statistics. Good agreement between the observed amplitude-frequency distribution of e.p.p.s. and that predicted by binomial statistics is observed with relatively low concentrations of Mg2+. Conversely, good agreement is found with Poisson predictions when higher concentrations of Mg2+ are used to depress transmission. 2. Binomial analysis at these junctions shows that Mg2+ reduces quantal content (m), the probability of release (p) and to a lesser extent the available stores of transmitter (n). Raising Ca2+ causes an increase in n and p and a small but significant increase in n. K+ increases m and p but not n. 3. During 'frequency-facilitation' (1-6 Hz), e.p.p.s., m and n are increased but p is unaffected. 4. It is concluded that binomial statistics can be used to estimate the quantal parameters of transmitter release and that these parameters can be identified as discrete entities."} {"id": "PMID:175154", "title": "An electrophysiological study of chemical and electrical synapses on neurones in the parasympathetic cardiac ganglion of the mudpuppy, Necturus maculosus: evidence for intrinsic ganglionic innervation.", "content": "1. The cardiac ganglion of the mudpuppy is situated on a thin sheet of tissue. Two nerve cell types can be distinguished readily in the living preparation - principal cells and smaller interneurones which synapse with the principal cells. The purpose of this study was to investigate synaptic transmission and the functional organization of neuronal connections of ganglion cells with intracellular micro-electrodes. 2. Stimulation of the preganglionic, vagus, nerves evoked a large excitatory response in principal cells. About three quarters of these neurones were innervated by a single vagal axon. The remaining cells received two or more preganglionic nerve fibres. 3. The quantum content of vagal excitatory post-synaptic potentials (e.p.s.p.s) was measured. Normally, the e.p.s.p. was suprathreshold and consisted of about twenty-two quanta, whereas only about nine quanta were required to reach threshold and initiate an action potential. 4. Intracellular stimulation of principal cells evoked e.p.s.p.s in neighbouring principal cells. The responses were blocked by cholinergic antagonists. These potentials were caused by excitation of principal cell axon collateral synapses. 5. Principal cells also formed electrical junctions with each other. These electrical junctions were very weak. Although they transmitted slow potential changes, only a small response was recorded in one cell when an electrically coupled neighbouring cell fired an impulse. The resistance of the electrical junction between principal cells was calculated to be about 5-8 X 10(8) omega. 6. Stable penetrations of interneurones were only rarely achieved, making it difficult to study their functional relationship to principal cells. Action potentials were recorded from interneurones in a few instances. 7. These data demonstrate that parasympathetic ganglion cells in the heart of the mudpuppy receive innervation from more than one source involving both chemical and electrical synapses, and that some of the synapses are intrinsic to the ganglion.", "contents": "An electrophysiological study of chemical and electrical synapses on neurones in the parasympathetic cardiac ganglion of the mudpuppy, Necturus maculosus: evidence for intrinsic ganglionic innervation. 1. The cardiac ganglion of the mudpuppy is situated on a thin sheet of tissue. Two nerve cell types can be distinguished readily in the living preparation - principal cells and smaller interneurones which synapse with the principal cells. The purpose of this study was to investigate synaptic transmission and the functional organization of neuronal connections of ganglion cells with intracellular micro-electrodes. 2. Stimulation of the preganglionic, vagus, nerves evoked a large excitatory response in principal cells. About three quarters of these neurones were innervated by a single vagal axon. The remaining cells received two or more preganglionic nerve fibres. 3. The quantum content of vagal excitatory post-synaptic potentials (e.p.s.p.s) was measured. Normally, the e.p.s.p. was suprathreshold and consisted of about twenty-two quanta, whereas only about nine quanta were required to reach threshold and initiate an action potential. 4. Intracellular stimulation of principal cells evoked e.p.s.p.s in neighbouring principal cells. The responses were blocked by cholinergic antagonists. These potentials were caused by excitation of principal cell axon collateral synapses. 5. Principal cells also formed electrical junctions with each other. These electrical junctions were very weak. Although they transmitted slow potential changes, only a small response was recorded in one cell when an electrically coupled neighbouring cell fired an impulse. The resistance of the electrical junction between principal cells was calculated to be about 5-8 X 10(8) omega. 6. Stable penetrations of interneurones were only rarely achieved, making it difficult to study their functional relationship to principal cells. Action potentials were recorded from interneurones in a few instances. 7. These data demonstrate that parasympathetic ganglion cells in the heart of the mudpuppy receive innervation from more than one source involving both chemical and electrical synapses, and that some of the synapses are intrinsic to the ganglion."} {"id": "PMID:175155", "title": "The acetylcholine sensitivity of the surface membrane of multiply-innervated parasympathetic ganglion cells in the mudpuppy before and after partial denervation.", "content": "1. The surface chemosensitivity to iontophoretically applied acetylcholine (ACh) of single nerve cells in the cardiac ganglion of the mudpuppy was examined. 2. Some synapses on the neurones can be recognized in the living preparation with differential interference contrast optics. Identified synaptic regions of the ganglion cells were more sensitive to ACh than were other areas. The mean sensitivity of synaptic areas was 509 mV/nC, but that of random spots on the cell surface (which were mainly non-synaptic) was only 190 mV/nC. The mean rise time of ACh responses at synapses was 23 msec and at random spots was 36 msec. These data suggest that the density of ACh receptors is highest under the synapses on the post-synaptic membrane. 3. When some, but not all, of the presynaptic terminals on the ganglion cells are destroyed by cutting the vagus nerve, the sensitivity of the entire surface membrane to applied ACh increases. This increase in sensitivity reaches a maximum about 4-6 weeks after the operation. 4. Synaptic transmission at excitatory collateral synapses which remain after vagal degeneration is not altered by this hypersensitivity. 5. Neurones from ganglia which have been isolated and maintained in organ culture also become hypersensitive to applied ACh. this heightened chemosensitivity deveoops much faster in vitro; hypersensitivity in cultured ganglia becomes manifest within 4-5 days, in contrast with 4-6 weeks after vagus degeneration in vivo.", "contents": "The acetylcholine sensitivity of the surface membrane of multiply-innervated parasympathetic ganglion cells in the mudpuppy before and after partial denervation. 1. The surface chemosensitivity to iontophoretically applied acetylcholine (ACh) of single nerve cells in the cardiac ganglion of the mudpuppy was examined. 2. Some synapses on the neurones can be recognized in the living preparation with differential interference contrast optics. Identified synaptic regions of the ganglion cells were more sensitive to ACh than were other areas. The mean sensitivity of synaptic areas was 509 mV/nC, but that of random spots on the cell surface (which were mainly non-synaptic) was only 190 mV/nC. The mean rise time of ACh responses at synapses was 23 msec and at random spots was 36 msec. These data suggest that the density of ACh receptors is highest under the synapses on the post-synaptic membrane. 3. When some, but not all, of the presynaptic terminals on the ganglion cells are destroyed by cutting the vagus nerve, the sensitivity of the entire surface membrane to applied ACh increases. This increase in sensitivity reaches a maximum about 4-6 weeks after the operation. 4. Synaptic transmission at excitatory collateral synapses which remain after vagal degeneration is not altered by this hypersensitivity. 5. Neurones from ganglia which have been isolated and maintained in organ culture also become hypersensitive to applied ACh. this heightened chemosensitivity deveoops much faster in vitro; hypersensitivity in cultured ganglia becomes manifest within 4-5 days, in contrast with 4-6 weeks after vagus degeneration in vivo."} {"id": "PMID:175158", "title": "How to be a helping person.", "content": "This paper is an attempt to summarize the essential ingredients of helping someone in need. The main element needed is the helpers interest in the person, be he student, employee, Army draftee, or patient. Eleven points of interviewing are outlined along with possible uses in training situations.", "contents": "How to be a helping person. This paper is an attempt to summarize the essential ingredients of helping someone in need. The main element needed is the helpers interest in the person, be he student, employee, Army draftee, or patient. Eleven points of interviewing are outlined along with possible uses in training situations."} {"id": "PMID:175162", "title": "Membranes of Tetrahymena. IV. Isolation and characterization of temperature-responsive smooth and rough microsomal subfractions.", "content": "Temperature-responsive microsomes of the ciliate protozoan Tetrahymena have been originally fractionated by step centrifugation on two-layered, Mg2+-containing sucrose gradients. Three fractions have been obtained, which are termed smooth I, smooth II and rough according to the appearance of the membrane vesicles upon electron-microscopy. Smooth I, smooth II, and rough microsomes exhibit RNA/protein ratios of 0.09, 0.20, and 0.34; their phospholipid/protein ratios and their neutral lipid/phospholipid ratios were 0.52, 0.43 and 0.25, and 0.17, 0.18 and 0.13, respectively. All three fractions contain equivalent, low succinic dehydrogenase and 5'-nucleotidase activities. Glucose-6-phosphatase and acid phosphatase are more concentrated in smooth I membranes than in rough membranes. The reverse is true for ATPase. The smooth II membranes occupy an intermediate position except that their ATPase activity is the lowest of the three fractions. The specific activities of these enzymes of the three microsomal fractions are compared to those of homogenates of whole cells. Thin-layer chromatography reveals a very similar polar and nonpolar lipid pattern of the three microsomal fractions. The major phospholipid compounds are phosphatidlethanolamine, glycerideaminoethylphosphonate and phosphatidylcholine, while diglycerides, an unknown NL-compound, and triglycerides are the major apolar lipids. Gas liquid chromatography shows that the fatty acids are mainly even-numbered ranging between C12 and C18. The smooth I, smooth II and rough membranes contain 65.2, 69.3 and 72.7% unsaturated fatty acids in their polar lipids, whereas only 52.7, 49.7 and 48.3% unsaturated acids are found in their apolar lipids, respectively. The fatty acids are more unevenly distributed among the individual polar lipids than in the apolar ones.", "contents": "Membranes of Tetrahymena. IV. Isolation and characterization of temperature-responsive smooth and rough microsomal subfractions. Temperature-responsive microsomes of the ciliate protozoan Tetrahymena have been originally fractionated by step centrifugation on two-layered, Mg2+-containing sucrose gradients. Three fractions have been obtained, which are termed smooth I, smooth II and rough according to the appearance of the membrane vesicles upon electron-microscopy. Smooth I, smooth II, and rough microsomes exhibit RNA/protein ratios of 0.09, 0.20, and 0.34; their phospholipid/protein ratios and their neutral lipid/phospholipid ratios were 0.52, 0.43 and 0.25, and 0.17, 0.18 and 0.13, respectively. All three fractions contain equivalent, low succinic dehydrogenase and 5'-nucleotidase activities. Glucose-6-phosphatase and acid phosphatase are more concentrated in smooth I membranes than in rough membranes. The reverse is true for ATPase. The smooth II membranes occupy an intermediate position except that their ATPase activity is the lowest of the three fractions. The specific activities of these enzymes of the three microsomal fractions are compared to those of homogenates of whole cells. Thin-layer chromatography reveals a very similar polar and nonpolar lipid pattern of the three microsomal fractions. The major phospholipid compounds are phosphatidlethanolamine, glycerideaminoethylphosphonate and phosphatidylcholine, while diglycerides, an unknown NL-compound, and triglycerides are the major apolar lipids. Gas liquid chromatography shows that the fatty acids are mainly even-numbered ranging between C12 and C18. The smooth I, smooth II and rough membranes contain 65.2, 69.3 and 72.7% unsaturated fatty acids in their polar lipids, whereas only 52.7, 49.7 and 48.3% unsaturated acids are found in their apolar lipids, respectively. The fatty acids are more unevenly distributed among the individual polar lipids than in the apolar ones."} {"id": "PMID:175163", "title": "Measure of enzymatic activity coincident with 2450 MHz microwave exposure.", "content": "Enzyme preparations were exposed to microwave radiation at 2450 MHz and enzymatic activity was simultaneously monitored spectrophotometrically with a crossed-beam exposure detection system. Enzymes studied were glucose 6-phosphate dehydrogenase from human red blood cells and yeast, adenylate kinase from rat liver mitochondria and rabbit muscle, and rat liver microsomal NADPH cytochrome c reductase. No difference was found between the specific activity at 25 degrees C of unirradiated controls and enzyme preparations irradiated at an absorbed dose rate of 42 W/kg.", "contents": "Measure of enzymatic activity coincident with 2450 MHz microwave exposure. Enzyme preparations were exposed to microwave radiation at 2450 MHz and enzymatic activity was simultaneously monitored spectrophotometrically with a crossed-beam exposure detection system. Enzymes studied were glucose 6-phosphate dehydrogenase from human red blood cells and yeast, adenylate kinase from rat liver mitochondria and rabbit muscle, and rat liver microsomal NADPH cytochrome c reductase. No difference was found between the specific activity at 25 degrees C of unirradiated controls and enzyme preparations irradiated at an absorbed dose rate of 42 W/kg."} {"id": "PMID:175174", "title": "A review of adenoviruses in the etiology of acute hemorrhagic cystitis.", "content": "In a comparison of children with acute hemorrhagic cystitis it was noted that 51 per cent of those in Sendai, Japan and 23 per cent of those in Chicago, Illinois had adenoviruria during their illness. These 2 populations are the only ones in which the disease has been studied and reported. In both populations male outnumbered female patients, with a ratio of 3.4 to 1 in Japanese children and 2.3 to 1 in American children. Adenovirus type 11 was isolated exclusively in both studies, with the exception of 2 American children who had adenovirus type 21 in the urine. While the Japanese children experienced their illnesses for approximately 2 weeks American children had symptoms for only 4 to 5 days. Virus shedding continued throughout the illness in both populations. The adenovirus 11 strains from American children were antigenically similar to the prototype adenovirus type 11 strain as measured by cross hemagglutination-inhibition procedures. Adenovirus antigen was identified by immunofluorescence in exfoliated bladder epithelial cells from patients with acute hemorrhagic cystitis. Studies to date indicate that adenovirus type 11 is the etiologic agent in some but not all pediatric cases of acute hemorrhagic cystitis.", "contents": "A review of adenoviruses in the etiology of acute hemorrhagic cystitis. In a comparison of children with acute hemorrhagic cystitis it was noted that 51 per cent of those in Sendai, Japan and 23 per cent of those in Chicago, Illinois had adenoviruria during their illness. These 2 populations are the only ones in which the disease has been studied and reported. In both populations male outnumbered female patients, with a ratio of 3.4 to 1 in Japanese children and 2.3 to 1 in American children. Adenovirus type 11 was isolated exclusively in both studies, with the exception of 2 American children who had adenovirus type 21 in the urine. While the Japanese children experienced their illnesses for approximately 2 weeks American children had symptoms for only 4 to 5 days. Virus shedding continued throughout the illness in both populations. The adenovirus 11 strains from American children were antigenically similar to the prototype adenovirus type 11 strain as measured by cross hemagglutination-inhibition procedures. Adenovirus antigen was identified by immunofluorescence in exfoliated bladder epithelial cells from patients with acute hemorrhagic cystitis. Studies to date indicate that adenovirus type 11 is the etiologic agent in some but not all pediatric cases of acute hemorrhagic cystitis."} {"id": "PMID:175176", "title": "Vidarabine therapy for severe herpesvirus infections. An unusual syndrome of chronic varicella and transient immunologic deficiency.", "content": "Six patients with severe herpesvirus infections were successfully treated with vidarabine. One patient had a previously undescribed syndrome of chronic cutaneous varicella infection of eight months' duration, associated with transient but complete duppression of lymphocyte response to conconavalin A. Other diagnoses were severe varicella pneumonia, progressive cytomegalovirus pneumonia associated with acute lymphocytic leukemia, herpes simplex encephalitis, severe zoster associated with stage IV lymphoma, and disseminated herpes simplex in a patient receiving high doses of steroids. All patients showed cessation of new lesions or abrupt clinical improvement between days 2 and 4 after initiation of therapy, and all were cured of their clinical infection. Dramatic improvement in all of our patients and the minimal toxicity observed make vidarabine suitable for use in severe herpesvirus infections.", "contents": "Vidarabine therapy for severe herpesvirus infections. An unusual syndrome of chronic varicella and transient immunologic deficiency. Six patients with severe herpesvirus infections were successfully treated with vidarabine. One patient had a previously undescribed syndrome of chronic cutaneous varicella infection of eight months' duration, associated with transient but complete duppression of lymphocyte response to conconavalin A. Other diagnoses were severe varicella pneumonia, progressive cytomegalovirus pneumonia associated with acute lymphocytic leukemia, herpes simplex encephalitis, severe zoster associated with stage IV lymphoma, and disseminated herpes simplex in a patient receiving high doses of steroids. All patients showed cessation of new lesions or abrupt clinical improvement between days 2 and 4 after initiation of therapy, and all were cured of their clinical infection. Dramatic improvement in all of our patients and the minimal toxicity observed make vidarabine suitable for use in severe herpesvirus infections."} {"id": "PMID:175178", "title": "Hepatic changes in young women ingesting contraceptive steroids. Hepatic hemorrhage and primary hepatic tumors.", "content": "Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role.", "contents": "Hepatic changes in young women ingesting contraceptive steroids. Hepatic hemorrhage and primary hepatic tumors. Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role."} {"id": "PMID:175201", "title": "Clostridia in soil of the Antarctica.", "content": "From the soil in the area around the Syowa Station, the East Ongul Island, the Antarctica, a total of 193 strains of clostridia were isolated and identified. It was surprising that the soil samples taken from the places which were considered to be scarcely contaminated by human beings and animals contained many clostridia. One hundred and fifty-five strains were assigned to 11 species, including C. perfringens, C. bifermentans, C. sordellii, C. sporogenes, C. plagarum, C. paraperfringens, C. septicum, C. tertium, C. cadaveris, C. butyricum and C. felsineum, but 38 strains remained unidentified. C. perfringens, C. bifermentans and C. sordellii were isolated very frequently and C. sporogenes less frequently. All the strains of C. sordellii were nonpathogenic and had almost the same characteristics as those of C. bifermentans except for the attitude in the urease test. The peculiar distribution and characteristics of the clostridia in the Antarctic soil were discussed in comparison with those found in the soil in Japan.", "contents": "Clostridia in soil of the Antarctica. From the soil in the area around the Syowa Station, the East Ongul Island, the Antarctica, a total of 193 strains of clostridia were isolated and identified. It was surprising that the soil samples taken from the places which were considered to be scarcely contaminated by human beings and animals contained many clostridia. One hundred and fifty-five strains were assigned to 11 species, including C. perfringens, C. bifermentans, C. sordellii, C. sporogenes, C. plagarum, C. paraperfringens, C. septicum, C. tertium, C. cadaveris, C. butyricum and C. felsineum, but 38 strains remained unidentified. C. perfringens, C. bifermentans and C. sordellii were isolated very frequently and C. sporogenes less frequently. All the strains of C. sordellii were nonpathogenic and had almost the same characteristics as those of C. bifermentans except for the attitude in the urease test. The peculiar distribution and characteristics of the clostridia in the Antarctic soil were discussed in comparison with those found in the soil in Japan."} {"id": "PMID:175203", "title": "Monolayer cell culture of human pancreatic beta cell tumor: effect of glucose and somatostatin on insulin release.", "content": "A human pancreatic beta cell tumor was maintained in monolayer cell culture for 80 days. The culture was terminated because of bacterial infection. Probably because extensive trypsin-collagenase dissociation was unnecessary, the dissociated cells attached much more quickly to the surface of the culture flask than do rat pancreatic cells obtained by enzymatic dissociation. Insulin release not only oscillated widely during the first 40 days of culture but also showed a decline from 380 mU the first week to about 50 mU/week the seventh week. For some unknown reason fibroblast overgrowth was not a major problem. Reduction of the medium glucose concentration from 16.5 mM to 5.5 mM did not alter insulin release rate. At glucose concentration of 16.5 mM, somatostatin 1.0 mug/ml reduced insulin release by 40%. From our previously reported studies on the effect of somatostatin on insulin release by monolayer cell cultures of rat endocrine pancreas, we conclude that the constant release of insulin by the tumor cells is relatively nonstimulated. We have confirmed that monolayer cultures of human pancreatic beta cell tumor do not represent a good model for normal human beta cell function because of the major shortcoming of an apparent inability to recognize glucose as a secretogogue.", "contents": "Monolayer cell culture of human pancreatic beta cell tumor: effect of glucose and somatostatin on insulin release. A human pancreatic beta cell tumor was maintained in monolayer cell culture for 80 days. The culture was terminated because of bacterial infection. Probably because extensive trypsin-collagenase dissociation was unnecessary, the dissociated cells attached much more quickly to the surface of the culture flask than do rat pancreatic cells obtained by enzymatic dissociation. Insulin release not only oscillated widely during the first 40 days of culture but also showed a decline from 380 mU the first week to about 50 mU/week the seventh week. For some unknown reason fibroblast overgrowth was not a major problem. Reduction of the medium glucose concentration from 16.5 mM to 5.5 mM did not alter insulin release rate. At glucose concentration of 16.5 mM, somatostatin 1.0 mug/ml reduced insulin release by 40%. From our previously reported studies on the effect of somatostatin on insulin release by monolayer cell cultures of rat endocrine pancreas, we conclude that the constant release of insulin by the tumor cells is relatively nonstimulated. We have confirmed that monolayer cultures of human pancreatic beta cell tumor do not represent a good model for normal human beta cell function because of the major shortcoming of an apparent inability to recognize glucose as a secretogogue."} {"id": "PMID:175204", "title": "Dysuria in women.", "content": "Only 46% of 84 women with dysuria were found to have significant bacteriuria while 8% had gonorrhea, 1% had herpes progenitalis and 17% had monilia and Trichomonas vaginitis. The remainder were considered to have the urethral syndrome. Neither pyuria, microscopic bacteriuria, nor any single subjective or objective datum definitively predicted cystitis at the initial visit. Therefore, we advise formulating the problem as \"dysuria\" at the initial evaluation even though one treats with an antimicrobial. The initial workup should include a routine urinalysis, gram stain of the urinary sediment, urine culture, an examination of the urethra and labia as well as a urethral culture. Complete pelvic examination is useful in documenting gonorrhea, herpes progenitalis or vaginitis. If the pelvic examination is deferred and the initial urine culture is negative, reevaluation of the dysuria should include a pelvic examination.", "contents": "Dysuria in women. Only 46% of 84 women with dysuria were found to have significant bacteriuria while 8% had gonorrhea, 1% had herpes progenitalis and 17% had monilia and Trichomonas vaginitis. The remainder were considered to have the urethral syndrome. Neither pyuria, microscopic bacteriuria, nor any single subjective or objective datum definitively predicted cystitis at the initial visit. Therefore, we advise formulating the problem as \"dysuria\" at the initial evaluation even though one treats with an antimicrobial. The initial workup should include a routine urinalysis, gram stain of the urinary sediment, urine culture, an examination of the urethra and labia as well as a urethral culture. Complete pelvic examination is useful in documenting gonorrhea, herpes progenitalis or vaginitis. If the pelvic examination is deferred and the initial urine culture is negative, reevaluation of the dysuria should include a pelvic examination."} {"id": "PMID:175206", "title": "[Clinical features and pathology of Resochin - implantation in the cornea (author's transl)].", "content": "The long-term therapy with Resochin leads in a proportion of cases to reversible changes in the cornea. There is no direct relationship between the total dose used and the keratopathy. Point-like \"Infiltrations\" can be identified histologically in the cytoplasm of the epithelium and also vacuolised cells and cell necrosis, mainly in the surface epithelial layers. Under the electron microscope one can see, alongside intact cells, cells with multiple lyosomal inclusions, surrounded by a membrane, and myelin figures. The changes described are probably to be seen as after-effects of the influence of the drug.", "contents": "[Clinical features and pathology of Resochin - implantation in the cornea (author's transl)]. The long-term therapy with Resochin leads in a proportion of cases to reversible changes in the cornea. There is no direct relationship between the total dose used and the keratopathy. Point-like \"Infiltrations\" can be identified histologically in the cytoplasm of the epithelium and also vacuolised cells and cell necrosis, mainly in the surface epithelial layers. Under the electron microscope one can see, alongside intact cells, cells with multiple lyosomal inclusions, surrounded by a membrane, and myelin figures. The changes described are probably to be seen as after-effects of the influence of the drug."} {"id": "PMID:175208", "title": "[Influence of somatastatin on oral glucose tolerance in autonomous hypersecretion of growth hormone, prolactin or insulin (author's transl)].", "content": "Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.", "contents": "[Influence of somatastatin on oral glucose tolerance in autonomous hypersecretion of growth hormone, prolactin or insulin (author's transl)]. Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states."} {"id": "PMID:175210", "title": "[Diarrhea and islet cell tumor. Clinical and morphological report on 2 observations].", "content": "The combination of diarrhea with an islet cell tumor (Verner-Morrison Syndrome) is a clinical picture presenting many diagnostic problems. It is probable that larger numbers of cases will be encountered with more widespread knowledge of this disease. The clinical features and the pathologic-anatomical findings of two characteristic cases are reported and discussed.", "contents": "[Diarrhea and islet cell tumor. Clinical and morphological report on 2 observations]. The combination of diarrhea with an islet cell tumor (Verner-Morrison Syndrome) is a clinical picture presenting many diagnostic problems. It is probable that larger numbers of cases will be encountered with more widespread knowledge of this disease. The clinical features and the pathologic-anatomical findings of two characteristic cases are reported and discussed."} {"id": "PMID:175209", "title": "[The Verner-Morrison syndrome. The clinical picture and pathologic anatomy].", "content": "The Verner-Morrison Syndrome is a clinically defined entity caused by an islet cell tumor of the pancreas. More than 60 cases have been described so long. The syndrome is characterized by diarrhea, hypokalemia and hypochlorhydria. In addition to a diabetic disposition, raised calcium levels and skin alterations may be present. The diagnosis is a clinical one. A pancreatic tumor should be searched for and removed. Morphologically a benign and a maligne islet cell tumor or a diffuse hyperplasia of the islets of Langerhans can be found. Until now identification of the tumor cells has not been possible. There seems no doubt that the tumor cells produce a peptide hormone. Secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide and combinations of hormones are discussed. The results are contradictory. Theories concerning the formal and causal pathogenesis are only incomplete and unproved up to now.", "contents": "[The Verner-Morrison syndrome. The clinical picture and pathologic anatomy]. The Verner-Morrison Syndrome is a clinically defined entity caused by an islet cell tumor of the pancreas. More than 60 cases have been described so long. The syndrome is characterized by diarrhea, hypokalemia and hypochlorhydria. In addition to a diabetic disposition, raised calcium levels and skin alterations may be present. The diagnosis is a clinical one. A pancreatic tumor should be searched for and removed. Morphologically a benign and a maligne islet cell tumor or a diffuse hyperplasia of the islets of Langerhans can be found. Until now identification of the tumor cells has not been possible. There seems no doubt that the tumor cells produce a peptide hormone. Secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide and combinations of hormones are discussed. The results are contradictory. Theories concerning the formal and causal pathogenesis are only incomplete and unproved up to now."} {"id": "PMID:175212", "title": "An ultrastructural study of nuclear and centriolar configurations in multinucleated giant cells.", "content": "Multinucleated giant cells were examined with electron microscopy from (1) four peripheral giant cell granulomas of the jaws, (2) a central giant cell tumor of the maxilla, (3) five giant cell tumors of tendon sheath, (4) experimentally induced foreign body granulomas in rats, (5) a virus-induced sarcoma, and (6) osteoclasts from the mandibles of rats and (7) the femurs of hamsters. The purpose of the study was (1) to examine the location and arrangement of the nuclei and the centrioles of the multinuclueated cells and compare them with the osteoclast which has previously been thought to have a unique arrangement and (2) to observe whether the physical location of the centrioles and the nuclei were such that the nuclei could undergo mitosis within the cytoplasm. All of the multinucleated cells were found to have a similar arragnement of nuclear concentration areas and nucleus-free areas. A giant centrosphere containing multiple pairs of centrioles was found in the nucleus-free areas, unassociated with any particular nucleus. In the case of the foreign body giant cell and the osteoclast, this giant centrosphere was located very close to the foreign material or bone. When occasional single pairs of centrioles were found, they were located in the area of nuclear concentration, closely associated with a particular nucleus at the periphery. These findings have shown that a common centrosphere containing multiple centrioles is not an exclusive feature of the osteoclast as was previously thought. The findings suggest that a mononuclear cell containing a centriole pair fuses to the larger cell and maintains its centriole pair in close proximity to its nucleus for a short period of time, during which it may undergo mitotic activity. Eventually, the centrioles proceed to a common centrosphere whereas the nuclei aggregate in another area making further mitotic activity an unlikely possibility.", "contents": "An ultrastructural study of nuclear and centriolar configurations in multinucleated giant cells. Multinucleated giant cells were examined with electron microscopy from (1) four peripheral giant cell granulomas of the jaws, (2) a central giant cell tumor of the maxilla, (3) five giant cell tumors of tendon sheath, (4) experimentally induced foreign body granulomas in rats, (5) a virus-induced sarcoma, and (6) osteoclasts from the mandibles of rats and (7) the femurs of hamsters. The purpose of the study was (1) to examine the location and arrangement of the nuclei and the centrioles of the multinuclueated cells and compare them with the osteoclast which has previously been thought to have a unique arrangement and (2) to observe whether the physical location of the centrioles and the nuclei were such that the nuclei could undergo mitosis within the cytoplasm. All of the multinucleated cells were found to have a similar arragnement of nuclear concentration areas and nucleus-free areas. A giant centrosphere containing multiple pairs of centrioles was found in the nucleus-free areas, unassociated with any particular nucleus. In the case of the foreign body giant cell and the osteoclast, this giant centrosphere was located very close to the foreign material or bone. When occasional single pairs of centrioles were found, they were located in the area of nuclear concentration, closely associated with a particular nucleus at the periphery. These findings have shown that a common centrosphere containing multiple centrioles is not an exclusive feature of the osteoclast as was previously thought. The findings suggest that a mononuclear cell containing a centriole pair fuses to the larger cell and maintains its centriole pair in close proximity to its nucleus for a short period of time, during which it may undergo mitotic activity. Eventually, the centrioles proceed to a common centrosphere whereas the nuclei aggregate in another area making further mitotic activity an unlikely possibility."} {"id": "PMID:175213", "title": "Zonal changes in renal structure and phospholipid metabolism in potassium-deficient rats.", "content": "Morphologic alterations and membrane metabolism were studied in the kidneys of rats fed a low potassium diet. Transmission and scanning electron microscopy following perfusion-fixation of kidneys revealed that the earliest morphologic change occurs in cells of the papillary tip in which multivesicular bodies, a specific type to lysosome, appear after 1 day. Increased depletion leads to extension of the lesion to all cells of the papilla. After 1 week, a narrow band of hyperplasia in the inner red medulla appears; this band is characterized by adenomatous proliferation of intercalated and light cells and partial obstruction of collecting tubules. These alterations and cortical growth in the normal pattern result in increased renal weight. New membrane formation for lysosomes and growing cells was studied by measuring the rate of [14C]choline incorporation into phospholipid in slices from five zones of the kidney. In the papilla the rate increased 39 per cent after 18 hours, the earliest change detected. After 36 hours the rate increased in inner red medulla by 28 per cent, inner cortex by 25 per cent and outer cortex by 40 per cent. [14C]choline was a specific precursor of the three renal phospholipids, phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The relative distribution of the label did not change with growth induced by potassium depletion. The results indicate that potassium depletion induces early increases in the formation of cell membrane phospholipid which correlate with specific morphologic changes in different zones within the kidney.", "contents": "Zonal changes in renal structure and phospholipid metabolism in potassium-deficient rats. Morphologic alterations and membrane metabolism were studied in the kidneys of rats fed a low potassium diet. Transmission and scanning electron microscopy following perfusion-fixation of kidneys revealed that the earliest morphologic change occurs in cells of the papillary tip in which multivesicular bodies, a specific type to lysosome, appear after 1 day. Increased depletion leads to extension of the lesion to all cells of the papilla. After 1 week, a narrow band of hyperplasia in the inner red medulla appears; this band is characterized by adenomatous proliferation of intercalated and light cells and partial obstruction of collecting tubules. These alterations and cortical growth in the normal pattern result in increased renal weight. New membrane formation for lysosomes and growing cells was studied by measuring the rate of [14C]choline incorporation into phospholipid in slices from five zones of the kidney. In the papilla the rate increased 39 per cent after 18 hours, the earliest change detected. After 36 hours the rate increased in inner red medulla by 28 per cent, inner cortex by 25 per cent and outer cortex by 40 per cent. [14C]choline was a specific precursor of the three renal phospholipids, phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The relative distribution of the label did not change with growth induced by potassium depletion. The results indicate that potassium depletion induces early increases in the formation of cell membrane phospholipid which correlate with specific morphologic changes in different zones within the kidney."} {"id": "PMID:175214", "title": "Proliferation of endothelial cells in estrogen-stimulated rat liver. A light and electron microscopic cytochemical study.", "content": "The mononuclear phagocytes (Kupffer cells) in the normal rat liver can be distinguished from the endothelial cells on the basis of their endogenous peroxidase activity in the endoplasmic reticulum and their exclusive ability to phagocytose large (0.81 mum.) latex particles. Using these cellular markers we have investigated the effects of an estrogen upon the mitotic activity and the ultrastructure of individual types of littoral cells in the rat liver. Adult female rats received a single 10-mg. injection of diethylstilbestrol, and at daily intervals up to 6 days their livers were fixed by perfusion and processed for localization of peroxidase. Mitotic figures were rare in untreated control animals, but dividing littoral cells with both positive and negative peroxidase reaction could be identified. The exclusive localization of injected latex particles in dividing peroxidase-positive cells indicated that peroxidase reaction identified the Kupffer cells not only in the interphase but also during the mitotic division. In estrogen-treated animals there was a sharp rise in the mitotic activity of littoral cells; the activity reached its peak on the 3rd day and returned to normal levels on the 6th day after the initial injection. A breakdown of the dividing cells on the basis of their peroxidase reactivity revealed that nearly the entire population of dividing cells consisted of peroxidase-negative endothelial cells. In addition, numerous hyperactive Kupffer cells containing large phagolysosomes with phagocytosed peripheral blood cells and latex particles were seen. Intermediate cell-types with cytochemical features between Kupffer cells and endothelial cells or between monocytes and Kupffer cells were not encountered. Because of the limited phagocytic capacity of hepatic endothelial cells, our observations would provide morphologic evidence in support of previous physiologic studies, indicating that estrogen treatment has little or no effect upon the particle clearing function of the reticuloendothelial system in rats. The rare but clear demonstration of dividing Kupffer cells in liver sinusoids would indicate that these cells are capable of self-replication in situ. Finally, our observations suggest that estrogens may play an important role in the pathophysiology of endothelial cells.", "contents": "Proliferation of endothelial cells in estrogen-stimulated rat liver. A light and electron microscopic cytochemical study. The mononuclear phagocytes (Kupffer cells) in the normal rat liver can be distinguished from the endothelial cells on the basis of their endogenous peroxidase activity in the endoplasmic reticulum and their exclusive ability to phagocytose large (0.81 mum.) latex particles. Using these cellular markers we have investigated the effects of an estrogen upon the mitotic activity and the ultrastructure of individual types of littoral cells in the rat liver. Adult female rats received a single 10-mg. injection of diethylstilbestrol, and at daily intervals up to 6 days their livers were fixed by perfusion and processed for localization of peroxidase. Mitotic figures were rare in untreated control animals, but dividing littoral cells with both positive and negative peroxidase reaction could be identified. The exclusive localization of injected latex particles in dividing peroxidase-positive cells indicated that peroxidase reaction identified the Kupffer cells not only in the interphase but also during the mitotic division. In estrogen-treated animals there was a sharp rise in the mitotic activity of littoral cells; the activity reached its peak on the 3rd day and returned to normal levels on the 6th day after the initial injection. A breakdown of the dividing cells on the basis of their peroxidase reactivity revealed that nearly the entire population of dividing cells consisted of peroxidase-negative endothelial cells. In addition, numerous hyperactive Kupffer cells containing large phagolysosomes with phagocytosed peripheral blood cells and latex particles were seen. Intermediate cell-types with cytochemical features between Kupffer cells and endothelial cells or between monocytes and Kupffer cells were not encountered. Because of the limited phagocytic capacity of hepatic endothelial cells, our observations would provide morphologic evidence in support of previous physiologic studies, indicating that estrogen treatment has little or no effect upon the particle clearing function of the reticuloendothelial system in rats. The rare but clear demonstration of dividing Kupffer cells in liver sinusoids would indicate that these cells are capable of self-replication in situ. Finally, our observations suggest that estrogens may play an important role in the pathophysiology of endothelial cells."} {"id": "PMID:175215", "title": "Abnormally large lamellar bodies in type II pneumocytes in Chediak-Higashi syndrome in beige mice.", "content": "Lamellar bodies in type II pneumocytes are markedly enlarged in beige mice. The irregular shapes of some of these enlarged specialized lysosomes suggest fusion of smaller ellipsoidal bodies to form the giant organelles, consistent with the proposal of others for the mechanism of formation of abnormal lysosomes in Chediak-Higashi syndrome. Examination of the structure of lamellar bodies by the freeze-fracture technique reveals highly ordered stacking or concentric wrapping of the constituent lamellae. The corrugated patterns evident on the surfaces of normal lamellae are also present in Chediak-Higashi syndrome lamellae. Both normal and Chediak-Higashi syndrome lamellae appear free of typical intramembranous particles. The corrugations seen in the lamellae closely resemble those seen on freeze-fracture of dispersions of lecithin in water.", "contents": "Abnormally large lamellar bodies in type II pneumocytes in Chediak-Higashi syndrome in beige mice. Lamellar bodies in type II pneumocytes are markedly enlarged in beige mice. The irregular shapes of some of these enlarged specialized lysosomes suggest fusion of smaller ellipsoidal bodies to form the giant organelles, consistent with the proposal of others for the mechanism of formation of abnormal lysosomes in Chediak-Higashi syndrome. Examination of the structure of lamellar bodies by the freeze-fracture technique reveals highly ordered stacking or concentric wrapping of the constituent lamellae. The corrugated patterns evident on the surfaces of normal lamellae are also present in Chediak-Higashi syndrome lamellae. Both normal and Chediak-Higashi syndrome lamellae appear free of typical intramembranous particles. The corrugations seen in the lamellae closely resemble those seen on freeze-fracture of dispersions of lecithin in water."} {"id": "PMID:175211", "title": "[Pathophysiology of prolonged hypokinesia].", "content": "Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.", "contents": "[Pathophysiology of prolonged hypokinesia]. Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work."} {"id": "PMID:175216", "title": "Human cord blood lymphocytes. Ultrastructural and immunologic surface marker characteristics; a comparison with B- and T-cell lymphomas.", "content": "The ultrastructural and surface marker characteristics of human cord blood lymphocytes were studied. These properties were compared with those in cells of patients in the leukemic phase of both malignant lymphoma, poorly differentiated lymphocytic type, and mycosis fungoides. Nuclear folding in cord blood lymphocytes was similar to that seen in lymphocytes of patients with malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides. Surface marker characteristics of cord blood lymphocytes included increased percentages of surface IgD on cells bearing surface immunoglobulins and decreased percentages of E-rosette-forming cells. The hypothesis that both malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides represent an arrest in the normal lymphocyte maturation sequence is discussed.", "contents": "Human cord blood lymphocytes. Ultrastructural and immunologic surface marker characteristics; a comparison with B- and T-cell lymphomas. The ultrastructural and surface marker characteristics of human cord blood lymphocytes were studied. These properties were compared with those in cells of patients in the leukemic phase of both malignant lymphoma, poorly differentiated lymphocytic type, and mycosis fungoides. Nuclear folding in cord blood lymphocytes was similar to that seen in lymphocytes of patients with malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides. Surface marker characteristics of cord blood lymphocytes included increased percentages of surface IgD on cells bearing surface immunoglobulins and decreased percentages of E-rosette-forming cells. The hypothesis that both malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides represent an arrest in the normal lymphocyte maturation sequence is discussed."} {"id": "PMID:175217", "title": "The effects of long chain free fatty acids on human neutrophil function and structure.", "content": "Neutrophils from healthy volunteers were isolated and incubated with varying concentrations of albumin-bound long chain free fatty acids. Standard in vitro function tests including phagocytosis, bactericidal activity, and chemotaxis were performed after the incubation. It was found that unsaturated fatty acid (oleic acid) caused no changes in bactericidal activity and only moderate decreases in phagocytosis and chemotaxis at very high concentrations. Saturated fatty acid (palmitic acid) produced, at high concentrations, virtually complete inhibition of chemotaxis and moderate depression of phagocytosis and bactericidal ability. Most significantly, lower concentrations of saturated free fatty acids, within the range reported clinically in various diseases, caused a marked inhibition of chemotaxis. These functional disturbances were associated with ultrastructural alterations. Neutrophils treated with oleic acid contained numerous cytoplasmic neutral lipid droplets. Neutrophils incubated with palmitic acid showed elongated cleftlike dilations of the endoplasmic reticulum and degenerative degranulated cytoplasmic areas. It is postulated that these represent crystallization of excess saturated free fatty acids or triglyceride which interfere with chemotaxis, either mechanically or by causing cell injury.", "contents": "The effects of long chain free fatty acids on human neutrophil function and structure. Neutrophils from healthy volunteers were isolated and incubated with varying concentrations of albumin-bound long chain free fatty acids. Standard in vitro function tests including phagocytosis, bactericidal activity, and chemotaxis were performed after the incubation. It was found that unsaturated fatty acid (oleic acid) caused no changes in bactericidal activity and only moderate decreases in phagocytosis and chemotaxis at very high concentrations. Saturated fatty acid (palmitic acid) produced, at high concentrations, virtually complete inhibition of chemotaxis and moderate depression of phagocytosis and bactericidal ability. Most significantly, lower concentrations of saturated free fatty acids, within the range reported clinically in various diseases, caused a marked inhibition of chemotaxis. These functional disturbances were associated with ultrastructural alterations. Neutrophils treated with oleic acid contained numerous cytoplasmic neutral lipid droplets. Neutrophils incubated with palmitic acid showed elongated cleftlike dilations of the endoplasmic reticulum and degenerative degranulated cytoplasmic areas. It is postulated that these represent crystallization of excess saturated free fatty acids or triglyceride which interfere with chemotaxis, either mechanically or by causing cell injury."} {"id": "PMID:175220", "title": "Desmoid tumor associated with cystosarcoma phyllodes of the breast.", "content": "A case of desmoid tumor of 17 years' duration associated with cystosarcoma phyllodes of 17 months' duration is presented. Good initial response to radiation therapy of the desmoid tumor was shown. Poor response of cytosarcoma phyllodes to radiation therapy was noted. A comparison between the similarities and differences of the two tumors is presented.", "contents": "Desmoid tumor associated with cystosarcoma phyllodes of the breast. A case of desmoid tumor of 17 years' duration associated with cystosarcoma phyllodes of 17 months' duration is presented. Good initial response to radiation therapy of the desmoid tumor was shown. Poor response of cytosarcoma phyllodes to radiation therapy was noted. A comparison between the similarities and differences of the two tumors is presented."} {"id": "PMID:175223", "title": "[Ultrastructural and cytological study of atypical fibroxanthoma].", "content": "A case of atypical fibroxanthoma of the skin is related. Ulstrastructural findings include: fibroblast-like cells, histiocytic-like cells, xanthomatous cells, and multinucleated cells. Strikingly similar findings were found by Fu and cols. (1975) in four cases of malignant fibrous histiocytoma. The authors postulated that both tumours could represent different aspects of a single proliferating process.", "contents": "[Ultrastructural and cytological study of atypical fibroxanthoma]. A case of atypical fibroxanthoma of the skin is related. Ulstrastructural findings include: fibroblast-like cells, histiocytic-like cells, xanthomatous cells, and multinucleated cells. Strikingly similar findings were found by Fu and cols. (1975) in four cases of malignant fibrous histiocytoma. The authors postulated that both tumours could represent different aspects of a single proliferating process."} {"id": "PMID:175224", "title": "[Histiocytofibroma. Spontaneous regression, leaving skin atrophy].", "content": "Three cases of histiocytoma with atypical course are described by the authors. Two of them dissappeared completely or almost completely leaving a scar where some remnants of the original tumor were present. In the third patient the tumor grew deeply in the dermis leaving the same atrophic scaring on the surface. By palpation the original tumor was also detectable.", "contents": "[Histiocytofibroma. Spontaneous regression, leaving skin atrophy]. Three cases of histiocytoma with atypical course are described by the authors. Two of them dissappeared completely or almost completely leaving a scar where some remnants of the original tumor were present. In the third patient the tumor grew deeply in the dermis leaving the same atrophic scaring on the surface. By palpation the original tumor was also detectable."} {"id": "PMID:175222", "title": "Diagnostic importance of lipoprotein-X (LP-X) in the diagnosis of cholestasis.", "content": "In 317 patients with diseases of the liver and bile tract the authors determined LP-X in the serum and the obtained results were compared with the morphological findings in liver tissue or intraoperative examination of the extrahepatic bile ducts. Int he same patients serum bilirubin, total cholesterol, alkaline phosphatase activity, gamma-glutamyltranspeptidase and leucylaminopeptidase activity were determined. In the light of these results the authors believe that detection of LP-X in the serum is a sensitive and specific method in the diagnosis of cholestasis and that it is of greater usefulness than determination of alkaline phosphatase activity. Determinations of other biochemical parameters is of small diagnostic importance in these cases.", "contents": "Diagnostic importance of lipoprotein-X (LP-X) in the diagnosis of cholestasis. In 317 patients with diseases of the liver and bile tract the authors determined LP-X in the serum and the obtained results were compared with the morphological findings in liver tissue or intraoperative examination of the extrahepatic bile ducts. Int he same patients serum bilirubin, total cholesterol, alkaline phosphatase activity, gamma-glutamyltranspeptidase and leucylaminopeptidase activity were determined. In the light of these results the authors believe that detection of LP-X in the serum is a sensitive and specific method in the diagnosis of cholestasis and that it is of greater usefulness than determination of alkaline phosphatase activity. Determinations of other biochemical parameters is of small diagnostic importance in these cases."} {"id": "PMID:175228", "title": "[Xeroradiography of the neck and of the salivary glands (author's transl)].", "content": "This paper describes the possibilities of xeroradiography in the neck area. 6 clinical samples demonstrate the usefulness of this method in the diagnosis of different disorders of the neck organs. The advantage of xeroradiography is that in contrast to conventional x-ray technique all tissue densities are represented in a single image. The problems of the different radiation exposure are discussed.", "contents": "[Xeroradiography of the neck and of the salivary glands (author's transl)]. This paper describes the possibilities of xeroradiography in the neck area. 6 clinical samples demonstrate the usefulness of this method in the diagnosis of different disorders of the neck organs. The advantage of xeroradiography is that in contrast to conventional x-ray technique all tissue densities are represented in a single image. The problems of the different radiation exposure are discussed."} {"id": "PMID:175229", "title": "[Clinical diagnosis of the auditory pathway using different acoustical evoked responses (author's transl)].", "content": "Evoked responses originating from cochlea, brain stem, and cortex are clinically used for differential diagnosis of hearing losses. The diagnostic range and the reliability of the different ERA methods are discussed. In our clinic brain stem potentials recorded by a nonsurgical method have been used as a routine audiometric test in more than 900 cases. The procedure has proved to be easier than electrocochleography and gives nearly the same information about cochlear and middle ear function if there is no VIIIth nerve or lower brain stem damage. For topical diagnosis of the lower auditory pathway additional recording of ECoG is necessary. In the examination of a cortical deafness the recording of brain stem potentials yields the same result as the electrocochleography according to Aran (Fig. 2). In a case of an Apallic syndrome (Fig. 3) brain stem potentials are found only for high intensity clicks, and latencies are abnormally increased. The cochlear potentials simultaneously recorded from the promontory are quite normal. So damage of the brain stem is confirmed.", "contents": "[Clinical diagnosis of the auditory pathway using different acoustical evoked responses (author's transl)]. Evoked responses originating from cochlea, brain stem, and cortex are clinically used for differential diagnosis of hearing losses. The diagnostic range and the reliability of the different ERA methods are discussed. In our clinic brain stem potentials recorded by a nonsurgical method have been used as a routine audiometric test in more than 900 cases. The procedure has proved to be easier than electrocochleography and gives nearly the same information about cochlear and middle ear function if there is no VIIIth nerve or lower brain stem damage. For topical diagnosis of the lower auditory pathway additional recording of ECoG is necessary. In the examination of a cortical deafness the recording of brain stem potentials yields the same result as the electrocochleography according to Aran (Fig. 2). In a case of an Apallic syndrome (Fig. 3) brain stem potentials are found only for high intensity clicks, and latencies are abnormally increased. The cochlear potentials simultaneously recorded from the promontory are quite normal. So damage of the brain stem is confirmed."} {"id": "PMID:175231", "title": "Specific formation of arachidonoyl phosphatidylinositol from 1-acyl-sn-glycero-3-phosphorylinositol in rat liver.", "content": "The conversion of 1-acyl-sn-glycero-3-phosphorylinositol-3H into phosphatidylinositol-3H was studied using rat liver microsomal and homogenate preparations. The nature of the molecular species of phosphatidyl inositol so formed in the absence of added acyl moieties was determined after fractionating the radioactive product by means of argentation thin layer chromatography. In other experiments, the possible specificity of the microsomal acyl-CoA:1-acyl-sn-glycero-3-phosphorylinositol acyltransferase towards different acyl-CoA derivatives was investigated. Maximum conversion of 1-acyl GPI to the diacyl analogue was dependent on the addition of adenosine triphosphate and CoA when exogensou acyl groups were omitted from the incubation medium. Under these latter conditions, the tetraenoic species comprised 56-74% of the total molecular species of newly-formed phosphatidylinositol. The microsomal acyl-CoA:1-acyl-sn-glycero-3-phosphorylinositol acyltransferase showed a marked preference for arachidonoyl-CoA. The present results suggest that the enrichment of rat liver phosphatidyl inositol in arachidonic acid may arise when 1-acyl-sn-glycero-3-phosphorylinositol is acylated to form phosphatidylinositol.", "contents": "Specific formation of arachidonoyl phosphatidylinositol from 1-acyl-sn-glycero-3-phosphorylinositol in rat liver. The conversion of 1-acyl-sn-glycero-3-phosphorylinositol-3H into phosphatidylinositol-3H was studied using rat liver microsomal and homogenate preparations. The nature of the molecular species of phosphatidyl inositol so formed in the absence of added acyl moieties was determined after fractionating the radioactive product by means of argentation thin layer chromatography. In other experiments, the possible specificity of the microsomal acyl-CoA:1-acyl-sn-glycero-3-phosphorylinositol acyltransferase towards different acyl-CoA derivatives was investigated. Maximum conversion of 1-acyl GPI to the diacyl analogue was dependent on the addition of adenosine triphosphate and CoA when exogensou acyl groups were omitted from the incubation medium. Under these latter conditions, the tetraenoic species comprised 56-74% of the total molecular species of newly-formed phosphatidylinositol. The microsomal acyl-CoA:1-acyl-sn-glycero-3-phosphorylinositol acyltransferase showed a marked preference for arachidonoyl-CoA. The present results suggest that the enrichment of rat liver phosphatidyl inositol in arachidonic acid may arise when 1-acyl-sn-glycero-3-phosphorylinositol is acylated to form phosphatidylinositol."} {"id": "PMID:175232", "title": "Effect of dietary polyunsaturated pork on plasma lipids and sterol excretion in man.", "content": "Pork, enriched in linoleic acid content, was compared iwth conventional pork in the diet of three human subjects with respect to the plasma cholesterol concentration and the excretion in feces of neutral sterols and bile acids. Since the fatty acids in pork glyceride have an unusual positional distribution, the redistribution that might occur during the absorption and disposition of a fat meal was also studied. The plasma cholesterol was lower with polyunsaturated pork, the difference, 14 mg/100 ml plasma, being of the order expected from the change in polyunsaturated to saturated fatty acid ratio. On average, the excretion of neutral sterols was 57% greater with polyunsaturated than with conventional pork in all three subjects, and in this respect the results resembled the findings with polyunsaturated ruminant fats. During the absorption of pork fat, the high proportion of palmitate in the 2 position of lard triglyceride served as a useful marker, since human triglyceride carries mainly unsaturated fatty acids in that position. There were stepwise changes in the fatty acid composition at the 2 position of triglyceride as the fat was absorbed, transported through, and cleared from plasma, the palmitate being gradually replaced by oleate and linoleate. By contrast, the total fatty acid profile in the triglyceride changed relatively little, implying selective reacylation with palmitate at the 1 and/or 3 position. During the clearing of dietary triglyceride, the porcine triglyceride was thus converted to the form occuring in humans.", "contents": "Effect of dietary polyunsaturated pork on plasma lipids and sterol excretion in man. Pork, enriched in linoleic acid content, was compared iwth conventional pork in the diet of three human subjects with respect to the plasma cholesterol concentration and the excretion in feces of neutral sterols and bile acids. Since the fatty acids in pork glyceride have an unusual positional distribution, the redistribution that might occur during the absorption and disposition of a fat meal was also studied. The plasma cholesterol was lower with polyunsaturated pork, the difference, 14 mg/100 ml plasma, being of the order expected from the change in polyunsaturated to saturated fatty acid ratio. On average, the excretion of neutral sterols was 57% greater with polyunsaturated than with conventional pork in all three subjects, and in this respect the results resembled the findings with polyunsaturated ruminant fats. During the absorption of pork fat, the high proportion of palmitate in the 2 position of lard triglyceride served as a useful marker, since human triglyceride carries mainly unsaturated fatty acids in that position. There were stepwise changes in the fatty acid composition at the 2 position of triglyceride as the fat was absorbed, transported through, and cleared from plasma, the palmitate being gradually replaced by oleate and linoleate. By contrast, the total fatty acid profile in the triglyceride changed relatively little, implying selective reacylation with palmitate at the 1 and/or 3 position. During the clearing of dietary triglyceride, the porcine triglyceride was thus converted to the form occuring in humans."} {"id": "PMID:175233", "title": "Lung lamellar bodies lack certain key enzymes of phospholipid metabolism.", "content": "Palmitoyl CoA-glycerol-3-phosphate acyltransferase, phosphatidate phosphohydrolase, and phospholipase A were assayed in subcellular fractions of rat lung, including lamellar bodies, the putative site of storage and secretion of lung surfactant. The specific activity of each of these enzymes in lamellar bodies was relatively low and could be entirely accounted for by a small contamination of the lamellar bodies fraction by microsomes, as quantitated by the presence of the microsomal marker reduced triphosphopyridine nucleotide cytochrome c reductase. These data indicate that lamellar bodies are not the site of synthesis of the lipid component of pulmonary surfactant by pathways involving these enzymes.", "contents": "Lung lamellar bodies lack certain key enzymes of phospholipid metabolism. Palmitoyl CoA-glycerol-3-phosphate acyltransferase, phosphatidate phosphohydrolase, and phospholipase A were assayed in subcellular fractions of rat lung, including lamellar bodies, the putative site of storage and secretion of lung surfactant. The specific activity of each of these enzymes in lamellar bodies was relatively low and could be entirely accounted for by a small contamination of the lamellar bodies fraction by microsomes, as quantitated by the presence of the microsomal marker reduced triphosphopyridine nucleotide cytochrome c reductase. These data indicate that lamellar bodies are not the site of synthesis of the lipid component of pulmonary surfactant by pathways involving these enzymes."} {"id": "PMID:175234", "title": "Cholesteryl ester metabolism in tissue culture cells: II. Source of accumulated esterified cholesterol in Fu5AH rat hepatoma cells.", "content": "Previous investigations had demonstrated that Fu5AH rat hepatoma cells accumulated large quantities of esterified cholesterol when grown in hyperlipemic rabbit serum. The present investigation has determined the sources of the cellular esterified cholesterol when the cells were grown in hyperlipemic serum. Cellular esterification of endogenous and exogenous free cholesterol contributed 10% and 30%, respectively. The remaining 60% of the accumulated cellular esterfied cholesterol was derived from exogenous (serum) cholesteryl esters. Evidence for the hydrolysis of a portion of the incorporated esterified cholesterol is presented. A stimulation of free cholesterol incorporation and cellular esterification is elicited by hyperlipemic serum and serum lipoproteins when compared to normolipemic serum present at equivalent exogenous cholesterol concentrations. The effect of hyperlipemic serum is reduced by Tween-80 and Triton WR-1339. Comparative data on esterified cholesterol accumulation, free cholesterol incorporation, and cellular cholesterol esterification in Fu5-5 rat hepatoma cells, L-cells, and rabbit aortic medial cells are presented.", "contents": "Cholesteryl ester metabolism in tissue culture cells: II. Source of accumulated esterified cholesterol in Fu5AH rat hepatoma cells. Previous investigations had demonstrated that Fu5AH rat hepatoma cells accumulated large quantities of esterified cholesterol when grown in hyperlipemic rabbit serum. The present investigation has determined the sources of the cellular esterified cholesterol when the cells were grown in hyperlipemic serum. Cellular esterification of endogenous and exogenous free cholesterol contributed 10% and 30%, respectively. The remaining 60% of the accumulated cellular esterfied cholesterol was derived from exogenous (serum) cholesteryl esters. Evidence for the hydrolysis of a portion of the incorporated esterified cholesterol is presented. A stimulation of free cholesterol incorporation and cellular esterification is elicited by hyperlipemic serum and serum lipoproteins when compared to normolipemic serum present at equivalent exogenous cholesterol concentrations. The effect of hyperlipemic serum is reduced by Tween-80 and Triton WR-1339. Comparative data on esterified cholesterol accumulation, free cholesterol incorporation, and cellular cholesterol esterification in Fu5-5 rat hepatoma cells, L-cells, and rabbit aortic medial cells are presented."} {"id": "PMID:175237", "title": "Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding.", "content": "The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle. The hormone had, however, no effect on the activity of various enzymes involved in amino acid catabolism in muscle. In nephrosis, another condition of muscle wasting, the level of several muscle amino acids were also reduced to a lesser extent. Cortisol and triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic proteins in muscle. Binding of the labeled hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for glucocorticoids, and that muscle responsiveness involves binding of the active hormones to cytoplasmic receptor sites.", "contents": "Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding. The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle. The hormone had, however, no effect on the activity of various enzymes involved in amino acid catabolism in muscle. In nephrosis, another condition of muscle wasting, the level of several muscle amino acids were also reduced to a lesser extent. Cortisol and triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic proteins in muscle. Binding of the labeled hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for glucocorticoids, and that muscle responsiveness involves binding of the active hormones to cytoplasmic receptor sites."} {"id": "PMID:175238", "title": "Steroidogenic responses to varying parenteral routes of administered (alpha 1-18) ACTH.", "content": "In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation.", "contents": "Steroidogenic responses to varying parenteral routes of administered (alpha 1-18) ACTH. In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation."} {"id": "PMID:175239", "title": "On the lipolytic action of parathyroid hormone in man.", "content": "An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.", "contents": "On the lipolytic action of parathyroid hormone in man. An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism."} {"id": "PMID:175240", "title": "Alterations in levels and interrelations of plasma apolipoproteins induced by diet.", "content": "Diets high in carbohydrates increase the rates of hepatic secretion of VLDL in man. VLDL particles are secreted in greater numbers; they also tend to contain more triglycerides and to be larger in size. Comparable changes in intestinal secretion of chylomicrons and VLDL accompany fat absorption. We studied the metabolism of the ApoC apoproteins under these circumstances because in vitro studies suggest that these apoproteins may play important roles in the catabolism of VLDL. ApoA-I and ApoB were also examined because of their importance in HDL and VLDL structure, respectively. The fasting plasmas of 16 normolipemic young adults were examined before and after they had been fed high carbohydrate diets for 4-5 days. ApoA-I and ApoB were measured by radioimmunoassay. The relative proportions of ApoC-II and ApoC-III in VLDL were determined by disc gel electrophoresis. Lipids in plasma and in individual lipoproteins were determined chemically. Lipoproteins were isolated by ultracentrifugal and precipitation methods. VLDL-TG and VLDL-chol and VLDL-protein rose by factors of 2.4, 1.67, and 1.88, respectively. (Final value divided by initial value.) Since TG rose more than the others, VLDL became enriched by TG. LDL-chol fell by a factor of 0.78 while LDL-TG and LDL-ApoB remained constant, i.e., LDL became relatively enriched in TG and ApoB. HDL-TG rose by 1.42 and HDL-chol fell by 0.74, i.e., HDL too became TG enriched. Plasma Apo-A-I fell by 0.84. Thus, there were alterations in both the levels and compositions of all lipoproteins. The proportion of ApoC-II relative to ApoC-III in VLDL increased in each subject on the carbohydrate diet (mean rise was 1.55-fold). The increases in ApoC were detectable after as little as 48 hr of diet, and the same results were obtained in two people who were each tested twice on two separate occasions several months apart. Thus, the changes in ApoC were reproducible. Proportions of ApoC-II were greater in SF greater than 400 than in SF 20-400 subfractions of VLDL on ad lib diets. Proportions of ApoC-II rose in both density subfractions on carbohydrate diets. The changes in both subfractions suggest that rises of ApoC-II in total VLDL (SF greater than 20) fraction were not due solely to the accumulation of SF greater than 400 particles of unaltered ApoC composition in postdiet plasma. The changes following carbohydrate could have been due to secretion of altered lipoproteins or due to diet induced alterations in apoprotein catabolism. Three subjects were given 150 gm of corn oil to drink. Lipoproteins were analyzed, as above, at 0 and 3-12 hr after the drink. In spite of several-fold rises in the SF greater than 20 TG and proteins, the relative proportions of ApoC-II and ApoC-III remained constant. Thus, an acute dietary fat load and 2-4 days of carbohydrate diets provoked different responses. The fluctuations in the levels and relative proportions of ApoC support the notion that the ApoC group may have importance in vivo in the metabolism of VLDL.", "contents": "Alterations in levels and interrelations of plasma apolipoproteins induced by diet. Diets high in carbohydrates increase the rates of hepatic secretion of VLDL in man. VLDL particles are secreted in greater numbers; they also tend to contain more triglycerides and to be larger in size. Comparable changes in intestinal secretion of chylomicrons and VLDL accompany fat absorption. We studied the metabolism of the ApoC apoproteins under these circumstances because in vitro studies suggest that these apoproteins may play important roles in the catabolism of VLDL. ApoA-I and ApoB were also examined because of their importance in HDL and VLDL structure, respectively. The fasting plasmas of 16 normolipemic young adults were examined before and after they had been fed high carbohydrate diets for 4-5 days. ApoA-I and ApoB were measured by radioimmunoassay. The relative proportions of ApoC-II and ApoC-III in VLDL were determined by disc gel electrophoresis. Lipids in plasma and in individual lipoproteins were determined chemically. Lipoproteins were isolated by ultracentrifugal and precipitation methods. VLDL-TG and VLDL-chol and VLDL-protein rose by factors of 2.4, 1.67, and 1.88, respectively. (Final value divided by initial value.) Since TG rose more than the others, VLDL became enriched by TG. LDL-chol fell by a factor of 0.78 while LDL-TG and LDL-ApoB remained constant, i.e., LDL became relatively enriched in TG and ApoB. HDL-TG rose by 1.42 and HDL-chol fell by 0.74, i.e., HDL too became TG enriched. Plasma Apo-A-I fell by 0.84. Thus, there were alterations in both the levels and compositions of all lipoproteins. The proportion of ApoC-II relative to ApoC-III in VLDL increased in each subject on the carbohydrate diet (mean rise was 1.55-fold). The increases in ApoC were detectable after as little as 48 hr of diet, and the same results were obtained in two people who were each tested twice on two separate occasions several months apart. Thus, the changes in ApoC were reproducible. Proportions of ApoC-II were greater in SF greater than 400 than in SF 20-400 subfractions of VLDL on ad lib diets. Proportions of ApoC-II rose in both density subfractions on carbohydrate diets. The changes in both subfractions suggest that rises of ApoC-II in total VLDL (SF greater than 20) fraction were not due solely to the accumulation of SF greater than 400 particles of unaltered ApoC composition in postdiet plasma. The changes following carbohydrate could have been due to secretion of altered lipoproteins or due to diet induced alterations in apoprotein catabolism. Three subjects were given 150 gm of corn oil to drink. Lipoproteins were analyzed, as above, at 0 and 3-12 hr after the drink. In spite of several-fold rises in the SF greater than 20 TG and proteins, the relative proportions of ApoC-II and ApoC-III remained constant. Thus, an acute dietary fat load and 2-4 days of carbohydrate diets provoked different responses. The fluctuations in the levels and relative proportions of ApoC support the notion that the ApoC group may have importance in vivo in the metabolism of VLDL."} {"id": "PMID:175241", "title": "Inhibitory effect of somatostatin on dibutyryl cyclic AMP-induced insulin and growth hormone release in human subjects.", "content": "The effect of somatostatin on the responses of blood glucose, plasma immunoreactive insulin (IRI), growth hormone (GH), and free fatty acids (FFA) to the injection of dibutyryl cyclic AMP (DBC) was studied in six normal volunteers. DBC, when injected alone, induced a rapid increase in blood glucose and plasma IRI levels, while GH concentrations showed a less marked and more delayed increase and plasma FFA showed a clear downtrend. Somatostatin infusion suppressed the GH and IRI release induced by DBC, potentiated its hyperglycemic effect and changed the pattern of FFA. These results suggest that somatostatin inhibits hormone secretion distal to the generation of cyclic AMP.", "contents": "Inhibitory effect of somatostatin on dibutyryl cyclic AMP-induced insulin and growth hormone release in human subjects. The effect of somatostatin on the responses of blood glucose, plasma immunoreactive insulin (IRI), growth hormone (GH), and free fatty acids (FFA) to the injection of dibutyryl cyclic AMP (DBC) was studied in six normal volunteers. DBC, when injected alone, induced a rapid increase in blood glucose and plasma IRI levels, while GH concentrations showed a less marked and more delayed increase and plasma FFA showed a clear downtrend. Somatostatin infusion suppressed the GH and IRI release induced by DBC, potentiated its hyperglycemic effect and changed the pattern of FFA. These results suggest that somatostatin inhibits hormone secretion distal to the generation of cyclic AMP."} {"id": "PMID:175242", "title": "Pituitary regulation of human growth hormone binding sites in rat liver membranes.", "content": "We have studied the binding of 125I-human growth hormone (hGH) to crude 100,000 X g membrane preparations from rat liver, and have studied factors which might regulate the capacity and affinity of hGH binding sites. Membrane preparations have livers of pregnant rats bound between 8% and 18% of the 125I-hGH initially added, and 70%-80% of that bound was displaced by 1 mug of unlabeled hGH. Humans prolactin (hPrl) displaced 125 I-hGH in a manner parallel to hGH itself but with about one-third the potency. Ovine, porcine, and rat Prl, and rat and bovine GH were much less effective. Scatchard analysis of specific hGH binding by a variety of different rat liver membrane preparations revealed a single order of binding site in each case with a binding affinity of 0.93-1.62 X 10(-9) M-1. Membranes from pregnant rats had twice the binding capacity of membranes from nonpregnant female rats, and about six times the capacity of sites present in preparations from normal adult male rats and hypophysectomized (Hx) male or female rats. Female or male rats with extremely high circulating GH an Prl levels, due to the presence of transplantable GH/Prl secreting pituitary tumors showed a significantly greater binding capacity than did the pregnant rats. Estradiol (E2) treatment (25 mug/day for 10-12 days) of normal male rats led to an increase in specific hGH binding. Treatment of hypophysectomized male rats with bovine GH (100 or 500 mug/day) +/- E2 (25 mug/day) for 5-10 days stimulated both body weight gain and the incorporation of sulfate by cartilage from the treated rats, but no significant increase was observed in the characteristics of 125I-hGH binding. These results indicate that high levels of E2, GH, and/or Prl play an important role in the regulation of hGH binding sites in rat liver membranes. The restoration of binding sites in liver from hypophysectomized rats, however, apparently requires additional factors which are as yet unidentified. The role of the hGH binding sites in the physiologic actions of GH also remains to be determined.", "contents": "Pituitary regulation of human growth hormone binding sites in rat liver membranes. We have studied the binding of 125I-human growth hormone (hGH) to crude 100,000 X g membrane preparations from rat liver, and have studied factors which might regulate the capacity and affinity of hGH binding sites. Membrane preparations have livers of pregnant rats bound between 8% and 18% of the 125I-hGH initially added, and 70%-80% of that bound was displaced by 1 mug of unlabeled hGH. Humans prolactin (hPrl) displaced 125 I-hGH in a manner parallel to hGH itself but with about one-third the potency. Ovine, porcine, and rat Prl, and rat and bovine GH were much less effective. Scatchard analysis of specific hGH binding by a variety of different rat liver membrane preparations revealed a single order of binding site in each case with a binding affinity of 0.93-1.62 X 10(-9) M-1. Membranes from pregnant rats had twice the binding capacity of membranes from nonpregnant female rats, and about six times the capacity of sites present in preparations from normal adult male rats and hypophysectomized (Hx) male or female rats. Female or male rats with extremely high circulating GH an Prl levels, due to the presence of transplantable GH/Prl secreting pituitary tumors showed a significantly greater binding capacity than did the pregnant rats. Estradiol (E2) treatment (25 mug/day for 10-12 days) of normal male rats led to an increase in specific hGH binding. Treatment of hypophysectomized male rats with bovine GH (100 or 500 mug/day) +/- E2 (25 mug/day) for 5-10 days stimulated both body weight gain and the incorporation of sulfate by cartilage from the treated rats, but no significant increase was observed in the characteristics of 125I-hGH binding. These results indicate that high levels of E2, GH, and/or Prl play an important role in the regulation of hGH binding sites in rat liver membranes. The restoration of binding sites in liver from hypophysectomized rats, however, apparently requires additional factors which are as yet unidentified. The role of the hGH binding sites in the physiologic actions of GH also remains to be determined."} {"id": "PMID:175244", "title": "[Effect of endogenous respiration of Candida mycoderma on the operation of the cytochrome system and the oxidation of glucose, ethanol and acids of the Krebs cycle].", "content": "The kinetics of oxidation of glucose, ethanol, and acids of the Krebs cycle was studied in resting cells of Candida mycoderma which differed by the level of endogenous respiration (ER). The cells with ER close to zero oxidized glucose and ethanol almost at once and at a high rate. During oxidation of succinic or other acids of the Krebs cycle, QO2 was maximal only after a long period of adaptation (tad); a latent period (tlat) was observed sometimes during which assimilation of oxygen was either insignificant or not detected at all. The values of tad and tlat were much lower in the cells with high ER or upon preliminary introduction of small amounts of easily oxidized substrates (e. g. glucose or ethanol). During oxidation of succinate (citrate, malate or alpha-ketoglutarate) by the cells with ER close to zero, reduction of cytochrome c takes place only some time after the beginning of oxygen uptake. Such a delay suggests that oxidation of aforementioned substrates is initiated by some other electron carriers rather than by the cytochrome system.", "contents": "[Effect of endogenous respiration of Candida mycoderma on the operation of the cytochrome system and the oxidation of glucose, ethanol and acids of the Krebs cycle]. The kinetics of oxidation of glucose, ethanol, and acids of the Krebs cycle was studied in resting cells of Candida mycoderma which differed by the level of endogenous respiration (ER). The cells with ER close to zero oxidized glucose and ethanol almost at once and at a high rate. During oxidation of succinic or other acids of the Krebs cycle, QO2 was maximal only after a long period of adaptation (tad); a latent period (tlat) was observed sometimes during which assimilation of oxygen was either insignificant or not detected at all. The values of tad and tlat were much lower in the cells with high ER or upon preliminary introduction of small amounts of easily oxidized substrates (e. g. glucose or ethanol). During oxidation of succinate (citrate, malate or alpha-ketoglutarate) by the cells with ER close to zero, reduction of cytochrome c takes place only some time after the beginning of oxygen uptake. Such a delay suggests that oxidation of aforementioned substrates is initiated by some other electron carriers rather than by the cytochrome system."} {"id": "PMID:175258", "title": "Specificity of the stimulation of in vitro ribonucleic acid synthesis by guanosine 5'-diphosphate 3'-diphosphate.", "content": "The in vitro synthesis of ribonucleic acid (RNA) by S-30 extracts of Escherichia coli K-12 is stimulated from two-to fourfold by 0.16 mM to 0.32 mM guanosine 5'-diphosphate 3'-diphosphate (ppGpp) when either gammacI857St68h80 deoxyribonucleic acid (gammah80 DNA), gammah80dilv DNA or gammah80dlac DNA are employed as templates. Hybridization analysis of the 3H-RNA product transcribed from gammah80dilv DNA in the presence of ppGpp indicates that both bacteriophage- and bacterial-specific transcription is stimulated to an equivalent degree. In the absence of cyclic 3'-5'-adenosine monophosphate (cyclic AMP), correct lac-specifci RNA synthesis from gammah80dlac DNA is not stimulated by 0.32 mM ppGpp although total RNA synthesis is increased nearly twofold. In the presence of 0.5 mM cyclic AMP, correct lacspecific RNA synthesis is stimulated preferentially by ppGpp. These data suggest that ppGpp is capable of stimulating in vitro transcription in both a general and selective manner.", "contents": "Specificity of the stimulation of in vitro ribonucleic acid synthesis by guanosine 5'-diphosphate 3'-diphosphate. The in vitro synthesis of ribonucleic acid (RNA) by S-30 extracts of Escherichia coli K-12 is stimulated from two-to fourfold by 0.16 mM to 0.32 mM guanosine 5'-diphosphate 3'-diphosphate (ppGpp) when either gammacI857St68h80 deoxyribonucleic acid (gammah80 DNA), gammah80dilv DNA or gammah80dlac DNA are employed as templates. Hybridization analysis of the 3H-RNA product transcribed from gammah80dilv DNA in the presence of ppGpp indicates that both bacteriophage- and bacterial-specific transcription is stimulated to an equivalent degree. In the absence of cyclic 3'-5'-adenosine monophosphate (cyclic AMP), correct lac-specifci RNA synthesis from gammah80dlac DNA is not stimulated by 0.32 mM ppGpp although total RNA synthesis is increased nearly twofold. In the presence of 0.5 mM cyclic AMP, correct lacspecific RNA synthesis is stimulated preferentially by ppGpp. These data suggest that ppGpp is capable of stimulating in vitro transcription in both a general and selective manner."} {"id": "PMID:175259", "title": "DNA-cellulose column chromatography of phosphorylated nucleolar nonhistone proteins.", "content": "A salt-extraction procedure was used to isolate a nucleolar nonhistone protein fraction, containing [32P]phosphoserine, from the nucleoli of Novikoff hepatoma ascites cells. These proteins are similar in amino-acid composition to whole nuclear (chromosomal) nonhistone proteins. DNA-cellulose column chromatography showed that this fraction contains DNA-binding phosphoproteins, some of which will bind only to homologous (Novikoff) nucleolar or nuclear DNA.", "contents": "DNA-cellulose column chromatography of phosphorylated nucleolar nonhistone proteins. A salt-extraction procedure was used to isolate a nucleolar nonhistone protein fraction, containing [32P]phosphoserine, from the nucleoli of Novikoff hepatoma ascites cells. These proteins are similar in amino-acid composition to whole nuclear (chromosomal) nonhistone proteins. DNA-cellulose column chromatography showed that this fraction contains DNA-binding phosphoproteins, some of which will bind only to homologous (Novikoff) nucleolar or nuclear DNA."} {"id": "PMID:175260", "title": "Cucumber mosaic virus RNA contains 7-methyl guanosine at the 5'-terminus of all four RNA species.", "content": "Purified cucumber mosaic virus (CMV) RNA was reacted with NaIO4 and then [3H]KBH4 to label ends containing exposed 2',3'-hydroxyls. The four major RNA species were then fractionated by polyacrylamide gel electrophoresis. Analysis of digests of these RNAs by ribonucleases T1 plus T2, alkaline phosphatease, snake venom diesterase and nucleotide pyrophosphatase by means of paper electrophoresis and ion-exchange chromatography indicated that the sequence m7G(5')ppp(5')N was present at the 5'-end of 75-92% of all RNA molecules. In addition, about 90% of the 3'-ends terminated in either adenosine or cytidine.", "contents": "Cucumber mosaic virus RNA contains 7-methyl guanosine at the 5'-terminus of all four RNA species. Purified cucumber mosaic virus (CMV) RNA was reacted with NaIO4 and then [3H]KBH4 to label ends containing exposed 2',3'-hydroxyls. The four major RNA species were then fractionated by polyacrylamide gel electrophoresis. Analysis of digests of these RNAs by ribonucleases T1 plus T2, alkaline phosphatease, snake venom diesterase and nucleotide pyrophosphatase by means of paper electrophoresis and ion-exchange chromatography indicated that the sequence m7G(5')ppp(5')N was present at the 5'-end of 75-92% of all RNA molecules. In addition, about 90% of the 3'-ends terminated in either adenosine or cytidine."} {"id": "PMID:175266", "title": "Paget's disease of the breast.", "content": "Criteria of the morphological diagnosis as well as the histogenesis of the lesions in Paget's disease are presented; the authors claim that the initial lesion occurs in the lactiferous ducts, the skin being secondarily involved. Likewise, the dyskeratotic lesions are considered as secondary to the neoplastic process, either by neoplastic induction or by mobilization and proliferation of cancerous cells from lactiferous ducts. The utility of biopsies in all cases of nipple eczema, and of the histologic investigation of the profound tissues is pointed out. In this way the canalicular starting point in the vicinity of the nipple can be noticed.", "contents": "Paget's disease of the breast. Criteria of the morphological diagnosis as well as the histogenesis of the lesions in Paget's disease are presented; the authors claim that the initial lesion occurs in the lactiferous ducts, the skin being secondarily involved. Likewise, the dyskeratotic lesions are considered as secondary to the neoplastic process, either by neoplastic induction or by mobilization and proliferation of cancerous cells from lactiferous ducts. The utility of biopsies in all cases of nipple eczema, and of the histologic investigation of the profound tissues is pointed out. In this way the canalicular starting point in the vicinity of the nipple can be noticed."} {"id": "PMID:175262", "title": "[Study of the conformational changes of serum albumin molecules within a pre-denaturation temperature range by a spin probe technique].", "content": "To study conformational changes of protein molecules in a pre-denaturation temperature range, nitroxyl radicals adsorbed by a protein are suggested to be used. A spin probe technique is specially developed to be implied for this aim by using a probe specifically bound to the bovine serum albumin molecule, it was possible to reveal a dependence of the rotation correlation time of the adsorbed radical and the environment polarity on the temperature. The data obtained testify in favour of a change occurring in the intramolecular structure of the protein under study due to a temperature change within the pre-denaturation temperature range.", "contents": "[Study of the conformational changes of serum albumin molecules within a pre-denaturation temperature range by a spin probe technique]. To study conformational changes of protein molecules in a pre-denaturation temperature range, nitroxyl radicals adsorbed by a protein are suggested to be used. A spin probe technique is specially developed to be implied for this aim by using a probe specifically bound to the bovine serum albumin molecule, it was possible to reveal a dependence of the rotation correlation time of the adsorbed radical and the environment polarity on the temperature. The data obtained testify in favour of a change occurring in the intramolecular structure of the protein under study due to a temperature change within the pre-denaturation temperature range."} {"id": "PMID:175263", "title": "[Selected carboxymethylation of ferri-hemoglobin from insect larvae Chironomus thummi thummi].", "content": "Specific modification of the monomeric fraction III of ferri-hemoglobin from insect larvae Chironomus thummi thummi (Hb CTT) was studied on histidyl residues His-G19 (pK 4,8), His-E5 (pK 7,3) and Met-H22 at different pH using iodacetamide and spin label 2,2,6,6-tetramethyl-4-bromacethyl-piperidin-1-oxyl, an analogue of bromacetate. The analysis of the products of carboxymethylation (CM) showed that at pH 5,0 two products of modification CM-(His-G19)-Hb CTT, and CM-(Met-H22)-Hb CTT were obtained. In the case of modification at pH 7,2 with a spin label dicarboxymethylatid product CM-(His-G19)-CM (His-E5)-Hb CTT is obtained. In all products the degree of modification was one spin label per mole protein. Based on the data on the primery and tertiary structures Hb CTT and the results of the investigation, different reactivity of His-G19 and His-E5, as well as the cause of the absence of the product of carboxymethylation on His-G2 have been discussed. By analizing the absorption spectra of carboxymethylated derivatives of hemoglobin in the ultraviolet and visible region, as well as from the pH dependence curves of the absorption at Soret band in the interval pH 5,5-11,5 it has been shown that carboxymethylation of His-G19 and His E5 is not accompanied by any substantial disturbance of the structures of aquous-complexes Hb CTT. Modification of Met-H22 leads to strong changes in the absorption spectrum and to the absence of pH dependence of the absorption at Soret band, which indicates a change in the aquous-complexes Hb CTT structure.", "contents": "[Selected carboxymethylation of ferri-hemoglobin from insect larvae Chironomus thummi thummi]. Specific modification of the monomeric fraction III of ferri-hemoglobin from insect larvae Chironomus thummi thummi (Hb CTT) was studied on histidyl residues His-G19 (pK 4,8), His-E5 (pK 7,3) and Met-H22 at different pH using iodacetamide and spin label 2,2,6,6-tetramethyl-4-bromacethyl-piperidin-1-oxyl, an analogue of bromacetate. The analysis of the products of carboxymethylation (CM) showed that at pH 5,0 two products of modification CM-(His-G19)-Hb CTT, and CM-(Met-H22)-Hb CTT were obtained. In the case of modification at pH 7,2 with a spin label dicarboxymethylatid product CM-(His-G19)-CM (His-E5)-Hb CTT is obtained. In all products the degree of modification was one spin label per mole protein. Based on the data on the primery and tertiary structures Hb CTT and the results of the investigation, different reactivity of His-G19 and His-E5, as well as the cause of the absence of the product of carboxymethylation on His-G2 have been discussed. By analizing the absorption spectra of carboxymethylated derivatives of hemoglobin in the ultraviolet and visible region, as well as from the pH dependence curves of the absorption at Soret band in the interval pH 5,5-11,5 it has been shown that carboxymethylation of His-G19 and His E5 is not accompanied by any substantial disturbance of the structures of aquous-complexes Hb CTT. Modification of Met-H22 leads to strong changes in the absorption spectrum and to the absence of pH dependence of the absorption at Soret band, which indicates a change in the aquous-complexes Hb CTT structure."} {"id": "PMID:175268", "title": "Comparative mutagenic effects of ethyl methane-sulfonate, n-methyl-n'-nitro-n-nitrosoguanidine, ultraviolet radiation and caffeine on Dictyostelium discoideum.", "content": "A high frequency of morphogenetic mutants of Dictyostelium discoideum can be induced by treatment with MNNG under conditions which result in relatively low cell killing. Six temperature-sensitive growth mutants induced by this treatment were isolated by replica plating. Among these, five showed spontaneous reversion rates of 10(-4) to 10(-5). The mutagenic activity of ems, measured for the induction of both morphogenetic and temperature-sensitive mutants, was weaker than that of MNNG and UV radiation. High frequencies of morphogenetic mutants were obtained only with doses of UV irradiation that resulted in high killing of cells or spores. Caffeine, at concentrations that slightly decreased the growth rate of amoebae in axenic medium, induced morphogenetic defects and also enhanced the mutagenic effect of UV irradiation. However, all the aggregateless clones derived from caffeine treatment that were studied reverted to the wild-type phenotype after a variable number of clonal re-isolations.", "contents": "Comparative mutagenic effects of ethyl methane-sulfonate, n-methyl-n'-nitro-n-nitrosoguanidine, ultraviolet radiation and caffeine on Dictyostelium discoideum. A high frequency of morphogenetic mutants of Dictyostelium discoideum can be induced by treatment with MNNG under conditions which result in relatively low cell killing. Six temperature-sensitive growth mutants induced by this treatment were isolated by replica plating. Among these, five showed spontaneous reversion rates of 10(-4) to 10(-5). The mutagenic activity of ems, measured for the induction of both morphogenetic and temperature-sensitive mutants, was weaker than that of MNNG and UV radiation. High frequencies of morphogenetic mutants were obtained only with doses of UV irradiation that resulted in high killing of cells or spores. Caffeine, at concentrations that slightly decreased the growth rate of amoebae in axenic medium, induced morphogenetic defects and also enhanced the mutagenic effect of UV irradiation. However, all the aggregateless clones derived from caffeine treatment that were studied reverted to the wild-type phenotype after a variable number of clonal re-isolations."} {"id": "PMID:175264", "title": "[Specific modification of phenylalanine:tRNA-ligases of E. coli MRE-600 with N-chlorambucilyl-14c-phenylalanyl-tRNA].", "content": "N-Chlorambucilyl-[14C]phenylalanyl-tRNA was used for the affinity modification of phenylalanine : tRNA-ligase from E. coli MRE-600. It has been found that N-chlorambucilyl-[14C]phenylalanyl-tRNA selectively inactivates phenylalanine : tRNA-lagase that results in formation of a covalent bond between the tRNA derivative and the enzyme at pH 5.8, 25 degrees C. The rate fall of the aminoacylation of tRNA with [14C]phenylalanine was observed after the enzyme incubation with N-chlorambucilyl-[14C]phenylalanyl-tRNA at pH 7.5, 25 degrees C. It has been shown that this modification results in a similar rate decrease of tRNA aminoacylation with [14C]phenylalanine, ATP-[32P]pyrophosphate exchange and reaction of the enzymatic deacylation of [14C]phenylalanyl-tRNA. This fact evidences in favour of the possibility of the alkylation to proceed in the proximity of the active centre of the enzyme. The covalent complex obtained seems to be an interesting model for the studies of the mechanisms involved in tRNA aminoacylation as well as for elucidation of the tertiary structure of tRNA bound with the enzyme.", "contents": "[Specific modification of phenylalanine:tRNA-ligases of E. coli MRE-600 with N-chlorambucilyl-14c-phenylalanyl-tRNA]. N-Chlorambucilyl-[14C]phenylalanyl-tRNA was used for the affinity modification of phenylalanine : tRNA-ligase from E. coli MRE-600. It has been found that N-chlorambucilyl-[14C]phenylalanyl-tRNA selectively inactivates phenylalanine : tRNA-lagase that results in formation of a covalent bond between the tRNA derivative and the enzyme at pH 5.8, 25 degrees C. The rate fall of the aminoacylation of tRNA with [14C]phenylalanine was observed after the enzyme incubation with N-chlorambucilyl-[14C]phenylalanyl-tRNA at pH 7.5, 25 degrees C. It has been shown that this modification results in a similar rate decrease of tRNA aminoacylation with [14C]phenylalanine, ATP-[32P]pyrophosphate exchange and reaction of the enzymatic deacylation of [14C]phenylalanyl-tRNA. This fact evidences in favour of the possibility of the alkylation to proceed in the proximity of the active centre of the enzyme. The covalent complex obtained seems to be an interesting model for the studies of the mechanisms involved in tRNA aminoacylation as well as for elucidation of the tertiary structure of tRNA bound with the enzyme."} {"id": "PMID:175269", "title": "Studies on chemically induced dominant lethality. I. The cytogenetic basis of MMS-induced dominant lethality in post-meiotic male germ cells.", "content": "Young adult male mice were injected intravenously with doses of methyl methanesulfonate(MMS) ranging from 25 to 100 mg/kg body weight. These males were serially mated to superovulated females from day 1 post injection to day 23 post injection. The morning after mating (about 4-6 h post-copulation) the females were sacrificed and ova flushed from the ampulla. The ova were cultured, in the presence of colchicine, for 26 h and metaphase preparations made of the first cleavage division. Chromosome analysis was done and the types, and extent, of chromosome aberrations correlated to previously published dominant lethal data at the same MMS doses and time intervals. The types of aberrations seen were predominantly double fragments (presumably isochromatid deletions), chromatid interchanges, and some chromatid deletions, as well as shattering effect on the male complement at the highest dose and the time of peak sensitivity to dominant lethal induction. When the frequency of cells containing a cytologically visible aberration is compared to the total dominant lethal data an excellent correlation is obtained. Furthermore, the frequency of highly damaged cells, agrees very well with estimated frequencies of preimplantation loss. These data strongly suggest that chromosome aberrations seen at the first cleavage stage are the basis of MMS-induced dominant lethality.", "contents": "Studies on chemically induced dominant lethality. I. The cytogenetic basis of MMS-induced dominant lethality in post-meiotic male germ cells. Young adult male mice were injected intravenously with doses of methyl methanesulfonate(MMS) ranging from 25 to 100 mg/kg body weight. These males were serially mated to superovulated females from day 1 post injection to day 23 post injection. The morning after mating (about 4-6 h post-copulation) the females were sacrificed and ova flushed from the ampulla. The ova were cultured, in the presence of colchicine, for 26 h and metaphase preparations made of the first cleavage division. Chromosome analysis was done and the types, and extent, of chromosome aberrations correlated to previously published dominant lethal data at the same MMS doses and time intervals. The types of aberrations seen were predominantly double fragments (presumably isochromatid deletions), chromatid interchanges, and some chromatid deletions, as well as shattering effect on the male complement at the highest dose and the time of peak sensitivity to dominant lethal induction. When the frequency of cells containing a cytologically visible aberration is compared to the total dominant lethal data an excellent correlation is obtained. Furthermore, the frequency of highly damaged cells, agrees very well with estimated frequencies of preimplantation loss. These data strongly suggest that chromosome aberrations seen at the first cleavage stage are the basis of MMS-induced dominant lethality."} {"id": "PMID:175265", "title": "[MS2 RNA hydrolysis by snake venom phosphodiesterase and template properties of RNA produced by limited exonucleolytic action].", "content": "The action of snake venom phosphodiesterase on bacteriophage MS2 RNA under conditions of limited hydrolysis has been studied. The content of 5'-mononucleotides released during hydrolysis does not correspond to the calculated one based on the 3'-terminal nucleotide sequence of MS2 RNA. This finding suggests the occurrence of endonucleolytic splits in MS2 RNA with concomitant exonucleolytic digestion of some newly formed fragments. A high molecular weight RNA fraction, comprising unfragmented MS2 RNA with about 5-63'-terminal nucleotides removed is separated by sucrose gradient centrifugation and shown not to differ from the native MS2 RNA in its template function in a cell-free protein synthesizing system. It is demonstrated that template activity, polarity of translation, and nascent peptide chain termination on the MS2 replicase cistron are not affected by the removal of 3'terminal nucleotides of MS2 RNA. Consequently, these nucleotides are unessential in translation of native MS2 RNA.", "contents": "[MS2 RNA hydrolysis by snake venom phosphodiesterase and template properties of RNA produced by limited exonucleolytic action]. The action of snake venom phosphodiesterase on bacteriophage MS2 RNA under conditions of limited hydrolysis has been studied. The content of 5'-mononucleotides released during hydrolysis does not correspond to the calculated one based on the 3'-terminal nucleotide sequence of MS2 RNA. This finding suggests the occurrence of endonucleolytic splits in MS2 RNA with concomitant exonucleolytic digestion of some newly formed fragments. A high molecular weight RNA fraction, comprising unfragmented MS2 RNA with about 5-63'-terminal nucleotides removed is separated by sucrose gradient centrifugation and shown not to differ from the native MS2 RNA in its template function in a cell-free protein synthesizing system. It is demonstrated that template activity, polarity of translation, and nascent peptide chain termination on the MS2 replicase cistron are not affected by the removal of 3'terminal nucleotides of MS2 RNA. Consequently, these nucleotides are unessential in translation of native MS2 RNA."} {"id": "PMID:175270", "title": "Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells and zygotes of mice. II. Sensitivity of different postcopulation-precleavage stages to three alkylating chemicals.", "content": "The relative sensitivities of various postcopulation-precleabage and pronuclear stages to dominant-lethal effects of isopropyl methanesulfonate (IMS), ethyl methanesulfonate (EMS), and triethylenemelamine (TEM) were investigated. The pattern of sensitivity differed with the chemical. IMS was most effective when pronuclear formation was already completed and the majority of the zygotes were presumably undergoing DNA synthesis. EMS, on the other hand, induced its most pronounced effects when eggs in the course of second meiotic division and zygotes in early pronuclear stages were treated. The greatest effect of TEM was observed when zygotes were treated at the early pronuclear stage. EMS and TEM, in contrast to IMS, are similar to radiations in that zygotes undergoing DNA synthesis are more resistant to them than are the early pronuclear stages. In the case of IMS, effects induced in the most sensitive postcopulation-precleavage stage were 6 to 9 times greater than in the most sensitive precopulatory dictyate oocytes or male germ cells. On the other hand, in the case of EMS and TEM, the most sensitive precopulatory male germ cells, but not the dictyate oocytes, were more sensitive than the most sensitive postcopulation stages.", "contents": "Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells and zygotes of mice. II. Sensitivity of different postcopulation-precleavage stages to three alkylating chemicals. The relative sensitivities of various postcopulation-precleabage and pronuclear stages to dominant-lethal effects of isopropyl methanesulfonate (IMS), ethyl methanesulfonate (EMS), and triethylenemelamine (TEM) were investigated. The pattern of sensitivity differed with the chemical. IMS was most effective when pronuclear formation was already completed and the majority of the zygotes were presumably undergoing DNA synthesis. EMS, on the other hand, induced its most pronounced effects when eggs in the course of second meiotic division and zygotes in early pronuclear stages were treated. The greatest effect of TEM was observed when zygotes were treated at the early pronuclear stage. EMS and TEM, in contrast to IMS, are similar to radiations in that zygotes undergoing DNA synthesis are more resistant to them than are the early pronuclear stages. In the case of IMS, effects induced in the most sensitive postcopulation-precleavage stage were 6 to 9 times greater than in the most sensitive precopulatory dictyate oocytes or male germ cells. On the other hand, in the case of EMS and TEM, the most sensitive precopulatory male germ cells, but not the dictyate oocytes, were more sensitive than the most sensitive postcopulation stages."} {"id": "PMID:175271", "title": "Inadequate parathyroid response in acute pancreatitis.", "content": "We studied nine consecutive hypocalcemic patients with acute pancreatitis to elucidate the mechanism of hypocalcemia. Mean serum ionized calcium, 0.97 mM, was below the normal mean of 1.16 mM (P less than 0.001). Seven of eight patients tested had normal parathyroid hormone levels. All responded to parenteral parathyroid extract by increasing serum ionized calcium and urinary cyclic AMP, indicating parathyroid-hormone-responsive target organs. Calcitonin and glucagon concentrations were increased above normal in some patients, but there was no relation with serum ionized calcium. Parenteral glucagon had no significant effect on serum ionized calcium or calcitonin concentrations. These findings suggest that neither glucagon nor calcitonin was primarily responsible for the hypocalcemia, which did not produce expected increases in serum parathyroid hormone concentrations. Relative parathyroid insufficiency may account for the persistent hypocalcemia frequently observed in patients with acute pancreatitis.", "contents": "Inadequate parathyroid response in acute pancreatitis. We studied nine consecutive hypocalcemic patients with acute pancreatitis to elucidate the mechanism of hypocalcemia. Mean serum ionized calcium, 0.97 mM, was below the normal mean of 1.16 mM (P less than 0.001). Seven of eight patients tested had normal parathyroid hormone levels. All responded to parenteral parathyroid extract by increasing serum ionized calcium and urinary cyclic AMP, indicating parathyroid-hormone-responsive target organs. Calcitonin and glucagon concentrations were increased above normal in some patients, but there was no relation with serum ionized calcium. Parenteral glucagon had no significant effect on serum ionized calcium or calcitonin concentrations. These findings suggest that neither glucagon nor calcitonin was primarily responsible for the hypocalcemia, which did not produce expected increases in serum parathyroid hormone concentrations. Relative parathyroid insufficiency may account for the persistent hypocalcemia frequently observed in patients with acute pancreatitis."} {"id": "PMID:175276", "title": "Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome.", "content": "Since Reye's syndrome is associated with hyperammonemia, we measured the urea-cycle enzymes in hepatic tissue of 13 patients. Expressed as nanomoles of citrulline per milligram of hepatic protein per minute, mean activity of carbamyl phosphate synthetase (6.27 +/- 2.45 S.D.) and ornithine transcarbamylase (136.19 +/- 41.83) in Reye's syndrome was reduced significantly (P less than 0.005) when compared with that of 25 \"normal\" controls (11.54 +/- 4.24 and 307.49 +/- 94.15, respectively). Activity was maximally reduced during the first days of clinical symptoms; it returned toward normal during the following week regardless of whether the disease ended in death or recovery. The activity of the two enzymes was normal in patients with salicylate intoxication or heritable argininosuccinic acid synthetase deficiency. The apparent Km of hepatic ornithine transcarbamylase for ornithine was in the normal range in patients with Reye's syndrome (mean 0.24 mM). These observations indicate that Reye's syndrome is associated with acquired and transient dysfunction of hepatic mitochondrial urea-cycle enzymes.", "contents": "Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome. Since Reye's syndrome is associated with hyperammonemia, we measured the urea-cycle enzymes in hepatic tissue of 13 patients. Expressed as nanomoles of citrulline per milligram of hepatic protein per minute, mean activity of carbamyl phosphate synthetase (6.27 +/- 2.45 S.D.) and ornithine transcarbamylase (136.19 +/- 41.83) in Reye's syndrome was reduced significantly (P less than 0.005) when compared with that of 25 \"normal\" controls (11.54 +/- 4.24 and 307.49 +/- 94.15, respectively). Activity was maximally reduced during the first days of clinical symptoms; it returned toward normal during the following week regardless of whether the disease ended in death or recovery. The activity of the two enzymes was normal in patients with salicylate intoxication or heritable argininosuccinic acid synthetase deficiency. The apparent Km of hepatic ornithine transcarbamylase for ornithine was in the normal range in patients with Reye's syndrome (mean 0.24 mM). These observations indicate that Reye's syndrome is associated with acquired and transient dysfunction of hepatic mitochondrial urea-cycle enzymes."} {"id": "PMID:175286", "title": "Receptor-binding region of insulin.", "content": "X-ray analysis, circular dichroism, receptor binding and biological potencies of chemically modified insulins suggest that the conformation of the insulin molecule is critical to the formation of both the zinc insulin hexamer and the insulin-receptor complex. Results are consistent with an insulin receptor-binding region including many of the hydrophobic residues important to dimerisation in addition to more polar surface residues. There is a further possibility of formation of an antiparallel sheet structure between the insulin and receptor molecules in the complex similar to that between monomers in the insulin dimer.", "contents": "Receptor-binding region of insulin. X-ray analysis, circular dichroism, receptor binding and biological potencies of chemically modified insulins suggest that the conformation of the insulin molecule is critical to the formation of both the zinc insulin hexamer and the insulin-receptor complex. Results are consistent with an insulin receptor-binding region including many of the hydrophobic residues important to dimerisation in addition to more polar surface residues. There is a further possibility of formation of an antiparallel sheet structure between the insulin and receptor molecules in the complex similar to that between monomers in the insulin dimer."} {"id": "PMID:175297", "title": "[Topochemistry of hormone action].", "content": "The site of hormone action is the cells of target tissues. Now that ultrastructural research has revealed the complexity of eukaryotic cells, we must ask which cellular structures are involved. Some hormones act at the cell membrane, mainly via adenylate cyclase and the \"second messenger\" cAMP. The cytosol and the mitochondria, the main sites of intermediate metabolism and enzyme activity, are apparently not involved, although in the past interaction of hormones with enzymes has been postulated. Most of the steroid hormones act at the level of the cell nucleus, regulating transcription of specific genes and inducing enzymes or other proteins. The mechanisms by means of which this regulation is achieved are not fully understood, but it is likely that derepression is involved. The active agent seems to be a complex of the hormone with a receptor protein.", "contents": "[Topochemistry of hormone action]. The site of hormone action is the cells of target tissues. Now that ultrastructural research has revealed the complexity of eukaryotic cells, we must ask which cellular structures are involved. Some hormones act at the cell membrane, mainly via adenylate cyclase and the \"second messenger\" cAMP. The cytosol and the mitochondria, the main sites of intermediate metabolism and enzyme activity, are apparently not involved, although in the past interaction of hormones with enzymes has been postulated. Most of the steroid hormones act at the level of the cell nucleus, regulating transcription of specific genes and inducing enzymes or other proteins. The mechanisms by means of which this regulation is achieved are not fully understood, but it is likely that derepression is involved. The active agent seems to be a complex of the hormone with a receptor protein."} {"id": "PMID:175302", "title": "Neoplastic transformation of mouse embryo cells by virus released from tumorigenic mouse cells transformed by avian sarcoma virus B77.", "content": "Mouse C3H embryo cells were transformed in vitro by avian sarcoma virus Bratislava 77 (B77) released scantily from a mouse cell line transformed earlier by the same virus. B77 virus transformed C3H embryo cells contained B77 viral genome and were transplantable into syngeneic as well as allogeneic DBA/2J young mice in which autochthonous sarcomas were induced. Tumors in both strains of mice were virogenic. The probable reasons for an increased transformation capacity of B77 virus in mammals are discussed.", "contents": "Neoplastic transformation of mouse embryo cells by virus released from tumorigenic mouse cells transformed by avian sarcoma virus B77. Mouse C3H embryo cells were transformed in vitro by avian sarcoma virus Bratislava 77 (B77) released scantily from a mouse cell line transformed earlier by the same virus. B77 virus transformed C3H embryo cells contained B77 viral genome and were transplantable into syngeneic as well as allogeneic DBA/2J young mice in which autochthonous sarcomas were induced. Tumors in both strains of mice were virogenic. The probable reasons for an increased transformation capacity of B77 virus in mammals are discussed."} {"id": "PMID:175303", "title": "Viruses harboured in blasts of the rat myelogenous leukemia (RBA-Le), induced by chicken sarcoma virus.", "content": "It was shown that the rat myelogenous leukemia RBA-Le harbours three kinds of viruses. 1. Rat leukemogenic virus, which can be recovered from leukemic cells, medium of cultured leukemic cells and the plasma of leukemic rats. About 12% of rats inoculated when newborn with the recovered virus developed leukemia. 2. Chicken sarcoma virus, which seems to have a lowered infectivity or altered host range as the B77(RBI) virus by which this leukemia had been induced. 3. A cytopathic, hemagglutinating virus, very pathogenic for baby rats, which was shown to be closely related, if not identical in biological as well as immunological properties with Kilham rat virus. The RBA-Le leukemic cells were adapted for growth in tissue culture.", "contents": "Viruses harboured in blasts of the rat myelogenous leukemia (RBA-Le), induced by chicken sarcoma virus. It was shown that the rat myelogenous leukemia RBA-Le harbours three kinds of viruses. 1. Rat leukemogenic virus, which can be recovered from leukemic cells, medium of cultured leukemic cells and the plasma of leukemic rats. About 12% of rats inoculated when newborn with the recovered virus developed leukemia. 2. Chicken sarcoma virus, which seems to have a lowered infectivity or altered host range as the B77(RBI) virus by which this leukemia had been induced. 3. A cytopathic, hemagglutinating virus, very pathogenic for baby rats, which was shown to be closely related, if not identical in biological as well as immunological properties with Kilham rat virus. The RBA-Le leukemic cells were adapted for growth in tissue culture."} {"id": "PMID:175308", "title": "Virus infections and acute renal transplant rejection.", "content": "The date of onset of 360 acute renal transplant rejection episodes from 1969 to 1973 have been compared with the prevalence of various common viral infections and infections due to Mycoplasma pnuemoniae. A positive correlation was found for influenza B infections (r=0.43, p less than 0.01) up to 5 months before transplantation and for adenovirus infections (r=0.32, p less than 0.05) at 1 month before kidney grafting.", "contents": "Virus infections and acute renal transplant rejection. The date of onset of 360 acute renal transplant rejection episodes from 1969 to 1973 have been compared with the prevalence of various common viral infections and infections due to Mycoplasma pnuemoniae. A positive correlation was found for influenza B infections (r=0.43, p less than 0.01) up to 5 months before transplantation and for adenovirus infections (r=0.32, p less than 0.05) at 1 month before kidney grafting."} {"id": "PMID:175312", "title": "Glucocorticoid binding to adenohypophysis receptors and its physiological role.", "content": "The binding characteristics of glucocorticoids to cytoplasmic and nuclear fractions of the adenohypophysis were determined and an attempt was made to correlate steroid uptake with physiological action. Binding was of high affinity and exhibited a limited number of acceptor sites for dexamethasone (Dx). It was shown that the steroid-receptor complex dissociated rapidly at 37 degree C, but was stable at low temperatures. An inverse relationship was detected between the plasma corticosterone (B) titer and the capacity of receptors to combine 3h-Dx. Shortly after stress or injection of physiological doses of B,50 to 70% of the acceptor sites were saturated. Progressive desaturation of the occupied receptors appeared to depend upon time and the plasma B concentration. Some evidence was also provided supporting a possible correlation between the extent of Dx inhibition of in vitro ACTH secretion and the degree of binding sites' occupancy. These results suggest that glucocorticoid binding to pituitary receptors may be correlated with the physiological action of the steroids on ACTH release.", "contents": "Glucocorticoid binding to adenohypophysis receptors and its physiological role. The binding characteristics of glucocorticoids to cytoplasmic and nuclear fractions of the adenohypophysis were determined and an attempt was made to correlate steroid uptake with physiological action. Binding was of high affinity and exhibited a limited number of acceptor sites for dexamethasone (Dx). It was shown that the steroid-receptor complex dissociated rapidly at 37 degree C, but was stable at low temperatures. An inverse relationship was detected between the plasma corticosterone (B) titer and the capacity of receptors to combine 3h-Dx. Shortly after stress or injection of physiological doses of B,50 to 70% of the acceptor sites were saturated. Progressive desaturation of the occupied receptors appeared to depend upon time and the plasma B concentration. Some evidence was also provided supporting a possible correlation between the extent of Dx inhibition of in vitro ACTH secretion and the degree of binding sites' occupancy. These results suggest that glucocorticoid binding to pituitary receptors may be correlated with the physiological action of the steroids on ACTH release."} {"id": "PMID:175313", "title": "Subcortical pathways involved in the mediation of andrenocortical responses following sciatic nerve stimulation.", "content": "Previous experiments from this laboratory using the hypothalamic island have demonstrated that the adrenocortical discharge following sciatic nerve stimulation is mediated by neural pathways only. With the purpose of identifying the neural structures involved, this response was studied in rats with bilateral lesions in the medial forebrain bundle (MFB), mammillary peduncle (MP), fasciculus longitudinalis dorsalis (FLD), midbrain reticular formation MRF) and the medial geniculate body (GM). Lesions in the MFB, MP and MRF have inhibited the adrenocortical response following sciatic nerve stimulation. These and other data indicate that the above structures are involved in the mediation of this response and that the afferent pathway enters the mediobasal hypothalamus anteriorly.", "contents": "Subcortical pathways involved in the mediation of andrenocortical responses following sciatic nerve stimulation. Previous experiments from this laboratory using the hypothalamic island have demonstrated that the adrenocortical discharge following sciatic nerve stimulation is mediated by neural pathways only. With the purpose of identifying the neural structures involved, this response was studied in rats with bilateral lesions in the medial forebrain bundle (MFB), mammillary peduncle (MP), fasciculus longitudinalis dorsalis (FLD), midbrain reticular formation MRF) and the medial geniculate body (GM). Lesions in the MFB, MP and MRF have inhibited the adrenocortical response following sciatic nerve stimulation. These and other data indicate that the above structures are involved in the mediation of this response and that the afferent pathway enters the mediobasal hypothalamus anteriorly."} {"id": "PMID:175314", "title": "The use of steroids in the treatment of idiopathic polyneuritis.", "content": "The efficacy of steroids in the treatment of acute idiopathic polyneuritis (Guillain-Barr\u00e9 syndrome) continues to be uncertain. Since 1965, 38 patients with idiopathic polyneuritis have been at the University of Kentucky Medical Center, and 16 of them were entered in a prospective double blind study designed to assess the effectiveness of steroid therapy. Seriously ill patients were excluded from the study and most of them received steroids. In both the double-blind group and the entire group of patients, the time from the onset of illness to recovery was significantly less in patients treated with steroids, although steroids did not alter the initial severity of illness or the duration of hospitalization.", "contents": "The use of steroids in the treatment of idiopathic polyneuritis. The efficacy of steroids in the treatment of acute idiopathic polyneuritis (Guillain-Barr\u00e9 syndrome) continues to be uncertain. Since 1965, 38 patients with idiopathic polyneuritis have been at the University of Kentucky Medical Center, and 16 of them were entered in a prospective double blind study designed to assess the effectiveness of steroid therapy. Seriously ill patients were excluded from the study and most of them received steroids. In both the double-blind group and the entire group of patients, the time from the onset of illness to recovery was significantly less in patients treated with steroids, although steroids did not alter the initial severity of illness or the duration of hospitalization."} {"id": "PMID:175315", "title": "Glue sniffer's neuropathy.", "content": "Progressive sensorimotor neuropathy developed in two patients exposed to prolonged (chronic) inhalation of n-hexane (glue sniffing). Sural nerve biopsies showed loss of axons; remaining axons were either normal or showed accumulation of filaments of 90 to 100 A thick, widened nodes of Ranvier, and focal enlargements. The muscle biopsy revealed neurogenic atrophy. Intramuscular nerve twigs and end-plates, studied in one patient, showed loss of axons and nerve terminals. Unmyelinated axons also showed accululation of 60 to 100 A thick filaments. The similarities between the pathologic findings in the peripheral nerve of these patients and those with acrylamide neuropathy suggest that the n-hexane inhalation produces a dying back neuropathy.", "contents": "Glue sniffer's neuropathy. Progressive sensorimotor neuropathy developed in two patients exposed to prolonged (chronic) inhalation of n-hexane (glue sniffing). Sural nerve biopsies showed loss of axons; remaining axons were either normal or showed accumulation of filaments of 90 to 100 A thick, widened nodes of Ranvier, and focal enlargements. The muscle biopsy revealed neurogenic atrophy. Intramuscular nerve twigs and end-plates, studied in one patient, showed loss of axons and nerve terminals. Unmyelinated axons also showed accululation of 60 to 100 A thick filaments. The similarities between the pathologic findings in the peripheral nerve of these patients and those with acrylamide neuropathy suggest that the n-hexane inhalation produces a dying back neuropathy."} {"id": "PMID:175321", "title": "Initiation of labor by intraamniotic cortisol instillation in prolonged human pregnancy.", "content": "The fetal adrenal cortex has recently been implicated in the etiology of postmaturity on the basis of low cortisol levels found in the plasma of postmature neonates. These findings suggested that labor could be initiated in prolonged pregnancy by iatrogenic elevation of fetal plasma cortisol. In the current investigation designed to test this hypothesis, 500 mg of hydrocortisone sodium succinate, dissolved in the accompanying diluent of bacteriostatic water to form 4 ml of solution, was injected intraamniotically in 10 patients with unfavorable cervices who were 12 or more days past their expected date of confinement. Nine similar patients serving as controls received 4 ml of bacteriostatic water intraamniotically. All patients were followed with daily determinations of urinary estriol. Eight of the 10 patients who received cortisol went into labor within 120 hours of instillation, as compared with 2 of the 9 patients in the control group. Comparison of the two groups revealed a significant difference (p less than 0.01). The mean instillation-labor time for the cortisol group was 86 hours compared with 228 hours in the control group. This difference was also significant (p less than 0.001). Urinary estriol excretion declined sequentially following cortisol but not after infusion of water. These findings are consistent with the hypotheses that a) spontaneous labor in the human may be preceded by a sudden rise in fetal plasma cortisol, as in the sheep; b) the fetal pituitary-hypothalamic axis is responsive to cortisol, hence the falling estriol excretion; and c) ACTH may be the tropic hormone for the provisional zone of the fetal adrenal cortex.", "contents": "Initiation of labor by intraamniotic cortisol instillation in prolonged human pregnancy. The fetal adrenal cortex has recently been implicated in the etiology of postmaturity on the basis of low cortisol levels found in the plasma of postmature neonates. These findings suggested that labor could be initiated in prolonged pregnancy by iatrogenic elevation of fetal plasma cortisol. In the current investigation designed to test this hypothesis, 500 mg of hydrocortisone sodium succinate, dissolved in the accompanying diluent of bacteriostatic water to form 4 ml of solution, was injected intraamniotically in 10 patients with unfavorable cervices who were 12 or more days past their expected date of confinement. Nine similar patients serving as controls received 4 ml of bacteriostatic water intraamniotically. All patients were followed with daily determinations of urinary estriol. Eight of the 10 patients who received cortisol went into labor within 120 hours of instillation, as compared with 2 of the 9 patients in the control group. Comparison of the two groups revealed a significant difference (p less than 0.01). The mean instillation-labor time for the cortisol group was 86 hours compared with 228 hours in the control group. This difference was also significant (p less than 0.001). Urinary estriol excretion declined sequentially following cortisol but not after infusion of water. These findings are consistent with the hypotheses that a) spontaneous labor in the human may be preceded by a sudden rise in fetal plasma cortisol, as in the sheep; b) the fetal pituitary-hypothalamic axis is responsive to cortisol, hence the falling estriol excretion; and c) ACTH may be the tropic hormone for the provisional zone of the fetal adrenal cortex."} {"id": "PMID:175322", "title": "Hydatidiform mole: a vascular congenital anomaly.", "content": "The thesis is advanced that a critical time for development of embryonic blood vessels in the placenta is 13 to 21 days after conception, especially during days 18 to 21. Dietary requirements at this time are specific and demanding for nutritional precursors of thymidine which is an important constituent of DNA. Folic acid and histidine are specifically essential for thymidine synthesis. These are reviewed with respect to cultures and socioeconomon levels in societies where occurrence of hydatidiform mole is endemic. Specific nutritional deficiencies are discussed in relation to kinds of diets and ways of food preparation. When specific dietary requirements are lacking at a time of high need, embryo death, abnormality, and/or avascularity of trophoblastic placental villi may be the earliest pathogenic signs of hydatidiform mole.", "contents": "Hydatidiform mole: a vascular congenital anomaly. The thesis is advanced that a critical time for development of embryonic blood vessels in the placenta is 13 to 21 days after conception, especially during days 18 to 21. Dietary requirements at this time are specific and demanding for nutritional precursors of thymidine which is an important constituent of DNA. Folic acid and histidine are specifically essential for thymidine synthesis. These are reviewed with respect to cultures and socioeconomon levels in societies where occurrence of hydatidiform mole is endemic. Specific nutritional deficiencies are discussed in relation to kinds of diets and ways of food preparation. When specific dietary requirements are lacking at a time of high need, embryo death, abnormality, and/or avascularity of trophoblastic placental villi may be the earliest pathogenic signs of hydatidiform mole."} {"id": "PMID:175324", "title": "Pulsatile gonadotropin output in menstrual dysfunction.", "content": "Patterns of gonadotorpin output were studied in normal individuals and in patients with menstrual dysfunction by radioimmunoassay measurement of LH and FSH output in samples taken every 20 minutes for 6-8 hours, and following administration of synthetic luteinizing hormone releasing hormone (LRH). Follicular phase LH pulses occurred every 1-2 hours, whereas those in the luteal phase occurred less frequently and with higher amplitude. FSH output was irregular, and had no correlation with LH dynamics. In anorixia nervosa, pulsatile LH activity was minimal, and the response to LRH variable, correlating somewhat with the clinical status of the patient. Pulsatile LH activity was observed in patients with postpill and postpartum amenorrhea, and also in one individual with a probable prolactin-producing pituitary tumor. Patients with polycystic ovarian disease had obvious LH pulsatile activity, with a greater amplitude and frequency than seen in the luteal phase, and a decrease in percentage increment, suggesting some difference in the hypothalamic-pituitary control mechanisms under these conditions. The character and pattern of the LH pulsatile activity does vary with different forms of menstrual dysfunction and may be predictive of the LRH response when considered in relation to the LH baseline values. Pulsatile LH activity, analyzed in conjunction with response patterns following LRH stimulation, may reflect the degree of hypothalamic dysfunction.", "contents": "Pulsatile gonadotropin output in menstrual dysfunction. Patterns of gonadotorpin output were studied in normal individuals and in patients with menstrual dysfunction by radioimmunoassay measurement of LH and FSH output in samples taken every 20 minutes for 6-8 hours, and following administration of synthetic luteinizing hormone releasing hormone (LRH). Follicular phase LH pulses occurred every 1-2 hours, whereas those in the luteal phase occurred less frequently and with higher amplitude. FSH output was irregular, and had no correlation with LH dynamics. In anorixia nervosa, pulsatile LH activity was minimal, and the response to LRH variable, correlating somewhat with the clinical status of the patient. Pulsatile LH activity was observed in patients with postpill and postpartum amenorrhea, and also in one individual with a probable prolactin-producing pituitary tumor. Patients with polycystic ovarian disease had obvious LH pulsatile activity, with a greater amplitude and frequency than seen in the luteal phase, and a decrease in percentage increment, suggesting some difference in the hypothalamic-pituitary control mechanisms under these conditions. The character and pattern of the LH pulsatile activity does vary with different forms of menstrual dysfunction and may be predictive of the LRH response when considered in relation to the LH baseline values. Pulsatile LH activity, analyzed in conjunction with response patterns following LRH stimulation, may reflect the degree of hypothalamic dysfunction."} {"id": "PMID:175325", "title": "Insulinoma in a pregnant woman.", "content": "The case of a 37-year-old primigravida suffering from severe hypoglycemia due to insulinoma is reported. Diagnosis was established on clinical grounds by assessment of inappropriate insulin release. Laparotomy was performed by the 12th gestational week. A wide distal pancreatectomy was carried out, and histopathologic study proved the existence of multiple islet cell adenomatosis. Glycemic levels and insulin secretion returned to normal immediately after surgery. The course of pregnancy was unhampered, judged by clinical criteria and by serial estimations of human chorionic somatomammotropin levels before and after removal of the insulin-producing tumor. A normal female infant was delivered at term, and no histopatholgic changes were detected in the placenta. After 1 year, clinical and analytical evaluation of both mother and child was normal.", "contents": "Insulinoma in a pregnant woman. The case of a 37-year-old primigravida suffering from severe hypoglycemia due to insulinoma is reported. Diagnosis was established on clinical grounds by assessment of inappropriate insulin release. Laparotomy was performed by the 12th gestational week. A wide distal pancreatectomy was carried out, and histopathologic study proved the existence of multiple islet cell adenomatosis. Glycemic levels and insulin secretion returned to normal immediately after surgery. The course of pregnancy was unhampered, judged by clinical criteria and by serial estimations of human chorionic somatomammotropin levels before and after removal of the insulin-producing tumor. A normal female infant was delivered at term, and no histopatholgic changes were detected in the placenta. After 1 year, clinical and analytical evaluation of both mother and child was normal."} {"id": "PMID:175326", "title": "Ergonomics study shows effect of full-body suit on energy use.", "content": "It stands to reason that a full-body protective suit has an impact on the worker's body. It has weight, it does restrict movement to an extent. It's not like wearing a sport shirt. But, how much of an impact and what kind; how much of an energy drain is it? This ergonomic study addresses itself to the energy expenditure from wearing such a suit. The study reveals that the energy requirements in workers undergoing light to moderate exercise do increase. In some cases, the increase may be marked, with the physiological work level going from light to moderate to heavy. This work-level jump isn't always detectable by monitoring pulse rate alone. It's also reflected by an increase in minute ventilation and oxygen consumption. One tentative conclusion coming from this study is the possibility of improving comfort and reducing the energy requirements of workers using such equipment by increasing the volume of air supplied to the suit.", "contents": "Ergonomics study shows effect of full-body suit on energy use. It stands to reason that a full-body protective suit has an impact on the worker's body. It has weight, it does restrict movement to an extent. It's not like wearing a sport shirt. But, how much of an impact and what kind; how much of an energy drain is it? This ergonomic study addresses itself to the energy expenditure from wearing such a suit. The study reveals that the energy requirements in workers undergoing light to moderate exercise do increase. In some cases, the increase may be marked, with the physiological work level going from light to moderate to heavy. This work-level jump isn't always detectable by monitoring pulse rate alone. It's also reflected by an increase in minute ventilation and oxygen consumption. One tentative conclusion coming from this study is the possibility of improving comfort and reducing the energy requirements of workers using such equipment by increasing the volume of air supplied to the suit."} {"id": "PMID:175338", "title": "[Oxygen consumption and cytochrome oxidase activity of muscle tissue from the limbs of axolotls following restoration of regenerative capability suppressed by x-ray irradiation].", "content": "The intensity of oxygen consumption and the activity of cytochrome oxidase have been studied in the homogenate, mitochondria and nuclei of the limb muscle tissue in axolotls after the suppression of regenerative ability by X-irradiation and its experimental restoration. Under the suppression of regenerative ability, the oxygen consumption was inhibited. The cytochrome oxidase activity in the homogenate and mitochondria decreased and in the nuclei remained at the same level or even increased as compared with the intact limb. Under the restoration of regenerative ability, the intensity of respiration of the homogenate and mitochondria increased and this increase was accompanied by the increase of the cytochrome oxidase activity. The activity of cytochrome oxidase in the nuclei did not change at the stage of blastema and sharply fell at the stage of formed limb.", "contents": "[Oxygen consumption and cytochrome oxidase activity of muscle tissue from the limbs of axolotls following restoration of regenerative capability suppressed by x-ray irradiation]. The intensity of oxygen consumption and the activity of cytochrome oxidase have been studied in the homogenate, mitochondria and nuclei of the limb muscle tissue in axolotls after the suppression of regenerative ability by X-irradiation and its experimental restoration. Under the suppression of regenerative ability, the oxygen consumption was inhibited. The cytochrome oxidase activity in the homogenate and mitochondria decreased and in the nuclei remained at the same level or even increased as compared with the intact limb. Under the restoration of regenerative ability, the intensity of respiration of the homogenate and mitochondria increased and this increase was accompanied by the increase of the cytochrome oxidase activity. The activity of cytochrome oxidase in the nuclei did not change at the stage of blastema and sharply fell at the stage of formed limb."} {"id": "PMID:175341", "title": "[Pyridoxal phosphate and activity of pyridoxalkinase in serum of preterm and term infants (author's transl)].", "content": "Vitamin B6 nutriture was measured in 14 preterm infants (born between 30th and 35th week of gestation) by means of determination of pyridoxalphosphate and activity of pyridoxalkinase in serum on the 1st and 4th day of life. 11 term infants were included as control group. At the 1st day pyridoxalphosphate and activity of pyridoxalkinase in preterm infants were significantly decreased in comparison with the control group. 50% of preterm infants--all were delivered before the 33rd week of pregnancy--did not show any activity of pyridoxalkinase in serum. On the 4th day, vitamin B6 nutriture of preterm infants was still decreased in comparison with the control group. Measurable activity of pyridoxalkinase, however, was now found in all preterm infants. There was a positive correlation at the 1st and 4th day of life between pyridoxalphosphate and weight and activity of pyridoxalkinase and weight. According to our results pyridoxalkinase is an enzyme which depends on the gestational age of the newborn. After the 32nd week of gestation the enzyme becomes active. Moreover pyridoxalkinase is an enzyme that can be induced by formulas containing vitamin B6. We consider the administration of vitamin B6 to the preterm infant as necessary.", "contents": "[Pyridoxal phosphate and activity of pyridoxalkinase in serum of preterm and term infants (author's transl)]. Vitamin B6 nutriture was measured in 14 preterm infants (born between 30th and 35th week of gestation) by means of determination of pyridoxalphosphate and activity of pyridoxalkinase in serum on the 1st and 4th day of life. 11 term infants were included as control group. At the 1st day pyridoxalphosphate and activity of pyridoxalkinase in preterm infants were significantly decreased in comparison with the control group. 50% of preterm infants--all were delivered before the 33rd week of pregnancy--did not show any activity of pyridoxalkinase in serum. On the 4th day, vitamin B6 nutriture of preterm infants was still decreased in comparison with the control group. Measurable activity of pyridoxalkinase, however, was now found in all preterm infants. There was a positive correlation at the 1st and 4th day of life between pyridoxalphosphate and weight and activity of pyridoxalkinase and weight. According to our results pyridoxalkinase is an enzyme which depends on the gestational age of the newborn. After the 32nd week of gestation the enzyme becomes active. Moreover pyridoxalkinase is an enzyme that can be induced by formulas containing vitamin B6. We consider the administration of vitamin B6 to the preterm infant as necessary."} {"id": "PMID:175342", "title": "[Antibodies against the Epstein-Barr virus, capsid antigen in children with malignant neoplasms (author's transl)].", "content": "Sera from children were tested for antibodies to viral capsid antigens of Epstein-Barr virus. The method applied was the indirect immunofluorescence test. 25 sera from healthy donors were titrated as controls. In 14 patients with acute lymphocytic leukemia we found low levels, a tiny little girl with chronic myelocytic leukemia (?) AND THREE CHILDREN.WITH LYMPHOPROLIFERATIVE DISORDERS SHOWed highly increased serological reactivities. Investigated children with other kinds of tumours did not serologically differ significantly from the control group. Further investigations should clarify the role of this infectious agent.", "contents": "[Antibodies against the Epstein-Barr virus, capsid antigen in children with malignant neoplasms (author's transl)]. Sera from children were tested for antibodies to viral capsid antigens of Epstein-Barr virus. The method applied was the indirect immunofluorescence test. 25 sera from healthy donors were titrated as controls. In 14 patients with acute lymphocytic leukemia we found low levels, a tiny little girl with chronic myelocytic leukemia (?) AND THREE CHILDREN.WITH LYMPHOPROLIFERATIVE DISORDERS SHOWed highly increased serological reactivities. Investigated children with other kinds of tumours did not serologically differ significantly from the control group. Further investigations should clarify the role of this infectious agent."} {"id": "PMID:175343", "title": "Control of glycolysis in skeletal muscle from fetal rhesus monkeys.", "content": "In our studies of metabolic control mechanisms in skeletal muscle from rhesus fetus we have determined the tissue levels of the metabolic intermediates and cofactors of the glycolytic pathway and have calculated the mass-action ratios for each reaction. Skeletal muscle from rhesus fetuses (Macaca mulatta), 90-155 days of gestational age, and from adult rhesus monkeys was used in these experiments. The apparent equilibrium constants for hexokinase and phosphofructokinase (PFK) in these tissues were over 1,000 times larger than the mass-action ratios at all ages studied; the corresponding values for pyruvate kinase were more than 800 times different. The data suggest that these three enzymes are rate-limiting for fetal skeletal muscle as early as 54% of gestation. The next step was to study some of the numerous factors that modify these non-equilibrium reactions. Increasing the ATP concentration had a marked effect on the PFK activity of both fetal and adult muscle, first increasing and then inhibiting enzyme activity. At maximum PFK activity, the amount of fructose-6-PO4(F6P) phosphorylated per mg of protein was 2-3 times greater in the two fetal than in the adult series. At a concentration of 0.3 mM, citrate decreased PFK activity of the 100-day fetal muscle; a further decrease occurred at 1.2 mM citrate. At a citrate level of 0.3 mM. the addition of inorganic phosphate (Pi) or cyclic AMP returned PFK activity to the uninhibited levels (pH 7.0). Relief of ATP inhibition of F6P phosphorylation with Pi and cyclic AMP was also observed at pH 7.0 in extracts of 100-day fetal skeletal muscle.", "contents": "Control of glycolysis in skeletal muscle from fetal rhesus monkeys. In our studies of metabolic control mechanisms in skeletal muscle from rhesus fetus we have determined the tissue levels of the metabolic intermediates and cofactors of the glycolytic pathway and have calculated the mass-action ratios for each reaction. Skeletal muscle from rhesus fetuses (Macaca mulatta), 90-155 days of gestational age, and from adult rhesus monkeys was used in these experiments. The apparent equilibrium constants for hexokinase and phosphofructokinase (PFK) in these tissues were over 1,000 times larger than the mass-action ratios at all ages studied; the corresponding values for pyruvate kinase were more than 800 times different. The data suggest that these three enzymes are rate-limiting for fetal skeletal muscle as early as 54% of gestation. The next step was to study some of the numerous factors that modify these non-equilibrium reactions. Increasing the ATP concentration had a marked effect on the PFK activity of both fetal and adult muscle, first increasing and then inhibiting enzyme activity. At maximum PFK activity, the amount of fructose-6-PO4(F6P) phosphorylated per mg of protein was 2-3 times greater in the two fetal than in the adult series. At a concentration of 0.3 mM, citrate decreased PFK activity of the 100-day fetal muscle; a further decrease occurred at 1.2 mM citrate. At a citrate level of 0.3 mM. the addition of inorganic phosphate (Pi) or cyclic AMP returned PFK activity to the uninhibited levels (pH 7.0). Relief of ATP inhibition of F6P phosphorylation with Pi and cyclic AMP was also observed at pH 7.0 in extracts of 100-day fetal skeletal muscle."} {"id": "PMID:175344", "title": "Neonatal diagnosis of familial type II hyperlipoproteinemia.", "content": "Cord serum prebeta-beta-lipoprotein concentration was measured in a radial immunodiffusion assay in 303 randomly selected, full-term infants whose parental phenotypes were unknown. Six infants had elevated concentrations, that is above a cut-off limit of 197 mg/100 ml (97.5th percentile). Three of these infants suffered from classic type II hyperlipoproteinemia, and this diagnosis was confirmed by family studies at follow-up. The three other infants and their parents were shown to be normolipemic at follow-up. The elevated cord serum prebeta-beta-lipoprotein in these three infants could be explained by highly elevated cord serum triglyceride and/or cholesterol. The 297 infants with normal cord serum prebeta-beta-lipoprotein and their parents were all shown to be normalipemic at follow-up. It is concluded that the measurement of prebeta-beta-lipoportein in cord serum allows the identification of children with familial type II hyperlipoproteinemia, if infants with transient neonatal hypertriglyceridemia and hypercholesterolemia are excluded.", "contents": "Neonatal diagnosis of familial type II hyperlipoproteinemia. Cord serum prebeta-beta-lipoprotein concentration was measured in a radial immunodiffusion assay in 303 randomly selected, full-term infants whose parental phenotypes were unknown. Six infants had elevated concentrations, that is above a cut-off limit of 197 mg/100 ml (97.5th percentile). Three of these infants suffered from classic type II hyperlipoproteinemia, and this diagnosis was confirmed by family studies at follow-up. The three other infants and their parents were shown to be normolipemic at follow-up. The elevated cord serum prebeta-beta-lipoprotein in these three infants could be explained by highly elevated cord serum triglyceride and/or cholesterol. The 297 infants with normal cord serum prebeta-beta-lipoprotein and their parents were all shown to be normalipemic at follow-up. It is concluded that the measurement of prebeta-beta-lipoportein in cord serum allows the identification of children with familial type II hyperlipoproteinemia, if infants with transient neonatal hypertriglyceridemia and hypercholesterolemia are excluded."} {"id": "PMID:175345", "title": "Serum 25-hydroxyvitamin D in infantile rickets.", "content": "In small children with nutritional vitamin D deficiency, the serum concentration of 25-hydroxyvitamin D (25-OH-D), the major circulating metabolite of vitamin D, was correlated with the stage of clinical disease. It was low (16 to 20 ng/ml) but within the normal range in the earliest (hypocalcemic) stage of the deficiency syndrome and decreased (less than 15 ng/ml) in the more advanced stages. In patients with familial hypophosphatemia (X-linked dominant), mean serum 25-OH-D concentration was the same as in age-matched normal controls. Evidence is presented that endogenous parathyroid hormone may have a role in the depletion of serum 25-OH0D in deficiency states.", "contents": "Serum 25-hydroxyvitamin D in infantile rickets. In small children with nutritional vitamin D deficiency, the serum concentration of 25-hydroxyvitamin D (25-OH-D), the major circulating metabolite of vitamin D, was correlated with the stage of clinical disease. It was low (16 to 20 ng/ml) but within the normal range in the earliest (hypocalcemic) stage of the deficiency syndrome and decreased (less than 15 ng/ml) in the more advanced stages. In patients with familial hypophosphatemia (X-linked dominant), mean serum 25-OH-D concentration was the same as in age-matched normal controls. Evidence is presented that endogenous parathyroid hormone may have a role in the depletion of serum 25-OH0D in deficiency states."} {"id": "PMID:175346", "title": "Color and form perception on the Rorschach as a function of eye color.", "content": "Recent research had demonstrated that dark-eyed individuals are more reactive than light-eyed people. The present paper investigated one area of reactivity, ease of emotional arousal. The hypothesis that dark-eyed male subjects (n equals 40) would show greater ease of arousal than light-eyed male subjects (n equals 40) was tested using color and form responses on the Rorschach as dependent measures. The predicted interaction was significant; light-eyed subjects gave relatively more form responses, but dark-eyed subjects gave relatively more color responses. Implications for future research and application were discussed.", "contents": "Color and form perception on the Rorschach as a function of eye color. Recent research had demonstrated that dark-eyed individuals are more reactive than light-eyed people. The present paper investigated one area of reactivity, ease of emotional arousal. The hypothesis that dark-eyed male subjects (n equals 40) would show greater ease of arousal than light-eyed male subjects (n equals 40) was tested using color and form responses on the Rorschach as dependent measures. The predicted interaction was significant; light-eyed subjects gave relatively more form responses, but dark-eyed subjects gave relatively more color responses. Implications for future research and application were discussed."} {"id": "PMID:175351", "title": "[Bone scintigraphy with 99mTc-pyrophosphate: pharmokinetics of the substance and clinical experiences with the scintigraphy].", "content": "Kinetics and clinical studies of bone scintiscanning with 99mTc-pyrophosphate in 92 patients with certified diagnosis allowed the following conclusions: 1. After i.v. injection 99mTc-pyrophosphate is distributed in 3 compartments, from which it is cleared with biological half-lives of 32.7 minutes, 5.1 hours and 22.54 hours respectively. The relative size of these compartments is 1 : 3 : 6. After application of the substance, an initially high renal excretion with a consecutive exponential drop can be observed. The optimal period for scintigraphic studies seems therefore to be from 3-6 hrs, as at this time there is still an adequate activity in bone structures, while the low background activity yields a good contrast on scintiscans. 2. The clinical results of bone scintigraphy with 99mTc-pyrophosphate with 88.6% correct diagnoses can be considered as \"very good\". This feature can partly be attributed to an improved correlation of radiographic and scintigraphic images by the use of a specially designed, combined radiographic-photoscanning detector system. 3. Preliminary results concerning the quantitative uptake of 99mTc-pyrophosphate in fractures of the extremities suggest, that the quantitative analyses of the registered data can provide valuable prognostic information in traumatic, inflammatory and neoplastic bone lesions.", "contents": "[Bone scintigraphy with 99mTc-pyrophosphate: pharmokinetics of the substance and clinical experiences with the scintigraphy]. Kinetics and clinical studies of bone scintiscanning with 99mTc-pyrophosphate in 92 patients with certified diagnosis allowed the following conclusions: 1. After i.v. injection 99mTc-pyrophosphate is distributed in 3 compartments, from which it is cleared with biological half-lives of 32.7 minutes, 5.1 hours and 22.54 hours respectively. The relative size of these compartments is 1 : 3 : 6. After application of the substance, an initially high renal excretion with a consecutive exponential drop can be observed. The optimal period for scintigraphic studies seems therefore to be from 3-6 hrs, as at this time there is still an adequate activity in bone structures, while the low background activity yields a good contrast on scintiscans. 2. The clinical results of bone scintigraphy with 99mTc-pyrophosphate with 88.6% correct diagnoses can be considered as \"very good\". This feature can partly be attributed to an improved correlation of radiographic and scintigraphic images by the use of a specially designed, combined radiographic-photoscanning detector system. 3. Preliminary results concerning the quantitative uptake of 99mTc-pyrophosphate in fractures of the extremities suggest, that the quantitative analyses of the registered data can provide valuable prognostic information in traumatic, inflammatory and neoplastic bone lesions."} {"id": "PMID:175352", "title": "Duplication of single stranded DNA catalyzed by calf thymus DNA polymerase alpha.", "content": "Purified calf thymus DNA polymerase alpha is inactive with native DNA as template and shows little activity with denatured DNA. DNA synthesis with denatured DNA as template is greatly stimulated by the addition of a nuclease which initially copurifies with DNA polymerase but is separated from the polymerase on DEAE-cellulose chromatography. A limit digest of nuclease treated native DNA which is then denatured is replicated 80-95%; extensive replication is also obtained with native DNA partially degraded by pancreatic DNase and then denatured. The product of the reaction with calf thymus nuclease-treated DNA as template is double-stranded DNA with a hairpin (looped back) structure.", "contents": "Duplication of single stranded DNA catalyzed by calf thymus DNA polymerase alpha. Purified calf thymus DNA polymerase alpha is inactive with native DNA as template and shows little activity with denatured DNA. DNA synthesis with denatured DNA as template is greatly stimulated by the addition of a nuclease which initially copurifies with DNA polymerase but is separated from the polymerase on DEAE-cellulose chromatography. A limit digest of nuclease treated native DNA which is then denatured is replicated 80-95%; extensive replication is also obtained with native DNA partially degraded by pancreatic DNase and then denatured. The product of the reaction with calf thymus nuclease-treated DNA as template is double-stranded DNA with a hairpin (looped back) structure."} {"id": "PMID:175353", "title": "Specific spin-labeling of transfer ribonucleic acid molecules.", "content": "The spin labels anhydride (ASL), bromoacetamide (BSL) and carbodiimide (CSL) were used to label selectively tRNAGlu, tRNA fMet and tRNAPhe from E. coli. The preparation and characterization of the sites of labeling of eight new spin-labeled tRNAs are described. The sites of labeling are: s2U using ASL, BSL and CLS and tRNAGlu; s4U using ASL and BSL on tRNAfMet and tRNAPhe; U-37 with CSL on tRNfMet; U-33 with CSL on tRNAPhe. The rare base X at position 47 of tRNAPhe has been acylated with a spin-labeled N-hydroxysuccinimide (HSL). The 3'end of unfractionated tRNA molecules has been chemically modified to a morpholino spin-labeled analogue (MSL). Their respective e.s.r. spectra are reported and discussed.", "contents": "Specific spin-labeling of transfer ribonucleic acid molecules. The spin labels anhydride (ASL), bromoacetamide (BSL) and carbodiimide (CSL) were used to label selectively tRNAGlu, tRNA fMet and tRNAPhe from E. coli. The preparation and characterization of the sites of labeling of eight new spin-labeled tRNAs are described. The sites of labeling are: s2U using ASL, BSL and CLS and tRNAGlu; s4U using ASL and BSL on tRNAfMet and tRNAPhe; U-37 with CSL on tRNfMet; U-33 with CSL on tRNAPhe. The rare base X at position 47 of tRNAPhe has been acylated with a spin-labeled N-hydroxysuccinimide (HSL). The 3'end of unfractionated tRNA molecules has been chemically modified to a morpholino spin-labeled analogue (MSL). Their respective e.s.r. spectra are reported and discussed."} {"id": "PMID:175354", "title": "A spin label study of the thermal unfolding of secondary and tertiary structure in E. colic transfer RNAs.", "content": "The molecular mechanism of thermal unfolding of E. coli tRNAGlu, tRNAfMet and tRNAPhe (in 0.02M Tris-HC1, pH 7.5. 10 MM Mg C12) has been examined by the spin-labeling technique. The rate of tumbling of the spin label has been measured as a function of temperature for ten different selectively spin-labeled tRNAs. Only spin labels at position s4U-8 were able to probe the tertiary structure. Evidences are presented which support the hypothesis that the thermal denaturation of the three species of tRNAs studied is sequential. The unfolding process occurs in three discrete stages. The first step (30 degrees-32 degrees) could either be assigned to a localized reorganization of the cold-denatured structure or to a \"transient\" melting, followed by the simultaneous disruption of the tertiary structure and part of the hU helix. This transition is observed even in the absence of magnesium. The second step (50 degrees-54 degrees) involves the melting of the anticodon and miniloop regions. The last step occurs above 65 degrees where the t psi c and amino acid acceptor stems, forming one continuous double helix, melt. A simple dynamic model is considered for tRNA function in protein biosynthesis.", "contents": "A spin label study of the thermal unfolding of secondary and tertiary structure in E. colic transfer RNAs. The molecular mechanism of thermal unfolding of E. coli tRNAGlu, tRNAfMet and tRNAPhe (in 0.02M Tris-HC1, pH 7.5. 10 MM Mg C12) has been examined by the spin-labeling technique. The rate of tumbling of the spin label has been measured as a function of temperature for ten different selectively spin-labeled tRNAs. Only spin labels at position s4U-8 were able to probe the tertiary structure. Evidences are presented which support the hypothesis that the thermal denaturation of the three species of tRNAs studied is sequential. The unfolding process occurs in three discrete stages. The first step (30 degrees-32 degrees) could either be assigned to a localized reorganization of the cold-denatured structure or to a \"transient\" melting, followed by the simultaneous disruption of the tertiary structure and part of the hU helix. This transition is observed even in the absence of magnesium. The second step (50 degrees-54 degrees) involves the melting of the anticodon and miniloop regions. The last step occurs above 65 degrees where the t psi c and amino acid acceptor stems, forming one continuous double helix, melt. A simple dynamic model is considered for tRNA function in protein biosynthesis."} {"id": "PMID:175364", "title": "Specific oligoribonucleotide synthesis using primer-independent polynucleotide phosphorylase.", "content": "Oligoribonucleotides of a predetermined base sequence beginning with adenylyl-3', 5'-adenosine at the 5' end have been synthesized in yields varying between 13% and 42%. The synthesis was carried out using primer-independent polynucleotide phosphorylase from E. coli in the presence of high concentrations of primer and of sodium chloride.", "contents": "Specific oligoribonucleotide synthesis using primer-independent polynucleotide phosphorylase. Oligoribonucleotides of a predetermined base sequence beginning with adenylyl-3', 5'-adenosine at the 5' end have been synthesized in yields varying between 13% and 42%. The synthesis was carried out using primer-independent polynucleotide phosphorylase from E. coli in the presence of high concentrations of primer and of sodium chloride."} {"id": "PMID:175365", "title": "The autonomic nervous system in alcoholic and diabetic neuropathy.", "content": "Tests of autonomic function were performed on 10 controls, 16 subjects with diabetic neuropathy and 12 subjects with alcoholic neuropathy. Abnormal sweating occurred in 10/10 alcoholics (100%) and 10/10 diabetics (100%) who were examined. An abnormal Valsalva ratio was present in 7/11 (64%) of diabetics and only 2/9 (22%) of alcoholics. Denervation hypersensitivity to phenylephrine occurred in 2/8 (25%) of diabetics and was absent in alcoholics. A quantitative assessment of baroreceptor function was made. In diabetics there was a reduced resting heart period, heart period range and mean gain, whilst these parameters were essentially normal in alcoholics.", "contents": "The autonomic nervous system in alcoholic and diabetic neuropathy. Tests of autonomic function were performed on 10 controls, 16 subjects with diabetic neuropathy and 12 subjects with alcoholic neuropathy. Abnormal sweating occurred in 10/10 alcoholics (100%) and 10/10 diabetics (100%) who were examined. An abnormal Valsalva ratio was present in 7/11 (64%) of diabetics and only 2/9 (22%) of alcoholics. Denervation hypersensitivity to phenylephrine occurred in 2/8 (25%) of diabetics and was absent in alcoholics. A quantitative assessment of baroreceptor function was made. In diabetics there was a reduced resting heart period, heart period range and mean gain, whilst these parameters were essentially normal in alcoholics."} {"id": "PMID:175367", "title": "Autonomic disturbances produced by lung cancer: a report of two unusual cases.", "content": "Two cases of malignant infiltration of nerve are presented in whom a major feature was excessive spontaneous sweat secretion. The possible mechanisms for the production of this unusual symptom are discussed.", "contents": "Autonomic disturbances produced by lung cancer: a report of two unusual cases. Two cases of malignant infiltration of nerve are presented in whom a major feature was excessive spontaneous sweat secretion. The possible mechanisms for the production of this unusual symptom are discussed."} {"id": "PMID:175368", "title": "Purification and buoyant density of infectious bovine rhinotracheitis virus.", "content": "A purification scheme for infectious bovine rhinotracheitis virus utilizing rate-zonal centrifugation in a 10-40% potassium tartrate gradient was described. The density of IBRV in the potassium tartrate gradient was found to be 1.22 g/cm3. Electron microscopic examination of purified virus preparations revealed homogeneous populations of enveloped virions with minute projections on the envelope surface.", "contents": "Purification and buoyant density of infectious bovine rhinotracheitis virus. A purification scheme for infectious bovine rhinotracheitis virus utilizing rate-zonal centrifugation in a 10-40% potassium tartrate gradient was described. The density of IBRV in the potassium tartrate gradient was found to be 1.22 g/cm3. Electron microscopic examination of purified virus preparations revealed homogeneous populations of enveloped virions with minute projections on the envelope surface."} {"id": "PMID:175369", "title": "The involvement of cyclic-3',5'-AMP in the release of hormones from the anterior pituitary in vitro.", "content": "DBcAMP significantly increased the release of GH but not of LH, FSH, TSH, or PRL, except in the presence of hypothalamic extract when it augmented the release of LH, FSH, and GH, reversed the inhibition of PRL, but did not further influence TSH release. Theophylline increased release of GH and PRL while inducing increased tissue content of cAMP without consistently increasing the release of TSH, LH, or FSH. Hypothalamic extractor K+-stimulated hormone rel-ase was consistently and significantly potentiated by theophylline. Neither hypothalamic extract, increased [K+], or synthetic TRH and LRH were able to raise tissue content of cAMP while producing their expected effects on hormone release. Cholera enterotoxin produced a highly significant increase in tissue content of the cyclic nucleotide but increased the release of GH only, and not that of LH, FSH, TSH, or PRL. DBcAMP was able to lower the threshold concentration of K+ required to stimulate release of GH, LH, and FSH and also to augment K+-stimulated release to the higher levels induced by the hypothalamic releasing hormones. It did not augment K+-induced release of TSH.", "contents": "The involvement of cyclic-3',5'-AMP in the release of hormones from the anterior pituitary in vitro. DBcAMP significantly increased the release of GH but not of LH, FSH, TSH, or PRL, except in the presence of hypothalamic extract when it augmented the release of LH, FSH, and GH, reversed the inhibition of PRL, but did not further influence TSH release. Theophylline increased release of GH and PRL while inducing increased tissue content of cAMP without consistently increasing the release of TSH, LH, or FSH. Hypothalamic extractor K+-stimulated hormone rel-ase was consistently and significantly potentiated by theophylline. Neither hypothalamic extract, increased [K+], or synthetic TRH and LRH were able to raise tissue content of cAMP while producing their expected effects on hormone release. Cholera enterotoxin produced a highly significant increase in tissue content of the cyclic nucleotide but increased the release of GH only, and not that of LH, FSH, TSH, or PRL. DBcAMP was able to lower the threshold concentration of K+ required to stimulate release of GH, LH, and FSH and also to augment K+-stimulated release to the higher levels induced by the hypothalamic releasing hormones. It did not augment K+-induced release of TSH."} {"id": "PMID:175370", "title": "Effects of LH-RH on isolated pituitary gonadotropic cells.", "content": "Rat anterior pituitary glands were dissociated with Pronase and the cells were separated by velocity sedimentation at unit gravity. After 30 min of incubation of the enriched gonadotropic cells with LH-RH, there was a significant increase in LH and FSH in the incubation medium. LH-RH (100 ng/ml) and 10(-3) M cAMP both caused significant increases in LH in the incubation medium after 24 hr of incubation.", "contents": "Effects of LH-RH on isolated pituitary gonadotropic cells. Rat anterior pituitary glands were dissociated with Pronase and the cells were separated by velocity sedimentation at unit gravity. After 30 min of incubation of the enriched gonadotropic cells with LH-RH, there was a significant increase in LH and FSH in the incubation medium. LH-RH (100 ng/ml) and 10(-3) M cAMP both caused significant increases in LH in the incubation medium after 24 hr of incubation."} {"id": "PMID:175371", "title": "Effects of hypothalamic-releasing hormones on LH, FSH, and prolactin in pituitary monolayer cultures.", "content": "Four-day-old pituitary monolayer cultures were incubated with various hypothalamic releasing hormones. Rat hypothalamic extract stimulated the release of LH, FSH, and PRL by these cultures in a dose-related fashion. Synthetic LH-RH stimulated the release of LH and FSH but not of PRL. Synthetic TRH increased the release of PRL but had no effect on LH or FSH. At 10(-8) M, somatostatin did not affect any of the three adenohypophyseal hormones. Incubation with DBcAMP or theophylline also stimulated PRL release without any detectable effect on LH and FSH release. These data suggest the involvement of cyclic AMP--adenylate cyclase system in the mechanism of PRL release, but their involvement in gonadotropin release requires further studies.", "contents": "Effects of hypothalamic-releasing hormones on LH, FSH, and prolactin in pituitary monolayer cultures. Four-day-old pituitary monolayer cultures were incubated with various hypothalamic releasing hormones. Rat hypothalamic extract stimulated the release of LH, FSH, and PRL by these cultures in a dose-related fashion. Synthetic LH-RH stimulated the release of LH and FSH but not of PRL. Synthetic TRH increased the release of PRL but had no effect on LH or FSH. At 10(-8) M, somatostatin did not affect any of the three adenohypophyseal hormones. Incubation with DBcAMP or theophylline also stimulated PRL release without any detectable effect on LH and FSH release. These data suggest the involvement of cyclic AMP--adenylate cyclase system in the mechanism of PRL release, but their involvement in gonadotropin release requires further studies."} {"id": "PMID:175372", "title": "Influence of dietary Ca, Mg, and P on cyclic-AMP excretion and kidney calcification in the rat.", "content": "A series of five experiments was conducted with young male albino rats to investigate effects of various levels of dietary Ca, P and Mg on urinary cAMP excretion and kidney calcification. Urinary cAMP excretion was shown to be directly correlated with injected parathyroid (PT) hormone dose level and to be inversely associated with dietary Ca intake. Thus, cAMP excretion may be presumed to reflect PT activity in the young rat. Magnesium deficiency tended to reduce cAMP excretion, while P excess did not affect it. Each treatment induced kidney calcification. Calcium deficiency increased cAMP excretion irrespective of Mg status, although nephrocalcinosis appeared only in the Mg-deficient animals. These data support the view that nephrocalcinosis of dietary origin in the rat is not mediated by increased PT activity.", "contents": "Influence of dietary Ca, Mg, and P on cyclic-AMP excretion and kidney calcification in the rat. A series of five experiments was conducted with young male albino rats to investigate effects of various levels of dietary Ca, P and Mg on urinary cAMP excretion and kidney calcification. Urinary cAMP excretion was shown to be directly correlated with injected parathyroid (PT) hormone dose level and to be inversely associated with dietary Ca intake. Thus, cAMP excretion may be presumed to reflect PT activity in the young rat. Magnesium deficiency tended to reduce cAMP excretion, while P excess did not affect it. Each treatment induced kidney calcification. Calcium deficiency increased cAMP excretion irrespective of Mg status, although nephrocalcinosis appeared only in the Mg-deficient animals. These data support the view that nephrocalcinosis of dietary origin in the rat is not mediated by increased PT activity."} {"id": "PMID:175373", "title": "Macrophage migration inhibition and lymphocyte stimulation with mammary tumor virus associated antigens in Balb/c mice.", "content": "Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonresponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen.", "contents": "Macrophage migration inhibition and lymphocyte stimulation with mammary tumor virus associated antigens in Balb/c mice. Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonresponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen."} {"id": "PMID:175374", "title": "Prolyl hydroxylase activity in normal and diseased human liver.", "content": "Prolyl hydroxylase activity was determined in liver biopsy samples obtained from 10 patients. The liver prolyl hydroxylase values in patients with active hepatitis distribute into two numerical populations based on the extent of elevation over control. The first of these groups includes those with enzyme levels elevated approximately 2.5-fold over normal. Included in this group are patients with active (but nonagrressive) hepatitis and patients where advanced portal fibrosis is already established. The second group where prolyl hydroxylase is elevated approximately nine-fold is comprised of two patients with advanced clinical symptoms of active alcoholic hepatitis with evidence of aggressive cirrhosis but with only early minimal evidence of existing fibrosis.", "contents": "Prolyl hydroxylase activity in normal and diseased human liver. Prolyl hydroxylase activity was determined in liver biopsy samples obtained from 10 patients. The liver prolyl hydroxylase values in patients with active hepatitis distribute into two numerical populations based on the extent of elevation over control. The first of these groups includes those with enzyme levels elevated approximately 2.5-fold over normal. Included in this group are patients with active (but nonagrressive) hepatitis and patients where advanced portal fibrosis is already established. The second group where prolyl hydroxylase is elevated approximately nine-fold is comprised of two patients with advanced clinical symptoms of active alcoholic hepatitis with evidence of aggressive cirrhosis but with only early minimal evidence of existing fibrosis."} {"id": "PMID:175375", "title": "Rabbits as a source of antisera against SV40 virus-induced cell surface antigens.", "content": "Rabbits immunized with SV40 virus-transformed rabbit cells yielded antisera highly reactive in a mixed-hemadsorption assay against SV40-transformed hamster, mouse, and rabbit cells. Such antisera may prove of value in studies requiring large amounts of antibody angainst SV40-induced cell surface antigens.", "contents": "Rabbits as a source of antisera against SV40 virus-induced cell surface antigens. Rabbits immunized with SV40 virus-transformed rabbit cells yielded antisera highly reactive in a mixed-hemadsorption assay against SV40-transformed hamster, mouse, and rabbit cells. Such antisera may prove of value in studies requiring large amounts of antibody angainst SV40-induced cell surface antigens."} {"id": "PMID:175376", "title": "Different lipolytic effects of theophylline and dibutyryl cyclic AMP in vivo and in vitro.", "content": "Both dcAMP and theophylline are known to promote lipolysis in vitro by increasing intracellular cAMP. Although theophylline stimulates FFA mobilization in vivo as well, a report of low circulating FFA levels in the rat given dcAMP suggested that dcAMP may inhibit lipolysis in the intact animal. To explore this possibility, a comparison of the in vitro and in vivo lipolytic effects of theophylline and dcAMP was made in the young dog. Circulating glycerol and FFA levels rose following the administration of theophylline. While glycerol and FFA fell slightly in puppies given dcAMP, only the FFA change was significant. Epinephrine infusions given alone produced sustained elevations of glycerol and FFA. When theophylline was given in conjunction with ongoing epinephrine infusions, plasma glycerol and FFA levels remained high. On the other hand, epinephrine-stimulated lipolysis was markedly inhibited by dcAMP, as shown by pronounced falls of glycerol and FFA from the elevated levels found with epinephrine alone. In vitro studies involving fragments of puppy adipose tissue reveal that epinephrine, theophylline, and dcAMP promoted glycerol release. In contrast to the in vivo observations, lipolysis was also stimulated by combinations of both epinephrine and theophylline as well as by epinephrine and dcAMP. Thus, theophylline stimulates lipolysis in vitro and in vivo in the puppy. In contrast, dcAMP stimulates lipolysis in vitro but inhibits this action in the intact animal. This important difference in the two pharmacologic agents suggests the need for caution when using them in in vivo studies involving the action of cAMP.", "contents": "Different lipolytic effects of theophylline and dibutyryl cyclic AMP in vivo and in vitro. Both dcAMP and theophylline are known to promote lipolysis in vitro by increasing intracellular cAMP. Although theophylline stimulates FFA mobilization in vivo as well, a report of low circulating FFA levels in the rat given dcAMP suggested that dcAMP may inhibit lipolysis in the intact animal. To explore this possibility, a comparison of the in vitro and in vivo lipolytic effects of theophylline and dcAMP was made in the young dog. Circulating glycerol and FFA levels rose following the administration of theophylline. While glycerol and FFA fell slightly in puppies given dcAMP, only the FFA change was significant. Epinephrine infusions given alone produced sustained elevations of glycerol and FFA. When theophylline was given in conjunction with ongoing epinephrine infusions, plasma glycerol and FFA levels remained high. On the other hand, epinephrine-stimulated lipolysis was markedly inhibited by dcAMP, as shown by pronounced falls of glycerol and FFA from the elevated levels found with epinephrine alone. In vitro studies involving fragments of puppy adipose tissue reveal that epinephrine, theophylline, and dcAMP promoted glycerol release. In contrast to the in vivo observations, lipolysis was also stimulated by combinations of both epinephrine and theophylline as well as by epinephrine and dcAMP. Thus, theophylline stimulates lipolysis in vitro and in vivo in the puppy. In contrast, dcAMP stimulates lipolysis in vitro but inhibits this action in the intact animal. This important difference in the two pharmacologic agents suggests the need for caution when using them in in vivo studies involving the action of cAMP."} {"id": "PMID:175377", "title": "Progesterone binding in rabbit oviduct and uterus.", "content": "Progesterone binding of high affinity with a dissociation constant of 10(-9) M was identified in cytosol of rabbit oviduct and uterus. Macromolecules with sedimentation coefficients of 7-8 S and 4-5 S were present. Progesterone receptor concentration was two to fivefold lower in the oviduct when compared with the uterus. The receptor concentration declined steadily from 3 hr until 144 hr after mating in the uterus; however, the decline in oviductal receptor was not significant until the sixth day of pregnancy. Progesterone receptor concentration in rabbit oviduct and uterus in estrus and early pregnancy was greater than estradiol receptor levels.", "contents": "Progesterone binding in rabbit oviduct and uterus. Progesterone binding of high affinity with a dissociation constant of 10(-9) M was identified in cytosol of rabbit oviduct and uterus. Macromolecules with sedimentation coefficients of 7-8 S and 4-5 S were present. Progesterone receptor concentration was two to fivefold lower in the oviduct when compared with the uterus. The receptor concentration declined steadily from 3 hr until 144 hr after mating in the uterus; however, the decline in oviductal receptor was not significant until the sixth day of pregnancy. Progesterone receptor concentration in rabbit oviduct and uterus in estrus and early pregnancy was greater than estradiol receptor levels."} {"id": "PMID:175378", "title": "Deoxycytidine kinase from rabbit kidney cells infected with herpes simplex virus type 1 or 2.", "content": "When rabbit kidney cells were infected with herpes simplex virus type 1 (strain Seibert) or herpes simplex virus type 2 (strain 316D), deoxycytidine kinase (CdR kinase) activity, assayed at 38 degrees, increased 5- to 15-fold relative to controls. The CdR kinase activity induced by type 2 virus was more thermolabile than the enzyme activity induced by type 1 virus. When CdR kinase activity was assayed at various temperatures between 0.5 and 38 degrees, maximum activity for type 1 enzyme was obtained at 16 degrees while maximum activities for host and type 2 enzymes were obtained at 38 degrees. Both type 1 and type 2 induced CdR kinase activities eluted at the same positions as deoxythymidine kinase activities on a Sephadex G-100 column. The estimated mol wt for HSV-1 (Seibert) and HSV-2 (316D) induced CdR kinases are 67,000 and 60,000, respectively.", "contents": "Deoxycytidine kinase from rabbit kidney cells infected with herpes simplex virus type 1 or 2. When rabbit kidney cells were infected with herpes simplex virus type 1 (strain Seibert) or herpes simplex virus type 2 (strain 316D), deoxycytidine kinase (CdR kinase) activity, assayed at 38 degrees, increased 5- to 15-fold relative to controls. The CdR kinase activity induced by type 2 virus was more thermolabile than the enzyme activity induced by type 1 virus. When CdR kinase activity was assayed at various temperatures between 0.5 and 38 degrees, maximum activity for type 1 enzyme was obtained at 16 degrees while maximum activities for host and type 2 enzymes were obtained at 38 degrees. Both type 1 and type 2 induced CdR kinase activities eluted at the same positions as deoxythymidine kinase activities on a Sephadex G-100 column. The estimated mol wt for HSV-1 (Seibert) and HSV-2 (316D) induced CdR kinases are 67,000 and 60,000, respectively."} {"id": "PMID:175379", "title": "Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes.", "content": "The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic.", "contents": "Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes. The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic."} {"id": "PMID:175380", "title": "Induction of SMON-type virus form avian infectious laryngotracheitis virus.", "content": "SMON-type virus which shows different host range was induced from ILT virus under unsuitable culture conditions for the growth of the parental ILT virus, such as cultivation in CAM of 12-day-old eggs or cultivation in CHK cells at 32 degrees. Furthermore, it was induced from ILT virus by mutagenesis by either BrdU or NG in CHK cell cultures.", "contents": "Induction of SMON-type virus form avian infectious laryngotracheitis virus. SMON-type virus which shows different host range was induced from ILT virus under unsuitable culture conditions for the growth of the parental ILT virus, such as cultivation in CAM of 12-day-old eggs or cultivation in CHK cells at 32 degrees. Furthermore, it was induced from ILT virus by mutagenesis by either BrdU or NG in CHK cell cultures."} {"id": "PMID:175381", "title": "Characterization of a triglyceride hydrolase secreted by canine liver maintained in vitro.", "content": "These studies demonstrate that canine liver synthesizes a TGH activated by C-I but not by C-II. This TGH has properties similar to lipoprotein lipase C-I isolated from postheparin plasma of human subjects, but differs from a previously reported liver triglyceride-lipase or protamine insensitive-lipase in its sensitivity to NaCl and protamine sulfate, as well as in its requirement for a serum cofactor, C-I. These data suggest the possiblity that, in dogs, liver is a source of plasma LPLC-I.", "contents": "Characterization of a triglyceride hydrolase secreted by canine liver maintained in vitro. These studies demonstrate that canine liver synthesizes a TGH activated by C-I but not by C-II. This TGH has properties similar to lipoprotein lipase C-I isolated from postheparin plasma of human subjects, but differs from a previously reported liver triglyceride-lipase or protamine insensitive-lipase in its sensitivity to NaCl and protamine sulfate, as well as in its requirement for a serum cofactor, C-I. These data suggest the possiblity that, in dogs, liver is a source of plasma LPLC-I."} {"id": "PMID:175382", "title": "Growth characteristics of bovine herpesvirus 1 (infectious bovine rhinotracheitis) in human diploid cell strain WI-38.", "content": "IBR virus was found to replicate in WI-38 cells. At a high input multiplicity the virus yield was comparable to that obtained in bovine cells, but comparable degree of CPE took longer to achieve. At a low input multiplicity of IBR virus, such as may be encountered in virus contaminated bovine serum, virus yield was only about 1% of that in bovine cells, with 50% of the cells showing CPE, followed by cell regrowth. Infectious virus was not recoverable from the regrown cells by 5 weeks after initial infection, and these regrown cells were susceptible to reinfection with IBR virus. Aging of WI-38 cells in cultures for as little as 1 week reduced IBR virus yield to 90% less than the yield from the same lot of cells inoculated 7 days earlier.", "contents": "Growth characteristics of bovine herpesvirus 1 (infectious bovine rhinotracheitis) in human diploid cell strain WI-38. IBR virus was found to replicate in WI-38 cells. At a high input multiplicity the virus yield was comparable to that obtained in bovine cells, but comparable degree of CPE took longer to achieve. At a low input multiplicity of IBR virus, such as may be encountered in virus contaminated bovine serum, virus yield was only about 1% of that in bovine cells, with 50% of the cells showing CPE, followed by cell regrowth. Infectious virus was not recoverable from the regrown cells by 5 weeks after initial infection, and these regrown cells were susceptible to reinfection with IBR virus. Aging of WI-38 cells in cultures for as little as 1 week reduced IBR virus yield to 90% less than the yield from the same lot of cells inoculated 7 days earlier."} {"id": "PMID:175387", "title": "A model of the mechanisms of memory.", "content": "The neuronal information is formed by 2 waves: electronic and ionic, which enter the neuron at the level of the excited synapses. The neurofilaments lead to the transmission of the electronic wave, while the microtubules direct the ionic wave. Arriving at the level of the nuclear membrane, the electronic wave of excitation enters the system DNA-histones, which works as a computer. The electronic wave is retransmited to a bundle of neurofilaments, then it is carried to a certain collateral of the axon. In its movement, the electronic wave guides the ionic wave toward certain synapses, so that the specific connections between the input and the output signals are assured.", "contents": "A model of the mechanisms of memory. The neuronal information is formed by 2 waves: electronic and ionic, which enter the neuron at the level of the excited synapses. The neurofilaments lead to the transmission of the electronic wave, while the microtubules direct the ionic wave. Arriving at the level of the nuclear membrane, the electronic wave of excitation enters the system DNA-histones, which works as a computer. The electronic wave is retransmited to a bundle of neurofilaments, then it is carried to a certain collateral of the axon. In its movement, the electronic wave guides the ionic wave toward certain synapses, so that the specific connections between the input and the output signals are assured."} {"id": "PMID:175388", "title": "Lateral-volar finger flap for the treatment of burn syndactyly.", "content": "To completely open the web space in burn syndactyly and provide tissue that is pliable and elastic, we describe a flap from the lateral and volar surfaces of an adjacent finger which will completely cover the opened defect. The results of this procedure in 24 web spaces are reported.", "contents": "Lateral-volar finger flap for the treatment of burn syndactyly. To completely open the web space in burn syndactyly and provide tissue that is pliable and elastic, we describe a flap from the lateral and volar surfaces of an adjacent finger which will completely cover the opened defect. The results of this procedure in 24 web spaces are reported."} {"id": "PMID:175389", "title": "Disruption of healed scars in scurvy -- the result of a disequilibrium in collagen metabolism.", "content": "Old scars break open in scorbutic patients because (1) the rate of collagen degradation is greater in an old scar than it is in normal skin, and (2) the rate of collagen synthesis is diminished throughout the body in ascorbate deficiency.", "contents": "Disruption of healed scars in scurvy -- the result of a disequilibrium in collagen metabolism. Old scars break open in scorbutic patients because (1) the rate of collagen degradation is greater in an old scar than it is in normal skin, and (2) the rate of collagen synthesis is diminished throughout the body in ascorbate deficiency."} {"id": "PMID:175390", "title": "[Action of alpha-methyl-dopa on waking-sleep cycles in two inbred strains of mice, C57BR and C57BL/6 (author's transl)].", "content": "The effects of alpha-methyl-Dopa at several dose levels on waking-sleep cycle of 175 mice from two inbred strains (C57BR and C57BL/6) have been studied. The results showed that each dose (25, 50, 100, 200 and 400 mg/kg), of alpha-methyl-Dopa completely suppresses paradoxical sleep (PS), after a period of sedation. Duration of PS inhibition varied as a function of dose, time of injection, and strain of mice. Using a multiple injection schedule of one injection per day for 5 consecutive days, there was suppression of nocturnal PS followed at the 4th day by rebound during day light hours.", "contents": "[Action of alpha-methyl-dopa on waking-sleep cycles in two inbred strains of mice, C57BR and C57BL/6 (author's transl)]. The effects of alpha-methyl-Dopa at several dose levels on waking-sleep cycle of 175 mice from two inbred strains (C57BR and C57BL/6) have been studied. The results showed that each dose (25, 50, 100, 200 and 400 mg/kg), of alpha-methyl-Dopa completely suppresses paradoxical sleep (PS), after a period of sedation. Duration of PS inhibition varied as a function of dose, time of injection, and strain of mice. Using a multiple injection schedule of one injection per day for 5 consecutive days, there was suppression of nocturnal PS followed at the 4th day by rebound during day light hours."} {"id": "PMID:175391", "title": "Excitation-mediating and inhibition-mediating dopamine-receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data.", "content": "A great number of earlier reported experimental data dealing with the role of dopamine in dopamine-loaded structures within the mammalian brain have raised questions concerning the concept of dopamine as an inhibitory agent acting on one type of receptor. A critical review of the anatomical, histochemical, electrophysiological, pharmacological and functional studies reveals that the dopamine-loaded structures are marked by an internal differentiation at various levels. It is attempted to demonstrate that this is due to a heterogeneous distribution of two distinct types of dopamine-receptors, each characterized by their own properties: DAe and DAi-receptors. Furthermore, the experimental and clinical implications are discussed in view of the hypothesis that balance between both types of receptors is essential for normal psychomotor functioning.", "contents": "Excitation-mediating and inhibition-mediating dopamine-receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. A great number of earlier reported experimental data dealing with the role of dopamine in dopamine-loaded structures within the mammalian brain have raised questions concerning the concept of dopamine as an inhibitory agent acting on one type of receptor. A critical review of the anatomical, histochemical, electrophysiological, pharmacological and functional studies reveals that the dopamine-loaded structures are marked by an internal differentiation at various levels. It is attempted to demonstrate that this is due to a heterogeneous distribution of two distinct types of dopamine-receptors, each characterized by their own properties: DAe and DAi-receptors. Furthermore, the experimental and clinical implications are discussed in view of the hypothesis that balance between both types of receptors is essential for normal psychomotor functioning."} {"id": "PMID:175395", "title": "A syndrome of widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness (the Singleton-Merten syndrome).", "content": "Two patients with clinical and radiological features similar to those of Singleton and Merten's patients are described. These patients exhibit features of a unique clinical syndrome of unknown etiology: generalized muscular weakness with secondary hip and foot deformities, progressive calcification of the thoracic aorta beginning in childhood, calcific aortic stenosis leading to heart failure, dysplasia of the teeth, poor physical development, osteoporosis, expanded medullary cavities of the metacarpal and metatarsal bones, and chronic psoriaform skin lesions.", "contents": "A syndrome of widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness (the Singleton-Merten syndrome). Two patients with clinical and radiological features similar to those of Singleton and Merten's patients are described. These patients exhibit features of a unique clinical syndrome of unknown etiology: generalized muscular weakness with secondary hip and foot deformities, progressive calcification of the thoracic aorta beginning in childhood, calcific aortic stenosis leading to heart failure, dysplasia of the teeth, poor physical development, osteoporosis, expanded medullary cavities of the metacarpal and metatarsal bones, and chronic psoriaform skin lesions."} {"id": "PMID:175396", "title": "The arthropathy of hemochromatosis.", "content": "Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase.", "contents": "The arthropathy of hemochromatosis. Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase."} {"id": "PMID:175397", "title": "Diffuse cavernous hemangioma of the colon in the Klippel-Trenaunay syndrome.", "content": "Large, infiltrative cavernous hemangiomas of the distal colon were present in 3 children with the Klippel-Trenaunay syndrome, 2 of whom are the subject of this report. The lesion is manifested clinically as intermittent rectal bleeding starting in the first 5 years of life. The radiographic features include (a) varicose lesions in the wall of the rectosigmoid, ranging from a network of distended submucosal veins to nodular defects, (b) narrowing of the rectum by the surrounding extramural portion of the hemangioma, and (c) phleboliths within the lesion. Inferior mesenteric angiography and sigmoidoscopy are useful for preoperative confirmation. The occurrence of visceral hemangiomas in the Klippel-Trenaunay syndrome and its relevant diagnostic and therapeutic implications are discussed.", "contents": "Diffuse cavernous hemangioma of the colon in the Klippel-Trenaunay syndrome. Large, infiltrative cavernous hemangiomas of the distal colon were present in 3 children with the Klippel-Trenaunay syndrome, 2 of whom are the subject of this report. The lesion is manifested clinically as intermittent rectal bleeding starting in the first 5 years of life. The radiographic features include (a) varicose lesions in the wall of the rectosigmoid, ranging from a network of distended submucosal veins to nodular defects, (b) narrowing of the rectum by the surrounding extramural portion of the hemangioma, and (c) phleboliths within the lesion. Inferior mesenteric angiography and sigmoidoscopy are useful for preoperative confirmation. The occurrence of visceral hemangiomas in the Klippel-Trenaunay syndrome and its relevant diagnostic and therapeutic implications are discussed."} {"id": "PMID:175400", "title": "The effect of non-steroid anti-inflammatory drugs, dibutyryl cyclic 3',5'-adenosine monophosphate and phosphodiesterase inhibitors on platelet aggregation and the platelet release reaction in normal and essential fatty acid deficient rats.", "content": "A comparison was made of the action of three classes of substances with platelet aggregation inhibiting effect in normal and essential fatty acid deficient rats. In the latter group, the effect of indomethacin was considerably reduced, whereas the difference was smaller with aspirin. Dibutyryl cyclic AMP had the same inhibiting effect in both groups. Of the phosphodiesterase inhibitors tested, dipyridamole was inactive, whereas the inhibiting effects of caffeine and papaverine are slightly reduced in the deficient animals. The same differences between the two groups were seen in the magnitude of the release reaction after 14C-serotonin labelling. These data support the idea that the non-steroid anti-inflammatory drugs act by inhibiting the formation of an aggregation-inducing substance from arachidonic acid.", "contents": "The effect of non-steroid anti-inflammatory drugs, dibutyryl cyclic 3',5'-adenosine monophosphate and phosphodiesterase inhibitors on platelet aggregation and the platelet release reaction in normal and essential fatty acid deficient rats. A comparison was made of the action of three classes of substances with platelet aggregation inhibiting effect in normal and essential fatty acid deficient rats. In the latter group, the effect of indomethacin was considerably reduced, whereas the difference was smaller with aspirin. Dibutyryl cyclic AMP had the same inhibiting effect in both groups. Of the phosphodiesterase inhibitors tested, dipyridamole was inactive, whereas the inhibiting effects of caffeine and papaverine are slightly reduced in the deficient animals. The same differences between the two groups were seen in the magnitude of the release reaction after 14C-serotonin labelling. These data support the idea that the non-steroid anti-inflammatory drugs act by inhibiting the formation of an aggregation-inducing substance from arachidonic acid."} {"id": "PMID:175406", "title": "[Morphological and enzymatic studies of the supratumoral distended colonic loop in colorectal cancers (therapeutic aspects)].", "content": "The authors carried out experimental and clinical studies in an attempt to explain the causes leading to anastomotic dehiscences, a major complication of exeresis surgery of the left colon and of the rectum. In this view they have performed in dogs incomplete stenoses at the level of the sigmoid and also made parallel studies of the morphological and histochemical changes occuring in the supra-stenosis colon wall, with those of the supra-tumoral colon wall found in human colo-rectal carcinomas, in the \"sub-occlusion\" stage. Histological alterations are presented, characterized by marked edema in all the layers of the wall, leading to evidently hampered colon vascularization. From the enzymological viewpoint there was noted an intensive phosphatasic and ATP-ase reaction in all the layers of the colon wall. These studies led to the conclusion that it is necessary to evaluate the degree and the duration of the supra-tumoral colic distension before a decision is taken to carry out primary colectomy or rectal resection (single-step procedure), and not to avoid the practice of a seriated intervention when necessary. The reversibility of the lesions noted by the authors allows for the possibility to perform a resection after the colic wall to be anastomosed has returned to an almost normal condition, thus avoiding the dehiscence of the sutures.", "contents": "[Morphological and enzymatic studies of the supratumoral distended colonic loop in colorectal cancers (therapeutic aspects)]. The authors carried out experimental and clinical studies in an attempt to explain the causes leading to anastomotic dehiscences, a major complication of exeresis surgery of the left colon and of the rectum. In this view they have performed in dogs incomplete stenoses at the level of the sigmoid and also made parallel studies of the morphological and histochemical changes occuring in the supra-stenosis colon wall, with those of the supra-tumoral colon wall found in human colo-rectal carcinomas, in the \"sub-occlusion\" stage. Histological alterations are presented, characterized by marked edema in all the layers of the wall, leading to evidently hampered colon vascularization. From the enzymological viewpoint there was noted an intensive phosphatasic and ATP-ase reaction in all the layers of the colon wall. These studies led to the conclusion that it is necessary to evaluate the degree and the duration of the supra-tumoral colic distension before a decision is taken to carry out primary colectomy or rectal resection (single-step procedure), and not to avoid the practice of a seriated intervention when necessary. The reversibility of the lesions noted by the authors allows for the possibility to perform a resection after the colic wall to be anastomosed has returned to an almost normal condition, thus avoiding the dehiscence of the sutures."} {"id": "PMID:175411", "title": "Fatty acid oxidation by ischemic myocardium.", "content": "Ischemia markedly depresses fatty acid oxidation and increases fatty acyl-CoA and fatty acylcarnitine levels in the isolated heart during palmitate oxidation. Evidence suggests that the major defect is impaired beta-oxidation due to decreased electron transport rather than to diminished fatty acyl uptake, activation, or intramitochondrial transfer. Important metabolic effects may include decreased mitochondrial adenine nucleotide translocation and altered carnitine-palmity-l-CoA transferase activity.", "contents": "Fatty acid oxidation by ischemic myocardium. Ischemia markedly depresses fatty acid oxidation and increases fatty acyl-CoA and fatty acylcarnitine levels in the isolated heart during palmitate oxidation. Evidence suggests that the major defect is impaired beta-oxidation due to decreased electron transport rather than to diminished fatty acyl uptake, activation, or intramitochondrial transfer. Important metabolic effects may include decreased mitochondrial adenine nucleotide translocation and altered carnitine-palmity-l-CoA transferase activity."} {"id": "PMID:175412", "title": "Dependence of myocardial redox systems on the concentration of exogenous substrate.", "content": "Isolated rat hearts were perfused according to Langendorff at a range of perfusion pressures and the variations of intracellular oxygenation were studied under these conditions by optical methods. The oxygen consumption was directly related to left ventricular performance in all cases examined, the relationship being independent of both the substrate used (glucose, beta-OH-butyrate) and its concentration (2.5, 5.0, 10.0 mM). The changes in the respiratory rate were accompanied by modifications of the redox state of mitochondrial enzyme systems (reduced nicotinamide adenine dinucleotide (NADH), cytochromes) in presence of low concentration (2.5 mM) of substrate. At higher substrate concentrations (5.0, 10.0 mM), however, no change in the redox state of cytochromes and only inconsistent fluctuations of that of NADH were observed. These results suggest that the generally accepted relationship between the rate of electron transport and the degree of reduction of respiratory coenzymes exists only under special conditions (low substrate concentration). Other factors, such as the size of the pool of hydrogen available, should be considered. Furthermore, this work specifies the optimal experimental conditions for the study of mitochondrial respiratory transitions (low substrate) in the intact myocardium by means of direct optical techniques.", "contents": "Dependence of myocardial redox systems on the concentration of exogenous substrate. Isolated rat hearts were perfused according to Langendorff at a range of perfusion pressures and the variations of intracellular oxygenation were studied under these conditions by optical methods. The oxygen consumption was directly related to left ventricular performance in all cases examined, the relationship being independent of both the substrate used (glucose, beta-OH-butyrate) and its concentration (2.5, 5.0, 10.0 mM). The changes in the respiratory rate were accompanied by modifications of the redox state of mitochondrial enzyme systems (reduced nicotinamide adenine dinucleotide (NADH), cytochromes) in presence of low concentration (2.5 mM) of substrate. At higher substrate concentrations (5.0, 10.0 mM), however, no change in the redox state of cytochromes and only inconsistent fluctuations of that of NADH were observed. These results suggest that the generally accepted relationship between the rate of electron transport and the degree of reduction of respiratory coenzymes exists only under special conditions (low substrate concentration). Other factors, such as the size of the pool of hydrogen available, should be considered. Furthermore, this work specifies the optimal experimental conditions for the study of mitochondrial respiratory transitions (low substrate) in the intact myocardium by means of direct optical techniques."} {"id": "PMID:175413", "title": "Opposing regulatory influences of cyclic guanosine monophosphate and cyclic adenosine monophosphate in the control of cardiac muscle contraction.", "content": "The effects of acetylcholine chloride (ACh) and isoproterenol (Iso) on myocardial levels of guanosine 3', 5'-monophosphate (cyclic GMP) and adenosine 3', 5'-monophosphate (cyclic AMP) and on force of contraction were studied in elelctrically driven isolated rabbit atria. Incubation of atria with Tyrode's solution containing ACh (5 x 10(-7) M) produced significant decreases in contractile force that were associated with significant elevations in atrial cyclic GMP levels. Atrial levels of cyclic AMP were significantly lowered at 15 sec after the addition of ACh but were only slightly lowered at earlier time intervals. The effects of acetylcholine on force of contraction and on cyclic nucleotide levels were prevented with atropine (1 x 10(-7) M). The addition of Iso (1 x 10(-7)-M) to isolated atria produced significant increases in contractile force that were associated with significant elevations in effects of Iso on force of contraction and on cyclic nucleotide levels were prevented with practolol (1 x 10(-5) M). The increases in atrial cyclic GMP and cyclic AMP levels following addition of ACh and Iso, respectively, precede the changes in contractile force. These data support our hypothesis that cyclic AMP and cyclic GMP exert oppositional effects on cardiac contrctility.", "contents": "Opposing regulatory influences of cyclic guanosine monophosphate and cyclic adenosine monophosphate in the control of cardiac muscle contraction. The effects of acetylcholine chloride (ACh) and isoproterenol (Iso) on myocardial levels of guanosine 3', 5'-monophosphate (cyclic GMP) and adenosine 3', 5'-monophosphate (cyclic AMP) and on force of contraction were studied in elelctrically driven isolated rabbit atria. Incubation of atria with Tyrode's solution containing ACh (5 x 10(-7) M) produced significant decreases in contractile force that were associated with significant elevations in atrial cyclic GMP levels. Atrial levels of cyclic AMP were significantly lowered at 15 sec after the addition of ACh but were only slightly lowered at earlier time intervals. The effects of acetylcholine on force of contraction and on cyclic nucleotide levels were prevented with atropine (1 x 10(-7) M). The addition of Iso (1 x 10(-7)-M) to isolated atria produced significant increases in contractile force that were associated with significant elevations in effects of Iso on force of contraction and on cyclic nucleotide levels were prevented with practolol (1 x 10(-5) M). The increases in atrial cyclic GMP and cyclic AMP levels following addition of ACh and Iso, respectively, precede the changes in contractile force. These data support our hypothesis that cyclic AMP and cyclic GMP exert oppositional effects on cardiac contrctility."} {"id": "PMID:175414", "title": "Alterations in myocardial and plasma cyclic adenosine monophosphate in experimental myocardial ischemia.", "content": "Alterations in myocardial and plasma cyclic adenosine monophosphate (cyclic AMP) levels were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels 2 hr later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham occlusion. Localized coronary occlusion tended to increase plasma cAMP levels in anesthetized animals and also in concious dogs. The present study suggests that adrenergically mediated changes in tissue and plasma cyclic AMP content are early manifestations of both generalized and local myocardial ischemia and tend to reflect the magnitude of the insult.", "contents": "Alterations in myocardial and plasma cyclic adenosine monophosphate in experimental myocardial ischemia. Alterations in myocardial and plasma cyclic adenosine monophosphate (cyclic AMP) levels were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels 2 hr later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham occlusion. Localized coronary occlusion tended to increase plasma cAMP levels in anesthetized animals and also in concious dogs. The present study suggests that adrenergically mediated changes in tissue and plasma cyclic AMP content are early manifestations of both generalized and local myocardial ischemia and tend to reflect the magnitude of the insult."} {"id": "PMID:175415", "title": "Regulation of myocardial energy metabolism.", "content": "Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.", "contents": "Regulation of myocardial energy metabolism. Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition."} {"id": "PMID:175416", "title": "Lysosomes of cardiac and skeletal muscle: resolution by zonal centrifugation.", "content": "The application of zonal centrifugation to the analysis of homogenates of cardiac and skeletal muscle permits selection of fractions that are enriched in markers for lysosomes, sarcolemma, sarcoplasmic reticulum, and mitochondria. The method of disruption of normal and pathological tissue alters significantly the distribution of total protein and peaks of enzymatic activity on the gradient. Total activities of cathepsin, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and para-nitrophenylphosphatase are distributed at different concentrations of sucrose on the gradient. Beta-Glucuronidase appears to \"mark\" the sarcoplasmic reticulum, as well as lysosomes, of skeletal muscle, para-Nitrophenylphosphatase, a common marker of acid phosphatase of lysosomes, is enriched in those fractions of cardiac muscle containing the highest specific activity of ouabain-inhibited Na-K-ATPase. Thus, these two enzymes appear to have a localization in at least two separate organelles. On the other hand, these results may indicate the isolation of several \"populations\" of lysosomes that are associated constantly with distribution peaks of other organelles. In any event, attempts to correlate changes in structure of organelles of normal and pathological specimens of tissue with functional impairment, e.g., Ca2+ uptake, activity of Na-K-ATPase, etc., must include consideration of dual localization of enzymatic markers or cross contamination by populations of other organelles.", "contents": "Lysosomes of cardiac and skeletal muscle: resolution by zonal centrifugation. The application of zonal centrifugation to the analysis of homogenates of cardiac and skeletal muscle permits selection of fractions that are enriched in markers for lysosomes, sarcolemma, sarcoplasmic reticulum, and mitochondria. The method of disruption of normal and pathological tissue alters significantly the distribution of total protein and peaks of enzymatic activity on the gradient. Total activities of cathepsin, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and para-nitrophenylphosphatase are distributed at different concentrations of sucrose on the gradient. Beta-Glucuronidase appears to \"mark\" the sarcoplasmic reticulum, as well as lysosomes, of skeletal muscle, para-Nitrophenylphosphatase, a common marker of acid phosphatase of lysosomes, is enriched in those fractions of cardiac muscle containing the highest specific activity of ouabain-inhibited Na-K-ATPase. Thus, these two enzymes appear to have a localization in at least two separate organelles. On the other hand, these results may indicate the isolation of several \"populations\" of lysosomes that are associated constantly with distribution peaks of other organelles. In any event, attempts to correlate changes in structure of organelles of normal and pathological specimens of tissue with functional impairment, e.g., Ca2+ uptake, activity of Na-K-ATPase, etc., must include consideration of dual localization of enzymatic markers or cross contamination by populations of other organelles."} {"id": "PMID:175418", "title": "Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study.", "content": "Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile.", "contents": "Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study. Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile."} {"id": "PMID:175419", "title": "Effect of cadmium chloride on the rat testicular soluble selenoenzyme, glutathione peroxidase.", "content": "Thirty-six hours after male rats were injected with 25 mumoles cadmium chloride/ml/kg of body weight they exhibited decreased plasma and testicular glutathione (GSH) peroxidase activity, testicular atrophy and necrosis, and increased testicular thiobarbituric acid-reactive products. Seven days after injection, only the plasma GSH peroxidase activity returned to normal. The decrease in testicular GSH peroxidase activity was not reversible by dialysis against buffer or by the addition of selenium as buffered selenomethionine. In vitro inhibition of testicular GSH peroxidase activity occurred at 0.3 mM cadmium. All in vivo effects were prevented by a prior injection of 25 mumoles sodium selenite/ml/kg of body weight. Testicular GSH peroxidase may be the direct or indirect target of cadmium-induced testicular damage, and this damage results in lipid peroxidation.", "contents": "Effect of cadmium chloride on the rat testicular soluble selenoenzyme, glutathione peroxidase. Thirty-six hours after male rats were injected with 25 mumoles cadmium chloride/ml/kg of body weight they exhibited decreased plasma and testicular glutathione (GSH) peroxidase activity, testicular atrophy and necrosis, and increased testicular thiobarbituric acid-reactive products. Seven days after injection, only the plasma GSH peroxidase activity returned to normal. The decrease in testicular GSH peroxidase activity was not reversible by dialysis against buffer or by the addition of selenium as buffered selenomethionine. In vitro inhibition of testicular GSH peroxidase activity occurred at 0.3 mM cadmium. All in vivo effects were prevented by a prior injection of 25 mumoles sodium selenite/ml/kg of body weight. Testicular GSH peroxidase may be the direct or indirect target of cadmium-induced testicular damage, and this damage results in lipid peroxidation."} {"id": "PMID:175420", "title": "Cholesterol and beta-lipoprotein on lipid inclusions and lysosomal and mitochondrial permeability of cultured heart muscle and endothelioid cells.", "content": "Cultured rat heart endothelioid cells were used to study the effect of beta-lipoprotein and cholesterol on the production and persistence of cellular lipid inclusions. Both heart endothelioid and muscle cells were used to study the effects of beta-lipoprotein with and without cholesterol or cholesterol esters on lysosomal or mitochondrial lability. Beta lipoprotein enhanced the production and maintanence of lipid inclusions. In the concentration employed (20mg%) it alone produced no effect after 72 hours on lysosomal or mitochondrial lability but with cholesterol, cholesterol stearate, cholesterol oleate or cholesterol linoleate (5mg%) there was a trend toward labilization.", "contents": "Cholesterol and beta-lipoprotein on lipid inclusions and lysosomal and mitochondrial permeability of cultured heart muscle and endothelioid cells. Cultured rat heart endothelioid cells were used to study the effect of beta-lipoprotein and cholesterol on the production and persistence of cellular lipid inclusions. Both heart endothelioid and muscle cells were used to study the effects of beta-lipoprotein with and without cholesterol or cholesterol esters on lysosomal or mitochondrial lability. Beta lipoprotein enhanced the production and maintanence of lipid inclusions. In the concentration employed (20mg%) it alone produced no effect after 72 hours on lysosomal or mitochondrial lability but with cholesterol, cholesterol stearate, cholesterol oleate or cholesterol linoleate (5mg%) there was a trend toward labilization."} {"id": "PMID:175421", "title": "[Effects of parenteral infusion of glycerol on glycerol kinase and adenosintriphosphate in rat kidneys (author's transl)].", "content": "Effects of intravenous glycerol infusions on glycerol kinase and adenosintriphosphate in rat kidneys. Intravenous infusions of glycerol with rates near and above the average maximal turnover capacity (0,74 g.kg-1.h-1) cause alterations of the kidneys such as weight increase, decrease of protein content and activity of glycerol kinase with excretion of this enzyme in the urine. At infusion rates of 0,6 g.kg-1.h-1 and more a decrease of the ATP-content of the kidneys is observed. Effects on the liver are not consistent and only demonstrable at infusion rates above the maximal turnover rate of glycerol. The results are discussed with regard to osmotic nephrosis. The appearance of glycerol kinase in the urine is discussed as an early symptom of kidney damage.", "contents": "[Effects of parenteral infusion of glycerol on glycerol kinase and adenosintriphosphate in rat kidneys (author's transl)]. Effects of intravenous glycerol infusions on glycerol kinase and adenosintriphosphate in rat kidneys. Intravenous infusions of glycerol with rates near and above the average maximal turnover capacity (0,74 g.kg-1.h-1) cause alterations of the kidneys such as weight increase, decrease of protein content and activity of glycerol kinase with excretion of this enzyme in the urine. At infusion rates of 0,6 g.kg-1.h-1 and more a decrease of the ATP-content of the kidneys is observed. Effects on the liver are not consistent and only demonstrable at infusion rates above the maximal turnover rate of glycerol. The results are discussed with regard to osmotic nephrosis. The appearance of glycerol kinase in the urine is discussed as an early symptom of kidney damage."} {"id": "PMID:175422", "title": "[The influence of propranolol, practolol and theophylline on the plasma renin activity (author's transl)].", "content": "The stimulating effect of theophylline on the plasma renin activity (PRA) under beta-receptor blockade by propranolol or practolol was investigated in 27 patients with essential hypertension of degree I-II. After propranolol and also practolol PRA decreased about thirty per cent of the basal value, increased however by the factor of 2 to 3 after application of theophylline, in spite of the blockade of the beta-receptors indicated by a slight decrease of systolic blood pressure and heart rate. The effect of propranolol and practolol on the basal PRA was not different. Our results show the possibility, to stimulate renin secretion despite blockade of beta receptors by propranolol or practolol, respectively.", "contents": "[The influence of propranolol, practolol and theophylline on the plasma renin activity (author's transl)]. The stimulating effect of theophylline on the plasma renin activity (PRA) under beta-receptor blockade by propranolol or practolol was investigated in 27 patients with essential hypertension of degree I-II. After propranolol and also practolol PRA decreased about thirty per cent of the basal value, increased however by the factor of 2 to 3 after application of theophylline, in spite of the blockade of the beta-receptors indicated by a slight decrease of systolic blood pressure and heart rate. The effect of propranolol and practolol on the basal PRA was not different. Our results show the possibility, to stimulate renin secretion despite blockade of beta receptors by propranolol or practolol, respectively."} {"id": "PMID:175432", "title": "Gastric mucosal blood flow and pepsin secretion in dogs--stimulation by 13-nle-motilin.", "content": "In response to graded doses of intravenous 13-norleucine-motilin (13-nle-motilin)--a synthetic analogue of motilin and biologically equivalent to the natural polypeptide-, gastric mucosal blood flow (GMBF) in canine vagally denervated fundic pouches was studied using the aminopyrine clearance technique. As 13-nle-motilin did not exert any detectable effect on gastric secretion of hydrogen ions, intraluminal instillation of 160 mM HCl was used to provide a pH gradient allowing aminopyrine to move into the pouch lumen. With increasing doses of 13-nle-motilin, GMBF increased to 148% of control values; pepsin secretion - due to augmented pepsin concentration - rose concomitantly. Enhanced pepsin secretion was not accompanied by an increase in cyclic 3',5'-adenosine monophosphate secretion.", "contents": "Gastric mucosal blood flow and pepsin secretion in dogs--stimulation by 13-nle-motilin. In response to graded doses of intravenous 13-norleucine-motilin (13-nle-motilin)--a synthetic analogue of motilin and biologically equivalent to the natural polypeptide-, gastric mucosal blood flow (GMBF) in canine vagally denervated fundic pouches was studied using the aminopyrine clearance technique. As 13-nle-motilin did not exert any detectable effect on gastric secretion of hydrogen ions, intraluminal instillation of 160 mM HCl was used to provide a pH gradient allowing aminopyrine to move into the pouch lumen. With increasing doses of 13-nle-motilin, GMBF increased to 148% of control values; pepsin secretion - due to augmented pepsin concentration - rose concomitantly. Enhanced pepsin secretion was not accompanied by an increase in cyclic 3',5'-adenosine monophosphate secretion."} {"id": "PMID:175433", "title": "A rare case of megaloblastic anaemia caused by disturbances in the plasma cobalamin binding proteins in a patient with hepatocellular carcinoma.", "content": "A patient with hepatocellular carcinoma, megaloblastic anaemia and increased concentration of serum cobalamin is described. Plasma TC I was increased to 10,000 times the normal concentration, thus explaining the increased concentration of serum cobalamin and a false Schilling test. The increase in plasma TC I in concurrence with undetectable amounts of plasma TC II was a likely explanation for the anaemia. The electron microscopic picture of the hepatocellular carcinoma was in accordance with TC I being produced by the tumour cells.", "contents": "A rare case of megaloblastic anaemia caused by disturbances in the plasma cobalamin binding proteins in a patient with hepatocellular carcinoma. A patient with hepatocellular carcinoma, megaloblastic anaemia and increased concentration of serum cobalamin is described. Plasma TC I was increased to 10,000 times the normal concentration, thus explaining the increased concentration of serum cobalamin and a false Schilling test. The increase in plasma TC I in concurrence with undetectable amounts of plasma TC II was a likely explanation for the anaemia. The electron microscopic picture of the hepatocellular carcinoma was in accordance with TC I being produced by the tumour cells."} {"id": "PMID:175434", "title": "Search for uro-genital tract infections in patients with symptoms of prostatitis. Studies on aerobic and strictly anaerobic bacteria, mycoplasmas, fungi, trichomonads and viruses.", "content": "Seventy-nine patients with symptoms of nonacute prostatitis and 20 healthy volunteers were examined for uro-genital tract infection with bacteria, mycoplasmas, fungi, trichomonads and viruses. No differences in the results of the bacterial cultures were found between the patients and the controls. In only a few cases were established urinary tract pathogens found, but in no instance were these findings reproducible in later specimens. The cultures of the expressed prostatic fluids and the samples of semen gave no information of the occurrence of bacteria over and above that obtainable from examination of the urethral specimens. Significant bacteriuria was not found in any of the patients. Though Neisseria gonorrhoeae could not be isolated from any of the subjects, immunofluorescent studies revealed such organisms in seminal fluid in 8% of the patients. Nine of the patients had 1 to 3 years been considered successfully treated for gonorrhoea. Five of these nine patients were still found to harbour gonococci, as judged from the immunofluorescent studies. Corynebacterium vaginale was recovered in an equally low frequency (5%) from the patients and the volunteers. There was no significant difference in the incidence of T-mycoplasmas between the patients (46%) and the controls (35%), while Mycoplasma hominis was only found in the patients (10%). Trichomonas vaginalis could not be detected in wet smears of expressed prostatic fluid in any of the subjects, but could be cultured from one such specimen. Metacycline treatment (performed according the double blind cross-over technique) was studied for effects on the bacterial flora. In about 10% of the patients, an earlier not observed relative dominance of gram-negative rods was found on the cultures made after the therapy. Candida albicans was only isolated from the patients. It was found more often after (24%) than before the (15%) treatment. Complement-fixing antibodies to N. gonorrhoeae, cytomegalovirus and Chlamydia were found in 10, 19, and 33% of the patients, respectively. The corresponding figures for the healthy males were 0, 20 and 5%.", "contents": "Search for uro-genital tract infections in patients with symptoms of prostatitis. Studies on aerobic and strictly anaerobic bacteria, mycoplasmas, fungi, trichomonads and viruses. Seventy-nine patients with symptoms of nonacute prostatitis and 20 healthy volunteers were examined for uro-genital tract infection with bacteria, mycoplasmas, fungi, trichomonads and viruses. No differences in the results of the bacterial cultures were found between the patients and the controls. In only a few cases were established urinary tract pathogens found, but in no instance were these findings reproducible in later specimens. The cultures of the expressed prostatic fluids and the samples of semen gave no information of the occurrence of bacteria over and above that obtainable from examination of the urethral specimens. Significant bacteriuria was not found in any of the patients. Though Neisseria gonorrhoeae could not be isolated from any of the subjects, immunofluorescent studies revealed such organisms in seminal fluid in 8% of the patients. Nine of the patients had 1 to 3 years been considered successfully treated for gonorrhoea. Five of these nine patients were still found to harbour gonococci, as judged from the immunofluorescent studies. Corynebacterium vaginale was recovered in an equally low frequency (5%) from the patients and the volunteers. There was no significant difference in the incidence of T-mycoplasmas between the patients (46%) and the controls (35%), while Mycoplasma hominis was only found in the patients (10%). Trichomonas vaginalis could not be detected in wet smears of expressed prostatic fluid in any of the subjects, but could be cultured from one such specimen. Metacycline treatment (performed according the double blind cross-over technique) was studied for effects on the bacterial flora. In about 10% of the patients, an earlier not observed relative dominance of gram-negative rods was found on the cultures made after the therapy. Candida albicans was only isolated from the patients. It was found more often after (24%) than before the (15%) treatment. Complement-fixing antibodies to N. gonorrhoeae, cytomegalovirus and Chlamydia were found in 10, 19, and 33% of the patients, respectively. The corresponding figures for the healthy males were 0, 20 and 5%."} {"id": "PMID:175435", "title": "[Hyperlipoproteinemia in liver diseases].", "content": "Disorders of liver function frequently lead to raised plasma lipid values. The methods for analyzing plasma lipids and lipoproteins developed in recent years have yielded a great deal of data. This information provides new insights into the interrelationships of these disorders and are furthermore important in differential diagnosis of jaundice. An abnormal lipoprotein (LP-X) has been isolated from the plasma of patients with intra- or extrahepatic cholestasis, and a simple and sensitive method of demonstrating this lipoprotein has subsequently been developed. This parameter is today the surest clinico-chemical test for excluding or demonstrating cholestasis, triglyceride-rich lipoproteins accumulate in the plasma due to lack of lipase. This leads to hypertriglyceridemia. The disappearance of pre-beta and alpha-lipoprotein bands in agarose gel electrophoresis, which is a most frequent sign of severe liver damage (irrespective of its origin) is probably caused by a defective lipoprotein A. The capacity of lipoprotein A to bind certain lipid fractions is reduced or abolished. By no means all the mechanisms leading to structural changes in plasma lipoproteins and hyperlipoproteinemia in disorders of liver function are known at present. However, new findings emphasize the central role played by the liver in synthesis and degradation of plasma lipoproteins.", "contents": "[Hyperlipoproteinemia in liver diseases]. Disorders of liver function frequently lead to raised plasma lipid values. The methods for analyzing plasma lipids and lipoproteins developed in recent years have yielded a great deal of data. This information provides new insights into the interrelationships of these disorders and are furthermore important in differential diagnosis of jaundice. An abnormal lipoprotein (LP-X) has been isolated from the plasma of patients with intra- or extrahepatic cholestasis, and a simple and sensitive method of demonstrating this lipoprotein has subsequently been developed. This parameter is today the surest clinico-chemical test for excluding or demonstrating cholestasis, triglyceride-rich lipoproteins accumulate in the plasma due to lack of lipase. This leads to hypertriglyceridemia. The disappearance of pre-beta and alpha-lipoprotein bands in agarose gel electrophoresis, which is a most frequent sign of severe liver damage (irrespective of its origin) is probably caused by a defective lipoprotein A. The capacity of lipoprotein A to bind certain lipid fractions is reduced or abolished. By no means all the mechanisms leading to structural changes in plasma lipoproteins and hyperlipoproteinemia in disorders of liver function are known at present. However, new findings emphasize the central role played by the liver in synthesis and degradation of plasma lipoproteins."} {"id": "PMID:175436", "title": "[The after-care of tumor patients in radiotherapy].", "content": "A report is presented on the organization and goals of consultative outpatient follow-up of patients with irradiated tumors by the radiotherapeutic oncologist in a radiation therapy clinic. Organization involves a close working relationship with the referring physician and routine patient checkups at regular intervals after radiation therapy. The goals of the follow-up program include detection and treatment of irradiation-induced early and late alterations of normal tissue, assessment of therapeutic results, early recognition of recurrences, metastases and/or additional tumors and initiation of therapy of these. For these reasons standardized follow-up examinations are required. These must be adapted to the type of tumor and supplemented with the usually expensive and time-consuming tumor workup only where there is suspicion of tumor progression or if problems of differential diagnosis arise.", "contents": "[The after-care of tumor patients in radiotherapy]. A report is presented on the organization and goals of consultative outpatient follow-up of patients with irradiated tumors by the radiotherapeutic oncologist in a radiation therapy clinic. Organization involves a close working relationship with the referring physician and routine patient checkups at regular intervals after radiation therapy. The goals of the follow-up program include detection and treatment of irradiation-induced early and late alterations of normal tissue, assessment of therapeutic results, early recognition of recurrences, metastases and/or additional tumors and initiation of therapy of these. For these reasons standardized follow-up examinations are required. These must be adapted to the type of tumor and supplemented with the usually expensive and time-consuming tumor workup only where there is suspicion of tumor progression or if problems of differential diagnosis arise."} {"id": "PMID:175437", "title": "[The diagnosis of liver metastases and primary hepatomas by means of scintigraphy, laparoscopy and laparotomy].", "content": "To evaluate the presence or absence of hepatic metastases or primary hepatoma 106 patients were examined by liver scintigram as well as laparoscopy or laparotomy. A definite diagnosis was established in all patients by histology, autopsy or observation of clinical course for at least one year. Only scintigrams resulted in false positive diagnosis (in 5%). False negative diagnoses were obtained in 29% of laparoscopies and in 36% of scintigrams when evaluated routinely with knowledge of the clinical findings and laboratory examinations. Analysis of the same scintigrams by an experienced examiner without knowledge of the clinical findings lowered the proportion of false negative scintigrams to 12%. In 5 patients with liver metastases or hepatoma coexisting in liver cirrhosis or advanced chronic liver congestion, both methods of examination gave false negative results.", "contents": "[The diagnosis of liver metastases and primary hepatomas by means of scintigraphy, laparoscopy and laparotomy]. To evaluate the presence or absence of hepatic metastases or primary hepatoma 106 patients were examined by liver scintigram as well as laparoscopy or laparotomy. A definite diagnosis was established in all patients by histology, autopsy or observation of clinical course for at least one year. Only scintigrams resulted in false positive diagnosis (in 5%). False negative diagnoses were obtained in 29% of laparoscopies and in 36% of scintigrams when evaluated routinely with knowledge of the clinical findings and laboratory examinations. Analysis of the same scintigrams by an experienced examiner without knowledge of the clinical findings lowered the proportion of false negative scintigrams to 12%. In 5 patients with liver metastases or hepatoma coexisting in liver cirrhosis or advanced chronic liver congestion, both methods of examination gave false negative results."} {"id": "PMID:175438", "title": "[Proceedings: Clinical presentations in nephrology].", "content": "Four clinical cases are presented: (a) cured systemic lupus erythematosus, fracture of the odontoid process of the axis; (b) renovascular stenosis following renal transplant; dissecting aneurysm of aorta, consolidated for the last 3 years; (c) rejection glomerulonephritis following renal transplant; (d) unusual complications in a patient of intermittent hemodialysis for the last 8 years.", "contents": "[Proceedings: Clinical presentations in nephrology]. Four clinical cases are presented: (a) cured systemic lupus erythematosus, fracture of the odontoid process of the axis; (b) renovascular stenosis following renal transplant; dissecting aneurysm of aorta, consolidated for the last 3 years; (c) rejection glomerulonephritis following renal transplant; (d) unusual complications in a patient of intermittent hemodialysis for the last 8 years."} {"id": "PMID:175439", "title": "[The current state of masculine contraception].", "content": "The present state of male contraception is reviewed with reference to pharmacological methods only. Since spermatogenesis is the result of a long chain of endocrine mechanisms starting in the hypothalamus, any review of contraceptive techniques must follow these physiological links. Spermatogenesis itself involves different stages and each of them can be a target for pharmacological compounds. Although no drug is currently available that offers all the necessary guarantees required of a contraceptive, interesting interconnections have nevertheless emerged. In consequence there are grounds for moderate optimism as to the availability of a male contraceptive in the coming years.", "contents": "[The current state of masculine contraception]. The present state of male contraception is reviewed with reference to pharmacological methods only. Since spermatogenesis is the result of a long chain of endocrine mechanisms starting in the hypothalamus, any review of contraceptive techniques must follow these physiological links. Spermatogenesis itself involves different stages and each of them can be a target for pharmacological compounds. Although no drug is currently available that offers all the necessary guarantees required of a contraceptive, interesting interconnections have nevertheless emerged. In consequence there are grounds for moderate optimism as to the availability of a male contraceptive in the coming years."} {"id": "PMID:175440", "title": "Behaviorally evoked hippocampal theta waves: a cholinergic response.", "content": "Forced running in a treadmill results in the instantaneous appearance of a synchronous electroencephalographic pattern in the dorsal hippocampus of the rat. A similar bioelectric response in the absence of movement is induced by physostigmine. Both responses are blocked with scopolamine. Lesions of the medial septal nucleus abolish hippocampal theta waves induced by forced running or physostigmine.", "contents": "Behaviorally evoked hippocampal theta waves: a cholinergic response. Forced running in a treadmill results in the instantaneous appearance of a synchronous electroencephalographic pattern in the dorsal hippocampus of the rat. A similar bioelectric response in the absence of movement is induced by physostigmine. Both responses are blocked with scopolamine. Lesions of the medial septal nucleus abolish hippocampal theta waves induced by forced running or physostigmine."} {"id": "PMID:175441", "title": "Glycerol phosphate shuttle in virus-transformed cells in culture.", "content": "The glycerol phosphate shuttle is shown not only to be present and functional in virus-transformed cells, but its level is higher than in normal cells in culture. The increased aerobic glycolysis that has been demonstrated for these cells after transformation, therefore, is not due to an impairment of hydrogen transfer pathways.", "contents": "Glycerol phosphate shuttle in virus-transformed cells in culture. The glycerol phosphate shuttle is shown not only to be present and functional in virus-transformed cells, but its level is higher than in normal cells in culture. The increased aerobic glycolysis that has been demonstrated for these cells after transformation, therefore, is not due to an impairment of hydrogen transfer pathways."} {"id": "PMID:175442", "title": "Estrogen receptor in the mammalian liver.", "content": "The cytosol from livers of adult female mammals contains [3H]estradiol-binding proteins that can translocate to the nucleus and attach to chromatin. In comparison to the prepubescent rat, adults have higher estrogen binding in the liver and greater increases in plasma renin substrate after administration of estrogen. The protein in the liver which binds estrogen may be an estrogen receptor involved in modulating hepatic synthesis of selective plasma proteins.", "contents": "Estrogen receptor in the mammalian liver. The cytosol from livers of adult female mammals contains [3H]estradiol-binding proteins that can translocate to the nucleus and attach to chromatin. In comparison to the prepubescent rat, adults have higher estrogen binding in the liver and greater increases in plasma renin substrate after administration of estrogen. The protein in the liver which binds estrogen may be an estrogen receptor involved in modulating hepatic synthesis of selective plasma proteins."} {"id": "PMID:175443", "title": "Photoreceptor-bipolar cell transmission in the perfused retina eyecup of the mudpuppy.", "content": "The hypothesis that a synaptic transmitter is released by photoreceptors in the dark is supported by experiments in which cobalt was used as a synaptic blocking agent, while intracellular recordings of receptors and neurons that are directly postsynaptic to receptors were maintained. In the dark the depolarizing bipolars are hyperpolarized, whereas the hyperpolarizing bipolars are depolarized.", "contents": "Photoreceptor-bipolar cell transmission in the perfused retina eyecup of the mudpuppy. The hypothesis that a synaptic transmitter is released by photoreceptors in the dark is supported by experiments in which cobalt was used as a synaptic blocking agent, while intracellular recordings of receptors and neurons that are directly postsynaptic to receptors were maintained. In the dark the depolarizing bipolars are hyperpolarized, whereas the hyperpolarizing bipolars are depolarized."} {"id": "PMID:175444", "title": "Angiotensin-converting enzyme: vascular endothelial localization.", "content": "Fluorescein-labeled antibody to rabbit pulmonary angiotensin-converting enzyme localized in the vascular endothelium of rabbit lung, liver, adrenal cortex, pancreas, kidney, and spleen. Epithelial cells of the renal proximal tubules were the only parenchymal cells among the organs studied that demonstrated immunoreactivity.", "contents": "Angiotensin-converting enzyme: vascular endothelial localization. Fluorescein-labeled antibody to rabbit pulmonary angiotensin-converting enzyme localized in the vascular endothelium of rabbit lung, liver, adrenal cortex, pancreas, kidney, and spleen. Epithelial cells of the renal proximal tubules were the only parenchymal cells among the organs studied that demonstrated immunoreactivity."} {"id": "PMID:175446", "title": "[Bronchopulmonary aspergilloma in children and bronchogenic cyst. A new case].", "content": "The authors report a new case of aspergilloma developing in an intra-pulmonary bronchogenic cyst in a girl aged 10 years. A cure was obtained after surgical excision. The possibility of serious complications, such as hemoptysis, abscess formation and spread of the aspergillus, has two consequences; the first is the utility of regular supervision of any intra-pulmonary air cavity and, eventually, surgical removal. The second is the necessity of operation as soon as the diagnosis of aspergilloma has been made.", "contents": "[Bronchopulmonary aspergilloma in children and bronchogenic cyst. A new case]. The authors report a new case of aspergilloma developing in an intra-pulmonary bronchogenic cyst in a girl aged 10 years. A cure was obtained after surgical excision. The possibility of serious complications, such as hemoptysis, abscess formation and spread of the aspergillus, has two consequences; the first is the utility of regular supervision of any intra-pulmonary air cavity and, eventually, surgical removal. The second is the necessity of operation as soon as the diagnosis of aspergilloma has been made."} {"id": "PMID:175447", "title": "[Malignant lymphopathy and breast cancer (apropos of 3 cases)].", "content": "Two cases of Hodgkin's disease were associated with a breast tumor after a remission of seven years. Conversely, another patient was affected by a mammary adenocarcinoma prior to the onset of an overt acute lymphoblastic leukemia in the same delay. These three observations focussed our attention upon the development of secondary neoplasias and the possible relationship between both types of disorders. In a period with extensive research on cancer etiology, it seemed interesting to discuss the role of several factors: genetic, therapeutic and/or immunological ones.", "contents": "[Malignant lymphopathy and breast cancer (apropos of 3 cases)]. Two cases of Hodgkin's disease were associated with a breast tumor after a remission of seven years. Conversely, another patient was affected by a mammary adenocarcinoma prior to the onset of an overt acute lymphoblastic leukemia in the same delay. These three observations focussed our attention upon the development of secondary neoplasias and the possible relationship between both types of disorders. In a period with extensive research on cancer etiology, it seemed interesting to discuss the role of several factors: genetic, therapeutic and/or immunological ones."} {"id": "PMID:175448", "title": "[Prostaglandins and reproduction].", "content": "The prostaglandins probably play an important role in the physiology of reproduction. In women as in men, they intervene at several levels. At the level of the ovary, the prostaglandins E may be modulators of the action of gonadostimulin on ovarian hormonogenesis, in close relationship with cyclic AMP and, furthermore, represent an important biochemical intermediate stage in the mechanism of ovulation. F2 prostaglandin, F2 alpha, on the other hand, represents in numerous animals, but not in women, a luteolytic factor of uterine origin. At the level of the hypothalamopituitary axis, E prostaglandins may modulate hypothalamic neuro-secretion and to a lesser degree, the liberation of pituitary stimulins, and thus intervene in gonadotropic function. At the level of the female genital tract, prostaglandins may influence uterine and tubal motility. It is perhaps by this latter effect that the very large quantities of seminal prostaglandin influence the process of fertilisation.", "contents": "[Prostaglandins and reproduction]. The prostaglandins probably play an important role in the physiology of reproduction. In women as in men, they intervene at several levels. At the level of the ovary, the prostaglandins E may be modulators of the action of gonadostimulin on ovarian hormonogenesis, in close relationship with cyclic AMP and, furthermore, represent an important biochemical intermediate stage in the mechanism of ovulation. F2 prostaglandin, F2 alpha, on the other hand, represents in numerous animals, but not in women, a luteolytic factor of uterine origin. At the level of the hypothalamopituitary axis, E prostaglandins may modulate hypothalamic neuro-secretion and to a lesser degree, the liberation of pituitary stimulins, and thus intervene in gonadotropic function. At the level of the female genital tract, prostaglandins may influence uterine and tubal motility. It is perhaps by this latter effect that the very large quantities of seminal prostaglandin influence the process of fertilisation."} {"id": "PMID:175452", "title": "[Granulopoiesis and its regulation].", "content": "The neutrophil granulocytes are derived, in the present state of our knowledge, from a hemocytoblast identical with that of the other blood cells, defined by its power to form in vivo clones of multiple composition, defining their characteristic of totipotential undifferentiated cell. The way in which the clone-forming cell evolves in vivo towards granulopoiesis, depends on a genetic factor, phenomena of derepression and an extrinsic factor, the origin of which is probably cellular. Differentiation of the hemocytoblast leads to a cell, the destiny of which is then fixed, which may then form clones in vitro in semi-solid medium (clone-forming cell in vitro or CFC). This cell is definitely a true entity. A humoral factor of macrophage origin intervenes to ensure granulopoiesis in vivo (clone-stimulating factor CSF3. The phenomena which regulate this granulopoiesis then cause to intervene various biochemical forms of this clone-stimulating factor and an inhibitor, the reality of which is not yet definitely demonstrated in vivo. Laboratory animals and cell culture of human normal and leukemic granular cells now supplies experimental models which permit studies of the granular differentiation of the hemocytoblast completed by kinetic studies in vivo to make rapid progress, especially in our knowledge of the human leukemic process.", "contents": "[Granulopoiesis and its regulation]. The neutrophil granulocytes are derived, in the present state of our knowledge, from a hemocytoblast identical with that of the other blood cells, defined by its power to form in vivo clones of multiple composition, defining their characteristic of totipotential undifferentiated cell. The way in which the clone-forming cell evolves in vivo towards granulopoiesis, depends on a genetic factor, phenomena of derepression and an extrinsic factor, the origin of which is probably cellular. Differentiation of the hemocytoblast leads to a cell, the destiny of which is then fixed, which may then form clones in vitro in semi-solid medium (clone-forming cell in vitro or CFC). This cell is definitely a true entity. A humoral factor of macrophage origin intervenes to ensure granulopoiesis in vivo (clone-stimulating factor CSF3. The phenomena which regulate this granulopoiesis then cause to intervene various biochemical forms of this clone-stimulating factor and an inhibitor, the reality of which is not yet definitely demonstrated in vivo. Laboratory animals and cell culture of human normal and leukemic granular cells now supplies experimental models which permit studies of the granular differentiation of the hemocytoblast completed by kinetic studies in vivo to make rapid progress, especially in our knowledge of the human leukemic process."} {"id": "PMID:175453", "title": "[Kinetics of polynuclear cells].", "content": "Polymorphonuclear leukocytosis and granulopenia in infectious diseases have been studied for several years, either by intravascular kinetics of the polymorphs labelled previously in vitro, or by isotopic labelling in vivo and autoradiography of the bone marrow, using medullary kinetic study of granulopoiesis. Polymorpho-nuclear leukocytosis is usually due to an increased production and a relative mobilisation of reserves. Leukopenia may be due to various mechanisms, but there does not seem to be any qualitative disorder of circulating polymorphonuclear leukocytes with corpuscular hyperdestruction nor any abnormalities of multiplication of the bone marrow nor of maturation. On the other hand, one frequently finds abnormalities of distribution between the marginal and circulating compartments, increased extracorpuscular destruction, reduction in production due to reduction in absolute number or differentiation of the granulopoietic parent cells.", "contents": "[Kinetics of polynuclear cells]. Polymorphonuclear leukocytosis and granulopenia in infectious diseases have been studied for several years, either by intravascular kinetics of the polymorphs labelled previously in vitro, or by isotopic labelling in vivo and autoradiography of the bone marrow, using medullary kinetic study of granulopoiesis. Polymorpho-nuclear leukocytosis is usually due to an increased production and a relative mobilisation of reserves. Leukopenia may be due to various mechanisms, but there does not seem to be any qualitative disorder of circulating polymorphonuclear leukocytes with corpuscular hyperdestruction nor any abnormalities of multiplication of the bone marrow nor of maturation. On the other hand, one frequently finds abnormalities of distribution between the marginal and circulating compartments, increased extracorpuscular destruction, reduction in production due to reduction in absolute number or differentiation of the granulopoietic parent cells."} {"id": "PMID:175454", "title": "[Leukocytosis and polynucleosis in infectious disease].", "content": "During bacterial infections, the intensity of the polymorphonuclear leukocytosis depends on the bacterium but also on the mechanism and extent of the infection. Polymorphonuclear leukocytosis is greater during pyogenic and anaerobic infections. It is due to deep suppuration, septicemia of thrombophlebitic origin, acute endocarditis, purulent meningitis and pneumonia. The increase in the number of polymorphonuclear cells is, on the other hand, less marked in sub-acute bacterial endocarditis. Apart from bacterial infections, a polymorphonuclear leukocytosis is common in inflammatory disease, such as tissue necrosis and several malignant diseases. It may also be due to drug allergy.", "contents": "[Leukocytosis and polynucleosis in infectious disease]. During bacterial infections, the intensity of the polymorphonuclear leukocytosis depends on the bacterium but also on the mechanism and extent of the infection. Polymorphonuclear leukocytosis is greater during pyogenic and anaerobic infections. It is due to deep suppuration, septicemia of thrombophlebitic origin, acute endocarditis, purulent meningitis and pneumonia. The increase in the number of polymorphonuclear cells is, on the other hand, less marked in sub-acute bacterial endocarditis. Apart from bacterial infections, a polymorphonuclear leukocytosis is common in inflammatory disease, such as tissue necrosis and several malignant diseases. It may also be due to drug allergy."} {"id": "PMID:175455", "title": "[Granulopenia of infectious origin].", "content": "Among the various infectious and parasitic disease liable to produce granulopenia, the authors selected certain diseases which represented their personal experience. Classically, leukopenia may occur during typhoid fever, but was not present in all of the series of 114 adults they observed with this disease. It only occurs after antibiotic treatment (Thiamphenicol in the majority of cases). During acute brucellosis (188 cases studied) granulopenia was constant. It occurs early and is lasting. It reappears during septicemic relapse. Leukopenia is corrected during treatment by tetracycline antibiotics. Neutropenia during disease is frequent but usually labile. This characteristic explains why there was no granulopenia in 90 cases of mumps and 64 cases of chickenpox. Finally, during Kala Azar, 8 cases confirmed certain already well known data: the considerable reduction in granulocytes but also anemia and thrombocytopenia.", "contents": "[Granulopenia of infectious origin]. Among the various infectious and parasitic disease liable to produce granulopenia, the authors selected certain diseases which represented their personal experience. Classically, leukopenia may occur during typhoid fever, but was not present in all of the series of 114 adults they observed with this disease. It only occurs after antibiotic treatment (Thiamphenicol in the majority of cases). During acute brucellosis (188 cases studied) granulopenia was constant. It occurs early and is lasting. It reappears during septicemic relapse. Leukopenia is corrected during treatment by tetracycline antibiotics. Neutropenia during disease is frequent but usually labile. This characteristic explains why there was no granulopenia in 90 cases of mumps and 64 cases of chickenpox. Finally, during Kala Azar, 8 cases confirmed certain already well known data: the considerable reduction in granulocytes but also anemia and thrombocytopenia."} {"id": "PMID:175456", "title": "[Infections in agranulocytosis and their treatment].", "content": "A quantitative deficiency in polymorpho-nuclear leukocytes, due to aplastic anemia, exposes to infection. The risk is all the greater when the neutropenia is more marked and more lasting. The infections have a different distribution from that commonly observed in normal subjects. There is little inflammatory reaction, no pus formation and bacterial multiplication invades the parenchyma and may create necrosis due to arteriolar obstruction. The prognosis is very bad. For example, pulmonary infections in acute leukemia of adults, have a mortality greater than 75%. Antibiotic treatment and leukocyte transfusions give disappointing results. The prevention of infections has permitted spectacular progress. Nevertheless, the long-term prognosis is not linked to the infection itself, but to the sub-jacent disease responsible for the agranulocytosis. The infections become cured in transient toxic aplasia and in leukemia where chemotherapy permits one to obtain a remission. The infections remain fatal whatever the treatment used if the medullary aplasia is not curable.", "contents": "[Infections in agranulocytosis and their treatment]. A quantitative deficiency in polymorpho-nuclear leukocytes, due to aplastic anemia, exposes to infection. The risk is all the greater when the neutropenia is more marked and more lasting. The infections have a different distribution from that commonly observed in normal subjects. There is little inflammatory reaction, no pus formation and bacterial multiplication invades the parenchyma and may create necrosis due to arteriolar obstruction. The prognosis is very bad. For example, pulmonary infections in acute leukemia of adults, have a mortality greater than 75%. Antibiotic treatment and leukocyte transfusions give disappointing results. The prevention of infections has permitted spectacular progress. Nevertheless, the long-term prognosis is not linked to the infection itself, but to the sub-jacent disease responsible for the agranulocytosis. The infections become cured in transient toxic aplasia and in leukemia where chemotherapy permits one to obtain a remission. The infections remain fatal whatever the treatment used if the medullary aplasia is not curable."} {"id": "PMID:175457", "title": "[Massive ascites in pancreatitis. Review apropos of 10 personal cases].", "content": "Massive ascites is are complication, but not exceptional, in pancreatitis. In a series of ten personal cases and a review of one hundred cases in the world literature, the authors attempt to define the main pathological and clinical characteristics of this disease and the best treatment. Ascites may follow abdominal trauma, involving the pancreas, sometimes it occurs during known chronic pancreatitis, often it is the first sign of pancreatic disease, whether acute or chronic. High levels of pancreatic enzymes in the ascitic fluid are the main factor in diagnosis of pancreatic ascites. The mechanism of formation of the ascites is loss of pancreatic fluid into the peritoneal cavity owing to a breach in the pancreas, the presence of enzyme-rich fluid, causing secondarily \"chemical\" peritonitis. Paracentesis abdominis or drainage of the fluid during exploratory laparotomy, permits one to obtain in certain cases, a cure of the ascites, but surgical drainage by an anastomosis between the pancreatic cyst and the digestive tract (pancreatico-digestive anastomosis), has the advantage of ensuring treatment of the ascites and of the responsible pancreatic disease.", "contents": "[Massive ascites in pancreatitis. Review apropos of 10 personal cases]. Massive ascites is are complication, but not exceptional, in pancreatitis. In a series of ten personal cases and a review of one hundred cases in the world literature, the authors attempt to define the main pathological and clinical characteristics of this disease and the best treatment. Ascites may follow abdominal trauma, involving the pancreas, sometimes it occurs during known chronic pancreatitis, often it is the first sign of pancreatic disease, whether acute or chronic. High levels of pancreatic enzymes in the ascitic fluid are the main factor in diagnosis of pancreatic ascites. The mechanism of formation of the ascites is loss of pancreatic fluid into the peritoneal cavity owing to a breach in the pancreas, the presence of enzyme-rich fluid, causing secondarily \"chemical\" peritonitis. Paracentesis abdominis or drainage of the fluid during exploratory laparotomy, permits one to obtain in certain cases, a cure of the ascites, but surgical drainage by an anastomosis between the pancreatic cyst and the digestive tract (pancreatico-digestive anastomosis), has the advantage of ensuring treatment of the ascites and of the responsible pancreatic disease."} {"id": "PMID:175458", "title": "[Evaluation of the involvement of the spleen in Hodgkin's disease].", "content": "In the light of personal data and 60 cases in the literature, the authors attempt to evaluate the risk of splenic involvement during Hodgkin's disease. Neither clinical examination nor scintiscanning of the spleen, permit one with sufficient security to recognise splenic involvement. Study of the context reveals, on the contrary, that the following factors contribute to the splenic risk: --Signs of evolutivity: their presence implies splenic involvement in 63% of cases; --the histological type of the frequency of the splenic involvement increases from type 1 (38%) to type 4 (61%); --the distribution of the lymph nodes above the diaphragm, the spleen is involved in 66% of forms with cervical and mediastinal and axillary lymph node involvement, 56% in forms with cervical and axillary nodes alone and 24% in forms with cervical and mediastinal nodes alone; --the data obtained by lymphography, as 89% of patients with lumboaortic gland involvement, also had invasion of the spleen. There may be errors of interpretation of lymphography, depending on the series, of from 6 to 25%. Thus, assessment of the risk of splenic involvement in Hodgkin's disease is carried out less on the splenic signs themselves, than on the clinical, laboratory, histological and radiological context.", "contents": "[Evaluation of the involvement of the spleen in Hodgkin's disease]. In the light of personal data and 60 cases in the literature, the authors attempt to evaluate the risk of splenic involvement during Hodgkin's disease. Neither clinical examination nor scintiscanning of the spleen, permit one with sufficient security to recognise splenic involvement. Study of the context reveals, on the contrary, that the following factors contribute to the splenic risk: --Signs of evolutivity: their presence implies splenic involvement in 63% of cases; --the histological type of the frequency of the splenic involvement increases from type 1 (38%) to type 4 (61%); --the distribution of the lymph nodes above the diaphragm, the spleen is involved in 66% of forms with cervical and mediastinal and axillary lymph node involvement, 56% in forms with cervical and axillary nodes alone and 24% in forms with cervical and mediastinal nodes alone; --the data obtained by lymphography, as 89% of patients with lumboaortic gland involvement, also had invasion of the spleen. There may be errors of interpretation of lymphography, depending on the series, of from 6 to 25%. Thus, assessment of the risk of splenic involvement in Hodgkin's disease is carried out less on the splenic signs themselves, than on the clinical, laboratory, histological and radiological context."} {"id": "PMID:175459", "title": "[Detection of anti-DNA antibodies by electroimmunodiffusion. Comparison of the results with the study of antinuclear factors by immunofluorescence].", "content": "The detection of anti-DNA antibodies was carried out by the electroimmunodiffusion method. The results were compared to those of the immunofluorescent method for anti-nuclear factors. Positive results were obtained with the electroimmunodiffusion method in 86% of the lupus erythematosus cases, 77% of the sero-positive rhumatoid polyarthritis cases and 67% of the scleroderma cases. They are comparable to those obtained by other methods. The electroimmunodiffusion method allowed in 3 out of 54 sera to defect anti-DNA antibodies although no anti-nuclear factor was found.", "contents": "[Detection of anti-DNA antibodies by electroimmunodiffusion. Comparison of the results with the study of antinuclear factors by immunofluorescence]. The detection of anti-DNA antibodies was carried out by the electroimmunodiffusion method. The results were compared to those of the immunofluorescent method for anti-nuclear factors. Positive results were obtained with the electroimmunodiffusion method in 86% of the lupus erythematosus cases, 77% of the sero-positive rhumatoid polyarthritis cases and 67% of the scleroderma cases. They are comparable to those obtained by other methods. The electroimmunodiffusion method allowed in 3 out of 54 sera to defect anti-DNA antibodies although no anti-nuclear factor was found."} {"id": "PMID:175460", "title": "[Unilateral renal atrophy].", "content": "The authors report 45 cases of unilateral renal atrophy. The circumstances of discovery are related to the urological symptoms: pain, hematuria, pyuria. On the other hand, hypertension is rarely the reason for consultation. Women are more affected than men. Intravenous urography, retrograde cystography and arteriography are essential examinations to collect information concerning the etiology. Dynamic scintiscanning with measurement of the percentage of isotope fixed on the kidneys, has the advantage of permitting comparative evaluation of renal function on each side. In our study, obstruction of the urinary tract was more frequent than parenchymatous disease favoured by infection. Vascular abnormalities were rare. The etiological enquiry remained, however, negative in one third of cases. Surgical operation was necessary when a urological abnormality was the cause of persistence of severe symptoms. On the other hand, removal of the atrophic kidney does not seem to us advisable when decided simply to relieve hypertension. The latter point is particularly discussed.", "contents": "[Unilateral renal atrophy]. The authors report 45 cases of unilateral renal atrophy. The circumstances of discovery are related to the urological symptoms: pain, hematuria, pyuria. On the other hand, hypertension is rarely the reason for consultation. Women are more affected than men. Intravenous urography, retrograde cystography and arteriography are essential examinations to collect information concerning the etiology. Dynamic scintiscanning with measurement of the percentage of isotope fixed on the kidneys, has the advantage of permitting comparative evaluation of renal function on each side. In our study, obstruction of the urinary tract was more frequent than parenchymatous disease favoured by infection. Vascular abnormalities were rare. The etiological enquiry remained, however, negative in one third of cases. Surgical operation was necessary when a urological abnormality was the cause of persistence of severe symptoms. On the other hand, removal of the atrophic kidney does not seem to us advisable when decided simply to relieve hypertension. The latter point is particularly discussed."} {"id": "PMID:175463", "title": "[Effect of rest on the course of viral hepatitis].", "content": "Discussions having lately raised the importance of rest in the treatment of viral hepatitis the authors report some studies made on the subject. They take into account 3 personal unpublished statistics analyzing the role of effort at 3 different stages -- in the acute phase, during convalescence and as an eventual factor producing aggravation. Although their results appear to be in contradiction with those found in American studies the authors show that the importance of rest in the initial phase is unanimously recognized and that there is no statistical evidence that such a prescription should be given up before the normalization of the main biological parameters. Furthermore though it is statistically proved that a certain activity between the 30th and 60th day does not affect the later course of the disease yet there is no element which allows to authorize the patient to resume his normal professionnal activity before the 60th day. Finally the lack of controlled studies does not allow any precise determination of the impact of effort in the determinism of an eventual aggravation. However according to the authors' experience physical tiredness can legitimately be suspected to have produced this aggravation in 47.06 % of cases of a secondarily aggravated hepatitis.", "contents": "[Effect of rest on the course of viral hepatitis]. Discussions having lately raised the importance of rest in the treatment of viral hepatitis the authors report some studies made on the subject. They take into account 3 personal unpublished statistics analyzing the role of effort at 3 different stages -- in the acute phase, during convalescence and as an eventual factor producing aggravation. Although their results appear to be in contradiction with those found in American studies the authors show that the importance of rest in the initial phase is unanimously recognized and that there is no statistical evidence that such a prescription should be given up before the normalization of the main biological parameters. Furthermore though it is statistically proved that a certain activity between the 30th and 60th day does not affect the later course of the disease yet there is no element which allows to authorize the patient to resume his normal professionnal activity before the 60th day. Finally the lack of controlled studies does not allow any precise determination of the impact of effort in the determinism of an eventual aggravation. However according to the authors' experience physical tiredness can legitimately be suspected to have produced this aggravation in 47.06 % of cases of a secondarily aggravated hepatitis."} {"id": "PMID:175464", "title": "[Orthostatic hypotension in the aged. Systematic exploration in 400 persons].", "content": "The authors study the adaptation of the blood pressure to changes in posture in 400 people, and studied the world literature on the subject. They found that postural hypotension in the elderly is quite different from that in young adults. A full study is difficult and the response to changes in posture are inconstant, this it is only possible to take into consideration changes in systolic blood pressure, and one should not neglect falls in blood pressure of low amplitude. This definition, once accepted, postural hypotension in the elderly is a frequent phenomenon which gives complex symptoms owing to the intrication of vascular disturbances and lesions of the central nervous system. Among the numerous permanent or occasional causes, more particularly those due to drugs, the role of hypovolemia seems to be of importance in orthostatic hypotension and should be sought as a routine.", "contents": "[Orthostatic hypotension in the aged. Systematic exploration in 400 persons]. The authors study the adaptation of the blood pressure to changes in posture in 400 people, and studied the world literature on the subject. They found that postural hypotension in the elderly is quite different from that in young adults. A full study is difficult and the response to changes in posture are inconstant, this it is only possible to take into consideration changes in systolic blood pressure, and one should not neglect falls in blood pressure of low amplitude. This definition, once accepted, postural hypotension in the elderly is a frequent phenomenon which gives complex symptoms owing to the intrication of vascular disturbances and lesions of the central nervous system. Among the numerous permanent or occasional causes, more particularly those due to drugs, the role of hypovolemia seems to be of importance in orthostatic hypotension and should be sought as a routine."} {"id": "PMID:175465", "title": "[Alpha 1 antitrypsin deficiency and liver diseases].", "content": "Alpha-1 antitrypsin is mainly responsible for the inhibitory power with regard to serum of numerous enzymes, in particular, trypsin. Alpha-1 antitrypsin deficiency is linked to pulmonary and hepatic disease. The special characteristic constantly found during liver disease, associated with alpha-1 antitrypsin deficiency, is the existence of intra-cytoplasmic globules within the hepatocytes due to accumulation of alpha-1 antitrypsin. This latter enzyme differs chemically from serum alpha-1 antitrypsin.", "contents": "[Alpha 1 antitrypsin deficiency and liver diseases]. Alpha-1 antitrypsin is mainly responsible for the inhibitory power with regard to serum of numerous enzymes, in particular, trypsin. Alpha-1 antitrypsin deficiency is linked to pulmonary and hepatic disease. The special characteristic constantly found during liver disease, associated with alpha-1 antitrypsin deficiency, is the existence of intra-cytoplasmic globules within the hepatocytes due to accumulation of alpha-1 antitrypsin. This latter enzyme differs chemically from serum alpha-1 antitrypsin."} {"id": "PMID:175467", "title": "[Practical significance of HL-A groups in rheumatology].", "content": "Since 1972, several relations have been demonstrated between some HL-A antigens and some articular diseases. The W27 antigen frequency is highly increased in ankylosing spondylitis (88%) and in Reiter disease (78%) compared with controls (5%). In peripheral forms of psoriatic rheumatism, the W17 and HL-A13 antigens are more fr\u00e9quent (24% and 15%) than in healthy subjects (4% and 5%). In central forms of psoriatic rheumatism, there is a relation with W27 (48%) and still, we do not know if this association concerns only spondylitis or also sacro-ileitis. The HL-A typing may be useful for the diagnosis of some rheumatic diseases, when they present atypical appearances. W27 possesses a considerable value for the diagnosis of ankylosing spondylitis. The relation between W27 and ankylosing spondylitis is clearly stronger than that between Waaler-Rose reaction and rheumatoid arthritis.", "contents": "[Practical significance of HL-A groups in rheumatology]. Since 1972, several relations have been demonstrated between some HL-A antigens and some articular diseases. The W27 antigen frequency is highly increased in ankylosing spondylitis (88%) and in Reiter disease (78%) compared with controls (5%). In peripheral forms of psoriatic rheumatism, the W17 and HL-A13 antigens are more fr\u00e9quent (24% and 15%) than in healthy subjects (4% and 5%). In central forms of psoriatic rheumatism, there is a relation with W27 (48%) and still, we do not know if this association concerns only spondylitis or also sacro-ileitis. The HL-A typing may be useful for the diagnosis of some rheumatic diseases, when they present atypical appearances. W27 possesses a considerable value for the diagnosis of ankylosing spondylitis. The relation between W27 and ankylosing spondylitis is clearly stronger than that between Waaler-Rose reaction and rheumatoid arthritis."} {"id": "PMID:175468", "title": "[Intrahepatic cholestasis].", "content": "Intrahepatic cholestasis has become a very important aspect of liver disease. The author, in the light of electron microscopy and the theory of filtration-reabsorption of bile secretion proposes that the disease may be explained by obstructions situated at various levels of the inter-cellular spaces of the liver. This obstruction is functional at first, but is maintained by a duodeno-hepatic inhibitory reflex, the existence of which has been demonstrated by the author. In the light of facts and documents presented here, one may see that from Monneret until now, various authors have come very close to the true mechanism of this type of jaundice, each discovering some aspect of the truth.", "contents": "[Intrahepatic cholestasis]. Intrahepatic cholestasis has become a very important aspect of liver disease. The author, in the light of electron microscopy and the theory of filtration-reabsorption of bile secretion proposes that the disease may be explained by obstructions situated at various levels of the inter-cellular spaces of the liver. This obstruction is functional at first, but is maintained by a duodeno-hepatic inhibitory reflex, the existence of which has been demonstrated by the author. In the light of facts and documents presented here, one may see that from Monneret until now, various authors have come very close to the true mechanism of this type of jaundice, each discovering some aspect of the truth."} {"id": "PMID:175469", "title": "[Extensive bony condensation of the vertebrae in intervertebral disc degeneration. (Study of 25 cases)].", "content": "The authors report 25 cases of extensive bony condensation of the vertebrae due to degeneration of the intervertebral discs, giving on lateral XRay a dome-shaped or helmet-shaped appearance. 19 cases occurred in women. Two-thirds of the patients were aged between 35 and 55 years, with an average of 45 years. The lesions were lumbar in 21 patients. They affected in 20 cases two adjacent vertebrae. All the clinical, radiological, pathological and discographic findings, together with the course, confirmed the degenerative origin of these bony condensations, the pathogenesis of which is still not perfectly understood.", "contents": "[Extensive bony condensation of the vertebrae in intervertebral disc degeneration. (Study of 25 cases)]. The authors report 25 cases of extensive bony condensation of the vertebrae due to degeneration of the intervertebral discs, giving on lateral XRay a dome-shaped or helmet-shaped appearance. 19 cases occurred in women. Two-thirds of the patients were aged between 35 and 55 years, with an average of 45 years. The lesions were lumbar in 21 patients. They affected in 20 cases two adjacent vertebrae. All the clinical, radiological, pathological and discographic findings, together with the course, confirmed the degenerative origin of these bony condensations, the pathogenesis of which is still not perfectly understood."} {"id": "PMID:175470", "title": "[Idiopathic hemochromatosis and primary cancer of the liver].", "content": "In 74 patients admitted to hospital for primary hemochromatosis, the authors observed in 5 cases, the development of primary carcinoma of the liver. The frequency of this complication was definitely greater than in alcoholic or post-hepatitic cirrhosis, whether one considers patients in hospital or on autopsy. The best signs of malignant change are alterations in the surface of the liver and the development of hemorrhagic ascites. Using modern methods of clinical investigation, it is possible to make the diagnosis during the patient's life. Laparoscopy, permitting biopsy under direct vision, is the best investigation but it is not always possible. A search for alpha 1 foeto-protein was positive in one third of cases and the demonstration by hepatic arteriography of characteristic vascular abnormalities and, perhaps in future, information supplied by ultra-sonic echography, usually permit one to make the diagnosis. The course was fatal within a few months, and it seems that metastases and vascular spread are less frequent than in carcinoma developing on cirrhosis due to other causes.", "contents": "[Idiopathic hemochromatosis and primary cancer of the liver]. In 74 patients admitted to hospital for primary hemochromatosis, the authors observed in 5 cases, the development of primary carcinoma of the liver. The frequency of this complication was definitely greater than in alcoholic or post-hepatitic cirrhosis, whether one considers patients in hospital or on autopsy. The best signs of malignant change are alterations in the surface of the liver and the development of hemorrhagic ascites. Using modern methods of clinical investigation, it is possible to make the diagnosis during the patient's life. Laparoscopy, permitting biopsy under direct vision, is the best investigation but it is not always possible. A search for alpha 1 foeto-protein was positive in one third of cases and the demonstration by hepatic arteriography of characteristic vascular abnormalities and, perhaps in future, information supplied by ultra-sonic echography, usually permit one to make the diagnosis. The course was fatal within a few months, and it seems that metastases and vascular spread are less frequent than in carcinoma developing on cirrhosis due to other causes."} {"id": "PMID:175471", "title": "[Study of the incidence of complement-fixing antibodies against the cytomegalovirus in 339 subjects].", "content": "The authors studied complement-fixing anticytomegalovirus antibodies in a population of 339 subjects, divided up into 8 groups, from birth to 60 years. The adult group consisted of blood donors. At birth, the new-born acquired temporary passive immunity from their mothers ; then they became actively immunised over the course of several years. The increase in the number of immunised subjects was greater during infancy and adolescence, passing from 6 % to 28.1 %, than during adult age (45.1 to 52.9 %). A very important difference of 17 %) definitely separated the age groups of adolescents and young adults. 47.4 % of blood donors have complement fixing anticytomegalo-virus antibodies.", "contents": "[Study of the incidence of complement-fixing antibodies against the cytomegalovirus in 339 subjects]. The authors studied complement-fixing anticytomegalovirus antibodies in a population of 339 subjects, divided up into 8 groups, from birth to 60 years. The adult group consisted of blood donors. At birth, the new-born acquired temporary passive immunity from their mothers ; then they became actively immunised over the course of several years. The increase in the number of immunised subjects was greater during infancy and adolescence, passing from 6 % to 28.1 %, than during adult age (45.1 to 52.9 %). A very important difference of 17 %) definitely separated the age groups of adolescents and young adults. 47.4 % of blood donors have complement fixing anticytomegalo-virus antibodies."} {"id": "PMID:175472", "title": "[Prognostic value of bone and marrow lesions in primary myeloid splenomegaly].", "content": "The diagnosis of myelofibrosis depends on three fundamental criteria. Myeloid metaplasia of the liver and spleen, absence of Philadelphia chromosome and a variable degree of myelofibrosis. It is thus necessary to have available bone and marrow biopsies to make the diagnosis. The analysis of elementary lesions, together with their grouping, was at the origin of various pathological classifications, including those of Hickling and Jacquillat, Chom and Ripault. The latter, adopted by most authors, distinguishes three histological types, depending on the degree of myelofibrosis and bony sclerosis. They are usually considered as successive stages of the disease.", "contents": "[Prognostic value of bone and marrow lesions in primary myeloid splenomegaly]. The diagnosis of myelofibrosis depends on three fundamental criteria. Myeloid metaplasia of the liver and spleen, absence of Philadelphia chromosome and a variable degree of myelofibrosis. It is thus necessary to have available bone and marrow biopsies to make the diagnosis. The analysis of elementary lesions, together with their grouping, was at the origin of various pathological classifications, including those of Hickling and Jacquillat, Chom and Ripault. The latter, adopted by most authors, distinguishes three histological types, depending on the degree of myelofibrosis and bony sclerosis. They are usually considered as successive stages of the disease."} {"id": "PMID:175473", "title": "[IgD myeloma. Apropos of a case].", "content": "The authors report the case of a 72 year old man admitted to hospital for thoracic pain, who was found to have an Igd myeloma of lambda type. The diagnosis, suspected, in view of anemia, raised sedimentation rate and abnormal electrophoresis of serum proteins, was confirmed by marrow examination after sternal aspiration and by the use of a specific anti-serum during immuno-electrophoresis and on Ouchteriony medium. There were radiological lesions of diffuse, decalcifying myelomatous type. The course was characterised by : 1) a constant tendency to anemia, then preterminal thrombocytopenia, whereas the leukopenia remained moderate. 2) The secondary onset of Bence-Jones proteinuria and mild albuminuria with the aggravation of pre-existing renal failure. 3) Repeated attacks of infection and the intermittent onset of mental confusion, the etiology of which was not clear. Death occurred ten months later. No autopsy was carried out. In the light of this case, the authors review the world literature and the special characteristics of IgD myeloma.", "contents": "[IgD myeloma. Apropos of a case]. The authors report the case of a 72 year old man admitted to hospital for thoracic pain, who was found to have an Igd myeloma of lambda type. The diagnosis, suspected, in view of anemia, raised sedimentation rate and abnormal electrophoresis of serum proteins, was confirmed by marrow examination after sternal aspiration and by the use of a specific anti-serum during immuno-electrophoresis and on Ouchteriony medium. There were radiological lesions of diffuse, decalcifying myelomatous type. The course was characterised by : 1) a constant tendency to anemia, then preterminal thrombocytopenia, whereas the leukopenia remained moderate. 2) The secondary onset of Bence-Jones proteinuria and mild albuminuria with the aggravation of pre-existing renal failure. 3) Repeated attacks of infection and the intermittent onset of mental confusion, the etiology of which was not clear. Death occurred ten months later. No autopsy was carried out. In the light of this case, the authors review the world literature and the special characteristics of IgD myeloma."} {"id": "PMID:175474", "title": "[Hemorrhagic gastritis caused by localised intravascular coagulation during the course of cryptogenic inflammatory cirrhosis].", "content": "The authors report here a case of antral hemorrhagic gastritis without ulceration nor erosion, but with intravascular coagulation within the chorionic layer, which had a prolonged course in a patient with non-alcoholic cirrhosis, and which continued in spite of surgical cure of portal hypertension. The authors discuss various theories which might explain this hemorrhage and the development of localised intravascular coagulation, together with its relationship with the cirrhosis.", "contents": "[Hemorrhagic gastritis caused by localised intravascular coagulation during the course of cryptogenic inflammatory cirrhosis]. The authors report here a case of antral hemorrhagic gastritis without ulceration nor erosion, but with intravascular coagulation within the chorionic layer, which had a prolonged course in a patient with non-alcoholic cirrhosis, and which continued in spite of surgical cure of portal hypertension. The authors discuss various theories which might explain this hemorrhage and the development of localised intravascular coagulation, together with its relationship with the cirrhosis."} {"id": "PMID:175475", "title": "[Sex hormones and calcitonin secretion].", "content": "The increase in serum calcitonin during pregnoncy raises the problem of the role of oestrogens in the secretion of calcitonin. The authors show that oestrogen causes, in castrated rats, an increase in calcitonin activity as measured in the plasma by a biological method. This effect of injected oestrogen does not occur if the castrated animal is also submitted to thyroidectomy. The effects of progesterone studied on a small number of cases, seem to be less marked. This report shows that oestrogens have a synergistic effect with calcitonin in the maintenance of calcium within the bone. This is of importance during pregnancy and after the menopause.", "contents": "[Sex hormones and calcitonin secretion]. The increase in serum calcitonin during pregnoncy raises the problem of the role of oestrogens in the secretion of calcitonin. The authors show that oestrogen causes, in castrated rats, an increase in calcitonin activity as measured in the plasma by a biological method. This effect of injected oestrogen does not occur if the castrated animal is also submitted to thyroidectomy. The effects of progesterone studied on a small number of cases, seem to be less marked. This report shows that oestrogens have a synergistic effect with calcitonin in the maintenance of calcium within the bone. This is of importance during pregnancy and after the menopause."} {"id": "PMID:175476", "title": "[Our experience with the radioimmunoassay of insulin: Its practical value. Apropos of 140 cases].", "content": "What is the interest of insulin determinations in diabetics? The interest is considerable, scientifically, particularly in obese patients with hyperinsulinism. In practice, in intermediate cases of diabetes, it may help in deciding whether or not to administer insulin. The authors studied insulin secretion in various varieties of diabetes and its role in the onset of vascular complications. Low insulin secretion seems to favour the development and frequency of the latter.", "contents": "[Our experience with the radioimmunoassay of insulin: Its practical value. Apropos of 140 cases]. What is the interest of insulin determinations in diabetics? The interest is considerable, scientifically, particularly in obese patients with hyperinsulinism. In practice, in intermediate cases of diabetes, it may help in deciding whether or not to administer insulin. The authors studied insulin secretion in various varieties of diabetes and its role in the onset of vascular complications. Low insulin secretion seems to favour the development and frequency of the latter."} {"id": "PMID:175477", "title": "[Diagnosis of human active or latent human brucellosis by lymphocyte transformation. Inhibition of leukocyte migration and passive hemagglutination. Possible interference between brucellosis and some mental disorders].", "content": "Passive hemagglutination tests (H.T.), involving the coating of a soluble B. abortus antigen onto sheep red blood cells through chromium chloride, were always negative in non-brucellic subjects. Positive H.T., even at low titers (1:50), were associated with positive specific lymphoblastic (T.T.L.) and inhibition of leucocyte migration (I.M.L.) tests in 13 patients. These 3 tests were negative in 17 control brucellosis-free individuals. Positive H.T. confirmed a clinical diagnosis of brucellosis in 27 patients with dubious or negative responses to classical tests. Low positive (1:50, 1:100) H.T. may correspond to Brucella primary-infection or to a quiescent chronic infection, and higher titers to clinically active brucellosis. There is a correlation between cellular immunity tests (T.T.L., I.M.L.) and passive hemagglutination test. Furthermore, 39/88 women hospitalized in psychiatric wards were positive to H.T., and 6 of them were also highly positive to complement fixation and tube agglutination tests. Three T.T.L. and I.M.L., performed on samples from 3 H.T. (1:50) positive patients, were positive. These 30 patients were classified as depression or severe anorexia.", "contents": "[Diagnosis of human active or latent human brucellosis by lymphocyte transformation. Inhibition of leukocyte migration and passive hemagglutination. Possible interference between brucellosis and some mental disorders]. Passive hemagglutination tests (H.T.), involving the coating of a soluble B. abortus antigen onto sheep red blood cells through chromium chloride, were always negative in non-brucellic subjects. Positive H.T., even at low titers (1:50), were associated with positive specific lymphoblastic (T.T.L.) and inhibition of leucocyte migration (I.M.L.) tests in 13 patients. These 3 tests were negative in 17 control brucellosis-free individuals. Positive H.T. confirmed a clinical diagnosis of brucellosis in 27 patients with dubious or negative responses to classical tests. Low positive (1:50, 1:100) H.T. may correspond to Brucella primary-infection or to a quiescent chronic infection, and higher titers to clinically active brucellosis. There is a correlation between cellular immunity tests (T.T.L., I.M.L.) and passive hemagglutination test. Furthermore, 39/88 women hospitalized in psychiatric wards were positive to H.T., and 6 of them were also highly positive to complement fixation and tube agglutination tests. Three T.T.L. and I.M.L., performed on samples from 3 H.T. (1:50) positive patients, were positive. These 30 patients were classified as depression or severe anorexia."} {"id": "PMID:175478", "title": "[Periodic hemodialysis. Application of new theories and technics to shortening the dialysis sessions].", "content": "Many attempts are now being made to reduce the time of dialysis in chronic uremia. The method developed by Funck-Brentano, Man and Sausse, which includes the use of a highly permeable membrane and precise control of ultrafiltration, is theoretically logical. It was easily applied to 22 unselected patients, treated nine hours weekly for two to eight months. Of course, the follow-up is insufficient. The dosage of products permitting the digestive elimination of phosphorus and potassium must be revised, but the improvement in physical and psychological tolerance of treatment is such that a return to long duration dialysis can no longer be considered possible.", "contents": "[Periodic hemodialysis. Application of new theories and technics to shortening the dialysis sessions]. Many attempts are now being made to reduce the time of dialysis in chronic uremia. The method developed by Funck-Brentano, Man and Sausse, which includes the use of a highly permeable membrane and precise control of ultrafiltration, is theoretically logical. It was easily applied to 22 unselected patients, treated nine hours weekly for two to eight months. Of course, the follow-up is insufficient. The dosage of products permitting the digestive elimination of phosphorus and potassium must be revised, but the improvement in physical and psychological tolerance of treatment is such that a return to long duration dialysis can no longer be considered possible."} {"id": "PMID:175485", "title": "[Cardiovascular manifestations of pancreatitis. Apropos of 4 cases].", "content": "The authors report four cases of cardiovascular signs in pancreatitis in patients aged between 31 and 42 years. They then consider the main aspects observed. T-wave disorders, pericarditis, myocardial infarction and coronary heart disease and arterio-pancreatic syndrome. They consider the points in common between myocardial infarction and acute pancreatitis and then review the various pathogenic theories proposed.", "contents": "[Cardiovascular manifestations of pancreatitis. Apropos of 4 cases]. The authors report four cases of cardiovascular signs in pancreatitis in patients aged between 31 and 42 years. They then consider the main aspects observed. T-wave disorders, pericarditis, myocardial infarction and coronary heart disease and arterio-pancreatic syndrome. They consider the points in common between myocardial infarction and acute pancreatitis and then review the various pathogenic theories proposed."} {"id": "PMID:175481", "title": "[Posterior fossa syndrome terminating the course of histiocytosis X. Study of lesions of the central nervous system. Association with polyvinylpyrrolidone thesaurismosis].", "content": "The authors report the pathological and clinical findings in a case of histiocytosis X in a child. A rapidly progressive neurological syndrome of brain stem damage, occurred 5 years after the onset. Blockage of the 3rd ventricle led to surgical exploration of the posterior fossa. Lesions of the brain stem and cerebellum, in addition to the granuloma of the hypothalamus, are described. The neurological symptoms in histiocytosis X often suggest a space-occupying lesion but usually occur in the later prolonged forms in the adult. Association of thesaurismosis due to P.V.P., of therapeutic origin, produced numerous clinical skin and joint signs.", "contents": "[Posterior fossa syndrome terminating the course of histiocytosis X. Study of lesions of the central nervous system. Association with polyvinylpyrrolidone thesaurismosis]. The authors report the pathological and clinical findings in a case of histiocytosis X in a child. A rapidly progressive neurological syndrome of brain stem damage, occurred 5 years after the onset. Blockage of the 3rd ventricle led to surgical exploration of the posterior fossa. Lesions of the brain stem and cerebellum, in addition to the granuloma of the hypothalamus, are described. The neurological symptoms in histiocytosis X often suggest a space-occupying lesion but usually occur in the later prolonged forms in the adult. Association of thesaurismosis due to P.V.P., of therapeutic origin, produced numerous clinical skin and joint signs."} {"id": "PMID:175486", "title": "[Recurrent acute pericarditis and corticoid dependence. Apropos of 10 cases].", "content": "The authors report ten cases of acute recurrent pericarditis observed over a period of 5 years and emphasize the frequency of these relapses involving 15 to 20% of cases of acute pericarditis. Usually, no cause is found and, althrough an immunological mechanism has been suggested, there is no common test which may confirm or disprove this theory. The risk of ultimate constrictive pericarditis is minimal and this risk is thus not taken into consideration in deciding on treatment. On the other hand, the undesirable effects of corticosteroids which favour relapses, seem to be demonstrated. The use of corticosteroids in cases of acute pericarditis should thus be exceptional and one should prefer non-steroid anti-inflammatory drugs. Immunosuppressors and pericardectomy should be reserved for the rare forms where the disease progresses and relapses continue after cortisone has been stopped.", "contents": "[Recurrent acute pericarditis and corticoid dependence. Apropos of 10 cases]. The authors report ten cases of acute recurrent pericarditis observed over a period of 5 years and emphasize the frequency of these relapses involving 15 to 20% of cases of acute pericarditis. Usually, no cause is found and, althrough an immunological mechanism has been suggested, there is no common test which may confirm or disprove this theory. The risk of ultimate constrictive pericarditis is minimal and this risk is thus not taken into consideration in deciding on treatment. On the other hand, the undesirable effects of corticosteroids which favour relapses, seem to be demonstrated. The use of corticosteroids in cases of acute pericarditis should thus be exceptional and one should prefer non-steroid anti-inflammatory drugs. Immunosuppressors and pericardectomy should be reserved for the rare forms where the disease progresses and relapses continue after cortisone has been stopped."} {"id": "PMID:175482", "title": "[Pancytopenic form of acute tuberculosis].", "content": "The authors report two cases of febrile pancytopenia of tuberculous origin. In both cases specific antibiotic treatment led to disappearance of the clinical and blood signs. These cases, together with 65 others, found in the world literature were then analysed. In most cases (54), death occurred owing to lack of early diagnosis and treatment, whilst in 14 cases, cure was obtained when the treatment was not started to late. The authors emphasize the necessity of liver biopsy to make the diagnosis of tuberculosis in any case of unexplained pancytopenia with fever.", "contents": "[Pancytopenic form of acute tuberculosis]. The authors report two cases of febrile pancytopenia of tuberculous origin. In both cases specific antibiotic treatment led to disappearance of the clinical and blood signs. These cases, together with 65 others, found in the world literature were then analysed. In most cases (54), death occurred owing to lack of early diagnosis and treatment, whilst in 14 cases, cure was obtained when the treatment was not started to late. The authors emphasize the necessity of liver biopsy to make the diagnosis of tuberculosis in any case of unexplained pancytopenia with fever."} {"id": "PMID:175483", "title": "[Several methodologic aspects of chronic bronchitis surveys].", "content": "The frequency of chronic bronchitis and the late and irreversible character of the respiratory invalidity thus caused, led to recognition at an early stage when the disease is usually neglected by the patient. In the choice of examinations designed to select pathological cases, it is important to take into consideration a few elementary notions of methodology. 1 - Precise definition of objectives. 2 - Drawing up a questionnaire and evaluation of its performance. 3 - The place, execution and interpretation of morphological and functional investigations, are the main points developed from personal investigations and similar investigations carried out in other countries. Quality controls of these main methods of analysis of the disease under study are necessary for reliable numerical evaluation. The principles drawn up should be borne in mind at a time when epidemiology is occupying a basic position in bioclinical research and numerous attempts have been made to carry out investigations from which one should obtain the maximum information.", "contents": "[Several methodologic aspects of chronic bronchitis surveys]. The frequency of chronic bronchitis and the late and irreversible character of the respiratory invalidity thus caused, led to recognition at an early stage when the disease is usually neglected by the patient. In the choice of examinations designed to select pathological cases, it is important to take into consideration a few elementary notions of methodology. 1 - Precise definition of objectives. 2 - Drawing up a questionnaire and evaluation of its performance. 3 - The place, execution and interpretation of morphological and functional investigations, are the main points developed from personal investigations and similar investigations carried out in other countries. Quality controls of these main methods of analysis of the disease under study are necessary for reliable numerical evaluation. The principles drawn up should be borne in mind at a time when epidemiology is occupying a basic position in bioclinical research and numerous attempts have been made to carry out investigations from which one should obtain the maximum information."} {"id": "PMID:175487", "title": "[Thrombopenic purpura revealing Hodgkin's disease].", "content": "The authors report a case of Hodgkin's disease at the subdiaphragmatic II B b stage with cell type III, revealed by thrombopenic purpura. Laparotomy and splenectomy confirmed the invasion of the spleen whereas there was no clinical splenomegaly and splenic radio-isotope scan was normal. The course is at present favourable, the purpura has been treated by corticotherapy then splenectomy, and the disease has been brought under control by classical treatment (cobalt radiotherapy and chemotherapy). The authors then discuss eight other cases in the world literature. Splenectomy is of dual interest for the assessment of Hodgkin's disease, on the one hand, and for the treatment of thrombopenic purpura on the other hand.", "contents": "[Thrombopenic purpura revealing Hodgkin's disease]. The authors report a case of Hodgkin's disease at the subdiaphragmatic II B b stage with cell type III, revealed by thrombopenic purpura. Laparotomy and splenectomy confirmed the invasion of the spleen whereas there was no clinical splenomegaly and splenic radio-isotope scan was normal. The course is at present favourable, the purpura has been treated by corticotherapy then splenectomy, and the disease has been brought under control by classical treatment (cobalt radiotherapy and chemotherapy). The authors then discuss eight other cases in the world literature. Splenectomy is of dual interest for the assessment of Hodgkin's disease, on the one hand, and for the treatment of thrombopenic purpura on the other hand."} {"id": "PMID:175489", "title": "[Acute transformation in 45 cases of chronic myeloid leukemia].", "content": "After a chronic phase, the average duration of which in this series was 38 months, the acute phase of myeloid leukemia was very short, not exceeding 7 months. The clinical signs which suggest an acute exacerbation are, in order of importance, increase in the volume of the spleen, changes in general health, fever. The blood signs, which are often found later than the clinical signs, are increased white cell count, anemia and marrow leukoblastosis higher than 20%. The laboratory criteria of acute exacerbation are of lesser importance. Chemotherapy gives very poor results at this stage.", "contents": "[Acute transformation in 45 cases of chronic myeloid leukemia]. After a chronic phase, the average duration of which in this series was 38 months, the acute phase of myeloid leukemia was very short, not exceeding 7 months. The clinical signs which suggest an acute exacerbation are, in order of importance, increase in the volume of the spleen, changes in general health, fever. The blood signs, which are often found later than the clinical signs, are increased white cell count, anemia and marrow leukoblastosis higher than 20%. The laboratory criteria of acute exacerbation are of lesser importance. Chemotherapy gives very poor results at this stage."} {"id": "PMID:175490", "title": "[Water-electrolyte re-equilibration in chronic interstitial nephritis].", "content": "In chronic interstitial nephritis there is a salt-losing syndrome. The reduction in the number of nephrons provides an experimental model for a study of the effects of a sodium load on the kidney. Partial restoral of renal function follows administration of sodium chloride and permits one to consider the main mechanisms of the regulation of sodium balance.", "contents": "[Water-electrolyte re-equilibration in chronic interstitial nephritis]. In chronic interstitial nephritis there is a salt-losing syndrome. The reduction in the number of nephrons provides an experimental model for a study of the effects of a sodium load on the kidney. Partial restoral of renal function follows administration of sodium chloride and permits one to consider the main mechanisms of the regulation of sodium balance."} {"id": "PMID:175491", "title": "[Actinomycosis. Apropos 4 cases with thoracic and abdominal localization].", "content": "Actinomycosis is a rare disease and may be discovered at operation. It may produce numberous thoracic or abdominal signs; the diagnosis is very difficult and requires histological examination.", "contents": "[Actinomycosis. Apropos 4 cases with thoracic and abdominal localization]. Actinomycosis is a rare disease and may be discovered at operation. It may produce numberous thoracic or abdominal signs; the diagnosis is very difficult and requires histological examination."} {"id": "PMID:175493", "title": "[Association of Beh\u00e7et's disease and pelvispondylitis in a subject without HLA W 27 antigen].", "content": "The authors report a new case of Behcet's disease in association with ankylosing spondylitis. A study of the HLA system in this patient, showed the presence of an HLA 5 (Behcet's disease) and the absence of HLA W 27 (ankylosing spondylitis). The authors recall the frequency of HLA W 27 during ankylosing spondylitis, whether primary or associated with psoriasis, or enteric disease. Desensitisation to autologous saliva proved a failure. A trial of D-Penicillamine produced no beneficial effect on the course of the mucosal ulcers and the inflammatory joints.", "contents": "[Association of Beh\u00e7et's disease and pelvispondylitis in a subject without HLA W 27 antigen]. The authors report a new case of Behcet's disease in association with ankylosing spondylitis. A study of the HLA system in this patient, showed the presence of an HLA 5 (Behcet's disease) and the absence of HLA W 27 (ankylosing spondylitis). The authors recall the frequency of HLA W 27 during ankylosing spondylitis, whether primary or associated with psoriasis, or enteric disease. Desensitisation to autologous saliva proved a failure. A trial of D-Penicillamine produced no beneficial effect on the course of the mucosal ulcers and the inflammatory joints."} {"id": "PMID:175494", "title": "[Gastric and pleural localization of Waldenstr\u00f6m's disease].", "content": "The authors report a case of Waldenstrom's disease, the first sign of which, remaining for a long time the only sign, was a pseudo-carcinomatous infiltration of the stomach. Later, the patient developed a pleural localisation. These two lesions, gastric and pleural, are known but rare. The authors recall the main signs. They emphasize the long duration of the disease when treated by chlorambucil. A pathological IgM was found, not only in the serum of this patient, but also in the jejunal fluid aspirated during small intestinal biopsy.", "contents": "[Gastric and pleural localization of Waldenstr\u00f6m's disease]. The authors report a case of Waldenstrom's disease, the first sign of which, remaining for a long time the only sign, was a pseudo-carcinomatous infiltration of the stomach. Later, the patient developed a pleural localisation. These two lesions, gastric and pleural, are known but rare. The authors recall the main signs. They emphasize the long duration of the disease when treated by chlorambucil. A pathological IgM was found, not only in the serum of this patient, but also in the jejunal fluid aspirated during small intestinal biopsy."} {"id": "PMID:175495", "title": "[Isolated rupture of the chordae tendineae of the mitral valve].", "content": "The authors report a personal case of mitral incompetence, due to rupture of the chordae tendineae and note the signs of this disease. The patient first developed pulmonary oedema with thoracic pain, a mitral systolic murmur and a presystolic gallop rhythm, which suggested the diagnosis in a patient in sinus rhythm with a normal size heart, the left atrium was expansive and there were obvious signs of pulmonary congestion. The rapidly fatal course may be explained by the large number of ruptured chordae tendineae. Autopsy showed that the mitral valve was normal in texture. Histological study of the ruptured cord, showed lesions of dense hyaline fibrosis and mucoid infiltration of the basic substance.", "contents": "[Isolated rupture of the chordae tendineae of the mitral valve]. The authors report a personal case of mitral incompetence, due to rupture of the chordae tendineae and note the signs of this disease. The patient first developed pulmonary oedema with thoracic pain, a mitral systolic murmur and a presystolic gallop rhythm, which suggested the diagnosis in a patient in sinus rhythm with a normal size heart, the left atrium was expansive and there were obvious signs of pulmonary congestion. The rapidly fatal course may be explained by the large number of ruptured chordae tendineae. Autopsy showed that the mitral valve was normal in texture. Histological study of the ruptured cord, showed lesions of dense hyaline fibrosis and mucoid infiltration of the basic substance."} {"id": "PMID:175496", "title": "[Brown-Sequard syndrome and extradural spinal cord hematoma in a patient taking antivitamin K].", "content": "The authors report a new case of extra-dural hematoma of the spinal cord due to anticoagulants causing a clinical Brown-Sequard syndrome. Spontaneous recovery, which was almost complete, appears quite exceptional.", "contents": "[Brown-Sequard syndrome and extradural spinal cord hematoma in a patient taking antivitamin K]. The authors report a new case of extra-dural hematoma of the spinal cord due to anticoagulants causing a clinical Brown-Sequard syndrome. Spontaneous recovery, which was almost complete, appears quite exceptional."} {"id": "PMID:175497", "title": "[Acute obstruction of the esophagus by mucilage].", "content": "The authors present the case of an 84 year-old woman with chronic constipation who suddenly developed acute obstruction of the lower oesophagus on taking a tablespoonful of mucilage without water. The obstruction was relieved by fiber endoscopy. There was no other previous lesion which might explain this complication. The patient was seen again later in good general health. The authors recall the clinical and radiological signs of acute obstruction of the oesophagus and discuss the physiopathology. They propose treating them exclusively by oesophageal fiber endoscopy.", "contents": "[Acute obstruction of the esophagus by mucilage]. The authors present the case of an 84 year-old woman with chronic constipation who suddenly developed acute obstruction of the lower oesophagus on taking a tablespoonful of mucilage without water. The obstruction was relieved by fiber endoscopy. There was no other previous lesion which might explain this complication. The patient was seen again later in good general health. The authors recall the clinical and radiological signs of acute obstruction of the oesophagus and discuss the physiopathology. They propose treating them exclusively by oesophageal fiber endoscopy."} {"id": "PMID:175498", "title": "[Basal cell epithelioma and multiple fibroepithelial Pinkus' tumors in the lumbosacral region. Discussion of the precipitating role of previous radiotherapy treatment. Apropos of 4 cases].", "content": "The authors report 4 cases of multiple tumors of the lumbo-sacral region with, on histology, a mixture of basal cell carcinomas and fibro-epithelial Pinkus tumours. They were struck by the fact that three of these four patients had received, in this region, radiotherapy numerous years previously. They discuss the role of this radiotherapy in the onset of the disease and the relative importance of this factor and of constitutional factors (Hamartomas). They recall the characteristics of multiple basal cell carcinomas and of Pinkus fibro-epithelial tumours, together with the close relationship between these two types of tumour.", "contents": "[Basal cell epithelioma and multiple fibroepithelial Pinkus' tumors in the lumbosacral region. Discussion of the precipitating role of previous radiotherapy treatment. Apropos of 4 cases]. The authors report 4 cases of multiple tumors of the lumbo-sacral region with, on histology, a mixture of basal cell carcinomas and fibro-epithelial Pinkus tumours. They were struck by the fact that three of these four patients had received, in this region, radiotherapy numerous years previously. They discuss the role of this radiotherapy in the onset of the disease and the relative importance of this factor and of constitutional factors (Hamartomas). They recall the characteristics of multiple basal cell carcinomas and of Pinkus fibro-epithelial tumours, together with the close relationship between these two types of tumour."} {"id": "PMID:175499", "title": "[Bone marrow biopsy in the diagnosis of hematopoietic tuberculosis].", "content": "The authors report 6 cases of tuberculosis of the bone marrow, in which the diagnosis was made by biopsy. Three of these cases, included peripheral blood abnormalities, such as pancytopenia, whereas in the three other, nothing special was found on routine blood examination. All the patients, except one who died from intercurrent infection, became cured thanks to anti-tuberculosis treatment. Marrow biopsy thus permits early diagnosis, miliary tuberculosis, even when usual radiological and bacteriological investigations are negative.", "contents": "[Bone marrow biopsy in the diagnosis of hematopoietic tuberculosis]. The authors report 6 cases of tuberculosis of the bone marrow, in which the diagnosis was made by biopsy. Three of these cases, included peripheral blood abnormalities, such as pancytopenia, whereas in the three other, nothing special was found on routine blood examination. All the patients, except one who died from intercurrent infection, became cured thanks to anti-tuberculosis treatment. Marrow biopsy thus permits early diagnosis, miliary tuberculosis, even when usual radiological and bacteriological investigations are negative."} {"id": "PMID:175500", "title": "[Primary malignant tumor of the liver in children].", "content": "Primary malignant tumours of the liver in children are rare. They occur in more than 50% of cases before the age of 2 years. The clinical signs are very often limited to a large mass in the right hypochrondrium. A search for alphafoetoprotein and arteriography are the most useful investigations for diagnosis. The pathology leads one to distinguish hepatoblastomas and hepatocarcinomas. The prognosis in these tumours remains poor for, in spite of progress in liver surgery, a cure is rarely possible. It is important for doctors to recognize the existence of this tumour pathology in order to give a chance for surgery to succeed in these young children. To illustrate this, 5 cases from Besan\u00e7on are reported here.", "contents": "[Primary malignant tumor of the liver in children]. Primary malignant tumours of the liver in children are rare. They occur in more than 50% of cases before the age of 2 years. The clinical signs are very often limited to a large mass in the right hypochrondrium. A search for alphafoetoprotein and arteriography are the most useful investigations for diagnosis. The pathology leads one to distinguish hepatoblastomas and hepatocarcinomas. The prognosis in these tumours remains poor for, in spite of progress in liver surgery, a cure is rarely possible. It is important for doctors to recognize the existence of this tumour pathology in order to give a chance for surgery to succeed in these young children. To illustrate this, 5 cases from Besan\u00e7on are reported here."} {"id": "PMID:175503", "title": "[Waldenstr\u00f4m's macroglobulinemia. Developmental and prognostic study].", "content": "The course of 27 cases of Waldenstr\u00f6m's macroglobuilinemia was observed during at least 2 years or until death. A worsening occurred in half of the patients, with 7 deaths before 2 years. 10 patients improved under therapy, with only two deaths later. The more frequent complications were infections, but other complications, haemorragic, neurologic, osseous and renal were also observed. A haemoglobin initial level higher than 9 g % and a significant decrease of lymphocyte blood count under chemotherapy seem to be of good prognosis.", "contents": "[Waldenstr\u00f4m's macroglobulinemia. Developmental and prognostic study]. The course of 27 cases of Waldenstr\u00f6m's macroglobuilinemia was observed during at least 2 years or until death. A worsening occurred in half of the patients, with 7 deaths before 2 years. 10 patients improved under therapy, with only two deaths later. The more frequent complications were infections, but other complications, haemorragic, neurologic, osseous and renal were also observed. A haemoglobin initial level higher than 9 g % and a significant decrease of lymphocyte blood count under chemotherapy seem to be of good prognosis."} {"id": "PMID:175504", "title": "[Morphologic manifestations of Waldenstr\u00f6m's disease].", "content": "The authors describe the various cytological and pathological lesions found in lymph node, spleen, bone marrow and liver in Waldenstr\u00f6ms macroglobulinemia. The significance of the discovery of PAS positive intranuclear vacuoles is discussed. The findings are completed by a description of the results obtained in immunofluorescence and under the electron microscope. Unusual forms and the differential pathological diagnosis are then discussed.", "contents": "[Morphologic manifestations of Waldenstr\u00f6m's disease]. The authors describe the various cytological and pathological lesions found in lymph node, spleen, bone marrow and liver in Waldenstr\u00f6ms macroglobulinemia. The significance of the discovery of PAS positive intranuclear vacuoles is discussed. The findings are completed by a description of the results obtained in immunofluorescence and under the electron microscope. Unusual forms and the differential pathological diagnosis are then discussed."} {"id": "PMID:175505", "title": "[Sarcomatous and leukemic forms of Waldenstr\u00f6m's macroglobulinemia].", "content": "Four cases of sarcomatous or leukaemic types of Waldenstr\u00f6m's macroglobulinemia are presented. They are characterized by tumoral and compressive localizations of lymph node or spleen, or by a hyper-leukocytosis with many circulating abnormal cells. These cells are different from the lympho-plasma cells regularly observed in Waldenstr\u00f6m's macroglobulinemia, and can be assimilated to malignant immunoblasts. They have a proliferative aspect and seem to produce less macroglobulin and to recover some beta-glucuronidase activity. The sarcomatous and leukemic types of Waldenstr\u00f6m's macroglobullinemia have a poor prognosis and may appear as terminal transformation of the disease.", "contents": "[Sarcomatous and leukemic forms of Waldenstr\u00f6m's macroglobulinemia]. Four cases of sarcomatous or leukaemic types of Waldenstr\u00f6m's macroglobulinemia are presented. They are characterized by tumoral and compressive localizations of lymph node or spleen, or by a hyper-leukocytosis with many circulating abnormal cells. These cells are different from the lympho-plasma cells regularly observed in Waldenstr\u00f6m's macroglobulinemia, and can be assimilated to malignant immunoblasts. They have a proliferative aspect and seem to produce less macroglobulin and to recover some beta-glucuronidase activity. The sarcomatous and leukemic types of Waldenstr\u00f6m's macroglobullinemia have a poor prognosis and may appear as terminal transformation of the disease."} {"id": "PMID:175506", "title": "[Waldenstr\u00f6m's macroglobulinemia with preserved antierythrocyte and antilipoprotein antibody activity].", "content": "One case of Waldenstr\u00f6m's macroglobulinemia is reported, in which the monoclonal IgM has an antibody activity against stored red cells, beta-lipoproteins and mammalian glomeruli. The antibody activity is observed with the purified IgM molecule, which cross reacts with the three antigens, and with the Fab piece. The study of the cross reactions shows that the antibody recognizes similar rather than identical antigens. This observation is to be added to the few cases already published of antibody against stored red cells, and of Waldenstr\u00f6m's macroglobulinemia with antibody activity. The physiopathology of the occurrence of a M component with such an activity is discussed.", "contents": "[Waldenstr\u00f6m's macroglobulinemia with preserved antierythrocyte and antilipoprotein antibody activity]. One case of Waldenstr\u00f6m's macroglobulinemia is reported, in which the monoclonal IgM has an antibody activity against stored red cells, beta-lipoproteins and mammalian glomeruli. The antibody activity is observed with the purified IgM molecule, which cross reacts with the three antigens, and with the Fab piece. The study of the cross reactions shows that the antibody recognizes similar rather than identical antigens. This observation is to be added to the few cases already published of antibody against stored red cells, and of Waldenstr\u00f6m's macroglobulinemia with antibody activity. The physiopathology of the occurrence of a M component with such an activity is discussed."} {"id": "PMID:175508", "title": "Pancytopenia and \"caillary leak syndrome\" with infectious mononucleosis.", "content": "A 19-year-old man with documented infectious mononucleosis presented with pancytopenia and a megaloblastic bone marrow. He developed a \"capillary leak syndrome\" with an expanded plasma volume of 9,290 ml and normal right heart and pulmonary artery pressures. The patient had a dramatic recovery after corticosteroid therapy.", "contents": "Pancytopenia and \"caillary leak syndrome\" with infectious mononucleosis. A 19-year-old man with documented infectious mononucleosis presented with pancytopenia and a megaloblastic bone marrow. He developed a \"capillary leak syndrome\" with an expanded plasma volume of 9,290 ml and normal right heart and pulmonary artery pressures. The patient had a dramatic recovery after corticosteroid therapy."} {"id": "PMID:175510", "title": "Meigs' syndrome. A case report.", "content": "A case of Meig's syndrome is reported and the rarity of this condition is emphasised. The need for exploratory laparotomy in patients with solid ovarian tumours associated with ascites and pleural effusion, and free of malignant cells, is stressed.", "contents": "Meigs' syndrome. A case report. A case of Meig's syndrome is reported and the rarity of this condition is emphasised. The need for exploratory laparotomy in patients with solid ovarian tumours associated with ascites and pleural effusion, and free of malignant cells, is stressed."} {"id": "PMID:175523", "title": "[Transmissible Gastroenteritis in Swine (author's transl)].", "content": "Transmissible gastroenteritis or TGE is a virus diarrhoea which occurs in pigs of all ages and is associated with high mortality rates in the young piglets. Growth of virus in the columnar epithelium of the small intestine causes atrophy of the intestinal villi, malabsorption, watery diarrhoea and dehydration. Faecal excretion of virus usually continues up to fourteen days after infection but chronic carriers have been found to occur. TGE is self-limiting on the majority of pig-breeding farms but the virus may persist in particular conditions and an enzootic form of the disease will appear in this case. In typical outbreaks, the diagnosis can usually be based on clinical symptoms. When the disease runs an enzootic course, a clinical diagnosis will be out of the question. TGE should be differentiated from colibacillosis and from another virus diarrhoea, the aetiology of which is not precisely known. A rapid and correct diagnosis may be established by direct fluorescent antibody studies of frozen sections of the small intestine in infected piglets. When sows have been spontaneously infected, their offspring will be protected by lactogenic immunity. The presence of TGE antibodies of IgA class in the milk is required to ensure complete immunity of the piglets lasting for weeks on end. Intramuscular inoculation of a commercially available vaccine in sows will only stimulate the production of antibodies of the IgG class in the milk. These antibodies will merely afford short-lived immunity. The vaccine cannot prevent symptoms of disease from appearing in piglets following infection with virulent TGE virus but it does reduce mortality", "contents": "[Transmissible Gastroenteritis in Swine (author's transl)]. Transmissible gastroenteritis or TGE is a virus diarrhoea which occurs in pigs of all ages and is associated with high mortality rates in the young piglets. Growth of virus in the columnar epithelium of the small intestine causes atrophy of the intestinal villi, malabsorption, watery diarrhoea and dehydration. Faecal excretion of virus usually continues up to fourteen days after infection but chronic carriers have been found to occur. TGE is self-limiting on the majority of pig-breeding farms but the virus may persist in particular conditions and an enzootic form of the disease will appear in this case. In typical outbreaks, the diagnosis can usually be based on clinical symptoms. When the disease runs an enzootic course, a clinical diagnosis will be out of the question. TGE should be differentiated from colibacillosis and from another virus diarrhoea, the aetiology of which is not precisely known. A rapid and correct diagnosis may be established by direct fluorescent antibody studies of frozen sections of the small intestine in infected piglets. When sows have been spontaneously infected, their offspring will be protected by lactogenic immunity. The presence of TGE antibodies of IgA class in the milk is required to ensure complete immunity of the piglets lasting for weeks on end. Intramuscular inoculation of a commercially available vaccine in sows will only stimulate the production of antibodies of the IgG class in the milk. These antibodies will merely afford short-lived immunity. The vaccine cannot prevent symptoms of disease from appearing in piglets following infection with virulent TGE virus but it does reduce mortality"} {"id": "PMID:175525", "title": "Progesterone in the uterus. V. Correlation of the in vitro progesterone metabolism with the progesterone binding in rat uterus.", "content": "Incubations of rat uterine segments with varying 3H-progesterone concentrations were performed to study the hormone uptake by the tissue. The radioactivity of the uterus and the nutrient medium were plotted in form of a SCATCHARD plot. Additionally, the binding capacity of the uterine cytosol was measured. In both systems, the hormone was found to be associated with two components which differ from each other in their association constants. The progesterone metabolism occuring at a hormone concentration of 10(-6)M and more in the incubation medium is discussed with respect to the affinity and the capacity of the hormone binding components.", "contents": "Progesterone in the uterus. V. Correlation of the in vitro progesterone metabolism with the progesterone binding in rat uterus. Incubations of rat uterine segments with varying 3H-progesterone concentrations were performed to study the hormone uptake by the tissue. The radioactivity of the uterus and the nutrient medium were plotted in form of a SCATCHARD plot. Additionally, the binding capacity of the uterine cytosol was measured. In both systems, the hormone was found to be associated with two components which differ from each other in their association constants. The progesterone metabolism occuring at a hormone concentration of 10(-6)M and more in the incubation medium is discussed with respect to the affinity and the capacity of the hormone binding components."} {"id": "PMID:175526", "title": "Dynamics of estrone glucosiduronate metabolism in dogs.", "content": "Interest in the metabolism of estrogen conjugates has been increased by the recent demonstration that some of these conjugates can be hydrolysed in vivo, and are thus a source of physiologically-active circulating estrogens. In this report the metabolism of the quantitatively important conjugate estrone glucosiduronate has been studied in dogs, following the intravenous infusion of 3H-estrone glucosiduronate. Arterial plasma levels of radioactive estrone glucosiduronate and of the radioactive metabolites estrone, estradiol-17beta-3-glucosiduronate and estradiol-17alpha-3-glucosiduronate were measured. The metabolic clearance rate of estrone glucosiduronate (MCREG) was determined, as well as conversion ratios for estrone glucosiduronate to estrone (CREG.E), estradiol-17beta-3-glucosiduronate (CREG.E2betaG) and estradiol-17alpha-3-glucosiduronate (CREG.E2alphaG). Sequential values for the above mentioned conversion ratios were obtained and the relationship to time was analysed. Transfer constants for estrone glucosiduronate to estrone (rhoEG.E) were measured. The mean MCREG was 329 L/day/m2, SE 35. The values for CREG.E2betaG and CREG.E2alphaG did not become constant until 80 minutes following the start of infusion. The mean values at a steady state were: CREG.E.021, SE .002, CREG.E2betaG .068, SE .005, CREG.E2alphaG .022, SE .002. The mean value for rhoEG.E was .057, SE .006.", "contents": "Dynamics of estrone glucosiduronate metabolism in dogs. Interest in the metabolism of estrogen conjugates has been increased by the recent demonstration that some of these conjugates can be hydrolysed in vivo, and are thus a source of physiologically-active circulating estrogens. In this report the metabolism of the quantitatively important conjugate estrone glucosiduronate has been studied in dogs, following the intravenous infusion of 3H-estrone glucosiduronate. Arterial plasma levels of radioactive estrone glucosiduronate and of the radioactive metabolites estrone, estradiol-17beta-3-glucosiduronate and estradiol-17alpha-3-glucosiduronate were measured. The metabolic clearance rate of estrone glucosiduronate (MCREG) was determined, as well as conversion ratios for estrone glucosiduronate to estrone (CREG.E), estradiol-17beta-3-glucosiduronate (CREG.E2betaG) and estradiol-17alpha-3-glucosiduronate (CREG.E2alphaG). Sequential values for the above mentioned conversion ratios were obtained and the relationship to time was analysed. Transfer constants for estrone glucosiduronate to estrone (rhoEG.E) were measured. The mean MCREG was 329 L/day/m2, SE 35. The values for CREG.E2betaG and CREG.E2alphaG did not become constant until 80 minutes following the start of infusion. The mean values at a steady state were: CREG.E.021, SE .002, CREG.E2betaG .068, SE .005, CREG.E2alphaG .022, SE .002. The mean value for rhoEG.E was .057, SE .006."} {"id": "PMID:175527", "title": "MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors.", "content": "We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones.", "contents": "MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones."} {"id": "PMID:175528", "title": "Investigations on the level of circulating eosinophils throughout a 24 hour period in parasitic disease.", "content": "Circulating absolute eosinophil levels were studied over a 24 hour period in a series of 10 patients with presumed parasitological disease. Seven of these ten had the distinct nocturnal increase and a percentage swing paralleling that found in normal subjects. Three patients had a reversed pattern. The latter were thought to have one or other form of filariasis. Two patients with loasis and a \"physiological response\" had suppression as anticipated to exogenous steroid. It is concluded that steroid administration will not separate parasitic from other causes of eosinophilia.", "contents": "Investigations on the level of circulating eosinophils throughout a 24 hour period in parasitic disease. Circulating absolute eosinophil levels were studied over a 24 hour period in a series of 10 patients with presumed parasitological disease. Seven of these ten had the distinct nocturnal increase and a percentage swing paralleling that found in normal subjects. Three patients had a reversed pattern. The latter were thought to have one or other form of filariasis. Two patients with loasis and a \"physiological response\" had suppression as anticipated to exogenous steroid. It is concluded that steroid administration will not separate parasitic from other causes of eosinophilia."} {"id": "PMID:175532", "title": "[Incorporation of radiolabel in vitro into proteins of rat hippocampus synaptosomes when elaborating defensive conditioned reflexes].", "content": "The influence of learning local protein synthesis was studied in the rat hippocampal synaptosomes. It is found that elaboration of two-way avoidance conditioned reflex causes a decrease in ability of hippocampal synaptosomes to include H3-leucin into proteins in experiments in vitro. It is suggested that cyclic adenosin 3'5'-monophosphate plays a definite role in controlling protein synthesis in the nerve endings during different influences including learning because its addition to the incubation medium activates sharply this process.", "contents": "[Incorporation of radiolabel in vitro into proteins of rat hippocampus synaptosomes when elaborating defensive conditioned reflexes]. The influence of learning local protein synthesis was studied in the rat hippocampal synaptosomes. It is found that elaboration of two-way avoidance conditioned reflex causes a decrease in ability of hippocampal synaptosomes to include H3-leucin into proteins in experiments in vitro. It is suggested that cyclic adenosin 3'5'-monophosphate plays a definite role in controlling protein synthesis in the nerve endings during different influences including learning because its addition to the incubation medium activates sharply this process."} {"id": "PMID:175533", "title": "[Peptide-hydrolase activity in different areas of brain with introduction of hydrocortisone and ACTH].", "content": "A single introduction of hydrocortisone is established to evoke an increase in the total activity of acid peptide-hydrolase in most areas of the brain. A single administration of ACTH single and long term administration of hydrocortisone was found to increase the specific activity of acid peptide-hydrolase of the soluble fraction. The specific activity of neutral peptide-hydrolase of the soluble fraction increases with a single administration of ACTH and long term administration of hydrocortisone. A single and long term administration of hydrocortisone and ACTH cause an increase in the percentage of the soluble form of peptide-hydrolases of the total activity.", "contents": "[Peptide-hydrolase activity in different areas of brain with introduction of hydrocortisone and ACTH]. A single introduction of hydrocortisone is established to evoke an increase in the total activity of acid peptide-hydrolase in most areas of the brain. A single administration of ACTH single and long term administration of hydrocortisone was found to increase the specific activity of acid peptide-hydrolase of the soluble fraction. The specific activity of neutral peptide-hydrolase of the soluble fraction increases with a single administration of ACTH and long term administration of hydrocortisone. A single and long term administration of hydrocortisone and ACTH cause an increase in the percentage of the soluble form of peptide-hydrolases of the total activity."} {"id": "PMID:175534", "title": "[Procedure for extracting polyphosphoinositides from rat liver tissue and peculiarities of their metabolism].", "content": "The content of the rat liver triphosphoinositides and diphosphoinositides was determined in fresh tissue by the extraction with acid chloroform methanol mixture. The content was 7.7 +/- 0.5 mug P and 6.4 +/- 0.5 mug per 1 g of the tissue for triphosphoinositide and diphosphoinositides, respectively. The rapid enzymatic posthumorus changes are shown for the phospholipid content in the liver tissue; 5 min after the amount of triphosphoinositides increased by 19%, diphosphoinositides -- by 13% and that of total phospholipids -- by 11%; subsequently after 30 min after the content of di- and triphosphoinositides decreases below the initial values and that of other phospholipids returns to the initial level. The rate of 32P incorporation into polyphosphoinositide fractions increases rapidly during 1 hour and considerably exceeds that of all other phospholipid fractions studied.", "contents": "[Procedure for extracting polyphosphoinositides from rat liver tissue and peculiarities of their metabolism]. The content of the rat liver triphosphoinositides and diphosphoinositides was determined in fresh tissue by the extraction with acid chloroform methanol mixture. The content was 7.7 +/- 0.5 mug P and 6.4 +/- 0.5 mug per 1 g of the tissue for triphosphoinositide and diphosphoinositides, respectively. The rapid enzymatic posthumorus changes are shown for the phospholipid content in the liver tissue; 5 min after the amount of triphosphoinositides increased by 19%, diphosphoinositides -- by 13% and that of total phospholipids -- by 11%; subsequently after 30 min after the content of di- and triphosphoinositides decreases below the initial values and that of other phospholipids returns to the initial level. The rate of 32P incorporation into polyphosphoinositide fractions increases rapidly during 1 hour and considerably exceeds that of all other phospholipid fractions studied."} {"id": "PMID:175554", "title": "[Localization of viral antigen in cell cultures infected with the IBR-IPV virus].", "content": "Using the immunofluorescence method and fluorescein-isothiocyanate-labelled antibodies against the IBR-IPV virus the dynamics was followed up of the production of the viral antigen in primary cell cultures of calf kidney and a permanent cell line of calf kidney infected with IBR-IPV strains isolated in this country. To avoid nonspecific reactions in the fluorescence-and-serologic demonstration of the viral antigen a method was employed for the contrast staining with Evans blue. A positive reaction consisting in the specific fluorescence of the membrane enveloping the nucleus appeared at the earliest four hours after the infection of the cell cultures. No differences were found between the studied IBR-IPV virus strains so far as the place and time of appearance and the development of the viral antigen in the infected cell were concerned with the use of the two types of cell cultures.", "contents": "[Localization of viral antigen in cell cultures infected with the IBR-IPV virus]. Using the immunofluorescence method and fluorescein-isothiocyanate-labelled antibodies against the IBR-IPV virus the dynamics was followed up of the production of the viral antigen in primary cell cultures of calf kidney and a permanent cell line of calf kidney infected with IBR-IPV strains isolated in this country. To avoid nonspecific reactions in the fluorescence-and-serologic demonstration of the viral antigen a method was employed for the contrast staining with Evans blue. A positive reaction consisting in the specific fluorescence of the membrane enveloping the nucleus appeared at the earliest four hours after the infection of the cell cultures. No differences were found between the studied IBR-IPV virus strains so far as the place and time of appearance and the development of the viral antigen in the infected cell were concerned with the use of the two types of cell cultures."} {"id": "PMID:175555", "title": "[Some properties of strains of the transmissible gastroenteritis virus of swine (TGE) isolated in Bulgaria].", "content": "Strains of the swine transmissive gastroenteritis (TGE) virus were isolated for the first time in Bulgaria in 1972. The dynamics was followed up of some strains' propagation in primary cell cultures of kidney tissue and subcultures of the thyroid of pigs. The intracellular virus reached highest titers at the 24--48th hour in the kidney cells, and at the 24--36th hour in the thyroid cells, while the extracellular virus was subjected to inactivation by the 2nd hour after infecting the cultures, by the 4--6th h its titer dropped up to 50 per cent of its initial value, and by the 24th h it was completely inactivated. The viability of the virus was tested after freeze-drying and after it had been stored at 4degreesC and--20degreesC. It was found that chloroform fully inactivates the virus at 4degreesC for 24 hours. The same results were obtained with the use of sodium desoxycholate. The strains isolated in this country form plaques, and with some strains the plaques are of a varying size. Halogenic desoxyuridines (IUDR, BUDR), as well as 8-azoridine do not suppress the multiplication of the tested TGE strains even in high concentrations. Inhibitory effect has 5-bromurazyl which in given concentrations affects the titer of the virus and the size of the plaques formed. Two Bulgarian and two reference strains have lowered their plaque-forming titer by 2 log after being treated with rifamycin-B or rifampicin.", "contents": "[Some properties of strains of the transmissible gastroenteritis virus of swine (TGE) isolated in Bulgaria]. Strains of the swine transmissive gastroenteritis (TGE) virus were isolated for the first time in Bulgaria in 1972. The dynamics was followed up of some strains' propagation in primary cell cultures of kidney tissue and subcultures of the thyroid of pigs. The intracellular virus reached highest titers at the 24--48th hour in the kidney cells, and at the 24--36th hour in the thyroid cells, while the extracellular virus was subjected to inactivation by the 2nd hour after infecting the cultures, by the 4--6th h its titer dropped up to 50 per cent of its initial value, and by the 24th h it was completely inactivated. The viability of the virus was tested after freeze-drying and after it had been stored at 4degreesC and--20degreesC. It was found that chloroform fully inactivates the virus at 4degreesC for 24 hours. The same results were obtained with the use of sodium desoxycholate. The strains isolated in this country form plaques, and with some strains the plaques are of a varying size. Halogenic desoxyuridines (IUDR, BUDR), as well as 8-azoridine do not suppress the multiplication of the tested TGE strains even in high concentrations. Inhibitory effect has 5-bromurazyl which in given concentrations affects the titer of the virus and the size of the plaques formed. Two Bulgarian and two reference strains have lowered their plaque-forming titer by 2 log after being treated with rifamycin-B or rifampicin."} {"id": "PMID:175556", "title": "Formaldehyde-ozone-induced fluorescence and ACTH immunoreactivity in basophil tumours of the pituitary.", "content": "The ACTH cells of human foetal pituitary displayed intense formaldehyde-ozone-induced fluorescence characteristic of peptides or proteins with NH2-terminal tryptophan. Fourteen pituitary tumours were examined histochemically. Of these, two displayed formaldehyde-ozone-induced fluorescence. These two tumours were the only ones to exhibit ACTH immunoreactivity.", "contents": "Formaldehyde-ozone-induced fluorescence and ACTH immunoreactivity in basophil tumours of the pituitary. The ACTH cells of human foetal pituitary displayed intense formaldehyde-ozone-induced fluorescence characteristic of peptides or proteins with NH2-terminal tryptophan. Fourteen pituitary tumours were examined histochemically. Of these, two displayed formaldehyde-ozone-induced fluorescence. These two tumours were the only ones to exhibit ACTH immunoreactivity."} {"id": "PMID:175557", "title": "[Alpha-1-antitrypsin deficiency in children: liver ultrastructure and speculations (author's transl)].", "content": "Fourteen liver biopsies from twelve young patients with liver diseases associated with homozygous, PiZZ phenotype, alpha-1-antitrypsin deficiency in their sera were examined by electron microscopy. In all these biopsies characteristic homogeneous material was found in some hepatocytes and corresponded, when observed on adjacent semithin sections by light microscopy, to the deposit stained by periodic acid Schiff reaction. The accumulation in perinuclear spaces resulted in intranuclear invaginations, but the major deposit was located in lumens of the endoplasmic reticulum. The limiting membranes were rough and smooth but the extent of the latter was so large that only this type of reticulum seemed peculiarly involved in the accumulating process. On the contrary, Golgi complexes did not seen obligatorily involved by this process because, when observed, they appeared almost normal even in heavily overloaded liver cells. At least for the PiZZ phenotype, the abnormal substance would be an asialo form of normal alpha-1-antitrypsin. Thus the subject of this study is the morphologic translation of an impairment in the synthesis of a glycoprotein. In the light of data concerning the synthesis of such proteins our findings lead us to suggest: The ultrastructural patterns observed in alpha-1-antitrypsin deficiency cannot give the expected morphologic evidence of the biochemical data which locate the first binding steps of monosaccharide residues in the rough endoplasmic reticulum. The absence of sialic acid could not result from an enzymatic defect primarily located in Golgi complexes but could be secondary to an impairment in the binding of one monosaccharide residue which improves subsequent fixation of sialic acid, in the smooth endoplasmic reticulum. Finally it seems necessary to emphasize that the relationship between the abnormal substance and various important non specific lesions is largely unknown and that we don't know the significance of polymorphous dense bodies observed in ductular cells during the cholestatic period.", "contents": "[Alpha-1-antitrypsin deficiency in children: liver ultrastructure and speculations (author's transl)]. Fourteen liver biopsies from twelve young patients with liver diseases associated with homozygous, PiZZ phenotype, alpha-1-antitrypsin deficiency in their sera were examined by electron microscopy. In all these biopsies characteristic homogeneous material was found in some hepatocytes and corresponded, when observed on adjacent semithin sections by light microscopy, to the deposit stained by periodic acid Schiff reaction. The accumulation in perinuclear spaces resulted in intranuclear invaginations, but the major deposit was located in lumens of the endoplasmic reticulum. The limiting membranes were rough and smooth but the extent of the latter was so large that only this type of reticulum seemed peculiarly involved in the accumulating process. On the contrary, Golgi complexes did not seen obligatorily involved by this process because, when observed, they appeared almost normal even in heavily overloaded liver cells. At least for the PiZZ phenotype, the abnormal substance would be an asialo form of normal alpha-1-antitrypsin. Thus the subject of this study is the morphologic translation of an impairment in the synthesis of a glycoprotein. In the light of data concerning the synthesis of such proteins our findings lead us to suggest: The ultrastructural patterns observed in alpha-1-antitrypsin deficiency cannot give the expected morphologic evidence of the biochemical data which locate the first binding steps of monosaccharide residues in the rough endoplasmic reticulum. The absence of sialic acid could not result from an enzymatic defect primarily located in Golgi complexes but could be secondary to an impairment in the binding of one monosaccharide residue which improves subsequent fixation of sialic acid, in the smooth endoplasmic reticulum. Finally it seems necessary to emphasize that the relationship between the abnormal substance and various important non specific lesions is largely unknown and that we don't know the significance of polymorphous dense bodies observed in ductular cells during the cholestatic period."} {"id": "PMID:175558", "title": "[Comparative light and electron microscopic studies of oncocytic pituitary adenomas (author's transl)].", "content": "In a collection of 108 surgically removed, light and electron microscopically studied pituitary tumors, 19 adenomas (17.6%) could be found of which oncocytic tumor cells constituted more than 50%. These showed histologically, in conformity with the criteria of oncocytes, a fairly broad cytoplasm with finely granular or, in part, finely vacuolar structures and distinct cell membranes. The nuclei were predominantly round and moderately rich in chromatin but also in part, pyknotic. In paraffin-embedded sections the tumors could not be distinguished with certainty from chromophobe or moderately granulated acidophil adenomas. In plastic-embedded sections they could be identified by the typical filmy and finely granular feature of the cytoplasm which was distinctly different from conglomerations of secretory granules. Ultrastructurally they were characterized by many densely packed mitochondria. These were, in part, hydropically swollen. Furthermore, 5 tumors exhibited increased hormone-synthesizing organelles, 2 of which induced an acromegaly. Probably the oncocytic pituitary adenomas are secondarily transformed chromophobe or moderately chromophil tumors which must be regarded as independent, for the most part endocrinologically inactive pituitary tumors. In addition to these purely or almost purely oncocytic tumors further 12 adenomas (11.1%) with oncocytic parts constituting between 10 and 50% of the tissue were in our collection. Of these, 5 were moderately or distinctly acidophil adenomas with clinical symptoms of acromegaly; 2 were, for the most part, mucoid cell adenomas with Nelson's syndrome.", "contents": "[Comparative light and electron microscopic studies of oncocytic pituitary adenomas (author's transl)]. In a collection of 108 surgically removed, light and electron microscopically studied pituitary tumors, 19 adenomas (17.6%) could be found of which oncocytic tumor cells constituted more than 50%. These showed histologically, in conformity with the criteria of oncocytes, a fairly broad cytoplasm with finely granular or, in part, finely vacuolar structures and distinct cell membranes. The nuclei were predominantly round and moderately rich in chromatin but also in part, pyknotic. In paraffin-embedded sections the tumors could not be distinguished with certainty from chromophobe or moderately granulated acidophil adenomas. In plastic-embedded sections they could be identified by the typical filmy and finely granular feature of the cytoplasm which was distinctly different from conglomerations of secretory granules. Ultrastructurally they were characterized by many densely packed mitochondria. These were, in part, hydropically swollen. Furthermore, 5 tumors exhibited increased hormone-synthesizing organelles, 2 of which induced an acromegaly. Probably the oncocytic pituitary adenomas are secondarily transformed chromophobe or moderately chromophil tumors which must be regarded as independent, for the most part endocrinologically inactive pituitary tumors. In addition to these purely or almost purely oncocytic tumors further 12 adenomas (11.1%) with oncocytic parts constituting between 10 and 50% of the tissue were in our collection. Of these, 5 were moderately or distinctly acidophil adenomas with clinical symptoms of acromegaly; 2 were, for the most part, mucoid cell adenomas with Nelson's syndrome."} {"id": "PMID:175559", "title": "[Paracrystallic, intraplasmatic inclusion bodies in human hepatocytes: a structural analytic study (author's transl)].", "content": "Electron micrographs from intraplasmatic inclusion bodies of human hepatocytes are described; these paracrystallic aggregations consist of helically arranged filaments. All the observed periodic structures within these bodies can be indicated as originating from the same compound by the use of the Frauenhofer diffraction pattern. Concerning the genesis of these characteristically structured bodies two possibilities are discussed: 1. A special polymeric form of fibrinogen and fibrin built up in vivo. 2. Polymerization of a monomeric enzyme, for example, glutamate dehydrogenase, to paracrystallic bodies by fixation-dependent cross-linkages.", "contents": "[Paracrystallic, intraplasmatic inclusion bodies in human hepatocytes: a structural analytic study (author's transl)]. Electron micrographs from intraplasmatic inclusion bodies of human hepatocytes are described; these paracrystallic aggregations consist of helically arranged filaments. All the observed periodic structures within these bodies can be indicated as originating from the same compound by the use of the Frauenhofer diffraction pattern. Concerning the genesis of these characteristically structured bodies two possibilities are discussed: 1. A special polymeric form of fibrinogen and fibrin built up in vivo. 2. Polymerization of a monomeric enzyme, for example, glutamate dehydrogenase, to paracrystallic bodies by fixation-dependent cross-linkages."} {"id": "PMID:175560", "title": "Ultrastructures of glosso-palatal fusion after treatment of meclozine-hydrochloride.", "content": "The behavior of the epithelial cells on the tongue and palatal processes during glosso-palatal fusion induced by Meclozine-hydrochloride was investigated with light and electron microscopes. Microscopical observations revealed that; at two or three days after the administration, the palatal processes were approximating to the tongue, and the superficial cells on the lateral sides of tongue became swollen and to have inclusion bodies, and in the epithelium on the medial sides of palatal processes, some inclusion bodies appeared too. At the time of contact, the superficial epithelial cells of tongue tended to degenerate markedly, and these degenerating cells were dissociated from the epithelium, and concurrently, superficial layer of the palatal epithelium became to have a lot of inclusion bodies. Between the two tissues, attachment devices developed just after the contact, and then, the cells in the intervening epithelial lining fell into a degeneration gradually. As well known, Meclozine-hydrochloride is one of important miner tranquilizers. From the findings mentioned above, it seemed to be possible that a heterotopic fusion caused with this drug is a result of a destruction of embryonic epithelium on tongue and palatal processes at a certain stage of development.", "contents": "Ultrastructures of glosso-palatal fusion after treatment of meclozine-hydrochloride. The behavior of the epithelial cells on the tongue and palatal processes during glosso-palatal fusion induced by Meclozine-hydrochloride was investigated with light and electron microscopes. Microscopical observations revealed that; at two or three days after the administration, the palatal processes were approximating to the tongue, and the superficial cells on the lateral sides of tongue became swollen and to have inclusion bodies, and in the epithelium on the medial sides of palatal processes, some inclusion bodies appeared too. At the time of contact, the superficial epithelial cells of tongue tended to degenerate markedly, and these degenerating cells were dissociated from the epithelium, and concurrently, superficial layer of the palatal epithelium became to have a lot of inclusion bodies. Between the two tissues, attachment devices developed just after the contact, and then, the cells in the intervening epithelial lining fell into a degeneration gradually. As well known, Meclozine-hydrochloride is one of important miner tranquilizers. From the findings mentioned above, it seemed to be possible that a heterotopic fusion caused with this drug is a result of a destruction of embryonic epithelium on tongue and palatal processes at a certain stage of development."} {"id": "PMID:175561", "title": "Ultrastructural localization of plasma lipoproteins in human intracranial arteries.", "content": "The fine-structural localization of apoB, the major protein constituent of both the low and very low density plasma lipoprotein fractions, was described in human middle cerebral and basilar arteries. Using an immunoperoxidase technique together with electron microscopy, apoB was localized only in arteries with atherosclerotic involvement and to the following regions in these arteries: 1. on the outer aspects of extracellular spherical structures with diameters of 250 to 700 A found predominantly in lipid cores and between bands of collagen fibers of advanced atherosclerotic lesions; 2. on the surface of reduplicated elastica; 3. along collagen fibers and; 4. on aggregates of extracellular spherical lipid globules. These results suggest that the extracellular spheres may represent the fine-structural morphology of deposited low and very low density lipoproteins and that free apoB may be bound to lipid globules, elastica, and collagen fibers.", "contents": "Ultrastructural localization of plasma lipoproteins in human intracranial arteries. The fine-structural localization of apoB, the major protein constituent of both the low and very low density plasma lipoprotein fractions, was described in human middle cerebral and basilar arteries. Using an immunoperoxidase technique together with electron microscopy, apoB was localized only in arteries with atherosclerotic involvement and to the following regions in these arteries: 1. on the outer aspects of extracellular spherical structures with diameters of 250 to 700 A found predominantly in lipid cores and between bands of collagen fibers of advanced atherosclerotic lesions; 2. on the surface of reduplicated elastica; 3. along collagen fibers and; 4. on aggregates of extracellular spherical lipid globules. These results suggest that the extracellular spheres may represent the fine-structural morphology of deposited low and very low density lipoproteins and that free apoB may be bound to lipid globules, elastica, and collagen fibers."} {"id": "PMID:175563", "title": "The presence of complement fixing antibodies to Rous sarcoma virus (Schmidt-Ruppin strain) in patients with various forms of neoplasia.", "content": "The presence in men of antibodies to Rous sarcoma virus, an oncogenic virus of avian origin, was demonstrated. The highest antibody incidence was found in patients with various forms of cancer (34.4%, as against the value of 12% recorded in blood donors); these patients also showed an increased antibody level - 1/64 titers were detected in 43 out of 7 patients. The possibility of a human infection with animal oncogenic viruses is discussed, without excluding the hypothesis of a paraimmune reaction.", "contents": "The presence of complement fixing antibodies to Rous sarcoma virus (Schmidt-Ruppin strain) in patients with various forms of neoplasia. The presence in men of antibodies to Rous sarcoma virus, an oncogenic virus of avian origin, was demonstrated. The highest antibody incidence was found in patients with various forms of cancer (34.4%, as against the value of 12% recorded in blood donors); these patients also showed an increased antibody level - 1/64 titers were detected in 43 out of 7 patients. The possibility of a human infection with animal oncogenic viruses is discussed, without excluding the hypothesis of a paraimmune reaction."} {"id": "PMID:175565", "title": "[Effect of Polyakov's \"prints\" on the catalytic properties of an enzyme substrate system].", "content": "Silicagels, formed in presence of an enzyme (histidine decarboxylase from Micrococcus sp. n.), substrate (L-histidine-HCl-H2O) and inhibitor (imidazole) (so-called Polyakov's \"print\") exhibited specific catalytic properties in the reaction of L-histidine decarboxylation. The \"prints\" of the enzyme, inhibitor and substrate increased the activity of the enzyme-substrate system studied. The increased activity was probably due to the specific adsorption of imidazole ring of the substrate molecule by the \"print\".", "contents": "[Effect of Polyakov's \"prints\" on the catalytic properties of an enzyme substrate system]. Silicagels, formed in presence of an enzyme (histidine decarboxylase from Micrococcus sp. n.), substrate (L-histidine-HCl-H2O) and inhibitor (imidazole) (so-called Polyakov's \"print\") exhibited specific catalytic properties in the reaction of L-histidine decarboxylation. The \"prints\" of the enzyme, inhibitor and substrate increased the activity of the enzyme-substrate system studied. The increased activity was probably due to the specific adsorption of imidazole ring of the substrate molecule by the \"print\"."} {"id": "PMID:175567", "title": "[Fluorimetric ultramicrodetermination of the dansyl derivatives of cyclic 3'5-AMP by thin-layer chromatography].", "content": "A new fluoriemtric ultramicromethod was developed for quantiative determination of cyclic 3',5'-AMP as derivative of dansyl chloride using silica gel thin-layer chromatography. In presence of dansyl chloride cyclic 3',5'-AMP formed a fluorescent complex. A spot of dansyl derivative of cyclic 3',5'-AMP was photographed on a reversible colour film, after which the colour intensity of the spot on the film was determined directly by a special densitometer. Content of cyclic 3',5'-AMP was studied in different regions of rat brain. The in fluence of some psychotropic drugs on the level of cyclic 3',5'-AMP was studied using this method. The method was highly sensitive and reproducible and enabled to determine 10(-10) -- 10(-11) M cyclic 3',5'-AMP.", "contents": "[Fluorimetric ultramicrodetermination of the dansyl derivatives of cyclic 3'5-AMP by thin-layer chromatography]. A new fluoriemtric ultramicromethod was developed for quantiative determination of cyclic 3',5'-AMP as derivative of dansyl chloride using silica gel thin-layer chromatography. In presence of dansyl chloride cyclic 3',5'-AMP formed a fluorescent complex. A spot of dansyl derivative of cyclic 3',5'-AMP was photographed on a reversible colour film, after which the colour intensity of the spot on the film was determined directly by a special densitometer. Content of cyclic 3',5'-AMP was studied in different regions of rat brain. The in fluence of some psychotropic drugs on the level of cyclic 3',5'-AMP was studied using this method. The method was highly sensitive and reproducible and enabled to determine 10(-10) -- 10(-11) M cyclic 3',5'-AMP."} {"id": "PMID:175568", "title": "[Solubilization of cytochrome c in ischemic liver tissue].", "content": "Dynamics of cytochrome oxidase inactivation was studied in ischemic liver tissue using tetramethyl paraphenylene diamine (TMPD-oxidase) and cytochrome c (cytochrome c oxidase) as substrates. The cytochrome c ovidase activity was determined in presence of low concentrations (0.03%) of Triton X-100 (the total activity) and without the detergent (the free activity). Within 60 min after the restriction of oxygen supply to the liver tissue TMPD-oxidase was inactivated almost completely, at the same time cytochrome c oxidase maintained its activity. The free enzymatic activity became equal to the total activity; this phenomenon demonstrated an increased permeability of the external mitochondrial membrane for cytochrome c. The decrease in the TMPD-oxidase activity was considered to be due to the cytochrome c solubilization. This assumption was supported by the experiments, in which the addition of cytochrome c into the incubation mixture restored the enzymatic activity to the initial level. Hypotonic solutions and treatment of mitochondria with phospholipase A were found to simulate the impairment of the organelles in ischemic liver tissue. Increased peroxidation of unsaturated fatty acids in presence of ascorbic acid and ferrous ions was not accompanied by solubilization of cytochrome c.", "contents": "[Solubilization of cytochrome c in ischemic liver tissue]. Dynamics of cytochrome oxidase inactivation was studied in ischemic liver tissue using tetramethyl paraphenylene diamine (TMPD-oxidase) and cytochrome c (cytochrome c oxidase) as substrates. The cytochrome c ovidase activity was determined in presence of low concentrations (0.03%) of Triton X-100 (the total activity) and without the detergent (the free activity). Within 60 min after the restriction of oxygen supply to the liver tissue TMPD-oxidase was inactivated almost completely, at the same time cytochrome c oxidase maintained its activity. The free enzymatic activity became equal to the total activity; this phenomenon demonstrated an increased permeability of the external mitochondrial membrane for cytochrome c. The decrease in the TMPD-oxidase activity was considered to be due to the cytochrome c solubilization. This assumption was supported by the experiments, in which the addition of cytochrome c into the incubation mixture restored the enzymatic activity to the initial level. Hypotonic solutions and treatment of mitochondria with phospholipase A were found to simulate the impairment of the organelles in ischemic liver tissue. Increased peroxidation of unsaturated fatty acids in presence of ascorbic acid and ferrous ions was not accompanied by solubilization of cytochrome c."} {"id": "PMID:175566", "title": "[Stimulation by cyclic adenosine-3'5'-monophosphate by Na+, K+-activated ATPase from rabbit kidney].", "content": "Cyclic 3',5-AMP in vitro increased the activity of Na+, K+-ATPase, isolated from cortex and medulla of rabbit kidney. Maximal stimulating effect was observed in kidney cortex at 10(-6) M concentration and in medulla at 10(-4) M concentration of 3',5'-AMP. Under these conditions the enzymatic activity was increased by 24.6 +/- 4.1% and 27.9 +/- 7.7%, respectively. These data suggest that Na+, K+-ATPase, activated by cyclic 3',5'-AMP, is directly involved in the mechanism of Na+ transport in cells of osmoregulating organs.", "contents": "[Stimulation by cyclic adenosine-3'5'-monophosphate by Na+, K+-activated ATPase from rabbit kidney]. Cyclic 3',5-AMP in vitro increased the activity of Na+, K+-ATPase, isolated from cortex and medulla of rabbit kidney. Maximal stimulating effect was observed in kidney cortex at 10(-6) M concentration and in medulla at 10(-4) M concentration of 3',5'-AMP. Under these conditions the enzymatic activity was increased by 24.6 +/- 4.1% and 27.9 +/- 7.7%, respectively. These data suggest that Na+, K+-ATPase, activated by cyclic 3',5'-AMP, is directly involved in the mechanism of Na+ transport in cells of osmoregulating organs."} {"id": "PMID:175575", "title": "[Ultramorphometry of cells in a hamster embryo fibroblast culture following transformation by Rous sarcoma virus].", "content": "Changes in mitochondria, ergastoplasma and the polyribosomal apparatus of FHE (fibroblasts of hamster embryo) cell culture were studied in the kinetics of their malignification with Rous sarcoma virus. Considerable alterations were revealed in the organization of protein-synthetising cytoplasmic organells, manifested in the pronounced enhancement of nonspecific protein synthesis and reduction of ergastoplasma. This process starts immediately after the infection and shows a character approximating the exponents. On the part of the mitochondrial apparatus no differences between the experiment and control were revealed.", "contents": "[Ultramorphometry of cells in a hamster embryo fibroblast culture following transformation by Rous sarcoma virus]. Changes in mitochondria, ergastoplasma and the polyribosomal apparatus of FHE (fibroblasts of hamster embryo) cell culture were studied in the kinetics of their malignification with Rous sarcoma virus. Considerable alterations were revealed in the organization of protein-synthetising cytoplasmic organells, manifested in the pronounced enhancement of nonspecific protein synthesis and reduction of ergastoplasma. This process starts immediately after the infection and shows a character approximating the exponents. On the part of the mitochondrial apparatus no differences between the experiment and control were revealed."} {"id": "PMID:175571", "title": "[Effect of ACTH on the excretion of acid glycosaminoglycans in urine and on the content of haptoglobin in blood serum of rats in acute aseptic inflammation].", "content": "In aseptic inflammation an increase in excretion of acid glucosoaminoglycans with urine of rats was an earlier evidence for destructive processes in the main substance of connective tissues than an increase in content of haptoglobin in blood serum. The increase in content of haptoglobin in blood serum was probably caused by beginning reparative processes in the centre of impairment. The centre of inflammation, caused by subcutaneous administration of turpentine simultaneously with repeated injections of high doses of ACTH, was maintained in the rats longer than in animals, which were not treated with ACTH. In the case the most distinct increase in excretion of glycosoaminoglycans with urine was observed; content of haptoglobin was also increased in blood serum.", "contents": "[Effect of ACTH on the excretion of acid glycosaminoglycans in urine and on the content of haptoglobin in blood serum of rats in acute aseptic inflammation]. In aseptic inflammation an increase in excretion of acid glucosoaminoglycans with urine of rats was an earlier evidence for destructive processes in the main substance of connective tissues than an increase in content of haptoglobin in blood serum. The increase in content of haptoglobin in blood serum was probably caused by beginning reparative processes in the centre of impairment. The centre of inflammation, caused by subcutaneous administration of turpentine simultaneously with repeated injections of high doses of ACTH, was maintained in the rats longer than in animals, which were not treated with ACTH. In the case the most distinct increase in excretion of glycosoaminoglycans with urine was observed; content of haptoglobin was also increased in blood serum."} {"id": "PMID:175577", "title": "[A kinetic analysis of the growth of transplanted tumors and their metastasis].", "content": "Under study were kinetic regularities in development and incorporation of tritium labelled thymidine into cells of two experimental metastasizing tumors -- Zajdela ascites hepatoma and Walker carcinosarcoma, transplanted intratesticulary. Primary tumors and their metastases in regional lymph nodes show certain differences relative both to the rate of the process and intensity of the DNA synthesis, and relative number of cells with incorporated labelled thymidine.", "contents": "[A kinetic analysis of the growth of transplanted tumors and their metastasis]. Under study were kinetic regularities in development and incorporation of tritium labelled thymidine into cells of two experimental metastasizing tumors -- Zajdela ascites hepatoma and Walker carcinosarcoma, transplanted intratesticulary. Primary tumors and their metastases in regional lymph nodes show certain differences relative both to the rate of the process and intensity of the DNA synthesis, and relative number of cells with incorporated labelled thymidine."} {"id": "PMID:175578", "title": "A new serum lipoprotein associated erythrocyte antigen which reacts with a monoclonal IgM. The stored human red blood cell SHRBC antigen.", "content": "A monoclonal IgM (IgM) was found to react with stored human red blood cells (SHRBC) and human low density lipoprotein (LDL). IgM Re Fab fragment was reactive. SHRBC antigen was present, in a hidden state, in all fresh human ABO erythrocytes studies; it was not present in fresh or stored animal RBC. Cross reactivity of SHRBC and LDL antigens against IgM Re and IgM Re Fab was demonstrated. In contrast with SHRBC antigen, LDL antigen has no species specificity and was also found in rabbit and rat LDL. Furthermore, cross-reacting soluble inhibitors were also found in human saliva, and in a small molecule fraction issued from human and rabbit serum. The IgM Re also reacted with human and animal glomerular membrane. These findings are suggestive of two closely related but not identical antigens: a human specific SHRBC antigen and a LDL-associated, SHRBC-like antigen, which is a secreted, non-human specific substance. The former is part of the human RBC structure, the latter is a soluble molecule which may be found in saliva and in serum where it may be free or bound to LDL; it also binds to glomerular membranes.", "contents": "A new serum lipoprotein associated erythrocyte antigen which reacts with a monoclonal IgM. The stored human red blood cell SHRBC antigen. A monoclonal IgM (IgM) was found to react with stored human red blood cells (SHRBC) and human low density lipoprotein (LDL). IgM Re Fab fragment was reactive. SHRBC antigen was present, in a hidden state, in all fresh human ABO erythrocytes studies; it was not present in fresh or stored animal RBC. Cross reactivity of SHRBC and LDL antigens against IgM Re and IgM Re Fab was demonstrated. In contrast with SHRBC antigen, LDL antigen has no species specificity and was also found in rabbit and rat LDL. Furthermore, cross-reacting soluble inhibitors were also found in human saliva, and in a small molecule fraction issued from human and rabbit serum. The IgM Re also reacted with human and animal glomerular membrane. These findings are suggestive of two closely related but not identical antigens: a human specific SHRBC antigen and a LDL-associated, SHRBC-like antigen, which is a secreted, non-human specific substance. The former is part of the human RBC structure, the latter is a soluble molecule which may be found in saliva and in serum where it may be free or bound to LDL; it also binds to glomerular membranes."} {"id": "PMID:175573", "title": "[A modified method for phosphoribosyl pyrophosphate synthesis].", "content": "A modified method for synthesis of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and ATP in presence of ribose phosphate pyrophosphokinase (RPPPK) was developed. RPPPK was isolated from extracts of acetone powder of rabbit liver tissue, using alcohol fractionation of proteins. The protein fraction, containing RPPPK, was isolated at 35% saturation with 96% ethyl alcohol. The identification of the synthesized preparation of PRPP was carried out in enzymatic reaction with adenine- and inosine phosphoribosyl transferases, using labelled adenine and guanine. The obtained product of reaction (AMP and GMP) were precipitated with lantane chloride.", "contents": "[A modified method for phosphoribosyl pyrophosphate synthesis]. A modified method for synthesis of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and ATP in presence of ribose phosphate pyrophosphokinase (RPPPK) was developed. RPPPK was isolated from extracts of acetone powder of rabbit liver tissue, using alcohol fractionation of proteins. The protein fraction, containing RPPPK, was isolated at 35% saturation with 96% ethyl alcohol. The identification of the synthesized preparation of PRPP was carried out in enzymatic reaction with adenine- and inosine phosphoribosyl transferases, using labelled adenine and guanine. The obtained product of reaction (AMP and GMP) were precipitated with lantane chloride."} {"id": "PMID:175570", "title": "[Mechanism of changes in oxidative phosphorylation in the kidney in nephropathy caused by post-transfusion complications].", "content": "A decrease in cytochrome c oxidase activity was observed in kidney tissue within 40 min after the transfusion of incompatible blood; at the same time, the succinate dehydrogenase activity was not altered. Opposite ratios (as compared with normal kidney) of the enzymatic activities were found within 24 hrs after a heterohemotransfusion. An addition of 5 M succinate to the kidney homogenate in vitro or administration of the substance at a dose of 8 mg per 100 g of body weight in vivo caused an activation of free oxidation and a decrease of phosphorylation. The addition of 50 M succinate, combined with hexokinase and NADH2, into the homogenate distinctly increased both the rate of tissue respiration and the coupled phosphorylation.", "contents": "[Mechanism of changes in oxidative phosphorylation in the kidney in nephropathy caused by post-transfusion complications]. A decrease in cytochrome c oxidase activity was observed in kidney tissue within 40 min after the transfusion of incompatible blood; at the same time, the succinate dehydrogenase activity was not altered. Opposite ratios (as compared with normal kidney) of the enzymatic activities were found within 24 hrs after a heterohemotransfusion. An addition of 5 M succinate to the kidney homogenate in vitro or administration of the substance at a dose of 8 mg per 100 g of body weight in vivo caused an activation of free oxidation and a decrease of phosphorylation. The addition of 50 M succinate, combined with hexokinase and NADH2, into the homogenate distinctly increased both the rate of tissue respiration and the coupled phosphorylation."} {"id": "PMID:175572", "title": "[Effect of hydrocortisone on lipid composition of blood serum lipoproteins in the development of experimental atherosclerosis].", "content": "Single administration of hydrocortisone into rabbits with experimental atherosclerosis increased the content of atherogenous classes of lipoproteins (Low Density Lipoproteins (LDL) and Very Low Density Lipoproteins (VLDL) in the animals with distinct atheromatosis. Content of the lipoproteins was decreased in animals, which had no atheromatous alterations in aorta under the effect of atherogenous diet. Within 5 hrs after the single administration of hydrocortisone in rabbits with pronounced atheromatosis of aorta relative content of cholesterol was increased in the VLDL fraction. In rabbits, resistant to development of atheromatosis, composition of VLDL was not altered. Under the effect of hydrocortisone the LDL fraction fo lipid composition was altered in the direction of relative increase in triglycerides content. In the LDL fractions subfractions were observed, which were similar to the VLDL in their cholesterol/triglycerides ratios. The data obtained suggest that in blood plasma transformation of the lipoproteins was impaired under the effect of hydrocortisone. Hydrocortisone influenced the spectrum and lipid composition of lipoproteins in blood serum independently of the degree of hypercholesterolaemia.", "contents": "[Effect of hydrocortisone on lipid composition of blood serum lipoproteins in the development of experimental atherosclerosis]. Single administration of hydrocortisone into rabbits with experimental atherosclerosis increased the content of atherogenous classes of lipoproteins (Low Density Lipoproteins (LDL) and Very Low Density Lipoproteins (VLDL) in the animals with distinct atheromatosis. Content of the lipoproteins was decreased in animals, which had no atheromatous alterations in aorta under the effect of atherogenous diet. Within 5 hrs after the single administration of hydrocortisone in rabbits with pronounced atheromatosis of aorta relative content of cholesterol was increased in the VLDL fraction. In rabbits, resistant to development of atheromatosis, composition of VLDL was not altered. Under the effect of hydrocortisone the LDL fraction fo lipid composition was altered in the direction of relative increase in triglycerides content. In the LDL fractions subfractions were observed, which were similar to the VLDL in their cholesterol/triglycerides ratios. The data obtained suggest that in blood plasma transformation of the lipoproteins was impaired under the effect of hydrocortisone. Hydrocortisone influenced the spectrum and lipid composition of lipoproteins in blood serum independently of the degree of hypercholesterolaemia."} {"id": "PMID:175579", "title": "[2 types of oncornavirus viroins in epithelial cells from human milk].", "content": "Virions of types B and C similar to previously known mammal oncornaviruses were found in tissue cultures prepared from epithelial cells sedimented from the milk of a lactating woman with mammary cancer (HEC-31) and the milk of two clinically normal women (HEC-33 and HEC-34). In HEC-33 culture type C particles were predominant quantitatively. All the three milk specimens gave an identical precipitation line with antiserum for the milk of the mammary cancer patient as well as sequences forming molecular hybrids with DNA product of oncornavirus type D. At the same time, no positive immunologic reaction was obtained with the test system for oncornavirus type D from HEp-2 cells.", "contents": "[2 types of oncornavirus viroins in epithelial cells from human milk]. Virions of types B and C similar to previously known mammal oncornaviruses were found in tissue cultures prepared from epithelial cells sedimented from the milk of a lactating woman with mammary cancer (HEC-31) and the milk of two clinically normal women (HEC-33 and HEC-34). In HEC-33 culture type C particles were predominant quantitatively. All the three milk specimens gave an identical precipitation line with antiserum for the milk of the mammary cancer patient as well as sequences forming molecular hybrids with DNA product of oncornavirus type D. At the same time, no positive immunologic reaction was obtained with the test system for oncornavirus type D from HEp-2 cells."} {"id": "PMID:175580", "title": "[Development of poliovirus infection in laboratory animals of different species].", "content": "The capacity of vaccine and virulent strains of poliomyelitis virus to multiply in laboratory animals of different species was studied. Virus reproduction was judged by formation of photoresistant virus progeny in response to inoculation of the animals with photosensitized virus. Multiplication of virulent poliomyelitis virus strains observed in the majority of animal species examined (monkeys, newborn and adult cotton rats, newborn and adult white mice, chickens, chick embryos) resulted in active formation of photoresistant virus population and in some cases was accompanied by clinical symptoms of the disease. Multiplication of vaccine strains was observed in a smaller number of animal species and was limited, as a rule. Among non-primate animals, newborn cotton rats were most susceptible to poliovirus infection. Newborn guinea pigs were the only species of laboratory animals in which no multiplication of any of the six strains under study could be detected.", "contents": "[Development of poliovirus infection in laboratory animals of different species]. The capacity of vaccine and virulent strains of poliomyelitis virus to multiply in laboratory animals of different species was studied. Virus reproduction was judged by formation of photoresistant virus progeny in response to inoculation of the animals with photosensitized virus. Multiplication of virulent poliomyelitis virus strains observed in the majority of animal species examined (monkeys, newborn and adult cotton rats, newborn and adult white mice, chickens, chick embryos) resulted in active formation of photoresistant virus population and in some cases was accompanied by clinical symptoms of the disease. Multiplication of vaccine strains was observed in a smaller number of animal species and was limited, as a rule. Among non-primate animals, newborn cotton rats were most susceptible to poliovirus infection. Newborn guinea pigs were the only species of laboratory animals in which no multiplication of any of the six strains under study could be detected."} {"id": "PMID:175581", "title": "[Virological study of simian hemorrhagic fever].", "content": "The results of a comparative study of different routes of inoculation of simian hemorrhagic fever (SHF) virus to Macaca monkeys are presented as well as the results of virological examinations of sick animals. Only the parenteral route of inoculation has been found to be effective. After virus penetration, a long-term viremia and generalization of the infection are observed. The virus is found in the brain, the spinal cord and bone marrow, the spleen, the liver, the kidneys, the cerebrospinal fluid, the urine and nasopharyngeal washings. By the fluorescent antibody technique the virus-specific antigen is demonstrated in the capillary endothelium, neurons and glial cells of the brain, and in the reticulo-endothelial and macrophagal elements of parenchymatous organs.", "contents": "[Virological study of simian hemorrhagic fever]. The results of a comparative study of different routes of inoculation of simian hemorrhagic fever (SHF) virus to Macaca monkeys are presented as well as the results of virological examinations of sick animals. Only the parenteral route of inoculation has been found to be effective. After virus penetration, a long-term viremia and generalization of the infection are observed. The virus is found in the brain, the spinal cord and bone marrow, the spleen, the liver, the kidneys, the cerebrospinal fluid, the urine and nasopharyngeal washings. By the fluorescent antibody technique the virus-specific antigen is demonstrated in the capillary endothelium, neurons and glial cells of the brain, and in the reticulo-endothelial and macrophagal elements of parenchymatous organs."} {"id": "PMID:175582", "title": "[Use of the immunofluorescence test in the differential diagnosis of acute and latent adenovirus infections in adult].", "content": "Regular laboratory and clinical examinations were carried out in 150 patients with acute respiratory diseases and 25 normal subjects from family foci in whom adenovirus antigen was found in the epithelial cells of the nasal mucosa by means of the immunofluorescence test upon admission. By combinations of various laboratory methods adenovirus infection was confirmed in all the subjects under study. In preparations obtained from normal subjects, predominantly nuclear localization of adenovirus antigen was observed. In patients, localization of the antigen varied. Detection of cells with nuclear localization of adenovirus antigen, the regularity of this localization and the duration of this finding suggest latent infection, whereas findings of cells with cytoplasmic localization of the antigen and an increase in the number of such cells in the course of the disease suggest active adenovirus infection.", "contents": "[Use of the immunofluorescence test in the differential diagnosis of acute and latent adenovirus infections in adult]. Regular laboratory and clinical examinations were carried out in 150 patients with acute respiratory diseases and 25 normal subjects from family foci in whom adenovirus antigen was found in the epithelial cells of the nasal mucosa by means of the immunofluorescence test upon admission. By combinations of various laboratory methods adenovirus infection was confirmed in all the subjects under study. In preparations obtained from normal subjects, predominantly nuclear localization of adenovirus antigen was observed. In patients, localization of the antigen varied. Detection of cells with nuclear localization of adenovirus antigen, the regularity of this localization and the duration of this finding suggest latent infection, whereas findings of cells with cytoplasmic localization of the antigen and an increase in the number of such cells in the course of the disease suggest active adenovirus infection."} {"id": "PMID:175585", "title": "[Preparation of immune serums for the identification of rhinoviruses].", "content": "Six schedules of immunization of rabbits, guinea pigs and rats for production of antirhinovirus immune sera were studied. Sera with virus-neutralizing antibody titers of 1:1000 to 1:50,000 were obtained in rabbits immunized into popliteal lymph nodes. The resulting sera had high titers of antibody to cell components and neutralized the cytopathic effect induced by heterologous strains. Sera from which cell components had been absorbed showed strict type-specificity in the neutralization and indirect immunofluorescent tests. A mixture of sera has been shown to be useful for identification of rhinoviruses by the immunofluorescent procedure.", "contents": "[Preparation of immune serums for the identification of rhinoviruses]. Six schedules of immunization of rabbits, guinea pigs and rats for production of antirhinovirus immune sera were studied. Sera with virus-neutralizing antibody titers of 1:1000 to 1:50,000 were obtained in rabbits immunized into popliteal lymph nodes. The resulting sera had high titers of antibody to cell components and neutralized the cytopathic effect induced by heterologous strains. Sera from which cell components had been absorbed showed strict type-specificity in the neutralization and indirect immunofluorescent tests. A mixture of sera has been shown to be useful for identification of rhinoviruses by the immunofluorescent procedure."} {"id": "PMID:175590", "title": "[The role of cyclic AMP and Ca in the altered permeability of tumour cells grown with a deficiency of Mg].", "content": "Yoshida-Ascites tumour cells grown with a deficiency of Mg show an increased passive permeability. This results in an accelerated efflux of Na+. The uptake of aminobutyric acid is decreased, while its release is unchanged. The uptake and release of alpha-methylglucopyranoside are unchanged. In the cells grown with a deficiency of Mg, the concentration of cyclic AMP is slightly increased. The addition of dibutyryl cyclic AMP results in similar but smaller changes in the cellular concentration of cations, to those found in Mg deficiency. It is suggested that the effects of Mg deficiency result from the action of cyclic AMP and/or an increase in the Ca concentration of the cell.", "contents": "[The role of cyclic AMP and Ca in the altered permeability of tumour cells grown with a deficiency of Mg]. Yoshida-Ascites tumour cells grown with a deficiency of Mg show an increased passive permeability. This results in an accelerated efflux of Na+. The uptake of aminobutyric acid is decreased, while its release is unchanged. The uptake and release of alpha-methylglucopyranoside are unchanged. In the cells grown with a deficiency of Mg, the concentration of cyclic AMP is slightly increased. The addition of dibutyryl cyclic AMP results in similar but smaller changes in the cellular concentration of cations, to those found in Mg deficiency. It is suggested that the effects of Mg deficiency result from the action of cyclic AMP and/or an increase in the Ca concentration of the cell."} {"id": "PMID:175591", "title": "[Biochemical investigations of cancer cachexia: I. Tumour induced changes of glycogenolysis and gluconeogenesis of Walker carcinoma bearing rats (author's transl)].", "content": "Rats (weight 150-200 g) bearing Walker-carcinoma showed tumour size dependent hypoglycemia, diminished mobilization of glycogen following glucagon stimulation and elevated values of the enzyme activity of glucose-6-(P)-ase. A further hormonal stimulation of this enzyme activity towards the values observed in normal rats after betamethasone stimulation was not possible. The values of the enzyme fructose-1,6-di-(P)-ase in liver of tumour bearing rats equalled those found in normal controls and did not show any rise after application of betamethasone. The serum levels of free fatty acids did not show any difference between normal controls and tumour bearing rats, and displayed an equal rise after intensive stimulation of peripheral lipolysis.", "contents": "[Biochemical investigations of cancer cachexia: I. Tumour induced changes of glycogenolysis and gluconeogenesis of Walker carcinoma bearing rats (author's transl)]. Rats (weight 150-200 g) bearing Walker-carcinoma showed tumour size dependent hypoglycemia, diminished mobilization of glycogen following glucagon stimulation and elevated values of the enzyme activity of glucose-6-(P)-ase. A further hormonal stimulation of this enzyme activity towards the values observed in normal rats after betamethasone stimulation was not possible. The values of the enzyme fructose-1,6-di-(P)-ase in liver of tumour bearing rats equalled those found in normal controls and did not show any rise after application of betamethasone. The serum levels of free fatty acids did not show any difference between normal controls and tumour bearing rats, and displayed an equal rise after intensive stimulation of peripheral lipolysis."} {"id": "PMID:175592", "title": "Attempts to induce tubular deformations and subsequent mixed tumours from organotypic cultures of mouse renal mesenchyma.", "content": "With the aim of expanding knowledge on the pathogenesis of nephroblastomata, an embryological organ culture system (Grobstein, 1956) was tested for its applicability to in vitro carcinogenesis experiments by using murine sarcoma virus (MSV-M) and 3-methylcholanthrene (MCA). Treatment of CBA/H-T6 mouse metanephrogenic mesenchyma with MSV-M at the pretubular stage neither disturbed the glomerulogenesis nor induced rapid malignant transformation. Treatment of the same tissues with MCA considerably inhibited the glomerulogenesis but failed to also reduce rapid malignant transformation. However, one MSV-M, one MCA and two untreated cultures showed malignant transformation after prolonged survival in vitro and produced different histological types of tumours upon transplantation into newborn CBA/H-T6 mice.", "contents": "Attempts to induce tubular deformations and subsequent mixed tumours from organotypic cultures of mouse renal mesenchyma. With the aim of expanding knowledge on the pathogenesis of nephroblastomata, an embryological organ culture system (Grobstein, 1956) was tested for its applicability to in vitro carcinogenesis experiments by using murine sarcoma virus (MSV-M) and 3-methylcholanthrene (MCA). Treatment of CBA/H-T6 mouse metanephrogenic mesenchyma with MSV-M at the pretubular stage neither disturbed the glomerulogenesis nor induced rapid malignant transformation. Treatment of the same tissues with MCA considerably inhibited the glomerulogenesis but failed to also reduce rapid malignant transformation. However, one MSV-M, one MCA and two untreated cultures showed malignant transformation after prolonged survival in vitro and produced different histological types of tumours upon transplantation into newborn CBA/H-T6 mice."} {"id": "PMID:175593", "title": "[Transplantable sebaceous adenoma of the mouse with virus particles studied by electron microscopy (author's transl)].", "content": "Histology and ultrastructure of a sebaceous adenoma of the mouse -- derived from i.p.-injection of 0.1 ml DNA, isolated from cells of a transplantable mouse-leukemia -- were studied. The original tumour and all transplanted tumours display the same tissular differentiation. In all tumours virus particles were found. Structure and behaviour of the intracytoplasmic A-particles resemble those of the mouse mammary tumour virus while the C-particles found extracellular were identical with the leukemia viruses of the mouse. It might be suspected that mammary tumour virus and leukemia viruses are either non specific or that a new virus is present in the sebaceous adenoma.", "contents": "[Transplantable sebaceous adenoma of the mouse with virus particles studied by electron microscopy (author's transl)]. Histology and ultrastructure of a sebaceous adenoma of the mouse -- derived from i.p.-injection of 0.1 ml DNA, isolated from cells of a transplantable mouse-leukemia -- were studied. The original tumour and all transplanted tumours display the same tissular differentiation. In all tumours virus particles were found. Structure and behaviour of the intracytoplasmic A-particles resemble those of the mouse mammary tumour virus while the C-particles found extracellular were identical with the leukemia viruses of the mouse. It might be suspected that mammary tumour virus and leukemia viruses are either non specific or that a new virus is present in the sebaceous adenoma."} {"id": "PMID:175594", "title": "35S incorporation into sulfated mucopolysaccharides from embryonic, normal, and neoplastic liver cells.", "content": "The incorporation of 35S into the sulfated mucopolysaccharides from hepatoma, normal and embryonic liver cells has been studied by means of anion exchange chromatography of the isolated mucopolysaccharide. Comparatively to liver cells, while showing a higher labeling of low sulfated mucopolysaccharides the hepatoma cells incorporate much less 35S into the heparin fraction.", "contents": "35S incorporation into sulfated mucopolysaccharides from embryonic, normal, and neoplastic liver cells. The incorporation of 35S into the sulfated mucopolysaccharides from hepatoma, normal and embryonic liver cells has been studied by means of anion exchange chromatography of the isolated mucopolysaccharide. Comparatively to liver cells, while showing a higher labeling of low sulfated mucopolysaccharides the hepatoma cells incorporate much less 35S into the heparin fraction."} {"id": "PMID:175595", "title": "[Pathogenesis of neural lesions in Marek's disease. II. Transmission of neural lesions by spleen cells from ill donors (author's transl) ].", "content": "Viable spleen lymphocytes of 13 chickens with clinical and histological signs of Marek's disease were transferred by intravenous injection to 46 chickens 4-10 days old, X-rayed 24 hours before inoculation. Histologically Marek-like neural lesions were almost regularly observed in the chickens after 6-14 days. Chickens having received destroyed spleen lymphocytes of Marek-donors were free of nerve infiltrations. There were also no neural lesions detectable within 14 days after application of pathogenic Marek's disease virus alone, or in combination with viable spleen cells from healthy donors immunized against Marek's disease. These results exclude that the formation of neural lesions 6-14 days following the spleen cell transfer is solely induced by the virus.", "contents": "[Pathogenesis of neural lesions in Marek's disease. II. Transmission of neural lesions by spleen cells from ill donors (author's transl) ]. Viable spleen lymphocytes of 13 chickens with clinical and histological signs of Marek's disease were transferred by intravenous injection to 46 chickens 4-10 days old, X-rayed 24 hours before inoculation. Histologically Marek-like neural lesions were almost regularly observed in the chickens after 6-14 days. Chickens having received destroyed spleen lymphocytes of Marek-donors were free of nerve infiltrations. There were also no neural lesions detectable within 14 days after application of pathogenic Marek's disease virus alone, or in combination with viable spleen cells from healthy donors immunized against Marek's disease. These results exclude that the formation of neural lesions 6-14 days following the spleen cell transfer is solely induced by the virus."} {"id": "PMID:175596", "title": "Reactions of essential sulfhydryl residues of dehydrogenases with nicotinamide-(S-methylmercury-thioinosine) dinucleotide.", "content": "Nicotinamide-(S-methylmercury-thioinosine) dinucleotide was formed by reaction of nicotinamide-(6-thiopurine) dinucleotide with methylmercury chloride. The compound exhibits coenzyme properties in the test with LDH (Km=1.5 X 10(-4) M, Vmax=12500) and LADH (Km=1.7 X 10(-4) M, Vmax=27) and inactivates YADH and GAPDH. From incubations with LDH and LADH the mercury containing coenzyme could be regarded by column be qualified for the X-ray structure analysis of the coenzyme-enzyme complex for some dehyrogenases based on the proportion of the heavy metal.", "contents": "Reactions of essential sulfhydryl residues of dehydrogenases with nicotinamide-(S-methylmercury-thioinosine) dinucleotide. Nicotinamide-(S-methylmercury-thioinosine) dinucleotide was formed by reaction of nicotinamide-(6-thiopurine) dinucleotide with methylmercury chloride. The compound exhibits coenzyme properties in the test with LDH (Km=1.5 X 10(-4) M, Vmax=12500) and LADH (Km=1.7 X 10(-4) M, Vmax=27) and inactivates YADH and GAPDH. From incubations with LDH and LADH the mercury containing coenzyme could be regarded by column be qualified for the X-ray structure analysis of the coenzyme-enzyme complex for some dehyrogenases based on the proportion of the heavy metal."} {"id": "PMID:175600", "title": "The ultrastructure of macrogametes of Eimeria ferrisi Levine and Ivens 1965 in Mus musculus.", "content": "Macrogametes of Eimeria ferrisi occurred in epithelial cells of the cecum and colon of Mus musculus and were studied by electron microscopy. Young stages were identified as macrogamonts by the presence of wall-forming bodies. At first an outerlimiting membrane and remnants of the inner membrane complex of the former merozoite pellicle were present; the latter was later lost but in mature macrogametes 3 limiting membranes were observed. Type II wall-forming bodies appeared before type I; the former developed in expanded cisternae of the endoplasmic reticulum whereas the latter were smaller in size and appeared in the ground substance of the cytoplasm. After formation of the oocyst wall the bodies of the 2 types were no longer visible. The presenceodies of the 2 types were no longer visible. The persistence of micronemes in mature macrogametes and the presence of numerous layers of rough endoplasmic reticulum during wall formation have not been previously reported.", "contents": "The ultrastructure of macrogametes of Eimeria ferrisi Levine and Ivens 1965 in Mus musculus. Macrogametes of Eimeria ferrisi occurred in epithelial cells of the cecum and colon of Mus musculus and were studied by electron microscopy. Young stages were identified as macrogamonts by the presence of wall-forming bodies. At first an outerlimiting membrane and remnants of the inner membrane complex of the former merozoite pellicle were present; the latter was later lost but in mature macrogametes 3 limiting membranes were observed. Type II wall-forming bodies appeared before type I; the former developed in expanded cisternae of the endoplasmic reticulum whereas the latter were smaller in size and appeared in the ground substance of the cytoplasm. After formation of the oocyst wall the bodies of the 2 types were no longer visible. The presenceodies of the 2 types were no longer visible. The persistence of micronemes in mature macrogametes and the presence of numerous layers of rough endoplasmic reticulum during wall formation have not been previously reported."} {"id": "PMID:175597", "title": "Electronic structure and spatial arrangement of C2v-coordinated ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin.", "content": "The electronic term scheme of ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin is evaluated by a Hamiltonian which involves the Coulomb repulsion of the 3d electrons, their interaction with the C2v-coordinated ligands, and spin-orbit coupling. The adjustable parameters of the theory were determined by a least squares fit to experimental EPR, susceptibility, and far-infrared data reported in the literature. According to these results, the structural properties of the ferric ion and its neighboring ligands were discussed by means of group theoretical arguments: An increasing out of plane position of the ferric ion is found in the sequence metHb--metMb--MbF which corresponds to an increasing binding strength with the axial ligands.", "contents": "Electronic structure and spatial arrangement of C2v-coordinated ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin. The electronic term scheme of ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin is evaluated by a Hamiltonian which involves the Coulomb repulsion of the 3d electrons, their interaction with the C2v-coordinated ligands, and spin-orbit coupling. The adjustable parameters of the theory were determined by a least squares fit to experimental EPR, susceptibility, and far-infrared data reported in the literature. According to these results, the structural properties of the ferric ion and its neighboring ligands were discussed by means of group theoretical arguments: An increasing out of plane position of the ferric ion is found in the sequence metHb--metMb--MbF which corresponds to an increasing binding strength with the axial ligands."} {"id": "PMID:175601", "title": "[Ischemic contractures of muscle and nerve lesions (author's transl)].", "content": "Reporting 14 own cases symptomatology and treatment of the common ischemic syndromes of the extremities (Volkmann's contracture, thumb adduction contracture respectively contracture of the intrinsic hand muscles and anterior tibial syndrome) including the regularly concomitant nerve lesions are discussed. Edema and compression beyond the primary ischemia are essential factors in pathogenesis of nerve and muscle lesions. The electromyographic examination is helpful in diagnosis, prognosis and treatment of the severe sequelae of nerve and muscle. Since late diagnosis yields poor therapeutical results, early recognition of ischemic states and prophylaxis are most important.", "contents": "[Ischemic contractures of muscle and nerve lesions (author's transl)]. Reporting 14 own cases symptomatology and treatment of the common ischemic syndromes of the extremities (Volkmann's contracture, thumb adduction contracture respectively contracture of the intrinsic hand muscles and anterior tibial syndrome) including the regularly concomitant nerve lesions are discussed. Edema and compression beyond the primary ischemia are essential factors in pathogenesis of nerve and muscle lesions. The electromyographic examination is helpful in diagnosis, prognosis and treatment of the severe sequelae of nerve and muscle. Since late diagnosis yields poor therapeutical results, early recognition of ischemic states and prophylaxis are most important."} {"id": "PMID:175598", "title": "Interaction between dehydrogenases and a new NAD -isomer.", "content": "A new NAD -isomer was prepared, in which the D-ribose of the adenosine moiety was substituted by the enantiomeric L-ribose. As compared to nicotinamide-adenine-dinucleotide (NAD) and NADH the coenzyme isomer (D,L)-NAD and its dihydroform (D,L)-NADH are far less tightly bound to lactate dehydrogenase and alcohol dehydrogenase from horse liver. In the presence of the second substrate (D,L)-NAD and (D,L)-NADH act as hydrogen acceptor and hydrogen donator, respectively, with lactate dehydrogenase and alcohol dehydrogenases from horse liver and yeast. Compared to NAD and NADH the Michaelis constants are always increased, the catalytic constants (V/Et) were found to be decreased except for the dihydroform reacting with alcohol dehydrogenase from liver.", "contents": "Interaction between dehydrogenases and a new NAD -isomer. A new NAD -isomer was prepared, in which the D-ribose of the adenosine moiety was substituted by the enantiomeric L-ribose. As compared to nicotinamide-adenine-dinucleotide (NAD) and NADH the coenzyme isomer (D,L)-NAD and its dihydroform (D,L)-NADH are far less tightly bound to lactate dehydrogenase and alcohol dehydrogenase from horse liver. In the presence of the second substrate (D,L)-NAD and (D,L)-NADH act as hydrogen acceptor and hydrogen donator, respectively, with lactate dehydrogenase and alcohol dehydrogenases from horse liver and yeast. Compared to NAD and NADH the Michaelis constants are always increased, the catalytic constants (V/Et) were found to be decreased except for the dihydroform reacting with alcohol dehydrogenase from liver."} {"id": "PMID:175602", "title": "[Peripheral nerve injury due to total replacement of the hip-joint (author's transl)].", "content": "Report on peripheral nerve lesions due to total replacement of the hip-joint based on the literature and the authors' own experience. In 15 patients our diagnosis was made on clinical and electromyographic evidence. 16 endoprostheses had been inserted. The femoral nerve was involved on 12 occasions, the sciatic in 5, the glutei in 5, the obturator in 2, the lateral cutaneous femoris in 2 and the posterior cutaneous in 1 instances. One has to count on about 1% of such lesions. This type of paresis has to be distingushed from pseudopareses for which electromyography was proved very effective. Damage due to overstretching is probably the main cause. Treatment with thorough physiotherapy and faradic stimulation is needed. When this is done the prognosis is generally favourable. In some cases, however, these complications may limit the success of the operation and postoperative disability may be worse than before.", "contents": "[Peripheral nerve injury due to total replacement of the hip-joint (author's transl)]. Report on peripheral nerve lesions due to total replacement of the hip-joint based on the literature and the authors' own experience. In 15 patients our diagnosis was made on clinical and electromyographic evidence. 16 endoprostheses had been inserted. The femoral nerve was involved on 12 occasions, the sciatic in 5, the glutei in 5, the obturator in 2, the lateral cutaneous femoris in 2 and the posterior cutaneous in 1 instances. One has to count on about 1% of such lesions. This type of paresis has to be distingushed from pseudopareses for which electromyography was proved very effective. Damage due to overstretching is probably the main cause. Treatment with thorough physiotherapy and faradic stimulation is needed. When this is done the prognosis is generally favourable. In some cases, however, these complications may limit the success of the operation and postoperative disability may be worse than before."} {"id": "PMID:175599", "title": "In vitro transformation of chicken bone marrow cells with avian erythroblastosis virus.", "content": "An in vitro transformation of bone marrow cells has been demonstrated for two strains of avian erythroblastosis virus (AEV-R and AEV-ES4). The transformed cells were indistinguishable from in vivo transformed erythroblasts in morphology and staining characteristics and could be propagated to large numbers. The transformation efficiency could be greatly increased by the addition of dimethylsulfoxide (DMSO). The number of foci appearing in the presence of DMSO was proportional to the virus concentration.", "contents": "In vitro transformation of chicken bone marrow cells with avian erythroblastosis virus. An in vitro transformation of bone marrow cells has been demonstrated for two strains of avian erythroblastosis virus (AEV-R and AEV-ES4). The transformed cells were indistinguishable from in vivo transformed erythroblasts in morphology and staining characteristics and could be propagated to large numbers. The transformation efficiency could be greatly increased by the addition of dimethylsulfoxide (DMSO). The number of foci appearing in the presence of DMSO was proportional to the virus concentration."} {"id": "PMID:175612", "title": "[Isolation of \"pregnancy-zone\" proteins using immuno absorbents and study of possible enzyme activities].", "content": "The purification of the pregnancy zone protein by means of immunoadsorbents is described. The pregnancy zone protein antibody was isolated from an absorbed rabbit antiserum and coupled with CNBr-activated sepharose. The pregnancy zone protein was isolated from pregnancy serum by the specific antibody cross-linked with sepharose. Contaminating serum proteins were eliminated by \"inverse\" immunoadsorption using antibodies against these proteins coupled with sepharose. An immunoelectrophoretically pure pregnancy zone protein was obtained. By means of a combination of immunoprecipitation and enzyme reaction in agar gel could be excluded that the pregnancy zone protein possesses activities of the following 11 enzymes: ceruloplasmin, leucine amino peptidase, alkaline phosphatase, carboxylic esterase, lactate dehydrogenase, malate dehydrogenase, glycerophosphate dehydrogenase, glucose-6-phosphat-dehydrogenase, cholinesterase, acetyl cholinesterase and oxytocinase.", "contents": "[Isolation of \"pregnancy-zone\" proteins using immuno absorbents and study of possible enzyme activities]. The purification of the pregnancy zone protein by means of immunoadsorbents is described. The pregnancy zone protein antibody was isolated from an absorbed rabbit antiserum and coupled with CNBr-activated sepharose. The pregnancy zone protein was isolated from pregnancy serum by the specific antibody cross-linked with sepharose. Contaminating serum proteins were eliminated by \"inverse\" immunoadsorption using antibodies against these proteins coupled with sepharose. An immunoelectrophoretically pure pregnancy zone protein was obtained. By means of a combination of immunoprecipitation and enzyme reaction in agar gel could be excluded that the pregnancy zone protein possesses activities of the following 11 enzymes: ceruloplasmin, leucine amino peptidase, alkaline phosphatase, carboxylic esterase, lactate dehydrogenase, malate dehydrogenase, glycerophosphate dehydrogenase, glucose-6-phosphat-dehydrogenase, cholinesterase, acetyl cholinesterase and oxytocinase."} {"id": "PMID:175613", "title": "[Formation and persistence of latex-agglutination-inhibiting IgG- and IgM-antibodies in rabbits inoculated with poliomyelitis, Coxsackie and encephalomyocarditis viruses (author's transl)].", "content": "The formation and presistence of virus specific IgG- and IgM-antibodies produced in rabbits after a single dose of poliomyelitisvirus, coxsackievirus or encephalomyocarditisvirus were tested comparatively by latex-agglutination-inhibition test, hemagglutination-inhibition test and neutralization test. The animals were immunized either intravenously alone or with Freund's complete adjuvant. The IgM-antibodies were only detectable for a short time by the three tests. In the IgG-fraction and in the unfractionated serum the neutralizing antibodies persisted without any loss in titer during the period observed, whereas the latex-agglutination-inhibiting and hemagglutination-inhibiting antibodies showed a significant decrease. The hemagglutination-inhibiting antibodies required 23 weeks (Figure 5), the latex-agglutination-inhibiting antibodies 7 weeks (without Freund's complete adjuvant; Figure 1 and 3) or about 16 weeks (with Freund's complete adjuvant; Figure 2, 4 and 5) respectively to decline to 25% of their maximum titer.", "contents": "[Formation and persistence of latex-agglutination-inhibiting IgG- and IgM-antibodies in rabbits inoculated with poliomyelitis, Coxsackie and encephalomyocarditis viruses (author's transl)]. The formation and presistence of virus specific IgG- and IgM-antibodies produced in rabbits after a single dose of poliomyelitisvirus, coxsackievirus or encephalomyocarditisvirus were tested comparatively by latex-agglutination-inhibition test, hemagglutination-inhibition test and neutralization test. The animals were immunized either intravenously alone or with Freund's complete adjuvant. The IgM-antibodies were only detectable for a short time by the three tests. In the IgG-fraction and in the unfractionated serum the neutralizing antibodies persisted without any loss in titer during the period observed, whereas the latex-agglutination-inhibiting and hemagglutination-inhibiting antibodies showed a significant decrease. The hemagglutination-inhibiting antibodies required 23 weeks (Figure 5), the latex-agglutination-inhibiting antibodies 7 weeks (without Freund's complete adjuvant; Figure 1 and 3) or about 16 weeks (with Freund's complete adjuvant; Figure 2, 4 and 5) respectively to decline to 25% of their maximum titer."} {"id": "PMID:175614", "title": "Studies on the energetic metabolism of Shigella flexneri x Escherichia coli hybrids devoid of penetration ability. III. Catalase and phosphatase activity.", "content": "The catalase and phosphatase activity of avirulent by keratoconjunctival test of guinea pigs lac+, kcp- hybrids that have lost their ability of penetrating in the epithelium, received from virulent strains Shigella flexneri (Sh. flexneri 222 5a and Sh. flexneri M42-43) and donor strains Escherichia coli (E. coli K-12, P4x and E. coli H) was investigated. It was established that there is no any dependence between the lost of virulence of the hybrids and the level of the catalase activity. During the study of the phosphatase activity it was established, that in comparison with the recipient virulent shigella strains, the investigated avirulent lac+-hybrids revealed higher values of the enzyme activity.", "contents": "Studies on the energetic metabolism of Shigella flexneri x Escherichia coli hybrids devoid of penetration ability. III. Catalase and phosphatase activity. The catalase and phosphatase activity of avirulent by keratoconjunctival test of guinea pigs lac+, kcp- hybrids that have lost their ability of penetrating in the epithelium, received from virulent strains Shigella flexneri (Sh. flexneri 222 5a and Sh. flexneri M42-43) and donor strains Escherichia coli (E. coli K-12, P4x and E. coli H) was investigated. It was established that there is no any dependence between the lost of virulence of the hybrids and the level of the catalase activity. During the study of the phosphatase activity it was established, that in comparison with the recipient virulent shigella strains, the investigated avirulent lac+-hybrids revealed higher values of the enzyme activity."} {"id": "PMID:175615", "title": "[Aeromonas punctata subsp. caviae as the causative agent of acute gastroenteritis (author's transl)].", "content": "Since in the past, Aeromonas hydrophila had been isolated from all cases of human infection described. A. punctata and the anaerogenic sub-species were considered as apathogenic. From the case described, a close association between acute diarrhea with vomiting and the identification of A. punctata subsp. caviae becomes evident so that a conditional pathogenicity of this sub-species must be assumed. The question is discussed whether a preceding disturbance of the intestinal habitat in the presence of a particular susceptibility of the gastrointestinal tract promoted gastro-enteritis. Infection may have been brought about by the ingestion of surface water contaminated by sewage. Attention is again drawn to the fact that in the case of enteritis occuring during the open-air bathing season, faeces samples should also be examined for their Aeromonas content which may be performed by a simple indophenol or so-called cytochrome oxidase reaction of the aerobic flora in feces by rubbing off colonies into a corresponding test strip.", "contents": "[Aeromonas punctata subsp. caviae as the causative agent of acute gastroenteritis (author's transl)]. Since in the past, Aeromonas hydrophila had been isolated from all cases of human infection described. A. punctata and the anaerogenic sub-species were considered as apathogenic. From the case described, a close association between acute diarrhea with vomiting and the identification of A. punctata subsp. caviae becomes evident so that a conditional pathogenicity of this sub-species must be assumed. The question is discussed whether a preceding disturbance of the intestinal habitat in the presence of a particular susceptibility of the gastrointestinal tract promoted gastro-enteritis. Infection may have been brought about by the ingestion of surface water contaminated by sewage. Attention is again drawn to the fact that in the case of enteritis occuring during the open-air bathing season, faeces samples should also be examined for their Aeromonas content which may be performed by a simple indophenol or so-called cytochrome oxidase reaction of the aerobic flora in feces by rubbing off colonies into a corresponding test strip."} {"id": "PMID:175616", "title": "Serologic examination of birds from the area of Southern Moravia for the presence of antibodies against arboviruses of the groups alfa, flavo, Bunyamwera supergroup, and the virus Yaba 1-Lednice 110. I. Domestic fowls.", "content": "196 geese, 141 ducks, and 100 hens from 9 localities of the South Moravian region (District of Breclav) were examined by means of the haemagglutination-inhibition test (HIT) for the presence of antibodies against 12 arbovirus antigens of the groups Alfavirus (Western Equine Encephalitis (WEE), Eastern Equine Encephalitis (EEE), Semliki, Sindbis, Chikungunya, O'nyong-nyong), Flavovirus (Tick-borne Encephalitis (TBE), Dengue and West Nile Virus (WN), Bunyamwera Supergroup (Tahna and Beta Calovo), and the Yaba 1-Lednice 110 Virus. In tested fowls antibodies were mostly found against Yaba 1-Lednice 110 Virus, namely 3.6% in geese and 17.7% in ducks. Antibodies against Calovo Virus were found in only 1 of the tested ducks. All sera of hens were negative. Antibodies against arboviruses of the Alfa-and Flavovirus groups were not detected.", "contents": "Serologic examination of birds from the area of Southern Moravia for the presence of antibodies against arboviruses of the groups alfa, flavo, Bunyamwera supergroup, and the virus Yaba 1-Lednice 110. I. Domestic fowls. 196 geese, 141 ducks, and 100 hens from 9 localities of the South Moravian region (District of Breclav) were examined by means of the haemagglutination-inhibition test (HIT) for the presence of antibodies against 12 arbovirus antigens of the groups Alfavirus (Western Equine Encephalitis (WEE), Eastern Equine Encephalitis (EEE), Semliki, Sindbis, Chikungunya, O'nyong-nyong), Flavovirus (Tick-borne Encephalitis (TBE), Dengue and West Nile Virus (WN), Bunyamwera Supergroup (Tahna and Beta Calovo), and the Yaba 1-Lednice 110 Virus. In tested fowls antibodies were mostly found against Yaba 1-Lednice 110 Virus, namely 3.6% in geese and 17.7% in ducks. Antibodies against Calovo Virus were found in only 1 of the tested ducks. All sera of hens were negative. Antibodies against arboviruses of the Alfa-and Flavovirus groups were not detected."} {"id": "PMID:175617", "title": "Receptor for 5alpha-dihydrotestosterone from Streptomyces hydrogenans.", "content": "Streptomyces hydrogenans exhibits binding activity for 5alpha-dihydrotestosterone (17 beta-hydroxy-5alpha-androstan-3-one) in vivo. A cell free homogenate from the microorganism binds 5alpha-dihydrotestosterone in vitro as well. The association constant is 10(8) M-1 at 4 degrees C. Progesterone, but neither testerone nor cyproterone, competes with 5alpha-dihydrotestosterone for binding. The binding fraction from Streptomyces hydrogenans permits a simple assay for 5 alpha-dihydrotestosterone in biological samples.", "contents": "Receptor for 5alpha-dihydrotestosterone from Streptomyces hydrogenans. Streptomyces hydrogenans exhibits binding activity for 5alpha-dihydrotestosterone (17 beta-hydroxy-5alpha-androstan-3-one) in vivo. A cell free homogenate from the microorganism binds 5alpha-dihydrotestosterone in vitro as well. The association constant is 10(8) M-1 at 4 degrees C. Progesterone, but neither testerone nor cyproterone, competes with 5alpha-dihydrotestosterone for binding. The binding fraction from Streptomyces hydrogenans permits a simple assay for 5 alpha-dihydrotestosterone in biological samples."} {"id": "PMID:175620", "title": "[An experimental study of mixed tularemia and Omsk hemorrhagic fever infection in muskrats].", "content": "Musk-rats were infected simultaneously and at three-day interval with tularemia and Omsk hemorrhagic fever (OHF); the course of this mixed infection under the mentioned conditions were studied. Virological, microbiological and morphological data indicated that infection of musk-rats with OHF and tularemia caused development of mixed infection in them. A more severe course of mixed infection was associated with enhanced vascular affections caused by the action of the OHF virus. An inhibition of tularemia caused by the OHF development was noted in the course of mixed infection.", "contents": "[An experimental study of mixed tularemia and Omsk hemorrhagic fever infection in muskrats]. Musk-rats were infected simultaneously and at three-day interval with tularemia and Omsk hemorrhagic fever (OHF); the course of this mixed infection under the mentioned conditions were studied. Virological, microbiological and morphological data indicated that infection of musk-rats with OHF and tularemia caused development of mixed infection in them. A more severe course of mixed infection was associated with enhanced vascular affections caused by the action of the OHF virus. An inhibition of tularemia caused by the OHF development was noted in the course of mixed infection."} {"id": "PMID:175621", "title": "Glucocorticoid therapy for acute myocardial infarction.", "content": "Several uncontrolled early studies established that corticosteroid administration to patients with ischemic heart disease and cardiogenic shock was relatively safe. Whether or not the glucocorticoids were of benefit or not remained unclear when mortality was used as an index of efficacy. Hemodynamically, glucocorticoids may decrease peripheral vascular resistance, increase cardiac output and coronary blood flow, but leave myocardial contractility unchanged. The mean arterial pressure may vary unpredictably. The increase in coronary blood flow may certainly be advantageous in treating patients with acute myocardial infarction. The decrease in infarct size recently reported, if confirmed in man, would also be desirable. However, there is a paucity of good data concerning the effects of corticosteroids in man postinfarction. In addition, through unproved mechanisms, the corticosteroids decrease the extent and severity of myocardial ischemic injury. While these fundamental actions may not result in improved mortality, ongoing studies suggest that minimization of ischemic injury may ultimately prove to be most rewarding in the prevention of cardiogenic shock.", "contents": "Glucocorticoid therapy for acute myocardial infarction. Several uncontrolled early studies established that corticosteroid administration to patients with ischemic heart disease and cardiogenic shock was relatively safe. Whether or not the glucocorticoids were of benefit or not remained unclear when mortality was used as an index of efficacy. Hemodynamically, glucocorticoids may decrease peripheral vascular resistance, increase cardiac output and coronary blood flow, but leave myocardial contractility unchanged. The mean arterial pressure may vary unpredictably. The increase in coronary blood flow may certainly be advantageous in treating patients with acute myocardial infarction. The decrease in infarct size recently reported, if confirmed in man, would also be desirable. However, there is a paucity of good data concerning the effects of corticosteroids in man postinfarction. In addition, through unproved mechanisms, the corticosteroids decrease the extent and severity of myocardial ischemic injury. While these fundamental actions may not result in improved mortality, ongoing studies suggest that minimization of ischemic injury may ultimately prove to be most rewarding in the prevention of cardiogenic shock."} {"id": "PMID:175622", "title": "Stimulatory effect of FSH in vitro on the extracellularly active cyclic AMP phosphodiesterase in the prepubertal rat ovary.", "content": "Intact prepubertal rat ovaries were incubated with radioactively labelled adenosine 3',5'-cyclic monophosphate (cAMP) in Krebs bicarbonate buffer containing glucose. The rate of degradation of cAMP was determined by measuring the radioactivity in the medium after precipitation with Ba(OH)2 and ZnSO4. The fate of the nucleotide was followed by measuring the products in the incubation medium. Paper chromatography was used for the separation and identification of these products. It was found that cAMP was degraded to AMP, which in turn was degraded to inorganic phosphate (Pi) and adenosine. An uptake of labelled products was also observed. NIH-FSH-S9 (10 and 100 mug/ml), but not NIH-LH-B8 (0.1-100 mug/ml), increased the degradation of cAMP. Concomitantly, an increased accumulation of labelled adenosine and Pi as well as an increased uptake of labelled products were seen. Kinetic studies with low concentrations of cAMP (0.125-0.025 mumol/l) revealed an apparent Km value of 0.12 mumol/l for the phosphodiesterase (PDE) activity. FSH significantly changed the slope of the curve in the Lineweaver-Burk plot by increasing the PDE activity. The increased PDE activity in the presence of FSH is discussed in relation to earlier findings of differences in action betweeh LH and FSH on the cAMP system in the prepubertal rat ovary.", "contents": "Stimulatory effect of FSH in vitro on the extracellularly active cyclic AMP phosphodiesterase in the prepubertal rat ovary. Intact prepubertal rat ovaries were incubated with radioactively labelled adenosine 3',5'-cyclic monophosphate (cAMP) in Krebs bicarbonate buffer containing glucose. The rate of degradation of cAMP was determined by measuring the radioactivity in the medium after precipitation with Ba(OH)2 and ZnSO4. The fate of the nucleotide was followed by measuring the products in the incubation medium. Paper chromatography was used for the separation and identification of these products. It was found that cAMP was degraded to AMP, which in turn was degraded to inorganic phosphate (Pi) and adenosine. An uptake of labelled products was also observed. NIH-FSH-S9 (10 and 100 mug/ml), but not NIH-LH-B8 (0.1-100 mug/ml), increased the degradation of cAMP. Concomitantly, an increased accumulation of labelled adenosine and Pi as well as an increased uptake of labelled products were seen. Kinetic studies with low concentrations of cAMP (0.125-0.025 mumol/l) revealed an apparent Km value of 0.12 mumol/l for the phosphodiesterase (PDE) activity. FSH significantly changed the slope of the curve in the Lineweaver-Burk plot by increasing the PDE activity. The increased PDE activity in the presence of FSH is discussed in relation to earlier findings of differences in action betweeh LH and FSH on the cAMP system in the prepubertal rat ovary."} {"id": "PMID:175619", "title": "[The effect of arecoline on the structure of sleep and wakefulness in hens].", "content": "In chronic experiments on hens, studies have been made on the role of cholinergic mechanisms in regulation of the cycles \"awakefulness-sleep\". A cholinomimetic, arecoline, was used which stimulates M-cholinoreceptive brain neurons. Arecoline was injected intramuscularly in a dose 0.2 mg/kg of body weight. It was shown that cholinergic mechanisms are involved into the formation of \"awakefulness-sleep\" cycles in hens. Activation of these mechanisms facilitates paradoxical stage of sleep and expecially such its components as rapid eye movements, the decrease of tonus in neck muscles and, presumably, ponto-geniculo-occipital discharge. Arecolin affects not only the structure of paradoxical sleep, but both the awakefulness and mechanisms of slow-wave sleep stage.", "contents": "[The effect of arecoline on the structure of sleep and wakefulness in hens]. In chronic experiments on hens, studies have been made on the role of cholinergic mechanisms in regulation of the cycles \"awakefulness-sleep\". A cholinomimetic, arecoline, was used which stimulates M-cholinoreceptive brain neurons. Arecoline was injected intramuscularly in a dose 0.2 mg/kg of body weight. It was shown that cholinergic mechanisms are involved into the formation of \"awakefulness-sleep\" cycles in hens. Activation of these mechanisms facilitates paradoxical stage of sleep and expecially such its components as rapid eye movements, the decrease of tonus in neck muscles and, presumably, ponto-geniculo-occipital discharge. Arecolin affects not only the structure of paradoxical sleep, but both the awakefulness and mechanisms of slow-wave sleep stage."} {"id": "PMID:175623", "title": "Polysaccharides, proteins, nucleic acids, enzymes and sulfate uptake of the gastric epithelial cells of Xenodon merremii Wagler, 1824 (Ophidia): an histochemical and autoradiographic study.", "content": "Several histochemical tests were applied to the lining and glandular gastric epithelium of Xenodon merremii. Our observations, after discussion and interpretation, conducted to the following conclusions: 1. the surface epithelial cells, the neck cells, the body cells and the pyloric cells showed neutral polysaccharides, arginine, tyrosine, cysteine, acid phosphatase, AMPase and esterase. 2. besides these substances, in the surface epithelial cells was found tryptophan and in the body cells tryptophan and RNA.", "contents": "Polysaccharides, proteins, nucleic acids, enzymes and sulfate uptake of the gastric epithelial cells of Xenodon merremii Wagler, 1824 (Ophidia): an histochemical and autoradiographic study. Several histochemical tests were applied to the lining and glandular gastric epithelium of Xenodon merremii. Our observations, after discussion and interpretation, conducted to the following conclusions: 1. the surface epithelial cells, the neck cells, the body cells and the pyloric cells showed neutral polysaccharides, arginine, tyrosine, cysteine, acid phosphatase, AMPase and esterase. 2. besides these substances, in the surface epithelial cells was found tryptophan and in the body cells tryptophan and RNA."} {"id": "PMID:175618", "title": "[Functional topography of somatic muscles in euciscus idus].", "content": "The intensity of tissue respiration and anaerobic glycolysis, as well as the activity of succinic oxidase, cytochrome oxidase, lactate dehydrogenase and ATPase in skeletal muscles of the ide L. idus significantly increase from head to tail. Cranio-caudal gradients of the intensity of tissue respiration and the enzymic activity are especially evident in the red muscle, namely m. lateralis superficialis. In white m. lateralis magnus, the gradient of glycolytic activity is most pronounced. Biochemical and morphological peculiarities of muscles are discussed in relation to functional profile of the latter.", "contents": "[Functional topography of somatic muscles in euciscus idus]. The intensity of tissue respiration and anaerobic glycolysis, as well as the activity of succinic oxidase, cytochrome oxidase, lactate dehydrogenase and ATPase in skeletal muscles of the ide L. idus significantly increase from head to tail. Cranio-caudal gradients of the intensity of tissue respiration and the enzymic activity are especially evident in the red muscle, namely m. lateralis superficialis. In white m. lateralis magnus, the gradient of glycolytic activity is most pronounced. Biochemical and morphological peculiarities of muscles are discussed in relation to functional profile of the latter."} {"id": "PMID:175625", "title": "Histochemical localization of hydrolytic enzymes in the buffalo spermatozoa.", "content": "A histochemical study was made of the localization of alkaline and acid phosphatase, 5-nucleotidase and ATPase in the ejaculated buffalo spermatozoa. Most of these hydrolytic enzymes were localized in the mid-piece, and post-nuclear cap. Acid and alkaline phosphatase activities were also present in the acrosome. The presence of hydrolytic enzymes at these sites is discussed and correlated with the permeability and transport processes across the membranes of spermatozoa as well as with the process of energy production and fertilization.", "contents": "Histochemical localization of hydrolytic enzymes in the buffalo spermatozoa. A histochemical study was made of the localization of alkaline and acid phosphatase, 5-nucleotidase and ATPase in the ejaculated buffalo spermatozoa. Most of these hydrolytic enzymes were localized in the mid-piece, and post-nuclear cap. Acid and alkaline phosphatase activities were also present in the acrosome. The presence of hydrolytic enzymes at these sites is discussed and correlated with the permeability and transport processes across the membranes of spermatozoa as well as with the process of energy production and fertilization."} {"id": "PMID:175626", "title": "Thyroid C-cells in normal and goitrous gland: a histochemical study.", "content": "16 cases of goiter were examined for C-cells and 4 cases with normal thyroid gland. C-cells identification was based on masked metachromasia. There was stated both in toxic, atoxic goitrous tissue two forms of C-cells. The first characterized by positive metachromatic reaction and weak argyrophinty, the second type of C-cells were orthochromatic and argyrophilic. Metachromatic C-cells characterized as a rule by high alpha glycero phosphate menadione reductase as well succinic dehydrogenase and cytochrome oxidase.", "contents": "Thyroid C-cells in normal and goitrous gland: a histochemical study. 16 cases of goiter were examined for C-cells and 4 cases with normal thyroid gland. C-cells identification was based on masked metachromasia. There was stated both in toxic, atoxic goitrous tissue two forms of C-cells. The first characterized by positive metachromatic reaction and weak argyrophinty, the second type of C-cells were orthochromatic and argyrophilic. Metachromatic C-cells characterized as a rule by high alpha glycero phosphate menadione reductase as well succinic dehydrogenase and cytochrome oxidase."} {"id": "PMID:175627", "title": "Intracranial hemangiopericytoma: ultrastructural evidence of its leiomyoblastic differentiation.", "content": "Two intracranial hemangiopericytomas revealed subcellular features of the neoplastic elements comparable to those observed in normal and neoplastic smooth muscle. These included intracytoplasmic and submembranous fusiform dense bodies associated with bundles of filaments, tapered configuration of cells with grouping of cytoplasmic organelles at nuclear poles and deposition of intercellular basal lamina-like material. These observations are consistent with the pericytic origin but opposed to the ofttimes postulated meningothelial derivation of the neoplasm.", "contents": "Intracranial hemangiopericytoma: ultrastructural evidence of its leiomyoblastic differentiation. Two intracranial hemangiopericytomas revealed subcellular features of the neoplastic elements comparable to those observed in normal and neoplastic smooth muscle. These included intracytoplasmic and submembranous fusiform dense bodies associated with bundles of filaments, tapered configuration of cells with grouping of cytoplasmic organelles at nuclear poles and deposition of intercellular basal lamina-like material. These observations are consistent with the pericytic origin but opposed to the ofttimes postulated meningothelial derivation of the neoplasm."} {"id": "PMID:175628", "title": "Some effects of intracerebral lead implantation in the rat.", "content": "Pellets of lead acetate were implanted into the forebrains of adult rats which were sacrificed at intervals between 4 days and 4 weeks thereafter. Parenchymal necrosis and a number of reactive changes including edema and macrophage invasion were observed. Lead deposits were found in the extracellular spaces and within macrophages but only to a slight extent within glial or meningeal cells. Vascular changes were quite remarkable and included proliferation and the appearance of fenestrated blood vessels as well as some with tubular bodies and striking increases in the number of pinocytotic vesicles.", "contents": "Some effects of intracerebral lead implantation in the rat. Pellets of lead acetate were implanted into the forebrains of adult rats which were sacrificed at intervals between 4 days and 4 weeks thereafter. Parenchymal necrosis and a number of reactive changes including edema and macrophage invasion were observed. Lead deposits were found in the extracellular spaces and within macrophages but only to a slight extent within glial or meningeal cells. Vascular changes were quite remarkable and included proliferation and the appearance of fenestrated blood vessels as well as some with tubular bodies and striking increases in the number of pinocytotic vesicles."} {"id": "PMID:175629", "title": "Differential morphological reaction of experimental CNS tumour clones in vitro to dibutyryl cyclic AMP or serum-free medium, resp.", "content": "Six clones from methylnitrosourea (MNU) or ethylnitrosourea (ENU) induced tumours obtained in the nervous system of the rat were cultured in serum-free medium or treated with dibutyryl cyclic AMP (db cAMP) in vitro. All clones originated from longterm cultures. Three clones forming sarcomas after syngeneic transplantation showed only very slight changes following treatment, whereas the three glioma clones showed striking alterations. They formed long processes or showed rounding of their perikarya. In serum-free medium the cellular shape is intermediate between that seen in normal conditions and the seen in db cAMP treated cultures. The altered cultures resemble the primary cultures of the respective tumours. The relationship of these alterations to tumour types are discussed.", "contents": "Differential morphological reaction of experimental CNS tumour clones in vitro to dibutyryl cyclic AMP or serum-free medium, resp. Six clones from methylnitrosourea (MNU) or ethylnitrosourea (ENU) induced tumours obtained in the nervous system of the rat were cultured in serum-free medium or treated with dibutyryl cyclic AMP (db cAMP) in vitro. All clones originated from longterm cultures. Three clones forming sarcomas after syngeneic transplantation showed only very slight changes following treatment, whereas the three glioma clones showed striking alterations. They formed long processes or showed rounding of their perikarya. In serum-free medium the cellular shape is intermediate between that seen in normal conditions and the seen in db cAMP treated cultures. The altered cultures resemble the primary cultures of the respective tumours. The relationship of these alterations to tumour types are discussed."} {"id": "PMID:175631", "title": "Chemotherapeutic effects of some alkylating derivatives of nitrosourea on the development of tumors transplacentally induced in rats by ENU.", "content": "The application of BCNU, CCNU and MeCCNU has been shown to greatly reduce the number of tumors induced in rats by transplacentally administered ENU and to inhibit the full development of tumor proliferation. Moreover, no neurinomas appeared after treatment with CCNU. The application of GCNU proved to be much less effective. Our statistics in the form of tables showing these findings are included and discussed.", "contents": "Chemotherapeutic effects of some alkylating derivatives of nitrosourea on the development of tumors transplacentally induced in rats by ENU. The application of BCNU, CCNU and MeCCNU has been shown to greatly reduce the number of tumors induced in rats by transplacentally administered ENU and to inhibit the full development of tumor proliferation. Moreover, no neurinomas appeared after treatment with CCNU. The application of GCNU proved to be much less effective. Our statistics in the form of tables showing these findings are included and discussed."} {"id": "PMID:175632", "title": "Mononucleosis-associated subacute sclerosing panencephalitis.", "content": "A thirteen-year-old girl died of subacute sclerosing panencephalitis (SSPE) which occurred as part of a complex encephalitic illness related to acute infectious mononucleosis. The cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) fluorescent antibody (FA) titer was 1:64. Electron microscopic examination revealed 17 nanometer (nm) diameter paramyxovirus-like nucleocapsids in brain sections and 90 nm diameter herpes virus-like enveloped particles in negatively stained brain tissue extracts. Indirect FA staining of cerebral cortex sections demonstrated both measles and EBV antigenic material. EBV antigenic material has not previously been demonstrated in brain tissue. The proportion of B lymphocytes among the patient's peripheral blood lymphocytes was significantly increased as compared to normal controls, while the T lymphocyte percentage was normal. It is suggested that defects in cellular immunity associated with infectious mononucleosis may have been responsible for activation of latent measles-like virus. This is the tenth reported case in which two viruses have been associated with SSPE. This is the third instance in the authors' experience in which acute EBV infection has occurred coincident with the development of SSPE.", "contents": "Mononucleosis-associated subacute sclerosing panencephalitis. A thirteen-year-old girl died of subacute sclerosing panencephalitis (SSPE) which occurred as part of a complex encephalitic illness related to acute infectious mononucleosis. The cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) fluorescent antibody (FA) titer was 1:64. Electron microscopic examination revealed 17 nanometer (nm) diameter paramyxovirus-like nucleocapsids in brain sections and 90 nm diameter herpes virus-like enveloped particles in negatively stained brain tissue extracts. Indirect FA staining of cerebral cortex sections demonstrated both measles and EBV antigenic material. EBV antigenic material has not previously been demonstrated in brain tissue. The proportion of B lymphocytes among the patient's peripheral blood lymphocytes was significantly increased as compared to normal controls, while the T lymphocyte percentage was normal. It is suggested that defects in cellular immunity associated with infectious mononucleosis may have been responsible for activation of latent measles-like virus. This is the tenth reported case in which two viruses have been associated with SSPE. This is the third instance in the authors' experience in which acute EBV infection has occurred coincident with the development of SSPE."} {"id": "PMID:175633", "title": "[Niemann-Pick disease (Crocker's type C): ultrastructural study of a case (author's transl)].", "content": "The authors report electron microscopic findings in brain, bone marrow and liver biopsies in a case of juvenile Niemann-Pick disease (Crocker's type C). The diagnosis was supported by clinical data increase of blood sphingomyelin and vacuolated histiocytes in bone marrow and liver. Neurons and glial cells were filled with two types of cytosomes: classical multilamellar bodies and unusual pleiomorphic bodies. The latter type probably showed some lipofuscinic component. The relationship between type C and classical Niemann-Pick disease is discussed.", "contents": "[Niemann-Pick disease (Crocker's type C): ultrastructural study of a case (author's transl)]. The authors report electron microscopic findings in brain, bone marrow and liver biopsies in a case of juvenile Niemann-Pick disease (Crocker's type C). The diagnosis was supported by clinical data increase of blood sphingomyelin and vacuolated histiocytes in bone marrow and liver. Neurons and glial cells were filled with two types of cytosomes: classical multilamellar bodies and unusual pleiomorphic bodies. The latter type probably showed some lipofuscinic component. The relationship between type C and classical Niemann-Pick disease is discussed."} {"id": "PMID:175634", "title": "Ultrastructure of the Gunn rat substantia nigra. II. Mitochondrial changes.", "content": "The substantia nigra of hyperbilirubinemic (Gunn) rats was studied using light and electron microscopic techniques. PAS-positive inclusions were observed within the neuronal somata of animals 2 to 12 weeks old. Incubation of tissue sections in 0.5% diastase inhibited most of the positive PAS reaction, thus indicating the intraneuronal presence of glycogen. Electron microscopic examination of the tissue substantiated the histochemical data. Mitochondria in neuronal somata contained collections of osmiophilic granules, 200-300 A diameter, in their intracristal (intermembrane) space. These granules were typical of beta-glycogen particles. In increasingly older animals (from 2 to 12 weeks old) progressively fewer collections of intramitochondrial glycogen were observed. In these same animals there was, however, a concomitant increase of osmiophilic granules, 400-600 A diameter, located in the cisternae of granular endoplasmic reticulum. These granules corresponded to alpha-glycogen. After 12 weeks of age, only occasional glycogen granules were seen in either the mitochondria or endoplasmic reticulum. It is suggested that the intramitochondrial glycogen represents an alternate means by which the neuron is able to manufacture ATP following the disruption of oxydative phosphorylation caused by bilirubin. Furthermore it is suggested that with the recovery of oxydative phosphorylation the intramitochondrial collections of glycogen are transferred to the endoplasmic reticulum where glycogenolysis might possibly occur.", "contents": "Ultrastructure of the Gunn rat substantia nigra. II. Mitochondrial changes. The substantia nigra of hyperbilirubinemic (Gunn) rats was studied using light and electron microscopic techniques. PAS-positive inclusions were observed within the neuronal somata of animals 2 to 12 weeks old. Incubation of tissue sections in 0.5% diastase inhibited most of the positive PAS reaction, thus indicating the intraneuronal presence of glycogen. Electron microscopic examination of the tissue substantiated the histochemical data. Mitochondria in neuronal somata contained collections of osmiophilic granules, 200-300 A diameter, in their intracristal (intermembrane) space. These granules were typical of beta-glycogen particles. In increasingly older animals (from 2 to 12 weeks old) progressively fewer collections of intramitochondrial glycogen were observed. In these same animals there was, however, a concomitant increase of osmiophilic granules, 400-600 A diameter, located in the cisternae of granular endoplasmic reticulum. These granules corresponded to alpha-glycogen. After 12 weeks of age, only occasional glycogen granules were seen in either the mitochondria or endoplasmic reticulum. It is suggested that the intramitochondrial glycogen represents an alternate means by which the neuron is able to manufacture ATP following the disruption of oxydative phosphorylation caused by bilirubin. Furthermore it is suggested that with the recovery of oxydative phosphorylation the intramitochondrial collections of glycogen are transferred to the endoplasmic reticulum where glycogenolysis might possibly occur."} {"id": "PMID:175636", "title": "Glycerokinase in brain and liver of low birth weight newborns.", "content": "Glycerokinase activity was measured in brain and liver tissue of decreased low birth weight newborns. No glycerokinase activity was found in the brain. In the liver a relatively high activity of glycerokinase was ascertained even in very immature newborns.", "contents": "Glycerokinase in brain and liver of low birth weight newborns. Glycerokinase activity was measured in brain and liver tissue of decreased low birth weight newborns. No glycerokinase activity was found in the brain. In the liver a relatively high activity of glycerokinase was ascertained even in very immature newborns."} {"id": "PMID:175637", "title": "Considerations on treatment of nephroblastoma. A study of 36 cases.", "content": "Thirty-six patients with nephroblastoma in Stages I, II and III treated at Radiumhemmet between 1966 and 1973, were analysed. The tumors were classified into three different histological types. All 10 patients in Stage III have developed metastases. All patients in Stages I and II (5 out of 26) who developed metastases had poorly differentiated (histological Type III) tumours. The indications for postoperative irradiation and chemotherapy for the different stages and histological types of the tumour are discussed.", "contents": "Considerations on treatment of nephroblastoma. A study of 36 cases. Thirty-six patients with nephroblastoma in Stages I, II and III treated at Radiumhemmet between 1966 and 1973, were analysed. The tumors were classified into three different histological types. All 10 patients in Stage III have developed metastases. All patients in Stages I and II (5 out of 26) who developed metastases had poorly differentiated (histological Type III) tumours. The indications for postoperative irradiation and chemotherapy for the different stages and histological types of the tumour are discussed."} {"id": "PMID:175638", "title": "Ulcer formation and histochemical changes in rat-stomach mucosa induced by acetylsalicylic acid.", "content": "Numerous papers have emphasized the damaging effect of salicylic acid compounds on the stomach mucosa. The investigations here reported aimed at examining the effect on gastric and duodenal morphology of a moderate dose of aspirin. Oxidative enzymes were evaluated histochemically. To rats in groups of 16, aspirin tablets, placebo tablets, or the same with additional 1 cc of 0.1 N HCl, were administered twice a day for 6 weeks. Approximately 160 mg/kg/24 hrs. were ingested. Microscopy revealed severe hyperaemia along with focal gastritis in the aspirin treated animals. Chronic gactric ulcers were observed in 18 rats in the aspirin treated groups, particularly in the group where HCl was added. Ulcerations in the area of the pyloricgland occurred in the latter group only. A reduction in mucopolysaccharides was demonstrated and involved the acid as well as the neutral ones. NADH-reductase and cytochrome oxidase were inhibited not only in the surface cells but also in those in the deeper layers. The reduction in oxidative enzymes in otherwise undamaged areas suggests an interference with the cellular metabolism, probably processes in the respiratory chain which might lead to reduction in energy-rich phosphate bonds.", "contents": "Ulcer formation and histochemical changes in rat-stomach mucosa induced by acetylsalicylic acid. Numerous papers have emphasized the damaging effect of salicylic acid compounds on the stomach mucosa. The investigations here reported aimed at examining the effect on gastric and duodenal morphology of a moderate dose of aspirin. Oxidative enzymes were evaluated histochemically. To rats in groups of 16, aspirin tablets, placebo tablets, or the same with additional 1 cc of 0.1 N HCl, were administered twice a day for 6 weeks. Approximately 160 mg/kg/24 hrs. were ingested. Microscopy revealed severe hyperaemia along with focal gastritis in the aspirin treated animals. Chronic gactric ulcers were observed in 18 rats in the aspirin treated groups, particularly in the group where HCl was added. Ulcerations in the area of the pyloricgland occurred in the latter group only. A reduction in mucopolysaccharides was demonstrated and involved the acid as well as the neutral ones. NADH-reductase and cytochrome oxidase were inhibited not only in the surface cells but also in those in the deeper layers. The reduction in oxidative enzymes in otherwise undamaged areas suggests an interference with the cellular metabolism, probably processes in the respiratory chain which might lead to reduction in energy-rich phosphate bonds."} {"id": "PMID:175639", "title": "Occurrence of reo-like calf viruses in young children with acute gastroenteritis. Diagnoses established by electron microscopy and complement fixation, using the reo-like virus as antigen.", "content": "In the course of a six-month-study of acute gastroenteritis in children of ages up to six years, a reo-like virus was found in 54 per cent of the faecal specimens obtained at an early stage of the disease, using electron microscopy as screening test. By means of a concentrated complement fixation antigen, composed of a related calf diarrhoea virus cultivated in tissue culture, the rise in titre was found to be significant in 96 per cent of the patients whose faeces contained the reo-like virus. Antibodies were present in the remaining 4 per cent without rise in titre. In 10 per cent of the cases with gastroenteritis infection was caused by adenovirus or Salmonella. A probable aetiological agent was found in 71 per cent of the patients. It applies to 33 per cent of all cases caused by the reo-like virus that they were nosocomial infections.", "contents": "Occurrence of reo-like calf viruses in young children with acute gastroenteritis. Diagnoses established by electron microscopy and complement fixation, using the reo-like virus as antigen. In the course of a six-month-study of acute gastroenteritis in children of ages up to six years, a reo-like virus was found in 54 per cent of the faecal specimens obtained at an early stage of the disease, using electron microscopy as screening test. By means of a concentrated complement fixation antigen, composed of a related calf diarrhoea virus cultivated in tissue culture, the rise in titre was found to be significant in 96 per cent of the patients whose faeces contained the reo-like virus. Antibodies were present in the remaining 4 per cent without rise in titre. In 10 per cent of the cases with gastroenteritis infection was caused by adenovirus or Salmonella. A probable aetiological agent was found in 71 per cent of the patients. It applies to 33 per cent of all cases caused by the reo-like virus that they were nosocomial infections."} {"id": "PMID:175640", "title": "Human ecto- and endocervical epithelial cells as targets for herpes simplex type two infection in vitro.", "content": "An in vitro method was used to compare the herpes simplex virus type 2 (HSV2) susceptibility of human ecto- and endocervical epithelial cells as well as the induced cellular alterations. HSV2 caused a productive infection and morphological alterations both in ecto- and endocervical epithelial cells, but the cytopathogenicity, virus production and development of HSV2 antigens showed a greater sensitivity of ectocervical cells to HSV2 infection. The cytopathogenicity and production of infectious virus did not depend on the antibody pattern of the target cell donor patients. Basically similar morphological alterations were seen in ecto- and endocervical cultures and the various morphological types of altered cells are described.", "contents": "Human ecto- and endocervical epithelial cells as targets for herpes simplex type two infection in vitro. An in vitro method was used to compare the herpes simplex virus type 2 (HSV2) susceptibility of human ecto- and endocervical epithelial cells as well as the induced cellular alterations. HSV2 caused a productive infection and morphological alterations both in ecto- and endocervical epithelial cells, but the cytopathogenicity, virus production and development of HSV2 antigens showed a greater sensitivity of ectocervical cells to HSV2 infection. The cytopathogenicity and production of infectious virus did not depend on the antibody pattern of the target cell donor patients. Basically similar morphological alterations were seen in ecto- and endocervical cultures and the various morphological types of altered cells are described."} {"id": "PMID:175642", "title": "Adenosine 3',5'-cyclic monophosphate in perfused rat hearts exposed to isoprenaline and dopamine.", "content": "Isoprenaline and dopamine increased cyclic AMP (cAMP) content and contractile activity of isolated perfused rat hearts. The changes of cAMP levels depended on the mode of drug administration. Isoprenaline (4 x 10(-10) mol) administered to the perfused heart as a relatively concentrated bolus, caused a substantial, rapid and transient increase of cAMP. Isoprenaline (2 x 10(-10) mol and 4 x 10(-10) mol) and dopamine (10(-7) mol) diluted in 40 ml of perfusate which was continuously recirculated through the heart, caused a gradual increase of cAMP content which approached an apparent steady state. cAMP accumulation occurred at isoprenaline concentrations above 10(-9) M and at dopamine concentrations above 10(-6) M. Both agents also increased cAMP labelling from 14C-adenine in the perfusate, probably indicating increased cAMP synthesis. Isoprenaline at 2 x 10(-8) M and 10(-7) M increased labelling more than content of cAMP. Isoprenaline and dopamine also increased phosphorylase a activity. An association between increased cAMP contents and increased contractile activity was revealed by both the time-response and the dose-response curves of hearts exposed to isoprenaline and dopamine. Since both agents stimulate adrenergic beta-receptors in cardiac muscle, the results are concordant with the hypothesis that cAMP is involved as a mediator of the inotropic response to adrenergic beta-stimulation.", "contents": "Adenosine 3',5'-cyclic monophosphate in perfused rat hearts exposed to isoprenaline and dopamine. Isoprenaline and dopamine increased cyclic AMP (cAMP) content and contractile activity of isolated perfused rat hearts. The changes of cAMP levels depended on the mode of drug administration. Isoprenaline (4 x 10(-10) mol) administered to the perfused heart as a relatively concentrated bolus, caused a substantial, rapid and transient increase of cAMP. Isoprenaline (2 x 10(-10) mol and 4 x 10(-10) mol) and dopamine (10(-7) mol) diluted in 40 ml of perfusate which was continuously recirculated through the heart, caused a gradual increase of cAMP content which approached an apparent steady state. cAMP accumulation occurred at isoprenaline concentrations above 10(-9) M and at dopamine concentrations above 10(-6) M. Both agents also increased cAMP labelling from 14C-adenine in the perfusate, probably indicating increased cAMP synthesis. Isoprenaline at 2 x 10(-8) M and 10(-7) M increased labelling more than content of cAMP. Isoprenaline and dopamine also increased phosphorylase a activity. An association between increased cAMP contents and increased contractile activity was revealed by both the time-response and the dose-response curves of hearts exposed to isoprenaline and dopamine. Since both agents stimulate adrenergic beta-receptors in cardiac muscle, the results are concordant with the hypothesis that cAMP is involved as a mediator of the inotropic response to adrenergic beta-stimulation."} {"id": "PMID:175651", "title": "Toxicity and metabolism of methyl n-butyl ketone.", "content": "MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.", "contents": "Toxicity and metabolism of methyl n-butyl ketone. MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione."} {"id": "PMID:175652", "title": "Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer.", "content": "Six cases of primary lung cancer that closely mimic malignant pleural mesothelioma clinically and anatomically are compared with four proven cases of malignant pleural mesothelioma. Findings on roentgenograms of the chest, clinical history, and gross examination of the lung specimens are not helpful in distinguishing between these two neoplasms. Microscopic examination of the hematoxylin and eosin-stained tissues is often inconclusive. Tissues were stained with hematoxylin and eosin, PAS with and without diastase treatment (DPAS), mucicarmine, alcian blue, toluidine blue, and colloidal iron with and without digestion by testicular hyaluronidase. Among these histochemical methods, DPAS was found to be particularly useful in distinguishing the primary lung cancers from the mesotheliomas. All primary lung cancers except one showed DPAS-positive material (mucin) in both the cytoplasm of the cancer cells and within the lumina of neoplastic glands. In contrast, none of the mesotheliomas showed the presence of DPAS-positive material. Histologically, all lung cancers were glandular. Five were classified as bronchiolar carcinoma, the remaining one as poorly differentiated adenocarcinoma. In two of the bronchiolar carcinomas, a small subpleural primary focus was demonstrated. This finding suggests a possible origin of these cancers as a small subpleural tumor that became widely disseminated via the subpleural lymphatics. This form of primary lung cancer possesses sufficient gross and microscopic characteristics that recognition should be given to it as a variant of primary lung cancer, with emphasis on differentiating it from pleural mesothelioma.", "contents": "Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer. Six cases of primary lung cancer that closely mimic malignant pleural mesothelioma clinically and anatomically are compared with four proven cases of malignant pleural mesothelioma. Findings on roentgenograms of the chest, clinical history, and gross examination of the lung specimens are not helpful in distinguishing between these two neoplasms. Microscopic examination of the hematoxylin and eosin-stained tissues is often inconclusive. Tissues were stained with hematoxylin and eosin, PAS with and without diastase treatment (DPAS), mucicarmine, alcian blue, toluidine blue, and colloidal iron with and without digestion by testicular hyaluronidase. Among these histochemical methods, DPAS was found to be particularly useful in distinguishing the primary lung cancers from the mesotheliomas. All primary lung cancers except one showed DPAS-positive material (mucin) in both the cytoplasm of the cancer cells and within the lumina of neoplastic glands. In contrast, none of the mesotheliomas showed the presence of DPAS-positive material. Histologically, all lung cancers were glandular. Five were classified as bronchiolar carcinoma, the remaining one as poorly differentiated adenocarcinoma. In two of the bronchiolar carcinomas, a small subpleural primary focus was demonstrated. This finding suggests a possible origin of these cancers as a small subpleural tumor that became widely disseminated via the subpleural lymphatics. This form of primary lung cancer possesses sufficient gross and microscopic characteristics that recognition should be given to it as a variant of primary lung cancer, with emphasis on differentiating it from pleural mesothelioma."} {"id": "PMID:175653", "title": "Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients.", "content": "We have studied insulin binding to circulating mononuclear cells obtained from 31 untreated, adult, nonobese, nonketotic diabetic subjects with fasting hyperglycemia, 40 normal subjects and four patients with fasting hyperglycemia secondary to chronic pancreatitis. Our results show that the mononuclear cells of untreated adult diabetic patients have a decreased ability to bind insulin when they are compared to cells obtained from normal subjects. The binding affinity for insulin was the same for both groups of cells, and the decreased binding could be accounted for by a 45 per cent decrease in the number of available insulin receptor sites per cell. Treatment with chlorpropamide (one to three months, average dose equals 375 mg/day) was associated with a marked reduction in hyperglycemia and an increase toward normal in insulin binding to mononuclear cells. In conclusion, (1) mononuclear cells from nonobese, nonketotic, untreated adult diabetic patients with fasting hyperglycemia demonstrate a decreased ability to bind insulin due to decreased numbers of insulin receptors per cell; (2) treatment with an oral hypoglycemic agent is associated with a diminution in hyperglycemia and a return toward normal of insulin binding.", "contents": "Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients. We have studied insulin binding to circulating mononuclear cells obtained from 31 untreated, adult, nonobese, nonketotic diabetic subjects with fasting hyperglycemia, 40 normal subjects and four patients with fasting hyperglycemia secondary to chronic pancreatitis. Our results show that the mononuclear cells of untreated adult diabetic patients have a decreased ability to bind insulin when they are compared to cells obtained from normal subjects. The binding affinity for insulin was the same for both groups of cells, and the decreased binding could be accounted for by a 45 per cent decrease in the number of available insulin receptor sites per cell. Treatment with chlorpropamide (one to three months, average dose equals 375 mg/day) was associated with a marked reduction in hyperglycemia and an increase toward normal in insulin binding to mononuclear cells. In conclusion, (1) mononuclear cells from nonobese, nonketotic, untreated adult diabetic patients with fasting hyperglycemia demonstrate a decreased ability to bind insulin due to decreased numbers of insulin receptors per cell; (2) treatment with an oral hypoglycemic agent is associated with a diminution in hyperglycemia and a return toward normal of insulin binding."} {"id": "PMID:175655", "title": "Circulating immune complexes and complement sequence activation in infectious mononucleosis.", "content": "The role of immune complex formation was investigated in a patient with infectious mononucleosis complicated by an urticarial rash. Circulating cryoprotein immune complexes were identified during the urticarial phase of the illness, and disappeared during recovery. These complexes were composed of immunoglobulins G (IgG), M (IgM) and A (IgA), complement components C3, C4 and C5, Epstein-Barr (EB) virus capsid antibody and particles resembling EB virus. The IgG subtypes identified in the immune complexes were the complement fixing IgG-1, IgG-2 and IgG-3. The C3 activator of the properdin complex was detected in serum obtained during that acute phase but not after recovery. Thus, the transient appearance of circulating complement-fixing immune complexes was associated in this patient with activation of both classic and alternate complement pathways. The findings suggest that these complexes may be involved in the rash associated with infectious mononucleosis.", "contents": "Circulating immune complexes and complement sequence activation in infectious mononucleosis. The role of immune complex formation was investigated in a patient with infectious mononucleosis complicated by an urticarial rash. Circulating cryoprotein immune complexes were identified during the urticarial phase of the illness, and disappeared during recovery. These complexes were composed of immunoglobulins G (IgG), M (IgM) and A (IgA), complement components C3, C4 and C5, Epstein-Barr (EB) virus capsid antibody and particles resembling EB virus. The IgG subtypes identified in the immune complexes were the complement fixing IgG-1, IgG-2 and IgG-3. The C3 activator of the properdin complex was detected in serum obtained during that acute phase but not after recovery. Thus, the transient appearance of circulating complement-fixing immune complexes was associated in this patient with activation of both classic and alternate complement pathways. The findings suggest that these complexes may be involved in the rash associated with infectious mononucleosis."} {"id": "PMID:175657", "title": "Effects of fasting and theophylline on alanine-stimulated glucagon secretion in neonatal and infant sheep.", "content": "Plasma concentrations of glucose, alanine, and glucagon were measured after 24 hour fasting in newborn and infant sheep and in response to infusion of alanine alone and concurrently with theophylline. The plasma glucagon response to alanine was minimal in newborn sheep; in contrast, alanine produced a brisk response in plasma glucagon concentration in infant sheep. Glucose concentrations were unchanged in both groups. Theophylline enhanced blood glucagon and glucose responses to alanine in newborn animals but had minimal effects on the response of the infant sheep. These data, considered with earlier data in fetal sheep, suggest a progressive maturation of pancreatic islet alpha-cell glucagon secretion in the sheep during the postnatal period and suggest that the blunted glucagon response observed in the neonate is related to immaturity of the glucagon secretion mechanisms rather than deficient synthesis of the hormone. This immaturity may be related to impaired synthesis and/or enhanced degradation of cyclic adenosine monophosphate (cAMP) or to diminished responsiveness to cAMP.", "contents": "Effects of fasting and theophylline on alanine-stimulated glucagon secretion in neonatal and infant sheep. Plasma concentrations of glucose, alanine, and glucagon were measured after 24 hour fasting in newborn and infant sheep and in response to infusion of alanine alone and concurrently with theophylline. The plasma glucagon response to alanine was minimal in newborn sheep; in contrast, alanine produced a brisk response in plasma glucagon concentration in infant sheep. Glucose concentrations were unchanged in both groups. Theophylline enhanced blood glucagon and glucose responses to alanine in newborn animals but had minimal effects on the response of the infant sheep. These data, considered with earlier data in fetal sheep, suggest a progressive maturation of pancreatic islet alpha-cell glucagon secretion in the sheep during the postnatal period and suggest that the blunted glucagon response observed in the neonate is related to immaturity of the glucagon secretion mechanisms rather than deficient synthesis of the hormone. This immaturity may be related to impaired synthesis and/or enhanced degradation of cyclic adenosine monophosphate (cAMP) or to diminished responsiveness to cAMP."} {"id": "PMID:175658", "title": "Trachoma in a rural Haitian community.", "content": "We selected 43 patients, aged 15 days to 57 yesrs, for intensive study after screening 975 people for clinical evidence of trachoma in rural Haiti. Trachoma was present in Haiti with low endemicity and was followed by relatively mild sequelae. Laboratory studies confirmed the disease through demonstration of conjunctival inclusion bodies by immunofluoresence and serotyping of antibody in sera or eye secretions, or both. Of 23 patients (age 1 to 36 years) with active trachoma, all had serum antibody to chlamydia (range 1:10 to 1:640), nine had eye secretion antibody (range 1:10 to 1:1280), and one was inclusion positive. The remaining 20 patients (age 15 days to 57 years) had the following diagnosis: atypical follicles (eight), conjunctivitis with or without mucopurulent discharge (ten) innactive pannus only (one), and severe anemia (one). Only 16 of the 20 were tested for serum antibody and all were positive (1:10 to 1:5,120), 11 of 20 had eye secretion antibody (1:10 to less than or equal to 1:640), and one was inclusion positive. Serotyping attempted on 22 patients yielded 16 patients with antibodies specific for type A, one patient with type B, and five who were not typed.", "contents": "Trachoma in a rural Haitian community. We selected 43 patients, aged 15 days to 57 yesrs, for intensive study after screening 975 people for clinical evidence of trachoma in rural Haiti. Trachoma was present in Haiti with low endemicity and was followed by relatively mild sequelae. Laboratory studies confirmed the disease through demonstration of conjunctival inclusion bodies by immunofluoresence and serotyping of antibody in sera or eye secretions, or both. Of 23 patients (age 1 to 36 years) with active trachoma, all had serum antibody to chlamydia (range 1:10 to 1:640), nine had eye secretion antibody (range 1:10 to 1:1280), and one was inclusion positive. The remaining 20 patients (age 15 days to 57 years) had the following diagnosis: atypical follicles (eight), conjunctivitis with or without mucopurulent discharge (ten) innactive pannus only (one), and severe anemia (one). Only 16 of the 20 were tested for serum antibody and all were positive (1:10 to 1:5,120), 11 of 20 had eye secretion antibody (1:10 to less than or equal to 1:640), and one was inclusion positive. Serotyping attempted on 22 patients yielded 16 patients with antibodies specific for type A, one patient with type B, and five who were not typed."} {"id": "PMID:175659", "title": "Clinical and laboratory evaluation of epidemic keratoconjunctivitis due to adenovirus types 8 and 19.", "content": "During a community outbreak of epidemic keratoconjunctivitis due to adenovirus types 8 and 19, we compared the clinical and laboratory characteristics of the two viruses. Much of the disease was mild and the keratoconjunctivitis associated with adenovirus type 8 was indistinguishable clinically from that associated with adenovirus type 19. Adenovirus type 8 was isolated only from the conjunctival sac, whereas adenovirus type 19 was frequently cultured from the nose, throat, and conjunctiva. The two adenovirus types were never isolated from the same individual. In a prospective study of ten individuals exposed to known cases, adenovirus type 19 was isolated from two without clinical disease.", "contents": "Clinical and laboratory evaluation of epidemic keratoconjunctivitis due to adenovirus types 8 and 19. During a community outbreak of epidemic keratoconjunctivitis due to adenovirus types 8 and 19, we compared the clinical and laboratory characteristics of the two viruses. Much of the disease was mild and the keratoconjunctivitis associated with adenovirus type 8 was indistinguishable clinically from that associated with adenovirus type 19. Adenovirus type 8 was isolated only from the conjunctival sac, whereas adenovirus type 19 was frequently cultured from the nose, throat, and conjunctiva. The two adenovirus types were never isolated from the same individual. In a prospective study of ten individuals exposed to known cases, adenovirus type 19 was isolated from two without clinical disease."} {"id": "PMID:175660", "title": "Pathogenesis of bronchopulmonary dysplasia following hyaline membrane disease.", "content": "The pathologic changes in the lungs of 112 infants dying from hyaline membrane disease (HMD) and 64 infants dying from other causes in the years 1967 to 1972 have been reviewed in order to obtain information about the pathogenesis of bronchopulmonary dysplasia (BPD). The results from the infants with HMD showed that: a) From the fourth or fifth day, the surface tension of lung extracts fell, inclusion bodies became more plentiful, and air saccules with patent airways could be inflated with air, even when severe changes due to BPD were present. b) There was a highly statistically significant correlation between the most serious lesions of BPD--damage to airways followed by excessive repair and fibrosis--and the use of high (greater than 35 cm H2O) peak airway pressures during mechanical ventilation in life. c) Damage due to oxygen breathing could not be reliably identified although some of the lesions, particularly edema and fibroplasia in intersaccular septa, may have been caused by oxygen. d) Evidence of pulmonary hypertension was present in infants surviving for more than a month with severe lung damage, and the ductus arteriosus was always open. We conclude that the most important factor in the pathogenesis of BPD following HMD is mechanical trauma to the lung from the use of excessively high peak airway pressures during mechanical ventilation.", "contents": "Pathogenesis of bronchopulmonary dysplasia following hyaline membrane disease. The pathologic changes in the lungs of 112 infants dying from hyaline membrane disease (HMD) and 64 infants dying from other causes in the years 1967 to 1972 have been reviewed in order to obtain information about the pathogenesis of bronchopulmonary dysplasia (BPD). The results from the infants with HMD showed that: a) From the fourth or fifth day, the surface tension of lung extracts fell, inclusion bodies became more plentiful, and air saccules with patent airways could be inflated with air, even when severe changes due to BPD were present. b) There was a highly statistically significant correlation between the most serious lesions of BPD--damage to airways followed by excessive repair and fibrosis--and the use of high (greater than 35 cm H2O) peak airway pressures during mechanical ventilation in life. c) Damage due to oxygen breathing could not be reliably identified although some of the lesions, particularly edema and fibroplasia in intersaccular septa, may have been caused by oxygen. d) Evidence of pulmonary hypertension was present in infants surviving for more than a month with severe lung damage, and the ductus arteriosus was always open. We conclude that the most important factor in the pathogenesis of BPD following HMD is mechanical trauma to the lung from the use of excessively high peak airway pressures during mechanical ventilation."} {"id": "PMID:175661", "title": "Immunopathogenicity and oncogenicity of murine leukemia viruses. II. Infection of mice and rats with Scripps leukemia virus.", "content": "The pathologic consequences of infection of newborn mice and rats with MuLV (Scripps leukemia virus--SLV) were observed. Serum MuLV p30 concentrations of most strains were elevated 20 to 100 times that of controls while MuLV gp70 levels were elevated only 1.1 to 14.8 times, probably reflecting in part the higher concentrations of gp70 in control sera but also indicating the lack of parallelism in regulation of synthesis of these two viral antigens. Infected mice of most strains developed immunologic diseases, including antinuclear antibody and glomerulonephritis, but not Coombs' antibodies. The nature and severity of the immunologic disease varied considerably, depending upon the genetic character of the host. Most infected animals developed lymphatic leukemias, but four strains showed partial to complete resistance to SLV oncogenesis: BALB/c (nude); C57 Bl/6; (NZB times NZW) F1, and (NZW times BALB/c) F1.", "contents": "Immunopathogenicity and oncogenicity of murine leukemia viruses. II. Infection of mice and rats with Scripps leukemia virus. The pathologic consequences of infection of newborn mice and rats with MuLV (Scripps leukemia virus--SLV) were observed. Serum MuLV p30 concentrations of most strains were elevated 20 to 100 times that of controls while MuLV gp70 levels were elevated only 1.1 to 14.8 times, probably reflecting in part the higher concentrations of gp70 in control sera but also indicating the lack of parallelism in regulation of synthesis of these two viral antigens. Infected mice of most strains developed immunologic diseases, including antinuclear antibody and glomerulonephritis, but not Coombs' antibodies. The nature and severity of the immunologic disease varied considerably, depending upon the genetic character of the host. Most infected animals developed lymphatic leukemias, but four strains showed partial to complete resistance to SLV oncogenesis: BALB/c (nude); C57 Bl/6; (NZB times NZW) F1, and (NZW times BALB/c) F1."} {"id": "PMID:175662", "title": "Synthesis of secretory component by colonic neoplasms.", "content": "The secretory component (SC) polypeptide chain of secretory immunoglobulin A can be considered as a differentiation marker in that it is normally synthesized in the non-mucus-containing columnar epithelial cells, but not goblet cells, of the large intestine. With this in mind, we have studied the expression of SC in 36 colonic adenocarcinomas and 15 polyps (adenomatous and villous) by the fluorescent antibody technique. As in the normal mucosa, the synthesis of SC in tumors found in non-mucus-containing columnar cells and was absent from goblet cells. However, in several well-differentiated carcinomas it appeared that columnar cells contained both SC and mucin; these cells could be analogous to the normal mucosal precursor of both cell types. SC was synthesized throughout all adenomatous polyps and villous adenomas with the exception of some atypical nonmucinous areas of adenomatous polyps. Secretory component synthesis by carcinomas was associated with mucus production, although goblet cells did not contain SC. The presence of SC also correlated with the degree of differentiation. Secretory component was absent from half of the carcinomas as well as from atypical nonmucinous areas of polyps, and this could represent one of the earliest changes associated with the development of malignancy.", "contents": "Synthesis of secretory component by colonic neoplasms. The secretory component (SC) polypeptide chain of secretory immunoglobulin A can be considered as a differentiation marker in that it is normally synthesized in the non-mucus-containing columnar epithelial cells, but not goblet cells, of the large intestine. With this in mind, we have studied the expression of SC in 36 colonic adenocarcinomas and 15 polyps (adenomatous and villous) by the fluorescent antibody technique. As in the normal mucosa, the synthesis of SC in tumors found in non-mucus-containing columnar cells and was absent from goblet cells. However, in several well-differentiated carcinomas it appeared that columnar cells contained both SC and mucin; these cells could be analogous to the normal mucosal precursor of both cell types. SC was synthesized throughout all adenomatous polyps and villous adenomas with the exception of some atypical nonmucinous areas of adenomatous polyps. Secretory component synthesis by carcinomas was associated with mucus production, although goblet cells did not contain SC. The presence of SC also correlated with the degree of differentiation. Secretory component was absent from half of the carcinomas as well as from atypical nonmucinous areas of polyps, and this could represent one of the earliest changes associated with the development of malignancy."} {"id": "PMID:175663", "title": "Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats.", "content": "In livers from fasted rats perfused with bicarbonate buffer containing bovine albumin and erythrocytes, adrenalectomy decreased glycogen levels and glucose production, impaired the incorporation of 14C from [14C]lactate into glucose or glycogen, and decreased the activity of the active (I) form of glycogen synthase. Cortisol treatment restored gluconeogenesis after 1 h and glycogen synthesis after 2 h. Adrenalectomy did not alter the production of glucose or lactate or the levels of gluconeogenic intermediates in livers from fasted rats perfused with fructose, but reduced the formation of glycogen from this substrate. Adrenalectomy increased the levels of lactate and decreased the levels of P-pyruvate and subsequent intermediates in the gluconeogenic pathway. These changes were reversed by cortisol treatment. It is concluded that glucocorticoids support gluconeogenesis and glycogen synthesis in livers from fasted rats primarily by facilitating a reaction(s) located between pyruvate and P-pyruvate in the gluconeogenic pathway and by promoting the conversion of inactive to active glycogen synthase.", "contents": "Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. In livers from fasted rats perfused with bicarbonate buffer containing bovine albumin and erythrocytes, adrenalectomy decreased glycogen levels and glucose production, impaired the incorporation of 14C from [14C]lactate into glucose or glycogen, and decreased the activity of the active (I) form of glycogen synthase. Cortisol treatment restored gluconeogenesis after 1 h and glycogen synthesis after 2 h. Adrenalectomy did not alter the production of glucose or lactate or the levels of gluconeogenic intermediates in livers from fasted rats perfused with fructose, but reduced the formation of glycogen from this substrate. Adrenalectomy increased the levels of lactate and decreased the levels of P-pyruvate and subsequent intermediates in the gluconeogenic pathway. These changes were reversed by cortisol treatment. It is concluded that glucocorticoids support gluconeogenesis and glycogen synthesis in livers from fasted rats primarily by facilitating a reaction(s) located between pyruvate and P-pyruvate in the gluconeogenic pathway and by promoting the conversion of inactive to active glycogen synthase."} {"id": "PMID:175664", "title": "Heart functional responses to pressure overload in exercised and sedentary rats.", "content": "Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.", "contents": "Heart functional responses to pressure overload in exercised and sedentary rats. Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function."} {"id": "PMID:175665", "title": "Viral encephalopathy mimicking functional psychosis.", "content": "Encephalitis, particularly herpes simplex encephalitis, frequently presents as a disorder with puzzling psychiatric symptoms before frank evidence of central nervous system involvement is apparent. The author describes three cases of encephalitis characterized by abrupt onset of bizarre psychological disturbance in the absence of gross neurologic dysfunction. Each patient was initially diagnosed as schizophrenic but later became critically ill and recovered only after a long and chaotic hospital course. The author warns psychiatrists and staff on psychiatric impatient units against mistakenly diagnosing cases of early encephalitis as functional psychoses.", "contents": "Viral encephalopathy mimicking functional psychosis. Encephalitis, particularly herpes simplex encephalitis, frequently presents as a disorder with puzzling psychiatric symptoms before frank evidence of central nervous system involvement is apparent. The author describes three cases of encephalitis characterized by abrupt onset of bizarre psychological disturbance in the absence of gross neurologic dysfunction. Each patient was initially diagnosed as schizophrenic but later became critically ill and recovered only after a long and chaotic hospital course. The author warns psychiatrists and staff on psychiatric impatient units against mistakenly diagnosing cases of early encephalitis as functional psychoses."} {"id": "PMID:175666", "title": "Effectiveness of educational and administrative interventions in medical outpatient clinics.", "content": "This study examines the popular belief that increased educational supervision and increased administrative support in university outpatient clinics will improve physician performance, which in turn will improve the process and outcome of patient care. Positive effects on house officers' attitudes and better functioning of clinics with respect to follow-up, information retrieval, and prescribing practices were demonstrated. However, no differences in the process and outcome of care were identified by faculty judges using implicit criteria.", "contents": "Effectiveness of educational and administrative interventions in medical outpatient clinics. This study examines the popular belief that increased educational supervision and increased administrative support in university outpatient clinics will improve physician performance, which in turn will improve the process and outcome of patient care. Positive effects on house officers' attitudes and better functioning of clinics with respect to follow-up, information retrieval, and prescribing practices were demonstrated. However, no differences in the process and outcome of care were identified by faculty judges using implicit criteria."} {"id": "PMID:175667", "title": "Coarctation of the aorta. Roentgenographic assessment after operative correction.", "content": "Persistent abnormalities in the cardiac silhouette and aortic arch are frequent in the late follow-up of patients operated upon for coarctation of the aorta. These abnormalities for the most part can be correlated with age at operation, the presence of a coexistent uncorrected congenital anomaly, or a persistent hemodynamic defect. This group of patients requires continuing clinical and roentgenologic assessment, as these abnormalities are frequently the hallmarks of additional significant cardiovascular disease despite correction of the primary congenital defect.", "contents": "Coarctation of the aorta. Roentgenographic assessment after operative correction. Persistent abnormalities in the cardiac silhouette and aortic arch are frequent in the late follow-up of patients operated upon for coarctation of the aorta. These abnormalities for the most part can be correlated with age at operation, the presence of a coexistent uncorrected congenital anomaly, or a persistent hemodynamic defect. This group of patients requires continuing clinical and roentgenologic assessment, as these abnormalities are frequently the hallmarks of additional significant cardiovascular disease despite correction of the primary congenital defect."} {"id": "PMID:175668", "title": "External and interstitial radiation therapy of carcinoma of the oral tongue. A review of 32 years' experience.", "content": "In 204 patients with squamous cell carcinoma of the oral tongue treated with radiation therapy, the most significant prognostic factors appeared to be the presence of neck lymph node metastasis on presentation and the status of the disease three months after treatment. The most common site of failure was the primary lesion, either alone or with neck disease. External irradiation alone was seldom successful. Use of peroral cone irradiation or interstitial implants, either alone or in combination with external irradiation, achieved good local control in early lesions. When the primary tumor was uncontrolled by radiation therapy, salvage with surgery was rare. When failure occurred in the neck alone, radical neck dissection was successful in the majority of cases.", "contents": "External and interstitial radiation therapy of carcinoma of the oral tongue. A review of 32 years' experience. In 204 patients with squamous cell carcinoma of the oral tongue treated with radiation therapy, the most significant prognostic factors appeared to be the presence of neck lymph node metastasis on presentation and the status of the disease three months after treatment. The most common site of failure was the primary lesion, either alone or with neck disease. External irradiation alone was seldom successful. Use of peroral cone irradiation or interstitial implants, either alone or in combination with external irradiation, achieved good local control in early lesions. When the primary tumor was uncontrolled by radiation therapy, salvage with surgery was rare. When failure occurred in the neck alone, radical neck dissection was successful in the majority of cases."} {"id": "PMID:175669", "title": "Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results.", "content": "One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy.", "contents": "Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results. One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy."} {"id": "PMID:175670", "title": "Mediastinal Hodgkin's disease.", "content": "A group of five patients with Hodgkin's disease, nodular sclerosing in type, localized to the mediastinum (Stage IA) is reported. We believe that this presentation sometimes known as \"granulomatous thymoma,\" warrants management in a manner somewhat different from that of the more common presentations of Hodgkin's disease. Nodular sclerosing Hodgkin's disease involving only the mediastinum affects a younger age group in whom the disease may be asymptomatic. Making the diagnosis may necessitate a thoracotomy, but an attempt should be made to obtain tissue short of thoracotomy, as by mediastinoscopy. An extensive attempt at surgical extirpation is not necessary because the disease is very radiosensitive and radiocurable. The combination of Stage I Hodgkin's disease, nodular sclerosing in form, limited to the mediastinum favors an excellent prognosis.", "contents": "Mediastinal Hodgkin's disease. A group of five patients with Hodgkin's disease, nodular sclerosing in type, localized to the mediastinum (Stage IA) is reported. We believe that this presentation sometimes known as \"granulomatous thymoma,\" warrants management in a manner somewhat different from that of the more common presentations of Hodgkin's disease. Nodular sclerosing Hodgkin's disease involving only the mediastinum affects a younger age group in whom the disease may be asymptomatic. Making the diagnosis may necessitate a thoracotomy, but an attempt should be made to obtain tissue short of thoracotomy, as by mediastinoscopy. An extensive attempt at surgical extirpation is not necessary because the disease is very radiosensitive and radiocurable. The combination of Stage I Hodgkin's disease, nodular sclerosing in form, limited to the mediastinum favors an excellent prognosis."} {"id": "PMID:175671", "title": "Elective irradiation with the electron beam after mastectomy for breast cancer.", "content": "From 1963 to 1970, 380 patients have received elective treatment with the electron beam after radical mastectomy for breast cancer. One hundred and twenty-nine patients received treatment to the supraclavicular and internal mammary lymph node areas only, and 251 patients received treatment to the chest wall as well as to the areas of peripheral lymphatic drainage. Analysis of the results shows the value of elective irradiation of occult deposits of disease since the incidence of local recurrences is significantly less than would be anticipated in this group of patients.", "contents": "Elective irradiation with the electron beam after mastectomy for breast cancer. From 1963 to 1970, 380 patients have received elective treatment with the electron beam after radical mastectomy for breast cancer. One hundred and twenty-nine patients received treatment to the supraclavicular and internal mammary lymph node areas only, and 251 patients received treatment to the chest wall as well as to the areas of peripheral lymphatic drainage. Analysis of the results shows the value of elective irradiation of occult deposits of disease since the incidence of local recurrences is significantly less than would be anticipated in this group of patients."} {"id": "PMID:175672", "title": "Treatment selection in primary breast cancer. Pathologic considerations.", "content": "Minimal breast cancer is defined as including in situ lobular carcinoma, noninvasive intraductal carcinoma, and invasive carcinoma forming a mass no greater than 0.5 cm in diameter. Intraductal, intralobular, and microinvasive carcinomas of this degree of development are classed together, and are associated with at most a 10% probability of having associated axillary lymph node involvement. Lesions of this classification have been shown to have a five year survival rate of 97% and a ten year rate of 95%, when they are treated surgically.", "contents": "Treatment selection in primary breast cancer. Pathologic considerations. Minimal breast cancer is defined as including in situ lobular carcinoma, noninvasive intraductal carcinoma, and invasive carcinoma forming a mass no greater than 0.5 cm in diameter. Intraductal, intralobular, and microinvasive carcinomas of this degree of development are classed together, and are associated with at most a 10% probability of having associated axillary lymph node involvement. Lesions of this classification have been shown to have a five year survival rate of 97% and a ten year rate of 95%, when they are treated surgically."} {"id": "PMID:175673", "title": "Treatment, results and prognostic factors in stage I and II sarcomas of the corpus uteri.", "content": "One-hundred and four cases of Stage I and II uterine sarcomas treated at Rosewell Park Memorial Institute over a 27 year period are reviewed. Included are 30 cases of mixed mesodermal tumor, 27 cases of carcinosarcoma, 25 cases of endometrial stromal sarcoma, and 22 cases of leiomyosarcoma. Prognostic factors were found to include histologic classification, stage, uterine size, depth of myometrial invasion, and type of treatment. Endometrial stromal sarcomas had the best over-all prognosis. Radiation therapy alone was inadequate treatment, but was of adjunctive value to surgery in terms of increasing survival and decreasing pelvic recurrences in patients with endometrial stromal sarcoma, mixed mesodermal tumor, and carcinosarcoma. Patients with leiomyosarcoma did not benefit from adjunctive radiation therapy.", "contents": "Treatment, results and prognostic factors in stage I and II sarcomas of the corpus uteri. One-hundred and four cases of Stage I and II uterine sarcomas treated at Rosewell Park Memorial Institute over a 27 year period are reviewed. Included are 30 cases of mixed mesodermal tumor, 27 cases of carcinosarcoma, 25 cases of endometrial stromal sarcoma, and 22 cases of leiomyosarcoma. Prognostic factors were found to include histologic classification, stage, uterine size, depth of myometrial invasion, and type of treatment. Endometrial stromal sarcomas had the best over-all prognosis. Radiation therapy alone was inadequate treatment, but was of adjunctive value to surgery in terms of increasing survival and decreasing pelvic recurrences in patients with endometrial stromal sarcoma, mixed mesodermal tumor, and carcinosarcoma. Patients with leiomyosarcoma did not benefit from adjunctive radiation therapy."} {"id": "PMID:175674", "title": "Irradiation of endometrial cancer in patients with medical contraindication to surgery or with unresectable lesions.", "content": "In 124 medically inoperable patients with endometrial cancer, the five and ten year actuarial survival rates were 68% and 57%. In 26 patients with technically unresectable endometrial cancer, 26% actuarial survival rates at both five and ten years were seen. Pelvic control at death was 89% in Stage Ia, 78% in Stage Ib, 82% in Stage II, and 62% in Stage III. Sophisticated intracavitary therapy alone or in conjunction with external irradiation appears to give better uterine control rates than does external irradiation alone.", "contents": "Irradiation of endometrial cancer in patients with medical contraindication to surgery or with unresectable lesions. In 124 medically inoperable patients with endometrial cancer, the five and ten year actuarial survival rates were 68% and 57%. In 26 patients with technically unresectable endometrial cancer, 26% actuarial survival rates at both five and ten years were seen. Pelvic control at death was 89% in Stage Ia, 78% in Stage Ib, 82% in Stage II, and 62% in Stage III. Sophisticated intracavitary therapy alone or in conjunction with external irradiation appears to give better uterine control rates than does external irradiation alone."} {"id": "PMID:175675", "title": "Experience with twice-a-day fractionation in clinical radiotherapy.", "content": "Theoretical reasons have led to the treatment of 24 patients with advanced, rapidly growing squamous cell carcinomas of the head and neck, and 17 patients with inflammatory carcinoma of the breast with twice-a-day fractionation. After initial reduction in dose in both series, acute reactions and sequelae are similar to those in conventionally treated patients. The relative control rates are better than would be expected from conventional irradiation.", "contents": "Experience with twice-a-day fractionation in clinical radiotherapy. Theoretical reasons have led to the treatment of 24 patients with advanced, rapidly growing squamous cell carcinomas of the head and neck, and 17 patients with inflammatory carcinoma of the breast with twice-a-day fractionation. After initial reduction in dose in both series, acute reactions and sequelae are similar to those in conventionally treated patients. The relative control rates are better than would be expected from conventional irradiation."} {"id": "PMID:175676", "title": "Volume and time factors in interstitial gamma-ray therapy.", "content": "The two suppositions which have dictated time-dose and volume relationships in interstitial gamma ray implantation have been examined in the light of recent publications. The first of these assumptions, that total dose reduction is required when the dose rate exceeds 6,000-7,000 rads in seven days, does not appear to be substantiated by clinical experiences. It appears that total dose is the critical treatment parameter and that dose rate may be increased by a factor of two or three without requiring alteration of the total dose. Although the second classical assumption, \"volume increase requires dose decrease,\" has been shown throughout radiation therapy experience to be generally correct, it should not be applied rigidly to interstitial gamma-ray therapy. In fact, recent experiences seem to indicate that compensation with respect to volume is not an absolute necessity. Larger lesions require, if anything, higher doses than small ones. To obtain a high percentage of controlled, lesions there must be no dose reduction, regardless of increased volume treated.", "contents": "Volume and time factors in interstitial gamma-ray therapy. The two suppositions which have dictated time-dose and volume relationships in interstitial gamma ray implantation have been examined in the light of recent publications. The first of these assumptions, that total dose reduction is required when the dose rate exceeds 6,000-7,000 rads in seven days, does not appear to be substantiated by clinical experiences. It appears that total dose is the critical treatment parameter and that dose rate may be increased by a factor of two or three without requiring alteration of the total dose. Although the second classical assumption, \"volume increase requires dose decrease,\" has been shown throughout radiation therapy experience to be generally correct, it should not be applied rigidly to interstitial gamma-ray therapy. In fact, recent experiences seem to indicate that compensation with respect to volume is not an absolute necessity. Larger lesions require, if anything, higher doses than small ones. To obtain a high percentage of controlled, lesions there must be no dose reduction, regardless of increased volume treated."} {"id": "PMID:175677", "title": "Low energy radionuclides for permanent interstitial implantation.", "content": "An analysis of 318 permanent implants was carried out in an attempt to establish the effectiveness of iodine 125 as compared with radon 222 and iridium 192; and to derive dose-response curves for iodine 125. Analysis of the clinical results obtained with iodine 125 in comparison with radon 222 and iridium 192 in selected anatomical sites demonstrated that iodine 125 has a higher therapeutic ratio than the other two radionuclides. A tumor control rate of at least 80% with iodine 125 implants might be expected after a good geometrical dose distribution, with a planned initial minimum tumor dose of at least 14,000 +/- 2,000 rads. Rapid tumor shrinkage ensures a more or less steady or even increased dose rate over a period of several weeks and improves the local tumor control. Tumors with a longer cell cycle are especially susceptible to irradiation with radionuclides of long half-lives.", "contents": "Low energy radionuclides for permanent interstitial implantation. An analysis of 318 permanent implants was carried out in an attempt to establish the effectiveness of iodine 125 as compared with radon 222 and iridium 192; and to derive dose-response curves for iodine 125. Analysis of the clinical results obtained with iodine 125 in comparison with radon 222 and iridium 192 in selected anatomical sites demonstrated that iodine 125 has a higher therapeutic ratio than the other two radionuclides. A tumor control rate of at least 80% with iodine 125 implants might be expected after a good geometrical dose distribution, with a planned initial minimum tumor dose of at least 14,000 +/- 2,000 rads. Rapid tumor shrinkage ensures a more or less steady or even increased dose rate over a period of several weeks and improves the local tumor control. Tumors with a longer cell cycle are especially susceptible to irradiation with radionuclides of long half-lives."} {"id": "PMID:175678", "title": "Gallium-67 scans in children with solid tumors.", "content": "Twenty pediatric patients with malignant disease were studied by whole body gallium scans. Seven had Hodgkin's disease, five had soft tissue sarcomas, three had neuroblastomas, two had Wilm's tumors, and one each had a hepatoblastoma, embryonal cell carcinoma, and sacrococcygeal teratoma. Of 50 sites studied, there was a true positive result in 17%, and in 58% there were false negative results. The method served best in patients with Hodgkin's disease, where the true positive rate was 64%. In no instance did the gallium scan affect the clinical management of a patient.", "contents": "Gallium-67 scans in children with solid tumors. Twenty pediatric patients with malignant disease were studied by whole body gallium scans. Seven had Hodgkin's disease, five had soft tissue sarcomas, three had neuroblastomas, two had Wilm's tumors, and one each had a hepatoblastoma, embryonal cell carcinoma, and sacrococcygeal teratoma. Of 50 sites studied, there was a true positive result in 17%, and in 58% there were false negative results. The method served best in patients with Hodgkin's disease, where the true positive rate was 64%. In no instance did the gallium scan affect the clinical management of a patient."} {"id": "PMID:175680", "title": "Idiopathic multicentric osteolysis.", "content": "A 59 year old while female with striking carpal and tarsal osteolysis is reported. The process primarily involves the carpals and tarsals but includes other sites. The pertinent literature is reviewed and a simplified classification of idiopathic multicentric osteolysis is presented. Idiopathic multicentric osteolysis may be sporadic but can demonstrate either dominant or recessive inheritance. There may or may not be associated nephropathy. The underlying mechanism appears similar in all variations of this condition. Gorham's disease, the Winchester syndrome, and other osteolytic conditions which may predominantly affect the tarsal and carpal bones most likely are totally different processes, unrelated to idiopathic multicentric osteolysis.", "contents": "Idiopathic multicentric osteolysis. A 59 year old while female with striking carpal and tarsal osteolysis is reported. The process primarily involves the carpals and tarsals but includes other sites. The pertinent literature is reviewed and a simplified classification of idiopathic multicentric osteolysis is presented. Idiopathic multicentric osteolysis may be sporadic but can demonstrate either dominant or recessive inheritance. There may or may not be associated nephropathy. The underlying mechanism appears similar in all variations of this condition. Gorham's disease, the Winchester syndrome, and other osteolytic conditions which may predominantly affect the tarsal and carpal bones most likely are totally different processes, unrelated to idiopathic multicentric osteolysis."} {"id": "PMID:175681", "title": "Myositis ossificans circumscripta: a benign lesion with a malignant differential diagnosis.", "content": "Localized areas of active myositis ossificans, occurring without a clear history of antecedent trauma, have been referred to as a \"pseudo-malignant osseous tumor of soft tissue.\" This lesion may be mistaken both roentgenographically and pathologically for a malignancy. The roentgenographic signs which favor a diagnosis of non-neoplastic heterotopic bone formation include a lucent zone between the lesion and the adjacent bone, an intact underlying cortex, diaphyseal location, dense calcification in the periphery, and loss of volume on serial films.", "contents": "Myositis ossificans circumscripta: a benign lesion with a malignant differential diagnosis. Localized areas of active myositis ossificans, occurring without a clear history of antecedent trauma, have been referred to as a \"pseudo-malignant osseous tumor of soft tissue.\" This lesion may be mistaken both roentgenographically and pathologically for a malignancy. The roentgenographic signs which favor a diagnosis of non-neoplastic heterotopic bone formation include a lucent zone between the lesion and the adjacent bone, an intact underlying cortex, diaphyseal location, dense calcification in the periphery, and loss of volume on serial films."} {"id": "PMID:175682", "title": "Lesions resembling gout in patients with rheumatoid arthritis.", "content": "Although roentgenographic appearances are seldom important in establishing the diagnosis of rheumatoid arthritis or gout, atypical appearances of individual lesions may confuse the distinction between these two conditions. Sixteen patients with rheumatoid arthritis were selected to illustrate joint and soft tissue lesions which resemble gout. The lesions are divided into five broad categories on the basis of the appearance and sites of bone erosion as well as the nature of soft tissue changes. Symmetrical bilateral joint involvement was found to be especially helpful in distinguishing rheumatoid arthritis from gout.", "contents": "Lesions resembling gout in patients with rheumatoid arthritis. Although roentgenographic appearances are seldom important in establishing the diagnosis of rheumatoid arthritis or gout, atypical appearances of individual lesions may confuse the distinction between these two conditions. Sixteen patients with rheumatoid arthritis were selected to illustrate joint and soft tissue lesions which resemble gout. The lesions are divided into five broad categories on the basis of the appearance and sites of bone erosion as well as the nature of soft tissue changes. Symmetrical bilateral joint involvement was found to be especially helpful in distinguishing rheumatoid arthritis from gout."} {"id": "PMID:175683", "title": "Bronchopulmonary foregut malformations. A unifying etiological concept.", "content": "Two cases of congenital bronchopulmonary foregut malformation are reported and another 27 cases reviewed and the findings analyzed. The left lower lobe and the entire right lung are the most common locations of pulmonary involvement. The distal portion of the esophagus or cardioesophageal junction was the most common site of communication (83%). The majority of the patients (60%) presented in the first eight months of life, and the incidence in females was nearly twice that in males. Chronic cough, recurrent pneumonias and respiratory distress were the most common clinical findings, whereas two patients were totally asymptomatic. The esophagogram was the single most useful diagnostic procedure (82%). The microscopic structure of the congenital fistula resembled esophagus, bronchus or both. Surgical treatment was curative in most instances. Sime deaths occurred prior to corrective surgery, whereas the postoperative deaths in most instances were related to severe associated congenital anomalies. We believe a common embryologic pathogenesis leads to the formation of a variety of bronchopulmonary foregut malformations. These bronchopulmonary foregut malformations include intralobar and extralobar sequestrations, pulmonary sequestration with patent, or involuted--partial or complete--gastroesophageal communication, esophageal or gastric diverticula, and esophageal or bronchogenic duplication cysts.", "contents": "Bronchopulmonary foregut malformations. A unifying etiological concept. Two cases of congenital bronchopulmonary foregut malformation are reported and another 27 cases reviewed and the findings analyzed. The left lower lobe and the entire right lung are the most common locations of pulmonary involvement. The distal portion of the esophagus or cardioesophageal junction was the most common site of communication (83%). The majority of the patients (60%) presented in the first eight months of life, and the incidence in females was nearly twice that in males. Chronic cough, recurrent pneumonias and respiratory distress were the most common clinical findings, whereas two patients were totally asymptomatic. The esophagogram was the single most useful diagnostic procedure (82%). The microscopic structure of the congenital fistula resembled esophagus, bronchus or both. Surgical treatment was curative in most instances. Sime deaths occurred prior to corrective surgery, whereas the postoperative deaths in most instances were related to severe associated congenital anomalies. We believe a common embryologic pathogenesis leads to the formation of a variety of bronchopulmonary foregut malformations. These bronchopulmonary foregut malformations include intralobar and extralobar sequestrations, pulmonary sequestration with patent, or involuted--partial or complete--gastroesophageal communication, esophageal or gastric diverticula, and esophageal or bronchogenic duplication cysts."} {"id": "PMID:175685", "title": "Neuroepithelial (colloid) cysts. Pathogenesis and unusual features.", "content": "A brief history of the theories of pathogenesis of the origin of neuroepithelial cysts is presented. An origin more diffuse than the paraphysis seems most likely in our opinion, and we attempt to substantiate this theory with several of the cases from our series. One posterior third ventricular neuroepithelial cyst and one in the fourth ventricle are demonstrated roentgenographically. Also included in our series are a case showing suprasellar calcification on plain skull roentgenograms, not previously reported in neuroepithelial cysts, and a case with a cyst measuring 9 cm, the largest neuroepithelial cyst yet reported.", "contents": "Neuroepithelial (colloid) cysts. Pathogenesis and unusual features. A brief history of the theories of pathogenesis of the origin of neuroepithelial cysts is presented. An origin more diffuse than the paraphysis seems most likely in our opinion, and we attempt to substantiate this theory with several of the cases from our series. One posterior third ventricular neuroepithelial cyst and one in the fourth ventricle are demonstrated roentgenographically. Also included in our series are a case showing suprasellar calcification on plain skull roentgenograms, not previously reported in neuroepithelial cysts, and a case with a cyst measuring 9 cm, the largest neuroepithelial cyst yet reported."} {"id": "PMID:175686", "title": "Optimal tomographic technique to demonstrate common bile duct stones. An in vitro study.", "content": "Six degree and 10 degree circular modes represent the optimal methods available for intravenous cholangiography with tomography within the technical limitations and constraints outlined in this study. The 10 degree mode is superior in the presence of superimposed gas. Ten degree linear tomography is an efficient method for determining the level of the common bile duct but is not the optimal method for obtaining image detail. Thin secretion unidirectional or pleuridirectional modes are occasionally helpful in delineating fine details. The zone of focus is very narrow, permitting very limited sampling within the usual zone of interest. These modes are inefficient in determining the level of the duct and produce less useful image detail than 10 degree circular tomography for ducts of normal, or slightly larger than normal diameters. They are seldom indicated as the primary modality in tomography of the common bile duct.", "contents": "Optimal tomographic technique to demonstrate common bile duct stones. An in vitro study. Six degree and 10 degree circular modes represent the optimal methods available for intravenous cholangiography with tomography within the technical limitations and constraints outlined in this study. The 10 degree mode is superior in the presence of superimposed gas. Ten degree linear tomography is an efficient method for determining the level of the common bile duct but is not the optimal method for obtaining image detail. Thin secretion unidirectional or pleuridirectional modes are occasionally helpful in delineating fine details. The zone of focus is very narrow, permitting very limited sampling within the usual zone of interest. These modes are inefficient in determining the level of the duct and produce less useful image detail than 10 degree circular tomography for ducts of normal, or slightly larger than normal diameters. They are seldom indicated as the primary modality in tomography of the common bile duct."} {"id": "PMID:175687", "title": "Successful intravenous cholecystocholangiography in the jaundiced patient using meglumine iodoxamate (Cholovue).", "content": "A clinical trial of meglumine iodoxamate (Cholovue) for intravenous cholangiocholecystography in 18 patients with elevated levels of serum bilirubin was performed. Ten to 30 cc of a 40% aqueous solution of the agent were given intravenously over a ten minute period and roentgenographic examinations conducted to document the agent's effectiveness, to determine optimal levels of dose, and to assess its safety. Common bile duct and gallbladder visualization was obtained in a surprisingly large number. The agent was effective with bilirubin levels up to 6.5 mg %. The optimal dose in patients with elevated bilirubin is probably in the range of 20 cc. Despite intensive monitoring, there were no important adverse clinical nor laboratory reactions observed. The new agent appears to offer a significant improvement over Cholografin, particularly with respect to patients with elevated bilirubin levels.", "contents": "Successful intravenous cholecystocholangiography in the jaundiced patient using meglumine iodoxamate (Cholovue). A clinical trial of meglumine iodoxamate (Cholovue) for intravenous cholangiocholecystography in 18 patients with elevated levels of serum bilirubin was performed. Ten to 30 cc of a 40% aqueous solution of the agent were given intravenously over a ten minute period and roentgenographic examinations conducted to document the agent's effectiveness, to determine optimal levels of dose, and to assess its safety. Common bile duct and gallbladder visualization was obtained in a surprisingly large number. The agent was effective with bilirubin levels up to 6.5 mg %. The optimal dose in patients with elevated bilirubin is probably in the range of 20 cc. Despite intensive monitoring, there were no important adverse clinical nor laboratory reactions observed. The new agent appears to offer a significant improvement over Cholografin, particularly with respect to patients with elevated bilirubin levels."} {"id": "PMID:175688", "title": "Griffiths' point: critical anastomosis at the splenic flexure. Significance in ischemia of the colon.", "content": "Griffiths' point is defined as the site of (a) communication of the ascending left colic artery with the marginal artery of Drummond, and (b) anastomotic bridging between the right and left terminal branches of the ascending left colic artery at the splenic flexure of the colon. It is upon this critical point at the splenic flexure that collateral circulation between the superior mesenteric artery and the marginal artery branch of the inferior mesenteric artery supplying the descending colon is dependent. Analysis of arteriographic studies shows that anastomosis at Griffiths' point is present in 48%, poor or tenuous in nine percent, and absent in 43%. This critical point is of significance in occlusive vascular impairment of the left colon, both in spontaneous instances and following surgical ligation of the inferior mesenteric artery, and in \"nonocclusive\" ischemic colitis. Its relationship to arteriosclerotic stenoses and low flow states is discussed. Individuals with absence of dependable anastomoses at Griffiths' point at the splenic flexure may be particularly vulnerable to low perfusion states and develop the syndrome of ischemic colitis. Complete arteriographic evaluation is necessary in ischemia of the colon. This includes particularly assessment of atherosclerotic changes at or near the ostia of the major visceral arteries and the vascular arrangement at Griffiths' point.", "contents": "Griffiths' point: critical anastomosis at the splenic flexure. Significance in ischemia of the colon. Griffiths' point is defined as the site of (a) communication of the ascending left colic artery with the marginal artery of Drummond, and (b) anastomotic bridging between the right and left terminal branches of the ascending left colic artery at the splenic flexure of the colon. It is upon this critical point at the splenic flexure that collateral circulation between the superior mesenteric artery and the marginal artery branch of the inferior mesenteric artery supplying the descending colon is dependent. Analysis of arteriographic studies shows that anastomosis at Griffiths' point is present in 48%, poor or tenuous in nine percent, and absent in 43%. This critical point is of significance in occlusive vascular impairment of the left colon, both in spontaneous instances and following surgical ligation of the inferior mesenteric artery, and in \"nonocclusive\" ischemic colitis. Its relationship to arteriosclerotic stenoses and low flow states is discussed. Individuals with absence of dependable anastomoses at Griffiths' point at the splenic flexure may be particularly vulnerable to low perfusion states and develop the syndrome of ischemic colitis. Complete arteriographic evaluation is necessary in ischemia of the colon. This includes particularly assessment of atherosclerotic changes at or near the ostia of the major visceral arteries and the vascular arrangement at Griffiths' point."} {"id": "PMID:175689", "title": "Angiography and ultrasonography. A comparative study of abdominal aortic aneurysms.", "content": "Ultrasound is presently the diagnostic procedure of choice in pulsatile abdominal masses. The ease and accuracy of this method have many advantages over aortography, and ultrasonography can accurately define the size of an abdominal aortic aneruysm. In addition, a normal aorta with an overlying mass, or a tortuous aorta which feels unusually prominent, can be detected, and aortography may not be necessary. Although ultrasound can detect involvement of iliac arteries, it does not allow assessment of the position of the aneurysm relative to the renal arteries, or detect involvement of other branch vessels of the aorta. Ultrasound is more accurate that clinical examination, plain roentgenography, aortography, or isotope aortography in the diagnosis of abdominal aortic aneurysms.", "contents": "Angiography and ultrasonography. A comparative study of abdominal aortic aneurysms. Ultrasound is presently the diagnostic procedure of choice in pulsatile abdominal masses. The ease and accuracy of this method have many advantages over aortography, and ultrasonography can accurately define the size of an abdominal aortic aneruysm. In addition, a normal aorta with an overlying mass, or a tortuous aorta which feels unusually prominent, can be detected, and aortography may not be necessary. Although ultrasound can detect involvement of iliac arteries, it does not allow assessment of the position of the aneurysm relative to the renal arteries, or detect involvement of other branch vessels of the aorta. Ultrasound is more accurate that clinical examination, plain roentgenography, aortography, or isotope aortography in the diagnosis of abdominal aortic aneurysms."} {"id": "PMID:175691", "title": "Combination of conservative surgery and irradiation for cancer of the breast.", "content": "In patients with relatively advanced local or axillary disease, or both, a simple mastectomy followed by irradiation gives the best local and regional control rates. From the existing data, one can state unreservedly that women with early breast cancer take no chance on their life by having a treatment method which preserves the breast. In conjunction with the wedge excision, even if the axilla is clinically negative, a dissection of the low and central axilla brings enough information to decide on elective chemotherapy.", "contents": "Combination of conservative surgery and irradiation for cancer of the breast. In patients with relatively advanced local or axillary disease, or both, a simple mastectomy followed by irradiation gives the best local and regional control rates. From the existing data, one can state unreservedly that women with early breast cancer take no chance on their life by having a treatment method which preserves the breast. In conjunction with the wedge excision, even if the axilla is clinically negative, a dissection of the low and central axilla brings enough information to decide on elective chemotherapy."} {"id": "PMID:175692", "title": "Squamous cell carcinoma of the oral tongue and floor of mouth. Evaluation of interstitial radium therapy.", "content": "From January, 1965, to December, 1972, 46 patients with squamous cell carcinoma of the floor of the mouth and 102 patients with squamous cell carcinoma of the oral tongue were treated at M.D. Anderson Hospital and Tumor Institute by interstitial irradiation alone or in combination with external irradiation. Through the years the combination of radiation therapy modalities has been adjusted in an attempt to improve local control, keeping complications to a minimum. In this paper we analyze local control, causes of failure and complications as related to the primary size (T stage) and radiation therapy techniques employed.", "contents": "Squamous cell carcinoma of the oral tongue and floor of mouth. Evaluation of interstitial radium therapy. From January, 1965, to December, 1972, 46 patients with squamous cell carcinoma of the floor of the mouth and 102 patients with squamous cell carcinoma of the oral tongue were treated at M.D. Anderson Hospital and Tumor Institute by interstitial irradiation alone or in combination with external irradiation. Through the years the combination of radiation therapy modalities has been adjusted in an attempt to improve local control, keeping complications to a minimum. In this paper we analyze local control, causes of failure and complications as related to the primary size (T stage) and radiation therapy techniques employed."} {"id": "PMID:175693", "title": "Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study.", "content": "In 1961, a randomized study was begun at the University of Wisconsin Medical Center in which the treatment of advanced squamous cell carcinoma of the head and neck with radiation therapy was compared with combined treatment with radiation therapy and 5-Fluorouracil. One hundred and thirty-six patients with primary lesions in the oral cavity, the base of the tongue, and the oropharynx were analyzed. Both local control and survival were better in the combined treatment group than in the group with radiation therapy alone. However, in only the oral cavity patient population was the difference statistically significant. Both acute and late complications were also increased in this group of patients who received combined treatment.", "contents": "Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study. In 1961, a randomized study was begun at the University of Wisconsin Medical Center in which the treatment of advanced squamous cell carcinoma of the head and neck with radiation therapy was compared with combined treatment with radiation therapy and 5-Fluorouracil. One hundred and thirty-six patients with primary lesions in the oral cavity, the base of the tongue, and the oropharynx were analyzed. Both local control and survival were better in the combined treatment group than in the group with radiation therapy alone. However, in only the oral cavity patient population was the difference statistically significant. Both acute and late complications were also increased in this group of patients who received combined treatment."} {"id": "PMID:175694", "title": "Carcinoma of the oropharynx. Results of megavoltage radiation therapy in 305 patients.", "content": "Three hundred and five patients with oropharyngeal carcinomas received linear accelerator radiation therapy at the Stanford University Medical Center between 1956 and 1973. All were staged by the TNM system, using the UICC Classification of 1962. Actuarial five year survival for patients with tonsil cancers ranged from 50% to 18% for those with T1 and T3 lesions, respectively. Disease-free survival was higher than actuarial survival for patients with T1 and T2 lesions, reflecting an alteration of the latter curves by deaths from intercurrent diseases and second primary malignancies. Actuarial survival for patients with base of the tongue carcinomas was approximately 35% for those with T1 and T2 primary lesions and 22% for patients with T3 carcinomas. Considering all oropharyngeal sites of involvement together, clinically involved cervical lymph nodes were controlled by radiation therapy alone in 60 of 91 patients with N1 nodal involvement (67%), in twelve of 25 with N2 neck disease (48%) and in 46% of those patients with N3 involvement (34 of 74). Eighty-nine percent of patients whose lymph nodes were not controlled by radiation therapy alone also had uncontrolled primary cancers. Over 90% of the patients whole cervical lymph nodes were initially uninvolved remained free of late nodal metastases if at least the regional (first echelon) lymph nodes were included in the primary treatment fields. The results of a randomized trial which compared surgery and radiation therapy alone and the two modalities in combination for the treatment of a limited number of patients with advanced cancers of the oropharynx, supraglottic larynx and hypopharynx suggest that surgery alone is not the treatment of choice.", "contents": "Carcinoma of the oropharynx. Results of megavoltage radiation therapy in 305 patients. Three hundred and five patients with oropharyngeal carcinomas received linear accelerator radiation therapy at the Stanford University Medical Center between 1956 and 1973. All were staged by the TNM system, using the UICC Classification of 1962. Actuarial five year survival for patients with tonsil cancers ranged from 50% to 18% for those with T1 and T3 lesions, respectively. Disease-free survival was higher than actuarial survival for patients with T1 and T2 lesions, reflecting an alteration of the latter curves by deaths from intercurrent diseases and second primary malignancies. Actuarial survival for patients with base of the tongue carcinomas was approximately 35% for those with T1 and T2 primary lesions and 22% for patients with T3 carcinomas. Considering all oropharyngeal sites of involvement together, clinically involved cervical lymph nodes were controlled by radiation therapy alone in 60 of 91 patients with N1 nodal involvement (67%), in twelve of 25 with N2 neck disease (48%) and in 46% of those patients with N3 involvement (34 of 74). Eighty-nine percent of patients whose lymph nodes were not controlled by radiation therapy alone also had uncontrolled primary cancers. Over 90% of the patients whole cervical lymph nodes were initially uninvolved remained free of late nodal metastases if at least the regional (first echelon) lymph nodes were included in the primary treatment fields. The results of a randomized trial which compared surgery and radiation therapy alone and the two modalities in combination for the treatment of a limited number of patients with advanced cancers of the oropharynx, supraglottic larynx and hypopharynx suggest that surgery alone is not the treatment of choice."} {"id": "PMID:175695", "title": "Non-randomized comparison of preoperative irradiation and surgery versus irradiation alone in the management of carcinoma of the tonsil.", "content": "This is a non-randomized comparison of 98 patients with epidermoid carcinoma of the tonsil treated by preoperative irradiation and surgery and 97 patients receiving irradiation alone. Patients treated with preoperative irradiation received, in most instances, 3,000 rads tumor dose in three weeks through ipsilateral portals, followed within two to six weeks after completion of therapy by an en bloc tumor resection and radical neck dissection. The group treated with irradiation alone received tumor doses in the range of 5,500-6,500 rads in six weeks. No significant difference was noted in the survival yielded by either treatment modality. Both treatment modalities were equally effective in controlling the tumor in the metastatic ipsilateral lymph nodes. In selected cases, a combination of both modalitites may offer better results, but this remains to be proved.", "contents": "Non-randomized comparison of preoperative irradiation and surgery versus irradiation alone in the management of carcinoma of the tonsil. This is a non-randomized comparison of 98 patients with epidermoid carcinoma of the tonsil treated by preoperative irradiation and surgery and 97 patients receiving irradiation alone. Patients treated with preoperative irradiation received, in most instances, 3,000 rads tumor dose in three weeks through ipsilateral portals, followed within two to six weeks after completion of therapy by an en bloc tumor resection and radical neck dissection. The group treated with irradiation alone received tumor doses in the range of 5,500-6,500 rads in six weeks. No significant difference was noted in the survival yielded by either treatment modality. Both treatment modalities were equally effective in controlling the tumor in the metastatic ipsilateral lymph nodes. In selected cases, a combination of both modalitites may offer better results, but this remains to be proved."} {"id": "PMID:175696", "title": "Initial comparative response to peak pions and x-rays of normal skin and underlying tissue surrounding superficial metastatic nodules.", "content": "Given the limitations of available material and methods for measuring skin response, the relative biological effectivenss (RBE) for the development and healing of skin reaction to pions in this experiment is 1.43. This is based on data obtained from a patient with malignant melanoma, in whom multiple skin nodules and the surrounding normal skin were randomized into three dose levels for pions and x-rays. The RBE for skin reaction was obtained while the skin tumor nodules appeared to regress at least as rapidly with pion therapy as with x-rays. Without benefit of adequate observation of time required for nodule regrowth, any estimate of tumor RBE is speculative.", "contents": "Initial comparative response to peak pions and x-rays of normal skin and underlying tissue surrounding superficial metastatic nodules. Given the limitations of available material and methods for measuring skin response, the relative biological effectivenss (RBE) for the development and healing of skin reaction to pions in this experiment is 1.43. This is based on data obtained from a patient with malignant melanoma, in whom multiple skin nodules and the surrounding normal skin were randomized into three dose levels for pions and x-rays. The RBE for skin reaction was obtained while the skin tumor nodules appeared to regress at least as rapidly with pion therapy as with x-rays. Without benefit of adequate observation of time required for nodule regrowth, any estimate of tumor RBE is speculative."} {"id": "PMID:175697", "title": "Initial evaluation of reduced fractionation in the irradiation of malignant epithelial tumors.", "content": "From July, 1971, through June, 1974, 170 patients underwent radiation therapy with reduced fractionation at the Milwaukee County General Hospital and the Wood Veterans Administration Hospital. One or two fractions per week were delivered for five to seven weeks to a total dose based on the tolerance of normal tissues predicted by the nominal standard dose (NSD) hypothesis of Ellis. Three groups of patients were selected from this heterogeneous population for detailed analysis--carcinomas of the skin, breast, and lung. The 72 patients evaluated provide useful data in regard to acute and subacute reactions. Short term assessment of local tumor control in relation to surrounding normal tissue response is similar to that with conventional fractionation for each of these malignant epithelial tumors.", "contents": "Initial evaluation of reduced fractionation in the irradiation of malignant epithelial tumors. From July, 1971, through June, 1974, 170 patients underwent radiation therapy with reduced fractionation at the Milwaukee County General Hospital and the Wood Veterans Administration Hospital. One or two fractions per week were delivered for five to seven weeks to a total dose based on the tolerance of normal tissues predicted by the nominal standard dose (NSD) hypothesis of Ellis. Three groups of patients were selected from this heterogeneous population for detailed analysis--carcinomas of the skin, breast, and lung. The 72 patients evaluated provide useful data in regard to acute and subacute reactions. Short term assessment of local tumor control in relation to surrounding normal tissue response is similar to that with conventional fractionation for each of these malignant epithelial tumors."} {"id": "PMID:175698", "title": "Patterns of failure in intracranial astrocytomas after irradiation: analysis of dose and field factors.", "content": "The choice of tumor dose and treatment volume are the two most important radiation factors influencing survival in glioblastomas. Patients treated to their whole brain survive longer than those treated with limited fields. Glioblastomas treated with over 5,000 rads (1,300 rets) survive longer than those treated with smaller doses. Other factors affecting survival are: the pathological grade; age at diagnosis; and surgical treatment performed. Failure patterns in glioblastomas represent intrinsic qualities of the tumor, the host, and the treatment employed. They dictate the strategy to follow. Perhaps some of these are unaffected by irradiation. An increase in dose and the extension of fields in glioblastomas have produced a gain in both the quantity and the quality of survival. The whole brain is treated (5,000-6,000 rads) and the target volume is boosted to 7,000 to 8,000 rads. Grade II astrocytomas perhaps should be treated with whole brain irradiation (4,500 rads) and a boost to the target volume of an additional 1,000 rads.", "contents": "Patterns of failure in intracranial astrocytomas after irradiation: analysis of dose and field factors. The choice of tumor dose and treatment volume are the two most important radiation factors influencing survival in glioblastomas. Patients treated to their whole brain survive longer than those treated with limited fields. Glioblastomas treated with over 5,000 rads (1,300 rets) survive longer than those treated with smaller doses. Other factors affecting survival are: the pathological grade; age at diagnosis; and surgical treatment performed. Failure patterns in glioblastomas represent intrinsic qualities of the tumor, the host, and the treatment employed. They dictate the strategy to follow. Perhaps some of these are unaffected by irradiation. An increase in dose and the extension of fields in glioblastomas have produced a gain in both the quantity and the quality of survival. The whole brain is treated (5,000-6,000 rads) and the target volume is boosted to 7,000 to 8,000 rads. Grade II astrocytomas perhaps should be treated with whole brain irradiation (4,500 rads) and a boost to the target volume of an additional 1,000 rads."} {"id": "PMID:175699", "title": "Pharmaco-kinetics of current skeletal-seeking radiopharmaceuticals.", "content": "The blood clearance of all current bone-seeking radiopharmaceuticals is biexponential during the first four hours after injection. Exponent I represents bone uptake and its clearance half-time is less than 30 min. Exponent II represents mainly urinary excretion and its clearance half-time varies from 168 to 512 min. The blood background is highest with 99mTc-labeled polyphosphate (Tc-Poly) and lowest with sodium fluoride (F-18); 99mTc-labeled diphosphonate (Tc-Dip) and 99mTc-labeled pyrophosphate (Tc-Pyro) show intermediate blood levels. The slower blood clearance of 99mTc-phosphate complexes in comparison with F-18 is due primarily to their increased protein binding. Tc-Poly blood clearance, which is slower than that of Tc-Dip and Tc-Pyro, is due primarily to its increased red cell binding and the larger size of its molecule. Bone uptake and urinary excretion of all 99mTc-labeled phosphate complexes are approximately the same: in the range of six to ten per cent in the blood, 30-33% in the urine, and 55-58 percent in the bone and other tissues. F-18 concentration in the bone is almost 1.5 times that of the 99mTc-labeled phosphate complexes. The sensitivity and resolution of lesions are identical for all 99mTc-labeled phosphate complexes and are far better than those for F-18. No toxicity is noted with the amount of phosphate present in the marketed kits, and it appears reasonable to use the minimal amount so long as efficiency is not compromised.", "contents": "Pharmaco-kinetics of current skeletal-seeking radiopharmaceuticals. The blood clearance of all current bone-seeking radiopharmaceuticals is biexponential during the first four hours after injection. Exponent I represents bone uptake and its clearance half-time is less than 30 min. Exponent II represents mainly urinary excretion and its clearance half-time varies from 168 to 512 min. The blood background is highest with 99mTc-labeled polyphosphate (Tc-Poly) and lowest with sodium fluoride (F-18); 99mTc-labeled diphosphonate (Tc-Dip) and 99mTc-labeled pyrophosphate (Tc-Pyro) show intermediate blood levels. The slower blood clearance of 99mTc-phosphate complexes in comparison with F-18 is due primarily to their increased protein binding. Tc-Poly blood clearance, which is slower than that of Tc-Dip and Tc-Pyro, is due primarily to its increased red cell binding and the larger size of its molecule. Bone uptake and urinary excretion of all 99mTc-labeled phosphate complexes are approximately the same: in the range of six to ten per cent in the blood, 30-33% in the urine, and 55-58 percent in the bone and other tissues. F-18 concentration in the bone is almost 1.5 times that of the 99mTc-labeled phosphate complexes. The sensitivity and resolution of lesions are identical for all 99mTc-labeled phosphate complexes and are far better than those for F-18. No toxicity is noted with the amount of phosphate present in the marketed kits, and it appears reasonable to use the minimal amount so long as efficiency is not compromised."} {"id": "PMID:175700", "title": "Effect of therapeutic irradiation on the immune responses.", "content": "The immune responses of 60 patients undergoing therapeutic irradiation were evaluated according to four anatomical sites irradiated. In vitro lymphocyte transformation tests with PHA, Con-A, and PWM and quantitative assays of IgG, IgA, and IgM were performed on blood obtained from each patient before and during therapy, and two weeks, two months, and six months after therapy. At these same testing intervals, skin tests with PPD, mumps antigen, Candida antigen, and SD-SK were performed. During irradiation, the mean values of all lymphocyte transformation tests were depressed, varying from 48% to 64% of pretreatment baseline. This depression persisted until about two months after completion of treatment. By six months, response rose to pretreatment values. When response was evaluated according to sites irradiated with all mitogens, the pelvic and pelvic plus abdominal groups showed consistently greater depression than the chest or head and neck groups. Radiation effected no significant changes in the mean values of IgG, IgA or IgM. A decrease in skin sensitivity was noted during radiation; 73% of the subjects responded positively before therapy while only 53% had at least one positive test during therapy. By two months postirradiation, 73% of the group clinically free of disease had positive skin tests. A comparison of clinical condition with test results is significant when one considers the 17 patients who developed metastatic disease or died from disease. The depression for all three mitogens during radiation therapy was greater for this group. Of the 17, only four had IgG levels in the normal range, and consistently fewer positive skin tests were demonstrated.", "contents": "Effect of therapeutic irradiation on the immune responses. The immune responses of 60 patients undergoing therapeutic irradiation were evaluated according to four anatomical sites irradiated. In vitro lymphocyte transformation tests with PHA, Con-A, and PWM and quantitative assays of IgG, IgA, and IgM were performed on blood obtained from each patient before and during therapy, and two weeks, two months, and six months after therapy. At these same testing intervals, skin tests with PPD, mumps antigen, Candida antigen, and SD-SK were performed. During irradiation, the mean values of all lymphocyte transformation tests were depressed, varying from 48% to 64% of pretreatment baseline. This depression persisted until about two months after completion of treatment. By six months, response rose to pretreatment values. When response was evaluated according to sites irradiated with all mitogens, the pelvic and pelvic plus abdominal groups showed consistently greater depression than the chest or head and neck groups. Radiation effected no significant changes in the mean values of IgG, IgA or IgM. A decrease in skin sensitivity was noted during radiation; 73% of the subjects responded positively before therapy while only 53% had at least one positive test during therapy. By two months postirradiation, 73% of the group clinically free of disease had positive skin tests. A comparison of clinical condition with test results is significant when one considers the 17 patients who developed metastatic disease or died from disease. The depression for all three mitogens during radiation therapy was greater for this group. Of the 17, only four had IgG levels in the normal range, and consistently fewer positive skin tests were demonstrated."} {"id": "PMID:175701", "title": "The spectrum of osteoblastoma.", "content": "Benign osteoblastoma is a rare tumor, more frequent in males, usually occurring in patients under the age of 30 years, and is seen most frequently in the spine, femur, tibia, and mandible. Its varied roentgenographic appearance may suggest a large osteoid osteoma or an aneurysmal bone cyst, but about one-fourth of cases present a picture consistent with a malignant neoplasm. The roentgen changes in the spine are frequently subtle and require care for identification. Differentiation from osteogenic sarcoma is sometimes difficult even with histological material, because some low grade osteogenic sarcomas contain areas resembling osteoblastoma. Conservative surgery is the treatment of choice for osteoblastoma.", "contents": "The spectrum of osteoblastoma. Benign osteoblastoma is a rare tumor, more frequent in males, usually occurring in patients under the age of 30 years, and is seen most frequently in the spine, femur, tibia, and mandible. Its varied roentgenographic appearance may suggest a large osteoid osteoma or an aneurysmal bone cyst, but about one-fourth of cases present a picture consistent with a malignant neoplasm. The roentgen changes in the spine are frequently subtle and require care for identification. Differentiation from osteogenic sarcoma is sometimes difficult even with histological material, because some low grade osteogenic sarcomas contain areas resembling osteoblastoma. Conservative surgery is the treatment of choice for osteoblastoma."} {"id": "PMID:175702", "title": "Non-rheumatic acute mitral insufficiency caused by ruptured chordae tendineae.", "content": "Five patients with proved mitral insufficiency caused by ruptured chordae tendineae were examined. Two patients came to autopsy without cardiac cateterization. Three patients, who had cardiac cateterization and surgical replacement of their mitral valves, improved dramatically. Two additional patients have been clinically diagnosed and have had corroborative cardiac catheterization and are being observed in anticipation of possible future valve replacement. Similar findings in these seven patients include adult onset of a characteristic systolic heart murmur which mimics aortic valvular stenosis, acute pulmonary edema associated with massive mitral insufficiency in the face of a normal sized or only minimally enlarged left atrium, and variable size of the left ventricle. In none of the patients were there historical or physical findings of trauma or rheumatic or bacterial endocarditis. A wide spectrum of clinical courses may be explained by the variable number of ruptured chordae tendineae at the time of clinical presentation. Although the incidence and etiology are uncertain, we believe this entity is not uncommon. Myxomatous degeneration of the connective tissue of the heart was present, but the cause remains unknown.", "contents": "Non-rheumatic acute mitral insufficiency caused by ruptured chordae tendineae. Five patients with proved mitral insufficiency caused by ruptured chordae tendineae were examined. Two patients came to autopsy without cardiac cateterization. Three patients, who had cardiac cateterization and surgical replacement of their mitral valves, improved dramatically. Two additional patients have been clinically diagnosed and have had corroborative cardiac catheterization and are being observed in anticipation of possible future valve replacement. Similar findings in these seven patients include adult onset of a characteristic systolic heart murmur which mimics aortic valvular stenosis, acute pulmonary edema associated with massive mitral insufficiency in the face of a normal sized or only minimally enlarged left atrium, and variable size of the left ventricle. In none of the patients were there historical or physical findings of trauma or rheumatic or bacterial endocarditis. A wide spectrum of clinical courses may be explained by the variable number of ruptured chordae tendineae at the time of clinical presentation. Although the incidence and etiology are uncertain, we believe this entity is not uncommon. Myxomatous degeneration of the connective tissue of the heart was present, but the cause remains unknown."} {"id": "PMID:175703", "title": "Hemochromatosis: a disease often silent but not invisible.", "content": "Hemochromatosis is a disorder characterized by the association of portal cirrhosis with deposition of excess amounts of iron in the parenchymal cells of many organs. Arthralgia and arthritis occur in about 50% of patients. The role of the radiologist is often significant in the recognition of this condition because hemochromatosis may be unsuspected clinically since the hepatic cirrhosis is frequently inactive at the time the arthritis develops. The possibility of hemochromatosis should be considered when the characteristic involvement of the metacarpophalangeal, radiocarpal, and proximal interphalangeal joints of the hand and wrist is present. In addition, articular and fibrocartilage calcification is often noted, particularly in the knee, triangular cartilage of the wrist, hip, elbow, symphysis pubis, and shoulder. Although localized chondrocalcinosis may be seen in association with many disorders, as well as in asymptomatic elderly persons, generalized chondrocalcinosis is a significant finding and is commonly associated with hemochromatosis. Recognition of the typical distribution of the arthropathy plus its characteristic roentgenographic features should aid in the identification of patients with the disorder who do not demonstrate the typical clinical features of hemochromatosis.", "contents": "Hemochromatosis: a disease often silent but not invisible. Hemochromatosis is a disorder characterized by the association of portal cirrhosis with deposition of excess amounts of iron in the parenchymal cells of many organs. Arthralgia and arthritis occur in about 50% of patients. The role of the radiologist is often significant in the recognition of this condition because hemochromatosis may be unsuspected clinically since the hepatic cirrhosis is frequently inactive at the time the arthritis develops. The possibility of hemochromatosis should be considered when the characteristic involvement of the metacarpophalangeal, radiocarpal, and proximal interphalangeal joints of the hand and wrist is present. In addition, articular and fibrocartilage calcification is often noted, particularly in the knee, triangular cartilage of the wrist, hip, elbow, symphysis pubis, and shoulder. Although localized chondrocalcinosis may be seen in association with many disorders, as well as in asymptomatic elderly persons, generalized chondrocalcinosis is a significant finding and is commonly associated with hemochromatosis. Recognition of the typical distribution of the arthropathy plus its characteristic roentgenographic features should aid in the identification of patients with the disorder who do not demonstrate the typical clinical features of hemochromatosis."} {"id": "PMID:175704", "title": "Biliary ascariasis in children.", "content": "The ascaris is a common human parasite and has a world wide distribution. In areas where it is endemic, biliary complications are common. In our locality it occurs mainly in children, presenting with upper abdominal colicky pain usually without jaundice. We have analyzed the positive roentgenological findings of 67 cases which presented in one year. The findings on cholangiography are diagnostic. The worm is seen as a linear translucent filling defect in a dilated common bile duct. Usually it is only faintly outlined by thin tram lines and occasionally there may not be excretion of the contrast material. The attention of radiologists is brought to this condition and the appearances of ascariasis infestation of the intestines are also noted.", "contents": "Biliary ascariasis in children. The ascaris is a common human parasite and has a world wide distribution. In areas where it is endemic, biliary complications are common. In our locality it occurs mainly in children, presenting with upper abdominal colicky pain usually without jaundice. We have analyzed the positive roentgenological findings of 67 cases which presented in one year. The findings on cholangiography are diagnostic. The worm is seen as a linear translucent filling defect in a dilated common bile duct. Usually it is only faintly outlined by thin tram lines and occasionally there may not be excretion of the contrast material. The attention of radiologists is brought to this condition and the appearances of ascariasis infestation of the intestines are also noted."} {"id": "PMID:175707", "title": "Roentgenology-pathology correlative study of neovascularity.", "content": "In an attempt to evaluate the histologic picture of what is shown on angiograms as neovascularity, several benign and malignant tumors were examined. New vessels (neovascularity) are large capillaries or sinusoids, and neither contain smooth muscle in their walls. The walls may contain some fibrous connective tissue. Puddling, laking, and staining represent the collection of contrast medium in small capillaries or sinusoids. Some tumors, such as hemangioma of the liver, cystadenoma of the pancreas, and angiomyolipoma of the kidney contained abnormal vascularity, but this was not composed of vessels which had arisen or developed anew, as there was smooth muscle in their walls, and this indicates that those vessels had been there from birth. In xanthogranulomatous pyelonephritis and chronic renal disease, the appearance of increased vascularity is the result of rearrangement of the normal vascular structures.", "contents": "Roentgenology-pathology correlative study of neovascularity. In an attempt to evaluate the histologic picture of what is shown on angiograms as neovascularity, several benign and malignant tumors were examined. New vessels (neovascularity) are large capillaries or sinusoids, and neither contain smooth muscle in their walls. The walls may contain some fibrous connective tissue. Puddling, laking, and staining represent the collection of contrast medium in small capillaries or sinusoids. Some tumors, such as hemangioma of the liver, cystadenoma of the pancreas, and angiomyolipoma of the kidney contained abnormal vascularity, but this was not composed of vessels which had arisen or developed anew, as there was smooth muscle in their walls, and this indicates that those vessels had been there from birth. In xanthogranulomatous pyelonephritis and chronic renal disease, the appearance of increased vascularity is the result of rearrangement of the normal vascular structures."} {"id": "PMID:175705", "title": "Intestinal malrotation in adults. Roentgenographic assessment with emphasis on isolated complete and partial nonrotations.", "content": "Intestinal malrotation may occur as an isolated deformity. It may involve either the proximal (duodenojejunal) or the distal (cecocolic) intestinal segment. A survey of 28 consecutive cases of rotational abnormalities in the adult population demonstrates a diversity of roentgenographic presentations. Twelve cases exhibited the classical form of nonrotation of the entire midgut. The rest showed isolated forms of complete and partial rotations as well as a variety of intermediary forms previously not reported in the literature. Familiarization with this concept avoids confusing interpretations and errors in the roentgenographic diagnosis.", "contents": "Intestinal malrotation in adults. Roentgenographic assessment with emphasis on isolated complete and partial nonrotations. Intestinal malrotation may occur as an isolated deformity. It may involve either the proximal (duodenojejunal) or the distal (cecocolic) intestinal segment. A survey of 28 consecutive cases of rotational abnormalities in the adult population demonstrates a diversity of roentgenographic presentations. Twelve cases exhibited the classical form of nonrotation of the entire midgut. The rest showed isolated forms of complete and partial rotations as well as a variety of intermediary forms previously not reported in the literature. Familiarization with this concept avoids confusing interpretations and errors in the roentgenographic diagnosis."} {"id": "PMID:175711", "title": "Efficacy of pneumogynecography in the diagnosis of Meyer-Rokitansky-K\u00fcster-Hauser syndrome.", "content": "Twelve patients with Meyer-Rokitansky-K\u00fcster-Hauser syndrome were examined by means of pneumogynecography. The results obtained disclose the great diagnostic value of the method in this disorder.", "contents": "Efficacy of pneumogynecography in the diagnosis of Meyer-Rokitansky-K\u00fcster-Hauser syndrome. Twelve patients with Meyer-Rokitansky-K\u00fcster-Hauser syndrome were examined by means of pneumogynecography. The results obtained disclose the great diagnostic value of the method in this disorder."} {"id": "PMID:175712", "title": "Retrocecal appendicitis presenting with air in the subhepatic space.", "content": "Two cases of perforated retrocecal appendicitis presenting with the roentgen finding of an air containing subhepatic abscess are discussed. Although it is an unusual cause for air in the right subhepatic space, retrocecal appendicitis should be considered in the radiologist's differential diagnosis.", "contents": "Retrocecal appendicitis presenting with air in the subhepatic space. Two cases of perforated retrocecal appendicitis presenting with the roentgen finding of an air containing subhepatic abscess are discussed. Although it is an unusual cause for air in the right subhepatic space, retrocecal appendicitis should be considered in the radiologist's differential diagnosis."} {"id": "PMID:175708", "title": "Complications of percutaneous transaxillary catheterization for arteriography and selective chemotherapy.", "content": "This report enumerates and analyzes the complications of percutaneous transaxillary catheterization encountered in 200 consecutive patients undergoing diagnostic arteriography, and 20 consecutive patients who had catheter placement for selective chemotherapy. Diagnostic arteriography led to minor complications in eleven percent and major complications in two percent. Risk correlated with the type of procedure, number of catheter exchanges and particularly, the presence of arteriographic risk factors, such as hypertension, bleeding tendencies, and advanced atherosclerosis. Therapeutic catheter placements had a 15 percent incidence of minor and a 20 percent incidence of major complications. Here, also, complications were more likely in the presence of the arteriographic risk factors. Suggested means for decreasing the hazards of the transaxillary catheterization include: exclusion of high risk patients, use of a proper puncture site, careful catheter manipulation, the fewest possible catheter exchanges, correct manual hemostatis following catheter withdrawal, and close observation of the patient after the procedure. Early surgical intervention is indicated in the presence of a progressively developing neural defect.", "contents": "Complications of percutaneous transaxillary catheterization for arteriography and selective chemotherapy. This report enumerates and analyzes the complications of percutaneous transaxillary catheterization encountered in 200 consecutive patients undergoing diagnostic arteriography, and 20 consecutive patients who had catheter placement for selective chemotherapy. Diagnostic arteriography led to minor complications in eleven percent and major complications in two percent. Risk correlated with the type of procedure, number of catheter exchanges and particularly, the presence of arteriographic risk factors, such as hypertension, bleeding tendencies, and advanced atherosclerosis. Therapeutic catheter placements had a 15 percent incidence of minor and a 20 percent incidence of major complications. Here, also, complications were more likely in the presence of the arteriographic risk factors. Suggested means for decreasing the hazards of the transaxillary catheterization include: exclusion of high risk patients, use of a proper puncture site, careful catheter manipulation, the fewest possible catheter exchanges, correct manual hemostatis following catheter withdrawal, and close observation of the patient after the procedure. Early surgical intervention is indicated in the presence of a progressively developing neural defect."} {"id": "PMID:175706", "title": "Arteriography of retroperitoneal lymphoma.", "content": "Arteriography was performed in 16 patients with various types of lymphoma involving the retroperitoneal space. The location and extent of the mass could be predicted in 15 cases, based upon displacement of major arteris or kidneys. Most of the studies demonstrated some degree of fine reticular neovascularity and staining within the mass; none showed extreme hypervascularity, coarse or ragged vessels, or pooling of contrast medium during the capillary phase. The differential diagnosis of lesions with this appearance includes metastases, sarcomas, neural tumors, and inflammatory masses. Arteriography may possibly prove to be of value in staging certain patients with lymphoma, although definitive assessment of its role must await further prospective studies.", "contents": "Arteriography of retroperitoneal lymphoma. Arteriography was performed in 16 patients with various types of lymphoma involving the retroperitoneal space. The location and extent of the mass could be predicted in 15 cases, based upon displacement of major arteris or kidneys. Most of the studies demonstrated some degree of fine reticular neovascularity and staining within the mass; none showed extreme hypervascularity, coarse or ragged vessels, or pooling of contrast medium during the capillary phase. The differential diagnosis of lesions with this appearance includes metastases, sarcomas, neural tumors, and inflammatory masses. Arteriography may possibly prove to be of value in staging certain patients with lymphoma, although definitive assessment of its role must await further prospective studies."} {"id": "PMID:175710", "title": "Computerized reconstructive tomography applied to breast pathology.", "content": "Breast tumors can be clearly defined from the surrounding breast parenchyma by the use of computerized reconstructive tomography. Certain types of fibrocystic mastitis also can be distinguished from tumors, but other types of fibrous mastitis and probably fibroadenomas may not be distinguishable from tumors unless contrast material is used.", "contents": "Computerized reconstructive tomography applied to breast pathology. Breast tumors can be clearly defined from the surrounding breast parenchyma by the use of computerized reconstructive tomography. Certain types of fibrocystic mastitis also can be distinguished from tumors, but other types of fibrous mastitis and probably fibroadenomas may not be distinguishable from tumors unless contrast material is used."} {"id": "PMID:175709", "title": "Analysis of cecal vasculature in the search for vascular malformations.", "content": "Four patients with gastrointestinal bleeding due to vascular malformations of the cecum are described with emphasis placed on the clinical, angiographic and pathologic features. Barium enema examinations were negative in all four cases and in three of four early venous filling identified the cecal vascular malformation. Postoperative angiographic studies of the cecal specimens using electron emission radiography were helpful in identifying these small lesions. The pathologic features and possible pathogenesis of this disorder are reviewed. Angiographic and microscopic studies in a control group of 60 post mortem and surgically extirpated cecums defined the normal circulation of the antimesenteric border. In this group, no vascular malformations were present.", "contents": "Analysis of cecal vasculature in the search for vascular malformations. Four patients with gastrointestinal bleeding due to vascular malformations of the cecum are described with emphasis placed on the clinical, angiographic and pathologic features. Barium enema examinations were negative in all four cases and in three of four early venous filling identified the cecal vascular malformation. Postoperative angiographic studies of the cecal specimens using electron emission radiography were helpful in identifying these small lesions. The pathologic features and possible pathogenesis of this disorder are reviewed. Angiographic and microscopic studies in a control group of 60 post mortem and surgically extirpated cecums defined the normal circulation of the antimesenteric border. In this group, no vascular malformations were present."} {"id": "PMID:175713", "title": "Pulmonary metastases from intracerebral meningioma. Diagnosis by percutaneous needle aspiration biopsy.", "content": "A case of metastatic meningioma to the lung is reported and the recent literature reviewed. This case was diagnosed solely by cytologic examination of fine needle aspiration biopsy. Pulmonary metastases are relatively rare and the diagnosis by this method has not previously been reported.", "contents": "Pulmonary metastases from intracerebral meningioma. Diagnosis by percutaneous needle aspiration biopsy. A case of metastatic meningioma to the lung is reported and the recent literature reviewed. This case was diagnosed solely by cytologic examination of fine needle aspiration biopsy. Pulmonary metastases are relatively rare and the diagnosis by this method has not previously been reported."} {"id": "PMID:175714", "title": "Hazards of the intensive care unit.", "content": "Complications arise in the introduction, maintenance, and use of devices for life support and monitoring in an intensive care unit. Since recognition of such complications is frequently difficult in this clinical setting, the radiologist is often in a position to be the first to detect complications associated with the use of endotracheal and tracheostomy tubes, Swan-Ganz catheters, subclavian catheters, central venous pressure catheters, and intra-aortic balloons.", "contents": "Hazards of the intensive care unit. Complications arise in the introduction, maintenance, and use of devices for life support and monitoring in an intensive care unit. Since recognition of such complications is frequently difficult in this clinical setting, the radiologist is often in a position to be the first to detect complications associated with the use of endotracheal and tracheostomy tubes, Swan-Ganz catheters, subclavian catheters, central venous pressure catheters, and intra-aortic balloons."} {"id": "PMID:175715", "title": "A device to measure roentgenographic structures.", "content": "A simple device and a nomogram are presented to permit rapid, accurate measurement of structures shown on roentgenograms. The arrangement is designed specifically for measurement of coronary vessels, but it can be adapted to other structures.", "contents": "A device to measure roentgenographic structures. A simple device and a nomogram are presented to permit rapid, accurate measurement of structures shown on roentgenograms. The arrangement is designed specifically for measurement of coronary vessels, but it can be adapted to other structures."} {"id": "PMID:175719", "title": "Villous adenomas of the colorectum.", "content": "During a ten-year period 258 patients with villous adenomas were seen at the Massachusetts General Hospital: seventy-four of these patients (29%) had invasive cancer that developed in adenomas. The operative mortality ascribed to removal of benign adenomas was zero, but for cancer arising in villous adenomas it was 3 per cent. Therapy often is difficult because of the size and location of the tumors. Methods of removal have been considered in detail.", "contents": "Villous adenomas of the colorectum. During a ten-year period 258 patients with villous adenomas were seen at the Massachusetts General Hospital: seventy-four of these patients (29%) had invasive cancer that developed in adenomas. The operative mortality ascribed to removal of benign adenomas was zero, but for cancer arising in villous adenomas it was 3 per cent. Therapy often is difficult because of the size and location of the tumors. Methods of removal have been considered in detail."} {"id": "PMID:175723", "title": "[Schnyder's corneal dystrophy and hyperlipidemia (author's transl].", "content": "Five out of ten members of a kinship were found to be affected by Schnyder's corneal dystrophy. Hyperlipoproteinemia was present in five out of eight cases examined (3 times type II, twice type IV). In one case with corneal dystrophy lipid levels were in the normal range, in another case, a child, hyperlipidemia was present without corneal abnormalities. The interrelationship of Schnyder's corneal dystrophy and disorders of lipoprotein metabolism is discussed. It is concluded that patients with Schnyder's corneal dystrophy and their relatives should be screened for hyperlipidemia; prophylactic treatment should be instituted when cases with hypercholesterinemia are found.", "contents": "[Schnyder's corneal dystrophy and hyperlipidemia (author's transl]. Five out of ten members of a kinship were found to be affected by Schnyder's corneal dystrophy. Hyperlipoproteinemia was present in five out of eight cases examined (3 times type II, twice type IV). In one case with corneal dystrophy lipid levels were in the normal range, in another case, a child, hyperlipidemia was present without corneal abnormalities. The interrelationship of Schnyder's corneal dystrophy and disorders of lipoprotein metabolism is discussed. It is concluded that patients with Schnyder's corneal dystrophy and their relatives should be screened for hyperlipidemia; prophylactic treatment should be instituted when cases with hypercholesterinemia are found."} {"id": "PMID:175724", "title": "[Ultrastructure of macular corneal dystrophy (Groenouw II): investigations of paracentral deep corneal layers (author's transl)].", "content": "Electron microscopic studies proved, that in cases of macular corneal dystrophy (Groenouw II) abnormal deposits of acid mucopolysaccharide are demonstrable in the different layers of the cornea in a polymorphic form. Because of the investigations now performed it can be established, that the opacities of the paracentral, deep corneal layers result from both dispersed vesicular and plaque-like deposits of storage material in the border area of the stroma and Descemet's membrane.", "contents": "[Ultrastructure of macular corneal dystrophy (Groenouw II): investigations of paracentral deep corneal layers (author's transl)]. Electron microscopic studies proved, that in cases of macular corneal dystrophy (Groenouw II) abnormal deposits of acid mucopolysaccharide are demonstrable in the different layers of the cornea in a polymorphic form. Because of the investigations now performed it can be established, that the opacities of the paracentral, deep corneal layers result from both dispersed vesicular and plaque-like deposits of storage material in the border area of the stroma and Descemet's membrane."} {"id": "PMID:175725", "title": "Halothane action on lymphocytes does not involve cyclic AMP.", "content": "Both theophylline and halothane inhibited transformation of human lymphocytes by phytohemagglutinin (PHA). Theophylline did not augment the inhibitory action of halothane and depressed PHA transformation of halothane-treated cells to the same extent as that of air-treated cells. Halothane- and air-treated lymphocytes, prior to PHA addition, had the same content of cyclic AMP. The addition of PHA to these cultures raised cyclic-AMP concentrations to the same extent in halothane- and air-treated lymphocytes. Halothane action on PHA-stimulated lymphocytes appears not to involve changes in cyclic nucleotide metabolism.", "contents": "Halothane action on lymphocytes does not involve cyclic AMP. Both theophylline and halothane inhibited transformation of human lymphocytes by phytohemagglutinin (PHA). Theophylline did not augment the inhibitory action of halothane and depressed PHA transformation of halothane-treated cells to the same extent as that of air-treated cells. Halothane- and air-treated lymphocytes, prior to PHA addition, had the same content of cyclic AMP. The addition of PHA to these cultures raised cyclic-AMP concentrations to the same extent in halothane- and air-treated lymphocytes. Halothane action on PHA-stimulated lymphocytes appears not to involve changes in cyclic nucleotide metabolism."} {"id": "PMID:175726", "title": "Pharmacologic modification of induced asthma.", "content": "Oral adrenergic substances (e.g., ephedrine) and phosphodiesterase inhibitors (e.g., theophylline) can have a prophylactic effect on natural or experimentally induced asthma by maintaining high levels of cyclic AMP in the target organ cells. This controlled, double-blind study evaluates these drugs alone and in a standard dosage combination in blocking asthma induced by the inhalation of pollen allergens among highly selected patients. The results support the claim that oral adrenergic drugs and xanthines can be useful in the prophylaxis of asthma.", "contents": "Pharmacologic modification of induced asthma. Oral adrenergic substances (e.g., ephedrine) and phosphodiesterase inhibitors (e.g., theophylline) can have a prophylactic effect on natural or experimentally induced asthma by maintaining high levels of cyclic AMP in the target organ cells. This controlled, double-blind study evaluates these drugs alone and in a standard dosage combination in blocking asthma induced by the inhalation of pollen allergens among highly selected patients. The results support the claim that oral adrenergic drugs and xanthines can be useful in the prophylaxis of asthma."} {"id": "PMID:175727", "title": "[Bacteriological characteristics of Streptococcus agalactiae. Incidence and conditions of appearance of the pigmentation. Sensitivity to antibiotics].", "content": "From a bacteriological study of 137 strains of streptococcus agalactiae, it seems that this species is perfectly defined by bacteriological tests, the most characteristic of which is hydrolysis with hippuric acid. The brown pigment of the strains, the conditions for demonstration of which are described and discussed here, may also be an important characteristic for it is rare in streptococci. The pigment was extracted, its nature and role are discussed. The sensitivity to 12 antibiotics was studied; the beta-lactamines were the most commonly active.", "contents": "[Bacteriological characteristics of Streptococcus agalactiae. Incidence and conditions of appearance of the pigmentation. Sensitivity to antibiotics]. From a bacteriological study of 137 strains of streptococcus agalactiae, it seems that this species is perfectly defined by bacteriological tests, the most characteristic of which is hydrolysis with hippuric acid. The brown pigment of the strains, the conditions for demonstration of which are described and discussed here, may also be an important characteristic for it is rare in streptococci. The pigment was extracted, its nature and role are discussed. The sensitivity to 12 antibiotics was studied; the beta-lactamines were the most commonly active."} {"id": "PMID:175728", "title": "[A practical method of numerical evaluation applicable to miniaturized technics of plaque assay].", "content": "When one wishes to titrate viruses by counting the number of infective foci on small surfaces of observation, one is rapidly limited by confluences which render counting impossible. Between the use of an all or nothing system which is not accurate and a total field of count, often impossible, there is an intermediate method already described and studied by Tippett, which is very little used in practice. We have performed the calculations again, drawn up reference values and given rules for choice of the field. Two examples show their practical use.", "contents": "[A practical method of numerical evaluation applicable to miniaturized technics of plaque assay]. When one wishes to titrate viruses by counting the number of infective foci on small surfaces of observation, one is rapidly limited by confluences which render counting impossible. Between the use of an all or nothing system which is not accurate and a total field of count, often impossible, there is an intermediate method already described and studied by Tippett, which is very little used in practice. We have performed the calculations again, drawn up reference values and given rules for choice of the field. Two examples show their practical use."} {"id": "PMID:175733", "title": "[The action of 2(alpha-hydroxybenzyl)-benzimidazole on 26 strains of bovine enteroviruses isolated in Algeria (author's transl)].", "content": "Bovine enteroviruses were first classified into two main groups on a serological basis. The ability to grow in the presence of 5 mug/ml of 2(alpha-hydroxybenzyl)-benzimidazole (HBB) has been reported to be characteristic of the strains belonging to group I. Twenty-six strains isolated in Algeria and previously serologically grouped were submitted to the action of GBB. The viruses of our group I (similar to La Placa's group I) exhibited the same propertie, whereas the strains of our group II were inhibited by GBB as are the strains belonging to La Placa's group II.", "contents": "[The action of 2(alpha-hydroxybenzyl)-benzimidazole on 26 strains of bovine enteroviruses isolated in Algeria (author's transl)]. Bovine enteroviruses were first classified into two main groups on a serological basis. The ability to grow in the presence of 5 mug/ml of 2(alpha-hydroxybenzyl)-benzimidazole (HBB) has been reported to be characteristic of the strains belonging to group I. Twenty-six strains isolated in Algeria and previously serologically grouped were submitted to the action of GBB. The viruses of our group I (similar to La Placa's group I) exhibited the same propertie, whereas the strains of our group II were inhibited by GBB as are the strains belonging to La Placa's group II."} {"id": "PMID:175734", "title": "A lipid and lipoprotein profile of treated and untreated diabetics.", "content": "A group of 149 diabetics and 98 healthy subjects without evidence of diabetes or ischaemic heart disease were studied. Untreated diabetics under 40 years old and 40 years of age and over showed statistically raised fasting serum turbidity, triglycerides, and raised beta and pre-beta lipoprotein levels but not raised cholesterol levels over the age and sex matched normal subjects. Further, some 63% of all diabetics showed a distinct split pre-beta lipoprotein pattern as seen on polyacrylamide disc electrolphoresis as compared with 17% in the control group. Raised lecithin and phosphatidylethanolamine (PE) levels were found in male diabetics and raised PE levels in young diabetic women. In patients under treatment with insulin, chlorpropamide, or phenformin the diabetes was well controlled in most cases, but these patients did not have significantly lower lipid levels. Diabetics on a low carbohydrate diet showed improvement in triglycerides and pre-beta lipoprotein levels, but beta lipoproteins were not lowered. It is suggested that diabetics may benefit by the inclusion of clofibrate in the treatment.", "contents": "A lipid and lipoprotein profile of treated and untreated diabetics. A group of 149 diabetics and 98 healthy subjects without evidence of diabetes or ischaemic heart disease were studied. Untreated diabetics under 40 years old and 40 years of age and over showed statistically raised fasting serum turbidity, triglycerides, and raised beta and pre-beta lipoprotein levels but not raised cholesterol levels over the age and sex matched normal subjects. Further, some 63% of all diabetics showed a distinct split pre-beta lipoprotein pattern as seen on polyacrylamide disc electrolphoresis as compared with 17% in the control group. Raised lecithin and phosphatidylethanolamine (PE) levels were found in male diabetics and raised PE levels in young diabetic women. In patients under treatment with insulin, chlorpropamide, or phenformin the diabetes was well controlled in most cases, but these patients did not have significantly lower lipid levels. Diabetics on a low carbohydrate diet showed improvement in triglycerides and pre-beta lipoprotein levels, but beta lipoproteins were not lowered. It is suggested that diabetics may benefit by the inclusion of clofibrate in the treatment."} {"id": "PMID:175735", "title": "Primary liver cancer associated with long-term oestrogen therapy.", "content": "A woman with primary liver cancer after nine years therapy with polyestradiol-phosphate is reported. The oestrogen was administered monthy by intramuscular injection for menopausal symptoms. This case suggests a possible association between long-term oestrogen therapy and the development of hepatic malignancy and also must direct attention to both hormone components in the evaluation of tumour development in users or oral contraceptives.", "contents": "Primary liver cancer associated with long-term oestrogen therapy. A woman with primary liver cancer after nine years therapy with polyestradiol-phosphate is reported. The oestrogen was administered monthy by intramuscular injection for menopausal symptoms. This case suggests a possible association between long-term oestrogen therapy and the development of hepatic malignancy and also must direct attention to both hormone components in the evaluation of tumour development in users or oral contraceptives."} {"id": "PMID:175743", "title": "Bone and kidney lesions in experimental cadmium intoxication.", "content": "Young male rats were fed a diet containing cadmium (0, 10, 30, 100, and 300 ppm) so as to morphologically investigate the relationship between bone and kidney lesions caused by experimental cadmium intoxication. In the early stage of the experiment, before the occurrence of kidney lesions, ingeted cadmium caused osteoporotic changes in bone. In later stages, slight pathologic changes in the kdidney occurred in association with urinary excretion of cadmium. However, there was no evidence of osteomalacic change in bone during the 12-week experimental period. These findings suggest that cadmium may act primarily on bone, rather than secondarily through disturbances of the kidneys, which have some protective ability against cadmium intoxication in the early stage of ingestion of the metal.", "contents": "Bone and kidney lesions in experimental cadmium intoxication. Young male rats were fed a diet containing cadmium (0, 10, 30, 100, and 300 ppm) so as to morphologically investigate the relationship between bone and kidney lesions caused by experimental cadmium intoxication. In the early stage of the experiment, before the occurrence of kidney lesions, ingeted cadmium caused osteoporotic changes in bone. In later stages, slight pathologic changes in the kdidney occurred in association with urinary excretion of cadmium. However, there was no evidence of osteomalacic change in bone during the 12-week experimental period. These findings suggest that cadmium may act primarily on bone, rather than secondarily through disturbances of the kidneys, which have some protective ability against cadmium intoxication in the early stage of ingestion of the metal."} {"id": "PMID:175748", "title": "Effect of aeration on the activity of gluconeogenetic enzymes in Saccharomyces cerevisiae growing under glucose limitation.", "content": "1. The effect of aeration on the key enzymes of gluconeogenesis was studied in baker's yeast (Saccharomyces cerevisiae) and in a nonrespiratory variant of S. cerevisiae grown under glucose limitation. 2. In baker's yeast phosphoenolpyruvate carboxykinase, hexosediphophatase and isocitrate lyase were completely repressed under anaerobic conditions. Their repression could be partially reversed by using intense aeration. 3. In the nonrespiratory variant these enzymes were absent independently of aeration. 4. Pyruvate carboxylase of baker's yeast showed maximal activity under anaerobic conditions. In the nonrespiratory variant pyruvate carboxylase had low activity under both anaerobic and aerobic conditions.", "contents": "Effect of aeration on the activity of gluconeogenetic enzymes in Saccharomyces cerevisiae growing under glucose limitation. 1. The effect of aeration on the key enzymes of gluconeogenesis was studied in baker's yeast (Saccharomyces cerevisiae) and in a nonrespiratory variant of S. cerevisiae grown under glucose limitation. 2. In baker's yeast phosphoenolpyruvate carboxykinase, hexosediphophatase and isocitrate lyase were completely repressed under anaerobic conditions. Their repression could be partially reversed by using intense aeration. 3. In the nonrespiratory variant these enzymes were absent independently of aeration. 4. Pyruvate carboxylase of baker's yeast showed maximal activity under anaerobic conditions. In the nonrespiratory variant pyruvate carboxylase had low activity under both anaerobic and aerobic conditions."} {"id": "PMID:175749", "title": "Localization of selenium in bacterial cells using TEM and energy dispersive X-Ray analysis.", "content": "Bacteria isolated from lake sediment samples reduced sodium selenite to elemental selenium. Finestructural observations were made on a number of different bacterial species cultured in the presence of sodium selenite. Examination of Escherichia coli and a Pseudomonas species revealed electron-dense deposits of irregular shape, composed of smaller units, within the cytoplasm but not on the cell wall and cell membrane. Cells of Aeromonas and Flavobacterium species exhibited conspicuous intranuclear fibrillary aggregates and different electron-dense inclusions. It appeared that the membrane structures were somewhat more easily stained in some bacterial cells after growth on agar plates containing sodium selenite. The deposits and fibrillary accumulations were interpreted to contain selenium on the basis of energy dispersive X-ray analysis. Control preparations and cells grown in the presence of sodium selenate were void of any fine-structural abnormalities. Alterations in fine structure are discussed in relation to the metabolism of selenium by bacterial cells and possible sites of inhibition.", "contents": "Localization of selenium in bacterial cells using TEM and energy dispersive X-Ray analysis. Bacteria isolated from lake sediment samples reduced sodium selenite to elemental selenium. Finestructural observations were made on a number of different bacterial species cultured in the presence of sodium selenite. Examination of Escherichia coli and a Pseudomonas species revealed electron-dense deposits of irregular shape, composed of smaller units, within the cytoplasm but not on the cell wall and cell membrane. Cells of Aeromonas and Flavobacterium species exhibited conspicuous intranuclear fibrillary aggregates and different electron-dense inclusions. It appeared that the membrane structures were somewhat more easily stained in some bacterial cells after growth on agar plates containing sodium selenite. The deposits and fibrillary accumulations were interpreted to contain selenium on the basis of energy dispersive X-ray analysis. Control preparations and cells grown in the presence of sodium selenate were void of any fine-structural abnormalities. Alterations in fine structure are discussed in relation to the metabolism of selenium by bacterial cells and possible sites of inhibition."} {"id": "PMID:175750", "title": "Microfilament bundles in antheridial nuclei of Achlya ambisexualis E 87.", "content": "This is the first report of intranuclear microfilaments within gametangial nuclei of o\u00f6mycetous fungi. Longitudinal sections of four to six microfilaments were frequently observed in meiotic antheridial nuclei of Achlya ambisexualis. Each microfilament measured approximately 7--10 nm in diameter. Spindle tubules (25 nm in diameter) were also observed within some of the nuclei possessing microfilaments.", "contents": "Microfilament bundles in antheridial nuclei of Achlya ambisexualis E 87. This is the first report of intranuclear microfilaments within gametangial nuclei of o\u00f6mycetous fungi. Longitudinal sections of four to six microfilaments were frequently observed in meiotic antheridial nuclei of Achlya ambisexualis. Each microfilament measured approximately 7--10 nm in diameter. Spindle tubules (25 nm in diameter) were also observed within some of the nuclei possessing microfilaments."} {"id": "PMID:175751", "title": "The intramitochondrial location of cytochrome c peroxidase in wild-type and petite Saccharomyces cerevisiae.", "content": "Cytochemical and ultrastructural analysis of wild-type cells of Saccharomyces cerevisiae, grown aerobically in a glucose-limited chemostat, shows that cytochrome c peroxidase is localized between the membranes of the cristae, that is, in the intracristal space. This enzyme is thus positioned appropriately within the organelle to act as an alternate terminal oxidase for the respiratory chain. The proximity of the peroxidase to major sites of generation of its two substrates may account for the small leakage of hydrogen peroxide from yeast mitochondria, as compared with the larger outflow from mammalian mitochondria. In the cytoplasmic petite mutant, gross distortion of promitochondrial membrane arrangement is evident. Nevertheless, cytochrome c perioxidase activity is present in the same amounts as is found in wild-type cells, and is localized predominantly within annuli of membrane which constitute the promitochondria in these cells. No unequivocal evidence was obtained for the localization of catalase in microbodies or other organelles in either wild-type or petite cells.", "contents": "The intramitochondrial location of cytochrome c peroxidase in wild-type and petite Saccharomyces cerevisiae. Cytochemical and ultrastructural analysis of wild-type cells of Saccharomyces cerevisiae, grown aerobically in a glucose-limited chemostat, shows that cytochrome c peroxidase is localized between the membranes of the cristae, that is, in the intracristal space. This enzyme is thus positioned appropriately within the organelle to act as an alternate terminal oxidase for the respiratory chain. The proximity of the peroxidase to major sites of generation of its two substrates may account for the small leakage of hydrogen peroxide from yeast mitochondria, as compared with the larger outflow from mammalian mitochondria. In the cytoplasmic petite mutant, gross distortion of promitochondrial membrane arrangement is evident. Nevertheless, cytochrome c perioxidase activity is present in the same amounts as is found in wild-type cells, and is localized predominantly within annuli of membrane which constitute the promitochondria in these cells. No unequivocal evidence was obtained for the localization of catalase in microbodies or other organelles in either wild-type or petite cells."} {"id": "PMID:175752", "title": "Acid phosphatase localization in the fungus Whetzelinia sclerotiorum.", "content": "Acid phosphatase was localized by light and electron microscopy in chains of vacuoles in hyphal tip cells of Whetzelinia sclerotiorum. The enzyme was present in these vacuoles whether or not conditions favored extracellular acid phosphatase secretion. Apical vesicles, microbodies, Woronin bodies, and lipid bodies did not contain acid phosphatase. The implications regarding terminology of organelles in filamentous fungi are discussed with special reference to the fungal spherosome concept.", "contents": "Acid phosphatase localization in the fungus Whetzelinia sclerotiorum. Acid phosphatase was localized by light and electron microscopy in chains of vacuoles in hyphal tip cells of Whetzelinia sclerotiorum. The enzyme was present in these vacuoles whether or not conditions favored extracellular acid phosphatase secretion. Apical vesicles, microbodies, Woronin bodies, and lipid bodies did not contain acid phosphatase. The implications regarding terminology of organelles in filamentous fungi are discussed with special reference to the fungal spherosome concept."} {"id": "PMID:175753", "title": "Effect of temperature on the viability of Bacillus stearothermophilus.", "content": "One of the obligate thermophilic bacteria, Bacillus stearothermophilus, was unable to grow at temperatures below 35 degrees C. About 80% of the population in the bacterial culture died at the temperatures, and the same extent of loss in either of the activities of oxygen consumption or synthesis of protein or nucleic acid of the organisms was observed. With the progress of death of the organisms, reduced nicotinamide-adenine dinucleotide came to be oxidized by the organisms, enzymes such as fructose-1,6-diphosphate aldolase, when the organisms were washed with phosphate buffer, were leaked out of the organisms, and an increasing amount of ribonucleoprotein was released into the culture medium. The change of the membrane state was then suggested to be one of the possible causes for the death of the organisms at the temperatures.", "contents": "Effect of temperature on the viability of Bacillus stearothermophilus. One of the obligate thermophilic bacteria, Bacillus stearothermophilus, was unable to grow at temperatures below 35 degrees C. About 80% of the population in the bacterial culture died at the temperatures, and the same extent of loss in either of the activities of oxygen consumption or synthesis of protein or nucleic acid of the organisms was observed. With the progress of death of the organisms, reduced nicotinamide-adenine dinucleotide came to be oxidized by the organisms, enzymes such as fructose-1,6-diphosphate aldolase, when the organisms were washed with phosphate buffer, were leaked out of the organisms, and an increasing amount of ribonucleoprotein was released into the culture medium. The change of the membrane state was then suggested to be one of the possible causes for the death of the organisms at the temperatures."} {"id": "PMID:175754", "title": "[Fructose 1,6-diphosphatase deficiency in 2 sisters].", "content": "The discovery of a fructose-1,6-diphosphatase deficiency in two sisters leads to the discussion of the various loading tests which are required for the diagnosis. The diagnosis may be discussed clinically with type I glycogenosis, and biologically with hereditary fructose intolerance. The specific characteristics of these disorders are analyzed as well as the problem of fructose induced hypoglucosemia. The failure of the treatment with folic acid in one of the cases leads to emphasize the suppression of prolonged fast in order to avoid acute accidents.", "contents": "[Fructose 1,6-diphosphatase deficiency in 2 sisters]. The discovery of a fructose-1,6-diphosphatase deficiency in two sisters leads to the discussion of the various loading tests which are required for the diagnosis. The diagnosis may be discussed clinically with type I glycogenosis, and biologically with hereditary fructose intolerance. The specific characteristics of these disorders are analyzed as well as the problem of fructose induced hypoglucosemia. The failure of the treatment with folic acid in one of the cases leads to emphasize the suppression of prolonged fast in order to avoid acute accidents."} {"id": "PMID:175755", "title": "[Increment in height of the upper segment and bi-iliac diameter after menarche in young girls. Longitudinal study of 40 adolescents].", "content": "The growth in height, upper segment and biiliac diameter after the menarche has been studied in 40 girls followed longitudinally until the mean age of 18 years 3 months. The mean increase in height after the menarch was 7.3 +/- 2 cm., with significant individual variations. The upper segment was responsible for much of the total increase, which was greater with an early menarche. The percentage of the final height attained by the menarche was constant: 95.5 % +/- 1,2 %. After cessation in height growth, the biiliac diameter still increased for 75 % of the children. The median value for this increase after the menarche was 2 cm., with a significant scatter. The increase in these three parameters was in indirect correlation with the bone age: the less the bone age at the menarche, the greater the increase in height, upper segment and biiliac diameter.", "contents": "[Increment in height of the upper segment and bi-iliac diameter after menarche in young girls. Longitudinal study of 40 adolescents]. The growth in height, upper segment and biiliac diameter after the menarche has been studied in 40 girls followed longitudinally until the mean age of 18 years 3 months. The mean increase in height after the menarch was 7.3 +/- 2 cm., with significant individual variations. The upper segment was responsible for much of the total increase, which was greater with an early menarche. The percentage of the final height attained by the menarche was constant: 95.5 % +/- 1,2 %. After cessation in height growth, the biiliac diameter still increased for 75 % of the children. The median value for this increase after the menarche was 2 cm., with a significant scatter. The increase in these three parameters was in indirect correlation with the bone age: the less the bone age at the menarche, the greater the increase in height, upper segment and biiliac diameter."} {"id": "PMID:175756", "title": "Fine structure of the pancreatic islets in domestic fowl with special reference to the cell type and secretion.", "content": "The pancreatic islets of domestic fowl were investigated by electron microscope. The following results were obtained. 1. The A islet is composed of a great many A cells and a few D cells. It also contained only a few B cells which are situated mainly along capillaries. 2. On the contrary, the B islet is composed of a great many B cells and a few D cells. It also contained only a few A cells in its periphary. 3. Immature secretory granules within the Golgi complex are almost the same in size, shape and density among the three types of islet cells. Since there are quite distinct differences in these properties of mature secretory granules in the cytoplasm among the three types of islet cells, there may be a difference in the mode of maturation process among the three. 4. These granules are released from the three types of islet cells through a mechanism termed as emiocytosis.", "contents": "Fine structure of the pancreatic islets in domestic fowl with special reference to the cell type and secretion. The pancreatic islets of domestic fowl were investigated by electron microscope. The following results were obtained. 1. The A islet is composed of a great many A cells and a few D cells. It also contained only a few B cells which are situated mainly along capillaries. 2. On the contrary, the B islet is composed of a great many B cells and a few D cells. It also contained only a few A cells in its periphary. 3. Immature secretory granules within the Golgi complex are almost the same in size, shape and density among the three types of islet cells. Since there are quite distinct differences in these properties of mature secretory granules in the cytoplasm among the three types of islet cells, there may be a difference in the mode of maturation process among the three. 4. These granules are released from the three types of islet cells through a mechanism termed as emiocytosis."} {"id": "PMID:175757", "title": "An ultrastructural-cytochemical study on the proliferation of smooth endoplasmic reticulum induced by chlorobiphenyls (PCB) in the guinea pig liver cells.", "content": "The ultrastructural changes in the liver cells of guinea pigs induced by the oral administration of PCB were studied by electron microscopy; also electron-microscopic cytochemistry for glucose-6-phosphatase (G-6-Pase) activity was applied. Proliferation of smooth endoplasmic reticulum (sER) was the most prominent change observed in the liver cells, which remained as long as 90 days after the final administration. G-6-Pase activity was ultracytochemically demonstrated not only in the rough and smooth endoplasmic reticulum and the nuclear envelope in the liver cells of normal controls, but also in the proliferated sER in the liver cells of PCB-treated animals. The present investigation revealed that PCB stored in the animal body induced the proliferation of sER in the liver cells for a long time after the cessation of the treatment, and that sER in the liver cells, normally existing or proliferated, always showed positive activity of G-6-Pase.", "contents": "An ultrastructural-cytochemical study on the proliferation of smooth endoplasmic reticulum induced by chlorobiphenyls (PCB) in the guinea pig liver cells. The ultrastructural changes in the liver cells of guinea pigs induced by the oral administration of PCB were studied by electron microscopy; also electron-microscopic cytochemistry for glucose-6-phosphatase (G-6-Pase) activity was applied. Proliferation of smooth endoplasmic reticulum (sER) was the most prominent change observed in the liver cells, which remained as long as 90 days after the final administration. G-6-Pase activity was ultracytochemically demonstrated not only in the rough and smooth endoplasmic reticulum and the nuclear envelope in the liver cells of normal controls, but also in the proliferated sER in the liver cells of PCB-treated animals. The present investigation revealed that PCB stored in the animal body induced the proliferation of sER in the liver cells for a long time after the cessation of the treatment, and that sER in the liver cells, normally existing or proliferated, always showed positive activity of G-6-Pase."} {"id": "PMID:175758", "title": "Frequency of genes and heredity of AK types in the Polish population.", "content": "Types of the AK groups system were determined in a sample of the Polish population numbering 660 subjects. Two phenotypes were found: AK 1-1 with a frequency of 0-933, and AK 2-1 with a frequency of 0-067. Gene frequencies were AK1 = 0-967 and AK2 = 0-033. Distribution of phenotypes in 62 families with 195 children was consistent with the hypothesis according to which heredity of AK types depends on two codominant alleles.", "contents": "Frequency of genes and heredity of AK types in the Polish population. Types of the AK groups system were determined in a sample of the Polish population numbering 660 subjects. Two phenotypes were found: AK 1-1 with a frequency of 0-933, and AK 2-1 with a frequency of 0-067. Gene frequencies were AK1 = 0-967 and AK2 = 0-033. Distribution of phenotypes in 62 families with 195 children was consistent with the hypothesis according to which heredity of AK types depends on two codominant alleles."} {"id": "PMID:175759", "title": "Changes in the heart in chronic experimental alcoholism.", "content": "In studies on the effect of chronic experimental alcoholism on the heart, rats were given 15% (v/v) solution of ethyl alcohol ad libitum instead of water to drink for 8 months. Histologic examination revealed degenerative changes in the myocardial fibers, and histochemical examination diminished activity of oxidative enzymes.", "contents": "Changes in the heart in chronic experimental alcoholism. In studies on the effect of chronic experimental alcoholism on the heart, rats were given 15% (v/v) solution of ethyl alcohol ad libitum instead of water to drink for 8 months. Histologic examination revealed degenerative changes in the myocardial fibers, and histochemical examination diminished activity of oxidative enzymes."} {"id": "PMID:175762", "title": "Calcium pyrophosphate. Histological characterization of crystals in pseudogout.", "content": "Deposits taken from an acetabulum and the head of a femur and known to contain crystals of calcium pyrophosphate were examined by selected histological methods for calcium after the application of a variety of solvents. Treatment with 10% ferric chloride removed all calcium salts tested, except a birefringent crystalline component in the pyrophosphate deposits. This corresponds to the previous optical and morphological descriptions of calcium pyrophosphate as found in synovial fluids. Calcium pyrophosphate stains consistently only by the fluorescent morin method.", "contents": "Calcium pyrophosphate. Histological characterization of crystals in pseudogout. Deposits taken from an acetabulum and the head of a femur and known to contain crystals of calcium pyrophosphate were examined by selected histological methods for calcium after the application of a variety of solvents. Treatment with 10% ferric chloride removed all calcium salts tested, except a birefringent crystalline component in the pyrophosphate deposits. This corresponds to the previous optical and morphological descriptions of calcium pyrophosphate as found in synovial fluids. Calcium pyrophosphate stains consistently only by the fluorescent morin method."} {"id": "PMID:175763", "title": "Neutrophilic leukocyte inclusions in colchicine intoxication.", "content": "Large, darkly staining, intracytoplasmic inclusions were observed in the neutrophils of a young woman after suicidal ingestion of colchicine. The polymorphonuclear neutrophils also contained intracytoplasmic and intranuclear vacuoles. Electron microscopy enabled further characterization of these morphologic changes that, although nonspecific, are consistent with certain known toxic effects of colchicine.", "contents": "Neutrophilic leukocyte inclusions in colchicine intoxication. Large, darkly staining, intracytoplasmic inclusions were observed in the neutrophils of a young woman after suicidal ingestion of colchicine. The polymorphonuclear neutrophils also contained intracytoplasmic and intranuclear vacuoles. Electron microscopy enabled further characterization of these morphologic changes that, although nonspecific, are consistent with certain known toxic effects of colchicine."} {"id": "PMID:175764", "title": "Late infantile neuronal storage disease with curvilinear bodies.", "content": "The brain and other organs of a case of late infantile neuronal storage disease were studied by light and electron microscopy. At the ultrastructural level, aggregates of typical curvilinear bodies were found in neurons and cells of every organ examined. Striking features not well documented in previously reported cases included numerous, large curvilinear bodies in proximal renal tubules and granulomas in the spleen. These findings are discussed in light of other reports of neuronal storage disease.", "contents": "Late infantile neuronal storage disease with curvilinear bodies. The brain and other organs of a case of late infantile neuronal storage disease were studied by light and electron microscopy. At the ultrastructural level, aggregates of typical curvilinear bodies were found in neurons and cells of every organ examined. Striking features not well documented in previously reported cases included numerous, large curvilinear bodies in proximal renal tubules and granulomas in the spleen. These findings are discussed in light of other reports of neuronal storage disease."} {"id": "PMID:175765", "title": "Ultrastructural alterations in livers with metastasis.", "content": "The electron microscopic examination of 13 biopsy specimens of livers that contained metastatic carcinoma revealed degenerative alterations of the mitochondria, cystic dilatation of the endoplasmic reticulum, increased amounts of osmiophilic material, some in various stages of autophagocytosis, and lipid vacuoles within the hepatocytes. In ten of 13 cases, the hepatocytes demonstrated mitochondrial paracrystalline inclusions. The observation of the latter structures in edematous hepatocytes containing phospholipid-rich osmiophilic deposits tends to confirm the experimental hypothesis that paracrystalline inclusions are caused by the precipitation of unmasked phospholipids. The spectrum of ultrastructural findings suggests hypoxia and impaired lipid metabolism of the hepatic tissue as a result of congestion and bile stasis caused by the tumor nodules.", "contents": "Ultrastructural alterations in livers with metastasis. The electron microscopic examination of 13 biopsy specimens of livers that contained metastatic carcinoma revealed degenerative alterations of the mitochondria, cystic dilatation of the endoplasmic reticulum, increased amounts of osmiophilic material, some in various stages of autophagocytosis, and lipid vacuoles within the hepatocytes. In ten of 13 cases, the hepatocytes demonstrated mitochondrial paracrystalline inclusions. The observation of the latter structures in edematous hepatocytes containing phospholipid-rich osmiophilic deposits tends to confirm the experimental hypothesis that paracrystalline inclusions are caused by the precipitation of unmasked phospholipids. The spectrum of ultrastructural findings suggests hypoxia and impaired lipid metabolism of the hepatic tissue as a result of congestion and bile stasis caused by the tumor nodules."} {"id": "PMID:175766", "title": "[Periods of spontaneous discharges in paretic muscles. Low frequency rhythms of repetitive single, grouped and serial discharges (author's transl)].", "content": "Of 1800 patients examined electromyographically, 37 showed different forms of spontaneous low frequency periodical discharges in neuromuscular diseases. Besides the well-known high frequency bizarre discharges of 10-150 per sec in neuropathies and myopathies, low frequency periods of mostly polyphasic potentials are described as \"low frequency bizarre discharge\". Three types of these rhythms are distinguished: single, grouped, and serial discharges in various peripheral nerve and motor neuron and muscle diseases. The rate of the periods varied from 0.2 to 6 per sec, but was nearly constant in one and the same muscle. The discharge rate within the period may be higher, up to 150 per sec. The low frequency single discharges probably originate in the muscle fibers, the grouped and serial discharges possibly in the terminal branches of peripheral nerves. Rhythmical repetitive discharges may result from a reduction of stimulus threshold and accommodation of muscle- and nerve fibers respectively. Grouped and serial discharges may also be provoked by nerve stimulation or voluntary innervation.", "contents": "[Periods of spontaneous discharges in paretic muscles. Low frequency rhythms of repetitive single, grouped and serial discharges (author's transl)]. Of 1800 patients examined electromyographically, 37 showed different forms of spontaneous low frequency periodical discharges in neuromuscular diseases. Besides the well-known high frequency bizarre discharges of 10-150 per sec in neuropathies and myopathies, low frequency periods of mostly polyphasic potentials are described as \"low frequency bizarre discharge\". Three types of these rhythms are distinguished: single, grouped, and serial discharges in various peripheral nerve and motor neuron and muscle diseases. The rate of the periods varied from 0.2 to 6 per sec, but was nearly constant in one and the same muscle. The discharge rate within the period may be higher, up to 150 per sec. The low frequency single discharges probably originate in the muscle fibers, the grouped and serial discharges possibly in the terminal branches of peripheral nerves. Rhythmical repetitive discharges may result from a reduction of stimulus threshold and accommodation of muscle- and nerve fibers respectively. Grouped and serial discharges may also be provoked by nerve stimulation or voluntary innervation."} {"id": "PMID:175767", "title": "The incidence of spontaneous tumors of the central nervous system of Wistar rats.", "content": "The brains of 396 old albino rats of the breed Wistar-AF/Han-EMD were examined for spontaneous tumors of the CNS and the following tumors were diagnosed: 1 oligodendroglioma, 1 astrocytoma, 1 mixed glioma, 1 pleomorphic glioma, and 19 meningiomas. Thus the CNS tumor rate was 5.8%. In addition 6 micromeningiomas were found. Knowledge of the spontaneous tumor rate including the tumor incidence in the CNS of the animal strains used for these examinations is a necessary condition for the evaluation of the results of cancerogenicity tests. CNS tumors deserve particular attention because during recent years it was found that certain chemical compounds like for instance N-methyl-N-nitrosourea induce organ-specific tumors in the brain of rats. It is recommended, therefore, to always include the central nervous system in the autopsy and histologic examination of animals from cancerogenicity trials. For cerebral autopsy transversal sections through the different cerebral regions and histologic examination of transversal section surfaces of all tumors and suspected tumor areas are suggested.", "contents": "The incidence of spontaneous tumors of the central nervous system of Wistar rats. The brains of 396 old albino rats of the breed Wistar-AF/Han-EMD were examined for spontaneous tumors of the CNS and the following tumors were diagnosed: 1 oligodendroglioma, 1 astrocytoma, 1 mixed glioma, 1 pleomorphic glioma, and 19 meningiomas. Thus the CNS tumor rate was 5.8%. In addition 6 micromeningiomas were found. Knowledge of the spontaneous tumor rate including the tumor incidence in the CNS of the animal strains used for these examinations is a necessary condition for the evaluation of the results of cancerogenicity tests. CNS tumors deserve particular attention because during recent years it was found that certain chemical compounds like for instance N-methyl-N-nitrosourea induce organ-specific tumors in the brain of rats. It is recommended, therefore, to always include the central nervous system in the autopsy and histologic examination of animals from cancerogenicity trials. For cerebral autopsy transversal sections through the different cerebral regions and histologic examination of transversal section surfaces of all tumors and suspected tumor areas are suggested."} {"id": "PMID:175768", "title": "[An electron microscopic and morphometric study of the gastric parietal cells of rats following administration of gastrin, histamine and cyclic 3',5'-adenosine monophosphate].", "content": "The ultrastructure of the gastric parietal cells was studied in rats affected by a genetic inductor of the hydrochloric acid secretion and its mediators in this process - histamine and cyclic 3', 5'-adenozinemonophosphate playing the role of the enzyme activators. All these stimulators caused similar changes in the cell structure. The square surface of the intracellular secretory tubules was shown to become 2,5 times larger, and that of the canaliculi - vesiculoid elements which seemed to be the cell membrane depot became 2,5 times less. It may be supposed that the gastric mucosa parietal cells are not the target-cells for pentagastrine (gastrine).", "contents": "[An electron microscopic and morphometric study of the gastric parietal cells of rats following administration of gastrin, histamine and cyclic 3',5'-adenosine monophosphate]. The ultrastructure of the gastric parietal cells was studied in rats affected by a genetic inductor of the hydrochloric acid secretion and its mediators in this process - histamine and cyclic 3', 5'-adenozinemonophosphate playing the role of the enzyme activators. All these stimulators caused similar changes in the cell structure. The square surface of the intracellular secretory tubules was shown to become 2,5 times larger, and that of the canaliculi - vesiculoid elements which seemed to be the cell membrane depot became 2,5 times less. It may be supposed that the gastric mucosa parietal cells are not the target-cells for pentagastrine (gastrine)."} {"id": "PMID:175769", "title": "[The specificity of intracellular changes in chick embryo blastoderm during the latent period of embryogenesis].", "content": "Yolk inclusions, lipids and polysaccharides found in the chicken embryo blastoderm cells are utilized during the latent period of embryogenesis. The yolk outside the blastoderm is not utilized. A delay in the development of the embryo of first days of incubation is related to a switching over the metabolism from utilizaiton of intracellular nutrient material to assimilation of the extracellular yolk. In the course of morphogenetical movements of the embryo, in the process of gastrulation, took place an increased biosynthesis in the blastoderm cell membranes.", "contents": "[The specificity of intracellular changes in chick embryo blastoderm during the latent period of embryogenesis]. Yolk inclusions, lipids and polysaccharides found in the chicken embryo blastoderm cells are utilized during the latent period of embryogenesis. The yolk outside the blastoderm is not utilized. A delay in the development of the embryo of first days of incubation is related to a switching over the metabolism from utilizaiton of intracellular nutrient material to assimilation of the extracellular yolk. In the course of morphogenetical movements of the embryo, in the process of gastrulation, took place an increased biosynthesis in the blastoderm cell membranes."} {"id": "PMID:175770", "title": "Adult (chronic) GM2 gangliosidosis. Atypical spinocerebellar degeneration in a Jewish sibship.", "content": "Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. Autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. Hexosaminidase A was decreased in serum and leukocytes of the living patients, and was in the range for carriers of Tay-Sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis.", "contents": "Adult (chronic) GM2 gangliosidosis. Atypical spinocerebellar degeneration in a Jewish sibship. Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. Autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. Hexosaminidase A was decreased in serum and leukocytes of the living patients, and was in the range for carriers of Tay-Sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis."} {"id": "PMID:175774", "title": "Degenerative alterations in the ventral cochlear nucleus of the guinea pig after impulse noise exposure. A preliminary light and electron microscopic study.", "content": "Guinea pigs were exposed to the noise of 40 shots of an alarm pistol held at a distance of about 60 cm. The ventral cochlear nuclei were studied in phase contrast and electron microscopy after both survival periods and longer periods of up to 55 days survival. Marked degeneration of primary cochlear nerve endings and of synapting secondary neurons of the posterior caudal part of the ventral cochlear nucleus (AVCN) and the octupus cell area (OCA) of the posterior ventral cochlear nucleus (PVCN) was found most distinctly after 5-55 days. As criteria of degeneration of the second neuron of the afferent auditory pathway we used: 1. The loss of the synapting nerve endings, mainly 'shrinking\". 2. The formation of huge mitochondria in the second order neurons and their dendrites. 3. The phagocytosis by glial cells of nerve endings, of the second order neurons and of their dendrites. After 5 days survival time no distinct changes were found in the granular cell area of PVCN, where as all stages of degeneration could be found in OCA at this time. In the discussion of these findings it is concluded that additional studies of the morphology of the cochlear nuclei seem necessary, as these may lead to a better understanding of the pathology of hearing following heavy noise exposure.", "contents": "Degenerative alterations in the ventral cochlear nucleus of the guinea pig after impulse noise exposure. A preliminary light and electron microscopic study. Guinea pigs were exposed to the noise of 40 shots of an alarm pistol held at a distance of about 60 cm. The ventral cochlear nuclei were studied in phase contrast and electron microscopy after both survival periods and longer periods of up to 55 days survival. Marked degeneration of primary cochlear nerve endings and of synapting secondary neurons of the posterior caudal part of the ventral cochlear nucleus (AVCN) and the octupus cell area (OCA) of the posterior ventral cochlear nucleus (PVCN) was found most distinctly after 5-55 days. As criteria of degeneration of the second neuron of the afferent auditory pathway we used: 1. The loss of the synapting nerve endings, mainly 'shrinking\". 2. The formation of huge mitochondria in the second order neurons and their dendrites. 3. The phagocytosis by glial cells of nerve endings, of the second order neurons and of their dendrites. After 5 days survival time no distinct changes were found in the granular cell area of PVCN, where as all stages of degeneration could be found in OCA at this time. In the discussion of these findings it is concluded that additional studies of the morphology of the cochlear nuclei seem necessary, as these may lead to a better understanding of the pathology of hearing following heavy noise exposure."} {"id": "PMID:175776", "title": "Characterization of a virus associated with epidemic conjunctivitis in Thailand.", "content": "A strain of virus, named the A-E strain, was isolated from a patient suffering from acute haemorrhagic conjunctivitis during an epidemic of the disease in Bangkok in 1972. The virus had the characteristics of an enterovirus but was not neutralized by any known enterovirus antiserum. Cross neutralization tests indicated that the isolate was closely related to the J670-71 virus isolated in Japan. The virus produced conjunctivitis in rabbits and monkeys following conjunctival inoculation.", "contents": "Characterization of a virus associated with epidemic conjunctivitis in Thailand. A strain of virus, named the A-E strain, was isolated from a patient suffering from acute haemorrhagic conjunctivitis during an epidemic of the disease in Bangkok in 1972. The virus had the characteristics of an enterovirus but was not neutralized by any known enterovirus antiserum. Cross neutralization tests indicated that the isolate was closely related to the J670-71 virus isolated in Japan. The virus produced conjunctivitis in rabbits and monkeys following conjunctival inoculation."} {"id": "PMID:175777", "title": "Reversible modification of pig heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate.", "content": "1. Pig heart mitochondrial malate dehydrogenase incubated with pyridoxal 5'-phosphate at pH 8.0 and 25 degrees C gradually loses activity. Such inactivation can be largely reversed by dialysis or by addition of L-lysine or L-cysteine, and can be made permanent by NaBH4 reduction. 2. Modification of malate dehydrogenase with pyridoxal 5'-phosphate at 35 degrees C involves two phases, an initial inactivation which is reversible and a slower irreversible second stage. 3. The initial reaction between pyridoxal 5'-phosphate and malate dehydrogenase appears to involve reversible formation of a Schiff base with the epsilon-amino group of a lysine residue. 4. Inactivation of malate dehydrogenase by pyridoxal 5'-phosphate at 10 degrees C involves only the reversible reaction. 5. At 10 degrees C repeated cycles of treatment with pyridoxal 5'-phosphate and NaBH4 reduction lead to a stepwise decline in residual activity. 6. Apparent Km values for malate and NAD+ are unaltered in the partially inactivated enzyme. 7. NAD+ and NADH give only partial protection against pyridoxal 5'-phosphate inactivation. Substrates give no effect.", "contents": "Reversible modification of pig heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate. 1. Pig heart mitochondrial malate dehydrogenase incubated with pyridoxal 5'-phosphate at pH 8.0 and 25 degrees C gradually loses activity. Such inactivation can be largely reversed by dialysis or by addition of L-lysine or L-cysteine, and can be made permanent by NaBH4 reduction. 2. Modification of malate dehydrogenase with pyridoxal 5'-phosphate at 35 degrees C involves two phases, an initial inactivation which is reversible and a slower irreversible second stage. 3. The initial reaction between pyridoxal 5'-phosphate and malate dehydrogenase appears to involve reversible formation of a Schiff base with the epsilon-amino group of a lysine residue. 4. Inactivation of malate dehydrogenase by pyridoxal 5'-phosphate at 10 degrees C involves only the reversible reaction. 5. At 10 degrees C repeated cycles of treatment with pyridoxal 5'-phosphate and NaBH4 reduction lead to a stepwise decline in residual activity. 6. Apparent Km values for malate and NAD+ are unaltered in the partially inactivated enzyme. 7. NAD+ and NADH give only partial protection against pyridoxal 5'-phosphate inactivation. Substrates give no effect."} {"id": "PMID:175779", "title": "Ontogenetic study of a myelin-derived fraction with 2':3'-cyclic nucleotide 3'-phosphodydrolase activity higher than that of myelin.", "content": "A membrane fraction (SN 4), prepared from developing and mature rat forebrain by hypo-osmotic treatment of microsome (microsomal-fraction)-free myelin, appears to be closely related to the myelin-like fraction. Fraction SN 4 shows 2':3'-cyclic nucleotide 3'-phosphohydrolase activity higher than that of the parent myelin. Electrophoresis reveals a multitude of bands with the Wolfgram protein as the main component.", "contents": "Ontogenetic study of a myelin-derived fraction with 2':3'-cyclic nucleotide 3'-phosphodydrolase activity higher than that of myelin. A membrane fraction (SN 4), prepared from developing and mature rat forebrain by hypo-osmotic treatment of microsome (microsomal-fraction)-free myelin, appears to be closely related to the myelin-like fraction. Fraction SN 4 shows 2':3'-cyclic nucleotide 3'-phosphohydrolase activity higher than that of the parent myelin. Electrophoresis reveals a multitude of bands with the Wolfgram protein as the main component."} {"id": "PMID:175778", "title": "A product-inhibition study of bovine liver glutamate dehydrogenase.", "content": "1. Initial rates of oxidative deamination of L-glutamate with NAD+ as coenzyme, and of reductive aminiation of 2-oxoglutarate with NADH as coenzyme, catalysed by bovine liver glutamate dehydrogenase were measured in 0.111 M-sodium phosphate buffer, pH 7, at 25 degrees C, in the absence and presence of product inhibitors. All 12 possible combinations of variable substrate and product inhibitor were used. 2. Strict competition was observed between NAD+ and NADH, and between glutamate and 2-oxoglutarate. All other inhibition patterns were clearly non-competitive, except for inhibition by NH4+ with NAD+ as variable substrate. Here the extrapolation did not permit a clear distinction between competitive and non-competitive inhibition. 3. Mutually non-competitive behaviour between glutamate and NH4+ indicates that these substrates can be bound at the active site simultaneously. 4. Primary Lineweaver-Burk plots and derived secondary plots of slopes and intercepts against inhibitor concentration were linear, with one exception: with 2-oxoglutarate as variable substrate, the replot of primary intercepts against inhibitory NAD+ concentration was curved. 5. Separate Ki values were evaluated for the effect of each product inhibitor on the individual terms in the reciprocal initial-rate equations. With this information it is possible to calculate rates for any combination of substrate concentrations within the experimental range with any concentration of a single product inhibitor. 6. The inhibition patterns are consistent with neither a simple compulsory-order mechanism nor a rapid-equilibrium random-order mechanism without modification. They can, however, be reconciled with either type of mechanism by postulating appropirate abortive complexes. Of the two compulsory sequences that have been proposed, one, that in which the order of binding is NADH, NH4+, 2-oxoglutarate, requires an implausible pattern of abortive complex-formation to account for the results. 7. On the basis of a rapid-equilibrium random-order mechanism, dissociation constants can be calculated from the Ki values. Where these can be compared with independent estimates from the kinetics of the uninhibited reaction or from direct measurements of substrate binding, the agreement is reasonable good. On balance, therefore, the results provide further support for the rapid-equilibrium random-order mechanism under these conditions.", "contents": "A product-inhibition study of bovine liver glutamate dehydrogenase. 1. Initial rates of oxidative deamination of L-glutamate with NAD+ as coenzyme, and of reductive aminiation of 2-oxoglutarate with NADH as coenzyme, catalysed by bovine liver glutamate dehydrogenase were measured in 0.111 M-sodium phosphate buffer, pH 7, at 25 degrees C, in the absence and presence of product inhibitors. All 12 possible combinations of variable substrate and product inhibitor were used. 2. Strict competition was observed between NAD+ and NADH, and between glutamate and 2-oxoglutarate. All other inhibition patterns were clearly non-competitive, except for inhibition by NH4+ with NAD+ as variable substrate. Here the extrapolation did not permit a clear distinction between competitive and non-competitive inhibition. 3. Mutually non-competitive behaviour between glutamate and NH4+ indicates that these substrates can be bound at the active site simultaneously. 4. Primary Lineweaver-Burk plots and derived secondary plots of slopes and intercepts against inhibitor concentration were linear, with one exception: with 2-oxoglutarate as variable substrate, the replot of primary intercepts against inhibitory NAD+ concentration was curved. 5. Separate Ki values were evaluated for the effect of each product inhibitor on the individual terms in the reciprocal initial-rate equations. With this information it is possible to calculate rates for any combination of substrate concentrations within the experimental range with any concentration of a single product inhibitor. 6. The inhibition patterns are consistent with neither a simple compulsory-order mechanism nor a rapid-equilibrium random-order mechanism without modification. They can, however, be reconciled with either type of mechanism by postulating appropirate abortive complexes. Of the two compulsory sequences that have been proposed, one, that in which the order of binding is NADH, NH4+, 2-oxoglutarate, requires an implausible pattern of abortive complex-formation to account for the results. 7. On the basis of a rapid-equilibrium random-order mechanism, dissociation constants can be calculated from the Ki values. Where these can be compared with independent estimates from the kinetics of the uninhibited reaction or from direct measurements of substrate binding, the agreement is reasonable good. On balance, therefore, the results provide further support for the rapid-equilibrium random-order mechanism under these conditions."} {"id": "PMID:175780", "title": "Dogfish M4 lactate dehydrogenase: reversible inactivation by pyridoxal 5'-phosphate and complete protection in complexes that mimic the active ternary complex.", "content": "Dogfish M4 lactate dehydrogenase, like the corresponding pig enzyme, is inactivated by pyridoxal 5'-phosphate through modification of a single essential lysine residue. The activity is completely protected in the complexes E-NAD+-oxalate, E-NADH-oxamate and E-(NAD+-pyruvate adduct), but only partially protected in E-NAD+, E-NADH, E-NAD+-oxamate and E-NADH-oxalate.", "contents": "Dogfish M4 lactate dehydrogenase: reversible inactivation by pyridoxal 5'-phosphate and complete protection in complexes that mimic the active ternary complex. Dogfish M4 lactate dehydrogenase, like the corresponding pig enzyme, is inactivated by pyridoxal 5'-phosphate through modification of a single essential lysine residue. The activity is completely protected in the complexes E-NAD+-oxalate, E-NADH-oxamate and E-(NAD+-pyruvate adduct), but only partially protected in E-NAD+, E-NADH, E-NAD+-oxamate and E-NADH-oxalate."} {"id": "PMID:175781", "title": "Evidence that phosphatidylcholine and phosphatidylethanolamine are synthesized by a single enzyme present in the endoplasmic reticulum of castor-bean endosperm.", "content": "Increasing concentrations of CDP-choline progressively inhibit the measured incorporation of CDP-[2-14C]ethanolamine into phosphatidylethanolamine catalysed by the ethanolaminephosphotransferase present in endoplasmic-reticulum membranes isolated from castor-bean endosperm cells. This inhibition parallels that observed during CDP-[Me-14C]choline incorporation and suggests that a single enzyme utilizes both these substrates.", "contents": "Evidence that phosphatidylcholine and phosphatidylethanolamine are synthesized by a single enzyme present in the endoplasmic reticulum of castor-bean endosperm. Increasing concentrations of CDP-choline progressively inhibit the measured incorporation of CDP-[2-14C]ethanolamine into phosphatidylethanolamine catalysed by the ethanolaminephosphotransferase present in endoplasmic-reticulum membranes isolated from castor-bean endosperm cells. This inhibition parallels that observed during CDP-[Me-14C]choline incorporation and suggests that a single enzyme utilizes both these substrates."} {"id": "PMID:175782", "title": "Evidence of isosteric and allosteric nucleotide inhibition of citrate synthease from multiple-inhibition studies.", "content": "Citrate synthases from diverse organisms are inhibited by ATP and NADH. Evidence is presented, from multiple-inhibition studies on various citrate synthases, that ATP acts in all cases as an isosteric inhibitor at the acetyl-CoA site. On the other hand, NADH also acts isosterically with eukaryotic and Gram-positive bacterial citrate synthases, but behaves as an allosteric inhibitor specifically in the case of the Gram-negative bacterial enzyme. After desensitization to this allosteric inhibition, only the isosteric nucleotide inhibition, as found in other citrate syntheases, is observed.", "contents": "Evidence of isosteric and allosteric nucleotide inhibition of citrate synthease from multiple-inhibition studies. Citrate synthases from diverse organisms are inhibited by ATP and NADH. Evidence is presented, from multiple-inhibition studies on various citrate synthases, that ATP acts in all cases as an isosteric inhibitor at the acetyl-CoA site. On the other hand, NADH also acts isosterically with eukaryotic and Gram-positive bacterial citrate synthases, but behaves as an allosteric inhibitor specifically in the case of the Gram-negative bacterial enzyme. After desensitization to this allosteric inhibition, only the isosteric nucleotide inhibition, as found in other citrate syntheases, is observed."} {"id": "PMID:175783", "title": "Further evidence for the concept of bovine plasma arylesterase as a lipoprotein.", "content": "Purified preparations of bovine plasma arylesterase were obtained by isoelectric focusing of enzyme prepared by (NH4)2SO4 fractionation of plasma and chromatography on DEAE-cellulose and Sephadex G-200. Although the high-density-lipoprotein fraction (HDL2) of serum provides an alternative source of enzyme, the enzymic activity of preparations made from it is much less stable. The purified arylesterase preparation has a molecular weight of 440000 and a partial specific volume of 0.91 ml/g, properties indistinguishable from those of the less highly purified enzyme. Extraction with acetone and ether removes neutral lipids from the enzyme, but the resulting lipid-depleted preparation retains most of the phospholipid present initially. A partial specific volume of 0.81 ml/g and a minimum molecular weight of approx. 100000 were determined for the lipid-depleted preparations of arylesterase. The present results support the concept of bovine plasma arylesterase as a lipoprotein in its own right, rather than as an enzymic polypeptide that is loosely associated with the HDL2 fraction of serum.", "contents": "Further evidence for the concept of bovine plasma arylesterase as a lipoprotein. Purified preparations of bovine plasma arylesterase were obtained by isoelectric focusing of enzyme prepared by (NH4)2SO4 fractionation of plasma and chromatography on DEAE-cellulose and Sephadex G-200. Although the high-density-lipoprotein fraction (HDL2) of serum provides an alternative source of enzyme, the enzymic activity of preparations made from it is much less stable. The purified arylesterase preparation has a molecular weight of 440000 and a partial specific volume of 0.91 ml/g, properties indistinguishable from those of the less highly purified enzyme. Extraction with acetone and ether removes neutral lipids from the enzyme, but the resulting lipid-depleted preparation retains most of the phospholipid present initially. A partial specific volume of 0.81 ml/g and a minimum molecular weight of approx. 100000 were determined for the lipid-depleted preparations of arylesterase. The present results support the concept of bovine plasma arylesterase as a lipoprotein in its own right, rather than as an enzymic polypeptide that is loosely associated with the HDL2 fraction of serum."} {"id": "PMID:175784", "title": "Evaluation of equilibrium constants for the interaction of lactate dehydrogenase isoenzymes with reduced nicotinamide-adenine dinucleotide by affinity chromatography.", "content": "Rabbit muscle lactate dehydrogenase was subjected to frontal affinity chromatography on Sepharose-oxamate in the presence of various concentrations of NADH and sodium phosphate buffer (0.05 M, pH 6.8) containing 0.5 M-NaCl. Quantitative interpretation of the results yields an intrinsic association constant of 9.0 x 10 (4)M-1 for the interaction of enzyme with NADH at 5 degrees C, a value that is confirmed by equilibrium-binding measurements. In a second series of experiments, zonal affinity chromatography of a mouse tissue extract under the same conditions was used to evaluate assoication constants of the order 2 x 10(5)M-1, 3 x 10(5)M-1, 4 x 10(5)M-1, 7 x 10(5)M-1 and 2 x 10(6)M-1 for the interaction of NADH with the M4, M3H, M2H2, MH3 and H4 isoenzymes respectively of lactate dehydrogenase.", "contents": "Evaluation of equilibrium constants for the interaction of lactate dehydrogenase isoenzymes with reduced nicotinamide-adenine dinucleotide by affinity chromatography. Rabbit muscle lactate dehydrogenase was subjected to frontal affinity chromatography on Sepharose-oxamate in the presence of various concentrations of NADH and sodium phosphate buffer (0.05 M, pH 6.8) containing 0.5 M-NaCl. Quantitative interpretation of the results yields an intrinsic association constant of 9.0 x 10 (4)M-1 for the interaction of enzyme with NADH at 5 degrees C, a value that is confirmed by equilibrium-binding measurements. In a second series of experiments, zonal affinity chromatography of a mouse tissue extract under the same conditions was used to evaluate assoication constants of the order 2 x 10(5)M-1, 3 x 10(5)M-1, 4 x 10(5)M-1, 7 x 10(5)M-1 and 2 x 10(6)M-1 for the interaction of NADH with the M4, M3H, M2H2, MH3 and H4 isoenzymes respectively of lactate dehydrogenase."} {"id": "PMID:175785", "title": "Purification and properties of a specific collagenase from rabbit synovial fibroblasts.", "content": "1. A specific collagenase from the culture medium of rabbit synovial fibroblasts was purified by gel filtration and ion-exchange chromatography. 2. The enzyme was homogenous on polyacrylamide-gel electrophoresis and showed only traces of contaminants when tested in gels with a non-specific antiserum. 3. The rabbit fibroblast collagenase could hydrolyse collagen both in solution and in fibrillar form. Viscometry showed that at 35 degrees C the purified enzyme could hydrolyse greater than 50 nmol of collagen/min per mg of enzyme. 4. The purified collagenase cleaved collagen in solution at either 24 degrees or 35 degrees C into the characteristic 1/4 and 3/4-length fragments. However, as compared with the impure enzyme, the purified enzyme at 35 degrees C had a much decreased capacity to further degrade the initial specific cleavage products. 5. The specific rabbit collagenase had a mol. wt. of approx. 32000 as estimated by sodium dodecyl sulphate-polyacrylamide-gel electrophoresis, and 35000 by gel filtration.", "contents": "Purification and properties of a specific collagenase from rabbit synovial fibroblasts. 1. A specific collagenase from the culture medium of rabbit synovial fibroblasts was purified by gel filtration and ion-exchange chromatography. 2. The enzyme was homogenous on polyacrylamide-gel electrophoresis and showed only traces of contaminants when tested in gels with a non-specific antiserum. 3. The rabbit fibroblast collagenase could hydrolyse collagen both in solution and in fibrillar form. Viscometry showed that at 35 degrees C the purified enzyme could hydrolyse greater than 50 nmol of collagen/min per mg of enzyme. 4. The purified collagenase cleaved collagen in solution at either 24 degrees or 35 degrees C into the characteristic 1/4 and 3/4-length fragments. However, as compared with the impure enzyme, the purified enzyme at 35 degrees C had a much decreased capacity to further degrade the initial specific cleavage products. 5. The specific rabbit collagenase had a mol. wt. of approx. 32000 as estimated by sodium dodecyl sulphate-polyacrylamide-gel electrophoresis, and 35000 by gel filtration."} {"id": "PMID:175786", "title": "Immunochemical studies with a specific antiserum to rabbit fibroblast collagenase.", "content": "1. Antisera were raised against the collagenase from rabbit synovial fibroblasts and characterized by immunoprecipitation and immunoinhibition reactions. 2. Immunoglobulins from the antisera were potent inhibitors of the action of rabbit collagenase on both reconstituted collagen fibrils and collagen in solution. 3. The antibody-binding fragment, Fab', produced by digesting the IgG (immunoglobulin G) with pepsin, inhibited collagenase activity just as well as whole IgG. 4. A specific antiserum to the rabbit collagenase was raised by a multi-step procedure. An initial antiserum was made by injecting partially purified collagenase as a complex with sheep alpha2-macroglobulin into a sheep. The non-specific antiserum so obtained was used to produce precipitin lines with the purified enzyme, and these lines were used as antigen for the production of the specific antiserum. 5. An IgG preparation from the specific antiserum was a specific and potent inhibitor of the rabbit synovial fibroblast collagenase. Neutral metallo-proteinase activity secreted by the rabbit fibroblasts was not inhibited by the antibody to the rabbit collagenase. 6. Criteria for determination of the specificity of antisera are discussed.", "contents": "Immunochemical studies with a specific antiserum to rabbit fibroblast collagenase. 1. Antisera were raised against the collagenase from rabbit synovial fibroblasts and characterized by immunoprecipitation and immunoinhibition reactions. 2. Immunoglobulins from the antisera were potent inhibitors of the action of rabbit collagenase on both reconstituted collagen fibrils and collagen in solution. 3. The antibody-binding fragment, Fab', produced by digesting the IgG (immunoglobulin G) with pepsin, inhibited collagenase activity just as well as whole IgG. 4. A specific antiserum to the rabbit collagenase was raised by a multi-step procedure. An initial antiserum was made by injecting partially purified collagenase as a complex with sheep alpha2-macroglobulin into a sheep. The non-specific antiserum so obtained was used to produce precipitin lines with the purified enzyme, and these lines were used as antigen for the production of the specific antiserum. 5. An IgG preparation from the specific antiserum was a specific and potent inhibitor of the rabbit synovial fibroblast collagenase. Neutral metallo-proteinase activity secreted by the rabbit fibroblasts was not inhibited by the antibody to the rabbit collagenase. 6. Criteria for determination of the specificity of antisera are discussed."} {"id": "PMID:175787", "title": "Synthesis of tritium-labelled isopenicillin N, penicillin N and 6-aminopenicillanic acid.", "content": "1. Phenoxymethylpenicillin sulphoxide 4-methoxybenzyl ester was labelled with 3H in its 2-beta-methyl group. Its specific radioactivity was 362 mCi/mmol. 2. Removal of the side chain of this compound yielded the corresponding ester of 6-aminopenicillanic acid sulphoxide and coupling of the latter with the appropriate protected alpha-aminoadipic acid gave 4-methoxybenzyloxycarbonylisopenicillin N sulphoxide di-4-methoxybenzyl ester or the corresponding derivative of penicillin N. 3. Removal of the protective groups by hydrogenolysis and reduction of the sulphoxide group yielded 3H-labelled isopenicillin N or penicillin N. 4. 3H-labelled phenoxymethylpenicillin sulphoxide was obtained by hydrogenolysis from its 4-methoxybenzyl ester. Reduction of its sulphoxide group and subsequent removal of the side chain gave 3H-labelled 6-aminopenicillanic acid.", "contents": "Synthesis of tritium-labelled isopenicillin N, penicillin N and 6-aminopenicillanic acid. 1. Phenoxymethylpenicillin sulphoxide 4-methoxybenzyl ester was labelled with 3H in its 2-beta-methyl group. Its specific radioactivity was 362 mCi/mmol. 2. Removal of the side chain of this compound yielded the corresponding ester of 6-aminopenicillanic acid sulphoxide and coupling of the latter with the appropriate protected alpha-aminoadipic acid gave 4-methoxybenzyloxycarbonylisopenicillin N sulphoxide di-4-methoxybenzyl ester or the corresponding derivative of penicillin N. 3. Removal of the protective groups by hydrogenolysis and reduction of the sulphoxide group yielded 3H-labelled isopenicillin N or penicillin N. 4. 3H-labelled phenoxymethylpenicillin sulphoxide was obtained by hydrogenolysis from its 4-methoxybenzyl ester. Reduction of its sulphoxide group and subsequent removal of the side chain gave 3H-labelled 6-aminopenicillanic acid."} {"id": "PMID:175788", "title": "Behaviour of tritium-labelled isopenicillin N and 6-aminopenicillanic acid as potential penicillin precursors in an extract of Penicillum chrysogenum.", "content": "1. 3H was incorporated into solvent-soluble penicillin from isopenicillin N and 6-aminopenicillanic acid 3H-labelled in the 2beta-methyl group when the labelled compounds were incubated with a crude extract of Penicillum chrysogenum. 2. With a soluble protein fraction of the extract incorporation from isopenicillin N occurred on addition of phenyl-acetyl-CoA. 3. Labelled benzylpenicillin was isolated after incubation of the crude extract with phenylacetyl-CoA and isopenicillin and the addition of unlabelled benzylpenicillin as a carrier. 4. No incorporation of 3H into solvent-soluble penicillin was detected on incubation of these extracts with penicillin N.", "contents": "Behaviour of tritium-labelled isopenicillin N and 6-aminopenicillanic acid as potential penicillin precursors in an extract of Penicillum chrysogenum. 1. 3H was incorporated into solvent-soluble penicillin from isopenicillin N and 6-aminopenicillanic acid 3H-labelled in the 2beta-methyl group when the labelled compounds were incubated with a crude extract of Penicillum chrysogenum. 2. With a soluble protein fraction of the extract incorporation from isopenicillin N occurred on addition of phenyl-acetyl-CoA. 3. Labelled benzylpenicillin was isolated after incubation of the crude extract with phenylacetyl-CoA and isopenicillin and the addition of unlabelled benzylpenicillin as a carrier. 4. No incorporation of 3H into solvent-soluble penicillin was detected on incubation of these extracts with penicillin N."} {"id": "PMID:175789", "title": "The binding of nicotinamide-adenine dimucleotide to glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus.", "content": "The binding of NAD+ to glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) from Bacillus stearothermophilus has been studied by measurement of protein fluorescence quenching. Slight negative co-operativity was observed in the binding of the third and fourth coenzyme molecules to the tetrameric enzyme. The first two coenzyme molecules were tightly bound. In this respect the enzyme resembles that from sturgeon muscle rather than that from yeast.", "contents": "The binding of nicotinamide-adenine dimucleotide to glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus. The binding of NAD+ to glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) from Bacillus stearothermophilus has been studied by measurement of protein fluorescence quenching. Slight negative co-operativity was observed in the binding of the third and fourth coenzyme molecules to the tetrameric enzyme. The first two coenzyme molecules were tightly bound. In this respect the enzyme resembles that from sturgeon muscle rather than that from yeast."} {"id": "PMID:175790", "title": "Isolation of membrane-bound renal kallikrein and kininase.", "content": "Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from homogenized rat kidney cortex. Kallikrein was concentrated in the plasma-membrane fraction, but not in the brush border of the proximal tubules. Kininase II or angiotensin I-converting enzyme was localized in the brush-border membrane. It is suggested that kallikrein in the urine may originate from the plasma membrane of the distal tubules and the conversion of angiotensin I and the inactivation of bradykinin may occur on the lumen membrane of the proximal tubular cells.", "contents": "Isolation of membrane-bound renal kallikrein and kininase. Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from homogenized rat kidney cortex. Kallikrein was concentrated in the plasma-membrane fraction, but not in the brush border of the proximal tubules. Kininase II or angiotensin I-converting enzyme was localized in the brush-border membrane. It is suggested that kallikrein in the urine may originate from the plasma membrane of the distal tubules and the conversion of angiotensin I and the inactivation of bradykinin may occur on the lumen membrane of the proximal tubular cells."} {"id": "PMID:175804", "title": "Crystal shedding and acute pseudogout. An hypothesis based on a therapeutic failure.", "content": "Four patients with chondrocalcinosis of the knees volunteered for joint lavage. Preliminary experiments indicated that disodium EDTA and magnesium ions were potent solubilizers of CPPD crystals. The procedure was a therapeutic failure in that insignificant amounts of CPPD were removed and all 4 subjects developed postlavage attacks of pseudogout. It is hypothesized that the acute attack of pseudogout is a result of crystal shedding and may be triggered by any factor that enhances CPPD solubility.", "contents": "Crystal shedding and acute pseudogout. An hypothesis based on a therapeutic failure. Four patients with chondrocalcinosis of the knees volunteered for joint lavage. Preliminary experiments indicated that disodium EDTA and magnesium ions were potent solubilizers of CPPD crystals. The procedure was a therapeutic failure in that insignificant amounts of CPPD were removed and all 4 subjects developed postlavage attacks of pseudogout. It is hypothesized that the acute attack of pseudogout is a result of crystal shedding and may be triggered by any factor that enhances CPPD solubility."} {"id": "PMID:175813", "title": "Studies on FeSV induced sarcomata in sheep with particular reference to the regional lymphatic system.", "content": "Inocula of cultured sheep cells that had been transformed with FeSV were injected into the legs of sheep so that the changes in the cellular and humoral composition of the efferent lymph from the regional node could be studied throughout the immune responses. The times at which immunoblasts and specific antibodies appeared in the lymph were similar to those recorded during responses to conventional antigens. The antiboides were mainly 7S, G1 immunoglobulins directed against virion antigens on the membranes of the transformed cells.", "contents": "Studies on FeSV induced sarcomata in sheep with particular reference to the regional lymphatic system. Inocula of cultured sheep cells that had been transformed with FeSV were injected into the legs of sheep so that the changes in the cellular and humoral composition of the efferent lymph from the regional node could be studied throughout the immune responses. The times at which immunoblasts and specific antibodies appeared in the lymph were similar to those recorded during responses to conventional antigens. The antiboides were mainly 7S, G1 immunoglobulins directed against virion antigens on the membranes of the transformed cells."} {"id": "PMID:175814", "title": "Significance of arming, potentiating and blocking factors as correlates the tumour-host interaction in the hamster SV40 system.", "content": "The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes caused significant target cell reduction. The cytotoxicity was specific as no cytotoxic effect was detected against unrelated normal as well as a malignant target cell lines. No anti-tumour effect was noted when progressor peripheral blood lymphocytes were evaluated in the Winn assay. In marked contrast, immune peripheral blood lymphocytes were capable of preventing tumour growth in the Winn assay. Furthermore, hamsters repeatedly immunized with irradiated SV40 tumour cells could resist a live cell challenge. Thus immune peripheral blood lymphocytes were chosen as the effector population to evaluate the abrogation ability of serum in the microcytotoxicity assay.", "contents": "Significance of arming, potentiating and blocking factors as correlates the tumour-host interaction in the hamster SV40 system. The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes caused significant target cell reduction. The cytotoxicity was specific as no cytotoxic effect was detected against unrelated normal as well as a malignant target cell lines. No anti-tumour effect was noted when progressor peripheral blood lymphocytes were evaluated in the Winn assay. In marked contrast, immune peripheral blood lymphocytes were capable of preventing tumour growth in the Winn assay. Furthermore, hamsters repeatedly immunized with irradiated SV40 tumour cells could resist a live cell challenge. Thus immune peripheral blood lymphocytes were chosen as the effector population to evaluate the abrogation ability of serum in the microcytotoxicity assay."} {"id": "PMID:175815", "title": "The lack of association of theta status and murine leukaemia virus content in the AKR.", "content": "Two AKR sublines appear atypical in possessing theta C3H. One of these two sublines - AKR/FuA - is notably resistant to lymphomata and is also characterized by reduced levels of the group specific murine leukaemia viral (MuLV) antigen. This suggested a possible association between theta status tumour susceptibility and viral content. Results here show no reduction in viral antigen titres in the other theta C3H tumour susceptible subline AKR/Cum, thus eliminating the possible association of theta status with the extent of MuLV replication.", "contents": "The lack of association of theta status and murine leukaemia virus content in the AKR. Two AKR sublines appear atypical in possessing theta C3H. One of these two sublines - AKR/FuA - is notably resistant to lymphomata and is also characterized by reduced levels of the group specific murine leukaemia viral (MuLV) antigen. This suggested a possible association between theta status tumour susceptibility and viral content. Results here show no reduction in viral antigen titres in the other theta C3H tumour susceptible subline AKR/Cum, thus eliminating the possible association of theta status with the extent of MuLV replication."} {"id": "PMID:175816", "title": "Cytoplasmic receptor levels and glucocorticoid response in human lymphoblastoid cell lines.", "content": "The cytolethal response to treatment with prednisolone was investigated in vitro in eight human lymphoblastoid cell lines containing varying concentrations of specific cytoplasmic glucocorticoid receptors. A similar response was observed in seven of the lines irrespective of their concentration of cytoplasmic receptors and pharmacological doses of steroid, well above those required to saturate receptors in cell-free extracts, were required for a massive lethal response. One cell line derived from Burkitt's lymphoma was refractory to lethal effects even with pharmacological doses of steroid. A similar unresponsiveness to the cytolethal effect of prednisolone in vitro was observed in fresh lymphoblasts derived from patients with acute lymphoblastic leukaemia despite evidence of a satisfactory clinical response to therapy which included steroid. The resistance of human lymphoblastoid cells to treatment with glucocorticoids in vitro may result from a defect in activation subsequent to the binding of steroid to cytoplasmic receptors.", "contents": "Cytoplasmic receptor levels and glucocorticoid response in human lymphoblastoid cell lines. The cytolethal response to treatment with prednisolone was investigated in vitro in eight human lymphoblastoid cell lines containing varying concentrations of specific cytoplasmic glucocorticoid receptors. A similar response was observed in seven of the lines irrespective of their concentration of cytoplasmic receptors and pharmacological doses of steroid, well above those required to saturate receptors in cell-free extracts, were required for a massive lethal response. One cell line derived from Burkitt's lymphoma was refractory to lethal effects even with pharmacological doses of steroid. A similar unresponsiveness to the cytolethal effect of prednisolone in vitro was observed in fresh lymphoblasts derived from patients with acute lymphoblastic leukaemia despite evidence of a satisfactory clinical response to therapy which included steroid. The resistance of human lymphoblastoid cells to treatment with glucocorticoids in vitro may result from a defect in activation subsequent to the binding of steroid to cytoplasmic receptors."} {"id": "PMID:175819", "title": "Plasma membrane associated enzymes of mammary tumours as the biochemical indicators of metastasizing capacity. Analyses of enriched plasma membrane preparations.", "content": "Plasma membranes from 6 spontaneously metastasizing and 4 non-metastasizing rat mammary carcinomata were isolated by discontinuous sucrose density gradient centrifugation of microsomal pellets. The starting microsomal fraction contained 40-50% plasma membranes as determined by the levels of 5'-nucleotidase activity, with a negligible amount of nuclear (1%), mitochondrial (5%) and lysomal (7%) contamination. Five distinct fractions (F1-F5) were banded at densities 1 X 09, 1 X 13, 1 X 15, 1 X 17 and 1 X 21 at 25 degrees C, in addition to a pellet (F6) obtained by centrifuging at 76,000 g for 17 h. The fractions F1 through F5, all contained various concentrations of membranous structures, while the pellet (F6) contained only amorphous materials as evidenced by electron microscopy. The F3 fraction at the gradient 1 X 15 had the highest specific as well as total activity of the plasma membrane marker enzyme, with aggregates of the least contaminated plasma membranes in vesicular forms. This fraction also had the lowest specific activity for glucose-6-phosphatase (smooth ER marker) and for beta-D-glucuronidase (lysomal marker), and therefore was considered to be the \"cleanest\" plasma membrane fraction. When the activity of 4 additional plasma membrane marker enzymes, i.e., alkaline phosphatase, phosphodiesterase I, nucleotide pyrophosphatase and alkaline ribonuclease was determined in the same F3 fraction, their levels were significantly lower in every metastasizing tumour than in the non-metastasizing ones, with the enzyme activity decreasing in direct proportion to the metastasizing capacity. On the other hand, the marker enzymes were high in all non-metastasizing tumours, with the activity seemingly increasing with the immunogenicity of tumour cells. There was no significant difference between the 2 groups of mammary tumours in the levels of sialic acid, hexosamine, phospholipid or cholesterol in the plasma membranes. Thus, the level of plasma membrane marker enzymes is considered an accurate indicator for metastasizing capacity in the rat mammary tumour system.", "contents": "Plasma membrane associated enzymes of mammary tumours as the biochemical indicators of metastasizing capacity. Analyses of enriched plasma membrane preparations. Plasma membranes from 6 spontaneously metastasizing and 4 non-metastasizing rat mammary carcinomata were isolated by discontinuous sucrose density gradient centrifugation of microsomal pellets. The starting microsomal fraction contained 40-50% plasma membranes as determined by the levels of 5'-nucleotidase activity, with a negligible amount of nuclear (1%), mitochondrial (5%) and lysomal (7%) contamination. Five distinct fractions (F1-F5) were banded at densities 1 X 09, 1 X 13, 1 X 15, 1 X 17 and 1 X 21 at 25 degrees C, in addition to a pellet (F6) obtained by centrifuging at 76,000 g for 17 h. The fractions F1 through F5, all contained various concentrations of membranous structures, while the pellet (F6) contained only amorphous materials as evidenced by electron microscopy. The F3 fraction at the gradient 1 X 15 had the highest specific as well as total activity of the plasma membrane marker enzyme, with aggregates of the least contaminated plasma membranes in vesicular forms. This fraction also had the lowest specific activity for glucose-6-phosphatase (smooth ER marker) and for beta-D-glucuronidase (lysomal marker), and therefore was considered to be the \"cleanest\" plasma membrane fraction. When the activity of 4 additional plasma membrane marker enzymes, i.e., alkaline phosphatase, phosphodiesterase I, nucleotide pyrophosphatase and alkaline ribonuclease was determined in the same F3 fraction, their levels were significantly lower in every metastasizing tumour than in the non-metastasizing ones, with the enzyme activity decreasing in direct proportion to the metastasizing capacity. On the other hand, the marker enzymes were high in all non-metastasizing tumours, with the activity seemingly increasing with the immunogenicity of tumour cells. There was no significant difference between the 2 groups of mammary tumours in the levels of sialic acid, hexosamine, phospholipid or cholesterol in the plasma membranes. Thus, the level of plasma membrane marker enzymes is considered an accurate indicator for metastasizing capacity in the rat mammary tumour system."} {"id": "PMID:175821", "title": "The succinic dehydrogenase and cytochrome c oxidase activities of guinea-pig skin after mild heat damage.", "content": "Succinic dehydrogenase and cytochrome c oxidase activities of guinea-pig ear skin were found to be less sensitive than oxygen uptake to mild heat damage. It therefore appears that the failure of oxygen uptake following thermal injury is not directly due to inactivation of the enzymes of the respiratory chain.", "contents": "The succinic dehydrogenase and cytochrome c oxidase activities of guinea-pig skin after mild heat damage. Succinic dehydrogenase and cytochrome c oxidase activities of guinea-pig ear skin were found to be less sensitive than oxygen uptake to mild heat damage. It therefore appears that the failure of oxygen uptake following thermal injury is not directly due to inactivation of the enzymes of the respiratory chain."} {"id": "PMID:175820", "title": "Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress.", "content": "The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10(-3) mmol g-1 body weight of adrenaline and other beta-adrenergic agonists, inflammatory agents (including local x-irradiation), convulsive seizures, \"tumbling\" or physical restraint. Lowering of innate resistance of the host to growth of seeded tumour cells induced by states of topical and systemic stress, and by the addition of an excess of lethally irradiated (LI) tumour cells to i.v. injected intact tumour cells, were all potentiated by treatment of rats with aminophylline, an inhibitor of cyclic AMP phosphodiesterase. Enhancement of tumour growth by systemic stress was inhibited by bilateral total or medullary adrenalectomy and is attributed to the release and actions of endogenous adreno-medullary hormones. Alpha-adrenergic and most non-adrenergic agents administered in maximum tolerated doses did not significantly affect host resistance to tumour growth in the lungs. These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.", "contents": "Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress. The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10(-3) mmol g-1 body weight of adrenaline and other beta-adrenergic agonists, inflammatory agents (including local x-irradiation), convulsive seizures, \"tumbling\" or physical restraint. Lowering of innate resistance of the host to growth of seeded tumour cells induced by states of topical and systemic stress, and by the addition of an excess of lethally irradiated (LI) tumour cells to i.v. injected intact tumour cells, were all potentiated by treatment of rats with aminophylline, an inhibitor of cyclic AMP phosphodiesterase. Enhancement of tumour growth by systemic stress was inhibited by bilateral total or medullary adrenalectomy and is attributed to the release and actions of endogenous adreno-medullary hormones. Alpha-adrenergic and most non-adrenergic agents administered in maximum tolerated doses did not significantly affect host resistance to tumour growth in the lungs. These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed."} {"id": "PMID:175822", "title": "Platelet dysfunction in vincristine treated patients.", "content": "Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions.", "contents": "Platelet dysfunction in vincristine treated patients. Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions."} {"id": "PMID:175823", "title": "Isolation of viral specific RNA from SV40 infected cells by viral DNA chemically linked to a cellulose matrix.", "content": "SV40 DNA fragments chemically attached to neutral cellulose powder with a water-soluble carbodiimide have been used to isolate late lytic viral specific RNA from virus infected cells. Exhaustive hybridization to SV40 DNA reveals that virtually all of the isolated RNA molecules contain SV40 specific sequences. Comparison with SV40 cRNA prepared with purified Escherichia coli RNA polymerase and a SV40 DNA I template suggests that the purity of the isolated SV40 specific RNA is very close to 100%. The background level for the nonspecific binding of RNA to a purified cellulose matrix is very low. Retention of nonspecific RNA by SV40 DNA-cellulose is only 1.5% of the viral specific RNA isolated under saturating conditions for the column. Sedimentation in neutral sucrose suggests that the major 16S viral specific RNA has been isolated largely intact.", "contents": "Isolation of viral specific RNA from SV40 infected cells by viral DNA chemically linked to a cellulose matrix. SV40 DNA fragments chemically attached to neutral cellulose powder with a water-soluble carbodiimide have been used to isolate late lytic viral specific RNA from virus infected cells. Exhaustive hybridization to SV40 DNA reveals that virtually all of the isolated RNA molecules contain SV40 specific sequences. Comparison with SV40 cRNA prepared with purified Escherichia coli RNA polymerase and a SV40 DNA I template suggests that the purity of the isolated SV40 specific RNA is very close to 100%. The background level for the nonspecific binding of RNA to a purified cellulose matrix is very low. Retention of nonspecific RNA by SV40 DNA-cellulose is only 1.5% of the viral specific RNA isolated under saturating conditions for the column. Sedimentation in neutral sucrose suggests that the major 16S viral specific RNA has been isolated largely intact."} {"id": "PMID:175824", "title": "Circular dichroism and ethidium bromide binding capacity of chromatin from cells temperature sensitive for the transformed phenotype.", "content": "Clone H6-15/163 is a clone of cells, originally derived from SV-40 transformed 3T3 cells, which express the transformed phenotype at low (32 degrees C) but not at high (39 degrees C) temperature. Chromatin was isolated from these cells grown at either temperature and studied by circular dichroism and for its ability to bind the intercalating dye, ethidium bromide. During the exponential phase of growth the chromatins of cells grown at either 32 or 39 degrees C are undistinguishable. Cessation of growth in confluent cultures results in marked changes in circular dichroism spectra and in ethidium bromide binding capacity of chromatin. The changes are much are much more pronounced at 39 degrees C (where the cells truly become quiescent) than at 32 degrees C (where cell proliferation continues although the number of cells per culture remains stationary). Temperature shifts and medium replacement also cause changes in chromatin structure, but the changes are again related to the extent of cell proliferation. It is concluded that the chromatin changes occurring in H6-15/163 cells and detectable by circular dichroism and ethidium bromide binding can be related to the proliferating activity of the cultured cells rather than to the expression of the transformed or untransformed phenotype.", "contents": "Circular dichroism and ethidium bromide binding capacity of chromatin from cells temperature sensitive for the transformed phenotype. Clone H6-15/163 is a clone of cells, originally derived from SV-40 transformed 3T3 cells, which express the transformed phenotype at low (32 degrees C) but not at high (39 degrees C) temperature. Chromatin was isolated from these cells grown at either temperature and studied by circular dichroism and for its ability to bind the intercalating dye, ethidium bromide. During the exponential phase of growth the chromatins of cells grown at either 32 or 39 degrees C are undistinguishable. Cessation of growth in confluent cultures results in marked changes in circular dichroism spectra and in ethidium bromide binding capacity of chromatin. The changes are much are much more pronounced at 39 degrees C (where the cells truly become quiescent) than at 32 degrees C (where cell proliferation continues although the number of cells per culture remains stationary). Temperature shifts and medium replacement also cause changes in chromatin structure, but the changes are again related to the extent of cell proliferation. It is concluded that the chromatin changes occurring in H6-15/163 cells and detectable by circular dichroism and ethidium bromide binding can be related to the proliferating activity of the cultured cells rather than to the expression of the transformed or untransformed phenotype."} {"id": "PMID:175825", "title": "A ribosome-independent, soluble stringent factor-like enzyme isolated from a Bacillus brevis.", "content": "A ribosome-independent synthesis of guanosine 5',3'-polyphosphates has been found in the soluble fraction of Bacillus brevis (ATCC 8185) extracts. The partially purified enzyme catalyzes the formation of both guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate, does not require 20% methanol to stimulate the rate of reaction, and is not stimulated by complexing with ribosomes of either Escherichia coli or B. brevis. The B. brevis enzyme system is not inhibited by RNase A or thiostrepton, and is only slightly inhibited by tetracycline. The pyrophosphoryl donor specificity of the B. brevis enzyme is similar to that of the E. coli ribosome-stringent factor system.", "contents": "A ribosome-independent, soluble stringent factor-like enzyme isolated from a Bacillus brevis. A ribosome-independent synthesis of guanosine 5',3'-polyphosphates has been found in the soluble fraction of Bacillus brevis (ATCC 8185) extracts. The partially purified enzyme catalyzes the formation of both guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate, does not require 20% methanol to stimulate the rate of reaction, and is not stimulated by complexing with ribosomes of either Escherichia coli or B. brevis. The B. brevis enzyme system is not inhibited by RNase A or thiostrepton, and is only slightly inhibited by tetracycline. The pyrophosphoryl donor specificity of the B. brevis enzyme is similar to that of the E. coli ribosome-stringent factor system."} {"id": "PMID:175826", "title": "A comparison of ribosomal proteins from rabbit reticulocytes phosphorylated in situ and in vitro.", "content": "A comparison has been made between the ribosomal proteins phosphorylated in intact cells and proteins isolated from ribosomal subunits after modification in vitro by purified protein kinases and [gamma-32P]ATP. When intact reticulocytes were incubated for 2 h in a nutritional medium containing radioactive inorganic phosphate, one phosphorylated protein was identified as a 40S ribosomal component using two-dimensional polyacrylamide gel electrophoresis followed by electrophoresis in a third step containing sodium dodecyl sulfate. This protein, containing 99% of the total radioactivity associated with ribosomal proteins as observed by two-dimensional electrophoresis, is found in a nonphosphorylated form in addition to several phosphorylated states. These states differ by the number of phosphoryl group attached to the protein. The same 40S protein is modified in vitro by the three cAMP-regulated protein kinases from rabbit reticulocytes. Two additional proteins associated with the 40S subunit are phosphorylated in situ. These proteins migrate as a symmetrical doublet, and contain less than 1% of the radioactive phosphate in the 40S subunit. A number of phosphorylated proteins associated with 60S subunits are observed by disc gel electrophoresis after incubation of whole cells with labeled phosphate. These proteins do not migrate with previously identified ribosomal proteins and are not present in sufficient amounts to be identified as ribosomal structural proteins. Proteins in the large subunit are modified in vitro by cAMP-regulated protein kinases and ATP, and these modified proteins migrate with known ribosomal proteins. However, this phosphorylation has not been shown to occur in intact cells.", "contents": "A comparison of ribosomal proteins from rabbit reticulocytes phosphorylated in situ and in vitro. A comparison has been made between the ribosomal proteins phosphorylated in intact cells and proteins isolated from ribosomal subunits after modification in vitro by purified protein kinases and [gamma-32P]ATP. When intact reticulocytes were incubated for 2 h in a nutritional medium containing radioactive inorganic phosphate, one phosphorylated protein was identified as a 40S ribosomal component using two-dimensional polyacrylamide gel electrophoresis followed by electrophoresis in a third step containing sodium dodecyl sulfate. This protein, containing 99% of the total radioactivity associated with ribosomal proteins as observed by two-dimensional electrophoresis, is found in a nonphosphorylated form in addition to several phosphorylated states. These states differ by the number of phosphoryl group attached to the protein. The same 40S protein is modified in vitro by the three cAMP-regulated protein kinases from rabbit reticulocytes. Two additional proteins associated with the 40S subunit are phosphorylated in situ. These proteins migrate as a symmetrical doublet, and contain less than 1% of the radioactive phosphate in the 40S subunit. A number of phosphorylated proteins associated with 60S subunits are observed by disc gel electrophoresis after incubation of whole cells with labeled phosphate. These proteins do not migrate with previously identified ribosomal proteins and are not present in sufficient amounts to be identified as ribosomal structural proteins. Proteins in the large subunit are modified in vitro by cAMP-regulated protein kinases and ATP, and these modified proteins migrate with known ribosomal proteins. However, this phosphorylation has not been shown to occur in intact cells."} {"id": "PMID:175827", "title": "The oxidation of phenylhydrazine: superoxide and mechanism.", "content": "The oxidation of phenylhydrazine in buffered aqueous solutions is a complex process involving several intermediates. It can be initiated by metal cations, such as Cu2+; in which case EDTA acts as an inhibitor. It can also be intiated by oxyhemoglobin; in which case chelating agents do not interfere. Superoxide radical is both a product of this reaction and a chain propagator. The formation of O2- could be demonstrated in terms of a reduction of nitroblue tetrazolium, which was prevented by superoxide dismutase. The importance of O2- in carrying the reaction chains was shown by the inhibition of phenylhydrazine oxidation by superoxide dismutase. Hydrogen peroxide accumulated during the reaction and could be detected with catalase. The progress of this oxidation could be monitored in terms of oxygen consumption and by following increases in absorbance at 280 or 320 nm. The oxidation was markedly autocatalytic and superoxide dismutase had the effect of extending the lag period. The absorbance at 280 nm was due to an intermediate which first accumulated and was then consumed. This intermediate appears to be benzendiazonium ion. The absorbance at 320 nm was due to a stable product, which was not identified. The time course of oxygen consumption paralleled the increase in absorbance at 320 nm and lagged behind the changes at 280 nm. Exogenous benzenediazonium ion accelerated the oxidation of phenylhydrazine and eliminated the lag phase. Benzenediazonium ion must therefore react with phenylhydrazine to produce a very reactive intermediate, possibly phenyldiazene. A mechanism was proposed which is consistent with the data. The intermediates and products of the oxidation of phenylhydrazine include superoxide radical, hydrogen peroxide, phenylhydrazyl radical, phenyldiazene, and benzenediazonium ion. This is a minimal list: others remain to be detected and identified. It appears likely that the diverse biological effects of phenylhydrazine are largely due to the reactivities of these intermediates and products.", "contents": "The oxidation of phenylhydrazine: superoxide and mechanism. The oxidation of phenylhydrazine in buffered aqueous solutions is a complex process involving several intermediates. It can be initiated by metal cations, such as Cu2+; in which case EDTA acts as an inhibitor. It can also be intiated by oxyhemoglobin; in which case chelating agents do not interfere. Superoxide radical is both a product of this reaction and a chain propagator. The formation of O2- could be demonstrated in terms of a reduction of nitroblue tetrazolium, which was prevented by superoxide dismutase. The importance of O2- in carrying the reaction chains was shown by the inhibition of phenylhydrazine oxidation by superoxide dismutase. Hydrogen peroxide accumulated during the reaction and could be detected with catalase. The progress of this oxidation could be monitored in terms of oxygen consumption and by following increases in absorbance at 280 or 320 nm. The oxidation was markedly autocatalytic and superoxide dismutase had the effect of extending the lag period. The absorbance at 280 nm was due to an intermediate which first accumulated and was then consumed. This intermediate appears to be benzendiazonium ion. The absorbance at 320 nm was due to a stable product, which was not identified. The time course of oxygen consumption paralleled the increase in absorbance at 320 nm and lagged behind the changes at 280 nm. Exogenous benzenediazonium ion accelerated the oxidation of phenylhydrazine and eliminated the lag phase. Benzenediazonium ion must therefore react with phenylhydrazine to produce a very reactive intermediate, possibly phenyldiazene. A mechanism was proposed which is consistent with the data. The intermediates and products of the oxidation of phenylhydrazine include superoxide radical, hydrogen peroxide, phenylhydrazyl radical, phenyldiazene, and benzenediazonium ion. This is a minimal list: others remain to be detected and identified. It appears likely that the diverse biological effects of phenylhydrazine are largely due to the reactivities of these intermediates and products."} {"id": "PMID:175828", "title": "Iodination of DNA. Studies of the reaction and iodination of papovavirus DNA.", "content": "Iodination of DNA by the reaction originally described by S. L. Commerford ((1971), Biochemistry 10, 1993) is extremely sensitive to the secondary structure of the DNA. Cytidines in denatured simian virus 40 (SV40) DNA react at a slightly slower rate than free cytidine monophosphate; hydrogen-bonded cytidines in SV40 form I DNA are iodinated considerably more slowly; elimination of the negative supercoils in form I DNA by conversion to form II or form III reduces reactivity even further. The residual reactivity of form II or form III duplex DNA is not due to preferential iodination of unpaired cytidines near phosphodiester bond breaks; rather iodination occurs throughout the molecule. Cytidine monophosphate has been used as a model for DNA, to enable spectral measurements of its reaction with iodine and T1C13. At temperatures above 42 degrees C and at pH 5.0, formation of 5-iodocytidine is limited by the rate of formation of an intermediate, probably 5-iodo-6-hydroxydihydrocytidine. At lower temperatures, the conversion of intermediate to product is rate limiting, but can be accelerated by lowering the pH. By appropriate adjustment of pH, or temperature, the formation of intermediate or its conversion to product can be accelerated. Iodination destabilizes the DNA duplex. Iodocytosines in SV40 DNA are preferentially removed by S1 nuclease. Heavily iodinated DNA does not reassociate normally, but DNA with only 5-10% of its cytosines iodinated appears to reassociate with normal kinetics, if duplex formation is measured by hydroxylapatite chromatography. Conditions are described to permit preparation of DNA, which reassociates normally, having a specific activity of 10(8) cpm/mug.", "contents": "Iodination of DNA. Studies of the reaction and iodination of papovavirus DNA. Iodination of DNA by the reaction originally described by S. L. Commerford ((1971), Biochemistry 10, 1993) is extremely sensitive to the secondary structure of the DNA. Cytidines in denatured simian virus 40 (SV40) DNA react at a slightly slower rate than free cytidine monophosphate; hydrogen-bonded cytidines in SV40 form I DNA are iodinated considerably more slowly; elimination of the negative supercoils in form I DNA by conversion to form II or form III reduces reactivity even further. The residual reactivity of form II or form III duplex DNA is not due to preferential iodination of unpaired cytidines near phosphodiester bond breaks; rather iodination occurs throughout the molecule. Cytidine monophosphate has been used as a model for DNA, to enable spectral measurements of its reaction with iodine and T1C13. At temperatures above 42 degrees C and at pH 5.0, formation of 5-iodocytidine is limited by the rate of formation of an intermediate, probably 5-iodo-6-hydroxydihydrocytidine. At lower temperatures, the conversion of intermediate to product is rate limiting, but can be accelerated by lowering the pH. By appropriate adjustment of pH, or temperature, the formation of intermediate or its conversion to product can be accelerated. Iodination destabilizes the DNA duplex. Iodocytosines in SV40 DNA are preferentially removed by S1 nuclease. Heavily iodinated DNA does not reassociate normally, but DNA with only 5-10% of its cytosines iodinated appears to reassociate with normal kinetics, if duplex formation is measured by hydroxylapatite chromatography. Conditions are described to permit preparation of DNA, which reassociates normally, having a specific activity of 10(8) cpm/mug."} {"id": "PMID:175829", "title": "Prenyltransferase: the mechanism of the reaction.", "content": "The enzyme, prenyltransferase, which normally catalyzes the addition of an allylic pyrophosphate to isopentenyl pyrophosphate, has been found to catalyze the hydrolysis of its allylic substrate. The rate of this hydrolysis is markedly stimulated by inorganic pyrophosphate. Competition experiments with 2-fluoroisopentenyl pyrophosphate and inorganic pyrophosphate demonstrated that inorganic pyrophosphate stimulated hydrolysis by binding at the isopentenyl pyrophosphate site. Hydrolysis carried out in H218O or with (1S)-[1-3H]geranyl pyrophosphate show the C-O bond is broken and the C1 carbon of geranyl pyrophosphate is inverted in the process. These results are interpreted to favor a carbonium ion mechanism for the prenyltransferase reaction.", "contents": "Prenyltransferase: the mechanism of the reaction. The enzyme, prenyltransferase, which normally catalyzes the addition of an allylic pyrophosphate to isopentenyl pyrophosphate, has been found to catalyze the hydrolysis of its allylic substrate. The rate of this hydrolysis is markedly stimulated by inorganic pyrophosphate. Competition experiments with 2-fluoroisopentenyl pyrophosphate and inorganic pyrophosphate demonstrated that inorganic pyrophosphate stimulated hydrolysis by binding at the isopentenyl pyrophosphate site. Hydrolysis carried out in H218O or with (1S)-[1-3H]geranyl pyrophosphate show the C-O bond is broken and the C1 carbon of geranyl pyrophosphate is inverted in the process. These results are interpreted to favor a carbonium ion mechanism for the prenyltransferase reaction."} {"id": "PMID:175830", "title": "Subunit structure of human erythrocyte glycophorin A.", "content": "Glycophorin A is a sialoglycoprotein isolated from human erythrocyte membranes which seems to exist as stable dimeric complexes in the presence of sodium dodecyl sulfate. When analyzed by dodecyl sulfate acrylamide electrophoresis this molecule forms two PAS-stainable bands (PAS-U and PAS-2) which are reversibly interconvertible. This change in electrophoretic mobility is dependent on the concentration of dodecyl sulfate, the use of Trisbuffer systems, the protein concentration in the incubation mixture, and the duration and temperature of incubation before electrophoresis. Reducing agents do no influence the results. Chromatography of the sialoglycopeptides on Sepharose columns in dodecyl sulfate before and after heat treatment gave similar results. A small hydrophobic peptide (T-6) derived from glycophorin A was able to prevent reassociation of the monomeric subunits back to the higher molecular weight form. This peptide was able to bind to the subunit of glycophorin A, but not to the high molecular weight complex. These results are consistent with a model of glycophorin A composed of two subunits which can dissociate and reassociate in the presence of detergents. These subunits may interact via the hydrophobic portions of the polypeptide chains.", "contents": "Subunit structure of human erythrocyte glycophorin A. Glycophorin A is a sialoglycoprotein isolated from human erythrocyte membranes which seems to exist as stable dimeric complexes in the presence of sodium dodecyl sulfate. When analyzed by dodecyl sulfate acrylamide electrophoresis this molecule forms two PAS-stainable bands (PAS-U and PAS-2) which are reversibly interconvertible. This change in electrophoretic mobility is dependent on the concentration of dodecyl sulfate, the use of Trisbuffer systems, the protein concentration in the incubation mixture, and the duration and temperature of incubation before electrophoresis. Reducing agents do no influence the results. Chromatography of the sialoglycopeptides on Sepharose columns in dodecyl sulfate before and after heat treatment gave similar results. A small hydrophobic peptide (T-6) derived from glycophorin A was able to prevent reassociation of the monomeric subunits back to the higher molecular weight form. This peptide was able to bind to the subunit of glycophorin A, but not to the high molecular weight complex. These results are consistent with a model of glycophorin A composed of two subunits which can dissociate and reassociate in the presence of detergents. These subunits may interact via the hydrophobic portions of the polypeptide chains."} {"id": "PMID:175831", "title": "Studies on human serum high-density lipoproteins. Self-association of human serum apolipoprotein A-II in aqueous solutions.", "content": "Some of the solution properties of pure preparations of human serum high-density apolipoprotein A-II were studied by sedimentation equilibrium ultracentrifugation, conducted at different apoprotein concentrations and at several speeds. The concentration dependence of the apparent weight average molecular weight indicated that apolipoprotein A-II, when dissolved in 0.02 MEDTA (pH 8.6), undergoes self-association. Over a protein concentration range between 0.8 and 1.5 mg/ml, the self-association could best be described by a monomer-dimer-trimer step association, although indefinite self-association could not be ruled out. The equilibrium constants obtained were sufficient to describe the system over the concentration range investigated.", "contents": "Studies on human serum high-density lipoproteins. Self-association of human serum apolipoprotein A-II in aqueous solutions. Some of the solution properties of pure preparations of human serum high-density apolipoprotein A-II were studied by sedimentation equilibrium ultracentrifugation, conducted at different apoprotein concentrations and at several speeds. The concentration dependence of the apparent weight average molecular weight indicated that apolipoprotein A-II, when dissolved in 0.02 MEDTA (pH 8.6), undergoes self-association. Over a protein concentration range between 0.8 and 1.5 mg/ml, the self-association could best be described by a monomer-dimer-trimer step association, although indefinite self-association could not be ruled out. The equilibrium constants obtained were sufficient to describe the system over the concentration range investigated."} {"id": "PMID:175832", "title": "Phosphatidylglycerol biosynthesis in Bacillus licheniformis Resolution of membrane-bound enzymes by affinity chromatography on cytidinediphospho-sn-1,2-diacylglycerol Sepharose.", "content": "Cytidinediphospho-sn-1,2-diaclglycerol (CDP-diglyceride) has been covalently linked to Sephrose 4B via adipic acid dihydrazide spacer arm forming an effective affinity chromatography column. This liponucleo-tide ligand and sn-glycero-3-phosphate are subtracts for the formation of 3-sn-phoshatidyl-1'-sn-glycero-3'-phosphate (PGP) catalyzed in both eukaryotic and prokaryotic organisms by sn-glycero-3-phosphate: CMP phosphatidlytranferase (PGP synthetase). Using this CDP-diglyceride Sephrose affinity column we were able to resolve the membrane associated 3-sn-phosphatidyl'1-sn-glycerol (PG) synthesizing system present in Bacillus licheniformis into two activities. A PGP synthetase activity was adsorbed to the affinity column and was eluted using buffer containg CDP-diglyceride; a PGP phosphatease acactivity had no affinity for the column. Both PGP synthase and PGP phosphatase of B. licheniformis were associated with a membrane component of the cell as evidenced by sucrose gradient centrifugation, differential centrifugation, and solubilization by buffers containing detergent...", "contents": "Phosphatidylglycerol biosynthesis in Bacillus licheniformis Resolution of membrane-bound enzymes by affinity chromatography on cytidinediphospho-sn-1,2-diacylglycerol Sepharose. Cytidinediphospho-sn-1,2-diaclglycerol (CDP-diglyceride) has been covalently linked to Sephrose 4B via adipic acid dihydrazide spacer arm forming an effective affinity chromatography column. This liponucleo-tide ligand and sn-glycero-3-phosphate are subtracts for the formation of 3-sn-phoshatidyl-1'-sn-glycero-3'-phosphate (PGP) catalyzed in both eukaryotic and prokaryotic organisms by sn-glycero-3-phosphate: CMP phosphatidlytranferase (PGP synthetase). Using this CDP-diglyceride Sephrose affinity column we were able to resolve the membrane associated 3-sn-phosphatidyl'1-sn-glycerol (PG) synthesizing system present in Bacillus licheniformis into two activities. A PGP synthetase activity was adsorbed to the affinity column and was eluted using buffer containg CDP-diglyceride; a PGP phosphatease acactivity had no affinity for the column. Both PGP synthase and PGP phosphatase of B. licheniformis were associated with a membrane component of the cell as evidenced by sucrose gradient centrifugation, differential centrifugation, and solubilization by buffers containing detergent..."} {"id": "PMID:175833", "title": "Multiple forms of oviduct progesterone receptors analyzed by ion exchange filtration and gel electrophoresis.", "content": "Resolution of the multiple forms of steroid receptors in small samples has been improved by two new techniques: preparative ion exchange filtration and electrophoresis in highly cross-linked polyacrylamide gels of varied concentration. These techniques were used in conjunction with protamine precipitation, gel filtration, and density gradient centrifugation to separate five forms of the progesterone receptor of chick oviduct cytosol. These complexes, numbered I to V in order of elution from agarose gel columns, have been characterized with respect to apparent molecular weight, shape, and relative net charge. Form I, which is eluted in the void volume after gel filtration of cytosol in hypotonic media, is heterodisperse with respect to sedimentation coefficient and electrophoretic mobility (Rf). Form I is converted to form III by KC1. Form II has the highest axial ratio and the highest Rf at pH 10.2. This 4.2S complex can be extracted from DEAE filters, but not from protamine-precipitated cytosol, by 0.3 to 0.5 M KC1. Form III is slightly smaller (3.9S) and less asymmetric than form II. It is relased from DEAE filters and protamine-precipitated cytosol by 0.15 M KC1 and displays increased Rf upon purification. Forms II and III correspond to the B and A components described by W. T. Schrader and B. W. O'Malley ((1972), J. Biol. Chem 247, 51). Form IV may result from the proteolytic cleavage of forms II and/or III. Form V is a globular polypeptide obtained in the presence of certain divalent cations. This complex has been named the \"mero-receptor\" since it is the smallest part or fragment of the receptor that contains the steroid-binding site.", "contents": "Multiple forms of oviduct progesterone receptors analyzed by ion exchange filtration and gel electrophoresis. Resolution of the multiple forms of steroid receptors in small samples has been improved by two new techniques: preparative ion exchange filtration and electrophoresis in highly cross-linked polyacrylamide gels of varied concentration. These techniques were used in conjunction with protamine precipitation, gel filtration, and density gradient centrifugation to separate five forms of the progesterone receptor of chick oviduct cytosol. These complexes, numbered I to V in order of elution from agarose gel columns, have been characterized with respect to apparent molecular weight, shape, and relative net charge. Form I, which is eluted in the void volume after gel filtration of cytosol in hypotonic media, is heterodisperse with respect to sedimentation coefficient and electrophoretic mobility (Rf). Form I is converted to form III by KC1. Form II has the highest axial ratio and the highest Rf at pH 10.2. This 4.2S complex can be extracted from DEAE filters, but not from protamine-precipitated cytosol, by 0.3 to 0.5 M KC1. Form III is slightly smaller (3.9S) and less asymmetric than form II. It is relased from DEAE filters and protamine-precipitated cytosol by 0.15 M KC1 and displays increased Rf upon purification. Forms II and III correspond to the B and A components described by W. T. Schrader and B. W. O'Malley ((1972), J. Biol. Chem 247, 51). Form IV may result from the proteolytic cleavage of forms II and/or III. Form V is a globular polypeptide obtained in the presence of certain divalent cations. This complex has been named the \"mero-receptor\" since it is the smallest part or fragment of the receptor that contains the steroid-binding site."} {"id": "PMID:175834", "title": "Changes in poly(adenosine diphosphate-ribose) and poly(adenosine diphosphate-ribose) polymerase in synchronous HeLa cells.", "content": "An antibody has been prepared which is highly specific for poly(adenosine diphosphate-ribose). Neither poly(A), DNA, nor a variety of adenine-containing nucleosides or nucleotides were effective in competing with poly(ADP-ribose) for binding to the antibody. Of all compounds tested, only adenosine diphosphate-ribose competed for binding to the antibody. Unlabeled poly(adenosine diphosphate-ribose) was about 10 000 times more effective in competing with labeled polymer for antibody binding than was adenosine diphosphate-ribose. Using the antibody, the amount of poly(adenosine diphosphate-ribose) was found to increase from early S phase to a peak at mid S with a second, even larger increase seen at the S-G2 transition point in synchronously dividing HeLa cells. Pulse labeling of the polymer with [2-3H]adenosine was also maximal at the same time points. Changes in the levels of poly(adenosine diphosphate-ribose) polymerase activity measured in isolated nuclei coincided with the changes in amounts of polymer present in intact cells during progression from S phase into G2.", "contents": "Changes in poly(adenosine diphosphate-ribose) and poly(adenosine diphosphate-ribose) polymerase in synchronous HeLa cells. An antibody has been prepared which is highly specific for poly(adenosine diphosphate-ribose). Neither poly(A), DNA, nor a variety of adenine-containing nucleosides or nucleotides were effective in competing with poly(ADP-ribose) for binding to the antibody. Of all compounds tested, only adenosine diphosphate-ribose competed for binding to the antibody. Unlabeled poly(adenosine diphosphate-ribose) was about 10 000 times more effective in competing with labeled polymer for antibody binding than was adenosine diphosphate-ribose. Using the antibody, the amount of poly(adenosine diphosphate-ribose) was found to increase from early S phase to a peak at mid S with a second, even larger increase seen at the S-G2 transition point in synchronously dividing HeLa cells. Pulse labeling of the polymer with [2-3H]adenosine was also maximal at the same time points. Changes in the levels of poly(adenosine diphosphate-ribose) polymerase activity measured in isolated nuclei coincided with the changes in amounts of polymer present in intact cells during progression from S phase into G2."} {"id": "PMID:175835", "title": "Burkitt's lymphoma - a human tumor model system for immunological studies.", "content": "Burkitt's lymphoma occurs mainly in parts of tropical Africa and has attracted the attention of experimental workers due to its epidemiological and clinical features, which indicate a viral etiology and a host immune response to the tumor. As a result of virological studies, Epstein-Barr virus (EBV) DNA has been demonstrated in almost all tested biopsies of African BL. This contrasts to the absence of EBV in all, or almost all, of the non-African Burkitt's lymphoma-like tumors, even though the number of tested tumors in this group is small, and to the lack of EBV in all other types of lymphoma or leukemia. Immunological studies have revealed the presence of antibodies to different EBV-associated antigens in all African patients with Burkitt's lymphoma. However the antibodies are not specific for Burkitt's lymphoma but are found in most adults all over the world, although at lower levels. They cannot therefore serve diagnostic purposes, but they can give prognostic information and occasionally give clues to the mechanisms behind late tumor recurrences, and possibly guide so-called immunotherapy. Burkitt's lymphoma patients contrast to appropriate control groups where some of the persons are anti-EBV seronegative, and this, together with the presence of EBV in Burkitt's lymphoma biopsies and the absence of EBV in other lymphomas, even though the cell type involved may be infectable by EBV in vitro and the tumor may arise in an EBV-carrying person, favors an etiological role in EBV in Burkitt's lymphoma and speaks against the \"passenger\" hypothesis, according to which EBV is picked up by the Burkitt's lymphoma cell which happens to be particularly suitable for EBV persistence. To explain the geographical distribution, a cofactor, such as certain forms of malaria, has been implied.", "contents": "Burkitt's lymphoma - a human tumor model system for immunological studies. Burkitt's lymphoma occurs mainly in parts of tropical Africa and has attracted the attention of experimental workers due to its epidemiological and clinical features, which indicate a viral etiology and a host immune response to the tumor. As a result of virological studies, Epstein-Barr virus (EBV) DNA has been demonstrated in almost all tested biopsies of African BL. This contrasts to the absence of EBV in all, or almost all, of the non-African Burkitt's lymphoma-like tumors, even though the number of tested tumors in this group is small, and to the lack of EBV in all other types of lymphoma or leukemia. Immunological studies have revealed the presence of antibodies to different EBV-associated antigens in all African patients with Burkitt's lymphoma. However the antibodies are not specific for Burkitt's lymphoma but are found in most adults all over the world, although at lower levels. They cannot therefore serve diagnostic purposes, but they can give prognostic information and occasionally give clues to the mechanisms behind late tumor recurrences, and possibly guide so-called immunotherapy. Burkitt's lymphoma patients contrast to appropriate control groups where some of the persons are anti-EBV seronegative, and this, together with the presence of EBV in Burkitt's lymphoma biopsies and the absence of EBV in other lymphomas, even though the cell type involved may be infectable by EBV in vitro and the tumor may arise in an EBV-carrying person, favors an etiological role in EBV in Burkitt's lymphoma and speaks against the \"passenger\" hypothesis, according to which EBV is picked up by the Burkitt's lymphoma cell which happens to be particularly suitable for EBV persistence. To explain the geographical distribution, a cofactor, such as certain forms of malaria, has been implied."} {"id": "PMID:175836", "title": "Apoproteins of human serum high density lipoproteins. Isolation and characterization of the peptides of Sephadex fraction V from normal subjects and patients with abeta-lipoproteinemia.", "content": "1. Sephadex fraction V, obtained from human serum high density lipoprotein apoprotein (HDL apoprotein) of normal subjects and of patients with abetalipoproteinemia, was resolved by DEAE-cellulose ion exchange column chromatography into several fractions which were defined in terms of amino acid composition, NH2- and COOH-terminsls, sialic acid content, immunologic and electrophoretic properties, and in vitro activation of purified lipoprotein lipase from rat adipose tissue. 2. Fraction V of HDL apoprotein of both normal and abetalipoproteinemic subjects was found to contain polypeptides corresponding to apolipoproteins C-I, C-II, C-III-1, and C-III-2, which had been described previously in very low-density lipoproteins (VLDL). The content of apo C-III-1 in abetalipoproteinemia-HDL was very low, whereas the percentage, by weight, of apo C-I was about twice as high as that in the normal subjects studied. Furthermore, both normal and abetalipoproteinemia-HDL apoprotein contained a previously unreported peptide which had a molecular weight of about 7 000 and electrophoretic, chemical, and immunological properties distinct from those of the known C apolipoproteins. Of all of the peptides comprising fraction V, only apo C-II activated a purified preparation of rat adipose tissue lipoprotein lipase. This was the case for both normal and abetalipoproteinemic subjects.", "contents": "Apoproteins of human serum high density lipoproteins. Isolation and characterization of the peptides of Sephadex fraction V from normal subjects and patients with abeta-lipoproteinemia. 1. Sephadex fraction V, obtained from human serum high density lipoprotein apoprotein (HDL apoprotein) of normal subjects and of patients with abetalipoproteinemia, was resolved by DEAE-cellulose ion exchange column chromatography into several fractions which were defined in terms of amino acid composition, NH2- and COOH-terminsls, sialic acid content, immunologic and electrophoretic properties, and in vitro activation of purified lipoprotein lipase from rat adipose tissue. 2. Fraction V of HDL apoprotein of both normal and abetalipoproteinemic subjects was found to contain polypeptides corresponding to apolipoproteins C-I, C-II, C-III-1, and C-III-2, which had been described previously in very low-density lipoproteins (VLDL). The content of apo C-III-1 in abetalipoproteinemia-HDL was very low, whereas the percentage, by weight, of apo C-I was about twice as high as that in the normal subjects studied. Furthermore, both normal and abetalipoproteinemia-HDL apoprotein contained a previously unreported peptide which had a molecular weight of about 7 000 and electrophoretic, chemical, and immunological properties distinct from those of the known C apolipoproteins. Of all of the peptides comprising fraction V, only apo C-II activated a purified preparation of rat adipose tissue lipoprotein lipase. This was the case for both normal and abetalipoproteinemic subjects."} {"id": "PMID:175837", "title": "Isolation and characterization of the major apolipoprotein from chicken high density lipoproteins.", "content": "High density lipoproteins were isolated from plasma of white Leghorn hens by ultracentrifugal flotation between densities 1.063 and 1.210 g/ml. After delipidation, the lipid-free proteins were fractionated by chromatography on Sephadex G-150 in urea; one major apolipoprotein was isolated and characterized. From its chemical, physical and immunochemical properties, the major apoprotein from hen high-density lipoproteins has characteristics similar to the major apoprotein of human high density lipoproteins, apoA-I. Thus the hen protein has been designated hen apoA-I. Hen apoA-I has a molecular weight of approximately 28 000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Its calculated molecular weight from its 234 constituent amino acids is 26 674. Hen apoA-I differed from its human counterpart by containing isoleucine. Treatment of hen apoA-I with carboxypeptidase A yielded a COOH-terminal sequence of Leu-Val-Ala-Gln. Automatic Edman degradation of the apoprotein gave an NH2-terminal sequence of Asp-Glu-Pro-Gln-Pro-Glu-Leu. Hen apoA-I had a circular dichroic spectrum typical of alpha-helical structures; the calculated helicity was 90%. Goat antisera prepared to hen apoA-I formed precipitin lines of complete identity to the hen apoprotein but lines of only partial identity to human apoA-I. These studies show that the major apoprotein from hen and human high-density lipoproteins have similar properties to each other suggesting a common physiologic function.", "contents": "Isolation and characterization of the major apolipoprotein from chicken high density lipoproteins. High density lipoproteins were isolated from plasma of white Leghorn hens by ultracentrifugal flotation between densities 1.063 and 1.210 g/ml. After delipidation, the lipid-free proteins were fractionated by chromatography on Sephadex G-150 in urea; one major apolipoprotein was isolated and characterized. From its chemical, physical and immunochemical properties, the major apoprotein from hen high-density lipoproteins has characteristics similar to the major apoprotein of human high density lipoproteins, apoA-I. Thus the hen protein has been designated hen apoA-I. Hen apoA-I has a molecular weight of approximately 28 000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Its calculated molecular weight from its 234 constituent amino acids is 26 674. Hen apoA-I differed from its human counterpart by containing isoleucine. Treatment of hen apoA-I with carboxypeptidase A yielded a COOH-terminal sequence of Leu-Val-Ala-Gln. Automatic Edman degradation of the apoprotein gave an NH2-terminal sequence of Asp-Glu-Pro-Gln-Pro-Glu-Leu. Hen apoA-I had a circular dichroic spectrum typical of alpha-helical structures; the calculated helicity was 90%. Goat antisera prepared to hen apoA-I formed precipitin lines of complete identity to the hen apoprotein but lines of only partial identity to human apoA-I. These studies show that the major apoprotein from hen and human high-density lipoproteins have similar properties to each other suggesting a common physiologic function."} {"id": "PMID:175838", "title": "Rabbit alveolar macrophage collagenase: evidence of polymeric forms.", "content": "Collagenase harvested in vitro from rabbit alveolar macrophages eluted in gel chromatography corresponding to apparent molecular weights of 45 000, 85 000, and 165 000. Reversible changes from one molecular weight to another in low salt concentration and predominance of the 45 000 species in salt concentrations above 1.0 M (NaCl, KCl) suggest that the higher molecular weights represent polymeric forms of collagenase.", "contents": "Rabbit alveolar macrophage collagenase: evidence of polymeric forms. Collagenase harvested in vitro from rabbit alveolar macrophages eluted in gel chromatography corresponding to apparent molecular weights of 45 000, 85 000, and 165 000. Reversible changes from one molecular weight to another in low salt concentration and predominance of the 45 000 species in salt concentrations above 1.0 M (NaCl, KCl) suggest that the higher molecular weights represent polymeric forms of collagenase."} {"id": "PMID:175839", "title": "Change in ATP-pyrophosphohydrolase activity during spherule formation of Physarum polycephalum.", "content": "The activity of Ca2+-dependent ATP pyrophosphohydrolase was found to fluctuate during spherule formation of the acellular slime mold Physarum polycephalum under starving incubation. The enzyme activity increased up to 16-fold at the 3rd day of the starvation, then decreased drastically to less than its original level. Column chromatography of the enzyme preparation suggested that the increase in the activity was due to de novo synthesis of a new isozyme. Cycloheximide inhibited the synthesis. The two isozymes were different in their Ca2+ sensitivity, the new one being less sensitive.", "contents": "Change in ATP-pyrophosphohydrolase activity during spherule formation of Physarum polycephalum. The activity of Ca2+-dependent ATP pyrophosphohydrolase was found to fluctuate during spherule formation of the acellular slime mold Physarum polycephalum under starving incubation. The enzyme activity increased up to 16-fold at the 3rd day of the starvation, then decreased drastically to less than its original level. Column chromatography of the enzyme preparation suggested that the increase in the activity was due to de novo synthesis of a new isozyme. Cycloheximide inhibited the synthesis. The two isozymes were different in their Ca2+ sensitivity, the new one being less sensitive."} {"id": "PMID:175840", "title": "Effect of prostaglandin E on the adenyl cyclase-cyclic AMP system and gluconeogenesis in rat renal cortical slices.", "content": "Prostaglandin E was found to increase the formation of cyclic acdenosine 3',5'-monophosphate (cyclic AMP) by renal cortical slices. This increased release of cyclic AMP was not influenced by the absence of Ca2+ in the incubating media. The enhanced production of cyclic AMP was probably mediated by stimulation of membrane-bound adenylate cyclase activity. An increase in adenyl cyclase activity was observed with increasing concentrations of prostaglandin E. Furthermore, prostaglandin E augmented glucose production from alpha-ketoglutarate. This effect on gluconeogenesis was abolished by the removal of Ca2+ from the incubating medium. These effects are similar to those described for parathyroid hormone and suggest that the renal cortex is a prostaglandin-dependent system. Prostaglandin E decreased cyclic AMP production and glucose production (from alpha-ketoglutarate) in response to submaximal doses of parathyroid hormone, suggesting that prostaglandin may be important in modulating the intracelluar action of parathyroid hormone in the kidney cortex.", "contents": "Effect of prostaglandin E on the adenyl cyclase-cyclic AMP system and gluconeogenesis in rat renal cortical slices. Prostaglandin E was found to increase the formation of cyclic acdenosine 3',5'-monophosphate (cyclic AMP) by renal cortical slices. This increased release of cyclic AMP was not influenced by the absence of Ca2+ in the incubating media. The enhanced production of cyclic AMP was probably mediated by stimulation of membrane-bound adenylate cyclase activity. An increase in adenyl cyclase activity was observed with increasing concentrations of prostaglandin E. Furthermore, prostaglandin E augmented glucose production from alpha-ketoglutarate. This effect on gluconeogenesis was abolished by the removal of Ca2+ from the incubating medium. These effects are similar to those described for parathyroid hormone and suggest that the renal cortex is a prostaglandin-dependent system. Prostaglandin E decreased cyclic AMP production and glucose production (from alpha-ketoglutarate) in response to submaximal doses of parathyroid hormone, suggesting that prostaglandin may be important in modulating the intracelluar action of parathyroid hormone in the kidney cortex."} {"id": "PMID:175841", "title": "Localization of cell groups sensitive to parathyroid hormone and calcitonin in rat skeletal tissue.", "content": "The level of cyclic AMP in various fractions of rat skeletal tissue was measured after in vitro or in vivo administration of parathyroid hormone and calcitonin. Incubations of bone fractions prepared from young (5 weeks of age thyroparathyroidectomized rats revealed that both parathyroid hormone and calcitonin increased the cyclic AMP level in fractions of epiphysis, metaphysis and marrow cells. Cyclic AMP accumulation in incubated perisoteum and diaphysis were induced solely by parathyroid hormone. In in vivo experiments the cyclic AMP level in the tibia of the thyroparathyroidectomized rat was increased by infusion of either parathyroid hormone or calcitonin, and the simultaneous administration of each maximally effective dose of the two hormones exhibited an additive effect. Within 2 min, parathyroid hormone infusion caused an elevation of cyclic AMP content in periosteum and metaphysis. Rapid increase of cyclic AMP in the metaphysis was also induced by calcitonin, and the effect of the two hormones on cyclic AMP accumulation in this fraction was additive. Small but significant increase of cyclic AMP in the diaphysis was detected at 5 min after the administration of parathyroid hormone. Calcitonin infusion did not show any consistent effects on periosteum and diaphysis.", "contents": "Localization of cell groups sensitive to parathyroid hormone and calcitonin in rat skeletal tissue. The level of cyclic AMP in various fractions of rat skeletal tissue was measured after in vitro or in vivo administration of parathyroid hormone and calcitonin. Incubations of bone fractions prepared from young (5 weeks of age thyroparathyroidectomized rats revealed that both parathyroid hormone and calcitonin increased the cyclic AMP level in fractions of epiphysis, metaphysis and marrow cells. Cyclic AMP accumulation in incubated perisoteum and diaphysis were induced solely by parathyroid hormone. In in vivo experiments the cyclic AMP level in the tibia of the thyroparathyroidectomized rat was increased by infusion of either parathyroid hormone or calcitonin, and the simultaneous administration of each maximally effective dose of the two hormones exhibited an additive effect. Within 2 min, parathyroid hormone infusion caused an elevation of cyclic AMP content in periosteum and metaphysis. Rapid increase of cyclic AMP in the metaphysis was also induced by calcitonin, and the effect of the two hormones on cyclic AMP accumulation in this fraction was additive. Small but significant increase of cyclic AMP in the diaphysis was detected at 5 min after the administration of parathyroid hormone. Calcitonin infusion did not show any consistent effects on periosteum and diaphysis."} {"id": "PMID:175842", "title": "Dietary and hormonal regulation of some enzyme activities associated with gluconeogenesis in rabbit liver.", "content": "1. Starvation increases the activity of cytosolic P-enolpyruvate carboxkinase in rabbit liver some 4-5 fold but does not alter the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase or glucose-6-phosphatase.2. Alloxan-induced diabetes increases the activities of cytosolic P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase approx. 6-, 2- and 2-fold, respectively. Again the activity of mitochondrial P-enolpyruvate carboxykinase is not altered. 3. Administration of mannoheptulose rapidly increases blood glucose levels and also causes a significant increase in cytosolic P-enolpyruvate carboyxkinase activity within 4 h. The activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase are not affected. 4. Administration of hydrocortisone also increases blood glucose levels and the activities of cytosolic P-enolpyruvate carboxykinase and glucose-6-phosphatase are significantly increased within 12h. Again, mitochondrial P-enolpyruvate carboxykinase and fructose-1,6-diphosphatase activities remain unaffected. 5. The observations that (A) the activity of cytosolic P-enolpyruvate carboxykinase responds to more situations conducive to gluconeogenesis than do the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase, and (B) cytosolic P-enolpyruvate carboxykinase activity is rapidly adaptive under appropriate circumstances, suggests that this particular enzyme's activity plays an important role in the regulation of gluconeogenesis in rabbits.", "contents": "Dietary and hormonal regulation of some enzyme activities associated with gluconeogenesis in rabbit liver. 1. Starvation increases the activity of cytosolic P-enolpyruvate carboxkinase in rabbit liver some 4-5 fold but does not alter the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase or glucose-6-phosphatase.2. Alloxan-induced diabetes increases the activities of cytosolic P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase approx. 6-, 2- and 2-fold, respectively. Again the activity of mitochondrial P-enolpyruvate carboxykinase is not altered. 3. Administration of mannoheptulose rapidly increases blood glucose levels and also causes a significant increase in cytosolic P-enolpyruvate carboyxkinase activity within 4 h. The activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase are not affected. 4. Administration of hydrocortisone also increases blood glucose levels and the activities of cytosolic P-enolpyruvate carboxykinase and glucose-6-phosphatase are significantly increased within 12h. Again, mitochondrial P-enolpyruvate carboxykinase and fructose-1,6-diphosphatase activities remain unaffected. 5. The observations that (A) the activity of cytosolic P-enolpyruvate carboxykinase responds to more situations conducive to gluconeogenesis than do the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase, and (B) cytosolic P-enolpyruvate carboxykinase activity is rapidly adaptive under appropriate circumstances, suggests that this particular enzyme's activity plays an important role in the regulation of gluconeogenesis in rabbits."} {"id": "PMID:175843", "title": "Regulation by insulin of gluconeogenesis in isolated rat hepatocytes.", "content": "Insulin (10nM) completely suppressed the stimulation of gluconeogenesis from 2 mM lactate by low concentrations of glucagon (less than or equal to 0.1 nM) or cyclic AMP (less than or equal to 10 muM), but it had no effect on the basal rate of gluconeogenesis in hepatocyctes from fed rats. The effectiveness of insulin diminished as the concentration of these agonists increased, but insulin was able to suppress by 40% the stimulation by a maximally effective concentration of epinephrine (1 muM). The response to glucagon, epinephrine, or insulin was not dependent upon protein synthesis as cycloheximide did not alter their effects. Insulin also suppressed the stimulation by isoproterenol of cyclic GMP. These data are the first demonstration of insulin antagonism to the stimulation of gluconeogenesis by catecholamines. Insulin reduced cyclic AMP levels which had been elevated by low concentrations of glucagon or by 1 muM epinephrine. This supports the hypothesis that the action of insulin to inhibit gluconeogenesis is mediated by the lowering of cyclic AMP levels. However, evidence is presented which indicates that insulin is able to suppress the stimulation of gluconeogenesis by glucagon or epinephrine under conditions where either the agonists or insulin had no measurable effect on cyclic AMP levels. Insulin reduced the glucagon stimulation of gluconeogenesis whether or not extracellular Ca2+ were present, even though insulin only lowered cyclic AMP levels in their presence. Insulin also reduced the stimulation by epinephrine plus propranolol where no significant changes in cyclic AMP were observed without or with insulin. In addition, insulin suppressed gluconeogenesis in cells that had been preincubated with epinephrine for 20 min, even though the cyclic AMP levels had returned to near basal values and were unaffected by insulin. Thus insulin may not need to lower cyclic AMP levels in order to suppress gluconeogenesis.", "contents": "Regulation by insulin of gluconeogenesis in isolated rat hepatocytes. Insulin (10nM) completely suppressed the stimulation of gluconeogenesis from 2 mM lactate by low concentrations of glucagon (less than or equal to 0.1 nM) or cyclic AMP (less than or equal to 10 muM), but it had no effect on the basal rate of gluconeogenesis in hepatocyctes from fed rats. The effectiveness of insulin diminished as the concentration of these agonists increased, but insulin was able to suppress by 40% the stimulation by a maximally effective concentration of epinephrine (1 muM). The response to glucagon, epinephrine, or insulin was not dependent upon protein synthesis as cycloheximide did not alter their effects. Insulin also suppressed the stimulation by isoproterenol of cyclic GMP. These data are the first demonstration of insulin antagonism to the stimulation of gluconeogenesis by catecholamines. Insulin reduced cyclic AMP levels which had been elevated by low concentrations of glucagon or by 1 muM epinephrine. This supports the hypothesis that the action of insulin to inhibit gluconeogenesis is mediated by the lowering of cyclic AMP levels. However, evidence is presented which indicates that insulin is able to suppress the stimulation of gluconeogenesis by glucagon or epinephrine under conditions where either the agonists or insulin had no measurable effect on cyclic AMP levels. Insulin reduced the glucagon stimulation of gluconeogenesis whether or not extracellular Ca2+ were present, even though insulin only lowered cyclic AMP levels in their presence. Insulin also reduced the stimulation by epinephrine plus propranolol where no significant changes in cyclic AMP were observed without or with insulin. In addition, insulin suppressed gluconeogenesis in cells that had been preincubated with epinephrine for 20 min, even though the cyclic AMP levels had returned to near basal values and were unaffected by insulin. Thus insulin may not need to lower cyclic AMP levels in order to suppress gluconeogenesis."} {"id": "PMID:175844", "title": "Effect of adenosine 3',5'-cyclic monophosphate derivatives on alpha-amylase release, protein kinase and cyclic nucleotide phosphodiesterase activity from rat parotid tissue.", "content": "Several 8-substituted derivatives of cyclic AMP were tested for their effects on alpha-amylase release. None of the 8-substituted compounds were more active than N6,O2-dibutyryl- or N6-monobutyryl adenosine 3',5'-monophosphate in causing alpha-amylase release. The rat parotid was found to contain a high (105 muM) and a low (1.15 muM) Km cyclic AMP phosphodiesterase activity. All of the 8-substituted cyclic AMP compounds inhibited the hydrolysis of 1 muM cyclic AMP. However, there was only a partial correlation between the ability to cause alpha-amylase release and inhibit cyclic AMP hydrolysis. Extracts of parotid tissue contained a cyclic AMP-dependent protein kinase activity. None of the compounds were as effective as cyclic AMP in activating the protein kinase. As in the case of inhibition of cyclic AMP hydrolysis, the ability of the 8-substituted cyclic AMP compounds to increase protein kinase activity did not correlate with their effects on alpha-amylase release. It is concluded that factors in addition to the in vitro inhibition of cyclic AMP hydrolysis and activation of protein kinase are important in determining the net result of the 8-substituted cyclic AMP compounds on parotid gland function. These additional factors might include differences in the rate of uptake and differences in rats of conversion to compounds with modified activity.", "contents": "Effect of adenosine 3',5'-cyclic monophosphate derivatives on alpha-amylase release, protein kinase and cyclic nucleotide phosphodiesterase activity from rat parotid tissue. Several 8-substituted derivatives of cyclic AMP were tested for their effects on alpha-amylase release. None of the 8-substituted compounds were more active than N6,O2-dibutyryl- or N6-monobutyryl adenosine 3',5'-monophosphate in causing alpha-amylase release. The rat parotid was found to contain a high (105 muM) and a low (1.15 muM) Km cyclic AMP phosphodiesterase activity. All of the 8-substituted cyclic AMP compounds inhibited the hydrolysis of 1 muM cyclic AMP. However, there was only a partial correlation between the ability to cause alpha-amylase release and inhibit cyclic AMP hydrolysis. Extracts of parotid tissue contained a cyclic AMP-dependent protein kinase activity. None of the compounds were as effective as cyclic AMP in activating the protein kinase. As in the case of inhibition of cyclic AMP hydrolysis, the ability of the 8-substituted cyclic AMP compounds to increase protein kinase activity did not correlate with their effects on alpha-amylase release. It is concluded that factors in addition to the in vitro inhibition of cyclic AMP hydrolysis and activation of protein kinase are important in determining the net result of the 8-substituted cyclic AMP compounds on parotid gland function. These additional factors might include differences in the rate of uptake and differences in rats of conversion to compounds with modified activity."} {"id": "PMID:175846", "title": "An EPR study of myeloperoxidase in human granulocytes.", "content": "1. EPR spectra of human granulocytes (4 - 10(8) cells per ml) show an intense high-spin ferric heme signal with rhombic symmetry (gx = 6.90 and gy = 5.07) for the heme group. These g-values are identical to those of partially purified myeloperoxidase and thus the signal is derived from ferric myeloperoxidase. In chicken granulocytes, which contain little or no myeloperoxidase, only an axial type of heme iron signal, weak in intensity, can be detected at g = 6.0. 2. Upon phagocytosis of latex particles by human granulocytes the high-spin heme signal with rhombic symmetry is slowly converted into a signal with axial symmetry (gx = gy = 6.0), showing that the EPR signals of myeloperoxidase in the intact cell can be used to study the involvement of the enzyme in metabolic changes during phagocytosis.", "contents": "An EPR study of myeloperoxidase in human granulocytes. 1. EPR spectra of human granulocytes (4 - 10(8) cells per ml) show an intense high-spin ferric heme signal with rhombic symmetry (gx = 6.90 and gy = 5.07) for the heme group. These g-values are identical to those of partially purified myeloperoxidase and thus the signal is derived from ferric myeloperoxidase. In chicken granulocytes, which contain little or no myeloperoxidase, only an axial type of heme iron signal, weak in intensity, can be detected at g = 6.0. 2. Upon phagocytosis of latex particles by human granulocytes the high-spin heme signal with rhombic symmetry is slowly converted into a signal with axial symmetry (gx = gy = 6.0), showing that the EPR signals of myeloperoxidase in the intact cell can be used to study the involvement of the enzyme in metabolic changes during phagocytosis."} {"id": "PMID:175847", "title": "Cyclic AMP formation and morphology of myocardial cells isolated from adult heart: effect of Ca2+ and Mg2+.", "content": "Adult rat heart cells were isolated by perfusion with a calcium-free phosphate buffer containing collagenase. Optimal conditions gave a high proportion of elongated cells. Isoprenaline increased cydic AMP content linearly, with ED50 (dose effective in 50% of the population) about 10(-7) M. Ca2+ made the cells spherical, and it nearly abolished cyclic AMP response as did lack of Mg2+.", "contents": "Cyclic AMP formation and morphology of myocardial cells isolated from adult heart: effect of Ca2+ and Mg2+. Adult rat heart cells were isolated by perfusion with a calcium-free phosphate buffer containing collagenase. Optimal conditions gave a high proportion of elongated cells. Isoprenaline increased cydic AMP content linearly, with ED50 (dose effective in 50% of the population) about 10(-7) M. Ca2+ made the cells spherical, and it nearly abolished cyclic AMP response as did lack of Mg2+."} {"id": "PMID:175848", "title": "Nervonic acid biosynthesis by erucyl-CoA elongation in normal and quaking mouse brain microsomes. Elongation of other unsaturated fatty acyl-CoAs (mono and poly-unsaturated).", "content": "Biosynthesis of nervonic acid by enzymatic elongation of erucyl-CoA has been studied in mouse brain microsomes. The substrate and cofactor requirements have been measured. Malonyl-CoA and reduced nicotine-adenine-dinucleotide phosphate are required, but not FMN, FAD or NADH. The effect of protein concentration, incubation time, ATP and CoA has been determined; the reaction products were checked by gas-liquid chromatography with automatic counting of the eluate. Very little activity was found in hydroxylated fatty acids. In the presence of phosphotransacetylase (which impedes the de novo microsomal system), the main reaction product was nervonic acid. It is concluded that nervonic acid is biosynthesised by elongation using a two-carbon unit from malonyl-CoA. The same enzyme biosynthesises saturated and mono-unsaturated very long chain fatty acids. The elongation capacity of \"quaking\" microsomes is reduced to 30% of the normal value with both erucyl-CoA and behenyl-CoA. Elongation of trans isomer (brassidyl-CoA) and poly-unsaturated homologue (clupanodonyl-CoA) was compared to elongation of erucyl-CoA in both normal and mutant mice. Both unsaturated acyl-CoAs are elongated under the same conditions as erucyl-CoA in brain: the poly-unsaturated acyl-CoA is elongated more actively than the mono-unsaturated acyl-CoA in the mutant.", "contents": "Nervonic acid biosynthesis by erucyl-CoA elongation in normal and quaking mouse brain microsomes. Elongation of other unsaturated fatty acyl-CoAs (mono and poly-unsaturated). Biosynthesis of nervonic acid by enzymatic elongation of erucyl-CoA has been studied in mouse brain microsomes. The substrate and cofactor requirements have been measured. Malonyl-CoA and reduced nicotine-adenine-dinucleotide phosphate are required, but not FMN, FAD or NADH. The effect of protein concentration, incubation time, ATP and CoA has been determined; the reaction products were checked by gas-liquid chromatography with automatic counting of the eluate. Very little activity was found in hydroxylated fatty acids. In the presence of phosphotransacetylase (which impedes the de novo microsomal system), the main reaction product was nervonic acid. It is concluded that nervonic acid is biosynthesised by elongation using a two-carbon unit from malonyl-CoA. The same enzyme biosynthesises saturated and mono-unsaturated very long chain fatty acids. The elongation capacity of \"quaking\" microsomes is reduced to 30% of the normal value with both erucyl-CoA and behenyl-CoA. Elongation of trans isomer (brassidyl-CoA) and poly-unsaturated homologue (clupanodonyl-CoA) was compared to elongation of erucyl-CoA in both normal and mutant mice. Both unsaturated acyl-CoAs are elongated under the same conditions as erucyl-CoA in brain: the poly-unsaturated acyl-CoA is elongated more actively than the mono-unsaturated acyl-CoA in the mutant."} {"id": "PMID:175849", "title": "Characterization of the Ehrlich ascites tumor plasma lipoproteins.", "content": "1. The lipoproteins of the Ehrlich ascites tumor plasma were separated into 3 distinct fractions, very low density, low density and high density lipoproteins by preparative ultracentrifugation combined with agarose column chromatography. 2. High density lipoproteins contained 74% of the total protein in the lipoproteins. By contrast, most of the lipids were present in the very low density lipoprotein fraction. 3. The fatty acid compositions of the cholesteryl esters were appreciably different in the very low, low and high density lipoproteins, whereas phospholipid and triacylglycerol fatty acid compositions were quite similar in the 3 lipoprotein fractions. 4. Very low and high density apoprotein electrophoretic patterns on sodium dodecyl sulfate-acrylamide gels were similar to those observed in the corresponding lipoprotein fractions obtained from other mammalian species. The low density fraction, however, contained 7 apoprotein bands, and 32% of the low density apoprotein was soluble in tetramethyl urea. 5. The average molecular weights as determined by analytical ultracentrifugation were 2-10(7) (very low density), 6-10(6) (low density) and 4.4-10(5) (high density).", "contents": "Characterization of the Ehrlich ascites tumor plasma lipoproteins. 1. The lipoproteins of the Ehrlich ascites tumor plasma were separated into 3 distinct fractions, very low density, low density and high density lipoproteins by preparative ultracentrifugation combined with agarose column chromatography. 2. High density lipoproteins contained 74% of the total protein in the lipoproteins. By contrast, most of the lipids were present in the very low density lipoprotein fraction. 3. The fatty acid compositions of the cholesteryl esters were appreciably different in the very low, low and high density lipoproteins, whereas phospholipid and triacylglycerol fatty acid compositions were quite similar in the 3 lipoprotein fractions. 4. Very low and high density apoprotein electrophoretic patterns on sodium dodecyl sulfate-acrylamide gels were similar to those observed in the corresponding lipoprotein fractions obtained from other mammalian species. The low density fraction, however, contained 7 apoprotein bands, and 32% of the low density apoprotein was soluble in tetramethyl urea. 5. The average molecular weights as determined by analytical ultracentrifugation were 2-10(7) (very low density), 6-10(6) (low density) and 4.4-10(5) (high density)."} {"id": "PMID:175850", "title": "High performance preparative column chromatography of lipids using a new porous silica, Iatrobeads. I. Separation of molecular species of sphingoglycolipids.", "content": "Good preparative separation of neutral glycolipids of human erythrocytes was achieved by column chromatography using the totally porous silica spheres, Iatrobeads. The solvent flow through the Iatrobeads column was rapid under atmospheric pressure, and so elution bands migrated with minimal diffusion in the column. Ceramide dihexoside and ceramide trihexoside were both separated into two fractions of different molecular species on the Iatrobeads column. Two ceramide tetrasaccharides, globoside I and paragloboside, were also clearly separated on the Iatrobeads column. Chemical analysis showed that separation of these molecular species was due to differences in their fatty acid and long chain base compositions. Sphingadienine and phytosphingosine were found as minor components of long chain bases in human erythrocyte glycolipids.", "contents": "High performance preparative column chromatography of lipids using a new porous silica, Iatrobeads. I. Separation of molecular species of sphingoglycolipids. Good preparative separation of neutral glycolipids of human erythrocytes was achieved by column chromatography using the totally porous silica spheres, Iatrobeads. The solvent flow through the Iatrobeads column was rapid under atmospheric pressure, and so elution bands migrated with minimal diffusion in the column. Ceramide dihexoside and ceramide trihexoside were both separated into two fractions of different molecular species on the Iatrobeads column. Two ceramide tetrasaccharides, globoside I and paragloboside, were also clearly separated on the Iatrobeads column. Chemical analysis showed that separation of these molecular species was due to differences in their fatty acid and long chain base compositions. Sphingadienine and phytosphingosine were found as minor components of long chain bases in human erythrocyte glycolipids."} {"id": "PMID:175851", "title": "Characterisation of the small molecular weight apolipoproteins from pig plasma very low density lipoprotein.", "content": "The small molecular weight apolipoproteins of pig very low density lipoprotein were investigated following their separation by gel filtration and ion exchange chromatography. Gel filtration through Sephadex G-200 in 6 M urea, produced essentially the same elution profile to that obtained after filtration of human very low density apolipoprotein. However, separation of the pig Sephadex fraction corresponding to human C proteins on DEAE-cellulose columns revealed the presence of only one major peptide and minor quantities of several others. Some properties of three apparent homogeneous fractions and one heterogeneous DEAE fraction were investigated. Unlike human apoprotein CII apoprotein, none of the pig peptides studied activated cow's milk lipase and sialic acid was not detected in any of the three purified C peptides of pig VLDL. The amino acid compositions of the pig peptides were different to those reported for human C apoproteins. The carboxy terminal residue of the major pig C peptide was shown to be serine. The differences so far revealed between pig and human C peptides need further investigation especially since this animal is regarded as a suitable model for investigating human lipoprotein metabolism and the development of atherosclerosis.", "contents": "Characterisation of the small molecular weight apolipoproteins from pig plasma very low density lipoprotein. The small molecular weight apolipoproteins of pig very low density lipoprotein were investigated following their separation by gel filtration and ion exchange chromatography. Gel filtration through Sephadex G-200 in 6 M urea, produced essentially the same elution profile to that obtained after filtration of human very low density apolipoprotein. However, separation of the pig Sephadex fraction corresponding to human C proteins on DEAE-cellulose columns revealed the presence of only one major peptide and minor quantities of several others. Some properties of three apparent homogeneous fractions and one heterogeneous DEAE fraction were investigated. Unlike human apoprotein CII apoprotein, none of the pig peptides studied activated cow's milk lipase and sialic acid was not detected in any of the three purified C peptides of pig VLDL. The amino acid compositions of the pig peptides were different to those reported for human C apoproteins. The carboxy terminal residue of the major pig C peptide was shown to be serine. The differences so far revealed between pig and human C peptides need further investigation especially since this animal is regarded as a suitable model for investigating human lipoprotein metabolism and the development of atherosclerosis."} {"id": "PMID:175852", "title": "Random cleavage of superhelical SV 40 DNA S1 nuclease.", "content": "SV40 DNA FO I is randomly cleaved by S1 nuclease both at moderate (50 mM) and higher salt concentrations (250 mM NaC1). Full length linear S1 cleavage products of SV40 DNA when digested with various restriction endonucleases revealed fragments that were electrophoretically indistinguishable from the products found after digestion of superhelical SV40 DNA FO I with the corresponding enzyme. Concordingly, when the linear S1 generated duplexes were melted and renatured, circular duplexes were formed in addition to complex larger structures. This indicated that cleavage must have occurred at different sites. The double-strand-cleaving activity present in S1 nuclease preparations requires circular DNA as a substrate, as linear SV40 DNA is not cleaved. With regard to these properties S1 nuclease resembles some of the complex type I restriction nucleases from Escherichia coli which also cleave SV40 DNA only once, and, completely at random.", "contents": "Random cleavage of superhelical SV 40 DNA S1 nuclease. SV40 DNA FO I is randomly cleaved by S1 nuclease both at moderate (50 mM) and higher salt concentrations (250 mM NaC1). Full length linear S1 cleavage products of SV40 DNA when digested with various restriction endonucleases revealed fragments that were electrophoretically indistinguishable from the products found after digestion of superhelical SV40 DNA FO I with the corresponding enzyme. Concordingly, when the linear S1 generated duplexes were melted and renatured, circular duplexes were formed in addition to complex larger structures. This indicated that cleavage must have occurred at different sites. The double-strand-cleaving activity present in S1 nuclease preparations requires circular DNA as a substrate, as linear SV40 DNA is not cleaved. With regard to these properties S1 nuclease resembles some of the complex type I restriction nucleases from Escherichia coli which also cleave SV40 DNA only once, and, completely at random."} {"id": "PMID:175853", "title": "The fragments from the 28 S ribosomal RNA of Galleria mellonella with unesterified uridine at the 3'-termini.", "content": "The three 3'-ends of the 28 S galleria RNA are all unesterified uridines. The two 18-S products due to the primary nick of the 28 S RNA have a similar 3'-terminal dinucleotide: G-Uoh. All of the seven species of secondary products from the Galleria 28 S RNA were suggested to have unesterified uridines, in common, at the 3'-ends. These results raise the possibility that the enzyme concerned in generating the primary and secondary nicks is a uracil-specific and 5'-phosphate-forming phosphodiesterase. The esterase, in association with the higher structure of the rRNA molecule in the larger subunit of the ribosome, probably determines the sites for these nicks in the 28 S rRNA. It is proposed also that the same enzyme can be responsible for cleaving the 28-S and 5.8-S rRNAs from their immediate precursor molecules.", "contents": "The fragments from the 28 S ribosomal RNA of Galleria mellonella with unesterified uridine at the 3'-termini. The three 3'-ends of the 28 S galleria RNA are all unesterified uridines. The two 18-S products due to the primary nick of the 28 S RNA have a similar 3'-terminal dinucleotide: G-Uoh. All of the seven species of secondary products from the Galleria 28 S RNA were suggested to have unesterified uridines, in common, at the 3'-ends. These results raise the possibility that the enzyme concerned in generating the primary and secondary nicks is a uracil-specific and 5'-phosphate-forming phosphodiesterase. The esterase, in association with the higher structure of the rRNA molecule in the larger subunit of the ribosome, probably determines the sites for these nicks in the 28 S rRNA. It is proposed also that the same enzyme can be responsible for cleaving the 28-S and 5.8-S rRNAs from their immediate precursor molecules."} {"id": "PMID:175854", "title": "G1 specific increases in cyclic AMP levels and protein kinase activity in Chinese hamster ovary cells.", "content": "Chinese hamster ovary cells were synchronized by selective detachment of cells in mitosis. The adenosine 3':5'-cyclic monophosphate (cyclic AMP) intracellular concentrations and cyclic AMP-dependent protein kinase activities were measured as these cells traversed G1 phase and entered S phase. Protein kinase activity, assayed in the presence or absence of saturating exogenous cyclic AMP in the reaction mixture, was lowest in early G1 phase (2 h after mitosis), increased 2-fold (plus exogenous cyclic AMP in reaction mixture) or 3.5-fold (minus cyclic AMP in reaction mixture) to maximum values in mid to late G1 phase (4-5 h after mitosis), and then decreased as cells entered S phase. Intracellular cyclic AMP concentrations were minimal 1 h after mitosis, increased 5-fold to maximum levels at 4-6 after mitosis, and decreased as cells entered S phase. Similar to the fluctuations in intracellular cyclic AMP, the cyclic AMP-dependent protein kinase activity ratio increased more than 40% in late G1 or early S phase. Puromycin (either 10 mug/ml or 50 mug/ml) administered 1 h after mitosis inhibited cyclic AMP-dependent protein kinase activity up to 50% by 5 h after mitosis, while similar treatment (10 mug/ml) had no effect on the increase in cyclic AMP formation. These data demonstrate that: (1) total protein kinase activity changed during G1 phase and this increase was dependent on new protein synthesis; (2) the increased intracellular concentrations of cyclic AMP were not dependent on new protein synthesis; and (3) the activation of cyclic AMP-dependent protein kinase was temporally coordinated with increased intracellular concentration of cycli AMP as Chinese hamster ovary cells traversed G1 phase and entered S phase. These results suggest that cyclic AMP acts during G1 phase to regulate the activation of cyclic AMP-dependent protein kinase.", "contents": "G1 specific increases in cyclic AMP levels and protein kinase activity in Chinese hamster ovary cells. Chinese hamster ovary cells were synchronized by selective detachment of cells in mitosis. The adenosine 3':5'-cyclic monophosphate (cyclic AMP) intracellular concentrations and cyclic AMP-dependent protein kinase activities were measured as these cells traversed G1 phase and entered S phase. Protein kinase activity, assayed in the presence or absence of saturating exogenous cyclic AMP in the reaction mixture, was lowest in early G1 phase (2 h after mitosis), increased 2-fold (plus exogenous cyclic AMP in reaction mixture) or 3.5-fold (minus cyclic AMP in reaction mixture) to maximum values in mid to late G1 phase (4-5 h after mitosis), and then decreased as cells entered S phase. Intracellular cyclic AMP concentrations were minimal 1 h after mitosis, increased 5-fold to maximum levels at 4-6 after mitosis, and decreased as cells entered S phase. Similar to the fluctuations in intracellular cyclic AMP, the cyclic AMP-dependent protein kinase activity ratio increased more than 40% in late G1 or early S phase. Puromycin (either 10 mug/ml or 50 mug/ml) administered 1 h after mitosis inhibited cyclic AMP-dependent protein kinase activity up to 50% by 5 h after mitosis, while similar treatment (10 mug/ml) had no effect on the increase in cyclic AMP formation. These data demonstrate that: (1) total protein kinase activity changed during G1 phase and this increase was dependent on new protein synthesis; (2) the increased intracellular concentrations of cyclic AMP were not dependent on new protein synthesis; and (3) the activation of cyclic AMP-dependent protein kinase was temporally coordinated with increased intracellular concentration of cycli AMP as Chinese hamster ovary cells traversed G1 phase and entered S phase. These results suggest that cyclic AMP acts during G1 phase to regulate the activation of cyclic AMP-dependent protein kinase."} {"id": "PMID:175855", "title": "Membrane studies of Streptococcus pyogenes and its L-form growing in hypertonic and physiologically isotonic media. An electron spin resonance spectroscopy approach.", "content": "Electron spin resonance spectroscopy (ESR) was used to compare the lipid organization, thermal stability and the physical state of the membrane of a human pathogen, Streptococcus pyogenes and its osmotically fragile L-form with this same L-form now adapted to grow under physiologically isotonic conditions (physiological L-form). Comparison of the hyperfine splittings of a derivative of 5-ketostearic acid spin label, I(12, 3), after incorporation into the membrane, revealed that the lipid chain rigidity of these membranes is in the order physiological L-form greater than osmotically fragile L-form greater than streptococcus. The signal intensity (of the center magnetic field line) versus temperature analysis showed two transitions for these membranes. The first with melting points of 45, 26 and 36 degrees C and second transition at 70, 63 and 60 degrees C for the physiological L-form, osmotically fragile L-form and streptococcal membranes, respectively. This same order of membrane lipid chain rigidity was seen from the cooperativities obtained for each of these systems from analysis based on the expression for an n-order reaction. The I(12, 3) and other probes with the paramagnetic group close to the methyl end of the molecule suggested that this difference in lipid chain rigidity between these organisms resides in the environment closer to the lipid head group region rather than in the hydrophobic lipid core. Another major finding was the binding of I(12, 3) at two or more different sites in each of the membranes examined. This change in lipid chain rigidity now provides an explanation to account for the survival of a previously osmotically fragile L-form in physiologically isotonic media by focusing on changes in the physical nature of its membrane. In so doing, it adds to and reinforces the speculation of the potential survival in vivo and involvement in pathogenesis of osmotically fragile aberrant forms of bacteria.", "contents": "Membrane studies of Streptococcus pyogenes and its L-form growing in hypertonic and physiologically isotonic media. An electron spin resonance spectroscopy approach. Electron spin resonance spectroscopy (ESR) was used to compare the lipid organization, thermal stability and the physical state of the membrane of a human pathogen, Streptococcus pyogenes and its osmotically fragile L-form with this same L-form now adapted to grow under physiologically isotonic conditions (physiological L-form). Comparison of the hyperfine splittings of a derivative of 5-ketostearic acid spin label, I(12, 3), after incorporation into the membrane, revealed that the lipid chain rigidity of these membranes is in the order physiological L-form greater than osmotically fragile L-form greater than streptococcus. The signal intensity (of the center magnetic field line) versus temperature analysis showed two transitions for these membranes. The first with melting points of 45, 26 and 36 degrees C and second transition at 70, 63 and 60 degrees C for the physiological L-form, osmotically fragile L-form and streptococcal membranes, respectively. This same order of membrane lipid chain rigidity was seen from the cooperativities obtained for each of these systems from analysis based on the expression for an n-order reaction. The I(12, 3) and other probes with the paramagnetic group close to the methyl end of the molecule suggested that this difference in lipid chain rigidity between these organisms resides in the environment closer to the lipid head group region rather than in the hydrophobic lipid core. Another major finding was the binding of I(12, 3) at two or more different sites in each of the membranes examined. This change in lipid chain rigidity now provides an explanation to account for the survival of a previously osmotically fragile L-form in physiologically isotonic media by focusing on changes in the physical nature of its membrane. In so doing, it adds to and reinforces the speculation of the potential survival in vivo and involvement in pathogenesis of osmotically fragile aberrant forms of bacteria."} {"id": "PMID:175856", "title": "[EPR spectra of silkworm eggs].", "content": "ESR spectra of the native grain of the silkworm have been studied in the course of embryo formation, during a diapause, and during embryo development after the diapause. It is shown that the nature of ESR spectra of the grain is not determined by the metabolic processes, but by the presence of pigments in it and other stationary biological structures having developed pi-systems and unpaired electrones. The latter are mainly found in the envelope and may give the ESR spectra, with various g-factors. A dependence of the ESR spectra integral intensity of the grain on the denotype is discovered.", "contents": "[EPR spectra of silkworm eggs]. ESR spectra of the native grain of the silkworm have been studied in the course of embryo formation, during a diapause, and during embryo development after the diapause. It is shown that the nature of ESR spectra of the grain is not determined by the metabolic processes, but by the presence of pigments in it and other stationary biological structures having developed pi-systems and unpaired electrones. The latter are mainly found in the envelope and may give the ESR spectra, with various g-factors. A dependence of the ESR spectra integral intensity of the grain on the denotype is discovered."} {"id": "PMID:175863", "title": "Parameters in the construction of an immobilized dual enzyme catalyst.", "content": "The glucose oxidase and catalase activities immobilized to the gamma-aminopropyltriethoxysilane derivative of nickel-impregnated silica alumina was controlled by several factors. The most important of these was enzyme concentration. In constructing the dual immobilized enzyme catalyst, competition between the two enzymes for available binding sites was observed. The order of addition of the various reactants during immobilization was also important. Higher glucose oxidase activities were immobilized when glutaraldehyde was added concurrently with enzyme, while maximal coupling of catalase occurred if glutaraldehyde was first added to react with the amino derivative of the silica alumina support, excess reagent washed away, and then the catalase added. Bovine serum albumin, which aids in the crosslinking of glucose oxidase, hindered the coupling of the enzyme to the support particles.", "contents": "Parameters in the construction of an immobilized dual enzyme catalyst. The glucose oxidase and catalase activities immobilized to the gamma-aminopropyltriethoxysilane derivative of nickel-impregnated silica alumina was controlled by several factors. The most important of these was enzyme concentration. In constructing the dual immobilized enzyme catalyst, competition between the two enzymes for available binding sites was observed. The order of addition of the various reactants during immobilization was also important. Higher glucose oxidase activities were immobilized when glutaraldehyde was added concurrently with enzyme, while maximal coupling of catalase occurred if glutaraldehyde was first added to react with the amino derivative of the silica alumina support, excess reagent washed away, and then the catalase added. Bovine serum albumin, which aids in the crosslinking of glucose oxidase, hindered the coupling of the enzyme to the support particles."} {"id": "PMID:175857", "title": "[Effect of lyophilization on the free-radical state of animal cells].", "content": "The process of lyophylisation carried out very carefully under strictly defined conditions does not in inself bring about the changes in the parameters of the ESR signal with g approximately equal to 2.00 observed in animal cells. The free radicals responsible for the ESR signal observed under usual experimental conditions, result from a contact of the lyophylised specimen with moisture at an optimum water content of about 10%.", "contents": "[Effect of lyophilization on the free-radical state of animal cells]. The process of lyophylisation carried out very carefully under strictly defined conditions does not in inself bring about the changes in the parameters of the ESR signal with g approximately equal to 2.00 observed in animal cells. The free radicals responsible for the ESR signal observed under usual experimental conditions, result from a contact of the lyophylised specimen with moisture at an optimum water content of about 10%."} {"id": "PMID:175864", "title": "Electrolytic regeneration of the reduced from the oxidized form of immobilized NAD.", "content": "A covalently bound adduct of nicotinamide adenine dinucleotide (NAD) with alginic acid has been found to be enzymatically active and to undergo electrochemical oxidation or reduction without significant loss of its enzymatic activity. The preparation of the adduct itself (from NAD+, alginic acid, and 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide metho-p-toluenesulfonate) is also accomplished with substantially complete retention of enzymatic activity. This adduct has been converted from the oxidized to the reduced form by controlled potential electrolysis using mercury and stainless-steel electrodes. This electrolytically produced NADH complex could be oxidized again to the enzymatically active NAD+ complex by enzymatic reaction with the proton acceptor, 2,6-dichlorophenol indophenol, as catalyzed by diaphorase. Using this electrolytic method with immobilized NAD, it is now possible to carry out redox reactions in which NADH is enzymatically oxidized to NAD+, with the simultaneous electrolytic regeneration of the reduced form, NADH, from the oxidized form, NAD+, produced in the enzymatic reaction.", "contents": "Electrolytic regeneration of the reduced from the oxidized form of immobilized NAD. A covalently bound adduct of nicotinamide adenine dinucleotide (NAD) with alginic acid has been found to be enzymatically active and to undergo electrochemical oxidation or reduction without significant loss of its enzymatic activity. The preparation of the adduct itself (from NAD+, alginic acid, and 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide metho-p-toluenesulfonate) is also accomplished with substantially complete retention of enzymatic activity. This adduct has been converted from the oxidized to the reduced form by controlled potential electrolysis using mercury and stainless-steel electrodes. This electrolytically produced NADH complex could be oxidized again to the enzymatically active NAD+ complex by enzymatic reaction with the proton acceptor, 2,6-dichlorophenol indophenol, as catalyzed by diaphorase. Using this electrolytic method with immobilized NAD, it is now possible to carry out redox reactions in which NADH is enzymatically oxidized to NAD+, with the simultaneous electrolytic regeneration of the reduced form, NADH, from the oxidized form, NAD+, produced in the enzymatic reaction."} {"id": "PMID:175865", "title": "Pilot plant production of glucose with glucoamylase immobilized to porous silica.", "content": "Glucoamylase was immobilized to porous silica and its kinetics and stability were observed with acid- and alpha-amylase-hydrolyzed dextrin as feed. The enzyme was found to be extremely stable in both laboratory and pilot plant operations. When the feed had been previously only lightly hydrolyzed, pore diffusion limitation caused appreciable decreases in glucose production rate. The severity of starch hydrolysis to dextrin markedly affected ultimate glucose yields. The diffusional gradients present in the carrier pores caused the immobilized enzyme to yield lower glucose concentrations than the free enzyme at similar feed conditions.", "contents": "Pilot plant production of glucose with glucoamylase immobilized to porous silica. Glucoamylase was immobilized to porous silica and its kinetics and stability were observed with acid- and alpha-amylase-hydrolyzed dextrin as feed. The enzyme was found to be extremely stable in both laboratory and pilot plant operations. When the feed had been previously only lightly hydrolyzed, pore diffusion limitation caused appreciable decreases in glucose production rate. The severity of starch hydrolysis to dextrin markedly affected ultimate glucose yields. The diffusional gradients present in the carrier pores caused the immobilized enzyme to yield lower glucose concentrations than the free enzyme at similar feed conditions."} {"id": "PMID:175866", "title": "[The effect of extracardiac nerves on the intensity of glycogen metabolism in cardiac muscle].", "content": "The left vagus was cut in rats on the neck; this was followed by a reduction of the glycogen content in the myocardium and by an increase in the intensity of its metabolism (by the glucose-I-C14 incorporation). Sympathetic denervation of the heart led to the increase in the glycogen level and a fall of the intensity of its metabolism in the cardiac muscle.", "contents": "[The effect of extracardiac nerves on the intensity of glycogen metabolism in cardiac muscle]. The left vagus was cut in rats on the neck; this was followed by a reduction of the glycogen content in the myocardium and by an increase in the intensity of its metabolism (by the glucose-I-C14 incorporation). Sympathetic denervation of the heart led to the increase in the glycogen level and a fall of the intensity of its metabolism in the cardiac muscle."} {"id": "PMID:175867", "title": "[Changes in the sensitivity of developing sea urchin embryos to prostaglandin F2alpha and cyclic 3',5'-adenosine monophosphate].", "content": "It was shown that at various stages of the first mitotic cycles the developing ova of Strongylocentrotus intermedius displayed a different sensitivity to toxic concentrations of prostaglandin F2alpha and to cyclic 3',5'-adenosinmonophosphate (cAMP). The differences in the sensitivity to each of these substances were regular and similar in character and depended on the time lapse after the completion of division next in turn. There were revealed two periods of increased sensitivity of the ova--the first one--during the 20th minute after the completion of each division--to both substances, and the second one--during the 40th minute--to cAMP, and during the 50th minute--to prostaglandin F2alpha.", "contents": "[Changes in the sensitivity of developing sea urchin embryos to prostaglandin F2alpha and cyclic 3',5'-adenosine monophosphate]. It was shown that at various stages of the first mitotic cycles the developing ova of Strongylocentrotus intermedius displayed a different sensitivity to toxic concentrations of prostaglandin F2alpha and to cyclic 3',5'-adenosinmonophosphate (cAMP). The differences in the sensitivity to each of these substances were regular and similar in character and depended on the time lapse after the completion of division next in turn. There were revealed two periods of increased sensitivity of the ova--the first one--during the 20th minute after the completion of each division--to both substances, and the second one--during the 40th minute--to cAMP, and during the 50th minute--to prostaglandin F2alpha."} {"id": "PMID:175868", "title": "[Ultrastructural study of a Masson's \"humid meningioma\"].", "content": "The authors report the ultrastructural analysis of a Masson's humic meningioma. The tumor presents at the electronic microscopic examination every sign of secretive hyperactivity and does not show any degenerative characteristics. The existence of an important extracellular material rich in pre-collagenic fibres accounts for lacunar texture of this neoplasia at optic microscopic investigation; the role played by tumoral cells in the elaboration of the material is taken into account and seems to corroborate histogenic ecto-mesenchymatous theory of arachnoidal cells.", "contents": "[Ultrastructural study of a Masson's \"humid meningioma\"]. The authors report the ultrastructural analysis of a Masson's humic meningioma. The tumor presents at the electronic microscopic examination every sign of secretive hyperactivity and does not show any degenerative characteristics. The existence of an important extracellular material rich in pre-collagenic fibres accounts for lacunar texture of this neoplasia at optic microscopic investigation; the role played by tumoral cells in the elaboration of the material is taken into account and seems to corroborate histogenic ecto-mesenchymatous theory of arachnoidal cells."} {"id": "PMID:175872", "title": "Prosthetic restoration in congenital lower limb deficiency. A case study.", "content": "We presented a synopsis of a young girl with congenitally deficient limb who underwent seven corrective surgical procedures and fabrication of a specially designed and constructed prosthesis. The surgical procedures are detailed as in the total rehabilitation approach. We have provided plastic laminated orthoses and prostheses to many patients with congenitally deficient upper and lower limbs. An additional paper will detail our experience with a series of plastic laminated orthoses and prostheses in patients with congentally deficient upper and lower extremities.", "contents": "Prosthetic restoration in congenital lower limb deficiency. A case study. We presented a synopsis of a young girl with congenitally deficient limb who underwent seven corrective surgical procedures and fabrication of a specially designed and constructed prosthesis. The surgical procedures are detailed as in the total rehabilitation approach. We have provided plastic laminated orthoses and prostheses to many patients with congenitally deficient upper and lower limbs. An additional paper will detail our experience with a series of plastic laminated orthoses and prostheses in patients with congentally deficient upper and lower extremities."} {"id": "PMID:175869", "title": "[Epidemiology in the study of the role of viruses in human cancers].", "content": "An epidemiological approach is very useful in the study of the role of viruses in the development of human tumors, if properly integrated with the experimental approach and laboratory studies. Certain epidemiological characteristics of human tumours favour a viral etiology, e.g. space and time clustering, vertical and horizontal transmission of a tumour risk, succession in space or in time of viral induced benign lesions and of malignant tumours. In the framework of the association between the EB herpesvirus and both Burkitt's lymphoma and nasopharyngeal carcinoma, we conducted an epidemiological survey of the EBV infection in populations at different risk for EBV associated diseases. This survey showed that, in Uganda, the EBV infection was much earlier and heavier than in Hong Kong or Singapore. A hypothesis that early infection is related to BL risk is discussed as well as the value of epidemiology in both prospective studies and in prevention of virally induced tumours. The IARC prospective sero-epidemiological study on Burkitt's lymphoma and EBV in Uganda is given as an exemplar.", "contents": "[Epidemiology in the study of the role of viruses in human cancers]. An epidemiological approach is very useful in the study of the role of viruses in the development of human tumors, if properly integrated with the experimental approach and laboratory studies. Certain epidemiological characteristics of human tumours favour a viral etiology, e.g. space and time clustering, vertical and horizontal transmission of a tumour risk, succession in space or in time of viral induced benign lesions and of malignant tumours. In the framework of the association between the EB herpesvirus and both Burkitt's lymphoma and nasopharyngeal carcinoma, we conducted an epidemiological survey of the EBV infection in populations at different risk for EBV associated diseases. This survey showed that, in Uganda, the EBV infection was much earlier and heavier than in Hong Kong or Singapore. A hypothesis that early infection is related to BL risk is discussed as well as the value of epidemiology in both prospective studies and in prevention of virally induced tumours. The IARC prospective sero-epidemiological study on Burkitt's lymphoma and EBV in Uganda is given as an exemplar."} {"id": "PMID:175873", "title": "The influence of motor nerve tetanization on the effect of organophosphorus cholinesterase inhibitors on neuromuscular transmission.", "content": "1. The changes in the activity of synaptic cholinesterases (ChE) of the ant. tibial muscle in the anaesthetized cat were detected by recording the changes of the blocking activity of acetylcholine (ACh) and comparing them with the blocking activity of carbaminoylcholine (carbachol) injected intra-arterially or intravenously. After the administration of organophosphorus inhibitors (OPI) of ChE the ACh blocking dose diminished 500 to 2000-fold but the carbachol blocking dose did not change. In 4-6 h after the injection of OPI the ACh blocking dose increased again 8 to 15-fold, but the dose of carbachol still remained unchanged. The transmission of high frequency impulses improved after OPI in parallel with the decrease of the ACh blocking activity. Thus the synaptic ChE is partly restored in a few hours after its irreversible inhibition with OPI. 2. Tetanization of the motor nerve (50-60 Hz, 10 min), started simultaneously with the intravenous injection of OPI (armine Gd-42), diminished the impairment of neuromuscular transmission. On the side of tetanization the ACh blocking action was less pronounced and the transmission of high frequency impulses better than on the control side. Thus the tetanization produced some protection of synaptic ChE against inhibition by OPI. The protective effect of tetanization was absent when the tetanization was performed before the injection of OPI or was started 10-20 min after the injection of OPI. 3. The protective effect of tetanization was also observed on the isolated phrenic nerve diaphragm preparation of the rat. 4. The possible mechanisms of the protective effect of tetanization are discussed.", "contents": "The influence of motor nerve tetanization on the effect of organophosphorus cholinesterase inhibitors on neuromuscular transmission. 1. The changes in the activity of synaptic cholinesterases (ChE) of the ant. tibial muscle in the anaesthetized cat were detected by recording the changes of the blocking activity of acetylcholine (ACh) and comparing them with the blocking activity of carbaminoylcholine (carbachol) injected intra-arterially or intravenously. After the administration of organophosphorus inhibitors (OPI) of ChE the ACh blocking dose diminished 500 to 2000-fold but the carbachol blocking dose did not change. In 4-6 h after the injection of OPI the ACh blocking dose increased again 8 to 15-fold, but the dose of carbachol still remained unchanged. The transmission of high frequency impulses improved after OPI in parallel with the decrease of the ACh blocking activity. Thus the synaptic ChE is partly restored in a few hours after its irreversible inhibition with OPI. 2. Tetanization of the motor nerve (50-60 Hz, 10 min), started simultaneously with the intravenous injection of OPI (armine Gd-42), diminished the impairment of neuromuscular transmission. On the side of tetanization the ACh blocking action was less pronounced and the transmission of high frequency impulses better than on the control side. Thus the tetanization produced some protection of synaptic ChE against inhibition by OPI. The protective effect of tetanization was absent when the tetanization was performed before the injection of OPI or was started 10-20 min after the injection of OPI. 3. The protective effect of tetanization was also observed on the isolated phrenic nerve diaphragm preparation of the rat. 4. The possible mechanisms of the protective effect of tetanization are discussed."} {"id": "PMID:175870", "title": "[DNA form of the genome of oncornaviruses].", "content": "The oncornaviruses share several biological, biochemical, and structural properties that distinguish them from other RNA viruses. Rous sarcoma virus, a representative of avian oncornaviruses, manifests two major functions: cell transformation and virus replication. Both functions are independent, and are expressed separately in defective viruses. The virus has a 60-70S RNA, composed of 35 S subunits. It appears that each subunit of viral RNA carries the same genetic information and, furthermore, that 10% of this information is coding for cell transformation. Without this 10% the virus can still replicate. The RNA genome is expressed when the virus penetrates a sensitive cell, provided the virus carries an active reverse transcriptase. Virus-transformed cells possess a DNA form of the viral genome. The viral DNA is infectious, and can lead, upon transfection of permissive cells, to the production of a new viral progeny. We have established that the minimum molecular weight of the viral DNA is 6 X 10(6) daltons, and that this DNA is covalently bound to the chromosomal DNA. Also by examining the frequency of transfection events in the DNA-treated cells we suggest that transfection is a single-hit phenomenon. It follows that viral DNA of 6 X 10(6) daltons carries all the genetic information to code for the virus production. It seems likely that the transfection mechanism giving rise to transforming viruses is different from that producing nontransforming segments. In general terms, the experimental data indicate that certain RNAs and DNAs could accomplish malignant transformation if they are able to penetrate into the cell and give rise to the DNA forms which could be integrated into the cellular genome.", "contents": "[DNA form of the genome of oncornaviruses]. The oncornaviruses share several biological, biochemical, and structural properties that distinguish them from other RNA viruses. Rous sarcoma virus, a representative of avian oncornaviruses, manifests two major functions: cell transformation and virus replication. Both functions are independent, and are expressed separately in defective viruses. The virus has a 60-70S RNA, composed of 35 S subunits. It appears that each subunit of viral RNA carries the same genetic information and, furthermore, that 10% of this information is coding for cell transformation. Without this 10% the virus can still replicate. The RNA genome is expressed when the virus penetrates a sensitive cell, provided the virus carries an active reverse transcriptase. Virus-transformed cells possess a DNA form of the viral genome. The viral DNA is infectious, and can lead, upon transfection of permissive cells, to the production of a new viral progeny. We have established that the minimum molecular weight of the viral DNA is 6 X 10(6) daltons, and that this DNA is covalently bound to the chromosomal DNA. Also by examining the frequency of transfection events in the DNA-treated cells we suggest that transfection is a single-hit phenomenon. It follows that viral DNA of 6 X 10(6) daltons carries all the genetic information to code for the virus production. It seems likely that the transfection mechanism giving rise to transforming viruses is different from that producing nontransforming segments. In general terms, the experimental data indicate that certain RNAs and DNAs could accomplish malignant transformation if they are able to penetrate into the cell and give rise to the DNA forms which could be integrated into the cellular genome."} {"id": "PMID:175874", "title": "The effect of edrophonium on erythrocyte acetylcholinesterase and neuromuscular function in the rat.", "content": "1. The relation between the concentration of edrophonium in plasma, inhibition of red cell acetylcholinesterase, and neuromuscular transmission was studied in the rat. 2. In both in vivo and in vitro conditions, red cell acetylcholinesterase activity was predictably related to the concentration of the quaternary amine. 3. After low doses of edrophonium (1.0 mumol/kg) there was a significant correlation between the monophasic potentiation of twitch tension and the plasma concentration of the drug. In contrast, with higher doses of edrophonium (4.0 or 10.0 mumol/kg) a biphasic potentiation of twitch tension was observed; this was only correlated with the plasma concentration of the drug during the secondary decline in neuromuscular facilitation. Subsequent recovery of normal neuromuscular transmission invariably occurred at a constant plasma concentration of edrophonium.", "contents": "The effect of edrophonium on erythrocyte acetylcholinesterase and neuromuscular function in the rat. 1. The relation between the concentration of edrophonium in plasma, inhibition of red cell acetylcholinesterase, and neuromuscular transmission was studied in the rat. 2. In both in vivo and in vitro conditions, red cell acetylcholinesterase activity was predictably related to the concentration of the quaternary amine. 3. After low doses of edrophonium (1.0 mumol/kg) there was a significant correlation between the monophasic potentiation of twitch tension and the plasma concentration of the drug. In contrast, with higher doses of edrophonium (4.0 or 10.0 mumol/kg) a biphasic potentiation of twitch tension was observed; this was only correlated with the plasma concentration of the drug during the secondary decline in neuromuscular facilitation. Subsequent recovery of normal neuromuscular transmission invariably occurred at a constant plasma concentration of edrophonium."} {"id": "PMID:175871", "title": "[Host-leukemogenic virus relation: genetic control of the appearance of leukemia].", "content": "A complex genetic system controls the susceptibility to virus induced leukemia. A good example is provided by AKR mice in which several genes acting in association are involved. The control is demonstrable at several levels: a) virus expression, b) virus replication, c) antitumor immune response. In addition one or two other genes could be involved. The \"Leukemia-permissive\" genotype would be probably rarely present and the AKR provides the model of a mice in which all genetic locus bear the permissive alleles.", "contents": "[Host-leukemogenic virus relation: genetic control of the appearance of leukemia]. A complex genetic system controls the susceptibility to virus induced leukemia. A good example is provided by AKR mice in which several genes acting in association are involved. The control is demonstrable at several levels: a) virus expression, b) virus replication, c) antitumor immune response. In addition one or two other genes could be involved. The \"Leukemia-permissive\" genotype would be probably rarely present and the AKR provides the model of a mice in which all genetic locus bear the permissive alleles."} {"id": "PMID:175875", "title": "Hypothalamo-pituitary adrenocortical function in the rat after treatment with betamethasone.", "content": "1 Hypothalamo-pituitary-adrenocortical (HPA) activity was suppressed in rats treated with betamethasone. 2 Recovery of normal HPA function occurred after corticosteroid withdrawl. 3 Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached 'supra-normal' levels. 4 The physiological significance and possible clinical relevance of the results are discussed.", "contents": "Hypothalamo-pituitary adrenocortical function in the rat after treatment with betamethasone. 1 Hypothalamo-pituitary-adrenocortical (HPA) activity was suppressed in rats treated with betamethasone. 2 Recovery of normal HPA function occurred after corticosteroid withdrawl. 3 Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached 'supra-normal' levels. 4 The physiological significance and possible clinical relevance of the results are discussed."} {"id": "PMID:175876", "title": "A genetic model of narcolepsy.", "content": "An analysis of recently published family history data on rapid eye movement (REM) narcolepsy was undertaken to determine the goodness-of-fit of a multifactorial (MF) model of inheritance. The analysis revealed that a two-threshold MF model can successfully account for the prevalence of REM narcolepsy and other disorders of excessive sleep (DES) observed in the first-degree relatives of the REM narcoleptic probands studied.", "contents": "A genetic model of narcolepsy. An analysis of recently published family history data on rapid eye movement (REM) narcolepsy was undertaken to determine the goodness-of-fit of a multifactorial (MF) model of inheritance. The analysis revealed that a two-threshold MF model can successfully account for the prevalence of REM narcolepsy and other disorders of excessive sleep (DES) observed in the first-degree relatives of the REM narcoleptic probands studied."} {"id": "PMID:175877", "title": "Oculodento-digital dysplasia: a rare syndrome.", "content": "A rare syndrome that can be diagnosed radiographically has been reviewed. A characteristic physiognomy, variable ophthalmologic anomalies and relatively specific dental and digital defects provide the diagnostic features. No hereditary component was identified and the chromosomal pattern was normal. The history, appearance and characteristic radiographic changes may, as in this case, allow the radiologist to provide a diagnosis not previously appreciated.", "contents": "Oculodento-digital dysplasia: a rare syndrome. A rare syndrome that can be diagnosed radiographically has been reviewed. A characteristic physiognomy, variable ophthalmologic anomalies and relatively specific dental and digital defects provide the diagnostic features. No hereditary component was identified and the chromosomal pattern was normal. The history, appearance and characteristic radiographic changes may, as in this case, allow the radiologist to provide a diagnosis not previously appreciated."} {"id": "PMID:175882", "title": "Sterol synthesis by myelinating cultures of mouse spinal cord.", "content": "We studied the control of sterol synthesis during myelination of central nervous system in culture. Explants of fetal mouse spinal cord were cultured for 3-30 days in vitro (DIV). Myelination was visible by electron micriscopy at 3 DIV, and by bright-field light microscopy beginning at 6 DIV. All explants were heavily myelinated by 15 DIV. Specific activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) increased rapidly until 15 DIV. The rate of incorporation of [1-14C]acetate into sterol was greatest at 12 DIV, more than double that at 4 and 22 DIV. Specific activity of the mevalonate synthesizing enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) was greatest at 11 DIV, threefold greater than at 6 and 30 DIV. Previous studies in fibroblasts and other non-neural tissues had shown that deprivation of exogenous lipid caused a rapid increase in HMG CoA reductase activity. In contrast, when the spinal cord explants were incubated for 24 h in a lipid-deficient medium, there was either a marked decrease in specific activity of HMG CoA reductase (at 6, 15 and 30 DIV), or no change in enzyme activity (at 11 DIV).", "contents": "Sterol synthesis by myelinating cultures of mouse spinal cord. We studied the control of sterol synthesis during myelination of central nervous system in culture. Explants of fetal mouse spinal cord were cultured for 3-30 days in vitro (DIV). Myelination was visible by electron micriscopy at 3 DIV, and by bright-field light microscopy beginning at 6 DIV. All explants were heavily myelinated by 15 DIV. Specific activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) increased rapidly until 15 DIV. The rate of incorporation of [1-14C]acetate into sterol was greatest at 12 DIV, more than double that at 4 and 22 DIV. Specific activity of the mevalonate synthesizing enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) was greatest at 11 DIV, threefold greater than at 6 and 30 DIV. Previous studies in fibroblasts and other non-neural tissues had shown that deprivation of exogenous lipid caused a rapid increase in HMG CoA reductase activity. In contrast, when the spinal cord explants were incubated for 24 h in a lipid-deficient medium, there was either a marked decrease in specific activity of HMG CoA reductase (at 6, 15 and 30 DIV), or no change in enzyme activity (at 11 DIV)."} {"id": "PMID:175884", "title": "Hippocampal theta rhythm. II. Depth profiles in the freely moving rabbit.", "content": "Depth profiles of hippocampal theta rhythm were investigated in the freely moving rabbit during three behavioral conditions: REM sleep, voluntary movement, and during sensory stimulation applied to the motionless animal. Profiles were found to be the same in all three conditions. Dorsoventral microelectrode penetration of the dorsal hippocampus revealed an approximately uniform amplitude of theta rhythm in strata oriens and pyramidal of CA1. Further microelectrode advancement revealed a sharp reversal of phase and a coincident null in amplitude in the proximal stratum radiatum. There was also a peak of theta rhythm amplitude which occurred in the molecular layer of the dorsal blade of the dentate gyrus. These data imply that in the rabbit, as in the freely moving rat, there are two generators of theta rhythm in the dorsal hippocampus, one in the dentate gyrus and the other in the overlying CA1 layer. The data also indicate the existence of a species difference in generating systems between the rabbit and the rat.", "contents": "Hippocampal theta rhythm. II. Depth profiles in the freely moving rabbit. Depth profiles of hippocampal theta rhythm were investigated in the freely moving rabbit during three behavioral conditions: REM sleep, voluntary movement, and during sensory stimulation applied to the motionless animal. Profiles were found to be the same in all three conditions. Dorsoventral microelectrode penetration of the dorsal hippocampus revealed an approximately uniform amplitude of theta rhythm in strata oriens and pyramidal of CA1. Further microelectrode advancement revealed a sharp reversal of phase and a coincident null in amplitude in the proximal stratum radiatum. There was also a peak of theta rhythm amplitude which occurred in the molecular layer of the dorsal blade of the dentate gyrus. These data imply that in the rabbit, as in the freely moving rat, there are two generators of theta rhythm in the dorsal hippocampus, one in the dentate gyrus and the other in the overlying CA1 layer. The data also indicate the existence of a species difference in generating systems between the rabbit and the rat."} {"id": "PMID:175887", "title": "Glucocorticoid binding to receptor-like proteins in rat brain and pituitary: ontogenetic and experimentally induced changes.", "content": "Cytosol binding of [3H]corticosterone and [3H]dexamethasone was measured in various brain areas and the pituitary of perfused rats 12 h and 72 h, respectively, after adrenalectomy (ADX). A considerable regional heterogeneity was found 12 h post ADX representing differences of the normal cytosol binding capacities between various areas. When the second phase of the adrenalectomy-induced increase in binding capacity was allowed to develop (72 h post ADX), the cytosol binding of all regions increased to various extents. The highest percentage increases were found in those areas with the highest glucocorticoid binding capacity, namely the hippocampus and the septum. The ontogeny of the cytosol glucocorticoid binding macromolecules was investigated in the hippocampus, hypothalamus and pituitary using [3H]corticosterone and [3H]dexamethasone. The concentration of corticosterone binding sites is lowest in all three areas around day one and then increases by a factor of 2-3 reaching adult levels around day 32. For [3H]dexamethasone a similar pattern was observed in the hippocampus and hypothalamus. In the pituitary, however, the concentration of binding sites was slightly higher at day 1 than at any later developmental stage. Interruption of the fimbria in 3-day-old rats did not affect the development of the binding sites in the hippocampus. In an attempt to interfere with the normal glucocorticoid binding of the hippocampus as well as with the postadrenalectomy increase of the cytosol binding sites, bilateral transection of the fimbria was performed either 3 days or 80 days before ADX. In neither case did fimbria transection prevent the increase of the binding sites. The intrinsic (12 h post ADX) cytosol binding capacity of the hippocampus was also not affected by this lesion.", "contents": "Glucocorticoid binding to receptor-like proteins in rat brain and pituitary: ontogenetic and experimentally induced changes. Cytosol binding of [3H]corticosterone and [3H]dexamethasone was measured in various brain areas and the pituitary of perfused rats 12 h and 72 h, respectively, after adrenalectomy (ADX). A considerable regional heterogeneity was found 12 h post ADX representing differences of the normal cytosol binding capacities between various areas. When the second phase of the adrenalectomy-induced increase in binding capacity was allowed to develop (72 h post ADX), the cytosol binding of all regions increased to various extents. The highest percentage increases were found in those areas with the highest glucocorticoid binding capacity, namely the hippocampus and the septum. The ontogeny of the cytosol glucocorticoid binding macromolecules was investigated in the hippocampus, hypothalamus and pituitary using [3H]corticosterone and [3H]dexamethasone. The concentration of corticosterone binding sites is lowest in all three areas around day one and then increases by a factor of 2-3 reaching adult levels around day 32. For [3H]dexamethasone a similar pattern was observed in the hippocampus and hypothalamus. In the pituitary, however, the concentration of binding sites was slightly higher at day 1 than at any later developmental stage. Interruption of the fimbria in 3-day-old rats did not affect the development of the binding sites in the hippocampus. In an attempt to interfere with the normal glucocorticoid binding of the hippocampus as well as with the postadrenalectomy increase of the cytosol binding sites, bilateral transection of the fimbria was performed either 3 days or 80 days before ADX. In neither case did fimbria transection prevent the increase of the binding sites. The intrinsic (12 h post ADX) cytosol binding capacity of the hippocampus was also not affected by this lesion."} {"id": "PMID:175888", "title": "Interactions in vivo and in vitro of corticoids and progesterone with cell nuclei and soluble macromolecules from rat brain regions and pituitary.", "content": "Adrenalectomized-ovariectomized (ADX-OVX) rats were given tail vein infusions of [3H]corticosterone, dexamethasone, cortisol, deoxycorticosterone or progesterone in doses around 10 nmoles/kg body weight. After a 30-60 min uptake period, cell nuclei were isolated from 9 brain regions and pituitary. Patterns of cell nuclear retention of [3H]corticosterone and [3H]dexamethasone differed: the former steroid was highest in hippocampus and septum and low in pituitary; the latter steroid was highest in pituitary and more uniformly distributed in the brain. The other 3H steroids showed very little cell nuclear labeling in vivo. In contrast, in vitro cytosol binding in hippocampus for [3H]progesterone, cortisol, deoxycorticosterone, and dexamethasone was 40-60% of that observed for [3H]corticosterone. The specificity of cell nuclear binding in slices of hippocampus in vitro was similar to that observed for cytosol binding. Reasons for the selectivity of in vivo cell nuclear labeling remain to be discovered but the selectivity does not appear to be an intrinsic feature of the receptors themselves. The pattern of in vivo labeling by [3H]corticosterone and [3H]dexamethasone differs from the in vivo distribution of [3H]estradiol in ADX-OVX rats using the same dissection procedure and this demonstrates the regional differentiation within brain of steroid hormone uptake and 'receptor' processes.", "contents": "Interactions in vivo and in vitro of corticoids and progesterone with cell nuclei and soluble macromolecules from rat brain regions and pituitary. Adrenalectomized-ovariectomized (ADX-OVX) rats were given tail vein infusions of [3H]corticosterone, dexamethasone, cortisol, deoxycorticosterone or progesterone in doses around 10 nmoles/kg body weight. After a 30-60 min uptake period, cell nuclei were isolated from 9 brain regions and pituitary. Patterns of cell nuclear retention of [3H]corticosterone and [3H]dexamethasone differed: the former steroid was highest in hippocampus and septum and low in pituitary; the latter steroid was highest in pituitary and more uniformly distributed in the brain. The other 3H steroids showed very little cell nuclear labeling in vivo. In contrast, in vitro cytosol binding in hippocampus for [3H]progesterone, cortisol, deoxycorticosterone, and dexamethasone was 40-60% of that observed for [3H]corticosterone. The specificity of cell nuclear binding in slices of hippocampus in vitro was similar to that observed for cytosol binding. Reasons for the selectivity of in vivo cell nuclear labeling remain to be discovered but the selectivity does not appear to be an intrinsic feature of the receptors themselves. The pattern of in vivo labeling by [3H]corticosterone and [3H]dexamethasone differs from the in vivo distribution of [3H]estradiol in ADX-OVX rats using the same dissection procedure and this demonstrates the regional differentiation within brain of steroid hormone uptake and 'receptor' processes."} {"id": "PMID:175893", "title": "[Feline leukemogenic and sarcomatogenic viruses].", "content": "Feline Leukemia and sarcoma viruses (FeLV, FeSV) are RNA viruses, belonging to the Oncornavirus group. They possess common morphological, biochemical and immunological properties, with viruses of leukemia and sarcoma already known in others mammalian and avian species. FeLV is widely present in feline population and its transmission is by horizontal way. FeLV and FeSV are oncogenic for others species, i.e., dog and some non-human primates but as far as we know, the human receptivity is not established. A correlation between humoral antibody directed against membran new-antigens and regression of tumors induced by FeSV, led to actual investigations on vaccination.", "contents": "[Feline leukemogenic and sarcomatogenic viruses]. Feline Leukemia and sarcoma viruses (FeLV, FeSV) are RNA viruses, belonging to the Oncornavirus group. They possess common morphological, biochemical and immunological properties, with viruses of leukemia and sarcoma already known in others mammalian and avian species. FeLV is widely present in feline population and its transmission is by horizontal way. FeLV and FeSV are oncogenic for others species, i.e., dog and some non-human primates but as far as we know, the human receptivity is not established. A correlation between humoral antibody directed against membran new-antigens and regression of tumors induced by FeSV, led to actual investigations on vaccination."} {"id": "PMID:175894", "title": "Mode of C-type virus production by bone cells of C3H/Fg mice.", "content": "Electron microscopy of bone from the distal ends of femurs of six 3-month-old male C3H/Fg mice revealed varying modes and quantities of C-type virus production by cells in the preosteoblast to osteocyte developmental gradient. Production occurred by budding from the cell surface, either from very short pedicles or from longer microvillous-like processes. Although apparently absent in preosteoblasts, limited numbers of budding viruses (90-110 nM) were seen in 6 of 53 osteoblasts examined. Examination of 200 osteocytes revealed evidence of virus production in all but eight. In these cells, budding occurred from the cell body and its processes with release of viruses into the pericellular lacunar space. Budding from the longer microvillous-like processes sometimes resulted in binding together of viruses in bead-like fashion by thin strands of limiting membrane. In a few cases budding was also seen on the cell processes within the canaliculi. The quantities of viruses present within the lacunae usually increased with increasing age of the osteocytes, indicating continual virus production. Most of the viruses observed, however, were pre C-types along with lesser numbers of mature C particles. Thus, factors contributing to the production of mature C particles may be diminished in osteocytes of mice at this age.", "contents": "Mode of C-type virus production by bone cells of C3H/Fg mice. Electron microscopy of bone from the distal ends of femurs of six 3-month-old male C3H/Fg mice revealed varying modes and quantities of C-type virus production by cells in the preosteoblast to osteocyte developmental gradient. Production occurred by budding from the cell surface, either from very short pedicles or from longer microvillous-like processes. Although apparently absent in preosteoblasts, limited numbers of budding viruses (90-110 nM) were seen in 6 of 53 osteoblasts examined. Examination of 200 osteocytes revealed evidence of virus production in all but eight. In these cells, budding occurred from the cell body and its processes with release of viruses into the pericellular lacunar space. Budding from the longer microvillous-like processes sometimes resulted in binding together of viruses in bead-like fashion by thin strands of limiting membrane. In a few cases budding was also seen on the cell processes within the canaliculi. The quantities of viruses present within the lacunae usually increased with increasing age of the osteocytes, indicating continual virus production. Most of the viruses observed, however, were pre C-types along with lesser numbers of mature C particles. Thus, factors contributing to the production of mature C particles may be diminished in osteocytes of mice at this age."} {"id": "PMID:175895", "title": "Demonstration of cyclic AMP in bone cells by immuno-histochemical methods.", "content": "By utilizing immunohistochemical procedures it was possible to locate bone cells that contained adenosine 3'5'-monophosphate (cyclic AMP) in frozen, undecalcified cat jaw sections. An immunoglobulin-enzyme bridge method was found to be superior to other techniques, including immunofluorescence. Differences in staining pattern were found between bone cells of kittens and young adult cats, indicating different metabolic levels related to cellular maturity, and different intracellular compartmentalization of cyclic AMP in the two age groups.", "contents": "Demonstration of cyclic AMP in bone cells by immuno-histochemical methods. By utilizing immunohistochemical procedures it was possible to locate bone cells that contained adenosine 3'5'-monophosphate (cyclic AMP) in frozen, undecalcified cat jaw sections. An immunoglobulin-enzyme bridge method was found to be superior to other techniques, including immunofluorescence. Differences in staining pattern were found between bone cells of kittens and young adult cats, indicating different metabolic levels related to cellular maturity, and different intracellular compartmentalization of cyclic AMP in the two age groups."} {"id": "PMID:175896", "title": "Cellular localization of cyclic AMP in periodontal tissues during experimental tooth movement in cats.", "content": "Using an immune-histochemical method, cyclic AMP was localized in cells of periodontal tissues in orthodontically-treated cats. Sixteen cats were treated for periods ranging from 1 hour to 4 weeks. Fresh, frozen, undecalcified 6 mu sections of the tissues were incubated with rabbit anti-cyclic AMP antibodies, followed by sequential incubations with sheep anti-rabbit IgG, rabbit anti-peroxidase IgG and horseradish peroxidase. In the final step, the peroxidase was demonstrated by the diaminobenzidine (DAB) method. It was found that the number of intensely stained cells increased within a short time in areas in which bone resorption or apposition occurred later. However, differences in the pattern of cellular activation were found to exist between areas of compression and tension. The alveolar osteocytes appeared to be affected to only a slight degree by the applications of mechanical forces. These results indicate: (a) that our immune-histochemical method was useful in following the cellular distribution of cyclic AMP during bone remodeling; and (b) that mechanical forces may affect only a small part of the bone cell population and therefore cannot be regarded as an efficient means to bring about extensive bone remodeling.", "contents": "Cellular localization of cyclic AMP in periodontal tissues during experimental tooth movement in cats. Using an immune-histochemical method, cyclic AMP was localized in cells of periodontal tissues in orthodontically-treated cats. Sixteen cats were treated for periods ranging from 1 hour to 4 weeks. Fresh, frozen, undecalcified 6 mu sections of the tissues were incubated with rabbit anti-cyclic AMP antibodies, followed by sequential incubations with sheep anti-rabbit IgG, rabbit anti-peroxidase IgG and horseradish peroxidase. In the final step, the peroxidase was demonstrated by the diaminobenzidine (DAB) method. It was found that the number of intensely stained cells increased within a short time in areas in which bone resorption or apposition occurred later. However, differences in the pattern of cellular activation were found to exist between areas of compression and tension. The alveolar osteocytes appeared to be affected to only a slight degree by the applications of mechanical forces. These results indicate: (a) that our immune-histochemical method was useful in following the cellular distribution of cyclic AMP during bone remodeling; and (b) that mechanical forces may affect only a small part of the bone cell population and therefore cannot be regarded as an efficient means to bring about extensive bone remodeling."} {"id": "PMID:175897", "title": "Assembly of complex III into newly developing mitochondrial membranes.", "content": "Yeast cells grown anaerobically in 0.02% linoleic acid were transferred to air in the presence of 0.02% elaidic acid. At varying times Arrhenius plots were made of QH2-cytochrome c reductase activities in isolated mitochondria. A transition temperature of 8.2 degrees C at 0.5 h was characteristic of linoleate; at 3 h the transition temperature was increased to 24 degrees C characteristic of elaidate. At early times the enzyme was associated with anaerobic promitochondrial membranes; at later states the newly synthesized enzyme was associated with newly developed elaidate membranes.", "contents": "Assembly of complex III into newly developing mitochondrial membranes. Yeast cells grown anaerobically in 0.02% linoleic acid were transferred to air in the presence of 0.02% elaidic acid. At varying times Arrhenius plots were made of QH2-cytochrome c reductase activities in isolated mitochondria. A transition temperature of 8.2 degrees C at 0.5 h was characteristic of linoleate; at 3 h the transition temperature was increased to 24 degrees C characteristic of elaidate. At early times the enzyme was associated with anaerobic promitochondrial membranes; at later states the newly synthesized enzyme was associated with newly developed elaidate membranes."} {"id": "PMID:175898", "title": "3':5'-Cyclic-AMP phosphodiesterase activities in white and brown adipose tissues of cold-acclimated rats.", "content": "3':5'-Cyclic-AMP phosphodiesterase (PDE) (EC 3.1.4.17) activity was measured in interscapular brown adipose tissue (BAT) and in white epididymal adipose tissue of rats acclimated to constant or fluctuating cold. Experiments were carried out on isolated adipocytes or tissue homogenates. In brown or white adipose tissue or isolated adipocyte homogenates, two different apparent Km values were found according to the substrate (cAMP) concentration. The low Km was at about 10(-6) M and the high one at about 10(-4) M. The apparent V of the high Km enzyme was about 10-fold higher than the V of the low Km enzyme. Cold acclimation to constant or fluctuating cold did not modify appreciably the Km or V values. For low substrate concentrations (10(-6)-10(-8) M), the specific activity of PDE expressed per milligram of protein was decreased in BAT adipocytes of the two groups of cold-acclimated rats, compared to controls. Inversely, it was increased in total tissue homogenates. These variations were smaller in fluctuating cold than in constant cold-acclimate rats. They could, in part, induce the increases in lipolysis and in blood flow observed in the BAT of cold-acclimated rats.", "contents": "3':5'-Cyclic-AMP phosphodiesterase activities in white and brown adipose tissues of cold-acclimated rats. 3':5'-Cyclic-AMP phosphodiesterase (PDE) (EC 3.1.4.17) activity was measured in interscapular brown adipose tissue (BAT) and in white epididymal adipose tissue of rats acclimated to constant or fluctuating cold. Experiments were carried out on isolated adipocytes or tissue homogenates. In brown or white adipose tissue or isolated adipocyte homogenates, two different apparent Km values were found according to the substrate (cAMP) concentration. The low Km was at about 10(-6) M and the high one at about 10(-4) M. The apparent V of the high Km enzyme was about 10-fold higher than the V of the low Km enzyme. Cold acclimation to constant or fluctuating cold did not modify appreciably the Km or V values. For low substrate concentrations (10(-6)-10(-8) M), the specific activity of PDE expressed per milligram of protein was decreased in BAT adipocytes of the two groups of cold-acclimated rats, compared to controls. Inversely, it was increased in total tissue homogenates. These variations were smaller in fluctuating cold than in constant cold-acclimate rats. They could, in part, induce the increases in lipolysis and in blood flow observed in the BAT of cold-acclimated rats."} {"id": "PMID:175899", "title": "Inhibition of lymphocyte transformation: effect of soy bean trypsin inhibitor and synthetic anti-proteases.", "content": "Soybean trypsin inhibitor (SBI) was found to inhibit transformation of human lymphocytes induced by mitogens (leucoagglutinin, concanavalin A, NaIO4) or in mixed lymphocyte reaction (MLR). SBI covalently cross-linked to Sepharose beads inhibited the MLR and mitogen stimulation virtually completely. We have confirmed the work of others which showed that the synthetic anti-proteases epilson-aminocaproic acid and tosyl-L-lysyl-chloromethane (TLCK) also inhibited mitogen-induced blastogenesis and we have shown that phenylmethylsulfonylfluride was effective also; all of these agents were found to inhibit the MLR as well. SBI and TLCK were most inhibitory when added along with mitogen or when mixing allogeneic cells in a MLR; significant decrease in inhibition was noted when TLCK was added 1 h after mitogen. These data support the hypothesis that protease action at a cell surface is an essential early event common to all types of lymphocyte transformation.", "contents": "Inhibition of lymphocyte transformation: effect of soy bean trypsin inhibitor and synthetic anti-proteases. Soybean trypsin inhibitor (SBI) was found to inhibit transformation of human lymphocytes induced by mitogens (leucoagglutinin, concanavalin A, NaIO4) or in mixed lymphocyte reaction (MLR). SBI covalently cross-linked to Sepharose beads inhibited the MLR and mitogen stimulation virtually completely. We have confirmed the work of others which showed that the synthetic anti-proteases epilson-aminocaproic acid and tosyl-L-lysyl-chloromethane (TLCK) also inhibited mitogen-induced blastogenesis and we have shown that phenylmethylsulfonylfluride was effective also; all of these agents were found to inhibit the MLR as well. SBI and TLCK were most inhibitory when added along with mitogen or when mixing allogeneic cells in a MLR; significant decrease in inhibition was noted when TLCK was added 1 h after mitogen. These data support the hypothesis that protease action at a cell surface is an essential early event common to all types of lymphocyte transformation."} {"id": "PMID:175900", "title": "On the monomeric structure and proposed regulatory properties of phosphoenolpyruvate carboxykinase of Escherichia coli.", "content": "Phosphoenolpyruvate carboxykinase (ATP:oxaloacetate carboxy-lyase (transphosphorylating)) (EC 4.1.1.49) has been purified to homogeneity from Escherichia coli. The enzyme shows the same molecular weight (ca. 65000) either by sedimentation equilibrium under nondenaturing conditions or by polyacrylamide gel electrophoresis in the presence of detergent, indicating that the enzyme has a monomeric structure. We have confirmed the previous observation that NADH is an inhibitor of this enzyme, but we have failed to detect the previously reported appearance of homotropic cooperativity with respect to substrate binding the presence of this inhibitor. Lack of such homotropic interactions is in harmony with our conclusion that the enzymes is a monomer. Replacement of Mg2+ by Mn2+ in the assay medium lowers the Km for phosphoenolpyruvate by an order of magnitude, but does not affect the characteristics of inhibition by NADH.", "contents": "On the monomeric structure and proposed regulatory properties of phosphoenolpyruvate carboxykinase of Escherichia coli. Phosphoenolpyruvate carboxykinase (ATP:oxaloacetate carboxy-lyase (transphosphorylating)) (EC 4.1.1.49) has been purified to homogeneity from Escherichia coli. The enzyme shows the same molecular weight (ca. 65000) either by sedimentation equilibrium under nondenaturing conditions or by polyacrylamide gel electrophoresis in the presence of detergent, indicating that the enzyme has a monomeric structure. We have confirmed the previous observation that NADH is an inhibitor of this enzyme, but we have failed to detect the previously reported appearance of homotropic cooperativity with respect to substrate binding the presence of this inhibitor. Lack of such homotropic interactions is in harmony with our conclusion that the enzymes is a monomer. Replacement of Mg2+ by Mn2+ in the assay medium lowers the Km for phosphoenolpyruvate by an order of magnitude, but does not affect the characteristics of inhibition by NADH."} {"id": "PMID:175901", "title": "Plasma lipoprotein profile and composition in White Carneau and Show Racer breeds of pigeons.", "content": "Plasma lipoprotein profile and composition in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were investigated while consuming a regular pigeon chow diet free of cholesterol. Plasma was studied by analytical and preparative ultracentrifugation and paper electrophoresis. Lipid composition of each lipoprotein was determined by combined TLC-GLC techniques. The major plasma lipoprotein of both breeds was high density lipoprotein (HDL) with some low density lipoprotein (LDL) and no very low density lipoprotein (VLDL). Cholesterol was mainly found in the HDL in both breeds (71.7%), and no difference was noticed in the total cholesterol content of whole plasma or in various lipoproteins. The LDL fraction in White Carneaux showed a significantly lower (P less than 0.05) percentage of cholesterol esters compared with Show Racers (58.63 +/- 4.9 in White Carneaux vs. 72.12 +/- 2.1 in Show Racers). In LDL, the percentage of the triglyceride concentration in White Carneaux was significantly lower (P less than 0.01) than that of Show Racers while the percentage of protein content in White Carneaux was higher than in Show Racers. No significant differences were observed in fatty acid composition of steryl esters phospholipids, and triglycerides in the lipoprotein fractions of the two breeds. These studies show important differences in the cholesterol esters, protein, and triglyceride content of LDL in the atherosclerosis-susceptible breed of pigeons.", "contents": "Plasma lipoprotein profile and composition in White Carneau and Show Racer breeds of pigeons. Plasma lipoprotein profile and composition in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were investigated while consuming a regular pigeon chow diet free of cholesterol. Plasma was studied by analytical and preparative ultracentrifugation and paper electrophoresis. Lipid composition of each lipoprotein was determined by combined TLC-GLC techniques. The major plasma lipoprotein of both breeds was high density lipoprotein (HDL) with some low density lipoprotein (LDL) and no very low density lipoprotein (VLDL). Cholesterol was mainly found in the HDL in both breeds (71.7%), and no difference was noticed in the total cholesterol content of whole plasma or in various lipoproteins. The LDL fraction in White Carneaux showed a significantly lower (P less than 0.05) percentage of cholesterol esters compared with Show Racers (58.63 +/- 4.9 in White Carneaux vs. 72.12 +/- 2.1 in Show Racers). In LDL, the percentage of the triglyceride concentration in White Carneaux was significantly lower (P less than 0.01) than that of Show Racers while the percentage of protein content in White Carneaux was higher than in Show Racers. No significant differences were observed in fatty acid composition of steryl esters phospholipids, and triglycerides in the lipoprotein fractions of the two breeds. These studies show important differences in the cholesterol esters, protein, and triglyceride content of LDL in the atherosclerosis-susceptible breed of pigeons."} {"id": "PMID:175902", "title": "The carbohydrate composition of human apo low density lipoprotein from normal and type II hyperlipoproteinemic subjects.", "content": "The carbohydrate composition of the apoprotein from low density lipoprotein (LDL) of normal (average LDL cholesterol, 122 mg/100 ml) and type II hyperlipoproteinemic (average LDL cholesterol, 236 mg/100 ml) males was studied using gas-liquid chromatographic analysis of the methul glycoside derivatives. All samples containing detectable sinking pre-beta-lipoprotein were excluded from the study. The apo LDL from both groups of subjects contained mannose, galactose, N-acetyl-glucosamine and N-acetylneuraminic acid. Glucose and fucose were not found while trace quantities of galactosamine were detected. Although the quantities of galactose and N-acetylglycosamine were the same in the two groups, lower quantities of mannose (p less than or equal to 0.01) and N-acetylneuraminic acid (p less than or equal to 0.05) were found in the type II patients as opposed to normal subjects.", "contents": "The carbohydrate composition of human apo low density lipoprotein from normal and type II hyperlipoproteinemic subjects. The carbohydrate composition of the apoprotein from low density lipoprotein (LDL) of normal (average LDL cholesterol, 122 mg/100 ml) and type II hyperlipoproteinemic (average LDL cholesterol, 236 mg/100 ml) males was studied using gas-liquid chromatographic analysis of the methul glycoside derivatives. All samples containing detectable sinking pre-beta-lipoprotein were excluded from the study. The apo LDL from both groups of subjects contained mannose, galactose, N-acetyl-glucosamine and N-acetylneuraminic acid. Glucose and fucose were not found while trace quantities of galactosamine were detected. Although the quantities of galactose and N-acetylglycosamine were the same in the two groups, lower quantities of mannose (p less than or equal to 0.01) and N-acetylneuraminic acid (p less than or equal to 0.05) were found in the type II patients as opposed to normal subjects."} {"id": "PMID:175903", "title": "Androgen and estrogen binding in rat skeletal and perineal muscles.", "content": "Specific in vitro binding of [3H]testosterone (T), 5ALPHA[3H]dihydrotestosterone (DHT), and [3H[estradiol (E2) was demonstrated in the 30 000 X g supernatant (cytosol) of thigh muscles (TM) and of the levator ani - bulbocavernosus muscle complex (LA-BC) by gel filtration through Sephadex G-25 columns. In TM cytosol, T and E2 [are bound with high affinity (Ka = 1.1 X 10(9) M-1, and 2.3 X 10(9) M-1 respectively) whereas DHT binding is of lower affinity (Ka = 5.0 X 10(7) M-1).] In LA-BC cytosol, T, E2, and DHT are bound with high affinity (Ka = 1.9 X 10(9) M-1, 0.3 X 10(9) M-1, and 0.5 X 10(9) M-1, respectively). Competition experiments suggest that the binding of the three hormones (T, E2, and DHT) is due to different proteins. In addition to TM and LA-BC, T and E2 binding was found in other muscles of male and female rats, including gastrocnemius, the pectoralis, diaphragm, and heart.", "contents": "Androgen and estrogen binding in rat skeletal and perineal muscles. Specific in vitro binding of [3H]testosterone (T), 5ALPHA[3H]dihydrotestosterone (DHT), and [3H[estradiol (E2) was demonstrated in the 30 000 X g supernatant (cytosol) of thigh muscles (TM) and of the levator ani - bulbocavernosus muscle complex (LA-BC) by gel filtration through Sephadex G-25 columns. In TM cytosol, T and E2 [are bound with high affinity (Ka = 1.1 X 10(9) M-1, and 2.3 X 10(9) M-1 respectively) whereas DHT binding is of lower affinity (Ka = 5.0 X 10(7) M-1).] In LA-BC cytosol, T, E2, and DHT are bound with high affinity (Ka = 1.9 X 10(9) M-1, 0.3 X 10(9) M-1, and 0.5 X 10(9) M-1, respectively). Competition experiments suggest that the binding of the three hormones (T, E2, and DHT) is due to different proteins. In addition to TM and LA-BC, T and E2 binding was found in other muscles of male and female rats, including gastrocnemius, the pectoralis, diaphragm, and heart."} {"id": "PMID:175904", "title": "Evidence of respiratory tract infection induced by equine herpesvirus, type 2, in the horse.", "content": "Five horses were experimentally exposed to equine herpesvirus 2 strain LK. Two young foals developed chronic pharyngitis (98 and 232 days, respectively). Growth characteristics, cytopathic effects (CPE), inclusion body formation, ether sensitivity, and immunofluorescent analysis indicated that the virus recovered from infected animals was a herpesvirus serologically identical with, or at least antigenically related to EHV-2 strain LK. No significant complement-fixing (CF) or virus-neutralizing (VN) antibody responses were observed in adult horses while both foals demonstrated a rise in CF antibody titer. One of the two foals demonstrated a rise in VN antibody only. The results suggest that EHV-2 virus induced chronic pharyngitis, primarily the result of lymphoid proliferation, with no overt clinical signs.", "contents": "Evidence of respiratory tract infection induced by equine herpesvirus, type 2, in the horse. Five horses were experimentally exposed to equine herpesvirus 2 strain LK. Two young foals developed chronic pharyngitis (98 and 232 days, respectively). Growth characteristics, cytopathic effects (CPE), inclusion body formation, ether sensitivity, and immunofluorescent analysis indicated that the virus recovered from infected animals was a herpesvirus serologically identical with, or at least antigenically related to EHV-2 strain LK. No significant complement-fixing (CF) or virus-neutralizing (VN) antibody responses were observed in adult horses while both foals demonstrated a rise in CF antibody titer. One of the two foals demonstrated a rise in VN antibody only. The results suggest that EHV-2 virus induced chronic pharyngitis, primarily the result of lymphoid proliferation, with no overt clinical signs."} {"id": "PMID:175905", "title": "Enzymic comparisons of the inorganic sulfur metabolism in autotrophic and heterotrophic Thiobacillus ferrooxidans.", "content": "Activities of enzymes which mediate the oxidation of thiosulfate to sulfate and the assimilation of sulfate to sulfide were assayed in various cell-free fractions of Thiobacillus ferrooxidans grown autotrophically on either ferrous iron or thiosulfate or heterotrophically on glucose. There was no activity of the thiosulfate-oxidizing enzyme in extracts of bacteria grown with ferrous iron. Comparable activities for ATP-sulfurylase (EC 2.7.7.4), ADP-sulfurylase (EC 2.7.7.5), and adenylate kinase (EC 2.7.4.3) were found in the bacteria grown autotrophically with either Fe2+ or S2O32- or heterotrophically with glucose.", "contents": "Enzymic comparisons of the inorganic sulfur metabolism in autotrophic and heterotrophic Thiobacillus ferrooxidans. Activities of enzymes which mediate the oxidation of thiosulfate to sulfate and the assimilation of sulfate to sulfide were assayed in various cell-free fractions of Thiobacillus ferrooxidans grown autotrophically on either ferrous iron or thiosulfate or heterotrophically on glucose. There was no activity of the thiosulfate-oxidizing enzyme in extracts of bacteria grown with ferrous iron. Comparable activities for ATP-sulfurylase (EC 2.7.7.4), ADP-sulfurylase (EC 2.7.7.5), and adenylate kinase (EC 2.7.4.3) were found in the bacteria grown autotrophically with either Fe2+ or S2O32- or heterotrophically with glucose."} {"id": "PMID:175906", "title": "Purification of Oidiodendron kalrai proteases.", "content": "Oidiodendron kalrai yeast-phase cells demonstrate proteolytic activity. Some of the proteolytic enzymes of the crude extract were purified by a combination of ammonium sulfate precipitation, Sephadex G-200, and diethylaminoethyl (DEAE) cellulose column chromatography. At least six proteins exhibiting a range of proteolytic activities could be identified by these procedures. Purity of the enzyme fractions obtained from the DEAE-cellulose columns was tested by running polyacrylamide gels.", "contents": "Purification of Oidiodendron kalrai proteases. Oidiodendron kalrai yeast-phase cells demonstrate proteolytic activity. Some of the proteolytic enzymes of the crude extract were purified by a combination of ammonium sulfate precipitation, Sephadex G-200, and diethylaminoethyl (DEAE) cellulose column chromatography. At least six proteins exhibiting a range of proteolytic activities could be identified by these procedures. Purity of the enzyme fractions obtained from the DEAE-cellulose columns was tested by running polyacrylamide gels."} {"id": "PMID:175907", "title": "Lissencephaly.", "content": "The first reported case of lissencephaly resulting from a consanguinous union strengthens the supposition that in some cases, it is transmitted as an autosomal recessive trait. Comparison of this case with a sporadically occurring case of lissencephaly, with different cortical morphology, suggests that lissencephaly may be an example of either varying gene expressivity or genetic heterogeneity. Lissencephaly and pachygyria may eventually be shown to be due to different causes, some inherited, some acquired. The classical examples of lissencephaly are different morphologically from a case in which antenatal cytomegalovirus infection had produced a small smooth brain. This suggests that antenatal viral infections are destructive rather than teratogenic.", "contents": "Lissencephaly. The first reported case of lissencephaly resulting from a consanguinous union strengthens the supposition that in some cases, it is transmitted as an autosomal recessive trait. Comparison of this case with a sporadically occurring case of lissencephaly, with different cortical morphology, suggests that lissencephaly may be an example of either varying gene expressivity or genetic heterogeneity. Lissencephaly and pachygyria may eventually be shown to be due to different causes, some inherited, some acquired. The classical examples of lissencephaly are different morphologically from a case in which antenatal cytomegalovirus infection had produced a small smooth brain. This suggests that antenatal viral infections are destructive rather than teratogenic."} {"id": "PMID:175908", "title": "Peripheral neuropathy in oxalosis. A case report with electron microscopic observations.", "content": "A 61 year old man had chronic renal failure because of oxaluria and renal calculi. Two years before death, while on hemodialysis, he developed severe progressive peripheral neuropathy. At autopsy calcium oxalate crystals were found in the peripheral nerves and other tissues. Nerve lesions included segmental demyelination, axonal degeneration and crystalline deposits within the myelin sheath. Ultrastructurally there were foci of osmiophilic granular material within myelin lamellae and endoneurium, and pleomorphic lamellar bodies in the perinuclear Schwann cell cytoplasm. It is probable that chronic hemodialysis favors the deposition of oxalate in the Schwann cells and the development of neuropathy in patients with primary hyperoxaluria and renal failure.", "contents": "Peripheral neuropathy in oxalosis. A case report with electron microscopic observations. A 61 year old man had chronic renal failure because of oxaluria and renal calculi. Two years before death, while on hemodialysis, he developed severe progressive peripheral neuropathy. At autopsy calcium oxalate crystals were found in the peripheral nerves and other tissues. Nerve lesions included segmental demyelination, axonal degeneration and crystalline deposits within the myelin sheath. Ultrastructurally there were foci of osmiophilic granular material within myelin lamellae and endoneurium, and pleomorphic lamellar bodies in the perinuclear Schwann cell cytoplasm. It is probable that chronic hemodialysis favors the deposition of oxalate in the Schwann cells and the development of neuropathy in patients with primary hyperoxaluria and renal failure."} {"id": "PMID:175909", "title": "Ultrastructural classification of pituitary adenomas.", "content": "Forty-eight surgically removed pituitary adenomas have been investigated by electron microscopy. Distinct differences in fine structural appearances permitted their separation into 5 classes: 1) Growth hormone, (GH)-cell tumors; 2) Prolactin cell tumors; 3) Mixed adenomas composed of GH and prolactin cells; 4) Adrenocorticotrophic-Melanocyte stimulating hormone (ACTH-MSH) cell tumors; 5) Undifferentiated cell adenomas. Densely and sparsely granulated tumors were distinguished within classes 1, 2 and 4. Although these two forms appeared to represent well defined entities, they may be variants of the same tumor differing only in pace of hormone production and/or release. Number and size of secretory granules varied considerably among tumors composed of the same cell type indicating that pituitary tumor classification cannot be based solely on granule morphology. This classification takes into account morphogenesis with emphasis on clinical features and structure-function relationship.", "contents": "Ultrastructural classification of pituitary adenomas. Forty-eight surgically removed pituitary adenomas have been investigated by electron microscopy. Distinct differences in fine structural appearances permitted their separation into 5 classes: 1) Growth hormone, (GH)-cell tumors; 2) Prolactin cell tumors; 3) Mixed adenomas composed of GH and prolactin cells; 4) Adrenocorticotrophic-Melanocyte stimulating hormone (ACTH-MSH) cell tumors; 5) Undifferentiated cell adenomas. Densely and sparsely granulated tumors were distinguished within classes 1, 2 and 4. Although these two forms appeared to represent well defined entities, they may be variants of the same tumor differing only in pace of hormone production and/or release. Number and size of secretory granules varied considerably among tumors composed of the same cell type indicating that pituitary tumor classification cannot be based solely on granule morphology. This classification takes into account morphogenesis with emphasis on clinical features and structure-function relationship."} {"id": "PMID:175912", "title": "A normal adult and fetal lung antigen present at different quantitative levels in different histologic types of human lung cancer.", "content": "Rabbits were immunized with extract of either an adenocarcinoma of the lung, or one of three oat cell carcinomas of the lung. Unabsorbed and variously absorbed antisera, and various extracts, were analyzed by double and radial immunodiffusion. The adenocarcinomas-antisera identified an antigen subsequently quantitated at high concentration in seven adenocarcinomas of the lung, but a low concentration in five normal adult and four fetal lungs. Three of four epidermoid carcinomas of the lung contained the antigen at low concentration, however only trace amounts were detected in four of five oat cell carcinomas of the lung. The oat cell carcinoma-antisera failed to identify a significant antigen. Quantitatively, the above antigen appeared to distinguish adenocarcinomas and to a lesser extent epidermoid carcinomas from oat cell carcinomas of the lung, and to be consistent with the concept that oat cell carcinomas arise from a different cell type than the other lung tumors.", "contents": "A normal adult and fetal lung antigen present at different quantitative levels in different histologic types of human lung cancer. Rabbits were immunized with extract of either an adenocarcinoma of the lung, or one of three oat cell carcinomas of the lung. Unabsorbed and variously absorbed antisera, and various extracts, were analyzed by double and radial immunodiffusion. The adenocarcinomas-antisera identified an antigen subsequently quantitated at high concentration in seven adenocarcinomas of the lung, but a low concentration in five normal adult and four fetal lungs. Three of four epidermoid carcinomas of the lung contained the antigen at low concentration, however only trace amounts were detected in four of five oat cell carcinomas of the lung. The oat cell carcinoma-antisera failed to identify a significant antigen. Quantitatively, the above antigen appeared to distinguish adenocarcinomas and to a lesser extent epidermoid carcinomas from oat cell carcinomas of the lung, and to be consistent with the concept that oat cell carcinomas arise from a different cell type than the other lung tumors."} {"id": "PMID:175913", "title": "Signet-ring cell carcinoma of the breast. The mucinous variant of infiltrating lobular carcinoma?", "content": "Five cases of the type of mammary carcinoma that has been designated \"signet-ring cell carcinoma\" are presented. This tumor is characterized by the presence of numerous cells containing intracellular mucin, without large amounts of extracellular mucin as is seen in colloid (gelatinous, mucinous) carcinoma of the breast. Although such cells may be seen in many mammary carcinomas, they are never as frequent as in the variant described. Ultrastructurally, the most characteristic finding is the presence of numerous intracellular lumina containing material which appears to represent the mucin identified with the light microscope. This finding differs from that in colloid carcinoma, in which the scantier intracellular mucin occurs in the form of intracytoplasmic membrane-bound vesicles. The five tumors in the present series were all associated with either in situ lobular carcinoma or a \"sinus catarrh\"-like pattern of nodal metastases, or both. On the basis of these light and electron microscopic data, the signet-ring cell carcinoma is suggested as a variant of infiltrating lobular carcinoma, clinically and pathologically distinct from colloid carcinoma.", "contents": "Signet-ring cell carcinoma of the breast. The mucinous variant of infiltrating lobular carcinoma? Five cases of the type of mammary carcinoma that has been designated \"signet-ring cell carcinoma\" are presented. This tumor is characterized by the presence of numerous cells containing intracellular mucin, without large amounts of extracellular mucin as is seen in colloid (gelatinous, mucinous) carcinoma of the breast. Although such cells may be seen in many mammary carcinomas, they are never as frequent as in the variant described. Ultrastructurally, the most characteristic finding is the presence of numerous intracellular lumina containing material which appears to represent the mucin identified with the light microscope. This finding differs from that in colloid carcinoma, in which the scantier intracellular mucin occurs in the form of intracytoplasmic membrane-bound vesicles. The five tumors in the present series were all associated with either in situ lobular carcinoma or a \"sinus catarrh\"-like pattern of nodal metastases, or both. On the basis of these light and electron microscopic data, the signet-ring cell carcinoma is suggested as a variant of infiltrating lobular carcinoma, clinically and pathologically distinct from colloid carcinoma."} {"id": "PMID:175914", "title": "Congenital anomalies among children born of mothers receiving chemotherapy for gestational trophoblastic neoplasms.", "content": "Fifty-eight women who conceived following successful chemotherapy of gestational trophoblastic neoplasms subsequently became pregnant a total of 96 times. Seventy-eight of these 96 pregnancies or 81% terminated in live-born infants. Fifteen of the 96 or 16% ended in abortion and three or 3% terminated with stillborn infants. Among the live-born and stillborn infants there were three with congenital malformations classified as major. While this incidence of congenital malformations does not appear to be increased over that expected, the numbers are too small to perceive a two-fold increase in the expected incidence. Suggestions are made for improvements in the quality of these data.", "contents": "Congenital anomalies among children born of mothers receiving chemotherapy for gestational trophoblastic neoplasms. Fifty-eight women who conceived following successful chemotherapy of gestational trophoblastic neoplasms subsequently became pregnant a total of 96 times. Seventy-eight of these 96 pregnancies or 81% terminated in live-born infants. Fifteen of the 96 or 16% ended in abortion and three or 3% terminated with stillborn infants. Among the live-born and stillborn infants there were three with congenital malformations classified as major. While this incidence of congenital malformations does not appear to be increased over that expected, the numbers are too small to perceive a two-fold increase in the expected incidence. Suggestions are made for improvements in the quality of these data."} {"id": "PMID:175915", "title": "Growth hormone deficiency in children with brain tumors.", "content": "Nine children with brain tumors are described who have received various combinations of treatment, including surgery, radiotherapy, and chemotherapy. Many of the children were noted to be of short stature. Endocrine assessment was carried out from 2 to 10 years after treatment. The combined results of insulin tolerance and Bovril stimulation tests show an impaired growth hormone response in six of the nine children. Bone age is retarded in all cases, and the present height is below the 10th percentile in five of the six. The cause of this growth hormone deficiency is obscure, but further studies are in progress.", "contents": "Growth hormone deficiency in children with brain tumors. Nine children with brain tumors are described who have received various combinations of treatment, including surgery, radiotherapy, and chemotherapy. Many of the children were noted to be of short stature. Endocrine assessment was carried out from 2 to 10 years after treatment. The combined results of insulin tolerance and Bovril stimulation tests show an impaired growth hormone response in six of the nine children. Bone age is retarded in all cases, and the present height is below the 10th percentile in five of the six. The cause of this growth hormone deficiency is obscure, but further studies are in progress."} {"id": "PMID:175917", "title": "The epidemiology of avian lymphoid leukosis.", "content": "Avian lymphoid leukosis can be induced by lymphoid leukosis viruses belonging to Subgroups A, B, C, and D. The endogenous virus of the chicken (Rous-associated virus type 0) belongs to Subgroup E and has little, if any, potential for inducing lymphoid leukosis. Nearly all chicken flocks are infected with Subgroup A lymphoid leukosis virus. This virus can be transmitted from dam to offspring or by contact with infected birds. Early infection, either by congential means, or soon after hatching, leads to the highest incidence of lymphoid leukosis. Maternal antibody or genetic resistance to infection delays or prevents infection, leading to a lower incidence of disease. In flocks segregating for genetic resistance to infection, continued infection is maintained through dynamic interactions between genetic resistance, acquired or maternal antibody ,and virus infection. Expression of endogenous viral information is controlled by dominant genes, but spontaneously produced Rous-associated virus type 0 can spread through a susceptible flock and be transmitted like an exogenous virus.", "contents": "The epidemiology of avian lymphoid leukosis. Avian lymphoid leukosis can be induced by lymphoid leukosis viruses belonging to Subgroups A, B, C, and D. The endogenous virus of the chicken (Rous-associated virus type 0) belongs to Subgroup E and has little, if any, potential for inducing lymphoid leukosis. Nearly all chicken flocks are infected with Subgroup A lymphoid leukosis virus. This virus can be transmitted from dam to offspring or by contact with infected birds. Early infection, either by congential means, or soon after hatching, leads to the highest incidence of lymphoid leukosis. Maternal antibody or genetic resistance to infection delays or prevents infection, leading to a lower incidence of disease. In flocks segregating for genetic resistance to infection, continued infection is maintained through dynamic interactions between genetic resistance, acquired or maternal antibody ,and virus infection. Expression of endogenous viral information is controlled by dominant genes, but spontaneously produced Rous-associated virus type 0 can spread through a susceptible flock and be transmitted like an exogenous virus."} {"id": "PMID:175918", "title": "The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice.", "content": "In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.", "contents": "The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice. In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies."} {"id": "PMID:175919", "title": "Biology of feline leukemia virus in the natural environment.", "content": "The feline leukemia virus (FeLV) was discovered in 1964 in a cluster of cats with lymphosarcoma. The observed clustering of cases of feline lymphosarcoma suggested that FeLV was an infectious agent for cats. The development of a simple immunofluorescent test for FeLV permitted a seroepidemiological study to be undertaken on the distribution of the virus in cats living in their natural environment. Over 2000 cats were tested, and the results showed conclusively that FeLV is an infectious agent for cats. This finding has now been independently confirmed using three different test procedures. After the infectious nature of FeLV was discovered, a simple FeLV test and removal program was devised to control the spread of the virus in the natural environment. The spread of FeLV was controlled in 45 households by removing the FeLV-infected cats, while in 25 households, where the infected cats were left in contact with the uninfected cats, 12% of the uninfected cats became infected. The ultimate control of FeLV awaits the development of an effective FeLV vaccine, which now seems feasible since we have already experimentally immunized some cats with attenuated FeLV. Although FeLV is infectious for cats there is no evidence that FeLV can infect humans.", "contents": "Biology of feline leukemia virus in the natural environment. The feline leukemia virus (FeLV) was discovered in 1964 in a cluster of cats with lymphosarcoma. The observed clustering of cases of feline lymphosarcoma suggested that FeLV was an infectious agent for cats. The development of a simple immunofluorescent test for FeLV permitted a seroepidemiological study to be undertaken on the distribution of the virus in cats living in their natural environment. Over 2000 cats were tested, and the results showed conclusively that FeLV is an infectious agent for cats. This finding has now been independently confirmed using three different test procedures. After the infectious nature of FeLV was discovered, a simple FeLV test and removal program was devised to control the spread of the virus in the natural environment. The spread of FeLV was controlled in 45 households by removing the FeLV-infected cats, while in 25 households, where the infected cats were left in contact with the uninfected cats, 12% of the uninfected cats became infected. The ultimate control of FeLV awaits the development of an effective FeLV vaccine, which now seems feasible since we have already experimentally immunized some cats with attenuated FeLV. Although FeLV is infectious for cats there is no evidence that FeLV can infect humans."} {"id": "PMID:175920", "title": "Immune response to oncornaviruses and tumor-associated antigens in the chicken.", "content": "Two principal virus-directed antigens have been identified on the surface of oncornavirus-infected chick embryo cells. One is identical with the major virus type-specific envelope antigen, which is a glycoprotein with a molecular weight of 85,000. The 2nd antigen (tumor-specific cell surface antigen) is specific for transformed cells, i.e., absent from productively infected but nontransformed cells. This antigen has been identified as a glycoprotein with a molecular weight of 100,000 and was not found in the mature virion. Remarkably, both antigens induce humoral as well as cellular immunity in the chicken. It could be shown that cells can be killed in cytotoxic assays via either the tumor-specific cell surface antigen or the virus envelope glycoprotein alone.", "contents": "Immune response to oncornaviruses and tumor-associated antigens in the chicken. Two principal virus-directed antigens have been identified on the surface of oncornavirus-infected chick embryo cells. One is identical with the major virus type-specific envelope antigen, which is a glycoprotein with a molecular weight of 85,000. The 2nd antigen (tumor-specific cell surface antigen) is specific for transformed cells, i.e., absent from productively infected but nontransformed cells. This antigen has been identified as a glycoprotein with a molecular weight of 100,000 and was not found in the mature virion. Remarkably, both antigens induce humoral as well as cellular immunity in the chicken. It could be shown that cells can be killed in cytotoxic assays via either the tumor-specific cell surface antigen or the virus envelope glycoprotein alone."} {"id": "PMID:175921", "title": "Physiopathology of human and virus-induced murine leukemias.", "content": "The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoietic proliferation and maturation is accompanied by a marked cell loss and provokes enlargement of the stem cell compartment. The so-called leukemic cells have a limited proliferation capacity and may not be truly malignant as opposed to blastic cells in acute leukemias. Clinical, hematological, and physiopathological data that are presently available in chronic granulocytic leukemia, polycythemia vera, and the erythroblastic component of erythroleukemia are compatible with the Friend physiopathological model. It is suggested that these differentiated leukemias initiate from an uncontrolled differentiation of a committed cell compartment, which stimulates proliferation of the stem cell compartment. The disease would be due to a proliferation and accumulation of \"subnormal\" cells characterized by a shorter mean life-span than the normal differentiated cell population. Although limited, the data available suggest that the physiopathology of acute leukemias is clearly distinguishable from that of differentiated leukemias; several immunological and therapeutic applications of this model are outlined.", "contents": "Physiopathology of human and virus-induced murine leukemias. The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoietic proliferation and maturation is accompanied by a marked cell loss and provokes enlargement of the stem cell compartment. The so-called leukemic cells have a limited proliferation capacity and may not be truly malignant as opposed to blastic cells in acute leukemias. Clinical, hematological, and physiopathological data that are presently available in chronic granulocytic leukemia, polycythemia vera, and the erythroblastic component of erythroleukemia are compatible with the Friend physiopathological model. It is suggested that these differentiated leukemias initiate from an uncontrolled differentiation of a committed cell compartment, which stimulates proliferation of the stem cell compartment. The disease would be due to a proliferation and accumulation of \"subnormal\" cells characterized by a shorter mean life-span than the normal differentiated cell population. Although limited, the data available suggest that the physiopathology of acute leukemias is clearly distinguishable from that of differentiated leukemias; several immunological and therapeutic applications of this model are outlined."} {"id": "PMID:175922", "title": "An approach to C-type virus immunoprevention of spontaneously occurring tumors in laboratory mice.", "content": "A review of our current progress in C-type virus vaccine research is presented. This includes the findings of C-type virus or its antigen expressions in every naturally occurring tumor of two strains of \"low-incidence\" laboratory mice, the BALB/cCr mouse and the NIH Swiss mouse. Vaccine preparation methods are described including the inactivation of C-type virus infectivity with optimal maintenance of the antigen titers of at least two of the polypeptides of the C-type virus, gp69/71 and p30. The cell-mediated immune response of the mouse to C-type virus vaccines, as measured by a footpad assay for delayed-type hypersensitivity and an in vitro lymphocyte transformation assay, is described. Studies with two murine C-type viruses (Rauscher leukemia and Gross leukemia) a simian C-type virus, and an avian C-type virus (avian myeloblastosis virus) showed that the cell-mediated immune response of the animal includes type-specific, group-specific, and interspecies-specific reactivity. The mouse gave a cell-mediated immune response to at least one of the polypeptides of the C-type virus, the gp69/71, whether this polypeptide was presented to the immune system of the mouse as whole virus, Tween-ether-treated virus, or a purified polypeptide. One measure of the effectiveness of the C-type virus vaccines was provided by immunization of the mouse with Rauscher leukemia virus preparation that induced resistance to challenge with both live Rauscher leukemia virus and a naturally occurring BALB/c leukemia virus. Evidence is presented that the C-type virus can act as an effective transplantation antigen in syngeneic tumor cell lines resulting in the immunogenicity and loss of tumorigenicity of these cell lines. An approach to the viral immunoprevention of spontaneously occurring tumors is discussed.", "contents": "An approach to C-type virus immunoprevention of spontaneously occurring tumors in laboratory mice. A review of our current progress in C-type virus vaccine research is presented. This includes the findings of C-type virus or its antigen expressions in every naturally occurring tumor of two strains of \"low-incidence\" laboratory mice, the BALB/cCr mouse and the NIH Swiss mouse. Vaccine preparation methods are described including the inactivation of C-type virus infectivity with optimal maintenance of the antigen titers of at least two of the polypeptides of the C-type virus, gp69/71 and p30. The cell-mediated immune response of the mouse to C-type virus vaccines, as measured by a footpad assay for delayed-type hypersensitivity and an in vitro lymphocyte transformation assay, is described. Studies with two murine C-type viruses (Rauscher leukemia and Gross leukemia) a simian C-type virus, and an avian C-type virus (avian myeloblastosis virus) showed that the cell-mediated immune response of the animal includes type-specific, group-specific, and interspecies-specific reactivity. The mouse gave a cell-mediated immune response to at least one of the polypeptides of the C-type virus, the gp69/71, whether this polypeptide was presented to the immune system of the mouse as whole virus, Tween-ether-treated virus, or a purified polypeptide. One measure of the effectiveness of the C-type virus vaccines was provided by immunization of the mouse with Rauscher leukemia virus preparation that induced resistance to challenge with both live Rauscher leukemia virus and a naturally occurring BALB/c leukemia virus. Evidence is presented that the C-type virus can act as an effective transplantation antigen in syngeneic tumor cell lines resulting in the immunogenicity and loss of tumorigenicity of these cell lines. An approach to the viral immunoprevention of spontaneously occurring tumors is discussed."} {"id": "PMID:175923", "title": "Epstein-Barr virus-malaria interaction models for Burkitt's lymphoma: implications for preventive trials.", "content": "Infections with both Epstein-Barr virus (EBV) and malaria have been implicated as causal factors in the pathogenesis of Burkitt's lymphoma (BL). Proposed trials of preventive measures for both infections are receiving serious consideration as possible means of establishing a causal relationship with BL. In this paper we examine certain models for the interaction of EBV and malaria in the induction of BL, and also review the aims of the longitudinal, population-based study being conducted in the West Nile District of Uganda. Given existing knowledge, the outcome of preventive trials, even for the most simple interaction models, is unpredictable and, under certain circumstances, trials of an EBV vaccine could actually increase the incidence of BL. It is suggested that trials of an EBV vaccine at this time would be premature and should be delayed at least until the results from the West Nile prospective study are clear.", "contents": "Epstein-Barr virus-malaria interaction models for Burkitt's lymphoma: implications for preventive trials. Infections with both Epstein-Barr virus (EBV) and malaria have been implicated as causal factors in the pathogenesis of Burkitt's lymphoma (BL). Proposed trials of preventive measures for both infections are receiving serious consideration as possible means of establishing a causal relationship with BL. In this paper we examine certain models for the interaction of EBV and malaria in the induction of BL, and also review the aims of the longitudinal, population-based study being conducted in the West Nile District of Uganda. Given existing knowledge, the outcome of preventive trials, even for the most simple interaction models, is unpredictable and, under certain circumstances, trials of an EBV vaccine could actually increase the incidence of BL. It is suggested that trials of an EBV vaccine at this time would be premature and should be delayed at least until the results from the West Nile prospective study are clear."} {"id": "PMID:175924", "title": "Experimental models for DNA-RNA viral interactions: a brief review.", "content": "Evidences that demonstrate or imply the occurrence of DNA-RNA viral interactions in man and animals are reviewed. The concurrent presence of two dissimilar oncogenic viruses influenced responses both in vivo and in vitro. Cell-mediated immune responses to Marek's disease herpesvirus were altered in specific-pathogen-free chickens inoculated as embryos with an avian leukosis virus. The possible roles of immunological factors in the pathogenesis and control of tumor development associated with DNA-RNA viral interactions remain to be investigated.", "contents": "Experimental models for DNA-RNA viral interactions: a brief review. Evidences that demonstrate or imply the occurrence of DNA-RNA viral interactions in man and animals are reviewed. The concurrent presence of two dissimilar oncogenic viruses influenced responses both in vivo and in vitro. Cell-mediated immune responses to Marek's disease herpesvirus were altered in specific-pathogen-free chickens inoculated as embryos with an avian leukosis virus. The possible roles of immunological factors in the pathogenesis and control of tumor development associated with DNA-RNA viral interactions remain to be investigated."} {"id": "PMID:175925", "title": "Biochemical approaches to detection of Epstein-Barr virus in human tumors.", "content": "The application of biochemical studies for the detection of Epstein-Barr virus (EBV)-DNA in human tumor cells is discussed. These studies resulted in the consistent demonstration of viral nucleic acid in African Burkitt's lymphoma biopsies and in epithelial tumor cells of nasopharyngeal carcinomas. The viral DNA resides within those cells regularly in multiple copies per cell. Besides these tumors our group detected significant concentrations of EBV-DNA in a German lymphoma patient revealing histological characteristics of Burkitt's lymphoma. Moreover, virus DNA was also found in a patient suffering from immunoblastic lymphadenopathy. More than 50 additional B-cell lymphomas and more than 40 biopsies from patients with Hodgkin's disease did not contain detectable amounts of EBV-DNA when tested by nucleic acid hybridization. A tentative scheme of EBV-induced pathogenesis is discussed.", "contents": "Biochemical approaches to detection of Epstein-Barr virus in human tumors. The application of biochemical studies for the detection of Epstein-Barr virus (EBV)-DNA in human tumor cells is discussed. These studies resulted in the consistent demonstration of viral nucleic acid in African Burkitt's lymphoma biopsies and in epithelial tumor cells of nasopharyngeal carcinomas. The viral DNA resides within those cells regularly in multiple copies per cell. Besides these tumors our group detected significant concentrations of EBV-DNA in a German lymphoma patient revealing histological characteristics of Burkitt's lymphoma. Moreover, virus DNA was also found in a patient suffering from immunoblastic lymphadenopathy. More than 50 additional B-cell lymphomas and more than 40 biopsies from patients with Hodgkin's disease did not contain detectable amounts of EBV-DNA when tested by nucleic acid hybridization. A tentative scheme of EBV-induced pathogenesis is discussed."} {"id": "PMID:175926", "title": "Natural mechanisms of controlling lymphotropic herpesvirus infection (Marek's disease) in the chicken.", "content": "Four categories of natural resistance phenomena against Mareks disease in chickens, i.e., maternal antibody, age resistance, genetic resistance, and natural immunization, are described. In nature, these forms of resistance probably act in concert through comlex interrelationships. The mechanisms are not well understood but include humoral immunity (maternal antibody), cell-mediated immunity, and possibly other mechanisms. The possible role of newly discovered tumor-specific antigens in cell-mediated immunity against Marek's disease lymphomas is discussed.", "contents": "Natural mechanisms of controlling lymphotropic herpesvirus infection (Marek's disease) in the chicken. Four categories of natural resistance phenomena against Mareks disease in chickens, i.e., maternal antibody, age resistance, genetic resistance, and natural immunization, are described. In nature, these forms of resistance probably act in concert through comlex interrelationships. The mechanisms are not well understood but include humoral immunity (maternal antibody), cell-mediated immunity, and possibly other mechanisms. The possible role of newly discovered tumor-specific antigens in cell-mediated immunity against Marek's disease lymphomas is discussed."} {"id": "PMID:175927", "title": "Immune response of monkeys to lymphotrophic herpesvirus antigens.", "content": "Herpesvirus saimiri induces leukemia and/or malignant lymphoma when inoculated into different species of nonhuman primates including marmosets and owl monkeys. No malignant disease, however, has been recognized in the natural host for this virus, the squirrel monkey, although a high percentage of these monkeys are chronically infected with H. saimiri. Furthermore, one species of marmosets, as well as capuchin and some owl monkeys, fail to develop lymphoma following experimental virus infection but developed a chronic infection similar to that noted in the natural host. The availability of susceptible and resistant species made it possible to attempt to delineate those humoral and cellular immune parameters that might correlate both with tumor induction and resistance. The findings from these investigations are reviewed and discussed in relation to vaccine studies in this system as a model for a human herpesvirus vaccine.", "contents": "Immune response of monkeys to lymphotrophic herpesvirus antigens. Herpesvirus saimiri induces leukemia and/or malignant lymphoma when inoculated into different species of nonhuman primates including marmosets and owl monkeys. No malignant disease, however, has been recognized in the natural host for this virus, the squirrel monkey, although a high percentage of these monkeys are chronically infected with H. saimiri. Furthermore, one species of marmosets, as well as capuchin and some owl monkeys, fail to develop lymphoma following experimental virus infection but developed a chronic infection similar to that noted in the natural host. The availability of susceptible and resistant species made it possible to attempt to delineate those humoral and cellular immune parameters that might correlate both with tumor induction and resistance. The findings from these investigations are reviewed and discussed in relation to vaccine studies in this system as a model for a human herpesvirus vaccine."} {"id": "PMID:175928", "title": "Preventive vaccination against Herpesvirus saimiri-induced neoplasia.", "content": "In this paper we discuss the use of Herpesvirus saimiri as a model for the development of vaccines against herpesvirus-induced neoplasia in primates. Attempts at protection against the oncogenicity of H. saimiri have centered on the inactivation of virus by heat and formalin, the production of temperature-sensitive H. saimiri mutants, and the attenuation of the virus. Each of these approaches has provided information of use in the development of vaccines that may possibly be used in man.", "contents": "Preventive vaccination against Herpesvirus saimiri-induced neoplasia. In this paper we discuss the use of Herpesvirus saimiri as a model for the development of vaccines against herpesvirus-induced neoplasia in primates. Attempts at protection against the oncogenicity of H. saimiri have centered on the inactivation of virus by heat and formalin, the production of temperature-sensitive H. saimiri mutants, and the attenuation of the virus. Each of these approaches has provided information of use in the development of vaccines that may possibly be used in man."} {"id": "PMID:175929", "title": "Vaccination of nonhuman primates with killed oncogenic herpesviruses.", "content": "Killed herpesvirus cancer vaccines were prepared by inactivation of oncogenic herpesviruses (Herpesvirus saimiri and Herpesvirus ateles) with heat and formaldehyde. The killed vaccines, which are not free of viral nucleic acid, were safe in 121 vaccinated monkeys of 4 different species. Some of these monkeys have now been under observation for 2 years. The vaccines induced high titers of specific humoral antibodies in all vaccinated monkeys. The killed vaccines proved to be efficient against the i.m. challenge with cell-free oncogenic herpesviruses. The challenged animals remained clinically well without signs of an infection and have now been under observation for 1 year, while the nonvaccinated control monkeys died of malignant lymphoma 34 to 52 days after inoculation. The protection against H. saimiri could be passively transmitted with the serum of the vaccinated monkeys. The vaccination did not prevent but delayed tumor development after tumor cell transplantation. The resistance against the oropharyngeal route of infection remains to be determined.", "contents": "Vaccination of nonhuman primates with killed oncogenic herpesviruses. Killed herpesvirus cancer vaccines were prepared by inactivation of oncogenic herpesviruses (Herpesvirus saimiri and Herpesvirus ateles) with heat and formaldehyde. The killed vaccines, which are not free of viral nucleic acid, were safe in 121 vaccinated monkeys of 4 different species. Some of these monkeys have now been under observation for 2 years. The vaccines induced high titers of specific humoral antibodies in all vaccinated monkeys. The killed vaccines proved to be efficient against the i.m. challenge with cell-free oncogenic herpesviruses. The challenged animals remained clinically well without signs of an infection and have now been under observation for 1 year, while the nonvaccinated control monkeys died of malignant lymphoma 34 to 52 days after inoculation. The protection against H. saimiri could be passively transmitted with the serum of the vaccinated monkeys. The vaccination did not prevent but delayed tumor development after tumor cell transplantation. The resistance against the oropharyngeal route of infection remains to be determined."} {"id": "PMID:175930", "title": "Experimental infection of squirrel and marmoset monkeys with attenuated Herpesvirus saimiri.", "content": "Herpesvirus saimiri (HVS) was propagated in vero cells for 3 passages at 39 degrees and cloned 3 times at 34 degrees. This virus was inoculated into cotton-topped marmoset and squirrel monkeys; all inoculated monkeys became infected as HVS was reisolated after their circulating lymphocytes were cultured with vero cells and measurable levels of antiviral antibodies developed that were measured by immunofluorescence and/or neutralization tests. None of the inoculated monkeys developed any signs of overt disease and all inoculated monkeys have survived 9 to 14 months postinoculation. The attenuated virus appears to be genetically stable as virus isolated from an infected marmoset was passed 3 times in vitro and then inoculated into other marmosets, which became infected and remained clinically well. Marmosets latently infected with attenuated HVS were not protected when challenged with a large dose (770 plaque-forming units) of oncogenic HVS, although these marmosets survived about 3 times longer than did inoculated control marmosets.", "contents": "Experimental infection of squirrel and marmoset monkeys with attenuated Herpesvirus saimiri. Herpesvirus saimiri (HVS) was propagated in vero cells for 3 passages at 39 degrees and cloned 3 times at 34 degrees. This virus was inoculated into cotton-topped marmoset and squirrel monkeys; all inoculated monkeys became infected as HVS was reisolated after their circulating lymphocytes were cultured with vero cells and measurable levels of antiviral antibodies developed that were measured by immunofluorescence and/or neutralization tests. None of the inoculated monkeys developed any signs of overt disease and all inoculated monkeys have survived 9 to 14 months postinoculation. The attenuated virus appears to be genetically stable as virus isolated from an infected marmoset was passed 3 times in vitro and then inoculated into other marmosets, which became infected and remained clinically well. Marmosets latently infected with attenuated HVS were not protected when challenged with a large dose (770 plaque-forming units) of oncogenic HVS, although these marmosets survived about 3 times longer than did inoculated control marmosets."} {"id": "PMID:175931", "title": "Implications of a vaccine for the prevention of Epstein-Barr virus infection: ethical and logistic considerations.", "content": "Reasons are given for considering that there is sufficiently substantial indirect and circumstantial evidence linking Epstein-Barr (EB) virus to African Burkitt's lymphoma (BL) and nasopharyngeal carcinoma to call for a dynamic new approach to establish a causal role for the virus in these human cancers. It would seem that the only way to do this would be to develop a vaccine, vaccinate a population at risk in a high-tumor-incidence area, and subsequently follow the population for a consequential decrease in tumor incidence. Recent developments in the control of animal herpesvirus-induced malignant tumors by vaccines free of viral nucleic acid make it possible to envisage that a similar vaccine could be developed against EB virus without undue difficulty. Experiments showing the tumor-inducing ability of EB virus in South American subhuman primates have provided an in vivo laboratory system in which to test the safety and efficacy of the vaccine. Trial of the vaccine in human populations could be carried out by testing its ability to protect those at risk from primary EB virus infection accompanied by infectious mononucleosis. Although in world terms BL is not a major health problem, nevertheless African BL provides uniquely favorable conditions in which to test for a causative role for EB virus: high incidence areas are known, the peak tumor incidence is at the age of 5 or 6, and the effects of vaccination on tumor incidence could be assessed within a decade. Should a carcinogenic role for EB virus be demonstrated in African BL, a much longer term program would be called for to extend the vaccine control of infection to areas where EB virus is implicated in the induction of nasopharyngeal carcinoma. Although a high incidence of this tumor is confined to populations of Southern Chinese origin, the very large numbers of such people and the frequency of the tumor among them make this a substantial world health problem and, therefore, worth the cost and effort necessary to develop a vaccine giving life-long immunity and to conduct a program that will take more than a generation to give positive results.", "contents": "Implications of a vaccine for the prevention of Epstein-Barr virus infection: ethical and logistic considerations. Reasons are given for considering that there is sufficiently substantial indirect and circumstantial evidence linking Epstein-Barr (EB) virus to African Burkitt's lymphoma (BL) and nasopharyngeal carcinoma to call for a dynamic new approach to establish a causal role for the virus in these human cancers. It would seem that the only way to do this would be to develop a vaccine, vaccinate a population at risk in a high-tumor-incidence area, and subsequently follow the population for a consequential decrease in tumor incidence. Recent developments in the control of animal herpesvirus-induced malignant tumors by vaccines free of viral nucleic acid make it possible to envisage that a similar vaccine could be developed against EB virus without undue difficulty. Experiments showing the tumor-inducing ability of EB virus in South American subhuman primates have provided an in vivo laboratory system in which to test the safety and efficacy of the vaccine. Trial of the vaccine in human populations could be carried out by testing its ability to protect those at risk from primary EB virus infection accompanied by infectious mononucleosis. Although in world terms BL is not a major health problem, nevertheless African BL provides uniquely favorable conditions in which to test for a causative role for EB virus: high incidence areas are known, the peak tumor incidence is at the age of 5 or 6, and the effects of vaccination on tumor incidence could be assessed within a decade. Should a carcinogenic role for EB virus be demonstrated in African BL, a much longer term program would be called for to extend the vaccine control of infection to areas where EB virus is implicated in the induction of nasopharyngeal carcinoma. Although a high incidence of this tumor is confined to populations of Southern Chinese origin, the very large numbers of such people and the frequency of the tumor among them make this a substantial world health problem and, therefore, worth the cost and effort necessary to develop a vaccine giving life-long immunity and to conduct a program that will take more than a generation to give positive results."} {"id": "PMID:175932", "title": "Pilot studies with human interferon in Herpesvirus saimiri-induced lymphoma in owl monkeys.", "content": "The nature of Herpesvirus saimiri-induced disease in owl monkeys is described with emphasis on those biological parameters useful in monitoring the disease. These parameters are lymphocyte response to general mitogens, lymphocyte-infective centers, and antibody to virus-associated early antigen. Human interferon was used in treating owl monkeys with virus-induced leukemia. In 2 animals evidence was obtained that suggested a positive antileukemic effect.", "contents": "Pilot studies with human interferon in Herpesvirus saimiri-induced lymphoma in owl monkeys. The nature of Herpesvirus saimiri-induced disease in owl monkeys is described with emphasis on those biological parameters useful in monitoring the disease. These parameters are lymphocyte response to general mitogens, lymphocyte-infective centers, and antibody to virus-associated early antigen. Human interferon was used in treating owl monkeys with virus-induced leukemia. In 2 animals evidence was obtained that suggested a positive antileukemic effect."} {"id": "PMID:175933", "title": "Natural immunity in the oncornavirus-infected mouse.", "content": "BALB/cfC3H females neonatally infected with mammary tumor virus (MTV) possess spleen cells capable of significant cytotoxic activity against target MTV-induced mammary tumor cells in microcytotoxicity assay. Spleen cells from supposedly MTV-free BALB/c females are also specifically reactive, as a result of horizontal transmission of MTV antigens. No quantitative differences in reactivity exist between females not susceptible to the development of mammary tumors (BALB/c) and those that may develop or already have tumors (multiparous BALB/cfC3H). However, there are qualitative differences in response between those at risk and those not at risk.", "contents": "Natural immunity in the oncornavirus-infected mouse. BALB/cfC3H females neonatally infected with mammary tumor virus (MTV) possess spleen cells capable of significant cytotoxic activity against target MTV-induced mammary tumor cells in microcytotoxicity assay. Spleen cells from supposedly MTV-free BALB/c females are also specifically reactive, as a result of horizontal transmission of MTV antigens. No quantitative differences in reactivity exist between females not susceptible to the development of mammary tumors (BALB/c) and those that may develop or already have tumors (multiparous BALB/cfC3H). However, there are qualitative differences in response between those at risk and those not at risk."} {"id": "PMID:175934", "title": "Correlation of in vitro and in vivo studies of antigens relevant to the control of murine breast cancer.", "content": "The specific immune response of C3H [mammary tumor virus (MTV)] (MTV+) and C3Hf sublines (MTV- or milk-MTV-) to mammary tumors of C3H origin was measured in vitro by the ability of lymphocytes derived from immunized animals to destroy 3H-proline prelabeled target cells after 36 hr of incubation in vitro (lymphocyte:target ratio, 400:1). Primary cytotoxic responses were obtained both in C3H and C3Hf mice and were mediated mainly by T-lymphocytes (Thy.1-positive cells). The degree of cross-reactivity between different C3H mammary tumors showed wide ranges and actually depended on the amounts of MTV-related antigens expressed in the tumor cells. An inverse relationship between MTV-related and H2 histocompatibility antigens was observed. Thy.1.2 antigen (theta-C3H) was also detected on the surface of mammary tumor cells. Both C3H and C3Hf recognized cross-reacting and noncross-reacting antigens in the tumor cells, although the magnitude of the response in the MTV+ mice was lower than in the C3Hf sublines. Soluble antigens could be extracted by 3 M KCl treatment of the tumor cells and could be used as immunogens (eliciting cytotoxic responses against mammary tumor cells), or as stimulators for thymidine uptake (blast transformation in vitro) for specifically immune T-lymphocytes. Attempts to modify spontaneous tumor development in C3H and C3HfA virgin female mice by immunization with formalinized MTV or with soluble antigens extracted from C3H mammary tumors, although still in progress, showed a moderate preventive effect (especially in the C3HfA) immunized with MTV and an acceleration of tumor appearance both in C3H and C3HfA mice immunized with the soluble antigens extracted from C3H mammary tumors. This last set of results, although preliminary, indicates that a better understanding of the immunological events in this system is essential for the design of experiments on prophylaxis of tumor development.", "contents": "Correlation of in vitro and in vivo studies of antigens relevant to the control of murine breast cancer. The specific immune response of C3H [mammary tumor virus (MTV)] (MTV+) and C3Hf sublines (MTV- or milk-MTV-) to mammary tumors of C3H origin was measured in vitro by the ability of lymphocytes derived from immunized animals to destroy 3H-proline prelabeled target cells after 36 hr of incubation in vitro (lymphocyte:target ratio, 400:1). Primary cytotoxic responses were obtained both in C3H and C3Hf mice and were mediated mainly by T-lymphocytes (Thy.1-positive cells). The degree of cross-reactivity between different C3H mammary tumors showed wide ranges and actually depended on the amounts of MTV-related antigens expressed in the tumor cells. An inverse relationship between MTV-related and H2 histocompatibility antigens was observed. Thy.1.2 antigen (theta-C3H) was also detected on the surface of mammary tumor cells. Both C3H and C3Hf recognized cross-reacting and noncross-reacting antigens in the tumor cells, although the magnitude of the response in the MTV+ mice was lower than in the C3Hf sublines. Soluble antigens could be extracted by 3 M KCl treatment of the tumor cells and could be used as immunogens (eliciting cytotoxic responses against mammary tumor cells), or as stimulators for thymidine uptake (blast transformation in vitro) for specifically immune T-lymphocytes. Attempts to modify spontaneous tumor development in C3H and C3HfA virgin female mice by immunization with formalinized MTV or with soluble antigens extracted from C3H mammary tumors, although still in progress, showed a moderate preventive effect (especially in the C3HfA) immunized with MTV and an acceleration of tumor appearance both in C3H and C3HfA mice immunized with the soluble antigens extracted from C3H mammary tumors. This last set of results, although preliminary, indicates that a better understanding of the immunological events in this system is essential for the design of experiments on prophylaxis of tumor development."} {"id": "PMID:175935", "title": "Implications of humoral antibody in mice and humans to breast tumor and mouse mammary tumor virus-associated antigens.", "content": "As a part of a program directed toward the elucidation of the role of viruses in mouse and human breast cancer, a variety of immunological techniques were applied to a study of the humoral immune response of mice and of humans to their breast tumors. Tumor-bearing mice were found to produce antibodies against a complex array of tumor cell-associated antigens, including mouse mammary tumor virus (MMTV), components, heterophile and Forssman-like antigens, embryonic antigens, and possibly other tumor-associated antigens. Mice bearing MMTV-positive tumors had high titer antibodies against both viral and heterophile antigens. Tumor-free mice, whether of high or low mammary cancer strains, were remarkably free of antibodies that could label MMTV particles, although some sera contained antibodies to viral components. Patients with breast cancer also had antibodies against a variety of antigens associated with their own and homologous breast cancer cells. These antibodies reacted with heterophile, embryonic, and other tumor-associated antigens, some of which appeared to be viral. Sera of some patients with breast cancer gave positive immunofluorescence reactions with mouse mammary tumor cells grown in tissue culture and producing MMTV. Most of these reactions were due to heterophile antibodies in the sera, but a small number of sera contained antibodies apparently directed specifically toward MMTV particles, as determined by immunoperoxidase electron microscopy. Although human-mouse cross-reactions must be interpreted with caution, these data suggest that a virus putatively associated with human breast cancer is antigenically related to MMTV.", "contents": "Implications of humoral antibody in mice and humans to breast tumor and mouse mammary tumor virus-associated antigens. As a part of a program directed toward the elucidation of the role of viruses in mouse and human breast cancer, a variety of immunological techniques were applied to a study of the humoral immune response of mice and of humans to their breast tumors. Tumor-bearing mice were found to produce antibodies against a complex array of tumor cell-associated antigens, including mouse mammary tumor virus (MMTV), components, heterophile and Forssman-like antigens, embryonic antigens, and possibly other tumor-associated antigens. Mice bearing MMTV-positive tumors had high titer antibodies against both viral and heterophile antigens. Tumor-free mice, whether of high or low mammary cancer strains, were remarkably free of antibodies that could label MMTV particles, although some sera contained antibodies to viral components. Patients with breast cancer also had antibodies against a variety of antigens associated with their own and homologous breast cancer cells. These antibodies reacted with heterophile, embryonic, and other tumor-associated antigens, some of which appeared to be viral. Sera of some patients with breast cancer gave positive immunofluorescence reactions with mouse mammary tumor cells grown in tissue culture and producing MMTV. Most of these reactions were due to heterophile antibodies in the sera, but a small number of sera contained antibodies apparently directed specifically toward MMTV particles, as determined by immunoperoxidase electron microscopy. Although human-mouse cross-reactions must be interpreted with caution, these data suggest that a virus putatively associated with human breast cancer is antigenically related to MMTV."} {"id": "PMID:175936", "title": "Biological considerations of tumor-specific and virus-associated antigens of human breast cancers.", "content": "In vivo and in vitro studies bearing on tumor-specific and viral-associated antigenicity of human breast carcinomas were reviewed with particular attention to the following clinical considerations: (a) breast carcinomas arise in a nonrandom fashion; (b) in situ carcinomas precede invasive breast carcinomas; (c) invasive breast carcinomas behave in a heterogeneous fashion. Microscopically demonstrable lymphoreticuloendothelial responses, skin window tests, and leukocyte migration tests all indicate that tumor-specific antigenicity develops in assoication with the early phases of mammary carcinogenesis. Such antigenicity is maximally expressed in in situ carcinomas without associated invasive breast cancer and minimally in invasive breast cancers with metastases. Immunogenic breast cancer tissues commonly contain a protein component the antigenic and physicochemical properties of which are similar to those of a protein component of murine mammary tumor virus. Advances in our understanding and control of human mammary carcinogenesis and biological behavior are dependent on the clinicopathological characterization of individual patients and their breast tissues as well as on the analytical procedures used.", "contents": "Biological considerations of tumor-specific and virus-associated antigens of human breast cancers. In vivo and in vitro studies bearing on tumor-specific and viral-associated antigenicity of human breast carcinomas were reviewed with particular attention to the following clinical considerations: (a) breast carcinomas arise in a nonrandom fashion; (b) in situ carcinomas precede invasive breast carcinomas; (c) invasive breast carcinomas behave in a heterogeneous fashion. Microscopically demonstrable lymphoreticuloendothelial responses, skin window tests, and leukocyte migration tests all indicate that tumor-specific antigenicity develops in assoication with the early phases of mammary carcinogenesis. Such antigenicity is maximally expressed in in situ carcinomas without associated invasive breast cancer and minimally in invasive breast cancers with metastases. Immunogenic breast cancer tissues commonly contain a protein component the antigenic and physicochemical properties of which are similar to those of a protein component of murine mammary tumor virus. Advances in our understanding and control of human mammary carcinogenesis and biological behavior are dependent on the clinicopathological characterization of individual patients and their breast tissues as well as on the analytical procedures used."} {"id": "PMID:175938", "title": "Further immunization studies with mammary tumor virus.", "content": "A single i.m. dose of formalin-inactivated murine mammary tumor virus greatly reduces viral expression and mammary tumorigenesis in Af (tumor incidence, 39%) and RIIIf (tumor incidence, 11%) mice, which carry only endogenous, gamete-transmitted virus. In C57BL mice, 1 mug of vaccine in Freund's complete adjuvant protects against later challenge with RIII virus.", "contents": "Further immunization studies with mammary tumor virus. A single i.m. dose of formalin-inactivated murine mammary tumor virus greatly reduces viral expression and mammary tumorigenesis in Af (tumor incidence, 39%) and RIIIf (tumor incidence, 11%) mice, which carry only endogenous, gamete-transmitted virus. In C57BL mice, 1 mug of vaccine in Freund's complete adjuvant protects against later challenge with RIII virus."} {"id": "PMID:175940", "title": "Human cervical cancer as a venereal disease.", "content": "The operation of venereal factors in human cervical cancer is suggested by demographic and epidemiological data. Recent evidence supporting the genital herpesvirus hypothesis is consistent with this notion. A controlled epidemiological investigation has been undertaken on the role of the male coital partner in cervical carcinogenesis. An answer is sought to the question, \"Is the risk of developing cervical cancer increased among the wives of men who at some other time were married to other women who developed cervical cancer?\" With one-quarter of the study completed, a total of 14 marital clusters have been identified in which 2 or more wives of the same men developed cervical carcinoma. The expected number of such clusters is estimated to be 4.", "contents": "Human cervical cancer as a venereal disease. The operation of venereal factors in human cervical cancer is suggested by demographic and epidemiological data. Recent evidence supporting the genital herpesvirus hypothesis is consistent with this notion. A controlled epidemiological investigation has been undertaken on the role of the male coital partner in cervical carcinogenesis. An answer is sought to the question, \"Is the risk of developing cervical cancer increased among the wives of men who at some other time were married to other women who developed cervical cancer?\" With one-quarter of the study completed, a total of 14 marital clusters have been identified in which 2 or more wives of the same men developed cervical carcinoma. The expected number of such clusters is estimated to be 4."} {"id": "PMID:175941", "title": "Model systems for cervical cancer.", "content": "The evidence suggesting that a venereally transmitted virus and/or hormonal factors are involved in the etiology of cervical cancer is reviewed. The animal models used to test the oncogenic potential of these two types of agents are also discussed.", "contents": "Model systems for cervical cancer. The evidence suggesting that a venereally transmitted virus and/or hormonal factors are involved in the etiology of cervical cancer is reviewed. The animal models used to test the oncogenic potential of these two types of agents are also discussed."} {"id": "PMID:175943", "title": "A search for herpes simplex virus type 2 markers in cervical carcinoma.", "content": "Carcinoma of the uterine cervix is now clearly recognized as the second most common malignant disease of women in the United States. Epidemiological studies provided the first suggestive evidence that an infectious, venereally transmitted agent was involved in this disease in either a causal or a casual fashion. Later cytohistopathological, virological, and seroepidemiological studies confirmed this observation and identified the suspect agent as herpes simplex virus type 2. Recently, several laboratories have directed their energies towards establishing lines of direct evidence linking herpes simplex virus type 2 etiologically with human cervical carcinoma. Some of these approaches have involved attempts to detect infectious virus, viral components, or virus-specific modifications in neoplastic cervical tissues. Results obtained utilizing human tissues will be reviewed and discussed.", "contents": "A search for herpes simplex virus type 2 markers in cervical carcinoma. Carcinoma of the uterine cervix is now clearly recognized as the second most common malignant disease of women in the United States. Epidemiological studies provided the first suggestive evidence that an infectious, venereally transmitted agent was involved in this disease in either a causal or a casual fashion. Later cytohistopathological, virological, and seroepidemiological studies confirmed this observation and identified the suspect agent as herpes simplex virus type 2. Recently, several laboratories have directed their energies towards establishing lines of direct evidence linking herpes simplex virus type 2 etiologically with human cervical carcinoma. Some of these approaches have involved attempts to detect infectious virus, viral components, or virus-specific modifications in neoplastic cervical tissues. Results obtained utilizing human tissues will be reviewed and discussed."} {"id": "PMID:175944", "title": "Experimental evidence for the oncogenic potential of herpes simplex virus.", "content": "The data presented in this review reveal the transforming potential and oncogenic capability of herpes simplex viruses in cultured cells and in experimental animals, respectively. Unfortunately, the role of these agents in human cancer, especially cervical, cannot be unequivocally established through the indirect approaches used, but circumstantial evidence that these viruses represent potential oncogens in the human population is mounting.", "contents": "Experimental evidence for the oncogenic potential of herpes simplex virus. The data presented in this review reveal the transforming potential and oncogenic capability of herpes simplex viruses in cultured cells and in experimental animals, respectively. Unfortunately, the role of these agents in human cancer, especially cervical, cannot be unequivocally established through the indirect approaches used, but circumstantial evidence that these viruses represent potential oncogens in the human population is mounting."} {"id": "PMID:175945", "title": "Herpesvirus type 2-related antigens and their relevance to humoral and cell-mediated immunity in patients with cervical cancer.", "content": "The central theme of this communication is the interaction of herpes simplex virus type 2 with its host. In addition to the productive infection, we are confronted by latency and, as suggested by recent studies, by cancer. The possible mechanisms of latency and the role it may play as a precursor of carcinogenesis are discussed. If virus is to coexist with its host, a defined level of molecular interaction between host and viral gene products must exist. The association of AG-4 with active tumor growth and its identification as a minor virion protein, also exposed on the surface of the infected cell, open new vistas in the understanding of the role virus-host cell interactions may play in tumor growth. The modulation of the host immune response by the results of this interaction may play a significant role in cancer control. In these terms, the observation that antibody to AG-4 is a macroglobulin and that, therefore, immunity to AG-4 may be T-cell independent, should be given further consideration.", "contents": "Herpesvirus type 2-related antigens and their relevance to humoral and cell-mediated immunity in patients with cervical cancer. The central theme of this communication is the interaction of herpes simplex virus type 2 with its host. In addition to the productive infection, we are confronted by latency and, as suggested by recent studies, by cancer. The possible mechanisms of latency and the role it may play as a precursor of carcinogenesis are discussed. If virus is to coexist with its host, a defined level of molecular interaction between host and viral gene products must exist. The association of AG-4 with active tumor growth and its identification as a minor virion protein, also exposed on the surface of the infected cell, open new vistas in the understanding of the role virus-host cell interactions may play in tumor growth. The modulation of the host immune response by the results of this interaction may play a significant role in cancer control. In these terms, the observation that antibody to AG-4 is a macroglobulin and that, therefore, immunity to AG-4 may be T-cell independent, should be given further consideration."} {"id": "PMID:175946", "title": "Studies on herpes simplex virus and cancer.", "content": "Virus-induced polypeptides of cells infected by herpes simplex virus (HSV) types 1 and 2 were investigated by analysis on polyacrylamide gels and by determination of their antigenicity. Some polypeptides, VP154 and VP134, had immunological reactivity common to both virus types, while others (VP175 and VP123) were type specific. Only the glycosylated polypeptides were able to induce neutralizing antibody. The expression of viral genetic information was studied in newborn mice infected with wild-type and ts mutant viruses; some mutants had become attenuated and had lost pathogenicity for newborn mice while others had not. From induction experiments in HSV=transformed hamster cells, it appears that detection of enhanced replication of ts mutants in human cancer cells would be an indication of resident HSV genetic information. Sera obtained from cancer patients were examined for antibodies to early proteins synthesized in HSV-infected cells. The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. Cervical cancer patients had sera with a higher reactivity to early nonstructural polypeptides than to breast cancer patients or to matched healthy women. In contrast to the results with early polypeptides, little difference was detectable between the matched sera in their reactivity with a major capsid polypeptide, which is synthesized late in the infectious cycle.", "contents": "Studies on herpes simplex virus and cancer. Virus-induced polypeptides of cells infected by herpes simplex virus (HSV) types 1 and 2 were investigated by analysis on polyacrylamide gels and by determination of their antigenicity. Some polypeptides, VP154 and VP134, had immunological reactivity common to both virus types, while others (VP175 and VP123) were type specific. Only the glycosylated polypeptides were able to induce neutralizing antibody. The expression of viral genetic information was studied in newborn mice infected with wild-type and ts mutant viruses; some mutants had become attenuated and had lost pathogenicity for newborn mice while others had not. From induction experiments in HSV=transformed hamster cells, it appears that detection of enhanced replication of ts mutants in human cancer cells would be an indication of resident HSV genetic information. Sera obtained from cancer patients were examined for antibodies to early proteins synthesized in HSV-infected cells. The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. Cervical cancer patients had sera with a higher reactivity to early nonstructural polypeptides than to breast cancer patients or to matched healthy women. In contrast to the results with early polypeptides, little difference was detectable between the matched sera in their reactivity with a major capsid polypeptide, which is synthesized late in the infectious cycle."} {"id": "PMID:175949", "title": "Induction of syncytia by the bovine C-type leukemia virus.", "content": "Bovine buffy coat cells infected with the bovine leukemia virus (BLV) induce syncytia formation in human diploid embryonic lung cells as well as in monolayer cell cultures of bovine, simian, ovine, bat, and caprine origin, but not in mouse fibroblast cells, normall rat kidney cells, or RSV-transformed rat cells. Syncytia were not observed in diploid embryonic lung cells inoculated with bovine buffy coat cells free of BLV. The syncytia-induction effect is associated with the synthesis of complete BLV by the buffy coat cells and is independent of whether these cells are viable, disrupted, normal, or malignant. Cell-free preparations of BLV and density gradient-purified virus also induce syncytia when added directly to diploid embryonic lung cells and to bovine, bat, and caprine monolayer cell cultures. Ether treatment, ultraviolet light irradiation, heating, freezing, and thawing destroy the syncytia-inducing activity of BLV. This activity is also neutralized when the virus is incubated with sera containing antibodies to BLV, but not when incubated with sera free of these antibodies or reference serum for the foamy-like bovine syncytial virus. Several other lines of evidence rule out the possibility that this virus or other bovine viruses are responsible for the syncytia-inducing phenomenon described here. BLV antigen was consistently detected by the immunofluorescent test in the syncytia-positive monolayer indicator cultures. However, syncytia formation was not necessarily associated with BLV production by the indicator cells. The ability to induce syncytia in monolayer cultures of nontransformed cells distinguishes BLV from all the known C-type luekemia viruses.", "contents": "Induction of syncytia by the bovine C-type leukemia virus. Bovine buffy coat cells infected with the bovine leukemia virus (BLV) induce syncytia formation in human diploid embryonic lung cells as well as in monolayer cell cultures of bovine, simian, ovine, bat, and caprine origin, but not in mouse fibroblast cells, normall rat kidney cells, or RSV-transformed rat cells. Syncytia were not observed in diploid embryonic lung cells inoculated with bovine buffy coat cells free of BLV. The syncytia-induction effect is associated with the synthesis of complete BLV by the buffy coat cells and is independent of whether these cells are viable, disrupted, normal, or malignant. Cell-free preparations of BLV and density gradient-purified virus also induce syncytia when added directly to diploid embryonic lung cells and to bovine, bat, and caprine monolayer cell cultures. Ether treatment, ultraviolet light irradiation, heating, freezing, and thawing destroy the syncytia-inducing activity of BLV. This activity is also neutralized when the virus is incubated with sera containing antibodies to BLV, but not when incubated with sera free of these antibodies or reference serum for the foamy-like bovine syncytial virus. Several other lines of evidence rule out the possibility that this virus or other bovine viruses are responsible for the syncytia-inducing phenomenon described here. BLV antigen was consistently detected by the immunofluorescent test in the syncytia-positive monolayer indicator cultures. However, syncytia formation was not necessarily associated with BLV production by the indicator cells. The ability to induce syncytia in monolayer cultures of nontransformed cells distinguishes BLV from all the known C-type luekemia viruses."} {"id": "PMID:175950", "title": "Development of an in vitro infectivity assay for the C-type bovine leukemia virus.", "content": "The ability of the bovine C-type leukemia virus to induce syncytia formation in monolayer cell cultures has been used to develop a specific and simple infectivity assay for the virus. Using bovine embryonic spleen cells or human diploid embryonic lung cells as indicator cells, the results of the assay can be evaluated in 4 to 6 or 6 to 8 days, respectively. Pretreatment of the indicator cells with DEAE-dextran greatly increases the sensitivity of the assay. The assay is quantitative and can be applied as a direct method for the identification of bovine C-type leukemia virus-infected animals; it also provides a simple, and sensitive procedure for the detection and titration of virus-neutralizing antibodies.", "contents": "Development of an in vitro infectivity assay for the C-type bovine leukemia virus. The ability of the bovine C-type leukemia virus to induce syncytia formation in monolayer cell cultures has been used to develop a specific and simple infectivity assay for the virus. Using bovine embryonic spleen cells or human diploid embryonic lung cells as indicator cells, the results of the assay can be evaluated in 4 to 6 or 6 to 8 days, respectively. Pretreatment of the indicator cells with DEAE-dextran greatly increases the sensitivity of the assay. The assay is quantitative and can be applied as a direct method for the identification of bovine C-type leukemia virus-infected animals; it also provides a simple, and sensitive procedure for the detection and titration of virus-neutralizing antibodies."} {"id": "PMID:175951", "title": "Surface localization of virus production on a glucocorticoid-stimulated oncornavirus-producing mouse mammary tumor cell line by scanning electron microscopy.", "content": "A chronically infected continuous mouse mammary tumor cell line containing virus particles of type B morphology, free of contaminating type C virions, has been grown in tissue culture. These cells were treated with dexamethasone, a synthetic glucocorticoid, a potent stimulator of mouse mammary tumor virus expression. Surfaces of untreated and dexamethasone-treated cells were investigated by scanning electron microscopy. Untreated cells demonstrated a moderate expression of mouse mammary tumor virus (80 particles/cell) distributed diffusely over the cell surface. However, virions on dexamethasone-treated cells were localized in clusters of 100 to greater than 2000 virus particles, often with more than one cluster per cell. Dexamethasone-treated cells typically showed a 10-fold increase in cell-associated virus over untreated cells. Concentrated extracellular fluids from untreated and dexamethasone-treated cultures were quantitated for free virus. Dexamethasone-treated culture fluids demonstrated a similar 10-fold increase of extracellular particles, in contrast to untreated cultures. This increase in virus particles on the cell surfaces as well as in the extracellular fluids supports the theory that dexamethasone has a stimulatory effect on viral replication, not just on the release of budding particles. The ultrastructure of budding mouse mammary tumor virus during dexamethasone stimulation, determined by scanning and transmission electron microscopy, and the significance of such an in vitro system for viral immunodiagnosis are discussed.", "contents": "Surface localization of virus production on a glucocorticoid-stimulated oncornavirus-producing mouse mammary tumor cell line by scanning electron microscopy. A chronically infected continuous mouse mammary tumor cell line containing virus particles of type B morphology, free of contaminating type C virions, has been grown in tissue culture. These cells were treated with dexamethasone, a synthetic glucocorticoid, a potent stimulator of mouse mammary tumor virus expression. Surfaces of untreated and dexamethasone-treated cells were investigated by scanning electron microscopy. Untreated cells demonstrated a moderate expression of mouse mammary tumor virus (80 particles/cell) distributed diffusely over the cell surface. However, virions on dexamethasone-treated cells were localized in clusters of 100 to greater than 2000 virus particles, often with more than one cluster per cell. Dexamethasone-treated cells typically showed a 10-fold increase in cell-associated virus over untreated cells. Concentrated extracellular fluids from untreated and dexamethasone-treated cultures were quantitated for free virus. Dexamethasone-treated culture fluids demonstrated a similar 10-fold increase of extracellular particles, in contrast to untreated cultures. This increase in virus particles on the cell surfaces as well as in the extracellular fluids supports the theory that dexamethasone has a stimulatory effect on viral replication, not just on the release of budding particles. The ultrastructure of budding mouse mammary tumor virus during dexamethasone stimulation, determined by scanning and transmission electron microscopy, and the significance of such an in vitro system for viral immunodiagnosis are discussed."} {"id": "PMID:175952", "title": "Carcinogenesis by carbamic acid esters and their binding to DNA.", "content": "The tumor-initiating potency of three simple alkyl carbamates and mono-N-substituted ethyl carbamates was examined in Hall strain mice. The binding of 14C-labeled carbamates of DNA was measured in Crackenbush mice. Ethyl carbamate was the most potent carcinogen for the epidermis, liver, and lung, followed by its N-alkyl derivatives. Methyl carbamate was without effect but n-propyl and n-butyl were possible carcinogens. The ethyl esters bound to a greater extent to DNA in liver and skin than the methyl, n-propyl, and n-butyl esters and only this binding persisted. A preliminary application of croton oil increased the yield of skin tumors but not of liver or lung tumors. It also increased the binding of the alkyl carbamates to DNA in skin, the increase being greatest with ethyl carbamate. The binding persisted longer in treated than in non-croton oil-treated mice.", "contents": "Carcinogenesis by carbamic acid esters and their binding to DNA. The tumor-initiating potency of three simple alkyl carbamates and mono-N-substituted ethyl carbamates was examined in Hall strain mice. The binding of 14C-labeled carbamates of DNA was measured in Crackenbush mice. Ethyl carbamate was the most potent carcinogen for the epidermis, liver, and lung, followed by its N-alkyl derivatives. Methyl carbamate was without effect but n-propyl and n-butyl were possible carcinogens. The ethyl esters bound to a greater extent to DNA in liver and skin than the methyl, n-propyl, and n-butyl esters and only this binding persisted. A preliminary application of croton oil increased the yield of skin tumors but not of liver or lung tumors. It also increased the binding of the alkyl carbamates to DNA in skin, the increase being greatest with ethyl carbamate. The binding persisted longer in treated than in non-croton oil-treated mice."} {"id": "PMID:175953", "title": "Receptor characteristics of specific estrogen binding in the renal adenocarcinoma of the golden hamster.", "content": "Linear sucrose gradient analyses reveal that all estrogen-induced and -dependent primary renal tumor cytosols examined contain an 8 S and variable amounts of 4 S receptor in low ionic buffer concentrations. Similar results were obtained with extracts of primary metastases of these tumors. Sucrose gradients containing high salt (0.4 M KCl) convert the 8 S receptor in both the hamster renal tumor and uterus to a 4 to 5 S complex. Scatchard plot analysis reveals that the renal tumor cytosol estradiol-receptor complex has a Ka of 1.7 X 10(9) M-1 and 9.2 X 10(-10) M binding sites. Competition for the tritiated 17beta-estradiol binding sites in the renal tumor was similar to that in the uterus with respect to estrogenic compounds. Nonestrogenic steroids exhibited minimal competition at the same concentrations or higher. Substitution in the ring structure, particularly in position 3 of the phenolic A-ring, resulted in a considerable loss in the ability of such compounds to compete for these receptors. Aniestrogens were effective competitors for these estrogen receptors only at higher concentrations relative to the tritiated estradiol.", "contents": "Receptor characteristics of specific estrogen binding in the renal adenocarcinoma of the golden hamster. Linear sucrose gradient analyses reveal that all estrogen-induced and -dependent primary renal tumor cytosols examined contain an 8 S and variable amounts of 4 S receptor in low ionic buffer concentrations. Similar results were obtained with extracts of primary metastases of these tumors. Sucrose gradients containing high salt (0.4 M KCl) convert the 8 S receptor in both the hamster renal tumor and uterus to a 4 to 5 S complex. Scatchard plot analysis reveals that the renal tumor cytosol estradiol-receptor complex has a Ka of 1.7 X 10(9) M-1 and 9.2 X 10(-10) M binding sites. Competition for the tritiated 17beta-estradiol binding sites in the renal tumor was similar to that in the uterus with respect to estrogenic compounds. Nonestrogenic steroids exhibited minimal competition at the same concentrations or higher. Substitution in the ring structure, particularly in position 3 of the phenolic A-ring, resulted in a considerable loss in the ability of such compounds to compete for these receptors. Aniestrogens were effective competitors for these estrogen receptors only at higher concentrations relative to the tritiated estradiol."} {"id": "PMID:175954", "title": "A quantitative study of the subcellular localization of 67Ga.", "content": "This paper describes a quantitative procedure for the isolation of 67 Ga-binding granules (GBG) from normal rat liver and Morris 5123C hepatoma homogenates by a combination of rate and isopyknic density gradient zonal centrifugation. Another class of GBG has been found that is much smaller than the lysosomal GBG we have previously described. These smaller particles, or microvesicles, bind the largest portion of the 67Ga found in the hepatoma whereas, in the liver, the GBG lysosomes are the major binding component. Previously, we had shown that considerably more 67Ga is taken up in hepatoma than in liver (as percentage of administered dose per g of tissue). The preferential association of 67Ga with these microvesicles in the 5123C hepatoma may be indicative of a basic difference between normal and malignant tissue.", "contents": "A quantitative study of the subcellular localization of 67Ga. This paper describes a quantitative procedure for the isolation of 67 Ga-binding granules (GBG) from normal rat liver and Morris 5123C hepatoma homogenates by a combination of rate and isopyknic density gradient zonal centrifugation. Another class of GBG has been found that is much smaller than the lysosomal GBG we have previously described. These smaller particles, or microvesicles, bind the largest portion of the 67Ga found in the hepatoma whereas, in the liver, the GBG lysosomes are the major binding component. Previously, we had shown that considerably more 67Ga is taken up in hepatoma than in liver (as percentage of administered dose per g of tissue). The preferential association of 67Ga with these microvesicles in the 5123C hepatoma may be indicative of a basic difference between normal and malignant tissue."} {"id": "PMID:175956", "title": "Some ultrastructural observations on the midgut epithelium of Isohypsibius augusti (Murray, 1907) (Eutardigrada).", "content": "The midgut epithelial cells of the eutardigrade Isophypsibius augusti are organized into a convoluted monolayer. Only a single cell type could be distinguished although this cell type displayed considerable morphological variation. The midgut begins with crescent-shaped cells. More distally the cells are of variable height depending on the stored amount of nutritional material. No regenerative cells are present. Adjoining cells are held together by apical zonulae continuae. All the cells are characterized by a striated border, some basal infoldings, cytosis vesicles, numerous mitochondria, and abundant rough endoplasmic reticulum. Dictyosomes occur in small numbers. Ovoid or spherical inclusions (spherites), often concentrically laminated, are common. The cells, especially those along the middle part of the gut, are filled with large amounts of nutritional storage which includes polysaccharide material. The possible functions of the midgut in Tardigrada are discussed.", "contents": "Some ultrastructural observations on the midgut epithelium of Isohypsibius augusti (Murray, 1907) (Eutardigrada). The midgut epithelial cells of the eutardigrade Isophypsibius augusti are organized into a convoluted monolayer. Only a single cell type could be distinguished although this cell type displayed considerable morphological variation. The midgut begins with crescent-shaped cells. More distally the cells are of variable height depending on the stored amount of nutritional material. No regenerative cells are present. Adjoining cells are held together by apical zonulae continuae. All the cells are characterized by a striated border, some basal infoldings, cytosis vesicles, numerous mitochondria, and abundant rough endoplasmic reticulum. Dictyosomes occur in small numbers. Ovoid or spherical inclusions (spherites), often concentrically laminated, are common. The cells, especially those along the middle part of the gut, are filled with large amounts of nutritional storage which includes polysaccharide material. The possible functions of the midgut in Tardigrada are discussed."} {"id": "PMID:175957", "title": "Immunohistochemical study on adenohypophysial primordia in organ culture.", "content": "Rathke's pouches isolated from rat fetuses on day 12 were maintained in organ culture for 9 days and investigated immunohistochemically to test whether or not the hypothalamus is involved in the cytodifferentiation of the adenohypophysis. The unlabeled antibody enzyme method demonstrated that the cultured tissue contains different types of glandular cells, i.e., adrenocorticotropin (ACTH)-, growth hormone (GH)-, luteinizing hormone (LH)-, thyrotropin (TSH)-, and prolactin-producing cells. Indirect evidence was also obtained to indicate the presence of melanocyte stimulating hormone (MSH)-cells. These findings suggest that adenohypophysial primordial cells of rats start to synthesize their respective hormones without stimuli from the neurosecretory substances of the brain which are known to be essential for the maintenance of the secretory activity of the adult gland.", "contents": "Immunohistochemical study on adenohypophysial primordia in organ culture. Rathke's pouches isolated from rat fetuses on day 12 were maintained in organ culture for 9 days and investigated immunohistochemically to test whether or not the hypothalamus is involved in the cytodifferentiation of the adenohypophysis. The unlabeled antibody enzyme method demonstrated that the cultured tissue contains different types of glandular cells, i.e., adrenocorticotropin (ACTH)-, growth hormone (GH)-, luteinizing hormone (LH)-, thyrotropin (TSH)-, and prolactin-producing cells. Indirect evidence was also obtained to indicate the presence of melanocyte stimulating hormone (MSH)-cells. These findings suggest that adenohypophysial primordial cells of rats start to synthesize their respective hormones without stimuli from the neurosecretory substances of the brain which are known to be essential for the maintenance of the secretory activity of the adult gland."} {"id": "PMID:175958", "title": "The fine structural localization of testicular phosphatases in man: the control testis.", "content": "Electron microscopic cytochemistry was used to determine the localization of five phosphatase enzymes-glucose-6-phosphatase, inosine diphosphatase, thiamine pyrophosphatase, acid phosphatase, and adenosine triphosphatase-in control human testes. Glucose-6-phosphatase occurred in the endoplasmic reticulum and nuclear envelope of Sertoli cells, Leydig cells and primitive spermatogonia, but was not observed in more advanced spermatogenic cells. The presence of glucose-6-phosphatase activity paralleled the presence of glycogen in spermatogenic cells, i.e., both occurred in type AL and AD spermatogonia but not in type AP or B spermatogonia or in more advanced spermatogenic cells. Inosine diphosphatase activity was found in the endoplasmic reticulum, nuclear envelope, and Golgi complex of Sertoli cells and all spermatogenic cells except late spermatids. Additionally, inosine diphosphatase activity was localized at the junctions between Sertoli cells and late spermatids, but was not associated with any other plasma membrane. Thiamine pyrophosphatase reaction product was found in the Golgi bodies of Sertoli cells and in spermatogenic cells through immature spermatids. Neither inosine diphosphatase nor thiamine pyrophosphatase was observed in the Golgi bodies of spermatids during acrosomal formation. Acid phosphatase activity was found in lysosomes of spermatogonia, spermatocytes, and spermatids, in lysosomes of Leydig cells, and in lysosomes, lipofuscin bodies, and Golgi cisternae of Sertoli cells. It is thought that Sertoli lysosomes play a role in the phagocytosis of degenerating germ cells; however, the role of spermatogenic or Leydig lysosomes is unknown. Adenosine triphosphatase activity occurred at the interfaces between two spermatogonia, and between Sertoli cells and spermatogonia, but was not observed in the spaces between two Sertoli cells, two spermatocytes, two spermatids, or between Sertoli cells and spermatocytes, or between Sertoli cells and spermatids.", "contents": "The fine structural localization of testicular phosphatases in man: the control testis. Electron microscopic cytochemistry was used to determine the localization of five phosphatase enzymes-glucose-6-phosphatase, inosine diphosphatase, thiamine pyrophosphatase, acid phosphatase, and adenosine triphosphatase-in control human testes. Glucose-6-phosphatase occurred in the endoplasmic reticulum and nuclear envelope of Sertoli cells, Leydig cells and primitive spermatogonia, but was not observed in more advanced spermatogenic cells. The presence of glucose-6-phosphatase activity paralleled the presence of glycogen in spermatogenic cells, i.e., both occurred in type AL and AD spermatogonia but not in type AP or B spermatogonia or in more advanced spermatogenic cells. Inosine diphosphatase activity was found in the endoplasmic reticulum, nuclear envelope, and Golgi complex of Sertoli cells and all spermatogenic cells except late spermatids. Additionally, inosine diphosphatase activity was localized at the junctions between Sertoli cells and late spermatids, but was not associated with any other plasma membrane. Thiamine pyrophosphatase reaction product was found in the Golgi bodies of Sertoli cells and in spermatogenic cells through immature spermatids. Neither inosine diphosphatase nor thiamine pyrophosphatase was observed in the Golgi bodies of spermatids during acrosomal formation. Acid phosphatase activity was found in lysosomes of spermatogonia, spermatocytes, and spermatids, in lysosomes of Leydig cells, and in lysosomes, lipofuscin bodies, and Golgi cisternae of Sertoli cells. It is thought that Sertoli lysosomes play a role in the phagocytosis of degenerating germ cells; however, the role of spermatogenic or Leydig lysosomes is unknown. Adenosine triphosphatase activity occurred at the interfaces between two spermatogonia, and between Sertoli cells and spermatogonia, but was not observed in the spaces between two Sertoli cells, two spermatocytes, two spermatids, or between Sertoli cells and spermatocytes, or between Sertoli cells and spermatids."} {"id": "PMID:175963", "title": "The formation and repair of single-strand breaks in DNA of cultured mammalian cells treated with UV-light, methylating agents or 4-nitroquinoline-1-oxide.", "content": "The technique of sedimentation in alkaline sucrose was used to examine the formation and repair of single-strand (SS) breaks in cultured mammalian cells that were treated with methyl methanesulfonate (MMS), methyl nitrosourea (MNUA), 4-nitroquinoline-1-oxide (4NQO) or UV-light. The SS breaks induced by MMS and 4NQO were largely repaired by HeLa cells during a 5-h post-treatment incubation. The SS breaks induced by MNUA and UV-light were not repaired by HeLa cells. L-cells were not able to repair the SS breaks induced by any of the agents, which correlates with the deficiency of these cells for repair synthesis of DNA. The following conclusions are discussed. MNUA and UV-light produce modifications in DNA which are not repaired but are translated into SS breaks in alkali. MMS produces SS breaks intracellularly but these are not derived from a simple depurination of methylated purines. 4NQO produces a modification in DNA which is translated into an SS break in alkali but which can be removed by an intracellular process.", "contents": "The formation and repair of single-strand breaks in DNA of cultured mammalian cells treated with UV-light, methylating agents or 4-nitroquinoline-1-oxide. The technique of sedimentation in alkaline sucrose was used to examine the formation and repair of single-strand (SS) breaks in cultured mammalian cells that were treated with methyl methanesulfonate (MMS), methyl nitrosourea (MNUA), 4-nitroquinoline-1-oxide (4NQO) or UV-light. The SS breaks induced by MMS and 4NQO were largely repaired by HeLa cells during a 5-h post-treatment incubation. The SS breaks induced by MNUA and UV-light were not repaired by HeLa cells. L-cells were not able to repair the SS breaks induced by any of the agents, which correlates with the deficiency of these cells for repair synthesis of DNA. The following conclusions are discussed. MNUA and UV-light produce modifications in DNA which are not repaired but are translated into SS breaks in alkali. MMS produces SS breaks intracellularly but these are not derived from a simple depurination of methylated purines. 4NQO produces a modification in DNA which is translated into an SS break in alkali but which can be removed by an intracellular process."} {"id": "PMID:175964", "title": "Alkylation of meseenger RNA by dimethylnitrosamine.", "content": "Rats were treated with radioactive dimethylnitrosamine or methyl methanesulphonate and the alkylation of various RNA fractions was determined 4 h later. It was found that after administration of dimethylnitrosamine, hepatic messenger RNA (isolated by binding to oligo(dT)-cellulose) and nuclear RNA were alkylated slightly, but significantly less than ribosomal RNA. After treatment with methyl methanesulphonate nuclear RNA was alkylated to a greater extent than either messenger or ribosomal RNA. The implications of these findings with respect to the mechanism by which dimethylnitrosamine inhibits liver protein synthesis are discussed.", "contents": "Alkylation of meseenger RNA by dimethylnitrosamine. Rats were treated with radioactive dimethylnitrosamine or methyl methanesulphonate and the alkylation of various RNA fractions was determined 4 h later. It was found that after administration of dimethylnitrosamine, hepatic messenger RNA (isolated by binding to oligo(dT)-cellulose) and nuclear RNA were alkylated slightly, but significantly less than ribosomal RNA. After treatment with methyl methanesulphonate nuclear RNA was alkylated to a greater extent than either messenger or ribosomal RNA. The implications of these findings with respect to the mechanism by which dimethylnitrosamine inhibits liver protein synthesis are discussed."} {"id": "PMID:175965", "title": "Mechanism of the autocatalytic formation of ferrihemoglobin by N,N-dimethylaniline-N-oxide. Structure and ferrihemoglobin forming activity of the purple dye.", "content": "The structure of the leuco compound of the purple dye which is formed in mixtrues of N,N-dimethylaniline-N-oxide (DANO) and ferrihemoglobin or ferricytochrome c was elucidated. IR, NMR, mass spectroscopy, and synthesis by oxidation of mixtures of N-methylaniline and 2-dimethylaminophenol showed that the leuco compound is produced by condensation of these two compounds. But only X-ray analysis proved the structure: 2-dimethylamino-4-(N-methylanilino)-phenol. The purple dye was produced from the leuco compound by withdrawal of two electrons and may be considered as resonance hybrid of the p-quinonimine and the o-quinonimine. When DANO was incubated with ferrihemoglobin or ferricytochrome c the oxygen of DANO was used for the production of the dye by oxidation of N-methylaniline and 2-dimethylaminophenol. The amount of N,N-dimethylaniline found in the incubation mixtures corresponded with the amount of purple dye produced. In the absence of molecular oxygen from incubation mixtures of DANO with cytochrome c the purple dye was formed at the same rate as under air. In blood in vitro the purple dye catalytically transferred electrons from ferrohemoglobin to molecuar oxygen. Its ferrihemoglobin-forming activity was lower than that of 4-dimethylaminophenol but higher than that of 2-dimethylaminophenol. The chemical mechanism of the autocatalytic formation of ferrihemoglobin by DANO is described.", "contents": "Mechanism of the autocatalytic formation of ferrihemoglobin by N,N-dimethylaniline-N-oxide. Structure and ferrihemoglobin forming activity of the purple dye. The structure of the leuco compound of the purple dye which is formed in mixtrues of N,N-dimethylaniline-N-oxide (DANO) and ferrihemoglobin or ferricytochrome c was elucidated. IR, NMR, mass spectroscopy, and synthesis by oxidation of mixtures of N-methylaniline and 2-dimethylaminophenol showed that the leuco compound is produced by condensation of these two compounds. But only X-ray analysis proved the structure: 2-dimethylamino-4-(N-methylanilino)-phenol. The purple dye was produced from the leuco compound by withdrawal of two electrons and may be considered as resonance hybrid of the p-quinonimine and the o-quinonimine. When DANO was incubated with ferrihemoglobin or ferricytochrome c the oxygen of DANO was used for the production of the dye by oxidation of N-methylaniline and 2-dimethylaminophenol. The amount of N,N-dimethylaniline found in the incubation mixtures corresponded with the amount of purple dye produced. In the absence of molecular oxygen from incubation mixtures of DANO with cytochrome c the purple dye was formed at the same rate as under air. In blood in vitro the purple dye catalytically transferred electrons from ferrohemoglobin to molecuar oxygen. Its ferrihemoglobin-forming activity was lower than that of 4-dimethylaminophenol but higher than that of 2-dimethylaminophenol. The chemical mechanism of the autocatalytic formation of ferrihemoglobin by DANO is described."} {"id": "PMID:175967", "title": "[Selection of cell lines resistant to cyclic AMP and theophylline from murine plasmocytoma MOPC 173. Cross resistance to ouabain and concanavalin A].", "content": "Using cAMP or theophyllin as selective agents, we obtained from contact inhibited and non contact inhibited cell lines, derived from the same plasmocytoma, different resistant cell lines. All of them were cAMP and theophyllin resistant and also ouabain and con A resistant as judged by the growth curves in presence of the different drugs.", "contents": "[Selection of cell lines resistant to cyclic AMP and theophylline from murine plasmocytoma MOPC 173. Cross resistance to ouabain and concanavalin A]. Using cAMP or theophyllin as selective agents, we obtained from contact inhibited and non contact inhibited cell lines, derived from the same plasmocytoma, different resistant cell lines. All of them were cAMP and theophyllin resistant and also ouabain and con A resistant as judged by the growth curves in presence of the different drugs."} {"id": "PMID:175968", "title": "[Estradiol and progesterone receptors in human endometrium during the menstrual cycle].", "content": "The concentrations of estradiol and progesterone receptors are measured in the cytoplasmic and nuclear fractions of endometrial samples obtained by biopsy throughout the menstrual cycle. The standardized micromethod accounts for the sites occupied by endogenous hormones and for interference by androgen receptors and plasma binding proteins. In normal women, the cellular concentration of estradiol receptor increases early in the cycle and decreases steadily after ovulation. The progesterone receptor is maximum between the 10th and 15th day of the cycle and decreases during the luteal phase. The nuclear/cytoplasmic ratios of both receptors follow the variations of circulating hormones. These data constitute a new basis for physiopathological and pharmacological investigations on the hormonal control of the human uterus.", "contents": "[Estradiol and progesterone receptors in human endometrium during the menstrual cycle]. The concentrations of estradiol and progesterone receptors are measured in the cytoplasmic and nuclear fractions of endometrial samples obtained by biopsy throughout the menstrual cycle. The standardized micromethod accounts for the sites occupied by endogenous hormones and for interference by androgen receptors and plasma binding proteins. In normal women, the cellular concentration of estradiol receptor increases early in the cycle and decreases steadily after ovulation. The progesterone receptor is maximum between the 10th and 15th day of the cycle and decreases during the luteal phase. The nuclear/cytoplasmic ratios of both receptors follow the variations of circulating hormones. These data constitute a new basis for physiopathological and pharmacological investigations on the hormonal control of the human uterus."} {"id": "PMID:175969", "title": "[Early stimulation of protein kinase activity during hormonal meiosis reinitiation in starfish ovocytes].", "content": "Total endogenous protein kinase activity has been compared in homogenates prepared from Marthasterias glacialis and Asterias rubens oocytes treated or not by 1-methyladenine, the hormone which triggers meiosis reinitiation. A 5 mn treatment at the threshold 10(-7) M concentration causes a significant increase (+ 20%) of these activities. This stimulation is maintained or even enhanced when homogenates are complemented with exogenous histones.", "contents": "[Early stimulation of protein kinase activity during hormonal meiosis reinitiation in starfish ovocytes]. Total endogenous protein kinase activity has been compared in homogenates prepared from Marthasterias glacialis and Asterias rubens oocytes treated or not by 1-methyladenine, the hormone which triggers meiosis reinitiation. A 5 mn treatment at the threshold 10(-7) M concentration causes a significant increase (+ 20%) of these activities. This stimulation is maintained or even enhanced when homogenates are complemented with exogenous histones."} {"id": "PMID:175970", "title": "[Short and long term depression of neuromuscular transmission in crayfish].", "content": "Following single excitation of the abdominal giant motoneuron of crayfish, an important depression of neuro-muscular transmission is observed for about 15 mn. The time course of recovery is not modified even after low frequency (1/30 Hz) repetitive stimulation. Recovery curves obtained for different Mg++ concentration in physiological solutions show two phases of depression: short-term depression which is largely reduced in high Mg++ concentrations - thus probably depending on transmitter depletion in motoneuron terminals - long-term depression which is not modified by changing Mg++ concentration and seems to be independent of depletion.", "contents": "[Short and long term depression of neuromuscular transmission in crayfish]. Following single excitation of the abdominal giant motoneuron of crayfish, an important depression of neuro-muscular transmission is observed for about 15 mn. The time course of recovery is not modified even after low frequency (1/30 Hz) repetitive stimulation. Recovery curves obtained for different Mg++ concentration in physiological solutions show two phases of depression: short-term depression which is largely reduced in high Mg++ concentrations - thus probably depending on transmitter depletion in motoneuron terminals - long-term depression which is not modified by changing Mg++ concentration and seems to be independent of depletion."} {"id": "PMID:175971", "title": "[Isolation of murine sarcoma virus not associated with XC plague forming leukemia virus].", "content": "The N-type MLg cells transformed by B-tropic MuSV (WN1802B) produced defective MuSV without detectable among of MuLV; the focus formation by the culture fluid required the co-infection of exogenous MuLV. After one passage of the virus in MLg cells, we obtained a virus preparation which was capable of inducing foci without the exogenous MuLV, but which remained negative in the XC test.", "contents": "[Isolation of murine sarcoma virus not associated with XC plague forming leukemia virus]. The N-type MLg cells transformed by B-tropic MuSV (WN1802B) produced defective MuSV without detectable among of MuLV; the focus formation by the culture fluid required the co-infection of exogenous MuLV. After one passage of the virus in MLg cells, we obtained a virus preparation which was capable of inducing foci without the exogenous MuLV, but which remained negative in the XC test."} {"id": "PMID:175972", "title": "Radionuclide methods in the evaluation of myocardial ischemia and infarction.", "content": "Radionuclide techniques that assess regional myocardial perfusion and detect acute myocardial infarction promise to provide critical information in the detection and evaluation of coronary artery disease and in the assessment of therapies aimed at limiting the degree of ischemia and the extent of tissue necrosis. Radioindicators such as 99mTc-tetracycline and 99mTc-pyrophosphate which are sequestered by acutely infarcted myocardium provide a direct method to detect an infarct and to determine its size. Regional alterations in myocardial perfusion can be assessed by myocardial scintigraphy performed after the injection of radiopotassium or one of its analogues with the patient either at rest or at exercise. A somewhat more accurate evaluation of the extent of altered perfusion can be obtained after the intracoronary injection of macro-aggregated particles. A quantitative index of altered perfusion can be obtained after the intracoronary injection of an inert gas such as 133Xe.", "contents": "Radionuclide methods in the evaluation of myocardial ischemia and infarction. Radionuclide techniques that assess regional myocardial perfusion and detect acute myocardial infarction promise to provide critical information in the detection and evaluation of coronary artery disease and in the assessment of therapies aimed at limiting the degree of ischemia and the extent of tissue necrosis. Radioindicators such as 99mTc-tetracycline and 99mTc-pyrophosphate which are sequestered by acutely infarcted myocardium provide a direct method to detect an infarct and to determine its size. Regional alterations in myocardial perfusion can be assessed by myocardial scintigraphy performed after the injection of radiopotassium or one of its analogues with the patient either at rest or at exercise. A somewhat more accurate evaluation of the extent of altered perfusion can be obtained after the intracoronary injection of macro-aggregated particles. A quantitative index of altered perfusion can be obtained after the intracoronary injection of an inert gas such as 133Xe."} {"id": "PMID:175976", "title": "Changes in electrophoretic mobilities of alpha-and beta-lipoproteins as a result of plasma delipidation.", "content": "A two-phase system containing the ternary mixture butanol/disopropyl ether/plasma in different proportions yields ordered delipidation of alpha-lipoproteins, pre-beta-lipoproteins- and beta-lipoproteins in plasma, as quantitated by densitometry after electrophoresis. As a consequence of delipidation the electrophoretic mobilities of pre-beta-lipoproteins and beta-lipoprotein increased, that of alpha-lipoprotein decreased.", "contents": "Changes in electrophoretic mobilities of alpha-and beta-lipoproteins as a result of plasma delipidation. A two-phase system containing the ternary mixture butanol/disopropyl ether/plasma in different proportions yields ordered delipidation of alpha-lipoproteins, pre-beta-lipoproteins- and beta-lipoproteins in plasma, as quantitated by densitometry after electrophoresis. As a consequence of delipidation the electrophoretic mobilities of pre-beta-lipoproteins and beta-lipoprotein increased, that of alpha-lipoprotein decreased."} {"id": "PMID:175977", "title": "Determination of apolipoprotein A and its constitutive A-I and A-II polypeptides by separate electroimmunoassays.", "content": "Electroimmunoassays (\"rocket\" electrophoresis) are described for human serum apolipoprotein A and its constitutive A-I and A-II polypeptides. Purified lipoprotein A, A-I, and A-II were used to prepare monospecific antisera and to standardize assays. These specific, rapid (5-8 h), precise (the within-and between-assay coefficients of variations are 5 and 7%, respectively), and accurate (by gravimetry) assays are applicable to measurement of these polypeptides in whole serum and in various density classes of lipoproteins. Comparable results are obtained with intact and delipidized lipoproteins. Results correlated well with those obtained by radial immunodiffusion or radioimmunoassay. However, the present procedure is more rapid than the former and simpler than the latter immunoassay. Concentrations of A-I and A-II in the serum of normal men and women were similar (143 +/- 24 and 146 +/- 78 mg/dl, respectively, for A-I and 78 +/- 17 and 83 +/- 25 mg/dl for A-II). Subjects with type lla, llb, and IV hyperlipoproteinemias had similar concentrations of both polypeptides, while patients with type I disease, lecithin:cholesterol acyltransferase deficiency and LP-A deficiency had lowest concentrations of A-I (0.3-30 mg/dl) and A-II (11-20 mg/dl). The molar ratio of A-I/A-II in the serum and high-density lipoproteins was close to unity.", "contents": "Determination of apolipoprotein A and its constitutive A-I and A-II polypeptides by separate electroimmunoassays. Electroimmunoassays (\"rocket\" electrophoresis) are described for human serum apolipoprotein A and its constitutive A-I and A-II polypeptides. Purified lipoprotein A, A-I, and A-II were used to prepare monospecific antisera and to standardize assays. These specific, rapid (5-8 h), precise (the within-and between-assay coefficients of variations are 5 and 7%, respectively), and accurate (by gravimetry) assays are applicable to measurement of these polypeptides in whole serum and in various density classes of lipoproteins. Comparable results are obtained with intact and delipidized lipoproteins. Results correlated well with those obtained by radial immunodiffusion or radioimmunoassay. However, the present procedure is more rapid than the former and simpler than the latter immunoassay. Concentrations of A-I and A-II in the serum of normal men and women were similar (143 +/- 24 and 146 +/- 78 mg/dl, respectively, for A-I and 78 +/- 17 and 83 +/- 25 mg/dl for A-II). Subjects with type lla, llb, and IV hyperlipoproteinemias had similar concentrations of both polypeptides, while patients with type I disease, lecithin:cholesterol acyltransferase deficiency and LP-A deficiency had lowest concentrations of A-I (0.3-30 mg/dl) and A-II (11-20 mg/dl). The molar ratio of A-I/A-II in the serum and high-density lipoproteins was close to unity."} {"id": "PMID:175978", "title": "Statistical characterization of the random errors in the radioimmunoassay dose--response variable.", "content": "We have developed practical methods for evaluating the magnitude of the random errors in radioimmunoassay dose--response variables, and the relationship between this error and position on the dose--response curve. This is important: to obtain appropriate weights for each point on the dose--response curve when utilizing least-squares curve-fitting methods; to evaluate whether the standards and the unknowns are subject to error of the same magnitude; for quality-control purposes; and to study the sources of errors in radioimmunoassay. Both standards and unknowns in radioimmunoassays for cAMP and cGMP were analyzed in triplicate. The same mean (Y), sample standard deviation, sy, and variance (2-y) of the response variable were calculated for each dose level. The relationship between s 2-y and y was calculated utilizing several models. Results for standards and unknowns from several assays were pooled, and a curve smoothing procedure was used to minimize random sampling errors. This pooling increased the reliability of the analysis, and confirmed the presence of the theoretically predicted nonuniformity of variance. Thus, the calculation of results from these radioimmunoassays should utilize a weighted least-squares curve-fitting program. These analyses have been computerized, and can be used as a \"pre-processor\" for programs for routine analysis of results of radioimmunoassay.", "contents": "Statistical characterization of the random errors in the radioimmunoassay dose--response variable. We have developed practical methods for evaluating the magnitude of the random errors in radioimmunoassay dose--response variables, and the relationship between this error and position on the dose--response curve. This is important: to obtain appropriate weights for each point on the dose--response curve when utilizing least-squares curve-fitting methods; to evaluate whether the standards and the unknowns are subject to error of the same magnitude; for quality-control purposes; and to study the sources of errors in radioimmunoassay. Both standards and unknowns in radioimmunoassays for cAMP and cGMP were analyzed in triplicate. The same mean (Y), sample standard deviation, sy, and variance (2-y) of the response variable were calculated for each dose level. The relationship between s 2-y and y was calculated utilizing several models. Results for standards and unknowns from several assays were pooled, and a curve smoothing procedure was used to minimize random sampling errors. This pooling increased the reliability of the analysis, and confirmed the presence of the theoretically predicted nonuniformity of variance. Thus, the calculation of results from these radioimmunoassays should utilize a weighted least-squares curve-fitting program. These analyses have been computerized, and can be used as a \"pre-processor\" for programs for routine analysis of results of radioimmunoassay."} {"id": "PMID:175979", "title": "Stability of fatty acids in hyperlipoproteinemic plasma during long-term storage.", "content": "Aliquots of hyperlipoproteinemic plasma were stored at -20 degrees C in a nitrogen atmosphere with added disodium ethylenediaminetetraacetate for up to one year, to determine the stability of fatty acids in the four major lipid classes under these conditions. Assays were performed at zero time and at 2, 5, and 12 months. No uniform fatty acid change was found. Minor statistically significant changes were found in total triglyceride fatty acids and in some of the individual fatty acids in cholesterol esters, phospholipid, and free fatty acids. These minor changes could not be accounted for by plasma lipid concentrations, lipolysis, or fatty acid peroxidation. Evidently, plasma can be stored in this manner for as long as a year without substantial change in fatty acids in any of the four major lipid classes.", "contents": "Stability of fatty acids in hyperlipoproteinemic plasma during long-term storage. Aliquots of hyperlipoproteinemic plasma were stored at -20 degrees C in a nitrogen atmosphere with added disodium ethylenediaminetetraacetate for up to one year, to determine the stability of fatty acids in the four major lipid classes under these conditions. Assays were performed at zero time and at 2, 5, and 12 months. No uniform fatty acid change was found. Minor statistically significant changes were found in total triglyceride fatty acids and in some of the individual fatty acids in cholesterol esters, phospholipid, and free fatty acids. These minor changes could not be accounted for by plasma lipid concentrations, lipolysis, or fatty acid peroxidation. Evidently, plasma can be stored in this manner for as long as a year without substantial change in fatty acids in any of the four major lipid classes."} {"id": "PMID:175980", "title": "Direct radioimmunoassay for serum estriol during pregnancy.", "content": "I describe an assay for serum estriol during pregnancy, which does not require prior extraction or chromatography of the serum. Fifty microliters of 20-fold diluted serum can be assayed to detect as little as 20 pg of estriol. For a 20 mug/liter serum estriol concentration the CV was 16%; for 100 mug/liter concentration it was 5%. There was no significant interference by serum \"binding\" proteins. The assay measures unconjugated estriol, estriol conjugated with either sulfate or glucuronide at the 3' position, and a portion of the estriol 16 alpha (beta-D-glucuronide). Serum estriol concentrations increase during gestation from a low at 20 weeks of less than 10 mug/liter to a high of 100-150 mug/liter at term. Serum estriol values correlate well with those for urinary total estrogens and with values for human placental lactogen in serum at various gestational ages.", "contents": "Direct radioimmunoassay for serum estriol during pregnancy. I describe an assay for serum estriol during pregnancy, which does not require prior extraction or chromatography of the serum. Fifty microliters of 20-fold diluted serum can be assayed to detect as little as 20 pg of estriol. For a 20 mug/liter serum estriol concentration the CV was 16%; for 100 mug/liter concentration it was 5%. There was no significant interference by serum \"binding\" proteins. The assay measures unconjugated estriol, estriol conjugated with either sulfate or glucuronide at the 3' position, and a portion of the estriol 16 alpha (beta-D-glucuronide). Serum estriol concentrations increase during gestation from a low at 20 weeks of less than 10 mug/liter to a high of 100-150 mug/liter at term. Serum estriol values correlate well with those for urinary total estrogens and with values for human placental lactogen in serum at various gestational ages."} {"id": "PMID:175981", "title": "Erythrocyte adenosine kinase activity in gout.", "content": "Erythrocyte adenosine kinase (AK) (EC 2.7.1.20) and guanosine monophosphate (GMP) reductase (EC 1.6.6.8) were measured in healthy male controls and primary gout subjects. Adenosine kinase activity in 19 controls and 26 gouty subjects was 0.717 +/- 0.176 and 0.615 +/- 0.128 nmol/mg protein/h, respectively. The difference was statistically significant (p less than 0.05). GMP reductase activity in 39 controls and 46 gouty subjects was 30.90 +/- 6.28 and 33.43 +/- 7.97 mumol/mg protein/h, respectively, without statistically significant difference.", "contents": "Erythrocyte adenosine kinase activity in gout. Erythrocyte adenosine kinase (AK) (EC 2.7.1.20) and guanosine monophosphate (GMP) reductase (EC 1.6.6.8) were measured in healthy male controls and primary gout subjects. Adenosine kinase activity in 19 controls and 26 gouty subjects was 0.717 +/- 0.176 and 0.615 +/- 0.128 nmol/mg protein/h, respectively. The difference was statistically significant (p less than 0.05). GMP reductase activity in 39 controls and 46 gouty subjects was 30.90 +/- 6.28 and 33.43 +/- 7.97 mumol/mg protein/h, respectively, without statistically significant difference."} {"id": "PMID:175982", "title": "Changes in the immunoelectrophoretic characteristics of serum alpha-I-lipoprotein induced by various dyes.", "content": "The effect of 8 dyes on the electrophoretic mobility of normal human serum alpha-1 lipoprotein has been examined. The two characteristics of increase in anodal mobility, and conformational changes of the immunoelectrophoretic precipitin arc suggesting polymorphism, were found to vary independently among the dyes tested. The results suggest that dye induced electrophoretic mobility alteration may represent a useful tool for examination of heterogeneity of alpha-1 lipoprotein.", "contents": "Changes in the immunoelectrophoretic characteristics of serum alpha-I-lipoprotein induced by various dyes. The effect of 8 dyes on the electrophoretic mobility of normal human serum alpha-1 lipoprotein has been examined. The two characteristics of increase in anodal mobility, and conformational changes of the immunoelectrophoretic precipitin arc suggesting polymorphism, were found to vary independently among the dyes tested. The results suggest that dye induced electrophoretic mobility alteration may represent a useful tool for examination of heterogeneity of alpha-1 lipoprotein."} {"id": "PMID:175987", "title": "Chemotherapy of herpesvirus infections.", "content": "Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented.", "contents": "Chemotherapy of herpesvirus infections. Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented."} {"id": "PMID:175988", "title": "Head pain.", "content": "Head pain can be a challenging, difficult, and interesting diagnostic problem. A detailed history and carefully performed and directed physical and laboratory examination will aid in the complex differential diagnosis--which includes structural disease of the eye, ear, nose, throat, teeth; trauma; central and peripheral nervous system infections and tumors; and various neuropathies of unknown cause. Systemic abnormalities such as hypertension are a frequent cause, as are emotional upset and tension. Other isolated and extremely rare causes, such as the anatomic abnormality of an elongated styloid process, cannot be discussed in a presentation of this length, but are included in the bibliography.", "contents": "Head pain. Head pain can be a challenging, difficult, and interesting diagnostic problem. A detailed history and carefully performed and directed physical and laboratory examination will aid in the complex differential diagnosis--which includes structural disease of the eye, ear, nose, throat, teeth; trauma; central and peripheral nervous system infections and tumors; and various neuropathies of unknown cause. Systemic abnormalities such as hypertension are a frequent cause, as are emotional upset and tension. Other isolated and extremely rare causes, such as the anatomic abnormality of an elongated styloid process, cannot be discussed in a presentation of this length, but are included in the bibliography."} {"id": "PMID:175984", "title": "Diffusion of bone morphogenetic activity from the residue of collagenase digested bone matrix gelatin through interstitial fluid.", "content": "Bone morphogenetic activity is transmitted from the residue of a collagenase digest of bone matrix gelatin not only across cellulose acetate membranes but also through an interstitial fluid filled duplex diffusion chamber (a distance 300 + 2,000 mum). Collagenolysis enhances dissociation of the bone morphogenetic property of bone matrix and dissemination among mesenchymal cells proliferating in the host bed surrounding the diffusion chamber. The bone morphogenetic response is associated with secretion of interstitial fluid, enzymes, and fibrin as well as formation of new collagen fibrils beaded with coarse ruthenium red granules in the pores of the cellulose acetate membrane. Membranes with pore sizes too small to accommodate either new collagen fibrils or mesenchymal cell microvilli do not transmit the morphogenetic response.", "contents": "Diffusion of bone morphogenetic activity from the residue of collagenase digested bone matrix gelatin through interstitial fluid. Bone morphogenetic activity is transmitted from the residue of a collagenase digest of bone matrix gelatin not only across cellulose acetate membranes but also through an interstitial fluid filled duplex diffusion chamber (a distance 300 + 2,000 mum). Collagenolysis enhances dissociation of the bone morphogenetic property of bone matrix and dissemination among mesenchymal cells proliferating in the host bed surrounding the diffusion chamber. The bone morphogenetic response is associated with secretion of interstitial fluid, enzymes, and fibrin as well as formation of new collagen fibrils beaded with coarse ruthenium red granules in the pores of the cellulose acetate membrane. Membranes with pore sizes too small to accommodate either new collagen fibrils or mesenchymal cell microvilli do not transmit the morphogenetic response."} {"id": "PMID:175985", "title": "Histological studies of subcutaneous and intraperitoneal implants of trypsin-prepared dermal collagen allografts in the rat.", "content": "The possibility of using allograft collagen for the permanent replacement of lost or damaged connective tissues has been examined in the rat. The cellular components of skin, which are known to be of major importance in allograft rejection, were removed by treating skin with a solution of crystalline trypsin at 15 degrees C. Non-collagenous structures were largely removed by 7 days, but the purification process continued up to 28 days without damage to the collagen fibrils. Dermal collagen allografts, which were implanted intraperitoneally or subcutaneously and biopsied 3-83 days after operation, became recellularized and revascularized without being being resorbed. In contrast to skin allografts, there was no evidence of cellular rejection of the collagen grafts, even when recipient animals had been sensitized to allogeneic skin from the same donor. Densensitization of collagen to collagenase, by treating dermal collagen with solutions of glutaraldehyde at concentrations ranging from 0.001-1.0 per cent, was also investigated in vitro and by implantation. The best results, in terms of preservation of the collagen bundle architecture and graft recellularization without persisting inflammation, were achieved with collaged pre-treated with a solution of 0.01% glutaraldehyde.", "contents": "Histological studies of subcutaneous and intraperitoneal implants of trypsin-prepared dermal collagen allografts in the rat. The possibility of using allograft collagen for the permanent replacement of lost or damaged connective tissues has been examined in the rat. The cellular components of skin, which are known to be of major importance in allograft rejection, were removed by treating skin with a solution of crystalline trypsin at 15 degrees C. Non-collagenous structures were largely removed by 7 days, but the purification process continued up to 28 days without damage to the collagen fibrils. Dermal collagen allografts, which were implanted intraperitoneally or subcutaneously and biopsied 3-83 days after operation, became recellularized and revascularized without being being resorbed. In contrast to skin allografts, there was no evidence of cellular rejection of the collagen grafts, even when recipient animals had been sensitized to allogeneic skin from the same donor. Densensitization of collagen to collagenase, by treating dermal collagen with solutions of glutaraldehyde at concentrations ranging from 0.001-1.0 per cent, was also investigated in vitro and by implantation. The best results, in terms of preservation of the collagen bundle architecture and graft recellularization without persisting inflammation, were achieved with collaged pre-treated with a solution of 0.01% glutaraldehyde."} {"id": "PMID:176003", "title": "Insoluble collagen I. The effect of substrate weight on the rate of solubilisation of polymeric collagen fibrils by bacterial collagenase.", "content": "The enzymic solubilisation of insoluble collagen fibrils by bacterial collagenase has been examined employing unlabelled polymeric collagen fibrils (PC), rhodamine labelled fibrils (RB-PC), and fluorescein labelled fibrils (F-PC) as substrates. The presence of the label did not affect the kinetics of enzyme digestion but enabled the solubilized products to be rapidly estimated. The quantity of substrate used was found to play a major role in determining the quantity of peptides solubilised by a given enzyme concentration. It is suggested that in the PC fibrils only a limited number of TC molecules were suitably located to form an enzyme substrate complex with bacterial collagenase. Conditions were found in which the F-PC and RB-PC could be used as substrates in the assay of this enzyme.", "contents": "Insoluble collagen I. The effect of substrate weight on the rate of solubilisation of polymeric collagen fibrils by bacterial collagenase. The enzymic solubilisation of insoluble collagen fibrils by bacterial collagenase has been examined employing unlabelled polymeric collagen fibrils (PC), rhodamine labelled fibrils (RB-PC), and fluorescein labelled fibrils (F-PC) as substrates. The presence of the label did not affect the kinetics of enzyme digestion but enabled the solubilized products to be rapidly estimated. The quantity of substrate used was found to play a major role in determining the quantity of peptides solubilised by a given enzyme concentration. It is suggested that in the PC fibrils only a limited number of TC molecules were suitably located to form an enzyme substrate complex with bacterial collagenase. Conditions were found in which the F-PC and RB-PC could be used as substrates in the assay of this enzyme."} {"id": "PMID:176004", "title": "Heparan sulfate of skin fibroblasts grown in culture.", "content": "Primary cultures of normal human skin fibroblasts were examined for glycosaminoglycan content. Heparan sulfate was found in the growth medium of these cells, in fractions obtained by sequential collagenase and trypsin treatments, and in the remaining intact cells. Heparan sulfate was found to be the major sulfated glycosaminoglycan of the trypsin fraction but appeared as a smaller proportion of the collagenase fraction. The heparan sulfate of the growth medium, the collagenase fraction, and the trypsin fraction appeared to be proteoglycan while intracellular material appeared to be mainly free polysaccharide. The collagenase fraction is thought to be representative of \"matrix\" material produced by the cells, while the trypsin fraction may represent external cell surface material. The trypsin fraction heparan sulfate polysaccharide was relatively homogeneous in size with an average molecular weight of approximately 40,000 relative to a chondroitin sulfate standard. It was also relatively homogeneous in sulfate content, containing an average of 0.8 sulfate groups per disaccharide repeating unit. Approximately 50% of this was N-sulfate.", "contents": "Heparan sulfate of skin fibroblasts grown in culture. Primary cultures of normal human skin fibroblasts were examined for glycosaminoglycan content. Heparan sulfate was found in the growth medium of these cells, in fractions obtained by sequential collagenase and trypsin treatments, and in the remaining intact cells. Heparan sulfate was found to be the major sulfated glycosaminoglycan of the trypsin fraction but appeared as a smaller proportion of the collagenase fraction. The heparan sulfate of the growth medium, the collagenase fraction, and the trypsin fraction appeared to be proteoglycan while intracellular material appeared to be mainly free polysaccharide. The collagenase fraction is thought to be representative of \"matrix\" material produced by the cells, while the trypsin fraction may represent external cell surface material. The trypsin fraction heparan sulfate polysaccharide was relatively homogeneous in size with an average molecular weight of approximately 40,000 relative to a chondroitin sulfate standard. It was also relatively homogeneous in sulfate content, containing an average of 0.8 sulfate groups per disaccharide repeating unit. Approximately 50% of this was N-sulfate."} {"id": "PMID:176005", "title": "Studies on hyaluronic acid. V. Relationship between the protein content and viscosity of rooster comb dermis hyaluronic acid.", "content": "Protein accounted for an average of 8.7% w/w of the hyaluronic acid obtained from rooster comb dermis extracts and three types of peptide constituents appeared to be present. A few collagen-like fibers were closely associated with the hyaluronic acid when samples were examined in the electron microscope and collagenase treatment decreased the intrinsic viscosity from 7000-5000 ml/g to 3900-2700 ml/g. The quantities of collagen present, however, were too small to detect chemically with the methods employed. The major peptide consituent was readily separated from the hyaluronic acid by fractionation in a cesium chloride gradient or by treatment with pronase. The viscosity was decreased by the density gradient procedure but not by the pronase digestion. Repeated fractionation in a cesium chloride gradient decreased the intrinsic viscosity still further and a small peptide constituent with a high glycine and serine content remained associated with a hyaluronic acid. The data suggest that an interaction or entanglement with collagen fibers is responsible for the high viscosity of hyaluronic acid in this tissue extract and that the viscosity of purified hyaluronic acid preparations is dependent upon interactions between adjacent polysaccharide chains. Interactions between the major peptide constituent and polysaccharide chains or the small residual peptide component remaining with hyaluronic acid after extensive purification procedures, however, appear to be involved in some organized structure because the presence of the major peptide constituent minimized the decrease in viscosity that occurred when hyaluronic acid samples were lyophilized.", "contents": "Studies on hyaluronic acid. V. Relationship between the protein content and viscosity of rooster comb dermis hyaluronic acid. Protein accounted for an average of 8.7% w/w of the hyaluronic acid obtained from rooster comb dermis extracts and three types of peptide constituents appeared to be present. A few collagen-like fibers were closely associated with the hyaluronic acid when samples were examined in the electron microscope and collagenase treatment decreased the intrinsic viscosity from 7000-5000 ml/g to 3900-2700 ml/g. The quantities of collagen present, however, were too small to detect chemically with the methods employed. The major peptide consituent was readily separated from the hyaluronic acid by fractionation in a cesium chloride gradient or by treatment with pronase. The viscosity was decreased by the density gradient procedure but not by the pronase digestion. Repeated fractionation in a cesium chloride gradient decreased the intrinsic viscosity still further and a small peptide constituent with a high glycine and serine content remained associated with a hyaluronic acid. The data suggest that an interaction or entanglement with collagen fibers is responsible for the high viscosity of hyaluronic acid in this tissue extract and that the viscosity of purified hyaluronic acid preparations is dependent upon interactions between adjacent polysaccharide chains. Interactions between the major peptide constituent and polysaccharide chains or the small residual peptide component remaining with hyaluronic acid after extensive purification procedures, however, appear to be involved in some organized structure because the presence of the major peptide constituent minimized the decrease in viscosity that occurred when hyaluronic acid samples were lyophilized."} {"id": "PMID:176006", "title": "Indoluble collagen II. The use of fluorescein labelled polymeric collagen fibrils in a very sensitive assay procedure for enzymes degrading insoluble collagen.", "content": "98% of the collagen in mature connective tissue is in the form of insoluble collagen fibers, consisting of bundles of polymeric collagen (PC) fibrils. The enzymes concerned in connective tissue remodeling degrade PC rather than tropocollagen (TC). TC is the most usual substrate for collagenase assays, and we believe it is essential to employ PC in any study of the activity of collagenolytic enzymes. In order to facilitate the study of enzymic degradation of PC we have labelled PC with fluorescein iso-thiocyanate to produce F-PC fibrils, containing 5 fluorescein labelled epilson-NH2 groups of lysine per TC molecule within the PC. The fluorescent F-PC is degraded at the same rate as PC with the release of hydroxyprolyl peptides but has the great advantage that the solubilised F-peptides can be quantitated by their fluorescent emission. The technique is described in detail employing bacterial collagenase and mammalian collagenase preparations to illustrate the methodology. The advantages of the fluorescent technique over the collagenolytic assay methods currently in use are outlined.", "contents": "Indoluble collagen II. The use of fluorescein labelled polymeric collagen fibrils in a very sensitive assay procedure for enzymes degrading insoluble collagen. 98% of the collagen in mature connective tissue is in the form of insoluble collagen fibers, consisting of bundles of polymeric collagen (PC) fibrils. The enzymes concerned in connective tissue remodeling degrade PC rather than tropocollagen (TC). TC is the most usual substrate for collagenase assays, and we believe it is essential to employ PC in any study of the activity of collagenolytic enzymes. In order to facilitate the study of enzymic degradation of PC we have labelled PC with fluorescein iso-thiocyanate to produce F-PC fibrils, containing 5 fluorescein labelled epilson-NH2 groups of lysine per TC molecule within the PC. The fluorescent F-PC is degraded at the same rate as PC with the release of hydroxyprolyl peptides but has the great advantage that the solubilised F-peptides can be quantitated by their fluorescent emission. The technique is described in detail employing bacterial collagenase and mammalian collagenase preparations to illustrate the methodology. The advantages of the fluorescent technique over the collagenolytic assay methods currently in use are outlined."} {"id": "PMID:176008", "title": "Mammary neoplasia in the guinea pig (Cavia porcellus).", "content": "Mammary tumors are reported in four guinea pigs and the literature is reviewed. It is concluded that mammary adenocarcinomas are second only to pulmonary adenomas as the most common epithelial tumors in the guinea pig. The sex incidence of mammary tumors is almost equal and both young and old animals are susceptible. Mammary tumors are generally locally invasive, rarely metastasize, are often quite large, and very vascular. Surgical excision of mammary tumors is possible but recurrence should be expected if the primary tumor is incompletely removed.", "contents": "Mammary neoplasia in the guinea pig (Cavia porcellus). Mammary tumors are reported in four guinea pigs and the literature is reviewed. It is concluded that mammary adenocarcinomas are second only to pulmonary adenomas as the most common epithelial tumors in the guinea pig. The sex incidence of mammary tumors is almost equal and both young and old animals are susceptible. Mammary tumors are generally locally invasive, rarely metastasize, are often quite large, and very vascular. Surgical excision of mammary tumors is possible but recurrence should be expected if the primary tumor is incompletely removed."} {"id": "PMID:176009", "title": "Current status and usefulness of operative cholangiography.", "content": "This article is a review of the recent literature on operative cholangiography. The objective is to summarize concisely the important contemporary viewpoints as an aid to students of radiology. To the practicing radiologist, it may offer a concise review of the subject and facilitate upgrading operative cholangiography in his hospital. The introduction covers statistical evidence of the growing dependence of biliary tract surgeons on operative cholangiography. The rudiments of diagnoses of the various diseases that can be detected by operative cholangiography are presented. Pertinent clinical facts along with cholangiographic diagrams are presented under arbitrary sections: I. Stones; II. Anomalies; III. Other Diseases; IV. Techniques of Operative Visualization of the Biliary System.", "contents": "Current status and usefulness of operative cholangiography. This article is a review of the recent literature on operative cholangiography. The objective is to summarize concisely the important contemporary viewpoints as an aid to students of radiology. To the practicing radiologist, it may offer a concise review of the subject and facilitate upgrading operative cholangiography in his hospital. The introduction covers statistical evidence of the growing dependence of biliary tract surgeons on operative cholangiography. The rudiments of diagnoses of the various diseases that can be detected by operative cholangiography are presented. Pertinent clinical facts along with cholangiographic diagrams are presented under arbitrary sections: I. Stones; II. Anomalies; III. Other Diseases; IV. Techniques of Operative Visualization of the Biliary System."} {"id": "PMID:176013", "title": "Ultrastructural surface alterations of serratia marcescens after exposure to polymyxin B and/or fresh human serum.", "content": "Exposure of Serratia marcescens cells to 10, 5, and 2.5 mug/ml of polymyxin B resulted in outer cell surface alterations that consisted of coarse, pleomorphic projections which revealed a double-contoured membrane structure. In contrast, fresh, but not heat-inactivated human serum caused the deposition of very fine, thread-like aggregates on the outer cell surface of exposed cells. The combination of polymyxin B and fresh human serum caused clearly discernible ultrastructural changes of the polymyxin and the fresh serum type, respectively.", "contents": "Ultrastructural surface alterations of serratia marcescens after exposure to polymyxin B and/or fresh human serum. Exposure of Serratia marcescens cells to 10, 5, and 2.5 mug/ml of polymyxin B resulted in outer cell surface alterations that consisted of coarse, pleomorphic projections which revealed a double-contoured membrane structure. In contrast, fresh, but not heat-inactivated human serum caused the deposition of very fine, thread-like aggregates on the outer cell surface of exposed cells. The combination of polymyxin B and fresh human serum caused clearly discernible ultrastructural changes of the polymyxin and the fresh serum type, respectively."} {"id": "PMID:176014", "title": "Antiviral 1,3,4-thiadiazoles. II. Effects on cellular and viral RNA synthesis in Mengo-virus-infected FL cells.", "content": "Three antiviral 1,3,4-thiadiazoles caused, when incubated together with 3H-uridine, a reduction of the incorporation rate into acid-insoluble material of FL cells. Using the method of prelabelling cellular RNA synthesis was not remarkably influenced. However, the substances tested act as specific inhibitors of the virus-induced RNA synthesis.", "contents": "Antiviral 1,3,4-thiadiazoles. II. Effects on cellular and viral RNA synthesis in Mengo-virus-infected FL cells. Three antiviral 1,3,4-thiadiazoles caused, when incubated together with 3H-uridine, a reduction of the incorporation rate into acid-insoluble material of FL cells. Using the method of prelabelling cellular RNA synthesis was not remarkably influenced. However, the substances tested act as specific inhibitors of the virus-induced RNA synthesis."} {"id": "PMID:176016", "title": "Pneumatosis cystoides intestinalis.", "content": "Pneumatosis cystoides intestinalis (PCI) is an uncommon disease of previously unknown etiology, characterized by the presence of gas-filled cysts in the walls of some portion of the gastrointestinal tract. This investigation showed that PCI was readily produced in the germfree rat by inoculating its peritoneal cavity with a pure culture of either C. perfringens or C. tertium. Similar inoculation of the germfree animal with any one of eight other clostridia species did not result in the formation of PCI. The bacterial theory for the formation of at least some cases of PCI is now established. This work suggests that part of the treatment of those fulminating diseases known to be frequently associated with PCI should be directed at controlling a possible clostridial infection.", "contents": "Pneumatosis cystoides intestinalis. Pneumatosis cystoides intestinalis (PCI) is an uncommon disease of previously unknown etiology, characterized by the presence of gas-filled cysts in the walls of some portion of the gastrointestinal tract. This investigation showed that PCI was readily produced in the germfree rat by inoculating its peritoneal cavity with a pure culture of either C. perfringens or C. tertium. Similar inoculation of the germfree animal with any one of eight other clostridia species did not result in the formation of PCI. The bacterial theory for the formation of at least some cases of PCI is now established. This work suggests that part of the treatment of those fulminating diseases known to be frequently associated with PCI should be directed at controlling a possible clostridial infection."} {"id": "PMID:176017", "title": "Anal infections caused by herpes simplex virus.", "content": "Herpes simplex infections of the perianal skin and anal canal are not uncommon, as evidenced by the present series of 16 cases, but have rarely been reported in the literature of the past. They are caused by the HSV-2 virus, which is also associated with genital lesions. There is abundant evidence that anogenital herpes is a venereal disease. Anal herpes is most commonly transmitted by anal intercourse. When the infection is present inside the anal canal, especially in a primary attack, the pain can be quite dibilitating. The diagnosis can usually be made on clinical grounds by recognizing the typical vesicles or aphthous ulcers, together with inguinal lymphadenopathy. The disease is self-limiting, but may be recurrent. Asymptomatic homosexuals may represent a large reservoir of the disease, which appears to be on the increase in our society. Cytology, immunofluorescence, viral cultures and serologic tests can be used for laboratory confirmation of the diagnosis. Newer methods of treatment with vaccine containing heat-inactivated virus, and use of photoinactivation following topical application of heterotricyclic dyes, show promise.", "contents": "Anal infections caused by herpes simplex virus. Herpes simplex infections of the perianal skin and anal canal are not uncommon, as evidenced by the present series of 16 cases, but have rarely been reported in the literature of the past. They are caused by the HSV-2 virus, which is also associated with genital lesions. There is abundant evidence that anogenital herpes is a venereal disease. Anal herpes is most commonly transmitted by anal intercourse. When the infection is present inside the anal canal, especially in a primary attack, the pain can be quite dibilitating. The diagnosis can usually be made on clinical grounds by recognizing the typical vesicles or aphthous ulcers, together with inguinal lymphadenopathy. The disease is self-limiting, but may be recurrent. Asymptomatic homosexuals may represent a large reservoir of the disease, which appears to be on the increase in our society. Cytology, immunofluorescence, viral cultures and serologic tests can be used for laboratory confirmation of the diagnosis. Newer methods of treatment with vaccine containing heat-inactivated virus, and use of photoinactivation following topical application of heterotricyclic dyes, show promise."} {"id": "PMID:176021", "title": "[Congenital cytomegalovirus infection after maternal renal transplantation (author's transl)].", "content": "A 34-year-old female gave birth to a 32 to 35 week-old girl one year after she had undergone renal transplantation. The child was dwarfed and microcephalic and also had congenital platelet deficiency and purpura. In addition it was anaemic and suffered from severe neonatal icterus. An initial hypogammaglobulinaemia disappeared except for low IgA levels. The immunoglobulin deficiency is probably correlated with the virologically and serologically proven cytomegalovirus infection. The incidence of this disease seems to be high in children of mothers with renal transplantations.", "contents": "[Congenital cytomegalovirus infection after maternal renal transplantation (author's transl)]. A 34-year-old female gave birth to a 32 to 35 week-old girl one year after she had undergone renal transplantation. The child was dwarfed and microcephalic and also had congenital platelet deficiency and purpura. In addition it was anaemic and suffered from severe neonatal icterus. An initial hypogammaglobulinaemia disappeared except for low IgA levels. The immunoglobulin deficiency is probably correlated with the virologically and serologically proven cytomegalovirus infection. The incidence of this disease seems to be high in children of mothers with renal transplantations."} {"id": "PMID:176027", "title": "Phase transitions in the membrane of a marine bacterium, Pseudomonas BAL-31.", "content": "An unsaturated fatty acid auxotroph, strain UFA, isolated from the marine pseudomonad Pseudomonas BAL-31, host cell of the lipid-containing bacteriophage PM2, was grown in media supplemented with different unsaturated fatty acids. Under these conditions the fatty acid composition of the cell could be altered drastically. The phase transition in the native membrane and in the extracted lipids was analyzed by electron spin resonance using a nitroxide spin probe. Membranes prepared from strain UFA grown in cis16:1 or trans16:1 showed one transition at 9.4 degrees C and 12.4 degrees C respectively. Extracted lipids in both cases had almost the same transition temperature as that of the intact membrane. Membranes prepared from Pseudomonas BAL-31 had one transition at approximately 12 degrees C, on the other hand there was no clear cut phase transition using extracted lipids. Replication of bacteriophage PM2 took place below the transition temperature of the membrane lipids in the case where strain UFA was grown in tran16:1. Other cases were not studied.", "contents": "Phase transitions in the membrane of a marine bacterium, Pseudomonas BAL-31. An unsaturated fatty acid auxotroph, strain UFA, isolated from the marine pseudomonad Pseudomonas BAL-31, host cell of the lipid-containing bacteriophage PM2, was grown in media supplemented with different unsaturated fatty acids. Under these conditions the fatty acid composition of the cell could be altered drastically. The phase transition in the native membrane and in the extracted lipids was analyzed by electron spin resonance using a nitroxide spin probe. Membranes prepared from strain UFA grown in cis16:1 or trans16:1 showed one transition at 9.4 degrees C and 12.4 degrees C respectively. Extracted lipids in both cases had almost the same transition temperature as that of the intact membrane. Membranes prepared from Pseudomonas BAL-31 had one transition at approximately 12 degrees C, on the other hand there was no clear cut phase transition using extracted lipids. Replication of bacteriophage PM2 took place below the transition temperature of the membrane lipids in the case where strain UFA was grown in tran16:1. Other cases were not studied."} {"id": "PMID:176028", "title": "Norepinephrine-induced shift in levels of adenosine 3':5'-monophosphate and ATP parallel to increased respiratory rate and lipolysis in isolated hamster brown-fat cells.", "content": "1. Isolated brown fat cells from hamster respond to added catecholamines with a temporary increase in respiratory rate and an extended lipolysis. 2. From experiments with catecholamines and alpha and beta-blockers, the receptors of these cells are classified as beta according to classical definition. 3. Norepinephrine induces a rapid increase in adenosine 3':5'-monophosphate levels which parallels in time the stimulated respiration. Maximal adenosine 3':5'-monophosphate levels are reached within 1-3 min and are followed by a continuous decline. 4. Parallel to the catecholamine-induced respiration and lipolysis there is a pronounced drop in ATP levels. This energy depletion could be reversed by addition within 5 min after norepinephrine of the beta-blocker propranolol. 5. The nucleotide pattern in isolated hamster brown fat cells after norepinephrine addition was mimicked in experiments with isolated hamster brown fat mitochondria. From these experiments it is concluded that a high ratio of AMP and ADP over ATP decreases the respiratory rate when endogenous free fatty acids are oxidized.", "contents": "Norepinephrine-induced shift in levels of adenosine 3':5'-monophosphate and ATP parallel to increased respiratory rate and lipolysis in isolated hamster brown-fat cells. 1. Isolated brown fat cells from hamster respond to added catecholamines with a temporary increase in respiratory rate and an extended lipolysis. 2. From experiments with catecholamines and alpha and beta-blockers, the receptors of these cells are classified as beta according to classical definition. 3. Norepinephrine induces a rapid increase in adenosine 3':5'-monophosphate levels which parallels in time the stimulated respiration. Maximal adenosine 3':5'-monophosphate levels are reached within 1-3 min and are followed by a continuous decline. 4. Parallel to the catecholamine-induced respiration and lipolysis there is a pronounced drop in ATP levels. This energy depletion could be reversed by addition within 5 min after norepinephrine of the beta-blocker propranolol. 5. The nucleotide pattern in isolated hamster brown fat cells after norepinephrine addition was mimicked in experiments with isolated hamster brown fat mitochondria. From these experiments it is concluded that a high ratio of AMP and ADP over ATP decreases the respiratory rate when endogenous free fatty acids are oxidized."} {"id": "PMID:176032", "title": "Modifications in the release of rat growth hormone in vitro and the morphology of rat anterior pituitaries incubated in various ionophores.", "content": "The ionophore A23187 increased the release of rat growth hormone in the presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; a second ionophore X537A inhibited growth hormone release induced by the methylxanthine. A23187 did not alter rat growth hormone release in the absence of 3-isobutyl-1-methylxanthine, but X537A enhanced hormone release in the absence of calcium or in the presence or somatostatin. These findings provide further evidence that both calcium and cyclic AMP are important in the regulation of growth hormone release. Tissue incubated in X537A combined electronlucent vesicles apparently derived from the Golgi apparatus, swollen granules and mitochondria with dense matrices. Tissue incubated in the presence of valinomycin or A23187 did not show altered morphology of either secretory granules or the Golgi complex. Possible mechanisms of these changes are discussed.", "contents": "Modifications in the release of rat growth hormone in vitro and the morphology of rat anterior pituitaries incubated in various ionophores. The ionophore A23187 increased the release of rat growth hormone in the presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; a second ionophore X537A inhibited growth hormone release induced by the methylxanthine. A23187 did not alter rat growth hormone release in the absence of 3-isobutyl-1-methylxanthine, but X537A enhanced hormone release in the absence of calcium or in the presence or somatostatin. These findings provide further evidence that both calcium and cyclic AMP are important in the regulation of growth hormone release. Tissue incubated in X537A combined electronlucent vesicles apparently derived from the Golgi apparatus, swollen granules and mitochondria with dense matrices. Tissue incubated in the presence of valinomycin or A23187 did not show altered morphology of either secretory granules or the Golgi complex. Possible mechanisms of these changes are discussed."} {"id": "PMID:176033", "title": "Human adipose tissue in culture. IV. Evidence for the formation of a hormone antagonist by catecholamines.", "content": "Explants of human adipose tissue were cultured for several days with noradrenaline (NA). After the culture period the explants were carefully washed, preincubated and then incubated for 2 h by a technique analogous to those generally used to study adipose tissue metabolism. The results show that explants cultured with NA were considerably less responsive to the acute lipolytic effect of catecholamines than explants not previously exposed to NA. The diminished responsiveness could not be reversed by the addition of phentolamine or by preincubating the explants with a prostaglandin antagonist and it was dependent upon the concentration of noradrenaline used in the culture medium as well as upon the period of time that the explants were exposed to the hormone. The cyclic AMP (cAMP) levels did not increase in response to NA in these explants. Addition of theophylline or dibutyryl cAMP elicited a lipolytic response. However, the phosphodiesterase levels were not increased in the explants cultured with noradrenaline. When freshly excised tissue specimens were incubated in the culture medium which had previously contained NA the acute lipolytic effect of catecholamines was blunted. The results indicate that an antagonist is formed during the incubation with NA which inhibits the responsiveness to catecholamines. The effect of the antagonist seems to be exerted at a step prior to the formation of cAMP.", "contents": "Human adipose tissue in culture. IV. Evidence for the formation of a hormone antagonist by catecholamines. Explants of human adipose tissue were cultured for several days with noradrenaline (NA). After the culture period the explants were carefully washed, preincubated and then incubated for 2 h by a technique analogous to those generally used to study adipose tissue metabolism. The results show that explants cultured with NA were considerably less responsive to the acute lipolytic effect of catecholamines than explants not previously exposed to NA. The diminished responsiveness could not be reversed by the addition of phentolamine or by preincubating the explants with a prostaglandin antagonist and it was dependent upon the concentration of noradrenaline used in the culture medium as well as upon the period of time that the explants were exposed to the hormone. The cyclic AMP (cAMP) levels did not increase in response to NA in these explants. Addition of theophylline or dibutyryl cAMP elicited a lipolytic response. However, the phosphodiesterase levels were not increased in the explants cultured with noradrenaline. When freshly excised tissue specimens were incubated in the culture medium which had previously contained NA the acute lipolytic effect of catecholamines was blunted. The results indicate that an antagonist is formed during the incubation with NA which inhibits the responsiveness to catecholamines. The effect of the antagonist seems to be exerted at a step prior to the formation of cAMP."} {"id": "PMID:176034", "title": "Effect on plasma aldosterone, renin activity and cortisol of acute volume depletion induced by ethacrynic acid under constant infusion of angiotensin II and dexamethasone in man.", "content": "The influence on plasma aldosterone of acute volume depletion induced by ethacrynic acid was studied in man. The experiments were performed during the morning in supine healthy males receiving a control infusion of 5% glucose or an infusion of angiotensin II (AII) to suppress endogenous renin production or an infusion of dexamethasone to suppress endogenous ACTH. Ethacrynic acid induced in all circumstances a similar diuresis and volume depletion. The rise of plasma renin activity (PRA) was effectively suppressed by AII and the rise of plasma cortisol by dexamethasone. Plasma aldosterone (PA) rose markedly even when the elevation of PRA or cortisol were suppressed. Yet when both endogenous renin and ACTH secretion were blocked, PA rose much less after ethacrynic acid. This residual increase could be attributed mainly to a decrease of the metabolic clearance rate (MCR) of aldosterone which had been measured before and after ethacrynic acid administration. The data presented indicate that multiple factors influencing PA after acute volume depletion could be dissected out and that renin, ACTH and a decrease of the MCR each contribute to the elevation of PA.", "contents": "Effect on plasma aldosterone, renin activity and cortisol of acute volume depletion induced by ethacrynic acid under constant infusion of angiotensin II and dexamethasone in man. The influence on plasma aldosterone of acute volume depletion induced by ethacrynic acid was studied in man. The experiments were performed during the morning in supine healthy males receiving a control infusion of 5% glucose or an infusion of angiotensin II (AII) to suppress endogenous renin production or an infusion of dexamethasone to suppress endogenous ACTH. Ethacrynic acid induced in all circumstances a similar diuresis and volume depletion. The rise of plasma renin activity (PRA) was effectively suppressed by AII and the rise of plasma cortisol by dexamethasone. Plasma aldosterone (PA) rose markedly even when the elevation of PRA or cortisol were suppressed. Yet when both endogenous renin and ACTH secretion were blocked, PA rose much less after ethacrynic acid. This residual increase could be attributed mainly to a decrease of the metabolic clearance rate (MCR) of aldosterone which had been measured before and after ethacrynic acid administration. The data presented indicate that multiple factors influencing PA after acute volume depletion could be dissected out and that renin, ACTH and a decrease of the MCR each contribute to the elevation of PA."} {"id": "PMID:176035", "title": "The pharmacological actions of some polymethylene-bis-(hydroxyethyl)-dimethyl-ammonium compounds on cholinergic transmission.", "content": "Some polymethylene-bis-(hydroxyethyl)-dimethyl-ammonium (dicholine) compounds containing from 7 to 10 methylene groups between the quaternary nitrogen atoms, have been studied for activity at various sites of cholinergic transmission. The post-junctional activity of the compounds was investigated on the frog rectus abdominis muscle. Small doses of C8-, C9-, and C10-dicholine potentiated ACh contractions, however larger doses of all the dicholine compounds blocked the nicotinic receptor sites of the frog rectus muscle. The dicholine compounds blocked neuromuscular transmission in the rat phrenic nerve diaphragm. These actions at the rat neuromuscular junction are compared with the purely post-junctional actions on the frog rectus muscle. Although the compounds exert anticholinesterase activity in vitro it is suggested that this effect plays little part in the action of the drugs at the neuromuscular junction. It is concluded that the dicholine compounds have both pre- and post-junctional activity at the neuromuscular junction. The dicholine compounds are acetylated at varying rates by partially purified choline acetyltransferase (ChAc) although all are acetylated less readily than choline. The rate of acetylation of the dicholine compounds by ChAc parallels their activity in blocking neuromuscular transmission and it is suggested that other quaternary ammonium compounds containing hydroxyl or hydroxyethyl groupings may be acetylated by ChAc and this may affect their blocking action at the neuromuscular junction.", "contents": "The pharmacological actions of some polymethylene-bis-(hydroxyethyl)-dimethyl-ammonium compounds on cholinergic transmission. Some polymethylene-bis-(hydroxyethyl)-dimethyl-ammonium (dicholine) compounds containing from 7 to 10 methylene groups between the quaternary nitrogen atoms, have been studied for activity at various sites of cholinergic transmission. The post-junctional activity of the compounds was investigated on the frog rectus abdominis muscle. Small doses of C8-, C9-, and C10-dicholine potentiated ACh contractions, however larger doses of all the dicholine compounds blocked the nicotinic receptor sites of the frog rectus muscle. The dicholine compounds blocked neuromuscular transmission in the rat phrenic nerve diaphragm. These actions at the rat neuromuscular junction are compared with the purely post-junctional actions on the frog rectus muscle. Although the compounds exert anticholinesterase activity in vitro it is suggested that this effect plays little part in the action of the drugs at the neuromuscular junction. It is concluded that the dicholine compounds have both pre- and post-junctional activity at the neuromuscular junction. The dicholine compounds are acetylated at varying rates by partially purified choline acetyltransferase (ChAc) although all are acetylated less readily than choline. The rate of acetylation of the dicholine compounds by ChAc parallels their activity in blocking neuromuscular transmission and it is suggested that other quaternary ammonium compounds containing hydroxyl or hydroxyethyl groupings may be acetylated by ChAc and this may affect their blocking action at the neuromuscular junction."} {"id": "PMID:176036", "title": "Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation.", "content": "Methylxanthines (10(-5) to 10(-3)M) were found to increase the amplitude of contractions of guinea-pig ileum induced by transmural stimulation but to inhibit those induced by acetylcholine or histamine. The order of the abilities of methylxanthines to augment the contractile responses was theobromine greater than caffeine greater than theophylline. When the contractions were completely suppressed by reduction of the calcium content in the medium or by addition of cyclic AMP, methylxanthines restored the responses effectively, just as does addition of calcium. Methylxanthines also accelerated the release of acetylcholine from the ileum associated with stimulation. Imidazole (3 X 10(-5) to 10(-3) M) had an essentially similar effect to methylxanthines in potentiating the contractile responses and in augmenting the release of acetylcholine. The present results indicate that the potentiating effects of methylxanthines and imidazole are due to an action on the nerve terminals, not on the postsynaptic membranes or contractile elements. Therefore, it si concluded that theit potentiating actions are due to facilitation of the movement of calcium in the nerve terminals on excitation, resulting in increased release of acetylcholine, and are not due to the effect of cyclic AMP formed as a result of their inhibitory actions on phosphodiesterase.", "contents": "Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation. Methylxanthines (10(-5) to 10(-3)M) were found to increase the amplitude of contractions of guinea-pig ileum induced by transmural stimulation but to inhibit those induced by acetylcholine or histamine. The order of the abilities of methylxanthines to augment the contractile responses was theobromine greater than caffeine greater than theophylline. When the contractions were completely suppressed by reduction of the calcium content in the medium or by addition of cyclic AMP, methylxanthines restored the responses effectively, just as does addition of calcium. Methylxanthines also accelerated the release of acetylcholine from the ileum associated with stimulation. Imidazole (3 X 10(-5) to 10(-3) M) had an essentially similar effect to methylxanthines in potentiating the contractile responses and in augmenting the release of acetylcholine. The present results indicate that the potentiating effects of methylxanthines and imidazole are due to an action on the nerve terminals, not on the postsynaptic membranes or contractile elements. Therefore, it si concluded that theit potentiating actions are due to facilitation of the movement of calcium in the nerve terminals on excitation, resulting in increased release of acetylcholine, and are not due to the effect of cyclic AMP formed as a result of their inhibitory actions on phosphodiesterase."} {"id": "PMID:176037", "title": "[Toxicologic and pharmacologic study of tributyltin oxide (TBTO)].", "content": "Toxicological study on bis-(tributyl-tin) oxyde shows a delayed toxicity of this compound in acute experiments. The same result is obtained in sub-chronic study. Most of the animals die after a great loss of weight. In pharmacological study, T. B. T. O. depresses central nervous system, but his action on ortho and parasympathetic system is slight and non specific. In rat, rabbit and dog, the effect is a fall in blood pressure that result from a depression of the vascular smooth muscle. The death of the animal is due to respiratory arrest by a central mechanism.", "contents": "[Toxicologic and pharmacologic study of tributyltin oxide (TBTO)]. Toxicological study on bis-(tributyl-tin) oxyde shows a delayed toxicity of this compound in acute experiments. The same result is obtained in sub-chronic study. Most of the animals die after a great loss of weight. In pharmacological study, T. B. T. O. depresses central nervous system, but his action on ortho and parasympathetic system is slight and non specific. In rat, rabbit and dog, the effect is a fall in blood pressure that result from a depression of the vascular smooth muscle. The death of the animal is due to respiratory arrest by a central mechanism."} {"id": "PMID:176038", "title": "[The irritant and allergenic action of two isocyanates: toluene diisocyanate (TDI) and diphenylmethane diisocyanate (MDI)].", "content": "This is a study on the irritant capacity of two isocyanates (T. D. I. Toluene diisocyanate and M. D. I. diphenyl methane diisocyanate). The experiment was carried out on the hide and ocular mucous membrane of albino rabbits, using Draize method as well as the method for appraising cosmetics. An histopathological examination of the evolution of the lesions was then achieved together with a study on the delayed allergenic capacity. This study was carried out on albino guinea-pig hides using Kligman and Magnusson technique. In these experimental conditions, the conclusions were the following:--on rabbit hide, T. D. I. is a medium irritant, more caustic than M. D. I.,--on ocular mucous membrane, M. D. I. is a mild irritant; T. D. I. a strong one,--on guinea-pig hide, T. D. I. and M. D. I. may induce cutaneous sensitivity similar to contact allergy. Their allergenic capacity is long lasting but varies according to the allergen concentration.", "contents": "[The irritant and allergenic action of two isocyanates: toluene diisocyanate (TDI) and diphenylmethane diisocyanate (MDI)]. This is a study on the irritant capacity of two isocyanates (T. D. I. Toluene diisocyanate and M. D. I. diphenyl methane diisocyanate). The experiment was carried out on the hide and ocular mucous membrane of albino rabbits, using Draize method as well as the method for appraising cosmetics. An histopathological examination of the evolution of the lesions was then achieved together with a study on the delayed allergenic capacity. This study was carried out on albino guinea-pig hides using Kligman and Magnusson technique. In these experimental conditions, the conclusions were the following:--on rabbit hide, T. D. I. is a medium irritant, more caustic than M. D. I.,--on ocular mucous membrane, M. D. I. is a mild irritant; T. D. I. a strong one,--on guinea-pig hide, T. D. I. and M. D. I. may induce cutaneous sensitivity similar to contact allergy. Their allergenic capacity is long lasting but varies according to the allergen concentration."} {"id": "PMID:176039", "title": "[Binding of delta-8-THC to human serum proteins: binding as a function of lipoprotein composition].", "content": "In accordance with the function of the human lipoprotein composition, using serum of different lipid profiles, the distribution of delta8tetrahydrocannabinol, as isomer of delta9THC, was studied through the use of ultracentrifugation and fraction isolation, followed by biochemical analysis of the VLDL, LDL, and HDL fractions, as well as that of the non-lipoprotein protein fraction. The results indicate the existence of a linear correlation between the distribution of delta8THC and the phospholipids of the lipoprotein cenapse. No correlation between the quantity of bound delta8THC and the other lipoprotein constituents cholesterol, triglycerides, total lipids or protein could be observed.", "contents": "[Binding of delta-8-THC to human serum proteins: binding as a function of lipoprotein composition]. In accordance with the function of the human lipoprotein composition, using serum of different lipid profiles, the distribution of delta8tetrahydrocannabinol, as isomer of delta9THC, was studied through the use of ultracentrifugation and fraction isolation, followed by biochemical analysis of the VLDL, LDL, and HDL fractions, as well as that of the non-lipoprotein protein fraction. The results indicate the existence of a linear correlation between the distribution of delta8THC and the phospholipids of the lipoprotein cenapse. No correlation between the quantity of bound delta8THC and the other lipoprotein constituents cholesterol, triglycerides, total lipids or protein could be observed."} {"id": "PMID:176045", "title": "Electrophysiological properties of nucleus reticularis tegmenti pontis cells: antidromic and synaptic activation.", "content": "Antidromically and synaptically activated spike and synaptic potentials in the nucleus reticularis tegmenti pontis (NRTP) of the cat were recorded intracellularly. The antidromic firing of the NRTP neurone is composed of IS-SD spikes with short duration and short spike-after-hyperpolarization. Membrane resistance and firing patterns were studied by applying depolarizing and hyperpolarizing current through the recording electrode. Findings indicate that the NRTP neurone has a relatively high membrane resistance and is capable of firing at a high frequency. Single shock stimulation of the interpositus (IP) and lateral nucleus (LN) of the cerebellum, brachium conjunctivum (BC), red nucleus (RN) and cerebral peduncle (CP) induced monosynaptic EPSPs in the NRTP neurones. Superior vestibular nucleus (SVN) stimulation induced monosynaptic IPSPs. Collision tests showed that (1) NRTP neurones are activated by the axons of IP and LN neurones which travel through BC, (2) these axons also send collaterals to RN, and (3) there is convergence of cerebellar, cerebral and brain stem inputs to a single NRTP neurone.", "contents": "Electrophysiological properties of nucleus reticularis tegmenti pontis cells: antidromic and synaptic activation. Antidromically and synaptically activated spike and synaptic potentials in the nucleus reticularis tegmenti pontis (NRTP) of the cat were recorded intracellularly. The antidromic firing of the NRTP neurone is composed of IS-SD spikes with short duration and short spike-after-hyperpolarization. Membrane resistance and firing patterns were studied by applying depolarizing and hyperpolarizing current through the recording electrode. Findings indicate that the NRTP neurone has a relatively high membrane resistance and is capable of firing at a high frequency. Single shock stimulation of the interpositus (IP) and lateral nucleus (LN) of the cerebellum, brachium conjunctivum (BC), red nucleus (RN) and cerebral peduncle (CP) induced monosynaptic EPSPs in the NRTP neurones. Superior vestibular nucleus (SVN) stimulation induced monosynaptic IPSPs. Collision tests showed that (1) NRTP neurones are activated by the axons of IP and LN neurones which travel through BC, (2) these axons also send collaterals to RN, and (3) there is convergence of cerebellar, cerebral and brain stem inputs to a single NRTP neurone."} {"id": "PMID:176046", "title": "Changes in excitability of the theta activity generating substrate by ACTH 4-10 in the rat.", "content": "The present experiments tested the sensitivity of theta activity to ACTH 4-10 a peptide known to facilitate the maintenance of conditioned behaviors. Hippocampal theta activity was induced by electrical stimulation of the reticular formation in freely moving rats. The administration of ACTH 4-10 produced a typical 0.5 c/s shift indominant frequency and an increase in 7.5-9.0 c/s components of induced theta activity. The effects were maximal between 60-120 min after subcutaneous injection and lasted several hours. The fact, that a similar effect could be obtained by an increase in stimulus intensity suggests an elevated excitability in the theta generating system in the presence of the peptide. The possible significance of this finding for the maintenance of learned behavior is discussed.", "contents": "Changes in excitability of the theta activity generating substrate by ACTH 4-10 in the rat. The present experiments tested the sensitivity of theta activity to ACTH 4-10 a peptide known to facilitate the maintenance of conditioned behaviors. Hippocampal theta activity was induced by electrical stimulation of the reticular formation in freely moving rats. The administration of ACTH 4-10 produced a typical 0.5 c/s shift indominant frequency and an increase in 7.5-9.0 c/s components of induced theta activity. The effects were maximal between 60-120 min after subcutaneous injection and lasted several hours. The fact, that a similar effect could be obtained by an increase in stimulus intensity suggests an elevated excitability in the theta generating system in the presence of the peptide. The possible significance of this finding for the maintenance of learned behavior is discussed."} {"id": "PMID:176047", "title": "The lateral reticular nucleus in the cat. IV. Activation from dorsal funiculus and trigeminal afferents.", "content": "1. The activation of neurones in the mLRN (major portion of lateral reticular nucleus comprising its parvi- and magnocellular parts) be a spinal path ascending in the dorsal funiculus (DF) and by trigeminal afferents has been studied. 2. Stimulation of the DF at C3 activated about one half of the mLRN neurones. The latencies were 2-28 ms. In experiments with the spinal cord interrupted at C3 except for the DF it was shown that cutaneous and high threshold muscle afferents in mainly forelimb nerves were effective. The latencies of the responses to nerve stimulation were 8-27 ms. 3. Stimulation of trigeminal afferents evoked a response in about one third of the mLRN neurones. The latencies were 2-27 ms. 4. Activation from the DF- and trigeminal paths occurred often in the same mLRN neurones and the neurones activated from the two paths had a similar location in the nucleus and a similar termination in the cerebellar cortex. 5. The DF- and trigeminal paths had similar properties. Activation was evoked from both ipsilateral and contralateral nerves. Fast adapting hair receptors were commonly effective. 6. Evidence is presented indicating that the DF- and trigeminal paths share a common final path to the mLRN neurones which is formed by brain stem interneurones intercalated between the DF- and trigeminal nuclei and the mLRN. It is suggested that these interneurones represent a supraspinal motor centre. 7. Activation from the DF- and trigeminal paths occurred with unequal frequency among groups of mLRN neurones activated from different spinal paths ascending in the ipsilateral lateral funiculus (cf. Clendenin et al., 1974a).", "contents": "The lateral reticular nucleus in the cat. IV. Activation from dorsal funiculus and trigeminal afferents. 1. The activation of neurones in the mLRN (major portion of lateral reticular nucleus comprising its parvi- and magnocellular parts) be a spinal path ascending in the dorsal funiculus (DF) and by trigeminal afferents has been studied. 2. Stimulation of the DF at C3 activated about one half of the mLRN neurones. The latencies were 2-28 ms. In experiments with the spinal cord interrupted at C3 except for the DF it was shown that cutaneous and high threshold muscle afferents in mainly forelimb nerves were effective. The latencies of the responses to nerve stimulation were 8-27 ms. 3. Stimulation of trigeminal afferents evoked a response in about one third of the mLRN neurones. The latencies were 2-27 ms. 4. Activation from the DF- and trigeminal paths occurred often in the same mLRN neurones and the neurones activated from the two paths had a similar location in the nucleus and a similar termination in the cerebellar cortex. 5. The DF- and trigeminal paths had similar properties. Activation was evoked from both ipsilateral and contralateral nerves. Fast adapting hair receptors were commonly effective. 6. Evidence is presented indicating that the DF- and trigeminal paths share a common final path to the mLRN neurones which is formed by brain stem interneurones intercalated between the DF- and trigeminal nuclei and the mLRN. It is suggested that these interneurones represent a supraspinal motor centre. 7. Activation from the DF- and trigeminal paths occurred with unequal frequency among groups of mLRN neurones activated from different spinal paths ascending in the ipsilateral lateral funiculus (cf. Clendenin et al., 1974a)."} {"id": "PMID:176048", "title": "The effect of morphine on the activity evoked in ventrolateral tract axons of the cat spinal cord.", "content": "The effect of morphine on the activity in ventrolateral tract axons was studied in intercollicularly decerebrate cats with and without spinal section. Activity was elicited by electrical stimulation of Adelta- and C-fibres in the sural nerves. In spinal animals, morphine injected intravenously in a dose as low as 0.5 mg/kg reduced the post-stimulus discharge of impulses recorded in ventrolateral tract axons below the site of transection. The depression was not only abolished but reversed by levallorphan and naloxone. Pretreatment with reserpine did not diminish the effect of morphine. The effect of morphine was considerably weaker in decerebrate cats. Reversible block of the spinal cord produced by cold revealed that morphine reduced inhibition from the brain stem controlling the impulse transmission to ventrolateral tract axons. It is concluded that a spinal effect contributes to the analgesic action of morphine.", "contents": "The effect of morphine on the activity evoked in ventrolateral tract axons of the cat spinal cord. The effect of morphine on the activity in ventrolateral tract axons was studied in intercollicularly decerebrate cats with and without spinal section. Activity was elicited by electrical stimulation of Adelta- and C-fibres in the sural nerves. In spinal animals, morphine injected intravenously in a dose as low as 0.5 mg/kg reduced the post-stimulus discharge of impulses recorded in ventrolateral tract axons below the site of transection. The depression was not only abolished but reversed by levallorphan and naloxone. Pretreatment with reserpine did not diminish the effect of morphine. The effect of morphine was considerably weaker in decerebrate cats. Reversible block of the spinal cord produced by cold revealed that morphine reduced inhibition from the brain stem controlling the impulse transmission to ventrolateral tract axons. It is concluded that a spinal effect contributes to the analgesic action of morphine."} {"id": "PMID:176055", "title": "Does an inhibitor of mitochondrial adenylate kinase also affect oxidative phosphorylation?", "content": "Adenylate kinase activity of intact mitochondria is strongly inhibited by Ap5A, i.e. p1,p5-Di (adenosine-5') pentaphosphate, whereas oxidative phosphorylation is not affected. Therefore, Ap5A is a useful tool to distinguish between oxidative and non oxidative ATP generating reactions.", "contents": "Does an inhibitor of mitochondrial adenylate kinase also affect oxidative phosphorylation? Adenylate kinase activity of intact mitochondria is strongly inhibited by Ap5A, i.e. p1,p5-Di (adenosine-5') pentaphosphate, whereas oxidative phosphorylation is not affected. Therefore, Ap5A is a useful tool to distinguish between oxidative and non oxidative ATP generating reactions."} {"id": "PMID:176056", "title": "Effect of cyclic AMP and theophylline on phagocytotic activity of Tetrahymena pyriformis.", "content": "Dibutyril cAMP and the cPDE-inhibitor theophylline both enhance the phagocytotic activity of Tetrahymena. Theophylline and cAMP-activating histamine are synergistic. It follows that the cAMP-adenylcyclase system functions in the unicellular animal Tetrahymena.", "contents": "Effect of cyclic AMP and theophylline on phagocytotic activity of Tetrahymena pyriformis. Dibutyril cAMP and the cPDE-inhibitor theophylline both enhance the phagocytotic activity of Tetrahymena. Theophylline and cAMP-activating histamine are synergistic. It follows that the cAMP-adenylcyclase system functions in the unicellular animal Tetrahymena."} {"id": "PMID:176057", "title": "Preparation of isolated single cardiac cells from adult frog atrial tissue.", "content": "Isolated cardiac cells from bullfrog atrial tissue can be readily prepared by digestion of intact fragments of atrial tissue with trypsin and collagenase. These isolated cells have dimensions of about 5 mum in width and range in length from 300 mum to over 500 mum. Such isolated cells may prove useful for the investigation of contractile activity of cardiac muscle at the single cell level and at the sarcomere level within the single cell.", "contents": "Preparation of isolated single cardiac cells from adult frog atrial tissue. Isolated cardiac cells from bullfrog atrial tissue can be readily prepared by digestion of intact fragments of atrial tissue with trypsin and collagenase. These isolated cells have dimensions of about 5 mum in width and range in length from 300 mum to over 500 mum. Such isolated cells may prove useful for the investigation of contractile activity of cardiac muscle at the single cell level and at the sarcomere level within the single cell."} {"id": "PMID:176062", "title": "[Influence of lithium chloride on lipid metabolism].", "content": "Lithium chloride was injected subcutaneously to mice (in amounts of 500 and 300 mg/kg) once a day for 10 and 15 days, and to rabbits in single doses via a tube into the stomach (in amounts of 400 and 850 mg/kg). After different time intervals following a single or course-wise administration of the compound the level of total lipids was determined in the muscles and liver of the mice, and of the total lipids, beta-lipoproteins, phospholipids, cholesterol, fatty acids and 11-oxycorticosteroids levels in the blood serum of rabbits and of the bile acids content in the vesical bile of these animals. Hyperlipemia that developed under the effect of lithium was caused by mobilization of fat from fat depots and by deranged interstitial lipids metabolism.", "contents": "[Influence of lithium chloride on lipid metabolism]. Lithium chloride was injected subcutaneously to mice (in amounts of 500 and 300 mg/kg) once a day for 10 and 15 days, and to rabbits in single doses via a tube into the stomach (in amounts of 400 and 850 mg/kg). After different time intervals following a single or course-wise administration of the compound the level of total lipids was determined in the muscles and liver of the mice, and of the total lipids, beta-lipoproteins, phospholipids, cholesterol, fatty acids and 11-oxycorticosteroids levels in the blood serum of rabbits and of the bile acids content in the vesical bile of these animals. Hyperlipemia that developed under the effect of lithium was caused by mobilization of fat from fat depots and by deranged interstitial lipids metabolism."} {"id": "PMID:176068", "title": "[Biochemical correlates of functional features of visual cortex neurons].", "content": "Changes of protein concentration and of different metabolic ferments activity were studied in the rabbit visual cortex after visual deprivation. Two groups of neurons with different sensitivity to visual deprivation were found. The less sensitive are supposed to have an additional source of activation. These findings corroborate the microelectrode data showing that the activity of about 40% of the visual cortex neurons are modulated by a different nonvisual stimulus.", "contents": "[Biochemical correlates of functional features of visual cortex neurons]. Changes of protein concentration and of different metabolic ferments activity were studied in the rabbit visual cortex after visual deprivation. Two groups of neurons with different sensitivity to visual deprivation were found. The less sensitive are supposed to have an additional source of activation. These findings corroborate the microelectrode data showing that the activity of about 40% of the visual cortex neurons are modulated by a different nonvisual stimulus."} {"id": "PMID:176069", "title": "[Antidromic identification of hypothalamic neurosecretory cells which participate in the anterior pituitary control (author's transl)].", "content": "Attempts were made to identify hypothalamic neurosecretory cells which participate in the anterior pituitary control with a special reference to the effects of ovarian hormones. Wave forms of the antidromically activated action potentials in the hypothalamus were investigated in the female rats of Wistar strain. The animals of different endocrinological environments, that is, proestrus and diestrus-I of 4-day cyclers; ovariectomized, ovariectomized and estrogen primed, ovariectomized and progesterone primed, were used. The operational procedures were performed under light urethane anesthesia. Different two types of craniotomy were adopted for the preparation. For recordings from the medial basal hypothalamus, the ventral surface of the brain was exposed by parapharyngeal approach, and a bipolar silver ball electrode for the application of electrical stimuli was placed on the surface of the median eminence (ME). Another method was used for recordings of the medical preoptic area (MPO) and the periventricular area of the MPO and the anterior hypothalamus (PVA). In the latter, the parietal surface of the brain was exposed and a side-by-side bipolar electrode for the stimulation was inserted to the arcuate (ARC-ME region. All the recordings were performed by using glass pipettes which were filled with 0.5 M sodium acetate solution. The solution was added with pontamine sky blue 6B to allow marking recording sites. Stimulatory pulses of 5 msec duration of variable intensity were generated by an electronic stimulator and applied by the above mentioned bipolar electrodes. The antidromic responses and the intensity of the stimuli were observed and photographed on a synchroscope. ...", "contents": "[Antidromic identification of hypothalamic neurosecretory cells which participate in the anterior pituitary control (author's transl)]. Attempts were made to identify hypothalamic neurosecretory cells which participate in the anterior pituitary control with a special reference to the effects of ovarian hormones. Wave forms of the antidromically activated action potentials in the hypothalamus were investigated in the female rats of Wistar strain. The animals of different endocrinological environments, that is, proestrus and diestrus-I of 4-day cyclers; ovariectomized, ovariectomized and estrogen primed, ovariectomized and progesterone primed, were used. The operational procedures were performed under light urethane anesthesia. Different two types of craniotomy were adopted for the preparation. For recordings from the medial basal hypothalamus, the ventral surface of the brain was exposed by parapharyngeal approach, and a bipolar silver ball electrode for the application of electrical stimuli was placed on the surface of the median eminence (ME). Another method was used for recordings of the medical preoptic area (MPO) and the periventricular area of the MPO and the anterior hypothalamus (PVA). In the latter, the parietal surface of the brain was exposed and a side-by-side bipolar electrode for the stimulation was inserted to the arcuate (ARC-ME region. All the recordings were performed by using glass pipettes which were filled with 0.5 M sodium acetate solution. The solution was added with pontamine sky blue 6B to allow marking recording sites. Stimulatory pulses of 5 msec duration of variable intensity were generated by an electronic stimulator and applied by the above mentioned bipolar electrodes. The antidromic responses and the intensity of the stimuli were observed and photographed on a synchroscope. ..."} {"id": "PMID:176070", "title": "[Further purification and immunohistological localization of human placental lactogen in syncytiotrophoblasts (author's transl)].", "content": "In 1936, Ehrhadt reported a prolactin-like substance which has been identified as a second protein hormone exists in extracted substance from the placenta. To date various reports have been published, but ther are still unsolved problems concerning the specifity of the substance, and its clinical significance is unclear. The purpose of this project was to purify and investigate the biochemical, immunological properties of HPL, and try to localize HPL secretion immunohistologically. The biological properties examined by intramuscular and intradermal pigeon crop sac reactions, both showed positive results. Biochemical properties were tested by 7.5% polyacrylamide disc electrophoresis and Free Fatty Acid mobilization. By these methods, the former showed a single band by electrophoresis with purified HPL 200 mug, and the latter showed a strong positive reaction both in vivo and in vitro. Immunological propert iese were examined by immunoelectrophoresis and the Ouchterlony method. In immunoelectrophoresis, the reaction of purified HPL 80 mug and anti-HPL serum resulted in a single strong zone. In constrast, anti-serum and HGH resulted in a weak zone of reaction. We confirmed that HGH cross reacts with our anti-HGH serum to HPL. The cross reaction of HGH with anti-HPL serum was reported by Josimovich et al, and other workers. In the Ouchterlony method, no precipitation line was detected between anti-HPL serum and 50-300 iu of HCG (PREGNYL). The results of investigating the localization of secritions of HPL immunohistologically, show that the specific fluorescence was limited to the strong reacting syncytial layer in the both the early chorionic villi of normal pregnancy and in the late stages of pregnancy. And the results of examining the localization with enzyme reactions with peroxdase from horseradish Type II, the reaction of benzidine brown was limited to the syncytial trophoblastic layer as in the case of FITC. These results suggests that the localization of the secretion of HPL exists in the syncytial layer of the chorionic villi.", "contents": "[Further purification and immunohistological localization of human placental lactogen in syncytiotrophoblasts (author's transl)]. In 1936, Ehrhadt reported a prolactin-like substance which has been identified as a second protein hormone exists in extracted substance from the placenta. To date various reports have been published, but ther are still unsolved problems concerning the specifity of the substance, and its clinical significance is unclear. The purpose of this project was to purify and investigate the biochemical, immunological properties of HPL, and try to localize HPL secretion immunohistologically. The biological properties examined by intramuscular and intradermal pigeon crop sac reactions, both showed positive results. Biochemical properties were tested by 7.5% polyacrylamide disc electrophoresis and Free Fatty Acid mobilization. By these methods, the former showed a single band by electrophoresis with purified HPL 200 mug, and the latter showed a strong positive reaction both in vivo and in vitro. Immunological propert iese were examined by immunoelectrophoresis and the Ouchterlony method. In immunoelectrophoresis, the reaction of purified HPL 80 mug and anti-HPL serum resulted in a single strong zone. In constrast, anti-serum and HGH resulted in a weak zone of reaction. We confirmed that HGH cross reacts with our anti-HGH serum to HPL. The cross reaction of HGH with anti-HPL serum was reported by Josimovich et al, and other workers. In the Ouchterlony method, no precipitation line was detected between anti-HPL serum and 50-300 iu of HCG (PREGNYL). The results of investigating the localization of secritions of HPL immunohistologically, show that the specific fluorescence was limited to the strong reacting syncytial layer in the both the early chorionic villi of normal pregnancy and in the late stages of pregnancy. And the results of examining the localization with enzyme reactions with peroxdase from horseradish Type II, the reaction of benzidine brown was limited to the syncytial trophoblastic layer as in the case of FITC. These results suggests that the localization of the secretion of HPL exists in the syncytial layer of the chorionic villi."} {"id": "PMID:176076", "title": "Virus-induced diabetes mellitus. IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalomyocarditis virus.", "content": "The M variant of encephalomyocarditis virus (EMC) infects pancreatic beta cells and causes the development of a diabetic syndrome in susceptible strains of mice. By examining four F1 crosses of susceptible and resistant strains of mice, we found that the development of diabetes after infection was inherited as a recessive trait. Analysis of the data from the F2 generation indicated that more than one gene was involved in the development of EMC-diabetes. The severity and frequency of abnormal glucose levels in EMC-infected animals was markedly influenced by environmental factors.", "contents": "Virus-induced diabetes mellitus. IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalomyocarditis virus. The M variant of encephalomyocarditis virus (EMC) infects pancreatic beta cells and causes the development of a diabetic syndrome in susceptible strains of mice. By examining four F1 crosses of susceptible and resistant strains of mice, we found that the development of diabetes after infection was inherited as a recessive trait. Analysis of the data from the F2 generation indicated that more than one gene was involved in the development of EMC-diabetes. The severity and frequency of abnormal glucose levels in EMC-infected animals was markedly influenced by environmental factors."} {"id": "PMID:176077", "title": "Influence of cell size on the effects of insulin and noradrenaline on human adipose tissue.", "content": "In the present study dose-response relationships of the effects of noradrenaline and insulin on fat cells of different sizes were performed. Adipose cells larger than 100 mum were more responsive (expressed as absolute effects) to the lipolytic action of noradrenaline as well as to the antilipolytic effect of insulin. This suggests that in the larger cells the capacity, i.e. the sum of factors contributing to the ability to stimulate or inhibit the metabolic rates, was greater than in the smaller ones. In contrast the sensitivity to these agents, i.e. the readiness to respond, was not different between small and large cells. It is shown that the concentrations of insulin needed to obtain an antilipolytic effect is far below that needed to stimulate glucose incorporation. This discrepancy in insulin concentrations required may be due to binding of insulin to receptors with different affinity.", "contents": "Influence of cell size on the effects of insulin and noradrenaline on human adipose tissue. In the present study dose-response relationships of the effects of noradrenaline and insulin on fat cells of different sizes were performed. Adipose cells larger than 100 mum were more responsive (expressed as absolute effects) to the lipolytic action of noradrenaline as well as to the antilipolytic effect of insulin. This suggests that in the larger cells the capacity, i.e. the sum of factors contributing to the ability to stimulate or inhibit the metabolic rates, was greater than in the smaller ones. In contrast the sensitivity to these agents, i.e. the readiness to respond, was not different between small and large cells. It is shown that the concentrations of insulin needed to obtain an antilipolytic effect is far below that needed to stimulate glucose incorporation. This discrepancy in insulin concentrations required may be due to binding of insulin to receptors with different affinity."} {"id": "PMID:176078", "title": "Axyl hydrocarbon hydroxylase in Morris hepatoma 5123D.", "content": "Aryl hydrocarbon hydroxylase activity in Morris hepatoma 5123D is very low, but apparently increases by the administration of 3-methylcholanthrene, as demonstrated in the host liver, small intestine, and lung from the rats bearing this tumor. The peak level of the increased activity in tumor appears 48 hr after the initial administration when the repeated treatment is given intragastrically every 24 hr. 7,8-Benzoflavone increases the enzyme activity in tumor and lung, but not in liver and small intestine. Among the subcellular fractions of the tumor cells, induction of the enzyme by 3-methylcholanthrene was observed in microsomes and nuclei, and the increased level of the activity was higher in microsomes than in nuclei.", "contents": "Axyl hydrocarbon hydroxylase in Morris hepatoma 5123D. Aryl hydrocarbon hydroxylase activity in Morris hepatoma 5123D is very low, but apparently increases by the administration of 3-methylcholanthrene, as demonstrated in the host liver, small intestine, and lung from the rats bearing this tumor. The peak level of the increased activity in tumor appears 48 hr after the initial administration when the repeated treatment is given intragastrically every 24 hr. 7,8-Benzoflavone increases the enzyme activity in tumor and lung, but not in liver and small intestine. Among the subcellular fractions of the tumor cells, induction of the enzyme by 3-methylcholanthrene was observed in microsomes and nuclei, and the increased level of the activity was higher in microsomes than in nuclei."} {"id": "PMID:176079", "title": "Inhibition of multinucleation of cells treated with cytochalasin-B by cyclic dibutyryl-AMP.", "content": "Multinucleation of SV40-transformed mouse cells was induced by Cytochalasin-B as a result of inhibition of cytokinesis. Multinucleated cells with nuclei, whose number is other than that that can be obtained by raising the power of 2, were frequently observed. By simultaneous addition of Cytochalasin-B and cylic dibutyryl-AMP to SV40-transformad mouse cellls, multinucleation was fairly inhibited and the predominance of the cells with 2 or 4 nuclei was characteristic. In case of normal mouse cells (BALB/3T3), addition of both Cytochalasin-B and cyclic dibutyryl-AMP lessened the number of nucleic in a cell compared with treatment of the cells with Cytochalasin-B alone. These results suggested that cyclic dibutyryl-AMP inhibited multinucleation of cells treated with Cytochalasin-B and that the chemical regulated the division of nuclei in a cell to divide simultaneously.", "contents": "Inhibition of multinucleation of cells treated with cytochalasin-B by cyclic dibutyryl-AMP. Multinucleation of SV40-transformed mouse cells was induced by Cytochalasin-B as a result of inhibition of cytokinesis. Multinucleated cells with nuclei, whose number is other than that that can be obtained by raising the power of 2, were frequently observed. By simultaneous addition of Cytochalasin-B and cylic dibutyryl-AMP to SV40-transformad mouse cellls, multinucleation was fairly inhibited and the predominance of the cells with 2 or 4 nuclei was characteristic. In case of normal mouse cells (BALB/3T3), addition of both Cytochalasin-B and cyclic dibutyryl-AMP lessened the number of nucleic in a cell compared with treatment of the cells with Cytochalasin-B alone. These results suggested that cyclic dibutyryl-AMP inhibited multinucleation of cells treated with Cytochalasin-B and that the chemical regulated the division of nuclei in a cell to divide simultaneously."} {"id": "PMID:176080", "title": "Bicarbonate and cyclic AMP content of pure human pancreatic juice in response to graded doses of synthetic secretin.", "content": "In seven healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the papilla of Vater. Synthetic secretin was intravenously infused in doses doubled every 20 min. The volume of pancreatic juice was proportional to the log of the secretin dose. A significant rise (P less than 0.05) in pancreatic juice flow was elicited at a dose as low as 8.05 ng per kg per hr. Maximum flow rate approximating 250 mul per 5 min per kg of body weight was attained during infusion of 129 ng per kg per hr. At the same dose maximal bicarbonate outputs averaging 383 muEq per hr per kg of body weight were obtained, whereas bicarbonate ion concentration approached peak values (135 +/- 9 muEq per ml) at 32.2 ng per kg per hr. Bicarbonate concentrations showed a tendency to fall at supramaximal doses. The effect of increasing secretin doses on bicarbonate and cyclic AMP concentrations was remarkably similar (rs = 0.635, P less than 0.001) suggesting the participation of cyclic AMP in human pancreatic bicarbonate secretion.", "contents": "Bicarbonate and cyclic AMP content of pure human pancreatic juice in response to graded doses of synthetic secretin. In seven healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the papilla of Vater. Synthetic secretin was intravenously infused in doses doubled every 20 min. The volume of pancreatic juice was proportional to the log of the secretin dose. A significant rise (P less than 0.05) in pancreatic juice flow was elicited at a dose as low as 8.05 ng per kg per hr. Maximum flow rate approximating 250 mul per 5 min per kg of body weight was attained during infusion of 129 ng per kg per hr. At the same dose maximal bicarbonate outputs averaging 383 muEq per hr per kg of body weight were obtained, whereas bicarbonate ion concentration approached peak values (135 +/- 9 muEq per ml) at 32.2 ng per kg per hr. Bicarbonate concentrations showed a tendency to fall at supramaximal doses. The effect of increasing secretin doses on bicarbonate and cyclic AMP concentrations was remarkably similar (rs = 0.635, P less than 0.001) suggesting the participation of cyclic AMP in human pancreatic bicarbonate secretion."} {"id": "PMID:176081", "title": "Cyclic AMP in secretin choleresis. Evidence for a regulatory role in man and baboons but not in dogs.", "content": "Cyclic AMP output in the bile in response to intravenous secretin was measured in 11 patients, 12 baboons, and 15 dogs. Secretin was given to patients with bile drainage tubes as an intravenous bolus (1 U per kg). In baboons and dogs both secretin infusion (4 U per kg per hr) and bolus injection (1 U per kg) were used. In baboons cyclic AMP was also determined in liver, extrahepatic duct tissue, and in perfusate from isolated segments of extrahepatic bile ducts. Secretin induced a marked choleresis in all three species. In humans, biliary cyclic AMP concentration increased an average (+/- 1 SE) of 68% +/- 12% and in baboons 4-fold, but no increase occurred in dogs. In baboons, cyclic AMP concentration increased in both bile duct tissue and perfusate from isolated bile ducts concomitant with secretin choleresis, but not in liver. In humans the choleretic effects of sodium dehydrocholate, aminophylline, and glucagon were compared to dibutyryl cyclic AMP (DBcyclic AMP). All agents increased bile flow 2- to 3-fold. Cyclic AMP concentration in bile markedly increased after glucagon and DBcyclic AMP but not after sodium dehydrocholate and aminophylline. We conclude that cyclic AMP is implicated in secretin choleresis in both humans and baboons, but not in dogs. The bile duct appears to be the site of cyclic AMP elaboration induced by secretin in baboons and probably is also in man.", "contents": "Cyclic AMP in secretin choleresis. Evidence for a regulatory role in man and baboons but not in dogs. Cyclic AMP output in the bile in response to intravenous secretin was measured in 11 patients, 12 baboons, and 15 dogs. Secretin was given to patients with bile drainage tubes as an intravenous bolus (1 U per kg). In baboons and dogs both secretin infusion (4 U per kg per hr) and bolus injection (1 U per kg) were used. In baboons cyclic AMP was also determined in liver, extrahepatic duct tissue, and in perfusate from isolated segments of extrahepatic bile ducts. Secretin induced a marked choleresis in all three species. In humans, biliary cyclic AMP concentration increased an average (+/- 1 SE) of 68% +/- 12% and in baboons 4-fold, but no increase occurred in dogs. In baboons, cyclic AMP concentration increased in both bile duct tissue and perfusate from isolated bile ducts concomitant with secretin choleresis, but not in liver. In humans the choleretic effects of sodium dehydrocholate, aminophylline, and glucagon were compared to dibutyryl cyclic AMP (DBcyclic AMP). All agents increased bile flow 2- to 3-fold. Cyclic AMP concentration in bile markedly increased after glucagon and DBcyclic AMP but not after sodium dehydrocholate and aminophylline. We conclude that cyclic AMP is implicated in secretin choleresis in both humans and baboons, but not in dogs. The bile duct appears to be the site of cyclic AMP elaboration induced by secretin in baboons and probably is also in man."} {"id": "PMID:176082", "title": "Effects of cholera enterotoxin, glucagon, and dibutyryl cyclic AMP on rat liver alkaline phosphatase, bile flow, and bile composition.", "content": "Cholera enterotoxin, 45 mug per 250 g body weight, administered intravenously to rats, caused a 6-fold rise in the activity of liver alkaline phosphatase in 12 hr. There was no change in bile volume or in the concentration or total bile content of Na+, K+, HCO3-, or Cl- for 36 hr after the administration of cholera toxin. However, bile phospholipid output fell markedly from a control level of 15.0 +/- 1.0 mumol per 6 hr to a low level of 4.0 +/- 1.2 mumol per 6 hr in the 12- to 18-hr collection, P less than 0.001. There was a similar fall in bile acid secretion, from a control value of 9.8 +/- 0.4 mumol per 6 hr to 4.1 +/- 0.9 mumol in the 12- to 18-hr period, P less than 0.01. The cholera effect was prolonged. Bile acid and phospholipid secretion rates did not return to control values until 30 to 36 hr after the administration of cholera enterotoxin. The cholera toxin-induced reductions in bile acid and phospholipid secretion into bile did not appear to be mediated by adenyl cyclase or cyclic AMP because neither glucagon, a known stimulator of liver adenyl cyclase, nor dibutyryl cyclic AMP had any effect on the secretion into bile of bile acids or phospholipid. The administration of cholera toxin was not associated with any increase in the secretion of free choline into bile. Glucagon and dibutyryl cyclic AMP, two other substances known to increase the activity of rat liver alkaline phosphatase, also had no stimulatory effect on the secretion of free choline into bile. The results do not support the hypothesis that the main function of rat liver alkaline phosphatase is to facilitate the excretion of free choline into bile.", "contents": "Effects of cholera enterotoxin, glucagon, and dibutyryl cyclic AMP on rat liver alkaline phosphatase, bile flow, and bile composition. Cholera enterotoxin, 45 mug per 250 g body weight, administered intravenously to rats, caused a 6-fold rise in the activity of liver alkaline phosphatase in 12 hr. There was no change in bile volume or in the concentration or total bile content of Na+, K+, HCO3-, or Cl- for 36 hr after the administration of cholera toxin. However, bile phospholipid output fell markedly from a control level of 15.0 +/- 1.0 mumol per 6 hr to a low level of 4.0 +/- 1.2 mumol per 6 hr in the 12- to 18-hr collection, P less than 0.001. There was a similar fall in bile acid secretion, from a control value of 9.8 +/- 0.4 mumol per 6 hr to 4.1 +/- 0.9 mumol in the 12- to 18-hr period, P less than 0.01. The cholera effect was prolonged. Bile acid and phospholipid secretion rates did not return to control values until 30 to 36 hr after the administration of cholera enterotoxin. The cholera toxin-induced reductions in bile acid and phospholipid secretion into bile did not appear to be mediated by adenyl cyclase or cyclic AMP because neither glucagon, a known stimulator of liver adenyl cyclase, nor dibutyryl cyclic AMP had any effect on the secretion into bile of bile acids or phospholipid. The administration of cholera toxin was not associated with any increase in the secretion of free choline into bile. Glucagon and dibutyryl cyclic AMP, two other substances known to increase the activity of rat liver alkaline phosphatase, also had no stimulatory effect on the secretion of free choline into bile. The results do not support the hypothesis that the main function of rat liver alkaline phosphatase is to facilitate the excretion of free choline into bile."} {"id": "PMID:176083", "title": "[Present problems of somatic cell genetics].", "content": "A review of recent advances in genetics of somatic cells is given in the article. It contains three sections: 1) hybridization of somatic cells and its application to the mapping of genes and to the study of gene action; 2) relation of somatic cell genetics to genetic engineerings; 3) progress and perspectives of higher plant somatic cell genetics.", "contents": "[Present problems of somatic cell genetics]. A review of recent advances in genetics of somatic cells is given in the article. It contains three sections: 1) hybridization of somatic cells and its application to the mapping of genes and to the study of gene action; 2) relation of somatic cell genetics to genetic engineerings; 3) progress and perspectives of higher plant somatic cell genetics."} {"id": "PMID:176087", "title": "[A case of endogenous familial hereditary malformation of both hands].", "content": "A case of congenital malformation of both hands in a 22 year old television-technician, who otherwise showed no abnormalities, is reported. In his case, a familiar incidence was observed constantly in all males for a period of nearly 200 years. The morphological picture of this malformation is as follows: left hand: postaxial oligodactyly with a cutaneous syndactyly of the third and fourth fingers accompanied by a V-shaped os metacarpale and a synostosis of the os triquetrum, os lunatum and possibly of the os pisiforme right hand: postaxial oligodactyly with an accessory hypoplastic third finger on the ulnar side with a common base of the proximal phalanx which was enlarged at the end and shorter than the others (symbrachybasophalanx). Os multangulum minus and os capitatum as well as os triquetrum and possibly also the os pisiforme showed a synostosis. Subjective symptomatology and further clinical investigations (Phonocardiogramm) revealed an associated heart disease. This kind of malformation of both hands is transmitted inclompletely only in males.", "contents": "[A case of endogenous familial hereditary malformation of both hands]. A case of congenital malformation of both hands in a 22 year old television-technician, who otherwise showed no abnormalities, is reported. In his case, a familiar incidence was observed constantly in all males for a period of nearly 200 years. The morphological picture of this malformation is as follows: left hand: postaxial oligodactyly with a cutaneous syndactyly of the third and fourth fingers accompanied by a V-shaped os metacarpale and a synostosis of the os triquetrum, os lunatum and possibly of the os pisiforme right hand: postaxial oligodactyly with an accessory hypoplastic third finger on the ulnar side with a common base of the proximal phalanx which was enlarged at the end and shorter than the others (symbrachybasophalanx). Os multangulum minus and os capitatum as well as os triquetrum and possibly also the os pisiforme showed a synostosis. Subjective symptomatology and further clinical investigations (Phonocardiogramm) revealed an associated heart disease. This kind of malformation of both hands is transmitted inclompletely only in males."} {"id": "PMID:176088", "title": "[Preliminary report on the follow-up examination of 101 surgical cases of syndactylia].", "content": "A review of 48 patients in whom 101 syndactyly separations were performed between 1963 and 1972 is reported with the peaks of frequency of the inital operation (being in early infancy, and just before entering school). Different surgical techniques were used for restoration of the web space, with the two-flap-technique of ZELLER most often used. About 60% of the fingers were separated by longitudinal incisions with the remaining 40% with zig-zag incisions. Of the skin grafts, about two-thirds showed excellent cosmetic appearance with the remaining third showing evidence of hyperpigmentation. Digital abduction was measured and approximated the spread seen in normal children.", "contents": "[Preliminary report on the follow-up examination of 101 surgical cases of syndactylia]. A review of 48 patients in whom 101 syndactyly separations were performed between 1963 and 1972 is reported with the peaks of frequency of the inital operation (being in early infancy, and just before entering school). Different surgical techniques were used for restoration of the web space, with the two-flap-technique of ZELLER most often used. About 60% of the fingers were separated by longitudinal incisions with the remaining 40% with zig-zag incisions. Of the skin grafts, about two-thirds showed excellent cosmetic appearance with the remaining third showing evidence of hyperpigmentation. Digital abduction was measured and approximated the spread seen in normal children."} {"id": "PMID:176094", "title": "[A comparison of xero-tomography of the lung hilum with conventional tomography (author's transl)].", "content": "Because of its particular photoelectric properties, xero-tomography is particularly suited for the investigation of abnormalities in the hilar regions. It is superior to conventional tomography because of the improved edge contrast, which emphasises details of relatively non-opaque structures, and because of its high exposure latitude. This justifies its use despite the higher radiation dose that is necessary. The demonstration of relatively dense and of more transradient tissues on the same picture by xero-tomography, and the ability to read it by ordinary light, makes it less tiring to interpret than the translucencies of conventional radiographs.", "contents": "[A comparison of xero-tomography of the lung hilum with conventional tomography (author's transl)]. Because of its particular photoelectric properties, xero-tomography is particularly suited for the investigation of abnormalities in the hilar regions. It is superior to conventional tomography because of the improved edge contrast, which emphasises details of relatively non-opaque structures, and because of its high exposure latitude. This justifies its use despite the higher radiation dose that is necessary. The demonstration of relatively dense and of more transradient tissues on the same picture by xero-tomography, and the ability to read it by ordinary light, makes it less tiring to interpret than the translucencies of conventional radiographs."} {"id": "PMID:176095", "title": "Bone scanning with 99m-Tc-phosphates: a comparison and problems in the detection of tumor metastasis.", "content": "A comparative study on 99m-Tc-phosphate compounds (TcPP) in detecting tumor metastasis to bone and problems accompanying it are reported. TcPP revealed metastatic foci which are unrecognized by conventional bone survey. To recognize these foci, exclusion of following problems is necessary: Accumulation at front of neck, asymmetrical image of joint, increased bone density of the aged, Tc-photon absorption and radiotherapy effect. The mechanism of TcPP accumulation is discussed.", "contents": "Bone scanning with 99m-Tc-phosphates: a comparison and problems in the detection of tumor metastasis. A comparative study on 99m-Tc-phosphate compounds (TcPP) in detecting tumor metastasis to bone and problems accompanying it are reported. TcPP revealed metastatic foci which are unrecognized by conventional bone survey. To recognize these foci, exclusion of following problems is necessary: Accumulation at front of neck, asymmetrical image of joint, increased bone density of the aged, Tc-photon absorption and radiotherapy effect. The mechanism of TcPP accumulation is discussed."} {"id": "PMID:176096", "title": "[Angiographic findings of a mixed angiodysplasia (Klippel-Trenaunay-Weber syndrome) associated with choanal atresia (author's transl)].", "content": "The angiographic, phlebographic and lymphographic findings in a 3-year old girl with mixed angiodysplasia (Klippel-Trenaunay-Weber syndrome) combined with unilateral congenital choanal atresia are described.", "contents": "[Angiographic findings of a mixed angiodysplasia (Klippel-Trenaunay-Weber syndrome) associated with choanal atresia (author's transl)]. The angiographic, phlebographic and lymphographic findings in a 3-year old girl with mixed angiodysplasia (Klippel-Trenaunay-Weber syndrome) combined with unilateral congenital choanal atresia are described."} {"id": "PMID:176097", "title": "[Percutaneous recanalisation of chronic arterial occlusions (Dotter principle) with a new double lumen dilatation catheter (author's transl)].", "content": "A modification of Dotter's transluminal recanalisation of stenoses and occlusions of the superficial femoral artery, and of stenoses of the iliac artery, is described. In this procedure the occluding material is compressed not by successive catheters, but by a catheter with a dilatable cover. This catheter consisted originally of a single lumen, but now has double lumen; one lumen accomodates contrast, or a guide wire or a stiff cannula, whereas the second lumen is used for filling the cover and the expandable segment. The procedure is described in detail. Results so far appear satisfactory; they are compared with the results which have been obtained during the last year with the single lumen catheter.", "contents": "[Percutaneous recanalisation of chronic arterial occlusions (Dotter principle) with a new double lumen dilatation catheter (author's transl)]. A modification of Dotter's transluminal recanalisation of stenoses and occlusions of the superficial femoral artery, and of stenoses of the iliac artery, is described. In this procedure the occluding material is compressed not by successive catheters, but by a catheter with a dilatable cover. This catheter consisted originally of a single lumen, but now has double lumen; one lumen accomodates contrast, or a guide wire or a stiff cannula, whereas the second lumen is used for filling the cover and the expandable segment. The procedure is described in detail. Results so far appear satisfactory; they are compared with the results which have been obtained during the last year with the single lumen catheter."} {"id": "PMID:176101", "title": "[Mode of fatty acid synthesis in rat liver mitochondria (author's transl)].", "content": "In order to clarify the mode of fatty acid synthesis in rat liver mitochondria, metabolism of labeled fatty acid was examined after portal and intraperitoneal administration of several labeled fatty acids. 1) After portal administration of palmitic acid-1-14C, alpha, beta-mono-unsaturated fatty acid (C18:1) was synthesized as a result of chain elongation by addition of endogenous C2 compound 20 min. after injection. 2) Similarly, after lauric acid-1-14C injection, myristic acid (C14) and palmitic acid (C16) were found 20 min. after injection and even C18:2 was detected 30 min. after injection. 3) Following intraperitoneal administration of lauric acid-1-14C, the appearance of palmitic acid (C16) was confirmed in inner mitochondrial membranes 60 min. after injection. From the analysis of intramolecular distribution of labeled carbon, it is surmised that lauric acid is first decomposed into C2 fragments which then are used for the chain elongation.", "contents": "[Mode of fatty acid synthesis in rat liver mitochondria (author's transl)]. In order to clarify the mode of fatty acid synthesis in rat liver mitochondria, metabolism of labeled fatty acid was examined after portal and intraperitoneal administration of several labeled fatty acids. 1) After portal administration of palmitic acid-1-14C, alpha, beta-mono-unsaturated fatty acid (C18:1) was synthesized as a result of chain elongation by addition of endogenous C2 compound 20 min. after injection. 2) Similarly, after lauric acid-1-14C injection, myristic acid (C14) and palmitic acid (C16) were found 20 min. after injection and even C18:2 was detected 30 min. after injection. 3) Following intraperitoneal administration of lauric acid-1-14C, the appearance of palmitic acid (C16) was confirmed in inner mitochondrial membranes 60 min. after injection. From the analysis of intramolecular distribution of labeled carbon, it is surmised that lauric acid is first decomposed into C2 fragments which then are used for the chain elongation."} {"id": "PMID:176102", "title": "[Fractionation of inner and outer mitochondrial membranes in rat liver (author's transl)].", "content": "Mitochondrial membranes of rat liver were fractionated into inner and outer membranes by osmotic shock. Purity of the inner and outer membrane subfractions was examined by estimating marker enzyme activities of succinate-cytochrome c reductase and monoamine oxidase, respectively. Monoamine oxidase activity in the outer membrane subfraction was found to be 21.90 mmumoles of benzaldehyde produced/min./mg. protein and 1.57 mmumoles in the inner membranes, whereas succinate-cytochrome c reductase activity was 13.4 and 33.0 mmumoles/min./mg. protein, respectively. These results indicate higher purity of each membrane fraction obtained.", "contents": "[Fractionation of inner and outer mitochondrial membranes in rat liver (author's transl)]. Mitochondrial membranes of rat liver were fractionated into inner and outer membranes by osmotic shock. Purity of the inner and outer membrane subfractions was examined by estimating marker enzyme activities of succinate-cytochrome c reductase and monoamine oxidase, respectively. Monoamine oxidase activity in the outer membrane subfraction was found to be 21.90 mmumoles of benzaldehyde produced/min./mg. protein and 1.57 mmumoles in the inner membranes, whereas succinate-cytochrome c reductase activity was 13.4 and 33.0 mmumoles/min./mg. protein, respectively. These results indicate higher purity of each membrane fraction obtained."} {"id": "PMID:176103", "title": "Investigations on isolated islets of Langerhans in vitro. Influence of temperature changes during preparation on some parameters of insulin metabolism.", "content": "Pancreatic islets of Wistar rats were prepared by digestion with collagenase and then washed and isolated at three different temperatures (4, 22 and 37 degrees C). The efficiency of washing with regard to proteolytic and collagenolytic activities in the wash buffer was not affected by the temperatures used. The islet thiol:protein-disulphide oxidoreductase activity (EC 1.8.4.2) was apparently unchanged, whereas washing temperatures lower than 37 degrees C resulted in a diminished insulin content. The insulin secretion of islets, isolated at 4 degrees C, is reduced in response to glucose without changing the sigmoidal shape of dose-response curve.", "contents": "Investigations on isolated islets of Langerhans in vitro. Influence of temperature changes during preparation on some parameters of insulin metabolism. Pancreatic islets of Wistar rats were prepared by digestion with collagenase and then washed and isolated at three different temperatures (4, 22 and 37 degrees C). The efficiency of washing with regard to proteolytic and collagenolytic activities in the wash buffer was not affected by the temperatures used. The islet thiol:protein-disulphide oxidoreductase activity (EC 1.8.4.2) was apparently unchanged, whereas washing temperatures lower than 37 degrees C resulted in a diminished insulin content. The insulin secretion of islets, isolated at 4 degrees C, is reduced in response to glucose without changing the sigmoidal shape of dose-response curve."} {"id": "PMID:176115", "title": "Long-term follow-up studies on herpes simplex antibodies in the course of cervical cancer. II. Antibodies to surface antigen of Herpes simplex virus infected cells.", "content": "In a serological follow-up of 88 women with active invasive cervical carcinoma, antibodies to membrane antigen of Herpes simplex virus (HSV)-infected cells were measured by the use of the mixed hemadsorption method. Sera were collected at the time of initial treatment and then at regular intervals. As controls, 85 healthy age-matched women and 70 patients suffering from other types of cancer were tested similarly. During the 6-to 60-month observation period 16 patients in the cervix carcinoma group died. The reactivity with membrane antigen of HSV-infected cells was positive in 71% of the cervical carcinoma patients, whereas the figure for the other cancer group was 27% and for the age-matched control group 27%. In the group of 16 patients who died, only 3 demonstrated antibodies against surface antigens of HSV-infected cells. In most cases radiation treatment of the tumor did not significantly alter the mixed hemadsorption titer but in 10 surviving patients there was a significant increase in reactivity as the tumor was treated; 1 patient who had recurrence of her cancer lost reactivity in later sera. Among the 11 cervix carcinoma patients in stage I (by clinical definition carcinoma strictly confined to the cervix) all but one showed positive reaction against the surface antigen of HSV-infected cells; the patient lacking reactivity was the only one out of the 11 patients in stage I who had a recurrence of her cancer. The results confirm that low or missing antibody titers to membrane antigen of HSV-infected cells are of prognostic significance, and decreasing antibody titers to membrane antigens run parallel to the severity of the lesions. There was poor correlation between antibody titers against membrane antigens and neutralizing antibody titers.", "contents": "Long-term follow-up studies on herpes simplex antibodies in the course of cervical cancer. II. Antibodies to surface antigen of Herpes simplex virus infected cells. In a serological follow-up of 88 women with active invasive cervical carcinoma, antibodies to membrane antigen of Herpes simplex virus (HSV)-infected cells were measured by the use of the mixed hemadsorption method. Sera were collected at the time of initial treatment and then at regular intervals. As controls, 85 healthy age-matched women and 70 patients suffering from other types of cancer were tested similarly. During the 6-to 60-month observation period 16 patients in the cervix carcinoma group died. The reactivity with membrane antigen of HSV-infected cells was positive in 71% of the cervical carcinoma patients, whereas the figure for the other cancer group was 27% and for the age-matched control group 27%. In the group of 16 patients who died, only 3 demonstrated antibodies against surface antigens of HSV-infected cells. In most cases radiation treatment of the tumor did not significantly alter the mixed hemadsorption titer but in 10 surviving patients there was a significant increase in reactivity as the tumor was treated; 1 patient who had recurrence of her cancer lost reactivity in later sera. Among the 11 cervix carcinoma patients in stage I (by clinical definition carcinoma strictly confined to the cervix) all but one showed positive reaction against the surface antigen of HSV-infected cells; the patient lacking reactivity was the only one out of the 11 patients in stage I who had a recurrence of her cancer. The results confirm that low or missing antibody titers to membrane antigen of HSV-infected cells are of prognostic significance, and decreasing antibody titers to membrane antigens run parallel to the severity of the lesions. There was poor correlation between antibody titers against membrane antigens and neutralizing antibody titers."} {"id": "PMID:176116", "title": "Transformation-enhancing factor(s) produced by virus-transformed and established cells.", "content": "Chick embryo fibroblasts (CEF) and hamster BHK21 cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) release into the culture medium a factor or factors which enhance 2- to 7-fold the formation of transformed foci by chich embryo fibroblasts infected with the Bryan strain of RSV (B-RSV). The factor(s) also increase the number of foci failing to revert to normal phenotype at restrictive temperature (41 degrees C) in cultures infected with a temperature-sensitive mutant (FU-19) of SR-RSV which is defective for transformation. The factor(s) is produced also by BHK21 cells transformed by other tumor viruses and by BHK21 cells passaged for a long time, but not by normal CEF, CEF transformed by B-RSV, CEF infected by FU-19 at 41 degrees C, normal hamster embryo fibroblasts, established but density-inhibited mouse fibroblasts, or BHK21 cells of early passages. The relative enhancement of the number of B-RSV foci can be more than 100-fold when the medium contains fetal calf serum which suppresses focus formation in controls. The focus-enhacing factor(s) appears to act after infection and has been termed, operationally, transformation-enhancing factor(s) or TEF. The factor produced by RS2/3 cells which enhances the formation of B-RSV foci is non-dialyzable and thermolabile, and is presumably a protein. Its molecular weight is between 10(5) and 2 X 10(5) daltons.", "contents": "Transformation-enhancing factor(s) produced by virus-transformed and established cells. Chick embryo fibroblasts (CEF) and hamster BHK21 cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) release into the culture medium a factor or factors which enhance 2- to 7-fold the formation of transformed foci by chich embryo fibroblasts infected with the Bryan strain of RSV (B-RSV). The factor(s) also increase the number of foci failing to revert to normal phenotype at restrictive temperature (41 degrees C) in cultures infected with a temperature-sensitive mutant (FU-19) of SR-RSV which is defective for transformation. The factor(s) is produced also by BHK21 cells transformed by other tumor viruses and by BHK21 cells passaged for a long time, but not by normal CEF, CEF transformed by B-RSV, CEF infected by FU-19 at 41 degrees C, normal hamster embryo fibroblasts, established but density-inhibited mouse fibroblasts, or BHK21 cells of early passages. The relative enhancement of the number of B-RSV foci can be more than 100-fold when the medium contains fetal calf serum which suppresses focus formation in controls. The focus-enhacing factor(s) appears to act after infection and has been termed, operationally, transformation-enhancing factor(s) or TEF. The factor produced by RS2/3 cells which enhances the formation of B-RSV foci is non-dialyzable and thermolabile, and is presumably a protein. Its molecular weight is between 10(5) and 2 X 10(5) daltons."} {"id": "PMID:176117", "title": "Kinetics of serum factors mediating blocking, unblocking and antibody-dependent cellular cytotoxicity in hamsters given isografts of para-7 tumor cells.", "content": "Sera collected at intervals after PARA-7 tumor-cell inoculation were monitored for blocking, unblocking, and antibody-dependent cellular cytotoxicity (ADCC) using the microcytotoxicity test. Within 7 days after isografting, significant levels of blocking were demonstrated. This activity increased in parallel with tumor growth and reached a maximum at day 21. In contrast, the capacity of the sera to mediate ADCC was maximal at day 7, and no longer detectable at 3 weeks. Unblocking was not demonstrable in tumor-bearer sera. Further studies showed that, when the tumor was exicised, blocking activity fell rapidly while ADCC was elevated. Sera collected 7 days after surgery could neutralize the blocking activity of tumor-bearer sera. Significant levels of unblocking were still evident 10 weeks after surgery while ADCC had generally disappeared after 5 weeks. These findings illustrate the complexity of the hamster's humoral immune response to tumor cells, and suggest that (1) the sequestering of antibody by circulating tumor antigen accounts for the demise of ADCC in tumor-bearer sera and the concomitant appearance of blocking activity; and (2) the serum factors mediating ADCC and unblocking differ.", "contents": "Kinetics of serum factors mediating blocking, unblocking and antibody-dependent cellular cytotoxicity in hamsters given isografts of para-7 tumor cells. Sera collected at intervals after PARA-7 tumor-cell inoculation were monitored for blocking, unblocking, and antibody-dependent cellular cytotoxicity (ADCC) using the microcytotoxicity test. Within 7 days after isografting, significant levels of blocking were demonstrated. This activity increased in parallel with tumor growth and reached a maximum at day 21. In contrast, the capacity of the sera to mediate ADCC was maximal at day 7, and no longer detectable at 3 weeks. Unblocking was not demonstrable in tumor-bearer sera. Further studies showed that, when the tumor was exicised, blocking activity fell rapidly while ADCC was elevated. Sera collected 7 days after surgery could neutralize the blocking activity of tumor-bearer sera. Significant levels of unblocking were still evident 10 weeks after surgery while ADCC had generally disappeared after 5 weeks. These findings illustrate the complexity of the hamster's humoral immune response to tumor cells, and suggest that (1) the sequestering of antibody by circulating tumor antigen accounts for the demise of ADCC in tumor-bearer sera and the concomitant appearance of blocking activity; and (2) the serum factors mediating ADCC and unblocking differ."} {"id": "PMID:176118", "title": "Cell-killing by Epstein-Barr virus: analysis by colony inhibition procedure.", "content": "The P3HR-1 and B95-8 strains of Epstein-Barr virus (EBV) were cytocidal for EBV-carrier human cell lines, as revealed by a colony inhibition procedure. The cytocidal activity was proportional to virus dose added. The cell killing was neutralized by anti-EBV antibody-positive but not -negative human sera. When the relative sensitivity to ultraviolet light of EBV activities was examined, the cytocidal actitivy was much more resistant than the viral infectivity as assayed by early antigen-forming activity (P3HR-1 virus) or leukocyte-transforming activity (B95-8 virus), but it closely paralleled the ability to adsorb to cells.", "contents": "Cell-killing by Epstein-Barr virus: analysis by colony inhibition procedure. The P3HR-1 and B95-8 strains of Epstein-Barr virus (EBV) were cytocidal for EBV-carrier human cell lines, as revealed by a colony inhibition procedure. The cytocidal activity was proportional to virus dose added. The cell killing was neutralized by anti-EBV antibody-positive but not -negative human sera. When the relative sensitivity to ultraviolet light of EBV activities was examined, the cytocidal actitivy was much more resistant than the viral infectivity as assayed by early antigen-forming activity (P3HR-1 virus) or leukocyte-transforming activity (B95-8 virus), but it closely paralleled the ability to adsorb to cells."} {"id": "PMID:176119", "title": "Characteristics of three strains of feline fibrosarcoma virus grown in cat and marmoset monkey cells.", "content": "Two strains of feline fibrosarcoma virus (ST-FeSV and GA-FeSV) were found to induce tumors in cats and marmosets, and to transform feline and marmoset cells in vitro after primary inoculation. A third strain (SM-FeSV) failed to induce tumors or transform marmoset cells after primary inoculation; however, when SM-FeSV-injected marmoset cultures were passed 26 times in vitro, the cell cultures released infectious virus which transformed marmoset fibroblasts but still failed to induce tumors in marmosets. ST-FeSV induced mainly round-cell type transformation (r foci), GA-FeSV induced predominantly mixed round-fusiform cell type transformation (fr foci), and SM-FeSV induced r and fr type foci with a higher proportion of fusiform cells in the fr foci than seen with GA-FeSV. Transforming virus was obtained from r or mixed r/fr foci of ST-FeSV but not from fr foci; heat treatment changed the virus from producing almost exclusively r type foci to inducing an increased number of fr foci. Passage of FeSV in cat cells yielded viruses with a higher ratio of infectivity for feline vs marmoset cells, while passage of FeSV in marmoset cells yielded virus with a relatively higher infectivity ratio for marmoset cells; the three strains differed in the degree of change in the infectivity ratio. Despite the alteration of host range of SM-FeSV propagated in marmoset fibroblasts, the virus retained feline P-30 antigen by CF and FA assays. Neutralization tests did not indicate but also did not exclude an alteration of the surface antigens of ST-FeSV or SM-FeSV propagated in marmoset fibroblasts. The alteration of the relative infectivity of FeSV during passage in marmoset cells may be due to: (1) the selection of a variant present in the original heterogenous uncloned population; (2) mutation; or (3) recombination with some marmoset genetic material, possibly an as yet unidentified endogenous marmoset virus.", "contents": "Characteristics of three strains of feline fibrosarcoma virus grown in cat and marmoset monkey cells. Two strains of feline fibrosarcoma virus (ST-FeSV and GA-FeSV) were found to induce tumors in cats and marmosets, and to transform feline and marmoset cells in vitro after primary inoculation. A third strain (SM-FeSV) failed to induce tumors or transform marmoset cells after primary inoculation; however, when SM-FeSV-injected marmoset cultures were passed 26 times in vitro, the cell cultures released infectious virus which transformed marmoset fibroblasts but still failed to induce tumors in marmosets. ST-FeSV induced mainly round-cell type transformation (r foci), GA-FeSV induced predominantly mixed round-fusiform cell type transformation (fr foci), and SM-FeSV induced r and fr type foci with a higher proportion of fusiform cells in the fr foci than seen with GA-FeSV. Transforming virus was obtained from r or mixed r/fr foci of ST-FeSV but not from fr foci; heat treatment changed the virus from producing almost exclusively r type foci to inducing an increased number of fr foci. Passage of FeSV in cat cells yielded viruses with a higher ratio of infectivity for feline vs marmoset cells, while passage of FeSV in marmoset cells yielded virus with a relatively higher infectivity ratio for marmoset cells; the three strains differed in the degree of change in the infectivity ratio. Despite the alteration of host range of SM-FeSV propagated in marmoset fibroblasts, the virus retained feline P-30 antigen by CF and FA assays. Neutralization tests did not indicate but also did not exclude an alteration of the surface antigens of ST-FeSV or SM-FeSV propagated in marmoset fibroblasts. The alteration of the relative infectivity of FeSV during passage in marmoset cells may be due to: (1) the selection of a variant present in the original heterogenous uncloned population; (2) mutation; or (3) recombination with some marmoset genetic material, possibly an as yet unidentified endogenous marmoset virus."} {"id": "PMID:176120", "title": "A radiometric method for predicting effectiveness of chemotherapeutic agents in murine leprosy.", "content": "A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M. lepraemurium. The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C. Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin. The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness. The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M. lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible. Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M. leprae in vitro.", "contents": "A radiometric method for predicting effectiveness of chemotherapeutic agents in murine leprosy. A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M. lepraemurium. The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C. Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin. The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness. The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M. lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible. Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M. leprae in vitro."} {"id": "PMID:176129", "title": "Immune host response to corneal grafts sensitized to herpes simplex virus.", "content": "Experiments were performed to study the fate of corneal grafts sensitized to herpes antigens when grafted to HSV-sensitized hosts. Nonsensitized grafts in systemically sensitized hosts remained clear, whereas all locally sensitized grafts in systemically sensitized hosts became opaque within ten days. The stroma showed severe lymphocytic and plasma cell infiltration and neovascularization. One-half of the corneas from systemically sensitized hosts grafted to eyes previously infected opacified in an accelerated manner. Round cells were found in the stroma and endothelium. The histological reaction in both groups was similar to that found in the immune graft reaction even though the clinical picture was not typical (peripheral and progressive edema with a rejection line). The accelerated reaction was probably related to the presence of virus antigens in graft stroma and subepithelial areas of the graft. The significance of HSV-sensitized donor tissue grafted onto HSV-sensitized hosts is discussed because of its possible implication in tissue transplantation.", "contents": "Immune host response to corneal grafts sensitized to herpes simplex virus. Experiments were performed to study the fate of corneal grafts sensitized to herpes antigens when grafted to HSV-sensitized hosts. Nonsensitized grafts in systemically sensitized hosts remained clear, whereas all locally sensitized grafts in systemically sensitized hosts became opaque within ten days. The stroma showed severe lymphocytic and plasma cell infiltration and neovascularization. One-half of the corneas from systemically sensitized hosts grafted to eyes previously infected opacified in an accelerated manner. Round cells were found in the stroma and endothelium. The histological reaction in both groups was similar to that found in the immune graft reaction even though the clinical picture was not typical (peripheral and progressive edema with a rejection line). The accelerated reaction was probably related to the presence of virus antigens in graft stroma and subepithelial areas of the graft. The significance of HSV-sensitized donor tissue grafted onto HSV-sensitized hosts is discussed because of its possible implication in tissue transplantation."} {"id": "PMID:176130", "title": "Immunofluorescent detection of adenovirus antigen in epidemic keratoconjunctivitis.", "content": "An immunofluorescent technique was used to demonstrate soluble adenoviral antigens in epithelial cells on conjunctival scrapings of patients with epidemic keratoconjunctivitis (EKC). Conjunctival scrapings for immunofluorescence and viral isolation studies were performed on 79 patients suspected of having EKC or other acute follicular or papillary conjunctivitides. Of 41 patients with clinical findings consistent with a diagnosis of EKC and three patients with pharyngoconjunctional fever, 43 were positive by immunofluorescence. All 39 patients with adenovirus isolation had positive immunofluorescence studies. The five remaining cases had other documented evidence of EKC. No false-positive responses were encountered in relation to the clinical diagnoses. The fluorescent staining was predominantly found in the cytoplasm. Speckled nuclear fluorescence was also noted. The cytoplasmic fluorescence is compatible with the adenovirus cellular replication cycle. The immunofluorescent technique was found to be a reliable, sensitive, specific, and rapid diagnostic technique for detection of group-reaction adenoviral antigens in conjunctival scrapings.", "contents": "Immunofluorescent detection of adenovirus antigen in epidemic keratoconjunctivitis. An immunofluorescent technique was used to demonstrate soluble adenoviral antigens in epithelial cells on conjunctival scrapings of patients with epidemic keratoconjunctivitis (EKC). Conjunctival scrapings for immunofluorescence and viral isolation studies were performed on 79 patients suspected of having EKC or other acute follicular or papillary conjunctivitides. Of 41 patients with clinical findings consistent with a diagnosis of EKC and three patients with pharyngoconjunctional fever, 43 were positive by immunofluorescence. All 39 patients with adenovirus isolation had positive immunofluorescence studies. The five remaining cases had other documented evidence of EKC. No false-positive responses were encountered in relation to the clinical diagnoses. The fluorescent staining was predominantly found in the cytoplasm. Speckled nuclear fluorescence was also noted. The cytoplasmic fluorescence is compatible with the adenovirus cellular replication cycle. The immunofluorescent technique was found to be a reliable, sensitive, specific, and rapid diagnostic technique for detection of group-reaction adenoviral antigens in conjunctival scrapings."} {"id": "PMID:176138", "title": "High-pressure liquid chromatographic determination of vitamin D3 in resins, oils, dry concentrates, and dry concentrates containing vitamin A.", "content": "A high-pressur liquid chromatographic (HPLC) procedure has been developed for the determination of vitamin D3 in resins, oils, dry concentrates, and dry concentrates containing vitamin A. Specificity of the method for vitamin D3 in the presence of isomers and other related constituents was shown by ultimate recovery of the vitamin D3 and the individual constituents and their characterization by other methods such as ultraviolet spectrophotometry. Precision and accuracy are within 2%, and as many as 20 determinations may be completed in a working day. Excellent agreement with the official AOAC biological assay was found. A comparison of the response of isomers of vitamin D3 by the HPLC method vs. other instrumental and chemical procedures shows HPLC to be the most specific method for determining the bioactive isomers.", "contents": "High-pressure liquid chromatographic determination of vitamin D3 in resins, oils, dry concentrates, and dry concentrates containing vitamin A. A high-pressur liquid chromatographic (HPLC) procedure has been developed for the determination of vitamin D3 in resins, oils, dry concentrates, and dry concentrates containing vitamin A. Specificity of the method for vitamin D3 in the presence of isomers and other related constituents was shown by ultimate recovery of the vitamin D3 and the individual constituents and their characterization by other methods such as ultraviolet spectrophotometry. Precision and accuracy are within 2%, and as many as 20 determinations may be completed in a working day. Excellent agreement with the official AOAC biological assay was found. A comparison of the response of isomers of vitamin D3 by the HPLC method vs. other instrumental and chemical procedures shows HPLC to be the most specific method for determining the bioactive isomers."} {"id": "PMID:176140", "title": "Cyclic guanosine 3',5'-monophosphate in the dimorphic fungus Mucor racemosus.", "content": "The dimorphic fungus Mucor racemosus was found to contain the cyclic nucleotide guanosine 3',5'-monophosphate (cGMP). Approximately equivalent amounts of the compound were found in ungerminated spores, yeastlike cells, and mycelia. Germinating spores contained severalfold higher amounts of cGMP than the other cell forms. cGMP levels did not change significantly during the morphogenetic conversion of yeast to mycelia. Added exogenous cGMP or the dibutyryl derivative did not influence cell morphology in any way and did not alter the effect that cyclic adenosine 3',5'-monophosphate has upon cell morphology.", "contents": "Cyclic guanosine 3',5'-monophosphate in the dimorphic fungus Mucor racemosus. The dimorphic fungus Mucor racemosus was found to contain the cyclic nucleotide guanosine 3',5'-monophosphate (cGMP). Approximately equivalent amounts of the compound were found in ungerminated spores, yeastlike cells, and mycelia. Germinating spores contained severalfold higher amounts of cGMP than the other cell forms. cGMP levels did not change significantly during the morphogenetic conversion of yeast to mycelia. Added exogenous cGMP or the dibutyryl derivative did not influence cell morphology in any way and did not alter the effect that cyclic adenosine 3',5'-monophosphate has upon cell morphology."} {"id": "PMID:176141", "title": "Control of transformation competence in Azotobacter vinelandii by nitrogen catabolite derepression.", "content": "Azotobacter vinelandii (ATCC 12837) became competent to be transformed by exogenous deoxyribonucleic acid towards the end of exponential growth. Competence in wild-type and nitrogenase auxotrophic (nif-) strains was repressed by the addition of ammonium salts or urea to the transformation medium. Transformation of wild-type cells and nif- strains was optimal on nitrogen-free or nitrogen-limiting medium, respectively. Transformation of wild-type cells also was enhanced when the transformation medium had low molydbate content. During the development of competence, nitrogen was growth limiting, whereas carbon (glucose) was in excess. Carbon source shift-down was not effective in inducing competence. Shifting glucose-grown wild-type cells to medium containing 0.2% beta-hydroxybutyrate initiated encystment and also induced competence. The addition of glucose to this medium blocked encystment and early competence induction and reduced the transformation frequency to the basal level. Cyclic adenosine 3',5'-monophosphate induced competence in wild-type nitrogen-fixing cells and increased the transformation frequency 1,000-fold over the basal level. Exogenous cyclic adenosine 3',5'-monophosphate however, did not reverse nitrogen repression of competence in ammonia-grown wild-type or nif- strains.", "contents": "Control of transformation competence in Azotobacter vinelandii by nitrogen catabolite derepression. Azotobacter vinelandii (ATCC 12837) became competent to be transformed by exogenous deoxyribonucleic acid towards the end of exponential growth. Competence in wild-type and nitrogenase auxotrophic (nif-) strains was repressed by the addition of ammonium salts or urea to the transformation medium. Transformation of wild-type cells and nif- strains was optimal on nitrogen-free or nitrogen-limiting medium, respectively. Transformation of wild-type cells also was enhanced when the transformation medium had low molydbate content. During the development of competence, nitrogen was growth limiting, whereas carbon (glucose) was in excess. Carbon source shift-down was not effective in inducing competence. Shifting glucose-grown wild-type cells to medium containing 0.2% beta-hydroxybutyrate initiated encystment and also induced competence. The addition of glucose to this medium blocked encystment and early competence induction and reduced the transformation frequency to the basal level. Cyclic adenosine 3',5'-monophosphate induced competence in wild-type nitrogen-fixing cells and increased the transformation frequency 1,000-fold over the basal level. Exogenous cyclic adenosine 3',5'-monophosphate however, did not reverse nitrogen repression of competence in ammonia-grown wild-type or nif- strains."} {"id": "PMID:176142", "title": "Transcriptional and post-transcriptional control of beta-galactosidase synthesis.", "content": "lac messenger ribonucleic acid synthesis is dissociated from its translation in certain lac operon mutants. More beta-galactosidase messenger ribonucleic acid (as determined by hybridization) is made in fully induced lacOc mutants and in trp-lac fusions than is eventually translated into enzyme. Consequently, beta-galactosidase synthesis may be post-transcriptionally controlled under these conditions.", "contents": "Transcriptional and post-transcriptional control of beta-galactosidase synthesis. lac messenger ribonucleic acid synthesis is dissociated from its translation in certain lac operon mutants. More beta-galactosidase messenger ribonucleic acid (as determined by hybridization) is made in fully induced lacOc mutants and in trp-lac fusions than is eventually translated into enzyme. Consequently, beta-galactosidase synthesis may be post-transcriptionally controlled under these conditions."} {"id": "PMID:176143", "title": "Cytochrome spectrum of an obligate anaerobe, Eubacterium lentum.", "content": "An obligately anaerobic bacterium, Eubacterium lentum, was shown to contain cytochromes a, b, and c and a carbon monoxide-binding pigment. Extracts of cells grown with hemin gave a typical absorption spectrum for cytochrome c with maxima at 424, 525, and 553 nm. Extracts from cells grown in the absence of hemin also had an absorption peak corresponding to cytochrome b (562 nm) in their reduced versus oxidized spectrum. Extraction of hemes and formation of pyridine hemochromes allowed quantitation of protoheme IX and heme c. Large amounts of cytochrome c masked the presence of cytochrome b in cells grown in medium containing hemin. When cells were grown in the presence of 50 mM nitrate, cytochrome A (606 nm) was detected. In anaerobic extracts of cells grown either with or without nitrate, cytochromes b and c were reduced by formate and oxidized by NO3. Cytochrome a appeared to be partially oxidized by NO3 and completely oxidized by air.", "contents": "Cytochrome spectrum of an obligate anaerobe, Eubacterium lentum. An obligately anaerobic bacterium, Eubacterium lentum, was shown to contain cytochromes a, b, and c and a carbon monoxide-binding pigment. Extracts of cells grown with hemin gave a typical absorption spectrum for cytochrome c with maxima at 424, 525, and 553 nm. Extracts from cells grown in the absence of hemin also had an absorption peak corresponding to cytochrome b (562 nm) in their reduced versus oxidized spectrum. Extraction of hemes and formation of pyridine hemochromes allowed quantitation of protoheme IX and heme c. Large amounts of cytochrome c masked the presence of cytochrome b in cells grown in medium containing hemin. When cells were grown in the presence of 50 mM nitrate, cytochrome A (606 nm) was detected. In anaerobic extracts of cells grown either with or without nitrate, cytochromes b and c were reduced by formate and oxidized by NO3. Cytochrome a appeared to be partially oxidized by NO3 and completely oxidized by air."} {"id": "PMID:176144", "title": "Binding of (125I)iodohydroxybenzylpindolol to putative beta-adrenergic receptors of rat glioma cells and other cell clones.", "content": "[125I]Iodohydroxybenzylpindolol, an extremely potent beta-adrenergic antagonist, has been purified to theoretical specific activity (2200 Ci/mmol) and used as a ligand to characterize the beta-adrenergic receptors of cultured rat glioma cells and other cultured cell clones. Appropriate receptor sites were identified by stereoselective competition for binding by a number of adrenergic agonists and antagonists, by correlation between the potency of these compounds to inhibit binding and to affect adenylate cyclase activity, and by correlation of binding with the presence or absence of response to catecholamines (stimulation of adenylate cyclase) in various cell clones. In equilibrium experiments, the dissociation constant for binding of the iodinated ligand to the beta-adrenergic receptor of a clone of rat glioma cells (C6TG1A) was 250 pM; the corresponding value for a clone of human fibroblasts (VA2) was 15 pM. For C6TG1A, KD was verified by analysis of the kinetics of binding: k1 = 10(8) 1/mol/min: k-1 = 0.017/min. This rate of dissociation of ligand from the receptor was also established by study of the rate of activation of adenylate cyclase by isoproterenol after prior equilibration with iodohydroxybenzylpindolol. For VA2 cells, where affinity was higher, the rate of reversal of binding was only 0.0035/min. C6TG1A contained approximately 4000 receptor sites/cell (75 fmol/mg of protein), and these sites appeared to be coupled to adenylate cyclase in a stoichiometric manner. A second site with equal affinity for iodohydroxybenzylpindolol (KD = 250 pM) was also identified in C6TG1A by both kinetic analysis and equilibrium binding studies. While most compounds that interacted with the beta-adrenergic receptor also influenced binding to the second site, the latter did not distinguish between stereoisomers of propranolol, and its affinity for the other compounds tested was poorer.", "contents": "Binding of (125I)iodohydroxybenzylpindolol to putative beta-adrenergic receptors of rat glioma cells and other cell clones. [125I]Iodohydroxybenzylpindolol, an extremely potent beta-adrenergic antagonist, has been purified to theoretical specific activity (2200 Ci/mmol) and used as a ligand to characterize the beta-adrenergic receptors of cultured rat glioma cells and other cultured cell clones. Appropriate receptor sites were identified by stereoselective competition for binding by a number of adrenergic agonists and antagonists, by correlation between the potency of these compounds to inhibit binding and to affect adenylate cyclase activity, and by correlation of binding with the presence or absence of response to catecholamines (stimulation of adenylate cyclase) in various cell clones. In equilibrium experiments, the dissociation constant for binding of the iodinated ligand to the beta-adrenergic receptor of a clone of rat glioma cells (C6TG1A) was 250 pM; the corresponding value for a clone of human fibroblasts (VA2) was 15 pM. For C6TG1A, KD was verified by analysis of the kinetics of binding: k1 = 10(8) 1/mol/min: k-1 = 0.017/min. This rate of dissociation of ligand from the receptor was also established by study of the rate of activation of adenylate cyclase by isoproterenol after prior equilibration with iodohydroxybenzylpindolol. For VA2 cells, where affinity was higher, the rate of reversal of binding was only 0.0035/min. C6TG1A contained approximately 4000 receptor sites/cell (75 fmol/mg of protein), and these sites appeared to be coupled to adenylate cyclase in a stoichiometric manner. A second site with equal affinity for iodohydroxybenzylpindolol (KD = 250 pM) was also identified in C6TG1A by both kinetic analysis and equilibrium binding studies. While most compounds that interacted with the beta-adrenergic receptor also influenced binding to the second site, the latter did not distinguish between stereoisomers of propranolol, and its affinity for the other compounds tested was poorer."} {"id": "PMID:176145", "title": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. I. Activation by phospholipids and fatty acids.", "content": "The activation of C55-isoprenoid alcohol phosphokinase by a variety of lipids has been investigated. A number of amphipathic lipids can serve as effective kinase activators. Both the nature of the polar and nonpolar groups are important, but kinase activation does not depend on any particular chemical structure or charge on the lipid. The structure of those lipids which are most effective, as well as an analysis of their temperature profiles, suggests that bulk physical properties are significant. Lipids which provide a hydrated, loosely packed, highly fluid environment are often effective activators.", "contents": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. I. Activation by phospholipids and fatty acids. The activation of C55-isoprenoid alcohol phosphokinase by a variety of lipids has been investigated. A number of amphipathic lipids can serve as effective kinase activators. Both the nature of the polar and nonpolar groups are important, but kinase activation does not depend on any particular chemical structure or charge on the lipid. The structure of those lipids which are most effective, as well as an analysis of their temperature profiles, suggests that bulk physical properties are significant. Lipids which provide a hydrated, loosely packed, highly fluid environment are often effective activators."} {"id": "PMID:176146", "title": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. II. Biophysical studies.", "content": "Physicochemical techniques were used to investigate the activation of C55-isoprenoid alcohol phosphokinase by synthetic lecithins. Complexes of the enzyme with phospholipids were prepared using a method employing sodium dodecyl sulfate as a protein-solubilizing agent. Circular dichorism and the intrinsic fluorescence of the kinase were used as optical probes of protein conformation with these complexes. No evidence for a major lipid-dependent conformational change in the protein was observed when these complexes were studied under conditions where the lipid mesomorphic transitions occurred. EPR studies of mixtures of synthetic lecithins and the C55-isoprenoid alcohol indicated a correlation between kinase activity and the rotational diffusion rate within the hydrophobic phase. It is concluded that the lipid physical state probably does not affect the enzyme activity by altering the protein conformation but more likely does so by affecting the motion of the molecular participants in the reaction.", "contents": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. II. Biophysical studies. Physicochemical techniques were used to investigate the activation of C55-isoprenoid alcohol phosphokinase by synthetic lecithins. Complexes of the enzyme with phospholipids were prepared using a method employing sodium dodecyl sulfate as a protein-solubilizing agent. Circular dichorism and the intrinsic fluorescence of the kinase were used as optical probes of protein conformation with these complexes. No evidence for a major lipid-dependent conformational change in the protein was observed when these complexes were studied under conditions where the lipid mesomorphic transitions occurred. EPR studies of mixtures of synthetic lecithins and the C55-isoprenoid alcohol indicated a correlation between kinase activity and the rotational diffusion rate within the hydrophobic phase. It is concluded that the lipid physical state probably does not affect the enzyme activity by altering the protein conformation but more likely does so by affecting the motion of the molecular participants in the reaction."} {"id": "PMID:176147", "title": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. III. Activation by detergents.", "content": "The activation of kinase by neutral detergents has been examined. Of those detergents tested, only those with short chain and unsaturated chain hydrophobes were successful activators at 25 degrees. In addition to these structural requirements, a dependence upon hydrophilic-lipophilic balance number was observed when mixing hydrophobic and hydrophilic detergents. Most pairs tested showed an optimal hydrophilic-lipophilic balance number for kinase activation in the hydrophobic range of 6 to 9. Thus, there appears to be both a structural and a relative hydrophobic requirement for activation, and hydrophilic-lipophilic balance number may be a measure of the physical properties of the lipid required for activation.", "contents": "Activation of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. III. Activation by detergents. The activation of kinase by neutral detergents has been examined. Of those detergents tested, only those with short chain and unsaturated chain hydrophobes were successful activators at 25 degrees. In addition to these structural requirements, a dependence upon hydrophilic-lipophilic balance number was observed when mixing hydrophobic and hydrophilic detergents. Most pairs tested showed an optimal hydrophilic-lipophilic balance number for kinase activation in the hydrophobic range of 6 to 9. Thus, there appears to be both a structural and a relative hydrophobic requirement for activation, and hydrophilic-lipophilic balance number may be a measure of the physical properties of the lipid required for activation."} {"id": "PMID:176148", "title": "Protein asymmetry in the inner membrane of rat liver mitochondria.", "content": "At least three groups of polypeptides of the inner membrane of rat liver mitochondria have been shown to be exposed to the exterior surface by several techniques: lactoperoxidase-catalyzed iodination of mitochondria and inner membrane/matrix vesicles (mitoplasts), reaction of mitochondria and mitoplasts with the membrane-impermeable diazonium salt of sulfanilic acid, and controlled proteolysis of mitoplasts. These classes of proteins, separated by dodecyl sulfate gel electrophoresis, have polypeptide molecular weights of 73,000, 31,000, and 26,000. In addition, four other groups have been shown to be exposed to the exterior surface by at least one of these techniques: these components have polypeptide molecular weights of 130,000, 87,000, 16,000, and 10,500. A class of proteins, which makes up 50 to 60% of the total mitochondrial protein and which can be easily extracted from mitoplasts by freeze-thaw fractionation or other procedures designed to separate \"matrix\" protein from \"membrane\" protein, is shown not to be exposed to the outer surface of the inner membrane by these techniques. This class of proteins contains polypeptides of various molecular weights and includes the major 165,000 molecular weight polypeptide, identified with carbamyl phosphate synthetase.", "contents": "Protein asymmetry in the inner membrane of rat liver mitochondria. At least three groups of polypeptides of the inner membrane of rat liver mitochondria have been shown to be exposed to the exterior surface by several techniques: lactoperoxidase-catalyzed iodination of mitochondria and inner membrane/matrix vesicles (mitoplasts), reaction of mitochondria and mitoplasts with the membrane-impermeable diazonium salt of sulfanilic acid, and controlled proteolysis of mitoplasts. These classes of proteins, separated by dodecyl sulfate gel electrophoresis, have polypeptide molecular weights of 73,000, 31,000, and 26,000. In addition, four other groups have been shown to be exposed to the exterior surface by at least one of these techniques: these components have polypeptide molecular weights of 130,000, 87,000, 16,000, and 10,500. A class of proteins, which makes up 50 to 60% of the total mitochondrial protein and which can be easily extracted from mitoplasts by freeze-thaw fractionation or other procedures designed to separate \"matrix\" protein from \"membrane\" protein, is shown not to be exposed to the outer surface of the inner membrane by these techniques. This class of proteins contains polypeptides of various molecular weights and includes the major 165,000 molecular weight polypeptide, identified with carbamyl phosphate synthetase."} {"id": "PMID:176149", "title": "Regulation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria.", "content": "The mechanism by which fatty acid addition leads to the inactivation of pyruvate dehydrogenase in intact rat liver mitochondria was investigated. In all cases the fatty acid octanoate was added to mitochondria oxidizing succinate. Addition of fatty acid caused an inactivation of pyruvate dehydrogenase in mitochondria incubated under State 3 conditions (glucose plus hexokinase), in uncoupled, oligomycin-treated mitochondria, and in rotenone-menadione-treated mitochondria, but not in uncoupled mitochondria or in mitochondria incubated under State 4 conditions. A number of metabolic conditions were found in which pyruvate dehydrogenase was inactivated concomitant with an elevation in the ATP/ADP ratio. This is consistent with the inverse relationship between the ATP/ADP ratio and the pyruvate dehydrogenase activity proposed by various laboratories. However, in several other metabolic conditions pyruvate dehydrogenase was inactivated while the ATP/ADP ratio either was unchanged or even decreased. This observation implies that there are likely other regulatory factors involved in the fatty acid-mediated inactivation of pyruvate dehydrogenase. Incubation conditions in State 3 were found in which the ATP/ADP and the acetyl-CoA/CoASH ratios remained constant and the pyruvate dehydrogenase activity was correlated inversely with the NADH/NAD+ ratio. Other State 3 conditions were found in which the ATP/ADP and the NADH/NAD+ ratios remained constant while the pyruvate dehydrogenase activity was correlated inversely with the acetyl-CoA/CoASH ratio. Further evidence supporting these experiments with intact mitochondria was the observation that the pyruvate dehydrogenase kinase activity of a mitochondrial extract was stimulated strongly by acetyl-CoA and was inhibited by NAD+ and CoASH. In contrast to acetyl-CoA, octanoyl-CoA inhibited the kinase activity. These results indicate that the inactivation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria may be mediated through effects of the NADH/NAD+ ratio and the acetyl-CoA/CoASH ratio on the interconversion of the active and inactive forms of the enzyme complex catalyzed by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase.", "contents": "Regulation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria. The mechanism by which fatty acid addition leads to the inactivation of pyruvate dehydrogenase in intact rat liver mitochondria was investigated. In all cases the fatty acid octanoate was added to mitochondria oxidizing succinate. Addition of fatty acid caused an inactivation of pyruvate dehydrogenase in mitochondria incubated under State 3 conditions (glucose plus hexokinase), in uncoupled, oligomycin-treated mitochondria, and in rotenone-menadione-treated mitochondria, but not in uncoupled mitochondria or in mitochondria incubated under State 4 conditions. A number of metabolic conditions were found in which pyruvate dehydrogenase was inactivated concomitant with an elevation in the ATP/ADP ratio. This is consistent with the inverse relationship between the ATP/ADP ratio and the pyruvate dehydrogenase activity proposed by various laboratories. However, in several other metabolic conditions pyruvate dehydrogenase was inactivated while the ATP/ADP ratio either was unchanged or even decreased. This observation implies that there are likely other regulatory factors involved in the fatty acid-mediated inactivation of pyruvate dehydrogenase. Incubation conditions in State 3 were found in which the ATP/ADP and the acetyl-CoA/CoASH ratios remained constant and the pyruvate dehydrogenase activity was correlated inversely with the NADH/NAD+ ratio. Other State 3 conditions were found in which the ATP/ADP and the NADH/NAD+ ratios remained constant while the pyruvate dehydrogenase activity was correlated inversely with the acetyl-CoA/CoASH ratio. Further evidence supporting these experiments with intact mitochondria was the observation that the pyruvate dehydrogenase kinase activity of a mitochondrial extract was stimulated strongly by acetyl-CoA and was inhibited by NAD+ and CoASH. In contrast to acetyl-CoA, octanoyl-CoA inhibited the kinase activity. These results indicate that the inactivation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria may be mediated through effects of the NADH/NAD+ ratio and the acetyl-CoA/CoASH ratio on the interconversion of the active and inactive forms of the enzyme complex catalyzed by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase."} {"id": "PMID:176150", "title": "Studies on the chlorinating activity of myeloperoxidase.", "content": "Two methods were utilized to demonstrate the peroxidation of chloride ion to a free species (HOCl or Cl2) by myeloperoxidase. The peroxidase caused the volatilization of radioactivity from soultions containing hydrogen peroxide and [36Cl]NaCl, and catalyzed the formation of HOCl when solutions contianing these components were passed through a Millipore filter to which the peroxidase was adsorbed. In this flow system, 90 mug of canine myeloperoxidase generated 80 muM HOCl in the presence of 200 muM H2O2 at a rate corresponding to a turnover of 100 min-1. Under these conditions, o-tolidine, whose oxidation can be coupled to Cl- peroxidation in free solution, did not accelerate turnover. In contrast to chloroperoxidase and horseradish peroxidase, myeloperoxidase does not utilize chlorite for chlorination reactions. This oxidant inactivates the enzyme. At low pH, chloride ion suppresses the oxidation of myeloperoxidase (to the stable compound II) by both hydrogen peroxide and hypochlorite. Acceptor chlorination is therefore not a rate-controlling reaction in the myeloperoxidase mechanism, and the potential of the functional peroxidase couple is higher than the HOCl/Cl- couple under chlorinating conditions. The product-forming step may be a reverse of compound I formation at the expense of HOCl, rather than the chlorination of Cl- by a chloroperoxidase-like chlorinating intermediate.", "contents": "Studies on the chlorinating activity of myeloperoxidase. Two methods were utilized to demonstrate the peroxidation of chloride ion to a free species (HOCl or Cl2) by myeloperoxidase. The peroxidase caused the volatilization of radioactivity from soultions containing hydrogen peroxide and [36Cl]NaCl, and catalyzed the formation of HOCl when solutions contianing these components were passed through a Millipore filter to which the peroxidase was adsorbed. In this flow system, 90 mug of canine myeloperoxidase generated 80 muM HOCl in the presence of 200 muM H2O2 at a rate corresponding to a turnover of 100 min-1. Under these conditions, o-tolidine, whose oxidation can be coupled to Cl- peroxidation in free solution, did not accelerate turnover. In contrast to chloroperoxidase and horseradish peroxidase, myeloperoxidase does not utilize chlorite for chlorination reactions. This oxidant inactivates the enzyme. At low pH, chloride ion suppresses the oxidation of myeloperoxidase (to the stable compound II) by both hydrogen peroxide and hypochlorite. Acceptor chlorination is therefore not a rate-controlling reaction in the myeloperoxidase mechanism, and the potential of the functional peroxidase couple is higher than the HOCl/Cl- couple under chlorinating conditions. The product-forming step may be a reverse of compound I formation at the expense of HOCl, rather than the chlorination of Cl- by a chloroperoxidase-like chlorinating intermediate."} {"id": "PMID:176151", "title": "Role of cortisol on the glycogenolytic effect of glucagon and on the glycogenic response to insulin in fetal hepatocyte culture.", "content": "The effects of insulin and glucagon on glycogen metabolism were studied in cultured fetal hepatocytes transplanted from 15-day-old fetuses. The effects of these hormones were examined just after transplantation, when the cells contained only minute amounts of glycogen, and during the 3 to 4 day culture period, when the hepatocytes were exposed to 10 muM cortisol and actively accumulated glycogen. At all stages of the culture, glucagon addition (10 nM) was followed by a rapid depletion of labeled glycogen, previously synthesized during a pulse labeling with [14C]glucose: this effect was mimicked by N6, O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) (0.3 to 1 nM). Such a glycogenolytic effect of glucagon was observed even 6 hours after transplantation, i.e. at a time when cortisol was not present. In addition, glucagon clearly induced cyclic adenosine 3':5'-monosphosphate (cyclic AMP) accumulation in cells grown for 18 hours in the absence of cortisol. With cells grown for 3 days in the presence of cortisol, glucagon-dependent glycogenolysis was also obtained when cortisol was removed from the medium 20 hours before hormone addition. Thus the presence of cortisol is not necessary either to maintain a response to glucagon or for the onset of the glycogenolytic effect of glucagon. Insulin addition (10 nM) stimulated [14C]glucose incorporation into glycogen at all stages of the culture when grown in the presence of cortisol; no glycogenic response to insulin was observed 6 hours after transplantation where cortisol was not previously introduced. In addition, if the hepatocytes were grown in the presence of insulin alone (i.e. in the absence of cortisol) no significant storage of glycogen occurred. Maximal storage (or labeling) of glycogen was observed when hepatocytes were grown in the presence of both cortisol and insulin. The presence of cortisol was therefore necessary for the expression of the glycogenic effect of insulin. These data show that marked difference exist between the onset of developmental responses towards glucagon and insulin. The glucagon-dependent regulatory pathway should be present very early in fetal development and should not depend on cortisol. On the contrary, the onset of the insulin-dependent regulatory pathway seems to be induced during culture, and it is likely that this is caused by cortisol.", "contents": "Role of cortisol on the glycogenolytic effect of glucagon and on the glycogenic response to insulin in fetal hepatocyte culture. The effects of insulin and glucagon on glycogen metabolism were studied in cultured fetal hepatocytes transplanted from 15-day-old fetuses. The effects of these hormones were examined just after transplantation, when the cells contained only minute amounts of glycogen, and during the 3 to 4 day culture period, when the hepatocytes were exposed to 10 muM cortisol and actively accumulated glycogen. At all stages of the culture, glucagon addition (10 nM) was followed by a rapid depletion of labeled glycogen, previously synthesized during a pulse labeling with [14C]glucose: this effect was mimicked by N6, O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) (0.3 to 1 nM). Such a glycogenolytic effect of glucagon was observed even 6 hours after transplantation, i.e. at a time when cortisol was not present. In addition, glucagon clearly induced cyclic adenosine 3':5'-monosphosphate (cyclic AMP) accumulation in cells grown for 18 hours in the absence of cortisol. With cells grown for 3 days in the presence of cortisol, glucagon-dependent glycogenolysis was also obtained when cortisol was removed from the medium 20 hours before hormone addition. Thus the presence of cortisol is not necessary either to maintain a response to glucagon or for the onset of the glycogenolytic effect of glucagon. Insulin addition (10 nM) stimulated [14C]glucose incorporation into glycogen at all stages of the culture when grown in the presence of cortisol; no glycogenic response to insulin was observed 6 hours after transplantation where cortisol was not previously introduced. In addition, if the hepatocytes were grown in the presence of insulin alone (i.e. in the absence of cortisol) no significant storage of glycogen occurred. Maximal storage (or labeling) of glycogen was observed when hepatocytes were grown in the presence of both cortisol and insulin. The presence of cortisol was therefore necessary for the expression of the glycogenic effect of insulin. These data show that marked difference exist between the onset of developmental responses towards glucagon and insulin. The glucagon-dependent regulatory pathway should be present very early in fetal development and should not depend on cortisol. On the contrary, the onset of the insulin-dependent regulatory pathway seems to be induced during culture, and it is likely that this is caused by cortisol."} {"id": "PMID:176152", "title": "Tissue-specific chromosomal non-histone protein interactions with DNA.", "content": "A group of chromosomal non-histone proteins with affinity for DNA (NP) was isolated from rat liver and Novikoff hepatoma. This fraction, which represents less than 5% of the total chromatin protein content, binds preferentially to unique, double-stranded sequences of fractionated homologous DNA. The interactions are strong at low ionic strength (Km = 6.7 X 10(-9) M) and decrease with rising salt concentration. Complexes of the NP protein fraction with homologous DNA are immunologically tissue-specific. As determined by microcomplement fixation, the NP proteins in Novikoff hepatoma are associated with the transcriptionally active, diffuse fraction of chromatin.", "contents": "Tissue-specific chromosomal non-histone protein interactions with DNA. A group of chromosomal non-histone proteins with affinity for DNA (NP) was isolated from rat liver and Novikoff hepatoma. This fraction, which represents less than 5% of the total chromatin protein content, binds preferentially to unique, double-stranded sequences of fractionated homologous DNA. The interactions are strong at low ionic strength (Km = 6.7 X 10(-9) M) and decrease with rising salt concentration. Complexes of the NP protein fraction with homologous DNA are immunologically tissue-specific. As determined by microcomplement fixation, the NP proteins in Novikoff hepatoma are associated with the transcriptionally active, diffuse fraction of chromatin."} {"id": "PMID:176153", "title": "Comparison of mode of activation of guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases from silkworm.", "content": "Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) partially purified from silkworm pupae was selectively activated by cyclic GMP at lower concentrations. Nevertheless, the enzyme seemed to differ from adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) with respect to the mode of response to cyclic nucleotides. The catalytic activity and cyclic GMP-binding activity were not dissociated by cyclic GMP in a manner similar to that described for protein kinase A. The enzyme was not inhibited by regulatory subunit of protein kinase A nor by protein inhibitor. A sulfhydryl compound such as 2-mercaptoethanol or glutathione was essential for the activation by cyclic GMP, and an extraordinary high concentration of either Mg2+ (100 mM) or Mn2+ (25 mM) was needed for maximal stimulation by cyclic GMP. A polyamine such as spermine, spermidine, or putrescine could substitute partly for the cation. Kinetic analysis indicated that Km for ATP was decreased whereas Ka for cyclic GMP was increased significantly at high concentrations of the cation. The effect of the cation to decrease Km for ATP was not evident in the absence of a sulfhydryl compound. These characteristics of protein kinase G described above were not observed for protein kinase A which was obtained from the same organism.", "contents": "Comparison of mode of activation of guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases from silkworm. Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) partially purified from silkworm pupae was selectively activated by cyclic GMP at lower concentrations. Nevertheless, the enzyme seemed to differ from adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) with respect to the mode of response to cyclic nucleotides. The catalytic activity and cyclic GMP-binding activity were not dissociated by cyclic GMP in a manner similar to that described for protein kinase A. The enzyme was not inhibited by regulatory subunit of protein kinase A nor by protein inhibitor. A sulfhydryl compound such as 2-mercaptoethanol or glutathione was essential for the activation by cyclic GMP, and an extraordinary high concentration of either Mg2+ (100 mM) or Mn2+ (25 mM) was needed for maximal stimulation by cyclic GMP. A polyamine such as spermine, spermidine, or putrescine could substitute partly for the cation. Kinetic analysis indicated that Km for ATP was decreased whereas Ka for cyclic GMP was increased significantly at high concentrations of the cation. The effect of the cation to decrease Km for ATP was not evident in the absence of a sulfhydryl compound. These characteristics of protein kinase G described above were not observed for protein kinase A which was obtained from the same organism."} {"id": "PMID:176154", "title": "Influence of glucagon and cyclic adenosine 3':5'-monophosphate on the phosphorylation of rat liver ribosomal protein S6.", "content": "The administration of glucagon, adenosine 3':5'-monophosphate, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate caused an increase in the phosphorylation of rat liver ribosomes. The increase (approximately 3-fold) was in the protein of the small ribosomal subunit. The proteins were separated by two-dimensional polyacrylamide gel electrophoresis and radioautographs were made of the gels. The effect of the hormone and of the nucleotides was entirely due to an increase in the phosphorylation of the 40 S ribosomal subunit protein S6.", "contents": "Influence of glucagon and cyclic adenosine 3':5'-monophosphate on the phosphorylation of rat liver ribosomal protein S6. The administration of glucagon, adenosine 3':5'-monophosphate, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate caused an increase in the phosphorylation of rat liver ribosomes. The increase (approximately 3-fold) was in the protein of the small ribosomal subunit. The proteins were separated by two-dimensional polyacrylamide gel electrophoresis and radioautographs were made of the gels. The effect of the hormone and of the nucleotides was entirely due to an increase in the phosphorylation of the 40 S ribosomal subunit protein S6."} {"id": "PMID:176155", "title": "Effects of epinephrine and insulin on phosphopeptide metabolism in adipocytes.", "content": "Isolated adipocytes, incubated in the presence of extracellular 32Pi to steady state 32P incorporation into cellular phosphopeptides, were exposed to hormones for 5 min. Epinephrine (10(-6) M) stimulated 32P incorporation into at least 12 major phosphopeptides, distributed in the cytoplasm, endoplasmic reticulum, and plasma membrane. Quantitatively pre-eminent among these were peptides of molecular weight 123,000 and 69,000, each located both in the cytoplasm and endoplasmic reticulum. The effect of epinephrine (10(-7) M) on 32P incorporation into these two peptides was augmented by theophylline (10(-3) M) in a synergistic fashion. Norepinephrine, dibutyryl N6,O2'-dibutyryl adenosine 3':5'-monophosphate, adrenocorticotropic hormone (ACTH) (synthetic 1 to 24 fragment), and glucagon mimicked the effect of epinephrine. Insulin modified adipocyte peptide phosphorylation in two ways. When present as the sole hormone, insulin (100 microunits/ml) consistently and selectively stimulated the 32P incorporation into a peptide of molecular weight 123,000 (endoplasmic reticulum, cytoplasm) without significant alteration in the 32P content of any other major peptide. A second effect of insulin was evident when epinephrine (10(-6) M) was present simultaneously. Insulin significantly inhibited the epinephrine-stimulated phosphorylation of the molecular weight 69,000 (endoplasmic reticulum, cytoplasm) and 26,000 (plasma membrane) peptides. Nevertheless, persistence of insulin-stimulated phosphorylation of the 123,000 peptide in the presence of epinephrine was shown by a 32P content of this peptide that was greater in the presence of both hormones than with either individually. These findings indicate that in intact adipocytes: (a) epinephrine acutely alters the phosphorylation of a large number of adipocyte peptides, partly at least, via activation of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase; (b) insulin opposes several epinephrine-stimulated phosphorylations in a manner consitent with its ability to lower epinephrine-stimulated intracellular cyclic AMP accumulation in adipocytes; and (c) insulin, in addition, exerts a unique stimulatory effect on adipocyte peptide phosphorylation that is independent of its effects on cyclic AMP metabolism and may be medicated by the generation of an as yet undefined intracellular \"messenger\" unique to insulin.", "contents": "Effects of epinephrine and insulin on phosphopeptide metabolism in adipocytes. Isolated adipocytes, incubated in the presence of extracellular 32Pi to steady state 32P incorporation into cellular phosphopeptides, were exposed to hormones for 5 min. Epinephrine (10(-6) M) stimulated 32P incorporation into at least 12 major phosphopeptides, distributed in the cytoplasm, endoplasmic reticulum, and plasma membrane. Quantitatively pre-eminent among these were peptides of molecular weight 123,000 and 69,000, each located both in the cytoplasm and endoplasmic reticulum. The effect of epinephrine (10(-7) M) on 32P incorporation into these two peptides was augmented by theophylline (10(-3) M) in a synergistic fashion. Norepinephrine, dibutyryl N6,O2'-dibutyryl adenosine 3':5'-monophosphate, adrenocorticotropic hormone (ACTH) (synthetic 1 to 24 fragment), and glucagon mimicked the effect of epinephrine. Insulin modified adipocyte peptide phosphorylation in two ways. When present as the sole hormone, insulin (100 microunits/ml) consistently and selectively stimulated the 32P incorporation into a peptide of molecular weight 123,000 (endoplasmic reticulum, cytoplasm) without significant alteration in the 32P content of any other major peptide. A second effect of insulin was evident when epinephrine (10(-6) M) was present simultaneously. Insulin significantly inhibited the epinephrine-stimulated phosphorylation of the molecular weight 69,000 (endoplasmic reticulum, cytoplasm) and 26,000 (plasma membrane) peptides. Nevertheless, persistence of insulin-stimulated phosphorylation of the 123,000 peptide in the presence of epinephrine was shown by a 32P content of this peptide that was greater in the presence of both hormones than with either individually. These findings indicate that in intact adipocytes: (a) epinephrine acutely alters the phosphorylation of a large number of adipocyte peptides, partly at least, via activation of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase; (b) insulin opposes several epinephrine-stimulated phosphorylations in a manner consitent with its ability to lower epinephrine-stimulated intracellular cyclic AMP accumulation in adipocytes; and (c) insulin, in addition, exerts a unique stimulatory effect on adipocyte peptide phosphorylation that is independent of its effects on cyclic AMP metabolism and may be medicated by the generation of an as yet undefined intracellular \"messenger\" unique to insulin."} {"id": "PMID:176156", "title": "Biochemical properties of rat liver mitochondrial aldehyde dehydrogenase with respect to oxidation of formaldehyde.", "content": "The oxidation of formaldehyde by rat liver mitochondria in the presence of 50 mM phosphate was enhanced 2-fold by exogenous NAD+. Absolute requirement of NAD+ for formaldehyde oxidation was demonstrated by depleting the mitochondria of their NAD+ content (4.6 nmol/mg of protein), followed by reincorporation of the NAD+ into the depleted mitochondria. Aldehyde (formaldehyde) dehydrogenase activity was completely abolished in the depleted mitochondria, but the enzyme activity was restored to control levels following reincorporation of the pyridine nucleotide. Phosphate stimulation of formaldehyde oxidation could not be explained fully by the phosphate-induced swelling which enhances membrane permeability to NAD+, since stimulation of the enzyme activity by increased phosphate concentrations was still observed in the absence of exogenous NAD+. The Km for formaldehyde oxidation by the mitochondria was found to be 0.38 nM, a value similar to that obtained with varying concentrations of NAD+; both Vmax values were very similar, giving a value of 70 to 80 nmol/min/mg of protein. The pH optimum for the mitochondrial enzyme was 8.0. Inhibition of the enzyme activity by anaerobiosis was apparently due to the inability of the respiratory chain to oxidize the generated NADH. The inhibition of mitochondrial formaldehyde oxidation by succinate was found to be due to a lowering of the NAD+ level in the mitochondria. Succinate also inhibited acetaldehyde oxidation by the mitochondria. Malonate, a competitive inhibitor of succinic dehydrogenase, blocked the inhibitory effect of succinate. The respiratory chain inhibitors, rotenone, and antimycin A plus succinate, strongly inhibited formaldehyde oxidation by apparently the same mechanism, although the crude enzyme preparation (freed from the membrane) was slightly sensitive to rotenone. The mitochondria were subfractionated, and 85% of the enzyme activity was found in the inner membrane fraction (mitoplast). Furthermore, separation into inner membrane and matrix components indicated a distribution of aldehyde dehydrogenase activity similar to malic dehydrogenase.", "contents": "Biochemical properties of rat liver mitochondrial aldehyde dehydrogenase with respect to oxidation of formaldehyde. The oxidation of formaldehyde by rat liver mitochondria in the presence of 50 mM phosphate was enhanced 2-fold by exogenous NAD+. Absolute requirement of NAD+ for formaldehyde oxidation was demonstrated by depleting the mitochondria of their NAD+ content (4.6 nmol/mg of protein), followed by reincorporation of the NAD+ into the depleted mitochondria. Aldehyde (formaldehyde) dehydrogenase activity was completely abolished in the depleted mitochondria, but the enzyme activity was restored to control levels following reincorporation of the pyridine nucleotide. Phosphate stimulation of formaldehyde oxidation could not be explained fully by the phosphate-induced swelling which enhances membrane permeability to NAD+, since stimulation of the enzyme activity by increased phosphate concentrations was still observed in the absence of exogenous NAD+. The Km for formaldehyde oxidation by the mitochondria was found to be 0.38 nM, a value similar to that obtained with varying concentrations of NAD+; both Vmax values were very similar, giving a value of 70 to 80 nmol/min/mg of protein. The pH optimum for the mitochondrial enzyme was 8.0. Inhibition of the enzyme activity by anaerobiosis was apparently due to the inability of the respiratory chain to oxidize the generated NADH. The inhibition of mitochondrial formaldehyde oxidation by succinate was found to be due to a lowering of the NAD+ level in the mitochondria. Succinate also inhibited acetaldehyde oxidation by the mitochondria. Malonate, a competitive inhibitor of succinic dehydrogenase, blocked the inhibitory effect of succinate. The respiratory chain inhibitors, rotenone, and antimycin A plus succinate, strongly inhibited formaldehyde oxidation by apparently the same mechanism, although the crude enzyme preparation (freed from the membrane) was slightly sensitive to rotenone. The mitochondria were subfractionated, and 85% of the enzyme activity was found in the inner membrane fraction (mitoplast). Furthermore, separation into inner membrane and matrix components indicated a distribution of aldehyde dehydrogenase activity similar to malic dehydrogenase."} {"id": "PMID:176157", "title": "Binding of nitric oxide to reduced L-tryptophan-2,3-dioxygenase as studied by electron paramagnetic resonance.", "content": "Ferrous L-tryptophan-2,3-dioxygenase reacts with nitric oxide both in the presence and in the absence of L-tryptophan. Electron paramagnetic resonance studies suggest that the proximal ligand of the heme is a nitrogen atom, probably from an histidyl residue. The interaction of the protein with substrate changes both the symmetry of the paramagnetic center and the mode of interaction of the iron atom with its two axial ligands, NO and the proximal nitrogen atom. Optical absorption and EPR spectra suggest that the affinity of NO for tryptophan dioxygenase increases in the order: tryptophan dioxygenase, tryptophan dioxygenase + alpha-methyltryptophan, tryptophan diogenase \" 5-hydroxytryptophan, tryptophan dioxygenase + L-tryptophan. A possible correlation between the number of superhyperfine lines in the EPR spectrum and the affinity of the enzyme for NO is discussed.", "contents": "Binding of nitric oxide to reduced L-tryptophan-2,3-dioxygenase as studied by electron paramagnetic resonance. Ferrous L-tryptophan-2,3-dioxygenase reacts with nitric oxide both in the presence and in the absence of L-tryptophan. Electron paramagnetic resonance studies suggest that the proximal ligand of the heme is a nitrogen atom, probably from an histidyl residue. The interaction of the protein with substrate changes both the symmetry of the paramagnetic center and the mode of interaction of the iron atom with its two axial ligands, NO and the proximal nitrogen atom. Optical absorption and EPR spectra suggest that the affinity of NO for tryptophan dioxygenase increases in the order: tryptophan dioxygenase, tryptophan dioxygenase + alpha-methyltryptophan, tryptophan diogenase \" 5-hydroxytryptophan, tryptophan dioxygenase + L-tryptophan. A possible correlation between the number of superhyperfine lines in the EPR spectrum and the affinity of the enzyme for NO is discussed."} {"id": "PMID:176158", "title": "Apparent dispensability of the carbohydrate moiety of human interferon for antiviral activity.", "content": "Human leukocyte and tritium-labeled fibroblast interferons, prepared by induction with Sendai virus and with double-stranded polyinosinic acid.polycytidylic acid respectively, have been studied in relation to the carbohydrate moieties attached to them. These interferons were partially purified by immunoabsorbance and by gel filtration. On treatment with glycosidases, about 80% of the 3H-labeled sugar moieties in this glycoprotein-containing fraction was removed without detectable alteration of the antiviral activity or antibody-binding properties characteristic of interferon. The molecular weight of leukocyte interferon was reduced by about 4000. As others have reported, the heterogeneous character of interferon revealed by isoelectric focusing was greatly reduced by the enzyme treatment.", "contents": "Apparent dispensability of the carbohydrate moiety of human interferon for antiviral activity. Human leukocyte and tritium-labeled fibroblast interferons, prepared by induction with Sendai virus and with double-stranded polyinosinic acid.polycytidylic acid respectively, have been studied in relation to the carbohydrate moieties attached to them. These interferons were partially purified by immunoabsorbance and by gel filtration. On treatment with glycosidases, about 80% of the 3H-labeled sugar moieties in this glycoprotein-containing fraction was removed without detectable alteration of the antiviral activity or antibody-binding properties characteristic of interferon. The molecular weight of leukocyte interferon was reduced by about 4000. As others have reported, the heterogeneous character of interferon revealed by isoelectric focusing was greatly reduced by the enzyme treatment."} {"id": "PMID:176159", "title": "Studies on regulatory factors of ornithine decarboxylase activity during development of mouse mammary epithelium in vitro.", "content": "The activity of ornithine decarboxylase increases markedly in a biphasic manner during the hormone-dependent development of mouse mammary epithelium in vitro. The first peak of activity occurring at 3 to 4 hours of culture was elicited by incubating mammary explants in a culture medium without any added hormones, although addition of insulin or prolactin, or both, caused a greater increase. The emergence of the second peak of activity at about 12 hours depended on the actions of both insulin and prolactin. A second increase in activity could also be effected postmitotically by the delayed addition of prolactin. Studies with actinomycin D and cycloheximide suggest that the first increase in enzyme activity may be effected at a post-transcriptional level, whereas a second increase may be at both transcriptional and translational levels. During the first 3 hours of incubation, there was a rapid, transient increase in cyclic AMP concentration in mammary epithelium. The presence of insulin or prolactin in culture did not affect the change in epithelial cyclic AMP concentration. Addition of several derivatives of cyclic AMP, 0.1 to 0.5 mM, as well as prostaglandin E1, a stimulator of adenylate cyclase, resulted in enhancement of the first increase in enzyme activity. The effect of cyclic nucleotide was additive to that of insulin and prolactin and appears to be mediated at a post-transcriptional level. The stimulatory effect of a lower concentration of both the cyclic nucleotide and prostaglandin E1 was augmented by theophylline, an inhibitor of phosphodiesterase. These results may suggest possible involvement of cyclic AMP in the first increase in enzyme activity that occurs in the absence of any added hormones.", "contents": "Studies on regulatory factors of ornithine decarboxylase activity during development of mouse mammary epithelium in vitro. The activity of ornithine decarboxylase increases markedly in a biphasic manner during the hormone-dependent development of mouse mammary epithelium in vitro. The first peak of activity occurring at 3 to 4 hours of culture was elicited by incubating mammary explants in a culture medium without any added hormones, although addition of insulin or prolactin, or both, caused a greater increase. The emergence of the second peak of activity at about 12 hours depended on the actions of both insulin and prolactin. A second increase in activity could also be effected postmitotically by the delayed addition of prolactin. Studies with actinomycin D and cycloheximide suggest that the first increase in enzyme activity may be effected at a post-transcriptional level, whereas a second increase may be at both transcriptional and translational levels. During the first 3 hours of incubation, there was a rapid, transient increase in cyclic AMP concentration in mammary epithelium. The presence of insulin or prolactin in culture did not affect the change in epithelial cyclic AMP concentration. Addition of several derivatives of cyclic AMP, 0.1 to 0.5 mM, as well as prostaglandin E1, a stimulator of adenylate cyclase, resulted in enhancement of the first increase in enzyme activity. The effect of cyclic nucleotide was additive to that of insulin and prolactin and appears to be mediated at a post-transcriptional level. The stimulatory effect of a lower concentration of both the cyclic nucleotide and prostaglandin E1 was augmented by theophylline, an inhibitor of phosphodiesterase. These results may suggest possible involvement of cyclic AMP in the first increase in enzyme activity that occurs in the absence of any added hormones."} {"id": "PMID:176160", "title": "Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in hepatoma tissue culture cells by pure cholesterol and several cholesterol derivatives. Evidence supporting two distinct mechanisms.20l.", "content": "Pure cholesterol associated in complexes with lipoproteins (whole serum and human low density lipoproteins) or esterified with succinic acid (cholesteryl succinate) and bound to albumin effectively suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells grown in lipoprotein-poor serum medium during short 4-hour) incubation periods. Simultaneous measurments of the kinetics of uptake of radioactive unesterified cholesterol of whole serum and cholesteryl succinate, their conversion to lipid products, and the decay in enzyme activity, suggest that the cholesterol-induced suppression is mediated by the sterol itself rather than by inhibitory lipid products derived from its metabolism. Several cholesterol derivatives such as cholestenone, 7-ketocholesterol, and 7alpha-and 25-hydroxycholesterol also suppress reductase activiy in HTC cells and are significantly more inhibitory than the pure cholesterol preparations. The decrease in enzyme activity produced by cholesterol and its derivatives is concentration-dependent and specific. [1-14C]Oleate incorporation experiments indicate that cholesterol ester formation in HTC cells is not increased at inhibitory concentrations of the steroids. These data suggest that sterol ester formation is not an obligatory process in the feedback control of HMG-CoA reductase activity. The half-life of the reductase (3 to 4 hours) is not significantly changed by cycloheximide, plus or minus whole serum, and cholesteryl succinate. In contrast, the half-life is strongly reduced when HTC cells are incubated with cycloheximide plus maximal concentrations of 25-hydroxycholesterol, 7-ketocholesterol, or cholestenone, resulting in t1/2 values of 24, 36, and 60 min, respectively. Increasing concentrations of whole serum and cholesteryl succinate have no significant effect on the apparent rate constant of inactivation of the enzyme, whereas its apparent rate of synthesis is decreased 3- and 10-fold, respectively. These results are reversed with oxygenated steroid inhibitors. The rate of synthesis of reductase is essentially unchanged as the concentrations of 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone are increased in the culture medium, whereas the apparent rate constant for degradation is increased 9-, 7-, and 3-fold, respectively. HMG-CoA reductase activity in HTC cells thus appears to be modulated by two different mechanisms in which steroid structure is important. Whole serum and cholesteryl succinate specifically decrease the rate of enzyme synthesis, while 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone increase the rate of inactivation of the reductase.", "contents": "Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in hepatoma tissue culture cells by pure cholesterol and several cholesterol derivatives. Evidence supporting two distinct mechanisms.20l. Pure cholesterol associated in complexes with lipoproteins (whole serum and human low density lipoproteins) or esterified with succinic acid (cholesteryl succinate) and bound to albumin effectively suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells grown in lipoprotein-poor serum medium during short 4-hour) incubation periods. Simultaneous measurments of the kinetics of uptake of radioactive unesterified cholesterol of whole serum and cholesteryl succinate, their conversion to lipid products, and the decay in enzyme activity, suggest that the cholesterol-induced suppression is mediated by the sterol itself rather than by inhibitory lipid products derived from its metabolism. Several cholesterol derivatives such as cholestenone, 7-ketocholesterol, and 7alpha-and 25-hydroxycholesterol also suppress reductase activiy in HTC cells and are significantly more inhibitory than the pure cholesterol preparations. The decrease in enzyme activity produced by cholesterol and its derivatives is concentration-dependent and specific. [1-14C]Oleate incorporation experiments indicate that cholesterol ester formation in HTC cells is not increased at inhibitory concentrations of the steroids. These data suggest that sterol ester formation is not an obligatory process in the feedback control of HMG-CoA reductase activity. The half-life of the reductase (3 to 4 hours) is not significantly changed by cycloheximide, plus or minus whole serum, and cholesteryl succinate. In contrast, the half-life is strongly reduced when HTC cells are incubated with cycloheximide plus maximal concentrations of 25-hydroxycholesterol, 7-ketocholesterol, or cholestenone, resulting in t1/2 values of 24, 36, and 60 min, respectively. Increasing concentrations of whole serum and cholesteryl succinate have no significant effect on the apparent rate constant of inactivation of the enzyme, whereas its apparent rate of synthesis is decreased 3- and 10-fold, respectively. These results are reversed with oxygenated steroid inhibitors. The rate of synthesis of reductase is essentially unchanged as the concentrations of 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone are increased in the culture medium, whereas the apparent rate constant for degradation is increased 9-, 7-, and 3-fold, respectively. HMG-CoA reductase activity in HTC cells thus appears to be modulated by two different mechanisms in which steroid structure is important. Whole serum and cholesteryl succinate specifically decrease the rate of enzyme synthesis, while 25-hydroxycholesterol, 7-ketocholesterol, and cholestenone increase the rate of inactivation of the reductase."} {"id": "PMID:176161", "title": "Purification and general properties of guanosine 3':5'-monophosphate-dependent protein kinase from guinea pig fetal lung.", "content": "Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase was purified from the guinea pig fetal lung, a tissue shown to be the richest in this enzyme in all mammalian sources examined, and its general properties studied. The enzyme was purified 150-fold from crude extract by steps of pH 5.4 isoelectric precipitation, Sephadex G-200 filtration, hydroxylapatite treatment and DEAE-cellulose chromatography. The purified enzyme, free from contamination with adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase, had a specific activity at least equivalent to 600-fold purification of the enzyme from the adult lung. The pulmonary enzyme exhibited an absolute requirement of protein kinase modulator (prepared from various mammalian tissues with an exception of skeletal muscle) for its activity. Inhibitor protein of cyclic AMP-dependent protein kinase purified from rabbit skeletal muscle could not stimulate nor inhibit the cyclic GMP target enzyme, indicating the factors from mammalian sources regulating the two classes of protein kinases may not be the same. The enzyme had Ka values of 1.3 times 10(-8) and 3.3 times 10(-8) M for 8-bromo cyclic GMP and cyclic GMP, respectively, compared to 3.0 times 10(-6) M for cyclic AMP. Cyclic GMP lowered the Km of the enzyme for ATP from 6.3 times 10(-5) M in its absence to 2.1 times 10(-5) M in its presence, accompanied by an approximate doubling of the Vmax. The molecular weight of the enzyme (assayed by its catalytic and cyclic GMP-binding abilities) was estimated to be 123,000, corresponding to a sedimendation coefficient of 7.06 S, by means of sucrose density gradient ultracentrifugation. The cyclic GMP-dependent enzyme required Mg2+ and Co2+ for its activity with optimal concentrations of about 30 and 0.7 mM, respectively. The maximal activity seen in the presence of Mg2+, however, was nearly twice as high as that seen in the presence of Co2+. Histones were generally effective substrates for the enzyme, whereas protamine, casein, phosvitin, phosphorylase kinase, and activator protein of phosphodiesterase were not. The cyclic GMP-dependent enzyme exhibited a greater affinity for histones than did the cyclic AMP-dependent enzyme in the presence of Mg2+.", "contents": "Purification and general properties of guanosine 3':5'-monophosphate-dependent protein kinase from guinea pig fetal lung. Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase was purified from the guinea pig fetal lung, a tissue shown to be the richest in this enzyme in all mammalian sources examined, and its general properties studied. The enzyme was purified 150-fold from crude extract by steps of pH 5.4 isoelectric precipitation, Sephadex G-200 filtration, hydroxylapatite treatment and DEAE-cellulose chromatography. The purified enzyme, free from contamination with adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase, had a specific activity at least equivalent to 600-fold purification of the enzyme from the adult lung. The pulmonary enzyme exhibited an absolute requirement of protein kinase modulator (prepared from various mammalian tissues with an exception of skeletal muscle) for its activity. Inhibitor protein of cyclic AMP-dependent protein kinase purified from rabbit skeletal muscle could not stimulate nor inhibit the cyclic GMP target enzyme, indicating the factors from mammalian sources regulating the two classes of protein kinases may not be the same. The enzyme had Ka values of 1.3 times 10(-8) and 3.3 times 10(-8) M for 8-bromo cyclic GMP and cyclic GMP, respectively, compared to 3.0 times 10(-6) M for cyclic AMP. Cyclic GMP lowered the Km of the enzyme for ATP from 6.3 times 10(-5) M in its absence to 2.1 times 10(-5) M in its presence, accompanied by an approximate doubling of the Vmax. The molecular weight of the enzyme (assayed by its catalytic and cyclic GMP-binding abilities) was estimated to be 123,000, corresponding to a sedimendation coefficient of 7.06 S, by means of sucrose density gradient ultracentrifugation. The cyclic GMP-dependent enzyme required Mg2+ and Co2+ for its activity with optimal concentrations of about 30 and 0.7 mM, respectively. The maximal activity seen in the presence of Mg2+, however, was nearly twice as high as that seen in the presence of Co2+. Histones were generally effective substrates for the enzyme, whereas protamine, casein, phosvitin, phosphorylase kinase, and activator protein of phosphodiesterase were not. The cyclic GMP-dependent enzyme exhibited a greater affinity for histones than did the cyclic AMP-dependent enzyme in the presence of Mg2+."} {"id": "PMID:176162", "title": "Essential arginyl residues in mitochondrial adenosine triphosphatase.", "content": "Treatment of either beef heart or rat liver mitochondrial ATPase with the arginine reagent, 2,3-butanedione, resulted in enzyme inactivation. The reaction followed pseudo-first order kinetics until 90 to 95% of the enzyme had been inactivated, and prolonged incubation with butanedione resulted in complete inactivation. When the modification reaction was performed in the presence of ATP, the rate of inactivation was significantly decreased. The kinetics of inactivation indicates that the reaction of 1 molecule of reagent per active site of beef heart mitochondrial ATPase is necessary for inactivation. The loss of ATPase activity was also observed when submitochondrial particles were treated with butanedione. Studies with beef heart mitochondrial ATPase indicated that the inactivation was not due to enzyme dissociation into subunits. Kinetic studies with partially inactivated enzyme demonstrated that the Km values of ITP and of ATP in the presence of HCO3-were similar to the same constants for the control enzyme. When ATP was used as the substrate in the absence of anion activator, the partially inactivated enzyme still exhibited negative cooperativity. Inactivation was also observed when beef heart mitochondrial ATPase was treated with another arginine reagent, phenylglyoxal. The loss of ATPase activity was analyzed in terms of [14C]phenylglyoxal incorporation. From the present studies it is concluded that arginyl residues play an essential role in mitochondrial ATPase, probably at the hydrolytic site.", "contents": "Essential arginyl residues in mitochondrial adenosine triphosphatase. Treatment of either beef heart or rat liver mitochondrial ATPase with the arginine reagent, 2,3-butanedione, resulted in enzyme inactivation. The reaction followed pseudo-first order kinetics until 90 to 95% of the enzyme had been inactivated, and prolonged incubation with butanedione resulted in complete inactivation. When the modification reaction was performed in the presence of ATP, the rate of inactivation was significantly decreased. The kinetics of inactivation indicates that the reaction of 1 molecule of reagent per active site of beef heart mitochondrial ATPase is necessary for inactivation. The loss of ATPase activity was also observed when submitochondrial particles were treated with butanedione. Studies with beef heart mitochondrial ATPase indicated that the inactivation was not due to enzyme dissociation into subunits. Kinetic studies with partially inactivated enzyme demonstrated that the Km values of ITP and of ATP in the presence of HCO3-were similar to the same constants for the control enzyme. When ATP was used as the substrate in the absence of anion activator, the partially inactivated enzyme still exhibited negative cooperativity. Inactivation was also observed when beef heart mitochondrial ATPase was treated with another arginine reagent, phenylglyoxal. The loss of ATPase activity was analyzed in terms of [14C]phenylglyoxal incorporation. From the present studies it is concluded that arginyl residues play an essential role in mitochondrial ATPase, probably at the hydrolytic site."} {"id": "PMID:176163", "title": "Basement membrane procollagen is not converted to collagen in organ cultures of parietal yolk sac endoderm.", "content": "Basement membrane procollagen biosynthesis was studied in organ cultures of embryonic rat parietal yolk sac endoderm by following [14C]proline incorporation into nondialyzable proteins. After reduction with 2-mercaptoethanol the 14C-proteins synthesized were characterized by agarose gel filtration and disc electrophoresis in the presence of sodium dodecyl sulfate. The labeled procollagen was identified by its content of hydroxy[14C]proline, its sensitivity to digestion with bacterial collagenase, and its resistance to digestion with pepsin. In cultures which were continuously labeled for periods from 6 hours to 4 days, the pro-alpha chains consistently eluted as a single peak with an apparent molecular weight of 160,000. After pepsin digestion the resultant alpha chains had an apparent molecular weight between 125,000 and 140,000. This suggests that basement membrane procollagen either contains non-triple helical pepsin-resistant regions or a triple helical region which is larger than the corresponding region of interstitial procollagen. Two experiments were performed to determine whether the chains of newly synthesized basement membrane procollagen were cleaved to a smaller molecular species. In the first, the hydroxylation and secretion of procollagen were blocked with alpha, alpha'-dipyridyl, and the resulting intracellular chains of basement membrane protocollagen were found to co-elute with fully hydroxylated and secreted pro-alpha chains. In the second, cultures were labeled for 1 day and chased for 3 days with unlabeled medium. Autoradiography had shown that most of the label was chased into new basement membrane. Agarose chromotography showed that after 3-day chase the pro-alpha chains still eluted with an apparent molecular weight of 160,000. Thus, the data indicated that basement membrane procollagen was deposited in new basement membrane without undergoing a time-dependent extracellular conversion.", "contents": "Basement membrane procollagen is not converted to collagen in organ cultures of parietal yolk sac endoderm. Basement membrane procollagen biosynthesis was studied in organ cultures of embryonic rat parietal yolk sac endoderm by following [14C]proline incorporation into nondialyzable proteins. After reduction with 2-mercaptoethanol the 14C-proteins synthesized were characterized by agarose gel filtration and disc electrophoresis in the presence of sodium dodecyl sulfate. The labeled procollagen was identified by its content of hydroxy[14C]proline, its sensitivity to digestion with bacterial collagenase, and its resistance to digestion with pepsin. In cultures which were continuously labeled for periods from 6 hours to 4 days, the pro-alpha chains consistently eluted as a single peak with an apparent molecular weight of 160,000. After pepsin digestion the resultant alpha chains had an apparent molecular weight between 125,000 and 140,000. This suggests that basement membrane procollagen either contains non-triple helical pepsin-resistant regions or a triple helical region which is larger than the corresponding region of interstitial procollagen. Two experiments were performed to determine whether the chains of newly synthesized basement membrane procollagen were cleaved to a smaller molecular species. In the first, the hydroxylation and secretion of procollagen were blocked with alpha, alpha'-dipyridyl, and the resulting intracellular chains of basement membrane protocollagen were found to co-elute with fully hydroxylated and secreted pro-alpha chains. In the second, cultures were labeled for 1 day and chased for 3 days with unlabeled medium. Autoradiography had shown that most of the label was chased into new basement membrane. Agarose chromotography showed that after 3-day chase the pro-alpha chains still eluted with an apparent molecular weight of 160,000. Thus, the data indicated that basement membrane procollagen was deposited in new basement membrane without undergoing a time-dependent extracellular conversion."} {"id": "PMID:176165", "title": "Complications of arterial puncture in anticoagulated patients.", "content": "Thirteen patients who were receiving heparin in therapeutic doses had complications after femoral or brachial arterial puncture as follows: hematomas resulting in skin slough or infection in two, neuropathies of the median nerve in two and of the femoral nerve in two, and ischemia of the forearm muscles in seven. Since arterial puncture to determine blood gases in patients anticoagulated for pulmonary emboli can be dangerous, alternate means to establish the diagnosis are recommended. Early recognition and treatment of complications are essential.", "contents": "Complications of arterial puncture in anticoagulated patients. Thirteen patients who were receiving heparin in therapeutic doses had complications after femoral or brachial arterial puncture as follows: hematomas resulting in skin slough or infection in two, neuropathies of the median nerve in two and of the femoral nerve in two, and ischemia of the forearm muscles in seven. Since arterial puncture to determine blood gases in patients anticoagulated for pulmonary emboli can be dangerous, alternate means to establish the diagnosis are recommended. Early recognition and treatment of complications are essential."} {"id": "PMID:176166", "title": "[Success or failure factors in the treatment of insulin-secreting nesidioblastomas].", "content": "The authors report 5 cases of insulin- secreting nesidioblastoma which is not an exceptional tumour but may be suspected clinically before being confirmed in the laboratory. Fasting hypoglycemia or hyper-insulinism may be present, leading to arteriography and surgical exploration. The only valid forms of treatment are enucleation of the tumour or pancreatectomy, depending on whether it is situated on the right or on the left. The authors consider removal must be complete, if not, medical treatment should be preferred.", "contents": "[Success or failure factors in the treatment of insulin-secreting nesidioblastomas]. The authors report 5 cases of insulin- secreting nesidioblastoma which is not an exceptional tumour but may be suspected clinically before being confirmed in the laboratory. Fasting hypoglycemia or hyper-insulinism may be present, leading to arteriography and surgical exploration. The only valid forms of treatment are enucleation of the tumour or pancreatectomy, depending on whether it is situated on the right or on the left. The authors consider removal must be complete, if not, medical treatment should be preferred."} {"id": "PMID:176167", "title": "[Tumors of the carotid body. Diagnostic and therapeutic considerations. Apropos of a case].", "content": "The authors report a new case of carotid body tumour operated on, in a 26 year old woman. Recalling the main clinical and histological characteristics of these tumours, they emphasize the importance of pre-operative assessment and the decisive value of arteriography. Modern techniques of surgery of the carotid bodies permit one to face the risk of damage during removal. They re-emphasize the necessity of surgical treatment able to ensure a cure. Finally, emphasizeing the special gravity of advanced tumours (group III), they condemn a conservative attitude and recommended operation as early as possible.", "contents": "[Tumors of the carotid body. Diagnostic and therapeutic considerations. Apropos of a case]. The authors report a new case of carotid body tumour operated on, in a 26 year old woman. Recalling the main clinical and histological characteristics of these tumours, they emphasize the importance of pre-operative assessment and the decisive value of arteriography. Modern techniques of surgery of the carotid bodies permit one to face the risk of damage during removal. They re-emphasize the necessity of surgical treatment able to ensure a cure. Finally, emphasizeing the special gravity of advanced tumours (group III), they condemn a conservative attitude and recommended operation as early as possible."} {"id": "PMID:176168", "title": "Rapid and sensitive liquid chromatographic determination of carbamazepine suitable for use in monitoring multiple-drug anticonvulsant therapy.", "content": "A rapid, sensitive and selective method for the determination of carbamazepine and its major metabolite in plasma has been developed. Other commonly used anticonvulsants can be determined in the same procedure without interference. After extraction with dichloromethane, the components are separated by high-pressure liquid chromatography without further clean-up or concentration on a column packed with small-particle silica gel. The mean recovery from plasma is 98.6% with a relative standard deviation of 1.6%. The detection limit for carbamazepine is approximately 2 ng/ml, requiring 1 ml of plasma.", "contents": "Rapid and sensitive liquid chromatographic determination of carbamazepine suitable for use in monitoring multiple-drug anticonvulsant therapy. A rapid, sensitive and selective method for the determination of carbamazepine and its major metabolite in plasma has been developed. Other commonly used anticonvulsants can be determined in the same procedure without interference. After extraction with dichloromethane, the components are separated by high-pressure liquid chromatography without further clean-up or concentration on a column packed with small-particle silica gel. The mean recovery from plasma is 98.6% with a relative standard deviation of 1.6%. The detection limit for carbamazepine is approximately 2 ng/ml, requiring 1 ml of plasma."} {"id": "PMID:176169", "title": "Metabolic effects of parathyroidectomy in asymptomatic primary hyperparathyroidism.", "content": "Effects of parathyroidectomy on parathyroid function and calcium (Ca) metabolism were carefully evaluated in 6 patients with primary hyperparathyroidism without symptoms normally attributed to the disease and in 7 with bone disease or nephrolithiasis. Before parathyroidectomy, both groups of patients demonstrated evidence of the sequelae of parathyroid hormone (PTH) excess, since they presented one or more of the following features: low bone density by 125I-photon absorption, hypercalciuria (urinary Ca greater than 200 mg/day on an intake of 400 mg/day), negative Ca balance (absorbed Ca less than urinary Ca), elevated fasting urinary Ca greater than 0.2 mg/mg creatinine for a night-time sample after a 6-hour fast), and decreased renal function (creatinine clearance of less than 65 ml/min). Following parathyroidectomy, most of these deleterious effects were reversed commensurate with the return of immunoreactive serum PTH, serum Ca, and urinary cyclic AMP toward normal. These quantitative non-invasive techniques may be useful for the initial evaluation and follow-up of patients with asymptomatic primary hyperparathyroidism.", "contents": "Metabolic effects of parathyroidectomy in asymptomatic primary hyperparathyroidism. Effects of parathyroidectomy on parathyroid function and calcium (Ca) metabolism were carefully evaluated in 6 patients with primary hyperparathyroidism without symptoms normally attributed to the disease and in 7 with bone disease or nephrolithiasis. Before parathyroidectomy, both groups of patients demonstrated evidence of the sequelae of parathyroid hormone (PTH) excess, since they presented one or more of the following features: low bone density by 125I-photon absorption, hypercalciuria (urinary Ca greater than 200 mg/day on an intake of 400 mg/day), negative Ca balance (absorbed Ca less than urinary Ca), elevated fasting urinary Ca greater than 0.2 mg/mg creatinine for a night-time sample after a 6-hour fast), and decreased renal function (creatinine clearance of less than 65 ml/min). Following parathyroidectomy, most of these deleterious effects were reversed commensurate with the return of immunoreactive serum PTH, serum Ca, and urinary cyclic AMP toward normal. These quantitative non-invasive techniques may be useful for the initial evaluation and follow-up of patients with asymptomatic primary hyperparathyroidism."} {"id": "PMID:176170", "title": "Effect of angiotensin II on cyclic guanosine monophosphate and cyclic adenosine monophosphate in human plasma.", "content": "Infusion of alpha-adrenergic catecholamines increases plasma cyclic guanosine monophosphate (pcGMP), raising the possibility that the pressor effect of these agents may be mediated by cyclic GMP. We infused pressor doses of angiotensin II in 10 studies in 8 normal subject and measured pcGMP and plasma cyclic adenosine monophosphate (pcAMP) by radioimmunoassay. After 120 minutes of infusion, mean pcGMP was 128 +/- 31% (SE) higher than baseline values (P less than 0.01) while pcAMP was increased 30 +/- 10% (P less than 0.05).", "contents": "Effect of angiotensin II on cyclic guanosine monophosphate and cyclic adenosine monophosphate in human plasma. Infusion of alpha-adrenergic catecholamines increases plasma cyclic guanosine monophosphate (pcGMP), raising the possibility that the pressor effect of these agents may be mediated by cyclic GMP. We infused pressor doses of angiotensin II in 10 studies in 8 normal subject and measured pcGMP and plasma cyclic adenosine monophosphate (pcAMP) by radioimmunoassay. After 120 minutes of infusion, mean pcGMP was 128 +/- 31% (SE) higher than baseline values (P less than 0.01) while pcAMP was increased 30 +/- 10% (P less than 0.05)."} {"id": "PMID:176171", "title": "The urinary excretion of glucosiduronates of cortisol and cortisone.", "content": "Cortisol and cortisone glucosiduronic acids were synthesised in a 14C-labelled from and utilised in a double-isotope derivative procedure for the analysis of cortisol glucosiduronate (FG) and cortisone glucosiduronate (EG) in human urine. Normal adults were found to excrete between 16 and 100 mug/24 h of FG (n = 14) and between 55 and 120 mug/24 h of EG (n = 15). Elevated values were observed in subjects with Cushing's syndrome and following ACTH stimulation. Abnormal excretion was noted in one patient with hepatic cirrhosis and in one case of cholestatic jaundice. The ratio FG/EG was markedly increased after ACTH stimulation and, in the normal group, was positively correlated to a highly significant degree (P less than 0.001) with FG excretion. These two observations suggest that EG excretion is less sensitive than FG excretion to variations in cortisol production.", "contents": "The urinary excretion of glucosiduronates of cortisol and cortisone. Cortisol and cortisone glucosiduronic acids were synthesised in a 14C-labelled from and utilised in a double-isotope derivative procedure for the analysis of cortisol glucosiduronate (FG) and cortisone glucosiduronate (EG) in human urine. Normal adults were found to excrete between 16 and 100 mug/24 h of FG (n = 14) and between 55 and 120 mug/24 h of EG (n = 15). Elevated values were observed in subjects with Cushing's syndrome and following ACTH stimulation. Abnormal excretion was noted in one patient with hepatic cirrhosis and in one case of cholestatic jaundice. The ratio FG/EG was markedly increased after ACTH stimulation and, in the normal group, was positively correlated to a highly significant degree (P less than 0.001) with FG excretion. These two observations suggest that EG excretion is less sensitive than FG excretion to variations in cortisol production."} {"id": "PMID:176172", "title": "Normal gestation and diminished androgen responsiveness in an untreated patient with 21-hydroxylase deficiency.", "content": "A 22-year-old woman with 21-hydroxylase deficiency but minimal clinical evidence of androgenization was studied. She had conceived twice and had borne a normal male infant without therapy of any kind. The diagnosis of 21-hydroxylase deficiency was substantiated by the findings of 17-ketosteroid and pregnanetriol excretions of 18.1 and 8.1 mg/24 hours, respectively. Adequate basal compensation was indicated by a fasting plasma cortisol of 17.5 mug/dl. Plasma ACTH (207 pg/ml), testosterone (216 ng/dl) delta4-androstenedione (649 mg/dl), progesterone (249 ng/dl) and 17alpha-hydroxyprogesterone (4820 ng/dl) were all significantly elevated.", "contents": "Normal gestation and diminished androgen responsiveness in an untreated patient with 21-hydroxylase deficiency. A 22-year-old woman with 21-hydroxylase deficiency but minimal clinical evidence of androgenization was studied. She had conceived twice and had borne a normal male infant without therapy of any kind. The diagnosis of 21-hydroxylase deficiency was substantiated by the findings of 17-ketosteroid and pregnanetriol excretions of 18.1 and 8.1 mg/24 hours, respectively. Adequate basal compensation was indicated by a fasting plasma cortisol of 17.5 mug/dl. Plasma ACTH (207 pg/ml), testosterone (216 ng/dl) delta4-androstenedione (649 mg/dl), progesterone (249 ng/dl) and 17alpha-hydroxyprogesterone (4820 ng/dl) were all significantly elevated."} {"id": "PMID:176173", "title": "Angiotensin I-converting enzyme and angiotensin II levels in women receiving an oral contraceptive.", "content": "In 11 healthy, normotensive young women taking contraceptive medication (Enovid) for at least one year, plasma levels of angiotensin II were significantly higher than in healthy male and female controls. No significant difference was seen in the serum activity of angiotensin I-converting enzyme measured in vitro. Although serum angiotensin I converting enzyme activity is stimulated in several conditions in which other components of renin-angiotensin-aldosterone system are increased, this is not the case during administration of estrogens.", "contents": "Angiotensin I-converting enzyme and angiotensin II levels in women receiving an oral contraceptive. In 11 healthy, normotensive young women taking contraceptive medication (Enovid) for at least one year, plasma levels of angiotensin II were significantly higher than in healthy male and female controls. No significant difference was seen in the serum activity of angiotensin I-converting enzyme measured in vitro. Although serum angiotensin I converting enzyme activity is stimulated in several conditions in which other components of renin-angiotensin-aldosterone system are increased, this is not the case during administration of estrogens."} {"id": "PMID:176174", "title": "Comparison of a microneutralization test in cell culture and virus neutralization test in embryonated eggs for determining infectious bronchitis virus antibodies.", "content": "A microneutralization test (MNT) system utilizing cytopathic effect end points was effective in determing neutralization indexes for infectious bronchitis virus antibodies. The system is reproducible within 1 index unit at the 95% level of probability. Comparison of the MNT to tests in eggs resulted in a positive correlation (B =0.81), which was significant (P greater than 0.01). The quantitative dose-response relationship of the MNT is linear (P greater than 0.005), with the 95% prediction limits fitting between one 10-fold dilution.", "contents": "Comparison of a microneutralization test in cell culture and virus neutralization test in embryonated eggs for determining infectious bronchitis virus antibodies. A microneutralization test (MNT) system utilizing cytopathic effect end points was effective in determing neutralization indexes for infectious bronchitis virus antibodies. The system is reproducible within 1 index unit at the 95% level of probability. Comparison of the MNT to tests in eggs resulted in a positive correlation (B =0.81), which was significant (P greater than 0.01). The quantitative dose-response relationship of the MNT is linear (P greater than 0.005), with the 95% prediction limits fitting between one 10-fold dilution."} {"id": "PMID:176175", "title": "Plaque assay of Sendai virus in monolayers of a clonal line of porcine kidney cells.", "content": "The MN strain of Sendai virus formed distinct plaques in monolayers of PS-Y15 cells, an established porcine kidney cell line. The plaque-forming ability was neutralized by specific antibody to the virus. A linear relationship was found between the concentration of virus and the number of plaques. The sensitivity of this assay was about equal to that of the in ovo titration. When applied to the serum neutralization test, the end points obtained were comparable to those of the hemagglutination-inhibition and complement-fixation tests.", "contents": "Plaque assay of Sendai virus in monolayers of a clonal line of porcine kidney cells. The MN strain of Sendai virus formed distinct plaques in monolayers of PS-Y15 cells, an established porcine kidney cell line. The plaque-forming ability was neutralized by specific antibody to the virus. A linear relationship was found between the concentration of virus and the number of plaques. The sensitivity of this assay was about equal to that of the in ovo titration. When applied to the serum neutralization test, the end points obtained were comparable to those of the hemagglutination-inhibition and complement-fixation tests."} {"id": "PMID:176176", "title": "Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.", "content": "To disclose a parathyroid-independent calcium modulation of phosphate transport along the nephron, the effect of increasing plasma calcium concentration to subnormal levels in rats 6 days after parathyroidectomy (chronic PTX) was studied. Fractional phosphate reabsorption was significantly increased. The whole kidney response to calcium infusion was similar whether or not the thyroid gland was removed, which suggests that calcitonin is not involved. The micropuncture study indicated an increase in the reabsorptive capacity for phosphate (absolute reabsorption/absolute delivered phosphate per nephron segment) in the proximal tubule, the loop, and the terminal nephron when calcium was infused. Thus, the level of plasma calcium or some related factor affects the phosphate transport by the tubule independently of parathyroid hormone. With calcium infusion, the profile of phosphate reabsorption along the nephron became close to that of acutely parathyroidectomized rats, but with persisting differences. The level of plasma calcium concentration may partly account for the differences between the acute and the chronic steps of parathyroidectomy. The role of possible interferences between alterations of extracellular calcium concentration or some related factor and the adenylate cyclase-cyclic AMP system in such an action of calcium was evaluated. Cyclic AMP was infused so as to achieve a 10(-6) M plasma concentration. Combined infusions of calcium and cyclic AMP were also performed. The results are compatible with calcium inhibition of adenylate cyclase, although they do not rule out a direct action of calcium.", "contents": "Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron. To disclose a parathyroid-independent calcium modulation of phosphate transport along the nephron, the effect of increasing plasma calcium concentration to subnormal levels in rats 6 days after parathyroidectomy (chronic PTX) was studied. Fractional phosphate reabsorption was significantly increased. The whole kidney response to calcium infusion was similar whether or not the thyroid gland was removed, which suggests that calcitonin is not involved. The micropuncture study indicated an increase in the reabsorptive capacity for phosphate (absolute reabsorption/absolute delivered phosphate per nephron segment) in the proximal tubule, the loop, and the terminal nephron when calcium was infused. Thus, the level of plasma calcium or some related factor affects the phosphate transport by the tubule independently of parathyroid hormone. With calcium infusion, the profile of phosphate reabsorption along the nephron became close to that of acutely parathyroidectomized rats, but with persisting differences. The level of plasma calcium concentration may partly account for the differences between the acute and the chronic steps of parathyroidectomy. The role of possible interferences between alterations of extracellular calcium concentration or some related factor and the adenylate cyclase-cyclic AMP system in such an action of calcium was evaluated. Cyclic AMP was infused so as to achieve a 10(-6) M plasma concentration. Combined infusions of calcium and cyclic AMP were also performed. The results are compatible with calcium inhibition of adenylate cyclase, although they do not rule out a direct action of calcium."} {"id": "PMID:176177", "title": "Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis.", "content": "The biochemical mechanisms by which a genetically determined deficiency of adenosine deaminase leads to immunodeficiency are still poorly understood and prompted this study. We have examined the effects of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) upon the response of human peripheral blood mononuclear cells to the mitogen concanavalin A (Con A). Cells isolated from normal volunteers were incubated in microtiter plates in the presence of various inhibitors, and the incorporation of tritrated thymidine or leucine into macromolecular material was measured after 64 h. EHNA at a concentration of 0.3 muM, which inhibited 90% of the adenosine deaminase (ADA) activity in a mononuclear preparation, impaired the incorporation of tritrated leucine into protein; 100 muM EHNA was the minimal concentration that inhibited thymidine uptake. The addition of 15 muM adenosine or 10 muM cyclic AMP to Con A-stimulated lymphocytes inhibited leucine uptake, while millimolar concentrations were required to inhibit thymidine uptake. Lower doses of adenosine and cyclic AMP stimulated thymidine incorporation. The inhibition of thymidine uptake observed with millimolar concentrations of adenosine was independent of the type of mitogen (pokeweed or Con A), the concentration of mitogen, or the medium used, but could be increased if the cells were cultured in a serum with reduced levels of adenosine deaminase. Washout experiments failed to demonstrate a critical period early in immune induction during which adenosine exerted its inhibitory effects. Noninhibitory doses of EHNA potentiated the effects of adenosine and cyclic AMP on leucine and thymidine uptake. EHNA at a concentration of 50 muM also potentiated the inhibitory effects on thymidine uptake of dibutyryl cyclic AMP, butyric acid, norepinephrine, and isoproterenol, but not theophylline. When mitogenesis was assayed by leucine incorporations, no synergy between EHNA and these compounds was apparent. Uridine relieved to some extent the inhibition of blastogenesis produced by adenosine and cyclic AMP, but not by dibutyryl cyclic AMP, norepinephreine, isoproterenol, or theophylline. Neither uridine alone nor uridine plus adenosine protected lymphocytes from the inhibitory effects of EHNA.", "contents": "Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis. The biochemical mechanisms by which a genetically determined deficiency of adenosine deaminase leads to immunodeficiency are still poorly understood and prompted this study. We have examined the effects of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) upon the response of human peripheral blood mononuclear cells to the mitogen concanavalin A (Con A). Cells isolated from normal volunteers were incubated in microtiter plates in the presence of various inhibitors, and the incorporation of tritrated thymidine or leucine into macromolecular material was measured after 64 h. EHNA at a concentration of 0.3 muM, which inhibited 90% of the adenosine deaminase (ADA) activity in a mononuclear preparation, impaired the incorporation of tritrated leucine into protein; 100 muM EHNA was the minimal concentration that inhibited thymidine uptake. The addition of 15 muM adenosine or 10 muM cyclic AMP to Con A-stimulated lymphocytes inhibited leucine uptake, while millimolar concentrations were required to inhibit thymidine uptake. Lower doses of adenosine and cyclic AMP stimulated thymidine incorporation. The inhibition of thymidine uptake observed with millimolar concentrations of adenosine was independent of the type of mitogen (pokeweed or Con A), the concentration of mitogen, or the medium used, but could be increased if the cells were cultured in a serum with reduced levels of adenosine deaminase. Washout experiments failed to demonstrate a critical period early in immune induction during which adenosine exerted its inhibitory effects. Noninhibitory doses of EHNA potentiated the effects of adenosine and cyclic AMP on leucine and thymidine uptake. EHNA at a concentration of 50 muM also potentiated the inhibitory effects on thymidine uptake of dibutyryl cyclic AMP, butyric acid, norepinephrine, and isoproterenol, but not theophylline. When mitogenesis was assayed by leucine incorporations, no synergy between EHNA and these compounds was apparent. Uridine relieved to some extent the inhibition of blastogenesis produced by adenosine and cyclic AMP, but not by dibutyryl cyclic AMP, norepinephreine, isoproterenol, or theophylline. Neither uridine alone nor uridine plus adenosine protected lymphocytes from the inhibitory effects of EHNA."} {"id": "PMID:176178", "title": "Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction.", "content": "In the majority of patients with gout and excessive uric acid production, underlying enzyme abnormalities have not been identified. In the present study, measurement of both the rate of generation and concentration of phosphoribosylpyrophosphate (PP-ribose-P) and the concentration of ribose-5-phosphate in cultured cells were undertaken to establish a classification of purine overproducers to direct study of additional enzyme defects. Fibroblasts were cultured from 24 individuals assigned to 4 groups: group 1, 5 normal controls; group 2, 5 patients with gout and normal dialy urinary uric acid excretion (gouty controls); group 3, 7 patients with well-defined enzyme abnormalities and excessive urinary acid excretion (4 with hypoxanthine-guanine phosphoribosyltransferase deficiency and 3 with excessive PP-ribose-P synthetase activity); and group 4, 7 patients with gout and excessive uric acid excretion but without grossly abnormal activities of the above enzymes in erythrocyte lysates. In all 14 fibroblast strains from patients showing excessive production of uric acid (groups 3 and 4), rates of purine synthesis de novo and PP-ribose-P concentrations exceeded values for cells from control groups. Cells from group 3 patients with hypoxanthine-guanine phosphoribosyltransferase deficiency showed normal PP-ribose-P generation, while those with excessive PP-ribose-P synthetase activity demonstrated increased generation of this regulatory substrate. All strains from group 3 patients had normal ribose-5-phosphate concentrations. Five cell strains from group 4 patients showed one of the two patterns of abnormalities in these measurements seen in strains from group 3 patients: two resembled hypoxanthine-guanine phosphoribosyltransferase-deficient cells, and three resembled cells with excessive PP-ribose-P synthetase activity. Analyses of erythrocyte enzyme preparations from two of these patients in group 4 have led to identification of a kinetic variant of each enzyme as predicted from the foregoing patterns. Two additional group 4 cell lines that showed increased ribose-5-phosphate concentrations in addition to increased PP-ribose-P concentrations and generation were classified in a separate subgroup, since in the individuals excessive purine synthesis appeared to result from increases ribose-5-phosphate concentration, leading to increased availability of PP-ribose-P. No abnormality in either hypoxanthine-guanine phosphoribosyltransferase or PP-ribose-P synthetase has been found in erythrocyte preparations from one patient so classified.", "contents": "Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction. In the majority of patients with gout and excessive uric acid production, underlying enzyme abnormalities have not been identified. In the present study, measurement of both the rate of generation and concentration of phosphoribosylpyrophosphate (PP-ribose-P) and the concentration of ribose-5-phosphate in cultured cells were undertaken to establish a classification of purine overproducers to direct study of additional enzyme defects. Fibroblasts were cultured from 24 individuals assigned to 4 groups: group 1, 5 normal controls; group 2, 5 patients with gout and normal dialy urinary uric acid excretion (gouty controls); group 3, 7 patients with well-defined enzyme abnormalities and excessive urinary acid excretion (4 with hypoxanthine-guanine phosphoribosyltransferase deficiency and 3 with excessive PP-ribose-P synthetase activity); and group 4, 7 patients with gout and excessive uric acid excretion but without grossly abnormal activities of the above enzymes in erythrocyte lysates. In all 14 fibroblast strains from patients showing excessive production of uric acid (groups 3 and 4), rates of purine synthesis de novo and PP-ribose-P concentrations exceeded values for cells from control groups. Cells from group 3 patients with hypoxanthine-guanine phosphoribosyltransferase deficiency showed normal PP-ribose-P generation, while those with excessive PP-ribose-P synthetase activity demonstrated increased generation of this regulatory substrate. All strains from group 3 patients had normal ribose-5-phosphate concentrations. Five cell strains from group 4 patients showed one of the two patterns of abnormalities in these measurements seen in strains from group 3 patients: two resembled hypoxanthine-guanine phosphoribosyltransferase-deficient cells, and three resembled cells with excessive PP-ribose-P synthetase activity. Analyses of erythrocyte enzyme preparations from two of these patients in group 4 have led to identification of a kinetic variant of each enzyme as predicted from the foregoing patterns. Two additional group 4 cell lines that showed increased ribose-5-phosphate concentrations in addition to increased PP-ribose-P concentrations and generation were classified in a separate subgroup, since in the individuals excessive purine synthesis appeared to result from increases ribose-5-phosphate concentration, leading to increased availability of PP-ribose-P. No abnormality in either hypoxanthine-guanine phosphoribosyltransferase or PP-ribose-P synthetase has been found in erythrocyte preparations from one patient so classified."} {"id": "PMID:176179", "title": "Effects of a 3-day fast and of ethanol on splanchnic metabolism of FFA, amino acids, and carbohydrates in healthy young men.", "content": "Splanchnic metabolism was studied to quantify changes underlying the fatty liver, hyperlipemia, and hypoglycemia produced by ethanol. Four subjects fasted for 15 h were compared with five subjects fasted for 69 h under basal conditions and during continuous intravenous infusion of sufficient ethanol to give a concentration of 3-5 mM in arterial blood plasma. Splanchnic storage of fatty acids was estimated from the difference between uptake of FFA and secretion of derived products. Basal values for splanchnic uptake of FFA were twofold higher after the 69-h fast while splanchnic storage of fatty acids and production of ketone bodies increased threefold. Values for basal secreation into the blood of triglycerides derived from FFA were similar in the two groups. In both nutritional states, the fraction of FFA taken up in the splanchnic region oxidized to ketone bodies and to CO2 fell when ethanol was given because of preferential oxidation of ethanol to acetate, and the fraction esterified rose. However, systemic transport and splanchnic uptake of FFA fell with ethanol in subjects fasted 15 h, so that neither storage of triglycerides in splanchnic tissues nor secretion into the blood increased. In subjects fasted 69 h, ethanol increased transport of FFA and splanchnic storage of fat. In all but one subject it also increased secretion of triglycerides into the blood. The concentration of glucose in blood fell during ethanol infusion in all five subjects undergoing the 69-h fast. Mean splanchnic glucose production was maintained at about one-half of the pre-ethanol value, despite virtual cessation of splanchnic uptake of lactate and of those amino acids that are metabolized via malate. Quantitative estimates of extrasplanchnic metabolism suggest that enhanced formation of alpha-glycerophosphate from glucose, in addition to impaired hepatic gluconeogenesis, may contribute to ethanol-induced hypoglycemia in man.", "contents": "Effects of a 3-day fast and of ethanol on splanchnic metabolism of FFA, amino acids, and carbohydrates in healthy young men. Splanchnic metabolism was studied to quantify changes underlying the fatty liver, hyperlipemia, and hypoglycemia produced by ethanol. Four subjects fasted for 15 h were compared with five subjects fasted for 69 h under basal conditions and during continuous intravenous infusion of sufficient ethanol to give a concentration of 3-5 mM in arterial blood plasma. Splanchnic storage of fatty acids was estimated from the difference between uptake of FFA and secretion of derived products. Basal values for splanchnic uptake of FFA were twofold higher after the 69-h fast while splanchnic storage of fatty acids and production of ketone bodies increased threefold. Values for basal secreation into the blood of triglycerides derived from FFA were similar in the two groups. In both nutritional states, the fraction of FFA taken up in the splanchnic region oxidized to ketone bodies and to CO2 fell when ethanol was given because of preferential oxidation of ethanol to acetate, and the fraction esterified rose. However, systemic transport and splanchnic uptake of FFA fell with ethanol in subjects fasted 15 h, so that neither storage of triglycerides in splanchnic tissues nor secretion into the blood increased. In subjects fasted 69 h, ethanol increased transport of FFA and splanchnic storage of fat. In all but one subject it also increased secretion of triglycerides into the blood. The concentration of glucose in blood fell during ethanol infusion in all five subjects undergoing the 69-h fast. Mean splanchnic glucose production was maintained at about one-half of the pre-ethanol value, despite virtual cessation of splanchnic uptake of lactate and of those amino acids that are metabolized via malate. Quantitative estimates of extrasplanchnic metabolism suggest that enhanced formation of alpha-glycerophosphate from glucose, in addition to impaired hepatic gluconeogenesis, may contribute to ethanol-induced hypoglycemia in man."} {"id": "PMID:176180", "title": "Reduced sensitivity of the hepatic adenylate cyclase-cyclic AMP system to glucagon during sustained hormonal stimulation.", "content": "Hormone-induced desensitization of hormonal regulation of cyclic AMP (cAMP) content has been described in a number of tissues. In the present study, we examined responses of rat liver to glucagon after periods of sustained exposure to the hormone in vivo and in vitro. In intact anesthetized rats infused with glucagon (50 ng/min) for 1 h or more and in liver slices incubated with the hormone (10 muM) for this period, hepatic cAMP responsiveness to glucagon was significantly blunted compared with that of tissue exposed to the hormone for shorter periods. The reduction in hepatic cAMP responsiveness to glucagon appeared to be fully expressed by 2 h. With the doses of hormone employed, the sequential alterations in hepatic responsiveness seemed to be limited to the cAMP system, since other parameters of glucagon action did not wane with time. Diminished hepatic cAMP responsiveness during sustained hormonal exposure could not be attributed to decreased glucagon availability, accelerated extracellular release of cAMP, hepatic ATP depletion, or enhanced phosphodiesterase activity. Studies in vitro suggested that modulation of the cAMP response occurred at the level of adenylate cyclase (AC). During sustained exposure of hepatic slices to glucagon, reductions in glucagon-responsive AC correlated temporally with those in cAMP and both changes were reversible. Alterations in glucagon-responsive AC were demonstrated over a wide range of ATP (10 muM-0.1 mM) and glucagon (10 nM-5 MM) concentrations in the cyclase reaction mixture, and appeared to be a noncompetitive phenomenon relative to glucagon. Maximal NaF-responsive AC did not fall concomitantly with time. Thus, the reduction in glucagon-responsive AC was probably not related to a reduction in the catalytic unit of the enzyme, but could have been due to an alteration in glucagon binding to its receptor sites, or in the coupling mechanism involved in transmission of the hormonal signal to the catalytic unit.", "contents": "Reduced sensitivity of the hepatic adenylate cyclase-cyclic AMP system to glucagon during sustained hormonal stimulation. Hormone-induced desensitization of hormonal regulation of cyclic AMP (cAMP) content has been described in a number of tissues. In the present study, we examined responses of rat liver to glucagon after periods of sustained exposure to the hormone in vivo and in vitro. In intact anesthetized rats infused with glucagon (50 ng/min) for 1 h or more and in liver slices incubated with the hormone (10 muM) for this period, hepatic cAMP responsiveness to glucagon was significantly blunted compared with that of tissue exposed to the hormone for shorter periods. The reduction in hepatic cAMP responsiveness to glucagon appeared to be fully expressed by 2 h. With the doses of hormone employed, the sequential alterations in hepatic responsiveness seemed to be limited to the cAMP system, since other parameters of glucagon action did not wane with time. Diminished hepatic cAMP responsiveness during sustained hormonal exposure could not be attributed to decreased glucagon availability, accelerated extracellular release of cAMP, hepatic ATP depletion, or enhanced phosphodiesterase activity. Studies in vitro suggested that modulation of the cAMP response occurred at the level of adenylate cyclase (AC). During sustained exposure of hepatic slices to glucagon, reductions in glucagon-responsive AC correlated temporally with those in cAMP and both changes were reversible. Alterations in glucagon-responsive AC were demonstrated over a wide range of ATP (10 muM-0.1 mM) and glucagon (10 nM-5 MM) concentrations in the cyclase reaction mixture, and appeared to be a noncompetitive phenomenon relative to glucagon. Maximal NaF-responsive AC did not fall concomitantly with time. Thus, the reduction in glucagon-responsive AC was probably not related to a reduction in the catalytic unit of the enzyme, but could have been due to an alteration in glucagon binding to its receptor sites, or in the coupling mechanism involved in transmission of the hormonal signal to the catalytic unit."} {"id": "PMID:176181", "title": "Activation of adenylate cyclase by cholera toxin in rat liver homogenates.", "content": "The effect of cholera toxin on adenylate cyclase from rat liver has been studied in a broken cell preparation. The activation of the enzyme in this in vitro preparation requires the addition of nicotinamide adenine dinucleotide (NAD) to the incubation medium and the presence of cell components other than the membrane-bound adenylate cyclase. Once the activation of the cyclase is produced, the effect persists despite repeated washing or solubilization of the enzyme. The effect can be obtained with concentrations of cholera toxin as low as 0.4 nM after 15 min of incubation at 22 degrees C, and stimulation can be detected after only 5 min of incubation at 37 degrees C. The activation of the enzyme is still apparent after at least 2 h at 0 degrees C. Preincubation with choleragenoid in vitro does not interfere with this effect of the toxin. Animals pretreated by an intravenous injection of cholera toxin do not respond to the in vitro addition of cholera toxin and NAD to the same extent as untreated animals; i.e., the effects overlap to suggest that the in vitro effect is the same as that in vivo. Responses to isoproterenol, glucagon, and NaF were also similar in the in vitro broken cell-activated system, as previously reported for the enzyme activated in vivo.", "contents": "Activation of adenylate cyclase by cholera toxin in rat liver homogenates. The effect of cholera toxin on adenylate cyclase from rat liver has been studied in a broken cell preparation. The activation of the enzyme in this in vitro preparation requires the addition of nicotinamide adenine dinucleotide (NAD) to the incubation medium and the presence of cell components other than the membrane-bound adenylate cyclase. Once the activation of the cyclase is produced, the effect persists despite repeated washing or solubilization of the enzyme. The effect can be obtained with concentrations of cholera toxin as low as 0.4 nM after 15 min of incubation at 22 degrees C, and stimulation can be detected after only 5 min of incubation at 37 degrees C. The activation of the enzyme is still apparent after at least 2 h at 0 degrees C. Preincubation with choleragenoid in vitro does not interfere with this effect of the toxin. Animals pretreated by an intravenous injection of cholera toxin do not respond to the in vitro addition of cholera toxin and NAD to the same extent as untreated animals; i.e., the effects overlap to suggest that the in vitro effect is the same as that in vivo. Responses to isoproterenol, glucagon, and NaF were also similar in the in vitro broken cell-activated system, as previously reported for the enzyme activated in vivo."} {"id": "PMID:176264", "title": "Cell electrophoresis research directed toward clinical cytodiagnosis.", "content": "The application of cell electrophoresis to cytodiagnosis requires that a scientifically established basis exists for identifying abnormal cells electrophoretically, that research to detect such differences in the cytodiagnostic setting is possible and that a rapid and simple method of cell electrophoresis is adaptable to the clinical setting. Data are presented indicating modifications of electrophoretic mobility due to herpes simplex virus type 1 infection and Rous sarcoma virus transformation of culture cells. A simple apparatus for electrophoretically separating cells on a density gradient and collecting them for subsequent analysis is described, and results of experiments with this apparatus are consistent with those obtained by microscopic electrophoresis. Laser-doppler spectroscopic electrophoresis is suggested as a rapid method adaptable to clinical application.", "contents": "Cell electrophoresis research directed toward clinical cytodiagnosis. The application of cell electrophoresis to cytodiagnosis requires that a scientifically established basis exists for identifying abnormal cells electrophoretically, that research to detect such differences in the cytodiagnostic setting is possible and that a rapid and simple method of cell electrophoresis is adaptable to the clinical setting. Data are presented indicating modifications of electrophoretic mobility due to herpes simplex virus type 1 infection and Rous sarcoma virus transformation of culture cells. A simple apparatus for electrophoretically separating cells on a density gradient and collecting them for subsequent analysis is described, and results of experiments with this apparatus are consistent with those obtained by microscopic electrophoresis. Laser-doppler spectroscopic electrophoresis is suggested as a rapid method adaptable to clinical application."} {"id": "PMID:176265", "title": "Effects of neoplasms on inflammation: depression of macrophage accumulation after tumor implantation.", "content": "The local accumulation of macrophages at sites of neoplasms may be a critical event in immunologically mediated tumor killing. Individuals with neoplasms, however, have been noted to have depressed monocyte chemotactic responsiveness in vitro. To determine the effect of neoplasms on macrophage migration, mice were implanted subcutaneously with either sarcoma or hepatoma cells and their macrophage migratory function quantified in vivo and in vitro. The ability of tumor-bearing animals to mobilize macrophages to an inflammatory site in vivo was depressed by as much as 61% by 6 days after tumor implantation. The in vitro chemotactic responsiveness of macrophages recovered from the peritoneal cavities of tumor-bearing animals was also markedly depressed. Macrophage migration was not affected by implantation of normal syngeneic or allogeneic tissues. In addition, the accumulation of polymorphonuclear leukocytes in vivo was not depressed in tumor-bearing animals. These findings suggest that neoplasms themselves may depress the host's ability to localize macrophages at inflammatory sites in vivo and thereby hinder immunologically mediated tumor destruction.", "contents": "Effects of neoplasms on inflammation: depression of macrophage accumulation after tumor implantation. The local accumulation of macrophages at sites of neoplasms may be a critical event in immunologically mediated tumor killing. Individuals with neoplasms, however, have been noted to have depressed monocyte chemotactic responsiveness in vitro. To determine the effect of neoplasms on macrophage migration, mice were implanted subcutaneously with either sarcoma or hepatoma cells and their macrophage migratory function quantified in vivo and in vitro. The ability of tumor-bearing animals to mobilize macrophages to an inflammatory site in vivo was depressed by as much as 61% by 6 days after tumor implantation. The in vitro chemotactic responsiveness of macrophages recovered from the peritoneal cavities of tumor-bearing animals was also markedly depressed. Macrophage migration was not affected by implantation of normal syngeneic or allogeneic tissues. In addition, the accumulation of polymorphonuclear leukocytes in vivo was not depressed in tumor-bearing animals. These findings suggest that neoplasms themselves may depress the host's ability to localize macrophages at inflammatory sites in vivo and thereby hinder immunologically mediated tumor destruction."} {"id": "PMID:176266", "title": "Antibody in the sera of tumor-bearing mice that mediates spleen cell cytotoxicity toward the autologous tumor.", "content": "Pretreatment of MTV-induced BALB/cfC3H mammary tumor cells with autologous serum results in increased spleen cell cytotoxic activity and the recruitment of previously inactive spleen cells to cytotoxic activity against the target cells. These recruiting antibodies are tumor-specific for individual tumors; pretreatment with such serum of target cells of an MTV-induced mammary tumor obtained from a different BALB/cfC3H female results in blocking of spleen cell activity. The autologous recruiting factors are active at dilutions of 1000 or more of whole serum are found in the 19S fraction after gel filtration.", "contents": "Antibody in the sera of tumor-bearing mice that mediates spleen cell cytotoxicity toward the autologous tumor. Pretreatment of MTV-induced BALB/cfC3H mammary tumor cells with autologous serum results in increased spleen cell cytotoxic activity and the recruitment of previously inactive spleen cells to cytotoxic activity against the target cells. These recruiting antibodies are tumor-specific for individual tumors; pretreatment with such serum of target cells of an MTV-induced mammary tumor obtained from a different BALB/cfC3H female results in blocking of spleen cell activity. The autologous recruiting factors are active at dilutions of 1000 or more of whole serum are found in the 19S fraction after gel filtration."} {"id": "PMID:176267", "title": "Complexity of factors in sera of different mice that affect MTV-induced mammary tumor cells.", "content": "Specific spleen cell activity in microcytotoxicity assay can be altered by pretreatment of target mammary tumor virus (MTV)-induced mammary tumor cells with serum. Serum from both BALB/cfC3H females neonatally infected with MTV and BALB/c females horizontally exposed to MTV antigens will block specific spleen cell activity against isologous mammary tumor cells. On fractionation of sera, blocking factors are localized in the 7s fraction. The 19s fraction contains recruiting factors that are not detectable in the unfractionated serum; these factors are active against isologous tumors and are thus distinct from the tumor-specific recruiting factors previously described in the sera of tumor-bearing females, which are active only against the autologous tumor. Antibodies mediating complement-dependent cell lysis are also detectable after serum fractionation.", "contents": "Complexity of factors in sera of different mice that affect MTV-induced mammary tumor cells. Specific spleen cell activity in microcytotoxicity assay can be altered by pretreatment of target mammary tumor virus (MTV)-induced mammary tumor cells with serum. Serum from both BALB/cfC3H females neonatally infected with MTV and BALB/c females horizontally exposed to MTV antigens will block specific spleen cell activity against isologous mammary tumor cells. On fractionation of sera, blocking factors are localized in the 7s fraction. The 19s fraction contains recruiting factors that are not detectable in the unfractionated serum; these factors are active against isologous tumors and are thus distinct from the tumor-specific recruiting factors previously described in the sera of tumor-bearing females, which are active only against the autologous tumor. Antibodies mediating complement-dependent cell lysis are also detectable after serum fractionation."} {"id": "PMID:176268", "title": "Inhibition of mitogen-induced lymphocyte transformation by local anesthetics.", "content": "Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanvalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10(-6)M and concentrations of lidocaine greater than 2 x 10(-3)M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or 51Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calciunown membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganized cell membranes so as to interfere with the surface membrane elaboration or action of a second messenger, or interfere with cell-cell interactions.", "contents": "Inhibition of mitogen-induced lymphocyte transformation by local anesthetics. Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanvalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10(-6)M and concentrations of lidocaine greater than 2 x 10(-3)M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or 51Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calciunown membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganized cell membranes so as to interfere with the surface membrane elaboration or action of a second messenger, or interfere with cell-cell interactions."} {"id": "PMID:176269", "title": "Immunity to C-type RNA viruses: antibody formation after natural or deliberate infection.", "content": "A combined virologic and immunologic study was done in mice that were either naturally or deliberately infected with C-type RNA viruses. In about 60% of B10. A mice, natural infection was accompanied by detectable anti-VEA antibodies in the serum. The absence of such antibodies was a reliable indicator of the absence of virus in B10 mice. Deliberately infected young adult B10 mice failed to eliminate the virus completely, despite high titers of anti-VEA antibodies. B10 mice exposed to B tropic viruses at birth made anti-VEA antibodies but failed to eliminate the virus. By contrast, some NIH Swiss mice exposed to N-tropic virus at birth made anti-VEA antibodies and eliminated the virus.", "contents": "Immunity to C-type RNA viruses: antibody formation after natural or deliberate infection. A combined virologic and immunologic study was done in mice that were either naturally or deliberately infected with C-type RNA viruses. In about 60% of B10. A mice, natural infection was accompanied by detectable anti-VEA antibodies in the serum. The absence of such antibodies was a reliable indicator of the absence of virus in B10 mice. Deliberately infected young adult B10 mice failed to eliminate the virus completely, despite high titers of anti-VEA antibodies. B10 mice exposed to B tropic viruses at birth made anti-VEA antibodies but failed to eliminate the virus. By contrast, some NIH Swiss mice exposed to N-tropic virus at birth made anti-VEA antibodies and eliminated the virus."} {"id": "PMID:176270", "title": "Lysis of tumor cells by antibody and complement. VI. Enhanced killing of enzyme-pretreated tumor cells.", "content": "The ascites form of a chemically induced guinea pig hepatoma, line-10, was resistant to killing in vitro by xenogeneic antibody and guinea pig complement. Pretreatment of line-10 cells with certain proteolytic enzymes rendered tham susceptible to the killing action of antibody and guinea pig complement. The effects of enzyme pretreatment were dependent on enzyme concentration, temperature, and could be blocked by addition of competitive or non-competitive inhibitors. The effect of the enzyme treatment could reversed by incubating the treated cells at 37 degrees C (but not at 0 degrees C), in the absence of the enzyme. Effective enzymes included ficin, bromelain, pronase, elastase, papain, trypsin, collagenase, lipases type I and type VI, and the neuraminidase preparation isolated from Clostridium perfringens. The activity of the lipase preparations and the neuraminidase preparation isolated from Clostridium perfringens appeared to be caused by proteolytic enzyme contamination. Enzyme preparations that proved ineffecitve in rendering the line-10 cells sensitive to killing by antibody and guinea pig complement included DNase, RNase, beta-glucuronidase type 6A or type B10, hyaluronidase type V or type VI, and pectinesterase.", "contents": "Lysis of tumor cells by antibody and complement. VI. Enhanced killing of enzyme-pretreated tumor cells. The ascites form of a chemically induced guinea pig hepatoma, line-10, was resistant to killing in vitro by xenogeneic antibody and guinea pig complement. Pretreatment of line-10 cells with certain proteolytic enzymes rendered tham susceptible to the killing action of antibody and guinea pig complement. The effects of enzyme pretreatment were dependent on enzyme concentration, temperature, and could be blocked by addition of competitive or non-competitive inhibitors. The effect of the enzyme treatment could reversed by incubating the treated cells at 37 degrees C (but not at 0 degrees C), in the absence of the enzyme. Effective enzymes included ficin, bromelain, pronase, elastase, papain, trypsin, collagenase, lipases type I and type VI, and the neuraminidase preparation isolated from Clostridium perfringens. The activity of the lipase preparations and the neuraminidase preparation isolated from Clostridium perfringens appeared to be caused by proteolytic enzyme contamination. Enzyme preparations that proved ineffecitve in rendering the line-10 cells sensitive to killing by antibody and guinea pig complement included DNase, RNase, beta-glucuronidase type 6A or type B10, hyaluronidase type V or type VI, and pectinesterase."} {"id": "PMID:176271", "title": "Effect of lectins on the levels of cAMP and cGMP in guinea pig lymphocytes: early responses of lymph node cells to mitogenic and non-mitogenic lectins.", "content": "Guinea pig lymph node lymphocytes were reacted with two mitogenic lectins (LcL-A or PHA) and two nonmitogenic lectins (AbL or WGA)m and the levels of cAMP and cGMP were determined during 30 min of culture. Various concentrations of LcL-A and PHA caused modest (1.5 to 2-fold) rises in cAMP levels. However, the rise in cAMP did not correlate with the degree of mitogenicity. AbL caused a greater rise in cAMP than the mitogenic lectins whereas WGA had no effect on cAMP levels. None of the four lectins causes an appreciable (i.e., greater than 1.5-fold) change in cGMP levels. There does not seem to be any positive correlation between early changes of cAMP and/or cGMP and mitogenesis.", "contents": "Effect of lectins on the levels of cAMP and cGMP in guinea pig lymphocytes: early responses of lymph node cells to mitogenic and non-mitogenic lectins. Guinea pig lymph node lymphocytes were reacted with two mitogenic lectins (LcL-A or PHA) and two nonmitogenic lectins (AbL or WGA)m and the levels of cAMP and cGMP were determined during 30 min of culture. Various concentrations of LcL-A and PHA caused modest (1.5 to 2-fold) rises in cAMP levels. However, the rise in cAMP did not correlate with the degree of mitogenicity. AbL caused a greater rise in cAMP than the mitogenic lectins whereas WGA had no effect on cAMP levels. None of the four lectins causes an appreciable (i.e., greater than 1.5-fold) change in cGMP levels. There does not seem to be any positive correlation between early changes of cAMP and/or cGMP and mitogenesis."} {"id": "PMID:176272", "title": "An IgG-Fc receptor induced in cytomegalovirus-infected human fibroblasts.", "content": "Cytomegalovirus- (CMV) infected cultured human fibroblasts incubated with normal human serum were shown to react with IgG by direct and indirect fluorescent antibody tests. The binding of IgG to infected cells was unrelated to the presence of anti-CMV complement fixing (CF) antibodies and was not observed with uninfected cells. The reaction was first observed 36 hours after infection as diffuse cytoplasmic staining which by 72 hr became localized into a dense perinuclear structure. The cytoplasmic fluorescence was not detected with anti-IgA or anti-IgM fluorescent conjugates. The reaction was seen with purified IgG and Fc fragments but was only minimally detectable with Fab fragments. It occurred in fibroblasts infected with three standard laboratory strains of CMV and seven recent CMV isolates from patients and was observed in six separate lots of human foreskin fibroblast cultures as well as in WI-38 cells. We conclude that CMV infection induces the formation of a IgG receptor in human fibroblasts.", "contents": "An IgG-Fc receptor induced in cytomegalovirus-infected human fibroblasts. Cytomegalovirus- (CMV) infected cultured human fibroblasts incubated with normal human serum were shown to react with IgG by direct and indirect fluorescent antibody tests. The binding of IgG to infected cells was unrelated to the presence of anti-CMV complement fixing (CF) antibodies and was not observed with uninfected cells. The reaction was first observed 36 hours after infection as diffuse cytoplasmic staining which by 72 hr became localized into a dense perinuclear structure. The cytoplasmic fluorescence was not detected with anti-IgA or anti-IgM fluorescent conjugates. The reaction was seen with purified IgG and Fc fragments but was only minimally detectable with Fab fragments. It occurred in fibroblasts infected with three standard laboratory strains of CMV and seven recent CMV isolates from patients and was observed in six separate lots of human foreskin fibroblast cultures as well as in WI-38 cells. We conclude that CMV infection induces the formation of a IgG receptor in human fibroblasts."} {"id": "PMID:176273", "title": "Release of xenotropic type C RNA virus in response to lipopolysaccharide: acitivity of lipid-A portion upon B lymphocytes.", "content": "The present studies demonstrate that lipopolysaccharide (LPS) causes the release of endogenous xenotropic type-C RNA virus from BALB/c spleen cells. The evidence suggests that virus release is stimulated by the lipid-A portion of LPS and primarily involves an action of LPS on B lymphocytes. LPS had little or no effect on virus release by T lymphocytes, macrophages, or fibroblasts. These results indicate that the differentiated state of the cell plays an important role in the regulation of endogenous virus release.", "contents": "Release of xenotropic type C RNA virus in response to lipopolysaccharide: acitivity of lipid-A portion upon B lymphocytes. The present studies demonstrate that lipopolysaccharide (LPS) causes the release of endogenous xenotropic type-C RNA virus from BALB/c spleen cells. The evidence suggests that virus release is stimulated by the lipid-A portion of LPS and primarily involves an action of LPS on B lymphocytes. LPS had little or no effect on virus release by T lymphocytes, macrophages, or fibroblasts. These results indicate that the differentiated state of the cell plays an important role in the regulation of endogenous virus release."} {"id": "PMID:176274", "title": "Mitogen induction of murine C-type viruses. I. Analysis of lymphoid cell subpopulations.", "content": "We reported previously in vitro induction of endogenous C-type viruses from normal mouse spleen cells by lipopolysaccharide (LPS) as well as by combination treatment with concanabalin A and 5-bromo-2'-deoxyuridine (Con A/BrdU). To identify the cell types sensitive to virus induction and to study the relationship of mitogenicity to virus induction we have compared T cell populations (BALB/c thymus cells and cortisone-resistant thymus cells), B cell populations (nu/nu spleen cells and lymph node cells), adherent BALB/c peritoneal cells and mixed populations (BALB/c spleen cells, macrophage-depleted BALB/c spleen cells, and lymph node cells). LPS-induction occurred only in B cell-containing populations. In contrast, induction by Con A/BrdU depended on the presence of both T and B cells. In both instances, neither macrophages nor hemopoietic cells appeared to be a major source of virus. Treatment with anti-Ig serum and complement reduced virus induction by LPS/BrdU but not by Con A/BrdU suggesting that different cell populations produce virus after stimulation with these two different mitogens.", "contents": "Mitogen induction of murine C-type viruses. I. Analysis of lymphoid cell subpopulations. We reported previously in vitro induction of endogenous C-type viruses from normal mouse spleen cells by lipopolysaccharide (LPS) as well as by combination treatment with concanabalin A and 5-bromo-2'-deoxyuridine (Con A/BrdU). To identify the cell types sensitive to virus induction and to study the relationship of mitogenicity to virus induction we have compared T cell populations (BALB/c thymus cells and cortisone-resistant thymus cells), B cell populations (nu/nu spleen cells and lymph node cells), adherent BALB/c peritoneal cells and mixed populations (BALB/c spleen cells, macrophage-depleted BALB/c spleen cells, and lymph node cells). LPS-induction occurred only in B cell-containing populations. In contrast, induction by Con A/BrdU depended on the presence of both T and B cells. In both instances, neither macrophages nor hemopoietic cells appeared to be a major source of virus. Treatment with anti-Ig serum and complement reduced virus induction by LPS/BrdU but not by Con A/BrdU suggesting that different cell populations produce virus after stimulation with these two different mitogens."} {"id": "PMID:176275", "title": "Effect of cross-immunization on monotypic antibody responses to herpes simplex virus types 1 and 2.", "content": "New Zealand White rabbits were immunized subcutaneously with partially purified UV-inactivated preparations of herpes simplex virus (HSV-1 or HSV-2) in complete Freund's adjuvant. After the initial immunizations, designated groups of animals received additional amounts of either HSV-1 or HSV-2 at 35-day intervals. Sera were absorbed with lysates of cells infected with heterotypic virus and the residual monotypic antibodies were detected by 51Cr-release assay using HSV-infected target cells. A positive correlation was found between the ratio of neutralizing antibodies to HSV-1 and HSV-2 (II/I index) and the content of monotypic antibodies. Results showed that production of monotypic antibodies to HSV-1 And HSV-2, under the conditions employed, was independent of previous exposure to HSV.", "contents": "Effect of cross-immunization on monotypic antibody responses to herpes simplex virus types 1 and 2. New Zealand White rabbits were immunized subcutaneously with partially purified UV-inactivated preparations of herpes simplex virus (HSV-1 or HSV-2) in complete Freund's adjuvant. After the initial immunizations, designated groups of animals received additional amounts of either HSV-1 or HSV-2 at 35-day intervals. Sera were absorbed with lysates of cells infected with heterotypic virus and the residual monotypic antibodies were detected by 51Cr-release assay using HSV-infected target cells. A positive correlation was found between the ratio of neutralizing antibodies to HSV-1 and HSV-2 (II/I index) and the content of monotypic antibodies. Results showed that production of monotypic antibodies to HSV-1 And HSV-2, under the conditions employed, was independent of previous exposure to HSV."} {"id": "PMID:176278", "title": "The seroepidemiology of reovirus, coxsackievirus infections among Panamanian Indian children.", "content": "Rates of hepatitis B virus infection varied significantly among Panamanian Indian tribes. Choc\u00f3 and Mainland Cuna Indians had a greater prevalence of antibody to hepatitis B surface antigen than Guaymi and Island Cuna Indians. The village water supply appeared to be the major environmental difference that distinguished the tribes from one another. Since contaminated water plays a role in the transmission of enterovirus, an attempt was made to assess relative exposure to contaminated water by determination of the prevalence of antibodies to reovirus and coxsackievirus B in children 10 years old or younger. Infection with coxsackievirus B occurred more frequently in Choc\u00f3 and Mainland Cuna Indians than in Guaymi or Island Cuna Indians. Although essentially all children tested were exposed to reoviruses, Mainland Cuna Indians had the highest geometric mean titers of antibody, followed by Choc\u00f3, Guaymi, and Island Cuna Indians in descending order. This parallel in rates of hepatitis B and enterovirus infection supports the hypothesis that fecal-oral transmission of hepatitis B virus is important in certain populations.", "contents": "The seroepidemiology of reovirus, coxsackievirus infections among Panamanian Indian children. Rates of hepatitis B virus infection varied significantly among Panamanian Indian tribes. Choc\u00f3 and Mainland Cuna Indians had a greater prevalence of antibody to hepatitis B surface antigen than Guaymi and Island Cuna Indians. The village water supply appeared to be the major environmental difference that distinguished the tribes from one another. Since contaminated water plays a role in the transmission of enterovirus, an attempt was made to assess relative exposure to contaminated water by determination of the prevalence of antibodies to reovirus and coxsackievirus B in children 10 years old or younger. Infection with coxsackievirus B occurred more frequently in Choc\u00f3 and Mainland Cuna Indians than in Guaymi or Island Cuna Indians. Although essentially all children tested were exposed to reoviruses, Mainland Cuna Indians had the highest geometric mean titers of antibody, followed by Choc\u00f3, Guaymi, and Island Cuna Indians in descending order. This parallel in rates of hepatitis B and enterovirus infection supports the hypothesis that fecal-oral transmission of hepatitis B virus is important in certain populations."} {"id": "PMID:176279", "title": "Mechanism of activation adenylate cyclase in vitro by polymyxin-released, heat-labile enterotoxin of Escherichia coli.", "content": "Heat-labile enterotoxic material released from Escherichia coli by polymyxin B activates the adenylate cyclase of pigeon erythrocyte ghosts in a time- and concentration-dependent manner. The activation requires nicotinamide adenine dinucleotide, adenosine triphosphate, and another component of the erythrocyte supernatant. The active species has a molecular weight of about 23,000-24,000 daltons, is inhibited by antibodies to the toxin of Vibrio cholerae, and is not irreversibly denatured by sodium dodecyl sulfate. Thus in many respects the active species from E. coli behaves the same as peptide A1 of cholera toxin.", "contents": "Mechanism of activation adenylate cyclase in vitro by polymyxin-released, heat-labile enterotoxin of Escherichia coli. Heat-labile enterotoxic material released from Escherichia coli by polymyxin B activates the adenylate cyclase of pigeon erythrocyte ghosts in a time- and concentration-dependent manner. The activation requires nicotinamide adenine dinucleotide, adenosine triphosphate, and another component of the erythrocyte supernatant. The active species has a molecular weight of about 23,000-24,000 daltons, is inhibited by antibodies to the toxin of Vibrio cholerae, and is not irreversibly denatured by sodium dodecyl sulfate. Thus in many respects the active species from E. coli behaves the same as peptide A1 of cholera toxin."} {"id": "PMID:176280", "title": "Mode of action of Vibrio cholerae enterotoxin in cultured adrenal tumor cells.", "content": "The effects of Vibrio cholerae enterotoxin on steroidogenesis and on formation of adenosine 3':5'-cyclic phosphate (cyclic AMP) in two adrenal tumor cell lines were compared. Steroidogenesis was half-maximal at concentrations of 1 ng of cholera toxin/ml in the mutant OS-3 cells and 3 ng of cholera toxin/ml in the parent Y-1 cells. At the end of an 8-hr incubation, toxin-induced formation of cyclic AMP in the mutant cell line was reduced by 90%. A molar ratio of GM1 ganglioside (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide; GGnSLC) to cholera toxin of 3:1 caused half-maximal inhibition of steroidogenesis in both cell lines. When equine antiserum to choleragenoid was added to adrenal cells 15 min after cholera toxin, there was marked inhibition of cyclic AMP formation and of steroidogenesis. Pretreatment of Y-1 cells with adrenocorticotropin rendered them unresponsive to hormonal induction of cyclic AMP formation, but these cells had an unimpaired response to cholera toxin. These studies, utilizing two adrenal cell lines, suggest important differences between the mode of action of cholera toxin and that of adrenocorticotropin in cultured adrenal tumor cells.", "contents": "Mode of action of Vibrio cholerae enterotoxin in cultured adrenal tumor cells. The effects of Vibrio cholerae enterotoxin on steroidogenesis and on formation of adenosine 3':5'-cyclic phosphate (cyclic AMP) in two adrenal tumor cell lines were compared. Steroidogenesis was half-maximal at concentrations of 1 ng of cholera toxin/ml in the mutant OS-3 cells and 3 ng of cholera toxin/ml in the parent Y-1 cells. At the end of an 8-hr incubation, toxin-induced formation of cyclic AMP in the mutant cell line was reduced by 90%. A molar ratio of GM1 ganglioside (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide; GGnSLC) to cholera toxin of 3:1 caused half-maximal inhibition of steroidogenesis in both cell lines. When equine antiserum to choleragenoid was added to adrenal cells 15 min after cholera toxin, there was marked inhibition of cyclic AMP formation and of steroidogenesis. Pretreatment of Y-1 cells with adrenocorticotropin rendered them unresponsive to hormonal induction of cyclic AMP formation, but these cells had an unimpaired response to cholera toxin. These studies, utilizing two adrenal cell lines, suggest important differences between the mode of action of cholera toxin and that of adrenocorticotropin in cultured adrenal tumor cells."} {"id": "PMID:176281", "title": "Multiple roles of erythrocyte supernatant in the activation of adenylate cyclase by Vibrio cholerae toxin in vitro.", "content": "Peptide A1 of Vibrio cholerae toxin, nicotinamide adenine dinucleotide, adenosine triphosphate, and a soluble protein present in erythrocyte supernatant are required for the activation of pigeon erythrocyte ghost adenylate cyclase but are not required to maintain the activated state. The compounds are all required simultaneously, and when all are added to ghosts, adenylate cyclase activity increases at a linear rate without delay. Under optimal conditions significant activation of cyclase is given by less than one molecule of toxin per ghost. Intact cholera toxin may be inactive in vitro. There is a delay of about 1 min between the addition of intact toxin and the attainment of the final rate of increase of adenylate cyclase activity. During this period, glutathione reduces the disulfide bond between peptides A1 and A2. The delay is eliminated if the toxin is reduced before addition. More A1 is liberated if the toxin is also denatured with sodium dodecyl sulfate.", "contents": "Multiple roles of erythrocyte supernatant in the activation of adenylate cyclase by Vibrio cholerae toxin in vitro. Peptide A1 of Vibrio cholerae toxin, nicotinamide adenine dinucleotide, adenosine triphosphate, and a soluble protein present in erythrocyte supernatant are required for the activation of pigeon erythrocyte ghost adenylate cyclase but are not required to maintain the activated state. The compounds are all required simultaneously, and when all are added to ghosts, adenylate cyclase activity increases at a linear rate without delay. Under optimal conditions significant activation of cyclase is given by less than one molecule of toxin per ghost. Intact cholera toxin may be inactive in vitro. There is a delay of about 1 min between the addition of intact toxin and the attainment of the final rate of increase of adenylate cyclase activity. During this period, glutathione reduces the disulfide bond between peptides A1 and A2. The delay is eliminated if the toxin is reduced before addition. More A1 is liberated if the toxin is also denatured with sodium dodecyl sulfate."} {"id": "PMID:176282", "title": "Cholera toxin and the adenylate cyclase-activating signal.", "content": "Studies with chemically modified cholera toxin derivatives showed that all treatments that decreased the ability of toxin to bind to mouse thymus cells or to polystyrene-coupled GM1 ganglioside caused a concomitant reduction in the toxin's ability to increase adenosine 3':5'-cyclic phosphate (cyclic AMP) in thymus cells and skin vascular permeability in rabbits. Dissociation of the H (heavy) and L (light) subunits abolished the biologic activity without inhibiting receptor binding, as did treatment with arginyl-specific reagents (which did not change the aggregation state of the toxin). When thymus cells were incubated with 125I-labelled toxin at 37C,only about 1% of the total cell-bound radioactivity was recovered in the cytosol supernate. Similar values were found for cells incubated with toxin at 0C, and with 125I-labelled choleragenoid at 37C or 0C. Thymus cells rapidly bound less than or equal to equal to 5 X 10(4) cholera toxin molecules per cell at both 0C and 37C. Much less, however, of the radioactive toxin bound at 37C than of that bound at 0C was displaced by addition of unlabelled toxin or choleragenoid. Similar temperature-related irreversible binding was noted with 125I-labelled choleragenoid. The relative amounts of H and L subunits in the irreversibly cell-bound and in the displaced 125I-labelled toxin were indistinguishable. Treatment of thymus cells at 37C, but not at 0C, with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide caused a 10-fold reduction of adenylate cyclase stimulation by cholera toxin without inhibiting activation by epinephrine or prostaglandin E1, or appreciably altering the basal, unstimulated enzyme activity. The carbodiimide inhibited the cyclic AMP response to cholera toxin when added shortly after the toxin had bound to the cells (early in the lag phase).", "contents": "Cholera toxin and the adenylate cyclase-activating signal. Studies with chemically modified cholera toxin derivatives showed that all treatments that decreased the ability of toxin to bind to mouse thymus cells or to polystyrene-coupled GM1 ganglioside caused a concomitant reduction in the toxin's ability to increase adenosine 3':5'-cyclic phosphate (cyclic AMP) in thymus cells and skin vascular permeability in rabbits. Dissociation of the H (heavy) and L (light) subunits abolished the biologic activity without inhibiting receptor binding, as did treatment with arginyl-specific reagents (which did not change the aggregation state of the toxin). When thymus cells were incubated with 125I-labelled toxin at 37C,only about 1% of the total cell-bound radioactivity was recovered in the cytosol supernate. Similar values were found for cells incubated with toxin at 0C, and with 125I-labelled choleragenoid at 37C or 0C. Thymus cells rapidly bound less than or equal to equal to 5 X 10(4) cholera toxin molecules per cell at both 0C and 37C. Much less, however, of the radioactive toxin bound at 37C than of that bound at 0C was displaced by addition of unlabelled toxin or choleragenoid. Similar temperature-related irreversible binding was noted with 125I-labelled choleragenoid. The relative amounts of H and L subunits in the irreversibly cell-bound and in the displaced 125I-labelled toxin were indistinguishable. Treatment of thymus cells at 37C, but not at 0C, with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide caused a 10-fold reduction of adenylate cyclase stimulation by cholera toxin without inhibiting activation by epinephrine or prostaglandin E1, or appreciably altering the basal, unstimulated enzyme activity. The carbodiimide inhibited the cyclic AMP response to cholera toxin when added shortly after the toxin had bound to the cells (early in the lag phase)."} {"id": "PMID:176283", "title": "Interaction of Vibrio cholerae toxin with sarcoma 180 cell membranes.", "content": "Three discrete phases are discernible in the activation, by Vibrio cholerae toxin, of adenylate cyclase in fragments of sarcoma 180 cell membranes. In the first, or preparatory, phase the toxin must be exposed to dithiothreitol or nicotinamide adenine dinucleotide (NAD) in the absence of the membranes. In the second phase, the prepared toxin is dissociated to yield a macromolecular cyclase-activating factor (MCAF) in the presence of the membranes. In the third phase, membrane basal adenylate cyclase is activated by MCAF in the presence of NAD. The integrity of the catecholamine or beta-receptor associated with sarcoma adenylate cyclase is irrelevant in the activation of cyclase by MCAF. This activation proceeds undiminished even if the beta-receptor is desensitized or blocked by propranolol.", "contents": "Interaction of Vibrio cholerae toxin with sarcoma 180 cell membranes. Three discrete phases are discernible in the activation, by Vibrio cholerae toxin, of adenylate cyclase in fragments of sarcoma 180 cell membranes. In the first, or preparatory, phase the toxin must be exposed to dithiothreitol or nicotinamide adenine dinucleotide (NAD) in the absence of the membranes. In the second phase, the prepared toxin is dissociated to yield a macromolecular cyclase-activating factor (MCAF) in the presence of the membranes. In the third phase, membrane basal adenylate cyclase is activated by MCAF in the presence of NAD. The integrity of the catecholamine or beta-receptor associated with sarcoma adenylate cyclase is irrelevant in the activation of cyclase by MCAF. This activation proceeds undiminished even if the beta-receptor is desensitized or blocked by propranolol."} {"id": "PMID:176284", "title": "Purification of the polymyxin-released, heat-labile enterotoxin of Escherichia coli.", "content": "The heat-labile enterotoxin of Escherichia coli strain H-10407 has been purified by use of a commercially available affinity gel (Affi-Gel 202). This gel possesses a strong and highly specific affinity for the enterotoxin released from intact E. coli cells by polymyxin B. The polymyxin-release technique could be used with fermenter-size batches of E. coli cells grown in a casamino acids-yeast extract medium. With a simple (NH4)2SO4 back-extraction step prior to affinity chromatography, large batches of E. coli enterotoxin could be processed rapidly. Affi-Gel 202-purified E. coli enterotoxin produced a single precipitin band in the presence of several different antisera against crude preparations of the toxin. The same antigen produced a precipitin band in the presence of both cholera antitoxin and antiserum to choleragenoid.", "contents": "Purification of the polymyxin-released, heat-labile enterotoxin of Escherichia coli. The heat-labile enterotoxin of Escherichia coli strain H-10407 has been purified by use of a commercially available affinity gel (Affi-Gel 202). This gel possesses a strong and highly specific affinity for the enterotoxin released from intact E. coli cells by polymyxin B. The polymyxin-release technique could be used with fermenter-size batches of E. coli cells grown in a casamino acids-yeast extract medium. With a simple (NH4)2SO4 back-extraction step prior to affinity chromatography, large batches of E. coli enterotoxin could be processed rapidly. Affi-Gel 202-purified E. coli enterotoxin produced a single precipitin band in the presence of several different antisera against crude preparations of the toxin. The same antigen produced a precipitin band in the presence of both cholera antitoxin and antiserum to choleragenoid."} {"id": "PMID:176287", "title": "Malignant oncocytic tumour of the parotid salivary gland.", "content": "A 49-year-old man developed a tumour mass in his right parotid salivary gland nine years after a histologically proven benign mixed tumour of the same salivary gland had been surgically removed. Radical resection of the right parotid salivary gland and associated lymph nodes and soft tissues of the neck was performed. The parotid tumour was composed of oncocytic cells which infiltrated the surviving salivary gland tissue. Most of the excised lymph nodes contained metastatic deposits of oncocytic cells identical to the tumour seen in the parotid. There are no previous reports of the occurrence of both pleomorphic adenoma and malignant oncocytoma in the same salivary gland.", "contents": "Malignant oncocytic tumour of the parotid salivary gland. A 49-year-old man developed a tumour mass in his right parotid salivary gland nine years after a histologically proven benign mixed tumour of the same salivary gland had been surgically removed. Radical resection of the right parotid salivary gland and associated lymph nodes and soft tissues of the neck was performed. The parotid tumour was composed of oncocytic cells which infiltrated the surviving salivary gland tissue. Most of the excised lymph nodes contained metastatic deposits of oncocytic cells identical to the tumour seen in the parotid. There are no previous reports of the occurrence of both pleomorphic adenoma and malignant oncocytoma in the same salivary gland."} {"id": "PMID:176288", "title": "Unilateral multiple tumours of the parotid gland.", "content": "The occurrence of two morphologically distinct tumors in a single parotid gland is rare. Pathologic examination of a unilateral parotid mass removed from a 63-year-old male revealed the presence of a benign mixed tumor and an adenolymphoma. No other examples of this relationship were encountered in the literature.", "contents": "Unilateral multiple tumours of the parotid gland. The occurrence of two morphologically distinct tumors in a single parotid gland is rare. Pathologic examination of a unilateral parotid mass removed from a 63-year-old male revealed the presence of a benign mixed tumor and an adenolymphoma. No other examples of this relationship were encountered in the literature."} {"id": "PMID:176289", "title": "Measurement of apolipoprotein A-I in rat high density lipoprotein and in rat plasma by radioimmunoassay.", "content": "A double antibody radioimmunoassay (RIA) for rat apolipoprotein A-I is reported. The ApoA-I isolated from delipidated HDL by gel filtration yielded a single band on polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS), and its amino acid composition resembled that reported by others. ApoA-I was iodinated by lactoperoxidase and the resulting 125I-apoA-I was purified by gel filtration. Up to 93% of 125I-apoA-I was precipitable by antibody and greater than 99% of bound 125I-apoA-I was displaced by \"cold\" apoA-I. Other rat lopoproteins and apolipoproteins did not react in this system. Human plasma were also not reactive, nor were dog, goat, and sheep plasmas.", "contents": "Measurement of apolipoprotein A-I in rat high density lipoprotein and in rat plasma by radioimmunoassay. A double antibody radioimmunoassay (RIA) for rat apolipoprotein A-I is reported. The ApoA-I isolated from delipidated HDL by gel filtration yielded a single band on polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS), and its amino acid composition resembled that reported by others. ApoA-I was iodinated by lactoperoxidase and the resulting 125I-apoA-I was purified by gel filtration. Up to 93% of 125I-apoA-I was precipitable by antibody and greater than 99% of bound 125I-apoA-I was displaced by \"cold\" apoA-I. Other rat lopoproteins and apolipoproteins did not react in this system. Human plasma were also not reactive, nor were dog, goat, and sheep plasmas."} {"id": "PMID:176290", "title": "Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver.", "content": "The apoproteins of serum lipoproteins and of lipoproteins present in a nonrecirculating perfusate of rat liver were compared by immunochemical, gel electrophoretic, and solubility techniques. Serum and perfusate very low density lipoprotein apoprotein composition were not different. No evidence for the presence of a lipoprotein resembling serum low density lipoprotein was obtained. However, the apoprotein composition of circulatory high density lipoprotein was quantitatively different from the secretory product in the density 1.06-1.21 range. As measured by stained sodium dodecyl sulfate gel electrophoretic patterns, the arginine-rich protein was the major secretory apoprotein while the A-I protein was the major apoprotein in circulating high density lipoprotein. A very similar pattern was seen in perfusates of orotic acid-fatty livers. It was concluded that although the liver secrets lipoproteins in the high density class, circulatory high density lipoprotein is largely a product of catabolic processes.", "contents": "Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver. The apoproteins of serum lipoproteins and of lipoproteins present in a nonrecirculating perfusate of rat liver were compared by immunochemical, gel electrophoretic, and solubility techniques. Serum and perfusate very low density lipoprotein apoprotein composition were not different. No evidence for the presence of a lipoprotein resembling serum low density lipoprotein was obtained. However, the apoprotein composition of circulatory high density lipoprotein was quantitatively different from the secretory product in the density 1.06-1.21 range. As measured by stained sodium dodecyl sulfate gel electrophoretic patterns, the arginine-rich protein was the major secretory apoprotein while the A-I protein was the major apoprotein in circulating high density lipoprotein. A very similar pattern was seen in perfusates of orotic acid-fatty livers. It was concluded that although the liver secrets lipoproteins in the high density class, circulatory high density lipoprotein is largely a product of catabolic processes."} {"id": "PMID:176291", "title": "Competitive protein binding radioassay of plasma and urinary unconjugated cortisol.", "content": "In order to establish a more reliable profile of the function of the adrenal cortex, a study has been made of this simultaneous estimation of plasma and urinary unconjugated cortisol by competitive protein binding (CPB) radioassay. Both plasma and urinary cortisol were measured by CPB radioassay after solvent extraction. Normal ranges were found for plasma and urinary cortisol. The samples obtained in the morning (8:00 am) established a normal plasma cortisol range of 9.0-21.6 mug% with a mean of 15.3. range for urinary unconjugated cortisol was 12.0-41.5 mug/day (mean 26.9). Dexamethasone suppression and adrenocorticotrophic hormone stimulation of plasma and urinary cortisol were tested with individuals having normal and abnormal adrenal cortical function. RESULTS INDICATED A GOOD CLINICOPATHOLOGICAL CORRELATION. It was concluded that plasma and urinary unconjugated cortisol are reliable laboratory tests for adrenocortical function and would be the methods of choice rather than urinary 17-ketogenic steroids.", "contents": "Competitive protein binding radioassay of plasma and urinary unconjugated cortisol. In order to establish a more reliable profile of the function of the adrenal cortex, a study has been made of this simultaneous estimation of plasma and urinary unconjugated cortisol by competitive protein binding (CPB) radioassay. Both plasma and urinary cortisol were measured by CPB radioassay after solvent extraction. Normal ranges were found for plasma and urinary cortisol. The samples obtained in the morning (8:00 am) established a normal plasma cortisol range of 9.0-21.6 mug% with a mean of 15.3. range for urinary unconjugated cortisol was 12.0-41.5 mug/day (mean 26.9). Dexamethasone suppression and adrenocorticotrophic hormone stimulation of plasma and urinary cortisol were tested with individuals having normal and abnormal adrenal cortical function. RESULTS INDICATED A GOOD CLINICOPATHOLOGICAL CORRELATION. It was concluded that plasma and urinary unconjugated cortisol are reliable laboratory tests for adrenocortical function and would be the methods of choice rather than urinary 17-ketogenic steroids."} {"id": "PMID:176292", "title": "The effects of chemotherapy on the Wistar-Furth Wilms' Tumor.", "content": "An evaluation of single versus multiple therapy utilizing actinomycin D and vincristine to establish optimum therapeutic value on Wilms' tumor was completed in the present study. A Wistar/Furth Wilms' tumor model was treated with four dosage levels of actinomycin D and vincristine in single and multiple courses of treatment immediately after tumor injection. The results observed and analyzed indicated an optimum dose level for each drug and its most effective therapy course. Actinomycin D (at 300 mg/kg) in single or multiple dose was most effective, to an equal degree, in prolonging survival, decreasing the number of metastases, and the weight of the renal primary as well. Vincristine chemotherapy on a low-dose basis was associated chiefly with increased survival only.", "contents": "The effects of chemotherapy on the Wistar-Furth Wilms' Tumor. An evaluation of single versus multiple therapy utilizing actinomycin D and vincristine to establish optimum therapeutic value on Wilms' tumor was completed in the present study. A Wistar/Furth Wilms' tumor model was treated with four dosage levels of actinomycin D and vincristine in single and multiple courses of treatment immediately after tumor injection. The results observed and analyzed indicated an optimum dose level for each drug and its most effective therapy course. Actinomycin D (at 300 mg/kg) in single or multiple dose was most effective, to an equal degree, in prolonging survival, decreasing the number of metastases, and the weight of the renal primary as well. Vincristine chemotherapy on a low-dose basis was associated chiefly with increased survival only."} {"id": "PMID:176293", "title": "Application of an in-vitro perifusion technique to studies of luteinizing hormone release by rat anterior hemi-pituitaries: Self-potentiation by luteinizing hormone releasing hormone.", "content": "A technique is described for the continuous perifusion of rat adenophypophyses. Exposure of the perifused glands to repeated equal 5 min stimuli with hypothalamic extract resulted in a series of equal peaks of corticotrophin secretion, the response was proportional to log dose over the range 0 - 25-2 - 0 rat hypothalamic equivalents/ml. Repeated equal stimuli with hypothalamic extract, or with luteinizing hormone releasing hormone (LH-RH) at concentrations of 2 or 10 ng/ml, resulted in a progressively increasing series of peaks of LH secretion, i.e. a self-potentiating or priming effect. The effect took between 30 min and 1 h to develop. A delayed increase in the responsiveness of the glands was also seen with continuous incubation of anterior pituitaries with LH-RH. The relevance of these observations to the physiological control of LH secretion is discussed.", "contents": "Application of an in-vitro perifusion technique to studies of luteinizing hormone release by rat anterior hemi-pituitaries: Self-potentiation by luteinizing hormone releasing hormone. A technique is described for the continuous perifusion of rat adenophypophyses. Exposure of the perifused glands to repeated equal 5 min stimuli with hypothalamic extract resulted in a series of equal peaks of corticotrophin secretion, the response was proportional to log dose over the range 0 - 25-2 - 0 rat hypothalamic equivalents/ml. Repeated equal stimuli with hypothalamic extract, or with luteinizing hormone releasing hormone (LH-RH) at concentrations of 2 or 10 ng/ml, resulted in a progressively increasing series of peaks of LH secretion, i.e. a self-potentiating or priming effect. The effect took between 30 min and 1 h to develop. A delayed increase in the responsiveness of the glands was also seen with continuous incubation of anterior pituitaries with LH-RH. The relevance of these observations to the physiological control of LH secretion is discussed."} {"id": "PMID:176294", "title": "Ability of various factors to oppose the stimulatory effect of dibutyrylcyclic AMP on the release of melanocyte-stimulating hormone by the rat pituitary in vitro.", "content": "Various agents were tested for their ability to oppose the stimulatory effect of dibutyryl cyclic AMP on the release of the melanocyte-stimulating hormone from the rat neuro intermediate lobe in vitro. Only dopamine exhibited an inhibitory effect; serotonin, gamma-amino-butyric acid, tocinoic acid, tocinamide, the tripeptide Pro-Leu-Gly-NH2 and dibutyryl cyclic GMP were all ineffective.", "contents": "Ability of various factors to oppose the stimulatory effect of dibutyrylcyclic AMP on the release of melanocyte-stimulating hormone by the rat pituitary in vitro. Various agents were tested for their ability to oppose the stimulatory effect of dibutyryl cyclic AMP on the release of the melanocyte-stimulating hormone from the rat neuro intermediate lobe in vitro. Only dopamine exhibited an inhibitory effect; serotonin, gamma-amino-butyric acid, tocinoic acid, tocinamide, the tripeptide Pro-Leu-Gly-NH2 and dibutyryl cyclic GMP were all ineffective."} {"id": "PMID:176295", "title": "Tamoxifen as an anti-tumour agent: effect on oestrogen binding.", "content": "Tamoxifen (ICI 46,474) has been shown to possess anti-tumour properties in the dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model. During tamoxifen therapy the binding of [3H]oestradiol in vivo to uterine (P less than 0-001), vaginal (P less than 0 X 01) and tumour (P less than 0-001) tissues was significantly reduced. Tamoxifen therapy was without effect on the binding of [3H]oestradiol in heart tissue. The determination of specific oestrogen-binding components in vitro was significantly reduced (P less than 0-01) in tumours from tamoxifen-treated rats and tamoxifen inhibited the binding of [3H]oestradiol to 8S oestrogen-binding components, derived from rat uteri and DMBA-induced tumours, in vitro.", "contents": "Tamoxifen as an anti-tumour agent: effect on oestrogen binding. Tamoxifen (ICI 46,474) has been shown to possess anti-tumour properties in the dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model. During tamoxifen therapy the binding of [3H]oestradiol in vivo to uterine (P less than 0-001), vaginal (P less than 0 X 01) and tumour (P less than 0-001) tissues was significantly reduced. Tamoxifen therapy was without effect on the binding of [3H]oestradiol in heart tissue. The determination of specific oestrogen-binding components in vitro was significantly reduced (P less than 0-01) in tumours from tamoxifen-treated rats and tamoxifen inhibited the binding of [3H]oestradiol to 8S oestrogen-binding components, derived from rat uteri and DMBA-induced tumours, in vitro."} {"id": "PMID:176296", "title": "Control of oestrogen production in human pregnancy: effect of trophic hormones on steroid biosynthesis by the foetal adrenal gland in vitro.", "content": "[14C]Acetate was incorporated into dehydroepiandrosterone, pregnenolone and their sulphates and into cholesterol during incubations of adrenal tissue from three human foetuses of 10-18 weeks of gestation. No incorporation of [14C]acetate into cortisol or other 4-en-3-oxo steroids could be demonstrated. Porcine ACTH stimulated the incorporation of [14C]acetate into both dehydroepiandrosterone sulphate and cholesterol when added to incubations of adrenal tissue from foetuses of 18 weeks gestation. Such an effect was not observed with tissue from a 10-week-old foetus. Stimulation of steroid biosynthesis from [14C]acetate was also achieved by addition of human growth hormone chorionic somato-mammotrophin. These trophic hormones may therefore play some part in regulating the provision of precursors for oestrogen biosynthesis in pregnancy.", "contents": "Control of oestrogen production in human pregnancy: effect of trophic hormones on steroid biosynthesis by the foetal adrenal gland in vitro. [14C]Acetate was incorporated into dehydroepiandrosterone, pregnenolone and their sulphates and into cholesterol during incubations of adrenal tissue from three human foetuses of 10-18 weeks of gestation. No incorporation of [14C]acetate into cortisol or other 4-en-3-oxo steroids could be demonstrated. Porcine ACTH stimulated the incorporation of [14C]acetate into both dehydroepiandrosterone sulphate and cholesterol when added to incubations of adrenal tissue from foetuses of 18 weeks gestation. Such an effect was not observed with tissue from a 10-week-old foetus. Stimulation of steroid biosynthesis from [14C]acetate was also achieved by addition of human growth hormone chorionic somato-mammotrophin. These trophic hormones may therefore play some part in regulating the provision of precursors for oestrogen biosynthesis in pregnancy."} {"id": "PMID:176307", "title": "Alpha-adrenergic receptor activity, cyclic AMP and lipolysis in adipose tissue of hypothyroid man and rat.", "content": "Lipolysis and intracellular levels of cyclic AMP of adipose tissue from man and rat in both hypothyroid and euthyroid states were studied in response to stimulation by catecholamines in vitro. Hypothyroid patients were studied before and after treatment, and were also compared with euthyroid obese controls. The experimental group of rats was rendered hypothyroid by the addition of 2.9 mM-propylthiouracil to their drinking water, and their status confirmed by plasma thyroid function tests. Evidence for alpha-adrenergic receptor activity was found in rat adipose tissue, but was less marked than the pronounced alpha-adrenergic activity in human adipose tissue. Glycerol release from adipose tissue in response to noradrenaline stimulation was less marked in hypothyroidism in both species, and was related to an increased alpha-adrenergic activity. No evidence was found for increased alpha-adrenergic effects on cyclic AMP level in hypothyroid subjects, and little evidence was found in adipose tissue from hypothyroid rats. This discrepancy may be due to the presence of the phosphodiesterase inhibitor, theophylline, in the incubation system. The possible modulatory role of thyroid hormones on receptor and phosphodiesterase activity, and on lipolysis, is discussed.", "contents": "Alpha-adrenergic receptor activity, cyclic AMP and lipolysis in adipose tissue of hypothyroid man and rat. Lipolysis and intracellular levels of cyclic AMP of adipose tissue from man and rat in both hypothyroid and euthyroid states were studied in response to stimulation by catecholamines in vitro. Hypothyroid patients were studied before and after treatment, and were also compared with euthyroid obese controls. The experimental group of rats was rendered hypothyroid by the addition of 2.9 mM-propylthiouracil to their drinking water, and their status confirmed by plasma thyroid function tests. Evidence for alpha-adrenergic receptor activity was found in rat adipose tissue, but was less marked than the pronounced alpha-adrenergic activity in human adipose tissue. Glycerol release from adipose tissue in response to noradrenaline stimulation was less marked in hypothyroidism in both species, and was related to an increased alpha-adrenergic activity. No evidence was found for increased alpha-adrenergic effects on cyclic AMP level in hypothyroid subjects, and little evidence was found in adipose tissue from hypothyroid rats. This discrepancy may be due to the presence of the phosphodiesterase inhibitor, theophylline, in the incubation system. The possible modulatory role of thyroid hormones on receptor and phosphodiesterase activity, and on lipolysis, is discussed."} {"id": "PMID:176309", "title": "Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells.", "content": "Friend leukemia virus suppresses the proliferative responses of normal thymus-dependent (T) and bursa equivalent-dependent (B) lymphocytes from spleen, thymus, lymph node, and bone marrow to mitogens. The suppressive effect of Friend virus complex (FV) requires fully infectious virions. Friend erythroleukemic cells, washed to removed extracellular virus, fail to suppress concanavalin A (Con-A)-induced mitogenesis of normal spleen cells. This indicates that FV does not mediate its immunosuppressive effect via transformed erythropoietic cells. The in vitro suppressive effect of FV on lymphocyte mitogenesis is under host genetic control. Spleen, bone marrow, and thymus cells from strains of mice susceptible to FV-induced leukemogenesis in vivo were quite susceptible to the suppressive effects of FV in vitro. On the other hand, similar cells from strains of mice such as C57BL/6 resistant to Friend erythroleukemia, were quite resistant to in virto immunosuppression by FV. Mitogenesis of splenic T cells from resistant B6 mice, previously treated with 89Sr, became susceptible to suppression by FV. This indicated that the in vitro resistance of lymphocytes to FV-induced suppression is not an intrinsic property of T cells, but is controlled by marrow-dependent (M) cells which are selectively eliminated by treatment with 89Sr. M-cell function does not develop in mice less than 3-wk old. The Con A response by thymus cells from 2-wk-old B6 mice was susceptible to suppression by FV, further supporting the concept that M cells may regulate the genetic resistance to FV.", "contents": "Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells. Friend leukemia virus suppresses the proliferative responses of normal thymus-dependent (T) and bursa equivalent-dependent (B) lymphocytes from spleen, thymus, lymph node, and bone marrow to mitogens. The suppressive effect of Friend virus complex (FV) requires fully infectious virions. Friend erythroleukemic cells, washed to removed extracellular virus, fail to suppress concanavalin A (Con-A)-induced mitogenesis of normal spleen cells. This indicates that FV does not mediate its immunosuppressive effect via transformed erythropoietic cells. The in vitro suppressive effect of FV on lymphocyte mitogenesis is under host genetic control. Spleen, bone marrow, and thymus cells from strains of mice susceptible to FV-induced leukemogenesis in vivo were quite susceptible to the suppressive effects of FV in vitro. On the other hand, similar cells from strains of mice such as C57BL/6 resistant to Friend erythroleukemia, were quite resistant to in virto immunosuppression by FV. Mitogenesis of splenic T cells from resistant B6 mice, previously treated with 89Sr, became susceptible to suppression by FV. This indicated that the in vitro resistance of lymphocytes to FV-induced suppression is not an intrinsic property of T cells, but is controlled by marrow-dependent (M) cells which are selectively eliminated by treatment with 89Sr. M-cell function does not develop in mice less than 3-wk old. The Con A response by thymus cells from 2-wk-old B6 mice was susceptible to suppression by FV, further supporting the concept that M cells may regulate the genetic resistance to FV."} {"id": "PMID:176310", "title": "The role of glucose limitation in the regulation of the transport of glucose, gluconate and 2-oxogluconate, and of glucose metabolism in Pseudomonas aeruginosa.", "content": "The pathway of glucose metabolism in Pseudomonas aeruginosa was regulated by the availability of glucose and related compounds. On changing from an ammonium limitation to a glucose limitation, the organism responded by adjusting its metabolism substantially from the extracellular direct oxidative pathway to the intracellular phosphorylative route. This change was achieved by repression of the transport systems for gluconate and 2-oxogluconate and of the associated enzymes for 2-oxogluconate metabolism and gluconate kinase, while increasing the levels of glucose transport, hexokinase and glucose 6-phosphate dehydrogenase. The role of gluconate, produced by the action of glucose dehydrogenase, as a major inhibitory factor for glucose transport, and the possible significance of these regulatory mechanisms to the organism in its natural environment, are discussed.", "contents": "The role of glucose limitation in the regulation of the transport of glucose, gluconate and 2-oxogluconate, and of glucose metabolism in Pseudomonas aeruginosa. The pathway of glucose metabolism in Pseudomonas aeruginosa was regulated by the availability of glucose and related compounds. On changing from an ammonium limitation to a glucose limitation, the organism responded by adjusting its metabolism substantially from the extracellular direct oxidative pathway to the intracellular phosphorylative route. This change was achieved by repression of the transport systems for gluconate and 2-oxogluconate and of the associated enzymes for 2-oxogluconate metabolism and gluconate kinase, while increasing the levels of glucose transport, hexokinase and glucose 6-phosphate dehydrogenase. The role of gluconate, produced by the action of glucose dehydrogenase, as a major inhibitory factor for glucose transport, and the possible significance of these regulatory mechanisms to the organism in its natural environment, are discussed."} {"id": "PMID:176311", "title": "Extracellular cyclic AMP-phosphodiesterase accelerates differentiation in Dictyostelium discoideum.", "content": "Extracellular cyclic AMP-phosphodiesterase accelerates the development of aggregation competence in Dictyostelium discoideum when present during the preaggregation stage. The effect on development appears to depend only on hydrolysis of extracellular cyclic AMP and not on other properties of the phosphodiesterase molecule. Extracellular cyclic AMP-phosphodiesterase, as a promoter of differentiation, acts mainly throughout the first half of interphase. Our evidence supports the proposal that cyclic AMP oscillations control the rate and possibly the initiation of development. Since extracellular cyclic AMP-phosphodiesterase acts from the beginning of interphase cyclic AMP oscillations may also occur from early interphase, at least in the presence of this enzyme. This would imply that the cyclic AMP oscillator is a determinant, but not a product, of the developmental programme.", "contents": "Extracellular cyclic AMP-phosphodiesterase accelerates differentiation in Dictyostelium discoideum. Extracellular cyclic AMP-phosphodiesterase accelerates the development of aggregation competence in Dictyostelium discoideum when present during the preaggregation stage. The effect on development appears to depend only on hydrolysis of extracellular cyclic AMP and not on other properties of the phosphodiesterase molecule. Extracellular cyclic AMP-phosphodiesterase, as a promoter of differentiation, acts mainly throughout the first half of interphase. Our evidence supports the proposal that cyclic AMP oscillations control the rate and possibly the initiation of development. Since extracellular cyclic AMP-phosphodiesterase acts from the beginning of interphase cyclic AMP oscillations may also occur from early interphase, at least in the presence of this enzyme. This would imply that the cyclic AMP oscillator is a determinant, but not a product, of the developmental programme."} {"id": "PMID:176312", "title": "Regulation of arginine and pyrimidine biosynthesis in Pseudomonas putida.", "content": "Repression of biosynthetic enzyme synthesis in Pseudomonas putida is incomplete even when the bacteria are growing in a nutritionally complex environment. The synthesis of four of the enzymes of the arginine biosynthetic pathway (N-acetyl-alpha-glutamokinase/N-acetylglutamate-gamma-semialdehyde dehydrogenase, ornithine carbamoyltransferase and acetylornithine-delta-transaminase) could be repressed and derepressed, but the maximum difference observed between repressed and derepressed levels for any enzyme of the pathway was only 5-fold (for ornithine carbamoyltransferase). No repression of five enzymes of the pyrimidine biosynthetic pathway (aspartate carbamoyltransferase, dihydro-orotase, dihydro-orotate dehydrogenase, orotidine-5'-phosphate pyrophosphorylase and orotidine-5'-phosphate decarboxylase) could be detected on addition of pyrimidines to minimal asparagine cultures of P. putida A90, but a 1-5- to 2-fold degree of derepression was found following pyrimidine starvation of pyrimidine auxotrophic mutants of P. putida A90. Aspartate carbamoyltransferase in crude extracts of P. putida A90 was inhibited in vitro by (in order of efficiency) pyrophosphate, CTP, UTP and ATP, at limiting but not at saturating concentrations of carbamoyl phosphate.", "contents": "Regulation of arginine and pyrimidine biosynthesis in Pseudomonas putida. Repression of biosynthetic enzyme synthesis in Pseudomonas putida is incomplete even when the bacteria are growing in a nutritionally complex environment. The synthesis of four of the enzymes of the arginine biosynthetic pathway (N-acetyl-alpha-glutamokinase/N-acetylglutamate-gamma-semialdehyde dehydrogenase, ornithine carbamoyltransferase and acetylornithine-delta-transaminase) could be repressed and derepressed, but the maximum difference observed between repressed and derepressed levels for any enzyme of the pathway was only 5-fold (for ornithine carbamoyltransferase). No repression of five enzymes of the pyrimidine biosynthetic pathway (aspartate carbamoyltransferase, dihydro-orotase, dihydro-orotate dehydrogenase, orotidine-5'-phosphate pyrophosphorylase and orotidine-5'-phosphate decarboxylase) could be detected on addition of pyrimidines to minimal asparagine cultures of P. putida A90, but a 1-5- to 2-fold degree of derepression was found following pyrimidine starvation of pyrimidine auxotrophic mutants of P. putida A90. Aspartate carbamoyltransferase in crude extracts of P. putida A90 was inhibited in vitro by (in order of efficiency) pyrophosphate, CTP, UTP and ATP, at limiting but not at saturating concentrations of carbamoyl phosphate."} {"id": "PMID:176313", "title": "Morphogenesis of picornaviruses: characterization and assembly of bovine enterovirus subviral particles.", "content": "Bovine enterovirus-I (BEV-I) infection results in the production of a low amount of infective virus. A large number of non-infectious virus particles can be detected in BEV-I lysates by haemagglutination. Attempts to isolate DI particles that might be responsible for this effect failed. However, infected cells were shown to contain large amounts of 80S particles as well as lesser amounts of 160S, 130S, 45S, 14S and 5S particles. The proportion of these subviral particles detectable by density gradient sedimentation depended on the ionic strength of the gradient buffer. At high ionic strength 130S particles were transformed into 160S particles, and 45S into 80S particles. The polypeptide composition of each virus particle was examined. Pulse-chase experiments confirmed that 80S particles were the predominant virus particles accumulating. No precursor-product relationship could be established for the 80S particle, although 5S and 14S particles were shown to be precursors of mature virus particles.", "contents": "Morphogenesis of picornaviruses: characterization and assembly of bovine enterovirus subviral particles. Bovine enterovirus-I (BEV-I) infection results in the production of a low amount of infective virus. A large number of non-infectious virus particles can be detected in BEV-I lysates by haemagglutination. Attempts to isolate DI particles that might be responsible for this effect failed. However, infected cells were shown to contain large amounts of 80S particles as well as lesser amounts of 160S, 130S, 45S, 14S and 5S particles. The proportion of these subviral particles detectable by density gradient sedimentation depended on the ionic strength of the gradient buffer. At high ionic strength 130S particles were transformed into 160S particles, and 45S into 80S particles. The polypeptide composition of each virus particle was examined. Pulse-chase experiments confirmed that 80S particles were the predominant virus particles accumulating. No precursor-product relationship could be established for the 80S particle, although 5S and 14S particles were shown to be precursors of mature virus particles."} {"id": "PMID:176314", "title": "Characterization of an enterovirus associated with acute infectious lymphocytosis.", "content": "An enterovirus (EVU-16) previously isolated from children with acute infectious lymphocytosis has been further characterized. The EVU-16 virus sediments as a 135S particle in sucrose gradients, has a density of 1-335 g/ml in CsCl, contains 4 polypeptides and has a single stranded RNA genome sedimenting at 35S. These structural features as well as the presence of a virus-related particle, the procapsid, are similar to those of other enteroviruses. However, the largest polypeptide of EVU-16 is 49000 daltons, which is considerably larger than the corresponding polypeptide from poliovirus; the sizes of the other three viral polypeptides were similar in both viruses. Attempts to induce lymphocytosis by the inoculation of EVU-16 into various animals, including immunologically aberrant 'nude' mice, were unsuccessful.", "contents": "Characterization of an enterovirus associated with acute infectious lymphocytosis. An enterovirus (EVU-16) previously isolated from children with acute infectious lymphocytosis has been further characterized. The EVU-16 virus sediments as a 135S particle in sucrose gradients, has a density of 1-335 g/ml in CsCl, contains 4 polypeptides and has a single stranded RNA genome sedimenting at 35S. These structural features as well as the presence of a virus-related particle, the procapsid, are similar to those of other enteroviruses. However, the largest polypeptide of EVU-16 is 49000 daltons, which is considerably larger than the corresponding polypeptide from poliovirus; the sizes of the other three viral polypeptides were similar in both viruses. Attempts to induce lymphocytosis by the inoculation of EVU-16 into various animals, including immunologically aberrant 'nude' mice, were unsuccessful."} {"id": "PMID:176315", "title": "Infectivity, oncogenicity and transforming ability of BK virus and BK virus DNA.", "content": "The human papovavirus, BK, appeared weakly oncogenic in newborn hamsters and was able to induce in vitro transformation of rat kidney cells. The infectivity of BK virus DNA was determined by employing the DEAE-dextran method. In human embryonic cells the infectivity was approx. 10(5) p.f.u./mug of DNA. The transforming ability of BK virus in primary rat kidney cells was measured by employing the calcium method and appeared to vary from 1 to 10 foci per mug of DNA.", "contents": "Infectivity, oncogenicity and transforming ability of BK virus and BK virus DNA. The human papovavirus, BK, appeared weakly oncogenic in newborn hamsters and was able to induce in vitro transformation of rat kidney cells. The infectivity of BK virus DNA was determined by employing the DEAE-dextran method. In human embryonic cells the infectivity was approx. 10(5) p.f.u./mug of DNA. The transforming ability of BK virus in primary rat kidney cells was measured by employing the calcium method and appeared to vary from 1 to 10 foci per mug of DNA."} {"id": "PMID:176325", "title": "Electrophysiological changes during episodes of the Kleine-Levin syndrome.", "content": "Diurnal EEGs of a 17 year old male with the Kleine-Levin syndrome revealed moderate diffuse abnormalities and stage REM at sleep onset during attacks. Overnight, stages 3, 4, and REM of sleep were decreased, but sleep onset REM stage was not seen. These records returned to normal between attacks.", "contents": "Electrophysiological changes during episodes of the Kleine-Levin syndrome. Diurnal EEGs of a 17 year old male with the Kleine-Levin syndrome revealed moderate diffuse abnormalities and stage REM at sleep onset during attacks. Overnight, stages 3, 4, and REM of sleep were decreased, but sleep onset REM stage was not seen. These records returned to normal between attacks."} {"id": "PMID:176326", "title": "Motor nerve conduction study in patients on diphenylhydantoin therapy.", "content": "Mean motor conduction velocity of posterior tibial nerves was significantly reduced in epileptic patients treated with diphenylhydantoin formore than 10 years or in patients with serum diphenylhydantoin level above 20 mug/ml. Subnormal serum folate was not responsible for this reduction and clinical peripheral neuropathy was infrequent.", "contents": "Motor nerve conduction study in patients on diphenylhydantoin therapy. Mean motor conduction velocity of posterior tibial nerves was significantly reduced in epileptic patients treated with diphenylhydantoin formore than 10 years or in patients with serum diphenylhydantoin level above 20 mug/ml. Subnormal serum folate was not responsible for this reduction and clinical peripheral neuropathy was infrequent."} {"id": "PMID:176327", "title": "Pure motor hemiplegia secondary to brain-stem tumour.", "content": "'Pure motor hemiplegia' is a common stroke syndrome defined by Fisher as paralysis of face, arm, and leg on one side, unaccompanied by sensory signs, visual field defect, aphasia, or apractognosia. It occurs almost exclusively in hypertensive patients and carried a good prognosis. We report a case of a normotensive patient in whom pure motor hemiplegia was the presenting feature, not of a cerebrovascular syndrome, but of a pontine glioblastoma. We note that brain-stem tumours may masquerade as brain-stem strokes.", "contents": "Pure motor hemiplegia secondary to brain-stem tumour. 'Pure motor hemiplegia' is a common stroke syndrome defined by Fisher as paralysis of face, arm, and leg on one side, unaccompanied by sensory signs, visual field defect, aphasia, or apractognosia. It occurs almost exclusively in hypertensive patients and carried a good prognosis. We report a case of a normotensive patient in whom pure motor hemiplegia was the presenting feature, not of a cerebrovascular syndrome, but of a pontine glioblastoma. We note that brain-stem tumours may masquerade as brain-stem strokes."} {"id": "PMID:176328", "title": "Adenyl cyclase system and cerebral energy state.", "content": "The energy charge potential of the cerebral adenylate system, the cerebral lactate: pyruvate system, and the cerebral glycogen level were used to characterize the cerebral energy state of the brain. Cerebral adenyl cyclase activity and cyclic AMP concentrations were investigated to evaluate their possible influence on the regulatory processes in brain metabolism. These biochemical parameters were evaluated on the cortical motor area of the brain of the beagle dog in hypovolaemic hypotension during acute hypoxia (obtained by altering the composition of the inhalation mixture) and during the post-hypoxic recovery (three minutes after the restoration of normal ventilation). This experimental model of acute hypoxia was also used for investigating the action of some substances acting at beta-adrenergic receptor level or at vascular level. The substances were perfused into the carotid artery at the rate of 0.5 ml/min for three to six minutes. During the first stage of hypoxia, the adenyl cyclase system is probably an important biochemical regulatory factor. This system becomes less important when a critical threshold is crossed (oxygen arterial partial pressure less than 25-20 mmHg) below which other factors become rate-limiting. A beta-receptor stimulating agent enhanced the mechanisms of physiological post-hypoxic recovery; inhibition of this action was obtained with a beta-receptor blocking agent. Under these experimental conditions, no correlation existed between the vascular effects of the agents and brain metabolism.", "contents": "Adenyl cyclase system and cerebral energy state. The energy charge potential of the cerebral adenylate system, the cerebral lactate: pyruvate system, and the cerebral glycogen level were used to characterize the cerebral energy state of the brain. Cerebral adenyl cyclase activity and cyclic AMP concentrations were investigated to evaluate their possible influence on the regulatory processes in brain metabolism. These biochemical parameters were evaluated on the cortical motor area of the brain of the beagle dog in hypovolaemic hypotension during acute hypoxia (obtained by altering the composition of the inhalation mixture) and during the post-hypoxic recovery (three minutes after the restoration of normal ventilation). This experimental model of acute hypoxia was also used for investigating the action of some substances acting at beta-adrenergic receptor level or at vascular level. The substances were perfused into the carotid artery at the rate of 0.5 ml/min for three to six minutes. During the first stage of hypoxia, the adenyl cyclase system is probably an important biochemical regulatory factor. This system becomes less important when a critical threshold is crossed (oxygen arterial partial pressure less than 25-20 mmHg) below which other factors become rate-limiting. A beta-receptor stimulating agent enhanced the mechanisms of physiological post-hypoxic recovery; inhibition of this action was obtained with a beta-receptor blocking agent. Under these experimental conditions, no correlation existed between the vascular effects of the agents and brain metabolism."} {"id": "PMID:176329", "title": "Morphology and enzyme histochemistry of dorsal muscles of the cat neck.", "content": "An examination has been made of the five dorsal muscles of the cat neck which insert into the lamboidal crest. The three larger muscles, splenius, biventer cervicis, and complexus, are characterized by the presence of tendinous inscriptions which serve as the insertion points of shorter muscle fibers which do not run the length of the muscle. Longer fibers are bound by the inscriptions and, thus can transmit tension developed by shorter fibers. These three muscles are multiply innervater by nerves emerging from upper cervical spinal roots. Multiple innervation is not associated with multiple end plates but with arrangement so that lower roots innervate a high proportion of short fibers and higher roots, a high proportion of long fibers. Occipitoscapularis and rectus capitis major are, by comparison, simple muscles, each with a single motor nerve. Of the muscles examined, occipitoscapularis alone does not have its origin on the vertebral column but on the scapula, and is unlikely to have any major function in head movement.", "contents": "Morphology and enzyme histochemistry of dorsal muscles of the cat neck. An examination has been made of the five dorsal muscles of the cat neck which insert into the lamboidal crest. The three larger muscles, splenius, biventer cervicis, and complexus, are characterized by the presence of tendinous inscriptions which serve as the insertion points of shorter muscle fibers which do not run the length of the muscle. Longer fibers are bound by the inscriptions and, thus can transmit tension developed by shorter fibers. These three muscles are multiply innervater by nerves emerging from upper cervical spinal roots. Multiple innervation is not associated with multiple end plates but with arrangement so that lower roots innervate a high proportion of short fibers and higher roots, a high proportion of long fibers. Occipitoscapularis and rectus capitis major are, by comparison, simple muscles, each with a single motor nerve. Of the muscles examined, occipitoscapularis alone does not have its origin on the vertebral column but on the scapula, and is unlikely to have any major function in head movement."} {"id": "PMID:176330", "title": "Morphological correlates of synaptic transmission in lamprey spinal cord.", "content": "The dye Procion brown was used to identify in the light and electron microscope, synaptic contacts made between monosynaptically coupled neurons in the lamprey spinal cord whose synaptic interaction had been recorded. Synaptic contacts were made on different dendrites of the postsynaptic cell at different distances from the soma. Some of the contacts were made on dentritic spines and some on the smooth shaft of the dentrites. Serial sections through synaptic contacts made on dendritic processess of the postsynaptic cells were used for three-dimensional reconstruction of the synapses using computer graphics techniques. The computer reconstructions and detailed examination of the serial EM micrographs revealed the large proliferation of membrane involved in making these en passant synapses as well as the morphological changes due to stimulation of the presynaptic axon. These changes include depletion of synaptic vesicles and formation of complex vesicles and synaptic cisternae. Besides chemical synaptic contacts, four electrotonic contacts were located, confirming the mixed electrochemical synaptic response recorded from the postsynaptic cell. The mean quantum content was estimated and compared with the estimate of the available transmitter pool, assuming the quantal release hypothesis applies at these synapses. The total transmitter pool was estimated by counting all synaptic vesicles in all synaptic contacts. It was estimated that about 6% of the total transmitter pool is available for release at these synapses. This compares with less than 1% at the neuromuscular junction and about 20% at sympathetic synapses. These results support the hypothesis that synaptic vesicles may be recycled as described by Heuser and Reese (22) at the neuromuscular junction. Ongoing studies are investigating the effect on a variety of synaptic junctions to stimulation for different periods of time of presynaptic axons. The methods described in this study can also be used to test the models of synaptic interaction on dendritic trees described by Rall (39) and Jack and Redman (24).", "contents": "Morphological correlates of synaptic transmission in lamprey spinal cord. The dye Procion brown was used to identify in the light and electron microscope, synaptic contacts made between monosynaptically coupled neurons in the lamprey spinal cord whose synaptic interaction had been recorded. Synaptic contacts were made on different dendrites of the postsynaptic cell at different distances from the soma. Some of the contacts were made on dentritic spines and some on the smooth shaft of the dentrites. Serial sections through synaptic contacts made on dendritic processess of the postsynaptic cells were used for three-dimensional reconstruction of the synapses using computer graphics techniques. The computer reconstructions and detailed examination of the serial EM micrographs revealed the large proliferation of membrane involved in making these en passant synapses as well as the morphological changes due to stimulation of the presynaptic axon. These changes include depletion of synaptic vesicles and formation of complex vesicles and synaptic cisternae. Besides chemical synaptic contacts, four electrotonic contacts were located, confirming the mixed electrochemical synaptic response recorded from the postsynaptic cell. The mean quantum content was estimated and compared with the estimate of the available transmitter pool, assuming the quantal release hypothesis applies at these synapses. The total transmitter pool was estimated by counting all synaptic vesicles in all synaptic contacts. It was estimated that about 6% of the total transmitter pool is available for release at these synapses. This compares with less than 1% at the neuromuscular junction and about 20% at sympathetic synapses. These results support the hypothesis that synaptic vesicles may be recycled as described by Heuser and Reese (22) at the neuromuscular junction. Ongoing studies are investigating the effect on a variety of synaptic junctions to stimulation for different periods of time of presynaptic axons. The methods described in this study can also be used to test the models of synaptic interaction on dendritic trees described by Rall (39) and Jack and Redman (24)."} {"id": "PMID:176331", "title": "Glioblastoma multiforme in children.", "content": "Of 488 children with central nervous system neoplasms, 43 (8.8%) had glioblastomas, 22 of which were in the cerebral hemispheres, 16 in the brain stem, two in the cerebellum, and three in the spinal cord. The male to female ratio was 3:2. Glioblastoma multiforme of the cerebral hemispheres occurred at a mean age of 12.7 years, and the frontal lobe was the most commonly involved. Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months). Brain stem glioblastomas occurred at a mean age of 6.7 years, with the pons as the most frequent site. Nausea or vomiting (50%) and headache (36%) were the main presenting symptoms; the major physical findings were ataxia (43%), cranial nerve palsies (28%), and paresis (28%). The length of survival was greatest with radiation alone (10.5 months). The period of survival of children with glioblastoma multiforme was significantly increased with steroid therapy. Glioblastoma multiforme behaves similarly in children and adults. Intracranial glioblastomas have a more rapidly fatal course than that of other similarly situated gliomas in childhood.", "contents": "Glioblastoma multiforme in children. Of 488 children with central nervous system neoplasms, 43 (8.8%) had glioblastomas, 22 of which were in the cerebral hemispheres, 16 in the brain stem, two in the cerebellum, and three in the spinal cord. The male to female ratio was 3:2. Glioblastoma multiforme of the cerebral hemispheres occurred at a mean age of 12.7 years, and the frontal lobe was the most commonly involved. Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months). Brain stem glioblastomas occurred at a mean age of 6.7 years, with the pons as the most frequent site. Nausea or vomiting (50%) and headache (36%) were the main presenting symptoms; the major physical findings were ataxia (43%), cranial nerve palsies (28%), and paresis (28%). The length of survival was greatest with radiation alone (10.5 months). The period of survival of children with glioblastoma multiforme was significantly increased with steroid therapy. Glioblastoma multiforme behaves similarly in children and adults. Intracranial glioblastomas have a more rapidly fatal course than that of other similarly situated gliomas in childhood."} {"id": "PMID:176332", "title": "Localization of myocardial disorders other than infarction with 99mTc-labeled phosphate agents.", "content": "Myocardial studies with 99mTc-labeled phosphate agents were obtained in 20 patients without demonstrable cardiovascular disease, 24 patients with unstable arteriosclerotic heart disease (ASHD) without acute infarction, and six patients with myocardiopathy. The patients without cardiovascular disease showed no localization or tracer; the patients with unstable ASHD and without acute infarction showed nonfocal ill-defined accumulation of tracer; and the patients with myocardiopathy showed diffuse accummulation of tracer throughout the confines of an enlarged cardiac outline. Careful evaluation of both the distribution and intensity of the activity, in conjunction with the clinical picture, allows differentiation among these disease processes. Since ischemic areas around infarcted tissue may show increased activity, the value of this technique for sizing acute myocardial infarction may be limited.", "contents": "Localization of myocardial disorders other than infarction with 99mTc-labeled phosphate agents. Myocardial studies with 99mTc-labeled phosphate agents were obtained in 20 patients without demonstrable cardiovascular disease, 24 patients with unstable arteriosclerotic heart disease (ASHD) without acute infarction, and six patients with myocardiopathy. The patients without cardiovascular disease showed no localization or tracer; the patients with unstable ASHD and without acute infarction showed nonfocal ill-defined accumulation of tracer; and the patients with myocardiopathy showed diffuse accummulation of tracer throughout the confines of an enlarged cardiac outline. Careful evaluation of both the distribution and intensity of the activity, in conjunction with the clinical picture, allows differentiation among these disease processes. Since ischemic areas around infarcted tissue may show increased activity, the value of this technique for sizing acute myocardial infarction may be limited."} {"id": "PMID:176333", "title": "Bone scan patterns of patients with diffuse metastatic carcinoma of the axial skeleton.", "content": "Bone scan findings (using 99mTc-stannous pyrophosphate) in five patients with diffuse metastatic carcinoma of the axial skeleton are reviewed. Although there were few visually recognizable asymmetries of tracer localization, the diffuse involvement was diagnosed through abnormally elevated counting rates in the axial skeleton, decreased visualization of the kidneys, and faint or absent visualization of the appendicular skeleton.", "contents": "Bone scan patterns of patients with diffuse metastatic carcinoma of the axial skeleton. Bone scan findings (using 99mTc-stannous pyrophosphate) in five patients with diffuse metastatic carcinoma of the axial skeleton are reviewed. Although there were few visually recognizable asymmetries of tracer localization, the diffuse involvement was diagnosed through abnormally elevated counting rates in the axial skeleton, decreased visualization of the kidneys, and faint or absent visualization of the appendicular skeleton."} {"id": "PMID:176334", "title": "Nature of the dietary carbohydrate and metabolism of glycosaminoglycans and glycoproteins in rats.", "content": "The polysaccharide from blackgram (Phaseolus mungo) has been previously reported to cause lower cholesterol, phospholipids and triglyceride levels in rats fed either low-or high-fat diets containing cholesterol. The effect of this polysaccharide fraction as compared to that of glucose and sucrose on the metabolism of glycosaminoglycans and glycoprotein has been studied. The pattern of change in the levels of different glycosaminoglycans varied in the different tissues. Sucrose fed animals gave lower levels of sulphated glycosaminoglycans in the aorta and liver. The polysaccharide and glucose fed animals gave comparable values in the aorta except in the case of chondroitin sulfate B which was higher and heparin lower in the polysaccharide group. L-glutamine:D-fructose-6-phosphate amino transferase and UDPG dehydrogenase were lowest in the sucrose fed animals and highest in the polysacchride group with the animals in the glucose group showing intermediate values, but UDPG pyrophosphorylase, while highest in the polysaccharide group, was similar in the glucose and sucrose groups. Some of the degrading enzymes studied-beta-glucuronidase, hyaluronidase and aryl sulphatase-were highest in the sucrose group and generally lowest in the polysaccharide group. Levels of 3'-phosphoadenosine-5'-phosphosulphate, the biological sulphating agent, the sulphate activating system which includes ATP sulphurylase and APS kinase and sulphotransferase activity were also lowest in the sucrose fed group and highest in the polysaccharide group. The glycoprotein concentration was highest in the liver and lowest in the kidney in the sucrose group.", "contents": "Nature of the dietary carbohydrate and metabolism of glycosaminoglycans and glycoproteins in rats. The polysaccharide from blackgram (Phaseolus mungo) has been previously reported to cause lower cholesterol, phospholipids and triglyceride levels in rats fed either low-or high-fat diets containing cholesterol. The effect of this polysaccharide fraction as compared to that of glucose and sucrose on the metabolism of glycosaminoglycans and glycoprotein has been studied. The pattern of change in the levels of different glycosaminoglycans varied in the different tissues. Sucrose fed animals gave lower levels of sulphated glycosaminoglycans in the aorta and liver. The polysaccharide and glucose fed animals gave comparable values in the aorta except in the case of chondroitin sulfate B which was higher and heparin lower in the polysaccharide group. L-glutamine:D-fructose-6-phosphate amino transferase and UDPG dehydrogenase were lowest in the sucrose fed animals and highest in the polysacchride group with the animals in the glucose group showing intermediate values, but UDPG pyrophosphorylase, while highest in the polysaccharide group, was similar in the glucose and sucrose groups. Some of the degrading enzymes studied-beta-glucuronidase, hyaluronidase and aryl sulphatase-were highest in the sucrose group and generally lowest in the polysaccharide group. Levels of 3'-phosphoadenosine-5'-phosphosulphate, the biological sulphating agent, the sulphate activating system which includes ATP sulphurylase and APS kinase and sulphotransferase activity were also lowest in the sucrose fed group and highest in the polysaccharide group. The glycoprotein concentration was highest in the liver and lowest in the kidney in the sucrose group."} {"id": "PMID:176335", "title": "Salivary gland tumors: review of 643 cases.", "content": "643 cases of salivary gland tumors constitute two series of histological sections that were studied from hospitals and dental schools in Southeast Scotland and Southern Ontario. The Scottish series represented epithelial tumors of the parotid and intra-oral salivary glands, but the Canadian series also included tumors of the submandibular and sublingual glands. Classification was based on that recommended by the World Health Organisation (Thackray 1972). While direct statiscal comparisons between the two series are not appropriate, the differences between them suggest that malignant tumors are more common in Canada. The Scottish series contains the largest proportion of benign salivary tumors so far reported. In the Scottish series, 88.7% of parotid tumors were benign compared with 51.9% of Canadian series. In the Canadian series from the submandibular glands, 21.2% only were benign. Of the intra-oral salivary tumors, 62.2% from the Scottish series were benign compared with only 34.7% from the Canadian series.", "contents": "Salivary gland tumors: review of 643 cases. 643 cases of salivary gland tumors constitute two series of histological sections that were studied from hospitals and dental schools in Southeast Scotland and Southern Ontario. The Scottish series represented epithelial tumors of the parotid and intra-oral salivary glands, but the Canadian series also included tumors of the submandibular and sublingual glands. Classification was based on that recommended by the World Health Organisation (Thackray 1972). While direct statiscal comparisons between the two series are not appropriate, the differences between them suggest that malignant tumors are more common in Canada. The Scottish series contains the largest proportion of benign salivary tumors so far reported. In the Scottish series, 88.7% of parotid tumors were benign compared with 51.9% of Canadian series. In the Canadian series from the submandibular glands, 21.2% only were benign. Of the intra-oral salivary tumors, 62.2% from the Scottish series were benign compared with only 34.7% from the Canadian series."} {"id": "PMID:176339", "title": "Histochemical characteristics of muco-substances in three soft-tissue tumours.", "content": "The mucosubstances present in myxoid liposarcomas, malignant fibrous histiocytomas and intramuscular myxomas were investigated. The results suggest that such investigations are unlikely to provide a useful diagnostic aid in these three lesions.", "contents": "Histochemical characteristics of muco-substances in three soft-tissue tumours. The mucosubstances present in myxoid liposarcomas, malignant fibrous histiocytomas and intramuscular myxomas were investigated. The results suggest that such investigations are unlikely to provide a useful diagnostic aid in these three lesions."} {"id": "PMID:176344", "title": "Retardation of dissolution and growth of calcium oxalate monohydrate.", "content": "The kinetics of dissolution and growth of calcium oxalate monohydrate were examined in the presence of small concentrations of pyrophosphate, chlorophyll, and other agents. Data presented show that the retardation in mass transport in both processes is controlled by the nature of the additive, its concentration, and the way the additives are combined in the dissolution medium. Dissolution was studied using a particle counter method, and growth was conducted in a gel system under the slow diffusion of the reacting ions. Results obtained show that chlorophyll is more active than other inhibitors studied and suggest a higher surface adsorption intensity on the primary sources of the crystal surface.", "contents": "Retardation of dissolution and growth of calcium oxalate monohydrate. The kinetics of dissolution and growth of calcium oxalate monohydrate were examined in the presence of small concentrations of pyrophosphate, chlorophyll, and other agents. Data presented show that the retardation in mass transport in both processes is controlled by the nature of the additive, its concentration, and the way the additives are combined in the dissolution medium. Dissolution was studied using a particle counter method, and growth was conducted in a gel system under the slow diffusion of the reacting ions. Results obtained show that chlorophyll is more active than other inhibitors studied and suggest a higher surface adsorption intensity on the primary sources of the crystal surface."} {"id": "PMID:176345", "title": "Antinociceptive effects of lanthanum and cerium in nontolerant and morphine tolerant-dependent animals.", "content": "Intracerebroventricularly (i.vt.) administered lanthanum chloride was found to produce antinociceptive effects as measured by the mouse tail-flick and hot plate tests and the rat tail-flick test. These antinociceptive effects were reduced by peripheral administration of the narcotic antagonist naloxone or by i.vt. administration of calcium chloride. In addition, animals made tolerant to morphine were also tolerant to the effects of La+++. In morphine-dependent mice, the incidence of both abrupt and naloxone-precipitated withdrawal jumping was reduced by La+++ administration. In view of the known inhibitory effects of La+++ on Ca++ binding and movement, these findings suggest that alterations in Ca++ localization may be involved in the analgetic action of narcotic drugs as well as the development of narcotic tolerance and dependence.", "contents": "Antinociceptive effects of lanthanum and cerium in nontolerant and morphine tolerant-dependent animals. Intracerebroventricularly (i.vt.) administered lanthanum chloride was found to produce antinociceptive effects as measured by the mouse tail-flick and hot plate tests and the rat tail-flick test. These antinociceptive effects were reduced by peripheral administration of the narcotic antagonist naloxone or by i.vt. administration of calcium chloride. In addition, animals made tolerant to morphine were also tolerant to the effects of La+++. In morphine-dependent mice, the incidence of both abrupt and naloxone-precipitated withdrawal jumping was reduced by La+++ administration. In view of the known inhibitory effects of La+++ on Ca++ binding and movement, these findings suggest that alterations in Ca++ localization may be involved in the analgetic action of narcotic drugs as well as the development of narcotic tolerance and dependence."} {"id": "PMID:176346", "title": "Decreased vascular relaxation in hypertension.", "content": "Relaxation of spirally cut aortic strips was diminished in vessels from both spontaneously hypertensive rats and renal hypertensive rats. Aortic relaxation was decreased in response to the cyclic nucleotides and the beta adrenergic stimulant, isoproterenol, in both models, of hypertension. Defective aortic relaxation also occurred with two other vasodilators, nitroglycerin and adenosine. Further evidence for a reduced relaxant ability of blood vessels from hypertensive rats was obtained by measuring aortic relaxation after exposure and subsequent removal of vascular contractile agonists. The time for aortic preparations from spontaneously hypertensive rats to relax to base-line tension after maximum contraction with norepinephrine, serotonin and potassium chloride was significantly prolonged compared to recovery time for vessels from Kyoto Wistar normotensive rats. Treatment of the spontaneously hypertensive rat with reserpine, but not hydralazine, resulted in an improved ability of aortic preparations to relax. Based on these data, we propose that defects in vascular relaxation may contribute to hypertension and that some antihypertensive drugs may improve or facilitate vascular relaxation.", "contents": "Decreased vascular relaxation in hypertension. Relaxation of spirally cut aortic strips was diminished in vessels from both spontaneously hypertensive rats and renal hypertensive rats. Aortic relaxation was decreased in response to the cyclic nucleotides and the beta adrenergic stimulant, isoproterenol, in both models, of hypertension. Defective aortic relaxation also occurred with two other vasodilators, nitroglycerin and adenosine. Further evidence for a reduced relaxant ability of blood vessels from hypertensive rats was obtained by measuring aortic relaxation after exposure and subsequent removal of vascular contractile agonists. The time for aortic preparations from spontaneously hypertensive rats to relax to base-line tension after maximum contraction with norepinephrine, serotonin and potassium chloride was significantly prolonged compared to recovery time for vessels from Kyoto Wistar normotensive rats. Treatment of the spontaneously hypertensive rat with reserpine, but not hydralazine, resulted in an improved ability of aortic preparations to relax. Based on these data, we propose that defects in vascular relaxation may contribute to hypertension and that some antihypertensive drugs may improve or facilitate vascular relaxation."} {"id": "PMID:176347", "title": "Analysis of pairs of individual Ia-E.P.S.P.S in single motoneurones.", "content": "1. Recordings of individual e.p.s.p.s evoked by the action of single medial gastrocnemius Ia fibres have been made from medial gastrocnemius motoneurones. In many motoneurones the action of two Ia fibres has been observed and the properties of the e.p.s.p.s compared. 2. For sixty-three pairs of averaged e.p.s.p.s, each from the same motoneurone, the ratio of half-widths was plotted against the ratio of rise times. These results were compared with theoretical values derived from the Rall compartmental model. It was found that variations in synaptic current time courses and differences in the termination of localized synaptic terminals were not sufficient to account for all the data. 3. Amplitude and rise time were inversely related but the correlation coefficient was very low. For pairs of e.p.s.p.s in the same motoneurone the e.p.s.p. with the fast rise time was larger than that with the slow rise time in forty-eight of sixty-three cases. 4. In a given motoneurone individual e.p.s.p.s evoked by the action of different Ia fibres did not vary greatly in amplitude. The ratio of peak amplitudes was less than 3 for 86% of the pairs of e.p.s.p.s examined, and the maximum was 4-8. 5. Amplitude histograms were constructed for individual e.p.s.p.s at thirty-three synapses. Twenty-two of them could be shown to satisfy the Poisson law. The others satisfied the binomial law or neither. 6. Within a given motoneurone the amplitude of an e.p.s.p. is closely related to the mean number of quanta released but not to the amplitude of the unit e.p.s.p. produced by the action of a single quantum of transmitter.", "contents": "Analysis of pairs of individual Ia-E.P.S.P.S in single motoneurones. 1. Recordings of individual e.p.s.p.s evoked by the action of single medial gastrocnemius Ia fibres have been made from medial gastrocnemius motoneurones. In many motoneurones the action of two Ia fibres has been observed and the properties of the e.p.s.p.s compared. 2. For sixty-three pairs of averaged e.p.s.p.s, each from the same motoneurone, the ratio of half-widths was plotted against the ratio of rise times. These results were compared with theoretical values derived from the Rall compartmental model. It was found that variations in synaptic current time courses and differences in the termination of localized synaptic terminals were not sufficient to account for all the data. 3. Amplitude and rise time were inversely related but the correlation coefficient was very low. For pairs of e.p.s.p.s in the same motoneurone the e.p.s.p. with the fast rise time was larger than that with the slow rise time in forty-eight of sixty-three cases. 4. In a given motoneurone individual e.p.s.p.s evoked by the action of different Ia fibres did not vary greatly in amplitude. The ratio of peak amplitudes was less than 3 for 86% of the pairs of e.p.s.p.s examined, and the maximum was 4-8. 5. Amplitude histograms were constructed for individual e.p.s.p.s at thirty-three synapses. Twenty-two of them could be shown to satisfy the Poisson law. The others satisfied the binomial law or neither. 6. Within a given motoneurone the amplitude of an e.p.s.p. is closely related to the mean number of quanta released but not to the amplitude of the unit e.p.s.p. produced by the action of a single quantum of transmitter."} {"id": "PMID:176356", "title": "Cyclic AMP in sheep ovarian follicles: site of production and response to gonadotrophins.", "content": "This study was undertaken (i) to establish a relationship between cyclic AMP (cAMP) production and the degree of LH and FSH stimulation; (ii) to determine the effects of various gonadotrophins on follicular formation of cAMP; and (iii) to identify the precise intrafollicular site of cAMP formation. The formation of cAMP increased rapidly in follicles exposed to LH. Maximum concentrations were reached after 90 min and were maintained for 180 min. Extracellular release of cAMP increased steadily throughout the 180-min experimental period. Tissue levels of cAMP increased proportionally and significantly when LH concentrations in the medium were increased from 0 to 200 mi.u. ml-1. Tissue levels of cAMP were significantly increased by HCG, prostaglandin E-2 and noradrenaline, but not by prolactin, prostaglandin F-2alpha, serotonin or melatonin. Cyclic AMP formation occurred predominantly in the thecal compartment; the membrana granulosa contributed less than 3% of the total amount of cAMP formed after gonadotrophic stimulation. A significant amount of cAMP from the thecal cells was released into the extracellular compartment and appeared to pass into the granulosa cells.", "contents": "Cyclic AMP in sheep ovarian follicles: site of production and response to gonadotrophins. This study was undertaken (i) to establish a relationship between cyclic AMP (cAMP) production and the degree of LH and FSH stimulation; (ii) to determine the effects of various gonadotrophins on follicular formation of cAMP; and (iii) to identify the precise intrafollicular site of cAMP formation. The formation of cAMP increased rapidly in follicles exposed to LH. Maximum concentrations were reached after 90 min and were maintained for 180 min. Extracellular release of cAMP increased steadily throughout the 180-min experimental period. Tissue levels of cAMP increased proportionally and significantly when LH concentrations in the medium were increased from 0 to 200 mi.u. ml-1. Tissue levels of cAMP were significantly increased by HCG, prostaglandin E-2 and noradrenaline, but not by prolactin, prostaglandin F-2alpha, serotonin or melatonin. Cyclic AMP formation occurred predominantly in the thecal compartment; the membrana granulosa contributed less than 3% of the total amount of cAMP formed after gonadotrophic stimulation. A significant amount of cAMP from the thecal cells was released into the extracellular compartment and appeared to pass into the granulosa cells."} {"id": "PMID:176357", "title": "Effect of LH on the release of cyclic AMP by the rabbit ovary perfused in vivo and in vitro.", "content": "After perfusion of 10 rabbit ovaries in vitro with a modified Krebs bicarbonate buffer containing dextran and glucose, the concentration of cAMP in the perfusion medium was significantly increased 2-5 min after stimulation with 10 mug LH/ml medium and was higher at 15 and 30 min. Intravenous injection of 100 mug LH/rabbit caused a significant increase of cAMP concentrations in the ovarian venous blood from 8 ovaries 10 min after the injection and the cAMP concentrations were higher after 15 and 30 min. The ovarian blood flow was not changed after the LH injection. It is concluded that perfusion techniques can be useful in analysis of the mechanisms and physiological significance of release of cAMP from the ovary after hormonal stimulation.", "contents": "Effect of LH on the release of cyclic AMP by the rabbit ovary perfused in vivo and in vitro. After perfusion of 10 rabbit ovaries in vitro with a modified Krebs bicarbonate buffer containing dextran and glucose, the concentration of cAMP in the perfusion medium was significantly increased 2-5 min after stimulation with 10 mug LH/ml medium and was higher at 15 and 30 min. Intravenous injection of 100 mug LH/rabbit caused a significant increase of cAMP concentrations in the ovarian venous blood from 8 ovaries 10 min after the injection and the cAMP concentrations were higher after 15 and 30 min. The ovarian blood flow was not changed after the LH injection. It is concluded that perfusion techniques can be useful in analysis of the mechanisms and physiological significance of release of cAMP from the ovary after hormonal stimulation."} {"id": "PMID:176358", "title": "Natural estrogen and anti-thrombin III activity in postmenopausal women.", "content": "Anti-thrombin III activity was measured in normal pre- and postmenopausal female controls: during late pregnancy, in young women taking oral contraceptives and in postmenopausal women treated with natural, conjugated estrogens. Both the pregnant patients and women on oral contraceptives had significantly lower anti-thrombin III levels when compared with the normal, untreated control group. Treatment with natural estrogens did not result in any alteration in anti-thrombin III activity. There was no significant difference in the anti-thrombin III values in the pre- and postmenopausal control subjects.", "contents": "Natural estrogen and anti-thrombin III activity in postmenopausal women. Anti-thrombin III activity was measured in normal pre- and postmenopausal female controls: during late pregnancy, in young women taking oral contraceptives and in postmenopausal women treated with natural, conjugated estrogens. Both the pregnant patients and women on oral contraceptives had significantly lower anti-thrombin III levels when compared with the normal, untreated control group. Treatment with natural estrogens did not result in any alteration in anti-thrombin III activity. There was no significant difference in the anti-thrombin III values in the pre- and postmenopausal control subjects."} {"id": "PMID:176359", "title": "Adriamycin analogs. Periodate oxidation of adriamycin.", "content": "Adriamycin is selectively cleaved in high yield at the C13-C14 bond by 1 equiv of sodium metaperiodate to yield carboxylic acid 3. The corresponding methyl ester 4 is obtained by Fischer esterification. Spectral studies indicate that 3 and 4 bind to calf thymus DNA in a manner similar to adriamycin and daunomycin but Tm measurements suggest that less stable complexes are formed. Ester 4 inhibits DNA and RNA synthesis in cultured L1210 cells at levels comparable to adriamycin but acid 3 is much less effective. Both new compounds are moderately effective as antitumor agents against P388 lymphocytic leukemia in the mouse.", "contents": "Adriamycin analogs. Periodate oxidation of adriamycin. Adriamycin is selectively cleaved in high yield at the C13-C14 bond by 1 equiv of sodium metaperiodate to yield carboxylic acid 3. The corresponding methyl ester 4 is obtained by Fischer esterification. Spectral studies indicate that 3 and 4 bind to calf thymus DNA in a manner similar to adriamycin and daunomycin but Tm measurements suggest that less stable complexes are formed. Ester 4 inhibits DNA and RNA synthesis in cultured L1210 cells at levels comparable to adriamycin but acid 3 is much less effective. Both new compounds are moderately effective as antitumor agents against P388 lymphocytic leukemia in the mouse."} {"id": "PMID:176360", "title": "Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism.", "content": "1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were introduced into the 8 position of 2-methyladenosine cyclic 3', 5'-phosphate and 2-butyladenosine cyclic 3', 5'-phosphate by bromination, followed by treatment with sodium benzylmercaptide, sodium p-chlorothiophenolate, or, in the former case, sodium azide. Each of the 1,8- and 2,8-disubstituted derivatives of cAMP was tested as activators of cAMP-dependent protein kinase and as substrates for the inhibitors of cyclic nucleotide phosphodiesterases. Depending on the substitutions, examples were found where the disubstituted derivatives were either more active, equally as active or less active than the monosubstituted parent compounds as protein kinase activators. For the compounds reported, 8-substitution completely or substantially eliminated the ability of 1- or 2-substituted derivatives of cAMP to serve as substrates for phosphodiesterase and diminished the ability of these latter derivatives to inhibit cAMP hydrolysis.", "contents": "Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism. 1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were introduced into the 8 position of 2-methyladenosine cyclic 3', 5'-phosphate and 2-butyladenosine cyclic 3', 5'-phosphate by bromination, followed by treatment with sodium benzylmercaptide, sodium p-chlorothiophenolate, or, in the former case, sodium azide. Each of the 1,8- and 2,8-disubstituted derivatives of cAMP was tested as activators of cAMP-dependent protein kinase and as substrates for the inhibitors of cyclic nucleotide phosphodiesterases. Depending on the substitutions, examples were found where the disubstituted derivatives were either more active, equally as active or less active than the monosubstituted parent compounds as protein kinase activators. For the compounds reported, 8-substitution completely or substantially eliminated the ability of 1- or 2-substituted derivatives of cAMP to serve as substrates for phosphodiesterase and diminished the ability of these latter derivatives to inhibit cAMP hydrolysis."} {"id": "PMID:176361", "title": "Genetic factors in amyloidosis.", "content": "In the absence of biochemical distinctions, the nosography of the inherited amyloidoses must at present depend largely upon clinical subdivisions. In the broad classification adopted here, the disorders have for convenience been grouped according to the anatomical system that is predominantly affected. It is evident that the amyloid syndromes display considerable heterogeneity. However, they overlap. Thus in the Iowa type classified with the hereditary amyloid neuropathies (van Allen et al, 1969; Gimeno et al, 1974), renal involvement was frequent and was the usual cause of death. In the English (Zalin et al, 1974) and Scandinavian (Andersson, 1970) families with neuropathy as the predominant feature, cardiac involvement was a common finding. In certain of the conditions discussed, such as medullary carcinoma of the thyroid and Down's syndrome, amyloid deposition is merely an incidental aspect of the disorder. In those conditions in which generalized or localized amyloid deposition occupies a more central position in the clinical syndrome, an autosomal dominant inheritance has been established or suggested in the majority. An autosomal recessive inheritance has so far only been recognized in familial Mediterranean fever. In the family with hereditary amyloid heart diseases reported by Fredricksen et al (1962), the disorder was confined to a single sibship, raising the possibility of recessive inheritance. This could also be true in sporadic examples of primary amyloidosis. The dominantly inherited amyloidoses comprise a number of geographically widely scattered families with clinical pictures that do not show consistent differences between some families. The families that do not show consistent differences are not necessarily harbouring nutations at the same locus, or the same mutation at any particular locus. However, many of these dominantly inherited clinical syndromes are sufficiently different from each other and the clinical manifestations of each sufficiently consistent to indicate that separate main genes are likely to be involved...", "contents": "Genetic factors in amyloidosis. In the absence of biochemical distinctions, the nosography of the inherited amyloidoses must at present depend largely upon clinical subdivisions. In the broad classification adopted here, the disorders have for convenience been grouped according to the anatomical system that is predominantly affected. It is evident that the amyloid syndromes display considerable heterogeneity. However, they overlap. Thus in the Iowa type classified with the hereditary amyloid neuropathies (van Allen et al, 1969; Gimeno et al, 1974), renal involvement was frequent and was the usual cause of death. In the English (Zalin et al, 1974) and Scandinavian (Andersson, 1970) families with neuropathy as the predominant feature, cardiac involvement was a common finding. In certain of the conditions discussed, such as medullary carcinoma of the thyroid and Down's syndrome, amyloid deposition is merely an incidental aspect of the disorder. In those conditions in which generalized or localized amyloid deposition occupies a more central position in the clinical syndrome, an autosomal dominant inheritance has been established or suggested in the majority. An autosomal recessive inheritance has so far only been recognized in familial Mediterranean fever. In the family with hereditary amyloid heart diseases reported by Fredricksen et al (1962), the disorder was confined to a single sibship, raising the possibility of recessive inheritance. This could also be true in sporadic examples of primary amyloidosis. The dominantly inherited amyloidoses comprise a number of geographically widely scattered families with clinical pictures that do not show consistent differences between some families. The families that do not show consistent differences are not necessarily harbouring nutations at the same locus, or the same mutation at any particular locus. However, many of these dominantly inherited clinical syndromes are sufficiently different from each other and the clinical manifestations of each sufficiently consistent to indicate that separate main genes are likely to be involved..."} {"id": "PMID:176363", "title": "Control of the uptake of amino acids by serum chick embryo cells, untransformed or transformed rous sarcoma virus.", "content": "Forty to fifty minutes after removal of serum, the net total uptake of amino acids in growing secondary cultures of normal or virus-transformed chick embryo cells, stopped or proceeded only at a highly reduced rate. In both normal and transformed cells, the initial (0-40 min) rate of the above uptake was the same in the absence of serum as in its presence. The initial rate of the total uptake of amino acids in growing transformed cells was about the same as in growing normal cells. Neither in the normal nor in the transformed cells was the rate of the total uptake of amino acids reduced by cell confluence alone. In highly dense, hyperconfluent cultures of normal cells in which cell growth was arrested, the rate of uptake in the absence or in the presence of serum was four- to fivefold lower than the rate obtained in growing normal cells under similar conditions; in the absence of serum, the net uptake stopped after 40 min in the hyperconfluent cultures as well. It appears that cells growing in tissue culture require a serum factor for maintenance of the required high rates of uptake of amino acids and that the inhibition of growth at high cell densities is a result of depletion of this factor from serum, or the inability of the cells in a dense culture to respond to the factor. A serum factor is apparently also required for maintenance of the reduced rates of uptake of amino acids observed in hyperconfluent cultures.", "contents": "Control of the uptake of amino acids by serum chick embryo cells, untransformed or transformed rous sarcoma virus. Forty to fifty minutes after removal of serum, the net total uptake of amino acids in growing secondary cultures of normal or virus-transformed chick embryo cells, stopped or proceeded only at a highly reduced rate. In both normal and transformed cells, the initial (0-40 min) rate of the above uptake was the same in the absence of serum as in its presence. The initial rate of the total uptake of amino acids in growing transformed cells was about the same as in growing normal cells. Neither in the normal nor in the transformed cells was the rate of the total uptake of amino acids reduced by cell confluence alone. In highly dense, hyperconfluent cultures of normal cells in which cell growth was arrested, the rate of uptake in the absence or in the presence of serum was four- to fivefold lower than the rate obtained in growing normal cells under similar conditions; in the absence of serum, the net uptake stopped after 40 min in the hyperconfluent cultures as well. It appears that cells growing in tissue culture require a serum factor for maintenance of the required high rates of uptake of amino acids and that the inhibition of growth at high cell densities is a result of depletion of this factor from serum, or the inability of the cells in a dense culture to respond to the factor. A serum factor is apparently also required for maintenance of the reduced rates of uptake of amino acids observed in hyperconfluent cultures."} {"id": "PMID:176364", "title": "Study of enzymes regulating vasopressin-stimulated cyclic AMP metabolism in separated mitochondria-rich and granular epithelial cells of toad urinary bladder.", "content": "The epithelial cells of the toad urinary bladder are morphologically heterogenous. In order to relate the effect of vasopressin on cyclic AMP metabolism to cell type, the epithelial cells were separated by the density gradient technique of Scott, Sapirstein and Yoder (Science 184:797, 1974). The separation was verified by electron-microscopy and by observing that the band of cells enriched in mitochondria-rich cells was enriched in carbonic anhydrase activity compared to the band of granular cells. A large portion of cells collected from the gradient was considered to be nonviable, precluding further study of their function as intact cells. Vasopressin-stimulated adenylate cyclase activity in homogenates of granular cells was simular to that in homogenates of mitochondria-rich cells. Cyclic nucleotide phosphodiesterase activity was also similar in the two types of cell. Thus, the enzymes known to be involved in cyclic AMP metabolism in response to vasopressin appear to be located in both major cell types.", "contents": "Study of enzymes regulating vasopressin-stimulated cyclic AMP metabolism in separated mitochondria-rich and granular epithelial cells of toad urinary bladder. The epithelial cells of the toad urinary bladder are morphologically heterogenous. In order to relate the effect of vasopressin on cyclic AMP metabolism to cell type, the epithelial cells were separated by the density gradient technique of Scott, Sapirstein and Yoder (Science 184:797, 1974). The separation was verified by electron-microscopy and by observing that the band of cells enriched in mitochondria-rich cells was enriched in carbonic anhydrase activity compared to the band of granular cells. A large portion of cells collected from the gradient was considered to be nonviable, precluding further study of their function as intact cells. Vasopressin-stimulated adenylate cyclase activity in homogenates of granular cells was simular to that in homogenates of mitochondria-rich cells. Cyclic nucleotide phosphodiesterase activity was also similar in the two types of cell. Thus, the enzymes known to be involved in cyclic AMP metabolism in response to vasopressin appear to be located in both major cell types."} {"id": "PMID:176362", "title": "Selective inhibition of urea transport by oxidizing agents. Evidence for a site of inhibition behond the generation of cyclic AMP.", "content": "Urea and water transport across the toad bladder epithelial cell appears to take place through independent vasopressin-stimulated pathways. Agents such as chromate, for example, when added to the luminal bathing medium, inhibit urea transport without inhibiting osmotic water flow, providing evidence for such independent pathways. In the present study, selective inhibition of urea transport is shown for permanganate and methylene blue, which like chromate, are oxidizing agents. Permanganate inhibits urea transport irreversibly, while methylene blue acts reversibly. Not all oxidizing agents are inhibitory; perchlorate, peroxide and ferricyanide have no effect on urea transport or water flow. Permanganate and chromate both act at a point beyond the generation of cyclic AMP, since they continue to inhibit urea transport in bladders treated with exogenous cyclic AMP, 8-bromoadenosine 3', 5'-cyclic monophosphate, and a combination of cyclic AMP and theophylline. These findings suggest that selective inhibition of urea transport can be brought about by oxidation of one or more components in its transport pathway, and that, in the case of chromate and permanganate, these components may be in the luminal membrane itself.", "contents": "Selective inhibition of urea transport by oxidizing agents. Evidence for a site of inhibition behond the generation of cyclic AMP. Urea and water transport across the toad bladder epithelial cell appears to take place through independent vasopressin-stimulated pathways. Agents such as chromate, for example, when added to the luminal bathing medium, inhibit urea transport without inhibiting osmotic water flow, providing evidence for such independent pathways. In the present study, selective inhibition of urea transport is shown for permanganate and methylene blue, which like chromate, are oxidizing agents. Permanganate inhibits urea transport irreversibly, while methylene blue acts reversibly. Not all oxidizing agents are inhibitory; perchlorate, peroxide and ferricyanide have no effect on urea transport or water flow. Permanganate and chromate both act at a point beyond the generation of cyclic AMP, since they continue to inhibit urea transport in bladders treated with exogenous cyclic AMP, 8-bromoadenosine 3', 5'-cyclic monophosphate, and a combination of cyclic AMP and theophylline. These findings suggest that selective inhibition of urea transport can be brought about by oxidation of one or more components in its transport pathway, and that, in the case of chromate and permanganate, these components may be in the luminal membrane itself."} {"id": "PMID:176373", "title": "Characterization of mouse mammary tumor viruses from primary tumor cell cultures.I. Immunologic and structural studies.", "content": "Primary cell cultures of mammary tumors from Rill, GR, DD, BALB/cfC3H, and BALB/c mice were prepared by trypsin-EDTA dissociation of tumors. Cultures from these strains contained predominantly cells of epithelial morphology which formed three-dimensional domelike structures. Cultures from Rill, GR, DD, and BALB/cfC3H tumors produced extra-cellular type-B mouse mammary tumor virus(es) (MuMTV), either in the absence of detectable type-C virus or with less than 1% contamination with type-C virus. This was determined by radioimmunoassays for MuMTV and murine leukemia virus (MuLV) antigens. Only BALB/c cultures produced MuMTV with as much as 3% contaminating MuLV. High levels of MuMTV surface antigen were also found in soluble form in culture supernatants. Virus polypeptide analyses by electrophoresis on polyacrylamide gels showed that the Rill BALB/cfC3H, DD, and BALB/c viruses all contained polypeptides characteristic of MuMTV. Primary cultures of mammary tumor cells make available a source of purified MuMTV antigens, structural proteins, and nucleic acids for comparative studies of MuMTV from various mouse strains.", "contents": "Characterization of mouse mammary tumor viruses from primary tumor cell cultures.I. Immunologic and structural studies. Primary cell cultures of mammary tumors from Rill, GR, DD, BALB/cfC3H, and BALB/c mice were prepared by trypsin-EDTA dissociation of tumors. Cultures from these strains contained predominantly cells of epithelial morphology which formed three-dimensional domelike structures. Cultures from Rill, GR, DD, and BALB/cfC3H tumors produced extra-cellular type-B mouse mammary tumor virus(es) (MuMTV), either in the absence of detectable type-C virus or with less than 1% contamination with type-C virus. This was determined by radioimmunoassays for MuMTV and murine leukemia virus (MuLV) antigens. Only BALB/c cultures produced MuMTV with as much as 3% contaminating MuLV. High levels of MuMTV surface antigen were also found in soluble form in culture supernatants. Virus polypeptide analyses by electrophoresis on polyacrylamide gels showed that the Rill BALB/cfC3H, DD, and BALB/c viruses all contained polypeptides characteristic of MuMTV. Primary cultures of mammary tumor cells make available a source of purified MuMTV antigens, structural proteins, and nucleic acids for comparative studies of MuMTV from various mouse strains."} {"id": "PMID:176374", "title": "Characterization of mouse mammary tumor viruses from primary tumor cell cultures. II. Biochemical and biophysical studies.", "content": "Primary mammary tumor cultures of RIII, GR, DD, BALB/c, and BALB/cfC3H mice were examined for mouse mammary tumor virus (MuMTV) production. Levels of production of 12-32 mug virus protein/day/75-cm2 culture flask could be maintained for 30-50 days with daily virus harvests. The viruses from tumor cell cultures of these mouse strains contained DNA polymerase with a strong preference for Mg++ over Mn++ as the divalent cation, a characteristic of DNA polymerase of MuMTV from mouse milk. These viruses from tumor cell cultures were excellent sources of MuMTV 3H-complementary DNA (complexed to 60-70S RNA) and radioactive 60-70S RNA, sufficiently free of contaminating murine leukemia virus nucleic acids, that can be used in molecular hybridization experiments. The effects of several culture parameters on MuMTV production were also studied.", "contents": "Characterization of mouse mammary tumor viruses from primary tumor cell cultures. II. Biochemical and biophysical studies. Primary mammary tumor cultures of RIII, GR, DD, BALB/c, and BALB/cfC3H mice were examined for mouse mammary tumor virus (MuMTV) production. Levels of production of 12-32 mug virus protein/day/75-cm2 culture flask could be maintained for 30-50 days with daily virus harvests. The viruses from tumor cell cultures of these mouse strains contained DNA polymerase with a strong preference for Mg++ over Mn++ as the divalent cation, a characteristic of DNA polymerase of MuMTV from mouse milk. These viruses from tumor cell cultures were excellent sources of MuMTV 3H-complementary DNA (complexed to 60-70S RNA) and radioactive 60-70S RNA, sufficiently free of contaminating murine leukemia virus nucleic acids, that can be used in molecular hybridization experiments. The effects of several culture parameters on MuMTV production were also studied."} {"id": "PMID:176375", "title": "A murine Wilms' tumor as a model for chemotherapy and radiotherapy.", "content": "We studied the effect on tumor volumes and host survival of twenty-four chemotherapeutic and radiotherapeutic regimens in rats bearing the Furth/Columbia murine Wilms' tumor. After 5 years and some 100 transfers, this tumor retained its sensitivity to suitable combinations of actinomycin D, vincristine, and X-ray, regimens in current use in the treatment of human Wilms' tumor. Cytoxan alone was highly inhibitory; adriamycin was modestly inhibitory; and lethal doses of methotrexate followed by leucovorin \"rescue\" were slightly inhibitory to the growth of the rat tumor. No other chemotherapeutic agent tested was effective by our criteria. Cytoxan, with or without adriamycin, and X-irradiation, were the most useful combinations studied. The chemotherapeutic agents given 3 days before irradiation were significantly more carcinostatic than they were when given after radiotherapy.", "contents": "A murine Wilms' tumor as a model for chemotherapy and radiotherapy. We studied the effect on tumor volumes and host survival of twenty-four chemotherapeutic and radiotherapeutic regimens in rats bearing the Furth/Columbia murine Wilms' tumor. After 5 years and some 100 transfers, this tumor retained its sensitivity to suitable combinations of actinomycin D, vincristine, and X-ray, regimens in current use in the treatment of human Wilms' tumor. Cytoxan alone was highly inhibitory; adriamycin was modestly inhibitory; and lethal doses of methotrexate followed by leucovorin \"rescue\" were slightly inhibitory to the growth of the rat tumor. No other chemotherapeutic agent tested was effective by our criteria. Cytoxan, with or without adriamycin, and X-irradiation, were the most useful combinations studied. The chemotherapeutic agents given 3 days before irradiation were significantly more carcinostatic than they were when given after radiotherapy."} {"id": "PMID:176376", "title": "Airborne transmission of polyoma virus.", "content": "Polyoma virus (PV) infection was transmitted through the air of an animal laboratory. Mice free of detectable antibodies to PV were exposed for 1 month to the airborne environment of laboratories housing naturally infected mice. The seroconversion rate was 75% (24/32), as measured by hemagglutination inhibition. Control mice, housed in the sterile atmosphere of a mass air flow cabinet (MAFC) in the same laboratory, had a seroconversion rate of 15.8% (3/19). Airborne transmission occurred bia PV aerosois, generated by the handling of contaminated bedding, cages, and mice during weekly housekeeping. Length of exposure to PV aerosols correlated with seroconversion. One- and 3-hour exposures resulted in seroconversion rates of 40% (6/15) and 72% (23/32), respectively. Seroconversion rates of mice continuously housed in MAFC totaled 5% (2/40). Checkerboarding mice free of detectable antibodies with mice given 10(5) mean tissue culture infective doses of PV ip resulted in an airborne infection rate of 50% (15/30) in a conventionally ventilated room during a 12-week study. The airborne transmission rate was 10% (3/30) when experiments were performed in a mass air flow room with a vertical air velocity of 30 feet/minute was used. Antibodies to PV could not be detected in any of 138 human sera, including sera from 29 animal-care technicians who handled PV-infected mice and 15 personnel who had worked with the virus.", "contents": "Airborne transmission of polyoma virus. Polyoma virus (PV) infection was transmitted through the air of an animal laboratory. Mice free of detectable antibodies to PV were exposed for 1 month to the airborne environment of laboratories housing naturally infected mice. The seroconversion rate was 75% (24/32), as measured by hemagglutination inhibition. Control mice, housed in the sterile atmosphere of a mass air flow cabinet (MAFC) in the same laboratory, had a seroconversion rate of 15.8% (3/19). Airborne transmission occurred bia PV aerosois, generated by the handling of contaminated bedding, cages, and mice during weekly housekeeping. Length of exposure to PV aerosols correlated with seroconversion. One- and 3-hour exposures resulted in seroconversion rates of 40% (6/15) and 72% (23/32), respectively. Seroconversion rates of mice continuously housed in MAFC totaled 5% (2/40). Checkerboarding mice free of detectable antibodies with mice given 10(5) mean tissue culture infective doses of PV ip resulted in an airborne infection rate of 50% (15/30) in a conventionally ventilated room during a 12-week study. The airborne transmission rate was 10% (3/30) when experiments were performed in a mass air flow room with a vertical air velocity of 30 feet/minute was used. Antibodies to PV could not be detected in any of 138 human sera, including sera from 29 animal-care technicians who handled PV-infected mice and 15 personnel who had worked with the virus."} {"id": "PMID:176377", "title": "Growth in semisolid agar medium of human cord leukocytes freshly transformed by Epstein-Barr virus.", "content": "The semisolid agar method for the selective growth of transformed cells was applied to investigations of Epstein-Barr virus (EBV) transformation. When 1 X 10(5) HUMAn umbilical-cord blood leukocytes were seeded in agar medium immediately after EBV exposure, about 100 colonies developed in each dish. The occurrence of colonies correlated well with dilutions of EBV inoculum. These colonies were composed of lymphoblasts, were positive for EBV-determined nuclear antigen immunofluorescence, and consistently resulted in the establishment of cell lines. In cord leukocyte cultures exposed to EBV, cells capable of growing in semisolid agar medium appeared early and increased rapidly, though the total numbers of leukocytes and control cultures decreased during the first several days.", "contents": "Growth in semisolid agar medium of human cord leukocytes freshly transformed by Epstein-Barr virus. The semisolid agar method for the selective growth of transformed cells was applied to investigations of Epstein-Barr virus (EBV) transformation. When 1 X 10(5) HUMAn umbilical-cord blood leukocytes were seeded in agar medium immediately after EBV exposure, about 100 colonies developed in each dish. The occurrence of colonies correlated well with dilutions of EBV inoculum. These colonies were composed of lymphoblasts, were positive for EBV-determined nuclear antigen immunofluorescence, and consistently resulted in the establishment of cell lines. In cord leukocyte cultures exposed to EBV, cells capable of growing in semisolid agar medium appeared early and increased rapidly, though the total numbers of leukocytes and control cultures decreased during the first several days."} {"id": "PMID:176378", "title": "Stimulatory effect of 3', 5'-adenosine monophosphate on protein synthesis in heat-shocked murine leukemia lymphoblasts.", "content": "The murine leukemia lymphoblast line L5178Y was tested for its early molecular response to the presence of dibutyryl cyclic AMP. Protein synthesis was reversibly inhibited by short durations of hyperthermia, and against this reduced background of protein synthetic activity, early leucine incorporation (30-120 min) was markedly and consistently stimulated by the presence of the cyclic nucleotide. The effect became one of inhibition with extended times of incubation (longer than 120 min).", "contents": "Stimulatory effect of 3', 5'-adenosine monophosphate on protein synthesis in heat-shocked murine leukemia lymphoblasts. The murine leukemia lymphoblast line L5178Y was tested for its early molecular response to the presence of dibutyryl cyclic AMP. Protein synthesis was reversibly inhibited by short durations of hyperthermia, and against this reduced background of protein synthetic activity, early leucine incorporation (30-120 min) was markedly and consistently stimulated by the presence of the cyclic nucleotide. The effect became one of inhibition with extended times of incubation (longer than 120 min)."} {"id": "PMID:176379", "title": "Genetic analysis of mammary tumor induction and expression of mammary tumor virus antigen in hormone-treated ovariectomized GR mice.", "content": "Early stages of mammary tumors (EMT) were induced with a combined treatment of progesterone (P) and estrone (E) in ovariectomized adult GRS/A (GR) mice, a strain of European origin and with a high incidence of mammary cancer. The mammary tumors were comparable to the pregnancy-dependent tumors of breeding females of this strain. The hormone treatment did not lead to EMT in a variety of other strains and only occasionally in the RIII an C3H strains. Treatment with P or E alone di not lead to EMT in GR mice, but treatment with the steroid compound 17 alpha-ethynyl-19-nortestosterone (ANT) did mimic the combined effe(t of P and E. Since EMT could be induced by ANT in all ovariectomized adult GR mice within 3 weeks, this tumor-induction method was suitable for analysis of the gene responsible for palpable, pregnancy-dependent mammary tumors of this strain. Another argument for the usefulness of this test for genetic analysis was the fact that, though mouse mammary tumor virus (MuMTV) of the GR strain was introduced into BALB/c and tmas mice by foster-nursing, ANT treatment did not lead to EMT. First and second backcross analyses showed that one gene was responsible for EMT induction. There was a strong (orrelation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf. This suggested that the expression of MuMTV antigens was also controlled by the EMT gene. Two types of resistance phenomena were observed. Neither type could prevent EMT after hormone treatment; however, they could delay EMT development. One resistance factor for EMT induction was noticeable and dominant in reciprocal hybrids of the GR and DBAf strains, whereas another resistance factor was detected in the backcross population only [i.e., in the C57BL X (C57BL X Gr) ba(kcross] and not in hybrids; therefore, this factor was recessive. Until now, linkage experiments with 18 markers to locate the gene for EMT induction in the map of the mouse were unsuccessful.", "contents": "Genetic analysis of mammary tumor induction and expression of mammary tumor virus antigen in hormone-treated ovariectomized GR mice. Early stages of mammary tumors (EMT) were induced with a combined treatment of progesterone (P) and estrone (E) in ovariectomized adult GRS/A (GR) mice, a strain of European origin and with a high incidence of mammary cancer. The mammary tumors were comparable to the pregnancy-dependent tumors of breeding females of this strain. The hormone treatment did not lead to EMT in a variety of other strains and only occasionally in the RIII an C3H strains. Treatment with P or E alone di not lead to EMT in GR mice, but treatment with the steroid compound 17 alpha-ethynyl-19-nortestosterone (ANT) did mimic the combined effe(t of P and E. Since EMT could be induced by ANT in all ovariectomized adult GR mice within 3 weeks, this tumor-induction method was suitable for analysis of the gene responsible for palpable, pregnancy-dependent mammary tumors of this strain. Another argument for the usefulness of this test for genetic analysis was the fact that, though mouse mammary tumor virus (MuMTV) of the GR strain was introduced into BALB/c and tmas mice by foster-nursing, ANT treatment did not lead to EMT. First and second backcross analyses showed that one gene was responsible for EMT induction. There was a strong (orrelation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf. This suggested that the expression of MuMTV antigens was also controlled by the EMT gene. Two types of resistance phenomena were observed. Neither type could prevent EMT after hormone treatment; however, they could delay EMT development. One resistance factor for EMT induction was noticeable and dominant in reciprocal hybrids of the GR and DBAf strains, whereas another resistance factor was detected in the backcross population only [i.e., in the C57BL X (C57BL X Gr) ba(kcross] and not in hybrids; therefore, this factor was recessive. Until now, linkage experiments with 18 markers to locate the gene for EMT induction in the map of the mouse were unsuccessful."} {"id": "PMID:176380", "title": "Amount of satellite DNA in four experimentally induced tumors of the central nervous system. Quantitative changes in a glioblastoma producing C-type particles.", "content": "The quantitative preservation of satellite NA was studied in several central nervous system (CNS) neoplasms; four tumor lines deriveo from 3-methylcholanthrene implantation into the CNS of mice were compared with brain and tissue cultures of normal mouse cells by analytical centrifugation in cesium chlorie. Three tumors showed no detectable difference from normal cells; nuclear and whole cell preparations were comparable. Only a glioblastoma line proucing C-type particles (TC509) revealed a significant difference from normal cells and exhibited a decrease of approximately 20% in satellite DNA or 2% of the total DNA on repeated examination for 1 year. C-type RNA virus may be related to relative decreases in satellite DNA observed in TC509.", "contents": "Amount of satellite DNA in four experimentally induced tumors of the central nervous system. Quantitative changes in a glioblastoma producing C-type particles. The quantitative preservation of satellite NA was studied in several central nervous system (CNS) neoplasms; four tumor lines deriveo from 3-methylcholanthrene implantation into the CNS of mice were compared with brain and tissue cultures of normal mouse cells by analytical centrifugation in cesium chlorie. Three tumors showed no detectable difference from normal cells; nuclear and whole cell preparations were comparable. Only a glioblastoma line proucing C-type particles (TC509) revealed a significant difference from normal cells and exhibited a decrease of approximately 20% in satellite DNA or 2% of the total DNA on repeated examination for 1 year. C-type RNA virus may be related to relative decreases in satellite DNA observed in TC509."} {"id": "PMID:176381", "title": "Development of a lymphocyte transformation microassay for murine leukemia virus.", "content": "A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweek mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 mug during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cell infected with MuLV.", "contents": "Development of a lymphocyte transformation microassay for murine leukemia virus. A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweek mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 mug during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cell infected with MuLV."} {"id": "PMID:176382", "title": "Biochemical studies on mitochondria isolated from Normal and Neoplastic Tissues of the Mouse Mammary Gland.", "content": "Mitochondria isolated from spontaneous and transplanted mammary adenocarcinomas of two strains of mice were compared, by various biochemical criteria, to mitochondria from mammary glands of midpregnant or hormonally stimulated, cancer-free mice. The specific activities of several mitochondrial enzymes including cytochrome oxidase, alpha-glycerophosphate oxidase, and succinate dehydrogenase were twofold to threefold lower, whereas the activity of monoamine oxidase was two fold higher in tumor mitochondria. Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria. In addition, mitochondrial polypeptide composition was analyzed by electrophoresis on sodium dodecyl sulfate-urea polyacrylamide gels. Midpregnant mammary gland and mammary tumor mitochondria were similar in polypeptide composition; however, several differences were observed. A high-molecular-weight polypeptide, present in mid-pregnant mammary gland mitochondria was absent from tumor mitochondria. Also, tumor mitochondria contained an additional high-molecular-weight polypeptide not found in the midpregnant mammary gland. There were numerous differences in the relative proportions of many polypeptides common to both tumor and midpregnant mammary gland mitochondria.", "contents": "Biochemical studies on mitochondria isolated from Normal and Neoplastic Tissues of the Mouse Mammary Gland. Mitochondria isolated from spontaneous and transplanted mammary adenocarcinomas of two strains of mice were compared, by various biochemical criteria, to mitochondria from mammary glands of midpregnant or hormonally stimulated, cancer-free mice. The specific activities of several mitochondrial enzymes including cytochrome oxidase, alpha-glycerophosphate oxidase, and succinate dehydrogenase were twofold to threefold lower, whereas the activity of monoamine oxidase was two fold higher in tumor mitochondria. Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria. In addition, mitochondrial polypeptide composition was analyzed by electrophoresis on sodium dodecyl sulfate-urea polyacrylamide gels. Midpregnant mammary gland and mammary tumor mitochondria were similar in polypeptide composition; however, several differences were observed. A high-molecular-weight polypeptide, present in mid-pregnant mammary gland mitochondria was absent from tumor mitochondria. Also, tumor mitochondria contained an additional high-molecular-weight polypeptide not found in the midpregnant mammary gland. There were numerous differences in the relative proportions of many polypeptides common to both tumor and midpregnant mammary gland mitochondria."} {"id": "PMID:176383", "title": "Reexpression of the original tumor pattern by a human breast carcinoma cell line (MCF-7) in sponge culture.", "content": "A stable cell line (MCF-7), derived from a pleural effusion of a patient with metastatic breast carcinoma, was maintained in these laboratories for more than 3 years in conventional monolayer culture. To further characterize the tumor origin of the MCF-7 line, cells were grown on collagen-coated cellulos sponges. On the three-dimensional sponge matrix, the cells formed clusters, ductlike structures, and lumina similar to the patterns observed in the antecedent primary tumor and in the pleural metastasis. The similarity between the original tumor and the cells grown in sponge suggested that the MCF-7 cells did in fact retain the potential to express the histologic patterns of tumor, even in the absence of stroma support. This study confirmed the utility of sponge culture for the investigation of the retention of tumor characteristics by cultured cells of neoplastic origin.", "contents": "Reexpression of the original tumor pattern by a human breast carcinoma cell line (MCF-7) in sponge culture. A stable cell line (MCF-7), derived from a pleural effusion of a patient with metastatic breast carcinoma, was maintained in these laboratories for more than 3 years in conventional monolayer culture. To further characterize the tumor origin of the MCF-7 line, cells were grown on collagen-coated cellulos sponges. On the three-dimensional sponge matrix, the cells formed clusters, ductlike structures, and lumina similar to the patterns observed in the antecedent primary tumor and in the pleural metastasis. The similarity between the original tumor and the cells grown in sponge suggested that the MCF-7 cells did in fact retain the potential to express the histologic patterns of tumor, even in the absence of stroma support. This study confirmed the utility of sponge culture for the investigation of the retention of tumor characteristics by cultured cells of neoplastic origin."} {"id": "PMID:176384", "title": "Specificity of human antibodies to intracytoplasmic type-A particles of the murine mammary tumor virus.", "content": "Large-scale studies showed that antibodies previously detectable in women with proliferating mastopathy or breast cancer were directed to intracytoplasmic type-A particles (iAp) of mouse mammary tumor virus. Immunofluorescence revealed the human antibodies to be bound only by those tumors producing a certain amount of iAp clusters visible by light microscopy. The intensity of the reaction corresponded to the iAp content of every tumor tested as revealed by electron microscopy and rabbit antisera to iAp. The fluorescence patterns obtained with positive human sera were similar to those obtained with rabbit antisera specific for iAp and resembled the tissue distribution patterns of iAp inclusions stained by acid fuchsin. The reaction with human sera was entirely blocked by rabbit antisera to iAp and, less so, by rabbit or mouse antisera to B particles. The human antibody activity was exhaustively absorbed by purified iAp or purified and disrupted B particles, which indicated that the human antibodies were directed to antigenic components shared by iAp and B particles. Preliminary immunoperoxidase studies supported the assumption that the human antibodies were bound to the iAp membrane; technical details might have accounted for the finding that the human antibodies reacted with the iAp but not with B particles in situ.", "contents": "Specificity of human antibodies to intracytoplasmic type-A particles of the murine mammary tumor virus. Large-scale studies showed that antibodies previously detectable in women with proliferating mastopathy or breast cancer were directed to intracytoplasmic type-A particles (iAp) of mouse mammary tumor virus. Immunofluorescence revealed the human antibodies to be bound only by those tumors producing a certain amount of iAp clusters visible by light microscopy. The intensity of the reaction corresponded to the iAp content of every tumor tested as revealed by electron microscopy and rabbit antisera to iAp. The fluorescence patterns obtained with positive human sera were similar to those obtained with rabbit antisera specific for iAp and resembled the tissue distribution patterns of iAp inclusions stained by acid fuchsin. The reaction with human sera was entirely blocked by rabbit antisera to iAp and, less so, by rabbit or mouse antisera to B particles. The human antibody activity was exhaustively absorbed by purified iAp or purified and disrupted B particles, which indicated that the human antibodies were directed to antigenic components shared by iAp and B particles. Preliminary immunoperoxidase studies supported the assumption that the human antibodies were bound to the iAp membrane; technical details might have accounted for the finding that the human antibodies reacted with the iAp but not with B particles in situ."} {"id": "PMID:176385", "title": "Limitation of multinucleation by dibutyryl adenosine 3',5'-cyclic monophosphate in tumor cells treated with cytochalasin B.", "content": "Hamster BHK21 tumor cells and human rhabdomyosarcoma (RD) cells responded to cytochalasin B (CB) by becoming highly multinucleated. Nearly 80% of the BHK cells contained four or more nuclei after 7 days of exposure to CB, and 35% of these had at least seven nuclei. Similar frequencies of multinucleation were obtained with RD cells. Administration of 10(-3) M theophylline and dibutyryl adenosine 3',5'-cyclic monophosphate (Bu2cAMP) at 5X10(-4) M or 10(-3) M to CB-treated RD or BHK cells greatly reduced the frequency of cells with five or more nuclei. The frequency of cells with seven or more nuclei was reduced to less than 5%. Along with this reduction in highly multinucleated cells was an increase in the incidence of binucleated cells. Bu2cAMP was toxic and caused many CB-treated BHK cells to detach from the culture surface, but not all cells were killed. Bu2cAMP had little toxic effect on CB-treated RD cells. These observations indicated that the inhibition of high degrees of multinucleation were not the result of nonspecific toxic effects of Bu2cAMP but that nuclear division was limited by it. The effect of Bu2cAMP on density-dependent inhibition of growth was also studied. Addition of only theophylline and Bu2cAMP to either BHK or RD cells resulted in growth to significantly lower saturation densities. The toxicity of Bu2cAMP on cells in crowded cultures apparently caused the limited propagation. Bu2cAMP resulted in significant cell killing or detachment but, once the lower saturation densities were reached, cell death was minimized. Thus Bu2cAMP did not restore contact inhibition per se. It was also found that untreated RD cells grew to lower concentration densities than expected from the microscopic inspection of cells in situ. Microscopic inspection revealed high concentration densities and numerous mitoses. This apparent contradiction was due to the ability of RD cells to fuse upon the attainment of confluence and to produce multinucleated cells without the aid of CB.", "contents": "Limitation of multinucleation by dibutyryl adenosine 3',5'-cyclic monophosphate in tumor cells treated with cytochalasin B. Hamster BHK21 tumor cells and human rhabdomyosarcoma (RD) cells responded to cytochalasin B (CB) by becoming highly multinucleated. Nearly 80% of the BHK cells contained four or more nuclei after 7 days of exposure to CB, and 35% of these had at least seven nuclei. Similar frequencies of multinucleation were obtained with RD cells. Administration of 10(-3) M theophylline and dibutyryl adenosine 3',5'-cyclic monophosphate (Bu2cAMP) at 5X10(-4) M or 10(-3) M to CB-treated RD or BHK cells greatly reduced the frequency of cells with five or more nuclei. The frequency of cells with seven or more nuclei was reduced to less than 5%. Along with this reduction in highly multinucleated cells was an increase in the incidence of binucleated cells. Bu2cAMP was toxic and caused many CB-treated BHK cells to detach from the culture surface, but not all cells were killed. Bu2cAMP had little toxic effect on CB-treated RD cells. These observations indicated that the inhibition of high degrees of multinucleation were not the result of nonspecific toxic effects of Bu2cAMP but that nuclear division was limited by it. The effect of Bu2cAMP on density-dependent inhibition of growth was also studied. Addition of only theophylline and Bu2cAMP to either BHK or RD cells resulted in growth to significantly lower saturation densities. The toxicity of Bu2cAMP on cells in crowded cultures apparently caused the limited propagation. Bu2cAMP resulted in significant cell killing or detachment but, once the lower saturation densities were reached, cell death was minimized. Thus Bu2cAMP did not restore contact inhibition per se. It was also found that untreated RD cells grew to lower concentration densities than expected from the microscopic inspection of cells in situ. Microscopic inspection revealed high concentration densities and numerous mitoses. This apparent contradiction was due to the ability of RD cells to fuse upon the attainment of confluence and to produce multinucleated cells without the aid of CB."} {"id": "PMID:176386", "title": "Antibody response to related leukosis viruses induced in chickens tolerant to an avian leukosis virus.", "content": "White Leghorn chickens congenitally infected with a subgroup A avian leukosis virus ALV-F42 were challenged at various ages with the serologically related subgroup A avian leukosis viruses (ALV) RAV-1, RAV-3, and RAV-5 and their antibody responses and viremic status determined. Birds given injections of RAV-1 failed to produce neutralizing antibody to any of the pseudotype sarcoma viruses of the various ALV, whereas many birds challenged with RAV-3 or RAV-5 produced neutralizing antibody directed against the heterologous RAV-1 as well as the homologous viruses, but not against the tolerated virus ALV-F42. Virtually all birds remained viremic despite the presence of neutralizing antibody. The results suggested that a phenomenon akin to circumvention or abrogation of tolerance to ALV-F42 was effected, and that there are multiple determinants of the viral envelope antigens of ALV as measured by neutralization.", "contents": "Antibody response to related leukosis viruses induced in chickens tolerant to an avian leukosis virus. White Leghorn chickens congenitally infected with a subgroup A avian leukosis virus ALV-F42 were challenged at various ages with the serologically related subgroup A avian leukosis viruses (ALV) RAV-1, RAV-3, and RAV-5 and their antibody responses and viremic status determined. Birds given injections of RAV-1 failed to produce neutralizing antibody to any of the pseudotype sarcoma viruses of the various ALV, whereas many birds challenged with RAV-3 or RAV-5 produced neutralizing antibody directed against the heterologous RAV-1 as well as the homologous viruses, but not against the tolerated virus ALV-F42. Virtually all birds remained viremic despite the presence of neutralizing antibody. The results suggested that a phenomenon akin to circumvention or abrogation of tolerance to ALV-F42 was effected, and that there are multiple determinants of the viral envelope antigens of ALV as measured by neutralization."} {"id": "PMID:176387", "title": "Growth suppression of subcutaneously inoculated hepatic tumors after injection of syngeneic liver cells into the subcutaneous tissue of rats.", "content": "One week after the sc injection of minced tissues of the livers, kidneys, or spleens of W, Donryu, and MP rats into the left back of syngeneic rats, ascites-type tumor cells derived from rat hepatoma (AH 130) or Walker carcinosarcoma cells derived from rat breast tumor were inoculated sc into the right back. Ascites hepatoma cell growth was slowest in the group given the liver preparation, whereas no significant difference was noted in the growth of Walker carcinosarcoma in all groups. The results were similar in all strains.", "contents": "Growth suppression of subcutaneously inoculated hepatic tumors after injection of syngeneic liver cells into the subcutaneous tissue of rats. One week after the sc injection of minced tissues of the livers, kidneys, or spleens of W, Donryu, and MP rats into the left back of syngeneic rats, ascites-type tumor cells derived from rat hepatoma (AH 130) or Walker carcinosarcoma cells derived from rat breast tumor were inoculated sc into the right back. Ascites hepatoma cell growth was slowest in the group given the liver preparation, whereas no significant difference was noted in the growth of Walker carcinosarcoma in all groups. The results were similar in all strains."} {"id": "PMID:176388", "title": "Naturally occurring reticuloendotheliosis in turkeys: transmission.", "content": "This report describes the natural occurrence and experimental transmission of reticuloendotheliosis in a turkey flock. In the naturally affected turkeys, lesions were present in the liver, spleen, heart, intestines, and peripheral nerves, and were composed mainly of lymphoreticular cells. The disease was experimentally reproduced in turkey poults with cellfree tissue extracts of infected birds. A type-C RNA virus similar to reticuloendotheliosis virus (strain T) was present in the tissues of turkey poults experimentally inoculated. This virus was unrelated to the type-C RNA viruses of the avian leukosis sarcoma complex.", "contents": "Naturally occurring reticuloendotheliosis in turkeys: transmission. This report describes the natural occurrence and experimental transmission of reticuloendotheliosis in a turkey flock. In the naturally affected turkeys, lesions were present in the liver, spleen, heart, intestines, and peripheral nerves, and were composed mainly of lymphoreticular cells. The disease was experimentally reproduced in turkey poults with cellfree tissue extracts of infected birds. A type-C RNA virus similar to reticuloendotheliosis virus (strain T) was present in the tissues of turkey poults experimentally inoculated. This virus was unrelated to the type-C RNA viruses of the avian leukosis sarcoma complex."} {"id": "PMID:176389", "title": "Host-range properties of murine xenotropic and ecotropic type-C viruses.", "content": "Host-range properties of xenotropic (x-tropic) and ecotropic mouse type-C viruses were determined. NB-tropic viruses replicated only in mouse and rat cells, whereas x-tropic viruses, which do not exogenously infect mouse cells, grew in cells from various other mammalian species. Great variability in susceptibilities to x-tropic viruses was demonstrated in cells from heterologous species and in cells from a single species (human). Although rat cells were susceptible to both types of viruses, hamster cells were uniformly resistant. In addition, the x-tropic viruses crossed class barriers to infect cells of avian species but not insect, fish, or reptile cells.", "contents": "Host-range properties of murine xenotropic and ecotropic type-C viruses. Host-range properties of xenotropic (x-tropic) and ecotropic mouse type-C viruses were determined. NB-tropic viruses replicated only in mouse and rat cells, whereas x-tropic viruses, which do not exogenously infect mouse cells, grew in cells from various other mammalian species. Great variability in susceptibilities to x-tropic viruses was demonstrated in cells from heterologous species and in cells from a single species (human). Although rat cells were susceptible to both types of viruses, hamster cells were uniformly resistant. In addition, the x-tropic viruses crossed class barriers to infect cells of avian species but not insect, fish, or reptile cells."} {"id": "PMID:176390", "title": "Prevention of tumor growth after intradermal injection of BCG extracts: a comparison of results in strain-2 guinea pigs from the National Institutes of Health and from the National Jewish Hospital and Research Center.", "content": "Line 10, a transplantable hepatocellular carcinoma, was obtained originally from an NIH strain-2 male guinea pig fed diethylnitrosamine. The antitumor activity of BCG and BCG extracts was evaluated in strain-2 guinea pigs obtained both from NIH and the National Jewish Hospital and Research Center (NJH). Animals were immunized with these materials and then tested for their capacity to resist the growth of intradermally injected line-10 tumor cells. Tumor growth was not prevented in 18 NIH animals immunized with living BCG. No tumor growth occurred in 1 of 22 NIH animals immunized with a residue that remained after exhaustive methanol extraction of BCG and in 1 of 44 NIH guinea pigs immunized with BCG extracts. In contrast, tumor growth was prevented in 13 of 22 similarly immunized NJH guinea pigs.", "contents": "Prevention of tumor growth after intradermal injection of BCG extracts: a comparison of results in strain-2 guinea pigs from the National Institutes of Health and from the National Jewish Hospital and Research Center. Line 10, a transplantable hepatocellular carcinoma, was obtained originally from an NIH strain-2 male guinea pig fed diethylnitrosamine. The antitumor activity of BCG and BCG extracts was evaluated in strain-2 guinea pigs obtained both from NIH and the National Jewish Hospital and Research Center (NJH). Animals were immunized with these materials and then tested for their capacity to resist the growth of intradermally injected line-10 tumor cells. Tumor growth was not prevented in 18 NIH animals immunized with living BCG. No tumor growth occurred in 1 of 22 NIH animals immunized with a residue that remained after exhaustive methanol extraction of BCG and in 1 of 44 NIH guinea pigs immunized with BCG extracts. In contrast, tumor growth was prevented in 13 of 22 similarly immunized NJH guinea pigs."} {"id": "PMID:176392", "title": "IgM antibody to a tumor-associated antigen (AG-4) induced by herpes simplex virus type 2: its use in location of the antigen in infected cells.", "content": "Rate-zonal centrifugation was used to separate 7S and 19S lg's from sera of patients with cervical cancer and of controls. The lg's were assayed for their ability to recognize AG-4, a tumor-associated antigen, and herpes simplex virus 2 (HSV-2) by various serologic assays including neutralization, immunofluorescence, and complement fixation. These studies indicated that antibody to AG-4 is a macroglobulin; antibody-fixing complement with HSV-2 is a 7S lg. The results of various serologic assays did not show absolute correlation; various tests preferentially identified some antigen-antibody reactions. We obtained evidence that AG-4 is the cytoplasm and is probably on the cell surface.", "contents": "IgM antibody to a tumor-associated antigen (AG-4) induced by herpes simplex virus type 2: its use in location of the antigen in infected cells. Rate-zonal centrifugation was used to separate 7S and 19S lg's from sera of patients with cervical cancer and of controls. The lg's were assayed for their ability to recognize AG-4, a tumor-associated antigen, and herpes simplex virus 2 (HSV-2) by various serologic assays including neutralization, immunofluorescence, and complement fixation. These studies indicated that antibody to AG-4 is a macroglobulin; antibody-fixing complement with HSV-2 is a 7S lg. The results of various serologic assays did not show absolute correlation; various tests preferentially identified some antigen-antibody reactions. We obtained evidence that AG-4 is the cytoplasm and is probably on the cell surface."} {"id": "PMID:176393", "title": "Antibody-dependent lymphocyte cytotoxicity against cells expressing Epstein-Barr virus antigens.", "content": "Antibody-dependent lymphocyte cytotoxicity (ADLC) was demonstrated against Epstein-Barr virus (EBV)-infected RAJI cells with peripheral with peripheral blood lymphocytes from EBV-infected donors. No cytotoxic activity was detected against unifected RAJl cells. The results indicated that this antibody-mediated cytotoxic reaction was directed against the same EBV-induced membrane antigens (MA) previously defined by the membrane immunofluorescence (MF) assay. Antibody to EBV-associated early antigens did not participate in this in vitro reaction. Antibody titers to EBV-induced MA were significantly higher by the ADLC assay in comparison with the MF test. A preliminary study showed no relationship between high antibody titers and the presence of EBV-associated malignancies. The possible in vivo significance of this immune reaction was discussed.", "contents": "Antibody-dependent lymphocyte cytotoxicity against cells expressing Epstein-Barr virus antigens. Antibody-dependent lymphocyte cytotoxicity (ADLC) was demonstrated against Epstein-Barr virus (EBV)-infected RAJI cells with peripheral with peripheral blood lymphocytes from EBV-infected donors. No cytotoxic activity was detected against unifected RAJl cells. The results indicated that this antibody-mediated cytotoxic reaction was directed against the same EBV-induced membrane antigens (MA) previously defined by the membrane immunofluorescence (MF) assay. Antibody to EBV-associated early antigens did not participate in this in vitro reaction. Antibody titers to EBV-induced MA were significantly higher by the ADLC assay in comparison with the MF test. A preliminary study showed no relationship between high antibody titers and the presence of EBV-associated malignancies. The possible in vivo significance of this immune reaction was discussed."} {"id": "PMID:176394", "title": "Effect of partial hepatectomy on tumor incidence and metabolism of mice fed thioacetamide.", "content": "Six-week-old male Swiss mice were given 0.03% thioacetamide (TAA) in the diet 24, 72, and 168 hours after partial hepatectomy. TAA-treated mice from all three groups were killed when they were 4, 9, and 13 months old. Intact and partially hepatectomized animals on normal diets served as controls. None of the controls evidenced neoplasms at any age. All three experimental groups developed liver tumors earlier than did intact mice treated with the TAA diet. Progressive metabolic studies on the livers or tumor tissues of treated mice showed that the levels of glucose-6-phosphatase, fructose-1,6-diphosphatase, and glycogen decreased significantly in the 4-month-old treated group when there was no significant alteration in liver histology. These parameters were lowest in the tumor tissues of treated mice.", "contents": "Effect of partial hepatectomy on tumor incidence and metabolism of mice fed thioacetamide. Six-week-old male Swiss mice were given 0.03% thioacetamide (TAA) in the diet 24, 72, and 168 hours after partial hepatectomy. TAA-treated mice from all three groups were killed when they were 4, 9, and 13 months old. Intact and partially hepatectomized animals on normal diets served as controls. None of the controls evidenced neoplasms at any age. All three experimental groups developed liver tumors earlier than did intact mice treated with the TAA diet. Progressive metabolic studies on the livers or tumor tissues of treated mice showed that the levels of glucose-6-phosphatase, fructose-1,6-diphosphatase, and glycogen decreased significantly in the 4-month-old treated group when there was no significant alteration in liver histology. These parameters were lowest in the tumor tissues of treated mice."} {"id": "PMID:176395", "title": "Mixed-culture cytopathogenicity between KC and XC oncornavirus indicator lines and \"virus-free\" human choriocarcinoma cells.", "content": "When rat (XC) cells transformed by Rous sarcoma virus and human (KC) cells were cocultivated with appropriate infected cells, cell fusion was extensive and rapid. Many human cell lines were screened, with negative results; however, several hormone-secreting human choriocarcinoma cells fused extensively with both KC and XC cells. No evidence of a virus involvement in this interaction was found by direct examination, transmission, or immunologic tests.", "contents": "Mixed-culture cytopathogenicity between KC and XC oncornavirus indicator lines and \"virus-free\" human choriocarcinoma cells. When rat (XC) cells transformed by Rous sarcoma virus and human (KC) cells were cocultivated with appropriate infected cells, cell fusion was extensive and rapid. Many human cell lines were screened, with negative results; however, several hormone-secreting human choriocarcinoma cells fused extensively with both KC and XC cells. No evidence of a virus involvement in this interaction was found by direct examination, transmission, or immunologic tests."} {"id": "PMID:176396", "title": "Vascular tumors induced by polyoma virus in pregnant rats.", "content": "Female R rats mated with an R male and inoculated in utero with polyoma virus after \"fetectomy\" developed tumors. These tumors originated in the uterus and were of fetal origin (visceral yolk sac). Histologically, they were hemangiomas or hemangiosarcomas. The latter were transplantable and grew in tissue culture. Infectious polyoma virus could not be isolated from the tumor cells kept as transplantable lines or cultured in vitro. However, the tumor cells were positive for the polyoma-specific surface antigen, polyoma tumor-specific transplantation antigen(s), and polyoma nuclear T antigen.", "contents": "Vascular tumors induced by polyoma virus in pregnant rats. Female R rats mated with an R male and inoculated in utero with polyoma virus after \"fetectomy\" developed tumors. These tumors originated in the uterus and were of fetal origin (visceral yolk sac). Histologically, they were hemangiomas or hemangiosarcomas. The latter were transplantable and grew in tissue culture. Infectious polyoma virus could not be isolated from the tumor cells kept as transplantable lines or cultured in vitro. However, the tumor cells were positive for the polyoma-specific surface antigen, polyoma tumor-specific transplantation antigen(s), and polyoma nuclear T antigen."} {"id": "PMID:176397", "title": "Prostaglandin production in cultures of BALB/3T3 and SV3T3 mouse fibroblasts.", "content": "The concentration of different prostaglandins (PG's) was determined in both cells and culture medium of growing BALB/3T3 and BALB/3T3 (3T3) cultures transformed by simian virus 40 (SV3T3). Most PG's were found in the culture medium rather than in the cells. Further, the larger PG measurements were PGE and a composite measurement of PGA and PGB. PGF was detected at lower levels. The sum of PGE and the composite measurement (PGA+PGB) was the best indication of PG production in culture. When 2-day medium collections from 3T3 and SV3T3 cells were measured by radioimmunoassay for PGs, higher concentrations of PG were detected in the media of SV3T3 cultures. This difference in PG production was not due merely to differences in cell density, since SV3T3 cells produced higher PG concentrations, even at equal cell densities. PG production for a 2-day interval was more a function of cell type than cell density.", "contents": "Prostaglandin production in cultures of BALB/3T3 and SV3T3 mouse fibroblasts. The concentration of different prostaglandins (PG's) was determined in both cells and culture medium of growing BALB/3T3 and BALB/3T3 (3T3) cultures transformed by simian virus 40 (SV3T3). Most PG's were found in the culture medium rather than in the cells. Further, the larger PG measurements were PGE and a composite measurement of PGA and PGB. PGF was detected at lower levels. The sum of PGE and the composite measurement (PGA+PGB) was the best indication of PG production in culture. When 2-day medium collections from 3T3 and SV3T3 cells were measured by radioimmunoassay for PGs, higher concentrations of PG were detected in the media of SV3T3 cultures. This difference in PG production was not due merely to differences in cell density, since SV3T3 cells produced higher PG concentrations, even at equal cell densities. PG production for a 2-day interval was more a function of cell type than cell density."} {"id": "PMID:176398", "title": "Stimulation of growth of a transplantable hepatoma in rats by parenteral nutrition.", "content": "Young BUF rats of similar ages were inoculated with the transplantable Morris hepatoma No. 7777. At 4 weeks after inoculation, 1 group was given total iv (parenteral) feeding at high caloric and nutritional levels for 2 weeks. Such total iv feeding (hyperalimentation) of rats stimulated a more rapid tumor growth in the host. In addition, the tumors from rats fed parenterally for 2 weeks had higher mitotic activity and larger areas of necrosis, which indicate that iv feeding caused the tumor to undergo faster cell turnover with greater cell production and cell loss. Analysis of organ weights showed that parenteral feeding caused atrophy of the intestines, whereas spleen weights of the hepatoma-bearing rats fed iv were greater than those of the orally fed hepatoma-bearing rats.", "contents": "Stimulation of growth of a transplantable hepatoma in rats by parenteral nutrition. Young BUF rats of similar ages were inoculated with the transplantable Morris hepatoma No. 7777. At 4 weeks after inoculation, 1 group was given total iv (parenteral) feeding at high caloric and nutritional levels for 2 weeks. Such total iv feeding (hyperalimentation) of rats stimulated a more rapid tumor growth in the host. In addition, the tumors from rats fed parenterally for 2 weeks had higher mitotic activity and larger areas of necrosis, which indicate that iv feeding caused the tumor to undergo faster cell turnover with greater cell production and cell loss. Analysis of organ weights showed that parenteral feeding caused atrophy of the intestines, whereas spleen weights of the hepatoma-bearing rats fed iv were greater than those of the orally fed hepatoma-bearing rats."} {"id": "PMID:176399", "title": "Immune reactivity in the Moloney strain of murine sarcoma virus oncogenesis: requirement of thymus-derived lymphocytes for in vivo protection.", "content": "To study the function of different lymphocyte populations in the Moloney strain of murine sarcoma virus (M-MuSV) tumorigenesis, we gave M-MuSV injections to CBA mice selectively deprived of thymus (T) lymphocytes by thymectomy, X-rradiation, and syngeneic bone marrow injection. Although no tumors appeared in the control group, 80% of the derived mice had tumors that grew progressively and ultimately killed them. In deprived mice, grafted with a syngeneic thymus (reconstituted mice) before or after an M-MuSV injection, tumors regressed or did not develop. Histologically, the lymph nodes and spleens of reconstituted mice, compared to those of deprived animals, showed repopulation of the thymus-dependent areas and prominent follicles in the cortex. Moreover, tumor tissue of reconstituted mice was extensively infiltrated by lymphocytes. To evaluate the number of lymphoid cells needed to prevent or regress M-MuSV tumors, we injected varying amounts of lymphoid cells into deprived mice. Even low lymphocyte numbers (10(6) cells) were sufficient to exert, in some cases, protection against M-MuSV tumorigenesis. This effect was not abolished by subsequent splenectomy or antilymphocyte serum treatment. Finally, deprived mice, given repeated injections of antiserum (hyperimmune) against M-MuSV, had tumors which appeared only after a prolonged latency. From these results, it is concluded that T-cell population integrity is important in affording total host protection against the M-MuSV tumors.", "contents": "Immune reactivity in the Moloney strain of murine sarcoma virus oncogenesis: requirement of thymus-derived lymphocytes for in vivo protection. To study the function of different lymphocyte populations in the Moloney strain of murine sarcoma virus (M-MuSV) tumorigenesis, we gave M-MuSV injections to CBA mice selectively deprived of thymus (T) lymphocytes by thymectomy, X-rradiation, and syngeneic bone marrow injection. Although no tumors appeared in the control group, 80% of the derived mice had tumors that grew progressively and ultimately killed them. In deprived mice, grafted with a syngeneic thymus (reconstituted mice) before or after an M-MuSV injection, tumors regressed or did not develop. Histologically, the lymph nodes and spleens of reconstituted mice, compared to those of deprived animals, showed repopulation of the thymus-dependent areas and prominent follicles in the cortex. Moreover, tumor tissue of reconstituted mice was extensively infiltrated by lymphocytes. To evaluate the number of lymphoid cells needed to prevent or regress M-MuSV tumors, we injected varying amounts of lymphoid cells into deprived mice. Even low lymphocyte numbers (10(6) cells) were sufficient to exert, in some cases, protection against M-MuSV tumorigenesis. This effect was not abolished by subsequent splenectomy or antilymphocyte serum treatment. Finally, deprived mice, given repeated injections of antiserum (hyperimmune) against M-MuSV, had tumors which appeared only after a prolonged latency. From these results, it is concluded that T-cell population integrity is important in affording total host protection against the M-MuSV tumors."} {"id": "PMID:176400", "title": "Detection of complement-dependent antibody to tumor cells in sera of strain-2 guinea pigs cured of their tumors by BCG Treatment.", "content": "Sera of strain-2 guinea pigs (cured of line-10 tumor by BCG therapy) were tested for complement-dependent, cytotoxic antibody. About 30% of the sera tested contained significant cytotoxic acitivity with the addition of human, but not syngeneic, complement. Using papain pretreated line-10 cells, we detected antibody in about 50% of the sera with syngeneic sera as the source of complement. Antibody to line-10 was also demonstrated in selected sera by indirect fluorescence and the C1 fixation and transfer test.", "contents": "Detection of complement-dependent antibody to tumor cells in sera of strain-2 guinea pigs cured of their tumors by BCG Treatment. Sera of strain-2 guinea pigs (cured of line-10 tumor by BCG therapy) were tested for complement-dependent, cytotoxic antibody. About 30% of the sera tested contained significant cytotoxic acitivity with the addition of human, but not syngeneic, complement. Using papain pretreated line-10 cells, we detected antibody in about 50% of the sera with syngeneic sera as the source of complement. Antibody to line-10 was also demonstrated in selected sera by indirect fluorescence and the C1 fixation and transfer test."} {"id": "PMID:176401", "title": "Typical type-C virus in human leukemia.", "content": "The virus HL-23, recently isolated from a patient with myelogenous leukemia, was compared by electron microscopy with virus-like particles observed in human tissues and with several mammalian type-C virus particles. It closely resembled the typical type-C virus particles of murine, feline, and nonhuman primate species, and differed from all particles previously reported in human tissues, including the atypical human placental particle.", "contents": "Typical type-C virus in human leukemia. The virus HL-23, recently isolated from a patient with myelogenous leukemia, was compared by electron microscopy with virus-like particles observed in human tissues and with several mammalian type-C virus particles. It closely resembled the typical type-C virus particles of murine, feline, and nonhuman primate species, and differed from all particles previously reported in human tissues, including the atypical human placental particle."} {"id": "PMID:176402", "title": "Lack of infectivity of bovine leukemia (C-type) virus to rats.", "content": "Sprague-Dawley rats were given ip injections of bovine culture and sheep cultures of bovine leukemia virus (BLV) and Gross passage-A leukemia virus [MuLV(G)]. Sera were tested to BLV antigens. BLV did not induce tumors in Sprague-Dawley rats, but the rats were susceptible to MuLV(G) at low doses.", "contents": "Lack of infectivity of bovine leukemia (C-type) virus to rats. Sprague-Dawley rats were given ip injections of bovine culture and sheep cultures of bovine leukemia virus (BLV) and Gross passage-A leukemia virus [MuLV(G)]. Sera were tested to BLV antigens. BLV did not induce tumors in Sprague-Dawley rats, but the rats were susceptible to MuLV(G) at low doses."} {"id": "PMID:176403", "title": "Relationship of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate to growth of dimethylbenz(a)anthracene-induced mammary tumors in rats.", "content": "Alteration of growth of dimethylbenz[a]anthracene-induced mammary tumors was caused by removal of estrogen (ovariectomy), or insulin (diabetes), or by inhibition of prolactin secretin (treatment with an ergoline derivative). The levels of cyclic AMP (cAMP) and cGMP were measured in carcinomas classified as growing, static, and regressing. The amount of cAMP, expressed as pmoles/mg tumor weight or pmoles/mg protein, was lowest in growing tumors, intermediate in static tumors, and highest in those regressing. No correlation was seen between tumor growth and cGMP levels. Cyclophosphamide-induced tumor stasis did not elevate cAMP levels. The data suggest a role of cAMP in arrest of hormone-induced tumor growth.", "contents": "Relationship of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate to growth of dimethylbenz(a)anthracene-induced mammary tumors in rats. Alteration of growth of dimethylbenz[a]anthracene-induced mammary tumors was caused by removal of estrogen (ovariectomy), or insulin (diabetes), or by inhibition of prolactin secretin (treatment with an ergoline derivative). The levels of cyclic AMP (cAMP) and cGMP were measured in carcinomas classified as growing, static, and regressing. The amount of cAMP, expressed as pmoles/mg tumor weight or pmoles/mg protein, was lowest in growing tumors, intermediate in static tumors, and highest in those regressing. No correlation was seen between tumor growth and cGMP levels. Cyclophosphamide-induced tumor stasis did not elevate cAMP levels. The data suggest a role of cAMP in arrest of hormone-induced tumor growth."} {"id": "PMID:176404", "title": "Malignant transformation of hamster brain cells in vitro by human papovavirus Bk.", "content": "Human papovavirus BK caused the malignant transformation in vitro of brain cells prepared from newborn hamsters. The transformed cells produced BK virus T antigen and grew as tumors after sc inoculation ito hamsters that developed antibodies to BK virus T antigen. The histopathology of the tumors revealed an undifferentiated glioma.", "contents": "Malignant transformation of hamster brain cells in vitro by human papovavirus Bk. Human papovavirus BK caused the malignant transformation in vitro of brain cells prepared from newborn hamsters. The transformed cells produced BK virus T antigen and grew as tumors after sc inoculation ito hamsters that developed antibodies to BK virus T antigen. The histopathology of the tumors revealed an undifferentiated glioma."} {"id": "PMID:176405", "title": "Hepatic cytologic and neoplastic changes in mice given benzidine dihydrochloride.", "content": "The administration of benzidine dihydrochloride in water to mice for up to 39 weeks resulted in hemosiderosis of the spleen, focal vacuolization of the transitional epithelium of the urinary bladder, and chronic inflammation and cytologic and neoplastic changes in the liver. Basophilic and acidophilic cytologic foci appeared in the liver as two distinct entities and both appeared preneoplastic. Benign and malignant liver tumors were also seen. Both types of cytologic changes and malignant liver tumors were more common in the female than male mouse.", "contents": "Hepatic cytologic and neoplastic changes in mice given benzidine dihydrochloride. The administration of benzidine dihydrochloride in water to mice for up to 39 weeks resulted in hemosiderosis of the spleen, focal vacuolization of the transitional epithelium of the urinary bladder, and chronic inflammation and cytologic and neoplastic changes in the liver. Basophilic and acidophilic cytologic foci appeared in the liver as two distinct entities and both appeared preneoplastic. Benign and malignant liver tumors were also seen. Both types of cytologic changes and malignant liver tumors were more common in the female than male mouse."} {"id": "PMID:176407", "title": "Epstein-Barr virus in an American patient with Burkitt's lymphoma: detection of viral genome in tumor tissue and establishment of a tumor-derived cell line (NAB).", "content": "Epstein-Barr virus (EBV) DNA (17.7 genome equivalents/cell) was found in tumor tissue from an American patient with Burkitt's lymphoma who had never traveled outside the United States. A lymphoid cell line (NAB) containing the EBV genome was established from tumor tissue from this patient; characteristics of this cell line were described. Previous Burkitt's tumors found in Americans and examined by molecular hybridization were negative for EBV DNA. Our results suggested that EBV is associated with at least some American Burkitt's tumors.", "contents": "Epstein-Barr virus in an American patient with Burkitt's lymphoma: detection of viral genome in tumor tissue and establishment of a tumor-derived cell line (NAB). Epstein-Barr virus (EBV) DNA (17.7 genome equivalents/cell) was found in tumor tissue from an American patient with Burkitt's lymphoma who had never traveled outside the United States. A lymphoid cell line (NAB) containing the EBV genome was established from tumor tissue from this patient; characteristics of this cell line were described. Previous Burkitt's tumors found in Americans and examined by molecular hybridization were negative for EBV DNA. Our results suggested that EBV is associated with at least some American Burkitt's tumors."} {"id": "PMID:176408", "title": "Lymphoproliferative diseases of fowl: chromosome breaks caused in lymphocytes by JM-V herpesvirus.", "content": "Chromosome preparations were made of bone marrow cells and peripheral lymphocytes isolated from chicks that developed leukemia following infection with JM-V herpes-virus. Karyotypic analysis revealed a high frequency of chromosome breaks and aneuploidy, as well as some pulverization of chromosomes. The number of chromosome breaks began to increase at 2-3 days post infection, and by 5 days post infection it reached 12.7% of bone marrow cells and 17.2% of peripheral lymphocytes. Similarly, the number of aneuploid metaphase figures increased rapidly and reached 12% of bone marrow cells and 19% of peripheral lymphocytes at 5 days post infection. Some specificity was observed in the chromosomes that were affected.", "contents": "Lymphoproliferative diseases of fowl: chromosome breaks caused in lymphocytes by JM-V herpesvirus. Chromosome preparations were made of bone marrow cells and peripheral lymphocytes isolated from chicks that developed leukemia following infection with JM-V herpes-virus. Karyotypic analysis revealed a high frequency of chromosome breaks and aneuploidy, as well as some pulverization of chromosomes. The number of chromosome breaks began to increase at 2-3 days post infection, and by 5 days post infection it reached 12.7% of bone marrow cells and 17.2% of peripheral lymphocytes. Similarly, the number of aneuploid metaphase figures increased rapidly and reached 12% of bone marrow cells and 19% of peripheral lymphocytes at 5 days post infection. Some specificity was observed in the chromosomes that were affected."} {"id": "PMID:176409", "title": "Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine.", "content": "Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year. The animals were then observed for an additional 12 months for the induction of neoplasms. Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized. In the 60 monocrotaline-treated rats, 31 widely dispersed tumors of various cell types were recorded. The reason suggested for the variation in tissue response was that the metabolite dehydroretronecine is a proximate carcinogen, whereas monocrotaline must first be metabolized before its carcinogenic potential is realized.", "contents": "Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine. Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year. The animals were then observed for an additional 12 months for the induction of neoplasms. Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized. In the 60 monocrotaline-treated rats, 31 widely dispersed tumors of various cell types were recorded. The reason suggested for the variation in tissue response was that the metabolite dehydroretronecine is a proximate carcinogen, whereas monocrotaline must first be metabolized before its carcinogenic potential is realized."} {"id": "PMID:176410", "title": "Effect of phosphonoacetate on Marek's disease virus replication.", "content": "Phosphonoacetate (PA), but not any of its analogues tested, effectively inhibited avian herpesvirus replication and viral DNA synthesis in cell cultures. At 100 mug/ml culture medium, PA completely inhibited the replication of Marek's disease virus (MDV), herpesvirus of turkeys, and owl herpesvirus, but had no measurable effect on normal cell growth. PA also inhibited DNA polymerases induced by these avian viruses. Enzyme inhibition was 50% at a PA concentration of 0.2 mug/ml. At a concentration of 3-6 mug/ml, the compound also effected a 50% inhibition of alpha (maxi) enzyme of the host DNA polymerase. It had no effect on the host beta (mini) enzyme. When administered to chickens, PA did not inhibit the replication of MDV, nor did it prevent the development of lymphoma.", "contents": "Effect of phosphonoacetate on Marek's disease virus replication. Phosphonoacetate (PA), but not any of its analogues tested, effectively inhibited avian herpesvirus replication and viral DNA synthesis in cell cultures. At 100 mug/ml culture medium, PA completely inhibited the replication of Marek's disease virus (MDV), herpesvirus of turkeys, and owl herpesvirus, but had no measurable effect on normal cell growth. PA also inhibited DNA polymerases induced by these avian viruses. Enzyme inhibition was 50% at a PA concentration of 0.2 mug/ml. At a concentration of 3-6 mug/ml, the compound also effected a 50% inhibition of alpha (maxi) enzyme of the host DNA polymerase. It had no effect on the host beta (mini) enzyme. When administered to chickens, PA did not inhibit the replication of MDV, nor did it prevent the development of lymphoma."} {"id": "PMID:176411", "title": "Regression of established tumors and induction of tumor immunity by intratumor chemotherapy.", "content": "The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells.", "contents": "Regression of established tumors and induction of tumor immunity by intratumor chemotherapy. The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells."} {"id": "PMID:176412", "title": "Epithelial cell cultures from normal and cancerous human tissues.", "content": "Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal.", "contents": "Epithelial cell cultures from normal and cancerous human tissues. Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal."} {"id": "PMID:176413", "title": "Virus-like particles in geometric tubuloreticular structures.", "content": "Tubuloreticular structures of the geometric type were observed in dog osteosarcoma cells (D17a) before and after cocultivation with human placenta cells and before and after passage of the cocultivated cells through NIH nude mice. After passage through NIH nude mice, the reestablished cultures regularly produced conventional murine type-C particles and displayed budding virus-like particles (VLP) within the tubuloreticular structures. VLP, tentatively considered an aberrant form of type-C particles, were presumably of murine origin since they were not observed in the osteosarcoma cells before passage through NIH nude mice.", "contents": "Virus-like particles in geometric tubuloreticular structures. Tubuloreticular structures of the geometric type were observed in dog osteosarcoma cells (D17a) before and after cocultivation with human placenta cells and before and after passage of the cocultivated cells through NIH nude mice. After passage through NIH nude mice, the reestablished cultures regularly produced conventional murine type-C particles and displayed budding virus-like particles (VLP) within the tubuloreticular structures. VLP, tentatively considered an aberrant form of type-C particles, were presumably of murine origin since they were not observed in the osteosarcoma cells before passage through NIH nude mice."} {"id": "PMID:176414", "title": "Humoral immune responses of cats to feline leukemia virus: comparison of responses to the major structural protein p30 and to a virus-specific cell membrane antigen (FOCMA).", "content": "Radioimmunoprecipitation was used to test cat sera for ability to bind to the purified major internal protein p30 of feline leukemia viurs (FeLV), to the endogenous cat virus (RD-114), and to murine leukemia virus (MuLV). The data were compared with results of tests for antibody to the feline oncornavirus-associated cell membrane antigen FOCMA and for the presence of viremia. In contrast to the general lack of free antibody to FeLV p30 in a random sample of healthy cats, high levels of antibody to FeLV p30 and FOCMA were found in normal animals from high-leukemia-cluster households. Titers of greater than or equal to 200 for p30 and greater than or equal to 32 for FOCMA were found in nonviremic animals; a percentage of animals with high FOCMA titers and lower or no p30 binding activity were viremic. Animals with neoplasms were low or negative for FOCMA antibody and did not have high titers of free p30 antibody. The p30 binding activity could be divided into three main categories: high binding with FeLV p30 and much lower activity with RD-114 and MuLV p30's, as seen with hyperimmune sera; high binding with FeLV and RD-114 p30's and low activity with MuLV p30, possibly indicative of specific antibody to both of the aforementioned proteins; and low level binding to all three p30's.", "contents": "Humoral immune responses of cats to feline leukemia virus: comparison of responses to the major structural protein p30 and to a virus-specific cell membrane antigen (FOCMA). Radioimmunoprecipitation was used to test cat sera for ability to bind to the purified major internal protein p30 of feline leukemia viurs (FeLV), to the endogenous cat virus (RD-114), and to murine leukemia virus (MuLV). The data were compared with results of tests for antibody to the feline oncornavirus-associated cell membrane antigen FOCMA and for the presence of viremia. In contrast to the general lack of free antibody to FeLV p30 in a random sample of healthy cats, high levels of antibody to FeLV p30 and FOCMA were found in normal animals from high-leukemia-cluster households. Titers of greater than or equal to 200 for p30 and greater than or equal to 32 for FOCMA were found in nonviremic animals; a percentage of animals with high FOCMA titers and lower or no p30 binding activity were viremic. Animals with neoplasms were low or negative for FOCMA antibody and did not have high titers of free p30 antibody. The p30 binding activity could be divided into three main categories: high binding with FeLV p30 and much lower activity with RD-114 and MuLV p30's, as seen with hyperimmune sera; high binding with FeLV and RD-114 p30's and low activity with MuLV p30, possibly indicative of specific antibody to both of the aforementioned proteins; and low level binding to all three p30's."} {"id": "PMID:176415", "title": "Hamster ependymomas produced by intracerebral inoculation of a human papovavirus (MMV).", "content": "Ependymomas were produced in 3 of 11 newborn hamsters inoculated intracerebrally with a human papovavirus (MMV) isolated from a malignant lymphoma of the brain of a child with Wiskott-Aldrich syndrome. One of the tumors was serially transplanted into weanling hamsters. Cells from the transplanted tumors and from cell cultures derived from these tumors contained an intranuclear \"T\" antigen that reacted with simian virus 40 T antibody.", "contents": "Hamster ependymomas produced by intracerebral inoculation of a human papovavirus (MMV). Ependymomas were produced in 3 of 11 newborn hamsters inoculated intracerebrally with a human papovavirus (MMV) isolated from a malignant lymphoma of the brain of a child with Wiskott-Aldrich syndrome. One of the tumors was serially transplanted into weanling hamsters. Cells from the transplanted tumors and from cell cultures derived from these tumors contained an intranuclear \"T\" antigen that reacted with simian virus 40 T antibody."} {"id": "PMID:176419", "title": "Rat sequences of the Kirsten and Harvey murine sarcoma virus genomes: nature, origin, and expression in rat tumor RNA.", "content": "Two murine sarcoma viruses, the Kirsten and the Harvey, were isolated by passage of mouse type C leukemia viruses through rats. These sarcoma viruses have genomes containing portions of their parental type C mouse leukemia virus genomes, in stable association with specific rat cellular sequences that we find to be quite likely not those of a rat type C leukemia virus. To determine if these murine sarcoma viruses provide a model relevant to the events occurring in spontaneous tumors, we have hybridized DNA and RNA prepared from rat tumors and normal rat tissues to [3H]DNA prepared from the Kirsten murine sarcoma virus. We have also hybridized these rat tissue nucleic acids to [3H]DNA prepared from a respresentative endogenous rat type C leukemia virus, the WFU (Wistar-Furth). Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected in the DNA of both tumor and normal tissues, with no evidence of either gene amplification or additional sequences being present in tumor DNA. Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected at elevated concentrations in the RNA of many rat tumors and in specific groups of normal tissues.", "contents": "Rat sequences of the Kirsten and Harvey murine sarcoma virus genomes: nature, origin, and expression in rat tumor RNA. Two murine sarcoma viruses, the Kirsten and the Harvey, were isolated by passage of mouse type C leukemia viruses through rats. These sarcoma viruses have genomes containing portions of their parental type C mouse leukemia virus genomes, in stable association with specific rat cellular sequences that we find to be quite likely not those of a rat type C leukemia virus. To determine if these murine sarcoma viruses provide a model relevant to the events occurring in spontaneous tumors, we have hybridized DNA and RNA prepared from rat tumors and normal rat tissues to [3H]DNA prepared from the Kirsten murine sarcoma virus. We have also hybridized these rat tissue nucleic acids to [3H]DNA prepared from a respresentative endogenous rat type C leukemia virus, the WFU (Wistar-Furth). Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected in the DNA of both tumor and normal tissues, with no evidence of either gene amplification or additional sequences being present in tumor DNA. Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected at elevated concentrations in the RNA of many rat tumors and in specific groups of normal tissues."} {"id": "PMID:176420", "title": "Endonucleases and simian virus 40 virions: origin of a virion-associated endonuclease.", "content": "The origin and role of the endonuclease activity associated with purified virions of simian virus 40, previously described by this and other laboratories, have been further investigated. We found that the enzymatic activity from virions of temperature-sensitive (ts) mutants is not more heat labile than that from wild-type virions. This result was obtained for a variety of ts mutants, including three of the tsA class, and in experiments in which the enzyme was tested in both the presence and absence of viral particles. Comparison of the viron enzyme with endonucleases prepared from either serum or nuclei of uninfected cells reveals a similarity between the viron and serum enzymes based on chromatographic behavior and relative activity with different cations. Virus particles prepared free of this endonuclease were still infectious. We were unsuccessful in uncovering endonuclease in such preparations upon disruption. These data emphasize the necessity for caution in interpreting the role of particle-associated enzymes.", "contents": "Endonucleases and simian virus 40 virions: origin of a virion-associated endonuclease. The origin and role of the endonuclease activity associated with purified virions of simian virus 40, previously described by this and other laboratories, have been further investigated. We found that the enzymatic activity from virions of temperature-sensitive (ts) mutants is not more heat labile than that from wild-type virions. This result was obtained for a variety of ts mutants, including three of the tsA class, and in experiments in which the enzyme was tested in both the presence and absence of viral particles. Comparison of the viron enzyme with endonucleases prepared from either serum or nuclei of uninfected cells reveals a similarity between the viron and serum enzymes based on chromatographic behavior and relative activity with different cations. Virus particles prepared free of this endonuclease were still infectious. We were unsuccessful in uncovering endonuclease in such preparations upon disruption. These data emphasize the necessity for caution in interpreting the role of particle-associated enzymes."} {"id": "PMID:176421", "title": "Rate of virus-specific RNA synthesis in synchronized chicken embryo fibroblasts infected with avian leukosis virus.", "content": "The rate of avian leukosis virus (ALV)-specific RNA synthesis has been examined in bot- uninfected and ALV-infected synchronized chicken embryo fibroblasts. RNA from cells labeled for 2h with [3H]uridine was hybridized with avian myeloblastosis virus poly(dC)-DNA, and the hybridized RNA was analyzed with poly(I)-spephadex chromatography. Approximately 0.5% of the RNA synthesized in ALV-infected cells was detected as virus specific, and no more than a twofold variation in the rate of synthesis was detected at different times in the cell cycle. In synchronized uninfected chicken embryo fibroblasts, approximately 0.03% of the RNA synthesized was detected as virus specific, and no significant variation in the rate of synthesis was observed during the cell cycle. Treatment of ALV-infected chicken embryo fibroblasts with cytosine arabinoside or colchicine was used to block cells at different stages in the cell cycle. The rates of virus-specific RNA synthesis in cells so treated did not differ significantly from the rates in either stationary or unsynchronized virus-infected chicken embryo fibroblasts. These findings support the conclusion that after the initial division of an ALV-infected chicken embryo fibroblast and the initiation of virus RNA synthesis, the rate of virus-specific RNA synthesis is independent of the cell cycle.", "contents": "Rate of virus-specific RNA synthesis in synchronized chicken embryo fibroblasts infected with avian leukosis virus. The rate of avian leukosis virus (ALV)-specific RNA synthesis has been examined in bot- uninfected and ALV-infected synchronized chicken embryo fibroblasts. RNA from cells labeled for 2h with [3H]uridine was hybridized with avian myeloblastosis virus poly(dC)-DNA, and the hybridized RNA was analyzed with poly(I)-spephadex chromatography. Approximately 0.5% of the RNA synthesized in ALV-infected cells was detected as virus specific, and no more than a twofold variation in the rate of synthesis was detected at different times in the cell cycle. In synchronized uninfected chicken embryo fibroblasts, approximately 0.03% of the RNA synthesized was detected as virus specific, and no significant variation in the rate of synthesis was observed during the cell cycle. Treatment of ALV-infected chicken embryo fibroblasts with cytosine arabinoside or colchicine was used to block cells at different stages in the cell cycle. The rates of virus-specific RNA synthesis in cells so treated did not differ significantly from the rates in either stationary or unsynchronized virus-infected chicken embryo fibroblasts. These findings support the conclusion that after the initial division of an ALV-infected chicken embryo fibroblast and the initiation of virus RNA synthesis, the rate of virus-specific RNA synthesis is independent of the cell cycle."} {"id": "PMID:176422", "title": "DNA synthesis in polyoma virus infection. IV. Mechanism of formation of closed-circular viral DNA deficient in superhelical turns.", "content": "A marked reduction in the rate of viral DNA synthesis is accompanied by an alteration to the superhelicity of progeny DNA in polyoma virus-infected cells in which protein synthesis has been inhibited by cycloheximide. Viral DNA molecules formed in the presence of cycloheximide consist predominantly of closed-circular monometric species (referred to as form Ic) characterized by a decreased superhelix density, corresponding to deltasigmao = 0.0195, as compared to form I DNA by propidium diiodide-cesium chloride isopycnic analysis. Form Ic is synthesized on pre-existing form I templates without the intervention of progeny form I as an intermediate. It is concluded that inhibition of protein synthesis results in the alteration of some process in the closure of daughter DNA that leads to a marked reduction of superhelical turns of progeny molecules. About two-thirds of form Ic molecules return to the form I conformation upon reversal of cycloheximide inhibition by a mechanism independent of DNA replication.", "contents": "DNA synthesis in polyoma virus infection. IV. Mechanism of formation of closed-circular viral DNA deficient in superhelical turns. A marked reduction in the rate of viral DNA synthesis is accompanied by an alteration to the superhelicity of progeny DNA in polyoma virus-infected cells in which protein synthesis has been inhibited by cycloheximide. Viral DNA molecules formed in the presence of cycloheximide consist predominantly of closed-circular monometric species (referred to as form Ic) characterized by a decreased superhelix density, corresponding to deltasigmao = 0.0195, as compared to form I DNA by propidium diiodide-cesium chloride isopycnic analysis. Form Ic is synthesized on pre-existing form I templates without the intervention of progeny form I as an intermediate. It is concluded that inhibition of protein synthesis results in the alteration of some process in the closure of daughter DNA that leads to a marked reduction of superhelical turns of progeny molecules. About two-thirds of form Ic molecules return to the form I conformation upon reversal of cycloheximide inhibition by a mechanism independent of DNA replication."} {"id": "PMID:176423", "title": "DNA synthesis in polyoma virus infection. V. Kinetic evidence for two requirements for protein synthesis during viral DNA replication.", "content": "Protein synthesis in polyoma virus-infected cells was inhibited by 99% within 4 min after exposure to 10 mug of cycloheximide per ml. Subsequent to the block in protein synthesis, the rate of viral DNA synthesis declined via inhibition of the rate of initiation of new rounds of genome replication (Yu and Cheevers, 1976). This process was inhibited with complex kinetics: within 15 min after the addition of cycloheximide, the rate of formation of closed-circular viral DNA was reduced by about one-half. Thereafter, DNA synthesis in cycloheximide-treated cells declined more slowly, reaching a level of 10% of untreated cells only after approximately 2 h. Protein synthesis was also required for normal closure of progeny form I DNA: in the presence of cycloheximide, DNA synthesis was diverted from the production of form I to form Ic, a monomeric closed-circular DNA component deficient in superhelical turns (Yu and Cheevers, 1976). Form I is replaced by Ic with first-order exponential kinetics. It is concluded that at least two proteins are involved in the control of polyoma DNA replication. One is apparently a stoichiometric requirement involved in the initiation step of viral DNA synthesis, since this process cannot be maintained at a normal rate for more than a few minutes in the absence of protein synthesis. The second protein requirement, governing the closure of newly synthesized progeny DNA, is considered distinct from the \"initiation\" protein on the basis of the kinetic data.", "contents": "DNA synthesis in polyoma virus infection. V. Kinetic evidence for two requirements for protein synthesis during viral DNA replication. Protein synthesis in polyoma virus-infected cells was inhibited by 99% within 4 min after exposure to 10 mug of cycloheximide per ml. Subsequent to the block in protein synthesis, the rate of viral DNA synthesis declined via inhibition of the rate of initiation of new rounds of genome replication (Yu and Cheevers, 1976). This process was inhibited with complex kinetics: within 15 min after the addition of cycloheximide, the rate of formation of closed-circular viral DNA was reduced by about one-half. Thereafter, DNA synthesis in cycloheximide-treated cells declined more slowly, reaching a level of 10% of untreated cells only after approximately 2 h. Protein synthesis was also required for normal closure of progeny form I DNA: in the presence of cycloheximide, DNA synthesis was diverted from the production of form I to form Ic, a monomeric closed-circular DNA component deficient in superhelical turns (Yu and Cheevers, 1976). Form I is replaced by Ic with first-order exponential kinetics. It is concluded that at least two proteins are involved in the control of polyoma DNA replication. One is apparently a stoichiometric requirement involved in the initiation step of viral DNA synthesis, since this process cannot be maintained at a normal rate for more than a few minutes in the absence of protein synthesis. The second protein requirement, governing the closure of newly synthesized progeny DNA, is considered distinct from the \"initiation\" protein on the basis of the kinetic data."} {"id": "PMID:176424", "title": "Lack of infectivity of the endogenous avian leukosis virus-related genes in the DNA of uninfected chicken cells.", "content": "The infectivity of the avian leukosis virus-related genes in the DNA of four genetically distinct types of chicken cells was determined. Infectious DNA of Rous-associated virus-O(RAV-O) was obtained from V- chicken cells which were experimentally infected with RAV-O and from V+tvbs chicken cells, which spontaneously produced RAV-O and were sensitive to exogenous RAV-O infection. However, infectious DNA of RAV-O was not obtained from uninfected V- chicken cells or from V+tvbr chicken cells, which spontaneously produced a low titer of RAV-O but were resistant to exogenous RAV-O infection. No detectable amplification of the RAV-O related DNA sequences in the V+tvbs cells was found by hybridization of RAV-O 125I-labeled RNA to the DNAs of V+tvbs and uninfected V- cells. These results indicate that the endogenous avian leukosis virus-related genes in uninfected V- and V+tvbr cells differ from the RAV-O proviruses in RAV-O-infected V- and V+tvbs cells. The lack of infectivity of the DNA of V+tvbr cells is consistent with the hypothesis that the endogenous RAV-O genome in V+tvbr cells is linked to a cis-acting control element, which results in its inefficient expression.", "contents": "Lack of infectivity of the endogenous avian leukosis virus-related genes in the DNA of uninfected chicken cells. The infectivity of the avian leukosis virus-related genes in the DNA of four genetically distinct types of chicken cells was determined. Infectious DNA of Rous-associated virus-O(RAV-O) was obtained from V- chicken cells which were experimentally infected with RAV-O and from V+tvbs chicken cells, which spontaneously produced RAV-O and were sensitive to exogenous RAV-O infection. However, infectious DNA of RAV-O was not obtained from uninfected V- chicken cells or from V+tvbr chicken cells, which spontaneously produced a low titer of RAV-O but were resistant to exogenous RAV-O infection. No detectable amplification of the RAV-O related DNA sequences in the V+tvbs cells was found by hybridization of RAV-O 125I-labeled RNA to the DNAs of V+tvbs and uninfected V- cells. These results indicate that the endogenous avian leukosis virus-related genes in uninfected V- and V+tvbr cells differ from the RAV-O proviruses in RAV-O-infected V- and V+tvbs cells. The lack of infectivity of the DNA of V+tvbr cells is consistent with the hypothesis that the endogenous RAV-O genome in V+tvbr cells is linked to a cis-acting control element, which results in its inefficient expression."} {"id": "PMID:176425", "title": "Effect of medium of lowered NaCl concentration on virus release and protein synthesis in cells infected with reticuloendotheliosis virus.", "content": "When cultures producing reticuloendotheliosis virus were incubated for 24 h in medium of lowered NaCl concentration, virus production was inhibited. The extent of inhibition increased as the salt concentration of the medium was decreased. The inhibition was rapidly reversed by replacement of low-salt medium with normal medium. During the first hour after the inhibited cultures were returned to normal medium, virus was released at an accelerated rate, making the total amount of virus released by inhibited and control cultures the same. After 1 h in normal medium, the rate of virus production in the previously inhibited cultures was the same as in the control cultures. Incubation of infected cells in low-salt medium resulted in a 60% decrease in the overall rate of protein synthesis. Although returning the cells to normal medium rapidly reversed the inhibition of virus production, it did not rapidly increase the rate of protein synthesis. These results suggest that host cell-directed protein synthesis is preferentially inhibited by the low-ionic-strength medium, whereas that required for virus production continues.", "contents": "Effect of medium of lowered NaCl concentration on virus release and protein synthesis in cells infected with reticuloendotheliosis virus. When cultures producing reticuloendotheliosis virus were incubated for 24 h in medium of lowered NaCl concentration, virus production was inhibited. The extent of inhibition increased as the salt concentration of the medium was decreased. The inhibition was rapidly reversed by replacement of low-salt medium with normal medium. During the first hour after the inhibited cultures were returned to normal medium, virus was released at an accelerated rate, making the total amount of virus released by inhibited and control cultures the same. After 1 h in normal medium, the rate of virus production in the previously inhibited cultures was the same as in the control cultures. Incubation of infected cells in low-salt medium resulted in a 60% decrease in the overall rate of protein synthesis. Although returning the cells to normal medium rapidly reversed the inhibition of virus production, it did not rapidly increase the rate of protein synthesis. These results suggest that host cell-directed protein synthesis is preferentially inhibited by the low-ionic-strength medium, whereas that required for virus production continues."} {"id": "PMID:176426", "title": "Characterization and translation of methylated and unmethylated vesicular stomatitis virus mRNA synthesized in vitro by ribonucleoprotein particles from vesicular stomatitis virus-infected L cells.", "content": "Ribonucleoprotein particles isolated from extracts of vesicular stomatitis virus (VSV) -infected L cells synthesized in vitro four classes of polyadenylated RNA sedimenting at 29S, 19S, 17S, and 13S. When synthesized in vitro in the presence of the methyl donor S-adenosyl methionine, these RNA species contained the following 5'-terminal structures: (i) m7G5ppp5'AmpAp(70%) ; (ii) m7G5'ppp5'AmpAmpNp (20%) and (iii) pppAp (10%). In the presence of the methylation inhibitor S-adenosylhomocysteine, however, the mRNA contained the 5'-terminal structures G5'ppp5'Ap (80%) and pppAp (20%). The mRNA's synthesized in vitro were translated in the homologous ascites and the heterologous wheat embryo cell-free systems. In both, the products were shown by sodium dodecyl sulfate gel electrophoresis and by immunoprecipitation to contain all five viral proteins, L, G, N, NS, and M. The presumed precursor to the G protein (G*) was also identified by fingerprint analysis. Methylated VSV mRNA was more active in protein synthesis than unmethylated mRNA in both the ascites system and the wheat embryo systems. Addition of S-adenosylmethionine stimulated translation of unmethylated mRNA in the wheat embryo but not in the ascites extract. S-adenosylhomocysteine, however, by preventing mRNA methylation inhibited the translation of unmethylated VSV mRNA in both systems. The mRNA methylating activity present in wheat embryo S-30 extracts was recovered in the ribosome-free supernatant fraction (S-150) and was insensitive to the protein synthesis inhibitor pactamycin.", "contents": "Characterization and translation of methylated and unmethylated vesicular stomatitis virus mRNA synthesized in vitro by ribonucleoprotein particles from vesicular stomatitis virus-infected L cells. Ribonucleoprotein particles isolated from extracts of vesicular stomatitis virus (VSV) -infected L cells synthesized in vitro four classes of polyadenylated RNA sedimenting at 29S, 19S, 17S, and 13S. When synthesized in vitro in the presence of the methyl donor S-adenosyl methionine, these RNA species contained the following 5'-terminal structures: (i) m7G5ppp5'AmpAp(70%) ; (ii) m7G5'ppp5'AmpAmpNp (20%) and (iii) pppAp (10%). In the presence of the methylation inhibitor S-adenosylhomocysteine, however, the mRNA contained the 5'-terminal structures G5'ppp5'Ap (80%) and pppAp (20%). The mRNA's synthesized in vitro were translated in the homologous ascites and the heterologous wheat embryo cell-free systems. In both, the products were shown by sodium dodecyl sulfate gel electrophoresis and by immunoprecipitation to contain all five viral proteins, L, G, N, NS, and M. The presumed precursor to the G protein (G*) was also identified by fingerprint analysis. Methylated VSV mRNA was more active in protein synthesis than unmethylated mRNA in both the ascites system and the wheat embryo systems. Addition of S-adenosylmethionine stimulated translation of unmethylated mRNA in the wheat embryo but not in the ascites extract. S-adenosylhomocysteine, however, by preventing mRNA methylation inhibited the translation of unmethylated VSV mRNA in both systems. The mRNA methylating activity present in wheat embryo S-30 extracts was recovered in the ribosome-free supernatant fraction (S-150) and was insensitive to the protein synthesis inhibitor pactamycin."} {"id": "PMID:176427", "title": "Anatomy of herpes simplex virus DNA. V. Terminally repetitive sequences.", "content": "Native DNA from four strains of herpes simplex virus 1 (HSV-1) circularized after digestion with the lambda exonuclease, indicating that the molecules were terminally repetitious. In two strains, the terminal repetition was evident in nearly 50% of the DNA molecules. Maximal circularization was observed when only 0.25 to 0.5% of the DNA was depolymerized by the exonuclease, suggesting that the minimal size of the terminally repetitious regions is in the range of 400 to 800 bases pairs. More extensive exonuclease treatment resulted in a reduction in the frequency of circularization. To determine whether the terminally repetitive regions themselves contained self-annealing sequences that were precluding circularization of more extensively digested DNA, the terminal fragments from HinIII restriction endonuclease digests were isolated, denatured, and tested for their ability to self-anneal. The results of hydroxyapatite column chromatography and electron microscope examination of the terminal regions are consistent with this hypothesis.", "contents": "Anatomy of herpes simplex virus DNA. V. Terminally repetitive sequences. Native DNA from four strains of herpes simplex virus 1 (HSV-1) circularized after digestion with the lambda exonuclease, indicating that the molecules were terminally repetitious. In two strains, the terminal repetition was evident in nearly 50% of the DNA molecules. Maximal circularization was observed when only 0.25 to 0.5% of the DNA was depolymerized by the exonuclease, suggesting that the minimal size of the terminally repetitious regions is in the range of 400 to 800 bases pairs. More extensive exonuclease treatment resulted in a reduction in the frequency of circularization. To determine whether the terminally repetitive regions themselves contained self-annealing sequences that were precluding circularization of more extensively digested DNA, the terminal fragments from HinIII restriction endonuclease digests were isolated, denatured, and tested for their ability to self-anneal. The results of hydroxyapatite column chromatography and electron microscope examination of the terminal regions are consistent with this hypothesis."} {"id": "PMID:176428", "title": "Persistent reovirus infection of CHO cells resulting in virus resistance.", "content": "We obtained a persistently infected line of Chinese hamster ovary cells by selection for resistance to reovirus infection. The cells were persistently infected by a population of viruses that were (i) cytopathic for parental chinese hamster ovary cells and (ii) similar to wild-type reovirus in molecular characteristics. The growth rate, plating efficiency, and morphology of the cells were altered. A large majority of the cells in the population were infected. There was no detectable interferon present in the medium. The cells were relatively resistant to a wide range of viruses.", "contents": "Persistent reovirus infection of CHO cells resulting in virus resistance. We obtained a persistently infected line of Chinese hamster ovary cells by selection for resistance to reovirus infection. The cells were persistently infected by a population of viruses that were (i) cytopathic for parental chinese hamster ovary cells and (ii) similar to wild-type reovirus in molecular characteristics. The growth rate, plating efficiency, and morphology of the cells were altered. A large majority of the cells in the population were infected. There was no detectable interferon present in the medium. The cells were relatively resistant to a wide range of viruses."} {"id": "PMID:176429", "title": "Genomic complexities of murine leukemia and sarcoma, reticuloendotheliosis, and visna viruses.", "content": "The genetic complexities of several ribodeoxyviruses were measured by quantitative analysis of unique RNase T1-resistant oligonucleotides from 60-70S viral RNAs. Moloney murine leukemia virus was found to have an RNA complexity of 3.5 x 10(6) daltons, whereas Moloney murine sarcoma virus had a significantly smaller genome size of 2.3 x 10(6). Reticuleondotheliosis and visna virus RNAs had complexities of 3.9 x 10(6), respectively. Analysis of RNase A-resistant oligonucleotides of Rous sarcoma virus RNA gave a complexity of 3.6 x 10(6), similar to that previously obtained with RNase T1-resistant oligonucleotides. Since each of these viruses was found to have a unique sequence genomic complexity near the molecular weight of a single 30-40S viral RNA subunit, it was concluded that ribodeoxyvirus genomes are at least largely polyploid.", "contents": "Genomic complexities of murine leukemia and sarcoma, reticuloendotheliosis, and visna viruses. The genetic complexities of several ribodeoxyviruses were measured by quantitative analysis of unique RNase T1-resistant oligonucleotides from 60-70S viral RNAs. Moloney murine leukemia virus was found to have an RNA complexity of 3.5 x 10(6) daltons, whereas Moloney murine sarcoma virus had a significantly smaller genome size of 2.3 x 10(6). Reticuleondotheliosis and visna virus RNAs had complexities of 3.9 x 10(6), respectively. Analysis of RNase A-resistant oligonucleotides of Rous sarcoma virus RNA gave a complexity of 3.6 x 10(6), similar to that previously obtained with RNase T1-resistant oligonucleotides. Since each of these viruses was found to have a unique sequence genomic complexity near the molecular weight of a single 30-40S viral RNA subunit, it was concluded that ribodeoxyvirus genomes are at least largely polyploid."} {"id": "PMID:176430", "title": "Level of specific prereplicative mRNA's during bacteriophage T4 regA-, 43- and T4 43- infection of Escherichia coli B.", "content": "The role of the T4 bacteriophage regA gene in stabilizing early mRNA was investigated by assaying the level of functional mRNA from eight prereplicative genes (56 [dCMP hydroxymethylase], cd [dCMP deaminase], 1 [deoxynucleotide kinase], rIIA, rIIB, 46 [DNA arrest], and 45) during extended infection of Escherichia coli B with T4 regA-, 43- and T4 43- bacteriophage. The above gene-specific transcripts in RNA isolated from infected cells were quantitated by translation with an E. coli B cell-free system. Conditions were chosen to insure that the amount of gene product formed in vitro, measured either as an enzyme activity or as a radioactive band in acrylamide gel, was directly proportional to the level of mRNA present. The failure of T4 regA-, 43- phage to terminate prereplicative synthesis (Wiberg et al., 1973) resulted in an enhanced production of many early gene products over those formed during T4 43- infection. This increase did not appear to be associated with an increment in mRNA levels, since in the present study gene-specific early mRNA's were found to be only marginally elevated and slightly more stable in T4 regA-, 43-- than in T4 43--infected cells. Of interest was the observation that significant quantities of all of the mRNA's studied; with the exception of those from genes 45 and 46, could be isolated from T4 43--infected cells after synthesis of the respective gene products had ceased. On termination of normal prereplicative synthesis during infection with T4 43- phage, polyribosomes were found to be dissociated completely, a finding which suggests that the residual mRNA present in these cells is free in the cytoplasm. The persistence in T4 43--infected cells of translatable mRNA for many prereplicative genes after product synthesis ceased indicates that the impairment in protein synthesis is not due solely to regA-mediated messenger degradation or modification. Rather, the results suggest that the regA gene product may act either by interfering with early mRNA polypeptide chain initiation or by promoting prereplicative polysome dissociation.", "contents": "Level of specific prereplicative mRNA's during bacteriophage T4 regA-, 43- and T4 43- infection of Escherichia coli B. The role of the T4 bacteriophage regA gene in stabilizing early mRNA was investigated by assaying the level of functional mRNA from eight prereplicative genes (56 [dCMP hydroxymethylase], cd [dCMP deaminase], 1 [deoxynucleotide kinase], rIIA, rIIB, 46 [DNA arrest], and 45) during extended infection of Escherichia coli B with T4 regA-, 43- and T4 43- bacteriophage. The above gene-specific transcripts in RNA isolated from infected cells were quantitated by translation with an E. coli B cell-free system. Conditions were chosen to insure that the amount of gene product formed in vitro, measured either as an enzyme activity or as a radioactive band in acrylamide gel, was directly proportional to the level of mRNA present. The failure of T4 regA-, 43- phage to terminate prereplicative synthesis (Wiberg et al., 1973) resulted in an enhanced production of many early gene products over those formed during T4 43- infection. This increase did not appear to be associated with an increment in mRNA levels, since in the present study gene-specific early mRNA's were found to be only marginally elevated and slightly more stable in T4 regA-, 43-- than in T4 43--infected cells. Of interest was the observation that significant quantities of all of the mRNA's studied; with the exception of those from genes 45 and 46, could be isolated from T4 43--infected cells after synthesis of the respective gene products had ceased. On termination of normal prereplicative synthesis during infection with T4 43- phage, polyribosomes were found to be dissociated completely, a finding which suggests that the residual mRNA present in these cells is free in the cytoplasm. The persistence in T4 43--infected cells of translatable mRNA for many prereplicative genes after product synthesis ceased indicates that the impairment in protein synthesis is not due solely to regA-mediated messenger degradation or modification. Rather, the results suggest that the regA gene product may act either by interfering with early mRNA polypeptide chain initiation or by promoting prereplicative polysome dissociation."} {"id": "PMID:176431", "title": "Hydrodynamic diameters of murine mammary, Rous sarcoma, and feline leukemia RNA tumor viruses: studies by laser beat frequency light-scattering spectroscopy and electron microscopy.", "content": "We have studied purified preparations of murine mammary tumor virus (MuMTV), Rous sarcoma virus (RSV; Prague strain), and feline leukemia virus (FeLV) by laser beat frequency light-scattering spectroscopy, ultra-centrifugation, and electron microscopy. The laser beat frequency light-scattering spectroscopy measurements yield the light-scattering intensity, weighted diffusion coefficients. The corresponding average hydrodynamic diameters, as calculated from the diffusion coefficients by the Stokes-Einstein equation for MuMTV, RSV, and FeLV, respectively, are: 144 +/- 6 nm, 147 +/- 7 nm, and 168 +/- 6 nm. Portions of the purified RSV and MuMTV preparations, from which light-scattering samples were obtained, and portions of the actual FeLV light-scattering samples were examined by negatively stained, catalase crystal-calibrated electron microscopy. The light-scattering intensity weighted averages of the electron micrograph size distributions were calculated by weighing each size by its theoretical relative scattering intensity, as obtained from published tables computed according to the Mie scattering theory. These averages and the experimentally observed hydrodynamic diameters agreed to within +/- 5%, which is the combined experimental error in the electron microscopic and light-scattering techniques. We conclude that the size distributions of singlet particles observed in the electron micrographs are statistically true representations of the sedimentation-purified solution size distributions. The sedimentation coefficients (S20, w) for MuMTV, RSV, and FeLV, respectively, are: 595 +/- 29S, 689 +/- 35S, and 880 +/- 44S. Virus partial specific volumes were taken as the reciprocals of the buoyant densities, determined in sucrose density gradients. The Svedberg equation was used to calculate particle weights from the measured diffusion and sedimentation coefficients. The particle weights for MuMTV, RSV, and FeLV, respectively, are: (3.17 +/- 0.32) x 10(8), (4.17 +/- 0.42) x 10(8), and (5.50 +/- 0.55) x 10(8) daltons.", "contents": "Hydrodynamic diameters of murine mammary, Rous sarcoma, and feline leukemia RNA tumor viruses: studies by laser beat frequency light-scattering spectroscopy and electron microscopy. We have studied purified preparations of murine mammary tumor virus (MuMTV), Rous sarcoma virus (RSV; Prague strain), and feline leukemia virus (FeLV) by laser beat frequency light-scattering spectroscopy, ultra-centrifugation, and electron microscopy. The laser beat frequency light-scattering spectroscopy measurements yield the light-scattering intensity, weighted diffusion coefficients. The corresponding average hydrodynamic diameters, as calculated from the diffusion coefficients by the Stokes-Einstein equation for MuMTV, RSV, and FeLV, respectively, are: 144 +/- 6 nm, 147 +/- 7 nm, and 168 +/- 6 nm. Portions of the purified RSV and MuMTV preparations, from which light-scattering samples were obtained, and portions of the actual FeLV light-scattering samples were examined by negatively stained, catalase crystal-calibrated electron microscopy. The light-scattering intensity weighted averages of the electron micrograph size distributions were calculated by weighing each size by its theoretical relative scattering intensity, as obtained from published tables computed according to the Mie scattering theory. These averages and the experimentally observed hydrodynamic diameters agreed to within +/- 5%, which is the combined experimental error in the electron microscopic and light-scattering techniques. We conclude that the size distributions of singlet particles observed in the electron micrographs are statistically true representations of the sedimentation-purified solution size distributions. The sedimentation coefficients (S20, w) for MuMTV, RSV, and FeLV, respectively, are: 595 +/- 29S, 689 +/- 35S, and 880 +/- 44S. Virus partial specific volumes were taken as the reciprocals of the buoyant densities, determined in sucrose density gradients. The Svedberg equation was used to calculate particle weights from the measured diffusion and sedimentation coefficients. The particle weights for MuMTV, RSV, and FeLV, respectively, are: (3.17 +/- 0.32) x 10(8), (4.17 +/- 0.42) x 10(8), and (5.50 +/- 0.55) x 10(8) daltons."} {"id": "PMID:176432", "title": "High-titer replication of nondefective Sendai virus in MDBK cells.", "content": "Egg-grown Sendai virus was adapted to growth in a bovine kidney cell line (MDBK cells) by serial passage under defined conditions. The adapted virus contained only 50S RNA and was highly infectious for MDBK cells. Infection of these cells with a high multiplicity of adapted virus resulted in a yield of 10(8) MDBK-infectious units/ml by 18 h, accompanied by severe cytopathic changes in the host. Cell fusion did not occur. Examination of the proteins of the adapted virus revealed that despite the high infectivity of this virus for MDBK cells the virions contained considerable quantities of Fo, the precursor to the F glycoprotein that is responsible for cell fusion and high infectivity in other systems.", "contents": "High-titer replication of nondefective Sendai virus in MDBK cells. Egg-grown Sendai virus was adapted to growth in a bovine kidney cell line (MDBK cells) by serial passage under defined conditions. The adapted virus contained only 50S RNA and was highly infectious for MDBK cells. Infection of these cells with a high multiplicity of adapted virus resulted in a yield of 10(8) MDBK-infectious units/ml by 18 h, accompanied by severe cytopathic changes in the host. Cell fusion did not occur. Examination of the proteins of the adapted virus revealed that despite the high infectivity of this virus for MDBK cells the virions contained considerable quantities of Fo, the precursor to the F glycoprotein that is responsible for cell fusion and high infectivity in other systems."} {"id": "PMID:176433", "title": "Kinetics of utilization of Sendai virus RNA and protein in the process of virion assembly.", "content": "The synthesis of the 50S genomic RNA and strucural proteins of Sendai virus was examined with respect to their utilization in virus assembly. It was found that during a single cycle of infection, 50S RNA was synthesized before the structural proteins and that both RNA and protein were synthesized 2 to 4 h before their appearance in released virions. Pulse-chase labeling indicated that the NP and P proteins synthesized early and the M and F proteins synthesized late were preferentially incorporated into virus relative to the other viral proteins. The kinetics of incorporation of pulse-labeled NP protein suggested that it was withdrawn from a relatively large pool whereas the M protein appeared to be present in a relatively small pool in the cytoplasm. Further, it was possible to chase pulse-labeled M protein, but not NP protein, from the cell during an 8-h time period.", "contents": "Kinetics of utilization of Sendai virus RNA and protein in the process of virion assembly. The synthesis of the 50S genomic RNA and strucural proteins of Sendai virus was examined with respect to their utilization in virus assembly. It was found that during a single cycle of infection, 50S RNA was synthesized before the structural proteins and that both RNA and protein were synthesized 2 to 4 h before their appearance in released virions. Pulse-chase labeling indicated that the NP and P proteins synthesized early and the M and F proteins synthesized late were preferentially incorporated into virus relative to the other viral proteins. The kinetics of incorporation of pulse-labeled NP protein suggested that it was withdrawn from a relatively large pool whereas the M protein appeared to be present in a relatively small pool in the cytoplasm. Further, it was possible to chase pulse-labeled M protein, but not NP protein, from the cell during an 8-h time period."} {"id": "PMID:176434", "title": "Simian virus 40 DNA replication: characterization of gaps in the termination region.", "content": "A class of precursor DNA (pDNA) II molecules has been identified as the immediate precursor of simian virus 40 DNA I. A pDNA II molecule contains a strand of newly synthesized DNA with an interruption located in the region where DNA synthesis terminates (4). These pDNA II molecules have been isolated and further characterized. They are converted to covalently closed structures (simian virus 40 DNA I) only when they are treated in vitro with both T4 DNA polymerase and Escherichia coli ligase. After in vitro repair of pDNA II with T4 DNA polymerase and nucleoside triphosphates, approximately 7 mol of alpha-[32P]dATP is incorporated per mol of DNA II. Alkaline sucrose analysis of these gap-filled molecules, after they have been cleaved with Eco RI restriction endonuclease, has demonstrated that gaps are specifically located in the termination region. alpha-[32P]dATP is incorporated equally into the two labeled products that are generated by RI cleavage of these molecules. This indicates the presence of gaps in both the newly synthesized plus the minus strands. Electrophoretic analysis of the gap-filled molecules, after they have been cleaved with endonuclease Hind, has shown that gaps are localized in Hind fragments G and B and to a minor degree in fragment J. pDNA II molecules have the following properties. There is a gap in the newly synthesized linear DNA strand contained in the pDNA II molecule. Nicked pDNA II molecules cannot be detected. The two molecules that arise by segregation contain gaps in both of the complementary strands. Based on the amount of alpha-[32P]dATP incorporated and the rate of exonuclease III digestion of gap-filled molecules, it is estimated that the size of the gaps is between 22 and 73 nucleotides. Models for termination of DNA synthesis are proposed based on these findings.", "contents": "Simian virus 40 DNA replication: characterization of gaps in the termination region. A class of precursor DNA (pDNA) II molecules has been identified as the immediate precursor of simian virus 40 DNA I. A pDNA II molecule contains a strand of newly synthesized DNA with an interruption located in the region where DNA synthesis terminates (4). These pDNA II molecules have been isolated and further characterized. They are converted to covalently closed structures (simian virus 40 DNA I) only when they are treated in vitro with both T4 DNA polymerase and Escherichia coli ligase. After in vitro repair of pDNA II with T4 DNA polymerase and nucleoside triphosphates, approximately 7 mol of alpha-[32P]dATP is incorporated per mol of DNA II. Alkaline sucrose analysis of these gap-filled molecules, after they have been cleaved with Eco RI restriction endonuclease, has demonstrated that gaps are specifically located in the termination region. alpha-[32P]dATP is incorporated equally into the two labeled products that are generated by RI cleavage of these molecules. This indicates the presence of gaps in both the newly synthesized plus the minus strands. Electrophoretic analysis of the gap-filled molecules, after they have been cleaved with endonuclease Hind, has shown that gaps are localized in Hind fragments G and B and to a minor degree in fragment J. pDNA II molecules have the following properties. There is a gap in the newly synthesized linear DNA strand contained in the pDNA II molecule. Nicked pDNA II molecules cannot be detected. The two molecules that arise by segregation contain gaps in both of the complementary strands. Based on the amount of alpha-[32P]dATP incorporated and the rate of exonuclease III digestion of gap-filled molecules, it is estimated that the size of the gaps is between 22 and 73 nucleotides. Models for termination of DNA synthesis are proposed based on these findings."} {"id": "PMID:176435", "title": "Immunocytochemical localization of simian virus 40 T antigen with peroxidase-labeled antibody fragments.", "content": "T antigen was localized in simian virus 40 lytically infected and transformed cells by Fab' antibody conjugates at the ultrastructural level. This virus-specific protein appeared in the cytoplasm of permissive cells as early as 3 h after infection. At later time intervals, the T antigen was localized in both the cytoplasm and nucleus and finally (24 h) in the nucleus. These results suggest a synthesis of T antigen on cytoplasmic ribosomes, with subsequent transfer to the nucleus.", "contents": "Immunocytochemical localization of simian virus 40 T antigen with peroxidase-labeled antibody fragments. T antigen was localized in simian virus 40 lytically infected and transformed cells by Fab' antibody conjugates at the ultrastructural level. This virus-specific protein appeared in the cytoplasm of permissive cells as early as 3 h after infection. At later time intervals, the T antigen was localized in both the cytoplasm and nucleus and finally (24 h) in the nucleus. These results suggest a synthesis of T antigen on cytoplasmic ribosomes, with subsequent transfer to the nucleus."} {"id": "PMID:176436", "title": "Characterization of Epstein-Barr virus antigens. I. Biochemical analysis of the complement-fixing soluble antigen and relationship with Epstein-Barr virus-associated nuclear antigen.", "content": "The Epstein-Barr virus-soluble (S) antigen extracted from RAJI cells was characterized by sucrose gradient centrifugation, gel filtration, and ion-exchange chromatography. The sedimentation coefficient was estimated to be 8.5S corresponding to a molecular weight of 180,000. The S antigen binds to DEAE-A25 ion exchanger from which it can be eluted with 0.3 M NaCl in Tris buffer (pH 7.2). All fractions which contained complement-fixing S antigen also inhibited the anticomplement immunofluorescence reaction as used to detect the Epstein-Barr virus-associated nuclear antigen. These results are consistent with the hypothesis that the S and Epstein-Barr virus-associated nuclear antigens are either a single antigen or that both activities are present on the same molecule.", "contents": "Characterization of Epstein-Barr virus antigens. I. Biochemical analysis of the complement-fixing soluble antigen and relationship with Epstein-Barr virus-associated nuclear antigen. The Epstein-Barr virus-soluble (S) antigen extracted from RAJI cells was characterized by sucrose gradient centrifugation, gel filtration, and ion-exchange chromatography. The sedimentation coefficient was estimated to be 8.5S corresponding to a molecular weight of 180,000. The S antigen binds to DEAE-A25 ion exchanger from which it can be eluted with 0.3 M NaCl in Tris buffer (pH 7.2). All fractions which contained complement-fixing S antigen also inhibited the anticomplement immunofluorescence reaction as used to detect the Epstein-Barr virus-associated nuclear antigen. These results are consistent with the hypothesis that the S and Epstein-Barr virus-associated nuclear antigens are either a single antigen or that both activities are present on the same molecule."} {"id": "PMID:176437", "title": "Proposed structure of two defective viral DNA oligomers produced in 3T3 cells transformed by the ts-a mutant of polyoma virus.", "content": "The various oligomeric viral DNA species produced at 32 C by two related syblines of ts-a-transformed mouse 3T3 cells were characterized. Results from the analysis of the cleavage products observed after digestion with restriction endonucleases from Haemophilus parainfluenzae, Escherichia coli RI, and Haemophilus suis are consistent with the assumption that in both sublines, the major oligomeric component is a dimer from which a segment of different length is deleted. The major oligomeric (27S) component in subline 1 was estimated to be 1.77 times the size of the viral monomer, and the major (25.5S) component in subline 15 was estimated to be 1.54 times the size of the viral monomer. These size estimates were confirmed by electron micrograph measurements. The larger oligomers produced by both sublines were found to be multiples of the major oligomeric component of each subline.", "contents": "Proposed structure of two defective viral DNA oligomers produced in 3T3 cells transformed by the ts-a mutant of polyoma virus. The various oligomeric viral DNA species produced at 32 C by two related syblines of ts-a-transformed mouse 3T3 cells were characterized. Results from the analysis of the cleavage products observed after digestion with restriction endonucleases from Haemophilus parainfluenzae, Escherichia coli RI, and Haemophilus suis are consistent with the assumption that in both sublines, the major oligomeric component is a dimer from which a segment of different length is deleted. The major oligomeric (27S) component in subline 1 was estimated to be 1.77 times the size of the viral monomer, and the major (25.5S) component in subline 15 was estimated to be 1.54 times the size of the viral monomer. These size estimates were confirmed by electron micrograph measurements. The larger oligomers produced by both sublines were found to be multiples of the major oligomeric component of each subline."} {"id": "PMID:176438", "title": "Nuclear membrane changes in herpes simplex virus-infected BHK-21 cells as seen by freeze-fracture.", "content": "The freeze-fracture technique, which produced high-resolution replicas of large internal faces of membranes, was used for an ultrastructural study of the nuclei of herpes simplex virus-infected BHK-21 cells and mock-infected controls. Crystalline arrays of viral nucleocapsids were found in the nucleoplasm of infected cells, and numerous nuclear membrane \"blebs\" and protrusions were observed. The numerous areas of membrane distortions were not found to contain nuclear pores. In addition, specific areas of normal protein intramembranous particles are deleted from certain areas of the nuclear membrane as a result of herpes simplex virus, type 2, infection.", "contents": "Nuclear membrane changes in herpes simplex virus-infected BHK-21 cells as seen by freeze-fracture. The freeze-fracture technique, which produced high-resolution replicas of large internal faces of membranes, was used for an ultrastructural study of the nuclei of herpes simplex virus-infected BHK-21 cells and mock-infected controls. Crystalline arrays of viral nucleocapsids were found in the nucleoplasm of infected cells, and numerous nuclear membrane \"blebs\" and protrusions were observed. The numerous areas of membrane distortions were not found to contain nuclear pores. In addition, specific areas of normal protein intramembranous particles are deleted from certain areas of the nuclear membrane as a result of herpes simplex virus, type 2, infection."} {"id": "PMID:176439", "title": "DNA-negative temperature-sensitive mutants of herpes simplex virus type 1: patterns of viral DNA synthesis after temperature shift-up.", "content": "Temperature-sensitive mutants of herpes simplex virus type 1 belonging to four DNA- complementation groups exhibited two distinct patterns of viral DNA synthesis after shift-up to the nonpermissive temperature. In cultures infected with mutants belonging to complementation groups A, C, and D, little or no viral DNA was synthesized after shift-up. In cultures infected with a mutant in complementation group B, nearly normal amounts of viral DNA were synthesized after shift-up.", "contents": "DNA-negative temperature-sensitive mutants of herpes simplex virus type 1: patterns of viral DNA synthesis after temperature shift-up. Temperature-sensitive mutants of herpes simplex virus type 1 belonging to four DNA- complementation groups exhibited two distinct patterns of viral DNA synthesis after shift-up to the nonpermissive temperature. In cultures infected with mutants belonging to complementation groups A, C, and D, little or no viral DNA was synthesized after shift-up. In cultures infected with a mutant in complementation group B, nearly normal amounts of viral DNA were synthesized after shift-up."} {"id": "PMID:176440", "title": "Herpesvirus proteins: induction of nucleoside phosphotransferase activity after herpes simplex virus infection.", "content": "After herpes simplex virus infection of hamster kidney cells there is an induction of nucleoside phosphotransferase activity which can utilize AMP as phosphate donor. The activity is immunologically specific for the infected cell and is induced concomitantly with the virus-coded pyrimidine deoxynucleoside kinase activity. Phosphotransferase activity is not induced in cells lacking both thymidine and deoxycytidine kinase activity.", "contents": "Herpesvirus proteins: induction of nucleoside phosphotransferase activity after herpes simplex virus infection. After herpes simplex virus infection of hamster kidney cells there is an induction of nucleoside phosphotransferase activity which can utilize AMP as phosphate donor. The activity is immunologically specific for the infected cell and is induced concomitantly with the virus-coded pyrimidine deoxynucleoside kinase activity. Phosphotransferase activity is not induced in cells lacking both thymidine and deoxycytidine kinase activity."} {"id": "PMID:176441", "title": "Complementation between BK human papovavirus and a simian virus 40 tsA mutant.", "content": "Complementation tests between BK human papovavirus and SV40 temperature-sensitive mutants tsA58 and tsB11 were performed. Under the reported experimental conditions, BKV complemented the \"early\" mutant tsA58 but failed to complement the \"late\" mutant tsB11.", "contents": "Complementation between BK human papovavirus and a simian virus 40 tsA mutant. Complementation tests between BK human papovavirus and SV40 temperature-sensitive mutants tsA58 and tsB11 were performed. Under the reported experimental conditions, BKV complemented the \"early\" mutant tsA58 but failed to complement the \"late\" mutant tsB11."} {"id": "PMID:176442", "title": "Polyoma and cell DNA synthesis in mouse L cells temperature sensitive for the replication of cell DNA.", "content": "Polyoma (Py) virus multiplies, at 34 and 38.5 C, in wild-type (WT-4) and in ts A1S9 mouse L cells, which are temperature sensitive for growth and for DNA replication (R. Sheinin, 1976; L. H. Thompson et al., 1970). De novo synthesis of double-stranded, fully covalently closed Py DNA has been shown to proceed by semiconservative replication in WT-4 and ts A1S9 cells at the permissive and nonpermissive temperatures. Cell DNA is made late during infection, by both cell types and at both temperatures. Semiconservative replication of cell DNA proceeds in Py-infected WT-4 cells incubated at 34 or at 38.5 C and in Py-infected ts A1S9 cells incubated at 34 C. In virus-infected ts A1S9 cells incubated at 38.5 C, cell DNA synthesis appears to proceed almost entirely by a process analogous to repair replication. The inability of ts A1S9 cells to produce large-molecular-weight chromosomal DNA strands, at 38.5 C, by the normal mechanism is not overcome by Py infection.", "contents": "Polyoma and cell DNA synthesis in mouse L cells temperature sensitive for the replication of cell DNA. Polyoma (Py) virus multiplies, at 34 and 38.5 C, in wild-type (WT-4) and in ts A1S9 mouse L cells, which are temperature sensitive for growth and for DNA replication (R. Sheinin, 1976; L. H. Thompson et al., 1970). De novo synthesis of double-stranded, fully covalently closed Py DNA has been shown to proceed by semiconservative replication in WT-4 and ts A1S9 cells at the permissive and nonpermissive temperatures. Cell DNA is made late during infection, by both cell types and at both temperatures. Semiconservative replication of cell DNA proceeds in Py-infected WT-4 cells incubated at 34 or at 38.5 C and in Py-infected ts A1S9 cells incubated at 34 C. In virus-infected ts A1S9 cells incubated at 38.5 C, cell DNA synthesis appears to proceed almost entirely by a process analogous to repair replication. The inability of ts A1S9 cells to produce large-molecular-weight chromosomal DNA strands, at 38.5 C, by the normal mechanism is not overcome by Py infection."} {"id": "PMID:176443", "title": "Synthesis of complementary RNA containing polyadenylic acid by Sendai virions in vitro.", "content": "Sendai virus synthesized, in vitro, [32P]AMP- and [3H]AMP-labeled RNA that ranged in size from 3 to 25S with major peaks at 7S and 13S. Both labeled products were predominantly single-stranded RNA and were complementary in base sequence to 50S virion RNA. Passage of the 3 to 25S in vitro RNA transcripts through a polyuridylic acid-cellulose column revealed that only the larger (predominantly 18S) RNA transcripts contained polyadenylic acid[poly(A)] segments capable of binding to the column. After treatment with a combination of RNase A and T1, the majority of the in vitro poly(A) sedimented at 6S although the product ranged in size from 3 to 9S. Proof that the RNase-resistant material was indeed poly(A) was obtained by nearest-neighbor analysis when 95% of the radioactivity was recovered in AMP.", "contents": "Synthesis of complementary RNA containing polyadenylic acid by Sendai virions in vitro. Sendai virus synthesized, in vitro, [32P]AMP- and [3H]AMP-labeled RNA that ranged in size from 3 to 25S with major peaks at 7S and 13S. Both labeled products were predominantly single-stranded RNA and were complementary in base sequence to 50S virion RNA. Passage of the 3 to 25S in vitro RNA transcripts through a polyuridylic acid-cellulose column revealed that only the larger (predominantly 18S) RNA transcripts contained polyadenylic acid[poly(A)] segments capable of binding to the column. After treatment with a combination of RNase A and T1, the majority of the in vitro poly(A) sedimented at 6S although the product ranged in size from 3 to 9S. Proof that the RNase-resistant material was indeed poly(A) was obtained by nearest-neighbor analysis when 95% of the radioactivity was recovered in AMP."} {"id": "PMID:176444", "title": "Quantitation of the viral DNA present in cells transformed by UV-irradiated herpes simplex virus.", "content": "Two cell lines biochemically transformed by UV-irradiated herpes simplex virus (HSV) each contain virus DNA. A comparison of the kinetics of reassociation of 3H-labeled HSV DNA in the presence and absence of either clone 139 (HSV-1 transformed) or clone 207 (HSV-2 transformed) DNA showed that the presence of transformed cell DNA increased the rate of reassociation of approximately 10% of the viral genome while having no effect on the remaining 90%. The Cot1/2 of this reaction was approximately 1,000 in each cell type, as compared to approximately 3,000 for the cellular unique sequences. These results suggest the presence of four to six copies of a 10% fragment of the virus DNA per cell. The DNA from a hamster fibroblast cell line morphologically transformed by UV-irradiated HSV-2 (333-8-9) did not affect the rate of reassociation of HSV-2 DNA, indicating that these cells had less than 3% of a viral genome present.", "contents": "Quantitation of the viral DNA present in cells transformed by UV-irradiated herpes simplex virus. Two cell lines biochemically transformed by UV-irradiated herpes simplex virus (HSV) each contain virus DNA. A comparison of the kinetics of reassociation of 3H-labeled HSV DNA in the presence and absence of either clone 139 (HSV-1 transformed) or clone 207 (HSV-2 transformed) DNA showed that the presence of transformed cell DNA increased the rate of reassociation of approximately 10% of the viral genome while having no effect on the remaining 90%. The Cot1/2 of this reaction was approximately 1,000 in each cell type, as compared to approximately 3,000 for the cellular unique sequences. These results suggest the presence of four to six copies of a 10% fragment of the virus DNA per cell. The DNA from a hamster fibroblast cell line morphologically transformed by UV-irradiated HSV-2 (333-8-9) did not affect the rate of reassociation of HSV-2 DNA, indicating that these cells had less than 3% of a viral genome present."} {"id": "PMID:176445", "title": "Factors involved in the generation and replication of rhabdovirus defective T particles.", "content": "Previous indications that cloned B virions might be genetically predisposed to generate a particular defective T particle are shown to be inaccurate. T particle generation was found to be a much more random process than was previously believed. We show that the previously observed generation of particular sizes of T particles by B virion pools is due to the random generation of T particles during preparation of first-passage pools of cloned B virions, and these breed true during the additional passages needed to produce visible quantities of T particles. It is also shown that different host cell lines selectively amplify different T particles, suggesting a strong role of host cell factors in T particle replication. Surprisingly, our line of HeLa cells did not generate or replicate detectable T particles of vesicular stomatitis virus (VSV) Indiana after either serial undiluted passage or direct addition of T particles, even though the added T particles strongly interfered with B virion replication. In contrast to VSV, rabies virus generates large amounts of T particles during the first passage of cloned B virions, and every rabies-infected baby hamster kidney-21 cell culture evolves into a persistent carrier state. We find that T particle RNA is biologically inactive although T particle nucleocapsid ribonucleoprotein replicates and interferes in cells coinfected with B virions. Efforts to study the mechanism of T particle generation by in vitro attempts to generate T particles or modify their size (using sheared ribonucleoprotein or chemical or UV mutagenesis) were unsuccessful. The kinetics of UV and nitrous acid inactivation of T particles indicate a smaller target size relative to B virions, even after correcting for lengths of RNA molecules. The intercalating dye proflavine does not photosensitize VSV B virions or T particles when present during replication, indicating that there is little or no RNA base pairing in the helical nucleocapsids of either.", "contents": "Factors involved in the generation and replication of rhabdovirus defective T particles. Previous indications that cloned B virions might be genetically predisposed to generate a particular defective T particle are shown to be inaccurate. T particle generation was found to be a much more random process than was previously believed. We show that the previously observed generation of particular sizes of T particles by B virion pools is due to the random generation of T particles during preparation of first-passage pools of cloned B virions, and these breed true during the additional passages needed to produce visible quantities of T particles. It is also shown that different host cell lines selectively amplify different T particles, suggesting a strong role of host cell factors in T particle replication. Surprisingly, our line of HeLa cells did not generate or replicate detectable T particles of vesicular stomatitis virus (VSV) Indiana after either serial undiluted passage or direct addition of T particles, even though the added T particles strongly interfered with B virion replication. In contrast to VSV, rabies virus generates large amounts of T particles during the first passage of cloned B virions, and every rabies-infected baby hamster kidney-21 cell culture evolves into a persistent carrier state. We find that T particle RNA is biologically inactive although T particle nucleocapsid ribonucleoprotein replicates and interferes in cells coinfected with B virions. Efforts to study the mechanism of T particle generation by in vitro attempts to generate T particles or modify their size (using sheared ribonucleoprotein or chemical or UV mutagenesis) were unsuccessful. The kinetics of UV and nitrous acid inactivation of T particles indicate a smaller target size relative to B virions, even after correcting for lengths of RNA molecules. The intercalating dye proflavine does not photosensitize VSV B virions or T particles when present during replication, indicating that there is little or no RNA base pairing in the helical nucleocapsids of either."} {"id": "PMID:176446", "title": "Further characterization of intracytoplasmic A particle-associated DNA.", "content": "A DNA species with buoyant densities greater than mouse cellular DNA was found associated with intracytoplasmic A particles (CAP) isolated from mouse mammary tumor virus-infected mouse mammary tumors and mouse Leydig cell tumors which produce CAP but no complete mouse mammary tumor virus virions. This DNA species was absent in identically prepared tissue fractions from tumors which did not contain CAP. Treatment of CAP-associated DNA with pancreatic RNase A did not alter the buoyant density although a reduction in apparent molecular weight (broadening of the DNA band at equilibrium) was observed upon analytical equilibrium sedimentation in CsCl. The molecular weight of untreated CAP-associated DNA was estimated to range from 0.8 x 10(6) to 3.1 x 10(6). Base composition analysis showed CAP-DNA to possess an approximate guanine plus cytosine content of 38%. Ninety percent of CAP-associated DNA eluted as single-stranded molecules upon hydroxyapatite column chromatography, a characteristic that accounts in part for its higher buoyant density in neutral CsCl compared to native double-stranded mouse DNA. In two preparations, CAP-DNA had a sedimentation coefficient of 7 to 8S.", "contents": "Further characterization of intracytoplasmic A particle-associated DNA. A DNA species with buoyant densities greater than mouse cellular DNA was found associated with intracytoplasmic A particles (CAP) isolated from mouse mammary tumor virus-infected mouse mammary tumors and mouse Leydig cell tumors which produce CAP but no complete mouse mammary tumor virus virions. This DNA species was absent in identically prepared tissue fractions from tumors which did not contain CAP. Treatment of CAP-associated DNA with pancreatic RNase A did not alter the buoyant density although a reduction in apparent molecular weight (broadening of the DNA band at equilibrium) was observed upon analytical equilibrium sedimentation in CsCl. The molecular weight of untreated CAP-associated DNA was estimated to range from 0.8 x 10(6) to 3.1 x 10(6). Base composition analysis showed CAP-DNA to possess an approximate guanine plus cytosine content of 38%. Ninety percent of CAP-associated DNA eluted as single-stranded molecules upon hydroxyapatite column chromatography, a characteristic that accounts in part for its higher buoyant density in neutral CsCl compared to native double-stranded mouse DNA. In two preparations, CAP-DNA had a sedimentation coefficient of 7 to 8S."} {"id": "PMID:176447", "title": "Quantitation of bovine papilloma viral DNA in viral-induced tumors.", "content": "Bovine papilloma virus (BPV) DNA was labeled in vitro under conditions of repair synthesis and subsequently used as a \"probe\" in DNA-DNA reassociation studies to detect BPV-specific DNA sequences in a viral-induced calf meningioma and hamster fibroma. In vitro labeled BPV DNA had denaturation characteristics expected for duplex DNA and denatured DNA reassociated with apparent second-order kinetics. Analysis of in vitro labeled BPV DNA reassociation rates in the presence of excess tumor DNA revealed that the calf meningioma contained approximately 700 to 800 BPV genome equivalents per diploid cell whereas the hamster fibroma contained about 150 incomplete BPV genome equivalents per diploid cell. Thermal denaturation of in vitro labeled BPV DNA which reassociated in the presence of the two tumor DNA preparations indicated less than 1.5% base pair mismatching.", "contents": "Quantitation of bovine papilloma viral DNA in viral-induced tumors. Bovine papilloma virus (BPV) DNA was labeled in vitro under conditions of repair synthesis and subsequently used as a \"probe\" in DNA-DNA reassociation studies to detect BPV-specific DNA sequences in a viral-induced calf meningioma and hamster fibroma. In vitro labeled BPV DNA had denaturation characteristics expected for duplex DNA and denatured DNA reassociated with apparent second-order kinetics. Analysis of in vitro labeled BPV DNA reassociation rates in the presence of excess tumor DNA revealed that the calf meningioma contained approximately 700 to 800 BPV genome equivalents per diploid cell whereas the hamster fibroma contained about 150 incomplete BPV genome equivalents per diploid cell. Thermal denaturation of in vitro labeled BPV DNA which reassociated in the presence of the two tumor DNA preparations indicated less than 1.5% base pair mismatching."} {"id": "PMID:176448", "title": "Genome localization of simian virus 40 RNA species.", "content": "The topographical locations on the simian virus 40 (SV40) genome of the templates for virus-specific RNA species present late in the lytic infection were determined by RNA-DNA hybridization experiments with the Hind restriction enzyme fragments. Two classes of late virus-specific cytoplasmic mRNA's can be separated on the basis of either sedimentation properties in neutral sucrose or electrophoretic mobility in polyacrylamide gels. In the 16S class, two species of RNA were identified by hybridization experiments. One of these species was complementary to sequences of the early template on the minus (E) strand (0.175 to 0.655 map units), and the other more abundant species was complementary to sequences present in the late template on the plus (L) strand (0.655 to 0.175 map units). In addition two species were detected in the 16S class of late cytoplasmic virus-specific mRNA. One of these species was the major late RNA detected and consisted of a polyadenylated transcript complementary to the plus (L) DNA strands of Hind fragments K, F, J, and G (0.945 to 0.175 map units). This species appears to specify the major capsid protein (VP1). A less abundant nonpolyadenylated 16S RNA species complementary to the plus (L) strands of Hind fragments C, D, and E (0.655 to 0.945 map units) may result from post-transcriptional processing or nonspecific degradation of the 19S viral RNA complementary to the plus (L) strand.", "contents": "Genome localization of simian virus 40 RNA species. The topographical locations on the simian virus 40 (SV40) genome of the templates for virus-specific RNA species present late in the lytic infection were determined by RNA-DNA hybridization experiments with the Hind restriction enzyme fragments. Two classes of late virus-specific cytoplasmic mRNA's can be separated on the basis of either sedimentation properties in neutral sucrose or electrophoretic mobility in polyacrylamide gels. In the 16S class, two species of RNA were identified by hybridization experiments. One of these species was complementary to sequences of the early template on the minus (E) strand (0.175 to 0.655 map units), and the other more abundant species was complementary to sequences present in the late template on the plus (L) strand (0.655 to 0.175 map units). In addition two species were detected in the 16S class of late cytoplasmic virus-specific mRNA. One of these species was the major late RNA detected and consisted of a polyadenylated transcript complementary to the plus (L) DNA strands of Hind fragments K, F, J, and G (0.945 to 0.175 map units). This species appears to specify the major capsid protein (VP1). A less abundant nonpolyadenylated 16S RNA species complementary to the plus (L) strands of Hind fragments C, D, and E (0.655 to 0.945 map units) may result from post-transcriptional processing or nonspecific degradation of the 19S viral RNA complementary to the plus (L) strand."} {"id": "PMID:176449", "title": "Regulatory mechanism of simian virus 40 gene expression in permissive and in nonpermissive cells.", "content": "Primary or continuous lines of mouse cells (3T3) are nonpermissive for simian virus 40 (SV40). Abortively infected cells synthesize tumor antigen (T antigen but not viral DNA and virus capsid protein (V antigen). V antigen, however, was obtained when SV40 DNA was injected into 3T3 cells. This late gene expression also appears to be correlated with the quantity of injected DNA molecules per 3T3 cell. T antigen formation can be detected after microinjection of only 1 to 2 DNA molecules, but the intensity of intranuclear T antigen fluorescence is significantly brighter with injection of higher concentrations of viral DNA. In permissive cells (TC7), early and late SV40 gene expression is directly related to the number of injected molecules. Microinjection of 1DNA molecule induced T and V antigen formation with the same efficiency as microinjection of 2,000 to 4,000 molecules. The question of weather late SV40 gene expression is directly related to the quantity of an early virus-specific product was approached by microinjection of early SV40 complementary RNA together with small amounts of viral DNA. V antigen was obtained in a high proportion of recipient 3T3 cells at conditions where microinjection of viral DNA alone induced T but not V antigen synthesis.", "contents": "Regulatory mechanism of simian virus 40 gene expression in permissive and in nonpermissive cells. Primary or continuous lines of mouse cells (3T3) are nonpermissive for simian virus 40 (SV40). Abortively infected cells synthesize tumor antigen (T antigen but not viral DNA and virus capsid protein (V antigen). V antigen, however, was obtained when SV40 DNA was injected into 3T3 cells. This late gene expression also appears to be correlated with the quantity of injected DNA molecules per 3T3 cell. T antigen formation can be detected after microinjection of only 1 to 2 DNA molecules, but the intensity of intranuclear T antigen fluorescence is significantly brighter with injection of higher concentrations of viral DNA. In permissive cells (TC7), early and late SV40 gene expression is directly related to the number of injected molecules. Microinjection of 1DNA molecule induced T and V antigen formation with the same efficiency as microinjection of 2,000 to 4,000 molecules. The question of weather late SV40 gene expression is directly related to the quantity of an early virus-specific product was approached by microinjection of early SV40 complementary RNA together with small amounts of viral DNA. V antigen was obtained in a high proportion of recipient 3T3 cells at conditions where microinjection of viral DNA alone induced T but not V antigen synthesis."} {"id": "PMID:176450", "title": "Analysis of structural proteins of purified murine cytomegalovirus.", "content": "Murine cytomegalovirus propagated in mouse embryo fibroblasts was purified by the following procedures. (i) Extracellular virus was concentrated by centrifugation at 100,000 x g for 90 min. (ii) The concentrated virus was passed through a Bio-Rad Bio-Gel A-15m column to eliminate contaminating materials smaller than 15 x 10(6) daltons. Most of the virus was recovered in the void volume of the column. (iii) Two consecutive centrifugations through 20 to 50% potassium tartrate gradients were performed. After the second tartrate gradient centrifugation, symmetrical, coinciding peaks of plaque titer, protein, and radioactivity were found at a density between 1.20 g/cm3 and 1.21 g/cm3. To establish purification criteria, virus was purified from two different mixtures: [35S]methionine-labeled extracellular virus, mixed with an equal volume of unlabeled normal culture fluid, and unlabeled extracellular virus mixed with an equal volume of [35S]methionine-labeled normal culture fluid. At the end of the procedure, the extent of purification, as judged by the ratio of cellular to viral radioactivity was at least 70-fold. Virus proteins were analyzed by electrophoresis on a 5 to 20% gradient polyacrylamide gel slab. After gel electrophoresis,, Coomassie brilliant blue staining profiles and autoradiograms of the purified virus preparations were compared. At least 33 virus structural protein bands were present. The molecular weights of these proteins ranged from 11,500 to 255,000. The sum of the molecular weights of the virus structural proteins was 2,462,000. Autoradiograms obtained from electrophoresis of purified [14C]glucosamine-labeled virus showed that at lease 6 of the 33 viral structural proteins were glycoproteins.", "contents": "Analysis of structural proteins of purified murine cytomegalovirus. Murine cytomegalovirus propagated in mouse embryo fibroblasts was purified by the following procedures. (i) Extracellular virus was concentrated by centrifugation at 100,000 x g for 90 min. (ii) The concentrated virus was passed through a Bio-Rad Bio-Gel A-15m column to eliminate contaminating materials smaller than 15 x 10(6) daltons. Most of the virus was recovered in the void volume of the column. (iii) Two consecutive centrifugations through 20 to 50% potassium tartrate gradients were performed. After the second tartrate gradient centrifugation, symmetrical, coinciding peaks of plaque titer, protein, and radioactivity were found at a density between 1.20 g/cm3 and 1.21 g/cm3. To establish purification criteria, virus was purified from two different mixtures: [35S]methionine-labeled extracellular virus, mixed with an equal volume of unlabeled normal culture fluid, and unlabeled extracellular virus mixed with an equal volume of [35S]methionine-labeled normal culture fluid. At the end of the procedure, the extent of purification, as judged by the ratio of cellular to viral radioactivity was at least 70-fold. Virus proteins were analyzed by electrophoresis on a 5 to 20% gradient polyacrylamide gel slab. After gel electrophoresis,, Coomassie brilliant blue staining profiles and autoradiograms of the purified virus preparations were compared. At least 33 virus structural protein bands were present. The molecular weights of these proteins ranged from 11,500 to 255,000. The sum of the molecular weights of the virus structural proteins was 2,462,000. Autoradiograms obtained from electrophoresis of purified [14C]glucosamine-labeled virus showed that at lease 6 of the 33 viral structural proteins were glycoproteins."} {"id": "PMID:176451", "title": "Analysis of simian virus 40 wild-type and mutant virions by agarose gel electrophoresis.", "content": "Intact wild-type simian virus 40 particles can be separated and resolved from a temperature-sensitive mutant and from a number of other viruses by agarose gel electrophoresis. The relative mobilities of the viruses appear to be a function of both virion size and surface composition. The virions of a temperature-sensitive strain of simian virus 40, tsB204, have significantly greater mobility than those of wild-type simian virus 40, when electrophoresis was conducted toward the cathode at pH 5.0. When electrophoresis was performed toward the anode at pH 7.0, TSB204 viruses have a slightly slower mobility as compared with that of the wild type. The data indicated that the virions of tsB204 have a greater positive charge at their surface than those of wild-type particles. No differences were detected in the finger print patterns of the tryptic peptides of VP1 and VP3 of these two virus strains. Although it was not possible to identify the structural polypeptide directly affected by the tsB204 mutation, we have shown that this mutation affects charge distribution on the surface of the virion.", "contents": "Analysis of simian virus 40 wild-type and mutant virions by agarose gel electrophoresis. Intact wild-type simian virus 40 particles can be separated and resolved from a temperature-sensitive mutant and from a number of other viruses by agarose gel electrophoresis. The relative mobilities of the viruses appear to be a function of both virion size and surface composition. The virions of a temperature-sensitive strain of simian virus 40, tsB204, have significantly greater mobility than those of wild-type simian virus 40, when electrophoresis was conducted toward the cathode at pH 5.0. When electrophoresis was performed toward the anode at pH 7.0, TSB204 viruses have a slightly slower mobility as compared with that of the wild type. The data indicated that the virions of tsB204 have a greater positive charge at their surface than those of wild-type particles. No differences were detected in the finger print patterns of the tryptic peptides of VP1 and VP3 of these two virus strains. Although it was not possible to identify the structural polypeptide directly affected by the tsB204 mutation, we have shown that this mutation affects charge distribution on the surface of the virion."} {"id": "PMID:176452", "title": "Proteins of Epstein-Barr virus. I. Analysis of the polypeptides of purified enveloped Epstein-Barr virus.", "content": "Epstein-Barr virus (EBV) was purified from the extracellular fluid of HR-1 and B95-8 cell lines. The preparations of purified virus consisted of enveloped particles and had EBV-specific antigneic reactivity. Comparison of the amount of labeled protein in preparations of virus purified from cultures incubated in [35S]methionine with the amount of labeled protein in preparations obtained following a mixture of unlabeled virus with [35S]methionine-labeled cellular proteins indicated that less than 2% of the labeled protein in the purified virus preparation could be attributed to contamination with labeled cellular proteins. No extraneous membranous material was seen in thin sections of the purified virus preparations. Analysis of the polypeptides of purified enveloped EBV indicated the following. (i) Eighteen polypeptides could be resolved in Coomassie brilliant blue-stained electropherograms of extracellular virus purified from HR-1 and B95-8 cultures. (ii) Thirty-three polypeptides could be resolved in fluorograms of labeled EBV purified from B95-8 cultures and subjected to electrophoresis in acrylamide gels cross-linked with diallyltartardiamide. The molecular weight of the EBV polypeptides was estimated by co-electrophoresis with the polypeptides of purified herpes simplex virus and purified polypeptides of known molecular weight to range from 28 x 10(3) to approximately 290 x 10(3) (iii) The polypeptides of EBV could be grouped by their relative molar abundancy into three classes: VP6, 7, and 27 present in high abundance; VP1, 12, 20, 23, and 29 present in moderate abundance; and a third class of less abundant polypeptides, VP4, 5, 8, 9, 10, 11, 15, 16, 21, and 22. The remainder of the polypeptides could not be precisely quantitated. (iv) The polypeptides of purified EBV, although similar in number and in range of molecular weight to the polypeptides of purified herpes simplex virus, differ sufficiently from those of herpes simplex virus so as to preclude comparison of individual polypeptide components.", "contents": "Proteins of Epstein-Barr virus. I. Analysis of the polypeptides of purified enveloped Epstein-Barr virus. Epstein-Barr virus (EBV) was purified from the extracellular fluid of HR-1 and B95-8 cell lines. The preparations of purified virus consisted of enveloped particles and had EBV-specific antigneic reactivity. Comparison of the amount of labeled protein in preparations of virus purified from cultures incubated in [35S]methionine with the amount of labeled protein in preparations obtained following a mixture of unlabeled virus with [35S]methionine-labeled cellular proteins indicated that less than 2% of the labeled protein in the purified virus preparation could be attributed to contamination with labeled cellular proteins. No extraneous membranous material was seen in thin sections of the purified virus preparations. Analysis of the polypeptides of purified enveloped EBV indicated the following. (i) Eighteen polypeptides could be resolved in Coomassie brilliant blue-stained electropherograms of extracellular virus purified from HR-1 and B95-8 cultures. (ii) Thirty-three polypeptides could be resolved in fluorograms of labeled EBV purified from B95-8 cultures and subjected to electrophoresis in acrylamide gels cross-linked with diallyltartardiamide. The molecular weight of the EBV polypeptides was estimated by co-electrophoresis with the polypeptides of purified herpes simplex virus and purified polypeptides of known molecular weight to range from 28 x 10(3) to approximately 290 x 10(3) (iii) The polypeptides of EBV could be grouped by their relative molar abundancy into three classes: VP6, 7, and 27 present in high abundance; VP1, 12, 20, 23, and 29 present in moderate abundance; and a third class of less abundant polypeptides, VP4, 5, 8, 9, 10, 11, 15, 16, 21, and 22. The remainder of the polypeptides could not be precisely quantitated. (iv) The polypeptides of purified EBV, although similar in number and in range of molecular weight to the polypeptides of purified herpes simplex virus, differ sufficiently from those of herpes simplex virus so as to preclude comparison of individual polypeptide components."} {"id": "PMID:176453", "title": "Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells.", "content": "Polypeptide precursors to the major glycoproteins specified by herpes simplex virus type 1 were identified in immunoprecipitation experiments using antisera that reacted specifically with the viral glycoproteins and their precursors. The results demonstrate that the major glycosylated proteins detected in infected cells are derived from four antigenically distinct polypeptides. Three of these polypeptides become glycosylated in two discrete stages, yielding partially glycosylated intermediates and fully glycosylated products. The final products are the predominant species detected in cytoplasmic virions and in plasma membranes. The fourth polypeptide precursor appears to acquire very little carbohydrate and differs in several respects from the other three precursors.", "contents": "Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells. Polypeptide precursors to the major glycoproteins specified by herpes simplex virus type 1 were identified in immunoprecipitation experiments using antisera that reacted specifically with the viral glycoproteins and their precursors. The results demonstrate that the major glycosylated proteins detected in infected cells are derived from four antigenically distinct polypeptides. Three of these polypeptides become glycosylated in two discrete stages, yielding partially glycosylated intermediates and fully glycosylated products. The final products are the predominant species detected in cytoplasmic virions and in plasma membranes. The fourth polypeptide precursor appears to acquire very little carbohydrate and differs in several respects from the other three precursors."} {"id": "PMID:176454", "title": "DNA polymerase activities induced by polyoma virus infection of 3T3 mouse fibroblasts.", "content": "Resting mouse 3T3 fibroblasts were stimulated to synthesize DNA either by infection with polyoma virus or by injection of fresh serum. Changes in the levels of DNA polymerase (alpha-, beta-, and gamma-enzymes) were measured in the cytoplasm and the cell nucleus. Both types of stimulation gave very similar increases for all three enzyme activities. In the cell nucleus, both alpha- and gamma-polymerases increased almost tenfold, whereas the beta-enzyme only was stimulated twofold. In the cytoplasm alpha- and gamma-polymerases increased two- to four-fold. Only insignificant amounts of the beta-enzyme were found in the cytoplasm.", "contents": "DNA polymerase activities induced by polyoma virus infection of 3T3 mouse fibroblasts. Resting mouse 3T3 fibroblasts were stimulated to synthesize DNA either by infection with polyoma virus or by injection of fresh serum. Changes in the levels of DNA polymerase (alpha-, beta-, and gamma-enzymes) were measured in the cytoplasm and the cell nucleus. Both types of stimulation gave very similar increases for all three enzyme activities. In the cell nucleus, both alpha- and gamma-polymerases increased almost tenfold, whereas the beta-enzyme only was stimulated twofold. In the cytoplasm alpha- and gamma-polymerases increased two- to four-fold. Only insignificant amounts of the beta-enzyme were found in the cytoplasm."} {"id": "PMID:176455", "title": "Protein synthesis in bacteriophage ghost-infected cells.", "content": "Escherichia coli B infected with T4 phage ghosts at 10 mM Mg2+ regains its protein synthesizing activity upon addition of ATP, GTP, and their generator to approximately 2% of the intact exponentially growing cells. In contrast to amino acid incorporation by intact cells, this system is sensitive to EDTA or low Mg2+. On the other hand, this system, differing from the regular cell-free system, does not respond to addition of soluble protein and ribonuclease. The ghost-infected cells were able to synthesize beta-galactosidase upon addition of the inducer isopropyl thiogalactoside. The initial rate of the induction was 2.6% of intact cells. For this induction, the addition of cyclic AMP, amino acids, ATP, GTP, UTP, CTP, and their generator was necessary. The induction of beta-galactosidase in these ghost-infected cells was very sensitive to the addition of EDTA, CaCl2, sulfhydryl blocking reagent, rifampin and chloramphenicol but insensitive to DNA synthesis inhibitors such as nalidixic acid and DNase.", "contents": "Protein synthesis in bacteriophage ghost-infected cells. Escherichia coli B infected with T4 phage ghosts at 10 mM Mg2+ regains its protein synthesizing activity upon addition of ATP, GTP, and their generator to approximately 2% of the intact exponentially growing cells. In contrast to amino acid incorporation by intact cells, this system is sensitive to EDTA or low Mg2+. On the other hand, this system, differing from the regular cell-free system, does not respond to addition of soluble protein and ribonuclease. The ghost-infected cells were able to synthesize beta-galactosidase upon addition of the inducer isopropyl thiogalactoside. The initial rate of the induction was 2.6% of intact cells. For this induction, the addition of cyclic AMP, amino acids, ATP, GTP, UTP, CTP, and their generator was necessary. The induction of beta-galactosidase in these ghost-infected cells was very sensitive to the addition of EDTA, CaCl2, sulfhydryl blocking reagent, rifampin and chloramphenicol but insensitive to DNA synthesis inhibitors such as nalidixic acid and DNase."} {"id": "PMID:176456", "title": "Characterization of the type and group specificities of the immune response in mice to murine leukemia viruses.", "content": "Normal sera from a variety of strains of inbred mice have precipitating antibodies to murine type C viruses that are detected by radioimmune precipitation assays. The results demonostrate that this humoral immune response is primarily directed against the AKR strain of murine leukemia virus (MuLV) proteins gp71, gp43, and p15(E). These sera also react with Friend- or Rauscher-MuLV in radioimmune precipitation assays. This reaction is not due to a separate immune response, but rather is primarily a consequence of the cross-reactivity of antibodies to the AKR strain of MuLV p15(E) with the p15(E) of these viruses. These data, using autogenous immune sera, emphasize the serological differences of the virion glycoproteins and the serological similarity of the p15(E) virion component of the viruses. Furthermore, based on the serological reactivities to the glycoproteins, the results suggest that the AKR strain of MuLV is endogenous to and expressed in mice, but that the Friend-Moloney-Rauscher virus group is not.", "contents": "Characterization of the type and group specificities of the immune response in mice to murine leukemia viruses. Normal sera from a variety of strains of inbred mice have precipitating antibodies to murine type C viruses that are detected by radioimmune precipitation assays. The results demonostrate that this humoral immune response is primarily directed against the AKR strain of murine leukemia virus (MuLV) proteins gp71, gp43, and p15(E). These sera also react with Friend- or Rauscher-MuLV in radioimmune precipitation assays. This reaction is not due to a separate immune response, but rather is primarily a consequence of the cross-reactivity of antibodies to the AKR strain of MuLV p15(E) with the p15(E) of these viruses. These data, using autogenous immune sera, emphasize the serological differences of the virion glycoproteins and the serological similarity of the p15(E) virion component of the viruses. Furthermore, based on the serological reactivities to the glycoproteins, the results suggest that the AKR strain of MuLV is endogenous to and expressed in mice, but that the Friend-Moloney-Rauscher virus group is not."} {"id": "PMID:176457", "title": "Inhibition of Epstein-Barr virus DNA synthesis and late gene expression by phosphonoacetic acid.", "content": "Growth of lymphoblastoid cells (B95-8, Raji) is not inhibited by the presence of 0.4 mM phosphonoacetic acid. The synthesis of Epstein-Barr virus (EBV) in the producer line B95-8 is completely inhibited, as shown by the total inhibition of viral capsid antigen synthesis. Early viral antigens are made normally in the presence of phosphonoacetic acid, but EBV DNA synthesis is blocked in cells entering the productive cycle. Nonproducer cells in the population replicate the resident EBV DNA by a mechanism that is resistant to phosphonoacetic acid. These results are consistant with the hypotheses that EBV DNA is replicated by two mechanisms, one in the noninduced cell and a different mechanism in the producer cell, and that prior replication of EBV DNA, probably by the second mode, is a prerequisite for late gene expression.", "contents": "Inhibition of Epstein-Barr virus DNA synthesis and late gene expression by phosphonoacetic acid. Growth of lymphoblastoid cells (B95-8, Raji) is not inhibited by the presence of 0.4 mM phosphonoacetic acid. The synthesis of Epstein-Barr virus (EBV) in the producer line B95-8 is completely inhibited, as shown by the total inhibition of viral capsid antigen synthesis. Early viral antigens are made normally in the presence of phosphonoacetic acid, but EBV DNA synthesis is blocked in cells entering the productive cycle. Nonproducer cells in the population replicate the resident EBV DNA by a mechanism that is resistant to phosphonoacetic acid. These results are consistant with the hypotheses that EBV DNA is replicated by two mechanisms, one in the noninduced cell and a different mechanism in the producer cell, and that prior replication of EBV DNA, probably by the second mode, is a prerequisite for late gene expression."} {"id": "PMID:176458", "title": "Oligosaccharide moieties of the glycoprotein of vesicular stomatitis virus.", "content": "Vesicular stomatitis virus contains a single structural glycoprotein whose carbohydrate sequences are probably specified by the host cell. The glycopeptides derived by Pronase digestion of the glycoprotein of vesicular stomatitis virus grown in HeLa cells have an average molecular weight of 1,800. There are multiple oligosaccharide chains on the vesicular stomatitis virus glycoprotein with protein-carbohydrate linkages that are cleaved only by strong alkali under reducing conditions, suggesting that they contain asparagine and N-acetylglucosamine. The oligosaccharide moieties, in addition, appear to be heterogeneous in sequence on the basis of their mobilities during electrophoresis and their sensitivities to cleavage by an endoglycosidase. The carbohydrate-peptide linkage region of the major class of oligosaccharides of the vesicular stomatitis virus glycoprotein has the proposed sequence: (see article).", "contents": "Oligosaccharide moieties of the glycoprotein of vesicular stomatitis virus. Vesicular stomatitis virus contains a single structural glycoprotein whose carbohydrate sequences are probably specified by the host cell. The glycopeptides derived by Pronase digestion of the glycoprotein of vesicular stomatitis virus grown in HeLa cells have an average molecular weight of 1,800. There are multiple oligosaccharide chains on the vesicular stomatitis virus glycoprotein with protein-carbohydrate linkages that are cleaved only by strong alkali under reducing conditions, suggesting that they contain asparagine and N-acetylglucosamine. The oligosaccharide moieties, in addition, appear to be heterogeneous in sequence on the basis of their mobilities during electrophoresis and their sensitivities to cleavage by an endoglycosidase. The carbohydrate-peptide linkage region of the major class of oligosaccharides of the vesicular stomatitis virus glycoprotein has the proposed sequence: (see article)."} {"id": "PMID:176459", "title": "Autologous immune responses to the major oncornavirus polypeptides in unmanipulated AKR/J mice.", "content": "The autologous immune response of AKR/J mice to the structural proteins of murine leukemia virus (MuLV) was examined. Immunoglobulins from the renal glomeruli were chemically eluted, separated from antigens, recovered, and tested for immunological reactivity against MuLV structural proteins. Analyzing immune precipitates obtained after mixing radiolabeled Tween-disrupted MuLV preparations with eluates from AKR/J mice on sodium dodecyl sulfategel electrophoresis, we found evidence of antibodies to the major classes of MuLV structural components: gp70, gp45, p30, and one or more proteins in the 10,000- to 15,000-dalton class. Using rate zonal centrifugation we confirmed that the eluates from AKR/J glomeruli contained antibody(s) that bound specifically to p30. These results indicate that AKR/J mice spontaneously mount immune responses against the major oncornavirus polypeptide antigens.", "contents": "Autologous immune responses to the major oncornavirus polypeptides in unmanipulated AKR/J mice. The autologous immune response of AKR/J mice to the structural proteins of murine leukemia virus (MuLV) was examined. Immunoglobulins from the renal glomeruli were chemically eluted, separated from antigens, recovered, and tested for immunological reactivity against MuLV structural proteins. Analyzing immune precipitates obtained after mixing radiolabeled Tween-disrupted MuLV preparations with eluates from AKR/J mice on sodium dodecyl sulfategel electrophoresis, we found evidence of antibodies to the major classes of MuLV structural components: gp70, gp45, p30, and one or more proteins in the 10,000- to 15,000-dalton class. Using rate zonal centrifugation we confirmed that the eluates from AKR/J glomeruli contained antibody(s) that bound specifically to p30. These results indicate that AKR/J mice spontaneously mount immune responses against the major oncornavirus polypeptide antigens."} {"id": "PMID:176460", "title": "Cellular protein synthesis shutoff by mengovirus: translation of nonviral and viral mRNA's in extracts from uninfected and infected Ehrlich ascites tumor cells.", "content": "The mechanism whereby picornaviruses inhibit host protein synthesis while their own synthetic processes proceed unabated has remained elusive. One of our approaches to this problem was to study the ability of cell-free extracts derived from uninfected and mengovirus-infected Ehrlich ascites tumor cells to translate viral and nonviral mRNA's under various conditions of incubation. Our results indicate that viral messengers (from mengovirus and encephalomyocarditis virus) and cellular messengers [L cell and Ehrlich ascites tumor poly(A)-containing mRNA's, rabbit globin mRNA, and chicken embryo lens crystallin mRNA] are translated equally well in both extracts. We also examined the simultaneous translation of viral and nonviral mRNA's in extracts from uninfected Ehrlich ascites tumor cells. Our results indicate that under certain conditions mengovirus RNA can suppress completely the translation of globin mRNA. The significance of these results in terms of the shutoff of host protein synthesis is discussed.", "contents": "Cellular protein synthesis shutoff by mengovirus: translation of nonviral and viral mRNA's in extracts from uninfected and infected Ehrlich ascites tumor cells. The mechanism whereby picornaviruses inhibit host protein synthesis while their own synthetic processes proceed unabated has remained elusive. One of our approaches to this problem was to study the ability of cell-free extracts derived from uninfected and mengovirus-infected Ehrlich ascites tumor cells to translate viral and nonviral mRNA's under various conditions of incubation. Our results indicate that viral messengers (from mengovirus and encephalomyocarditis virus) and cellular messengers [L cell and Ehrlich ascites tumor poly(A)-containing mRNA's, rabbit globin mRNA, and chicken embryo lens crystallin mRNA] are translated equally well in both extracts. We also examined the simultaneous translation of viral and nonviral mRNA's in extracts from uninfected Ehrlich ascites tumor cells. Our results indicate that under certain conditions mengovirus RNA can suppress completely the translation of globin mRNA. The significance of these results in terms of the shutoff of host protein synthesis is discussed."} {"id": "PMID:176461", "title": "Chemical modification of simian virus 40 DNA by reaction with a water-soluble carbodiimide.", "content": "Superhelical simian virus 40 (SV40) DNA I can be modified with N-cyclohexyl-N'-beta-(4 methylmorpholinium)ethylcarbodiimide (CMC). The reaction produces an increase in the sedimentation velocity of DNA I from 21 to 22.5S and a decrease in its buoyant density in CsCl from 1.694 to 1.688. A comparable shift in buoyant density is observed in a saturated ethidium bromide-cesium chloride gradient where form II, which has been exposed to CMC, shows no shift. The CsCl-buoyant density data allows us to estimate that 108 mol of CMC are bound per mol of SV40 DNA I. In the subsequent paper an alternative procedure has been used to locate CMC sites, and the extent of the regions available to bind CMC have been measured.", "contents": "Chemical modification of simian virus 40 DNA by reaction with a water-soluble carbodiimide. Superhelical simian virus 40 (SV40) DNA I can be modified with N-cyclohexyl-N'-beta-(4 methylmorpholinium)ethylcarbodiimide (CMC). The reaction produces an increase in the sedimentation velocity of DNA I from 21 to 22.5S and a decrease in its buoyant density in CsCl from 1.694 to 1.688. A comparable shift in buoyant density is observed in a saturated ethidium bromide-cesium chloride gradient where form II, which has been exposed to CMC, shows no shift. The CsCl-buoyant density data allows us to estimate that 108 mol of CMC are bound per mol of SV40 DNA I. In the subsequent paper an alternative procedure has been used to locate CMC sites, and the extent of the regions available to bind CMC have been measured."} {"id": "PMID:176462", "title": "Hin D restriction mapping of upaired regions in simian virus 40 superhelical DNA I: considerations regarding structure-function relationships.", "content": "Superhelical simian virus 40 (SV40) DNA I was reacted with N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide (CMC), and the location of CMC sites was mapped using the Hin D restriction endonuclease. The use of 14C-labeled CMC allows a quantitative analysis of the binding to the respective Hin D restriction endonuclease fragments. The percentage of reactivity was 6.54% for fragment A, 3.87% for fragment B, and 2.74% for fragment G. No CMC radioactivity was detected in other fragments. This reactivity is in agreement with the evaluation of binding by buoyant density measurements. The above fragments also contain the sites susceptible to S1 endonuclease action. This adds further support to the view that superhelical DNA can contain regions of localized interrupted secondary structure which may be capable of forming intrastrand hairpin structures if sequence relationships are favorable. The possible structure-function relationships for this model are discussed with the emphasis on transcription.", "contents": "Hin D restriction mapping of upaired regions in simian virus 40 superhelical DNA I: considerations regarding structure-function relationships. Superhelical simian virus 40 (SV40) DNA I was reacted with N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide (CMC), and the location of CMC sites was mapped using the Hin D restriction endonuclease. The use of 14C-labeled CMC allows a quantitative analysis of the binding to the respective Hin D restriction endonuclease fragments. The percentage of reactivity was 6.54% for fragment A, 3.87% for fragment B, and 2.74% for fragment G. No CMC radioactivity was detected in other fragments. This reactivity is in agreement with the evaluation of binding by buoyant density measurements. The above fragments also contain the sites susceptible to S1 endonuclease action. This adds further support to the view that superhelical DNA can contain regions of localized interrupted secondary structure which may be capable of forming intrastrand hairpin structures if sequence relationships are favorable. The possible structure-function relationships for this model are discussed with the emphasis on transcription."} {"id": "PMID:176463", "title": "Structural and growth characteristics of infectious bursal disease virus.", "content": "The infectious bursal disease virus is not enveloped and has a diameter of 60 nm and a density of about 1.32 g/ml. It contains two pieces of single-stranded RNA with molecular weights close to 2 X 10(6). The capsid is made up of four major polypeptides with molecular weights of 110,000, 50,000, 35,000, and 25,000. The virus replicates in chicken embryo fibroblasts rather than in epitheloid cells. After an eclipse period of 4 h, virus production reaches a maximum about 12 h later. The virus has no structural or biological similarities with defined avian reoviruses, and it cannot be classified in one of the established taxonomic groups.", "contents": "Structural and growth characteristics of infectious bursal disease virus. The infectious bursal disease virus is not enveloped and has a diameter of 60 nm and a density of about 1.32 g/ml. It contains two pieces of single-stranded RNA with molecular weights close to 2 X 10(6). The capsid is made up of four major polypeptides with molecular weights of 110,000, 50,000, 35,000, and 25,000. The virus replicates in chicken embryo fibroblasts rather than in epitheloid cells. After an eclipse period of 4 h, virus production reaches a maximum about 12 h later. The virus has no structural or biological similarities with defined avian reoviruses, and it cannot be classified in one of the established taxonomic groups."} {"id": "PMID:176464", "title": "Blocked 5' termini in brome mosaic virus RNA.", "content": "All four components of brome mosaic virus RNA have m(7)G(5') ppp (5')Gp as their 5' terminus. The m(7)G can be removed by beta-elimination, resulting in the conversion to pppGp.", "contents": "Blocked 5' termini in brome mosaic virus RNA. All four components of brome mosaic virus RNA have m(7)G(5') ppp (5')Gp as their 5' terminus. The m(7)G can be removed by beta-elimination, resulting in the conversion to pppGp."} {"id": "PMID:176465", "title": "Proteins of Epstein-Barr Virus. II. Electrophoretic analysis of the polypeptides of the nucleocapsid and the glucosamine- and polysaccharide-containing components of enveloped virus.", "content": "Two series of experiments were undertaken to identify the topological location of the structural polypeptides of Epstein-Barr virus. In the first series of experiments, nucleocapsids prepared by detergent treatment of enveloped virus with Nonidet P-40 and sodium deoxycholate were found to be composed of seven polypeptides, VP2, 6, 7.5, 24, 27, 31, ANd 33, which ranged in molecular weight from over 200 X 10(3) to 28 X 10(3). Nine other polypeptides, VP 4, 7, 8, 10, 15, 16, 23, 28, and 29, could be identified in preparations of Epstein-Barr virus nucleocapsids, but the relative amount of this second group of polypeptides was less in preparations of nucleocapsids than in preparations of enveloped virus. The incomplete removal of these polypeptides from enveloped virus by detergent treatment suggests that some of these polypeptides may be components of the envelope or tegument that lie in close proximity to the outer surface of the nucleocapsid In the second series of experiments periodic acid-Schiff-staining and glucosamine-containing components were identified with similar electrophoretic mobility to several of the polypeptides of enveloped virus (VP 5, 8, 9, 11, 12, 13, 14, 15, 16, 17, 28, and 29) that were completely or incompletely removed from purified virus preparations by detergent treatment. The similarity between the polypeptide composition of the nucleocapsids of Epstein-Barr virus and herpes simplex virus was in contrast to the dissimilarity between the nonnucleocapsid polypeptides of Epstein-Barr virus and herpes simplex virus.", "contents": "Proteins of Epstein-Barr Virus. II. Electrophoretic analysis of the polypeptides of the nucleocapsid and the glucosamine- and polysaccharide-containing components of enveloped virus. Two series of experiments were undertaken to identify the topological location of the structural polypeptides of Epstein-Barr virus. In the first series of experiments, nucleocapsids prepared by detergent treatment of enveloped virus with Nonidet P-40 and sodium deoxycholate were found to be composed of seven polypeptides, VP2, 6, 7.5, 24, 27, 31, ANd 33, which ranged in molecular weight from over 200 X 10(3) to 28 X 10(3). Nine other polypeptides, VP 4, 7, 8, 10, 15, 16, 23, 28, and 29, could be identified in preparations of Epstein-Barr virus nucleocapsids, but the relative amount of this second group of polypeptides was less in preparations of nucleocapsids than in preparations of enveloped virus. The incomplete removal of these polypeptides from enveloped virus by detergent treatment suggests that some of these polypeptides may be components of the envelope or tegument that lie in close proximity to the outer surface of the nucleocapsid In the second series of experiments periodic acid-Schiff-staining and glucosamine-containing components were identified with similar electrophoretic mobility to several of the polypeptides of enveloped virus (VP 5, 8, 9, 11, 12, 13, 14, 15, 16, 17, 28, and 29) that were completely or incompletely removed from purified virus preparations by detergent treatment. The similarity between the polypeptide composition of the nucleocapsids of Epstein-Barr virus and herpes simplex virus was in contrast to the dissimilarity between the nonnucleocapsid polypeptides of Epstein-Barr virus and herpes simplex virus."} {"id": "PMID:176466", "title": "Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides.", "content": "Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.", "contents": "Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides. Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles."} {"id": "PMID:176467", "title": "N-Tropic variants obtained after co-infection with N- and B-tropic murine leukemia viruses.", "content": "Sc-1 cells co-infected with small XC plaque-forming N-tropic and large XC plaque-forming B-tropic murine leukemia viruses produced, in addition to parental types, progeny with the phenotype, large XC plaque morphology, and N-tropism. This phenotype remained stable through end point titration and plaque purification on NIH/3T3 cells and growth on BALB/3T3 cells. These N-tropic viruses (XLP-N virus) grow to unusually high titer and make very large XC plaques.", "contents": "N-Tropic variants obtained after co-infection with N- and B-tropic murine leukemia viruses. Sc-1 cells co-infected with small XC plaque-forming N-tropic and large XC plaque-forming B-tropic murine leukemia viruses produced, in addition to parental types, progeny with the phenotype, large XC plaque morphology, and N-tropism. This phenotype remained stable through end point titration and plaque purification on NIH/3T3 cells and growth on BALB/3T3 cells. These N-tropic viruses (XLP-N virus) grow to unusually high titer and make very large XC plaques."} {"id": "PMID:176468", "title": "Cooperative transformation studies with temperature-sensitive mutants of Rous sarcoma virus.", "content": "Stocks of Rous sarcoma virus Bryan strain were mutagenized using a bromodeoxyuridine treatment immediately after infection. Thirty temperature-sensitive (ts) mutants defective in transformation (td) were isolated by a replica plating technique. Twenty of these mutants were preliminarily characterized and found to be defective in late functions related to transformation. These mutants were used in experiments of cooperative transformation with four Prague strain td ts mutants of different co-transformation group. A small number of Bryan ts mutants were found to cooperate with some of the Prague mutants in transforming chicken embryo cells at the nonpermissive temperature. However, the amount of co-transformation observed was lower than that observed with cooperating Prague ts mutants and no clear-cut pattern of cotransformation was obtained in Prague and Bryan crosses. Indirect evidence indicates that cooperative transformation is the result of recombination events.", "contents": "Cooperative transformation studies with temperature-sensitive mutants of Rous sarcoma virus. Stocks of Rous sarcoma virus Bryan strain were mutagenized using a bromodeoxyuridine treatment immediately after infection. Thirty temperature-sensitive (ts) mutants defective in transformation (td) were isolated by a replica plating technique. Twenty of these mutants were preliminarily characterized and found to be defective in late functions related to transformation. These mutants were used in experiments of cooperative transformation with four Prague strain td ts mutants of different co-transformation group. A small number of Bryan ts mutants were found to cooperate with some of the Prague mutants in transforming chicken embryo cells at the nonpermissive temperature. However, the amount of co-transformation observed was lower than that observed with cooperating Prague ts mutants and no clear-cut pattern of cotransformation was obtained in Prague and Bryan crosses. Indirect evidence indicates that cooperative transformation is the result of recombination events."} {"id": "PMID:176469", "title": "Host restriction of Friend Leukemia virus coat protein synthesis.", "content": "Fv-1 gene-mediated host restriction of Friend leukemia virus replication was investigated in terms of coat protein synthesis. By using the assay of pseudotype formation with vesicular stomatitis virus. it was shown that under restricting growth conditions the availablity of leukemia virus coat protein for pseudotype formation was decreased. These studies appear to eliminate a pure assembly defect as the mechanism of Fv-1 host restriction.", "contents": "Host restriction of Friend Leukemia virus coat protein synthesis. Fv-1 gene-mediated host restriction of Friend leukemia virus replication was investigated in terms of coat protein synthesis. By using the assay of pseudotype formation with vesicular stomatitis virus. it was shown that under restricting growth conditions the availablity of leukemia virus coat protein for pseudotype formation was decreased. These studies appear to eliminate a pure assembly defect as the mechanism of Fv-1 host restriction."} {"id": "PMID:176470", "title": "Cell killing by simian virus 40: variation in the pattern of lysosomal enzyme release, cellular enzyme release, and cell death during productive infection of normal and simian virus 40-transformed simian cell lines.", "content": "Simian virus 40 (SV40) growth on rhesus kidney cells and on the T-22 line of SV40-transformed green monkey kidney (GMK) cells is largely limited by the low plating efficiency of SV40 on these cells. In addition, a fraction of the rhesus kidney and T-22 cells are resistant to infection by SV40. Nevertheless, 72-h viral yields per infected rhesus kidney and T-22 cell are nearly equivalent to that obtained on normal GMK cells and are independent of the multiplicity of infection. Despite the production of high viral yields, infected rhesus kidney and T-22 cells are killed slowly by SV40. Monolayers of these cells are also refractory to plaque formation by SV40. SV40 induces the release of lysosomal N-acetyl-beta-glucosaminidase into the cytoplasmic fractions of rhesus kidney and T-22 cells to an extent equal to that observed during infection of rapidly killed normal GMK cells. In contrast, damage to the plasma membrane, as indicated by the release of the cellular enzymes lactic dehydrogenase and glutamic oxaloacetic transaminase into the overlay media, occurred to a much greater extent in the normal GMK cells than in the rhesus kidney or T-22 cells. Neither a lysosomal hydrolase mechanism nor viral release appear to be responsible for this phenomenon. The different rates and extents of the SV40 cytocidal process on these cells do not result from the differences in the viral plating efficiency on them.", "contents": "Cell killing by simian virus 40: variation in the pattern of lysosomal enzyme release, cellular enzyme release, and cell death during productive infection of normal and simian virus 40-transformed simian cell lines. Simian virus 40 (SV40) growth on rhesus kidney cells and on the T-22 line of SV40-transformed green monkey kidney (GMK) cells is largely limited by the low plating efficiency of SV40 on these cells. In addition, a fraction of the rhesus kidney and T-22 cells are resistant to infection by SV40. Nevertheless, 72-h viral yields per infected rhesus kidney and T-22 cell are nearly equivalent to that obtained on normal GMK cells and are independent of the multiplicity of infection. Despite the production of high viral yields, infected rhesus kidney and T-22 cells are killed slowly by SV40. Monolayers of these cells are also refractory to plaque formation by SV40. SV40 induces the release of lysosomal N-acetyl-beta-glucosaminidase into the cytoplasmic fractions of rhesus kidney and T-22 cells to an extent equal to that observed during infection of rapidly killed normal GMK cells. In contrast, damage to the plasma membrane, as indicated by the release of the cellular enzymes lactic dehydrogenase and glutamic oxaloacetic transaminase into the overlay media, occurred to a much greater extent in the normal GMK cells than in the rhesus kidney or T-22 cells. Neither a lysosomal hydrolase mechanism nor viral release appear to be responsible for this phenomenon. The different rates and extents of the SV40 cytocidal process on these cells do not result from the differences in the viral plating efficiency on them."} {"id": "PMID:176471", "title": "Deoxyribonucleoside triphosphate pools in synchronized human cells infected with herpes simplex virus types 1 and 2.", "content": "Deoxyribonucleoside triphosphate pools in uninfected and herpes simplex virus type 1 (HSV-1)- and HSV-2-infected KB cells were analyzed to determine whether ribonucleotide reductase functions in vivo in the presence and absence of thymidine (TdR). Previously we showed that HSV-2 replication was inhibited in KB cells blocked in their capacity to synthesize DNA by TdR. HSV-1 replication was not inhibited under these conditions. Both HSV-1 and HSV-2 induced an altered ribonucleotide reductase resistant to dTTP inhibition. Thus, the block to HSV-2 replication apparently was not at the level of reductase. However, the in vitro activity of the enzyme does not necessarily correspond to intracellular conditions. In TdR-blocked HSV-2-infected cells, we found that, while dTTP levels remained high, dCTP concentrations increased. In contrast, KB cells blocked by TdR showed increased dTTP but decreased dCTP levels. We conclude that the HSV-2 enzyme is functional in vivo and that TdR inhibits viral replication by a mechanism other than depletion of dCTP. Infection of KB cells with HSV-1 or HSV-2 altered both dATP and dGTP levels in the presence or absence of TdR. Inhibition of viral replication was not explained by changes in these pools. We suggest that, during infection, HSV-1 induces a virus function(s) not related to reductase which is resistant to TdR, whereas the corresponding HSV-2 function is sensitive. Our evidence shows that the TdR-sensitive function is not in the pathways leading to deoxyribonucleoside triphosphate and may occur at the level of DNA replication.", "contents": "Deoxyribonucleoside triphosphate pools in synchronized human cells infected with herpes simplex virus types 1 and 2. Deoxyribonucleoside triphosphate pools in uninfected and herpes simplex virus type 1 (HSV-1)- and HSV-2-infected KB cells were analyzed to determine whether ribonucleotide reductase functions in vivo in the presence and absence of thymidine (TdR). Previously we showed that HSV-2 replication was inhibited in KB cells blocked in their capacity to synthesize DNA by TdR. HSV-1 replication was not inhibited under these conditions. Both HSV-1 and HSV-2 induced an altered ribonucleotide reductase resistant to dTTP inhibition. Thus, the block to HSV-2 replication apparently was not at the level of reductase. However, the in vitro activity of the enzyme does not necessarily correspond to intracellular conditions. In TdR-blocked HSV-2-infected cells, we found that, while dTTP levels remained high, dCTP concentrations increased. In contrast, KB cells blocked by TdR showed increased dTTP but decreased dCTP levels. We conclude that the HSV-2 enzyme is functional in vivo and that TdR inhibits viral replication by a mechanism other than depletion of dCTP. Infection of KB cells with HSV-1 or HSV-2 altered both dATP and dGTP levels in the presence or absence of TdR. Inhibition of viral replication was not explained by changes in these pools. We suggest that, during infection, HSV-1 induces a virus function(s) not related to reductase which is resistant to TdR, whereas the corresponding HSV-2 function is sensitive. Our evidence shows that the TdR-sensitive function is not in the pathways leading to deoxyribonucleoside triphosphate and may occur at the level of DNA replication."} {"id": "PMID:176472", "title": "Early events after infection of Escherichia coli by bacteriophage T5. II. Control of the bacteriophage-induced 5'-nucleotidase activity.", "content": "The control of activity of the bacteriophage T5-induced 5'-nucleotidase is dependent upon the amount of T5 parental DNA injected into the cell and expressed. When only the first-step transfer DNA is injected and expressed the amount of 5'-nucleotidase activity observed is two to three times the maximum amount observed after normal T5 infection, and inactivation of the enzyme does not occur. Enzyme inactivation occurs only after the remaining DNA is injected, but only limited expression of this DNA is required. The control of the nucleotidase inactivation process is similar to that for the repair of the nicks in parental DNA, and is probably mediated by a class IIa protein.", "contents": "Early events after infection of Escherichia coli by bacteriophage T5. II. Control of the bacteriophage-induced 5'-nucleotidase activity. The control of activity of the bacteriophage T5-induced 5'-nucleotidase is dependent upon the amount of T5 parental DNA injected into the cell and expressed. When only the first-step transfer DNA is injected and expressed the amount of 5'-nucleotidase activity observed is two to three times the maximum amount observed after normal T5 infection, and inactivation of the enzyme does not occur. Enzyme inactivation occurs only after the remaining DNA is injected, but only limited expression of this DNA is required. The control of the nucleotidase inactivation process is similar to that for the repair of the nicks in parental DNA, and is probably mediated by a class IIa protein."} {"id": "PMID:176474", "title": "Antigenic activity of human urothelial tissue.", "content": "Partially purified extracts from 71 human urothelial tumors and from 75 human urothelial non-tumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of 1 of the structural components of type C-ribonucleic and viruses, the p30 core protein. Testing of the tissue extracts was carried out by homologous and heterologous assay systems using 125I-labeled murine (Friend) and feline (Rickard) p30 antigens and anti-feline and anti-murine p30 antisera. The homologous assays were designed to detect the presence of p30 antigens in the human tissue extracts having similar characteristics to the p30 antigens of either the feline or murine type C viruses. The heterologous assay system was designed to detect interspecies antigenic determinants common to murine and feline viruses and also primate viruses. A competing antigen present in 28 per cent of the tissue extracts assayed demonstrated an antigenic protein that competed with the viral p30 protein used in the heterologous radioimmunoassay system and to a lesser extent in the homologous feline radioimmunoassay system. Antigenic competitor proteins were found in tumor and non-tumor tissue. These data suggest that some human urothelial tissues contain at least part of the genome of 1 or more type C viruses. Those tissues that are positive only in the heterologous assay system behave like viral p30 antigens already identified in tissues of several other primates. Those tissues that are positive in the heterologous assay system and the homologous system indicate that the p30 antigenic activity is closely related to that p30 present in feline C-type viruses. Further purification and more detailed characterization of those competing proteins are now under study.", "contents": "Antigenic activity of human urothelial tissue. Partially purified extracts from 71 human urothelial tumors and from 75 human urothelial non-tumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of 1 of the structural components of type C-ribonucleic and viruses, the p30 core protein. Testing of the tissue extracts was carried out by homologous and heterologous assay systems using 125I-labeled murine (Friend) and feline (Rickard) p30 antigens and anti-feline and anti-murine p30 antisera. The homologous assays were designed to detect the presence of p30 antigens in the human tissue extracts having similar characteristics to the p30 antigens of either the feline or murine type C viruses. The heterologous assay system was designed to detect interspecies antigenic determinants common to murine and feline viruses and also primate viruses. A competing antigen present in 28 per cent of the tissue extracts assayed demonstrated an antigenic protein that competed with the viral p30 protein used in the heterologous radioimmunoassay system and to a lesser extent in the homologous feline radioimmunoassay system. Antigenic competitor proteins were found in tumor and non-tumor tissue. These data suggest that some human urothelial tissues contain at least part of the genome of 1 or more type C viruses. Those tissues that are positive only in the heterologous assay system behave like viral p30 antigens already identified in tissues of several other primates. Those tissues that are positive in the heterologous assay system and the homologous system indicate that the p30 antigenic activity is closely related to that p30 present in feline C-type viruses. Further purification and more detailed characterization of those competing proteins are now under study."} {"id": "PMID:176473", "title": "Host range temperature-sensitive mutants of herpes simplex virus type 2.", "content": "Two small-plaque mutants of herpes simplex virus type 2 (HSV-2) (strain 333), whose growth at 39 C was blocked in certain cell types (cell-dependent temperature sensitivity), were compared compared with parental virus in a number of biological assays. One mutant (no. 69) was found to produce a large number of morphologically normal, but noninfectious, particles; under nonpermissive conditions, these mutant particles were able to interfere with the replication of wild-type HSV-2. The other mutant (no. 74), which is known to belong to a different complementation group, appeared to direct little virus DNA synthesis, even at the permissive temperature. Progeny production and virus DNA synthesis in cells infected by mutant 74 were delayed in comparison with wild-type virus-infected cells. Both mutants were found to be more sensitive to UV irradiation than the parental virus; this was especially marked in the case of mutant 74. Moreover, this mutant was found to have a high transforming efficiency at much lower doses of irradiation than those needed to abolish the cytopathic effect of wildtype HSV-2.", "contents": "Host range temperature-sensitive mutants of herpes simplex virus type 2. Two small-plaque mutants of herpes simplex virus type 2 (HSV-2) (strain 333), whose growth at 39 C was blocked in certain cell types (cell-dependent temperature sensitivity), were compared compared with parental virus in a number of biological assays. One mutant (no. 69) was found to produce a large number of morphologically normal, but noninfectious, particles; under nonpermissive conditions, these mutant particles were able to interfere with the replication of wild-type HSV-2. The other mutant (no. 74), which is known to belong to a different complementation group, appeared to direct little virus DNA synthesis, even at the permissive temperature. Progeny production and virus DNA synthesis in cells infected by mutant 74 were delayed in comparison with wild-type virus-infected cells. Both mutants were found to be more sensitive to UV irradiation than the parental virus; this was especially marked in the case of mutant 74. Moreover, this mutant was found to have a high transforming efficiency at much lower doses of irradiation than those needed to abolish the cytopathic effect of wildtype HSV-2."} {"id": "PMID:176475", "title": "Renal cyst puncture: a non-diagnostic procedure in the infant.", "content": "A case of metastatic Wilms tumor in a newborn is presented. Cyst puncture was included in the preoperative evaluation and the merits of this procedure in infants are questioned. The differential diagnosis of intrarenal masses in the neonate is discussed.", "contents": "Renal cyst puncture: a non-diagnostic procedure in the infant. A case of metastatic Wilms tumor in a newborn is presented. Cyst puncture was included in the preoperative evaluation and the merits of this procedure in infants are questioned. The differential diagnosis of intrarenal masses in the neonate is discussed."} {"id": "PMID:176477", "title": "The prevalence of antibody to infectious bovine rhinotracheitis virus in some game animals of East Africa.", "content": "Antibody to infectious bovine rhinotracheitis virus was present in the sera of 10 of 25 species of game animals from Kenya, Tanzania and Uganda during 1960-1973. Prevalence of antibody varied considerably between, but not within, species.", "contents": "The prevalence of antibody to infectious bovine rhinotracheitis virus in some game animals of East Africa. Antibody to infectious bovine rhinotracheitis virus was present in the sera of 10 of 25 species of game animals from Kenya, Tanzania and Uganda during 1960-1973. Prevalence of antibody varied considerably between, but not within, species."} {"id": "PMID:176478", "title": "An epornitic of duck plague on a Wisconsin game farm.", "content": "In April, 1973, an acute disease with a high rate of mortality appeared in a flock of 233 ducks and geese at a private game farm. Most of the flock (220) were black ducks (Anas rubripes) and mortality was restricted to them. In May, the remaining live birds were placed in isolation but mortality continued in black ducks and occurred in other species. The overall rate of mortality for black ducks was 93% and the case fatality rate was 97%. No hemorrhaging from either the bill or vent was observed. The most commonly observed gross lesions were extensive fibrino-necrotic plaques covering the mucosal surface of the esophagus, posterior colon and cloaca. Petechial and ecchymotic hemorrhages on visceral organs, particularly the heart, were also common. Virus isolation was attempted from tissues of three black ducks. Duck plague virus was isolated from liver, kidney, spleen and intestine of each. Sixteen black ducks survived the outbreak. Seven of these birds had significant levels of neutralizing antibody to duck plague virus.", "contents": "An epornitic of duck plague on a Wisconsin game farm. In April, 1973, an acute disease with a high rate of mortality appeared in a flock of 233 ducks and geese at a private game farm. Most of the flock (220) were black ducks (Anas rubripes) and mortality was restricted to them. In May, the remaining live birds were placed in isolation but mortality continued in black ducks and occurred in other species. The overall rate of mortality for black ducks was 93% and the case fatality rate was 97%. No hemorrhaging from either the bill or vent was observed. The most commonly observed gross lesions were extensive fibrino-necrotic plaques covering the mucosal surface of the esophagus, posterior colon and cloaca. Petechial and ecchymotic hemorrhages on visceral organs, particularly the heart, were also common. Virus isolation was attempted from tissues of three black ducks. Duck plague virus was isolated from liver, kidney, spleen and intestine of each. Sixteen black ducks survived the outbreak. Seven of these birds had significant levels of neutralizing antibody to duck plague virus."} {"id": "PMID:176479", "title": "MBK neuropathy among spray painters.", "content": "It has been suggested that the solvent methyl N-butyl ketone (MBK) may cause peripheral neuropathy in humans. An investigation was undertaken after two cases of peripheral neuropathy among spray painters at one work site were reported to the National Institute for Occupational Safety and Health. Twenty-six painters were interviewed and examined. Two were found to have definite peripheral neuropathy and one had a probable case. Although one of these men had been exposed to lead in the past, there are strong reasons to believe that MBK was responsible for his neuropathy. There was nothing to suggest excessive lead absorption in the other two men.", "contents": "MBK neuropathy among spray painters. It has been suggested that the solvent methyl N-butyl ketone (MBK) may cause peripheral neuropathy in humans. An investigation was undertaken after two cases of peripheral neuropathy among spray painters at one work site were reported to the National Institute for Occupational Safety and Health. Twenty-six painters were interviewed and examined. Two were found to have definite peripheral neuropathy and one had a probable case. Although one of these men had been exposed to lead in the past, there are strong reasons to believe that MBK was responsible for his neuropathy. There was nothing to suggest excessive lead absorption in the other two men."} {"id": "PMID:176480", "title": "Superior vena caval obstruction due to small-cell anaplastic lung carcinoma. Response to chemotherapy.", "content": "Among 38 patients with bronchogenic carcinoma, small-cell type, eight patients had superior vena caval obstruction (SVCO) of recent onset. Seven of these patients were initially treated with combination chemotherapy (lomustine, cyclophosphamide, and methotrexate). One patient who had SVCO was treated initially by radiotherapy, with subsequent chemotherapy. In each patient, resolution of the syndrome was prompt, usually was complete by seven days, and was accompanied by objective tumor shrinkage. Symptoms of SVCO were transiently aggravated by the initiation of treatment in only one patient. In one individual treated by chemotherapy alone and in one treated by chemotherapy plus radiotherapy, SVCO recurred after initial control. Chemotherapy is an effective form of management of SVCO caused by small-cell carcinoma of the lung.", "contents": "Superior vena caval obstruction due to small-cell anaplastic lung carcinoma. Response to chemotherapy. Among 38 patients with bronchogenic carcinoma, small-cell type, eight patients had superior vena caval obstruction (SVCO) of recent onset. Seven of these patients were initially treated with combination chemotherapy (lomustine, cyclophosphamide, and methotrexate). One patient who had SVCO was treated initially by radiotherapy, with subsequent chemotherapy. In each patient, resolution of the syndrome was prompt, usually was complete by seven days, and was accompanied by objective tumor shrinkage. Symptoms of SVCO were transiently aggravated by the initiation of treatment in only one patient. In one individual treated by chemotherapy alone and in one treated by chemotherapy plus radiotherapy, SVCO recurred after initial control. Chemotherapy is an effective form of management of SVCO caused by small-cell carcinoma of the lung."} {"id": "PMID:176481", "title": "Orphan airlift. Enteric pathogens isolated from Vietnamese children immigrating to the United States.", "content": "Isolation studies for bacterial and parasitic agents were carried out on stool specimens from Vietnamese infants at the time of their mass airlift to the United States. One or more bacterial pathogens were found in 49% of the 367 stool specimens cultured. The isolates included enteropathogenic Escherichia coli (161), Shigella (16), Salmonella (15), but no Salmonella typhi or Vibrio cholerae. Parasites identified in 88 stool specimens included Giardia lamblia (10), Ascaris lumbricoides (7), and Entamoeba histolytica (1). Transmission of agents to volunteers probably occurred, because 48% of 272 adults questioned had diarrhea shortly after caring for the children, and stool cultures from these adults resulted in the isolation of E coli (105), Salmonella (1), and Shigella (3).", "contents": "Orphan airlift. Enteric pathogens isolated from Vietnamese children immigrating to the United States. Isolation studies for bacterial and parasitic agents were carried out on stool specimens from Vietnamese infants at the time of their mass airlift to the United States. One or more bacterial pathogens were found in 49% of the 367 stool specimens cultured. The isolates included enteropathogenic Escherichia coli (161), Shigella (16), Salmonella (15), but no Salmonella typhi or Vibrio cholerae. Parasites identified in 88 stool specimens included Giardia lamblia (10), Ascaris lumbricoides (7), and Entamoeba histolytica (1). Transmission of agents to volunteers probably occurred, because 48% of 272 adults questioned had diarrhea shortly after caring for the children, and stool cultures from these adults resulted in the isolation of E coli (105), Salmonella (1), and Shigella (3)."} {"id": "PMID:176493", "title": "The regulation of respiration of guinea pig taenia coli in high-K medium: the role of nicotinamide-adenine dinucleotide, adenosine diphosphate and Ca++.", "content": "In an attempt to elucidate the regulation mechanism of respiration in the smooth muscle cell, we investigated the roles of nicotinamide-adenine dinucleotide (NAD), adenosine diphosphate (ADP) and Ca++ in the muscle respiration using the tissues and subcellular fractions from guinea pig taenia coli. The tension in the strips of taenia coli increased with a concomitant increase in O2 consumption in high-K medium (40 mM K) containing 2.5 mM Ca. 10(-3) M amytal and 10(-5)M ouabain decreased the high-K induced tension and O2 consumption of the muscle. 10(-4)M 2,4-dinitrophenol (DNP) relieved the decreased respiration induced by ouabain, but not that with amytal. From these data it is suggested that NADH-linked respiration plays an important role in the respiration of the muscle. Ca++ in concentrations ranging from 0.5 to 2.5 mM in the high-K medium resulted in an increase in tension and in O2 concumption progressively. In spectrophotometric observations of subcellular fractions of the taenia coli, ADP increased in absorbance change at 340 m mu. Such occurred in mitochondrial fractions and was initiated by the addition of NADH. Therefore it is deduced that the increase in ADP level of the cytoplasm is primarily due to a contraction triggered by Ca++ thus stimulating respiration. On the other hand, at 0.1 mM of Ca++ concentration, the muscle strip increased O2 consumption without tension development in high-K medium. In the spectrophotometric observations, Ca++ and Sr++ increased the absorbance change in the homogenate and in the mitochondrial fraction. Hence, it seems that one part of the Ca++ entering into the smooth muscle treated with the high-K increased O2 consumption in mitochondia independent of an increase in muscle tension. From these results it is concluded that NADH-linked respiration plays an important role in the smooth muscle respiration in high-K medium and that ADP and Ca++ also play a role in regulating respiration.", "contents": "The regulation of respiration of guinea pig taenia coli in high-K medium: the role of nicotinamide-adenine dinucleotide, adenosine diphosphate and Ca++. In an attempt to elucidate the regulation mechanism of respiration in the smooth muscle cell, we investigated the roles of nicotinamide-adenine dinucleotide (NAD), adenosine diphosphate (ADP) and Ca++ in the muscle respiration using the tissues and subcellular fractions from guinea pig taenia coli. The tension in the strips of taenia coli increased with a concomitant increase in O2 consumption in high-K medium (40 mM K) containing 2.5 mM Ca. 10(-3) M amytal and 10(-5)M ouabain decreased the high-K induced tension and O2 consumption of the muscle. 10(-4)M 2,4-dinitrophenol (DNP) relieved the decreased respiration induced by ouabain, but not that with amytal. From these data it is suggested that NADH-linked respiration plays an important role in the respiration of the muscle. Ca++ in concentrations ranging from 0.5 to 2.5 mM in the high-K medium resulted in an increase in tension and in O2 concumption progressively. In spectrophotometric observations of subcellular fractions of the taenia coli, ADP increased in absorbance change at 340 m mu. Such occurred in mitochondrial fractions and was initiated by the addition of NADH. Therefore it is deduced that the increase in ADP level of the cytoplasm is primarily due to a contraction triggered by Ca++ thus stimulating respiration. On the other hand, at 0.1 mM of Ca++ concentration, the muscle strip increased O2 consumption without tension development in high-K medium. In the spectrophotometric observations, Ca++ and Sr++ increased the absorbance change in the homogenate and in the mitochondrial fraction. Hence, it seems that one part of the Ca++ entering into the smooth muscle treated with the high-K increased O2 consumption in mitochondia independent of an increase in muscle tension. From these results it is concluded that NADH-linked respiration plays an important role in the smooth muscle respiration in high-K medium and that ADP and Ca++ also play a role in regulating respiration."} {"id": "PMID:176501", "title": "[\"Hypo-alpha-lipoproteinemia\" (Tangier-disease) (author's transl)].", "content": "Report on a case of Tangier disease in a girl aged 4.11 m. Clinically the tonsils were hypertrophic and of a yellow color. Their stroma contained many cholesterinesters which produced the histologic picture of foam-cell xanthomatosis. The serum contained only traces of alpha-lipoprotein. The level of Cholesterin of the HDL fraction was reduced to one twelvth of the norm. The serum of her father also showed a clearly reduced content of HDL cholesterin. In the patient herself lipolytic enzymes like lecithin-cholesterin-acyltransferase, post-heparin plasma-lipoprotein lipase and hepatic triglycerid-lipase showed normal activity.", "contents": "[\"Hypo-alpha-lipoproteinemia\" (Tangier-disease) (author's transl)]. Report on a case of Tangier disease in a girl aged 4.11 m. Clinically the tonsils were hypertrophic and of a yellow color. Their stroma contained many cholesterinesters which produced the histologic picture of foam-cell xanthomatosis. The serum contained only traces of alpha-lipoprotein. The level of Cholesterin of the HDL fraction was reduced to one twelvth of the norm. The serum of her father also showed a clearly reduced content of HDL cholesterin. In the patient herself lipolytic enzymes like lecithin-cholesterin-acyltransferase, post-heparin plasma-lipoprotein lipase and hepatic triglycerid-lipase showed normal activity."} {"id": "PMID:176502", "title": "[Granulocyte dysfunction. I. Inborn defects (author's transl)].", "content": "The insight in the function and dysfunction of granulocytes lately arouses more and more interest. This report summarises our present knowledge. In the first of two chapters the authors review the molecular basis of granulocyte function and the inborn defects of chemotaxis, opsonisation, phagocytosis and intracellular killing of bacteria and fungi.", "contents": "[Granulocyte dysfunction. I. Inborn defects (author's transl)]. The insight in the function and dysfunction of granulocytes lately arouses more and more interest. This report summarises our present knowledge. In the first of two chapters the authors review the molecular basis of granulocyte function and the inborn defects of chemotaxis, opsonisation, phagocytosis and intracellular killing of bacteria and fungi."} {"id": "PMID:176503", "title": "[Diurnal profiles of plasma aldosterone, cortisol, renin, angiotensinogen and angiotensinases in normal subjects (author's transl)].", "content": "Plasma cortisol and renin were estimated in 1 h intervals, plasma aldosterone, angiotensinogen and angiotensinases in 3 h intervals over periods of 24 h in six normal volunteers (age 20-26) under control conditions and subsequently under suppression of ACTH release by dexamethasone. Highest cortisol levels were found around 7 a.m., minimum levels between 9 p.m. and 1 a.m. Dexamethasone reduced cortisol to constantly low concentrations. Aldosterone was highest around 4 a.m. under control conditions and under dexamethasone, and showed lowest concentrations between 4 and 10 p.m. There were no significant differences between mean aldosterone concentrations at corresponding time points of the control and the dexamethasone period. Similar to aldosterone, renen showed peak values around 4 a.m. All mean values at corresponding time points between 7 a.m. and 11 p.m. and the 24 hour mean values of each subject were significantly increased under the influence of dexamethasone. No evidence could be achieved for the existence of circadian rhythms of angiotensinogen and angiotensinases. Dexamethasone did not cause significant changes of these parameters.", "contents": "[Diurnal profiles of plasma aldosterone, cortisol, renin, angiotensinogen and angiotensinases in normal subjects (author's transl)]. Plasma cortisol and renin were estimated in 1 h intervals, plasma aldosterone, angiotensinogen and angiotensinases in 3 h intervals over periods of 24 h in six normal volunteers (age 20-26) under control conditions and subsequently under suppression of ACTH release by dexamethasone. Highest cortisol levels were found around 7 a.m., minimum levels between 9 p.m. and 1 a.m. Dexamethasone reduced cortisol to constantly low concentrations. Aldosterone was highest around 4 a.m. under control conditions and under dexamethasone, and showed lowest concentrations between 4 and 10 p.m. There were no significant differences between mean aldosterone concentrations at corresponding time points of the control and the dexamethasone period. Similar to aldosterone, renen showed peak values around 4 a.m. All mean values at corresponding time points between 7 a.m. and 11 p.m. and the 24 hour mean values of each subject were significantly increased under the influence of dexamethasone. No evidence could be achieved for the existence of circadian rhythms of angiotensinogen and angiotensinases. Dexamethasone did not cause significant changes of these parameters."} {"id": "PMID:176504", "title": "[Post-heparin-lipolytic activity in acute ethanol-induced hyperlipoproteinemia (author's transl)].", "content": "Post-heparin lipolytic-activity (PHLA) was studied in 10 healthy volunteers ingesting 0.5 g of ethanol/kg body weight initially and 0.1 g/kg body weight and hour over 5 hours. This dose led to enhancement in plasma triglycerides to about 170% of the pre-ethanol values. PHLA was determined before, 15 min, 1 and 5 hours after intake of the initial dose and showed no significant changes. These findings are compared with the results of earlier investigations. It is concluded that acute ethanol induced hyperlipoproteinemia in healthy man seems to be due mainly to enhanced hepatic synthesis of triglycerides and release of very low density lipoproteins and not to decrease catabolism of triglyceride rich lipoproteins.", "contents": "[Post-heparin-lipolytic activity in acute ethanol-induced hyperlipoproteinemia (author's transl)]. Post-heparin lipolytic-activity (PHLA) was studied in 10 healthy volunteers ingesting 0.5 g of ethanol/kg body weight initially and 0.1 g/kg body weight and hour over 5 hours. This dose led to enhancement in plasma triglycerides to about 170% of the pre-ethanol values. PHLA was determined before, 15 min, 1 and 5 hours after intake of the initial dose and showed no significant changes. These findings are compared with the results of earlier investigations. It is concluded that acute ethanol induced hyperlipoproteinemia in healthy man seems to be due mainly to enhanced hepatic synthesis of triglycerides and release of very low density lipoproteins and not to decrease catabolism of triglyceride rich lipoproteins."} {"id": "PMID:176505", "title": "Defects in granulocyte function in various chromosome abnormalities (Down's-, Edwards'-, Cri-du-chat syndrome).", "content": "In five infants with autosomal aberrations and diminished resistance to infection (in spite of intact humoral and cellular immune mechanisms) several granulocyte functions (chemotaxis, phagocytosis, intracellular killing and metabolism of killing) were measured. A serum-dependent or a cell-dependent disturbance of phagocytosis of Candida albicans was found in two infants with cat-cry syndrome and one with trisomy 18. In one of these children there was an additional serum dependent defect of the killing of Candida albicans and of Staphylococcus aureus, serum levels of opsonins (IgG, IgM, CH50 and C3) being within normal range. An infant with trisomy 21 showed, in addition to a cellular defect of chemotaxis, a reduced cellular ability of the killing of Staphylococcus aureus and of Escherichia coli in autologous and AB-pool-serum. Phagocytosis of these bacteria remained normal.", "contents": "Defects in granulocyte function in various chromosome abnormalities (Down's-, Edwards'-, Cri-du-chat syndrome). In five infants with autosomal aberrations and diminished resistance to infection (in spite of intact humoral and cellular immune mechanisms) several granulocyte functions (chemotaxis, phagocytosis, intracellular killing and metabolism of killing) were measured. A serum-dependent or a cell-dependent disturbance of phagocytosis of Candida albicans was found in two infants with cat-cry syndrome and one with trisomy 18. In one of these children there was an additional serum dependent defect of the killing of Candida albicans and of Staphylococcus aureus, serum levels of opsonins (IgG, IgM, CH50 and C3) being within normal range. An infant with trisomy 21 showed, in addition to a cellular defect of chemotaxis, a reduced cellular ability of the killing of Staphylococcus aureus and of Escherichia coli in autologous and AB-pool-serum. Phagocytosis of these bacteria remained normal."} {"id": "PMID:176534", "title": "The effect of transformation-defective avian oncornavirus mutants on tumor antigen expression.", "content": "The recent isolation of conditional (temperature sensitive) and nonconditional transformation-defective mutants of avian sarcoma virus strains has facilitated the investigation of the effect of virus transformation on the cell's phenotype, e.g., with respect to morphology, growth pattern, or cell surface antigenicity. Special emphasis was laid on elucidating the correlation between transformed phenotype and tumor antigen expression. All of the tested nontransforming deletion mutants and the majority of the temperature-sensitive mutants were unable to induce tumor antigens in phenotypically untransformed cells. However, 3 temperature-sensitive mutants were found which were able to support the expression of tumor specific surface antigens even at restrictive temperature, when cells otherwise exhibited a normal phenotype. The theoretical and practical implications of this association between normal phenotype and tumor antigen expression are discussed.", "contents": "The effect of transformation-defective avian oncornavirus mutants on tumor antigen expression. The recent isolation of conditional (temperature sensitive) and nonconditional transformation-defective mutants of avian sarcoma virus strains has facilitated the investigation of the effect of virus transformation on the cell's phenotype, e.g., with respect to morphology, growth pattern, or cell surface antigenicity. Special emphasis was laid on elucidating the correlation between transformed phenotype and tumor antigen expression. All of the tested nontransforming deletion mutants and the majority of the temperature-sensitive mutants were unable to induce tumor antigens in phenotypically untransformed cells. However, 3 temperature-sensitive mutants were found which were able to support the expression of tumor specific surface antigens even at restrictive temperature, when cells otherwise exhibited a normal phenotype. The theoretical and practical implications of this association between normal phenotype and tumor antigen expression are discussed."} {"id": "PMID:176535", "title": "Nonrandom distribution of receptors for melanocyte-stimulating hormone on the surface of mouse melanoma cells.", "content": "An improved bubble method was developed for applying an ultrathin layer of nuclear track emulsion on the surface of cells labeled with I125-MSH. The autoradiographs of I125-MSH binding indicate a nonrandom distribution of receptors on the surface of mouse melanoma cells. It is suggested that MSH receptors are displayed in clusters previous to and independently of their exposure to the hormone.", "contents": "Nonrandom distribution of receptors for melanocyte-stimulating hormone on the surface of mouse melanoma cells. An improved bubble method was developed for applying an ultrathin layer of nuclear track emulsion on the surface of cells labeled with I125-MSH. The autoradiographs of I125-MSH binding indicate a nonrandom distribution of receptors on the surface of mouse melanoma cells. It is suggested that MSH receptors are displayed in clusters previous to and independently of their exposure to the hormone."} {"id": "PMID:176536", "title": "Chromosomally depleted interspecific hybrid cell clones selected with cytotoxic antisera: utilization in the study of control of murine leukemia virus host-range.", "content": "A chromosomally stable mouse-Chinese hamster hybrid cell line was subjected to five rounds of selection with cytotoxic antisera raised in rabbits against either the parental mouse 3T3 cells or the parental Chinese hamster Wg-1 cells. Routine karyological analysis of clones isolated at each stage of serum selection revealed that treatment with either serum resulted in a limited loss of chromosomes (compared to the untreated hybrid cell cultured in parallel) and that the pattern of chromosome loss could not be correlated with the particular antiserum used for selection. However, more detailed analysis with the SSC-formamide C-banding technique, which identifies chromosomes containing a mouse centromere region, demonstrated that while large-scale chromosome loss was not achieved as a result of antiserum selection, the limited loss of chromosomes did, in fact, reflect a specific depletion of chromosomes in response to treatment with cytotoxic antiserum. Specific chromosomal elimination was shown to occur as early as the first round of antiserum treatment. Antigenic analysis of the serum-selected clones revealed a quantitative decrease in the expression of the species-specific surface antigens selected against, but no qualitative loss of antigens was detected. The results suggest that treatment with cytotoxic antiserum may select for clones that have lost specific chromosomes bearing genes regulating the expression of species-specific surface antigens, rather than for those demonstrating large-scale depletion of chromosomes bearing the corresponding structural genes. Some of these chromosomally depleted hybrid cell clones have been used (along with pseudotype viruses containing the genome of vesicular stomatitis virus within the envelope of murine leukemia virus, VSV [MuLV]), to study the mechanisms regulating MuLV replication in Chinese hamster cells. The results indicate that the restriction of MuLV replication in Chinese hamster cells operates at two levels: (a) an inability to adsorb to or penetrate Chinese hamster cells; and (b) an additional intracellular block which is dominant in the mouse-Chinese hamster hybrid cell clones examined. This latter block is presently under study.", "contents": "Chromosomally depleted interspecific hybrid cell clones selected with cytotoxic antisera: utilization in the study of control of murine leukemia virus host-range. A chromosomally stable mouse-Chinese hamster hybrid cell line was subjected to five rounds of selection with cytotoxic antisera raised in rabbits against either the parental mouse 3T3 cells or the parental Chinese hamster Wg-1 cells. Routine karyological analysis of clones isolated at each stage of serum selection revealed that treatment with either serum resulted in a limited loss of chromosomes (compared to the untreated hybrid cell cultured in parallel) and that the pattern of chromosome loss could not be correlated with the particular antiserum used for selection. However, more detailed analysis with the SSC-formamide C-banding technique, which identifies chromosomes containing a mouse centromere region, demonstrated that while large-scale chromosome loss was not achieved as a result of antiserum selection, the limited loss of chromosomes did, in fact, reflect a specific depletion of chromosomes in response to treatment with cytotoxic antiserum. Specific chromosomal elimination was shown to occur as early as the first round of antiserum treatment. Antigenic analysis of the serum-selected clones revealed a quantitative decrease in the expression of the species-specific surface antigens selected against, but no qualitative loss of antigens was detected. The results suggest that treatment with cytotoxic antiserum may select for clones that have lost specific chromosomes bearing genes regulating the expression of species-specific surface antigens, rather than for those demonstrating large-scale depletion of chromosomes bearing the corresponding structural genes. Some of these chromosomally depleted hybrid cell clones have been used (along with pseudotype viruses containing the genome of vesicular stomatitis virus within the envelope of murine leukemia virus, VSV [MuLV]), to study the mechanisms regulating MuLV replication in Chinese hamster cells. The results indicate that the restriction of MuLV replication in Chinese hamster cells operates at two levels: (a) an inability to adsorb to or penetrate Chinese hamster cells; and (b) an additional intracellular block which is dominant in the mouse-Chinese hamster hybrid cell clones examined. This latter block is presently under study."} {"id": "PMID:176537", "title": "Structure and function of cholera toxin and hormone receptors.", "content": "The enterotoxin from Vibrio cholerae is a protein of 100,000 mol wt which stimulates adenylate cyclase activity ubiquitously. The binding of biologically active 125I-labeled choleragen to cell membranes is of extraordinary affinity and specificity. The binding may be restricted to membrane-bound ganglioside GM1. This ganglioside can be inserted into membranes from exogenous sources, and the increased toxin binding in such cells can be reflected by an increased sensitivity to the biological effects of the toxin. Features of the toxin-activated adenylate cyclase, including conversion of the enzyne to a GTP-sensitive state, and the increased sensitivity of activation by hormones, suggest analogies between the basic mechanism of action of choleragen and the events following binding of hormones to their receptors. The action of the toxin is probably not mediated through intermediary cytoplasmic events, suggesting that its effects are entirely due to processes involving the plasma membrane. The kinetics of activation of adenylate cyclase in erythrocytes from various species as well as in rat adipocytes suggest a direct interaction between toxin and the cyclase enzyme which is difficult to reconcile with catalytic mechanisms of adenylate cyclase activation. Direct evidence for this can be obtained from the comigration of toxin radioactivity with adenylate cyclase activity when toxin-activated membranes are dissolved in detergents and chromatographed on gel filtration columns. Agarose derivatives containing the \"active\" subunit of the toxin can specifically absorb adenylate cyclase activity, and specific antibodies against the choleragen can be used for selective immunoprecipitation of adenylate cyclase activity from detergent-solubilized preparations of activated membranes. It is proposed that toxin action involves the initial formation of an inactive toxin-ganglioside complex which subsequently migrates and is somehow transformed into an active species which involves relocation within the two-dimensional structure of the membrane with direct perturbation of adenylate cyclase molecules (virtually irreversibly). These studies suggest new insights into the normal mechanisms by which hormone receptors modify membrane functions.", "contents": "Structure and function of cholera toxin and hormone receptors. The enterotoxin from Vibrio cholerae is a protein of 100,000 mol wt which stimulates adenylate cyclase activity ubiquitously. The binding of biologically active 125I-labeled choleragen to cell membranes is of extraordinary affinity and specificity. The binding may be restricted to membrane-bound ganglioside GM1. This ganglioside can be inserted into membranes from exogenous sources, and the increased toxin binding in such cells can be reflected by an increased sensitivity to the biological effects of the toxin. Features of the toxin-activated adenylate cyclase, including conversion of the enzyne to a GTP-sensitive state, and the increased sensitivity of activation by hormones, suggest analogies between the basic mechanism of action of choleragen and the events following binding of hormones to their receptors. The action of the toxin is probably not mediated through intermediary cytoplasmic events, suggesting that its effects are entirely due to processes involving the plasma membrane. The kinetics of activation of adenylate cyclase in erythrocytes from various species as well as in rat adipocytes suggest a direct interaction between toxin and the cyclase enzyme which is difficult to reconcile with catalytic mechanisms of adenylate cyclase activation. Direct evidence for this can be obtained from the comigration of toxin radioactivity with adenylate cyclase activity when toxin-activated membranes are dissolved in detergents and chromatographed on gel filtration columns. Agarose derivatives containing the \"active\" subunit of the toxin can specifically absorb adenylate cyclase activity, and specific antibodies against the choleragen can be used for selective immunoprecipitation of adenylate cyclase activity from detergent-solubilized preparations of activated membranes. It is proposed that toxin action involves the initial formation of an inactive toxin-ganglioside complex which subsequently migrates and is somehow transformed into an active species which involves relocation within the two-dimensional structure of the membrane with direct perturbation of adenylate cyclase molecules (virtually irreversibly). These studies suggest new insights into the normal mechanisms by which hormone receptors modify membrane functions."} {"id": "PMID:176539", "title": "Infection in the burned upper extremity.", "content": "Infection invariably accompanies thermal injury. The degree to which a patient is jeopardized by infection is related to the size and depth of the burn, the density and virulence of the microorganisms colonizing the burn wound, and the competence of his immune defenses. The aim of topical therapy is to limit microbial colonization of the burn wound to levels below those associated with invasive infection of the viable tissue beneath the eschar. The use of effective topical and systemic antimicrobial agents has been associated with the emergence of other bacterial, fungal, and viral infections and a delay in separation of the eschar, presumably caused by the suppression of bacterial d\u00e9bribement of the burn wound. The treatment of fractures in thermally injured patients may require compromise to permit optimal wound care and alertness toward the development of osteomyelitis. Because of the frequency of suppurative thrombophlebitis in burned patients, particular care is needed in the management of intravenous cannulae. The treatment of burns is largely the control of infection. Awareness of the septic complications of thermal injury and constant vigilance against them is critical in successful burn management.", "contents": "Infection in the burned upper extremity. Infection invariably accompanies thermal injury. The degree to which a patient is jeopardized by infection is related to the size and depth of the burn, the density and virulence of the microorganisms colonizing the burn wound, and the competence of his immune defenses. The aim of topical therapy is to limit microbial colonization of the burn wound to levels below those associated with invasive infection of the viable tissue beneath the eschar. The use of effective topical and systemic antimicrobial agents has been associated with the emergence of other bacterial, fungal, and viral infections and a delay in separation of the eschar, presumably caused by the suppression of bacterial d\u00e9bribement of the burn wound. The treatment of fractures in thermally injured patients may require compromise to permit optimal wound care and alertness toward the development of osteomyelitis. Because of the frequency of suppurative thrombophlebitis in burned patients, particular care is needed in the management of intravenous cannulae. The treatment of burns is largely the control of infection. Awareness of the septic complications of thermal injury and constant vigilance against them is critical in successful burn management."} {"id": "PMID:176543", "title": "Juvenile nasopharyngeal angiofibroma: radiographic aspects.", "content": "Because of consistent and unique radiographic features of JNA, it is not necessary, nor is it advisable, to biopsy these tumors to establish a diagnosis. In addition, the carotid arteriograms show the major feeding vessels to the lesion and also completely delineate the periphery of the tumor, thus establishing operability versus non-operability. If a JNA is treated by radiotherapy, the changes effected can be followed by carotid arteriography.", "contents": "Juvenile nasopharyngeal angiofibroma: radiographic aspects. Because of consistent and unique radiographic features of JNA, it is not necessary, nor is it advisable, to biopsy these tumors to establish a diagnosis. In addition, the carotid arteriograms show the major feeding vessels to the lesion and also completely delineate the periphery of the tumor, thus establishing operability versus non-operability. If a JNA is treated by radiotherapy, the changes effected can be followed by carotid arteriography."} {"id": "PMID:176544", "title": "Granular cell myoblastomas.", "content": "Granular cell myoblastoma is an uncommon benign tumor. The diagnosis is rarely suspected preoperatively, and the clinician is frequently baffled or frightened by an unfamiliar diagnosis. Twenty-eight patients with the diagnosis of granular cell myoblastoma presented for treatment at Richmond Eye and Ear Hospital and the Medical College of Virginia Hospitals between January 1, 1952, and December 31, 1974. The authors believe that this is one of the largest series of cases reported in the world literature. The tumor presents most often in the fourth decade of life and about equally in the sexes. Of interest is the nearly 5:1 predominance in the Negro race compared to the Caucasian race.", "contents": "Granular cell myoblastomas. Granular cell myoblastoma is an uncommon benign tumor. The diagnosis is rarely suspected preoperatively, and the clinician is frequently baffled or frightened by an unfamiliar diagnosis. Twenty-eight patients with the diagnosis of granular cell myoblastoma presented for treatment at Richmond Eye and Ear Hospital and the Medical College of Virginia Hospitals between January 1, 1952, and December 31, 1974. The authors believe that this is one of the largest series of cases reported in the world literature. The tumor presents most often in the fourth decade of life and about equally in the sexes. Of interest is the nearly 5:1 predominance in the Negro race compared to the Caucasian race."} {"id": "PMID:176545", "title": "Nasopharyngeal angiofibroma.", "content": "Nasopharyngeal angiofibromas have traditionally been difficult tumors to manage. Their extreme vascularity has led to excessive bleeding during surgical removal, which often obscured the surgical field and contributed to high recurrence rates because of incomplete removal. High recurrence rates have also been due to failure to recognize the full size and extent of these tumors preoperatively by routine physical examination and X-ray techniques. A combined experience of the authors with over 45 cases from the University of Michigan and the University of California, San Francisco, is presented to review the problems in management of these tumors and to present techniques of diagnosis and management which have been used to overcome some of these problems. The most important advances in diagnosis have been the radiographic techniques of laminagraphy and carotid angiography. Previously unrecognized tumor extensions into the areas surrounding the nasopharynx have been quite clearly demonstrated by these techniques. Improved surgical treatment of these tumors by wider surgical exposure and removal, utilizing multiple approaches when necessary, and by better control of bleeding by ligation and embolization of the main arterial supply, has led to fewer recurrences.", "contents": "Nasopharyngeal angiofibroma. Nasopharyngeal angiofibromas have traditionally been difficult tumors to manage. Their extreme vascularity has led to excessive bleeding during surgical removal, which often obscured the surgical field and contributed to high recurrence rates because of incomplete removal. High recurrence rates have also been due to failure to recognize the full size and extent of these tumors preoperatively by routine physical examination and X-ray techniques. A combined experience of the authors with over 45 cases from the University of Michigan and the University of California, San Francisco, is presented to review the problems in management of these tumors and to present techniques of diagnosis and management which have been used to overcome some of these problems. The most important advances in diagnosis have been the radiographic techniques of laminagraphy and carotid angiography. Previously unrecognized tumor extensions into the areas surrounding the nasopharynx have been quite clearly demonstrated by these techniques. Improved surgical treatment of these tumors by wider surgical exposure and removal, utilizing multiple approaches when necessary, and by better control of bleeding by ligation and embolization of the main arterial supply, has led to fewer recurrences."} {"id": "PMID:176546", "title": "Glomus tympanicum--excision by radical mastoidectomy exposure with autograft reconstruction.", "content": "Wide surgical exposure, total tumor removal and anatomic and functional reconstruction are the goals of tumor management. These goals are met by radical mastoidectomy exposure for the removal of glomus tympanicum tumors and reconstruction by autograft replacement of the posterior osseous canal, and if the tympanic membrane, malleus and incus are removed for tumor exposure, autograft replacement may also be accomplished. The history, physical findings, X-rays and details of surgical management of two patients with glomus tympanicum are reviewed. Wide removal of the posterior osseous canal, just lateral to the VIIth nerve with total replacement of this segment gives excellent exposure of the middle ear space and affords total reconstruction of the posterior osseous canal.", "contents": "Glomus tympanicum--excision by radical mastoidectomy exposure with autograft reconstruction. Wide surgical exposure, total tumor removal and anatomic and functional reconstruction are the goals of tumor management. These goals are met by radical mastoidectomy exposure for the removal of glomus tympanicum tumors and reconstruction by autograft replacement of the posterior osseous canal, and if the tympanic membrane, malleus and incus are removed for tumor exposure, autograft replacement may also be accomplished. The history, physical findings, X-rays and details of surgical management of two patients with glomus tympanicum are reviewed. Wide removal of the posterior osseous canal, just lateral to the VIIth nerve with total replacement of this segment gives excellent exposure of the middle ear space and affords total reconstruction of the posterior osseous canal."} {"id": "PMID:176561", "title": "[Value and relevance of metabolic function tests in the diagnosis of primary hyperparathyroidism (author's transl)].", "content": "Calcium, phosphate and alcaline phosphatase levels were determined in the serum of 29 patients with suspected primary hyperparathyroidism. Phosphate clearance according to Kyle, 24 hours urine hydroxyproline excretion during collagen free diet, the excretion of cAMP in the 24 h urine during calcium restricted diet were examined with regard to the diagnostic value and relevance as compared to the consumption of laboratory and staff time. The elevation of the serum calcium levels are not specific and only of minor diagnostic value. It has been found that the highest diagnostic value is given by the Kyle-test using 15 mg Ca ions/kg body weight. No false positive results were recorded. The excretion of hydroxyproline and calcium are only of limited value. Serum alcaline phosphatase and cAMP excretion have no diagnostic significance whereas concentration of serum phosphate may have some value.", "contents": "[Value and relevance of metabolic function tests in the diagnosis of primary hyperparathyroidism (author's transl)]. Calcium, phosphate and alcaline phosphatase levels were determined in the serum of 29 patients with suspected primary hyperparathyroidism. Phosphate clearance according to Kyle, 24 hours urine hydroxyproline excretion during collagen free diet, the excretion of cAMP in the 24 h urine during calcium restricted diet were examined with regard to the diagnostic value and relevance as compared to the consumption of laboratory and staff time. The elevation of the serum calcium levels are not specific and only of minor diagnostic value. It has been found that the highest diagnostic value is given by the Kyle-test using 15 mg Ca ions/kg body weight. No false positive results were recorded. The excretion of hydroxyproline and calcium are only of limited value. Serum alcaline phosphatase and cAMP excretion have no diagnostic significance whereas concentration of serum phosphate may have some value."} {"id": "PMID:176569", "title": "[Interaction of spin-labeled analogues of vitamin B 6 with the active site of apotransaminase].", "content": "Spin-labeled analogues of vitamin B6: 2, 2, 6, 6-tetramethyl-N-oxylpiperydinyl-4-(5' phosphopyridoxyl)-amine (1) and 2, 2, 6, 6-tetramethyl-N-oxyl-piperydinyl-4-(pyridoxal-5')-phosphate (II) are synthesized. There analogues were shown to interact in the equimolar ratio with the active site of cytosol aspartate transaminase. It was proved by CD-titration of apotransaminase with I and II and by competition between the coenzyme and synthesized analogues. The free valency of spin-labeled coenzymes immediately disappears after interaction with the apoenzyme due to iminoxyl group reduction. The binding of I and II with the apoenzyme is accompanied by oxidation of one of the inner cysteine residues. The reactivation of the modified apoenzyme with PLP is not less than 65% of original transaminase activity. The analysis of space-filling atomic models of synthesized compounds allows to conclude that the distance between the centre of pyridine ring of the coenzyme and the modified thiol group is not more than 8 A.", "contents": "[Interaction of spin-labeled analogues of vitamin B 6 with the active site of apotransaminase]. Spin-labeled analogues of vitamin B6: 2, 2, 6, 6-tetramethyl-N-oxylpiperydinyl-4-(5' phosphopyridoxyl)-amine (1) and 2, 2, 6, 6-tetramethyl-N-oxyl-piperydinyl-4-(pyridoxal-5')-phosphate (II) are synthesized. There analogues were shown to interact in the equimolar ratio with the active site of cytosol aspartate transaminase. It was proved by CD-titration of apotransaminase with I and II and by competition between the coenzyme and synthesized analogues. The free valency of spin-labeled coenzymes immediately disappears after interaction with the apoenzyme due to iminoxyl group reduction. The binding of I and II with the apoenzyme is accompanied by oxidation of one of the inner cysteine residues. The reactivation of the modified apoenzyme with PLP is not less than 65% of original transaminase activity. The analysis of space-filling atomic models of synthesized compounds allows to conclude that the distance between the centre of pyridine ring of the coenzyme and the modified thiol group is not more than 8 A."} {"id": "PMID:176570", "title": "[Study of the nitrogenase from Azotobacter vinelandii by the method of spin labels].", "content": "The interaction of nitrogenase with spin labels of four types have been studied. Conclusion about the presence of two SH-groups in the nitrogenase active site (one in Mo-Fe-protein and one in the Fe-protein) have been drawn from the correlation between the degree of inhibition of nitrogenfixing activity by the labels derived from p-Cl-Hg-benzoate and degree of binding of these labels to the nitrogenase molecule. Anaysis of EPR spectra of spin-labeled nitrogenase at 77 degrees K and at room temperature have shown that the labels bind to the free SH-groups and interact with iron containing center (ICC) of nitrogenase through the exchange mechanism. Distance between SH-group and ICC have been found to be 12 A. Spin labels derived from isocyanide have been bound directly to ICC in amount of 6--10 labels per one nitrogenase molecule. Due to the exchange interaction between these labels they give the singlet ESR spectra both at 77 degrees and at room temperature which is characteristic for the closely disposed labels. From this fact a conclusion have been drawn about the cluster structure of ICC. The labels derived from iodoacetamide ana maleimide bind SH- and NH2-groups of nitrogenase molecules. Analysis of temperature dependence of the effective rotational frequency of this labels have revealed a conformational transition in nitrogenase molecule at 19 degrees C, that has made it possible to explain the break in the Arrenius plots of enzyme activity.", "contents": "[Study of the nitrogenase from Azotobacter vinelandii by the method of spin labels]. The interaction of nitrogenase with spin labels of four types have been studied. Conclusion about the presence of two SH-groups in the nitrogenase active site (one in Mo-Fe-protein and one in the Fe-protein) have been drawn from the correlation between the degree of inhibition of nitrogenfixing activity by the labels derived from p-Cl-Hg-benzoate and degree of binding of these labels to the nitrogenase molecule. Anaysis of EPR spectra of spin-labeled nitrogenase at 77 degrees K and at room temperature have shown that the labels bind to the free SH-groups and interact with iron containing center (ICC) of nitrogenase through the exchange mechanism. Distance between SH-group and ICC have been found to be 12 A. Spin labels derived from isocyanide have been bound directly to ICC in amount of 6--10 labels per one nitrogenase molecule. Due to the exchange interaction between these labels they give the singlet ESR spectra both at 77 degrees and at room temperature which is characteristic for the closely disposed labels. From this fact a conclusion have been drawn about the cluster structure of ICC. The labels derived from iodoacetamide ana maleimide bind SH- and NH2-groups of nitrogenase molecules. Analysis of temperature dependence of the effective rotational frequency of this labels have revealed a conformational transition in nitrogenase molecule at 19 degrees C, that has made it possible to explain the break in the Arrenius plots of enzyme activity."} {"id": "PMID:176571", "title": "[Effect of chain length of dialdehyde oligonucleotides on the rate of their interaction with the three-dimensional matrix of polyacrylamide gel].", "content": "The kinetics of the reaction of periodate oxidized oligonucleotides with polyacrylhydrazide gel was studied. The rate of the reaction is proportional to (see article), where M is the molecular weight of the oligonucleotide for the permeable gels. The rate of the reaction with given oligonucleotide decrease as the number of crosslinks in the gel matrix increase; a dramatic decrease of the rate occurs when oligonucleotides become too large to penetrate into the matrix. The rate of the reactions with short oligonucleotides does not depend upon the viscosity of the medium. ESR method revealed a considerable decrease of the rotational mobility of oligonucleotides captured by the gel matrix. It has been shown also that an increase of the number of cross-links leads to a decrease of the rotational mobility of the gel chains.", "contents": "[Effect of chain length of dialdehyde oligonucleotides on the rate of their interaction with the three-dimensional matrix of polyacrylamide gel]. The kinetics of the reaction of periodate oxidized oligonucleotides with polyacrylhydrazide gel was studied. The rate of the reaction is proportional to (see article), where M is the molecular weight of the oligonucleotide for the permeable gels. The rate of the reaction with given oligonucleotide decrease as the number of crosslinks in the gel matrix increase; a dramatic decrease of the rate occurs when oligonucleotides become too large to penetrate into the matrix. The rate of the reactions with short oligonucleotides does not depend upon the viscosity of the medium. ESR method revealed a considerable decrease of the rotational mobility of oligonucleotides captured by the gel matrix. It has been shown also that an increase of the number of cross-links leads to a decrease of the rotational mobility of the gel chains."} {"id": "PMID:176573", "title": "[The regulator effect of fructose-1,6-diphosphate and cyclic adenosine monophosphate on protein and RNA synthesis by isolated mitochondria].", "content": "Effects of fructoso-1,6-diphosphate (FDP) and cyclic 3',5'-adenosine monophosphate (cAMP) on various steps of protein biosynthesis in isolated rat liver mitochondria were investigated. It was shown that FDP repressed and cAMP depressed the incorporation of both 14C-amino acid and [3H]uridine into mitochondrial polysomes. Cyclic 2',3'-adenosine monophosphate, a physiologically inactive analog of cAMP, had no depressing effect on the polysomes formation in mitochondria. Effects of FDP and cAMP on the synthesis of mitochondrial RNA at different periods of incubation (5, 10, 30 min) were studied. It was found that FDP repressed the high molecular weight mitochondrial RNA biosynthesis and prevented the mRNA formation. cAMP derepressed the FDP effect. Rifampicin prevented the derepressing action of cAMP. The rate of protein synthesis in the translation system isolated from mitochondria was affected neither by FDP nor by cAMP. Authors concluded that in the mammalian mitochondria the repression of protein synthesis by a glycolytic metabolite (FDP) and its derepression by cAMP represented regulatory mechanism acting at the transcription level like catabolite repression-derepression in microorganisms.", "contents": "[The regulator effect of fructose-1,6-diphosphate and cyclic adenosine monophosphate on protein and RNA synthesis by isolated mitochondria]. Effects of fructoso-1,6-diphosphate (FDP) and cyclic 3',5'-adenosine monophosphate (cAMP) on various steps of protein biosynthesis in isolated rat liver mitochondria were investigated. It was shown that FDP repressed and cAMP depressed the incorporation of both 14C-amino acid and [3H]uridine into mitochondrial polysomes. Cyclic 2',3'-adenosine monophosphate, a physiologically inactive analog of cAMP, had no depressing effect on the polysomes formation in mitochondria. Effects of FDP and cAMP on the synthesis of mitochondrial RNA at different periods of incubation (5, 10, 30 min) were studied. It was found that FDP repressed the high molecular weight mitochondrial RNA biosynthesis and prevented the mRNA formation. cAMP derepressed the FDP effect. Rifampicin prevented the derepressing action of cAMP. The rate of protein synthesis in the translation system isolated from mitochondria was affected neither by FDP nor by cAMP. Authors concluded that in the mammalian mitochondria the repression of protein synthesis by a glycolytic metabolite (FDP) and its derepression by cAMP represented regulatory mechanism acting at the transcription level like catabolite repression-derepression in microorganisms."} {"id": "PMID:176572", "title": "[Evolution of the DNA structure: direction, mechanism, rate].", "content": "On the basis of the analysis of frequencies of occurence of pyrimidines of different length, the degree of clustering of DNA of a hundred species belonging to different taxons has been determined. A tendency towards increase in the index of DNA clustering was revealed in the sequence: bacteria, invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which an increase in the degree of clustering of DNA in the process of progressive evolution of species may be due to accumulation of mutations, Pyr in equilibrium Pur transversions, resulting in an increase in the degree of asymmetry of the complementary chains of DNA. That this mechanism does exist is proved by a positive correlation between the degree of clustering of DNA and the degree of asymmetry of natural DNA chains. The mean frequency of mutation of vertebrates is about 4,6-10(-8) substitutions per nucleotide per year. Evolution of different groups of organisms may be accompanied with an increase in the rate of evolution of DNA structure. With the help of a special computer program, proceeding from the amino acid sequence of cytochromes c in 40 species belonging to different taxons, the degree of clustering of pyrimidines and the degree of asymmetry of complementary chains of DNA cistrons coding for cytochrome c was determined. A general tendency towards an increase in the mean values of the corresponding parametres of structure was found in the following: bacteria, invertebrates, fishes, amphibians, reptiles, birds and mammals. Thus, it was established that \"neutral\" amino acid substitutions in cytochromes are based on the selection of mutations leading to accumulation of pyrimidines in sense H-chain of DNA, and purines--in the corresponding mRNA. The frequency of mutation in cytochrome c of chordates is about 5,2-10(-8) of amino acid residues per year. It is assumed that the evolution modification of DNA structure may be due to increase in the disturbance stability of translation.", "contents": "[Evolution of the DNA structure: direction, mechanism, rate]. On the basis of the analysis of frequencies of occurence of pyrimidines of different length, the degree of clustering of DNA of a hundred species belonging to different taxons has been determined. A tendency towards increase in the index of DNA clustering was revealed in the sequence: bacteria, invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which an increase in the degree of clustering of DNA in the process of progressive evolution of species may be due to accumulation of mutations, Pyr in equilibrium Pur transversions, resulting in an increase in the degree of asymmetry of the complementary chains of DNA. That this mechanism does exist is proved by a positive correlation between the degree of clustering of DNA and the degree of asymmetry of natural DNA chains. The mean frequency of mutation of vertebrates is about 4,6-10(-8) substitutions per nucleotide per year. Evolution of different groups of organisms may be accompanied with an increase in the rate of evolution of DNA structure. With the help of a special computer program, proceeding from the amino acid sequence of cytochromes c in 40 species belonging to different taxons, the degree of clustering of pyrimidines and the degree of asymmetry of complementary chains of DNA cistrons coding for cytochrome c was determined. A general tendency towards an increase in the mean values of the corresponding parametres of structure was found in the following: bacteria, invertebrates, fishes, amphibians, reptiles, birds and mammals. Thus, it was established that \"neutral\" amino acid substitutions in cytochromes are based on the selection of mutations leading to accumulation of pyrimidines in sense H-chain of DNA, and purines--in the corresponding mRNA. The frequency of mutation in cytochrome c of chordates is about 5,2-10(-8) of amino acid residues per year. It is assumed that the evolution modification of DNA structure may be due to increase in the disturbance stability of translation."} {"id": "PMID:176580", "title": "[Reversible bactericidal defect of leukocytes. Pseudomonas meningitis in a child with diabetes mellitus (author's transl)].", "content": "A 3-year-old boy with diabetes mellitus contracted meningitis caused by Pseudomonas aeruginosa. The disease lasted for several months in spite of antibiotic treatment. Diabetes mellitus was poorly controlled and hypoglycemia often occured. Immunoglobulin levels were normal. Investigations of leukocyte functions showed (no bactericidal activity), decreased phagocytic activity and very low NBT dye reduction by neutrophils during phagocytosis. Under the administration of polymixin, leukocyte transfusions and stabilization of glycemia the pathological clinical and laboratory findings disappeared within three weeks. Serial investigations of leukocyte function showed a gradual recovery of normal activity.", "contents": "[Reversible bactericidal defect of leukocytes. Pseudomonas meningitis in a child with diabetes mellitus (author's transl)]. A 3-year-old boy with diabetes mellitus contracted meningitis caused by Pseudomonas aeruginosa. The disease lasted for several months in spite of antibiotic treatment. Diabetes mellitus was poorly controlled and hypoglycemia often occured. Immunoglobulin levels were normal. Investigations of leukocyte functions showed (no bactericidal activity), decreased phagocytic activity and very low NBT dye reduction by neutrophils during phagocytosis. Under the administration of polymixin, leukocyte transfusions and stabilization of glycemia the pathological clinical and laboratory findings disappeared within three weeks. Serial investigations of leukocyte function showed a gradual recovery of normal activity."} {"id": "PMID:176581", "title": "The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man.", "content": "In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found.", "contents": "The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found."} {"id": "PMID:176586", "title": "Human reovirus-like agent as the major pathogen associated with \"winter\" gastroenteritis in hospitalized infants and young children.", "content": "We found a human reovirus-like agent in the stools of 42 per cent of 143 infants and young children hospitalized with acute gastroenteritis between January, 1974, and June, 1975. Half the patients studied by electron microscopy and serologic technics had evidence of infection with the agent. The infection had a seasonal pattern: 59 per cent of those admitted during the cooler months (November to April) shed the agent, with a peak of 78 per cent in December, 1974, and January, 1975, combined. None of the patients admitted during the warmer months (May to October) shed the agent. None of 275 Escherichia coli isolates from 32 patients with diarrhea produced heat-labile enterotoxin, whereas 17 of the 32 had evidence of infection with the reovirus-like agent. In addition, 14 of 40 parents of 37 patients with diarrhea associated with the reovirus-like agent were also infected, but most infectious were inapparent. This agent appears to be the major cause of diarrheal illness in the young during the cooler months.", "contents": "Human reovirus-like agent as the major pathogen associated with \"winter\" gastroenteritis in hospitalized infants and young children. We found a human reovirus-like agent in the stools of 42 per cent of 143 infants and young children hospitalized with acute gastroenteritis between January, 1974, and June, 1975. Half the patients studied by electron microscopy and serologic technics had evidence of infection with the agent. The infection had a seasonal pattern: 59 per cent of those admitted during the cooler months (November to April) shed the agent, with a peak of 78 per cent in December, 1974, and January, 1975, combined. None of the patients admitted during the warmer months (May to October) shed the agent. None of 275 Escherichia coli isolates from 32 patients with diarrhea produced heat-labile enterotoxin, whereas 17 of the 32 had evidence of infection with the reovirus-like agent. In addition, 14 of 40 parents of 37 patients with diarrhea associated with the reovirus-like agent were also infected, but most infectious were inapparent. This agent appears to be the major cause of diarrheal illness in the young during the cooler months."} {"id": "PMID:176592", "title": "Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters.", "content": "The postsynaptic actions of some neurotransmitters may be mediated through cyclic nucleotides and cyclic nucleotide-dependent phosphorylation of specific membrane proteins in postsynaptic cells. In addition to providing a molecular basis for the actions of several neurotransmitters and of certain drugs affecting behaviour, the model suggests a mechanism by which neurotransmitter signals may be converted into electrophysiological responses in postsynaptic cells.", "contents": "Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. The postsynaptic actions of some neurotransmitters may be mediated through cyclic nucleotides and cyclic nucleotide-dependent phosphorylation of specific membrane proteins in postsynaptic cells. In addition to providing a molecular basis for the actions of several neurotransmitters and of certain drugs affecting behaviour, the model suggests a mechanism by which neurotransmitter signals may be converted into electrophysiological responses in postsynaptic cells."} {"id": "PMID:176597", "title": "Intracellular forms of Epstein-Barr virus DNA in human tumour cells in vivo.", "content": "Tumour biopsies from Burkitt lymphoma patients, as well as human nasopharyngeal carcinoma cells growing in athymic mice, contain Epstein-Barr virus DNA as covalently closed circular DNA. In addition integrated viral DNA sequences seem to be present.", "contents": "Intracellular forms of Epstein-Barr virus DNA in human tumour cells in vivo. Tumour biopsies from Burkitt lymphoma patients, as well as human nasopharyngeal carcinoma cells growing in athymic mice, contain Epstein-Barr virus DNA as covalently closed circular DNA. In addition integrated viral DNA sequences seem to be present."} {"id": "PMID:176605", "title": "[Angiographic findings of tentorial branches of the internal carotid artery in gliomas infiltrating the tentorium (author's transl)].", "content": "The tentorial branches, originating from the cavernous portion of the internal carotid artery, showed pathological findings in two cases of brain tumors infiltrating the tentorium: a glioblastoma multiforme of the temporooccipital and basal regions and a medulloblastoma diffusely involving the cerebellar hemisphere, vermis brachium pontis and pons. The value and importance of the tentorial branches are emphasized in the diagnosis of glioma infiltrating the tentorium. The percentage of the visualization and the measurements of the visualized segment of these branches were described using selective internal carotid angiograms by the transfemoral catheter technic on 50 presumably normal adults. The percentage of the visualization of the tentorial branches was 24 percents and the average visualized segment measured 15 mm with a range of 5 to 30 mm on conventional angiograms.", "contents": "[Angiographic findings of tentorial branches of the internal carotid artery in gliomas infiltrating the tentorium (author's transl)]. The tentorial branches, originating from the cavernous portion of the internal carotid artery, showed pathological findings in two cases of brain tumors infiltrating the tentorium: a glioblastoma multiforme of the temporooccipital and basal regions and a medulloblastoma diffusely involving the cerebellar hemisphere, vermis brachium pontis and pons. The value and importance of the tentorial branches are emphasized in the diagnosis of glioma infiltrating the tentorium. The percentage of the visualization and the measurements of the visualized segment of these branches were described using selective internal carotid angiograms by the transfemoral catheter technic on 50 presumably normal adults. The percentage of the visualization of the tentorial branches was 24 percents and the average visualized segment measured 15 mm with a range of 5 to 30 mm on conventional angiograms."} {"id": "PMID:176607", "title": "[Endocrinological evaluation of sellar and suprasellar tumor cases (the 2nd report);--on postoperative pituitary function (author's transl)].", "content": "Fifty-six cases of sellar and suprasellar tumors were examined endocrinologically before and 3 weeks after surgery. 1) Hyporeactive cases of GH & ACTH were more frequently found in pituitary adenoma (100% and 23% respectively than in craniopharyngioma (86% and 14% respectively) before surgery. 2) GH secretion was impaired 3 weeks after surgery in all the cases. 3) ACTH secretion impaired preoperatively in 5 cases of pituitary adenoma improved in 3 cases 3 weeks after surgery. 4) Hyporeactivity of LH, FSH and TSH was found more frequently after surgery than before. 5) Almost all the cases of tuberculum sellae meningioma were endocrinologically normal before surgery. 6) ACTH, LH, FSH and prolactin secretion in cases of tuberculum sellae meningioma was not impaired after surgery, but TSH secretion in these cases became hyporeative in 4 of 5 cases after surgery.", "contents": "[Endocrinological evaluation of sellar and suprasellar tumor cases (the 2nd report);--on postoperative pituitary function (author's transl)]. Fifty-six cases of sellar and suprasellar tumors were examined endocrinologically before and 3 weeks after surgery. 1) Hyporeactive cases of GH & ACTH were more frequently found in pituitary adenoma (100% and 23% respectively than in craniopharyngioma (86% and 14% respectively) before surgery. 2) GH secretion was impaired 3 weeks after surgery in all the cases. 3) ACTH secretion impaired preoperatively in 5 cases of pituitary adenoma improved in 3 cases 3 weeks after surgery. 4) Hyporeactivity of LH, FSH and TSH was found more frequently after surgery than before. 5) Almost all the cases of tuberculum sellae meningioma were endocrinologically normal before surgery. 6) ACTH, LH, FSH and prolactin secretion in cases of tuberculum sellae meningioma was not impaired after surgery, but TSH secretion in these cases became hyporeative in 4 of 5 cases after surgery."} {"id": "PMID:176611", "title": "Electrophysiologic changes in uremic neuropathy after successful renal transplantation.", "content": "The pattern of electrophysiologic abnormalities in uremic neuropathy was studied in 17 patients near the time of successful renal transplantation and for an average of 2 years (4 to 68 months) afterward. Initially, sensory and motor conduction velocities were reduced, distal latencies were lengthened, and evoked action potentials were reduced or dispersed. These abnormalities were most marked in clinically severe neuropathies and were consistent with the combined presence of axonal degeneration and segmental demyelination. Following transplantation, there was a sustained improvement in motor and sensory conduction velocities but less consistent improvement in evoked action potentials. In severe neuropathies, action potentials tended to remain reduced or absent. The results suggest that the main reason for improvement in the neuropathy is segmental remyelination, some fibers remaining degenerate in severe neuropathies. In four patients, late failure occurred in the transplanted kidney, which was accompanied by recurrence of neuropathy. In each patient, a second successful transplant effected improvement for a second time.", "contents": "Electrophysiologic changes in uremic neuropathy after successful renal transplantation. The pattern of electrophysiologic abnormalities in uremic neuropathy was studied in 17 patients near the time of successful renal transplantation and for an average of 2 years (4 to 68 months) afterward. Initially, sensory and motor conduction velocities were reduced, distal latencies were lengthened, and evoked action potentials were reduced or dispersed. These abnormalities were most marked in clinically severe neuropathies and were consistent with the combined presence of axonal degeneration and segmental demyelination. Following transplantation, there was a sustained improvement in motor and sensory conduction velocities but less consistent improvement in evoked action potentials. In severe neuropathies, action potentials tended to remain reduced or absent. The results suggest that the main reason for improvement in the neuropathy is segmental remyelination, some fibers remaining degenerate in severe neuropathies. In four patients, late failure occurred in the transplanted kidney, which was accompanied by recurrence of neuropathy. In each patient, a second successful transplant effected improvement for a second time."} {"id": "PMID:176614", "title": "Ovarian and adrenal steroid production in the postmenopausal woman.", "content": "Relative contribution of the ovaries and adrenals to the pool of steroids in postmenopausal women is still the subject of much controversy. Estradiol, delta4-androstenedione, and testosterone were assayed in peripheral blood, adrenal, and ovarian vein blood of 11 postmenopausal patients. Intravenous administration of hCG resulted in increased androgen production by the ovaries but not estrogens while intravenous administration of adrenocorticotrophic hormone did not result in the enhancement of ovarian and adrenal estrogens.", "contents": "Ovarian and adrenal steroid production in the postmenopausal woman. Relative contribution of the ovaries and adrenals to the pool of steroids in postmenopausal women is still the subject of much controversy. Estradiol, delta4-androstenedione, and testosterone were assayed in peripheral blood, adrenal, and ovarian vein blood of 11 postmenopausal patients. Intravenous administration of hCG resulted in increased androgen production by the ovaries but not estrogens while intravenous administration of adrenocorticotrophic hormone did not result in the enhancement of ovarian and adrenal estrogens."} {"id": "PMID:176623", "title": "Cellular metabolite distribution and the control of gluconeogenesis in the perfused isolated rat liver.", "content": "Glucose production was measured in isolated rat livers perfused with 100 ml of blood-free recirculating medium. The gluconeogenic rate using L-alanine as substrate was only 55% of that obtained with L-lactate. The steady-state concentration of gluconeogenic and tricarboxylic acid cycle intermediates were measured in freeze clamped biopsies. Livers perfused with L-lactate displayed higher concentrations of malate, alpha-glycerophosphate and beta-hydroxybutyrate probably as a result of a higher state of reduction of the nicotinamide system. Hexose-phosphate intermediates were also increased when L-lactate was the substrate. Phosphoenolpyruvate and 3-phosphoglycerate were considerably elevated when L-alanine was the glucose precursor. Livers perfused with L-lactate displayed higher cytosolic concentration of all the tricarboxylic acid cycle intermediates except oxaloacetate while glutamate was slightly and aspartate considerably higher when alanine was the substrate. In the mitochondrial compartment the pattern of distribution tended to be the opposite; that is, livers perfused with L-lactate showed lower concentrations of all the intermediates except alpha-ketoglutarate. The mitochondrial: cytosolic metabolite gradients of all the intermediates whose distribution was studied were higher in livers perfused with L-alanine. The relevance of these findings to the observed differences in the gluconeogenic fluxes are discussed.", "contents": "Cellular metabolite distribution and the control of gluconeogenesis in the perfused isolated rat liver. Glucose production was measured in isolated rat livers perfused with 100 ml of blood-free recirculating medium. The gluconeogenic rate using L-alanine as substrate was only 55% of that obtained with L-lactate. The steady-state concentration of gluconeogenic and tricarboxylic acid cycle intermediates were measured in freeze clamped biopsies. Livers perfused with L-lactate displayed higher concentrations of malate, alpha-glycerophosphate and beta-hydroxybutyrate probably as a result of a higher state of reduction of the nicotinamide system. Hexose-phosphate intermediates were also increased when L-lactate was the substrate. Phosphoenolpyruvate and 3-phosphoglycerate were considerably elevated when L-alanine was the glucose precursor. Livers perfused with L-lactate displayed higher cytosolic concentration of all the tricarboxylic acid cycle intermediates except oxaloacetate while glutamate was slightly and aspartate considerably higher when alanine was the substrate. In the mitochondrial compartment the pattern of distribution tended to be the opposite; that is, livers perfused with L-lactate showed lower concentrations of all the intermediates except alpha-ketoglutarate. The mitochondrial: cytosolic metabolite gradients of all the intermediates whose distribution was studied were higher in livers perfused with L-alanine. The relevance of these findings to the observed differences in the gluconeogenic fluxes are discussed."} {"id": "PMID:176624", "title": "The relationship between the rate of rise of isometric tension and motor unit recruitment in a human forearm muscle.", "content": "The recruitment properties of single motor units from the human extensor indicis muscle were investigated during voluntary isometric contractions of different rate of rise but equal amplitude. Both the electrical and the contractile events associated with recruitment were analyzed. The threshold force of recruitment (measured as the total muscle force at firing onset) decreased with increasing rate of rise of isometric tension. This was consistently found for all units. Differences between low and high threshold units indicating a preferential tonic or phasic mode of activation were not observed. The contractile events associated with recruitment were analyzed analoguously to the electrical events. For this purpose, muscle force was measured at the time of the first twitch as it was measured at the time of the first spike. This separate measurement of the electrical and mechanical recruitment of a unit is necessary, because during a change of muscle force, force is different at firing onset and during the subsequent twitch contraction. Muscle tension at the time of the peak of the first twitch contraction was calculated from measurements of the twitch concentration time of the single motor units. In contrast to firing onset, the peak of the first twitch of a motor unit occurs at approximately the same muscle tension no matter how fast the contraction is performed. This is the consequence of the result that the average decrease of the threshold force of recruitment at successively faster contraction has the same value as the corresponding increase of total muscle force during the mean contraction time of the motor units. On the basis of this precise matching between these two changes, the mechanical recruitment of motor units occurs at approximately the same force level irrespective of the rate of rise of tension.", "contents": "The relationship between the rate of rise of isometric tension and motor unit recruitment in a human forearm muscle. The recruitment properties of single motor units from the human extensor indicis muscle were investigated during voluntary isometric contractions of different rate of rise but equal amplitude. Both the electrical and the contractile events associated with recruitment were analyzed. The threshold force of recruitment (measured as the total muscle force at firing onset) decreased with increasing rate of rise of isometric tension. This was consistently found for all units. Differences between low and high threshold units indicating a preferential tonic or phasic mode of activation were not observed. The contractile events associated with recruitment were analyzed analoguously to the electrical events. For this purpose, muscle force was measured at the time of the first twitch as it was measured at the time of the first spike. This separate measurement of the electrical and mechanical recruitment of a unit is necessary, because during a change of muscle force, force is different at firing onset and during the subsequent twitch contraction. Muscle tension at the time of the peak of the first twitch contraction was calculated from measurements of the twitch concentration time of the single motor units. In contrast to firing onset, the peak of the first twitch of a motor unit occurs at approximately the same muscle tension no matter how fast the contraction is performed. This is the consequence of the result that the average decrease of the threshold force of recruitment at successively faster contraction has the same value as the corresponding increase of total muscle force during the mean contraction time of the motor units. On the basis of this precise matching between these two changes, the mechanical recruitment of motor units occurs at approximately the same force level irrespective of the rate of rise of tension."} {"id": "PMID:176630", "title": "The sensitivity of RNA polymerases I and II from Novikoff hepatoma (N1S1) cells to 3'-deoxyadenosine 5'-triphosphate.", "content": "The synthesis of ribosomal precursor RNA in Novikoff hepatoma (N1S1) cells is very sensitive to cordycepin (3'-dA). The synthesis of hnRNA, however, is resistant to inhibition concentrations of 3'-dA that completely block the synthesis of 45S ribosomal RNA precursor. We have examined the RNA polymerases present in these cultured cells with regard to their sensitivity to cordycepin 5'-triphosphate (3'-dATP) in an effort to explain the differential inhibition of RNA synthesis observed in vivo. RNA polymerases I and II were characterized on the basis of their chromatographic behavior on DEAE-Sephadex, as well as the response of their enzymatic activities to ionic strength, the divalent metal ions Mn2+ and Mg2+, and the toxin alpha-amanitin. For both enzymes the inhibition of in vitro RNA synthesis by 3'-dATP was competitive for ATP. The km values for ATP and the K1 values for 3'-dATP for the two enzymes were quite similar. RNA polymerase II, the enzyme presumed responsible for hnRNA synthesis, was actually slightly more sensitive to 3'-dATP than RNA polymerase I, the enzyme presumed responsible for ribosomal precursor RNA synthesis. Similar data were obtained when the RNA polymerases were assayed in isolated nuclei. These results indicate that the differential inhibition of RNA synthesis caused by 3'-dA in vivo cannot be simply explained by differential sensitivity of RNA polymerases I and II to 3'-dATP.", "contents": "The sensitivity of RNA polymerases I and II from Novikoff hepatoma (N1S1) cells to 3'-deoxyadenosine 5'-triphosphate. The synthesis of ribosomal precursor RNA in Novikoff hepatoma (N1S1) cells is very sensitive to cordycepin (3'-dA). The synthesis of hnRNA, however, is resistant to inhibition concentrations of 3'-dA that completely block the synthesis of 45S ribosomal RNA precursor. We have examined the RNA polymerases present in these cultured cells with regard to their sensitivity to cordycepin 5'-triphosphate (3'-dATP) in an effort to explain the differential inhibition of RNA synthesis observed in vivo. RNA polymerases I and II were characterized on the basis of their chromatographic behavior on DEAE-Sephadex, as well as the response of their enzymatic activities to ionic strength, the divalent metal ions Mn2+ and Mg2+, and the toxin alpha-amanitin. For both enzymes the inhibition of in vitro RNA synthesis by 3'-dATP was competitive for ATP. The km values for ATP and the K1 values for 3'-dATP for the two enzymes were quite similar. RNA polymerase II, the enzyme presumed responsible for hnRNA synthesis, was actually slightly more sensitive to 3'-dATP than RNA polymerase I, the enzyme presumed responsible for ribosomal precursor RNA synthesis. Similar data were obtained when the RNA polymerases were assayed in isolated nuclei. These results indicate that the differential inhibition of RNA synthesis caused by 3'-dA in vivo cannot be simply explained by differential sensitivity of RNA polymerases I and II to 3'-dATP."} {"id": "PMID:176631", "title": "A sedimentation study of the interaction of superhelical SV40 DNA with H1 histone.", "content": "By moving boundary sedimentation it is shown that the interaction of H1 histone with superhelical circular SV40 DNA results in the formation of giant heterogeneous aggregates. The size of these aggregates grows with increasing H1 concentration. s20,w values of some 10 000 S were measured. As compared with open relaxed circular DNA a preferential interaction of superhelical DNA with H1 histone is observed, irrespective of the sign of the superhelical turns which was reversed by the addition to DNA of ethidium bromide. The addition to the H1 complexed aggregates of ethidium bromide effects a progressive breakdown of the aggregates. Furthermore, the superhelicity of DNA is not changed by the addition of small amounts of H1 histone.", "contents": "A sedimentation study of the interaction of superhelical SV40 DNA with H1 histone. By moving boundary sedimentation it is shown that the interaction of H1 histone with superhelical circular SV40 DNA results in the formation of giant heterogeneous aggregates. The size of these aggregates grows with increasing H1 concentration. s20,w values of some 10 000 S were measured. As compared with open relaxed circular DNA a preferential interaction of superhelical DNA with H1 histone is observed, irrespective of the sign of the superhelical turns which was reversed by the addition to DNA of ethidium bromide. The addition to the H1 complexed aggregates of ethidium bromide effects a progressive breakdown of the aggregates. Furthermore, the superhelicity of DNA is not changed by the addition of small amounts of H1 histone."} {"id": "PMID:176629", "title": "[Leucaemoid reaction due to cytomegalovirus infection in a new born infant (author's transl)].", "content": "A newborn infant with low birth weight, jaundice, petechiae of the skin and enlargement of spleen and liver is presented. His general condition was severe and progressive aggravation of it was noticed. Bilirubin levels was up to 44 mg/100 ml, most of it indirect and severe anaemia was present. Furthermore leucaemoid reaction of the white cells was developed. Inclusion bodies in the urine and increased title of complement fixation antibodies in the peripheral blood were detected. The diagnosis of cytomegalovirus disease was established. The patient, when he was forty days old, seemed to be fairly well, but mental retardation was noticed, which persisted at the fifth month of his age.", "contents": "[Leucaemoid reaction due to cytomegalovirus infection in a new born infant (author's transl)]. A newborn infant with low birth weight, jaundice, petechiae of the skin and enlargement of spleen and liver is presented. His general condition was severe and progressive aggravation of it was noticed. Bilirubin levels was up to 44 mg/100 ml, most of it indirect and severe anaemia was present. Furthermore leucaemoid reaction of the white cells was developed. Inclusion bodies in the urine and increased title of complement fixation antibodies in the peripheral blood were detected. The diagnosis of cytomegalovirus disease was established. The patient, when he was forty days old, seemed to be fairly well, but mental retardation was noticed, which persisted at the fifth month of his age."} {"id": "PMID:176644", "title": "[Synovial sarcoma of the oral cavity (foramen caecum) Report of a case and review of the literature].", "content": "The twelft case of synovial sarcoma of the neck originated in the base of the tongue at the foramen caecum is reported. The patient, a 21 year old man developed a 7 cm. tumor after a 5 month period. A radical neck disection revealed metastases to lymph nodes, to spinal chain and residual tumor infiltrating the parotid gland. The subsequent X-ray studies showed metastases to lung. The patient is well 1 year after surgery. The pathogenesis of synovial sarcomas in regions so distant from normal synovial elements as the neck and other sites is not clear. In the present case and in those reported previously it is probable that the arise from synovial cell lining tendon sheaths or adventitious bursae in the neck.", "contents": "[Synovial sarcoma of the oral cavity (foramen caecum) Report of a case and review of the literature]. The twelft case of synovial sarcoma of the neck originated in the base of the tongue at the foramen caecum is reported. The patient, a 21 year old man developed a 7 cm. tumor after a 5 month period. A radical neck disection revealed metastases to lymph nodes, to spinal chain and residual tumor infiltrating the parotid gland. The subsequent X-ray studies showed metastases to lung. The patient is well 1 year after surgery. The pathogenesis of synovial sarcomas in regions so distant from normal synovial elements as the neck and other sites is not clear. In the present case and in those reported previously it is probable that the arise from synovial cell lining tendon sheaths or adventitious bursae in the neck."} {"id": "PMID:176647", "title": "[Serum glucose-6-phosphatase activity in thyrotoxicosis patients both fasting and following a sugar load].", "content": "A study was made of the activity of glucose-6-phosphatase in the blood serum of patients with thyrotoxicosis and in healthy persons and of its change after glucose loading. The activity of the enzyme on fasting stomach proved to be increased in the patients with throtoxicosis. The activity of the enzyme remained unchanged in these persons after glucose loading both during the hyperglycemic and the hypoglycemic phases of the glycemic curve; it remained high till the end of the observation period. In healthy persons, during the hypoglycemic phase of the glycemic curve, the activity of the enzyme was doubled, and at the height of hyperglycemia, after glucose loading- it was no different from the initial value. It is supposed that a high activity of the enzyme in the patients with thyrotoxicosis was associated with reduction in glycogen content in the tissues, along with activation of the glycogenolysis and gluconeongenesis processes.", "contents": "[Serum glucose-6-phosphatase activity in thyrotoxicosis patients both fasting and following a sugar load]. A study was made of the activity of glucose-6-phosphatase in the blood serum of patients with thyrotoxicosis and in healthy persons and of its change after glucose loading. The activity of the enzyme on fasting stomach proved to be increased in the patients with throtoxicosis. The activity of the enzyme remained unchanged in these persons after glucose loading both during the hyperglycemic and the hypoglycemic phases of the glycemic curve; it remained high till the end of the observation period. In healthy persons, during the hypoglycemic phase of the glycemic curve, the activity of the enzyme was doubled, and at the height of hyperglycemia, after glucose loading- it was no different from the initial value. It is supposed that a high activity of the enzyme in the patients with thyrotoxicosis was associated with reduction in glycogen content in the tissues, along with activation of the glycogenolysis and gluconeongenesis processes."} {"id": "PMID:176648", "title": "[The relationship between the level of hypophyseal adrenocorticotropic activity and the character of the tissue distribution of exogenously labeled ACTH].", "content": "Experiments were conducted on rats--intact, adrenalectomized and dexamethasone-treated; a study was made of the dynamics of incorporation into the kidneys, liver, adrenal glands, the thyroid gland and elmination from the blood plasma of iodated corticotropine of the hypophysis (Hum-ACTHid-28, Richter). It was revealed that the character of incorporation and elimination of the exogenous labeled ACTH depended on the state of the adrenocorticotropic activity of the hypophysis of the recipient rats. The period of semielimination of the iodated corticotropin of the hypophysis from the blood plasma of intact rats constituted 11.2 minutes. The hormone was not included into the parenchyma of the adrenal cortex. The rate of excretion through the kidney and catabolism in the liver of labeled ACTH increased with elevation of the level of endogenous ACTH in the blood. The period of semiexcretion of ACTH-I131 from the blood plasma of adrenalectomized animals constuted 6.4 min. With decrease of the level of endogenous ACTH in the blood due to the block of the hypophyseal secretion with decamethasone elimination of exogenous labeled hormone from the circulation was markedly retarded T1/2 = 17 min). Under these conditions ACTH-I131 was incorporated into the tissue of the adrenal cortex for 9 min. A conclusions was drawn that the period of semielimination of the exogenous iodated ACTH could be used as a criterion for the assessment of the adrenocorticotropic activity of the hypophysis of the animals-recipients.", "contents": "[The relationship between the level of hypophyseal adrenocorticotropic activity and the character of the tissue distribution of exogenously labeled ACTH]. Experiments were conducted on rats--intact, adrenalectomized and dexamethasone-treated; a study was made of the dynamics of incorporation into the kidneys, liver, adrenal glands, the thyroid gland and elmination from the blood plasma of iodated corticotropine of the hypophysis (Hum-ACTHid-28, Richter). It was revealed that the character of incorporation and elimination of the exogenous labeled ACTH depended on the state of the adrenocorticotropic activity of the hypophysis of the recipient rats. The period of semielimination of the iodated corticotropin of the hypophysis from the blood plasma of intact rats constituted 11.2 minutes. The hormone was not included into the parenchyma of the adrenal cortex. The rate of excretion through the kidney and catabolism in the liver of labeled ACTH increased with elevation of the level of endogenous ACTH in the blood. The period of semiexcretion of ACTH-I131 from the blood plasma of adrenalectomized animals constuted 6.4 min. With decrease of the level of endogenous ACTH in the blood due to the block of the hypophyseal secretion with decamethasone elimination of exogenous labeled hormone from the circulation was markedly retarded T1/2 = 17 min). Under these conditions ACTH-I131 was incorporated into the tissue of the adrenal cortex for 9 min. A conclusions was drawn that the period of semielimination of the exogenous iodated ACTH could be used as a criterion for the assessment of the adrenocorticotropic activity of the hypophysis of the animals-recipients."} {"id": "PMID:176649", "title": "[The ultrastructure of pancreatic beta cells in dithizone diabetes and its prevention by sodium diethyldithiocarbamate].", "content": "Administration of a nondiabetogenic complex-former-sodium diethyldithiocarbamate (SDEDTC) to rabbits prevented the appearance in beta-cells of the insular apparatus of histological and ultramicroscopic changes with the subsequent administration of a potent diabetogenic agent-ditisone. SDEDTC blocked the insular zinc and prevented ditisone from forming in the islets a complex with this metal producing a destructive action of beta-cells.", "contents": "[The ultrastructure of pancreatic beta cells in dithizone diabetes and its prevention by sodium diethyldithiocarbamate]. Administration of a nondiabetogenic complex-former-sodium diethyldithiocarbamate (SDEDTC) to rabbits prevented the appearance in beta-cells of the insular apparatus of histological and ultramicroscopic changes with the subsequent administration of a potent diabetogenic agent-ditisone. SDEDTC blocked the insular zinc and prevented ditisone from forming in the islets a complex with this metal producing a destructive action of beta-cells."} {"id": "PMID:176650", "title": "[The effect of experimental thyrotoxicosis on the state of the hypothalamo-hypophyseo-adrenal system in rats].", "content": "Experiments were conducted on male albino rats (298); a study was made of the effect of experimental thyrotoxicosis of various severity on the state of the hypothalamo-hypophyseal-adrenal system. It was found that the hypothalamo-hypophyseal-adrenal system responded differently to the excess of thyroid hormone, depending on the strength and duration of action. Mild thyrotoxicosis was accompanied by its activation expressed in increased CRF of the hypothalamic extracts, a reduction of the ACTH in the hypophysis and a fall of ascorbic acid content in the adrenal glands. Severe and prolonged thyrotoxicosis was accompanied by a depression of the hypothalamo-hypophysio-adrenal system function. It was concluded that the action of thyroid hormones on the CRF secretion served as the leading mechanism of the mentioned reactions.", "contents": "[The effect of experimental thyrotoxicosis on the state of the hypothalamo-hypophyseo-adrenal system in rats]. Experiments were conducted on male albino rats (298); a study was made of the effect of experimental thyrotoxicosis of various severity on the state of the hypothalamo-hypophyseal-adrenal system. It was found that the hypothalamo-hypophyseal-adrenal system responded differently to the excess of thyroid hormone, depending on the strength and duration of action. Mild thyrotoxicosis was accompanied by its activation expressed in increased CRF of the hypothalamic extracts, a reduction of the ACTH in the hypophysis and a fall of ascorbic acid content in the adrenal glands. Severe and prolonged thyrotoxicosis was accompanied by a depression of the hypothalamo-hypophysio-adrenal system function. It was concluded that the action of thyroid hormones on the CRF secretion served as the leading mechanism of the mentioned reactions."} {"id": "PMID:176656", "title": "Solid tumor models for the assessment of different treatment modalities: systematics of response to radiotherapy and chemotherapy.", "content": "The change of tumor volumes (efficiency) with local tumor radiation doses from 375R to 3750R and 5-fluorouracil (5-FUra) from 50 to 250 mg/kg was assessed in rats bearing hepatoma 3924A. The data were analyzed utilizing a chi2 technique which fits the logarithmic volume response to polynomials. This provided greater flexibility in selecting different mathematical forms, and allows more accurate description of tumor changes after treatment than the least squares analysis previously used. Quantitative information can be obtained on one tumor following treatment by this method. This information is more analogous to the management of a patient with a solid tumor. The results show a continuous increase in efficiency of radiation throughout the radiation dose range from 375R to 3750R. The efficiency of 5-FUra increased slightly but did not continue to increase with doses of 5-FUra higher than 150 mg/kg. This suggests that factors such as toxicity to the host may prevent further increases of the effectiveness of 5-FUra. The time of minimum tumor volume change after radiation was approximately 6 days and for 5-FUra, 6 days. The time for maximum tumor volume change for 5-FUra was 12 days. There was a slight trend upward for maximum growth for increasing radiation doses from 18 to 22 days. The time of occurrence of both minimum and maximum tumor volume change after treatment showed little relationship to increasing doses of radiation and 5-FUra. Parallel studies have shown that the maximum rate of tumor volume change occurs shortly after the recovery of the host from the effect of 5-FUra. It is feasible, therefore, to use chemotherapy alone or in combination with radiotherapy, and optimize the scheduling of these treatment modalities with recovery of the host from previous therapy.", "contents": "Solid tumor models for the assessment of different treatment modalities: systematics of response to radiotherapy and chemotherapy. The change of tumor volumes (efficiency) with local tumor radiation doses from 375R to 3750R and 5-fluorouracil (5-FUra) from 50 to 250 mg/kg was assessed in rats bearing hepatoma 3924A. The data were analyzed utilizing a chi2 technique which fits the logarithmic volume response to polynomials. This provided greater flexibility in selecting different mathematical forms, and allows more accurate description of tumor changes after treatment than the least squares analysis previously used. Quantitative information can be obtained on one tumor following treatment by this method. This information is more analogous to the management of a patient with a solid tumor. The results show a continuous increase in efficiency of radiation throughout the radiation dose range from 375R to 3750R. The efficiency of 5-FUra increased slightly but did not continue to increase with doses of 5-FUra higher than 150 mg/kg. This suggests that factors such as toxicity to the host may prevent further increases of the effectiveness of 5-FUra. The time of minimum tumor volume change after radiation was approximately 6 days and for 5-FUra, 6 days. The time for maximum tumor volume change for 5-FUra was 12 days. There was a slight trend upward for maximum growth for increasing radiation doses from 18 to 22 days. The time of occurrence of both minimum and maximum tumor volume change after treatment showed little relationship to increasing doses of radiation and 5-FUra. Parallel studies have shown that the maximum rate of tumor volume change occurs shortly after the recovery of the host from the effect of 5-FUra. It is feasible, therefore, to use chemotherapy alone or in combination with radiotherapy, and optimize the scheduling of these treatment modalities with recovery of the host from previous therapy."} {"id": "PMID:176652", "title": "[The functional activity of rat fetus adrenal cortex in monolayer tissue culture].", "content": "A study was made of the functional activity of the adrenal cortex in 15 1/2-, 18 1/2-, and 21 1/2-day rat fetuses and neonates. Adrenal tissue was incubated after its preliminary trypsinization at 37 degrees C for over 2 weeks with and without ACTH addition into the culture medium, in the amount of 0.1 U/ml. The corticosterone level was determined in the culture medium fluorimetrically. The activity of 3 beta-oxysteroid dehydrogenase was determined histochemically. Corticosterone was revealed in the culture medium. The activity of 3 beta-oxysteroid dehydrogenase was found in the cells of the cultivated adrenal glands. Addition of ACTH into the culture medium considerably increased the corticosterone level and elevated the activity of 3 beta-oxysteroid dehydrogenase. It can be considered on the basis of the aforesaid that cells of the primary culture of the adrenal cortex of rat fetuses aged 15 1/2-, 18 1/2-, and 21 1/2-days and of neonates could form, in the process of incubation, corticosterone from the endogenous substrates in the course of 11, 16, 8 and 13 cultivation days, respectively. The presence of ACTH in the culture medium for the adrenal glands of rat fetuses (of all the gestation periods under study) and of neonates intensified the steroidogenesis.", "contents": "[The functional activity of rat fetus adrenal cortex in monolayer tissue culture]. A study was made of the functional activity of the adrenal cortex in 15 1/2-, 18 1/2-, and 21 1/2-day rat fetuses and neonates. Adrenal tissue was incubated after its preliminary trypsinization at 37 degrees C for over 2 weeks with and without ACTH addition into the culture medium, in the amount of 0.1 U/ml. The corticosterone level was determined in the culture medium fluorimetrically. The activity of 3 beta-oxysteroid dehydrogenase was determined histochemically. Corticosterone was revealed in the culture medium. The activity of 3 beta-oxysteroid dehydrogenase was found in the cells of the cultivated adrenal glands. Addition of ACTH into the culture medium considerably increased the corticosterone level and elevated the activity of 3 beta-oxysteroid dehydrogenase. It can be considered on the basis of the aforesaid that cells of the primary culture of the adrenal cortex of rat fetuses aged 15 1/2-, 18 1/2-, and 21 1/2-days and of neonates could form, in the process of incubation, corticosterone from the endogenous substrates in the course of 11, 16, 8 and 13 cultivation days, respectively. The presence of ACTH in the culture medium for the adrenal glands of rat fetuses (of all the gestation periods under study) and of neonates intensified the steroidogenesis."} {"id": "PMID:176657", "title": "Thyrotropin-ganglioside interactions and their relationship to the structure and function of thyrotropin receptors.", "content": "Gangliosides inhibit 125I-labeled thyrotropin binding to the thyrotropin receptors on bovine thyroid plasma membranes, on guinea pig retro-orbital tissue plasma membranes, and on human adipocyte membranes. This inhibition by gangliosides is critically altered by the number and location of the sialic acid residues within the ganglioside structure, the efficacy of inhibition having the following order: GD1b greater than GT1 greater than GM1 greater than GM2 = GM3 greater than GD1a. The inhibition results from the interaction of thyrotropin and gangliosides, rather than the interaction of membrane and gangliosides. Fluorescence studies show that the inhibition is associated with a distinct conformational change of the thyrotropin molecule and that the progression from a \"noninhibitory conformation\" to an \"inhibitory conformation\" parallels exactly the order of effectiveness in inhibiting 125I-labeled thyrotropin binding. The ganglioside inhibition of 125I-labeled thyrotropin binding appears to be hormonally specific in that it is not affected by albumin, glucagon, insulin, prolactin, follicle-stimulating hormone, growth hormone, or corticotropin. The possibility that a ganglioside or ganglioside-like structure is a component of the thyrotropin receptor is suggested by the finding that gangliosides more complex than N-acetylneuraminylgalactosylglucosylceramide are present in bovine thyroid membranes in much higher quantities than have been previously found in extraneural tissue. The finding that the B component of cholera toxin, which also interacts with gangliosides, has a peptide sequence in common with the beta subunit of thyrotropin, suggests that thyrotropin and cholera toxin may be analogous in their mode of action on the membrane.", "contents": "Thyrotropin-ganglioside interactions and their relationship to the structure and function of thyrotropin receptors. Gangliosides inhibit 125I-labeled thyrotropin binding to the thyrotropin receptors on bovine thyroid plasma membranes, on guinea pig retro-orbital tissue plasma membranes, and on human adipocyte membranes. This inhibition by gangliosides is critically altered by the number and location of the sialic acid residues within the ganglioside structure, the efficacy of inhibition having the following order: GD1b greater than GT1 greater than GM1 greater than GM2 = GM3 greater than GD1a. The inhibition results from the interaction of thyrotropin and gangliosides, rather than the interaction of membrane and gangliosides. Fluorescence studies show that the inhibition is associated with a distinct conformational change of the thyrotropin molecule and that the progression from a \"noninhibitory conformation\" to an \"inhibitory conformation\" parallels exactly the order of effectiveness in inhibiting 125I-labeled thyrotropin binding. The ganglioside inhibition of 125I-labeled thyrotropin binding appears to be hormonally specific in that it is not affected by albumin, glucagon, insulin, prolactin, follicle-stimulating hormone, growth hormone, or corticotropin. The possibility that a ganglioside or ganglioside-like structure is a component of the thyrotropin receptor is suggested by the finding that gangliosides more complex than N-acetylneuraminylgalactosylglucosylceramide are present in bovine thyroid membranes in much higher quantities than have been previously found in extraneural tissue. The finding that the B component of cholera toxin, which also interacts with gangliosides, has a peptide sequence in common with the beta subunit of thyrotropin, suggests that thyrotropin and cholera toxin may be analogous in their mode of action on the membrane."} {"id": "PMID:176658", "title": "Sex differences in binding of human growth hormone to isolated rat hepatocytes.", "content": "Since liver is a target for growth hormone action, binding of 125I-labeled human growth hormone to enzymatically isolated rat hepatocytes was studied. Specific binding was shown with hepatocytes from both male and female animals. There was a single class of receptors for human growth hormone on cells from males (affinity constant, Ka = 1.16 x 10(9) liters/mole; sites per cell, q = 6200). In males, bovine growth hormone was almost as potent as human growth hormone in displacing bound 125I-labeled human growth hormone, while ovine prolactin was about 1000 times less potent. Cells from female rats bound more 125I-labeled human growth hormone than cells from males. The cells from females contained at least two classes of receptors for human growth hormone. The receptor of highest affinity had the same affinity for human growth hormone as the single receptor found in males (Ka = 0.96 x 10(9) liters/mole). However, there were three to four times as many of these receptors per cell in females (q = 21,000). In females, bovine growth hormone and ovine prolactin were both about 20 times less potent than human growth hormone. Treatment of male rats with estrone produced cells that show the same binding characteristics as females. These results indicate that human growth hormone binds to a somatogenic receptor in hepatocytes from male rats. In females and estrogen-treated males, the receptors that bind human growth hormone recognize lactogenic as well as somatogenic properties. This suggests that the lactogenic and growth-promoting effects of human growth hormone in the rat are mediated by different receptors.", "contents": "Sex differences in binding of human growth hormone to isolated rat hepatocytes. Since liver is a target for growth hormone action, binding of 125I-labeled human growth hormone to enzymatically isolated rat hepatocytes was studied. Specific binding was shown with hepatocytes from both male and female animals. There was a single class of receptors for human growth hormone on cells from males (affinity constant, Ka = 1.16 x 10(9) liters/mole; sites per cell, q = 6200). In males, bovine growth hormone was almost as potent as human growth hormone in displacing bound 125I-labeled human growth hormone, while ovine prolactin was about 1000 times less potent. Cells from female rats bound more 125I-labeled human growth hormone than cells from males. The cells from females contained at least two classes of receptors for human growth hormone. The receptor of highest affinity had the same affinity for human growth hormone as the single receptor found in males (Ka = 0.96 x 10(9) liters/mole). However, there were three to four times as many of these receptors per cell in females (q = 21,000). In females, bovine growth hormone and ovine prolactin were both about 20 times less potent than human growth hormone. Treatment of male rats with estrone produced cells that show the same binding characteristics as females. These results indicate that human growth hormone binds to a somatogenic receptor in hepatocytes from male rats. In females and estrogen-treated males, the receptors that bind human growth hormone recognize lactogenic as well as somatogenic properties. This suggests that the lactogenic and growth-promoting effects of human growth hormone in the rat are mediated by different receptors."} {"id": "PMID:176659", "title": "Secretion of macrophage neutral proteinase is enhanced by colchicine.", "content": "We have studied the effect of colchicine and related compounds on secretion of enzymes by thioglycollated-elicited mouse peritoneal macrophages in culture. Colchicine stimulated secretion of inducible neutral proteinase activities of elastase (EC 3.4.21.11), collagenase (EC 3.4.24.3), gelatinase (pepsin B; EC 3.4.23.2), and azocaseinase 2- to 6-fold for a period of several days, but inhibited the production and release of lysozyme (mucopeptide N-acetylmuramoylhydrolase; EC 3.2.1.17), a noninducible macrophage secretory product. Parallel changes were observed in cell morphology and secretion after treatment with colchicine, Colcemid, and vinblastine, but not with lumicolchicine, and these effects could be gradually reversed by withdrawal of colchicine. Cytochalasin B also stimulated secretion of elastase 2- to 3-fold but did not influence release of lysozyme. These results demonstrate that tubulin-binding drugs may have opposite effects in macrophages than those usually reported for other experimental systems and also provide evidence for the nonparallel discharge of different macrophage secretion products.", "contents": "Secretion of macrophage neutral proteinase is enhanced by colchicine. We have studied the effect of colchicine and related compounds on secretion of enzymes by thioglycollated-elicited mouse peritoneal macrophages in culture. Colchicine stimulated secretion of inducible neutral proteinase activities of elastase (EC 3.4.21.11), collagenase (EC 3.4.24.3), gelatinase (pepsin B; EC 3.4.23.2), and azocaseinase 2- to 6-fold for a period of several days, but inhibited the production and release of lysozyme (mucopeptide N-acetylmuramoylhydrolase; EC 3.2.1.17), a noninducible macrophage secretory product. Parallel changes were observed in cell morphology and secretion after treatment with colchicine, Colcemid, and vinblastine, but not with lumicolchicine, and these effects could be gradually reversed by withdrawal of colchicine. Cytochalasin B also stimulated secretion of elastase 2- to 3-fold but did not influence release of lysozyme. These results demonstrate that tubulin-binding drugs may have opposite effects in macrophages than those usually reported for other experimental systems and also provide evidence for the nonparallel discharge of different macrophage secretion products."} {"id": "PMID:176660", "title": "Androgen insensitivity in man: evidence for genetic heterogeneity.", "content": "We have studied ten phenotypically similar patients with complete androgen insensitivity. All of the patients tested had significantly elevated serum luteinizing hormone and plasma androgens within or above the normal adult male range. On the basis of specific dihydrotestosterone binding by skin fibroblasts, we identified two subgroups. Six patients from five different families had undetectable dihydrotestosterone binding, while four patients from two families had normal binding activity. Our results indicate that within the clinical syndrome of androgen insensitivity there are at least two distinct genetic variants. These variants may result from allelic mutations of the same X-linked gene specifying the dihydrotestosterone receptor or, alternatively, from mutations of separate genes both being essential for androgen action in responsive cells.", "contents": "Androgen insensitivity in man: evidence for genetic heterogeneity. We have studied ten phenotypically similar patients with complete androgen insensitivity. All of the patients tested had significantly elevated serum luteinizing hormone and plasma androgens within or above the normal adult male range. On the basis of specific dihydrotestosterone binding by skin fibroblasts, we identified two subgroups. Six patients from five different families had undetectable dihydrotestosterone binding, while four patients from two families had normal binding activity. Our results indicate that within the clinical syndrome of androgen insensitivity there are at least two distinct genetic variants. These variants may result from allelic mutations of the same X-linked gene specifying the dihydrotestosterone receptor or, alternatively, from mutations of separate genes both being essential for androgen action in responsive cells."} {"id": "PMID:176661", "title": "Assignment of the AK1:Np:ABO linkage group to human chromosome 9.", "content": "In man-Chinese hamster somatic cell hybrids the segregation patterns of the loci for 25 human enzyme markers and human chromosomes were studied. The results provide evidence for the localization of the gene for adenylate kinase-1 (AK1) on chromosome 9. Since the loci for the ABO blood group (ABO), nail-patella syndrome (Np), and AK1 are known to be linked in man, the ABO:Np:AK1 linkage group may be assigned to chromosome 9.", "contents": "Assignment of the AK1:Np:ABO linkage group to human chromosome 9. In man-Chinese hamster somatic cell hybrids the segregation patterns of the loci for 25 human enzyme markers and human chromosomes were studied. The results provide evidence for the localization of the gene for adenylate kinase-1 (AK1) on chromosome 9. Since the loci for the ABO blood group (ABO), nail-patella syndrome (Np), and AK1 are known to be linked in man, the ABO:Np:AK1 linkage group may be assigned to chromosome 9."} {"id": "PMID:176662", "title": "Genetic variation in serum low density lipoproteins and lipid levels in man.", "content": "Combined data from 10 different populations indicate that the serum cholesterol and triglyceride levels are higher in Ag(x-) than in Ag(x+) individuals. Although the differences were relatively small, they became more pronounced with increasing age. The Ag(x) antigen, which is associated with the serum low density lipoprotein, is genetically controlled and the present study therefore has revealed a small but significant effect of a single autosomal locus on lipids implicated in the pathogenesis of atherosclerosis. No explanation of the higher cholesterol and triglyceride levels in Ag(x-) than in Ag(x+) persons is apparent.", "contents": "Genetic variation in serum low density lipoproteins and lipid levels in man. Combined data from 10 different populations indicate that the serum cholesterol and triglyceride levels are higher in Ag(x-) than in Ag(x+) individuals. Although the differences were relatively small, they became more pronounced with increasing age. The Ag(x) antigen, which is associated with the serum low density lipoprotein, is genetically controlled and the present study therefore has revealed a small but significant effect of a single autosomal locus on lipids implicated in the pathogenesis of atherosclerosis. No explanation of the higher cholesterol and triglyceride levels in Ag(x-) than in Ag(x+) persons is apparent."} {"id": "PMID:176663", "title": "Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells.", "content": "We have studied cells dispersed with proteolytic enzymes from rheumatoid arthritic synovectomy specimens to determine the cell type(s) responsible for joint destruction. Initially 10-50% of these cells adhered to culture dishes within 24 hr and were of two main types: small, round cells and larger, stellate cells. During 1-4 days of culture, 5-25% had Fc receptors and 25-50% showed brisk phagocytosis. Daily producition, per 10(6) cells of collagenase (EC 3.4.24.3) (after trypsin pretreatment) was up to 70 mug of collagen fibrils lysed per min at 37 degrees (70 units), of prostaglandin (PGE2), up to about 1200 ng, and of lysozyme, up to about 100 mug. Under identical conditions of assay, fibroblasts grown from explants of synovium produced no detectable collagenase or lysozyme, and PGE2 was only 2-4 ng. With the dispersed cell preparations, macrophage markers (Fc receptors and lysozyme) were undetectable after 4 days and PGE2 decreased rapidly after about 7 more days. However, collagenase production continued for 3-25 weeks, and in some cultures, after cell passage. At these later stages, large, slow-growing stellate cells were predominant and could phagocytose carbon particles if incubated for greater than 6-8 hr. Indomethacin (14 muM) inhibited PGE2 but stimulated collagenase production whereas dexamethasone (10 nM) inhibited both. Production of PGE2 and collagenase in large amounts in vitro by these cells suggests that they may be involved in joint destruction in vivo. The precise origin of these synovial cells and the mechanisms responsible for the sustained production of collagenase at a high rate remain unidentified.", "contents": "Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. We have studied cells dispersed with proteolytic enzymes from rheumatoid arthritic synovectomy specimens to determine the cell type(s) responsible for joint destruction. Initially 10-50% of these cells adhered to culture dishes within 24 hr and were of two main types: small, round cells and larger, stellate cells. During 1-4 days of culture, 5-25% had Fc receptors and 25-50% showed brisk phagocytosis. Daily producition, per 10(6) cells of collagenase (EC 3.4.24.3) (after trypsin pretreatment) was up to 70 mug of collagen fibrils lysed per min at 37 degrees (70 units), of prostaglandin (PGE2), up to about 1200 ng, and of lysozyme, up to about 100 mug. Under identical conditions of assay, fibroblasts grown from explants of synovium produced no detectable collagenase or lysozyme, and PGE2 was only 2-4 ng. With the dispersed cell preparations, macrophage markers (Fc receptors and lysozyme) were undetectable after 4 days and PGE2 decreased rapidly after about 7 more days. However, collagenase production continued for 3-25 weeks, and in some cultures, after cell passage. At these later stages, large, slow-growing stellate cells were predominant and could phagocytose carbon particles if incubated for greater than 6-8 hr. Indomethacin (14 muM) inhibited PGE2 but stimulated collagenase production whereas dexamethasone (10 nM) inhibited both. Production of PGE2 and collagenase in large amounts in vitro by these cells suggests that they may be involved in joint destruction in vivo. The precise origin of these synovial cells and the mechanisms responsible for the sustained production of collagenase at a high rate remain unidentified."} {"id": "PMID:176664", "title": "Superinfection epithelial nasopharyngeal carcinoma cells with Epstein-Barr virus.", "content": "Attempts were made to superinfect epithelial explant cell cultures prepared from nasopharyngeal carcinomas with Epstein-Barr virus. Virus-specific markers were observed in such cultures 3 days after superinfection. In addition, expression of Epstein-Barr virus early antigens was observed in epithelial cell explant cultures treated with iododeoxyuridine. The results suggest that epithelial cells of at least certain nasopharyngeal carcinomas possess the receptor for the Epstein-Barr virus and that the latent virus genome can be induced from epithelial cells prepared from such tumors.", "contents": "Superinfection epithelial nasopharyngeal carcinoma cells with Epstein-Barr virus. Attempts were made to superinfect epithelial explant cell cultures prepared from nasopharyngeal carcinomas with Epstein-Barr virus. Virus-specific markers were observed in such cultures 3 days after superinfection. In addition, expression of Epstein-Barr virus early antigens was observed in epithelial cell explant cultures treated with iododeoxyuridine. The results suggest that epithelial cells of at least certain nasopharyngeal carcinomas possess the receptor for the Epstein-Barr virus and that the latent virus genome can be induced from epithelial cells prepared from such tumors."} {"id": "PMID:176668", "title": "Bidirectional regulation of lysosomal enzyme secretion and phagocytosis in human neutrophils by guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate.", "content": "The biologic roles of guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) in the secretion of lysosomal enzymes from, and in phagocytosis by, human neurtrophils were studied. Contact between neurophils and particulate immunologic reactants results in both phagocytosis of the particles and secretion of lysosomal enzymes. These cellular events are accompanied by the accumulation of cyclic GMP and require the presence of extracellular caclium. Acetylcholine, pilocarpine, and cyclic GMP enhance, whereas epinephrine, cyclic AMP, and/or dibutyryl cyclic AMP inhibit, both phagocytosis and lysosomal enzyme secretion. The stimulatory action of cholinergic agents and the inhibitory action of epinephrine are accompanied by the accumulation of cyclic GMP and cyclic AMP, respectively, in human neutrophils. The data suggest that cyclic GMP mediates whereas cyclic AMP inhibits the major functions of human neutrophils. Moreover, by virtue of their effects of cyclic nucleotide accumulation, autonomic neurohormones are capable of modulating human neutrophil function.", "contents": "Bidirectional regulation of lysosomal enzyme secretion and phagocytosis in human neutrophils by guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate. The biologic roles of guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) in the secretion of lysosomal enzymes from, and in phagocytosis by, human neurtrophils were studied. Contact between neurophils and particulate immunologic reactants results in both phagocytosis of the particles and secretion of lysosomal enzymes. These cellular events are accompanied by the accumulation of cyclic GMP and require the presence of extracellular caclium. Acetylcholine, pilocarpine, and cyclic GMP enhance, whereas epinephrine, cyclic AMP, and/or dibutyryl cyclic AMP inhibit, both phagocytosis and lysosomal enzyme secretion. The stimulatory action of cholinergic agents and the inhibitory action of epinephrine are accompanied by the accumulation of cyclic GMP and cyclic AMP, respectively, in human neutrophils. The data suggest that cyclic GMP mediates whereas cyclic AMP inhibits the major functions of human neutrophils. Moreover, by virtue of their effects of cyclic nucleotide accumulation, autonomic neurohormones are capable of modulating human neutrophil function."} {"id": "PMID:176669", "title": "Differences in simultaneous cylic adenosine monophosphate concentrations of various rat tissue after heroin administration.", "content": "Opiate administration has profound effects on neurotransmitter metabolism and neuroendocrine functions. Since cAMP is an intracellular metabolite common to the actions of many of the involved compounds stimulating distinct and specific membrane receptors, cAMP concentrations representative of in vivo conditions in heroin-treated and control animals were determined. Rats were sacrificed by immersion in liquid nitrogen 30 min after heroin injection. Tissue samples, dissected without thawing, were assayed by radioimmunoassay to determine cAMP/mg of protein. Comparisons between treated animals and sham-injected controls revealed significant cAMP concentration increases in hypothalamus, cerebral cortex, cerebellum, adrenal medulla, adrenal cortex, and liver (P less than 0.0005). Cyclic AMP concentrations in heart, skeletal muscle, kidney, and fat were not significantly different from controls. The increased tissue cAMP concentrations associated with the altered physiology of heroin administration apparently represent a pattern of integrated responses to the combination of opiate receptor binding and effects on neurotransmitter metabolism and circulating hormones.", "contents": "Differences in simultaneous cylic adenosine monophosphate concentrations of various rat tissue after heroin administration. Opiate administration has profound effects on neurotransmitter metabolism and neuroendocrine functions. Since cAMP is an intracellular metabolite common to the actions of many of the involved compounds stimulating distinct and specific membrane receptors, cAMP concentrations representative of in vivo conditions in heroin-treated and control animals were determined. Rats were sacrificed by immersion in liquid nitrogen 30 min after heroin injection. Tissue samples, dissected without thawing, were assayed by radioimmunoassay to determine cAMP/mg of protein. Comparisons between treated animals and sham-injected controls revealed significant cAMP concentration increases in hypothalamus, cerebral cortex, cerebellum, adrenal medulla, adrenal cortex, and liver (P less than 0.0005). Cyclic AMP concentrations in heart, skeletal muscle, kidney, and fat were not significantly different from controls. The increased tissue cAMP concentrations associated with the altered physiology of heroin administration apparently represent a pattern of integrated responses to the combination of opiate receptor binding and effects on neurotransmitter metabolism and circulating hormones."} {"id": "PMID:176670", "title": "Streptozotocin treatment of streptozotocin-induced islet cell adenomas in rats.", "content": "Hypoglycemic rats bearing insulin-secreting islet-cell adenomas produced by the combined action of streptozotocin and nicotinamide were treated with streptozotocin. Antitumor response was demonstrated by elevation of blood glucose, reduction in plasma and tumor IRI, and histopathologic changes in the beta-cell neoplasm. The rodent tumor model may serve as a predictive system for selection and investigation of mechanisms of action of future antitumor agents to be used in the treatment of malignant insulinoma in man.", "contents": "Streptozotocin treatment of streptozotocin-induced islet cell adenomas in rats. Hypoglycemic rats bearing insulin-secreting islet-cell adenomas produced by the combined action of streptozotocin and nicotinamide were treated with streptozotocin. Antitumor response was demonstrated by elevation of blood glucose, reduction in plasma and tumor IRI, and histopathologic changes in the beta-cell neoplasm. The rodent tumor model may serve as a predictive system for selection and investigation of mechanisms of action of future antitumor agents to be used in the treatment of malignant insulinoma in man."} {"id": "PMID:176672", "title": "Summer day camp for multihandicapped children.", "content": "A six-week enriched sensorimotor, communication, and recreational summer day camp for twenty multihandicapped preschool children is described. The program, planned and supervised by therapists and mental retardation counselors, provided training for students who worked as camp counselors. Each counselor was assigned to work with one child and family and was responsible for assessing, establishing goals, designing appropriate programs, attending the child throughout the day, and relating to the family. The camp provided a trial for use of the Functional Skills Profile (FSP), an assessment battery designed by physical and occupational therapists to measure performance changes in low functioning, developmentally handicapped persons in order to determine the value of therapy programs. The camp is evaluated in terms of improvement in the children, the effectiveness of the student training, and parent satisfaction.", "contents": "Summer day camp for multihandicapped children. A six-week enriched sensorimotor, communication, and recreational summer day camp for twenty multihandicapped preschool children is described. The program, planned and supervised by therapists and mental retardation counselors, provided training for students who worked as camp counselors. Each counselor was assigned to work with one child and family and was responsible for assessing, establishing goals, designing appropriate programs, attending the child throughout the day, and relating to the family. The camp provided a trial for use of the Functional Skills Profile (FSP), an assessment battery designed by physical and occupational therapists to measure performance changes in low functioning, developmentally handicapped persons in order to determine the value of therapy programs. The camp is evaluated in terms of improvement in the children, the effectiveness of the student training, and parent satisfaction."} {"id": "PMID:176673", "title": "REM sleep predicts subsequent food intake.", "content": "REM sleep time in a 12 hr period was found to predict accurately food intake in the subsequent 12 hr period in undisturbed cats fed ad lib. In all but one of the cats, the correlation between REM sleep and subsequent food intake was negative. REM sleep was a better predictor of food intake than either waking, slow wave sleep or previous food intake. Cats were then fed only during the 12 hr day period. It was found that REM sleep at night, during which no food was available, no longer predicted food intake.", "contents": "REM sleep predicts subsequent food intake. REM sleep time in a 12 hr period was found to predict accurately food intake in the subsequent 12 hr period in undisturbed cats fed ad lib. In all but one of the cats, the correlation between REM sleep and subsequent food intake was negative. REM sleep was a better predictor of food intake than either waking, slow wave sleep or previous food intake. Cats were then fed only during the 12 hr day period. It was found that REM sleep at night, during which no food was available, no longer predicted food intake."} {"id": "PMID:176674", "title": "Enhancement of attention in man with ACTH/MSH 4-10.", "content": "Normal men were infused for 4 hr with ACTH/MSH 4-10 or a control solution. Behavioral testing after the infusion indicated that subjects who received ACTH/MSH 4-10 were less anxious and had better visual memory than control subjects but the predominant effect of the heptapeptide was to increase visual attention. It was speculated that ACTH/MSH 4-10 may be uniquely coded for attentional functioning.", "contents": "Enhancement of attention in man with ACTH/MSH 4-10. Normal men were infused for 4 hr with ACTH/MSH 4-10 or a control solution. Behavioral testing after the infusion indicated that subjects who received ACTH/MSH 4-10 were less anxious and had better visual memory than control subjects but the predominant effect of the heptapeptide was to increase visual attention. It was speculated that ACTH/MSH 4-10 may be uniquely coded for attentional functioning."} {"id": "PMID:176677", "title": "Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation.", "content": "Two groups of young, healthy, nonathletic volunteers were subjected to selective sleep stage deprivation. Six subjects were deprived of stage 4 sleep and seven subjects of REM sleep. The stage 4 deprived group reported more musculoskeletal symptoms during the deprivation condition than did the REM deprived group. The stage 4 deprived group also showed a significant increase in muscle tenderness between the baseline and deprivation conditions and an altered pattern of overnight change in muscle tenderness in response to deprivation. The REM deprived group did not show either of these changes. These results are discussed in the light of the previously postulated relationship between NREM sleep disturbance and muscoloskeletal pain in patients with so-called \"Fibrositis syndrome.\"", "contents": "Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Two groups of young, healthy, nonathletic volunteers were subjected to selective sleep stage deprivation. Six subjects were deprived of stage 4 sleep and seven subjects of REM sleep. The stage 4 deprived group reported more musculoskeletal symptoms during the deprivation condition than did the REM deprived group. The stage 4 deprived group also showed a significant increase in muscle tenderness between the baseline and deprivation conditions and an altered pattern of overnight change in muscle tenderness in response to deprivation. The REM deprived group did not show either of these changes. These results are discussed in the light of the previously postulated relationship between NREM sleep disturbance and muscoloskeletal pain in patients with so-called \"Fibrositis syndrome.\""} {"id": "PMID:176684", "title": "[Malignant synovialoma (author's transl)].", "content": "Based upon 351 cases of malignant synovialoma from the literature and 12 own observations clinical and roentgenographic findings, differential diagnosis, therapy, and prognosis are discussed. Because of early recurrencies and metastases early diagnosis is most important for therapeutic results. By means of radical surgery and subsequent intensive irradiation of the previous tumor site and the draining lymphatics a 5-years survival rate of 30-50% can be achieved.", "contents": "[Malignant synovialoma (author's transl)]. Based upon 351 cases of malignant synovialoma from the literature and 12 own observations clinical and roentgenographic findings, differential diagnosis, therapy, and prognosis are discussed. Because of early recurrencies and metastases early diagnosis is most important for therapeutic results. By means of radical surgery and subsequent intensive irradiation of the previous tumor site and the draining lymphatics a 5-years survival rate of 30-50% can be achieved."} {"id": "PMID:176686", "title": "Hepatomography: an experimental technique using an emulsifier.", "content": "Hepatomography was performed by injecting emulsified Ethiodol into the hepatic artery of 9 beagles. The hepatogram was dense and remained long enough for diagnostic tomography. Contrast material was eliminated in part through the kidneys and disappeared from the liver within 24 hours after injection. The dogs were sacrificed 36 hours to 4 months after contrast injection. Longlasting ill effects were observed in only one dog which died of hepatitis. The death of this prompted the use of a more dilute emulsion which was beeter tolerated by all subsequent animals.", "contents": "Hepatomography: an experimental technique using an emulsifier. Hepatomography was performed by injecting emulsified Ethiodol into the hepatic artery of 9 beagles. The hepatogram was dense and remained long enough for diagnostic tomography. Contrast material was eliminated in part through the kidneys and disappeared from the liver within 24 hours after injection. The dogs were sacrificed 36 hours to 4 months after contrast injection. Longlasting ill effects were observed in only one dog which died of hepatitis. The death of this prompted the use of a more dilute emulsion which was beeter tolerated by all subsequent animals."} {"id": "PMID:176688", "title": "Aspirin as a quantitative acetylating reagent for the fatty acid oxygenase that forms prostaglandins.", "content": "A selective acetylation of the prostaglandin-forming fatty acid oxygenase (part of the prostaglandin \"synthetase\" system) occurs with 100 muM concentrations of aspirin (acetylsalicylic acid). The amount of acetylation, measured by counting the [3H]acetyl-protein formed, was proportional to the amount of active, functional oxygenase in a sample. When samples were aged to allow spontaneous inactivation of the oxygenase, the amount of acetylation was proportional to the remaining measurable activity rather than the initial amount of oxygenase protein in the sample. Diethyl dithiocarbamate inhibited the oxygenase activity, but did not interfere with the subsequent acetylation by aspirin. Indomethacin, on the other hand, appeared to inactivate the oxygenase in a manner that interfered only partially with the action of aspirin as an acetylating reagent. The amount of acetylation appeared to be dependent upon the amount of native, undenatured enzyme. The results suggest that the acetylation may be dependent upon an essential functional group or conformation of groups in the catalytic peptide chain(s) that can be destroyed during spontaneous inactivation of the oxygenase, and altered by indomethacin.", "contents": "Aspirin as a quantitative acetylating reagent for the fatty acid oxygenase that forms prostaglandins. A selective acetylation of the prostaglandin-forming fatty acid oxygenase (part of the prostaglandin \"synthetase\" system) occurs with 100 muM concentrations of aspirin (acetylsalicylic acid). The amount of acetylation, measured by counting the [3H]acetyl-protein formed, was proportional to the amount of active, functional oxygenase in a sample. When samples were aged to allow spontaneous inactivation of the oxygenase, the amount of acetylation was proportional to the remaining measurable activity rather than the initial amount of oxygenase protein in the sample. Diethyl dithiocarbamate inhibited the oxygenase activity, but did not interfere with the subsequent acetylation by aspirin. Indomethacin, on the other hand, appeared to inactivate the oxygenase in a manner that interfered only partially with the action of aspirin as an acetylating reagent. The amount of acetylation appeared to be dependent upon the amount of native, undenatured enzyme. The results suggest that the acetylation may be dependent upon an essential functional group or conformation of groups in the catalytic peptide chain(s) that can be destroyed during spontaneous inactivation of the oxygenase, and altered by indomethacin."} {"id": "PMID:176689", "title": "Prostaglandin biosynthesis and stimulation of cyclic AMP in primary monolayer cultures of epithelial cells from mouse mammary gland.", "content": "Cyclic AMP levels in primary monolayer cultures of epithelial cells prepared from mid-pregnant mice are stimulated by prostaglandin E1 and E2. Prostaglandin F1alpha and F2alpha have only a slight effect upon cyclic AMP levels. In the absence of phosphodiesterase inhibitors the rise in cyclic AMP produced by PGE1 is only transient and the levels return to normal within 30 minutes. High concentrations (16 mM) of theophylline are needed to prevent this decline, suggesting that the phosphodiesterase activity of epithelial cells in culture is high. However, theophylline alone produced only a small increase in basal cyclic AMP levels even over a 2-hour period indicating that basal cyclic AMP is turned over more slowly than cyclic AMP produced in response to stimulation with PGE1. Both PGE and PGF synthesis were monitored using radioimmunoassay procedures previously reported. The observed levels were found to decrease as cell density increased and were sensitive to the addition of agents such as collagen and naproxen.", "contents": "Prostaglandin biosynthesis and stimulation of cyclic AMP in primary monolayer cultures of epithelial cells from mouse mammary gland. Cyclic AMP levels in primary monolayer cultures of epithelial cells prepared from mid-pregnant mice are stimulated by prostaglandin E1 and E2. Prostaglandin F1alpha and F2alpha have only a slight effect upon cyclic AMP levels. In the absence of phosphodiesterase inhibitors the rise in cyclic AMP produced by PGE1 is only transient and the levels return to normal within 30 minutes. High concentrations (16 mM) of theophylline are needed to prevent this decline, suggesting that the phosphodiesterase activity of epithelial cells in culture is high. However, theophylline alone produced only a small increase in basal cyclic AMP levels even over a 2-hour period indicating that basal cyclic AMP is turned over more slowly than cyclic AMP produced in response to stimulation with PGE1. Both PGE and PGF synthesis were monitored using radioimmunoassay procedures previously reported. The observed levels were found to decrease as cell density increased and were sensitive to the addition of agents such as collagen and naproxen."} {"id": "PMID:176691", "title": "Heart sarcolemma as a dynamic excitable membrane.", "content": "Sarcolemma consists of plasma and basement membranes and constitutes the real permeability barrier to the heart cell. It is considered to provide high electrical resistance and capacitance to heart cell and its properties are essentially similar to those of the other excitable membranes. Methods are now available for isolating heart sarcolemma with high specific activities of adenylate cyclase, (Na(+)-K(+) ATPase, Ca(++) ATPase, and Mg(++) APTase. These enzymes are considered to play an important role in heart function by regulating ion movements across sarcolemma as well as by providing signals for various metabolic processes. Sarcolemma possesses different hormone and drug receptors and any alteration in its composition could result in abnormal responses of the myocardium. We believe that heart failure is associated with sarcolemmal defects which can be detected by monitoring the activities of different membrane-bound enzymes and other related processes.", "contents": "Heart sarcolemma as a dynamic excitable membrane. Sarcolemma consists of plasma and basement membranes and constitutes the real permeability barrier to the heart cell. It is considered to provide high electrical resistance and capacitance to heart cell and its properties are essentially similar to those of the other excitable membranes. Methods are now available for isolating heart sarcolemma with high specific activities of adenylate cyclase, (Na(+)-K(+) ATPase, Ca(++) ATPase, and Mg(++) APTase. These enzymes are considered to play an important role in heart function by regulating ion movements across sarcolemma as well as by providing signals for various metabolic processes. Sarcolemma possesses different hormone and drug receptors and any alteration in its composition could result in abnormal responses of the myocardium. We believe that heart failure is associated with sarcolemmal defects which can be detected by monitoring the activities of different membrane-bound enzymes and other related processes."} {"id": "PMID:176692", "title": "Biochemical properties of cardiac sarcolemma: adenylate cyclase and (Na++K+)-activated ATPase.", "content": "Morphologically intact plasma membranes from guinea pig ventricles were obtained by exposing isolated cell segments to osmotic shock, followed by extraction of actomyosin in 1 M KC1. These preparations contained approximately 1/6 of the protein and 5-10 percent of the mitochondrial markers present in the original cell preparation. Both adenylate cyclase and (Na++K+)-activated ATPase activities were enriched 3-4 fold. The receptor for epinephrine stimulation of adenylate cyclase was retained. The \"basal\" ATPase activity of 5-6 mumoles of Pi/mg/hr, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1+20 mM KC1. This increment, the (Na++K+)-activated ATPase, was abolished by 10(-5) M ouabain, the Ki for ouabain being approximately 3x10(-7) M. Adenylate cyclase, which had a basal activity of approximately 0.33 nmole of cyclic AMP produced/min/mg of protein, was significantly stimulated by both l-epinephrine and NaF. Half-maximal stimulation was seen at approximately 5x10(-6) M l-epinephrine. Increasing Ca2+ in the range between 10(-7) and 10(-3) M inhibited basal, l-epinephrine-, and NaF-stimulated adenylate cyclase activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was l-epinephrine-stimulated adenylate cyclase activity, so that l-epinephrine stimulation was increased from approximately 60 percent in 0.5 mM ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid to approximately 150 percent in 10(-7)M Ca2+ and 400 percent in 10(-5) M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feedback mechanism by which eelevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.", "contents": "Biochemical properties of cardiac sarcolemma: adenylate cyclase and (Na++K+)-activated ATPase. Morphologically intact plasma membranes from guinea pig ventricles were obtained by exposing isolated cell segments to osmotic shock, followed by extraction of actomyosin in 1 M KC1. These preparations contained approximately 1/6 of the protein and 5-10 percent of the mitochondrial markers present in the original cell preparation. Both adenylate cyclase and (Na++K+)-activated ATPase activities were enriched 3-4 fold. The receptor for epinephrine stimulation of adenylate cyclase was retained. The \"basal\" ATPase activity of 5-6 mumoles of Pi/mg/hr, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1+20 mM KC1. This increment, the (Na++K+)-activated ATPase, was abolished by 10(-5) M ouabain, the Ki for ouabain being approximately 3x10(-7) M. Adenylate cyclase, which had a basal activity of approximately 0.33 nmole of cyclic AMP produced/min/mg of protein, was significantly stimulated by both l-epinephrine and NaF. Half-maximal stimulation was seen at approximately 5x10(-6) M l-epinephrine. Increasing Ca2+ in the range between 10(-7) and 10(-3) M inhibited basal, l-epinephrine-, and NaF-stimulated adenylate cyclase activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was l-epinephrine-stimulated adenylate cyclase activity, so that l-epinephrine stimulation was increased from approximately 60 percent in 0.5 mM ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid to approximately 150 percent in 10(-7)M Ca2+ and 400 percent in 10(-5) M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feedback mechanism by which eelevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium."} {"id": "PMID:176693", "title": "Adenylate cyclase and catecholamine binding in plasma membrane-enriched preparations of cardiac and skeletal muscle.", "content": "Binding of [3H] epinephrine to plasma membrane-enriched fractions from guinea pig heart and rabbit skeletal muscle was investigated using the micropore filtration technique. [3H] Epinephrine and [3H] norepinephrine were found to be degraded rapidly in aqueous buffer at pH 7.6 and 37 degrees C. Deterioration of the compounds could be prevented by low concentrations of dithiothreitol. Binding of [3H] epinephrine to both membrane preparations was a slow process requiring 60 min to approach equilibrium in the case of cardiac membranes at 37 degrees C, and 20 min for skeletal muscle membranes at 0 degrees C. Binding was antagonized by the unlabeled beta agonists, isopropylnorepinephrine, epinephrine, and nor epinephrine; each was equipotent, in contrast to their different potency is eliciting beta-adrenergic responses and in stimulating adenylate cyclase. A variety of catechol compounds were as effective as antagonists of binding as the catecholamines. Methylation of one ring hydroxyl abolished inhibitory activity. The beta-adrenergic antagonists, propranolol, pronethalol, and dichlorisoproterenol, were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equieffective in antagonizing binding of [3H] norepinephrine to skeletal muscle membranes, suggesting that binding was not stereospecific. These and other data led to the conclusion that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique probably does not reflect interaction with the specific beta-adrenergic recptor, but more likely reflects a less specific binding of compounds with one or more hydroxyl groups on a ring.", "contents": "Adenylate cyclase and catecholamine binding in plasma membrane-enriched preparations of cardiac and skeletal muscle. Binding of [3H] epinephrine to plasma membrane-enriched fractions from guinea pig heart and rabbit skeletal muscle was investigated using the micropore filtration technique. [3H] Epinephrine and [3H] norepinephrine were found to be degraded rapidly in aqueous buffer at pH 7.6 and 37 degrees C. Deterioration of the compounds could be prevented by low concentrations of dithiothreitol. Binding of [3H] epinephrine to both membrane preparations was a slow process requiring 60 min to approach equilibrium in the case of cardiac membranes at 37 degrees C, and 20 min for skeletal muscle membranes at 0 degrees C. Binding was antagonized by the unlabeled beta agonists, isopropylnorepinephrine, epinephrine, and nor epinephrine; each was equipotent, in contrast to their different potency is eliciting beta-adrenergic responses and in stimulating adenylate cyclase. A variety of catechol compounds were as effective as antagonists of binding as the catecholamines. Methylation of one ring hydroxyl abolished inhibitory activity. The beta-adrenergic antagonists, propranolol, pronethalol, and dichlorisoproterenol, were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equieffective in antagonizing binding of [3H] norepinephrine to skeletal muscle membranes, suggesting that binding was not stereospecific. These and other data led to the conclusion that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique probably does not reflect interaction with the specific beta-adrenergic recptor, but more likely reflects a less specific binding of compounds with one or more hydroxyl groups on a ring."} {"id": "PMID:176694", "title": "Adenylate cyclase, cyclic nucleotide phosphodiesterase, and norepinephrine binding in rat heart membranes.", "content": "The method of Kidwai et al. (1971. Biochem. Biophys. Res. Commun. 45:901) offers a rapid and simple technique for the preparation of membrane fractions from rat heart, using sucrose density centrifugation of a 100,000x g pellet. We have investigated the distribution of adenylate cyclase, cyclic AMP phosphodiesterase, and norepinephrine binding activity in these fractions. Specific activity of adenylate cyclase was high in the plasma membrane (PM) and sarcoplasmic reticulum, as well as the nuclear (N) fractions, but 80-90 percent of the total activity was found in the N fraction. Epinephrine stimulation of adenylate cyclase was present in all fractions but did not exceed 25 percent of basal activity. The activity in the mitochondrial fraction was low and insensitive to epinephrine. About 10 percent of phosphodiesterase activity was found in the 100,000 x g pellet. After density gradient centrifugation, 70 percent of this portion was recovered in the N fraction, with the highest specific activity present in the PM fraction. Binding of [3H] norepinephrine was measured by a membrane filtration technique. Binding activity was found in all fractions, and it paralleled roughly the distribution of adenylate cyclase. However, only about 25-30 percent of the binding was blocked by propranolol, except in the PM fraction where binding was not prevented by this drug. Further, a comparison of adenylate cyclase activities with norepinephrine binding yields a turnover number for the enzyme of the order of 10(-2) sec-1, assuming a 1:1 relationship between beta-adrenergic recptor and adenylate cyclase. Since this value seems unrealistic, we suspect that either the binding activity measured is unrelated to the beta-adrenergic receptor or the receptor to cyclase ratio is considerably larger than unity.", "contents": "Adenylate cyclase, cyclic nucleotide phosphodiesterase, and norepinephrine binding in rat heart membranes. The method of Kidwai et al. (1971. Biochem. Biophys. Res. Commun. 45:901) offers a rapid and simple technique for the preparation of membrane fractions from rat heart, using sucrose density centrifugation of a 100,000x g pellet. We have investigated the distribution of adenylate cyclase, cyclic AMP phosphodiesterase, and norepinephrine binding activity in these fractions. Specific activity of adenylate cyclase was high in the plasma membrane (PM) and sarcoplasmic reticulum, as well as the nuclear (N) fractions, but 80-90 percent of the total activity was found in the N fraction. Epinephrine stimulation of adenylate cyclase was present in all fractions but did not exceed 25 percent of basal activity. The activity in the mitochondrial fraction was low and insensitive to epinephrine. About 10 percent of phosphodiesterase activity was found in the 100,000 x g pellet. After density gradient centrifugation, 70 percent of this portion was recovered in the N fraction, with the highest specific activity present in the PM fraction. Binding of [3H] norepinephrine was measured by a membrane filtration technique. Binding activity was found in all fractions, and it paralleled roughly the distribution of adenylate cyclase. However, only about 25-30 percent of the binding was blocked by propranolol, except in the PM fraction where binding was not prevented by this drug. Further, a comparison of adenylate cyclase activities with norepinephrine binding yields a turnover number for the enzyme of the order of 10(-2) sec-1, assuming a 1:1 relationship between beta-adrenergic recptor and adenylate cyclase. Since this value seems unrealistic, we suspect that either the binding activity measured is unrelated to the beta-adrenergic receptor or the receptor to cyclase ratio is considerably larger than unity."} {"id": "PMID:176695", "title": "Influence of thyroid state on the specific binding of noradrenaline to a cardiac particulate fraction and on catecholamine-sensitive cardiac adenylate cyclase activity.", "content": "Specific binding of [3H] noradrenaline, possibly to beta-adrenoreceptors, and adrenaline-sensitive adenylate cyclase activity were measured in particulate preparations from the myocardium of hypothyroid, euthyroid, and hyperthyroid rats. Noradrenaline affinity to the binding sites was decreased and the dose-response curve for the stimulation of adenylate cyclase activity by adrenaline was shifted to the right in hypothyroidism. The opposite changes (an increase in noradrenaline affinity and a shift in the adrenaline-adenylate cyclase dose-response curve to the left) were associated with the hyperthyroid state. These findings correlate well with the result of numerous studies according to which thyroid hormone increases and thyroid hormone deprivation decreases the sensitivity of the myocardium to cardiac sympathetic stimulation and circulating catecholamines.", "contents": "Influence of thyroid state on the specific binding of noradrenaline to a cardiac particulate fraction and on catecholamine-sensitive cardiac adenylate cyclase activity. Specific binding of [3H] noradrenaline, possibly to beta-adrenoreceptors, and adrenaline-sensitive adenylate cyclase activity were measured in particulate preparations from the myocardium of hypothyroid, euthyroid, and hyperthyroid rats. Noradrenaline affinity to the binding sites was decreased and the dose-response curve for the stimulation of adenylate cyclase activity by adrenaline was shifted to the right in hypothyroidism. The opposite changes (an increase in noradrenaline affinity and a shift in the adrenaline-adenylate cyclase dose-response curve to the left) were associated with the hyperthyroid state. These findings correlate well with the result of numerous studies according to which thyroid hormone increases and thyroid hormone deprivation decreases the sensitivity of the myocardium to cardiac sympathetic stimulation and circulating catecholamines."} {"id": "PMID:176696", "title": "Epinephrine, cyclic AMP, calcium, and myocardial contractility.", "content": "In the first part of this paper, a short review of the literature on the effects of catecholamines, Ca2+, and cyclic AMP on the biochemical, electrical, and mechanical properties of the heart is presented. It is concluded that the effects of epinephrine on activation of glycogenolysis and on the inotropic response of cardiac muscle are both mediated by the combined actions of Ca2+ and cyclic AMP. Since the inotropic response precedes the glycogenolytic response it is evident that increased energy metabolism is a consequence of increased heart work and not a causative factor. The available data suggest that increased tissue cyclic AMP levels resulting from catecholamine stimulation of adenyl cyclase activity alter cardiac mechanics by modulation of the basic calcium flux cycle of the heart. These effects may be mediated by cyclic AMP-stimulated phosphorylation of specific proteins located in the sarcolemma, sarcoplasmic reticulum, and myofilaments via one or more protein kinases, although experimental verfication of the possible relationship between protein phosphorylation and altered Ca2+ binding properties at specific sites in the membranes is at present largely lacking. The increased rate of tension development induced by catecholamines appears to be caused by an increased rate of Ca2+ influx across the sarcolemma during the plateau phase of the action potential, whereas the increased rate of relaxation is probably attributable to an increased rate of sequestration of intracellular Ca2+ by the sarcoplasmic reticulum. In the second part of the paper, data are presented using a working rat heart preparation to illustrate the effect of catecholamines in facilitating Ca2+ entry across the sarcolemma. Decreased left ventricular pressure development induced by addition of ruthenium red or verapamil to inhibit Ca2+ influx was relieved in a concentration-dependent manner by catecholamines. Curves of percentage change of left ventricular pressure against external Ca2+ concentration are presented which show that epinephrine increased the sensitivity of the heart to Ca2+ whereas verapamil decreased it. A half-maximal increase of left ventricular pressure was obtained with 0.6 mM Ca2+ in control hearts, 0.3 mM Ca2+ with epinephrine, and 2.9 mM Ca2+ with verapamil (10(-7)-treated hearts. Verapamil combined with epinephrine at the above concentrations gave a half-miximal increase of left ventricular pressure with 1.3 mM Ca2+. These results are discussed in relation to a model for the Ca2+ flux in the heart.", "contents": "Epinephrine, cyclic AMP, calcium, and myocardial contractility. In the first part of this paper, a short review of the literature on the effects of catecholamines, Ca2+, and cyclic AMP on the biochemical, electrical, and mechanical properties of the heart is presented. It is concluded that the effects of epinephrine on activation of glycogenolysis and on the inotropic response of cardiac muscle are both mediated by the combined actions of Ca2+ and cyclic AMP. Since the inotropic response precedes the glycogenolytic response it is evident that increased energy metabolism is a consequence of increased heart work and not a causative factor. The available data suggest that increased tissue cyclic AMP levels resulting from catecholamine stimulation of adenyl cyclase activity alter cardiac mechanics by modulation of the basic calcium flux cycle of the heart. These effects may be mediated by cyclic AMP-stimulated phosphorylation of specific proteins located in the sarcolemma, sarcoplasmic reticulum, and myofilaments via one or more protein kinases, although experimental verfication of the possible relationship between protein phosphorylation and altered Ca2+ binding properties at specific sites in the membranes is at present largely lacking. The increased rate of tension development induced by catecholamines appears to be caused by an increased rate of Ca2+ influx across the sarcolemma during the plateau phase of the action potential, whereas the increased rate of relaxation is probably attributable to an increased rate of sequestration of intracellular Ca2+ by the sarcoplasmic reticulum. In the second part of the paper, data are presented using a working rat heart preparation to illustrate the effect of catecholamines in facilitating Ca2+ entry across the sarcolemma. Decreased left ventricular pressure development induced by addition of ruthenium red or verapamil to inhibit Ca2+ influx was relieved in a concentration-dependent manner by catecholamines. Curves of percentage change of left ventricular pressure against external Ca2+ concentration are presented which show that epinephrine increased the sensitivity of the heart to Ca2+ whereas verapamil decreased it. A half-maximal increase of left ventricular pressure was obtained with 0.6 mM Ca2+ in control hearts, 0.3 mM Ca2+ with epinephrine, and 2.9 mM Ca2+ with verapamil (10(-7)-treated hearts. Verapamil combined with epinephrine at the above concentrations gave a half-miximal increase of left ventricular pressure with 1.3 mM Ca2+. These results are discussed in relation to a model for the Ca2+ flux in the heart."} {"id": "PMID:176697", "title": "Regulation of calcium transport in cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase.", "content": "A manyfold increase in phosphorylation of cardiac sarcoplasmic reticulum (SR) was seen when SR was incubated in the presence of a bovine cardiac cyclic AMP-dependent protein kinase and cyclic AMP. This phosphoprotein had stability characteristics of a phosphoester in which the phosphate is incorporated largely into serine, and its formation did not required calcium ions, unlike the formation of acyl phosphoprotein intermediate of calcium-transport ATPase which is present within the same membrane. When examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein kinase-catalyzed phosphorylation occurred at a 22,000-dalton component of the cardiac sarcoplasmic reticulum. This 22,000-dalton protein has been named \"phospholamban\" (lambda alpha mu beta alpha nu epsilon iota nu = to receive), based on its ability to receive phosphate from ATP. Phosphorylation of phospholamban by cyclic AMP-dependent protein kinase was associated with the stimulation of calcium transport by the cardiac sarcoplasmic reticulum. This stimulation was accompanied by an increase in the calcium-activated ATPase activity, indicating that the overall rate of calcium transport rather than its efficiency is enhanced by protein kinase. The 22,000-dalton phopholamban was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose prevented subsequent phosphorylation of phospholamban, while leaving the calcium pump apparently intact. Incubation of trypsin-treated sarcoplasmic reticulum with cyclic AMP-depentent protein kinase did not result in the stimulation of calcium transport. These results may suggest that phospholamban is a modulator of the calcium pump of the cardiac sarcoplasmic reticulum.", "contents": "Regulation of calcium transport in cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase. A manyfold increase in phosphorylation of cardiac sarcoplasmic reticulum (SR) was seen when SR was incubated in the presence of a bovine cardiac cyclic AMP-dependent protein kinase and cyclic AMP. This phosphoprotein had stability characteristics of a phosphoester in which the phosphate is incorporated largely into serine, and its formation did not required calcium ions, unlike the formation of acyl phosphoprotein intermediate of calcium-transport ATPase which is present within the same membrane. When examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein kinase-catalyzed phosphorylation occurred at a 22,000-dalton component of the cardiac sarcoplasmic reticulum. This 22,000-dalton protein has been named \"phospholamban\" (lambda alpha mu beta alpha nu epsilon iota nu = to receive), based on its ability to receive phosphate from ATP. Phosphorylation of phospholamban by cyclic AMP-dependent protein kinase was associated with the stimulation of calcium transport by the cardiac sarcoplasmic reticulum. This stimulation was accompanied by an increase in the calcium-activated ATPase activity, indicating that the overall rate of calcium transport rather than its efficiency is enhanced by protein kinase. The 22,000-dalton phopholamban was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose prevented subsequent phosphorylation of phospholamban, while leaving the calcium pump apparently intact. Incubation of trypsin-treated sarcoplasmic reticulum with cyclic AMP-depentent protein kinase did not result in the stimulation of calcium transport. These results may suggest that phospholamban is a modulator of the calcium pump of the cardiac sarcoplasmic reticulum."} {"id": "PMID:176698", "title": "Increased Ca2+ binding by a cardiac cell membrane preparation after cyclic AMP-enhanced intrinsic membrane protein phosphorylation.", "content": "Ca2+ binding to a sarcolemma-enriched membrane fraction from pig myocardium possessing an intrinsic cyclic AMP-dependent protein kinase occurs at several classes of low affinity binding sites and at two high affinity binding sites with binding constants of about 1.5-1.7x10(7) M-1 (0.3 nmole of Ca2+/mg protein) and 0.9-2.9x10(6) M-1 (0.8 nmole of Ca2+/mg protein). Ca2+ binding properties are not affected by verapamil and ouabain, whereas ruthenium red depresses Ca2+ binding at the low affinity binding sites and La3+ ions strongly reduce both low and high affinity Ca2+ binding. A profound inhibition of the high affinity Ca2+ binding sites was observed in the presence of Na+ ions, half-maximal inhibition at a free Ca2+ concentration of 2x10(-8) M being achieved by 11 mM NaC1. High affinity Ca2+ binding is also diminished after pretreatment of the membranes with trypsin and phospholipase A. Phosphorylation of one or two of the membrane proteins by the endogenous cyclic AMP-dependent protein kinase leads at both classes of high affinity Ca2+ binding sites to an approximately 4-fold increase in affinity, the number of these sites remaining unchanged. The high affinity Ca2+ binding sites may possibly be involved in Ca2+ extrusion from the cell and in the relaxation process.", "contents": "Increased Ca2+ binding by a cardiac cell membrane preparation after cyclic AMP-enhanced intrinsic membrane protein phosphorylation. Ca2+ binding to a sarcolemma-enriched membrane fraction from pig myocardium possessing an intrinsic cyclic AMP-dependent protein kinase occurs at several classes of low affinity binding sites and at two high affinity binding sites with binding constants of about 1.5-1.7x10(7) M-1 (0.3 nmole of Ca2+/mg protein) and 0.9-2.9x10(6) M-1 (0.8 nmole of Ca2+/mg protein). Ca2+ binding properties are not affected by verapamil and ouabain, whereas ruthenium red depresses Ca2+ binding at the low affinity binding sites and La3+ ions strongly reduce both low and high affinity Ca2+ binding. A profound inhibition of the high affinity Ca2+ binding sites was observed in the presence of Na+ ions, half-maximal inhibition at a free Ca2+ concentration of 2x10(-8) M being achieved by 11 mM NaC1. High affinity Ca2+ binding is also diminished after pretreatment of the membranes with trypsin and phospholipase A. Phosphorylation of one or two of the membrane proteins by the endogenous cyclic AMP-dependent protein kinase leads at both classes of high affinity Ca2+ binding sites to an approximately 4-fold increase in affinity, the number of these sites remaining unchanged. The high affinity Ca2+ binding sites may possibly be involved in Ca2+ extrusion from the cell and in the relaxation process."} {"id": "PMID:176699", "title": "Effects of glucagon on cardiac cyclic nucleotides in the hypoxic heart.", "content": "Isolated rat hearts were perfused with a subinotropic concentration of glucagon during an hypoxic perfusion to determine whether glucagon would enhance recovery upon reoxygenation. Rat hearts were divided into two groups: 1) those perfused with glucose-free Tyrode's solution and 2) those perfused with Tyrode's solution containing glucose. During 3 min of hypoxic exposure, untreated hearts and hearts perfused with glucagon both demonstrated a dramatic decrease in contractile force regardless of whether glucose was included in the medium. However, when glucose was present in the perfusion medium cardiac performance was better during both hypoxia and the period of reoxygenation. Furthermore, during reoxygenation, the recovery of contractile force was significantly greater in glucagon-perfused hearts than in controls. Cardiac levels of cyclic AMP and cyclic GMP were monitored at various periods of hypoxic exposure to test the existence of a correlation between the concentrations of these cyclic nucleotides and cardiac performance. During reoxygenation of untreated hearts, the hearts perfused with glucose-free medium attained 45-50 percent of the contractile force seen in glucagon-treated hearts. This enhanced recovery in the glucagon-treated hearts was associated with decreases in cyclic GMP levels at the end of the hypoxic period. At this time, the cyclic GMP levels in the glucagon-treated hearts were only 25-55 percent of the levels seen in untreated hearts that were also exposed to hypoxia. The effect of glucagon on cyclic AMP content in untreated hearts and in hearts receiving glucagon was not significantly different at 3 min of hypoxia. These studies suggest that subinotropic concentrations of glucagon exert a protective effect on the hypoxic rat heart that is not related to the direct inotropic properties of this hormone but which may involve a modulation in cardiac cyclic GMP availability.", "contents": "Effects of glucagon on cardiac cyclic nucleotides in the hypoxic heart. Isolated rat hearts were perfused with a subinotropic concentration of glucagon during an hypoxic perfusion to determine whether glucagon would enhance recovery upon reoxygenation. Rat hearts were divided into two groups: 1) those perfused with glucose-free Tyrode's solution and 2) those perfused with Tyrode's solution containing glucose. During 3 min of hypoxic exposure, untreated hearts and hearts perfused with glucagon both demonstrated a dramatic decrease in contractile force regardless of whether glucose was included in the medium. However, when glucose was present in the perfusion medium cardiac performance was better during both hypoxia and the period of reoxygenation. Furthermore, during reoxygenation, the recovery of contractile force was significantly greater in glucagon-perfused hearts than in controls. Cardiac levels of cyclic AMP and cyclic GMP were monitored at various periods of hypoxic exposure to test the existence of a correlation between the concentrations of these cyclic nucleotides and cardiac performance. During reoxygenation of untreated hearts, the hearts perfused with glucose-free medium attained 45-50 percent of the contractile force seen in glucagon-treated hearts. This enhanced recovery in the glucagon-treated hearts was associated with decreases in cyclic GMP levels at the end of the hypoxic period. At this time, the cyclic GMP levels in the glucagon-treated hearts were only 25-55 percent of the levels seen in untreated hearts that were also exposed to hypoxia. The effect of glucagon on cyclic AMP content in untreated hearts and in hearts receiving glucagon was not significantly different at 3 min of hypoxia. These studies suggest that subinotropic concentrations of glucagon exert a protective effect on the hypoxic rat heart that is not related to the direct inotropic properties of this hormone but which may involve a modulation in cardiac cyclic GMP availability."} {"id": "PMID:176700", "title": "Drug-induced changes in the superficially located stores of calcium in heart sarcolemma.", "content": "Excitation-contraction coupling in heart muscle cells depends upon an inward displacement of Ca2+ from the extra- to the intracellular phase. Some of the Ca2+ which is displaced inwards is probably derived from superficially located binding sites. Drugs which increase the peak tension developed during contraction, e.g., catecholamines and the cardiac glycosides, may act by increasing the amount of Ca2+ which becomes available for participation in the events associated with excitation-contraction coupling. The catecholamines increase in the amount of Ca2+ which is displaced inward from the extracellular phase, whereas the cardiac glycosides apparently act by increasing the exchangeability of the Ca2+ which is stored at binding sites located at the plasma membrane. Other drugs, e.g., verapamil, act in the reverse manner, decreasing the amount of Ca2+ which is available for displacement from the superficially located binding sites. These observations will be discussed in terms of an hypothesis that the plasma membrane represents an important site of drug action, and that many drugs which alter the contractile performance of the heart do so because of their ability to modify the ability of the plasma membrane to accumulate and exchange Ca2+.", "contents": "Drug-induced changes in the superficially located stores of calcium in heart sarcolemma. Excitation-contraction coupling in heart muscle cells depends upon an inward displacement of Ca2+ from the extra- to the intracellular phase. Some of the Ca2+ which is displaced inwards is probably derived from superficially located binding sites. Drugs which increase the peak tension developed during contraction, e.g., catecholamines and the cardiac glycosides, may act by increasing the amount of Ca2+ which becomes available for participation in the events associated with excitation-contraction coupling. The catecholamines increase in the amount of Ca2+ which is displaced inward from the extracellular phase, whereas the cardiac glycosides apparently act by increasing the exchangeability of the Ca2+ which is stored at binding sites located at the plasma membrane. Other drugs, e.g., verapamil, act in the reverse manner, decreasing the amount of Ca2+ which is available for displacement from the superficially located binding sites. These observations will be discussed in terms of an hypothesis that the plasma membrane represents an important site of drug action, and that many drugs which alter the contractile performance of the heart do so because of their ability to modify the ability of the plasma membrane to accumulate and exchange Ca2+."} {"id": "PMID:176705", "title": "The effect of histamine, isoproterenol and tyramine on rat uterine cyclic AMP.", "content": "Isoproterenol (10(-4) M), histamine (10(-3) M) and tyramine (10(-3) M) elevated cyclic AMP levels in incubated rat urerine segments. Promethazine (10(-6) M) an H1-receptor antagonist was ineffective in blocking the increase in cyclic AMP due to isoproterenol, histamine and tyramine. Buriamide (10(-6) M), an H2 receptor antagonist, was effective in almost abolishing the cyclic AMP elevation due to histamine, whereas burimamide did not affect the cyclic AMP levels elevated by tyramine and only slightly reduced the isoproterenol response. Propranolol was effective in reducing or abolishing the cyclic AMP accumulation by all three agonists. The respective blockade by burimamide or propranolol was overcome by increasing the concentration of the agonists. Histamine (10(-3) M) and tyramine (10(-3) M) failed to elevate cyclic AMP in uterine segments obtained from reserpine treated rats. The data supports the hypothesis that histamine, like tyramine, has an indirect effect on the rat uterus mediated through the release of endogenous norepinephrine.", "contents": "The effect of histamine, isoproterenol and tyramine on rat uterine cyclic AMP. Isoproterenol (10(-4) M), histamine (10(-3) M) and tyramine (10(-3) M) elevated cyclic AMP levels in incubated rat urerine segments. Promethazine (10(-6) M) an H1-receptor antagonist was ineffective in blocking the increase in cyclic AMP due to isoproterenol, histamine and tyramine. Buriamide (10(-6) M), an H2 receptor antagonist, was effective in almost abolishing the cyclic AMP elevation due to histamine, whereas burimamide did not affect the cyclic AMP levels elevated by tyramine and only slightly reduced the isoproterenol response. Propranolol was effective in reducing or abolishing the cyclic AMP accumulation by all three agonists. The respective blockade by burimamide or propranolol was overcome by increasing the concentration of the agonists. Histamine (10(-3) M) and tyramine (10(-3) M) failed to elevate cyclic AMP in uterine segments obtained from reserpine treated rats. The data supports the hypothesis that histamine, like tyramine, has an indirect effect on the rat uterus mediated through the release of endogenous norepinephrine."} {"id": "PMID:176706", "title": "Phosphodiesterase inhibition and lipolytic action of the stereoisomers of trimetoquinol.", "content": "The isomers and racemate of trimetoquinol [TMQ; 6-7-dihydroxy-1-(3',4',5'-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] as well as N-(3',4',5'-trimethoxyphenethyl)dopamine were all shown to be effective at promoting glycerol release from rat epididymal fat tissue. The rank order of potency observed for these compounds was (-)-TMQ greater than or equal to (+/-)-TMQ greater than greater than (+)-TMQ = N-(3',4',5-trimethoxyphenethyl)dopamine. (+/-)-TMQ and (-)-TMQ were the only agents capable of producing a maximal lipolytic response. None of the compounds tested were able to exhibit significant c-AMP phosphodiesterase inhibition. This study is the first report which shows that the beta-adrenoceptor activity of the isomers of TMQ does not correlate with an inhibition of c-AMP phosphodiesterase. An alternate mechanism of action for these compounds is proposed.", "contents": "Phosphodiesterase inhibition and lipolytic action of the stereoisomers of trimetoquinol. The isomers and racemate of trimetoquinol [TMQ; 6-7-dihydroxy-1-(3',4',5'-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] as well as N-(3',4',5'-trimethoxyphenethyl)dopamine were all shown to be effective at promoting glycerol release from rat epididymal fat tissue. The rank order of potency observed for these compounds was (-)-TMQ greater than or equal to (+/-)-TMQ greater than greater than (+)-TMQ = N-(3',4',5-trimethoxyphenethyl)dopamine. (+/-)-TMQ and (-)-TMQ were the only agents capable of producing a maximal lipolytic response. None of the compounds tested were able to exhibit significant c-AMP phosphodiesterase inhibition. This study is the first report which shows that the beta-adrenoceptor activity of the isomers of TMQ does not correlate with an inhibition of c-AMP phosphodiesterase. An alternate mechanism of action for these compounds is proposed."} {"id": "PMID:176707", "title": "Infectious bovine rhinotracheitis virus: studies on the venereal carrier status in range cattle.", "content": "Genital samples collected at autopsy from 193 beef cows representing 22 different herds in Northern Australia yielded only one isolate of infectious bovine rhinotracheitis (IBR) virus. Serological evidence showed 59 per cent of similar cows had prior infection with this virus and of 19 sero-positive cows tested, 11 (58-2 per cent) shed detectable IBR virus from the vagina after treatment with corticosteroids. Transitory lesions of the vagina and vulva developed in five of the treated cows. Twenty-six (65 per cent) of 40 sero-positive bulls shed detectable IBR virus into the prepuce after corticosteroid treatment. Except for one bull, virus was not isolated after corticosteroid treatment of sero-negative animals. IBR virus and mucosal disease (MD) virus were not isolated from nasal swabs before or after corticosteroid administration. No correlation was observed between initial circulating antiboyd titre and virus excretion after treatment. There were no significant changes in levels of serum antibody during the virus excretion period.", "contents": "Infectious bovine rhinotracheitis virus: studies on the venereal carrier status in range cattle. Genital samples collected at autopsy from 193 beef cows representing 22 different herds in Northern Australia yielded only one isolate of infectious bovine rhinotracheitis (IBR) virus. Serological evidence showed 59 per cent of similar cows had prior infection with this virus and of 19 sero-positive cows tested, 11 (58-2 per cent) shed detectable IBR virus from the vagina after treatment with corticosteroids. Transitory lesions of the vagina and vulva developed in five of the treated cows. Twenty-six (65 per cent) of 40 sero-positive bulls shed detectable IBR virus into the prepuce after corticosteroid treatment. Except for one bull, virus was not isolated after corticosteroid treatment of sero-negative animals. IBR virus and mucosal disease (MD) virus were not isolated from nasal swabs before or after corticosteroid administration. No correlation was observed between initial circulating antiboyd titre and virus excretion after treatment. There were no significant changes in levels of serum antibody during the virus excretion period."} {"id": "PMID:176715", "title": "Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). I. Isolation and characterization.", "content": "The occurrence on cellulose acetate and agarose gel electrophoresis of additional bands with the mobility of pre-beta-lipoprotein (LP) has recently been linked to ischemic heart disease (IHD). In the present study, one of these additional pre-beta-LP fractions, earlier designated as 'pre-beta-LP' and now defined on agarose gel electrophoresis, was isolated by preparative ultracentrifugation and gel filtration. The characterization of this pre-beta-1-LP revealed a 'sinking pre-beta-LP' (SPB) of density 1.050-1.080 g/ml. SPB shared its major antigenic determinant with low-density lipoproteins (LDL) and resembled closely LDL with regard to its lipid composition. Specific anti-LP(a) serum confirmed the presence of LP(a) antigen in the purified SPB preparation.", "contents": "Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). I. Isolation and characterization. The occurrence on cellulose acetate and agarose gel electrophoresis of additional bands with the mobility of pre-beta-lipoprotein (LP) has recently been linked to ischemic heart disease (IHD). In the present study, one of these additional pre-beta-LP fractions, earlier designated as 'pre-beta-LP' and now defined on agarose gel electrophoresis, was isolated by preparative ultracentrifugation and gel filtration. The characterization of this pre-beta-1-LP revealed a 'sinking pre-beta-LP' (SPB) of density 1.050-1.080 g/ml. SPB shared its major antigenic determinant with low-density lipoproteins (LDL) and resembled closely LDL with regard to its lipid composition. Specific anti-LP(a) serum confirmed the presence of LP(a) antigen in the purified SPB preparation."} {"id": "PMID:176716", "title": "Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). II. Fatty acid composition of lipid moieties.", "content": "The appearance of additional lipoprotein fractions with pre-beta-mobility on cellulose acetate and agarose gel electrophoresis has recently been linked with the early occurrence of ischemic heart disease (IHD). One of these fractions, designated sinking pre-beta-lipoprotein (SPB) has been isolated, purified, and identififed as synonymous with LP(a). In the present study, the lipid moieties of this lipoprotein fraction were further characterized as to their fatty acid composition. These were almost identical to those of low-density lipoprotein (LDL) lipid moieties. The acute influence on fatty acid composition of SPB lipid moieties, 5 hr after a linoleic acid-rich test meal, was a 40% increase in triglyceride linoleic acid content and only minor changes in phosphoglyceride fatty acids. Data speak against an actual conversion of chylomicron remnants into SPB but would allow a certain exchange of lipid moiety among chylomicrons, SPB, and LDL. It is therefore suggested that the origin of the SPB presumably synonymous with LP(a) is the same as for LDL: the liver.", "contents": "Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). II. Fatty acid composition of lipid moieties. The appearance of additional lipoprotein fractions with pre-beta-mobility on cellulose acetate and agarose gel electrophoresis has recently been linked with the early occurrence of ischemic heart disease (IHD). One of these fractions, designated sinking pre-beta-lipoprotein (SPB) has been isolated, purified, and identififed as synonymous with LP(a). In the present study, the lipid moieties of this lipoprotein fraction were further characterized as to their fatty acid composition. These were almost identical to those of low-density lipoprotein (LDL) lipid moieties. The acute influence on fatty acid composition of SPB lipid moieties, 5 hr after a linoleic acid-rich test meal, was a 40% increase in triglyceride linoleic acid content and only minor changes in phosphoglyceride fatty acids. Data speak against an actual conversion of chylomicron remnants into SPB but would allow a certain exchange of lipid moiety among chylomicrons, SPB, and LDL. It is therefore suggested that the origin of the SPB presumably synonymous with LP(a) is the same as for LDL: the liver."} {"id": "PMID:176717", "title": "Studies on human serum high-density lipoproteins. V. Isolation and characterization of a cholesterol ester-rich lipoprotein after in vitro incubation.", "content": "Purified high-density lipoprotein (HDL), obtained by preparative ultracentrifugation at density 1.063-1.19 g/ml in the cold, were subfractionated by hydroxyl apatite column chromatography. Two of the obtained subfractions (subfractions II and III) turned turbid after incubation at 37 degrees C for 12 h. The turbid material was recovered in the supernatant of D 1.006 g/ml after centriguation at 30,000 g for 2 h. The lipoprotein fraction causing the turbidity was composed of 94% cholesterol ester and 2% apolipoprotein (by weight). On polyacrylamide gel electrophoresis the apolipoprotein moiety appeared as one polypeptide with the electrophoretic mobility of polypeptide A-I, revealed a blocked NH2-terminal amino acid, and had a total amino acid composition that differed from that of A-I and of the arginine-rich polypeptide.", "contents": "Studies on human serum high-density lipoproteins. V. Isolation and characterization of a cholesterol ester-rich lipoprotein after in vitro incubation. Purified high-density lipoprotein (HDL), obtained by preparative ultracentrifugation at density 1.063-1.19 g/ml in the cold, were subfractionated by hydroxyl apatite column chromatography. Two of the obtained subfractions (subfractions II and III) turned turbid after incubation at 37 degrees C for 12 h. The turbid material was recovered in the supernatant of D 1.006 g/ml after centriguation at 30,000 g for 2 h. The lipoprotein fraction causing the turbidity was composed of 94% cholesterol ester and 2% apolipoprotein (by weight). On polyacrylamide gel electrophoresis the apolipoprotein moiety appeared as one polypeptide with the electrophoretic mobility of polypeptide A-I, revealed a blocked NH2-terminal amino acid, and had a total amino acid composition that differed from that of A-I and of the arginine-rich polypeptide."} {"id": "PMID:176718", "title": "Serum beta-lipoprotein subfractions in polyacrylamide gel electrophoresis associated with coronary heart disease.", "content": "Subfractions of beta-lipoprotein occurred more frequently in serum from patients with coronary heart disease than in serum from patients with no sign of coronary heart disease. Two beta-lipoprotein subfractions were observed in polyacrylamide gel electrophoresis. The sera containing a beta-lipoprotein subfraction with a position close to the beta-lipoprotein band showed Lp(a) antigenic properties. Triglycerides were raised in the sera with beta-lipoprotein subfractions. The cholesterol level was significantly higher in the coronary heart disease group but was not correlated to the presence of the beta-lipoprotein subfraction. The beta-lipoprotein subfraction may possibly represent an additional risk factor in the genesis of coronary heart disease, even in the absence of other hyperlipoproteinemias.", "contents": "Serum beta-lipoprotein subfractions in polyacrylamide gel electrophoresis associated with coronary heart disease. Subfractions of beta-lipoprotein occurred more frequently in serum from patients with coronary heart disease than in serum from patients with no sign of coronary heart disease. Two beta-lipoprotein subfractions were observed in polyacrylamide gel electrophoresis. The sera containing a beta-lipoprotein subfraction with a position close to the beta-lipoprotein band showed Lp(a) antigenic properties. Triglycerides were raised in the sera with beta-lipoprotein subfractions. The cholesterol level was significantly higher in the coronary heart disease group but was not correlated to the presence of the beta-lipoprotein subfraction. The beta-lipoprotein subfraction may possibly represent an additional risk factor in the genesis of coronary heart disease, even in the absence of other hyperlipoproteinemias."} {"id": "PMID:176719", "title": "Histochemical localization of alkaline pyrophosphate- phosphohydrolase in tooth-forming cells of rat.", "content": "The activity of a pyrophosphate-splitting tissue factor in jaws, teeth and intestinal mucosa has been studied by means of histochemistry. Freeze-cut, unfixed sections of whole animals were incubated in a buffered medium (pH 8.6) containing inorganic pyrophosphate (PP) Pb2+, Mg2+, and Zn2+ at various concentrations. The effects of compound R 8231, heat, aldehyde fixation, and demineralization with EDTA were also investigated. In sections showing optimal staining, deposition of incubation products was found in the stratum intermedium and the subodontoblastic cells of the developing tooth, in the osteoblastic layers, and at the surface of the intestinal mucosa. The hard tissues were also stained except in the demineralized sections. Treatment with heat or compound R 8231 resulted in loss of originally observed soft tissue staining while short-time demineralization with EDTA enhanced the staining reaction. It is argued that a nonspecific deposition of the capturing ion, Pb2+, can hardly explain the observed soft tissue staining. The results point to the presence of a PP-splitting enzyme, and it is suggested that the enzyme exhibits features of an alkaline phosphatase with PP-phospholhydrolytic properties rather than of an inorganic pyrophosphatase.", "contents": "Histochemical localization of alkaline pyrophosphate- phosphohydrolase in tooth-forming cells of rat. The activity of a pyrophosphate-splitting tissue factor in jaws, teeth and intestinal mucosa has been studied by means of histochemistry. Freeze-cut, unfixed sections of whole animals were incubated in a buffered medium (pH 8.6) containing inorganic pyrophosphate (PP) Pb2+, Mg2+, and Zn2+ at various concentrations. The effects of compound R 8231, heat, aldehyde fixation, and demineralization with EDTA were also investigated. In sections showing optimal staining, deposition of incubation products was found in the stratum intermedium and the subodontoblastic cells of the developing tooth, in the osteoblastic layers, and at the surface of the intestinal mucosa. The hard tissues were also stained except in the demineralized sections. Treatment with heat or compound R 8231 resulted in loss of originally observed soft tissue staining while short-time demineralization with EDTA enhanced the staining reaction. It is argued that a nonspecific deposition of the capturing ion, Pb2+, can hardly explain the observed soft tissue staining. The results point to the presence of a PP-splitting enzyme, and it is suggested that the enzyme exhibits features of an alkaline phosphatase with PP-phospholhydrolytic properties rather than of an inorganic pyrophosphatase."} {"id": "PMID:176720", "title": "Function of granulocytes with deficient myeloperoxidase-mediated iodination in a patient with generalized pustular psoriasis.", "content": "The granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysosomal enzymes, beta-glucuronidase, N-acetyl-beta-glucosaminidase and lysozyme, were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide- and cyanide-resistant, MPO-independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPP is characterized by the development of subcorneal pustules containing granulocytes, the MPO-deficiency may be the cause of or enhance the development of the disease.", "contents": "Function of granulocytes with deficient myeloperoxidase-mediated iodination in a patient with generalized pustular psoriasis. The granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysosomal enzymes, beta-glucuronidase, N-acetyl-beta-glucosaminidase and lysozyme, were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide- and cyanide-resistant, MPO-independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPP is characterized by the development of subcorneal pustules containing granulocytes, the MPO-deficiency may be the cause of or enhance the development of the disease."} {"id": "PMID:176723", "title": "Magnesium depletion and hypocalcaemia after removal of parathyroid carcinoma.", "content": "A case of parathyroid carcinoma is described which presented with severe bone disease, complicated after parathyroidectomy by symptomatic hypocalcaemia and magnesium deficiency, both of which responded dramatically to the administration of magnesium. Urinary cyclic AMP assays were used to monitor parathyroid activity.", "contents": "Magnesium depletion and hypocalcaemia after removal of parathyroid carcinoma. A case of parathyroid carcinoma is described which presented with severe bone disease, complicated after parathyroidectomy by symptomatic hypocalcaemia and magnesium deficiency, both of which responded dramatically to the administration of magnesium. Urinary cyclic AMP assays were used to monitor parathyroid activity."} {"id": "PMID:176724", "title": "REM sleep induction by physostigmine infusion during sleep.", "content": "Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers. When injected during rapid eye movement (REM) sleep, physostigmine woke the subjects, and when injected during non-REM sleep, it induced REM sleep. This result suggests that cholinergic mechanisms play a role in the induction of REM sleep and in modulating cortical arousal mechanisms.", "contents": "REM sleep induction by physostigmine infusion during sleep. Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers. When injected during rapid eye movement (REM) sleep, physostigmine woke the subjects, and when injected during non-REM sleep, it induced REM sleep. This result suggests that cholinergic mechanisms play a role in the induction of REM sleep and in modulating cortical arousal mechanisms."} {"id": "PMID:176725", "title": "Human glyceraldehyde-3-phosphate dehydrogenase in man-rodent somatic cell hybrids.", "content": "The human enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms heteropolymers with the rodent enzyme in man-rodent somatic cell hybrids. A gene specifying GAPDH is syntenic with the genes specifying the glycolytic enzymes triosephosphate isomerase (TPI) and lactate dehydrogenase B (LDH-B). The synteny of GAPDH, TPI, and LDH-B is the first evidence for the syntenic association of human genes that specify enzymes of the Embden-Meyerhof glycolytic pathway.", "contents": "Human glyceraldehyde-3-phosphate dehydrogenase in man-rodent somatic cell hybrids. The human enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms heteropolymers with the rodent enzyme in man-rodent somatic cell hybrids. A gene specifying GAPDH is syntenic with the genes specifying the glycolytic enzymes triosephosphate isomerase (TPI) and lactate dehydrogenase B (LDH-B). The synteny of GAPDH, TPI, and LDH-B is the first evidence for the syntenic association of human genes that specify enzymes of the Embden-Meyerhof glycolytic pathway."} {"id": "PMID:176726", "title": "Theiler's virus-induced demyelination: prevention by immunosuppression.", "content": "The effect of immunosuppression with cyclophosphamide and rabbit antiserum to mouse thymocytes on demyelination induced by Theiler's virus in SJL/J mice was ascertained from Epon-embedded sections (1 micrometer) of the central nervous system. Immunosuppression not only eliminated mononuclear cell infiltrates in the spinal cord white matter, but it also prevented the occurrence of demyelination. These results suggest that demyelination in this infection is immune-mediated.", "contents": "Theiler's virus-induced demyelination: prevention by immunosuppression. The effect of immunosuppression with cyclophosphamide and rabbit antiserum to mouse thymocytes on demyelination induced by Theiler's virus in SJL/J mice was ascertained from Epon-embedded sections (1 micrometer) of the central nervous system. Immunosuppression not only eliminated mononuclear cell infiltrates in the spinal cord white matter, but it also prevented the occurrence of demyelination. These results suggest that demyelination in this infection is immune-mediated."} {"id": "PMID:176727", "title": "Blockade of prolactin action by an antiserum to its receptors.", "content": "A guinea pig antiserum to prolactin receptors selectively inhibited the binding of [125I] prolactin to its membrane receptors as well as prolactin-mediated incorporation of [3H] leucine into casein and transport of [14C] aminoisobutyric acid, but was without effect on the binding of [125I] insulin and insulin-mediated events in explants of rabbit mammary glands maintained in culture. These findings provide direct evidence for an obligatory functional role of a membrane receptor in mediating the action of a polypeptide hormone.", "contents": "Blockade of prolactin action by an antiserum to its receptors. A guinea pig antiserum to prolactin receptors selectively inhibited the binding of [125I] prolactin to its membrane receptors as well as prolactin-mediated incorporation of [3H] leucine into casein and transport of [14C] aminoisobutyric acid, but was without effect on the binding of [125I] insulin and insulin-mediated events in explants of rabbit mammary glands maintained in culture. These findings provide direct evidence for an obligatory functional role of a membrane receptor in mediating the action of a polypeptide hormone."} {"id": "PMID:176728", "title": "Neurotransmitter regulation of adenosine 3',5'-monophosphate in clonal nerve, glia, and muscle cell lines.", "content": "Norepinephrine increases the intracellular level of adenosine 3',5'-monophosphate (cyclic AMP) in clonal cell lines of nerve, glia, smooth muscel, and skeletal muscle. The largest response is in skeletal muscle, where the cyclic nucleotide concentration is elevated more than 500-fold. Glia and muscle cells, but not nerve cells, respond to dopamine with increased cyclic AMP accumulation. This response appears to be mediated through a beta-adrenoreceptor.", "contents": "Neurotransmitter regulation of adenosine 3',5'-monophosphate in clonal nerve, glia, and muscle cell lines. Norepinephrine increases the intracellular level of adenosine 3',5'-monophosphate (cyclic AMP) in clonal cell lines of nerve, glia, smooth muscel, and skeletal muscle. The largest response is in skeletal muscle, where the cyclic nucleotide concentration is elevated more than 500-fold. Glia and muscle cells, but not nerve cells, respond to dopamine with increased cyclic AMP accumulation. This response appears to be mediated through a beta-adrenoreceptor."} {"id": "PMID:176729", "title": "[A propos of 210 emergency endoscopies in upper digestive hemorrhage].", "content": "The authors report their experience of 210 fiber endoscopies carried out as an emergency for upper digestive hemorrhage. They emphasize the necessity of early examination and only consider here examinations carried out within 12 hours from the start of the hemorrhage. In 91.4 % of cases, a correct diagnosis was possible. More than 20% of the patients had at least two lesions liable to cause hemorrhage. In cirrhosis, esophageal varices were the cause of hemorrhage in only 50% of cases.", "contents": "[A propos of 210 emergency endoscopies in upper digestive hemorrhage]. The authors report their experience of 210 fiber endoscopies carried out as an emergency for upper digestive hemorrhage. They emphasize the necessity of early examination and only consider here examinations carried out within 12 hours from the start of the hemorrhage. In 91.4 % of cases, a correct diagnosis was possible. More than 20% of the patients had at least two lesions liable to cause hemorrhage. In cirrhosis, esophageal varices were the cause of hemorrhage in only 50% of cases."} {"id": "PMID:176730", "title": "[Endoscopic resection of colonic polyps. A propos of 45 polypectomies].", "content": "Endoscopic resection of polyps of the colon is, no doubt, a considerable therapeutic advance. It avoids surgical operation permits histological examination and makes simple biopsy unnecessary. It is indicated in the presence of pediculated polyps of a diameter or less than 3 cm, whatever the site of the polyp. Thus we were able to remove 45 polyps without complications. The method is not indicated in a large size polyp, sessile polyps or diffuse polyposis. The follow-up is still insufficient to assess : 1) the true risk of resection which can only be undertaken after long experience of colonoscopy ; 2) the frequency or recurrent adenomas. Endoscopic resection is at present the simplest method of detection and treatment of carcinoma in situ of the colon of which we observed four cases in our series. The problem of surgical reoperation is discussed.", "contents": "[Endoscopic resection of colonic polyps. A propos of 45 polypectomies]. Endoscopic resection of polyps of the colon is, no doubt, a considerable therapeutic advance. It avoids surgical operation permits histological examination and makes simple biopsy unnecessary. It is indicated in the presence of pediculated polyps of a diameter or less than 3 cm, whatever the site of the polyp. Thus we were able to remove 45 polyps without complications. The method is not indicated in a large size polyp, sessile polyps or diffuse polyposis. The follow-up is still insufficient to assess : 1) the true risk of resection which can only be undertaken after long experience of colonoscopy ; 2) the frequency or recurrent adenomas. Endoscopic resection is at present the simplest method of detection and treatment of carcinoma in situ of the colon of which we observed four cases in our series. The problem of surgical reoperation is discussed."} {"id": "PMID:176731", "title": "[Routine gastric fiber endoscopy in severe head injuries].", "content": "Gastric lesions in severe cranial trauma are almost constant, whether the patients have bled or not. Routine fiber endoscopy in 63 cases permited the authors to discover various types of lesion, some in association, whether diffuse or localised, e.g. oedema or congestion, viz. congestion, purpura, various sized ulcers, usually situated high up in the stomach, sometimes in the antrum ; their course, whether rapid or not, was often intermittent. Endoscopy is the best method of diagnosis permitting appropriate treatment.", "contents": "[Routine gastric fiber endoscopy in severe head injuries]. Gastric lesions in severe cranial trauma are almost constant, whether the patients have bled or not. Routine fiber endoscopy in 63 cases permited the authors to discover various types of lesion, some in association, whether diffuse or localised, e.g. oedema or congestion, viz. congestion, purpura, various sized ulcers, usually situated high up in the stomach, sometimes in the antrum ; their course, whether rapid or not, was often intermittent. Endoscopy is the best method of diagnosis permitting appropriate treatment."} {"id": "PMID:176732", "title": "Discontinued thrombolytic treatment: initial biological results.", "content": "Changes in blood coagulation following the action of intermittent treatment with streptokinase are studied : 1) Fibrinogenemia remains at a concentration slightly higher than that obtained after the first 16 hour perfusion. 2) The thrombin time becomes considerably longer on the first day, then becomes shorter and remains slightly long throughout treatment. The theoretical interest of the rise in plasminogen levels during interruption of perfusions of streptokinase is discussed.", "contents": "Discontinued thrombolytic treatment: initial biological results. Changes in blood coagulation following the action of intermittent treatment with streptokinase are studied : 1) Fibrinogenemia remains at a concentration slightly higher than that obtained after the first 16 hour perfusion. 2) The thrombin time becomes considerably longer on the first day, then becomes shorter and remains slightly long throughout treatment. The theoretical interest of the rise in plasminogen levels during interruption of perfusions of streptokinase is discussed."} {"id": "PMID:176733", "title": "[Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].", "content": "38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment.", "contents": "[Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases]. 38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment."} {"id": "PMID:176734", "title": "Rare tumors of the ear, nose and throat: synovial sarcoma of the head and neck.", "content": "Synovial sarcoma is a rare neoplasm of mesenchymal origin. Contrary to earlier beliefs, this tumor does not arise from the synovial lining of joints and bursae, but develops from pluripotential mesenchymal cells through abnormal differentiation into synovial neoplasms. Macroscopically there are no distinguishing features. Microscopically the tumor is characterized by a biphasic pattern of pseudoepithelial cells and a spindle cell element with fibrosarcomatous appearance. To establish a diagnosis both features must be present, yet their relative proportions vary markedly. The tumor occurs most frequently in the extremities and rarely in other areas. Only 19 cases of synovial sarcoma of the head and neck have been reported in the literature. Two additional cases, one of the hypopharynx and one of the cheek, are reported herein.", "contents": "Rare tumors of the ear, nose and throat: synovial sarcoma of the head and neck. Synovial sarcoma is a rare neoplasm of mesenchymal origin. Contrary to earlier beliefs, this tumor does not arise from the synovial lining of joints and bursae, but develops from pluripotential mesenchymal cells through abnormal differentiation into synovial neoplasms. Macroscopically there are no distinguishing features. Microscopically the tumor is characterized by a biphasic pattern of pseudoepithelial cells and a spindle cell element with fibrosarcomatous appearance. To establish a diagnosis both features must be present, yet their relative proportions vary markedly. The tumor occurs most frequently in the extremities and rarely in other areas. Only 19 cases of synovial sarcoma of the head and neck have been reported in the literature. Two additional cases, one of the hypopharynx and one of the cheek, are reported herein."} {"id": "PMID:176735", "title": "Early bilateral eighth nerve involvement in meningococcal meningitis.", "content": "A male Navy recruit had hearing loss and bilateral otitis media. Meningeal signs, not initially present, developed approximately 48 hours after admission to the hospital. Type Y meningococcus was isolated from blood cultures drawn after two days of ampicillin administered orally. Permanent, bilateral, vestibular and auditory loss resulted, in spite of adequate doses of penicillin. This unusual presentation of bilateral eighth nerve involvement was thought to be due to a localized, bilateral meningococcal labyrinthitis.", "contents": "Early bilateral eighth nerve involvement in meningococcal meningitis. A male Navy recruit had hearing loss and bilateral otitis media. Meningeal signs, not initially present, developed approximately 48 hours after admission to the hospital. Type Y meningococcus was isolated from blood cultures drawn after two days of ampicillin administered orally. Permanent, bilateral, vestibular and auditory loss resulted, in spite of adequate doses of penicillin. This unusual presentation of bilateral eighth nerve involvement was thought to be due to a localized, bilateral meningococcal labyrinthitis."} {"id": "PMID:176736", "title": "The effect of dengue virus infection on the clinical sequelae of Japanese encephalitis: a one year follow-up study in Thailand.", "content": "In order to determine if prior dengue virus infection reduces the severity of Japanese encephalitis (JE), we examined 127 patients hospitalized during the 1970 JE epidemic in the Chiangmai and Lampang Valleys of northern Thailand. Patients were studied during the first 30 days after onset of JE; 120 of these patients were examined one year later for residual neurologic sequelae. About 21% of patients had serological evidence of a prior dengue virus infection. Morbidity and mortality in patients with and without prior dengue virus experience were compared. These comparisons were made within two age groups to exclude differences due to age alone;", "contents": "The effect of dengue virus infection on the clinical sequelae of Japanese encephalitis: a one year follow-up study in Thailand. In order to determine if prior dengue virus infection reduces the severity of Japanese encephalitis (JE), we examined 127 patients hospitalized during the 1970 JE epidemic in the Chiangmai and Lampang Valleys of northern Thailand. Patients were studied during the first 30 days after onset of JE; 120 of these patients were examined one year later for residual neurologic sequelae. About 21% of patients had serological evidence of a prior dengue virus infection. Morbidity and mortality in patients with and without prior dengue virus experience were compared. These comparisons were made within two age groups to exclude differences due to age alone;"} {"id": "PMID:176737", "title": "Parasitology survey in the Palu Valley, central Sulawesi (Celebes), Indonesia.", "content": "A survey was undertaken in the Palu Valley, Central Sulasesi to determine whether schisto somiasis japonica was endemic in the area and to determine the prevalences rates of intestinal and blood parasites. Seven villages along the Palu River drainage system with an estimated popualtion of 18,700 were surveyed and 2,433 stools, 3,651 blood smears and 1,167 sera were collected and examined.", "contents": "Parasitology survey in the Palu Valley, central Sulawesi (Celebes), Indonesia. A survey was undertaken in the Palu Valley, Central Sulasesi to determine whether schisto somiasis japonica was endemic in the area and to determine the prevalences rates of intestinal and blood parasites. Seven villages along the Palu River drainage system with an estimated popualtion of 18,700 were surveyed and 2,433 stools, 3,651 blood smears and 1,167 sera were collected and examined."} {"id": "PMID:176738", "title": "Portacaval shunt in two patients with homozygous type II hyperlipoproteinaemia.", "content": "We report the clinical and biochemical course of 2 patients who underwent portacaval shunting for the relief of homozygous type II hyperlipoproteinaemia. In our first patient, the initial favourable clinical and biochemical response subsequently deteriorated and a splenoportogram revealed the presence of a blocked splenic vein with a large collateral blood supply to the liver. The second patient has responded quite dramatically; there has been relief of her preoperative anginal attacks and a significant fall in her plasma cholesterol concentration. The present role of portacaval shunts in the management of this conditions is discussed.", "contents": "Portacaval shunt in two patients with homozygous type II hyperlipoproteinaemia. We report the clinical and biochemical course of 2 patients who underwent portacaval shunting for the relief of homozygous type II hyperlipoproteinaemia. In our first patient, the initial favourable clinical and biochemical response subsequently deteriorated and a splenoportogram revealed the presence of a blocked splenic vein with a large collateral blood supply to the liver. The second patient has responded quite dramatically; there has been relief of her preoperative anginal attacks and a significant fall in her plasma cholesterol concentration. The present role of portacaval shunts in the management of this conditions is discussed."} {"id": "PMID:176739", "title": "Pituitary and ovarian function in women with vesicovaginal fistuale after obstructed and prolonged labour.", "content": "This study concerns 11 patients with menstrual disorders dating back to an obstructed and prolonged labour, and 5 women with similar histories but without menstrual disorders. All patients were able to secrete gonadotrophins. According to the gonadotrophin pattern, the patients could be divided into three groups: in the amenorrhoeic and in 2 normally menstruating women various degrees of suppression of basal and peak levels of luteinising hormone (LH) could be observed; patients with infrequent menstrual periods showed temporarily arrested secretion of gonadotrophins and ovarian steroids; and in polymerrhoea a non-cyclic but high secretion was seen. The gonadotrophin response to oestrogen levels was temporarily or permanently disordered in all but 3 patients in this series, whereas an ovarian refractoriness to gonadotrophins was only infrequently observed. There were 2 cases of 'ovulatory amenorrhoea' as judged by the normal profiles of ovarian steroids. Biopsies indicated inadequate endometrial transformation in many cases of amenorrhoea. Abnormal responses to the stimulatory tests of pituitary secretion of human growth hormone (HGH) and/or LH were seen in 6 patients. The study suggests that menstrual disorders after obstructed labour are associated with derangement of different hypophyseotrophic areas of the hypothalamus.", "contents": "Pituitary and ovarian function in women with vesicovaginal fistuale after obstructed and prolonged labour. This study concerns 11 patients with menstrual disorders dating back to an obstructed and prolonged labour, and 5 women with similar histories but without menstrual disorders. All patients were able to secrete gonadotrophins. According to the gonadotrophin pattern, the patients could be divided into three groups: in the amenorrhoeic and in 2 normally menstruating women various degrees of suppression of basal and peak levels of luteinising hormone (LH) could be observed; patients with infrequent menstrual periods showed temporarily arrested secretion of gonadotrophins and ovarian steroids; and in polymerrhoea a non-cyclic but high secretion was seen. The gonadotrophin response to oestrogen levels was temporarily or permanently disordered in all but 3 patients in this series, whereas an ovarian refractoriness to gonadotrophins was only infrequently observed. There were 2 cases of 'ovulatory amenorrhoea' as judged by the normal profiles of ovarian steroids. Biopsies indicated inadequate endometrial transformation in many cases of amenorrhoea. Abnormal responses to the stimulatory tests of pituitary secretion of human growth hormone (HGH) and/or LH were seen in 6 patients. The study suggests that menstrual disorders after obstructed labour are associated with derangement of different hypophyseotrophic areas of the hypothalamus."} {"id": "PMID:176740", "title": "Antibacterial activity of oxidized regenerated cellulose.", "content": "It has been demonstrated that oxidized regenerated cellulose promptly and markedly reduces the bacterial census of ten different strains of common pathogens when exposed to them in vitro. This was not true of two other hemostatic agents tested, namely, absorbable gelatin sponge and topical thrombin. Wounds in guinea pigs in which oxidized regenerated cellulose was placed and infected with one of three pathogens had healing per primum in 39 of 40 instances. In similar control wounds and incisions in which absorbable gelatin sponge was placed, sepsis of the wound developed in 19 of 20 of the control group and in 39 of 40 guinea pigs in the absorbable gelatin sponge group.", "contents": "Antibacterial activity of oxidized regenerated cellulose. It has been demonstrated that oxidized regenerated cellulose promptly and markedly reduces the bacterial census of ten different strains of common pathogens when exposed to them in vitro. This was not true of two other hemostatic agents tested, namely, absorbable gelatin sponge and topical thrombin. Wounds in guinea pigs in which oxidized regenerated cellulose was placed and infected with one of three pathogens had healing per primum in 39 of 40 instances. In similar control wounds and incisions in which absorbable gelatin sponge was placed, sepsis of the wound developed in 19 of 20 of the control group and in 39 of 40 guinea pigs in the absorbable gelatin sponge group."} {"id": "PMID:176741", "title": "Orthotopic liver transplantation in ninety-three patients.", "content": "During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures.", "contents": "Orthotopic liver transplantation in ninety-three patients. During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures."} {"id": "PMID:176742", "title": "Polyglactin 910 suture absorption and the role of cellular enzymes.", "content": "Enzyme histochemical procedures for both hydrolase and oxidoreductase enzyme activity were applied to cryostat sections of polyglactin 910 suture implant sites. Sutures were implanted either solely in tissue or in a combination of in vitro incubation followed by implantation in vivo for total time periods of seven to 56 days. Suture absorption rates were also measured. It is concluded from the results that neither cellular nor enzyme activity is necessary for the degradation and absorption of polyglactin 910 sutures. This conclusion is based on similar absorption rates for sutures implanted solely in vivo and sutures treated in vitro and then implanted in tissue to give equivalent time spans. There were strong indications, however, that the products of suture hydrolysis are probably metabolized through the oxidative enzyme systems of cells adjacent to the suture. This mechanism of polyglactin 910 suture absorption is quite different from that observed and reported for catgut absorbable sutures.", "contents": "Polyglactin 910 suture absorption and the role of cellular enzymes. Enzyme histochemical procedures for both hydrolase and oxidoreductase enzyme activity were applied to cryostat sections of polyglactin 910 suture implant sites. Sutures were implanted either solely in tissue or in a combination of in vitro incubation followed by implantation in vivo for total time periods of seven to 56 days. Suture absorption rates were also measured. It is concluded from the results that neither cellular nor enzyme activity is necessary for the degradation and absorption of polyglactin 910 sutures. This conclusion is based on similar absorption rates for sutures implanted solely in vivo and sutures treated in vitro and then implanted in tissue to give equivalent time spans. There were strong indications, however, that the products of suture hydrolysis are probably metabolized through the oxidative enzyme systems of cells adjacent to the suture. This mechanism of polyglactin 910 suture absorption is quite different from that observed and reported for catgut absorbable sutures."} {"id": "PMID:176744", "title": "Ascorbate inhibition of 6-aminonicotinamide teratogenesis in chicken embryos.", "content": "Chicken eggs of 4 or 6 days of incubation were injected with 10 mug 6-aminonicotinamide (6-AN) or 6-AN plus various doses of sodium ascorbate, calcium ascorbate, or ascorbic acid; 11-day embryos were examined grossly and histologically. 6-AN-treated embryos had various degrees of micromelia and were reduced in overall size. All three ascorbates inhibited 6-AN teratogenesis but not completely. The extent of inhibition was dose related. Increased amounts of intercellular matrix and decreased necrosis of chondrocytes in the limb cartilage of protected embryos correlated with the gross findings.", "contents": "Ascorbate inhibition of 6-aminonicotinamide teratogenesis in chicken embryos. Chicken eggs of 4 or 6 days of incubation were injected with 10 mug 6-aminonicotinamide (6-AN) or 6-AN plus various doses of sodium ascorbate, calcium ascorbate, or ascorbic acid; 11-day embryos were examined grossly and histologically. 6-AN-treated embryos had various degrees of micromelia and were reduced in overall size. All three ascorbates inhibited 6-AN teratogenesis but not completely. The extent of inhibition was dose related. Increased amounts of intercellular matrix and decreased necrosis of chondrocytes in the limb cartilage of protected embryos correlated with the gross findings."} {"id": "PMID:176745", "title": "NAD precursors as antiteratogens against aminothiadiazole.", "content": "The teratogen 2-amino-1,3,4-thiadiazole (ATDA) is an antagonist of nicotinamide, and may act by interfering with the synthesis or utilization of the coenzyme nicotinamide adenine dinucleotide (NAD). Several compounds that can be converted to NAD were tested as antiteratogens against ATDA. At day 11 of gestation (sperm day = day 0) pregnant Wistar-derived rats were given single ip injections of ATDA (100 mg/kg), or ATDA immediately followed by the suspected antiteratogen ip or by gavage, or the antiteratogen alone. Compounds tested were NAD, nicotinamide, nicotinic acid, quinolinic acid, kynurenine sulfate, and L-tryptophan, in doses of 10-200 mg per animal. At autopsy (day 20) fetuses were recovered and examined. It was found that each antiteratogen significantly reduced the frequency of ATDA-induced resorptions and malformations. At certain doses each anteteratogen gave complete protection against ATDA-induced malformations in some, but not all, litters. These results support the hypothesis that ADTA interferes with the synthesis or utilization of NAD and suggest that substances converted to NAD act as antiteratogens against ATDA.", "contents": "NAD precursors as antiteratogens against aminothiadiazole. The teratogen 2-amino-1,3,4-thiadiazole (ATDA) is an antagonist of nicotinamide, and may act by interfering with the synthesis or utilization of the coenzyme nicotinamide adenine dinucleotide (NAD). Several compounds that can be converted to NAD were tested as antiteratogens against ATDA. At day 11 of gestation (sperm day = day 0) pregnant Wistar-derived rats were given single ip injections of ATDA (100 mg/kg), or ATDA immediately followed by the suspected antiteratogen ip or by gavage, or the antiteratogen alone. Compounds tested were NAD, nicotinamide, nicotinic acid, quinolinic acid, kynurenine sulfate, and L-tryptophan, in doses of 10-200 mg per animal. At autopsy (day 20) fetuses were recovered and examined. It was found that each antiteratogen significantly reduced the frequency of ATDA-induced resorptions and malformations. At certain doses each anteteratogen gave complete protection against ATDA-induced malformations in some, but not all, litters. These results support the hypothesis that ADTA interferes with the synthesis or utilization of NAD and suggest that substances converted to NAD act as antiteratogens against ATDA."} {"id": "PMID:176747", "title": "Bronchorrhoea.", "content": "Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases. The rheological and chemical characteristics of the sputum are here described. Levels of viscosity, dry weight, N-acetyl neuraminic acid (NANA), fucose, and sulphate fall between those in saliva and mucoid sputum from chronic lung diseases. These levels were always higher in bronchorrhoea sputum than in saliva and therefore may be used in the differential diagnosis of bronchorrhoea and hypersalivation. Bronchorrhoea sputum has the constituents of a bronchial secretion but is low in acid glycoprotein. Certain other features are commonly found - a large amount of froth, increase in viscosity with time, and separation into two phases. Some cases respond to steroids, particularly when the levels of NANA in the sputum are low.", "contents": "Bronchorrhoea. Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases. The rheological and chemical characteristics of the sputum are here described. Levels of viscosity, dry weight, N-acetyl neuraminic acid (NANA), fucose, and sulphate fall between those in saliva and mucoid sputum from chronic lung diseases. These levels were always higher in bronchorrhoea sputum than in saliva and therefore may be used in the differential diagnosis of bronchorrhoea and hypersalivation. Bronchorrhoea sputum has the constituents of a bronchial secretion but is low in acid glycoprotein. Certain other features are commonly found - a large amount of froth, increase in viscosity with time, and separation into two phases. Some cases respond to steroids, particularly when the levels of NANA in the sputum are low."} {"id": "PMID:176753", "title": "Effect of chilling on platelet cyclic adenosine 3:5-monophosphate and adenylate cyclase activity.", "content": "Exposure of platelets to 1 C led to a transient increase in cyclic AMP levels (determined either by a protein binding method or by radioimmunoassay) within five to ten minutes reaching a maximum 10 to 15 minutes after chilling was begun and returning subsequently to baseline values. Addition of EDTA to the platelet suspension medium prevented this increase. Rewarming at 37 C produced a sudden reduction in platelet cyclic AMP. To determine whether the cold-induced increase in cyclic AMP was due to a transient stimulation of platelet adenylate cyclase or a rapid inhibition of phosphodiesterase, these enzymes were assayed in ruptured platelet suspensions. Platelet adenylate cyclase activity was found to possess certain characteristics similar to those of the enzyme derived from other sources but there was a marked potentiation of fluoride-stimulated adenylate cyclase activity by 0.001 M EDTA. This effect was limited to low EDTA concentrations. Exposure of platelets to 1 C for up to 60 minutes did not increase adenylate cyclase activity but lowered it substantially compared with controls kept at room temperature. Phosphodiesterase activity at 1 C was depressed sooner and to a greater extent than was adenylate cyclase. The transient rise in cyclic AMP levels in chilled platelets appears to be due to a disproportionate reduction of cyclic nucleotide phosphodiesterase activity.", "contents": "Effect of chilling on platelet cyclic adenosine 3:5-monophosphate and adenylate cyclase activity. Exposure of platelets to 1 C led to a transient increase in cyclic AMP levels (determined either by a protein binding method or by radioimmunoassay) within five to ten minutes reaching a maximum 10 to 15 minutes after chilling was begun and returning subsequently to baseline values. Addition of EDTA to the platelet suspension medium prevented this increase. Rewarming at 37 C produced a sudden reduction in platelet cyclic AMP. To determine whether the cold-induced increase in cyclic AMP was due to a transient stimulation of platelet adenylate cyclase or a rapid inhibition of phosphodiesterase, these enzymes were assayed in ruptured platelet suspensions. Platelet adenylate cyclase activity was found to possess certain characteristics similar to those of the enzyme derived from other sources but there was a marked potentiation of fluoride-stimulated adenylate cyclase activity by 0.001 M EDTA. This effect was limited to low EDTA concentrations. Exposure of platelets to 1 C for up to 60 minutes did not increase adenylate cyclase activity but lowered it substantially compared with controls kept at room temperature. Phosphodiesterase activity at 1 C was depressed sooner and to a greater extent than was adenylate cyclase. The transient rise in cyclic AMP levels in chilled platelets appears to be due to a disproportionate reduction of cyclic nucleotide phosphodiesterase activity."} {"id": "PMID:176754", "title": "[Importance of concentration factors in cryoinjury of lysosomes].", "content": "The injury degree of lysosomes isolated from the rat liver under low temperature conditions was studied with respect to nonsedimented hydrolases activities (acid RNases, DNase, phosphatase, cathepsins) taken as a biochemical criterium of lysosomal membrane stability. The lysosomal fraction was resuspended in 0.15 M NaCl solution and frozen in the liquid N2 vapours up to --30 degrees C. According to the thermographic analysis data the samples were thawed and studied at different stages of cooling. The activity of the studied hydrolases was established to increase most considerably during the water crystallization period and at the NaCl eutectic point. Hydrolytic enzymes release from lysosomes proved to be dependent on the thawing rate and NaCl concentration. The obtained data indicate to the importance of concentration factors in lysosomal membrane cryoinjury.", "contents": "[Importance of concentration factors in cryoinjury of lysosomes]. The injury degree of lysosomes isolated from the rat liver under low temperature conditions was studied with respect to nonsedimented hydrolases activities (acid RNases, DNase, phosphatase, cathepsins) taken as a biochemical criterium of lysosomal membrane stability. The lysosomal fraction was resuspended in 0.15 M NaCl solution and frozen in the liquid N2 vapours up to --30 degrees C. According to the thermographic analysis data the samples were thawed and studied at different stages of cooling. The activity of the studied hydrolases was established to increase most considerably during the water crystallization period and at the NaCl eutectic point. Hydrolytic enzymes release from lysosomes proved to be dependent on the thawing rate and NaCl concentration. The obtained data indicate to the importance of concentration factors in lysosomal membrane cryoinjury."} {"id": "PMID:176759", "title": "[The effect of standardised sodium hypochlorite solution on bacteria pathogenic for the urinary tract (author's transl)].", "content": "Stable sodium hypochlorite solution shows excellent disinfectant properties, even in higher dilution. Parallel to clinical tests in vitro experiments were made to show the changes of morphology of bacteria pathogenic for the urinary tract by scanning microscope. Two hours after incubation of the bacteria with sodium hypochlorite solution containing 40 mg available chlorine/1 severe damages of the bacterial morphology up to complete destruction were evident in all cases. Gram-negative rod-shaped bacilli were more, gram-positive cocci were less damaged.", "contents": "[The effect of standardised sodium hypochlorite solution on bacteria pathogenic for the urinary tract (author's transl)]. Stable sodium hypochlorite solution shows excellent disinfectant properties, even in higher dilution. Parallel to clinical tests in vitro experiments were made to show the changes of morphology of bacteria pathogenic for the urinary tract by scanning microscope. Two hours after incubation of the bacteria with sodium hypochlorite solution containing 40 mg available chlorine/1 severe damages of the bacterial morphology up to complete destruction were evident in all cases. Gram-negative rod-shaped bacilli were more, gram-positive cocci were less damaged."} {"id": "PMID:176755", "title": "[Activity of carbohydrate-metabolizing enzymes and content of carbohydrate and nitrogen compounds in muscles of young cattle depending on breed and sex].", "content": "The activity of glycolysis and glyconeogenesis enzymes, content of carbohydrate and nitrogen compounds were studied in muscles of 15-month cattle of different sex of the black-piebald breed and its crosses with bulls of two meat breeds Hereford and Limousine. In the muscles of bulls the activity of phosphoglucomutase, phosphohexoisomerase, aldolase and fructose-1,6-diphosphatase is considerably higher (except of the activity of phosphoglucomutase and phosphohexoisomerase in the muscles of pure-bred black-piebald animals for which difference is not statistically reliable) and the content of glycogen, glucose, fructose, lactic acid, free and phosphorylated pentoses of nonadenylic compounds is essentially lower than in the muscle tissue of heifers of analogous breed groups. A higher activity of carbohydrate metabolism enzymes (especially aldolase and fructose-1,6-diphosphate) and a higher content of total pentoses, the adenylic system pentoses, ATP phosphorus in the muscles of the cross Limousine and Hereford bulls and Limousine heifers as compared to the pure-bred black-piebald animals of the corresponding sex coincide with a greater increase in the muscular tissue and more intensive synthesis of proteins in it. A considerably lower level of glycogen, glucose, fructose and a relatively high activity of carbohydrate metabolism enzymes in the muscles of cross young cattle show that disintegration of these carbohydrates is in excess of their synthesis, that is due to an increase in the energy demand connected with a more intensive synthesis of proteins in the muscular tissue. Therefore, in the authors opinion the performed kill of the cross Limousine and Hereford bulls as well as Limousine heifers, is somewhat untimely and unreasonable. At the same time the activity of all the studied enzymes in the muscles of the cross Hereford heifers, vice versa, is considerably lower as compared to the black-piebald heifers and coincides with a low gain in live weight and muscular tissue, a more rapid accumulation of glycogen and lipids and a more delayed--of proteins in the muscular tissue, that evidences for their early maturity. Therefore the further raising of the cross Hereford heifers in the farm for obtaining meat is economically less profitable. The data obtained give grounds to recommend determination of the activity of carbohydrate metabolism enzymes, especially of aldolase and fructose-1,6-diphosphate, as a test for checking the muscular tissue growth and for prognosing the meat productivity in the growing pure-bred and cross young cattle of different sex.", "contents": "[Activity of carbohydrate-metabolizing enzymes and content of carbohydrate and nitrogen compounds in muscles of young cattle depending on breed and sex]. The activity of glycolysis and glyconeogenesis enzymes, content of carbohydrate and nitrogen compounds were studied in muscles of 15-month cattle of different sex of the black-piebald breed and its crosses with bulls of two meat breeds Hereford and Limousine. In the muscles of bulls the activity of phosphoglucomutase, phosphohexoisomerase, aldolase and fructose-1,6-diphosphatase is considerably higher (except of the activity of phosphoglucomutase and phosphohexoisomerase in the muscles of pure-bred black-piebald animals for which difference is not statistically reliable) and the content of glycogen, glucose, fructose, lactic acid, free and phosphorylated pentoses of nonadenylic compounds is essentially lower than in the muscle tissue of heifers of analogous breed groups. A higher activity of carbohydrate metabolism enzymes (especially aldolase and fructose-1,6-diphosphate) and a higher content of total pentoses, the adenylic system pentoses, ATP phosphorus in the muscles of the cross Limousine and Hereford bulls and Limousine heifers as compared to the pure-bred black-piebald animals of the corresponding sex coincide with a greater increase in the muscular tissue and more intensive synthesis of proteins in it. A considerably lower level of glycogen, glucose, fructose and a relatively high activity of carbohydrate metabolism enzymes in the muscles of cross young cattle show that disintegration of these carbohydrates is in excess of their synthesis, that is due to an increase in the energy demand connected with a more intensive synthesis of proteins in the muscular tissue. Therefore, in the authors opinion the performed kill of the cross Limousine and Hereford bulls as well as Limousine heifers, is somewhat untimely and unreasonable. At the same time the activity of all the studied enzymes in the muscles of the cross Hereford heifers, vice versa, is considerably lower as compared to the black-piebald heifers and coincides with a low gain in live weight and muscular tissue, a more rapid accumulation of glycogen and lipids and a more delayed--of proteins in the muscular tissue, that evidences for their early maturity. Therefore the further raising of the cross Hereford heifers in the farm for obtaining meat is economically less profitable. The data obtained give grounds to recommend determination of the activity of carbohydrate metabolism enzymes, especially of aldolase and fructose-1,6-diphosphate, as a test for checking the muscular tissue growth and for prognosing the meat productivity in the growing pure-bred and cross young cattle of different sex."} {"id": "PMID:176760", "title": "[Clinical use of sodium hypochlorite for local treatment and prevention of urinary tract infections and therapy of contracted bladders (author's transl)].", "content": "A stable commercial electrolytic sodium hypochlorite solution was tested in 63 urologic patients. The complete germicidal action against all sorts of bacteria was shown in suspension-tests. Irrigation studies of the infected bladder were performed. It was found that continued bladder irrigations were necessary to stop bacterial ascension from the infected urethra. Bladder capacity was increased in 6 of 8 patients with nonmalignant contracted bladder or interstitial cystitis. Desinfection with sodium hypochlorite in urologic practice is cheap, easy to perform and diminishes the risk of hospitalism. Clinical studies confirmed the absence of general or local toxicity.", "contents": "[Clinical use of sodium hypochlorite for local treatment and prevention of urinary tract infections and therapy of contracted bladders (author's transl)]. A stable commercial electrolytic sodium hypochlorite solution was tested in 63 urologic patients. The complete germicidal action against all sorts of bacteria was shown in suspension-tests. Irrigation studies of the infected bladder were performed. It was found that continued bladder irrigations were necessary to stop bacterial ascension from the infected urethra. Bladder capacity was increased in 6 of 8 patients with nonmalignant contracted bladder or interstitial cystitis. Desinfection with sodium hypochlorite in urologic practice is cheap, easy to perform and diminishes the risk of hospitalism. Clinical studies confirmed the absence of general or local toxicity."} {"id": "PMID:176756", "title": "[Peculiarities of disturbances in oxidation and phosphorylation processes in rat liver under the effect of mononitrophenols].", "content": "It is determined that ortho- and n-nitrophenol introduced into the stomach (0.80 and 0.11 g/kg, respectively) inhibit the activity of cytochrome oxydase (by 21% at an average), cause an increase in the content of NADH (by 35 and 27%) and a decrease in ATP (by 38 and 36%, respectively), split the oxidation and phosphorylation processes in the rat liver tissue. The content of NAD+, AMP and ADP, lactate, the activity of K+, Na+-ATPase and lactate dehydrogenase do not change.", "contents": "[Peculiarities of disturbances in oxidation and phosphorylation processes in rat liver under the effect of mononitrophenols]. It is determined that ortho- and n-nitrophenol introduced into the stomach (0.80 and 0.11 g/kg, respectively) inhibit the activity of cytochrome oxydase (by 21% at an average), cause an increase in the content of NADH (by 35 and 27%) and a decrease in ATP (by 38 and 36%, respectively), split the oxidation and phosphorylation processes in the rat liver tissue. The content of NAD+, AMP and ADP, lactate, the activity of K+, Na+-ATPase and lactate dehydrogenase do not change."} {"id": "PMID:176757", "title": "[Interrelation between changes in RNA transcription and glycine-14C incorporation into protein peculiar to hepatoma PC-1].", "content": "Incorporation of labelled precursor, glycin-1-14C, into the fraction and individual subfractions of blood serum immunoglobulin G (namely into protein positively reacting in the precipitation test) testifies to the fact that at early stages of the tumour development in the rat organism there occurs an intensive synthesis of protein peculiar to hepatoma PC-1. Actinomycin D in a dose blocking the appearance of the peculiar protein in the blood serum of rats with the tumour has a selective effect on the transcription of liver nuclear RNA in rats with hepatoma PC-1. Its inhibitory effect is most pronounced with respect to ribosomal RNA and one of the fractions of DNA-like RNA--RNA-85. It is observed that the fraction of DNA-like RNA--RNA-63, being stable to the effect of actinomycin D at normal state and with liver regeneration is inhibited to some extent by the antibiotic with the presence of the tumour in the rat organism.", "contents": "[Interrelation between changes in RNA transcription and glycine-14C incorporation into protein peculiar to hepatoma PC-1]. Incorporation of labelled precursor, glycin-1-14C, into the fraction and individual subfractions of blood serum immunoglobulin G (namely into protein positively reacting in the precipitation test) testifies to the fact that at early stages of the tumour development in the rat organism there occurs an intensive synthesis of protein peculiar to hepatoma PC-1. Actinomycin D in a dose blocking the appearance of the peculiar protein in the blood serum of rats with the tumour has a selective effect on the transcription of liver nuclear RNA in rats with hepatoma PC-1. Its inhibitory effect is most pronounced with respect to ribosomal RNA and one of the fractions of DNA-like RNA--RNA-85. It is observed that the fraction of DNA-like RNA--RNA-63, being stable to the effect of actinomycin D at normal state and with liver regeneration is inhibited to some extent by the antibiotic with the presence of the tumour in the rat organism."} {"id": "PMID:176764", "title": "An outbreak of acute pneumonia in young, single-suckled calves.", "content": "An outbreak of acute severe pneumonia which affected six to 14-week-old single-suckled calves, resulted in 45/77 requiring treatment. The examination of paired sera from all affected calves revealed that neither an adenovirus, non infectious bovine rhinotracheitis virus nor parainfluenza 3 virus was involved. The acute exudative interstitial pneumonia found at post mortem was typical of pneumonic pasteurellosis.", "contents": "An outbreak of acute pneumonia in young, single-suckled calves. An outbreak of acute severe pneumonia which affected six to 14-week-old single-suckled calves, resulted in 45/77 requiring treatment. The examination of paired sera from all affected calves revealed that neither an adenovirus, non infectious bovine rhinotracheitis virus nor parainfluenza 3 virus was involved. The acute exudative interstitial pneumonia found at post mortem was typical of pneumonic pasteurellosis."} {"id": "PMID:176765", "title": "Relationship of porcine cytomegalovirus and B bronchiseptica to atrophic rhinitis in gnotobiotic piglets.", "content": "Both porcine cytomegalovirus (PCMV) and Bordetella bronchiseptica produced rhinitis and pneumonia when inoculated intranasally into young gnotobiotic pigs. With PCMV the nasal lesions were confirmed to the lamina propria, while Bordetella produced atrophy of the turbinate bones and hyperplasia and degeneration of the nasal epithelium. Some exacerbation of the lesions was observed in the nasal mucosa of pigs given both agents, but the degree of bone atrophy was not increased.", "contents": "Relationship of porcine cytomegalovirus and B bronchiseptica to atrophic rhinitis in gnotobiotic piglets. Both porcine cytomegalovirus (PCMV) and Bordetella bronchiseptica produced rhinitis and pneumonia when inoculated intranasally into young gnotobiotic pigs. With PCMV the nasal lesions were confirmed to the lamina propria, while Bordetella produced atrophy of the turbinate bones and hyperplasia and degeneration of the nasal epithelium. Some exacerbation of the lesions was observed in the nasal mucosa of pigs given both agents, but the degree of bone atrophy was not increased."} {"id": "PMID:176766", "title": "Initial studies on \"six months disease\" in sheep.", "content": "Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name \"Six months disease\" and enterotoxaemia are considered to be identical diseases.", "contents": "Initial studies on \"six months disease\" in sheep. Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name \"Six months disease\" and enterotoxaemia are considered to be identical diseases."} {"id": "PMID:176770", "title": "[Studies of the complement fixation reaction in infectious rhinotracheitis in cattle].", "content": "The complement-fixation reaction was used in the diagnosis of infectious bovine rhinotracheitis establishing its specificity and effectiveness. Highest titers of the antigens tested (up to 1:16) showed antigens that were concentrated with the use of poly ethylene glycol. In performing the test both the antigen and the complement were used in a dose that contained two units of each of them. Thus the use of the complement-fixation test proved instrumental in determining specific complement-fixing antibodies in animals that had recovered from the disease, or animals that had latent infection or had been vaccinated. The titers established usually ranged from 1:2 to 1:8, and in single cases they reached 1:128. On the infected farms some animals presented both complement-fixing and neutralizing antibodies. In Herds with positive reagents was also isolated the virus of bovine rhinotracheitis.", "contents": "[Studies of the complement fixation reaction in infectious rhinotracheitis in cattle]. The complement-fixation reaction was used in the diagnosis of infectious bovine rhinotracheitis establishing its specificity and effectiveness. Highest titers of the antigens tested (up to 1:16) showed antigens that were concentrated with the use of poly ethylene glycol. In performing the test both the antigen and the complement were used in a dose that contained two units of each of them. Thus the use of the complement-fixation test proved instrumental in determining specific complement-fixing antibodies in animals that had recovered from the disease, or animals that had latent infection or had been vaccinated. The titers established usually ranged from 1:2 to 1:8, and in single cases they reached 1:128. On the infected farms some animals presented both complement-fixing and neutralizing antibodies. In Herds with positive reagents was also isolated the virus of bovine rhinotracheitis."} {"id": "PMID:176771", "title": "[Obtaining the beta-globulin fractions from swine and cattle sera and a study of their immunological activity].", "content": "The rivanol precipitation was used to obtain beta-globulin fractions from specific swine sera against edema disease, paratyph and Aujeszky's disease as well as from normal ovine and swine sera. Agar electrophoresis revealed that the preparations produced contained beta-globulin (86 per cent), gamma-globulin (5 per cent), and alpha2-globulin (9 per cent). The beta-globulin preparations were studied for the presence of antibodies against E. coli, Salmonellae, staphylococci, myxovirus parainfluenza-3, adenoviruses, and the virus of Aujeszky's disease. The beta-globulin fraction of the specific serum against edema disease was shown to contain OK and O agglutinizing antibodies against E. coli, having a titer of up to 1:3200, and the gamma-globulin titers of up to 1:12800. The beta-globulin fraction of the specific serum against typhoid contained OH and O agglutinizing antibodies against Salmonella cholerae suis with a titer of up to 1:2560. The agglutinizing antibodies against staphylococci were twice as much in the beta-globulin fraction as compared with those in the gamma-globulin fraction. The antibodies against Aujeszky's disease and the adenoviruses in the beta-globulin fractions were in negligible amounts, and the titer of the antibodies against myxovirus parainfluenza-3 ranged from 1:128 to 1:512.", "contents": "[Obtaining the beta-globulin fractions from swine and cattle sera and a study of their immunological activity]. The rivanol precipitation was used to obtain beta-globulin fractions from specific swine sera against edema disease, paratyph and Aujeszky's disease as well as from normal ovine and swine sera. Agar electrophoresis revealed that the preparations produced contained beta-globulin (86 per cent), gamma-globulin (5 per cent), and alpha2-globulin (9 per cent). The beta-globulin preparations were studied for the presence of antibodies against E. coli, Salmonellae, staphylococci, myxovirus parainfluenza-3, adenoviruses, and the virus of Aujeszky's disease. The beta-globulin fraction of the specific serum against edema disease was shown to contain OK and O agglutinizing antibodies against E. coli, having a titer of up to 1:3200, and the gamma-globulin titers of up to 1:12800. The beta-globulin fraction of the specific serum against typhoid contained OH and O agglutinizing antibodies against Salmonella cholerae suis with a titer of up to 1:2560. The agglutinizing antibodies against staphylococci were twice as much in the beta-globulin fraction as compared with those in the gamma-globulin fraction. The antibodies against Aujeszky's disease and the adenoviruses in the beta-globulin fractions were in negligible amounts, and the titer of the antibodies against myxovirus parainfluenza-3 ranged from 1:128 to 1:512."} {"id": "PMID:176772", "title": "[Early histoenzymologic and ultrastructural changes induced by adrenalin-thyroxine and fat diet in rabbit aorta (author's transl)].", "content": "The first stages of the atherosclerotic lesions induced in the rabbit aorta by adrenalin- thyroxine, with (or without) an hypercholesterolic diet, have been studied on the 6th, 13th, and 22nd day. Major parietal changes, barely demonstrable with light microscopic standard techniques, were detected, as soon as the 6th day, by electronmicroscopy and histoenzymology. These changes were probably due solely to the hormonal treatment. In the early stage, they consisted of some fragmentations of the elastic sheets and some smooth muscle cell lysis. The oxidative and ATPase activities were greatly reduced. The increased lysosomal hydrolase actitivities of the outer layers of the vessel could be related in the increased vascular permeability and consecutive increased perfusion gradient induced by these lesions. Later, an obvious repair process was seen. The smooth muscle cells bearing numerous processes were bound by many microfilaments and by some elastic material. The energetic enzymatic activities were increased. The part taken by the lipidic diet in these changes, apart from the increase of the esterase activity, did not seem yet of significance in this first stage of atherosclerosis. However, one cannot exclude that the intensively accumulating lipids might, at some later stages, potentiate the consequences of the vascular lesions or impede the repair process.", "contents": "[Early histoenzymologic and ultrastructural changes induced by adrenalin-thyroxine and fat diet in rabbit aorta (author's transl)]. The first stages of the atherosclerotic lesions induced in the rabbit aorta by adrenalin- thyroxine, with (or without) an hypercholesterolic diet, have been studied on the 6th, 13th, and 22nd day. Major parietal changes, barely demonstrable with light microscopic standard techniques, were detected, as soon as the 6th day, by electronmicroscopy and histoenzymology. These changes were probably due solely to the hormonal treatment. In the early stage, they consisted of some fragmentations of the elastic sheets and some smooth muscle cell lysis. The oxidative and ATPase activities were greatly reduced. The increased lysosomal hydrolase actitivities of the outer layers of the vessel could be related in the increased vascular permeability and consecutive increased perfusion gradient induced by these lesions. Later, an obvious repair process was seen. The smooth muscle cells bearing numerous processes were bound by many microfilaments and by some elastic material. The energetic enzymatic activities were increased. The part taken by the lipidic diet in these changes, apart from the increase of the esterase activity, did not seem yet of significance in this first stage of atherosclerosis. However, one cannot exclude that the intensively accumulating lipids might, at some later stages, potentiate the consequences of the vascular lesions or impede the repair process."} {"id": "PMID:176773", "title": "[Reduction of oily substances in rabbit lungs (author's transl)].", "content": "Artificial fat embolism in rabbits was caused by injection of olive oil and Lipiodol Ultrafluid into the ear vein. Electron-microscopic and histochemical observations of the lung were made. The content of nonspecific esterase was evaluated. Serious defects of blood vessels and pneumocytes as well as an increase in alveolar macrophages and capillary thrombosis were noted. The endothelial cells became considerably larger and necrosis of endothelial cells and capillary destruction even occurred. Fat appeared interstially and in the alveolus. Tissue reaction is much greater in olive oil than in contrast medium. This is due to their different chemical composition. The strong tissue reaction in olive oil is caused by glycerol and unsaturated fatty acids occurring in hydrolysis. Fat emboli are primarily eliminated by enzymatic splitting. Normally alveolar macrophages and endothelial cells contain little nonspecific esterase. After application of fatty fluids they react with an increase in the content of esterase. Alveolar epithelium seems to participate in enzymatic fat splitting.", "contents": "[Reduction of oily substances in rabbit lungs (author's transl)]. Artificial fat embolism in rabbits was caused by injection of olive oil and Lipiodol Ultrafluid into the ear vein. Electron-microscopic and histochemical observations of the lung were made. The content of nonspecific esterase was evaluated. Serious defects of blood vessels and pneumocytes as well as an increase in alveolar macrophages and capillary thrombosis were noted. The endothelial cells became considerably larger and necrosis of endothelial cells and capillary destruction even occurred. Fat appeared interstially and in the alveolus. Tissue reaction is much greater in olive oil than in contrast medium. This is due to their different chemical composition. The strong tissue reaction in olive oil is caused by glycerol and unsaturated fatty acids occurring in hydrolysis. Fat emboli are primarily eliminated by enzymatic splitting. Normally alveolar macrophages and endothelial cells contain little nonspecific esterase. After application of fatty fluids they react with an increase in the content of esterase. Alveolar epithelium seems to participate in enzymatic fat splitting."} {"id": "PMID:176774", "title": "Pigmentation and dysfunction of Gunn rat thyroid: correlation between morphological and biochemical data.", "content": "The thyroid gland of homozygous Gunn rats is moderately enlarged and displays a brownish-black discoloration. Light microscopic examination discloses that the follicular cells are filled with brown granules, which are shown, under the electron microscope, to be modified colloid droplets. Most of them possess a strong acid phosphatase and a mild peroxidase activity and contain a melanin-like pigment, according to histochemical analysis. In comparison with normal Wistar rats, Gunn rats possess significantly higher plasma thyroxine and lower triiodothyronine as well as an increased plasma TSH level. The soluble protein content of the thyroid is reduced in the Gunn rat, as is the total intrathyroid iodine content. The hyperthyroxinaemia of homozygous Gunn rats is due to a hereditary deficiency in hepatic glucuronyl transferase activity. The excess circulating thyroxine is of little functional importance because it is firmly bound to plasma proteins. But Gunn rats have a slight hypothyroid goitre for reasons not yet elucidated. The functional as well as morphological data at present available suggest a modified thyroid iodine metabolism and an altered composition of the thyroglobulin which may induce abnormalities in colloid proteolysis. The observed pigment may result from peroxidation of tyrosine. These alterations are probably independent of the sole enzymatic deficiency so far encountered in these animals and may probably be ascribed to a primary enzymatic defect in the thyroid gland itself.", "contents": "Pigmentation and dysfunction of Gunn rat thyroid: correlation between morphological and biochemical data. The thyroid gland of homozygous Gunn rats is moderately enlarged and displays a brownish-black discoloration. Light microscopic examination discloses that the follicular cells are filled with brown granules, which are shown, under the electron microscope, to be modified colloid droplets. Most of them possess a strong acid phosphatase and a mild peroxidase activity and contain a melanin-like pigment, according to histochemical analysis. In comparison with normal Wistar rats, Gunn rats possess significantly higher plasma thyroxine and lower triiodothyronine as well as an increased plasma TSH level. The soluble protein content of the thyroid is reduced in the Gunn rat, as is the total intrathyroid iodine content. The hyperthyroxinaemia of homozygous Gunn rats is due to a hereditary deficiency in hepatic glucuronyl transferase activity. The excess circulating thyroxine is of little functional importance because it is firmly bound to plasma proteins. But Gunn rats have a slight hypothyroid goitre for reasons not yet elucidated. The functional as well as morphological data at present available suggest a modified thyroid iodine metabolism and an altered composition of the thyroglobulin which may induce abnormalities in colloid proteolysis. The observed pigment may result from peroxidation of tyrosine. These alterations are probably independent of the sole enzymatic deficiency so far encountered in these animals and may probably be ascribed to a primary enzymatic defect in the thyroid gland itself."} {"id": "PMID:176775", "title": "Mass occurrence of multilamellar bodies in myopathy.", "content": "In a case of atypical myopathy submicroscopic examinations revealed intact ground structure and large number of solitaer, regular multilamellar bodies. The author suggests, in accordance with literary data, this typical alteration to be due to the applied short term Chloroquine treatment.", "contents": "Mass occurrence of multilamellar bodies in myopathy. In a case of atypical myopathy submicroscopic examinations revealed intact ground structure and large number of solitaer, regular multilamellar bodies. The author suggests, in accordance with literary data, this typical alteration to be due to the applied short term Chloroquine treatment."} {"id": "PMID:176776", "title": "Concentric nuclear inclusions.", "content": "Membrane bound concentric lamellar inclusions were found in the nuclei of pancreatic acinar cells of a patient with multiple primary neoplasms and in the parotid acinar cells of a patient with systemic lupus erythematosus. It is proposed that these inclusions form from rough cisternae sequestered in the nucleus.", "contents": "Concentric nuclear inclusions. Membrane bound concentric lamellar inclusions were found in the nuclei of pancreatic acinar cells of a patient with multiple primary neoplasms and in the parotid acinar cells of a patient with systemic lupus erythematosus. It is proposed that these inclusions form from rough cisternae sequestered in the nucleus."} {"id": "PMID:176777", "title": "Glomiform and fibrillar cytoplasmic inclusions.", "content": "Glomiform inclusions, also called tubular arrays in endoplasmic reticulum, are found in the epithelial cells of glandular tissues of a patient with systemic lupus erythematosus, a patient with Reye's syndrome, and a dog. Their three dimensional structure is interpreted as a skein of contorted tubules of endoplasmic reticulum. Fibrillar inclusions found in the pancreatic acinar cells of two patients are believed to represent altered zymogen granules.", "contents": "Glomiform and fibrillar cytoplasmic inclusions. Glomiform inclusions, also called tubular arrays in endoplasmic reticulum, are found in the epithelial cells of glandular tissues of a patient with systemic lupus erythematosus, a patient with Reye's syndrome, and a dog. Their three dimensional structure is interpreted as a skein of contorted tubules of endoplasmic reticulum. Fibrillar inclusions found in the pancreatic acinar cells of two patients are believed to represent altered zymogen granules."} {"id": "PMID:176816", "title": "[The effect of megavolt radiation therapy on glioblastoma multiforme].", "content": "The paper deals with morphological changes in glioblastoma multiforme following megavoltage radiotherapy (1.25 and 25 MeV). Both tumour cell death and glioblastoma multiforme tissue destruction resulted from 6,000-7,500 rads megavoltage irradiation. Depending upon the time following irradiation the histological study showed the prevalance of either acute aseptic inflammation, or coagulation necrosis, or degenerative changes leading to the formation of glial and connective tissue scars and dystrophic calcification. Glioblastoma multiforme, rich in cell elements with hyperchromatic nuclei and having a high mitotic activity, proved to be the most radiosensitive tumour. The highest radioresistance was noted in tumours with a tendency to haemorrhages and necroses.", "contents": "[The effect of megavolt radiation therapy on glioblastoma multiforme]. The paper deals with morphological changes in glioblastoma multiforme following megavoltage radiotherapy (1.25 and 25 MeV). Both tumour cell death and glioblastoma multiforme tissue destruction resulted from 6,000-7,500 rads megavoltage irradiation. Depending upon the time following irradiation the histological study showed the prevalance of either acute aseptic inflammation, or coagulation necrosis, or degenerative changes leading to the formation of glial and connective tissue scars and dystrophic calcification. Glioblastoma multiforme, rich in cell elements with hyperchromatic nuclei and having a high mitotic activity, proved to be the most radiosensitive tumour. The highest radioresistance was noted in tumours with a tendency to haemorrhages and necroses."} {"id": "PMID:176819", "title": "[Synthesis of virus-specific macromolecules and virion maturation in chick embryo cells infected with Sendai virus].", "content": "Synthesis and accumulation of virus-specific RNA, proteins and intracellular nucleocapsids are observed in Sendai virus-infected chick embryo cells for approximately 2 days postinfection. However, only an insignificant part of these products leaves the cell as a result of maturation of virus particles. It is suggested that the cause of the ineffective maturation of virions in the system under study may be in the observed instability of one of virus structural proteins in the infected cells, M protein. Some other suggestions on the mechanisms of nonpermissiveness of paramyxovirus systems expressed in literature earlier are also discussed.", "contents": "[Synthesis of virus-specific macromolecules and virion maturation in chick embryo cells infected with Sendai virus]. Synthesis and accumulation of virus-specific RNA, proteins and intracellular nucleocapsids are observed in Sendai virus-infected chick embryo cells for approximately 2 days postinfection. However, only an insignificant part of these products leaves the cell as a result of maturation of virus particles. It is suggested that the cause of the ineffective maturation of virions in the system under study may be in the observed instability of one of virus structural proteins in the infected cells, M protein. Some other suggestions on the mechanisms of nonpermissiveness of paramyxovirus systems expressed in literature earlier are also discussed."} {"id": "PMID:176821", "title": "[Identification of a hemadsorbing agent discovered in uninfected mouse L cell cultures and also the same cultures chronically infected with Sindbis virus].", "content": "Electron microscope examinations of continuous lines of mouse L cells, both uninfected (L-init) and chronically infected with Sindbis virus (L-SV) revealed accumulations of ribonucleoprotein strands and virions corresponding by their parameters to paramyxoviruses in the cytoplasms of the cells. Further studies showed L-init and L-SV cell lines to have a manifest hemadsorption effect which could be completely inhibited by antiserum to parainfluenza SV5 virus. Immunofluorescence procedures detected intensive fluorescence in the cytoplasm of these cells which was observed only after treatment of the cells with antiserum to SV5 virus. In response to inoculation of cell homogenates of continuous L-init and L-SV cultures guinea pigs developed antihemagglutinating antibody to simian parainfluenza SV5 virus. On the basis of these results it may be assumed that virus-specific structures and viruses identical by their parameters to paramyxoviruses observed in electron microscope examinations of continuous mouse L-init and L-SV cells are simian parainfluenza SV5 virus.", "contents": "[Identification of a hemadsorbing agent discovered in uninfected mouse L cell cultures and also the same cultures chronically infected with Sindbis virus]. Electron microscope examinations of continuous lines of mouse L cells, both uninfected (L-init) and chronically infected with Sindbis virus (L-SV) revealed accumulations of ribonucleoprotein strands and virions corresponding by their parameters to paramyxoviruses in the cytoplasms of the cells. Further studies showed L-init and L-SV cell lines to have a manifest hemadsorption effect which could be completely inhibited by antiserum to parainfluenza SV5 virus. Immunofluorescence procedures detected intensive fluorescence in the cytoplasm of these cells which was observed only after treatment of the cells with antiserum to SV5 virus. In response to inoculation of cell homogenates of continuous L-init and L-SV cultures guinea pigs developed antihemagglutinating antibody to simian parainfluenza SV5 virus. On the basis of these results it may be assumed that virus-specific structures and viruses identical by their parameters to paramyxoviruses observed in electron microscope examinations of continuous mouse L-init and L-SV cells are simian parainfluenza SV5 virus."} {"id": "PMID:176820", "title": "[Protein metabolism in chick embryo cells infected with Sendai virus].", "content": "Inocluation of chick fibroblasts with Sendai virus results in a significant increase of protein synthesis. In cytoplasmic extracts of infected cells the content of polyribosomes increased and that of free (nontranslating) 80S ribosomes decreased, the \"additional\" polysomes of the infected cells being involved in protein synthesis. The portion of virus-specific protein synthesis in the infected cells was about 40% of the total protein synthesis. This means that with the total increase of protein synthesis 2-fold and (in some experiments) higher, the summary synthesis of cell proteins proper is not inhibited (possibly, it is slightly increased). Quite effective synthesis of virus-specific proteins for a comparatively long period after infection and ineffective maturation of virions eventually lead to a rather considerable accumulation of virus-specific proteins in the infected cells. The total content of protein in samples prepared 2 days after infection is approximately 1-1/2 as high as in uninfected samples.", "contents": "[Protein metabolism in chick embryo cells infected with Sendai virus]. Inocluation of chick fibroblasts with Sendai virus results in a significant increase of protein synthesis. In cytoplasmic extracts of infected cells the content of polyribosomes increased and that of free (nontranslating) 80S ribosomes decreased, the \"additional\" polysomes of the infected cells being involved in protein synthesis. The portion of virus-specific protein synthesis in the infected cells was about 40% of the total protein synthesis. This means that with the total increase of protein synthesis 2-fold and (in some experiments) higher, the summary synthesis of cell proteins proper is not inhibited (possibly, it is slightly increased). Quite effective synthesis of virus-specific proteins for a comparatively long period after infection and ineffective maturation of virions eventually lead to a rather considerable accumulation of virus-specific proteins in the infected cells. The total content of protein in samples prepared 2 days after infection is approximately 1-1/2 as high as in uninfected samples."} {"id": "PMID:176829", "title": "[Cytomegalovirus disease in the course of histiocytosis X (AUTHOR'S TRANSL)].", "content": "A 3 1/2 year-old boy was treated with cytostatic drugs for progressive histiocytosis X. 9 months later he acquired cytomegalovirus disease, the diagnosis being proven by liver biopsy. The causal relationship of immunosuppressive side effects of the treatment and this cytomegalovirus infection is discussed.", "contents": "[Cytomegalovirus disease in the course of histiocytosis X (AUTHOR'S TRANSL)]. A 3 1/2 year-old boy was treated with cytostatic drugs for progressive histiocytosis X. 9 months later he acquired cytomegalovirus disease, the diagnosis being proven by liver biopsy. The causal relationship of immunosuppressive side effects of the treatment and this cytomegalovirus infection is discussed."} {"id": "PMID:176830", "title": "[Pseudohypoparathyroidism: investigations of the serum parathyroid hormone level, pte resistance and urinary camp excretion before and during vitamin d treatment (author's transl)].", "content": "Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs, oligophrenia and clinical and laboratory signs of hypoparathyroidism, which is resistant to parathyroid extract (PTE). Pseudopseudohypoparathyroidism (PPHP) is a genetically identical, partial form of PHP without hypoparathyroidism. Many hypotheses exist to explain the pathogenesis of these disorders: Albright and coworkers first demonstrated the PHP is caused by an inability of the renal tubules to respond to parathyroid hormone (PTH). Later hypotheses proposed a general defect in phosphorus transport, defects in the synthesis of PTH, the existence of antibodies to this hormone or hyperthyrocalcitonism. The possibility of measuring PTH in the peripheral serum by radioimmunoassay and improved knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH were necessary to explain the pathogenesis of PHP and PPHP. Three children suffering from PHP and two adults with PPHP were investigated as follows: measurements of PTH in the peripheral serum; assays of PTH levels during artificial hypercalcaemia; serial assays of calcium, phosphorus and PTH levels during vitamin D treatment; changes in the Ellsworth-Howard tests indicative of PTE resistance during vitamin D treatment and measurements of urinary cAMP excretion before and during vitamin D therapy. The following results were obtained: Secondary hyperparathyroidism in PHP, which could be suppressed by hypercalcaemia; normal levels of PTH in PPHP; normalization of serum calcium, phosphorus and PTE during treatment with vitamin D; abnormally low basal levels of cAMP in PHP, which could not be stimulated by PTE either before or during vitamin D treatment. The results of these investigations confirm Albright's hypothesis of endorgan resistance to PTH in PHP. This is caused by the inability of the PTH-sensitive adenylcyclase-system to mediate the action of PTH on its target cells. This is responsible for the distrubances in calcium and phosphorus metabolism and for secondary hyperparathyroidism. While this mediatorial defect seems to be total or almost total in PHP, a partial defect has to be assumed in PPHP.", "contents": "[Pseudohypoparathyroidism: investigations of the serum parathyroid hormone level, pte resistance and urinary camp excretion before and during vitamin d treatment (author's transl)]. Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs, oligophrenia and clinical and laboratory signs of hypoparathyroidism, which is resistant to parathyroid extract (PTE). Pseudopseudohypoparathyroidism (PPHP) is a genetically identical, partial form of PHP without hypoparathyroidism. Many hypotheses exist to explain the pathogenesis of these disorders: Albright and coworkers first demonstrated the PHP is caused by an inability of the renal tubules to respond to parathyroid hormone (PTH). Later hypotheses proposed a general defect in phosphorus transport, defects in the synthesis of PTH, the existence of antibodies to this hormone or hyperthyrocalcitonism. The possibility of measuring PTH in the peripheral serum by radioimmunoassay and improved knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH were necessary to explain the pathogenesis of PHP and PPHP. Three children suffering from PHP and two adults with PPHP were investigated as follows: measurements of PTH in the peripheral serum; assays of PTH levels during artificial hypercalcaemia; serial assays of calcium, phosphorus and PTH levels during vitamin D treatment; changes in the Ellsworth-Howard tests indicative of PTE resistance during vitamin D treatment and measurements of urinary cAMP excretion before and during vitamin D therapy. The following results were obtained: Secondary hyperparathyroidism in PHP, which could be suppressed by hypercalcaemia; normal levels of PTH in PPHP; normalization of serum calcium, phosphorus and PTE during treatment with vitamin D; abnormally low basal levels of cAMP in PHP, which could not be stimulated by PTE either before or during vitamin D treatment. The results of these investigations confirm Albright's hypothesis of endorgan resistance to PTH in PHP. This is caused by the inability of the PTH-sensitive adenylcyclase-system to mediate the action of PTH on its target cells. This is responsible for the distrubances in calcium and phosphorus metabolism and for secondary hyperparathyroidism. While this mediatorial defect seems to be total or almost total in PHP, a partial defect has to be assumed in PPHP."} {"id": "PMID:176822", "title": "[Variants of parainfluenza type 2 viruses].", "content": "A comparative study of the antigenic and biological properties of parainfluenza type 2 viruses revealed the existence of two variants among them. The first variant includes strains isolated up to 1965 inclusive, the 2nd those isolated in 1966--1974. The strains of the 2nd variant are characterized by poor interaction with antibody in immune sera to the reference virus which appears to be due to a loss of one of the antigens in them. Besides, they have comparatively low immunogenicity and the hemagglutinating activity and higher sensitivity to inhibitors. The paper emphasized the necessity of using immune sera to strains isolated in recent years, in addition to reference sera, for identification of new isolated of parainfluenza type 2 virus.", "contents": "[Variants of parainfluenza type 2 viruses]. A comparative study of the antigenic and biological properties of parainfluenza type 2 viruses revealed the existence of two variants among them. The first variant includes strains isolated up to 1965 inclusive, the 2nd those isolated in 1966--1974. The strains of the 2nd variant are characterized by poor interaction with antibody in immune sera to the reference virus which appears to be due to a loss of one of the antigens in them. Besides, they have comparatively low immunogenicity and the hemagglutinating activity and higher sensitivity to inhibitors. The paper emphasized the necessity of using immune sera to strains isolated in recent years, in addition to reference sera, for identification of new isolated of parainfluenza type 2 virus."} {"id": "PMID:176825", "title": "[Sensitivity of normal and Rous virus-transformed lines of Armenian hamster cells to infectious viruses].", "content": "The capacity of normal (NHET) and Rous virus-transformed cell line of armenian hamster both producing (SHET Sh-R) and not producing (SHET K-3) virus to support reproduction of vaccinia and Newcastle disease viruses was demonstrated. The former of these viruses replicated in the cell cultures with cytopathic effect, the latter did so without causing cell degeneration. The degree of Newcastle disease virus reproduction in all 3 cultures was the same whereas vaccinia virus synthesis in SHET Sh-R was inhibited as compared with NHET and SHET K-3 cultures. Interference between Rous virus and vaccinia virus in SHET Sh-R culture was not due to interferon. The infectious viruses under study caused no activation of Rous virus genome in the virogenic SHET K-3 cell line.", "contents": "[Sensitivity of normal and Rous virus-transformed lines of Armenian hamster cells to infectious viruses]. The capacity of normal (NHET) and Rous virus-transformed cell line of armenian hamster both producing (SHET Sh-R) and not producing (SHET K-3) virus to support reproduction of vaccinia and Newcastle disease viruses was demonstrated. The former of these viruses replicated in the cell cultures with cytopathic effect, the latter did so without causing cell degeneration. The degree of Newcastle disease virus reproduction in all 3 cultures was the same whereas vaccinia virus synthesis in SHET Sh-R was inhibited as compared with NHET and SHET K-3 cultures. Interference between Rous virus and vaccinia virus in SHET Sh-R culture was not due to interferon. The infectious viruses under study caused no activation of Rous virus genome in the virogenic SHET K-3 cell line."} {"id": "PMID:176823", "title": "[Recognition of influenza and other acute respiratory virus infections and their combinations by means of immunofluorescence].", "content": "The results of postmortem examinations performed in 237 fatal cases of influenza and other acute respiratory diseases are presented. In smears of organs and tissue culture cells infected with these materials and heart blood the immunofluorescent procedure detected influenza virus antigens in 67% of the cases, antigens of other respiratory viruses in 53% including 18-19% of mixed infections. Parallel immunofluorescent studies in living patients and isolation of influenza virus and adenoviruses increased per cent of influenza case confirmation to 82%, other respiratory infections to 63%. Mixed infection was recorded in 22-28%. Antigens of influenza and parainfluenza viruses were more frequently found in smears of bronchi and trachea, antigens of respiratory syncytial virus and adenovirus in lung smears. Adenovirus antigen was also found in lymphoid cells of smears of the spleen, bronchial lymph node, tonsils. In immunofluorescent examinations of tissue cultures infected with the heart blood, virus antigen was detected most frequently in influenza and adenovirus infection (24% and 26% of cases, respectively), less frequently in respiratory syncytial virus infection (11%) and parainfluenza (5%). Virus antigens were also demonstrated in tissue culture cells infected with specimens of the liver, spleen, bronchial lymph node, tonsils, brain. The immunofluorescent studies demonstrated long-term persistence of virus antigens in the body. In a portion of cases of laboratory confirmed mixed infection there were no clinical-morphological signs of two virus diseases. In these, one of the infections was latent or was due to a previously experienced disease.", "contents": "[Recognition of influenza and other acute respiratory virus infections and their combinations by means of immunofluorescence]. The results of postmortem examinations performed in 237 fatal cases of influenza and other acute respiratory diseases are presented. In smears of organs and tissue culture cells infected with these materials and heart blood the immunofluorescent procedure detected influenza virus antigens in 67% of the cases, antigens of other respiratory viruses in 53% including 18-19% of mixed infections. Parallel immunofluorescent studies in living patients and isolation of influenza virus and adenoviruses increased per cent of influenza case confirmation to 82%, other respiratory infections to 63%. Mixed infection was recorded in 22-28%. Antigens of influenza and parainfluenza viruses were more frequently found in smears of bronchi and trachea, antigens of respiratory syncytial virus and adenovirus in lung smears. Adenovirus antigen was also found in lymphoid cells of smears of the spleen, bronchial lymph node, tonsils. In immunofluorescent examinations of tissue cultures infected with the heart blood, virus antigen was detected most frequently in influenza and adenovirus infection (24% and 26% of cases, respectively), less frequently in respiratory syncytial virus infection (11%) and parainfluenza (5%). Virus antigens were also demonstrated in tissue culture cells infected with specimens of the liver, spleen, bronchial lymph node, tonsils, brain. The immunofluorescent studies demonstrated long-term persistence of virus antigens in the body. In a portion of cases of laboratory confirmed mixed infection there were no clinical-morphological signs of two virus diseases. In these, one of the infections was latent or was due to a previously experienced disease."} {"id": "PMID:176824", "title": "[Study of the population composition of the Rous sarcoma virus Carr-Zilber strain].", "content": "The population composition of the Carr-Zilber high titer (HT) strain of Rous sarcoma virus (C-Z-RSV) was analysed with regard to 2 features: the capacity to impart oncogenicity for syngeneic recipients to infected but untransformed cultures of mouse embryo tissue (MET), and oncogenicity for mice. With regard to these features the C-Z-RSV (HT) strain was found to be heterogenic and to consist of particles of at least two types: non-oncogenic for mice and incapable of causing early malignization of MET, and oncogenic for mice and causing early malignization.", "contents": "[Study of the population composition of the Rous sarcoma virus Carr-Zilber strain]. The population composition of the Carr-Zilber high titer (HT) strain of Rous sarcoma virus (C-Z-RSV) was analysed with regard to 2 features: the capacity to impart oncogenicity for syngeneic recipients to infected but untransformed cultures of mouse embryo tissue (MET), and oncogenicity for mice. With regard to these features the C-Z-RSV (HT) strain was found to be heterogenic and to consist of particles of at least two types: non-oncogenic for mice and incapable of causing early malignization of MET, and oncogenic for mice and causing early malignization."} {"id": "PMID:176836", "title": "Histochemistry and histoenzymology of the hydatid cyst (Echinococcus granulosus Batsch, 1786). I. The germinal membrane.", "content": "Healthy germinal membranes of hydatid cysts from lungs of human and bovine sources were dissected and isolated for histochemical and histoenzymatic research. These techniques were performed in frozen sections and pieces of the whole membrane. Enzymatic research showed that the germinal membrane presents highly differentiated metabolic areas. These areas were topographically related with the origin and insertion of brood capsules, having differentiated structures for metabolic interchange with scolices. Taking our data into account it may be suggested that this functional differentiation could be transitory and variable for all the membrane surface. The accumulation of lipids and enzymes such as simple estarase, lipase, beta-HDH, alpha-GDH and NADPH-reductase in those areas, suggests that lipids are not a simple excretory product. This distribution probably implies that lipid metabolism or its resultant products are important in development and growth of scolices. In that sense other authors' findings and hypothesis about the possible existence of an endocrine system of the parasite, are considered. This idea being demonstrated in further researches, the lipid metabolic pathways shall bring a good pharmacological approach to the interference with parasite development.", "contents": "Histochemistry and histoenzymology of the hydatid cyst (Echinococcus granulosus Batsch, 1786). I. The germinal membrane. Healthy germinal membranes of hydatid cysts from lungs of human and bovine sources were dissected and isolated for histochemical and histoenzymatic research. These techniques were performed in frozen sections and pieces of the whole membrane. Enzymatic research showed that the germinal membrane presents highly differentiated metabolic areas. These areas were topographically related with the origin and insertion of brood capsules, having differentiated structures for metabolic interchange with scolices. Taking our data into account it may be suggested that this functional differentiation could be transitory and variable for all the membrane surface. The accumulation of lipids and enzymes such as simple estarase, lipase, beta-HDH, alpha-GDH and NADPH-reductase in those areas, suggests that lipids are not a simple excretory product. This distribution probably implies that lipid metabolism or its resultant products are important in development and growth of scolices. In that sense other authors' findings and hypothesis about the possible existence of an endocrine system of the parasite, are considered. This idea being demonstrated in further researches, the lipid metabolic pathways shall bring a good pharmacological approach to the interference with parasite development."} {"id": "PMID:176837", "title": "Freeze-etching observations of trophozoites of pathogenic Entamoeba histolytica.", "content": "Pathogenic Entamoeba histolytica trophozoites were studied by the freeze-etching (FE) technique of electron microscopy. Surface replicas of intact cell membranes were highly convoluted with numerous invaginations, evaginations, and undulations. Sperical depressions and elevations varying from 0.5 mu to 1.0 mu in diameter were commonly present on the external cell membrane and appeared to represent an extracellular secretory mechanism of trophozoites. Cleaved surfaces of amebae exhibited a granular and lumpy cytoplasm in which there were many vesicles and vacuoles that ranged in diameter from 0.2 mu to 9.0 mu. Some vacuoles contained tightly enveloped bacteria, while others contained bacteria and host cytocomponents. Occasional vesicles and vacuoles appeared to be fused to each other. Replicas of FE nucleus were enclosed by double nuclear membranes which were fenestrated by numerous sperical pores measuring approximately 640 A in diameter and spaced at intervals of 650 A. Counts of nuclear pores were possible and indicated 35 pores per square micron on the nuclear envelope. Golgi apparatus, mitochondria and well formed endoplasmic reticulum were absent in FE replicas. This was in agreement with electron microscope observations on thin sections previously reported by other investigators.", "contents": "Freeze-etching observations of trophozoites of pathogenic Entamoeba histolytica. Pathogenic Entamoeba histolytica trophozoites were studied by the freeze-etching (FE) technique of electron microscopy. Surface replicas of intact cell membranes were highly convoluted with numerous invaginations, evaginations, and undulations. Sperical depressions and elevations varying from 0.5 mu to 1.0 mu in diameter were commonly present on the external cell membrane and appeared to represent an extracellular secretory mechanism of trophozoites. Cleaved surfaces of amebae exhibited a granular and lumpy cytoplasm in which there were many vesicles and vacuoles that ranged in diameter from 0.2 mu to 9.0 mu. Some vacuoles contained tightly enveloped bacteria, while others contained bacteria and host cytocomponents. Occasional vesicles and vacuoles appeared to be fused to each other. Replicas of FE nucleus were enclosed by double nuclear membranes which were fenestrated by numerous sperical pores measuring approximately 640 A in diameter and spaced at intervals of 650 A. Counts of nuclear pores were possible and indicated 35 pores per square micron on the nuclear envelope. Golgi apparatus, mitochondria and well formed endoplasmic reticulum were absent in FE replicas. This was in agreement with electron microscope observations on thin sections previously reported by other investigators."} {"id": "PMID:176843", "title": "[Application of a demographic method for the study of adenoviruses and herpesviruses in a closed infantile community (author's transl)].", "content": "Rate of seroconversions to adenoviruses, cytomegaloviruses (CMV) and Epstein-Barr virus (EBV) was studied from 1965-1973 in 200 infants living in a closed infantile community. The transversal demographic table method was used to evaluate the results of sera examined. Seroconversion occurs earlier in the case of adenoviruses with also possess in higher intensity of infection. The intensity of seroconversions to EBV capsid antigen is a little lower, but of all three viruses examined, the spreading of infection is the slowest. On the other hand, seroconversion to CMV occurs earlier than EBV capsid antigen, but intensity of infection by this virus is lowest.", "contents": "[Application of a demographic method for the study of adenoviruses and herpesviruses in a closed infantile community (author's transl)]. Rate of seroconversions to adenoviruses, cytomegaloviruses (CMV) and Epstein-Barr virus (EBV) was studied from 1965-1973 in 200 infants living in a closed infantile community. The transversal demographic table method was used to evaluate the results of sera examined. Seroconversion occurs earlier in the case of adenoviruses with also possess in higher intensity of infection. The intensity of seroconversions to EBV capsid antigen is a little lower, but of all three viruses examined, the spreading of infection is the slowest. On the other hand, seroconversion to CMV occurs earlier than EBV capsid antigen, but intensity of infection by this virus is lowest."} {"id": "PMID:176841", "title": "[Study of the behavior of poliomyelitis virus type 1 in diffrerent hydrous media (author's transl)].", "content": "After having analyzed several surveys on natural inactivation of viruses in water, the authors have attempted to determine the survival life of poliomyelitis virus type 1 in hydrous medium, of known composition, well-buffered and devoid of any bacterial contamination on the one hand, and on the other hand, in a similar medium with addition of organic humate-type substances. The experiment was carried out at 4 degrees C and at laboratory room temperature (18 degrees C-24 degrees C). Results tend to confirm that the presence of humate-type substances seems to have no significant influence on the development of poliomyelitis virus type 1. Moreover, under the experimental conditions used, the survival life of the virus is much longer than the one previously described. It represents an average of 296 days for a storage temperature of 18 degrees C-24 degrees C. It is longer in water kept at 4 degrees C; in fact, according to statistical calculations and to titrations carried out over a period of 550 days, the total disappearance of the virus was detected only after a period of 10 to 15 years.", "contents": "[Study of the behavior of poliomyelitis virus type 1 in diffrerent hydrous media (author's transl)]. After having analyzed several surveys on natural inactivation of viruses in water, the authors have attempted to determine the survival life of poliomyelitis virus type 1 in hydrous medium, of known composition, well-buffered and devoid of any bacterial contamination on the one hand, and on the other hand, in a similar medium with addition of organic humate-type substances. The experiment was carried out at 4 degrees C and at laboratory room temperature (18 degrees C-24 degrees C). Results tend to confirm that the presence of humate-type substances seems to have no significant influence on the development of poliomyelitis virus type 1. Moreover, under the experimental conditions used, the survival life of the virus is much longer than the one previously described. It represents an average of 296 days for a storage temperature of 18 degrees C-24 degrees C. It is longer in water kept at 4 degrees C; in fact, according to statistical calculations and to titrations carried out over a period of 550 days, the total disappearance of the virus was detected only after a period of 10 to 15 years."} {"id": "PMID:176845", "title": "[Virucidal activity of the disinfectant \"gigasept\" against different enveloped and non-enveloped RNA-and DNA-viruses, pathogenic for men. I. Investigation in the suspension test (author's transl)].", "content": "\"Gigasept\" is a highly efficient chemical disinfectant on the basis of succine dialdehyde and form aldehyde. The virucidal capacity was assayed in the suspension test procedure with different representative RNA and DNA viruses with and without an envelope, such as polio wild virus type I, coxsackie virus type B 3, adeno virus type 3, herpes virus type ) and vaccinia virus. Parameter for disinfectant activity was the virus inactivation kinetic, i. e. interdependence of titer reduction vs. disinfectant concentration and disinfectant contact time. A \"minimal disinfection\" was defined as a greater than or equal to 99.9% virus inactivation. A \"disinfection per definitionem\" must gain a titer reduction of greater than or equal to 10(3) ID 50 and absence of virus. According to these criteria all virus strains were inactivated by Gigasept regardless of absence or presence of serum, which was tested in a concentration of 40% calf serum. Disinfection per definitionem was achieved with Gigasept concentrations of 3% after 60 min. or 5% after 30 min. except for enteroviruses. This group of viruses has to be disinfected with a 10% solution for 4 hours or with a 5% solution overnight. Gigasept, on the basis of these results, can be classified as a highly effective virucidal disinfectant. As to the hepatitis virus group however, no data so far are available. An enterovirus - disinfection procedure is recommended in hepatitis risk areas, as long as test systems for hepatitis viruses are not developed.", "contents": "[Virucidal activity of the disinfectant \"gigasept\" against different enveloped and non-enveloped RNA-and DNA-viruses, pathogenic for men. I. Investigation in the suspension test (author's transl)]. \"Gigasept\" is a highly efficient chemical disinfectant on the basis of succine dialdehyde and form aldehyde. The virucidal capacity was assayed in the suspension test procedure with different representative RNA and DNA viruses with and without an envelope, such as polio wild virus type I, coxsackie virus type B 3, adeno virus type 3, herpes virus type ) and vaccinia virus. Parameter for disinfectant activity was the virus inactivation kinetic, i. e. interdependence of titer reduction vs. disinfectant concentration and disinfectant contact time. A \"minimal disinfection\" was defined as a greater than or equal to 99.9% virus inactivation. A \"disinfection per definitionem\" must gain a titer reduction of greater than or equal to 10(3) ID 50 and absence of virus. According to these criteria all virus strains were inactivated by Gigasept regardless of absence or presence of serum, which was tested in a concentration of 40% calf serum. Disinfection per definitionem was achieved with Gigasept concentrations of 3% after 60 min. or 5% after 30 min. except for enteroviruses. This group of viruses has to be disinfected with a 10% solution for 4 hours or with a 5% solution overnight. Gigasept, on the basis of these results, can be classified as a highly effective virucidal disinfectant. As to the hepatitis virus group however, no data so far are available. An enterovirus - disinfection procedure is recommended in hepatitis risk areas, as long as test systems for hepatitis viruses are not developed."} {"id": "PMID:176842", "title": "[Cytomegalovirus antibodies in the pregnant female and in the newborn infant complement fixation and indirect hemagglutination tests (author's transl)].", "content": "705 paired sera from mother and infant have been studied at the time of the child birth for the presence of cytomegalovirus antibodies by complement-fixation and indirect hemagglutination tests. 51.3% of those sera were found to have CF antibodies, and 72.8% to have HA antibodies. The indirect hemagglutination test is a more sensitive reaction and detects also IgM antibodies. Chosen sera were fractionated and searched for IgM-HA antibodies to detect CMV congenital infections; only one child was found to be positive. The number of mothers having been in contact with cytomegalovirus was 82.7% (having CF or HA antibodies or both). Immigrant were found to be more often positive than native women (94.3% vs 76.1%); this difference was even greater when CF antibodies alone were considered (74.6% vs 37.7%). Depending on age groups of mothers, the increased number of positives found in CF test was not noticed in HA test.", "contents": "[Cytomegalovirus antibodies in the pregnant female and in the newborn infant complement fixation and indirect hemagglutination tests (author's transl)]. 705 paired sera from mother and infant have been studied at the time of the child birth for the presence of cytomegalovirus antibodies by complement-fixation and indirect hemagglutination tests. 51.3% of those sera were found to have CF antibodies, and 72.8% to have HA antibodies. The indirect hemagglutination test is a more sensitive reaction and detects also IgM antibodies. Chosen sera were fractionated and searched for IgM-HA antibodies to detect CMV congenital infections; only one child was found to be positive. The number of mothers having been in contact with cytomegalovirus was 82.7% (having CF or HA antibodies or both). Immigrant were found to be more often positive than native women (94.3% vs 76.1%); this difference was even greater when CF antibodies alone were considered (74.6% vs 37.7%). Depending on age groups of mothers, the increased number of positives found in CF test was not noticed in HA test."} {"id": "PMID:176844", "title": "[The potentiating effects of azathioprine and azapropazone on the enzyme activity in experimental inflammation].", "content": "The influence of prednisolone, azathioprine, and azapropazone on the activity of collagen peptidase, acid phosphatase (complete), and the lactate dehydrogenase of granulation tissue was studied using a model of proliferative inflammation i.e. the cotton-granuloma in rats. The authors observed significant decreases in the activities of the collagen peptidase and acid phosphatase during treatment with prednisone and under combined treatment with azathioprine and azapropazone. In contrast, administration of either azathioprine or azapropazone by itself caused no changes in these enzyme activities as compared with a control group. These studies suggest that the last mentioned drugs potentiate each other in their inhibiting effect upon these enzyme activities. Whether or not these findings are of importance in the clinical treatment of chronic bacterial inflammations must be studied in further trials.", "contents": "[The potentiating effects of azathioprine and azapropazone on the enzyme activity in experimental inflammation]. The influence of prednisolone, azathioprine, and azapropazone on the activity of collagen peptidase, acid phosphatase (complete), and the lactate dehydrogenase of granulation tissue was studied using a model of proliferative inflammation i.e. the cotton-granuloma in rats. The authors observed significant decreases in the activities of the collagen peptidase and acid phosphatase during treatment with prednisone and under combined treatment with azathioprine and azapropazone. In contrast, administration of either azathioprine or azapropazone by itself caused no changes in these enzyme activities as compared with a control group. These studies suggest that the last mentioned drugs potentiate each other in their inhibiting effect upon these enzyme activities. Whether or not these findings are of importance in the clinical treatment of chronic bacterial inflammations must be studied in further trials."} {"id": "PMID:176851", "title": "[Method of determinating the protective capacity of C1. perfringens toxoid].", "content": "The authors describe a model of experimental gas gangrene in guinea pigs; it was produced by the administration of the vegetative form of C. perfringens; the cells were completely washed of the lethal toxin and no toxic or necrotizing agents were added. A possibility of development of gangrenous process without any preliminary depression of the resistance of body tissues in the area of injection of the causative agent was revealed. Apart from the local process and general intoxication gas gangrene, caused by intramuscular injection of C1. perfringens to guinea pigs, was accompanied by bacteriemia and microbial contamination of the internal organs. A method of the animal infection was ascertained and the causes of their death was assessed. The method is recommended for determination of the immunological efficacy of C1. perfringens toxoids.", "contents": "[Method of determinating the protective capacity of C1. perfringens toxoid]. The authors describe a model of experimental gas gangrene in guinea pigs; it was produced by the administration of the vegetative form of C. perfringens; the cells were completely washed of the lethal toxin and no toxic or necrotizing agents were added. A possibility of development of gangrenous process without any preliminary depression of the resistance of body tissues in the area of injection of the causative agent was revealed. Apart from the local process and general intoxication gas gangrene, caused by intramuscular injection of C1. perfringens to guinea pigs, was accompanied by bacteriemia and microbial contamination of the internal organs. A method of the animal infection was ascertained and the causes of their death was assessed. The method is recommended for determination of the immunological efficacy of C1. perfringens toxoids."} {"id": "PMID:176854", "title": "[Restoration of the automatic contractile activity of K+-arrested heart muscle cells in culture by means of dibutyryl-3', 5'-adenosine monophosphate].", "content": "Cultured myocardial cells of new-born rats which were arrested by 17.6-37.6 mM KCl regained their ability to contract spontaneously after perfusion with 8-10(-4)-4-10(-3) M dibutyryl cyclic AMP. This adrenaline-like action of DbcAMP is compatible with the notion that cyclic AMP is involved as a second messenger in the action of cyclic AMP-raising adrenergic agents on cardiac activity.", "contents": "[Restoration of the automatic contractile activity of K+-arrested heart muscle cells in culture by means of dibutyryl-3', 5'-adenosine monophosphate]. Cultured myocardial cells of new-born rats which were arrested by 17.6-37.6 mM KCl regained their ability to contract spontaneously after perfusion with 8-10(-4)-4-10(-3) M dibutyryl cyclic AMP. This adrenaline-like action of DbcAMP is compatible with the notion that cyclic AMP is involved as a second messenger in the action of cyclic AMP-raising adrenergic agents on cardiac activity."} {"id": "PMID:176855", "title": "Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells.", "content": "Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [14C] and [3H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer.", "contents": "Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells. Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [14C] and [3H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer."} {"id": "PMID:176856", "title": "Utilization of dehydroepiandrosterone and its sulphate for oestrogen production by pregnant baboons (Papio papio).", "content": "The effect of varying maternal circulating 3beta-hydroxy-5-androsten-17-one (D) and its sulphate (DS) on urinary oestrogen (Oe) excretion by baboons was determined between 65 and 174 days gestation (term = 184 days). Oe (mainly oestrone) was determined by radioimmunoassay after enzymic hydrolysis of conjugates. Increments in Oe were estimated from the difference between Oe during 5 days pre- and post-treatment. Oestradiol-17beta (5 mg in 5.0 ml saline-ethanol, 1:1) administered iv increased (P less than 0.001) Oe by 2.46 +/- 0.71, 7 (mean, mg +/- SD, number of experiments). The response to 100 mg D (3.20 +/- 1.50, 7) was greater (P less than 0.001) than that due to 100 mg DS (0.03 +/- 0.75, 7). The response to DS was not different from that due to saline-ethanol alone (-0.05 +/- 0.27, 5). Betamethasone (9alpha-fluoro-11beta,17,21-trihydroxy-16beta-methyl-1,4-pregnadiene-3,20-dione) administration (3 mg bi-daily, im) caused an approximately 90% reduction in Oe within 4 days. In animals treated chronically with betamethasone the response due to 100 mg D (2.74 +/- 1.04, 5) was again greater (P less than 0.001) that that due to 100 mg DS (0.10 +/- 0.09, 5). ACTH (8 U or 40 U, im, N = 11) produced a variable but not significant mean change in Oe at either dose level. Metyrapone (300 mg every 4 h for 6 doses) increased (P less than 0.005) Oe (0.77 +/- 0.48, 5). It is concluded that in normal pregnant animals and those treated with betamethasone, in which endogenous levels of D and DS are presumably reduced, D is preferentially used over DS for oestrogen produced. Variations in DS availability do not produce marked changes in oestrogen production. This suggest that rapid increases in oestrogen production, as occur for example close to term, may result from increased availability of D rather than DS. The variable responses to ACTH and the increase in Oe following metyrapone administration are compatible with significant foetal contributions of oestrogen precursors, the production of which is under ACTH control.", "contents": "Utilization of dehydroepiandrosterone and its sulphate for oestrogen production by pregnant baboons (Papio papio). The effect of varying maternal circulating 3beta-hydroxy-5-androsten-17-one (D) and its sulphate (DS) on urinary oestrogen (Oe) excretion by baboons was determined between 65 and 174 days gestation (term = 184 days). Oe (mainly oestrone) was determined by radioimmunoassay after enzymic hydrolysis of conjugates. Increments in Oe were estimated from the difference between Oe during 5 days pre- and post-treatment. Oestradiol-17beta (5 mg in 5.0 ml saline-ethanol, 1:1) administered iv increased (P less than 0.001) Oe by 2.46 +/- 0.71, 7 (mean, mg +/- SD, number of experiments). The response to 100 mg D (3.20 +/- 1.50, 7) was greater (P less than 0.001) than that due to 100 mg DS (0.03 +/- 0.75, 7). The response to DS was not different from that due to saline-ethanol alone (-0.05 +/- 0.27, 5). Betamethasone (9alpha-fluoro-11beta,17,21-trihydroxy-16beta-methyl-1,4-pregnadiene-3,20-dione) administration (3 mg bi-daily, im) caused an approximately 90% reduction in Oe within 4 days. In animals treated chronically with betamethasone the response due to 100 mg D (2.74 +/- 1.04, 5) was again greater (P less than 0.001) that that due to 100 mg DS (0.10 +/- 0.09, 5). ACTH (8 U or 40 U, im, N = 11) produced a variable but not significant mean change in Oe at either dose level. Metyrapone (300 mg every 4 h for 6 doses) increased (P less than 0.005) Oe (0.77 +/- 0.48, 5). It is concluded that in normal pregnant animals and those treated with betamethasone, in which endogenous levels of D and DS are presumably reduced, D is preferentially used over DS for oestrogen produced. Variations in DS availability do not produce marked changes in oestrogen production. This suggest that rapid increases in oestrogen production, as occur for example close to term, may result from increased availability of D rather than DS. The variable responses to ACTH and the increase in Oe following metyrapone administration are compatible with significant foetal contributions of oestrogen precursors, the production of which is under ACTH control."} {"id": "PMID:176857", "title": "Effect of prolactin, growth hormone and insulin on the uptake and binding of dihydrotestosterone to the cultured rat ventral prostate.", "content": "The effects of prolactin, growth hormone and insulin on the total uptake and specific binding of tritiated dihydrotestosterone in the cultured rat ventral prostate were examined. In similiar conditions prolactin and insulin act synergistically with testosterone on the macromolecule synthesis of the prostate, but have no effect on the conversion of testosterone to dihydrotestosterone. The total uptake of tritiated dihydrotestosterone to the tissues was slightly, but not statistically significantly, increased by prolactin, insulin and growth hormone. The majority of the radioactive dihydrotestosterone in the tissue was in free form or very loosely bound. None of these three hormones altered the binding of tritiated dihydrostestosterone to the cytoplasmic receptors. Non-radioactive dihydrotestosterone, cyproterone and cyproterone acetate in 1000 fold excess strongly decreased the binding of tritiated dihydrotestosterone to the cytoplasmic reseptors and to the nuclei. That part of the binding, which was inhibited by the hormones was considered to represent the specific binding to the receptors. Insulin stimulated both the specific and the unspecific uptake of dihydrostestosterone to the nuclei. Prolactin only stimulated the specific uptake to the nuclei while growth hormone had no effect. Autoradiography of the nuclear fraction indicated a firm binding of tritiated dihydrotestosterone to the nuclei. The radioactivity of the other contaminating cell components in this fraction appeared to be negligible.", "contents": "Effect of prolactin, growth hormone and insulin on the uptake and binding of dihydrotestosterone to the cultured rat ventral prostate. The effects of prolactin, growth hormone and insulin on the total uptake and specific binding of tritiated dihydrotestosterone in the cultured rat ventral prostate were examined. In similiar conditions prolactin and insulin act synergistically with testosterone on the macromolecule synthesis of the prostate, but have no effect on the conversion of testosterone to dihydrotestosterone. The total uptake of tritiated dihydrotestosterone to the tissues was slightly, but not statistically significantly, increased by prolactin, insulin and growth hormone. The majority of the radioactive dihydrotestosterone in the tissue was in free form or very loosely bound. None of these three hormones altered the binding of tritiated dihydrostestosterone to the cytoplasmic receptors. Non-radioactive dihydrotestosterone, cyproterone and cyproterone acetate in 1000 fold excess strongly decreased the binding of tritiated dihydrotestosterone to the cytoplasmic reseptors and to the nuclei. That part of the binding, which was inhibited by the hormones was considered to represent the specific binding to the receptors. Insulin stimulated both the specific and the unspecific uptake of dihydrostestosterone to the nuclei. Prolactin only stimulated the specific uptake to the nuclei while growth hormone had no effect. Autoradiography of the nuclear fraction indicated a firm binding of tritiated dihydrotestosterone to the nuclei. The radioactivity of the other contaminating cell components in this fraction appeared to be negligible."} {"id": "PMID:176858", "title": "Infectious mononucleosis in a patient with Hodgkin's disease.", "content": "The case is presented of a patient, treated for Hodgkin's disease, who contracted infectious mononucleosis more than 3 years later. While Epstein-Barr virus has been considered a possible etiologic factor in Hodgkin's disease, the sequence of events reported in this case has to be interpreted as evidence against a causal relationship between the virus and Hodgkin's disease in this patient.", "contents": "Infectious mononucleosis in a patient with Hodgkin's disease. The case is presented of a patient, treated for Hodgkin's disease, who contracted infectious mononucleosis more than 3 years later. While Epstein-Barr virus has been considered a possible etiologic factor in Hodgkin's disease, the sequence of events reported in this case has to be interpreted as evidence against a causal relationship between the virus and Hodgkin's disease in this patient."} {"id": "PMID:176859", "title": "Cytochemical leukocyte reactions in normal children.", "content": "Five cytochemical reactions in current use (MPO, PAS, LAP, SB and EST) were operated on 180 children aged 1 month to 6 years, divided into three age groups (less than 12 months, 1-3 years and 3-6 years). No significant differences are apparent from one group to another, and the mean values are identical with those of adults. On the other hand, certain variations are evident in comparison with the scores of newborn children: important decrease in LAP, increase in SB, EST and PAS. These tests should be done in investigations of inborn metabolic errors, chromosome anomalies, blood diseases, and defects in defense mechanisms.", "contents": "Cytochemical leukocyte reactions in normal children. Five cytochemical reactions in current use (MPO, PAS, LAP, SB and EST) were operated on 180 children aged 1 month to 6 years, divided into three age groups (less than 12 months, 1-3 years and 3-6 years). No significant differences are apparent from one group to another, and the mean values are identical with those of adults. On the other hand, certain variations are evident in comparison with the scores of newborn children: important decrease in LAP, increase in SB, EST and PAS. These tests should be done in investigations of inborn metabolic errors, chromosome anomalies, blood diseases, and defects in defense mechanisms."} {"id": "PMID:176860", "title": "Malignant mixed tumor of the liver: report of a case and a review of the literature.", "content": "Malignant mixed tumor of the liver seen in a 4 year old girl was reported. Progressive hepatomegaly, jaundice, anemia, and extraordinarily high level of serum total cholesterol were noted clinically. Postmortem examination had disclosed that most part of the tumor was occupied by fibrosarcomatous cell growth admixed with rhabdomyosarcomatous component. In addition, carcinomatous component was distinctly recognized in a restricted part of the liver tumor. Previous reports on malignant mixed tumor of the liver were reviewed and it was emphasized that the histological diagnosis of malignant hepatic mixed tumor must be cautiously followed Edmondson's criteria; which requires existence of both epithelial and mesenchymal components of neoplastic nature and malignancy of either or both components in a hepatic tumor.", "contents": "Malignant mixed tumor of the liver: report of a case and a review of the literature. Malignant mixed tumor of the liver seen in a 4 year old girl was reported. Progressive hepatomegaly, jaundice, anemia, and extraordinarily high level of serum total cholesterol were noted clinically. Postmortem examination had disclosed that most part of the tumor was occupied by fibrosarcomatous cell growth admixed with rhabdomyosarcomatous component. In addition, carcinomatous component was distinctly recognized in a restricted part of the liver tumor. Previous reports on malignant mixed tumor of the liver were reviewed and it was emphasized that the histological diagnosis of malignant hepatic mixed tumor must be cautiously followed Edmondson's criteria; which requires existence of both epithelial and mesenchymal components of neoplastic nature and malignancy of either or both components in a hepatic tumor."} {"id": "PMID:176861", "title": "Hormone-induced diarrhea in man.", "content": "In a healthy subject infusions of either secretion or glucagon caused no diarrhea. A combinations of gastrin and glucagon induced severe watery diarrhea immediately after the end of the 3 hour infusion. No diarrhea occurred from the combination of secretin and gastrin.", "contents": "Hormone-induced diarrhea in man. In a healthy subject infusions of either secretion or glucagon caused no diarrhea. A combinations of gastrin and glucagon induced severe watery diarrhea immediately after the end of the 3 hour infusion. No diarrhea occurred from the combination of secretin and gastrin."} {"id": "PMID:176864", "title": "SV 40 related papova-viruses in human meningiomas.", "content": "Human meningiomas show characteristic chromosome aberrations very similar to those reported in human cell cultures experimentally transformed by Simian virus 40 (SV 40). Three out of eight meningiomas tested showed SV 40 specific tumor antigen but no virus capsid antigen. Experiments to rescue virus were successfully performed. Electron microscopic studies of these cell cultures revealed cytoplasmic inclusions containing virus particles which corresponded in size and morphology to Papova viruses.", "contents": "SV 40 related papova-viruses in human meningiomas. Human meningiomas show characteristic chromosome aberrations very similar to those reported in human cell cultures experimentally transformed by Simian virus 40 (SV 40). Three out of eight meningiomas tested showed SV 40 specific tumor antigen but no virus capsid antigen. Experiments to rescue virus were successfully performed. Electron microscopic studies of these cell cultures revealed cytoplasmic inclusions containing virus particles which corresponded in size and morphology to Papova viruses."} {"id": "PMID:176865", "title": "Further observations on the effects of lead implantation in rat brains.", "content": "Lead pellets were implanted into the forebrains of adult rats. Various cytoplasmic inclusions were found in macrophages, astrocytes, pericytes and microglia. Certain macrophages and reactive astrocytes displayed intranuclear inclusions as well. The hypothalamus, in some of the animals, showed sponginess which proved to be the result of swollen axons.", "contents": "Further observations on the effects of lead implantation in rat brains. Lead pellets were implanted into the forebrains of adult rats. Various cytoplasmic inclusions were found in macrophages, astrocytes, pericytes and microglia. Certain macrophages and reactive astrocytes displayed intranuclear inclusions as well. The hypothalamus, in some of the animals, showed sponginess which proved to be the result of swollen axons."} {"id": "PMID:176866", "title": "Plasma lipids and lipoproteins in protein-calorie malnutrition.", "content": "Plasma triglycerides, phospholipids and total cholesterol estimations and lipoprotein electrophoresis on agarose gel were done in control, Kwashiorkor, and marasmic kwashiorkor children. The beta lipoprotein percentage in both conditions is reduced to a statistically significant extent, whereas there is a statistically significant increase in plasma triglycerides in both conditions. Pre-beta fraction was present in all cases, and even increased in marasmic kwashiorkor, which is found to be significant. The results do not support the hypothesis that fatty liver in kwashiorkor is due to impaired release of triglycerides from liver.", "contents": "Plasma lipids and lipoproteins in protein-calorie malnutrition. Plasma triglycerides, phospholipids and total cholesterol estimations and lipoprotein electrophoresis on agarose gel were done in control, Kwashiorkor, and marasmic kwashiorkor children. The beta lipoprotein percentage in both conditions is reduced to a statistically significant extent, whereas there is a statistically significant increase in plasma triglycerides in both conditions. Pre-beta fraction was present in all cases, and even increased in marasmic kwashiorkor, which is found to be significant. The results do not support the hypothesis that fatty liver in kwashiorkor is due to impaired release of triglycerides from liver."} {"id": "PMID:176867", "title": "Two cases of phosphoenolpyruvate carboxykinase deficiency.", "content": "Two children are described who suffered from hypoglycemia and liver impairment. Assays of gluconeogenic enzymes in liver samples taken immediately after death demonstrated a deficiency of phosphoenolpyruvate carboxykinase, a key enzyme of gluconeogenesis. Post mortem examination demonstrated massive fat deposition in liver and kidney and to a lesser extent in other tissues. The fatty changes in liver and kidney could be explained by the absence of phosphoenolpyruvate carboxykinase, which would cause an alteration in the mitochondrial-cytosolic processes related to gluconeogenesis.", "contents": "Two cases of phosphoenolpyruvate carboxykinase deficiency. Two children are described who suffered from hypoglycemia and liver impairment. Assays of gluconeogenic enzymes in liver samples taken immediately after death demonstrated a deficiency of phosphoenolpyruvate carboxykinase, a key enzyme of gluconeogenesis. Post mortem examination demonstrated massive fat deposition in liver and kidney and to a lesser extent in other tissues. The fatty changes in liver and kidney could be explained by the absence of phosphoenolpyruvate carboxykinase, which would cause an alteration in the mitochondrial-cytosolic processes related to gluconeogenesis."} {"id": "PMID:176868", "title": "Effects of viral and mycoplasma infections on ultrastructure and enzyme activities in human skeletal muscle.", "content": "The effect on skeletal muscle of acute viral and mycoplasma infections in thirteen men of ages ranging between 20-42 years has been studied. Comparisons are made with eight healthy men in the age group 22-29 years who were confined to bed for periods of time of lengths similar to the confinement to bed of the patients. Muscle samples were taken from the thigh. Glyceraldehyde-3-phosphate (triosephosphate) dehydrogenase (TPD), lactate dehydrogenase (LDH), citrate synthetase (CS) and cytochrome oxidase (cytox) activities were measured and the ultrastructure of the muscle specimens was studied by electron microscopy. Immobilization of the healthy persons induced decreased activities of CS, but those of TPD, LDH and cytox remained unaffected. Return to normal life restored the CS activity. The activities of the four enzymes were lower in the patients than in the healthy subjects after immobilization. During normal life, the activities slowly rose to levels as those seen in the healthy subjects. In connection with the acute disease, focal ultrastructural changes within the muscle were found. The changes were similar to those reported to occur in other, more specific muscle diseases.", "contents": "Effects of viral and mycoplasma infections on ultrastructure and enzyme activities in human skeletal muscle. The effect on skeletal muscle of acute viral and mycoplasma infections in thirteen men of ages ranging between 20-42 years has been studied. Comparisons are made with eight healthy men in the age group 22-29 years who were confined to bed for periods of time of lengths similar to the confinement to bed of the patients. Muscle samples were taken from the thigh. Glyceraldehyde-3-phosphate (triosephosphate) dehydrogenase (TPD), lactate dehydrogenase (LDH), citrate synthetase (CS) and cytochrome oxidase (cytox) activities were measured and the ultrastructure of the muscle specimens was studied by electron microscopy. Immobilization of the healthy persons induced decreased activities of CS, but those of TPD, LDH and cytox remained unaffected. Return to normal life restored the CS activity. The activities of the four enzymes were lower in the patients than in the healthy subjects after immobilization. During normal life, the activities slowly rose to levels as those seen in the healthy subjects. In connection with the acute disease, focal ultrastructural changes within the muscle were found. The changes were similar to those reported to occur in other, more specific muscle diseases."} {"id": "PMID:176869", "title": "Specificity of hormonal responsiveness in vitro. Effect of sex steroids on non-malignant rat cells compared with the effect on cells from rat tumours.", "content": "Since mammary tumours and sarcomas in the rat both have been shown to be sensitive to steroid hormone in vitro, a search for a non-steroid sensitive rat tissue was made. Neonatal cerebellar medulloblasts in the rat did not respond to high concentrations of steroids if cultured as organ culture. The relevance of this finding to the specificity of steroid response assays in vitro is discussed.", "contents": "Specificity of hormonal responsiveness in vitro. Effect of sex steroids on non-malignant rat cells compared with the effect on cells from rat tumours. Since mammary tumours and sarcomas in the rat both have been shown to be sensitive to steroid hormone in vitro, a search for a non-steroid sensitive rat tissue was made. Neonatal cerebellar medulloblasts in the rat did not respond to high concentrations of steroids if cultured as organ culture. The relevance of this finding to the specificity of steroid response assays in vitro is discussed."} {"id": "PMID:176870", "title": "Biosynthesis of unsaturated fatty acids in cultured minimal deviations hepatoma 7288 C cells.", "content": "Minimal Deviation Hepatoma 7288 C cells were cultured in confluent layer with labeled linoleic, alpha-linolenic, eicosa-8,11,14-trienoic and stearic acids. The cells in culture preserved their ability to convert stearic acid to oleic acid. They also synthesized arachidonic acid from linoleic acid or eicosa-8,11,14-trienoic acid. The conversion was very low with linoleic acid and high with eicosatrienoic acid. Eicosapentaenoic acid and other homologs of the alpha-linolenic acid family were synthesized from alpha-linolenic acid. The biosynthetic patterns were the cells was modified by the fatty acid composition of the media.", "contents": "Biosynthesis of unsaturated fatty acids in cultured minimal deviations hepatoma 7288 C cells. Minimal Deviation Hepatoma 7288 C cells were cultured in confluent layer with labeled linoleic, alpha-linolenic, eicosa-8,11,14-trienoic and stearic acids. The cells in culture preserved their ability to convert stearic acid to oleic acid. They also synthesized arachidonic acid from linoleic acid or eicosa-8,11,14-trienoic acid. The conversion was very low with linoleic acid and high with eicosatrienoic acid. Eicosapentaenoic acid and other homologs of the alpha-linolenic acid family were synthesized from alpha-linolenic acid. The biosynthetic patterns were the cells was modified by the fatty acid composition of the media."} {"id": "PMID:176871", "title": "Modification of synaptic efficiency, experiments in blatta orientalis.", "content": "The efficiency of synapt ic transmission in a nervous pathway--metathoracic ganglia from the cockroach--can be increased by various experimental situations, i.e., removal, immobilization or denervation of the forelegs of insects in ventral position. Leg immobilization with the insect in supine position by itself determines a minor increase which is not enhanced by removal or denervation of the forelegs. Under these conditions, the insects are able to hold their antennae with a midleg immediately after any of the leg treatments. On the other hand, if the insects are allowed to be in ventral position they can hold their antennae with a midleg only when they reach the ability to stand on the remaining three legs. During the time period needed to acquire this ability, the insects make repeated and spontaneous motor effects. The increase in synaptic efficiency observed and the achievement of the insect's ability to stand on three legs occur at about the same time. These observations suggest that the self-training determines the synaptic modifications which in turn could be related to the \"learnt\" behavioral reaction.", "contents": "Modification of synaptic efficiency, experiments in blatta orientalis. The efficiency of synapt ic transmission in a nervous pathway--metathoracic ganglia from the cockroach--can be increased by various experimental situations, i.e., removal, immobilization or denervation of the forelegs of insects in ventral position. Leg immobilization with the insect in supine position by itself determines a minor increase which is not enhanced by removal or denervation of the forelegs. Under these conditions, the insects are able to hold their antennae with a midleg immediately after any of the leg treatments. On the other hand, if the insects are allowed to be in ventral position they can hold their antennae with a midleg only when they reach the ability to stand on the remaining three legs. During the time period needed to acquire this ability, the insects make repeated and spontaneous motor effects. The increase in synaptic efficiency observed and the achievement of the insect's ability to stand on three legs occur at about the same time. These observations suggest that the self-training determines the synaptic modifications which in turn could be related to the \"learnt\" behavioral reaction."} {"id": "PMID:176872", "title": "Protein synthesis in adrenal mitochondrial and post-mitochondrial fractions of ACTH-treated rats.", "content": "Short and prolonged administration of ACTH was used to study the effects of the hormone on protein synthesis in two subcellular fractions obtained from rat adrenals incubated in the presence of a (14C)-labelled amino acid mixture. Acute treatment with ACTH produced an increased labelling of the proteins of the post-mitochondrial (POST-MIT) fraction only. On the other hand, treatment with ACTH for 4-28 days, significantly increased the specific activity of proteins in the mitochondrial (MIT) fraction, without change in the radiolabelling of the POST-MIT fraction. The incorporation of (14C)-labelled amino acids into the proteins of the MIT and POST-MIT fractions, from control or ACTH-treated adrenals, was reduced by inhibitors of cytoplasmic protein synthesis (puromycin and cycloheximide). This suggests that the increased labelling of the MIT fraction after prolonged ACTH might be related to a translocation of cytoplasmic proteins to the mitochondrion.", "contents": "Protein synthesis in adrenal mitochondrial and post-mitochondrial fractions of ACTH-treated rats. Short and prolonged administration of ACTH was used to study the effects of the hormone on protein synthesis in two subcellular fractions obtained from rat adrenals incubated in the presence of a (14C)-labelled amino acid mixture. Acute treatment with ACTH produced an increased labelling of the proteins of the post-mitochondrial (POST-MIT) fraction only. On the other hand, treatment with ACTH for 4-28 days, significantly increased the specific activity of proteins in the mitochondrial (MIT) fraction, without change in the radiolabelling of the POST-MIT fraction. The incorporation of (14C)-labelled amino acids into the proteins of the MIT and POST-MIT fractions, from control or ACTH-treated adrenals, was reduced by inhibitors of cytoplasmic protein synthesis (puromycin and cycloheximide). This suggests that the increased labelling of the MIT fraction after prolonged ACTH might be related to a translocation of cytoplasmic proteins to the mitochondrion."} {"id": "PMID:176873", "title": "Disturbances in voluntary recruitment order of low and high frequency motor units on blockades of proprioceptive afferent activity.", "content": "The voluntary recruitment order of anterior tibial motor units was studied in electromyographic recordings using both low and high impedance electrodes. It was shown in previous papers, that the recruitment order in sustained voluntary contraction is normally stable and that motor units with low thresholds discharge at low, regular frequencies and that motor units with high thresholds discharge at higher and more irregular frequencies. In this paper the consequences for the discharge properties of reduced afferent inflow in sustained voluntary contraction were studied, using partial ischemic or lidocain blockades of the muscle nerve and local cooling of the muscle belly. 1. The recruitment order of certain low and certain high frequency units was reversed. 2. The muscle tension and sense of effort necessary for tonic firing were increased for certain low frequency units but decreased for certain high frequency units. 3. On severe reduction of the afferent inflow, the differences in discharge pattern between low and high frequency units were decreased. It is concluded that the recruitment of low frequency units before high frequency units in sustained voluntary contraction is partly due to proprioceptive afferent activity favouring low frequency units and disfavouring high frequency units. It is also concluded that the afferent inflow is involved in restricting certain units to low frequency discharge and others to high frequency discharge.", "contents": "Disturbances in voluntary recruitment order of low and high frequency motor units on blockades of proprioceptive afferent activity. The voluntary recruitment order of anterior tibial motor units was studied in electromyographic recordings using both low and high impedance electrodes. It was shown in previous papers, that the recruitment order in sustained voluntary contraction is normally stable and that motor units with low thresholds discharge at low, regular frequencies and that motor units with high thresholds discharge at higher and more irregular frequencies. In this paper the consequences for the discharge properties of reduced afferent inflow in sustained voluntary contraction were studied, using partial ischemic or lidocain blockades of the muscle nerve and local cooling of the muscle belly. 1. The recruitment order of certain low and certain high frequency units was reversed. 2. The muscle tension and sense of effort necessary for tonic firing were increased for certain low frequency units but decreased for certain high frequency units. 3. On severe reduction of the afferent inflow, the differences in discharge pattern between low and high frequency units were decreased. It is concluded that the recruitment of low frequency units before high frequency units in sustained voluntary contraction is partly due to proprioceptive afferent activity favouring low frequency units and disfavouring high frequency units. It is also concluded that the afferent inflow is involved in restricting certain units to low frequency discharge and others to high frequency discharge."} {"id": "PMID:176874", "title": "Effects from the vestibulospinal tract on transmission from primary afferents to ventral spino-cerebellar tract neurones.", "content": "Convergence of vestibulospinal and segmental effects onto spinal interneurones which project to the ventral spino-cerebellar tract (VSCT) neurones has been studied by intracellular recording in VSCT cells. The disynaptic Ia IPSPs evoked in a group of VSCT neurones from the quadriceps nerve are monosynaptically facilitated by the vestibulospinal tract while there was no facilitation of Ia IPSP evoked from a flexor nerve. These results support the view that Ia inhibition to VSCT cells and motoneurones is mediated by common interneurones. The disynaptic inhibition evoked in other VSCT cells from the vestibulospinal tract is facilitated by volleys in the contralateral flexor reflex afferents (FRA) or bilaterally from the FRA. It is postulated that these actions are mediated by collaterals of the interneurones responsible for the analogous effects in motoneurones. Findings are reported suggesting that the monosynaptic vestibulospinal EPSP in VSCT cells in most cases is collateral to the excitatory input to the last order interneurones of reflex pathways from the FRA to motoneurones and only exceptionally to the corresponding input to Ia inhibitory interneurones. In many VSCT cells the vestibulospinal tract evoked disynaptic EPSPs which are facilitated from the FRA; the functional significance of this action is uncertain. The results are consistent with the hypothesis that VSCT neurones signal information on interneuronal transmission to motoneurones.", "contents": "Effects from the vestibulospinal tract on transmission from primary afferents to ventral spino-cerebellar tract neurones. Convergence of vestibulospinal and segmental effects onto spinal interneurones which project to the ventral spino-cerebellar tract (VSCT) neurones has been studied by intracellular recording in VSCT cells. The disynaptic Ia IPSPs evoked in a group of VSCT neurones from the quadriceps nerve are monosynaptically facilitated by the vestibulospinal tract while there was no facilitation of Ia IPSP evoked from a flexor nerve. These results support the view that Ia inhibition to VSCT cells and motoneurones is mediated by common interneurones. The disynaptic inhibition evoked in other VSCT cells from the vestibulospinal tract is facilitated by volleys in the contralateral flexor reflex afferents (FRA) or bilaterally from the FRA. It is postulated that these actions are mediated by collaterals of the interneurones responsible for the analogous effects in motoneurones. Findings are reported suggesting that the monosynaptic vestibulospinal EPSP in VSCT cells in most cases is collateral to the excitatory input to the last order interneurones of reflex pathways from the FRA to motoneurones and only exceptionally to the corresponding input to Ia inhibitory interneurones. In many VSCT cells the vestibulospinal tract evoked disynaptic EPSPs which are facilitated from the FRA; the functional significance of this action is uncertain. The results are consistent with the hypothesis that VSCT neurones signal information on interneuronal transmission to motoneurones."} {"id": "PMID:176875", "title": "Rubrospinal effects on ventral spinocerebellar tract neurones.", "content": "Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.", "contents": "Rubrospinal effects on ventral spinocerebellar tract neurones. Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms."} {"id": "PMID:176876", "title": "A comparative study of the effects of cholestyramine and neomycin in the treatment of type II hyperlipoproteinaemia.", "content": "A comparative study of the effects of cholestyramine and neomycin has been carried out in 35 patients with severe type II hyperlipoproteinaemia. Both agents were administered during a period of 18 weeks, the daily dosages being 12, 16 or 20 g cholestyramine and 1, 1.5 or 2 g neomycin. The mean decrease in cholesterol concentration was 22% with cholestyramine and 23% with neomycin. There was no difference in effect between the two agents and between the doses used. No significant influence on triglyceride concentration and on body weight was observed. No signs of deficiencies in fat-soluble vitamins were found. Anticoagulant requirements increased during cholestyramine medication. No signs of hyperchloraemic acidosis were observed during treatment with colestyramine. Cholestyramine was tolerated less well than neomycin: it had to be discontinued in 8 cases. Neomycin was not tolerated by 3 patients. The majority of the patients preferred neomycin.", "contents": "A comparative study of the effects of cholestyramine and neomycin in the treatment of type II hyperlipoproteinaemia. A comparative study of the effects of cholestyramine and neomycin has been carried out in 35 patients with severe type II hyperlipoproteinaemia. Both agents were administered during a period of 18 weeks, the daily dosages being 12, 16 or 20 g cholestyramine and 1, 1.5 or 2 g neomycin. The mean decrease in cholesterol concentration was 22% with cholestyramine and 23% with neomycin. There was no difference in effect between the two agents and between the doses used. No significant influence on triglyceride concentration and on body weight was observed. No signs of deficiencies in fat-soluble vitamins were found. Anticoagulant requirements increased during cholestyramine medication. No signs of hyperchloraemic acidosis were observed during treatment with colestyramine. Cholestyramine was tolerated less well than neomycin: it had to be discontinued in 8 cases. Neomycin was not tolerated by 3 patients. The majority of the patients preferred neomycin."} {"id": "PMID:176880", "title": "Phosphopyridoxal complexes with histamine and histidine. (4) The kinetics of complex formation between histidine and pyridoxal 5' -phosphate in the presence of bacterial histidine decarboxylase.", "content": "The dynamics of the complex formation between pyridoxal 5'-phosphate (PLP) and histidine in the presence of bacterial histidine decarboxylase was examined. Since PLP is able to form a cyclic product with histidine and histamine, the possibility of complex formation between PLP and histamine formed during a decarboxylation reaction was examined too. It was found that the cyclization reaction between PLP and histidine is equimolecular and the rate of cyclic product formation is not significantly influenced by the presence of enzyme. In the presence of bacterial histidine decarboxylase both the cyclization reaction and cyclic product formation were observed. Predominance of histamine or cyclic product formation was dependent on pH and substrate concentration. In the presence of histidine and enzymatic protein, histamine formed during the decarboxylation reaction was unable to form a cyclic product with PLP.", "contents": "Phosphopyridoxal complexes with histamine and histidine. (4) The kinetics of complex formation between histidine and pyridoxal 5' -phosphate in the presence of bacterial histidine decarboxylase. The dynamics of the complex formation between pyridoxal 5'-phosphate (PLP) and histidine in the presence of bacterial histidine decarboxylase was examined. Since PLP is able to form a cyclic product with histidine and histamine, the possibility of complex formation between PLP and histamine formed during a decarboxylation reaction was examined too. It was found that the cyclization reaction between PLP and histidine is equimolecular and the rate of cyclic product formation is not significantly influenced by the presence of enzyme. In the presence of bacterial histidine decarboxylase both the cyclization reaction and cyclic product formation were observed. Predominance of histamine or cyclic product formation was dependent on pH and substrate concentration. In the presence of histidine and enzymatic protein, histamine formed during the decarboxylation reaction was unable to form a cyclic product with PLP."} {"id": "PMID:176881", "title": "Metabolic investigations after xylitol infusion in human subjects.", "content": "Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed.", "contents": "Metabolic investigations after xylitol infusion in human subjects. Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed."} {"id": "PMID:176883", "title": "Light and electron microscopic features of a pituitary adenoma in Nelson's syndrome.", "content": "Electron microscopy of an amphophil pituitary adenoma surgically removed from a 51-year-old woman who had Nelson's syndrome revealed that the tumor was composed of melanocorticotroph cells. This finding is consistent with the view that in the human pituitary gland one single cell type produces both adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH). In contrast to the ultrastructure of pituitary adenomas associated with Cushing's syndrome, no or only very few microfilaments were detected in the cytoplasm of the tumor cells, suggesting that adrenocortical steroids are required for the formation of microfilaments. The presence or absence of microfilaments in the tumor cells may be regarded as a distinguishing ultrastructural feature between Cushing's syndrome and Nelson's syndrome. It appears that changes in the level of circulating corticoids may affect the ultrastructural features of melanocorticotroph cells not only in normal pituitaries but also in adenohypophyseal adenomas.", "contents": "Light and electron microscopic features of a pituitary adenoma in Nelson's syndrome. Electron microscopy of an amphophil pituitary adenoma surgically removed from a 51-year-old woman who had Nelson's syndrome revealed that the tumor was composed of melanocorticotroph cells. This finding is consistent with the view that in the human pituitary gland one single cell type produces both adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH). In contrast to the ultrastructure of pituitary adenomas associated with Cushing's syndrome, no or only very few microfilaments were detected in the cytoplasm of the tumor cells, suggesting that adrenocortical steroids are required for the formation of microfilaments. The presence or absence of microfilaments in the tumor cells may be regarded as a distinguishing ultrastructural feature between Cushing's syndrome and Nelson's syndrome. It appears that changes in the level of circulating corticoids may affect the ultrastructural features of melanocorticotroph cells not only in normal pituitaries but also in adenohypophyseal adenomas."} {"id": "PMID:176884", "title": "Steroid-binding proteins in carcinoma of the human male breast.", "content": "Receptor sites for a group of four steroid hormones were estimated by competitive binding assay of a biopsy specimen of carcinoma from a male breast. The results indicate that the tissue contained a significant number of binding sites for 17beta estradiol, and probably for dihydrotestosterone and progesterone, but not for testosterone. These preliminary data suggest that, as in the female, certain mammary carcinomas in the male may be under the influence of steroid hormones. Correlation of such data with responses to therapy may help to establish a more rational approach to the treatment of carcinoma of the male breast.", "contents": "Steroid-binding proteins in carcinoma of the human male breast. Receptor sites for a group of four steroid hormones were estimated by competitive binding assay of a biopsy specimen of carcinoma from a male breast. The results indicate that the tissue contained a significant number of binding sites for 17beta estradiol, and probably for dihydrotestosterone and progesterone, but not for testosterone. These preliminary data suggest that, as in the female, certain mammary carcinomas in the male may be under the influence of steroid hormones. Correlation of such data with responses to therapy may help to establish a more rational approach to the treatment of carcinoma of the male breast."} {"id": "PMID:176885", "title": "Positive mono-spot test in histiocytic medullary reticulosis.", "content": "A case of rapidly fatal histiocytic medullary reticulosis in which two positive mono-spot tests were found is presented. In addition, there was a low liter antibody to EB virus. The patient died with a bleeding diathesis terminally. Postmortem examinations confirmed the diagnosis of histiocytic medullary reticulosis.", "contents": "Positive mono-spot test in histiocytic medullary reticulosis. A case of rapidly fatal histiocytic medullary reticulosis in which two positive mono-spot tests were found is presented. In addition, there was a low liter antibody to EB virus. The patient died with a bleeding diathesis terminally. Postmortem examinations confirmed the diagnosis of histiocytic medullary reticulosis."} {"id": "PMID:176886", "title": "Isolation of mycobacteria from clinical specimens by use of selective 7H11 medium.", "content": "7H11 agar containing carbenicillin, amphotericin B, polymyxin B and trimethoprim lactate (selective 7H11 or S7H11) was used for the selective isolation of mycobacteria from clinical specimens. This medium as previously described contained 100 mug. carbenicillin per ml. It was found that reducing the concentration of carbenicillin to 50 mug. per ml. made S7H11 less inhibitory to certain strains of mycobacteria. However, some strains of M. kansaii, M. intracellulare, and M. gordonae still do not grow well on S7H11. Of 3,134 clinical specimens (mostly sputum) received, processed, and plated on 7H11 agar and the S7H11 medium, 508 positive specimens were isolated. Of these, 402 were positive on both types of media, 30 were positive on 7H11 only, 19 were positive on S7H11 only, 52 were contaminated on 7H11 but positive on S7H11, while only 5 were contaminated on S7H11 and positive on the plain medium. Thus, the total positive specimens on 7H11 was 437 and total positive specimens on the selective medium was 473. Used in conjunction with nonselective media, S7H11 agar appears to be a valuable culture medium for used in diagnostic mycobacteriology laboratories.", "contents": "Isolation of mycobacteria from clinical specimens by use of selective 7H11 medium. 7H11 agar containing carbenicillin, amphotericin B, polymyxin B and trimethoprim lactate (selective 7H11 or S7H11) was used for the selective isolation of mycobacteria from clinical specimens. This medium as previously described contained 100 mug. carbenicillin per ml. It was found that reducing the concentration of carbenicillin to 50 mug. per ml. made S7H11 less inhibitory to certain strains of mycobacteria. However, some strains of M. kansaii, M. intracellulare, and M. gordonae still do not grow well on S7H11. Of 3,134 clinical specimens (mostly sputum) received, processed, and plated on 7H11 agar and the S7H11 medium, 508 positive specimens were isolated. Of these, 402 were positive on both types of media, 30 were positive on 7H11 only, 19 were positive on S7H11 only, 52 were contaminated on 7H11 but positive on S7H11, while only 5 were contaminated on S7H11 and positive on the plain medium. Thus, the total positive specimens on 7H11 was 437 and total positive specimens on the selective medium was 473. Used in conjunction with nonselective media, S7H11 agar appears to be a valuable culture medium for used in diagnostic mycobacteriology laboratories."} {"id": "PMID:176887", "title": "Is a rhinovirus vaccine possible?", "content": "Renewal of support for efforts to develop a rhinovirus vaccine seems justified in the light of newer epidemiologic and immunologic studies. The major contribution of RV to acute upper respiratory disease in all age groups but especially in young children emphasizes the public health importance of an effective vaccine. Epidemiologic surveillance of RV infections in widely separated areas has identified two relevant phenomena. First, in each area, certain serotypes were more frequently encountered and tended to persist. Such \"common\" serotypes accounted for a disproportionate share of the infections recognized and, hence, constitute special targets for immunization. Second, a clear increase over time in the proportion of RV isolates representing higher numbered (types 56-89) serotypes or untypable strains (potentially new serotypes) suggests that new serotypes continue to emerge as the result of progressive antigenic shift. The common origin of the multitudinous RV serotypes so suggested is consistent with the extensive antigenic cross-relations which are becoming evident. Systematic cross-testing with monospecific antisera, especially when high titer sera are employed, has revealed an appreciable number of one-way and reciprocal relations. Largely fortuitous observations of naturally or experimentally infected humans have revealed many additional cross-relations manifested by concurrent response to heterologous RV and presumably attributable to sensitizations resulting from prior RV infections. A model for this has been provided by rabbits immunized sequentially with different potent RV immunogens. Available information as displayed in figure 2 indicates that extensive cross-relations do exist and that sizeable groups of closely related serotypes may be identified. More intensive search for heterotypic response to infection of man coupled with selective use of the rabbit model should define the full extent and strength of cross-relations and identify completely the more closely related groups of serotypes as the basis for formulation of a broadly effective RV vaccine containing a limited number of serotypes. The cross-relations described are based entirely on development of serum neutralizing antibody, the presence of which in man is clearly correlated with relative protection against infection and disease. While this protection may well prove to be mediated largely by concomitant nasal secretory antibody, it is not unreasonable to expect that the antigenic cross-relations also would be manifested in secretory antibody response. These important questions concerning secretory antibody can be best explored in a limited series of volunteer trials with selected cross-related RV serotypes in which homotypic and heterotypic protection could be correlated with serum and nasal secretory antibody. The state of current knowledge, as I view it, is sufficient to justify initiation of such trials at any time.", "contents": "Is a rhinovirus vaccine possible? Renewal of support for efforts to develop a rhinovirus vaccine seems justified in the light of newer epidemiologic and immunologic studies. The major contribution of RV to acute upper respiratory disease in all age groups but especially in young children emphasizes the public health importance of an effective vaccine. Epidemiologic surveillance of RV infections in widely separated areas has identified two relevant phenomena. First, in each area, certain serotypes were more frequently encountered and tended to persist. Such \"common\" serotypes accounted for a disproportionate share of the infections recognized and, hence, constitute special targets for immunization. Second, a clear increase over time in the proportion of RV isolates representing higher numbered (types 56-89) serotypes or untypable strains (potentially new serotypes) suggests that new serotypes continue to emerge as the result of progressive antigenic shift. The common origin of the multitudinous RV serotypes so suggested is consistent with the extensive antigenic cross-relations which are becoming evident. Systematic cross-testing with monospecific antisera, especially when high titer sera are employed, has revealed an appreciable number of one-way and reciprocal relations. Largely fortuitous observations of naturally or experimentally infected humans have revealed many additional cross-relations manifested by concurrent response to heterologous RV and presumably attributable to sensitizations resulting from prior RV infections. A model for this has been provided by rabbits immunized sequentially with different potent RV immunogens. Available information as displayed in figure 2 indicates that extensive cross-relations do exist and that sizeable groups of closely related serotypes may be identified. More intensive search for heterotypic response to infection of man coupled with selective use of the rabbit model should define the full extent and strength of cross-relations and identify completely the more closely related groups of serotypes as the basis for formulation of a broadly effective RV vaccine containing a limited number of serotypes. The cross-relations described are based entirely on development of serum neutralizing antibody, the presence of which in man is clearly correlated with relative protection against infection and disease. While this protection may well prove to be mediated largely by concomitant nasal secretory antibody, it is not unreasonable to expect that the antigenic cross-relations also would be manifested in secretory antibody response. These important questions concerning secretory antibody can be best explored in a limited series of volunteer trials with selected cross-related RV serotypes in which homotypic and heterotypic protection could be correlated with serum and nasal secretory antibody. The state of current knowledge, as I view it, is sufficient to justify initiation of such trials at any time."} {"id": "PMID:176889", "title": "Neurohormonal control of gonadotropic secretion in primates.", "content": "With immunohistochemical techniques, products from both the parvicellular system (such as Gn-RH) and from the magnocellular system (vasopressin, oxytocin, and neurophysins) have been shown to be present in the neurons ending around the hypothalamopituitary portal capillary system. A neurosurgical technique for prolonged collection of pituitary stalk blood has been developed. Gn-RH, vasopressin, and neurophysins have been found in large amounts in pituitary stalk blood. Gn-RH levels were found to vary in a pulsatile fashion, thereby providing direct evidence for hypothalamic modulation of the discharge of LH by the pituitary. The finding of large amounts of estrogen-neurophysin in portal vein blood adds further evidence to the hypothesis that \"estrogen\" neurophysin may play a role in the control by the hypothalamus over the secretion of gonadotropins.", "contents": "Neurohormonal control of gonadotropic secretion in primates. With immunohistochemical techniques, products from both the parvicellular system (such as Gn-RH) and from the magnocellular system (vasopressin, oxytocin, and neurophysins) have been shown to be present in the neurons ending around the hypothalamopituitary portal capillary system. A neurosurgical technique for prolonged collection of pituitary stalk blood has been developed. Gn-RH, vasopressin, and neurophysins have been found in large amounts in pituitary stalk blood. Gn-RH levels were found to vary in a pulsatile fashion, thereby providing direct evidence for hypothalamic modulation of the discharge of LH by the pituitary. The finding of large amounts of estrogen-neurophysin in portal vein blood adds further evidence to the hypothesis that \"estrogen\" neurophysin may play a role in the control by the hypothalamus over the secretion of gonadotropins."} {"id": "PMID:176888", "title": "Case report. Clostridium perfringens septicemia with detection of phospholipase C activity in the serum.", "content": "Clostridium perfringens septicemia with massive hemolysis is described in an elderly woman with refractory anemia. This case is highly unusual in that (1) the diagnosis was made during life by discovery of the organisms on a routine peripheral blood film, and that (2) phospholipase C activity was detected in the serum.", "contents": "Case report. Clostridium perfringens septicemia with detection of phospholipase C activity in the serum. Clostridium perfringens septicemia with massive hemolysis is described in an elderly woman with refractory anemia. This case is highly unusual in that (1) the diagnosis was made during life by discovery of the organisms on a routine peripheral blood film, and that (2) phospholipase C activity was detected in the serum."} {"id": "PMID:176891", "title": "Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton.", "content": "A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa). Heterozygotes (Tsk/+) have tight skins with marked hyperplasia of the subcutaneous loose connective tissues, increased growth of cartilage and bone, and small tendons with hyperplasia of the tendon sheaths. In the loose connective tissue there are large accumulations of microfibrils in the intercellular space. In spite of the increased skeletal size, body weight is not increased. Increase in size of the thoracic skeleton is especially pronounced and leads to pathologic distentsion of the hollow thoracic viscera. Concentration of growth hormone in the pituitary and plasma is normal. Homozygotes (Tsk/TSK) die in utero at 7 to 8 days of gestation. We propose the hypothesis that Tsk might act by causing defective cell receptors with high affinity for a somatomedin-like factor promoting growth of cartilage, bone, and connective tissue and low affinity for a multiplication-stimulating factor promoting embryonic growth.", "contents": "Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton. A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa). Heterozygotes (Tsk/+) have tight skins with marked hyperplasia of the subcutaneous loose connective tissues, increased growth of cartilage and bone, and small tendons with hyperplasia of the tendon sheaths. In the loose connective tissue there are large accumulations of microfibrils in the intercellular space. In spite of the increased skeletal size, body weight is not increased. Increase in size of the thoracic skeleton is especially pronounced and leads to pathologic distentsion of the hollow thoracic viscera. Concentration of growth hormone in the pituitary and plasma is normal. Homozygotes (Tsk/TSK) die in utero at 7 to 8 days of gestation. We propose the hypothesis that Tsk might act by causing defective cell receptors with high affinity for a somatomedin-like factor promoting growth of cartilage, bone, and connective tissue and low affinity for a multiplication-stimulating factor promoting embryonic growth."} {"id": "PMID:176892", "title": "Ca-activated ATPase activity in subcellular fractions of mouse pancreatic islets.", "content": "Ca-stimulated ATPase activity has been demonstrated in homogenates of mouse pancreatic islets. On subcellular fractionation Ca-ATPase activity was found in secretory granules, mitochondria, and microsomes, but not in the postmicrosomal fractions. Highest specific activity was found in the granules. In all active subcellular fractions two Km(Ca) values for Ca-ATPase around 7.0 X 10(-6) and 1.8 X 10(-7) M were estimated. Assuming an ATP hydrolysis:Ca pumping ratio of 1:2, the highest capacity for active Ca transport was found in secretory granules and mitochondria. Concentrations of 40 mM or higher of Na and 10(-5) M cyclic AMP inhibited Ca-ATPase in all subfractions. Caffeine at a concentration of 10 mM inhibited Ca-ATPase significantly in secretory granules and microsomes. Also MG-ATPase activity was demonstrated in the various subfractions. This activity was compared with that of Ca-ATPase at identical concentrations of free metal ions and in the absence or presence of various inhibitors. It was concluded that high-affinity Ca-ATPase and Mg-ATPase are two different enzymic entities. Ca-ATPase may tentatively be assumed to participate in active transport of Ca between intracellular compartments and to constitute a Ca-accumulating system which returns the cytosolic free Ca concentration to the resting state after stimulation of the beta-cells by secretagogues. This enzyme may therefore play a significant role in regulation of insulin release.", "contents": "Ca-activated ATPase activity in subcellular fractions of mouse pancreatic islets. Ca-stimulated ATPase activity has been demonstrated in homogenates of mouse pancreatic islets. On subcellular fractionation Ca-ATPase activity was found in secretory granules, mitochondria, and microsomes, but not in the postmicrosomal fractions. Highest specific activity was found in the granules. In all active subcellular fractions two Km(Ca) values for Ca-ATPase around 7.0 X 10(-6) and 1.8 X 10(-7) M were estimated. Assuming an ATP hydrolysis:Ca pumping ratio of 1:2, the highest capacity for active Ca transport was found in secretory granules and mitochondria. Concentrations of 40 mM or higher of Na and 10(-5) M cyclic AMP inhibited Ca-ATPase in all subfractions. Caffeine at a concentration of 10 mM inhibited Ca-ATPase significantly in secretory granules and microsomes. Also MG-ATPase activity was demonstrated in the various subfractions. This activity was compared with that of Ca-ATPase at identical concentrations of free metal ions and in the absence or presence of various inhibitors. It was concluded that high-affinity Ca-ATPase and Mg-ATPase are two different enzymic entities. Ca-ATPase may tentatively be assumed to participate in active transport of Ca between intracellular compartments and to constitute a Ca-accumulating system which returns the cytosolic free Ca concentration to the resting state after stimulation of the beta-cells by secretagogues. This enzyme may therefore play a significant role in regulation of insulin release."} {"id": "PMID:176893", "title": "The pathogenesis of vesicular stomatitis virus, serotype Indiana, in Aedes aegypti mosquitoes. I. Intrathoracic injection.", "content": "Analysis of infectious virus particles after intrathoracic injection revealed that Aedes aegypti mosquito tissues are capable of supporting the growth of vesicular stomatitis virus (VSV), serotype Indiana. Although all tissues assayed (salivary gland, midgut, diverticulum, malphigian tubules, and ovary) were capable of supporting VSV growth, the salivary gland was the only organ capable of maintaining an appreciable amount of virus for periods longer than 9 days postinfection. Electron microscopic studies of infected tissues showed virus particles consistently within the cell cytoplasm of all organs with no evidence of nuclear involvement. Direct evidence of crystalline formation of VSV in the apical cavities of salivary gland tissue was demonstrated.", "contents": "The pathogenesis of vesicular stomatitis virus, serotype Indiana, in Aedes aegypti mosquitoes. I. Intrathoracic injection. Analysis of infectious virus particles after intrathoracic injection revealed that Aedes aegypti mosquito tissues are capable of supporting the growth of vesicular stomatitis virus (VSV), serotype Indiana. Although all tissues assayed (salivary gland, midgut, diverticulum, malphigian tubules, and ovary) were capable of supporting VSV growth, the salivary gland was the only organ capable of maintaining an appreciable amount of virus for periods longer than 9 days postinfection. Electron microscopic studies of infected tissues showed virus particles consistently within the cell cytoplasm of all organs with no evidence of nuclear involvement. Direct evidence of crystalline formation of VSV in the apical cavities of salivary gland tissue was demonstrated."} {"id": "PMID:176894", "title": "Operative cholangiography in uncomplicated biliary tract surgery. Review of 354 cholangiography studies in patients without indication of common duct pathology.", "content": "The literature of the past ten years is replete with articles on \"routine* cholangiography, with particular reference to the overlooked or \"unsuspected\" stone. Many series do not differentiate between T-tube cholangiograms performed after common duct exploration and those performed on patients with and without the usual clinical or operative indications for common duct exploration. We present a pure operative cholangiographic study of 354 patients with apparent uncomplicated bilary tract disease; a significant incidence of unsuspected pathologic features are demonstrated. Can a convenient and innocuous procedure like routine operative cholangiography continue to be ignored, even in the most routine of cases?", "contents": "Operative cholangiography in uncomplicated biliary tract surgery. Review of 354 cholangiography studies in patients without indication of common duct pathology. The literature of the past ten years is replete with articles on \"routine* cholangiography, with particular reference to the overlooked or \"unsuspected\" stone. Many series do not differentiate between T-tube cholangiograms performed after common duct exploration and those performed on patients with and without the usual clinical or operative indications for common duct exploration. We present a pure operative cholangiographic study of 354 patients with apparent uncomplicated bilary tract disease; a significant incidence of unsuspected pathologic features are demonstrated. Can a convenient and innocuous procedure like routine operative cholangiography continue to be ignored, even in the most routine of cases?"} {"id": "PMID:176895", "title": "Selective hepatic venography in primary liver cell carcinoma.", "content": "With apparent inoperable hepatic cell carcinoma, knowledge of adequate venous outflow from tumor-free liver tissue permits extensive resection with long survival.", "contents": "Selective hepatic venography in primary liver cell carcinoma. With apparent inoperable hepatic cell carcinoma, knowledge of adequate venous outflow from tumor-free liver tissue permits extensive resection with long survival."} {"id": "PMID:176896", "title": "The value of arteriography in the diagnosis and treatment of insulinomas.", "content": "Six arteriograms were performed in five patients with insulinoma. The method showed with precision the size and location of the tumor in five instances, whereas in one instance the method was unsuccessful. Arteriography was performed again with more refinements in technic, but was adequate in locating only the largest tumor. Since diagnostic accuracy of arteriography depends on the size of the tumor, and nonpalpable tumors are only occasionally located, the main problems in surgical treatment of insulinomas are unresolved.", "contents": "The value of arteriography in the diagnosis and treatment of insulinomas. Six arteriograms were performed in five patients with insulinoma. The method showed with precision the size and location of the tumor in five instances, whereas in one instance the method was unsuccessful. Arteriography was performed again with more refinements in technic, but was adequate in locating only the largest tumor. Since diagnostic accuracy of arteriography depends on the size of the tumor, and nonpalpable tumors are only occasionally located, the main problems in surgical treatment of insulinomas are unresolved."} {"id": "PMID:176897", "title": "Pancreatic tumor of mesenchymal origin presenting as obstructive jaundice.", "content": "A case of an unusual tumor occurring in the head of the pancreas is presented. Definitive diagnosis could not be made, the lesion being either a low grade myxofibrosarcoma or a benign fibrous histiocytoma. The literature is discussed and several cases believed to be pancreatic sarcomata are presented, only one of which was definitely of pancreatic origin. No other case of fibrous histiocytoma of the pancreas has been reported.", "contents": "Pancreatic tumor of mesenchymal origin presenting as obstructive jaundice. A case of an unusual tumor occurring in the head of the pancreas is presented. Definitive diagnosis could not be made, the lesion being either a low grade myxofibrosarcoma or a benign fibrous histiocytoma. The literature is discussed and several cases believed to be pancreatic sarcomata are presented, only one of which was definitely of pancreatic origin. No other case of fibrous histiocytoma of the pancreas has been reported."} {"id": "PMID:176903", "title": "A quantitative electron microscopic study of atypical structures in normal human cerebral cortex.", "content": "Biopsy samples of the cerebral cortex from four normal human brains were examined in the electron microscope for the presence of abnormalities related to neurones and neuroglia. Atypical forms of axons, axon terminals and dendrites, many of them similar to those described in a variety of pathological and experimental material, were found to occur in small but appreciable numbers. Neuroglia exhibiting atypical inclusions occurred but were much less common. Physiologically altered neuronal perikarya were not encountered apart from one neuronal death. An area of 3.6 x 10(5) mu2 was scanned from each brain and atypical structures were categorised and counted. The possible implications of the presence of these structures in normal brain in discussed and the need for neuropathologists and neuroanatomists to be aware of the existence of atypical forms of neuronal processes in normal human and animal brains is emphasised.", "contents": "A quantitative electron microscopic study of atypical structures in normal human cerebral cortex. Biopsy samples of the cerebral cortex from four normal human brains were examined in the electron microscope for the presence of abnormalities related to neurones and neuroglia. Atypical forms of axons, axon terminals and dendrites, many of them similar to those described in a variety of pathological and experimental material, were found to occur in small but appreciable numbers. Neuroglia exhibiting atypical inclusions occurred but were much less common. Physiologically altered neuronal perikarya were not encountered apart from one neuronal death. An area of 3.6 x 10(5) mu2 was scanned from each brain and atypical structures were categorised and counted. The possible implications of the presence of these structures in normal brain in discussed and the need for neuropathologists and neuroanatomists to be aware of the existence of atypical forms of neuronal processes in normal human and animal brains is emphasised."} {"id": "PMID:176906", "title": "Pathogenicity of an attenuated strain of transmissible gastroenteritis virus for newborn pigs.", "content": "The pathogenicity of a cell culture-attenuated strain of transmissible gastroenteritis virus for newborn pigs was investigated. Newborn (1- to 2-day-old) pigs were orally given 2 x 10(6) plaque-forming units of attenuated virus. All pigs developed mild diarrhea, but deaths did not occur. As determined by immunofluorescence and villous atropy, infection of the small intestine was limited to the caudal 50 to 66%. Fluorescing cells and atrophic villi were seen from 2 to 3 days until 6 to 7 days after exposure. Attenuated virus-exposed pigs produced circulating virus-neutralizing antibodies detectable as early as 5 days after exposure. By contrast, all pigs orally given 1 x 10(2) pig infective doses of virulent transmissible gastroenteritis virus developed severe diarrhea, and almost all of those not killed died within 2 to 5 days after exposure. In the latter pigs, the entire length of the small intestine, except for the first 4 to 5 cm, was infected with virus by 24 to 36 hours after exposure.", "contents": "Pathogenicity of an attenuated strain of transmissible gastroenteritis virus for newborn pigs. The pathogenicity of a cell culture-attenuated strain of transmissible gastroenteritis virus for newborn pigs was investigated. Newborn (1- to 2-day-old) pigs were orally given 2 x 10(6) plaque-forming units of attenuated virus. All pigs developed mild diarrhea, but deaths did not occur. As determined by immunofluorescence and villous atropy, infection of the small intestine was limited to the caudal 50 to 66%. Fluorescing cells and atrophic villi were seen from 2 to 3 days until 6 to 7 days after exposure. Attenuated virus-exposed pigs produced circulating virus-neutralizing antibodies detectable as early as 5 days after exposure. By contrast, all pigs orally given 1 x 10(2) pig infective doses of virulent transmissible gastroenteritis virus developed severe diarrhea, and almost all of those not killed died within 2 to 5 days after exposure. In the latter pigs, the entire length of the small intestine, except for the first 4 to 5 cm, was infected with virus by 24 to 36 hours after exposure."} {"id": "PMID:176907", "title": "Effects of crude extracts of various plants on infectious bovine rhinotracheitis virus-plaque production.", "content": "Extracts of 28 plants were tested without demonstable antiviral activity in an agar-overlay plaque-reduction antiviral assay system, using infectious bovine rhinotracheitis virus and bovine endocardial cell cultures. Ethanolic extract of Narcissus tazetta L bulb elicited antiviral activity by inhibition of viral plaque formation. Antiviral activity was demonstrated against infectious bovine rhinotracheitis and equine rhinopneumonitis viruses. Narcissus tazetta L bulb did not directly inactivate the virus extracellularly. The extract exhibited only limited toxicity to rapidly multiplying bovine endocardial cells at plaque-inhibitory levels and was not cytoxic to preformed confluent cell monolayers. Narcissus extract did not induce the formation of drug-resistant viral strains.", "contents": "Effects of crude extracts of various plants on infectious bovine rhinotracheitis virus-plaque production. Extracts of 28 plants were tested without demonstable antiviral activity in an agar-overlay plaque-reduction antiviral assay system, using infectious bovine rhinotracheitis virus and bovine endocardial cell cultures. Ethanolic extract of Narcissus tazetta L bulb elicited antiviral activity by inhibition of viral plaque formation. Antiviral activity was demonstrated against infectious bovine rhinotracheitis and equine rhinopneumonitis viruses. Narcissus tazetta L bulb did not directly inactivate the virus extracellularly. The extract exhibited only limited toxicity to rapidly multiplying bovine endocardial cells at plaque-inhibitory levels and was not cytoxic to preformed confluent cell monolayers. Narcissus extract did not induce the formation of drug-resistant viral strains."} {"id": "PMID:176908", "title": "Effects of vaccination infectious bovine rhinotracheitis and simultaneous administration of levamisole on primary humoral responses in calves.", "content": "In a study on the primary humoral response of calves vaccinated against infectious bovine rhinotracheitis (IBR) and simultaneously given levamisole, mild but consistent suppression of the group's geometric mean serum-neutralization titer to IBR virus occurred between 12 and 59 days later. The quantitative determination of circulating immunoglobulins (Ig) over the same period indicated a slight decrease in the IgG concentrations from an initial geometric mean concentration of 18.28 mg/ml before calves were vaccinated to 15.29 mg/ml after vaccination, and the control calves (vaccinated and given saline solution only) maintained their prevaccination IgG geometric mean concentration of 20.92 mg/ml. Difference was not observed in the circulating IgM values of the 2 groups. Levamisole had no apparent effect on the circulating Ig-bearing lymphocyte values when compared with control calves during the 24 hours of treatment. It was concluded that a single treatment of levamisole may mildly suppress the primary humoral response to IBR vaccination in calves, but it is unlikely that this would affect the animal's capability to recover from, or maintain resistance to, IBR infection.", "contents": "Effects of vaccination infectious bovine rhinotracheitis and simultaneous administration of levamisole on primary humoral responses in calves. In a study on the primary humoral response of calves vaccinated against infectious bovine rhinotracheitis (IBR) and simultaneously given levamisole, mild but consistent suppression of the group's geometric mean serum-neutralization titer to IBR virus occurred between 12 and 59 days later. The quantitative determination of circulating immunoglobulins (Ig) over the same period indicated a slight decrease in the IgG concentrations from an initial geometric mean concentration of 18.28 mg/ml before calves were vaccinated to 15.29 mg/ml after vaccination, and the control calves (vaccinated and given saline solution only) maintained their prevaccination IgG geometric mean concentration of 20.92 mg/ml. Difference was not observed in the circulating IgM values of the 2 groups. Levamisole had no apparent effect on the circulating Ig-bearing lymphocyte values when compared with control calves during the 24 hours of treatment. It was concluded that a single treatment of levamisole may mildly suppress the primary humoral response to IBR vaccination in calves, but it is unlikely that this would affect the animal's capability to recover from, or maintain resistance to, IBR infection."} {"id": "PMID:176904", "title": "The interaction between d-tubocurarine, pancuronium, polymyxin B, and neostigmine on neuromuscular function.", "content": "The interaction between pancuronium, d-tubocurarine, polymyxin B, and neostigmine was studied in the rat diaphragm-phrenic nerve preparation. Polymyxin B (5 mug/ml) did not affect twitch tension alone but decreased the pancuronium ED50 from 0.8 mug/ml to 0.32 mug/ml and the d-tubocurarine ED50 from 0.25 mug/ml to 0.15 mug/ml. Neostigmine (0.2 to 10 mug/ml) antagonized pancuronium or d-tubocurarine-induced depression of twitch tension. In contrast, neostigmine (0.001 to 0.2 mug/ml) augmented polymyxin B depression. Similarly, neostigmine (0.1 mug/ml) augmented combined polymyxin B-pancuronium or polymyxin B-d-tubocurarine depression of twitch tension. The authors conclude that polymyxin B potentiates the neuromuscular blockade from pancuronium or d-tubocurarine and that neostigmine further augments this block.", "contents": "The interaction between d-tubocurarine, pancuronium, polymyxin B, and neostigmine on neuromuscular function. The interaction between pancuronium, d-tubocurarine, polymyxin B, and neostigmine was studied in the rat diaphragm-phrenic nerve preparation. Polymyxin B (5 mug/ml) did not affect twitch tension alone but decreased the pancuronium ED50 from 0.8 mug/ml to 0.32 mug/ml and the d-tubocurarine ED50 from 0.25 mug/ml to 0.15 mug/ml. Neostigmine (0.2 to 10 mug/ml) antagonized pancuronium or d-tubocurarine-induced depression of twitch tension. In contrast, neostigmine (0.001 to 0.2 mug/ml) augmented polymyxin B depression. Similarly, neostigmine (0.1 mug/ml) augmented combined polymyxin B-pancuronium or polymyxin B-d-tubocurarine depression of twitch tension. The authors conclude that polymyxin B potentiates the neuromuscular blockade from pancuronium or d-tubocurarine and that neostigmine further augments this block."} {"id": "PMID:176910", "title": "Treating perforated jejunal ulcer, a complication in the Zollinger-Ellison syndrome.", "content": "What is considered to represent the fourth case of perforated jejunal ulcer in association with the Zollinger-Ellison syndrome reported in the literature is discussed. Although documented in the original paper by Zollinger and Ellison, this remains a notably rare complication. Generalized peritonitis and related pathophysiological phenomena make initial definitive correction of the ulcer diathesis an extremely riskly undertaking and ill-advised. We submit that primary ulcer resection followed by total gastrectomy when the patient becomes a more suitable operative risk is the preferred method of management. The literature would appear to support this clinical view.", "contents": "Treating perforated jejunal ulcer, a complication in the Zollinger-Ellison syndrome. What is considered to represent the fourth case of perforated jejunal ulcer in association with the Zollinger-Ellison syndrome reported in the literature is discussed. Although documented in the original paper by Zollinger and Ellison, this remains a notably rare complication. Generalized peritonitis and related pathophysiological phenomena make initial definitive correction of the ulcer diathesis an extremely riskly undertaking and ill-advised. We submit that primary ulcer resection followed by total gastrectomy when the patient becomes a more suitable operative risk is the preferred method of management. The literature would appear to support this clinical view."} {"id": "PMID:176911", "title": "Infiltrating ductal carcinoma of the breast in the postpubertal adolescent: a case report.", "content": "Infiltrating ductal carcinoma is an extremely rare neoplasm in the teenage or pre-teenage child. Routine pediatric physical examination should include careful examination of the breast and all palpable masses should be excised. Carcinoma occurring in the prepubertal child carries an improved prognosis particularly if the tumor stains PAS-positive. Carcinoma occurring in the postpubertal teenager probably carries the same prognosis as that in the adult and should be treated in a similar manner. The authors discuss such a case occurring in a 13-year-old girl.", "contents": "Infiltrating ductal carcinoma of the breast in the postpubertal adolescent: a case report. Infiltrating ductal carcinoma is an extremely rare neoplasm in the teenage or pre-teenage child. Routine pediatric physical examination should include careful examination of the breast and all palpable masses should be excised. Carcinoma occurring in the prepubertal child carries an improved prognosis particularly if the tumor stains PAS-positive. Carcinoma occurring in the postpubertal teenager probably carries the same prognosis as that in the adult and should be treated in a similar manner. The authors discuss such a case occurring in a 13-year-old girl."} {"id": "PMID:176913", "title": "Diagnostic accuracy of endoscopic retrograde cholangiopancreatography in hepatic, biliary, and pancreatic malignancy.", "content": "This paper reports the radiographic findings in 84 cases of biopsy-proven pancreatic and biliary malignancies studied by endoscopic retrograde cholangiopancreatography. In the 73 successful studies a diagnosis of tumor could be made in 67 patients (92%). The study was successful in 40 of 43 patients with pancreatic carcinoma and the diagnosis could be made in 37 on the basis of stenosis or obstruction of the ducts. There were 33 successful studies in the 41 patients with miscellaneous tumors including primary bile duct, ampullary, gallbladder, metastatic carcinoma, lymphoma, and hepatoma. A diagnosis of tumor was made in 30 studies. As has been observed in carcinoma of other hollow structures, the hallmark of malignancy in the pancreatic and biliary tract is obstruction and stenosis. This study indicates that malignant disease of the pancreas and tract is accurately assessed by this endoscopic method.", "contents": "Diagnostic accuracy of endoscopic retrograde cholangiopancreatography in hepatic, biliary, and pancreatic malignancy. This paper reports the radiographic findings in 84 cases of biopsy-proven pancreatic and biliary malignancies studied by endoscopic retrograde cholangiopancreatography. In the 73 successful studies a diagnosis of tumor could be made in 67 patients (92%). The study was successful in 40 of 43 patients with pancreatic carcinoma and the diagnosis could be made in 37 on the basis of stenosis or obstruction of the ducts. There were 33 successful studies in the 41 patients with miscellaneous tumors including primary bile duct, ampullary, gallbladder, metastatic carcinoma, lymphoma, and hepatoma. A diagnosis of tumor was made in 30 studies. As has been observed in carcinoma of other hollow structures, the hallmark of malignancy in the pancreatic and biliary tract is obstruction and stenosis. This study indicates that malignant disease of the pancreas and tract is accurately assessed by this endoscopic method."} {"id": "PMID:176915", "title": "Role of ionophores in energy coupling.", "content": "If, as we deem inevitable, the principles of energy coupling are universal, then the necessity for charge-separating devices will apply across the board to all bioenergetic systems. Since, apart from the elctron transfer chain, ionophores are the only charge-separating devices available in bioenergetic systems, model of energy coupling that does not feature this central role of ionophores can be taken seriously. The ionophore approach thus opens the royal highway to the ultimate solution of all bioenergetic problems.", "contents": "Role of ionophores in energy coupling. If, as we deem inevitable, the principles of energy coupling are universal, then the necessity for charge-separating devices will apply across the board to all bioenergetic systems. Since, apart from the elctron transfer chain, ionophores are the only charge-separating devices available in bioenergetic systems, model of energy coupling that does not feature this central role of ionophores can be taken seriously. The ionophore approach thus opens the royal highway to the ultimate solution of all bioenergetic problems."} {"id": "PMID:176917", "title": "[Adrenal cortex and avitaminosis A: II. Complementary in vivo and in vitro studies on inhibition of corticoidogenesis in moderate deficiency in the rat. III. In vivo criterion for activity: glycemic response to ACTH].", "content": "II. We set up new experiments, both in vivo and in vitro, in order to explain the impaired adrenal response to stress, of vitamin A middly deficient, male Wistar rats. Injections of progesterone, 6 mg s.c. or i.p. every other day, did not improve the deficiency curse in our rats. In agreement with these results, we have found that, in vitro, the delta5-3beta hydroxysteroide dehydrogenase is not altered in deficient glands; we confirmed it histochemically. On the other hand, the 11beta and 18 hydroxylase activities are lowered in vitro (and presumably in vivo). When conditions of hyperactivity are established, the conversion of deoxycorticosterone (DOC) to 18 OH-DOC or to corticosterone is reduced and DOC accumulates in the incubation medium. III. When middly deficient intact rats are injected with ACTH i.p. (2UI p. 100 g of body weight), only some of them are found to have normoglycemia or hyperglycemia, 45 or 60 minutes after injection, as the controls do. Many deficient rats become hypoglycemic as the adrenalectomised animals do. We think that the changes in the glycemia after ACTH injection could be used to discriminate between the more or less deficient rats.", "contents": "[Adrenal cortex and avitaminosis A: II. Complementary in vivo and in vitro studies on inhibition of corticoidogenesis in moderate deficiency in the rat. III. In vivo criterion for activity: glycemic response to ACTH]. II. We set up new experiments, both in vivo and in vitro, in order to explain the impaired adrenal response to stress, of vitamin A middly deficient, male Wistar rats. Injections of progesterone, 6 mg s.c. or i.p. every other day, did not improve the deficiency curse in our rats. In agreement with these results, we have found that, in vitro, the delta5-3beta hydroxysteroide dehydrogenase is not altered in deficient glands; we confirmed it histochemically. On the other hand, the 11beta and 18 hydroxylase activities are lowered in vitro (and presumably in vivo). When conditions of hyperactivity are established, the conversion of deoxycorticosterone (DOC) to 18 OH-DOC or to corticosterone is reduced and DOC accumulates in the incubation medium. III. When middly deficient intact rats are injected with ACTH i.p. (2UI p. 100 g of body weight), only some of them are found to have normoglycemia or hyperglycemia, 45 or 60 minutes after injection, as the controls do. Many deficient rats become hypoglycemic as the adrenalectomised animals do. We think that the changes in the glycemia after ACTH injection could be used to discriminate between the more or less deficient rats."} {"id": "PMID:176920", "title": "Current models of steroid hormone action: a critique.", "content": "In this review, we have traced the path of estradiol from its entry into the cell to the time of its release from the receptor. We feel that all of the current models are limited in one respect or another. We have examined most critically those currently most in vogue. The entry of estradiol into the cell is widely assumed to be simply a matter of diffusion. We have highlighted data that suggest the existence of a protein-mediated transport, but feel that the available data are too limited to make a definite conclusion.", "contents": "Current models of steroid hormone action: a critique. In this review, we have traced the path of estradiol from its entry into the cell to the time of its release from the receptor. We feel that all of the current models are limited in one respect or another. We have examined most critically those currently most in vogue. The entry of estradiol into the cell is widely assumed to be simply a matter of diffusion. We have highlighted data that suggest the existence of a protein-mediated transport, but feel that the available data are too limited to make a definite conclusion."} {"id": "PMID:176918", "title": "Carcinomatous encephalomyelitis with auditory and vestibular manifestations.", "content": "A clinical and pathological study of carcinomatous encephalomyelitis is presented. Attention is drawn to the various types of nonmetastatic paraneoplastic syndromes and their particular association with oat cell carcinoma of the lung. The feature of special interest in this study is the onset with otologic symptoms, sudden deafness in the left ear and vertigo, at a time when the neoplastic basis for the disease was not clinically evident. The most striking change in the left temporal bone is the almost total loss of cochlear neurons in Rosenthal's canal and degeneration of both divisions of the vestibular nerve. The organ of Corti and stria vascularis are normal throughout the cochlear duct. The vestibular sense organs are normal. The left cochlear nucleus is devoid of neurons, this neuronal loss is accompanied by a well developed astrocytic and microglial response similar to that in the medulla and spinal cord. This represents a carcinomatous sensory neuropathy involving the left VIII nerve with simultaneous involvement of the left cochlear nucleus. The pathogenesis of this condition still defies explanation, but there are some insights in the autoimmune sector.", "contents": "Carcinomatous encephalomyelitis with auditory and vestibular manifestations. A clinical and pathological study of carcinomatous encephalomyelitis is presented. Attention is drawn to the various types of nonmetastatic paraneoplastic syndromes and their particular association with oat cell carcinoma of the lung. The feature of special interest in this study is the onset with otologic symptoms, sudden deafness in the left ear and vertigo, at a time when the neoplastic basis for the disease was not clinically evident. The most striking change in the left temporal bone is the almost total loss of cochlear neurons in Rosenthal's canal and degeneration of both divisions of the vestibular nerve. The organ of Corti and stria vascularis are normal throughout the cochlear duct. The vestibular sense organs are normal. The left cochlear nucleus is devoid of neurons, this neuronal loss is accompanied by a well developed astrocytic and microglial response similar to that in the medulla and spinal cord. This represents a carcinomatous sensory neuropathy involving the left VIII nerve with simultaneous involvement of the left cochlear nucleus. The pathogenesis of this condition still defies explanation, but there are some insights in the autoimmune sector."} {"id": "PMID:176926", "title": "Susceptibility of beta-hemolytic streptococci to 65 antibacterial agents.", "content": "Tests for susceptibility of 29 group A, 4 group C, and 2 group G strains of beta-hemolytic streptococci to 63 antibiotics and to trimethoprim and sulfamethoxazole, singly and combined in a ratio of 1:16, were carried out in vitro. All strains tested were moderately or highly susceptible to all the antibiotics used except those belonging to the aminoglycoside and polymyxin groups. A few were also resistant to the tetracyclines and to sulfamethoxazole alone. Comparisons with results obtained in previous years indicate that, except for the tetracyclines and sulfonamides, there has been no change in the susceptibility of beta-hemolytic streptococci to the most important and useful antibiotics, particularly penicillin.", "contents": "Susceptibility of beta-hemolytic streptococci to 65 antibacterial agents. Tests for susceptibility of 29 group A, 4 group C, and 2 group G strains of beta-hemolytic streptococci to 63 antibiotics and to trimethoprim and sulfamethoxazole, singly and combined in a ratio of 1:16, were carried out in vitro. All strains tested were moderately or highly susceptible to all the antibiotics used except those belonging to the aminoglycoside and polymyxin groups. A few were also resistant to the tetracyclines and to sulfamethoxazole alone. Comparisons with results obtained in previous years indicate that, except for the tetracyclines and sulfonamides, there has been no change in the susceptibility of beta-hemolytic streptococci to the most important and useful antibiotics, particularly penicillin."} {"id": "PMID:176927", "title": "Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures.", "content": "The drug 9-beta-d-arabinofuranosyladenine (ara-A) significantly suppressed the formation of herpes simplex virus type 1-induced syncytia in BHK-21/4 cells at concentrations as low as 0.1 mug/ml. Optimal activity was noted when the drug was added before initiation of viral deoxyribonucleic acid (DNA) synthesis (3.5 h postinfection). The deaminated derivative of ara-A, 9-beta-d-arabinofuranosylhypoxanthine (ara-H), was at least 10 times less effective in suppressing the development of herpes simplex virus-induced syncytia. The replication of herpes simplex virus was measured by assaying fluids and cells from infected drug-treated cultures by using a plaque production technique. Ara-A at drug levels of >10 < 32 mug/ml completely blocked the replication of infectious virus particles. Ara-H was less effective than ara-A in reducing the replication of virions. Rates of host and viral DNA synthesis were monitored by pulse labeling herpes simplex virus-infected synchronized KB cells with [(3)H]thymidine and subsequently separating viral from cellular DNA in CsCl density gradients. During synthetic (S) phase, ara-A or ara-H at concentrations ranging from 3.2 to 32 mug/ml selectively inhibited viral DNA synthesis. At 3.2 mug of ara-A per ml, viral DNA synthesis was reduced 74% although total cellular DNA synthesis was unaffected. Increasing concentrations of ara-A produced increasing temporal delays in the maximal rate of host DNA synthesis. This time shift was not observed in cells treated with ara-H.", "contents": "Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. The drug 9-beta-d-arabinofuranosyladenine (ara-A) significantly suppressed the formation of herpes simplex virus type 1-induced syncytia in BHK-21/4 cells at concentrations as low as 0.1 mug/ml. Optimal activity was noted when the drug was added before initiation of viral deoxyribonucleic acid (DNA) synthesis (3.5 h postinfection). The deaminated derivative of ara-A, 9-beta-d-arabinofuranosylhypoxanthine (ara-H), was at least 10 times less effective in suppressing the development of herpes simplex virus-induced syncytia. The replication of herpes simplex virus was measured by assaying fluids and cells from infected drug-treated cultures by using a plaque production technique. Ara-A at drug levels of >10 < 32 mug/ml completely blocked the replication of infectious virus particles. Ara-H was less effective than ara-A in reducing the replication of virions. Rates of host and viral DNA synthesis were monitored by pulse labeling herpes simplex virus-infected synchronized KB cells with [(3)H]thymidine and subsequently separating viral from cellular DNA in CsCl density gradients. During synthetic (S) phase, ara-A or ara-H at concentrations ranging from 3.2 to 32 mug/ml selectively inhibited viral DNA synthesis. At 3.2 mug of ara-A per ml, viral DNA synthesis was reduced 74% although total cellular DNA synthesis was unaffected. Increasing concentrations of ara-A produced increasing temporal delays in the maximal rate of host DNA synthesis. This time shift was not observed in cells treated with ara-H."} {"id": "PMID:176928", "title": "Inhibition of herpesvirus deoxyribonucleic acid and protein synthesis by tilorone hydrochloride.", "content": "Tilorone hydrochloride at a concentration of 10 mug/ml very efficiently inhibited herpes simplex virus growth in BSC1 cells when the virus is infected at a low multiplicity of infection. The adsorption of the virus was not affected by the drug, and the penetration of the deoxyribonucleic acid of the input virus into the cytoplasm and nuclei proceeded normally when tilorone hydrochloride was present. However, newly synthesized viral deoxyribonucleic acid was not detectable under these conditions, there was a remarkable decrease in the rate of viral polypeptide synthesis, and virus particles were not formed. The inhibition of herpesvirus growth by tilorone hydrochloride was absolutely dependent on the presence of the drug in the cultures. Pretreatment of the cells with the drug did not result in resistance to herpesvirus infection after the removal of the drug.", "contents": "Inhibition of herpesvirus deoxyribonucleic acid and protein synthesis by tilorone hydrochloride. Tilorone hydrochloride at a concentration of 10 mug/ml very efficiently inhibited herpes simplex virus growth in BSC1 cells when the virus is infected at a low multiplicity of infection. The adsorption of the virus was not affected by the drug, and the penetration of the deoxyribonucleic acid of the input virus into the cytoplasm and nuclei proceeded normally when tilorone hydrochloride was present. However, newly synthesized viral deoxyribonucleic acid was not detectable under these conditions, there was a remarkable decrease in the rate of viral polypeptide synthesis, and virus particles were not formed. The inhibition of herpesvirus growth by tilorone hydrochloride was absolutely dependent on the presence of the drug in the cultures. Pretreatment of the cells with the drug did not result in resistance to herpesvirus infection after the removal of the drug."} {"id": "PMID:176929", "title": "Inhibition of Clostridium perfringens by an antibiotic substance produced by Bacillus licheniformis in the digestive tract of gnotobiotic mice: effect on other bacteria from the digestive tract.", "content": "A strain of Bacillus licheniformis, established in the digestive tract of gnotobiotic mice, inhibited the subsequent establishment of a Clostridium perfringens strain ingested by the animals. This inhibitory effect depended on the in vivo production by B. licheniformis of an antibiotic substance having a number of the characteristics of bacitracin. If C. perfringens was the first to become established in the digestive tract of the gnotobiotic mice, B. licheniformis also became established but did not produce any antibiotic. Mutants of C. perfringens resistant to the antibiotic substance were not observed when the antibiotic was produced in situ by B. licheniformis, but were rapidly selected when the Bacillus culture filtrate or bacitracin was administered per os. B. licheniformis was also capable of eliminating from the digestive tract 5 of the 13 additional bacterial strains tested.", "contents": "Inhibition of Clostridium perfringens by an antibiotic substance produced by Bacillus licheniformis in the digestive tract of gnotobiotic mice: effect on other bacteria from the digestive tract. A strain of Bacillus licheniformis, established in the digestive tract of gnotobiotic mice, inhibited the subsequent establishment of a Clostridium perfringens strain ingested by the animals. This inhibitory effect depended on the in vivo production by B. licheniformis of an antibiotic substance having a number of the characteristics of bacitracin. If C. perfringens was the first to become established in the digestive tract of the gnotobiotic mice, B. licheniformis also became established but did not produce any antibiotic. Mutants of C. perfringens resistant to the antibiotic substance were not observed when the antibiotic was produced in situ by B. licheniformis, but were rapidly selected when the Bacillus culture filtrate or bacitracin was administered per os. B. licheniformis was also capable of eliminating from the digestive tract 5 of the 13 additional bacterial strains tested."} {"id": "PMID:176930", "title": "Action of polymyxin B on bacterial membranes: phosphatidylglycerol- and cardiolipin-induced susceptibility to polymyxin B in Acholeplasma laidlawii B.", "content": "To identify the polymyxin receptor molecules in the membranes of living microorganisms, fusion of intact Acholeplasma laidlawii B with lipid vesicles was investigated according to the procedure of Grant and McConnell (1973). The naturally polymyxin-resistant A. laidlawii B was treated with phospholipid vesicles prepared from purified phospholipids of the polymyxin-susceptible Salmonella typhimurium G30. A. laidlawii B absorbed between 15 and 45% of its own lipid content of the added tritium-labeled phospholipids without loss of viability. Association with the acidic components phosphatidylglycerol and cardiolipin produced a 10- to 30-fold increase in polymyxin susceptibility, which was not obtained with egg-phosphatidylcholine and mixed phosphatidylcholine-phosphatidylethanolamine vesicles. The polymyxin-sensitized cells bound 12 times more radioactive antibiotic than resistant cells. The phosphatidylglycerol-induced susceptibility was abolished by serum fraction V (Cohn) proteins.", "contents": "Action of polymyxin B on bacterial membranes: phosphatidylglycerol- and cardiolipin-induced susceptibility to polymyxin B in Acholeplasma laidlawii B. To identify the polymyxin receptor molecules in the membranes of living microorganisms, fusion of intact Acholeplasma laidlawii B with lipid vesicles was investigated according to the procedure of Grant and McConnell (1973). The naturally polymyxin-resistant A. laidlawii B was treated with phospholipid vesicles prepared from purified phospholipids of the polymyxin-susceptible Salmonella typhimurium G30. A. laidlawii B absorbed between 15 and 45% of its own lipid content of the added tritium-labeled phospholipids without loss of viability. Association with the acidic components phosphatidylglycerol and cardiolipin produced a 10- to 30-fold increase in polymyxin susceptibility, which was not obtained with egg-phosphatidylcholine and mixed phosphatidylcholine-phosphatidylethanolamine vesicles. The polymyxin-sensitized cells bound 12 times more radioactive antibiotic than resistant cells. The phosphatidylglycerol-induced susceptibility was abolished by serum fraction V (Cohn) proteins."} {"id": "PMID:176931", "title": "Considerations on structure-activity relationships with mengovirus of substituted 5-amino-4-cyanopyrazoles.", "content": "In a screening program using the agar diffusion-plaque inhibition test, 22 out of 27 substituted aminopyrazoles tested showed marked antiviral activity against mengovirus in FL cell cultures. The efficacy of the different derivatives was compared by determining their effect on the yield of infectious virus after a one-step growth cycle. The antiviral activity against mengovirus correlated with the chain length of the substituents and increased or decreased according to the position of the side chain.", "contents": "Considerations on structure-activity relationships with mengovirus of substituted 5-amino-4-cyanopyrazoles. In a screening program using the agar diffusion-plaque inhibition test, 22 out of 27 substituted aminopyrazoles tested showed marked antiviral activity against mengovirus in FL cell cultures. The efficacy of the different derivatives was compared by determining their effect on the yield of infectious virus after a one-step growth cycle. The antiviral activity against mengovirus correlated with the chain length of the substituents and increased or decreased according to the position of the side chain."} {"id": "PMID:176932", "title": "Mode of action in vitro against mengovirus of substituted 5-amino-4-cyanopyrazoles.", "content": "Substituted amino pyrazoles were found to exhibit plaque reduction and inhibition of the cytopathic effect of mengovirus on FL cells. Their antiviral activity was not caused by a virucidal effect or by inhibition of viral adsoprtion or penetration but by suppression of the virus multiplication. During a one-step growth cycle maximum suppression of virus yield occurred after compound addition from 0 to 2 h after infection. Progressively less viral inhibition appeared when compound was applied during the later part of virus replication. The antiviral effect was reversible by removal of the compound, and no inhibitor-resistant period occurred.", "contents": "Mode of action in vitro against mengovirus of substituted 5-amino-4-cyanopyrazoles. Substituted amino pyrazoles were found to exhibit plaque reduction and inhibition of the cytopathic effect of mengovirus on FL cells. Their antiviral activity was not caused by a virucidal effect or by inhibition of viral adsoprtion or penetration but by suppression of the virus multiplication. During a one-step growth cycle maximum suppression of virus yield occurred after compound addition from 0 to 2 h after infection. Progressively less viral inhibition appeared when compound was applied during the later part of virus replication. The antiviral effect was reversible by removal of the compound, and no inhibitor-resistant period occurred."} {"id": "PMID:176933", "title": "Use of sodium polyanethol sulfonate to selectively inhibit aminoglycoside and polymyxin antibiotics in a rapid blood level antibiotic assay.", "content": "Sodium polyanethol sulfonate inhibits aminoglycoside and polymyxin classes of antibiotics in direct proportion to its concentration. Aminoglycoside and polymyxin class antibiotics are selectively inactivated; penicillin, including the semisynthetic penicillins, cephalothin, chloramphenicol, clindamycin, tetracycline, erythromycin, and vancomycin are not inhibited. By incorporating sodium polyanethol sulfonate directly into the test medium it is possible, in a 4-h antibiotic blood level assay, to selectively obviate the activity of the aminoglycosides and polymyxins to determine the concentration of other antibiotics present in the same serum sample.", "contents": "Use of sodium polyanethol sulfonate to selectively inhibit aminoglycoside and polymyxin antibiotics in a rapid blood level antibiotic assay. Sodium polyanethol sulfonate inhibits aminoglycoside and polymyxin classes of antibiotics in direct proportion to its concentration. Aminoglycoside and polymyxin class antibiotics are selectively inactivated; penicillin, including the semisynthetic penicillins, cephalothin, chloramphenicol, clindamycin, tetracycline, erythromycin, and vancomycin are not inhibited. By incorporating sodium polyanethol sulfonate directly into the test medium it is possible, in a 4-h antibiotic blood level assay, to selectively obviate the activity of the aminoglycosides and polymyxins to determine the concentration of other antibiotics present in the same serum sample."} {"id": "PMID:176934", "title": "Stimulation of murine interferon by a substituted pyrimidine.", "content": "2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166) induced high levels of circulating interferon in mice when administered either parenterally or orally. Peak titers of interferon were found in the serum between 6 and 12 h after inoculation of the drug. Lower but significant levels of interferon were found in rat serum after administration of U-25,166 by either the intraperitoneal or oral route, and good levels of circulating interferon were observed in cats after oral treatment. Repeated intraperitoneal doses (50 mg/kg) of U-25,166 protected mice against intranasal encephalomyocarditis virus challenge. The minimal effective acute oral dose for antiviral activity was approximately 250 mg/kg. This was also the minimal dose that produced detectable levels of interferon. Maximum tolerated doses in mice were four to six times the minimal effective doses. A single oral treatment was protective in mice against challenge virus inoculated 24 h later. The compound protected mice from challenge with high levels of encephalomyocarditis virus, up to 20,000 mean lethal doses. Antiviral activity in mice was retained when certain minor substitutions were made in the U-25,166 structure.", "contents": "Stimulation of murine interferon by a substituted pyrimidine. 2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166) induced high levels of circulating interferon in mice when administered either parenterally or orally. Peak titers of interferon were found in the serum between 6 and 12 h after inoculation of the drug. Lower but significant levels of interferon were found in rat serum after administration of U-25,166 by either the intraperitoneal or oral route, and good levels of circulating interferon were observed in cats after oral treatment. Repeated intraperitoneal doses (50 mg/kg) of U-25,166 protected mice against intranasal encephalomyocarditis virus challenge. The minimal effective acute oral dose for antiviral activity was approximately 250 mg/kg. This was also the minimal dose that produced detectable levels of interferon. Maximum tolerated doses in mice were four to six times the minimal effective doses. A single oral treatment was protective in mice against challenge virus inoculated 24 h later. The compound protected mice from challenge with high levels of encephalomyocarditis virus, up to 20,000 mean lethal doses. Antiviral activity in mice was retained when certain minor substitutions were made in the U-25,166 structure."} {"id": "PMID:176935", "title": "Effect of cytosine arabinoside and 5-iodo-2'-deoxyuridine on a cytomegalovirus infection in newborn mice.", "content": "Murine cytomegalovirus was inhibited by 0.6 to 1.2 mug of cytosine arabinoside per ml and by 0.3 to 0.6 mug of 5-iodo-2'-deoxyuridine in mouse embryo fibroblast cells. Human cytomegalovirus was inhibited by similar concentrations of the two drugs in WI-38 cells. Intraperitoneal inoculation of suckling mice with 10(4.5) plaque-forming units of murine cytomegalovirus provides a model for disseminated human cytomegalovirus infection in human newborn infants and is characterized by a widespread infection involving the liver, spleen, lung, kidney, and brain with a 70 to 90% mortality in 7 to 9 days. Treatment with 12.5 mg of cytosine arabinoside per kg or 25 mg of 5-iodo-2'-deoxyuridine per kg twice daily for 8 days had no effect on final mortality or the pathogenesis of the infection with the exception of reduced viral titers in the spleen of 5-iodo-2'-deoxyuridine-treated animals. These data indicate that neither cytosine arabinoside nor 5-iodo-2'-deoxyuridine are effective in the treatment of murine cytomegalovirus infections in suckling mice and suggest that they may be of limited value in the treatment of severe cytomegalovirus infections in human neonates.", "contents": "Effect of cytosine arabinoside and 5-iodo-2'-deoxyuridine on a cytomegalovirus infection in newborn mice. Murine cytomegalovirus was inhibited by 0.6 to 1.2 mug of cytosine arabinoside per ml and by 0.3 to 0.6 mug of 5-iodo-2'-deoxyuridine in mouse embryo fibroblast cells. Human cytomegalovirus was inhibited by similar concentrations of the two drugs in WI-38 cells. Intraperitoneal inoculation of suckling mice with 10(4.5) plaque-forming units of murine cytomegalovirus provides a model for disseminated human cytomegalovirus infection in human newborn infants and is characterized by a widespread infection involving the liver, spleen, lung, kidney, and brain with a 70 to 90% mortality in 7 to 9 days. Treatment with 12.5 mg of cytosine arabinoside per kg or 25 mg of 5-iodo-2'-deoxyuridine per kg twice daily for 8 days had no effect on final mortality or the pathogenesis of the infection with the exception of reduced viral titers in the spleen of 5-iodo-2'-deoxyuridine-treated animals. These data indicate that neither cytosine arabinoside nor 5-iodo-2'-deoxyuridine are effective in the treatment of murine cytomegalovirus infections in suckling mice and suggest that they may be of limited value in the treatment of severe cytomegalovirus infections in human neonates."} {"id": "PMID:176936", "title": "In vitro and in vivo activities of minocycline and other antibiotics against Acinetobacter (Herellea-Mima).", "content": "Minocycline was the most active of six antibiotics tested against 65 clinical isolates of Acinetobacter calcoaceticus (syn.: Herellea, Mima) received from six medical centers. In the Bauer-Kirby disk susceptibility test, all isolates were rated susceptible to minocycline, gentamicin, and polymyxin; 25% were resistant to tetracycline. In agar dilution tests, minocycline was two to four times more potent than gentamicin or polymyxin and eight times more potent than tetracycline. Ampicillin and cephalexin were relatively ineffective. Against lethal infections produced by five strains of A. calcoaceticus in mice, minocycline was, in general, more active than gentamicin or polymyxin on a dosage basis and significantly more active on a blood-level basis. Minocycline was significantly more potent than tetracycline on both dosage and blood-level bases against tetracycline-sensitive and -resistant strains. In the last decade there has been an increase in the reported incidence of acinetobacters in a variety of infections. The cultures are susceptible to few antibiotics. Our data show that minocycline could offer an effective alternative to the more toxic drugs for the treatment of these infections. Susceptibility should be determined with minocycline disks.", "contents": "In vitro and in vivo activities of minocycline and other antibiotics against Acinetobacter (Herellea-Mima). Minocycline was the most active of six antibiotics tested against 65 clinical isolates of Acinetobacter calcoaceticus (syn.: Herellea, Mima) received from six medical centers. In the Bauer-Kirby disk susceptibility test, all isolates were rated susceptible to minocycline, gentamicin, and polymyxin; 25% were resistant to tetracycline. In agar dilution tests, minocycline was two to four times more potent than gentamicin or polymyxin and eight times more potent than tetracycline. Ampicillin and cephalexin were relatively ineffective. Against lethal infections produced by five strains of A. calcoaceticus in mice, minocycline was, in general, more active than gentamicin or polymyxin on a dosage basis and significantly more active on a blood-level basis. Minocycline was significantly more potent than tetracycline on both dosage and blood-level bases against tetracycline-sensitive and -resistant strains. In the last decade there has been an increase in the reported incidence of acinetobacters in a variety of infections. The cultures are susceptible to few antibiotics. Our data show that minocycline could offer an effective alternative to the more toxic drugs for the treatment of these infections. Susceptibility should be determined with minocycline disks."} {"id": "PMID:176937", "title": "In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside.", "content": "The in vitro susceptibility of varicella zoster (VZ) isolates to adenine arabinoside (ara-A) and hypoxanthine arabinoside (ara-Hx) was determined in human skin fibroblasts. Using a system in which deamination was inhibited, and using a modified plaque reduction method, the antiviral activities of ara-A and ara-Hx were separated. The plaque inhibitory concentration of ara-A for all VZ isolates tested was 1 to 2 mug/ml and 80 to 100 mug/ml for ara-Hx. A comparison of antiviral activity based upon total plaque suppression gave a rate of 40 to 50:1, in favor of ara-A.", "contents": "In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside. The in vitro susceptibility of varicella zoster (VZ) isolates to adenine arabinoside (ara-A) and hypoxanthine arabinoside (ara-Hx) was determined in human skin fibroblasts. Using a system in which deamination was inhibited, and using a modified plaque reduction method, the antiviral activities of ara-A and ara-Hx were separated. The plaque inhibitory concentration of ara-A for all VZ isolates tested was 1 to 2 mug/ml and 80 to 100 mug/ml for ara-Hx. A comparison of antiviral activity based upon total plaque suppression gave a rate of 40 to 50:1, in favor of ara-A."} {"id": "PMID:176938", "title": "Microbial metabolism of aryl sulphonates a re-assessment of colorimetric methods for the determination of sulphite and their use in measuring desulphonation of aryl and alkylbenzene sulphonates.", "content": "The reaction of 2,4-dinitroanilinomaleimide with sulphite which has been claimed as the basis of a suitable colorimetric assay for the anion was carefully re-examined. The sulphite-imide addition product provides a suitable and specific qualitative test for sulphite after separation by paper chromatography but the method as previously used is probably measuring the hydrolysis of the imide to 2,4-dinitroanilinomaleamic acid and cannot be used for sulphite determination either colorimetrically or in kinetic assays. A new colorimetric method for the determination of sulphite based on its reaction with Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid) is described and compared for sensitivity with the p-rosaniline-HCHO method. Both methods were used to show the formation of sulphite as the initial product of arylsulphonate metabolism by bacteria. The failure to find sulphite in similar cultures of a third organism was attributed to the very high activities of sulphite oxidase found in extracts. The Ellman reagent was examined as the basis of an indicator medium for the detection of sulphite-excreting colonies.", "contents": "Microbial metabolism of aryl sulphonates a re-assessment of colorimetric methods for the determination of sulphite and their use in measuring desulphonation of aryl and alkylbenzene sulphonates. The reaction of 2,4-dinitroanilinomaleimide with sulphite which has been claimed as the basis of a suitable colorimetric assay for the anion was carefully re-examined. The sulphite-imide addition product provides a suitable and specific qualitative test for sulphite after separation by paper chromatography but the method as previously used is probably measuring the hydrolysis of the imide to 2,4-dinitroanilinomaleamic acid and cannot be used for sulphite determination either colorimetrically or in kinetic assays. A new colorimetric method for the determination of sulphite based on its reaction with Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid) is described and compared for sensitivity with the p-rosaniline-HCHO method. Both methods were used to show the formation of sulphite as the initial product of arylsulphonate metabolism by bacteria. The failure to find sulphite in similar cultures of a third organism was attributed to the very high activities of sulphite oxidase found in extracts. The Ellman reagent was examined as the basis of an indicator medium for the detection of sulphite-excreting colonies."} {"id": "PMID:176958", "title": "Activation of human leucocyte procollagenase by rheumatoid synovial tissue culture medium.", "content": "Production of a factor activating leucocyte procollagenase by tissue culture of rheumatoid synovium was shown. The activator was isolated, partly purified, and shown to be thermolabile, nondialysable, and had no activity toward casein, haemoglobin, histones, and PZ-peptide. The activity of the activator was partly decreased by trypsin.", "contents": "Activation of human leucocyte procollagenase by rheumatoid synovial tissue culture medium. Production of a factor activating leucocyte procollagenase by tissue culture of rheumatoid synovium was shown. The activator was isolated, partly purified, and shown to be thermolabile, nondialysable, and had no activity toward casein, haemoglobin, histones, and PZ-peptide. The activity of the activator was partly decreased by trypsin."} {"id": "PMID:176959", "title": "Benign liver cell adenoma associated with use of oral contraceptive agents.", "content": "A benign hepatic adenoma in a young woman taking oral contraceptives for 7 years is reported. The diagnosis must be suspected in any young woman taking oral contraceptive agents who develop signs and symptoms of acute cholecystitis with hepatomegaly or mass, or when signs and symptoms of non-traumatic intraabdominal hemorrhage are present. Rupture of the tumor is a life-threatening complication. Treatment should be either hepatic lobectomy or wide local resection.", "contents": "Benign liver cell adenoma associated with use of oral contraceptive agents. A benign hepatic adenoma in a young woman taking oral contraceptives for 7 years is reported. The diagnosis must be suspected in any young woman taking oral contraceptive agents who develop signs and symptoms of acute cholecystitis with hepatomegaly or mass, or when signs and symptoms of non-traumatic intraabdominal hemorrhage are present. Rupture of the tumor is a life-threatening complication. Treatment should be either hepatic lobectomy or wide local resection."} {"id": "PMID:176961", "title": "Cyclic adenosinemonophosphate in cerebrospinal fluid. Effects of theophylline, L-dopa and a dopamine receptor stimulant in rats.", "content": "The effects of L-Dopa and the dopamine receptor stimulant ET-495 on cisternal cAMP levels were studied in rats. L-dopa (100-200 mg/kg) increased cisternal cAMP levels by 60 to 80% of controls. When peripheral Dopa-decarboxylase was inhibited, smaller doses of L-Dopa were effective. Fla-63, an inhibitor of dopamine-beta-hydroxylase lowered the increase induced by L-Dopa which was completely suppressed by propranolol, not by phentolamine, suggesting that the cAMP increase is mediated through a central beta-adrenoceptor stimulation. ET-495 failed to influence cAMP levels which argues against a dopamine-sensitive adenylate cyclase involved in the L-Dopa effect. Moreover, large increases of cisternal cAMP were observed after treatment with theophylline , not papaverine which suggests different effects of these \"phosphodiesterase inhibitors\" on the cyclic AMP systems in the central nervous system or on transport mechanisms.", "contents": "Cyclic adenosinemonophosphate in cerebrospinal fluid. Effects of theophylline, L-dopa and a dopamine receptor stimulant in rats. The effects of L-Dopa and the dopamine receptor stimulant ET-495 on cisternal cAMP levels were studied in rats. L-dopa (100-200 mg/kg) increased cisternal cAMP levels by 60 to 80% of controls. When peripheral Dopa-decarboxylase was inhibited, smaller doses of L-Dopa were effective. Fla-63, an inhibitor of dopamine-beta-hydroxylase lowered the increase induced by L-Dopa which was completely suppressed by propranolol, not by phentolamine, suggesting that the cAMP increase is mediated through a central beta-adrenoceptor stimulation. ET-495 failed to influence cAMP levels which argues against a dopamine-sensitive adenylate cyclase involved in the L-Dopa effect. Moreover, large increases of cisternal cAMP were observed after treatment with theophylline , not papaverine which suggests different effects of these \"phosphodiesterase inhibitors\" on the cyclic AMP systems in the central nervous system or on transport mechanisms."} {"id": "PMID:176962", "title": "Intrathoracic paraganglioma arising from aorticosympathetic paraganglion.", "content": "A slowly growing intrathoracic paraganglion arising from an aorticosympathetic ganglion was removed from a 22-year-old woman. It was adherent to the parietal pleura and azygos vein, but not to the spinal cord. She has been well for the two years since that time. This patient represents the sixth tumor reported in this location. Most of the reported tumors are benign with occasional local invasion as seen in paragangliomas in other locations (carotid and aortic bodies). Complete excision of the tumor is the treatment of choice, but partial excision may provide long-term survival. A new classification and terminology suggested by Glenner and Grimley is emphasized. It groups logically the tumors arising from the paraganglion cells on the basis of anatomic distribution, innervation, and microscopic structure.", "contents": "Intrathoracic paraganglioma arising from aorticosympathetic paraganglion. A slowly growing intrathoracic paraganglion arising from an aorticosympathetic ganglion was removed from a 22-year-old woman. It was adherent to the parietal pleura and azygos vein, but not to the spinal cord. She has been well for the two years since that time. This patient represents the sixth tumor reported in this location. Most of the reported tumors are benign with occasional local invasion as seen in paragangliomas in other locations (carotid and aortic bodies). Complete excision of the tumor is the treatment of choice, but partial excision may provide long-term survival. A new classification and terminology suggested by Glenner and Grimley is emphasized. It groups logically the tumors arising from the paraganglion cells on the basis of anatomic distribution, innervation, and microscopic structure."} {"id": "PMID:176963", "title": "Cystosarcoma phyllodes metastatic to a brenner tumor of the ovary.", "content": "A patient had cytosarcoma phyllodes that developed metastases to bone and to a Brenner tumor of the ovary. The original breast tumor was reported as benign, but the patient died of metastases four months following mastectomy. The rapid growth in the ovary may have been due to estrogenic stroma in the Brenner tumor. This is the first report, to our knowledge, of cystosarcoma phyllodes metastasizing to another tumor.", "contents": "Cystosarcoma phyllodes metastatic to a brenner tumor of the ovary. A patient had cytosarcoma phyllodes that developed metastases to bone and to a Brenner tumor of the ovary. The original breast tumor was reported as benign, but the patient died of metastases four months following mastectomy. The rapid growth in the ovary may have been due to estrogenic stroma in the Brenner tumor. This is the first report, to our knowledge, of cystosarcoma phyllodes metastasizing to another tumor."} {"id": "PMID:176960", "title": "[Study of cortico-melanotropic activities in the anterior pituitary of an anencephalic and a normal newborn].", "content": "Immunofluorescence studies by-means of anti-beta (1-24) corticotropin, anti-alpha (17-39) ACTH; anti-beta-MSH were performed on the anterior pituitary of an at-term anencephalic newborn. They showed small and rare cortico-melanotropic cells, as compared to those seen in the anterior pituitary of newborns. The comparison of these data with experimental observations suggest a possible autonomy of corticotropin function, although under hypothalamus control.", "contents": "[Study of cortico-melanotropic activities in the anterior pituitary of an anencephalic and a normal newborn]. Immunofluorescence studies by-means of anti-beta (1-24) corticotropin, anti-alpha (17-39) ACTH; anti-beta-MSH were performed on the anterior pituitary of an at-term anencephalic newborn. They showed small and rare cortico-melanotropic cells, as compared to those seen in the anterior pituitary of newborns. The comparison of these data with experimental observations suggest a possible autonomy of corticotropin function, although under hypothalamus control."} {"id": "PMID:176964", "title": "Grafting the unhealed perineal wound after coloproctectomy for Crohn disease.", "content": "The unhealed perineal wound following proctectomy for Crohn disease is a most unfortunate and disabling complication; treatment has been generally unsuccessful and disappointing. Since 1967, we have managed these wounds by skin-grafting the raw surface of the saucerized wound, rather than by attempting to obliterate the cavity. The graft is applied to the defect two or three days after wide debridement and saucerization. No attempt is made to cover more than the readily accessible raw surface. The graft is first dressed on the third postoperative day, and daily thereafter. The patient receives 40 units of corticotropin (ACTH) daily during his hospital stay; the drug therapy is continued in smaller dosage for several months. Results to date have been satisfactory, with seven wounds totally dry, and 37 resurfaced sufficiently so as to make the amount of drainage negligible. Four patients had results classified as poor.", "contents": "Grafting the unhealed perineal wound after coloproctectomy for Crohn disease. The unhealed perineal wound following proctectomy for Crohn disease is a most unfortunate and disabling complication; treatment has been generally unsuccessful and disappointing. Since 1967, we have managed these wounds by skin-grafting the raw surface of the saucerized wound, rather than by attempting to obliterate the cavity. The graft is applied to the defect two or three days after wide debridement and saucerization. No attempt is made to cover more than the readily accessible raw surface. The graft is first dressed on the third postoperative day, and daily thereafter. The patient receives 40 units of corticotropin (ACTH) daily during his hospital stay; the drug therapy is continued in smaller dosage for several months. Results to date have been satisfactory, with seven wounds totally dry, and 37 resurfaced sufficiently so as to make the amount of drainage negligible. Four patients had results classified as poor."} {"id": "PMID:176965", "title": "The use of chicken tracheal organ cultures for the isolation and assay of avian infectious bronchitis virus.", "content": "A study has been made of the use of chicken tracheal organ cultures for the isolation and assay of avian infectious bronchitis (AIB) virus from both naturally and experimentally infected chickens. Six strains of AIB virus were investigated, 3 of which had been isolated from natural outbreaks of disease. Two of the virus isolations from the outbreaks of AIB were made directly into tracheal organ cultures without passage in embryonated eggs. Organ cultures prepared from 20-day-old embryos were used since they were found to be somewhat more sensitive in virus assay than those derived from chickens of up to 31 days of age. Ciliostasis, which was used as the marker of infectivity, was complete by 3 days after inoculation with each strain of virus examined. Virus could be isolated from both respiratory and non-respiratory tissue in tracheal organ cultures and these cultures were found to be at least as sensitive as 9-day-old embryonated eggs in detecting AIB virus either in pathological material or in serial dilutions. When virus was assayed in both systems, the titres were very similar. It is considered, therefore, that chicken embryo tracheal organ cultures offer a reliable alternative system to embryonated eggs for studying AIB virus.", "contents": "The use of chicken tracheal organ cultures for the isolation and assay of avian infectious bronchitis virus. A study has been made of the use of chicken tracheal organ cultures for the isolation and assay of avian infectious bronchitis (AIB) virus from both naturally and experimentally infected chickens. Six strains of AIB virus were investigated, 3 of which had been isolated from natural outbreaks of disease. Two of the virus isolations from the outbreaks of AIB were made directly into tracheal organ cultures without passage in embryonated eggs. Organ cultures prepared from 20-day-old embryos were used since they were found to be somewhat more sensitive in virus assay than those derived from chickens of up to 31 days of age. Ciliostasis, which was used as the marker of infectivity, was complete by 3 days after inoculation with each strain of virus examined. Virus could be isolated from both respiratory and non-respiratory tissue in tracheal organ cultures and these cultures were found to be at least as sensitive as 9-day-old embryonated eggs in detecting AIB virus either in pathological material or in serial dilutions. When virus was assayed in both systems, the titres were very similar. It is considered, therefore, that chicken embryo tracheal organ cultures offer a reliable alternative system to embryonated eggs for studying AIB virus."} {"id": "PMID:176966", "title": "In-vitro cultivation of human cytomegalovirus in thyroid epithelial cells.", "content": "Several strains of human cytomegalovirus including recent isolates, were grown in epithelial cells derived from thyroid tissue. All the strains tested grew in these cultures without pre-treatment of the cells, and no difference in cytopathic effect was detected between strains of genital and non-genital origin. 4 strains of CMV were isolated directly from urine in thyroid cells; however the failure to isolate 6 further strains in these cultures from other specimens may indicate that a higher multiplicity of infection is required to infect epithelial than fibroblast cells.", "contents": "In-vitro cultivation of human cytomegalovirus in thyroid epithelial cells. Several strains of human cytomegalovirus including recent isolates, were grown in epithelial cells derived from thyroid tissue. All the strains tested grew in these cultures without pre-treatment of the cells, and no difference in cytopathic effect was detected between strains of genital and non-genital origin. 4 strains of CMV were isolated directly from urine in thyroid cells; however the failure to isolate 6 further strains in these cultures from other specimens may indicate that a higher multiplicity of infection is required to infect epithelial than fibroblast cells."} {"id": "PMID:176967", "title": "Simian virus 40-chinese hamster kidney cell interaction. II. The semipermissivity of the cell system.", "content": "Throughout in vitro passages, Chinese hamster kidney (CHK) cells progressively lost susceptibility to SV 40 virus infection while remaining continuously susceptible to viral DNA infection. Upon infection with SV 40 virus or viral DNA, the CHK cell line supported viral DNA and virus replication at a low level. SV 40 transformed CHK cell lines spontaneously produced small amounts of viral DNA and virions. The percentage of virus-producing cells was low. Various clones derived from each of these lines behaved as the parental cell population, leading to the conclusion that each CHK cell, whether transformed or not with SV 40, is potentially permissive for this virus.", "contents": "Simian virus 40-chinese hamster kidney cell interaction. II. The semipermissivity of the cell system. Throughout in vitro passages, Chinese hamster kidney (CHK) cells progressively lost susceptibility to SV 40 virus infection while remaining continuously susceptible to viral DNA infection. Upon infection with SV 40 virus or viral DNA, the CHK cell line supported viral DNA and virus replication at a low level. SV 40 transformed CHK cell lines spontaneously produced small amounts of viral DNA and virions. The percentage of virus-producing cells was low. Various clones derived from each of these lines behaved as the parental cell population, leading to the conclusion that each CHK cell, whether transformed or not with SV 40, is potentially permissive for this virus."} {"id": "PMID:176968", "title": "Electron microscope observations on tubular structures in cells infected with herpes simplex virus type 2.", "content": "The fine structure of filamentous structures and lattice-like structures found in herpes simplex virus type 2-infected cells was studied. By specimen tilting experiments, it was demonstrated that the lattice-like structures were the cross-sectional views of the tubular structures and the filamentous structures were the longitudinal sections. The observation in negatively stained preparations of isolated tubular structures revealed that the structure was constructed by regular array of ring shaped elements. A hypothetical model is presented for tubular structures constructed on the basis of the present findings. The tubular structures appeared as early as 6 hours after infection and reached a maximum at 12 hours.", "contents": "Electron microscope observations on tubular structures in cells infected with herpes simplex virus type 2. The fine structure of filamentous structures and lattice-like structures found in herpes simplex virus type 2-infected cells was studied. By specimen tilting experiments, it was demonstrated that the lattice-like structures were the cross-sectional views of the tubular structures and the filamentous structures were the longitudinal sections. The observation in negatively stained preparations of isolated tubular structures revealed that the structure was constructed by regular array of ring shaped elements. A hypothetical model is presented for tubular structures constructed on the basis of the present findings. The tubular structures appeared as early as 6 hours after infection and reached a maximum at 12 hours."} {"id": "PMID:176969", "title": "Heterogeneity of infectious bronchitis virus grown in eggs.", "content": "Egg-grown infectious bronchitis virus, strain Beaudette, was concentrated and centrifuged on sucrose density gradients to separate the virus into five peaks with densities of 1.144, 1.160, 1.172, 1.191 and 1.218 g/cm3. All peaks retained infectivity, complement fixation activity and were labelled with 3H-uridine. Morphologically the densest peak consisted of very large virus particles and amorphous material, the other peaks consisted of mainly intact particles although small differences in size and pleomorphism were seen. Polyacrylamide gel electrophoresis of material from the density gradient peaks revealed four major polypeptides and at least 10 minor polypeptides. The proportions of the polypeptides were approximately similar for all peaks with the exception of the densest peak in which the major polypeptides were greatly reduced. The four major polypeptides had approximate molecular weights of 1. 52,000, 2. 45,000, 3. 34,000, 4. 32,000. The major polypeptides 1 and 4 were shown to be glycosylated as were two of the minor polypeptides.", "contents": "Heterogeneity of infectious bronchitis virus grown in eggs. Egg-grown infectious bronchitis virus, strain Beaudette, was concentrated and centrifuged on sucrose density gradients to separate the virus into five peaks with densities of 1.144, 1.160, 1.172, 1.191 and 1.218 g/cm3. All peaks retained infectivity, complement fixation activity and were labelled with 3H-uridine. Morphologically the densest peak consisted of very large virus particles and amorphous material, the other peaks consisted of mainly intact particles although small differences in size and pleomorphism were seen. Polyacrylamide gel electrophoresis of material from the density gradient peaks revealed four major polypeptides and at least 10 minor polypeptides. The proportions of the polypeptides were approximately similar for all peaks with the exception of the densest peak in which the major polypeptides were greatly reduced. The four major polypeptides had approximate molecular weights of 1. 52,000, 2. 45,000, 3. 34,000, 4. 32,000. The major polypeptides 1 and 4 were shown to be glycosylated as were two of the minor polypeptides."} {"id": "PMID:176970", "title": "Characterization of cell lines derived from hamster tumors induced with the BK virus.", "content": "Some of the properties of three continuous cell lines derived from BK virus-induced hamster tumors were examined. The cell lines had in vitro growth characteristics of transformed cells. Morphologically most of the cells were fibroblastic, but multinucleated giant cells were also common. Ultrastructurally all three cell lines displayed the usual features of cells grown in vitro. Marked variation in the nuclear size and shape as well as prominent nucleoli were characteristic to these cells. No viruses or virus-like particles were found. Virus isolation attempts by fusing the cells with Vero cells were negative, and no virion antigen was detected in these cells by immunofluorescence. T antigen similar to that of other papovaviruses was found in the cells. This antigen stained with sera from a number of hamsters carrying transplanted BK virus-induced tumors, and also with SV 40 T antisera. The antigen disappeared after 30 minutes at 56 degrees C. Cytogenetic analyses showed that the three cell lines were heteroploid with subtetraploid numbers of chromosomes. Chromosome abnormalities were also seen. All three cell lines induced sarcomatous tumors in adult hamsters after subcutaneous inoculation.", "contents": "Characterization of cell lines derived from hamster tumors induced with the BK virus. Some of the properties of three continuous cell lines derived from BK virus-induced hamster tumors were examined. The cell lines had in vitro growth characteristics of transformed cells. Morphologically most of the cells were fibroblastic, but multinucleated giant cells were also common. Ultrastructurally all three cell lines displayed the usual features of cells grown in vitro. Marked variation in the nuclear size and shape as well as prominent nucleoli were characteristic to these cells. No viruses or virus-like particles were found. Virus isolation attempts by fusing the cells with Vero cells were negative, and no virion antigen was detected in these cells by immunofluorescence. T antigen similar to that of other papovaviruses was found in the cells. This antigen stained with sera from a number of hamsters carrying transplanted BK virus-induced tumors, and also with SV 40 T antisera. The antigen disappeared after 30 minutes at 56 degrees C. Cytogenetic analyses showed that the three cell lines were heteroploid with subtetraploid numbers of chromosomes. Chromosome abnormalities were also seen. All three cell lines induced sarcomatous tumors in adult hamsters after subcutaneous inoculation."} {"id": "PMID:176971", "title": "Ultrastructural characterization and hepatic pathogenesis of duck plague virus.", "content": "Six-week-old white Pekin ducks were inoculated intravenously with duck plague virus (DPV) isolated from wild waterfowl. The virus replicated in hepatic macrophages, hepatocytes, and bile duct epithelium. In ultrathin sections, herpes-like nucleocapsids and virions were found respectively in the nucleus and cytoplasm of infected cells. Typical herpesviral capsids and virions were seen in negatively-stained preparations of duck embryo fibroblasts. Antibodies against Holland-attenuated strain of DPV reacted with virions of this isolate.", "contents": "Ultrastructural characterization and hepatic pathogenesis of duck plague virus. Six-week-old white Pekin ducks were inoculated intravenously with duck plague virus (DPV) isolated from wild waterfowl. The virus replicated in hepatic macrophages, hepatocytes, and bile duct epithelium. In ultrathin sections, herpes-like nucleocapsids and virions were found respectively in the nucleus and cytoplasm of infected cells. Typical herpesviral capsids and virions were seen in negatively-stained preparations of duck embryo fibroblasts. Antibodies against Holland-attenuated strain of DPV reacted with virions of this isolate."} {"id": "PMID:176972", "title": "[Electron microscopy studies of the early stages of mosquito cell infection in vitro by the chilo iridescent virus and the infectious bovine rhinotracheitis (author's transl)].", "content": "The early stage of the viral infection in vitro of mosquito cells were studied by electron microscopy using a microculture technique. We demonstrate in this paper that two viruses: iridescent (CIV) and herpetic (Infectious bovine rhinotracheitis) can enter by viropexis and be uncoated in several lines of mosquito cells.", "contents": "[Electron microscopy studies of the early stages of mosquito cell infection in vitro by the chilo iridescent virus and the infectious bovine rhinotracheitis (author's transl)]. The early stage of the viral infection in vitro of mosquito cells were studied by electron microscopy using a microculture technique. We demonstrate in this paper that two viruses: iridescent (CIV) and herpetic (Infectious bovine rhinotracheitis) can enter by viropexis and be uncoated in several lines of mosquito cells."} {"id": "PMID:176973", "title": "Cell-mediated immunity in Aujeszky disease virus infected pigs. I. Lymphocyte stimulation.", "content": "The appearance of cell-mediated immunity was studied in Aujeszky diseased pigs with the aid of the in vitro stimulation of sensitized lymphocytes. The first cell-mediated immunity reaction of lymphocytes occurred 4 days after infection. From day 7 to 35, the latest day tested, the reactions were most marked with lymphocytes from lymph nodes and spleen, whereas blood and thymus lymphocytes reacted less frequently; bone marrow lymphocytes showed no response. Reinfection did not considerably enhance lymphocyte reactivity. Humoral immunity was demonstrated a few days later than cell-mediated immunity. Neutralizing antibodies were first detected at day 7, reaching optimal titers at day 14. Complement fixing antibodies were detected from day 14 onward. Reinfection caused a very weak booster effect only on neutralizing antibody production. The sensitivity of the neutralization test could be enhanced up to sixfold by the addition of fresh guinea pig complement. It is concluded that cell-mediated immunity influences the early stage of infection with Aujeszky disease virus when humoral immunity is not yet demonstrable or yet rather low. Lymph nodes and spleen are apparently of special importance for the appearance of ADV-reactive lymphocytes.", "contents": "Cell-mediated immunity in Aujeszky disease virus infected pigs. I. Lymphocyte stimulation. The appearance of cell-mediated immunity was studied in Aujeszky diseased pigs with the aid of the in vitro stimulation of sensitized lymphocytes. The first cell-mediated immunity reaction of lymphocytes occurred 4 days after infection. From day 7 to 35, the latest day tested, the reactions were most marked with lymphocytes from lymph nodes and spleen, whereas blood and thymus lymphocytes reacted less frequently; bone marrow lymphocytes showed no response. Reinfection did not considerably enhance lymphocyte reactivity. Humoral immunity was demonstrated a few days later than cell-mediated immunity. Neutralizing antibodies were first detected at day 7, reaching optimal titers at day 14. Complement fixing antibodies were detected from day 14 onward. Reinfection caused a very weak booster effect only on neutralizing antibody production. The sensitivity of the neutralization test could be enhanced up to sixfold by the addition of fresh guinea pig complement. It is concluded that cell-mediated immunity influences the early stage of infection with Aujeszky disease virus when humoral immunity is not yet demonstrable or yet rather low. Lymph nodes and spleen are apparently of special importance for the appearance of ADV-reactive lymphocytes."} {"id": "PMID:176975", "title": "Enhanced SV 40-virus replication in chinese hamster kidney cells pretreated with 5-iodo-2'-deoxyuridine.", "content": "SV40 virion production was enhanced when semipermissive Chinese hamster kidney cells were treated with 5-iodo-2'-deoxyuridine (IUDR), prior to infection either with virus or viral-DNA. Pretreatment did not increase SV40 replication in fully permissive monkey kidney and nonpermissive Syrian hamster or mouse embryo cells.", "contents": "Enhanced SV 40-virus replication in chinese hamster kidney cells pretreated with 5-iodo-2'-deoxyuridine. SV40 virion production was enhanced when semipermissive Chinese hamster kidney cells were treated with 5-iodo-2'-deoxyuridine (IUDR), prior to infection either with virus or viral-DNA. Pretreatment did not increase SV40 replication in fully permissive monkey kidney and nonpermissive Syrian hamster or mouse embryo cells."} {"id": "PMID:176976", "title": "[Tissue nature of the lining of the lymph node sinuses].", "content": "The lymphatic nodes of intact albino rats were investigated electron microscopically. It was shown that the lymphatic sinuses were restricted by a layer of flattened cells; the basal membrane was absent. Certain distinctions in the structure of the cell lining sinuses and the reticular cells comprising the reticular base of the lymphoid tissue of the lymphatic node were found. The structure of the \"sinus network\" strands is shown. The structure of the cells of the sinuses lining is shown to be identical to the structure of cells of the vascular endothelium. It suggests the endothelial nature of the lining of the lymphatic node sinuses.", "contents": "[Tissue nature of the lining of the lymph node sinuses]. The lymphatic nodes of intact albino rats were investigated electron microscopically. It was shown that the lymphatic sinuses were restricted by a layer of flattened cells; the basal membrane was absent. Certain distinctions in the structure of the cell lining sinuses and the reticular cells comprising the reticular base of the lymphoid tissue of the lymphatic node were found. The structure of the \"sinus network\" strands is shown. The structure of the cells of the sinuses lining is shown to be identical to the structure of cells of the vascular endothelium. It suggests the endothelial nature of the lining of the lymphatic node sinuses."} {"id": "PMID:176977", "title": "[Lesions of the central nervous system in adenovirus infections].", "content": "The investigation of the central nervous system in generalized adenoviral infection in two children showed the presence in large nuclei of the nerve cells of hyperchromic inclusions containing the antigen of adenovirus. This testifies to the possibility of developing encephalites caused by respiratory viruses.", "contents": "[Lesions of the central nervous system in adenovirus infections]. The investigation of the central nervous system in generalized adenoviral infection in two children showed the presence in large nuclei of the nerve cells of hyperchromic inclusions containing the antigen of adenovirus. This testifies to the possibility of developing encephalites caused by respiratory viruses."} {"id": "PMID:176978", "title": "[A histochemical study of the effect of progesterone on the carbohydrate metabolism enzymes of different morphologic forms of endometrial cancer].", "content": "The histochemical method was used for determining glycogen, phosphorylase, glycogensynthetase, and glucose-6-phosphatase in order to evaluate the effect of progesterone on different morphological forms of cancer of the endometrium in man. On the basis of histochemical analysis of changes in the carbohydrate metabolism in 29 cases of cancer before and after treatment with progesterone a conclusion is drawn that sensitivity of tumours of the endometrium to hormonotherapy only partially depends upon the degree of their morphological differentiation.", "contents": "[A histochemical study of the effect of progesterone on the carbohydrate metabolism enzymes of different morphologic forms of endometrial cancer]. The histochemical method was used for determining glycogen, phosphorylase, glycogensynthetase, and glucose-6-phosphatase in order to evaluate the effect of progesterone on different morphological forms of cancer of the endometrium in man. On the basis of histochemical analysis of changes in the carbohydrate metabolism in 29 cases of cancer before and after treatment with progesterone a conclusion is drawn that sensitivity of tumours of the endometrium to hormonotherapy only partially depends upon the degree of their morphological differentiation."} {"id": "PMID:176979", "title": "[The condition of mitochondria in experimental viral carcinogenesis].", "content": "A parallel histoenzymatic and electron-microscopy study of the state of mitochondria in experimental viral cancerogenesis induced by adenovirus of monkeys SA7(C8) and virus of Rous sarcoma in soft tissues of hamster was carried out. It was shown that the earliest changes in the cell in the process of its tumorous transformation were those in mitochondria. The character of deposits of diformazin at an early stage of viral cancerogenesis corresponded to the trend to the linear arrangement of mitochondria and to initial phenomena of their swelling. Progressive swelling of mitochondria in the process of tumorous growth was established, which correlated with histochemically revealed changes in the relationships of a number of reduction-oxidation enzymes.", "contents": "[The condition of mitochondria in experimental viral carcinogenesis]. A parallel histoenzymatic and electron-microscopy study of the state of mitochondria in experimental viral cancerogenesis induced by adenovirus of monkeys SA7(C8) and virus of Rous sarcoma in soft tissues of hamster was carried out. It was shown that the earliest changes in the cell in the process of its tumorous transformation were those in mitochondria. The character of deposits of diformazin at an early stage of viral cancerogenesis corresponded to the trend to the linear arrangement of mitochondria and to initial phenomena of their swelling. Progressive swelling of mitochondria in the process of tumorous growth was established, which correlated with histochemically revealed changes in the relationships of a number of reduction-oxidation enzymes."} {"id": "PMID:176980", "title": "[Malignant glomus tumors of the stomach].", "content": "A total of 16 malignant glomic tumours of the stomach were studied. It is established that these tumours, as well as benign formations, have organoid structure, but differ from the latter by disorders of the tissue architectonics, polymorphism of cells of various degree, occasionally insignificantly manifested. The clinical course of the tumours not always corresponds to their histological structure--in mature microscopic structure they are sometimes characterised by local destructive growth and can give metastases. The authors propose to differentiate among malignant glomic tumours of the stomach the same variants of the morphological structure as in benign ones, i.e., myoid, angioleiomyomatous, angiopericytic, and paraganglioma-like. The authors assume that malignant glomic tumours of the stomach appear as a result of malignization of benign tumours.", "contents": "[Malignant glomus tumors of the stomach]. A total of 16 malignant glomic tumours of the stomach were studied. It is established that these tumours, as well as benign formations, have organoid structure, but differ from the latter by disorders of the tissue architectonics, polymorphism of cells of various degree, occasionally insignificantly manifested. The clinical course of the tumours not always corresponds to their histological structure--in mature microscopic structure they are sometimes characterised by local destructive growth and can give metastases. The authors propose to differentiate among malignant glomic tumours of the stomach the same variants of the morphological structure as in benign ones, i.e., myoid, angioleiomyomatous, angiopericytic, and paraganglioma-like. The authors assume that malignant glomic tumours of the stomach appear as a result of malignization of benign tumours."} {"id": "PMID:176981", "title": "[Morphofunctional state of pulmonary macrophages and their biological protection during phagocytosis of toxic elements].", "content": "Studies of a morphofunctional state of macrophages of the lungs of rats in phagocytosis of quartz (size of particles 1-2 mum) and against the background of prophylactic administration of polyvinylridine-N-oxyde (PVNO) were carried out using the method of quantitative cytochemistry (interference microscopy and cytometry) and electron-microscopy techniques (raster and transmissive). It was established that administration of PVNO led to intensification of the phagocytic activity of macrophages, increase in the content of RNA and dry weight (total proteins) therein, enlargement of the sizes of cells. The electron-microscopy investigation showed a good preservation of organelles of macrophages.", "contents": "[Morphofunctional state of pulmonary macrophages and their biological protection during phagocytosis of toxic elements]. Studies of a morphofunctional state of macrophages of the lungs of rats in phagocytosis of quartz (size of particles 1-2 mum) and against the background of prophylactic administration of polyvinylridine-N-oxyde (PVNO) were carried out using the method of quantitative cytochemistry (interference microscopy and cytometry) and electron-microscopy techniques (raster and transmissive). It was established that administration of PVNO led to intensification of the phagocytic activity of macrophages, increase in the content of RNA and dry weight (total proteins) therein, enlargement of the sizes of cells. The electron-microscopy investigation showed a good preservation of organelles of macrophages."} {"id": "PMID:176982", "title": "Neurologic manifestations of glomus tumors in the head and neck.", "content": "In 75 patients with glomus tumors in the head and neck region, 57 tumors arose from the jugular bulb region, 11 from the middle ear, and seven from the vagus nerve. Thirty-seven percent (28 patients) had cranial nerve paralysis, and 14.6% (11) had intracranial tumor extension. The jugular foramen syndrome was associated with a 50% (two of four patients) incidence, and hypoglossal nerve paralysis with a 75% (three of four) incidence of posterior fossa tumor invasion. Horner syndrome and labyrinthine destruction had a 50% (two of four) incidence of a middle cranial fossa tumor invasion. The incidence of central nervous system (CNS) invasion with cranial nerve paralysis (excluding the seventh nerve) was 52% (11 of 21). Otologic findings and seventh nerve paralysis did not correlate with CNS tumor extension.", "contents": "Neurologic manifestations of glomus tumors in the head and neck. In 75 patients with glomus tumors in the head and neck region, 57 tumors arose from the jugular bulb region, 11 from the middle ear, and seven from the vagus nerve. Thirty-seven percent (28 patients) had cranial nerve paralysis, and 14.6% (11) had intracranial tumor extension. The jugular foramen syndrome was associated with a 50% (two of four patients) incidence, and hypoglossal nerve paralysis with a 75% (three of four) incidence of posterior fossa tumor invasion. Horner syndrome and labyrinthine destruction had a 50% (two of four) incidence of a middle cranial fossa tumor invasion. The incidence of central nervous system (CNS) invasion with cranial nerve paralysis (excluding the seventh nerve) was 52% (11 of 21). Otologic findings and seventh nerve paralysis did not correlate with CNS tumor extension."} {"id": "PMID:176983", "title": "Palato-ocular synchrony during eyelid closure.", "content": "The effects of eyelid closure on oculomotor function was examined in 11 patients with palatal myoclonus. In eight patients, eyelid closure induced gross rhythmic vertical or almost oscillatory movements of the globes, which were synchronous with the rhythmic beat of the palatal myoclonus. The rhythmic vertical ocular movements induced by eyelid closure replaced calorically induced or spontaneous horizontal nystagmus present when the lids were open. Vertical ocular motions persisted during some stages of slow-wave sleep and reappeared during each stage of rapid eye movement. The physiologic basis of the palato-ocular synchrony may be similar to the eyelid closure, vertical eye movements, and palatal myoclonus that occurs in monkeys on stimulation of the central tegmental fasciculus.", "contents": "Palato-ocular synchrony during eyelid closure. The effects of eyelid closure on oculomotor function was examined in 11 patients with palatal myoclonus. In eight patients, eyelid closure induced gross rhythmic vertical or almost oscillatory movements of the globes, which were synchronous with the rhythmic beat of the palatal myoclonus. The rhythmic vertical ocular movements induced by eyelid closure replaced calorically induced or spontaneous horizontal nystagmus present when the lids were open. Vertical ocular motions persisted during some stages of slow-wave sleep and reappeared during each stage of rapid eye movement. The physiologic basis of the palato-ocular synchrony may be similar to the eyelid closure, vertical eye movements, and palatal myoclonus that occurs in monkeys on stimulation of the central tegmental fasciculus."} {"id": "PMID:176986", "title": "The oncogenic potential of some avian adenoviruses causing diseases in chickens.", "content": "The oncogenic potentials of three different strains of avian adenoviruses (the Tipton strain of the inclusion body hepatitis virus, the DPI-2, and the Indiana C viruses) were investigated in newborn hamsters. Animal inoculations were via two routes, subcutaneous and intracerebral. All three viruses proved nononcogenic for the hamsters observed over a period of 225 days. However, lesions of hepatitis similar to those of inclusion body hepatitis of chickens were seen in three hamsters inoculated with the DPI-2 virus.", "contents": "The oncogenic potential of some avian adenoviruses causing diseases in chickens. The oncogenic potentials of three different strains of avian adenoviruses (the Tipton strain of the inclusion body hepatitis virus, the DPI-2, and the Indiana C viruses) were investigated in newborn hamsters. Animal inoculations were via two routes, subcutaneous and intracerebral. All three viruses proved nononcogenic for the hamsters observed over a period of 225 days. However, lesions of hepatitis similar to those of inclusion body hepatitis of chickens were seen in three hamsters inoculated with the DPI-2 virus."} {"id": "PMID:176987", "title": "A lymphoproliferative disease in Japanese Quail.", "content": "A naturally occurring lymphoproliferative disease was found in 3 flocks of Japanese quail in Mexico. The tumorlike lesions were detected mainly in livers and spleens. Histopathology revealed a pleomorphic lymphoproliferative infiltration with dark-staining large cells, lymphocytes of different sizes, and reticulumlike cells. Marek's disease (MD) herpesvirus was not isolated from 74 quail tested, nor were antibodies to MD detected in 84 sera. Antibodies to reticuloendotheliosis (3/24) and avain leukosis virus subgroup A (2/24) were present. The possible etiology of this disease is discussed.", "contents": "A lymphoproliferative disease in Japanese Quail. A naturally occurring lymphoproliferative disease was found in 3 flocks of Japanese quail in Mexico. The tumorlike lesions were detected mainly in livers and spleens. Histopathology revealed a pleomorphic lymphoproliferative infiltration with dark-staining large cells, lymphocytes of different sizes, and reticulumlike cells. Marek's disease (MD) herpesvirus was not isolated from 74 quail tested, nor were antibodies to MD detected in 84 sera. Antibodies to reticuloendotheliosis (3/24) and avain leukosis virus subgroup A (2/24) were present. The possible etiology of this disease is discussed."} {"id": "PMID:176988", "title": "Identification of seven isolants of infectious bronchitis virus by interference with the B-1 isolant of Newcastle disease virus.", "content": "Seven isolants of infectious bronchitis virus (IBV) interfered with the development of hemagglutinins (HA) by the B-1 isolant of Newcaslte disease virus (NDV) in eggs previously inoculated with these IBV isolants. The I50 [defined as the minimum amount of IBV needed to produce, upon inoculation in embryonating chicken eggs (ECE), HA interference in 50% of these ECE reioculated 10 hr later with 10(2,41 EID50 (HA) of the B-1 strain of NDV] was less than 1 EID50. The interference was considered specific for IBV because if could be eliminated by addition of homologous anti-IBV serum. Furthermore, three other common poultry viruses (laryngotracheitis, fowlpox, and CELO viruses) did not interfere with NDV. In view of its sensitivity, specificity, and simplicity of performance, the IBV-NDV interference test appears to have considerable potential as a diagnostic test for IBV under field conditions.", "contents": "Identification of seven isolants of infectious bronchitis virus by interference with the B-1 isolant of Newcastle disease virus. Seven isolants of infectious bronchitis virus (IBV) interfered with the development of hemagglutinins (HA) by the B-1 isolant of Newcaslte disease virus (NDV) in eggs previously inoculated with these IBV isolants. The I50 [defined as the minimum amount of IBV needed to produce, upon inoculation in embryonating chicken eggs (ECE), HA interference in 50% of these ECE reioculated 10 hr later with 10(2,41 EID50 (HA) of the B-1 strain of NDV] was less than 1 EID50. The interference was considered specific for IBV because if could be eliminated by addition of homologous anti-IBV serum. Furthermore, three other common poultry viruses (laryngotracheitis, fowlpox, and CELO viruses) did not interfere with NDV. In view of its sensitivity, specificity, and simplicity of performance, the IBV-NDV interference test appears to have considerable potential as a diagnostic test for IBV under field conditions."} {"id": "PMID:176989", "title": "New strains of infectious bronchitis virus isolated in Maine.", "content": "Twelve IBV isolants from diseased chickens in Maine were studied by serum-neutralization tests in chicken tracheal culture. Six isolants were neutralized by Mass-type antisera. The serum-neutralizing characteristics of six other isolants from vaccine breaks differed from any of the standard IBV viruses and appear to comprise three new strains, Maine 209, 212,and 246. The data provide additional evidence that strains of IBV responsible for disease probably vary from region to region and that the strains present must be known for a regional vaccination program to be effective.", "contents": "New strains of infectious bronchitis virus isolated in Maine. Twelve IBV isolants from diseased chickens in Maine were studied by serum-neutralization tests in chicken tracheal culture. Six isolants were neutralized by Mass-type antisera. The serum-neutralizing characteristics of six other isolants from vaccine breaks differed from any of the standard IBV viruses and appear to comprise three new strains, Maine 209, 212,and 246. The data provide additional evidence that strains of IBV responsible for disease probably vary from region to region and that the strains present must be known for a regional vaccination program to be effective."} {"id": "PMID:176991", "title": "Immunity to infectious bronchitis virus from spray vaccination with derivatives of a Holland strain.", "content": "Study was made of the protection of chickens from spray vaccination with different modifications of a Holland (H) strain of infectious bronchitis virus (IBV). Noted in each trial were the virus-serum-neutralizing antibody titers induced and the virulence of the vaccine virus at different passage levels. Protection against respiratory signs was good from challenge with a homologous virus serotype as well as with 5 heterologous IBV isolates. This occurred from vaccinating day-old chicks possessing homologous IBV antibodies as well as vaccinating susceptible 4-week-old chickens. The tracheal virus shed-rate following challenge was considered low (20% or less) with 4 of the challenge viruses. The challenge virus shed-rate was somewhat higher from vaccination at one day old than from vaccination at 4 weeks; the virus-serum-neutralization titers were lower, or even insignificant, with early-age vaccination. The immunogenicity and virulence of the vaccine virus was apparently reduced in the higher embryo passages employed. None of the vaccine derivatives was considered virulent under these conditions.", "contents": "Immunity to infectious bronchitis virus from spray vaccination with derivatives of a Holland strain. Study was made of the protection of chickens from spray vaccination with different modifications of a Holland (H) strain of infectious bronchitis virus (IBV). Noted in each trial were the virus-serum-neutralizing antibody titers induced and the virulence of the vaccine virus at different passage levels. Protection against respiratory signs was good from challenge with a homologous virus serotype as well as with 5 heterologous IBV isolates. This occurred from vaccinating day-old chicks possessing homologous IBV antibodies as well as vaccinating susceptible 4-week-old chickens. The tracheal virus shed-rate following challenge was considered low (20% or less) with 4 of the challenge viruses. The challenge virus shed-rate was somewhat higher from vaccination at one day old than from vaccination at 4 weeks; the virus-serum-neutralization titers were lower, or even insignificant, with early-age vaccination. The immunogenicity and virulence of the vaccine virus was apparently reduced in the higher embryo passages employed. None of the vaccine derivatives was considered virulent under these conditions."} {"id": "PMID:176992", "title": "Isolation and identification of a turkey respiratory adenovirus.", "content": "A virus with physical and biological characteristics of an adenovirus was isolated from turkey poults with respiratory disease. The virus was ether-resistant and incorporated [3H] thymidine. Electron microscopy revealed virions of icosahedral configuration, approximately 78 nm in diameter, within the nuclei of infected cells. The virus produced cytopathology in turkey kidney cells, but did not produce observable disease when inoculated into commercial turkey poults or specific-pathogen-free embryonated chicken eggs. Virus-neutralization tests indicated widespread exposure to the virus in North Carolina turkey populations.", "contents": "Isolation and identification of a turkey respiratory adenovirus. A virus with physical and biological characteristics of an adenovirus was isolated from turkey poults with respiratory disease. The virus was ether-resistant and incorporated [3H] thymidine. Electron microscopy revealed virions of icosahedral configuration, approximately 78 nm in diameter, within the nuclei of infected cells. The virus produced cytopathology in turkey kidney cells, but did not produce observable disease when inoculated into commercial turkey poults or specific-pathogen-free embryonated chicken eggs. Virus-neutralization tests indicated widespread exposure to the virus in North Carolina turkey populations."} {"id": "PMID:176993", "title": "The influence of thymectomy on Rous sarcoma regression.", "content": "The incidence of regression of wing-web tumors induced by Rous sarcoma virus was shown to be dependent on the quantity of thymus tissue remaining after neonatal thymectomy in chickens of inbred line 6. Frequency of metastasis was associated negatively with the amount of thymus tissue present. Tumor regression and metastasis restriction both appeared dependent on the quantity of thymic tissue present.", "contents": "The influence of thymectomy on Rous sarcoma regression. The incidence of regression of wing-web tumors induced by Rous sarcoma virus was shown to be dependent on the quantity of thymus tissue remaining after neonatal thymectomy in chickens of inbred line 6. Frequency of metastasis was associated negatively with the amount of thymus tissue present. Tumor regression and metastasis restriction both appeared dependent on the quantity of thymic tissue present."} {"id": "PMID:176998", "title": "Expression of the human adenylate kinase isozymes, phosphopyruvate hydratase, 6-phosphogluconate dehydrogenase, and phosphoglucomutase-1 in man-rodent somatic cell hybrids.", "content": "The expression of the adenylate kinase isozymes and of phosphopyruvate hydratase was studied in man-mouse and man-hamster hybrid clones. Concordant segregation of the loci coding for AK-2 and PPH was observed in 54 of 55 primary hybrid clones, and these loci were demonstrated to be synthetic with the loci specifying PGM-1 and PGD. The pattern of expression of the four enzymes in discordant clone suggests the gene order 1pter-(PGD, PPH)-AK-2-PGM-1-centromere. In addition, AK-1 was found to be expressed independently of AK-2.", "contents": "Expression of the human adenylate kinase isozymes, phosphopyruvate hydratase, 6-phosphogluconate dehydrogenase, and phosphoglucomutase-1 in man-rodent somatic cell hybrids. The expression of the adenylate kinase isozymes and of phosphopyruvate hydratase was studied in man-mouse and man-hamster hybrid clones. Concordant segregation of the loci coding for AK-2 and PPH was observed in 54 of 55 primary hybrid clones, and these loci were demonstrated to be synthetic with the loci specifying PGM-1 and PGD. The pattern of expression of the four enzymes in discordant clone suggests the gene order 1pter-(PGD, PPH)-AK-2-PGM-1-centromere. In addition, AK-1 was found to be expressed independently of AK-2."} {"id": "PMID:176999", "title": "Resolution and functional characterization of two mitochondrial iron-sulphur centres of the 'high-potential iron-sulphur protein' type.", "content": "Two distinct iron-sulphur centres of the 'HiPIP' (high-potential iron-protein) type are distinguished in both pigeon heart and ox heart mitochondria. These two species, although both are paramagnetic in the oxidized state, exhibit signals which differ in their detailed line shape, field position, and temperature- and power-dependence. They also exhibit different thermodynamic and kinetic behaviour and are located on opposite sides of the mitochondrial coupling membrane. One of these centres corresponds to Centre S-3. The other 'HiPIP'-type centre is removed readily from the mitochondrial membrane and its physiological function is not known.", "contents": "Resolution and functional characterization of two mitochondrial iron-sulphur centres of the 'high-potential iron-sulphur protein' type. Two distinct iron-sulphur centres of the 'HiPIP' (high-potential iron-protein) type are distinguished in both pigeon heart and ox heart mitochondria. These two species, although both are paramagnetic in the oxidized state, exhibit signals which differ in their detailed line shape, field position, and temperature- and power-dependence. They also exhibit different thermodynamic and kinetic behaviour and are located on opposite sides of the mitochondrial coupling membrane. One of these centres corresponds to Centre S-3. The other 'HiPIP'-type centre is removed readily from the mitochondrial membrane and its physiological function is not known."} {"id": "PMID:177000", "title": "Effects of cholecalciferol on the translocation of calcium by non-everted chick ileum in vitro.", "content": "An apparatus is described that allows perfusion of a non-everted segment of intestine in vitro and the study of the accumulation of substances within the mucosal cells. The translocation of Ca(2+) by rachitic-chick ileum and the effect of pretreatment with cholecalciferol was investigated, with the following conclusions. (1) Entry of Ca(2+) across the microvilli into mucosal cells is by diffusion; it does not require metabolic energy or the presence of any other inorganic ions. (2) Pretreatment of the chick with cholecalciferol causes increased permeability of the microvillus to Ca(2+) in both directions (lumen to cell, cell to lumen). The increased transport brought about by cholecalciferol in vivo can be partially mimicked by sodium dodecyl sulphate added in vitro. (3) The sign and the magnitude of the electrical potential difference prevailing across the ileum does not influence Ca(2+) transport. (4) Exit of Ca(2+) from the mucosal cell is temperature-sensitive, requires metabolic energy and Na(+). (5) Pretreatment with cholecalciferol caused increased movement of Ca(2+) out of the cell across the basement membranes. This effect of cholecalciferol given in vivo could be markedly increased by the presence of dicyclohexylcarbodi-imide in the perfusion fluid. These observations suggested that cholecalciferol increased Ca(2+) entry (and exit) at the mucosal surface and also caused Ca(2+) to be more available to the pump at the serosal surface.", "contents": "Effects of cholecalciferol on the translocation of calcium by non-everted chick ileum in vitro. An apparatus is described that allows perfusion of a non-everted segment of intestine in vitro and the study of the accumulation of substances within the mucosal cells. The translocation of Ca(2+) by rachitic-chick ileum and the effect of pretreatment with cholecalciferol was investigated, with the following conclusions. (1) Entry of Ca(2+) across the microvilli into mucosal cells is by diffusion; it does not require metabolic energy or the presence of any other inorganic ions. (2) Pretreatment of the chick with cholecalciferol causes increased permeability of the microvillus to Ca(2+) in both directions (lumen to cell, cell to lumen). The increased transport brought about by cholecalciferol in vivo can be partially mimicked by sodium dodecyl sulphate added in vitro. (3) The sign and the magnitude of the electrical potential difference prevailing across the ileum does not influence Ca(2+) transport. (4) Exit of Ca(2+) from the mucosal cell is temperature-sensitive, requires metabolic energy and Na(+). (5) Pretreatment with cholecalciferol caused increased movement of Ca(2+) out of the cell across the basement membranes. This effect of cholecalciferol given in vivo could be markedly increased by the presence of dicyclohexylcarbodi-imide in the perfusion fluid. These observations suggested that cholecalciferol increased Ca(2+) entry (and exit) at the mucosal surface and also caused Ca(2+) to be more available to the pump at the serosal surface."} {"id": "PMID:177001", "title": "Phosphatidate phosphohydrolase and palmitoyl-coenzyme A hydrolase in cardiac subcellular fractions of hyperthyroid rabbits and cardiomyopathic hamsters.", "content": "Activities of phosphatidate phosphohydrolase and palmitoyl-CoA hydrolase were determined in cardiac subcellular fractions prepared from rabbits which has received tri-iodothyronine and from hamsters with hereditary cardiomyopathy (strain BIO 14.6). 1. Both mitochondrial and microsomal fractions of hyperthyroid rabbit hearts produced 4-5 times as much diacylglycerol 3-phosphate from glycerol 3-phosphate and palmitate as did those of euthyroid hearts. 2. Phosphatidate phosphohydrolase, measured with phosphatidate emulsion, was activated by 1mm-Mg(2+) in all but the mitochondrial fraction of euthyroid rabbit hearts. The activation was more pronounced in subcellular fractions isolated from hyperthyroid hearts, so that the measured activities were significantly increased above those of the controls. The highest activity was found in the microsomal and lysosomal fractions. 3. In the absence of Mg(2+) during incubation, the difference in phosphohydrolase activities between eu- and hyper-thyroid states was not significant. 4. The phosphohydrolase of subcellular fractions of control hamsters did not respond to addition of 0.5-8.0mm-Mg(2+). The enzyme from cardiomyopathic hearts was slightly inhibited by this bivalent cation and therefore significant increases in activity were observed only in the absence of Mg(2+) from the assay system. 5. The rate of reaction by soluble phosphatidate phosphohydrolase was similar regardless of the nature of the substrate. Both when microsomal-bound phosphatidate was used as the substrate and when phosphatidate suspension was used, the activity of soluble enzyme was lower than that of the microsomal and lysosomal enzymes measured with phosphatidate suspension; this was especially so when the assay was carried out in the absence of Mg(2+). Neither tri-iodothyronine nor cardiomyopathy influenced the soluble phosphohydrolase activity in the two species. 6. Neither tri-iodothyronine nor cardiomyopathy significantly changed palmitoyl-CoA hydrolase activities in subcellular fractions. 7. Microsomal diacylglycerol acyltransferase and myocardial triacylglycerol content were also unchanged in the hyperthyroid state.", "contents": "Phosphatidate phosphohydrolase and palmitoyl-coenzyme A hydrolase in cardiac subcellular fractions of hyperthyroid rabbits and cardiomyopathic hamsters. Activities of phosphatidate phosphohydrolase and palmitoyl-CoA hydrolase were determined in cardiac subcellular fractions prepared from rabbits which has received tri-iodothyronine and from hamsters with hereditary cardiomyopathy (strain BIO 14.6). 1. Both mitochondrial and microsomal fractions of hyperthyroid rabbit hearts produced 4-5 times as much diacylglycerol 3-phosphate from glycerol 3-phosphate and palmitate as did those of euthyroid hearts. 2. Phosphatidate phosphohydrolase, measured with phosphatidate emulsion, was activated by 1mm-Mg(2+) in all but the mitochondrial fraction of euthyroid rabbit hearts. The activation was more pronounced in subcellular fractions isolated from hyperthyroid hearts, so that the measured activities were significantly increased above those of the controls. The highest activity was found in the microsomal and lysosomal fractions. 3. In the absence of Mg(2+) during incubation, the difference in phosphohydrolase activities between eu- and hyper-thyroid states was not significant. 4. The phosphohydrolase of subcellular fractions of control hamsters did not respond to addition of 0.5-8.0mm-Mg(2+). The enzyme from cardiomyopathic hearts was slightly inhibited by this bivalent cation and therefore significant increases in activity were observed only in the absence of Mg(2+) from the assay system. 5. The rate of reaction by soluble phosphatidate phosphohydrolase was similar regardless of the nature of the substrate. Both when microsomal-bound phosphatidate was used as the substrate and when phosphatidate suspension was used, the activity of soluble enzyme was lower than that of the microsomal and lysosomal enzymes measured with phosphatidate suspension; this was especially so when the assay was carried out in the absence of Mg(2+). Neither tri-iodothyronine nor cardiomyopathy influenced the soluble phosphohydrolase activity in the two species. 6. Neither tri-iodothyronine nor cardiomyopathy significantly changed palmitoyl-CoA hydrolase activities in subcellular fractions. 7. Microsomal diacylglycerol acyltransferase and myocardial triacylglycerol content were also unchanged in the hyperthyroid state."} {"id": "PMID:177002", "title": "Regulation of mitochondrial protein turnover by thyroid hormone(s).", "content": "1. The effect of thyroidectomy on turnover rates of liver, kidney and brain mitochondrial proteins was examined. 2. In the euthyroid state, liver and kidney mitochondria show a synchronous turnover with all protein components showing more or less identical half-lives compared with the whole mitochondria. The brain mitochondrial proteins show asynchronous turnover, the soluble proteins having shorter half-lives. 3. Mitochondrial DNA (m-DNA) of liver and kidney has half-lives comparable with that of whole mitochondria from these tissues. 4. Thyroidectomy results in increased half-lives of liver and kidney mitochondria, with no apparent change in the half-life of brain mitochondria. 5. A detailed investigation of the turnover rates of several protein components revealed a significant decrease in the turnover rates of mitochondrial insoluble proteins from the three tissues under study. 6. The turnover rates of m-DNA of liver and kidney show a parallel decrease. 7. Thus it is apparent that thyroid hormone(s) may have a regulatory role in maintaining the synchrony of turnover of liver and kidney mitochondria in the euthyroid state. Turnover of brain mitochondria may perhaps be regulated by some other factor(s) in addition to thyroid hormone(s). 8. It seems likely that during mitochondrial turnover m-DNA and insoluble proteins may constitute a major unit. 9. The mitochondrial protein contents of the three tissues are not affected by thyroidectomy. 10. No correlation was seen between the turnover rate of mitochondria and cathepsin activity in any of the tissues under study in normal or thyroidectomized animals. 11. On the other hand, mitochondrial proteinase activity shows good correlation with the turnover rates of mitochondria in normal animals, and a parallel decrease in activity comparable with the decreased rates of turnover is observed after thyroidectomy. 12. It is concluded that mitochondrial proteinase activity may play a significant role in their protein turnover.", "contents": "Regulation of mitochondrial protein turnover by thyroid hormone(s). 1. The effect of thyroidectomy on turnover rates of liver, kidney and brain mitochondrial proteins was examined. 2. In the euthyroid state, liver and kidney mitochondria show a synchronous turnover with all protein components showing more or less identical half-lives compared with the whole mitochondria. The brain mitochondrial proteins show asynchronous turnover, the soluble proteins having shorter half-lives. 3. Mitochondrial DNA (m-DNA) of liver and kidney has half-lives comparable with that of whole mitochondria from these tissues. 4. Thyroidectomy results in increased half-lives of liver and kidney mitochondria, with no apparent change in the half-life of brain mitochondria. 5. A detailed investigation of the turnover rates of several protein components revealed a significant decrease in the turnover rates of mitochondrial insoluble proteins from the three tissues under study. 6. The turnover rates of m-DNA of liver and kidney show a parallel decrease. 7. Thus it is apparent that thyroid hormone(s) may have a regulatory role in maintaining the synchrony of turnover of liver and kidney mitochondria in the euthyroid state. Turnover of brain mitochondria may perhaps be regulated by some other factor(s) in addition to thyroid hormone(s). 8. It seems likely that during mitochondrial turnover m-DNA and insoluble proteins may constitute a major unit. 9. The mitochondrial protein contents of the three tissues are not affected by thyroidectomy. 10. No correlation was seen between the turnover rate of mitochondria and cathepsin activity in any of the tissues under study in normal or thyroidectomized animals. 11. On the other hand, mitochondrial proteinase activity shows good correlation with the turnover rates of mitochondria in normal animals, and a parallel decrease in activity comparable with the decreased rates of turnover is observed after thyroidectomy. 12. It is concluded that mitochondrial proteinase activity may play a significant role in their protein turnover."} {"id": "PMID:177003", "title": "Gluconeogenesis by isolated guinea-pig liver parenchymal cells.", "content": "1. Guinea-pig hepatocytes were prepared by collagenase digestion of the perfused liver. 2. The highest rates of gluconeogenesis were obtained from fructose, followed by pyruvate, xylitol and lactate, glycerol and propionate in that order. Maximum rates of gluconeogenesis were attained at 6-10mm substrate. 3. An initial 15-min lag period occurred during gluconeogenesis from lactate. This lag was abolished by preincubating the cells or by preincubation plus the addition of NH(4)Cl or lysine. 4. The lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were increased during the lag and adjusted to values favouring rapid gluconeogenesis from lactate after 15min. 5. The data suggest that the low glucose synthesis during the lag resulted from a limitation of the glutamate-aspartate shuttle and from the unusual redox state of the NAD(+) couple prevailing during this period. 6. At 0.1mm, amino-oxyacetate, a transaminase inhibitor, decreased gluconeogenesis from lactate by 80%, but had a negligible effect on glucose production from pyruvate. Gluconeogenesis from lactate was also inhibited (20%) by 10mm-dl-3-hydroxybutyrate.", "contents": "Gluconeogenesis by isolated guinea-pig liver parenchymal cells. 1. Guinea-pig hepatocytes were prepared by collagenase digestion of the perfused liver. 2. The highest rates of gluconeogenesis were obtained from fructose, followed by pyruvate, xylitol and lactate, glycerol and propionate in that order. Maximum rates of gluconeogenesis were attained at 6-10mm substrate. 3. An initial 15-min lag period occurred during gluconeogenesis from lactate. This lag was abolished by preincubating the cells or by preincubation plus the addition of NH(4)Cl or lysine. 4. The lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were increased during the lag and adjusted to values favouring rapid gluconeogenesis from lactate after 15min. 5. The data suggest that the low glucose synthesis during the lag resulted from a limitation of the glutamate-aspartate shuttle and from the unusual redox state of the NAD(+) couple prevailing during this period. 6. At 0.1mm, amino-oxyacetate, a transaminase inhibitor, decreased gluconeogenesis from lactate by 80%, but had a negligible effect on glucose production from pyruvate. Gluconeogenesis from lactate was also inhibited (20%) by 10mm-dl-3-hydroxybutyrate."} {"id": "PMID:177004", "title": "The release of adenosine 3':5'-cyclic monophosphate from the isolated perfused rat heart.", "content": "Although basal release of cyclic AMP from isolated perfused rat hearts was not measurable, isoprenaline induced substantial release of the nucleotide, suggesting that in vivo the myocardium can contribute to plasma cyclic AMP. Anoxia also increased the amount of cyclic AMP released, but insulin and nicotinate alone or in combination had no effect.", "contents": "The release of adenosine 3':5'-cyclic monophosphate from the isolated perfused rat heart. Although basal release of cyclic AMP from isolated perfused rat hearts was not measurable, isoprenaline induced substantial release of the nucleotide, suggesting that in vivo the myocardium can contribute to plasma cyclic AMP. Anoxia also increased the amount of cyclic AMP released, but insulin and nicotinate alone or in combination had no effect."} {"id": "PMID:177028", "title": "Analysis of metabolic changes in revertants of antibiotic-resistant micobacteria.", "content": "In the present report evaluation of the possible metabolic changes in partially revertants of M. tuberculosis var. hominis, reisolated from strains at high levels of drug-resistance after treatment with mutagenic agents, was reported. Based on the data presented here, it must be concluded that no significant biological and biochemical differences in mycobacterial cells revertant from high mutants mono-resistant to four aminoglycosides (Sm, Kana, Vio, Neo) and p-aminonasalicylic acid (PAS) are to be found.", "contents": "Analysis of metabolic changes in revertants of antibiotic-resistant micobacteria. In the present report evaluation of the possible metabolic changes in partially revertants of M. tuberculosis var. hominis, reisolated from strains at high levels of drug-resistance after treatment with mutagenic agents, was reported. Based on the data presented here, it must be concluded that no significant biological and biochemical differences in mycobacterial cells revertant from high mutants mono-resistant to four aminoglycosides (Sm, Kana, Vio, Neo) and p-aminonasalicylic acid (PAS) are to be found."} {"id": "PMID:177029", "title": "[Seroepidemiologic research on the antipoliomyelitic immunity in adult unvaccinated subjects].", "content": "The Authors carried out a serological research on the polimyelitis viruses in 727 adult subjects who had not been vaccinated orally. The results of the titration of the neutralizing antibodies showed that the situation of immunity with respect to poliomyelitis is still satisfactory. However, the difficulty of making an exact estimation of the duration of the state of immunity to poliomyelitis, and the persistent, though reduced, circulation of wild polioviruses are such that a continuous epidemiological control is advisable.", "contents": "[Seroepidemiologic research on the antipoliomyelitic immunity in adult unvaccinated subjects]. The Authors carried out a serological research on the polimyelitis viruses in 727 adult subjects who had not been vaccinated orally. The results of the titration of the neutralizing antibodies showed that the situation of immunity with respect to poliomyelitis is still satisfactory. However, the difficulty of making an exact estimation of the duration of the state of immunity to poliomyelitis, and the persistent, though reduced, circulation of wild polioviruses are such that a continuous epidemiological control is advisable."} {"id": "PMID:177027", "title": "[ADAM syndrome].", "content": "We present six cases of ADAM syndrome, that we have been studying at the Unit of Clinical Genetics of the Hospital Infantil de M\u00e9xico. We wish to stress how it is possible using medical photography to appreciate the different characteristics of ADAM syndrome: A-Amniotic, D-Deformation, A-Adhesions, M-Mutilation.", "contents": "[ADAM syndrome]. We present six cases of ADAM syndrome, that we have been studying at the Unit of Clinical Genetics of the Hospital Infantil de M\u00e9xico. We wish to stress how it is possible using medical photography to appreciate the different characteristics of ADAM syndrome: A-Amniotic, D-Deformation, A-Adhesions, M-Mutilation."} {"id": "PMID:177035", "title": "Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influenced of systemic and local administration.", "content": "Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants.", "contents": "Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influenced of systemic and local administration. Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants."} {"id": "PMID:177036", "title": "Treatment of transplanted rat tumours with double-stranded RNA(BRL 5907). II. Treatment of pleural and peritoneal growths.", "content": "Intrapleural growth of transplanted rat tumours was prevented or retarded by intrapleural administration of double-stranded RNA. A similar suppression of growth was achieved with peitoneal tumours by the intraperitoneal injection of the compound. These studies indicate the possible potential of this form of treatment of thoracic and peritoneal tumours for clinical application in the treatment of mesothelioma.", "contents": "Treatment of transplanted rat tumours with double-stranded RNA(BRL 5907). II. Treatment of pleural and peritoneal growths. Intrapleural growth of transplanted rat tumours was prevented or retarded by intrapleural administration of double-stranded RNA. A similar suppression of growth was achieved with peitoneal tumours by the intraperitoneal injection of the compound. These studies indicate the possible potential of this form of treatment of thoracic and peritoneal tumours for clinical application in the treatment of mesothelioma."} {"id": "PMID:177037", "title": "Studies on the relationship between concanavalin A and SV40-transformed human fibroblasts.", "content": "The extent of binding of 125I-Con A to the surface of SV40-transformed human fibroblasts and the degree of agglutination of the cells by the native lectin have been measured. In addition, trypsinized and succinylated Con A have been used to study the effects of the lectin upon certain cell growth parameters. Trypsinized Con A was found to alter the growth rate, the saturation density and the contact inhibition of the transformed cells, an effect not neutralized by alph-methyl-D-mannoside.", "contents": "Studies on the relationship between concanavalin A and SV40-transformed human fibroblasts. The extent of binding of 125I-Con A to the surface of SV40-transformed human fibroblasts and the degree of agglutination of the cells by the native lectin have been measured. In addition, trypsinized and succinylated Con A have been used to study the effects of the lectin upon certain cell growth parameters. Trypsinized Con A was found to alter the growth rate, the saturation density and the contact inhibition of the transformed cells, an effect not neutralized by alph-methyl-D-mannoside."} {"id": "PMID:177038", "title": "Recovery of herpes simiae (B virus) from both primary and latent infections in rhesus monkeys.", "content": "The suspected ability of herpes simiae (B virus) to persist in a latent form has been confirmed in rhesus monkeys. The virus was recovered from primary oral lesions of 2 young monkeys and again, 6 months after disappearance of symptoms, from cultures of Gasserian ganglia taken from the same individuals. B virus was identified by its effects in vivo and in vitro and in cross neutralization tests with antisera to reference B virus and herpes simplex virus. Tests showed that the same virus was present in oral lesions and in ganglia. The one-way immunological relationship between herpes simplex virus and B virus was clearly shown in results of cross neutralization tests.", "contents": "Recovery of herpes simiae (B virus) from both primary and latent infections in rhesus monkeys. The suspected ability of herpes simiae (B virus) to persist in a latent form has been confirmed in rhesus monkeys. The virus was recovered from primary oral lesions of 2 young monkeys and again, 6 months after disappearance of symptoms, from cultures of Gasserian ganglia taken from the same individuals. B virus was identified by its effects in vivo and in vitro and in cross neutralization tests with antisera to reference B virus and herpes simplex virus. Tests showed that the same virus was present in oral lesions and in ganglia. The one-way immunological relationship between herpes simplex virus and B virus was clearly shown in results of cross neutralization tests."} {"id": "PMID:177039", "title": "Latency of Herpes Simiae (B virus) in rabbits.", "content": "When small doses of herpes simplex virus (HSV) were given to rabbits a significant degree of protection was afforded against later infection with herpes simiae (B virus). Only 12/47 rabbits died within 3 weeks of receiving B virus dosages that would normally have proved lethal. B virus became latent in survivors and was recovered from brain and spinal cord suspensions from rabbits which died within 6 months and from dorsal root ganglia of rabbits which had survived for more than 2 years without overt signs of infection. A minority of the survivors tested also yielded HSV. Rabbits with latent B virus in the ganglia showed little or no detectable neutralizing antibody to B virus. The possibility is discussed that human populations having a high frequency occurrence of HSV antibody may include carriers of latent B virus.", "contents": "Latency of Herpes Simiae (B virus) in rabbits. When small doses of herpes simplex virus (HSV) were given to rabbits a significant degree of protection was afforded against later infection with herpes simiae (B virus). Only 12/47 rabbits died within 3 weeks of receiving B virus dosages that would normally have proved lethal. B virus became latent in survivors and was recovered from brain and spinal cord suspensions from rabbits which died within 6 months and from dorsal root ganglia of rabbits which had survived for more than 2 years without overt signs of infection. A minority of the survivors tested also yielded HSV. Rabbits with latent B virus in the ganglia showed little or no detectable neutralizing antibody to B virus. The possibility is discussed that human populations having a high frequency occurrence of HSV antibody may include carriers of latent B virus."} {"id": "PMID:177040", "title": "Ultrastructural changes in livers of tumour bearing rats.", "content": "An ultrastructural study of the livers of rats bearing transplanted mammary carcinomata from 4 to 12 weeks after transplantation revealed changes mainly in cytoplasmic structure of hepatocytes. The significant findings were pleomorphism of mitochondria, presence of large number of myelin figures, marked increase in microbodies, dilatation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, intracytoplasmic cholesterol clefts and absence of increase in lysosomes. These alterations have been compared with that of others who have used different animal model systems to study the effect of tumour in livers of host. Centrioles in K\u00fcpffer cells are described for the first time in this study.", "contents": "Ultrastructural changes in livers of tumour bearing rats. An ultrastructural study of the livers of rats bearing transplanted mammary carcinomata from 4 to 12 weeks after transplantation revealed changes mainly in cytoplasmic structure of hepatocytes. The significant findings were pleomorphism of mitochondria, presence of large number of myelin figures, marked increase in microbodies, dilatation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, intracytoplasmic cholesterol clefts and absence of increase in lysosomes. These alterations have been compared with that of others who have used different animal model systems to study the effect of tumour in livers of host. Centrioles in K\u00fcpffer cells are described for the first time in this study."} {"id": "PMID:177041", "title": "Effects of 8-substituted adenosine 3',5'-monophosphate derivatives on high Km phosphodiesterase activity.", "content": "Most of twenty-one 8-substitued adenosine 3',5'-monophosphate derivatives were found to inhibit competitively the hydrolysis of adenosine 3'5'-monophosphate by partially purified high Km (Michaelis-Menten constant) phosphodiesterase from hog brain cortex, which had one active site at high concentration of adenosine 3',5'-monophosphate (0.3 to 4.0 mM). The Ki value for the 8-substituted alkylaminoadenosine 3'5'-monophosphate derivative was found to decrease with increasing unbranched carbon chain of the substituent, and a minimum value was obtained in the case of 8-octylaminoadenosine 3',5'-monophosphate. The Ki value, however, increased gradually as the substituent of derivative became longer than that of 8-octylminoadenosine 3'5'-monophosphate. The similar phenomenon was observed in the 8-substituted alkylthioadenosine 3',5'-monophosphate. The standard affinity for adenosine 3,5'-monophosphate of the high Km phosphodiesterase was 5.0 kcal/mol, which was calculated from Km. The standard affinity for 8-hexylthioadenosine 3',5'-monophosphate, which inhibited most strongly the enzyme activity, was 7.2 kcal/mol. The difference (2.2 kcal/736) between the standard affinity for adenosine 3',5'-monphosphate and that for 8-hexylthioadenosine 3',5'-monophosphate seems to be based on the partial affinity for the substituent (hexylthio group) of the active site on the enzyme or its neighborhood. A characteristic similar interrelation between substituent length of derivatives and their inhibitory effect on the enzyme activity was observed similarly in two different series of derivatives, 8-substituted alkylaminoadenosine 3',5'-monophosphate and alkylthioadenosine 3',5'-monophosphate. The results may indicate the characteristic structure of the active site of the enzyme or its neighborhood.", "contents": "Effects of 8-substituted adenosine 3',5'-monophosphate derivatives on high Km phosphodiesterase activity. Most of twenty-one 8-substitued adenosine 3',5'-monophosphate derivatives were found to inhibit competitively the hydrolysis of adenosine 3'5'-monophosphate by partially purified high Km (Michaelis-Menten constant) phosphodiesterase from hog brain cortex, which had one active site at high concentration of adenosine 3',5'-monophosphate (0.3 to 4.0 mM). The Ki value for the 8-substituted alkylaminoadenosine 3'5'-monophosphate derivative was found to decrease with increasing unbranched carbon chain of the substituent, and a minimum value was obtained in the case of 8-octylaminoadenosine 3',5'-monophosphate. The Ki value, however, increased gradually as the substituent of derivative became longer than that of 8-octylminoadenosine 3'5'-monophosphate. The similar phenomenon was observed in the 8-substituted alkylthioadenosine 3',5'-monophosphate. The standard affinity for adenosine 3,5'-monophosphate of the high Km phosphodiesterase was 5.0 kcal/mol, which was calculated from Km. The standard affinity for 8-hexylthioadenosine 3',5'-monophosphate, which inhibited most strongly the enzyme activity, was 7.2 kcal/mol. The difference (2.2 kcal/736) between the standard affinity for adenosine 3',5'-monphosphate and that for 8-hexylthioadenosine 3',5'-monophosphate seems to be based on the partial affinity for the substituent (hexylthio group) of the active site on the enzyme or its neighborhood. A characteristic similar interrelation between substituent length of derivatives and their inhibitory effect on the enzyme activity was observed similarly in two different series of derivatives, 8-substituted alkylaminoadenosine 3',5'-monophosphate and alkylthioadenosine 3',5'-monophosphate. The results may indicate the characteristic structure of the active site of the enzyme or its neighborhood."} {"id": "PMID:177042", "title": "Molecular forms of acetylcholinesterase from Torpedo californica: their relationship to synaptic membranes.", "content": "The 16S and 8S forms of acetylcholinesterase (AchE), which are composed of an elongated tail structure in addition to the more globular catalytic subunits, were extracted and purified from membranes from Torpedo californica electric organs. Their subunit compositions and quaternary structures were compared with 11S lytic enzyme which is derived from collagenase or trypsin treatment of the membranes and devoid of the tail unit. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence of reducing agent, appreciable populations of monomeric through tetrameric species are observed for the 11S form. Under the same conditions, the 16S form yields only monomer and dimer in addition to a higher molecular weight species. If complete reduction is effected, only the 80,000 molecular weight monomer is dominant for both the 11S and 16S forms. Cross-linking of the 11S form by dimethyl suberimidate followed by reduction yields monomer through tetramer in descending frequency, while the 16S form again shows a high molecular weight species. A comparison of the composition of the 11S and 16S forms reveals that the latter has an increased glycine content, and 1.1 and 0.3 mol % hydroxyproline and hydroxylysine, respectively. Collagenases that have been purified to homogencity and are devoid of amidase and caseinolytic activity, but active against native collagen, will convert 16S acetylcholinesterase to the 11S form. Thus, composition and substrate behavior of the 16S enzyme are indicative of the tail unit containing a collagen-like sequence. A membrane fraction enriched in acetylcholinesterase and components of basement membrane can be separated from the major portion of the membrane protein. The 16S but not the 11S form reassociates selectively with this membrane fraction. These findings reveal distinct similarities between the tail unit of acetylcholinesterase and basement membrane components and suggest a primary association of AchE with the basement membrane.", "contents": "Molecular forms of acetylcholinesterase from Torpedo californica: their relationship to synaptic membranes. The 16S and 8S forms of acetylcholinesterase (AchE), which are composed of an elongated tail structure in addition to the more globular catalytic subunits, were extracted and purified from membranes from Torpedo californica electric organs. Their subunit compositions and quaternary structures were compared with 11S lytic enzyme which is derived from collagenase or trypsin treatment of the membranes and devoid of the tail unit. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence of reducing agent, appreciable populations of monomeric through tetrameric species are observed for the 11S form. Under the same conditions, the 16S form yields only monomer and dimer in addition to a higher molecular weight species. If complete reduction is effected, only the 80,000 molecular weight monomer is dominant for both the 11S and 16S forms. Cross-linking of the 11S form by dimethyl suberimidate followed by reduction yields monomer through tetramer in descending frequency, while the 16S form again shows a high molecular weight species. A comparison of the composition of the 11S and 16S forms reveals that the latter has an increased glycine content, and 1.1 and 0.3 mol % hydroxyproline and hydroxylysine, respectively. Collagenases that have been purified to homogencity and are devoid of amidase and caseinolytic activity, but active against native collagen, will convert 16S acetylcholinesterase to the 11S form. Thus, composition and substrate behavior of the 16S enzyme are indicative of the tail unit containing a collagen-like sequence. A membrane fraction enriched in acetylcholinesterase and components of basement membrane can be separated from the major portion of the membrane protein. The 16S but not the 11S form reassociates selectively with this membrane fraction. These findings reveal distinct similarities between the tail unit of acetylcholinesterase and basement membrane components and suggest a primary association of AchE with the basement membrane."} {"id": "PMID:177043", "title": "The monosaccharide composition and sequence of the carbohydrate moiety of human serum low density lipoproteins.", "content": "Human serum low density lipoprotein (d = 1.027-1.045) was delipidated with organic solvents and the apoprotein digested with thermolysin. The digest was fractionated by gel filtration and DEAE-cellulose chromatography. Two glycopeptides were obtained. One of the glycopeptides (GP-I) contained 2 residues of N-acetylglucosamine and 6 residues of mannose per mole of the glycopeptide, while the other contained 2 sialic acid, 5 mannose, 2 galactose, and 3 N-acetylglucosamine residues per mole of glycopeptide. The results of sequential enzymatic digestion with purified glycosidases, periodate oxidation, and partial acid hydrolysis lead us to propose the following sturctures for the two glycopeptides: (see article). These glycopeptides represent at least 50% of the carbohydrate moiety of LDL.", "contents": "The monosaccharide composition and sequence of the carbohydrate moiety of human serum low density lipoproteins. Human serum low density lipoprotein (d = 1.027-1.045) was delipidated with organic solvents and the apoprotein digested with thermolysin. The digest was fractionated by gel filtration and DEAE-cellulose chromatography. Two glycopeptides were obtained. One of the glycopeptides (GP-I) contained 2 residues of N-acetylglucosamine and 6 residues of mannose per mole of the glycopeptide, while the other contained 2 sialic acid, 5 mannose, 2 galactose, and 3 N-acetylglucosamine residues per mole of glycopeptide. The results of sequential enzymatic digestion with purified glycosidases, periodate oxidation, and partial acid hydrolysis lead us to propose the following sturctures for the two glycopeptides: (see article). These glycopeptides represent at least 50% of the carbohydrate moiety of LDL."} {"id": "PMID:177044", "title": "Inactivation and reactivation of mitochondrial respiration by charged detergents.", "content": "Respiration of submitochondrial preparations can be inhibited by the cationic detergent cetyl trimethyl ammonium bromide and the anionic detergent sodium dodecyl sulfate in the range of 0.3-2 mumol of detergent per mg of mitochondrial membrane protein depending on the substrate and detergent used. This inhibition can be rapidly reversed by neutralizing a given detergent by the detergent of the opposite charge. At higher levels of the inhibiting detergent, no such reactivation was observed. Spin labeling assays of membrane structure were used to correlate structural effects with the loss and recovery of respiratory functions. Because the detergents progressively disrupt membrane structure, mitochondrial were cross-linked with bifunctional imidoesters to an extent that osmotic properties and detergent lysis were gone, but respiration remained. Such fixed respiring mitochondria also show inhibition reactivation phenomena.", "contents": "Inactivation and reactivation of mitochondrial respiration by charged detergents. Respiration of submitochondrial preparations can be inhibited by the cationic detergent cetyl trimethyl ammonium bromide and the anionic detergent sodium dodecyl sulfate in the range of 0.3-2 mumol of detergent per mg of mitochondrial membrane protein depending on the substrate and detergent used. This inhibition can be rapidly reversed by neutralizing a given detergent by the detergent of the opposite charge. At higher levels of the inhibiting detergent, no such reactivation was observed. Spin labeling assays of membrane structure were used to correlate structural effects with the loss and recovery of respiratory functions. Because the detergents progressively disrupt membrane structure, mitochondrial were cross-linked with bifunctional imidoesters to an extent that osmotic properties and detergent lysis were gone, but respiration remained. Such fixed respiring mitochondria also show inhibition reactivation phenomena."} {"id": "PMID:177045", "title": "Energy transduction in photosynthetic bacteria. X. Composition and function of the branched oxidase system in wild type and respiration deficient mutants of Rhodopseudomonas capsulata.", "content": "The respiratory chain of Rhodopseudomonas capsulata, strain St. Louis and of two respiration deficient mutants (M6 and M7) has been investigated by examining the redox and spectral characteristics of the cytochromes and their response to substrates and to specific respiratory inhibitors. Since the specific lesions of M6 and M7 have been localized on two different branches of the multiple oxidase system of the wild type strain, the capability for aerobic growth of these mutants can be considered as a proof of the physiological significance of both branched systems \"in vivo\". Using M6 and M7 mutants the response of the branched chain to respiratory inhibitors could be established. Cytochrome oxidase activity, a specific function of an high potential cytochrome b (E'0 = +413 mV) is sensitive to low concentrations of KCN (5-10(-5) M); CO is a specific inhibitor of an alternative oxidase, which is also inhibited by high concentrations of KCN (10(-3) M). Antimycin A inhibits preferentially the branch of the chain affected by low concentrations of cyanide. Redox titrations and spectral data indicate the presence in the membrane of three cytochromes of b type (E'0 = +413, +260, +47 vM) and two cytochromes of c type (E'0 = +342, +94 mV). A clear indication of the involvement in respiration of cytochrome b413, cytochrome c342 and cytochrome b47 has been obtained. Only 50% of the dithionite reducible cytochrome b can be reduced by respiratory substrates also in the presence of high concentrations of KCN or in anaerobiosis. The presence and function of quinones in the respiratory electron transport system has been clearly demonstrated. Quinones, which are reducible by NADH and succinate to about the same extent can be reoxidized through both branches of the respiratory chain, as shown by the response of their redox state to KCN. The possible site of the branching of the electron transport chain has been investigated comparing the per cent level of reduction of quinones and of cytochromes b and c as a function of KCN concentrations in membranes from wild type and M6 mutants cells. The site of the branching has been localized at the level of quinones-cytochrome b47. A tentative scheme of the respiratory chains operating in Rhodopseudomonas capsulata, St. Louis and in the two respiration deficient mutants, M6 and M7 is presented.", "contents": "Energy transduction in photosynthetic bacteria. X. Composition and function of the branched oxidase system in wild type and respiration deficient mutants of Rhodopseudomonas capsulata. The respiratory chain of Rhodopseudomonas capsulata, strain St. Louis and of two respiration deficient mutants (M6 and M7) has been investigated by examining the redox and spectral characteristics of the cytochromes and their response to substrates and to specific respiratory inhibitors. Since the specific lesions of M6 and M7 have been localized on two different branches of the multiple oxidase system of the wild type strain, the capability for aerobic growth of these mutants can be considered as a proof of the physiological significance of both branched systems \"in vivo\". Using M6 and M7 mutants the response of the branched chain to respiratory inhibitors could be established. Cytochrome oxidase activity, a specific function of an high potential cytochrome b (E'0 = +413 mV) is sensitive to low concentrations of KCN (5-10(-5) M); CO is a specific inhibitor of an alternative oxidase, which is also inhibited by high concentrations of KCN (10(-3) M). Antimycin A inhibits preferentially the branch of the chain affected by low concentrations of cyanide. Redox titrations and spectral data indicate the presence in the membrane of three cytochromes of b type (E'0 = +413, +260, +47 vM) and two cytochromes of c type (E'0 = +342, +94 mV). A clear indication of the involvement in respiration of cytochrome b413, cytochrome c342 and cytochrome b47 has been obtained. Only 50% of the dithionite reducible cytochrome b can be reduced by respiratory substrates also in the presence of high concentrations of KCN or in anaerobiosis. The presence and function of quinones in the respiratory electron transport system has been clearly demonstrated. Quinones, which are reducible by NADH and succinate to about the same extent can be reoxidized through both branches of the respiratory chain, as shown by the response of their redox state to KCN. The possible site of the branching of the electron transport chain has been investigated comparing the per cent level of reduction of quinones and of cytochromes b and c as a function of KCN concentrations in membranes from wild type and M6 mutants cells. The site of the branching has been localized at the level of quinones-cytochrome b47. A tentative scheme of the respiratory chains operating in Rhodopseudomonas capsulata, St. Louis and in the two respiration deficient mutants, M6 and M7 is presented."} {"id": "PMID:177046", "title": "The branched respiratory system of photosynthetically grown Rhodopseudomonas capsulata.", "content": "Various respiratory electron transport activities of Rhodopseudomonas capsulata were studied in membrane fragments prepared from photosynthetically grown cells of a parental strain and two terminal oxidase-defective mutant strains. The NADH and succinate oxidase activities of the mutant having a functional N,N,N1,N1-tetramethyl-p-phenylenediamine oxidase, M6, were consideraly more sensitive to inhibition by either antimycin A or cyanide than the corresponding activities of the mutant lacking a functional N,N,N1,N1-tetramethyl-p-phenylenediamine oxidase, M7. The parental strain, Z-1, but not the mutants, showed biphasic inhibitory responses of NADH and succinate oxidase activities with either antimycin A or cyanide. In certain reactions no differences in inhibitor susceptibility were found among the strains tested, implying that the pathways involved were unaffected in the mutants. In this category were the actions of rotenone on NADH oxidase, antimycin A on cytochrome c reductase and, in M6 and Z-1, cyanide on N,N,N'N'-tetramethyl-p-phenylenediamine oxidase. These results suggest that the respiratory chain of the parental strain branches at the ubiquinone-cytochrome b region into two pathways, each branch goes to a distinct terminal oxidase, and either may be blocked independently by genetic mutation.", "contents": "The branched respiratory system of photosynthetically grown Rhodopseudomonas capsulata. Various respiratory electron transport activities of Rhodopseudomonas capsulata were studied in membrane fragments prepared from photosynthetically grown cells of a parental strain and two terminal oxidase-defective mutant strains. The NADH and succinate oxidase activities of the mutant having a functional N,N,N1,N1-tetramethyl-p-phenylenediamine oxidase, M6, were consideraly more sensitive to inhibition by either antimycin A or cyanide than the corresponding activities of the mutant lacking a functional N,N,N1,N1-tetramethyl-p-phenylenediamine oxidase, M7. The parental strain, Z-1, but not the mutants, showed biphasic inhibitory responses of NADH and succinate oxidase activities with either antimycin A or cyanide. In certain reactions no differences in inhibitor susceptibility were found among the strains tested, implying that the pathways involved were unaffected in the mutants. In this category were the actions of rotenone on NADH oxidase, antimycin A on cytochrome c reductase and, in M6 and Z-1, cyanide on N,N,N'N'-tetramethyl-p-phenylenediamine oxidase. These results suggest that the respiratory chain of the parental strain branches at the ubiquinone-cytochrome b region into two pathways, each branch goes to a distinct terminal oxidase, and either may be blocked independently by genetic mutation."} {"id": "PMID:177047", "title": "A flash photolysis ESR study of photosystem II signal IIvf, the physiological donor to P-680+.", "content": "In flash-illuminated, oxygen-evolving spinach chloroplasts and green algae, a free radical transient has been observed with spectral parameters similar to those of Signal II (g approximately 2.0045, deltaHpp approximately 19G). However, in contrast with ESR Signal II, the transient radical does not readily saturate even at microwave power levels of 200 mW. This species is formed most efficiently with \"red\" illumination (lambda less than 680 nm) and occurs stoichiometrically in a 1:1 ratio with P-700+. The Photosystem II transient is formed in less than 100 mus and decays via first-order kinetics with a halftime of 400-900 mus. Additionally, the t1/2 for radical decay is temperature independent between 20 and 4 degrees C; however, below 4 degrees C the transient signal exhibits Arrhenius behavior with an activation energy of approx. 10 kcal-mol-1. Inhibition of electron transport through Photosystem II by o-phenanthroline, 3-(3,4-dichlorophenyl)-1,1-dimethylurea or reduced 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone suppresses the formation of the light-induced transient. At low concentrations (0.2 mM), 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone partially inhibits the free radical formation, however, the decay kinetics are unaltered. High concentrations of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (1-5 mM) restore both the transient signal and electron flow through Photosystem II. These findings suggest that this \"quinoidal\" type ESR transient functions as the physiological donor to the oxidized reaction center chlorophyll, P-680+.", "contents": "A flash photolysis ESR study of photosystem II signal IIvf, the physiological donor to P-680+. In flash-illuminated, oxygen-evolving spinach chloroplasts and green algae, a free radical transient has been observed with spectral parameters similar to those of Signal II (g approximately 2.0045, deltaHpp approximately 19G). However, in contrast with ESR Signal II, the transient radical does not readily saturate even at microwave power levels of 200 mW. This species is formed most efficiently with \"red\" illumination (lambda less than 680 nm) and occurs stoichiometrically in a 1:1 ratio with P-700+. The Photosystem II transient is formed in less than 100 mus and decays via first-order kinetics with a halftime of 400-900 mus. Additionally, the t1/2 for radical decay is temperature independent between 20 and 4 degrees C; however, below 4 degrees C the transient signal exhibits Arrhenius behavior with an activation energy of approx. 10 kcal-mol-1. Inhibition of electron transport through Photosystem II by o-phenanthroline, 3-(3,4-dichlorophenyl)-1,1-dimethylurea or reduced 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone suppresses the formation of the light-induced transient. At low concentrations (0.2 mM), 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone partially inhibits the free radical formation, however, the decay kinetics are unaltered. High concentrations of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (1-5 mM) restore both the transient signal and electron flow through Photosystem II. These findings suggest that this \"quinoidal\" type ESR transient functions as the physiological donor to the oxidized reaction center chlorophyll, P-680+."} {"id": "PMID:177049", "title": "Zero field resonance and spin alignment of the triplet state of chloroplasts at 2 degrees K.", "content": "Microwave induced transitions in zero magnetic field have been observed in the photoinduced triplet of chloroplasts treated with dithionite by monitoring changes in the intensity of the 735 nm fluorescence band at 2 degrees K. Similar results were obtained with chloroplasts treated with hydroxylamine plus 3-(3,4-dichlorophenyl)-1,1-dimethylurea and preillumination. The zero field parameters are D = 0.02794 +/- 0.00007 cm-1, E = 0.00382 +/- 0.00007 cm-1, i.e. equal to those of monomeric chlorophyll a to within the experimental error. The photoinduced triplet appears to be linked to Photosystem II. This indicates that the low temperatures 735 nm fluorescence band of chloroplasts is at least partly due to Photosystem II.", "contents": "Zero field resonance and spin alignment of the triplet state of chloroplasts at 2 degrees K. Microwave induced transitions in zero magnetic field have been observed in the photoinduced triplet of chloroplasts treated with dithionite by monitoring changes in the intensity of the 735 nm fluorescence band at 2 degrees K. Similar results were obtained with chloroplasts treated with hydroxylamine plus 3-(3,4-dichlorophenyl)-1,1-dimethylurea and preillumination. The zero field parameters are D = 0.02794 +/- 0.00007 cm-1, E = 0.00382 +/- 0.00007 cm-1, i.e. equal to those of monomeric chlorophyll a to within the experimental error. The photoinduced triplet appears to be linked to Photosystem II. This indicates that the low temperatures 735 nm fluorescence band of chloroplasts is at least partly due to Photosystem II."} {"id": "PMID:177050", "title": "Uptake and degradation of low density lipoprotein by swine arterial smoot muscle cells with inhibition of cholesterol biosynthesis.", "content": "We have previously proposed on the basis of studies in hepatectomized animals that low density lipoproteins are degraded at a significant rate by peripheral tissues. To test the capacity of one peripheral cell type to catabolize low density lipoprotein, cultures of swine aortic smooth muscle cells were incubated with homologous 125I-labeled low density lipoprotein and uptake and degradation measured. Degradation of 125I-labeled low density lipoprotein to products soluble in trichloroacetic acid showed an initial lag period of 1--2 h after which the rate increased and remained linear for the following 15 h. Rates of degradation increased sharply with low density lipoprotein concentration over the lower range (from 0--25 mug protein/ml) and then more slowly up to the highest concentration tested, 300 mug protein/ml. Even at very low concentrations, 1 mug low density lipoprotein protein/ml (less than 10% of the plasma low density lipoprotein concentration), the in vitro degradation rate (per kg of smooth muscle cells) exceeded the in vivo degradation rate (per kg of total body weight). To the extent that smooth muscle cells are representative of other peripheral cells, the results support the proposal that peripheral degradation of low density lipoprotein apoprotein may be quantitatively important. The rate of incorporation of labeled acetate into sterols was suppressed in cells incubated with whole serum, low density and very low density lipoproteins, or suspensions of free cholesterol. In this respect, the results were similar to those observed in human skin fibroblasts studied concurrently. However, high density lipoprotein inhibited sterol synthesis by about 25% in swine smooth muscle cells while it had no effect in human skin fibroblasts.", "contents": "Uptake and degradation of low density lipoprotein by swine arterial smoot muscle cells with inhibition of cholesterol biosynthesis. We have previously proposed on the basis of studies in hepatectomized animals that low density lipoproteins are degraded at a significant rate by peripheral tissues. To test the capacity of one peripheral cell type to catabolize low density lipoprotein, cultures of swine aortic smooth muscle cells were incubated with homologous 125I-labeled low density lipoprotein and uptake and degradation measured. Degradation of 125I-labeled low density lipoprotein to products soluble in trichloroacetic acid showed an initial lag period of 1--2 h after which the rate increased and remained linear for the following 15 h. Rates of degradation increased sharply with low density lipoprotein concentration over the lower range (from 0--25 mug protein/ml) and then more slowly up to the highest concentration tested, 300 mug protein/ml. Even at very low concentrations, 1 mug low density lipoprotein protein/ml (less than 10% of the plasma low density lipoprotein concentration), the in vitro degradation rate (per kg of smooth muscle cells) exceeded the in vivo degradation rate (per kg of total body weight). To the extent that smooth muscle cells are representative of other peripheral cells, the results support the proposal that peripheral degradation of low density lipoprotein apoprotein may be quantitatively important. The rate of incorporation of labeled acetate into sterols was suppressed in cells incubated with whole serum, low density and very low density lipoproteins, or suspensions of free cholesterol. In this respect, the results were similar to those observed in human skin fibroblasts studied concurrently. However, high density lipoprotein inhibited sterol synthesis by about 25% in swine smooth muscle cells while it had no effect in human skin fibroblasts."} {"id": "PMID:177051", "title": "The effect of hypoxia on uptake and degradation of low density lipoproteins by cultured human arterial smooth muscle cells.", "content": "Atheroma have been produced in experimental animal by systemic hypoxia. This study assessed the effects of hypoxia on binding, uptake and degradation of human low density lipoprotein (LDL) by human arterial smooth muscle cells, the cell involved in atherogenesis. The LDL content of the smooth muscle cell grown in the usual conditions (95% air [20% O2], 5% CO2) increased with the incubation time of LDL in the medium (7.5 mug protein/ml of medium); the trypsin releasable LDL \"binding\" reached a plateau by 24 h (2.2 +/- 1.3 [x +/- S.D.]) ng/mug LDL protein added per 10(6) cells whereas the LDL in the cell after trypsinization (\"net uptake\") continued to increase up to 48 h (6.5 +/- 4.6 ng/mug LDL protein added per 10(6) cells at 48 h). LDL protein degradation increases rapidly between 7 and 48 h (10.4 ng/mug LDL protein added per 10(6) cells at 24 h) after an initial delay of approximately 7 h. Smooth muscle cells grown under hypoxic conditions (5%02) had similar LDL \"binding \" but showed increased \"net uptake\" (10.7 +/- 4.8 ng/mug LDL protein added per 10(6) cells) and a 36 +/- 13% decrease in degradation (p less than 0.05; n =8). The impaired degradation of lipoprotein by smooth muscle cells may, in part, explain the role of hypoxia in atherogenesis.", "contents": "The effect of hypoxia on uptake and degradation of low density lipoproteins by cultured human arterial smooth muscle cells. Atheroma have been produced in experimental animal by systemic hypoxia. This study assessed the effects of hypoxia on binding, uptake and degradation of human low density lipoprotein (LDL) by human arterial smooth muscle cells, the cell involved in atherogenesis. The LDL content of the smooth muscle cell grown in the usual conditions (95% air [20% O2], 5% CO2) increased with the incubation time of LDL in the medium (7.5 mug protein/ml of medium); the trypsin releasable LDL \"binding\" reached a plateau by 24 h (2.2 +/- 1.3 [x +/- S.D.]) ng/mug LDL protein added per 10(6) cells whereas the LDL in the cell after trypsinization (\"net uptake\") continued to increase up to 48 h (6.5 +/- 4.6 ng/mug LDL protein added per 10(6) cells at 48 h). LDL protein degradation increases rapidly between 7 and 48 h (10.4 ng/mug LDL protein added per 10(6) cells at 24 h) after an initial delay of approximately 7 h. Smooth muscle cells grown under hypoxic conditions (5%02) had similar LDL \"binding \" but showed increased \"net uptake\" (10.7 +/- 4.8 ng/mug LDL protein added per 10(6) cells) and a 36 +/- 13% decrease in degradation (p less than 0.05; n =8). The impaired degradation of lipoprotein by smooth muscle cells may, in part, explain the role of hypoxia in atherogenesis."} {"id": "PMID:177052", "title": "The content of prostaglandin E and prostaglandin F2alpha in the exudate of carrageenin granuloma of rats.", "content": "1. Granuloma was made by the subcutaneous injection of 2% carrageenin solution on the dorsum of male rats. Eight, 16, 24 and 72 h after the injection. the exudate from each rat granuloma was withdrawn and extracted for rpstaglandins. 2. Extracted prostaglandins were separated prostaglandin E and prostaglandin F group by silicic acid mini-column chromatography. Then the amount of prostaglandin E and prostaglandin F2alpha were determined by the radioimmunoassay method. 3. The levels of prostaglandin E in the granuloma exudates were 4.6 ng/ml at 8 h after the carrageenin injection, then decreased 3.6 ng/ml and to 1.1 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the injection, prostaglandin E level was increased to 8.1 ng/ml. 4. The levels of prostaglandin F2alpha in the exudate were as follows: At 8 h after the carrageenin injection, the level was 9.4 ng/ml, then decreased to 1.3 ng/ml and to 0.8 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the carrageenin injection, it was again elevated to 4.7 ng/ml. 5. The exudate of granuloma, 24 and 72 h after the carrageenin injection, was incubated with [3H]prostaglandin E1 at 37 degrees C for 30 min. Then the acidic ether extract was subjected to reversed phase partition chromatography. It was found that the exudate of 24 h and 72 h granuloma had little activity of prostaglandin 15alpha-hydroxy dehydrogenase.", "contents": "The content of prostaglandin E and prostaglandin F2alpha in the exudate of carrageenin granuloma of rats. 1. Granuloma was made by the subcutaneous injection of 2% carrageenin solution on the dorsum of male rats. Eight, 16, 24 and 72 h after the injection. the exudate from each rat granuloma was withdrawn and extracted for rpstaglandins. 2. Extracted prostaglandins were separated prostaglandin E and prostaglandin F group by silicic acid mini-column chromatography. Then the amount of prostaglandin E and prostaglandin F2alpha were determined by the radioimmunoassay method. 3. The levels of prostaglandin E in the granuloma exudates were 4.6 ng/ml at 8 h after the carrageenin injection, then decreased 3.6 ng/ml and to 1.1 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the injection, prostaglandin E level was increased to 8.1 ng/ml. 4. The levels of prostaglandin F2alpha in the exudate were as follows: At 8 h after the carrageenin injection, the level was 9.4 ng/ml, then decreased to 1.3 ng/ml and to 0.8 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the carrageenin injection, it was again elevated to 4.7 ng/ml. 5. The exudate of granuloma, 24 and 72 h after the carrageenin injection, was incubated with [3H]prostaglandin E1 at 37 degrees C for 30 min. Then the acidic ether extract was subjected to reversed phase partition chromatography. It was found that the exudate of 24 h and 72 h granuloma had little activity of prostaglandin 15alpha-hydroxy dehydrogenase."} {"id": "PMID:177053", "title": "Combined enzymatic and chemical approaches to the synthesis of unique polyribonucleotides.", "content": "The enzymatic polymerization by polynucleotide phosphorylase of 6-chloro-9-(beta-D-ribofuranosyl)purine 5'-diphosphate to poly(6-chloropurinylic acid) and its conversion to poly(6-thioninosinic acid) is described. The sulfur isostere of poly(I) was found not to form a complex with poly(C), but to form a self-association complex with a Tm around 295 degrees K. The sedimentation velocities, pKa and Tm values of the polymer have been examined under various conditions. A two (or more) stranded helical array is suggested as the most probable structure. Thermal loss of the thione chromophore was noted for poly- (S6I), S6IMP and S6I; the degradation product from S6I was shown to be inosine.", "contents": "Combined enzymatic and chemical approaches to the synthesis of unique polyribonucleotides. The enzymatic polymerization by polynucleotide phosphorylase of 6-chloro-9-(beta-D-ribofuranosyl)purine 5'-diphosphate to poly(6-chloropurinylic acid) and its conversion to poly(6-thioninosinic acid) is described. The sulfur isostere of poly(I) was found not to form a complex with poly(C), but to form a self-association complex with a Tm around 295 degrees K. The sedimentation velocities, pKa and Tm values of the polymer have been examined under various conditions. A two (or more) stranded helical array is suggested as the most probable structure. Thermal loss of the thione chromophore was noted for poly- (S6I), S6IMP and S6I; the degradation product from S6I was shown to be inosine."} {"id": "PMID:177054", "title": "Stimulatory actions of thyrotropin and dibutyryl cyclic AMP on transcription and translation in the regulation of thyroidal protein synthesis.", "content": "When beef thyroid cells were incubated with thyrotropin and then tested for protein synthesizing activity, the stimulatory effect of thyrotropin appeared in two distinct phases: first, an immediate stimulation which continued as long as thyrotropin was present, but died away promptly after withdrawal of the added thyrotropin; and second, a delayed stimulation with a lag period of 1 to 2 h, which persisted after thyrotropin withdrawal. The fast and the delayed effects each stimulated protein synthesis by about 25%, so that after 4 h of thyrotropin treatment, total stimulation amounted to 50% above basal levels of activity. The fast thyrotropin effect was not affected by actinomycin D or cordycepin, and hence is evidently not dependent upon induced RNA synthesis. In contrast, the delayed thyrotropin effect was completely prevented by actinomycin D or cordycepin. These findings suggest that the fast effect of thyrotropin occurs at the translational level to provide for acute adjustments in thyroglobulin production by regulating the rate of translation of existing mRNA. The delayed thyrotropin effect, by initiating certain transcriptional reactions could be the means for selectively inducing the production of specific enzymes or proteins. Both the fast and delayed effects of thyrotropin were faithfully reproduced by dibutyryl cyclic AMP. This finding seems to be the first in vitro demonstration of a cyclic AMP induced transcriptional response to a hormone in mammalian cells.", "contents": "Stimulatory actions of thyrotropin and dibutyryl cyclic AMP on transcription and translation in the regulation of thyroidal protein synthesis. When beef thyroid cells were incubated with thyrotropin and then tested for protein synthesizing activity, the stimulatory effect of thyrotropin appeared in two distinct phases: first, an immediate stimulation which continued as long as thyrotropin was present, but died away promptly after withdrawal of the added thyrotropin; and second, a delayed stimulation with a lag period of 1 to 2 h, which persisted after thyrotropin withdrawal. The fast and the delayed effects each stimulated protein synthesis by about 25%, so that after 4 h of thyrotropin treatment, total stimulation amounted to 50% above basal levels of activity. The fast thyrotropin effect was not affected by actinomycin D or cordycepin, and hence is evidently not dependent upon induced RNA synthesis. In contrast, the delayed thyrotropin effect was completely prevented by actinomycin D or cordycepin. These findings suggest that the fast effect of thyrotropin occurs at the translational level to provide for acute adjustments in thyroglobulin production by regulating the rate of translation of existing mRNA. The delayed thyrotropin effect, by initiating certain transcriptional reactions could be the means for selectively inducing the production of specific enzymes or proteins. Both the fast and delayed effects of thyrotropin were faithfully reproduced by dibutyryl cyclic AMP. This finding seems to be the first in vitro demonstration of a cyclic AMP induced transcriptional response to a hormone in mammalian cells."} {"id": "PMID:177055", "title": "Stimulation of cartilage macromolecule synthesis by adenosine 3',5'-monophosphate.", "content": "The role of cyclic AMP in the regulation of cartilage macromolecule synthesis in vitro was studied in pelvic cartilage from 10-12 day chick embryos. Incubation of cartilages in medium containing 0.5 mM cyclic AMP resulted in a 30% inhibition of 35SO4-2, [3H]leucine and [3H]uridine incorporation into proteoglycan, total protein and RNA, respectively. Higher concentrations of cyclic AMP had no greater effects. In contrast, butyrylated cyclic AMP derivatives (0.5-5.0 mM) added to the incubation medium stimulated (50-100%) the incorporation of these radiolabeled precursors into cartilage macromolecules. Theophylline, in concentrations (0.1-0.5 mM) which raise intracellular cyclic AMP, also increases the incorporation of radiolabeled precursors into macromolecules. The data indicate that exogenous cyclic AMP and butyrylated cyclic AMP derivatives have paradoxical effects on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives, not exogenous cyclic AMP, mimic the effects of intracellular cyclic AMP. Incubation of embryonic chicken cartilage with exogenous cyclic AMP results in the extracellular degradation of the cyclic AMP to adenosine. Adenosine (0.125 mM) inhibits precursor incorporation into cartilage macromolecules. The metabolism of exogenous cyclic AMP generates sufficient adenosine to account for the observed inhibitory effects of exogenous cyclic AMP on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives are not degraded during incubation with cartilage. The data indicate that cartilage is a tissue in which the effect of cyclic AMP is to stimulate anabolic processes.", "contents": "Stimulation of cartilage macromolecule synthesis by adenosine 3',5'-monophosphate. The role of cyclic AMP in the regulation of cartilage macromolecule synthesis in vitro was studied in pelvic cartilage from 10-12 day chick embryos. Incubation of cartilages in medium containing 0.5 mM cyclic AMP resulted in a 30% inhibition of 35SO4-2, [3H]leucine and [3H]uridine incorporation into proteoglycan, total protein and RNA, respectively. Higher concentrations of cyclic AMP had no greater effects. In contrast, butyrylated cyclic AMP derivatives (0.5-5.0 mM) added to the incubation medium stimulated (50-100%) the incorporation of these radiolabeled precursors into cartilage macromolecules. Theophylline, in concentrations (0.1-0.5 mM) which raise intracellular cyclic AMP, also increases the incorporation of radiolabeled precursors into macromolecules. The data indicate that exogenous cyclic AMP and butyrylated cyclic AMP derivatives have paradoxical effects on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives, not exogenous cyclic AMP, mimic the effects of intracellular cyclic AMP. Incubation of embryonic chicken cartilage with exogenous cyclic AMP results in the extracellular degradation of the cyclic AMP to adenosine. Adenosine (0.125 mM) inhibits precursor incorporation into cartilage macromolecules. The metabolism of exogenous cyclic AMP generates sufficient adenosine to account for the observed inhibitory effects of exogenous cyclic AMP on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives are not degraded during incubation with cartilage. The data indicate that cartilage is a tissue in which the effect of cyclic AMP is to stimulate anabolic processes."} {"id": "PMID:177056", "title": "Non-lytic, non-ionic detergent extraction of plasma membrane constituents from normal and transformed fibroblasts.", "content": "A technique has been developed for the selective extraction of plasma membrane protein constituents from normal and transformed cell employing non-ionic detergents. The extraction procedure does not damage cells as judged by cell viability, 51Cr release, and trypan blue staining. Lactoperoxidase-catalyzed iodination followed by detergent extraction permits demonstration of a 100,000 dalton protein which is found on the surface of normal but not transformed hamster and mouse fibroblasts.", "contents": "Non-lytic, non-ionic detergent extraction of plasma membrane constituents from normal and transformed fibroblasts. A technique has been developed for the selective extraction of plasma membrane protein constituents from normal and transformed cell employing non-ionic detergents. The extraction procedure does not damage cells as judged by cell viability, 51Cr release, and trypan blue staining. Lactoperoxidase-catalyzed iodination followed by detergent extraction permits demonstration of a 100,000 dalton protein which is found on the surface of normal but not transformed hamster and mouse fibroblasts."} {"id": "PMID:177057", "title": "Morphological and biochemical characterization of light and heavy myelin isolated from developing rat brain.", "content": "Myelin from developing rat brains was separated on a discontinuous sucrose gradient into subfractions of two different densities, i.e. light and heavy myelin. Electron photomicrographs showed that heavy myelin consisted primarily of large compacted multilamellar structures with a distinct intraperiod line characteristic of myelin in situ. Light myelin, on the other hand, was composed of small vesicles having a unilamellar structure. Similar to whole myelin, both membrane subfractions were highly enriched in 2',3'-cyclic nucleotide-3'-phosphohydrolase. The specific activity of the enzyme, however, showed no developmental trend. Both subfractions contained all the four major proteins characteristic of the whole myelin membrane. There were, however, quantitative differences in the relative distribution of these proteins between light and heavy myelin. Basic protein accounted for 55% and proteolipid protein for 46% of the total myelin proteins of light and heavy myelin, respectively. DM-20 (Agrawal, H.C., Burton, R. M., Fishman, M.A., Mitchell, R.F. and Prensky, A.L. (1972) J. Neurochem. 19, 2083-2089) exhibited a developmental \"switch\" between light and heavy myelin. Light myelin appeared to contain more DM-20 in 15- to 20-day-old rat brain, whereas the concentration of this protein was higher in heavy myelin at subsequent ages studied.", "contents": "Morphological and biochemical characterization of light and heavy myelin isolated from developing rat brain. Myelin from developing rat brains was separated on a discontinuous sucrose gradient into subfractions of two different densities, i.e. light and heavy myelin. Electron photomicrographs showed that heavy myelin consisted primarily of large compacted multilamellar structures with a distinct intraperiod line characteristic of myelin in situ. Light myelin, on the other hand, was composed of small vesicles having a unilamellar structure. Similar to whole myelin, both membrane subfractions were highly enriched in 2',3'-cyclic nucleotide-3'-phosphohydrolase. The specific activity of the enzyme, however, showed no developmental trend. Both subfractions contained all the four major proteins characteristic of the whole myelin membrane. There were, however, quantitative differences in the relative distribution of these proteins between light and heavy myelin. Basic protein accounted for 55% and proteolipid protein for 46% of the total myelin proteins of light and heavy myelin, respectively. DM-20 (Agrawal, H.C., Burton, R. M., Fishman, M.A., Mitchell, R.F. and Prensky, A.L. (1972) J. Neurochem. 19, 2083-2089) exhibited a developmental \"switch\" between light and heavy myelin. Light myelin appeared to contain more DM-20 in 15- to 20-day-old rat brain, whereas the concentration of this protein was higher in heavy myelin at subsequent ages studied."} {"id": "PMID:177058", "title": "Altered surface topology and membrane functions of rat thymocytes eluted from nylon wool columns.", "content": "(1) Following incubation of thymocytes with nylon wool at 37 degrees C, the eluted cells showed an increase in the number of microvilli per cell and a concominant elongation of the microvilli (0.22 mum versus 1.15 mum. (2) Cyclic adenosine monophosphate (cylic AMP) levels were lowered by 30-50% in nylon wool-treated thymocytes. (3) Nylon wool-treated cells showed an impaired Na+-dependent amino acid transport system (2-aminoisobutyrate) whereas the Na+-independent amino acid transport system (1-aminocyclopentane-1-carboxylate) was unaffected.", "contents": "Altered surface topology and membrane functions of rat thymocytes eluted from nylon wool columns. (1) Following incubation of thymocytes with nylon wool at 37 degrees C, the eluted cells showed an increase in the number of microvilli per cell and a concominant elongation of the microvilli (0.22 mum versus 1.15 mum. (2) Cyclic adenosine monophosphate (cylic AMP) levels were lowered by 30-50% in nylon wool-treated thymocytes. (3) Nylon wool-treated cells showed an impaired Na+-dependent amino acid transport system (2-aminoisobutyrate) whereas the Na+-independent amino acid transport system (1-aminocyclopentane-1-carboxylate) was unaffected."} {"id": "PMID:177059", "title": "On the use of the spin labeling technique in the study of erythrocyte membranes.", "content": "ESR spectra and scanning electron micrographs of human erythrocytes spin labeled with the conventional stearic acid nitroxide substituted at the 5-position have been obtained over a range of label-to-lipid ratios. While morphological changes as previously reported (Bieri, V. G., Wallach, D. F. H. and Lin, P. S. (1974) Proc. Natl. Acad. Sci. U.S. 71, 4797-4801) are reproduced, it is shown that at label-to-lipid ratios of 1:10 or less the basic ESR spectrum is not significantly affected. At low label concentrations the spin labeling technique is a viable one and can be used to investigate membrane properties.", "contents": "On the use of the spin labeling technique in the study of erythrocyte membranes. ESR spectra and scanning electron micrographs of human erythrocytes spin labeled with the conventional stearic acid nitroxide substituted at the 5-position have been obtained over a range of label-to-lipid ratios. While morphological changes as previously reported (Bieri, V. G., Wallach, D. F. H. and Lin, P. S. (1974) Proc. Natl. Acad. Sci. U.S. 71, 4797-4801) are reproduced, it is shown that at label-to-lipid ratios of 1:10 or less the basic ESR spectrum is not significantly affected. At low label concentrations the spin labeling technique is a viable one and can be used to investigate membrane properties."} {"id": "PMID:177060", "title": "Endogenous cyclic AMP in thyroid cell culture. Effect of thyroid-stimulating hormone and dibutyryl cyclic AMP.", "content": "We have studied the variations of endogenous cyclic AMP levels in thyroid cells cultured over a period of 7 days in several conditions: in the presence of thyroid-stimulating hormone or dibutyryl cyclic AMP which both promote the aggregation of isolated cells into follicles, and in their absence when cells develop as a typical monolayer. In follicle-forming cells, the cyclic AMP level was found to rise during the first day of culture, then to fall rapidly. In monolayer-forming cells, the cyclic AMP content slightly increases attaining the same level as found in other cells at the fourth day, which remains stable till the seventh day. We have investigated the response of these cells cultured in the presence of dibutyryl cyclic AMP retain the capability of increasing their cyclic AMP concentration whereas monolayer-forming cells do not preserve this quality of thyroid cells.", "contents": "Endogenous cyclic AMP in thyroid cell culture. Effect of thyroid-stimulating hormone and dibutyryl cyclic AMP. We have studied the variations of endogenous cyclic AMP levels in thyroid cells cultured over a period of 7 days in several conditions: in the presence of thyroid-stimulating hormone or dibutyryl cyclic AMP which both promote the aggregation of isolated cells into follicles, and in their absence when cells develop as a typical monolayer. In follicle-forming cells, the cyclic AMP level was found to rise during the first day of culture, then to fall rapidly. In monolayer-forming cells, the cyclic AMP content slightly increases attaining the same level as found in other cells at the fourth day, which remains stable till the seventh day. We have investigated the response of these cells cultured in the presence of dibutyryl cyclic AMP retain the capability of increasing their cyclic AMP concentration whereas monolayer-forming cells do not preserve this quality of thyroid cells."} {"id": "PMID:177061", "title": "Sedimentation behavior of solubilized gonadotropin receptor from plasma membranes of bovine corpus luteum.", "content": "The gonadotropin receptors associated with plasma membrane fractions were solubilized by detergents, including Triton X-100, Lubrol WX, Lubrol PX and sodium deoxycholate before and after equilibration with 125I-labelled human chorionic gonadotropin. The binding activity remained in solution even after centrifugation at 300 000 X g for 3 h. The solubilized gonadotropin receptor or gonadotropin receptor complex was characterized by gel filtration and sucrose density gradient centrifugation. Sucrose density gradient centrifugation of solubilized gonadotropin-receptor complex in the presence of Triton X-100 had a sedimentation coefficient of 6.5 S whereas the solubilized uncomplexed receptor had a sedimentation coefficient of 5.1 S. In the absence of the detergent, solubilized hormone receptor complex from plasma membrane fractions I and II sedimented with an apparent sedimentation coefficient of 6.6 S and 7.4 S, respectively. Similarly, the free receptor also showed higher sedimentation profile with an apparent sedimentation coefficient of 6.7 S for fraction I and 7.2 S for fraction II. Treatment of plasma membranes with phospholipase A and C inhibited the binding of 125I-labelled human chorionic gonadotropin in a dose dependent manner, whereas phospholipase D was without any effect. Doses of 1.4 mI. U. of phospholipase A or 0.6 mI.U. of phospholipase C were required to produce 50% inhibition of the binding activity. These phospholipases had no effect on the preformed 125I-labelled human chorionic gonadotropin-receptor complex nor on the sedimentation profile of solubilized gonadotropin receptor complex.", "contents": "Sedimentation behavior of solubilized gonadotropin receptor from plasma membranes of bovine corpus luteum. The gonadotropin receptors associated with plasma membrane fractions were solubilized by detergents, including Triton X-100, Lubrol WX, Lubrol PX and sodium deoxycholate before and after equilibration with 125I-labelled human chorionic gonadotropin. The binding activity remained in solution even after centrifugation at 300 000 X g for 3 h. The solubilized gonadotropin receptor or gonadotropin receptor complex was characterized by gel filtration and sucrose density gradient centrifugation. Sucrose density gradient centrifugation of solubilized gonadotropin-receptor complex in the presence of Triton X-100 had a sedimentation coefficient of 6.5 S whereas the solubilized uncomplexed receptor had a sedimentation coefficient of 5.1 S. In the absence of the detergent, solubilized hormone receptor complex from plasma membrane fractions I and II sedimented with an apparent sedimentation coefficient of 6.6 S and 7.4 S, respectively. Similarly, the free receptor also showed higher sedimentation profile with an apparent sedimentation coefficient of 6.7 S for fraction I and 7.2 S for fraction II. Treatment of plasma membranes with phospholipase A and C inhibited the binding of 125I-labelled human chorionic gonadotropin in a dose dependent manner, whereas phospholipase D was without any effect. Doses of 1.4 mI. U. of phospholipase A or 0.6 mI.U. of phospholipase C were required to produce 50% inhibition of the binding activity. These phospholipases had no effect on the preformed 125I-labelled human chorionic gonadotropin-receptor complex nor on the sedimentation profile of solubilized gonadotropin receptor complex."} {"id": "PMID:177062", "title": "An adenosine 3':5' monophosphate dependent protein kinase from sea urchin spermatozoa.", "content": "A cyclic AMP dependent protein kinase (EC 2.7.1.37) from sea urchin sperm as purified to near homogeneity and characterized. A 68-fold purification of the enzyme was obtained. This preparation had a specific activity of 389 000 units/mg protein with protamine as the substrate. On the basis of the purification required, it may be calculated that the protein kinase constitutes as much as 1.5% of the soluble protein in sperm. There appeared to be a single form of the enzyme in sea urchin sperm, based on the behavior of the enzyme during DEAE-cellulose and Sephadex G-200 column chromatography. Magnesium ion was required for enzyme activity. The rate of phosphorylation of protamine was stimulated 2.5-fold by an optimal concentration of 0.9 M NaCl. The Km for ATP (minus cyclic AMP) was 0.119 +/- 0.013 (S.D.) and 0.055 mM +/- 0.009 (S.D.) in the presence of cyclic AMP. The specificity of the enzyme toward protein acceptors, in decreasing order of phosphorylation, was found to be histone f1 protamine, histone f2b, histone f3 and histone f2a; casein and phosvitin were not phosphorylated. The holoenzyme was found to have an apparent molecular weight of 230 000 by Sephadex G-200 chromatography. In the presence of 5 - 10(-6) M cyclic AMP, the holoenzyme was dissociated on Sephadex G-200 to a regulatory subunit of molecular weight 165 000 and a catalytic subunit of Mr 73 000. The dissociation could also be demonstrated by disc gel electrophoresis in the presence and absence of cyclic AMP.", "contents": "An adenosine 3':5' monophosphate dependent protein kinase from sea urchin spermatozoa. A cyclic AMP dependent protein kinase (EC 2.7.1.37) from sea urchin sperm as purified to near homogeneity and characterized. A 68-fold purification of the enzyme was obtained. This preparation had a specific activity of 389 000 units/mg protein with protamine as the substrate. On the basis of the purification required, it may be calculated that the protein kinase constitutes as much as 1.5% of the soluble protein in sperm. There appeared to be a single form of the enzyme in sea urchin sperm, based on the behavior of the enzyme during DEAE-cellulose and Sephadex G-200 column chromatography. Magnesium ion was required for enzyme activity. The rate of phosphorylation of protamine was stimulated 2.5-fold by an optimal concentration of 0.9 M NaCl. The Km for ATP (minus cyclic AMP) was 0.119 +/- 0.013 (S.D.) and 0.055 mM +/- 0.009 (S.D.) in the presence of cyclic AMP. The specificity of the enzyme toward protein acceptors, in decreasing order of phosphorylation, was found to be histone f1 protamine, histone f2b, histone f3 and histone f2a; casein and phosvitin were not phosphorylated. The holoenzyme was found to have an apparent molecular weight of 230 000 by Sephadex G-200 chromatography. In the presence of 5 - 10(-6) M cyclic AMP, the holoenzyme was dissociated on Sephadex G-200 to a regulatory subunit of molecular weight 165 000 and a catalytic subunit of Mr 73 000. The dissociation could also be demonstrated by disc gel electrophoresis in the presence and absence of cyclic AMP."} {"id": "PMID:177063", "title": "Nucleoside-dependent protein kinase from Trypanosoma gambiense.", "content": "A nucleoside-dependent protein kinase (EC 2.7.1.37) was partially purified from Trypanosoma gambiense, the pathogenic agent of sleeping sickness. This enzyme catalyzes the phosphorylation of histone and protamine. Various nucleosides at the concentration of 10(-4) M stimulated the histone kinase activity about two-fold, whereas cyclic AMP and cyclic GMP were without effect. The pH-optimum for histone phosphorylation was at about pH 7.0. The enzyme activity absolutely depends on Mg2+, Mn2+ or Co2+. The apparent Km-value for histone was 0.3 mg/ml and those for ATP were 2 - 10(-4) M and 6 - 10(-5) M in the absence or presence of 10(-4) M adenosine respectively. IDP and ADP complete with ATP. The inhibition constants were calculated to be 2 - 10(-4) M and 2.5 - 10(-4) M, respectively. The molecular weight of the histone kinase was found to be 95 000 by gel filtration and 88 000 by sedimentation in a sucrose gradient.", "contents": "Nucleoside-dependent protein kinase from Trypanosoma gambiense. A nucleoside-dependent protein kinase (EC 2.7.1.37) was partially purified from Trypanosoma gambiense, the pathogenic agent of sleeping sickness. This enzyme catalyzes the phosphorylation of histone and protamine. Various nucleosides at the concentration of 10(-4) M stimulated the histone kinase activity about two-fold, whereas cyclic AMP and cyclic GMP were without effect. The pH-optimum for histone phosphorylation was at about pH 7.0. The enzyme activity absolutely depends on Mg2+, Mn2+ or Co2+. The apparent Km-value for histone was 0.3 mg/ml and those for ATP were 2 - 10(-4) M and 6 - 10(-5) M in the absence or presence of 10(-4) M adenosine respectively. IDP and ADP complete with ATP. The inhibition constants were calculated to be 2 - 10(-4) M and 2.5 - 10(-4) M, respectively. The molecular weight of the histone kinase was found to be 95 000 by gel filtration and 88 000 by sedimentation in a sucrose gradient."} {"id": "PMID:177064", "title": "Characterization of protein phosphokinase activities in horse thyroid nuclei.", "content": "The distribution of protein phosphokinase (EC 2.7.1.37) activities has been established in horse thyroid nuclei. The presence of several enzyme activities has been demonstrated, two of which are clearly distinct. The first one acts on histone as substrate and is activated by cyclic AMP. Physico-chemical properties of this nuclear cyclic AMP-dependent histone kinase and of the cytosol histone kinase are different, demonstrating the absence of a contamination from the cytosol. The second enzyme acts on casein as substrate and is not stimulated by cyclic AMP POR CYCLIC GMP. The findings are consistent with the observation of thyrotropin stimulation of histone phosphorylation in thyroid nuclei.", "contents": "Characterization of protein phosphokinase activities in horse thyroid nuclei. The distribution of protein phosphokinase (EC 2.7.1.37) activities has been established in horse thyroid nuclei. The presence of several enzyme activities has been demonstrated, two of which are clearly distinct. The first one acts on histone as substrate and is activated by cyclic AMP. Physico-chemical properties of this nuclear cyclic AMP-dependent histone kinase and of the cytosol histone kinase are different, demonstrating the absence of a contamination from the cytosol. The second enzyme acts on casein as substrate and is not stimulated by cyclic AMP POR CYCLIC GMP. The findings are consistent with the observation of thyrotropin stimulation of histone phosphorylation in thyroid nuclei."} {"id": "PMID:177065", "title": "Activation of rat liver pyrimidine nucleoside monophosphate kinase.", "content": "The activity of the pyrimidine nucleoside monophosphate kinase (ATP:dCMP phosphotransferase, EC 2.7.4.14) from rat liver is dependent upon the presence of sulfhydryl-reducing agents. Addition to the inactive enzyme of 2-mercaptoethanol (5 mM), a reagent specific for cleavage of disulfide bonds, effects a reduction in molecular weight from approx. 53 000 to 17 000, measured by molecular sieve chromatography. This low molecular weight form is partially active in the presence of 2-mercaptoethanol (f mM). In absence of 2-mercaptoethanol, the low molecular weight form is inactive. Higher concentrations of 2-mercaptoethanol (50 mM) fully reactivate the CMP(ATP) kinase activity followed by dCMP(ATP) and CMP(dCTP) kinase activities in a sequential manner, without further change in moelcular weight. Alkylation by iodoacetamide of the enzyme at different stages of reactivation in dithiothreitol suggests an ordered appearance of the various enzyme activities. Furthermore, iodoacetamide inactivates the fully active enzyme. Thioredoxin was found to activate the enzyme in a manner similar to 2-mercaptoethanol and dithiothreitol. These results are consistent with the interpretation that the mechanism of activation of the enzyme involves cleavage of inter- and intramolecular disulfide bonds.", "contents": "Activation of rat liver pyrimidine nucleoside monophosphate kinase. The activity of the pyrimidine nucleoside monophosphate kinase (ATP:dCMP phosphotransferase, EC 2.7.4.14) from rat liver is dependent upon the presence of sulfhydryl-reducing agents. Addition to the inactive enzyme of 2-mercaptoethanol (5 mM), a reagent specific for cleavage of disulfide bonds, effects a reduction in molecular weight from approx. 53 000 to 17 000, measured by molecular sieve chromatography. This low molecular weight form is partially active in the presence of 2-mercaptoethanol (f mM). In absence of 2-mercaptoethanol, the low molecular weight form is inactive. Higher concentrations of 2-mercaptoethanol (50 mM) fully reactivate the CMP(ATP) kinase activity followed by dCMP(ATP) and CMP(dCTP) kinase activities in a sequential manner, without further change in moelcular weight. Alkylation by iodoacetamide of the enzyme at different stages of reactivation in dithiothreitol suggests an ordered appearance of the various enzyme activities. Furthermore, iodoacetamide inactivates the fully active enzyme. Thioredoxin was found to activate the enzyme in a manner similar to 2-mercaptoethanol and dithiothreitol. These results are consistent with the interpretation that the mechanism of activation of the enzyme involves cleavage of inter- and intramolecular disulfide bonds."} {"id": "PMID:177066", "title": "Procollagenase from bovine gingiva.", "content": "1. Collagenase (EC 3.4.24.3) is released from bovine gingival explants in vitro as a zymogen. The zymogen does not hydrolyze collagen and does not form a complex with alpha2-macroglobulin (alpha2-M). It elutes in gel filtration with an apparent molecular weight of approx. 80 000. 2. Incubation of the zymogen with trypsin results in a 15 000-20 000 dalton decrease in molecular weight and imparts to the enzyme the ability to hydrolyze collagen and to form a complex with alppha2-M. 3. The zymogen can be completely separated from the active enzyme to alpha2-M. Likewise, the zymogen can be harvested from cultures supplemented with serum.", "contents": "Procollagenase from bovine gingiva. 1. Collagenase (EC 3.4.24.3) is released from bovine gingival explants in vitro as a zymogen. The zymogen does not hydrolyze collagen and does not form a complex with alpha2-macroglobulin (alpha2-M). It elutes in gel filtration with an apparent molecular weight of approx. 80 000. 2. Incubation of the zymogen with trypsin results in a 15 000-20 000 dalton decrease in molecular weight and imparts to the enzyme the ability to hydrolyze collagen and to form a complex with alppha2-M. 3. The zymogen can be completely separated from the active enzyme to alpha2-M. Likewise, the zymogen can be harvested from cultures supplemented with serum."} {"id": "PMID:177067", "title": "Chemical characterization and study of the autodigestion of pure collagenase from Achromobacter iophagus.", "content": "Only one collagenase (EC 3.4.24.3) is produced by the non-pathogenic Achromobacter iophagus strain. The chromatography of the crude enzyme on DE-32 cellulose followed by gel filtration on Sephadex G-100 in the presence of 1 M sodium chloride led to the isolation of a homogeneous enzyme. Its specific activity (1.642 mukat/mg) represents the highest value ever obtained for a bacterial collagenase. The amino acid composition of A. iophagus collagenase differs from that of Clostridium histolyticum mainly in the sulfur-containing amino acids. 1 mol of zinc was found for 1 mol of enzyme of molecular weight 104 000. The autodegradation of the A. iophagus collagenase results in the formation of at least three active fractions which can be separated by preparative polyacrylamide gel electrophoresis as well as rechromatography on DE-32 cellulose. They are active towards the synthetic substrate as well as towards the native collagen. The results of ORD have shown that the digestion of the last one occurs in the helical parts of the substrate.", "contents": "Chemical characterization and study of the autodigestion of pure collagenase from Achromobacter iophagus. Only one collagenase (EC 3.4.24.3) is produced by the non-pathogenic Achromobacter iophagus strain. The chromatography of the crude enzyme on DE-32 cellulose followed by gel filtration on Sephadex G-100 in the presence of 1 M sodium chloride led to the isolation of a homogeneous enzyme. Its specific activity (1.642 mukat/mg) represents the highest value ever obtained for a bacterial collagenase. The amino acid composition of A. iophagus collagenase differs from that of Clostridium histolyticum mainly in the sulfur-containing amino acids. 1 mol of zinc was found for 1 mol of enzyme of molecular weight 104 000. The autodegradation of the A. iophagus collagenase results in the formation of at least three active fractions which can be separated by preparative polyacrylamide gel electrophoresis as well as rechromatography on DE-32 cellulose. They are active towards the synthetic substrate as well as towards the native collagen. The results of ORD have shown that the digestion of the last one occurs in the helical parts of the substrate."} {"id": "PMID:177068", "title": "Inhibition of hydroxyproline synthesis by palladium ions.", "content": "Palladium ions, administered as PdSO4, markedly affect the incorporation of L-[3,4-3H2] proline into non-dialyzable fractions in 10-day chick embryo cartilage explants with a 55-65% reduction in the concentration range 0.06-0.6 mM. Under these conditions the synthesis of [3H]hydroxyproline was nearly completely inhibited. Experiments with prolyl hydroxylase (EC 1.14.11.2) indicated a strong irreversible inhibition of the enzyme with a competition between Fe2+ and Pd2+. The Ki for the inhibition was 0.02 mM. Pd2+-treated enzyme remained inactive after extensive dialysis. These studies suggest that Pd2+ may inhibit collagen synthesis by replacing Fe2+ in the active site of prolyl hydroxylase and forming strong complexes with the enzyme. These studies also point to a potential mechanism of Pd2+ toxicity.", "contents": "Inhibition of hydroxyproline synthesis by palladium ions. Palladium ions, administered as PdSO4, markedly affect the incorporation of L-[3,4-3H2] proline into non-dialyzable fractions in 10-day chick embryo cartilage explants with a 55-65% reduction in the concentration range 0.06-0.6 mM. Under these conditions the synthesis of [3H]hydroxyproline was nearly completely inhibited. Experiments with prolyl hydroxylase (EC 1.14.11.2) indicated a strong irreversible inhibition of the enzyme with a competition between Fe2+ and Pd2+. The Ki for the inhibition was 0.02 mM. Pd2+-treated enzyme remained inactive after extensive dialysis. These studies suggest that Pd2+ may inhibit collagen synthesis by replacing Fe2+ in the active site of prolyl hydroxylase and forming strong complexes with the enzyme. These studies also point to a potential mechanism of Pd2+ toxicity."} {"id": "PMID:177069", "title": "[Research on subcellular localization of procollagen proline hydroxylase from chick embryo liver (author's transl)].", "content": "Subcellular fractionation by differential centrifugation was used to study protocollagen proline hydroxylase (EC 1.14.11.2) localization from chick embryo liver. The fractions have been characterized by marker enzymes and electron microscopy. By these methods, it was observed that procollagen-proline-hydroxylase is concentrated in the microsomal fraction which is sedimented at 145 000 X g in 250 mM sucrose.", "contents": "[Research on subcellular localization of procollagen proline hydroxylase from chick embryo liver (author's transl)]. Subcellular fractionation by differential centrifugation was used to study protocollagen proline hydroxylase (EC 1.14.11.2) localization from chick embryo liver. The fractions have been characterized by marker enzymes and electron microscopy. By these methods, it was observed that procollagen-proline-hydroxylase is concentrated in the microsomal fraction which is sedimented at 145 000 X g in 250 mM sucrose."} {"id": "PMID:177070", "title": "The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes.", "content": "Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.", "contents": "The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes. Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases."} {"id": "PMID:177071", "title": "Catalytic and regulatory properties of two forms of bovine heart cyclic nucleotide phosphodiesterase.", "content": "The soluble supernatant fraction of bovine heart homogenates may be fractionated on a DEAE cellulose column into two cyclic nucleotide phosphodiesterases (EC 3.1.4.-):PI and PII phosphodiesterases, in the order of emergence from the column. In the presence of free Ca2+, the PI enzyme may be activated several fold by the protein activator which was discovered by Cheung((1971) J. Biol. Chem. 246, 2859-2869). The PII enzyme is refractory to this activator, and is not inhibited by the Ca2+ chelating agent, ethylene glycol bis (beta-aminoethyl ether)-N, N'-tetraacetate (EGTA). The activated activity of PI phosphodiesterase may be further stimulated by imidazole or NH+4, and inhibited by high concentrations of Mg2+. These reagents have no significant effect on either the PII enzyme or the basal activity of PI phosphodiesterase. Although both forms of phosphodiesterase can hydrolyze either cyclic AMP or cyclic GMP, they exhibit different relative affinities towards these two cyclic nucleotides. The PI enzyme appears to have much higher affinities toward cyclic GMP than cyclic AMP. Km values for cyclic AMP and cyclic GMP are respectively 1.7 and 0.33 mM for the non-activated PI phosphodiesterase; and 0.2 and 0.007 mM for the activated enzyme. Each cyclic nucleotide acts as a competitive inhibitor for the other with Ki values similar to the respective Km values. In contrast with PI phosphodiesterase, PII phosphodiesterase exhibits similar affinity toward cyclic AMP and cyclic GMP. The apparent Km values of cyclic AMP and cyclic GMP for the PII enzyme are approx. 0.05 and 0.03 mM, respectively. The kinetic plot with respect to cyclic GMP shows positive cooperativity. Each cyclic nucleotide acts as a non-competitive inhibitor for the other nucleotide. These kinetic properties of PI and PII phosphodiesterase of bovine heart are very similar to those of rat liver cyclic GMP and high Km cyclic AMP phosphodiesterases, respectively (Russel, Terasaki and Appleman, (1973) J. Biol. Chem. 248, 1334).", "contents": "Catalytic and regulatory properties of two forms of bovine heart cyclic nucleotide phosphodiesterase. The soluble supernatant fraction of bovine heart homogenates may be fractionated on a DEAE cellulose column into two cyclic nucleotide phosphodiesterases (EC 3.1.4.-):PI and PII phosphodiesterases, in the order of emergence from the column. In the presence of free Ca2+, the PI enzyme may be activated several fold by the protein activator which was discovered by Cheung((1971) J. Biol. Chem. 246, 2859-2869). The PII enzyme is refractory to this activator, and is not inhibited by the Ca2+ chelating agent, ethylene glycol bis (beta-aminoethyl ether)-N, N'-tetraacetate (EGTA). The activated activity of PI phosphodiesterase may be further stimulated by imidazole or NH+4, and inhibited by high concentrations of Mg2+. These reagents have no significant effect on either the PII enzyme or the basal activity of PI phosphodiesterase. Although both forms of phosphodiesterase can hydrolyze either cyclic AMP or cyclic GMP, they exhibit different relative affinities towards these two cyclic nucleotides. The PI enzyme appears to have much higher affinities toward cyclic GMP than cyclic AMP. Km values for cyclic AMP and cyclic GMP are respectively 1.7 and 0.33 mM for the non-activated PI phosphodiesterase; and 0.2 and 0.007 mM for the activated enzyme. Each cyclic nucleotide acts as a competitive inhibitor for the other with Ki values similar to the respective Km values. In contrast with PI phosphodiesterase, PII phosphodiesterase exhibits similar affinity toward cyclic AMP and cyclic GMP. The apparent Km values of cyclic AMP and cyclic GMP for the PII enzyme are approx. 0.05 and 0.03 mM, respectively. The kinetic plot with respect to cyclic GMP shows positive cooperativity. Each cyclic nucleotide acts as a non-competitive inhibitor for the other nucleotide. These kinetic properties of PI and PII phosphodiesterase of bovine heart are very similar to those of rat liver cyclic GMP and high Km cyclic AMP phosphodiesterases, respectively (Russel, Terasaki and Appleman, (1973) J. Biol. Chem. 248, 1334)."} {"id": "PMID:177072", "title": "Protein inhibitor of cyclic adenosine 3':5'-monophosphate phosphodiesterase in retina.", "content": "A protein acting as inhibitor of cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.1.) activity was found in the ox retina tissue. An inhibitor from one tissue (ox retina) effectively cross-inhibited a phosphodiesterase from another tissue (rat brain), indicating a lack of tissue specificity. Kinetic analysis showed that inhibition was independent of the time of preliminary incubation of the inhibitor with enzyme but dependent on its concentration in the reaction mixture. An inhibitor decreased the V of the enzyme and had no effect on its Km for cyclic adenosine-3':5'-monophosphate. The inhibitory effect was more pronounced with cyclic adenosine-3':5'-monophosphate than with cyclic guanosine-3':5'-monophosphate used as substrates of the reaction. The extractable form of the phosphodiesterase of the retina rod outer segments was much more sensitive to the inhibitory action than the membrane-bound one. The binding of labeled cyclic adenosine-3':5'-monophosphate to the inhibitory protein was shown not to occur. The inhibitor was sensitive to trypsin treatment, indicating that it was a proten attempt was mode to purify the inhibitory factor. Gel filtration indicated that the inhibitor had a molecular weight of 38 000.", "contents": "Protein inhibitor of cyclic adenosine 3':5'-monophosphate phosphodiesterase in retina. A protein acting as inhibitor of cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.1.) activity was found in the ox retina tissue. An inhibitor from one tissue (ox retina) effectively cross-inhibited a phosphodiesterase from another tissue (rat brain), indicating a lack of tissue specificity. Kinetic analysis showed that inhibition was independent of the time of preliminary incubation of the inhibitor with enzyme but dependent on its concentration in the reaction mixture. An inhibitor decreased the V of the enzyme and had no effect on its Km for cyclic adenosine-3':5'-monophosphate. The inhibitory effect was more pronounced with cyclic adenosine-3':5'-monophosphate than with cyclic guanosine-3':5'-monophosphate used as substrates of the reaction. The extractable form of the phosphodiesterase of the retina rod outer segments was much more sensitive to the inhibitory action than the membrane-bound one. The binding of labeled cyclic adenosine-3':5'-monophosphate to the inhibitory protein was shown not to occur. The inhibitor was sensitive to trypsin treatment, indicating that it was a proten attempt was mode to purify the inhibitory factor. Gel filtration indicated that the inhibitor had a molecular weight of 38 000."} {"id": "PMID:177073", "title": "Human blood platelet 3': 5'-cyclic nucleotide phosphodiesterase. Isolation of low-Km and high-Km phosphodiesterase.", "content": "Human blood platelet contained at least three kinetically distinct forms of 3': 5'-cyclic nucleotide phosphodiesterase (3': 5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) (F I, F II, and F III) which were clearly separated by DEAE-cellulose column chromatography. Although a few properties of the platelet phosphodiesterases such as their substrate affinities and DEAE-cellulose profile resembled somewhat those of the three 3': 5'-cyclic nucleotide phosphodiesterase in rat liver reported by Russell et al. [10], there were pronounced differences in some properties between the platelet and the liver enzymes: (1) the platelet enzymes hydrolyzed both cyclic nucleotides and lacked a highly specific cyclic guanosine 3': 5'-monophosphate (cyclic GMP) phosphodiesterase and (2) kinetic data of the platelet enzymes indicated that cyclic adenosine 3': 5'-monophosphate (cyclic AMP) and cyclic GMP interact with a single catalytic site on the enzyme. F I was a cyclic nucleotide phosphodiesterase with a high Km for cyclic AMP and a negatively cooperative low Km for cyclic GMP. F II hydrolyzed cyclic AMP and cyclic GMP about equally with a high Km for both substrates. F III was low Km phosphodiesterase which hydrolyzed cyclic AMP faster than cyclic GMP. Each cyclic nucleotide acted as a competitive inhibitor of the hydrolysis of the other nucleotide by these three fractions with Ki values similar to the Km values for each nucleotide suggesting that the hydrolysis of both cyclic AMP and cyclic GMP was catalyzed by a single catalytic site on the enzyme. However, cyclic GMP at low concentration (below 10 muM) was an activator of cyclic AMP hydrolysis by F I. Papaverine and EG 626 acted as competitive inhibitors of each fraction with virtually the same Ki value in both assays using either cyclic AMP or cyclic GMP as the substrate. The ratio of cyclic AMP hydrolysis to cyclic GMP hydrolysis by each fraction did not vary significantly after freezing/thawing or heat treatment. These facts also suggest that both nucleotides were hydrolyzed by the same catalytic site on the enzyme. The differences in apparent Ki values for inhibitors such as cyclic nucleotides, papaverine and EG 626 would indicate that three enzymes were different from each other. Centrifugation in a continuous sucrose gradient revealed sedimentation coefficients F I and II had 8.9 S and F III 4.6 S. The molecular weight of these forms, determined by gel filtration on a Sepharose 6B column, were approx. 240 000 (F I and II) and 180 000 (F III). F III was purified extensively (70-fold) from homogenate, with a recovery of approximately 7%.", "contents": "Human blood platelet 3': 5'-cyclic nucleotide phosphodiesterase. Isolation of low-Km and high-Km phosphodiesterase. Human blood platelet contained at least three kinetically distinct forms of 3': 5'-cyclic nucleotide phosphodiesterase (3': 5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) (F I, F II, and F III) which were clearly separated by DEAE-cellulose column chromatography. Although a few properties of the platelet phosphodiesterases such as their substrate affinities and DEAE-cellulose profile resembled somewhat those of the three 3': 5'-cyclic nucleotide phosphodiesterase in rat liver reported by Russell et al. [10], there were pronounced differences in some properties between the platelet and the liver enzymes: (1) the platelet enzymes hydrolyzed both cyclic nucleotides and lacked a highly specific cyclic guanosine 3': 5'-monophosphate (cyclic GMP) phosphodiesterase and (2) kinetic data of the platelet enzymes indicated that cyclic adenosine 3': 5'-monophosphate (cyclic AMP) and cyclic GMP interact with a single catalytic site on the enzyme. F I was a cyclic nucleotide phosphodiesterase with a high Km for cyclic AMP and a negatively cooperative low Km for cyclic GMP. F II hydrolyzed cyclic AMP and cyclic GMP about equally with a high Km for both substrates. F III was low Km phosphodiesterase which hydrolyzed cyclic AMP faster than cyclic GMP. Each cyclic nucleotide acted as a competitive inhibitor of the hydrolysis of the other nucleotide by these three fractions with Ki values similar to the Km values for each nucleotide suggesting that the hydrolysis of both cyclic AMP and cyclic GMP was catalyzed by a single catalytic site on the enzyme. However, cyclic GMP at low concentration (below 10 muM) was an activator of cyclic AMP hydrolysis by F I. Papaverine and EG 626 acted as competitive inhibitors of each fraction with virtually the same Ki value in both assays using either cyclic AMP or cyclic GMP as the substrate. The ratio of cyclic AMP hydrolysis to cyclic GMP hydrolysis by each fraction did not vary significantly after freezing/thawing or heat treatment. These facts also suggest that both nucleotides were hydrolyzed by the same catalytic site on the enzyme. The differences in apparent Ki values for inhibitors such as cyclic nucleotides, papaverine and EG 626 would indicate that three enzymes were different from each other. Centrifugation in a continuous sucrose gradient revealed sedimentation coefficients F I and II had 8.9 S and F III 4.6 S. The molecular weight of these forms, determined by gel filtration on a Sepharose 6B column, were approx. 240 000 (F I and II) and 180 000 (F III). F III was purified extensively (70-fold) from homogenate, with a recovery of approximately 7%."} {"id": "PMID:177074", "title": "Cytochrome c dependent, antimycin-A resistant respiration in mitochondria from potato tuber (Solanum tuberosum L.). Influence of wounding and storage time on outer membrane NADH-cytochrome-c-reductase.", "content": "Cytochrome c has two stimulatory effects on respiration of mitochondria especially those from wounded potato tuber. In the first place a stimulation of succinate- and NADH-consuming, antimycin-A-sensitive respiration, which reaches a maximal value at low cytochrome c concentrations, has been found. In the second place, at higher concentrations of cytochrome c a stimulation of NADH-consuming respiration occurs, which is antimycin-A-resistant, but KCN-sensitive. This antimycin-A-resistant, NADH-consuming respiration is absent, when no cytochrome c is added to the reaction medium. It is insensitive to metal chelators, to which the antimycin-A-and KCN-resistant plant mitochondrial alternative oxidase is sensitive. By measurements of NADH-cytochrome c reductase activities a corresponding antimycin-A-resistant NADH-cytochrome c reductase has been found, which is insensitive to osmotic shock treatment. A localization of this antimycin-A-resistant electron transport with NADH as the electron donor in the outer mitochondrial membrane is likely. In the mitochondrial preparations cytochrome c might stimulate by acting as an electron-carrier between the outer membrane reductase and the inner membrane cytochrome oxidase. A big increase of the outer membrane mediated electron transport in the mitochondria has been observed after wounding of potato tuber tissue. The ability of the tissue to produce this electron transport pathway after wounding disappeared after prolonged storage of the tubers. A possible function of this electron transport pathway in fatty acid desaturation during the wound-reaction is suggested.", "contents": "Cytochrome c dependent, antimycin-A resistant respiration in mitochondria from potato tuber (Solanum tuberosum L.). Influence of wounding and storage time on outer membrane NADH-cytochrome-c-reductase. Cytochrome c has two stimulatory effects on respiration of mitochondria especially those from wounded potato tuber. In the first place a stimulation of succinate- and NADH-consuming, antimycin-A-sensitive respiration, which reaches a maximal value at low cytochrome c concentrations, has been found. In the second place, at higher concentrations of cytochrome c a stimulation of NADH-consuming respiration occurs, which is antimycin-A-resistant, but KCN-sensitive. This antimycin-A-resistant, NADH-consuming respiration is absent, when no cytochrome c is added to the reaction medium. It is insensitive to metal chelators, to which the antimycin-A-and KCN-resistant plant mitochondrial alternative oxidase is sensitive. By measurements of NADH-cytochrome c reductase activities a corresponding antimycin-A-resistant NADH-cytochrome c reductase has been found, which is insensitive to osmotic shock treatment. A localization of this antimycin-A-resistant electron transport with NADH as the electron donor in the outer mitochondrial membrane is likely. In the mitochondrial preparations cytochrome c might stimulate by acting as an electron-carrier between the outer membrane reductase and the inner membrane cytochrome oxidase. A big increase of the outer membrane mediated electron transport in the mitochondria has been observed after wounding of potato tuber tissue. The ability of the tissue to produce this electron transport pathway after wounding disappeared after prolonged storage of the tubers. A possible function of this electron transport pathway in fatty acid desaturation during the wound-reaction is suggested."} {"id": "PMID:177075", "title": "Catalytic activity of cytochromes c and c1 in mitochondria and submitochondrial particles.", "content": "1. Beef heart mitochondria have a cytochrome c1:c:aa3 ratio of 0.65:1.0:1.0 as isolated; Keilin-Hartree submitochondrial particles ahve a ratio of 0.65:0.4:1.0. More than 50% of the submitochondrial particle membrane is in the 'inverted' configuration, shielding the catalytically active cytochrome c. The 'endogenous' cytochrome c of particles turns over at a maximal rate between 450 and 550 s-1 during the oxidation of succinate or ascorbate plus TMPD; the maximal turnover rate for cytochrome c in mitochondria is 300-400 s-1, at 28 degrees-30 degrees C, pH 7.4. 2. Ascorbate plus N,N,N',N'-tetramethyl-p-phenylene diamine added to antimycin-treated particles induces anomalous absorption increases between 555 and 565 nm during the aerobic steady state, which disappear upon anaerobiosis; succinate addition abolishes this cycle and permits the partial resolution of cytochrome c1 and cytochrome c steady states at 552.5-547 nm and 550-556.5 nm, respectively. 3. Cytochrome c1 is rather more reduced than cytochrome c during the oxidation of succinate and of ascorbate + N,N,N',N'-tetramethyl-p-phenylene diamine in both mitochondria and submitochondrial particles; a near equilibrium condition exists between cytochromes c1 and c in the aerobic steady state, with a rate constant for the c1 leads to c reduction step greater than 10(3) s-1. 4. The greater apparent response of the c/aa3 electron transfer step to salts, the hyperbolic inhibition of succinate oxidation by azide and cyanide, and the kinetic behaviour of the succinate-cytochrome c reductase system, are all explicable in terms of a near-equilibrium condition prevailing at the c1/c step. Endogenous cytochrome c of mitochondria and submitochondrial particles is apparently largely bound to cytochrome aa3 units in situ. Cytochrome c1 can either reduce the cytochrome c-cytochrome aa3 complex directly, or requires only a small extra amount of cytochrome c to carry the full electron transfer flux.", "contents": "Catalytic activity of cytochromes c and c1 in mitochondria and submitochondrial particles. 1. Beef heart mitochondria have a cytochrome c1:c:aa3 ratio of 0.65:1.0:1.0 as isolated; Keilin-Hartree submitochondrial particles ahve a ratio of 0.65:0.4:1.0. More than 50% of the submitochondrial particle membrane is in the 'inverted' configuration, shielding the catalytically active cytochrome c. The 'endogenous' cytochrome c of particles turns over at a maximal rate between 450 and 550 s-1 during the oxidation of succinate or ascorbate plus TMPD; the maximal turnover rate for cytochrome c in mitochondria is 300-400 s-1, at 28 degrees-30 degrees C, pH 7.4. 2. Ascorbate plus N,N,N',N'-tetramethyl-p-phenylene diamine added to antimycin-treated particles induces anomalous absorption increases between 555 and 565 nm during the aerobic steady state, which disappear upon anaerobiosis; succinate addition abolishes this cycle and permits the partial resolution of cytochrome c1 and cytochrome c steady states at 552.5-547 nm and 550-556.5 nm, respectively. 3. Cytochrome c1 is rather more reduced than cytochrome c during the oxidation of succinate and of ascorbate + N,N,N',N'-tetramethyl-p-phenylene diamine in both mitochondria and submitochondrial particles; a near equilibrium condition exists between cytochromes c1 and c in the aerobic steady state, with a rate constant for the c1 leads to c reduction step greater than 10(3) s-1. 4. The greater apparent response of the c/aa3 electron transfer step to salts, the hyperbolic inhibition of succinate oxidation by azide and cyanide, and the kinetic behaviour of the succinate-cytochrome c reductase system, are all explicable in terms of a near-equilibrium condition prevailing at the c1/c step. Endogenous cytochrome c of mitochondria and submitochondrial particles is apparently largely bound to cytochrome aa3 units in situ. Cytochrome c1 can either reduce the cytochrome c-cytochrome aa3 complex directly, or requires only a small extra amount of cytochrome c to carry the full electron transfer flux."} {"id": "PMID:177076", "title": "The reduced nicotinamide adenine dinucleotide \"oxidase\" of Acholeplasma laidlawii membranes.", "content": "An NADH dehydrogenase possessing a specific activity 3-5 times that of membrane-bound enzyme was obtained by extraction of Acholeplasma laidlawii membranes with 9.0% ethanol at 43 degrees C. This dehydrogenase contained only trace amounts of iron (suggesting an uncoupled respiration), a flavin ratio of 1:2 FAD to FMN and 30-40% lipid. Its resistance to sedimentation is probably due to the high flotation density of the lipids. It efficiently utilized ferricyanide, menadione and dichlorophenol indophenol as electron acceptors, but not O2, ubiquinone Q10 or cytochrome c. Lineweaver-Burk plots of the dehydrogenase were altered to linear functions upon extraction with 9.0% ethanol. A secondary site of ferricyanide reduction could not be explained by the presence of cytochromes, which these membranes lack. In comparison to other respiratory chain-linked NADH dehydrogenases in cytochrome-containing respiratory chains, this dehydrogenase was characterized by similar Km's with ferricyanide, dichlorophenol indophenol, menadione as electron acceptors, but considerably smaller V's with ferricyanide, dichlorophenol indophenol, menadione as electron acceptors, and smaller specific activities. It was not stimulated or reactivated by the addition of FAD, FMN, Mg2+, cysteine or membrane lipids, and was less sensitive to respiratory inhibitors than unextracted enzyme. The ineffectiveness of ADP stimulation on O2 uptake, the insensitivity to oligomycin and the very low iron content of A. laidlawii membranes were considered in relation to conservation of energy by these cells. Some kinetic properties of the dehydrogenation, the uniquely high glycolipid content and apparently uncoupled respiration at Site I were noteworthy characteristics of this NADH dehydrogenase from the truncated respiratory chain of A. laidlawii.", "contents": "The reduced nicotinamide adenine dinucleotide \"oxidase\" of Acholeplasma laidlawii membranes. An NADH dehydrogenase possessing a specific activity 3-5 times that of membrane-bound enzyme was obtained by extraction of Acholeplasma laidlawii membranes with 9.0% ethanol at 43 degrees C. This dehydrogenase contained only trace amounts of iron (suggesting an uncoupled respiration), a flavin ratio of 1:2 FAD to FMN and 30-40% lipid. Its resistance to sedimentation is probably due to the high flotation density of the lipids. It efficiently utilized ferricyanide, menadione and dichlorophenol indophenol as electron acceptors, but not O2, ubiquinone Q10 or cytochrome c. Lineweaver-Burk plots of the dehydrogenase were altered to linear functions upon extraction with 9.0% ethanol. A secondary site of ferricyanide reduction could not be explained by the presence of cytochromes, which these membranes lack. In comparison to other respiratory chain-linked NADH dehydrogenases in cytochrome-containing respiratory chains, this dehydrogenase was characterized by similar Km's with ferricyanide, dichlorophenol indophenol, menadione as electron acceptors, but considerably smaller V's with ferricyanide, dichlorophenol indophenol, menadione as electron acceptors, and smaller specific activities. It was not stimulated or reactivated by the addition of FAD, FMN, Mg2+, cysteine or membrane lipids, and was less sensitive to respiratory inhibitors than unextracted enzyme. The ineffectiveness of ADP stimulation on O2 uptake, the insensitivity to oligomycin and the very low iron content of A. laidlawii membranes were considered in relation to conservation of energy by these cells. Some kinetic properties of the dehydrogenation, the uniquely high glycolipid content and apparently uncoupled respiration at Site I were noteworthy characteristics of this NADH dehydrogenase from the truncated respiratory chain of A. laidlawii."} {"id": "PMID:177077", "title": "RNA polymerases from a rat hepatoma. Partial purification and comparison of properties with corresponding liver enzymes.", "content": "DNA-dependent RNA polymerases were extracted from the nuclei of poorly differentiated tumor, Morris hepatoma 3924A, and purified by an initial chromatography on a DEAE-Sephadex column followed by fractionation on phosphocellulose and finally on a second DEAE-Sephadex column. Three major forms of RNA polymerase (IA, IB and II) were resolved chromatographically. Enzymes IA, IB and II eluted from DEAE-Sephadex at 75, 150 and 210 mM (NH4)2SO4, respectively. The specific activities (nmol UMP incorporated mg protein per 15 min) of polymerases IA, IB and II were 40, 43 and 182, respectively. Concurrently, DNA-dependent RNA polymerases were extracted from normal liver and subjected to similar chromatographic procedure. Upon the final DEAE-Sephadex chromatography, enzymes IA, IB and II eluted at 110, 180 and 210 mM (NH4)2SO4, respectively. The recovery of polymerases IA, IB and II after purification was 0.21, 0,28 and 0.42 unit/mg DNA, respectively, for hepatoma enzymes and 0.07, 0.05 and 0.42 unit/mg DNA for the corresponding liver enzymes.", "contents": "RNA polymerases from a rat hepatoma. Partial purification and comparison of properties with corresponding liver enzymes. DNA-dependent RNA polymerases were extracted from the nuclei of poorly differentiated tumor, Morris hepatoma 3924A, and purified by an initial chromatography on a DEAE-Sephadex column followed by fractionation on phosphocellulose and finally on a second DEAE-Sephadex column. Three major forms of RNA polymerase (IA, IB and II) were resolved chromatographically. Enzymes IA, IB and II eluted from DEAE-Sephadex at 75, 150 and 210 mM (NH4)2SO4, respectively. The specific activities (nmol UMP incorporated mg protein per 15 min) of polymerases IA, IB and II were 40, 43 and 182, respectively. Concurrently, DNA-dependent RNA polymerases were extracted from normal liver and subjected to similar chromatographic procedure. Upon the final DEAE-Sephadex chromatography, enzymes IA, IB and II eluted at 110, 180 and 210 mM (NH4)2SO4, respectively. The recovery of polymerases IA, IB and II after purification was 0.21, 0,28 and 0.42 unit/mg DNA, respectively, for hepatoma enzymes and 0.07, 0.05 and 0.42 unit/mg DNA for the corresponding liver enzymes."} {"id": "PMID:177078", "title": "Biosynthesis of plasma membrane components by SV40-virus-transformed 3T3 mouse cells temperature sensitive for expression of some transformed cell properties.", "content": "We have studied the plasma membranes of an SV40-transformed 3T3 cell line temperature sensitive for the transformed growth phenotype (ts H6-15 cells), and have found that they vary little as a function of temperature of cultivation. Analysis by polyacrylamide gel electrophoresis was performed on plasma membranes prepared from ts H6-15 cells cultured at the permissive (32 degrees C) and non-permissive (39 degrees C) temperatures and radioactively-labelled in several ways. No significant differences were seen when the electrophoretic patterns of polypeptides of the plasma membranes of ts H6-15 cells, grown through 3-4 generations in medium containing radioactive leucine (32 degrees C and 39 degrees C temperatures) were compared. Plasma membranes derived from cells similarly grown in medium with radioactive glucosamine indicated that extensive alterations in the intrinsic glycopeptides occurred in association with alteration in growth phenotype. A shift towards decreased synthesis of large molecular weight (congruent to 100 000-160 000) glycopeptides occurred in cells grown at the temperature of non-transformed growth (39 degrees C). A decrease in amount of a 120 000 molecular weight glycopeptide at 39 degrees C was the most prominent of these alterations. We have studied the surface exposure of polypeptides and glycopeptides of intact cells grown at 32 and 39 degrees C, using lactoperoxidase-catalyzed iodination, NaBH4 reduction of galactose oxidase-treated cells, and metabolic-labelling with glucosamine of trypsin-sensitive molecules. We found no major qualitative differences between whole cell extracts or between plasma membrane preparations of cells cultivated at the permissive and non-permissive temperatures. Of special interest was the observation that the formation and surface exposure of a trypsin-sensitive, 240 000 molecular weight polypeptide appeared not to be ts in ts H6-15 cells. The significance of these observations will be discussed.", "contents": "Biosynthesis of plasma membrane components by SV40-virus-transformed 3T3 mouse cells temperature sensitive for expression of some transformed cell properties. We have studied the plasma membranes of an SV40-transformed 3T3 cell line temperature sensitive for the transformed growth phenotype (ts H6-15 cells), and have found that they vary little as a function of temperature of cultivation. Analysis by polyacrylamide gel electrophoresis was performed on plasma membranes prepared from ts H6-15 cells cultured at the permissive (32 degrees C) and non-permissive (39 degrees C) temperatures and radioactively-labelled in several ways. No significant differences were seen when the electrophoretic patterns of polypeptides of the plasma membranes of ts H6-15 cells, grown through 3-4 generations in medium containing radioactive leucine (32 degrees C and 39 degrees C temperatures) were compared. Plasma membranes derived from cells similarly grown in medium with radioactive glucosamine indicated that extensive alterations in the intrinsic glycopeptides occurred in association with alteration in growth phenotype. A shift towards decreased synthesis of large molecular weight (congruent to 100 000-160 000) glycopeptides occurred in cells grown at the temperature of non-transformed growth (39 degrees C). A decrease in amount of a 120 000 molecular weight glycopeptide at 39 degrees C was the most prominent of these alterations. We have studied the surface exposure of polypeptides and glycopeptides of intact cells grown at 32 and 39 degrees C, using lactoperoxidase-catalyzed iodination, NaBH4 reduction of galactose oxidase-treated cells, and metabolic-labelling with glucosamine of trypsin-sensitive molecules. We found no major qualitative differences between whole cell extracts or between plasma membrane preparations of cells cultivated at the permissive and non-permissive temperatures. Of special interest was the observation that the formation and surface exposure of a trypsin-sensitive, 240 000 molecular weight polypeptide appeared not to be ts in ts H6-15 cells. The significance of these observations will be discussed."} {"id": "PMID:177079", "title": "Liver plasma membranes from essential fatty acid-deficient rats. Isolation, fatty acid composition, and activities of 5'-nucleotidase, ATPase and adenylate cyclase.", "content": "Tod determine whether changes in unsaturation of fatty acids in rat liver plasma membranes might alter activities of membrane-associated enzymes, liver plasma membranes were prepared from rats fed purified diets lacking or supplemented with essential fatty acids. Two methods of membrane purification were used. A similar degree of purification was obtained with both methods for both depleted and control membranes, as indicated by marker enzyme purification. The proportion of essential fatty acids of the linoleate series was significantly lower in phospholipids from depleted rats. The specific activity of 5'-nucleotidase was lower, and the activity, V and apparent Km for total (Na+ +K+ +Mg2+)-ATPase were higher in the depleted liver plasma membranes. Arrhenius plots of total ATPase activity showed a discontinuity at the same temperature for both the depleted and control membranes. Activity with the depleted membranes was higher at all temperatures tested. Supplementation of deficient rats with a source of essential fatty acids (corn oil) restored V and apparent Km values to normal. Adenylate cyclase activity in the presence of fluoride, glucagon or glucagon plus GTP was significantly lower in the depleted plasma membranes.", "contents": "Liver plasma membranes from essential fatty acid-deficient rats. Isolation, fatty acid composition, and activities of 5'-nucleotidase, ATPase and adenylate cyclase. Tod determine whether changes in unsaturation of fatty acids in rat liver plasma membranes might alter activities of membrane-associated enzymes, liver plasma membranes were prepared from rats fed purified diets lacking or supplemented with essential fatty acids. Two methods of membrane purification were used. A similar degree of purification was obtained with both methods for both depleted and control membranes, as indicated by marker enzyme purification. The proportion of essential fatty acids of the linoleate series was significantly lower in phospholipids from depleted rats. The specific activity of 5'-nucleotidase was lower, and the activity, V and apparent Km for total (Na+ +K+ +Mg2+)-ATPase were higher in the depleted liver plasma membranes. Arrhenius plots of total ATPase activity showed a discontinuity at the same temperature for both the depleted and control membranes. Activity with the depleted membranes was higher at all temperatures tested. Supplementation of deficient rats with a source of essential fatty acids (corn oil) restored V and apparent Km values to normal. Adenylate cyclase activity in the presence of fluoride, glucagon or glucagon plus GTP was significantly lower in the depleted plasma membranes."} {"id": "PMID:177080", "title": "Measurement of the translational mobility of concanavalin A in glycerol-saline solutions and on the cell surface by fluorescence recovery after photobleaching.", "content": "The fluorescence recovery kinetics of succinyl-fluorescein Concanavalin A (S-F-ConA) in glycerol-physiological saline solutions of high viscosity and when bound to the surface of mouse fibroblasts were measured following brief photobleaching using a laser excited fluorescence microscope. In the high viscosity solutions, the recovery kinetics, interpreted on the basis of a simple diffusion model, yielded a diffusion coefficient in close agreement with the values predicted by the Stokes-Einstein equation. Recovery kinetics for S-F-ConA bound to the surface of mouse 3T3 and SV3T3 cells cultured in vitro yielded diffusion coefficients in the range of 5-10-10(-11) cm2/s, values considerably lower than those reported previously for membrane proteins. These measurements indicated that a considerable fraction of the S-F-ConA molecules bound to the cell surface are immobilized. These results are discussed in relation to current concepts of lateral motion of protein components within natural membranes.", "contents": "Measurement of the translational mobility of concanavalin A in glycerol-saline solutions and on the cell surface by fluorescence recovery after photobleaching. The fluorescence recovery kinetics of succinyl-fluorescein Concanavalin A (S-F-ConA) in glycerol-physiological saline solutions of high viscosity and when bound to the surface of mouse fibroblasts were measured following brief photobleaching using a laser excited fluorescence microscope. In the high viscosity solutions, the recovery kinetics, interpreted on the basis of a simple diffusion model, yielded a diffusion coefficient in close agreement with the values predicted by the Stokes-Einstein equation. Recovery kinetics for S-F-ConA bound to the surface of mouse 3T3 and SV3T3 cells cultured in vitro yielded diffusion coefficients in the range of 5-10-10(-11) cm2/s, values considerably lower than those reported previously for membrane proteins. These measurements indicated that a considerable fraction of the S-F-ConA molecules bound to the cell surface are immobilized. These results are discussed in relation to current concepts of lateral motion of protein components within natural membranes."} {"id": "PMID:177081", "title": "Localization in the synaptic junction of the cyclic AMP stimulated intrinsic protein kinase activity of synaptosomal plasma membranes.", "content": "Synaptosomal plasma membrane fragments contain a tightly bound protein kinase which can catalyse the phosphorylation of endogenous protein the reaction bein stimulated by cyclic AMP. A fraction enriched in synaptic junctions, which can be isolated from Triton X-100-treated synaptosomal plasma membranes, is also enriched in the cyclic AMP stimulated intrinsic protein kinase. The location of the enzyme in the synaptic junction suggests that cyclic AMP-stimulated phosphorylation may have some role in synaptic transmission.", "contents": "Localization in the synaptic junction of the cyclic AMP stimulated intrinsic protein kinase activity of synaptosomal plasma membranes. Synaptosomal plasma membrane fragments contain a tightly bound protein kinase which can catalyse the phosphorylation of endogenous protein the reaction bein stimulated by cyclic AMP. A fraction enriched in synaptic junctions, which can be isolated from Triton X-100-treated synaptosomal plasma membranes, is also enriched in the cyclic AMP stimulated intrinsic protein kinase. The location of the enzyme in the synaptic junction suggests that cyclic AMP-stimulated phosphorylation may have some role in synaptic transmission."} {"id": "PMID:177082", "title": "Permeability properties of the membrane of vesicular stomatitis virions.", "content": "Observations of the light-scattering properties of several enveloped viruses indicate that virions (vesicular stomatitis, SV5 and influenza), in common with other membrane systems, are osmotically active, responding to NaCl gradients by swelling in hypo-osmolar solutions and shrinking in hyperosmolar solutions. The permeability barrier responsible for this osmotic response in vesicular stomatitis virions was modified both by protease treatment to remove the viral glycoprotein and by treatment with the polyene antibiotic filipin, an agent known to interact with cholesterol in liposomes and membranes. Filipin altered the kinetic and equilibrium permeability behavior of virions but the extent of leakage of osmotic shocking agent was less than that in lecithin/cholesterol and lecithin/ergosterol liposomes and in ergosterol-containing ciliary membranes. Negative-staining electron microscopy revealed that filipin treatment caused structural changes in the viral membrane. Intact virions exhibited appreciably larger responses to osmotic change than did protease-treated virus particles. Thus, the osmotic barrier in intact vesicular stomatitis virions may not be exclusively lipid in nature.", "contents": "Permeability properties of the membrane of vesicular stomatitis virions. Observations of the light-scattering properties of several enveloped viruses indicate that virions (vesicular stomatitis, SV5 and influenza), in common with other membrane systems, are osmotically active, responding to NaCl gradients by swelling in hypo-osmolar solutions and shrinking in hyperosmolar solutions. The permeability barrier responsible for this osmotic response in vesicular stomatitis virions was modified both by protease treatment to remove the viral glycoprotein and by treatment with the polyene antibiotic filipin, an agent known to interact with cholesterol in liposomes and membranes. Filipin altered the kinetic and equilibrium permeability behavior of virions but the extent of leakage of osmotic shocking agent was less than that in lecithin/cholesterol and lecithin/ergosterol liposomes and in ergosterol-containing ciliary membranes. Negative-staining electron microscopy revealed that filipin treatment caused structural changes in the viral membrane. Intact virions exhibited appreciably larger responses to osmotic change than did protease-treated virus particles. Thus, the osmotic barrier in intact vesicular stomatitis virions may not be exclusively lipid in nature."} {"id": "PMID:177085", "title": "[Two-dimensional immunoelectrophoresis of spontaneous dissociation of low density lipoproteins].", "content": "Plasma-lipoproteins isolated between d 1.020 and d 1.055 g/ml were partially delipidated with ethyl ether at 4 degrees C. This treatment induces a transformation of the lipoproteins which is evolutive during several days. Bidimensional immunoelectrophoresis reveals the lipoproteins dissociation and the appearance of 4 immunologically different fractions. The time dependent formation of these subunits is slowed down by EDTA and less efficiently by antioxydants. Once started, the dissociation can be accelerated by heating at 37 degrees C or by UV exposition. Another lipopeptide is more easily revealed by anti VLDL antiserum. It can be shown in the native and in the partially or completely delipidated LDL. Its presence does not depend on lipoprotein dissociation.", "contents": "[Two-dimensional immunoelectrophoresis of spontaneous dissociation of low density lipoproteins]. Plasma-lipoproteins isolated between d 1.020 and d 1.055 g/ml were partially delipidated with ethyl ether at 4 degrees C. This treatment induces a transformation of the lipoproteins which is evolutive during several days. Bidimensional immunoelectrophoresis reveals the lipoproteins dissociation and the appearance of 4 immunologically different fractions. The time dependent formation of these subunits is slowed down by EDTA and less efficiently by antioxydants. Once started, the dissociation can be accelerated by heating at 37 degrees C or by UV exposition. Another lipopeptide is more easily revealed by anti VLDL antiserum. It can be shown in the native and in the partially or completely delipidated LDL. Its presence does not depend on lipoprotein dissociation."} {"id": "PMID:177086", "title": "[Phospholipid composition and turnover in normal and SV40 transformed fibroblasts. Effect of cell density].", "content": "The phospholipid composition and turnover in normal and in SV 40 transformed hamster fibroblasts were studied. The amount of phospholipid phosphorus relative to protein is lower in transformed hamster fibroblasts than in normal fibroblasts. This amount decreases with increasing cell density until stationary growth is reached. The decrease is largest for the normal fibroblasts. In transformed cells, less sphingomyelin and more diphosphatidyl glycerol are found than in normal cells. The turnover of 32P in sphingomyelin is slower in transformed cells than in normal cells ; the contrary is observed with diphosphatidyl glycerol. On the other hand, in transformed cells, phosphatidyl ethanolamine has a faster turnover than phosphatidyl choline, whereas the contrary is observed in normal cells. Finally, the change to stationary growth slows down the turnover of 32P of all phospholipids, this decrease being more important in transformed cells.", "contents": "[Phospholipid composition and turnover in normal and SV40 transformed fibroblasts. Effect of cell density]. The phospholipid composition and turnover in normal and in SV 40 transformed hamster fibroblasts were studied. The amount of phospholipid phosphorus relative to protein is lower in transformed hamster fibroblasts than in normal fibroblasts. This amount decreases with increasing cell density until stationary growth is reached. The decrease is largest for the normal fibroblasts. In transformed cells, less sphingomyelin and more diphosphatidyl glycerol are found than in normal cells. The turnover of 32P in sphingomyelin is slower in transformed cells than in normal cells ; the contrary is observed with diphosphatidyl glycerol. On the other hand, in transformed cells, phosphatidyl ethanolamine has a faster turnover than phosphatidyl choline, whereas the contrary is observed in normal cells. Finally, the change to stationary growth slows down the turnover of 32P of all phospholipids, this decrease being more important in transformed cells."} {"id": "PMID:177087", "title": "Effect of substrate - binding on the immunologic reactivity of lobster - muscle arginine kinase : a comparison with rabbit - muscle creatine kinase.", "content": "The effects of substrate-binding upon the immunologic reactivity of rabbit creatine kinase and lobster arginine kinase have been investigated. The separate binding of the guanidine or the nucleotide substrate to creatine kinase yields no alteration of antigenicity and a substantial effect is only observed when all the loci at the active center of the enzyme, including that for the transferable phosphoryl group, are occupied. In contrast, the antigenic reactivity of arginine kinase is affected by the separate binding of either the guanidine or the nucleotide substrate, and the simultaneous binding of the two substrates results in a cumulative effect, which is irrespective of the phosphorylated or non-phosphorylated form of the complex. These results support the existence of substrate-induced conformational changes demonstrated by other methods, and they reveal appreciable differences in their effect on the antigenic reactivity of the two enzymes.", "contents": "Effect of substrate - binding on the immunologic reactivity of lobster - muscle arginine kinase : a comparison with rabbit - muscle creatine kinase. The effects of substrate-binding upon the immunologic reactivity of rabbit creatine kinase and lobster arginine kinase have been investigated. The separate binding of the guanidine or the nucleotide substrate to creatine kinase yields no alteration of antigenicity and a substantial effect is only observed when all the loci at the active center of the enzyme, including that for the transferable phosphoryl group, are occupied. In contrast, the antigenic reactivity of arginine kinase is affected by the separate binding of either the guanidine or the nucleotide substrate, and the simultaneous binding of the two substrates results in a cumulative effect, which is irrespective of the phosphorylated or non-phosphorylated form of the complex. These results support the existence of substrate-induced conformational changes demonstrated by other methods, and they reveal appreciable differences in their effect on the antigenic reactivity of the two enzymes."} {"id": "PMID:177091", "title": "[Isolation of peptide containing essential tyrosine from lobster arginine kinase].", "content": "The essential tyrosine residue of Lobster muscle arginine kinase, which is part of an antigenic determinant, has been modified by tetranitromethane. Cleavage of the S-carboxymethylated nitrated enzyme with cyanogen bromide gives rise to eight peptides, one of which containing the labelled essential tyrosyl group. Ion exchange chromatography on sulfoethyl-Sephadex C-25 in urea medium has been used with success for isolation and purification of the nitrated peptide. From its amino acid composition and end groups structure this peptide is the N-terminal fragment of the protein.", "contents": "[Isolation of peptide containing essential tyrosine from lobster arginine kinase]. The essential tyrosine residue of Lobster muscle arginine kinase, which is part of an antigenic determinant, has been modified by tetranitromethane. Cleavage of the S-carboxymethylated nitrated enzyme with cyanogen bromide gives rise to eight peptides, one of which containing the labelled essential tyrosyl group. Ion exchange chromatography on sulfoethyl-Sephadex C-25 in urea medium has been used with success for isolation and purification of the nitrated peptide. From its amino acid composition and end groups structure this peptide is the N-terminal fragment of the protein."} {"id": "PMID:177089", "title": "[Adenylate cyclase/Lipase. Hormone receptor induction].", "content": "An adenylate cyclase activity (AC) was found in guinea pig brown adipose tissue (BAT), since the tissue's apparition. This enzymatic activity increased during the development and showed high values at the end of gestation. An increase of AC units per cell was observed, in addition to the cell multiplication. A norepinephrine stimulation of AC activity was observed at the end of gestation : this regulating action disappeared in the first days of extrauterine life. Neither glucagon nor ACTH had any regulating role upon AC activity during fetal and newborn life. The basal lipolytic activity which was observed in BAT of fetuses (61rst day) and neonate dramatically around the 15th day. A potent lipolysis activation by norepinephrine was observed, but only after birth. The correlation observed between these enzymatic activities in presence of norepinephrine seems to indicate that the AC/lipase system was involved in the neonatal thermogenesis of guinea pigs.", "contents": "[Adenylate cyclase/Lipase. Hormone receptor induction]. An adenylate cyclase activity (AC) was found in guinea pig brown adipose tissue (BAT), since the tissue's apparition. This enzymatic activity increased during the development and showed high values at the end of gestation. An increase of AC units per cell was observed, in addition to the cell multiplication. A norepinephrine stimulation of AC activity was observed at the end of gestation : this regulating action disappeared in the first days of extrauterine life. Neither glucagon nor ACTH had any regulating role upon AC activity during fetal and newborn life. The basal lipolytic activity which was observed in BAT of fetuses (61rst day) and neonate dramatically around the 15th day. A potent lipolysis activation by norepinephrine was observed, but only after birth. The correlation observed between these enzymatic activities in presence of norepinephrine seems to indicate that the AC/lipase system was involved in the neonatal thermogenesis of guinea pigs."} {"id": "PMID:177097", "title": "Evidence for three enzymatic activities in one electrophoretic band of 3-phosphoglycerate mutase from red cells.", "content": "Electrophoresis of 3-phosphoglycerate mutase from erythrocytes of man and several animal species has been performed on cellulose acetate strips. In most cases the electrophoretic pattern of this enzymatic activity shows three bands. 2,3-diphosphoglycerate phosphatase and diphosphoglycerate mutase from erythrocytes of the same species have been revealed after migration during the same electrophoresis. We found that the band of 2,3-diphosphoglycerate phosphatase and the band of diphosphoglycerate mutase activities migrate at the same level as one of the bands corresponding to 3-phosphoglycerate mutase. Here, we discuss the possible existence of a single molecule carrying three enzymatic activities.", "contents": "Evidence for three enzymatic activities in one electrophoretic band of 3-phosphoglycerate mutase from red cells. Electrophoresis of 3-phosphoglycerate mutase from erythrocytes of man and several animal species has been performed on cellulose acetate strips. In most cases the electrophoretic pattern of this enzymatic activity shows three bands. 2,3-diphosphoglycerate phosphatase and diphosphoglycerate mutase from erythrocytes of the same species have been revealed after migration during the same electrophoresis. We found that the band of 2,3-diphosphoglycerate phosphatase and the band of diphosphoglycerate mutase activities migrate at the same level as one of the bands corresponding to 3-phosphoglycerate mutase. Here, we discuss the possible existence of a single molecule carrying three enzymatic activities."} {"id": "PMID:177111", "title": "Involvement of macrophages in genetic resistance to bone marrow grafts. Studies with two specific antimacrophage agents, carrageenan and silica.", "content": "Carrageenans and silica, agents toxic for macrophages, were used in this study to examine the role of macrophages in resistance of irradiated mice to inbred parental and rat bone marrow grafts. Administration of 2.5 mg of carrageenans or 2.5-5 mg of silica particles intravenously to prospective graft recipients resulted in a prompt abrogation of hybrid and xenogeneic resistance. The macrophage stabilizer poly-2-vinylpyridine N-oxide (PVNO) injected subcutaneously in the dose of 150 mg/kg, 24 hr before silica prevented or reduced the suppression of resistance. PVNO, however, did not antagonize the suppression of resistance by carrageenen, horse anti-mouse thymocyte serum and cyclophosphamide. These results suggest that a) a subpopulation is involved in marrow graft rejection by irradiated mice; b) carrageenan and silica apparently act on macrophages by different mechanisms c) horse anti-mouse thymocyte serum and cyclophosphamide may act on cells other than macrophages or they act on macrophages by a different mechanism than silica, to resistance to bone marrow transplantation.", "contents": "Involvement of macrophages in genetic resistance to bone marrow grafts. Studies with two specific antimacrophage agents, carrageenan and silica. Carrageenans and silica, agents toxic for macrophages, were used in this study to examine the role of macrophages in resistance of irradiated mice to inbred parental and rat bone marrow grafts. Administration of 2.5 mg of carrageenans or 2.5-5 mg of silica particles intravenously to prospective graft recipients resulted in a prompt abrogation of hybrid and xenogeneic resistance. The macrophage stabilizer poly-2-vinylpyridine N-oxide (PVNO) injected subcutaneously in the dose of 150 mg/kg, 24 hr before silica prevented or reduced the suppression of resistance. PVNO, however, did not antagonize the suppression of resistance by carrageenen, horse anti-mouse thymocyte serum and cyclophosphamide. These results suggest that a) a subpopulation is involved in marrow graft rejection by irradiated mice; b) carrageenan and silica apparently act on macrophages by different mechanisms c) horse anti-mouse thymocyte serum and cyclophosphamide may act on cells other than macrophages or they act on macrophages by a different mechanism than silica, to resistance to bone marrow transplantation."} {"id": "PMID:177112", "title": "Effect of cyproheptadine on the spontaneous diurnal variations of plasma ACTH-cortisol and ACTH-GH secretion induced by l-dopa.", "content": "Cyproheptadine administration resulted in marked reduction and complete inhibition of the GH and ACTH-cortisol responses to L-dopa in a group of healthy subjects. If this drug acts by antagonizing serotonin, as assumed, this study suggests that serotonin is also involved in L-dopa induced GH and ACTH release.", "contents": "Effect of cyproheptadine on the spontaneous diurnal variations of plasma ACTH-cortisol and ACTH-GH secretion induced by l-dopa. Cyproheptadine administration resulted in marked reduction and complete inhibition of the GH and ACTH-cortisol responses to L-dopa in a group of healthy subjects. If this drug acts by antagonizing serotonin, as assumed, this study suggests that serotonin is also involved in L-dopa induced GH and ACTH release."} {"id": "PMID:177113", "title": "Interferon induction by a tumoral DNA in an homologous culture system.", "content": "The interferon induction by Rous sarcoma DNA in an homologous culture system and a further insight of its kinetics and antimetabolites action were the principal aim of the present study. There was a direct relation between the dose of the inducer and the protection against the cytoplathogenic effect of the challenging virus (VSV) reaching the highest activity (68-75% CPE inhibition) with 100 mug RS-DNA. The kinetics of the induction revealed a peak inhibition by 18 hours after the inducer. Treatment with Actinomycin D evidenced that both interferon production and activity are modified. Its early addition resulted in a poor protection; but an accentuated interferon release was observed when antimetabolite was added 18 hours after the inducer. Similar results were obtained when its effect was studied on the activity of exogenous interferon. Interferon induction by Rous sarcoma DNA in an homologous system, allows the detection of a difference between tumoral and normal DNA at a biological level.", "contents": "Interferon induction by a tumoral DNA in an homologous culture system. The interferon induction by Rous sarcoma DNA in an homologous culture system and a further insight of its kinetics and antimetabolites action were the principal aim of the present study. There was a direct relation between the dose of the inducer and the protection against the cytoplathogenic effect of the challenging virus (VSV) reaching the highest activity (68-75% CPE inhibition) with 100 mug RS-DNA. The kinetics of the induction revealed a peak inhibition by 18 hours after the inducer. Treatment with Actinomycin D evidenced that both interferon production and activity are modified. Its early addition resulted in a poor protection; but an accentuated interferon release was observed when antimetabolite was added 18 hours after the inducer. Similar results were obtained when its effect was studied on the activity of exogenous interferon. Interferon induction by Rous sarcoma DNA in an homologous system, allows the detection of a difference between tumoral and normal DNA at a biological level."} {"id": "PMID:177114", "title": "An inhibitor of hepatoma cells multiplication in the efferent fluid from isolated perfused rat liver.", "content": "Efferent fluid from isolated rat livers perfused with a synthetic medium, when concentrated, inhibits the multiplication of hepatoma LF 20 cells \"in vitro\". The inhibitory factor is thermolabile, and is inactivated at a slow rate by proteolytic enzymes. Sephadex and Acrylamide-agarose chromatographic fractionation leads us to assume a molecular weight around 100,000 for the inhibitory factor. The release of the factor by the perfused liver depends on the temperature of the perfusing fluid. Potential role of this factor in the control of liver cell proliferation is discussed.", "contents": "An inhibitor of hepatoma cells multiplication in the efferent fluid from isolated perfused rat liver. Efferent fluid from isolated rat livers perfused with a synthetic medium, when concentrated, inhibits the multiplication of hepatoma LF 20 cells \"in vitro\". The inhibitory factor is thermolabile, and is inactivated at a slow rate by proteolytic enzymes. Sephadex and Acrylamide-agarose chromatographic fractionation leads us to assume a molecular weight around 100,000 for the inhibitory factor. The release of the factor by the perfused liver depends on the temperature of the perfusing fluid. Potential role of this factor in the control of liver cell proliferation is discussed."} {"id": "PMID:177115", "title": "Activity of human adenylate cyclase from human fat cell membranes.", "content": "Purified adipocytes plasma membranes have been prepared from human adipose tissue. The presence of an adenylate cyclase sensitive to epinephrine and fluoride has been demonstrated. Activation of the adenylate cyclase was usually 2 to 4 fold in the presence of epinephrine 5.10-5M and 8 to 10 fold in the presence of fluoride 10 mM. The adenylate cyclase from human adipose tissue was insensitive to glucagon and ACTH; these results are in support of previous studies of lipolysis in isolated fact cells or tissue fragments from human adipose tissue.", "contents": "Activity of human adenylate cyclase from human fat cell membranes. Purified adipocytes plasma membranes have been prepared from human adipose tissue. The presence of an adenylate cyclase sensitive to epinephrine and fluoride has been demonstrated. Activation of the adenylate cyclase was usually 2 to 4 fold in the presence of epinephrine 5.10-5M and 8 to 10 fold in the presence of fluoride 10 mM. The adenylate cyclase from human adipose tissue was insensitive to glucagon and ACTH; these results are in support of previous studies of lipolysis in isolated fact cells or tissue fragments from human adipose tissue."} {"id": "PMID:177116", "title": "Characterization of Epstein-Barr virus (EBV) antigens II. Detection of early antigen (S) using anticomplement immunofluorescence (ACIF) et complement fixation (CF) tests.", "content": "Using human sera having antibodies against Epstein-Barr virus (EBV) early antigens (EA) but lacking antibodies directed against the EB nuclear antigen (EBNA), the detection of EBV/EA was possible both by the anticomplement immunofluorescent test (ACIF) and by the classical complement fixation test (CF). The latter is particularly suitable for biochemical studies on EA.", "contents": "Characterization of Epstein-Barr virus (EBV) antigens II. Detection of early antigen (S) using anticomplement immunofluorescence (ACIF) et complement fixation (CF) tests. Using human sera having antibodies against Epstein-Barr virus (EBV) early antigens (EA) but lacking antibodies directed against the EB nuclear antigen (EBNA), the detection of EBV/EA was possible both by the anticomplement immunofluorescent test (ACIF) and by the classical complement fixation test (CF). The latter is particularly suitable for biochemical studies on EA."} {"id": "PMID:177117", "title": "Letter: In vitro induction of EBV early antigens in NPC epithelial tumour cells by IUDR or superinfection.", "content": "Induction of early antigens in the epithelial tumour cells of NPC was achieved both by IUDR treatment and EBV superinfection.", "contents": "Letter: In vitro induction of EBV early antigens in NPC epithelial tumour cells by IUDR or superinfection. Induction of early antigens in the epithelial tumour cells of NPC was achieved both by IUDR treatment and EBV superinfection."} {"id": "PMID:177118", "title": "Magnetic resonance distinction between site bound and atmospherically bound paramagnetic counterions in polyelectrolyte solutions.", "content": "A combination of the water protons NMR chemical shifts, longitudinal and transversal relaxation rates and of the paramagnetic counterion EPR signal is shown to provide a clear distinction between site binding, atmospheric trapping and free counterions in solutions of polyelectrolyte TMA salts with increasing concentrations of the divalent counterions Co++ and Mn++. Site binding is defined by the loss of water in the counterion first hydration shell while atmospheric binding results in a change in the counterion correlation time as compared to a free ion.", "contents": "Magnetic resonance distinction between site bound and atmospherically bound paramagnetic counterions in polyelectrolyte solutions. A combination of the water protons NMR chemical shifts, longitudinal and transversal relaxation rates and of the paramagnetic counterion EPR signal is shown to provide a clear distinction between site binding, atmospheric trapping and free counterions in solutions of polyelectrolyte TMA salts with increasing concentrations of the divalent counterions Co++ and Mn++. Site binding is defined by the loss of water in the counterion first hydration shell while atmospheric binding results in a change in the counterion correlation time as compared to a free ion."} {"id": "PMID:177121", "title": "[Morphofunctional state of the digestive tract in the early stages of atherosclerosis].", "content": "Cholesterol, alpha- and beta-lipoproteids, serotonin were determined in the blood serum of dogs which were on atherogenic diet for 2 months. The serotonin content was examined in various parts of the gastrointestinal tract (GIT). Parallel studies of the structural changes were carried out in the vascular system (VS) and various parts of the GIT. There was found a direct correlation between a rise in the cholesterol and serotonin level in the blood and serotonin in the GIT tissues. The initial stages of atherosclerotic changes were revealed in the vascular system. Along with compensatory-adaptive changes detected in the duodenum and the upper protions of the small intestine, initial stages of dystrophic-atrophic processes were observed in the lower portions. Comparative analysis of biochemical and morphological data indicated that disturbances of the morphofunctional state in the GIT played an important role in the genesis of the early stages of atherosclerosis.", "contents": "[Morphofunctional state of the digestive tract in the early stages of atherosclerosis]. Cholesterol, alpha- and beta-lipoproteids, serotonin were determined in the blood serum of dogs which were on atherogenic diet for 2 months. The serotonin content was examined in various parts of the gastrointestinal tract (GIT). Parallel studies of the structural changes were carried out in the vascular system (VS) and various parts of the GIT. There was found a direct correlation between a rise in the cholesterol and serotonin level in the blood and serotonin in the GIT tissues. The initial stages of atherosclerotic changes were revealed in the vascular system. Along with compensatory-adaptive changes detected in the duodenum and the upper protions of the small intestine, initial stages of dystrophic-atrophic processes were observed in the lower portions. Comparative analysis of biochemical and morphological data indicated that disturbances of the morphofunctional state in the GIT played an important role in the genesis of the early stages of atherosclerosis."} {"id": "PMID:177122", "title": "[Comparative characteristics of the fatty acid composition of lipoproteins in human blood plasma and aortic wall].", "content": "A study was made of a fatty acid composition of individual lipid fractions in the lipoproteids of the blood serum of a very low, low and high density, and the wall of the aorta affected with atherosclerosis. There was a close similarity between a fatty acid composition of phospholipids, triglycerides, and cholesterol esters of all the lipoproteid classes of the vascular wall and blood plasma. The fatty acid compostion of individual fractions proved to be similar in all the lipoproteid fractions. The lipids of the vascular wall not included into the lipoproteid composition differed considerably by their fatty acid composition from the lipids isolated from lipoproteids; lipids of the wall of the aorta contained much less unsaturated fatty acids than lipoproteids.", "contents": "[Comparative characteristics of the fatty acid composition of lipoproteins in human blood plasma and aortic wall]. A study was made of a fatty acid composition of individual lipid fractions in the lipoproteids of the blood serum of a very low, low and high density, and the wall of the aorta affected with atherosclerosis. There was a close similarity between a fatty acid composition of phospholipids, triglycerides, and cholesterol esters of all the lipoproteid classes of the vascular wall and blood plasma. The fatty acid compostion of individual fractions proved to be similar in all the lipoproteid fractions. The lipids of the vascular wall not included into the lipoproteid composition differed considerably by their fatty acid composition from the lipids isolated from lipoproteids; lipids of the wall of the aorta contained much less unsaturated fatty acids than lipoproteids."} {"id": "PMID:177123", "title": "[Effect on drugs changing the intracellular level of adenosine 3',5'-cyclic monophosphate on interferon formation in chick embryo cells of different ages].", "content": "The effect of theophylline and adrenaline on the synthesis of interferon induced by the influenza B virus, strain Lee, in a chick embryo tissue culture was studied. Both preparation were found to decrease interferon synthesis when 5-day-old cultures were used; the inhibitory effect was increased when the two drugs were used together. The degree of inhibition of interferon production depended on a dose of the preparation; the inhibition was still present even when the drugs ere introduced several hours after the cells were infected with interferonogen. The treatment of one-day-old cultures with theophylline resulted in increase of interferon synthesis, whereas administration of adrenaline alone or together with theophylline did not affect the level of interferon synthesis. The drugs used produced no effect on the reproduction of the test-virus of vesicular stomatitis, Newcastle disease and Chickungunya viruses in chick embryo cells and influenza B virus in the developing chick embryos. The results obtained are discussed from the point of view of a possible influence of the intracellular adenosine 3',5-cyclic monophosphate level on the synthesis of virus-induced interferon.", "contents": "[Effect on drugs changing the intracellular level of adenosine 3',5'-cyclic monophosphate on interferon formation in chick embryo cells of different ages]. The effect of theophylline and adrenaline on the synthesis of interferon induced by the influenza B virus, strain Lee, in a chick embryo tissue culture was studied. Both preparation were found to decrease interferon synthesis when 5-day-old cultures were used; the inhibitory effect was increased when the two drugs were used together. The degree of inhibition of interferon production depended on a dose of the preparation; the inhibition was still present even when the drugs ere introduced several hours after the cells were infected with interferonogen. The treatment of one-day-old cultures with theophylline resulted in increase of interferon synthesis, whereas administration of adrenaline alone or together with theophylline did not affect the level of interferon synthesis. The drugs used produced no effect on the reproduction of the test-virus of vesicular stomatitis, Newcastle disease and Chickungunya viruses in chick embryo cells and influenza B virus in the developing chick embryos. The results obtained are discussed from the point of view of a possible influence of the intracellular adenosine 3',5-cyclic monophosphate level on the synthesis of virus-induced interferon."} {"id": "PMID:177124", "title": "[Effect of carbidine on the process of adrenergic neurotransmission].", "content": "Methods of physiological analysis were applied to a study of the effect of an original psychotropic agent--carbidine--on the process of adrenergic neurotransmission on a model of an isolated rat Vas deferens. The noradrenaline (NA) content was determined in the same ductus spectrofluorimetrically; the capacity of the neuroleptic to block the consumption of the exogenous NA by the tissue was also investigated. Carbidine proved to possess an adrenomimetic effect caused by it capacity to release NA, leading to a reduction of endogenous neuromediator stores.", "contents": "[Effect of carbidine on the process of adrenergic neurotransmission]. Methods of physiological analysis were applied to a study of the effect of an original psychotropic agent--carbidine--on the process of adrenergic neurotransmission on a model of an isolated rat Vas deferens. The noradrenaline (NA) content was determined in the same ductus spectrofluorimetrically; the capacity of the neuroleptic to block the consumption of the exogenous NA by the tissue was also investigated. Carbidine proved to possess an adrenomimetic effect caused by it capacity to release NA, leading to a reduction of endogenous neuromediator stores."} {"id": "PMID:177125", "title": "[Autoradiographic study of human scirrhous gastric carcinoma during cultivation in diffusion chambers].", "content": "The growth of the epithelial and connective tissue cells was noted in cultivation of human schirrous carcinoma of the stomach in diffuse chambers. In difference to the initial tissue of the tumour in vitro in which no incorporation of thymidine-H3 into the connective tissue cells was noted, these cells proved to be labeled under conditions of growth in the chambers. One hour after the administration of thymidine-H3 the percentage of cells with labeled nuclei averaged 25.1% this considerably exceeding the value of the label index determined under conditions of incubation in vitro of the initial tumour tissue (6.6%). Under conditions of cultivation there was revealed a rapidly proliferating subpopulation of cells with the mitotic cycle duration of 14.8 hours.", "contents": "[Autoradiographic study of human scirrhous gastric carcinoma during cultivation in diffusion chambers]. The growth of the epithelial and connective tissue cells was noted in cultivation of human schirrous carcinoma of the stomach in diffuse chambers. In difference to the initial tissue of the tumour in vitro in which no incorporation of thymidine-H3 into the connective tissue cells was noted, these cells proved to be labeled under conditions of growth in the chambers. One hour after the administration of thymidine-H3 the percentage of cells with labeled nuclei averaged 25.1% this considerably exceeding the value of the label index determined under conditions of incubation in vitro of the initial tumour tissue (6.6%). Under conditions of cultivation there was revealed a rapidly proliferating subpopulation of cells with the mitotic cycle duration of 14.8 hours."} {"id": "PMID:177126", "title": "[Comparative study of the immune response of newborn and adult animals to the administration of tumor extracts].", "content": "Immunological reactivity to hepatoma 22a was studied in newborn and adult mice pretreated with tumour antigens. Treatment of newborn mice enhanced the growth rate of hepatoma 22a. Analogous treatment of adult mice resulted in the immunization effect. Evidently this difference was connected with a possible change of immunological reactivity to the tumour in newborn mice. This is supported by the results of cell dynamics--a mediated immunity assessed by the macrophage migration inhibition test. Splenic cells of the pretreated adult mice possessed the capacity to depress the macrophage migration more intensively in comparison with those of the pretreated newborn mice.", "contents": "[Comparative study of the immune response of newborn and adult animals to the administration of tumor extracts]. Immunological reactivity to hepatoma 22a was studied in newborn and adult mice pretreated with tumour antigens. Treatment of newborn mice enhanced the growth rate of hepatoma 22a. Analogous treatment of adult mice resulted in the immunization effect. Evidently this difference was connected with a possible change of immunological reactivity to the tumour in newborn mice. This is supported by the results of cell dynamics--a mediated immunity assessed by the macrophage migration inhibition test. Splenic cells of the pretreated adult mice possessed the capacity to depress the macrophage migration more intensively in comparison with those of the pretreated newborn mice."} {"id": "PMID:177127", "title": "[Methods of obtaining antisera against antigens of the mammary cancer virus].", "content": "The authors used various methods of producing virus-containing preparations from mouse mammary carcinoma to obtain rabbit antisera against the mammary carcinoma antigens. The best results were achieved by means of the virus precipitation from the cultural fluids of carcinomas growing in vitro after preliminary hormonal stimulation of the virus yield followed by its purification in the sucrose density gradient.", "contents": "[Methods of obtaining antisera against antigens of the mammary cancer virus]. The authors used various methods of producing virus-containing preparations from mouse mammary carcinoma to obtain rabbit antisera against the mammary carcinoma antigens. The best results were achieved by means of the virus precipitation from the cultural fluids of carcinomas growing in vitro after preliminary hormonal stimulation of the virus yield followed by its purification in the sucrose density gradient."} {"id": "PMID:177128", "title": "[Cyclic adenosine-3',5'-monophosphate level in donor plasma].", "content": "The method of competitive protein binding was applied to the study of content of cyclic adenosine-3',5'-monophosphate (cAMP) in donor plasma one day before and immediately after the donation of 200 ml of blood. The work was performed by Gilman's radiochemical method. Two types of reaction of donors to donorship were revealed: without any changes and with the changes of the cAMP level. In accordance with these reactions the donors were divided into two subgroups--the stable and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and at the time of blood recovery it increased even more particularly among persons of \"reactive\" type. In primary donors of reactive type the cAMP content before the blood donation was either below or over the mean value and either increased or decreased to the mean level after the blood loss.", "contents": "[Cyclic adenosine-3',5'-monophosphate level in donor plasma]. The method of competitive protein binding was applied to the study of content of cyclic adenosine-3',5'-monophosphate (cAMP) in donor plasma one day before and immediately after the donation of 200 ml of blood. The work was performed by Gilman's radiochemical method. Two types of reaction of donors to donorship were revealed: without any changes and with the changes of the cAMP level. In accordance with these reactions the donors were divided into two subgroups--the stable and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and at the time of blood recovery it increased even more particularly among persons of \"reactive\" type. In primary donors of reactive type the cAMP content before the blood donation was either below or over the mean value and either increased or decreased to the mean level after the blood loss."} {"id": "PMID:177129", "title": "[Changes in the noradrenaline level and synthesis of nuclear RNA in the brain of rats with disturbances of the emotions and conditioned-defense behavior].", "content": "Brain noradrenaline (Na) exhaustion in reserpine-, disulfiram-or diethyldithio carbamate-treated rats was followed by a fall of the nRNA synthesis, emotional and conditioned behaviour disturbances. In accumulation of cerebral NA (ipraside and imipramine injections) there is an increase in the rate of synthesis, of the nuclear RNA. Prevention of the exhausting effect of reserpine by a preliminary injection of ipraside also prevented disturbances of the nuclear RNA synthesis.", "contents": "[Changes in the noradrenaline level and synthesis of nuclear RNA in the brain of rats with disturbances of the emotions and conditioned-defense behavior]. Brain noradrenaline (Na) exhaustion in reserpine-, disulfiram-or diethyldithio carbamate-treated rats was followed by a fall of the nRNA synthesis, emotional and conditioned behaviour disturbances. In accumulation of cerebral NA (ipraside and imipramine injections) there is an increase in the rate of synthesis, of the nuclear RNA. Prevention of the exhausting effect of reserpine by a preliminary injection of ipraside also prevented disturbances of the nuclear RNA synthesis."} {"id": "PMID:177130", "title": "[Metabolism of liver polyphosphoisositides in rats during stimulating and depressing influences on the organism].", "content": "Under normal conditions the rate of the 32P-orthophosphate incorporation into the polyphosphoinositides was 30--40 times greater than into the other phospholipid fraction of the normal rat liver. There was a rapid postmortem alteration of the polyphosphoinositide content in the liver. Under conditions studied the changes in the phospholipid content were revealed in the polyphosphoinositide fractions only. The changes in the content and in the metabolic intensity of rat polyphosphoinositide in the liver were in many respects similar to those in the brain. Polyphosphoinositide fractions were found to be the most labile of all the phospholipid fractions in the rat liver.", "contents": "[Metabolism of liver polyphosphoisositides in rats during stimulating and depressing influences on the organism]. Under normal conditions the rate of the 32P-orthophosphate incorporation into the polyphosphoinositides was 30--40 times greater than into the other phospholipid fraction of the normal rat liver. There was a rapid postmortem alteration of the polyphosphoinositide content in the liver. Under conditions studied the changes in the phospholipid content were revealed in the polyphosphoinositide fractions only. The changes in the content and in the metabolic intensity of rat polyphosphoinositide in the liver were in many respects similar to those in the brain. Polyphosphoinositide fractions were found to be the most labile of all the phospholipid fractions in the rat liver."} {"id": "PMID:177131", "title": "[Phosphoinositides of the brain and liver of rats in ethanol poisoning].", "content": "Alcohol intoxication induced in the rat brain significant decrease in the monophosphoinositides level, but the di- and triphosphoinositides quantity did not change; the content of all the three studied fractions of the inositol-containing phospholipids in the liver decreased. The tendency to retain the normal level of di- and triphosphoinositides in the brain following alcohol intoxication may be considered as an important factor providing physiological condition of the brain metabolism.", "contents": "[Phosphoinositides of the brain and liver of rats in ethanol poisoning]. Alcohol intoxication induced in the rat brain significant decrease in the monophosphoinositides level, but the di- and triphosphoinositides quantity did not change; the content of all the three studied fractions of the inositol-containing phospholipids in the liver decreased. The tendency to retain the normal level of di- and triphosphoinositides in the brain following alcohol intoxication may be considered as an important factor providing physiological condition of the brain metabolism."} {"id": "PMID:177132", "title": "[Influence of nonakhlazin on adrenergic neurotransmission in the vas deferens of rats].", "content": "The effect of a new antianginal drug--nonachlazine on the adrenergic neurotransmission in the isolated rat vas deferens was studied by examining the vas deferens contractions in response to the transmural electric stimulation of the postganglionic sympathetic nerves and addition of noradrenaline (NA) or BaCl2. After the nonachlazine treatment the NA content in the vas deferens was also studied by the spectrofluorometric method. Besides, the effect of the drug on the uptake of the exogenous NA was investigated. Nonachlazine was found to possess some sympatholytic and spasmolytic effect and could block the uptake of the exogenous NA greatly.", "contents": "[Influence of nonakhlazin on adrenergic neurotransmission in the vas deferens of rats]. The effect of a new antianginal drug--nonachlazine on the adrenergic neurotransmission in the isolated rat vas deferens was studied by examining the vas deferens contractions in response to the transmural electric stimulation of the postganglionic sympathetic nerves and addition of noradrenaline (NA) or BaCl2. After the nonachlazine treatment the NA content in the vas deferens was also studied by the spectrofluorometric method. Besides, the effect of the drug on the uptake of the exogenous NA was investigated. Nonachlazine was found to possess some sympatholytic and spasmolytic effect and could block the uptake of the exogenous NA greatly."} {"id": "PMID:177133", "title": "In vitro colony-forming cells in the marrow of leukemic and preleukemic mice.", "content": "In vitro colony-forming cells (CFUc) were evaluated in preleukemic and leukemic AK mice. Increased concentrations of CFUc were found in normal appearing marrow of superinfected animals 2-3 wk prior to the onset of lymphoma. CFUc were present in marrows of mice with virus-accelerated, spontaneous, and transplanted lymphoma. CFUc concentration was often increased in mice with advanced disease and marrow replacement by lymphoblasts. When calculated on the basis of CFUc per normal marrow cells, this increase was marked. The colonies developed only in the presence of added colony-stimulating activity (CSA) and had the morphologic features of colonies from normal marrow. Leukemic cells did not form colonies. Lymphoma cells, from virus accelerated, spontaneous and transplanted lymphoma, did not produce CSA in feeder layers or conditioned medium. Leukemic and nonleukemic AK bone were found to produce similar small amounts of CSA. These studies showed that the preleukemic state as well as marrow replacement by lymphoblasts resulted in increased marrow CFUc's. No evidence for increased local production of CSA by lymphoblasts or the marrow microenvironment was found to account for this.", "contents": "In vitro colony-forming cells in the marrow of leukemic and preleukemic mice. In vitro colony-forming cells (CFUc) were evaluated in preleukemic and leukemic AK mice. Increased concentrations of CFUc were found in normal appearing marrow of superinfected animals 2-3 wk prior to the onset of lymphoma. CFUc were present in marrows of mice with virus-accelerated, spontaneous, and transplanted lymphoma. CFUc concentration was often increased in mice with advanced disease and marrow replacement by lymphoblasts. When calculated on the basis of CFUc per normal marrow cells, this increase was marked. The colonies developed only in the presence of added colony-stimulating activity (CSA) and had the morphologic features of colonies from normal marrow. Leukemic cells did not form colonies. Lymphoma cells, from virus accelerated, spontaneous and transplanted lymphoma, did not produce CSA in feeder layers or conditioned medium. Leukemic and nonleukemic AK bone were found to produce similar small amounts of CSA. These studies showed that the preleukemic state as well as marrow replacement by lymphoblasts resulted in increased marrow CFUc's. No evidence for increased local production of CSA by lymphoblasts or the marrow microenvironment was found to account for this."} {"id": "PMID:177134", "title": "Abnormal parachloromercuriphenylsulfonate-sensitive cation channel in the erythrocytes of hereditary spherocytosis.", "content": "The erythrocytes of hereditary spherocytosis (HS) demonstrate an increased inward movement of sodium ions, an alteration which has been proposed as the primary defect leading to cell destruction. Parachloromercuriphenylsulfonate (PCMBS), an agent reacting with sulfhydryl groups of the membrane, increases the cation permeability of normal red cells, but does so to a much lesser extent in the HS red cells. On the other hand, pronase that is specific for amino groups of the membrane increases cation permeability and decreases anion permeability equally in normal and HS red cells. It may be postulated that a decreased number of sulfhydryl sites or a mutation of proteins in the PCMBS-sensitive cation channels of the HS cell membrane result in this hyposensitivity to PCMBS.", "contents": "Abnormal parachloromercuriphenylsulfonate-sensitive cation channel in the erythrocytes of hereditary spherocytosis. The erythrocytes of hereditary spherocytosis (HS) demonstrate an increased inward movement of sodium ions, an alteration which has been proposed as the primary defect leading to cell destruction. Parachloromercuriphenylsulfonate (PCMBS), an agent reacting with sulfhydryl groups of the membrane, increases the cation permeability of normal red cells, but does so to a much lesser extent in the HS red cells. On the other hand, pronase that is specific for amino groups of the membrane increases cation permeability and decreases anion permeability equally in normal and HS red cells. It may be postulated that a decreased number of sulfhydryl sites or a mutation of proteins in the PCMBS-sensitive cation channels of the HS cell membrane result in this hyposensitivity to PCMBS."} {"id": "PMID:177135", "title": "[Immunologic status in Hodgkin patients: correlation with Epstein-Barr virus titers].", "content": "1. In Hodgkin's disease patient's immunological in vitro and in vivo parameters are of prognostic importance. 2. Skin test reactivity correlates to peripheral T-lymphocyte counts and Con A induced lymphoblastogenesis. 3. Con A is the most sensitive in vitro indicator for detecting latent immunodeficiency. 4. Hodgkin patients in long term remission after tumor reductive therapy exhibit a qualitative and quantitative lymphocyte defect. 5. In Hodgkin patients Herpes virus related antibody titers are elevated against Epstein Barr virus (EBV). The elevation coincides with a decreased T-cell number and function. Antibodies against other Herpes viruses (HSV, CMV, VZV) are in the normal range, when tested by the complement fixation method.", "contents": "[Immunologic status in Hodgkin patients: correlation with Epstein-Barr virus titers]. 1. In Hodgkin's disease patient's immunological in vitro and in vivo parameters are of prognostic importance. 2. Skin test reactivity correlates to peripheral T-lymphocyte counts and Con A induced lymphoblastogenesis. 3. Con A is the most sensitive in vitro indicator for detecting latent immunodeficiency. 4. Hodgkin patients in long term remission after tumor reductive therapy exhibit a qualitative and quantitative lymphocyte defect. 5. In Hodgkin patients Herpes virus related antibody titers are elevated against Epstein Barr virus (EBV). The elevation coincides with a decreased T-cell number and function. Antibodies against other Herpes viruses (HSV, CMV, VZV) are in the normal range, when tested by the complement fixation method."} {"id": "PMID:177136", "title": "[Biochemical study of the human palmar aponeurosis under normal and pathological conditions].", "content": "Study of oxyproline content of the palmar aponeurosis connective tissue. The knowledge of the quantity of the above mentioned aminoacid, which is specific of collagen, is considered very important to define the nature of tissue present in Dupuytren's disease and to understand the metabolic defect. After a short bibliographic analysis of the matter, methods used for the examination of total oxyproline content (Kivirikko, 1967) are discussed. The result shows a marked increase of oxyproline proportionally to the pathological aspect of aponeurotical tissue of the hand. Two hypotheses are formulated: a) an increase of the proline-hydroxilase activity. b) a slow breakdown of collagen fibers.", "contents": "[Biochemical study of the human palmar aponeurosis under normal and pathological conditions]. Study of oxyproline content of the palmar aponeurosis connective tissue. The knowledge of the quantity of the above mentioned aminoacid, which is specific of collagen, is considered very important to define the nature of tissue present in Dupuytren's disease and to understand the metabolic defect. After a short bibliographic analysis of the matter, methods used for the examination of total oxyproline content (Kivirikko, 1967) are discussed. The result shows a marked increase of oxyproline proportionally to the pathological aspect of aponeurotical tissue of the hand. Two hypotheses are formulated: a) an increase of the proline-hydroxilase activity. b) a slow breakdown of collagen fibers."} {"id": "PMID:177137", "title": "[Immunocytochemical study of corticotropic cells in the adenohypophysis of the chick embryo].", "content": "Corticotrophin cells of the pituitary have been studied immunocytologically with I.S. anti-A.C.T.H. (1-24) and I.S. anti-A.C.T.H. (17-39). These sera show differentiated cells as soon as the 8th of incubation. These cells remain located within the anterior part of the adenohypophysis. They are not \"revelated\" by I.S. anti-beta-M.S.H. and I.S. anti-beta-LPH.", "contents": "[Immunocytochemical study of corticotropic cells in the adenohypophysis of the chick embryo]. Corticotrophin cells of the pituitary have been studied immunocytologically with I.S. anti-A.C.T.H. (1-24) and I.S. anti-A.C.T.H. (17-39). These sera show differentiated cells as soon as the 8th of incubation. These cells remain located within the anterior part of the adenohypophysis. They are not \"revelated\" by I.S. anti-beta-M.S.H. and I.S. anti-beta-LPH."} {"id": "PMID:177138", "title": "[Mechanism of the appearance of nuclear inclusions with microfilaments and microtubules in sympathetic neurons. Influence of dibutyryl-adenosine 3'-5' monophosphate and theophylline].", "content": "As we have shown previously the nucleus of sympathetic neurons contains microtubules and microfilaments giving rise to highly organized inclusions. Present in vivo experiments on cat stellate ganglia have shown that dibutyryl cyclic AMP and theophyllin induce an increase of their frequency (up to 8.5 fold). These and earlier observations lead us to conclude that cyclic AMP mediates the process of nuclear microtubules and microfilaments assembly from preformed protein subunits.", "contents": "[Mechanism of the appearance of nuclear inclusions with microfilaments and microtubules in sympathetic neurons. Influence of dibutyryl-adenosine 3'-5' monophosphate and theophylline]. As we have shown previously the nucleus of sympathetic neurons contains microtubules and microfilaments giving rise to highly organized inclusions. Present in vivo experiments on cat stellate ganglia have shown that dibutyryl cyclic AMP and theophyllin induce an increase of their frequency (up to 8.5 fold). These and earlier observations lead us to conclude that cyclic AMP mediates the process of nuclear microtubules and microfilaments assembly from preformed protein subunits."} {"id": "PMID:177145", "title": "The effect of premarin on blood loss attending open heart surgery.", "content": "Premarin was administered prophylactically to every other patient in a series of 148 consecutive cases of open intracardiac surgery. Of these, 132 patients were matched to analyse the results of Premarin administration and postoperative blood loss. There were 67 patients who were given Premarin and 65 who did not receive this drug; both groups were identical in respect of age and sex. Matching was undertaken according to history of previous cardiac operations and anticoagulation, type of valve surgery or repair of congenital anomaly, duration of perfusion, platelet count and the use of fresh blood and epsilon-aminocaproic acid in the postoperative period. The prophylactic use of Premarin was not associated with a reduction in postoperative bleeding.", "contents": "The effect of premarin on blood loss attending open heart surgery. Premarin was administered prophylactically to every other patient in a series of 148 consecutive cases of open intracardiac surgery. Of these, 132 patients were matched to analyse the results of Premarin administration and postoperative blood loss. There were 67 patients who were given Premarin and 65 who did not receive this drug; both groups were identical in respect of age and sex. Matching was undertaken according to history of previous cardiac operations and anticoagulation, type of valve surgery or repair of congenital anomaly, duration of perfusion, platelet count and the use of fresh blood and epsilon-aminocaproic acid in the postoperative period. The prophylactic use of Premarin was not associated with a reduction in postoperative bleeding."} {"id": "PMID:177146", "title": "Malignant acanthosis nigricans and its unusual association with carcinoma of the colon and carcinoma of the cervix.", "content": "Malignant acanthosis nigricans is rarely associated with carcinoma of the bowel or cervix. However, this dermatosis is described in a case of adenocarcinoma of the ascending colon, and in another with carcinoma of the cervix.", "contents": "Malignant acanthosis nigricans and its unusual association with carcinoma of the colon and carcinoma of the cervix. Malignant acanthosis nigricans is rarely associated with carcinoma of the bowel or cervix. However, this dermatosis is described in a case of adenocarcinoma of the ascending colon, and in another with carcinoma of the cervix."} {"id": "PMID:177152", "title": "The effects of long term feeding of Solanum glaucophyllum to growing rats on Ca, Mg, P and bone metabolism.", "content": "The effects of the long term ingestion of Solanum Glaucophyllum leaves (SG) by the rat was investigated in two series of experiments; the animals were fed a normal (for 8 weeks) or a low Ca diet (for 5 weeks). With both diets, the intestinal absorption of Ca was increased and the endogenous fecal Ca excretion was decreased by SG treatment. Added to a normal Ca diet, SG increased the urinary excretion of Ca, Mg and P and reduced the excretion of hydroxyproline and pyrophosphate. At the histological level, SG induced a higher rate of bone tissue synthesis on trabecular and endosteal surfaces. The bone content of hydroxyproline and citrate increased significantly. The total alkaline phosphatase activity of plasma decreased as a function of SG intake due to a decreased in the activity of the intestinal isoenzyme, which was not compensated by the increase in the bone isoenzyme activity. The Mg absorption was decreased by SG inducing lower Mg balances and lower plasma Mg levels. Added to a low Ca diet, SG increased the severity of the secondary hyperparathyroidism induced by the diet. The urinary excretion of hydroxyproline and the plasma alkaline phosphatase activity (both isoenzymes) were significantly increased. The Na and K content of bone decreased as a function of SG intake. 45Ca kinetic experiments revealed that SG increased the rate of Ca resorption and the rate constant of the fast exchangeable Ca pool, in both diets.", "contents": "The effects of long term feeding of Solanum glaucophyllum to growing rats on Ca, Mg, P and bone metabolism. The effects of the long term ingestion of Solanum Glaucophyllum leaves (SG) by the rat was investigated in two series of experiments; the animals were fed a normal (for 8 weeks) or a low Ca diet (for 5 weeks). With both diets, the intestinal absorption of Ca was increased and the endogenous fecal Ca excretion was decreased by SG treatment. Added to a normal Ca diet, SG increased the urinary excretion of Ca, Mg and P and reduced the excretion of hydroxyproline and pyrophosphate. At the histological level, SG induced a higher rate of bone tissue synthesis on trabecular and endosteal surfaces. The bone content of hydroxyproline and citrate increased significantly. The total alkaline phosphatase activity of plasma decreased as a function of SG intake due to a decreased in the activity of the intestinal isoenzyme, which was not compensated by the increase in the bone isoenzyme activity. The Mg absorption was decreased by SG inducing lower Mg balances and lower plasma Mg levels. Added to a low Ca diet, SG increased the severity of the secondary hyperparathyroidism induced by the diet. The urinary excretion of hydroxyproline and the plasma alkaline phosphatase activity (both isoenzymes) were significantly increased. The Na and K content of bone decreased as a function of SG intake. 45Ca kinetic experiments revealed that SG increased the rate of Ca resorption and the rate constant of the fast exchangeable Ca pool, in both diets."} {"id": "PMID:177153", "title": "Osteoclast ultrastructure in Paget's disease.", "content": "The ultrastructural study of osteoclasts in biopsies from 12 patients with Paget's disease reveals several cytological anomalies. In Particular, nuclear inclusions, consisting essentially of striated filaments about 150 A in diameter, often organized in bundles and sometimes in paracrystalline arrays, appear to be specific to the disease. Morphologically, the inclusions are remarkably similar to those observed in various cases of viral attack, and the hypothesis of the action of a possible external agent in Paget's disease cannot be ruled out.", "contents": "Osteoclast ultrastructure in Paget's disease. The ultrastructural study of osteoclasts in biopsies from 12 patients with Paget's disease reveals several cytological anomalies. In Particular, nuclear inclusions, consisting essentially of striated filaments about 150 A in diameter, often organized in bundles and sometimes in paracrystalline arrays, appear to be specific to the disease. Morphologically, the inclusions are remarkably similar to those observed in various cases of viral attack, and the hypothesis of the action of a possible external agent in Paget's disease cannot be ruled out."} {"id": "PMID:177154", "title": "Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.", "content": "Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.", "contents": "Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man. Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone."} {"id": "PMID:177155", "title": "Perturbation of lecithin bilayer structure by globoside.", "content": "The ultrastructure of aggregates formed by mixtures of pig erythrocyte lecithin, cholesterol and globoside in aqueous systems was studied by electron microscopy and X-ray diffraction. Globoside and lecithin in up to equimolar amounts formed a lamellar mesophase, although the structure of the lamellae was perturbed. Mixtures containing excess globoside formed complex tubular or reticular aggregates. Cholesterol appeared to promote mixing of lecithin and globoside. The flexibility gradient of the hydrocarbon (hc) region of the lipid bilayers was studied using electron spin resonance (esr) spectroscopy of various nitroxide-labelled stearic acid probes. Globoside in equimolar amounts greatly perturbed the order parameters of lecithin bilayers, reducing the fluidity of the hc region and flattening the flexibility gradient near the polar (p) surface. The effect of globoside on lecithin-cholesterol bilayers was not so pronounced, since the latter was already more ordered than lecithin bilayers. A phase transition of pure globoside at 55 degrees C, involving 'melting' of the hc chains was also detected using X-ray and esr spectroscopic techniques. The interbilayer spacing, dw, of equimolar lecithin-globoside lamellar phase increased by 42% from that of lecithin bilayers, indicating that the glycolipid p group may increase the net repulsive force between bilayers, as was previously predicted theoretically.", "contents": "Perturbation of lecithin bilayer structure by globoside. The ultrastructure of aggregates formed by mixtures of pig erythrocyte lecithin, cholesterol and globoside in aqueous systems was studied by electron microscopy and X-ray diffraction. Globoside and lecithin in up to equimolar amounts formed a lamellar mesophase, although the structure of the lamellae was perturbed. Mixtures containing excess globoside formed complex tubular or reticular aggregates. Cholesterol appeared to promote mixing of lecithin and globoside. The flexibility gradient of the hydrocarbon (hc) region of the lipid bilayers was studied using electron spin resonance (esr) spectroscopy of various nitroxide-labelled stearic acid probes. Globoside in equimolar amounts greatly perturbed the order parameters of lecithin bilayers, reducing the fluidity of the hc region and flattening the flexibility gradient near the polar (p) surface. The effect of globoside on lecithin-cholesterol bilayers was not so pronounced, since the latter was already more ordered than lecithin bilayers. A phase transition of pure globoside at 55 degrees C, involving 'melting' of the hc chains was also detected using X-ray and esr spectroscopic techniques. The interbilayer spacing, dw, of equimolar lecithin-globoside lamellar phase increased by 42% from that of lecithin bilayers, indicating that the glycolipid p group may increase the net repulsive force between bilayers, as was previously predicted theoretically."} {"id": "PMID:177156", "title": "Low-affinity interaction of ethanol with the fluorescent complex between horse liver alcohol dehydrogenase and auramine O.", "content": "Quenching of the fluorescence of the complex between horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase (EC 1.1.1.1) and auramine O complex is inconsistent with a simple competitive displacement of auramine O by ethanol. Instead, the action of ethanol requires an explanation in terms of a solvent effect, or the formation of an enzyme-auramine O-ethanol ternary complex. The latter complex would have to be the low-affinity variety similar to the enzyme-NADH-ethanol ternary complex encountered in the kinetic system.", "contents": "Low-affinity interaction of ethanol with the fluorescent complex between horse liver alcohol dehydrogenase and auramine O. Quenching of the fluorescence of the complex between horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase (EC 1.1.1.1) and auramine O complex is inconsistent with a simple competitive displacement of auramine O by ethanol. Instead, the action of ethanol requires an explanation in terms of a solvent effect, or the formation of an enzyme-auramine O-ethanol ternary complex. The latter complex would have to be the low-affinity variety similar to the enzyme-NADH-ethanol ternary complex encountered in the kinetic system."} {"id": "PMID:177157", "title": "Effect of various sterols on the 22Na permeability and fluidity of phospholipid bilayer membranes.", "content": "Sodium-22 efflux was measured in multilamellar liposomes composed of egg lecithin, dicetylphosphate, and various sterols. In a parallel series of experiments a spin labelled fatty acid ester was incorporated into similar vesicles and the molecular motion of the spin label monitored by electron spin resonance spectroscopy. Spin lable mobility was used as a measure of phospholipid hydrocarbon chain motion. There was a poor correlation between the effects of these sterols on sodium permeability and their effects on the motion of the lipid chains. It is postulated that sterols alter sodium transport not only through a reduction in the motional freedom of membrane lipids, but also through changes in the partitioning of sodium between membrane and aqueous phases.", "contents": "Effect of various sterols on the 22Na permeability and fluidity of phospholipid bilayer membranes. Sodium-22 efflux was measured in multilamellar liposomes composed of egg lecithin, dicetylphosphate, and various sterols. In a parallel series of experiments a spin labelled fatty acid ester was incorporated into similar vesicles and the molecular motion of the spin label monitored by electron spin resonance spectroscopy. Spin lable mobility was used as a measure of phospholipid hydrocarbon chain motion. There was a poor correlation between the effects of these sterols on sodium permeability and their effects on the motion of the lipid chains. It is postulated that sterols alter sodium transport not only through a reduction in the motional freedom of membrane lipids, but also through changes in the partitioning of sodium between membrane and aqueous phases."} {"id": "PMID:177158", "title": "Inhibition of choline transport into human erythrocytes by choline mustard aziridinium ion.", "content": "Acetylcholine mustard aziridinium ion inhibited the transport of [3H]choline into human erythrocytes. Treatment of the erythrocytes with 1 X 10(-4) M tetraethylpyrophosphate prevented the inhibition of [3H]choline transport by acetylcholine mustard aziridinium ion. Hydrolyzed acetylcholine mustard aziridinium ion inhibited choline transport both in the presence and absence of 1 X 10(-4) M tetraethylpyrophosphate. The product of hydrolysis was equipotent with acetylcholine mustard in its ability to inhibit choline transport; incubation of this product with sodium thiosulfate prevented inhibition of choline transport thereby indicating the presence of an aziridinium ion. The hydrolysis product is likely to be choline mustard aziridinium ion. Results on the efflux of [3H]choline from erythrocytes in the presence of the proposed choline mustard aziridinium ion showed that the mustard moiety was transported into the red cells on the choline carrier. The rate of efflux of [3H]choline produced by choline mustard aziridinium ion was 55% of that produced by the same concentration of choline. It is concluded that acetylcholinesterase (EC 3.1.1.7) of red cells rapidly hydrolyzes acetylcholine mustard aziridinium ion to acetate and choline mustard aziridinium and the latter compound can act as a potent inhibitor of choline transport. This finding would indicate that the hemicholinium-like toxicity of acetylcholine mustard in the mouse is due to the formation of choline mustard aziridinium ion.", "contents": "Inhibition of choline transport into human erythrocytes by choline mustard aziridinium ion. Acetylcholine mustard aziridinium ion inhibited the transport of [3H]choline into human erythrocytes. Treatment of the erythrocytes with 1 X 10(-4) M tetraethylpyrophosphate prevented the inhibition of [3H]choline transport by acetylcholine mustard aziridinium ion. Hydrolyzed acetylcholine mustard aziridinium ion inhibited choline transport both in the presence and absence of 1 X 10(-4) M tetraethylpyrophosphate. The product of hydrolysis was equipotent with acetylcholine mustard in its ability to inhibit choline transport; incubation of this product with sodium thiosulfate prevented inhibition of choline transport thereby indicating the presence of an aziridinium ion. The hydrolysis product is likely to be choline mustard aziridinium ion. Results on the efflux of [3H]choline from erythrocytes in the presence of the proposed choline mustard aziridinium ion showed that the mustard moiety was transported into the red cells on the choline carrier. The rate of efflux of [3H]choline produced by choline mustard aziridinium ion was 55% of that produced by the same concentration of choline. It is concluded that acetylcholinesterase (EC 3.1.1.7) of red cells rapidly hydrolyzes acetylcholine mustard aziridinium ion to acetate and choline mustard aziridinium and the latter compound can act as a potent inhibitor of choline transport. This finding would indicate that the hemicholinium-like toxicity of acetylcholine mustard in the mouse is due to the formation of choline mustard aziridinium ion."} {"id": "PMID:177159", "title": "Monolayer cultures of dispersed cells from bovine anterior pituitary: responses to synthetic hypophysiotropic peptides.", "content": "Cells were dispersed from bovine anterior pituitary glands, by digestion with collagenase, and cultured. After 4 days the cell monolayers were incubated with fresh medium containing synthetic hypophysiotropic peptides for 2, 6, or 20 h, and hormone released into the medium was estimated by radioimmunoassay. After 2 h, thyroid releasing hormone (TRH) stimulated the release of thyroid-stimulating hormone (TSH) up to eightfold, and of prolactin (PRL) and follicle-stimulating hormone (FSH) about twofold at a minimal effective concentration of 1 ng/ml; enhanced growth hormone (GH) release was not apparent until 20 h, and release of luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) was unaffected. Luteinizing hormone releasing hormone (LH-RH) enhanced release of LH maximally (three- to fourfold) during a 2 h incubation and was effective at 0.1 ng/ml; FSH release was significantly enhanced by about 50% above control level. Growth hormone release inhibiting hormone (GH-RIH)(somatostatin) showed significant effects only in the 20 h incubation; GH release was inhibited by 50% and release of PRL was slightly, but significantly, enhanced. Pituitary cell monolayers apparently permit maximal expression of releasing activities inherent in the hypothalamic hormones.", "contents": "Monolayer cultures of dispersed cells from bovine anterior pituitary: responses to synthetic hypophysiotropic peptides. Cells were dispersed from bovine anterior pituitary glands, by digestion with collagenase, and cultured. After 4 days the cell monolayers were incubated with fresh medium containing synthetic hypophysiotropic peptides for 2, 6, or 20 h, and hormone released into the medium was estimated by radioimmunoassay. After 2 h, thyroid releasing hormone (TRH) stimulated the release of thyroid-stimulating hormone (TSH) up to eightfold, and of prolactin (PRL) and follicle-stimulating hormone (FSH) about twofold at a minimal effective concentration of 1 ng/ml; enhanced growth hormone (GH) release was not apparent until 20 h, and release of luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) was unaffected. Luteinizing hormone releasing hormone (LH-RH) enhanced release of LH maximally (three- to fourfold) during a 2 h incubation and was effective at 0.1 ng/ml; FSH release was significantly enhanced by about 50% above control level. Growth hormone release inhibiting hormone (GH-RIH)(somatostatin) showed significant effects only in the 20 h incubation; GH release was inhibited by 50% and release of PRL was slightly, but significantly, enhanced. Pituitary cell monolayers apparently permit maximal expression of releasing activities inherent in the hypothalamic hormones."} {"id": "PMID:177160", "title": "Effects of potassium chloride and smooth muscle relaxants on tension and cyclic nucleotide levels in rat myometrium.", "content": "Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP) were decreased by 40%. At this point both nitroglycerin (4 X 10(-4) M) and papaverine (2 X 10(-5) M) were capable of relaxing the depolarized muscles without significantly increasing cyclic AMP levels. Isoproterenol, in concentrations from 5 X 10(-9) M to 10(-6) M, relaxed the depolarized muscles and significantly increased tissue levels of cyclic AMP. However, the magnitudes of the cyclic AMP increases seen after the lower concentrations of isoproterenol were small relative to the increases observed during KCl-contracture alone. For example, the 40% elevation of cyclic AMP seen 10 min after KCl-depolarization did not cause the muscles to relax, whereas 5 X 10(-9) M isoproterenol caused relaxation with an increase in cyclic AMP levels of only 16% over depolarized controls. It was concluded that changes in total tissue levels of cyclic AMP were not responsible for the uterine relaxation caused by nitroglycerin, papaverine or isoproterenol in these experiments. Cyclic GMP levels in the depolarized muscles were not significantly changed by isoproterenol or papaverine but were increased approximately 80% by nitroglycerin. The above results are not consistent with the previously suggested roles for cyclic GMP and cyclic AMP as mediators of smooth muscle contraction and relaxation, respectively.", "contents": "Effects of potassium chloride and smooth muscle relaxants on tension and cyclic nucleotide levels in rat myometrium. Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP) were decreased by 40%. At this point both nitroglycerin (4 X 10(-4) M) and papaverine (2 X 10(-5) M) were capable of relaxing the depolarized muscles without significantly increasing cyclic AMP levels. Isoproterenol, in concentrations from 5 X 10(-9) M to 10(-6) M, relaxed the depolarized muscles and significantly increased tissue levels of cyclic AMP. However, the magnitudes of the cyclic AMP increases seen after the lower concentrations of isoproterenol were small relative to the increases observed during KCl-contracture alone. For example, the 40% elevation of cyclic AMP seen 10 min after KCl-depolarization did not cause the muscles to relax, whereas 5 X 10(-9) M isoproterenol caused relaxation with an increase in cyclic AMP levels of only 16% over depolarized controls. It was concluded that changes in total tissue levels of cyclic AMP were not responsible for the uterine relaxation caused by nitroglycerin, papaverine or isoproterenol in these experiments. Cyclic GMP levels in the depolarized muscles were not significantly changed by isoproterenol or papaverine but were increased approximately 80% by nitroglycerin. The above results are not consistent with the previously suggested roles for cyclic GMP and cyclic AMP as mediators of smooth muscle contraction and relaxation, respectively."} {"id": "PMID:177161", "title": "On the specificity of histamine H2-receptor antagonists in the rat cerebral cortex.", "content": "The effects of iontophoretically applied histamine H2-receptor antagonists and their antagonism of various amines, acetylcholine (ACh), and adenosine 5'-monophosphate (5'-AMP) were studied on spontaneously active rat cerebral cortical neurons. Metiamide selectively blocked the depressant actions of histamine. Burimamide, in amounts necessary for histamine antagonism, also antagonized the depressant effects of noradrenaline, dopamine, and 5-hydroxytryptamine. Neither antagonist affected 5'-AMP-induced depressions, but both reduced or blocked the excitatory actions of ACh. It is concluded that metiamide may be useful as a reliable antagonist of H2 receptors on cerebral cortical neurons.", "contents": "On the specificity of histamine H2-receptor antagonists in the rat cerebral cortex. The effects of iontophoretically applied histamine H2-receptor antagonists and their antagonism of various amines, acetylcholine (ACh), and adenosine 5'-monophosphate (5'-AMP) were studied on spontaneously active rat cerebral cortical neurons. Metiamide selectively blocked the depressant actions of histamine. Burimamide, in amounts necessary for histamine antagonism, also antagonized the depressant effects of noradrenaline, dopamine, and 5-hydroxytryptamine. Neither antagonist affected 5'-AMP-induced depressions, but both reduced or blocked the excitatory actions of ACh. It is concluded that metiamide may be useful as a reliable antagonist of H2 receptors on cerebral cortical neurons."} {"id": "PMID:177162", "title": "Quantitative aspects of cyclic AMP and relaxation in the rabbit anterior mesenteric-portal vein.", "content": "Rabbit anterior mesenteric-portal vein was shown to exhibit a positive correlation between relaxation and cyclic AMP levels using different concentrations of isoproterenol for varying exposure times. No consistent relationship was found between cyclic AMP and relaxation using a series of phosphodiesterase inhibitors (papaverine, SC2964, or RA233). In sodium-free (Tris-substituted) Kreb's solution, the addition of isoproterenol still increased cyclic AMP levels, but there was no relaxation. Dibutyryl cyclic AMP was also ineffective in sodium-free solution. Under identical conditions, both relaxation and increases in cyclic AMP produced by papaverine and SC2964 were found to be independent of extracellular sodium. We conclude, therefore, that increased cyclic AMP may be involved in isoproterenol-induced relaxation possibly acting via increased Na+-Ca2+ exchange, but plays only a small role, if any, in smooth muscle relaxation produced by papaverine, RA233, or SC2964.", "contents": "Quantitative aspects of cyclic AMP and relaxation in the rabbit anterior mesenteric-portal vein. Rabbit anterior mesenteric-portal vein was shown to exhibit a positive correlation between relaxation and cyclic AMP levels using different concentrations of isoproterenol for varying exposure times. No consistent relationship was found between cyclic AMP and relaxation using a series of phosphodiesterase inhibitors (papaverine, SC2964, or RA233). In sodium-free (Tris-substituted) Kreb's solution, the addition of isoproterenol still increased cyclic AMP levels, but there was no relaxation. Dibutyryl cyclic AMP was also ineffective in sodium-free solution. Under identical conditions, both relaxation and increases in cyclic AMP produced by papaverine and SC2964 were found to be independent of extracellular sodium. We conclude, therefore, that increased cyclic AMP may be involved in isoproterenol-induced relaxation possibly acting via increased Na+-Ca2+ exchange, but plays only a small role, if any, in smooth muscle relaxation produced by papaverine, RA233, or SC2964."} {"id": "PMID:177163", "title": "Comparative ultrastructure of selected oral streptococci: thin-sectioning and freeze-etching studies.", "content": "The ultrastructure of Streptococcus mutans, serotypes a-e, S. sanguis, S. mitis, and S. salivarius HHT, were examined by the techniques of thin-sectioning and freeze-etching. The cell walls varied in width between 15 and 46 nm and were covered with an electron-dense fibrillar or fuzz layer. The cytoplasmic membrane was in close association with numerous mesosomes which were, in turn, either closely associated or in contact with the bacterial chromosome. In freeze-etch replicas, the outermost layer of the cell wall was fibrous, and the cytoplasmic membrane was covered with particles composed of several subunits. Both particle-clusters and particle-free areas occurred on the surfaces of the cytoplasmic membrane, as well as a crystalline array in the ground plasm of the cell.", "contents": "Comparative ultrastructure of selected oral streptococci: thin-sectioning and freeze-etching studies. The ultrastructure of Streptococcus mutans, serotypes a-e, S. sanguis, S. mitis, and S. salivarius HHT, were examined by the techniques of thin-sectioning and freeze-etching. The cell walls varied in width between 15 and 46 nm and were covered with an electron-dense fibrillar or fuzz layer. The cytoplasmic membrane was in close association with numerous mesosomes which were, in turn, either closely associated or in contact with the bacterial chromosome. In freeze-etch replicas, the outermost layer of the cell wall was fibrous, and the cytoplasmic membrane was covered with particles composed of several subunits. Both particle-clusters and particle-free areas occurred on the surfaces of the cytoplasmic membrane, as well as a crystalline array in the ground plasm of the cell."} {"id": "PMID:177167", "title": "Anaplastic carcinoma of the esophagus. Report of three cases and their histogenetic consideration.", "content": "The autopsies of three cases of esophageal anaplastic carcinoma with an oat cell pattern are presented. Grossly, each case revealed a fungating growth and showed extensive metastases all over the body. The histology bears a striking resemblance to that of oat cell carcinoma of the lung, occasionally showing rosette formation, mucin secretion, and intracytoplasmic argyrophil granules in each case. These peculiar carcinomas most probably were derived from the esophageal submucosal glands. They were composed of both a cell group of argyrophil variety and a group of mucus-secreting variety which may have originated from the more primitive cells capable of differentiation into either variety.", "contents": "Anaplastic carcinoma of the esophagus. Report of three cases and their histogenetic consideration. The autopsies of three cases of esophageal anaplastic carcinoma with an oat cell pattern are presented. Grossly, each case revealed a fungating growth and showed extensive metastases all over the body. The histology bears a striking resemblance to that of oat cell carcinoma of the lung, occasionally showing rosette formation, mucin secretion, and intracytoplasmic argyrophil granules in each case. These peculiar carcinomas most probably were derived from the esophageal submucosal glands. They were composed of both a cell group of argyrophil variety and a group of mucus-secreting variety which may have originated from the more primitive cells capable of differentiation into either variety."} {"id": "PMID:177168", "title": "Pulmonary tumorlet. A form of peripheral carcinoid.", "content": "Twenty cases of pulmonary tumorlet are presented. Approximately one-third of the tumors occurred in lungs severely scarred by bronchiectasis or other inflammatory processes; the other two-thirds were found in lungs with little to no scarring. In the former instances, tumorlets were found in large scars in which identifying architectural features had been destroyed. In the latter, the tumorlets were seen in minute fibrous nodules, surrounding or obliterating small bronchi or bronchioles. Argyrophilic granules were demonstrated in 14 of 15 cases; in the electron microscope these were consistent with neurosecretory granules. Their location, silver staining properties, and ultrastructure suggest that pulmonary tumorlets are minute peripheral carcinoid tumors.", "contents": "Pulmonary tumorlet. A form of peripheral carcinoid. Twenty cases of pulmonary tumorlet are presented. Approximately one-third of the tumors occurred in lungs severely scarred by bronchiectasis or other inflammatory processes; the other two-thirds were found in lungs with little to no scarring. In the former instances, tumorlets were found in large scars in which identifying architectural features had been destroyed. In the latter, the tumorlets were seen in minute fibrous nodules, surrounding or obliterating small bronchi or bronchioles. Argyrophilic granules were demonstrated in 14 of 15 cases; in the electron microscope these were consistent with neurosecretory granules. Their location, silver staining properties, and ultrastructure suggest that pulmonary tumorlets are minute peripheral carcinoid tumors."} {"id": "PMID:177169", "title": "Primary intracranial Burkitt's lymphoma in an infant.", "content": "A case of intracranial Burkitt's lymphoma is reported in a child whose symptoms began at 3 months of age with a definite histologic diagnosis established at 18 months. Serologic studies demonstrated high antibody titers to Epstein-Barr virus (EBV) in the patient and in four out of five members of the immediate family. The patient also demonstrated immunity to antigens derived from African Burkitt's lymphoma cell lines. The autopsy findings strongly support the case for the primary intracranial origin of the neoplasm and a perinatal infection with EBV is probable in this case.", "contents": "Primary intracranial Burkitt's lymphoma in an infant. A case of intracranial Burkitt's lymphoma is reported in a child whose symptoms began at 3 months of age with a definite histologic diagnosis established at 18 months. Serologic studies demonstrated high antibody titers to Epstein-Barr virus (EBV) in the patient and in four out of five members of the immediate family. The patient also demonstrated immunity to antigens derived from African Burkitt's lymphoma cell lines. The autopsy findings strongly support the case for the primary intracranial origin of the neoplasm and a perinatal infection with EBV is probable in this case."} {"id": "PMID:177170", "title": "Wilms' tumor in adolescence.", "content": "Two cases of Wilms' tumor in adolescent males are presented. The clinical and radiographic findings were unusual and both presented atypical gross and microscopic features that could be correlated with the radiographic findings. Histologic examination of both tumors showed evidence of tubular and glomerular maturation, a feature usually associated with Wilms' tumors of early infancy. One of the tumors contained a large amount of cartilage and bone. The other was grossly cystic and incorporated some features of multilocular cystadenoma, a benign metanephric tumor.", "contents": "Wilms' tumor in adolescence. Two cases of Wilms' tumor in adolescent males are presented. The clinical and radiographic findings were unusual and both presented atypical gross and microscopic features that could be correlated with the radiographic findings. Histologic examination of both tumors showed evidence of tubular and glomerular maturation, a feature usually associated with Wilms' tumors of early infancy. One of the tumors contained a large amount of cartilage and bone. The other was grossly cystic and incorporated some features of multilocular cystadenoma, a benign metanephric tumor."} {"id": "PMID:177171", "title": "Glioblastoma multiforme with extraneural metastases in the absence of previous surgery.", "content": "A 63-year-old man was found to have an intracerebral glioblastoma multiforme and preoperative roentgenographic evidence of a mass in the middle lobe of the right lung. Because of the rarity of extraneural metastases from glioblastoma, especially in the absence of prior surgery, the lesions were considered to be separate neoplasms until death. The histologic appearance of the lung tumor obtained at autopsy was identical to the cerebral tumor. Additional metastases were found to bronchial lymph nodes and a lumbar vertebra. This case demonstrates that a glioblastoma can spontaneously metastasize extraneurally. Invasion of the glioblastoma into the lumen of a blood vessel was demonstrated within the primary tumor. Embolization of cells to the lung and beyond is the suspected mode of spread.", "contents": "Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. A 63-year-old man was found to have an intracerebral glioblastoma multiforme and preoperative roentgenographic evidence of a mass in the middle lobe of the right lung. Because of the rarity of extraneural metastases from glioblastoma, especially in the absence of prior surgery, the lesions were considered to be separate neoplasms until death. The histologic appearance of the lung tumor obtained at autopsy was identical to the cerebral tumor. Additional metastases were found to bronchial lymph nodes and a lumbar vertebra. This case demonstrates that a glioblastoma can spontaneously metastasize extraneurally. Invasion of the glioblastoma into the lumen of a blood vessel was demonstrated within the primary tumor. Embolization of cells to the lung and beyond is the suspected mode of spread."} {"id": "PMID:177172", "title": "Inflammatory fibrous histiocytoma. An aggressive and lethal lesion.", "content": "During an investigation of soft tissue fibrohistiocytic tumors, seven cases were found which we believe represent a new and specific diagnostic subgroup of fibrous histiocytomas. All patients were adults (mean 52.6 years), only one of whom was younger than age 40. There were four females and three males; all were Caucasian. The tumors which occurred in the retroperitoneum, anterior chest wall, anterior abdominal wall, femoral area, and oral cavity, were large, averaging 8.5 cm., and although appearing encapsulated, were microscopically infiltrative. The common histologic feature of all cases was a diffuse and at times intense neutrophilic infiltrate unassociated with tissue necrosis, in combination with bland and anaplastic appearing histiocytes. The presence of this acute exudative reaction is a unique feature of these lesions, and was present not only in the original tumors, but in recurrences and metastatic foci as well. Other cell types including foam cells, lymphocytes, plasma cells, eosinophils, Reed-Sternberg-like and ganglion-like cells were commonly present. A storiform fibrous pattern, a hallmark of the fibrous histiocytomas was seen at some time in all but one case. The treacherous aspect of these lesions was their bland initial histologic appearance. The foci of foam cells associated with the inflammatory elements often led to a diagnosis of a benign inflammatory reaction or xanthogranuloma. However, follow-up has confirmed the aggressive and neoplastic nature of these lesions. The clinical course was usually protracted with multiple recurrences and eventual metastases. All patients died of their tumor, the average survival being 53 months; four patients survived over 5 years. At this time, we propose the term inflammatory fibrous histiocytoma to designate these lesions.", "contents": "Inflammatory fibrous histiocytoma. An aggressive and lethal lesion. During an investigation of soft tissue fibrohistiocytic tumors, seven cases were found which we believe represent a new and specific diagnostic subgroup of fibrous histiocytomas. All patients were adults (mean 52.6 years), only one of whom was younger than age 40. There were four females and three males; all were Caucasian. The tumors which occurred in the retroperitoneum, anterior chest wall, anterior abdominal wall, femoral area, and oral cavity, were large, averaging 8.5 cm., and although appearing encapsulated, were microscopically infiltrative. The common histologic feature of all cases was a diffuse and at times intense neutrophilic infiltrate unassociated with tissue necrosis, in combination with bland and anaplastic appearing histiocytes. The presence of this acute exudative reaction is a unique feature of these lesions, and was present not only in the original tumors, but in recurrences and metastatic foci as well. Other cell types including foam cells, lymphocytes, plasma cells, eosinophils, Reed-Sternberg-like and ganglion-like cells were commonly present. A storiform fibrous pattern, a hallmark of the fibrous histiocytomas was seen at some time in all but one case. The treacherous aspect of these lesions was their bland initial histologic appearance. The foci of foam cells associated with the inflammatory elements often led to a diagnosis of a benign inflammatory reaction or xanthogranuloma. However, follow-up has confirmed the aggressive and neoplastic nature of these lesions. The clinical course was usually protracted with multiple recurrences and eventual metastases. All patients died of their tumor, the average survival being 53 months; four patients survived over 5 years. At this time, we propose the term inflammatory fibrous histiocytoma to designate these lesions."} {"id": "PMID:177173", "title": "Morphologic study of virus-like particles in a case of acute leukemia.", "content": "Virus-like particles, grouped in clusters not bound by a membraine, were seen in electron micrographs of fresh leucoblasts of an acute leukemic patient. They consisted of large (100-nm diameter), round particles apparently composed of subunits. Tubular structures (30-50-nm diameter) were also seen in leucoblasts of the same patient. The two types of structures were never seen simultaneously in the same cell. The authors review the literature pertaining to the morphology of virus-like particles associated with malignant hematologic disease.", "contents": "Morphologic study of virus-like particles in a case of acute leukemia. Virus-like particles, grouped in clusters not bound by a membraine, were seen in electron micrographs of fresh leucoblasts of an acute leukemic patient. They consisted of large (100-nm diameter), round particles apparently composed of subunits. Tubular structures (30-50-nm diameter) were also seen in leucoblasts of the same patient. The two types of structures were never seen simultaneously in the same cell. The authors review the literature pertaining to the morphology of virus-like particles associated with malignant hematologic disease."} {"id": "PMID:177174", "title": "M\u00fcllerian adenosarcoma of the uterine cervix with heterologous elements: a light and electron microscopic study.", "content": "A m\u00fcllerian adenosarcoma with heterologous elements having the gross appearance of a sarcoma botryoides occurred in the uterine cervix of a 14-year-old girl. Histologically, the tumor was composed of an admixture of benign-appearing glands and a sarcomatous stroma, the latter containing areas of undifferentiated sarcoma and endometrial stromal sarcoma, as well as heterologous elements consisting of rhabdomyosarcoma and hyaline cartilage. No malignant epithelial component was observed. The distribution of benign m\u00fcllerian-type glands throughout the tumor simulated a malignant mixed m\u00fcllerian tumor in appearance. Ultrastructural studies of the stromal elements of the neoplasm suggest origin from primitive m\u00fcllerian stroma, and the glands have features of primitive m\u00fcllerian epithelium. This study supports the concept that the malignant mixed m\u00fcllerian tumor and related m\u00fcllerian sarcomas originate from a common undifferentiated multipotential m\u00fcllerian stem cell.", "contents": "M\u00fcllerian adenosarcoma of the uterine cervix with heterologous elements: a light and electron microscopic study. A m\u00fcllerian adenosarcoma with heterologous elements having the gross appearance of a sarcoma botryoides occurred in the uterine cervix of a 14-year-old girl. Histologically, the tumor was composed of an admixture of benign-appearing glands and a sarcomatous stroma, the latter containing areas of undifferentiated sarcoma and endometrial stromal sarcoma, as well as heterologous elements consisting of rhabdomyosarcoma and hyaline cartilage. No malignant epithelial component was observed. The distribution of benign m\u00fcllerian-type glands throughout the tumor simulated a malignant mixed m\u00fcllerian tumor in appearance. Ultrastructural studies of the stromal elements of the neoplasm suggest origin from primitive m\u00fcllerian stroma, and the glands have features of primitive m\u00fcllerian epithelium. This study supports the concept that the malignant mixed m\u00fcllerian tumor and related m\u00fcllerian sarcomas originate from a common undifferentiated multipotential m\u00fcllerian stem cell."} {"id": "PMID:177175", "title": "Metastatic cystosarcoma phyllodes: a light and electron microscopic study.", "content": "Two cases of metastatic cystosarcoma phyllodes, one in lung and the other in axillary lymph nodes, were studied with the light and the electron microscopes. The malignant element of these tumors appears to be a poorly differentiated mesenchymal cell. No evidence supporting the presence of epithelial cells was found. The tumor metastatic to the axilla exhibited intracellular virus-like particles similar to those described in adenocarcinoma of breast and other sarcomas.", "contents": "Metastatic cystosarcoma phyllodes: a light and electron microscopic study. Two cases of metastatic cystosarcoma phyllodes, one in lung and the other in axillary lymph nodes, were studied with the light and the electron microscopes. The malignant element of these tumors appears to be a poorly differentiated mesenchymal cell. No evidence supporting the presence of epithelial cells was found. The tumor metastatic to the axilla exhibited intracellular virus-like particles similar to those described in adenocarcinoma of breast and other sarcomas."} {"id": "PMID:177176", "title": "So-called \"minute pulmonary chemodectoma\": a tumor not related to paragangliomas.", "content": "Twenty-six cases of so-called \"minute pulmonary chemodectoma\" are presented. The patient population showed a marked female preponderance, and there appeared to be an association of the lesion with pulmonary injury from a variety of causes including cardiac failure, chronic bronchitis and emphysema, and thromboemboli. Half the cases had multiple tumors. Microscopically, the tumors consisted of nests of cells in the interstitial tissue near small veins. Argentaffin and argyrophil stains failed to demonstrate cytoplasmic granules in any case. By electron microscopy, the nests were composed of large cells with broadly interdigitating processes connected by many well-formed desmosomes. The cytoplasm was filled with numerous 60-A filaments. The Golgi apparatus was prominent, while other organelles were sparse. No secretory granules were identified. It is concluded that the fine structure and lack of silver-positive granules are inconsistent with the morphology of previously reported paragangliomas, but that there is a resemblance at the light and electron microscopic level to meningeal arachnoed cells and the cells of meningiomas.", "contents": "So-called \"minute pulmonary chemodectoma\": a tumor not related to paragangliomas. Twenty-six cases of so-called \"minute pulmonary chemodectoma\" are presented. The patient population showed a marked female preponderance, and there appeared to be an association of the lesion with pulmonary injury from a variety of causes including cardiac failure, chronic bronchitis and emphysema, and thromboemboli. Half the cases had multiple tumors. Microscopically, the tumors consisted of nests of cells in the interstitial tissue near small veins. Argentaffin and argyrophil stains failed to demonstrate cytoplasmic granules in any case. By electron microscopy, the nests were composed of large cells with broadly interdigitating processes connected by many well-formed desmosomes. The cytoplasm was filled with numerous 60-A filaments. The Golgi apparatus was prominent, while other organelles were sparse. No secretory granules were identified. It is concluded that the fine structure and lack of silver-positive granules are inconsistent with the morphology of previously reported paragangliomas, but that there is a resemblance at the light and electron microscopic level to meningeal arachnoed cells and the cells of meningiomas."} {"id": "PMID:177177", "title": "Multiple molecular forms of lactate dehydrogenase and glucose 6-phosphate dehydrogenase in normal and abnormal human breast tissues.", "content": "Normal and abnormal breast samples of women were analyzed for multiple molecular forms of lactate dehydrogenase and glucose 6-phosphate dehydrogenase, using acrylamide disc gel electrophoresis and specific enzyme staining techniques for separation and quantitation. Infiltrating ductal carcinomas demonstrated a significant increase (three to six-fold) in the proportion of LDH-5 compared to samples of normal breast, fibrocystic disease and fibroadenoma, indicative of a shift toward the muscle-type lactate dehydrogenase in neoplasia. For glucose 6-phosphate dehydrogenase, carcinomas were found to contain increased proportions of the fastest migrating species, G6PD-I. Total enzyme activity/mg DNA was elevated in meoplastic tissues. Little or no alteration in isoenzyme profiles could be related to menopausal status of the patient.", "contents": "Multiple molecular forms of lactate dehydrogenase and glucose 6-phosphate dehydrogenase in normal and abnormal human breast tissues. Normal and abnormal breast samples of women were analyzed for multiple molecular forms of lactate dehydrogenase and glucose 6-phosphate dehydrogenase, using acrylamide disc gel electrophoresis and specific enzyme staining techniques for separation and quantitation. Infiltrating ductal carcinomas demonstrated a significant increase (three to six-fold) in the proportion of LDH-5 compared to samples of normal breast, fibrocystic disease and fibroadenoma, indicative of a shift toward the muscle-type lactate dehydrogenase in neoplasia. For glucose 6-phosphate dehydrogenase, carcinomas were found to contain increased proportions of the fastest migrating species, G6PD-I. Total enzyme activity/mg DNA was elevated in meoplastic tissues. Little or no alteration in isoenzyme profiles could be related to menopausal status of the patient."} {"id": "PMID:177178", "title": "Small cell undifferentiated carcinoma of salivary gland origin: an ultrastructural study.", "content": "A case of small cell carcinoma of salivary gland was studied by light and electron microscopy. Light microscopy showed sheets of small uniform cells with scanty cytoplasm and pyknotic nuclei. Electron microscopy showed two distinct cell types; an electron-lucent epithelial-appearing cell, and a denser cell with processes containing bundles of filaments and other features suggesting myoepithelial differentiation. Neurosecretory granules were absent. These findings support a salivary duct origin, and are evidence against a neurendocrine derivation for this tumor.", "contents": "Small cell undifferentiated carcinoma of salivary gland origin: an ultrastructural study. A case of small cell carcinoma of salivary gland was studied by light and electron microscopy. Light microscopy showed sheets of small uniform cells with scanty cytoplasm and pyknotic nuclei. Electron microscopy showed two distinct cell types; an electron-lucent epithelial-appearing cell, and a denser cell with processes containing bundles of filaments and other features suggesting myoepithelial differentiation. Neurosecretory granules were absent. These findings support a salivary duct origin, and are evidence against a neurendocrine derivation for this tumor."} {"id": "PMID:177179", "title": "Estrogen receptor protein in lesions of the male breast: a preliminary report.", "content": "Eleven specimens of breast lesions obtained from 10 male patients were analyzed for estrogen receptor protein (ERP). Three patients (ages 49, 77, 82 years) had infiltrating duct carcinomas with no axillary metastases. ERP in each of these was positive. Eight specimens with gynecomastia, one of which was obtained from the 77-year-old patient with carcinoma in the same breast, were also analyzed. Of these ERP was positive in a 59-year-old man who had cirrhosis of the liver; two patients with borderline ERP had hepatitis and testicular seminoma, respectively. No relationship between histopathologic features of the lesions and ERP results was found and it is too early to relate these ERP studies to prognosis in these patients. Review of available literature, including our cases, reveals that six of eight male breast carcinomas were ERP-positive.", "contents": "Estrogen receptor protein in lesions of the male breast: a preliminary report. Eleven specimens of breast lesions obtained from 10 male patients were analyzed for estrogen receptor protein (ERP). Three patients (ages 49, 77, 82 years) had infiltrating duct carcinomas with no axillary metastases. ERP in each of these was positive. Eight specimens with gynecomastia, one of which was obtained from the 77-year-old patient with carcinoma in the same breast, were also analyzed. Of these ERP was positive in a 59-year-old man who had cirrhosis of the liver; two patients with borderline ERP had hepatitis and testicular seminoma, respectively. No relationship between histopathologic features of the lesions and ERP results was found and it is too early to relate these ERP studies to prognosis in these patients. Review of available literature, including our cases, reveals that six of eight male breast carcinomas were ERP-positive."} {"id": "PMID:177180", "title": "Mucinous carcinoma of the colon and rectum.", "content": "The clinicopathologic significance of mucus production by adenocarcinoma of the colon and rectum was analyzed in retrospective study with stage matched non-mucus producing control carcinomas. Mucinous carcinoma of the colon and rectum comprised 132 (15%) of 893 cases of colorectal carcinoma. The rectum was the most common site (33% of cases). While 120 mucinous cancers had a poorer five-year survival than non-mucinous tumors (34% vs. 53%, p less than .005), these had a particularly bad prognosis in the rectum (18% 5 year survival vs. 49% for the non-mucinous tumor controls, p less than .00k). The theoretical basis for this location-dependent behavior is considered. From this study, distinctive clinico-pathologic features emerge. There were seven documented cases of ulcerative colitis and 8 additional patients gave a history of \"colitis\". An additional five patients had received prior pelvic irradiation. Of particular note was the fact that 31% of mucinous carcinomas were associated with villous adenomas, implying a histogenetic relationship. Moreover, this finding again emphasizes the neoplastic potential of the villous adenoma, especially in the rectum where the development of mucinous carcinoma is particularly ominous.", "contents": "Mucinous carcinoma of the colon and rectum. The clinicopathologic significance of mucus production by adenocarcinoma of the colon and rectum was analyzed in retrospective study with stage matched non-mucus producing control carcinomas. Mucinous carcinoma of the colon and rectum comprised 132 (15%) of 893 cases of colorectal carcinoma. The rectum was the most common site (33% of cases). While 120 mucinous cancers had a poorer five-year survival than non-mucinous tumors (34% vs. 53%, p less than .005), these had a particularly bad prognosis in the rectum (18% 5 year survival vs. 49% for the non-mucinous tumor controls, p less than .00k). The theoretical basis for this location-dependent behavior is considered. From this study, distinctive clinico-pathologic features emerge. There were seven documented cases of ulcerative colitis and 8 additional patients gave a history of \"colitis\". An additional five patients had received prior pelvic irradiation. Of particular note was the fact that 31% of mucinous carcinomas were associated with villous adenomas, implying a histogenetic relationship. Moreover, this finding again emphasizes the neoplastic potential of the villous adenoma, especially in the rectum where the development of mucinous carcinoma is particularly ominous."} {"id": "PMID:177181", "title": "Strumal carcinoid of the ovary.", "content": "A 45-year-old woman presented with an apparently nonfunctioning strumal carcinoid of the ovary. On ultrastructural examination the cells in the solid parts of the tumor as well as in the \"follicular\" areas contained dense-core secretory granules, indicating that this neoplasm is a pure carcinoid tumor. The thyroid-like appearance in areas is due to the accumulation of secretory material within unusually dilated acinar spaces. This study raises the question whether any strumal carcinoid contains thyroid tissue since the cells forming the follicle-like spaces in this tumor contain dense-core granules.", "contents": "Strumal carcinoid of the ovary. A 45-year-old woman presented with an apparently nonfunctioning strumal carcinoid of the ovary. On ultrastructural examination the cells in the solid parts of the tumor as well as in the \"follicular\" areas contained dense-core secretory granules, indicating that this neoplasm is a pure carcinoid tumor. The thyroid-like appearance in areas is due to the accumulation of secretory material within unusually dilated acinar spaces. This study raises the question whether any strumal carcinoid contains thyroid tissue since the cells forming the follicle-like spaces in this tumor contain dense-core granules."} {"id": "PMID:177182", "title": "Localized submassive liver cell necrosis as a terminal event of liver carcinoma.", "content": "Six cases of hepatocellular carcinoma (HCC) and one case of metastatic liver carcinoma in which SGOT, SGPT, and SLDH were suddenly and markedly elevated immediately before death are described. All had a large blood loss and systemic hypotension in the preterminal period; autopsy disclosed irregularly shaped, patchy necrotic areas or infarcts, often clearly demarcated by hemorrhagic rims, in the noncancerous liver parenchyma. Tumor growths in the intrahepatic portal branches were extensive in all six cases with HCC; in the metastatic case, invasion and narrowing of the portal branches were extensive. The incidence of this terminal catastrophe was 3.3% (6 of 184 cases) for HCC and 1.15% (1 of 87) for metastatic carcinoma. The terminal liver necrosis was probably a result of sudden reduction in portal perfusion which had been inadequate because of tumor thrombosis, combined with hypotension of hepatic arteries.", "contents": "Localized submassive liver cell necrosis as a terminal event of liver carcinoma. Six cases of hepatocellular carcinoma (HCC) and one case of metastatic liver carcinoma in which SGOT, SGPT, and SLDH were suddenly and markedly elevated immediately before death are described. All had a large blood loss and systemic hypotension in the preterminal period; autopsy disclosed irregularly shaped, patchy necrotic areas or infarcts, often clearly demarcated by hemorrhagic rims, in the noncancerous liver parenchyma. Tumor growths in the intrahepatic portal branches were extensive in all six cases with HCC; in the metastatic case, invasion and narrowing of the portal branches were extensive. The incidence of this terminal catastrophe was 3.3% (6 of 184 cases) for HCC and 1.15% (1 of 87) for metastatic carcinoma. The terminal liver necrosis was probably a result of sudden reduction in portal perfusion which had been inadequate because of tumor thrombosis, combined with hypotension of hepatic arteries."} {"id": "PMID:177183", "title": "Mediastinoscopy: a diagnostic aid in metastatic carcinoma of the breast.", "content": "Six patients with metastatic carcinoma of the breast underwent mediastinoscopy to obtain tissue for estrogen receptor analysis and pathologic confirmation of metastatic tumor. The indication for mediastioxcopy was an abnormal mediastinal accumulation of gallium in five patients, only two of whom had an abnormality noted on tomography. All six patients had tumor recovered by mediastinoscopy as demonstrated by pathologic examination and/or estrogen receptor assay, Therefore, the diagnosis of mediastinal metastases in breast cancer may be suggested by either chest roentgenograms, mediastinal tomography, or gallium scintigraphy. Mediastinoscopy is a safe, effective procedure capable of establishing the diagnosis of metastatic carcinoma of the breast and of procuring sufficient tissue for estrogen receptor analysis in patients without more readily accessible sites of metastases.", "contents": "Mediastinoscopy: a diagnostic aid in metastatic carcinoma of the breast. Six patients with metastatic carcinoma of the breast underwent mediastinoscopy to obtain tissue for estrogen receptor analysis and pathologic confirmation of metastatic tumor. The indication for mediastioxcopy was an abnormal mediastinal accumulation of gallium in five patients, only two of whom had an abnormality noted on tomography. All six patients had tumor recovered by mediastinoscopy as demonstrated by pathologic examination and/or estrogen receptor assay, Therefore, the diagnosis of mediastinal metastases in breast cancer may be suggested by either chest roentgenograms, mediastinal tomography, or gallium scintigraphy. Mediastinoscopy is a safe, effective procedure capable of establishing the diagnosis of metastatic carcinoma of the breast and of procuring sufficient tissue for estrogen receptor analysis in patients without more readily accessible sites of metastases."} {"id": "PMID:177184", "title": "Peripheral pulmonary carcinoid tumors.", "content": "The light microscopic and ultrastructural features of five asymptomatic peripheral carcinoids presented as distinct pulmonary solitary nodules are described. By conventional microscopy the tumors displayed a variety of histologic patterns, the most unusual one showing tumor cells embedded in a richly vascular hyalinized stroma and forming papillary structures or cystic spaces lined by low cuboidal cells which ultrastructurally bore a strong resemblance to intermediate or transitional forms between types I and II pneumocytes. A striking feature of these tumors was their rich vasculature associated with a marked perivascular sclerosis composed of basement membrane-like material and collagen fibrils most likely produced by the increased numbers of pericytes surrounding these sclerotic vessels. The clinical implications, biologic behavior, and association of these tumors with other pulmonary neoplasms are also discussed.", "contents": "Peripheral pulmonary carcinoid tumors. The light microscopic and ultrastructural features of five asymptomatic peripheral carcinoids presented as distinct pulmonary solitary nodules are described. By conventional microscopy the tumors displayed a variety of histologic patterns, the most unusual one showing tumor cells embedded in a richly vascular hyalinized stroma and forming papillary structures or cystic spaces lined by low cuboidal cells which ultrastructurally bore a strong resemblance to intermediate or transitional forms between types I and II pneumocytes. A striking feature of these tumors was their rich vasculature associated with a marked perivascular sclerosis composed of basement membrane-like material and collagen fibrils most likely produced by the increased numbers of pericytes surrounding these sclerotic vessels. The clinical implications, biologic behavior, and association of these tumors with other pulmonary neoplasms are also discussed."} {"id": "PMID:177185", "title": "Biology of the human malignant lymphomas. III. Intracranial heterotransplantation in the nude, athymic mouse.", "content": "Intracranial heterotransplantation in the nude, athymic mouse has been found to be an effective method for the experimental growth of human malignant lymphomas. Transplants of 11 primary lymphomas and six derived cell lines yielded a high take rate (90%) and a low mean latent period (36 days). Relatively small inocula produced extensive intracerebral infiltrates which could be identified as human in origin by immunofluorescence. Although confined to the central nervous system and meninges, the tumors were highly invasive and displayed morphologic features strikingly similar to those of the original primary tumors. Heterotransplantation of the lymphomas to extracranial sites was only rarely successful. Nude mice previously grafted with isologous neonatal thymuses failed to develop intracerebral tumors. Secondary cell cultures successfully established from several of the intracranial heterotransplants were found to be infected with NIH type-C xenotropic virus. The distinctive growth patterns and other neuropathologic features of the heterotransplants are described, and the relevance of these observations to the development of intracerebral lymphomas in immunosuppressed organ transplant recipients is noted. This method of studying human malignant lymphomas in vivo may permit better histopathologic characterization of the tumors, and may serve as a basis for further experimental lines of investigation, including viral, immunologic, and therapeutic studies.", "contents": "Biology of the human malignant lymphomas. III. Intracranial heterotransplantation in the nude, athymic mouse. Intracranial heterotransplantation in the nude, athymic mouse has been found to be an effective method for the experimental growth of human malignant lymphomas. Transplants of 11 primary lymphomas and six derived cell lines yielded a high take rate (90%) and a low mean latent period (36 days). Relatively small inocula produced extensive intracerebral infiltrates which could be identified as human in origin by immunofluorescence. Although confined to the central nervous system and meninges, the tumors were highly invasive and displayed morphologic features strikingly similar to those of the original primary tumors. Heterotransplantation of the lymphomas to extracranial sites was only rarely successful. Nude mice previously grafted with isologous neonatal thymuses failed to develop intracerebral tumors. Secondary cell cultures successfully established from several of the intracranial heterotransplants were found to be infected with NIH type-C xenotropic virus. The distinctive growth patterns and other neuropathologic features of the heterotransplants are described, and the relevance of these observations to the development of intracerebral lymphomas in immunosuppressed organ transplant recipients is noted. This method of studying human malignant lymphomas in vivo may permit better histopathologic characterization of the tumors, and may serve as a basis for further experimental lines of investigation, including viral, immunologic, and therapeutic studies."} {"id": "PMID:177186", "title": "Cellular whorls in brain tumors other than meningiomas.", "content": "Cellular whorls with or without secondary calcification are generally regarded as reliable diagnostic criteria in the differential diagnosis of meningiomas. They may however occasionally occur in other primary and metastatic brain tumors. Five cases (metastatic laryngeal carcinoma, metastatic mammary carcinoma, metastatic melanoma, medulloblastoma, and giant cell glioblastoma) are presented to illustrate this phenomenon occurring in non-meningothelial brain tumors.", "contents": "Cellular whorls in brain tumors other than meningiomas. Cellular whorls with or without secondary calcification are generally regarded as reliable diagnostic criteria in the differential diagnosis of meningiomas. They may however occasionally occur in other primary and metastatic brain tumors. Five cases (metastatic laryngeal carcinoma, metastatic mammary carcinoma, metastatic melanoma, medulloblastoma, and giant cell glioblastoma) are presented to illustrate this phenomenon occurring in non-meningothelial brain tumors."} {"id": "PMID:177187", "title": "Hepatocellular carcinoma in the Malaysian Orang Asli.", "content": "Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.", "contents": "Hepatocellular carcinoma in the Malaysian Orang Asli. Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people."} {"id": "PMID:177188", "title": "An ultrastructural and histochemical study of the mucous membrane adjacent to and remote from carcinoma of the colon.", "content": "The material was taken from surgical specimens of large intestine resected for carcinoma. A parallel study by electron microscopy and mucin histochemistry was made on fragments from \"transitional\" (TR) mucosa (adjacent to carcinoma) and \"normal\" (N) mucosa (remote from the tumor). These were compared with similar studies on the mucosa from control individuals. Histochemically, the \"TR\" mucosa shows an increase in sialomucins as compared with the \"N\" and control mucosae, where sulphomucins normally predominate. At the ultrastructural level, the \"TR\" mucosa is characterized by the following changes which may precede the histochemical variations: A) alteration in the relative proportions of the different cell types, along the crypt, with a persistence of immature and intermediate cells at higher levels of the crypt than in the control. Mature absorptive cells are fewer and bear an inverse relationship to intermediate cells. Goblet cells are increased in number and size. B) Appearance of electron-dense bodies 0.15-0.3mum in in diameter and membrane limited. C) An elaborated and enlarged Golgi zone showing increased secretory activity. It is suggested that mucin and ultrastructural changes described in the \"TR\" zone may indicate a failure in the normal process of cell differentiation along the crypt. Previous work7,8 further suggests that the mucin changes may be primary, reflecting a cellular response to unknown stimuli (i.e., carcinogens) rather than a local secondary effect of tumor growth. As for the ultrastructural features in the \"TR\" mucosa, the secondary effect cannot be excluded at the present.", "contents": "An ultrastructural and histochemical study of the mucous membrane adjacent to and remote from carcinoma of the colon. The material was taken from surgical specimens of large intestine resected for carcinoma. A parallel study by electron microscopy and mucin histochemistry was made on fragments from \"transitional\" (TR) mucosa (adjacent to carcinoma) and \"normal\" (N) mucosa (remote from the tumor). These were compared with similar studies on the mucosa from control individuals. Histochemically, the \"TR\" mucosa shows an increase in sialomucins as compared with the \"N\" and control mucosae, where sulphomucins normally predominate. At the ultrastructural level, the \"TR\" mucosa is characterized by the following changes which may precede the histochemical variations: A) alteration in the relative proportions of the different cell types, along the crypt, with a persistence of immature and intermediate cells at higher levels of the crypt than in the control. Mature absorptive cells are fewer and bear an inverse relationship to intermediate cells. Goblet cells are increased in number and size. B) Appearance of electron-dense bodies 0.15-0.3mum in in diameter and membrane limited. C) An elaborated and enlarged Golgi zone showing increased secretory activity. It is suggested that mucin and ultrastructural changes described in the \"TR\" zone may indicate a failure in the normal process of cell differentiation along the crypt. Previous work7,8 further suggests that the mucin changes may be primary, reflecting a cellular response to unknown stimuli (i.e., carcinogens) rather than a local secondary effect of tumor growth. As for the ultrastructural features in the \"TR\" mucosa, the secondary effect cannot be excluded at the present."} {"id": "PMID:177189", "title": "Wilms' tumor: natural history and prognostic factors: a retrospective study of 248 cases treated at the Institut Gustave-Roussy 1952-1967.", "content": "A statistical analysis of 248 histologically proven cases of Wilms' tumor treated at the Institut Gustave-Roussy, Villejuif, France, from 1952 to 1967, is presented. Two years recurrence-free survival and five years survival have been selected as prognostic criteria. Patients under two years of age have significantly fewer metastases and a better five-year survival rate than those over two. Stage is stronly correlated with recurrences and survival. Influence of tumor size, number of tumor nodules, tumor rupture, adhesions, regional lymph node involvement, and renal vein infiltration is shown. Detailed analysis of histopathologic features indicates that a favorable clinical course is significantly related to the number of different varieties of epithelial differentiation (tubular, glomerular, microcystic) found in any tumor, whatever the abundance of each of them. Presence of striated muscular cells, however abundant, does not influence survival or metastatic rates. Cases where irradiation given prior to surgery resulted in complete destruction of tumor cells, form a distinctive group of very unfavorable prognosis. Relapse of tumor occurs in 54% of cases, 10% presenting with metastases. Involved sites are listed. No correlation is found between date of metastases and other parameters. The three major prognostic factors of age, stage, histologic pattern, bear prognostic value separately. Stage and age are linked, as well as histology and age. Stage and histology are not linked. Age in itself therefore seems less important. It is concluded that these well-defining treatment for each individual case.", "contents": "Wilms' tumor: natural history and prognostic factors: a retrospective study of 248 cases treated at the Institut Gustave-Roussy 1952-1967. A statistical analysis of 248 histologically proven cases of Wilms' tumor treated at the Institut Gustave-Roussy, Villejuif, France, from 1952 to 1967, is presented. Two years recurrence-free survival and five years survival have been selected as prognostic criteria. Patients under two years of age have significantly fewer metastases and a better five-year survival rate than those over two. Stage is stronly correlated with recurrences and survival. Influence of tumor size, number of tumor nodules, tumor rupture, adhesions, regional lymph node involvement, and renal vein infiltration is shown. Detailed analysis of histopathologic features indicates that a favorable clinical course is significantly related to the number of different varieties of epithelial differentiation (tubular, glomerular, microcystic) found in any tumor, whatever the abundance of each of them. Presence of striated muscular cells, however abundant, does not influence survival or metastatic rates. Cases where irradiation given prior to surgery resulted in complete destruction of tumor cells, form a distinctive group of very unfavorable prognosis. Relapse of tumor occurs in 54% of cases, 10% presenting with metastases. Involved sites are listed. No correlation is found between date of metastases and other parameters. The three major prognostic factors of age, stage, histologic pattern, bear prognostic value separately. Stage and age are linked, as well as histology and age. Stage and histology are not linked. Age in itself therefore seems less important. It is concluded that these well-defining treatment for each individual case."} {"id": "PMID:177192", "title": "The transformation by simian virus 40 of cells from patients with mucopolysaccharidosis and from normal controls.", "content": "Fibroblasts derived from individuals with mucopolysaccharidosis, an inborn error of metabolism, have been found to be more easily transformed by simian virus 40 than are cells derived from normal individuals. The increased susceptibility does not seem to depend upon changes in glycoprotein at the cell surface. Repeated observations were necessary to demonstrate these differences, and we do not believe that this test is suitable for routine screening for cancer susceptibility.", "contents": "The transformation by simian virus 40 of cells from patients with mucopolysaccharidosis and from normal controls. Fibroblasts derived from individuals with mucopolysaccharidosis, an inborn error of metabolism, have been found to be more easily transformed by simian virus 40 than are cells derived from normal individuals. The increased susceptibility does not seem to depend upon changes in glycoprotein at the cell surface. Repeated observations were necessary to demonstrate these differences, and we do not believe that this test is suitable for routine screening for cancer susceptibility."} {"id": "PMID:177191", "title": "Characterization of microsomal methyl sterol demethylase in two Morris hepatomas.", "content": "Previously, we reported that the rate of metabolism of methyl sterol intermediates of cholesterol biosynthesis by broken-cell preparations of Morriss hepatoma 7777 is very slow, whereas the intact tumors are known to synthesize cholesterol quite efficiently. Active preparations have now been obtained by substitution of pyrophosphate for phosphate buffer. Although substitution of pyrophosphate buffer markedly enhances microsomal methyl sterol demethylation rates 3- to 4-fold in hepatoma 7777, other microsomal enzymes and electron carriers in either liver or a more slowly growing hepatoma appear to be unaffected by pyrophosphate. Several properties of the active microsomal methyl sterol demethylase have now been compared for control rat liver, host liver, tumor 7777, and tumor 5123C. Conditions necessary for the assay of initial velocities of enzymic reactions in the tumor microsomes have been established with respect to the amount of protein, time-course, concentrations of cofactors and substrate, pH, and other variables. The K'm and the responses to the variables studied above are very similar for methyl sterol demethylase of microsomes isolated from control liver, host liver, tumor 5123C, and tumor 7777. The multienzymic demethylase in the various preparations has been found to be inhibited similarly by in vitro additions of cyanide, cytochrome c, and bile salts. Thus, the enzymes of the microsomal-bound 4-methyl sterol demethylase of cholesterol biosynthesis appear to be very similar in liver and these 2 Morris hepatomas. When xenobiotic inducers of microsomal oxidases, such as phenobarbital and methylcholanthrene, are administered to normal and tumor-bearing rats, elevated rates of methyl sterol demethylation are observed with isolated liver microsomes obtained from both normal and tumor-bearing rats. Similar increases are not observed in the tumors. Furthermore, daily administration of an intestinal bile acid sequestrant elevates hepatic methyl sterol demethylase, but statistically significant changes were not observed in tumors 7777 and 5123C. Since the enzymes of methyl sterol demethylase appear to be grossly similar in liver and these hepatomas, regulation of the activity of the multienzymic system contained in the tumors may be altered. On the other hand, these agents in vivo simply may not affect liver and the hepatomas similarly, due to a lack of uptake of the foreign substances by the tumor that has been transplanted to the thighs.", "contents": "Characterization of microsomal methyl sterol demethylase in two Morris hepatomas. Previously, we reported that the rate of metabolism of methyl sterol intermediates of cholesterol biosynthesis by broken-cell preparations of Morriss hepatoma 7777 is very slow, whereas the intact tumors are known to synthesize cholesterol quite efficiently. Active preparations have now been obtained by substitution of pyrophosphate for phosphate buffer. Although substitution of pyrophosphate buffer markedly enhances microsomal methyl sterol demethylation rates 3- to 4-fold in hepatoma 7777, other microsomal enzymes and electron carriers in either liver or a more slowly growing hepatoma appear to be unaffected by pyrophosphate. Several properties of the active microsomal methyl sterol demethylase have now been compared for control rat liver, host liver, tumor 7777, and tumor 5123C. Conditions necessary for the assay of initial velocities of enzymic reactions in the tumor microsomes have been established with respect to the amount of protein, time-course, concentrations of cofactors and substrate, pH, and other variables. The K'm and the responses to the variables studied above are very similar for methyl sterol demethylase of microsomes isolated from control liver, host liver, tumor 5123C, and tumor 7777. The multienzymic demethylase in the various preparations has been found to be inhibited similarly by in vitro additions of cyanide, cytochrome c, and bile salts. Thus, the enzymes of the microsomal-bound 4-methyl sterol demethylase of cholesterol biosynthesis appear to be very similar in liver and these 2 Morris hepatomas. When xenobiotic inducers of microsomal oxidases, such as phenobarbital and methylcholanthrene, are administered to normal and tumor-bearing rats, elevated rates of methyl sterol demethylation are observed with isolated liver microsomes obtained from both normal and tumor-bearing rats. Similar increases are not observed in the tumors. Furthermore, daily administration of an intestinal bile acid sequestrant elevates hepatic methyl sterol demethylase, but statistically significant changes were not observed in tumors 7777 and 5123C. Since the enzymes of methyl sterol demethylase appear to be grossly similar in liver and these hepatomas, regulation of the activity of the multienzymic system contained in the tumors may be altered. On the other hand, these agents in vivo simply may not affect liver and the hepatomas similarly, due to a lack of uptake of the foreign substances by the tumor that has been transplanted to the thighs."} {"id": "PMID:177193", "title": "Carcinogenic activity of quinoline on rat liver.", "content": "The effects of prolonged p.o. administration of quinoline or 2-chloroquinoline on rat liver were examined histologically. Hepatocellular carcinomas and hemangioendotheliomas were observed in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% quinoline for about 16 to 40 weeks. However, no neoplastic changes were seen in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% 2-chloroquinoline for 40 weeks. In groups that received low concentrations of quinoline, the incidences of hepatocellular carcinomas were higher and the incidences of hemangioendotheliomas were lower than in the group that received a high concentretion of quinoline. The liver tumors induced by quinoline were classified histologically as hemangioendotheliomas or hemangiosarcomas and trabecular hepatocellular carcinomas. Typical nodular hyperplasias were occasionally seen in the livers of rats treated with quinoline. 2-Chloroquinoline did not induce any nodular hyperplasia or other neoplastic changes, but it caused diffuse fatty changes of parenchymal cells. Oval cell infiltration and bile duct proliferation were slight or moderate. Cirrhotic changes were rare in the livers of rats treated with either quinoline or 2-chloroquinoline. The serum levels of glutamic oxaloacetic transaminase and alkaline phosphatase were slightly changed in groups treated with quinoline, but no other remarkable changes were detected.", "contents": "Carcinogenic activity of quinoline on rat liver. The effects of prolonged p.o. administration of quinoline or 2-chloroquinoline on rat liver were examined histologically. Hepatocellular carcinomas and hemangioendotheliomas were observed in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% quinoline for about 16 to 40 weeks. However, no neoplastic changes were seen in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% 2-chloroquinoline for 40 weeks. In groups that received low concentrations of quinoline, the incidences of hepatocellular carcinomas were higher and the incidences of hemangioendotheliomas were lower than in the group that received a high concentretion of quinoline. The liver tumors induced by quinoline were classified histologically as hemangioendotheliomas or hemangiosarcomas and trabecular hepatocellular carcinomas. Typical nodular hyperplasias were occasionally seen in the livers of rats treated with quinoline. 2-Chloroquinoline did not induce any nodular hyperplasia or other neoplastic changes, but it caused diffuse fatty changes of parenchymal cells. Oval cell infiltration and bile duct proliferation were slight or moderate. Cirrhotic changes were rare in the livers of rats treated with either quinoline or 2-chloroquinoline. The serum levels of glutamic oxaloacetic transaminase and alkaline phosphatase were slightly changed in groups treated with quinoline, but no other remarkable changes were detected."} {"id": "PMID:177194", "title": "Renal neoplastic response to leukosis virus strains BAI A (avian myeloblastosis virus) and MC29.", "content": "Previous reports described the induction of avian renal neoplasms by leukosis virus strains BAI A [avian myeloblastosis virus (AMV)] and MC29, and illustrated morphological characteristics of the tumors. Continued studies in this work confirm evidence of the origin of the tumors from embryonal cells residual in the posthatched chick. The work further emphasizes differences in histopathology of the neoplasms caused by the two viruses and reveals differences in the histopathogenesis of the respective growths. Embryonal rests may consist of two types of cells, those of epithelial characteristics and a second element of differentiation between nephroblastema (mesenchyme) and epithelium and designated here as nephromesoblastoma. Infection by AMV induces tumors of epithelial characteristics and, in addition, derivatives of nephromesoblastoma consisting of cartilage, bone, areas of keratinization, and sarcoma. Keratinized structures in the nephroblastoma originate from nephromesoblastoma. In contrast, MC29 virus induces only epithelial growths representing principally aberrant and malformed glomerular and tubular structures with occasional cartilage derived from epithelial cells. MC29 tumors are completely lacking in nephromesoblastoma tissue and contain no bone, sarcoma, or keratinized formations. In MC29 tumors, occasional cartilage was derived from epithelium. Tumors caused by AMV exhibit the complex structure of nephroblastoma with all of the features of the growth in humans (Wilms' tumor). The neoplasms induced by both AMV and MC29 exhibit marked aberration, distortion, and malformation in the differentiation of the cells growing out from the embryonal rests representing rare manifestations of cell genetic influence inherent in the primordial growth of nephroblastema. The results thus illustrate fundamental differences in cellular composition and capacity to respond to etiologically different leukosis viruses.", "contents": "Renal neoplastic response to leukosis virus strains BAI A (avian myeloblastosis virus) and MC29. Previous reports described the induction of avian renal neoplasms by leukosis virus strains BAI A [avian myeloblastosis virus (AMV)] and MC29, and illustrated morphological characteristics of the tumors. Continued studies in this work confirm evidence of the origin of the tumors from embryonal cells residual in the posthatched chick. The work further emphasizes differences in histopathology of the neoplasms caused by the two viruses and reveals differences in the histopathogenesis of the respective growths. Embryonal rests may consist of two types of cells, those of epithelial characteristics and a second element of differentiation between nephroblastema (mesenchyme) and epithelium and designated here as nephromesoblastoma. Infection by AMV induces tumors of epithelial characteristics and, in addition, derivatives of nephromesoblastoma consisting of cartilage, bone, areas of keratinization, and sarcoma. Keratinized structures in the nephroblastoma originate from nephromesoblastoma. In contrast, MC29 virus induces only epithelial growths representing principally aberrant and malformed glomerular and tubular structures with occasional cartilage derived from epithelial cells. MC29 tumors are completely lacking in nephromesoblastoma tissue and contain no bone, sarcoma, or keratinized formations. In MC29 tumors, occasional cartilage was derived from epithelium. Tumors caused by AMV exhibit the complex structure of nephroblastoma with all of the features of the growth in humans (Wilms' tumor). The neoplasms induced by both AMV and MC29 exhibit marked aberration, distortion, and malformation in the differentiation of the cells growing out from the embryonal rests representing rare manifestations of cell genetic influence inherent in the primordial growth of nephroblastema. The results thus illustrate fundamental differences in cellular composition and capacity to respond to etiologically different leukosis viruses."} {"id": "PMID:177195", "title": "Estrogen and prolactin receptor concentrations in rat mammary tumors and response to endocrine ablation.", "content": "Estrogen and prolactin receptor concentrations were measured in 24 carcinogen-induced rat mammary tumors and correlated with the tumor response to host ovariectomy or hypophysectomy. It was found that essentially all of the tumors contained some specific estrogen receptor, and all but three contained prolactin receptor. The values for each receptor comprised a continuum from very low to relatively high concentrations, suggesting that previous considerations of hormone dependence on the basis of presence or absence of hormone receptors may be oversimplified. The concentration of each receptor tended to be lower in the hormone-independent than in the hormone-dependent tumors, but there were a number of hormone-independent tumors with higher receptor levels than some of the hormone-dependent tumors had. A better correlation of tumor response to endocrine ablation resulted from a combination of the 2 receptor levels than from either receptor concentration alone. These results suggest that there is a complex relationship between mammary tumor response to endocrine ablatin and levels of estrogen and prolactin receptors and that some tumors may be dependent upon 1 or both of these hormones for growth.", "contents": "Estrogen and prolactin receptor concentrations in rat mammary tumors and response to endocrine ablation. Estrogen and prolactin receptor concentrations were measured in 24 carcinogen-induced rat mammary tumors and correlated with the tumor response to host ovariectomy or hypophysectomy. It was found that essentially all of the tumors contained some specific estrogen receptor, and all but three contained prolactin receptor. The values for each receptor comprised a continuum from very low to relatively high concentrations, suggesting that previous considerations of hormone dependence on the basis of presence or absence of hormone receptors may be oversimplified. The concentration of each receptor tended to be lower in the hormone-independent than in the hormone-dependent tumors, but there were a number of hormone-independent tumors with higher receptor levels than some of the hormone-dependent tumors had. A better correlation of tumor response to endocrine ablation resulted from a combination of the 2 receptor levels than from either receptor concentration alone. These results suggest that there is a complex relationship between mammary tumor response to endocrine ablatin and levels of estrogen and prolactin receptors and that some tumors may be dependent upon 1 or both of these hormones for growth."} {"id": "PMID:177196", "title": "Virion interaction in mouse lymphomas.", "content": "Virion expression in filtrates of lymphomas in AKR/J or C3H/HeJ mice was assayed by two techniques: (a) in vitro infectivity (XC assay), or (b) acceleration of oncogenicity in vivo (O assay). The two assays appeared to detect different virus populations or activities. This was shown when the same filtrates were tested in parallel by the XC and O tests and opposite results were obtained on the two assays, e.g., XC+ 0- or XC- O+. It was postulated that two viruses, termed \"XC+\" and \"O\" to correspond to the assays used to detect them, were involved in oncogenesis. When lymphomas originally virus induced were passaged by cells in 2- to 3-month-old syngeneic AKR or C3H mice, oncogenic activity of filtrates of these transplanted lymphomas decreased as cell passages increased. These filtrates from C3H lymphomas also had decreased XC activity as cell passages increased. Normal lymphoid tissue from 1- to 5-month-old AKR mice was XC+ O-, while from C3H mice it was XC- O-. Thus, the two strains modified activities lacking in their normal tissues. Filtrates highly oncogenic in XC+ newborn AKR mice were oncogenic in C3H newborn mice only when sufficient XC+ virus was in the inoculum received by the XC- C3H mice. Thus the XC+ virus appeared to play a synergistic role with a postulated O virus in oncogenesis.", "contents": "Virion interaction in mouse lymphomas. Virion expression in filtrates of lymphomas in AKR/J or C3H/HeJ mice was assayed by two techniques: (a) in vitro infectivity (XC assay), or (b) acceleration of oncogenicity in vivo (O assay). The two assays appeared to detect different virus populations or activities. This was shown when the same filtrates were tested in parallel by the XC and O tests and opposite results were obtained on the two assays, e.g., XC+ 0- or XC- O+. It was postulated that two viruses, termed \"XC+\" and \"O\" to correspond to the assays used to detect them, were involved in oncogenesis. When lymphomas originally virus induced were passaged by cells in 2- to 3-month-old syngeneic AKR or C3H mice, oncogenic activity of filtrates of these transplanted lymphomas decreased as cell passages increased. These filtrates from C3H lymphomas also had decreased XC activity as cell passages increased. Normal lymphoid tissue from 1- to 5-month-old AKR mice was XC+ O-, while from C3H mice it was XC- O-. Thus, the two strains modified activities lacking in their normal tissues. Filtrates highly oncogenic in XC+ newborn AKR mice were oncogenic in C3H newborn mice only when sufficient XC+ virus was in the inoculum received by the XC- C3H mice. Thus the XC+ virus appeared to play a synergistic role with a postulated O virus in oncogenesis."} {"id": "PMID:177197", "title": "Characteristics of a surface-adherent subline derived from Friend erythroleukemia cells in continuous suspension culture.", "content": "A surface-adherent cell population developed spontaneously from Friend erythroleukemia cells (FLC745) which previously had grown continuously in suspension cultures. The adherent cells have been transferred through more than 60 passages and apparently represent a stable variant, herein designated FLC745-Ad. The cell size, chromosome complement, and tumorigenicity in DBA/2 mice were similar to the parental FLC745 line, although the FLC745-Ad cultures grew at a slightly slower rate and synthesized less hemoglobin in response to dimethyl sulfoxide. Production of C-type particles was abundant in both suspension and adherent cells, but the latter appeared to contain more intracisternal A-type particles. Scanning electron microscopy disclosed that most adherent cells were globoid and nonspreading. They attached to the substrate by a circumferential lamellar skirt of unusual breadth. Adhesion of the FLC745-Ad cells was not influenced by serum concentration, trypsinization, 5-bromodeoxyuridine, or N6, O2'-dibutyryl adenosine 3':5'-monophosphate. Treatment with cytochalasin B increased the cell size and the area of cell attachment.", "contents": "Characteristics of a surface-adherent subline derived from Friend erythroleukemia cells in continuous suspension culture. A surface-adherent cell population developed spontaneously from Friend erythroleukemia cells (FLC745) which previously had grown continuously in suspension cultures. The adherent cells have been transferred through more than 60 passages and apparently represent a stable variant, herein designated FLC745-Ad. The cell size, chromosome complement, and tumorigenicity in DBA/2 mice were similar to the parental FLC745 line, although the FLC745-Ad cultures grew at a slightly slower rate and synthesized less hemoglobin in response to dimethyl sulfoxide. Production of C-type particles was abundant in both suspension and adherent cells, but the latter appeared to contain more intracisternal A-type particles. Scanning electron microscopy disclosed that most adherent cells were globoid and nonspreading. They attached to the substrate by a circumferential lamellar skirt of unusual breadth. Adhesion of the FLC745-Ad cells was not influenced by serum concentration, trypsinization, 5-bromodeoxyuridine, or N6, O2'-dibutyryl adenosine 3':5'-monophosphate. Treatment with cytochalasin B increased the cell size and the area of cell attachment."} {"id": "PMID:177198", "title": "Amino acid and hexose transport of normal and simian virus 40-transformed human cells.", "content": "Studies on amino acid and hexose transport were performed on human WI-38 cells and WI-38 SV40-transformed cells (VA13A and VA13-2RA). Depending upon cell line or conditions, either no difference or a relative decrease in initial uptake by transformed cells was found. Under similar growth conditions, transformed hamster cells (PyBHK-21/C13) had increased uptake, compared with the normal hamster cells (BHK-21/C13). The normal and transformed human cells were also similar in sialic acid content and agglutinated when treated with concanavalin A.", "contents": "Amino acid and hexose transport of normal and simian virus 40-transformed human cells. Studies on amino acid and hexose transport were performed on human WI-38 cells and WI-38 SV40-transformed cells (VA13A and VA13-2RA). Depending upon cell line or conditions, either no difference or a relative decrease in initial uptake by transformed cells was found. Under similar growth conditions, transformed hamster cells (PyBHK-21/C13) had increased uptake, compared with the normal hamster cells (BHK-21/C13). The normal and transformed human cells were also similar in sialic acid content and agglutinated when treated with concanavalin A."} {"id": "PMID:177199", "title": "Expression of virion and tumor-specific antigens on the surface of chick embryo cells infected with strain MC29 avian leukosis virus.", "content": "The immunological properties of the surface of chick embryo cells infected with strain MC29 avian leukosis virus were investigated by immune electron microscopy in conjunction with antiviral and anticellular immune sera. When samples were taken at sequential times after infection, it was found that cells stained strongly for viral antigen very early after infection. Staining reached a minimum 6 to 12 hr after infection and then increased to maximum at 15 hr after infection, remaining at this level at later times. Anticellular immune sera showed the presence of a distinct antigen or antigens which appeared concurrently with morphological alteration of the infected chick cells. This antigen was cross-reactive or identical to an antigen appearing on the surface of chick embryo cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus.", "contents": "Expression of virion and tumor-specific antigens on the surface of chick embryo cells infected with strain MC29 avian leukosis virus. The immunological properties of the surface of chick embryo cells infected with strain MC29 avian leukosis virus were investigated by immune electron microscopy in conjunction with antiviral and anticellular immune sera. When samples were taken at sequential times after infection, it was found that cells stained strongly for viral antigen very early after infection. Staining reached a minimum 6 to 12 hr after infection and then increased to maximum at 15 hr after infection, remaining at this level at later times. Anticellular immune sera showed the presence of a distinct antigen or antigens which appeared concurrently with morphological alteration of the infected chick cells. This antigen was cross-reactive or identical to an antigen appearing on the surface of chick embryo cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus."} {"id": "PMID:177200", "title": "Changes in serum putrescine and spermidine levels following local radiation to hepatoma 3924A of the rat.", "content": "Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the spermidine concentration. The decrease in the spermidine concentration of the tumor paralleled increased levels of spermidine in the serum, whereas the concentrations of polyamines in the liver were unchanged. These changes are similar to previously reported changes in the spermidine concentration in sera and in tumors following the administration of a single dose of 5-fluorouracil to rats with 3924A hepatomas. Since local irradiation was confined to the tumor, we conclude that the increases in putrescine and spermidine detected in the serum are derived from the tumor tissue with no involvement of the host tissues.", "contents": "Changes in serum putrescine and spermidine levels following local radiation to hepatoma 3924A of the rat. Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the spermidine concentration. The decrease in the spermidine concentration of the tumor paralleled increased levels of spermidine in the serum, whereas the concentrations of polyamines in the liver were unchanged. These changes are similar to previously reported changes in the spermidine concentration in sera and in tumors following the administration of a single dose of 5-fluorouracil to rats with 3924A hepatomas. Since local irradiation was confined to the tumor, we conclude that the increases in putrescine and spermidine detected in the serum are derived from the tumor tissue with no involvement of the host tissues."} {"id": "PMID:177201", "title": "Isozyme patterns of glycogen phosphorylase in rat tissues and transplantable hepatomas.", "content": "Isozyme patterns of glycogen phosphorylase in the Morris and Yoshida hepatomas were compared electrophoretically and immunochemically with those in rat tissues during development. A 3rd phosphorylase isozyme, observed previously in hepatomas and fetal tissues by isoelectric focusing and by immunochemical titration, was also separated by polyacrylamide disc gel electrophoresis. It was observed commonly in various rat hepatomas, together with variable activities of the liver type, depending on the degree of differentiation. This isozyme is nearly the sole type in placenta and early embryo, and in liver and skeletal muscle it is replaced during fetal development with the organ-specific liver and muscle type. In adult rat brain the fetal type is retained at low levels, together with the muscle type. In kidney, spleen, testis, uterus, lung, and stomach, the fetal type is present together with the liver type. This isozyme in hepatomas and adult brain is identical with the fetal-type, as determined by Ouchterlony double diffusion and activity inhibition tests. Thus, it is considered to be a prototype whose appearance in hepatomas is one of many known examples of fetal protein expression in cancer. In some poorly differentiated hepatomas, the liver-type isozyme migrated slightly more slowly in polyacrylamide gel but could not be distinguished from the liver isozyme immunochemically.", "contents": "Isozyme patterns of glycogen phosphorylase in rat tissues and transplantable hepatomas. Isozyme patterns of glycogen phosphorylase in the Morris and Yoshida hepatomas were compared electrophoretically and immunochemically with those in rat tissues during development. A 3rd phosphorylase isozyme, observed previously in hepatomas and fetal tissues by isoelectric focusing and by immunochemical titration, was also separated by polyacrylamide disc gel electrophoresis. It was observed commonly in various rat hepatomas, together with variable activities of the liver type, depending on the degree of differentiation. This isozyme is nearly the sole type in placenta and early embryo, and in liver and skeletal muscle it is replaced during fetal development with the organ-specific liver and muscle type. In adult rat brain the fetal type is retained at low levels, together with the muscle type. In kidney, spleen, testis, uterus, lung, and stomach, the fetal type is present together with the liver type. This isozyme in hepatomas and adult brain is identical with the fetal-type, as determined by Ouchterlony double diffusion and activity inhibition tests. Thus, it is considered to be a prototype whose appearance in hepatomas is one of many known examples of fetal protein expression in cancer. In some poorly differentiated hepatomas, the liver-type isozyme migrated slightly more slowly in polyacrylamide gel but could not be distinguished from the liver isozyme immunochemically."} {"id": "PMID:177202", "title": "Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator.", "content": "The effects of long-term administration of nafenopin, a potent hypolipidemic drug with marked hepatomegalic and peroxisome-proliferative properties, were studied in wild-type (Csa strain) and acatalasemic (Csb strain) mice. Nafenopin was administered in the diet at a concentration of 0.1% during the first 12 months and then at 0.05% until the termination of the experiment at 20 months. By 56 weeks, 100% mortality occurred in both male and female wild-type mice, whereas the mortality rate in acatalasemic mice was approximately 50%. Between 18 and 20 months of the experiment, 9 of 9 male and 12 of 12 female acatalasemic mice that survived chronic nafenopin treatment developed hepatocellular carcinomas, some of which metastasized to the lungs. None of the 15 male and 15 female acatalasemic controls developed liver cancers. Numerous peroxisomes were seen in the lung metastases of these hepatocellular carcinomas on electron microscopic examination; in contrast the number of peroxisomes in primary liver tumor cells varied considerably. The hepatocarcinogenicity of nafenopin strongly suggests the need for long-term studies with other hypolipidemic drugs that cause hepatomegaly and peroxisome proliferation to clarify the role, if any, of peroxisome proliferation in liver carcinogenesis.", "contents": "Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator. The effects of long-term administration of nafenopin, a potent hypolipidemic drug with marked hepatomegalic and peroxisome-proliferative properties, were studied in wild-type (Csa strain) and acatalasemic (Csb strain) mice. Nafenopin was administered in the diet at a concentration of 0.1% during the first 12 months and then at 0.05% until the termination of the experiment at 20 months. By 56 weeks, 100% mortality occurred in both male and female wild-type mice, whereas the mortality rate in acatalasemic mice was approximately 50%. Between 18 and 20 months of the experiment, 9 of 9 male and 12 of 12 female acatalasemic mice that survived chronic nafenopin treatment developed hepatocellular carcinomas, some of which metastasized to the lungs. None of the 15 male and 15 female acatalasemic controls developed liver cancers. Numerous peroxisomes were seen in the lung metastases of these hepatocellular carcinomas on electron microscopic examination; in contrast the number of peroxisomes in primary liver tumor cells varied considerably. The hepatocarcinogenicity of nafenopin strongly suggests the need for long-term studies with other hypolipidemic drugs that cause hepatomegaly and peroxisome proliferation to clarify the role, if any, of peroxisome proliferation in liver carcinogenesis."} {"id": "PMID:177203", "title": "Transmission of murine leukemia virus (Scripps) from parent to progeny mice as determined by p30 antigenemia.", "content": "All mice of C57BL/St, C3H/St, BALB/cSt, NZB/Scr, and NZW/Lac strains developed high levels of p30 antigenemia after inoculation at birth with murine leukemia virus (Scripps). Transmission of virus from neonatally infected parents to their progeny for three successive generations, as evidenced by development of p30 antigenemia, varied among the five strains. Through the three generations, 100% transmission occurred in C3H/St and BALB/cSt mice, 50 to 61% transmission occurred in C57BL/St and NZW/Lac mice, and 11% transmission to the first generation, with no subsequent transmission, occurred in the NZB/Scr mice. Transmission appeared to occur readily via the milk in all strains. Intrauterine events also played a role with evidence of some viral transfer prior to birth in the C3H/St strain or, conversely, the development of resistance to infection prior to birth in C57BL/St mice. The occurrence of litters from infected parents containing both normal offspring and offspring with elevated p30 appeared to be the result of variable resistance in the intact offspring, perhaps as a result of intrauterine events, and not related to cellular resistance observable in tissue culture or to dominant genetic factors.", "contents": "Transmission of murine leukemia virus (Scripps) from parent to progeny mice as determined by p30 antigenemia. All mice of C57BL/St, C3H/St, BALB/cSt, NZB/Scr, and NZW/Lac strains developed high levels of p30 antigenemia after inoculation at birth with murine leukemia virus (Scripps). Transmission of virus from neonatally infected parents to their progeny for three successive generations, as evidenced by development of p30 antigenemia, varied among the five strains. Through the three generations, 100% transmission occurred in C3H/St and BALB/cSt mice, 50 to 61% transmission occurred in C57BL/St and NZW/Lac mice, and 11% transmission to the first generation, with no subsequent transmission, occurred in the NZB/Scr mice. Transmission appeared to occur readily via the milk in all strains. Intrauterine events also played a role with evidence of some viral transfer prior to birth in the C3H/St strain or, conversely, the development of resistance to infection prior to birth in C57BL/St mice. The occurrence of litters from infected parents containing both normal offspring and offspring with elevated p30 appeared to be the result of variable resistance in the intact offspring, perhaps as a result of intrauterine events, and not related to cellular resistance observable in tissue culture or to dominant genetic factors."} {"id": "PMID:177204", "title": "In vitro growth characteristics of virally transformed murine myeloid cells.", "content": "Bone marrow from normal BALB/c mice, mice with myeloid leukemia induced by Soule myeloid leukemia virus, and mice with virally induced mammary carcinoma was cultured in semisolid agar. Bone marrow from either leukemic or mammary tumor-bearing mice produces more clones in vitro in the presence of a specific colony-stimulating factor. However, in all cases, the myeloid progenitor cells have similar requirements for the colony-stimulating factor. The optimum condition for growth in all instances is 7% fetal calf serum + 7% horse serum + 7% tryptose phosphate broth. Decrease in the concentration of these three constituents has a less drastic effect on in vitro proliferation of bone marrow cells from leukemic mice. Some cells from Soule virus-induced leukemias even grew in the absence of serum. The combination of suboptimal amounts of serum and colony-stimulating factor is used as a tool for detecting cells with altered growth characteristics in bone marrow of leukemic mice. During the progression of the leukemia, there is an increase in the amount of transformed colony-forming cells per 5 X 10(4) bone marrow cells. The increase is already noticeable 4 weeks after inoculation, when no clinical signs of the leukemia are present, and reaches a maximum of about 20%.", "contents": "In vitro growth characteristics of virally transformed murine myeloid cells. Bone marrow from normal BALB/c mice, mice with myeloid leukemia induced by Soule myeloid leukemia virus, and mice with virally induced mammary carcinoma was cultured in semisolid agar. Bone marrow from either leukemic or mammary tumor-bearing mice produces more clones in vitro in the presence of a specific colony-stimulating factor. However, in all cases, the myeloid progenitor cells have similar requirements for the colony-stimulating factor. The optimum condition for growth in all instances is 7% fetal calf serum + 7% horse serum + 7% tryptose phosphate broth. Decrease in the concentration of these three constituents has a less drastic effect on in vitro proliferation of bone marrow cells from leukemic mice. Some cells from Soule virus-induced leukemias even grew in the absence of serum. The combination of suboptimal amounts of serum and colony-stimulating factor is used as a tool for detecting cells with altered growth characteristics in bone marrow of leukemic mice. During the progression of the leukemia, there is an increase in the amount of transformed colony-forming cells per 5 X 10(4) bone marrow cells. The increase is already noticeable 4 weeks after inoculation, when no clinical signs of the leukemia are present, and reaches a maximum of about 20%."} {"id": "PMID:177205", "title": "Accelerated regeneration of trypsin-treated surface antigens of simian virus 40-transformed BALB/3T3 cells induced by X-irradiation.", "content": "The antigens of SV40-transformed BALB/3T3 cells measured by a radioisotopic footpad assay after removal by trypsin treatment regenerated in vitro in 3 to 6 hr. After X-irradiation with 3000 R, however, the antigens were regenerated to normal levels within 1 h. X-ray doses of between 1000 and 5000 R accelerated the regeneration of cell surface antigens, while X-irradiation with the larger dose of 8000 R did not. X-irradiation of nontrypsinized tumor cells was without effect. Possible mechanisms of this phenomenon are discussed.", "contents": "Accelerated regeneration of trypsin-treated surface antigens of simian virus 40-transformed BALB/3T3 cells induced by X-irradiation. The antigens of SV40-transformed BALB/3T3 cells measured by a radioisotopic footpad assay after removal by trypsin treatment regenerated in vitro in 3 to 6 hr. After X-irradiation with 3000 R, however, the antigens were regenerated to normal levels within 1 h. X-ray doses of between 1000 and 5000 R accelerated the regeneration of cell surface antigens, while X-irradiation with the larger dose of 8000 R did not. X-irradiation of nontrypsinized tumor cells was without effect. Possible mechanisms of this phenomenon are discussed."} {"id": "PMID:177206", "title": "Occurrence of the malate-aspartate shuttle in various tumor types.", "content": "The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.", "contents": "Occurrence of the malate-aspartate shuttle in various tumor types. The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm."} {"id": "PMID:177207", "title": "Alanosine toxicity in Novikoff rat hepatoma cells due to inhibition of the conversion of inosine monophosphate to adenosine monophosphate.", "content": "2-Amino-3-(hydroxynitrosoamino)propionic acid (alanosine), at a concentration as low as 2.7 muM, completely inhibits the incorporation of hypoxanthine into adenosine triphosphate by cultured Novikoff rat hepatoma cells. Alanosine inhibits the first step in the conversion of inosine monophosphate to adenosine monophosphate because inosine monophosphate, but not adenylosuccinate, accumulates in treated cells. However, the alanosine inhibition is not prevented by aspartic acid, even at a concentration of 1 mM. Alanosine treatment results in the inhibition of cell division, DNA synthesis, RNA and protein synthesis (in this order), and a depletion of the cells of adenosine triphosphate. Some of the cells accumulate in late G2 or M, but the remainder become arrested in other stages of the cell cycle. All effects are due to the inhibition of adenosine monophosphate synthesis and the consequent depletion of the adenosine triphosphate pool since they are completely prevented or reversed by addition of adenine, but not hypoxanthine, to the medium. Pyrimidine nucleotide synthesis is not significantly inhibited by alanosine, since the uridine triphosphate pool is not affected and uridine fails to reverse the cytotoxicity of alanosine. Alanosine also inhibits the transport of aspartic acid, but has a much lower affinity for this transport system than aspartic acid.", "contents": "Alanosine toxicity in Novikoff rat hepatoma cells due to inhibition of the conversion of inosine monophosphate to adenosine monophosphate. 2-Amino-3-(hydroxynitrosoamino)propionic acid (alanosine), at a concentration as low as 2.7 muM, completely inhibits the incorporation of hypoxanthine into adenosine triphosphate by cultured Novikoff rat hepatoma cells. Alanosine inhibits the first step in the conversion of inosine monophosphate to adenosine monophosphate because inosine monophosphate, but not adenylosuccinate, accumulates in treated cells. However, the alanosine inhibition is not prevented by aspartic acid, even at a concentration of 1 mM. Alanosine treatment results in the inhibition of cell division, DNA synthesis, RNA and protein synthesis (in this order), and a depletion of the cells of adenosine triphosphate. Some of the cells accumulate in late G2 or M, but the remainder become arrested in other stages of the cell cycle. All effects are due to the inhibition of adenosine monophosphate synthesis and the consequent depletion of the adenosine triphosphate pool since they are completely prevented or reversed by addition of adenine, but not hypoxanthine, to the medium. Pyrimidine nucleotide synthesis is not significantly inhibited by alanosine, since the uridine triphosphate pool is not affected and uridine fails to reverse the cytotoxicity of alanosine. Alanosine also inhibits the transport of aspartic acid, but has a much lower affinity for this transport system than aspartic acid."} {"id": "PMID:177209", "title": "Vincristine (NSC-67574) in the treatment of small-cell anaplastic carcinoma of the lung.", "content": "In a phase II trial the effect of vincristine as a single agent was evaluated in patients with small-cell anaplastic carcinoma of the lung. The dosage of vincristine was 1.5 mg/m2/week given iv for 4 weeks, followed by 1.5 mg/m2 given every other week with dose modifications according to neurologic tolerance. Nineteen of 27 patients included in the study were evaluable. Objective response was observed in eight patients (42%) including three who were not previously treated and five who were previously treated. The median duration of response was 60 days (range, 21-182 days) with the response always occurring within 4 weeks. This study demonstrates that vincristine is an active agent for small-cell anaplastic carcinoma without cross resistance to CCNU, cyclophosphamide, or methotrexate.", "contents": "Vincristine (NSC-67574) in the treatment of small-cell anaplastic carcinoma of the lung. In a phase II trial the effect of vincristine as a single agent was evaluated in patients with small-cell anaplastic carcinoma of the lung. The dosage of vincristine was 1.5 mg/m2/week given iv for 4 weeks, followed by 1.5 mg/m2 given every other week with dose modifications according to neurologic tolerance. Nineteen of 27 patients included in the study were evaluable. Objective response was observed in eight patients (42%) including three who were not previously treated and five who were previously treated. The median duration of response was 60 days (range, 21-182 days) with the response always occurring within 4 weeks. This study demonstrates that vincristine is an active agent for small-cell anaplastic carcinoma without cross resistance to CCNU, cyclophosphamide, or methotrexate."} {"id": "PMID:177210", "title": "BCNU (NSC-409962) and procarbazine (NSC-77213) treatment for malignant brain tumors.", "content": "Sixty-five patients with malignant brain tumors were treated with a combination of BCNU (100 mg/m2 qd X 1) and procarbazine (100 mg/m2 qd X 14); the cycle was repeated in 1 month and then on a 6-week schedule with procarbazine being given for 21 days. Forty-five patients had malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma, malignant glioma, or gemistocytic astrocytoma) and were evaluated as a group. All patients had either shown evidence of tumor regrowth after previous surgery and/or radiotherapy, or had deep unbiopsied tumors presumed to be malignant gliomas. Of these 45 patients, 13 of 45 (30%) were judged to be unequivocal responders and an additional eight of 45 (17%) were designated as probable responders. The median duration of clinical response was 34 weeks for responders and 20 weeks for probable responders. The combination of BCNU and procarbazine, therefore, was somewhat inferior to a previous combination of procarbazine, CCNU, and vincristine.", "contents": "BCNU (NSC-409962) and procarbazine (NSC-77213) treatment for malignant brain tumors. Sixty-five patients with malignant brain tumors were treated with a combination of BCNU (100 mg/m2 qd X 1) and procarbazine (100 mg/m2 qd X 14); the cycle was repeated in 1 month and then on a 6-week schedule with procarbazine being given for 21 days. Forty-five patients had malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma, malignant glioma, or gemistocytic astrocytoma) and were evaluated as a group. All patients had either shown evidence of tumor regrowth after previous surgery and/or radiotherapy, or had deep unbiopsied tumors presumed to be malignant gliomas. Of these 45 patients, 13 of 45 (30%) were judged to be unequivocal responders and an additional eight of 45 (17%) were designated as probable responders. The median duration of clinical response was 34 weeks for responders and 20 weeks for probable responders. The combination of BCNU and procarbazine, therefore, was somewhat inferior to a previous combination of procarbazine, CCNU, and vincristine."} {"id": "PMID:177212", "title": "The influence of temperature on the thyroid gland of Chthonerpeton indistinctum (Gymnophiona, Amphibia).", "content": "The thyroid gland of the tropical amphibian Chthonerpeton is markedly stimulated when the animal is exposed for two days to relatively high temperatures (36 degrees C). Control animals were kept at 20 degrees C. The stimulated gland exhibits collapsed follicles and a very tall follicular epithelium. At the ultrastructural level the activated epithelial cells were characterized by an increased number of apical microvilli, increased amounts of rough endoplasmic reticulum, an extended Golgi apparatus and a high number of various granular and vesicular inclusions. These differences in histology and fine structure were not paralleled by quantitative results, which were approximately the same in both groups of animals. The values of these determinations were relatively high.", "contents": "The influence of temperature on the thyroid gland of Chthonerpeton indistinctum (Gymnophiona, Amphibia). The thyroid gland of the tropical amphibian Chthonerpeton is markedly stimulated when the animal is exposed for two days to relatively high temperatures (36 degrees C). Control animals were kept at 20 degrees C. The stimulated gland exhibits collapsed follicles and a very tall follicular epithelium. At the ultrastructural level the activated epithelial cells were characterized by an increased number of apical microvilli, increased amounts of rough endoplasmic reticulum, an extended Golgi apparatus and a high number of various granular and vesicular inclusions. These differences in histology and fine structure were not paralleled by quantitative results, which were approximately the same in both groups of animals. The values of these determinations were relatively high."} {"id": "PMID:177213", "title": "Temperature dependent changes in the thyroid gland of Mertensiella caucasica (Urodela, Amphibia).", "content": "The influence of temperature on the thyroid gland of the Caucasian salamander, Mertensiella caucasica has been studied (1) with the light- and electron microscopes, (2) with enzyme histochemical and quantitative methods. Animals which had been kept for years at 16 degrees C were exposed for 48 hrs to 4 degrees C or 27 degrees C. At 4 degrees C the follicular epithelium consisted of cuboidal cells with well-developed rough ER, occasional distended cisternae of the rough endoplasmic reticulum (ER) filling most of the cytoplasm, a relatively small Golgi apparatus and numerous round or oval shaped lysosomes. In animals kept at 27 degrees C the follicular wall was composed of markedly taller epithelial cells, the apices of which bulged into the follicular lumen. Compared to the animals at 4 degrees C, there appeared to be a decrease in the rough ER. The Golgi apparatus did not exhibit clear differences. The lysosomes increased in number and showed various shapes among which elongated ones with pointed ends were particularly striking. In the apical cytoplasm colloid droplets appeared indicating hormone release. The apical microvilli increased in number. The measurements of total T4 have shown that the hormone level in animals kept at 27 degrees C was about twice as high as in animals kept at 4 degrees C.", "contents": "Temperature dependent changes in the thyroid gland of Mertensiella caucasica (Urodela, Amphibia). The influence of temperature on the thyroid gland of the Caucasian salamander, Mertensiella caucasica has been studied (1) with the light- and electron microscopes, (2) with enzyme histochemical and quantitative methods. Animals which had been kept for years at 16 degrees C were exposed for 48 hrs to 4 degrees C or 27 degrees C. At 4 degrees C the follicular epithelium consisted of cuboidal cells with well-developed rough ER, occasional distended cisternae of the rough endoplasmic reticulum (ER) filling most of the cytoplasm, a relatively small Golgi apparatus and numerous round or oval shaped lysosomes. In animals kept at 27 degrees C the follicular wall was composed of markedly taller epithelial cells, the apices of which bulged into the follicular lumen. Compared to the animals at 4 degrees C, there appeared to be a decrease in the rough ER. The Golgi apparatus did not exhibit clear differences. The lysosomes increased in number and showed various shapes among which elongated ones with pointed ends were particularly striking. In the apical cytoplasm colloid droplets appeared indicating hormone release. The apical microvilli increased in number. The measurements of total T4 have shown that the hormone level in animals kept at 27 degrees C was about twice as high as in animals kept at 4 degrees C."} {"id": "PMID:177214", "title": "Comparative ultrastructural study of the effects of serum-free medium and dibutyryl-cyclic AMP on newborn rat astroblasts.", "content": "Modifications of cell shape induced in cultured newborn rat astroblasts by serum deprivation or dibutyryladenosine 3'-5' monophosphate (dBcAMP) are described. Serum suppression modifies the adhesitivity of the cells to the substrate, but this modification is not consistent with a true differentiation. The main ultrastructural feature of dBcAMP-treated astroblasts is the presence of an extensive system of 90 A microfilaments, while control cells are relatively devoid of these structures.", "contents": "Comparative ultrastructural study of the effects of serum-free medium and dibutyryl-cyclic AMP on newborn rat astroblasts. Modifications of cell shape induced in cultured newborn rat astroblasts by serum deprivation or dibutyryladenosine 3'-5' monophosphate (dBcAMP) are described. Serum suppression modifies the adhesitivity of the cells to the substrate, but this modification is not consistent with a true differentiation. The main ultrastructural feature of dBcAMP-treated astroblasts is the presence of an extensive system of 90 A microfilaments, while control cells are relatively devoid of these structures."} {"id": "PMID:177215", "title": "Extracellular cyclic-amp phosphodiesterase regulation in agar plate cultures of Dictyostelium discoideum.", "content": "Extracellular cyclic-AMP phosphodiesterase and the inhibitor of this enzyme is tested in agar plate cultures of two Dictyostelium discoideum wild-type strains and in a mutant which lacks the inhibitor. Under the conditions used, the phosphodiesterase inhibitor is formed in both wild-type strains either before or in an early stage of cell aggregation. During aggregation of one strain the phosphodiesterase activity is extremely low, excluding a necessary function of the enzyme in the aggregation process.", "contents": "Extracellular cyclic-amp phosphodiesterase regulation in agar plate cultures of Dictyostelium discoideum. Extracellular cyclic-AMP phosphodiesterase and the inhibitor of this enzyme is tested in agar plate cultures of two Dictyostelium discoideum wild-type strains and in a mutant which lacks the inhibitor. Under the conditions used, the phosphodiesterase inhibitor is formed in both wild-type strains either before or in an early stage of cell aggregation. During aggregation of one strain the phosphodiesterase activity is extremely low, excluding a necessary function of the enzyme in the aggregation process."} {"id": "PMID:177216", "title": "Expression of differentiative traits in the absence of cell fusion during myogenesis in culture.", "content": "Fusion of myoblasts is inhibited in cultures at low Ca++ concentration (0.44 mM); yet creatine phosphokinase and myokinase activities as well as myosin synthesis and the appearance of post-mitotic myoblasts do not significantly differ from those of control cultures (grown at 1.04 mM Ca++) which undergo cell fusion. When Ca++ concentration is increased to the control value after the second day of culture, fusion occurs very rapidly and it is not inhibited by actinomycin D or cycloheximide. Treatment with 0.06 mM bromodeoxyuridine strongly inhibits creatine phosphokinase activity and myotubes formation. The study of the kinetics of reversal of cell fusion and of creatine phosphokinase activity after removal of the analog, shows that this process is slower than the decrease of the relative content of bromodeoxyuridine incorporated into DNA. The result obtained support the following conclusions: a) the expression of the differentiative characters examined does not require cell fusion; b) the process of myotube formation seems to imply two subsequent stages consisting first of a slow maturative process, which is followed by the actual fusion of cell membranes; the former is Ca++ independent, the latter is Ca++ dependent and does not require RNA or protein synthesis.", "contents": "Expression of differentiative traits in the absence of cell fusion during myogenesis in culture. Fusion of myoblasts is inhibited in cultures at low Ca++ concentration (0.44 mM); yet creatine phosphokinase and myokinase activities as well as myosin synthesis and the appearance of post-mitotic myoblasts do not significantly differ from those of control cultures (grown at 1.04 mM Ca++) which undergo cell fusion. When Ca++ concentration is increased to the control value after the second day of culture, fusion occurs very rapidly and it is not inhibited by actinomycin D or cycloheximide. Treatment with 0.06 mM bromodeoxyuridine strongly inhibits creatine phosphokinase activity and myotubes formation. The study of the kinetics of reversal of cell fusion and of creatine phosphokinase activity after removal of the analog, shows that this process is slower than the decrease of the relative content of bromodeoxyuridine incorporated into DNA. The result obtained support the following conclusions: a) the expression of the differentiative characters examined does not require cell fusion; b) the process of myotube formation seems to imply two subsequent stages consisting first of a slow maturative process, which is followed by the actual fusion of cell membranes; the former is Ca++ independent, the latter is Ca++ dependent and does not require RNA or protein synthesis."} {"id": "PMID:177219", "title": "Spin label studies of micellar and pre-micellar aggregates.", "content": "Micelles of hexadecyl trimethyl ammonium bromide (CTABr) have been investigated with the use of a faty acid spin label and its methyl ester derivative. The esr * spectra provided information about the degree of motion of the probes in the micelles as evaluated from calculation of rotational correlation times. Evidence is presented for the formation of pre-micellar aggregates at concentrations below the cmc. The effect of addition of thiophenoxide on the structure of CTABr micelles was to decrease the rate of motion of the spin probes, probably due to a tighter packing of the hydrophobic core as a consequence of charge neutralization at the micelle surface by the substrate. Decreasing values of the isotropic hyperfine splitting of the spin probe with increasing concentration of thiophenoxide were taken as indicating that the latter causes a decrease of the degree of hydration of the polar head region of the detergent.", "contents": "Spin label studies of micellar and pre-micellar aggregates. Micelles of hexadecyl trimethyl ammonium bromide (CTABr) have been investigated with the use of a faty acid spin label and its methyl ester derivative. The esr * spectra provided information about the degree of motion of the probes in the micelles as evaluated from calculation of rotational correlation times. Evidence is presented for the formation of pre-micellar aggregates at concentrations below the cmc. The effect of addition of thiophenoxide on the structure of CTABr micelles was to decrease the rate of motion of the spin probes, probably due to a tighter packing of the hydrophobic core as a consequence of charge neutralization at the micelle surface by the substrate. Decreasing values of the isotropic hyperfine splitting of the spin probe with increasing concentration of thiophenoxide were taken as indicating that the latter causes a decrease of the degree of hydration of the polar head region of the detergent."} {"id": "PMID:177220", "title": "Synthesis of 2-n-(hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine-hydroxide, a chromogenic substrate for assaying sphingomyelinase activity.", "content": "2-N-(Hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine-hydroxide a compound resembling sphingomyelin is synthesized. It is cleaved by sphingomyelinase to the chromogenic N-acylaminonitrophenyl moiety. Phospholipase C preparations do not hydrolyze this compound. The starting material is 2-amino-4-nitrophenol which when acylated with palmitoyl chloride yields the hexadecananilide. Reaction with beta-bromoethylphosphoryldichloride gives the phosphate which is quaternized with trimethylamine to give the title compound.", "contents": "Synthesis of 2-n-(hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine-hydroxide, a chromogenic substrate for assaying sphingomyelinase activity. 2-N-(Hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine-hydroxide a compound resembling sphingomyelin is synthesized. It is cleaved by sphingomyelinase to the chromogenic N-acylaminonitrophenyl moiety. Phospholipase C preparations do not hydrolyze this compound. The starting material is 2-amino-4-nitrophenol which when acylated with palmitoyl chloride yields the hexadecananilide. Reaction with beta-bromoethylphosphoryldichloride gives the phosphate which is quaternized with trimethylamine to give the title compound."} {"id": "PMID:177222", "title": "[Meiosis: role of a histone kinase in the condensation of ovarian oocyte chromosomes of Xenopus laevis and Ambystoma mexicanum].", "content": "By injecting heterologous histone-kinase preparations into ovarian Axolotl oocytes, it has been possible to speed up the progesterone-induced process of chromosome condensation. Moreover, in some instances, this condensation and even complete maturation have been obtained after injection of protein kinase alone, thus in the absence of hormone stimulation. Two different histone kinase preparations have been used: one was prepared from ascites cell chromatin and the other from in vitro ovulated Xenopus oocytes.", "contents": "[Meiosis: role of a histone kinase in the condensation of ovarian oocyte chromosomes of Xenopus laevis and Ambystoma mexicanum]. By injecting heterologous histone-kinase preparations into ovarian Axolotl oocytes, it has been possible to speed up the progesterone-induced process of chromosome condensation. Moreover, in some instances, this condensation and even complete maturation have been obtained after injection of protein kinase alone, thus in the absence of hormone stimulation. Two different histone kinase preparations have been used: one was prepared from ascites cell chromatin and the other from in vitro ovulated Xenopus oocytes."} {"id": "PMID:177223", "title": "[Autoradiographic study of a bacterial colony. Application to the effects of polymyxin on Pseudomonas aeruginosa colonies].", "content": "The autoradiograph of a colony of Ps. a. which has been transferred, during growth, on a medium added with polymyxin and tritiate leucin makes it possible to locate an upper zone with a high metabolic activity and a basal zone with no metabolic activity. The latter, which consists of lysed cells, acts probably as a selective filter against the drug.", "contents": "[Autoradiographic study of a bacterial colony. Application to the effects of polymyxin on Pseudomonas aeruginosa colonies]. The autoradiograph of a colony of Ps. a. which has been transferred, during growth, on a medium added with polymyxin and tritiate leucin makes it possible to locate an upper zone with a high metabolic activity and a basal zone with no metabolic activity. The latter, which consists of lysed cells, acts probably as a selective filter against the drug."} {"id": "PMID:177224", "title": "[Maternal and fetal corticosteroids in the sow at the end of gestation].", "content": "Foetal and maternal blood samples are taken on the sow at the end of pregnancy. No variations in maternal cortisol are found, but plasma cortisol levels in the foetus, which are relatively constant between days 70 and 100 of pregnancy (10 to 20 ng/ml), increase suddenly at the end of pregnancy reaching a mean of 210 ng/ml at birth. This high increase of foetal corticosteroids at birth, similar to that found in other species (ewe, goat, etc.), probably plays a role in the mechanisms releasing parturition. It also permits us to understand the action of ACTH which induces premature birth when given to the pig foetus in the last days of pregnancy.", "contents": "[Maternal and fetal corticosteroids in the sow at the end of gestation]. Foetal and maternal blood samples are taken on the sow at the end of pregnancy. No variations in maternal cortisol are found, but plasma cortisol levels in the foetus, which are relatively constant between days 70 and 100 of pregnancy (10 to 20 ng/ml), increase suddenly at the end of pregnancy reaching a mean of 210 ng/ml at birth. This high increase of foetal corticosteroids at birth, similar to that found in other species (ewe, goat, etc.), probably plays a role in the mechanisms releasing parturition. It also permits us to understand the action of ACTH which induces premature birth when given to the pig foetus in the last days of pregnancy."} {"id": "PMID:177225", "title": "[The mode of action of bacteriocin N5 purified from Clostridium perfringens].", "content": "The purified bacteriocin N5 produced by Clostridium perfringens BP6K inhibited simultaneously the syntheses of DNA, RNA and protein in sensitive cells, without DNA degradation. Bacteriocin N5 inhibited the accumulation of leucin and caused the exit of the previously accumulated amino acid. The effects of bacteriocin N5 are very similar to those observed for colicins E1, K, A and I.", "contents": "[The mode of action of bacteriocin N5 purified from Clostridium perfringens]. The purified bacteriocin N5 produced by Clostridium perfringens BP6K inhibited simultaneously the syntheses of DNA, RNA and protein in sensitive cells, without DNA degradation. Bacteriocin N5 inhibited the accumulation of leucin and caused the exit of the previously accumulated amino acid. The effects of bacteriocin N5 are very similar to those observed for colicins E1, K, A and I."} {"id": "PMID:177226", "title": "[Changes in the level of ACTH in the fetal hypophysis. A study in the rat toward the end of gestation].", "content": "The isolated adrenal cell method for bioassay of ACTH was employed in order to determine the ACTH content of the hypophysis of the rat foetus, in late pregnancy. The ACTH concentration decreases between 17 days 8 h and 17 days 15 h, then it increases regularly until the term. This evolution is correlated with the change in the fluorescence intensity of the corticotrophs and with the modification of the adrenocortical activity.", "contents": "[Changes in the level of ACTH in the fetal hypophysis. A study in the rat toward the end of gestation]. The isolated adrenal cell method for bioassay of ACTH was employed in order to determine the ACTH content of the hypophysis of the rat foetus, in late pregnancy. The ACTH concentration decreases between 17 days 8 h and 17 days 15 h, then it increases regularly until the term. This evolution is correlated with the change in the fluorescence intensity of the corticotrophs and with the modification of the adrenocortical activity."} {"id": "PMID:177227", "title": "[The effect of an ionophore on the aggregation of Dictyostelium discoideum].", "content": "Treatment during starvation of D. discoideum amoebae with micromolar amounts of A23187 causes an enhanced aggregation. Cells develop the properties of differentiated, aggregation competent amoebae earlier than untreated populations. Ionophore increases the release of calcium, and prevents the excretion of the phosphodiesterase ihibitor normally released in the media. A23187 suppresses the morphogenetic block of some aggregates mutants, suggesting that the ionophore either activates cAMP synthesis and excretion, or increases the cellular sensitivity to extracellular cAMP signals. This might result from the enhanced mobilisation of intracellular calcium", "contents": "[The effect of an ionophore on the aggregation of Dictyostelium discoideum]. Treatment during starvation of D. discoideum amoebae with micromolar amounts of A23187 causes an enhanced aggregation. Cells develop the properties of differentiated, aggregation competent amoebae earlier than untreated populations. Ionophore increases the release of calcium, and prevents the excretion of the phosphodiesterase ihibitor normally released in the media. A23187 suppresses the morphogenetic block of some aggregates mutants, suggesting that the ionophore either activates cAMP synthesis and excretion, or increases the cellular sensitivity to extracellular cAMP signals. This might result from the enhanced mobilisation of intracellular calcium"} {"id": "PMID:177228", "title": "Technetium 99m stannous pyrophosphate myocardial imaging in patients with and without left ventricular aneurysm.", "content": "To further explore the usefulness of technetium 99m pyrophosphate (99mTc-PYP) myocardial imaging and test its validity in the diagnosis of acute myocardial infarction, 99mTc-PYP myocardial scintigrams were performed in 50 patients. Out of 28 patients with acute myocardial infarction, myocardial scintigrams demonstrated localized activity in the 15 patients with transmural, and diffuse activity in the 13 patients with subendocardial myocardial infarction. Twenty-two patients with significant coronary artery disease documented by coronary angiography but without acute myocardial infarction were also studied. Nine of ten patients with clinical evidence of left ventricular aneurysm from previous myocardial infarction and definite left ventricular dyskinesis had positive scintigrams with activity localized to the site of the wall motion abnormality. Two of five patients without definite aneurysm but with left ventricular akinesis also had localized uptake in the involved area of the left ventricle. Seven patients with normal left ventricular wall motion had negative scintigrams. These findings suggest caution in interpreting positive 99mTc-PYP scintigrams as being indicative of acute myocardial infarction when evidence of a left ventricular aneurysm is also present.", "contents": "Technetium 99m stannous pyrophosphate myocardial imaging in patients with and without left ventricular aneurysm. To further explore the usefulness of technetium 99m pyrophosphate (99mTc-PYP) myocardial imaging and test its validity in the diagnosis of acute myocardial infarction, 99mTc-PYP myocardial scintigrams were performed in 50 patients. Out of 28 patients with acute myocardial infarction, myocardial scintigrams demonstrated localized activity in the 15 patients with transmural, and diffuse activity in the 13 patients with subendocardial myocardial infarction. Twenty-two patients with significant coronary artery disease documented by coronary angiography but without acute myocardial infarction were also studied. Nine of ten patients with clinical evidence of left ventricular aneurysm from previous myocardial infarction and definite left ventricular dyskinesis had positive scintigrams with activity localized to the site of the wall motion abnormality. Two of five patients without definite aneurysm but with left ventricular akinesis also had localized uptake in the involved area of the left ventricle. Seven patients with normal left ventricular wall motion had negative scintigrams. These findings suggest caution in interpreting positive 99mTc-PYP scintigrams as being indicative of acute myocardial infarction when evidence of a left ventricular aneurysm is also present."} {"id": "PMID:177230", "title": "Demonstration and semiquantitative determination of complexes between various proteases and human alpha2-macroglobulin.", "content": "Complex formation in vitro between human alpha2-macroglobulin and the human proteases cationic trypsin, chymotrypsin, plasmin and granulocyte elastase and collagenase was clearly visualized by the use of thin-layer electrofocusing in polyacrylamide gel followed by electrophoresis in agarose gel containing antibodies against human alpha2-macroglobulin. The technique permits semi-quantitative determination of the amount of complex and can demonstrate the formation of complexes between alpha2-macroglobulin and protease in vivo in ascitic fluid in peritonitis.", "contents": "Demonstration and semiquantitative determination of complexes between various proteases and human alpha2-macroglobulin. Complex formation in vitro between human alpha2-macroglobulin and the human proteases cationic trypsin, chymotrypsin, plasmin and granulocyte elastase and collagenase was clearly visualized by the use of thin-layer electrofocusing in polyacrylamide gel followed by electrophoresis in agarose gel containing antibodies against human alpha2-macroglobulin. The technique permits semi-quantitative determination of the amount of complex and can demonstrate the formation of complexes between alpha2-macroglobulin and protease in vivo in ascitic fluid in peritonitis."} {"id": "PMID:177231", "title": "Neonatal screening for hyperlipoproteinemia. Methods for direct estimation of cord serum VLDL + LDL.", "content": "The early detection of hyperlipoproteinemia in newborn infants has so far been based upon estimation of cord blood total lipids (cholesterol and triglyceride) and lipoprotein-lipids (VLDL-, LDL- and HDL-cholesterol). To be able to make a direct estimation of cord serum beta-lipoproteins (VLDL + LDL) two quite different methods were modified, one immunological and the other turbidimetric. Good correlations were found to VLDL- + LDL-cholesterol isolated in the ultracentrifuge (r = 0.848 and 0.831, respectively). If neonatal screening for hyperlipoproteinemia is considered, we recommend the very easy and inexpensive turbidimetric method. Furthermore, using cord serum, two conventional precipitation methods with heparin-CaCl2 and heparin-MnCl2 were compared by ultracentrifugation and high correlations were found (r = 0.923 and 0.899, respectively). A clamping study showed that following early clamping of the cord, the concentration of cord serum lipids and lipoproteins did not change markedly within the first five minutes. Storing experiments showed that serum should be separated within the first 12 h to avoid unpredictable changes in the concentration of cord serum lipids and lipoproteins.", "contents": "Neonatal screening for hyperlipoproteinemia. Methods for direct estimation of cord serum VLDL + LDL. The early detection of hyperlipoproteinemia in newborn infants has so far been based upon estimation of cord blood total lipids (cholesterol and triglyceride) and lipoprotein-lipids (VLDL-, LDL- and HDL-cholesterol). To be able to make a direct estimation of cord serum beta-lipoproteins (VLDL + LDL) two quite different methods were modified, one immunological and the other turbidimetric. Good correlations were found to VLDL- + LDL-cholesterol isolated in the ultracentrifuge (r = 0.848 and 0.831, respectively). If neonatal screening for hyperlipoproteinemia is considered, we recommend the very easy and inexpensive turbidimetric method. Furthermore, using cord serum, two conventional precipitation methods with heparin-CaCl2 and heparin-MnCl2 were compared by ultracentrifugation and high correlations were found (r = 0.923 and 0.899, respectively). A clamping study showed that following early clamping of the cord, the concentration of cord serum lipids and lipoproteins did not change markedly within the first five minutes. Storing experiments showed that serum should be separated within the first 12 h to avoid unpredictable changes in the concentration of cord serum lipids and lipoproteins."} {"id": "PMID:177232", "title": "Serum alkaline phosphatase, nucleotide pyrophosphatase, 5'-nucleotide and lipoprotein-X in cholestasis.", "content": "The nature of the stationary band of alkaline phosphatase, which occurs on starch gel electrophoresis of sera from patients with biliary obstruction, has been examined. Stationary alkaline phosphatase was eluted from Sepharose 4-B gel close to the void volume and together with the plasma membrane enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, and with lipoprotein-X. Electron microscopy of concentrates of stationary alkaline phosphatase, prepared by ultracentrifugation and gel filtration, showed large (0.3--1 mum diameter) and small structures (30-70 nm diameter) by negative staining. The activity of the stationary alkaline phosphatase was associated in fixed sections with particles of about 10 nm X 40 nm resembling those of lipoprotein-X. It is suggested that the stationary alkaline phosphatase does not move into starch gel during electrophoresis because it is particulate. In agar electrophoresis the alkaline phosphatase which was stationary on starch gel moved towards the cathode with lipoprotein-X.", "contents": "Serum alkaline phosphatase, nucleotide pyrophosphatase, 5'-nucleotide and lipoprotein-X in cholestasis. The nature of the stationary band of alkaline phosphatase, which occurs on starch gel electrophoresis of sera from patients with biliary obstruction, has been examined. Stationary alkaline phosphatase was eluted from Sepharose 4-B gel close to the void volume and together with the plasma membrane enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, and with lipoprotein-X. Electron microscopy of concentrates of stationary alkaline phosphatase, prepared by ultracentrifugation and gel filtration, showed large (0.3--1 mum diameter) and small structures (30-70 nm diameter) by negative staining. The activity of the stationary alkaline phosphatase was associated in fixed sections with particles of about 10 nm X 40 nm resembling those of lipoprotein-X. It is suggested that the stationary alkaline phosphatase does not move into starch gel during electrophoresis because it is particulate. In agar electrophoresis the alkaline phosphatase which was stationary on starch gel moved towards the cathode with lipoprotein-X."} {"id": "PMID:177234", "title": "A simplified competitive protein-binding assay for 25-hydroxycalciferol.", "content": "A single and reliable, competitive, protein-binding assay for plasma 25-hydroxycalciferol (25-OH-D), based on a previously described method which omits the chromatographic step, has been tested without the use of beta-lipoproteins. The accuracy is similar in the absence of beta-lipoproteins and in their presence, the recoveries being respectively 110-136% and 74-85%. The intraassay coefficient of variation is 7.23% in the absence versus 12.56% in the presence of beta-lipoproteins. The sensitivity of the described assay is 0.01 ng per assay tube and 1 mug/1 plasma. The mean plasma 25-OH-D level in eighteen normal Swiss volunteers aged 20 to 40 years is 39.5 +/- S.D. 9.3 mug/l. This level is similar to those found in Western Europe and U.S.A. subjects. Ten alcoholic patients without cirrhosis have significantly lower 25-OH-D plasma levels (13.0 +/- S.D. 8.9 mug/l) than appropriate age controls. This precise and accurate method is convenient for clinical studies since both chromatographic and beta-lipoproteins steps are avoided.", "contents": "A simplified competitive protein-binding assay for 25-hydroxycalciferol. A single and reliable, competitive, protein-binding assay for plasma 25-hydroxycalciferol (25-OH-D), based on a previously described method which omits the chromatographic step, has been tested without the use of beta-lipoproteins. The accuracy is similar in the absence of beta-lipoproteins and in their presence, the recoveries being respectively 110-136% and 74-85%. The intraassay coefficient of variation is 7.23% in the absence versus 12.56% in the presence of beta-lipoproteins. The sensitivity of the described assay is 0.01 ng per assay tube and 1 mug/1 plasma. The mean plasma 25-OH-D level in eighteen normal Swiss volunteers aged 20 to 40 years is 39.5 +/- S.D. 9.3 mug/l. This level is similar to those found in Western Europe and U.S.A. subjects. Ten alcoholic patients without cirrhosis have significantly lower 25-OH-D plasma levels (13.0 +/- S.D. 8.9 mug/l) than appropriate age controls. This precise and accurate method is convenient for clinical studies since both chromatographic and beta-lipoproteins steps are avoided."} {"id": "PMID:177235", "title": "Three siblings with Robert's syndrome.", "content": "A Yugoslavian family with one female and two male infants with Robert's syndrome is described. The main features were: (1) tetraphocomelia with missing or malformed bones of arms and legs; (2) bilateral cleft lip and palate; (3) ectrodactyly; (4) syndactyly of the digits; (5) hypertelorism with exophthalmos at birth; (6) congenital heart defect; (7) low birth weight and failure to thrive. These observations raise the reported cases of Robert's syndrome--including questionable ones--to a total of 26. The most likely basic etiology is a major single recessive gene mutation.", "contents": "Three siblings with Robert's syndrome. A Yugoslavian family with one female and two male infants with Robert's syndrome is described. The main features were: (1) tetraphocomelia with missing or malformed bones of arms and legs; (2) bilateral cleft lip and palate; (3) ectrodactyly; (4) syndactyly of the digits; (5) hypertelorism with exophthalmos at birth; (6) congenital heart defect; (7) low birth weight and failure to thrive. These observations raise the reported cases of Robert's syndrome--including questionable ones--to a total of 26. The most likely basic etiology is a major single recessive gene mutation."} {"id": "PMID:177236", "title": "Immunodeficiency in the chicken. IV. An immunological study of infectious bursal disease.", "content": "Chickens inoculated orally with infectious bursal disease virus (IBDV) 1 day after hatching subsequently showed a 50% incidence of immunodeficiency but little mortality. Antibody responses against IBDV and to immunization with sheep red blood cells (SRBC) or human serum albumin (HSA) were suppressed. Serum IgG concentration was decreased while IgM occurred exclusively in its 7S monomeric form (mIgM). An allotypic marker of chicken IgM (Mla) was lacking in mIgM derived from IBDV-infected birds. The loss of Mla occurred gradually in several birds between 3 and 12 weeks after perinatal infection. Inoculation of IBDV into chickens 3 weeks after hatching resulted in 50% mortality level but little immunodeficiency. Paradoxically, the serum IgG concentration was elevated, in comparison with normal birds. Histology of the bursa showed permanent hypo- or aplasia of follicles irrespective of the age of infection. The results suggest that bursal but not peripheral B cells are targets for IBDV, and immunodeficiency results from impaired peripheral seeding of B cells in infected juvenile chickens.", "contents": "Immunodeficiency in the chicken. IV. An immunological study of infectious bursal disease. Chickens inoculated orally with infectious bursal disease virus (IBDV) 1 day after hatching subsequently showed a 50% incidence of immunodeficiency but little mortality. Antibody responses against IBDV and to immunization with sheep red blood cells (SRBC) or human serum albumin (HSA) were suppressed. Serum IgG concentration was decreased while IgM occurred exclusively in its 7S monomeric form (mIgM). An allotypic marker of chicken IgM (Mla) was lacking in mIgM derived from IBDV-infected birds. The loss of Mla occurred gradually in several birds between 3 and 12 weeks after perinatal infection. Inoculation of IBDV into chickens 3 weeks after hatching resulted in 50% mortality level but little immunodeficiency. Paradoxically, the serum IgG concentration was elevated, in comparison with normal birds. Histology of the bursa showed permanent hypo- or aplasia of follicles irrespective of the age of infection. The results suggest that bursal but not peripheral B cells are targets for IBDV, and immunodeficiency results from impaired peripheral seeding of B cells in infected juvenile chickens."} {"id": "PMID:177238", "title": "Neoplasia in patients with chronic renal failure on long-term dialysis.", "content": "Out of 67 patients accepted for maintenance dialysis (56 for hemodialysis and 11 for peritoneal dialysis) 47 had not received any form of immunosuppression either in connection with renal transplantation or as part of the therapy for their intrinsic renal disease. Six out of the 47 patients (12.8%) were found to have malignancies which were not directly causing their renal failure. Two patients had carcinomas of the kidney, 2 patients had skin cancers, 1 patient had a carcinoma of the stomach and 1 patient had a carcinoid tumour of the small intestine. This raises the question whether prolongation of uremia by long term dialysis may contribute to the development of malignancy by increasing longevity in the chronically immunosuppressed uremic state.", "contents": "Neoplasia in patients with chronic renal failure on long-term dialysis. Out of 67 patients accepted for maintenance dialysis (56 for hemodialysis and 11 for peritoneal dialysis) 47 had not received any form of immunosuppression either in connection with renal transplantation or as part of the therapy for their intrinsic renal disease. Six out of the 47 patients (12.8%) were found to have malignancies which were not directly causing their renal failure. Two patients had carcinomas of the kidney, 2 patients had skin cancers, 1 patient had a carcinoma of the stomach and 1 patient had a carcinoid tumour of the small intestine. This raises the question whether prolongation of uremia by long term dialysis may contribute to the development of malignancy by increasing longevity in the chronically immunosuppressed uremic state."} {"id": "PMID:177242", "title": "One-year trials with halofenate, clofibrate, and placebo.", "content": "The hypolipidemic as well as other laboratory and clinical effects of halofenate, clofibrate, and placebo were compared in 29 patients with type IV hyperlipoproteinemia in a double-blind, controlled, therapeutic trial of 1 yr duration. Plasma drug levels were obtained to monitor compliance. Clofibrate and halofenate lowered serum triglycerides to a similar extent. The hypotriglyceridemic effect of halofenate was significant only when data from noncompliant patients were discarded. Only clofibrate lowered baseline levels of plasma cholesterol. Very low density lipoproteins were decreased and low density lipoproteins were increased by clofibrate but not by halofenate. Halofenate had a marked hypouricemic effect that was greater than that of clofibrate. The hypouricemic effect of halofenate and clofibrate was paralleled by a concomitant decrease in serum bilirubin. Abnormal increases in serum creatine phosphokinase were observed with both drugs primarily in patients who had abnormal initial levels.", "contents": "One-year trials with halofenate, clofibrate, and placebo. The hypolipidemic as well as other laboratory and clinical effects of halofenate, clofibrate, and placebo were compared in 29 patients with type IV hyperlipoproteinemia in a double-blind, controlled, therapeutic trial of 1 yr duration. Plasma drug levels were obtained to monitor compliance. Clofibrate and halofenate lowered serum triglycerides to a similar extent. The hypotriglyceridemic effect of halofenate was significant only when data from noncompliant patients were discarded. Only clofibrate lowered baseline levels of plasma cholesterol. Very low density lipoproteins were decreased and low density lipoproteins were increased by clofibrate but not by halofenate. Halofenate had a marked hypouricemic effect that was greater than that of clofibrate. The hypouricemic effect of halofenate and clofibrate was paralleled by a concomitant decrease in serum bilirubin. Abnormal increases in serum creatine phosphokinase were observed with both drugs primarily in patients who had abnormal initial levels."} {"id": "PMID:177243", "title": "The pattern of spread and survival in 596 cases of breast cancer related to clinical staging and histological grade.", "content": "Carcinoma of the breast in 596 patients diagnosed between 1949 and 1966 at the Reading group of hospitals has been evaluated. All operable cases were treated by simple mastectomy and post-operative radiotherapy to the chest wall and regional nodes. Tumours were graded for malignancy either routinely or retrospectively on all patients with carcinoma simplex or scirrhous carcinoma, and the relation of grading to the subsequent development and distribution of metastases studied. Recurrence developed in 348 patients, 184 of whom suffered local recurrence. Eighty-three per cent of locally recurrent cases developed generalised metastases. The incidence of pulmonary and liver metastases was significantly increased in Grade II and III tumours compared with Grade I. Very significant differences in the survival rates between grades were noted, unfavourable to the higher grade tumours; and the influence of grading on prognosis is discussed.", "contents": "The pattern of spread and survival in 596 cases of breast cancer related to clinical staging and histological grade. Carcinoma of the breast in 596 patients diagnosed between 1949 and 1966 at the Reading group of hospitals has been evaluated. All operable cases were treated by simple mastectomy and post-operative radiotherapy to the chest wall and regional nodes. Tumours were graded for malignancy either routinely or retrospectively on all patients with carcinoma simplex or scirrhous carcinoma, and the relation of grading to the subsequent development and distribution of metastases studied. Recurrence developed in 348 patients, 184 of whom suffered local recurrence. Eighty-three per cent of locally recurrent cases developed generalised metastases. The incidence of pulmonary and liver metastases was significantly increased in Grade II and III tumours compared with Grade I. Very significant differences in the survival rates between grades were noted, unfavourable to the higher grade tumours; and the influence of grading on prognosis is discussed."} {"id": "PMID:177239", "title": "Metatropic dwarfism, the Kniest syndrome and the pseudoachondroplastic dysplasias.", "content": "Metatropic dwarfism, the Kniest syndrome, and pseudoachondroplastic dysplasia are specific chondrodystrophic disorders that have in common dysplasia of the metaphyses, epiphyses, and vertebrae. Metatropic dwarfism and the Kniest syndrome have been confused with Morquio's disease and with each other in the past, but can be easily distinguished on the basis of radiographic features, clinical features, and cartilage pathology. The pseudoachondroplastic dysplasias are associated with short limbed dwarfism and have been confused with achondroplastic dwarfism, but can be readily distinguished on the basis of the normal head, delayed age of onset, the typical radiographic features and the cartilage pathology.", "contents": "Metatropic dwarfism, the Kniest syndrome and the pseudoachondroplastic dysplasias. Metatropic dwarfism, the Kniest syndrome, and pseudoachondroplastic dysplasia are specific chondrodystrophic disorders that have in common dysplasia of the metaphyses, epiphyses, and vertebrae. Metatropic dwarfism and the Kniest syndrome have been confused with Morquio's disease and with each other in the past, but can be easily distinguished on the basis of radiographic features, clinical features, and cartilage pathology. The pseudoachondroplastic dysplasias are associated with short limbed dwarfism and have been confused with achondroplastic dwarfism, but can be readily distinguished on the basis of the normal head, delayed age of onset, the typical radiographic features and the cartilage pathology."} {"id": "PMID:177247", "title": "Negative contrast electron microscopic diagnosis of viruses of neonatal calf diarrhea.", "content": "Ninety-one cases of neonatal calf diarrhea were examined for viruses with negative contrast electron microscopy. Viruses were demonstrated in 41% of the cases. Reo-like viruses and corona-like viruses, and mixed virus populations were observed in 12%, 20% and 9%, respectively. Twenty-six of the cases were examined by negative contrast electron microscopy, and by virus isolation or by fluorescent antibody technique. There was an 81% agreement in obtained results. The disagreements resulted from the demonstration of a viral agent by negative contrast electron microscopy while the other techniques did not indicate a virus. The results suggest that negative contrast electron microscopy is a more sensitive diagnostic tool for demonstration of viruses associated with neonatal calf diarrhea than are viral isolation or the fluorescent antibody technique.", "contents": "Negative contrast electron microscopic diagnosis of viruses of neonatal calf diarrhea. Ninety-one cases of neonatal calf diarrhea were examined for viruses with negative contrast electron microscopy. Viruses were demonstrated in 41% of the cases. Reo-like viruses and corona-like viruses, and mixed virus populations were observed in 12%, 20% and 9%, respectively. Twenty-six of the cases were examined by negative contrast electron microscopy, and by virus isolation or by fluorescent antibody technique. There was an 81% agreement in obtained results. The disagreements resulted from the demonstration of a viral agent by negative contrast electron microscopy while the other techniques did not indicate a virus. The results suggest that negative contrast electron microscopy is a more sensitive diagnostic tool for demonstration of viruses associated with neonatal calf diarrhea than are viral isolation or the fluorescent antibody technique."} {"id": "PMID:177248", "title": "Serological comparison of French WD-42 enterovirus isolate with bovine winter dysentery in New York State.", "content": "Forty-eight acute and convalescent paired serums from 10 dairy cattle herds naturally infected with winter dysentery and 10 paired serums from laboratory infected heifers were tested for antibody to bovine enterovirus WD-42 which reportedly reproduced the disease syndrome in France. Only 3 naturally infected and 1 experimentally infected animals had 2-fold antibody responses. No clinical symptoms were observed in 2 steers inoculated with WD-42. Each had a 4-fold or greater antibody response to the virus. Results indicate that the winter dysentery syndrome observed in New York is produced by an agent other than WD-42 virus and that it is produced by an agent other than an enterovirus.", "contents": "Serological comparison of French WD-42 enterovirus isolate with bovine winter dysentery in New York State. Forty-eight acute and convalescent paired serums from 10 dairy cattle herds naturally infected with winter dysentery and 10 paired serums from laboratory infected heifers were tested for antibody to bovine enterovirus WD-42 which reportedly reproduced the disease syndrome in France. Only 3 naturally infected and 1 experimentally infected animals had 2-fold antibody responses. No clinical symptoms were observed in 2 steers inoculated with WD-42. Each had a 4-fold or greater antibody response to the virus. Results indicate that the winter dysentery syndrome observed in New York is produced by an agent other than WD-42 virus and that it is produced by an agent other than an enterovirus."} {"id": "PMID:177250", "title": "Increased serum calcitonin levels in bronchogenic cancer.", "content": "A study of 26 men with bronchogenic cancer demonstrated high serum calcitonin levels in 62 percent (16). Levels were particularly high in patients with small-cell cancer and adenocarcinoma. Two varieties of hypercalcitonemia have been encountered: (1) ectopic hypercalcitonemia, in which the hormone is secreted by the tumor, and (2) thyroidal hypercalcitonemia, in which the high values emanate from the thyroid gland. In several patients, serum calcitonin levels decreased following therapy for the cancer. Further studies are needed to evaluate the diagnostic value and clnical utility of serum calcitonin levels as a marker substance in bronchogenic cancer.", "contents": "Increased serum calcitonin levels in bronchogenic cancer. A study of 26 men with bronchogenic cancer demonstrated high serum calcitonin levels in 62 percent (16). Levels were particularly high in patients with small-cell cancer and adenocarcinoma. Two varieties of hypercalcitonemia have been encountered: (1) ectopic hypercalcitonemia, in which the hormone is secreted by the tumor, and (2) thyroidal hypercalcitonemia, in which the high values emanate from the thyroid gland. In several patients, serum calcitonin levels decreased following therapy for the cancer. Further studies are needed to evaluate the diagnostic value and clnical utility of serum calcitonin levels as a marker substance in bronchogenic cancer."} {"id": "PMID:177252", "title": "Mechanisms of functional loss and recovery in spinal cord damage.", "content": "Two main classes of morphological change follow trauma to central nerve fibres: (1) axonal disruption leads to total disintegration of the fibre distal (with respect to the cell body) to the lesion; (2) less severe trauma produces focal demyelination with preservation of axonal continuity. Large experimental demyelinating lesions produce complete conduction block. The histologically normal portions of the fibres, proximal and distal to the lesion, retain the ability to transmit impulses. Smaller lesions allow conduction to continue, but at a reduced velocity, and the ability of the fibres to carry long trains of impulses faithfully is impaired. All three defects of conduction contribute to functional loss. After acute transient compression of the spinal cord of the cat, demyelination increases during the first week. Evidence of remyelination appears in the third week. Inappropriately thin myelin is seen surrounding histologically normal axons. By one month, 90% of the fibres in the lesion have acquired new sheaths. Studies on single fibres have shown that the myelin is organized into segments bounded by nodes. The segments are abnormally thin and short. The myelin increases in thickness with time but thin segments are still present at 18 months. Electron microscopy shows that many of the known ultrastructural prerequisites for conduction are present in the new segments. It is not yet known, however, whether the chains of very short internodes which occur on some fibres allow conduction to be restored.", "contents": "Mechanisms of functional loss and recovery in spinal cord damage. Two main classes of morphological change follow trauma to central nerve fibres: (1) axonal disruption leads to total disintegration of the fibre distal (with respect to the cell body) to the lesion; (2) less severe trauma produces focal demyelination with preservation of axonal continuity. Large experimental demyelinating lesions produce complete conduction block. The histologically normal portions of the fibres, proximal and distal to the lesion, retain the ability to transmit impulses. Smaller lesions allow conduction to continue, but at a reduced velocity, and the ability of the fibres to carry long trains of impulses faithfully is impaired. All three defects of conduction contribute to functional loss. After acute transient compression of the spinal cord of the cat, demyelination increases during the first week. Evidence of remyelination appears in the third week. Inappropriately thin myelin is seen surrounding histologically normal axons. By one month, 90% of the fibres in the lesion have acquired new sheaths. Studies on single fibres have shown that the myelin is organized into segments bounded by nodes. The segments are abnormally thin and short. The myelin increases in thickness with time but thin segments are still present at 18 months. Electron microscopy shows that many of the known ultrastructural prerequisites for conduction are present in the new segments. It is not yet known, however, whether the chains of very short internodes which occur on some fibres allow conduction to be restored."} {"id": "PMID:177261", "title": "[Ultrastructure of the lymphocytic nucleus under the effect of phytohemagglutinin stimulation].", "content": "The author presents a review of the literature, in which he describes the blast transformation of lymphocytes, induced by lectines, as a proper model for examining the metabolic and connected with them morphological changes in cellular activation. The literature connected with the basic achievements in examining the ultrastructure of the interphase nucleus is also described. The author presents his studies on the dynamic changes, occuring in the nucleus in the course of the blast transformation, induced by phytohemagglutinin. The author found early changes in the nuclear chromatin, discovered within the first hour, using together with the ordinary double staining and the method for visualization of RNA structures (EDTA method of W. Bernar) and the method of G. Moyne for establishing DNA. It was established by means of nuclear morphometry that within the first hour the reduction of dense chromatin on account of the dispersed chromatin was 7,7%, the 24th hour was 26,0% and on the 48th hour was 26,3%. On the basis of the morphometric examination the author found also that the largest was the number of perichromatin granules in nontransformed lymphocytes of PHA-cultures. The supposition that these were B-lymphocytes was supported by analogous morphometric examination on lymphocytes obtained from the thymus and bursa Fabricius of newly shelled chickens and it was established that this number in the bursa was more than twice larger. There were three types of arrangement of the interchromatin granules: in groups, diffuse and in chains and it was found that the last type was connected with the largest number of perichromatin granules. The author discusses the possibility for a transfer of whole perichromatin granules through the nuclear pores in cases under strong stimulation such as that of phytohemagglutinin.", "contents": "[Ultrastructure of the lymphocytic nucleus under the effect of phytohemagglutinin stimulation]. The author presents a review of the literature, in which he describes the blast transformation of lymphocytes, induced by lectines, as a proper model for examining the metabolic and connected with them morphological changes in cellular activation. The literature connected with the basic achievements in examining the ultrastructure of the interphase nucleus is also described. The author presents his studies on the dynamic changes, occuring in the nucleus in the course of the blast transformation, induced by phytohemagglutinin. The author found early changes in the nuclear chromatin, discovered within the first hour, using together with the ordinary double staining and the method for visualization of RNA structures (EDTA method of W. Bernar) and the method of G. Moyne for establishing DNA. It was established by means of nuclear morphometry that within the first hour the reduction of dense chromatin on account of the dispersed chromatin was 7,7%, the 24th hour was 26,0% and on the 48th hour was 26,3%. On the basis of the morphometric examination the author found also that the largest was the number of perichromatin granules in nontransformed lymphocytes of PHA-cultures. The supposition that these were B-lymphocytes was supported by analogous morphometric examination on lymphocytes obtained from the thymus and bursa Fabricius of newly shelled chickens and it was established that this number in the bursa was more than twice larger. There were three types of arrangement of the interchromatin granules: in groups, diffuse and in chains and it was found that the last type was connected with the largest number of perichromatin granules. The author discusses the possibility for a transfer of whole perichromatin granules through the nuclear pores in cases under strong stimulation such as that of phytohemagglutinin."} {"id": "PMID:177262", "title": "[Mechanism of the antispasmogenic action of some substances that affect the 3', 5'-AMP system].", "content": "The authors carried out studies on isolated segmets of ileum with a length of 3 sm. obtained from both male and female, mature and immature guinea pigs and adult male and female rats as well as on isolated vasa deferntia, obtained from guinea pigs and rats. They examined the influence of a group of substances, known as stimulators and inhibitors of adenyl-cyclase and phosphodiesterase (isoprenaline, lithium sulfate, imidazol, theophiline and eupaverine) on the spasmogenic effects of acethylcholine (on ileum) and of noradrenaline (on vas deferens). These substances were used in doses, which were subthreshold in respect to their effect on the biogenesis and exzymic inactivation of the cyclic AMP. The authors found certain species, adult and sex differences in the spasmogenic effects of acethylcholine and noradrenaline. The examined substances lowered the spasmogenic effects of acethylcholine and noradrenaline in most of the experiments. Since the examined substance-classical means for altering the endogenous production of the cyclic AMP-show antispasmogenic effect in concentrations subthreshold for their influence on the level of the cyclic AMP, an inference is made that their inherent antispasmogenic effect is due also to a mechanism, which does not require the inclusion of the system of the cyclic AMP.", "contents": "[Mechanism of the antispasmogenic action of some substances that affect the 3', 5'-AMP system]. The authors carried out studies on isolated segmets of ileum with a length of 3 sm. obtained from both male and female, mature and immature guinea pigs and adult male and female rats as well as on isolated vasa deferntia, obtained from guinea pigs and rats. They examined the influence of a group of substances, known as stimulators and inhibitors of adenyl-cyclase and phosphodiesterase (isoprenaline, lithium sulfate, imidazol, theophiline and eupaverine) on the spasmogenic effects of acethylcholine (on ileum) and of noradrenaline (on vas deferens). These substances were used in doses, which were subthreshold in respect to their effect on the biogenesis and exzymic inactivation of the cyclic AMP. The authors found certain species, adult and sex differences in the spasmogenic effects of acethylcholine and noradrenaline. The examined substances lowered the spasmogenic effects of acethylcholine and noradrenaline in most of the experiments. Since the examined substance-classical means for altering the endogenous production of the cyclic AMP-show antispasmogenic effect in concentrations subthreshold for their influence on the level of the cyclic AMP, an inference is made that their inherent antispasmogenic effect is due also to a mechanism, which does not require the inclusion of the system of the cyclic AMP."} {"id": "PMID:177264", "title": "Basal and dibutyryl cyclic AMP-stimulated release of newly synthesized and stored growth hormone from perifused rat pituitaries.", "content": "The basal rate of pre-labeled stored 14C-labeled rat growth hormone ([14C]rGH) release from perifused rat pituitary explants is a constant fraction of pituitary GH content, suggesting random release from the storage pool. Basal release of newly synthesized [3H]rGH occurs in two phases: 1) immediate and associated with [3H]rGH synthesis, and 2) late (delayed by 60 min) and independent of concurrent [3H]rGH synthesis. Dibutyryl cyclic AMP (10(-2)M)-stimulated release of stored [14C]rGH is characterized by an initial acute rise followed by a second phase of continuous rapid release. Immediate and late release of new [3H]rGH is increased by dibutyryl cyclic AMP, and the late phase of [3H]rGH is less delayed. Simultaneous exposure of pituitary explants to [3H]alanine and [14C]leucine resulted in the release of immunoprecipitable rGH whose ratio of incorporated 3H and 14C varied with time. The observed changes suggest that after it is synthesized, a GH molecule may either be released directly or be processed into the somatotroph's storage compartment. In addition, stored GH is composed of two pools, one of which is immediately releasable. The differential incorporation of [3H]alanine and [14C]leucine into \"big\" and \"small\" rGH, together with the ability to differentially displace 3H-labeled \"big\" and 14C-labeled \"small\" rGH from the GH antibody suggest that \"big\" rGH is a heterogenous molecule including \"small\" rGH and another peptide rather than simply a dimer of \"small\" rGH.", "contents": "Basal and dibutyryl cyclic AMP-stimulated release of newly synthesized and stored growth hormone from perifused rat pituitaries. The basal rate of pre-labeled stored 14C-labeled rat growth hormone ([14C]rGH) release from perifused rat pituitary explants is a constant fraction of pituitary GH content, suggesting random release from the storage pool. Basal release of newly synthesized [3H]rGH occurs in two phases: 1) immediate and associated with [3H]rGH synthesis, and 2) late (delayed by 60 min) and independent of concurrent [3H]rGH synthesis. Dibutyryl cyclic AMP (10(-2)M)-stimulated release of stored [14C]rGH is characterized by an initial acute rise followed by a second phase of continuous rapid release. Immediate and late release of new [3H]rGH is increased by dibutyryl cyclic AMP, and the late phase of [3H]rGH is less delayed. Simultaneous exposure of pituitary explants to [3H]alanine and [14C]leucine resulted in the release of immunoprecipitable rGH whose ratio of incorporated 3H and 14C varied with time. The observed changes suggest that after it is synthesized, a GH molecule may either be released directly or be processed into the somatotroph's storage compartment. In addition, stored GH is composed of two pools, one of which is immediately releasable. The differential incorporation of [3H]alanine and [14C]leucine into \"big\" and \"small\" rGH, together with the ability to differentially displace 3H-labeled \"big\" and 14C-labeled \"small\" rGH from the GH antibody suggest that \"big\" rGH is a heterogenous molecule including \"small\" rGH and another peptide rather than simply a dimer of \"small\" rGH."} {"id": "PMID:177265", "title": "Characterization and modulation of growth hormone and prolactin binding in mouse liver.", "content": "The specific binding of 125I-labeled insulin, human hormone ([125I]hGH), bovine growth hormone ([125I]bGH), and ovine prolactin ([125I]oPRL) was studied in mouse liver membranes. [125I]hGH and [125I]oPRL bound to adult liver membranes. Pregnancy increased the specific binding of [125I]hGH but not that of [125I]oPRL. [125I]hGH was displaced from membranes of pregnant mice by hGH, oPRL, and bGH, but only by hGH and oPRL from liver membranes of nonpregnant mice. Significant specific binding of [125I]bGH was seen only in pregnancy. The binding of [125I]bGH to pregnant mouse liver membranes increased with increasing concentration of either membrane protein or [125I]bGH. Both the specific binding and dissociation of [125I]bGH were greatly influenced by the time and temperature of incubation. Binding of [125I]bGH was inhibited by growth hormones, including hGH and rat GH, and not by lactogenic hormones (various prolactins and human placental lactogen), ACTH, glucagon, or insulin. The inhibition of [125I]hGH binding by hGH and bGH, in the presence of excess (2 mug/ml) of PRL, was very similar to that seen with [125I]bGH. Scatchard plots of displacement dose-response curves obtained under steady state conditions of 4C were nonlinear and very similar with either [125I]bGH or [125I]hGH. This contrasted with the linear Scatchard plots obtained from displacement dose-response curves of either [125I]oPRL or [125I]hGH in the presence of excess (2 mug/ml) bGH. Termination of pregnancy, either naturally or by hysterectomy, reduced [125I]bGH specific binding to nonpregnant levels by 24 to 36 h. Estrogen administration did not increase [125I]bGH binding in hepatic membranes. Nonpregnant mice possess hepatic lactogen binding sites which are uninfluenced by pregnancy. GH specific binding sites are markedly augmented during pregnancy. The close correlation between the level of these sites and pregnancy suggests that they are regulated by a product of the fetoplacental unit.", "contents": "Characterization and modulation of growth hormone and prolactin binding in mouse liver. The specific binding of 125I-labeled insulin, human hormone ([125I]hGH), bovine growth hormone ([125I]bGH), and ovine prolactin ([125I]oPRL) was studied in mouse liver membranes. [125I]hGH and [125I]oPRL bound to adult liver membranes. Pregnancy increased the specific binding of [125I]hGH but not that of [125I]oPRL. [125I]hGH was displaced from membranes of pregnant mice by hGH, oPRL, and bGH, but only by hGH and oPRL from liver membranes of nonpregnant mice. Significant specific binding of [125I]bGH was seen only in pregnancy. The binding of [125I]bGH to pregnant mouse liver membranes increased with increasing concentration of either membrane protein or [125I]bGH. Both the specific binding and dissociation of [125I]bGH were greatly influenced by the time and temperature of incubation. Binding of [125I]bGH was inhibited by growth hormones, including hGH and rat GH, and not by lactogenic hormones (various prolactins and human placental lactogen), ACTH, glucagon, or insulin. The inhibition of [125I]hGH binding by hGH and bGH, in the presence of excess (2 mug/ml) of PRL, was very similar to that seen with [125I]bGH. Scatchard plots of displacement dose-response curves obtained under steady state conditions of 4C were nonlinear and very similar with either [125I]bGH or [125I]hGH. This contrasted with the linear Scatchard plots obtained from displacement dose-response curves of either [125I]oPRL or [125I]hGH in the presence of excess (2 mug/ml) bGH. Termination of pregnancy, either naturally or by hysterectomy, reduced [125I]bGH specific binding to nonpregnant levels by 24 to 36 h. Estrogen administration did not increase [125I]bGH binding in hepatic membranes. Nonpregnant mice possess hepatic lactogen binding sites which are uninfluenced by pregnancy. GH specific binding sites are markedly augmented during pregnancy. The close correlation between the level of these sites and pregnancy suggests that they are regulated by a product of the fetoplacental unit."} {"id": "PMID:177266", "title": "Capacity of immunologically purified FSH to stimulate cyclic AMP accumulation and steroidogenesis in Graafian follicles and to induce ovum maturation and ovulation in the rat.", "content": "Reference preparations of ovine follicle-stimulating hormone (NIH-FSH-S8 and S9; 10-50 mug/ml) induced ovum maturation and stimulated cyclic AMP formation, as well as progesterone and 17beta-estradiol secretion, by rat Graafian follicles in vitro. These actions of NIH-FSH were retained after immunoabsorption of any contaminating luteinizing hormone (LH) present in the preparations, by treatment with an antiserum to the beta-subunit of purified ovine LH (anti-betaLH). In contrast, the corresponding biological actions of NIH-LH-S18 (0.5-10 mug/ml) were abolished by treatment with this anti-betaLH serum. A highly purified FSH preparation (64-96 CD, 0.25 mug/ml) also triggered oocytic meiosis and increased follicular progesterone secretion in vitro. Intraperitoneal (ip) administration of anti-betaLH-treated NIH-FSH-S9 (50 mug/rat at 1430 h) consistently induced ovulation in proestrous rats in which the endogenous gonadotropin surge had been blocked by ip injection of either Nembutal (1345 h) or antiserum to the LH-releasing hormone (1200 h). Injection (ip) of anti-betaLH serum on its own into proestrous rats at 1200 h prevented ovum maturation and follicular rupture. We conclude that currently available reference preparations of ovine FSH possess the capacity to stimulate follicular adenylate cyclase, steroidogenesis, and ovum maturation in vitro, as well as ovulation in vivo, in the rat, and that this capacity cannot be attributed to contamination with material immunochemically identical with LH. However, it is inferred that the physiological triggering of ovulation and related events in this species depends principally on LH.", "contents": "Capacity of immunologically purified FSH to stimulate cyclic AMP accumulation and steroidogenesis in Graafian follicles and to induce ovum maturation and ovulation in the rat. Reference preparations of ovine follicle-stimulating hormone (NIH-FSH-S8 and S9; 10-50 mug/ml) induced ovum maturation and stimulated cyclic AMP formation, as well as progesterone and 17beta-estradiol secretion, by rat Graafian follicles in vitro. These actions of NIH-FSH were retained after immunoabsorption of any contaminating luteinizing hormone (LH) present in the preparations, by treatment with an antiserum to the beta-subunit of purified ovine LH (anti-betaLH). In contrast, the corresponding biological actions of NIH-LH-S18 (0.5-10 mug/ml) were abolished by treatment with this anti-betaLH serum. A highly purified FSH preparation (64-96 CD, 0.25 mug/ml) also triggered oocytic meiosis and increased follicular progesterone secretion in vitro. Intraperitoneal (ip) administration of anti-betaLH-treated NIH-FSH-S9 (50 mug/rat at 1430 h) consistently induced ovulation in proestrous rats in which the endogenous gonadotropin surge had been blocked by ip injection of either Nembutal (1345 h) or antiserum to the LH-releasing hormone (1200 h). Injection (ip) of anti-betaLH serum on its own into proestrous rats at 1200 h prevented ovum maturation and follicular rupture. We conclude that currently available reference preparations of ovine FSH possess the capacity to stimulate follicular adenylate cyclase, steroidogenesis, and ovum maturation in vitro, as well as ovulation in vivo, in the rat, and that this capacity cannot be attributed to contamination with material immunochemically identical with LH. However, it is inferred that the physiological triggering of ovulation and related events in this species depends principally on LH."} {"id": "PMID:177267", "title": "Comparison of the metabolism and distribution of L-triiodothyronine and triiodothyroacetic acid in the rat: a possible explanation of differential hormonal potency.", "content": "Previous studies from this laboratory have shown that nuclear displacement of triiodothyronine (T3) is more rapidly dissipated after iv injection of triiodothyroacetic acid (triac) than after equimolar doses of T3. This suggested that the discrepancy between the strong nuclear binding of triac and its relatively weak thyromimetic effect could be explained by a more rapid fractional rate of triac metabolism. To test this hypothesis, tracer studies with radioactively labeled T3 and triac were carried out in normal male Sprague-Dawley rats. Noncompartmental analysis showed that the average residence time of tracer triac in the exchangeable compartment was 5.5 h compared with 10.9 h for T3. The metabolic clearance rate of triac was 14.4 ml/h/100 g BW and of T3 17.6 ml/h/100 g. The average distribution space of triac was 78.2 ml/100 g and of T3 190.7 ml/100 g. The fraction of isotope excreted via the fecal route was 0.46 for triac and 0.41 for T3. Triac was approximately 16 times as firmly bound to plasma proteins as was T3. Isotopic studies suggested that a rapid exchange of tracer triac occurred between plasma, cytosol, and nuclei, similar to previously observed relationships for T3. Based on the daily dose of T3 and triac required to maintain a normal concentration of alpha-glycero-phosphate dehydrogenase in thyroidectomized animals, the T3:triac potency ratio was estimated to be 3.0. Our observations support the concept that a shorter duration of nuclear occupancy observed in previous experiments can be attributed to a more rapid fractional metabolism of triac and may explain the lesser hormonal effect of this compound. Since labeled triac could not be identified in nuclear extracts after the injection of isotopically labeled T3, it appears unlikely that the initiation of hormonal effects by T3 at the nuclear level is dependent on its prior conversion to triac.", "contents": "Comparison of the metabolism and distribution of L-triiodothyronine and triiodothyroacetic acid in the rat: a possible explanation of differential hormonal potency. Previous studies from this laboratory have shown that nuclear displacement of triiodothyronine (T3) is more rapidly dissipated after iv injection of triiodothyroacetic acid (triac) than after equimolar doses of T3. This suggested that the discrepancy between the strong nuclear binding of triac and its relatively weak thyromimetic effect could be explained by a more rapid fractional rate of triac metabolism. To test this hypothesis, tracer studies with radioactively labeled T3 and triac were carried out in normal male Sprague-Dawley rats. Noncompartmental analysis showed that the average residence time of tracer triac in the exchangeable compartment was 5.5 h compared with 10.9 h for T3. The metabolic clearance rate of triac was 14.4 ml/h/100 g BW and of T3 17.6 ml/h/100 g. The average distribution space of triac was 78.2 ml/100 g and of T3 190.7 ml/100 g. The fraction of isotope excreted via the fecal route was 0.46 for triac and 0.41 for T3. Triac was approximately 16 times as firmly bound to plasma proteins as was T3. Isotopic studies suggested that a rapid exchange of tracer triac occurred between plasma, cytosol, and nuclei, similar to previously observed relationships for T3. Based on the daily dose of T3 and triac required to maintain a normal concentration of alpha-glycero-phosphate dehydrogenase in thyroidectomized animals, the T3:triac potency ratio was estimated to be 3.0. Our observations support the concept that a shorter duration of nuclear occupancy observed in previous experiments can be attributed to a more rapid fractional metabolism of triac and may explain the lesser hormonal effect of this compound. Since labeled triac could not be identified in nuclear extracts after the injection of isotopically labeled T3, it appears unlikely that the initiation of hormonal effects by T3 at the nuclear level is dependent on its prior conversion to triac."} {"id": "PMID:177268", "title": "Corticoid receptors in rat brain: evidence for an aldosterone receptor.", "content": "The existence of high and low affinity mineralocorticoid-binding macromolecules (receptors) has been demonstrated in vitro in cytosols derived from the adrenalectomized rat brain by the specific binding of [3H]aldosterone (3H-A). The high-affinity aldosterone sites can be distinguished from those sites which have a higher affinity for either [3H]dexamethasone (3H-DM) or [3H]corticosterone (3H-B) on the basis of selectivity for spirolactone SC-9420 or non-radioactive A, DM, and B. The binding of 3H-A to the receptors was maximal after 2 hours of incubation of 0-4C. No significant binding of 3H-A to the receptors could be demonstrated when incubations of the radioactive ligand were performed at either 20 or 37 C, indicating that the receptor is heat-liabile. Scatchard analysis of the 3H-A binding data over a 200-fold concentration range of 3H-A indicated that there are two binding sites for aldosterone, a high affinity component (a1) with a Kd approximately equal to 1.5 X 10(-9)M and a low-affinity component (a2) with a Kd approximately equal to 6.3 X 10(-8)M. A similar study using 3H-DM as the radioactive ligand demonstrated only one site for the 3H-DM binding with a Kd = 6.2 X 10(-9)M. The presence of specific aldosterone receptors in the brain with high affinity, limited capacity, and selectivity for aldosterone suggests a possible extra-renal mechanism of action of the hormone in or mediated through the CNS.", "contents": "Corticoid receptors in rat brain: evidence for an aldosterone receptor. The existence of high and low affinity mineralocorticoid-binding macromolecules (receptors) has been demonstrated in vitro in cytosols derived from the adrenalectomized rat brain by the specific binding of [3H]aldosterone (3H-A). The high-affinity aldosterone sites can be distinguished from those sites which have a higher affinity for either [3H]dexamethasone (3H-DM) or [3H]corticosterone (3H-B) on the basis of selectivity for spirolactone SC-9420 or non-radioactive A, DM, and B. The binding of 3H-A to the receptors was maximal after 2 hours of incubation of 0-4C. No significant binding of 3H-A to the receptors could be demonstrated when incubations of the radioactive ligand were performed at either 20 or 37 C, indicating that the receptor is heat-liabile. Scatchard analysis of the 3H-A binding data over a 200-fold concentration range of 3H-A indicated that there are two binding sites for aldosterone, a high affinity component (a1) with a Kd approximately equal to 1.5 X 10(-9)M and a low-affinity component (a2) with a Kd approximately equal to 6.3 X 10(-8)M. A similar study using 3H-DM as the radioactive ligand demonstrated only one site for the 3H-DM binding with a Kd = 6.2 X 10(-9)M. The presence of specific aldosterone receptors in the brain with high affinity, limited capacity, and selectivity for aldosterone suggests a possible extra-renal mechanism of action of the hormone in or mediated through the CNS."} {"id": "PMID:177269", "title": "Androgen-uterine interaction: nuclear translocation of the estrogen receptor and induction of the synthesis of the uterine-induced protein (IP) by high concentrations of androgens in vitro but not in vivo.", "content": "High concentrations of androgens in vitro [10(-6) and 10(-7)M 5alpha-dihydrotestosterone (DHT) and testosterone (T)] translocate the estrogen receptor from cytoplasmic to the nuclear fraction of the immature rat uterus, and the androgen translocated sites are capable of eliciting the synthesis of the specific uterine \"induced protein\" (IP), formerly attributed to estrogenic compounds only. The magnitude of receptor translocation and IP synthesis induction is related to the concentration of androgen, and, at equal concentrations, DHT is more effective than T. Competitive protein-binding asssays with cell-free uterine cytosol indicate that DHT and T bind with barely detectable affinity to the cytosol estrogen receptor detectable affinity to the cytosol estrogen receptor [relative binding ability ca. 0.001% that of estradiol (E2)], and radioactive E2 uptake into whole uterus after pretreatment with androgens indicates that the androgen-translocated nuclear sites are readily filled by E2. DHT and T translocate the estrogen receptor to the nucleus in vitro, and the salt-extracted nuclear receptor is present as a 5 S (\"transformed\") receptor; however, concentrations of DHT and T that effect translocation are unable to elicit the heat-activated transformation of the estrogen receptor in cell free cytosol under conditions in which low concentrations of E2 fully transform the receptor. Under in vivo conditions, high levels of androgens (5--2,000 mug DHT or T) do not evoke any detectable translocation of the estrogen receptor and do not elicit any IP synthesis induction although uterine weight is increased (greater than 200 mug androgen) in long-term (2--3 day) assays. The analysis of androgen uptake and metabolism indicates that 500 mug or higher doses of DHT or T in vivo result in uterine concentrations of unmetabolized DHT or T equal to those seen after exposure to 5 X 10(-7) - 1 X 10(-6)M DHT or T in vitro. Hence, under conditions where in vivo and in vitro tissue uptake of androgen is equivalent, in vivo androgens are unable to affect the estrogen receptor system as is seen in vitro. These studies indicate that the in vitro and in vivo effects of androgens on the uterus are clearly different and suggest that the actions of androgens on the uterus in vivo are probably not directly mediated through the estrogen receptor system.", "contents": "Androgen-uterine interaction: nuclear translocation of the estrogen receptor and induction of the synthesis of the uterine-induced protein (IP) by high concentrations of androgens in vitro but not in vivo. High concentrations of androgens in vitro [10(-6) and 10(-7)M 5alpha-dihydrotestosterone (DHT) and testosterone (T)] translocate the estrogen receptor from cytoplasmic to the nuclear fraction of the immature rat uterus, and the androgen translocated sites are capable of eliciting the synthesis of the specific uterine \"induced protein\" (IP), formerly attributed to estrogenic compounds only. The magnitude of receptor translocation and IP synthesis induction is related to the concentration of androgen, and, at equal concentrations, DHT is more effective than T. Competitive protein-binding asssays with cell-free uterine cytosol indicate that DHT and T bind with barely detectable affinity to the cytosol estrogen receptor detectable affinity to the cytosol estrogen receptor [relative binding ability ca. 0.001% that of estradiol (E2)], and radioactive E2 uptake into whole uterus after pretreatment with androgens indicates that the androgen-translocated nuclear sites are readily filled by E2. DHT and T translocate the estrogen receptor to the nucleus in vitro, and the salt-extracted nuclear receptor is present as a 5 S (\"transformed\") receptor; however, concentrations of DHT and T that effect translocation are unable to elicit the heat-activated transformation of the estrogen receptor in cell free cytosol under conditions in which low concentrations of E2 fully transform the receptor. Under in vivo conditions, high levels of androgens (5--2,000 mug DHT or T) do not evoke any detectable translocation of the estrogen receptor and do not elicit any IP synthesis induction although uterine weight is increased (greater than 200 mug androgen) in long-term (2--3 day) assays. The analysis of androgen uptake and metabolism indicates that 500 mug or higher doses of DHT or T in vivo result in uterine concentrations of unmetabolized DHT or T equal to those seen after exposure to 5 X 10(-7) - 1 X 10(-6)M DHT or T in vitro. Hence, under conditions where in vivo and in vitro tissue uptake of androgen is equivalent, in vivo androgens are unable to affect the estrogen receptor system as is seen in vitro. These studies indicate that the in vitro and in vivo effects of androgens on the uterus are clearly different and suggest that the actions of androgens on the uterus in vivo are probably not directly mediated through the estrogen receptor system."} {"id": "PMID:177270", "title": "Studies on ACTH dynamics in cultured adenohypophyseal cells: effect of adrenalectomy or dexamethasone in vitro.", "content": "Basal or hypothalamic extract-induced ACTH or TSH secretory capacity as well as intracellular ACTH content were assessed in cultured rat adenohypophyseal cells after various pretreatments of the donor animals. Medium and intracellular ACTH or TSH were measured by radioimmunoassay. Ten-day to 2-month adrenalectomy enhanced, whereas dexamethasone pretreatment suppressed, both synthesis and secretion of ACTH in the adenohypophyseal cells. Dexamethasone may also impair the replication of the adenohypophyseal cells in vivo, as indicated by the smaller number of cells obtained per animal in the dexamethasone-treated group. No significant increase in TSH secretion was observed when adenohypophyseal cells were derived from rats fed propyl-thiouracil (PTU) for 3 weeks instead of from intact rats.", "contents": "Studies on ACTH dynamics in cultured adenohypophyseal cells: effect of adrenalectomy or dexamethasone in vitro. Basal or hypothalamic extract-induced ACTH or TSH secretory capacity as well as intracellular ACTH content were assessed in cultured rat adenohypophyseal cells after various pretreatments of the donor animals. Medium and intracellular ACTH or TSH were measured by radioimmunoassay. Ten-day to 2-month adrenalectomy enhanced, whereas dexamethasone pretreatment suppressed, both synthesis and secretion of ACTH in the adenohypophyseal cells. Dexamethasone may also impair the replication of the adenohypophyseal cells in vivo, as indicated by the smaller number of cells obtained per animal in the dexamethasone-treated group. No significant increase in TSH secretion was observed when adenohypophyseal cells were derived from rats fed propyl-thiouracil (PTU) for 3 weeks instead of from intact rats."} {"id": "PMID:177271", "title": "Regulation of estrogen receptors in ovarian-dependent rat mammary tumors. I. Effects of castration and prolactin.", "content": "The \"ovarian-dependent\" rat mammary tumors, induced by 9,10 dimethyl-1,2-benzanthracene, were assayed for their estrogen receptor content by dextran-coated charcoal adsorption and sucrose gradient ultra-centrifugation. The estradiol receptors bound estrogens with a high affinity (KD approximately 0.25 nM), limited capacity and high specificity, and sediment at 8 S in a sucrose gradient. The cytosol receptors were transferred to the nucleus after binding to estrogens either in vivo or in vitro. The tumor area regressed by 70% during the first 10 days of castration while the concentration of estradiol cytosol receptors decreased from 225 to 16 fmoles/mg of protein. Three to five days after in vivo administration of estradiol (2 mug daily) or prolactin (1 mg daily) the concentration of estrogen receptors was increased in spayed rats. In biopsy experiments, prolactin, but not estradiol, was shown to increase the estrogen receptor concentration when endogenous prolactin release was blocked by CB 154. Prolactin did not modify the intracellular distribution of the estrogen receptor or its binding affinity for estrogen. The uterine estrogen receptor sites were not modified by prolactin under the same conditions. We, therefore, suggest that in mammary tumors prolactin sensitizes the action of estrogens at the target level by increasing the concentration of their available receptor sites.", "contents": "Regulation of estrogen receptors in ovarian-dependent rat mammary tumors. I. Effects of castration and prolactin. The \"ovarian-dependent\" rat mammary tumors, induced by 9,10 dimethyl-1,2-benzanthracene, were assayed for their estrogen receptor content by dextran-coated charcoal adsorption and sucrose gradient ultra-centrifugation. The estradiol receptors bound estrogens with a high affinity (KD approximately 0.25 nM), limited capacity and high specificity, and sediment at 8 S in a sucrose gradient. The cytosol receptors were transferred to the nucleus after binding to estrogens either in vivo or in vitro. The tumor area regressed by 70% during the first 10 days of castration while the concentration of estradiol cytosol receptors decreased from 225 to 16 fmoles/mg of protein. Three to five days after in vivo administration of estradiol (2 mug daily) or prolactin (1 mg daily) the concentration of estrogen receptors was increased in spayed rats. In biopsy experiments, prolactin, but not estradiol, was shown to increase the estrogen receptor concentration when endogenous prolactin release was blocked by CB 154. Prolactin did not modify the intracellular distribution of the estrogen receptor or its binding affinity for estrogen. The uterine estrogen receptor sites were not modified by prolactin under the same conditions. We, therefore, suggest that in mammary tumors prolactin sensitizes the action of estrogens at the target level by increasing the concentration of their available receptor sites."} {"id": "PMID:177272", "title": "Effect of feeding and fasting on the early steps of glucagon action in isolated rat liver cells.", "content": "The effect of the nutritional state (fasted or fed) on the binding of glucagon and on the glucagon-stimulated cyclic AMP accumulation in the presence of theophylline was studied in isolated rat liver cells. The binding of glucagon was higher in cells from fed than in those from fasted rats at each concentration of glucagon tested between 0.1 and 36 nM. The specific binding of the hormone was about 2-fold higher in cells from fed than from fasted rats. At concentrations of glucagon between 0.1 and 2.2 nM, the accumulation of cyclic AMP in the presence of 1 mM theophylline was higher in the cells from fed rats. Furthermore, 4 times as much glucagon was required to elicit half-maximal cyclic AMP accumulation in the cells of fasted (1.47 nM) than in the cells of fed (0.35 nM) rats. These data suggest that, in isolated rat liver cells, both glucagon binding to receptor sites and glucagon-stimulated cyclic AMP levels in the presence of theophylline can be affected by the nutritional status of the animal.", "contents": "Effect of feeding and fasting on the early steps of glucagon action in isolated rat liver cells. The effect of the nutritional state (fasted or fed) on the binding of glucagon and on the glucagon-stimulated cyclic AMP accumulation in the presence of theophylline was studied in isolated rat liver cells. The binding of glucagon was higher in cells from fed than in those from fasted rats at each concentration of glucagon tested between 0.1 and 36 nM. The specific binding of the hormone was about 2-fold higher in cells from fed than from fasted rats. At concentrations of glucagon between 0.1 and 2.2 nM, the accumulation of cyclic AMP in the presence of 1 mM theophylline was higher in the cells from fed rats. Furthermore, 4 times as much glucagon was required to elicit half-maximal cyclic AMP accumulation in the cells of fasted (1.47 nM) than in the cells of fed (0.35 nM) rats. These data suggest that, in isolated rat liver cells, both glucagon binding to receptor sites and glucagon-stimulated cyclic AMP levels in the presence of theophylline can be affected by the nutritional status of the animal."} {"id": "PMID:177273", "title": "Binding of cytosol receptor-glucocorticoid complexes by isolated nuclei of glucocorticoid-responsive and nonresponsive cultured cells.", "content": "Nuclear binding of the AtT-20 cytosol receptor-glucocorticoid complex was studied in a cell-free system using nuclei from steroid-responsive (AtT-20) and nonresponsive (EPO-G1) cell lines, both of which synthesize ACTH. The AtT-20 cell line was derived from a mouse pituitary adenocarcinoma, while the EPO cell line was established from a human malignant melanoma. The nonresponsive EPO cells lacked a cytosol receptor for glucocorticoids, and, when whole cells were incubated with labeled glucocorticoid, they were unable to concentrate the steroid in their nuclei. A cell-free system using AtT-20 cytosol preincubated with labeled glucocorticoid was used to study binding by isolated nuclei. Binding to isolated nuclei from both cell lines was indistinguishable, in terms of temperature sensitivity, binding capacity, and saturability. Sucrose density gradient analyses of KCl extracts of nuclei labeled under these cell-free conditions showed 3.2-3.6 S peaks. In contrast, a 4.0 S peak was observed consistently when unreacted cytosol was analyzed on high-salt gradients, suggesting that interaction with nuclei from both cell lines caused the receptor to alter its sedimentation characteristics. These findings suggest either that all cells contain nuclear acceptor sites and that target cell responsiveness is conferred solely by the presence or absence of the cytosol receptor, or that binding sites detected in isolated nuclei may be different from those observed in intact cells and may, in fact, obscure them.", "contents": "Binding of cytosol receptor-glucocorticoid complexes by isolated nuclei of glucocorticoid-responsive and nonresponsive cultured cells. Nuclear binding of the AtT-20 cytosol receptor-glucocorticoid complex was studied in a cell-free system using nuclei from steroid-responsive (AtT-20) and nonresponsive (EPO-G1) cell lines, both of which synthesize ACTH. The AtT-20 cell line was derived from a mouse pituitary adenocarcinoma, while the EPO cell line was established from a human malignant melanoma. The nonresponsive EPO cells lacked a cytosol receptor for glucocorticoids, and, when whole cells were incubated with labeled glucocorticoid, they were unable to concentrate the steroid in their nuclei. A cell-free system using AtT-20 cytosol preincubated with labeled glucocorticoid was used to study binding by isolated nuclei. Binding to isolated nuclei from both cell lines was indistinguishable, in terms of temperature sensitivity, binding capacity, and saturability. Sucrose density gradient analyses of KCl extracts of nuclei labeled under these cell-free conditions showed 3.2-3.6 S peaks. In contrast, a 4.0 S peak was observed consistently when unreacted cytosol was analyzed on high-salt gradients, suggesting that interaction with nuclei from both cell lines caused the receptor to alter its sedimentation characteristics. These findings suggest either that all cells contain nuclear acceptor sites and that target cell responsiveness is conferred solely by the presence or absence of the cytosol receptor, or that binding sites detected in isolated nuclei may be different from those observed in intact cells and may, in fact, obscure them."} {"id": "PMID:177274", "title": "A possible role of cyclic AMP in mediating the effects of thyrotropin-releasing hormone on prolactin release and on prolactin and growth hormone synthesis in pituitary cells in culture.", "content": "Thyrotropin-releasing hormone (TRH) has 3 effects on clonal strains of rat pituitary cells in culture (GH-cells). Two long-term effects of TRH on GH-cells, which are measurable after 3 h or longer, have been previously reported; these are an increase in prolactin synthesis and a decrease in growth hormone production. We report here that TRH also stimulates the rapid release of stored intracellular prolactin. We have investigated the role of cyclic AMP as a possible mediator of the effects of TRH on GH-cells. Cyclic AMP concentrations are higher in cells treated with TRH compared with paired controls; a maximum difference of greater than 150% of control values is detected at 15 min if the incubation is performed in serum-free medium in the presence of 1 mM theophylline. The concentration of TRH required to give half-maximum increases in both prolactin release and cyclic AMP accumulation is 0.3 nM; half-maximal increases in prolactin synthesis occur at 3 nM TRH. Exogenous cyclic AMP (1 mM) causes only a slight increase in prolactin release; 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (1 mM) do not cause significant release. Phosphodiesterase inhibitors (0.3 mM theophylline, 0.03 mM isobutyl-methylxanthine) increase prolactin release but their effects on hormone synthesis are more complicated. Isobutylmethylxanthine, 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (0.4 MM) increase prolactin synthesis, but do not significantly affect growth hormone synthesis. Theophylline increases the synthesis of both hormones. Dibutyryl cyclic AMP (0.5 mM or more) increases prolactin release and both growth hormone and prolactin synthesis, but equivalent amounts of sodium butyrate have the same effects. We conclude that in GH-cells under carefully defined experimental conditions: 1) TRH causes an increase in intracellular cyclic AMP concentrations; 2) the increase in endogenous cyclic AMP and the effects of phosphodiesterase inhibitors are consistent with a model with cyclic AMP as a mediator of the effects of TRH on prolactin release; however, they do not prove this model, because the interpretation of these results depends on assumptions which may not all be valid; and 3) none of the analogs of cyclic AMP or the phosphodiesterase inhibitors tested mimic the decrease in growth hormone production caused by TRH.", "contents": "A possible role of cyclic AMP in mediating the effects of thyrotropin-releasing hormone on prolactin release and on prolactin and growth hormone synthesis in pituitary cells in culture. Thyrotropin-releasing hormone (TRH) has 3 effects on clonal strains of rat pituitary cells in culture (GH-cells). Two long-term effects of TRH on GH-cells, which are measurable after 3 h or longer, have been previously reported; these are an increase in prolactin synthesis and a decrease in growth hormone production. We report here that TRH also stimulates the rapid release of stored intracellular prolactin. We have investigated the role of cyclic AMP as a possible mediator of the effects of TRH on GH-cells. Cyclic AMP concentrations are higher in cells treated with TRH compared with paired controls; a maximum difference of greater than 150% of control values is detected at 15 min if the incubation is performed in serum-free medium in the presence of 1 mM theophylline. The concentration of TRH required to give half-maximum increases in both prolactin release and cyclic AMP accumulation is 0.3 nM; half-maximal increases in prolactin synthesis occur at 3 nM TRH. Exogenous cyclic AMP (1 mM) causes only a slight increase in prolactin release; 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (1 mM) do not cause significant release. Phosphodiesterase inhibitors (0.3 mM theophylline, 0.03 mM isobutyl-methylxanthine) increase prolactin release but their effects on hormone synthesis are more complicated. Isobutylmethylxanthine, 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (0.4 MM) increase prolactin synthesis, but do not significantly affect growth hormone synthesis. Theophylline increases the synthesis of both hormones. Dibutyryl cyclic AMP (0.5 mM or more) increases prolactin release and both growth hormone and prolactin synthesis, but equivalent amounts of sodium butyrate have the same effects. We conclude that in GH-cells under carefully defined experimental conditions: 1) TRH causes an increase in intracellular cyclic AMP concentrations; 2) the increase in endogenous cyclic AMP and the effects of phosphodiesterase inhibitors are consistent with a model with cyclic AMP as a mediator of the effects of TRH on prolactin release; however, they do not prove this model, because the interpretation of these results depends on assumptions which may not all be valid; and 3) none of the analogs of cyclic AMP or the phosphodiesterase inhibitors tested mimic the decrease in growth hormone production caused by TRH."} {"id": "PMID:177275", "title": "Dog thyroid cells in monolayer tissue culture: adenosine 3', 5'-cyclic monophosphate response to thyrotropic hormone.", "content": "A simple, rapid, and efficient method is described for establishing dog thyroid cells in tissue culture. Thyroid cell yield from a small amount of tissue (1 g) is high and viability is excellent. The adenosine 3',5-cyclic monophosphate (cAMP) response to thyrotropin (TSH) was investigated in these thyroid cells. Peak cAMP values were achieved after 10-15 min of TSH stimulation (in the presence of 0.5 mM 3-isobutyl-1-methyl-xanthine, MIX), with a subsequent decline to about half the maximal value after approximately 4 hours. This decline in cAMP concentration was associated with the development of refractoriness to TSH stimulation. Half-maximal stimulation of thyroid cell cAMP content was observed at a TSH concentration of between 1 and 2 mU/ml. Maximal cAMP values achieved were approximately 30-fold greater than basal values in the presence of MIX. The threshold of sensitivity of the cAMP response to TSH was very low, with significant stimulation being observed at a TSH concentration of 5-10 muU/ml. As determined by double reciprocal plots, the net cAMP response to TSH appeared to represent a single function over the entire TSH concentration range tested.", "contents": "Dog thyroid cells in monolayer tissue culture: adenosine 3', 5'-cyclic monophosphate response to thyrotropic hormone. A simple, rapid, and efficient method is described for establishing dog thyroid cells in tissue culture. Thyroid cell yield from a small amount of tissue (1 g) is high and viability is excellent. The adenosine 3',5-cyclic monophosphate (cAMP) response to thyrotropin (TSH) was investigated in these thyroid cells. Peak cAMP values were achieved after 10-15 min of TSH stimulation (in the presence of 0.5 mM 3-isobutyl-1-methyl-xanthine, MIX), with a subsequent decline to about half the maximal value after approximately 4 hours. This decline in cAMP concentration was associated with the development of refractoriness to TSH stimulation. Half-maximal stimulation of thyroid cell cAMP content was observed at a TSH concentration of between 1 and 2 mU/ml. Maximal cAMP values achieved were approximately 30-fold greater than basal values in the presence of MIX. The threshold of sensitivity of the cAMP response to TSH was very low, with significant stimulation being observed at a TSH concentration of 5-10 muU/ml. As determined by double reciprocal plots, the net cAMP response to TSH appeared to represent a single function over the entire TSH concentration range tested."} {"id": "PMID:177276", "title": "A receptor-like testosterone-binding protein in ovaries from estrogen-stimulated hypophysectomized immature female rats.", "content": "A soluble thermolabile protein with many characteristics of an androgen receptor has been demonstrated for the first time in the cytosol (100,000 X g supernatant) of estrogen-stimulated ovaries from hypophysectomized immature female rats (HIFR) treated with diethylstilbestrol in Silastic capsules (DESC). This binding protein is organ-specific and androgen-specific, has a high affinity with a Kd of 2.4 X 10(-9)M for testosterone, and is saturable with 2.1 X 10(-13) moles of binding sites per mg cytosol protein. The number of binding sites is linear with cytosol protein concentration and the binding protein sediments at 7-8 S on sucrose gradients. Estradiol is an effective inhibitor of testosterone binding. A role for this testosterone-binding protein as an effector of ovarian morphologic change is hypothesized.", "contents": "A receptor-like testosterone-binding protein in ovaries from estrogen-stimulated hypophysectomized immature female rats. A soluble thermolabile protein with many characteristics of an androgen receptor has been demonstrated for the first time in the cytosol (100,000 X g supernatant) of estrogen-stimulated ovaries from hypophysectomized immature female rats (HIFR) treated with diethylstilbestrol in Silastic capsules (DESC). This binding protein is organ-specific and androgen-specific, has a high affinity with a Kd of 2.4 X 10(-9)M for testosterone, and is saturable with 2.1 X 10(-13) moles of binding sites per mg cytosol protein. The number of binding sites is linear with cytosol protein concentration and the binding protein sediments at 7-8 S on sucrose gradients. Estradiol is an effective inhibitor of testosterone binding. A role for this testosterone-binding protein as an effector of ovarian morphologic change is hypothesized."} {"id": "PMID:177277", "title": "Hormonal control of renal phosphoenolpyruvate carboxykinase activity during development of the rat.", "content": "The effect of injections of hormones in utero on fetal rat kidney and liver extramitochondrial phosphoenolpyruvate carboxykinase activity has been studied. Glucagon and thyroxine induced the liber enzyme but none of the hormones tested affected the renal enzyme. In the postnatal rat, the hepatic phosphoenolpyruvate barboxykinase activity is increased after triamcinolone or thyroxine injection but only triamcinolone injection increases the activity of the kidney enzyme. It is suggested that the rise in renal phosphoenolpyruvate carboxykinase activity at about 10 days of age is due to the increase in blood corticosterone content occurring at the same age.", "contents": "Hormonal control of renal phosphoenolpyruvate carboxykinase activity during development of the rat. The effect of injections of hormones in utero on fetal rat kidney and liver extramitochondrial phosphoenolpyruvate carboxykinase activity has been studied. Glucagon and thyroxine induced the liber enzyme but none of the hormones tested affected the renal enzyme. In the postnatal rat, the hepatic phosphoenolpyruvate barboxykinase activity is increased after triamcinolone or thyroxine injection but only triamcinolone injection increases the activity of the kidney enzyme. It is suggested that the rise in renal phosphoenolpyruvate carboxykinase activity at about 10 days of age is due to the increase in blood corticosterone content occurring at the same age."} {"id": "PMID:177278", "title": "Intramicrosomal location in intestine of enzymes which synthesize complex lipid.", "content": "Smooth and rough microsomal fractions were prepared from hamster intestinal mucosa and assayed for RNA, diglyceride acyltransferase, cholinephosphotransferase and lysolecithin acyltransferase. The specific activity of cholinephosphotransferase was 4-fold more in the rough than in the smooth microsomal fractions, whereas diglyceride and lysolecithin acyltransferases were respectively 26 and 57% more active in the rough microsomal fraction. The two acyltransferases were similarly located in the microsomes and more closely corresponded to the location of dietary lipid than cholinephosphotransferase.", "contents": "Intramicrosomal location in intestine of enzymes which synthesize complex lipid. Smooth and rough microsomal fractions were prepared from hamster intestinal mucosa and assayed for RNA, diglyceride acyltransferase, cholinephosphotransferase and lysolecithin acyltransferase. The specific activity of cholinephosphotransferase was 4-fold more in the rough than in the smooth microsomal fractions, whereas diglyceride and lysolecithin acyltransferases were respectively 26 and 57% more active in the rough microsomal fraction. The two acyltransferases were similarly located in the microsomes and more closely corresponded to the location of dietary lipid than cholinephosphotransferase."} {"id": "PMID:177279", "title": "Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. I. Acute carbon-tetrachloride intoxication of rat.", "content": "In acute CCL4 intoxication of rats significantly increased activities of hepatic low-Km hexokinases, glucose-6-phosphate dehydrogenase, phosphofructokinase, aldolase A and pyruvate kinase M2 with concurrently decreased activities of glucokinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, aldolase B and pyruvate kinase L were observed. The resulting enzyme pattern was apparently different from that in dietary induction. Principal component analysis revealed that the degree of enzyme deviation in the injured liver was much greater than that in the regenerating liver after partial hepatectomy and was closer to that in fetal liver or hepatoma tissue.", "contents": "Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. I. Acute carbon-tetrachloride intoxication of rat. In acute CCL4 intoxication of rats significantly increased activities of hepatic low-Km hexokinases, glucose-6-phosphate dehydrogenase, phosphofructokinase, aldolase A and pyruvate kinase M2 with concurrently decreased activities of glucokinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, aldolase B and pyruvate kinase L were observed. The resulting enzyme pattern was apparently different from that in dietary induction. Principal component analysis revealed that the degree of enzyme deviation in the injured liver was much greater than that in the regenerating liver after partial hepatectomy and was closer to that in fetal liver or hepatoma tissue."} {"id": "PMID:177280", "title": "A reassessment of the phospholipid dependence of membrane-bound enzymes, with special reference to glucose-6-phosphatase and Na+, K+-dependent adenosine triphosphatase.", "content": "It is suggested that the specific involvement of phospholipid in either the expression or constraint of glucose-6-phosphatase activity is not conclusively established by the existing experimental evidence. The physiological significance of an apparent requirement for phosphatidylserine for Na+, K+-dependent adenosine triphosphatase activity is also questioned. The need for a critical reassessment of past conclusions in the light of present knowledge is emphasized.", "contents": "A reassessment of the phospholipid dependence of membrane-bound enzymes, with special reference to glucose-6-phosphatase and Na+, K+-dependent adenosine triphosphatase. It is suggested that the specific involvement of phospholipid in either the expression or constraint of glucose-6-phosphatase activity is not conclusively established by the existing experimental evidence. The physiological significance of an apparent requirement for phosphatidylserine for Na+, K+-dependent adenosine triphosphatase activity is also questioned. The need for a critical reassessment of past conclusions in the light of present knowledge is emphasized."} {"id": "PMID:177281", "title": "Serological detection of equid herpesvirus 1 infections of the respiratory tract.", "content": "An investigation was made of 3 serological tests (virus neutralization, complement fixation and indirect immunofluorescence), which are applicable to epidemiological studies of infections by Equid herpesvirus 1 (EHV-1). Sera from gnotobiotic foals inoculated intranasally with various strains of EHV-1 were unable in some cases to neutralize heterologous strains and these results were not consistent with the existence of clearly-defined subtypes of EHV-1, as previously proposed. The cross-reactions in complement-fixation tests paralleled those with neutralization but immunofluorescence tests were found to be both more sensitive and more broadly reactive than the other two. Complement-fixing antibodies declined more rapidly following experimental infection than did those measured by neutralization or immunofluorescence. The results are discussed in relation to the diagnosis of EHV-1 infection and the significance they may have for the epidemiology of this disease.", "contents": "Serological detection of equid herpesvirus 1 infections of the respiratory tract. An investigation was made of 3 serological tests (virus neutralization, complement fixation and indirect immunofluorescence), which are applicable to epidemiological studies of infections by Equid herpesvirus 1 (EHV-1). Sera from gnotobiotic foals inoculated intranasally with various strains of EHV-1 were unable in some cases to neutralize heterologous strains and these results were not consistent with the existence of clearly-defined subtypes of EHV-1, as previously proposed. The cross-reactions in complement-fixation tests paralleled those with neutralization but immunofluorescence tests were found to be both more sensitive and more broadly reactive than the other two. Complement-fixing antibodies declined more rapidly following experimental infection than did those measured by neutralization or immunofluorescence. The results are discussed in relation to the diagnosis of EHV-1 infection and the significance they may have for the epidemiology of this disease."} {"id": "PMID:177282", "title": "A possible correlation between lipid hydration and lipid activation of the C55-isoprenoid alcohol phosphokinase apoprotein.", "content": "1. A direct method for determining the binding of triated water to lipids is described. The experimental conditions were practically identical to those previously employed (1974) in the determination of the cofactor activities of a series of oleyl-lipids in reactivation of the C55-isoprenoid alcohol phosphokinase apoprotein. 2. Active cofactor lipids (dioleyl lecithin, sodium oleate, 1-monoolein, 1-monomyristin)bound between 2.3 and 5.3 nmol 3H2O per nmol lipid, whereas less than 0.14 nmol 3H2O were bound per nmol of the inactive lipids (1,2- and 1,3-diolein, triolein, oleyl alcohol, methyl oleate, cholesteryl oleate). 3. When exposed to 3H2O vapour, the active lipids adsorbed between 1 and 2 nmol 3H2O per nmol lipid, whereas the inactive lipids adsorbed less than 0.1 nmol 3H2O per nmol lipid. 4. The active lipid cofactor, egg lecithin, bound more than twice as much 3H2O as egg phosphatidylethanolamine which was devoid of cofactor activity in the absence of detergent. 5. Appropriately hydrated lipid polar groups are concluded to be required for an alignment with polar amino acid side chains of the enzyme apoprotein in the formation of a mixed micellar lipoprotein complex. The enzyme reaction might occur at the resulting lipoprotein/water interface.", "contents": "A possible correlation between lipid hydration and lipid activation of the C55-isoprenoid alcohol phosphokinase apoprotein. 1. A direct method for determining the binding of triated water to lipids is described. The experimental conditions were practically identical to those previously employed (1974) in the determination of the cofactor activities of a series of oleyl-lipids in reactivation of the C55-isoprenoid alcohol phosphokinase apoprotein. 2. Active cofactor lipids (dioleyl lecithin, sodium oleate, 1-monoolein, 1-monomyristin)bound between 2.3 and 5.3 nmol 3H2O per nmol lipid, whereas less than 0.14 nmol 3H2O were bound per nmol of the inactive lipids (1,2- and 1,3-diolein, triolein, oleyl alcohol, methyl oleate, cholesteryl oleate). 3. When exposed to 3H2O vapour, the active lipids adsorbed between 1 and 2 nmol 3H2O per nmol lipid, whereas the inactive lipids adsorbed less than 0.1 nmol 3H2O per nmol lipid. 4. The active lipid cofactor, egg lecithin, bound more than twice as much 3H2O as egg phosphatidylethanolamine which was devoid of cofactor activity in the absence of detergent. 5. Appropriately hydrated lipid polar groups are concluded to be required for an alignment with polar amino acid side chains of the enzyme apoprotein in the formation of a mixed micellar lipoprotein complex. The enzyme reaction might occur at the resulting lipoprotein/water interface."} {"id": "PMID:177283", "title": "Homoserine kinase from Escherichia coli K12.", "content": "Homoserine kinase was purified to apparent homogeneity from a derepressed strain of Escherichia coli K12, using standard fractionation techniques. It is a dimer (Mr = 60000) composed of apparently identical polypeptide chains (Mr = 29000). Its amino acid composition and N-terminal sequence have been determined. L-Threonine is a competitive inhibitor of the substrate L-homoserine; this inhibition is straighforward and shows no sign of co-operativity. Evidence is presented that homoserine and threonine bind to the same site of this non-allosteric enzyme. The binding of homoserine and threonine can also be studied by difference spectroscopy; the latter studies reveal an unexpected effect of magnesium ions, which might be the basis for the unusual high Mg2+ requirement for optimal enzyme reaction.", "contents": "Homoserine kinase from Escherichia coli K12. Homoserine kinase was purified to apparent homogeneity from a derepressed strain of Escherichia coli K12, using standard fractionation techniques. It is a dimer (Mr = 60000) composed of apparently identical polypeptide chains (Mr = 29000). Its amino acid composition and N-terminal sequence have been determined. L-Threonine is a competitive inhibitor of the substrate L-homoserine; this inhibition is straighforward and shows no sign of co-operativity. Evidence is presented that homoserine and threonine bind to the same site of this non-allosteric enzyme. The binding of homoserine and threonine can also be studied by difference spectroscopy; the latter studies reveal an unexpected effect of magnesium ions, which might be the basis for the unusual high Mg2+ requirement for optimal enzyme reaction."} {"id": "PMID:177284", "title": "Phosphorylation of microtubule-associated proteins.", "content": "1. Tubulin is not an adenosine-3':5'-monophosphate-dependent (cyclic-AMP-dependent) protein kinase. Both entities have been clearly separated by sucrose gradient ultracentrifugation. With a tubulin preparation obtained by the polymerization-depolymerization technique protein kinase had a sedimentation coefficient of 8.7 S whereas tubulin sedimented with 6.4 S. After preincubation with both cyclic AMP and histone the kinase dissociated into its catalytic subunit with a sedimentation coefficient of 3.4 S. 2. Tubulin prepared by the polymerization-depolymerization technique was neither phosphorylated in vivo nor in vitro. On the contrary if this preparation was further purified by the Weisenberg's procedure (DEAE-Sephadex batch absorption) before incubation with [gamma-32 P]ATP, phosphorylation occurred. Thus, phosphorylation depended on the method used to purify tubulin i.e. was likely to an an artefact.", "contents": "Phosphorylation of microtubule-associated proteins. 1. Tubulin is not an adenosine-3':5'-monophosphate-dependent (cyclic-AMP-dependent) protein kinase. Both entities have been clearly separated by sucrose gradient ultracentrifugation. With a tubulin preparation obtained by the polymerization-depolymerization technique protein kinase had a sedimentation coefficient of 8.7 S whereas tubulin sedimented with 6.4 S. After preincubation with both cyclic AMP and histone the kinase dissociated into its catalytic subunit with a sedimentation coefficient of 3.4 S. 2. Tubulin prepared by the polymerization-depolymerization technique was neither phosphorylated in vivo nor in vitro. On the contrary if this preparation was further purified by the Weisenberg's procedure (DEAE-Sephadex batch absorption) before incubation with [gamma-32 P]ATP, phosphorylation occurred. Thus, phosphorylation depended on the method used to purify tubulin i.e. was likely to an an artefact."} {"id": "PMID:177285", "title": "Conformational changes associated with transient activation of phosphorylase in glycogen particles. Studies using activity, electron-spin-resonance and phosphorus-nuclear-magnetic-resonance measurements.", "content": "1. Calcium-dependent transient phosphorylation of phorphorylase b has been monitored in a rabbit muscle glycogen particle fraction. Using a phosphorus nuclear magnetic resonance assay, the changes in concentrations of small phosphate-containing metabolites associated with this event have been measured. In addition, the conformation of phosphorylase has been monitored during transient activation by observing changes in the electron spin resonance signal from added spin-labelled phosphorylase. 2. The transient activation was associated with a loss of glucose-6-phosphate from phosphorylase b; newly formed phosphorylase a binds the nucleotides ADP, AMP, or IMP. Because of the fast interconversion of these nucleotides the species bound to phosphorylase a change throughout the process. 3. Lowering the [Mg2+] : [Ca2+] ratio during transient activation causes accumulation of ADP. Electron spin resonance data from spin-labelled phosphorylase shows that, under these conditions, ADP binding to phosphorylase a is potentiated. 4. Calcium-dependent activation in the glycogen particle fraction is compared to the activation of phosphorylase in vivo.", "contents": "Conformational changes associated with transient activation of phosphorylase in glycogen particles. Studies using activity, electron-spin-resonance and phosphorus-nuclear-magnetic-resonance measurements. 1. Calcium-dependent transient phosphorylation of phorphorylase b has been monitored in a rabbit muscle glycogen particle fraction. Using a phosphorus nuclear magnetic resonance assay, the changes in concentrations of small phosphate-containing metabolites associated with this event have been measured. In addition, the conformation of phosphorylase has been monitored during transient activation by observing changes in the electron spin resonance signal from added spin-labelled phosphorylase. 2. The transient activation was associated with a loss of glucose-6-phosphate from phosphorylase b; newly formed phosphorylase a binds the nucleotides ADP, AMP, or IMP. Because of the fast interconversion of these nucleotides the species bound to phosphorylase a change throughout the process. 3. Lowering the [Mg2+] : [Ca2+] ratio during transient activation causes accumulation of ADP. Electron spin resonance data from spin-labelled phosphorylase shows that, under these conditions, ADP binding to phosphorylase a is potentiated. 4. Calcium-dependent activation in the glycogen particle fraction is compared to the activation of phosphorylase in vivo."} {"id": "PMID:177286", "title": "Spin-labelled AMP - an activator of phosphorylase.", "content": "1. A spin-labelled AMP derivative and its diamagnetic analogue activate phosphorylase b in the same way, but do not activate phosphorylase a. 2. The electron-spin-resonance spectra of the spin-labelled AMP derivative bound to phosphorylase b and a have \"powderlike\" characteristics indicating that the spin label is immobilised on the protein. From changes in the electron-spin-resonance spectrum of spin-labelled AMP as phosphorylase b or a is added, the dissociation constants were calculated. 3. The interactions of spin-labelled AMP and the diamagnetic analogue with phosphorylase b and a have been monitored by observing changes in the spectral properties of fluorescent and spin-label probes covalently attached to the enzyme. 4. The dissociation constants of spin-labelled AMP and phosphorylase b or a are 175 +/- 25 muM and 15 +/- 5 muM respectively. Similar dissociation constants are obtained for the diamagnetic analogue. The effect of these AMP derivatives on the covalently attached probe groups and on phosphorylase activity is compared to the effect of AMP and IMP.", "contents": "Spin-labelled AMP - an activator of phosphorylase. 1. A spin-labelled AMP derivative and its diamagnetic analogue activate phosphorylase b in the same way, but do not activate phosphorylase a. 2. The electron-spin-resonance spectra of the spin-labelled AMP derivative bound to phosphorylase b and a have \"powderlike\" characteristics indicating that the spin label is immobilised on the protein. From changes in the electron-spin-resonance spectrum of spin-labelled AMP as phosphorylase b or a is added, the dissociation constants were calculated. 3. The interactions of spin-labelled AMP and the diamagnetic analogue with phosphorylase b and a have been monitored by observing changes in the spectral properties of fluorescent and spin-label probes covalently attached to the enzyme. 4. The dissociation constants of spin-labelled AMP and phosphorylase b or a are 175 +/- 25 muM and 15 +/- 5 muM respectively. Similar dissociation constants are obtained for the diamagnetic analogue. The effect of these AMP derivatives on the covalently attached probe groups and on phosphorylase activity is compared to the effect of AMP and IMP."} {"id": "PMID:177287", "title": "Gangliosides of hepatoma 27, normal and regenerating rat liver.", "content": "The highly malignant rat hepatoma 27 was found to have increased amounts of lipid-bound sialic acid as compared with normal liver whereas in regenerating liver the lipid-bound sialic acid level was reduced. In contrast to the liver the hepatoma contained higher amounts of disialogangliosides and no trisialogangliosides, which are abundant in the liver. The main disialoganglioside of the hepatoma had no analogue among the liver gangliosides and was identified as Gal-GalNAc(AcNeu-AcNeu)-Glc-Cer (GD1b), which in other tissues is known to be a precursor of trisialogangliosides. These findings may be explained by a reduced activity of glycosyltransferases in the hepatoma and apparently do not simply reflect differences in growth rate since the ganglioside pattern of regenerating rat liver was not altered significantly in comparison with the liver. Liver and hepatoma microsomes were found to be enriched in gangliosides as compared with whole cells, liver mitochondria were slightly poorer, while the ganglioside level of hepatoma mitochondria was much higher than that of the hepatoma cells. It thus appears that the existing image of the plasma membranes as the only sites of high ganglioside concentration may not hold true for weakly differentiated hepatomas of high malignancy.", "contents": "Gangliosides of hepatoma 27, normal and regenerating rat liver. The highly malignant rat hepatoma 27 was found to have increased amounts of lipid-bound sialic acid as compared with normal liver whereas in regenerating liver the lipid-bound sialic acid level was reduced. In contrast to the liver the hepatoma contained higher amounts of disialogangliosides and no trisialogangliosides, which are abundant in the liver. The main disialoganglioside of the hepatoma had no analogue among the liver gangliosides and was identified as Gal-GalNAc(AcNeu-AcNeu)-Glc-Cer (GD1b), which in other tissues is known to be a precursor of trisialogangliosides. These findings may be explained by a reduced activity of glycosyltransferases in the hepatoma and apparently do not simply reflect differences in growth rate since the ganglioside pattern of regenerating rat liver was not altered significantly in comparison with the liver. Liver and hepatoma microsomes were found to be enriched in gangliosides as compared with whole cells, liver mitochondria were slightly poorer, while the ganglioside level of hepatoma mitochondria was much higher than that of the hepatoma cells. It thus appears that the existing image of the plasma membranes as the only sites of high ganglioside concentration may not hold true for weakly differentiated hepatomas of high malignancy."} {"id": "PMID:177288", "title": "Horse-liver alcohol dehydrogenase and Pseudomonas testosteroni 3(17)beta-hydroxysteroid dehydrogenase transfer epimeric hydrogens from NADH to 17beta-hydroxy-5alpha-androstan-3-one. An exception to one of the Alworth-Bentley rules.", "content": "In the reduction of 17beta-hydroxy-5alpha-androstan-3-one to the 3beta-alcohol, horse liver alcohol dehydrogenase utilizes the 4-pro-R hydrogen of NADH whereas the 3(17)beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni utulized the 4-pro-S hydrogen. These observations provide an exception to the rule proposed by Alworth and Bentley that with regard to the paired methylene hydrogens at C-4 of NADH and NADPH \"the stereospecificity of a particular reaction is fixed and does not vary with the source of the enzyme preparation\". It is also apparent that for these two enzymes, the selection of the side of NADH from which hydride is transferred to substrate cannot in both cases be dictated by the \"best fit\" of substrate and cofactor.", "contents": "Horse-liver alcohol dehydrogenase and Pseudomonas testosteroni 3(17)beta-hydroxysteroid dehydrogenase transfer epimeric hydrogens from NADH to 17beta-hydroxy-5alpha-androstan-3-one. An exception to one of the Alworth-Bentley rules. In the reduction of 17beta-hydroxy-5alpha-androstan-3-one to the 3beta-alcohol, horse liver alcohol dehydrogenase utilizes the 4-pro-R hydrogen of NADH whereas the 3(17)beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni utulized the 4-pro-S hydrogen. These observations provide an exception to the rule proposed by Alworth and Bentley that with regard to the paired methylene hydrogens at C-4 of NADH and NADPH \"the stereospecificity of a particular reaction is fixed and does not vary with the source of the enzyme preparation\". It is also apparent that for these two enzymes, the selection of the side of NADH from which hydride is transferred to substrate cannot in both cases be dictated by the \"best fit\" of substrate and cofactor."} {"id": "PMID:177292", "title": "Urinary excretion of adenosine 3'5' monophosphate in vitamin D deficiency.", "content": "Urinary cyclic adenosine 3'5' monophosphate (AMP) excretion has been determined by radioimmunoassay in children with rickets and in control children. Cyclic AMP was greatly increased in children with rickets. The excretion of cyclic AMP correlated significantly with parathyroid hormone levels (PTH) and alkaline phosphatase, but not with age, calcaemia and serum inorganic phosphate. Calcium infusion led to a decrease in the excretion of cyclic AMP. The data are consistent with following hypothesis. During vitamin D deficiency, high PTH levels can increase the renal excretion of cyclic AMP. The effects of PTH on bone resorption fail to maintain the levels of serum calcium due to the lack of vitamin D. The mechanism by which the secondary hyperparathyroidism develops during vitamin D deficiency remains to be investigated.", "contents": "Urinary excretion of adenosine 3'5' monophosphate in vitamin D deficiency. Urinary cyclic adenosine 3'5' monophosphate (AMP) excretion has been determined by radioimmunoassay in children with rickets and in control children. Cyclic AMP was greatly increased in children with rickets. The excretion of cyclic AMP correlated significantly with parathyroid hormone levels (PTH) and alkaline phosphatase, but not with age, calcaemia and serum inorganic phosphate. Calcium infusion led to a decrease in the excretion of cyclic AMP. The data are consistent with following hypothesis. During vitamin D deficiency, high PTH levels can increase the renal excretion of cyclic AMP. The effects of PTH on bone resorption fail to maintain the levels of serum calcium due to the lack of vitamin D. The mechanism by which the secondary hyperparathyroidism develops during vitamin D deficiency remains to be investigated."} {"id": "PMID:177293", "title": "Effects of dopamine on kidney function and on the adenyl cyclase phosphodiesterase system in man.", "content": "Clearance studies were made to determine the influence of intravenous infusions of dopamine (between 2.5 and 3.5 mug.kg.-1min.-1) on renal function and on the adenyl cyclase phosphodiesterase system in eleven patients with chronic renal disease. Glomerular filtration rate (+ 19%), effective renal plasma flow )+ 29%), sodium (+ 199%) and potassium (+ 40%) clearances were significantly increased. These effects were associated with a stimulation of the adenyl cyclase phosphodiesterase system demonstrated by an increase of cyclic adenosine 3'5'-monophosphate in plasma and urine. The results suggest that dopamine probably affects renal function by activating the adenyl cyclase phosphodiesterase system.", "contents": "Effects of dopamine on kidney function and on the adenyl cyclase phosphodiesterase system in man. Clearance studies were made to determine the influence of intravenous infusions of dopamine (between 2.5 and 3.5 mug.kg.-1min.-1) on renal function and on the adenyl cyclase phosphodiesterase system in eleven patients with chronic renal disease. Glomerular filtration rate (+ 19%), effective renal plasma flow )+ 29%), sodium (+ 199%) and potassium (+ 40%) clearances were significantly increased. These effects were associated with a stimulation of the adenyl cyclase phosphodiesterase system demonstrated by an increase of cyclic adenosine 3'5'-monophosphate in plasma and urine. The results suggest that dopamine probably affects renal function by activating the adenyl cyclase phosphodiesterase system."} {"id": "PMID:177294", "title": "The metabolism of low density lipoprotein in endogenous hypertriglyceridaemia.", "content": "The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis.", "contents": "The metabolism of low density lipoprotein in endogenous hypertriglyceridaemia. The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis."} {"id": "PMID:177295", "title": "Lipids and lipoproteins in chronic uraemia. A study of the influence of regular haemodialysis.", "content": "Plasma lipids and lipoproteins were studied in a group of chronic uraemia patients some of whom were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patient. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.", "contents": "Lipids and lipoproteins in chronic uraemia. A study of the influence of regular haemodialysis. Plasma lipids and lipoproteins were studied in a group of chronic uraemia patients some of whom were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patient. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia."} {"id": "PMID:177296", "title": "Metabolism of very low density lipoproteins in hyperlipidaemia: studies of apolipoprotein B kinetics in man.", "content": "The metabolism of very low density lipoprotein-B (VLDL-B) peptide was studied in nineteen subjects with endogenous hypertriglyceridaemia (Types V, IV and IIb), three patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL-B peptide were followed. The mean turnover rate of VLDL-B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL-B peptide. A significant positive correlation was found between the turnover rate of VLDL-B peptide and VLDL-triglyceride concentration in the whole series. It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in some patients whereas a reduced clearance is the determining factor in others.", "contents": "Metabolism of very low density lipoproteins in hyperlipidaemia: studies of apolipoprotein B kinetics in man. The metabolism of very low density lipoprotein-B (VLDL-B) peptide was studied in nineteen subjects with endogenous hypertriglyceridaemia (Types V, IV and IIb), three patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL-B peptide were followed. The mean turnover rate of VLDL-B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL-B peptide. A significant positive correlation was found between the turnover rate of VLDL-B peptide and VLDL-triglyceride concentration in the whole series. It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in some patients whereas a reduced clearance is the determining factor in others."} {"id": "PMID:177297", "title": "Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid.", "content": "Stimulation of the nigro-neostriatal or mesolimbic dopamine pathway results in a stimulus dependent increase in the accumulation of dihydroxyphenylacetic acid (DOPAC) in the neostriatum and olfactory tubercles, respectively. A block of impulse flow induced pharamacologically by administration of gamma-butyrolactone or by placement of a lesion in the dopamine pathway results in a decrease in the steady state levels of DOPAC. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce a predictable change in the brain levels of DOPAC. Drugs which increase impulse flow in nigro-neostriatal or mesolimbic dopamine neurons increase DOPAC levels in the striatum and olfactory tubercles and drugs which reduce impulse flow cause a reduction in DOPAC. Pargyline, a monoamine oxidase inhibitor, causes a rapid depletion of striatal DOPAC suggesting that this metabolite is rapidly cleared from the brain. Administration of benztropine, a potent inhibitor of dopamine reuptake, causes a significant decrease in striatal DOPAC and partially prevents the stimulus-induced increase in the accumulation of DOPAC. These observations together with the finding that about 85% of the DOPAC in the striatum disappears when the dopamine neurons in the nigro-neostriatal pathway are destroyed suggests that the majority of striatal DOPAC is formed within the dopaminergic neurons and may reflect the metabolism of dopamine which has been released and recaptured. We conclude that short-term changes in brain levels of DOPAC appear to provide a useful index of alterations in the functional activity of central dopaminergic neurons.", "contents": "Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid. Stimulation of the nigro-neostriatal or mesolimbic dopamine pathway results in a stimulus dependent increase in the accumulation of dihydroxyphenylacetic acid (DOPAC) in the neostriatum and olfactory tubercles, respectively. A block of impulse flow induced pharamacologically by administration of gamma-butyrolactone or by placement of a lesion in the dopamine pathway results in a decrease in the steady state levels of DOPAC. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce a predictable change in the brain levels of DOPAC. Drugs which increase impulse flow in nigro-neostriatal or mesolimbic dopamine neurons increase DOPAC levels in the striatum and olfactory tubercles and drugs which reduce impulse flow cause a reduction in DOPAC. Pargyline, a monoamine oxidase inhibitor, causes a rapid depletion of striatal DOPAC suggesting that this metabolite is rapidly cleared from the brain. Administration of benztropine, a potent inhibitor of dopamine reuptake, causes a significant decrease in striatal DOPAC and partially prevents the stimulus-induced increase in the accumulation of DOPAC. These observations together with the finding that about 85% of the DOPAC in the striatum disappears when the dopamine neurons in the nigro-neostriatal pathway are destroyed suggests that the majority of striatal DOPAC is formed within the dopaminergic neurons and may reflect the metabolism of dopamine which has been released and recaptured. We conclude that short-term changes in brain levels of DOPAC appear to provide a useful index of alterations in the functional activity of central dopaminergic neurons."} {"id": "PMID:177298", "title": "Automatic registration of behaviour related to dopamine and noradrenaline transmission.", "content": "In a search for behavioural tests where certain behaviours related to dopamine and noradrenaline transmission can be recorded automatically we have developed and tested an automatic version of the hole board. The test measures two behaviour variables: the open field variable defined as the number of interruptions of photocell beams symmetrically covering an open field area and the 'hole' variable, defined as the number of head-dips into holes recorded by photocell beams positioned underneath the floor of the cage. The method was evaluated by observations of the rats concomitant with the automatic registrations. The animals were tested on dopamine agonistic drugs, which were found to decrease the 'hole' counts and cause an increase in the open field counts as compared to saline injected controls. d-Amphetamine which is known to increase the release of dopamine as well as of noradrenaline caused an increase in both the open field counts and the 'hole' counts. The increase in 'hole' counts caused by d-amphetamine was reduced when the animals were pretreated with a dopamine-beta-hydroxylase inhibitor (FLA 63) or a noradrenaline receptor blocker (phenoxybenzamine). These results suggests that the increase in the 'hole' variable was related to an increased noradrenaline transmission while the increase in the open field variable was related to an increased dopamine transmission. The lowest dose of apomorphine caused a behavioural inhibition which may be explained by a preferential stimulation of dopamine autoreceptors.", "contents": "Automatic registration of behaviour related to dopamine and noradrenaline transmission. In a search for behavioural tests where certain behaviours related to dopamine and noradrenaline transmission can be recorded automatically we have developed and tested an automatic version of the hole board. The test measures two behaviour variables: the open field variable defined as the number of interruptions of photocell beams symmetrically covering an open field area and the 'hole' variable, defined as the number of head-dips into holes recorded by photocell beams positioned underneath the floor of the cage. The method was evaluated by observations of the rats concomitant with the automatic registrations. The animals were tested on dopamine agonistic drugs, which were found to decrease the 'hole' counts and cause an increase in the open field counts as compared to saline injected controls. d-Amphetamine which is known to increase the release of dopamine as well as of noradrenaline caused an increase in both the open field counts and the 'hole' counts. The increase in 'hole' counts caused by d-amphetamine was reduced when the animals were pretreated with a dopamine-beta-hydroxylase inhibitor (FLA 63) or a noradrenaline receptor blocker (phenoxybenzamine). These results suggests that the increase in the 'hole' variable was related to an increased noradrenaline transmission while the increase in the open field variable was related to an increased dopamine transmission. The lowest dose of apomorphine caused a behavioural inhibition which may be explained by a preferential stimulation of dopamine autoreceptors."} {"id": "PMID:177299", "title": "An analysis of the mode of action of carbachol on the chick biventer cervicis nerve--muscle preparation.", "content": "The mechanism of contracture evoked by carbachol in the isolated chick biventer cervicis nerve--muscle preparation was studied. At concentrations lower than 11 muM, carbachol progressively induced contracture at a rate much slower than did acetylcholine. A spontaneous increase of the response to carbachol, but not to acetylcholine, was observed 2-4 hr after isolation of the muscle. By contrast, no change of the response occurred in the denervated muscle. Anticholinesterase treatment shifted the dose-response curve for carbachol markedly to the left as far as the contracture attained after 4-6 min incubation was concerned. The shift was much less marked for the dose-response curve plotted against the initial rate of response defined as the contracture obtained after 1 min incubation. No enhancement of response was detected by inhibition of acetylcholinesterase in the denervated muscle. beta-Bungarotoxin which blocked neuromuscular transmission within 30 min, caused a transient enhancement of the response to carbachol. After 2-3 hr treatment, however, the spontaneous increase of response to carbachol was counteracted by the toxin. No potentiation of the response by anticholinesterase agents was observed after toxin treatment. When added in the presence of physostigmine or echothiophate, beta-bungarotoxin reduced the response to carbachol to the control level in 2 hr. The response to carbachol in the muscle treated with alpha-bungarotoxin and washed subsequently was also not potentiated by anticholinesterase treatment. Repetitive nerve stimulation in the presence of hemicholinium-3 caused a neuromuscular blockade but did not appreciably antagonize the response to carbachol more than that to acetylcholine either in the absence or presence of physotigmine. When calcium ion in the medium was decreased from 2.7 to 0.54 mM, ther response to nerve stimulation was nearly completely inhibited, but the response to carbachol was not affected and could still be potentiated by anticholinesterase. It is concluded that carbachol has both direct and indirect effects on the chick biventer cervicis muscle. At a low concentration, particularly in the presence of an anticholinesterase and if sufficient time of incubation is allowed, the indirect effect caused by release of acetylcholine may become more prominent than the direct action on the post-synaptic receptor. Both the mechanism and the store of acetylcholine for this indirect action appear to be different from those for the nerve impulse.", "contents": "An analysis of the mode of action of carbachol on the chick biventer cervicis nerve--muscle preparation. The mechanism of contracture evoked by carbachol in the isolated chick biventer cervicis nerve--muscle preparation was studied. At concentrations lower than 11 muM, carbachol progressively induced contracture at a rate much slower than did acetylcholine. A spontaneous increase of the response to carbachol, but not to acetylcholine, was observed 2-4 hr after isolation of the muscle. By contrast, no change of the response occurred in the denervated muscle. Anticholinesterase treatment shifted the dose-response curve for carbachol markedly to the left as far as the contracture attained after 4-6 min incubation was concerned. The shift was much less marked for the dose-response curve plotted against the initial rate of response defined as the contracture obtained after 1 min incubation. No enhancement of response was detected by inhibition of acetylcholinesterase in the denervated muscle. beta-Bungarotoxin which blocked neuromuscular transmission within 30 min, caused a transient enhancement of the response to carbachol. After 2-3 hr treatment, however, the spontaneous increase of response to carbachol was counteracted by the toxin. No potentiation of the response by anticholinesterase agents was observed after toxin treatment. When added in the presence of physostigmine or echothiophate, beta-bungarotoxin reduced the response to carbachol to the control level in 2 hr. The response to carbachol in the muscle treated with alpha-bungarotoxin and washed subsequently was also not potentiated by anticholinesterase treatment. Repetitive nerve stimulation in the presence of hemicholinium-3 caused a neuromuscular blockade but did not appreciably antagonize the response to carbachol more than that to acetylcholine either in the absence or presence of physotigmine. When calcium ion in the medium was decreased from 2.7 to 0.54 mM, ther response to nerve stimulation was nearly completely inhibited, but the response to carbachol was not affected and could still be potentiated by anticholinesterase. It is concluded that carbachol has both direct and indirect effects on the chick biventer cervicis muscle. At a low concentration, particularly in the presence of an anticholinesterase and if sufficient time of incubation is allowed, the indirect effect caused by release of acetylcholine may become more prominent than the direct action on the post-synaptic receptor. Both the mechanism and the store of acetylcholine for this indirect action appear to be different from those for the nerve impulse."} {"id": "PMID:177300", "title": "Effects of derivatives of cyclic amp and cyclic gmp on contraction force of cat papillary muscles.", "content": "Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (dbcAMP) at varying concentrations as low as 1 X 10(-4)M. A positive inotropic effect was observed with all concentrations of dbcAMP. Concomitant administration of 5 X 10(-4)M monobutyryl guanosine 3',5'-monophosphate (mbcGMP) and 1-2 X 10(-4)M dbcAMP prevented the inotropic response observed when dbcAMP was used alone. When higher doses of dbcAMP were used (5 X 10(-4) M, 10 X 10(-4) M), there was no significant difference in the inotropic response seen between control tissues and papillary muscles pretreated with mbcGMP.", "contents": "Effects of derivatives of cyclic amp and cyclic gmp on contraction force of cat papillary muscles. Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (dbcAMP) at varying concentrations as low as 1 X 10(-4)M. A positive inotropic effect was observed with all concentrations of dbcAMP. Concomitant administration of 5 X 10(-4)M monobutyryl guanosine 3',5'-monophosphate (mbcGMP) and 1-2 X 10(-4)M dbcAMP prevented the inotropic response observed when dbcAMP was used alone. When higher doses of dbcAMP were used (5 X 10(-4) M, 10 X 10(-4) M), there was no significant difference in the inotropic response seen between control tissues and papillary muscles pretreated with mbcGMP."} {"id": "PMID:177317", "title": "Model for skeletal resistance to vitamin D in renal failure.", "content": "Chronic renal disease in man and animals is associated with disturbances in calcium homeostasis which are resistant to vitamin D-therapy. Partially nephrectomized and intact rats were used to evaluate the effect of uremia on the response of bone to vitamin D. Serum calcium, serum phosphorus and blood urea nitrogen levels were higher in uremic rats than in intact rats, both given vitamin D. Metaphyseal bone in uremic rats was resistant to vitamin D-induced bone resorption; osteoblasts and osteocytes appeared less active ultrastructurally and osteoclass were infrequent. Calcitonin synthesis and release evaluated electron microscopically was greater in uremic rats. It is suggested that the altered response of bone to vitamin D in uremic rats was due in part to elevated serum phosphorus and increased calcitonin release. The present model does not refute experimental and clinical data that metabolism of vitamin D is altered in renal disease. It does, however, emphasize that in chronic renal failure other parameters (phosphorus levels, calcitonin release, uremia) are operating which may influence end organ response to pharmacologic doses of vitamin D. The partially nephrectomized rat may be a useful model for evaluating end-organ resistance to vitamin D in uremia.", "contents": "Model for skeletal resistance to vitamin D in renal failure. Chronic renal disease in man and animals is associated with disturbances in calcium homeostasis which are resistant to vitamin D-therapy. Partially nephrectomized and intact rats were used to evaluate the effect of uremia on the response of bone to vitamin D. Serum calcium, serum phosphorus and blood urea nitrogen levels were higher in uremic rats than in intact rats, both given vitamin D. Metaphyseal bone in uremic rats was resistant to vitamin D-induced bone resorption; osteoblasts and osteocytes appeared less active ultrastructurally and osteoclass were infrequent. Calcitonin synthesis and release evaluated electron microscopically was greater in uremic rats. It is suggested that the altered response of bone to vitamin D in uremic rats was due in part to elevated serum phosphorus and increased calcitonin release. The present model does not refute experimental and clinical data that metabolism of vitamin D is altered in renal disease. It does, however, emphasize that in chronic renal failure other parameters (phosphorus levels, calcitonin release, uremia) are operating which may influence end organ response to pharmacologic doses of vitamin D. The partially nephrectomized rat may be a useful model for evaluating end-organ resistance to vitamin D in uremia."} {"id": "PMID:177318", "title": "Potassium, neuroglia, and oxidative metabolism in central gray matter.", "content": "Reviewed is the author's investigation of potassium in extracellular fluid of cerebral neocortex and spinal cord determined with ion-selective microelectrodes, and of oxidative metabolism monitored by fluorometric determination of intramitochondrial NADH in intact cortex. When gray matter is excited by afferent input, or by direct electrical stimulation, the logarithm of the rise of extracellular potassium concentration ([K+]0), the sustained shift of electrical potential, and the response of oxidative metabolism are linearly correlated. However, during seizures and during spreading depression, the correlation is broken, suggesting that the demand for oxidative energy exceeds that corresponding to the elevation of [K+]0. There exists a critical concentration of [K+]0 at which spreading depression inevitably erupts (12 mM for cat cerveau isole), but no such critical level could be detected for seizures. The rate of clearance of excess potassium from extracellular fluid is slower for high concentrations than for low; this rate is further slowed by the administration of phenobarbital, and possibly also of diphenylhydantoin. Changes of membrane potential of glia cells in the mammalian spinal cord can adequately be described by the Nernst equation.", "contents": "Potassium, neuroglia, and oxidative metabolism in central gray matter. Reviewed is the author's investigation of potassium in extracellular fluid of cerebral neocortex and spinal cord determined with ion-selective microelectrodes, and of oxidative metabolism monitored by fluorometric determination of intramitochondrial NADH in intact cortex. When gray matter is excited by afferent input, or by direct electrical stimulation, the logarithm of the rise of extracellular potassium concentration ([K+]0), the sustained shift of electrical potential, and the response of oxidative metabolism are linearly correlated. However, during seizures and during spreading depression, the correlation is broken, suggesting that the demand for oxidative energy exceeds that corresponding to the elevation of [K+]0. There exists a critical concentration of [K+]0 at which spreading depression inevitably erupts (12 mM for cat cerveau isole), but no such critical level could be detected for seizures. The rate of clearance of excess potassium from extracellular fluid is slower for high concentrations than for low; this rate is further slowed by the administration of phenobarbital, and possibly also of diphenylhydantoin. Changes of membrane potential of glia cells in the mammalian spinal cord can adequately be described by the Nernst equation."} {"id": "PMID:177319", "title": "Response to ACTH and dibutyryl cyclic AMP by enucleated adrenocortical tumor cells.", "content": "Y-1-L cells, a subline of the Y-1 functional murine adrenocortical tumor cell line, were enucleated with cytochalasin B and the response of these enucleated cells to ACTH and dibutyryl cyclic AMP (dbcAMP) was examined. Enucleated Y-1-L cells maintained a basal steroid output for at least 24 h and responded to either ACTH (10 mU/ml) or dbcAMP (1 mM) by a change from flat to rounded cell shape, and by increased steroidogenesis. The steroidogenic response of enucleated cells during the first 3 h after enucleation was highly significant and, though it decreased rapidly thereafter, it persisted to a limited degree for up to 12 h. On the other hand, the morphologic change could be induced even at 33 h after enucleation. The results of this study show that the nucleus is not required for the expression of the acute effects of ACTH or dbcAMP and that the cytoplasmic components necessary for cell 'rounding' and a steroidogenic response are stable for 36 h and 12 h, respectively.", "contents": "Response to ACTH and dibutyryl cyclic AMP by enucleated adrenocortical tumor cells. Y-1-L cells, a subline of the Y-1 functional murine adrenocortical tumor cell line, were enucleated with cytochalasin B and the response of these enucleated cells to ACTH and dibutyryl cyclic AMP (dbcAMP) was examined. Enucleated Y-1-L cells maintained a basal steroid output for at least 24 h and responded to either ACTH (10 mU/ml) or dbcAMP (1 mM) by a change from flat to rounded cell shape, and by increased steroidogenesis. The steroidogenic response of enucleated cells during the first 3 h after enucleation was highly significant and, though it decreased rapidly thereafter, it persisted to a limited degree for up to 12 h. On the other hand, the morphologic change could be induced even at 33 h after enucleation. The results of this study show that the nucleus is not required for the expression of the acute effects of ACTH or dbcAMP and that the cytoplasmic components necessary for cell 'rounding' and a steroidogenic response are stable for 36 h and 12 h, respectively."} {"id": "PMID:177320", "title": "Further characterization of the androgen receptor in rat testis.", "content": "Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules.", "contents": "Further characterization of the androgen receptor in rat testis. Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules."} {"id": "PMID:177321", "title": "Steroidogenesis and extracellular cAMP accumulation in adrenal tumor cell cultures.", "content": "ACTH stimulated steroidogenesis and cAMP (adenosine 3',5'-monophosphate) accumulation in an adrenocortical mouse tumor cell line (clone Y1) with Kd values which differed by more than one order of magnitude (5.2 X 10(-11) M and 7 X 10(-10) M, respectively). All of the cAMP formed in response to added ACTH appeared extracellularly in 5- or 30-min incubations. ACTH, at 5 and 10 muU/ml, stimulated steroidogenesis to 25% and 40% of maximum activity; and increased the extracellular accumulation of cAMP 1.4-fold and 2.3-fold, respectively. The effects of ACTH appeared to be via an action on intracellular ATP, specific for cAMP and dependent on an ACTH-sensitive adenylate cyclase system. These observations indicate that ACTH increases cAMP accumulation in Y1 cells at virtually all steroidogenic concentrations and suggest that cAMP is an essential component of ACTH-stimulated steroidogenesis.", "contents": "Steroidogenesis and extracellular cAMP accumulation in adrenal tumor cell cultures. ACTH stimulated steroidogenesis and cAMP (adenosine 3',5'-monophosphate) accumulation in an adrenocortical mouse tumor cell line (clone Y1) with Kd values which differed by more than one order of magnitude (5.2 X 10(-11) M and 7 X 10(-10) M, respectively). All of the cAMP formed in response to added ACTH appeared extracellularly in 5- or 30-min incubations. ACTH, at 5 and 10 muU/ml, stimulated steroidogenesis to 25% and 40% of maximum activity; and increased the extracellular accumulation of cAMP 1.4-fold and 2.3-fold, respectively. The effects of ACTH appeared to be via an action on intracellular ATP, specific for cAMP and dependent on an ACTH-sensitive adenylate cyclase system. These observations indicate that ACTH increases cAMP accumulation in Y1 cells at virtually all steroidogenic concentrations and suggest that cAMP is an essential component of ACTH-stimulated steroidogenesis."} {"id": "PMID:177322", "title": "Ontogenic development of antidiuretic hormone receptors in rat kidney: comparison of hormonal binding and adenylate cyclase activation.", "content": "The development of adenylate cyclase responsiveness to vasopressin and parathyroid hormone was studied using membrane fractions prepared from medullo-papillary and cortical portions of kidneys of 2-46-day-old rats. The development of vasopressin binding capacity was followed on the same preparations, using [3H]vasopressin. The characteristics of medullo-papillary adenylate cyclase response to vasopressin were identical in young and adult control animals as regards apparent Km values for [Lys8]vasopressin (3 X 10(-8) M), specificity towards the natural neurohypophysial peptides and the effects of Mg2+. However, the magnitude of maximal enzyme activation by vasopressin was much lower in very young than adult animals. Accordingly vasopressin responsiveness increased sharply between the 10th and 25th days but the magnitude of the maximal response only reached the adult value between the 30th and 45th days after birth. During both periods basal adenylate cyclase activity was almost independent of age. Specific vasopressin binding sites were detected on kidney medullo-papillary membranes from young animals. Vasopressin binding capacity and adenylate cyclase responsiveness to the hormone followed similar development patterns. However, the appearance of specific binding sites slightly preceded the onset of adenylate cyclase responsiveness. Basal cortical adenylate cyclase activity/mg protein was 12 times higher in 2-day-old rats than in the adult controls. It dropped with age but only fell to the adult value between the 25th and the 35th days after birth. For the youngest animals tested (2 days old), the increase in activity due to parathyroid hormone was about half the increase measured in adults, and gradually rose to about 75% of the adult response between the 2nd and 46th days after birth. Apparent Km values for parathyroid hormone were identical in young and adult animals (3.2 and 3.0 U/ml, respectively).", "contents": "Ontogenic development of antidiuretic hormone receptors in rat kidney: comparison of hormonal binding and adenylate cyclase activation. The development of adenylate cyclase responsiveness to vasopressin and parathyroid hormone was studied using membrane fractions prepared from medullo-papillary and cortical portions of kidneys of 2-46-day-old rats. The development of vasopressin binding capacity was followed on the same preparations, using [3H]vasopressin. The characteristics of medullo-papillary adenylate cyclase response to vasopressin were identical in young and adult control animals as regards apparent Km values for [Lys8]vasopressin (3 X 10(-8) M), specificity towards the natural neurohypophysial peptides and the effects of Mg2+. However, the magnitude of maximal enzyme activation by vasopressin was much lower in very young than adult animals. Accordingly vasopressin responsiveness increased sharply between the 10th and 25th days but the magnitude of the maximal response only reached the adult value between the 30th and 45th days after birth. During both periods basal adenylate cyclase activity was almost independent of age. Specific vasopressin binding sites were detected on kidney medullo-papillary membranes from young animals. Vasopressin binding capacity and adenylate cyclase responsiveness to the hormone followed similar development patterns. However, the appearance of specific binding sites slightly preceded the onset of adenylate cyclase responsiveness. Basal cortical adenylate cyclase activity/mg protein was 12 times higher in 2-day-old rats than in the adult controls. It dropped with age but only fell to the adult value between the 25th and the 35th days after birth. For the youngest animals tested (2 days old), the increase in activity due to parathyroid hormone was about half the increase measured in adults, and gradually rose to about 75% of the adult response between the 2nd and 46th days after birth. Apparent Km values for parathyroid hormone were identical in young and adult animals (3.2 and 3.0 U/ml, respectively)."} {"id": "PMID:177323", "title": "[Cachexia in mice induced by a fraction of Brucella melitensis. Modification by levamisole or by diethyldithiocarbamate of soda].", "content": "The PMF fraction of B. melitensis creates a wasting disease in newborn mice (J. infect. Dis., 1973, 127, p. 139). Administered to adult mice, PMF induces a 4 to 8 g loss of weight in 20 g mice and more markedly in males than in females. Treatment with Levamisole (LMS) suppresses this difference in response to PMF and restores normal weight in 24 days. Diethyldithiocarbamate (DDC), another immunostimulant sulfur derivate, abolishes the emaciating effect of PMF. Furthermore, DDC is an anabolizing agent which increases the weight of normal or PMF-treacted mice above the mean level of normal untreated control mice.", "contents": "[Cachexia in mice induced by a fraction of Brucella melitensis. Modification by levamisole or by diethyldithiocarbamate of soda]. The PMF fraction of B. melitensis creates a wasting disease in newborn mice (J. infect. Dis., 1973, 127, p. 139). Administered to adult mice, PMF induces a 4 to 8 g loss of weight in 20 g mice and more markedly in males than in females. Treatment with Levamisole (LMS) suppresses this difference in response to PMF and restores normal weight in 24 days. Diethyldithiocarbamate (DDC), another immunostimulant sulfur derivate, abolishes the emaciating effect of PMF. Furthermore, DDC is an anabolizing agent which increases the weight of normal or PMF-treacted mice above the mean level of normal untreated control mice."} {"id": "PMID:177324", "title": "[Epidemiology of human and animal brucellosis in western Africa. The results of six studies in the Ivory Coast, Upper Volta, and Nigeria].", "content": "Brucellosis has a two-fold importance in public health: the transmission of the disease to man by contact with animals or ingestion of raw milk is of direct importance; of indirect importance is the loss of animal protein. The authors have carried out ten epidemiological investigations in different bio-climatic zones of West Africa. More than 120 villages were evaluated. In each village, 100 persons were chosen at random and all or part of the animal population was also studied. Three tests were used for man: the melitin intradermal reaction, the sero-agglutination test of Wright and the complement fixation test. Three tests were used for the animals, the \"ring-test\" and the same serologic tests used for humans. The results indicated that brucellosis in animals exists in all regions but with varying rates. The bovine species seems to be the most contaminated. The enzooty becomes more widespread towards the South. Human brucellosis was not found to be of great importance in the regions mainly populated by farmers. Shepherds and their families in these zones, however, were found to have been infected. The highest percentage of infected humans was found in the sahelian zone (in Dori 30% of the intradermal reactions and 10% of serologies were positive for humans) in spite of a rather low infection rate among animals (6%-8% ring-tests positive among cattle). The majority of the population are shepherds and close cohabitation with animals is common. A basic dietary constituent is milk, which is often consumed raw (variable according to ethnic group), and provides the principal source of animal protein. Adults were found to have a significantly higher intradermal reaction rate in most of the regions studied. The positivity rate was higher in men than in women. In non-pastoral areas the shepherds and their families had a singificantly higher positivity rate than the general population. Ethnic differences were found. Also considered in this paper are intradermal reaction sizes, the relation between intradermal and serologic results, the modes of human transmission of the disease, and the relationship between human and animal forms of brucellosis.", "contents": "[Epidemiology of human and animal brucellosis in western Africa. The results of six studies in the Ivory Coast, Upper Volta, and Nigeria]. Brucellosis has a two-fold importance in public health: the transmission of the disease to man by contact with animals or ingestion of raw milk is of direct importance; of indirect importance is the loss of animal protein. The authors have carried out ten epidemiological investigations in different bio-climatic zones of West Africa. More than 120 villages were evaluated. In each village, 100 persons were chosen at random and all or part of the animal population was also studied. Three tests were used for man: the melitin intradermal reaction, the sero-agglutination test of Wright and the complement fixation test. Three tests were used for the animals, the \"ring-test\" and the same serologic tests used for humans. The results indicated that brucellosis in animals exists in all regions but with varying rates. The bovine species seems to be the most contaminated. The enzooty becomes more widespread towards the South. Human brucellosis was not found to be of great importance in the regions mainly populated by farmers. Shepherds and their families in these zones, however, were found to have been infected. The highest percentage of infected humans was found in the sahelian zone (in Dori 30% of the intradermal reactions and 10% of serologies were positive for humans) in spite of a rather low infection rate among animals (6%-8% ring-tests positive among cattle). The majority of the population are shepherds and close cohabitation with animals is common. A basic dietary constituent is milk, which is often consumed raw (variable according to ethnic group), and provides the principal source of animal protein. Adults were found to have a significantly higher intradermal reaction rate in most of the regions studied. The positivity rate was higher in men than in women. In non-pastoral areas the shepherds and their families had a singificantly higher positivity rate than the general population. Ethnic differences were found. Also considered in this paper are intradermal reaction sizes, the relation between intradermal and serologic results, the modes of human transmission of the disease, and the relationship between human and animal forms of brucellosis."} {"id": "PMID:177325", "title": "Changes in adenylate energy charge of the liver after an oral glucose load.", "content": "Changes in the adenine nucleotide metabolism after an oral glucose load were studied in the liver of normal and alloxan-diabetic rats. Changes in the energy charge were positively correlated with those in the blood glucose and plasma immunoreactive insulin levels. One hour after an oral glucose load when the plasma immunoreactive insulin levels increased maximally, the energy charge increased maximally from 0.846 to 0.867 (P less than 0.001). The increase in the energy charge was accompanied by a concomitant decrease in the ADP levels (P less than 0.05). The respiratory control ration, state 3 respiration per unit of cytochrome a (+a3), and DNP-induced ATPase activity per unit of cytochrome a (+a3) increased significantly. The adenylate kinase and pyruvate kinase activities in the liver remained unchanged. On the other hand, the energy charge in the liver of alloxan-diabetic rats did not increase significantly after an oral glucose load. It was suggested that an increase in the energy charge of the liver is attributable to the more rapid flux of intermediary metabolism in the enhanced ADP-phosphorylating reactions by mitochondria, owing to an elevated level of insulin available to the hepatic cells.", "contents": "Changes in adenylate energy charge of the liver after an oral glucose load. Changes in the adenine nucleotide metabolism after an oral glucose load were studied in the liver of normal and alloxan-diabetic rats. Changes in the energy charge were positively correlated with those in the blood glucose and plasma immunoreactive insulin levels. One hour after an oral glucose load when the plasma immunoreactive insulin levels increased maximally, the energy charge increased maximally from 0.846 to 0.867 (P less than 0.001). The increase in the energy charge was accompanied by a concomitant decrease in the ADP levels (P less than 0.05). The respiratory control ration, state 3 respiration per unit of cytochrome a (+a3), and DNP-induced ATPase activity per unit of cytochrome a (+a3) increased significantly. The adenylate kinase and pyruvate kinase activities in the liver remained unchanged. On the other hand, the energy charge in the liver of alloxan-diabetic rats did not increase significantly after an oral glucose load. It was suggested that an increase in the energy charge of the liver is attributable to the more rapid flux of intermediary metabolism in the enhanced ADP-phosphorylating reactions by mitochondria, owing to an elevated level of insulin available to the hepatic cells."} {"id": "PMID:177326", "title": "Re-evaluation of the role of cyclic AMP in histamine-induced gastric acid secretion.", "content": "The 600 x g particulate fraction of gastric mucosal scrapings from rats was incubated with 3H-metiamide which saturated available binding sites at a concentration of 1 muM. Scatchard plots showed a single component with a Kd value of 0.2 muM. Unlabelled cimetidine and histamine competed with 3H-metiamide binding. The 600 x g particulate fraction also contained all of the hormone and sodium fluoride sensitive adenylyl cyclase. Adenylyl cyclase activity was not altered by histamine, pentagastrin or carbachol but was increased during incubation with prostaglandin E1, secretin and epinephrine. These findings do not support the hypthesis that gastric secretion is mediated by intracellular accumulation of cyclic AMP.", "contents": "Re-evaluation of the role of cyclic AMP in histamine-induced gastric acid secretion. The 600 x g particulate fraction of gastric mucosal scrapings from rats was incubated with 3H-metiamide which saturated available binding sites at a concentration of 1 muM. Scatchard plots showed a single component with a Kd value of 0.2 muM. Unlabelled cimetidine and histamine competed with 3H-metiamide binding. The 600 x g particulate fraction also contained all of the hormone and sodium fluoride sensitive adenylyl cyclase. Adenylyl cyclase activity was not altered by histamine, pentagastrin or carbachol but was increased during incubation with prostaglandin E1, secretin and epinephrine. These findings do not support the hypthesis that gastric secretion is mediated by intracellular accumulation of cyclic AMP."} {"id": "PMID:177332", "title": "Inhibition of growth by amber suppressors in yeast.", "content": "Strains of the yeast Saccharomyces cerevisiae that contain highly efficient amber (UAG) suppressors grow poorly on nutrient medium, while normal or nearly normal growth rates are observed when these strains lose the supressors or when the suppressors are mutated to lower efficiencies. The different growth rates account for the accumulation of mutants with lowered efficiencies in cultures of strains with highly efficient amber suppressors. Genetic analyses indicate that one of the mutations with a lowered efficiency of suppression is caused by an intragenic mutation of the amber supressor. The inhibition of growth caused by excessive suppression is expected to be exacerbated when appropriate suppressors are combined together in haploid cells if two suppressors act with a greater efficiency than a single suppressor. Such retardation of growth is observed with combinations of two UAA (ochre) suppressors (Gilmore 1967) and with combinations of two UAG suppressors when the efficiencies of each of the suppressors are within a critical range. In contrast, combinations of a UAA suppressor and a UAG suppressor do not affect growth rate. Apparently while either excessive UAA or excessive UAG suppression is deleterious to yeast, a moderate level of simultaneous UAA and UAG suppression is not.", "contents": "Inhibition of growth by amber suppressors in yeast. Strains of the yeast Saccharomyces cerevisiae that contain highly efficient amber (UAG) suppressors grow poorly on nutrient medium, while normal or nearly normal growth rates are observed when these strains lose the supressors or when the suppressors are mutated to lower efficiencies. The different growth rates account for the accumulation of mutants with lowered efficiencies in cultures of strains with highly efficient amber suppressors. Genetic analyses indicate that one of the mutations with a lowered efficiency of suppression is caused by an intragenic mutation of the amber supressor. The inhibition of growth caused by excessive suppression is expected to be exacerbated when appropriate suppressors are combined together in haploid cells if two suppressors act with a greater efficiency than a single suppressor. Such retardation of growth is observed with combinations of two UAA (ochre) suppressors (Gilmore 1967) and with combinations of two UAG suppressors when the efficiencies of each of the suppressors are within a critical range. In contrast, combinations of a UAA suppressor and a UAG suppressor do not affect growth rate. Apparently while either excessive UAA or excessive UAG suppression is deleterious to yeast, a moderate level of simultaneous UAA and UAG suppression is not."} {"id": "PMID:177327", "title": "[Duodenal amebiasis].", "content": "Entamoeba histolytica was found in duodenal content obtained through fiberoptic gastroduodenoscopy in 13 patients. Clinical, radiological and endoscopic findings are analized. The possibility of an amoebic duodenitis is proposed.", "contents": "[Duodenal amebiasis]. Entamoeba histolytica was found in duodenal content obtained through fiberoptic gastroduodenoscopy in 13 patients. Clinical, radiological and endoscopic findings are analized. The possibility of an amoebic duodenitis is proposed."} {"id": "PMID:177333", "title": "Isolation and characterization of amber suppressors in yeast.", "content": "Nonsense suppressors were obtained in a haploid yeast strain containing eight nutritional mutations, that are assumed to be amber or ochre, and the cyc1-179 amber mutation that has a UAG codon corresponding to position 9 in iso-1-cytochrome c. Previous studies established that the biosynthesis and function of iso-1-cytochrome c is compatible with replacements at position 9 of amino acids having widely different structures (Stewart and Sherman 1972). UV-induced revertants, selected on media requiring the reversion of one or two of the amber nutritional markers, were presumed to contain a suppressor if there was the unselected reversion of at least one other marker. The 1088 suppressors that were isolated could be divided into 78 phenotypic classes. Only 43 suppressors of three classes caused the production of more than 50% of the normal amount of iso-1-cytochrome c in the cyc1-179 strain. Genetic analyses indicated that all of these highly efficient amber suppressors are allelic to one or another of the eight suppressors which cause the insertion of tyrosine at ochre (UAA) codons (Gilmore, Stewart and Sherman 1971). Furthermore, only tyrosine has been identified at position 9 in iso-1-cytochrome c in cyc1-179 strains suppressed with these efficient amber suppressors.", "contents": "Isolation and characterization of amber suppressors in yeast. Nonsense suppressors were obtained in a haploid yeast strain containing eight nutritional mutations, that are assumed to be amber or ochre, and the cyc1-179 amber mutation that has a UAG codon corresponding to position 9 in iso-1-cytochrome c. Previous studies established that the biosynthesis and function of iso-1-cytochrome c is compatible with replacements at position 9 of amino acids having widely different structures (Stewart and Sherman 1972). UV-induced revertants, selected on media requiring the reversion of one or two of the amber nutritional markers, were presumed to contain a suppressor if there was the unselected reversion of at least one other marker. The 1088 suppressors that were isolated could be divided into 78 phenotypic classes. Only 43 suppressors of three classes caused the production of more than 50% of the normal amount of iso-1-cytochrome c in the cyc1-179 strain. Genetic analyses indicated that all of these highly efficient amber suppressors are allelic to one or another of the eight suppressors which cause the insertion of tyrosine at ochre (UAA) codons (Gilmore, Stewart and Sherman 1971). Furthermore, only tyrosine has been identified at position 9 in iso-1-cytochrome c in cyc1-179 strains suppressed with these efficient amber suppressors."} {"id": "PMID:177334", "title": "Institutional dependence is reversible.", "content": "A project is described whereby in 12 months, 105 long-stay psychiatric patients were able to be discharged to the homes of private individuals to become members of a 'family', to whom they were not related. The task necessitated a change in attitudes of the whole hospital staff--as resistance to change was encountered in staff at all levels. A consultant psychiatrist and a social worker interviewed all the long-stay patients in the wards and with the charge nurse decided whether they could live outside the hospital given an appropriate environment. In achieving success it was calculated that the time spent on interviews, assessing placements, discussing after-care and being available to answer the many enquiries from all concerned, amounted to 1 1/2 weeks work for each patient. However, this must be considered in relation to the hours spent by professional and other hospital staff over the years spent as an inpatient.", "contents": "Institutional dependence is reversible. A project is described whereby in 12 months, 105 long-stay psychiatric patients were able to be discharged to the homes of private individuals to become members of a 'family', to whom they were not related. The task necessitated a change in attitudes of the whole hospital staff--as resistance to change was encountered in staff at all levels. A consultant psychiatrist and a social worker interviewed all the long-stay patients in the wards and with the charge nurse decided whether they could live outside the hospital given an appropriate environment. In achieving success it was calculated that the time spent on interviews, assessing placements, discussing after-care and being available to answer the many enquiries from all concerned, amounted to 1 1/2 weeks work for each patient. However, this must be considered in relation to the hours spent by professional and other hospital staff over the years spent as an inpatient."} {"id": "PMID:177336", "title": "Effects of a cold environment on energy-related enzyme activities in the postnatal rat.", "content": "Liver glucose-6-phosphatase and lipase-esterase, liver and muscle glycogen phosphorylase, and brown fat lipase-esterase activity changes were studied during the postnatal development of rats born and growing up in temperatures of +5 and 20 degrees C. Liver glucose-6-phosphatase activity was highest at the age of 4 days in both environments. In the age groups 20-67 days glucose-6-phosphatase activity was higher in animals living in a cold environment than in those reared at room temperature. At birth, glycogen phosphorylase activity was high in the liver but very low in the muscle. No difference was found between the two temperatures. The lipase-esterase activity in the liver was very low at birth, rising to adult level by the age of 30 days, while in the brown fat the activity was already high at the time of birth and clearly higher in rats born in a cold environment than in those born at room temperature. At the time of birth the relative and absolute weight of brown fat were also clearly higher in rats born at +5 degrees C than in those born +20 degrees C.", "contents": "Effects of a cold environment on energy-related enzyme activities in the postnatal rat. Liver glucose-6-phosphatase and lipase-esterase, liver and muscle glycogen phosphorylase, and brown fat lipase-esterase activity changes were studied during the postnatal development of rats born and growing up in temperatures of +5 and 20 degrees C. Liver glucose-6-phosphatase activity was highest at the age of 4 days in both environments. In the age groups 20-67 days glucose-6-phosphatase activity was higher in animals living in a cold environment than in those reared at room temperature. At birth, glycogen phosphorylase activity was high in the liver but very low in the muscle. No difference was found between the two temperatures. The lipase-esterase activity in the liver was very low at birth, rising to adult level by the age of 30 days, while in the brown fat the activity was already high at the time of birth and clearly higher in rats born in a cold environment than in those born at room temperature. At the time of birth the relative and absolute weight of brown fat were also clearly higher in rats born at +5 degrees C than in those born +20 degrees C."} {"id": "PMID:177337", "title": "The role of serum nonsuppressible insulin-like activity (NSILA) in compensatory renal growth.", "content": "The nonsuppressible insulin-like activity (NSILA) of serum is defined as the insulin-like activity measured in insulin bioassays that is not suppressed by addition of insulin antiserum. The major part of serum NSILA is attributable to a 90,000 mol wt trace protein which has been recently purified. This study was designed to evaluate the role of serum NSILA in compensatory renal growth (CRG).", "contents": "The role of serum nonsuppressible insulin-like activity (NSILA) in compensatory renal growth. The nonsuppressible insulin-like activity (NSILA) of serum is defined as the insulin-like activity measured in insulin bioassays that is not suppressed by addition of insulin antiserum. The major part of serum NSILA is attributable to a 90,000 mol wt trace protein which has been recently purified. This study was designed to evaluate the role of serum NSILA in compensatory renal growth (CRG)."} {"id": "PMID:177339", "title": "[Pre-operative embolisation of vascular tumours in the head (author's transl)].", "content": "Trans-vascular, pre-operative embolisation in order to reduce blood flow was carried out with excellent results in a patient with a naso-pharyngeal fibroma, and with relatively good results in a patient with a pterion meningioma. This technique can be carried out following the diagnostic angiogram through the same catheter; it reduces operative blood loss, improves haemostasis and the surgeon's view of the operative field. The method can be used simply and without risk in any case where the tumour blood supply is derived exclusively or predominantly from branches of external carotid artery.", "contents": "[Pre-operative embolisation of vascular tumours in the head (author's transl)]. Trans-vascular, pre-operative embolisation in order to reduce blood flow was carried out with excellent results in a patient with a naso-pharyngeal fibroma, and with relatively good results in a patient with a pterion meningioma. This technique can be carried out following the diagnostic angiogram through the same catheter; it reduces operative blood loss, improves haemostasis and the surgeon's view of the operative field. The method can be used simply and without risk in any case where the tumour blood supply is derived exclusively or predominantly from branches of external carotid artery."} {"id": "PMID:177340", "title": "[The angiographic diagnosis of trophoblastic tumours (author's transl)].", "content": "Pelvic angiograms were performed on ten patients with trophoblastic tumours. Together with a history and HCG determinations the diagnosis can be made with certainty. It is not possible to differentiate between invasive moles and chorion carcinomas. The results of chemotherapy can be clearly evaluated. A normal pelvic angiogram does not exclude a trophoblastic tumour with complete certainty, since this can be localised to other organs. It has the advantage over curettage of being able to show very small tumours, as well as tumours not situated in the uterine cavity.", "contents": "[The angiographic diagnosis of trophoblastic tumours (author's transl)]. Pelvic angiograms were performed on ten patients with trophoblastic tumours. Together with a history and HCG determinations the diagnosis can be made with certainty. It is not possible to differentiate between invasive moles and chorion carcinomas. The results of chemotherapy can be clearly evaluated. A normal pelvic angiogram does not exclude a trophoblastic tumour with complete certainty, since this can be localised to other organs. It has the advantage over curettage of being able to show very small tumours, as well as tumours not situated in the uterine cavity."} {"id": "PMID:177342", "title": "[Mental disorders caused by organic illness. The symptomatic psychoses. Conclusion].", "content": "Especially in times when psychodynamic points of view in psychiatry seem the main focus of attention, one must not forget the primary somatic basis of many psychic disturbances. If such cases are not promptly diagnosed, there is a danger that appropriate therapy will be neglected. Since every imaginable type of psychic symptomatology can at times be organically caused, the organic point of view still is of immense practical value. In addition, this latter aspect is of great theoretical importance, because it illuminates the dynamic process not only of the symptomatic psychoses but also of the so-called endogenous psychoses. After a short review of alterations of consciousness as well as the presentation of a detailled case report, psychic disturbances, which at first glance appear not to be organically determined, are described and discussed.", "contents": "[Mental disorders caused by organic illness. The symptomatic psychoses. Conclusion]. Especially in times when psychodynamic points of view in psychiatry seem the main focus of attention, one must not forget the primary somatic basis of many psychic disturbances. If such cases are not promptly diagnosed, there is a danger that appropriate therapy will be neglected. Since every imaginable type of psychic symptomatology can at times be organically caused, the organic point of view still is of immense practical value. In addition, this latter aspect is of great theoretical importance, because it illuminates the dynamic process not only of the symptomatic psychoses but also of the so-called endogenous psychoses. After a short review of alterations of consciousness as well as the presentation of a detailled case report, psychic disturbances, which at first glance appear not to be organically determined, are described and discussed."} {"id": "PMID:177345", "title": "Evaluation of the antilipolytic action of clomiphene in vitro.", "content": "Clomiphene (10(-3) - 10(-2) M) in a dose-dependent manner inhibited the lypolytic response of isolated rat epididymal adipose tissue and fat cells to epinephrine, ACTH, and dibutyryl-cyclic AMP. Furthermore, it reduced the non-hormonally stimulated activity of a crude preparation of lipase from epididymal adipose tissue. The accumulation of cyclic AMP produced by epinephrine in fat cells was not prevented by clomiphene at a concentration causing antilipolytic activity. It is concluded from these results that clomiphene unlike most other antilipolytic drugs exerts its antilipolytic effect by an inhibition of the lipase rather than by inhibition of adenylcyclase.", "contents": "Evaluation of the antilipolytic action of clomiphene in vitro. Clomiphene (10(-3) - 10(-2) M) in a dose-dependent manner inhibited the lypolytic response of isolated rat epididymal adipose tissue and fat cells to epinephrine, ACTH, and dibutyryl-cyclic AMP. Furthermore, it reduced the non-hormonally stimulated activity of a crude preparation of lipase from epididymal adipose tissue. The accumulation of cyclic AMP produced by epinephrine in fat cells was not prevented by clomiphene at a concentration causing antilipolytic activity. It is concluded from these results that clomiphene unlike most other antilipolytic drugs exerts its antilipolytic effect by an inhibition of the lipase rather than by inhibition of adenylcyclase."} {"id": "PMID:177346", "title": "Metabolic control of phosphorylase conversion in muscle. Effect of fasting and refeeding on the response of rat diaphragm glycogen phosphorylase, cyclic AMP Dependent protein kinase, and phosphorylase b kinase to adrenergic stimulation.", "content": "The influence of fasting and refeeding on the response to adrenergic stimulation of several enzymes involved in glycogen metabolism has been investigated in the isolated, intact rat diaphragm. The in vitro response of the phosphorylase system to terbutaline was found to decrease markedly following fasting. A pronounced increase in this response was seen upon refeeding. This increased responsiveness was normalized by incubation of isolated tissues with palmitate (1.5 mM). Plasma free fatty acid concentration was increased in fasted rats compared to the value found in refed animals. The effect of terbutaline on cyclic AMP concentration and protein kinase activity was not significantly influenced by fasting and refeeding while fasting decreased the effect of terbutaline upon phosphorylase b kinase. Diaphragm glycogen levels were reduced by more than 50% in rats fasted for 24 hours and were significantly increased upon refeeding compared to fed rats. The results indicate that the nutritional state can modulate the sensitivity of the interconverting system for phosphorylase. It is suggested that this modulation might depend upon fatty acid metabolism.", "contents": "Metabolic control of phosphorylase conversion in muscle. Effect of fasting and refeeding on the response of rat diaphragm glycogen phosphorylase, cyclic AMP Dependent protein kinase, and phosphorylase b kinase to adrenergic stimulation. The influence of fasting and refeeding on the response to adrenergic stimulation of several enzymes involved in glycogen metabolism has been investigated in the isolated, intact rat diaphragm. The in vitro response of the phosphorylase system to terbutaline was found to decrease markedly following fasting. A pronounced increase in this response was seen upon refeeding. This increased responsiveness was normalized by incubation of isolated tissues with palmitate (1.5 mM). Plasma free fatty acid concentration was increased in fasted rats compared to the value found in refed animals. The effect of terbutaline on cyclic AMP concentration and protein kinase activity was not significantly influenced by fasting and refeeding while fasting decreased the effect of terbutaline upon phosphorylase b kinase. Diaphragm glycogen levels were reduced by more than 50% in rats fasted for 24 hours and were significantly increased upon refeeding compared to fed rats. The results indicate that the nutritional state can modulate the sensitivity of the interconverting system for phosphorylase. It is suggested that this modulation might depend upon fatty acid metabolism."} {"id": "PMID:177347", "title": "Effect of salmon calcitonin on renal excretion of adenosine 3', 5' monophosphate in man.", "content": "Intravenous infusion of salmon calcitonin in six healthy subjects produced an increase in the plasma levels and urinary excretion of cyclic AMP. Cyclic AMP clearance diminished but remained higher than inulin clearance. Salmon calcitonin was also infused in six hypertensive patients with normal glomerular filtration rate. Arterial and renal venous plasma concentration of cyclic AMP were clearly raised. The difference between both these concentrations was not significant in the control periods but became marked during the treatment and post treatment periods demonstrating a net extraction of cyclic AMP from plasma by the kidneys. Renal extraction of cyclic AMP was lower than its urinary excretion in the control periods whereas it was clearly higher after salmon calcitonin was given. This shows that salmon calcitonin stimulates the production of cyclic AMP in extra-renal tissues and that the excess of cyclic AMP formed is catabolized by the kidneys.", "contents": "Effect of salmon calcitonin on renal excretion of adenosine 3', 5' monophosphate in man. Intravenous infusion of salmon calcitonin in six healthy subjects produced an increase in the plasma levels and urinary excretion of cyclic AMP. Cyclic AMP clearance diminished but remained higher than inulin clearance. Salmon calcitonin was also infused in six hypertensive patients with normal glomerular filtration rate. Arterial and renal venous plasma concentration of cyclic AMP were clearly raised. The difference between both these concentrations was not significant in the control periods but became marked during the treatment and post treatment periods demonstrating a net extraction of cyclic AMP from plasma by the kidneys. Renal extraction of cyclic AMP was lower than its urinary excretion in the control periods whereas it was clearly higher after salmon calcitonin was given. This shows that salmon calcitonin stimulates the production of cyclic AMP in extra-renal tissues and that the excess of cyclic AMP formed is catabolized by the kidneys."} {"id": "PMID:177348", "title": "Hyaluronidase-induced inhibition of the insulinotropic action of sulfonylureas, leucine, and glucagon in rodent isolated pancreatic islets.", "content": "Exposure of hamster pancreatic islets to hyaluronidase during isolation by means of collagenase inhibits the insulinotropic action of several chemically different sulfonylureas, leucine, and glucagon without affecting glucose-stimulated insulin secretion. This inhibition is reversible for tolbutamide and leucine but irreversible for glucagon. Hyaluronidase inhibits reversibly the insulinotropic action of tolbutamide without affecting that of glucose also in mouse and rat isolated pancreatic islets . These findings suggest the existence of functionally related pancreatic beta cell receptors for tolbutamide and leucine different from those for glucose and glucagon and illustrate the potential usefulness of hyaluronidase as an enzymatic probe applicable toward investigating the cellular mechanism of action of key insulinotropic agents.", "contents": "Hyaluronidase-induced inhibition of the insulinotropic action of sulfonylureas, leucine, and glucagon in rodent isolated pancreatic islets. Exposure of hamster pancreatic islets to hyaluronidase during isolation by means of collagenase inhibits the insulinotropic action of several chemically different sulfonylureas, leucine, and glucagon without affecting glucose-stimulated insulin secretion. This inhibition is reversible for tolbutamide and leucine but irreversible for glucagon. Hyaluronidase inhibits reversibly the insulinotropic action of tolbutamide without affecting that of glucose also in mouse and rat isolated pancreatic islets . These findings suggest the existence of functionally related pancreatic beta cell receptors for tolbutamide and leucine different from those for glucose and glucagon and illustrate the potential usefulness of hyaluronidase as an enzymatic probe applicable toward investigating the cellular mechanism of action of key insulinotropic agents."} {"id": "PMID:177351", "title": "Luteoma of pregnancy: ultrastructural features.", "content": "The ultrastructural configuration of the cells in one case of pregnancy luteoma was studied by conventional electron microscopy. The fine structure of these cells conforms closely to that of steroid hormone producing cells in other human organs, such as the adrenal cortex, testicular interstitium, and corpus luteum, particularly in terms of the presence of abundant smooth endoplasmic reticulum, dispersed Golgi apparatus, and tubular cristae in the mitochondria. Similarities were noted between the pregnancy luteoma cells and, as described by other authors, the luteinized granulosa and theca cells of the human corpus luteum and the cells of spontaneous mouse luteoma. There was a more pronounced resemblance to the granulosa cells of the corpus lutemum than to the luteinized theca cells or the mouse luteoma cells but with considerable overlap among all of them. Distinctive features, not previously described, were noted in the pregnancy luteoma cells in the form of deep cytoplasmic invaginations of the cell membrane closed by tight junctions, and peculiar pleated sinuous membranous arrays within the cytoplasm. The significance of these structures is not known. In addition mesenchymal cells of ambiguous differentiation were noted in the stroma of the tumor, suggesting that the stimulus to luteinized cell proliferation may transcend the specific ovarian mesenchymal cells and may also be exerted on the supporting stroma. On the basis of previous reports concerning the biochemical and biosynthetic patterns of sex steroid hormone production by these tumors, it is concluded that although the latter recapitulate the endocrine functions of the normal ovarian stroma rather than those of the corpus luteum, the cytoarchitecture of these tumors covers a much broader spectrum of differentiation, which may come to resemble closely although not exclusively that of luteinized granulosa cells.", "contents": "Luteoma of pregnancy: ultrastructural features. The ultrastructural configuration of the cells in one case of pregnancy luteoma was studied by conventional electron microscopy. The fine structure of these cells conforms closely to that of steroid hormone producing cells in other human organs, such as the adrenal cortex, testicular interstitium, and corpus luteum, particularly in terms of the presence of abundant smooth endoplasmic reticulum, dispersed Golgi apparatus, and tubular cristae in the mitochondria. Similarities were noted between the pregnancy luteoma cells and, as described by other authors, the luteinized granulosa and theca cells of the human corpus luteum and the cells of spontaneous mouse luteoma. There was a more pronounced resemblance to the granulosa cells of the corpus lutemum than to the luteinized theca cells or the mouse luteoma cells but with considerable overlap among all of them. Distinctive features, not previously described, were noted in the pregnancy luteoma cells in the form of deep cytoplasmic invaginations of the cell membrane closed by tight junctions, and peculiar pleated sinuous membranous arrays within the cytoplasm. The significance of these structures is not known. In addition mesenchymal cells of ambiguous differentiation were noted in the stroma of the tumor, suggesting that the stimulus to luteinized cell proliferation may transcend the specific ovarian mesenchymal cells and may also be exerted on the supporting stroma. On the basis of previous reports concerning the biochemical and biosynthetic patterns of sex steroid hormone production by these tumors, it is concluded that although the latter recapitulate the endocrine functions of the normal ovarian stroma rather than those of the corpus luteum, the cytoarchitecture of these tumors covers a much broader spectrum of differentiation, which may come to resemble closely although not exclusively that of luteinized granulosa cells."} {"id": "PMID:177352", "title": "A test for heterozygocity of 21-hydroxylase deficiency: preliminary report.", "content": "The urinary excretion of steroids was studied in 8 parents of children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency of the simple virilizing and of the salt-losing type. Eight parents of normal children served as controls. 24-hour urines before and after the injection of 40 IU of ACTH were fractionated using gas liquid chromatography on glass capillary columns. Before stimulation no excretion of pregnanetriolone was detected in heterozygous and in normal parents. Following ACTH only heterozygotes showed an excretion of pregnanetriolone in the urine. This averaged 289 mug per 24 h. Employing gas liquid chromatography on glass capillary columns heterozygous carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency may reliably be detected by their increased urinary excretion of pregnanetriolone following ACTH.", "contents": "A test for heterozygocity of 21-hydroxylase deficiency: preliminary report. The urinary excretion of steroids was studied in 8 parents of children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency of the simple virilizing and of the salt-losing type. Eight parents of normal children served as controls. 24-hour urines before and after the injection of 40 IU of ACTH were fractionated using gas liquid chromatography on glass capillary columns. Before stimulation no excretion of pregnanetriolone was detected in heterozygous and in normal parents. Following ACTH only heterozygotes showed an excretion of pregnanetriolone in the urine. This averaged 289 mug per 24 h. Employing gas liquid chromatography on glass capillary columns heterozygous carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency may reliably be detected by their increased urinary excretion of pregnanetriolone following ACTH."} {"id": "PMID:177353", "title": "Studies on the properties and tissue distribution of the isozymes of guanylate kinase in man.", "content": "The isozyme patterns of guanylate kinase were examined in fetal and adult tissues, in cultured cells and also in red cells separated by density gradient fractionation. Results from fetal and cultured cells inidcated that there are three primary isozymes a, c, and e among the seven isozymes of guanylate kinase in man. Serial secondary isozyme production in red cells in vivo showed that isozyme a produces b, c produces d, and e produces f and g. The three sets of isozymes were found to differ in the following properties: activation/inhibition by EDTA; thermostability, and molecular weights. Isoelectric points of several of the isozymes were estimated by isoelectric focusing. It was concluded that the isozymes of guanylate kinase are determined by three separate gene loci.", "contents": "Studies on the properties and tissue distribution of the isozymes of guanylate kinase in man. The isozyme patterns of guanylate kinase were examined in fetal and adult tissues, in cultured cells and also in red cells separated by density gradient fractionation. Results from fetal and cultured cells inidcated that there are three primary isozymes a, c, and e among the seven isozymes of guanylate kinase in man. Serial secondary isozyme production in red cells in vivo showed that isozyme a produces b, c produces d, and e produces f and g. The three sets of isozymes were found to differ in the following properties: activation/inhibition by EDTA; thermostability, and molecular weights. Isoelectric points of several of the isozymes were estimated by isoelectric focusing. It was concluded that the isozymes of guanylate kinase are determined by three separate gene loci."} {"id": "PMID:177354", "title": "A consideration of the role of cell surface macromolecules in the process of viral transformation.", "content": "There is extensive physiological evidence implicating the cell surface as the key organelle which mediates the cell:cell interactions which underlie both normal and neoplastic growth. This information has now been supplemented with biochemical and biophysical data which indicates that surface macromolecules, in particular the heteroglycans of transformed cells, differ from those which lie at the periphery of normal cells. In the case of cells neoplastically transformed by most tumour viruses it is clear that the small virus genome (2-5 x 10(6) daltons) cannot carry the total genetic information to accomodate these various biochemical modifications, if indeed they are encoded in separate genes (1). To examine the part played in transformation by cellular genes coding for surface heteroglycan formation, we have turned to a study of SV-3T3 cells (ts H6-15) which are temperature-sensitive for expression of the transformed cell phenotype (2). The data show that cells grown under conditions permissive and non-permissive for such expression exhibit the same pattern of formation of glycolipids, and the majority of the polypeptides of the plasma membrane. There are, however, significant differences in the synthesis of some glycopeptides. A large molecular weight, trypsin-labile glycopeptide, present at the surface of untransformed fibroblasts but barely measurable in some of their virus-transformed derivatives (3), was detected, essentially at the same level, at the surface of ts H6-15 cells grown at the permissive and non-permissive temperatures. The signficance of these observations is discussed.", "contents": "A consideration of the role of cell surface macromolecules in the process of viral transformation. There is extensive physiological evidence implicating the cell surface as the key organelle which mediates the cell:cell interactions which underlie both normal and neoplastic growth. This information has now been supplemented with biochemical and biophysical data which indicates that surface macromolecules, in particular the heteroglycans of transformed cells, differ from those which lie at the periphery of normal cells. In the case of cells neoplastically transformed by most tumour viruses it is clear that the small virus genome (2-5 x 10(6) daltons) cannot carry the total genetic information to accomodate these various biochemical modifications, if indeed they are encoded in separate genes (1). To examine the part played in transformation by cellular genes coding for surface heteroglycan formation, we have turned to a study of SV-3T3 cells (ts H6-15) which are temperature-sensitive for expression of the transformed cell phenotype (2). The data show that cells grown under conditions permissive and non-permissive for such expression exhibit the same pattern of formation of glycolipids, and the majority of the polypeptides of the plasma membrane. There are, however, significant differences in the synthesis of some glycopeptides. A large molecular weight, trypsin-labile glycopeptide, present at the surface of untransformed fibroblasts but barely measurable in some of their virus-transformed derivatives (3), was detected, essentially at the same level, at the surface of ts H6-15 cells grown at the permissive and non-permissive temperatures. The signficance of these observations is discussed."} {"id": "PMID:177356", "title": "Quantitation of estradiol receptors employing a sensitive radioimmunoassay.", "content": "A method aimed at the identification and quantitation of estradiol receptors has been developed. The test is based on competitive binding reaction between solubilized cell receptors and anti-estradiol antibodies bound to acrylamide beads, for 3H-estradiol. The technique can be employed both for estradiol radioimmunoassay and quantitation of specific receptors in tissues and appears to be a sensitive, specific and reproducible method which can be applied to the evaluation of any hormone and its receptor.", "contents": "Quantitation of estradiol receptors employing a sensitive radioimmunoassay. A method aimed at the identification and quantitation of estradiol receptors has been developed. The test is based on competitive binding reaction between solubilized cell receptors and anti-estradiol antibodies bound to acrylamide beads, for 3H-estradiol. The technique can be employed both for estradiol radioimmunoassay and quantitation of specific receptors in tissues and appears to be a sensitive, specific and reproducible method which can be applied to the evaluation of any hormone and its receptor."} {"id": "PMID:177355", "title": "The lymphocyte plasma membrane: locus of control in the immune response.", "content": "The lymphocyte plasma membrane is the locus of events which control the immune response. T and B lymphocytes, which mediate cellular and humoral immunity respectively, show distinctive plasma membrane morphologies and cell surface receptors. The dynamic state of these plasma components is emphasized by their lateral mobility in the fluid plane of the membrane, as well as variation in their structure or expression as the lymphocyte proliferates and differentiates in response to stimulation by antigen or mitogens. The best understood membrane glycoproteins are surface membrane immunoglobulins that serve as antigen receptors on B cells, and the histocompatability-beta2 microglobulin complex that has an immunoglobulin-like structure. Other less well defined surface structures showing modulation during the cell cycle may affect growth regulation of proliferating lymphocytes. Some of these are shared by fetal and neoplastic cells. Major theories of lymphocyte signaling are discussed, and the early events in lymphocyte activation are reviewed. While a complete model encompassing all these early events is not yet possible, the central issues can be usefully discussed in term of receptor-transducer-effector concepts derived by strong parallels from a knowledge of hormone-membrane interactions.", "contents": "The lymphocyte plasma membrane: locus of control in the immune response. The lymphocyte plasma membrane is the locus of events which control the immune response. T and B lymphocytes, which mediate cellular and humoral immunity respectively, show distinctive plasma membrane morphologies and cell surface receptors. The dynamic state of these plasma components is emphasized by their lateral mobility in the fluid plane of the membrane, as well as variation in their structure or expression as the lymphocyte proliferates and differentiates in response to stimulation by antigen or mitogens. The best understood membrane glycoproteins are surface membrane immunoglobulins that serve as antigen receptors on B cells, and the histocompatability-beta2 microglobulin complex that has an immunoglobulin-like structure. Other less well defined surface structures showing modulation during the cell cycle may affect growth regulation of proliferating lymphocytes. Some of these are shared by fetal and neoplastic cells. Major theories of lymphocyte signaling are discussed, and the early events in lymphocyte activation are reviewed. While a complete model encompassing all these early events is not yet possible, the central issues can be usefully discussed in term of receptor-transducer-effector concepts derived by strong parallels from a knowledge of hormone-membrane interactions."} {"id": "PMID:177361", "title": "Naturally occurring antiglobulin factors in virus neutralization: homoreactant as a factor enhancing neutralization of the infectious complex of poliovirus with the Fab' antibody fragment.", "content": "A factor present in normal rabbit sera enhanced the neutralization of the infectious complex of poliovirus with the pepsin Fab' fragment of rabbit immunoglobulin G (IgG) antibody but showed no activity for the infectious complex of the same virus with IgG antibody. The factor was associated with IgG, and its activity was inhibited by the pepsin Fab' fragment of normal rabbit IgG. The data suggest that the enhancing factor belongs to naturally occurring antiglobulin to the homologous Fab' fragment (pepsin homoreactant).", "contents": "Naturally occurring antiglobulin factors in virus neutralization: homoreactant as a factor enhancing neutralization of the infectious complex of poliovirus with the Fab' antibody fragment. A factor present in normal rabbit sera enhanced the neutralization of the infectious complex of poliovirus with the pepsin Fab' fragment of rabbit immunoglobulin G (IgG) antibody but showed no activity for the infectious complex of the same virus with IgG antibody. The factor was associated with IgG, and its activity was inhibited by the pepsin Fab' fragment of normal rabbit IgG. The data suggest that the enhancing factor belongs to naturally occurring antiglobulin to the homologous Fab' fragment (pepsin homoreactant)."} {"id": "PMID:177360", "title": "Epstein-Barr virus interactions with human lymphocyte subpopulations: virus adsorption, kinetics of expression of Epstein-Barr virus-associated nuclear antigen, and lymphocyte transformation.", "content": "In order to further understand Epstein-Barr virus (EBV)-lymphocyte interactions, we investigated a chain of events including: (i) EBV binding to human lymphocyte subpopulations; (ii) the earliest appearance of EBV-determined nuclear antigen (EBNA) in the lymphocytes after EBV infection; and (iii) establishment of continuous lymphoblastoid cell lines (LCL) by infecting with EBV different types of lymphocyte preparations from the same as well as from different donors. By using direct membrane immunofluorescence assay, we found that only a small fraction of human peripheral blood and cord blood lymphocytes (CBL), and possibly less than 31% of the T cell-depleted lymphocyte population, carry receptors for P3HR-1 strain of EBV. The number of cells carrying receptors for EBV did not vary considerably among different blood lymphocyte populations from several normal donors. EBV adsorption on lymphocyte subpopulations showed that purified thymus-dependent (T) cells and thymocytes did not adsorb EBV, in contrast to T cell-depleted lymphocyte populations and lymphoid cells from fetal liver and spleen. In CBL infected with EBV strain B95-8, EBNA was detected by anti-complement immunofluorescence as early as 18 h after infection. This indicates that EBNA is the earliest detectable EBV-determined intracellular antigen to appear after infection and before or during lymphocyte transformation by EBV. Transformation was observed only in lymphocyte cultures containing detectable thymus-independent B cells but not in cultures of purified T cells. With one exception (es-b-1), all the EBV-transformed LCL from different origins carried surface-bound immunoglobulins (a B cell marker). These included also the 10 LCL obtained by infecting cultures of adherent cells from different donors. With regard to its surface markers, ES-B-1 appeared to be an exceptional EBV genome-carrying line, and it also lacked the ability to form spontaneous rosettes with sheep erythrocytes (a T cell marker). Therefore, it is possible that ES-B-1 was derived from an atypical B cell or B cell precursor or from a so-called \"null cell\" transformed by EBV.", "contents": "Epstein-Barr virus interactions with human lymphocyte subpopulations: virus adsorption, kinetics of expression of Epstein-Barr virus-associated nuclear antigen, and lymphocyte transformation. In order to further understand Epstein-Barr virus (EBV)-lymphocyte interactions, we investigated a chain of events including: (i) EBV binding to human lymphocyte subpopulations; (ii) the earliest appearance of EBV-determined nuclear antigen (EBNA) in the lymphocytes after EBV infection; and (iii) establishment of continuous lymphoblastoid cell lines (LCL) by infecting with EBV different types of lymphocyte preparations from the same as well as from different donors. By using direct membrane immunofluorescence assay, we found that only a small fraction of human peripheral blood and cord blood lymphocytes (CBL), and possibly less than 31% of the T cell-depleted lymphocyte population, carry receptors for P3HR-1 strain of EBV. The number of cells carrying receptors for EBV did not vary considerably among different blood lymphocyte populations from several normal donors. EBV adsorption on lymphocyte subpopulations showed that purified thymus-dependent (T) cells and thymocytes did not adsorb EBV, in contrast to T cell-depleted lymphocyte populations and lymphoid cells from fetal liver and spleen. In CBL infected with EBV strain B95-8, EBNA was detected by anti-complement immunofluorescence as early as 18 h after infection. This indicates that EBNA is the earliest detectable EBV-determined intracellular antigen to appear after infection and before or during lymphocyte transformation by EBV. Transformation was observed only in lymphocyte cultures containing detectable thymus-independent B cells but not in cultures of purified T cells. With one exception (es-b-1), all the EBV-transformed LCL from different origins carried surface-bound immunoglobulins (a B cell marker). These included also the 10 LCL obtained by infecting cultures of adherent cells from different donors. With regard to its surface markers, ES-B-1 appeared to be an exceptional EBV genome-carrying line, and it also lacked the ability to form spontaneous rosettes with sheep erythrocytes (a T cell marker). Therefore, it is possible that ES-B-1 was derived from an atypical B cell or B cell precursor or from a so-called \"null cell\" transformed by EBV."} {"id": "PMID:177362", "title": "Factors influencing the production of interferon from L cells.", "content": "The production of interferon from Newcastle disease virus-infected mouse L929 cells was investigated in relation to superinduction procedures, cell density, cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels, and rate of incorporation of 14C-labeled protein hydrolysate into trichloroacetic acid-precipitable material. Densely populated cultures did not have their interferon production enhanced through \"superinduction\" using cycloheximide, actinomycin D, or the two antimetabolites in combination. These dense cultures produced more interferon per cell than less dense cultures, even though the interferon production from the latter cells could be enhanced two- to threefold by cycloheximide or combined cycloheximide and actinomycin D. Cells in densely populated cultures relative to those from sparsely populated cultures were smaller in volume, had a correspondingly reduced protein content and a lower concentration of cAMP, and were less able to concentrate 14C-labeled protein hydrolysate, although proportionally they were just as efficient in incorporating labeled precursors into trichloroacetic acid-precipitable polypeptides.", "contents": "Factors influencing the production of interferon from L cells. The production of interferon from Newcastle disease virus-infected mouse L929 cells was investigated in relation to superinduction procedures, cell density, cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels, and rate of incorporation of 14C-labeled protein hydrolysate into trichloroacetic acid-precipitable material. Densely populated cultures did not have their interferon production enhanced through \"superinduction\" using cycloheximide, actinomycin D, or the two antimetabolites in combination. These dense cultures produced more interferon per cell than less dense cultures, even though the interferon production from the latter cells could be enhanced two- to threefold by cycloheximide or combined cycloheximide and actinomycin D. Cells in densely populated cultures relative to those from sparsely populated cultures were smaller in volume, had a correspondingly reduced protein content and a lower concentration of cAMP, and were less able to concentrate 14C-labeled protein hydrolysate, although proportionally they were just as efficient in incorporating labeled precursors into trichloroacetic acid-precipitable polypeptides."} {"id": "PMID:177363", "title": "Interferon-producing capacity of germfree mice.", "content": "The general capacity of germfree mouse spleen cells to produce interferon in vitro in response to various stimuli was investigated. The interferon response of germfree mouse spleen cells in vitro, when compared with that of the conventionals, appears to be lower to some inducers. Interferon production in vitro stimulated by hemagglutinating virus of Japan (HVJ) or BHK-HVJ cells (BHK cells persistently infected with HVJ) was apparently suppressed in germfree mouse spleen cells as compared with the corresponding conventionals, whereas no difference of interferon production was observed between germfree and conventional mouse spleen cells in response to Newcastle disease virus, Escherichia coli endotoxin, poly(I:C), and phytohemagglutinin. Although monocontamination with HVJ had no enhancing effect on the interferon-producing ability of germfree mouse spleen cells in response to HVJ, conventionalization for 2 weeks greatly enhanced interferon-producing capacity.", "contents": "Interferon-producing capacity of germfree mice. The general capacity of germfree mouse spleen cells to produce interferon in vitro in response to various stimuli was investigated. The interferon response of germfree mouse spleen cells in vitro, when compared with that of the conventionals, appears to be lower to some inducers. Interferon production in vitro stimulated by hemagglutinating virus of Japan (HVJ) or BHK-HVJ cells (BHK cells persistently infected with HVJ) was apparently suppressed in germfree mouse spleen cells as compared with the corresponding conventionals, whereas no difference of interferon production was observed between germfree and conventional mouse spleen cells in response to Newcastle disease virus, Escherichia coli endotoxin, poly(I:C), and phytohemagglutinin. Although monocontamination with HVJ had no enhancing effect on the interferon-producing ability of germfree mouse spleen cells in response to HVJ, conventionalization for 2 weeks greatly enhanced interferon-producing capacity."} {"id": "PMID:177364", "title": "Evidence for a one-hit theory in the immune bactericidal reaction and demonstration of a multi-hit response for hemolysis by streptolysin O and Clostridium perfringens theta-toxin.", "content": "An analytical method was developed for estimating the number of hits necessary to lyse or kill cells in which various concentrations of the cells are treated with a constant amount of the lytic or killing agent in a constant reaction volume. The reaction may be due to a single-component agent or occur by a sequential chain of reactions due to a multi-component agent, even including side, abortive, or counter-reactions. It was clearly shown by this method that immune bactericidal reactions followed a one-hit theory. It was shown by this method that streptolysin O required four or five hits for hemolysis and Clostridium perfringens theta-toxin required two hits. These results were confirmed by both logarithmic dose-response and survival analyses. It was also shown that streptolysin O and theta-toxin can act complementarily on accumulation of the hits for hemolysis.", "contents": "Evidence for a one-hit theory in the immune bactericidal reaction and demonstration of a multi-hit response for hemolysis by streptolysin O and Clostridium perfringens theta-toxin. An analytical method was developed for estimating the number of hits necessary to lyse or kill cells in which various concentrations of the cells are treated with a constant amount of the lytic or killing agent in a constant reaction volume. The reaction may be due to a single-component agent or occur by a sequential chain of reactions due to a multi-component agent, even including side, abortive, or counter-reactions. It was clearly shown by this method that immune bactericidal reactions followed a one-hit theory. It was shown by this method that streptolysin O required four or five hits for hemolysis and Clostridium perfringens theta-toxin required two hits. These results were confirmed by both logarithmic dose-response and survival analyses. It was also shown that streptolysin O and theta-toxin can act complementarily on accumulation of the hits for hemolysis."} {"id": "PMID:177365", "title": "Antigenic characterization of intermediate adenovirus 14-11 strains associated with upper respiratory illness in a military camp.", "content": "An unusual variant of adenovirus (AV) 11 was isolated from throat and rectal swabs from six persons with upper respiratory illness in a Spanish military camp in March 1969. The same strain was serologically related to the upper respiratory illness of seven other men among 25 sample cases studied in detail. After strain purification, the virus was grouped as an AV by standard biological tests; it possessed the usual titers of group-specific hexon antigen but only low hemagglutinin titers (1:4 to 1:8) with erythrocytes from selected rhesus monkeys. The virus gave little reaction in hemagglutination inhibition (HI) tests with antisera to AV 1 through 35, but was neutralized to homologous titers by AV 11 antiserum. Reciprocally, rabbit and guinea pig antisera to the isolates possessed high HI antibody titers to prototype AV 14 and high serum neutralization (SN) antibody titers to prototype AV 11. On this basis, the variants were classified as AV 14-11 intermediates. Sequential serum specimens from the patients with and without positive cultures showed diagnostic rises in HI and SN antibody levels to the AV 14-11 intermediate and to prototype AV 11, but little response to AV 14.", "contents": "Antigenic characterization of intermediate adenovirus 14-11 strains associated with upper respiratory illness in a military camp. An unusual variant of adenovirus (AV) 11 was isolated from throat and rectal swabs from six persons with upper respiratory illness in a Spanish military camp in March 1969. The same strain was serologically related to the upper respiratory illness of seven other men among 25 sample cases studied in detail. After strain purification, the virus was grouped as an AV by standard biological tests; it possessed the usual titers of group-specific hexon antigen but only low hemagglutinin titers (1:4 to 1:8) with erythrocytes from selected rhesus monkeys. The virus gave little reaction in hemagglutination inhibition (HI) tests with antisera to AV 1 through 35, but was neutralized to homologous titers by AV 11 antiserum. Reciprocally, rabbit and guinea pig antisera to the isolates possessed high HI antibody titers to prototype AV 14 and high serum neutralization (SN) antibody titers to prototype AV 11. On this basis, the variants were classified as AV 14-11 intermediates. Sequential serum specimens from the patients with and without positive cultures showed diagnostic rises in HI and SN antibody levels to the AV 14-11 intermediate and to prototype AV 11, but little response to AV 14."} {"id": "PMID:177366", "title": "Murine leukemia: depressed response to interferon induction correlated with a serum hyporeactive factor.", "content": "Mice injected by the intraperitoneal route with either L1210 or P388 leukemic cells progressively developed a state of hyporeactivity to interferon induction that was dependent upon inducer and time of administration. A circulating factor was detected in the serum of both L1210 and P388 leukemic mice that could transfer hyporeactivity to normal murine cells in vitro. A direct relationship existed between the concentration of serum factor and development of hyporeactivity to interferon induction in vivo. Characterization of the serum hyporeactive factor from P388 or L1210 leukemic mice indicated that both were similar to a hyporeactive factor previously detected in serum from virus-infected mice. These results suggest a cause-effect relationship between the serum hyporeactive factor and development of hyporeactivity in vivo.", "contents": "Murine leukemia: depressed response to interferon induction correlated with a serum hyporeactive factor. Mice injected by the intraperitoneal route with either L1210 or P388 leukemic cells progressively developed a state of hyporeactivity to interferon induction that was dependent upon inducer and time of administration. A circulating factor was detected in the serum of both L1210 and P388 leukemic mice that could transfer hyporeactivity to normal murine cells in vitro. A direct relationship existed between the concentration of serum factor and development of hyporeactivity to interferon induction in vivo. Characterization of the serum hyporeactive factor from P388 or L1210 leukemic mice indicated that both were similar to a hyporeactive factor previously detected in serum from virus-infected mice. These results suggest a cause-effect relationship between the serum hyporeactive factor and development of hyporeactivity in vivo."} {"id": "PMID:177367", "title": "Effect of biotin deficiency on some properties of Staphylococcus aureus isolates from humans and other animals.", "content": "Staphylococcus aureus isolates from humans and other animals were grown in biotin assay medium containing 12 mug of biotin per liter and compared to isolates from the same sources grown concurrently in medium containing adequate biotin. The two cultures were tested for production of coagulase, phosphatase, and fibrinolysin enzymes and for responses to various antimicrobial agents and bacteriophages. Organisms grown in biotin-deficient medium produced less phosphatase; coagulase and fibrinolytic activity was reduced, and they were more susceptible to antimicrobial agents than were normal organisms, but phage susceptibility was not greatly affected.", "contents": "Effect of biotin deficiency on some properties of Staphylococcus aureus isolates from humans and other animals. Staphylococcus aureus isolates from humans and other animals were grown in biotin assay medium containing 12 mug of biotin per liter and compared to isolates from the same sources grown concurrently in medium containing adequate biotin. The two cultures were tested for production of coagulase, phosphatase, and fibrinolysin enzymes and for responses to various antimicrobial agents and bacteriophages. Organisms grown in biotin-deficient medium produced less phosphatase; coagulase and fibrinolytic activity was reduced, and they were more susceptible to antimicrobial agents than were normal organisms, but phage susceptibility was not greatly affected."} {"id": "PMID:177368", "title": "Fate of interferon-treated cells.", "content": "Interferon-treated cultures of Ly cells survived initial infection with high multiplicities of vesicular stomatitis (VSV) or herpes simplex virus (HSV). In the case of HSV, infectious virus and intracellular viral antigen were rapidly eliminated from the interferon-treated cultures, and the cells grew out to form apparently normal monolayers that could be cultured indefinitely. In the VSV-infected Ly cultures, virus titers remained at low levels in interferon-treated cells but after about 14 days rapidly rose and the culture was destroyed. If interferon was added to the medium on days 4 and 6 after infection, virus titers rapidly declined but again recovered and the cells were destroyed. If, however, interferon treatment was resumed 9 days after initial infection, detectable infectious VSV was eliminated from the medium. Several methods, including cocultivation and molecular hybridization, failed to demonstrate persistence of a significant portion of the VSV genome in these cultures.", "contents": "Fate of interferon-treated cells. Interferon-treated cultures of Ly cells survived initial infection with high multiplicities of vesicular stomatitis (VSV) or herpes simplex virus (HSV). In the case of HSV, infectious virus and intracellular viral antigen were rapidly eliminated from the interferon-treated cultures, and the cells grew out to form apparently normal monolayers that could be cultured indefinitely. In the VSV-infected Ly cultures, virus titers remained at low levels in interferon-treated cells but after about 14 days rapidly rose and the culture was destroyed. If interferon was added to the medium on days 4 and 6 after infection, virus titers rapidly declined but again recovered and the cells were destroyed. If, however, interferon treatment was resumed 9 days after initial infection, detectable infectious VSV was eliminated from the medium. Several methods, including cocultivation and molecular hybridization, failed to demonstrate persistence of a significant portion of the VSV genome in these cultures."} {"id": "PMID:177369", "title": "Partial characterization of the principal soluble antigens associated with the coronavirus of transmissible gastroenteritis by complement fixation and immunodiffusion.", "content": "A microtiter complement fixation (CF) test to detect transmissible gastroenteritis (TGE) viral antigen was developed, using TGE hyperimmune pig serum as an antibody source. Sera from TGE covalescent pigs did not fix complement by this test. Maximal virus and soluble antigen (SA) titers were obtained 36 to 48 h after inoculation of swine testes cells. Cell-associated virus and SA titers were higher than those in the culture fluid, which had to be concentrated 20X before use as antigen in agar immunodiffusion tests (ID). By sucrose density-gradient centrifugation, the SA had a buoyant density of 1.10 g/ml and could be separated from the virus that banded in the 1.19-g/ml region. Virus and SA from three different isolates of TGE had the same buoyant densities. Heating and proteolytic enzyme digestion established the protein nature of the SA. As assayed by CF and ID, there were stability differences between crude and purified preparations of SA. Antibody prepared in rabbits against the SA neutralized the TGE virus.", "contents": "Partial characterization of the principal soluble antigens associated with the coronavirus of transmissible gastroenteritis by complement fixation and immunodiffusion. A microtiter complement fixation (CF) test to detect transmissible gastroenteritis (TGE) viral antigen was developed, using TGE hyperimmune pig serum as an antibody source. Sera from TGE covalescent pigs did not fix complement by this test. Maximal virus and soluble antigen (SA) titers were obtained 36 to 48 h after inoculation of swine testes cells. Cell-associated virus and SA titers were higher than those in the culture fluid, which had to be concentrated 20X before use as antigen in agar immunodiffusion tests (ID). By sucrose density-gradient centrifugation, the SA had a buoyant density of 1.10 g/ml and could be separated from the virus that banded in the 1.19-g/ml region. Virus and SA from three different isolates of TGE had the same buoyant densities. Heating and proteolytic enzyme digestion established the protein nature of the SA. As assayed by CF and ID, there were stability differences between crude and purified preparations of SA. Antibody prepared in rabbits against the SA neutralized the TGE virus."} {"id": "PMID:177370", "title": "Electron microscope study of experimental enteric adenovirus infection in mice.", "content": "Using fluorescent antibody techniques (FA) and light microscopy (LM) and electron microscopy (EM), this paper describes the morphological features of the ileum in the DK1 mouse orally challenged with adenovirus K87. At the peak of infection, virus is easily identified by FA in the epithelium of the villi and crypts of the ileum. LM shows that fluorescent cells have large, bizarre, uniformly basophilic nuclei containing deoxyribonucleic acid, as indicated by histochemical tests. EM further identifies these nuclei as belonging to columnar, goblet, or Paneth cells, all epithelial cells facing the lumen with a microvillus border. The basophilic material in the nuclei consists of virus particles 75 nm in diameter arranged in crystalline arrays. When found in the cell cytoplasm, the virions do not form arrays but are scattered or form irregular aggregates, which may or may not be enclosed by single membranes. Infected columnar cells show mild cytopathic effects with no cell degeneration and necrosis, whereas the goblet and Paneth cells appear normal and maintain synthetic and secretory functions. All infected cells, however, share an abnormally accelerated extrusion rate, with columnar and goblet cells often being shed from the side rather than from the tip of the villi. The Paneth cells, which do not migrate out of the crypts, show a higher than normal rate of extrusion in the crypt lumen.", "contents": "Electron microscope study of experimental enteric adenovirus infection in mice. Using fluorescent antibody techniques (FA) and light microscopy (LM) and electron microscopy (EM), this paper describes the morphological features of the ileum in the DK1 mouse orally challenged with adenovirus K87. At the peak of infection, virus is easily identified by FA in the epithelium of the villi and crypts of the ileum. LM shows that fluorescent cells have large, bizarre, uniformly basophilic nuclei containing deoxyribonucleic acid, as indicated by histochemical tests. EM further identifies these nuclei as belonging to columnar, goblet, or Paneth cells, all epithelial cells facing the lumen with a microvillus border. The basophilic material in the nuclei consists of virus particles 75 nm in diameter arranged in crystalline arrays. When found in the cell cytoplasm, the virions do not form arrays but are scattered or form irregular aggregates, which may or may not be enclosed by single membranes. Infected columnar cells show mild cytopathic effects with no cell degeneration and necrosis, whereas the goblet and Paneth cells appear normal and maintain synthetic and secretory functions. All infected cells, however, share an abnormally accelerated extrusion rate, with columnar and goblet cells often being shed from the side rather than from the tip of the villi. The Paneth cells, which do not migrate out of the crypts, show a higher than normal rate of extrusion in the crypt lumen."} {"id": "PMID:177371", "title": "Use of cryopreserved virus-infected target cells in a lymphocytotoxicity 51Cr release microassay for cell-mediated immunity to cytomegalovirus.", "content": "A new 51Cr-release microassay is described for the measurement of cell-mediated immunity to cytomegalovirus, using cryopreserved target cells acutely infected with cytomegalovirus.", "contents": "Use of cryopreserved virus-infected target cells in a lymphocytotoxicity 51Cr release microassay for cell-mediated immunity to cytomegalovirus. A new 51Cr-release microassay is described for the measurement of cell-mediated immunity to cytomegalovirus, using cryopreserved target cells acutely infected with cytomegalovirus."} {"id": "PMID:177372", "title": "Clinical evaluation of a novel beta-lactam antibiotic: pivmecillinam (FL 1039).", "content": "Pivmecillinam, a new penicillin-like antibiotic, is a member of the amidinopenicillanic acid group. Its mode of action differs from that of the classical penicillins and it exhibits no cross-resistance with them. Fifty-two gerontopsychiatric patients, median age 81 years, with E. coli, Klebsiella, and Proteus bacteriurias were divided into three comparable groups. In a ten week open clinical trial the patients were treated with pivmecillinam, pivampicillin or the two drugs given alternately in doses reduced in stages. The bacteriuria in all groups cleared almost completely in three days. Pivmecillinam compared favourably with pivampicillin especially at the end of the reduced medication. The alternating treatment seemed to be superior to treatment with either drug administered separately. No development of resistance was observed. No toxic effect on the liver, kidney, or bone marrow was seen in any of the three groups. In the group receiving pivmecillinam alone, no ampicillin-like skin rashes occurred.", "contents": "Clinical evaluation of a novel beta-lactam antibiotic: pivmecillinam (FL 1039). Pivmecillinam, a new penicillin-like antibiotic, is a member of the amidinopenicillanic acid group. Its mode of action differs from that of the classical penicillins and it exhibits no cross-resistance with them. Fifty-two gerontopsychiatric patients, median age 81 years, with E. coli, Klebsiella, and Proteus bacteriurias were divided into three comparable groups. In a ten week open clinical trial the patients were treated with pivmecillinam, pivampicillin or the two drugs given alternately in doses reduced in stages. The bacteriuria in all groups cleared almost completely in three days. Pivmecillinam compared favourably with pivampicillin especially at the end of the reduced medication. The alternating treatment seemed to be superior to treatment with either drug administered separately. No development of resistance was observed. No toxic effect on the liver, kidney, or bone marrow was seen in any of the three groups. In the group receiving pivmecillinam alone, no ampicillin-like skin rashes occurred."} {"id": "PMID:177375", "title": "E.s.r. of free radicals in irradiated uracil-beta-D-arabinofuranoside.", "content": "Electron-spin-resonance measurements have been made on single crystals of uracil-beta-D-arabinofuranoside, which were irradiated by 4-0 MeV electrons at 77 K. At low temperatures, two radicals have been identified, one attributed to a hydrogen abstraction from 05' in the sugar moiety and the other to a radical anion located on the pyrimidine ring. The former is very unstable and seems to act as a precursor to other unidentified radical species stable at 77K. At room temperature, the main resonance is due to hydrogen addition to C5 and is probably produced by protonation of the anion. This same radical is also produced by X-irradiation at room temperature.", "contents": "E.s.r. of free radicals in irradiated uracil-beta-D-arabinofuranoside. Electron-spin-resonance measurements have been made on single crystals of uracil-beta-D-arabinofuranoside, which were irradiated by 4-0 MeV electrons at 77 K. At low temperatures, two radicals have been identified, one attributed to a hydrogen abstraction from 05' in the sugar moiety and the other to a radical anion located on the pyrimidine ring. The former is very unstable and seems to act as a precursor to other unidentified radical species stable at 77K. At room temperature, the main resonance is due to hydrogen addition to C5 and is probably produced by protonation of the anion. This same radical is also produced by X-irradiation at room temperature."} {"id": "PMID:177383", "title": "Canine herpes-induced retinal dysplasia and associated ocular anomalies.", "content": "Thirty-eight newborn Beagle puppies from eight litters of a specific pathogen-free colony maintained in isolation were inoculated with canine herpesvirus. Pups were killed between one and 30 days after inoculation. Histopathologic studies were carried out on the eyes and other tissues in conjunction with fluorescent antibody and viral isolation studies. Evidence of ocular inflammation manifested by panuveitis with the presence of intranuclear inclusion bodies was usually seen by the fourth day after infection. Eyes with severe inflammation showed peripheral anterior synechiae, cataract, and keratitis. The presence of the virus was confirmed by viral isolation from ocular tissues and fluorescent antibody studies. Developmental anomalies included retinal dysplasia with fold and tube formation of the neural retina, retardation of retinal maturation, and areas of necrosis and reorganization were seen. The retinal pigment epithelium showed initially patchy depigmentation and vacuolization and, subsequently, folding hypertrophy and duplication as well as areas of widespread atrophy and patchy loss. In some animals ectopic retina was found within cystic spaces of the optic nerve. These experiments confirm the ability of canine herpes infection in neonatal pups to produce severe ocular inflammation with subsequent retinal dysplasia and associated ocular anomalies.", "contents": "Canine herpes-induced retinal dysplasia and associated ocular anomalies. Thirty-eight newborn Beagle puppies from eight litters of a specific pathogen-free colony maintained in isolation were inoculated with canine herpesvirus. Pups were killed between one and 30 days after inoculation. Histopathologic studies were carried out on the eyes and other tissues in conjunction with fluorescent antibody and viral isolation studies. Evidence of ocular inflammation manifested by panuveitis with the presence of intranuclear inclusion bodies was usually seen by the fourth day after infection. Eyes with severe inflammation showed peripheral anterior synechiae, cataract, and keratitis. The presence of the virus was confirmed by viral isolation from ocular tissues and fluorescent antibody studies. Developmental anomalies included retinal dysplasia with fold and tube formation of the neural retina, retardation of retinal maturation, and areas of necrosis and reorganization were seen. The retinal pigment epithelium showed initially patchy depigmentation and vacuolization and, subsequently, folding hypertrophy and duplication as well as areas of widespread atrophy and patchy loss. In some animals ectopic retina was found within cystic spaces of the optic nerve. These experiments confirm the ability of canine herpes infection in neonatal pups to produce severe ocular inflammation with subsequent retinal dysplasia and associated ocular anomalies."} {"id": "PMID:177384", "title": "Light effect on the synaptic organ of the rat.", "content": "The photoreceptor synapses of albino rats show considerable pathologic changes following fluorescent light exposure. The changes in the synapses and in the lamellar membranes of the outer segments occur and progress simultaneously. Membranes proliferate in the paramitochondrial zone of the rod synaptic spherule and fine budding of the smooth endoplasmic reticulum occurs in the cone pedicle within one hour's exposure to the brightness of 500 foot candles. Proliferating paramitochondrial membranes have no cytochrome c oxidase activity and degenerate together with mitochondria by further exposure. The cone pedicles remain relatively intact in photically damaged retina.", "contents": "Light effect on the synaptic organ of the rat. The photoreceptor synapses of albino rats show considerable pathologic changes following fluorescent light exposure. The changes in the synapses and in the lamellar membranes of the outer segments occur and progress simultaneously. Membranes proliferate in the paramitochondrial zone of the rod synaptic spherule and fine budding of the smooth endoplasmic reticulum occurs in the cone pedicle within one hour's exposure to the brightness of 500 foot candles. Proliferating paramitochondrial membranes have no cytochrome c oxidase activity and degenerate together with mitochondria by further exposure. The cone pedicles remain relatively intact in photically damaged retina."} {"id": "PMID:177385", "title": "Electron microscopy of cultured mammalian lenses. II. Changes preceding and accompanying insulin-induced mitosis.", "content": "Morphological changes preceding insulin-induced mitosis in cultured rabbit lenses were characterized. The fine structure of these lenses was compared with that of lenses exposed to culture conditions in which a mitotic response failed to materialize. Lenses were cultured in: (1) medium KEI-4, i.e., a completely defined medium, which retains the central epithelium in a nonproliferating state, (2) KEI-4 plus insulin, and (3) KEI-4 plus insulin, theophylline, and dibutyryl adenosine 3':5'-cyclic monophosphate (I-DBcAMP-T). The insulin-induced mitotic response was inhibited by dibutyryl cAMP and theophylline or papaverine or 8-bromoadenosine cAMP. At one hour, lenses cultured in KEI-4 alone or in KEI-4-I-DBcAMP-T showed a moderate increase in free ribosomes relative to zero hour controls. In contrast, lenses exposed to KEI-4-insulin exhibited a pronounced increase in the number of free ribosomes and had prominent nucleoli. An increase in the degree of folding of the cell membrane was detected in all lenses at three hours but was decidedly more prominent in lenses cultured in KEI-4-insulin. At seven hours, lenses exposed to KEI-4-insulin showed an increase in the size and apparent number of mitochondria. At all intervals, ribosomes were more numerous in lenses cultured in KEI-4-insulin. Lenses cultured in medium KEI-4 alone for 24 and 52 hours displayed a morphology ostensibly similar to that of zero hour controls. At 52 hours the epithelial cells of lenses exposed to insulin, DBcAMP and theophylline were multilayered and markedly elongated. The increase in ribosomes (one hour), changes in the cell membrane (three hours), and the heightened mitochondria profile all precede the initiation of DNA synthesis and mitosis which commenced at 24 and 40 hours, respectively.", "contents": "Electron microscopy of cultured mammalian lenses. II. Changes preceding and accompanying insulin-induced mitosis. Morphological changes preceding insulin-induced mitosis in cultured rabbit lenses were characterized. The fine structure of these lenses was compared with that of lenses exposed to culture conditions in which a mitotic response failed to materialize. Lenses were cultured in: (1) medium KEI-4, i.e., a completely defined medium, which retains the central epithelium in a nonproliferating state, (2) KEI-4 plus insulin, and (3) KEI-4 plus insulin, theophylline, and dibutyryl adenosine 3':5'-cyclic monophosphate (I-DBcAMP-T). The insulin-induced mitotic response was inhibited by dibutyryl cAMP and theophylline or papaverine or 8-bromoadenosine cAMP. At one hour, lenses cultured in KEI-4 alone or in KEI-4-I-DBcAMP-T showed a moderate increase in free ribosomes relative to zero hour controls. In contrast, lenses exposed to KEI-4-insulin exhibited a pronounced increase in the number of free ribosomes and had prominent nucleoli. An increase in the degree of folding of the cell membrane was detected in all lenses at three hours but was decidedly more prominent in lenses cultured in KEI-4-insulin. At seven hours, lenses exposed to KEI-4-insulin showed an increase in the size and apparent number of mitochondria. At all intervals, ribosomes were more numerous in lenses cultured in KEI-4-insulin. Lenses cultured in medium KEI-4 alone for 24 and 52 hours displayed a morphology ostensibly similar to that of zero hour controls. At 52 hours the epithelial cells of lenses exposed to insulin, DBcAMP and theophylline were multilayered and markedly elongated. The increase in ribosomes (one hour), changes in the cell membrane (three hours), and the heightened mitochondria profile all precede the initiation of DNA synthesis and mitosis which commenced at 24 and 40 hours, respectively."} {"id": "PMID:177386", "title": "Biohazard potential: recovery of infectious virus from the liquid nitrogen of a virus repository.", "content": "Flame-sealed glass ampules containing vesicular stomatitis (VSV) were submerged in a liquid nitrogen (LN2) refrigerator for storage. Onseveral occasions cracked or shattered ampules were discovered upon removal from the refrigerator. Subsequently, VSV was recovered from the LN2 of the virus repository indicating a source of potential danger to those employing glass ampules submerged in LN2 for preservation of pathogenic organisms.", "contents": "Biohazard potential: recovery of infectious virus from the liquid nitrogen of a virus repository. Flame-sealed glass ampules containing vesicular stomatitis (VSV) were submerged in a liquid nitrogen (LN2) refrigerator for storage. Onseveral occasions cracked or shattered ampules were discovered upon removal from the refrigerator. Subsequently, VSV was recovered from the LN2 of the virus repository indicating a source of potential danger to those employing glass ampules submerged in LN2 for preservation of pathogenic organisms."} {"id": "PMID:177387", "title": "Endocrine changes in sepsis.", "content": "The hormonal changes associated with sepsis appear to be important compensatory responses directed toward (1) increasing the availability of fuel (glucose, fatty acids, and amino acids) for the greatly accelerated needs of the cellular metabolic machinery and (2) maintaining an adequate blood volume, blood pressure, and tissue perfusion. Unrecognized or inadequately treated sepsis with subsequent prolonged trophic hormone stimulation depletes the patient of fuels necessary for the maintenance of the increased metabolic demands. This leads to eventual deleterious effects with muscle wasting, increased susceptibility to infection, and impaired wound healing. Manipulation of some of the hormones in sepsis, particularly insulin, glucagon, and growth hormone, with an adequate caloric intake to promote a more favorable anabolic response, holds exciting promise.", "contents": "Endocrine changes in sepsis. The hormonal changes associated with sepsis appear to be important compensatory responses directed toward (1) increasing the availability of fuel (glucose, fatty acids, and amino acids) for the greatly accelerated needs of the cellular metabolic machinery and (2) maintaining an adequate blood volume, blood pressure, and tissue perfusion. Unrecognized or inadequately treated sepsis with subsequent prolonged trophic hormone stimulation depletes the patient of fuels necessary for the maintenance of the increased metabolic demands. This leads to eventual deleterious effects with muscle wasting, increased susceptibility to infection, and impaired wound healing. Manipulation of some of the hormones in sepsis, particularly insulin, glucagon, and growth hormone, with an adequate caloric intake to promote a more favorable anabolic response, holds exciting promise."} {"id": "PMID:177393", "title": "Lipid-laden aqueous humor associated with anterior uveitis and concurrent hyperlipemia in two dogs.", "content": "Two dogs with cloudy aqueous humor due to accumulation of lipid and lipoprotein had concurrent hyperlipemia and anterior uveitis. In 1 dog, serum and aqueous humor had similar lipoprotein electrophoretic patterns, and in the other dog, the patterns were different. The therapeutic approach included symptomatic treatment of the uveitis and reduction of dietary fat intake. Clearing of fat from aqueous humor followed control of the uveitis.", "contents": "Lipid-laden aqueous humor associated with anterior uveitis and concurrent hyperlipemia in two dogs. Two dogs with cloudy aqueous humor due to accumulation of lipid and lipoprotein had concurrent hyperlipemia and anterior uveitis. In 1 dog, serum and aqueous humor had similar lipoprotein electrophoretic patterns, and in the other dog, the patterns were different. The therapeutic approach included symptomatic treatment of the uveitis and reduction of dietary fat intake. Clearing of fat from aqueous humor followed control of the uveitis."} {"id": "PMID:177396", "title": "Control of inositol biosynthesis in Saccharomyces cerevisiae; inositol-phosphate synthetase mutants.", "content": "Inositol-requiring mutants of Saacharomyces cerevisiae were tested in cell extracts for the ability to convert glucose-6-phosphate to inositol-phosphate (IP synthetase) and inositol (IP phosphatase). Mutants representing any one of 10 unlinked loci conferring the inositol requirement were unable to synthesize either compound in an assay with glucose-6-phosphate as the substrate. These results indicate that the mutants lack IP synthetase activity and that at least 10 genes control the conversion of glucose-6-phosphate to inositol-phosphate. In addition, a mutation known to be unlinked with the ino1 locus interacts with a leaky ino1 allele and may play a role in the regulation of IP synthetase. This mutation causes a 47% reduction in wild-type IP synthetase activity and, when combined in a haploid strain with the leaky ino1 allele, it reduced IP synthetase activity to a level below that which is growth supporting. Wild-type and IP synthetase-deficient strains were tested for reduced nicotinamide adenine dinucleotide (NADH) accumulation, since NAD+ is required in the conversion of glucose-6-phosphate to inositol. No detectable accumulation of NADH was observed in the wild-type strain, presumably because the NADH generated is rapidly oxidized during subsequent partial reactions of IP synthetase. Mutants representing three different loci accumulate NADH and may, therefore, lack the NADH-mediated reductase activity of IP synthetase. Other mutants tested fail to accumulate NADH and may, therefore, lack the NAD+-mediated oxidase activity of IP synthetase. Phospholipid synthesis was studied by 32P pulse labeling in one mutant under conditions of inositol supplementation and starvation. Starved cells incorporate 32P into phospholipids normally for 2 h, followed by a period in which the rate of phosphatidylinositol synthesis decreases and the rate of phosphatidylcholine synthesis increases. After 5 to 6 h starvation, all cellular phospholipid synthesis ceases.", "contents": "Control of inositol biosynthesis in Saccharomyces cerevisiae; inositol-phosphate synthetase mutants. Inositol-requiring mutants of Saacharomyces cerevisiae were tested in cell extracts for the ability to convert glucose-6-phosphate to inositol-phosphate (IP synthetase) and inositol (IP phosphatase). Mutants representing any one of 10 unlinked loci conferring the inositol requirement were unable to synthesize either compound in an assay with glucose-6-phosphate as the substrate. These results indicate that the mutants lack IP synthetase activity and that at least 10 genes control the conversion of glucose-6-phosphate to inositol-phosphate. In addition, a mutation known to be unlinked with the ino1 locus interacts with a leaky ino1 allele and may play a role in the regulation of IP synthetase. This mutation causes a 47% reduction in wild-type IP synthetase activity and, when combined in a haploid strain with the leaky ino1 allele, it reduced IP synthetase activity to a level below that which is growth supporting. Wild-type and IP synthetase-deficient strains were tested for reduced nicotinamide adenine dinucleotide (NADH) accumulation, since NAD+ is required in the conversion of glucose-6-phosphate to inositol. No detectable accumulation of NADH was observed in the wild-type strain, presumably because the NADH generated is rapidly oxidized during subsequent partial reactions of IP synthetase. Mutants representing three different loci accumulate NADH and may, therefore, lack the NADH-mediated reductase activity of IP synthetase. Other mutants tested fail to accumulate NADH and may, therefore, lack the NAD+-mediated oxidase activity of IP synthetase. Phospholipid synthesis was studied by 32P pulse labeling in one mutant under conditions of inositol supplementation and starvation. Starved cells incorporate 32P into phospholipids normally for 2 h, followed by a period in which the rate of phosphatidylinositol synthesis decreases and the rate of phosphatidylcholine synthesis increases. After 5 to 6 h starvation, all cellular phospholipid synthesis ceases."} {"id": "PMID:177397", "title": "Genetics and complementation of Haemophilus influenzae mutants deficient in adenosine 5'-triphosphate-dependent nuclease.", "content": "Eight different mutations in Haemophilus influenzae leading to deficiency in adenosine 5'-triphosphate (ATP)-dependent nuclease have been investigated in strains in which the mutations of the originally mutagenized strains have been transferred into the wild type. Sensitivity to mitomycin C and deoxycholate and complementation between extracts and deoxyribonucleic acid (DNA)-dependent ATPase activity have been measured. Genetic crosses have provided information on the relative position of the mutations on the genome. There are three complementation groups, corresponding to three genetic groups. The strains most sensitive to mitomycin and deoxycholate, derived from mutants originally selected on the basis of sensitivity to mitomycin C or methyl methanesulfonate, are in one group. Apparently all these sensitive strains lack DNA-dependent ATPase activity, as does a strain intermediate in sensitivity to deoxycholate, which is the sole representative of another group. There are four strains that are relatively resistant to deoxycholate and mitomycin C, and all of these contain the ATPase activity. Three of these are in the same genetic and complementation group, whereas the other incongruously belongs in the same group as the sensitive strains. It is postulated that there are three cistrons in H. influenzae that code for the three known subunits of the ATP-dependent nuclease.", "contents": "Genetics and complementation of Haemophilus influenzae mutants deficient in adenosine 5'-triphosphate-dependent nuclease. Eight different mutations in Haemophilus influenzae leading to deficiency in adenosine 5'-triphosphate (ATP)-dependent nuclease have been investigated in strains in which the mutations of the originally mutagenized strains have been transferred into the wild type. Sensitivity to mitomycin C and deoxycholate and complementation between extracts and deoxyribonucleic acid (DNA)-dependent ATPase activity have been measured. Genetic crosses have provided information on the relative position of the mutations on the genome. There are three complementation groups, corresponding to three genetic groups. The strains most sensitive to mitomycin and deoxycholate, derived from mutants originally selected on the basis of sensitivity to mitomycin C or methyl methanesulfonate, are in one group. Apparently all these sensitive strains lack DNA-dependent ATPase activity, as does a strain intermediate in sensitivity to deoxycholate, which is the sole representative of another group. There are four strains that are relatively resistant to deoxycholate and mitomycin C, and all of these contain the ATPase activity. Three of these are in the same genetic and complementation group, whereas the other incongruously belongs in the same group as the sensitive strains. It is postulated that there are three cistrons in H. influenzae that code for the three known subunits of the ATP-dependent nuclease."} {"id": "PMID:177398", "title": "Control of Neurospora crassa morphology by cyclic adenosine 3', 5'-monophosphate and dibutyryl cyclic adenosine 3', 5'-monophosphate.", "content": "The role of cyclic adenosine 3', 5'-monophosphate (cyclic AMP) in the control of the Neurospora asexual life cycle was studied. Endogenous cyclic AMP levels were 10 to 20 times higher in strains having the wild-type cr-1 allele than in those carrying the mutated allele. In a wild-type strain these levels remained constant throughtout the entire growth period in shaken liquid cultures, except during a short period at the beginning of the stationary growth phase. In this period a marked increase in the cyclic nucleotide level was observed. The culture of cr-1 mutant strains in the presence of cyclic AMP or its dibutyryl derivative restores some morphological properties characteristic of wild-type strains. Specifically these cyclic nucleotides stimulated the rate of mycelial elongation, as well as the differentiation of aerial hyphae.", "contents": "Control of Neurospora crassa morphology by cyclic adenosine 3', 5'-monophosphate and dibutyryl cyclic adenosine 3', 5'-monophosphate. The role of cyclic adenosine 3', 5'-monophosphate (cyclic AMP) in the control of the Neurospora asexual life cycle was studied. Endogenous cyclic AMP levels were 10 to 20 times higher in strains having the wild-type cr-1 allele than in those carrying the mutated allele. In a wild-type strain these levels remained constant throughtout the entire growth period in shaken liquid cultures, except during a short period at the beginning of the stationary growth phase. In this period a marked increase in the cyclic nucleotide level was observed. The culture of cr-1 mutant strains in the presence of cyclic AMP or its dibutyryl derivative restores some morphological properties characteristic of wild-type strains. Specifically these cyclic nucleotides stimulated the rate of mycelial elongation, as well as the differentiation of aerial hyphae."} {"id": "PMID:177399", "title": "Hypersensitivity to catabolite repression in the L-arabinose operon of Escherichia coli B/r is trans acting.", "content": "Mutations causing hypersensitivity to catabolite repression have been assigned to gene araC (activator protein) by complementation analysis. The araO (operator region) is non-essential for catabolite repression.", "contents": "Hypersensitivity to catabolite repression in the L-arabinose operon of Escherichia coli B/r is trans acting. Mutations causing hypersensitivity to catabolite repression have been assigned to gene araC (activator protein) by complementation analysis. The araO (operator region) is non-essential for catabolite repression."} {"id": "PMID:177400", "title": "Formation in the dark, of virus-induced deoxyribonuclease activity in Anacystis nidulans, an obligate photoautotroph.", "content": "In Anacystis nidulans, upon infection with cyanophage AS-1, after a lag period of 1 h the level of deoxyribonuclease (DNase) activity increaded rapidly up to 15- to 20-fold in 4 to 5 h in the light. In contrast, the ribonuclease and phosphomonoesterase activities increased significantly only 4 to 5 h after infection, i.e. as late as 1 h prior to lysis. In complete darkness, the nuclease levels remained unaltered. However, when the infected cells were exposed to light for 1 or 2 h after infection, the DNase level increased essentially to the same extent in the dark as in continuous light, although the complete replication cycle of the virus was impaired in the dark and cells lysed only in the continuously illuminated cultures. Inhibition of photosystem II with 3-(3,4-dichlorophenyl)-1-dimethylurea during the early illumination period strongly decreased the subsequent, infection-dependent increase in DNase activity in the dark. The virus-induced increase in DNase activity was also inhibited by chloramphenicol. The data suggest that, in spite of the obligate photoautotrophic nature of A. nidulans, dark metabolism is able to support fully the formation of some specific proteins if the triggering of their synthesis takes place in light.", "contents": "Formation in the dark, of virus-induced deoxyribonuclease activity in Anacystis nidulans, an obligate photoautotroph. In Anacystis nidulans, upon infection with cyanophage AS-1, after a lag period of 1 h the level of deoxyribonuclease (DNase) activity increaded rapidly up to 15- to 20-fold in 4 to 5 h in the light. In contrast, the ribonuclease and phosphomonoesterase activities increased significantly only 4 to 5 h after infection, i.e. as late as 1 h prior to lysis. In complete darkness, the nuclease levels remained unaltered. However, when the infected cells were exposed to light for 1 or 2 h after infection, the DNase level increased essentially to the same extent in the dark as in continuous light, although the complete replication cycle of the virus was impaired in the dark and cells lysed only in the continuously illuminated cultures. Inhibition of photosystem II with 3-(3,4-dichlorophenyl)-1-dimethylurea during the early illumination period strongly decreased the subsequent, infection-dependent increase in DNase activity in the dark. The virus-induced increase in DNase activity was also inhibited by chloramphenicol. The data suggest that, in spite of the obligate photoautotrophic nature of A. nidulans, dark metabolism is able to support fully the formation of some specific proteins if the triggering of their synthesis takes place in light."} {"id": "PMID:177401", "title": "Growth rate modulation of four aminoacyl-transfer ribonucleic acid synthetases in enteric bacteria.", "content": "The specific activities of arginyl- glutamyl- seryl-, and valyl-transfer ribonucleic acid (tRNA) synthetases were measured in the wild-type and mutant strains of Salmonella typhimurium LT2 and Escherichia coli B/r. In media restricted only by carbon and energy source availability, the specific activities of all four enzymes were proportional to the growth rate, with the exception of seryl-tRNA synthetase in S. typhimurium, which remained essentially constant. Structural gene densities were calculated for these four enzymes and were found not to account for the variation of specific activity with growth rate.", "contents": "Growth rate modulation of four aminoacyl-transfer ribonucleic acid synthetases in enteric bacteria. The specific activities of arginyl- glutamyl- seryl-, and valyl-transfer ribonucleic acid (tRNA) synthetases were measured in the wild-type and mutant strains of Salmonella typhimurium LT2 and Escherichia coli B/r. In media restricted only by carbon and energy source availability, the specific activities of all four enzymes were proportional to the growth rate, with the exception of seryl-tRNA synthetase in S. typhimurium, which remained essentially constant. Structural gene densities were calculated for these four enzymes and were found not to account for the variation of specific activity with growth rate."} {"id": "PMID:177402", "title": "Methyl methane sulfonate-sensitive mutant of Escherichia coli deficient in an endonuclease specific for apurinic sites in deoxyribonucleic acid.", "content": "A methyl methane sulfonate (MMS)-sensitive mutant of Escherichia coli AB 1157 was obtained by N-methyl-N'-nitro-N-nitrosoguanidine treatment. The mutant strain, AB 3027, is defective both in endonuclease activity for apurinic sites in deoxyribonucleic acid (DNA) and in DNA polymerase I, as shown by direct enzyme assays. Derivative strains, which retained the deficiency in endonuclease activity for apurinic sties (approximately 10% of the wild-type enzyme level) but had normal DNA polymerase I activity, were obtained by P1-mediated transduction (strain NH5016) or by selection of revertants to decreased MMS sensitivity. These endonuclease-deficient strains are more MMS-sensitive than wild-type strains. Revertants of these deficients strains to normal MMS resistance were isolated. They had increased levels of the endonuclease activity but did not attain wild-type levels. The data suggest that endonuclease for apurinic sites is active in repair of lesions introduced in DNA as a consequence of MMS treatment. Two different endonucleases that specifically attack DNA containing apurinic sites arepresented in E coli K-12. A heat-labile activity, sensitive to inhibition by ethylenediaminetetraacetate, accounts for 90% of the total endonuclease activity for apurinic sties in crude cell extracts. The residual 10% is due to a more heat-resistant activity, refractory to ethylenediaminetetraacetate inhibition. The AB3027 and NH5016 strains have normal amounts of the latter endonuclease but no or very little of the former activity.", "contents": "Methyl methane sulfonate-sensitive mutant of Escherichia coli deficient in an endonuclease specific for apurinic sites in deoxyribonucleic acid. A methyl methane sulfonate (MMS)-sensitive mutant of Escherichia coli AB 1157 was obtained by N-methyl-N'-nitro-N-nitrosoguanidine treatment. The mutant strain, AB 3027, is defective both in endonuclease activity for apurinic sites in deoxyribonucleic acid (DNA) and in DNA polymerase I, as shown by direct enzyme assays. Derivative strains, which retained the deficiency in endonuclease activity for apurinic sties (approximately 10% of the wild-type enzyme level) but had normal DNA polymerase I activity, were obtained by P1-mediated transduction (strain NH5016) or by selection of revertants to decreased MMS sensitivity. These endonuclease-deficient strains are more MMS-sensitive than wild-type strains. Revertants of these deficients strains to normal MMS resistance were isolated. They had increased levels of the endonuclease activity but did not attain wild-type levels. The data suggest that endonuclease for apurinic sites is active in repair of lesions introduced in DNA as a consequence of MMS treatment. Two different endonucleases that specifically attack DNA containing apurinic sites arepresented in E coli K-12. A heat-labile activity, sensitive to inhibition by ethylenediaminetetraacetate, accounts for 90% of the total endonuclease activity for apurinic sties in crude cell extracts. The residual 10% is due to a more heat-resistant activity, refractory to ethylenediaminetetraacetate inhibition. The AB3027 and NH5016 strains have normal amounts of the latter endonuclease but no or very little of the former activity."} {"id": "PMID:177403", "title": "Product analysis of bisulfite reductase activity isolated from Desulfovibrio vulgaris.", "content": "Bisulfite reductase was purified from extracts of Desulfovibrio vulgaris. By colorimetric analyses trithionate was found to be the major product, being formed in quantities 5 to 10 times more than two other detectable products, thiosulfate and sulfide. When [35S]bisulfite was used as the substrate, all three products were radioactively labeled. Degradation of [35S]trithionate showed that all of its sulfur atoms were equally labeled. In contrast, [35S]thiosulfate contained virtually all of the radioactivity in the sulfonate atom while the sulfane atom was unlabeled. These results, in conjunction with the funding that the sulfide was radioactive, led to the conclusion that bisulfite reductase reduced bisulfite to trithionate as the major product and sulfide as the minor product; the reason for the unusual labeling pattern found in the thiosulfate molecule was not apparent at this time. When bisulfite reductase was incubated with [35S]bisulfite in the presence of another protein fraction, FII, the thiosulfate formed from this reaction contained both sulfur atoms having equal radioactivity. This discovery, plus the fact that trithionate was not reduced to thiosulfate under identical conditions, led to the speculation that bisulfite could be reduced to thiosulfate by another pathway not involving trithionate.", "contents": "Product analysis of bisulfite reductase activity isolated from Desulfovibrio vulgaris. Bisulfite reductase was purified from extracts of Desulfovibrio vulgaris. By colorimetric analyses trithionate was found to be the major product, being formed in quantities 5 to 10 times more than two other detectable products, thiosulfate and sulfide. When [35S]bisulfite was used as the substrate, all three products were radioactively labeled. Degradation of [35S]trithionate showed that all of its sulfur atoms were equally labeled. In contrast, [35S]thiosulfate contained virtually all of the radioactivity in the sulfonate atom while the sulfane atom was unlabeled. These results, in conjunction with the funding that the sulfide was radioactive, led to the conclusion that bisulfite reductase reduced bisulfite to trithionate as the major product and sulfide as the minor product; the reason for the unusual labeling pattern found in the thiosulfate molecule was not apparent at this time. When bisulfite reductase was incubated with [35S]bisulfite in the presence of another protein fraction, FII, the thiosulfate formed from this reaction contained both sulfur atoms having equal radioactivity. This discovery, plus the fact that trithionate was not reduced to thiosulfate under identical conditions, led to the speculation that bisulfite could be reduced to thiosulfate by another pathway not involving trithionate."} {"id": "PMID:177404", "title": "Role of deoxyribonucleic acid polymerases and deoxyribonucleic acid ligase in x-ray-induced repair synthesis in toluene-treated Escherichia coli K-12.", "content": "Toluene-treated Escherichia coli mutants have been used to study the roles of deoxyribonucleic acid (DNA) polymerases I, II, and III, and of DNA ligase in repair synthesis and strand rejoining following X-irradiation. In cells possessing all three DNA polymerases, both a greater amount of repair synthesis (\"exaggerated\" repair synthesis) and failure of ligation are observed when DNA ligase activity is inhibited. In a mutant lacking the polymerizing activity of DNA polymerase I, exaggerated repair synthesis is not observed, and strand rejoining does not occur even if DNA ligase is fully activated. In a mutant possessing the polymerizing activity of DNA polymerase I but lacking its 5'leads to 3' exonuclease activity, exaggerated repair synthesis is minimal. After irradiation, DNA polymerases II and III are capable of carrying out an adenosine 5'-triphosphate-dependent repair synthesis,but rejoining of strand breaks does not occur and exaggerated synthesis is not seen whether DNA ligase is active or not. These results suggest that DNA polymerase I and DNA ligase act together to limit repair synthesis after X irradiation and that both are necessary in toluene-treated cells for strand rejoining. DNA polymerases II and III apparently cannot complete chain elongation and gap filling, and therefore repair carried out by these enzymes does not respond to ligase action.", "contents": "Role of deoxyribonucleic acid polymerases and deoxyribonucleic acid ligase in x-ray-induced repair synthesis in toluene-treated Escherichia coli K-12. Toluene-treated Escherichia coli mutants have been used to study the roles of deoxyribonucleic acid (DNA) polymerases I, II, and III, and of DNA ligase in repair synthesis and strand rejoining following X-irradiation. In cells possessing all three DNA polymerases, both a greater amount of repair synthesis (\"exaggerated\" repair synthesis) and failure of ligation are observed when DNA ligase activity is inhibited. In a mutant lacking the polymerizing activity of DNA polymerase I, exaggerated repair synthesis is not observed, and strand rejoining does not occur even if DNA ligase is fully activated. In a mutant possessing the polymerizing activity of DNA polymerase I but lacking its 5'leads to 3' exonuclease activity, exaggerated repair synthesis is minimal. After irradiation, DNA polymerases II and III are capable of carrying out an adenosine 5'-triphosphate-dependent repair synthesis,but rejoining of strand breaks does not occur and exaggerated synthesis is not seen whether DNA ligase is active or not. These results suggest that DNA polymerase I and DNA ligase act together to limit repair synthesis after X irradiation and that both are necessary in toluene-treated cells for strand rejoining. DNA polymerases II and III apparently cannot complete chain elongation and gap filling, and therefore repair carried out by these enzymes does not respond to ligase action."} {"id": "PMID:177405", "title": "Plasmid-determined alcohol dehydrogenase activity in alkane-utilizing strains of Pseudomonas putida.", "content": "We have identified an alcohol dehydrogenase activity in Pseudomonas putida strains carrying the CAM-OCT degradative plasmid that were grown on octane. The activity is nicotinamide adenine dinucleotide independent, sediments at 48,000 x g, and shows 20-fold greater activity with octanol rather than butanol as substrate. The enzyme is inducible by unoxidized alkane and is present only in strains that have the OCT plasmid genes for alkane degradation with a wild-type alcO locus. No analogous chromosomal dehydrogenase could be detected. Wild-type and actanol-negative mutants (alcA-) without plasmids both contain a constitutive nicotinamide adenine dinucleotide-linked soluble alcohol dehydrogenase activity. This means that alcA- mutants are cryptic for octanol oxidation and suggests that the particulate plasmid-coded alcohol dehydrogenase activity is active on surface- or membrane-bound substrate.", "contents": "Plasmid-determined alcohol dehydrogenase activity in alkane-utilizing strains of Pseudomonas putida. We have identified an alcohol dehydrogenase activity in Pseudomonas putida strains carrying the CAM-OCT degradative plasmid that were grown on octane. The activity is nicotinamide adenine dinucleotide independent, sediments at 48,000 x g, and shows 20-fold greater activity with octanol rather than butanol as substrate. The enzyme is inducible by unoxidized alkane and is present only in strains that have the OCT plasmid genes for alkane degradation with a wild-type alcO locus. No analogous chromosomal dehydrogenase could be detected. Wild-type and actanol-negative mutants (alcA-) without plasmids both contain a constitutive nicotinamide adenine dinucleotide-linked soluble alcohol dehydrogenase activity. This means that alcA- mutants are cryptic for octanol oxidation and suggests that the particulate plasmid-coded alcohol dehydrogenase activity is active on surface- or membrane-bound substrate."} {"id": "PMID:177406", "title": "Lack of glucose phosphotransferase function in phosphofructokinase mutants of Escherichia coli.", "content": "Phosphofructokinase (pfkA) mutants of Escherichia coli are impaired in growth on all carbon sources entering glycolysis at or above the level of fructose 6-phosphate (nonpermissive carbon sources), but growth is particularly slow on sugars, such as glucose, which are normally transported and phosphorylated by the phosphoenolpyruvate, (PEP)-dependent phosphotransferase system (PTS).", "contents": "Lack of glucose phosphotransferase function in phosphofructokinase mutants of Escherichia coli. Phosphofructokinase (pfkA) mutants of Escherichia coli are impaired in growth on all carbon sources entering glycolysis at or above the level of fructose 6-phosphate (nonpermissive carbon sources), but growth is particularly slow on sugars, such as glucose, which are normally transported and phosphorylated by the phosphoenolpyruvate, (PEP)-dependent phosphotransferase system (PTS)."} {"id": "PMID:177407", "title": "Altered deoxyribonucleotide pools in P2 eductants of Escherichia coli K-12 due to deletion of the dcd gene.", "content": "Deletion of the Escherichia coli K-12 chromosome associated with P2 mediated education extend through the structural gene for uridine kinase, udk, and the dcd gene encoding 2'-deoxycytidine 5'-triphosphate deaminase. The lack of uridine kinase makes a positive selection possible for these strains. Due to the dcd mutation, P2 eductants show large alterations in their deoxyribonucleoside triphosphate pools.", "contents": "Altered deoxyribonucleotide pools in P2 eductants of Escherichia coli K-12 due to deletion of the dcd gene. Deletion of the Escherichia coli K-12 chromosome associated with P2 mediated education extend through the structural gene for uridine kinase, udk, and the dcd gene encoding 2'-deoxycytidine 5'-triphosphate deaminase. The lack of uridine kinase makes a positive selection possible for these strains. Due to the dcd mutation, P2 eductants show large alterations in their deoxyribonucleoside triphosphate pools."} {"id": "PMID:177408", "title": "Amino acid sequence of Paracoccus denitrificans cytochrome c550.", "content": "The amino acid sequence of Paracoccus (formerly Micrococcus) denitrificans cytochrome c550 has been established by a combination of standard chemical techniques and interpretation of a 2.5 A resolution x-ray electron density map. Peptides derived from a trypsin digest were chemically sequenced, and then ordered by fitting them to the density map. The amino acid compositions of chymotryptic peptides confirmed the x-ray map ordering the tryptic peptides. The amino acid sequence of this respiratory, prokaryotic cytochrome with 134 residues is discussed in relation to those of eukaryotic respiratory cytochrome c (103 to 113 amino acids), and prokaryotic, photosynthetic c2 (103 to 124 amino acids). At the primary structure level, c and c550 differ no more from cytochromes c2 than the various cytochromes c2 do from one another. It is suggested that the respiratory electron transport chain in prokaryotes and eukaryotes is a relatively late evolutionary offshoot of the photosynthetic electron transport chain in purple non-sulfur bacteria.", "contents": "Amino acid sequence of Paracoccus denitrificans cytochrome c550. The amino acid sequence of Paracoccus (formerly Micrococcus) denitrificans cytochrome c550 has been established by a combination of standard chemical techniques and interpretation of a 2.5 A resolution x-ray electron density map. Peptides derived from a trypsin digest were chemically sequenced, and then ordered by fitting them to the density map. The amino acid compositions of chymotryptic peptides confirmed the x-ray map ordering the tryptic peptides. The amino acid sequence of this respiratory, prokaryotic cytochrome with 134 residues is discussed in relation to those of eukaryotic respiratory cytochrome c (103 to 113 amino acids), and prokaryotic, photosynthetic c2 (103 to 124 amino acids). At the primary structure level, c and c550 differ no more from cytochromes c2 than the various cytochromes c2 do from one another. It is suggested that the respiratory electron transport chain in prokaryotes and eukaryotes is a relatively late evolutionary offshoot of the photosynthetic electron transport chain in purple non-sulfur bacteria."} {"id": "PMID:177409", "title": "Evidence for a phospholipid requirement in the specific binding of glucocorticoids to receptors of fibroblasts and thymic lymphocytes.", "content": "The specific steroid binding capacity of soluble preparations from mouse fibroblasts and rat thymic lymphocytes is inactivated by incubation with phospholipases. Receptor binding is drastically reduced by very low concentrations of boiled phospholipase A preparations from bee venom and snake venoms. The enzyme effect is calcium-dependent and is blocked by both phospholipid and a substrate analog that is a competitive inhibitor of phospholipase A. The specific binding capacity is also sensitive to digestion by phospholipase C. Two possible mechanisms are considered for the phospholipase A effect: (a) the receptor protein may be associated with a phospholipid component which is required for specific hormone binding; (b) phospholipase A may be producing detergent products that are indirectly inactivating the receptor. Examination of the effects of lysophosphatide on the receptor and assay of lipid phosphate in the receptor preparation do not support a mechanism based solely on detergent effects. Because phospholipase C, which does not produce detergent products, also inactivates the binding, we propose that the phospholipases may be digesting the phospholipid which is a requisite component of the glucocorticoid receptor.", "contents": "Evidence for a phospholipid requirement in the specific binding of glucocorticoids to receptors of fibroblasts and thymic lymphocytes. The specific steroid binding capacity of soluble preparations from mouse fibroblasts and rat thymic lymphocytes is inactivated by incubation with phospholipases. Receptor binding is drastically reduced by very low concentrations of boiled phospholipase A preparations from bee venom and snake venoms. The enzyme effect is calcium-dependent and is blocked by both phospholipid and a substrate analog that is a competitive inhibitor of phospholipase A. The specific binding capacity is also sensitive to digestion by phospholipase C. Two possible mechanisms are considered for the phospholipase A effect: (a) the receptor protein may be associated with a phospholipid component which is required for specific hormone binding; (b) phospholipase A may be producing detergent products that are indirectly inactivating the receptor. Examination of the effects of lysophosphatide on the receptor and assay of lipid phosphate in the receptor preparation do not support a mechanism based solely on detergent effects. Because phospholipase C, which does not produce detergent products, also inactivates the binding, we propose that the phospholipases may be digesting the phospholipid which is a requisite component of the glucocorticoid receptor."} {"id": "PMID:177410", "title": "Rat adipose tissue glycogen synthase. Evidence for multiple discrete kinetic species and their interconversion.", "content": "Rat adipose tissue glycogen synthase has been kinetically characterized. The classical D form has an apparent Km for UDP-glucose of 0.7 mM and 0.4 mM in the absence and presence of glucose 6-phosphate, respectively. The apparent Ka for glucose 6-phosphate is 0.6 mM. The effect of glucose 6-phosphate on the D form is to enhance the Vmax 7-fold. The I form is also affected by glucose 6-phosphate (Ka, 0.025 mM) but the Vmax is increased only by 20%; apparent Km values for UDP-glucose are 0.4 mM and 0.045 mM in the absence and presence of glucose 6-phosphate, respectively. In addition, two new kinetically distinguishable forms have been observed. The first, designated glycogen synthase Q, arises from an Mg2+ATP-dependent deactivation of the I form. The apparent Km values of glycogen synthase Q for UDP-glucose are identical with those of the I form; however, the apparent Ka for glucose 6-phosphate (0.2 mM) is 8-fold higher than that for the I form and one-third that for the D form. Preparations from fasted or diabetic rats contain a form of glycogen synthase, designated glycogen synthase X, that has a much lower affinity for glucose 6-phosphate than the D form (apparent Ka, 3 mM); the apparent Km values for UDP-glucose are similar to those of the D form (0.7 mM and 0.3 mM in the absence and presence of glucose 6-phosphate, respectively). In preparations from fasted rats a stepwise Mg2+-dependent conversion was demonstrated of synthase X to D to Q to I; this sequential conversion was reversed on incubation with Mg2+ATP. In preparations from fed rats, synthase Q could be generated either by limited activation (from the D form) or, after conversion to the I form, by deactivation with Mg2+ATP. However, even prolonged incubation with Mg2+ATP failed to generate the D (or X) form.", "contents": "Rat adipose tissue glycogen synthase. Evidence for multiple discrete kinetic species and their interconversion. Rat adipose tissue glycogen synthase has been kinetically characterized. The classical D form has an apparent Km for UDP-glucose of 0.7 mM and 0.4 mM in the absence and presence of glucose 6-phosphate, respectively. The apparent Ka for glucose 6-phosphate is 0.6 mM. The effect of glucose 6-phosphate on the D form is to enhance the Vmax 7-fold. The I form is also affected by glucose 6-phosphate (Ka, 0.025 mM) but the Vmax is increased only by 20%; apparent Km values for UDP-glucose are 0.4 mM and 0.045 mM in the absence and presence of glucose 6-phosphate, respectively. In addition, two new kinetically distinguishable forms have been observed. The first, designated glycogen synthase Q, arises from an Mg2+ATP-dependent deactivation of the I form. The apparent Km values of glycogen synthase Q for UDP-glucose are identical with those of the I form; however, the apparent Ka for glucose 6-phosphate (0.2 mM) is 8-fold higher than that for the I form and one-third that for the D form. Preparations from fasted or diabetic rats contain a form of glycogen synthase, designated glycogen synthase X, that has a much lower affinity for glucose 6-phosphate than the D form (apparent Ka, 3 mM); the apparent Km values for UDP-glucose are similar to those of the D form (0.7 mM and 0.3 mM in the absence and presence of glucose 6-phosphate, respectively). In preparations from fasted rats a stepwise Mg2+-dependent conversion was demonstrated of synthase X to D to Q to I; this sequential conversion was reversed on incubation with Mg2+ATP. In preparations from fed rats, synthase Q could be generated either by limited activation (from the D form) or, after conversion to the I form, by deactivation with Mg2+ATP. However, even prolonged incubation with Mg2+ATP failed to generate the D (or X) form."} {"id": "PMID:177411", "title": "Localization of the substrate and oxalacetate binding site of succinate dehydrogenase.", "content": "Succinate dehydrogenase is composed of two subunits, one of molecular weight 70,000, containing FAD in covalent linkage to a histidyl residue of the polypeptide chain, the other subunit of molecular weight 30,000. The fact that substrate, substrate analogs, and oxalacetate prevent inactivation of the enzyme by thiol-specific agents indicates that a thiol group must be present in close proximity to the flavin. Comparison of the incorporation of radioactivity into each subunit in the presence and absence of succinate or malonate shows that both substrate and competitive inhibitors protect a sulfhydryl group of the 70,000-molecular weight subunit. This indicates that a thiol group of the flavoprotein subunit is part of the active site. Similar investigations using oxalacetate as a protecting agent indicate that the tight binding of oxalacetate to the deactivated enzyme also occurs in the flavoprotein subunit, and may involve the same thiol group which is protected by succinate from alkylation by N-ethylmaleimide. It is clear, therefore, that not only the flavin site but also an essential thiol residue are located in the 70,000-molecular weight subunit. A second thiol group, located in the 30,000-molecular weight subunit, also binds N-ethylmaleimide covalently under similar conditions, without being part of the active site. Succinate, malonate, and oxalacetate do not influence the binding of this inhibitor to the thiol group of the lower molecular weight subunit. Using maleimide derivatives of nitroxide-type spin labels, it has been possible to demonstrate the presence of two types of thiol groups in the enzyme which form covalent derivatives with the spin probe. When the enzyme is treated with an equimolar quantity of the spin probe, a largely isotropic electron spin resonance spectrum is obtained, indicating a high probe mobility. When this site is first blocked by treating the enzyme with an equimolar quantity of N-ethylmaleimide, followed by an equimolar amount of spin label, the label is strongly immobilized with a splitting of 64 gauss. It is suggested that the sulfhydryl group which is involved in the immobilized species is at the active site.", "contents": "Localization of the substrate and oxalacetate binding site of succinate dehydrogenase. Succinate dehydrogenase is composed of two subunits, one of molecular weight 70,000, containing FAD in covalent linkage to a histidyl residue of the polypeptide chain, the other subunit of molecular weight 30,000. The fact that substrate, substrate analogs, and oxalacetate prevent inactivation of the enzyme by thiol-specific agents indicates that a thiol group must be present in close proximity to the flavin. Comparison of the incorporation of radioactivity into each subunit in the presence and absence of succinate or malonate shows that both substrate and competitive inhibitors protect a sulfhydryl group of the 70,000-molecular weight subunit. This indicates that a thiol group of the flavoprotein subunit is part of the active site. Similar investigations using oxalacetate as a protecting agent indicate that the tight binding of oxalacetate to the deactivated enzyme also occurs in the flavoprotein subunit, and may involve the same thiol group which is protected by succinate from alkylation by N-ethylmaleimide. It is clear, therefore, that not only the flavin site but also an essential thiol residue are located in the 70,000-molecular weight subunit. A second thiol group, located in the 30,000-molecular weight subunit, also binds N-ethylmaleimide covalently under similar conditions, without being part of the active site. Succinate, malonate, and oxalacetate do not influence the binding of this inhibitor to the thiol group of the lower molecular weight subunit. Using maleimide derivatives of nitroxide-type spin labels, it has been possible to demonstrate the presence of two types of thiol groups in the enzyme which form covalent derivatives with the spin probe. When the enzyme is treated with an equimolar quantity of the spin probe, a largely isotropic electron spin resonance spectrum is obtained, indicating a high probe mobility. When this site is first blocked by treating the enzyme with an equimolar quantity of N-ethylmaleimide, followed by an equimolar amount of spin label, the label is strongly immobilized with a splitting of 64 gauss. It is suggested that the sulfhydryl group which is involved in the immobilized species is at the active site."} {"id": "PMID:177412", "title": "Increased intestinal chromatin template activity. Influence of 1alpha,25-dihydroxyvitamin D3 and hormone-receptor complexes.", "content": "1alpha,25-Dihydroxyvitamin D3 administration to rachitic chicks results in an increase in the chromatin template activity of intestinal target tissue assayed in vitro using Escherichia coli RNA polymerase. The maximum stimulation of template capacity was 12 to 20% over control values and occurred 2 hours after administration of the sterol. This rapid effect preceded the biologic response to 1alpha,25-dihydroxyvitamin D3 in the intestine and was not observed in other tissues such as liver or kidney. The in vivo enhancement of intestinal chromatin template activity was specific for the 1alpha,25-dihydroxyvitamin D3 hormone in that equivalent doses of 25-hydroxyvitamin D3 or vitamin D3 did not elicit a response in 2 to 3 hours. Only 1alpha-hydroxyvitamin D3, a synthetic sterol which is very rapidly metabolized to the 1alpha,25-dihydroxyvitamin D3 form, was able to minic the natural hormone in vivo. To further elucidate the nuclear mechanism of action of 1alpha,25-dihydroxyvitamin D3, the hormone was preincubated at 0 degrees with intestinal cytosol to form hormone-receptor complexes. After addition of the hormone-receptor complexes to purified intestinal mucosa nuclei and incubation for 1 hour at 25 degrees, chromatin isolated from this reconstituted system displayed a significant increase in template activity as compared to chromatin prepared from similar in vitro incubations not containing hormone. This stimulation was 12 to 24% over control values and exhibited an absolute requirement for intestinal cell cytosol. The response was specific for physiologic levels of 1alpha,25-dihydroxyvitamin D3, but occurred with pharmacologic doses of 25-hydroxyvitamin D3. It is concluded that a stimulation of the chromatin template activity of intestinal target tissue by 1alpha,25-dihydroxyvitamin D3 may be an integral part of the ultimate physiologic response of enhanced calcium transport.", "contents": "Increased intestinal chromatin template activity. Influence of 1alpha,25-dihydroxyvitamin D3 and hormone-receptor complexes. 1alpha,25-Dihydroxyvitamin D3 administration to rachitic chicks results in an increase in the chromatin template activity of intestinal target tissue assayed in vitro using Escherichia coli RNA polymerase. The maximum stimulation of template capacity was 12 to 20% over control values and occurred 2 hours after administration of the sterol. This rapid effect preceded the biologic response to 1alpha,25-dihydroxyvitamin D3 in the intestine and was not observed in other tissues such as liver or kidney. The in vivo enhancement of intestinal chromatin template activity was specific for the 1alpha,25-dihydroxyvitamin D3 hormone in that equivalent doses of 25-hydroxyvitamin D3 or vitamin D3 did not elicit a response in 2 to 3 hours. Only 1alpha-hydroxyvitamin D3, a synthetic sterol which is very rapidly metabolized to the 1alpha,25-dihydroxyvitamin D3 form, was able to minic the natural hormone in vivo. To further elucidate the nuclear mechanism of action of 1alpha,25-dihydroxyvitamin D3, the hormone was preincubated at 0 degrees with intestinal cytosol to form hormone-receptor complexes. After addition of the hormone-receptor complexes to purified intestinal mucosa nuclei and incubation for 1 hour at 25 degrees, chromatin isolated from this reconstituted system displayed a significant increase in template activity as compared to chromatin prepared from similar in vitro incubations not containing hormone. This stimulation was 12 to 24% over control values and exhibited an absolute requirement for intestinal cell cytosol. The response was specific for physiologic levels of 1alpha,25-dihydroxyvitamin D3, but occurred with pharmacologic doses of 25-hydroxyvitamin D3. It is concluded that a stimulation of the chromatin template activity of intestinal target tissue by 1alpha,25-dihydroxyvitamin D3 may be an integral part of the ultimate physiologic response of enhanced calcium transport."} {"id": "PMID:177413", "title": "Interaction of swine lipoproteins with the low density lipoprotein receptor in human fibroblasts.", "content": "HDLc, a cholesterol-rich lipoprotein that accumulates in the plasma of cholesterol-fed swine, was shown to resemble functionally human and swine low density lipoprotein in its ability to bind to the low density lipoprotein receptor in monolayers of cultured human fibroblasts. This binding occurred even though HDLc lacked detectable apoprotein B, which is the major protein of low density lipoprotein. After it was bound to the low density lipoprotein receptor, HDLc, like human and swine low density lipoprotein, delivered its cholesterol to the cells, and this, in turn, caused a suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, an activation of the cholesterol-esterifying system, and a net accumulation of free and esterified cholesterol within the cells. Swine HDLc, like human high density lipoprotein, did not bind to the low density lipoprotein receptor nor did it elicit any of the subsequent metabolic events. HDLc, like human low density lipoprotein, was incapable of producing a metabolic effect in fibroblasts derived from a subject with the homozygous form of familial hypercholesterolemia, which lack low density lipoprotein receptors. These results indicate that two lipoproteins that have been associated with athersclerosis--low density lipoprotein in humans and HDLc in cholesterol-fed swine--both can cause the accumulation of cholesterol and cholesteryl esters within cells through an interaction with the low density lipoprotein receptor.", "contents": "Interaction of swine lipoproteins with the low density lipoprotein receptor in human fibroblasts. HDLc, a cholesterol-rich lipoprotein that accumulates in the plasma of cholesterol-fed swine, was shown to resemble functionally human and swine low density lipoprotein in its ability to bind to the low density lipoprotein receptor in monolayers of cultured human fibroblasts. This binding occurred even though HDLc lacked detectable apoprotein B, which is the major protein of low density lipoprotein. After it was bound to the low density lipoprotein receptor, HDLc, like human and swine low density lipoprotein, delivered its cholesterol to the cells, and this, in turn, caused a suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, an activation of the cholesterol-esterifying system, and a net accumulation of free and esterified cholesterol within the cells. Swine HDLc, like human high density lipoprotein, did not bind to the low density lipoprotein receptor nor did it elicit any of the subsequent metabolic events. HDLc, like human low density lipoprotein, was incapable of producing a metabolic effect in fibroblasts derived from a subject with the homozygous form of familial hypercholesterolemia, which lack low density lipoprotein receptors. These results indicate that two lipoproteins that have been associated with athersclerosis--low density lipoprotein in humans and HDLc in cholesterol-fed swine--both can cause the accumulation of cholesterol and cholesteryl esters within cells through an interaction with the low density lipoprotein receptor."} {"id": "PMID:177414", "title": "Nuclear magnetic relaxation studies of the conformation of adenosine 5'-triphosphate on pyruvate kinase from rabbit muscle.", "content": "The conformation of adenosine 5'-triphosphate in the manganese complex of pyruvate kinase from rabbit muscle was determined from six metal to nucleus distances derived by nuclear magnetic relaxation techniques. On the enzyme, no direct metal-ATP coordination exists. The phosphorous atoms of ATP are 4.9 to 5.1 A away from manganese, a distance which indicates either a predominantly (greater than or equal to 94%) second sphere complex or, less likely, a highly distorted inner sphere complex. Thus, water ligands or ligands from the protein might intervene between the ATP molecule and the divalent metal ion and facilitate their interaction. The metal-gammaP distance of 5 A for pyruvate kinase-bound ATP is equal to that found for the phosphorous atom of phosphoenolpyruvate and cobalt(II) on pyruvate kinase (Melamud, E., and Mildvan, A. S. (1975) J. Biol. Chem. 250, 8193-8201), which is consistent with the overlap in space of the P-enolpyruvate-phosphorus and the gammaP of ATP at the active site. This observation explains the competitive binding of these two substrates to the enzyme, as detected by NMR and by early kinetic studies. From the phosphorus data and from measurements of the relaxation rates of 3 protons of ATP in the pyruvate kinase-metal-ATP complex, the conformation of ATP was characterized as extended with distances of 6.0, 9.1, and 7.5 A from manganese to the H8, H2, and H'1 protons, respectively. The torsion angle about the glycosidic bond (chi) which defines the conformation of the enzyme-bound riboside and adenine rings was determined to be 30 degrees. In contrast, the conformation of the binary Mn(II)-ATP complex in solution is folded around the metal with direct manganese coordination of the alpha-, beta-, and gamma-phosphorus atoms, and with metal to proton distances of 4.5, 6.4, and 6.2 A for the H8, H2, and H'1 protons, suggesting a second sphere manganese-adenine interaction. The chi angle equals 90 degrees for the binary complex primarily because of the metal-base interaction. Thus, a profound change in the conformation and structure of Mn(II)-ATP from a folded chelate to an extended second sphere complex results when the nucleotide binds to pyruvate kinase.", "contents": "Nuclear magnetic relaxation studies of the conformation of adenosine 5'-triphosphate on pyruvate kinase from rabbit muscle. The conformation of adenosine 5'-triphosphate in the manganese complex of pyruvate kinase from rabbit muscle was determined from six metal to nucleus distances derived by nuclear magnetic relaxation techniques. On the enzyme, no direct metal-ATP coordination exists. The phosphorous atoms of ATP are 4.9 to 5.1 A away from manganese, a distance which indicates either a predominantly (greater than or equal to 94%) second sphere complex or, less likely, a highly distorted inner sphere complex. Thus, water ligands or ligands from the protein might intervene between the ATP molecule and the divalent metal ion and facilitate their interaction. The metal-gammaP distance of 5 A for pyruvate kinase-bound ATP is equal to that found for the phosphorous atom of phosphoenolpyruvate and cobalt(II) on pyruvate kinase (Melamud, E., and Mildvan, A. S. (1975) J. Biol. Chem. 250, 8193-8201), which is consistent with the overlap in space of the P-enolpyruvate-phosphorus and the gammaP of ATP at the active site. This observation explains the competitive binding of these two substrates to the enzyme, as detected by NMR and by early kinetic studies. From the phosphorus data and from measurements of the relaxation rates of 3 protons of ATP in the pyruvate kinase-metal-ATP complex, the conformation of ATP was characterized as extended with distances of 6.0, 9.1, and 7.5 A from manganese to the H8, H2, and H'1 protons, respectively. The torsion angle about the glycosidic bond (chi) which defines the conformation of the enzyme-bound riboside and adenine rings was determined to be 30 degrees. In contrast, the conformation of the binary Mn(II)-ATP complex in solution is folded around the metal with direct manganese coordination of the alpha-, beta-, and gamma-phosphorus atoms, and with metal to proton distances of 4.5, 6.4, and 6.2 A for the H8, H2, and H'1 protons, suggesting a second sphere manganese-adenine interaction. The chi angle equals 90 degrees for the binary complex primarily because of the metal-base interaction. Thus, a profound change in the conformation and structure of Mn(II)-ATP from a folded chelate to an extended second sphere complex results when the nucleotide binds to pyruvate kinase."} {"id": "PMID:177415", "title": "Chromium(III)-adenosine triphosphate as a paramagnetic probe to determine intersubstrate distances on pyruvate kinase. Detection of an active enzyme-metal-ATP-metal complex.", "content": "The interaction of CrATP, a stable, substitution-inert, paramagnetic tridentate complex of ATP, with muscle pyruvate kinase has been studied by measuring the effects of CrATP on the kinetics of pyruvate enolization and on the longitudinal nuclear magnetic relaxation rate (1/T1) of the protons of water and the protons and carbon atoms of pyruvate to investigate the existence and activity of bimetallic enzyme-M(II)-CrATP complexes and to determine intersubstrate distances on a kinase. The paramagnetic effect of CrATP on 1/T1 of water protons is enhanced upon complexation with the enzyme. Titrations of the enzyme with CrATP yielded characteristic enhancements of 1/T1 for the binary enzyme-CrATP, ternary enzyme-Mg(II)-crATP, and quaternary enzyme-Mg(II)-crATP-pyruvate complexes of 3.5, 1.7, and 1.2 and dissociation constants of CrATP of 400, 200, and 200 muM, respectively. From the frequency dependence of 1/T1, the number of fast exchanging water protons in the coordination spheres of Cr(III) is approximately 6 in CrATP and in both the ternary enzyme-Mg(II)-CrATP complex and the quaternary enzyme-Mg(II)-CrATP-pyruvate complex. The paramagnetic effect of enzyme-bound Mn(II) on 1/T1 of water protons decreases upon the addition of CrATP. Titration of the binary enzyme-Mn(II) complex with CrATP decreases the characteristic enhancement due to Mn(II) from 24 +/- 3 to 6 +/- 1. Titration of the ternary eznyme-Mn(II)-pyruvate complex with CrATP decreases the enhancement from 6 +/- 1 to 0.5 +/- 0.1. The affinity of the enzyme for Mn(II) is increased 2-fold upon binding of CrATP as indicated by decreases in the amplitude of the EPR spectrum of free Mn(II). The dissociation constants of CrATP from the enzyme-Mn(II)-CrATP complex, the enzyme-CrATP-pyruvate complex, and the enzyme-Mn(II)-CrATP-pyruvate complex are all 200 muM. The observed titration behavior, the characteristic enhancement values, the tightening by Mg(II) of the binding of CrATP to the enzyme, and the tightening of the binding of Mn(II) to the enzyme by CrATP establish the existence of enzyme-M(II)-CrATP and enzyme-M(II)-CrATP-pyruvate complexes containing two cations, Mg(II) or Mn(II) and Cr(III), at the active site.", "contents": "Chromium(III)-adenosine triphosphate as a paramagnetic probe to determine intersubstrate distances on pyruvate kinase. Detection of an active enzyme-metal-ATP-metal complex. The interaction of CrATP, a stable, substitution-inert, paramagnetic tridentate complex of ATP, with muscle pyruvate kinase has been studied by measuring the effects of CrATP on the kinetics of pyruvate enolization and on the longitudinal nuclear magnetic relaxation rate (1/T1) of the protons of water and the protons and carbon atoms of pyruvate to investigate the existence and activity of bimetallic enzyme-M(II)-CrATP complexes and to determine intersubstrate distances on a kinase. The paramagnetic effect of CrATP on 1/T1 of water protons is enhanced upon complexation with the enzyme. Titrations of the enzyme with CrATP yielded characteristic enhancements of 1/T1 for the binary enzyme-CrATP, ternary enzyme-Mg(II)-crATP, and quaternary enzyme-Mg(II)-crATP-pyruvate complexes of 3.5, 1.7, and 1.2 and dissociation constants of CrATP of 400, 200, and 200 muM, respectively. From the frequency dependence of 1/T1, the number of fast exchanging water protons in the coordination spheres of Cr(III) is approximately 6 in CrATP and in both the ternary enzyme-Mg(II)-CrATP complex and the quaternary enzyme-Mg(II)-CrATP-pyruvate complex. The paramagnetic effect of enzyme-bound Mn(II) on 1/T1 of water protons decreases upon the addition of CrATP. Titration of the binary enzyme-Mn(II) complex with CrATP decreases the characteristic enhancement due to Mn(II) from 24 +/- 3 to 6 +/- 1. Titration of the ternary eznyme-Mn(II)-pyruvate complex with CrATP decreases the enhancement from 6 +/- 1 to 0.5 +/- 0.1. The affinity of the enzyme for Mn(II) is increased 2-fold upon binding of CrATP as indicated by decreases in the amplitude of the EPR spectrum of free Mn(II). The dissociation constants of CrATP from the enzyme-Mn(II)-CrATP complex, the enzyme-CrATP-pyruvate complex, and the enzyme-Mn(II)-CrATP-pyruvate complex are all 200 muM. The observed titration behavior, the characteristic enhancement values, the tightening by Mg(II) of the binding of CrATP to the enzyme, and the tightening of the binding of Mn(II) to the enzyme by CrATP establish the existence of enzyme-M(II)-CrATP and enzyme-M(II)-CrATP-pyruvate complexes containing two cations, Mg(II) or Mn(II) and Cr(III), at the active site."} {"id": "PMID:177416", "title": "Purification and properties of the proton-translocating adenosine triphosphatase complex of bovine heart mitochondria.", "content": "1. The proton-translocating adenosine triphosphatase (ATPase) of bovine heart mitochondria was highly purified by extraction of submitochondrial particles with cholate, fractionation with ammonium sulfate, and sucrose gradient centrifugation in the presence of methanol, deoxycholate, and lysolecithin. 2. The preparation had a very low content of phospholipids, respiratory components, and adenine nucleotide transporter. The ATPase activity (14 o 16 micromoles/min/mg at 30 degrees) was dependent on addition of phospholipids. The purified enzyme was reconstituted with phospholipids, coupling factor 1 (F1), and the oligomycin sensitivity-conferring protein (OSCP) yielding vesicles with highly active 32Pi-ATP exchange (up to 260 nanomoles/min/mg at 30 degrees), and a proton pump driven by ATP. Site III oxidative phosphorylation was reconstituted when purified cytochrome oxidase was included. 3. The 32Pi-ATP exchange of the reconstituted vesicles was sensitive to both rutamycin and dichylohexylcarbodiimide but the ATPase activity was sensitive to rutamycin and not to dicyclohexylcarbodiimide. 4. In sodium dodecyl sulfate-acrylamide gel scans of the complex, the subunits of F1, OSCP, and three other major bands with apparent molecular weights of 32,000, 23,000, and about 11,000 were noted. Three other minor bands with estimated molecular weights of 80,000, 70,000, and 52,000 were also detected. These bands apparently represent residual trace amounts of respiratory components. Quantitative assays of individual respiratory components revealed between 0 and 3% contamination. 5. We conclude that the rutamycin-sensitive ATPase complex functions as a reversible ATP-driven proton pump.", "contents": "Purification and properties of the proton-translocating adenosine triphosphatase complex of bovine heart mitochondria. 1. The proton-translocating adenosine triphosphatase (ATPase) of bovine heart mitochondria was highly purified by extraction of submitochondrial particles with cholate, fractionation with ammonium sulfate, and sucrose gradient centrifugation in the presence of methanol, deoxycholate, and lysolecithin. 2. The preparation had a very low content of phospholipids, respiratory components, and adenine nucleotide transporter. The ATPase activity (14 o 16 micromoles/min/mg at 30 degrees) was dependent on addition of phospholipids. The purified enzyme was reconstituted with phospholipids, coupling factor 1 (F1), and the oligomycin sensitivity-conferring protein (OSCP) yielding vesicles with highly active 32Pi-ATP exchange (up to 260 nanomoles/min/mg at 30 degrees), and a proton pump driven by ATP. Site III oxidative phosphorylation was reconstituted when purified cytochrome oxidase was included. 3. The 32Pi-ATP exchange of the reconstituted vesicles was sensitive to both rutamycin and dichylohexylcarbodiimide but the ATPase activity was sensitive to rutamycin and not to dicyclohexylcarbodiimide. 4. In sodium dodecyl sulfate-acrylamide gel scans of the complex, the subunits of F1, OSCP, and three other major bands with apparent molecular weights of 32,000, 23,000, and about 11,000 were noted. Three other minor bands with estimated molecular weights of 80,000, 70,000, and 52,000 were also detected. These bands apparently represent residual trace amounts of respiratory components. Quantitative assays of individual respiratory components revealed between 0 and 3% contamination. 5. We conclude that the rutamycin-sensitive ATPase complex functions as a reversible ATP-driven proton pump."} {"id": "PMID:177417", "title": "Involvement of the glucose enzymes II of the sugar phosphotransferase system in the regulation of adenylate cyclase by glucose in Escherichia coli.", "content": "The nature of the interaction of glucose with toluene-treated cells of Escherichia coli leading to inhibition of adenylate cyclase was examined by the use of analogues. Those analogues with variations of the substituents about carbon atoms 1 or 2 (e.g. alpha-methylglucoside or 2-deoxyglucose) are inhibitory, and they are also substrates of the phosphoenolpyruvate-dependent sugar phosphotransferase system. Analogues with changes in other parts of the molecule (e.g. 3-O-methylglucose or galactose), L-glucose and several disaccharides and pentoses, do not inhibit adenylate cyclase and are not substrates of the phosphotransferase system. This correlation suggests some functional relationship between the adenylate cyclase and phosphotransferase systems. Further studies were done with mutants defective in glucose enzymes II of the phosphotransferase system (designated GPT and MPT); these two activities are measured by phosphorylation of alpha-methyl-glucoside and 2-deoxyglucose, respectively. The wild-type parent phosphorylates both analogues, and both inhibit adenylate cyclase. In the GPT- mutant, alpha-methylglucoside does not inhibit adenylate cyclase and is not phosphorylated, while 2-deoxyglucose is inhibitory and phosphorylated. In the GPT- MPT- double mutant, adenylate cyclase activity is present, but neither alpha-methylglucoside nor 2-deoxyglucose inhibits adenylate cyclase, and neither sugar is phosphorylated. These studies demonstrate that glucose inhibition of adenylate cyclase in toluene-treated cells requires an interaction of this sugar with either the GPT or mpt enzyme II of the phosphotransferase system.", "contents": "Involvement of the glucose enzymes II of the sugar phosphotransferase system in the regulation of adenylate cyclase by glucose in Escherichia coli. The nature of the interaction of glucose with toluene-treated cells of Escherichia coli leading to inhibition of adenylate cyclase was examined by the use of analogues. Those analogues with variations of the substituents about carbon atoms 1 or 2 (e.g. alpha-methylglucoside or 2-deoxyglucose) are inhibitory, and they are also substrates of the phosphoenolpyruvate-dependent sugar phosphotransferase system. Analogues with changes in other parts of the molecule (e.g. 3-O-methylglucose or galactose), L-glucose and several disaccharides and pentoses, do not inhibit adenylate cyclase and are not substrates of the phosphotransferase system. This correlation suggests some functional relationship between the adenylate cyclase and phosphotransferase systems. Further studies were done with mutants defective in glucose enzymes II of the phosphotransferase system (designated GPT and MPT); these two activities are measured by phosphorylation of alpha-methyl-glucoside and 2-deoxyglucose, respectively. The wild-type parent phosphorylates both analogues, and both inhibit adenylate cyclase. In the GPT- mutant, alpha-methylglucoside does not inhibit adenylate cyclase and is not phosphorylated, while 2-deoxyglucose is inhibitory and phosphorylated. In the GPT- MPT- double mutant, adenylate cyclase activity is present, but neither alpha-methylglucoside nor 2-deoxyglucose inhibits adenylate cyclase, and neither sugar is phosphorylated. These studies demonstrate that glucose inhibition of adenylate cyclase in toluene-treated cells requires an interaction of this sugar with either the GPT or mpt enzyme II of the phosphotransferase system."} {"id": "PMID:177418", "title": "Deoxythymidine kinase induced in HeLa TK- cells by herpes simplex virus type I and type II. II. Purification and characterization.", "content": "Deoxythymidine kinase activities were induced in HeLa TK- (deoxythymidine kinase-deficient) cells infected with either herpes simplex virus type I or herpes simplex virus type II. The herpes simplex virus type I-induced enzyme was found in the cytoplasmic and nuclear fractions of the infected cells, whereas the herpes simplex type II-induced deoxythymidine kinase could only be found in the cytoplasm. Herpes simplex virus type I and II specific deoxythymidine kinases were purified by affinity column chromatography. Both purified deoxythymidine kinases retained the deoxycytidine kinase activity present in the crude preparation. The purified herpes simplex virus type I deoxythymidine kinase had a different mobility on electrophoresis, but the same sedimentation rate on a glycerol gradient as the corresponding unpurified enzyme, whereas the purified herpes simplex virus type II deoxythymidine kinase had the same mobility and sedimentation rate as the corresponding unpurified enzyme. In the presence of Mg2+ATP and dithiothreitol, herpes simplex virus type II deoxythymidine kinase was more stable than herpes simplex virus type I deoxythymidine kinase at both 45 degrees and 4 degrees. The deoxycytidine kinase activity present in the purified preparations was inactivated at the same rate as the deoxythymidine kinase activity. In the presence of the other substrate, deoxythymidine, herpes simplex virus type I deoxythymidine kinase was more stable than herpes simplex virus type II kinase. The purified herpes simplex virus type I and II deoxythymidine kinase had different activation energies when Mg2+ATP and deoxythymidine were used as substrates, but showed the same sensitivity toward ammonium sulfate inhibition.", "contents": "Deoxythymidine kinase induced in HeLa TK- cells by herpes simplex virus type I and type II. II. Purification and characterization. Deoxythymidine kinase activities were induced in HeLa TK- (deoxythymidine kinase-deficient) cells infected with either herpes simplex virus type I or herpes simplex virus type II. The herpes simplex virus type I-induced enzyme was found in the cytoplasmic and nuclear fractions of the infected cells, whereas the herpes simplex type II-induced deoxythymidine kinase could only be found in the cytoplasm. Herpes simplex virus type I and II specific deoxythymidine kinases were purified by affinity column chromatography. Both purified deoxythymidine kinases retained the deoxycytidine kinase activity present in the crude preparation. The purified herpes simplex virus type I deoxythymidine kinase had a different mobility on electrophoresis, but the same sedimentation rate on a glycerol gradient as the corresponding unpurified enzyme, whereas the purified herpes simplex virus type II deoxythymidine kinase had the same mobility and sedimentation rate as the corresponding unpurified enzyme. In the presence of Mg2+ATP and dithiothreitol, herpes simplex virus type II deoxythymidine kinase was more stable than herpes simplex virus type I deoxythymidine kinase at both 45 degrees and 4 degrees. The deoxycytidine kinase activity present in the purified preparations was inactivated at the same rate as the deoxythymidine kinase activity. In the presence of the other substrate, deoxythymidine, herpes simplex virus type I deoxythymidine kinase was more stable than herpes simplex virus type II kinase. The purified herpes simplex virus type I and II deoxythymidine kinase had different activation energies when Mg2+ATP and deoxythymidine were used as substrates, but showed the same sensitivity toward ammonium sulfate inhibition."} {"id": "PMID:177419", "title": "The reduced nicotinamide adenine dinucleotide-activated phosphoenolpyruvate carboxylase from Pseudomonas MA. Correlation of allosteric properties with changes in the sedimentation behavior.", "content": "Phosphoenolpyruvate carboxylase from Pseudomonas MA, grown on methylamine as a sole carbon source, has been studied with respect to some of its regulatory properties. The enzyme shows both negative and positive cooperativity with respect to the substrate phosphoenolpyruvate (Hill coefficients of 0.5 and 1.75). The enzyme requires a divalent cation for activity. Either magnesium or manganous ion is effective. While magnesium shows normal kinetics, manganous ion shows positive cooperativity with a Hill coefficient of 1.4. The enzyme is activated 50-fold by 0.2 mM NADH at 1 mM phosphoenolpyruvate. This activation is hysteretic, showing a lag of 2 to 3 min. Both NADH and Mn2+ induce a change in the sedimentation coefficient of the enzyme from 12.4 to 8.5 as measured by sucrose density gradient centrifugation. High concentrations of phosphate or sulfate are capable of producing this effect on sedimentation, but neither will activate more than 3-fold. Thus, if NADH is an indicator of the total energy level of the cell, the enzyme appears to be susceptible to control by factors which reflect this total energy level. The importance of this control with respect to hypothetical pathways of carbon utilization in the organism is discussed.", "contents": "The reduced nicotinamide adenine dinucleotide-activated phosphoenolpyruvate carboxylase from Pseudomonas MA. Correlation of allosteric properties with changes in the sedimentation behavior. Phosphoenolpyruvate carboxylase from Pseudomonas MA, grown on methylamine as a sole carbon source, has been studied with respect to some of its regulatory properties. The enzyme shows both negative and positive cooperativity with respect to the substrate phosphoenolpyruvate (Hill coefficients of 0.5 and 1.75). The enzyme requires a divalent cation for activity. Either magnesium or manganous ion is effective. While magnesium shows normal kinetics, manganous ion shows positive cooperativity with a Hill coefficient of 1.4. The enzyme is activated 50-fold by 0.2 mM NADH at 1 mM phosphoenolpyruvate. This activation is hysteretic, showing a lag of 2 to 3 min. Both NADH and Mn2+ induce a change in the sedimentation coefficient of the enzyme from 12.4 to 8.5 as measured by sucrose density gradient centrifugation. High concentrations of phosphate or sulfate are capable of producing this effect on sedimentation, but neither will activate more than 3-fold. Thus, if NADH is an indicator of the total energy level of the cell, the enzyme appears to be susceptible to control by factors which reflect this total energy level. The importance of this control with respect to hypothetical pathways of carbon utilization in the organism is discussed."} {"id": "PMID:177420", "title": "Vitamin K-dependent carboxylase. Requirements of the rat liver microsomal enzyme system.", "content": "Vitamin K is required in an enzymatic reaction which carboxylates glutamyl residues in a microsomal protein precursor of plasma prothrombin to form gamma-carboxyglutamic acid residues. The partial requirements of this microsomal, vitamin K-dependent carboxylase system have been determined. A requirement of the system for cytosolic factors appears to be due primarily to the presence of reduced pyridine nucleotides or a reduced pyridine nucleotide-generating system in the cytosol. The hydroquinone of vitamin K has been demonstrated to be the enzymatically active form of the vitamin. When vitamin K1 hydroquinone is added to the carboxylase system, no NAD(P)H is needed for maximum activity. The carboxylase activity is half-maximally stimulated by 0.25 mug of vitamin K1/ml in the presence of cytosolic components but requires at least 10 times as much vitamin when microsomes are incubated in a cytosol-free buffer. Menadione is inactive as a vitamin source in this system, and the carboxylase activity is inhibited by the 2-chloro analog of vitamin K1 and by Warfarin. The ATP analog, AMP-P(NH)P, inhibited the carboxylase activity, but a dependence on exogenous ATP or an ATP-generating system could not be demonstrated. Carboxylase activity was found to be dependent on an O2-containing gas phase, and upon the HCO3- concentration.", "contents": "Vitamin K-dependent carboxylase. Requirements of the rat liver microsomal enzyme system. Vitamin K is required in an enzymatic reaction which carboxylates glutamyl residues in a microsomal protein precursor of plasma prothrombin to form gamma-carboxyglutamic acid residues. The partial requirements of this microsomal, vitamin K-dependent carboxylase system have been determined. A requirement of the system for cytosolic factors appears to be due primarily to the presence of reduced pyridine nucleotides or a reduced pyridine nucleotide-generating system in the cytosol. The hydroquinone of vitamin K has been demonstrated to be the enzymatically active form of the vitamin. When vitamin K1 hydroquinone is added to the carboxylase system, no NAD(P)H is needed for maximum activity. The carboxylase activity is half-maximally stimulated by 0.25 mug of vitamin K1/ml in the presence of cytosolic components but requires at least 10 times as much vitamin when microsomes are incubated in a cytosol-free buffer. Menadione is inactive as a vitamin source in this system, and the carboxylase activity is inhibited by the 2-chloro analog of vitamin K1 and by Warfarin. The ATP analog, AMP-P(NH)P, inhibited the carboxylase activity, but a dependence on exogenous ATP or an ATP-generating system could not be demonstrated. Carboxylase activity was found to be dependent on an O2-containing gas phase, and upon the HCO3- concentration."} {"id": "PMID:177421", "title": "Magnetic resonance study of the three-dimensional structure of creatine kinase-substrate complexes. Implications for substrate specificity and catalytic mechanism.", "content": "The paramagnetic effects of the bound manganese ion and of a covalently attached spin label on proton nuclear spin relaxation rates have been used to calculate distances for a structural model of the MnADP and creatine complexed to creatine kinase from rabbit muscle. The nucleotide and guanidino substrates are so aligned on the enzyme that the transferable phosphoryl group on one substrate is in apposition to the acceptor moiety on the second substrate. The divalent metal ion is most probably liganded to the alpha and beta phosphates of the nucleotide substrate, both in the abortive MnADP-creatine-enzyme complex and in the active MnATP-creatine-enzyme complex. The metal ion-formate distance approximately 5 A in the Mn(II)ADP-formate-creatine-enzyme complex and less than 5 A in the Co(II)ADP-formate-creatine-enzyme complex is consistent with the suggestion that the monovalent anion is binding at the site normally occupied by the transferable phosphoryl group, thus producing a complex which mimics the transition state. Although only an upper limit of the distance from Mn(II) to the guanidino substrate could be determined in the presence of formate, it could be concluded that the disposition of the guanidino substrate changes upon addition of formate, since the relative distances of the methyl and methylene group are inverted. The effect of formate and nitrate on increasing the residence time of creatine in the MnADP-creatine-enzyme complex as determined by NMR provides evidence that the complexes observed by NMR are identical with those involved in the catalytic mechanism, since a parallel effect of formate and nitrate is observed in the kinetics of the enzymatic reaction, where the dissociation constant of creatine from the abortive quaternary complex decreases in the presence of the anions as had been determined from their inhibition of the forward reaction (Milner-White, E.J., and Watts, D.C. (1971) Biochem. J. 122, 727-740). Although the guanidino substrate is not directly liganded to the divalent metal ion, the electron paramagnetic resonance spectrum of manganese in the transition state analog complexes, i.e. nitrate-ADP-guanidino substrate-enzyme, is strongly dependent on catalytic activity of the guanidino substrate. The structural differences observed by EPR among transition state analog complexes with various guanidino substrates were not reflected in distances from Mn(II) to the guanidino substrate, which were 10% and 0.3% as active as creatine. Within the experimental error of 1 A, the distances were the same. The enzyme or the enzyme-substrate complexes may be considered to exist in a number of structurally distinct conformations in equilibrium based on the EPR spectra and on the anomalous temperature-dependence of the relaxation rates of the formate proton of the transition state analog complexes...", "contents": "Magnetic resonance study of the three-dimensional structure of creatine kinase-substrate complexes. Implications for substrate specificity and catalytic mechanism. The paramagnetic effects of the bound manganese ion and of a covalently attached spin label on proton nuclear spin relaxation rates have been used to calculate distances for a structural model of the MnADP and creatine complexed to creatine kinase from rabbit muscle. The nucleotide and guanidino substrates are so aligned on the enzyme that the transferable phosphoryl group on one substrate is in apposition to the acceptor moiety on the second substrate. The divalent metal ion is most probably liganded to the alpha and beta phosphates of the nucleotide substrate, both in the abortive MnADP-creatine-enzyme complex and in the active MnATP-creatine-enzyme complex. The metal ion-formate distance approximately 5 A in the Mn(II)ADP-formate-creatine-enzyme complex and less than 5 A in the Co(II)ADP-formate-creatine-enzyme complex is consistent with the suggestion that the monovalent anion is binding at the site normally occupied by the transferable phosphoryl group, thus producing a complex which mimics the transition state. Although only an upper limit of the distance from Mn(II) to the guanidino substrate could be determined in the presence of formate, it could be concluded that the disposition of the guanidino substrate changes upon addition of formate, since the relative distances of the methyl and methylene group are inverted. The effect of formate and nitrate on increasing the residence time of creatine in the MnADP-creatine-enzyme complex as determined by NMR provides evidence that the complexes observed by NMR are identical with those involved in the catalytic mechanism, since a parallel effect of formate and nitrate is observed in the kinetics of the enzymatic reaction, where the dissociation constant of creatine from the abortive quaternary complex decreases in the presence of the anions as had been determined from their inhibition of the forward reaction (Milner-White, E.J., and Watts, D.C. (1971) Biochem. J. 122, 727-740). Although the guanidino substrate is not directly liganded to the divalent metal ion, the electron paramagnetic resonance spectrum of manganese in the transition state analog complexes, i.e. nitrate-ADP-guanidino substrate-enzyme, is strongly dependent on catalytic activity of the guanidino substrate. The structural differences observed by EPR among transition state analog complexes with various guanidino substrates were not reflected in distances from Mn(II) to the guanidino substrate, which were 10% and 0.3% as active as creatine. Within the experimental error of 1 A, the distances were the same. The enzyme or the enzyme-substrate complexes may be considered to exist in a number of structurally distinct conformations in equilibrium based on the EPR spectra and on the anomalous temperature-dependence of the relaxation rates of the formate proton of the transition state analog complexes..."} {"id": "PMID:177422", "title": "Characterization of a cytochrome P-450-dependent steroid hydroxylase system present in Bacillus megaterium.", "content": "Cell-free extracts from sonically disrupted Bacillus megaterium ATCC 13368 hydroxylated a variety of 3-oxo-delta4-steroids in position 15beta in the presence of NADPH and O2. Ring A-reduced, aromatic and 3beta-hydroxy-delta5-steroids did not serve as substrates for the 15beta-hydroxylase system. Using ion exchange chromatography on DEAE-cellulose and gel filtration on Ultrogel ACA-54 it was possible to resolve the hydroxylase system into three proteins: a strictly NADPH-dependent FMN-containing (megaredoxin reductase), an iron-sulfur protein (megaredoxin), and cytochrome P-450 (P-450meg). The activity of the 15beta-hydroxylase system was fully reconstituted upon combination of these three proteins and addition of NADPH. Megaredoxin had an apparent sulfur to iron ration of 0.98 and showed g-signals at 1.90, 1.93, and 2.06 when analyzed by electron paramagnetic reso0 times and the preparation contained 1 to 2 nmol of cytochrome P-450 per mg of protein. This preparation of cytochrome P-450meg sedimented as a homogeneous zone on sucrose gradients with a sedimentation coefficient of 3.3 S and contained 0.94 nmol of heme per nmol of cytochrome P-450. The oxidized form of cytochrome P-450meg showed absolute absorption maxima at 416, 528, and 565 nm whereas the reduced form showed maxima at 411 and 542 nm. The following scheme is suggested for the electron transport in the 15beta-hydroxylase system in B. megaterium: NADPH leads to megaredoxin reductase leads to megaredoxin leads to cytochrome P-450meg.", "contents": "Characterization of a cytochrome P-450-dependent steroid hydroxylase system present in Bacillus megaterium. Cell-free extracts from sonically disrupted Bacillus megaterium ATCC 13368 hydroxylated a variety of 3-oxo-delta4-steroids in position 15beta in the presence of NADPH and O2. Ring A-reduced, aromatic and 3beta-hydroxy-delta5-steroids did not serve as substrates for the 15beta-hydroxylase system. Using ion exchange chromatography on DEAE-cellulose and gel filtration on Ultrogel ACA-54 it was possible to resolve the hydroxylase system into three proteins: a strictly NADPH-dependent FMN-containing (megaredoxin reductase), an iron-sulfur protein (megaredoxin), and cytochrome P-450 (P-450meg). The activity of the 15beta-hydroxylase system was fully reconstituted upon combination of these three proteins and addition of NADPH. Megaredoxin had an apparent sulfur to iron ration of 0.98 and showed g-signals at 1.90, 1.93, and 2.06 when analyzed by electron paramagnetic reso0 times and the preparation contained 1 to 2 nmol of cytochrome P-450 per mg of protein. This preparation of cytochrome P-450meg sedimented as a homogeneous zone on sucrose gradients with a sedimentation coefficient of 3.3 S and contained 0.94 nmol of heme per nmol of cytochrome P-450. The oxidized form of cytochrome P-450meg showed absolute absorption maxima at 416, 528, and 565 nm whereas the reduced form showed maxima at 411 and 542 nm. The following scheme is suggested for the electron transport in the 15beta-hydroxylase system in B. megaterium: NADPH leads to megaredoxin reductase leads to megaredoxin leads to cytochrome P-450meg."} {"id": "PMID:177423", "title": "Beta-Galactosidase messenger RNA made during recovery from inhibition of protein synthesis is not translated.", "content": "Bacteria that accumulate RNA in the course of inhibition of protein synthesis are impaired in their ability to synthesize beta-galactosidase during subsequent recovery. By contrast, constitutive enzyme synthesis in recovering cells is normal. Even though no beta-galactosidase is made during recovery from this inhibition, a substantial quantity of beta-galactosidase mRNA (as determined by DNA-RNA hybridization) is made. The beta-galactosidase mRNA made in vivo is functional in vitro. It is capable of directing the in vitro synthesis of a portion of the NH2-terminal beta-galactosidase molecule (in the alpha portion of the molecule). However, this protein is not made in vitro. It is concluded that the beta-galactosidase mRNA that is made during recovery from protein synthesis inhibition, although apparently at least partly normally transcribed in vivo and functional in vitro cannot be translated under these conditions in vivo.", "contents": "Beta-Galactosidase messenger RNA made during recovery from inhibition of protein synthesis is not translated. Bacteria that accumulate RNA in the course of inhibition of protein synthesis are impaired in their ability to synthesize beta-galactosidase during subsequent recovery. By contrast, constitutive enzyme synthesis in recovering cells is normal. Even though no beta-galactosidase is made during recovery from this inhibition, a substantial quantity of beta-galactosidase mRNA (as determined by DNA-RNA hybridization) is made. The beta-galactosidase mRNA made in vivo is functional in vitro. It is capable of directing the in vitro synthesis of a portion of the NH2-terminal beta-galactosidase molecule (in the alpha portion of the molecule). However, this protein is not made in vitro. It is concluded that the beta-galactosidase mRNA that is made during recovery from protein synthesis inhibition, although apparently at least partly normally transcribed in vivo and functional in vitro cannot be translated under these conditions in vivo."} {"id": "PMID:177424", "title": "Stoichiometry of carbon monoxide binding by cytochrome c oxidase.", "content": "The stoichiometry of carbon monoxide binding to beef heart cytochrome c oxidase has been reinvestigated both by titration of the reduced oxidase with CO and by measuring the amount of carboxyhemoglobin that is formed after adding oxyhemoglobin to a solution of the CO-enzyme complex. In the titration experiments the ratio of CO bounds to total heme a present was always less than 0.50 while in the experiments where oxyhemoglobin was added the results were variable and of lower accuracy. These observations do not agree with the recent conclusion of Volpe, J.A., O'Toole, M.C., and Caughey, W.S. (1975) Biochem. Biophys. Res. Commun. 62, 48-53 that CO is bound in a 1:1 ratio with heme a. An explanation for their results is suggested.", "contents": "Stoichiometry of carbon monoxide binding by cytochrome c oxidase. The stoichiometry of carbon monoxide binding to beef heart cytochrome c oxidase has been reinvestigated both by titration of the reduced oxidase with CO and by measuring the amount of carboxyhemoglobin that is formed after adding oxyhemoglobin to a solution of the CO-enzyme complex. In the titration experiments the ratio of CO bounds to total heme a present was always less than 0.50 while in the experiments where oxyhemoglobin was added the results were variable and of lower accuracy. These observations do not agree with the recent conclusion of Volpe, J.A., O'Toole, M.C., and Caughey, W.S. (1975) Biochem. Biophys. Res. Commun. 62, 48-53 that CO is bound in a 1:1 ratio with heme a. An explanation for their results is suggested."} {"id": "PMID:177425", "title": "The management of soft-tissue sarcomas of the extremities.", "content": "Of fifty-four patients with a soft-tissue sarcoma of an extremity, having a projected five-year survival rate of 62 per cent, forty-six treated by an \"adequate\" surgical procedure (either radical local resection or ablation at an appropriate level, depending on defined circumstances) had a local recurrence rate of 2 per cent. In the other eight patients, whose surgical procedures were not adequate for one reason or another, the local recurrence rate was 100 per cent. The combined recurrence rate after both the adequate and the inadequate procedures was 16.7 per cent. The recurrences were noted prior to thirty months post-operatively and the metastases, prior to sixty months. Histogenesis of the sarcoma, one or more recurrences after previous operations, and treatment by an immediate definitive procedure at the time of biopsy and diagnosis by frozen section had no significant relationship to the rates of local recurrence or metastasis. Adequate radical local resection controlled these sarcomas as well as ablative surgery in terms of local recurrence and metastasis. The significant factors affecting local recurrence that were identified in this study were the location of the sarcoma and the adequacy of the surgical procedure.", "contents": "The management of soft-tissue sarcomas of the extremities. Of fifty-four patients with a soft-tissue sarcoma of an extremity, having a projected five-year survival rate of 62 per cent, forty-six treated by an \"adequate\" surgical procedure (either radical local resection or ablation at an appropriate level, depending on defined circumstances) had a local recurrence rate of 2 per cent. In the other eight patients, whose surgical procedures were not adequate for one reason or another, the local recurrence rate was 100 per cent. The combined recurrence rate after both the adequate and the inadequate procedures was 16.7 per cent. The recurrences were noted prior to thirty months post-operatively and the metastases, prior to sixty months. Histogenesis of the sarcoma, one or more recurrences after previous operations, and treatment by an immediate definitive procedure at the time of biopsy and diagnosis by frozen section had no significant relationship to the rates of local recurrence or metastasis. Adequate radical local resection controlled these sarcomas as well as ablative surgery in terms of local recurrence and metastasis. The significant factors affecting local recurrence that were identified in this study were the location of the sarcoma and the adequacy of the surgical procedure."} {"id": "PMID:177426", "title": "Exfoliative cytology interpretation of synovial fluid in joint disease.", "content": "Criteria for the specific diagnoses of the several arthritides, on the basis of exfoliative cytology examination of fluids aspirated from diseased joints, were derived from examinations of 126 specimens of synovial fluid. They were screened cytologically and wholly on the basis of the cytological findings were classified into seven groups: rheumatoid arthritis, osteoarthritis, traumatic arthritis, gouty arthritis, Reiter's syndrome, pigmented villonodualr synovitis, and septic arthritis. The cytological features of each group appeared relatively constant and reproducible. Subsequent comparison of the clinical and cytological diagnoses showed excellent correlation.", "contents": "Exfoliative cytology interpretation of synovial fluid in joint disease. Criteria for the specific diagnoses of the several arthritides, on the basis of exfoliative cytology examination of fluids aspirated from diseased joints, were derived from examinations of 126 specimens of synovial fluid. They were screened cytologically and wholly on the basis of the cytological findings were classified into seven groups: rheumatoid arthritis, osteoarthritis, traumatic arthritis, gouty arthritis, Reiter's syndrome, pigmented villonodualr synovitis, and septic arthritis. The cytological features of each group appeared relatively constant and reproducible. Subsequent comparison of the clinical and cytological diagnoses showed excellent correlation."} {"id": "PMID:177428", "title": "The Budd-Chiari syndrome: angiography and its complications.", "content": "Four patients with the Budd-Chiari syndrome are presented. Hepatic venography and inferior vena cavography confirmed the diagnosis in these patients. Angiography was used to evaluate the liver and the superior mesenteric and portal venous drainage. Contrast medium complications, ranging from nausea to renal shut-down and death, were encountered in three of these patients, an unusually high number of angiographic complications. The role of angiography in the Budd-Chiari syndrome is assessed.", "contents": "The Budd-Chiari syndrome: angiography and its complications. Four patients with the Budd-Chiari syndrome are presented. Hepatic venography and inferior vena cavography confirmed the diagnosis in these patients. Angiography was used to evaluate the liver and the superior mesenteric and portal venous drainage. Contrast medium complications, ranging from nausea to renal shut-down and death, were encountered in three of these patients, an unusually high number of angiographic complications. The role of angiography in the Budd-Chiari syndrome is assessed."} {"id": "PMID:177429", "title": "Membrane behavior of exocytic vesicles. II. Fate of the trichocyst membranes in Paramecium after induced trichocyst discharge.", "content": "A specific exocytic process, the discharge of spindle trichocyts of Paramecium caudatum, was examined by means of the electron microscope. This exocytosis is induced by an electric shock simultaneously in nearly all of the trichocysts (ca. 6,000-8,000) of a single cell. Single paramecia were subjected to the shock and then fixed at defined times after the shock so that the temporal sequence of the pattern of changes of the trichocyst membranes after exocytosis could be studied. The trichocyst vacuoles fuse with the plasma membrane only for the length of time required for expulsion to take place. After exocytosis, the membrane of the vacuole does not become incorporated into the plasma membrane; rather, the collapsed vacuole is pinched off and breaks up within the cytoplasm. The membrane vesiculates into small units which can no longer be distinguished from vesicles of the same dimensions that exist normally within the cell's cytoplasm. The entire process is completed within 5-10 min. These results differ from the incorporation of mucocyst membranes into the plasma membrane as proposed for Tetrahymena.", "contents": "Membrane behavior of exocytic vesicles. II. Fate of the trichocyst membranes in Paramecium after induced trichocyst discharge. A specific exocytic process, the discharge of spindle trichocyts of Paramecium caudatum, was examined by means of the electron microscope. This exocytosis is induced by an electric shock simultaneously in nearly all of the trichocysts (ca. 6,000-8,000) of a single cell. Single paramecia were subjected to the shock and then fixed at defined times after the shock so that the temporal sequence of the pattern of changes of the trichocyst membranes after exocytosis could be studied. The trichocyst vacuoles fuse with the plasma membrane only for the length of time required for expulsion to take place. After exocytosis, the membrane of the vacuole does not become incorporated into the plasma membrane; rather, the collapsed vacuole is pinched off and breaks up within the cytoplasm. The membrane vesiculates into small units which can no longer be distinguished from vesicles of the same dimensions that exist normally within the cell's cytoplasm. The entire process is completed within 5-10 min. These results differ from the incorporation of mucocyst membranes into the plasma membrane as proposed for Tetrahymena."} {"id": "PMID:177430", "title": "Subcellular localization of B apoprotein of plasma lipoproteins in rat liver.", "content": "Multispecific antigen-binding fragments (Fab) from rabbit antisera against rat very low density lipoproteins (VLDL) and Fab against rat low density lipoproteins that were monospecific for the B apoprotein were conjugated to horseradish peroxidase. Conjugates were incubated with 6-mum frozen sections from fresh and perfusion-fixed livers and with tissue chopper sections (40 mum thick) from perfusion-fixed livers. In the light microscope, specific reaction product was present in all hepatocytes of experimental sections as intense brown to black spots whose locations corresponded to the distribution of the Golgi apparatus: along the bile canaliculi, near the nuclei, and between the nuclei and bile canaliculi. Perfusion fixation with formaldehyde produced satisfactory ultrastructural preservation with retention of lipoprotein antigenic determinants. In the electron microscope, patches of cisternae and ribosomes of the rough endoplasmic reticulum (ER) and particularly its smooth-surfaced ends, vesicles located between the rough ER and the Golgi apparatus, the Golgi apparatus and its secretory vesicles and VLDL particles in the space of Disse all bore reaction product. The tubules and vesicles of typical hepatocyte smooth ER did not contain reaction product, nor did the osmiophilic particles contained therin. The localization obtained in this study together with other evidence suggests a sequence for the biosynthesis of VLDL that differs in some respects from that proposed by others: (a) the triglyceride-rich particle originates in smooth ER where triglycerides are synthesized; (b) at the junction of the smooth and rough ER the particle receives apoproteins synthesized in the rough ER; (c) specialized tubules transport the particle, now a nascent lipoprotein, to the Golgi apparatus where concentration occurs in secretory vesicles; (d) secretory vesicles move to the sinusoidal surface where the particles are secreted into the space of Disse by fusion of the vesicular membrane with the plasma membrane of the hepatocyte.", "contents": "Subcellular localization of B apoprotein of plasma lipoproteins in rat liver. Multispecific antigen-binding fragments (Fab) from rabbit antisera against rat very low density lipoproteins (VLDL) and Fab against rat low density lipoproteins that were monospecific for the B apoprotein were conjugated to horseradish peroxidase. Conjugates were incubated with 6-mum frozen sections from fresh and perfusion-fixed livers and with tissue chopper sections (40 mum thick) from perfusion-fixed livers. In the light microscope, specific reaction product was present in all hepatocytes of experimental sections as intense brown to black spots whose locations corresponded to the distribution of the Golgi apparatus: along the bile canaliculi, near the nuclei, and between the nuclei and bile canaliculi. Perfusion fixation with formaldehyde produced satisfactory ultrastructural preservation with retention of lipoprotein antigenic determinants. In the electron microscope, patches of cisternae and ribosomes of the rough endoplasmic reticulum (ER) and particularly its smooth-surfaced ends, vesicles located between the rough ER and the Golgi apparatus, the Golgi apparatus and its secretory vesicles and VLDL particles in the space of Disse all bore reaction product. The tubules and vesicles of typical hepatocyte smooth ER did not contain reaction product, nor did the osmiophilic particles contained therin. The localization obtained in this study together with other evidence suggests a sequence for the biosynthesis of VLDL that differs in some respects from that proposed by others: (a) the triglyceride-rich particle originates in smooth ER where triglycerides are synthesized; (b) at the junction of the smooth and rough ER the particle receives apoproteins synthesized in the rough ER; (c) specialized tubules transport the particle, now a nascent lipoprotein, to the Golgi apparatus where concentration occurs in secretory vesicles; (d) secretory vesicles move to the sinusoidal surface where the particles are secreted into the space of Disse by fusion of the vesicular membrane with the plasma membrane of the hepatocyte."} {"id": "PMID:177431", "title": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. I. Ultrastructural analysis of organelles.", "content": "Electron microscope studies have been made on the fine structure of the colorless biflagellate, Polytoma obtusum, with main emphasis on the structural organization of the mitochondria and the leucoplast. Both organelles have been demonstrated to contain DNA aggregates as well as ribosomal particles within their matrix material. Reconstructions from serial showed that (a) the mitochondria were highly convoluted and irregular in shape and size, and (b) the leucoplast was a single cup-shaped entity, with large starch grains, localized at the posterior end, and multiple sites of DNA aggregates. The starch-containing compartments appeared to be interconnected by narrow tubular or sheetlike bridges. Cytoplasmic invaginations into the plastid, often containing mitochondria, were of frequent occurrence, and membranes of mitochondria and the leucoplast appeared to be closely apposed. Membranes elements, both sheetlike and vesicular, were also present in the matrix. The Polytoma leucoplast was, in certain respects, morphologically similar to the plastids of various photosynthetic mutants of Chlamydomonas, most of which show Menedelian segregation. It is suggested that Polytoma arose from a Chlamydomonas-like ancestor, possibly through combined mutational processess of both chloroplast and nuclear genomes. Since Polytoma leucoplasts contain both DNA and ribosomal particles, it is probable that these organelles still possess semiautonomy and limited ability for protein synthesis.", "contents": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. I. Ultrastructural analysis of organelles. Electron microscope studies have been made on the fine structure of the colorless biflagellate, Polytoma obtusum, with main emphasis on the structural organization of the mitochondria and the leucoplast. Both organelles have been demonstrated to contain DNA aggregates as well as ribosomal particles within their matrix material. Reconstructions from serial showed that (a) the mitochondria were highly convoluted and irregular in shape and size, and (b) the leucoplast was a single cup-shaped entity, with large starch grains, localized at the posterior end, and multiple sites of DNA aggregates. The starch-containing compartments appeared to be interconnected by narrow tubular or sheetlike bridges. Cytoplasmic invaginations into the plastid, often containing mitochondria, were of frequent occurrence, and membranes of mitochondria and the leucoplast appeared to be closely apposed. Membranes elements, both sheetlike and vesicular, were also present in the matrix. The Polytoma leucoplast was, in certain respects, morphologically similar to the plastids of various photosynthetic mutants of Chlamydomonas, most of which show Menedelian segregation. It is suggested that Polytoma arose from a Chlamydomonas-like ancestor, possibly through combined mutational processess of both chloroplast and nuclear genomes. Since Polytoma leucoplasts contain both DNA and ribosomal particles, it is probable that these organelles still possess semiautonomy and limited ability for protein synthesis."} {"id": "PMID:177432", "title": "Nucleotidase activity in regenerating liver and in clonal strains of hepatoma and pituitary cells in culture.", "content": "A nucleotidase of the combined 3'- and 5'-type (nucleotide phosphohydrolase, E.C.3.1.3.31) was present in the cytosol of regenerating rat liver cells, and of rat hepatoma and pituitary cells in culture. The enzyme activity per milligram of cell protein was very similar in regenerating liver and in three of the different cell types. The hepatoma cell strain which showed the slowest growth rate had a three-fold higher basal enzyme activity. After the first days of regenerative growth in rat liver and during early plateau phase of cell growth, there was a 50-120% increase in specific enzyme activity. In the hepatoma cells, the enzyme activities were also compared to the cellular content and synthesis of RNA and DNA. The increase in enzyme activity occurred concomitantly with a reduced incorporation of 3H-thymidine into DNA. The possible physiological role of this nucleotidase in nucleic acid and nucleotide metabolism is discussed.", "contents": "Nucleotidase activity in regenerating liver and in clonal strains of hepatoma and pituitary cells in culture. A nucleotidase of the combined 3'- and 5'-type (nucleotide phosphohydrolase, E.C.3.1.3.31) was present in the cytosol of regenerating rat liver cells, and of rat hepatoma and pituitary cells in culture. The enzyme activity per milligram of cell protein was very similar in regenerating liver and in three of the different cell types. The hepatoma cell strain which showed the slowest growth rate had a three-fold higher basal enzyme activity. After the first days of regenerative growth in rat liver and during early plateau phase of cell growth, there was a 50-120% increase in specific enzyme activity. In the hepatoma cells, the enzyme activities were also compared to the cellular content and synthesis of RNA and DNA. The increase in enzyme activity occurred concomitantly with a reduced incorporation of 3H-thymidine into DNA. The possible physiological role of this nucleotidase in nucleic acid and nucleotide metabolism is discussed."} {"id": "PMID:177433", "title": "Induction by short-chain fatty acids of alkaline phosphatase activity in cultured mammalian cells.", "content": "Short-chain fatty acids, such as propionic, n-butyric, n-butyric, n-valeric, isovaleric, n-caproic, and n-caprylic acids, induce alkaline phosphatase activity in cultured mammalian cells. Long-chain fatty acids have no similar effects. With B-6 cells (mouse X Chinese hamster cell hybrids), n-butyrate at 2 to 5 mM exhibits the greatest activity. Induction begins exponentially about 24 hours after addition of the fatty acid and continues over 48 hours. Studies on the inducing activity-structure relationship revealed the necessity of a carboxyl and an ethyl or longer alkyl group. n-Butyrate shows a marked synergistic action of induction when added along with other types of inducers: adenosine 3':5'-cyclic monophosphate (cAMP) or 5-bromodeoxyuridine (BrdU). Treatment of other cell lines with either n-buryrate, cAMP, or BrdU revealed a cell-type specific response pattern of alkaline phosphatase. The biological significance of this effect of short-chain fatty acids is discussed.", "contents": "Induction by short-chain fatty acids of alkaline phosphatase activity in cultured mammalian cells. Short-chain fatty acids, such as propionic, n-butyric, n-butyric, n-valeric, isovaleric, n-caproic, and n-caprylic acids, induce alkaline phosphatase activity in cultured mammalian cells. Long-chain fatty acids have no similar effects. With B-6 cells (mouse X Chinese hamster cell hybrids), n-butyrate at 2 to 5 mM exhibits the greatest activity. Induction begins exponentially about 24 hours after addition of the fatty acid and continues over 48 hours. Studies on the inducing activity-structure relationship revealed the necessity of a carboxyl and an ethyl or longer alkyl group. n-Butyrate shows a marked synergistic action of induction when added along with other types of inducers: adenosine 3':5'-cyclic monophosphate (cAMP) or 5-bromodeoxyuridine (BrdU). Treatment of other cell lines with either n-buryrate, cAMP, or BrdU revealed a cell-type specific response pattern of alkaline phosphatase. The biological significance of this effect of short-chain fatty acids is discussed."} {"id": "PMID:177434", "title": "SV40 transformation of mouse brain cells: critical role of gene A in maintenance of the transformed phenotype.", "content": "Brain cells derived from the NIH Swiss mouse strain have been established in tissue culture. Astrocytic neuroglial cells, identified by morphology and staining properties, predominate. The brain cell culture was successfully transformed with SV40 wild type virus and with a representative early (A239) and late (C219) mutant. When subjected to growth analysis the A239 transformant displayed selective loss of six characteristics of the transformed phenotype at the restrictive temperature (40.5 degrees C): doubling time, saturation density, ability to grow in low serum, efficiency of growth on plastic and on normal brain cell layers, and cloning in soft agar. Temperature shift experiment demonstrated the reversibility of the differences in saturation density. T-antigen was expressed at both temperatures. Alteration in uptake of 2-deoxyglucose was not a characteristic of the transformed phenotype. The cell lines may be utility in brain culture work and in studies on the mechanism of SV40 transformation.", "contents": "SV40 transformation of mouse brain cells: critical role of gene A in maintenance of the transformed phenotype. Brain cells derived from the NIH Swiss mouse strain have been established in tissue culture. Astrocytic neuroglial cells, identified by morphology and staining properties, predominate. The brain cell culture was successfully transformed with SV40 wild type virus and with a representative early (A239) and late (C219) mutant. When subjected to growth analysis the A239 transformant displayed selective loss of six characteristics of the transformed phenotype at the restrictive temperature (40.5 degrees C): doubling time, saturation density, ability to grow in low serum, efficiency of growth on plastic and on normal brain cell layers, and cloning in soft agar. Temperature shift experiment demonstrated the reversibility of the differences in saturation density. T-antigen was expressed at both temperatures. Alteration in uptake of 2-deoxyglucose was not a characteristic of the transformed phenotype. The cell lines may be utility in brain culture work and in studies on the mechanism of SV40 transformation."} {"id": "PMID:177435", "title": "Separation of vitamin D metabolites and their analogues by high-pressure liquid chromatography.", "content": "The separation of vitamin D3 metabolites and their analogues by high-pressure liquid chromatography was investigated using a Zorbax SIL column. Each metabolite can be separated effectively with a solvent consisting of 2% methanol-methylene chloride or gradient elution from 0.02% to 6% methanol-methylene chloride. The C-24 epimers of 1alpha, 24-dihydroxy- and 1alpha,24,25-trihydroxy-vitamin D3 are resolved as their free forms, while the epimers of 24-hydroxy- and 24,25-dihydroxy-vitamin D3 can be separated as their trimethylsilyl derivatives.", "contents": "Separation of vitamin D metabolites and their analogues by high-pressure liquid chromatography. The separation of vitamin D3 metabolites and their analogues by high-pressure liquid chromatography was investigated using a Zorbax SIL column. Each metabolite can be separated effectively with a solvent consisting of 2% methanol-methylene chloride or gradient elution from 0.02% to 6% methanol-methylene chloride. The C-24 epimers of 1alpha, 24-dihydroxy- and 1alpha,24,25-trihydroxy-vitamin D3 are resolved as their free forms, while the epimers of 24-hydroxy- and 24,25-dihydroxy-vitamin D3 can be separated as their trimethylsilyl derivatives."} {"id": "PMID:177436", "title": "Study on the efficiency of support-coated open-tubular columns for steroid analysis.", "content": "Glass support-coated open-tubular columns for the analysis of steroids in biological samples were prepared with varous support materials. The reproducibility of the procedure of preparing the column was investigated and some fundamental chromatographic properties were studied.", "contents": "Study on the efficiency of support-coated open-tubular columns for steroid analysis. Glass support-coated open-tubular columns for the analysis of steroids in biological samples were prepared with varous support materials. The reproducibility of the procedure of preparing the column was investigated and some fundamental chromatographic properties were studied."} {"id": "PMID:177437", "title": "Increased plasma protein binding and lower metabolic clearance rate of aldosterone in plasma of low cortisol concentration.", "content": "During ACTH or cortisol infusion in ten recumbent normal men taking dexamethasone, the metabolic clearance rate of aldosterone increased by 50% as plasma cortisol was raised from low (2 mug/dl) to high concentration (50 mug/dl). Since splanchnic blood flow did not change, a greater efficiency of removal of aldosterone must have occurred, by means of displacement of aldosterone from high-affinity sites on plasma protein. At 37 C, equilibrium dialysis of low-cortisol plasma showed one-third of plasma aldosterone bound to albumin, and 24 to 28% bound to higher-affinity sites on other protein. As plasma cortisol increased, a progressively smaller fraction was tightly bound, approaching zero as transcortin was saturated with cortisol. The addition of large amounts of aldosterone to low-cortisol plasma displaced 14C-cortisol from transcortin binding sites. The results support earlier evidence that a significant fraction of plasma aldosterone is bound to transcortin, from which it is readily displaced by cortisol, resulting in an increased metabolic clearance rate of aldosterone by making a larger fraction available for removal from plasma.", "contents": "Increased plasma protein binding and lower metabolic clearance rate of aldosterone in plasma of low cortisol concentration. During ACTH or cortisol infusion in ten recumbent normal men taking dexamethasone, the metabolic clearance rate of aldosterone increased by 50% as plasma cortisol was raised from low (2 mug/dl) to high concentration (50 mug/dl). Since splanchnic blood flow did not change, a greater efficiency of removal of aldosterone must have occurred, by means of displacement of aldosterone from high-affinity sites on plasma protein. At 37 C, equilibrium dialysis of low-cortisol plasma showed one-third of plasma aldosterone bound to albumin, and 24 to 28% bound to higher-affinity sites on other protein. As plasma cortisol increased, a progressively smaller fraction was tightly bound, approaching zero as transcortin was saturated with cortisol. The addition of large amounts of aldosterone to low-cortisol plasma displaced 14C-cortisol from transcortin binding sites. The results support earlier evidence that a significant fraction of plasma aldosterone is bound to transcortin, from which it is readily displaced by cortisol, resulting in an increased metabolic clearance rate of aldosterone by making a larger fraction available for removal from plasma."} {"id": "PMID:177438", "title": "The hormonal activity of the postmenopausal ovary.", "content": "The origin of plasma sex hormones in postmenopausal women was studied by determining plasma levels under basal conditions, after ACTH stimulation, and after dexamethasone suppression, as well as after hCG stimulation. Values obtained in postmenopausal women were compared with values observed during the follicular phase of the cycle in young women on the one hand, and with values in ovariectomized women of postmenopausal age on the other hand. All sex steroid levels studied with the exception of estrone, were significantly lower in postmenopausal women than in young women during the early follicular phase of the cycle. In ovariectomized women only androgen levels (testosterone, androstenedione, dihydrotestosterone, and to a lesser extent dehydroepiandrosterone,) were lower than in normal postmenopausal women, estrogen, 17 hydroxyprogesterone, and progesterone levels being similar. ACTH increased all plasma steroid levels except estradiol, whereas after dexamethasone, all sex hormone levels were significantly decreased. hCG stimulation finally caused an increase of borderline statistical significance in testosterone, dehydroepiandrosterone, and 17-hydroxyprogesterone levels. We have concluded from this study that the adrenal cortex is almost the exclusive source of plasma estradiol, estrone, progesterone, and 17OH progesterone and the most important source of plasma dehydroepiandrosterone; that the postmenopausal ovary appears to be responsible for about 50% of plasma testosterone and 30% of androstenedione levels; and that hCG stimulation with 5000 IU daily for 3 days, hardly influences steroid secretion by postmenopausal ovaries.", "contents": "The hormonal activity of the postmenopausal ovary. The origin of plasma sex hormones in postmenopausal women was studied by determining plasma levels under basal conditions, after ACTH stimulation, and after dexamethasone suppression, as well as after hCG stimulation. Values obtained in postmenopausal women were compared with values observed during the follicular phase of the cycle in young women on the one hand, and with values in ovariectomized women of postmenopausal age on the other hand. All sex steroid levels studied with the exception of estrone, were significantly lower in postmenopausal women than in young women during the early follicular phase of the cycle. In ovariectomized women only androgen levels (testosterone, androstenedione, dihydrotestosterone, and to a lesser extent dehydroepiandrosterone,) were lower than in normal postmenopausal women, estrogen, 17 hydroxyprogesterone, and progesterone levels being similar. ACTH increased all plasma steroid levels except estradiol, whereas after dexamethasone, all sex hormone levels were significantly decreased. hCG stimulation finally caused an increase of borderline statistical significance in testosterone, dehydroepiandrosterone, and 17-hydroxyprogesterone levels. We have concluded from this study that the adrenal cortex is almost the exclusive source of plasma estradiol, estrone, progesterone, and 17OH progesterone and the most important source of plasma dehydroepiandrosterone; that the postmenopausal ovary appears to be responsible for about 50% of plasma testosterone and 30% of androstenedione levels; and that hCG stimulation with 5000 IU daily for 3 days, hardly influences steroid secretion by postmenopausal ovaries."} {"id": "PMID:177439", "title": "Pituitary-thyroid function in trophoblastic disease.", "content": "Pituitary-thyroid function was assessed in 12 patients with trophoblastic disease (4 hydatidiform mole, 3 invasive mole, and 5 choriocarcinoma). Thyroid-stimulating activity was detectable, by means of the McKenzie bioassay, in 6 patients (Group 1) but not in the other 6 patients (Group 2). In Group 1 serum thyrotropin (TSH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH), while in Group 2 basal TSH was detectable in half of the patients and responded to TRH in all cases. Serum concentrations of total thyroxine (T4) (18.7 +/- 2.0 mug/100 ml, mean +/- SE), free T4 (4.9 +/- 0.04 ng/100 ml), total triiodothyronine (T3) (352 +/- 72 ng/100 ml), and free T3 (0.57 +/- 0.11 ng/100 ml) in Group 1 were statistically greater than those in Group 2 (total T4, 9.2 +/- 1.0 mug/100 ml, free T4, 2.0 +/- 0.2 ng/100 ml; total T3 156 +/- 20 ng/100 ml, and free T3 0.23 +/- 0.03 ng/100 ml). Free T4 and T3 fractions were within normal limits in both groups. After treatment of 5 patients in Group 1, the thyroid stimulating activity determined by bioassay dropped to undetectable levels, the serum concentrations of thyroid hormones decreased to normal limits, and TSH response to TRH became positive. These findings indicate that an abnormal thyroid stimulator, derived from the trophoblastic tissue, stimulated the thyroid hormone secretion from the thyroid gland and in turn suppressed TSH response to TRH in some patients with trophoblastic disease.", "contents": "Pituitary-thyroid function in trophoblastic disease. Pituitary-thyroid function was assessed in 12 patients with trophoblastic disease (4 hydatidiform mole, 3 invasive mole, and 5 choriocarcinoma). Thyroid-stimulating activity was detectable, by means of the McKenzie bioassay, in 6 patients (Group 1) but not in the other 6 patients (Group 2). In Group 1 serum thyrotropin (TSH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH), while in Group 2 basal TSH was detectable in half of the patients and responded to TRH in all cases. Serum concentrations of total thyroxine (T4) (18.7 +/- 2.0 mug/100 ml, mean +/- SE), free T4 (4.9 +/- 0.04 ng/100 ml), total triiodothyronine (T3) (352 +/- 72 ng/100 ml), and free T3 (0.57 +/- 0.11 ng/100 ml) in Group 1 were statistically greater than those in Group 2 (total T4, 9.2 +/- 1.0 mug/100 ml, free T4, 2.0 +/- 0.2 ng/100 ml; total T3 156 +/- 20 ng/100 ml, and free T3 0.23 +/- 0.03 ng/100 ml). Free T4 and T3 fractions were within normal limits in both groups. After treatment of 5 patients in Group 1, the thyroid stimulating activity determined by bioassay dropped to undetectable levels, the serum concentrations of thyroid hormones decreased to normal limits, and TSH response to TRH became positive. These findings indicate that an abnormal thyroid stimulator, derived from the trophoblastic tissue, stimulated the thyroid hormone secretion from the thyroid gland and in turn suppressed TSH response to TRH in some patients with trophoblastic disease."} {"id": "PMID:177440", "title": "Acute administration of 25-hydroxycholecalciferol in man.", "content": "Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 mug per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 mug/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline to total serum 25-hydroxycholecalciferol was slow (t 1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration.", "contents": "Acute administration of 25-hydroxycholecalciferol in man. Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 mug per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 mug/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline to total serum 25-hydroxycholecalciferol was slow (t 1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration."} {"id": "PMID:177441", "title": "Modification of adrenal function by the anti-serotonin agent cyproheptadine.", "content": "The effect of the serotonin antagonist, cyproheptadine (Cypro), on metyrapone-induced stimulation of the pituitary-adrenal axis was evaluated in nine normal subjects. The subjects underwent standard oral metyrapone tests (750 mg every four h, for six doses) while taking no medications and while receiving oral Cypro (4 mg every six h). Cypro administration caused a significant reduction in: 1) baseline 17-hydroxycorticosteroid (17-OH) excretion (-31 +/- 7.2%), 2) the increase above baseline in 24 h 17-OH excretion on the day after metyrapone (-32 +/- 4.9%), 3) serum 11-deoxycortisol concentrations 8 h (-45 +/- 5.5%) and 24 h (-18 +/- 3.6%) after the first dose of metyrapone, and 4) plasma ACTH concentration 8 h (-32 +/- 8.2%) and 24 h (-22 +/- 8.0%) after the first dose of metyrapone. When compared with the control test, Cypro administration did not alter: 1) baseline 17-ketosteroid secretion, 2) the fall in serum cortisol concentration while taking metyrapone, 3) the serum free metyrapone concentration, 4) cortisol metabolism, 5) the adrenal response to ACTH, and 6) assay methods for measurement of serum and urinary corticosteroids. Our data suggest that Cypro can reduce pituitary-adrenal responsiveness by reducing plasma ACTH concentrations. If Cypro acts as a serotonin antagonist, our data lends support to the idea that serotoninergic mechanisms are important in the control of pituitary ACTH secretion in normal human subjects.", "contents": "Modification of adrenal function by the anti-serotonin agent cyproheptadine. The effect of the serotonin antagonist, cyproheptadine (Cypro), on metyrapone-induced stimulation of the pituitary-adrenal axis was evaluated in nine normal subjects. The subjects underwent standard oral metyrapone tests (750 mg every four h, for six doses) while taking no medications and while receiving oral Cypro (4 mg every six h). Cypro administration caused a significant reduction in: 1) baseline 17-hydroxycorticosteroid (17-OH) excretion (-31 +/- 7.2%), 2) the increase above baseline in 24 h 17-OH excretion on the day after metyrapone (-32 +/- 4.9%), 3) serum 11-deoxycortisol concentrations 8 h (-45 +/- 5.5%) and 24 h (-18 +/- 3.6%) after the first dose of metyrapone, and 4) plasma ACTH concentration 8 h (-32 +/- 8.2%) and 24 h (-22 +/- 8.0%) after the first dose of metyrapone. When compared with the control test, Cypro administration did not alter: 1) baseline 17-ketosteroid secretion, 2) the fall in serum cortisol concentration while taking metyrapone, 3) the serum free metyrapone concentration, 4) cortisol metabolism, 5) the adrenal response to ACTH, and 6) assay methods for measurement of serum and urinary corticosteroids. Our data suggest that Cypro can reduce pituitary-adrenal responsiveness by reducing plasma ACTH concentrations. If Cypro acts as a serotonin antagonist, our data lends support to the idea that serotoninergic mechanisms are important in the control of pituitary ACTH secretion in normal human subjects."} {"id": "PMID:177442", "title": "The effect of administered ACTH on aldosterone metabolism and secretion.", "content": "To determine better the overall regulation of aldosterone by ACTH, the effect of administered ACTH on the aldosterone metabolic clearance rate (MCR), the excretion rates of tetrahydroaldosterone (THAldo), and the acid-labile conjugate (ALC) of aldosterone were studied in healthy male volunteers on a sodium intake in excess of 200 mEq/day. In 7 subjects, the aldosterone MCR increased significantly on the third day of ACTH treatment, as did the excretion of THAldo, but there was a decrease in the excretion of the ALC. One subject receiving ACTH for 6 days showed a steady increase in the aldosterone MCR on days 3 and 6 of treatment. In 2 of 3 subjects receiving ACTH treatment for 3-4 days, plasma aldosterone levels and plasma renin activity showed little change, whereas in 1 subject, both plasma aldosterone and plasma renin activity became suppressed. During ACTH administration there was a sustained increase in the excretion of THAldo, a metabolite formed in the liver, (in contrast to a decreasing excretion of the ALC which is made principally in the kidneys) which suggests that the increased aldosterone metabolism in response to ACTH occurred in the liver. Measurements made of the excretion of THAldo show that the ACTH stimulatory effect on aldosterone secretion may not be as transient as previously reported.", "contents": "The effect of administered ACTH on aldosterone metabolism and secretion. To determine better the overall regulation of aldosterone by ACTH, the effect of administered ACTH on the aldosterone metabolic clearance rate (MCR), the excretion rates of tetrahydroaldosterone (THAldo), and the acid-labile conjugate (ALC) of aldosterone were studied in healthy male volunteers on a sodium intake in excess of 200 mEq/day. In 7 subjects, the aldosterone MCR increased significantly on the third day of ACTH treatment, as did the excretion of THAldo, but there was a decrease in the excretion of the ALC. One subject receiving ACTH for 6 days showed a steady increase in the aldosterone MCR on days 3 and 6 of treatment. In 2 of 3 subjects receiving ACTH treatment for 3-4 days, plasma aldosterone levels and plasma renin activity showed little change, whereas in 1 subject, both plasma aldosterone and plasma renin activity became suppressed. During ACTH administration there was a sustained increase in the excretion of THAldo, a metabolite formed in the liver, (in contrast to a decreasing excretion of the ALC which is made principally in the kidneys) which suggests that the increased aldosterone metabolism in response to ACTH occurred in the liver. Measurements made of the excretion of THAldo show that the ACTH stimulatory effect on aldosterone secretion may not be as transient as previously reported."} {"id": "PMID:177443", "title": "Presence of TSH receptor in thyroid neoplasms.", "content": "The nature of the TSH receptor in adenoma and carcinoma of the thyroid gland was studied using a radioreceptor assay technique. A membrane fraction of tissue homogenate was obtained by discontinuous sucrose gradient ultracentrifugation, and 125I-TSH, labelled by a lactoperoxidase method, was purified with a receptor adsorption method. Both the capacities and the association constants of high affinity receptors (4 x 10(9) M-1) and of low affinity receptors (0.073 x 10(9) M-1) observed in the normal thyroid were almost identical to those of the thyroid of Graves' disease and those of thyroid adenoma. Although the two papillary carcinomas examined were found to have two kinds of TSH receptors, one of the carcinomas showed decreased association constants for both high affinity and low affinity receptors.", "contents": "Presence of TSH receptor in thyroid neoplasms. The nature of the TSH receptor in adenoma and carcinoma of the thyroid gland was studied using a radioreceptor assay technique. A membrane fraction of tissue homogenate was obtained by discontinuous sucrose gradient ultracentrifugation, and 125I-TSH, labelled by a lactoperoxidase method, was purified with a receptor adsorption method. Both the capacities and the association constants of high affinity receptors (4 x 10(9) M-1) and of low affinity receptors (0.073 x 10(9) M-1) observed in the normal thyroid were almost identical to those of the thyroid of Graves' disease and those of thyroid adenoma. Although the two papillary carcinomas examined were found to have two kinds of TSH receptors, one of the carcinomas showed decreased association constants for both high affinity and low affinity receptors."} {"id": "PMID:177444", "title": "Radioreceptor assay for insulin.", "content": "A sensitive and simple radioreceptor assay (RRA) capable of detecting 10 muU/ml of serum insulin has been developed using the crude membrane fraction of guinea pig kidney and 125I-porcine insulin. Using this assay system, serum insulin during 100 g oral glucose tolerance tests in six males including one obese man was measured. The mean concentration of serum insulin increased from 19 muU/ml during fasting to maximum of 90 muU/ml after 60 min of glucose load and then gradually declined to 38 muU/ml by 180 min. The values obtained by the present RRA agreed well with immunoreactive insulin (IRI).", "contents": "Radioreceptor assay for insulin. A sensitive and simple radioreceptor assay (RRA) capable of detecting 10 muU/ml of serum insulin has been developed using the crude membrane fraction of guinea pig kidney and 125I-porcine insulin. Using this assay system, serum insulin during 100 g oral glucose tolerance tests in six males including one obese man was measured. The mean concentration of serum insulin increased from 19 muU/ml during fasting to maximum of 90 muU/ml after 60 min of glucose load and then gradually declined to 38 muU/ml by 180 min. The values obtained by the present RRA agreed well with immunoreactive insulin (IRI)."} {"id": "PMID:177445", "title": "Receptor-active growth hormone in Laron dwarfism.", "content": "The hepatic radioreceptor assay for hGH has been applied to the detection of hGH in the sera of patients with high growth hormone dwarfism (Laron dwarfism). Substantial quantities of receptor-active hGH were found in the sera of all 7 patients studied. In one patient, arginine infusion elicited a prompt increase in both immunoactive and receptor-active hGH. These observations suggest that circulating hGH in Laron dwarfism is biologically active and support the concept that the disease may be caused by a generalized defect in hGH receptors.", "contents": "Receptor-active growth hormone in Laron dwarfism. The hepatic radioreceptor assay for hGH has been applied to the detection of hGH in the sera of patients with high growth hormone dwarfism (Laron dwarfism). Substantial quantities of receptor-active hGH were found in the sera of all 7 patients studied. In one patient, arginine infusion elicited a prompt increase in both immunoactive and receptor-active hGH. These observations suggest that circulating hGH in Laron dwarfism is biologically active and support the concept that the disease may be caused by a generalized defect in hGH receptors."} {"id": "PMID:177446", "title": "Progesterone binding by normal and abnormal human endometrium.", "content": "Cytosols from 75 normal, 36 abnormal, and 5 decidual human endometrial tissue specimens were assayed for the presence of a high affinity, progesterone-specific binding protein. Thirty of the normal and 15 of the abnormal samples were found to contain a binder which would form a high-affinity complex with progesterone but not with cortisol, 17beta-estradiol, testosterone, or 5alpha-androstane-3-,17-dione. Incubation of cytosol with trypsin or incubation for 2 hours at 37 C abolished [3H]progesterone binding by these preparations, indicating the protein nature and heat-lability of the binder. The average equilibrium constant of dissociation, Kd, of the progesterone-binder complex was 4.0 X 10(-10)M in each phase of the menstrual cycle. The concentration of the binder varied over the cycle, however, with a significant peak at mid-cycle (P = .02). The average saturation values in femtomoles (fmoles)/mg protein ranged from 21 in the early proliferative phase to 64 in the late proliferative samples, dropping to 36 in early secretory and to 3 in the late secretory phase of the cycle. No progesterone-specific binding was detected in decidual samples. Saturable binding was demonstrable in 10 of 22 endometrial hyperplasias, 80-1840 fmoles/mg protein, with high affinity, Kd 3.3 X 10(-10)M. Two other hyperplasia samples bound progesterone, but with lower affinity. Two grade I adenocarcinomas, one grade III adenosquamous carcinoma, and one grade III adenocarcinoma contained the progesterone binder, but in 9 other cancers no detectable binder was present. A benigh adenocanthomyoma was found to contain a progesterone binder (18 fmoles/mg protein with a Kd of 2.5 X 10(-10)M).", "contents": "Progesterone binding by normal and abnormal human endometrium. Cytosols from 75 normal, 36 abnormal, and 5 decidual human endometrial tissue specimens were assayed for the presence of a high affinity, progesterone-specific binding protein. Thirty of the normal and 15 of the abnormal samples were found to contain a binder which would form a high-affinity complex with progesterone but not with cortisol, 17beta-estradiol, testosterone, or 5alpha-androstane-3-,17-dione. Incubation of cytosol with trypsin or incubation for 2 hours at 37 C abolished [3H]progesterone binding by these preparations, indicating the protein nature and heat-lability of the binder. The average equilibrium constant of dissociation, Kd, of the progesterone-binder complex was 4.0 X 10(-10)M in each phase of the menstrual cycle. The concentration of the binder varied over the cycle, however, with a significant peak at mid-cycle (P = .02). The average saturation values in femtomoles (fmoles)/mg protein ranged from 21 in the early proliferative phase to 64 in the late proliferative samples, dropping to 36 in early secretory and to 3 in the late secretory phase of the cycle. No progesterone-specific binding was detected in decidual samples. Saturable binding was demonstrable in 10 of 22 endometrial hyperplasias, 80-1840 fmoles/mg protein, with high affinity, Kd 3.3 X 10(-10)M. Two other hyperplasia samples bound progesterone, but with lower affinity. Two grade I adenocarcinomas, one grade III adenosquamous carcinoma, and one grade III adenocarcinoma contained the progesterone binder, but in 9 other cancers no detectable binder was present. A benigh adenocanthomyoma was found to contain a progesterone binder (18 fmoles/mg protein with a Kd of 2.5 X 10(-10)M)."} {"id": "PMID:177447", "title": "Impaired LH release following exogenous estrogen administration in patients with amenorrhea-galactorrhea syndrome.", "content": "Serum gonadotropin levels were determined in 10 patients with the amenorrhea-galactorrhea syndrome before and following acute iv administration of synthetic LH-releasing hormone (LHRH) or conjugated estrogens, in order to clarify the hypothalamic derangements in the gonadotropin secretion in patients with hyperprolactinemia. The basal prolactin (PRL) levels were elevated in all the patients, and blunted responses to 500 mug of iv synthetic thyrotropin-releasing hormone (TRH) injection were found in 9 out of the 10 patients. The basal levels of LH and FSH were subnormal in 2 and 3 patients, respectively, while those in the remaining patients were normal or slightly elevated. Normal or excessive responses of gonadotropins to 100 mug of iv LHRH were observed in most patients, 9 for LH and 10 for FSH out of 10 patients. In 10 normal cyclic women at the mid-follicular phase (D7-9) and 10 hypothalamic amenorrhea patients without galactorrhea, LH release was found 48 to 72 h after the iv injection of 20 mg conjugated estrogens (Premarin). This LH release following Premarin injection was completely abolished in the patients with amenorrhea-galactorrhea. These data seem to indicate that in patients with hyperprolactinemia, tonic secretion of gonadotropin is maintained fairly well, while of the positive feedback effect of Premarin on the release of LH is impaired. It is suggested that impaired LH release may be partly responsible for anovulation and amenorrhea in patients with hyperprolactinemia.", "contents": "Impaired LH release following exogenous estrogen administration in patients with amenorrhea-galactorrhea syndrome. Serum gonadotropin levels were determined in 10 patients with the amenorrhea-galactorrhea syndrome before and following acute iv administration of synthetic LH-releasing hormone (LHRH) or conjugated estrogens, in order to clarify the hypothalamic derangements in the gonadotropin secretion in patients with hyperprolactinemia. The basal prolactin (PRL) levels were elevated in all the patients, and blunted responses to 500 mug of iv synthetic thyrotropin-releasing hormone (TRH) injection were found in 9 out of the 10 patients. The basal levels of LH and FSH were subnormal in 2 and 3 patients, respectively, while those in the remaining patients were normal or slightly elevated. Normal or excessive responses of gonadotropins to 100 mug of iv LHRH were observed in most patients, 9 for LH and 10 for FSH out of 10 patients. In 10 normal cyclic women at the mid-follicular phase (D7-9) and 10 hypothalamic amenorrhea patients without galactorrhea, LH release was found 48 to 72 h after the iv injection of 20 mg conjugated estrogens (Premarin). This LH release following Premarin injection was completely abolished in the patients with amenorrhea-galactorrhea. These data seem to indicate that in patients with hyperprolactinemia, tonic secretion of gonadotropin is maintained fairly well, while of the positive feedback effect of Premarin on the release of LH is impaired. It is suggested that impaired LH release may be partly responsible for anovulation and amenorrhea in patients with hyperprolactinemia."} {"id": "PMID:177448", "title": "Impaired release of parathyroid hormone in magnesium deficiency.", "content": "Parathyroid hormone release and end-organ responsiveness to parathyroid extract (PTE) were evaluated in a 25-year-old woman with magnesium deficiency associated with hypocalcemia and inappropriately low levels of serum immunoreactive parathyroid hormone (iPTH). End-organ responsiveness to PTE was demonstrated by increases in serum calcium and in urinary phosphorus, cyclic AMP, and hydroxyproline. When the serum calcium was increased from a baseline of 6.9 mg/100 ml to levels of 8.0 mg/100 ml and higher by calcium infusion, the serum iPTH decreased from the low normal range to below the limits of detectability. The intravenous administration of 3 mg/kg of body weight of magnesium led to an abrupt and striking increase in circulating iPTH with a 2-fold increase in one minute, a 6-fold increase in two minutes, and an 8-fold increase in five minutes. The very rapid increase in serum iPTH produced by magnesium infusion in this study suggests an effect of magnesium on hormone secretion rather than an effect on hormone synthesis. The evidence provided by this investigation indicates that the release of parathyroid hormone is impaired in magnesium deficiency and that the level of circulating calcium required for the suppression of parathyroid hormone secretion is lower than that in normal subjects.", "contents": "Impaired release of parathyroid hormone in magnesium deficiency. Parathyroid hormone release and end-organ responsiveness to parathyroid extract (PTE) were evaluated in a 25-year-old woman with magnesium deficiency associated with hypocalcemia and inappropriately low levels of serum immunoreactive parathyroid hormone (iPTH). End-organ responsiveness to PTE was demonstrated by increases in serum calcium and in urinary phosphorus, cyclic AMP, and hydroxyproline. When the serum calcium was increased from a baseline of 6.9 mg/100 ml to levels of 8.0 mg/100 ml and higher by calcium infusion, the serum iPTH decreased from the low normal range to below the limits of detectability. The intravenous administration of 3 mg/kg of body weight of magnesium led to an abrupt and striking increase in circulating iPTH with a 2-fold increase in one minute, a 6-fold increase in two minutes, and an 8-fold increase in five minutes. The very rapid increase in serum iPTH produced by magnesium infusion in this study suggests an effect of magnesium on hormone secretion rather than an effect on hormone synthesis. The evidence provided by this investigation indicates that the release of parathyroid hormone is impaired in magnesium deficiency and that the level of circulating calcium required for the suppression of parathyroid hormone secretion is lower than that in normal subjects."} {"id": "PMID:177449", "title": "A reconsideration of a thyroid-stimulating immunoglobulin as the cause of hyperthyroidism in Graves' disease.", "content": "Several assays for thyroid-stimulating immunoglobulins in the blood in patients with Graves' disease have been described recently; depending upon the method, different names have been used and distinct entities thus implied. Using an increase in cyclic AMP in the human thyroid slice after 2 h of incubation as an index of thyroid stimulation, we identified thyroid-stimulating activity in all of an unselected series of sera from 11 patients with hyperthyroidism of Graves' disease, but long-acting thyroid stimulator, by mouse bioassay, in only three. The theory is proposed that the thyroid-stimulating immunoglobulin is probably present in all such patients; it may be seen as a polyclonal antibody to a single human antigen that has a variable cross-reaction with a corresponding thyroid antigen in the mouse and in other species.", "contents": "A reconsideration of a thyroid-stimulating immunoglobulin as the cause of hyperthyroidism in Graves' disease. Several assays for thyroid-stimulating immunoglobulins in the blood in patients with Graves' disease have been described recently; depending upon the method, different names have been used and distinct entities thus implied. Using an increase in cyclic AMP in the human thyroid slice after 2 h of incubation as an index of thyroid stimulation, we identified thyroid-stimulating activity in all of an unselected series of sera from 11 patients with hyperthyroidism of Graves' disease, but long-acting thyroid stimulator, by mouse bioassay, in only three. The theory is proposed that the thyroid-stimulating immunoglobulin is probably present in all such patients; it may be seen as a polyclonal antibody to a single human antigen that has a variable cross-reaction with a corresponding thyroid antigen in the mouse and in other species."} {"id": "PMID:177450", "title": "Urinary excretion of cyclic adenosine 3',5'-monophosphate in children of different ages.", "content": "The urinary excretion of cyclic AMP was investigated in 97 healthy children, 3 months to 16 years old. When the excretion was expressed as mumol/24 h an increase with age (r = 0.693, P less than 0.001) and an increase with body weight (r = 0.700, P less than 0.001) were found to be quite similar. In relation to surface area, the average excretion for children up to 91/2 years old was 4.45 +/- 1.71 mumol/m2 in constrast with 2.22 +/- 0.66 mumol/m2 in older children (P less than 0.001). The decline appears to be associated with approaching puberty. When cAMP excretion was related to urinary creatinine, an inverse correlation with age was found (r = -0.772, P less than 0.001). In the youngest category, 3 months to 4 years old, the ratio was 9.26 +/- 1.49 mumol/g creatinine vs 4.67 +/- 1.05 mumol/g creatinine in the age group 12 to 16 years old (P less than 0.001), which compares closely with the normal adult average of 4.34 +/- 1.25 mumol/g creatinine found in our previous study. Throughout there was no evidence of sex differentiation.", "contents": "Urinary excretion of cyclic adenosine 3',5'-monophosphate in children of different ages. The urinary excretion of cyclic AMP was investigated in 97 healthy children, 3 months to 16 years old. When the excretion was expressed as mumol/24 h an increase with age (r = 0.693, P less than 0.001) and an increase with body weight (r = 0.700, P less than 0.001) were found to be quite similar. In relation to surface area, the average excretion for children up to 91/2 years old was 4.45 +/- 1.71 mumol/m2 in constrast with 2.22 +/- 0.66 mumol/m2 in older children (P less than 0.001). The decline appears to be associated with approaching puberty. When cAMP excretion was related to urinary creatinine, an inverse correlation with age was found (r = -0.772, P less than 0.001). In the youngest category, 3 months to 4 years old, the ratio was 9.26 +/- 1.49 mumol/g creatinine vs 4.67 +/- 1.05 mumol/g creatinine in the age group 12 to 16 years old (P less than 0.001), which compares closely with the normal adult average of 4.34 +/- 1.25 mumol/g creatinine found in our previous study. Throughout there was no evidence of sex differentiation."} {"id": "PMID:177451", "title": "Viral antibody in the cerebrospinal fluid of patients with acute central nervous system infections.", "content": "Cerebrospinal fluid (CSF) and sera from 129 patients of a study population of 139 were tested for antibody to herpes simplex, measles,and mumps viruses. Herpes simplex virus antibody was found in three of five patients with laboratory-confirmed herpes simplex infection and in eight patients without serological or virological evidence of current infection with this or other common neurotropic visuses. Eleven of the 139 patients were studied for antibody to lymphocytic choriomeningitis (LCM) virus. Eight of these had laboratory-confirmed LCM infection, and antibody was detected in the CSF of five of them. In one of these five, complement-fixing antibody appeared earlier in the CSF than in the blood. Assay of LCM virus antibody in the CSF may thus indicate infection with LCM virus more rapidly than serological and virological studies. The diagnostic and the possible prognostic significance of herpes simplex visus antibody in CSF remains to be ascertained.", "contents": "Viral antibody in the cerebrospinal fluid of patients with acute central nervous system infections. Cerebrospinal fluid (CSF) and sera from 129 patients of a study population of 139 were tested for antibody to herpes simplex, measles,and mumps viruses. Herpes simplex virus antibody was found in three of five patients with laboratory-confirmed herpes simplex infection and in eight patients without serological or virological evidence of current infection with this or other common neurotropic visuses. Eleven of the 139 patients were studied for antibody to lymphocytic choriomeningitis (LCM) virus. Eight of these had laboratory-confirmed LCM infection, and antibody was detected in the CSF of five of them. In one of these five, complement-fixing antibody appeared earlier in the CSF than in the blood. Assay of LCM virus antibody in the CSF may thus indicate infection with LCM virus more rapidly than serological and virological studies. The diagnostic and the possible prognostic significance of herpes simplex visus antibody in CSF remains to be ascertained."} {"id": "PMID:177452", "title": "Exposure of thyroid slices to thyroid-stimulating hormone induces refractoriness of the cyclic AMP system to subsequent hormone stimulation.", "content": "These studies evaluated the influence of an initial exposure of thyroid slices to thyroid-stimulating hormone (TSH) on the subsequent responsiveness to the hormone. Bovine thyroid slices were incubated with or without 50 mU/ml TSH for varying periods and then incubated in hormone-free medium for varying periods. Subsequently, slices were incubated for 20 min with 10 mM theophylline and with or without TSH. Cylic AMP was measured after the third incubation. Phosphodiesterase and adenylate cylase were assayed in homogenates prepared from slices after the second incubation. In some experiments prostaglandin E1, puromycin, thyroxine, and triiodothyronine and propylthiouracil were included in the media. In other experiments, low does of TSH (1 AND 10 mU/ml) were used instead of 50 mU/ml. Slices previously exposed to TSH have decreased responsiveness of the adenylate cyclase-cylic AMP system. Such refractoriness is hormone specific since initial exposure to prostaglandin E1 decreases the subsequent response to this substance but not to TSH. Refractoriness to TSH develops only when the first incubation is at least 30 min. It is not reversed by 5 h of incubation without hormone. Incubation of thyroid slices with puromycin does not eliminate refractoriness. The decreased response to TSH cannot be explained by release of thyroxine, triiodothyronine, or iodide from the slices. Phosphodiesterase activity is not increased during the refractory period. The decreased cyclic AMP response to TSH is associated with diminished response of adenylate cyclase activity to the hormone. Guanosine triphosphate (1 mM) increased adenylate cyclase activity in both control and TSH treated tissue, but the effect was significantly less in the latter. Although with guanosine triphosphate, TSH increased adenylate cyclase activity in TSH treated tissue, the enzyme activity was still less than that present in control tissue incubated with guanosine triphosphate and TSH. NaF caused an equivalent stimulation of adenylate cyclase in both control and TSH treated tissue. These results suggest that the refractoriness represents an alteration in hormone binding or the coupling of the bound hormone to the adenylate cyclase activity rather than any modification of the catalytic site of the enzyme.", "contents": "Exposure of thyroid slices to thyroid-stimulating hormone induces refractoriness of the cyclic AMP system to subsequent hormone stimulation. These studies evaluated the influence of an initial exposure of thyroid slices to thyroid-stimulating hormone (TSH) on the subsequent responsiveness to the hormone. Bovine thyroid slices were incubated with or without 50 mU/ml TSH for varying periods and then incubated in hormone-free medium for varying periods. Subsequently, slices were incubated for 20 min with 10 mM theophylline and with or without TSH. Cylic AMP was measured after the third incubation. Phosphodiesterase and adenylate cylase were assayed in homogenates prepared from slices after the second incubation. In some experiments prostaglandin E1, puromycin, thyroxine, and triiodothyronine and propylthiouracil were included in the media. In other experiments, low does of TSH (1 AND 10 mU/ml) were used instead of 50 mU/ml. Slices previously exposed to TSH have decreased responsiveness of the adenylate cyclase-cylic AMP system. Such refractoriness is hormone specific since initial exposure to prostaglandin E1 decreases the subsequent response to this substance but not to TSH. Refractoriness to TSH develops only when the first incubation is at least 30 min. It is not reversed by 5 h of incubation without hormone. Incubation of thyroid slices with puromycin does not eliminate refractoriness. The decreased response to TSH cannot be explained by release of thyroxine, triiodothyronine, or iodide from the slices. Phosphodiesterase activity is not increased during the refractory period. The decreased cyclic AMP response to TSH is associated with diminished response of adenylate cyclase activity to the hormone. Guanosine triphosphate (1 mM) increased adenylate cyclase activity in both control and TSH treated tissue, but the effect was significantly less in the latter. Although with guanosine triphosphate, TSH increased adenylate cyclase activity in TSH treated tissue, the enzyme activity was still less than that present in control tissue incubated with guanosine triphosphate and TSH. NaF caused an equivalent stimulation of adenylate cyclase in both control and TSH treated tissue. These results suggest that the refractoriness represents an alteration in hormone binding or the coupling of the bound hormone to the adenylate cyclase activity rather than any modification of the catalytic site of the enzyme."} {"id": "PMID:177453", "title": "Decreased insulin binding to adipocytes and circulating monocytes from obese subjects.", "content": "Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity in childhood. When these five patients were separated from the original 14 obese patients, enhanced differences in insulin binding to adipocytes were observed when normals and the remaining 9 obese subjects were compared. Similar findings were obtained with isolated circulating mononuclear cells from these same patients. Presumably the five normoinsulinemic obese patients were not insulin-resistant, and, thus, the data indicate that insulin binding to adipocytes was decreased only in insulin-resistant obese patients. This conclusion was strengthened by finding a highly significant correlation (r=-0.71, p less than 0.001) between insulin binding to adipocytes and fasting plasma insulin level, while a weaker correlation (r=-0.49,p less than 0.01) existed between insulin binding and degree of obesity. Finally, when insulin binding to adipocytes and mononuclear cells from the same individual was compared, a significant positive correlation was found (r=0.53,p less than 0.01). (a) insulin binding to adipocytes and mononuclear cells is decreased in cells from insulin-resistant obese patients; (b) a significant inverse relationship exists between fasting plasma insulin level and insulin binding to adipocytes; and (c) in obesity, events that affect insulin receptors on adipocytes similarly affect insulin receptors on mononuclear cells.", "contents": "Decreased insulin binding to adipocytes and circulating monocytes from obese subjects. Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity in childhood. When these five patients were separated from the original 14 obese patients, enhanced differences in insulin binding to adipocytes were observed when normals and the remaining 9 obese subjects were compared. Similar findings were obtained with isolated circulating mononuclear cells from these same patients. Presumably the five normoinsulinemic obese patients were not insulin-resistant, and, thus, the data indicate that insulin binding to adipocytes was decreased only in insulin-resistant obese patients. This conclusion was strengthened by finding a highly significant correlation (r=-0.71, p less than 0.001) between insulin binding to adipocytes and fasting plasma insulin level, while a weaker correlation (r=-0.49,p less than 0.01) existed between insulin binding and degree of obesity. Finally, when insulin binding to adipocytes and mononuclear cells from the same individual was compared, a significant positive correlation was found (r=0.53,p less than 0.01). (a) insulin binding to adipocytes and mononuclear cells is decreased in cells from insulin-resistant obese patients; (b) a significant inverse relationship exists between fasting plasma insulin level and insulin binding to adipocytes; and (c) in obesity, events that affect insulin receptors on adipocytes similarly affect insulin receptors on mononuclear cells."} {"id": "PMID:177454", "title": "Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.", "content": "Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product.", "contents": "Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance. Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product."} {"id": "PMID:177455", "title": "The differential impact of work-oriented vs. communication-oriented juvenile correction programs upon recidivism rates in delinquent males.", "content": "This study examined recidivism rates in work-oriented (N = 30) and communication-oriented (N = 30) juvenile delinquency programs for males. Both groups were matched for age, ethnic origin, educational achievement, and reading scores. Chi-square analyses indicated significant differences in recidivism rates between groups in both residential (chi2 - 6.71, df = 1, p less than .01) and aftercare (chi2 = 3.89, df = 1, p less than .05) programs. In each phase of the treatment program, recidivism was highest in the work-oriented group. The results suggested that (a) facilitation of family interaction and communication is related closely to successful treatment of the delinquent and consequent recidivism; (b) group counseling that provides the youth and parents an opportunity to learn better communication skills appears to improve family cohesion and solidarity; and (c) newer therapeutic approaches in delinquency should concentrate on filial and family-type therapies.", "contents": "The differential impact of work-oriented vs. communication-oriented juvenile correction programs upon recidivism rates in delinquent males. This study examined recidivism rates in work-oriented (N = 30) and communication-oriented (N = 30) juvenile delinquency programs for males. Both groups were matched for age, ethnic origin, educational achievement, and reading scores. Chi-square analyses indicated significant differences in recidivism rates between groups in both residential (chi2 - 6.71, df = 1, p less than .01) and aftercare (chi2 = 3.89, df = 1, p less than .05) programs. In each phase of the treatment program, recidivism was highest in the work-oriented group. The results suggested that (a) facilitation of family interaction and communication is related closely to successful treatment of the delinquent and consequent recidivism; (b) group counseling that provides the youth and parents an opportunity to learn better communication skills appears to improve family cohesion and solidarity; and (c) newer therapeutic approaches in delinquency should concentrate on filial and family-type therapies."} {"id": "PMID:177456", "title": "The binding of cyclic AMP to renal brush border membranes.", "content": "The binding of cyclic AMP to the proximal tubule luminal (brush border) membrane isolated from the rabbit renal cortex was studied. The rate of binding was dependent on temperature; at 37 degrees equilibrium was attained in 45 min, whereas at 0 degrees 120 min was required. The final levels of binding were identical. The binding of 3H-cyclic AMP was reversed by dilution or addition of unlabeled cyclic nucleotide. Debinding was markedly temperature sensitive. Binding was only partially saturable with respect to cyclic AMP concentration, apparently with more than one binding site. The cyclic AMP bound to the membrane was recovered unchanged. When bound to the membrane cyclic AMP was resistant to hydrolysis by endogenous membrane or exogenously added phosphodiesterase. The binding to the membranes was relatively specific for cyclic AMP, although other cyclic purine nucleotides inhibited, cyclic IMP greater than dibutyryl cyclic AMP greater than cyclic GMP. The renal membranes did bind cyclic GMP, but this binding was relatively non-specific. Hormones and drugs, that mediate cyclic AMP generation or renal function, as well as other compounds common to the proximal tubule were without significant effect on cyclic AMP binding. Binding was inhibited by sulfhydryl reacting agents and this inhibition could be blocked and partially reversed by mercaptoethanol.", "contents": "The binding of cyclic AMP to renal brush border membranes. The binding of cyclic AMP to the proximal tubule luminal (brush border) membrane isolated from the rabbit renal cortex was studied. The rate of binding was dependent on temperature; at 37 degrees equilibrium was attained in 45 min, whereas at 0 degrees 120 min was required. The final levels of binding were identical. The binding of 3H-cyclic AMP was reversed by dilution or addition of unlabeled cyclic nucleotide. Debinding was markedly temperature sensitive. Binding was only partially saturable with respect to cyclic AMP concentration, apparently with more than one binding site. The cyclic AMP bound to the membrane was recovered unchanged. When bound to the membrane cyclic AMP was resistant to hydrolysis by endogenous membrane or exogenously added phosphodiesterase. The binding to the membranes was relatively specific for cyclic AMP, although other cyclic purine nucleotides inhibited, cyclic IMP greater than dibutyryl cyclic AMP greater than cyclic GMP. The renal membranes did bind cyclic GMP, but this binding was relatively non-specific. Hormones and drugs, that mediate cyclic AMP generation or renal function, as well as other compounds common to the proximal tubule were without significant effect on cyclic AMP binding. Binding was inhibited by sulfhydryl reacting agents and this inhibition could be blocked and partially reversed by mercaptoethanol."} {"id": "PMID:177457", "title": "LH and FSH stimulation of cyclic AMP in specific cell types isolated from the testes.", "content": "The direct effect of LH and FSH on cyclic AMP levels in specific cell types, isolated from the rat testes, was investigated in vitro. LH significantly stimulated cyclic AMP production in isolated interstitial cells and had only a slight effect on the isolated germ cells. FSH significantly stimulated cyclic AMP production in isolated seminiferous tubules, organ cultures of testes explants, and isolated Sertoli cells, with only a small response elicited in the germ cells. FSH had no effect on the cyclic AMP levels in interstitial cells and either freshly isolated or cultured peritubular cells. These data indicate that the Sertoli cells and interstitial cells are the main cell types in the testes which respond to FSH and LH respectively with increased cyclic AMP production. A possible slight effect of either hormone on the cyclic AMP level in the germ cells has not be ruled out.", "contents": "LH and FSH stimulation of cyclic AMP in specific cell types isolated from the testes. The direct effect of LH and FSH on cyclic AMP levels in specific cell types, isolated from the rat testes, was investigated in vitro. LH significantly stimulated cyclic AMP production in isolated interstitial cells and had only a slight effect on the isolated germ cells. FSH significantly stimulated cyclic AMP production in isolated seminiferous tubules, organ cultures of testes explants, and isolated Sertoli cells, with only a small response elicited in the germ cells. FSH had no effect on the cyclic AMP levels in interstitial cells and either freshly isolated or cultured peritubular cells. These data indicate that the Sertoli cells and interstitial cells are the main cell types in the testes which respond to FSH and LH respectively with increased cyclic AMP production. A possible slight effect of either hormone on the cyclic AMP level in the germ cells has not be ruled out."} {"id": "PMID:177458", "title": "Inhibition of cyclic nucleotide phosphodiesterase activity by an endogenous factor.", "content": "Cyclic nucleotide phosphodiesterase activity of several tissues of rat is inhibited by an endogenous factor isolated from rat adipocytes following exposure of these cells to agents that raise intracellular cyclic AMP levels. The inhibitory action was demonstrated with varying cAMP concentrations from 0.1-400 muM. Enzyme from 10,000 X g supernatant of epididymal adipose tissue was inhibited approximately 2-3 fold more than the plasma membrane of adipocytes by a given concentration of the feedback regulator. Kinetic analysis of cAMP phosphodiesterase of plasma membrane showed that feedback regulator (8.8 U/ml) inhibited the Vmax 48%. The maximum inhibition of phosphodiesterase by feedback regulator (20 U/ml) was about 80%. The apparent Km for cAMP was increased. The ability of phosphodiesterase from several tissues of rat (10,000 X g supernatant) to hydrolyze cAMP and cGMP was tested. Feedback regulator inhibited cGMP hydrolysis in cardiac muscle and 5 other tissues 23-92% more than it inhibited the hydrolysis of cAMP. The physiological significance of this inhibitory effect can begin to be clarified when the feedback regulator is purified to homogeneity and characterized.", "contents": "Inhibition of cyclic nucleotide phosphodiesterase activity by an endogenous factor. Cyclic nucleotide phosphodiesterase activity of several tissues of rat is inhibited by an endogenous factor isolated from rat adipocytes following exposure of these cells to agents that raise intracellular cyclic AMP levels. The inhibitory action was demonstrated with varying cAMP concentrations from 0.1-400 muM. Enzyme from 10,000 X g supernatant of epididymal adipose tissue was inhibited approximately 2-3 fold more than the plasma membrane of adipocytes by a given concentration of the feedback regulator. Kinetic analysis of cAMP phosphodiesterase of plasma membrane showed that feedback regulator (8.8 U/ml) inhibited the Vmax 48%. The maximum inhibition of phosphodiesterase by feedback regulator (20 U/ml) was about 80%. The apparent Km for cAMP was increased. The ability of phosphodiesterase from several tissues of rat (10,000 X g supernatant) to hydrolyze cAMP and cGMP was tested. Feedback regulator inhibited cGMP hydrolysis in cardiac muscle and 5 other tissues 23-92% more than it inhibited the hydrolysis of cAMP. The physiological significance of this inhibitory effect can begin to be clarified when the feedback regulator is purified to homogeneity and characterized."} {"id": "PMID:177459", "title": "The functions of cyclic AMP and calcium as alternative second messengers in parotid gland and pancreas.", "content": "Biochemical and ultrastructural studies of rat parotid gland slices have led to the identification of alpha- and beta-adrenergic receptors and a cholinergic receptor, all operating within the same secretory cell. While cyclic AMP serves as the second messenger in the beta-adrenergic response of enzyme secretion, Ca++ serves as the second messenger in the alpha-adrenergic and in the cholinergic responses which both lead to K+ release and water secretion. Ca++ also serves as a second messenger for the muscarinic cholinergic receptor in rat pancreas slices in which it causes enzyme secretion. Analysis of this information leads to the conclusion that neither the neurotransmitter, nor the receptor, nor the second messenger are unique for a certain type of response. The latter seems to be dictated by a component of the specific response pathway which is affected by the second or a subsequent messenger. By having different neurotransmitters operate the same response and a single neurotransmitter operate different responses diversity of control is achieved.", "contents": "The functions of cyclic AMP and calcium as alternative second messengers in parotid gland and pancreas. Biochemical and ultrastructural studies of rat parotid gland slices have led to the identification of alpha- and beta-adrenergic receptors and a cholinergic receptor, all operating within the same secretory cell. While cyclic AMP serves as the second messenger in the beta-adrenergic response of enzyme secretion, Ca++ serves as the second messenger in the alpha-adrenergic and in the cholinergic responses which both lead to K+ release and water secretion. Ca++ also serves as a second messenger for the muscarinic cholinergic receptor in rat pancreas slices in which it causes enzyme secretion. Analysis of this information leads to the conclusion that neither the neurotransmitter, nor the receptor, nor the second messenger are unique for a certain type of response. The latter seems to be dictated by a component of the specific response pathway which is affected by the second or a subsequent messenger. By having different neurotransmitters operate the same response and a single neurotransmitter operate different responses diversity of control is achieved."} {"id": "PMID:177460", "title": "The effects of hormones on cyclic adenosine 3':5'-monophosphate accumulation in transitional epithelium of the urinary bladder.", "content": "Transitional epithelium lining rabbit urinary bladders was isolated and studied in vitro. The homogeneity of the isolated epithelium was demonstrated by light and electron microscopical monitoring as well as cell culture studies. Transitional epithelium responded to epinephrine and prostaglandin E1 (PGE1) in the presence of 2mM 1-methyl, 3-isobutylxanthine (MIX) with increases in intracellular levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Corticotropin, aldosterone, insulin, parathyroid hormone and vasopressin were slightly but significantly stimulatory under similar conditions. Glucagon and oxytocin were not stimulatory at the concentrations tested. The effects of epinephrine and PGE1 were potentiated by 2mM MIX 20-fold or greater. The cells were slightly more sensitive to PGE1 then to epinephrine. The prostaglandin produced a noticeable response at about 10nM, while effects of epinephrine were discernible at 0.1muM. Maximal responses to both effectors were seen at about 10muM. The action of 10muM epinephrine, but not 10muM PGE1, was completely abolished by 0.1mM propranolol. Responses to combinations of epinephrine and PGE1 were additive. Cyclic AMP accumulated in the incubation medium of transitional epithelial cells exposed to epinephrine, PGE1, MIX, or combinations of the agonists. The appearance of cyclic AMP in the medium was slow compared to the rate of intracellular accumulation, but reached significant levels following prolonged stimulation.", "contents": "The effects of hormones on cyclic adenosine 3':5'-monophosphate accumulation in transitional epithelium of the urinary bladder. Transitional epithelium lining rabbit urinary bladders was isolated and studied in vitro. The homogeneity of the isolated epithelium was demonstrated by light and electron microscopical monitoring as well as cell culture studies. Transitional epithelium responded to epinephrine and prostaglandin E1 (PGE1) in the presence of 2mM 1-methyl, 3-isobutylxanthine (MIX) with increases in intracellular levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Corticotropin, aldosterone, insulin, parathyroid hormone and vasopressin were slightly but significantly stimulatory under similar conditions. Glucagon and oxytocin were not stimulatory at the concentrations tested. The effects of epinephrine and PGE1 were potentiated by 2mM MIX 20-fold or greater. The cells were slightly more sensitive to PGE1 then to epinephrine. The prostaglandin produced a noticeable response at about 10nM, while effects of epinephrine were discernible at 0.1muM. Maximal responses to both effectors were seen at about 10muM. The action of 10muM epinephrine, but not 10muM PGE1, was completely abolished by 0.1mM propranolol. Responses to combinations of epinephrine and PGE1 were additive. Cyclic AMP accumulated in the incubation medium of transitional epithelial cells exposed to epinephrine, PGE1, MIX, or combinations of the agonists. The appearance of cyclic AMP in the medium was slow compared to the rate of intracellular accumulation, but reached significant levels following prolonged stimulation."} {"id": "PMID:177461", "title": "Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution.", "content": "The sensitivity of radioimmunoassays for cyclic AMP and cyclic GMP has been markedly improved to readily detect femtomole (10-15) amounts in tissue extracts by acetylating the cyclic nucleotides at the 2'0 position with acetic anhydride. Acetylation of cyclic nucleotides by acetic anhydride in aqueous solution proceeds more rapidly than the hydrolysis of acetic anhydride to acetic acid thus yielding 100% acetylated cyclic nucleotide. 2'0 substituted cyclic nucleotides have greater affinity for the antibody than the parent cyclic nucleotides because the antibody has been made to a protein conjugate coupled at the 2'0 position. This simple acetylation technique makes it possible to measure cyclic AMP and cyclic GMP in minute quantities of tissue without purification or concentration of the sample.", "contents": "Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution. The sensitivity of radioimmunoassays for cyclic AMP and cyclic GMP has been markedly improved to readily detect femtomole (10-15) amounts in tissue extracts by acetylating the cyclic nucleotides at the 2'0 position with acetic anhydride. Acetylation of cyclic nucleotides by acetic anhydride in aqueous solution proceeds more rapidly than the hydrolysis of acetic anhydride to acetic acid thus yielding 100% acetylated cyclic nucleotide. 2'0 substituted cyclic nucleotides have greater affinity for the antibody than the parent cyclic nucleotides because the antibody has been made to a protein conjugate coupled at the 2'0 position. This simple acetylation technique makes it possible to measure cyclic AMP and cyclic GMP in minute quantities of tissue without purification or concentration of the sample."} {"id": "PMID:177462", "title": "The effect of Ca++ on cyclic nucleotide phosphodiesterases of superior cervical ganglion.", "content": "Cyclic nucleotide phosphodiesterase was examined in canine and bovine superior cervical ganglia. Activity in crude supernatant fractions was only slightly stimulated by Ca++ despite the presence of protein activating factor. Three forms of phosphodiesterase were resolved from bovine ganglia supernatant extracts by chromatography on DEAE-cellulose. The first enzyme eluted, (DI), was almost completely specific for cyclic GMP, while the other two (DII and DIII), hydrolyzed both cyclic AMP and cyclic GMP; all were free of heat-stable protein activator. Each enzyme was inhibited by low concentrations of Ca++ in the assay medium. Inhibition by Ca++ was reversed by addition of protein activator, but activity did not increase above the control level. Cyclic AMP hydrolysis by enzyme DII was stimulated by micromolar concentrations of cyclic GMP. This stimulation was reduced by Ca++ unless protein activator was present.", "contents": "The effect of Ca++ on cyclic nucleotide phosphodiesterases of superior cervical ganglion. Cyclic nucleotide phosphodiesterase was examined in canine and bovine superior cervical ganglia. Activity in crude supernatant fractions was only slightly stimulated by Ca++ despite the presence of protein activating factor. Three forms of phosphodiesterase were resolved from bovine ganglia supernatant extracts by chromatography on DEAE-cellulose. The first enzyme eluted, (DI), was almost completely specific for cyclic GMP, while the other two (DII and DIII), hydrolyzed both cyclic AMP and cyclic GMP; all were free of heat-stable protein activator. Each enzyme was inhibited by low concentrations of Ca++ in the assay medium. Inhibition by Ca++ was reversed by addition of protein activator, but activity did not increase above the control level. Cyclic AMP hydrolysis by enzyme DII was stimulated by micromolar concentrations of cyclic GMP. This stimulation was reduced by Ca++ unless protein activator was present."} {"id": "PMID:177463", "title": "PGE1-mediated cyclic AMP refractoriness: effects of cycloheximide and indomethacin.", "content": "Human synoviocytes in culture respond to prostaglandin E1 (PGE1) by increasing their intracellular concentration of cyclic AMP. Readdition of PGE1 to cells previously treated with PGE1 elicits no change in the intracellular concentration of cyclic AMP. This refractory state is partially prevented by the inhibitors of protein synthesis, puromycin (PM) and cycloheximide (CH). Indomethacin (IM), which reduces angiotensin tachyphylaxis, does not prevent the occurrence of refractoriness to PGE1 with respect to accumulation of cyclic AMP. This agent does alter the release of cyclic AMP from human synovial cells. We postulate that other factors, independent of new protein synthesis, are necessary for the development of the complete PGE1 refractory state in these cells.", "contents": "PGE1-mediated cyclic AMP refractoriness: effects of cycloheximide and indomethacin. Human synoviocytes in culture respond to prostaglandin E1 (PGE1) by increasing their intracellular concentration of cyclic AMP. Readdition of PGE1 to cells previously treated with PGE1 elicits no change in the intracellular concentration of cyclic AMP. This refractory state is partially prevented by the inhibitors of protein synthesis, puromycin (PM) and cycloheximide (CH). Indomethacin (IM), which reduces angiotensin tachyphylaxis, does not prevent the occurrence of refractoriness to PGE1 with respect to accumulation of cyclic AMP. This agent does alter the release of cyclic AMP from human synovial cells. We postulate that other factors, independent of new protein synthesis, are necessary for the development of the complete PGE1 refractory state in these cells."} {"id": "PMID:177464", "title": "Alterations in the hydrolytic activity, inhibitor sensitivity and molecular size of the rat erythrocyte cyclic AMP phosphodiesterase by calcium and hypertonic sodium chloride.", "content": "Hypertonic NaCl irreversibly reduced the sensitivity of the rat erythrocyte cyclic AMP phosphodiesterase to inhibition by Ro 20-1724 but not by papavarine. This effect could be prevented by 1 mM EDTA and mimicked by by CaCl2. The reduction in inhibitor sensitivity was associated with an increase in hydrolytic activity and a four-fold reduction in molecular weight as estimated by Sephadex G-200 chromatography. The response to CaCl2, like that to NaCl, was time and concentration dependent and proceeded more slowly in 2 M NaCl. This concentration of NaCl contained sufficient Ca++ as an impurity to account for its effects on inhibitor sensitivity and molecular size. However, the initial and reversible increase in inhibitor sensitivity and hydrolytic activity obtained in the presence of EDTA, probably resulted from the high salt concentration, per se.", "contents": "Alterations in the hydrolytic activity, inhibitor sensitivity and molecular size of the rat erythrocyte cyclic AMP phosphodiesterase by calcium and hypertonic sodium chloride. Hypertonic NaCl irreversibly reduced the sensitivity of the rat erythrocyte cyclic AMP phosphodiesterase to inhibition by Ro 20-1724 but not by papavarine. This effect could be prevented by 1 mM EDTA and mimicked by by CaCl2. The reduction in inhibitor sensitivity was associated with an increase in hydrolytic activity and a four-fold reduction in molecular weight as estimated by Sephadex G-200 chromatography. The response to CaCl2, like that to NaCl, was time and concentration dependent and proceeded more slowly in 2 M NaCl. This concentration of NaCl contained sufficient Ca++ as an impurity to account for its effects on inhibitor sensitivity and molecular size. However, the initial and reversible increase in inhibitor sensitivity and hydrolytic activity obtained in the presence of EDTA, probably resulted from the high salt concentration, per se."} {"id": "PMID:177465", "title": "Prostaglandin synthetase activity and hormone responsiveness in normal and SV40 transformed WI-38 fibroblasts.", "content": "Prostaglandin (PG) synthetase activity and selective hormone responsiveness were examined in normal and SV40 transformed WI-38 fibroblasts (VA13-2RA). The transformed VA13-2RA cells have significantly reduced rates of PGE1, PGE2, PGF1alpha and PGF2alpha synthesis as compared to the normal WI-38 fibroblast. The transformed cell in contrast to the normal cell hyperresponds to stimulation by L-epinephrine (10 muM) and PGE1 (8.5 muM) but is unresponsive to bradykinin (BK) as measured by the accumulation of intracellular cyclic AMP. Indomethacin treatment does not significantly alter the PGE1 and L-epinephrine (EPI) responsiveness of the normal WI-38 fibroblast, however it abolishes the BK response in these cells. These results provide further evidence for the dependency of cell activation by bradykinin on the PG synthetase system. No experimental data was found to support the role of PGs as negative regulators of PGE1 and EPI responsiveness in the WI-38 fibroblast. Using the VA13-2RA cells, limited attempts to recover PG synthetase activity comparable to that found in normal WI-38 cells were unsuccessful. The VA13-2RA cell and its normal counterpart represent models for investigating the role of PGs in cell function and the mechanism of BK activation and its effect on cell metabolism.", "contents": "Prostaglandin synthetase activity and hormone responsiveness in normal and SV40 transformed WI-38 fibroblasts. Prostaglandin (PG) synthetase activity and selective hormone responsiveness were examined in normal and SV40 transformed WI-38 fibroblasts (VA13-2RA). The transformed VA13-2RA cells have significantly reduced rates of PGE1, PGE2, PGF1alpha and PGF2alpha synthesis as compared to the normal WI-38 fibroblast. The transformed cell in contrast to the normal cell hyperresponds to stimulation by L-epinephrine (10 muM) and PGE1 (8.5 muM) but is unresponsive to bradykinin (BK) as measured by the accumulation of intracellular cyclic AMP. Indomethacin treatment does not significantly alter the PGE1 and L-epinephrine (EPI) responsiveness of the normal WI-38 fibroblast, however it abolishes the BK response in these cells. These results provide further evidence for the dependency of cell activation by bradykinin on the PG synthetase system. No experimental data was found to support the role of PGs as negative regulators of PGE1 and EPI responsiveness in the WI-38 fibroblast. Using the VA13-2RA cells, limited attempts to recover PG synthetase activity comparable to that found in normal WI-38 cells were unsuccessful. The VA13-2RA cell and its normal counterpart represent models for investigating the role of PGs in cell function and the mechanism of BK activation and its effect on cell metabolism."} {"id": "PMID:177466", "title": "Cyclic guanosine 3':5'-monophosphate and the regulation of lipolysis in rat fat cells.", "content": "The addition of the divalent cation ionophore A23187, carbachol, norepinephrine or insulin to rat fat cells elevated cyclic GMP. The increase in cyclic GMP due to these agents was greater at 4 than at 2 minutes after their addition. Cyclic GMP accumulation was also elevated by the addition of 0.1 to 0.5 mM sodium oleate in the presence of 0.1% albumin and by albumin containing added palmitate with an FFA/albumin molar ratio of 6.7. The rise in cyclic GMP due to all agents was markedly reduced in calcium-free buffer. The effects of the various agents on cyclic GMP accumulation in rat fat cells had little correlation with lipolysis. Insulin was an effective anti-lipolytic agent in both the presence and absence of calcium while neither A23187 nor carbachol had any effect on fat cell lipolysis.", "contents": "Cyclic guanosine 3':5'-monophosphate and the regulation of lipolysis in rat fat cells. The addition of the divalent cation ionophore A23187, carbachol, norepinephrine or insulin to rat fat cells elevated cyclic GMP. The increase in cyclic GMP due to these agents was greater at 4 than at 2 minutes after their addition. Cyclic GMP accumulation was also elevated by the addition of 0.1 to 0.5 mM sodium oleate in the presence of 0.1% albumin and by albumin containing added palmitate with an FFA/albumin molar ratio of 6.7. The rise in cyclic GMP due to all agents was markedly reduced in calcium-free buffer. The effects of the various agents on cyclic GMP accumulation in rat fat cells had little correlation with lipolysis. Insulin was an effective anti-lipolytic agent in both the presence and absence of calcium while neither A23187 nor carbachol had any effect on fat cell lipolysis."} {"id": "PMID:177467", "title": "Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2.", "content": "The effects of prostaglandin E1 and prostaglandin G2, the prostaglandin endoperoxide, on platelet cyclic nucleotide concentrations were measured in platelet rich plasma (PRP), and in washed intact platelets. PGE1 was found to be a potent stimulator of platelet cAMP levels in both PRP and washed cells, and to inhibit aggregation in both systems. PGE1 did not change platelet cGMP levels in either PRP or washed cells. PGG2 which is a potent inducer of platelet aggregation, did not affect either the basal cAMP or the basal cGMP concentration. However, PGG2 was found to antagonize the increases in cAMP content in response to PGE1 in both PRP and washed platelets. The addition to our system of a cyclic nucleotide phosphodiesterase inhbitor, theophylline, did not change our findings. It is suggested that PGG2 may induce platelet aggregation by inhibiting PGE1-stimulated cAMP accumulation.", "contents": "Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2. The effects of prostaglandin E1 and prostaglandin G2, the prostaglandin endoperoxide, on platelet cyclic nucleotide concentrations were measured in platelet rich plasma (PRP), and in washed intact platelets. PGE1 was found to be a potent stimulator of platelet cAMP levels in both PRP and washed cells, and to inhibit aggregation in both systems. PGE1 did not change platelet cGMP levels in either PRP or washed cells. PGG2 which is a potent inducer of platelet aggregation, did not affect either the basal cAMP or the basal cGMP concentration. However, PGG2 was found to antagonize the increases in cAMP content in response to PGE1 in both PRP and washed platelets. The addition to our system of a cyclic nucleotide phosphodiesterase inhbitor, theophylline, did not change our findings. It is suggested that PGG2 may induce platelet aggregation by inhibiting PGE1-stimulated cAMP accumulation."} {"id": "PMID:177468", "title": "Growth of astrocytoma cells in the presence of prostaglandin E1: effect on the regulation of cyclic AMP metabolism.", "content": "Human astrocytoma cells (1321N1) in culture respond to pharmacological concentrations of prostaglandins and catecholamines with a marked increase in the accumulation of cyclic AMP. However, growth of 1321N1 cells in the presence of low concentrations (0.003 to 0.1 muM) of prostaglandin E1 (PGE1) results in a marked reduction in the responsiveness of the cells-even to concentrations of PGE1 that normally stimulate maximal accumulation of cyclic AMP. Occasionally, a partial reduction in the responsiveness to catecholamines was observed in cells grown in the presence of PGE1. When it occurred this effect could be correlated with an increase in the cyclic AMP-degradation capacity of the cells. This loss of responsiveness to catecholamines could be completely reversed by 1-methyl-3-isobutylxanthine, a potent inhibitor of phosphodiesterase activity in 1321N1 cells. The consistently observed and more profound desensitization to the effects of PGE1 could not be correlated with an increase in cyclic AM-degradative capacity. Accordingly, 1-methyl-3-isobutylxanthine was only minimally effective in reversing desensitization to PGE1. It is concluded that the inability of 1321N1 cells grown in the presence of PGE1 to accumulate cyclic AMP upon subsequent challenge with PGE1 is primarily due to a selective desensitization of the PGE1-activated adenylate cyclase.", "contents": "Growth of astrocytoma cells in the presence of prostaglandin E1: effect on the regulation of cyclic AMP metabolism. Human astrocytoma cells (1321N1) in culture respond to pharmacological concentrations of prostaglandins and catecholamines with a marked increase in the accumulation of cyclic AMP. However, growth of 1321N1 cells in the presence of low concentrations (0.003 to 0.1 muM) of prostaglandin E1 (PGE1) results in a marked reduction in the responsiveness of the cells-even to concentrations of PGE1 that normally stimulate maximal accumulation of cyclic AMP. Occasionally, a partial reduction in the responsiveness to catecholamines was observed in cells grown in the presence of PGE1. When it occurred this effect could be correlated with an increase in the cyclic AMP-degradation capacity of the cells. This loss of responsiveness to catecholamines could be completely reversed by 1-methyl-3-isobutylxanthine, a potent inhibitor of phosphodiesterase activity in 1321N1 cells. The consistently observed and more profound desensitization to the effects of PGE1 could not be correlated with an increase in cyclic AM-degradative capacity. Accordingly, 1-methyl-3-isobutylxanthine was only minimally effective in reversing desensitization to PGE1. It is concluded that the inability of 1321N1 cells grown in the presence of PGE1 to accumulate cyclic AMP upon subsequent challenge with PGE1 is primarily due to a selective desensitization of the PGE1-activated adenylate cyclase."} {"id": "PMID:177469", "title": "On the accumulation of adenosine 3':5'-monophosphate in Ehrlich cells and adenylate cyclase desensitization in response to epinephrine.", "content": "The time course of the action of epinephrine on cAMP levels in isolated mouse Ehrlich ascites cells was studied. Following the addition of hormone (10(-7) to 10(-4) M), cAMP levels reached a maximum within 1 min and declined to about 2 fold basal levels within 10-20 min. The decline phase was not due to the metabolism of epinephrine or accumulation of an inhibitor in the medium. Experiments involving timed additions of theophylline to epinephrine-treated cells suggested that the rate of cAMP synthesis declined progressively with time. Cells treated with epinephrine and then washed free of hormone were shown to be refractory to hormonal stimulation of cAMP levels. Adenylate cyclase prepared from epinephrine-treated cells was shown to exhibit decreased sensitivity to the hormone in in vitro incubations. Resensitization of the enzyme could be achieved by washing pretreated cells free of epinephrine and reincubating them for 1/2 to 2 h. Neither desensitization nor resensitization were prevented by cycloheximide or actinomycin D. Desensitization could not be induced by incubating cels with dibutyryl-cAMP. The desensitization phenomenon is considered to be a mechanism whereby cells protect themselves against the possible harmful effects of high levels of cAMP maintained over a long period of time.", "contents": "On the accumulation of adenosine 3':5'-monophosphate in Ehrlich cells and adenylate cyclase desensitization in response to epinephrine. The time course of the action of epinephrine on cAMP levels in isolated mouse Ehrlich ascites cells was studied. Following the addition of hormone (10(-7) to 10(-4) M), cAMP levels reached a maximum within 1 min and declined to about 2 fold basal levels within 10-20 min. The decline phase was not due to the metabolism of epinephrine or accumulation of an inhibitor in the medium. Experiments involving timed additions of theophylline to epinephrine-treated cells suggested that the rate of cAMP synthesis declined progressively with time. Cells treated with epinephrine and then washed free of hormone were shown to be refractory to hormonal stimulation of cAMP levels. Adenylate cyclase prepared from epinephrine-treated cells was shown to exhibit decreased sensitivity to the hormone in in vitro incubations. Resensitization of the enzyme could be achieved by washing pretreated cells free of epinephrine and reincubating them for 1/2 to 2 h. Neither desensitization nor resensitization were prevented by cycloheximide or actinomycin D. Desensitization could not be induced by incubating cels with dibutyryl-cAMP. The desensitization phenomenon is considered to be a mechanism whereby cells protect themselves against the possible harmful effects of high levels of cAMP maintained over a long period of time."} {"id": "PMID:177470", "title": "Acetaldehyde: an intermediate in the formation of ethanol from glucose by lactic acid bacteria.", "content": "Group N streptococci formed acetaldehyde and ethanol from glucose. As the enzymes aldehyde dehydrogenase, phosphotransacetylase and acetate kinase were present this would enable these organisms to reduce acetyl-CoA to acetaldehyde and convert acetyl-CoA to acetyl phosphate and acetate. A pentose phosphate pathway which converted ribose-5-phosphate to glyceraldehyde-3-phosphate was also present. Acetaldehyde could not be formed via the hexose monophosphate shunt or by direct decarboxylation of pyruvate, as the enzymes phosphoketolase and alpha-carboxylase were absent. Phosphoketolase activity was induced in Streptococcus lactis subsp. diacetylactis after growth on D-xylose. Group N streptococci also contained an NAD-dependent alcohol dehydrogenase which reduced acetaldehyde to ethanol while both NAD- and NADP-dependent alcohol dehydrogenase activities were found in Leuconostoc cremoris.", "contents": "Acetaldehyde: an intermediate in the formation of ethanol from glucose by lactic acid bacteria. Group N streptococci formed acetaldehyde and ethanol from glucose. As the enzymes aldehyde dehydrogenase, phosphotransacetylase and acetate kinase were present this would enable these organisms to reduce acetyl-CoA to acetaldehyde and convert acetyl-CoA to acetyl phosphate and acetate. A pentose phosphate pathway which converted ribose-5-phosphate to glyceraldehyde-3-phosphate was also present. Acetaldehyde could not be formed via the hexose monophosphate shunt or by direct decarboxylation of pyruvate, as the enzymes phosphoketolase and alpha-carboxylase were absent. Phosphoketolase activity was induced in Streptococcus lactis subsp. diacetylactis after growth on D-xylose. Group N streptococci also contained an NAD-dependent alcohol dehydrogenase which reduced acetaldehyde to ethanol while both NAD- and NADP-dependent alcohol dehydrogenase activities were found in Leuconostoc cremoris."} {"id": "PMID:177471", "title": "Detection and characterization of differences in plasma corticoid response to treatments.", "content": "Ten experiments involving 3013 observations and 103 animals were studied to characterize variation associated with bovine plasma corticoid concentrations (ng/ml). Total corticoids, corticosterone, or cortisol were measured by competitve protein binding assay. Animals were noncystic or cystic, and measurements were made to establish basal concentrations or to estimate response to stimulation by adrenocorticotrophic hormone injection. Data were analyzed by least squares with the nested model: treatment regimen, animal in treatment, sample in animal in treatment, and sampling time to the highest order of regression (up to seventh) which was statistically significant (P less than .05). Estimates of error variances ranged from .31 for basal cortisol in cystic animals to 233.27 for total corticoids in noncystic, stimulated animals. Coefficients of variation among experiments ranged from 33 to 87% with mean 61%. In most analyses, estimates of experimental error were large indicating need for careful attention to experimental design to insure efficient least-cost experimentation. Use of the power function for nested analysis of variance to accomplish this is demonstrated.", "contents": "Detection and characterization of differences in plasma corticoid response to treatments. Ten experiments involving 3013 observations and 103 animals were studied to characterize variation associated with bovine plasma corticoid concentrations (ng/ml). Total corticoids, corticosterone, or cortisol were measured by competitve protein binding assay. Animals were noncystic or cystic, and measurements were made to establish basal concentrations or to estimate response to stimulation by adrenocorticotrophic hormone injection. Data were analyzed by least squares with the nested model: treatment regimen, animal in treatment, sample in animal in treatment, and sampling time to the highest order of regression (up to seventh) which was statistically significant (P less than .05). Estimates of error variances ranged from .31 for basal cortisol in cystic animals to 233.27 for total corticoids in noncystic, stimulated animals. Coefficients of variation among experiments ranged from 33 to 87% with mean 61%. In most analyses, estimates of experimental error were large indicating need for careful attention to experimental design to insure efficient least-cost experimentation. Use of the power function for nested analysis of variance to accomplish this is demonstrated."} {"id": "PMID:177474", "title": "Growth, pulmonary, and endocrine function in chronic asthma patients on daily and alternate-day adrenocorticosteroid therapy.", "content": "Growth, pulmonary, and adrenal-pituitary function were assessed in 20 steroid-dependent asthmatic children and adolescents while they were on daily prednisone therapy. The patients were then switched to equivalent daily methylprednisolone or twice equivalent alternate-day methylprednisolone for a 3-mo period, after which time studies were repeated. The steroid regimens were then crossed so that those patients taking daily methylprednisolone were switched to alternate-day therapy and the alternate-day therapy patients were switched to daily medication for another 3-mo interval, after which studies were repeated again. Abnormal growth, bone maturation, and cataracts were identified. Mean symptom scores at each evaluation were similar. Pulmonary function tests and shunt studies showed little difference between methylprednisolone and prednisone. Endocrine function tests showed a high incidence of disturbed pituitary and adrenal function. A 3-mo period of alternate-day therapy did not alter this.", "contents": "Growth, pulmonary, and endocrine function in chronic asthma patients on daily and alternate-day adrenocorticosteroid therapy. Growth, pulmonary, and adrenal-pituitary function were assessed in 20 steroid-dependent asthmatic children and adolescents while they were on daily prednisone therapy. The patients were then switched to equivalent daily methylprednisolone or twice equivalent alternate-day methylprednisolone for a 3-mo period, after which time studies were repeated. The steroid regimens were then crossed so that those patients taking daily methylprednisolone were switched to alternate-day therapy and the alternate-day therapy patients were switched to daily medication for another 3-mo interval, after which studies were repeated again. Abnormal growth, bone maturation, and cataracts were identified. Mean symptom scores at each evaluation were similar. Pulmonary function tests and shunt studies showed little difference between methylprednisolone and prednisone. Endocrine function tests showed a high incidence of disturbed pituitary and adrenal function. A 3-mo period of alternate-day therapy did not alter this."} {"id": "PMID:177698", "title": "Peroxidase-conjugate chromatography isolation of conjugates prepared with glutaraldehyde or periodate using polyacrylamide-agarose gel.", "content": "Fractionation abilities of polyacrylamide-agarose gel (Ultrogel) and dextran gel (Sephadex) column chromatography were compared in isolating horseradish peroxidase conjugates, prepared using two different methods. Utrogel AcA-44 provides an efficient separation of monomer conjugated and nonconjugated immunoglobulins resulting from the two-step glutaraldehyde procedure, Sephadex G-200 does not. Both types of columns eluted the polymer conjugates resulting from the periodate procedure in the void volume; these were hardly isolated from the small amount of monomer conjugate. Unreacted horseradish peroxidase, present in very low quantities after the efficient periodate method and in large amounts after the glutaraldehyde procedure, was separated by both gel types.", "contents": "Peroxidase-conjugate chromatography isolation of conjugates prepared with glutaraldehyde or periodate using polyacrylamide-agarose gel. Fractionation abilities of polyacrylamide-agarose gel (Ultrogel) and dextran gel (Sephadex) column chromatography were compared in isolating horseradish peroxidase conjugates, prepared using two different methods. Utrogel AcA-44 provides an efficient separation of monomer conjugated and nonconjugated immunoglobulins resulting from the two-step glutaraldehyde procedure, Sephadex G-200 does not. Both types of columns eluted the polymer conjugates resulting from the periodate procedure in the void volume; these were hardly isolated from the small amount of monomer conjugate. Unreacted horseradish peroxidase, present in very low quantities after the efficient periodate method and in large amounts after the glutaraldehyde procedure, was separated by both gel types."} {"id": "PMID:177699", "title": "Characteristics of a virus causing a pox disease in sheep and goats in Kenya, with observation on the epidemiology and control.", "content": "The sheep and goat pox viruses isolated in Kenya are not host specific as in the Middle East and India. The virus strains from one species are of a similar pathogenicity for the other, and the same virus appears to occur in the field outbreaks in mixed flocks. A silent infection with no skin lesions occurs in the field outbreaks. The virus grows well in lamb testis cell cultures, it does not haemadsorb nor haemagglutinate and is ether sensitive. Most strains could not readily be adapted to grow on the chorioallantoic membrane of embryonated eggs; one isolation only was made in this way. Staining of the virus inclusions showed that they were of DNA; the virus resembled that of lumpy skin disease in many characteristics. It was possible to cross-protect both species with virus of sheep or goat origin. A vaccine was made from tissue culture virus adsorped onto aluminium hydroxide gel and treated with formalin.", "contents": "Characteristics of a virus causing a pox disease in sheep and goats in Kenya, with observation on the epidemiology and control. The sheep and goat pox viruses isolated in Kenya are not host specific as in the Middle East and India. The virus strains from one species are of a similar pathogenicity for the other, and the same virus appears to occur in the field outbreaks in mixed flocks. A silent infection with no skin lesions occurs in the field outbreaks. The virus grows well in lamb testis cell cultures, it does not haemadsorb nor haemagglutinate and is ether sensitive. Most strains could not readily be adapted to grow on the chorioallantoic membrane of embryonated eggs; one isolation only was made in this way. Staining of the virus inclusions showed that they were of DNA; the virus resembled that of lumpy skin disease in many characteristics. It was possible to cross-protect both species with virus of sheep or goat origin. A vaccine was made from tissue culture virus adsorped onto aluminium hydroxide gel and treated with formalin."} {"id": "PMID:177700", "title": "The response to oral poliovaccine in persons aged 16-18 years.", "content": "Serum neutralizing antibodies to polioviruses were titrated in serum samples from 182 police cadets aged 16-18 years before and, in 168 of the cadets, 6 weeks after vaccination with a single dose of oral polio vaccine (OPV). Faecal excretion of poliovirus was also followed. Vaccination histories were obtained and confirmed whenever possible. Pre-vaccination antibody could not be detected against type 1 in 9-3% cadets, against type 2 in 2-7% and against type 3 in 7-7%. Absence of antibody to at least one virus type was found in 14-3% of the cadets. In 93 cadets in whom vaccination histories could be confirmed 40 had received only inactivated polio vaccine (IPV) previously; of these 23% lacked antibody to at least one virus type, and they had less intestinal immunity to a challenge dose of OPV than those previously given OPV. Only two of the cadets known to have had OPV were non-immune - both had received a single dose following full courses of IPV. However, cadets who had received OPV had their last dose of vaccine more recently (average 4-6 years) than those who had received only IPV (all 12 years or more). The serum antibody response to a single booster dose of OPV, and the faecal excretion of each type of virus after vaccination, showed an inverse relation to the corresponding pre-vaccination antibody concentration. A single dose of OPV did not reliably boost the immunity of those who possessed adequate immunity, and a failure to respond was also observed in a proportion of the cadets with no detectable antibody, mostly in the case of type 3 antibody and particularly if antibody to types 1 or 2 virus was also absent. No evidence was obtained that intestinal immunity could be expected in the absence of detectable circulating antibody. The reasons for the absence of a serological response to OPV in some subjects are discussed and consideration is given to the practical significance of the findings. It is suggested that reinforcement of polio immunity at school-leaving is important, particularly at the present time when many of those aged 16-18 years will have been vaccinated only with IPV. A single dose of OPV is not ideal for this purpose, not only because a small proportion of persons are liable to be left unprotected, but also because failure to produce a reliable boost in persons with adequate immunity at the time of vaccination gives rise to the possibility that they may become susceptible later in adult life.", "contents": "The response to oral poliovaccine in persons aged 16-18 years. Serum neutralizing antibodies to polioviruses were titrated in serum samples from 182 police cadets aged 16-18 years before and, in 168 of the cadets, 6 weeks after vaccination with a single dose of oral polio vaccine (OPV). Faecal excretion of poliovirus was also followed. Vaccination histories were obtained and confirmed whenever possible. Pre-vaccination antibody could not be detected against type 1 in 9-3% cadets, against type 2 in 2-7% and against type 3 in 7-7%. Absence of antibody to at least one virus type was found in 14-3% of the cadets. In 93 cadets in whom vaccination histories could be confirmed 40 had received only inactivated polio vaccine (IPV) previously; of these 23% lacked antibody to at least one virus type, and they had less intestinal immunity to a challenge dose of OPV than those previously given OPV. Only two of the cadets known to have had OPV were non-immune - both had received a single dose following full courses of IPV. However, cadets who had received OPV had their last dose of vaccine more recently (average 4-6 years) than those who had received only IPV (all 12 years or more). The serum antibody response to a single booster dose of OPV, and the faecal excretion of each type of virus after vaccination, showed an inverse relation to the corresponding pre-vaccination antibody concentration. A single dose of OPV did not reliably boost the immunity of those who possessed adequate immunity, and a failure to respond was also observed in a proportion of the cadets with no detectable antibody, mostly in the case of type 3 antibody and particularly if antibody to types 1 or 2 virus was also absent. No evidence was obtained that intestinal immunity could be expected in the absence of detectable circulating antibody. The reasons for the absence of a serological response to OPV in some subjects are discussed and consideration is given to the practical significance of the findings. It is suggested that reinforcement of polio immunity at school-leaving is important, particularly at the present time when many of those aged 16-18 years will have been vaccinated only with IPV. A single dose of OPV is not ideal for this purpose, not only because a small proportion of persons are liable to be left unprotected, but also because failure to produce a reliable boost in persons with adequate immunity at the time of vaccination gives rise to the possibility that they may become susceptible later in adult life."} {"id": "PMID:177701", "title": "Mouse or man? Which are pertussis vaccines to protect?", "content": "Type 1 strains of Bordetella pertussis can infect mouse brain and have been recovered as type 1 organisms after death. When introduced into the naso-pharynx of the marmoset, they immediately acquired agglutinogen 2 or 3, and the resulting type 1,2 or 1,3 infection persisted for many weeks. As in the child, agglutinogens 2 and/or 3 appear to be essential for infection of the marmoset, whereas they are quite unnecessary in mouse brain. A vaccine (extract or whole cell) containing agglutinogen 1 may be sufficient to pass the mouse protection test but it may fail to immunize children. The mouse test is inadequate even for the screening of such extracts.", "contents": "Mouse or man? Which are pertussis vaccines to protect? Type 1 strains of Bordetella pertussis can infect mouse brain and have been recovered as type 1 organisms after death. When introduced into the naso-pharynx of the marmoset, they immediately acquired agglutinogen 2 or 3, and the resulting type 1,2 or 1,3 infection persisted for many weeks. As in the child, agglutinogens 2 and/or 3 appear to be essential for infection of the marmoset, whereas they are quite unnecessary in mouse brain. A vaccine (extract or whole cell) containing agglutinogen 1 may be sufficient to pass the mouse protection test but it may fail to immunize children. The mouse test is inadequate even for the screening of such extracts."} {"id": "PMID:177702", "title": "The importance of agglutinin production in mice in the determination of the definitive serotype of Bordetella pertussis.", "content": "A schedule for the routine serotyping of strains of Bordetella pertussis based on agglutinin production in mice to the K-antigens has been worked out. Mice have been found as satisfactory as rabbits but far more economical for the production of the very small volumes of serum which are required. Agglutinin production, used in conjunction with direct agglutination, provides definitive information about serotype.", "contents": "The importance of agglutinin production in mice in the determination of the definitive serotype of Bordetella pertussis. A schedule for the routine serotyping of strains of Bordetella pertussis based on agglutinin production in mice to the K-antigens has been worked out. Mice have been found as satisfactory as rabbits but far more economical for the production of the very small volumes of serum which are required. Agglutinin production, used in conjunction with direct agglutination, provides definitive information about serotype."} {"id": "PMID:177703", "title": "The serotypes of Bordetella pertussis isolated in Great Britain between 1941 and 1968 and a comparison with the serotypes observed in other countries over this period.", "content": "Classification, by agglutinogens, of 634 isolates of Bordetella pertussis collected from 1971 to 1968 in Great Britain demonstrated that a change from a predominantly 1,2,0,4 serotype (75% of those examined during 1941-4) to a predominantly 1,0,3,0 serotype (73% of those examined during 1966-8) occurred sometime after 1953. Furthermore, evidence from the examination of isolates collected between 1941 and 1953 suggests that the change may have been gradual. Isolates of serotype 1,2,3,4 made up 20-30% of the total of our cross-country selection for the periods 1941-4, 1946-9, 1950-3 and 1966-8, but over shorter periods in individual areas the percentage varied from negligible to as high as half of those isolated. Results from other countries show a similar drift towards a 1,0,3 sertype but more often from a 1,2,3 than from 1,2,0 serotype. The value, in epidemiological studies, of extended information obtained by monospecific typing sera to all six, rather than only two or three agglutinogens, and confirmation of the results by agglutinin production is demonstrated: for instance not all 1,0,3 isolates were identical.", "contents": "The serotypes of Bordetella pertussis isolated in Great Britain between 1941 and 1968 and a comparison with the serotypes observed in other countries over this period. Classification, by agglutinogens, of 634 isolates of Bordetella pertussis collected from 1971 to 1968 in Great Britain demonstrated that a change from a predominantly 1,2,0,4 serotype (75% of those examined during 1941-4) to a predominantly 1,0,3,0 serotype (73% of those examined during 1966-8) occurred sometime after 1953. Furthermore, evidence from the examination of isolates collected between 1941 and 1953 suggests that the change may have been gradual. Isolates of serotype 1,2,3,4 made up 20-30% of the total of our cross-country selection for the periods 1941-4, 1946-9, 1950-3 and 1966-8, but over shorter periods in individual areas the percentage varied from negligible to as high as half of those isolated. Results from other countries show a similar drift towards a 1,0,3 sertype but more often from a 1,2,3 than from 1,2,0 serotype. The value, in epidemiological studies, of extended information obtained by monospecific typing sera to all six, rather than only two or three agglutinogens, and confirmation of the results by agglutinin production is demonstrated: for instance not all 1,0,3 isolates were identical."} {"id": "PMID:177704", "title": "The stability of the serotypes of Bordetella pertussis with particular reference to serotype 1,2,3,4.", "content": "Strains of Bordetella pertussis in which all the organisms contain agglutinogens 1 and 3 or 1,2 and 4 are easy to identify as serotypes 1,0,3,0 and 1,2,0,4 respectively; and similarly, stable strains of serotype 1,0,3,4 are occasionally found. During repeated subcultures, passage in vivo, and lyophilization and preservation for many years, these serotypes do not change. Mixing 1,0,3,0 and 1,2,0,4 serotypes and culturing them together in vivo and in vitro produces cultures from which organisms of the same two serotypes can be isolated. In contrast, strains which type as 1,2,3,4 are often a heterogeneous group. We have attempted to classify these as \"stable\", \"variable\" and \"mixed\" cultures. Some strains comprise organisms all of which contain the four agglutinogens and are as easy to type as the strains described above. These we have called \"stable\" 1,2,3,4 strains. Other 1,2,3,4 strains are made up of colonies possessing all four agglutinogens, as shown by agglutinin production, but in amounts varying from day to day so that direct typing is inconsistent. These we have called \"variable\" 1,2,3,4 strains. The last category, \"mixed\", is made up of organisms most of which give rise to stable 1,2,3,4 cultures; a few of the component organisms, however, have one or two of the four agglutinogens missing. The importance of the \"variable\" cultures is emphasized for work on apparent change of serotype, e.g. during infection.", "contents": "The stability of the serotypes of Bordetella pertussis with particular reference to serotype 1,2,3,4. Strains of Bordetella pertussis in which all the organisms contain agglutinogens 1 and 3 or 1,2 and 4 are easy to identify as serotypes 1,0,3,0 and 1,2,0,4 respectively; and similarly, stable strains of serotype 1,0,3,4 are occasionally found. During repeated subcultures, passage in vivo, and lyophilization and preservation for many years, these serotypes do not change. Mixing 1,0,3,0 and 1,2,0,4 serotypes and culturing them together in vivo and in vitro produces cultures from which organisms of the same two serotypes can be isolated. In contrast, strains which type as 1,2,3,4 are often a heterogeneous group. We have attempted to classify these as \"stable\", \"variable\" and \"mixed\" cultures. Some strains comprise organisms all of which contain the four agglutinogens and are as easy to type as the strains described above. These we have called \"stable\" 1,2,3,4 strains. Other 1,2,3,4 strains are made up of colonies possessing all four agglutinogens, as shown by agglutinin production, but in amounts varying from day to day so that direct typing is inconsistent. These we have called \"variable\" 1,2,3,4 strains. The last category, \"mixed\", is made up of organisms most of which give rise to stable 1,2,3,4 cultures; a few of the component organisms, however, have one or two of the four agglutinogens missing. The importance of the \"variable\" cultures is emphasized for work on apparent change of serotype, e.g. during infection."} {"id": "PMID:177705", "title": "Indirect haemagglutination reaction (LH)-the method of choice for the detection of anamnestic antibodies to varicella - zoster (VZ) virus.", "content": "The method of indirect haemagglutination is a sensitive quantitative serological reaction for the detection of anamnestic titres of VZ antibodies. The curve obtained by the examination of a representative population sample has shown that the occurrence of VZ antibodies increases with the age so that 60% of children of under-school age and 90% of 15-year-old children have antibodies to varicella-zoster virus. In adult age groups, seropositivity ranges between 90--100%. The incidence and level of antibodies are identical in both sexes and do not decrease in old age groups. The mean titre of indirect haemagglutinating antibodies was 1 : 128.", "contents": "Indirect haemagglutination reaction (LH)-the method of choice for the detection of anamnestic antibodies to varicella - zoster (VZ) virus. The method of indirect haemagglutination is a sensitive quantitative serological reaction for the detection of anamnestic titres of VZ antibodies. The curve obtained by the examination of a representative population sample has shown that the occurrence of VZ antibodies increases with the age so that 60% of children of under-school age and 90% of 15-year-old children have antibodies to varicella-zoster virus. In adult age groups, seropositivity ranges between 90--100%. The incidence and level of antibodies are identical in both sexes and do not decrease in old age groups. The mean titre of indirect haemagglutinating antibodies was 1 : 128."} {"id": "PMID:177706", "title": "Localization of antibacterial activity and hydrolytic enzymes in subcellular fractions of rabbit and chicken polymorphonuclear leukocytes.", "content": "Polymorphonuclear leukocytes of rabbits and chickens after homogenization in 0.34 M saccharose or after multiple freezing and thawing were subjected to differential centrifugation at 150, 800, 10 000 and 50 000 X g. In the fractions obtained in this manner, total bactericidal activity as well as the activity of myeloperoxidase (E.C. 1. 11. 1. 7), catalase (E.C. 1.11.1.6), lysozyme (E.C. 3.2.1.17), cathepsin D (E.C. 3.4.4.23) and E, beta-D-glucuronidase (E.C. 3.2.1.31) and acid phosphatase (E.C. 3.1.3.2) were determined. Antibacterial activity was found in all fractions from rabbit leukocytes, but only in the first fraction from chick leukocytes. The fractions from rabbit leukocytes contained all enzymes under study while in the fractions from chicken leukocytes the presence of myeloperoxidase, catalase or cathepsin E could not be demonstrated. The highest bactericidal activity was found in the second obtained from the homogenate or rabbit leukocytes. The highest specific activity of myeloperoxidase and homogenate of rabbit leukocytes. The highest specific activity of myeloperoxidase and the lowest activity of cathepsin D were also demonstrated in this fraction. The addition of pepstatin to rabbit leukocytes before their disintegration resulted in the inhibition of the activity of cathepsin D and E and in an increase in the specific activity of myeloperoxidase as well as in total bactericidal activity in the individual fractions. These results testify that microbicidal mechanisms of phagocytes from individual species may differ and when the structure of lysosomes is damaged, the liberated hydrolytic enzymes may gradually inactivate antibacterial substances.", "contents": "Localization of antibacterial activity and hydrolytic enzymes in subcellular fractions of rabbit and chicken polymorphonuclear leukocytes. Polymorphonuclear leukocytes of rabbits and chickens after homogenization in 0.34 M saccharose or after multiple freezing and thawing were subjected to differential centrifugation at 150, 800, 10 000 and 50 000 X g. In the fractions obtained in this manner, total bactericidal activity as well as the activity of myeloperoxidase (E.C. 1. 11. 1. 7), catalase (E.C. 1.11.1.6), lysozyme (E.C. 3.2.1.17), cathepsin D (E.C. 3.4.4.23) and E, beta-D-glucuronidase (E.C. 3.2.1.31) and acid phosphatase (E.C. 3.1.3.2) were determined. Antibacterial activity was found in all fractions from rabbit leukocytes, but only in the first fraction from chick leukocytes. The fractions from rabbit leukocytes contained all enzymes under study while in the fractions from chicken leukocytes the presence of myeloperoxidase, catalase or cathepsin E could not be demonstrated. The highest bactericidal activity was found in the second obtained from the homogenate or rabbit leukocytes. The highest specific activity of myeloperoxidase and homogenate of rabbit leukocytes. The highest specific activity of myeloperoxidase and the lowest activity of cathepsin D were also demonstrated in this fraction. The addition of pepstatin to rabbit leukocytes before their disintegration resulted in the inhibition of the activity of cathepsin D and E and in an increase in the specific activity of myeloperoxidase as well as in total bactericidal activity in the individual fractions. These results testify that microbicidal mechanisms of phagocytes from individual species may differ and when the structure of lysosomes is damaged, the liberated hydrolytic enzymes may gradually inactivate antibacterial substances."} {"id": "PMID:177709", "title": "Ultrastructural study of lesions induced in rabbit cornea by Herpes Simplex virus types 1 and 2.", "content": "Herpes simplex virus types 1 and 2 were used to infect rabbit corneas (without abrasion), and the resulting lesions were compared by light and electron microscopy. The type 1-induced lesion developed more quickly; the infected epithelial cells underwent a progression of defined morphological changes leading to organelle destruction, cell rounding, and death. Virus particles were abundant in the nuclei and cytoplasm of all types of cell in the epithelium, in intercellular spaces, and on the basement membrane. Occasionally, virus was seen to replicate within stromal fibroblasts. In contrast, type 2, although causing similar changes in the epithelial cells, was relatively inefficient in the production of mature virions. Thus type 2 nucleocapsids were synthesized within nuclei in numbers comparable to those of types 1, but intact cytoplasmic virions were uncommon, apparently because of degradation of type 2 virions in cytoplasmic vesicles or tubules. Extracellular type 2 particles were rarely seen. This finding offers an explanation for the relatively slow development of the type 2-induced lesion, but not for its greater severity. All epithelial cells appeared to be capable of supporting replication of either type of virus.", "contents": "Ultrastructural study of lesions induced in rabbit cornea by Herpes Simplex virus types 1 and 2. Herpes simplex virus types 1 and 2 were used to infect rabbit corneas (without abrasion), and the resulting lesions were compared by light and electron microscopy. The type 1-induced lesion developed more quickly; the infected epithelial cells underwent a progression of defined morphological changes leading to organelle destruction, cell rounding, and death. Virus particles were abundant in the nuclei and cytoplasm of all types of cell in the epithelium, in intercellular spaces, and on the basement membrane. Occasionally, virus was seen to replicate within stromal fibroblasts. In contrast, type 2, although causing similar changes in the epithelial cells, was relatively inefficient in the production of mature virions. Thus type 2 nucleocapsids were synthesized within nuclei in numbers comparable to those of types 1, but intact cytoplasmic virions were uncommon, apparently because of degradation of type 2 virions in cytoplasmic vesicles or tubules. Extracellular type 2 particles were rarely seen. This finding offers an explanation for the relatively slow development of the type 2-induced lesion, but not for its greater severity. All epithelial cells appeared to be capable of supporting replication of either type of virus."} {"id": "PMID:177710", "title": "Cytomegalovirus infection in patients receiving immunosuppressive therapy for rheumatologic disorders.", "content": "Evidence of cytomegalovirus infection was sought in 131 patients attending a rheumatology clinic, 211 blood donors, and 14 patients before and after the initiation of cytotoxic immunosuppressive therapy for a rheumatologic condition. The titer of complement-fixing antibody to cytomegalovirus was significantly related to age and sex, but not to rheumatologic disease. After adjustment for age and sex differences, the proportion of patients treated with corticosteroids who had measurable antibody was lower than that of controls (P less than 0.025). Immunosuppressive therapy with azathioprine or cyclophosphamide did not affect the proportion of patients with antibody, but there was a significantly increased titer of antibody in those who were seropositive (P = 0.04). Cytomegalovirus was isolated from the urine of 20% of patients receiving cytotoxic immunosuppressive drugs, but not from any of the patients receiving corticosteroids or neither form of therapy (P = 0.001). Eight of 14 patients followed prospectively after the initiation of therapy with immunosuppressive drugs became infected with cytomegalovirus as demonstrated by a fourfold or greater rise in complement-fixing titer, viruria, or both. Seven of the eight patients were seropositive before therapy, a finding suggesting that immunosuppression acts largely by reactivating latent infection. It is postulated that immunosuppressive agents alone may account for a large proportion of cytomegalovirus infections seen after allograft transplantation.", "contents": "Cytomegalovirus infection in patients receiving immunosuppressive therapy for rheumatologic disorders. Evidence of cytomegalovirus infection was sought in 131 patients attending a rheumatology clinic, 211 blood donors, and 14 patients before and after the initiation of cytotoxic immunosuppressive therapy for a rheumatologic condition. The titer of complement-fixing antibody to cytomegalovirus was significantly related to age and sex, but not to rheumatologic disease. After adjustment for age and sex differences, the proportion of patients treated with corticosteroids who had measurable antibody was lower than that of controls (P less than 0.025). Immunosuppressive therapy with azathioprine or cyclophosphamide did not affect the proportion of patients with antibody, but there was a significantly increased titer of antibody in those who were seropositive (P = 0.04). Cytomegalovirus was isolated from the urine of 20% of patients receiving cytotoxic immunosuppressive drugs, but not from any of the patients receiving corticosteroids or neither form of therapy (P = 0.001). Eight of 14 patients followed prospectively after the initiation of therapy with immunosuppressive drugs became infected with cytomegalovirus as demonstrated by a fourfold or greater rise in complement-fixing titer, viruria, or both. Seven of the eight patients were seropositive before therapy, a finding suggesting that immunosuppression acts largely by reactivating latent infection. It is postulated that immunosuppressive agents alone may account for a large proportion of cytomegalovirus infections seen after allograft transplantation."} {"id": "PMID:177712", "title": "Mechanism of injury of virus-infected cells by antiviral antibody and complement: participation of IgG, F(ab')2, and the alternative complement pathway.", "content": "Antibody-mediated C-dependent lysis of cell lines infected with herpes simplex type 1 virus, influenza A degrees virus, measles virus, and mumps virus occurred by the alternative C pathway with the participation of IgG antibodies. Lysis occurred only with immune human sera, Mg++ EGTA immune sera, and immune sera depleted of C4 or treated with Fab anti-C4. Lysis did not occur with nonimmune sera, Mg++ EDTA immune sera, and immune sera heated 50 degrees C for 25 min, depleted of factor B or treated with Fab antifactor B. Lysis was restored to heated and factor B immunodepleted immune sera by addition of factor B, but not by addition of an excess of C2. Further studies showed that lysis of HeLa cells infected with measles virus was induced by both immune IgG and F(ab')2 but not Fab' in the presence of a nonantibody-containing human C source. Lysis of measles virus-infected cells was also indpendent of movement of viral antigens on the surface of the infected cells, as inhibition of viral antigen capping by cytochalasin B or sodium azide was not associated with abrogation of immune lysis.", "contents": "Mechanism of injury of virus-infected cells by antiviral antibody and complement: participation of IgG, F(ab')2, and the alternative complement pathway. Antibody-mediated C-dependent lysis of cell lines infected with herpes simplex type 1 virus, influenza A degrees virus, measles virus, and mumps virus occurred by the alternative C pathway with the participation of IgG antibodies. Lysis occurred only with immune human sera, Mg++ EGTA immune sera, and immune sera depleted of C4 or treated with Fab anti-C4. Lysis did not occur with nonimmune sera, Mg++ EDTA immune sera, and immune sera heated 50 degrees C for 25 min, depleted of factor B or treated with Fab antifactor B. Lysis was restored to heated and factor B immunodepleted immune sera by addition of factor B, but not by addition of an excess of C2. Further studies showed that lysis of HeLa cells infected with measles virus was induced by both immune IgG and F(ab')2 but not Fab' in the presence of a nonantibody-containing human C source. Lysis of measles virus-infected cells was also indpendent of movement of viral antigens on the surface of the infected cells, as inhibition of viral antigen capping by cytochalasin B or sodium azide was not associated with abrogation of immune lysis."} {"id": "PMID:177713", "title": "Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.", "content": "Beta cells were isolated from strains of mice that were susceptible and resistant to encephalomyocarditis (EMC) viral-induced diabetes mellitus. Beta cells from susceptible mice that were infected in vivo with EMC virus showed higher viral titers, more severe degranulation, and lower concentrations of immunoreactive insulin than beta cells from resistant mice. Immunofluorescence and infectious center assays revealed that pancreas from susceptible mice contained at least 10 times more infected cells than pancreas from resistant mice. Beta cell cultures prepared from susceptible mice and infected in vitro also showed higher viral titers and more severe cytopathologic changes than beta cell cultures from resistant mice. In contrast to beta cell cultures, virus replicated equally well in primary embryo and kidney cell cultures from susceptible and resistant strains of mice. It is concluded that the development of EMC virus-induced diabetes is related to genetically determined host differences in the capacity of the virus to infect beta cells.", "contents": "Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells. Beta cells were isolated from strains of mice that were susceptible and resistant to encephalomyocarditis (EMC) viral-induced diabetes mellitus. Beta cells from susceptible mice that were infected in vivo with EMC virus showed higher viral titers, more severe degranulation, and lower concentrations of immunoreactive insulin than beta cells from resistant mice. Immunofluorescence and infectious center assays revealed that pancreas from susceptible mice contained at least 10 times more infected cells than pancreas from resistant mice. Beta cell cultures prepared from susceptible mice and infected in vitro also showed higher viral titers and more severe cytopathologic changes than beta cell cultures from resistant mice. In contrast to beta cell cultures, virus replicated equally well in primary embryo and kidney cell cultures from susceptible and resistant strains of mice. It is concluded that the development of EMC virus-induced diabetes is related to genetically determined host differences in the capacity of the virus to infect beta cells."} {"id": "PMID:177714", "title": "The effects of changing the phase and duration of sleep.", "content": "The relative effects of extended sleep, reduced sleep, and shifts of habitual sleep time on subsequent performance and mood were studied. Ten healthy male university students who regularly sleep 9.5-10.5 hr were the subjects. Measurements were obtained from a 45-min auditory vigilance task, a 5-min experimenter-paced addition task and a mood adjective check list 30 min after awakening, at midday, and in the evening following five electroencephalographically recorded nights of sleep. The experimental treatments compromised at 9.5-10.5 hr habitual sleep condition and four conditions in which the regular sleep period was lengthened, reduced, delayed, and advanced by 3hr. Following each 3-hr altered condition of sleep there was an equivalent decline in vigilance performance and in subjective arousal as measured by the mood scales. Together with other recent evidence, the present results support the hypothesis that acute disruption of the 24-hr sleep-wakefulness cycle produces degradations in human performance largely independent of total sleep time.", "contents": "The effects of changing the phase and duration of sleep. The relative effects of extended sleep, reduced sleep, and shifts of habitual sleep time on subsequent performance and mood were studied. Ten healthy male university students who regularly sleep 9.5-10.5 hr were the subjects. Measurements were obtained from a 45-min auditory vigilance task, a 5-min experimenter-paced addition task and a mood adjective check list 30 min after awakening, at midday, and in the evening following five electroencephalographically recorded nights of sleep. The experimental treatments compromised at 9.5-10.5 hr habitual sleep condition and four conditions in which the regular sleep period was lengthened, reduced, delayed, and advanced by 3hr. Following each 3-hr altered condition of sleep there was an equivalent decline in vigilance performance and in subjective arousal as measured by the mood scales. Together with other recent evidence, the present results support the hypothesis that acute disruption of the 24-hr sleep-wakefulness cycle produces degradations in human performance largely independent of total sleep time."} {"id": "PMID:177715", "title": "Variation in the effects of antidiuretic hormone on the isolated skin of the toad, Scaphiopus couchi.", "content": "The rate of active sodium transport as measured by short-circuit current across the isolated skin of the toad, Scaphiopus couchi, was elevated following vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml) treatment of skins from active animals at all times of the year tested. Skins from dormant animals showed no such elevation at any time of the year. The rate of active sodium transport was elevated following treatment with dibutyryl cyclic AMP (2.5mM) plus theophylline (10 mM) in all skins tested. The hydraulic conductivity of isolated skins from both active and dormant animals showed no significant change following treatment with vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml except on the first day following emergence from dormancy in the field. A correlation was, therefore, observed between the occurrence of a hydroosmotic response to antidiuretic hormones and the seasonal exposure of S. couchi to standing water. A small but significant elevation of hydraulic conductivity was observed across the skins of dormant toads following treatment with dibutyryl cyclic AMP (2.5 mM) plus theophylline (10 mM) whereas a substantial elevation was observed with the skins of active animals.", "contents": "Variation in the effects of antidiuretic hormone on the isolated skin of the toad, Scaphiopus couchi. The rate of active sodium transport as measured by short-circuit current across the isolated skin of the toad, Scaphiopus couchi, was elevated following vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml) treatment of skins from active animals at all times of the year tested. Skins from dormant animals showed no such elevation at any time of the year. The rate of active sodium transport was elevated following treatment with dibutyryl cyclic AMP (2.5mM) plus theophylline (10 mM) in all skins tested. The hydraulic conductivity of isolated skins from both active and dormant animals showed no significant change following treatment with vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml except on the first day following emergence from dormancy in the field. A correlation was, therefore, observed between the occurrence of a hydroosmotic response to antidiuretic hormones and the seasonal exposure of S. couchi to standing water. A small but significant elevation of hydraulic conductivity was observed across the skins of dormant toads following treatment with dibutyryl cyclic AMP (2.5 mM) plus theophylline (10 mM) whereas a substantial elevation was observed with the skins of active animals."} {"id": "PMID:177716", "title": "Forensic archaeology.", "content": "This presentation attempts to demonstrate the value of the use of improved methods in the excavation of buried bodies involved in a criminal investigation. Care in the removal of the skeleton and proper recording will document the interrelationship of all objects found in and around the grave and can, to a certain extent, recreate the event. Carelessness will result in evidence being irretrievably lost. The crime scene investigator's problem, arachaeologically, includes the nature of the remains, dating the time of burial, and techniques of excavation. Archaeological recovery techniques should be adopted in homicide investigation involving buried bodies.", "contents": "Forensic archaeology. This presentation attempts to demonstrate the value of the use of improved methods in the excavation of buried bodies involved in a criminal investigation. Care in the removal of the skeleton and proper recording will document the interrelationship of all objects found in and around the grave and can, to a certain extent, recreate the event. Carelessness will result in evidence being irretrievably lost. The crime scene investigator's problem, arachaeologically, includes the nature of the remains, dating the time of burial, and techniques of excavation. Archaeological recovery techniques should be adopted in homicide investigation involving buried bodies."} {"id": "PMID:177721", "title": "A comparison of molecular weights of foot-and-mouth disease virus RNA fragments determined from lengths and s-rates.", "content": "A comparison was made of the calculated mol. wt. of RNA fragments from foot-and-mouth disease virus (FMDV) types A12 strain 119, C3 Resende and O1 Brugge. The mol. wt. were calculated by two methods: from the measurements of strand lengths in the electron micrographs and from the observed sedimentation rates (s-rates). RNA extracted from virus by dialysis against water usually had three to four prominent strands of different lengths. Mol. wt. calculated from s-rates (and converted to strand lengths) generally agreed with those measured on electron micrographs. Differences which occurred appeared to be attributable to further breakage during processing for electron microscopy. Major fragment strand lengths range from 0-65 to 2-45 mum. The modal lengths of RNA fragments were preparation-dependent, ranging from 1-25 to 1-95 mum for A12 119, 1-05 to 1-75 mum for C3 Resende, and 1-65 to 2-45 mum for O1 Brugge. There was one fragment length 1-95 mum common to all three types of FMDV RNA and several others which appear in at least two types. Calculations using the molar ratios of nucleotide residues in FMDV RNA, a mol. wt. of FMDV RNA of 2-65 X 10(6) and an internucleotide spacing of 3-17 A indicate that intact FMDV RNA should be 2-62 mum long and therefore would contain approx. 8270 nucleotides. The derived mathematical expression for the relationship between mol. wt. (M) and s-rate (S) giving the best fit for all data was M = 1725 S2-07, a result close to that derived by Spirin (1963) for other single-stranded RNAs.", "contents": "A comparison of molecular weights of foot-and-mouth disease virus RNA fragments determined from lengths and s-rates. A comparison was made of the calculated mol. wt. of RNA fragments from foot-and-mouth disease virus (FMDV) types A12 strain 119, C3 Resende and O1 Brugge. The mol. wt. were calculated by two methods: from the measurements of strand lengths in the electron micrographs and from the observed sedimentation rates (s-rates). RNA extracted from virus by dialysis against water usually had three to four prominent strands of different lengths. Mol. wt. calculated from s-rates (and converted to strand lengths) generally agreed with those measured on electron micrographs. Differences which occurred appeared to be attributable to further breakage during processing for electron microscopy. Major fragment strand lengths range from 0-65 to 2-45 mum. The modal lengths of RNA fragments were preparation-dependent, ranging from 1-25 to 1-95 mum for A12 119, 1-05 to 1-75 mum for C3 Resende, and 1-65 to 2-45 mum for O1 Brugge. There was one fragment length 1-95 mum common to all three types of FMDV RNA and several others which appear in at least two types. Calculations using the molar ratios of nucleotide residues in FMDV RNA, a mol. wt. of FMDV RNA of 2-65 X 10(6) and an internucleotide spacing of 3-17 A indicate that intact FMDV RNA should be 2-62 mum long and therefore would contain approx. 8270 nucleotides. The derived mathematical expression for the relationship between mol. wt. (M) and s-rate (S) giving the best fit for all data was M = 1725 S2-07, a result close to that derived by Spirin (1963) for other single-stranded RNAs."} {"id": "PMID:177722", "title": "Deoxyribonucleoside triphosphate pools in herpes simplex type 1 infected cells.", "content": "Deoxyribonucleoside triphosphate pools were analysed in both exponentially growing and serum starved wild type BHK C13 cells and in a derivative of this cell line which lacks both thymidine kinase and deoxycytidine kinase activities, before and after infection with herpes simplex virus. Serum starved BHK cells had low levels of all four deoxyribonucleoside triphosphates. In exponentially growing cells all pools were expanded, the pool of dCTP being largest and dGTP the smallest. The dATP and dTTP pools were of intermediate sizes. In exponentially growing deoxypyrimidine kinase free cells the pools, with respect to level and distribution, were the same as those observed in wild type cells. After infection with herpes simplex virus there were marked changes in the levels of all deoxyribonucleoside triphosphate pools; the most predominant being a 25- to 50-fold expansion of dTTP pool. The pools of dCTP and dGTP also increased while the pool of dATP was very much reduced. These effects could be observed in both wild type and mutant cells.", "contents": "Deoxyribonucleoside triphosphate pools in herpes simplex type 1 infected cells. Deoxyribonucleoside triphosphate pools were analysed in both exponentially growing and serum starved wild type BHK C13 cells and in a derivative of this cell line which lacks both thymidine kinase and deoxycytidine kinase activities, before and after infection with herpes simplex virus. Serum starved BHK cells had low levels of all four deoxyribonucleoside triphosphates. In exponentially growing cells all pools were expanded, the pool of dCTP being largest and dGTP the smallest. The dATP and dTTP pools were of intermediate sizes. In exponentially growing deoxypyrimidine kinase free cells the pools, with respect to level and distribution, were the same as those observed in wild type cells. After infection with herpes simplex virus there were marked changes in the levels of all deoxyribonucleoside triphosphate pools; the most predominant being a 25- to 50-fold expansion of dTTP pool. The pools of dCTP and dGTP also increased while the pool of dATP was very much reduced. These effects could be observed in both wild type and mutant cells."} {"id": "PMID:177723", "title": "Deoxyribonucleoside triphosphate pools in cells infected with deoxypyrimidine kinaseless herpes simplex virus.", "content": "Deoxyribonucleoside triphosphate pools were analysed after infection of cells with mutant herpes simplex virus which lacks the ability to induce the enzyme deoxypyrimidine kinase. After infection of exponentially growing BHK C13 cells, an increase in all four dNTP pools was observed. However, after infection of cells which themselves cannot incorporate exogenous pyrimidine deoxynucleosides only the purine deoxynucleoside triphosphate pools increased in size. In a system which is non-permissive for virus infection, i.e. resting BHK C13 cells which have been infected with dPyK-, HSV-1, there is an increase in all dNTP pool sizes except for dTTP. A comparison of the changes in dNTP pool sizes after infection with either wild type of dPyK- mutant HSV suggests an important role for dTTP in the control of both the production of the other DNA precursors and of viral DNA synthesis.", "contents": "Deoxyribonucleoside triphosphate pools in cells infected with deoxypyrimidine kinaseless herpes simplex virus. Deoxyribonucleoside triphosphate pools were analysed after infection of cells with mutant herpes simplex virus which lacks the ability to induce the enzyme deoxypyrimidine kinase. After infection of exponentially growing BHK C13 cells, an increase in all four dNTP pools was observed. However, after infection of cells which themselves cannot incorporate exogenous pyrimidine deoxynucleosides only the purine deoxynucleoside triphosphate pools increased in size. In a system which is non-permissive for virus infection, i.e. resting BHK C13 cells which have been infected with dPyK-, HSV-1, there is an increase in all dNTP pool sizes except for dTTP. A comparison of the changes in dNTP pool sizes after infection with either wild type of dPyK- mutant HSV suggests an important role for dTTP in the control of both the production of the other DNA precursors and of viral DNA synthesis."} {"id": "PMID:177724", "title": "The effect of tilorone hydrochloride on the growth of several animal viruses in tissue cultures.", "content": "Tilorone hydrochloride, at a concentration of 10 mug/ml inhibits the growth of herpes simplex virus type 1 in BS-C-1 cells. The growth of vaccinia virus in BS-C-1 cells is partially inhibited; however, six viruses containing RNA, including four members of the togavirus group grown in chick fibroblasts, are not affected by the drug. The inhibition of the growth of herpes virus by tilorone hydrochloride is greater when the multiplicity of infection is lower than 1 p.f.u/cell and when the drug is added early in the course of infection.", "contents": "The effect of tilorone hydrochloride on the growth of several animal viruses in tissue cultures. Tilorone hydrochloride, at a concentration of 10 mug/ml inhibits the growth of herpes simplex virus type 1 in BS-C-1 cells. The growth of vaccinia virus in BS-C-1 cells is partially inhibited; however, six viruses containing RNA, including four members of the togavirus group grown in chick fibroblasts, are not affected by the drug. The inhibition of the growth of herpes virus by tilorone hydrochloride is greater when the multiplicity of infection is lower than 1 p.f.u/cell and when the drug is added early in the course of infection."} {"id": "PMID:177725", "title": "Inhibition of protein synthesis in reticulocyte lysates by poliovirus.", "content": "Addition of 1 X 10(10) p.f.u. purified poliovirus to 100 mul of a rabbit reticulocyte lysate protein synthesizing system causes a complete inhibition of initiation of protein synthesis. This inhibition is not due to the viral RNA nor to any contaminants of the preparation, but is most likely caused by the viral coat protein.", "contents": "Inhibition of protein synthesis in reticulocyte lysates by poliovirus. Addition of 1 X 10(10) p.f.u. purified poliovirus to 100 mul of a rabbit reticulocyte lysate protein synthesizing system causes a complete inhibition of initiation of protein synthesis. This inhibition is not due to the viral RNA nor to any contaminants of the preparation, but is most likely caused by the viral coat protein."} {"id": "PMID:177726", "title": "An improved assay for feline leukaemia virus pseudotypes of murine sarcoma virus.", "content": "An assay is described for feline leukaemia virus pseudotypes of murine sarcoma virus which increased the virus titre by about 100-fold over conventional assays. The titre is independent of dilution and no secondary focus formation occurs. The assay may be used to study virus neutralization and to detect and type feline leukaemia virus in feline embryo cells by interference.", "contents": "An improved assay for feline leukaemia virus pseudotypes of murine sarcoma virus. An assay is described for feline leukaemia virus pseudotypes of murine sarcoma virus which increased the virus titre by about 100-fold over conventional assays. The titre is independent of dilution and no secondary focus formation occurs. The assay may be used to study virus neutralization and to detect and type feline leukaemia virus in feline embryo cells by interference."} {"id": "PMID:177727", "title": "Mutants of herpes simplex virus types 1 and 2 that are resistant to phosphonoacetic acid induce altered DNA polymerase activities in infected cells.", "content": "Three mutants of herpes simplex virus (HSV) have been isolated which form plaques in the presence of 100 mug/ml phosphonoacetic acid (PPA). All three mutants (3 from HSV-1 strain 17 syn+, 14 from HSV-1 strain 17 syn, and 19 from HSV-2) induce viral DNA synthesis and viral DNA polymerase activity, and these are much less sensitive to PPA than the wild-type virus. The results support the hypothesis that PPA interacts directly with the viral DNA polymerase protein, at least part of which is virus coded.", "contents": "Mutants of herpes simplex virus types 1 and 2 that are resistant to phosphonoacetic acid induce altered DNA polymerase activities in infected cells. Three mutants of herpes simplex virus (HSV) have been isolated which form plaques in the presence of 100 mug/ml phosphonoacetic acid (PPA). All three mutants (3 from HSV-1 strain 17 syn+, 14 from HSV-1 strain 17 syn, and 19 from HSV-2) induce viral DNA synthesis and viral DNA polymerase activity, and these are much less sensitive to PPA than the wild-type virus. The results support the hypothesis that PPA interacts directly with the viral DNA polymerase protein, at least part of which is virus coded."} {"id": "PMID:177728", "title": "Characterization of the minor polypeptides in the foot-and-mouth disease particle.", "content": "In addition to the four major polypeptides VP1 and VP4, foot-and-mouth disease virus particles contain two minor polypeptides, mol. wt. 40 X 10(3) (P40) and 52 X 10(3) (P52). Extensive purification procedures failed to remove these minor polypeptides from the virus particles. Polypeptide P40 co-electrophoresed in SDS-polyacrylamide gels with VP0, the probable precursor of VP2 and VP4 and was inaccessible to iodination in situ. The second minor polypeptide, P52, co-electrophoresed with the virus infection associated (VIA) antigen found in large amounts in harvests of the virus grown in BHK 21 cells. Polypeptide P52 was shown to be located near the surface of the virus particle by iodination experiments and by its removal on incubating the particles with trypsin or chymotrypsin. Pactamycin mapping showed that this polypeptide was not a precursor of the structural polypeptides. About one copy of P52 and 4 copies of P40 were found in the virus particles sedimenting at 146S. However a larger number of copies was found in those virus particles sedimenting faster than the 146S peak.", "contents": "Characterization of the minor polypeptides in the foot-and-mouth disease particle. In addition to the four major polypeptides VP1 and VP4, foot-and-mouth disease virus particles contain two minor polypeptides, mol. wt. 40 X 10(3) (P40) and 52 X 10(3) (P52). Extensive purification procedures failed to remove these minor polypeptides from the virus particles. Polypeptide P40 co-electrophoresed in SDS-polyacrylamide gels with VP0, the probable precursor of VP2 and VP4 and was inaccessible to iodination in situ. The second minor polypeptide, P52, co-electrophoresed with the virus infection associated (VIA) antigen found in large amounts in harvests of the virus grown in BHK 21 cells. Polypeptide P52 was shown to be located near the surface of the virus particle by iodination experiments and by its removal on incubating the particles with trypsin or chymotrypsin. Pactamycin mapping showed that this polypeptide was not a precursor of the structural polypeptides. About one copy of P52 and 4 copies of P40 were found in the virus particles sedimenting at 146S. However a larger number of copies was found in those virus particles sedimenting faster than the 146S peak."} {"id": "PMID:177729", "title": "Effect of ammonium 5-tungsto-2-antimoniate on encephalomyocarditis and vesicular stomatitis virus infections in mice.", "content": "Ammonium 5-tungsto-2-antimoniate (HPA 23) protected micr partially or completely against two strains of encephalomyocarditis (EMC) virus and one strain of vesicular stomatitis (VSV) virus. The best protective effect was obtained with EMC strain VR 129 and VSV when a single i.p. injection of HPA 23 was administered shortly before virus inoculation. Mice protected by HPA 23 against EMC strain VR129 had virus titres in the blood and brain similar to those in untreated mice. A synergism between interferon and HPA 23 was observed in mice infected with EMC VR129. Our results demonstrate the in vivo activity of HPA 23 against two lethal viral infections and suggest that, at least in mice infected with EMC, death may not be related solely to virus multiplication.", "contents": "Effect of ammonium 5-tungsto-2-antimoniate on encephalomyocarditis and vesicular stomatitis virus infections in mice. Ammonium 5-tungsto-2-antimoniate (HPA 23) protected micr partially or completely against two strains of encephalomyocarditis (EMC) virus and one strain of vesicular stomatitis (VSV) virus. The best protective effect was obtained with EMC strain VR 129 and VSV when a single i.p. injection of HPA 23 was administered shortly before virus inoculation. Mice protected by HPA 23 against EMC strain VR129 had virus titres in the blood and brain similar to those in untreated mice. A synergism between interferon and HPA 23 was observed in mice infected with EMC VR129. Our results demonstrate the in vivo activity of HPA 23 against two lethal viral infections and suggest that, at least in mice infected with EMC, death may not be related solely to virus multiplication."} {"id": "PMID:177730", "title": "Herpesvirus proteins: DNA polymerase and pyrimidine deoxynucleoside kinase activities in temperature-sensitive mutants of herpes simplex virus type 2.", "content": "Eleven temperature-sensitive mutants of herpes simplex virus type 2 strain HG52 were examined for ability to induce DNA polymerase activity in BHK 21/C13 cells. All mutants induced DNA polymerase at a permissive temperature, (31 degrees C) and all DNA-positive mutants at a non-permissive temperature (38 degrees C). Three DNA-negative mutants induced no DNA polymerase (ts 6, ts 9) or very little DNA polymerase (ts 11), at a non-permissive temperature, while ts 1, also DNA negative, induced a little more DNA polymerase than wild-type, often at both temperatures. The DNA polymerase induced by ts 6 at 31 degrees C was temperature-sensitive in vivo, but only slightly so in vitro. These results were confirmed immunologically and suggest that HSV-2 codes for at least part of a DNA polymerase activity, necessary for infection, and that full expression of this enzyme involves at least three viral genes.", "contents": "Herpesvirus proteins: DNA polymerase and pyrimidine deoxynucleoside kinase activities in temperature-sensitive mutants of herpes simplex virus type 2. Eleven temperature-sensitive mutants of herpes simplex virus type 2 strain HG52 were examined for ability to induce DNA polymerase activity in BHK 21/C13 cells. All mutants induced DNA polymerase at a permissive temperature, (31 degrees C) and all DNA-positive mutants at a non-permissive temperature (38 degrees C). Three DNA-negative mutants induced no DNA polymerase (ts 6, ts 9) or very little DNA polymerase (ts 11), at a non-permissive temperature, while ts 1, also DNA negative, induced a little more DNA polymerase than wild-type, often at both temperatures. The DNA polymerase induced by ts 6 at 31 degrees C was temperature-sensitive in vivo, but only slightly so in vitro. These results were confirmed immunologically and suggest that HSV-2 codes for at least part of a DNA polymerase activity, necessary for infection, and that full expression of this enzyme involves at least three viral genes."} {"id": "PMID:177731", "title": "Latent herpetic infections following experimental viraemia.", "content": "The spectrum of tissues harbouring latent herpes simplex virus following intravenous inoculation of mice was defined by in vitro co-cultivation techniques. The virus could be detected in central and peripheral nervous systems (including adrenal medulla), but could not be found in any non-neural tissues. Spinal ganglia were the organs most commonly involved. The relationship of these findings to the natural history of herpetic infections is discussed.", "contents": "Latent herpetic infections following experimental viraemia. The spectrum of tissues harbouring latent herpes simplex virus following intravenous inoculation of mice was defined by in vitro co-cultivation techniques. The virus could be detected in central and peripheral nervous systems (including adrenal medulla), but could not be found in any non-neural tissues. Spinal ganglia were the organs most commonly involved. The relationship of these findings to the natural history of herpetic infections is discussed."} {"id": "PMID:177732", "title": "Purification of equine herpesvirus type 1.", "content": "A method for the purification of enveloped infectious equine herpesvirus type 1 (EHV-1) is presented. Virus from cell culture fluids harvested at 48 h post infection was concentrated by sedimentation and partially purified by differential precipitation with ammonium sulphate. The final steps of purification consisted of two cycles of flotation of virus in pre-formed CsCl density gradients. Yields of infectious virus were about 30% (18 to 44%) of that present in starting material. As judged by electron microscopy, mixed radioisotope labelling, and absence of phosphohydrolase, virus preparations possessed a high degree of purity. Sedimentation of EHV-1 into CsCl density gradients resulted in low recovery of infectious virus. Flotation of virus in CsCl gradients, however, was not deleterious to infectivity of viral preparations.", "contents": "Purification of equine herpesvirus type 1. A method for the purification of enveloped infectious equine herpesvirus type 1 (EHV-1) is presented. Virus from cell culture fluids harvested at 48 h post infection was concentrated by sedimentation and partially purified by differential precipitation with ammonium sulphate. The final steps of purification consisted of two cycles of flotation of virus in pre-formed CsCl density gradients. Yields of infectious virus were about 30% (18 to 44%) of that present in starting material. As judged by electron microscopy, mixed radioisotope labelling, and absence of phosphohydrolase, virus preparations possessed a high degree of purity. Sedimentation of EHV-1 into CsCl density gradients resulted in low recovery of infectious virus. Flotation of virus in CsCl gradients, however, was not deleterious to infectivity of viral preparations."} {"id": "PMID:177733", "title": "EEG findings, rapid ACTH test and autonomic nervous symptoms in patients with alopecia areata.", "content": "Patients of multiple alopecia areata were examined in their EEG findings and rapid ACTH test and described the symptoms concerning the neuroautonomic system. Some abnormal EEG findings were seen in 75 cases out of the examined 105 patients. As to the rapid ACTH test, 10 cases out of 45 subjects were abnormal. A positive correlation was considered between abnormal EEG findings and abnormal value in the rapid ACTH test. It is speculated that the regulation centers in the brainstem and hypothalamus play a great role in pathophysiology of multiple areata.", "contents": "EEG findings, rapid ACTH test and autonomic nervous symptoms in patients with alopecia areata. Patients of multiple alopecia areata were examined in their EEG findings and rapid ACTH test and described the symptoms concerning the neuroautonomic system. Some abnormal EEG findings were seen in 75 cases out of the examined 105 patients. As to the rapid ACTH test, 10 cases out of 45 subjects were abnormal. A positive correlation was considered between abnormal EEG findings and abnormal value in the rapid ACTH test. It is speculated that the regulation centers in the brainstem and hypothalamus play a great role in pathophysiology of multiple areata."} {"id": "PMID:177737", "title": "Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy.", "content": "Two cases are reported of progressive trigeminal neutopathy with nasal ulceration. One patient developed signs of spinal cord involvement 15 years after the onset of trigeminal symptoms and died after a total course of 21 years. Necropsy revealed an unusual trigeminospinal system degeneration with deposition of amyloid-like substances in the affected structures. The other patient is alive eight years after the onset of symptoms, the only indication of a lesion outside the trigeminal nerve being a patch of numbness in one leg.", "contents": "Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy. Two cases are reported of progressive trigeminal neutopathy with nasal ulceration. One patient developed signs of spinal cord involvement 15 years after the onset of trigeminal symptoms and died after a total course of 21 years. Necropsy revealed an unusual trigeminospinal system degeneration with deposition of amyloid-like substances in the affected structures. The other patient is alive eight years after the onset of symptoms, the only indication of a lesion outside the trigeminal nerve being a patch of numbness in one leg."} {"id": "PMID:177738", "title": "The reinnervated motor unit in man. A single fibre EMG multielectrode investigation.", "content": "Motor units in patients with motor neurone disease and polyneuropathy were studied with a new multielectrode technique allowing fibre mapping. In these disorders which are characterised by reinnervation the motor unit fibre distribution is changed from a normal scattered pattern to grouping often in clinically uninvolved muscles without definite EMG abnormalities. The changes found with this multielectrode technique in man are in accordance with those found in reinnervated motor units studied histochemically in the experimental animal.", "contents": "The reinnervated motor unit in man. A single fibre EMG multielectrode investigation. Motor units in patients with motor neurone disease and polyneuropathy were studied with a new multielectrode technique allowing fibre mapping. In these disorders which are characterised by reinnervation the motor unit fibre distribution is changed from a normal scattered pattern to grouping often in clinically uninvolved muscles without definite EMG abnormalities. The changes found with this multielectrode technique in man are in accordance with those found in reinnervated motor units studied histochemically in the experimental animal."} {"id": "PMID:177739", "title": "\"Satellite potentials\" and the duration of motor unit potentials in normal, neuropathic and myopathic muscles.", "content": "Time-locked activity in the EMG was studied in normal, neuropathic and myopathic muscles, using the averaging technique. Normal and neuropathic muscles seemed in most cases not to differ with regard to the frequency nor the quality of \"satellite signals\", i.e. small and short potentials joining the main component of the MUP with a constant interval, up to 26 ms in duration. In normal muscles 10% of the MUPs and in neuropathic muscles 12% had a satellite, which, when studied, showed no signs of blocking. However, in 2 patients with an apparent old spinal affection both an increased number and an increased latency of satellite signals were found. In the different myopathies studied 45% of the MUPs recorded consecutively were preceded or followed by an often increased number of tiny satellites. Sometimes the satellites joining the myopathic MUP formed a long (up to 60 ms) \"tail\" after the triggering component. On the basis of our results we conclude that in myopathies the total duration of MUPs is in certain cases pathologically incrased rather than decreased.", "contents": "\"Satellite potentials\" and the duration of motor unit potentials in normal, neuropathic and myopathic muscles. Time-locked activity in the EMG was studied in normal, neuropathic and myopathic muscles, using the averaging technique. Normal and neuropathic muscles seemed in most cases not to differ with regard to the frequency nor the quality of \"satellite signals\", i.e. small and short potentials joining the main component of the MUP with a constant interval, up to 26 ms in duration. In normal muscles 10% of the MUPs and in neuropathic muscles 12% had a satellite, which, when studied, showed no signs of blocking. However, in 2 patients with an apparent old spinal affection both an increased number and an increased latency of satellite signals were found. In the different myopathies studied 45% of the MUPs recorded consecutively were preceded or followed by an often increased number of tiny satellites. Sometimes the satellites joining the myopathic MUP formed a long (up to 60 ms) \"tail\" after the triggering component. On the basis of our results we conclude that in myopathies the total duration of MUPs is in certain cases pathologically incrased rather than decreased."} {"id": "PMID:177741", "title": "Double-tracer scintigraphy with 67Ga-citrate and 99mTc-sulfur colloid in the diagnosis of hepatic tumors.", "content": "A method of liver scanning based on a subtraction technique with simultaneous use of two tracers, 67Ga-citrate and 99mTc-sulfur colloid, is described. The subtraction technique isolates radiogallium uptake by the space-occupying hepatic lesions by subtracting interference due to tracer uptake by healthy hepatic tissue. In 82 patients, the method yielded a correct result in 94.7% of the positive scans and in 97.7% of the negatives. Two false positives and one false negative occurred. Very poor results were obtained in the same patients using conventional technetium and gallium scans: only 20.7% of these interpretations were correct. The method proved very helpful in differentiating malignant from benign lesions.", "contents": "Double-tracer scintigraphy with 67Ga-citrate and 99mTc-sulfur colloid in the diagnosis of hepatic tumors. A method of liver scanning based on a subtraction technique with simultaneous use of two tracers, 67Ga-citrate and 99mTc-sulfur colloid, is described. The subtraction technique isolates radiogallium uptake by the space-occupying hepatic lesions by subtracting interference due to tracer uptake by healthy hepatic tissue. In 82 patients, the method yielded a correct result in 94.7% of the positive scans and in 97.7% of the negatives. Two false positives and one false negative occurred. Very poor results were obtained in the same patients using conventional technetium and gallium scans: only 20.7% of these interpretations were correct. The method proved very helpful in differentiating malignant from benign lesions."} {"id": "PMID:177742", "title": "Simple radiometric techniques for rapid detection of herpes simplex virus type 1 in WI-38 cell culture.", "content": "Two radiometric techniques were developed for detecting the presence of herpes simplex virus type 1 in stationary monolayers of the diploid cell line WI-38. The time of detection was compared to that obtained from visual examination for cytopathic effects in the same cell line. Oxidation of 14C-1-glucose in infected and uninfected cells was determined by 14CO2 production, measured by an ionization chamber, and DNA synthesis was determined by 3H-thymidine incorporation, measured by scintillation counting. Compared to uninfected cells, infected cells showed a 23-26% reduction in 14C-1-glucose oxidation and a 355-498% increase in DNA synthesis 4-6 hr after infection. These changes in cellular metabolism were observed 14 hr before visible signs of cytopathic effects. The increase in DNA synthesis was completely inhibited by viral neutralization with herpes simplex antiserum. Increased DNA synthesis was observed 5 hr after infection with 10,000-3,200,000 TCID50 units of virus. These radiometric methods for the detection of viral effect on cellular metabolism are simple, fast, and objective.", "contents": "Simple radiometric techniques for rapid detection of herpes simplex virus type 1 in WI-38 cell culture. Two radiometric techniques were developed for detecting the presence of herpes simplex virus type 1 in stationary monolayers of the diploid cell line WI-38. The time of detection was compared to that obtained from visual examination for cytopathic effects in the same cell line. Oxidation of 14C-1-glucose in infected and uninfected cells was determined by 14CO2 production, measured by an ionization chamber, and DNA synthesis was determined by 3H-thymidine incorporation, measured by scintillation counting. Compared to uninfected cells, infected cells showed a 23-26% reduction in 14C-1-glucose oxidation and a 355-498% increase in DNA synthesis 4-6 hr after infection. These changes in cellular metabolism were observed 14 hr before visible signs of cytopathic effects. The increase in DNA synthesis was completely inhibited by viral neutralization with herpes simplex antiserum. Increased DNA synthesis was observed 5 hr after infection with 10,000-3,200,000 TCID50 units of virus. These radiometric methods for the detection of viral effect on cellular metabolism are simple, fast, and objective."} {"id": "PMID:177743", "title": "Cyclic AMP content of gingival fluid in women taking oral contraceptives.", "content": "Gingival fluid samples were collected from 12 healthy adult women who ranged in age from 19 to 34 years. Seven subjects with normal menstrual cycles who received no medications acted as controls while five subjects who had been using oral contraceptives for a minimum of 17 months constituted the experimental group. The women using birth control pills showed a 53% increase in the gingival fluid volume versus the controls. Radioimmunoassay revealed a mean concentration of cyclic adenosine monophosphate (cAMP) in the gingival fluid of 3.8-10(-6)M in the controls and 1.9-10(-6)M in subjects using oral contraceptives, although the total amount of cAMP present in the fluid from both groups was equal. These gingival fluid cAMP levels were a hundredfold higher than those measured in serum and saliva.", "contents": "Cyclic AMP content of gingival fluid in women taking oral contraceptives. Gingival fluid samples were collected from 12 healthy adult women who ranged in age from 19 to 34 years. Seven subjects with normal menstrual cycles who received no medications acted as controls while five subjects who had been using oral contraceptives for a minimum of 17 months constituted the experimental group. The women using birth control pills showed a 53% increase in the gingival fluid volume versus the controls. Radioimmunoassay revealed a mean concentration of cyclic adenosine monophosphate (cAMP) in the gingival fluid of 3.8-10(-6)M in the controls and 1.9-10(-6)M in subjects using oral contraceptives, although the total amount of cAMP present in the fluid from both groups was equal. These gingival fluid cAMP levels were a hundredfold higher than those measured in serum and saliva."} {"id": "PMID:177746", "title": "Formation of sulfhydryl groups in the walls of Eimeria stiedai and E. tenella oocysts subjected to in vitro excystation.", "content": "Eimeria stiedai or Eimeria tenella oocysts were incubated in aqueous cysteine hydrochloride (cysHCl) under carbon dioxide (CO2), aqueous cysHCl under air, water under CO2 or water under air, and analyzed for sulfhydryl (-SH) groups. The cysHCl-CO2 treatment produced more -SH groups than the other treatments and was effective in allowing activation of intact and sodium hypochlorite (NaOCl)-treated E. stiedai oocysts as well as NaOCl-treated E. tenella oocysts. The CO2-cysHCl complex may act directly on the oocyst wall, especially in the micropylar region, to unmask lipid-shielded disulfide bridges, which are reduced to -SH groups. The reduction apparently disturbs the protein superstructure of the oocyst wall, promotes opening of the micropyle, and changes the impermeable state of the sporulated oocyst.", "contents": "Formation of sulfhydryl groups in the walls of Eimeria stiedai and E. tenella oocysts subjected to in vitro excystation. Eimeria stiedai or Eimeria tenella oocysts were incubated in aqueous cysteine hydrochloride (cysHCl) under carbon dioxide (CO2), aqueous cysHCl under air, water under CO2 or water under air, and analyzed for sulfhydryl (-SH) groups. The cysHCl-CO2 treatment produced more -SH groups than the other treatments and was effective in allowing activation of intact and sodium hypochlorite (NaOCl)-treated E. stiedai oocysts as well as NaOCl-treated E. tenella oocysts. The CO2-cysHCl complex may act directly on the oocyst wall, especially in the micropylar region, to unmask lipid-shielded disulfide bridges, which are reduced to -SH groups. The reduction apparently disturbs the protein superstructure of the oocyst wall, promotes opening of the micropyle, and changes the impermeable state of the sporulated oocyst."} {"id": "PMID:177749", "title": "5'-nucleotide phosphodiesterase activity of floxuridine-resistant mouse glioma.", "content": "In tissue culture experiments, cells derived from glioma 26, a transplantable tumor of C57B1/6 mice, were sensitive to both floxuridine (5-fluorodeoxyuridine) and 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl)phosphate, an enzyme-mediated drug activated by 5'-nucleotide phosphodiesterase. When these compounds were tested on the tumor in animals at a level of 5 mg/kg for 5 days, tumor growth was inhibited approximately 20% by both compounds. When higher levels of 5-fluorodeoxyuridine, 100 mg/kg four times weekly throughout the lifespan of the mouse, were given, the tumor, although inhibited at first, developed resistance and continued to grow until it killed the animal. Phosphodiesterase levels in the tumor rose as the tumor grew. On the other hand, thymidine kinase levels dropped as anticipated from the known 5-fluorodeoxyuridine-resistant hepatoma tissue culture data. This enzyme pattern was maintained in transplantable mouse glioma lines established from the resistant tumors. One of these lines, tested at a level of 5 mg/kg for 5 days, showed no response to 5-fluorodeoxyuridine but was still sensitive to 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl) phosphate. These experiments, therefore, offer a model system and a rationale for the design and study of more compounds that could be activated by the enzyme phosphodiesterase. Such compounds might be used alternatively when resistance to 5-fluorodeoxyuridine develops, a common clinical experience in the use of this anticancer drug.", "contents": "5'-nucleotide phosphodiesterase activity of floxuridine-resistant mouse glioma. In tissue culture experiments, cells derived from glioma 26, a transplantable tumor of C57B1/6 mice, were sensitive to both floxuridine (5-fluorodeoxyuridine) and 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl)phosphate, an enzyme-mediated drug activated by 5'-nucleotide phosphodiesterase. When these compounds were tested on the tumor in animals at a level of 5 mg/kg for 5 days, tumor growth was inhibited approximately 20% by both compounds. When higher levels of 5-fluorodeoxyuridine, 100 mg/kg four times weekly throughout the lifespan of the mouse, were given, the tumor, although inhibited at first, developed resistance and continued to grow until it killed the animal. Phosphodiesterase levels in the tumor rose as the tumor grew. On the other hand, thymidine kinase levels dropped as anticipated from the known 5-fluorodeoxyuridine-resistant hepatoma tissue culture data. This enzyme pattern was maintained in transplantable mouse glioma lines established from the resistant tumors. One of these lines, tested at a level of 5 mg/kg for 5 days, showed no response to 5-fluorodeoxyuridine but was still sensitive to 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl) phosphate. These experiments, therefore, offer a model system and a rationale for the design and study of more compounds that could be activated by the enzyme phosphodiesterase. Such compounds might be used alternatively when resistance to 5-fluorodeoxyuridine develops, a common clinical experience in the use of this anticancer drug."} {"id": "PMID:177750", "title": "Anticonvulsant activity and selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations by 10-(2-arylimino-3-acetylamino-4-thiazolidonyl) phenothiazines.", "content": "Several Several 10-(1-acetyl-4-arylthiosemicarbazido) phenothiazines and their corresponding cyclized 10-(2-arylimino-3-acetylamino-4-thiazolidonyl)phenothiazines were synthetized and characterized by their sharp melting points and elemental analyses. All compounds inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate and alpha-ketoglutarate selectively, whereas NAD-independent oxidation of succinate remained unaltered. All phenothiazine derivatives exhibited anticonvulsant activity, which was reflected by the 20-60% protection observed against pentylenetetrazol-induced convulsions in mice. The ability of substituted thiosemicarbazidophenothiazines to inhibit cellular respiratory activity was reduced considerably by cyclization to the corresponding substituted thiazolidinophenothiazines. On the other hand, cyclization generally resulted in increased anticonvulsant activity. Thus, the anticonvulsant activity possessed by these substituted phenothiazines bore no relationship with their ability to inhibit selectively the NAD-dependent oxidations. Selective inhibition of NAD-dependent oxidation of pyruvate and alpha-ketoglutarate in isolated rat brain mitochondria by some 10-(1-acetyl-4-arylthiosemicarbazido) phenothiazines was concentration dependent and competitive in nature.", "contents": "Anticonvulsant activity and selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations by 10-(2-arylimino-3-acetylamino-4-thiazolidonyl) phenothiazines. Several Several 10-(1-acetyl-4-arylthiosemicarbazido) phenothiazines and their corresponding cyclized 10-(2-arylimino-3-acetylamino-4-thiazolidonyl)phenothiazines were synthetized and characterized by their sharp melting points and elemental analyses. All compounds inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate and alpha-ketoglutarate selectively, whereas NAD-independent oxidation of succinate remained unaltered. All phenothiazine derivatives exhibited anticonvulsant activity, which was reflected by the 20-60% protection observed against pentylenetetrazol-induced convulsions in mice. The ability of substituted thiosemicarbazidophenothiazines to inhibit cellular respiratory activity was reduced considerably by cyclization to the corresponding substituted thiazolidinophenothiazines. On the other hand, cyclization generally resulted in increased anticonvulsant activity. Thus, the anticonvulsant activity possessed by these substituted phenothiazines bore no relationship with their ability to inhibit selectively the NAD-dependent oxidations. Selective inhibition of NAD-dependent oxidation of pyruvate and alpha-ketoglutarate in isolated rat brain mitochondria by some 10-(1-acetyl-4-arylthiosemicarbazido) phenothiazines was concentration dependent and competitive in nature."} {"id": "PMID:177751", "title": "Fragmentation of 3-oximino-4-chromanone.", "content": "Heating either the methanesulfonate ester of 3-oximino-4-chromanone or 3-oximino-4-chromanone and an alternative acylating agent such as p-toluensulfonyl chloride or acetic anhydride in the presence of aqueous base afforded two major fragments: salicyclic acid and 2-carboxyphenoxyacetonitrile. These compounds are derived from two separate cleavage pathways involving the acylated oxime. In one pathway, fragmentation appears to be assisted by the ether ring oxygen; in the other, it is assisted by the alpha-carbonyl group of the oxime ester.", "contents": "Fragmentation of 3-oximino-4-chromanone. Heating either the methanesulfonate ester of 3-oximino-4-chromanone or 3-oximino-4-chromanone and an alternative acylating agent such as p-toluensulfonyl chloride or acetic anhydride in the presence of aqueous base afforded two major fragments: salicyclic acid and 2-carboxyphenoxyacetonitrile. These compounds are derived from two separate cleavage pathways involving the acylated oxime. In one pathway, fragmentation appears to be assisted by the ether ring oxygen; in the other, it is assisted by the alpha-carbonyl group of the oxime ester."} {"id": "PMID:177752", "title": "CNS depressant activity of pyrimidylthiazolidones and their selective inhibition of NAD-dependent pyruvate oxidation.", "content": "Several 1-aryl-3-(2-pyrimidyl)thiocarbamides and their corresponding cyclized 2-arylimino-3-(2-pyrimidyl)thiazolid-4-ones were synthesized and characterized by their sharp melting points and elemental analyses. These thiocarbamides and thiazolidones possessed anticonvulsant activity against pentylenetetrazol-induced convulsions and potentiated pentobarbital-induced hypnosis in mice. Most of these thiocarbamides and thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, where the use of added NAD dether hand, remained unaltered. The anticonvulsant activity of thiocarbamides and thiazolidones was unrelated to their ability to inhibit the respiratory activity of rat brain homogenates during oxidation of sodium pyruvate. Cyclization of thiocarbamides to the corresponding thiazolidones in general enhanced their CNS depressant and enzyme inhibitory effectiveness.", "contents": "CNS depressant activity of pyrimidylthiazolidones and their selective inhibition of NAD-dependent pyruvate oxidation. Several 1-aryl-3-(2-pyrimidyl)thiocarbamides and their corresponding cyclized 2-arylimino-3-(2-pyrimidyl)thiazolid-4-ones were synthesized and characterized by their sharp melting points and elemental analyses. These thiocarbamides and thiazolidones possessed anticonvulsant activity against pentylenetetrazol-induced convulsions and potentiated pentobarbital-induced hypnosis in mice. Most of these thiocarbamides and thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, where the use of added NAD dether hand, remained unaltered. The anticonvulsant activity of thiocarbamides and thiazolidones was unrelated to their ability to inhibit the respiratory activity of rat brain homogenates during oxidation of sodium pyruvate. Cyclization of thiocarbamides to the corresponding thiazolidones in general enhanced their CNS depressant and enzyme inhibitory effectiveness."} {"id": "PMID:177753", "title": "Investigations into the mechanism of reduction of ethanol sleep by thyrotropin-releasing hormone (TRH).", "content": "Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content. This reduction of the actions of ethanol was also apparent after oral or intracisternal administration of TRH. In addition, TRH reduced ethanol-induced sleep in rats, hamsters, gerbils and guinea pigs. Evidence that the pituitary-thyroid axis is not necessary for the effects of TRH was provided by observations that hypophysectomy did not reduce TRH antagonism of ethanol narcosis and findings that neither triiodothyronine nor thyrotropin mimicked its action. Certain analogs of TRH, which have little effect on the pituitary, were also found to antagonize ethanol-induced sleep and hypothermia. Pretreatment with the antiadrenergic drugs, alpha-methyltyrosine, phentolamine and propranolol did not antagonize the ability of TRH to reduce sleep induced by ethanol. However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent. In contrast, central administration of other anticholinergic drugs, such as delta-tobocurarine and hexamethonium, reduced ethanol-induced sleep and this effect was additive with TRH. Carbachol also reduced ethanol sleeping time and this effect was also blocked by atropine methyl nitrate. The antagonism of ethanol-induced sleep by dibutyryl cyclic adenosine 3', 5'-monophosphate was significantly reduced but not blocked by atropine methyl nitrate. Results provide evidence that TRH has a direct extrapituitary action on brain and that both TRH and ethanol may interact with central cholinergic systems.", "contents": "Investigations into the mechanism of reduction of ethanol sleep by thyrotropin-releasing hormone (TRH). Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content. This reduction of the actions of ethanol was also apparent after oral or intracisternal administration of TRH. In addition, TRH reduced ethanol-induced sleep in rats, hamsters, gerbils and guinea pigs. Evidence that the pituitary-thyroid axis is not necessary for the effects of TRH was provided by observations that hypophysectomy did not reduce TRH antagonism of ethanol narcosis and findings that neither triiodothyronine nor thyrotropin mimicked its action. Certain analogs of TRH, which have little effect on the pituitary, were also found to antagonize ethanol-induced sleep and hypothermia. Pretreatment with the antiadrenergic drugs, alpha-methyltyrosine, phentolamine and propranolol did not antagonize the ability of TRH to reduce sleep induced by ethanol. However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent. In contrast, central administration of other anticholinergic drugs, such as delta-tobocurarine and hexamethonium, reduced ethanol-induced sleep and this effect was additive with TRH. Carbachol also reduced ethanol sleeping time and this effect was also blocked by atropine methyl nitrate. The antagonism of ethanol-induced sleep by dibutyryl cyclic adenosine 3', 5'-monophosphate was significantly reduced but not blocked by atropine methyl nitrate. Results provide evidence that TRH has a direct extrapituitary action on brain and that both TRH and ethanol may interact with central cholinergic systems."} {"id": "PMID:177754", "title": "Onset of chronotropic effects of nicotinic drugs and tyramine on the sinoatrial pacemaker in chick embryo heart: relationship to the development of autonomic neuroeffector transmission.", "content": "Spontaneous electrical activity, recorded extracellularly from the sinoatriial pacemaker region in the isolated chick embryo heart, was inhibited by nicotine (10(-5)M) on the 11th incubation day and thereafter. Blockade of the inhibitory effects of nicotine hexamethonium, tetroditoxin and atropine supported the conclusion that nicotine initiated propagated impulses in postganglionic cholinergic nerves and released acetylcholine to act on atropine-sensitive receptors on pacemaker cells. Dimethylphenylpiperazinium, like nicotine, inhibited the sinoatrial pacemaker. The onset of the inhibitory effect of nicotine occurred within 1 day of the appearance of cholinergic neuroeffector transmission. The acceleratory action of tyramine (2.9 X 10(-5)M) increased markedly on the 20th incubation day, that is, within 1 day of the appearance of adrenergic neuroeffector transmission. The positive chronotropic effects of tyramine were opposed by cocaine and by propranolol. Nicotine also evoked pacemaker acceleration that was observed on the 21st incubation day and thereafter. However, the sympathomimetic effect of nicotine required elevation (2 times normal) of the external Ca++ concentration. Ontogenetic and pharmacologic evidence support the conclusion that the drug-induced changes in pacemaker impulse frequency depended upon an interaction with autonomic nerves. The results are consistent with the hypothesis that the gap between morphologic innervation of the heart by autonomic nerves and the appearance of transmission is related, at least in part, to the amount of transmitter available for release.", "contents": "Onset of chronotropic effects of nicotinic drugs and tyramine on the sinoatrial pacemaker in chick embryo heart: relationship to the development of autonomic neuroeffector transmission. Spontaneous electrical activity, recorded extracellularly from the sinoatriial pacemaker region in the isolated chick embryo heart, was inhibited by nicotine (10(-5)M) on the 11th incubation day and thereafter. Blockade of the inhibitory effects of nicotine hexamethonium, tetroditoxin and atropine supported the conclusion that nicotine initiated propagated impulses in postganglionic cholinergic nerves and released acetylcholine to act on atropine-sensitive receptors on pacemaker cells. Dimethylphenylpiperazinium, like nicotine, inhibited the sinoatrial pacemaker. The onset of the inhibitory effect of nicotine occurred within 1 day of the appearance of cholinergic neuroeffector transmission. The acceleratory action of tyramine (2.9 X 10(-5)M) increased markedly on the 20th incubation day, that is, within 1 day of the appearance of adrenergic neuroeffector transmission. The positive chronotropic effects of tyramine were opposed by cocaine and by propranolol. Nicotine also evoked pacemaker acceleration that was observed on the 21st incubation day and thereafter. However, the sympathomimetic effect of nicotine required elevation (2 times normal) of the external Ca++ concentration. Ontogenetic and pharmacologic evidence support the conclusion that the drug-induced changes in pacemaker impulse frequency depended upon an interaction with autonomic nerves. The results are consistent with the hypothesis that the gap between morphologic innervation of the heart by autonomic nerves and the appearance of transmission is related, at least in part, to the amount of transmitter available for release."} {"id": "PMID:177755", "title": "Effects of amide-linked local anesthetics on adrenergic neuroeffector junction in cutaneous veins of dog.", "content": "When changes in isometric tension of helical strips of dog saphenous veins were recorded, etidocaine caused a dose-dependent depression of the contractile responses to nerve stimulation, norepinephrine and K+. The response to nerve stimulation was significantly more depressed than that to exogenous norepinephrine. Similar results were obtained with lidocaine. In preparations incubated in solutions containing 3H-norepinephrine and mounted for superfusion and isometric tension recording, etidocaine depressed the contractions and diminished the release of 3H-norepinephrine evoked by nerve stimulation. Thus, in addition to an inhibitory effect on the responses of smooth muscle cells, amide-linked local anesthetic agents such as etidocaine depress adrenergic neurotransmission in the blood vessel wall, which helps explain their vasodilator properties in the intact organism. In unstimulated preparations and during contractions caused by K+, etidocaine increased the efflux of 3H-norepinephrine and deaminated metabolites. After incubation with the monamine oxidase inhibitor, pargyline, etidocaine augmented markedly the efflux of 3H-norepinephrine. During responses to tyramine, it augmented the release of 3H-norepinephrine more than the efflux of deaminated compounds. This suggests that etidocaine augments the leakage of norepinephrine out of the storage vesicles, making more catecholamines available for intraneuronal deamination.", "contents": "Effects of amide-linked local anesthetics on adrenergic neuroeffector junction in cutaneous veins of dog. When changes in isometric tension of helical strips of dog saphenous veins were recorded, etidocaine caused a dose-dependent depression of the contractile responses to nerve stimulation, norepinephrine and K+. The response to nerve stimulation was significantly more depressed than that to exogenous norepinephrine. Similar results were obtained with lidocaine. In preparations incubated in solutions containing 3H-norepinephrine and mounted for superfusion and isometric tension recording, etidocaine depressed the contractions and diminished the release of 3H-norepinephrine evoked by nerve stimulation. Thus, in addition to an inhibitory effect on the responses of smooth muscle cells, amide-linked local anesthetic agents such as etidocaine depress adrenergic neurotransmission in the blood vessel wall, which helps explain their vasodilator properties in the intact organism. In unstimulated preparations and during contractions caused by K+, etidocaine increased the efflux of 3H-norepinephrine and deaminated metabolites. After incubation with the monamine oxidase inhibitor, pargyline, etidocaine augmented markedly the efflux of 3H-norepinephrine. During responses to tyramine, it augmented the release of 3H-norepinephrine more than the efflux of deaminated compounds. This suggests that etidocaine augments the leakage of norepinephrine out of the storage vesicles, making more catecholamines available for intraneuronal deamination."} {"id": "PMID:177756", "title": "Selective lithium inhibition of hormonal phosphaturic responses.", "content": "The acute effects of intraperitoneal lithium on the phosphaturic responses to parathyroid hormone (PTH) and pharmacologic doses of vasopressin were studied in rats. Lithium significantly inhibited the phosphaturic response to PTH at a dosage of 90 mug/kg/hr but did not affect the response to 30 mug/kg/hr. Conversely, lithium eliminated the phosphaturic response to vasopressin at a dosage of 300 mU/kg/hr but did not affect the response to dibutyryl adenosine 3', 5'-monophosphate (db-cAMP), 10 mg/kg/hr. Renal lithium content was increased substantially after the larger dose of PTH and was diminished slightly after db-cAMP and the larger dose of vasopressin. The latter two treatments also inhibited renal lithium reabsorption whereas the smaller dose of vasopressin and both dosages of PTH did not. These results indicate that lithium interferes with the phosphaturic responses to certain dosages of pth and vasopressin and suggest that renal lithium reabsorption and tissue lithium uptake may in part determine the extent of this cation-hormonal interaction. In addition, a competitive type of interaction between lithium and vasopressin is postulated.", "contents": "Selective lithium inhibition of hormonal phosphaturic responses. The acute effects of intraperitoneal lithium on the phosphaturic responses to parathyroid hormone (PTH) and pharmacologic doses of vasopressin were studied in rats. Lithium significantly inhibited the phosphaturic response to PTH at a dosage of 90 mug/kg/hr but did not affect the response to 30 mug/kg/hr. Conversely, lithium eliminated the phosphaturic response to vasopressin at a dosage of 300 mU/kg/hr but did not affect the response to dibutyryl adenosine 3', 5'-monophosphate (db-cAMP), 10 mg/kg/hr. Renal lithium content was increased substantially after the larger dose of PTH and was diminished slightly after db-cAMP and the larger dose of vasopressin. The latter two treatments also inhibited renal lithium reabsorption whereas the smaller dose of vasopressin and both dosages of PTH did not. These results indicate that lithium interferes with the phosphaturic responses to certain dosages of pth and vasopressin and suggest that renal lithium reabsorption and tissue lithium uptake may in part determine the extent of this cation-hormonal interaction. In addition, a competitive type of interaction between lithium and vasopressin is postulated."} {"id": "PMID:177757", "title": "Positive inotropic activity of cholera enterotoxin on the embryonic chick heart.", "content": "The characteristics of the positive inotropic effect of different preparations of cholera toxin on the isolated 4-day-old embryonic chick heart were investigated. Crude (CCT) as well as partially purified and purified (PCT)preparations of cholera toxin were shown to have positive inotropic activity. Contractility was increased within 1 minute and reached a maximum at approximately 40 minutes after exposure to toxin. Activities of all three toxin preparations were abolished by heating, their effects were prevented by addition of antitoxin, but nort propranolol, before exposure of the heart to toxin. The positive inotropic effect of PCT was not reversed by washing, but was reversed by subsequent addition of antitoxin. The effects of CCT were reversed by insulin. Effects of both CCT and PCT were potentiated by theophylline, and both toxin preparations elevated tissue levels of cyclic adenosine 3',5'-monophosphate. A filtrate of CCT (MW is less than 30,000) exhibited similar cardiostimulant activity but displayed certain differences from the other toxin preparations. The filtrate was heat stable, and its effects were blocked by pretreatment with propranolol but not by antitoxin. The filtrate of CCT, unlike the toxin-containing preparations, did not stimulate intestinal fluid secretion in the dog.", "contents": "Positive inotropic activity of cholera enterotoxin on the embryonic chick heart. The characteristics of the positive inotropic effect of different preparations of cholera toxin on the isolated 4-day-old embryonic chick heart were investigated. Crude (CCT) as well as partially purified and purified (PCT)preparations of cholera toxin were shown to have positive inotropic activity. Contractility was increased within 1 minute and reached a maximum at approximately 40 minutes after exposure to toxin. Activities of all three toxin preparations were abolished by heating, their effects were prevented by addition of antitoxin, but nort propranolol, before exposure of the heart to toxin. The positive inotropic effect of PCT was not reversed by washing, but was reversed by subsequent addition of antitoxin. The effects of CCT were reversed by insulin. Effects of both CCT and PCT were potentiated by theophylline, and both toxin preparations elevated tissue levels of cyclic adenosine 3',5'-monophosphate. A filtrate of CCT (MW is less than 30,000) exhibited similar cardiostimulant activity but displayed certain differences from the other toxin preparations. The filtrate was heat stable, and its effects were blocked by pretreatment with propranolol but not by antitoxin. The filtrate of CCT, unlike the toxin-containing preparations, did not stimulate intestinal fluid secretion in the dog."} {"id": "PMID:177758", "title": "Dopamine synthesis in rat brain striatal synaptosomes. II. Dibutyryl cyclic adenosine 3':5'-monophosphoric acid and 6-methyltetrahydropterine-induced synthesis increases without an increase in endogenous dopamine release.", "content": "The effects of N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphoric acid (dibutyryl cyclic AMP), DL-6-methyl-5, 6, 7, 8-tetrahydropterine (6-MPH4) and tyramine on dopamine synthesis and endogenous dopamine release in rat brain striatal synaptosomes have been examined. Dibutyryl cyclic AMP (1 mM) produced a 100% increase in dopamine synthesis but had no effect on endogenous dopamine release. Veratridine (75 muM) did not further stimulate dibutyryl cyclic AMP-treated tissue. 6-MPH4 (0.1 mM) also stimulated synthesis without stimulating dopamine release. The stimulation produced by 6-MPH4 was additive to the stimulations produced by either dibutyryl cyclic AMP or veratridine. Tyramine (10(-4) M) inhibited synthesis, while increasing dopamine release. These data suggest that 1) dopamine-releasing agents may have differential effects upon dopamine synthesis, depending on their mechanism of release, 2) dopamine synthesis can be stimulated independently of endogenous dopamine release and 3) the pteridine cofactor necessary for tyrosine hydroxylation is not normally present at saturating levels.", "contents": "Dopamine synthesis in rat brain striatal synaptosomes. II. Dibutyryl cyclic adenosine 3':5'-monophosphoric acid and 6-methyltetrahydropterine-induced synthesis increases without an increase in endogenous dopamine release. The effects of N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphoric acid (dibutyryl cyclic AMP), DL-6-methyl-5, 6, 7, 8-tetrahydropterine (6-MPH4) and tyramine on dopamine synthesis and endogenous dopamine release in rat brain striatal synaptosomes have been examined. Dibutyryl cyclic AMP (1 mM) produced a 100% increase in dopamine synthesis but had no effect on endogenous dopamine release. Veratridine (75 muM) did not further stimulate dibutyryl cyclic AMP-treated tissue. 6-MPH4 (0.1 mM) also stimulated synthesis without stimulating dopamine release. The stimulation produced by 6-MPH4 was additive to the stimulations produced by either dibutyryl cyclic AMP or veratridine. Tyramine (10(-4) M) inhibited synthesis, while increasing dopamine release. These data suggest that 1) dopamine-releasing agents may have differential effects upon dopamine synthesis, depending on their mechanism of release, 2) dopamine synthesis can be stimulated independently of endogenous dopamine release and 3) the pteridine cofactor necessary for tyrosine hydroxylation is not normally present at saturating levels."} {"id": "PMID:177759", "title": "The membrane potential of rat diaphragm muscle fibres and the effect of denervation.", "content": "1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump.", "contents": "The membrane potential of rat diaphragm muscle fibres and the effect of denervation. 1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump."} {"id": "PMID:177760", "title": "[Adrenocortical responses to ACTH (author's transl)].", "content": "To characterize by a mathematical model the dynamics of adrenocortical responses to ACTH, the concentration of plasma corticosterone was measured following a series of injections and perfusions of ACTH to dexamethasone-treated male rats. A similar slope was observed during the rise of plasma corticosterone following graded pulse inputs, and the steady-state corticosterone secretion rate was shown to increase proportionally to the perfusion rate of ACTH up to saturation corresponding to maximal secretion. The data will be used, concurrently with our model of the dynamics of plasma cortiscosterone, for the identification of a mathematical model of the adrenocortical response to ACTH.", "contents": "[Adrenocortical responses to ACTH (author's transl)]. To characterize by a mathematical model the dynamics of adrenocortical responses to ACTH, the concentration of plasma corticosterone was measured following a series of injections and perfusions of ACTH to dexamethasone-treated male rats. A similar slope was observed during the rise of plasma corticosterone following graded pulse inputs, and the steady-state corticosterone secretion rate was shown to increase proportionally to the perfusion rate of ACTH up to saturation corresponding to maximal secretion. The data will be used, concurrently with our model of the dynamics of plasma cortiscosterone, for the identification of a mathematical model of the adrenocortical response to ACTH."} {"id": "PMID:177762", "title": "The attitudes of nursing students and others about mental illness.", "content": "Student nurses tend to report somewhat moderate attitudes toward mental illness in that they appear to be less radical than psychology students, but less conservative than teacher-students in education. The student nurses' attitudes are similar to those of psychiatric residents, but more radical than psychiatric nurses.", "contents": "The attitudes of nursing students and others about mental illness. Student nurses tend to report somewhat moderate attitudes toward mental illness in that they appear to be less radical than psychology students, but less conservative than teacher-students in education. The student nurses' attitudes are similar to those of psychiatric residents, but more radical than psychiatric nurses."} {"id": "PMID:177764", "title": "What are mental health nurses doing?", "content": "In the analysis of a select set of questions from a questionnaire designed to survey the major roles of the MHN in a large metropolitan DHR, a number of trends were suggested: 1. A majority of the nurses surveyed functioned highest in the nurse-clinician area, with the majority being able to participate in planning and evaluating of their roles. 2. The role of nurse-therapist appears to still be the least practiced function. 3. It appears that, overall, the outpatient nurse is able to function more independently than is the inpatient nurse. The impression from this sample of MHNs is that they are being asked to participate in areas which have been traditionally considered the territory of other disciplines, such as: therapy, policy-making, and family contacts. Hopefully, nursing will continue to expand its role as a team member of the multidisciplinary community mental health center.", "contents": "What are mental health nurses doing? In the analysis of a select set of questions from a questionnaire designed to survey the major roles of the MHN in a large metropolitan DHR, a number of trends were suggested: 1. A majority of the nurses surveyed functioned highest in the nurse-clinician area, with the majority being able to participate in planning and evaluating of their roles. 2. The role of nurse-therapist appears to still be the least practiced function. 3. It appears that, overall, the outpatient nurse is able to function more independently than is the inpatient nurse. The impression from this sample of MHNs is that they are being asked to participate in areas which have been traditionally considered the territory of other disciplines, such as: therapy, policy-making, and family contacts. Hopefully, nursing will continue to expand its role as a team member of the multidisciplinary community mental health center."} {"id": "PMID:177769", "title": "It's the staff that keeps the patients talking.", "content": "This article is a critical look at the ingredients necessary to encourage chronic psychiatric patients to speak in a group setting. This study suggests that those chronically hospitalized patients with little speech can be encouraged to increase their verbalizations. Staff presence was the critical factor in the increase of patient speech. The opportunity to gain unusual privileges did not substantially increase the patient speech. In essence, this study indicates that as the amount of conversation from the nursing staff increases, a corresponding increase in patient verbalization occurs.", "contents": "It's the staff that keeps the patients talking. This article is a critical look at the ingredients necessary to encourage chronic psychiatric patients to speak in a group setting. This study suggests that those chronically hospitalized patients with little speech can be encouraged to increase their verbalizations. Staff presence was the critical factor in the increase of patient speech. The opportunity to gain unusual privileges did not substantially increase the patient speech. In essence, this study indicates that as the amount of conversation from the nursing staff increases, a corresponding increase in patient verbalization occurs."} {"id": "PMID:177770", "title": "Group home program.", "content": "The success in this program was defined in terms of staying out of the hospital or in not regressing to a more intensive level of care requirement. By these criteria, we have been successful. Nine chronic patients have lived in the group home. Of these nine, two have become totally independent, five live in the group home, one went to a family care home, and one to a nursing home due to physical disease. Not one of the group is in a psychiatric institution, and only one had a setback. Presently, plans to expand this program with the assistance of a community group are being formulated.", "contents": "Group home program. The success in this program was defined in terms of staying out of the hospital or in not regressing to a more intensive level of care requirement. By these criteria, we have been successful. Nine chronic patients have lived in the group home. Of these nine, two have become totally independent, five live in the group home, one went to a family care home, and one to a nursing home due to physical disease. Not one of the group is in a psychiatric institution, and only one had a setback. Presently, plans to expand this program with the assistance of a community group are being formulated."} {"id": "PMID:177771", "title": "Organic organizational research in a psychiatric inpatient setting.", "content": "The author proposes that most traditional methods of collecting data about life in mental health settings tend to produce inaccurate information. He suggests a procedure of information-gathering that may be useful and illustrates the theory of organic research in application with a case study of a psychiatric inpatient setting attempting to develop a recreational program.", "contents": "Organic organizational research in a psychiatric inpatient setting. The author proposes that most traditional methods of collecting data about life in mental health settings tend to produce inaccurate information. He suggests a procedure of information-gathering that may be useful and illustrates the theory of organic research in application with a case study of a psychiatric inpatient setting attempting to develop a recreational program."} {"id": "PMID:177772", "title": "Psychophysiological reactions as a function of life stress and behavioral rigidity.", "content": "Studies have shown that vulnerability to disease is a function of psychosocial factors. This study hypothesized that disease onset is antedated by life changes and is influenced by the individual's \"behavioral rigidity.\" The subjects were 160 female college students from three undergraduate general elective courses. An index of life change (LCI) was administered to each subject, presenting descriptions of important pressures and conflicts, with instruction that she indicate which ones she had personally experienced during the past calender year. A test of behavioral rigidity was also administered. Responses to the LCI indicated that low life change subjects reported significantly fewer illnesses than did the high life change subjects. The results supported the hypothesis that life stress plays a significant role in the development of illnesses. Responses to the behavioral rigidity measure and subsequent analysis of the interaction between this variable and life change did not prove to be statistically significant. It should be noted, however, that high flexibility subjects did report fewer illnesses than low flexibility subjects within the low and high life change groups. Additional studies must be undertaken in order to assess the trend found for interaction effects.", "contents": "Psychophysiological reactions as a function of life stress and behavioral rigidity. Studies have shown that vulnerability to disease is a function of psychosocial factors. This study hypothesized that disease onset is antedated by life changes and is influenced by the individual's \"behavioral rigidity.\" The subjects were 160 female college students from three undergraduate general elective courses. An index of life change (LCI) was administered to each subject, presenting descriptions of important pressures and conflicts, with instruction that she indicate which ones she had personally experienced during the past calender year. A test of behavioral rigidity was also administered. Responses to the LCI indicated that low life change subjects reported significantly fewer illnesses than did the high life change subjects. The results supported the hypothesis that life stress plays a significant role in the development of illnesses. Responses to the behavioral rigidity measure and subsequent analysis of the interaction between this variable and life change did not prove to be statistically significant. It should be noted, however, that high flexibility subjects did report fewer illnesses than low flexibility subjects within the low and high life change groups. Additional studies must be undertaken in order to assess the trend found for interaction effects."} {"id": "PMID:177773", "title": "The application of psychotherapeutic conceptual models in nursing practice.", "content": "Nurses, in order for their practice to be at a scientific level, need to consciously apply laws of change and stability of human behavior that have been identified by the behavioral sciences--especially psychotherapeutic theories. These are separated into several conceptual models which are organized around assumptions of the etiology of human behavior based on scientific observation and experimentation. They differ in emphasis and manipulation of the psychic elements of magic, faith, adaptation, and intellect. The beginning practitioner will probably find applying concepts from one model at a time most effective. She should base her choice on the congruence of the assumptions and emphasis of the models and her nursing assessment of the problem and her own philosophy of nursing. Her resulting choices of nursing intervention using a psychotherapeutic model should yield predictable goal attainment.", "contents": "The application of psychotherapeutic conceptual models in nursing practice. Nurses, in order for their practice to be at a scientific level, need to consciously apply laws of change and stability of human behavior that have been identified by the behavioral sciences--especially psychotherapeutic theories. These are separated into several conceptual models which are organized around assumptions of the etiology of human behavior based on scientific observation and experimentation. They differ in emphasis and manipulation of the psychic elements of magic, faith, adaptation, and intellect. The beginning practitioner will probably find applying concepts from one model at a time most effective. She should base her choice on the congruence of the assumptions and emphasis of the models and her nursing assessment of the problem and her own philosophy of nursing. Her resulting choices of nursing intervention using a psychotherapeutic model should yield predictable goal attainment."} {"id": "PMID:177780", "title": "The \"herd approach\" to bovine reproductive disorders. Part I: The diagnosis and management of infectious infertility.", "content": "The authors describe the methods employed by the Artificial Insemination Section of the Division of Veterinary Services in collaboration with the Reproduction and Bacteriology Section of the Veterinary Research Institute, Onderstepoort when herds are examined for infertility. A \"herd\" rather than an \"individual animal\" approach is advocated and certain infectious causes of infertility are discussed.", "contents": "The \"herd approach\" to bovine reproductive disorders. Part I: The diagnosis and management of infectious infertility. The authors describe the methods employed by the Artificial Insemination Section of the Division of Veterinary Services in collaboration with the Reproduction and Bacteriology Section of the Veterinary Research Institute, Onderstepoort when herds are examined for infertility. A \"herd\" rather than an \"individual animal\" approach is advocated and certain infectious causes of infertility are discussed."} {"id": "PMID:177781", "title": "Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs.", "content": "The 5'-O-p-tolylsulfonyl derivatives of 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine were synthesized and converted into the corresponding 5-halo-5'-azido-2',5'-dideoxyuridines (5-7). Reduction of 5-chloro-5'-azido-2',5'-dideoxyuridine (5) afforded 5-chloro-5'-amino-2',5'-dideoxyuridine (10, ACIU); however, similar efforts to prepare 5-bromo-5'-amino-2',5'-dideoxyuridine (11) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12) by reduction of the corresponding 5'-azido precursor resulted in the formation of 5'-amino-2',5'-dideoxyuridine (9). 5-Bromo-5'-amino-2',5'-dideoxyuridine (11, ABrU) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12, AIU) were prepared by halogenation of the 5-mercuriacetate of 5'-amino-2',5'-dideoxyuridine. The 5'-amino-2',5'-dideoxy analogs of 5-methyl-, 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine possess antiviral activity against herpes simplex virus but exhibit no inhibitory activity against sarcoma 180 (murine) or Vero (monkey) cells in culture.", "contents": "Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs. The 5'-O-p-tolylsulfonyl derivatives of 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine were synthesized and converted into the corresponding 5-halo-5'-azido-2',5'-dideoxyuridines (5-7). Reduction of 5-chloro-5'-azido-2',5'-dideoxyuridine (5) afforded 5-chloro-5'-amino-2',5'-dideoxyuridine (10, ACIU); however, similar efforts to prepare 5-bromo-5'-amino-2',5'-dideoxyuridine (11) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12) by reduction of the corresponding 5'-azido precursor resulted in the formation of 5'-amino-2',5'-dideoxyuridine (9). 5-Bromo-5'-amino-2',5'-dideoxyuridine (11, ABrU) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12, AIU) were prepared by halogenation of the 5-mercuriacetate of 5'-amino-2',5'-dideoxyuridine. The 5'-amino-2',5'-dideoxy analogs of 5-methyl-, 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine possess antiviral activity against herpes simplex virus but exhibit no inhibitory activity against sarcoma 180 (murine) or Vero (monkey) cells in culture."} {"id": "PMID:177782", "title": "Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine.", "content": "A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries. A series of 1,3-dialkyluracils was of low potency as inhibitors of either peak I or peak II. The 7-substituted xanthines were prepared by alkylation of MIX with the corresponding alkyl or aralkyl halide in DMF containing K2CO3. These compounds were, in general, much less potent inhibitors of peak II activity than was MIX, but some of them retained the potency of MIX as inhibitors of peak I and, therefore, were relatively specific for inhibition of peak I. 7-Bzl-MIX was the most selective compound tested; it was a potent inhibitor of peak I activity but was much less effective as an inhibitor of peak II activity. Substitution of either electron-withdrawing (nitro) or electron-donating (methoxy) groups on the 7-benzyl moiety reduced the effectiveness of the 7-benzyl compounds as inhibitors of peak I. Chlorobenzyl substitution increased the potency slightly over the benzyl but not the selectivity between peaks.", "contents": "Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine. A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries. A series of 1,3-dialkyluracils was of low potency as inhibitors of either peak I or peak II. The 7-substituted xanthines were prepared by alkylation of MIX with the corresponding alkyl or aralkyl halide in DMF containing K2CO3. These compounds were, in general, much less potent inhibitors of peak II activity than was MIX, but some of them retained the potency of MIX as inhibitors of peak I and, therefore, were relatively specific for inhibition of peak I. 7-Bzl-MIX was the most selective compound tested; it was a potent inhibitor of peak I activity but was much less effective as an inhibitor of peak II activity. Substitution of either electron-withdrawing (nitro) or electron-donating (methoxy) groups on the 7-benzyl moiety reduced the effectiveness of the 7-benzyl compounds as inhibitors of peak I. Chlorobenzyl substitution increased the potency slightly over the benzyl but not the selectivity between peaks."} {"id": "PMID:177783", "title": "Regulation of ion permeabilities of isolated rat liver cells by external calcium concentration and temperature.", "content": "Regulation of ion transport through the plasma membrane was studied on single cell suspensions of hepatocytes, obtained after perfusion of rat liver with collagenase/hyaluronidase solution. Steady-state intracellular K and Na contents were shown to be markedly dependent on external Ca concentration and temperature, the sum of both ion concentrations remaining nearly constant. In contrast, steady-state intracellular chloride content was found to be independent of external Ca concentration, but dependent on temperature. Using the constant field relations, the passive permeabilities PK and PCl for potassium and chloride, respectively, were derived from the experimental data. At temperatures at and above 37 degrees C, with increasing external Ca concentration, PK, exhibits a sharp decrease at about 10(-4)M. In contrast, PCl at 37 degrees C was found to be independent of Ca concentration within experimental error. Earth alkali ions other than Ca, show marked but different effects on PK if compared at equal concentrations. Preincubation of the cells with cholesterol leads to a broadening of the dependence of PK on external Ca concentration. The above results, as well as those on the dependence of PK on external Ca concentration obtained by other authors, could be quantitatively described by a theoretical model of the plasma membrane proposed earlier. This model postulates regulatory binding sites, which cooperatively undergo a cation exchange of divalent cations by K+ ions from the external medium if the cation composition of the latter is altered.", "contents": "Regulation of ion permeabilities of isolated rat liver cells by external calcium concentration and temperature. Regulation of ion transport through the plasma membrane was studied on single cell suspensions of hepatocytes, obtained after perfusion of rat liver with collagenase/hyaluronidase solution. Steady-state intracellular K and Na contents were shown to be markedly dependent on external Ca concentration and temperature, the sum of both ion concentrations remaining nearly constant. In contrast, steady-state intracellular chloride content was found to be independent of external Ca concentration, but dependent on temperature. Using the constant field relations, the passive permeabilities PK and PCl for potassium and chloride, respectively, were derived from the experimental data. At temperatures at and above 37 degrees C, with increasing external Ca concentration, PK, exhibits a sharp decrease at about 10(-4)M. In contrast, PCl at 37 degrees C was found to be independent of Ca concentration within experimental error. Earth alkali ions other than Ca, show marked but different effects on PK if compared at equal concentrations. Preincubation of the cells with cholesterol leads to a broadening of the dependence of PK on external Ca concentration. The above results, as well as those on the dependence of PK on external Ca concentration obtained by other authors, could be quantitatively described by a theoretical model of the plasma membrane proposed earlier. This model postulates regulatory binding sites, which cooperatively undergo a cation exchange of divalent cations by K+ ions from the external medium if the cation composition of the latter is altered."} {"id": "PMID:177785", "title": "The assessment of nocturnal REM erection in the differential diagnosis of sexual impotence.", "content": "A new method for differentiating psychogenic from organic cases of sexual impotence is described based on the assesst of nocturnal REM erection in nine patients. It is our tentative impression that in psychogenic impotence nocturnal REM erection may be normal in amount and degree and an excellent indicator of erectile potential. In these cases a marked discrepancy exists between the amount and degree of nocturnal erection and the patient's daytime performance level attained during attempted coitus or masturbation. In the organic patients, on the contrary, such a discrepancy does not exist; instead, the maximal nocturnal erection attained corresponds closely to and mirrors the patient's impaired waking performance. This new method may be very useful in the diagnosis, prognosis, and decision as to type of treatment, especially in difficult cases.", "contents": "The assessment of nocturnal REM erection in the differential diagnosis of sexual impotence. A new method for differentiating psychogenic from organic cases of sexual impotence is described based on the assesst of nocturnal REM erection in nine patients. It is our tentative impression that in psychogenic impotence nocturnal REM erection may be normal in amount and degree and an excellent indicator of erectile potential. In these cases a marked discrepancy exists between the amount and degree of nocturnal erection and the patient's daytime performance level attained during attempted coitus or masturbation. In the organic patients, on the contrary, such a discrepancy does not exist; instead, the maximal nocturnal erection attained corresponds closely to and mirrors the patient's impaired waking performance. This new method may be very useful in the diagnosis, prognosis, and decision as to type of treatment, especially in difficult cases."} {"id": "PMID:177786", "title": "Mouse mammary tumor virus as a model for viral carcinogenesis.", "content": "Evidence is presented suggesting that genetic control may be the limiting factor in mammary tumor virus (MTV) positive mammary oncogenesis. Studies with hybrid mice involving high and low MTV-expressing murine strains suggest that expression of MTV in milk may not be as important in tumorigenesis as previously thought. The usefulness of the murine MTV model in the study of mammary malignancy is discussed.", "contents": "Mouse mammary tumor virus as a model for viral carcinogenesis. Evidence is presented suggesting that genetic control may be the limiting factor in mammary tumor virus (MTV) positive mammary oncogenesis. Studies with hybrid mice involving high and low MTV-expressing murine strains suggest that expression of MTV in milk may not be as important in tumorigenesis as previously thought. The usefulness of the murine MTV model in the study of mammary malignancy is discussed."} {"id": "PMID:177787", "title": "Mammary gland as a morphological end point in carcinogenesis studies.", "content": "The murine mammary tumor system is characterized by the presence of intermediate preneoplastic mammary cell populations. The intermediate mammary cell populations are characterized as either alveolar hyperplasias or ductal hyperplasias. The most frequently encountered preneoplastic cell population is the hyperplastic alveolar nodule, which has been extensively characterized with respect to its biological and hormonal properties. While the alveolar hyperplasias are seen predominantly in mice infected with the mammary tumor virus, ductal hyperplasias are seen primarily in mice treated with chemical carcinogens. Both types of lesions can serve as morphological end points for carcinogenesis studies in the mammary gland.", "contents": "Mammary gland as a morphological end point in carcinogenesis studies. The murine mammary tumor system is characterized by the presence of intermediate preneoplastic mammary cell populations. The intermediate mammary cell populations are characterized as either alveolar hyperplasias or ductal hyperplasias. The most frequently encountered preneoplastic cell population is the hyperplastic alveolar nodule, which has been extensively characterized with respect to its biological and hormonal properties. While the alveolar hyperplasias are seen predominantly in mice infected with the mammary tumor virus, ductal hyperplasias are seen primarily in mice treated with chemical carcinogens. Both types of lesions can serve as morphological end points for carcinogenesis studies in the mammary gland."} {"id": "PMID:177788", "title": "Estrogen-receptor binding: relationship to estrogen-induced responses.", "content": "The relationship between nuclear binding of the receptor-estrogen complex (R-E) and estrogenic responses was examined. Nuclear-bound R-E was measured by the [3H] estradiol exchange assay, which permits the quantification of R-E as a function of either endogenous or non labeled estrogen. The quantity of nuclear R-E fluctuated as a function of blood levels of estrogen during the estrous cycle in the rat. This indicates that the accumulation of the R-E complex by the nucleus of uterine cells may be of physiologic significance and under the control of endogenous estrogen.", "contents": "Estrogen-receptor binding: relationship to estrogen-induced responses. The relationship between nuclear binding of the receptor-estrogen complex (R-E) and estrogenic responses was examined. Nuclear-bound R-E was measured by the [3H] estradiol exchange assay, which permits the quantification of R-E as a function of either endogenous or non labeled estrogen. The quantity of nuclear R-E fluctuated as a function of blood levels of estrogen during the estrous cycle in the rat. This indicates that the accumulation of the R-E complex by the nucleus of uterine cells may be of physiologic significance and under the control of endogenous estrogen."} {"id": "PMID:177789", "title": "Vinblastine: influence on nerve conduction and synaptic transmission.", "content": "Vinblastine injected into the eyes of pigeons had a detrimental effect on the amplitude of the postsynaptic evoked potential in the optic tectum; impulse conduction of the optic nerve was not influenced. The depression of the postsynaptic evoked potential was dependent on the dosage. Only 20 and 100 mug vinblastine had an influence; no influence was observed with 10 mug vinblastine. The reversible depression was seen from the third day after injection to between the 21st and the 28th day after injection, and in that period it remained constant. The latency of the response was not influenced by vinblastine.", "contents": "Vinblastine: influence on nerve conduction and synaptic transmission. Vinblastine injected into the eyes of pigeons had a detrimental effect on the amplitude of the postsynaptic evoked potential in the optic tectum; impulse conduction of the optic nerve was not influenced. The depression of the postsynaptic evoked potential was dependent on the dosage. Only 20 and 100 mug vinblastine had an influence; no influence was observed with 10 mug vinblastine. The reversible depression was seen from the third day after injection to between the 21st and the 28th day after injection, and in that period it remained constant. The latency of the response was not influenced by vinblastine."} {"id": "PMID:177790", "title": "The effect of trimethadione on brain energy metabolism and EEG activity of the conscious rat exposed to HPO.", "content": "The use of trimethadione (TMO) as a protector in hyperbaric oxygen toxicity in the conscious rat has been examined in detail. The oxidation-reduction state of pyridine nucleotides was measured simultaneously with the EEG activity from the surface of the brain cortex. From the data obtained, a few parameters were calculated. The results show that in TMO-treated animals the time to the onset of convulsions, the time to the onset of NADH oxidation-reduction cycles, and the survival time were significantly longer than in the control group. The effect of TMO on the EEG shows that the tonic phase of the convulsive activity was almost completely abolished.", "contents": "The effect of trimethadione on brain energy metabolism and EEG activity of the conscious rat exposed to HPO. The use of trimethadione (TMO) as a protector in hyperbaric oxygen toxicity in the conscious rat has been examined in detail. The oxidation-reduction state of pyridine nucleotides was measured simultaneously with the EEG activity from the surface of the brain cortex. From the data obtained, a few parameters were calculated. The results show that in TMO-treated animals the time to the onset of convulsions, the time to the onset of NADH oxidation-reduction cycles, and the survival time were significantly longer than in the control group. The effect of TMO on the EEG shows that the tonic phase of the convulsive activity was almost completely abolished."} {"id": "PMID:177791", "title": "Ureteral metastasis from Wilms tumor.", "content": "Urothelial spread of Wilms tumor is uncommon and only 5 instances of ureteral metastases have been reported previously. A case of Wilms tumor with mid ureteral metastasis is presented and the literature is reviewed. Clinical implications and suggestions for surgical management are discussed.", "contents": "Ureteral metastasis from Wilms tumor. Urothelial spread of Wilms tumor is uncommon and only 5 instances of ureteral metastases have been reported previously. A case of Wilms tumor with mid ureteral metastasis is presented and the literature is reviewed. Clinical implications and suggestions for surgical management are discussed."} {"id": "PMID:177792", "title": "Coxsackievirus and adenovirus infection. Association with acute febrile and juvenile rheumatoid arthritis.", "content": "The prearthritic manifestations of juvenile rheumatoid arthritis in a 16-year-old boy were associated with a rise in coxsackievirus B3 and A9 neutralizing antibody titers from 1:16 to larger than or equal to 1:512, and 1:64 to 1:512, respectively. Recurrent polyarthritis followed and has persisted for three years. Adenovirus 7 was isolated from the pericardial fluid of a 9-year-old girl in whom juvenile rheumatoid arthritis then developed. Of 11 patients with acute, nonspecific, febrile arthritis subsequently studied, fourfold or greater antibody elevations occurred against coxsackieviruses in five, and against rubella and varicella-zoster virus in two. Antibody titers against other viral (and Mycoplasma) antigens remained stable. These findings suggest that coxsackieviruses, as well as other common viruses, may cause acute, nonspecific, febrile arthritis. In certain instances, such infection may be related to the development of juvenile rheumatoid arthritis.", "contents": "Coxsackievirus and adenovirus infection. Association with acute febrile and juvenile rheumatoid arthritis. The prearthritic manifestations of juvenile rheumatoid arthritis in a 16-year-old boy were associated with a rise in coxsackievirus B3 and A9 neutralizing antibody titers from 1:16 to larger than or equal to 1:512, and 1:64 to 1:512, respectively. Recurrent polyarthritis followed and has persisted for three years. Adenovirus 7 was isolated from the pericardial fluid of a 9-year-old girl in whom juvenile rheumatoid arthritis then developed. Of 11 patients with acute, nonspecific, febrile arthritis subsequently studied, fourfold or greater antibody elevations occurred against coxsackieviruses in five, and against rubella and varicella-zoster virus in two. Antibody titers against other viral (and Mycoplasma) antigens remained stable. These findings suggest that coxsackieviruses, as well as other common viruses, may cause acute, nonspecific, febrile arthritis. In certain instances, such infection may be related to the development of juvenile rheumatoid arthritis."} {"id": "PMID:177793", "title": "Effects of polyamines on the proliferation of mammalian cells in tissue culture.", "content": "Spermine, spermidine, putrescine and agmatine were examined for their cytotoxicity to mammalian cells in tissue culture. Spermine exhibited the highest cytotoxicity among them. It was followed by spermidine. Putrescine and agmatine showed little toxicity but rather acceleration of cell proliferation in some concentrations. Among 16 kinds of rat cells and strains and a mouse cell strain examined, liver cells, fibroblasts, and cells serially grown in a protein-free synthetic medium were sensitive to spermine in the order described. Normal liver cells were more sensitive than hepatoma cells, and normal fibroblasts were also more sensitive than sarcoma cells. Bovine serum albumin fraction markedly accelerated the cytotoxicity of spermine.", "contents": "Effects of polyamines on the proliferation of mammalian cells in tissue culture. Spermine, spermidine, putrescine and agmatine were examined for their cytotoxicity to mammalian cells in tissue culture. Spermine exhibited the highest cytotoxicity among them. It was followed by spermidine. Putrescine and agmatine showed little toxicity but rather acceleration of cell proliferation in some concentrations. Among 16 kinds of rat cells and strains and a mouse cell strain examined, liver cells, fibroblasts, and cells serially grown in a protein-free synthetic medium were sensitive to spermine in the order described. Normal liver cells were more sensitive than hepatoma cells, and normal fibroblasts were also more sensitive than sarcoma cells. Bovine serum albumin fraction markedly accelerated the cytotoxicity of spermine."} {"id": "PMID:177794", "title": "Isolation of low-virulent mouse hepatitis virus from nude mice with wasting syndrome and hepatitis.", "content": "Mouse hepatitis viruses were isolated on DBT cell culture from affected livers in most nude mice having wasting syndrome and chronic hepatitis. These nude isolates were pathogenic for cortisone-treated ICR weanling mice but not for non-treated ones.", "contents": "Isolation of low-virulent mouse hepatitis virus from nude mice with wasting syndrome and hepatitis. Mouse hepatitis viruses were isolated on DBT cell culture from affected livers in most nude mice having wasting syndrome and chronic hepatitis. These nude isolates were pathogenic for cortisone-treated ICR weanling mice but not for non-treated ones."} {"id": "PMID:177795", "title": "The effect of 2, 4-dinitrophenol on the growth of Bordetella pertussis in chick tracheal organ culture.", "content": "Among various metabolic inhibitors tested, only 2, 4-dinitrophenol inhibited the growth of Bordetella pertussis in chick tracheal organ culture at concentrations nontoxic both for bacterial organisms and for ciliary motility of the tracheal fragments. Although this effect of 2, 4-dinitrophenol was reversible in its early stage, longer treatment with this inhibitor resulted in an irreversible inhibition of bacterial growth due to secondary damage of the tracheal fragments. From these observations, it was postulated that the energy required for bacterial growth might be derived from cellular metabolism sensitive to inhibition with 2, 4-dinitrophenol.", "contents": "The effect of 2, 4-dinitrophenol on the growth of Bordetella pertussis in chick tracheal organ culture. Among various metabolic inhibitors tested, only 2, 4-dinitrophenol inhibited the growth of Bordetella pertussis in chick tracheal organ culture at concentrations nontoxic both for bacterial organisms and for ciliary motility of the tracheal fragments. Although this effect of 2, 4-dinitrophenol was reversible in its early stage, longer treatment with this inhibitor resulted in an irreversible inhibition of bacterial growth due to secondary damage of the tracheal fragments. From these observations, it was postulated that the energy required for bacterial growth might be derived from cellular metabolism sensitive to inhibition with 2, 4-dinitrophenol."} {"id": "PMID:177799", "title": "Relationship between the levels of intracellular cyclic nucleotides and mechanical responses induced by drugs.", "content": "The tracheal smooth muscle dissected free from connective tissues was used as a test preparation, since isoprenaline caused a decrease in cyclic GMP in the muscle while it caused an increase in cyclic GMP in the remaining tracheal tissue. Acetylcholine, histamine and papaverine increased both cyclic AMP and cyclic GMP levels in the tracheal muscle. Isoprenaline increased the cyclic AMP level but decreased the cyclic GMP level. However, when tracheal muscle was incubated with isoprenaline in the presence of acetylcholine, isoprenaline did not cause a decrease in cyclic GMP but rather a significant increase in cyclic AMP after only 1 min incubation. These results indicate that the relaxation of the tracheal muscle by isoprenaline is initiated by the increase in cyclic AMP but is not associated with the change in cyclic GMP.", "contents": "Relationship between the levels of intracellular cyclic nucleotides and mechanical responses induced by drugs. The tracheal smooth muscle dissected free from connective tissues was used as a test preparation, since isoprenaline caused a decrease in cyclic GMP in the muscle while it caused an increase in cyclic GMP in the remaining tracheal tissue. Acetylcholine, histamine and papaverine increased both cyclic AMP and cyclic GMP levels in the tracheal muscle. Isoprenaline increased the cyclic AMP level but decreased the cyclic GMP level. However, when tracheal muscle was incubated with isoprenaline in the presence of acetylcholine, isoprenaline did not cause a decrease in cyclic GMP but rather a significant increase in cyclic AMP after only 1 min incubation. These results indicate that the relaxation of the tracheal muscle by isoprenaline is initiated by the increase in cyclic AMP but is not associated with the change in cyclic GMP."} {"id": "PMID:177800", "title": "Mechanism of action of a new anti-inflammatory agent, naproxen (II). Effects of naproxen on activities of mucopolysaccharase, acid protease and collagenolytic enzymes in inflamed tissues.", "content": "In order to elucidate the biochemical anti-inflammatory properties of naproxen, the effects of this compound on activities of mucopolysaccharase [beta-glucuronidase (beta-Gase) and lysozyme (LZ)], acid protease (APase) and collagenolytic enzyme (CL) in inflamed tissues were investigated by means of a proliferative inflammatory model in filter-paper-implanted rats. In the preventive test, naproxen strongly inhibited granuloma formation and exudate accumulation as did indomethacin and prednisolone. Although the inhibitory effects of naproxen on all these enzymes were quite evident, indomethacin failed to inhibit APase activity. Prednisolone did not significantly inhibit LZ and APase activities in granuloma. In the curative test, prednisolone caused a marked decrease in the weight of the granuloma already formed and in the volume of the exudate, but with naproxen and indomethacin there was only a slight decrease. Naproxen and indomethacin induced slight but significant inhibition of LZ and CL activities, while prednisolone showing a weak inhibition of CL activity only. From these results, it may be concluded that anti-inflammatory and anti-rheumatic effects of naproxen are partly attributable to its inhibitory actions on these lysosomal enzymes.", "contents": "Mechanism of action of a new anti-inflammatory agent, naproxen (II). Effects of naproxen on activities of mucopolysaccharase, acid protease and collagenolytic enzymes in inflamed tissues. In order to elucidate the biochemical anti-inflammatory properties of naproxen, the effects of this compound on activities of mucopolysaccharase [beta-glucuronidase (beta-Gase) and lysozyme (LZ)], acid protease (APase) and collagenolytic enzyme (CL) in inflamed tissues were investigated by means of a proliferative inflammatory model in filter-paper-implanted rats. In the preventive test, naproxen strongly inhibited granuloma formation and exudate accumulation as did indomethacin and prednisolone. Although the inhibitory effects of naproxen on all these enzymes were quite evident, indomethacin failed to inhibit APase activity. Prednisolone did not significantly inhibit LZ and APase activities in granuloma. In the curative test, prednisolone caused a marked decrease in the weight of the granuloma already formed and in the volume of the exudate, but with naproxen and indomethacin there was only a slight decrease. Naproxen and indomethacin induced slight but significant inhibition of LZ and CL activities, while prednisolone showing a weak inhibition of CL activity only. From these results, it may be concluded that anti-inflammatory and anti-rheumatic effects of naproxen are partly attributable to its inhibitory actions on these lysosomal enzymes."} {"id": "PMID:177803", "title": "[Treatment of primary hyperlipoproteinemias type IV with different biguanides (author's transl)].", "content": "In 12 patients with primary type IV hyperlipoproteinemia the lipid lowering effect of constant doses of the biguanides metformin, phenformin and buformin was compared. After a 2 months dietary period bodyweight and initial triglyceride and cholesterol plasma concentrations were stabilized. The three biguanides were given for two months each, and this 6 months drug period was followed by another dietary period. While, 0.15 g phenformin and 2.55 g metformin reduced triglycerides by about 50% the reduction by 0.30 g buformin was only half. This was due to 4 nonresponders with initial triglycerides of more than 700 mg/100 ml. In contrast the triglyceride lowering effect of the other two biguanides was positively correlated to the pretreatment triglycerides. The cholesterol lowering effect of biguanide treatment was far less pronounced. There were no significant alterations of body weight and no influence on basal insulin and glucose concentrations. In conclusion, all three biguanides tested in a dosis of 3 tablets each are effective in lowering triglycerides although differing in efficiency and depending from the degree of typ IV hyperlipoproteinemia.", "contents": "[Treatment of primary hyperlipoproteinemias type IV with different biguanides (author's transl)]. In 12 patients with primary type IV hyperlipoproteinemia the lipid lowering effect of constant doses of the biguanides metformin, phenformin and buformin was compared. After a 2 months dietary period bodyweight and initial triglyceride and cholesterol plasma concentrations were stabilized. The three biguanides were given for two months each, and this 6 months drug period was followed by another dietary period. While, 0.15 g phenformin and 2.55 g metformin reduced triglycerides by about 50% the reduction by 0.30 g buformin was only half. This was due to 4 nonresponders with initial triglycerides of more than 700 mg/100 ml. In contrast the triglyceride lowering effect of the other two biguanides was positively correlated to the pretreatment triglycerides. The cholesterol lowering effect of biguanide treatment was far less pronounced. There were no significant alterations of body weight and no influence on basal insulin and glucose concentrations. In conclusion, all three biguanides tested in a dosis of 3 tablets each are effective in lowering triglycerides although differing in efficiency and depending from the degree of typ IV hyperlipoproteinemia."} {"id": "PMID:177804", "title": "[Stimulation of growth hormone and prolactin secretion with TRH in acromegaly (author's transl)].", "content": "Inappropriate stimulation of growth hormone (hGH)-secretion with TRH in acromegalic subjects has been shown previously, whereas prolactin (hPRL) secretion was reported to be blunted in active acromegaly. In this study TRH induced hGH and hPRL secretion was investigated in 23 active (mean hGH level: 68.5 +/- 19.9 ng/ml; +/- SE) and 15 inactive acromegalics (mean hGH level: 2.3 +/- 0.4 ng/ml; +/- SE). Fourteen of the active acromegalics showed a significant increase up to more than double of the basal hGH level after 200 mug TRH while in only one of the inactive acromegalics an inappropriate rise of hGH was induced by TRH. Basal hPRL levels were elevated in 9 and within normal range in 14 of the patients with active acromegaly. Except in 3 patients who had normal basal hPRL levels and in one patient with excessively elevated hPRL and hGH levels due to an hPRL and hGH producing adenoma, all patients had normal hPRL responses to TRH. In those with inactive acromegaly, 9 had hPRL levels below normal and only , out of the 15 patients showed a normal rise of hPRL after TRH. The patients who showed no hPRL response to TRH demonstrated also other signs of pituitary insufficiency due to the operative procedure. In contrast to a previous report these findings demonstrate that normal or enhanced hPRL secretion is found in active acromegaly. The inappropriate rise of hGH after TRH is compatible with a loss of specificity of the receptor for GRH of the adenoma cell and can be found also in patients with normal basal hGH levels after treatment suggesting that remaining adenoma tissue is present in the pituitary fossa.", "contents": "[Stimulation of growth hormone and prolactin secretion with TRH in acromegaly (author's transl)]. Inappropriate stimulation of growth hormone (hGH)-secretion with TRH in acromegalic subjects has been shown previously, whereas prolactin (hPRL) secretion was reported to be blunted in active acromegaly. In this study TRH induced hGH and hPRL secretion was investigated in 23 active (mean hGH level: 68.5 +/- 19.9 ng/ml; +/- SE) and 15 inactive acromegalics (mean hGH level: 2.3 +/- 0.4 ng/ml; +/- SE). Fourteen of the active acromegalics showed a significant increase up to more than double of the basal hGH level after 200 mug TRH while in only one of the inactive acromegalics an inappropriate rise of hGH was induced by TRH. Basal hPRL levels were elevated in 9 and within normal range in 14 of the patients with active acromegaly. Except in 3 patients who had normal basal hPRL levels and in one patient with excessively elevated hPRL and hGH levels due to an hPRL and hGH producing adenoma, all patients had normal hPRL responses to TRH. In those with inactive acromegaly, 9 had hPRL levels below normal and only , out of the 15 patients showed a normal rise of hPRL after TRH. The patients who showed no hPRL response to TRH demonstrated also other signs of pituitary insufficiency due to the operative procedure. In contrast to a previous report these findings demonstrate that normal or enhanced hPRL secretion is found in active acromegaly. The inappropriate rise of hGH after TRH is compatible with a loss of specificity of the receptor for GRH of the adenoma cell and can be found also in patients with normal basal hGH levels after treatment suggesting that remaining adenoma tissue is present in the pituitary fossa."} {"id": "PMID:177806", "title": "Plasma alkaline phosphatase in mice with experimentally-induced osteosarcomas.", "content": "No statistically significant difference in alkaline phosphatase levels was demonstrated in animals injected with the FBJ virus. However, there was a significant increase associated with the development of osteosarcomas in response to the iv injection of 1.0 uCi 90 Sr/g body weight into 11-18-mo-old Anl:CFl females. It was proposed that alkaline phosphatase determinations can be used as well as roentenographic analysis to detect 90Sr-induced tumors in mice.", "contents": "Plasma alkaline phosphatase in mice with experimentally-induced osteosarcomas. No statistically significant difference in alkaline phosphatase levels was demonstrated in animals injected with the FBJ virus. However, there was a significant increase associated with the development of osteosarcomas in response to the iv injection of 1.0 uCi 90 Sr/g body weight into 11-18-mo-old Anl:CFl females. It was proposed that alkaline phosphatase determinations can be used as well as roentenographic analysis to detect 90Sr-induced tumors in mice."} {"id": "PMID:177807", "title": "Multiple testing for the detection of B virus antibody in specially handled rhesus monkeys after capture from virgin trapping grounds.", "content": "Eight groups of rhesus monkeys totaling over 1,000 animals were captured in the virgin trapping grounds of Jammu and Kashmir, India. Individual caging and special handling technics were utilized to prevent cross-contamination during capture, holding, and subsequent shipment to quarantine facilities in the United States. Immediately following the arrival of the monkeys, 5 consecutive blood samples were obtained at approximately 2-wk intervals, and the sera were rested for neutralizing antibody against Herpesvirus simiae. In order to assure the greatest sensitivity possible, sera were not heat-inactivated and were tested against only 10 TCID50 units of virus in addition to the more commonly used concentration of 100 TCID50 units. The first test detected 80-90% of the positive animals within each group, and only 1 seroconversion was noted after the second test. Seventy-three percent of the adults, 36.6% of the young adults, and 12.4% of the juvenile macaques were found to be antibody-positive. Considering the measures employed to prevent cross contamination, these percentages probably reflect the true prevalence of B virus infection in these rhesus monkeys at the time of their capture in the wild.", "contents": "Multiple testing for the detection of B virus antibody in specially handled rhesus monkeys after capture from virgin trapping grounds. Eight groups of rhesus monkeys totaling over 1,000 animals were captured in the virgin trapping grounds of Jammu and Kashmir, India. Individual caging and special handling technics were utilized to prevent cross-contamination during capture, holding, and subsequent shipment to quarantine facilities in the United States. Immediately following the arrival of the monkeys, 5 consecutive blood samples were obtained at approximately 2-wk intervals, and the sera were rested for neutralizing antibody against Herpesvirus simiae. In order to assure the greatest sensitivity possible, sera were not heat-inactivated and were tested against only 10 TCID50 units of virus in addition to the more commonly used concentration of 100 TCID50 units. The first test detected 80-90% of the positive animals within each group, and only 1 seroconversion was noted after the second test. Seventy-three percent of the adults, 36.6% of the young adults, and 12.4% of the juvenile macaques were found to be antibody-positive. Considering the measures employed to prevent cross contamination, these percentages probably reflect the true prevalence of B virus infection in these rhesus monkeys at the time of their capture in the wild."} {"id": "PMID:177808", "title": "Experimental viral infections of the inner ear. I. Acute infections of the newborn hamster labyrinth.", "content": "Acute viral infections of the inner ear were produced in neonatal hamsters. Viruses were inoculated percutaneously through the temporal cartilage into the endolymphatic and perilymphatic spaces of the labyrinth or were inoculated intracerebrally to reach the perilymphatic spaces via the cochlear aqueduct. Selective vulnerability of inner ear structures was demonstrated using a variety of viruses. Influenza virus infected only the mesenchymal cells of the perilymphatic channels of the cochlea; mumps virus infected principally endolymphatic structures; herpes simplex virus infected primarily the sensory cells of the labyrinth; and rubeola and vaccinia viruses infected both perilymphatic and endolymphatic cells.", "contents": "Experimental viral infections of the inner ear. I. Acute infections of the newborn hamster labyrinth. Acute viral infections of the inner ear were produced in neonatal hamsters. Viruses were inoculated percutaneously through the temporal cartilage into the endolymphatic and perilymphatic spaces of the labyrinth or were inoculated intracerebrally to reach the perilymphatic spaces via the cochlear aqueduct. Selective vulnerability of inner ear structures was demonstrated using a variety of viruses. Influenza virus infected only the mesenchymal cells of the perilymphatic channels of the cochlea; mumps virus infected principally endolymphatic structures; herpes simplex virus infected primarily the sensory cells of the labyrinth; and rubeola and vaccinia viruses infected both perilymphatic and endolymphatic cells."} {"id": "PMID:177809", "title": "The induction of emphysema with elastase. II. Changes in connective tissue.", "content": "Both clinical and experimental evidence implicate proteolytic enzymes active against elastin in the pathogenesis of emphysema. Paradoxically, however, the elastin content of emphysematous human lungs at autopsy has been normal. When emphysema was produced in hamsters by a single intratracheal injection of 25 units of porcine pancreatic elastase, the elastin content of the lungs was reduced from 1.40 +/- 0.22 mg. in controls to 0.43 +/- 0.10 mg. 24 hours after injection, and histologic sections showed that many elastic fibers had disappeared. The elastin content of the lungs gradually increased, approaching normal values by 2 months after injection. The incorporation of 14C-proline into elastin was markedly elevated during the first 2 weeks after injection, decreasing nearly to normal by 2 months. The synthesis of collagen was also increased, indicated by an increase in the collagen content of the lung, an increase in the prolyl hydroxylase activity, and an increase in incorporation of labeled proline into collagen. During the period of active resynthesis of elastin, small clumps of microfibrils and elastic fibrils were visible by electron microscopy within grooves on the surface of septal connective tissue cells in the lungs. Many elastic fibers seen in histologic sections up to 4 months after injection were of abnormal configuration and disorganized.", "contents": "The induction of emphysema with elastase. II. Changes in connective tissue. Both clinical and experimental evidence implicate proteolytic enzymes active against elastin in the pathogenesis of emphysema. Paradoxically, however, the elastin content of emphysematous human lungs at autopsy has been normal. When emphysema was produced in hamsters by a single intratracheal injection of 25 units of porcine pancreatic elastase, the elastin content of the lungs was reduced from 1.40 +/- 0.22 mg. in controls to 0.43 +/- 0.10 mg. 24 hours after injection, and histologic sections showed that many elastic fibers had disappeared. The elastin content of the lungs gradually increased, approaching normal values by 2 months after injection. The incorporation of 14C-proline into elastin was markedly elevated during the first 2 weeks after injection, decreasing nearly to normal by 2 months. The synthesis of collagen was also increased, indicated by an increase in the collagen content of the lung, an increase in the prolyl hydroxylase activity, and an increase in incorporation of labeled proline into collagen. During the period of active resynthesis of elastin, small clumps of microfibrils and elastic fibrils were visible by electron microscopy within grooves on the surface of septal connective tissue cells in the lungs. Many elastic fibers seen in histologic sections up to 4 months after injection were of abnormal configuration and disorganized."} {"id": "PMID:177813", "title": "ATP-stimulated transmitter release and cyclic AMP synthesis in isolated chromaffin granules.", "content": "ATP stimulates chromaffin granules from the bovine adrenal medulla to release epinephrine and specific soluble proteins. ATP analogs substituted in the beta-gamma position with either nitrogen or carbon were also found to be effective at inducing release from isolated chromaffin granules. However, an ATP analog substituted at the alpha-beta position with carbon was strongly inhibitory. Cyclic AMP was also found to be synthesized by isolated chromaffin granules under release conditions. ATP analogs were effective as substrates for adenylate cyclase in the same order as their efficiency for inducing release from vesicles. Hydrolysis at the beta-gamma linkage of ATP therefore is probably not necessary for release; however, hydrolysis at the alpha-beta position may be important in the release process. Cyclic AMP may be produced and play a regulatory role in this event.", "contents": "ATP-stimulated transmitter release and cyclic AMP synthesis in isolated chromaffin granules. ATP stimulates chromaffin granules from the bovine adrenal medulla to release epinephrine and specific soluble proteins. ATP analogs substituted in the beta-gamma position with either nitrogen or carbon were also found to be effective at inducing release from isolated chromaffin granules. However, an ATP analog substituted at the alpha-beta position with carbon was strongly inhibitory. Cyclic AMP was also found to be synthesized by isolated chromaffin granules under release conditions. ATP analogs were effective as substrates for adenylate cyclase in the same order as their efficiency for inducing release from vesicles. Hydrolysis at the beta-gamma linkage of ATP therefore is probably not necessary for release; however, hydrolysis at the alpha-beta position may be important in the release process. Cyclic AMP may be produced and play a regulatory role in this event."} {"id": "PMID:177814", "title": "DNA synthesis in cultured human fibroblasts: regulation by 3':5'-cyclic AMP.", "content": "The addition of serum to density-inhibited human fibroblast cultures induced a wave of DNA synthesis, measured as [3H] thymidine incorporation into acid-precipitable material, beginning after 8-12 hr and reaching maximum levels of 16-24 hr. Addition of dibutyryl-3':5'-cyclic AMP (DBcAMP) together with serum inhibited [3H] thymidine incorporation by 75-95%. When DBcAMP was added for the first 4 hr of serum stimulation and then removed, the wave of DNA synthesis was not delayed. This suggested that serum could induce DNA synthesis even though cyclic AMP concentrations were maintained at high levels by DBcAMP during this initial period. These results are inconsistent with the hypothesis that it is the immediate transient reduction in 3':5'-cyclic AMP concentration following the addition of serum that triggers DNA synthesis. By contrast, DBcAMP added 8 hr after serum inhibited [3H] thymidine incorporation to the same extent as DBcAMP added at the same time as serum. This indicated that a step essential for DNA synthesis and occurring late in G1 was inhibited by high concentrations of 3':5'-cyclic AMP.", "contents": "DNA synthesis in cultured human fibroblasts: regulation by 3':5'-cyclic AMP. The addition of serum to density-inhibited human fibroblast cultures induced a wave of DNA synthesis, measured as [3H] thymidine incorporation into acid-precipitable material, beginning after 8-12 hr and reaching maximum levels of 16-24 hr. Addition of dibutyryl-3':5'-cyclic AMP (DBcAMP) together with serum inhibited [3H] thymidine incorporation by 75-95%. When DBcAMP was added for the first 4 hr of serum stimulation and then removed, the wave of DNA synthesis was not delayed. This suggested that serum could induce DNA synthesis even though cyclic AMP concentrations were maintained at high levels by DBcAMP during this initial period. These results are inconsistent with the hypothesis that it is the immediate transient reduction in 3':5'-cyclic AMP concentration following the addition of serum that triggers DNA synthesis. By contrast, DBcAMP added 8 hr after serum inhibited [3H] thymidine incorporation to the same extent as DBcAMP added at the same time as serum. This indicated that a step essential for DNA synthesis and occurring late in G1 was inhibited by high concentrations of 3':5'-cyclic AMP."} {"id": "PMID:177815", "title": "Insulin binding and glucose transport in the R3230AC mammary adenocarcinoma.", "content": "Cells dissociated from the R3230AC mammary adenocarcinoma from intact and diabetic rats were examined for insulin binding and glucose transport. The Kd for insulin binding, approximately 10(--10) M, was similar in all tumors studied. However, the apparent number of receptor sites per cell increased in cells from diabetic rats. Kinetic analysis of 3-0-methyl glucose (3-OMG) entry showed both diffusional and passive carrier characteristics. Insulin (4 X 10(--9) M) in vitro did not affect diffusional entry, whereas the hormone altered the passive carrier system, as reflected by an increase in Km and Vmax. Insulin decreased initial velocity of glucose transport at 4--6 mM glucose levels but increased initial velocity of glucose transport at 20 mM glucose. An explanation of the role of insulin on tumor growth in vivo from effects on glucose transport in vitro is proposed.", "contents": "Insulin binding and glucose transport in the R3230AC mammary adenocarcinoma. Cells dissociated from the R3230AC mammary adenocarcinoma from intact and diabetic rats were examined for insulin binding and glucose transport. The Kd for insulin binding, approximately 10(--10) M, was similar in all tumors studied. However, the apparent number of receptor sites per cell increased in cells from diabetic rats. Kinetic analysis of 3-0-methyl glucose (3-OMG) entry showed both diffusional and passive carrier characteristics. Insulin (4 X 10(--9) M) in vitro did not affect diffusional entry, whereas the hormone altered the passive carrier system, as reflected by an increase in Km and Vmax. Insulin decreased initial velocity of glucose transport at 4--6 mM glucose levels but increased initial velocity of glucose transport at 20 mM glucose. An explanation of the role of insulin on tumor growth in vivo from effects on glucose transport in vitro is proposed."} {"id": "PMID:177816", "title": "Cooperative properties of hormone receptors in cell membranes.", "content": "The binding of many polypeptide hormones to cell surface receptors does not appear to follow the law of mass action. While steady-state binding data are consistent in many cases with either heterogeneous populations of binding sites or interactions of the type known as negative cooperativity, study of the kinetics of dissociation of the type known as negative cooperativity, study of the kinetics of dissociation of the hormone receptor complex allows an unambiguous demonstration of cooperative interactions. Negative cooperativity, which seems to be wide-spread among hormone receptors, provides exquisite sensitivity of the cell at low hormone concentrations while buffering against acutely elevated hormone levels. The molecular mechanisms underlying the cooperativity are still largely unknown. Cooperativity may stem from a conformational transition in individual receptors or involve receptor aggregation in the fluid membrane (clustering) or more extensive membrane phenomena. Thus, new models of hormone action must be considered which integrate the progress in our knowledge of both the complex mechanisms regulating hormone binding to their surface receptors, and the dynamic properties of the cell membrane.", "contents": "Cooperative properties of hormone receptors in cell membranes. The binding of many polypeptide hormones to cell surface receptors does not appear to follow the law of mass action. While steady-state binding data are consistent in many cases with either heterogeneous populations of binding sites or interactions of the type known as negative cooperativity, study of the kinetics of dissociation of the type known as negative cooperativity, study of the kinetics of dissociation of the hormone receptor complex allows an unambiguous demonstration of cooperative interactions. Negative cooperativity, which seems to be wide-spread among hormone receptors, provides exquisite sensitivity of the cell at low hormone concentrations while buffering against acutely elevated hormone levels. The molecular mechanisms underlying the cooperativity are still largely unknown. Cooperativity may stem from a conformational transition in individual receptors or involve receptor aggregation in the fluid membrane (clustering) or more extensive membrane phenomena. Thus, new models of hormone action must be considered which integrate the progress in our knowledge of both the complex mechanisms regulating hormone binding to their surface receptors, and the dynamic properties of the cell membrane."} {"id": "PMID:177817", "title": "Hormone receptor mobility and catecholamine binding in membranes. A theoretical model.", "content": "[3H]-Catecholamine binding to intact cells, isolated cell membranes, and to several isolated macromolecules has been shown by several laboratories to be neither stereospecific nor inhibited by known beta-antagonists. Since additional evidence indicates that this binding is not an artifact (i.e. due neither to the binding of a catecholamine oxidation product nor hormone binding to a catabolic enzyme such as COMT), the question remains as to whether this represents binding to a bona fide membrane receptor. Because all ligands which bind strongly or compete for this binding possess a catechol group, one possible explanation is that the binding affinity is primarily determined by the catechol moiety, whereas the correct stereoisomer of the side chain is necessary to activate the receptor. Thus, although binding is a necessary condition for hormone action, the necessary and sufficient condition for activation of adenyl cyclase is both the catechol group and the correct stereoisomer of the side chain. A theoretical model is developed here to provide a quantitative basis for this hypothesis. This model extends the current concept of distinct subunits in the adenyl cyclase system by separating the receptors from the catalytic sites and placing them at separate locations within the membrane. Utilizing the spare receptor model of Furchgott, and the mobility of macromolecules within a \"lipid sea,\" the appropriate equations to predict both hormone binding and enzyme activation are derived. Using the observed affinity constants from catecholamine binding studies, it is then shown that this model can predict the experimental observation and hence explain the apparent dichotomy arising from binding enzyme activation studies.", "contents": "Hormone receptor mobility and catecholamine binding in membranes. A theoretical model. [3H]-Catecholamine binding to intact cells, isolated cell membranes, and to several isolated macromolecules has been shown by several laboratories to be neither stereospecific nor inhibited by known beta-antagonists. Since additional evidence indicates that this binding is not an artifact (i.e. due neither to the binding of a catecholamine oxidation product nor hormone binding to a catabolic enzyme such as COMT), the question remains as to whether this represents binding to a bona fide membrane receptor. Because all ligands which bind strongly or compete for this binding possess a catechol group, one possible explanation is that the binding affinity is primarily determined by the catechol moiety, whereas the correct stereoisomer of the side chain is necessary to activate the receptor. Thus, although binding is a necessary condition for hormone action, the necessary and sufficient condition for activation of adenyl cyclase is both the catechol group and the correct stereoisomer of the side chain. A theoretical model is developed here to provide a quantitative basis for this hypothesis. This model extends the current concept of distinct subunits in the adenyl cyclase system by separating the receptors from the catalytic sites and placing them at separate locations within the membrane. Utilizing the spare receptor model of Furchgott, and the mobility of macromolecules within a \"lipid sea,\" the appropriate equations to predict both hormone binding and enzyme activation are derived. Using the observed affinity constants from catecholamine binding studies, it is then shown that this model can predict the experimental observation and hence explain the apparent dichotomy arising from binding enzyme activation studies."} {"id": "PMID:177818", "title": "Regulation of SV40-induced cell division and tumor antigen by dibutyryl adenosine 3'-5'-monophosphate.", "content": "Simian virus 40 (SV40) induces cell division in microcultures of sparsely plated nongrowing mouse BALB/3T3 cells during acute infection at moderate multiplicities of infection (MOI = 10-100). The infected cells are killed when a MOI of 1,000 is used. SV40 tumor (T) antigen is synthesized in the infected cells, but viral DNA, virion antigen, and progeny virions are not synthesized (abortive infection). The addition of exogenous dibutyryl adenosine 3'-5'-monophosphate (dbcAMP) at the time of infection stimulates the SV40-induced cell division at all MOI and inhibits SV40-induced cell death at high MOI. The percentage of T antigen-positive cells, as monitored by immunofluorescence, is also increased by the addition of dbcAMP at the time of infection. This regulation of SV40-induced cell division and T antigen formation by exogenous dbcAMP occurs within the first 6 hr after infection at 37 degrees C and is dependent upon both the MOI and the concentration of added dbcAMP. The addition of dbcAMP to productively infected TC7 monkey cells has litte effect on the SV40-induced cell death or T antigen formation.", "contents": "Regulation of SV40-induced cell division and tumor antigen by dibutyryl adenosine 3'-5'-monophosphate. Simian virus 40 (SV40) induces cell division in microcultures of sparsely plated nongrowing mouse BALB/3T3 cells during acute infection at moderate multiplicities of infection (MOI = 10-100). The infected cells are killed when a MOI of 1,000 is used. SV40 tumor (T) antigen is synthesized in the infected cells, but viral DNA, virion antigen, and progeny virions are not synthesized (abortive infection). The addition of exogenous dibutyryl adenosine 3'-5'-monophosphate (dbcAMP) at the time of infection stimulates the SV40-induced cell division at all MOI and inhibits SV40-induced cell death at high MOI. The percentage of T antigen-positive cells, as monitored by immunofluorescence, is also increased by the addition of dbcAMP at the time of infection. This regulation of SV40-induced cell division and T antigen formation by exogenous dbcAMP occurs within the first 6 hr after infection at 37 degrees C and is dependent upon both the MOI and the concentration of added dbcAMP. The addition of dbcAMP to productively infected TC7 monkey cells has litte effect on the SV40-induced cell death or T antigen formation."} {"id": "PMID:177819", "title": "Cyclic nucleotides and cell growth.", "content": "Growth induction in resting fibroblast cultures by serum or growth factors induces a fast, transient cGMP peak which may constitute the intracellular signal for growth. A similar cGMP peak occurs when 3T3 cells arrested at the restriction point or in G0 by starvation for certain amino acids are induced for growth by readdition of the lacking nutrients. Both 3T3 and SV3T3 cells which are arrested randomly all around the cell cycle do not exhibit major changes in cyclic nucleotides after growth induction. Determination of intracellular cAMP and cGMP levels in normal and transformed fibroblasts under different growth conditions shows that the transition between growing and resting state (G0 arrest) is accompanied and probably induced by characteristic changes in cAMP to cGMP ratios. cGMP is decreased 2-5-fold in resting as compared to growing cultures, and increased 10-20-fold in activated cultures 20 min after serum induction. No major cGMP change was observed in growing, confluent, or serum-activated cultures of transformed cells. Measurement of guanylcyclase under unphysiological conditions (2 mM Mn++) in crude and purified membranes from 3T3 and SV3T3 cultures did not show increased enzyme activity in the transformed cells. Significant differences may only show up when synchronized cells pass through the restriction point in G1 phase. As a hypothesis it is proposed that transformed cells have an activated guanylcyclase system or a relaxed cGMP-pleiotypic response mechanism at the restriction point of their cell cycle.", "contents": "Cyclic nucleotides and cell growth. Growth induction in resting fibroblast cultures by serum or growth factors induces a fast, transient cGMP peak which may constitute the intracellular signal for growth. A similar cGMP peak occurs when 3T3 cells arrested at the restriction point or in G0 by starvation for certain amino acids are induced for growth by readdition of the lacking nutrients. Both 3T3 and SV3T3 cells which are arrested randomly all around the cell cycle do not exhibit major changes in cyclic nucleotides after growth induction. Determination of intracellular cAMP and cGMP levels in normal and transformed fibroblasts under different growth conditions shows that the transition between growing and resting state (G0 arrest) is accompanied and probably induced by characteristic changes in cAMP to cGMP ratios. cGMP is decreased 2-5-fold in resting as compared to growing cultures, and increased 10-20-fold in activated cultures 20 min after serum induction. No major cGMP change was observed in growing, confluent, or serum-activated cultures of transformed cells. Measurement of guanylcyclase under unphysiological conditions (2 mM Mn++) in crude and purified membranes from 3T3 and SV3T3 cultures did not show increased enzyme activity in the transformed cells. Significant differences may only show up when synchronized cells pass through the restriction point in G1 phase. As a hypothesis it is proposed that transformed cells have an activated guanylcyclase system or a relaxed cGMP-pleiotypic response mechanism at the restriction point of their cell cycle."} {"id": "PMID:177820", "title": "Vasopressin-sensitive kidney adenylate cyclase: modulation of the hormonal response.", "content": "Vasopressin-sensitive pig kidney adenylate cyclase is sensitive to several effectors, such as Mg2+, other divalent cations, and guanyl nucleotides. The purpose of the present study was to compare the main characteristics of adenylate cyclase activation by vasopressin, Mg2+, and GMPPNP, respectively. Mg2+ ions were shown to exert at least three different effects on adenylate cyclase. The substrate of the adenylate cyclase reaction is the Mg-ATP complex. Mg2+ interacts with an enzyme regulatory site. Finally, Mg2+ can modulate the hormonal response, with Mg2+ ions affecting the coupling function--that is, the quantitative relationship between receptor occupancy and adenylate cyclase activation. At all the magnesium concentrations tested, from 0.25 mM to 16 mM, adenylate cyclase activation was not a direct function of receptor occupancy. At low Mg2+ concentrations, adenylate cyclase activation dose-response curve to the hormone tended to be superimposable to the hormone dose-binding curve. These results suggest a role of magnesium at the coupling step between the hormone-receptor complex and adenylate cyclase response. Cobalt, but not calcium, ions could exert the same effects as Mg2+ ions on this coupling step. GMPPNP induced considerable adenylate cyclase activation (15 to 35 times the basal value). Activation by GMPPNP was highly time and temperature dependent. At 30 degrees C, a 20 to 60 min preincubation period in the presence of GMPPNP was needed to obtain maximal activation. The higher the dose of GMPPNP in the medium, the longer it took to reach equilibrium. At 15 degrees C, activation was still increasing with time after 3 hr preincubation in the presence of the nucleotide. GMPPNP was active in a 10(-8)M to 10(-5)M concentration range. Unlike the results obtained with lysine vasopressin, the kinetic characteristics of dose-dependent adenylate cyclase activation curves by GMPPNP were unaffected by varying Mg2+ concentrations except for the increase in velocity when raising Mg2+ concentration. It was not clear whether or not the activation processes by the hormone and by GMPPNP had common mechanisms.", "contents": "Vasopressin-sensitive kidney adenylate cyclase: modulation of the hormonal response. Vasopressin-sensitive pig kidney adenylate cyclase is sensitive to several effectors, such as Mg2+, other divalent cations, and guanyl nucleotides. The purpose of the present study was to compare the main characteristics of adenylate cyclase activation by vasopressin, Mg2+, and GMPPNP, respectively. Mg2+ ions were shown to exert at least three different effects on adenylate cyclase. The substrate of the adenylate cyclase reaction is the Mg-ATP complex. Mg2+ interacts with an enzyme regulatory site. Finally, Mg2+ can modulate the hormonal response, with Mg2+ ions affecting the coupling function--that is, the quantitative relationship between receptor occupancy and adenylate cyclase activation. At all the magnesium concentrations tested, from 0.25 mM to 16 mM, adenylate cyclase activation was not a direct function of receptor occupancy. At low Mg2+ concentrations, adenylate cyclase activation dose-response curve to the hormone tended to be superimposable to the hormone dose-binding curve. These results suggest a role of magnesium at the coupling step between the hormone-receptor complex and adenylate cyclase response. Cobalt, but not calcium, ions could exert the same effects as Mg2+ ions on this coupling step. GMPPNP induced considerable adenylate cyclase activation (15 to 35 times the basal value). Activation by GMPPNP was highly time and temperature dependent. At 30 degrees C, a 20 to 60 min preincubation period in the presence of GMPPNP was needed to obtain maximal activation. The higher the dose of GMPPNP in the medium, the longer it took to reach equilibrium. At 15 degrees C, activation was still increasing with time after 3 hr preincubation in the presence of the nucleotide. GMPPNP was active in a 10(-8)M to 10(-5)M concentration range. Unlike the results obtained with lysine vasopressin, the kinetic characteristics of dose-dependent adenylate cyclase activation curves by GMPPNP were unaffected by varying Mg2+ concentrations except for the increase in velocity when raising Mg2+ concentration. It was not clear whether or not the activation processes by the hormone and by GMPPNP had common mechanisms."} {"id": "PMID:177821", "title": "Breast masses in males with carcinoma of the prostate.", "content": "Breast masses in male patients who have prostatic carcinoma may represent gynecomastia secondary to estrogen therapy, metastasis of the prostatic carcinoma to the breast, or a primary carcinoma of the breast. Accurate diagnosis of this lesion by biopsy and, if possible, histochemical determination of acid phosphatase is essential to determine prognosis and treatment. The patient with breast metastases from a primary prostatic carcinoma will survive on the average only 4 mo. However, in the patient with prostatic carcinoma, surgical treatment for a primary breast carcinoma may extend survival considerably.", "contents": "Breast masses in males with carcinoma of the prostate. Breast masses in male patients who have prostatic carcinoma may represent gynecomastia secondary to estrogen therapy, metastasis of the prostatic carcinoma to the breast, or a primary carcinoma of the breast. Accurate diagnosis of this lesion by biopsy and, if possible, histochemical determination of acid phosphatase is essential to determine prognosis and treatment. The patient with breast metastases from a primary prostatic carcinoma will survive on the average only 4 mo. However, in the patient with prostatic carcinoma, surgical treatment for a primary breast carcinoma may extend survival considerably."} {"id": "PMID:177822", "title": "Erythropoietin levels in Wistar-Furth Wilms' tumor rats.", "content": "Erythropoietin (ESF) levels were assayed in rats bearing the Wistar-Furth Wilms' transplantable tumor. Sites of tumor inoculation varied from subcutaneous, intramuscular, intrarenal (subcapsular), to intraperitoneal. Two-thirds of the animals exhibited ESF elevations without polycythemia, or severe anemia (HCT less than 30.0 vol%). The elevations of ESF were not detectably related to the time of sacrifice (age of the animal), size of the primary tumor, or number of gross metastatic foci. The diminished ESF response noted to animals given intramuscular tumor implantations is believed to reflect differences in tumor blood and lymphatic supply at the various sites of inoculation. The pattern of ESF responses in the Wistar-Furth Wilms' tumor model is thus quite similar to that which we have observed in man, and appears to represent an animal model for tumor-related ectopic hormone release. The nature of the hormone is believed to differ from that seen in normal physiological states.", "contents": "Erythropoietin levels in Wistar-Furth Wilms' tumor rats. Erythropoietin (ESF) levels were assayed in rats bearing the Wistar-Furth Wilms' transplantable tumor. Sites of tumor inoculation varied from subcutaneous, intramuscular, intrarenal (subcapsular), to intraperitoneal. Two-thirds of the animals exhibited ESF elevations without polycythemia, or severe anemia (HCT less than 30.0 vol%). The elevations of ESF were not detectably related to the time of sacrifice (age of the animal), size of the primary tumor, or number of gross metastatic foci. The diminished ESF response noted to animals given intramuscular tumor implantations is believed to reflect differences in tumor blood and lymphatic supply at the various sites of inoculation. The pattern of ESF responses in the Wistar-Furth Wilms' tumor model is thus quite similar to that which we have observed in man, and appears to represent an animal model for tumor-related ectopic hormone release. The nature of the hormone is believed to differ from that seen in normal physiological states."} {"id": "PMID:177825", "title": "Epicardial tumor-like angiofibromatous proliferative lesion. An unusual complication of coronary bypass surgery.", "content": "The first report of an unusual complication of coronary bypass surgery for myocardial revascularization is presented. In a dog used for experimental studies of internal mammary artery (IMA)-coronary bypass and killed three months later, the postmortem examination of the heart showed a tumor-like epicardial angiofibromatous nodule at the site of the IMA-left anterior descending (LAD) coronary artery anastomosis. The lesion, consisting of plexiform vascular channels in a fibrocollagenous stroma, measured 2 by 1.5 by 1 cm. This was the only lesion found in the animal. It was speculated that the lesion might have arisen from a hematoma developing at the site of arterial anastomosis.", "contents": "Epicardial tumor-like angiofibromatous proliferative lesion. An unusual complication of coronary bypass surgery. The first report of an unusual complication of coronary bypass surgery for myocardial revascularization is presented. In a dog used for experimental studies of internal mammary artery (IMA)-coronary bypass and killed three months later, the postmortem examination of the heart showed a tumor-like epicardial angiofibromatous nodule at the site of the IMA-left anterior descending (LAD) coronary artery anastomosis. The lesion, consisting of plexiform vascular channels in a fibrocollagenous stroma, measured 2 by 1.5 by 1 cm. This was the only lesion found in the animal. It was speculated that the lesion might have arisen from a hematoma developing at the site of arterial anastomosis."} {"id": "PMID:177827", "title": "Quality-of-care assessment. I. Outpatient management of acute bacterial cystitis as the model.", "content": "A study was undertaken to determine whether a process audit of outpatient medical care would correlate significantly with the outcomes of care and thus prove to be a valid method for assessing the quality of medical care in the outpatient setting. Acute bacterial cystitis in women was selected as the model for study. A series of 42 cases was reviewed by retrospective analysis of patient records supplemented by follow-up interviews and collection of a follow-up urine culture from each patient to document the outcome of treatment. No positive association was demonstrated between the processes for satisfactory care selected by the expert criteria committee and the observed outcomes. Reasons for this failure in the present study and for deficiencies of the process audit method in general are discussed.", "contents": "Quality-of-care assessment. I. Outpatient management of acute bacterial cystitis as the model. A study was undertaken to determine whether a process audit of outpatient medical care would correlate significantly with the outcomes of care and thus prove to be a valid method for assessing the quality of medical care in the outpatient setting. Acute bacterial cystitis in women was selected as the model for study. A series of 42 cases was reviewed by retrospective analysis of patient records supplemented by follow-up interviews and collection of a follow-up urine culture from each patient to document the outcome of treatment. No positive association was demonstrated between the processes for satisfactory care selected by the expert criteria committee and the observed outcomes. Reasons for this failure in the present study and for deficiencies of the process audit method in general are discussed."} {"id": "PMID:177830", "title": "Macrobodies in chick blastoderm.", "content": "The results of this study show that the epiblast cells of chick blastoderm at Hamburger-Hamilton stage 1 contain macrobodies which themselves contain particles resembling the 'lining bodies' described by Bellairs. Since different structures ranging from macrobodies to light vacuoles have been found, it seems probable that their contents are utilized at this stage. Typically, they are surrounded by mitochondria, some of which have an abnormal internal structure. At later developmental stages neither macrobodies nor abnormal mitochondria were observed.", "contents": "Macrobodies in chick blastoderm. The results of this study show that the epiblast cells of chick blastoderm at Hamburger-Hamilton stage 1 contain macrobodies which themselves contain particles resembling the 'lining bodies' described by Bellairs. Since different structures ranging from macrobodies to light vacuoles have been found, it seems probable that their contents are utilized at this stage. Typically, they are surrounded by mitochondria, some of which have an abnormal internal structure. At later developmental stages neither macrobodies nor abnormal mitochondria were observed."} {"id": "PMID:177831", "title": "Lowering appointment failures in a neighborhood health center.", "content": "Failure to keep appointments constitutes a barrier to the delivery of continuous care in many comprehensive health care facilities. At a neighborhood health center in Pittsburgh, Pa., 336 appointments were studied to determine whether reminder letters or reminder calls could improve compliance with appointments scheduled more than three weeks in advance. The failure rate in the control group was 38 per cent compared with 10 per cent for the letter reminder group and 9 per cent for the telephone reminder group. The differences in kept, cancelled, and failed rates between letter and telephone groups were not statistically significant (p greater than .05). The kept rate increased with patient's age in all three groups. Complicance was not affected by sex of the patient, length of time that appointment was scheduled in advance, or day of the week. Compliance was greatest among appointments scheduled for chronic illness follow-up and physical examinations, and least among appointments scheduled for \"screening.\"", "contents": "Lowering appointment failures in a neighborhood health center. Failure to keep appointments constitutes a barrier to the delivery of continuous care in many comprehensive health care facilities. At a neighborhood health center in Pittsburgh, Pa., 336 appointments were studied to determine whether reminder letters or reminder calls could improve compliance with appointments scheduled more than three weeks in advance. The failure rate in the control group was 38 per cent compared with 10 per cent for the letter reminder group and 9 per cent for the telephone reminder group. The differences in kept, cancelled, and failed rates between letter and telephone groups were not statistically significant (p greater than .05). The kept rate increased with patient's age in all three groups. Complicance was not affected by sex of the patient, length of time that appointment was scheduled in advance, or day of the week. Compliance was greatest among appointments scheduled for chronic illness follow-up and physical examinations, and least among appointments scheduled for \"screening.\""} {"id": "PMID:177832", "title": "Basis and some diagnostic implications of electrocochleography.", "content": "Electrocochleography (ECoG) involves the recording of electrical responses to sound from the vicinity of the cochlea. The technique, as we practice it, utilizes a trans-tympanic recording needle situated on the promontory of the middle ear. Filtered clicks in the frequency range between 500 and 8,000 Hz are presented to the ear under test at a rate of 10/sec. Repetitive clicks of a given frequency are first presented at high intensity and the responses summed (averaged) in a computer. The click is systematically lowered in intensity, and an average is collected at each level until the normal dynamic range of hearing has been explored. Two major electrical indices are present in the recording: these are 1. the whole-nerve action potential (AP) derived from the first-order auditory neurons, and 2. the cochlear microphonic (CM) derived from the hair cells. Inspection of the whole nerve AP as intensity is lowered allows the estimation of the response threshold, which correlates well with behavioral threshold. Inspection of the relation between the CM and the AP allows qualitative differentiation to be made between pathology arising in the hair cell (sensory) and in the nerve (neural).", "contents": "Basis and some diagnostic implications of electrocochleography. Electrocochleography (ECoG) involves the recording of electrical responses to sound from the vicinity of the cochlea. The technique, as we practice it, utilizes a trans-tympanic recording needle situated on the promontory of the middle ear. Filtered clicks in the frequency range between 500 and 8,000 Hz are presented to the ear under test at a rate of 10/sec. Repetitive clicks of a given frequency are first presented at high intensity and the responses summed (averaged) in a computer. The click is systematically lowered in intensity, and an average is collected at each level until the normal dynamic range of hearing has been explored. Two major electrical indices are present in the recording: these are 1. the whole-nerve action potential (AP) derived from the first-order auditory neurons, and 2. the cochlear microphonic (CM) derived from the hair cells. Inspection of the whole nerve AP as intensity is lowered allows the estimation of the response threshold, which correlates well with behavioral threshold. Inspection of the relation between the CM and the AP allows qualitative differentiation to be made between pathology arising in the hair cell (sensory) and in the nerve (neural)."} {"id": "PMID:177833", "title": "Aspiration cytology of salivary gland tumors: diagnostic experience from six years of routine laboratory work.", "content": "Fine-needle aspiration cytology has been used as a routine diagnostic instrument in patients with salivary gland lesions during 1966-1972. A retrospective analysis of the primary cytologic reports correlated with the revised final diagnoses in 461 patients where a pathologic report is available, shows exact agreement in 63 percent, good and not misleading agreement in a further 18 percent, while false reports were initially given in 8 percent, and unsatisfactory specimens were obtained in 11 percent of the patients. On revision of the false reports it is found that with the present experience acquired over several years these can be reduced to under 5 percent. This analysis has also given indications upon which types of specimens are likely to cause diagnostic difficulties.", "contents": "Aspiration cytology of salivary gland tumors: diagnostic experience from six years of routine laboratory work. Fine-needle aspiration cytology has been used as a routine diagnostic instrument in patients with salivary gland lesions during 1966-1972. A retrospective analysis of the primary cytologic reports correlated with the revised final diagnoses in 461 patients where a pathologic report is available, shows exact agreement in 63 percent, good and not misleading agreement in a further 18 percent, while false reports were initially given in 8 percent, and unsatisfactory specimens were obtained in 11 percent of the patients. On revision of the false reports it is found that with the present experience acquired over several years these can be reduced to under 5 percent. This analysis has also given indications upon which types of specimens are likely to cause diagnostic difficulties."} {"id": "PMID:177829", "title": "The development of sex differences in the adrenal morphology and responsiveness in stress of rats from birth to the end of life.", "content": "The appearance and development of sex difference in the adrenal cortex of rats have been studied. Morphological and secretory differences between the adrenal cortex of female and male rats begin on the 40th day of postnatal life, when females respond in stress by a greater increase in plasma corticosterone concentration. The sex difference becomes fully manifest at the age of 55 days (females have heavier absolute and relative adrenal glands and respond to stressful stimuli by a greater increase in adrenal and plasma corticosterone concentrations). At the age of 11 to 23 months the adrenal corticosterone concentrations in stress are equal in both sexes, and the absolute adrenal weights are similar from 18.5 months until death. The body weight gain is equal in both sexes during the first 50 days of life and greater in males from day 50 to 1 year of age. After this age the body weight of males remains almost the same (315 to 322 g)8 while females continue gaining weight until the end of life (196 to 231 g). This possible causal relationship between the rhythm of growth and sex difference in the adrenal glands in rats is discussed.", "contents": "The development of sex differences in the adrenal morphology and responsiveness in stress of rats from birth to the end of life. The appearance and development of sex difference in the adrenal cortex of rats have been studied. Morphological and secretory differences between the adrenal cortex of female and male rats begin on the 40th day of postnatal life, when females respond in stress by a greater increase in plasma corticosterone concentration. The sex difference becomes fully manifest at the age of 55 days (females have heavier absolute and relative adrenal glands and respond to stressful stimuli by a greater increase in adrenal and plasma corticosterone concentrations). At the age of 11 to 23 months the adrenal corticosterone concentrations in stress are equal in both sexes, and the absolute adrenal weights are similar from 18.5 months until death. The body weight gain is equal in both sexes during the first 50 days of life and greater in males from day 50 to 1 year of age. After this age the body weight of males remains almost the same (315 to 322 g)8 while females continue gaining weight until the end of life (196 to 231 g). This possible causal relationship between the rhythm of growth and sex difference in the adrenal glands in rats is discussed."} {"id": "PMID:177835", "title": "Hypolipidemic principles of Cicer arietinum: biochanin-A and formononetin.", "content": "Two isoflavones, biochanin-A and formononetin isolated from gram Cicer arietinum, have been shown to possess hypolipidemic properties for Triton WR-1339 induced hyperlipidemia in male albino rats, when administered as a crude extract or as individual compounds.", "contents": "Hypolipidemic principles of Cicer arietinum: biochanin-A and formononetin. Two isoflavones, biochanin-A and formononetin isolated from gram Cicer arietinum, have been shown to possess hypolipidemic properties for Triton WR-1339 induced hyperlipidemia in male albino rats, when administered as a crude extract or as individual compounds."} {"id": "PMID:177836", "title": "Oxidation of N-methyl-gamma-tocopheramine to a nitroxide.", "content": "An unstable nitroxide identified by electron paramagnetic resonance spectra was obtained by oxidation of N-methyl-gamma-tocopheramine with peroxide and also by ultraviolet photooxidation.", "contents": "Oxidation of N-methyl-gamma-tocopheramine to a nitroxide. An unstable nitroxide identified by electron paramagnetic resonance spectra was obtained by oxidation of N-methyl-gamma-tocopheramine with peroxide and also by ultraviolet photooxidation."} {"id": "PMID:177839", "title": "Adenosine 3',5'-monophosphate and the regulation of rat hepatic sterol synthesis: a reexamination based on Sutherland criteria.", "content": "Many investigators have reported that adenosine 3',5'-monophosphate (cyclic AMP) at supraphysiologic concentrations (10(-4) M) suppresses lipogenesis in rat livers in vitro. The data in this report demonstrate that the phosphodiesterase inhibitor theophylline does not suppress sterol synthesis by itself nor does it potentiate the cyclic AMP-mediated suppression. In addition the cyclic AMP-mediated effect was not specific as many structurally-related compounds including adenosine triphosphate, adenosine 5'-diphosphate, adenosine 5'-monophosphate, adenosine, coenzyme A, HMG coenzyme A, and guanosine 3',5'-monophosphate suppressed sterol synthesis. The phenomenon of cyclic AMP-suppression of sterol synthesis does not fulfill two of the four criteria defined by Sutherland to assess whether a given metabolic effect is mediated by cyclic AMP. Therefore, we conclude that the cyclic AMP mediated suppression of sterologenesis is not a physiologic effect of the nucleotide.", "contents": "Adenosine 3',5'-monophosphate and the regulation of rat hepatic sterol synthesis: a reexamination based on Sutherland criteria. Many investigators have reported that adenosine 3',5'-monophosphate (cyclic AMP) at supraphysiologic concentrations (10(-4) M) suppresses lipogenesis in rat livers in vitro. The data in this report demonstrate that the phosphodiesterase inhibitor theophylline does not suppress sterol synthesis by itself nor does it potentiate the cyclic AMP-mediated suppression. In addition the cyclic AMP-mediated effect was not specific as many structurally-related compounds including adenosine triphosphate, adenosine 5'-diphosphate, adenosine 5'-monophosphate, adenosine, coenzyme A, HMG coenzyme A, and guanosine 3',5'-monophosphate suppressed sterol synthesis. The phenomenon of cyclic AMP-suppression of sterol synthesis does not fulfill two of the four criteria defined by Sutherland to assess whether a given metabolic effect is mediated by cyclic AMP. Therefore, we conclude that the cyclic AMP mediated suppression of sterologenesis is not a physiologic effect of the nucleotide."} {"id": "PMID:177840", "title": "Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat.", "content": "In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.", "contents": "Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat. In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity."} {"id": "PMID:177841", "title": "Simultaneous ectopic production of parathyroid hormone and calcitonin.", "content": "Two patients with cancer were evaluated in whom there was evidence for the simultaneous ectopic production of parathyroid hormone (PTH) and calcitonin (CT). One patient had a gastric carcinoid and the other had a pancreatic islet cell carcinoma. Abnormal concentrations of parathyroid hormone and calcitonin were demonstrated by radioimmunoassay in the peripheral blood of each patient and in the gastric tumor. In the pancreatic tumor, immunohistologic studies also demonstrated the presence of CT and PTH and suggested that each hormone was produced by different cells of the tumor. Plasma concentrations of the hormones responded to functional tests of secretion and to tumor chemotherapy. These studies demonstrate the simultaneous ectopic production of the two physiologically antagonistic hormones, PTH and CT, and confirm their value as diagnostic markers for several types of malignancies.", "contents": "Simultaneous ectopic production of parathyroid hormone and calcitonin. Two patients with cancer were evaluated in whom there was evidence for the simultaneous ectopic production of parathyroid hormone (PTH) and calcitonin (CT). One patient had a gastric carcinoid and the other had a pancreatic islet cell carcinoma. Abnormal concentrations of parathyroid hormone and calcitonin were demonstrated by radioimmunoassay in the peripheral blood of each patient and in the gastric tumor. In the pancreatic tumor, immunohistologic studies also demonstrated the presence of CT and PTH and suggested that each hormone was produced by different cells of the tumor. Plasma concentrations of the hormones responded to functional tests of secretion and to tumor chemotherapy. These studies demonstrate the simultaneous ectopic production of the two physiologically antagonistic hormones, PTH and CT, and confirm their value as diagnostic markers for several types of malignancies."} {"id": "PMID:177842", "title": "Acquired increases of human erythrocyte purine enzymes.", "content": "The alterations of three erythrocyte purine enzymes were studied in 12 patients with diseases associated with reticulocytosis, two patients with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, seven patients with severe megaloblastic anemia, and 14 normal subjects. The specific activity of adenine phosphoribosyltransferase was positively correlated (r = 0.81) with the reticulocyte percentate in ten patients with a normal hypoxanthine-guanine phosphoribosyltransferase. Two apparent types of alterations of this enzyme were distinguished: (1) increased specific activity with a normal half life as in megaloblastic anemia, and (2) a prolonged half life with or without an elevation of specific activity as in the deficiency of hypoxanthine-guanine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase were increased in megaloblastic anemia, but were not correlated with the reticulocyte percentage and did not have a consistent change in the half life in the other disorders studied. The data show that acquired disorders associated with reticulocytosis may cause an elevation of the specific activity of purine enzymes in peripheral circulating erythrocytes. Therefore, these factors must be carefully considered in the interpretation of an elevated level of enzyme activity.", "contents": "Acquired increases of human erythrocyte purine enzymes. The alterations of three erythrocyte purine enzymes were studied in 12 patients with diseases associated with reticulocytosis, two patients with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, seven patients with severe megaloblastic anemia, and 14 normal subjects. The specific activity of adenine phosphoribosyltransferase was positively correlated (r = 0.81) with the reticulocyte percentate in ten patients with a normal hypoxanthine-guanine phosphoribosyltransferase. Two apparent types of alterations of this enzyme were distinguished: (1) increased specific activity with a normal half life as in megaloblastic anemia, and (2) a prolonged half life with or without an elevation of specific activity as in the deficiency of hypoxanthine-guanine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase were increased in megaloblastic anemia, but were not correlated with the reticulocyte percentage and did not have a consistent change in the half life in the other disorders studied. The data show that acquired disorders associated with reticulocytosis may cause an elevation of the specific activity of purine enzymes in peripheral circulating erythrocytes. Therefore, these factors must be carefully considered in the interpretation of an elevated level of enzyme activity."} {"id": "PMID:177843", "title": "The stimulus-secretion coupling of glucose-induced insulin release. XX. fasting: a model for altered glucose recognition by the B-cell.", "content": "The rate of glucose uptake and oxidation, the output of lactate, the net uptake of calcium, the release of preformed or newly synthesized insulin and, possibly to a lesser extent, the biosynthesis of proinsulin are all diminished in islets removed from fasted rats and exposed to glucose. Theophylline and dibutyryl-adenosine-3',5'-cyclic monophosphate fail to fully restore a normal secretory response to glucose, despite the fact that they increase lactate production by the islets from fasted animals. The insulinotropic action of other secretagogues, including glyceraldehyde, leucine, beta-hydroxybutyrate, and sulfonylurea is unaffected by prior fasting of the donor rats. The islets metabolism of glyceraldehyde is also unaffected by fasting. These data indicate that fasting is associated with a block in glucose metabolism in the early steps of glycolysis, prior to the triose-phosphate level, and suggest that the insulin secretory response to glucose may be closely dependent on the rate at which the hexose is metabolized by islet tissue.", "contents": "The stimulus-secretion coupling of glucose-induced insulin release. XX. fasting: a model for altered glucose recognition by the B-cell. The rate of glucose uptake and oxidation, the output of lactate, the net uptake of calcium, the release of preformed or newly synthesized insulin and, possibly to a lesser extent, the biosynthesis of proinsulin are all diminished in islets removed from fasted rats and exposed to glucose. Theophylline and dibutyryl-adenosine-3',5'-cyclic monophosphate fail to fully restore a normal secretory response to glucose, despite the fact that they increase lactate production by the islets from fasted animals. The insulinotropic action of other secretagogues, including glyceraldehyde, leucine, beta-hydroxybutyrate, and sulfonylurea is unaffected by prior fasting of the donor rats. The islets metabolism of glyceraldehyde is also unaffected by fasting. These data indicate that fasting is associated with a block in glucose metabolism in the early steps of glycolysis, prior to the triose-phosphate level, and suggest that the insulin secretory response to glucose may be closely dependent on the rate at which the hexose is metabolized by islet tissue."} {"id": "PMID:177847", "title": "Fanconi's familial hypoplastic anaemia with some unusual features.", "content": "A case of Fanconi's familial hypoplastic anaemia is described in a 48-year-old woman who had the usual haematological and constitutional abnormalities of this condition. Chromosomal studies on peripheral blood lymphocytes and direct marrow preparations demonstrated the chromosomal breaks previously described. The age of the patient and a congenital abnormality of breast development were unusual features, while the discovery of a benign liver tumour at necropsy is of interest, as the patient had received therapy with oxymetholone.", "contents": "Fanconi's familial hypoplastic anaemia with some unusual features. A case of Fanconi's familial hypoplastic anaemia is described in a 48-year-old woman who had the usual haematological and constitutional abnormalities of this condition. Chromosomal studies on peripheral blood lymphocytes and direct marrow preparations demonstrated the chromosomal breaks previously described. The age of the patient and a congenital abnormality of breast development were unusual features, while the discovery of a benign liver tumour at necropsy is of interest, as the patient had received therapy with oxymetholone."} {"id": "PMID:177849", "title": "[Hospital-acquired hepatitis type B. Report of 6 cases (author's transl)].", "content": "Seroconversion was observed in 6 patients, indicating an infection with hepatitis virus B. All of these patients had been hospitalized with HBAg-positive persons a few weeks before, 5 of them because of acute hepatitis type A. While seroconversion was followed by acute hepatitis in 4 cases, the infection remained clinically silent in the other two patients. The second periods of illness were no attacks of relapsing hepatitis type A, as was indicated by HBAg. Vice versa superinfection of hepatitis B-patients with hepatitis virus A may occur, as is discussed in another case. Acute hepatitis is often transmitted in hospitals. Infective routes are discussed and means are described, by which is attempted, to reduce the incidence of hospital-acquired hepatitis.", "contents": "[Hospital-acquired hepatitis type B. Report of 6 cases (author's transl)]. Seroconversion was observed in 6 patients, indicating an infection with hepatitis virus B. All of these patients had been hospitalized with HBAg-positive persons a few weeks before, 5 of them because of acute hepatitis type A. While seroconversion was followed by acute hepatitis in 4 cases, the infection remained clinically silent in the other two patients. The second periods of illness were no attacks of relapsing hepatitis type A, as was indicated by HBAg. Vice versa superinfection of hepatitis B-patients with hepatitis virus A may occur, as is discussed in another case. Acute hepatitis is often transmitted in hospitals. Infective routes are discussed and means are described, by which is attempted, to reduce the incidence of hospital-acquired hepatitis."} {"id": "PMID:177846", "title": "Chronic cadmium poisoning.", "content": "Chronic cadmium poisoning occurs after prolonged exposure to the dust or fumes of cadmium-containing compounds. This paper describes the case of a pigment worker exposed to cadmium carbonate dust who exhibited many of the characteristic features of chronic cadmium poisoning.", "contents": "Chronic cadmium poisoning. Chronic cadmium poisoning occurs after prolonged exposure to the dust or fumes of cadmium-containing compounds. This paper describes the case of a pigment worker exposed to cadmium carbonate dust who exhibited many of the characteristic features of chronic cadmium poisoning."} {"id": "PMID:177854", "title": "Genetic and enzymatic analysis of a glycerol kinase deficient mutant in Neurospora crassa.", "content": "Genetic analysis showed that the glycerol non-utilizing isolate gly-u(234) of Neurospora crassa is derived by mutation in a nuclear gene situated in the right arm of linkage group I, about 2.2 cross-over units distal to ad-9 and 11 units proximal to nit-1. Enzymatic testings using a radiochemical method indicate that the mutant is deficient for the enzyme glycerol kinase. The radiochemical testings further indicate that the mutation has inactivated an inducible glycerol kinase, while a low residual activity may be due to a second, basal and non-inducible glycerol kinase, in accordance with a proposal by North (1973, 1974) that Neurospora has two glycerol kinases with these properties.", "contents": "Genetic and enzymatic analysis of a glycerol kinase deficient mutant in Neurospora crassa. Genetic analysis showed that the glycerol non-utilizing isolate gly-u(234) of Neurospora crassa is derived by mutation in a nuclear gene situated in the right arm of linkage group I, about 2.2 cross-over units distal to ad-9 and 11 units proximal to nit-1. Enzymatic testings using a radiochemical method indicate that the mutant is deficient for the enzyme glycerol kinase. The radiochemical testings further indicate that the mutation has inactivated an inducible glycerol kinase, while a low residual activity may be due to a second, basal and non-inducible glycerol kinase, in accordance with a proposal by North (1973, 1974) that Neurospora has two glycerol kinases with these properties."} {"id": "PMID:177856", "title": "Protein-liposome interactions and their relevance to the structure and function of cell membranes.", "content": "Recent studies on the interactions of soluble proteins, membrane proteins and enzymes with phospholipid model membranes are reviewed. Similarities between the properties of such systems and the behavior of biomembranes, such as alterations in the redox potential of cytochrome c after binding to membranes and effects of phospholipid fluidity on (Na+K) ATPase activity, are emphasized. The degree of correspondence between the behavior of model systems and natural membranes encourages the continuing use of model membranes in studies on protein-lipid interactions. However, some of the data on the increase of surface pressure of phospholipid monolayers by proteins and increases in the permeability of liposomes indicate that many soluble proteins also have a capability to interact hydrophobically with phospholipids. Thus a sharp distinction between both peripheral and integral membrane proteins and non-membrane proteins are not seen by these techniques. Cautious use of such studies, however, should lead to greater understanding of the molecular basis of cell membrane structure and function in normal and pathological states. Studies implicating protein-lipid interactions and (Na+K) ATPase activity in membrane alterations in disease states are also briefly discussed.", "contents": "Protein-liposome interactions and their relevance to the structure and function of cell membranes. Recent studies on the interactions of soluble proteins, membrane proteins and enzymes with phospholipid model membranes are reviewed. Similarities between the properties of such systems and the behavior of biomembranes, such as alterations in the redox potential of cytochrome c after binding to membranes and effects of phospholipid fluidity on (Na+K) ATPase activity, are emphasized. The degree of correspondence between the behavior of model systems and natural membranes encourages the continuing use of model membranes in studies on protein-lipid interactions. However, some of the data on the increase of surface pressure of phospholipid monolayers by proteins and increases in the permeability of liposomes indicate that many soluble proteins also have a capability to interact hydrophobically with phospholipids. Thus a sharp distinction between both peripheral and integral membrane proteins and non-membrane proteins are not seen by these techniques. Cautious use of such studies, however, should lead to greater understanding of the molecular basis of cell membrane structure and function in normal and pathological states. Studies implicating protein-lipid interactions and (Na+K) ATPase activity in membrane alterations in disease states are also briefly discussed."} {"id": "PMID:177859", "title": "On the histoenzymology of the human stomach.", "content": "By means of histochemical methods, the stomach in the man was studied for some oxidoreducing enzymes and hydrolases. The surface epithelium displays in the fundic area a mean activity which grows intense in the pyloric area. The parietal cells show a very high mitochondrial dehydrogenase activity, while the chief ones display a moderate oxidative activity. The pyloric glands exhibit a positive reaction for oxidoreducing enzymes with great differences of intensity from one cell to another. Around each principal and pyloric gland one can see an intense ATP-ase reaction in the endothelium of vessels and a very intense acid phosphate activity in the histiocytes. The submucosa, muscularis externa and serosa are very active for oxidoreduction and ATP-ase.", "contents": "On the histoenzymology of the human stomach. By means of histochemical methods, the stomach in the man was studied for some oxidoreducing enzymes and hydrolases. The surface epithelium displays in the fundic area a mean activity which grows intense in the pyloric area. The parietal cells show a very high mitochondrial dehydrogenase activity, while the chief ones display a moderate oxidative activity. The pyloric glands exhibit a positive reaction for oxidoreducing enzymes with great differences of intensity from one cell to another. Around each principal and pyloric gland one can see an intense ATP-ase reaction in the endothelium of vessels and a very intense acid phosphate activity in the histiocytes. The submucosa, muscularis externa and serosa are very active for oxidoreduction and ATP-ase."} {"id": "PMID:177860", "title": "Pleomorphous macrocellular pulmonary carcinomas. An anatomoclinical study on 193 cases.", "content": "A pathomorphologic study was carried out by the conventional histologic methods in 193 cases of pleomorphous macrocellular pulmonary carcinoma, of a total of 1,637 cases of lung cancer diagnosed histologically between January 1, 1961 and December 31, 1974. In comparison to other histologic types, the incidence of macrocellular carcinomas was of 11.8%, 62.6% belonged to the 40-60 years age-group, with male predominance. The results showed this carcinoma to be an autonomous type of neoplastic proliferation. The pathomorphologic particularities observed in the 193 cases and their evolution are conclusive arguments for considering pleomorphous macrocellular carcinomas as a separate histologic type in the classification of lung cancers. The term of pleomorphous macrocellular carcinoma appears to be the most comprehensive and in keeping with the histologic structure of these tumours. Cellular pleomorphism is an important diagnostic feature. Zones of specific differentiation observed in some cases may be included in the pleomorphism of these carcinomas. Notions of histogenesis are likewise discussed. It is increasingly assumed that these carcinomas are morphologically the expression of a cellular proliferation, differentiation and maturization response to the action of complex factors. The reduced stroma of these carcinomas indicate a more rapid increase of the tumoural parenchyma.", "contents": "Pleomorphous macrocellular pulmonary carcinomas. An anatomoclinical study on 193 cases. A pathomorphologic study was carried out by the conventional histologic methods in 193 cases of pleomorphous macrocellular pulmonary carcinoma, of a total of 1,637 cases of lung cancer diagnosed histologically between January 1, 1961 and December 31, 1974. In comparison to other histologic types, the incidence of macrocellular carcinomas was of 11.8%, 62.6% belonged to the 40-60 years age-group, with male predominance. The results showed this carcinoma to be an autonomous type of neoplastic proliferation. The pathomorphologic particularities observed in the 193 cases and their evolution are conclusive arguments for considering pleomorphous macrocellular carcinomas as a separate histologic type in the classification of lung cancers. The term of pleomorphous macrocellular carcinoma appears to be the most comprehensive and in keeping with the histologic structure of these tumours. Cellular pleomorphism is an important diagnostic feature. Zones of specific differentiation observed in some cases may be included in the pleomorphism of these carcinomas. Notions of histogenesis are likewise discussed. It is increasingly assumed that these carcinomas are morphologically the expression of a cellular proliferation, differentiation and maturization response to the action of complex factors. The reduced stroma of these carcinomas indicate a more rapid increase of the tumoural parenchyma."} {"id": "PMID:177861", "title": "[Bacterial resistance factors as vectors for gene manipulation and gene therapy (author's transl)].", "content": "Bacterial resistance factors are extrachromosomal elements, consisting of circular closed, double stranded DNA. They may contain genes which make the host bacterium resistant to certain antibiotics. Such resistance factors have become important vectors for selective replication of specific segments of all kinds of DNA. Suitable DNA segments are obtained by treating DNA with restriction endonucleases of defined cutting properties. They can then be linked to the respective vector. It was thus possible to anneal DNA segments originating from the same, but also from different bacterial resistance factors. They gave biologically functional units. The annealed products can be propagated in bacteria. The relevant experiments are described. Their potential dangers for man, and efforts to agree on suitable safety regulations are discussed.", "contents": "[Bacterial resistance factors as vectors for gene manipulation and gene therapy (author's transl)]. Bacterial resistance factors are extrachromosomal elements, consisting of circular closed, double stranded DNA. They may contain genes which make the host bacterium resistant to certain antibiotics. Such resistance factors have become important vectors for selective replication of specific segments of all kinds of DNA. Suitable DNA segments are obtained by treating DNA with restriction endonucleases of defined cutting properties. They can then be linked to the respective vector. It was thus possible to anneal DNA segments originating from the same, but also from different bacterial resistance factors. They gave biologically functional units. The annealed products can be propagated in bacteria. The relevant experiments are described. Their potential dangers for man, and efforts to agree on suitable safety regulations are discussed."} {"id": "PMID:177862", "title": "[Conception of programmed and standardized after-care of mammary carcinoma (author's transl)].", "content": "Optimal after-care of mammary carcinoma begins with the end of the primary therapy and lasts practically for a lifetime. The after-care consists of several inpatient follow-ups in specially equipped follow-up clinics, of outpatient after-care by the general practitioner and of care by appointment at the treatment center. Standardized diagnostic methods combined with programmed appointments form the basis of an effective after-care for mammary carcinoma. The essence of a programmed and standardized after-care for mammary carcinoma lies in the fact that all participants are forced into a uniform and scheduled procedure by which the observance of a minimum program is guaranteed.", "contents": "[Conception of programmed and standardized after-care of mammary carcinoma (author's transl)]. Optimal after-care of mammary carcinoma begins with the end of the primary therapy and lasts practically for a lifetime. The after-care consists of several inpatient follow-ups in specially equipped follow-up clinics, of outpatient after-care by the general practitioner and of care by appointment at the treatment center. Standardized diagnostic methods combined with programmed appointments form the basis of an effective after-care for mammary carcinoma. The essence of a programmed and standardized after-care for mammary carcinoma lies in the fact that all participants are forced into a uniform and scheduled procedure by which the observance of a minimum program is guaranteed."} {"id": "PMID:177863", "title": "[Effect of clofibrate on glucose tolerance and insulin secretion in patients with endogenous hypertriglyceridemia (author's transl)].", "content": "In 22 patients with endogenous hypertriglyceridemia, oral and intravenous glucose tolerance showed significant improvement under clofibrate treatment which was in no way correlated to the fall in triglycerides. Basal and stimulated insulin, cholesterol and fasting blood sugar did not change, body weight remained constant and was not correlated to the degree of hypertriglyceridemia. On the other hand a positive correlation between body weight and insulin concentrations was found. Improvement of glucose tolerance independently of body weight and insulin may be due to a direct effect of clofibrate on glucose metabolism without any correlation to its triglyceride-lowering.", "contents": "[Effect of clofibrate on glucose tolerance and insulin secretion in patients with endogenous hypertriglyceridemia (author's transl)]. In 22 patients with endogenous hypertriglyceridemia, oral and intravenous glucose tolerance showed significant improvement under clofibrate treatment which was in no way correlated to the fall in triglycerides. Basal and stimulated insulin, cholesterol and fasting blood sugar did not change, body weight remained constant and was not correlated to the degree of hypertriglyceridemia. On the other hand a positive correlation between body weight and insulin concentrations was found. Improvement of glucose tolerance independently of body weight and insulin may be due to a direct effect of clofibrate on glucose metabolism without any correlation to its triglyceride-lowering."} {"id": "PMID:177864", "title": "The mutability of the minute loci of Drosophila melanogaster with ethyl methanesulfonate.", "content": "It has been suggested that the Minute loci of Drosophila melanogaster are the redundant structural loci for the transfer RNA's [31]. To inquire whether the Minute loci differed from other loci in their genetic organization we have determined the dose response curves for the induction of Minutes and sex-linked recessive lethals with ethyl methanesulfonate (EMS). There are approx. 67.75 +/- 9.35 Minute mutants induced for every 5000 recessive lethals induced in the genome and this relationship is independent of EMS dosage. This is in good agreement with the relative numbers of Minute and lethal loci in the genome. Because the target size of the average Minute locus is the same as that of the average locus capable of mutating to a lethal, these data do not support the view that the Minute loci are special in their genetic organization. Since Minute mutants can be scored in the F1 of mutagenized flies it is suggested that the induction of Minute mutants may provide a more rapid and economical means of assessing mutagenicity than do traditional screens for the induction of recessive lethals.", "contents": "The mutability of the minute loci of Drosophila melanogaster with ethyl methanesulfonate. It has been suggested that the Minute loci of Drosophila melanogaster are the redundant structural loci for the transfer RNA's [31]. To inquire whether the Minute loci differed from other loci in their genetic organization we have determined the dose response curves for the induction of Minutes and sex-linked recessive lethals with ethyl methanesulfonate (EMS). There are approx. 67.75 +/- 9.35 Minute mutants induced for every 5000 recessive lethals induced in the genome and this relationship is independent of EMS dosage. This is in good agreement with the relative numbers of Minute and lethal loci in the genome. Because the target size of the average Minute locus is the same as that of the average locus capable of mutating to a lethal, these data do not support the view that the Minute loci are special in their genetic organization. Since Minute mutants can be scored in the F1 of mutagenized flies it is suggested that the induction of Minute mutants may provide a more rapid and economical means of assessing mutagenicity than do traditional screens for the induction of recessive lethals."} {"id": "PMID:177865", "title": "Mutagenesis studies on cultured mammalian cells. The sensitivity of the asparagine-requiring phenotype to several chemical agents.", "content": "The effect of several chemical agents on the mutation frequency from asparagine dependence to asparagine independence has been studied in Jensen sarcoma cells. It was found that ethylmethanesulfonate brought about a dramatic exponential increase, while nitrosoguanidine was not lighly effective as a mutagen, causing only a modest increase in mutation frequency, and quinacrine HCl was ineffective. The results presented here are compared with those obtained in other systems and with our previous work on the effects of UV on mutation induction in the asparagine system. They suggest that the basis of the asparagine requirement of mammalian cell lines resides in a specific genetic alteration in nuclear DNA which is corrected by the mutagenic action of the agents tested here.", "contents": "Mutagenesis studies on cultured mammalian cells. The sensitivity of the asparagine-requiring phenotype to several chemical agents. The effect of several chemical agents on the mutation frequency from asparagine dependence to asparagine independence has been studied in Jensen sarcoma cells. It was found that ethylmethanesulfonate brought about a dramatic exponential increase, while nitrosoguanidine was not lighly effective as a mutagen, causing only a modest increase in mutation frequency, and quinacrine HCl was ineffective. The results presented here are compared with those obtained in other systems and with our previous work on the effects of UV on mutation induction in the asparagine system. They suggest that the basis of the asparagine requirement of mammalian cell lines resides in a specific genetic alteration in nuclear DNA which is corrected by the mutagenic action of the agents tested here."} {"id": "PMID:177866", "title": "Adenine arabinoside therapy of herpes zoster in the immunosuppressed. NIAID collaborative antiviral study.", "content": "We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.001). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia (P = 0.001) and are less than 38 years of age (P = 0.001).", "contents": "Adenine arabinoside therapy of herpes zoster in the immunosuppressed. NIAID collaborative antiviral study. We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.001). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia (P = 0.001) and are less than 38 years of age (P = 0.001)."} {"id": "PMID:177869", "title": "Myocardial infarction and estrogen therapy in post-menopausal women.", "content": "Data obtained from two multipurpose surveys of hospitalized patients were examined to determine the risk of nonfatal acute myocardial infarction in post-menopausal women 40 to 75 years of age in relation to use of estrogen-containing drugs. Eight (2.4 per cent) of 336 myocardial infarction patients and 330 (4.9 per cent) of 6730 reference patients were regular estrogen users (crude rate ratio, 0.47) at the time of hospitalization. After control for confounding variables -- among them, age, past history of myocardial in farction, angina, diabetes, and hypertension (alone or in combination) and cigarette smoking -- the summary point estimate of rate ratio was 0.97 with 95 per cent confidence limits of 0.48 and 1.95. Thus, there was no evidence of a statistically significant association between current regular use of estrogens and nonfatal acute myocardial infarction.", "contents": "Myocardial infarction and estrogen therapy in post-menopausal women. Data obtained from two multipurpose surveys of hospitalized patients were examined to determine the risk of nonfatal acute myocardial infarction in post-menopausal women 40 to 75 years of age in relation to use of estrogen-containing drugs. Eight (2.4 per cent) of 336 myocardial infarction patients and 330 (4.9 per cent) of 6730 reference patients were regular estrogen users (crude rate ratio, 0.47) at the time of hospitalization. After control for confounding variables -- among them, age, past history of myocardial in farction, angina, diabetes, and hypertension (alone or in combination) and cigarette smoking -- the summary point estimate of rate ratio was 0.97 with 95 per cent confidence limits of 0.48 and 1.95. Thus, there was no evidence of a statistically significant association between current regular use of estrogens and nonfatal acute myocardial infarction."} {"id": "PMID:177870", "title": "Estrogens and endometrial cancer in a retirement community.", "content": "All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer.", "contents": "Estrogens and endometrial cancer in a retirement community. All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer."} {"id": "PMID:177872", "title": "Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx.", "content": "In an examination of excretion patterns of Epstein-Barr virus in 104 throat washings from 20 patients with infectious mononucleosis we found that three persons regularly shed virus from the second week through the third month after onset; 15 demonstrated intermittent excretion over three months, and in two cases, no virus was detected. In oral secretions, the virus appeared to be located extracellularly. Transforming activity was demonstrated in aliquots after centrifugation and filtration, in a sample in which cells were disrupted before filtration, and in specimens after two years' storage. Multiple oropharyngeal sites were examined for presence of the virus. In one patient, virus was regularly demonstrated in throat washings and saliva; swabs from Stensen's duct orifices yielded virus in three of four cases. Demonstration of virus in these oropharyngeal specimens explains increased transmissibility in age groups in which salivary exchange is high.", "contents": "Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx. In an examination of excretion patterns of Epstein-Barr virus in 104 throat washings from 20 patients with infectious mononucleosis we found that three persons regularly shed virus from the second week through the third month after onset; 15 demonstrated intermittent excretion over three months, and in two cases, no virus was detected. In oral secretions, the virus appeared to be located extracellularly. Transforming activity was demonstrated in aliquots after centrifugation and filtration, in a sample in which cells were disrupted before filtration, and in specimens after two years' storage. Multiple oropharyngeal sites were examined for presence of the virus. In one patient, virus was regularly demonstrated in throat washings and saliva; swabs from Stensen's duct orifices yielded virus in three of four cases. Demonstration of virus in these oropharyngeal specimens explains increased transmissibility in age groups in which salivary exchange is high."} {"id": "PMID:177873", "title": "Radiation and high-dose metronidazole in supratentorial glioblastomas.", "content": "We used \"high-dose\" metronidazole, an \"in vitro\" and \"in vivo\" specific radiosensitizer of hypoxic cells, in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas. Thirty-six patients were stratified according to functional level and randomly allocated within two weeks of operation to one of two therapeutic groups: Group 1, radiation alone; and Group 2, radiation as in Group 1 but with high-dose metronidazole. We examined survival with the Kaplan-Meier probability plot and non-parametric tests. Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death (P = 0.02). This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant. Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors.", "contents": "Radiation and high-dose metronidazole in supratentorial glioblastomas. We used \"high-dose\" metronidazole, an \"in vitro\" and \"in vivo\" specific radiosensitizer of hypoxic cells, in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas. Thirty-six patients were stratified according to functional level and randomly allocated within two weeks of operation to one of two therapeutic groups: Group 1, radiation alone; and Group 2, radiation as in Group 1 but with high-dose metronidazole. We examined survival with the Kaplan-Meier probability plot and non-parametric tests. Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death (P = 0.02). This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant. Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors."} {"id": "PMID:177891", "title": "Susceptibility of chickens to avian encephalomyelitis virus. II. Behavior of the virus in day-old chicks.", "content": "The VR strain of avian encephalomyelitis virus, which had been adapted to embryonated hen's eggs, was inoculated into 2-day-old chicks by the subcutaneous route (10(2.5) approximately 10(3.0) EID50) or by the oral route (10(4.8) EID50). The chicks were examined chronologically for the distribution of the virus in the body. As a result, minute amounts of the virus were detected from the liver, spleen, pancreas, and muscle at the site of inoculation one day after inoculation and various amounts from almost all the organs 3 days and more after inoculation. The virus titer could nearly reach a maximum 7 to 9 days after inoculation. Above all, such high virus titers as ranging from 10(4.3) to 10(5.8) EID50/0.1 g were demonstrated in the brain, heart, liver, spleen, and pancreas. After that, there was a tendency for virus titer to decrease in most organs and for virus to multiply persistently in the pancreas, brain, and eyeball. Virus titer was maintained at a level of 10(2.3) approximately 10(2.8) EID50/0.1 g in these three organs even 21 days after inoculation. In the group of subcutaneous inoculation, all the chicks manifested clinical signs of infection 5 to 10 days after inoculation. On the other hand, no chicks were involved in clinical infection in the group of oral inoculation. Multiplication of the virus was delayed in the body of these chicks. Small amounts of the virus were detected from the spleen and pancreas 11 days after inoculation. Low titers (10(2.7) EID50/0.1 g at the highest) of the virus were only detected from the brain, spinal cord, spleen, pancreas, esophagus, and other organs 14 and 21 days after inoculation.", "contents": "Susceptibility of chickens to avian encephalomyelitis virus. II. Behavior of the virus in day-old chicks. The VR strain of avian encephalomyelitis virus, which had been adapted to embryonated hen's eggs, was inoculated into 2-day-old chicks by the subcutaneous route (10(2.5) approximately 10(3.0) EID50) or by the oral route (10(4.8) EID50). The chicks were examined chronologically for the distribution of the virus in the body. As a result, minute amounts of the virus were detected from the liver, spleen, pancreas, and muscle at the site of inoculation one day after inoculation and various amounts from almost all the organs 3 days and more after inoculation. The virus titer could nearly reach a maximum 7 to 9 days after inoculation. Above all, such high virus titers as ranging from 10(4.3) to 10(5.8) EID50/0.1 g were demonstrated in the brain, heart, liver, spleen, and pancreas. After that, there was a tendency for virus titer to decrease in most organs and for virus to multiply persistently in the pancreas, brain, and eyeball. Virus titer was maintained at a level of 10(2.3) approximately 10(2.8) EID50/0.1 g in these three organs even 21 days after inoculation. In the group of subcutaneous inoculation, all the chicks manifested clinical signs of infection 5 to 10 days after inoculation. On the other hand, no chicks were involved in clinical infection in the group of oral inoculation. Multiplication of the virus was delayed in the body of these chicks. Small amounts of the virus were detected from the spleen and pancreas 11 days after inoculation. Low titers (10(2.7) EID50/0.1 g at the highest) of the virus were only detected from the brain, spinal cord, spleen, pancreas, esophagus, and other organs 14 and 21 days after inoculation."} {"id": "PMID:177892", "title": "Pathogenicity for chicks of line cells from lymphoma of Marek's disease.", "content": "Pathogenicity for chicks of the MSB-1 line, a cell line derived from the tumorous tissue of a chick with Marek's disease (MD) and established by Akiyama & Kato, was studied. Five groups, including a control one, of 20 chicks each were inoculated with 1 X 10(3), 1 X 10(4), 1 X 10(5), 1 X 10(6) and no cells of a 180-day culture of the cell line at one day of age. They were housed all together in an isolation unit. An attempt was first made successfully to isolate MD virus (MDV) directly in culture of kidney cells 3 weeks after inoculation. Horizontal infection was first detected 4 weeks after inoculation. From 3 weeks after inoculation on, the disease with almost the same clinical and pathological pictures as the infection with a virulent strain of MDV showed a high incidence. Morbidity was closely related to the number of MSB-1 line cells inoculated. Parenchymal destruction was conspicuous in the central lymphoid organs of four chicks given the largest number of MSB-1 line cells and sacrificed in extremis about 4 weeks after inoculation. Establishment of MD in chicks inoculated with MSB-1 line cells carrying MDV genome seemed to be initiated under the circumstances where the line cells which had come into contact with susceptible cells in the peritoneal cavity released virulent MDV per se. Then host chicks might be infected with MDV and suffer from MD at a high rate. There was no great difference in oncogenic potential between MSB-1 line cells cultivated in vitro for 180 days and virulent MDV serially passaged through one-day-old chicks.", "contents": "Pathogenicity for chicks of line cells from lymphoma of Marek's disease. Pathogenicity for chicks of the MSB-1 line, a cell line derived from the tumorous tissue of a chick with Marek's disease (MD) and established by Akiyama & Kato, was studied. Five groups, including a control one, of 20 chicks each were inoculated with 1 X 10(3), 1 X 10(4), 1 X 10(5), 1 X 10(6) and no cells of a 180-day culture of the cell line at one day of age. They were housed all together in an isolation unit. An attempt was first made successfully to isolate MD virus (MDV) directly in culture of kidney cells 3 weeks after inoculation. Horizontal infection was first detected 4 weeks after inoculation. From 3 weeks after inoculation on, the disease with almost the same clinical and pathological pictures as the infection with a virulent strain of MDV showed a high incidence. Morbidity was closely related to the number of MSB-1 line cells inoculated. Parenchymal destruction was conspicuous in the central lymphoid organs of four chicks given the largest number of MSB-1 line cells and sacrificed in extremis about 4 weeks after inoculation. Establishment of MD in chicks inoculated with MSB-1 line cells carrying MDV genome seemed to be initiated under the circumstances where the line cells which had come into contact with susceptible cells in the peritoneal cavity released virulent MDV per se. Then host chicks might be infected with MDV and suffer from MD at a high rate. There was no great difference in oncogenic potential between MSB-1 line cells cultivated in vitro for 180 days and virulent MDV serially passaged through one-day-old chicks."} {"id": "PMID:177894", "title": "Recrudescence of equine infectious anemia by treatment with immunosuppressive drugs.", "content": "Horses which had passed a few months to a few years asymptomatically after the last recurrence of equine infectious anemia (EIA) showed a typical febrile response after treatment with the immunosuppressive agent, dexamethasone (DM) or cyclophosphamide (CY). In horses showing a febrile response, EIA virus which had not been neutralized by neutralizing antibody previously produced was propagated. In DM-treated horses it disappeared from the blood soon after pyretolysis and antibody against the virus was produced promptly. In contrast, detectable viremia persisted in CY-treated horses for 10 to 84 days after pyretolysis. Antibody against the virus was barely produced for 42 to 126 days after treatment. After drug treatment, there was no decrease in neutralizing antibody previously produced. Then, it was inferred that this febrile response was due to propagation of an immunologically variant virus which might have been produced as a result of decline in cell-mediated immunity. The role of cellular mechanisms in the development of immunity to EIA was also discussed.", "contents": "Recrudescence of equine infectious anemia by treatment with immunosuppressive drugs. Horses which had passed a few months to a few years asymptomatically after the last recurrence of equine infectious anemia (EIA) showed a typical febrile response after treatment with the immunosuppressive agent, dexamethasone (DM) or cyclophosphamide (CY). In horses showing a febrile response, EIA virus which had not been neutralized by neutralizing antibody previously produced was propagated. In DM-treated horses it disappeared from the blood soon after pyretolysis and antibody against the virus was produced promptly. In contrast, detectable viremia persisted in CY-treated horses for 10 to 84 days after pyretolysis. Antibody against the virus was barely produced for 42 to 126 days after treatment. After drug treatment, there was no decrease in neutralizing antibody previously produced. Then, it was inferred that this febrile response was due to propagation of an immunologically variant virus which might have been produced as a result of decline in cell-mediated immunity. The role of cellular mechanisms in the development of immunity to EIA was also discussed."} {"id": "PMID:177895", "title": "[Transmission of impulse trains by nerve fibers upon near-threshold stimulation].", "content": "Impulse trains evoked by stimulation of the hindlimb nerves were studied in group A fibres at the lumbar level of spinal cord in anesthetized cats. Random (Poissonian) trains fo stimuli and trains with modified structure were used. With suprathreshold stimulation the impulse trains in the nerve fibres differed from the stimulus trains only by the absence of the shortest (less than 1.0 divided by 1.5 ms) intervals caused by refracteriness. Substantial differencies between the impulse and stimulus trains occurred when the stimulus intensity was decreased to a near-threshold level and mean frequency of stimulation was higher than 10 per second. Differences were found in interval histograms, intensity functions, correlation coefficients for successive intervals. Afterdischarge processes in the nerve fibres are supposed to be the main reason of changes in the impulse train structure.", "contents": "[Transmission of impulse trains by nerve fibers upon near-threshold stimulation]. Impulse trains evoked by stimulation of the hindlimb nerves were studied in group A fibres at the lumbar level of spinal cord in anesthetized cats. Random (Poissonian) trains fo stimuli and trains with modified structure were used. With suprathreshold stimulation the impulse trains in the nerve fibres differed from the stimulus trains only by the absence of the shortest (less than 1.0 divided by 1.5 ms) intervals caused by refracteriness. Substantial differencies between the impulse and stimulus trains occurred when the stimulus intensity was decreased to a near-threshold level and mean frequency of stimulation was higher than 10 per second. Differences were found in interval histograms, intensity functions, correlation coefficients for successive intervals. Afterdischarge processes in the nerve fibres are supposed to be the main reason of changes in the impulse train structure."} {"id": "PMID:177898", "title": "Growth potential and skeletal maturity in children with chronic renal insufficiency.", "content": "The growth potential of 27 boys with varying degrees of chronic renal insufficiency has been determined from their present height centile for both bone age and chronological age. With increasing age their growth potential diminishes. The delay in bone age is greatest in those children whose disease dates from infancy, but does not correlate with their present state of renal function. Bone age continues to advance in the presence of severe osteodystrophy and growth arrest. Knowledge of the growth potential of children with chronic renal failure is of relevance in interpreting the height increments observed following renal transplantation. Serial determination of bone age is therefore an important aspect of their clinical management.", "contents": "Growth potential and skeletal maturity in children with chronic renal insufficiency. The growth potential of 27 boys with varying degrees of chronic renal insufficiency has been determined from their present height centile for both bone age and chronological age. With increasing age their growth potential diminishes. The delay in bone age is greatest in those children whose disease dates from infancy, but does not correlate with their present state of renal function. Bone age continues to advance in the presence of severe osteodystrophy and growth arrest. Knowledge of the growth potential of children with chronic renal failure is of relevance in interpreting the height increments observed following renal transplantation. Serial determination of bone age is therefore an important aspect of their clinical management."} {"id": "PMID:177900", "title": "Effects of an intraventricular injection of synthetic ACTH on plasma testosterone, progesterone and LH levels and on sexual behavior in male and female rabbits.", "content": "Sexual behavior and elevation of gonadal steroids were induced in both male and female New Zealand white rabbits following injection of synthetic beta (1-24) ACTH into the lateral cerebral ventricle. In blood assays collected by cardiac puncture, testosterone, progesterone and corticosterone were all increased above both resting levels and samples were taken after a control intraventricular injection of physiological saline. Parallel increases of plasma LH were also demonstrated. The results were interpreted to indicate that intraventricular ACTH, through LH release, influences sex hormone levels and sexual behavior by 'centrally', probably within the hypothalamus.", "contents": "Effects of an intraventricular injection of synthetic ACTH on plasma testosterone, progesterone and LH levels and on sexual behavior in male and female rabbits. Sexual behavior and elevation of gonadal steroids were induced in both male and female New Zealand white rabbits following injection of synthetic beta (1-24) ACTH into the lateral cerebral ventricle. In blood assays collected by cardiac puncture, testosterone, progesterone and corticosterone were all increased above both resting levels and samples were taken after a control intraventricular injection of physiological saline. Parallel increases of plasma LH were also demonstrated. The results were interpreted to indicate that intraventricular ACTH, through LH release, influences sex hormone levels and sexual behavior by 'centrally', probably within the hypothalamus."} {"id": "PMID:177902", "title": "Rapid eye movement sleep alterations in myasthenia gravis.", "content": "The nocturnal sleep patterns of 10 patients with myasthenia gravis and five controls were recorded in the conventional manner for 7 hours on two consecutive nights. One patient was retested 4 weeks after institution of prednisone therapy. All the myasthenics had a significant disturbance in rapid eye movement (REM) sleep cycles. In the patient who was retested after clinically successful prednisone therapy, the REM sleep pattern had become normal. Since acetylcholine is the putative brain stem transmitter substance involved in the maintenance of REM sleep, our findings suggest a disturbed central mechanism of acetylcholine in myasthenia gravis.", "contents": "Rapid eye movement sleep alterations in myasthenia gravis. The nocturnal sleep patterns of 10 patients with myasthenia gravis and five controls were recorded in the conventional manner for 7 hours on two consecutive nights. One patient was retested 4 weeks after institution of prednisone therapy. All the myasthenics had a significant disturbance in rapid eye movement (REM) sleep cycles. In the patient who was retested after clinically successful prednisone therapy, the REM sleep pattern had become normal. Since acetylcholine is the putative brain stem transmitter substance involved in the maintenance of REM sleep, our findings suggest a disturbed central mechanism of acetylcholine in myasthenia gravis."} {"id": "PMID:177903", "title": "Electrophysiologic diagnosis of myasthenia gravis and the regional curare test.", "content": "Two hundred and fifty consecutive patients were evaluated for myasthenia gravis with repetitive supramaximal stimulation of peripheral nerves and regional curare administration when necessary. Among patients with definite generalized myasthenia gravis, 72 percent had abnormal responses to repetitive supramaximal stimulation alone and another 17 percent had abnormal responses after regional curare administration. Among those with possible generalized myasthenia gravis, 15 percent had abnormal responses to repetitive supramaximal stimulation and another 12 percent had abnormal responses after regional curare administration. Of those with only ocular symptoms, 46 percent had abnormal responses to repetitive supramaximal stimulation before or after regional curare administration, suggesting generalized involvement. Myasthenia gravis has not developed subsequently in any of the equivocal patients with negative electric tests. We have found these electric procedures to be simple, safe, and at least as effective as other methods in diagnosing myasthenia gravis.", "contents": "Electrophysiologic diagnosis of myasthenia gravis and the regional curare test. Two hundred and fifty consecutive patients were evaluated for myasthenia gravis with repetitive supramaximal stimulation of peripheral nerves and regional curare administration when necessary. Among patients with definite generalized myasthenia gravis, 72 percent had abnormal responses to repetitive supramaximal stimulation alone and another 17 percent had abnormal responses after regional curare administration. Among those with possible generalized myasthenia gravis, 15 percent had abnormal responses to repetitive supramaximal stimulation and another 12 percent had abnormal responses after regional curare administration. Of those with only ocular symptoms, 46 percent had abnormal responses to repetitive supramaximal stimulation before or after regional curare administration, suggesting generalized involvement. Myasthenia gravis has not developed subsequently in any of the equivocal patients with negative electric tests. We have found these electric procedures to be simple, safe, and at least as effective as other methods in diagnosing myasthenia gravis."} {"id": "PMID:177899", "title": "[Importance of early hormonal treatment of salaam seizures for the further course of epilepsy in children].", "content": "The authors analysed 13 cases of West's syndrome (8 females and 5 males observed in a period of 30 months. In only one case there was history of perinatal trauma. In 7 children the psychomotor development was very good until the time of development of seizures, in 2 children hyperexcitability was present, 1 was obese, 2 had various infections. In 7 cases the seizures developed within 1 to 20 days after DiPerTe or poliomyelitis vaccination. The time from the onset of seizures to beginning of hormonal treatment ranged from 4 weeks to 5 months. Corticosteroids or ACTH were administered for 2 months at least, and benzodiazepine drugs and/or phenobarbital were given additionally. It was found that the effects of treatment were much better in children referred for treatment early after onset of seizures. In cases with delayed hormonal treatment mental retardation was considerable and seizures were frequent.", "contents": "[Importance of early hormonal treatment of salaam seizures for the further course of epilepsy in children]. The authors analysed 13 cases of West's syndrome (8 females and 5 males observed in a period of 30 months. In only one case there was history of perinatal trauma. In 7 children the psychomotor development was very good until the time of development of seizures, in 2 children hyperexcitability was present, 1 was obese, 2 had various infections. In 7 cases the seizures developed within 1 to 20 days after DiPerTe or poliomyelitis vaccination. The time from the onset of seizures to beginning of hormonal treatment ranged from 4 weeks to 5 months. Corticosteroids or ACTH were administered for 2 months at least, and benzodiazepine drugs and/or phenobarbital were given additionally. It was found that the effects of treatment were much better in children referred for treatment early after onset of seizures. In cases with delayed hormonal treatment mental retardation was considerable and seizures were frequent."} {"id": "PMID:177904", "title": "Pain in peripheral neuropathy related to rate and kind of fiber degeneration.", "content": "In a series of 72 patients with disease of peripheral neurons, neuropathic painfulness of the foot was found to be related to the rate and kind of nerve fiber degeneration. Patients with acute breakdown of myelinated fibers (either by wallerian or axonal degeneration) tend to have pain more often and to a greater degree than do patients with more chronic forms of nerve fiber degeneration. Neuropathic painfulness was not found to be related simply to the ratio of remaining large and small fibers after nerve fiber degeneration. These studies do not fit the expectation of the proponents of the gate theory of pain.", "contents": "Pain in peripheral neuropathy related to rate and kind of fiber degeneration. In a series of 72 patients with disease of peripheral neurons, neuropathic painfulness of the foot was found to be related to the rate and kind of nerve fiber degeneration. Patients with acute breakdown of myelinated fibers (either by wallerian or axonal degeneration) tend to have pain more often and to a greater degree than do patients with more chronic forms of nerve fiber degeneration. Neuropathic painfulness was not found to be related simply to the ratio of remaining large and small fibers after nerve fiber degeneration. These studies do not fit the expectation of the proponents of the gate theory of pain."} {"id": "PMID:177905", "title": "The acetylcholine receptor in normal and pathologic states. Immunoperoxidase visualization of alpha-bungarotoxin binding at a light and electron-microscopic level.", "content": "Acetylcholine receptor now can be visualized in the muscle sarcolemmal membrane with the use of an immunoperoxidase staining of alpha-bungarotoxin (alpha BT), a substance that binds specifically to the acetylcholine receptor. This technique has allowed new observations in various neuromuscular diseases in which the acetylcholine receptor is affected. In normal muscle, the acetylcholine receptor is confined to the neuromuscular junction. In both experimental denervation and human denervating illnesses, the acetylcholine receptor becomes present diffusely along the muscle sarcolemmal membrane in denervated fibers. In myasthenia gravis, a circulating factor that blocks alpha BT binding to the acetylcholine receptor of either normal neuromuscular junctions or denervated sarcolemmal membranes is present in 68 percent of serums tested.", "contents": "The acetylcholine receptor in normal and pathologic states. Immunoperoxidase visualization of alpha-bungarotoxin binding at a light and electron-microscopic level. Acetylcholine receptor now can be visualized in the muscle sarcolemmal membrane with the use of an immunoperoxidase staining of alpha-bungarotoxin (alpha BT), a substance that binds specifically to the acetylcholine receptor. This technique has allowed new observations in various neuromuscular diseases in which the acetylcholine receptor is affected. In normal muscle, the acetylcholine receptor is confined to the neuromuscular junction. In both experimental denervation and human denervating illnesses, the acetylcholine receptor becomes present diffusely along the muscle sarcolemmal membrane in denervated fibers. In myasthenia gravis, a circulating factor that blocks alpha BT binding to the acetylcholine receptor of either normal neuromuscular junctions or denervated sarcolemmal membranes is present in 68 percent of serums tested."} {"id": "PMID:177911", "title": "Koilocytotic atypia of the cervix.", "content": "Koilocytotic atypia was found in 217 of 858 cervical biopsies obtained during a 26-month period. Koilocytotic change was more common in younger women. Nuclear atypia in the koilocytotic cells was associated with cervical dysplasia in a high proportion of cases. There was a significant difference in the incidence of dysplasia in koilocytosis with marked nuclear atypia when compared to koilocytosis without nuclear atypia. In some cases koilocytosis was associated with vesicular changes in the cervical epithelium. The significance of this change and its association with other abnormalities of the cervix is discussed.", "contents": "Koilocytotic atypia of the cervix. Koilocytotic atypia was found in 217 of 858 cervical biopsies obtained during a 26-month period. Koilocytotic change was more common in younger women. Nuclear atypia in the koilocytotic cells was associated with cervical dysplasia in a high proportion of cases. There was a significant difference in the incidence of dysplasia in koilocytosis with marked nuclear atypia when compared to koilocytosis without nuclear atypia. In some cases koilocytosis was associated with vesicular changes in the cervical epithelium. The significance of this change and its association with other abnormalities of the cervix is discussed."} {"id": "PMID:177912", "title": "Cytomegalic virus disease in pregnancy.", "content": "A case report is presented in which cytomegalic virus inclusion bodies were demonstrated in twin placentas and in both infants. This is the fourth such report in the English language literature. The case also demonstrated interlocking of the fetal heads requiring decapitation of the dead twin in order to deliver the surviving twin. The survivor showed gross stigmas of cytomegalic viral disease.", "contents": "Cytomegalic virus disease in pregnancy. A case report is presented in which cytomegalic virus inclusion bodies were demonstrated in twin placentas and in both infants. This is the fourth such report in the English language literature. The case also demonstrated interlocking of the fetal heads requiring decapitation of the dead twin in order to deliver the surviving twin. The survivor showed gross stigmas of cytomegalic viral disease."} {"id": "PMID:177922", "title": "Adenoid cystic carcinoma. Analysis of fifty oral cases.", "content": "Fifty cases of oral minor salivary gland adenoid cystic carcinoma (ACC) are analyzed and reported. Oral ACC frequently masquerades as a benign neoplasm, and in the majority of cases there is no pain or ulceration. The most common location is in the palate; a plea is made for incisional biopsy of all oral lesions suspected of salivary gland origin. Survival rates show a progressive decrease with time, and there were no survivors beyond 20 years. In this study, there was a positive correlation between duration of the lesion before diagnosis and the salvage rate, but no correlation was found with the size of the presenting lesion.", "contents": "Adenoid cystic carcinoma. Analysis of fifty oral cases. Fifty cases of oral minor salivary gland adenoid cystic carcinoma (ACC) are analyzed and reported. Oral ACC frequently masquerades as a benign neoplasm, and in the majority of cases there is no pain or ulceration. The most common location is in the palate; a plea is made for incisional biopsy of all oral lesions suspected of salivary gland origin. Survival rates show a progressive decrease with time, and there were no survivors beyond 20 years. In this study, there was a positive correlation between duration of the lesion before diagnosis and the salvage rate, but no correlation was found with the size of the presenting lesion."} {"id": "PMID:177924", "title": "Resection therapy of malignant tumours of the shoulder girdle.", "content": "Based on 30 resections in the shoulder region, operation techniques and results are precisely described with a view to curing and functioning. In the case of radical resections the rate of recurrences and cures in patients are the same as the rate of ablations. As the function of the hand is not impaired, this is a considerable advantage over amputations, although the cosmetic result of a resection may appear insufficient. In humerus resections bending contractures may frequently occur in the elbow joint and previous radiation may occasionally cause interior decubitus and exculceration. With an endoprosthetic replacement of the proximal humerous complications may be avoided, as experience with ceramic implants proved in 3 cases.", "contents": "Resection therapy of malignant tumours of the shoulder girdle. Based on 30 resections in the shoulder region, operation techniques and results are precisely described with a view to curing and functioning. In the case of radical resections the rate of recurrences and cures in patients are the same as the rate of ablations. As the function of the hand is not impaired, this is a considerable advantage over amputations, although the cosmetic result of a resection may appear insufficient. In humerus resections bending contractures may frequently occur in the elbow joint and previous radiation may occasionally cause interior decubitus and exculceration. With an endoprosthetic replacement of the proximal humerous complications may be avoided, as experience with ceramic implants proved in 3 cases."} {"id": "PMID:177927", "title": "[Regulation of the biosynthesis of macromolecules of the intercellular corneal matrix].", "content": "The influence of a 1M CaCl2 extract and of a collagenase digest of corneal stroma of the biosynthesis of the macromolecules of corneal stroma was investigated. Calf corneas were incubated \"in vitro\" with radioactive tracers (14C-L-proline; 3H-D-glucosamine or 35SO4) in the presence or absence of the above extracts. After incubation the corneas are submitted to a fractional extraction in order to separate the major macromolecular fractions of the stroma. An increase in incorporation of all tracers is observed in the 1M CaCl2 (CTC), TCA and urea-extracts (containing resp. the diffusible macromolecules, proteoglycans, polymeric collagen and structural glycoproteins) in the presence of the macromolecular extracts and also with the collagenase-hydrolysate of cornea. These results show the existence of a stimulation of the biosynthesis of intracellular matrix macromolecules of the cornea by corneal extracts, probably through positive \"feedback\" type of mechanism.", "contents": "[Regulation of the biosynthesis of macromolecules of the intercellular corneal matrix]. The influence of a 1M CaCl2 extract and of a collagenase digest of corneal stroma of the biosynthesis of the macromolecules of corneal stroma was investigated. Calf corneas were incubated \"in vitro\" with radioactive tracers (14C-L-proline; 3H-D-glucosamine or 35SO4) in the presence or absence of the above extracts. After incubation the corneas are submitted to a fractional extraction in order to separate the major macromolecular fractions of the stroma. An increase in incorporation of all tracers is observed in the 1M CaCl2 (CTC), TCA and urea-extracts (containing resp. the diffusible macromolecules, proteoglycans, polymeric collagen and structural glycoproteins) in the presence of the macromolecular extracts and also with the collagenase-hydrolysate of cornea. These results show the existence of a stimulation of the biosynthesis of intracellular matrix macromolecules of the cornea by corneal extracts, probably through positive \"feedback\" type of mechanism."} {"id": "PMID:177928", "title": "[Stereological analysis of the degranulation and the contraction of platelets. Application to the ultrastructural study of thrombin induced excretion in vitro].", "content": "A stereological model, which provides quantitative information on the morphology of the platelet release reaction as isolated from platelet aggregation, was developed for the human platelets separated from blood by Mustard's procedure. Three morphologically defined spaces (granules, surface-connected canalicular system S.C.S., cytoplasm) were used to characterize platelet degranulation (with the variation of the volume density of the granules) and contraction (with the variation of the volume density of both granules and S.C.S.). This model was applied to the evaluation of ultrastructural changes associated with the thrombin-induced release reaction. Degranulation and contraction were associated in the platelets which had been allowed to release for 1,5 and 150 sec. Under conditions of the study, prostaglandins E1 (10(-7) M) inhibited both degranulation and contraction (p less than 0,001). Aspirin (10(-4) M) only inhibited contraction (p less than 0.01) and dibutyryl-AMPc (10(-4)) only inhibited granulation (p less than 0,001).", "contents": "[Stereological analysis of the degranulation and the contraction of platelets. Application to the ultrastructural study of thrombin induced excretion in vitro]. A stereological model, which provides quantitative information on the morphology of the platelet release reaction as isolated from platelet aggregation, was developed for the human platelets separated from blood by Mustard's procedure. Three morphologically defined spaces (granules, surface-connected canalicular system S.C.S., cytoplasm) were used to characterize platelet degranulation (with the variation of the volume density of the granules) and contraction (with the variation of the volume density of both granules and S.C.S.). This model was applied to the evaluation of ultrastructural changes associated with the thrombin-induced release reaction. Degranulation and contraction were associated in the platelets which had been allowed to release for 1,5 and 150 sec. Under conditions of the study, prostaglandins E1 (10(-7) M) inhibited both degranulation and contraction (p less than 0,001). Aspirin (10(-4) M) only inhibited contraction (p less than 0.01) and dibutyryl-AMPc (10(-4)) only inhibited granulation (p less than 0,001)."} {"id": "PMID:177929", "title": "[Ultrastructure of the blood platelets in the newborn infant and in the young mongolian child. Study of 13 cases].", "content": "Blood platelets from infant and new born mongolians were examined and compared taking into consideration existing or non existing haematologic anomalies, such as transitory leucoblastosis with or without hyperthrombocytosis and acute leucosis without thrombopenia. These abnormalities were correlated with the analysis of control samples from haematologically normal new-born and premature children as well as samples from adult mongolian, patients with other chromosomal alterations (13-15, phi) and new-born or adults with thrombocytosis. The presence of dysmorphic platelets could be observed in variable degrees and numbers in all the mongolian samples. The characters of the morphologic abnormalities, constantly observed with variations due to pathological causes, denote either metabolic or structural thrombopathy.", "contents": "[Ultrastructure of the blood platelets in the newborn infant and in the young mongolian child. Study of 13 cases]. Blood platelets from infant and new born mongolians were examined and compared taking into consideration existing or non existing haematologic anomalies, such as transitory leucoblastosis with or without hyperthrombocytosis and acute leucosis without thrombopenia. These abnormalities were correlated with the analysis of control samples from haematologically normal new-born and premature children as well as samples from adult mongolian, patients with other chromosomal alterations (13-15, phi) and new-born or adults with thrombocytosis. The presence of dysmorphic platelets could be observed in variable degrees and numbers in all the mongolian samples. The characters of the morphologic abnormalities, constantly observed with variations due to pathological causes, denote either metabolic or structural thrombopathy."} {"id": "PMID:177930", "title": "[Herpes simplex virus in the saliva of immunosuppressed patients (author's transl)].", "content": "Attempts to isolate Herpes Simplex Virus (HSV) from the saliva of patients submitted to immunosuppressive drugs after renal transplantation were undertaken in the early part of the week following the graft. Results showed that the virus constantly appeared in the salvia of patients with serological positive tests to HSV. The presence of HSV was generally detected a few days before the appearance of the clinical disease.", "contents": "[Herpes simplex virus in the saliva of immunosuppressed patients (author's transl)]. Attempts to isolate Herpes Simplex Virus (HSV) from the saliva of patients submitted to immunosuppressive drugs after renal transplantation were undertaken in the early part of the week following the graft. Results showed that the virus constantly appeared in the salvia of patients with serological positive tests to HSV. The presence of HSV was generally detected a few days before the appearance of the clinical disease."} {"id": "PMID:177931", "title": "Lipid accumulation in a hepatocellular carcinoma associated with hypoglycaemia.", "content": "Four serial specimens over 18 months from a hepatocellular carcinoma associated with hypoglycaemia were studied by light microscopy. Ultrastructural study was possible for two of the specimens. Progressive fatty metamorphosis of the tumour cells was observed. The mechanism postulated was that of diversion of carbohydrate metabolism to lipogenesis due to enzyme disruption and dextrose infusion. The possibility of a defect in lipid transport was also considered.", "contents": "Lipid accumulation in a hepatocellular carcinoma associated with hypoglycaemia. Four serial specimens over 18 months from a hepatocellular carcinoma associated with hypoglycaemia were studied by light microscopy. Ultrastructural study was possible for two of the specimens. Progressive fatty metamorphosis of the tumour cells was observed. The mechanism postulated was that of diversion of carbohydrate metabolism to lipogenesis due to enzyme disruption and dextrose infusion. The possibility of a defect in lipid transport was also considered."} {"id": "PMID:177943", "title": "Cystic diseases of the kidney in children.", "content": "Many genetically determined cystic kidney disorders occur in children. Presenting manifestations related to the kidney include failure to thrive, abdominal enlargement or flank masses, progressive renal failure, or urinary tract infection. Radiological techniques often yield information helpful in establishing the type and extent of renal lesions. Cataloging the cystic renal disease in terms of genetic patterns, the involvement of liver or another organs, and the nature of the disorder of renal architecture is helpful in establishing the proper handling of affected children, and in genetic counseling.", "contents": "Cystic diseases of the kidney in children. Many genetically determined cystic kidney disorders occur in children. Presenting manifestations related to the kidney include failure to thrive, abdominal enlargement or flank masses, progressive renal failure, or urinary tract infection. Radiological techniques often yield information helpful in establishing the type and extent of renal lesions. Cataloging the cystic renal disease in terms of genetic patterns, the involvement of liver or another organs, and the nature of the disorder of renal architecture is helpful in establishing the proper handling of affected children, and in genetic counseling."} {"id": "PMID:177944", "title": "Evidence for the involvement of adenosine 3',5'-cyclic monophosphate in fever genesis.", "content": "In rabbit cerebrospinal fluid (CSF) during fever induced by endotoxins, myxoviruses, or endogenous pyrogen, concentrations of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and prostaglandin E (PGE) are about 2-fold higher in comparison to normal values. In endotoxin treated animals paracetamol reduced the fever reaction and both PGE and cyclic AMP levels. Administration of theophyllin together with endotoxin enhanced the fever reaction and cyclic AMP levels in CSF, but had no influence on stimulation of PGE synthesis. Following injection of PGE2 into the lateral cerebral ventricles increased cyclic AMP concentrations were found in CSF. The results suggest, that the pyrogenic effect of PGE is mediated by stimulation of cerebral cyclic AMP synthesis.", "contents": "Evidence for the involvement of adenosine 3',5'-cyclic monophosphate in fever genesis. In rabbit cerebrospinal fluid (CSF) during fever induced by endotoxins, myxoviruses, or endogenous pyrogen, concentrations of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and prostaglandin E (PGE) are about 2-fold higher in comparison to normal values. In endotoxin treated animals paracetamol reduced the fever reaction and both PGE and cyclic AMP levels. Administration of theophyllin together with endotoxin enhanced the fever reaction and cyclic AMP levels in CSF, but had no influence on stimulation of PGE synthesis. Following injection of PGE2 into the lateral cerebral ventricles increased cyclic AMP concentrations were found in CSF. The results suggest, that the pyrogenic effect of PGE is mediated by stimulation of cerebral cyclic AMP synthesis."} {"id": "PMID:177946", "title": "[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action].", "content": "Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens.", "contents": "[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action]. Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens."} {"id": "PMID:177950", "title": "[Association of nephrotic syndrome and Hodgkin's disease. Role of the Epstein-Barr virus].", "content": "The clinical association between glomerulonephrtis (GN) and malignant hematological disease is very rare. We report, in a 24 years old male, the occurrence of an apparently idiopathic nephrotic syndrome with minimal change glomerular lesions. This GN was in fact closely related to the progression of a stage 2A of Hodgkin's disease, following an infectious mononucleosis contracted one year ago. The nephrotic syndrome responded well to the therapy by Prednisone and Chlorambucil, and the complete remission persisted after eradication of Hodgkin's disease and despite early treatment discontinuation. Renal vein thrombosis, renal amyloidosis and renal interstitial infiltration with malignant cells were ruled out. Immunofluorescent and electron microscopy examination of the renal biopsies were consistent with, but not demonstrative of, an immune complex nephritis. Because of the chronological succession of infectious mononucleosis, Hodgkin's disease, and GN, we are stressing the possible oncogenic and immunogenic role of the Epstein-Barr virus.", "contents": "[Association of nephrotic syndrome and Hodgkin's disease. Role of the Epstein-Barr virus]. The clinical association between glomerulonephrtis (GN) and malignant hematological disease is very rare. We report, in a 24 years old male, the occurrence of an apparently idiopathic nephrotic syndrome with minimal change glomerular lesions. This GN was in fact closely related to the progression of a stage 2A of Hodgkin's disease, following an infectious mononucleosis contracted one year ago. The nephrotic syndrome responded well to the therapy by Prednisone and Chlorambucil, and the complete remission persisted after eradication of Hodgkin's disease and despite early treatment discontinuation. Renal vein thrombosis, renal amyloidosis and renal interstitial infiltration with malignant cells were ruled out. Immunofluorescent and electron microscopy examination of the renal biopsies were consistent with, but not demonstrative of, an immune complex nephritis. Because of the chronological succession of infectious mononucleosis, Hodgkin's disease, and GN, we are stressing the possible oncogenic and immunogenic role of the Epstein-Barr virus."} {"id": "PMID:177962", "title": "Viral infections that affect the fetus.", "content": "Several viral infections besides rubella are known to cause fetal anomalies and disease. Cytomegalovirus, for example, may adversely affect the fetus in a number of ways. Either herpesvirus or hepatitis B virus is transmissible from mother to offspring. Viruses whose potential for fetal harm is less clear are those of varicella, mumps, and influenza.", "contents": "Viral infections that affect the fetus. Several viral infections besides rubella are known to cause fetal anomalies and disease. Cytomegalovirus, for example, may adversely affect the fetus in a number of ways. Either herpesvirus or hepatitis B virus is transmissible from mother to offspring. Viruses whose potential for fetal harm is less clear are those of varicella, mumps, and influenza."} {"id": "PMID:177963", "title": "Not-so-hyper hyperlipo-proteinemia and coronary artery disease.", "content": "Atherosclerosis is the leading cause of death in the United States, and its prevention is now a primary goal of health care personnel. Knowledge of the early history of the disease, which would be particularly helpful in determing its pathogenesis, is still lacking. Studies are only now beginning to be directed at younger individuals without clinical evidence of disease. Hyperlipoproteinemia has been considered a definite risk factor for atherosclerosis for some years, but because of the difficulty involved in relating specific lipid abnormalities to the extent of atherosclerosis in a given patient, unequivocal proof of its role is lacking. Serum lipid and lipoprotein levels used to define hyperlipoproteinemia in the United States are derived from a system in which 95% of the population are regarded as having normal levels. The cut points are set far too high. Mild hyperlipoproteinemia is rampant in this country, as is coronary artery disease, and from the evidence now available, it seems reasonable to try to lower the incidence of the latter by reducing blood lipid levels of the entire population through dietary modification.", "contents": "Not-so-hyper hyperlipo-proteinemia and coronary artery disease. Atherosclerosis is the leading cause of death in the United States, and its prevention is now a primary goal of health care personnel. Knowledge of the early history of the disease, which would be particularly helpful in determing its pathogenesis, is still lacking. Studies are only now beginning to be directed at younger individuals without clinical evidence of disease. Hyperlipoproteinemia has been considered a definite risk factor for atherosclerosis for some years, but because of the difficulty involved in relating specific lipid abnormalities to the extent of atherosclerosis in a given patient, unequivocal proof of its role is lacking. Serum lipid and lipoprotein levels used to define hyperlipoproteinemia in the United States are derived from a system in which 95% of the population are regarded as having normal levels. The cut points are set far too high. Mild hyperlipoproteinemia is rampant in this country, as is coronary artery disease, and from the evidence now available, it seems reasonable to try to lower the incidence of the latter by reducing blood lipid levels of the entire population through dietary modification."} {"id": "PMID:177958", "title": "Histochemistry of hormonally active ovarian tumors.", "content": "Thirty-five ovarian tumors were examined (7 granulosa-cell tumors, 2 thecomas, 4 dysgerminomas, 6 mucinous cystadenomas, 10 serous cystadenomas, 2 adenocarcinomas, 3 Krukenberg tumors and 1 early embryonic tumor). The granulosa-cell tumors showed high activity of alpha-glycerophosphate dehydrogenase, and the changed cells of their stroma--that of glucose-6 phosphate and isocitrate dehydrogenases. The activity of the latter enzymes was striking also in thecomas. Dysgerminomas showed high alkaline phosphatase, acid phosphatase and nonspecific esterase activities. The authors emphasize the role of stromal cells in the hormonal activity of ovarian neoplasms.", "contents": "Histochemistry of hormonally active ovarian tumors. Thirty-five ovarian tumors were examined (7 granulosa-cell tumors, 2 thecomas, 4 dysgerminomas, 6 mucinous cystadenomas, 10 serous cystadenomas, 2 adenocarcinomas, 3 Krukenberg tumors and 1 early embryonic tumor). The granulosa-cell tumors showed high activity of alpha-glycerophosphate dehydrogenase, and the changed cells of their stroma--that of glucose-6 phosphate and isocitrate dehydrogenases. The activity of the latter enzymes was striking also in thecomas. Dysgerminomas showed high alkaline phosphatase, acid phosphatase and nonspecific esterase activities. The authors emphasize the role of stromal cells in the hormonal activity of ovarian neoplasms."} {"id": "PMID:177959", "title": "Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. I. Adenohypophysis.", "content": "Ultrastructural changes in the secretory lobe of rat hypophysis following bilateral adrenalectomy and a single subcutaneous administration of 1 i.u. of ACTH were studied. Both after adrenalectomy and ACTH administration, ultrastructural changes were found to appear exclusively in one type of secretory cells. After adrenalectomy, pictures were found in these cells indicative of increased synthesis of the secretory granulations. One hour after the administration of ACTH the ACTH-secreting cells showed features of decreased secretory activity.", "contents": "Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. I. Adenohypophysis. Ultrastructural changes in the secretory lobe of rat hypophysis following bilateral adrenalectomy and a single subcutaneous administration of 1 i.u. of ACTH were studied. Both after adrenalectomy and ACTH administration, ultrastructural changes were found to appear exclusively in one type of secretory cells. After adrenalectomy, pictures were found in these cells indicative of increased synthesis of the secretory granulations. One hour after the administration of ACTH the ACTH-secreting cells showed features of decreased secretory activity."} {"id": "PMID:177964", "title": "Fibroadenoma of the female breast. Some epidemiologic surprises.", "content": "In a study of 70 cases of fibroadenoma of the female breast, two ages of peak incidence were recorded, one of them in the late 20s to early 30s and a second in the late 40s to early 50s. At the time of diagnosis, the lesions usually were less than 3.0 cm in diameter. Almost two thirds of the tumors were situated in the lateral quadrants of the breast. Incidence of fibroadenoma was significantly higher among parous females tham among nulliparas. Review of family histories showed a remarkably high incidence of breast disease of all types in the mothers and sisters of the patients studied. An inordinately high proportion of patients under 40 years of age were nonwhite. Recurrences and multiple lesions were much more frequent in patients over 40. \"Recurrences\" are undoubtedly serial presentations of multicentric lesions.", "contents": "Fibroadenoma of the female breast. Some epidemiologic surprises. In a study of 70 cases of fibroadenoma of the female breast, two ages of peak incidence were recorded, one of them in the late 20s to early 30s and a second in the late 40s to early 50s. At the time of diagnosis, the lesions usually were less than 3.0 cm in diameter. Almost two thirds of the tumors were situated in the lateral quadrants of the breast. Incidence of fibroadenoma was significantly higher among parous females tham among nulliparas. Review of family histories showed a remarkably high incidence of breast disease of all types in the mothers and sisters of the patients studied. An inordinately high proportion of patients under 40 years of age were nonwhite. Recurrences and multiple lesions were much more frequent in patients over 40. \"Recurrences\" are undoubtedly serial presentations of multicentric lesions."} {"id": "PMID:177960", "title": "Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. II. Neurohypophysis.", "content": "Electron-microscopic changes in the neural lobe of the rat hypophysis following adrenalectomy and a single administration of ACTH were studied. Twelve hours after adrenalectomy, a decrease in the amount of neurosecretory substances was observed, manifested by a small number of elementary granules of high electron density and, by the appearance of a great number of optically empty vesicles and masses of membrane-free material of low electron density. The increased secretion of neurosecretory substances after adrenalectomy seems to be related to the increased requirement of the organism for the ACTH-releasing factor. One hour after administration of ACTH, a picture was observed suggestive of the release of neurosecretory substances from the neural lobe fibers, which is probably connected with disturbances in the composition of blood electrolytes accompanying the excess of adrenocortical hormones.", "contents": "Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. II. Neurohypophysis. Electron-microscopic changes in the neural lobe of the rat hypophysis following adrenalectomy and a single administration of ACTH were studied. Twelve hours after adrenalectomy, a decrease in the amount of neurosecretory substances was observed, manifested by a small number of elementary granules of high electron density and, by the appearance of a great number of optically empty vesicles and masses of membrane-free material of low electron density. The increased secretion of neurosecretory substances after adrenalectomy seems to be related to the increased requirement of the organism for the ACTH-releasing factor. One hour after administration of ACTH, a picture was observed suggestive of the release of neurosecretory substances from the neural lobe fibers, which is probably connected with disturbances in the composition of blood electrolytes accompanying the excess of adrenocortical hormones."} {"id": "PMID:177966", "title": "Communication and cancer patients. A new form of immediate hospital discharge letter.", "content": "We present the favourable response we have received from general practitioners to our 'immediate discharge letter' relating to cancer patients.", "contents": "Communication and cancer patients. A new form of immediate hospital discharge letter. We present the favourable response we have received from general practitioners to our 'immediate discharge letter' relating to cancer patients."} {"id": "PMID:177967", "title": "Hyperhidrosis and hypohidrosis.", "content": "Sweating has an important physiological function concerned with both temperature and fluid balance. Hypohidrosis is uncommon and rarely recognized by the patient. It usually represents damage to the central nervous system or peripheral nerves. Hyperhidrosis may be a feature of general medical diseases such as thyrotoxicosis and fevers. It may also be due to damage of the central of peripheral sympathetic nerves. Localized hyperhidrosis tends to occur on the palms, the soles, the axillae and, to a lesser extent, the face. Treatment of local hyperhidrosis with topical aluminium salts, or with topical or oral anticholinergics, may help some patients but surgery may be indicated in those with severe hyperhidrosis.", "contents": "Hyperhidrosis and hypohidrosis. Sweating has an important physiological function concerned with both temperature and fluid balance. Hypohidrosis is uncommon and rarely recognized by the patient. It usually represents damage to the central nervous system or peripheral nerves. Hyperhidrosis may be a feature of general medical diseases such as thyrotoxicosis and fevers. It may also be due to damage of the central of peripheral sympathetic nerves. Localized hyperhidrosis tends to occur on the palms, the soles, the axillae and, to a lesser extent, the face. Treatment of local hyperhidrosis with topical aluminium salts, or with topical or oral anticholinergics, may help some patients but surgery may be indicated in those with severe hyperhidrosis."} {"id": "PMID:177969", "title": "Functional incorporation of ganglioside into intact cells: induction of choleragen responsiveness.", "content": "NCTC 2071 cells are unable to synthesize the monosialoganglioside GM1. When grown in chemically defined medium these cells contained no detectable GM1 and did not accumulate 3': 5'-cyclic AMP in response to choleragen. Incubation of the cells with [3H]GM1 permitted quantification of ganglioside uptake which was dependent on time and concentration of [3H]GM1 in the medium. Responsiveness to choleragen was demonstrated with binding of as few as 17,000 molecules of [3H]GM1 per cell; a maximal response was observed with 10(5) molecules per cell. With increasing cellular content of GM1, the rate of rise in intracellular cyclic AMP in response to choleragen was increased. With greater than 1 X 10(5) molecules of GM1 per cell, the delay between addition of choleragen and the cyclic AMP response was inversely proportional to choleragen concentration; less than 250 molecules of choleragen per cell caused a significant increase in cyclic AMP after 8 hr of incubation. Although the responsiveness of intact cells to choleragen was dependent on GM1, choleragen activation of adenylate cyclase in homogenates with 0.6 mM NAD was independent of added ganglioside. These observations are consistent with the view that exogenous ganglioside GM1 can be functionally integrated into the surface membrane of intact cells and serve as the choleragen receptor. Furthermore, although exogenous GM1 is required for choleragen responsiveness in intact cells, the ganglioside does not play an obligatory role in cell homogenates, where the surface receptor can presumably be bypassed.", "contents": "Functional incorporation of ganglioside into intact cells: induction of choleragen responsiveness. NCTC 2071 cells are unable to synthesize the monosialoganglioside GM1. When grown in chemically defined medium these cells contained no detectable GM1 and did not accumulate 3': 5'-cyclic AMP in response to choleragen. Incubation of the cells with [3H]GM1 permitted quantification of ganglioside uptake which was dependent on time and concentration of [3H]GM1 in the medium. Responsiveness to choleragen was demonstrated with binding of as few as 17,000 molecules of [3H]GM1 per cell; a maximal response was observed with 10(5) molecules per cell. With increasing cellular content of GM1, the rate of rise in intracellular cyclic AMP in response to choleragen was increased. With greater than 1 X 10(5) molecules of GM1 per cell, the delay between addition of choleragen and the cyclic AMP response was inversely proportional to choleragen concentration; less than 250 molecules of choleragen per cell caused a significant increase in cyclic AMP after 8 hr of incubation. Although the responsiveness of intact cells to choleragen was dependent on GM1, choleragen activation of adenylate cyclase in homogenates with 0.6 mM NAD was independent of added ganglioside. These observations are consistent with the view that exogenous ganglioside GM1 can be functionally integrated into the surface membrane of intact cells and serve as the choleragen receptor. Furthermore, although exogenous GM1 is required for choleragen responsiveness in intact cells, the ganglioside does not play an obligatory role in cell homogenates, where the surface receptor can presumably be bypassed."} {"id": "PMID:177970", "title": "Synthetic hexapeptide substrates and inhibitors of 3':5'-cyclic AMP-dependent protein kinase.", "content": "The substrate specificity of the catalytic subunit of rabbit skeletal muscle 3': 5'-cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP: protein phosphotransferase) has been studied using the synthetic peptide Arg-Gly-Tyr-Ser-Leu-Gly corresponding to the sequence around serine 24, a phosphorylation site in reduced, carboxymethylated, maleylated (RCMM) chicken egg white lysozyme. This peptide served as a substrate for the enzyme and exhibited a 6-fold higher Vmax and a 100-fold higher Km than RCMM-lysozyme. Replacement of the arginine with glycine, histidine, or lysine resulted in a dramatic reduction in the Vmax. These results support the concept that arginine is an important residue in determining the substrate specificity of the protein kinase, predominantly influencing the Vmax of the phosphorylation reaction. Two synthetic peptides in which serine was replaced by an alanine acted as competitive inhibitors of phosphorylation of the synthetic peptide substrate and RCMM-lysozyme.", "contents": "Synthetic hexapeptide substrates and inhibitors of 3':5'-cyclic AMP-dependent protein kinase. The substrate specificity of the catalytic subunit of rabbit skeletal muscle 3': 5'-cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP: protein phosphotransferase) has been studied using the synthetic peptide Arg-Gly-Tyr-Ser-Leu-Gly corresponding to the sequence around serine 24, a phosphorylation site in reduced, carboxymethylated, maleylated (RCMM) chicken egg white lysozyme. This peptide served as a substrate for the enzyme and exhibited a 6-fold higher Vmax and a 100-fold higher Km than RCMM-lysozyme. Replacement of the arginine with glycine, histidine, or lysine resulted in a dramatic reduction in the Vmax. These results support the concept that arginine is an important residue in determining the substrate specificity of the protein kinase, predominantly influencing the Vmax of the phosphorylation reaction. Two synthetic peptides in which serine was replaced by an alanine acted as competitive inhibitors of phosphorylation of the synthetic peptide substrate and RCMM-lysozyme."} {"id": "PMID:177971", "title": "Construction and propagation of a defective simian virus 40 genome bearing an operator from bacteriophage lambda.", "content": "A 2400 base pair DNA segment containing the leftward operator (OL) of phage lambda was covalently joined in vitro to a fragment of simian virus 40 (SV40) DNA harboring the SV40 replication origin. The recombinant molecule was propagated in the presence of helper wild-type SV40 DNA in monkey kidney cells and partially cloned by an infectious center procedure. After propagation in monkey cells and purification, the hybrid DNA could be distinguished from wild-type SV40 DNA by its shortened length (about 80% that of SV40), specific hybridization to denatured lambda DNA immobilized on filters, specific affinity for lambda repressor, and preservation of a large part (about 2300 base pairs) of the lambda immunity region as determined by restriction nuclease cleavage patterns and electron microscopic heteroduplex analysis. These results indicate that defective SV40 replicons can serve as vectors for propagating foreign DNA in mammalian cells.", "contents": "Construction and propagation of a defective simian virus 40 genome bearing an operator from bacteriophage lambda. A 2400 base pair DNA segment containing the leftward operator (OL) of phage lambda was covalently joined in vitro to a fragment of simian virus 40 (SV40) DNA harboring the SV40 replication origin. The recombinant molecule was propagated in the presence of helper wild-type SV40 DNA in monkey kidney cells and partially cloned by an infectious center procedure. After propagation in monkey cells and purification, the hybrid DNA could be distinguished from wild-type SV40 DNA by its shortened length (about 80% that of SV40), specific hybridization to denatured lambda DNA immobilized on filters, specific affinity for lambda repressor, and preservation of a large part (about 2300 base pairs) of the lambda immunity region as determined by restriction nuclease cleavage patterns and electron microscopic heteroduplex analysis. These results indicate that defective SV40 replicons can serve as vectors for propagating foreign DNA in mammalian cells."} {"id": "PMID:177972", "title": "Distribution of envelope-specific and sarcoma-specific nucleotide sequences from different parents in the RNAs of avian tumor virus recombinants.", "content": "The distribution of leukosis-virus- and sarcoma-virus-specific oligonucleotide sequences was investigated in the RNAs of viral recombinants selected for an envelope gene (env) from a leukosis parent and a sarcoma gene (src) from a sarcoma parent. For this purpose 20 to 30 RNase-T1-resistant oligonucleotides were chemically analyzed and mapped within the 10,000 nucleotides of each viral RNA relative to the 3'-poly(A) end. The resulting oligonucleotide maps were compared. Proceeding from the 3' to the 5' end, the maps of four recombinants contained: (i) in a segment of 2000 nucleotides, three to four src-specific oligonucleotides, so identified because they were shared only with the sarcoma parent; and (ii) in a segment of 8000 nucleotides, 20 oligonucleotides shared with the leukosis parent, of which six to seven were also shared with the sarcoma parent. Two other recombinants contained: (1) in a segment of 2000 (one) or 3000 (the other) nucleotides, three src-specific oligonucleotides; (ii) in a segment of 3000 (one) or 2000 (the other) nucleotides, five (one) or four (the other) oligonucleotides, all or some of which are env-specific, because they were shared with the leukosis parent; (iii) in a segment of 5000 nucleotides (both), 11 functionally unidentified sarcoma-virus-derived oligonucleotides, of which seven were also shared with the leukosis parent. The map locations of parental oligonucleotides were not changed in recombinants and all viral strains tested shared six to eight highly conserved oligonucleotides at equivalent map locations. The partial map -env-src-poly(A) emerged from the analyses of these recombinants.", "contents": "Distribution of envelope-specific and sarcoma-specific nucleotide sequences from different parents in the RNAs of avian tumor virus recombinants. The distribution of leukosis-virus- and sarcoma-virus-specific oligonucleotide sequences was investigated in the RNAs of viral recombinants selected for an envelope gene (env) from a leukosis parent and a sarcoma gene (src) from a sarcoma parent. For this purpose 20 to 30 RNase-T1-resistant oligonucleotides were chemically analyzed and mapped within the 10,000 nucleotides of each viral RNA relative to the 3'-poly(A) end. The resulting oligonucleotide maps were compared. Proceeding from the 3' to the 5' end, the maps of four recombinants contained: (i) in a segment of 2000 nucleotides, three to four src-specific oligonucleotides, so identified because they were shared only with the sarcoma parent; and (ii) in a segment of 8000 nucleotides, 20 oligonucleotides shared with the leukosis parent, of which six to seven were also shared with the sarcoma parent. Two other recombinants contained: (1) in a segment of 2000 (one) or 3000 (the other) nucleotides, three src-specific oligonucleotides; (ii) in a segment of 3000 (one) or 2000 (the other) nucleotides, five (one) or four (the other) oligonucleotides, all or some of which are env-specific, because they were shared with the leukosis parent; (iii) in a segment of 5000 nucleotides (both), 11 functionally unidentified sarcoma-virus-derived oligonucleotides, of which seven were also shared with the leukosis parent. The map locations of parental oligonucleotides were not changed in recombinants and all viral strains tested shared six to eight highly conserved oligonucleotides at equivalent map locations. The partial map -env-src-poly(A) emerged from the analyses of these recombinants."} {"id": "PMID:177973", "title": "Deficiency in histone acetylation in nontransforming host range mutants of polyoma virus.", "content": "Histones H3 and H4 derived from transforming wild-type polyoma and simian virus 40 particles show extensive acetylation compared to the histones of the host cells. The same histone fractions derived from nontransforming host range mutants of polyoma virus fail to show this high degree of acetylation.", "contents": "Deficiency in histone acetylation in nontransforming host range mutants of polyoma virus. Histones H3 and H4 derived from transforming wild-type polyoma and simian virus 40 particles show extensive acetylation compared to the histones of the host cells. The same histone fractions derived from nontransforming host range mutants of polyoma virus fail to show this high degree of acetylation."} {"id": "PMID:177974", "title": "Two forms of simian-virus-40-specific T-antigen in abortive and lytic infection.", "content": "Simian-virus-40-specific T-antigen was isolated by immunoprecipitation. From other studies we have proof that the T-antigen described in this work is coded by the viral DNA. The molecular weight estimated from electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels of T-antigen isolated from nonpermissive mouse cells in abortive infection is 86,000 and from permissive monkey cells in lytic infection is 82,000. The 86 kilodalton T-antigen is readily converted in vitro into an 82 kilodalton form by incubation with extracts from permissive monkey cells but not with extracts from nonpermissive mouse or hamster cells. This and the results of fingerprinting analysis of tryptic peptides suggest that T-antigen may be processed in permissive cells.", "contents": "Two forms of simian-virus-40-specific T-antigen in abortive and lytic infection. Simian-virus-40-specific T-antigen was isolated by immunoprecipitation. From other studies we have proof that the T-antigen described in this work is coded by the viral DNA. The molecular weight estimated from electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels of T-antigen isolated from nonpermissive mouse cells in abortive infection is 86,000 and from permissive monkey cells in lytic infection is 82,000. The 86 kilodalton T-antigen is readily converted in vitro into an 82 kilodalton form by incubation with extracts from permissive monkey cells but not with extracts from nonpermissive mouse or hamster cells. This and the results of fingerprinting analysis of tryptic peptides suggest that T-antigen may be processed in permissive cells."} {"id": "PMID:177975", "title": "Integrated simian virus 40 sequences in transformed cell DNA: analysis using restriction endonucleases.", "content": "The DNAs from five independent simian virus 40 (SV40) transformants of the BALB/c3T3 mouse cell line were digested with either the HpaII or the BamHI restriction endonuclease and the resulting fragments were fractionated by gel electrophoresis. The DNA fragments were denatured in situ in the gel and transferred to a membrane filter. Fragments containing viral DNA were detected by hybridization with high specific activity 32P-labeled SV40 complementary RNA (cRNA) synthesized in vitro. Each of the lines yielded a small number of fragments containing SV40 DNA and the fragments from each line were different. This observation shows that the structure of the integrated SV40 DNA and/or its location in the host DNA are different in each line.", "contents": "Integrated simian virus 40 sequences in transformed cell DNA: analysis using restriction endonucleases. The DNAs from five independent simian virus 40 (SV40) transformants of the BALB/c3T3 mouse cell line were digested with either the HpaII or the BamHI restriction endonuclease and the resulting fragments were fractionated by gel electrophoresis. The DNA fragments were denatured in situ in the gel and transferred to a membrane filter. Fragments containing viral DNA were detected by hybridization with high specific activity 32P-labeled SV40 complementary RNA (cRNA) synthesized in vitro. Each of the lines yielded a small number of fragments containing SV40 DNA and the fragments from each line were different. This observation shows that the structure of the integrated SV40 DNA and/or its location in the host DNA are different in each line."} {"id": "PMID:177976", "title": "Control of protein synthesis in reticulocyte lysates: effects of 3':5'-cyclic AMP, ATP, and GTP on inhibitions induced by hemedeficiency, double-stranded RNA, and a reticulocyte translationa inhibitor.", "content": "Protein chain initiation in reticulocyte lysates is inhibited by (a) heme-deficiency, (b) low levels of double-stranded RNA, and (c) a purified translational inhibitor isolated from heme-deficient lysates. Previous studies have shown that the inhibitions produced by heme-deficiency and double-stranded RNA are prevented by 3': 5'-cyclic AMP, and that GTP, but not ATP, prevents the inhibition of heme-deficiency. In view of the recent finding that the inhibitor purified from heme-deficient lysates is associated with a protein kinase which appears to be involved in the mechanism of inhibition, the effects of cyclic AMP, GTP, and ATP on the three modes of inhibition were examines. In all three types of inhibition, cyclic AMP or GTP (a) prevents the onset of inhibition when added at zero time, and (b) restores protein synthesis in inhibited lysates. In contrast to these effects, ATP potentiates each inhibition, and blocks reversal of inhibition by cyclic AMP or GTP. On the basis of these and earlier findings, we propose that (a) these inhibitions involve the phosphorylation by protein kinases of the Met-tRNAf binding factor and/or a related site(s) on the 40S ribosomal subunit; and (b) cyclic AMP, GTP, and ATP exert their effects by their actions on this phosphorylation mechanism.", "contents": "Control of protein synthesis in reticulocyte lysates: effects of 3':5'-cyclic AMP, ATP, and GTP on inhibitions induced by hemedeficiency, double-stranded RNA, and a reticulocyte translationa inhibitor. Protein chain initiation in reticulocyte lysates is inhibited by (a) heme-deficiency, (b) low levels of double-stranded RNA, and (c) a purified translational inhibitor isolated from heme-deficient lysates. Previous studies have shown that the inhibitions produced by heme-deficiency and double-stranded RNA are prevented by 3': 5'-cyclic AMP, and that GTP, but not ATP, prevents the inhibition of heme-deficiency. In view of the recent finding that the inhibitor purified from heme-deficient lysates is associated with a protein kinase which appears to be involved in the mechanism of inhibition, the effects of cyclic AMP, GTP, and ATP on the three modes of inhibition were examines. In all three types of inhibition, cyclic AMP or GTP (a) prevents the onset of inhibition when added at zero time, and (b) restores protein synthesis in inhibited lysates. In contrast to these effects, ATP potentiates each inhibition, and blocks reversal of inhibition by cyclic AMP or GTP. On the basis of these and earlier findings, we propose that (a) these inhibitions involve the phosphorylation by protein kinases of the Met-tRNAf binding factor and/or a related site(s) on the 40S ribosomal subunit; and (b) cyclic AMP, GTP, and ATP exert their effects by their actions on this phosphorylation mechanism."} {"id": "PMID:177977", "title": "Transcription-translation and translation-messenger RNA decay coupling: separate mechanisms for different messengers.", "content": "Antibiotics were used to inhibit protein synthesis at specific steps in the biosynthetic pathway. In this way, it was possible to study the coupling of protein synthesis to the accumulation of biologically active mRNA in T4-infected Escherichia coli. Functional mRNA for the phage enzymes deoxynucleotide kinase (EC 2.7.4.4; ATP: nucleoside monophosphate phosphotransferase or nucleosidemonophosphate kinase) and alpha-glucosyltransferase (EC 2.4.1.5; 1, 4-alpha-D-glucan: 1, 6-alpha-D-glucan 6-alpha-glucosyltransferase or dextrin dextranase) accumulated during inhibition of protein synthesis irrespective of the step in the synthesis of protein that was blocked. Under these conditions, however, the rate of mRNA synthesis for both enzymes was significantly inhibited. In contrast, the rate of degradation of these mRNAs was markedly dependent on the step in protein synthesis that was inhibited. That is, the site for mRNase action was different for each message. The most important step in protein synthesis required for the stability of deoxynucleotide kinase mRNA is the initiation step. A single ribosome bound to the 5' end of the deoxynucleotide kinase mRNA can stabilize the molecule. On the other hand, the initiation event does not seem to be important for stabilizing the alpha-glucosyltransferase mRNA. Instead, a high ribosome denisty on the alpha-glucosyltransferase messenger is required to achieve significant stability. Therefore, in studying messenger metabolism, it is important to focus on the functional stability of specific mRNAs instead of on total messenger since each mRNA can be metabolized differently.", "contents": "Transcription-translation and translation-messenger RNA decay coupling: separate mechanisms for different messengers. Antibiotics were used to inhibit protein synthesis at specific steps in the biosynthetic pathway. In this way, it was possible to study the coupling of protein synthesis to the accumulation of biologically active mRNA in T4-infected Escherichia coli. Functional mRNA for the phage enzymes deoxynucleotide kinase (EC 2.7.4.4; ATP: nucleoside monophosphate phosphotransferase or nucleosidemonophosphate kinase) and alpha-glucosyltransferase (EC 2.4.1.5; 1, 4-alpha-D-glucan: 1, 6-alpha-D-glucan 6-alpha-glucosyltransferase or dextrin dextranase) accumulated during inhibition of protein synthesis irrespective of the step in the synthesis of protein that was blocked. Under these conditions, however, the rate of mRNA synthesis for both enzymes was significantly inhibited. In contrast, the rate of degradation of these mRNAs was markedly dependent on the step in protein synthesis that was inhibited. That is, the site for mRNase action was different for each message. The most important step in protein synthesis required for the stability of deoxynucleotide kinase mRNA is the initiation step. A single ribosome bound to the 5' end of the deoxynucleotide kinase mRNA can stabilize the molecule. On the other hand, the initiation event does not seem to be important for stabilizing the alpha-glucosyltransferase mRNA. Instead, a high ribosome denisty on the alpha-glucosyltransferase messenger is required to achieve significant stability. Therefore, in studying messenger metabolism, it is important to focus on the functional stability of specific mRNAs instead of on total messenger since each mRNA can be metabolized differently."} {"id": "PMID:177978", "title": "Dephosphorylation of nonhistone proteins specifically alters the pattern of gene transcription in reconstituted chromatin.", "content": "A nonhistone phosphatase devoid of detectable protease activity has been purified from nuclear sap by chromatography on DEAE-Sephadex. After linkage to an insoluble agarose matrix, this enzyme was used to dephosphorylate nonhistone proteins obtained from S-phase HeLa cells. Chromatin reconstituted with these dephosphorylated proteins exhibited roughly a 50% reduction in the overall number of initiation sites available for transcription when compared to controls. Specific measurements of transcription of histone genes with use of a complementary DNA probe showed that genes coding for histones are preferentially inhibited after nonhistone dephosphorylation. These results provide the first direct support for the theory that phosphorylation of nonhistone proteins is involved in regulating the availability of individual genes for transcription.", "contents": "Dephosphorylation of nonhistone proteins specifically alters the pattern of gene transcription in reconstituted chromatin. A nonhistone phosphatase devoid of detectable protease activity has been purified from nuclear sap by chromatography on DEAE-Sephadex. After linkage to an insoluble agarose matrix, this enzyme was used to dephosphorylate nonhistone proteins obtained from S-phase HeLa cells. Chromatin reconstituted with these dephosphorylated proteins exhibited roughly a 50% reduction in the overall number of initiation sites available for transcription when compared to controls. Specific measurements of transcription of histone genes with use of a complementary DNA probe showed that genes coding for histones are preferentially inhibited after nonhistone dephosphorylation. These results provide the first direct support for the theory that phosphorylation of nonhistone proteins is involved in regulating the availability of individual genes for transcription."} {"id": "PMID:177979", "title": "Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts.", "content": "We have isolated the major cell surface glycoprotein of chick embryo fibroblasts, CSP, and added it to a variety of transformed cells in vitro. The transformed cells become more elongated, often more flattened, and show increased adhesion to the substratum. Several transformed cell lines also align in striking parallel arrays. This alignment is characterized by a decrease in the amount of nuclear overlapping, probably indicating restoration of contact inhibition of movement. The morphological changes are antagonized by antibody to CSP. These effects of CSP are not associated with an elevation of cellular 3':5'-cyclic AMP. Moreover, the morphological reversion is not accompanied by an alteration in growth properties. Our results are consistent with a role for CSP in cell adhesion and morphology but not in growth control.", "contents": "Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts. We have isolated the major cell surface glycoprotein of chick embryo fibroblasts, CSP, and added it to a variety of transformed cells in vitro. The transformed cells become more elongated, often more flattened, and show increased adhesion to the substratum. Several transformed cell lines also align in striking parallel arrays. This alignment is characterized by a decrease in the amount of nuclear overlapping, probably indicating restoration of contact inhibition of movement. The morphological changes are antagonized by antibody to CSP. These effects of CSP are not associated with an elevation of cellular 3':5'-cyclic AMP. Moreover, the morphological reversion is not accompanied by an alteration in growth properties. Our results are consistent with a role for CSP in cell adhesion and morphology but not in growth control."} {"id": "PMID:177980", "title": "Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds.", "content": "The murine-virus-infected erythroleukemia cell system provides an opportunity to examine regulatory mechanisms controlling cytodifferentiation. A cloned cell line (DR10c3) resistant to the erythropoiesis-inducing effect of dimethylsulfoxide (Me2SO) was isolated from the Me2SO-sensitive line DS19. DR10c3 is characterized as follows: (1) the uptake of [3H]Me2SO is similar to that in DS19; (2) cell growth with and without Me2SO is similar to that of DS19; (3) resistance is relatively stable; (4) the karyotype of DR10c3 reveals an average loss of five chromosomes per cell, but is otherwise similar to that of DS19; (5) total protein and globin synthesis by cells cultured 4 days with or without Me2SO is similar to these syntheses in DS19 cultured without Me2SO; (6) virtually no globin mRNA is detectable after 3 days in Me2SO, as assayed both by RNA-complementary DNA hybridization and by the heterologous cell-free protein-synthesizing system; (7) other polar compounds, N-methylpyrrolidinone, 1-methyl-2-piperidone, N, N-dimethylacetamide, and N-methylacetamide, induce erythroid differentiation in DR10c3, and the accumulation of alpha- and beta-globin chains is indistinguishable from that in DS19; and (8) the concentration optima for induction of differentiation by all these compounds are identical for DR10c3 and DS19.", "contents": "Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds. The murine-virus-infected erythroleukemia cell system provides an opportunity to examine regulatory mechanisms controlling cytodifferentiation. A cloned cell line (DR10c3) resistant to the erythropoiesis-inducing effect of dimethylsulfoxide (Me2SO) was isolated from the Me2SO-sensitive line DS19. DR10c3 is characterized as follows: (1) the uptake of [3H]Me2SO is similar to that in DS19; (2) cell growth with and without Me2SO is similar to that of DS19; (3) resistance is relatively stable; (4) the karyotype of DR10c3 reveals an average loss of five chromosomes per cell, but is otherwise similar to that of DS19; (5) total protein and globin synthesis by cells cultured 4 days with or without Me2SO is similar to these syntheses in DS19 cultured without Me2SO; (6) virtually no globin mRNA is detectable after 3 days in Me2SO, as assayed both by RNA-complementary DNA hybridization and by the heterologous cell-free protein-synthesizing system; (7) other polar compounds, N-methylpyrrolidinone, 1-methyl-2-piperidone, N, N-dimethylacetamide, and N-methylacetamide, induce erythroid differentiation in DR10c3, and the accumulation of alpha- and beta-globin chains is indistinguishable from that in DS19; and (8) the concentration optima for induction of differentiation by all these compounds are identical for DR10c3 and DS19."} {"id": "PMID:177981", "title": "Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases.", "content": "The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3', 5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[a]pyrene hydroxylase, as well as the amount of cytochrome P-448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drug-metabolizing enzymes include the following sequence of events: (1) increase in cAMP concentration and/or activation of cAMP-dependent protein kinase; (2) induction of ornithine decarboxylase; and, (3) induction of drug-metabolizing enzymes.", "contents": "Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases. The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3', 5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[a]pyrene hydroxylase, as well as the amount of cytochrome P-448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drug-metabolizing enzymes include the following sequence of events: (1) increase in cAMP concentration and/or activation of cAMP-dependent protein kinase; (2) induction of ornithine decarboxylase; and, (3) induction of drug-metabolizing enzymes."} {"id": "PMID:177982", "title": "A differentiation stimulating factor induces cell sensitivity to 3':5'-cyclic AMP pulses in dictyostelium discoideum.", "content": "During the first few hours of starvation, Dictyostelium discoideum amoebae excrete a macromolecule, probably a glycoprotein, which stimulates cell differentiation to aggregation competence. 3':5'-Cyclic AMP pulses, which mimic the chemotactic signal, and this factor (differentiation stimulating factor) are shown to exert a cooperative effect in inducing cell differentiation. Data suggest that the appearance of the factor determines the moment amoebae become responsive to cyclic AMP pulses.", "contents": "A differentiation stimulating factor induces cell sensitivity to 3':5'-cyclic AMP pulses in dictyostelium discoideum. During the first few hours of starvation, Dictyostelium discoideum amoebae excrete a macromolecule, probably a glycoprotein, which stimulates cell differentiation to aggregation competence. 3':5'-Cyclic AMP pulses, which mimic the chemotactic signal, and this factor (differentiation stimulating factor) are shown to exert a cooperative effect in inducing cell differentiation. Data suggest that the appearance of the factor determines the moment amoebae become responsive to cyclic AMP pulses."} {"id": "PMID:177983", "title": "Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in oxygen-enriched environment: preliminary report.", "content": "Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate in an incubator containing 95% air, 5% CO2. In an incubator atmosphere enriched with oxygen, however, the normal fibroblasts are maintained without proliferation, while the Rous sarcoma virus-infected fibroblasts continue to proliferate. This suggests that a respiratory function may be involved in the regulation of proliferation of normal cells, and that neoplastic cells may proliferate autonomously because of a deficiency in this regulatory function.", "contents": "Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in oxygen-enriched environment: preliminary report. Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate in an incubator containing 95% air, 5% CO2. In an incubator atmosphere enriched with oxygen, however, the normal fibroblasts are maintained without proliferation, while the Rous sarcoma virus-infected fibroblasts continue to proliferate. This suggests that a respiratory function may be involved in the regulation of proliferation of normal cells, and that neoplastic cells may proliferate autonomously because of a deficiency in this regulatory function."} {"id": "PMID:177984", "title": "Cotransfer of two linked human genes into cultured mouse cells.", "content": "Two linked human genes which code for the expression of cytosol thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred via purified metaphase chromosomes from the human lymphoblastoid cell line WI-L2a, into mouse L-cells [B82 and LM(TK-)]. Both genes have previously been shown to be closely linked on the human chromosome E17, band q21-22. Coexpression of both human enzyme markers was detected in two out of eight gene transfer clones, whilst the remaining six clones contained only human cytosol thymidine kinase, as shown by electrophoretic techniques. A further 23 human enzyme markers corresponding to 15 different human chromosomes were found to be absent in these gene transfer clones. No human chromosome or chromosomal fragment could be detected by karyotype analyses. Some of the gene transfer clones rapidly lost the transferred donor material when grown in nonselective medium, whereas others expressed a stable phenotype under these conditions. Prolonged maintenance in selective medium favors the survival of gene transfer cells expressing a stable phenotype. Possibly these cells harbor the donor genes integrated into a recipient chromosome.", "contents": "Cotransfer of two linked human genes into cultured mouse cells. Two linked human genes which code for the expression of cytosol thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred via purified metaphase chromosomes from the human lymphoblastoid cell line WI-L2a, into mouse L-cells [B82 and LM(TK-)]. Both genes have previously been shown to be closely linked on the human chromosome E17, band q21-22. Coexpression of both human enzyme markers was detected in two out of eight gene transfer clones, whilst the remaining six clones contained only human cytosol thymidine kinase, as shown by electrophoretic techniques. A further 23 human enzyme markers corresponding to 15 different human chromosomes were found to be absent in these gene transfer clones. No human chromosome or chromosomal fragment could be detected by karyotype analyses. Some of the gene transfer clones rapidly lost the transferred donor material when grown in nonselective medium, whereas others expressed a stable phenotype under these conditions. Prolonged maintenance in selective medium favors the survival of gene transfer cells expressing a stable phenotype. Possibly these cells harbor the donor genes integrated into a recipient chromosome."} {"id": "PMID:177985", "title": "Human papilloma virus DNA: physical mapping and genetic heterogeneity.", "content": "The molecular weight of three preparations of human papilloma virus DNA derived from different plantar warts was determined by agarose gel electrophoresis or electron microscopic contour length measurement. It was found to amount to approximately 4.9 X 10(6). Analysis of this DNA after sequential digestion by four different restriction endonucleases (EcoRI, Bam, Hind II, and Hind III) permitted physical mapping of the cleavage sites. Two of the three DNA preparations revealed an identical cleavage pattern, whereas the third one contained two additional cleavage sites.", "contents": "Human papilloma virus DNA: physical mapping and genetic heterogeneity. The molecular weight of three preparations of human papilloma virus DNA derived from different plantar warts was determined by agarose gel electrophoresis or electron microscopic contour length measurement. It was found to amount to approximately 4.9 X 10(6). Analysis of this DNA after sequential digestion by four different restriction endonucleases (EcoRI, Bam, Hind II, and Hind III) permitted physical mapping of the cleavage sites. Two of the three DNA preparations revealed an identical cleavage pattern, whereas the third one contained two additional cleavage sites."} {"id": "PMID:177987", "title": "Cyclic nucleotides, adenylate cyclase, and cyclic AMP phosphodiesterase in mammary glands from pregnant and lactating mice.", "content": "In the mammary glands of mice, levels of cyclic AMP increased during pregnancy and then fell precipitously following parturition. In contrast, levels of cyclic GMP fell during the gestation period and then rose rapidly during the early days of lactation. Adenylate cyclase and cyclic AMP hohsphodiesterase activities were elevated during the pregnancy and lactation periods.", "contents": "Cyclic nucleotides, adenylate cyclase, and cyclic AMP phosphodiesterase in mammary glands from pregnant and lactating mice. In the mammary glands of mice, levels of cyclic AMP increased during pregnancy and then fell precipitously following parturition. In contrast, levels of cyclic GMP fell during the gestation period and then rose rapidly during the early days of lactation. Adenylate cyclase and cyclic AMP hohsphodiesterase activities were elevated during the pregnancy and lactation periods."} {"id": "PMID:177988", "title": "Detection of antibody to Varicella-Zoster virus by immune adherence hemagglutination.", "content": "A serologic test for measurement of antibody to V-Z virus by immune adherence hemagglutination is described. Initial evaluation of the test has shown it to be highly sensitive, specific, rapid, and simple to perform. The V-Z antigen may be stored at -70 degrees, and the test could be performed in any routine serology laboratory.", "contents": "Detection of antibody to Varicella-Zoster virus by immune adherence hemagglutination. A serologic test for measurement of antibody to V-Z virus by immune adherence hemagglutination is described. Initial evaluation of the test has shown it to be highly sensitive, specific, rapid, and simple to perform. The V-Z antigen may be stored at -70 degrees, and the test could be performed in any routine serology laboratory."} {"id": "PMID:177990", "title": "Epiphyseal cartilage cyclic nucleotide phosphodiesterase: partial purification and kinetic characteristics of multiple enzymes.", "content": "Partial purification of chicken epiphyseal PDE activity by centrifugation and column chromatography has defined two distinct peaks of PDE activity. The faster eluting peak (I) has a higher apparent Km for cyclic AMP than the slower eluting major peak (IIs and II). Peak I has greater activity towards cyclic AMP as a substrate than towards cyclic GMP but does use both substrates. Peak I is not inhibited by T-3 or indomethacin at physiological concentrations. Substrates studies demonstrate the presence of at least two overlapping PDE species in the major peak(IIs and II). There is suggestive evidence that indomethacin is a more potent inhibitor of peak IIs which can use either cyclic AMP or cyclic GMP as substrates, whereas T-3 is a more potent inhibitor of fractions eluting where the enzyme only has activity with cyclic AMP.", "contents": "Epiphyseal cartilage cyclic nucleotide phosphodiesterase: partial purification and kinetic characteristics of multiple enzymes. Partial purification of chicken epiphyseal PDE activity by centrifugation and column chromatography has defined two distinct peaks of PDE activity. The faster eluting peak (I) has a higher apparent Km for cyclic AMP than the slower eluting major peak (IIs and II). Peak I has greater activity towards cyclic AMP as a substrate than towards cyclic GMP but does use both substrates. Peak I is not inhibited by T-3 or indomethacin at physiological concentrations. Substrates studies demonstrate the presence of at least two overlapping PDE species in the major peak(IIs and II). There is suggestive evidence that indomethacin is a more potent inhibitor of peak IIs which can use either cyclic AMP or cyclic GMP as substrates, whereas T-3 is a more potent inhibitor of fractions eluting where the enzyme only has activity with cyclic AMP."} {"id": "PMID:177991", "title": "Serologic response to BK Virus following human infection with SV40.", "content": "A small group of human volunteers given live SV40 virus, and who sero-converted to SV40, did not develop any heterologous antibody response to BK virus, even when BK antibody was demonstrated in preinfection sera. SV40 infection does not appear to contribute significantly to the patterns of BK antibody seen in human populations.", "contents": "Serologic response to BK Virus following human infection with SV40. A small group of human volunteers given live SV40 virus, and who sero-converted to SV40, did not develop any heterologous antibody response to BK virus, even when BK antibody was demonstrated in preinfection sera. SV40 infection does not appear to contribute significantly to the patterns of BK antibody seen in human populations."} {"id": "PMID:177992", "title": "Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection.", "content": "Since age-dependent diminished macrophage function has been related to the increased susceptibility of newborn mice to herpes simplex virus (HSV) infection, the effect of several agents which might activate macrophages or other cells involved in immunity was investigated. BCG, typhoid vaccine, brucella vaccine, levamisole, or staphage lysate were administered to newborn mice prior to challenge with HSV-2. Of these agents, only BCG, administered ip or id 6 days prior to challenge, was found to increase the survival rate of newborn mice. The possible use of BCG, alone or in combination with other modalities, for the prevention or treatment of neonatal HSV infections is discussed.", "contents": "Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Since age-dependent diminished macrophage function has been related to the increased susceptibility of newborn mice to herpes simplex virus (HSV) infection, the effect of several agents which might activate macrophages or other cells involved in immunity was investigated. BCG, typhoid vaccine, brucella vaccine, levamisole, or staphage lysate were administered to newborn mice prior to challenge with HSV-2. Of these agents, only BCG, administered ip or id 6 days prior to challenge, was found to increase the survival rate of newborn mice. The possible use of BCG, alone or in combination with other modalities, for the prevention or treatment of neonatal HSV infections is discussed."} {"id": "PMID:177993", "title": "Early events in the lytic infection of primary mouse kidney cell culture with polyoma virus. The effect of various input multiplicities.", "content": "Early polyoma (Py) virus-specific RNA synthesis was examined in cells infected with different concentrations of Py-virus. The effect of various multiplicities of infection (m.o.i.) on the rate of Py-RNA synthesis is different at 30 hr as compared to 65 hr. Thirty hours after infection at 27degrees, in the presence of 5-fluoro-2-deoxyuridine (FdU), an increase in input multiplicity was not associated with a quantitatively commensurate increase in the amount of virus-specific RNA synthesized. At 65 hr, the amount of viral RNA synthesized was roughly proportional to the number of infecting virus particles.", "contents": "Early events in the lytic infection of primary mouse kidney cell culture with polyoma virus. The effect of various input multiplicities. Early polyoma (Py) virus-specific RNA synthesis was examined in cells infected with different concentrations of Py-virus. The effect of various multiplicities of infection (m.o.i.) on the rate of Py-RNA synthesis is different at 30 hr as compared to 65 hr. Thirty hours after infection at 27degrees, in the presence of 5-fluoro-2-deoxyuridine (FdU), an increase in input multiplicity was not associated with a quantitatively commensurate increase in the amount of virus-specific RNA synthesized. At 65 hr, the amount of viral RNA synthesized was roughly proportional to the number of infecting virus particles."} {"id": "PMID:177994", "title": "Hepatic carbamyl phosphate synthetase and ornithine transcarbamylase in mouse influenze A and influenze B infection.", "content": "In mice infected with mouse-adapted influenza A/PR/8/34, hepatic carbamyl phosphate synthetase (CPS) activity was reduced to 88%, and ornithine transcarbamylase (OTC) was reduced to 83% of control values. In mice infected with mouse-adapted B/Lee/40, CPS activity was 98% was 94% of control values. These limited reductions in enzyme activity were attributed to a nonspecific debilitating effect of acute influenzal pneumonia. These findings suggest that the pronounced reduction of CPS and OTC activities reported in Reye's syndrome in man are not a general manifestation of the severity of influenza infection.", "contents": "Hepatic carbamyl phosphate synthetase and ornithine transcarbamylase in mouse influenze A and influenze B infection. In mice infected with mouse-adapted influenza A/PR/8/34, hepatic carbamyl phosphate synthetase (CPS) activity was reduced to 88%, and ornithine transcarbamylase (OTC) was reduced to 83% of control values. In mice infected with mouse-adapted B/Lee/40, CPS activity was 98% was 94% of control values. These limited reductions in enzyme activity were attributed to a nonspecific debilitating effect of acute influenzal pneumonia. These findings suggest that the pronounced reduction of CPS and OTC activities reported in Reye's syndrome in man are not a general manifestation of the severity of influenza infection."} {"id": "PMID:177997", "title": "Cyclic AMP and central noradrenaline receptors: failure to activate diencephalic adrenergic feeding pathways.", "content": "Intracranial injection of graded doses of dibutyryl 3',5'-cyclic adenosine monophosphoric acid (cAMP) at sites in the accumbens/stria terminalis nuclei of satiated rats elicited behavioural arousal and occasional convulsive episodes at higher doses, but failed to affect food consumption even in sites where injection of noradrenaline (65 nmol) consistently elicited increased feeding. Intracranial aminophylline (550 nmol) or dopamine (65 nmol) were also without effect on food consumption. This result does not support recent suggestions that cAMP serves as the second messenger in central noradrenergic motivational pathways.", "contents": "Cyclic AMP and central noradrenaline receptors: failure to activate diencephalic adrenergic feeding pathways. Intracranial injection of graded doses of dibutyryl 3',5'-cyclic adenosine monophosphoric acid (cAMP) at sites in the accumbens/stria terminalis nuclei of satiated rats elicited behavioural arousal and occasional convulsive episodes at higher doses, but failed to affect food consumption even in sites where injection of noradrenaline (65 nmol) consistently elicited increased feeding. Intracranial aminophylline (550 nmol) or dopamine (65 nmol) were also without effect on food consumption. This result does not support recent suggestions that cAMP serves as the second messenger in central noradrenergic motivational pathways."} {"id": "PMID:177995", "title": "Spontaneous behavior and sleep-wakefulness cycle in isolated and paired REM sleep deprived-marihuana treated rats.", "content": "The correlation between marihuana-induced aggressive behavior and changes in the sleep-wakefulness cycle was studied in chronically implanted rats. Marihuana injection in non-REM deprived rats did not induce aggressiveness irrespective of the animals being caged in isolation or paired. During this procedure quantization of the sleep-awake cycle revealed that wakefulness was increased while slow wave and REM sleep were decreased, mainly in the paired animals. REM deprived-marihuana injected animals recorded in isolation behaved like the control solution-injected rats. They showed a large rebound of REM and were not aggressive at the end of the 8 hr sessions. Conversely, when these animals were paired during the recording periods, they remained continuously awake and showed numerous episodes of aggressiveness. These results suggest that the aggressiveness inducing properties of marihuana are related to the REM deprivation and to the increased environmental stimulation achieved by pairing the animals.", "contents": "Spontaneous behavior and sleep-wakefulness cycle in isolated and paired REM sleep deprived-marihuana treated rats. The correlation between marihuana-induced aggressive behavior and changes in the sleep-wakefulness cycle was studied in chronically implanted rats. Marihuana injection in non-REM deprived rats did not induce aggressiveness irrespective of the animals being caged in isolation or paired. During this procedure quantization of the sleep-awake cycle revealed that wakefulness was increased while slow wave and REM sleep were decreased, mainly in the paired animals. REM deprived-marihuana injected animals recorded in isolation behaved like the control solution-injected rats. They showed a large rebound of REM and were not aggressive at the end of the 8 hr sessions. Conversely, when these animals were paired during the recording periods, they remained continuously awake and showed numerous episodes of aggressiveness. These results suggest that the aggressiveness inducing properties of marihuana are related to the REM deprivation and to the increased environmental stimulation achieved by pairing the animals."} {"id": "PMID:177996", "title": "Cephalic angiotensin receptors mediating drinking to systemic angiotensin II.", "content": "In rats implanted with cannulae to allow delivery of solutions to the cerebral ventricular system, pretreatment with 5 mug or 0.5 mug of saralasin acetate (Sar1 Ala8 Angiotensin II), an angiotensin II competitive analog, significantly attenuated drinking to subcutaneous (SC) injections of 500 mug of angiotensin II. However, pretreatment with either SC (5 mug or 20 mug) or with intravenous (5 mug) saralasin had no effect on drinking to SC angiotensin II (500 mug). Intracranial (IC) injections of 5 mug of saralasin had no effect on drinking in response to SC injections of 0.8 cc of a 10 percent NaCl solution and did not attenuate ingestion of a milk solution in a dessert test. On the basis of the specificity and the greater efficacy shown by IC saralasin in attenuating drinking to systemically applied angiotensin II, it was concluded that circulating angiotensin II reaches brain periventricular receptors which mediate drinking.", "contents": "Cephalic angiotensin receptors mediating drinking to systemic angiotensin II. In rats implanted with cannulae to allow delivery of solutions to the cerebral ventricular system, pretreatment with 5 mug or 0.5 mug of saralasin acetate (Sar1 Ala8 Angiotensin II), an angiotensin II competitive analog, significantly attenuated drinking to subcutaneous (SC) injections of 500 mug of angiotensin II. However, pretreatment with either SC (5 mug or 20 mug) or with intravenous (5 mug) saralasin had no effect on drinking to SC angiotensin II (500 mug). Intracranial (IC) injections of 5 mug of saralasin had no effect on drinking in response to SC injections of 0.8 cc of a 10 percent NaCl solution and did not attenuate ingestion of a milk solution in a dessert test. On the basis of the specificity and the greater efficacy shown by IC saralasin in attenuating drinking to systemically applied angiotensin II, it was concluded that circulating angiotensin II reaches brain periventricular receptors which mediate drinking."} {"id": "PMID:178010", "title": "Hydroxyamino compounds produced by the oxidation of diamines with diamine oxidase in the presence of alcohol dehydrogenase.", "content": "When the diamines putrescine, cadaverine, cystamine and lanthionamine are oxidized by purified pig kidney diamine oxidase in the presence of NADH and either liver or yeast crystalline alcohol dehydrogenase, NADH is oxidized. Chromatographic evidence obtained in the case of putrescine and cystamine indicates the production of the respective hydroxy-amino compound. In the case of cystamine, the product of the reaction is mercapto-ethanol-cysteamine mixed disulfide which may represent a biological source for the production of mercaptoethanol used for other reactions.", "contents": "Hydroxyamino compounds produced by the oxidation of diamines with diamine oxidase in the presence of alcohol dehydrogenase. When the diamines putrescine, cadaverine, cystamine and lanthionamine are oxidized by purified pig kidney diamine oxidase in the presence of NADH and either liver or yeast crystalline alcohol dehydrogenase, NADH is oxidized. Chromatographic evidence obtained in the case of putrescine and cystamine indicates the production of the respective hydroxy-amino compound. In the case of cystamine, the product of the reaction is mercapto-ethanol-cysteamine mixed disulfide which may represent a biological source for the production of mercaptoethanol used for other reactions."} {"id": "PMID:178011", "title": "The influence of denervation of the maturation of the flight muscle of Periplaneta americana.", "content": "The metathoracic musculature of the American cockroach Periplaneta americana was denervated by dissecting the nerves originating in the metathoracic ganglion on one side within 2 days after the last moult. The biochemical and morphological differences between normal and denervated musculature were followed two weeks later. Denervation completely prevents the gain in weight, protein content and cytochrome oxidase activity which occur in normal muscles during the two weeks after previous moulting. The content of phosphoarginine in the denervated muscle does not differ from the control muscle and is lower than in young muscles. The ability to resynthesize phosphoarginine postanaerobically is substantially lower in the denervated muscle than in control muscles, or in young muscles immediately after the last moult. The ultramicroscopic structure of the denervated muscle differs from that of the normal muscle: the mitochondria possess less cristae, the matrix between them appears less dense and the sarcoplasmatic reticulum is less developed. Thus the denervated muscle not only fails to mature, but also developes serious structural and biochemical disorders.", "contents": "The influence of denervation of the maturation of the flight muscle of Periplaneta americana. The metathoracic musculature of the American cockroach Periplaneta americana was denervated by dissecting the nerves originating in the metathoracic ganglion on one side within 2 days after the last moult. The biochemical and morphological differences between normal and denervated musculature were followed two weeks later. Denervation completely prevents the gain in weight, protein content and cytochrome oxidase activity which occur in normal muscles during the two weeks after previous moulting. The content of phosphoarginine in the denervated muscle does not differ from the control muscle and is lower than in young muscles. The ability to resynthesize phosphoarginine postanaerobically is substantially lower in the denervated muscle than in control muscles, or in young muscles immediately after the last moult. The ultramicroscopic structure of the denervated muscle differs from that of the normal muscle: the mitochondria possess less cristae, the matrix between them appears less dense and the sarcoplasmatic reticulum is less developed. Thus the denervated muscle not only fails to mature, but also developes serious structural and biochemical disorders."} {"id": "PMID:178012", "title": "Effect of diazepam on the electroencephalographic pattern and vigilance of unanaesthetized and curarized rats with a chronic cobalt-gelatin focus.", "content": "The author studied the effect of diazepam in doses of 1 and 3 mg/kg on rats with a chronic cortical cobalt-gelatin focus and implanted cortical and subcortical electrodes. Focal spike activity localized at the site of the focus and hypersynchronous generalized episodes of spikes (and waves) of 8--9/sec frequency were studied in the electroencephalogram and the main phases of vigilance (waking, telencephalic slow waves/SWS/and REM sleep) after diazepam were evaluated. The effect of diazepam on rats temporarily immobilized with tubocurarine was also evaluated. 1. Focal spike activity during sleep was mildly inhibited by diazepam. If present in the waking state, it was markedly inhibited. 2. The number of episodes diminished significantly after diazepam. The maximum decrease occurred 30--45 minutes after administering diazepam and after that they slowly recovered. 3. Diazepam did not inhibit alteration of the phases of vigilance, but there was an increase in the proportion of telencephalic sleep with large numbers of spidles of 12--14/sec frequency and the incidence of REM phases rose by 250--300%. 4. Diazepam brought no renewal of the episodes which disappeared from the waking EEG recording of rats with a chronic focus temporarily immobilized with tubocurarine. Its administration was followed mostly by sleep activity with spindles. 5. Despite certain effects in common (disappearance of episodes), the action of diazepam differs from that of barbiturates in many respects and is effected by different mechanisms.", "contents": "Effect of diazepam on the electroencephalographic pattern and vigilance of unanaesthetized and curarized rats with a chronic cobalt-gelatin focus. The author studied the effect of diazepam in doses of 1 and 3 mg/kg on rats with a chronic cortical cobalt-gelatin focus and implanted cortical and subcortical electrodes. Focal spike activity localized at the site of the focus and hypersynchronous generalized episodes of spikes (and waves) of 8--9/sec frequency were studied in the electroencephalogram and the main phases of vigilance (waking, telencephalic slow waves/SWS/and REM sleep) after diazepam were evaluated. The effect of diazepam on rats temporarily immobilized with tubocurarine was also evaluated. 1. Focal spike activity during sleep was mildly inhibited by diazepam. If present in the waking state, it was markedly inhibited. 2. The number of episodes diminished significantly after diazepam. The maximum decrease occurred 30--45 minutes after administering diazepam and after that they slowly recovered. 3. Diazepam did not inhibit alteration of the phases of vigilance, but there was an increase in the proportion of telencephalic sleep with large numbers of spidles of 12--14/sec frequency and the incidence of REM phases rose by 250--300%. 4. Diazepam brought no renewal of the episodes which disappeared from the waking EEG recording of rats with a chronic focus temporarily immobilized with tubocurarine. Its administration was followed mostly by sleep activity with spindles. 5. Despite certain effects in common (disappearance of episodes), the action of diazepam differs from that of barbiturates in many respects and is effected by different mechanisms."} {"id": "PMID:178013", "title": "Effect of adrenal glucocorticoids on beta-lipoprotein production by resected liver.", "content": "The action of adrenal glucocorticoids on the level of liver beta-lipoprotein (LP) production was studied. Their effect was verified by studying LP synthesis and release from liver after the administration of various doses of glucocorticoids, after the administration of ACTH and in cases in which the effect of glucocorticoids was precluded by adrenalectomy (in vivo and in vitro). Adrenal glucocorticoids were found to limit triglyceride release in the form of beta-LP from the liver into the blood stream during the first 6 hours after partial hepatectomy (PHE). A direct study of beta-LP synthesis in the liver tissue showed that glucocorticoids inhibit liver lipid secretion by interfering with the process of beta-LP release by the liver rather than by influencing actual beta-LP synthesis in the liver.", "contents": "Effect of adrenal glucocorticoids on beta-lipoprotein production by resected liver. The action of adrenal glucocorticoids on the level of liver beta-lipoprotein (LP) production was studied. Their effect was verified by studying LP synthesis and release from liver after the administration of various doses of glucocorticoids, after the administration of ACTH and in cases in which the effect of glucocorticoids was precluded by adrenalectomy (in vivo and in vitro). Adrenal glucocorticoids were found to limit triglyceride release in the form of beta-LP from the liver into the blood stream during the first 6 hours after partial hepatectomy (PHE). A direct study of beta-LP synthesis in the liver tissue showed that glucocorticoids inhibit liver lipid secretion by interfering with the process of beta-LP release by the liver rather than by influencing actual beta-LP synthesis in the liver."} {"id": "PMID:178014", "title": "Pregnancy interrupting effects of some bacterial toxins.", "content": "Embryotoxic properties of Shigella dysenteriae and Clostridium perfringens toxins, of E. coli endotoxin, V. cholerase and E. coli enterotoxins were compared in mice. E. coli endotoxin has embryotoxic effects at all stages of pregnancy. E. coli enterotoxin V. cholerae enterotoxin and Shigella dysenteriae toxin are most effective mainly at earlier stages of pregnancy. Clostridium perfringens toxin has no embryotoxic effect.", "contents": "Pregnancy interrupting effects of some bacterial toxins. Embryotoxic properties of Shigella dysenteriae and Clostridium perfringens toxins, of E. coli endotoxin, V. cholerase and E. coli enterotoxins were compared in mice. E. coli endotoxin has embryotoxic effects at all stages of pregnancy. E. coli enterotoxin V. cholerae enterotoxin and Shigella dysenteriae toxin are most effective mainly at earlier stages of pregnancy. Clostridium perfringens toxin has no embryotoxic effect."} {"id": "PMID:178015", "title": "Remediable neuromuscular disorders.", "content": "Generalized muscular weakness may develop from a variety of causes, and in many cases is reversible with appropriate treatment of the underlying disorder.", "contents": "Remediable neuromuscular disorders. Generalized muscular weakness may develop from a variety of causes, and in many cases is reversible with appropriate treatment of the underlying disorder."} {"id": "PMID:178016", "title": "[Aspects of the value of humoral antibodies in encephalomyelitis of neuroallergic origin].", "content": "The importance of humoral antibodies formed in the course of neuroallergic diseases characterized by a cytergic type of reaction and especially in the course of experimental allergic encephalomyelitis (EAEM) is discussed, special attention being given to the importance of pathogenetic, immunodynamic, diagnostic, and therapeutic factors. The circulating antibodies of EAEM induced by cellular and humoral immunoprocesses are assumed to produce either intensifying or mitigating effects. Among the most important functions are the influence of immune globulins on the blood/brain boundary lesion, the gliotoxic and myelinotoxic effects, and the detection of a blockade of the intraneural transmission. The therapeutical effect to be discussed in the light of the protective effects of humoral antibodies is a mere conception in view of incompletely understood mechanisms including those governing the chronology and dynamics of immunoprocesses associated with multiple sclerosis, especially since the antigen-specific induction of tolerance appears to be far more essential.", "contents": "[Aspects of the value of humoral antibodies in encephalomyelitis of neuroallergic origin]. The importance of humoral antibodies formed in the course of neuroallergic diseases characterized by a cytergic type of reaction and especially in the course of experimental allergic encephalomyelitis (EAEM) is discussed, special attention being given to the importance of pathogenetic, immunodynamic, diagnostic, and therapeutic factors. The circulating antibodies of EAEM induced by cellular and humoral immunoprocesses are assumed to produce either intensifying or mitigating effects. Among the most important functions are the influence of immune globulins on the blood/brain boundary lesion, the gliotoxic and myelinotoxic effects, and the detection of a blockade of the intraneural transmission. The therapeutical effect to be discussed in the light of the protective effects of humoral antibodies is a mere conception in view of incompletely understood mechanisms including those governing the chronology and dynamics of immunoprocesses associated with multiple sclerosis, especially since the antigen-specific induction of tolerance appears to be far more essential."} {"id": "PMID:178017", "title": "The continuing care clinic: outpatient treatment of the chronically ill.", "content": "The need for continuing care of chronic psychiatric patients within the community is a pressing problem that calls for development and testing of new treatment methods. This paper describes one such method, the Continuing Care Clinic, an outpatient program for chronic patients who have not responded well to other outpatient treatment approaches. The clinic's structure, treatment rationale and procedures, and clinical results over a 31/2-year period are described. Among specific treatment features discussed are the use of multiple therapists, focus on available personality strengths and on reality issues, and patient-staff group interaction as an adjunct to individual psychotherapy.", "contents": "The continuing care clinic: outpatient treatment of the chronically ill. The need for continuing care of chronic psychiatric patients within the community is a pressing problem that calls for development and testing of new treatment methods. This paper describes one such method, the Continuing Care Clinic, an outpatient program for chronic patients who have not responded well to other outpatient treatment approaches. The clinic's structure, treatment rationale and procedures, and clinical results over a 31/2-year period are described. Among specific treatment features discussed are the use of multiple therapists, focus on available personality strengths and on reality issues, and patient-staff group interaction as an adjunct to individual psychotherapy."} {"id": "PMID:178021", "title": "[Functional diencephalo-pituitary diagnosis by means of radioimmunoassay].", "content": "The Author, after mentionating the always increasing need of cooperation between the clinical activity and the laboratory research, stops considering the semeiological meaning of the radioimmunoassay of the pituitary hormones. However he worns against the limitations that such dosages present at the base line and the possible dissociation between immunological activity and biological activity. He describes then the dynamic tests able to determine variations of hormonal levels and makes his conclusions stating that the observation made during dynamic conditions may be of help to the clinical diagnosis.", "contents": "[Functional diencephalo-pituitary diagnosis by means of radioimmunoassay]. The Author, after mentionating the always increasing need of cooperation between the clinical activity and the laboratory research, stops considering the semeiological meaning of the radioimmunoassay of the pituitary hormones. However he worns against the limitations that such dosages present at the base line and the possible dissociation between immunological activity and biological activity. He describes then the dynamic tests able to determine variations of hormonal levels and makes his conclusions stating that the observation made during dynamic conditions may be of help to the clinical diagnosis."} {"id": "PMID:178022", "title": "[Technical notes and clinical use of radioimmunologic determination of plasma ACTH].", "content": "Particular aspects of plasma ACTH radioimmunoassay are examinated. The results obtained with this method in adrenocortical diseases (Addison's disease, Cushing's syndrome, congenital adrenal hyperplasia) are reported and clinical value in etiological diagnosis of Cushing's syndrome is outlined. Moreover the results obtained in other syndromes of endocrinologic interest (massive obesity, Turner's and Klinefelter's syndromes, Laurence-Moon-Biedl syndrome, true precocious puberty, primary hypothyroidism, hypopituitary dwarphism) are reported and discussed.", "contents": "[Technical notes and clinical use of radioimmunologic determination of plasma ACTH]. Particular aspects of plasma ACTH radioimmunoassay are examinated. The results obtained with this method in adrenocortical diseases (Addison's disease, Cushing's syndrome, congenital adrenal hyperplasia) are reported and clinical value in etiological diagnosis of Cushing's syndrome is outlined. Moreover the results obtained in other syndromes of endocrinologic interest (massive obesity, Turner's and Klinefelter's syndromes, Laurence-Moon-Biedl syndrome, true precocious puberty, primary hypothyroidism, hypopituitary dwarphism) are reported and discussed."} {"id": "PMID:178024", "title": "Gray scale ultrasonic investigation of focal defects on 99Tc sulphur colloid liver scanning.", "content": "Radionuclide liver scanning, though a well established technique for the detection of normal liver tissue replacement, has yet to deliver a satisfactory isotope method for distinguishing the benign or malignant nature of a disclosed nonfunctioning area. The solid or cystic nature of focal areas of replacement can be shown by ultrasonic echography, so the malignancy of the area can be inferred. The complementary use of both techniques is recommended.", "contents": "Gray scale ultrasonic investigation of focal defects on 99Tc sulphur colloid liver scanning. Radionuclide liver scanning, though a well established technique for the detection of normal liver tissue replacement, has yet to deliver a satisfactory isotope method for distinguishing the benign or malignant nature of a disclosed nonfunctioning area. The solid or cystic nature of focal areas of replacement can be shown by ultrasonic echography, so the malignancy of the area can be inferred. The complementary use of both techniques is recommended."} {"id": "PMID:178025", "title": "The effect of steroids on the extravascular distribution of radiographic contrast material and technetium pertechnetate in brain tumors as determined by computed tomography.", "content": "The effect of dexamethasone on the accumulation of iothalamate and 99mTc pertechnetate in cerebral tumors was investigated in 6 patients over a five-month period. Patients were examined by x-ray (transmission) computed tomography (CT) and by radionuclide (emission) computed tomography (RCT) prior to and during a course of dexamethasone therapy. Stenosis diminished the degree of accumulation of both agents but did not change the boundaries of their distribution.", "contents": "The effect of steroids on the extravascular distribution of radiographic contrast material and technetium pertechnetate in brain tumors as determined by computed tomography. The effect of dexamethasone on the accumulation of iothalamate and 99mTc pertechnetate in cerebral tumors was investigated in 6 patients over a five-month period. Patients were examined by x-ray (transmission) computed tomography (CT) and by radionuclide (emission) computed tomography (RCT) prior to and during a course of dexamethasone therapy. Stenosis diminished the degree of accumulation of both agents but did not change the boundaries of their distribution."} {"id": "PMID:178028", "title": "Studies of growth hormone secretion VIII. Effects of alpha,beta-methylene-ATP on prostglandin induced GH release and cyclic AMP accumlation in rat anterior pituitary glands.", "content": "Alpha, beta-methylene-ATP, a competitive inhibitor of adenylate cyclase of liver and fat cell membrane preparations, caused a dose related inhibition of PGE1 and PGE2-induced cyclic AMP accumulation in rat anterior pituitary explants. At the same time, this ATP analog potentiated PGE1 and PGE2-promoted growth hormone secretion. The possible functional role of prostaglandins and cyclic nucleotides in the regulation of growth hormone secretion remains to be defined.", "contents": "Studies of growth hormone secretion VIII. Effects of alpha,beta-methylene-ATP on prostglandin induced GH release and cyclic AMP accumlation in rat anterior pituitary glands. Alpha, beta-methylene-ATP, a competitive inhibitor of adenylate cyclase of liver and fat cell membrane preparations, caused a dose related inhibition of PGE1 and PGE2-induced cyclic AMP accumulation in rat anterior pituitary explants. At the same time, this ATP analog potentiated PGE1 and PGE2-promoted growth hormone secretion. The possible functional role of prostaglandins and cyclic nucleotides in the regulation of growth hormone secretion remains to be defined."} {"id": "PMID:178029", "title": "Hypothalamic and pituitary effects of prostaglandins on ACTH secretion.", "content": "Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF.", "contents": "Hypothalamic and pituitary effects of prostaglandins on ACTH secretion. Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF."} {"id": "PMID:178031", "title": "Spectral changes in the respiratory chain of cerebral cortex slices. Correlation with the energy status of the tissue.", "content": "Elevation of the media potassium concentration results in an immediate, but transient increase in the rate of respiration in cerebral cortex slices of the rat. As the respiratory burst decrease in intensity, a transient oxidation of the tissue respiratory intermediates is followed by a net reduction. The burst of respiration is accompanied by a large decrease in tissue ATP and phosphocreatine concentrations. ATP and phosphocreatine concentrations are essentially fully recovered within 5-6 min. The apparent increase in ATP hydrolysis during the peak of the respiratory response was not, however, accompanied by increases in the tissue content of ADP and 5'-AMP. Increased deamination of the adenine nucleotides is discussed as a possible mechanism in the large contraction of the total adenine pool observed during the course of the metabolic response to elevated potassium concentrations.", "contents": "Spectral changes in the respiratory chain of cerebral cortex slices. Correlation with the energy status of the tissue. Elevation of the media potassium concentration results in an immediate, but transient increase in the rate of respiration in cerebral cortex slices of the rat. As the respiratory burst decrease in intensity, a transient oxidation of the tissue respiratory intermediates is followed by a net reduction. The burst of respiration is accompanied by a large decrease in tissue ATP and phosphocreatine concentrations. ATP and phosphocreatine concentrations are essentially fully recovered within 5-6 min. The apparent increase in ATP hydrolysis during the peak of the respiratory response was not, however, accompanied by increases in the tissue content of ADP and 5'-AMP. Increased deamination of the adenine nucleotides is discussed as a possible mechanism in the large contraction of the total adenine pool observed during the course of the metabolic response to elevated potassium concentrations."} {"id": "PMID:178032", "title": "Genetic determination of aggressive behavior and brain cyclic AMP.", "content": "Inbred mouse strains exhibit differences in brain cyclic AMP concentrations. In two mouse strains, we have shown that both the tendency for aggressive attack and high brain cyclic AMP content are inherited as recessive traits and that these traits maintain a close association in segregating generations.", "contents": "Genetic determination of aggressive behavior and brain cyclic AMP. Inbred mouse strains exhibit differences in brain cyclic AMP concentrations. In two mouse strains, we have shown that both the tendency for aggressive attack and high brain cyclic AMP content are inherited as recessive traits and that these traits maintain a close association in segregating generations."} {"id": "PMID:178033", "title": "17 alpha estradiol: separation of estrogen effect on collagen from other clinical and biochemical effects in man.", "content": "In rodents the effect of 17alpha estradiol upon collagen is identical to that of 17beta estradiol, but the 17alpha estradiol effect upon uterine lining is 1/1000 that of 17beta estradiol. Both steroids reverse the effect of D-penicillamine on rodent skin collagen. Five human beings with the skin collagen changes associated with D-penicillamine were treated with 17alpha estradiol for three to six weeks. 17alpha estradiol caused no detectable changes in blood pressure, breast development, menstrual periods, serum liver enzymes, serum proteins, plasma growth hormone, insulin, serum clotting factors, serum triglycerides, serum copper or serum ceruloplasma. In contrast, 17alpha estradiol increased skin prolyl hydroxylase activity, increased soluble collagen content in the skin and increased urinary hydroxyproline excretion. These studies with 17alpha estradiol, point out a specificity difference between the various sites of estrogen action in human beings.", "contents": "17 alpha estradiol: separation of estrogen effect on collagen from other clinical and biochemical effects in man. In rodents the effect of 17alpha estradiol upon collagen is identical to that of 17beta estradiol, but the 17alpha estradiol effect upon uterine lining is 1/1000 that of 17beta estradiol. Both steroids reverse the effect of D-penicillamine on rodent skin collagen. Five human beings with the skin collagen changes associated with D-penicillamine were treated with 17alpha estradiol for three to six weeks. 17alpha estradiol caused no detectable changes in blood pressure, breast development, menstrual periods, serum liver enzymes, serum proteins, plasma growth hormone, insulin, serum clotting factors, serum triglycerides, serum copper or serum ceruloplasma. In contrast, 17alpha estradiol increased skin prolyl hydroxylase activity, increased soluble collagen content in the skin and increased urinary hydroxyproline excretion. These studies with 17alpha estradiol, point out a specificity difference between the various sites of estrogen action in human beings."} {"id": "PMID:178034", "title": "Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate.", "content": "Androgenic deprivation resulted in marked impairment of prostate weight and significant alterations in cytosolic and particulate protein kinase activities and cyclic AMP-binding capacity of this tissue. Whereas rats orchidectomized for 7 days exhibited significant enhancement in the specific activity of cytosolic cyclic AMP-dependent (73%) and -independent (45%) protein kinases as well as cyclic AMP-binding protein (196%), administration of testosterone (5.0 mg/100 g, i.m., 5 days) exerted little or no effect in reversing these responses. In contrast, when expressed as total enzyme activity per prostate, castration led to marked decreases in protein kinase activity assayed in the presence (87%) and absence of the cyclic nucleotide (91%). Likewise, the cyclic AMP-binding capacity of the soluble enzyme was depressed (77%) following androgenic deprivation. Although testosterone treatment for 3 days significantly reversed these effects, complete restoration was not achieved even after 5 days of androgen replacement therapy. Moreover, while exogenous cyclic AMP had no effect on protein kinase activity from crude nuclear preparations, the phosphorylation of endogenous nuclear substrates was dependent on androgenic status of the animals. Whereas castration produced decreases in the specific and total activity of prostatic particulate protein kinase as well as the cyclic AMP-binding protein, testosterone replenishment was effective in abolishing these alterations seen in orchidectomized rats. Data from the present study provide additional support to the concept that changes in cyclic AMP-adenylate cyclase-protein kinase system play an important role in the overall mechanism(s) by which male sex steroids exert their diverse anabolic effects on male accessory sex tissues.", "contents": "Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate. Androgenic deprivation resulted in marked impairment of prostate weight and significant alterations in cytosolic and particulate protein kinase activities and cyclic AMP-binding capacity of this tissue. Whereas rats orchidectomized for 7 days exhibited significant enhancement in the specific activity of cytosolic cyclic AMP-dependent (73%) and -independent (45%) protein kinases as well as cyclic AMP-binding protein (196%), administration of testosterone (5.0 mg/100 g, i.m., 5 days) exerted little or no effect in reversing these responses. In contrast, when expressed as total enzyme activity per prostate, castration led to marked decreases in protein kinase activity assayed in the presence (87%) and absence of the cyclic nucleotide (91%). Likewise, the cyclic AMP-binding capacity of the soluble enzyme was depressed (77%) following androgenic deprivation. Although testosterone treatment for 3 days significantly reversed these effects, complete restoration was not achieved even after 5 days of androgen replacement therapy. Moreover, while exogenous cyclic AMP had no effect on protein kinase activity from crude nuclear preparations, the phosphorylation of endogenous nuclear substrates was dependent on androgenic status of the animals. Whereas castration produced decreases in the specific and total activity of prostatic particulate protein kinase as well as the cyclic AMP-binding protein, testosterone replenishment was effective in abolishing these alterations seen in orchidectomized rats. Data from the present study provide additional support to the concept that changes in cyclic AMP-adenylate cyclase-protein kinase system play an important role in the overall mechanism(s) by which male sex steroids exert their diverse anabolic effects on male accessory sex tissues."} {"id": "PMID:178035", "title": "Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease.", "content": "Pig sera were assayed for antibodies to swine vesicular disease virus by (a) the radial immuno-diffusion technique combined with autoradiography and (by serum neutralisation tests. The former was more sensitive and was used for initial screening of sera while the latter was used to obtain estimates of titres of positive sera. In a survey of 1759 sera collected at slaughterhouses there were 14 significant titres from a total of seven premises situated in localities where the disease had been known to occur, and it was concluded that this did not indicate wither widespread undetected disease or the occurence of inapparent infection in the pig population.", "contents": "Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease. Pig sera were assayed for antibodies to swine vesicular disease virus by (a) the radial immuno-diffusion technique combined with autoradiography and (by serum neutralisation tests. The former was more sensitive and was used for initial screening of sera while the latter was used to obtain estimates of titres of positive sera. In a survey of 1759 sera collected at slaughterhouses there were 14 significant titres from a total of seven premises situated in localities where the disease had been known to occur, and it was concluded that this did not indicate wither widespread undetected disease or the occurence of inapparent infection in the pig population."} {"id": "PMID:178036", "title": "The effect of enterotoxin of Clostridium welchii (perfringens) type A on fowls.", "content": "Lethal doses of enterotoxin of Clostridium welchii (perfringens) type A injected intravenously into young fowls caused immediate lassitude, with partial recovery, followed by death seven to 35 h after inoculation. Lesions found were ascites, hydropericardium, oedema of the muscles, hepatic congestion, urate deposits on the peritoneum and the pericardium, and intestinal hyperaemia. Sublethal doses produced no clinical signs or lesion. The LD50 of this enterotoxin was 74-84 mug/kg of body weight.", "contents": "The effect of enterotoxin of Clostridium welchii (perfringens) type A on fowls. Lethal doses of enterotoxin of Clostridium welchii (perfringens) type A injected intravenously into young fowls caused immediate lassitude, with partial recovery, followed by death seven to 35 h after inoculation. Lesions found were ascites, hydropericardium, oedema of the muscles, hepatic congestion, urate deposits on the peritoneum and the pericardium, and intestinal hyperaemia. Sublethal doses produced no clinical signs or lesion. The LD50 of this enterotoxin was 74-84 mug/kg of body weight."} {"id": "PMID:178042", "title": "[Familial amyloid neuropathy of Corino Andrade. Ultrastructural study of the peripheral nerve in 2 patients].", "content": "The authors describe two typical cases of Portuguese amyloid neuropathy in immigrants. One of the patients had been ill for only a short time while the other's condition had been developing over more than ten years. The first patient's neuropathy was characterized by a perforating ulcer of the foot and loss of sensation. The neurological disorder as well as the effect on general health were much more serious in the second patient. Neuro-muscular biopsy was carried out on each of these patients and revealed excessive endoneural amyloid and very severe lesions of nerve parenchyma mainly secondary to Wallerian degeneration. The results were compared with the few existing ultrastructural studies on the peripheral nerve in amyloid neuropathies.", "contents": "[Familial amyloid neuropathy of Corino Andrade. Ultrastructural study of the peripheral nerve in 2 patients]. The authors describe two typical cases of Portuguese amyloid neuropathy in immigrants. One of the patients had been ill for only a short time while the other's condition had been developing over more than ten years. The first patient's neuropathy was characterized by a perforating ulcer of the foot and loss of sensation. The neurological disorder as well as the effect on general health were much more serious in the second patient. Neuro-muscular biopsy was carried out on each of these patients and revealed excessive endoneural amyloid and very severe lesions of nerve parenchyma mainly secondary to Wallerian degeneration. The results were compared with the few existing ultrastructural studies on the peripheral nerve in amyloid neuropathies."} {"id": "PMID:178046", "title": "[Subcutaneous and tendinous nodules in scleroderma. Apropos of 4 anatomo-clinical cases].", "content": "The authors have observed 3 cases of pure scleroderma and one case of scleroderma in which tendinous or subcutaneous nodular structures were present. To the author's knowledge, such nodules have never been described previously in cases of scleroderma. Their site and their histology identifies them as \"rheumatoid\" nodules and at the same time provides other valuable information. Scleroderma is thus, together with rheumatoid polyarthritis and lupus erythematosus, one of the possible causes of nodule formation, and the authors put forward the hypothesis that these nodules might represent one of the first lesions of the Thibierge and Weissenbach syndrome.", "contents": "[Subcutaneous and tendinous nodules in scleroderma. Apropos of 4 anatomo-clinical cases]. The authors have observed 3 cases of pure scleroderma and one case of scleroderma in which tendinous or subcutaneous nodular structures were present. To the author's knowledge, such nodules have never been described previously in cases of scleroderma. Their site and their histology identifies them as \"rheumatoid\" nodules and at the same time provides other valuable information. Scleroderma is thus, together with rheumatoid polyarthritis and lupus erythematosus, one of the possible causes of nodule formation, and the authors put forward the hypothesis that these nodules might represent one of the first lesions of the Thibierge and Weissenbach syndrome."} {"id": "PMID:178047", "title": "Transfer factor treatment of patients with multuple sclerosis. I. Preliminary report of changes in immunological parameters.", "content": "In five patients with definite multiple sclerosis and lack of cell-mediated immunity to measles and parainfluenza virus antigens, various immunological parameters were studied before and during transfer factor treatment. The study showed that cell-mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors.", "contents": "Transfer factor treatment of patients with multuple sclerosis. I. Preliminary report of changes in immunological parameters. In five patients with definite multiple sclerosis and lack of cell-mediated immunity to measles and parainfluenza virus antigens, various immunological parameters were studied before and during transfer factor treatment. The study showed that cell-mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors."} {"id": "PMID:178048", "title": "Changes in the surface of virus-induced cells recognized by cytotoxic T cells. I. Minimal requirements for lysis of ectromelia-infected P-815 cells.", "content": "P-815 mastocytoma cells developed susceptibility to immune T-cell-mediated cytolysis shortly after infection by ectromelia virus. Intracellular viral replication and late protein synthesis seem to bu unnecessary events. Interference with early protein synthesis, however, inhibits the development of susceptibility to lysis. The important intracellular events necessary for subsequent cytolysis appear to occur within 1 hour of infection. Virus rendered non-infectious by ultraviolet irradiation but not by gamma irradiation is able to induce these changes. By determining the minimum and essential events of the infectious process which result in T-cell-mediated cytolysis, the task of establishing the molecular changes occurring in the target cell surface membrane necessary for immune T-cell recognition should be simplified.", "contents": "Changes in the surface of virus-induced cells recognized by cytotoxic T cells. I. Minimal requirements for lysis of ectromelia-infected P-815 cells. P-815 mastocytoma cells developed susceptibility to immune T-cell-mediated cytolysis shortly after infection by ectromelia virus. Intracellular viral replication and late protein synthesis seem to bu unnecessary events. Interference with early protein synthesis, however, inhibits the development of susceptibility to lysis. The important intracellular events necessary for subsequent cytolysis appear to occur within 1 hour of infection. Virus rendered non-infectious by ultraviolet irradiation but not by gamma irradiation is able to induce these changes. By determining the minimum and essential events of the infectious process which result in T-cell-mediated cytolysis, the task of establishing the molecular changes occurring in the target cell surface membrane necessary for immune T-cell recognition should be simplified."} {"id": "PMID:178045", "title": "Attempts to improve the early enzymatic diagnosis of coronary heart disease.", "content": "Based on the hypothesis that beta lipoproteins have the ability to trap certain enzymes, an attempt was made to release these enzymes from the eventual beta lipoprotein blockade, by subjecting the serum to different processings such as: freezing-thawing (3 times), ultrasonation or treatment with Triton X100 or sodium desoxycholate. After the first two procedures an increase of serum LDH and alkaline phosphatase activities was observed in about half the sera investigated (normal and pathologic). In few cases of coronary heart disease (two out of 60), LDH activity reached a clearly pathologic level.", "contents": "Attempts to improve the early enzymatic diagnosis of coronary heart disease. Based on the hypothesis that beta lipoproteins have the ability to trap certain enzymes, an attempt was made to release these enzymes from the eventual beta lipoprotein blockade, by subjecting the serum to different processings such as: freezing-thawing (3 times), ultrasonation or treatment with Triton X100 or sodium desoxycholate. After the first two procedures an increase of serum LDH and alkaline phosphatase activities was observed in about half the sera investigated (normal and pathologic). In few cases of coronary heart disease (two out of 60), LDH activity reached a clearly pathologic level."} {"id": "PMID:178049", "title": "A reovirus-like agent (rotavirus) in gastroenteritis of children. Virus detection and serological studies.", "content": "A reovirus-like agent (rotavirus) was detected in 26 children (44%) when fecal specimens from 59 children with acute gastroenteritis were examined by electron microscopy. No rotavirus was detected in the feces of 49 children with other diseases. Sera from the acute and the convalescent phase from 40 children with acute gastroenteritis and from 18 other patients were examined for antibodies against a bovine rotavirus by an indirect fluorescent antibody test. 26 of the patients with gastroenteritis (65%) developed antibodies during their disease, whereas none of the other patients showed a rise in antibody titre. The specimens were submitted to the laboratory from hospitalized children during the period January 1973 through March 1975. Most of the cases of rotavirus gastroenteritis occurred during late autumn and early winter among children between 0.5 and 3 years of age. It is concluded that electron microscopy is a sensitive diagnostic technique during the acute phase of the disease, and that the serological test with bovine rotavirus antigen served as a useful diagnostic tool.", "contents": "A reovirus-like agent (rotavirus) in gastroenteritis of children. Virus detection and serological studies. A reovirus-like agent (rotavirus) was detected in 26 children (44%) when fecal specimens from 59 children with acute gastroenteritis were examined by electron microscopy. No rotavirus was detected in the feces of 49 children with other diseases. Sera from the acute and the convalescent phase from 40 children with acute gastroenteritis and from 18 other patients were examined for antibodies against a bovine rotavirus by an indirect fluorescent antibody test. 26 of the patients with gastroenteritis (65%) developed antibodies during their disease, whereas none of the other patients showed a rise in antibody titre. The specimens were submitted to the laboratory from hospitalized children during the period January 1973 through March 1975. Most of the cases of rotavirus gastroenteritis occurred during late autumn and early winter among children between 0.5 and 3 years of age. It is concluded that electron microscopy is a sensitive diagnostic technique during the acute phase of the disease, and that the serological test with bovine rotavirus antigen served as a useful diagnostic tool."} {"id": "PMID:178050", "title": "Early diagnosis of virus-caused vesicular rashes by immunofluorescence on skin biopsies. I. Varicella, zoster and herpes simplex.", "content": "The use of immunofluorescence (IF) for the rapid identification of varicella-zoster (V-Z) and herpes simplex (HS) antigen in frozen sections of biopsies of early non-vesicular skin lesions was investigated. Direct IF, using fluorescein- isothiocyanate- conjugated immuoglobulin (FITC Ig) of paired human anti-V-Z sera and FITC-conjugated negative and positive anti-V-Z-monkey Ig, yielded specific fluorescence of virus antigen in all 14 varicella cases investigated and in 10/11 zoster cases. In contrast, indirect IF, using paired human anti-zoster sera and a sheep anti-human Ig FITC, was not satisfactorily specific, since staining with the anti-human Ig FITC alone also yielded fluorescence of infected cells in some cases. In 6/8 cases of HS infection, specific fluorescence of virus antigen was obtained by direct IF, using FITC-conjugated negative and positive guinea-pig anti-HS Ig. Because of the often predominant distribution of virus antigen to the corium and the skin appendages, punch biopsies are apparently better than scraped material, at least in the prevesicular stage.", "contents": "Early diagnosis of virus-caused vesicular rashes by immunofluorescence on skin biopsies. I. Varicella, zoster and herpes simplex. The use of immunofluorescence (IF) for the rapid identification of varicella-zoster (V-Z) and herpes simplex (HS) antigen in frozen sections of biopsies of early non-vesicular skin lesions was investigated. Direct IF, using fluorescein- isothiocyanate- conjugated immuoglobulin (FITC Ig) of paired human anti-V-Z sera and FITC-conjugated negative and positive anti-V-Z-monkey Ig, yielded specific fluorescence of virus antigen in all 14 varicella cases investigated and in 10/11 zoster cases. In contrast, indirect IF, using paired human anti-zoster sera and a sheep anti-human Ig FITC, was not satisfactorily specific, since staining with the anti-human Ig FITC alone also yielded fluorescence of infected cells in some cases. In 6/8 cases of HS infection, specific fluorescence of virus antigen was obtained by direct IF, using FITC-conjugated negative and positive guinea-pig anti-HS Ig. Because of the often predominant distribution of virus antigen to the corium and the skin appendages, punch biopsies are apparently better than scraped material, at least in the prevesicular stage."} {"id": "PMID:178051", "title": "An estimate of the course of herpes simplex virus encephalitis.", "content": "Serologic responses, physical findings, and survival were studied in 51 cases of proved (14 patients) or presumptive (37 patients) herpes simplex encephalitis occurring in North America between 1965 and 1972. On the basis of a statistical analysis of 16 serological parameters tested in both groups, presumptive cases are likely similar to definitive cases. Using this assumption, the following tentatives conclusions are possible. Complement-fixing antibodies may be more sensitive measures of rises in anti-herpes simplex virus antibodies than are conventional or complement-requiring neutralizing or passive hemagglutinating antibodies. Mortality in herpes simplex virus encephalitis may vary from 0 to 80% and may be predictable depending upon the occurrence of seizures, paralysis and coma. Coma seems to dictate the dour prognosis. When 51 cases of herpes simplex virus encephalitis reported in the literature by others between 1944 and 1972 were analyzed by this method, a comparably varied mortality was obtained. It did not appear that treatment with idoxuridine increased the likelihood of survival.", "contents": "An estimate of the course of herpes simplex virus encephalitis. Serologic responses, physical findings, and survival were studied in 51 cases of proved (14 patients) or presumptive (37 patients) herpes simplex encephalitis occurring in North America between 1965 and 1972. On the basis of a statistical analysis of 16 serological parameters tested in both groups, presumptive cases are likely similar to definitive cases. Using this assumption, the following tentatives conclusions are possible. Complement-fixing antibodies may be more sensitive measures of rises in anti-herpes simplex virus antibodies than are conventional or complement-requiring neutralizing or passive hemagglutinating antibodies. Mortality in herpes simplex virus encephalitis may vary from 0 to 80% and may be predictable depending upon the occurrence of seizures, paralysis and coma. Coma seems to dictate the dour prognosis. When 51 cases of herpes simplex virus encephalitis reported in the literature by others between 1944 and 1972 were analyzed by this method, a comparably varied mortality was obtained. It did not appear that treatment with idoxuridine increased the likelihood of survival."} {"id": "PMID:178053", "title": "Cholera toxin induces pineal enzymes in culture.", "content": "Addition of choleragen to rat pineal organ cultures caused a long-lasting stimulation of adenylate cyclase activity, and this was followed by increases in seroton N-acetyltransferase and cyclic adenosine monophosphate phosphodiesterase activities. These effects of choleragen were not blocked by the beta-adrenoceptor antagonist propranolol, but the increases in cyclic adenosine monophosphate phosphodiesterase and serotonin N-acetyltransferase activities could be prevented by the protein synthesis inhibitor cycloheximide. The results indicate that cholera toxin can mimic the induction of pineal enzymes that normally follows beta-adrenoceptor activation and suggest that increased cyclic adenosine monophosphate is a necessary and sufficient signal for such changes in enzyme activity.", "contents": "Cholera toxin induces pineal enzymes in culture. Addition of choleragen to rat pineal organ cultures caused a long-lasting stimulation of adenylate cyclase activity, and this was followed by increases in seroton N-acetyltransferase and cyclic adenosine monophosphate phosphodiesterase activities. These effects of choleragen were not blocked by the beta-adrenoceptor antagonist propranolol, but the increases in cyclic adenosine monophosphate phosphodiesterase and serotonin N-acetyltransferase activities could be prevented by the protein synthesis inhibitor cycloheximide. The results indicate that cholera toxin can mimic the induction of pineal enzymes that normally follows beta-adrenoceptor activation and suggest that increased cyclic adenosine monophosphate is a necessary and sufficient signal for such changes in enzyme activity."} {"id": "PMID:178054", "title": "Hepatoma induced by thorium dioxide.", "content": "A 74-year-old man complained of anorexia and weight loss. Twenty-six years earlier he had received an injection of Thorotrast. A needle biopsy of the liver showed thorium dioxide granules and periportal fibrosis. On laparotomy, a hepatoma of the left lobe of the liver was discovered. Hepatic malignancy should be suspected in any patient with abnormal results of liver function tests, particularly an elevated level of alkaline phosphatase, who previously has had an injection of Thorotrast.", "contents": "Hepatoma induced by thorium dioxide. A 74-year-old man complained of anorexia and weight loss. Twenty-six years earlier he had received an injection of Thorotrast. A needle biopsy of the liver showed thorium dioxide granules and periportal fibrosis. On laparotomy, a hepatoma of the left lobe of the liver was discovered. Hepatic malignancy should be suspected in any patient with abnormal results of liver function tests, particularly an elevated level of alkaline phosphatase, who previously has had an injection of Thorotrast."} {"id": "PMID:178060", "title": "Technique of adrenalectomy for metastatic cancer of the breast.", "content": "The transabdominal approach to adrenalectomy offers many advantages in the patient with metastatic cancer of the breast who is likely to respond to an ablative operation. Information derived in the course of laparotomy is important in planning for adjunctive chemotherapy, and oophorectomy can be carried out through the same incision when indicated. The vena cava can be plicated in patients who are considered to be at riak for thromboembolic phenomenom.", "contents": "Technique of adrenalectomy for metastatic cancer of the breast. The transabdominal approach to adrenalectomy offers many advantages in the patient with metastatic cancer of the breast who is likely to respond to an ablative operation. Information derived in the course of laparotomy is important in planning for adjunctive chemotherapy, and oophorectomy can be carried out through the same incision when indicated. The vena cava can be plicated in patients who are considered to be at riak for thromboembolic phenomenom."} {"id": "PMID:178061", "title": "Management of optic neuritis.", "content": "To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess.", "contents": "Management of optic neuritis. To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess."} {"id": "PMID:178067", "title": "Localization of angiotensin converting enzyme (kininase II). I. Preparation of antibody-hemeoctapeptide conjugates.", "content": "Antibodies to pig lung angiotensin converting enzyme (kininase II) were conjugated to a heme-octapeptide (8-microperoxidase, 8-MP) derived from cytochrome c. 8-MP, which has only one reactive amine, was coupled to antibody in a two-step procedure using a bifunctional active ester, bis-succinyl succinate. In the first-step, 8-MP-succinyl succinate, a stable compound which can be stored. In a second step, the remaining active ester was used for coupling to reactive amines of the antibody. The conjugate consists of 1.6-2.3 8-MP moieties per antibody. Using these procedures, the formation of complex polymers is avoided. Each molecule of conjugate possesses both immunoreactivity and peroxidatic activity. The conjugate has been used to localize angiotensin converting enzyme along the plasma membrane and associated caveolae of pig aortic endothelial cells in culture.", "contents": "Localization of angiotensin converting enzyme (kininase II). I. Preparation of antibody-hemeoctapeptide conjugates. Antibodies to pig lung angiotensin converting enzyme (kininase II) were conjugated to a heme-octapeptide (8-microperoxidase, 8-MP) derived from cytochrome c. 8-MP, which has only one reactive amine, was coupled to antibody in a two-step procedure using a bifunctional active ester, bis-succinyl succinate. In the first-step, 8-MP-succinyl succinate, a stable compound which can be stored. In a second step, the remaining active ester was used for coupling to reactive amines of the antibody. The conjugate consists of 1.6-2.3 8-MP moieties per antibody. Using these procedures, the formation of complex polymers is avoided. Each molecule of conjugate possesses both immunoreactivity and peroxidatic activity. The conjugate has been used to localize angiotensin converting enzyme along the plasma membrane and associated caveolae of pig aortic endothelial cells in culture."} {"id": "PMID:178068", "title": "Localization of angiotensin converting enzyme (kininase II). II. Immunocytochemistry and immunofluorescence.", "content": "The cellular and subcellular sites of angiotensin converting enzyme (kininase II) in lung tissue and endothelial cells in culture were examined by immunocytochemical and immunofluorescence techniques. Converting enzyme is capable of inactivating bradykinin and of converting angiotensin I to its potent lower homolog, angiotensin II. Immunocytochemistry at the electron microscope level used goat anti- (pig lung and angiotensin converting enzyme) coupled to 11-MP (11-microperoxidase) via glutaraldehyde or to 8-MP (8-microperoxidase) via a bifunctional active ester, bis-succinyl succinate. The latter conjugate, which does not contain complex polymers, has been characterized in detail in terms of immunoreactivity and peroxidase activity.", "contents": "Localization of angiotensin converting enzyme (kininase II). II. Immunocytochemistry and immunofluorescence. The cellular and subcellular sites of angiotensin converting enzyme (kininase II) in lung tissue and endothelial cells in culture were examined by immunocytochemical and immunofluorescence techniques. Converting enzyme is capable of inactivating bradykinin and of converting angiotensin I to its potent lower homolog, angiotensin II. Immunocytochemistry at the electron microscope level used goat anti- (pig lung and angiotensin converting enzyme) coupled to 11-MP (11-microperoxidase) via glutaraldehyde or to 8-MP (8-microperoxidase) via a bifunctional active ester, bis-succinyl succinate. The latter conjugate, which does not contain complex polymers, has been characterized in detail in terms of immunoreactivity and peroxidase activity."} {"id": "PMID:178069", "title": "Cell remodeling in the fat body of an insect.", "content": "The fat body of the Lepidopteran, Calpodes ethlius, undergoes major functional changes during larval-adult metamorphosis. These changes occur in conjunction with extensive cell remodeling - a process whereby one population of cellular organelles is destroyed and replaced by another during development. Fat body organelles including mitochondria, microbodies, and RER are destroyed on a massive scale shortly before pupation (Locke and Collins, 1965; Locke and McMahon, 1971) a new populations of each are regenerated shortly after emergence of the adult. In addition, protein, lipid and RNA reserves formed shortly before pupation and multivesicular bodies formed shortly before emergence are secreted into the haemocoel during the first few days of adult life. Electron microscopic studies using tracer techniques, cytochemical and enzyme localization procedures, and sterological analyses have been undertaken to determine the time course and mechanism of organelle regeneration and the fate of reserves stored in the fat body.", "contents": "Cell remodeling in the fat body of an insect. The fat body of the Lepidopteran, Calpodes ethlius, undergoes major functional changes during larval-adult metamorphosis. These changes occur in conjunction with extensive cell remodeling - a process whereby one population of cellular organelles is destroyed and replaced by another during development. Fat body organelles including mitochondria, microbodies, and RER are destroyed on a massive scale shortly before pupation (Locke and Collins, 1965; Locke and McMahon, 1971) a new populations of each are regenerated shortly after emergence of the adult. In addition, protein, lipid and RNA reserves formed shortly before pupation and multivesicular bodies formed shortly before emergence are secreted into the haemocoel during the first few days of adult life. Electron microscopic studies using tracer techniques, cytochemical and enzyme localization procedures, and sterological analyses have been undertaken to determine the time course and mechanism of organelle regeneration and the fate of reserves stored in the fat body."} {"id": "PMID:178070", "title": "Effects of imipramine, nomifensine and d-amphetamine on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase.", "content": "The three dissimilar structural antidepressant drugs, imipramine, nomifensine and d-amphetamine, were compared for their effects on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. Three antidepressant drugs caused a dose-dependent inhibition on type B monoamine oxidase. Of the three drugs, imipramine had a most potent effect. Unlike d-amphetamine, both imipramine and nomifensine inhibited the cyclic AMP phosphodiesterase activity at concentrations more than 10(-4)M. No effect was observed below this concentration. All drugs seemed to have little or no effects on the partially purified dopamine-beta-hydroxylase activity. The weak inhibitory effects of nomifensine on these three enzymes may not be attributable to its antidepressant properties. Morphine had no effect on the three enzyme activities.", "contents": "Effects of imipramine, nomifensine and d-amphetamine on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. The three dissimilar structural antidepressant drugs, imipramine, nomifensine and d-amphetamine, were compared for their effects on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. Three antidepressant drugs caused a dose-dependent inhibition on type B monoamine oxidase. Of the three drugs, imipramine had a most potent effect. Unlike d-amphetamine, both imipramine and nomifensine inhibited the cyclic AMP phosphodiesterase activity at concentrations more than 10(-4)M. No effect was observed below this concentration. All drugs seemed to have little or no effects on the partially purified dopamine-beta-hydroxylase activity. The weak inhibitory effects of nomifensine on these three enzymes may not be attributable to its antidepressant properties. Morphine had no effect on the three enzyme activities."} {"id": "PMID:178072", "title": "Synthesis of potential antiprogestogens.", "content": "Acylated derivatives of 17 alpha-hydroxyprogesterone were prepared in order to test the hypothesis that dialkylamino alkyl moieties have the effect of transforming progestogens into antiprogestogens. This approach has been successful with certain estrogens. Compounds with other functional groups were synthesized to determine whether these might exert binding influence outside the area occupied by progesterone itself. The compounds were tested for competitive affinity against tritiated progesterone and receptor from rabbit uterus cytosol. The low affinity of all derivatives makes it unlikely that they would be active as antiprogestational agents.", "contents": "Synthesis of potential antiprogestogens. Acylated derivatives of 17 alpha-hydroxyprogesterone were prepared in order to test the hypothesis that dialkylamino alkyl moieties have the effect of transforming progestogens into antiprogestogens. This approach has been successful with certain estrogens. Compounds with other functional groups were synthesized to determine whether these might exert binding influence outside the area occupied by progesterone itself. The compounds were tested for competitive affinity against tritiated progesterone and receptor from rabbit uterus cytosol. The low affinity of all derivatives makes it unlikely that they would be active as antiprogestational agents."} {"id": "PMID:178073", "title": "Existence of receptors bound to endogenous estradiol in breast cancers of premenopausal and postmenopausal women.", "content": "The amounts of free and occupied estrogen receptors were determined in cytosols and cellular (cytoplasmic + nuclear) extracts of 23 human breast cancers. In vivo undersaturation of the receptors was observed in all tumors. A positive correlation was found between the degree of saturation and the concentration of circulating estrogens in premenopausal women. The saturation of the sites was higher in cellular extracts than in cytosols, pointing to the existence of receptor-estradiol complexes bound to nuclei. Our results suggest that the absolute number of occupied receptors depends upon the level of available cytoplasmic receptors as well as upon the level of tissue estradiol.", "contents": "Existence of receptors bound to endogenous estradiol in breast cancers of premenopausal and postmenopausal women. The amounts of free and occupied estrogen receptors were determined in cytosols and cellular (cytoplasmic + nuclear) extracts of 23 human breast cancers. In vivo undersaturation of the receptors was observed in all tumors. A positive correlation was found between the degree of saturation and the concentration of circulating estrogens in premenopausal women. The saturation of the sites was higher in cellular extracts than in cytosols, pointing to the existence of receptor-estradiol complexes bound to nuclei. Our results suggest that the absolute number of occupied receptors depends upon the level of available cytoplasmic receptors as well as upon the level of tissue estradiol."} {"id": "PMID:178074", "title": "Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15alpha,16alpha,17beta-tetrol).", "content": "The binding affinities for the catecholestrogen metabolites of estradiol and of their methyl ethers for the rat uterine cytosol estrogen receptors were examined. Similarly the binding of the fetal estradiol metabolite, 15alpha-hydroxyestriol (estertrol) was also measured. All of the catecholestrogens showed binding affinities far in excess of their uterotrophic potency. This is different from estriol, the product of the alternative metabolic pathways and suggests that the direction of estradiol metabolism may have an important role in the modulation of estrogenic activity of the female sex hormone.", "contents": "Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15alpha,16alpha,17beta-tetrol). The binding affinities for the catecholestrogen metabolites of estradiol and of their methyl ethers for the rat uterine cytosol estrogen receptors were examined. Similarly the binding of the fetal estradiol metabolite, 15alpha-hydroxyestriol (estertrol) was also measured. All of the catecholestrogens showed binding affinities far in excess of their uterotrophic potency. This is different from estriol, the product of the alternative metabolic pathways and suggests that the direction of estradiol metabolism may have an important role in the modulation of estrogenic activity of the female sex hormone."} {"id": "PMID:178075", "title": "Water-soluble metabolites of the estrogens. Quantitation of C-18 tetrols in rat feces.", "content": "Several radioactive estrogens possessing one, two and three hydroxyl groups were injected orally (and in the case of estrone sulfate also intraperitoneally) into adult male rats. The rats were either intact or had ligated or cannulated bile ducts. Two unconjugated estrogen tetrols together represented 21 - 87% of the total metabolites in the intact rat. One of the tetrols was 2-hydroxyestriol (estra-1,3,5(10)-triene-2,3,16alpha,17beta-tetrol); the other may be estra-1,3,5(10)-triene-2,3,6xi,17beta-tetrol but this was not confirmed. It is concluded that poly-hydroxylated estrogens represent a very large proportion of the previously unidentified water-soluble metabolites of the estrogens in the adult male rat.", "contents": "Water-soluble metabolites of the estrogens. Quantitation of C-18 tetrols in rat feces. Several radioactive estrogens possessing one, two and three hydroxyl groups were injected orally (and in the case of estrone sulfate also intraperitoneally) into adult male rats. The rats were either intact or had ligated or cannulated bile ducts. Two unconjugated estrogen tetrols together represented 21 - 87% of the total metabolites in the intact rat. One of the tetrols was 2-hydroxyestriol (estra-1,3,5(10)-triene-2,3,16alpha,17beta-tetrol); the other may be estra-1,3,5(10)-triene-2,3,6xi,17beta-tetrol but this was not confirmed. It is concluded that poly-hydroxylated estrogens represent a very large proportion of the previously unidentified water-soluble metabolites of the estrogens in the adult male rat."} {"id": "PMID:178076", "title": "Specific progesterone receptors in dimethylbenzanthracene (DMBA)-induced mammary tumors.", "content": "Properties of a progesterone receptor present in the cytosol (105,000 xg supernatant) of dimethylbenzanthracene (DMBA)-induced mammary tumors were studied using the highly potent progestin [3H]R 5020 (17, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione). As shown by sucrose gradient analysis, specific binding of [3H] R 5020 is associated with components migrating at 7-8S and 4S. Low affinity binding of the synthetic progestin is eliminated by treatment with dextran-coated charcoal. [3H] R 5020 binding is highly progestin-specific since it is easily displaced by unlabelled norgestrel, R 5020 and progesterone while estradiol-17beta, dihydrotestosterone, testosterone, testosterone and diethylstilbestrol have much lower activity. Dexamethasone and cortisol have little, if any, effect on [3H] R 5020 binding.", "contents": "Specific progesterone receptors in dimethylbenzanthracene (DMBA)-induced mammary tumors. Properties of a progesterone receptor present in the cytosol (105,000 xg supernatant) of dimethylbenzanthracene (DMBA)-induced mammary tumors were studied using the highly potent progestin [3H]R 5020 (17, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione). As shown by sucrose gradient analysis, specific binding of [3H] R 5020 is associated with components migrating at 7-8S and 4S. Low affinity binding of the synthetic progestin is eliminated by treatment with dextran-coated charcoal. [3H] R 5020 binding is highly progestin-specific since it is easily displaced by unlabelled norgestrel, R 5020 and progesterone while estradiol-17beta, dihydrotestosterone, testosterone, testosterone and diethylstilbestrol have much lower activity. Dexamethasone and cortisol have little, if any, effect on [3H] R 5020 binding."} {"id": "PMID:178078", "title": "A survey of hospital services for suicidal persons.", "content": "A person who threatens or attempts suicide, arriving for treatment at any 1 of 10 hospitals serving a suburban area in the Bay Area of California, will be met with a variety of responses by different kinds of personnel, depending on the hospital to which he comes. In half of the hospitals, he could be subsequently discharged without psychiatric consultation of any kind. Follow-through on any outpatient referral would usually be left up to him. Although a few hospitals attend to the problem of suicidal persons in many important respects, other hospitals pay little attention to these same aspects. Because of the important role of the hospital in the prevention of suicide, it is recommended that the hospital's function in dealing with suicidal patients be better defined, extended, and made more consistent.", "contents": "A survey of hospital services for suicidal persons. A person who threatens or attempts suicide, arriving for treatment at any 1 of 10 hospitals serving a suburban area in the Bay Area of California, will be met with a variety of responses by different kinds of personnel, depending on the hospital to which he comes. In half of the hospitals, he could be subsequently discharged without psychiatric consultation of any kind. Follow-through on any outpatient referral would usually be left up to him. Although a few hospitals attend to the problem of suicidal persons in many important respects, other hospitals pay little attention to these same aspects. Because of the important role of the hospital in the prevention of suicide, it is recommended that the hospital's function in dealing with suicidal patients be better defined, extended, and made more consistent."} {"id": "PMID:178079", "title": "The value of amoebic serology in an area of low endemicity.", "content": "One hundred sera from army patients who had had amoebiasis in the past and 113 sera from coloured immigrants attending a venereal diseases clinic were examined by four serological techniques. The indirect haemagglutination and the latex agglutination tests showed almost complete correlation; they are useful epidemiological tools but too sensitive and the antibodies on which they depend are too persistent for clinical use. The indirect fluorescent antibody test is a good clinical screening test, and in an area of low endemicity the gel diffusion precipitin test shows a close correlation with clinical disease.", "contents": "The value of amoebic serology in an area of low endemicity. One hundred sera from army patients who had had amoebiasis in the past and 113 sera from coloured immigrants attending a venereal diseases clinic were examined by four serological techniques. The indirect haemagglutination and the latex agglutination tests showed almost complete correlation; they are useful epidemiological tools but too sensitive and the antibodies on which they depend are too persistent for clinical use. The indirect fluorescent antibody test is a good clinical screening test, and in an area of low endemicity the gel diffusion precipitin test shows a close correlation with clinical disease."} {"id": "PMID:178080", "title": "In vitro sensitivity of Entamoeba histolytica to furazolidone and iodochlorhydroxyquin, separate and combined.", "content": "Entamoeba histolytica trophozoites isolated in Robinson's medium from faeces containing cysts, transported from India, have been tested in vitro against the drugs furazolidone, iodochlorhydroxyquin, and both drugs combined as Dependal. Results show the levels at which drug action is significant and that interaction between the drugs occurs at two concentrations.", "contents": "In vitro sensitivity of Entamoeba histolytica to furazolidone and iodochlorhydroxyquin, separate and combined. Entamoeba histolytica trophozoites isolated in Robinson's medium from faeces containing cysts, transported from India, have been tested in vitro against the drugs furazolidone, iodochlorhydroxyquin, and both drugs combined as Dependal. Results show the levels at which drug action is significant and that interaction between the drugs occurs at two concentrations."} {"id": "PMID:178077", "title": "Pyridine nucleotide redox state and blood flow of the cerebral cortex following middle cerebral artery occlusion in the cat.", "content": "Acute changes in the redox state of NADH in the cerebral cortex of cats were investigated following occlusion of the middle cerebral cortex (MCA) and were correlated with alterations of regional cerebral blood flow in the ischemic cortex determined autoradiographically. Arterial occlusion was accomplished via the transorbital approach. Cortical fluorescence and reflected light signals were recorded from the central MCA territory by means of a beam-splitting fluorometer, and a fluorescence signal corrected for alterations in intravascular hemoglobin was derived. Following arterial occlusion, there was a rapid increase in cortical NADH fluorescence, peaking within 30 to 70 seconds at 20% to 40% of full scale. This was followed by a slow linear decline in fluorescence over the next several minutes. The behavior of cortical NADH fluorescence was unaffected by replacement of the ambient air over the cortical surface with nitrogen. Mean regional blood flow values in the most ischemic gyri two to 15 minutes following arterial occlusion were 21% to 23% of the corresponding values in the opposite, nonischemic hemisphere. In individual animals, peak NADH fluorescence values following arterial occlusion correlated with the extent of blood flow reduction in the affected ischemic gyri (P less than 0.05).", "contents": "Pyridine nucleotide redox state and blood flow of the cerebral cortex following middle cerebral artery occlusion in the cat. Acute changes in the redox state of NADH in the cerebral cortex of cats were investigated following occlusion of the middle cerebral cortex (MCA) and were correlated with alterations of regional cerebral blood flow in the ischemic cortex determined autoradiographically. Arterial occlusion was accomplished via the transorbital approach. Cortical fluorescence and reflected light signals were recorded from the central MCA territory by means of a beam-splitting fluorometer, and a fluorescence signal corrected for alterations in intravascular hemoglobin was derived. Following arterial occlusion, there was a rapid increase in cortical NADH fluorescence, peaking within 30 to 70 seconds at 20% to 40% of full scale. This was followed by a slow linear decline in fluorescence over the next several minutes. The behavior of cortical NADH fluorescence was unaffected by replacement of the ambient air over the cortical surface with nitrogen. Mean regional blood flow values in the most ischemic gyri two to 15 minutes following arterial occlusion were 21% to 23% of the corresponding values in the opposite, nonischemic hemisphere. In individual animals, peak NADH fluorescence values following arterial occlusion correlated with the extent of blood flow reduction in the affected ischemic gyri (P less than 0.05)."} {"id": "PMID:178083", "title": "Ileal conduit urinary diversion. Ten-year review.", "content": "The experience with ileal conduit urinary diversion at Emory University and Affiliated Hospitals over a ten-year period is presented. Included in this review are patients with benign and malignant disease. The indications, technique, results, and complications of this type of urinary diversion are considered. Some differences between ileal conduit diversion of children and adults are discussed.", "contents": "Ileal conduit urinary diversion. Ten-year review. The experience with ileal conduit urinary diversion at Emory University and Affiliated Hospitals over a ten-year period is presented. Included in this review are patients with benign and malignant disease. The indications, technique, results, and complications of this type of urinary diversion are considered. Some differences between ileal conduit diversion of children and adults are discussed."} {"id": "PMID:178084", "title": "Aerobic and anaerobic flora in bladder urine of patients with indwelling urethral catheters.", "content": "Twenty-five bladder urine specimens from 13 patients with long-standing indwelling catheters were obtained by percutaneous suprapubic needle aspiration to avoid contamination by extraneous flora and cultured aerobically and anaerobically. Twenty different species of organism were isolated from twenty-four positive specimens. The isolates were predominantly gram-negative aerobic or facultatively anaerobic bacilli, with occasional gram-positive aerobic cocci and yeasts. One patient had Clostridium perfringens and a Bifidobacterium and another had Veillonella and two species of Bifidobacterium. Both patients had four concomitant aerobic or facultative bacteria present. Anaerobic bacteria may therefore be found in the bladder urine of some patients with indwelling urethral catheters, but their role in the initiation and perpetuation of urinary tract infection in this setting remains unclear.", "contents": "Aerobic and anaerobic flora in bladder urine of patients with indwelling urethral catheters. Twenty-five bladder urine specimens from 13 patients with long-standing indwelling catheters were obtained by percutaneous suprapubic needle aspiration to avoid contamination by extraneous flora and cultured aerobically and anaerobically. Twenty different species of organism were isolated from twenty-four positive specimens. The isolates were predominantly gram-negative aerobic or facultatively anaerobic bacilli, with occasional gram-positive aerobic cocci and yeasts. One patient had Clostridium perfringens and a Bifidobacterium and another had Veillonella and two species of Bifidobacterium. Both patients had four concomitant aerobic or facultative bacteria present. Anaerobic bacteria may therefore be found in the bladder urine of some patients with indwelling urethral catheters, but their role in the initiation and perpetuation of urinary tract infection in this setting remains unclear."} {"id": "PMID:178081", "title": "[Drug resistance and hormone dependence of a case of breast cancer].", "content": "A case of breast cancer was treated with mastectomy followed by cyclical combination chemotherapy with CMF for a year. In the course of chemotherapy cancer developed in the contralateral breast. Mastectomy was followed within two months by lung metastases. After ovariectomy the lung metastases cleared almost completely. The case shown how the hormone dependence of a breast cancer can remain unimpaired even after prolonged chemotherapy and notwithstanding its failure and secondly that amenorrhea due to chemotherapy need not mean endocrine failure of the ovary.", "contents": "[Drug resistance and hormone dependence of a case of breast cancer]. A case of breast cancer was treated with mastectomy followed by cyclical combination chemotherapy with CMF for a year. In the course of chemotherapy cancer developed in the contralateral breast. Mastectomy was followed within two months by lung metastases. After ovariectomy the lung metastases cleared almost completely. The case shown how the hormone dependence of a breast cancer can remain unimpaired even after prolonged chemotherapy and notwithstanding its failure and secondly that amenorrhea due to chemotherapy need not mean endocrine failure of the ovary."} {"id": "PMID:178086", "title": "[Phosphatase activity of the neutrophils in acute appendicitis in children].", "content": "Phosphatase activity of neutrophils was studied in 342 patients directed to the hospital with the diagnosis of acute appendicitis, and in 56 healthy children. The index of phosphatase activity of neutrophils (IPAN) was found to be considerably increased in all forms of appendicitis in childhood. An intensity of the reaction depends on the form and terms, elapsed since the disease onset. The determination of IPAN in the complex with clinical findings could be utilized for the differential diagnosis purposes in investigation of patients suspected of acute appendicitis, while in the postoperative period - for estimating a gravity of the course and prognosis of the disease.", "contents": "[Phosphatase activity of the neutrophils in acute appendicitis in children]. Phosphatase activity of neutrophils was studied in 342 patients directed to the hospital with the diagnosis of acute appendicitis, and in 56 healthy children. The index of phosphatase activity of neutrophils (IPAN) was found to be considerably increased in all forms of appendicitis in childhood. An intensity of the reaction depends on the form and terms, elapsed since the disease onset. The determination of IPAN in the complex with clinical findings could be utilized for the differential diagnosis purposes in investigation of patients suspected of acute appendicitis, while in the postoperative period - for estimating a gravity of the course and prognosis of the disease."} {"id": "PMID:178088", "title": "Practical aspects of equine virus abortion in the United Kingdom.", "content": "The current knowledge of the clinical signs, epidemiology and pathogenesis of abortion due to the equid herpesvirus (EHV 1) is reviewed. The relationship between the respiratory and abortigenic forms of the disease is discussed as well as the low incidence of virus abortion in the UK compared to some other parts of the world. Some practical aspects of the disease as they affect stud management are considered including methods of diagnosis, prophylaxis and the necessary action to be taken to prevent spread of infection.", "contents": "Practical aspects of equine virus abortion in the United Kingdom. The current knowledge of the clinical signs, epidemiology and pathogenesis of abortion due to the equid herpesvirus (EHV 1) is reviewed. The relationship between the respiratory and abortigenic forms of the disease is discussed as well as the low incidence of virus abortion in the UK compared to some other parts of the world. Some practical aspects of the disease as they affect stud management are considered including methods of diagnosis, prophylaxis and the necessary action to be taken to prevent spread of infection."} {"id": "PMID:178090", "title": "Effect of ceruloplasmin on Sendai virus multiplication in chorioallantoic membrane fragments.", "content": "Three stages can be distinguished in the evolution of HA titer during Sendai virus multiplication in chorioallantoic membrane (CAM) fragments in relation to the age of CAM and conditions of inoculation and maintenance. Ceruloplasmin has an inhibitory effect on virus multiplication, more marked in the case of stationarily maintained CAM fragments and dependent on the relationship between the moment of ceruloplasmin addition and of virus inoculation. Maximum inhibition is achieved by inoculation of Sendai virus (1 Ha u) after 4 1/2-hour preincubation with ceruloplasmin (5 x 10(-7)M). The experimental data plead for the formation of a virus-ceruloplasmin complex able to inhibit both penetration and release of virus synthesized in the cell.", "contents": "Effect of ceruloplasmin on Sendai virus multiplication in chorioallantoic membrane fragments. Three stages can be distinguished in the evolution of HA titer during Sendai virus multiplication in chorioallantoic membrane (CAM) fragments in relation to the age of CAM and conditions of inoculation and maintenance. Ceruloplasmin has an inhibitory effect on virus multiplication, more marked in the case of stationarily maintained CAM fragments and dependent on the relationship between the moment of ceruloplasmin addition and of virus inoculation. Maximum inhibition is achieved by inoculation of Sendai virus (1 Ha u) after 4 1/2-hour preincubation with ceruloplasmin (5 x 10(-7)M). The experimental data plead for the formation of a virus-ceruloplasmin complex able to inhibit both penetration and release of virus synthesized in the cell."} {"id": "PMID:178091", "title": "Studies on the presence of viral antibodies in patients with various forms of malignant neoplasia.", "content": "The study of viral antibodies in 6714 sera demonstrated that the level of antibodies to infectious viruses was the same in cancer patients as in controls. However, the patients with various forms of neoplasia showed a considerable percentage and high antibody levels to viruses with oncogenic potential for animals (adenovirus, SV40, Rous virus) or involved in human carcinogenesis (herpes virus).", "contents": "Studies on the presence of viral antibodies in patients with various forms of malignant neoplasia. The study of viral antibodies in 6714 sera demonstrated that the level of antibodies to infectious viruses was the same in cancer patients as in controls. However, the patients with various forms of neoplasia showed a considerable percentage and high antibody levels to viruses with oncogenic potential for animals (adenovirus, SV40, Rous virus) or involved in human carcinogenesis (herpes virus)."} {"id": "PMID:178103", "title": "[Transfer of the genetic information of oncornaviruses by means of tumor cell DNA].", "content": "The infection process was reproduced in the culture of chick embryonal cells by means of: a) DNA isolated from chick Rous sarcoma (Carr-Zilber strain); b) DNA from blood cells of chicks with myeloblastosis (strain A); c) DNA from Rous virus malignified (Prague strain) rat cells (XC). Antigenic properties of the virus, transfected with DNA from chick Rous sarcoma, would differ from the original parental strain (Carr-Zilber RSV), that evidences the possibility of a partial transfer of genetic information in transfection. A suggestion is made on four presumable variants of oncornaviruses transfection by means of tumor cells DNA.", "contents": "[Transfer of the genetic information of oncornaviruses by means of tumor cell DNA]. The infection process was reproduced in the culture of chick embryonal cells by means of: a) DNA isolated from chick Rous sarcoma (Carr-Zilber strain); b) DNA from blood cells of chicks with myeloblastosis (strain A); c) DNA from Rous virus malignified (Prague strain) rat cells (XC). Antigenic properties of the virus, transfected with DNA from chick Rous sarcoma, would differ from the original parental strain (Carr-Zilber RSV), that evidences the possibility of a partial transfer of genetic information in transfection. A suggestion is made on four presumable variants of oncornaviruses transfection by means of tumor cells DNA."} {"id": "PMID:178104", "title": "[Ultrastructural characteristics of experimental tumors of the intestine].", "content": "Tumors of the rat large intestine induced by subcutaneous injection of 1,2-dimethylhydrazine were studied by the method of electron microscopy. Adenocarcinomas retained histiotypical differentiation and at the same time consisted mostly of cells with a low rate of differentiation. Just on the contrary, in mucous and signet-ring cell carcinomas the picture of an advanced cell differentiation was observed in a complete loss of organogeny. The greatest malignancy of neoplasms (signet-ring carcinoma), which cells are characterized by a high degree of cytological differentiation, is a manifestation of independence of tumor progression signs.", "contents": "[Ultrastructural characteristics of experimental tumors of the intestine]. Tumors of the rat large intestine induced by subcutaneous injection of 1,2-dimethylhydrazine were studied by the method of electron microscopy. Adenocarcinomas retained histiotypical differentiation and at the same time consisted mostly of cells with a low rate of differentiation. Just on the contrary, in mucous and signet-ring cell carcinomas the picture of an advanced cell differentiation was observed in a complete loss of organogeny. The greatest malignancy of neoplasms (signet-ring carcinoma), which cells are characterized by a high degree of cytological differentiation, is a manifestation of independence of tumor progression signs."} {"id": "PMID:178109", "title": "[Pancreas carcinoma in the rat (attempts at implantation)].", "content": "It is reported on the technique of transplantation of a carcinoma on the pancreas of the rat. As to the origin the malignoma used is a tumour induced by Methyl-Yellow and known as solid form of the Zajdela-hepatoma. Out of 50 transplantation experiments 48 were successful (96%). After continuous growth regional formations of metastases were observed. Death took place in the 3rd week after transgression of the borders of the organs under the picture of cachexia.", "contents": "[Pancreas carcinoma in the rat (attempts at implantation)]. It is reported on the technique of transplantation of a carcinoma on the pancreas of the rat. As to the origin the malignoma used is a tumour induced by Methyl-Yellow and known as solid form of the Zajdela-hepatoma. Out of 50 transplantation experiments 48 were successful (96%). After continuous growth regional formations of metastases were observed. Death took place in the 3rd week after transgression of the borders of the organs under the picture of cachexia."} {"id": "PMID:178110", "title": "[Adenosine-3', 5' -monophosphate in amniotic fluid of normal and high-risk pregnancy (author's transl)].", "content": "Transfer of information by cyclic AMP (cAMP) is an important principle of hormonal regulation. The endocrine and metabolic changes during pregnancy may result from a changed cAMP metabolism. At the beginning of systematic investigations on this complex of problems we determined the cAMP content in 111 samples of amniotic fluid from 104 pregnant women without risk symptoms between the eleventh and fortieth week of pregnancy. Up to the 20th week of pregnancy the cAMP content of the amniotic fluid remains constant (5 - 15pmol/ml) and subsequently rises (40th week: 19 - 35pmol/ml). We compared the cAMP content of 27 amniotic fluid samples from 22 risk pregnancies with the normal range which was established in this way. Higher levels of cAMP were measured in the amniotic fluid of women with hypertonic toxemia of pregnancy, gestational diabetes and intrauterine malnutrition - especially in relation to the birth weight. The various possible interpretations for this behavior must be clarified by further investigations.", "contents": "[Adenosine-3', 5' -monophosphate in amniotic fluid of normal and high-risk pregnancy (author's transl)]. Transfer of information by cyclic AMP (cAMP) is an important principle of hormonal regulation. The endocrine and metabolic changes during pregnancy may result from a changed cAMP metabolism. At the beginning of systematic investigations on this complex of problems we determined the cAMP content in 111 samples of amniotic fluid from 104 pregnant women without risk symptoms between the eleventh and fortieth week of pregnancy. Up to the 20th week of pregnancy the cAMP content of the amniotic fluid remains constant (5 - 15pmol/ml) and subsequently rises (40th week: 19 - 35pmol/ml). We compared the cAMP content of 27 amniotic fluid samples from 22 risk pregnancies with the normal range which was established in this way. Higher levels of cAMP were measured in the amniotic fluid of women with hypertonic toxemia of pregnancy, gestational diabetes and intrauterine malnutrition - especially in relation to the birth weight. The various possible interpretations for this behavior must be clarified by further investigations."} {"id": "PMID:178112", "title": "Transplacental effects of ethylnitrosourea precursors ethylurea and sodium nitrite in hamsters.", "content": "Four simultaneous dosages of the ethylnitrosourea precursors, ethylurea and sodium nitrite, were administered intragastrically to pregnant hamsters at 100 mg/kg and 50 mg/kg respectively, from the 12-15th days of pregnancy. The treatment induced multiple neurogenic tumors of the peripheral nervous system in the offspring. Female progeny developed a greater incidence and multiplicity of peripheral nervous system tumors with significantly shorter latencies than males, thus establishing evidence that the tumors were age and sex dependent. The tumors presented varied morphological patterns and upon transplantation, grew regularly, exhibiting their malignant nature. The possible influence of estrogenic hormones on the development and growth of peripheral nervous system tumors and comparative aspects of the relationship between prenatal and postnatal carcinogenesis with regard to the ensuing tumor spectra as a consequence of exposure to the same chemical agent, are discussed.", "contents": "Transplacental effects of ethylnitrosourea precursors ethylurea and sodium nitrite in hamsters. Four simultaneous dosages of the ethylnitrosourea precursors, ethylurea and sodium nitrite, were administered intragastrically to pregnant hamsters at 100 mg/kg and 50 mg/kg respectively, from the 12-15th days of pregnancy. The treatment induced multiple neurogenic tumors of the peripheral nervous system in the offspring. Female progeny developed a greater incidence and multiplicity of peripheral nervous system tumors with significantly shorter latencies than males, thus establishing evidence that the tumors were age and sex dependent. The tumors presented varied morphological patterns and upon transplantation, grew regularly, exhibiting their malignant nature. The possible influence of estrogenic hormones on the development and growth of peripheral nervous system tumors and comparative aspects of the relationship between prenatal and postnatal carcinogenesis with regard to the ensuing tumor spectra as a consequence of exposure to the same chemical agent, are discussed."} {"id": "PMID:178113", "title": "Transplantable, STH-producing and diabetogenic pituitary adenoma of the BD IX-strain of rats.", "content": "A chromophobic pituitary adenoma induced on BD IX-rats has been grafted on animals of the same strain. The transplanted tumour takes in 90-100%; it grows at a slow rate (in 7 months after grafting a weight of 7-20 g is attained). Tumour-bearing animals display gigantism and hypertrophy of adrenals; moreover, in 33% of cases, diabetes is observed. With non-diabetic animals, splenomegaly and marked leukocytosis are observed; immature white and red cells are present in the peripheral blood. Spontaneous regression of the tumour never occurs. After surgical removal, tumour regrowth and the formation of metastases are observed. Diabetes is characterised by pronounced hyperglycaemia, glucosuria, polyphagia and polydipsia. Histochemically, insulin cannot be detected in pancreas. Splenomegaly is never observed in diabetic animals. Transplanted adenoma frequently tends to stop growing. No recurrence is observable after extirpation. Spontaneous regression of the tumour sometimes occurs. Gigantism, hypertrophy of adrenals and diabetes are considered as consequences of growth hormone- and ACTH-secretion of the transplanted adenoma. At present the tumour is running in the 8th passage. It did not change its characteristics over a period of 5 years.", "contents": "Transplantable, STH-producing and diabetogenic pituitary adenoma of the BD IX-strain of rats. A chromophobic pituitary adenoma induced on BD IX-rats has been grafted on animals of the same strain. The transplanted tumour takes in 90-100%; it grows at a slow rate (in 7 months after grafting a weight of 7-20 g is attained). Tumour-bearing animals display gigantism and hypertrophy of adrenals; moreover, in 33% of cases, diabetes is observed. With non-diabetic animals, splenomegaly and marked leukocytosis are observed; immature white and red cells are present in the peripheral blood. Spontaneous regression of the tumour never occurs. After surgical removal, tumour regrowth and the formation of metastases are observed. Diabetes is characterised by pronounced hyperglycaemia, glucosuria, polyphagia and polydipsia. Histochemically, insulin cannot be detected in pancreas. Splenomegaly is never observed in diabetic animals. Transplanted adenoma frequently tends to stop growing. No recurrence is observable after extirpation. Spontaneous regression of the tumour sometimes occurs. Gigantism, hypertrophy of adrenals and diabetes are considered as consequences of growth hormone- and ACTH-secretion of the transplanted adenoma. At present the tumour is running in the 8th passage. It did not change its characteristics over a period of 5 years."} {"id": "PMID:178114", "title": "[Effect of the experimentally induced stress situation on the vascular wall in the rabbit].", "content": "DCS and ACTH causes an increasing cellular proliferation in the arterial wall of the rabbit. The combination of both shows only a small further increasing. The importance of these experiments is thought as an additional cause in the atherosclerotic vessel wall alteration.", "contents": "[Effect of the experimentally induced stress situation on the vascular wall in the rabbit]. DCS and ACTH causes an increasing cellular proliferation in the arterial wall of the rabbit. The combination of both shows only a small further increasing. The importance of these experiments is thought as an additional cause in the atherosclerotic vessel wall alteration."} {"id": "PMID:178115", "title": "[Aseptic necrosis of head of femur and disturbance of fat-metabolism type IIa after Fredrickson (author's transl)].", "content": "The history of aseptic necrosis of the head of femur is given. Following publication of osteonecrosis in hyperlipoproteinemia type IV after Fredrickson, now for the first time the relation between aseptic necrosis of the femoral head and the primary disturbance of fat metabolism type II is revealed. There exists a hypercholesterinemia, more exactly a hyperbeta-cholesterinemia. The subgroups type IIa and type IIb are explained. Type II is of particular importance since it produces early arteriosclerosis which demands early diagnosis, since this condition can be treated by drugs and diet. In the writers' opinion further differentiation of dys-and hyperlipidemiae in aseptic necrosis of the femoral head will enable us to define signs of disturbances of lipid metabolism. The group of \"idiopathic\" necroses of the femoral head will become steadily smaller. According to this basic concept the hypothesis might be put forward that this type of aseptic osteonecrosis is a late complication of a differentiated fat-metabolic disturbance.", "contents": "[Aseptic necrosis of head of femur and disturbance of fat-metabolism type IIa after Fredrickson (author's transl)]. The history of aseptic necrosis of the head of femur is given. Following publication of osteonecrosis in hyperlipoproteinemia type IV after Fredrickson, now for the first time the relation between aseptic necrosis of the femoral head and the primary disturbance of fat metabolism type II is revealed. There exists a hypercholesterinemia, more exactly a hyperbeta-cholesterinemia. The subgroups type IIa and type IIb are explained. Type II is of particular importance since it produces early arteriosclerosis which demands early diagnosis, since this condition can be treated by drugs and diet. In the writers' opinion further differentiation of dys-and hyperlipidemiae in aseptic necrosis of the femoral head will enable us to define signs of disturbances of lipid metabolism. The group of \"idiopathic\" necroses of the femoral head will become steadily smaller. According to this basic concept the hypothesis might be put forward that this type of aseptic osteonecrosis is a late complication of a differentiated fat-metabolic disturbance."} {"id": "PMID:178120", "title": "[Cycloalkylsulfamic acids and their salts. i.v. (author's transl)].", "content": "The sodium salts of cis- and trans-2-methyl-cyclohexylsulfamic acid were synthesized and tasted. There is no difference in their degree of sweetness.", "contents": "[Cycloalkylsulfamic acids and their salts. i.v. (author's transl)]. The sodium salts of cis- and trans-2-methyl-cyclohexylsulfamic acid were synthesized and tasted. There is no difference in their degree of sweetness."} {"id": "PMID:178121", "title": "[Determination of sulphydryl and disulphide groups in proteins by amperometric titration. III. Investigation of the specifity of Ag+ ions for protein SH groups (author's transl)].", "content": "The specifity of Ag+ ions for protein SH groups has been questioned frequently, even though the amperometric titration with AgNO3 is one of the most common methods for the determination of SH groups in proteins. This is due to the fact, that the formation of silver complexes in the titration of cysteine causes a consumption of AgNO3 which is too high. In order to find out if this may be true in the case of proteins, in the present work select proteins with a well known content of SH and SS groups have been titrated amperometrically in tris buffer pH 7.4 with 0.001 M AgNO3. The proteins used were hemoglobin, bovine serum albumin, ovalbumin, lysozyme, pepsin, myoglobin, and cytochrome c. The direct and the indirect titrations of (a) native, (b) denatured, and (c) NaBH4 reduced proteins showed, that the expected consumption of AgNO3 was in no case exceeded. Therefore under the conditions used AgNO3 may be considered as a specific reagent for protein SH groups. High SH values as a result of the amperometric titration of proteins with silver nitrate, which have been published occasionally, may be due to incorrect estimation of the end point of the titration. The reducibility of SS groups depends on the kind of protein. Lysozyme and pepsin were already completely reduced at 23 degrees C, whereas bovine serum albumin needed 60 degrees C. The direct titration method was useful only in some cases for the detection of all SH groups originally present in the proteins or formed by reduction with NaBH4. On the other hand the indirect titration method gave maximum values, because the slowly reacting SH groups of proteins are also allowed to react and the resulting titration curves may be evaluated correctly.", "contents": "[Determination of sulphydryl and disulphide groups in proteins by amperometric titration. III. Investigation of the specifity of Ag+ ions for protein SH groups (author's transl)]. The specifity of Ag+ ions for protein SH groups has been questioned frequently, even though the amperometric titration with AgNO3 is one of the most common methods for the determination of SH groups in proteins. This is due to the fact, that the formation of silver complexes in the titration of cysteine causes a consumption of AgNO3 which is too high. In order to find out if this may be true in the case of proteins, in the present work select proteins with a well known content of SH and SS groups have been titrated amperometrically in tris buffer pH 7.4 with 0.001 M AgNO3. The proteins used were hemoglobin, bovine serum albumin, ovalbumin, lysozyme, pepsin, myoglobin, and cytochrome c. The direct and the indirect titrations of (a) native, (b) denatured, and (c) NaBH4 reduced proteins showed, that the expected consumption of AgNO3 was in no case exceeded. Therefore under the conditions used AgNO3 may be considered as a specific reagent for protein SH groups. High SH values as a result of the amperometric titration of proteins with silver nitrate, which have been published occasionally, may be due to incorrect estimation of the end point of the titration. The reducibility of SS groups depends on the kind of protein. Lysozyme and pepsin were already completely reduced at 23 degrees C, whereas bovine serum albumin needed 60 degrees C. The direct titration method was useful only in some cases for the detection of all SH groups originally present in the proteins or formed by reduction with NaBH4. On the other hand the indirect titration method gave maximum values, because the slowly reacting SH groups of proteins are also allowed to react and the resulting titration curves may be evaluated correctly."} {"id": "PMID:178122", "title": "Adrenocorticotropic hormone, glucose and displacement activities in pigeons.", "content": "The possibility that displacement activities might be consequences of stress-induced humoral responses was investigated. Adrenocorticotropic hormone and glucose were injected into the brain ventricles of unrestrained domestic pigeons. ACTH leads to an increased frequency of yawning and headshaking and glucose to a decrease in arousal. It is concluded that these behavioural responses correspond partly with the displacement activities shown by birds. The role of the cerebrospinal fluid as a mediator of behaviourally active substances is discussed.", "contents": "Adrenocorticotropic hormone, glucose and displacement activities in pigeons. The possibility that displacement activities might be consequences of stress-induced humoral responses was investigated. Adrenocorticotropic hormone and glucose were injected into the brain ventricles of unrestrained domestic pigeons. ACTH leads to an increased frequency of yawning and headshaking and glucose to a decrease in arousal. It is concluded that these behavioural responses correspond partly with the displacement activities shown by birds. The role of the cerebrospinal fluid as a mediator of behaviourally active substances is discussed."} {"id": "PMID:178119", "title": "Hepatomegaly in Lusaka.", "content": "Pattern of hepatomegaly in Lusaka is studied. It appears that toxic hepatitis, viral hepatitis, hepatoma, cirrhosis and schistomasis play a major part in our set up in producing hepatic pathology.", "contents": "Hepatomegaly in Lusaka. Pattern of hepatomegaly in Lusaka is studied. It appears that toxic hepatitis, viral hepatitis, hepatoma, cirrhosis and schistomasis play a major part in our set up in producing hepatic pathology."} {"id": "PMID:178126", "title": "[Physico-chemical and serological study of agglutinogen 3 of B. pertussis].", "content": "Results of immunoelectrophoresis, gel-filtration and sedimentation analysis showed the preparation of agglutinogen 3 of B. pertussis to be homogenous. The principal physico-chemical characteristics of agglutinogen 3 (sedimentation constant, diffusion coefficient, molecular weight) were determined.", "contents": "[Physico-chemical and serological study of agglutinogen 3 of B. pertussis]. Results of immunoelectrophoresis, gel-filtration and sedimentation analysis showed the preparation of agglutinogen 3 of B. pertussis to be homogenous. The principal physico-chemical characteristics of agglutinogen 3 (sedimentation constant, diffusion coefficient, molecular weight) were determined."} {"id": "PMID:178127", "title": "[The effect of schizophrenic patients serum on the activity of several leukocyte enzymes].", "content": "A study of the activity of leukocyte enzymes in the blood of patients with nuclear forms of schizophrenia (52 cases) and in patients with circular schizophrenia (22 cases) depicted the following conditions. In the group of malignant schizophrenia, irrespective of the stage of the disease and in the group of circular forms there was a definite drop in the activity of cytochromoxidase, succinatedehydrogenase and MAO, while as the activity of the ATP-ase and peroxidase was increased. Supplementary animal experiments in vitro and in vivo made it possible to assume that these changes are due to the so-called serum factor.", "contents": "[The effect of schizophrenic patients serum on the activity of several leukocyte enzymes]. A study of the activity of leukocyte enzymes in the blood of patients with nuclear forms of schizophrenia (52 cases) and in patients with circular schizophrenia (22 cases) depicted the following conditions. In the group of malignant schizophrenia, irrespective of the stage of the disease and in the group of circular forms there was a definite drop in the activity of cytochromoxidase, succinatedehydrogenase and MAO, while as the activity of the ATP-ase and peroxidase was increased. Supplementary animal experiments in vitro and in vivo made it possible to assume that these changes are due to the so-called serum factor."} {"id": "PMID:178132", "title": "Oestradiol- and dihydrotestosterone receptors in normal and neoplastic human mammary tissue.", "content": "Human mammary gland and tumours derived from it contain individual receptors for oestradiol) and for dihydrotestosterone. Analysis of 97 mammary cancers by agargel electrophoresis revealed a widely varying pattern of simultaneous occurrence in different concentration ratios (46), sole presence of oestradiol receptor (23) or dihydrotestosterone receptor (8) and absence of both receptors (18). The relevance of the results is discussed and the need for an extensive cooperative study is emphasized.", "contents": "Oestradiol- and dihydrotestosterone receptors in normal and neoplastic human mammary tissue. Human mammary gland and tumours derived from it contain individual receptors for oestradiol) and for dihydrotestosterone. Analysis of 97 mammary cancers by agargel electrophoresis revealed a widely varying pattern of simultaneous occurrence in different concentration ratios (46), sole presence of oestradiol receptor (23) or dihydrotestosterone receptor (8) and absence of both receptors (18). The relevance of the results is discussed and the need for an extensive cooperative study is emphasized."} {"id": "PMID:178129", "title": "Electron microscopic observations on sputum in alveolar cell carcinoma.", "content": "This paper reports the techniques and results from the use of electron microscopy to augment the routine cytopathologic study of cells in sputum. The material for study consisted of specimens of sputum taken from a 75 year old white woman. The patient later died three months after the beginning of radiotherapy for alveolar cell carcinoma of the lung. Light microscopy revealed a homogenous population of cells, obviously malignant, and interpreted as being derived from alveolar cell carcinoma. Electron microscopic study showed prominent microvilli, numerous mitochondria, multiple foci of well-developed Golgi apparatus, and several types of lysosomes. The ultrastructure of these cells resembled that which has been described for type II alveolar cells from the lung.", "contents": "Electron microscopic observations on sputum in alveolar cell carcinoma. This paper reports the techniques and results from the use of electron microscopy to augment the routine cytopathologic study of cells in sputum. The material for study consisted of specimens of sputum taken from a 75 year old white woman. The patient later died three months after the beginning of radiotherapy for alveolar cell carcinoma of the lung. Light microscopy revealed a homogenous population of cells, obviously malignant, and interpreted as being derived from alveolar cell carcinoma. Electron microscopic study showed prominent microvilli, numerous mitochondria, multiple foci of well-developed Golgi apparatus, and several types of lysosomes. The ultrastructure of these cells resembled that which has been described for type II alveolar cells from the lung."} {"id": "PMID:178133", "title": "Inhibition o'f insulin release by cyproheptadine: effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets.", "content": "Cyproheptadine (1, 10 and 100 muM) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 muM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the beta-cell.", "contents": "Inhibition o'f insulin release by cyproheptadine: effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets. Cyproheptadine (1, 10 and 100 muM) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 muM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the beta-cell."} {"id": "PMID:178130", "title": "Eosinophilic granulocytes on the gastrocytogram.", "content": "The presence of eosinophilic granulocytes in the gastrocytogram requires examination is not specific and has to be clarified by repeated examinations. The patient should be kept under constant gastrocytologic control, because in certain cases the appearance of eosinophilic granulocytes may accompany cancer.", "contents": "Eosinophilic granulocytes on the gastrocytogram. The presence of eosinophilic granulocytes in the gastrocytogram requires examination is not specific and has to be clarified by repeated examinations. The patient should be kept under constant gastrocytologic control, because in certain cases the appearance of eosinophilic granulocytes may accompany cancer."} {"id": "PMID:178131", "title": "Preparation of islets of Langerhans from rabbits and hamsters by the collagenase digestion technique.", "content": "In this report we describe some modifications of the collagenase digestion technique for the preparation of pancreatic islets, that we have found helpful in preparing isolated islets of Langerhans from rabbits and hamsters. These modifications include disrupting the pancreatic acinar tissue by directly infiltrating it with Hanks' solution, periodically monitoring the progress of the collagenase digestion of the pancreatic tissue with the dissecting microscope, and purifying the islets by serial passage of the digested tissue through three Petri dishes containing Hanks' solution. This technique results in the successful isolation of the fragile and irregular rabbit islets as well as the isolation of the sturdier and more uniformly shaped hamster islets. The isolated respond to a glucose stimulus with an increase in radioimmunoassayable insulin secretion. We also describe a filtration technique for the preparation of isolated islets for histological examination. Isolated islets are retained on Millipore filters. The filters are then fixed, stained and mounted. Finally, we present realistic photographs of rabbit and hamster islets, as they appear under the dissecting microscope, during various stages of purification and isolation.", "contents": "Preparation of islets of Langerhans from rabbits and hamsters by the collagenase digestion technique. In this report we describe some modifications of the collagenase digestion technique for the preparation of pancreatic islets, that we have found helpful in preparing isolated islets of Langerhans from rabbits and hamsters. These modifications include disrupting the pancreatic acinar tissue by directly infiltrating it with Hanks' solution, periodically monitoring the progress of the collagenase digestion of the pancreatic tissue with the dissecting microscope, and purifying the islets by serial passage of the digested tissue through three Petri dishes containing Hanks' solution. This technique results in the successful isolation of the fragile and irregular rabbit islets as well as the isolation of the sturdier and more uniformly shaped hamster islets. The isolated respond to a glucose stimulus with an increase in radioimmunoassayable insulin secretion. We also describe a filtration technique for the preparation of isolated islets for histological examination. Isolated islets are retained on Millipore filters. The filters are then fixed, stained and mounted. Finally, we present realistic photographs of rabbit and hamster islets, as they appear under the dissecting microscope, during various stages of purification and isolation."} {"id": "PMID:178138", "title": "Genetic aspects of childhood tumours.", "content": "Present concepts on the etiology of childhood tumours are reviewed. The difference in clinical manifestations of the hereditary and nonhereditary types are illustrated with data on retinoblastoma and on nephroblastoma. Notwithstanding these differences it is most likely that the fundamental etiologic process is the same in both and that it consists in successive mutational events. The possible consequences of the association of retinoblastoma with a deletion of chromosome 13 in some cases are discussed. Several explanations for the association of Wilms' tumour and aniridia are also discussed.", "contents": "Genetic aspects of childhood tumours. Present concepts on the etiology of childhood tumours are reviewed. The difference in clinical manifestations of the hereditary and nonhereditary types are illustrated with data on retinoblastoma and on nephroblastoma. Notwithstanding these differences it is most likely that the fundamental etiologic process is the same in both and that it consists in successive mutational events. The possible consequences of the association of retinoblastoma with a deletion of chromosome 13 in some cases are discussed. Several explanations for the association of Wilms' tumour and aniridia are also discussed."} {"id": "PMID:178139", "title": "Hydrogen cyanide smell sensitivity in some Indian populations.", "content": "The ability to smell HCN has been examined in a sample of 2619 subjects from Hyderabad, Andhra Pradesh, belonging to different Indian ethnic groups. One single antimode, between concentrations of 5% and 10%, has been found. No sex nor ethnic differences were noted. Previous claims of possible sex-linked inheritance could not be confirmed.", "contents": "Hydrogen cyanide smell sensitivity in some Indian populations. The ability to smell HCN has been examined in a sample of 2619 subjects from Hyderabad, Andhra Pradesh, belonging to different Indian ethnic groups. One single antimode, between concentrations of 5% and 10%, has been found. No sex nor ethnic differences were noted. Previous claims of possible sex-linked inheritance could not be confirmed."} {"id": "PMID:178141", "title": "Heavy metal levels and delta-amino-levulinic acid dehydrase levels in peripheral polyneuropathy.", "content": "On the basis of assay of heavy metals in whole blood (lead, cadimum, chromium, copper, nickel and manganese) and delta-amino-levulinic-acid dehydrase (ALA-D) and ALA in urine in a normal Danish population, the levels of these clinco-chemical factors were assayed in 23 patients with peripheral neuropathy of unknown etiology. All patients studied showed electro-physiological sign of denervation and/or reduced motor or sensoric nerve conduction velocity. Cadmium and manganese were never found to be increased. In all but four patients, an increase of one or more heavy metals was found. Ten patients showed raised levels of two or more metals, the dominant metal being lead (10 cases), nine patients showed increased in chromium. A significant corrleation was found between increasing lead levels and decreasing ALA-D activity. Although normal concentrations of manganese were found, correlation analysis revealed a significant correlation between increased manganese and decreased ALA-D. The raised values of heavy metals could not be traced to occupational or other exposure to heavy metals and the increased values were not related to tobacco consumption. The findings are discussed in relation to known data on neuropathy and the results seem to indicate a multifactorial patholgenesis of the disease. Among factors contributing to the precipitation of the syndrome may be raised levels of heavy metals.", "contents": "Heavy metal levels and delta-amino-levulinic acid dehydrase levels in peripheral polyneuropathy. On the basis of assay of heavy metals in whole blood (lead, cadimum, chromium, copper, nickel and manganese) and delta-amino-levulinic-acid dehydrase (ALA-D) and ALA in urine in a normal Danish population, the levels of these clinco-chemical factors were assayed in 23 patients with peripheral neuropathy of unknown etiology. All patients studied showed electro-physiological sign of denervation and/or reduced motor or sensoric nerve conduction velocity. Cadmium and manganese were never found to be increased. In all but four patients, an increase of one or more heavy metals was found. Ten patients showed raised levels of two or more metals, the dominant metal being lead (10 cases), nine patients showed increased in chromium. A significant corrleation was found between increasing lead levels and decreasing ALA-D activity. Although normal concentrations of manganese were found, correlation analysis revealed a significant correlation between increased manganese and decreased ALA-D. The raised values of heavy metals could not be traced to occupational or other exposure to heavy metals and the increased values were not related to tobacco consumption. The findings are discussed in relation to known data on neuropathy and the results seem to indicate a multifactorial patholgenesis of the disease. Among factors contributing to the precipitation of the syndrome may be raised levels of heavy metals."} {"id": "PMID:178142", "title": "Ultrastructure of Lewy bodies in the stellate ganglion.", "content": "The Lewy body, a characteristic nerve cell inclusion in idiopathic parkinsonism, was examined by electron microscopy in the stellate ganglion, obtained from 9 patients at autopsy. Three main forms of Lewy bodies or Lewy body-related structures were demonstrated: A.Rare filamentous Lewy bodies, similar to Lewy bodies in the central nervous system. B. Granular Lewy bodies in nerve cell processes. C. Abnormal nerve cell processes, filled with heterogenous material. Large dense core vesicles were prominent in the last 2 forms. None of these abnormalities were found in 2 control groups consisting of 9 parkinsonism cases without central nervous system Lewy bodies, and 17 cases without parkinsonism. The filamentous Lewy body (type A) was found in the perikaryon and was surrounded by neuromelanin, whereas the other forms (type B and C) were seen in nerve cell processes. Mitochondrial inclusions, present mainly, but not exclusively, in neuromelanin-containing cells, were not related to Lewy body formation or to parkinsonism.", "contents": "Ultrastructure of Lewy bodies in the stellate ganglion. The Lewy body, a characteristic nerve cell inclusion in idiopathic parkinsonism, was examined by electron microscopy in the stellate ganglion, obtained from 9 patients at autopsy. Three main forms of Lewy bodies or Lewy body-related structures were demonstrated: A.Rare filamentous Lewy bodies, similar to Lewy bodies in the central nervous system. B. Granular Lewy bodies in nerve cell processes. C. Abnormal nerve cell processes, filled with heterogenous material. Large dense core vesicles were prominent in the last 2 forms. None of these abnormalities were found in 2 control groups consisting of 9 parkinsonism cases without central nervous system Lewy bodies, and 17 cases without parkinsonism. The filamentous Lewy body (type A) was found in the perikaryon and was surrounded by neuromelanin, whereas the other forms (type B and C) were seen in nerve cell processes. Mitochondrial inclusions, present mainly, but not exclusively, in neuromelanin-containing cells, were not related to Lewy body formation or to parkinsonism."} {"id": "PMID:178143", "title": "Extraocular muscles: light microscopy and ultrastructural features.", "content": "Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One mum thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2--3 mum sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres. Ultrastructural features consisted of vacuoles within myofilament bundles, \"smearing\" of Z bands, and \"nemaline rods\". Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. \"Leptomeric\" profiles, \"Zebra bodies\", or \"striated bodies\" were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling \"Luse bodies\" in 7 cases. These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms. These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made.", "contents": "Extraocular muscles: light microscopy and ultrastructural features. Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One mum thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2--3 mum sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres. Ultrastructural features consisted of vacuoles within myofilament bundles, \"smearing\" of Z bands, and \"nemaline rods\". Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. \"Leptomeric\" profiles, \"Zebra bodies\", or \"striated bodies\" were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling \"Luse bodies\" in 7 cases. These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms. These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made."} {"id": "PMID:178146", "title": "Smooth-muscle antibodies and antibodies to cytomegalovirus and Epstein-Barr virus in leukaemias and lymphomata.", "content": "By means of the indirect immunofluorescent method, smooth-muscle antibodies (SMA) were detected significantly more often in patients with malignant diseases (11.7%) than in normal controls (3.3%) (0.02 greater than pgreater than 0.01). SMA occurred in 23.8% of patients with Hodgkin's disease, in 13.3% of patients with myeloproliferative diseases and in 4.7% of patients with lymphoproliferative diseases. Other tissue antibodies were rare and they were found to occur at the same frequency in patients and controls. The occurrence of cytomegalovirus (CMV) antibodies did not differ significantly in patients and controls and, in both groups, the frequency of these antibodies increased with increasing age. The frequency of Epstein-Barr-virus (EBV) antibodies increased also with increasing age both in patients and controls, but these antibodies were found more frequently in patients than in controls (p=0.03). No relationship between the occurrence of SMA and viral antibodies was demonstrated. Thus, the development of SMA in patients with malignancies could not be shown to be due to CMV or EBV infection.", "contents": "Smooth-muscle antibodies and antibodies to cytomegalovirus and Epstein-Barr virus in leukaemias and lymphomata. By means of the indirect immunofluorescent method, smooth-muscle antibodies (SMA) were detected significantly more often in patients with malignant diseases (11.7%) than in normal controls (3.3%) (0.02 greater than pgreater than 0.01). SMA occurred in 23.8% of patients with Hodgkin's disease, in 13.3% of patients with myeloproliferative diseases and in 4.7% of patients with lymphoproliferative diseases. Other tissue antibodies were rare and they were found to occur at the same frequency in patients and controls. The occurrence of cytomegalovirus (CMV) antibodies did not differ significantly in patients and controls and, in both groups, the frequency of these antibodies increased with increasing age. The frequency of Epstein-Barr-virus (EBV) antibodies increased also with increasing age both in patients and controls, but these antibodies were found more frequently in patients than in controls (p=0.03). No relationship between the occurrence of SMA and viral antibodies was demonstrated. Thus, the development of SMA in patients with malignancies could not be shown to be due to CMV or EBV infection."} {"id": "PMID:178149", "title": "Hepatography with intravenously injected emulsified iodolipids. Preliminary results.", "content": "Hepatography by slow intravenous infusion of AG 60 99 Guerbet (iodized lipids in a stable emulsion) was performed in 31 patients, aged 17 to 77 years, to detect circumscribed hepatic lesions: metastases, cysts, and hepatic abscesses. The tolerance was good with minor side effects unrelated to the patient's age. The uptake of the medium involves the entire liver and lasts for several hours, allowing tomography to be carried out. Intrahepatic lesions with a diameter of less than one centimeter may be demonstrated. Hepatography proves to be the most accurate method available at present for exploration of the liver.", "contents": "Hepatography with intravenously injected emulsified iodolipids. Preliminary results. Hepatography by slow intravenous infusion of AG 60 99 Guerbet (iodized lipids in a stable emulsion) was performed in 31 patients, aged 17 to 77 years, to detect circumscribed hepatic lesions: metastases, cysts, and hepatic abscesses. The tolerance was good with minor side effects unrelated to the patient's age. The uptake of the medium involves the entire liver and lasts for several hours, allowing tomography to be carried out. Intrahepatic lesions with a diameter of less than one centimeter may be demonstrated. Hepatography proves to be the most accurate method available at present for exploration of the liver."} {"id": "PMID:178150", "title": "Hepatosplenography by intravenous injection of a new iodized oily emulsion.", "content": "Hepatosplenography with intravenously injected iodized lipid emulsion has been performed in 30 cases and the results reported. The side effects were minor and transient, as the elimination is rapid. The uptake in the liver was satisfactory and permitted tomography both of the liver and the spleen. Small neoplasms and splenic nodules in Hodgkin's disease could be detected and located accurately.", "contents": "Hepatosplenography by intravenous injection of a new iodized oily emulsion. Hepatosplenography with intravenously injected iodized lipid emulsion has been performed in 30 cases and the results reported. The side effects were minor and transient, as the elimination is rapid. The uptake in the liver was satisfactory and permitted tomography both of the liver and the spleen. Small neoplasms and splenic nodules in Hodgkin's disease could be detected and located accurately."} {"id": "PMID:178145", "title": "[Changes in area of mucous membrane in otosclerosis].", "content": "In 98 samples of middle-ear mucosa, taken from patients during otosclerotic stapes surgery, considerable pathological changes in the organization of the capillaries were found (endothelial hydrops, proliferation of the intima and adventitia, total obliteration of small vessels). They caused pathological reactions of the mesenchymal elements of the submucosa: fibrocytes undergo lysis, collagen fibres show fibolysis and hyalinosis. Free and cellular bound calcium deposits are located in these lytic areas. Even the epithelial stratum reveals uncommon inclusions such as glycogen and acid mucopolysaccharides. The basement membranes of the capillaries as well as of the epithelium show enlargements and solution of their ultrastructure. The changes of the connective tissue and of the epithelium are secondary to the capillary obstructions.", "contents": "[Changes in area of mucous membrane in otosclerosis]. In 98 samples of middle-ear mucosa, taken from patients during otosclerotic stapes surgery, considerable pathological changes in the organization of the capillaries were found (endothelial hydrops, proliferation of the intima and adventitia, total obliteration of small vessels). They caused pathological reactions of the mesenchymal elements of the submucosa: fibrocytes undergo lysis, collagen fibres show fibolysis and hyalinosis. Free and cellular bound calcium deposits are located in these lytic areas. Even the epithelial stratum reveals uncommon inclusions such as glycogen and acid mucopolysaccharides. The basement membranes of the capillaries as well as of the epithelium show enlargements and solution of their ultrastructure. The changes of the connective tissue and of the epithelium are secondary to the capillary obstructions."} {"id": "PMID:178151", "title": "Treatment of glioblastoma multiforme. A review.", "content": "Experience in irradiating 114 patients with glioblastoma multiforme is reviewed. The split-course therapy utilized in this series, even to high doses (approximately 5 600 rad in 20 fractions over 45 to 50 days), was not associated with an improved survival and does not seem of benefit over conventional fractionation. Adding BCNU (or perhaps tri-iodothyronine) to medium field (less than 135 mc) and moderate dose irradiation (5 000 rad in 25 treatments in 33 days) may improve the outlook for patients with glioblastoma multiforme. An expanded controlled clinical trial to assess this promise of improved treatment results seems indicated.", "contents": "Treatment of glioblastoma multiforme. A review. Experience in irradiating 114 patients with glioblastoma multiforme is reviewed. The split-course therapy utilized in this series, even to high doses (approximately 5 600 rad in 20 fractions over 45 to 50 days), was not associated with an improved survival and does not seem of benefit over conventional fractionation. Adding BCNU (or perhaps tri-iodothyronine) to medium field (less than 135 mc) and moderate dose irradiation (5 000 rad in 25 treatments in 33 days) may improve the outlook for patients with glioblastoma multiforme. An expanded controlled clinical trial to assess this promise of improved treatment results seems indicated."} {"id": "PMID:178157", "title": "The pathophysiology of sleep disorders in pediatrics. Part I. Sleep in infancy.", "content": "In this part of the chapter we have described the characteristics of two alternating sleep states - REM and NREM sleep in preterm and full-term infants. We have indicated how individual physiologic measures, recorded during sleep, mature and become synchromized into patterns that define the sleep states. We have described abnormalities in this process and have related them to clinical populations of deviant infants. Throughout, we have emphasized the complexity of the process and the methodologic sophistication required to investigate adequately the multiple dimensions of sleep. Despite somewhat discrepant and confusing reports in the literature, we continue to believe that sleep studies will provide rewarding insights into the central nervous system functioning of the developing young infant.", "contents": "The pathophysiology of sleep disorders in pediatrics. Part I. Sleep in infancy. In this part of the chapter we have described the characteristics of two alternating sleep states - REM and NREM sleep in preterm and full-term infants. We have indicated how individual physiologic measures, recorded during sleep, mature and become synchromized into patterns that define the sleep states. We have described abnormalities in this process and have related them to clinical populations of deviant infants. Throughout, we have emphasized the complexity of the process and the methodologic sophistication required to investigate adequately the multiple dimensions of sleep. Despite somewhat discrepant and confusing reports in the literature, we continue to believe that sleep studies will provide rewarding insights into the central nervous system functioning of the developing young infant."} {"id": "PMID:178159", "title": "Lactic acidosis in childhood.", "content": "Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an \"idiopathic\" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders.", "contents": "Lactic acidosis in childhood. Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an \"idiopathic\" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders."} {"id": "PMID:178164", "title": "Improved detection of myocardial infarction with technetium-99m stannous pyrophosphate and serum MB creatine phosphokinase.", "content": "The relative sensitivity and combined value of myocardial technetium-99m stannous pyrophosphate imaging and determinations of serum MB creatine phosphokinase (the \"myocardial\" CPK isoenzyme) in detecting acute myocardial infarction were evaluated in 41 patients with suspected infarction and 23 patients recovering from cardiac surgery. In the patients with suspected infarction, myocardial infarction was confirmed in 25 and was consistently associated with increased serum MB CPK. Abnormal radionuclide images were obtained in 23 of 25 patients (92 percent) with definite myocardial infarction and in 2 of 16 patients without confirmed infarction. Although the localization of infarction by imaging correlated well with the localization by electrocardiogram, infarct size estimated by imaging did not correlate well with estimates based on peak total serum CPK activity or serial changes in CPK activity. Serum MB CPK activity increased after cardiac surgery in 6 patients undergoing valve replacement and in 17 patients undergoing coronary arterial bypass surgery. However, no patient with valve replacement and only 1 of the 17 with bypass surgery had an abnormal radionuclide image. These results suggest that (1) abnormal radionuclide images in patients without infarction can be distinguished from abnormal images indicative of ischemic necrosis by consideration of MB CPK activity and (2) interpretation of elevated MB CPK activity, particularly in particularly in patients undergoing cardiac surgery, is facilitated by evaluation with imaging.", "contents": "Improved detection of myocardial infarction with technetium-99m stannous pyrophosphate and serum MB creatine phosphokinase. The relative sensitivity and combined value of myocardial technetium-99m stannous pyrophosphate imaging and determinations of serum MB creatine phosphokinase (the \"myocardial\" CPK isoenzyme) in detecting acute myocardial infarction were evaluated in 41 patients with suspected infarction and 23 patients recovering from cardiac surgery. In the patients with suspected infarction, myocardial infarction was confirmed in 25 and was consistently associated with increased serum MB CPK. Abnormal radionuclide images were obtained in 23 of 25 patients (92 percent) with definite myocardial infarction and in 2 of 16 patients without confirmed infarction. Although the localization of infarction by imaging correlated well with the localization by electrocardiogram, infarct size estimated by imaging did not correlate well with estimates based on peak total serum CPK activity or serial changes in CPK activity. Serum MB CPK activity increased after cardiac surgery in 6 patients undergoing valve replacement and in 17 patients undergoing coronary arterial bypass surgery. However, no patient with valve replacement and only 1 of the 17 with bypass surgery had an abnormal radionuclide image. These results suggest that (1) abnormal radionuclide images in patients without infarction can be distinguished from abnormal images indicative of ischemic necrosis by consideration of MB CPK activity and (2) interpretation of elevated MB CPK activity, particularly in particularly in patients undergoing cardiac surgery, is facilitated by evaluation with imaging."} {"id": "PMID:178165", "title": "A comparative morphometric analysis of the effects of thyroxine and ACTH on the zona fasciculata of rat adrenal cortex.", "content": "The effects of thyroxine and ACTH on the ultrastructure of cells of the adrenal zona fasciculata were studied by morphometric analysis and compared by two-way analysis of variance. The results indicate that the effects of thyroxine and ACTH are different and independent. The statistically significant differences in effect of thyroxine and ACTH are: thyroxine causes an increase in the volume fraction of mitochondria and a decrease in the volume fraction of endoplasmic reticulum independent of ACTH; thyroxine causes a decrease in surface density of mitochondria and endoplasmic reticulum in the absence of ACTH, but in the presence of ACTH this effect is moderated by an interaction of throxine and ACTH. There were no statistically significant effects of either thyroxine or ACTH on volume fraction or surface density of liposomes.", "contents": "A comparative morphometric analysis of the effects of thyroxine and ACTH on the zona fasciculata of rat adrenal cortex. The effects of thyroxine and ACTH on the ultrastructure of cells of the adrenal zona fasciculata were studied by morphometric analysis and compared by two-way analysis of variance. The results indicate that the effects of thyroxine and ACTH are different and independent. The statistically significant differences in effect of thyroxine and ACTH are: thyroxine causes an increase in the volume fraction of mitochondria and a decrease in the volume fraction of endoplasmic reticulum independent of ACTH; thyroxine causes a decrease in surface density of mitochondria and endoplasmic reticulum in the absence of ACTH, but in the presence of ACTH this effect is moderated by an interaction of throxine and ACTH. There were no statistically significant effects of either thyroxine or ACTH on volume fraction or surface density of liposomes."} {"id": "PMID:178167", "title": "Postprandial plasma triglyceride and cholesterol responses to a low-fat meal.", "content": "Postprandial plasma cholesterol and triglyceride (TG) levels were measured after the consumption of a relatively low-fat (35% of calories) diet in 41 subjects. Plasma cholesterol levels did not change appreciably during the postprandial state. In 34 subjects a biphasic plasma TG response curve was noted, with an initial peak occurring 1 to 3 hr after feeding and a secondary TG peak 4 to 7 hr after the meal. The primary peak was greater than 90%, accounted for by chylomicrons, whereas the secondary peak represented very low-density lipoproteins (greater than 82%). Furthermore, the heights of the primary and secondary peaks were closely correlated to the fasting TG level (r = 0.61 and 0.72, respectively) indicating that the fasting TG concentration is an important determinant of the postprandial TG response. Because low-fat (high-carbohydrate) diets are known to raise fasting TG levels in patients who do not have fasting hyperchylomicronemia, and because relatively few patients have chylomicrons in the fasting state, these data suggest that such diets may lead to day long increases in plasma TG levels in the majority of subjects.", "contents": "Postprandial plasma triglyceride and cholesterol responses to a low-fat meal. Postprandial plasma cholesterol and triglyceride (TG) levels were measured after the consumption of a relatively low-fat (35% of calories) diet in 41 subjects. Plasma cholesterol levels did not change appreciably during the postprandial state. In 34 subjects a biphasic plasma TG response curve was noted, with an initial peak occurring 1 to 3 hr after feeding and a secondary TG peak 4 to 7 hr after the meal. The primary peak was greater than 90%, accounted for by chylomicrons, whereas the secondary peak represented very low-density lipoproteins (greater than 82%). Furthermore, the heights of the primary and secondary peaks were closely correlated to the fasting TG level (r = 0.61 and 0.72, respectively) indicating that the fasting TG concentration is an important determinant of the postprandial TG response. Because low-fat (high-carbohydrate) diets are known to raise fasting TG levels in patients who do not have fasting hyperchylomicronemia, and because relatively few patients have chylomicrons in the fasting state, these data suggest that such diets may lead to day long increases in plasma TG levels in the majority of subjects."} {"id": "PMID:178168", "title": "Anorexia-producing intermediary metabolites.", "content": "Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells.", "contents": "Anorexia-producing intermediary metabolites. Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells."} {"id": "PMID:178169", "title": "Additive risk factors in atherosclerosis.", "content": "The tissues of human subjects assayed for a higher level of vitamin D than the tissues of 6-month-old swine which had been fed a commercial ration containing 14 times more vitamin D3 than the National Research Council recommended requirement for growing swine. Bioassays of commercial livestock feeds indicate much higher vitamin D contents than the National Research Council recommendation. High levels of vitamin D activity are demonstrable in tissues from the animals on such livestock feeds. The grossly normal areas of the aorta of weanling swine fed 100,000 IU of vitamin D3/pound of basal ration during the initial 6 weeks had a higher frequency of degenerated smooth muscle cells than the grossly normal areas of the aorta of swine fed the commercial ration, or 7.43+/-0.45 and 5.60+/-0.27/100 cells, respectively, at the age of 3 months. Tbe addition of 13 pounds of hydrogenated fat and 200 g of cholesterol/100 pounds of the commercial ration further increased the frequency of degenerated smooth muscle cells by 0.53 (P less than 0.05) or to 7.96 +/- 0.39/100 cells in the grossly normal areas of the aorta of weanling swine fed this fat-supplemented ration to 3 months of age.", "contents": "Additive risk factors in atherosclerosis. The tissues of human subjects assayed for a higher level of vitamin D than the tissues of 6-month-old swine which had been fed a commercial ration containing 14 times more vitamin D3 than the National Research Council recommended requirement for growing swine. Bioassays of commercial livestock feeds indicate much higher vitamin D contents than the National Research Council recommendation. High levels of vitamin D activity are demonstrable in tissues from the animals on such livestock feeds. The grossly normal areas of the aorta of weanling swine fed 100,000 IU of vitamin D3/pound of basal ration during the initial 6 weeks had a higher frequency of degenerated smooth muscle cells than the grossly normal areas of the aorta of swine fed the commercial ration, or 7.43+/-0.45 and 5.60+/-0.27/100 cells, respectively, at the age of 3 months. Tbe addition of 13 pounds of hydrogenated fat and 200 g of cholesterol/100 pounds of the commercial ration further increased the frequency of degenerated smooth muscle cells by 0.53 (P less than 0.05) or to 7.96 +/- 0.39/100 cells in the grossly normal areas of the aorta of weanling swine fed this fat-supplemented ration to 3 months of age."} {"id": "PMID:178170", "title": "Decreased T-lymphocytes in patients with mammary cancer.", "content": "The levels of thymus-derived lymphocytes (T-cells) in samples of peripheral blood from 47 patients with carcinoma of the breast, 36 patients with benign mammary lesions, and 33 matched normal controls were determined. Results were analyzed with three statistical tests. It was found that the mean percentages of T-lymphocytes differed significantly among the three groups of patients (p less than 0.001). The mean percentages of rosette-forming lymphocytes were 72.8 for the normal group, 60.6 for patients with benign mammary lesions, and 45.1 for the patients with carcinoma. The finding of lower levels of T-lymphocytes in the peripheral blood of individuals with mammary cancer is of particular significance since all the patients in this study were otherwise in apparently good general health and undergoing no treatment.", "contents": "Decreased T-lymphocytes in patients with mammary cancer. The levels of thymus-derived lymphocytes (T-cells) in samples of peripheral blood from 47 patients with carcinoma of the breast, 36 patients with benign mammary lesions, and 33 matched normal controls were determined. Results were analyzed with three statistical tests. It was found that the mean percentages of T-lymphocytes differed significantly among the three groups of patients (p less than 0.001). The mean percentages of rosette-forming lymphocytes were 72.8 for the normal group, 60.6 for patients with benign mammary lesions, and 45.1 for the patients with carcinoma. The finding of lower levels of T-lymphocytes in the peripheral blood of individuals with mammary cancer is of particular significance since all the patients in this study were otherwise in apparently good general health and undergoing no treatment."} {"id": "PMID:178171", "title": "Germ-cell tumors of the mediastinum, postmortem findings.", "content": "Autopsy findings in 20 cases of clinical extragonadal germ-cell tumors arising in the anterior mediastinum are presented. The histologic types were: 2 choriocarcinomas, 3 seminomas, 3 malignant teratomas, 3 embryonal carcinomas, and 9 mixed germ-cell tumors. All of the patients were men, and the ages ranged from 14 to 45 years, with a mean of 32.5 years. The mean survival for these patients after diagnosis was 10.9 months. Local recurrence was characteristic of non-seminomatous tumors. In patients with seminoma, local control of the disease was good, but distant metastases were the cause of death. The most frequent sites of metastases were lungs, bones and liver. In all 20 cases, the testes were carefully step-sectioned. Occult tumor was found in only one case of embryonal carcinoma and a well-defined testicular scar with calcification in a patient with choriocarcinoma. Both patients had lower retroperitoneal metastases. These findings support the premise that, in the majority of cases, these tumors had a primary extragonadal origin.", "contents": "Germ-cell tumors of the mediastinum, postmortem findings. Autopsy findings in 20 cases of clinical extragonadal germ-cell tumors arising in the anterior mediastinum are presented. The histologic types were: 2 choriocarcinomas, 3 seminomas, 3 malignant teratomas, 3 embryonal carcinomas, and 9 mixed germ-cell tumors. All of the patients were men, and the ages ranged from 14 to 45 years, with a mean of 32.5 years. The mean survival for these patients after diagnosis was 10.9 months. Local recurrence was characteristic of non-seminomatous tumors. In patients with seminoma, local control of the disease was good, but distant metastases were the cause of death. The most frequent sites of metastases were lungs, bones and liver. In all 20 cases, the testes were carefully step-sectioned. Occult tumor was found in only one case of embryonal carcinoma and a well-defined testicular scar with calcification in a patient with choriocarcinoma. Both patients had lower retroperitoneal metastases. These findings support the premise that, in the majority of cases, these tumors had a primary extragonadal origin."} {"id": "PMID:178172", "title": "The occurrence in a neonate of a pancreatic adenoma with nesidioblastosis in the tumor.", "content": "A newborn with persistent hypoglycemia and fixed insulin secretion unresponsive to medical management underwent 80% pancreatectomy. A 1-cm. nonencapsulated islet-cell adenoma near the tail of the pancreas was identified histologically. Islet-cell granules stained with indirect aldehyde fuchsin. Throughout the tumor, areas of nesidioblastosis were identified. The persistence of this embryologic process suggests a basic mechanism for the adenoma formation.", "contents": "The occurrence in a neonate of a pancreatic adenoma with nesidioblastosis in the tumor. A newborn with persistent hypoglycemia and fixed insulin secretion unresponsive to medical management underwent 80% pancreatectomy. A 1-cm. nonencapsulated islet-cell adenoma near the tail of the pancreas was identified histologically. Islet-cell granules stained with indirect aldehyde fuchsin. Throughout the tumor, areas of nesidioblastosis were identified. The persistence of this embryologic process suggests a basic mechanism for the adenoma formation."} {"id": "PMID:178178", "title": "Red cell uridine monophosphate kinase: effects of red cell aging on the activity of two UMPK gene products.", "content": "We have previously reported that uridine monophosphate kinase (UMPK) is genetically polymorphic in man, and that the UMPK2 gene product has less activity than that of UMPK1 when measured in normal red cells. In this paper we present evidence that the activity of UMPK, like that of many other enzymes, declines during red cell aging, and that the lower activity of UMPK 2, as compared with UMPK 1, is best explained by its more rapid catabolism.", "contents": "Red cell uridine monophosphate kinase: effects of red cell aging on the activity of two UMPK gene products. We have previously reported that uridine monophosphate kinase (UMPK) is genetically polymorphic in man, and that the UMPK2 gene product has less activity than that of UMPK1 when measured in normal red cells. In this paper we present evidence that the activity of UMPK, like that of many other enzymes, declines during red cell aging, and that the lower activity of UMPK 2, as compared with UMPK 1, is best explained by its more rapid catabolism."} {"id": "PMID:178179", "title": "Variance of plasma free and esterified cholesterol in adult twins.", "content": "Total, free and esterified cholesterol were measured in the plasma, high density lipoproteins, low density lipoproteins, and total cholesterol in the very low density lipoproteins of 141 pairs of adult white male twins. Free cholesterol in plasma, high density lipoproteins and low density lipoproteins had significant genetic variance. Esterified cholesterol had greater total variance in dizygotic than monozygotic twins, interpreted as evidence for greater environmental influences on the two types of twins. After bias due to unequal environmental effects on the two types of twins was removed, there was no significant genetic variance for any esterified fraction of cholesterol.", "contents": "Variance of plasma free and esterified cholesterol in adult twins. Total, free and esterified cholesterol were measured in the plasma, high density lipoproteins, low density lipoproteins, and total cholesterol in the very low density lipoproteins of 141 pairs of adult white male twins. Free cholesterol in plasma, high density lipoproteins and low density lipoproteins had significant genetic variance. Esterified cholesterol had greater total variance in dizygotic than monozygotic twins, interpreted as evidence for greater environmental influences on the two types of twins. After bias due to unequal environmental effects on the two types of twins was removed, there was no significant genetic variance for any esterified fraction of cholesterol."} {"id": "PMID:178181", "title": "The HCG-beta-subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen.", "content": "Antiserum generated against the hormone-specific beta-subunit of hCG uas used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When 125 I-hCGbeta served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the 125I-hCGbeta with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCGbeta suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assay aberration may result from the presence of free hCGbeta in these sera.", "contents": "The HCG-beta-subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen. Antiserum generated against the hormone-specific beta-subunit of hCG uas used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When 125 I-hCGbeta served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the 125I-hCGbeta with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCGbeta suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assay aberration may result from the presence of free hCGbeta in these sera."} {"id": "PMID:178182", "title": "Virilizing adrenocortical adenoma studied by selective adrenal venography.", "content": "A 15-year-old girl with primary amenorrhea, hirsutism, and enlargement of the clitoris was found to have an increased titer of the urinary neutral 17-ketosteroids which failed to decrease after the administration of dexamethasone and an adrenal tumor was demonstrable on venography. Analysis of the adrenal venous effluent revealed gradients on the side of the tumor for testosterone, androstenedione, estradiol, and dehydroepiandrosterone sulfate. Following removal of the tumor, the hirsutism improved markedly, the menses returned, and sexual maturation progressed.", "contents": "Virilizing adrenocortical adenoma studied by selective adrenal venography. A 15-year-old girl with primary amenorrhea, hirsutism, and enlargement of the clitoris was found to have an increased titer of the urinary neutral 17-ketosteroids which failed to decrease after the administration of dexamethasone and an adrenal tumor was demonstrable on venography. Analysis of the adrenal venous effluent revealed gradients on the side of the tumor for testosterone, androstenedione, estradiol, and dehydroepiandrosterone sulfate. Following removal of the tumor, the hirsutism improved markedly, the menses returned, and sexual maturation progressed."} {"id": "PMID:178183", "title": "Failure of systemically administered adenine arabinoside to affect humoral and cell-mediated immunity.", "content": "The effect of a high dosage (250 mg/kg of body weight) of adenine arabinoside or ara-A (9-beta-D-arabinofuranosyladenine) on humoral immunity was studied in New Zealand white rabbits infected with the McKrae strain of herpes simplex virus. The rabbits were treated daily for 14 days with subcutaneous injections of ara-A. The primary and secondary humoral responses, as measured by neutralizing antibody titers, developed similarly in control and treated groups. Similar drug treatment was used on guinea pigs before or after sensitization with BCG vaccine. Subsequent challenge of the sensitized animals with Old tuberculin solution indicated that ara-A treatment had no effect on the induction or previously established cell-mediated immunity. The lack of immunosuppressive activity of ara-A at dosage levels higher than those used in primates makes this drug a potentially effective agent in the systemic treatment of herpetic infections.", "contents": "Failure of systemically administered adenine arabinoside to affect humoral and cell-mediated immunity. The effect of a high dosage (250 mg/kg of body weight) of adenine arabinoside or ara-A (9-beta-D-arabinofuranosyladenine) on humoral immunity was studied in New Zealand white rabbits infected with the McKrae strain of herpes simplex virus. The rabbits were treated daily for 14 days with subcutaneous injections of ara-A. The primary and secondary humoral responses, as measured by neutralizing antibody titers, developed similarly in control and treated groups. Similar drug treatment was used on guinea pigs before or after sensitization with BCG vaccine. Subsequent challenge of the sensitized animals with Old tuberculin solution indicated that ara-A treatment had no effect on the induction or previously established cell-mediated immunity. The lack of immunosuppressive activity of ara-A at dosage levels higher than those used in primates makes this drug a potentially effective agent in the systemic treatment of herpetic infections."} {"id": "PMID:178184", "title": "Ultrastructure and formation of lamellated inclusion bodies in induced lung tumors of the European hamster.", "content": "Utlrastructure and formation of lamellated inclusion bodies (LB) in N-dibutyl-nitrosamine-induced lung tumors in European hamsters are described. Two types of LBs are observed: one with cross-barred lamellae and one with concentric lamellae. Both types develop from lysosome-like dense bodies which are formed by the Golgi apparatus. More mature forms fuse with rough endoplasmic reticulum (RER). Mature LBs migrate to the cell surface, where their contents are extruded into the alveolar lumen by means of a merocrine secretion. The extruded lamellae give rise to the myelin figures and lattices that are reported to possess surfactant properties.", "contents": "Ultrastructure and formation of lamellated inclusion bodies in induced lung tumors of the European hamster. Utlrastructure and formation of lamellated inclusion bodies (LB) in N-dibutyl-nitrosamine-induced lung tumors in European hamsters are described. Two types of LBs are observed: one with cross-barred lamellae and one with concentric lamellae. Both types develop from lysosome-like dense bodies which are formed by the Golgi apparatus. More mature forms fuse with rough endoplasmic reticulum (RER). Mature LBs migrate to the cell surface, where their contents are extruded into the alveolar lumen by means of a merocrine secretion. The extruded lamellae give rise to the myelin figures and lattices that are reported to possess surfactant properties."} {"id": "PMID:178180", "title": "Effects of glucocorticoids on carbohydrate metabolism.", "content": "A patient with pre-existing diabetes mellitus who was receiving corticosteroids in an effort to prevent transplant rejection was presented. The patient's hyperglycemia was exacerbated by the corticosteroids, and the discussion centered around this aspect of the case. The clinical effects of glucocorticoids on carbohydrate metabolism were reviewed, and four general points were made: (1) the chronic effects of corticoids on glucose tolerance are much less pronounced than the acute effects; (2) the degree of impariment is proportional to the pre-existing status of glucose tolerance; (3) development of frank diabetes mellitus in a previously normal patient is unusual; and (4) the abnormalities of carbohydrate metabolism induced by glucocorticoids fit the pattern of an insulin resistant state. The subject was reviewed and relevant in vivo and in vitro observations were presented in support of the above concepts, and to help identify the pathophysiologic mechanisms involved. It was postulated that glucocorticoids affect glucose metabolism by decreasing glucose utilization and by increasing hepatic glucose production. The possible mechanisms underlying these effects were discussed.", "contents": "Effects of glucocorticoids on carbohydrate metabolism. A patient with pre-existing diabetes mellitus who was receiving corticosteroids in an effort to prevent transplant rejection was presented. The patient's hyperglycemia was exacerbated by the corticosteroids, and the discussion centered around this aspect of the case. The clinical effects of glucocorticoids on carbohydrate metabolism were reviewed, and four general points were made: (1) the chronic effects of corticoids on glucose tolerance are much less pronounced than the acute effects; (2) the degree of impariment is proportional to the pre-existing status of glucose tolerance; (3) development of frank diabetes mellitus in a previously normal patient is unusual; and (4) the abnormalities of carbohydrate metabolism induced by glucocorticoids fit the pattern of an insulin resistant state. The subject was reviewed and relevant in vivo and in vitro observations were presented in support of the above concepts, and to help identify the pathophysiologic mechanisms involved. It was postulated that glucocorticoids affect glucose metabolism by decreasing glucose utilization and by increasing hepatic glucose production. The possible mechanisms underlying these effects were discussed."} {"id": "PMID:178185", "title": "The occurrence and frequency of type C virus-like particles in placentas from patients with systemic lupus erythematosus and from normal subjects.", "content": "Type C RNA virus-like particles were found by electron microscopy in term placentas from 3 patients with systemic lupus erythematosus (SLE), 1 with probable SLE, and 2 normal patients. The virus-like particles were mainly of a budding or immature type located at or near the cell membrane of syncytiotrophoblasts in chorionic villi. Type C virus-like particles were not observed in the term placenta from a patient with chronic discoid LE, nor in early gestation specimens from 1 normal patient and 4 patients with SLE. The frequency of the Type C particles varied greatly: They were readily found in the patient with probable SLE, and only here were groups of budding particles observed. Type C particles were less numerous in one normal placenta and rare in the other positive placentas, both SLE and normal. Heretofore undescribed crystalline inclusions were found in the cytoplasm of chorionic villous endothelial cells from 3 patients with SLE and 1 with discoid LE. Tubuloreticular structures were observed in the maternal endometrium of 1 patient with SLE.", "contents": "The occurrence and frequency of type C virus-like particles in placentas from patients with systemic lupus erythematosus and from normal subjects. Type C RNA virus-like particles were found by electron microscopy in term placentas from 3 patients with systemic lupus erythematosus (SLE), 1 with probable SLE, and 2 normal patients. The virus-like particles were mainly of a budding or immature type located at or near the cell membrane of syncytiotrophoblasts in chorionic villi. Type C virus-like particles were not observed in the term placenta from a patient with chronic discoid LE, nor in early gestation specimens from 1 normal patient and 4 patients with SLE. The frequency of the Type C particles varied greatly: They were readily found in the patient with probable SLE, and only here were groups of budding particles observed. Type C particles were less numerous in one normal placenta and rare in the other positive placentas, both SLE and normal. Heretofore undescribed crystalline inclusions were found in the cytoplasm of chorionic villous endothelial cells from 3 patients with SLE and 1 with discoid LE. Tubuloreticular structures were observed in the maternal endometrium of 1 patient with SLE."} {"id": "PMID:178188", "title": "Primate kidney function in hemorrhagic shock as influenced by dibutyryl cyclic AMP.", "content": "Standardized hemorrhagic shock was employed to study alterations in electrolyte and water handling in the owl monkey, either normally hydrated or moderately dehydrated. Increase in fractional clearance of osmolarity,sodium, and calcium occurred with retransfusion after the hypotensive phase. In the hydrated animals, free-water clearance became positive, and the urine-to-plasma osmolarity ratio [(U/P)osM] decreased below 1.0. In the dehydrated animals, free-water reabsorption (TCH2O) decreased but remained negative,while (U/P)osM remained above 1.0. Dibutyryl cyclic AMP (DBcAMP) was infused into the renal arterial supply in an attempt to correct a possible deficiency of cyclic AMP production. In the hydrated group, free-water clearance (CH2O) became more positive with infusion, and (U/P)osM decreased even further, with no effect on fractional sodium clearance. Effects were less or absent in the dehydrated group. Possible explanations for the observed effects of DBcAMP are considered. It was concluded that the loss of concentrating power seen in hemorrhagic shock occurs at a step beyond the production of cyclic AMP by adenylate cyclase.", "contents": "Primate kidney function in hemorrhagic shock as influenced by dibutyryl cyclic AMP. Standardized hemorrhagic shock was employed to study alterations in electrolyte and water handling in the owl monkey, either normally hydrated or moderately dehydrated. Increase in fractional clearance of osmolarity,sodium, and calcium occurred with retransfusion after the hypotensive phase. In the hydrated animals, free-water clearance became positive, and the urine-to-plasma osmolarity ratio [(U/P)osM] decreased below 1.0. In the dehydrated animals, free-water reabsorption (TCH2O) decreased but remained negative,while (U/P)osM remained above 1.0. Dibutyryl cyclic AMP (DBcAMP) was infused into the renal arterial supply in an attempt to correct a possible deficiency of cyclic AMP production. In the hydrated group, free-water clearance (CH2O) became more positive with infusion, and (U/P)osM decreased even further, with no effect on fractional sodium clearance. Effects were less or absent in the dehydrated group. Possible explanations for the observed effects of DBcAMP are considered. It was concluded that the loss of concentrating power seen in hemorrhagic shock occurs at a step beyond the production of cyclic AMP by adenylate cyclase."} {"id": "PMID:178189", "title": "Muscle fiber involvement during training of different intensities and durations.", "content": "The extent of skeletal muscle fiber type involvement during exercise training was evaluated by assessing the increase in oxidative markers in the muscles of rats trained by various exercise programs. Rats were trained by running 6 days/wk at 1 mph for 12 wk by one of four protocols: group I-10% grade, 2 h/day; group II-10% grade, 4 h/day; group III-30% grade, 40 min/day; and group IV-30% grade, 2 h/day. No distinction was found between the different programs for the increase in cytochrome c content or citrate synthase (CS) activity of mixed muscle. The more intense programs utilizing a 30% grade induced an increase in CS activity in the fast-twitch white (FTW) fiber that was twice that found in the 10% grade groups. The fast-twitch red (FTR) fibers of the 2 h/day or more groups showed a similar increase (90-95%) in CS activity except for the group that ran for only 40 min/day. These data suggest that: 1) running durations of moderately intense exercise longer than 2 h/day do not further increase the oxidative capacity of the working muscles; and 2) more intense exercise builds on the performance of previously used FTR fibers and additionally involves the low oxidative FTW fibers.", "contents": "Muscle fiber involvement during training of different intensities and durations. The extent of skeletal muscle fiber type involvement during exercise training was evaluated by assessing the increase in oxidative markers in the muscles of rats trained by various exercise programs. Rats were trained by running 6 days/wk at 1 mph for 12 wk by one of four protocols: group I-10% grade, 2 h/day; group II-10% grade, 4 h/day; group III-30% grade, 40 min/day; and group IV-30% grade, 2 h/day. No distinction was found between the different programs for the increase in cytochrome c content or citrate synthase (CS) activity of mixed muscle. The more intense programs utilizing a 30% grade induced an increase in CS activity in the fast-twitch white (FTW) fiber that was twice that found in the 10% grade groups. The fast-twitch red (FTR) fibers of the 2 h/day or more groups showed a similar increase (90-95%) in CS activity except for the group that ran for only 40 min/day. These data suggest that: 1) running durations of moderately intense exercise longer than 2 h/day do not further increase the oxidative capacity of the working muscles; and 2) more intense exercise builds on the performance of previously used FTR fibers and additionally involves the low oxidative FTW fibers."} {"id": "PMID:178190", "title": "Short versus long hospitalization: a propspective controlled study. IV. One-year follow-up results for schizophrenie patients.", "content": "The authors compared treatment results for 141 schizophrenic patients randomly assigned to short-term or long-term hospitalization. Test results indicated that the long-term group was functioning significantly better one year after admission according to global measures only. The authors caution that the differences between the two groups, although statistically reliable, were modest and may have been confounded by the amount of psychotherapy the patients received after hospitalization. Although there appears to be a general advantage to the long-term approach, further work will be needed to identify patient subgroups for whom this more expensive treatment is cost effective.", "contents": "Short versus long hospitalization: a propspective controlled study. IV. One-year follow-up results for schizophrenie patients. The authors compared treatment results for 141 schizophrenic patients randomly assigned to short-term or long-term hospitalization. Test results indicated that the long-term group was functioning significantly better one year after admission according to global measures only. The authors caution that the differences between the two groups, although statistically reliable, were modest and may have been confounded by the amount of psychotherapy the patients received after hospitalization. Although there appears to be a general advantage to the long-term approach, further work will be needed to identify patient subgroups for whom this more expensive treatment is cost effective."} {"id": "PMID:178191", "title": "Limitations of Brief Hospital Treatment.", "content": "A total of 175 newly admitted inpatients who lived with their families were randomly assigned to three treatment groups: standard inpatient care and brief hospitalization with and without transitional day care. Case reports of 6 of the 9 patients considered \"study failures\" illustrate that effective postdischarge adaptation is limited by the patients' degree of impairment as well as the family and community capacity to accept them. Although rapid return to the community is beneficial to many patients, rigid adherence to this policy is neither wise nor clinically effective.", "contents": "Limitations of Brief Hospital Treatment. A total of 175 newly admitted inpatients who lived with their families were randomly assigned to three treatment groups: standard inpatient care and brief hospitalization with and without transitional day care. Case reports of 6 of the 9 patients considered \"study failures\" illustrate that effective postdischarge adaptation is limited by the patients' degree of impairment as well as the family and community capacity to accept them. Although rapid return to the community is beneficial to many patients, rigid adherence to this policy is neither wise nor clinically effective."} {"id": "PMID:178193", "title": "Radiation therapy for testicular tumors metastasizing to the lungs.", "content": "Records of 63 cases of testicular tumors treated at the Hunter Radiation Therapy Center, Yale-New Haven Hospital from 1962 through 1971 were reviewed. One hundred percent cure rate was obtained in the 36 Stage I and II pure seminoma (Group I) patients. For Stage I, the para-aortic and homolateral iliac lymph nodes were irradiated to a dose of 3,000 to 3,500 rads in three to four weeks. Elective irradiation of the mediastinum and supraclavicular areas was omitted. For Stage II, such extended field irradiation was employed to a dose of 2,000 to 3,000 rads in two to three weeks. Six (or 43 percent) of the 14 embryonal carcinoma (Group II) patients are alive for a minimum of three to a maximum of eleven years. Both teratoma (Group III) patients are alive at five and seven years as well. All eight Stage I teratocarconoma (Group IV) patients are alive with no evident disease at three to ten years. Our data indicate the difference in prognosis between patients who subsequently developed localized lung metastases and those who initially presented with pulmonary disease. We conclude that intensive combined efforts of both radiation and medical oncologists can salvage a considerable number of patients with metachronous onset of pulmonary metastases.", "contents": "Radiation therapy for testicular tumors metastasizing to the lungs. Records of 63 cases of testicular tumors treated at the Hunter Radiation Therapy Center, Yale-New Haven Hospital from 1962 through 1971 were reviewed. One hundred percent cure rate was obtained in the 36 Stage I and II pure seminoma (Group I) patients. For Stage I, the para-aortic and homolateral iliac lymph nodes were irradiated to a dose of 3,000 to 3,500 rads in three to four weeks. Elective irradiation of the mediastinum and supraclavicular areas was omitted. For Stage II, such extended field irradiation was employed to a dose of 2,000 to 3,000 rads in two to three weeks. Six (or 43 percent) of the 14 embryonal carcinoma (Group II) patients are alive for a minimum of three to a maximum of eleven years. Both teratoma (Group III) patients are alive at five and seven years as well. All eight Stage I teratocarconoma (Group IV) patients are alive with no evident disease at three to ten years. Our data indicate the difference in prognosis between patients who subsequently developed localized lung metastases and those who initially presented with pulmonary disease. We conclude that intensive combined efforts of both radiation and medical oncologists can salvage a considerable number of patients with metachronous onset of pulmonary metastases."} {"id": "PMID:178194", "title": "Radiation therapy in the treatment of glioblastoma.", "content": "A retrospective study of 127 cases irradiated for glioblastoma was made to assess the role of radiation therapy and to determine the optimal technique of radiation therapy. The over-all survival rates of our series were 52 percent at one year, 19 percent at three years, and twelve percent at five years after radiation therapy. Survival time of the patients is influenced by various factors other than treatment: age, sex, histologic grading, duration of symptoms, and location of tumor. Among these factors, the location of the tumor was the most important in our present series. Surgical treatment can extend the survival time. More extensive resection results in longer survival, provided that the location of the tumor allows such a surgical procedure. Radiation therapy can prolong the survival time of those with glioblastoma, but a high tumor dose of more than 6,000 rads or 1,700 rets is necessary to improve the prognosis significantly. Therefore, irradiation should be administered through generous fields according to the extent of the tumor under precise planning to determine the accurate localization and extent of the tumor.", "contents": "Radiation therapy in the treatment of glioblastoma. A retrospective study of 127 cases irradiated for glioblastoma was made to assess the role of radiation therapy and to determine the optimal technique of radiation therapy. The over-all survival rates of our series were 52 percent at one year, 19 percent at three years, and twelve percent at five years after radiation therapy. Survival time of the patients is influenced by various factors other than treatment: age, sex, histologic grading, duration of symptoms, and location of tumor. Among these factors, the location of the tumor was the most important in our present series. Surgical treatment can extend the survival time. More extensive resection results in longer survival, provided that the location of the tumor allows such a surgical procedure. Radiation therapy can prolong the survival time of those with glioblastoma, but a high tumor dose of more than 6,000 rads or 1,700 rets is necessary to improve the prognosis significantly. Therefore, irradiation should be administered through generous fields according to the extent of the tumor under precise planning to determine the accurate localization and extent of the tumor."} {"id": "PMID:178195", "title": "Growth analysis of pulmonary metastases from salivary gland tumors.", "content": "Three cases of primary salivary gland tumors with lung metastasis are presented with extremely long survival (six, ten, and twelve years). The tumor doubling time was calculated and the growth rate of the pulmonary metastasis was found to be slow and erratic. A simplified table was devised, which permits rapid calculation of the tumor doubling time without the use of graphs. The presence of lung metastasis from some primary malignant salivary tumor is not necessarily an ominous sign: a long survival without symtoms is possible.", "contents": "Growth analysis of pulmonary metastases from salivary gland tumors. Three cases of primary salivary gland tumors with lung metastasis are presented with extremely long survival (six, ten, and twelve years). The tumor doubling time was calculated and the growth rate of the pulmonary metastasis was found to be slow and erratic. A simplified table was devised, which permits rapid calculation of the tumor doubling time without the use of graphs. The presence of lung metastasis from some primary malignant salivary tumor is not necessarily an ominous sign: a long survival without symtoms is possible."} {"id": "PMID:178196", "title": "Concepts for treatment of micrometastases developed in murine systems.", "content": "Small tumor cell foci, whether left in situ during primary surgical excision or escaping lethal radiation damage, as well as distant metastases, are the primary reason for treatment failure in man and are the proper targets for the chemotherapist and immunotherapist. Since cure probably requires reduction of the total body burden of tumor cells to very small numbers (possibly to less than one cell), and since first-order kinetics of tumor cell kill by drugs appears to be a natural law in cancer chemotherapy, drug treatment should be started as soon as possible after likely noncurative primary treatment with surgery or radiation. Current knowledge of tumor cell population growth kinetics indicates that the growth fraction (viable tumor cells undergoing active cell replication) is inversely related to population size. Tumor cells in micrometastases should, therefore, be more sensitive to anticancer drugs active against anabolizing cells than are tumor cells in the larger, grossly apparent primary tumor from which they were derived. This indicates the probability that micrometastases will be effectively responsive to more drugs than is the primary and clinically apparent tumor from which they came. Studies with at least four metastatic and uniformly fatal murine solid tumors (lung, breast, colon, and melanoma) have demonstrated significantly improved cure rates with drug treatment following surgical removal of the grossly apparent primary tumor than can be obtained with either surgery or drug treatment when used alone. Further, both disease staging and drug dosage have been shown to influence cure rates of combined-modality treatment. With several mouse tumors, a significantly smaller number of viable tumor cells can establish lethal tumors in the presence of radiation-inactivated tumor cells than in their absence. This suggests that small numbers of residual viable tumor cells in radiation-treated tumor sites may be a greater threat to clinical cure than smaller tumor cell populations remaining in situ after surgery.", "contents": "Concepts for treatment of micrometastases developed in murine systems. Small tumor cell foci, whether left in situ during primary surgical excision or escaping lethal radiation damage, as well as distant metastases, are the primary reason for treatment failure in man and are the proper targets for the chemotherapist and immunotherapist. Since cure probably requires reduction of the total body burden of tumor cells to very small numbers (possibly to less than one cell), and since first-order kinetics of tumor cell kill by drugs appears to be a natural law in cancer chemotherapy, drug treatment should be started as soon as possible after likely noncurative primary treatment with surgery or radiation. Current knowledge of tumor cell population growth kinetics indicates that the growth fraction (viable tumor cells undergoing active cell replication) is inversely related to population size. Tumor cells in micrometastases should, therefore, be more sensitive to anticancer drugs active against anabolizing cells than are tumor cells in the larger, grossly apparent primary tumor from which they were derived. This indicates the probability that micrometastases will be effectively responsive to more drugs than is the primary and clinically apparent tumor from which they came. Studies with at least four metastatic and uniformly fatal murine solid tumors (lung, breast, colon, and melanoma) have demonstrated significantly improved cure rates with drug treatment following surgical removal of the grossly apparent primary tumor than can be obtained with either surgery or drug treatment when used alone. Further, both disease staging and drug dosage have been shown to influence cure rates of combined-modality treatment. With several mouse tumors, a significantly smaller number of viable tumor cells can establish lethal tumors in the presence of radiation-inactivated tumor cells than in their absence. This suggests that small numbers of residual viable tumor cells in radiation-treated tumor sites may be a greater threat to clinical cure than smaller tumor cell populations remaining in situ after surgery."} {"id": "PMID:178197", "title": "Optimal visualization of esophageal varices.", "content": "Twelve patients with known esophageal varices and willingness to cooperate were included in the study. Medications administered were placebo, 2 mg of glucagon, and 30 mg of propantheline bromide. All medications were given double-blind and crossover. On the basis of this study the authors believe that for optimal visualization of esophageal varices the following is the procedure of choice: (1) the patient should remain horizontal (this is best done in the left lateral position for comfort and ease of expectoration) for ten minutes after swallowing high density barium; (2) the patient should \"clear his throat\" frequently and expectorate all saliva (barium sticks to the pharynx and makes the patient want to swallow and \"clearing his throat\" by forced expiration helps the patient to expectorate this coating and prevents swallowing); (3) filming should be done in expiration in the supine (left posterior oblique to table top) position; and (4) in equivocal cases the examination can be repeated with an anticholinergic drug if the patient has no contraindications to its use. The patient should empty his bladder just before administration of the drug. The intelligent use of these factors should result in a saving of both fluoroscopic time and film, and give the radiologist a safe optimal diagnostic yield.", "contents": "Optimal visualization of esophageal varices. Twelve patients with known esophageal varices and willingness to cooperate were included in the study. Medications administered were placebo, 2 mg of glucagon, and 30 mg of propantheline bromide. All medications were given double-blind and crossover. On the basis of this study the authors believe that for optimal visualization of esophageal varices the following is the procedure of choice: (1) the patient should remain horizontal (this is best done in the left lateral position for comfort and ease of expectoration) for ten minutes after swallowing high density barium; (2) the patient should \"clear his throat\" frequently and expectorate all saliva (barium sticks to the pharynx and makes the patient want to swallow and \"clearing his throat\" by forced expiration helps the patient to expectorate this coating and prevents swallowing); (3) filming should be done in expiration in the supine (left posterior oblique to table top) position; and (4) in equivocal cases the examination can be repeated with an anticholinergic drug if the patient has no contraindications to its use. The patient should empty his bladder just before administration of the drug. The intelligent use of these factors should result in a saving of both fluoroscopic time and film, and give the radiologist a safe optimal diagnostic yield."} {"id": "PMID:178198", "title": "Involvement of the gastric antrum in M\u00e9n\u00e9trier's disease.", "content": "Thirteen cases of M\u00e9n\u00e9trier's disease from the files of the Armed Forces Institute of Pathology that could be documented pathologically and correlated with appropriate roentgenograms were analyzed for the distribution of folds. Enlarged folds occurred in a localized area or in several areas simultaniously. The greater curvature of the body was most often involved (77 percent), but the antrum was affected in almost one-half (46 percent) of the cases; thus, the concept of relative antral sparing is not valid, and the diagnosis should be considered when there is gastric rugal enlargement in any distribution. The condition seems to be classified best as a hyperplastic gastropathy rather than a hypertrophic gastritis.", "contents": "Involvement of the gastric antrum in M\u00e9n\u00e9trier's disease. Thirteen cases of M\u00e9n\u00e9trier's disease from the files of the Armed Forces Institute of Pathology that could be documented pathologically and correlated with appropriate roentgenograms were analyzed for the distribution of folds. Enlarged folds occurred in a localized area or in several areas simultaniously. The greater curvature of the body was most often involved (77 percent), but the antrum was affected in almost one-half (46 percent) of the cases; thus, the concept of relative antral sparing is not valid, and the diagnosis should be considered when there is gastric rugal enlargement in any distribution. The condition seems to be classified best as a hyperplastic gastropathy rather than a hypertrophic gastritis."} {"id": "PMID:178199", "title": "Normal pancreas and splenic variants simulating suprarenal and renal tumors.", "content": "Two cases of a normal pancreas simulating a renal or suprarenal mass on excretory urography are described. Three cases of unusually shaped spleens and one case of an accessory spleen mimicking renal and suprarenal masses on excretory urography are also presented. The rare entity of splenosis presenting as a renal \"mass\" on arteriography is also illustrated. The importance of selective arteriography in confirming or establishing the true nature of these pseudotumors which were initially seen on excretory urography is emphasized.", "contents": "Normal pancreas and splenic variants simulating suprarenal and renal tumors. Two cases of a normal pancreas simulating a renal or suprarenal mass on excretory urography are described. Three cases of unusually shaped spleens and one case of an accessory spleen mimicking renal and suprarenal masses on excretory urography are also presented. The rare entity of splenosis presenting as a renal \"mass\" on arteriography is also illustrated. The importance of selective arteriography in confirming or establishing the true nature of these pseudotumors which were initially seen on excretory urography is emphasized."} {"id": "PMID:178201", "title": "Rhabdomyosarcoma in the pediatric age group.", "content": "Forty-five consecutive cases of pediatric rhabdomyosarcoma were studied as to age at onset, histological type, primary site, stage of disease when first seen, method of treatment, and survival. It appears that rhabdomyosarcoma is a relatively radiosensitive tumor which can be controlled locally with radiation alone or in combination with surgery to excise the bulk of the tumor mass. On the other hand, chemotherapy must necessarily play a major role in treatment since most cases are first seen in the late stages of the disease. Close cooperation among a wide range of specialists, such as the pediatrician, radiation therapist, pediatric oncologist, pathologist, and surgeon is essential to accomplish a maximum therapeutic effect in the unfortunate children who develop this relatively rare but aggressive tumor.", "contents": "Rhabdomyosarcoma in the pediatric age group. Forty-five consecutive cases of pediatric rhabdomyosarcoma were studied as to age at onset, histological type, primary site, stage of disease when first seen, method of treatment, and survival. It appears that rhabdomyosarcoma is a relatively radiosensitive tumor which can be controlled locally with radiation alone or in combination with surgery to excise the bulk of the tumor mass. On the other hand, chemotherapy must necessarily play a major role in treatment since most cases are first seen in the late stages of the disease. Close cooperation among a wide range of specialists, such as the pediatrician, radiation therapist, pediatric oncologist, pathologist, and surgeon is essential to accomplish a maximum therapeutic effect in the unfortunate children who develop this relatively rare but aggressive tumor."} {"id": "PMID:178202", "title": "Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection.", "content": "Following total adrenalectomy in Cushing's syndrome associated with adrenal hyperplasia, but not with adrenal adenoma or malignancy, elements of the pituitary may be stimulated to grow rapidly and even aggressively. There is strong evidence to support the idea that there is a pre-existing tumor in many, if not all, of these cases. In some, the tumor may be too small to deform the sella turcica. After adrenalectomy, these patients should be observed carefully and frequently for hyperpigmentation, visual field defects, and sella turcica enlargement.", "contents": "Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection. Following total adrenalectomy in Cushing's syndrome associated with adrenal hyperplasia, but not with adrenal adenoma or malignancy, elements of the pituitary may be stimulated to grow rapidly and even aggressively. There is strong evidence to support the idea that there is a pre-existing tumor in many, if not all, of these cases. In some, the tumor may be too small to deform the sella turcica. After adrenalectomy, these patients should be observed carefully and frequently for hyperpigmentation, visual field defects, and sella turcica enlargement."} {"id": "PMID:178203", "title": "Changing clinical and roentgenographic patterns of necrotizing enterocolitis.", "content": "Necrotizing enterocolitis (NEC) occasionally deviates from the classical presentation of the disease. Small bowel dilatation and pneumatosis are frequently present prior to the actual onset of the clinical presentation. Pneumatosis intestinalis, an important diagnostic sign of NEC, is quite variable; it may be present, persist, worsen, or disappear; or at times it may not be present at all. A severe complication of necrotizing enterocolitis is perforation which in 50 percent of the cases presented without obvious free intra-abdominal air. Accumulation of fluid in the abdomen is stressed as strong evidence for perforation and a strong indication for surgery. The varying features indicate that NEC has a clinical spectrum that extends from benign to severe, and recognition of all these variations will lead to better diagnosis and to a better understanding of the disease. The clinical and roentgenologic variations make classification difficult but the variety most likely represents the combination of a great number of susceptible children and a greater recognition of the disease.", "contents": "Changing clinical and roentgenographic patterns of necrotizing enterocolitis. Necrotizing enterocolitis (NEC) occasionally deviates from the classical presentation of the disease. Small bowel dilatation and pneumatosis are frequently present prior to the actual onset of the clinical presentation. Pneumatosis intestinalis, an important diagnostic sign of NEC, is quite variable; it may be present, persist, worsen, or disappear; or at times it may not be present at all. A severe complication of necrotizing enterocolitis is perforation which in 50 percent of the cases presented without obvious free intra-abdominal air. Accumulation of fluid in the abdomen is stressed as strong evidence for perforation and a strong indication for surgery. The varying features indicate that NEC has a clinical spectrum that extends from benign to severe, and recognition of all these variations will lead to better diagnosis and to a better understanding of the disease. The clinical and roentgenologic variations make classification difficult but the variety most likely represents the combination of a great number of susceptible children and a greater recognition of the disease."} {"id": "PMID:178204", "title": "Arteriographic manifestations of pheochromocytoma.", "content": "Fourteen patients with 16 pheochromocytomas were studied arteriographically over a seven year period. Abnormalities identified the tumor site in 15 instances, but only a single subtle change was present in six of these. Renal artery stenosis was present in eight instances and was significant initially in at least one patient and may become significant in others. A hypertensive response to the study occurred in one-half the patients even though most had received adrenergic blocking drugs. Phentolamine remains the drug of choice in treatment.", "contents": "Arteriographic manifestations of pheochromocytoma. Fourteen patients with 16 pheochromocytomas were studied arteriographically over a seven year period. Abnormalities identified the tumor site in 15 instances, but only a single subtle change was present in six of these. Renal artery stenosis was present in eight instances and was significant initially in at least one patient and may become significant in others. A hypertensive response to the study occurred in one-half the patients even though most had received adrenergic blocking drugs. Phentolamine remains the drug of choice in treatment."} {"id": "PMID:178205", "title": "Embolic occlusion of the superior and inferior divisions of the middle cerebral artery with angiographic-clinical correlation.", "content": "Clinicians, in defining cerebral vascular syndromes, recognize embolism to the superior and inferior divisions of the middle cerebral artery in addition to embolism of the individual branches. In the present study 14 examples of arteriographically visualized divisional occlusion are analyzed, and a good correlation is demonstrated between the roentgenologic and clinical findings.", "contents": "Embolic occlusion of the superior and inferior divisions of the middle cerebral artery with angiographic-clinical correlation. Clinicians, in defining cerebral vascular syndromes, recognize embolism to the superior and inferior divisions of the middle cerebral artery in addition to embolism of the individual branches. In the present study 14 examples of arteriographically visualized divisional occlusion are analyzed, and a good correlation is demonstrated between the roentgenologic and clinical findings."} {"id": "PMID:178206", "title": "Cerebral blood volume alterations during fractional pneumoencephalography.", "content": "Simultaneous and continuous measurements of the cerebral blood volume (CBV), cerebrospinal fluid (CSF) and blood pressure were carried out in six patients during fractional pneumoencephalography in order to examine intracranial volumetric interactions. Three patients (Group A) showed normal encephalographic findings, and in three patients (Group B) communicating hydrocephalus with convexity block was found encephalographically. In all patients the injection of air was followed by an immediate increase of CSF pressure and blood pressure and a concomitant decrease of CBV. The initial CSF pressure was invariably re-established within 3 to 3.5 min. During this time interval the CBV of the patients of Group B decreased significantly and 30 percent more than that of Group A. Furthermore, after restoration of the original CSF pressure, CBV returned to its initial level in all patients of Group A, whereas it remained unchanged or showed a further decrease in the patients of Group B. Removal of an amount of CSF corresponding to half of the amount of injected air was followed by a significant reactive hyperemic response in two normal patients. The intracranial volumetric alterations during fractional pneumoencephalography are discussed in detail with respect to the underlying physiologic mechanisms and are suggested as a model for acute and low pressure hydrocephalus.", "contents": "Cerebral blood volume alterations during fractional pneumoencephalography. Simultaneous and continuous measurements of the cerebral blood volume (CBV), cerebrospinal fluid (CSF) and blood pressure were carried out in six patients during fractional pneumoencephalography in order to examine intracranial volumetric interactions. Three patients (Group A) showed normal encephalographic findings, and in three patients (Group B) communicating hydrocephalus with convexity block was found encephalographically. In all patients the injection of air was followed by an immediate increase of CSF pressure and blood pressure and a concomitant decrease of CBV. The initial CSF pressure was invariably re-established within 3 to 3.5 min. During this time interval the CBV of the patients of Group B decreased significantly and 30 percent more than that of Group A. Furthermore, after restoration of the original CSF pressure, CBV returned to its initial level in all patients of Group A, whereas it remained unchanged or showed a further decrease in the patients of Group B. Removal of an amount of CSF corresponding to half of the amount of injected air was followed by a significant reactive hyperemic response in two normal patients. The intracranial volumetric alterations during fractional pneumoencephalography are discussed in detail with respect to the underlying physiologic mechanisms and are suggested as a model for acute and low pressure hydrocephalus."} {"id": "PMID:178207", "title": "Frontal ventricular dimensions on normal computed tomography.", "content": "The computerized axial tomographic examinations of 200 normal patients and volunteers between the ages of ten to 81 years were evaluated. Determination of the ratio between the width of the brain and a dimension representing the distance between the outer borders of the lateral ventricles was made at two levels. This ratio, the cerebroventricular index, seems to be a reliable indicator of ventricular size. The standards vary with the age of the patient.", "contents": "Frontal ventricular dimensions on normal computed tomography. The computerized axial tomographic examinations of 200 normal patients and volunteers between the ages of ten to 81 years were evaluated. Determination of the ratio between the width of the brain and a dimension representing the distance between the outer borders of the lateral ventricles was made at two levels. This ratio, the cerebroventricular index, seems to be a reliable indicator of ventricular size. The standards vary with the age of the patient."} {"id": "PMID:178208", "title": "Bronchography in patients with hemoptysis.", "content": "Retrospective analysis of 196 cases suggests that bronchography has limited value in the evaluation of hemoptysis. Most patients with a single episode of hemoptysis and normal plain chest roentgenographic and bronchoscopic findings do not require bronchographic examination. Advances in cytologic and biopsy procedures (fiberoptic bronchoscopy, bronchial brushing, needle aspiration) have largely replaced the usefulness of bronchography even when the plain chest roentgenogram is abnormal.", "contents": "Bronchography in patients with hemoptysis. Retrospective analysis of 196 cases suggests that bronchography has limited value in the evaluation of hemoptysis. Most patients with a single episode of hemoptysis and normal plain chest roentgenographic and bronchoscopic findings do not require bronchographic examination. Advances in cytologic and biopsy procedures (fiberoptic bronchoscopy, bronchial brushing, needle aspiration) have largely replaced the usefulness of bronchography even when the plain chest roentgenogram is abnormal."} {"id": "PMID:178209", "title": "Isolated rotatory subluxation of the carpal navicular.", "content": "Rotatory subluxation of the carpal navicular can cause wrist pain and may lead to severe and disabling degenerative changes. Correct diagnosis depends on recognition of the typical roentgenographic signs. Sixteen patients with neither rheumatoid arthritis nor a lunate or a perilunate dislocation had rotatory subluxation in nineteen wrists. Many had only vague or remote histories of trauma. There were a navicular-lunate gap in all nineteen wrists, and foreshortening of the navicular in sixteen wrists, usually with a ring sign. The abnormalities were best demonstrated on well-centered posteroanterior roentgenograms of the wrist with the hand in slight radial deviation. In two patients, wrist arthrography demonstrated abnormal communication between radiocarpal and intercarpal joints.", "contents": "Isolated rotatory subluxation of the carpal navicular. Rotatory subluxation of the carpal navicular can cause wrist pain and may lead to severe and disabling degenerative changes. Correct diagnosis depends on recognition of the typical roentgenographic signs. Sixteen patients with neither rheumatoid arthritis nor a lunate or a perilunate dislocation had rotatory subluxation in nineteen wrists. Many had only vague or remote histories of trauma. There were a navicular-lunate gap in all nineteen wrists, and foreshortening of the navicular in sixteen wrists, usually with a ring sign. The abnormalities were best demonstrated on well-centered posteroanterior roentgenograms of the wrist with the hand in slight radial deviation. In two patients, wrist arthrography demonstrated abnormal communication between radiocarpal and intercarpal joints."} {"id": "PMID:178210", "title": "The notched articular process of C7 (dorsalization of C7).", "content": "The frequency of variation from the standard in the articular processes of C7 is very high (43.9 percent). These variations are: (1) A notch on the back of the superior articular facet. (2) Elongation the the \"articular pillary\" so that the posterior edge of the inferior articular process of C7 lies backward in relation to the posterior edges of the other cervical articular process. (3) A combination of both. Item 1 should not be mistaken for a fracture and item 2 should not be mistaken for a dislocation. These variants represent a partial dorsalization of C7.", "contents": "The notched articular process of C7 (dorsalization of C7). The frequency of variation from the standard in the articular processes of C7 is very high (43.9 percent). These variations are: (1) A notch on the back of the superior articular facet. (2) Elongation the the \"articular pillary\" so that the posterior edge of the inferior articular process of C7 lies backward in relation to the posterior edges of the other cervical articular process. (3) A combination of both. Item 1 should not be mistaken for a fracture and item 2 should not be mistaken for a dislocation. These variants represent a partial dorsalization of C7."} {"id": "PMID:178211", "title": "Spinal neurofibromatosis.", "content": "Neurofibromatosis is a congenital abnormality due to maldevelopment of the neurectoderm and mesoderm. Spinal abnormalities are a frequent occurrence and the roentgenological changes observed in 21 patients are presented. These include scoliosis, posterior scalloping of vertebral bodies, and the roentgenological features associated with intraspinal tumors and thoracic meningoceles.", "contents": "Spinal neurofibromatosis. Neurofibromatosis is a congenital abnormality due to maldevelopment of the neurectoderm and mesoderm. Spinal abnormalities are a frequent occurrence and the roentgenological changes observed in 21 patients are presented. These include scoliosis, posterior scalloping of vertebral bodies, and the roentgenological features associated with intraspinal tumors and thoracic meningoceles."} {"id": "PMID:178212", "title": "Demonstration and dimensional analysis of the normal pancreas with gray-scale echography.", "content": "For consistent identification of the normal pancreas, preliminary longitudinal scanning at, or near, the mid-line and subsequent oblique scanning in the long axis are necessary prerequisites in delineating the anatomic outline of the pancreas. The range of normal measurements for different anatomical regions of the pancreas was determined, based on the dimensional examinations of this organ in 328 patients free of pancreatic disease. These provide objective guidelines for analysis of the pancreas in abdominal echography. Echography provides a rapid, non-invasive method of imaging the pancreas. This study demonstrated that visualization of the pancreas as a separate structure does not imply that it is consequently abnormal.", "contents": "Demonstration and dimensional analysis of the normal pancreas with gray-scale echography. For consistent identification of the normal pancreas, preliminary longitudinal scanning at, or near, the mid-line and subsequent oblique scanning in the long axis are necessary prerequisites in delineating the anatomic outline of the pancreas. The range of normal measurements for different anatomical regions of the pancreas was determined, based on the dimensional examinations of this organ in 328 patients free of pancreatic disease. These provide objective guidelines for analysis of the pancreas in abdominal echography. Echography provides a rapid, non-invasive method of imaging the pancreas. This study demonstrated that visualization of the pancreas as a separate structure does not imply that it is consequently abnormal."} {"id": "PMID:178213", "title": "Intra- and extracerebral arachnoid cyst. An atypical roentgenographic presentation.", "content": "Arachnoid cysts present in a variety of ways, and the preoperative diagnosis usually requires a high degree of suspicion. Bony changes consistent with a chronic focal mass effect, a relative paucity of clinical findings compared to the size of the lesion, and an extracerebral mass with an intracerebral component suggest the possibility. We present a case in which there appears to be a large, deep intracerebral mass associated with an extracerebral expansion.", "contents": "Intra- and extracerebral arachnoid cyst. An atypical roentgenographic presentation. Arachnoid cysts present in a variety of ways, and the preoperative diagnosis usually requires a high degree of suspicion. Bony changes consistent with a chronic focal mass effect, a relative paucity of clinical findings compared to the size of the lesion, and an extracerebral mass with an intracerebral component suggest the possibility. We present a case in which there appears to be a large, deep intracerebral mass associated with an extracerebral expansion."} {"id": "PMID:178214", "title": "Radiation-induced renovascular hypertension.", "content": "Radiation is known to produce changes in the small vessels and interstitium of the kidneys resulting in hypertension. Two cases of renal artery stenosis and resultant hypertension secondary to abdominal irradiation are reported and the literature is reviewed.", "contents": "Radiation-induced renovascular hypertension. Radiation is known to produce changes in the small vessels and interstitium of the kidneys resulting in hypertension. Two cases of renal artery stenosis and resultant hypertension secondary to abdominal irradiation are reported and the literature is reviewed."} {"id": "PMID:178215", "title": "Postesophageal narrowing associated with Barrett esophagus.", "content": "Two children have been found to have partially obstructing lesions beyond the esophagus in association with mid-esophageal stricture. Both were found to have columnar epithelium-lined (Barrett) esophagus, and gastro-esophageal reflux. The more distal obstruction, in the pylorus and descending duodenum respectively, may have contributed to the development of the Barrett esophagus. It is recommended that any barium study of the esophagus which reveals an unexplained stricture should include visualization through the duodenojejunal junction as an aid to diagnosis, management, and understanding.", "contents": "Postesophageal narrowing associated with Barrett esophagus. Two children have been found to have partially obstructing lesions beyond the esophagus in association with mid-esophageal stricture. Both were found to have columnar epithelium-lined (Barrett) esophagus, and gastro-esophageal reflux. The more distal obstruction, in the pylorus and descending duodenum respectively, may have contributed to the development of the Barrett esophagus. It is recommended that any barium study of the esophagus which reveals an unexplained stricture should include visualization through the duodenojejunal junction as an aid to diagnosis, management, and understanding."} {"id": "PMID:178216", "title": "Multichambered bladder anomalies.", "content": "This report reviews multichambered bladder conditions, offers a workable classification of them, presents a detailed case report, and discusses the possible causes of these anomalies. We wish to stress the importance of careful examination of the genital area in the newborn and early roentgenologic evaluation of the genito-urinary system when an anomaly is found.", "contents": "Multichambered bladder anomalies. This report reviews multichambered bladder conditions, offers a workable classification of them, presents a detailed case report, and discusses the possible causes of these anomalies. We wish to stress the importance of careful examination of the genital area in the newborn and early roentgenologic evaluation of the genito-urinary system when an anomaly is found."} {"id": "PMID:178217", "title": "Localized nodular synovitis of the knee: a report of two cases with abnormal arthrograms.", "content": "The arthrographic appearance in two cases of localized PVS of the knee involving the region of the infrapatellar fat pad is reported. Lesions in this area may present with confusing symptomatology, and the true abnormality may be overlooked in a search for meniscal lesion. The arthrographic picture is non-specific and a number of entities must be considered.", "contents": "Localized nodular synovitis of the knee: a report of two cases with abnormal arthrograms. The arthrographic appearance in two cases of localized PVS of the knee involving the region of the infrapatellar fat pad is reported. Lesions in this area may present with confusing symptomatology, and the true abnormality may be overlooked in a search for meniscal lesion. The arthrographic picture is non-specific and a number of entities must be considered."} {"id": "PMID:178219", "title": "Transfemoral lumbar epidural venography.", "content": "Lumbar epidural venography performed in 107 patients with normal or nondiagnostic myelograms resulted in correct preoperative diagnosis in 25 of 27 patients (92%) with herniated disc disease and three of six patients (50%) with nerve root compression without associated disc herniation. Compression or occlusion of an epidural and/or radicular vein at the disc level is the most significant venographic abnormality. Potentially confusing venographic findings such as flow defects, extravertebral veins mimicking epidural veins, and occlusion of radicular veins by the catheter must be recognized to prevent false diagnoses. Lumbar epidural venography is valuable for the diagnoses of herniated lumbar discs not demonstrated by myelography.", "contents": "Transfemoral lumbar epidural venography. Lumbar epidural venography performed in 107 patients with normal or nondiagnostic myelograms resulted in correct preoperative diagnosis in 25 of 27 patients (92%) with herniated disc disease and three of six patients (50%) with nerve root compression without associated disc herniation. Compression or occlusion of an epidural and/or radicular vein at the disc level is the most significant venographic abnormality. Potentially confusing venographic findings such as flow defects, extravertebral veins mimicking epidural veins, and occlusion of radicular veins by the catheter must be recognized to prevent false diagnoses. Lumbar epidural venography is valuable for the diagnoses of herniated lumbar discs not demonstrated by myelography."} {"id": "PMID:178220", "title": "Epidural venography: diagnosis of herniated lumbar intervertebral disc and other disease of the epidural space.", "content": "Epidural venography is a simple and safe procedure for the diagnosis of herniated intervertebral disc and other disease of the epidural space. It is especially useful in symptomatic patients with normal or equivocal myelographic findings. The accuracy rate of positive venograms is 88.2% in this series of 58 patients. Five illustrative cases are presented.", "contents": "Epidural venography: diagnosis of herniated lumbar intervertebral disc and other disease of the epidural space. Epidural venography is a simple and safe procedure for the diagnosis of herniated intervertebral disc and other disease of the epidural space. It is especially useful in symptomatic patients with normal or equivocal myelographic findings. The accuracy rate of positive venograms is 88.2% in this series of 58 patients. Five illustrative cases are presented."} {"id": "PMID:178221", "title": "The cardiac pacemaker: a different twist.", "content": "A new complication of transvenous pacing is described. Twists developing in an endocardial lead indicate that the pulse generator pocket is too large. Pacemaker failure because of electrode dislodgement or lead fracture will ensue.", "contents": "The cardiac pacemaker: a different twist. A new complication of transvenous pacing is described. Twists developing in an endocardial lead indicate that the pulse generator pocket is too large. Pacemaker failure because of electrode dislodgement or lead fracture will ensue."} {"id": "PMID:178222", "title": "Iliocaval thrombi in pulmonary thromboembolic disease.", "content": "Rational management of patients with pulmonary thromboembolic disease should include assessment of the risk of additional emboli. Other authors have shown that the possibility of fatal pulmonary embolism is higher when the iliofemoral system contains thrombus, and it is recommended that vena caval interruption rather than simple anticoagulation is indicated. Additional factors governing the therapeutic choice should include the magnitude of the original embolic occlusion as well as the presence of antecedent cardiopulmonary disease. In these instances large thrombi in the iliocaval system should be regarded as potentially life threatening. A sequence of angiography beginning with right iliac and vena caval opacification, proceeding to pulmonary arteriography, and terminating with retrograde left iliac vein study provided information needed to individualize the therapeutic approach. Several case reports illustrate the spectrum of abnormalities and their therapeutic implications.", "contents": "Iliocaval thrombi in pulmonary thromboembolic disease. Rational management of patients with pulmonary thromboembolic disease should include assessment of the risk of additional emboli. Other authors have shown that the possibility of fatal pulmonary embolism is higher when the iliofemoral system contains thrombus, and it is recommended that vena caval interruption rather than simple anticoagulation is indicated. Additional factors governing the therapeutic choice should include the magnitude of the original embolic occlusion as well as the presence of antecedent cardiopulmonary disease. In these instances large thrombi in the iliocaval system should be regarded as potentially life threatening. A sequence of angiography beginning with right iliac and vena caval opacification, proceeding to pulmonary arteriography, and terminating with retrograde left iliac vein study provided information needed to individualize the therapeutic approach. Several case reports illustrate the spectrum of abnormalities and their therapeutic implications."} {"id": "PMID:178223", "title": "Venography in penetrating injuries of the extremities.", "content": "Of 30 consecutive cases of penetrating injuries to the extremities studied both by arteriography and venography, five were found to have significant venous injuries. Three of these cases are presented to show the value of venography in detecting inadequate venous collateral circulation, intraluminal thrombus, and venous obstruction. It is suggested that preoperative venography will compliment arteriography, aid in the diagnosis of venous injuries, demonstrate variable venous anatomy, and outline other venous pathology outside of the area of trauma.", "contents": "Venography in penetrating injuries of the extremities. Of 30 consecutive cases of penetrating injuries to the extremities studied both by arteriography and venography, five were found to have significant venous injuries. Three of these cases are presented to show the value of venography in detecting inadequate venous collateral circulation, intraluminal thrombus, and venous obstruction. It is suggested that preoperative venography will compliment arteriography, aid in the diagnosis of venous injuries, demonstrate variable venous anatomy, and outline other venous pathology outside of the area of trauma."} {"id": "PMID:178224", "title": "Selective arterial embolization for control of hemorrhage in pelvic malignancy: femoral and brachial catheter approaches.", "content": "Selective transcatheter embolization with Gelfoam pledgets was used to control intractable pelvic hemorrhage in two patients with gynecologic malignancy. There were no complications or sequelae associated with the procedure, and no further bleeding occurred. This method requires only Seldinger catheterization techniques under local anesthesia and should be considered in patients whose medical condition precludes major surgery or in whom operative ligation cannot be performed.", "contents": "Selective arterial embolization for control of hemorrhage in pelvic malignancy: femoral and brachial catheter approaches. Selective transcatheter embolization with Gelfoam pledgets was used to control intractable pelvic hemorrhage in two patients with gynecologic malignancy. There were no complications or sequelae associated with the procedure, and no further bleeding occurred. This method requires only Seldinger catheterization techniques under local anesthesia and should be considered in patients whose medical condition precludes major surgery or in whom operative ligation cannot be performed."} {"id": "PMID:178225", "title": "Peripheral embolization complicating bilateral renal infarction with gelfoam.", "content": "Selective arterial embolization is a technique with wide therapeutic applicability. However, regardless of the nature of the embolic particles, reflux into the aorta with peripheral embolization is a serious potential complication. A case is described in which this complication occurred. We recommend that all such embolizations be performed with a balloon catheter occluding the target artery.", "contents": "Peripheral embolization complicating bilateral renal infarction with gelfoam. Selective arterial embolization is a technique with wide therapeutic applicability. However, regardless of the nature of the embolic particles, reflux into the aorta with peripheral embolization is a serious potential complication. A case is described in which this complication occurred. We recommend that all such embolizations be performed with a balloon catheter occluding the target artery."} {"id": "PMID:178226", "title": "Crossed renal ectopia: angiographic findings in six cases.", "content": "Angiographic findings in six patients with crossed renal ectopia are reported. Crossed fused ectopia was present in four cases, and the remaining two had single crossed ectopic kidneys. All kidneys, including the nonectopic ones, had an anomalous blood supply. No constant arterial pattern was discernible, and renal arteries were found to arise from the aorta both above and below the normal level as well as from the iliac arteries. It is suggested that angiography be undertaken in all cases when surgery is contemplated.", "contents": "Crossed renal ectopia: angiographic findings in six cases. Angiographic findings in six patients with crossed renal ectopia are reported. Crossed fused ectopia was present in four cases, and the remaining two had single crossed ectopic kidneys. All kidneys, including the nonectopic ones, had an anomalous blood supply. No constant arterial pattern was discernible, and renal arteries were found to arise from the aorta both above and below the normal level as well as from the iliac arteries. It is suggested that angiography be undertaken in all cases when surgery is contemplated."} {"id": "PMID:178227", "title": "Angiographically induced renal failure and its radiographic detection.", "content": "Decreased renal function following arteriography is much more common than is currently realized. Steps to detect this failure are necessary, especially in high risk patients, so that stressful situations such as surgery can be avoided. A recently performed prospective random study of 100 patients undergoing angiography demonstrated a 10% incidence of renal failure. Those patients most at risk had preexisting renal disease as indicated by an elevated serum creatinine and/or cardiovascular disease severe enough to require digoxin, diuretics, or nitroglycerin. No cases of renal failure occurred in the absence of one or both of these processes. The likelihood of postangiographic renal failure was unrelated to the quantity of contrast as measured either by total volume or per kilogram body weight.", "contents": "Angiographically induced renal failure and its radiographic detection. Decreased renal function following arteriography is much more common than is currently realized. Steps to detect this failure are necessary, especially in high risk patients, so that stressful situations such as surgery can be avoided. A recently performed prospective random study of 100 patients undergoing angiography demonstrated a 10% incidence of renal failure. Those patients most at risk had preexisting renal disease as indicated by an elevated serum creatinine and/or cardiovascular disease severe enough to require digoxin, diuretics, or nitroglycerin. No cases of renal failure occurred in the absence of one or both of these processes. The likelihood of postangiographic renal failure was unrelated to the quantity of contrast as measured either by total volume or per kilogram body weight."} {"id": "PMID:178228", "title": "Arthrographic evaluation of injuries of the first metacarpophalangeal joint: gamekeeper's thumb.", "content": "The radiographic evaluation of gamekeeper's thumb is described in an experimental study in nine cadaveric hands. After the application of radial stress at the metacarpophalangeal joint in the extended and abducted thumbs in an attempt to create defects in the ulnar collateral ligament, initial and stress radiography and arthrography were employed. In four cadavers a fracture of the proximal phalanx was noted; stress radiography revealed variability in joint stability. Arthrography outlined ulnar extravasation in six of the nine cadavers; surgical confirmation of a capsular tear was obtained following careful dissection in each of these six cadavers. It would appear that plain films, stress radiography, and arthrography complement each other in the diagnosis of gamekeeper's thumb.", "contents": "Arthrographic evaluation of injuries of the first metacarpophalangeal joint: gamekeeper's thumb. The radiographic evaluation of gamekeeper's thumb is described in an experimental study in nine cadaveric hands. After the application of radial stress at the metacarpophalangeal joint in the extended and abducted thumbs in an attempt to create defects in the ulnar collateral ligament, initial and stress radiography and arthrography were employed. In four cadavers a fracture of the proximal phalanx was noted; stress radiography revealed variability in joint stability. Arthrography outlined ulnar extravasation in six of the nine cadavers; surgical confirmation of a capsular tear was obtained following careful dissection in each of these six cadavers. It would appear that plain films, stress radiography, and arthrography complement each other in the diagnosis of gamekeeper's thumb."} {"id": "PMID:178229", "title": "Isolated fracture of the medial portion of the lateral mass of the atlas: a previously undescribed entity.", "content": "Four cases of fracture of the medial aspect of the lateral mass of the atlas are presented. Unlike most cases of atlantal fracture, definite history of a blow to the vertex could not be established. While the exact mechanism of injury is unknown, it is postulated that the bone fragment is produced by a combination of stretching the ligamentum transversarium and pressure on the lateral mass due to contraction of the neck muscles. All four patients were neurologically intact and complained of pain in the distribution of the greater occipital nerve. It is suggested that this fracture might be identified more often in patients with similar histories and complaints by use of laminagraphy, since part or all of the atlas is frequently obscured on routine open mouth roentgenograms of the upper cervical spine.", "contents": "Isolated fracture of the medial portion of the lateral mass of the atlas: a previously undescribed entity. Four cases of fracture of the medial aspect of the lateral mass of the atlas are presented. Unlike most cases of atlantal fracture, definite history of a blow to the vertex could not be established. While the exact mechanism of injury is unknown, it is postulated that the bone fragment is produced by a combination of stretching the ligamentum transversarium and pressure on the lateral mass due to contraction of the neck muscles. All four patients were neurologically intact and complained of pain in the distribution of the greater occipital nerve. It is suggested that this fracture might be identified more often in patients with similar histories and complaints by use of laminagraphy, since part or all of the atlas is frequently obscured on routine open mouth roentgenograms of the upper cervical spine."} {"id": "PMID:178230", "title": "Concomitant dislocation and intraarticular foreign body: a rare complication of the Charnley total hip arthroplasty.", "content": "In the Charnley total hip arthroplasty, periarticular foreign bodies represent potential foci for intraarticular migration at the time of hip dislocation. This complication, although very rare, should be verified radiographically to prevent unsucessful attempts at closed reduction. Although intraarticular radiopaque foreign bodies should be identified on plain radiographs of the hip, intraarticular radiolucent foreign bodies require positive-contrast arthrography for identification. Two illustrative cases are presented.", "contents": "Concomitant dislocation and intraarticular foreign body: a rare complication of the Charnley total hip arthroplasty. In the Charnley total hip arthroplasty, periarticular foreign bodies represent potential foci for intraarticular migration at the time of hip dislocation. This complication, although very rare, should be verified radiographically to prevent unsucessful attempts at closed reduction. Although intraarticular radiopaque foreign bodies should be identified on plain radiographs of the hip, intraarticular radiolucent foreign bodies require positive-contrast arthrography for identification. Two illustrative cases are presented."} {"id": "PMID:178231", "title": "Embryogenesis of the human occipital bone.", "content": "From an original study of fetal specimens, the embryogenesis of the human occipital bone is described. The occipital bone in man is derived from cartilage, except for the interparietal segment which has a membranous origin. Normally there is no midline cerebellar fissure or synchondrosis.", "contents": "Embryogenesis of the human occipital bone. From an original study of fetal specimens, the embryogenesis of the human occipital bone is described. The occipital bone in man is derived from cartilage, except for the interparietal segment which has a membranous origin. Normally there is no midline cerebellar fissure or synchondrosis."} {"id": "PMID:178232", "title": "99MTc-diphosphonate uptake in neuroblastoma.", "content": "Marked uptake of 99mTc-diphosphonate was noted in an extraadrenal neuroblastoma. Calcification was not demonstrable on radiographic or light microscopic examination, nor was crystalline material identified on electron microscopic examination; capillaries in the lesion appeared to be intact. Similar uptake of phosphate radiopharmaceuticals by a variety of lesions has been reported, and possible mechanisms for this phenomenon are discussed.", "contents": "99MTc-diphosphonate uptake in neuroblastoma. Marked uptake of 99mTc-diphosphonate was noted in an extraadrenal neuroblastoma. Calcification was not demonstrable on radiographic or light microscopic examination, nor was crystalline material identified on electron microscopic examination; capillaries in the lesion appeared to be intact. Similar uptake of phosphate radiopharmaceuticals by a variety of lesions has been reported, and possible mechanisms for this phenomenon are discussed."} {"id": "PMID:178233", "title": "Adjuvant chemoimmunotherapy in advanced lesions of the head and neck.", "content": "Growth of malignant tumors of the head and neck has been associated with progressive impairment of immunologic activity. Successful control of disease has been shown to reverse this defect. Preliminary results of a nonrandomized trial reduced recurrence of head and neck cancer for a median time of 11.5 months in eight of 10 patients who received chemoimmunotherapy adjuvant to surgical resection or radiation treatment. The number of patients in the series was small and the followup time too short to determine the length of effectiveness for this treatment. Based on these results, a new protocol has been initiated to randomize patients with advanced T3 and T4 lesions into groups for comparison of adjuvant chemotherapy alone with adjuvant chemoimmunotherapy.", "contents": "Adjuvant chemoimmunotherapy in advanced lesions of the head and neck. Growth of malignant tumors of the head and neck has been associated with progressive impairment of immunologic activity. Successful control of disease has been shown to reverse this defect. Preliminary results of a nonrandomized trial reduced recurrence of head and neck cancer for a median time of 11.5 months in eight of 10 patients who received chemoimmunotherapy adjuvant to surgical resection or radiation treatment. The number of patients in the series was small and the followup time too short to determine the length of effectiveness for this treatment. Based on these results, a new protocol has been initiated to randomize patients with advanced T3 and T4 lesions into groups for comparison of adjuvant chemotherapy alone with adjuvant chemoimmunotherapy."} {"id": "PMID:178234", "title": "Immunotherapy of malignancies: current status.", "content": "The results of various in vitro analyses indicate there is an active immune response against antigens associated with human malignancies. This immune response apparently can be augmented by nonspecific immunologic stimulates such as BCG. These agents are effective for destroying tumor when injected locally into intracutaneous disease but are not as effective for subcutaneous disease. Preliminary clinical trials indicated that immune stimulants are effective when administered systemically. The effect is only minimal for diseminated disease, but the therapeutic benefit is clearly augmented for patients with a minimal residual tumor burden, such as those patients with metastases to regional lymph nodes. Thus immunotherapy is a systemically active mode of therapy. Its toxicity is minimal, and it appears to be effective in a wide spectrum of the disease. However, immunotherapy is not effective for a large residual tumor burden; consequently it must be used in combination with other modes of treatment such as irradiation therapy or chemotherapy. Early experiences with BCG immunotherapy for malignant melanoma and C. parvum for oat cell carcinoma are encouraging. It is remarkable that a nonspecific immunologic stimulant does, in fact, have this effect. Immunotherapy experiments in animals suggest that in order to achieve maximal benefit. BCG must have close contact with tumor cells or must be combined with a tumor-associated antigen. If these principles are true for man, it would seem that improvements for nonspecific immunotherapy in human neoplasms would be further augmented if a tumor-related antigen could be extracted from human tumours and combined with a nonspecific immunologic stimulant.", "contents": "Immunotherapy of malignancies: current status. The results of various in vitro analyses indicate there is an active immune response against antigens associated with human malignancies. This immune response apparently can be augmented by nonspecific immunologic stimulates such as BCG. These agents are effective for destroying tumor when injected locally into intracutaneous disease but are not as effective for subcutaneous disease. Preliminary clinical trials indicated that immune stimulants are effective when administered systemically. The effect is only minimal for diseminated disease, but the therapeutic benefit is clearly augmented for patients with a minimal residual tumor burden, such as those patients with metastases to regional lymph nodes. Thus immunotherapy is a systemically active mode of therapy. Its toxicity is minimal, and it appears to be effective in a wide spectrum of the disease. However, immunotherapy is not effective for a large residual tumor burden; consequently it must be used in combination with other modes of treatment such as irradiation therapy or chemotherapy. Early experiences with BCG immunotherapy for malignant melanoma and C. parvum for oat cell carcinoma are encouraging. It is remarkable that a nonspecific immunologic stimulant does, in fact, have this effect. Immunotherapy experiments in animals suggest that in order to achieve maximal benefit. BCG must have close contact with tumor cells or must be combined with a tumor-associated antigen. If these principles are true for man, it would seem that improvements for nonspecific immunotherapy in human neoplasms would be further augmented if a tumor-related antigen could be extracted from human tumours and combined with a nonspecific immunologic stimulant."} {"id": "PMID:178237", "title": "Angiography in Crohn's disease revisited.", "content": "The diagnostic value of angiography was studied in 116 patients with Crohn's disease. Angiograms showed abnormalities in over 90% of the cases. Many angiographic features were nonspecific; only the \"zoning sign\" and the presence of paraintestinal mesenteric neovasculature were considered diagnostic. Crohn's colitis could be distinguished from ulcerative colitis in only 30% of the cases. Angiography, as a diagnostic adjunct to barium studies, will reveal the presence of lesions and their extent. This is particularly important in suspected postoperative recurrence of Crohn's disease. Angiography is a potential differential diagnostic aid in doubtful cases of inflammatory and malignant bowel disease.", "contents": "Angiography in Crohn's disease revisited. The diagnostic value of angiography was studied in 116 patients with Crohn's disease. Angiograms showed abnormalities in over 90% of the cases. Many angiographic features were nonspecific; only the \"zoning sign\" and the presence of paraintestinal mesenteric neovasculature were considered diagnostic. Crohn's colitis could be distinguished from ulcerative colitis in only 30% of the cases. Angiography, as a diagnostic adjunct to barium studies, will reveal the presence of lesions and their extent. This is particularly important in suspected postoperative recurrence of Crohn's disease. Angiography is a potential differential diagnostic aid in doubtful cases of inflammatory and malignant bowel disease."} {"id": "PMID:178238", "title": "Hepatic angiography in ulcerative colitis and Crohn's disease.", "content": "Liver angiography was performed in 13 patients with Crohn's disease and three with ulcerative colitis. Of these patients, 13 underwent liver biopsy, and findings were correlated with results of angiography and biochemical tests. Twelve liver biopsies were abnormal, primarily showing fatty infiltration and reactive hepatitis. Thirteen angiographies were abnormal, with widened and tortuous liver arteries being the most common finding. Liver function tests were within normal limits for all but three of the 16 patients, thus correlating poorly with findings of the other tests. These data show that angiography is useful in detecting hepatic abnormality, but evaluation with liver biopsy is necessary to determine the nature of the lesion.", "contents": "Hepatic angiography in ulcerative colitis and Crohn's disease. Liver angiography was performed in 13 patients with Crohn's disease and three with ulcerative colitis. Of these patients, 13 underwent liver biopsy, and findings were correlated with results of angiography and biochemical tests. Twelve liver biopsies were abnormal, primarily showing fatty infiltration and reactive hepatitis. Thirteen angiographies were abnormal, with widened and tortuous liver arteries being the most common finding. Liver function tests were within normal limits for all but three of the 16 patients, thus correlating poorly with findings of the other tests. These data show that angiography is useful in detecting hepatic abnormality, but evaluation with liver biopsy is necessary to determine the nature of the lesion."} {"id": "PMID:178239", "title": "Megacystis-microcolon-intestinal hypoperistalsis syndrome: a new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls.", "content": "Five newborn girls presented with small intestinal obstruction and microcolon and a giant bladder (megacystis). Organic causes of obstruction were not found, and the gastrointestinal tract failed to function after appropriate diversion. Two died in the postoperative period, two lived several months on central venous hyperalimentation, and one died at 34 months of age following chronic though intermittent hyperalimentation. Pathologic studies showed an abundance of ganglion cells in both dilated and narrowed areas of intestine; the combined small bowel-colon length was one-third of normal in the absence of an evident obstructive or vascular insult. The five patients represent the most severe manifestation of defective intestinal peristalsis in a larger group of distended newborns in whom organic gastrointestinal obstruction is not found. Treatment with central venous hyperalimentation may sustain life, and some patients eventually recover gastrointestinal function. The hypoperistalsis is largely refractory to pharmacologic treatment; its cause is unknown.", "contents": "Megacystis-microcolon-intestinal hypoperistalsis syndrome: a new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls. Five newborn girls presented with small intestinal obstruction and microcolon and a giant bladder (megacystis). Organic causes of obstruction were not found, and the gastrointestinal tract failed to function after appropriate diversion. Two died in the postoperative period, two lived several months on central venous hyperalimentation, and one died at 34 months of age following chronic though intermittent hyperalimentation. Pathologic studies showed an abundance of ganglion cells in both dilated and narrowed areas of intestine; the combined small bowel-colon length was one-third of normal in the absence of an evident obstructive or vascular insult. The five patients represent the most severe manifestation of defective intestinal peristalsis in a larger group of distended newborns in whom organic gastrointestinal obstruction is not found. Treatment with central venous hyperalimentation may sustain life, and some patients eventually recover gastrointestinal function. The hypoperistalsis is largely refractory to pharmacologic treatment; its cause is unknown."} {"id": "PMID:178240", "title": "Multiple \"bull's-eye\" lesions in gastric lymphoma.", "content": "Three adolescent patients with multiple gastric target lesions and gastric lymphoma are reported. Each had either histiocytic or poorly differentiated lymphoma. The literature was reviewed to ascertain whether multiple gastric lymphomatous target lesions were confined to adolescent patients or to patients with a particular histologic subtype. Review of 119 cases in the literature did not support either hypothesis.", "contents": "Multiple \"bull's-eye\" lesions in gastric lymphoma. Three adolescent patients with multiple gastric target lesions and gastric lymphoma are reported. Each had either histiocytic or poorly differentiated lymphoma. The literature was reviewed to ascertain whether multiple gastric lymphomatous target lesions were confined to adolescent patients or to patients with a particular histologic subtype. Review of 119 cases in the literature did not support either hypothesis."} {"id": "PMID:178241", "title": "Vascular impressions of the gut secondary to chronic vascular occlusive disease.", "content": "Clinical diagnosis of chronic vascular occlusive disease is difficult since symptoms are often vague. The presence of discrete extrinsic contoural defects along the medial aspect of the descending duodenum or proximal small bowel is a useful diagnostic feature in such patients. Five of eight patients with chronic vascular occlusion who had examination of the upper gastrointestinal tract demonstrated this finding. If presented with this radiographic observation on barium study, visceral arteriography should then be considered.", "contents": "Vascular impressions of the gut secondary to chronic vascular occlusive disease. Clinical diagnosis of chronic vascular occlusive disease is difficult since symptoms are often vague. The presence of discrete extrinsic contoural defects along the medial aspect of the descending duodenum or proximal small bowel is a useful diagnostic feature in such patients. Five of eight patients with chronic vascular occlusion who had examination of the upper gastrointestinal tract demonstrated this finding. If presented with this radiographic observation on barium study, visceral arteriography should then be considered."} {"id": "PMID:178242", "title": "A new concept of ascitic fluid distribution.", "content": "Of 26 patients with ascites examined by B-mode ultrasonography, 14 had scans appropriate for evaluating the presence of fluid within the abdominal cavity. These studies demonstrate localization of fluid anteriorly around the tip of the liver and emphasize the importance of such factors as density relationships and the \"pliability\" of the anterior abdominal wall in the distribution of ascitic fluid. A reveiw of the literature is presented.", "contents": "A new concept of ascitic fluid distribution. Of 26 patients with ascites examined by B-mode ultrasonography, 14 had scans appropriate for evaluating the presence of fluid within the abdominal cavity. These studies demonstrate localization of fluid anteriorly around the tip of the liver and emphasize the importance of such factors as density relationships and the \"pliability\" of the anterior abdominal wall in the distribution of ascitic fluid. A reveiw of the literature is presented."} {"id": "PMID:178243", "title": "Glucagon and barium enema examinations: a controlled clinical trial.", "content": "In a double-blind crossover clinical trial, 10 healthy volunteers received placebo and 2 mg glucagon intramuscularly preceding barium enema examination on separate days. In addition, 50 patients were given either placebo or 2 mg glucagon prior to barium enema examination in a double-blind study. The results of 38 variables determined on each study population were similar. When glucagon was given, both the patients and examiners noted significantly less discomfort and more bowel relaxation. There were no significant changes in pulse, blood pressure, or electrocardiogram. Adverse reactions did not occur frequently enough to allow confident comparison of placebo and glucagon. It is concluded that the use of glucagon can provide a more comfortable barium examination with acceptable safety.", "contents": "Glucagon and barium enema examinations: a controlled clinical trial. In a double-blind crossover clinical trial, 10 healthy volunteers received placebo and 2 mg glucagon intramuscularly preceding barium enema examination on separate days. In addition, 50 patients were given either placebo or 2 mg glucagon prior to barium enema examination in a double-blind study. The results of 38 variables determined on each study population were similar. When glucagon was given, both the patients and examiners noted significantly less discomfort and more bowel relaxation. There were no significant changes in pulse, blood pressure, or electrocardiogram. Adverse reactions did not occur frequently enough to allow confident comparison of placebo and glucagon. It is concluded that the use of glucagon can provide a more comfortable barium examination with acceptable safety."} {"id": "PMID:178244", "title": "Spontaneous internal drainage of pancreatic pseudocysts.", "content": "Six cases are reported in which spontaneous internal drainage between a pancreatic pseudocyst and the alimentary tract became established. In each instance the communication was demonstrated radiologically. The clinical circumstances and radiographic features of these cases are described, and the existing literature pertaining to this phenomenon is reviewed.", "contents": "Spontaneous internal drainage of pancreatic pseudocysts. Six cases are reported in which spontaneous internal drainage between a pancreatic pseudocyst and the alimentary tract became established. In each instance the communication was demonstrated radiologically. The clinical circumstances and radiographic features of these cases are described, and the existing literature pertaining to this phenomenon is reviewed."} {"id": "PMID:178245", "title": "Lumbar epidural venography in the diagnosis of disc herniations.", "content": "Epidural venography is a relatively simple and highly accurate method of diagnosing disc herniations in the lumbar region. Good opacification of the epidural venous plexus can be obtained by selective catheterization of ascending lumbar and/or internal iliac veins. Experience with 227 cases is described. The examination appears to be at least as accurate as myelography at the L4-L5 level and more reliable than myelography in cases of lateral disc herniations at L5-SI. Epidural venography is recommended as the examination of choice in patients with suspected lumbar disc herniation.", "contents": "Lumbar epidural venography in the diagnosis of disc herniations. Epidural venography is a relatively simple and highly accurate method of diagnosing disc herniations in the lumbar region. Good opacification of the epidural venous plexus can be obtained by selective catheterization of ascending lumbar and/or internal iliac veins. Experience with 227 cases is described. The examination appears to be at least as accurate as myelography at the L4-L5 level and more reliable than myelography in cases of lateral disc herniations at L5-SI. Epidural venography is recommended as the examination of choice in patients with suspected lumbar disc herniation."} {"id": "PMID:178246", "title": "Experimental induction of hypoparathyroidism with parathyroid hormone antibodies.", "content": "This study describes the effect of a single injection of parathyroid hormone antiserum on the serum calcium, serum phosphate, urinary cyclic AMP, and urinary phosphate levels in the intact perfused rat. A significant decline in serum calcium level with concomitant elevation in serum phosphate level and decreased urinary excretion of phosphate and cyclic AMP was noted. These findings strongly suggest that a transient hypoparathyroid state was induced by the parathyroid hormone antiserum.", "contents": "Experimental induction of hypoparathyroidism with parathyroid hormone antibodies. This study describes the effect of a single injection of parathyroid hormone antiserum on the serum calcium, serum phosphate, urinary cyclic AMP, and urinary phosphate levels in the intact perfused rat. A significant decline in serum calcium level with concomitant elevation in serum phosphate level and decreased urinary excretion of phosphate and cyclic AMP was noted. These findings strongly suggest that a transient hypoparathyroid state was induced by the parathyroid hormone antiserum."} {"id": "PMID:178247", "title": "[Inhibition by diethyldithiocarbamate (DEDTC) of acute hepatotoxic effects induced by polyhalogenated hydrocarbons (PHHC)].", "content": "Hemoglobin-free perfused rat livers were treated with carbon tetrachloride, chloroform, trichloroethylene and halothane by equilibrium of the perfusion medium with the varorous PHHCs. The resulting swelling of liver tissue, the potassium loss and the decrease of the perfusion rates were reduced by DEDTC to a different degree: The decrease of swelling, potassium loss and of the microcirculatory alteration by DEDTC was dose dependent in the case of carbon tetrachloride and halothane, whereas the effects of chloroform and trichloroethylene were not markedly influenced. Glutathione was mostly ineffective when given in similar doses. Pretreatment of rats with phenobarbital for 3 days increased itself swelling, K+-loss and reduction of perfusion rates, when the livers were perfused in absence of PHHCs. The effects of PHHCs in livers from pretreated rats were seldom greater but often lower than additive ones. Chiefly the effects of halothane were not markedly influenced by treatment of rats with phenobarbital. Isolated parenchymal liver cells were exposed to gas mixtures of O2, CO2 and PHHCs under controled conditions. Changes of the shape and staining of the cells were used for additional information. In view of these latter effects chloroform appeared as the most toxic and halothane as a nontoxic agent. DEDTC inhibits all effects of PHHCs demonstrated in isolated hepatocytes.", "contents": "[Inhibition by diethyldithiocarbamate (DEDTC) of acute hepatotoxic effects induced by polyhalogenated hydrocarbons (PHHC)]. Hemoglobin-free perfused rat livers were treated with carbon tetrachloride, chloroform, trichloroethylene and halothane by equilibrium of the perfusion medium with the varorous PHHCs. The resulting swelling of liver tissue, the potassium loss and the decrease of the perfusion rates were reduced by DEDTC to a different degree: The decrease of swelling, potassium loss and of the microcirculatory alteration by DEDTC was dose dependent in the case of carbon tetrachloride and halothane, whereas the effects of chloroform and trichloroethylene were not markedly influenced. Glutathione was mostly ineffective when given in similar doses. Pretreatment of rats with phenobarbital for 3 days increased itself swelling, K+-loss and reduction of perfusion rates, when the livers were perfused in absence of PHHCs. The effects of PHHCs in livers from pretreated rats were seldom greater but often lower than additive ones. Chiefly the effects of halothane were not markedly influenced by treatment of rats with phenobarbital. Isolated parenchymal liver cells were exposed to gas mixtures of O2, CO2 and PHHCs under controled conditions. Changes of the shape and staining of the cells were used for additional information. In view of these latter effects chloroform appeared as the most toxic and halothane as a nontoxic agent. DEDTC inhibits all effects of PHHCs demonstrated in isolated hepatocytes."} {"id": "PMID:178250", "title": "Studies of the hemopoietic microenvironment. VIII. Andrenergic and cholinergic innervation of the murine spleen.", "content": "Neurohistochemical techniques were used to confirm morphologically the distribution of adrenergic and cholinergic nerves to the splenic microvasculature. The results form the basis of this report. Using these methods, adrenergic innervation was observed only in the adventitia of arteries and arterioles. No cholinergic innervation was found in this site. No adrenergic or cholinergic innervation could be demonstrated to the channels of the red pulp, venules or veins. These data provided morphological evidence that in the murine spleen only splenic arteries and arterioles are innervated; and these have only an adrenergic innervation.", "contents": "Studies of the hemopoietic microenvironment. VIII. Andrenergic and cholinergic innervation of the murine spleen. Neurohistochemical techniques were used to confirm morphologically the distribution of adrenergic and cholinergic nerves to the splenic microvasculature. The results form the basis of this report. Using these methods, adrenergic innervation was observed only in the adventitia of arteries and arterioles. No cholinergic innervation was found in this site. No adrenergic or cholinergic innervation could be demonstrated to the channels of the red pulp, venules or veins. These data provided morphological evidence that in the murine spleen only splenic arteries and arterioles are innervated; and these have only an adrenergic innervation."} {"id": "PMID:178251", "title": "Steroid concentrations in cows with corticotropin-induced cystic ovarian follicles and the effect of prostaglandin F2alpha and indomethacin given by intrauterine injection.", "content": "In 7 instances, cystic ovarian follicles resulted when adrenocorticotropin (ACTH) was administered daily during the follicular phase of the estrous cycle in cows. Two cows given daily injections of hydrocortisone (cortisol) during the follicular phase of the estrous cycle did not develop cystic ovaries. Plasma concentrations of estradiol in cows with induced cystic ovarian follicles were similar to the peak values observed at estrus and were between 6 and 12 pg/ml. Progesterone concentrations in plasma of cows with cystic ovaries were low, between 1 and 2 ng/ml. Ovulation occurred when 2 cows were given human chorionic gonadotropin (HCG) during the period of ovarian cyst development with ACTH administration. Several days of administration of ACTH was required to cause cyst development. Ovulation occurred at the expected time in 1 cow when injections began on day 19, that is, late in the follicular period. In another cow, when treatment was stopped on day 3, after the expected time of estrus a delayed ovulation occurred. In 2 cows with induced cystic ovarian follicles, cyst atresia occurred spontaneously about day 13 to 17 of the cycle. In these cows, new follicular growth and ovulation followed (although delayed in 1 cow). The time of atresia of cystic follicles was not influenced by the intrauterine injection of 10 ml of sterile saline solution on days 8, 9, and 10 in 1 cow. When 5 mg of prostaglandin F2alpha in 10 ml of sterile saline solution was given (uterine injection) in 2 cows on days 8, 9, and 10, cyst atresia occurred earlier than the time of spontaneous atresia. Intrauterine administration of 100 mg of indomethacin in 10 ml of sterile saline solution daily for 13 or 14 days to 2 cows, starting on day 12 or 13 of the cycle, resulted in persistence of the induced cystic ovarian follicles. After cessation of indomethacin treatment, atresia of cysts followed and new follicular growth and ovulation occurred.", "contents": "Steroid concentrations in cows with corticotropin-induced cystic ovarian follicles and the effect of prostaglandin F2alpha and indomethacin given by intrauterine injection. In 7 instances, cystic ovarian follicles resulted when adrenocorticotropin (ACTH) was administered daily during the follicular phase of the estrous cycle in cows. Two cows given daily injections of hydrocortisone (cortisol) during the follicular phase of the estrous cycle did not develop cystic ovaries. Plasma concentrations of estradiol in cows with induced cystic ovarian follicles were similar to the peak values observed at estrus and were between 6 and 12 pg/ml. Progesterone concentrations in plasma of cows with cystic ovaries were low, between 1 and 2 ng/ml. Ovulation occurred when 2 cows were given human chorionic gonadotropin (HCG) during the period of ovarian cyst development with ACTH administration. Several days of administration of ACTH was required to cause cyst development. Ovulation occurred at the expected time in 1 cow when injections began on day 19, that is, late in the follicular period. In another cow, when treatment was stopped on day 3, after the expected time of estrus a delayed ovulation occurred. In 2 cows with induced cystic ovarian follicles, cyst atresia occurred spontaneously about day 13 to 17 of the cycle. In these cows, new follicular growth and ovulation followed (although delayed in 1 cow). The time of atresia of cystic follicles was not influenced by the intrauterine injection of 10 ml of sterile saline solution on days 8, 9, and 10 in 1 cow. When 5 mg of prostaglandin F2alpha in 10 ml of sterile saline solution was given (uterine injection) in 2 cows on days 8, 9, and 10, cyst atresia occurred earlier than the time of spontaneous atresia. Intrauterine administration of 100 mg of indomethacin in 10 ml of sterile saline solution daily for 13 or 14 days to 2 cows, starting on day 12 or 13 of the cycle, resulted in persistence of the induced cystic ovarian follicles. After cessation of indomethacin treatment, atresia of cysts followed and new follicular growth and ovulation occurred."} {"id": "PMID:178252", "title": "Pathogenesis of duck plague in the bursa of Fabricius, thymus, and spleen.", "content": "White Pekin ducks were inoculated orally with duck plague virus and killed at 24-hour intervals after inoculation. Spleen, thymus, and bursa of Fabricius were collected and examined by light, fluorescent, and electron microscopy. Necrosis of lymphocytes occurred in the bursa of Fabricius, thymus, splenic periarteriolar lymphoid sheath (T lymphocytes), and splenic germinal centers (B lymphocytes). Viral nucleocapsids were present in the karyoplasm of lymphocytes, but these cells necrotized before virions were formed. Periarteriolar reticular sheath cells and sinusoidal lining cells in the spleen, epithelial cells in Hassall's corpuscle of the thymus, epithelial cells between the cortex and medulla of the follicles in the bursa of Fabricius, and macrophages in all 3 tissues contained nucleocapsids in the nuclei and virions in cytoplasmic vacuoles before necrosis occurred.", "contents": "Pathogenesis of duck plague in the bursa of Fabricius, thymus, and spleen. White Pekin ducks were inoculated orally with duck plague virus and killed at 24-hour intervals after inoculation. Spleen, thymus, and bursa of Fabricius were collected and examined by light, fluorescent, and electron microscopy. Necrosis of lymphocytes occurred in the bursa of Fabricius, thymus, splenic periarteriolar lymphoid sheath (T lymphocytes), and splenic germinal centers (B lymphocytes). Viral nucleocapsids were present in the karyoplasm of lymphocytes, but these cells necrotized before virions were formed. Periarteriolar reticular sheath cells and sinusoidal lining cells in the spleen, epithelial cells in Hassall's corpuscle of the thymus, epithelial cells between the cortex and medulla of the follicles in the bursa of Fabricius, and macrophages in all 3 tissues contained nucleocapsids in the nuclei and virions in cytoplasmic vacuoles before necrosis occurred."} {"id": "PMID:178253", "title": "Precipitin response of cattle to commercial wart vaccine.", "content": "Fifty young bulls were given commercial wart vaccine upon their arrival at a bull stud establishment. The bulls were given 2 additional vaccinations 2 and 24 weeks later. The precipitin antibody response of these bulls to bovine papilloma virus was monitored. Antibody levels increased significantly, particularly after the 3rd vaccination was given at 24 weeks, but decreased markedly within 20 weeks after the last vaccination was given. These results demonstrated that formalin-inactivated bovine papilloma virus was capable of inducing precipitin antibody similar to infective bovine papilloma virus. Multiple, repeated vaccination provided the best serologic response.", "contents": "Precipitin response of cattle to commercial wart vaccine. Fifty young bulls were given commercial wart vaccine upon their arrival at a bull stud establishment. The bulls were given 2 additional vaccinations 2 and 24 weeks later. The precipitin antibody response of these bulls to bovine papilloma virus was monitored. Antibody levels increased significantly, particularly after the 3rd vaccination was given at 24 weeks, but decreased markedly within 20 weeks after the last vaccination was given. These results demonstrated that formalin-inactivated bovine papilloma virus was capable of inducing precipitin antibody similar to infective bovine papilloma virus. Multiple, repeated vaccination provided the best serologic response."} {"id": "PMID:178254", "title": "Speculations on neurogenic pulmonary edema (NPE).", "content": "Evidence suggests the following pathogenesis for neurogenic pulmonary edema. The initial phase results from a centrally mediated, massive, sympathetic discharge. This produces intense, generalized, but transient, vasoconstriction with a resultant shift of blood from the high-resistance systemic circulation to the lowresistance pulmonary circulation. Marked increases in pulmonary vascular pressures and marked increases in pulmonary blood volume then produce pulmonary edema because of the hydrostatic effect of increased pulmonary capillary pressure. In addition, pulmonary hypertension and hypervolemia injure pulmonary blood vessels, altering pulmonary capillary permeability and producing lung hemorrhage. After the transient systemic and pulmonary vascular hypertension subside, the patient is left with abnormal pulmonary capillary permeability, so that pulmonary edema persists in the face of normal hemodynamics and normal cardia function.", "contents": "Speculations on neurogenic pulmonary edema (NPE). Evidence suggests the following pathogenesis for neurogenic pulmonary edema. The initial phase results from a centrally mediated, massive, sympathetic discharge. This produces intense, generalized, but transient, vasoconstriction with a resultant shift of blood from the high-resistance systemic circulation to the lowresistance pulmonary circulation. Marked increases in pulmonary vascular pressures and marked increases in pulmonary blood volume then produce pulmonary edema because of the hydrostatic effect of increased pulmonary capillary pressure. In addition, pulmonary hypertension and hypervolemia injure pulmonary blood vessels, altering pulmonary capillary permeability and producing lung hemorrhage. After the transient systemic and pulmonary vascular hypertension subside, the patient is left with abnormal pulmonary capillary permeability, so that pulmonary edema persists in the face of normal hemodynamics and normal cardia function."} {"id": "PMID:178255", "title": "Immune status in lung cancer: effects of BCG immunotherapy.", "content": "Immunotherapy with bacille Calmette-Gu\u00e9rin (BCG) was administered according to a standard regimen to 23 patients with primary lung cancer who had completed conventional treatment, including surgery and/or radiation therapy. Five additional patients did not receive BCG. Skin tests and in vitro lymphocyte studies were performed serially at intervals for 12 months or until death. The aggregate of skin responses to nonmycobacterial antigens and lymphocyte responses to phytohemagglutinin and recall antigens increased only in the group of 7 patients with no clinically evident disease 12 months after the start of BCG administration. The group of 5 patients who did not receive BCG, but who remained clinically disease free, did not experience immunoenhancement, nor did BCG-treated patients with residual or recurrent malignancy. Patients who had received radiation therapy before BCG also did not experience immunoenhancement, but these patients also had recurrent or persistent disease. Enhancement of certain aspects of the immune response to within 1 SD of the response of a group of subjects with nonmalignant pulmonary disease was prognostic of a favorable clinical outcome at 12 months.", "contents": "Immune status in lung cancer: effects of BCG immunotherapy. Immunotherapy with bacille Calmette-Gu\u00e9rin (BCG) was administered according to a standard regimen to 23 patients with primary lung cancer who had completed conventional treatment, including surgery and/or radiation therapy. Five additional patients did not receive BCG. Skin tests and in vitro lymphocyte studies were performed serially at intervals for 12 months or until death. The aggregate of skin responses to nonmycobacterial antigens and lymphocyte responses to phytohemagglutinin and recall antigens increased only in the group of 7 patients with no clinically evident disease 12 months after the start of BCG administration. The group of 5 patients who did not receive BCG, but who remained clinically disease free, did not experience immunoenhancement, nor did BCG-treated patients with residual or recurrent malignancy. Patients who had received radiation therapy before BCG also did not experience immunoenhancement, but these patients also had recurrent or persistent disease. Enhancement of certain aspects of the immune response to within 1 SD of the response of a group of subjects with nonmalignant pulmonary disease was prognostic of a favorable clinical outcome at 12 months."} {"id": "PMID:178258", "title": "Fatal case of influenza pneumonia with suprainfection by multiple bacteria and Herpes simplex virus.", "content": "A case of influenza pneumonia is described in which death occurred from persistence of the influenza infection and suprainfection with two bacteria, Staphylococcus aureus and Escherichia coli, and another virus, Herpes simplex. Of additional interest were the observations that this overwhelming illness developed in a previously healthy person, that typical influenza virus particles were present in antemortem lung tissue, and that the patient died despite 6 days of extracorporeal membrane oxygenation and corticosteroids.", "contents": "Fatal case of influenza pneumonia with suprainfection by multiple bacteria and Herpes simplex virus. A case of influenza pneumonia is described in which death occurred from persistence of the influenza infection and suprainfection with two bacteria, Staphylococcus aureus and Escherichia coli, and another virus, Herpes simplex. Of additional interest were the observations that this overwhelming illness developed in a previously healthy person, that typical influenza virus particles were present in antemortem lung tissue, and that the patient died despite 6 days of extracorporeal membrane oxygenation and corticosteroids."} {"id": "PMID:178259", "title": "Paget's disease of the male breast: a collective review and case report.", "content": "A brief review of the world literature is presented, of which 19 cases are accepted as genuine Paget's disease of the male breast, and one new case is reported. Emphasis is put on early diagnosis by biopsy, and definite treatment by radical mastectomy.", "contents": "Paget's disease of the male breast: a collective review and case report. A brief review of the world literature is presented, of which 19 cases are accepted as genuine Paget's disease of the male breast, and one new case is reported. Emphasis is put on early diagnosis by biopsy, and definite treatment by radical mastectomy."} {"id": "PMID:178260", "title": "Gastric and extragastric leiomyoblastoma: report of six new cases with a review of the literature.", "content": "Six case reports of leiomyoblastoma are presented, five involving stomach, and one involving jejunum. The malignant potential of these tumors is questionable. The literature is summarized and the symptomatology, age and sex predominance commented upon. A brief pathological description is noted. The survival statistics, although unmeaningful at this time, are presented.", "contents": "Gastric and extragastric leiomyoblastoma: report of six new cases with a review of the literature. Six case reports of leiomyoblastoma are presented, five involving stomach, and one involving jejunum. The malignant potential of these tumors is questionable. The literature is summarized and the symptomatology, age and sex predominance commented upon. A brief pathological description is noted. The survival statistics, although unmeaningful at this time, are presented."} {"id": "PMID:178262", "title": "Granular cell myoblastoma of the lid: case report.", "content": "Granular cell myoblastoma, a tumor found commonly in the tongue and subcutaneous tissue, has rarely been reported in the orbital region. The second case of primary granular cell myoblastoma in the eyelid is reported.", "contents": "Granular cell myoblastoma of the lid: case report. Granular cell myoblastoma, a tumor found commonly in the tongue and subcutaneous tissue, has rarely been reported in the orbital region. The second case of primary granular cell myoblastoma in the eyelid is reported."} {"id": "PMID:178263", "title": "Abnormal guanosine 3', 5'-monophosphate during photoreceptor degeneration in the inherited retinal disorder of C3H/HeJ mice.", "content": "Elevated levels of guanosine 3'-5'-monophosphate (cyclic GMP) are associated with photoreceptor degeneration in the retina of C3H/HeJ mice. This abonormality has been shown to result from a deficiency in the activity of a receptor-specific cyclic GMP phosphodiesterase. The apparent susceptibility of photoreceptor cells to an abnormality in cyclic GMP metabolism suggests that cyclic GMP may play a role in photoreceptor function which is essential to the viability of these specialized cells.", "contents": "Abnormal guanosine 3', 5'-monophosphate during photoreceptor degeneration in the inherited retinal disorder of C3H/HeJ mice. Elevated levels of guanosine 3'-5'-monophosphate (cyclic GMP) are associated with photoreceptor degeneration in the retina of C3H/HeJ mice. This abonormality has been shown to result from a deficiency in the activity of a receptor-specific cyclic GMP phosphodiesterase. The apparent susceptibility of photoreceptor cells to an abnormality in cyclic GMP metabolism suggests that cyclic GMP may play a role in photoreceptor function which is essential to the viability of these specialized cells."} {"id": "PMID:178261", "title": "[Inflammatory pseudotumor of the lung in infancy (histiocytoma) (author's transl)].", "content": "A four year old boy with a clinical picture of acute pneumonia is presented. Antibiotic therapeutic improved the clinical and analytic symptomatology but a round, radiologic shadow persisted after three months of evolution. Thoracotomy was performed and by histopathologic examination histiocytoma of lung diagnosed. Literature is reviewed and the clinical, radiologic, pathologic and etiopathogenetic features are commented. These lesions should be considered as benign to avoid extensive resection.", "contents": "[Inflammatory pseudotumor of the lung in infancy (histiocytoma) (author's transl)]. A four year old boy with a clinical picture of acute pneumonia is presented. Antibiotic therapeutic improved the clinical and analytic symptomatology but a round, radiologic shadow persisted after three months of evolution. Thoracotomy was performed and by histopathologic examination histiocytoma of lung diagnosed. Literature is reviewed and the clinical, radiologic, pathologic and etiopathogenetic features are commented. These lesions should be considered as benign to avoid extensive resection."} {"id": "PMID:178267", "title": "Head and neck tumours in Rhodesia.", "content": "A retrospective 5-year study of head and neck tumours treated at a general hospital in Rhodesia and an attempted follow-up of the patients were undertaken in connection with the setting up of a joint head and neck clinic. The relevant data are outlined in this report.", "contents": "Head and neck tumours in Rhodesia. A retrospective 5-year study of head and neck tumours treated at a general hospital in Rhodesia and an attempted follow-up of the patients were undertaken in connection with the setting up of a joint head and neck clinic. The relevant data are outlined in this report."} {"id": "PMID:178269", "title": "[C14-variamycin content in normal and tumorous brain tissues of white rats].", "content": "Penetration of variamycin, a new antitumor antibiotic into the normal and tumor tissues of the brain of rats with multiform glioblastoma was investigated. The content of the C14-labeled antibiotic was determined radiometrically. The radioactive label penetrated into the normal and tumor tissues of the brain during the first hours after the drug administration. The level of the radioactivity in the tumor tissue was higher than that in the normal brain tissue during the whole period of the study. The greatest deviation in the contents of the radioactive label in the tumor and normal tissues was observed 2 and 3 hours after administration of the labeled antibiotic, i. e. 4.3 and 3.6 times respectively.", "contents": "[C14-variamycin content in normal and tumorous brain tissues of white rats]. Penetration of variamycin, a new antitumor antibiotic into the normal and tumor tissues of the brain of rats with multiform glioblastoma was investigated. The content of the C14-labeled antibiotic was determined radiometrically. The radioactive label penetrated into the normal and tumor tissues of the brain during the first hours after the drug administration. The level of the radioactivity in the tumor tissue was higher than that in the normal brain tissue during the whole period of the study. The greatest deviation in the contents of the radioactive label in the tumor and normal tissues was observed 2 and 3 hours after administration of the labeled antibiotic, i. e. 4.3 and 3.6 times respectively."} {"id": "PMID:178265", "title": "Fluorocitrate ototoxicity. A morphologic and cytochemical model for primary neural degeneration in the guinea pig cochlea.", "content": "Fluorocitrate, an inhibitor of the tricarboxylic acid cycle at the aconitase reaction, produces a time and dose related neural dystrophy in the guinea pig cochlea. There is direct inhibition of succinic dehydrogenase activity but not nicotinamide adenine dinucleotide dehydrogenase and cytochrome oxidase via cytochrome c activities. The dystrophic neural changes morphologically are similar to those noted in primary neural degeneration and neural presbycusis in man. Neural degeneration in aging appears to be the result of a dissociation of biochemical reactions preventing the proper utilization of organic fuel molecules for generation of energy and direct or indirect inhibition of respiration.", "contents": "Fluorocitrate ototoxicity. A morphologic and cytochemical model for primary neural degeneration in the guinea pig cochlea. Fluorocitrate, an inhibitor of the tricarboxylic acid cycle at the aconitase reaction, produces a time and dose related neural dystrophy in the guinea pig cochlea. There is direct inhibition of succinic dehydrogenase activity but not nicotinamide adenine dinucleotide dehydrogenase and cytochrome oxidase via cytochrome c activities. The dystrophic neural changes morphologically are similar to those noted in primary neural degeneration and neural presbycusis in man. Neural degeneration in aging appears to be the result of a dissociation of biochemical reactions preventing the proper utilization of organic fuel molecules for generation of energy and direct or indirect inhibition of respiration."} {"id": "PMID:178270", "title": "[Screening of antitumor antibiotics, formed by molds].", "content": "A system for screening fungal metabolites with cytotoxic activity against tumor cells is described and the results obtained using this system are discussed. It was found that 35.2 per cent of the strains isolated from uranium mines had a cytotoxic effect on the EAC cells in vitro. As for the strains isolated from other sources only 6.85 and 9.87 per cent of them inhibited the EAC cells in vitro. Five substances, i. e. vermiculline, PSX-I, Frequentine, bikaverin and duclauxin isolated from 227 evaluated cultures showed a strong inhibitory effect on the EAC cells and other tumors in vitro.", "contents": "[Screening of antitumor antibiotics, formed by molds]. A system for screening fungal metabolites with cytotoxic activity against tumor cells is described and the results obtained using this system are discussed. It was found that 35.2 per cent of the strains isolated from uranium mines had a cytotoxic effect on the EAC cells in vitro. As for the strains isolated from other sources only 6.85 and 9.87 per cent of them inhibited the EAC cells in vitro. Five substances, i. e. vermiculline, PSX-I, Frequentine, bikaverin and duclauxin isolated from 227 evaluated cultures showed a strong inhibitory effect on the EAC cells and other tumors in vitro."} {"id": "PMID:178266", "title": "Isolation of viruses and mycoplasmas from middle ear effusions: a review.", "content": "Reports of studies of middle ear effusions (MEE) obtained by needle aspiration are reviewed in this paper; viruses were isolated from 29 of 663 patients (4.4%) and respiratory syncytial virus was isolated most frequently (22 patients); only one mycoplasma, M. pneumoniae, was recovered from the MEE of 771 patients. Viruses were also sought from the throat or nasopharynx of 249 patients with MEE; 59 patients (23.7%) had a respiratory virus present. M. pneumoniae was isolated from the throat or nasopharynx in three of 116 patients. Although these results indicate that viruses and mycoplasmas are uncommonly found in effusions associated with acute or chronic otitis media, few studies have been attempted in recent years. The discovery of additional respiratory viruses and development of new techniques for isolation and identification of viruses indicate that the present results may be incomplete.", "contents": "Isolation of viruses and mycoplasmas from middle ear effusions: a review. Reports of studies of middle ear effusions (MEE) obtained by needle aspiration are reviewed in this paper; viruses were isolated from 29 of 663 patients (4.4%) and respiratory syncytial virus was isolated most frequently (22 patients); only one mycoplasma, M. pneumoniae, was recovered from the MEE of 771 patients. Viruses were also sought from the throat or nasopharynx of 249 patients with MEE; 59 patients (23.7%) had a respiratory virus present. M. pneumoniae was isolated from the throat or nasopharynx in three of 116 patients. Although these results indicate that viruses and mycoplasmas are uncommonly found in effusions associated with acute or chronic otitis media, few studies have been attempted in recent years. The discovery of additional respiratory viruses and development of new techniques for isolation and identification of viruses indicate that the present results may be incomplete."} {"id": "PMID:178272", "title": "[Sensitivity of pathogenic clostridia to antibiotics].", "content": "By the sensitivity levels of the gas infection causative agents, i. e. pathogenic Clostridia to antibiotics, the latter were conditionally divided into 4 groups. The 1st group included the most active antibiotics, such as tetracyclines,, penicillins, cephalosporins, rifampicin, 7-chlor-7-desoxylincomycin. Their minimum inhibitory and bactericidal concentrations did not usually exceed 2 gamma/ml. For most of the strains the inhibitory and bactericidal concentrations amounted to the tenth and hundredth fractions of gamma/ml. The antibiotics of the 2nd group, i. e. erythromycin, lincomycin,ristomycin and levomycetin inhibited multiplication and viability of pathogenic Clostridia in concentrations of 20 gamma/ml. Erythromycin was most active among them The 3rd group consisted of oleandomycin, novobiocin, geliomycin and azalomycin, the minimum inhibitory concentrations of them being 20 to 50 gamma/ml. The antibiotics of the 4th group, i. e. neomycin, monomycin, kanamycin, streptomycin, polymyxin and others affected pathogenic Clostridia at very high concentrations, amounting to the hundrenth and thousandth of gamma/ml.", "contents": "[Sensitivity of pathogenic clostridia to antibiotics]. By the sensitivity levels of the gas infection causative agents, i. e. pathogenic Clostridia to antibiotics, the latter were conditionally divided into 4 groups. The 1st group included the most active antibiotics, such as tetracyclines,, penicillins, cephalosporins, rifampicin, 7-chlor-7-desoxylincomycin. Their minimum inhibitory and bactericidal concentrations did not usually exceed 2 gamma/ml. For most of the strains the inhibitory and bactericidal concentrations amounted to the tenth and hundredth fractions of gamma/ml. The antibiotics of the 2nd group, i. e. erythromycin, lincomycin,ristomycin and levomycetin inhibited multiplication and viability of pathogenic Clostridia in concentrations of 20 gamma/ml. Erythromycin was most active among them The 3rd group consisted of oleandomycin, novobiocin, geliomycin and azalomycin, the minimum inhibitory concentrations of them being 20 to 50 gamma/ml. The antibiotics of the 4th group, i. e. neomycin, monomycin, kanamycin, streptomycin, polymyxin and others affected pathogenic Clostridia at very high concentrations, amounting to the hundrenth and thousandth of gamma/ml."} {"id": "PMID:178273", "title": "Sulfamethoxazole-trimethoprim-polymyxin therapy of serious multiply drug-resistant Serratia infections.", "content": "Nonpigmented multiply drug-resistant Serratia marcescens caused an extensive outbreak of infection at the Nashville Veterans Administration Hospital. Isolates were of one serotype resistant to all currently available antimicrobial agents for therapy of systemic infections except for occasional susceptibility to chloramphenicol and kanamycin. Frequently strains were susceptible to nalidixic acid, and all were susceptible to amikacin (BB-K8). Drug-resistant strains caused 130 infections, 12 bacteremias, and 7 infection-associated deaths. Combinations of antimicrobial agents were evaluated for synergism against Serratia strains from infected patients. \"Checkerboard\" isobolograms indicated in vitro static synergism between sulfamethoxazole, trimethoprim, and polymyxin (STP). Killing curves using clinically achievable concentrations of STP verified the bactericidal effect of STP against these strains. In a daily dosage of 1,600 mg of sulfamethoxazole and 320 mg of trimethoprim orally in combination with 100 to 300 mg of colistimethate parenterally, serum cidal levels at 1:8 or greater were achieved in five of six patients. Clinical improvement or microbiological cure was effected in four of six patients. STP may be potentially useful for selected Serratia infections for which single agents are unavailable or ineffective.", "contents": "Sulfamethoxazole-trimethoprim-polymyxin therapy of serious multiply drug-resistant Serratia infections. Nonpigmented multiply drug-resistant Serratia marcescens caused an extensive outbreak of infection at the Nashville Veterans Administration Hospital. Isolates were of one serotype resistant to all currently available antimicrobial agents for therapy of systemic infections except for occasional susceptibility to chloramphenicol and kanamycin. Frequently strains were susceptible to nalidixic acid, and all were susceptible to amikacin (BB-K8). Drug-resistant strains caused 130 infections, 12 bacteremias, and 7 infection-associated deaths. Combinations of antimicrobial agents were evaluated for synergism against Serratia strains from infected patients. \"Checkerboard\" isobolograms indicated in vitro static synergism between sulfamethoxazole, trimethoprim, and polymyxin (STP). Killing curves using clinically achievable concentrations of STP verified the bactericidal effect of STP against these strains. In a daily dosage of 1,600 mg of sulfamethoxazole and 320 mg of trimethoprim orally in combination with 100 to 300 mg of colistimethate parenterally, serum cidal levels at 1:8 or greater were achieved in five of six patients. Clinical improvement or microbiological cure was effected in four of six patients. STP may be potentially useful for selected Serratia infections for which single agents are unavailable or ineffective."} {"id": "PMID:178274", "title": "Metronidazole bioassay.", "content": "Urine from patients receiving metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitromidazole] orally or per vagina were subjected to paper chromatographic fractionation and examined for anticlostridial activity. Unmodified metronidazole and several metabolites were detected. These findings indicate that the clostridial bioassay may be limited in its applicability to the study of the pharmacodynamics of metronidazole as it does not differentiate between the parent substance and some of its metabolites. Moreover, some of the latter, although they possess antibacterial activity, may not have antiprotozoan activity.", "contents": "Metronidazole bioassay. Urine from patients receiving metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitromidazole] orally or per vagina were subjected to paper chromatographic fractionation and examined for anticlostridial activity. Unmodified metronidazole and several metabolites were detected. These findings indicate that the clostridial bioassay may be limited in its applicability to the study of the pharmacodynamics of metronidazole as it does not differentiate between the parent substance and some of its metabolites. Moreover, some of the latter, although they possess antibacterial activity, may not have antiprotozoan activity."} {"id": "PMID:178275", "title": "In vivo synergy between 6 beta-amidinopenicillanic acid derivatives and other antibiotics.", "content": "Both an oral and a parenteral form of a 6beta-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella, and Haemophilus species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the Staphylococcus aureus infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of Escherichia coli.", "contents": "In vivo synergy between 6 beta-amidinopenicillanic acid derivatives and other antibiotics. Both an oral and a parenteral form of a 6beta-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella, and Haemophilus species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the Staphylococcus aureus infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of Escherichia coli."} {"id": "PMID:178276", "title": "Effect of delayed evisceration on the microbial quality of meat.", "content": "The postomortem invasion of muscle and other tissues by bacteria from the intestinal tract was studied with the use of radioactive tracers. The injection of 14C-labeled bacteria or spores into the intestines of guinea pig carcasses within 24 h of death resulted in the rapid spread of 14C throughout carcasses. When live bacteria were injected along with the labeled cells, it was not possible to isolate viable organisms from the body tissues if the living animal had been exposed to the bacteria. It appears that animals are immune to their normal intestinal flora and that this immunity persists after death; thus passage of these bacteria into the lymphatic system does not necessarily result in the presence of live bacteria in carcass tissues. It therefore seems that a delay of up to 24 h before evisceration would not lead to deep tissue contamination of the carcass by organisms usually present in the intestines. Further evidence for this hypothesis was obtained by showing that muscle and lymph nodes from uneviscerated lamb carcasses hung for 24 h at 20 C remained sterile.", "contents": "Effect of delayed evisceration on the microbial quality of meat. The postomortem invasion of muscle and other tissues by bacteria from the intestinal tract was studied with the use of radioactive tracers. The injection of 14C-labeled bacteria or spores into the intestines of guinea pig carcasses within 24 h of death resulted in the rapid spread of 14C throughout carcasses. When live bacteria were injected along with the labeled cells, it was not possible to isolate viable organisms from the body tissues if the living animal had been exposed to the bacteria. It appears that animals are immune to their normal intestinal flora and that this immunity persists after death; thus passage of these bacteria into the lymphatic system does not necessarily result in the presence of live bacteria in carcass tissues. It therefore seems that a delay of up to 24 h before evisceration would not lead to deep tissue contamination of the carcass by organisms usually present in the intestines. Further evidence for this hypothesis was obtained by showing that muscle and lymph nodes from uneviscerated lamb carcasses hung for 24 h at 20 C remained sterile."} {"id": "PMID:178277", "title": "LevoDopa test and estrogen receptor assay in prognosticating responses of patients with advanced cancer of the breast to endocrine therapy.", "content": "The ability of L-dopa to arrest pain can be used to predict objective response of skeletal disease to endocrine ablation or additive therapy. In the present study, 43 patients with painful skeletal metastases were evaluated for the relief of pain by L-dopa, given 250 mg to 500 mg orally every 4 hours for 4 days. Sixteen of the 25 responders to L-dopa had objective response to either previous or later hormonal therapy while all the 18 non-responders did not benefit from endocrine ablation. The results of L-dopa responses also correlated well to the presence of absence of cytoplasmic ER in tumor. These results demonstrate that both tests (L-dopa and ER) are reliable indicators, one complimenting the other, in prognosticating response to endocrine therapy and should be used prior to hormone treatment. Alternative therapy should be considered for patients who are non-responders to the L-dopa test and/or whose tumors contain negligible ER. The long term therapeutic value of L-Dopa, however, is limited.", "contents": "LevoDopa test and estrogen receptor assay in prognosticating responses of patients with advanced cancer of the breast to endocrine therapy. The ability of L-dopa to arrest pain can be used to predict objective response of skeletal disease to endocrine ablation or additive therapy. In the present study, 43 patients with painful skeletal metastases were evaluated for the relief of pain by L-dopa, given 250 mg to 500 mg orally every 4 hours for 4 days. Sixteen of the 25 responders to L-dopa had objective response to either previous or later hormonal therapy while all the 18 non-responders did not benefit from endocrine ablation. The results of L-dopa responses also correlated well to the presence of absence of cytoplasmic ER in tumor. These results demonstrate that both tests (L-dopa and ER) are reliable indicators, one complimenting the other, in prognosticating response to endocrine therapy and should be used prior to hormone treatment. Alternative therapy should be considered for patients who are non-responders to the L-dopa test and/or whose tumors contain negligible ER. The long term therapeutic value of L-Dopa, however, is limited."} {"id": "PMID:178278", "title": "Hematuria and rectal bleeding in the child with Klippel and Trenaunay syndrome.", "content": "We have operated upon 588 patients with Klippel and Trenaunay syndrome. The underlying factor is a congenital malformation of the deep veins: agenesis, atresia or compression by fibrovascular bands of the popliteal, femoral or iliac veins. Of these 588 patients, 6 children between 15 months and 4 years of age had severe rectal bleeding and hematuria. One of these children died from massive bleeding of the rectum with septicemia. Another boy was saved by rectal resection and the last one by subtotal cystectomy. The important venogram shows an absence of the anterior venous pathway (superficial femoral vein) compensated by the abnormal development of 2 venous groups, the vein of the sciatic nerve and large veins along the external aspect of the inferior limb. These 2 venous groups penetrate into the pelvis by the sciatic and gluteal notches and terminate in the internal iliac vein which becomes enormous and has a very high flow. This overflow hinders drainage of the venous collateral from the rectum, the bladder and the vagina. The retro adductor vein, prolongated by the deep femoral vein, represents an anastomosis between the sciatic nerve vein and the common femoral vein. The surgeon must try to widen this pathway.", "contents": "Hematuria and rectal bleeding in the child with Klippel and Trenaunay syndrome. We have operated upon 588 patients with Klippel and Trenaunay syndrome. The underlying factor is a congenital malformation of the deep veins: agenesis, atresia or compression by fibrovascular bands of the popliteal, femoral or iliac veins. Of these 588 patients, 6 children between 15 months and 4 years of age had severe rectal bleeding and hematuria. One of these children died from massive bleeding of the rectum with septicemia. Another boy was saved by rectal resection and the last one by subtotal cystectomy. The important venogram shows an absence of the anterior venous pathway (superficial femoral vein) compensated by the abnormal development of 2 venous groups, the vein of the sciatic nerve and large veins along the external aspect of the inferior limb. These 2 venous groups penetrate into the pelvis by the sciatic and gluteal notches and terminate in the internal iliac vein which becomes enormous and has a very high flow. This overflow hinders drainage of the venous collateral from the rectum, the bladder and the vagina. The retro adductor vein, prolongated by the deep femoral vein, represents an anastomosis between the sciatic nerve vein and the common femoral vein. The surgeon must try to widen this pathway."} {"id": "PMID:178279", "title": "The rhabdoviruses of Entamoeba histolytica and Entamoeba invadens.", "content": "Rhabdoviruses have been described in plants, arthropods and vertebrates including man. Members of the group are of agricultural, veterinary and medical importance. The presence of a rhabdovirus in Entamoeba histolytica and Entamoeba invadens is the first record of their existence within protozoa. The morphology of this virus is described and its significance discussed, in relation to a possible lysogenic state and pathogenecity of Entamoeba species.", "contents": "The rhabdoviruses of Entamoeba histolytica and Entamoeba invadens. Rhabdoviruses have been described in plants, arthropods and vertebrates including man. Members of the group are of agricultural, veterinary and medical importance. The presence of a rhabdovirus in Entamoeba histolytica and Entamoeba invadens is the first record of their existence within protozoa. The morphology of this virus is described and its significance discussed, in relation to a possible lysogenic state and pathogenecity of Entamoeba species."} {"id": "PMID:178280", "title": "The susceptibility of isolated guts from various species of mosquito to some arboviruses.", "content": "Isolated guts cultured in vitro from Aedes Aeaegypti and Ae. togoi were more susceptible to infection by SIN, SF, CHIK and WN viruses than tissue similarly cultured from Anopheles gambiae and An. stephensi. Langat TP 64, a tick-borne virus, failed to infect any of the cultured mosquito tissues.", "contents": "The susceptibility of isolated guts from various species of mosquito to some arboviruses. Isolated guts cultured in vitro from Aedes Aeaegypti and Ae. togoi were more susceptible to infection by SIN, SF, CHIK and WN viruses than tissue similarly cultured from Anopheles gambiae and An. stephensi. Langat TP 64, a tick-borne virus, failed to infect any of the cultured mosquito tissues."} {"id": "PMID:178281", "title": "Technetium stannous pyrophosphate myocardial scintigrams in the recognition of myocardial infarction in patients undergoing coronary artery revascularization.", "content": "Myocardial imaging using technetium 99m stannous pyrophosphate (99mTc-PYP) has been utilized preoperatively and three to five days postoperatively to detect myocardial infarction in 48 patients undergoing aortocoronary bypass grafting, including 7 having valve replacement (5 aortic, 2 mitral) in addition to revascularization. In the total group of patients operated on there were 3 deaths (6%). Preoperatively, 26 patients had unstable angina and 10 had severe left main coronary artery disease. Eleven of the 48 (23%) were women. ECG and enzyme-proved infarctions occurred in 6 of the 48 patients (12%), but the addition of 99mTc-PYP myocardial imaging demonstrated scintigraphic evidence of infarction in 15 patients (31%), including 2 who died in the operating room. The 99mTc-PYP myocardial imaging technique, which has proved safe, simple, and relatively inexpensive in these patients, suggests that the incidence of infarction after coronary bypass operations is somewhat higher than has been previously recognized from just ECG and enzyme changes. This technique also has been of value in helping to exclude myocardial infarction in difficult clinical situations such as postoperative arrhythmias and the postpericardiotomy syndrome.", "contents": "Technetium stannous pyrophosphate myocardial scintigrams in the recognition of myocardial infarction in patients undergoing coronary artery revascularization. Myocardial imaging using technetium 99m stannous pyrophosphate (99mTc-PYP) has been utilized preoperatively and three to five days postoperatively to detect myocardial infarction in 48 patients undergoing aortocoronary bypass grafting, including 7 having valve replacement (5 aortic, 2 mitral) in addition to revascularization. In the total group of patients operated on there were 3 deaths (6%). Preoperatively, 26 patients had unstable angina and 10 had severe left main coronary artery disease. Eleven of the 48 (23%) were women. ECG and enzyme-proved infarctions occurred in 6 of the 48 patients (12%), but the addition of 99mTc-PYP myocardial imaging demonstrated scintigraphic evidence of infarction in 15 patients (31%), including 2 who died in the operating room. The 99mTc-PYP myocardial imaging technique, which has proved safe, simple, and relatively inexpensive in these patients, suggests that the incidence of infarction after coronary bypass operations is somewhat higher than has been previously recognized from just ECG and enzyme changes. This technique also has been of value in helping to exclude myocardial infarction in difficult clinical situations such as postoperative arrhythmias and the postpericardiotomy syndrome."} {"id": "PMID:178282", "title": "Carcinoma of the lung: results of treatment over ten years.", "content": "Mediastinal lymph node dissection in conjunction with pulmonary resection was performed on 437 patients with bronchogenic carcinoma at the University of Michigan Medical Center from 1959 to 1969. The absolute five- and ten-year survival rates for patients undergoing curative resection were 36.2 and 14.4%, respectively. The five-year survival of those without nodal metastases was 49.3%, and it was 31.1% in patients with hilar metastases only. The five-year survival of patients with mediastinal metastases who received radiation therapy was 23.1%. Of the 193 patients with squamous cell carcinoma, 43% lived five years free from disease. The five-year survival of patients undergoing resection who had no hilar lymph node metastases was 53%, and it was 47.5% in those with hilar metastases only. The five-year survival in patients with mediastinal metastases who received postoperative irradiation was 34.4%.", "contents": "Carcinoma of the lung: results of treatment over ten years. Mediastinal lymph node dissection in conjunction with pulmonary resection was performed on 437 patients with bronchogenic carcinoma at the University of Michigan Medical Center from 1959 to 1969. The absolute five- and ten-year survival rates for patients undergoing curative resection were 36.2 and 14.4%, respectively. The five-year survival of those without nodal metastases was 49.3%, and it was 31.1% in patients with hilar metastases only. The five-year survival of patients with mediastinal metastases who received radiation therapy was 23.1%. Of the 193 patients with squamous cell carcinoma, 43% lived five years free from disease. The five-year survival of patients undergoing resection who had no hilar lymph node metastases was 53%, and it was 47.5% in those with hilar metastases only. The five-year survival in patients with mediastinal metastases who received postoperative irradiation was 34.4%."} {"id": "PMID:178283", "title": "[Inhibition of 3', 5'-cyclic AMP phosphodiesterase in the guinea pig lung by a new anti-allergic: 10-(3-quinuclidinylmethyl) phenothiazine (LM 209)].", "content": "The action of a new antiallergic agent, 10-(3-quinuclidinylmethyl) phenothiazine or LM 209, on cAMP phosphodiesterase (PDE) was studied on a guinea-pig lung preparation and compared with that of other compounds such as cromoglycate (I), dexamethasone (II), dexchlorpheniramine (III), promethazine (IV) and theophylline (V). Compounds I, IV and V are competitive inhibitors whereas LM 209 and compound III are non competitive inhibitors of PDE. Compound II is practically inactive on the enzyme. Compounds III and V produce an inhibition of equal intensity, independently of the substrate concentration. Compounds I and IV are more active on PDE with low affinity than on PDE with strong affinity, whereas it is the contrary with LM 209. The mechanism of action of LM 209 at the pulmonary level is discussed in the light of these findings.", "contents": "[Inhibition of 3', 5'-cyclic AMP phosphodiesterase in the guinea pig lung by a new anti-allergic: 10-(3-quinuclidinylmethyl) phenothiazine (LM 209)]. The action of a new antiallergic agent, 10-(3-quinuclidinylmethyl) phenothiazine or LM 209, on cAMP phosphodiesterase (PDE) was studied on a guinea-pig lung preparation and compared with that of other compounds such as cromoglycate (I), dexamethasone (II), dexchlorpheniramine (III), promethazine (IV) and theophylline (V). Compounds I, IV and V are competitive inhibitors whereas LM 209 and compound III are non competitive inhibitors of PDE. Compound II is practically inactive on the enzyme. Compounds III and V produce an inhibition of equal intensity, independently of the substrate concentration. Compounds I and IV are more active on PDE with low affinity than on PDE with strong affinity, whereas it is the contrary with LM 209. The mechanism of action of LM 209 at the pulmonary level is discussed in the light of these findings."} {"id": "PMID:178284", "title": "An investigation of the effects of a pyridyl and a piperidyl 1, 3-dioxolane derivative on neuromuscular transmission.", "content": "2-(4'-pyridyl)-1,3-dioxolane methiodide (KCL-301-14) and 2-(1'-methyl-4' piperidyl)-1,3-dioxolane hydroiodide (KCL-301-39) facilitated the force of contraction in low doses and blocked it in higher doses in the in vivo cat soleus muscle preparation. Both drugs in the cat also reversed d-tubocurarine and succinylcholine blockade, produced post-drug repetitive activity, blocked post-tetanic potentiation (PTP), had no direct muscle affect and reversed the PTP suppression caused by d-tubocurarine and succinylcholine. In the rat phrenic nerve-diaphragm and the chick biventer cervicis preparations in vitro, facilitation, then blockade of the contraction were seen as concentrations increased. However, KCL-301-14 reversed d-tubocurarine and increased succinylcholine blockades in the rat and chick. KCl-301-39 increased both d-tubocurarine and succinylcholine blockades in the rat and chick. The different effects seen in the cat vs. the rat and chick with these drugs are probably due to species variation.", "contents": "An investigation of the effects of a pyridyl and a piperidyl 1, 3-dioxolane derivative on neuromuscular transmission. 2-(4'-pyridyl)-1,3-dioxolane methiodide (KCL-301-14) and 2-(1'-methyl-4' piperidyl)-1,3-dioxolane hydroiodide (KCL-301-39) facilitated the force of contraction in low doses and blocked it in higher doses in the in vivo cat soleus muscle preparation. Both drugs in the cat also reversed d-tubocurarine and succinylcholine blockade, produced post-drug repetitive activity, blocked post-tetanic potentiation (PTP), had no direct muscle affect and reversed the PTP suppression caused by d-tubocurarine and succinylcholine. In the rat phrenic nerve-diaphragm and the chick biventer cervicis preparations in vitro, facilitation, then blockade of the contraction were seen as concentrations increased. However, KCL-301-14 reversed d-tubocurarine and increased succinylcholine blockades in the rat and chick. KCl-301-39 increased both d-tubocurarine and succinylcholine blockades in the rat and chick. The different effects seen in the cat vs. the rat and chick with these drugs are probably due to species variation."} {"id": "PMID:178285", "title": "Dialysis in renal failure casued by amyloidosis of familial Mediterranean fever. A report of ten cases.", "content": "Ten unselected patients with renal failure casued by amyloidosis associated with FMF were treated by regular hemodialysis therapy from 1969 to 1974. They were compared to age-matched control patients treated by hemodialysis in the same unit during the same period, who were suffering from renal failure caused by other disease. Mortality in FMF and control patients was 30% with no significant difference in mean survival, shunt life, serum albumin or hemoglobin levels between the two groups. There was no significant difference in blood pressure measured predialysis or postdialysis in patients with FMF or in controls. The synthetic ACTH stimulation test showed adequate or elevated adrenocortical function. It is concluded that life can be prolonged up to 3 1/2 years by hemodialysis in renal failure caused by amyloidosis complicating FMF, and that renal failure casued by FMF is not a contraindication to regular hemodialysis therapy.", "contents": "Dialysis in renal failure casued by amyloidosis of familial Mediterranean fever. A report of ten cases. Ten unselected patients with renal failure casued by amyloidosis associated with FMF were treated by regular hemodialysis therapy from 1969 to 1974. They were compared to age-matched control patients treated by hemodialysis in the same unit during the same period, who were suffering from renal failure caused by other disease. Mortality in FMF and control patients was 30% with no significant difference in mean survival, shunt life, serum albumin or hemoglobin levels between the two groups. There was no significant difference in blood pressure measured predialysis or postdialysis in patients with FMF or in controls. The synthetic ACTH stimulation test showed adequate or elevated adrenocortical function. It is concluded that life can be prolonged up to 3 1/2 years by hemodialysis in renal failure caused by amyloidosis complicating FMF, and that renal failure casued by FMF is not a contraindication to regular hemodialysis therapy."} {"id": "PMID:178286", "title": "[Pseudohypohyperparathyroidism or Frame's pseudohypoparathyroidism type I].", "content": "Case report of a girl with fibrous osteitis lesions associated with clinical and biological symptoms of pseudo-hypoparathyroidism: hypocalcemia, hyperphosphoremia, absence of increase of phosphaturia (urine phosphate level) and especially of cyclic AMP after parathormone injection, high serum parathormone level. Similar cases described in literature are shortly analyzed. The genetic, pathogenic and nosologic problems of such an association are reviewed.", "contents": "[Pseudohypohyperparathyroidism or Frame's pseudohypoparathyroidism type I]. Case report of a girl with fibrous osteitis lesions associated with clinical and biological symptoms of pseudo-hypoparathyroidism: hypocalcemia, hyperphosphoremia, absence of increase of phosphaturia (urine phosphate level) and especially of cyclic AMP after parathormone injection, high serum parathormone level. Similar cases described in literature are shortly analyzed. The genetic, pathogenic and nosologic problems of such an association are reviewed."} {"id": "PMID:178287", "title": "Recorded and reported sleep in chronic primary insomnia.", "content": "Sleep polygraph and questionnaire data of 18 chronic primary insomniacs were compared with those of 18 age- and sex-matched controls. The insomniacs had significantly longer sleep latencies, less total sleep, less sleep efficiency, more terminal wake time, and less delta sleep. There were significant discrepancies between the insomniacs' and controls' subjective assessments of their sleep and the sleep-polygraph data, but in opposite directions. The insomniacs' recorded sleep also showed more night-to-night variability than that of the controls. However, the controls, in contrast to the insomniacs, reported sleeping worse in the laboratory than at home. Significant differences between insomnia subtypes validly reflected the insomniacs' subjective complaints and were generally in accord with expectations based on them.", "contents": "Recorded and reported sleep in chronic primary insomnia. Sleep polygraph and questionnaire data of 18 chronic primary insomniacs were compared with those of 18 age- and sex-matched controls. The insomniacs had significantly longer sleep latencies, less total sleep, less sleep efficiency, more terminal wake time, and less delta sleep. There were significant discrepancies between the insomniacs' and controls' subjective assessments of their sleep and the sleep-polygraph data, but in opposite directions. The insomniacs' recorded sleep also showed more night-to-night variability than that of the controls. However, the controls, in contrast to the insomniacs, reported sleeping worse in the laboratory than at home. Significant differences between insomnia subtypes validly reflected the insomniacs' subjective complaints and were generally in accord with expectations based on them."} {"id": "PMID:178288", "title": "[The \"greifswald-therapy-model\" for carcinoma of the cervix uteri for clinical testing of the cancer-multistep-therapy after M. von Ardenne (author's transl)].", "content": "The results of a preliminary study of the cancer-Multistep-Therapy (C.M.T.) (so called \"The Greifswald-Modell\") are reported. This Greifswald-Therapy-Model has been developed by hitherto existing experiences in the clinical test of the C.M.T. 4 patients with carcinoma uteri T2bNOMO to T2bNOMO level epithelium-carcinomas histologically verified showed after a preoperative treatment with C.M.T. and cantactradiatio (60CO) under the employment of a reduced dose of radios (1/2 to 1/3 of the pretherapy used in this clinic or 1/4 to 1/5 of the tumor dose) a complete regression of the tumor-specific changes. In the surgical specimen won after 4-7 weeks after C.M.T., carcinoma could not be detected either macroscopically or microscopically. Patients with a good therapy -- compatibility show a liberty of relapse with an increase in weight and an excellent physical and psychical health two year after C.M.T. This preliminary study shows the capability of the well - chosen therapy-model for the clinical test of the therapy-effect of the C.M.T. and it urgently demands to carry on with adequate alternate rows by including other conventional therapy schemes and other kinds of tumor to estimate definitively the effect of the C.M.T. in the tumor therapy.", "contents": "[The \"greifswald-therapy-model\" for carcinoma of the cervix uteri for clinical testing of the cancer-multistep-therapy after M. von Ardenne (author's transl)]. The results of a preliminary study of the cancer-Multistep-Therapy (C.M.T.) (so called \"The Greifswald-Modell\") are reported. This Greifswald-Therapy-Model has been developed by hitherto existing experiences in the clinical test of the C.M.T. 4 patients with carcinoma uteri T2bNOMO to T2bNOMO level epithelium-carcinomas histologically verified showed after a preoperative treatment with C.M.T. and cantactradiatio (60CO) under the employment of a reduced dose of radios (1/2 to 1/3 of the pretherapy used in this clinic or 1/4 to 1/5 of the tumor dose) a complete regression of the tumor-specific changes. In the surgical specimen won after 4-7 weeks after C.M.T., carcinoma could not be detected either macroscopically or microscopically. Patients with a good therapy -- compatibility show a liberty of relapse with an increase in weight and an excellent physical and psychical health two year after C.M.T. This preliminary study shows the capability of the well - chosen therapy-model for the clinical test of the therapy-effect of the C.M.T. and it urgently demands to carry on with adequate alternate rows by including other conventional therapy schemes and other kinds of tumor to estimate definitively the effect of the C.M.T. in the tumor therapy."} {"id": "PMID:178289", "title": "Human adenohypophysis in Nelson syndrome. Ultrastructural and clinical study.", "content": "The manifestations that comprise the disease known as Nelson syndrome are pituitary hyperplasia and cutaneous hyperpigmentation, which sometimes follow bilateral adrenalectomy, in patients with hypercortisolism. We present a comprehensive endocrinologic, structural study of a patient in whom the evidence obtained supports the hypotheses that: (a) the primary disorder in this form of hypercortisolism is probably hypothalamic; (b) the hyperplasia of the adenohypophysis, following adrenalectomy, is closely associated with lowered plasma cortisol levels; and (c) the cillular hyperplasia in the adenohypophysis involves primarily the corticotroph, a cell believed to be associated with the secretion of adrenocorticotrophic hormone and melanocyte-stimulating hormone.", "contents": "Human adenohypophysis in Nelson syndrome. Ultrastructural and clinical study. The manifestations that comprise the disease known as Nelson syndrome are pituitary hyperplasia and cutaneous hyperpigmentation, which sometimes follow bilateral adrenalectomy, in patients with hypercortisolism. We present a comprehensive endocrinologic, structural study of a patient in whom the evidence obtained supports the hypotheses that: (a) the primary disorder in this form of hypercortisolism is probably hypothalamic; (b) the hyperplasia of the adenohypophysis, following adrenalectomy, is closely associated with lowered plasma cortisol levels; and (c) the cillular hyperplasia in the adenohypophysis involves primarily the corticotroph, a cell believed to be associated with the secretion of adrenocorticotrophic hormone and melanocyte-stimulating hormone."} {"id": "PMID:178290", "title": "Mixed tumors of the salivary glands. Growth pattern and recurrence.", "content": "In 112 patients with mixed tumors of the salivary glands, 94 tumors were located in parotid glands, 11 in submandibular salivary glands, and 7 in monor palatal salivary glands. Capsular ingrowth, a characteristic growth pattern, may explain the frequency of multilobulation and capsular defects in these tumors, particularly those of long standing. The capsular thickness, the extent of fibrosis with stromal hyalinization, and the degree of lymphocytic infiltration within and around the capsule, were associated with cellularity of the tumors. Thus, 69% of the hypocellular neoplasms had incomplete capsules, and only 13% showed moderate to substantial lymphocytic infiltration; corresponding figures for hypercellular tumors were 22% and 42%, respectively. Of the recurrent lesions, 61% were hypocellular; 11% of the hypercellular tumors recurred. Incomplete resection, hypocellularity, and incomplete encapsulation were considered to be the major factors in recurrence.", "contents": "Mixed tumors of the salivary glands. Growth pattern and recurrence. In 112 patients with mixed tumors of the salivary glands, 94 tumors were located in parotid glands, 11 in submandibular salivary glands, and 7 in monor palatal salivary glands. Capsular ingrowth, a characteristic growth pattern, may explain the frequency of multilobulation and capsular defects in these tumors, particularly those of long standing. The capsular thickness, the extent of fibrosis with stromal hyalinization, and the degree of lymphocytic infiltration within and around the capsule, were associated with cellularity of the tumors. Thus, 69% of the hypocellular neoplasms had incomplete capsules, and only 13% showed moderate to substantial lymphocytic infiltration; corresponding figures for hypercellular tumors were 22% and 42%, respectively. Of the recurrent lesions, 61% were hypocellular; 11% of the hypercellular tumors recurred. Incomplete resection, hypocellularity, and incomplete encapsulation were considered to be the major factors in recurrence."} {"id": "PMID:178291", "title": "Gigantic cystosarcoma phyllodes in a man with gynecomastia.", "content": "A 70-year-old man had a breast tumor for 50 years. The tumor, which weighed 8.6 kg, proved to be a malignant cystosarcoma phyllodes. It was successfully removed by a simple mastectomy with low axillary dissection, and a skin graft was performed. The lesion was associated with gynecomastia, and it is believed to have represented a cystosarcomatous transformation of a giant fibroadenoma.", "contents": "Gigantic cystosarcoma phyllodes in a man with gynecomastia. A 70-year-old man had a breast tumor for 50 years. The tumor, which weighed 8.6 kg, proved to be a malignant cystosarcoma phyllodes. It was successfully removed by a simple mastectomy with low axillary dissection, and a skin graft was performed. The lesion was associated with gynecomastia, and it is believed to have represented a cystosarcomatous transformation of a giant fibroadenoma."} {"id": "PMID:178292", "title": "[Histoautoradiographic and biochemical study of the transport of atherogenic lipoproteins in the vascular wall].", "content": "Transport of serous pre-beta and beta-lipopropeins (beta-LP) labeled by C14 protein and by C14 lipid into the wall of the aorta was studied histoautoradiographically and biochemically. The aortas of healthy rabbits and rabbits wuth experimental atherosclerosis were perfused in vitro with a medium containing rabbit pre-beta and beta-LP during 6 hours. After perfusion the mark was identified histoautoradiographically in all layers of the aorta. The presence of gradient in distribution of the mark from the inner layers of the aortas towards the outward part of the media indicated that the process of infiltration of the wall of the LP vessel was caused by their penetration from the lumen of the aorta. Nonuniformity in distribution of LP penetrated into the atherosclerotic aorta was noted, which was considered in connection with the changes occurred in the connective tissue of the wall of the aorta in the process of atherogenesis. Results of both morphological and biochemical investigations confirm an increased permeability of the aorta wall for LP in atherosclerosis and also substantiate the assumption about penetration of pre-beta and beta-LP into the wall of the vessel as a whole particle.", "contents": "[Histoautoradiographic and biochemical study of the transport of atherogenic lipoproteins in the vascular wall]. Transport of serous pre-beta and beta-lipopropeins (beta-LP) labeled by C14 protein and by C14 lipid into the wall of the aorta was studied histoautoradiographically and biochemically. The aortas of healthy rabbits and rabbits wuth experimental atherosclerosis were perfused in vitro with a medium containing rabbit pre-beta and beta-LP during 6 hours. After perfusion the mark was identified histoautoradiographically in all layers of the aorta. The presence of gradient in distribution of the mark from the inner layers of the aortas towards the outward part of the media indicated that the process of infiltration of the wall of the LP vessel was caused by their penetration from the lumen of the aorta. Nonuniformity in distribution of LP penetrated into the atherosclerotic aorta was noted, which was considered in connection with the changes occurred in the connective tissue of the wall of the aorta in the process of atherogenesis. Results of both morphological and biochemical investigations confirm an increased permeability of the aorta wall for LP in atherosclerosis and also substantiate the assumption about penetration of pre-beta and beta-LP into the wall of the vessel as a whole particle."} {"id": "PMID:178293", "title": "[Structural-metabolic characteristics of the myocardium in acute hemorrhage and hyperbaric oxygenation].", "content": "Histochemical and pathomorphological changes in the myocardium in acute loss of blood and hyperbaric oxygenation were investigated in experiments on 130 white rats. It was established that acute loss of blood brought about an activation of phosphorylase, a decrease in the content of glycogen, an inhibition of the activity of cytochrome oxidase and succinic dehydrogenase in the myocardium. Foci of dystrophy were formed in the subendocaridal zone of the two ventricles and septum. Oxygenobarotherapy contributed to normalization of the level of activity of enzymes, preservation of glycogen, reduced the extent of manifestation of dystrophic changes in myocardiocytes. Hyperbaric oxygenation of healthy animals led to changes in the enzymatic activity in the myocardium. Dystrophic changes were noted in individual myocardiocytes. The data obtained testify to a direct influence of oxygen on metabolism of the myocardial cells.", "contents": "[Structural-metabolic characteristics of the myocardium in acute hemorrhage and hyperbaric oxygenation]. Histochemical and pathomorphological changes in the myocardium in acute loss of blood and hyperbaric oxygenation were investigated in experiments on 130 white rats. It was established that acute loss of blood brought about an activation of phosphorylase, a decrease in the content of glycogen, an inhibition of the activity of cytochrome oxidase and succinic dehydrogenase in the myocardium. Foci of dystrophy were formed in the subendocaridal zone of the two ventricles and septum. Oxygenobarotherapy contributed to normalization of the level of activity of enzymes, preservation of glycogen, reduced the extent of manifestation of dystrophic changes in myocardiocytes. Hyperbaric oxygenation of healthy animals led to changes in the enzymatic activity in the myocardium. Dystrophic changes were noted in individual myocardiocytes. The data obtained testify to a direct influence of oxygen on metabolism of the myocardial cells."} {"id": "PMID:178294", "title": "[The histoenzymology of arterial walls under normal conditions and during the development of atherosclerosis].", "content": "Investigation of enzymes of the vascular wall in atherosclerosis in man and in experiment should include biochemical studies in combination with histochemical control. It is most probable that the total activity of enzymes in the vascular wall in atherosclerosis depends upon the functional state of smooth-muscle cells. The character of changes in the activity of enzymes in the arteries susceptible to atherosclerosis makes it possible to prognose disturbances in metabolism of the vascular wall and partially to explain the sequency of the development of the atherosclerotic process.", "contents": "[The histoenzymology of arterial walls under normal conditions and during the development of atherosclerosis]. Investigation of enzymes of the vascular wall in atherosclerosis in man and in experiment should include biochemical studies in combination with histochemical control. It is most probable that the total activity of enzymes in the vascular wall in atherosclerosis depends upon the functional state of smooth-muscle cells. The character of changes in the activity of enzymes in the arteries susceptible to atherosclerosis makes it possible to prognose disturbances in metabolism of the vascular wall and partially to explain the sequency of the development of the atherosclerotic process."} {"id": "PMID:178295", "title": "Granular cell myoblastoma of the cervical trachea.", "content": "Only five granular cell myoblastomas affecting the cervical trachea have been previously reported. Two of these tumors appear to be primary lesions of the trachea, while the remaining three appear to involve it only secondarily. We report a case of an intraluminal granular cell myoblastoma arising from the right tracheal wall in a 45-year-old woman. The tumor extended into the partition wall between trachea and esophagus. Treatment was by surgical excision of the tumor and the involved tracheal ring. The patient was free of recurrence one year after treatment.", "contents": "Granular cell myoblastoma of the cervical trachea. Only five granular cell myoblastomas affecting the cervical trachea have been previously reported. Two of these tumors appear to be primary lesions of the trachea, while the remaining three appear to involve it only secondarily. We report a case of an intraluminal granular cell myoblastoma arising from the right tracheal wall in a 45-year-old woman. The tumor extended into the partition wall between trachea and esophagus. Treatment was by surgical excision of the tumor and the involved tracheal ring. The patient was free of recurrence one year after treatment."} {"id": "PMID:178296", "title": "Facial diplegia.", "content": "Sudden facial diplegia or recurrent facial palsy is a rare occurrence, and may be the only symptom indicative of a systemic illness. Two patients had this condition in the absence of Guillain-Barr\u00e9-Strohl syndrome.", "contents": "Facial diplegia. Sudden facial diplegia or recurrent facial palsy is a rare occurrence, and may be the only symptom indicative of a systemic illness. Two patients had this condition in the absence of Guillain-Barr\u00e9-Strohl syndrome."} {"id": "PMID:178297", "title": "[The fructose induced \"glycogenosis\". II. Histochemical studies of glycogen metabolism in rat liver after fructose overload and similar diets (author's transl)].", "content": "Feeding of fructose for 7 days has been morphometrically shown to induce a SER-reduction and an accumulation of glycogen in rat liver cells. This hypothetical model \"glycogenosis\" is investigated with histochemical methods. Rats are given a solution of 60% fructose in water as only nutritional source. Controls are given a solution of 60% glucose in water, an isocaloric Altromin-R-standard diet and an Altromin-R-standard diet ad libitum. Reversion of fructose induced metabolic changes is investigated by a 7 days fructose diet followed by an 1-4 days Altromin-R-standard diet ad libitum. Glycogen and glycogen metabolizing enzymes are demonstrated after a 7 days diet and in the course of an 1-7 days fructose diet. Feeding of fructose leads to a high glycogen content, combined with a high activity of glycogen-phosphorylase and glucose-6-phosphatase in the liver parenchyma. Glycogen-synthetase activity increases during the first 4 days and then it drops to a low level. A pathological alteration of liver cell metabolism seems to be improbable, for all fructose induced changes are reversibel after 2 days of Altromin-R-standard diet. Glucose-6-phosphatase, as a marker-enzyme of the smooth endoplasmatic reticulum, is discussed to become activated by disruption of SER membranes due to fructose.", "contents": "[The fructose induced \"glycogenosis\". II. Histochemical studies of glycogen metabolism in rat liver after fructose overload and similar diets (author's transl)]. Feeding of fructose for 7 days has been morphometrically shown to induce a SER-reduction and an accumulation of glycogen in rat liver cells. This hypothetical model \"glycogenosis\" is investigated with histochemical methods. Rats are given a solution of 60% fructose in water as only nutritional source. Controls are given a solution of 60% glucose in water, an isocaloric Altromin-R-standard diet and an Altromin-R-standard diet ad libitum. Reversion of fructose induced metabolic changes is investigated by a 7 days fructose diet followed by an 1-4 days Altromin-R-standard diet ad libitum. Glycogen and glycogen metabolizing enzymes are demonstrated after a 7 days diet and in the course of an 1-7 days fructose diet. Feeding of fructose leads to a high glycogen content, combined with a high activity of glycogen-phosphorylase and glucose-6-phosphatase in the liver parenchyma. Glycogen-synthetase activity increases during the first 4 days and then it drops to a low level. A pathological alteration of liver cell metabolism seems to be improbable, for all fructose induced changes are reversibel after 2 days of Altromin-R-standard diet. Glucose-6-phosphatase, as a marker-enzyme of the smooth endoplasmatic reticulum, is discussed to become activated by disruption of SER membranes due to fructose."} {"id": "PMID:178324", "title": "Is atheroma a reversible lesion?", "content": "In this review atherogenic factors are discussed in relation to the possibility of regression. Evidence for regression of human lesions comes mainly from postwar studies and observations on persons with chronic wasting diseases. The entry, exit and effects of lipids in the arterial wass are considered as important factors which might determine regression. A variety of experiments in different animals which have been done in order to study regression are described. Some involve cholesterol feeding and withdrawal, others are concerned with the effects of hyperoxia and drugs. It is concluded that certain forms of atheroma can be induced to regress.", "contents": "Is atheroma a reversible lesion? In this review atherogenic factors are discussed in relation to the possibility of regression. Evidence for regression of human lesions comes mainly from postwar studies and observations on persons with chronic wasting diseases. The entry, exit and effects of lipids in the arterial wass are considered as important factors which might determine regression. A variety of experiments in different animals which have been done in order to study regression are described. Some involve cholesterol feeding and withdrawal, others are concerned with the effects of hyperoxia and drugs. It is concluded that certain forms of atheroma can be induced to regress."} {"id": "PMID:178325", "title": "Clofibrate-induced low density liporotein elevation. Therapeutic implications and treatment by colestipol resin.", "content": "Plasma lipid and lipoprotein responses to clofibrate were assessed in fifteen hypertriglyceridemic patients for the purpose of ascertaining low-density lipoprotein (LDL) changes. Subjects were grouped into either Type IV (11) or IIB (4) subgroups according to initial LDL level. Clofibrate was without effect on LDL in the IIB group, but consistent, often large, elevations were noted in Type IV cases (mean increase, 37.6%, P less than 0.001). In the IIB subgroup, addition of the bile-acid sequestrant, colestipol, lowered LDL (27.8%, P less 0.02) and total cholesterol (21.3%, P less 0.01) below pre-treatment values. In the Type IV subgroup, LDL fell to 19.5% above baseline (P great than 0.05). Significant LDL elevations induced by clofibrate in three of six subjects were restored to initial levels. In both groups, triglycerides and very-low density lipoproteins (VLDL) were not affected. The efficacy of colestipol in reducing LDL levels, expressed as either absolute or percentage reductions, increased as a function of increasing post-clofibrate LDL concentration (r = 0.84, P less than 0.001). In these subjects the level of LDL after treatment with clofibrate depended upon their LDL level prior to drug therapy, the effect of clofibrate on this level, and lipoprotein phenotype. Thus colestipol was most effective in IIB subjects, Type IV subjects with the lowest baseline VLDL and hence reciprocally highest LDL, and Type IV individuals who exhibited the largest LDL induction by clofibrate. The reported ineffectiveness of clofibrate on mortality and morbidity in patients with established coronary heart disease might be related to elevations and infrequent reductions of LDL. From the perspective of lipoprotein lowering, the combination with colestipol appears more favorable.", "contents": "Clofibrate-induced low density liporotein elevation. Therapeutic implications and treatment by colestipol resin. Plasma lipid and lipoprotein responses to clofibrate were assessed in fifteen hypertriglyceridemic patients for the purpose of ascertaining low-density lipoprotein (LDL) changes. Subjects were grouped into either Type IV (11) or IIB (4) subgroups according to initial LDL level. Clofibrate was without effect on LDL in the IIB group, but consistent, often large, elevations were noted in Type IV cases (mean increase, 37.6%, P less than 0.001). In the IIB subgroup, addition of the bile-acid sequestrant, colestipol, lowered LDL (27.8%, P less 0.02) and total cholesterol (21.3%, P less 0.01) below pre-treatment values. In the Type IV subgroup, LDL fell to 19.5% above baseline (P great than 0.05). Significant LDL elevations induced by clofibrate in three of six subjects were restored to initial levels. In both groups, triglycerides and very-low density lipoproteins (VLDL) were not affected. The efficacy of colestipol in reducing LDL levels, expressed as either absolute or percentage reductions, increased as a function of increasing post-clofibrate LDL concentration (r = 0.84, P less than 0.001). In these subjects the level of LDL after treatment with clofibrate depended upon their LDL level prior to drug therapy, the effect of clofibrate on this level, and lipoprotein phenotype. Thus colestipol was most effective in IIB subjects, Type IV subjects with the lowest baseline VLDL and hence reciprocally highest LDL, and Type IV individuals who exhibited the largest LDL induction by clofibrate. The reported ineffectiveness of clofibrate on mortality and morbidity in patients with established coronary heart disease might be related to elevations and infrequent reductions of LDL. From the perspective of lipoprotein lowering, the combination with colestipol appears more favorable."} {"id": "PMID:178326", "title": "Lipoprotein concentrations in serum and in biopsy samples of arterial intima: a quantitive comparison.", "content": "Lipoprotein concentrations were compared in serum and in samples of arterial intima obtained during cardiovascular surgery. The interval between blood sampling and surgery did not exceed 48 hours. Apolipoproteins B and C, the major proteins of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) respectivity, were detectable by immuno-assay in all arterial specimens. Highly significant positive correlations existed between the levels of lipoproteins in the intima and in serum. In patients with elevated serum VLDL levels (Type IV hyperlipoproteinaemia) arterial concentrations of apolipoproteins B and C were increased about two-fold; in those with raised LDL levels in serum (Type II), with or without concomitant elevation of VLDL levels, the concentration of apolipoprotein B was increased almost 5-fold in the arterial intima. The arterial wall therefore contains lipoproteins or their immunologically-similar metabolites at concentrations which are determined in part by serum lipoprotein levels.", "contents": "Lipoprotein concentrations in serum and in biopsy samples of arterial intima: a quantitive comparison. Lipoprotein concentrations were compared in serum and in samples of arterial intima obtained during cardiovascular surgery. The interval between blood sampling and surgery did not exceed 48 hours. Apolipoproteins B and C, the major proteins of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) respectivity, were detectable by immuno-assay in all arterial specimens. Highly significant positive correlations existed between the levels of lipoproteins in the intima and in serum. In patients with elevated serum VLDL levels (Type IV hyperlipoproteinaemia) arterial concentrations of apolipoproteins B and C were increased about two-fold; in those with raised LDL levels in serum (Type II), with or without concomitant elevation of VLDL levels, the concentration of apolipoprotein B was increased almost 5-fold in the arterial intima. The arterial wall therefore contains lipoproteins or their immunologically-similar metabolites at concentrations which are determined in part by serum lipoprotein levels."} {"id": "PMID:178330", "title": "Relation between extent of coronary artery disease and severity of hyperlipoproteinaemia.", "content": "Lipoprotein analyses were performed in 133 male patients and were correlated with the coronary arteriographic findings. The prevalence of hyperlipoproteinaemia was significantly higher in those patients with coronary artery disease (P less than 0-02). In addition, the more extensive the degree of coronary artery pathology the higher were the plasma concentrations of total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol. Hyperlipoproteinaemia was more prevalent in the younger patients with coronary artery disease (P less than 0-02).", "contents": "Relation between extent of coronary artery disease and severity of hyperlipoproteinaemia. Lipoprotein analyses were performed in 133 male patients and were correlated with the coronary arteriographic findings. The prevalence of hyperlipoproteinaemia was significantly higher in those patients with coronary artery disease (P less than 0-02). In addition, the more extensive the degree of coronary artery pathology the higher were the plasma concentrations of total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol. Hyperlipoproteinaemia was more prevalent in the younger patients with coronary artery disease (P less than 0-02)."} {"id": "PMID:178327", "title": "Triglyceride accumulation in cultured human fibroblasts: the effects of hypertriglyceridemic serum.", "content": "Cultures of human diploid fibroblasts were shown to accumulate elevated levels of intracellular triglyceride when grown in medium supplemented with sera from patients with endogenous hypertriglyceridemia (Type IV hyperlipoproteinemia). Time course studies indicated cell triglyceride levels reached maxium in 6 to 12 hours. Isotopic studies indicated that the source of the accumulated cell triglyceride was serum triglyceride, and that most of the triglyceride was taken up without hydrolysis. Triglyceride was not significantly removed by trypsinization or extensive washing. The accumulated triglyceride was also demonostrated to be metabolized, as indicated by conversion to phospholipids and free fatty acids. Increasing concentrations of hypertriglyceridemic serum in the medium resulted in increasing cell triglyceride levels. However, increasing amounts of normal serum did not result in comparable cell triglyceride accumulation. Intracellular triglyceride accumulation seemed to correlate with levels of hypertriglyceridemic serum triglyceride, whether this serum was present at equivalent concentrations or normalized to triglyceride levels equivalent to normal serum. It is concluded that elevated serum triglyceride levels can result in intracellular triglyceride accumulation even in the absence of lipolytic activity.", "contents": "Triglyceride accumulation in cultured human fibroblasts: the effects of hypertriglyceridemic serum. Cultures of human diploid fibroblasts were shown to accumulate elevated levels of intracellular triglyceride when grown in medium supplemented with sera from patients with endogenous hypertriglyceridemia (Type IV hyperlipoproteinemia). Time course studies indicated cell triglyceride levels reached maxium in 6 to 12 hours. Isotopic studies indicated that the source of the accumulated cell triglyceride was serum triglyceride, and that most of the triglyceride was taken up without hydrolysis. Triglyceride was not significantly removed by trypsinization or extensive washing. The accumulated triglyceride was also demonostrated to be metabolized, as indicated by conversion to phospholipids and free fatty acids. Increasing concentrations of hypertriglyceridemic serum in the medium resulted in increasing cell triglyceride levels. However, increasing amounts of normal serum did not result in comparable cell triglyceride accumulation. Intracellular triglyceride accumulation seemed to correlate with levels of hypertriglyceridemic serum triglyceride, whether this serum was present at equivalent concentrations or normalized to triglyceride levels equivalent to normal serum. It is concluded that elevated serum triglyceride levels can result in intracellular triglyceride accumulation even in the absence of lipolytic activity."} {"id": "PMID:178328", "title": "Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man.", "content": "The plasma concentration of unesterified and esterified cholesterol within very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins have been examined in relation to the metabolism and pool size of cholesterol in normal and hyperlipidaemic subjects. Cholesterol metabolism was assessed as faecal endogenous neutral and acidic steroid excretion, a 2-pool model of cholesterol turnover, and in vitro plasma cholesterol esterifying activity. VLDL total cholesterol (TC) concentration was positively correlated with cholesterol turnover, endogenous neutral steroid excretion, bile acid excretion and the absolute rate of plasma cholestrol esterification. The correlations with cholesterol turnover and neutral steroid excretion, but not that with bile acid excretion, remained significant when these were corrected for their relationships to body weight. LDL-TC was negatively correlated with the fractional rate of plasma cholesterol esterification and, in subjects with primary type IIa hyperlipoproteinaemia, also with the rate constant for cholesterol elimination from the rapidly exchanging cholesterol pool. No correlation was found between LDL-TC concentration and bile acid excretion. HDL-TC concentration was negatively correlated with both the rapidly and slowly exchanging pools of tissue cholesterol, after correction for their relationships to body weight and adiposity. In contrast, cholesterol pool sizes were not correlated with the concentration of VLDL or LDL-TC; nor was there any relationship to plasma cholesterol esterifying activity. No correlation was found between the relative proportions of unesterified cholesterol within any lipoprotein fraction and either the pool size or metabolism of cholesterol. These findings accord with previous reports of enhanced cholesterol metabolism in subjects with elevated VLDL concentrations and of impaired plasma LDL and cholesterol clearance in patients with primary type IIa hyperlipoproteinaemia. The demonstration that HDL-TC concentration is negatively correlated with body cholesterol pool size supports in vitro evidence for a role of HDL IN TISSUE CHOLESTEROL CLEARENCE.", "contents": "Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man. The plasma concentration of unesterified and esterified cholesterol within very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins have been examined in relation to the metabolism and pool size of cholesterol in normal and hyperlipidaemic subjects. Cholesterol metabolism was assessed as faecal endogenous neutral and acidic steroid excretion, a 2-pool model of cholesterol turnover, and in vitro plasma cholesterol esterifying activity. VLDL total cholesterol (TC) concentration was positively correlated with cholesterol turnover, endogenous neutral steroid excretion, bile acid excretion and the absolute rate of plasma cholestrol esterification. The correlations with cholesterol turnover and neutral steroid excretion, but not that with bile acid excretion, remained significant when these were corrected for their relationships to body weight. LDL-TC was negatively correlated with the fractional rate of plasma cholesterol esterification and, in subjects with primary type IIa hyperlipoproteinaemia, also with the rate constant for cholesterol elimination from the rapidly exchanging cholesterol pool. No correlation was found between LDL-TC concentration and bile acid excretion. HDL-TC concentration was negatively correlated with both the rapidly and slowly exchanging pools of tissue cholesterol, after correction for their relationships to body weight and adiposity. In contrast, cholesterol pool sizes were not correlated with the concentration of VLDL or LDL-TC; nor was there any relationship to plasma cholesterol esterifying activity. No correlation was found between the relative proportions of unesterified cholesterol within any lipoprotein fraction and either the pool size or metabolism of cholesterol. These findings accord with previous reports of enhanced cholesterol metabolism in subjects with elevated VLDL concentrations and of impaired plasma LDL and cholesterol clearance in patients with primary type IIa hyperlipoproteinaemia. The demonstration that HDL-TC concentration is negatively correlated with body cholesterol pool size supports in vitro evidence for a role of HDL IN TISSUE CHOLESTEROL CLEARENCE."} {"id": "PMID:178329", "title": "Changing relative proportions of apolipoproteins CII and CIII of very low density lipoproteins in hypertriglyceridaemia.", "content": "The very low density lipoproteins (VLDL) of fasting serum from subjects with normo- and hypertriglyceridaemia (Type IV and V) were separated into subfractions by density gradient centrifugation. The tetramethylurea (TMU)- soluble apolipoproteins were separated by polyacrylamide gel electrophoresis and the relative proportions of apo CII and CIIIs determined. There were highly significant correlations between the concentration of VLDL triglycerides and apo CII (r---0.92), apo CIII1 (r=+0.88) and the ratio apo CII/apo CIII1 (r= --0.94). It was suggested that the decreasing ratio apo CII/CIII1 with increasing triglyceride levels might cause a resistance to lipoprotein lipase and therefore a defect lipolysis of VLDL based upon a changed ratio apo CII/apo CII1 might be part of the pathogenesis of the hypertriglyceridaemia.", "contents": "Changing relative proportions of apolipoproteins CII and CIII of very low density lipoproteins in hypertriglyceridaemia. The very low density lipoproteins (VLDL) of fasting serum from subjects with normo- and hypertriglyceridaemia (Type IV and V) were separated into subfractions by density gradient centrifugation. The tetramethylurea (TMU)- soluble apolipoproteins were separated by polyacrylamide gel electrophoresis and the relative proportions of apo CII and CIIIs determined. There were highly significant correlations between the concentration of VLDL triglycerides and apo CII (r---0.92), apo CIII1 (r=+0.88) and the ratio apo CII/apo CIII1 (r= --0.94). It was suggested that the decreasing ratio apo CII/CIII1 with increasing triglyceride levels might cause a resistance to lipoprotein lipase and therefore a defect lipolysis of VLDL based upon a changed ratio apo CII/apo CII1 might be part of the pathogenesis of the hypertriglyceridaemia."} {"id": "PMID:178333", "title": "Studies on antistreptolysin O activity generated in serum by microorganisms.", "content": "An antistreptolysin factor (ASF) was generated in normal human serum by the growth of Staph, aureus and Pseud, aeruginosa. Alpha toxin producing strains of the former were usually positive but activity was not restricted to such strains. Positive strains produce cholesterol esterase which was obtained from DEAE-cellulose column fractions of 18 h broth cultures. Antistreptolysin factor develops slowly in serum, being maximal between the 5th and 10th days and is associated with alterations and disappearance of beta lipoproteins on gel electrophoresis. Activity also appeared in beta lipoproteins precipitated from normal serum with dextran sulphate and redissolved in nutrient broth before inoculation with Staph, aureus. The slow appearance of antistreptolysin activity in serum appears to be due to an esterase inhibitor which is present in high concentrations in some sera. Activity is also modified by the production of a staphylococcal fraction capable of binding to the antistreptolysin factor and reducing its activity. It is suggested that antistreptolysin factor which can be demonstrated in small amounts in normal human serum represents a readily available non-specific defence mechanism capable of binding to certain bacterial products and possible to other foreign protein molecules.", "contents": "Studies on antistreptolysin O activity generated in serum by microorganisms. An antistreptolysin factor (ASF) was generated in normal human serum by the growth of Staph, aureus and Pseud, aeruginosa. Alpha toxin producing strains of the former were usually positive but activity was not restricted to such strains. Positive strains produce cholesterol esterase which was obtained from DEAE-cellulose column fractions of 18 h broth cultures. Antistreptolysin factor develops slowly in serum, being maximal between the 5th and 10th days and is associated with alterations and disappearance of beta lipoproteins on gel electrophoresis. Activity also appeared in beta lipoproteins precipitated from normal serum with dextran sulphate and redissolved in nutrient broth before inoculation with Staph, aureus. The slow appearance of antistreptolysin activity in serum appears to be due to an esterase inhibitor which is present in high concentrations in some sera. Activity is also modified by the production of a staphylococcal fraction capable of binding to the antistreptolysin factor and reducing its activity. It is suggested that antistreptolysin factor which can be demonstrated in small amounts in normal human serum represents a readily available non-specific defence mechanism capable of binding to certain bacterial products and possible to other foreign protein molecules."} {"id": "PMID:178334", "title": "Detection of macrophages in atherosclerotic lesions with cytochrome oxidase.", "content": "The anaerobic metabolism of the arterial wall allows macrophages to be demonstrated therein by the cytochrome oxidase histochemical method. Monocytes (macrophages) in human fatty streaks (WHO grade I) or fibrofatty (WHO grade II) human atherosclerotic lesions are normally confined to subendothelial regions. Lesions complicated by ulceration, mural thrombosis or intimal haemorrhage (WHO grade III) showed numerous monocytes (macrophages) around newly-formed capillaries in focal areas of organization. By contrast with grades I and II atherosclerotic lesions, macrophages in lipid granulomas induced by subcutaneous injection of cholesterol oleate are more numerous and distributed throughout the lesion. The slow or absent resorption of lipid from atheromatous lesions may in part result from the paucity of macrophages therein.", "contents": "Detection of macrophages in atherosclerotic lesions with cytochrome oxidase. The anaerobic metabolism of the arterial wall allows macrophages to be demonstrated therein by the cytochrome oxidase histochemical method. Monocytes (macrophages) in human fatty streaks (WHO grade I) or fibrofatty (WHO grade II) human atherosclerotic lesions are normally confined to subendothelial regions. Lesions complicated by ulceration, mural thrombosis or intimal haemorrhage (WHO grade III) showed numerous monocytes (macrophages) around newly-formed capillaries in focal areas of organization. By contrast with grades I and II atherosclerotic lesions, macrophages in lipid granulomas induced by subcutaneous injection of cholesterol oleate are more numerous and distributed throughout the lesion. The slow or absent resorption of lipid from atheromatous lesions may in part result from the paucity of macrophages therein."} {"id": "PMID:178335", "title": "Further observations on subacute sclerosing encephalitis in adult hamsters: the effects of intranasal infections with Langat virus, measles virus and SSPE-measles virus.", "content": "Passage by i.c. inoculations of suckling hamsters enhanced the virulence for adult hamsters of Langat virus (TP21), neurotropic strain of measles virus (HNT) and SSPE-measles virus (HBS), not only for i.c. infections but also for intranasal instillations. The various viral strains passaged in hamsters showed a great similarity of behaviour including the ability of producing in a proportion of apparently unaffected survivors a subacute sclerosing encephalitis, leading to atrophy of parts of the brain especially the rhinencephalon. When large groups of animals were used for transmission experiments it became obvious that within one week after intranasal exposure, all the hamsters either died or became clinically affected, or did not show signs of disease but developed acute inflammatory brain lessions. tlater on, between 2-6 weeks following inoculations only 90% of hamsters were affected with either overt signs of disease or subacute brain lesions, suggesting that in about 10% of hamsters the initial infection did not progress further and that in these animals the early brain lesions disappeared. Passage levels, irrespective of the virus used, did not influence the total numbers of infected hamsters but showed a significant effect on the mortality in TP21 and HNT infections where the number of dead and clinically affected increased in the higher passes. In these higher passes the number of survivors with subacute brain lesions decreased. In SSPE-measles virus the number of clinically affected hamsters and those surviving but developing brain lesions remained constant throughout. Vacuolated neurons were present in the brains of hamsters that survived one of the above 3 viral infections. They were seen beginning from 6 weeks after infection only in animals that developed subacute sclerosing lesions and were most commonly found in the amygdaloid nuclei and in the pyriform cortex. There was a dramatic increase in the number of brains with vacuolated neurons in hamsters infected with the high viral passes; however, in the 36th hamster passage of TP21 no vacuolated neurons were present but the total number of survivors was small, the majority had no brain lesions and none had subacute sclerosing changes.", "contents": "Further observations on subacute sclerosing encephalitis in adult hamsters: the effects of intranasal infections with Langat virus, measles virus and SSPE-measles virus. Passage by i.c. inoculations of suckling hamsters enhanced the virulence for adult hamsters of Langat virus (TP21), neurotropic strain of measles virus (HNT) and SSPE-measles virus (HBS), not only for i.c. infections but also for intranasal instillations. The various viral strains passaged in hamsters showed a great similarity of behaviour including the ability of producing in a proportion of apparently unaffected survivors a subacute sclerosing encephalitis, leading to atrophy of parts of the brain especially the rhinencephalon. When large groups of animals were used for transmission experiments it became obvious that within one week after intranasal exposure, all the hamsters either died or became clinically affected, or did not show signs of disease but developed acute inflammatory brain lessions. tlater on, between 2-6 weeks following inoculations only 90% of hamsters were affected with either overt signs of disease or subacute brain lesions, suggesting that in about 10% of hamsters the initial infection did not progress further and that in these animals the early brain lesions disappeared. Passage levels, irrespective of the virus used, did not influence the total numbers of infected hamsters but showed a significant effect on the mortality in TP21 and HNT infections where the number of dead and clinically affected increased in the higher passes. In these higher passes the number of survivors with subacute brain lesions decreased. In SSPE-measles virus the number of clinically affected hamsters and those surviving but developing brain lesions remained constant throughout. Vacuolated neurons were present in the brains of hamsters that survived one of the above 3 viral infections. They were seen beginning from 6 weeks after infection only in animals that developed subacute sclerosing lesions and were most commonly found in the amygdaloid nuclei and in the pyriform cortex. There was a dramatic increase in the number of brains with vacuolated neurons in hamsters infected with the high viral passes; however, in the 36th hamster passage of TP21 no vacuolated neurons were present but the total number of survivors was small, the majority had no brain lesions and none had subacute sclerosing changes."} {"id": "PMID:178336", "title": "The ineffectiveness of coumarin treatment on thermal oedema of macrophage-free rats.", "content": "The administration of silica prevents coumarin-stimulated lysis of accumulated abnormal protein. This impairs the resolution of thermal oedema which is normally increased with coumarin administration. Evidence suggests that there is a rapid differentiation and infiltration of monocytes into the tissues and that these are selectively retained. This is aided by coumarin which increases tissue permeability. Coumarin also injures the vascular endothelium of some vessels, allowing extra protein and fluid into the tissues. Death of recently differentiated macrophages and subsequent release of their lysosomal contents into the extra-cellular spaces may be responsible for the changes in serum enzyme levels. It would seem that macrophages are the only cells in which coumarin stimulates increased phagocytosis, enzyme production and proteolysis.", "contents": "The ineffectiveness of coumarin treatment on thermal oedema of macrophage-free rats. The administration of silica prevents coumarin-stimulated lysis of accumulated abnormal protein. This impairs the resolution of thermal oedema which is normally increased with coumarin administration. Evidence suggests that there is a rapid differentiation and infiltration of monocytes into the tissues and that these are selectively retained. This is aided by coumarin which increases tissue permeability. Coumarin also injures the vascular endothelium of some vessels, allowing extra protein and fluid into the tissues. Death of recently differentiated macrophages and subsequent release of their lysosomal contents into the extra-cellular spaces may be responsible for the changes in serum enzyme levels. It would seem that macrophages are the only cells in which coumarin stimulates increased phagocytosis, enzyme production and proteolysis."} {"id": "PMID:178337", "title": "Experimental infection of monkeys with viruses of the tick-borne encephalitis complex: degenerative cerebellar lesions following inapparent forms of the disease or recovery from clinical encephalitis.", "content": "Rhesus, patas and vervet monkeys were infected i.c. or i.n. with three viruses of the tick-borne encephalitis complex (TBE) as follows: Turkish tick-borne encephalitis virus (TTE), Louping-ill virus and Central European tick-borne encephalitis virus (CETE). The incidence of overt clinical signs of disease varied according to the virus that was used for the inoculations. TTE proved to be more pathogenic for monkeys than the other two members of the complex, whilst CETE was the least pathogenic. Injections of specific antiserum soon after infection tended to increase both the incidence of clinical signs and the moratlity. A proportion of animals with inapparent infections and a number of monkeys that recovered from the acute phase of the disease developed degenerative lesions in the cerebellum, often superimposed on the involuting inflammatory changes. The changes affected either a few only or many folia of the cerebellum and consisted of neuronal and spongy degeneration of the Purkinje and granular layers, usually accompanied by marked astrocytic proliferation and hypertrophy in the granular and molecular layers.", "contents": "Experimental infection of monkeys with viruses of the tick-borne encephalitis complex: degenerative cerebellar lesions following inapparent forms of the disease or recovery from clinical encephalitis. Rhesus, patas and vervet monkeys were infected i.c. or i.n. with three viruses of the tick-borne encephalitis complex (TBE) as follows: Turkish tick-borne encephalitis virus (TTE), Louping-ill virus and Central European tick-borne encephalitis virus (CETE). The incidence of overt clinical signs of disease varied according to the virus that was used for the inoculations. TTE proved to be more pathogenic for monkeys than the other two members of the complex, whilst CETE was the least pathogenic. Injections of specific antiserum soon after infection tended to increase both the incidence of clinical signs and the moratlity. A proportion of animals with inapparent infections and a number of monkeys that recovered from the acute phase of the disease developed degenerative lesions in the cerebellum, often superimposed on the involuting inflammatory changes. The changes affected either a few only or many folia of the cerebellum and consisted of neuronal and spongy degeneration of the Purkinje and granular layers, usually accompanied by marked astrocytic proliferation and hypertrophy in the granular and molecular layers."} {"id": "PMID:178338", "title": "Enzyme-immunoassays for antibodies in measles, cytomegalovirus infections and after rubella vaccination.", "content": "Enzyme-immunoassays using an indirect method with alkaline phosphatase conjugated antiglobulins were satisfactory for detection of antibody to Measles and Cytomegalovirus. The antigen was passively adsorbed to polystyrene micro-harmagglutination plates for the assays. IgM antibody to Rubella was also detected by enzyme-immunoassay at 7 and 28 days after vaccination in a person who had negative Rubella serology before vaccination. IgG antibody was detected at those times in another patient who had positive Rubella serology prior to vaccination. The enzyme immunoassays appear to have the potential for routine laboratory use for virological diagnosis.", "contents": "Enzyme-immunoassays for antibodies in measles, cytomegalovirus infections and after rubella vaccination. Enzyme-immunoassays using an indirect method with alkaline phosphatase conjugated antiglobulins were satisfactory for detection of antibody to Measles and Cytomegalovirus. The antigen was passively adsorbed to polystyrene micro-harmagglutination plates for the assays. IgM antibody to Rubella was also detected by enzyme-immunoassay at 7 and 28 days after vaccination in a person who had negative Rubella serology before vaccination. IgG antibody was detected at those times in another patient who had positive Rubella serology prior to vaccination. The enzyme immunoassays appear to have the potential for routine laboratory use for virological diagnosis."} {"id": "PMID:178339", "title": "Lysosomal hydrolases of the epidermis. 5. Variation with depth in the cow snout.", "content": "The activity of twelve acid hydrolases has been measured in serial horizontal sections of cow snout epidermis. The majority of these enzymes showed a clear peak in the basal and lower spinous cell layers; acid phosphatase, however, was found mainly in the keratinizing zone. These findings suggest that two discrete populations of lysosomes may occur in epidermis. Those present in the lower layers possess a typical pattern of hydrolase activity and probably correspond to the 'orthodox' lysosomes observed by electron microscopy techniques, whereas those found in the keratinizing zone possess an unusual hydrolase profile and may correspond to the bodies identified morphologically as keratinosomes (Odland bodies, membrane-coating granules).", "contents": "Lysosomal hydrolases of the epidermis. 5. Variation with depth in the cow snout. The activity of twelve acid hydrolases has been measured in serial horizontal sections of cow snout epidermis. The majority of these enzymes showed a clear peak in the basal and lower spinous cell layers; acid phosphatase, however, was found mainly in the keratinizing zone. These findings suggest that two discrete populations of lysosomes may occur in epidermis. Those present in the lower layers possess a typical pattern of hydrolase activity and probably correspond to the 'orthodox' lysosomes observed by electron microscopy techniques, whereas those found in the keratinizing zone possess an unusual hydrolase profile and may correspond to the bodies identified morphologically as keratinosomes (Odland bodies, membrane-coating granules)."} {"id": "PMID:178340", "title": "Corticotrophin and tetracosactrin depot-self-administered for the treatment of eczema.", "content": "The prolonged use of self-administered corticotrophin in the form of 'CMC ACTH' (Crookes) or 'Synacthen Depot' (Ciba) has been considered in twenty-seven patients with severe subactute of chronic eczema. Complications were not troublesome and the therapeutic response was good. Many of the patients were able to control their disease fully without the effort and discomfort of additional local treatment and patients' acceptance of the treatment was high.", "contents": "Corticotrophin and tetracosactrin depot-self-administered for the treatment of eczema. The prolonged use of self-administered corticotrophin in the form of 'CMC ACTH' (Crookes) or 'Synacthen Depot' (Ciba) has been considered in twenty-seven patients with severe subactute of chronic eczema. Complications were not troublesome and the therapeutic response was good. Many of the patients were able to control their disease fully without the effort and discomfort of additional local treatment and patients' acceptance of the treatment was high."} {"id": "PMID:178342", "title": "Relation between the inhibition of aggregation and the concentration of cAMP in human and rat platelets.", "content": "Adenosine inhibits the aggregation of human but not of rat platelets whereas both are inhibited by prostaglandin E1 or by the pyrimido-pyrimidine compound RA233. In human platelets all three agents increase adenosine-3'-5'-cyclic monophosphate (cAMP). If the inhibition of aggregation depended on this increase, adenosine might be expected not to increase cAMP in rat platelets. Under conditions in which adenosine inhibited aggregation and increased cAMP in human platelets, adenosine caused a similar increase in cAMP in rat platelets without inhibiting their aggregation. The aggregation of rat platelets was inhibited as effectively as that of human platelets by PGE1 or RA233 at concentrations which caused greater increases in cAMP than did the highest concentrations (2.8 X 10(-4) M) of adenosine it was possible to use. When the increase of cAMP in rat platelets by PGE1 was limited to that produced by adenosine, PGE1 like adenosine failed to inhibit aggregation. Therefore, the difference in the inhibitory effectiveness of adenosine on rat and human platelets was quantitative rather than qualitative and apparently depended on the inability of adenosine to increase cAMP sufficiently in rat platelets. When cAMP had been increased by adenosine, PGE1 or RA233, the addition of ADP caused cAMP to decrease rapidly in both human and rat platelets to between +22 and -18% of control values, except that the decrease in rat platelets was to +40% after RA233 had been present for 0.5 min before ADP. The increase in cAMP produced in rat platelets by adenosine at 5 X 10(-6) to 2.8 X 10(-4) M for 3 min was associated with a small increase in aggregation velocity. It is suggested that the comparative ineffectiveness of adenosine as an inhibitor of platelet aggregation, particularly with rat but less so also with human platelets, is because, unlike PGE1 or RA233, adenosine has two opposing actions on aggregation; one being inhibition by activating adenylate cyclase and increasing cAMP, and the other being potentiation by uptake. This hypothesis accounts for the present results as well as for the earlier observation that dipyridamole which prevents the uptake of adenosine potentiates its inhibitory effect on the aggregation of human platelets.", "contents": "Relation between the inhibition of aggregation and the concentration of cAMP in human and rat platelets. Adenosine inhibits the aggregation of human but not of rat platelets whereas both are inhibited by prostaglandin E1 or by the pyrimido-pyrimidine compound RA233. In human platelets all three agents increase adenosine-3'-5'-cyclic monophosphate (cAMP). If the inhibition of aggregation depended on this increase, adenosine might be expected not to increase cAMP in rat platelets. Under conditions in which adenosine inhibited aggregation and increased cAMP in human platelets, adenosine caused a similar increase in cAMP in rat platelets without inhibiting their aggregation. The aggregation of rat platelets was inhibited as effectively as that of human platelets by PGE1 or RA233 at concentrations which caused greater increases in cAMP than did the highest concentrations (2.8 X 10(-4) M) of adenosine it was possible to use. When the increase of cAMP in rat platelets by PGE1 was limited to that produced by adenosine, PGE1 like adenosine failed to inhibit aggregation. Therefore, the difference in the inhibitory effectiveness of adenosine on rat and human platelets was quantitative rather than qualitative and apparently depended on the inability of adenosine to increase cAMP sufficiently in rat platelets. When cAMP had been increased by adenosine, PGE1 or RA233, the addition of ADP caused cAMP to decrease rapidly in both human and rat platelets to between +22 and -18% of control values, except that the decrease in rat platelets was to +40% after RA233 had been present for 0.5 min before ADP. The increase in cAMP produced in rat platelets by adenosine at 5 X 10(-6) to 2.8 X 10(-4) M for 3 min was associated with a small increase in aggregation velocity. It is suggested that the comparative ineffectiveness of adenosine as an inhibitor of platelet aggregation, particularly with rat but less so also with human platelets, is because, unlike PGE1 or RA233, adenosine has two opposing actions on aggregation; one being inhibition by activating adenylate cyclase and increasing cAMP, and the other being potentiation by uptake. This hypothesis accounts for the present results as well as for the earlier observation that dipyridamole which prevents the uptake of adenosine potentiates its inhibitory effect on the aggregation of human platelets."} {"id": "PMID:178343", "title": "Surface sulphydryl groups and phagocytosis-associated oxidative metabolic changes in human polymorphonuclear leucocytes.", "content": "The role of surface sulphydryl (-SH) groups of human polymorphonuclear leucocytes on phagocytosis-associated oxidative metabolic changes was studied. p-Chloromercurybenzene sulphonic acid, a surface -SH group inhibitor, had no effect on phagocytosis, superoxide production during phagocytosis, or killing of S. aureus by the leucocytes, while it inhibited phagocytosis-associated stimulation of hexose monophosphate pathway activity and H2O2 production. In contrast, N-ethylmaleimide, which inhibits both intracellular and surface -SH groups, inhibited phagocytosis-associated oxidative metabolic changes. p-Chloromercurybenzene sulphonic acid also inhibited the stimulation of hexose monophosphate pathway activity by exogenous H2O2, suggesting a regulatory role of plasma membrane on the pathway's activity in human polymorphonuclear leucocytes. The results also suggest that: (I) superoxide production is the primary event of oxidative metabolic changes during phagocytosis, (2) superoxide plays an important role in the killing of S. aureus, and (3) the hexose monophosphate pathway plays a primary role in producing NADPH for H2O2 production from superoxide.", "contents": "Surface sulphydryl groups and phagocytosis-associated oxidative metabolic changes in human polymorphonuclear leucocytes. The role of surface sulphydryl (-SH) groups of human polymorphonuclear leucocytes on phagocytosis-associated oxidative metabolic changes was studied. p-Chloromercurybenzene sulphonic acid, a surface -SH group inhibitor, had no effect on phagocytosis, superoxide production during phagocytosis, or killing of S. aureus by the leucocytes, while it inhibited phagocytosis-associated stimulation of hexose monophosphate pathway activity and H2O2 production. In contrast, N-ethylmaleimide, which inhibits both intracellular and surface -SH groups, inhibited phagocytosis-associated oxidative metabolic changes. p-Chloromercurybenzene sulphonic acid also inhibited the stimulation of hexose monophosphate pathway activity by exogenous H2O2, suggesting a regulatory role of plasma membrane on the pathway's activity in human polymorphonuclear leucocytes. The results also suggest that: (I) superoxide production is the primary event of oxidative metabolic changes during phagocytosis, (2) superoxide plays an important role in the killing of S. aureus, and (3) the hexose monophosphate pathway plays a primary role in producing NADPH for H2O2 production from superoxide."} {"id": "PMID:178344", "title": "Surface sulphydryl groups and hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes.", "content": "The role of surface -SH groups on the hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes was studied. Endotoxin, taurocholic acid and concanvalin A stimulated [I-14C]glucose oxidation to a greater degree than [6-14C]glucose oxidation. The stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid and concanavalin A could be prevented by p-chloromercurybenzene sulphonic acid, an inhibitor of surface -SH groups. In contrast, polymorphonuclear leucocytes from four patients with chronic granulomatous disease failed to show stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid or concanavalin A.", "contents": "Surface sulphydryl groups and hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes. The role of surface -SH groups on the hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes was studied. Endotoxin, taurocholic acid and concanvalin A stimulated [I-14C]glucose oxidation to a greater degree than [6-14C]glucose oxidation. The stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid and concanavalin A could be prevented by p-chloromercurybenzene sulphonic acid, an inhibitor of surface -SH groups. In contrast, polymorphonuclear leucocytes from four patients with chronic granulomatous disease failed to show stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid or concanavalin A."} {"id": "PMID:178346", "title": "Adenocarcinoma of the uterine cervix a clinical and pathological appraisal.", "content": "Twenty-six cases of primary adenocarcinoma of the cervix are analyzed. Their clinical features are described and attention is drawn to the variable histological pattern of these tumors.", "contents": "Adenocarcinoma of the uterine cervix a clinical and pathological appraisal. Twenty-six cases of primary adenocarcinoma of the cervix are analyzed. Their clinical features are described and attention is drawn to the variable histological pattern of these tumors."} {"id": "PMID:178348", "title": "Biochemical and pathological changes in tissues of Friesian cattle during the experimental induction of copper deficiency.", "content": "1. Copper deficiency was induced in five Friesian cattle offered a semi-synthetic diet containing less than 1 mgCu/kg. Changes in blood and liver Cu contents and in the Cu-containing enzymes, ferroxidase I (caeruloplasmin; EC 1.16.3.1) and monoamine oxidase (EC 1.4.3.4) of plasma and cytochrome oxidase (EC 1.9.3.1) of liver and skeletal muscle were monitored during Cu depletion. 2. Rapid decreases in blood and liver Cu and plasma ferroxidase I activity were found at least 80 d before the first appearance of overt clinical signs of deficiency. Plasma monoamine oxidase and liver cytochrome oxidase activities decreased less rapidly and thus may provide useful indices of chronic Cu depletion.", "contents": "Biochemical and pathological changes in tissues of Friesian cattle during the experimental induction of copper deficiency. 1. Copper deficiency was induced in five Friesian cattle offered a semi-synthetic diet containing less than 1 mgCu/kg. Changes in blood and liver Cu contents and in the Cu-containing enzymes, ferroxidase I (caeruloplasmin; EC 1.16.3.1) and monoamine oxidase (EC 1.4.3.4) of plasma and cytochrome oxidase (EC 1.9.3.1) of liver and skeletal muscle were monitored during Cu depletion. 2. Rapid decreases in blood and liver Cu and plasma ferroxidase I activity were found at least 80 d before the first appearance of overt clinical signs of deficiency. Plasma monoamine oxidase and liver cytochrome oxidase activities decreased less rapidly and thus may provide useful indices of chronic Cu depletion."} {"id": "PMID:178349", "title": "Differential phosphorylation by GTP and ATP in isolated rod outer segments of the retina.", "content": "Isolated bovine rod outer segment protein is phosphorylated with GTP-gamma-32P and ATP-gamma 32P and to a much lesser extent by CTP-gamma-32P and UTP-gamma-32P. Phosphorylation with both GTP (GTP-kinase activity) and ATP (ATP-kinase activity) is markedly stimulated by light; phosphorylation with GTP is lower in dark-adapted and higher in light-adapted rod outer segments than is phosphorylation with ATP. Km values of 20 and 200 muM and Vmax values of 2.1 and 5.9 nmol/(mg min(-1)) were calculated using ATP and GTP, respectively, in light-adapted outer segments. When outer segments are incubated with GTP-gamma-32P under the usual conditions employed in these experiments, no formation of ATP-gamma-32P was detected by the techniques of high-pressure liquid chromatography and thin-layer chromatography. In intact, light-bleached outer segments, GTP appears to specifically phosphorylate rhodopsin. Histone and phosvitin are not phosphorylated to any appreciable extent by GTP. Histone appears to block rhodopsin phosphorylation by GTP while histone and, to some extent, phosvitin, both act as substrates for ATP-kinase activity. Cyclic AMP and other adenine derivates have a marked inhibitory effect on GTP-kinase activity. Phosphate also inhibits GTP-kinase activity but stimulates ATP-kinase activity. Such differences in phosphorylation with GTP and ATP indicate that these activities are either due to separate enzyme systems or, if only one enzyme is involved, the activities are under separate physiological control in the photoreceptor unit.", "contents": "Differential phosphorylation by GTP and ATP in isolated rod outer segments of the retina. Isolated bovine rod outer segment protein is phosphorylated with GTP-gamma-32P and ATP-gamma 32P and to a much lesser extent by CTP-gamma-32P and UTP-gamma-32P. Phosphorylation with both GTP (GTP-kinase activity) and ATP (ATP-kinase activity) is markedly stimulated by light; phosphorylation with GTP is lower in dark-adapted and higher in light-adapted rod outer segments than is phosphorylation with ATP. Km values of 20 and 200 muM and Vmax values of 2.1 and 5.9 nmol/(mg min(-1)) were calculated using ATP and GTP, respectively, in light-adapted outer segments. When outer segments are incubated with GTP-gamma-32P under the usual conditions employed in these experiments, no formation of ATP-gamma-32P was detected by the techniques of high-pressure liquid chromatography and thin-layer chromatography. In intact, light-bleached outer segments, GTP appears to specifically phosphorylate rhodopsin. Histone and phosvitin are not phosphorylated to any appreciable extent by GTP. Histone appears to block rhodopsin phosphorylation by GTP while histone and, to some extent, phosvitin, both act as substrates for ATP-kinase activity. Cyclic AMP and other adenine derivates have a marked inhibitory effect on GTP-kinase activity. Phosphate also inhibits GTP-kinase activity but stimulates ATP-kinase activity. Such differences in phosphorylation with GTP and ATP indicate that these activities are either due to separate enzyme systems or, if only one enzyme is involved, the activities are under separate physiological control in the photoreceptor unit."} {"id": "PMID:178350", "title": "Effects of paramagnetic shift reagents on the 13C nuclear magnetic resonance spectra of egg phosphatidylcholine enriched with 13C in the N-methyl carbons.", "content": "Effects of paramagnetic shift reagents on the 13C NMR spectra obtained from single-walled vesicle dispersions of egg phosphatidylcholine enriched with 13C in the N-methyl carbons are investigated. Spectra obtained at 25.1 MHz show that, at Yb3+ to phospholipid molar ratios as low as 0.06, complete resolution of the N-methyl carbon resonances is obtained from molecules on the inner and outer faces of the vesicle bilayer. No precipitation of the vesicles is caused by Yb3+ at these concentrations nor is appreciable line broadening observed. Other paramagnetic shift reagents frequently used in proton NMR investigations of phosphatidylcholine vesicles do not give complete separation of the N-methyl 13C signals from the two bilayer surfaces. K3Fe(CN)b,Eu3+, and Pr3+ cause precipitation of the phosphatidylcholine vesicles at concentrations, which give only incomplete resolution of these signals. T1 measurements of the resonances separated by Yb3+ indicate that the choline groups on the inner bilayer surface are less mobile than are the same groups in the outer surface. Gated proton decoupling measurements, which show that the nuclear Overhauser effect is 2.8 +/- 0.1, indicate that the dominant mode of relaxation is dipolar interaction.", "contents": "Effects of paramagnetic shift reagents on the 13C nuclear magnetic resonance spectra of egg phosphatidylcholine enriched with 13C in the N-methyl carbons. Effects of paramagnetic shift reagents on the 13C NMR spectra obtained from single-walled vesicle dispersions of egg phosphatidylcholine enriched with 13C in the N-methyl carbons are investigated. Spectra obtained at 25.1 MHz show that, at Yb3+ to phospholipid molar ratios as low as 0.06, complete resolution of the N-methyl carbon resonances is obtained from molecules on the inner and outer faces of the vesicle bilayer. No precipitation of the vesicles is caused by Yb3+ at these concentrations nor is appreciable line broadening observed. Other paramagnetic shift reagents frequently used in proton NMR investigations of phosphatidylcholine vesicles do not give complete separation of the N-methyl 13C signals from the two bilayer surfaces. K3Fe(CN)b,Eu3+, and Pr3+ cause precipitation of the phosphatidylcholine vesicles at concentrations, which give only incomplete resolution of these signals. T1 measurements of the resonances separated by Yb3+ indicate that the choline groups on the inner bilayer surface are less mobile than are the same groups in the outer surface. Gated proton decoupling measurements, which show that the nuclear Overhauser effect is 2.8 +/- 0.1, indicate that the dominant mode of relaxation is dipolar interaction."} {"id": "PMID:178351", "title": "Hormonal regulation of pancreatic islet adenyl cyclase.", "content": "Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.", "contents": "Hormonal regulation of pancreatic islet adenyl cyclase. Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process."} {"id": "PMID:178352", "title": "Determination of molar ratios of vesicular stomatitis virus induced RNA species in BHK21 cells.", "content": "A modified procedure for analysis of RNA in denaturing formamide-polyacrylamide slab gels containing 6 M urea is described. Using this technique, in conjucntion with fluorographic analysis, we determined molecular weights and molar ratios of the various vesicular stomatitis virus (VSV) induced RNAs in BHK21 cells. A comparison of the molar ratios of virus-specific mRHAs and their putative protein products in these cells suggests that there is little, if any, translational control of viral gene expression during acute VSV infection.", "contents": "Determination of molar ratios of vesicular stomatitis virus induced RNA species in BHK21 cells. A modified procedure for analysis of RNA in denaturing formamide-polyacrylamide slab gels containing 6 M urea is described. Using this technique, in conjucntion with fluorographic analysis, we determined molecular weights and molar ratios of the various vesicular stomatitis virus (VSV) induced RNAs in BHK21 cells. A comparison of the molar ratios of virus-specific mRHAs and their putative protein products in these cells suggests that there is little, if any, translational control of viral gene expression during acute VSV infection."} {"id": "PMID:178353", "title": "Synthesis and properties of diastereoisomers of adenosine 5'-(O-1-thiotriphosphate) and adenosine 5'-(O-2-thiotriphosphate).", "content": "The chemical synthesis of adenosine 5'-(O-1-thiotriphosphate) (ATPalphaS) and adenosine 5'-(O-2-thiotriphosphate) (ATPbetaS) is described. Both exist as a pair of diastereomers, A and B. The isomers of ATPalphaS can be distinguished on the basis of their different reaction rates with myokinase as well as nucleoside diphosphate kinase. With both enzymes, isomer A reacts fast whereas isomer B reacts considerably more slowly. Phosphorylation of a mixture of isomers of ADPalphaS with pyruvate or acetate kinase yields ATPalphaS, isomer A, whereas the phosphoryl transfer with creatine or arginine kinase yields isomer B. The isomers of ATPbetaS differ in their reactivity with myosin. Isomer A is readily hydrolyzed, whereas isomer B is not. However, isomer B reacts faster with nucleoside diphosphate kinase and ADP than isomer A. Phosphoryl transfer with pyruvate kinase onto ADPbetaS yields ATPbetaS, isomer A, with acetate kinase, isomer B.", "contents": "Synthesis and properties of diastereoisomers of adenosine 5'-(O-1-thiotriphosphate) and adenosine 5'-(O-2-thiotriphosphate). The chemical synthesis of adenosine 5'-(O-1-thiotriphosphate) (ATPalphaS) and adenosine 5'-(O-2-thiotriphosphate) (ATPbetaS) is described. Both exist as a pair of diastereomers, A and B. The isomers of ATPalphaS can be distinguished on the basis of their different reaction rates with myokinase as well as nucleoside diphosphate kinase. With both enzymes, isomer A reacts fast whereas isomer B reacts considerably more slowly. Phosphorylation of a mixture of isomers of ADPalphaS with pyruvate or acetate kinase yields ATPalphaS, isomer A, whereas the phosphoryl transfer with creatine or arginine kinase yields isomer B. The isomers of ATPbetaS differ in their reactivity with myosin. Isomer A is readily hydrolyzed, whereas isomer B is not. However, isomer B reacts faster with nucleoside diphosphate kinase and ADP than isomer A. Phosphoryl transfer with pyruvate kinase onto ADPbetaS yields ATPbetaS, isomer A, with acetate kinase, isomer B."} {"id": "PMID:178354", "title": "Partial purification and characterization of adenosine- and guanosine-3',5'-monophosphate phosphodiesterases from human lung tissue.", "content": "Crude extracts of human lung tissue were examined for cyclic adenosine- and guanosine-3',5'-monophosphate (cAMP and cGMP) phosphodiesterase activities. Nonlinear reciprocal plots were observed for each substrate. DEAE-Sephadex chromatography of the extracts revealed four main fractions of activity, which were further purified by Sephadex gel filtration. The phosphodiesterase activity of the resulting individual fractions was partially characterized with respect to substrate specificity, kinetic parameters, apparent molecular weight (gel filtration), thermal stability at 30 and 37 degrees C, effect of the cyclic nucleotide not utilized as substrate, and the possible influence of Ca2+-dependent protein activator. The results indicate that the tissue contains phosphodiesterases with strict specificity and a high apparent affinity for each of the two cyclic nucleotides (the Km values determined were approximately 0.3-0.4 muM). The high affinity cAMP phosphodiesterase activity was enriched in two of the purified fractions; both activities probably represent fragments of the native high affinity cAMP specific enzyme. A third purified phosphodiesterase showed mixed substrate specificity. The Km value recorded for hydrolysis of either substrate with this enzyme was approximately 25 muM. A fourth, irregularly occurring, phosphodiesterase activity also showed mixed substrate specificity. The Km value registered for hydrolysis of either substrate with this fraction was approximately 0.4 muM. There was no evidence for a Ca2+-dependent specific activation by a boiled lung tissue supernatant of any of the purified enzymes.", "contents": "Partial purification and characterization of adenosine- and guanosine-3',5'-monophosphate phosphodiesterases from human lung tissue. Crude extracts of human lung tissue were examined for cyclic adenosine- and guanosine-3',5'-monophosphate (cAMP and cGMP) phosphodiesterase activities. Nonlinear reciprocal plots were observed for each substrate. DEAE-Sephadex chromatography of the extracts revealed four main fractions of activity, which were further purified by Sephadex gel filtration. The phosphodiesterase activity of the resulting individual fractions was partially characterized with respect to substrate specificity, kinetic parameters, apparent molecular weight (gel filtration), thermal stability at 30 and 37 degrees C, effect of the cyclic nucleotide not utilized as substrate, and the possible influence of Ca2+-dependent protein activator. The results indicate that the tissue contains phosphodiesterases with strict specificity and a high apparent affinity for each of the two cyclic nucleotides (the Km values determined were approximately 0.3-0.4 muM). The high affinity cAMP phosphodiesterase activity was enriched in two of the purified fractions; both activities probably represent fragments of the native high affinity cAMP specific enzyme. A third purified phosphodiesterase showed mixed substrate specificity. The Km value recorded for hydrolysis of either substrate with this enzyme was approximately 25 muM. A fourth, irregularly occurring, phosphodiesterase activity also showed mixed substrate specificity. The Km value registered for hydrolysis of either substrate with this fraction was approximately 0.4 muM. There was no evidence for a Ca2+-dependent specific activation by a boiled lung tissue supernatant of any of the purified enzymes."} {"id": "PMID:178355", "title": "Specific modification of an effector binding site of phosphofructokinase by pyridoxal phasphate.", "content": "Conditions are described for the covalent modification of rabbit skeletal muscle phosphofructokinase by pyridoxal phosphate plus sodium borohydride to produce an enzyme that appears by a number of criteria to be modified at the citrate binding site. Evidence that modification occurs at this site is as follows. (1) Protection against activity loss due to modification is provided by the combination of MgATP and citrate, whereas neither low concentrations of citrate nor MgATP alone is effective. This is consistent with the increased affinity for citrate that is observed in the presence of MgATP. (2) The extensive changes in activity and equilibrium binding result from the incorporation of only 1 mol of pyridoxal phosphate per mol of protomer. (3) Modification greatly increases sensitivity to MgATP inhibition, an effect consistent with the known synergism between MgATP and citrate. (4) The affinity of the enzyme for both MgATP and MgIPT at the catalytic site is increased by the modification. (5) The sensitivity of the enzyme to citrate inhibition is greatly diminished following covalent modification. (6) Modification abolishes the equilibrium binding of citrate. (7) Enhanced binding of MgATP is observed following modification, a result consistent with the enhancement of MgATP binding by citrate. Phosphofructokinase protected by citrate plus MgATP can also be modified by the incorporation of 1 or more mol of pyridoxal phosphate, but the enzyme so produced is capable of interacting with citrate and shows none of the properties herein described for the enzyme modified in the absence of citrate.", "contents": "Specific modification of an effector binding site of phosphofructokinase by pyridoxal phasphate. Conditions are described for the covalent modification of rabbit skeletal muscle phosphofructokinase by pyridoxal phosphate plus sodium borohydride to produce an enzyme that appears by a number of criteria to be modified at the citrate binding site. Evidence that modification occurs at this site is as follows. (1) Protection against activity loss due to modification is provided by the combination of MgATP and citrate, whereas neither low concentrations of citrate nor MgATP alone is effective. This is consistent with the increased affinity for citrate that is observed in the presence of MgATP. (2) The extensive changes in activity and equilibrium binding result from the incorporation of only 1 mol of pyridoxal phosphate per mol of protomer. (3) Modification greatly increases sensitivity to MgATP inhibition, an effect consistent with the known synergism between MgATP and citrate. (4) The affinity of the enzyme for both MgATP and MgIPT at the catalytic site is increased by the modification. (5) The sensitivity of the enzyme to citrate inhibition is greatly diminished following covalent modification. (6) Modification abolishes the equilibrium binding of citrate. (7) Enhanced binding of MgATP is observed following modification, a result consistent with the enhancement of MgATP binding by citrate. Phosphofructokinase protected by citrate plus MgATP can also be modified by the incorporation of 1 or more mol of pyridoxal phosphate, but the enzyme so produced is capable of interacting with citrate and shows none of the properties herein described for the enzyme modified in the absence of citrate."} {"id": "PMID:178356", "title": "Stimulation of ascites tumor RNA polymerase II by protein kinase.", "content": "The activity of purified RNA polymerase II from Novikoff ascites tumor cells is stimulated 5-7-fold by a purified protein factor. This protein factor, designated HLF2, has extensive protein kinase activity and catalyzed the incorporation of gamma-32G from ATP into protein under normal RNA polymerase assay conditions. Protein phosphorylation is totally dependent on the presence of HLF2 and is stimulated 2-3-fold by the presence of highly purified RNA polymerase II. The purification procedure developed for the isolation of the polymerase stimulatory factor resulted in a 4000-fold purification of a protein kinase. Chromatography on carboxymethylcellulose, phosphocellulose, and Sephadex G-100 did not resolve polymerase stimulatory activity from protein kinase activity. Adenylimidodiphosphate (AMP-PNP), an inhibitor of protein kinases, inhibited the stimulatory activity of purified factor by 80%. The heat denaturation profile of protein kinase was paralleled by the loss of polymerase stimulatory activity. Concentrations of (NH4)2SO4 which are known to inhibit polymerase stimulation (Lee and Dahmus, 1973) also inhibit protein kinase activity. The protein kinase activity associated with stimulatory factor catalyzes the phosphorylation of basic proteins such as protamine or histone. The protein kinase is not stimulated by cyclic 3', 5'-AMP or -GMP over a concentration range of 10(-6)-10(-4)M. Furthermore, protein kinase activity is not inhibited by either the regulatory subunit of rabbit muscle protein kinase or by the heat-stable inhibitor of cyclic 3', 5'-AMP-dependent protein kinases. Protein kinase activity is stimulated by KCl or NH4Cl and is inhibited by MnCl2. The apparent Km values, determined in the presence of 4 mM Mg2+, are 0.02 mM for ATP, and 4.1 mM for GTP.", "contents": "Stimulation of ascites tumor RNA polymerase II by protein kinase. The activity of purified RNA polymerase II from Novikoff ascites tumor cells is stimulated 5-7-fold by a purified protein factor. This protein factor, designated HLF2, has extensive protein kinase activity and catalyzed the incorporation of gamma-32G from ATP into protein under normal RNA polymerase assay conditions. Protein phosphorylation is totally dependent on the presence of HLF2 and is stimulated 2-3-fold by the presence of highly purified RNA polymerase II. The purification procedure developed for the isolation of the polymerase stimulatory factor resulted in a 4000-fold purification of a protein kinase. Chromatography on carboxymethylcellulose, phosphocellulose, and Sephadex G-100 did not resolve polymerase stimulatory activity from protein kinase activity. Adenylimidodiphosphate (AMP-PNP), an inhibitor of protein kinases, inhibited the stimulatory activity of purified factor by 80%. The heat denaturation profile of protein kinase was paralleled by the loss of polymerase stimulatory activity. Concentrations of (NH4)2SO4 which are known to inhibit polymerase stimulation (Lee and Dahmus, 1973) also inhibit protein kinase activity. The protein kinase activity associated with stimulatory factor catalyzes the phosphorylation of basic proteins such as protamine or histone. The protein kinase is not stimulated by cyclic 3', 5'-AMP or -GMP over a concentration range of 10(-6)-10(-4)M. Furthermore, protein kinase activity is not inhibited by either the regulatory subunit of rabbit muscle protein kinase or by the heat-stable inhibitor of cyclic 3', 5'-AMP-dependent protein kinases. Protein kinase activity is stimulated by KCl or NH4Cl and is inhibited by MnCl2. The apparent Km values, determined in the presence of 4 mM Mg2+, are 0.02 mM for ATP, and 4.1 mM for GTP."} {"id": "PMID:178357", "title": "Phosphorylation of double-stranded DNAs by T4 polynucleotide kinase.", "content": "The phosphorylation by T4 polynucleotide kinase of various double-stranded DNAs containing defined 5'-hydroxyl end group structures has been studied. Particular emphasis was placed on finding conditions that allow complete phosphorylation. The DNAs employed were homodeoxyoligonucleotides annealed on the corresponding homopolymers, DNA duplexes corresponding to parts of the genes for alanine yeast tRNA, and a suppressor tyrosine tRNA from Escherichia coli. The rate of phosphoylation of DNAs with 5'-hydroxyl groups in gaps was approximately ten times slower than for the corresponding single-stranded DNA. At low concentrations of ATP, 1 muM, incomplete phosphorylation was obtained, whereas with higher concentrations of ATP, 30 muM, complete phosphorylation was achieved. In the case of DNAs with 5'-hydroxyl groups at nicks approximately 30% phosphorylation could be detected using 30 muM ATP. A DNA containing protruding 5'-hydroxyl group ends was phosphorylated to completion using the same conditions as for single-stranded DNA, i.e., a ratio between the concentrations of ATP and 5'-hydroxyl groups of 5:1 and a concentration of ATP of approximately 1 muM. For a number of DNAs containing protruding 3'-hydroxyl group ends and one DNA containing even ends incomplete phosphorylation was found under similar conditions. For all these DNAs a plateau level was observed varying from 20 to 45% of complete phosphorylation. At 20 muM and higher ATP concentrations, the phosphorylation was complete also for these DNAs. With low concentrations of ATP a rapid production of inorganic phosphate was noted for all the latter DNAs. The apparent equilibrium constants for the forward and reverse reaction were determined for a number of different DNAs, and these data revealed that the plateau levels of phosphorylation obtained at low concentrations of ATP for DNAs with protruding 3'-hydroxyl group and even ends is not a true equilibrium resulting from the forward and reverse reaction. It is suggested that the plateau levels are due to formation of inactive enzyme-substrate and enzyme-product complexes. For all double-stranded DNAs tested, except DNAs containing protruding 5'-hydroxyl group ends, addition of KCl to the reaction mixture resulted in a drastic decrease in the rate of phosphorylation, as well as in the maximum level phosphorylated. Spermine, on the other hand, had little influence. Both of these agents have previously been shown to activate T4 polynucleotide kinase using single-stranded DNAs as substrates (Lillehaug, J.R., and Kleppe, K. (1975), Biochemistry 14, 1221). The inhibition of phosphorylation of double-stranded DNAs by salt might be the result of stabilization of the 5'-hydroxyl group regions of these DNAs.", "contents": "Phosphorylation of double-stranded DNAs by T4 polynucleotide kinase. The phosphorylation by T4 polynucleotide kinase of various double-stranded DNAs containing defined 5'-hydroxyl end group structures has been studied. Particular emphasis was placed on finding conditions that allow complete phosphorylation. The DNAs employed were homodeoxyoligonucleotides annealed on the corresponding homopolymers, DNA duplexes corresponding to parts of the genes for alanine yeast tRNA, and a suppressor tyrosine tRNA from Escherichia coli. The rate of phosphoylation of DNAs with 5'-hydroxyl groups in gaps was approximately ten times slower than for the corresponding single-stranded DNA. At low concentrations of ATP, 1 muM, incomplete phosphorylation was obtained, whereas with higher concentrations of ATP, 30 muM, complete phosphorylation was achieved. In the case of DNAs with 5'-hydroxyl groups at nicks approximately 30% phosphorylation could be detected using 30 muM ATP. A DNA containing protruding 5'-hydroxyl group ends was phosphorylated to completion using the same conditions as for single-stranded DNA, i.e., a ratio between the concentrations of ATP and 5'-hydroxyl groups of 5:1 and a concentration of ATP of approximately 1 muM. For a number of DNAs containing protruding 3'-hydroxyl group ends and one DNA containing even ends incomplete phosphorylation was found under similar conditions. For all these DNAs a plateau level was observed varying from 20 to 45% of complete phosphorylation. At 20 muM and higher ATP concentrations, the phosphorylation was complete also for these DNAs. With low concentrations of ATP a rapid production of inorganic phosphate was noted for all the latter DNAs. The apparent equilibrium constants for the forward and reverse reaction were determined for a number of different DNAs, and these data revealed that the plateau levels of phosphorylation obtained at low concentrations of ATP for DNAs with protruding 3'-hydroxyl group and even ends is not a true equilibrium resulting from the forward and reverse reaction. It is suggested that the plateau levels are due to formation of inactive enzyme-substrate and enzyme-product complexes. For all double-stranded DNAs tested, except DNAs containing protruding 5'-hydroxyl group ends, addition of KCl to the reaction mixture resulted in a drastic decrease in the rate of phosphorylation, as well as in the maximum level phosphorylated. Spermine, on the other hand, had little influence. Both of these agents have previously been shown to activate T4 polynucleotide kinase using single-stranded DNAs as substrates (Lillehaug, J.R., and Kleppe, K. (1975), Biochemistry 14, 1221). The inhibition of phosphorylation of double-stranded DNAs by salt might be the result of stabilization of the 5'-hydroxyl group regions of these DNAs."} {"id": "PMID:178358", "title": "Estrogen binding proteins of calf uterus. Inhibition of aggregation and dissociation of receptor by chemical perturbation with NaSCN.", "content": "Sodium thiocyanate up to 0.5 M is compatible with a stable estradiol-t-receptor complex during sucrose gradient centrifugation; however, the maximum permissible concentration in 0.1 M during Sephadex G-100 and G-200 chromatography. When NaSCN 0.1 M is added to low-salt cytosol (approximately 7 mg of protein/ml); (1) age-dependent aggregation of receptor is inhibited; (2) peaks of estrogen-binding activity in sucrose gradients and on Sephadex chromatography are sharp; (3) instead of the usual larger molecular states (\"8S\") found in low salt, most of estrogen receptor is under the following form: 4.1S; Stokes radius, 36 A; mol wt 61 000; flfo, 1.25; homogeneous at electrofocusing, with isoelectric point at 6.0. When cytosol containing NaSCN 0.1 M is diluted down to 2-3 mg of protein/ml or, only for sucrose gradients, NaSCN concentration is increased to 0.4-0.5 M, the 61000 dalton species decreases, being substituted, without loss of bound estradiol-t, by the following estrogen-binding entity: 28S; Stokes radius, 28 A; mol wt 32 000; flfo, 1.44. In the presence of NaSCN, KCl up to 0.4 M does not affect in a significant manner the molecular properties of the above forms. When NaSCN is dialyzed out, most receptor reverts to a 8-9S state. When cytosol is preincubated with Ca2+ (4 mM) and KCl (0.4 M) before addition of NaSCN, the above picture is modified only in the following aspects: (1) Sephadex chromatography peaks are broader and slightly but reproducibly shifted toward higher elution volumes; (2) the electrofocusing pattern consists of a two-peak heterogeneous band shifted toward higher pH (isoelectric points 6.4 and 6.6); (3) upon dialysis of NaSCN there is little or no reversion to faster sedimenting states. These modifications appear to depend on limited proteolytic attack of receptor by Ca2+ -activated receptor transforming factor (RTF), not on binding of Ca2+ to receptor. Present data suggest that the 4.1S entity is a dimer resulting from side-by-side pairing of 2.8S subunits. Molecular dimension of larger receptor forms purified from cytosol are consistent with the hypothesis that under native conditions in vivo dimers are coupled end-by-end into tetrameric structures with two stronger (between subunits) and two weaker (between dimers) bonding regions, and that tetramers may further self-associate. While NaSCN reversibly releases native dimers and subunits by direct impairment of intersubunit bonds, Ca2+ activated RTF irreversibly and specifically releases slightly modified, about 60000 mol wt dimers, by preferential proteolytic attack of the weaker bonding regions and indirect destruction of involved bonds. In vivo, this effect of RTF may be instrumental in mobilization and nuclear penetration of receptor-estradiol complex. Heteroassociation of receptor with other proteins of cytosol is not excluded by the above hypothesis.", "contents": "Estrogen binding proteins of calf uterus. Inhibition of aggregation and dissociation of receptor by chemical perturbation with NaSCN. Sodium thiocyanate up to 0.5 M is compatible with a stable estradiol-t-receptor complex during sucrose gradient centrifugation; however, the maximum permissible concentration in 0.1 M during Sephadex G-100 and G-200 chromatography. When NaSCN 0.1 M is added to low-salt cytosol (approximately 7 mg of protein/ml); (1) age-dependent aggregation of receptor is inhibited; (2) peaks of estrogen-binding activity in sucrose gradients and on Sephadex chromatography are sharp; (3) instead of the usual larger molecular states (\"8S\") found in low salt, most of estrogen receptor is under the following form: 4.1S; Stokes radius, 36 A; mol wt 61 000; flfo, 1.25; homogeneous at electrofocusing, with isoelectric point at 6.0. When cytosol containing NaSCN 0.1 M is diluted down to 2-3 mg of protein/ml or, only for sucrose gradients, NaSCN concentration is increased to 0.4-0.5 M, the 61000 dalton species decreases, being substituted, without loss of bound estradiol-t, by the following estrogen-binding entity: 28S; Stokes radius, 28 A; mol wt 32 000; flfo, 1.44. In the presence of NaSCN, KCl up to 0.4 M does not affect in a significant manner the molecular properties of the above forms. When NaSCN is dialyzed out, most receptor reverts to a 8-9S state. When cytosol is preincubated with Ca2+ (4 mM) and KCl (0.4 M) before addition of NaSCN, the above picture is modified only in the following aspects: (1) Sephadex chromatography peaks are broader and slightly but reproducibly shifted toward higher elution volumes; (2) the electrofocusing pattern consists of a two-peak heterogeneous band shifted toward higher pH (isoelectric points 6.4 and 6.6); (3) upon dialysis of NaSCN there is little or no reversion to faster sedimenting states. These modifications appear to depend on limited proteolytic attack of receptor by Ca2+ -activated receptor transforming factor (RTF), not on binding of Ca2+ to receptor. Present data suggest that the 4.1S entity is a dimer resulting from side-by-side pairing of 2.8S subunits. Molecular dimension of larger receptor forms purified from cytosol are consistent with the hypothesis that under native conditions in vivo dimers are coupled end-by-end into tetrameric structures with two stronger (between subunits) and two weaker (between dimers) bonding regions, and that tetramers may further self-associate. While NaSCN reversibly releases native dimers and subunits by direct impairment of intersubunit bonds, Ca2+ activated RTF irreversibly and specifically releases slightly modified, about 60000 mol wt dimers, by preferential proteolytic attack of the weaker bonding regions and indirect destruction of involved bonds. In vivo, this effect of RTF may be instrumental in mobilization and nuclear penetration of receptor-estradiol complex. Heteroassociation of receptor with other proteins of cytosol is not excluded by the above hypothesis."} {"id": "PMID:178359", "title": "Characterization of the plasma lipoproteins and apoproteins of the Erythrocebus patas monkey.", "content": "Patas monkey lipoproteins were fractionated into four distinct classes by a combination of ultracentrifugation and Geon-Pevikon block electrophoresis and characterized with respect to their chemical and physical properties. Very low density lipoproteins (VLDL) were isolated at d is less than 1.006, were triglyceride rich, and were in the size range 300-850 A. They were similar in apoprotein content to the VLDL of man, dog, and swine. The Patas monkey low density lipoprotein referred to as LDL-I had beta mobility and a size which ranged from 190 to 240 A in diameter. Their chemical composition and apoprotein content were similar to those of human LDL. A second low density lipoprotein referred to as LDL-II occurred at a density of 1.05-1.085, ranged in size from 190 to 300 A, and contained the B, arginine-rich, and A-I apoproteins. Differences between LDL-I and LDL-II included a higher sialic acid content for LDL-II and lipid to protein ratios of 3.7 and 3.0 for LDL-I and LDL-II, respectively. In addition, the LDL-II, but not LDL-I, reacted immunochemically with antisera prepared to human Lp(a). The physical, chemical, and immunochemical properties indicated that monkey LDL-II were equivalent to the human Lp(a). Patas monkey HDL, equivalent to human HDL, were protein and phospholipid rich and ranged in size from 70 to 100 A in diameter. The two major HDL apoproteins, A-I and A-II, were isolated from apo-HDL by column chromatography. The amino-terminal sequence of Patas A-I showed striking homology to that reported for human, dog, and swing A-I. The amino acid composition of monkey A-II was very similar to that of human A-II; however, unlike human A-II, the monkey apoprotein was shown to exist as a monomer similar to that reported for Rhesus monkey A-II. The similarities between the plasma lipoproteins of the monkey and of man suggest that the Patas monkey would serve as a suitable model for metabolic studies.", "contents": "Characterization of the plasma lipoproteins and apoproteins of the Erythrocebus patas monkey. Patas monkey lipoproteins were fractionated into four distinct classes by a combination of ultracentrifugation and Geon-Pevikon block electrophoresis and characterized with respect to their chemical and physical properties. Very low density lipoproteins (VLDL) were isolated at d is less than 1.006, were triglyceride rich, and were in the size range 300-850 A. They were similar in apoprotein content to the VLDL of man, dog, and swine. The Patas monkey low density lipoprotein referred to as LDL-I had beta mobility and a size which ranged from 190 to 240 A in diameter. Their chemical composition and apoprotein content were similar to those of human LDL. A second low density lipoprotein referred to as LDL-II occurred at a density of 1.05-1.085, ranged in size from 190 to 300 A, and contained the B, arginine-rich, and A-I apoproteins. Differences between LDL-I and LDL-II included a higher sialic acid content for LDL-II and lipid to protein ratios of 3.7 and 3.0 for LDL-I and LDL-II, respectively. In addition, the LDL-II, but not LDL-I, reacted immunochemically with antisera prepared to human Lp(a). The physical, chemical, and immunochemical properties indicated that monkey LDL-II were equivalent to the human Lp(a). Patas monkey HDL, equivalent to human HDL, were protein and phospholipid rich and ranged in size from 70 to 100 A in diameter. The two major HDL apoproteins, A-I and A-II, were isolated from apo-HDL by column chromatography. The amino-terminal sequence of Patas A-I showed striking homology to that reported for human, dog, and swing A-I. The amino acid composition of monkey A-II was very similar to that of human A-II; however, unlike human A-II, the monkey apoprotein was shown to exist as a monomer similar to that reported for Rhesus monkey A-II. The similarities between the plasma lipoproteins of the monkey and of man suggest that the Patas monkey would serve as a suitable model for metabolic studies."} {"id": "PMID:178360", "title": "Isolation and characterization of a dog serum lipoprotein having apolipoprotein A-I as its predominant protein constituent.", "content": "The serum high density lipoproteins (HDL) of normolipemic dogs (beagles) were isolated in the density range of p 1.063 to 1.21 g/ml, and characterized in terms of composition and physical properties (flotation and diffusion coefficients, partial specific volume, molecular weight, electrophoretic mobility, ultraviolet absorption, and circular dichroism). The results indicated that canine HDL is a relatively homogeneous class with a molecular weight of about 230 000 and general properties similar to those reported for human HDL. After delipidation, the resulting apolipoprotein, apo-HDL, was fractionated by Sephadex G-200 column chromatography in urea or guanidine hydrochloride solutions. About 90% of the apo-HDL consisted of a protein with a molecular weight of about 28 000, similar in amino acid composition to human apolipoprotein A-I and having the same NH2 terminus (aspartic acid) and COOH terminus (glutamine) and no carbohydrates. Two other proteins were isolated, one having an apparent mol wt of 55 000 and representing, at least in part, an aggregate of apolipoprotein A-I and the other component with a mol wt of 8000, not yet characterized. The results indicate that canine HDL, as an intact complex, has general physical properties that lie between those reported for human HDL2 and HDL3, and that it differs compositionally from the human products mainly in its predominant content of apo-A-I. These findings together with evidence for the relatively homogeneous nature of the canine HDL provide new prospects for unraveling the relationship between polypeptide composition and HDL structure.", "contents": "Isolation and characterization of a dog serum lipoprotein having apolipoprotein A-I as its predominant protein constituent. The serum high density lipoproteins (HDL) of normolipemic dogs (beagles) were isolated in the density range of p 1.063 to 1.21 g/ml, and characterized in terms of composition and physical properties (flotation and diffusion coefficients, partial specific volume, molecular weight, electrophoretic mobility, ultraviolet absorption, and circular dichroism). The results indicated that canine HDL is a relatively homogeneous class with a molecular weight of about 230 000 and general properties similar to those reported for human HDL. After delipidation, the resulting apolipoprotein, apo-HDL, was fractionated by Sephadex G-200 column chromatography in urea or guanidine hydrochloride solutions. About 90% of the apo-HDL consisted of a protein with a molecular weight of about 28 000, similar in amino acid composition to human apolipoprotein A-I and having the same NH2 terminus (aspartic acid) and COOH terminus (glutamine) and no carbohydrates. Two other proteins were isolated, one having an apparent mol wt of 55 000 and representing, at least in part, an aggregate of apolipoprotein A-I and the other component with a mol wt of 8000, not yet characterized. The results indicate that canine HDL, as an intact complex, has general physical properties that lie between those reported for human HDL2 and HDL3, and that it differs compositionally from the human products mainly in its predominant content of apo-A-I. These findings together with evidence for the relatively homogeneous nature of the canine HDL provide new prospects for unraveling the relationship between polypeptide composition and HDL structure."} {"id": "PMID:178361", "title": "Study of the transverse diffusion of spin labeled phospholipids in biological membranes. I. Human red bloods cells.", "content": "Spin labeled analogs of phosphatidylcholine were used to study the transverse diffusion (flip-flop) of phospholipids in the erythrocyte membrane. The nitroxide spin label was placed either on the beta acyl chain or on the choline group. These labeled phosphatidylcholine molecules were incorporated into the membrane by incubation of the red cells at 22 degrees C with sonicated spin-labed phosphatidylcholine vesicles from which all traces of free fatty acids and lyso derivatives were carefully removed by bovine serum albumin treatment. This incorporation did not provide any change in the morphology of the cell as indicated by scanning electron microscopy. When spin-labeled phosphatidylcholine, having a nitroxide on the beta chain but near the polar head-group, was incorporated into the erythrocyte membrane, ascorbate treatment at 0 degrees C allows selective reduction of the signal coming from the outer layer of the membrane. When the label was on the polar head-group, the inner content of the erythrocyte rapidly reduced the label facing the cytoplasm, thus creaging a spontaneous anisotropy of the labeling. The anisotropic distribution of spin-labeled phosphatidylcholine in the erythrocyte membrane was found to be stable at 22 and 37 degrees C for more than 4 h. It is therefore concluded that the rate of outside-inside and inside-outside transition is so slow that the anisotropic distribution of the phospholipids in the erythrocyte membrane can be maintained during cell life.", "contents": "Study of the transverse diffusion of spin labeled phospholipids in biological membranes. I. Human red bloods cells. Spin labeled analogs of phosphatidylcholine were used to study the transverse diffusion (flip-flop) of phospholipids in the erythrocyte membrane. The nitroxide spin label was placed either on the beta acyl chain or on the choline group. These labeled phosphatidylcholine molecules were incorporated into the membrane by incubation of the red cells at 22 degrees C with sonicated spin-labed phosphatidylcholine vesicles from which all traces of free fatty acids and lyso derivatives were carefully removed by bovine serum albumin treatment. This incorporation did not provide any change in the morphology of the cell as indicated by scanning electron microscopy. When spin-labeled phosphatidylcholine, having a nitroxide on the beta chain but near the polar head-group, was incorporated into the erythrocyte membrane, ascorbate treatment at 0 degrees C allows selective reduction of the signal coming from the outer layer of the membrane. When the label was on the polar head-group, the inner content of the erythrocyte rapidly reduced the label facing the cytoplasm, thus creaging a spontaneous anisotropy of the labeling. The anisotropic distribution of spin-labeled phosphatidylcholine in the erythrocyte membrane was found to be stable at 22 and 37 degrees C for more than 4 h. It is therefore concluded that the rate of outside-inside and inside-outside transition is so slow that the anisotropic distribution of the phospholipids in the erythrocyte membrane can be maintained during cell life."} {"id": "PMID:178362", "title": "Study of the transverse diffusion of spin-labeled phospholipids in biological membranes. II. Inner mitochondrial membrane of rat liver: use of phosphatidylcholine exchange protein.", "content": "Spin-labeled phosphatidylcholine was incorporated into the membrane of isolated \"inner membrane+matrix\" particles of rat liver mitochondria by incubation with sonicated spin-labeled phosphatidylcholine vesicles at 22 degrees C. When the spin label was on the acyl chain the incorporation of phosphatidylcholine into the membrane was stimulated by the presence of the phosphatidylcholine exchange protein extracted from rat or beef liver. On the other hand no stimulation was observed when the nitroxide was on the polar head-group. When spin-labeled phosphatidycholine was incorporated into the mitochondrial membrane in the absence of phosphatidylcholine exchange protein, ascorbate treatment at 0 degrees C reduced the EPR signal of the spin-labeled membranes by approximately 50%, indicating that fusion incorporates molecules equally on both sides of the membrane. On the other hand when spin-labeled phosphatidylcholine was incorporated in the presence of the exchange protein most of the EPR signal could be destroyed by the ascorbate treatment at 0 degrees C, indicating that the spin-labeled phosphatidylcholine had been selectively incorporated in the outer layer of the membrane. Finally when the label is on the polar head-group the inner content of mitochondria reduces the label facing the matrix, thus creating again an anisotropy of the labeling. The anisotropic distribution of spin-labeled phosphatidylcholine in the mitochondrial membrane was found to be stable at 25 degrees C for more than 2 h. It is therefore concluded that the rate of outside-inside and inside-outside transitions are extremely slow (half-life greater than 24 h).", "contents": "Study of the transverse diffusion of spin-labeled phospholipids in biological membranes. II. Inner mitochondrial membrane of rat liver: use of phosphatidylcholine exchange protein. Spin-labeled phosphatidylcholine was incorporated into the membrane of isolated \"inner membrane+matrix\" particles of rat liver mitochondria by incubation with sonicated spin-labeled phosphatidylcholine vesicles at 22 degrees C. When the spin label was on the acyl chain the incorporation of phosphatidylcholine into the membrane was stimulated by the presence of the phosphatidylcholine exchange protein extracted from rat or beef liver. On the other hand no stimulation was observed when the nitroxide was on the polar head-group. When spin-labeled phosphatidycholine was incorporated into the mitochondrial membrane in the absence of phosphatidylcholine exchange protein, ascorbate treatment at 0 degrees C reduced the EPR signal of the spin-labeled membranes by approximately 50%, indicating that fusion incorporates molecules equally on both sides of the membrane. On the other hand when spin-labeled phosphatidylcholine was incorporated in the presence of the exchange protein most of the EPR signal could be destroyed by the ascorbate treatment at 0 degrees C, indicating that the spin-labeled phosphatidylcholine had been selectively incorporated in the outer layer of the membrane. Finally when the label is on the polar head-group the inner content of mitochondria reduces the label facing the matrix, thus creating again an anisotropy of the labeling. The anisotropic distribution of spin-labeled phosphatidylcholine in the mitochondrial membrane was found to be stable at 25 degrees C for more than 2 h. It is therefore concluded that the rate of outside-inside and inside-outside transitions are extremely slow (half-life greater than 24 h)."} {"id": "PMID:178363", "title": "Regulation of uracil uptake in Escherichia coli by adenosine 3',5'-monophosphate.", "content": "Culture of a wild-type strain of Escherichia coli in the presence of cyclic AMP leads to an impairment of uracil uptake. Half maximum inhibition of uracil uptake was observed at 1.5 mM cyclic AMP. The effect seems to be specific since no inhibition was found in cultures supplemented with ATP, ADP or 5'-AMP. Similarly the inhibition was not observed in cultures of a mutant deficient in the cyclic AMP receptor protein. The inhibition in uracil uptake, found in bacteria cultured in the presence of cyclic AMP, is not a consequence of a reduction in the growth rate. On the other hand, this inhibition was observed only in cultures containing glucose or pyruvate as carbon source.", "contents": "Regulation of uracil uptake in Escherichia coli by adenosine 3',5'-monophosphate. Culture of a wild-type strain of Escherichia coli in the presence of cyclic AMP leads to an impairment of uracil uptake. Half maximum inhibition of uracil uptake was observed at 1.5 mM cyclic AMP. The effect seems to be specific since no inhibition was found in cultures supplemented with ATP, ADP or 5'-AMP. Similarly the inhibition was not observed in cultures of a mutant deficient in the cyclic AMP receptor protein. The inhibition in uracil uptake, found in bacteria cultured in the presence of cyclic AMP, is not a consequence of a reduction in the growth rate. On the other hand, this inhibition was observed only in cultures containing glucose or pyruvate as carbon source."} {"id": "PMID:178364", "title": "Concanavalin A stimulation modifies the lipid and protein structure or rabbit thymocyte plasma membranes. A laser raman study.", "content": "(1) We have compared the laser Raman spectra of isolated plasma membranes from resting rabbit thymocytes and cells mitogenically stimulated with concanavalin A. (2) Major alterations in the CH stretching, CH deformation and CC stretching regions indicate a different lipid architecture in the membranes from activated cells. (3) Spectral changes in the Amide I and II regions, by reference to the spectra of model compounds indicate greater protein amidation in the membranes from stimulated cells.", "contents": "Concanavalin A stimulation modifies the lipid and protein structure or rabbit thymocyte plasma membranes. A laser raman study. (1) We have compared the laser Raman spectra of isolated plasma membranes from resting rabbit thymocytes and cells mitogenically stimulated with concanavalin A. (2) Major alterations in the CH stretching, CH deformation and CC stretching regions indicate a different lipid architecture in the membranes from activated cells. (3) Spectral changes in the Amide I and II regions, by reference to the spectra of model compounds indicate greater protein amidation in the membranes from stimulated cells."} {"id": "PMID:178365", "title": "Motion of spin-labeled fatty acids in murine macrophages. Relation to cellular phagocytic activity.", "content": "Macrophage membrane fluidity was investigated with respect to cellular phagocytic activity through the use of fatty acid spin labels. Spin-labeled fatty acid derivatives were incorporated into intact mouse peritoneal macrophages by exchange from bovine serum albumin. The electron spin resonance (ESR) spectra of the spin-labeled fatty acids in the macrophages showed a pronounced temperature dependence and a decrease in the hyperfine splittings (2 T11) of the spectra as the nitroxide radical was moved away from the polar head group of the fatty acid derivatives. Spin-labeled macrophages underwent a time- and temperature-dependent decay, which was inhibited by preincubating the cells with mercuric chloride, heating at 56 degrees C, or by fixing them with 0.25% glutaraldehyde. No correlation between the phagocytic activity of macrophages and membrane freedom of motion could be demonstrated. Treatment of macrophages with anti-macrophage serum or extended in vitro cultivation inhibited cellular phagocytic activity but exerted no effect on the motional freedom of the macrophage membrane. Enrichment of the fatty acid composition of the macrophage membrane with cis- or trans-unsaturated fatty acids had striking effects on cellular phagocytic activity, while no significant changes could be detected in the freedom of motion of incorporated fatty acid spin labels at the degree of specific enrichment achieved here. Thus no correlation between cellular phagocytic activity and lipid motion could be detected.", "contents": "Motion of spin-labeled fatty acids in murine macrophages. Relation to cellular phagocytic activity. Macrophage membrane fluidity was investigated with respect to cellular phagocytic activity through the use of fatty acid spin labels. Spin-labeled fatty acid derivatives were incorporated into intact mouse peritoneal macrophages by exchange from bovine serum albumin. The electron spin resonance (ESR) spectra of the spin-labeled fatty acids in the macrophages showed a pronounced temperature dependence and a decrease in the hyperfine splittings (2 T11) of the spectra as the nitroxide radical was moved away from the polar head group of the fatty acid derivatives. Spin-labeled macrophages underwent a time- and temperature-dependent decay, which was inhibited by preincubating the cells with mercuric chloride, heating at 56 degrees C, or by fixing them with 0.25% glutaraldehyde. No correlation between the phagocytic activity of macrophages and membrane freedom of motion could be demonstrated. Treatment of macrophages with anti-macrophage serum or extended in vitro cultivation inhibited cellular phagocytic activity but exerted no effect on the motional freedom of the macrophage membrane. Enrichment of the fatty acid composition of the macrophage membrane with cis- or trans-unsaturated fatty acids had striking effects on cellular phagocytic activity, while no significant changes could be detected in the freedom of motion of incorporated fatty acid spin labels at the degree of specific enrichment achieved here. Thus no correlation between cellular phagocytic activity and lipid motion could be detected."} {"id": "PMID:178366", "title": "Characterization of the parathyrin receptor in renal plasma membranes by labelled hormone and labelled antibody binding techniques.", "content": "The parathyrin receptor in renal cortex has been investigated by studying the binding of 125I-labelled parathyrin, or of unlabelled parathyrin detected with 125I-labelled antibodies, to a partially purified plasma membrane fraction. The kinetics of hormone uptake demonstrated a biphasic response in both systems at 22 degrees C but this phenomenon was not detectable at 37 degrees C. Specific displacement of lactoperoxidase labelled 125I-labelled parathyrin occurred with 8 ng unlabelled bovine parathyrin. The apparent affinity constant was 2.3-10(8) M(-1) and the apparent binding capacity of the membranes 1.25 pmol/mg protein. Using the labelled antibody technique the receptor showed maximal binding at pH 7.0-7.5. As little as 80 pg bovine parathyrin produced a significant increase in binding of labelled anti-bovine parathyrin antibody and saturation of binding sites was demonstrated at 2.5 pmol/mg protein. Oxidized hormone showed undetectable binding. Treatment of membranes with phospholipases A or D, or Trypsin greatly reduced subsequent hormone binding. Prior incubation of membranes with 1-34 synthetic parathyrin decreased the binding of intact hormone whereas gastrin, insulin and glucagon had no effect. Growth hormone and calcitonin slightly increased parathyrin binding.", "contents": "Characterization of the parathyrin receptor in renal plasma membranes by labelled hormone and labelled antibody binding techniques. The parathyrin receptor in renal cortex has been investigated by studying the binding of 125I-labelled parathyrin, or of unlabelled parathyrin detected with 125I-labelled antibodies, to a partially purified plasma membrane fraction. The kinetics of hormone uptake demonstrated a biphasic response in both systems at 22 degrees C but this phenomenon was not detectable at 37 degrees C. Specific displacement of lactoperoxidase labelled 125I-labelled parathyrin occurred with 8 ng unlabelled bovine parathyrin. The apparent affinity constant was 2.3-10(8) M(-1) and the apparent binding capacity of the membranes 1.25 pmol/mg protein. Using the labelled antibody technique the receptor showed maximal binding at pH 7.0-7.5. As little as 80 pg bovine parathyrin produced a significant increase in binding of labelled anti-bovine parathyrin antibody and saturation of binding sites was demonstrated at 2.5 pmol/mg protein. Oxidized hormone showed undetectable binding. Treatment of membranes with phospholipases A or D, or Trypsin greatly reduced subsequent hormone binding. Prior incubation of membranes with 1-34 synthetic parathyrin decreased the binding of intact hormone whereas gastrin, insulin and glucagon had no effect. Growth hormone and calcitonin slightly increased parathyrin binding."} {"id": "PMID:178367", "title": "Energy-dependent Mn2+ and Ca2+ uptake by the embryonic chick chorioallantoic membrane.", "content": "The chick chorioallantoic membrane is an epithelial tissue which actively transports large amounts of Ca2+ during embryonic development. In this paper Mn2+ uptake by the tissue was studied and compared to Ca2+ uptake in parallel experiments. The purpose of these experiments was to determine if Mn2+ could be used to gain more information about the Ca2+ transport system. It was found that Mn2+ uptake was reduced significantly under conditions that reduced Ca2+ uptake and that Mn2+, like Ca2+, was taken up preferentially by the ectodermal side of the tissue. Mn2+ uptake showed saturation kinetics with a Km of 0.33 MM. Mn2+ uptake was also competitively inhibited by Ca2+, and Ca2+ uptake inhibited by Mn2+. Electron microprobe studies showed that Mn2+ was localized in the ectoderm of the tissue in the same way as Ca2+. It was concluded from these studies that significant amounts of Mn2+ were accumulated by the active Ca2+ transport mechanism and that Mn2+ could be useful paramagnetic probe of divalent cation transport in this tissue.", "contents": "Energy-dependent Mn2+ and Ca2+ uptake by the embryonic chick chorioallantoic membrane. The chick chorioallantoic membrane is an epithelial tissue which actively transports large amounts of Ca2+ during embryonic development. In this paper Mn2+ uptake by the tissue was studied and compared to Ca2+ uptake in parallel experiments. The purpose of these experiments was to determine if Mn2+ could be used to gain more information about the Ca2+ transport system. It was found that Mn2+ uptake was reduced significantly under conditions that reduced Ca2+ uptake and that Mn2+, like Ca2+, was taken up preferentially by the ectodermal side of the tissue. Mn2+ uptake showed saturation kinetics with a Km of 0.33 MM. Mn2+ uptake was also competitively inhibited by Ca2+, and Ca2+ uptake inhibited by Mn2+. Electron microprobe studies showed that Mn2+ was localized in the ectoderm of the tissue in the same way as Ca2+. It was concluded from these studies that significant amounts of Mn2+ were accumulated by the active Ca2+ transport mechanism and that Mn2+ could be useful paramagnetic probe of divalent cation transport in this tissue."} {"id": "PMID:178368", "title": "Gramicidin S-synthetase. Electrophoretic characterization of the multienzyme.", "content": "1. A method characterizing the fully active gramicidin S-synthetase (EC. 6.3.2.-) multienzyme in protein mixtures by a combination of sedimentation and polyacrylamide gel electrophoretic mobility data has been described. 2. The molecular weight of 280000 has been reevaluated by gradient centrifugation, gel filtration, and polyacrylamide gel electrophoresis in presence of sodium dodecyl sulfate. The size of the multienzyme is not changed by sodium dodecyl sulfate treatment. 3. In polyacrylamide gel electrophoresis dimerisation occurs in Tris, while two bands, which may represent monomer and dimer, are observed in phosphate. 4. Reliability of molecular weight determinations of sodium dodecyl sulfate-protein complexes of sizes up to 300000 daltons has been determined, correlating either mobilities or retardation coefficients.", "contents": "Gramicidin S-synthetase. Electrophoretic characterization of the multienzyme. 1. A method characterizing the fully active gramicidin S-synthetase (EC. 6.3.2.-) multienzyme in protein mixtures by a combination of sedimentation and polyacrylamide gel electrophoretic mobility data has been described. 2. The molecular weight of 280000 has been reevaluated by gradient centrifugation, gel filtration, and polyacrylamide gel electrophoresis in presence of sodium dodecyl sulfate. The size of the multienzyme is not changed by sodium dodecyl sulfate treatment. 3. In polyacrylamide gel electrophoresis dimerisation occurs in Tris, while two bands, which may represent monomer and dimer, are observed in phosphate. 4. Reliability of molecular weight determinations of sodium dodecyl sulfate-protein complexes of sizes up to 300000 daltons has been determined, correlating either mobilities or retardation coefficients."} {"id": "PMID:178369", "title": "Gramicidin S-synthetase. A further characterization of phenylalanine racemase, the light enzyme of gramicidin s-synthetase.", "content": "1. Chromatography on hydroxyapatite and on aminohexyl-Sepharose as well as isoelectric focusing were introduced as new effective purification procedures for phenylalanine racemase (EC 5.1.1.11). The enzyme preparations obtained were essentially homogeneous, as demonstrated by specific activity measurements and polyacrylamide gel electrophoresis. 2. The enzyme is not dissociable by sodium dodecyl sulfate. 3. Phenylalanine racemase is an acidic protein with an isoelectric point of approx. 4.6 (isoelectric focusing). 4. The Michaelis constants of L-Phe and D-Phe in the aminoacyl adenylate activation are 0.06 and 0.13 mM, respectively. 5. From our studies with structural analogues of phenylalanine we infer that the amino group of this amino acid is essential for its binding to the aminoacyl adenylate reaction center. The carboxyl group is not at all or only weakly bound. The benzene ring of phenylalanine which determines substrate recognition also seems to be of minor importance for substrate binding.", "contents": "Gramicidin S-synthetase. A further characterization of phenylalanine racemase, the light enzyme of gramicidin s-synthetase. 1. Chromatography on hydroxyapatite and on aminohexyl-Sepharose as well as isoelectric focusing were introduced as new effective purification procedures for phenylalanine racemase (EC 5.1.1.11). The enzyme preparations obtained were essentially homogeneous, as demonstrated by specific activity measurements and polyacrylamide gel electrophoresis. 2. The enzyme is not dissociable by sodium dodecyl sulfate. 3. Phenylalanine racemase is an acidic protein with an isoelectric point of approx. 4.6 (isoelectric focusing). 4. The Michaelis constants of L-Phe and D-Phe in the aminoacyl adenylate activation are 0.06 and 0.13 mM, respectively. 5. From our studies with structural analogues of phenylalanine we infer that the amino group of this amino acid is essential for its binding to the aminoacyl adenylate reaction center. The carboxyl group is not at all or only weakly bound. The benzene ring of phenylalanine which determines substrate recognition also seems to be of minor importance for substrate binding."} {"id": "PMID:178370", "title": "Affinity chromatography of thiamin pyrophosphokinase of rat brain.", "content": "Affinity column chromatography coupled with thiamin monophosphate absorbs thiamin pyrophosphokinase activity in the crude extract of rat brain, and the enzyme can be eluted from the column by 0.01 mM thiamin with approximately 700-fold purification.", "contents": "Affinity chromatography of thiamin pyrophosphokinase of rat brain. Affinity column chromatography coupled with thiamin monophosphate absorbs thiamin pyrophosphokinase activity in the crude extract of rat brain, and the enzyme can be eluted from the column by 0.01 mM thiamin with approximately 700-fold purification."} {"id": "PMID:178371", "title": "Studies on inosine monophosphate dehydrogenase. Steady state kinetics.", "content": "The reaction catalyzed by IMP dehydrogenase (IMP: NAD+ oxidoreductase EC 1.2.1.14) from Aerobacter aerogenes has been investigated kinetically at pH 8.1 as a three reactant system by means of steady-state velocity studies in the absence of products, as well as by inhibition studies using products and substrate analogues. The mechanism appears to be a partially random one in which IMP and K+ can bind randomly to the free enzyme while NAD does not react unless K+ or both K+ and IMP are present on the enzyme. While the steady-state velocity data can be analysed adequately on the basis that rapid equilibrium conditions apply, this is only an approximate description of the mechanism since product inhibition studies indicate that there is a significant concentration of an enzyme-XMP (enzyme-K-XMP) complex in the steady-state.", "contents": "Studies on inosine monophosphate dehydrogenase. Steady state kinetics. The reaction catalyzed by IMP dehydrogenase (IMP: NAD+ oxidoreductase EC 1.2.1.14) from Aerobacter aerogenes has been investigated kinetically at pH 8.1 as a three reactant system by means of steady-state velocity studies in the absence of products, as well as by inhibition studies using products and substrate analogues. The mechanism appears to be a partially random one in which IMP and K+ can bind randomly to the free enzyme while NAD does not react unless K+ or both K+ and IMP are present on the enzyme. While the steady-state velocity data can be analysed adequately on the basis that rapid equilibrium conditions apply, this is only an approximate description of the mechanism since product inhibition studies indicate that there is a significant concentration of an enzyme-XMP (enzyme-K-XMP) complex in the steady-state."} {"id": "PMID:178372", "title": "Folates as inhibitors of glutamate dehydrogenase.", "content": "Folates and tetrahydrofolates inhibit beef liver glutamate dehydrogenase (EC 1.4.1.2). Double reciprocal plats indicate a competitive inhibition for alpha-ketoglutarate-glutamate by folic acid and methotrexate and a complex or mixed type for NAD-NADH site. Pteroic acid is not inhibitory at the concentrations studied. The addition of up to four gamma-linked glutamyl residues to folic and tetrahydrofolic acids increases the inhibition. Further chain elongation of the gamma-peptide had no effect on the inhibitory activity. The p-aminobenzoate poly-gamma-glutamates were less inhibitory than the corresponding folyl polyglutamates.", "contents": "Folates as inhibitors of glutamate dehydrogenase. Folates and tetrahydrofolates inhibit beef liver glutamate dehydrogenase (EC 1.4.1.2). Double reciprocal plats indicate a competitive inhibition for alpha-ketoglutarate-glutamate by folic acid and methotrexate and a complex or mixed type for NAD-NADH site. Pteroic acid is not inhibitory at the concentrations studied. The addition of up to four gamma-linked glutamyl residues to folic and tetrahydrofolic acids increases the inhibition. Further chain elongation of the gamma-peptide had no effect on the inhibitory activity. The p-aminobenzoate poly-gamma-glutamates were less inhibitory than the corresponding folyl polyglutamates."} {"id": "PMID:178373", "title": "Protein kinases and their substrates in brown adipose tissue from newborn rats.", "content": "The 10000 X g supernatant fraction of brown fat from newborn rats catalyzed the cyclic AMP-dependent phosphorylation of both histone and a preparation of proteins from the same subcellular fraction (endogenous proteins). The apparent affinity for ATP was lower for the phosphorylation of the endogenous proteins than for the phosphorylation of histone. In order to discover whether the phosphorylation of histone and the endogenous proteins were catalyzed by different enzymes, the 100000 X g supernatant was fractionated by ion-exchange and adsorption chromatography. Three different cyclic AMP-dependent protein kinases and one cyclic AMP-independent protein kinase were separated and partially purified. Each of these enzymes catalyzed the phosphorylation of both substrates, and the difference in apparent Km for ATP remained. Neither affinity chromatography on histone-Sepharose, nor electrophoresis on polyacrylamide gels resulted in the separation of the phosphorylation of histone from that of the endogenous proteins of any of the partially purified kinases. Moreover, experiments in which the phosphorylated substrates were separated by differential precipitation with trichloroacetic acid showed that the endogenous proteins competitively inhibited the phosphorylation of lysine-rich histone. It is concluded that each of the partially purified kinase preparations contains protein kinase, which catalyzes the phosphorylation of both substrates. The difference in apparent Km for ATP was found to be due to the presence in the endogenous protein preparation of a low molecular weight compound which competes with ATP. This was not ATP nor the modulator protein. The ratio of the phosphorylation of endogenous proteins to that of histone was much higher for the cyclic AMP-independent kinase preparation than for the other enzymes. Electrophoresis of the endogenous substrates in the presence of sodium dodecyl sulphate showed that the enzyme phosphorylated a greater number of proteins than did the cyclic AMP-dependent kinases. The phosphorylation of endogenous proteins relative to that of histone was significantly lower for one of the cyclic AMP-dependent kinases than for the other two. This difference was not reflected in a different pattern of phosphorylation of the individual proteins of the endogenous mixture.", "contents": "Protein kinases and their substrates in brown adipose tissue from newborn rats. The 10000 X g supernatant fraction of brown fat from newborn rats catalyzed the cyclic AMP-dependent phosphorylation of both histone and a preparation of proteins from the same subcellular fraction (endogenous proteins). The apparent affinity for ATP was lower for the phosphorylation of the endogenous proteins than for the phosphorylation of histone. In order to discover whether the phosphorylation of histone and the endogenous proteins were catalyzed by different enzymes, the 100000 X g supernatant was fractionated by ion-exchange and adsorption chromatography. Three different cyclic AMP-dependent protein kinases and one cyclic AMP-independent protein kinase were separated and partially purified. Each of these enzymes catalyzed the phosphorylation of both substrates, and the difference in apparent Km for ATP remained. Neither affinity chromatography on histone-Sepharose, nor electrophoresis on polyacrylamide gels resulted in the separation of the phosphorylation of histone from that of the endogenous proteins of any of the partially purified kinases. Moreover, experiments in which the phosphorylated substrates were separated by differential precipitation with trichloroacetic acid showed that the endogenous proteins competitively inhibited the phosphorylation of lysine-rich histone. It is concluded that each of the partially purified kinase preparations contains protein kinase, which catalyzes the phosphorylation of both substrates. The difference in apparent Km for ATP was found to be due to the presence in the endogenous protein preparation of a low molecular weight compound which competes with ATP. This was not ATP nor the modulator protein. The ratio of the phosphorylation of endogenous proteins to that of histone was much higher for the cyclic AMP-independent kinase preparation than for the other enzymes. Electrophoresis of the endogenous substrates in the presence of sodium dodecyl sulphate showed that the enzyme phosphorylated a greater number of proteins than did the cyclic AMP-dependent kinases. The phosphorylation of endogenous proteins relative to that of histone was significantly lower for one of the cyclic AMP-dependent kinases than for the other two. This difference was not reflected in a different pattern of phosphorylation of the individual proteins of the endogenous mixture."} {"id": "PMID:178374", "title": "Thiophosphate-activated phosphorylase kinase as a probe in the regulation of phosphorylase phosphatase.", "content": "Rabbit muscle nonactivated phosphorylase kinase (EC 2.7.1.38) is converted to thiophosphate-activated phosphorylase kinase by cyclic AMP dependent protein kinase, Mg2+ and ATP-gamma-S/adenosine-5'-O-(s-thiotriphosphate)/. The formation of thiophosphate-activated phosphorylase kinase wal also observed in the protein-glycogen complex from skeletal muscle. This new form of kinase is resistant to the action of phosphatase and behaves as a competitive inhibitor in the dephosphorylation of phosphorylase alpha by phosphorylase phosphatase (Ki = 0.04 mg per ml). The fact that the inhibitory effect of thiophosphate-activated phosphorylase kinase is 3 times higher than in the case of nonactivated kinase, may explain the transient inhibition of phosphorylase phosphatase in the protein-glycogen complex. The use of activated (phosphorylated) phosphorylase kinase supports this assumption since it causes a delay in the dephosphorylation of phosphorylase alpha, i.e. the conversion of phosphorylase alpha into beta could start only after the dephosphorylation of activated phosphorylase kinase.", "contents": "Thiophosphate-activated phosphorylase kinase as a probe in the regulation of phosphorylase phosphatase. Rabbit muscle nonactivated phosphorylase kinase (EC 2.7.1.38) is converted to thiophosphate-activated phosphorylase kinase by cyclic AMP dependent protein kinase, Mg2+ and ATP-gamma-S/adenosine-5'-O-(s-thiotriphosphate)/. The formation of thiophosphate-activated phosphorylase kinase wal also observed in the protein-glycogen complex from skeletal muscle. This new form of kinase is resistant to the action of phosphatase and behaves as a competitive inhibitor in the dephosphorylation of phosphorylase alpha by phosphorylase phosphatase (Ki = 0.04 mg per ml). The fact that the inhibitory effect of thiophosphate-activated phosphorylase kinase is 3 times higher than in the case of nonactivated kinase, may explain the transient inhibition of phosphorylase phosphatase in the protein-glycogen complex. The use of activated (phosphorylated) phosphorylase kinase supports this assumption since it causes a delay in the dephosphorylation of phosphorylase alpha, i.e. the conversion of phosphorylase alpha into beta could start only after the dephosphorylation of activated phosphorylase kinase."} {"id": "PMID:178375", "title": "Collagenolytic activity from isolated bone cells.", "content": "A true collagenase (EC 3.4.24.3) which had been discovered previously in bone culture fluids and extracts of whole bone has now been localized to the cellular component of bone. The cellular enzyme bears the same characteristics as that of bone collagenases described earlier. Moreover, it is directly extractable in relatively large quantities. Attempts to demonstrate the presence of a bone cell procollagease were unsuccessful. It was also observed that the cells secrete significant amounts of collagenase in vitro. With increasing incubation time the extracellular collagenase levels rise and the intracellular collagenase levels drop.", "contents": "Collagenolytic activity from isolated bone cells. A true collagenase (EC 3.4.24.3) which had been discovered previously in bone culture fluids and extracts of whole bone has now been localized to the cellular component of bone. The cellular enzyme bears the same characteristics as that of bone collagenases described earlier. Moreover, it is directly extractable in relatively large quantities. Attempts to demonstrate the presence of a bone cell procollagease were unsuccessful. It was also observed that the cells secrete significant amounts of collagenase in vitro. With increasing incubation time the extracellular collagenase levels rise and the intracellular collagenase levels drop."} {"id": "PMID:178376", "title": "Purification and characterization of phosphodiesterase I from Bothrops atrox.", "content": "Phosphodiesterase I from the venom of Bothrops atrox has been purified by successive chromatography on phosphocellulose P-11, hydroxyapatite, and DEAE-cellulose DE 52. The final product gave a single band on sodium dodecylsulfate-polyacrylamide gels and was free of endonuclease, 5' -nucleotidase, and unspecific alkaline phosphatase activity. It was concentrated in an Amicon ultrafiltrator without loss of activity and could be stored in 10 mM magnesium acetate and 10% glycerol at 4 degrees C for at least a year. Under optimal conditions, the enzyme reaction required 15 mM Mg2+ and a pH of 9.2. Phosphodiesterase I is relatively thermostable and, in the presence of a macromolecular substrate, was not denatured after 4 h at 55 degrees C. The pure enzyme offers new possibilities for sequence studies on highly structured nucleic acids at elevated temperatures.", "contents": "Purification and characterization of phosphodiesterase I from Bothrops atrox. Phosphodiesterase I from the venom of Bothrops atrox has been purified by successive chromatography on phosphocellulose P-11, hydroxyapatite, and DEAE-cellulose DE 52. The final product gave a single band on sodium dodecylsulfate-polyacrylamide gels and was free of endonuclease, 5' -nucleotidase, and unspecific alkaline phosphatase activity. It was concentrated in an Amicon ultrafiltrator without loss of activity and could be stored in 10 mM magnesium acetate and 10% glycerol at 4 degrees C for at least a year. Under optimal conditions, the enzyme reaction required 15 mM Mg2+ and a pH of 9.2. Phosphodiesterase I is relatively thermostable and, in the presence of a macromolecular substrate, was not denatured after 4 h at 55 degrees C. The pure enzyme offers new possibilities for sequence studies on highly structured nucleic acids at elevated temperatures."} {"id": "PMID:178377", "title": "Identification of DNA in the core component of avian myeloblastosis virus.", "content": "Avian myeloblastosis virus (AMV) was found to contain DNA associated with the virion. The viral envelope was removed by treating the virus with a nonionic detergent and the DNA was found in the core fraction. These experiments indicate that the DNA associated with tumor virus is not contaminant associated with the viral envelope and suggest that the DNA is part of the internal core component. The DNA from avian myeloblastosis virus has a density of 1.70 g/cm3.", "contents": "Identification of DNA in the core component of avian myeloblastosis virus. Avian myeloblastosis virus (AMV) was found to contain DNA associated with the virion. The viral envelope was removed by treating the virus with a nonionic detergent and the DNA was found in the core fraction. These experiments indicate that the DNA associated with tumor virus is not contaminant associated with the viral envelope and suggest that the DNA is part of the internal core component. The DNA from avian myeloblastosis virus has a density of 1.70 g/cm3."} {"id": "PMID:178378", "title": "Electron transfer between protein and DNA in gamma-irradiated deoxyribonucleoprotein.", "content": "When deoxyribonucleoprotein-proflavine complexes were studied by electron spin-resonance spectroscopy following gamma-irradiation, it was found that stable free radicals were not formed at random on the complex but were preferentially located on proflavine. Since proflavine intercalalated to DNA bases serves as a final acceptor of electrons liberated by ionization, the result of our experiment was regarded as suggesting that the electron transfer from the protein moiety to the DNA moiety occurred in the irradiated deoxyribonucleoprotein.", "contents": "Electron transfer between protein and DNA in gamma-irradiated deoxyribonucleoprotein. When deoxyribonucleoprotein-proflavine complexes were studied by electron spin-resonance spectroscopy following gamma-irradiation, it was found that stable free radicals were not formed at random on the complex but were preferentially located on proflavine. Since proflavine intercalalated to DNA bases serves as a final acceptor of electrons liberated by ionization, the result of our experiment was regarded as suggesting that the electron transfer from the protein moiety to the DNA moiety occurred in the irradiated deoxyribonucleoprotein."} {"id": "PMID:178379", "title": "Repair replication in human cells. Simplified determination utilizing hydroxyurea.", "content": "A simplified and shortened procedure has been developed for the determination of repair replication of DNA in cultured mammalian cells. The procedure, using the bromodeoxyuridine density label and a radio-isotopic label has been applied to normal diploid human cells (WI38) and to their SV40 transformants (VA13). After incubation with the repair label the cells are lysed and digested for two hours at 50 degrees C with proteinase K. This digest can then be immediately subjected to alkaline cesium chloride density gradient centrifugation with no need for DNA extraction. Hydroxyurea is used to reduce the level of semi-conservative synthesis that a quantitative determination of repair replication can be accomplished by a single centrifugation. The method is not affected by variation in the effectiveness of the inhibitor although a small amount of semi-conservative synthesis normally occurs in the presence of the drug. The time course of repair replication in WI38 cells is unaffected by the drug. The apparent amount of repair synthesis in ultraviolet irradiated cells is increased 25 to 40% in the presence of hydroxyurea when thymidine is used as tracer. Under certain conditions in which the level of semiconservative synthesis is low (e.g., contact inhibited cells, high ultraviolet doses) the use of hydroxyurea is unnecessary.", "contents": "Repair replication in human cells. Simplified determination utilizing hydroxyurea. A simplified and shortened procedure has been developed for the determination of repair replication of DNA in cultured mammalian cells. The procedure, using the bromodeoxyuridine density label and a radio-isotopic label has been applied to normal diploid human cells (WI38) and to their SV40 transformants (VA13). After incubation with the repair label the cells are lysed and digested for two hours at 50 degrees C with proteinase K. This digest can then be immediately subjected to alkaline cesium chloride density gradient centrifugation with no need for DNA extraction. Hydroxyurea is used to reduce the level of semi-conservative synthesis that a quantitative determination of repair replication can be accomplished by a single centrifugation. The method is not affected by variation in the effectiveness of the inhibitor although a small amount of semi-conservative synthesis normally occurs in the presence of the drug. The time course of repair replication in WI38 cells is unaffected by the drug. The apparent amount of repair synthesis in ultraviolet irradiated cells is increased 25 to 40% in the presence of hydroxyurea when thymidine is used as tracer. Under certain conditions in which the level of semiconservative synthesis is low (e.g., contact inhibited cells, high ultraviolet doses) the use of hydroxyurea is unnecessary."} {"id": "PMID:178380", "title": "Possible interaction of cyclic nucleotides with the prolactin stimulation of casein synthesis in mouse mammary gland explants.", "content": "During a 10-h incubation, cyclic nucleotide phosphodiesterase inhibitors, viz. theophylline and quinine, were found to reduce by 40-50% the rate of [3H] leucine incorporation into casein in mammary gland explants from midpregnant mice. Further, dibutyryl cyclic AMP as well as the phosphodiesterase inhibitors were found to abolish the prolactin stimulation of leucine incorporation into casein. Elevated levels of cyclic AMP therefore appear to impair the functionality of the mammary gland. Although cyclic GMP was previously shown to stimulate RNA synthesis in the mammary gland in a prolactin-like manner, it had no effect on the rate of casein synthesis in mammary gland explants. Preincubation of explants with cyclic GMP did, however, attenuate the time required for the commencement of the prolactin stimulation of the rate of leucine incorporation into casein. A physiological role of cyclic GMP for the regulation of the rate of casein synthesis is thus suggested.", "contents": "Possible interaction of cyclic nucleotides with the prolactin stimulation of casein synthesis in mouse mammary gland explants. During a 10-h incubation, cyclic nucleotide phosphodiesterase inhibitors, viz. theophylline and quinine, were found to reduce by 40-50% the rate of [3H] leucine incorporation into casein in mammary gland explants from midpregnant mice. Further, dibutyryl cyclic AMP as well as the phosphodiesterase inhibitors were found to abolish the prolactin stimulation of leucine incorporation into casein. Elevated levels of cyclic AMP therefore appear to impair the functionality of the mammary gland. Although cyclic GMP was previously shown to stimulate RNA synthesis in the mammary gland in a prolactin-like manner, it had no effect on the rate of casein synthesis in mammary gland explants. Preincubation of explants with cyclic GMP did, however, attenuate the time required for the commencement of the prolactin stimulation of the rate of leucine incorporation into casein. A physiological role of cyclic GMP for the regulation of the rate of casein synthesis is thus suggested."} {"id": "PMID:178384", "title": "Tryptophan 2,3-dioxygenase: a review of the roles of the heme and copper cofactors in catalysis.", "content": "L-Tryptophan, 2,3-dioxygenase (EC 1.13.11.11) has been purified to homogenity from L-tryptophan induced Pseudomonas acidovorans (ATCC 11299b) and from L-tryptophan and cortisone induced rat liver. The enzyme from both sources is composed of four subunits and contains two g-atoms copper and two moles heme per mole tetramer. The proteins from the two sources are not identical. Three oxidation states of tryptophan oxygenase have been isolated: (1) fully oxidized, [Cu(II)]2[Ferriheme]2; (2) half reduced, [Cu(i)]2[ferriheme]2; and (3) fully reduced, [Cu(I)]2[ferroheme]2. Catalytic activity is dependent solely on the presence of Cu(I) in the enzyme, the heme may be either ferro or ferri. The presence of Cu(II) in the enzyme results in a requirement for an exogenous reductant, such as ascorbate, in order to elicit enzymic activity. Ligands, such as cyanide and carbon monoxide, can inhibit catalysis by binding to either or to both the copper and heme moieties. Metal complexing agents, such as bathocuproinesulfonate and bathophenanthrolinesulfonate, can inhibit catalysis by binding to Cu(I) resent only in catalytically active enzyme molecules. During catalysis by the fully reduced form of the enzyme, molecular oxygen binds to the heme moieties, while during catalysis by the half reduced form of the enzyme it does not, presumably binding instead to the Cu(I) moieties. Enzymes that catalyze similar reactions have been purified from other sources. Indoleamine 2,3-dioxygenase appears to be a heme protein, but its copper content is unknown. Pyrrolooxygenases appear to be completely different enzymes, although they have not yet been purified to homegeneity.", "contents": "Tryptophan 2,3-dioxygenase: a review of the roles of the heme and copper cofactors in catalysis. L-Tryptophan, 2,3-dioxygenase (EC 1.13.11.11) has been purified to homogenity from L-tryptophan induced Pseudomonas acidovorans (ATCC 11299b) and from L-tryptophan and cortisone induced rat liver. The enzyme from both sources is composed of four subunits and contains two g-atoms copper and two moles heme per mole tetramer. The proteins from the two sources are not identical. Three oxidation states of tryptophan oxygenase have been isolated: (1) fully oxidized, [Cu(II)]2[Ferriheme]2; (2) half reduced, [Cu(i)]2[ferriheme]2; and (3) fully reduced, [Cu(I)]2[ferroheme]2. Catalytic activity is dependent solely on the presence of Cu(I) in the enzyme, the heme may be either ferro or ferri. The presence of Cu(II) in the enzyme results in a requirement for an exogenous reductant, such as ascorbate, in order to elicit enzymic activity. Ligands, such as cyanide and carbon monoxide, can inhibit catalysis by binding to either or to both the copper and heme moieties. Metal complexing agents, such as bathocuproinesulfonate and bathophenanthrolinesulfonate, can inhibit catalysis by binding to Cu(I) resent only in catalytically active enzyme molecules. During catalysis by the fully reduced form of the enzyme, molecular oxygen binds to the heme moieties, while during catalysis by the half reduced form of the enzyme it does not, presumably binding instead to the Cu(I) moieties. Enzymes that catalyze similar reactions have been purified from other sources. Indoleamine 2,3-dioxygenase appears to be a heme protein, but its copper content is unknown. Pyrrolooxygenases appear to be completely different enzymes, although they have not yet been purified to homegeneity."} {"id": "PMID:178386", "title": "Analysis of estrogen glucuronides. I--Characterization of estrogen glucuronides by gas chromatography mass spectrometry.", "content": "The mass spectral characterization of nine kinds of estrogen glucuronides was investigated. The glucuronides were analysed after conversion to n-propyl ester-O-TMS ether derivatives by gas chromatography mass spectrometry. The fragmentation of these derivatives is discussed using deuterium labels and TMS-d9 imidazole. A clear-cut difference was found between aliphatic and aromatic glucuronic acid conjugates. In particular the [M - 362]+- fragment ion was characteristic in the mass spectra of estrogen 3-glucuronides. On the other hand, four isomers of estriol and 16-epiestriol glucuronides containing an aliphatic acetal linkage were also characterized by the fragment ions of m/e value 204, 345, 415, and 431 and their relative intensities. Thus, all nine estrogen glucuronides were discriminated mass spectrometrically.", "contents": "Analysis of estrogen glucuronides. I--Characterization of estrogen glucuronides by gas chromatography mass spectrometry. The mass spectral characterization of nine kinds of estrogen glucuronides was investigated. The glucuronides were analysed after conversion to n-propyl ester-O-TMS ether derivatives by gas chromatography mass spectrometry. The fragmentation of these derivatives is discussed using deuterium labels and TMS-d9 imidazole. A clear-cut difference was found between aliphatic and aromatic glucuronic acid conjugates. In particular the [M - 362]+- fragment ion was characteristic in the mass spectra of estrogen 3-glucuronides. On the other hand, four isomers of estriol and 16-epiestriol glucuronides containing an aliphatic acetal linkage were also characterized by the fragment ions of m/e value 204, 345, 415, and 431 and their relative intensities. Thus, all nine estrogen glucuronides were discriminated mass spectrometrically."} {"id": "PMID:178387", "title": "Characterization of sand as a support for immobilized enzymes.", "content": "The potential of sand as a support for immobilized enzymes was investigated by preparing alkylamine sand and devising methods to measure the total number of amine groups present and the fraction available for immobilization of enzymes. Alcohol dehydrogenase (alcohol: NAD oxidoreductase, EC 1.1.1.1.) and lactate dehydrogenase (L-lactate:NAD oxidoreductase, EC 1.1.1.27) were immobilized on alkylamine sand, and the stability of the immobilized protein and dehydrogenase activity was measured. Urease (urea amidohydrolase, EC 3.5.1.5) was also immobilized on sand to test the applicability of these methods to larger scale immobilizations. Results suggest that sand shows promise as a support for immobilized enzymes.", "contents": "Characterization of sand as a support for immobilized enzymes. The potential of sand as a support for immobilized enzymes was investigated by preparing alkylamine sand and devising methods to measure the total number of amine groups present and the fraction available for immobilization of enzymes. Alcohol dehydrogenase (alcohol: NAD oxidoreductase, EC 1.1.1.1.) and lactate dehydrogenase (L-lactate:NAD oxidoreductase, EC 1.1.1.27) were immobilized on alkylamine sand, and the stability of the immobilized protein and dehydrogenase activity was measured. Urease (urea amidohydrolase, EC 3.5.1.5) was also immobilized on sand to test the applicability of these methods to larger scale immobilizations. Results suggest that sand shows promise as a support for immobilized enzymes."} {"id": "PMID:178388", "title": "[Activity of energy metabolism related enzymes in the myocardium and liver following administration of large doses of noradrenaline].", "content": "The activity of the glycolytic enzymes and of the glucose-6-phosphate dehydrogenase (G-6-PDH) were compared with the content of noradrenaline in rat myocardium and the liver after the intraperitoneal injection of high doses of noradrenaline. It was shown that 24 hours after int noradrenaline injection which caused exhaustion of endogenous catecholamine supply, the lactate content and the activities of lactic dehydrogenase were increased in the myocardium; the activity of hexokinase and G-6-PDH in rat myocardium and the liver were also increased, whereas the glucokinase activity was decreased. In these experiments alterations of the enzyme activities were shown to be similar to the alterations in the dystrophic tissues in which the catecholamine content was sharply decreased. The role of the sympathetic nervous system and its mediators in the mechanism of the enzyme regulation of the energy metabolism in the myocardium and the liver is discussed.", "contents": "[Activity of energy metabolism related enzymes in the myocardium and liver following administration of large doses of noradrenaline]. The activity of the glycolytic enzymes and of the glucose-6-phosphate dehydrogenase (G-6-PDH) were compared with the content of noradrenaline in rat myocardium and the liver after the intraperitoneal injection of high doses of noradrenaline. It was shown that 24 hours after int noradrenaline injection which caused exhaustion of endogenous catecholamine supply, the lactate content and the activities of lactic dehydrogenase were increased in the myocardium; the activity of hexokinase and G-6-PDH in rat myocardium and the liver were also increased, whereas the glucokinase activity was decreased. In these experiments alterations of the enzyme activities were shown to be similar to the alterations in the dystrophic tissues in which the catecholamine content was sharply decreased. The role of the sympathetic nervous system and its mediators in the mechanism of the enzyme regulation of the energy metabolism in the myocardium and the liver is discussed."} {"id": "PMID:178383", "title": "[Lipid oxidation in bilayer lipid membranes linked with the reaction of oxidation of NAD.H by atmospheric oxygen].", "content": "It is shown that along with NAD.H oxidation with air oxygen peroxide oxidation of lipids forming the membrane takes place in bilayer lipid membranes modified with ubiquinone. During nicotin amide oxidation proton absorption takes place. Peroxide oxidation of lipids results in the liberation of H+ ions, which in its turn brings about the formation of protone-deficient or enriched (against aqueous solution) layers adjacent to the membrane. The potential value on the membrane is shown to depend on nicotine amide and oxygen concentration, on ubiquinone presence and lipid composition of the membrane. It has been also indicated that the transmembrane potential difference is initiated with a sharp change of aqueous solution pH by 0.05--0.4 units.", "contents": "[Lipid oxidation in bilayer lipid membranes linked with the reaction of oxidation of NAD.H by atmospheric oxygen]. It is shown that along with NAD.H oxidation with air oxygen peroxide oxidation of lipids forming the membrane takes place in bilayer lipid membranes modified with ubiquinone. During nicotin amide oxidation proton absorption takes place. Peroxide oxidation of lipids results in the liberation of H+ ions, which in its turn brings about the formation of protone-deficient or enriched (against aqueous solution) layers adjacent to the membrane. The potential value on the membrane is shown to depend on nicotine amide and oxygen concentration, on ubiquinone presence and lipid composition of the membrane. It has been also indicated that the transmembrane potential difference is initiated with a sharp change of aqueous solution pH by 0.05--0.4 units."} {"id": "PMID:178389", "title": "[Pyruvate kinase activity in the liver of rats with induced tumors].", "content": "M-isozyme pyruvate kinase activity proved to be elevated in the liver of rats with hepatoma induced by p-dimethylaminoazobenzene. Sodium fluoride surplus in rat diet prevented the increase of this isozyme activity.", "contents": "[Pyruvate kinase activity in the liver of rats with induced tumors]. M-isozyme pyruvate kinase activity proved to be elevated in the liver of rats with hepatoma induced by p-dimethylaminoazobenzene. Sodium fluoride surplus in rat diet prevented the increase of this isozyme activity."} {"id": "PMID:178395", "title": "Implicit-shape constancy as a factor in pictorial perception.", "content": "Schoolboys from the Ivory Coast and from Kenya were tested on a simple task intended to detect the effect of implicit-shape constancy. The presence of such an effect was confirmed. Comparison of two Ivorean subsamples differing in their responses to a request to build a model of a depicted structure showed that those subjects who build flat (2D) models were less influenced by the implicit-shape constancy than those subjects who built three-dimensional structures. This confirms a postulated link between the implicit constancy and perception of pictorial depth.", "contents": "Implicit-shape constancy as a factor in pictorial perception. Schoolboys from the Ivory Coast and from Kenya were tested on a simple task intended to detect the effect of implicit-shape constancy. The presence of such an effect was confirmed. Comparison of two Ivorean subsamples differing in their responses to a request to build a model of a depicted structure showed that those subjects who build flat (2D) models were less influenced by the implicit-shape constancy than those subjects who built three-dimensional structures. This confirms a postulated link between the implicit constancy and perception of pictorial depth."} {"id": "PMID:178396", "title": "Enzyme inhibition in colorectal surgery.", "content": "Anastomotic dehiscence is particularly common after low anterior resection of the rectum. The enzyme collagenase is largely responsible for this high complication rate. Inhibition of this enzyme in an experimental model produced significantly stronger colonic anastomoses. There may be a place for such an inhibitor in clinical surgery.", "contents": "Enzyme inhibition in colorectal surgery. Anastomotic dehiscence is particularly common after low anterior resection of the rectum. The enzyme collagenase is largely responsible for this high complication rate. Inhibition of this enzyme in an experimental model produced significantly stronger colonic anastomoses. There may be a place for such an inhibitor in clinical surgery."} {"id": "PMID:178397", "title": "The treatment of mixed parotid tumours by enucleation and radiotherapy.", "content": "A series of mixed parotid tumours treated by simple enucleation and radiotherapy between 1962 and 1968 is discussed. There were 73 primary and 8 recurrent cases. Only 2 small recurrences occurred in the 73 primary cases, although 4 other patients were lost to follow-up after 7 years or more. In the 8 recurrent cases, 7 had been treated elsewhere by enucleation alone, thus confirming the opinion that this operation is frequently unsuccessful. Treatment was by further local excision and radiotherapy and no recurrences have occurred. The view is therefore expressed that simple enucleation and radiotherapy is the treatment of choice in all primary mixed parotid tumours.", "contents": "The treatment of mixed parotid tumours by enucleation and radiotherapy. A series of mixed parotid tumours treated by simple enucleation and radiotherapy between 1962 and 1968 is discussed. There were 73 primary and 8 recurrent cases. Only 2 small recurrences occurred in the 73 primary cases, although 4 other patients were lost to follow-up after 7 years or more. In the 8 recurrent cases, 7 had been treated elsewhere by enucleation alone, thus confirming the opinion that this operation is frequently unsuccessful. Treatment was by further local excision and radiotherapy and no recurrences have occurred. The view is therefore expressed that simple enucleation and radiotherapy is the treatment of choice in all primary mixed parotid tumours."} {"id": "PMID:178398", "title": "Ovarian tumours in childhood: a 27-year review.", "content": "Twenty-five children treated for ovarian neoplasms at the Royal Hospital for Sick Children, Yorkhill,Glasgow, between 1947 and 1974 are reported. Eight of the patients had malignant tumours and 17 benign. The patients with benign tumours were treated by either salpingo-oophorectomy or oophorectomy. The malignant cases were treated with either surgery alone or in combination with deep X-ray therapy and/or chemotherapy. Two patients died of malignant teratoma, but the remaining 6 with malignant teratoma, dysgerminoma or endodermal sinus are well. The management of these patients is discussed.", "contents": "Ovarian tumours in childhood: a 27-year review. Twenty-five children treated for ovarian neoplasms at the Royal Hospital for Sick Children, Yorkhill,Glasgow, between 1947 and 1974 are reported. Eight of the patients had malignant tumours and 17 benign. The patients with benign tumours were treated by either salpingo-oophorectomy or oophorectomy. The malignant cases were treated with either surgery alone or in combination with deep X-ray therapy and/or chemotherapy. Two patients died of malignant teratoma, but the remaining 6 with malignant teratoma, dysgerminoma or endodermal sinus are well. The management of these patients is discussed."} {"id": "PMID:178399", "title": "Plasma cyclic adenosine-3', 5'-monophosphate response to glucagon in patients with liver disease.", "content": "The change in plasma cyclic adenosine-3', 5'-monophosphate (AMP) was measured after intravenous injection of 1 mg of glucagon in 10 normal subjects and 30 patients with various forms of liver disease. Patients with cirrhosis and those with intrahepatic cholestasis responded normally but in patients with extrahepatic obstruction the plasma cyclic AMP response was considerably increased. Six of the eight patients with cirrhosis and a surgically created portacaval shunt had very reduced responses. This test may prove to be diagnostically important, particularly in differentiating surgical from non-surgical jaundice.", "contents": "Plasma cyclic adenosine-3', 5'-monophosphate response to glucagon in patients with liver disease. The change in plasma cyclic adenosine-3', 5'-monophosphate (AMP) was measured after intravenous injection of 1 mg of glucagon in 10 normal subjects and 30 patients with various forms of liver disease. Patients with cirrhosis and those with intrahepatic cholestasis responded normally but in patients with extrahepatic obstruction the plasma cyclic AMP response was considerably increased. Six of the eight patients with cirrhosis and a surgically created portacaval shunt had very reduced responses. This test may prove to be diagnostically important, particularly in differentiating surgical from non-surgical jaundice."} {"id": "PMID:178405", "title": "Attachment of gonococci to sperm. Influence of physical and chemical factors.", "content": "Neisseria gonorrhoeae of pilated T1 and nonpilated T4 colony types attached themselves to human sperm in greatest numbers and most reproducibly when suspensions of the cells were incubated at 35 degrees C in Ringer's solution, pH 6-8. After incubation for 15 or 30 min. in a water bath shaker, 50 per cent. of human sperm had T1 gonococci attached and 25 per cent. T4. Sperm and both types of gonococci were pre-incubated separately with various chemical agents, selected because the agent is found in genital fluids, or has a known effect on bacterial cell walls or sperm membrane. After treatment, sperm were washed or were not washed, and were then tested for attachment by mixture with untreated gonococci. Treated gonococci were handled in the same manner. Change in the percentage of attachment was defined as deviation from the range expected on the basis of a standard curve. Treatment of sperm with the nucleotides, ATP or cAMP, curtailed attachment by T1 gonococci but had no effect on attachment by T4.", "contents": "Attachment of gonococci to sperm. Influence of physical and chemical factors. Neisseria gonorrhoeae of pilated T1 and nonpilated T4 colony types attached themselves to human sperm in greatest numbers and most reproducibly when suspensions of the cells were incubated at 35 degrees C in Ringer's solution, pH 6-8. After incubation for 15 or 30 min. in a water bath shaker, 50 per cent. of human sperm had T1 gonococci attached and 25 per cent. T4. Sperm and both types of gonococci were pre-incubated separately with various chemical agents, selected because the agent is found in genital fluids, or has a known effect on bacterial cell walls or sperm membrane. After treatment, sperm were washed or were not washed, and were then tested for attachment by mixture with untreated gonococci. Treated gonococci were handled in the same manner. Change in the percentage of attachment was defined as deviation from the range expected on the basis of a standard curve. Treatment of sperm with the nucleotides, ATP or cAMP, curtailed attachment by T1 gonococci but had no effect on attachment by T4."} {"id": "PMID:178406", "title": "Penicillin decreases chloride conductance in crustacean muscle: a model for the epileptic neuron.", "content": "The effects of penicillin were studied on the neuromuscular preparation of the ghost crab, Ocypoda cursor. Penicillin in doses lower than 2 mM reduced both the amplitude of inhibitory junction potentials and conductance increases induced by external application of GABA. The nature of the latter effect appears to be 2-fold, a weaker competitive inhibition and a more powerful non-competitive effech which may be ionophore blockade. Penicillin in concentrations above 2 mM diminished resting conductance, especially that of chloride. The action of penicillin is, in general, to decrease chloride conductance in this preparation. The crustacean neuromuscular preparation may provide a useful analogue for understanding penicillin evoked epilepsy. The reduced chloride conductance could explain decreased inhibition, increased excitation and depolarization shifts in cortical neurons.", "contents": "Penicillin decreases chloride conductance in crustacean muscle: a model for the epileptic neuron. The effects of penicillin were studied on the neuromuscular preparation of the ghost crab, Ocypoda cursor. Penicillin in doses lower than 2 mM reduced both the amplitude of inhibitory junction potentials and conductance increases induced by external application of GABA. The nature of the latter effect appears to be 2-fold, a weaker competitive inhibition and a more powerful non-competitive effech which may be ionophore blockade. Penicillin in concentrations above 2 mM diminished resting conductance, especially that of chloride. The action of penicillin is, in general, to decrease chloride conductance in this preparation. The crustacean neuromuscular preparation may provide a useful analogue for understanding penicillin evoked epilepsy. The reduced chloride conductance could explain decreased inhibition, increased excitation and depolarization shifts in cortical neurons."} {"id": "PMID:178407", "title": "Reduced glucocorticoid binding site concentration in cortical neuronal perikarya from senescent rats.", "content": "Isolated neuronal perikarya from cerebral cortices of senescent (24-26-month-old) male rats exhibit a 55-65% reduction in the concentration of specific cytosol glucocorticoid binding sites when compared to mature counterparts (12-13 months). Neuronal preparations from the two age groups are essentially identical with respect to yield, protein content, physiochemical integrity and purity as judged by enrichment for free glycine and reduction in carbonic anhydrase specific activity (relative to unfractionated cortical cell suspensions). Adrenalectomy does not alter the number of glucocorticoid binding sites in either group, and age differences do not appear due to differential partitioning of sites between nucleus and cytoplasm. It is suggested that loss of receptors from the cortical neuron population represents a possible mechanism by which glucocorticoid responsiveness may be decreased during aging.", "contents": "Reduced glucocorticoid binding site concentration in cortical neuronal perikarya from senescent rats. Isolated neuronal perikarya from cerebral cortices of senescent (24-26-month-old) male rats exhibit a 55-65% reduction in the concentration of specific cytosol glucocorticoid binding sites when compared to mature counterparts (12-13 months). Neuronal preparations from the two age groups are essentially identical with respect to yield, protein content, physiochemical integrity and purity as judged by enrichment for free glycine and reduction in carbonic anhydrase specific activity (relative to unfractionated cortical cell suspensions). Adrenalectomy does not alter the number of glucocorticoid binding sites in either group, and age differences do not appear due to differential partitioning of sites between nucleus and cytoplasm. It is suggested that loss of receptors from the cortical neuron population represents a possible mechanism by which glucocorticoid responsiveness may be decreased during aging."} {"id": "PMID:178408", "title": "Cytochemical localization of cyclic 3', 5'-nucleotide phosphodiesterase activity in the neuromuscular junction and skeletal muscle of the newt.", "content": "The localization of cyclic 3', 5'-nucleotide phosphodiesterase activity at the neuromuscular junction and in skeletal muscle of the newt was studied cytochemically. In the axon terminal, activity was localized to a site on the membranes of synaptic vesicles. In skeletal muscle, activity occurred in the sarcoplasmic reticulum but was restricted to the longitudinal tubules. Junctional folds of the motor end plate were unreactive. These findings are suggestive of a role of cyclic AMP in the functions of synaptic vesicles and sarcoplasmic reticulum and indicate its effects are terminated at these sites.", "contents": "Cytochemical localization of cyclic 3', 5'-nucleotide phosphodiesterase activity in the neuromuscular junction and skeletal muscle of the newt. The localization of cyclic 3', 5'-nucleotide phosphodiesterase activity at the neuromuscular junction and in skeletal muscle of the newt was studied cytochemically. In the axon terminal, activity was localized to a site on the membranes of synaptic vesicles. In skeletal muscle, activity occurred in the sarcoplasmic reticulum but was restricted to the longitudinal tubules. Junctional folds of the motor end plate were unreactive. These findings are suggestive of a role of cyclic AMP in the functions of synaptic vesicles and sarcoplasmic reticulum and indicate its effects are terminated at these sites."} {"id": "PMID:178409", "title": "Climbing fiver activation and 3', 5'-cyclic guanosine monophosphate (cGMP) content in cortex and deep nuclei of cerebellum.", "content": "Harmaline (28 mumoles/kg u.v.), cold exposure (4C) or isoniazid (2.2 mmoles/kg s.c.) increased the cGMP content in rat cerebellar cortex several fold. Isoniazid but not harmaline or cold exposure increased cGMP in the deep cerebellar nuclei (nuclei interpositus, vestibularis and fastigius) and striatum. In rats treated with the nicotinamide antagonist 3-acetylpyridine (3-AP) (0.66 mumoles/kg i.p. 4 days before) the tremorogenic effect of harmaline and the increase of cerebellar cortex cGMP produced by this alkaloid was abated. Similarly the increase of cGMP following exposure to cold was reduced. In contrast isoniazid and glutamate (10 mumoles intraventricularly) increased cGMP to the same extent in control and 3-AP treated rats. Since 3-AP produces in rat a massive degeneration of the inferior olivary nucleus and of the climbing fibers but leaves intact all the other cerebellar elements, these experiments suggest that an increase of cGMP content in postsynaptic cerebellar elements (presumable Purkinje cells) may be an expression of an increased release of an excitatory transmitter from either the climbing fivers or the parallel fibers.", "contents": "Climbing fiver activation and 3', 5'-cyclic guanosine monophosphate (cGMP) content in cortex and deep nuclei of cerebellum. Harmaline (28 mumoles/kg u.v.), cold exposure (4C) or isoniazid (2.2 mmoles/kg s.c.) increased the cGMP content in rat cerebellar cortex several fold. Isoniazid but not harmaline or cold exposure increased cGMP in the deep cerebellar nuclei (nuclei interpositus, vestibularis and fastigius) and striatum. In rats treated with the nicotinamide antagonist 3-acetylpyridine (3-AP) (0.66 mumoles/kg i.p. 4 days before) the tremorogenic effect of harmaline and the increase of cerebellar cortex cGMP produced by this alkaloid was abated. Similarly the increase of cGMP following exposure to cold was reduced. In contrast isoniazid and glutamate (10 mumoles intraventricularly) increased cGMP to the same extent in control and 3-AP treated rats. Since 3-AP produces in rat a massive degeneration of the inferior olivary nucleus and of the climbing fibers but leaves intact all the other cerebellar elements, these experiments suggest that an increase of cGMP content in postsynaptic cerebellar elements (presumable Purkinje cells) may be an expression of an increased release of an excitatory transmitter from either the climbing fivers or the parallel fibers."} {"id": "PMID:178410", "title": "The action of norepinephrine in the rat hippocampus. III. Hippocampal cellular responses to locus coeruleus stimulation in the awake rat.", "content": "The behavioral and physiological effects of electrical stimulation of the nucleus locus coeruleus (LC) were studied in the awake rat. LC electrodes consistently supported high rates of self-stimulation (SS). LC stimulation also inhibited spontaneous cellular discharges in the hippocampus (HPC). Both the LC-induced inhibition of HPC units and the LC-evoked SS behavior were antagonized by alpha-methyltyrosine and 6-hydroxydopamine. In addition, chlorpromazine and diethyldithiocarbamate antagonized LC-induced inhibition of HPC units. D-Amphetamine facilitated SS behavior and reduced spontaneous HPC unit activity. The reinforcing properties of LC stimulation correlate closely with inhibition of cellular activity in the hippocampus; both actions appear to be mediated by norepinephrine.", "contents": "The action of norepinephrine in the rat hippocampus. III. Hippocampal cellular responses to locus coeruleus stimulation in the awake rat. The behavioral and physiological effects of electrical stimulation of the nucleus locus coeruleus (LC) were studied in the awake rat. LC electrodes consistently supported high rates of self-stimulation (SS). LC stimulation also inhibited spontaneous cellular discharges in the hippocampus (HPC). Both the LC-induced inhibition of HPC units and the LC-evoked SS behavior were antagonized by alpha-methyltyrosine and 6-hydroxydopamine. In addition, chlorpromazine and diethyldithiocarbamate antagonized LC-induced inhibition of HPC units. D-Amphetamine facilitated SS behavior and reduced spontaneous HPC unit activity. The reinforcing properties of LC stimulation correlate closely with inhibition of cellular activity in the hippocampus; both actions appear to be mediated by norepinephrine."} {"id": "PMID:178411", "title": "The action of norepinephrine in the rat hippocampus. IV. The effects of locus coeruleus stimulation on evoked hippocampal unit activity.", "content": "Activity of neurons in the hippocampus (HPC) was recorded in awake, freely moving rats. Most cells were inhibited by either a loud auditory stimulus (tone) or by electrical stimulation of the nucleus locus coeruleus (LC). The inhibitory responses to the tone were antagonized by drugs that interfere with central noradrenergic transmission. When LC stimulation was used as the unconditioned stimulus in a classical conditioning paradigm, previously inhibitory responses to the tone were reinstituted. When behaviorally subthreshold LC stimulation preceded a tone which was correlated with food, the existing conditioned response to the tone was potentiated. These data suggest that the generalized inhibitory response of HPC neurons to a tone is modulated by the noradrenergic pathway and that experimental activation of LC can potentiate HPC responses to behaviorally significant conditioned stimuli.", "contents": "The action of norepinephrine in the rat hippocampus. IV. The effects of locus coeruleus stimulation on evoked hippocampal unit activity. Activity of neurons in the hippocampus (HPC) was recorded in awake, freely moving rats. Most cells were inhibited by either a loud auditory stimulus (tone) or by electrical stimulation of the nucleus locus coeruleus (LC). The inhibitory responses to the tone were antagonized by drugs that interfere with central noradrenergic transmission. When LC stimulation was used as the unconditioned stimulus in a classical conditioning paradigm, previously inhibitory responses to the tone were reinstituted. When behaviorally subthreshold LC stimulation preceded a tone which was correlated with food, the existing conditioned response to the tone was potentiated. These data suggest that the generalized inhibitory response of HPC neurons to a tone is modulated by the noradrenergic pathway and that experimental activation of LC can potentiate HPC responses to behaviorally significant conditioned stimuli."} {"id": "PMID:178413", "title": "[Subcellular localization of rat adipocyte lipoprotein lipase].", "content": "The sub-cellular localisation in rat fat cells of lipoprotein lipase is discussed in this paper. The lipoprotein lipase was found with maximum activity in the microsomal fraction. Some special features of this activity in membrane fraction are pointed out.", "contents": "[Subcellular localization of rat adipocyte lipoprotein lipase]. The sub-cellular localisation in rat fat cells of lipoprotein lipase is discussed in this paper. The lipoprotein lipase was found with maximum activity in the microsomal fraction. Some special features of this activity in membrane fraction are pointed out."} {"id": "PMID:178414", "title": "[Traumatic deciduoma and delayed nidation in castrated pregnant rat after ACTH injection].", "content": "After administration of ACTH it is possible to obtain traumatic deciduomata in rats ovariectomized during early pregnancy and delayed implantation in rats ovariectomized day 4 of pregnancy and injected dayly with oestradiol from day 8 or 9. The substance responsible seems to be Progesterone or Progesterone like corticoid.", "contents": "[Traumatic deciduoma and delayed nidation in castrated pregnant rat after ACTH injection]. After administration of ACTH it is possible to obtain traumatic deciduomata in rats ovariectomized during early pregnancy and delayed implantation in rats ovariectomized day 4 of pregnancy and injected dayly with oestradiol from day 8 or 9. The substance responsible seems to be Progesterone or Progesterone like corticoid."} {"id": "PMID:178415", "title": "[Supppression of paradoxical sleep by chloramphenicol. Absence of effect by thiamphenicol].", "content": "The oral administration of 160-250 mg/kg of chloramphenicol selectively suppresses Paradoxical Sleep in the cat for a duration of 10-20 hours. Larger doses (330 mg/kg) suppress Paradoxical Sleep for 27 hours, but aslso decrease Slow Wave Sleep. At the same dose, Thiamphenicol has no effect.", "contents": "[Supppression of paradoxical sleep by chloramphenicol. Absence of effect by thiamphenicol]. The oral administration of 160-250 mg/kg of chloramphenicol selectively suppresses Paradoxical Sleep in the cat for a duration of 10-20 hours. Larger doses (330 mg/kg) suppress Paradoxical Sleep for 27 hours, but aslso decrease Slow Wave Sleep. At the same dose, Thiamphenicol has no effect."} {"id": "PMID:178416", "title": "[Corticotrope and melanotrope cells in cat, fox, rat and human fetus adenohypophysis: studies with induced fluorescence, cytoimmunologic technics and lead hematoxyline].", "content": "Formaldehyde-induced fluorescence, acid-catalyzed or not, methods, and immunocytology with anti-ACTH (1-24), anti-ACTH(17-39), ANTI-BETA-LPH immunserums were applied on the same preparations of cat, fox, rat and human foetus pituitaries. The superpositions of results showed that the pars intermedia and pars distalis corticomelano-lipotrophic cells of fox and cat pituitary, those of human foetal pituitary, and the purely corticotrophics cells of the rat pars distalis contained a fluorogenic probably granular compound. Moreover, the granules of the same cell types were electively revealed on our lymphilized material by plombic hematoxylin. Only the anti-beta-LPH and/or anti-beta-MSH fixing celpls exhibited hypercyanophilic, PAS-positive and bleu alcian-positive caracteristics.", "contents": "[Corticotrope and melanotrope cells in cat, fox, rat and human fetus adenohypophysis: studies with induced fluorescence, cytoimmunologic technics and lead hematoxyline]. Formaldehyde-induced fluorescence, acid-catalyzed or not, methods, and immunocytology with anti-ACTH (1-24), anti-ACTH(17-39), ANTI-BETA-LPH immunserums were applied on the same preparations of cat, fox, rat and human foetus pituitaries. The superpositions of results showed that the pars intermedia and pars distalis corticomelano-lipotrophic cells of fox and cat pituitary, those of human foetal pituitary, and the purely corticotrophics cells of the rat pars distalis contained a fluorogenic probably granular compound. Moreover, the granules of the same cell types were electively revealed on our lymphilized material by plombic hematoxylin. Only the anti-beta-LPH and/or anti-beta-MSH fixing celpls exhibited hypercyanophilic, PAS-positive and bleu alcian-positive caracteristics."} {"id": "PMID:178417", "title": "[Effect of chronic hypoxia (Fi02 = 0.06 - Fi02 = 0.08) on mouse liver cytochrome P450 and b5 content].", "content": "During a eight days period of chronic hypoxia (FiO2 : 0,06) the cytochrome P 450 content of mice'liver decreases the 1st day, increases the 2nd and the 3rd day and decreases again and remains at a low levels. During a 13 days period of chronic hypoxia (FiO2 = 0,08) the P 450 level remains inchanged during 5 days. It decreases after until the 13teen day. G6Pase, an endoplasmic reticulum enzyme marker is quite inchanged in these conditions.", "contents": "[Effect of chronic hypoxia (Fi02 = 0.06 - Fi02 = 0.08) on mouse liver cytochrome P450 and b5 content]. During a eight days period of chronic hypoxia (FiO2 : 0,06) the cytochrome P 450 content of mice'liver decreases the 1st day, increases the 2nd and the 3rd day and decreases again and remains at a low levels. During a 13 days period of chronic hypoxia (FiO2 = 0,08) the P 450 level remains inchanged during 5 days. It decreases after until the 13teen day. G6Pase, an endoplasmic reticulum enzyme marker is quite inchanged in these conditions."} {"id": "PMID:178418", "title": "Studies on phosphoglyceromutase from chicken breast muscle: number and reactivity of sulfhydryl groups.", "content": "Phosphoglyceromutase (PGM) from chicken breast muscle was titrated with p-mercuribenzoate (PMB), 5,5'-dithiobisnitrobenzoate (Nbs2), N-ethylmaleimide (NEM), iodoacetate and iodoacetamide. The effect of all of the sulfhydryl reagents, with the exception of NEM was to cause a loss in enzymatic activity. Addition of KCN following reaction with Nbs2 resulted in the recovery of a small amount of enzymatic activity. In the absence of substrate (3-phosphoglyceric acid) or cofactor (2,3-diphosphoglyceric acid) and in the presence or absence of 6 M guanidine hydrochloride, six sulfhydryl groups per mole of enzyme were titrated with PMB.", "contents": "Studies on phosphoglyceromutase from chicken breast muscle: number and reactivity of sulfhydryl groups. Phosphoglyceromutase (PGM) from chicken breast muscle was titrated with p-mercuribenzoate (PMB), 5,5'-dithiobisnitrobenzoate (Nbs2), N-ethylmaleimide (NEM), iodoacetate and iodoacetamide. The effect of all of the sulfhydryl reagents, with the exception of NEM was to cause a loss in enzymatic activity. Addition of KCN following reaction with Nbs2 resulted in the recovery of a small amount of enzymatic activity. In the absence of substrate (3-phosphoglyceric acid) or cofactor (2,3-diphosphoglyceric acid) and in the presence or absence of 6 M guanidine hydrochloride, six sulfhydryl groups per mole of enzyme were titrated with PMB."} {"id": "PMID:178419", "title": "Biosynthesis of sphingomyelin in rat liver endoplasmic reticulum.", "content": "Rat liver microsomal sphingomyelin synthetase (CDPcholine: N-acylspingosine choline phosphotransferase (EC 2.7.8.3)) has been shown to be markedly stimulated by ATP and pantothenic acid derivatives such as CoA, pantethine, pantetheine and 4'-phosphopantetheine.", "contents": "Biosynthesis of sphingomyelin in rat liver endoplasmic reticulum. Rat liver microsomal sphingomyelin synthetase (CDPcholine: N-acylspingosine choline phosphotransferase (EC 2.7.8.3)) has been shown to be markedly stimulated by ATP and pantothenic acid derivatives such as CoA, pantethine, pantetheine and 4'-phosphopantetheine."} {"id": "PMID:178420", "title": "Studies of human papovavirus tumor antigen in experimental and human cerebral neoplasms.", "content": "Three types of papovaviruses (JC, BK, and SV40) have been isolated from man. All three are oncogenic in hamsters, cause frequent infection of man, and share a common T antigen. Augmentation of the expression of T antigen by in vitro cultivation of SV40-induced tumors of hamsters suggested that growing human brain tumors in vitro might provide an effective screening technique for the SV40 virus. In a series of human brain tumors examined in cryostat sections and in tissue culture, T antigen could not be demonstrated, suggesting that by this immunofluorescent technique SV40 was not implicated in the etiology of these tumors.", "contents": "Studies of human papovavirus tumor antigen in experimental and human cerebral neoplasms. Three types of papovaviruses (JC, BK, and SV40) have been isolated from man. All three are oncogenic in hamsters, cause frequent infection of man, and share a common T antigen. Augmentation of the expression of T antigen by in vitro cultivation of SV40-induced tumors of hamsters suggested that growing human brain tumors in vitro might provide an effective screening technique for the SV40 virus. In a series of human brain tumors examined in cryostat sections and in tissue culture, T antigen could not be demonstrated, suggesting that by this immunofluorescent technique SV40 was not implicated in the etiology of these tumors."} {"id": "PMID:178421", "title": "Hydatidiform mole metastasizing to the lung.", "content": "Pulmonary lesions developed in three patients with an invasive hydatidiform mole. At open thoracotomy the modules were found to contain molar tissue. Therapy with twice-weekly methotrexate induced complete clinical and biologic remission of the disease in all three patients.", "contents": "Hydatidiform mole metastasizing to the lung. Pulmonary lesions developed in three patients with an invasive hydatidiform mole. At open thoracotomy the modules were found to contain molar tissue. Therapy with twice-weekly methotrexate induced complete clinical and biologic remission of the disease in all three patients."} {"id": "PMID:178422", "title": "Nonimmunological host defenses: a review.", "content": "Nonimmunological defenses are very diverse in type. Some are directed against already transformed cells and belong to mechanisms of containment. Others exert a surveillance by preventing or inhibiting initial events of carcinogenesis. Chalones and oncolytic factors in sera and exudates are agents of containment. Under appropriate circumstances, the autoxidation of thiols and the formation of mixed disulfides lead to destruction of tumor cells in vitro and in vivo. Both processes involve the generation of superoxide radicals and of hydrogen peroxide which, in turn, activate the peroxide:peroxidase:halide system. Thiol:disulfide ratios and interchange codetermine the antioxidative activity of cellular membranes, thus bearing on carcinogenesis. Many aliphatic and aromatic antioxidants are endowed with anticarcinogenic properties. The fact that they are inhibitors of free radical processes corroborates the increasingly evident role of free radicals in carcinogenesis. Endogenous antioxidants and exogenous ones in foods are agents of surveillance. Antioxidant activity, linked with the ergastoplasm, points to a homeostatic mechanism that prevents self-accelerating chain reactions from leading to membrane damage or to carcinogenesis. Carcinogens can also be inactiviated by microsomal enzymes belonging to an overall mechanism of detoxification. Activity levels of these systems depend on diet and state of nutrition. They may be naturally very low, but they can be increased with various inducers.", "contents": "Nonimmunological host defenses: a review. Nonimmunological defenses are very diverse in type. Some are directed against already transformed cells and belong to mechanisms of containment. Others exert a surveillance by preventing or inhibiting initial events of carcinogenesis. Chalones and oncolytic factors in sera and exudates are agents of containment. Under appropriate circumstances, the autoxidation of thiols and the formation of mixed disulfides lead to destruction of tumor cells in vitro and in vivo. Both processes involve the generation of superoxide radicals and of hydrogen peroxide which, in turn, activate the peroxide:peroxidase:halide system. Thiol:disulfide ratios and interchange codetermine the antioxidative activity of cellular membranes, thus bearing on carcinogenesis. Many aliphatic and aromatic antioxidants are endowed with anticarcinogenic properties. The fact that they are inhibitors of free radical processes corroborates the increasingly evident role of free radicals in carcinogenesis. Endogenous antioxidants and exogenous ones in foods are agents of surveillance. Antioxidant activity, linked with the ergastoplasm, points to a homeostatic mechanism that prevents self-accelerating chain reactions from leading to membrane damage or to carcinogenesis. Carcinogens can also be inactiviated by microsomal enzymes belonging to an overall mechanism of detoxification. Activity levels of these systems depend on diet and state of nutrition. They may be naturally very low, but they can be increased with various inducers."} {"id": "PMID:178423", "title": "Corticosteroids and phosphatidylcholine biosynthesis in microsomal fractions from L5178Y lymphoma.", "content": "Microsomal fractions from mouse lymphoma L5178Y and from rat thymocytes were used to follow incorporation of radiolabel from cytidine diphosphate-[methyl-14C]choline into microsomal lipids. Dexamethasone, at concentrations ranging from 2.8 X 10(-6)M to 2.8 X 10(-5)M, partially inhibited this transfer reaction. Microsomes prepared from freshly isolated thymocytes were more sensitive to the effects of dexamethasone showing inhibition at concentrations of steroid as low as 2.8 X 10(-8)M. The inhibitory effect did not depend on the amount of the available endogenous diglycerides and was not related to a possible stimulation of cytidine diphosphate choline transferase back reaction by the steroid. The survey of a broad selection of different steroids revealed a lack of correlation between the known lymphocytolytic properties of steroids and their effects on cytidine diphosphate choline transferase. Dexamethasone was the only steroid of the glucocorticoid group that inhibited this reaction in microsomal fractions of L5178Y lymphoma. The structural requirement for the inhibitory effect was related to the absence of oxygen functions in positions 11 and 17 of the steroid and, possibly, to the presence of both C-20 and C-21 on the side chain.", "contents": "Corticosteroids and phosphatidylcholine biosynthesis in microsomal fractions from L5178Y lymphoma. Microsomal fractions from mouse lymphoma L5178Y and from rat thymocytes were used to follow incorporation of radiolabel from cytidine diphosphate-[methyl-14C]choline into microsomal lipids. Dexamethasone, at concentrations ranging from 2.8 X 10(-6)M to 2.8 X 10(-5)M, partially inhibited this transfer reaction. Microsomes prepared from freshly isolated thymocytes were more sensitive to the effects of dexamethasone showing inhibition at concentrations of steroid as low as 2.8 X 10(-8)M. The inhibitory effect did not depend on the amount of the available endogenous diglycerides and was not related to a possible stimulation of cytidine diphosphate choline transferase back reaction by the steroid. The survey of a broad selection of different steroids revealed a lack of correlation between the known lymphocytolytic properties of steroids and their effects on cytidine diphosphate choline transferase. Dexamethasone was the only steroid of the glucocorticoid group that inhibited this reaction in microsomal fractions of L5178Y lymphoma. The structural requirement for the inhibitory effect was related to the absence of oxygen functions in positions 11 and 17 of the steroid and, possibly, to the presence of both C-20 and C-21 on the side chain."} {"id": "PMID:178424", "title": "Histogenesis and growth pattern of 1,2-dimethylhydrazine-induced rat colon adenocarcinoma.", "content": "The histogenesis and growth pattern of colon adenocarcinoma have been studied using 74 BD IX rats given 20 mg 1,2-dimethylhydrazine hydrochloride per kg, s.c., weekly from Day 11 to their 24th week and serially sacrificed with controls. Modifications in DNA synthesis activity and early tumor changes were sought on histological and radioautographic preparations of normal-appearing colon mucosa. All visible colorectal tumors were analyzed for size, site, and pathology. Chronic dimethylhydrazine treatments resulted in a simultaneous increase in the number of both total and tritiated thymidine-labeled cells in the glands of Lieberk\u00fchn. In addition, microscopic carcinomatous foci were observed after the 15th week, and the first macroscopic adenocarcinomas appeared in 24-week-old animals. Their number thereafter exponentially increased with time. A total of 252 macroscopic tumors were obtained, of which 14 were classified as signet ring cell carcinomas and 238 as adenocarcinomas. Among the latter, local invasion could be documented in 230, including the smallest. No benign polypcancer sequence could be demonstrated in this material. The average growth pattern of those adenocarcinomas could be adequately described by a Gompertz curve, with a short initial doubling time (e.g., 7.5 days in 1.0-cu mm tumors) that progressively increases with time (e.g., 59.6 days in 5000-cu mm tumors).", "contents": "Histogenesis and growth pattern of 1,2-dimethylhydrazine-induced rat colon adenocarcinoma. The histogenesis and growth pattern of colon adenocarcinoma have been studied using 74 BD IX rats given 20 mg 1,2-dimethylhydrazine hydrochloride per kg, s.c., weekly from Day 11 to their 24th week and serially sacrificed with controls. Modifications in DNA synthesis activity and early tumor changes were sought on histological and radioautographic preparations of normal-appearing colon mucosa. All visible colorectal tumors were analyzed for size, site, and pathology. Chronic dimethylhydrazine treatments resulted in a simultaneous increase in the number of both total and tritiated thymidine-labeled cells in the glands of Lieberk\u00fchn. In addition, microscopic carcinomatous foci were observed after the 15th week, and the first macroscopic adenocarcinomas appeared in 24-week-old animals. Their number thereafter exponentially increased with time. A total of 252 macroscopic tumors were obtained, of which 14 were classified as signet ring cell carcinomas and 238 as adenocarcinomas. Among the latter, local invasion could be documented in 230, including the smallest. No benign polypcancer sequence could be demonstrated in this material. The average growth pattern of those adenocarcinomas could be adequately described by a Gompertz curve, with a short initial doubling time (e.g., 7.5 days in 1.0-cu mm tumors) that progressively increases with time (e.g., 59.6 days in 5000-cu mm tumors)."} {"id": "PMID:178425", "title": "Inhibited growth in vivo of a mouse pregnancy-dependent mammary tumor (TPDMT-4) by an antiestrogen, 2alpha, 3alpha-epithio-5alpha-androstan-17beta-ol (10275-S).", "content": "TPDMT-4 mammary tumors, characterized by growth during pregnancy and postpartum regression, grew continuously in DDD virgin mice carrying pituitary isografts or 17 beta-estradiol plus progesterone pellets. In the experimental models, effects of 2alpha,3alpha-epithio-5alpha-androstan-17beta-ol(10275-S), testosterone, and ovariectomy were investigated. When tumors implanted with pituitary isografts into the fat pad reached palpable volumes, animals were ovariectomized or received 5 s.c. injections of 100 mug to 1 mg 10275-S or 300 mug testosterone weekly. Tumors regressed immediately after ovariectomy or after the start of 10275-S treatment and after approximately the 10th day of testosterone treatment. Cystadenomatous morphology with strong secretory activity was noticed in treated animals. Tumor growth induced by 17beta-estradiol plus progesterone pellets was inhibited completely or partially by 3 s.c. injections of 50 to 500 mug 10275-S or 100 mug testosterone weekly starting from the day after tumor and 17beta-estradiol plus progesterone pellet implantation.", "contents": "Inhibited growth in vivo of a mouse pregnancy-dependent mammary tumor (TPDMT-4) by an antiestrogen, 2alpha, 3alpha-epithio-5alpha-androstan-17beta-ol (10275-S). TPDMT-4 mammary tumors, characterized by growth during pregnancy and postpartum regression, grew continuously in DDD virgin mice carrying pituitary isografts or 17 beta-estradiol plus progesterone pellets. In the experimental models, effects of 2alpha,3alpha-epithio-5alpha-androstan-17beta-ol(10275-S), testosterone, and ovariectomy were investigated. When tumors implanted with pituitary isografts into the fat pad reached palpable volumes, animals were ovariectomized or received 5 s.c. injections of 100 mug to 1 mg 10275-S or 300 mug testosterone weekly. Tumors regressed immediately after ovariectomy or after the start of 10275-S treatment and after approximately the 10th day of testosterone treatment. Cystadenomatous morphology with strong secretory activity was noticed in treated animals. Tumor growth induced by 17beta-estradiol plus progesterone pellets was inhibited completely or partially by 3 s.c. injections of 50 to 500 mug 10275-S or 100 mug testosterone weekly starting from the day after tumor and 17beta-estradiol plus progesterone pellet implantation."} {"id": "PMID:178426", "title": "Cell cycle-related hormone carcinogen interaction during chemical carcinogen induction of nodule-like mammary lesions in organ culture.", "content": "The immature mammary glands of BALB/c female mice were treated with 7,12-dimethylbenz[a]anthracene (DMBA), 2 micrograms/ml, or 3-methylcholanthrene (10 micrograms/ml) for a 24-hr period at different times during the inital six days of lobuloalveolar growth in hormone-supplemented organ culture. Nodule-like alveolar lesions (NLAL) were detectable in 80% of the glands treated with DMBA (40% in 3-methylcholanthrene-treated glands) in the presence of insulin + prolactin + aldosterone + cortisol in the medium. No NLAL were present in dimethyl sulfoxide-treated control glands cultivated with the same hormones. The hormone combination insulin + prolactin + cortisol was unfavorable for NLAL induction by DMBA, and the combination of aldosterone + insulin + prolactin was only moderately conducive. Thus, the presence of cortisol with insulin + prolactin + aldosterone enhances NLAL incidence of mammary cells by DMBA. The highest incidence was found in glands that were treated with DMBA for 24 hr between the third and fourth day of culture, the period corresponding to the onset of the second wave of DNA synthesis in the gland. Cytotoxicity of DMBA was pronounced between 24 and 48 hr, when a high frequency of cells were in DNA synthesis, and survival of the cells after the cytotoxic effect of DMBA appeared to play a role in NLAL incidence. This suggests that DMBA-induction of NLAL in mammary glands in organ culture involves a complex carcinogen-hormone-cell cycle interaction. We emphasize that, although NLAL morphologically resembles the hyperplastic alveolar nodules of mouse mammary gland in vivo, the abilitity of NLAL to produce typical hyperactive alveolar outgrowth and mammary tumor after transplantation iv vivo remains to be determined.", "contents": "Cell cycle-related hormone carcinogen interaction during chemical carcinogen induction of nodule-like mammary lesions in organ culture. The immature mammary glands of BALB/c female mice were treated with 7,12-dimethylbenz[a]anthracene (DMBA), 2 micrograms/ml, or 3-methylcholanthrene (10 micrograms/ml) for a 24-hr period at different times during the inital six days of lobuloalveolar growth in hormone-supplemented organ culture. Nodule-like alveolar lesions (NLAL) were detectable in 80% of the glands treated with DMBA (40% in 3-methylcholanthrene-treated glands) in the presence of insulin + prolactin + aldosterone + cortisol in the medium. No NLAL were present in dimethyl sulfoxide-treated control glands cultivated with the same hormones. The hormone combination insulin + prolactin + cortisol was unfavorable for NLAL induction by DMBA, and the combination of aldosterone + insulin + prolactin was only moderately conducive. Thus, the presence of cortisol with insulin + prolactin + aldosterone enhances NLAL incidence of mammary cells by DMBA. The highest incidence was found in glands that were treated with DMBA for 24 hr between the third and fourth day of culture, the period corresponding to the onset of the second wave of DNA synthesis in the gland. Cytotoxicity of DMBA was pronounced between 24 and 48 hr, when a high frequency of cells were in DNA synthesis, and survival of the cells after the cytotoxic effect of DMBA appeared to play a role in NLAL incidence. This suggests that DMBA-induction of NLAL in mammary glands in organ culture involves a complex carcinogen-hormone-cell cycle interaction. We emphasize that, although NLAL morphologically resembles the hyperplastic alveolar nodules of mouse mammary gland in vivo, the abilitity of NLAL to produce typical hyperactive alveolar outgrowth and mammary tumor after transplantation iv vivo remains to be determined."} {"id": "PMID:178427", "title": "Inactivation of tumor cell-associated feline oncornavirus for preparation of an infectious virus-free tumor cell immunogen.", "content": "Ultraviolet (UV) and thermal methods of inactivating the oncogenic potential of C-type particle-producing feline oncornavirus-induced tumor cells were developed. The techniques were evaluated by several parameters for their use in preparation of cellular immunogens. The UV inactivation dose required to reduce the number of focus-forming units per ml by 1 log10 for FL-74 lymphoblastoid cell-associated feline leukemia virus was 44,000 ergs/sq mm, and the thermal inactivation dose required to reduce the number of focus-forming units per ml by 1 log10 at 45 degrees was 16 min. Inactivation of greater than 6 log10 of virus per ml associated with 4 x 10(8) cells required a UV dose of 270,000 ergs/sq mm, 100 min at 45 degrees or 3 min at 56 degrees. All three treatments concomitantly destroyed the replicating potential of FL-74 cells as shown by their inability to propagate under normal growth conditions and to incorporate [3H]thymidine into nuclear DNA. UV inactivation and thermal inactivation at 45 degrees allowed the best retention of feline oncornavirus-associated cell membrane antigen. A 50% loss in antigenic activity was observed as a result of 56 degrees treatment, but this method was the only one that did not destroy the surface structural integrity of FL-74 cells.", "contents": "Inactivation of tumor cell-associated feline oncornavirus for preparation of an infectious virus-free tumor cell immunogen. Ultraviolet (UV) and thermal methods of inactivating the oncogenic potential of C-type particle-producing feline oncornavirus-induced tumor cells were developed. The techniques were evaluated by several parameters for their use in preparation of cellular immunogens. The UV inactivation dose required to reduce the number of focus-forming units per ml by 1 log10 for FL-74 lymphoblastoid cell-associated feline leukemia virus was 44,000 ergs/sq mm, and the thermal inactivation dose required to reduce the number of focus-forming units per ml by 1 log10 at 45 degrees was 16 min. Inactivation of greater than 6 log10 of virus per ml associated with 4 x 10(8) cells required a UV dose of 270,000 ergs/sq mm, 100 min at 45 degrees or 3 min at 56 degrees. All three treatments concomitantly destroyed the replicating potential of FL-74 cells as shown by their inability to propagate under normal growth conditions and to incorporate [3H]thymidine into nuclear DNA. UV inactivation and thermal inactivation at 45 degrees allowed the best retention of feline oncornavirus-associated cell membrane antigen. A 50% loss in antigenic activity was observed as a result of 56 degrees treatment, but this method was the only one that did not destroy the surface structural integrity of FL-74 cells."} {"id": "PMID:178428", "title": "Impaired host defense against XC cell-induced tumors in thymectomized and in bursectomized chickens.", "content": "XC cells originally derived from the tumor of a rat previously inoculated with the Prague strain of Rous sarcoma virus were used to induce tumors in chickens surgically thymectomized or bursectomized in the newly hatched period. Thymectomized chickens had a significantly higher incidence of tumors, larger tumors, and a higher tumor mortality, compared with control chickens, when both groups were given 5 X 10(6) XC cells into the wing webs. Bursectomy could significantly influence the tumor size only. It appeared that the capacity of XC cells to induce tumors and the growth of such tumors were subject to immunological influence, with the thymus playing a major and the bursa of Fabricus a minor role under the conditions used.", "contents": "Impaired host defense against XC cell-induced tumors in thymectomized and in bursectomized chickens. XC cells originally derived from the tumor of a rat previously inoculated with the Prague strain of Rous sarcoma virus were used to induce tumors in chickens surgically thymectomized or bursectomized in the newly hatched period. Thymectomized chickens had a significantly higher incidence of tumors, larger tumors, and a higher tumor mortality, compared with control chickens, when both groups were given 5 X 10(6) XC cells into the wing webs. Bursectomy could significantly influence the tumor size only. It appeared that the capacity of XC cells to induce tumors and the growth of such tumors were subject to immunological influence, with the thymus playing a major and the bursa of Fabricus a minor role under the conditions used."} {"id": "PMID:178429", "title": "Urinary excretion of cyclic guanosine 3':5'-monophosphate and cyclic adenosine 3':5'-monophosphate in rats bearing transplantable liver and kidney tumors.", "content": "Cyclic guanosine 3':5'-monophosphate (cyclic GMP) and cyclic adenosine 3':5-monophosphate were measured in the urine of normal rats and those bearing transplantable liver and kidney tumors. The level of cyclic GMP ranged from 1.4 to 1.6 mumoles/g urinary creatinine in several strains of rats without tumors. Rats bearing Morris hepatomas 20, 21, 9618A and 9633F and kidney tumor MK2 had urine levels of cyclic GMP from 1.3 to 3.6 mumoles/g creatinine. Rats bearing the fast growing hepatomas 9618A2 and 3924A and Morris kidney tumor MK3 had urinary values of 5.6. 41.9, and 32.7 mumoles cyclic GMP per g creatinine, respectively. Urine levels of cyclic adenosine 3':5'-monophosphate ranged from 10.1 to 19.7 mumoles/g creatinine in all normal and tumor-bearing rats and were not significantly different in any of the groups examined.", "contents": "Urinary excretion of cyclic guanosine 3':5'-monophosphate and cyclic adenosine 3':5'-monophosphate in rats bearing transplantable liver and kidney tumors. Cyclic guanosine 3':5'-monophosphate (cyclic GMP) and cyclic adenosine 3':5-monophosphate were measured in the urine of normal rats and those bearing transplantable liver and kidney tumors. The level of cyclic GMP ranged from 1.4 to 1.6 mumoles/g urinary creatinine in several strains of rats without tumors. Rats bearing Morris hepatomas 20, 21, 9618A and 9633F and kidney tumor MK2 had urine levels of cyclic GMP from 1.3 to 3.6 mumoles/g creatinine. Rats bearing the fast growing hepatomas 9618A2 and 3924A and Morris kidney tumor MK3 had urinary values of 5.6. 41.9, and 32.7 mumoles cyclic GMP per g creatinine, respectively. Urine levels of cyclic adenosine 3':5'-monophosphate ranged from 10.1 to 19.7 mumoles/g creatinine in all normal and tumor-bearing rats and were not significantly different in any of the groups examined."} {"id": "PMID:178430", "title": "Multilaminar endoplasmic reticulum and abnormal mitosis in Hodgkin tumor cells.", "content": "A multilaminar alteration of endoplasmic reticulum (ER) has been observed in tumor cells of eight patients with Hodgkin's disease and a patient with histiocytic lymphoma. These multilaminar structures are more numerous in dividing cells and thus appear to arise primarily during mitosis. The stacked membranes in the multilaminar structures possibly result from abnormal sticking of organelle membranes, as evidenced in this study of adherence of ER to other elements of ER, nuclear envelope, mitochondria, or lipid droplets. Multilaminar ER was identified in all mitotic tumor cells, a rare mitotic plasma cell, and numerous interphase Hodgkin cells. The paucity of multilaminar ER in normal mitotic cells and its virtual absence for normal interphase cells suggest that this structure represents a pathological alteration in tumor cells from patients with Hodgkin's disease and histiocytic lymphoma. The multilaminar defect of ER is associated with other atypical features of ER in Hodgkin tumor cells, including the excessive length and curving of ER profiles, the collapse of the ER cisternae, and the overall sparsity of this organelle. Other abnormalities observed in mitotic Hodgkin tumor cells include the presence of disorganized microtubules, large cytoplasmic vacuoles, and abnormally clumped chromosomal material and the persistence throughout mitosis of bodies suggestive of nucleoli and of the nuclear bodies of interphase cells.", "contents": "Multilaminar endoplasmic reticulum and abnormal mitosis in Hodgkin tumor cells. A multilaminar alteration of endoplasmic reticulum (ER) has been observed in tumor cells of eight patients with Hodgkin's disease and a patient with histiocytic lymphoma. These multilaminar structures are more numerous in dividing cells and thus appear to arise primarily during mitosis. The stacked membranes in the multilaminar structures possibly result from abnormal sticking of organelle membranes, as evidenced in this study of adherence of ER to other elements of ER, nuclear envelope, mitochondria, or lipid droplets. Multilaminar ER was identified in all mitotic tumor cells, a rare mitotic plasma cell, and numerous interphase Hodgkin cells. The paucity of multilaminar ER in normal mitotic cells and its virtual absence for normal interphase cells suggest that this structure represents a pathological alteration in tumor cells from patients with Hodgkin's disease and histiocytic lymphoma. The multilaminar defect of ER is associated with other atypical features of ER in Hodgkin tumor cells, including the excessive length and curving of ER profiles, the collapse of the ER cisternae, and the overall sparsity of this organelle. Other abnormalities observed in mitotic Hodgkin tumor cells include the presence of disorganized microtubules, large cytoplasmic vacuoles, and abnormally clumped chromosomal material and the persistence throughout mitosis of bodies suggestive of nucleoli and of the nuclear bodies of interphase cells."} {"id": "PMID:178431", "title": "Regulation of the adenylate cyclase system in transplantable hepatomas.", "content": "Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane.", "contents": "Regulation of the adenylate cyclase system in transplantable hepatomas. Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane."} {"id": "PMID:178432", "title": "Inhibition of rat liver RNA polymerases by action of the methylating agents dimethylnitrosamine in vivo and methyl methanesulfonate in vitro.", "content": "Dimethylnitrosamine maximally inhibits rat liver nuclear RNA synthesis by 50% at a dose of 40 mg/kg of body weight. The inhibition develops during the first 4 hr and persists through the 12th hr. All parenchymal cells of the lever lobule seem to be affected. The decreased RNA synthesis can be accounted for entirely by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified. A similar inhibition of the polymerase activities was demonstrated in the intact nuclei by inactivating the endogenous template with actinomycin D and assaying the polymerases with an added exogenous template, poly(deoxy-adenylate-deoxythymidylate). Chromatin was prepared by two methods differing in the extent to which they remove the endogenous polymerase activity. Each preparation was transcribed with either added Escherichia coli or partially purified rat liver nucleoplasmic RNA polymerase. With either polymerase or chromatin preparation, no inhibition of the template activity of liver nuclear chromatin isolated from the DMN-treated animals was detected. A similar mechanism of inhibition of RNA synthesis was produced by the action of the methylating agent methyl methanesulfonate on whole nuclei in vitro. The dose-dependent inhibition of RNA synthesis could be accounted for by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified from the affected nuclei. Chromatin prepared from the methyl methanesulfonate-treated nuclei had a normal template capacity with either E. coli or rat liver nucleoplasmic RNA polymerase. No preferential methylation of the RNA polymerases by [14C]methyl methanesulfonate could be demonstrated. It is concluded that the action of the two methylating agents on RNA metabolism is similar and that the inhibition of liver nuclear RNA synthesis results from inactivation of the RNA polymerases. At the same time, dimethylnitrosamine and methyl methanesulfonate leave the chromatin template intact, at least quantitatively, for the synthesis of RNA. The implications of such an effect on RNA synthesis are discussed.", "contents": "Inhibition of rat liver RNA polymerases by action of the methylating agents dimethylnitrosamine in vivo and methyl methanesulfonate in vitro. Dimethylnitrosamine maximally inhibits rat liver nuclear RNA synthesis by 50% at a dose of 40 mg/kg of body weight. The inhibition develops during the first 4 hr and persists through the 12th hr. All parenchymal cells of the lever lobule seem to be affected. The decreased RNA synthesis can be accounted for entirely by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified. A similar inhibition of the polymerase activities was demonstrated in the intact nuclei by inactivating the endogenous template with actinomycin D and assaying the polymerases with an added exogenous template, poly(deoxy-adenylate-deoxythymidylate). Chromatin was prepared by two methods differing in the extent to which they remove the endogenous polymerase activity. Each preparation was transcribed with either added Escherichia coli or partially purified rat liver nucleoplasmic RNA polymerase. With either polymerase or chromatin preparation, no inhibition of the template activity of liver nuclear chromatin isolated from the DMN-treated animals was detected. A similar mechanism of inhibition of RNA synthesis was produced by the action of the methylating agent methyl methanesulfonate on whole nuclei in vitro. The dose-dependent inhibition of RNA synthesis could be accounted for by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified from the affected nuclei. Chromatin prepared from the methyl methanesulfonate-treated nuclei had a normal template capacity with either E. coli or rat liver nucleoplasmic RNA polymerase. No preferential methylation of the RNA polymerases by [14C]methyl methanesulfonate could be demonstrated. It is concluded that the action of the two methylating agents on RNA metabolism is similar and that the inhibition of liver nuclear RNA synthesis results from inactivation of the RNA polymerases. At the same time, dimethylnitrosamine and methyl methanesulfonate leave the chromatin template intact, at least quantitatively, for the synthesis of RNA. The implications of such an effect on RNA synthesis are discussed."} {"id": "PMID:178433", "title": "Some effects of acute and chronic dosing with aflatoxin B1 on rat liver nuclei.", "content": "A study has been made of changes occurring in rat liver nuclei as a result of the chronic and acute administration of aflatoxin B1. This has involved resolution of the nuclei into populations of differing ploidy by means of centrifugation in a zonal rotor. Chronic feeding of the toxin to weanling rats prevents the development of the predominant tetraploid hepatocyte nuclear population, which normally takes place during maturation. Increased populations of diploid and octaploid hepatocyte nuclei are observed. Chronic feeding of the toxin to adult animals also causes a reduction in the tetraploid population already established and, again, leads to increased numbers of diploid and octaploid nuclei. Once an abnormal nuclear population has been established by feeding the toxin, it persists until the development of hepatocarcinoma (if a 6-week carcinogenic feeding regimen has been used). The hepatomas have diploid nuclei. Labeling hepatic RNA and DNA in vivo has indicated that feeding the toxin causes a reversion to the immature distribution of DNA synthesis among the nuclear population, with little effect on the pattern of distribution of RNA synthesis. Acute administration of aflatoxin to adult rats also causes a reduction in the size of the tetraploid population, with increased proportions of diploid, octaploid, and higherploidy nuclei. These results are discussed in terms of a dual action of the toxin, antimitotic and necrogenic, and the possible relationship of these to the carcinogenic process.", "contents": "Some effects of acute and chronic dosing with aflatoxin B1 on rat liver nuclei. A study has been made of changes occurring in rat liver nuclei as a result of the chronic and acute administration of aflatoxin B1. This has involved resolution of the nuclei into populations of differing ploidy by means of centrifugation in a zonal rotor. Chronic feeding of the toxin to weanling rats prevents the development of the predominant tetraploid hepatocyte nuclear population, which normally takes place during maturation. Increased populations of diploid and octaploid hepatocyte nuclei are observed. Chronic feeding of the toxin to adult animals also causes a reduction in the tetraploid population already established and, again, leads to increased numbers of diploid and octaploid nuclei. Once an abnormal nuclear population has been established by feeding the toxin, it persists until the development of hepatocarcinoma (if a 6-week carcinogenic feeding regimen has been used). The hepatomas have diploid nuclei. Labeling hepatic RNA and DNA in vivo has indicated that feeding the toxin causes a reversion to the immature distribution of DNA synthesis among the nuclear population, with little effect on the pattern of distribution of RNA synthesis. Acute administration of aflatoxin to adult rats also causes a reduction in the size of the tetraploid population, with increased proportions of diploid, octaploid, and higherploidy nuclei. These results are discussed in terms of a dual action of the toxin, antimitotic and necrogenic, and the possible relationship of these to the carcinogenic process."} {"id": "PMID:178434", "title": "Electron microscopic study of virus particles in yolk sac and placenta and in hematopoietic organs of newborn C3Hf mice.", "content": "Examination of yolk sac from a C3Hf and a C3H mouse with the electron microscope revealed the presence of C-type virus particles in the blood islands. Particles were observed budding from the plasma membrane of hemocytoblasts, from erythroblasts, and occasionally from reticulocytes. C-type particles were also found in similar cells in hematopoietic foci in the liver, spleen, and bone marrow of embryos, and they continued to be present in newborn C3Hf mice up to 11 days of age. Particles consistently appeared in the thymus, even in older suckling mice. A comparison is made between the presence of C-type particles in organs of embryonic, newborn, and adult C3Hf mice. C-type particles were not observed in the chorioallantoic placentas from mice that were given injections of mouse leukemia virus (Gross) or from normal noninjected mice; however, intracisternal A-type particles were present in cytotrophoblast cells from these placentas.", "contents": "Electron microscopic study of virus particles in yolk sac and placenta and in hematopoietic organs of newborn C3Hf mice. Examination of yolk sac from a C3Hf and a C3H mouse with the electron microscope revealed the presence of C-type virus particles in the blood islands. Particles were observed budding from the plasma membrane of hemocytoblasts, from erythroblasts, and occasionally from reticulocytes. C-type particles were also found in similar cells in hematopoietic foci in the liver, spleen, and bone marrow of embryos, and they continued to be present in newborn C3Hf mice up to 11 days of age. Particles consistently appeared in the thymus, even in older suckling mice. A comparison is made between the presence of C-type particles in organs of embryonic, newborn, and adult C3Hf mice. C-type particles were not observed in the chorioallantoic placentas from mice that were given injections of mouse leukemia virus (Gross) or from normal noninjected mice; however, intracisternal A-type particles were present in cytotrophoblast cells from these placentas."} {"id": "PMID:178435", "title": "Characteristics of progesterone-binding components in neoplastic mammary tissues of the rat.", "content": "Characteristics of [3H]progesterone-binding components were studied in cell-free preparations of two hormonally responsive tumors: the R3230AC mammary adenocarcinoma and 9,10-dimethyl-1,2-benzanthracene-induced mammary tumor of the rat. Progesterone-binding macromolecules from cytosols of both mammary neoplasms exhibited sedimentation coefficients of 3.5 to 4.0 S on sucrose gradients of either low or high ionic strength. From Scatchard analyses of titration data, apparent dissociation constants of 4 to 6 X 10(-8) M were determined for ligand-binding protein complexes from either tumor. Specific progesterone-binding capacities varied considerably, ranging from 150 to 650 fmoles/mg of cytosol protein. Optimal binding of [3H]progesterone was reached by 2 to 3 hr at 3 degrees, pH 7.4, and then decreased rapidly. Specificity studies indicated that cortisol, corticosterone, and triamcinolone acetonide competed effectively for [3H]progesterone-binding. This suggested that [3H] progesterone was bound largely to a macromolecule distinct from transcortin, which does not bind glucocorticoids containing 9alpha-fluoro groups. Aldosterone, as well as several androgens and estrogens, were weak competitors of binding except at high concentrations. The nature of the inhibition of progesterone-binding sites by triamcinolone acetonide and corticosterone was competitive. Concurrent titrations of [3H]progesterone and [3H]triamcinolone acetonide-binding sites demonstrated that their binding capacities were similar, considering the relative stabilities of the complexes. These results, which indicated that progesterone and glucocorticoids compete for the same binding site, suggest that these hormones may influence mammary gland differentiation and development by a common mechanism.", "contents": "Characteristics of progesterone-binding components in neoplastic mammary tissues of the rat. Characteristics of [3H]progesterone-binding components were studied in cell-free preparations of two hormonally responsive tumors: the R3230AC mammary adenocarcinoma and 9,10-dimethyl-1,2-benzanthracene-induced mammary tumor of the rat. Progesterone-binding macromolecules from cytosols of both mammary neoplasms exhibited sedimentation coefficients of 3.5 to 4.0 S on sucrose gradients of either low or high ionic strength. From Scatchard analyses of titration data, apparent dissociation constants of 4 to 6 X 10(-8) M were determined for ligand-binding protein complexes from either tumor. Specific progesterone-binding capacities varied considerably, ranging from 150 to 650 fmoles/mg of cytosol protein. Optimal binding of [3H]progesterone was reached by 2 to 3 hr at 3 degrees, pH 7.4, and then decreased rapidly. Specificity studies indicated that cortisol, corticosterone, and triamcinolone acetonide competed effectively for [3H]progesterone-binding. This suggested that [3H] progesterone was bound largely to a macromolecule distinct from transcortin, which does not bind glucocorticoids containing 9alpha-fluoro groups. Aldosterone, as well as several androgens and estrogens, were weak competitors of binding except at high concentrations. The nature of the inhibition of progesterone-binding sites by triamcinolone acetonide and corticosterone was competitive. Concurrent titrations of [3H]progesterone and [3H]triamcinolone acetonide-binding sites demonstrated that their binding capacities were similar, considering the relative stabilities of the complexes. These results, which indicated that progesterone and glucocorticoids compete for the same binding site, suggest that these hormones may influence mammary gland differentiation and development by a common mechanism."} {"id": "PMID:178436", "title": "Phase transition of plasma membranes of rat hepatocyte and hepatoma cells by electron diffraction.", "content": "The transition temperatures (Tc) of the plasma membranes of Reuber H-35 hepatoma and normal ACl rat hepatocytes were measured by electron diffraction under physiological conditions. Diffraction rings below Tc indicate the existence of solid lipid domains. The Tc of both membranes increase to a plateau value of 17.5 degrees during the storage period of 4 days at 4 degrees, the rate of increase being slower for normal liver membranes. The extrapolations to zero storage suggest an innate difference of Tc for these two membranes. Storage in oxygen-reduced media slows down the initial increase in Tc in normal liver membranes, while the depletion of divalent cations accelerates the increase. Differences in lipid composition are partly responsible for this behavior.", "contents": "Phase transition of plasma membranes of rat hepatocyte and hepatoma cells by electron diffraction. The transition temperatures (Tc) of the plasma membranes of Reuber H-35 hepatoma and normal ACl rat hepatocytes were measured by electron diffraction under physiological conditions. Diffraction rings below Tc indicate the existence of solid lipid domains. The Tc of both membranes increase to a plateau value of 17.5 degrees during the storage period of 4 days at 4 degrees, the rate of increase being slower for normal liver membranes. The extrapolations to zero storage suggest an innate difference of Tc for these two membranes. Storage in oxygen-reduced media slows down the initial increase in Tc in normal liver membranes, while the depletion of divalent cations accelerates the increase. Differences in lipid composition are partly responsible for this behavior."} {"id": "PMID:178437", "title": "Enhancement of tumor growth following immunization with Bacillus Calmette-Gu\u00e9rin cell walls.", "content": "The effect of preimmunization with Bacillus Calmette-Guerin cell walls (BCGcw) on tumor growth was studied with the use of transplantable Morris Hepatoma 3924a in inbred ACl rats. There was an increase in tumor incidence, an increase in the i.m. tumor growth rate, and an increase in the average i.m. tumor mass in animals that were preimmunized with BCGcw. The BCGcw-induced enhancement in tumor growth was dependent upon the amount of tumor present at the time of BCGcw immunization. No enhancement occurred in animals immunized with BCGcw 12 days after the inoculation of tumor cells.", "contents": "Enhancement of tumor growth following immunization with Bacillus Calmette-Gu\u00e9rin cell walls. The effect of preimmunization with Bacillus Calmette-Guerin cell walls (BCGcw) on tumor growth was studied with the use of transplantable Morris Hepatoma 3924a in inbred ACl rats. There was an increase in tumor incidence, an increase in the i.m. tumor growth rate, and an increase in the average i.m. tumor mass in animals that were preimmunized with BCGcw. The BCGcw-induced enhancement in tumor growth was dependent upon the amount of tumor present at the time of BCGcw immunization. No enhancement occurred in animals immunized with BCGcw 12 days after the inoculation of tumor cells."} {"id": "PMID:178438", "title": "The effect of substituents on the carcinogenicity of n-nitrosopyrrolidine in Sprague-Dawley rats.", "content": "N-Nitrosopyrrolidine and two of its derivatives were prepared and fed in drinking water to Sprague-Dawley rats to compare the effects of substituents on the carcinogenicity of the N-nitrosopyrrolidine molecule. 3,4-Dichloro-N-nitrosopyrrolidine induced esophageal tumors in 13 of 14 animals, olfactory carcinomas in 4, and a hepatocellular tumor in 1. All animals that received this compound were dead at 55 weeks after the start of the experiments. N-Nitrosopyrrolidine induced hepatocellular tumors in 26 of 29 animals and induced 1 olfactory carcinoma. Not all animals in this group were dead until 104 weeks of the experiment. 2,5-Dimethyl-N-nitrosopyrrolidine induced only 2 hepatocellular tumors in 29 animals. The alpha-methyl substitution diminished the liver carcinogenicity, while the beta chlorine substitution affected a different target organ, the esophagus, and greatly reduced the time to death with tumors.", "contents": "The effect of substituents on the carcinogenicity of n-nitrosopyrrolidine in Sprague-Dawley rats. N-Nitrosopyrrolidine and two of its derivatives were prepared and fed in drinking water to Sprague-Dawley rats to compare the effects of substituents on the carcinogenicity of the N-nitrosopyrrolidine molecule. 3,4-Dichloro-N-nitrosopyrrolidine induced esophageal tumors in 13 of 14 animals, olfactory carcinomas in 4, and a hepatocellular tumor in 1. All animals that received this compound were dead at 55 weeks after the start of the experiments. N-Nitrosopyrrolidine induced hepatocellular tumors in 26 of 29 animals and induced 1 olfactory carcinoma. Not all animals in this group were dead until 104 weeks of the experiment. 2,5-Dimethyl-N-nitrosopyrrolidine induced only 2 hepatocellular tumors in 29 animals. The alpha-methyl substitution diminished the liver carcinogenicity, while the beta chlorine substitution affected a different target organ, the esophagus, and greatly reduced the time to death with tumors."} {"id": "PMID:178439", "title": "Cyclic nucleotide phosphodiesterase activity in normal and neoplastic rat mammary cells grown in monolayer culture.", "content": "The activity of cyclic 3':5'-nucleotide phosphodiesterase (PDE) (EC 3.1.4.17) was measured in cultured normal and neoplastic rat mammary epithelium. Total PDE activity in normal cells was 1.6 to 6 times higher than that in tumor cells over a concentration range of 0.01 to 1 mM cyclic adenosine 3':5'-monophosphate. PDE activity was distributed between the low-speed (4000 x g) particulate and supernatant fractions in both cell lines, with the particulate fraction possessing 60 to 70% of the total. Double reciprocal kinetic plots were nonlinear, suggesting the presence of high- and low-affinity PDE activities. Similar, but not identical biphasic curves obtained from both normal and neoplastic cells suggested that at least two different PDE activities were present in a membrane-bound as well as a soluble form. Apparent Michealis constants for the high-affinity enzyme ranged from 2 to 6 muM; the low-affinity enzyme was 1 mM. In the presence of 10 mM caffeine and at a substrate concentration of 1 muM, PDE activity was inhibited 40 and 80% of basal levels in normal and tumor cells, respectively. In general, the membrane-bound enzyme was inhibited to a greater extent than the soluble, regardless of the cell line examined. Although normal cells exhibited higher PDE activities in terms of total specific activity, when soluble activities were compared at low substrate concentrations, the opposite was the case. At a substrate concentration of 0.01 muM, normal cell, low-Km soluble specific activity was 40% less than comparable tumor cell activity. Our results support the contention that PDE is induced by its own substrate, cyclic adenosine 3':5'-monophosphate. In addition, they suggest that the low cyclic adenosine 3':5'-monophosphate steady-state levels characteristic of malignant cells are maintained by a soluble high-affinity isozyme of PDE.", "contents": "Cyclic nucleotide phosphodiesterase activity in normal and neoplastic rat mammary cells grown in monolayer culture. The activity of cyclic 3':5'-nucleotide phosphodiesterase (PDE) (EC 3.1.4.17) was measured in cultured normal and neoplastic rat mammary epithelium. Total PDE activity in normal cells was 1.6 to 6 times higher than that in tumor cells over a concentration range of 0.01 to 1 mM cyclic adenosine 3':5'-monophosphate. PDE activity was distributed between the low-speed (4000 x g) particulate and supernatant fractions in both cell lines, with the particulate fraction possessing 60 to 70% of the total. Double reciprocal kinetic plots were nonlinear, suggesting the presence of high- and low-affinity PDE activities. Similar, but not identical biphasic curves obtained from both normal and neoplastic cells suggested that at least two different PDE activities were present in a membrane-bound as well as a soluble form. Apparent Michealis constants for the high-affinity enzyme ranged from 2 to 6 muM; the low-affinity enzyme was 1 mM. In the presence of 10 mM caffeine and at a substrate concentration of 1 muM, PDE activity was inhibited 40 and 80% of basal levels in normal and tumor cells, respectively. In general, the membrane-bound enzyme was inhibited to a greater extent than the soluble, regardless of the cell line examined. Although normal cells exhibited higher PDE activities in terms of total specific activity, when soluble activities were compared at low substrate concentrations, the opposite was the case. At a substrate concentration of 0.01 muM, normal cell, low-Km soluble specific activity was 40% less than comparable tumor cell activity. Our results support the contention that PDE is induced by its own substrate, cyclic adenosine 3':5'-monophosphate. In addition, they suggest that the low cyclic adenosine 3':5'-monophosphate steady-state levels characteristic of malignant cells are maintained by a soluble high-affinity isozyme of PDE."} {"id": "PMID:178440", "title": "Transfer RNA methylase activity and capacity during aflatoxin B1-induced hepatocellular carcinogenesis.", "content": "Transfer RNA methylase (tRNA methylase) activity and capacity were monitored in whole-rat-liver preparations during the induction of hepatocellular carcinomas by an 8-week aflatoxin B1 dosing regimen that produced minimal toxic effects. Significant phases of elevated tRNA methylase capacity occurred at 6 to 9 weeks (20%) and 24 to 29 weeks (40%). No significant change in tRNA methylase activity was noted over the course of the 55-week experiment. Higher aflatoxin B1 doses, producing acute toxic liver damage, resulted in elevated tRNA methylase activity (50%) and capacity (30%) at least as early as 1 week after dosing. Experiments with individual nodular lesions excised from livers of rats continuously fed a diet containing 2 ppm aflatoxin B1 demonstrated similarly elevated tRNA methylase activities and capacities in hyperplastic (preneoplastic)nodules, with and without histological evidence of carcinoma.", "contents": "Transfer RNA methylase activity and capacity during aflatoxin B1-induced hepatocellular carcinogenesis. Transfer RNA methylase (tRNA methylase) activity and capacity were monitored in whole-rat-liver preparations during the induction of hepatocellular carcinomas by an 8-week aflatoxin B1 dosing regimen that produced minimal toxic effects. Significant phases of elevated tRNA methylase capacity occurred at 6 to 9 weeks (20%) and 24 to 29 weeks (40%). No significant change in tRNA methylase activity was noted over the course of the 55-week experiment. Higher aflatoxin B1 doses, producing acute toxic liver damage, resulted in elevated tRNA methylase activity (50%) and capacity (30%) at least as early as 1 week after dosing. Experiments with individual nodular lesions excised from livers of rats continuously fed a diet containing 2 ppm aflatoxin B1 demonstrated similarly elevated tRNA methylase activities and capacities in hyperplastic (preneoplastic)nodules, with and without histological evidence of carcinoma."} {"id": "PMID:178441", "title": "A survey on the effect of steroid hormone on type C virus production from cultured murine cells.", "content": "Dexamethasone stimulates type C virus production induced by iododeoxyuridine (IdUrd) from several murine cell lines: uninfected BALB cells, virally transformed nonproducer K-BALB cells, mouse neuroblastoma N-4 cells, and rat tumor XC cells. Dexamethasone also stimulates virus production from BALB cells newly infected by some murine leukemia or leukemia sarcoma viruses, from a murine myelogenous leukemic cell line (M-1) producing type C virus, from K-BALB(l) cells (K-BALB producing cells previously induced by IdUrd), and from K-BALB cells rescued by Rauscher leukemia virus. However, this stimulatory effect is not universal, since we observed that dexamethasone did not stimulate virus production from BALB cells newly infected by B-tropic virus, from S2CL3 cells producing N-tropic virus (a clone of spontaneously transformed BALB cells), from virus producing normal rat kidney cells, and from a mouse adrenal gland tumor Y-1 cell line chronically producing type C virus. Some estrogenic hormones that do not have any stimulatory effect on virus production from BALB or K-BALB cells induced by IdUrd stimulate virus production from normal rat kidney cells induced by IdUrd. When there is no stimulation of virus production in a cell system by steroid hormones, very often there is some inhibitory activity. Furthermore, we observed that in JLSV10 cells chronically producing Rauscher leukemia virus and in K-BALB cells newly infected by Rauscher leukemia virus, virus production is enhanced by dexamethasone when the cells are still producing a low titer of virus but is not enhanced when the cells are producing a high titer of virus.", "contents": "A survey on the effect of steroid hormone on type C virus production from cultured murine cells. Dexamethasone stimulates type C virus production induced by iododeoxyuridine (IdUrd) from several murine cell lines: uninfected BALB cells, virally transformed nonproducer K-BALB cells, mouse neuroblastoma N-4 cells, and rat tumor XC cells. Dexamethasone also stimulates virus production from BALB cells newly infected by some murine leukemia or leukemia sarcoma viruses, from a murine myelogenous leukemic cell line (M-1) producing type C virus, from K-BALB(l) cells (K-BALB producing cells previously induced by IdUrd), and from K-BALB cells rescued by Rauscher leukemia virus. However, this stimulatory effect is not universal, since we observed that dexamethasone did not stimulate virus production from BALB cells newly infected by B-tropic virus, from S2CL3 cells producing N-tropic virus (a clone of spontaneously transformed BALB cells), from virus producing normal rat kidney cells, and from a mouse adrenal gland tumor Y-1 cell line chronically producing type C virus. Some estrogenic hormones that do not have any stimulatory effect on virus production from BALB or K-BALB cells induced by IdUrd stimulate virus production from normal rat kidney cells induced by IdUrd. When there is no stimulation of virus production in a cell system by steroid hormones, very often there is some inhibitory activity. Furthermore, we observed that in JLSV10 cells chronically producing Rauscher leukemia virus and in K-BALB cells newly infected by Rauscher leukemia virus, virus production is enhanced by dexamethasone when the cells are still producing a low titer of virus but is not enhanced when the cells are producing a high titer of virus."} {"id": "PMID:178442", "title": "Tumor-associated thymidine kinase in the sera of rats with transplanted hepatomas.", "content": "A cytoplasmic form of thymidine kinase was detected in sera from rats bearing Morris hepatoma 7777. Polyacrylamide electrophoretic properties demonstrate similarity between the serum enzyme extracted from hepatoma tissue. This form of thymidine kinase has also been described in normal human fetal tissue and a variety of human tumor cells. The results suggest that serum isoenzymes of thymidine kinase may be a useful adjunctive test for the presence of certain types of malignant tumors.", "contents": "Tumor-associated thymidine kinase in the sera of rats with transplanted hepatomas. A cytoplasmic form of thymidine kinase was detected in sera from rats bearing Morris hepatoma 7777. Polyacrylamide electrophoretic properties demonstrate similarity between the serum enzyme extracted from hepatoma tissue. This form of thymidine kinase has also been described in normal human fetal tissue and a variety of human tumor cells. The results suggest that serum isoenzymes of thymidine kinase may be a useful adjunctive test for the presence of certain types of malignant tumors."} {"id": "PMID:178443", "title": "Enhancement of infectivity and oncogenicity of a murine leukemia virus in adult mice by X-irradiation.", "content": "Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces thymic lymphomas histologically indistinguishable from those caused by neonatal infection. X-irradiation permitted early and high levels of viral expression when given before or after MuLV administration and hastened the development of lymphomas. Expression of virus was assayed by using a radioimmune assay for murine p30, a virion core protein. Seventeen to 21 days after injection of MuLV into adult mice, there was 0.3 mug p30 per ml serum, approximately 5 times normal. Seventeen to 21 days after injection of MuLV into X-irradiated (600R) adult mice, there were 2.7 mug p30 per ml serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice.", "contents": "Enhancement of infectivity and oncogenicity of a murine leukemia virus in adult mice by X-irradiation. Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces thymic lymphomas histologically indistinguishable from those caused by neonatal infection. X-irradiation permitted early and high levels of viral expression when given before or after MuLV administration and hastened the development of lymphomas. Expression of virus was assayed by using a radioimmune assay for murine p30, a virion core protein. Seventeen to 21 days after injection of MuLV into adult mice, there was 0.3 mug p30 per ml serum, approximately 5 times normal. Seventeen to 21 days after injection of MuLV into X-irradiated (600R) adult mice, there were 2.7 mug p30 per ml serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice."} {"id": "PMID:178445", "title": "Nucleotides in embryos in the stages of morula, gastrula, and neurula.", "content": "Levels of nucleotides and sugar nucleotides in embryos of Bufo arenarum at the stages of morula, gastrula, and neurula have been measured. The total amounts of purine nucleoside diphosphates decreased from morula to gastrula, but increased sharply from gastrula to neurula. The levels of ADP followed this pattern, but those of GDP did not change significantly through the three stages. Purine nucleoside triphosphate levels, which had increased immediately after fertilization, remained almost constant through morula, gastrula, and neurula. As with the purine nucleoside diphosphates, the adenine nucleotide decreased from morula to gastrula, and increased from gastrula to neurula. In contrast, the level of GTP showed a sharp maximum at gastrula. The total pyrimidine nucleoside triphosphate did not change significantly from morula through neurula. As in previous stages of development, only uridine sugar nucleotides were detected. A sharp increase of the galactosyl ester of nucleotides was found at gastrula.", "contents": "Nucleotides in embryos in the stages of morula, gastrula, and neurula. Levels of nucleotides and sugar nucleotides in embryos of Bufo arenarum at the stages of morula, gastrula, and neurula have been measured. The total amounts of purine nucleoside diphosphates decreased from morula to gastrula, but increased sharply from gastrula to neurula. The levels of ADP followed this pattern, but those of GDP did not change significantly through the three stages. Purine nucleoside triphosphate levels, which had increased immediately after fertilization, remained almost constant through morula, gastrula, and neurula. As with the purine nucleoside diphosphates, the adenine nucleotide decreased from morula to gastrula, and increased from gastrula to neurula. In contrast, the level of GTP showed a sharp maximum at gastrula. The total pyrimidine nucleoside triphosphate did not change significantly from morula through neurula. As in previous stages of development, only uridine sugar nucleotides were detected. A sharp increase of the galactosyl ester of nucleotides was found at gastrula."} {"id": "PMID:178446", "title": "Study on the proliferative state of haemopoietic stem cells (CFU).", "content": "Hydroxyurea was used to study the proliferation rate of haemopoietic stem cells (CFUs) in normal mice, after irradiation or transplantation into irradiated recipients. It was demonstrated that the proliferation rated of endogenous CFUs (endo-CFUs) and exogenous CFUs (exo-CFUs) are identical. After irradiation (650 R) the surviving endo-CFUs begin to proliferate immediately. By contrast exo-CFUs transplanted into the irradiated recipient mouse (850 R), begin to proliferate only after about 30 hr. However, injection of isoproterenol (which stimulates adenyl cyclase) or dibutyryl cyclic adenosin 3',5'-monophosphate shortly after marrow cell graft, triggers the transplanted CFUs into cell cycle as shown by an almost immediately increased sensitivity to hydroxyurea. Isoproterenol is capable of inducing DNA synthesis also in stem cells of normal mice but it takes about 20 hr before CFUs become to be increasingly sensitive to hydroxyurea.", "contents": "Study on the proliferative state of haemopoietic stem cells (CFU). Hydroxyurea was used to study the proliferation rate of haemopoietic stem cells (CFUs) in normal mice, after irradiation or transplantation into irradiated recipients. It was demonstrated that the proliferation rated of endogenous CFUs (endo-CFUs) and exogenous CFUs (exo-CFUs) are identical. After irradiation (650 R) the surviving endo-CFUs begin to proliferate immediately. By contrast exo-CFUs transplanted into the irradiated recipient mouse (850 R), begin to proliferate only after about 30 hr. However, injection of isoproterenol (which stimulates adenyl cyclase) or dibutyryl cyclic adenosin 3',5'-monophosphate shortly after marrow cell graft, triggers the transplanted CFUs into cell cycle as shown by an almost immediately increased sensitivity to hydroxyurea. Isoproterenol is capable of inducing DNA synthesis also in stem cells of normal mice but it takes about 20 hr before CFUs become to be increasingly sensitive to hydroxyurea."} {"id": "PMID:178447", "title": "Investigations on the turnover of adrenocortical mitochondria. IV. A stereological study of the effect of chronic treatment with ACTH on the size and number of rat zona reticularis mitochondria.", "content": "The effects of chronic administration of of ACTH (up to 36 consecutive days) on the mitochondria of the zona reticularis of the rat adrenal cortex were investigated by stereologic techniques. It was found that ACTH induces two phases of hypertrophy of mitochondria alternating with two proliferative stages, which are associated with a significant decrease in the average volume of the organelles. It is suggested that, as in the zona fasciculata, ACTH controls the processes of growth and division of mitochondria in the zona reticularis. The mechanism underlying this action of ACTH as well as the differences between the responses to ACTH of the mitochondrial population of the two adrenal zones are discussed in the light of evidence indicating that mitochondria contain a complete genetic apparatus largely independent of nuclear control.", "contents": "Investigations on the turnover of adrenocortical mitochondria. IV. A stereological study of the effect of chronic treatment with ACTH on the size and number of rat zona reticularis mitochondria. The effects of chronic administration of of ACTH (up to 36 consecutive days) on the mitochondria of the zona reticularis of the rat adrenal cortex were investigated by stereologic techniques. It was found that ACTH induces two phases of hypertrophy of mitochondria alternating with two proliferative stages, which are associated with a significant decrease in the average volume of the organelles. It is suggested that, as in the zona fasciculata, ACTH controls the processes of growth and division of mitochondria in the zona reticularis. The mechanism underlying this action of ACTH as well as the differences between the responses to ACTH of the mitochondrial population of the two adrenal zones are discussed in the light of evidence indicating that mitochondria contain a complete genetic apparatus largely independent of nuclear control."} {"id": "PMID:178448", "title": "Three muscle fibre types in the axial muscle of axolotl (Ambystoma mexicanum Shaw): a quantitative light- and electron microscopic study.", "content": "Morphometric analysis by light microscopy of p-phenylene-diamine stained semithin sections of axolotl tail muscle revealed differences in the cross-sectional area of the fibres and in the number of mitochondria and of lipid inclusions per fibre, and indicated the presence of three distinct types of fibres. The tripartition was found to be statistically highly significant. Representative fibres from each group established by light microscopic morphometry were subjected to an ultrastructural morphometric analysis. The volume content of mitochondria amounted to 9.8% of the fibre volume for red, 4.0% for intermediate and 0.8% for white fibres. The myofibrils composed 60%, 70% and 83% in the same fibres. The volume of the sarcotubular system (t-tubuli and sarcoplasmic reticulum) was 2.5% in red, 4.5% in intermediate and 11.7% in white fibres. The three fibre types also demonstrated differences in myofibrillar cross-striation pattern and number of triads. The reliability of the light microscopic morphometry was tested by correlation with EM montages of the representative fibres.", "contents": "Three muscle fibre types in the axial muscle of axolotl (Ambystoma mexicanum Shaw): a quantitative light- and electron microscopic study. Morphometric analysis by light microscopy of p-phenylene-diamine stained semithin sections of axolotl tail muscle revealed differences in the cross-sectional area of the fibres and in the number of mitochondria and of lipid inclusions per fibre, and indicated the presence of three distinct types of fibres. The tripartition was found to be statistically highly significant. Representative fibres from each group established by light microscopic morphometry were subjected to an ultrastructural morphometric analysis. The volume content of mitochondria amounted to 9.8% of the fibre volume for red, 4.0% for intermediate and 0.8% for white fibres. The myofibrils composed 60%, 70% and 83% in the same fibres. The volume of the sarcotubular system (t-tubuli and sarcoplasmic reticulum) was 2.5% in red, 4.5% in intermediate and 11.7% in white fibres. The three fibre types also demonstrated differences in myofibrillar cross-striation pattern and number of triads. The reliability of the light microscopic morphometry was tested by correlation with EM montages of the representative fibres."} {"id": "PMID:178449", "title": "A morphometric study on the pars intermedia of the hypophysis during impairment of the renin-angiotensin-aldosterone system in sodium depleted mice.", "content": "Fine structural alterations were investigated in cells of the pars intermedia of the pituitary of mice treated for four weeks with (a) a sodium deficient diet, (b) a sodium deficient diet mixed with propranolol (renin-inhibitor), (c) a sodium deficient diet combined with propranolol and amino-glutethimide (corticosterone 18-hydroxylase inhibitor), and (d) a sodium deficient diet combined with propranolol, aminoglutethimide and dexamethasone. The number of secretory granules decreased from 5.0/mum2 in the normal control of 2.4/mum2 in all four experimental groups suggesting that the cells in treated groups had reached an equilibrium in the production and release of secretory granules during the chronic treatments. The number of immature Golgi granules per unit Golgi area was 0.91 in the control, while this value rose to 3.29 (3.62 fold of the control), 4.37 (4.8 fold), 4.94 (5.43 fold) and 5.16 (5.67 fold) respectively in the four experimental groups. In these groups a good correlation was observed between the number of immature granules and the percent volume of rough endoplasmic reticulum (r=0.985, p less than 0.01). The present study suggests that the pars intermedia contains an unidentified pituitary factor (or factors) essential for aldosterone biosynthesis.", "contents": "A morphometric study on the pars intermedia of the hypophysis during impairment of the renin-angiotensin-aldosterone system in sodium depleted mice. Fine structural alterations were investigated in cells of the pars intermedia of the pituitary of mice treated for four weeks with (a) a sodium deficient diet, (b) a sodium deficient diet mixed with propranolol (renin-inhibitor), (c) a sodium deficient diet combined with propranolol and amino-glutethimide (corticosterone 18-hydroxylase inhibitor), and (d) a sodium deficient diet combined with propranolol, aminoglutethimide and dexamethasone. The number of secretory granules decreased from 5.0/mum2 in the normal control of 2.4/mum2 in all four experimental groups suggesting that the cells in treated groups had reached an equilibrium in the production and release of secretory granules during the chronic treatments. The number of immature Golgi granules per unit Golgi area was 0.91 in the control, while this value rose to 3.29 (3.62 fold of the control), 4.37 (4.8 fold), 4.94 (5.43 fold) and 5.16 (5.67 fold) respectively in the four experimental groups. In these groups a good correlation was observed between the number of immature granules and the percent volume of rough endoplasmic reticulum (r=0.985, p less than 0.01). The present study suggests that the pars intermedia contains an unidentified pituitary factor (or factors) essential for aldosterone biosynthesis."} {"id": "PMID:178450", "title": "Effects of chronic exercise on the ultrastructure of the adrenocortical cells in the rat.", "content": "Four groups of male rats were exercised for periods of 2, 4, 6, and 8 weeks with controls in each group. As a result of chronic exercise there was an increase in the width of the zona fasciculata of the adrenal cortex. Also, there was an increase in the number and size of the mitochondria, and an increase in the quantity of smooth endoplasmic reticulum, and during the first 4 weeks of exercise an increase in the number of lipid droplets in the zona fasciculata. The close relationship between the smooth endoplasmic reticulum and the mitochondria, and the relationship between the smooth endoplasmic reticulum and the lipid droplets suggests a possible means for a transport mechanism for movement of precursors between these organelles.", "contents": "Effects of chronic exercise on the ultrastructure of the adrenocortical cells in the rat. Four groups of male rats were exercised for periods of 2, 4, 6, and 8 weeks with controls in each group. As a result of chronic exercise there was an increase in the width of the zona fasciculata of the adrenal cortex. Also, there was an increase in the number and size of the mitochondria, and an increase in the quantity of smooth endoplasmic reticulum, and during the first 4 weeks of exercise an increase in the number of lipid droplets in the zona fasciculata. The close relationship between the smooth endoplasmic reticulum and the mitochondria, and the relationship between the smooth endoplasmic reticulum and the lipid droplets suggests a possible means for a transport mechanism for movement of precursors between these organelles."} {"id": "PMID:178453", "title": "Tissue distribution and mode of DNA methylation in mice by methyl methanesulphonate and N-methyl-N' -nitro-N-nitrosoguanidine: lack of thymic lymphoma induction and low extent of methylation of target tissue DNA at 0-6 of guanine.", "content": "The methylating agents methyl methanesulphonate (MMS) and N-methyl N'-nitro-N-nitrosoguanidine (MNNG), administered by single i.p. injection in mice failed to yield thymic lymphoma at doses around 60% of the LD50 values, in contrast to MNUA which gives a high yield of tumours by this route. Comparison of the tissue distribution and mode of DNA methylation by these agents showed a positive correlation with ability to methylate the 0-6 atom of guanine in DNA of the target tissues thymus and bone marrow and tumorigeneis. MMS gave a low yield of this product due to its relatively low Sn1 reactivity but was able to methylate DNA extensively at other sites in the target tissues and other organs examined. MNNG despite its ability to methylate 0-6 of guanine in DNA in vitro to the same relative extent as the potent carcinogen MNUA, methylated DNA of thymus and bone marrow to a very small extent in vivo but was able to methylate DNA in certain other tissues nearer the site of i.p. injection. These findings contrast with the general relatively extensive methylation of 0-6 of guanine in DNA of the target tissues and other organs by N-methyl-N-nitrosourea (MNUA).", "contents": "Tissue distribution and mode of DNA methylation in mice by methyl methanesulphonate and N-methyl-N' -nitro-N-nitrosoguanidine: lack of thymic lymphoma induction and low extent of methylation of target tissue DNA at 0-6 of guanine. The methylating agents methyl methanesulphonate (MMS) and N-methyl N'-nitro-N-nitrosoguanidine (MNNG), administered by single i.p. injection in mice failed to yield thymic lymphoma at doses around 60% of the LD50 values, in contrast to MNUA which gives a high yield of tumours by this route. Comparison of the tissue distribution and mode of DNA methylation by these agents showed a positive correlation with ability to methylate the 0-6 atom of guanine in DNA of the target tissues thymus and bone marrow and tumorigeneis. MMS gave a low yield of this product due to its relatively low Sn1 reactivity but was able to methylate DNA extensively at other sites in the target tissues and other organs examined. MNNG despite its ability to methylate 0-6 of guanine in DNA in vitro to the same relative extent as the potent carcinogen MNUA, methylated DNA of thymus and bone marrow to a very small extent in vivo but was able to methylate DNA in certain other tissues nearer the site of i.p. injection. These findings contrast with the general relatively extensive methylation of 0-6 of guanine in DNA of the target tissues and other organs by N-methyl-N-nitrosourea (MNUA)."} {"id": "PMID:178454", "title": "An assay for phosphotriester formation in the reaction of alkylating agents with deoxyribosenucleic acid in vitro and in vivo.", "content": "Preliminary studies in vitro using bacteriophage T7-DNA have shown that breaks formed in the DNA on the alkaline hydrolysis of apurinic sites and phosphotriesters can be distinguished from each other by measuring the extent of degradation of the DNA immediately after adding NaOH to 0.1 M and after incubating for 1 h in 0.5 M NaOH. This method has then been applied to the study of the formation and stability of phosphotriesters invivo. Methyl phosphotriesters formed in liver DNA following injection of mice with N-methyl-N-nitrosourea (MNUA) disappear with time (50% in 4-5 days). The concentration of ethyl phosphotriesters in liver DNA formed by injecting mice with N-ethyl-N-nitrosourea (ENUA) does not appear to decrease with time. Results of experiments on injecting methyl methane-sulphonate (MMS), ethyl methanesulphonate (EMS) and dimethyl sulphate (DMS) are also reported. The method described does not require the use of radioactively labelled reagents.", "contents": "An assay for phosphotriester formation in the reaction of alkylating agents with deoxyribosenucleic acid in vitro and in vivo. Preliminary studies in vitro using bacteriophage T7-DNA have shown that breaks formed in the DNA on the alkaline hydrolysis of apurinic sites and phosphotriesters can be distinguished from each other by measuring the extent of degradation of the DNA immediately after adding NaOH to 0.1 M and after incubating for 1 h in 0.5 M NaOH. This method has then been applied to the study of the formation and stability of phosphotriesters invivo. Methyl phosphotriesters formed in liver DNA following injection of mice with N-methyl-N-nitrosourea (MNUA) disappear with time (50% in 4-5 days). The concentration of ethyl phosphotriesters in liver DNA formed by injecting mice with N-ethyl-N-nitrosourea (ENUA) does not appear to decrease with time. Results of experiments on injecting methyl methane-sulphonate (MMS), ethyl methanesulphonate (EMS) and dimethyl sulphate (DMS) are also reported. The method described does not require the use of radioactively labelled reagents."} {"id": "PMID:178455", "title": "Mitochondrial functional changes during hepatic hyperplasia and azo dye carcinogenesis.", "content": "Resting and active-state respiratory velocities, respiratory control, high amplitude volume changes, and latent ATPase activities were examined in hepatic mitochondria from rats fed 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB) for production of liver tumors and from rats in three phases of liver regeneration subsequent to subtotal hepatectomies. Tetrabutylammonium bromide, a lipophilic probe capable of selectively inhibiting phosphorylating oxidation or uncoupling oxidation from phosphorylation, was used to detect subtle alterations in lipophilicity characteristics of the organelles and it was concluded that mitochondria from pre-hyperplastic, hyperplastic, and neoplastic tissues had a higher than normal degree of membrane lipophilicity at specific functional sites. Control of respiration by ADP was markedly augmented in all experimental groups; this behavior, plus depressed sensitivity to swelling agents and energized contraction, were similar in mitochondria from hepatomas and from 3-day regenerating livers. These mitochondrial functions were even more pronounced, however, in cells in pre-hyperplastic states (6 and 16 h subsequent to partial hepatectomy). Many forms of liver damage result in mitochondrial alterations which elevate the capacity for oxidative phosphorylation. Such changes associated with induction of azo dye oncogenesis are mimicked by the degree of hyperplasia in the tissue following the first mitotic wave of regeneration; implications relevant to hepatocarcinogenesis are discussed.", "contents": "Mitochondrial functional changes during hepatic hyperplasia and azo dye carcinogenesis. Resting and active-state respiratory velocities, respiratory control, high amplitude volume changes, and latent ATPase activities were examined in hepatic mitochondria from rats fed 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB) for production of liver tumors and from rats in three phases of liver regeneration subsequent to subtotal hepatectomies. Tetrabutylammonium bromide, a lipophilic probe capable of selectively inhibiting phosphorylating oxidation or uncoupling oxidation from phosphorylation, was used to detect subtle alterations in lipophilicity characteristics of the organelles and it was concluded that mitochondria from pre-hyperplastic, hyperplastic, and neoplastic tissues had a higher than normal degree of membrane lipophilicity at specific functional sites. Control of respiration by ADP was markedly augmented in all experimental groups; this behavior, plus depressed sensitivity to swelling agents and energized contraction, were similar in mitochondria from hepatomas and from 3-day regenerating livers. These mitochondrial functions were even more pronounced, however, in cells in pre-hyperplastic states (6 and 16 h subsequent to partial hepatectomy). Many forms of liver damage result in mitochondrial alterations which elevate the capacity for oxidative phosphorylation. Such changes associated with induction of azo dye oncogenesis are mimicked by the degree of hyperplasia in the tissue following the first mitotic wave of regeneration; implications relevant to hepatocarcinogenesis are discussed."} {"id": "PMID:178456", "title": "A versatile, flexible synthesis of 1,3-diglycerides and tryglycerides.", "content": "A flexible method for synthesising 1,30diflycerides and triglycerides is described. Glycidol esters, prepared by a known route from epichlorohydrin and the sodium salt of a fatty acid, were heated with another or with the same fatty acid and a quaternary ammonium salt. This resulted in a fast, mild reaction and higher yields and greater purity of the diglycerides than hitherto obtained in this synthesis. The mixture of 1,3- and 1,2-diglycerides obtained was isomerised by heating while still in the solid phase to 1,3-diglycerides. Triglycerides were prepared from the diglycerides by acylation using a fatty acid chloride and pyridine in hexane.", "contents": "A versatile, flexible synthesis of 1,3-diglycerides and tryglycerides. A flexible method for synthesising 1,30diflycerides and triglycerides is described. Glycidol esters, prepared by a known route from epichlorohydrin and the sodium salt of a fatty acid, were heated with another or with the same fatty acid and a quaternary ammonium salt. This resulted in a fast, mild reaction and higher yields and greater purity of the diglycerides than hitherto obtained in this synthesis. The mixture of 1,3- and 1,2-diglycerides obtained was isomerised by heating while still in the solid phase to 1,3-diglycerides. Triglycerides were prepared from the diglycerides by acylation using a fatty acid chloride and pyridine in hexane."} {"id": "PMID:178458", "title": "[Immunologic blood-brain barrier in the polyoma virus--Syrian hamster system].", "content": "The authors report premilinary results of an experiment on permeability of the blood-brain barrier (BBB) to anti-tumor virus-induced immunological factors in the polyoma virus/Syrian Hamster system. The animals were protected by subcutaneous or intracranial injections with virus before challenge with polyoma virus transformed cells by both routes. BBB seemed to be permeable to the efferent part of the subcutaneously induced immune reaction. On the contrary, antigenic information introduced in the central nervous system was trapped inside the BBB. Thus the BBB might offer a \"one-way\" permeability in this system.", "contents": "[Immunologic blood-brain barrier in the polyoma virus--Syrian hamster system]. The authors report premilinary results of an experiment on permeability of the blood-brain barrier (BBB) to anti-tumor virus-induced immunological factors in the polyoma virus/Syrian Hamster system. The animals were protected by subcutaneous or intracranial injections with virus before challenge with polyoma virus transformed cells by both routes. BBB seemed to be permeable to the efferent part of the subcutaneously induced immune reaction. On the contrary, antigenic information introduced in the central nervous system was trapped inside the BBB. Thus the BBB might offer a \"one-way\" permeability in this system."} {"id": "PMID:178459", "title": "Control of protein balance in hypertrophied cardiac muscle.", "content": "The levels of intracellular proteins are determined by a balance between their rates of synthesis and degradation. During the development of regression of cardiac hypertrophy, both of these rates can be expected to change. Possible control sites of synthetic and degradation processes are discussed in this article. The following experimental results are presented: (1) Cardiac mitochondrial cytochromes accumulate early after imposition of pressure overload, as a result of an increased rate of synthesis and decreased rate of degradation. (2) The half-life of myosin heavy chains (HC) in the steady state was determined from incorporation kinetics, using leucyl-tRNA as precursor, to be 5-6 days. (3) The existence of a pool of newly synthesized myofilaments which are not fully incorporated into the core of myofibrils is indicated by the incorporation data.", "contents": "Control of protein balance in hypertrophied cardiac muscle. The levels of intracellular proteins are determined by a balance between their rates of synthesis and degradation. During the development of regression of cardiac hypertrophy, both of these rates can be expected to change. Possible control sites of synthetic and degradation processes are discussed in this article. The following experimental results are presented: (1) Cardiac mitochondrial cytochromes accumulate early after imposition of pressure overload, as a result of an increased rate of synthesis and decreased rate of degradation. (2) The half-life of myosin heavy chains (HC) in the steady state was determined from incorporation kinetics, using leucyl-tRNA as precursor, to be 5-6 days. (3) The existence of a pool of newly synthesized myofilaments which are not fully incorporated into the core of myofibrils is indicated by the incorporation data."} {"id": "PMID:178460", "title": "Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria.", "content": "The responses of cardiac mitochondria to anoxia may be evaluated in terms of the oxidation-reduction state of the electron carriers and the ability of the mitochondria to function in energy-linked reactions. The previous detailed evaluation of the oxygen requirements for electron transfer in mitochondria is here extended to the oxygen requirements for energy-linked functions. Four functions are evaluated: the energy-dependent reduction of pyridine nucleotide, the phosphorylation of ADP, the retention of Ca2+, and the establishment of a membrane potential. All of these functions are half-maximally activated with 10-20% oxidation of cytochromes c and a + a3. Fifty percent oxidation of pyridine nucleotide is required for these functions. In a normoxic-anoxic titration, an increment of 50% in the reduction of pyridine nucleotide in intact tissue corresponds to the point at which the mitochondria are half-maximally active in energy coupling. Thus, the use of pyridine nucleotide fluorescence as an optimal indicator of tissue oxidation-reduction states has now been extended to the assay of energy-linked functions of mitochondria in situ in cardiac tissue.", "contents": "Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria. The responses of cardiac mitochondria to anoxia may be evaluated in terms of the oxidation-reduction state of the electron carriers and the ability of the mitochondria to function in energy-linked reactions. The previous detailed evaluation of the oxygen requirements for electron transfer in mitochondria is here extended to the oxygen requirements for energy-linked functions. Four functions are evaluated: the energy-dependent reduction of pyridine nucleotide, the phosphorylation of ADP, the retention of Ca2+, and the establishment of a membrane potential. All of these functions are half-maximally activated with 10-20% oxidation of cytochromes c and a + a3. Fifty percent oxidation of pyridine nucleotide is required for these functions. In a normoxic-anoxic titration, an increment of 50% in the reduction of pyridine nucleotide in intact tissue corresponds to the point at which the mitochondria are half-maximally active in energy coupling. Thus, the use of pyridine nucleotide fluorescence as an optimal indicator of tissue oxidation-reduction states has now been extended to the assay of energy-linked functions of mitochondria in situ in cardiac tissue."} {"id": "PMID:178461", "title": "Enhanced aldosterone response to angiotensin II in human hypertension.", "content": "Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A II was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A II at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 +/- 0.6 ng/dl) was significantly less (P less than 0.001) than that in patients with essential hypertension (19 +/- 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P less than 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity.", "contents": "Enhanced aldosterone response to angiotensin II in human hypertension. Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A II was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A II at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 +/- 0.6 ng/dl) was significantly less (P less than 0.001) than that in patients with essential hypertension (19 +/- 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P less than 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity."} {"id": "PMID:178462", "title": "Receptor binding of angiotensin II and antagonists. Correlation with aldosterone production by isolated canine adrenal glomerulosa cells.", "content": "The binding properties of the angiotensin II receptors of the adrenal cortex have been studied in isolated cells prepared by collagenase dispersion of the zona glomerulosa of the canine adrenal gland. Such cell preparations are responsive to physiological concentrations of angiotensin II, and permit correlation of binding of angiotensin II and its analogues with aldosterone production in vitro. Uptake of 125I-angiotensin II (5 X 10(-11) M) by glomerulosa cells at 37 degrees C reached a steady state at 45 minutes, with a subsequent plateau for at least 60 minutes. Angiotensin II binding was also dependent upon the hormone and cell concentrations employed during uptake studies. Bound angiotensin II was rapidly dissociated from canine adrenal cells after addition of the unlabeled octapeptide. High affinity sites with equilibrium association constant (Ka) of 3.3 X 10(9) M-1 comprised 25-33% of the receptor population and the remainder of the sites were of lower affinity, 2.5 X 10(8)M-1. Binding of angiotensin II analogues and antagonists was found to be consistent with their biological activities. The analogue most extensively evaluated was [Sar-1]angiotensin II, which exhibited enhanced binding activity when compared to angiotensin II, and had a higher equilibrium association constant by kinetic analysis and direct binding studies. Direct binding of labeled angiotensin II to the adrenal glomerulosa receptor has been correlated with a progressive response in aldosterone production. The steroidogenic response to angiotensin II was maximal when 25% of the receptor population was occupied; this fraction corresponds to the proportion of high affinity receptor sites measured by binding analysis. In addition, inhibition of angiotensin II binding to receptor sites by the competitive antagonist [Sar-1, Ala-8]angiotensin II has been correlated with inhibition of aldosterone production. These findings serve to demonstrate the biological significance of the angiotensin II binding sites of the adrenal cortex, and confirm their role as receptors which mediate the steroidogenic responses to angiotensin II.", "contents": "Receptor binding of angiotensin II and antagonists. Correlation with aldosterone production by isolated canine adrenal glomerulosa cells. The binding properties of the angiotensin II receptors of the adrenal cortex have been studied in isolated cells prepared by collagenase dispersion of the zona glomerulosa of the canine adrenal gland. Such cell preparations are responsive to physiological concentrations of angiotensin II, and permit correlation of binding of angiotensin II and its analogues with aldosterone production in vitro. Uptake of 125I-angiotensin II (5 X 10(-11) M) by glomerulosa cells at 37 degrees C reached a steady state at 45 minutes, with a subsequent plateau for at least 60 minutes. Angiotensin II binding was also dependent upon the hormone and cell concentrations employed during uptake studies. Bound angiotensin II was rapidly dissociated from canine adrenal cells after addition of the unlabeled octapeptide. High affinity sites with equilibrium association constant (Ka) of 3.3 X 10(9) M-1 comprised 25-33% of the receptor population and the remainder of the sites were of lower affinity, 2.5 X 10(8)M-1. Binding of angiotensin II analogues and antagonists was found to be consistent with their biological activities. The analogue most extensively evaluated was [Sar-1]angiotensin II, which exhibited enhanced binding activity when compared to angiotensin II, and had a higher equilibrium association constant by kinetic analysis and direct binding studies. Direct binding of labeled angiotensin II to the adrenal glomerulosa receptor has been correlated with a progressive response in aldosterone production. The steroidogenic response to angiotensin II was maximal when 25% of the receptor population was occupied; this fraction corresponds to the proportion of high affinity receptor sites measured by binding analysis. In addition, inhibition of angiotensin II binding to receptor sites by the competitive antagonist [Sar-1, Ala-8]angiotensin II has been correlated with inhibition of aldosterone production. These findings serve to demonstrate the biological significance of the angiotensin II binding sites of the adrenal cortex, and confirm their role as receptors which mediate the steroidogenic responses to angiotensin II."} {"id": "PMID:178463", "title": "The effects of des-Asp1-angiotensin II on blood pressure, plasma aldosterone concentration, and plasma renin activity in the rabbit.", "content": "To examine the hypothesis that des-Asp-1-angiotensin II (angiotensin III) may be an important mediator of various responses to angiotensin II, both peptides were given sequentially at 25 ng/kg per min by systemic infusion to conscious rabbits, and the effects on blood pressure, plasma aldosterone concentration, and plasma renin activity were compared. The mean arterial pressure increased with angiotensin II infusion an average of 18.2 mm Hg, and with angiotensin III infusion only 3.2 mm Hg. Both peptides, however, produced a six- to sevenfold increase in plasma aldosterone concentration, and a threefold decrease in plasma renin activity. Renal clearance data suggest that the suppression of renin activity was not a consequence of renal hemodynamic change or altered sodium transport, but of direct inhibition through a receptor mediating a short feedback loop. These data in the intact rabbit, taken together with in vitro studies by others, suggest that the responses of these three organ systems to angiotensin peptides are mediated by receptors of varied specificity: those mediating vasoconstriction exhibit a greater response to angiotensin II than to angiotensin III; those mediating the secretion of aldosterone exhibit a lesser response to angiotensin II than to angiotensin III; and those mediating the suppression of renin release do not appear to discriminate between the two peptides.", "contents": "The effects of des-Asp1-angiotensin II on blood pressure, plasma aldosterone concentration, and plasma renin activity in the rabbit. To examine the hypothesis that des-Asp-1-angiotensin II (angiotensin III) may be an important mediator of various responses to angiotensin II, both peptides were given sequentially at 25 ng/kg per min by systemic infusion to conscious rabbits, and the effects on blood pressure, plasma aldosterone concentration, and plasma renin activity were compared. The mean arterial pressure increased with angiotensin II infusion an average of 18.2 mm Hg, and with angiotensin III infusion only 3.2 mm Hg. Both peptides, however, produced a six- to sevenfold increase in plasma aldosterone concentration, and a threefold decrease in plasma renin activity. Renal clearance data suggest that the suppression of renin activity was not a consequence of renal hemodynamic change or altered sodium transport, but of direct inhibition through a receptor mediating a short feedback loop. These data in the intact rabbit, taken together with in vitro studies by others, suggest that the responses of these three organ systems to angiotensin peptides are mediated by receptors of varied specificity: those mediating vasoconstriction exhibit a greater response to angiotensin II than to angiotensin III; those mediating the secretion of aldosterone exhibit a lesser response to angiotensin II than to angiotensin III; and those mediating the suppression of renin release do not appear to discriminate between the two peptides."} {"id": "PMID:178464", "title": "Changes in cardiovascular and adrenal cortical responses to angiotensin III induced by sodium deprivation in the rat.", "content": "The restriction of dietary sodium intake is known to depress the cardiovascular responses to angiotensin II and increase the sensitivity of the adrenal zona glomerulosa to this steroidogenic octapeptide. In sodium-repleted animals, angiotensin III is a weak pressor substance and a potent stimulant of aldosterone biosynthesis. The effect of a low sodium diet on vascular and steroidogenic responses to angiotensin II and angiotensin III was investigated. In nephrectomized rats, angiotensin III had one-third of the pressor activity relative to angiotensin II when either normal or sodium-deprived animals were compared. When administered subcutaneously (sc) to rats, angiotensin II and III induced comparable steroidogenic responses, whereas only angiotensin II significantly elevated blood pressure. The comparison of cell suspensions from control adrenals with suspensions of adrenals from sodium-deprived animals showed that the zona glomerulosa from rats on low sodium diets had increased wet weight (20%), cell protein (25%), and basal steroidogenic rats (45%). Adrenocorticotropic hormone (ACTH)-induced responses in adrenal cells from low sodium animals were about twice the responses of cells from normal adrenals. Angiotensin II and III stimulated the cortex at a threshold concentration of 5 X 10(-10) M and induced a maximum response at about 5 X 10(-8) M in cells prepared from normal rat adrenals. In cells dispersed from adrenal capsules of sodium-deprived rats, the maximal steroidogenic response to angiotensin II occurred at 3 X 10(-8) M, whereas angiotensin III was maximal at 1 X 10(-9) M. Aldosterone synthesis induced by both peptides was increased approximately 45% in adrenal cells from low salt rats. At 0.9 mumol/kg, sc, Sar-1, Ile-8-angiotensin II antagonized cardiovascular responses to angiotensin II and did not alter aldosterone in the sodium-deprived rat. In contrast, treatment with Ile-7-angiotensin III blocked the adrenal cortex but not the vascular actions of angiotensin II. These data are consistent with a role for angiotensin III in the renin-angiotensin-aldosterone response to sodium deprivation.", "contents": "Changes in cardiovascular and adrenal cortical responses to angiotensin III induced by sodium deprivation in the rat. The restriction of dietary sodium intake is known to depress the cardiovascular responses to angiotensin II and increase the sensitivity of the adrenal zona glomerulosa to this steroidogenic octapeptide. In sodium-repleted animals, angiotensin III is a weak pressor substance and a potent stimulant of aldosterone biosynthesis. The effect of a low sodium diet on vascular and steroidogenic responses to angiotensin II and angiotensin III was investigated. In nephrectomized rats, angiotensin III had one-third of the pressor activity relative to angiotensin II when either normal or sodium-deprived animals were compared. When administered subcutaneously (sc) to rats, angiotensin II and III induced comparable steroidogenic responses, whereas only angiotensin II significantly elevated blood pressure. The comparison of cell suspensions from control adrenals with suspensions of adrenals from sodium-deprived animals showed that the zona glomerulosa from rats on low sodium diets had increased wet weight (20%), cell protein (25%), and basal steroidogenic rats (45%). Adrenocorticotropic hormone (ACTH)-induced responses in adrenal cells from low sodium animals were about twice the responses of cells from normal adrenals. Angiotensin II and III stimulated the cortex at a threshold concentration of 5 X 10(-10) M and induced a maximum response at about 5 X 10(-8) M in cells prepared from normal rat adrenals. In cells dispersed from adrenal capsules of sodium-deprived rats, the maximal steroidogenic response to angiotensin II occurred at 3 X 10(-8) M, whereas angiotensin III was maximal at 1 X 10(-9) M. Aldosterone synthesis induced by both peptides was increased approximately 45% in adrenal cells from low salt rats. At 0.9 mumol/kg, sc, Sar-1, Ile-8-angiotensin II antagonized cardiovascular responses to angiotensin II and did not alter aldosterone in the sodium-deprived rat. In contrast, treatment with Ile-7-angiotensin III blocked the adrenal cortex but not the vascular actions of angiotensin II. These data are consistent with a role for angiotensin III in the renin-angiotensin-aldosterone response to sodium deprivation."} {"id": "PMID:178466", "title": "Sympathetic nerve activity: role in regulation of blood pressure in the spontaenously hypertensive rat.", "content": "Sympathetic nerve activity (SNA) and high pressure baroreceptor regulation of SNA were studied in the Okamoto strain of spontaneously hypertensive rat (SHR). Mean arterial pressure (MAP) and SNA were not significantly affected by anesthesia with low doses of pentobarbital (20-25 mg/kg). Thus, most of these studies were performed in anesthetized rats. SNA in visceral sympathetic nerves increased rapidly with age up to 24 weeks and slowly thereafter. MAP increased with SNA, following the same time course. Both SNA and MAP in SHR were significantly greater than that found in normotensive Wistar control rats of comparable ages. Abolition of ganglionic transmission with hexamethonium in both SHR and normotensive controls reduced postganglionic SNA and MAP to comparable levels. In SHR less than 16 weeks old, increased baroreceptor stimulation effectively inhibited SNA with the same sensitivity as found in Wistar control rats. However, older SHR appeared to lose their ability to completely inhibit SNA during induced hypertension, whereas in Wistar control rats as old as 52 weeks, elevation of blood pressure to 165.3 +/- 2.3 mm Hg completely suppressed SNA. These results suggest that SNA may play an important role in the development and maintenance of hypertension in SHR, and that central sympathetic centers, uninhibited by baroreceptor afferents, become active during the development of hypertension in the SHR.", "contents": "Sympathetic nerve activity: role in regulation of blood pressure in the spontaenously hypertensive rat. Sympathetic nerve activity (SNA) and high pressure baroreceptor regulation of SNA were studied in the Okamoto strain of spontaneously hypertensive rat (SHR). Mean arterial pressure (MAP) and SNA were not significantly affected by anesthesia with low doses of pentobarbital (20-25 mg/kg). Thus, most of these studies were performed in anesthetized rats. SNA in visceral sympathetic nerves increased rapidly with age up to 24 weeks and slowly thereafter. MAP increased with SNA, following the same time course. Both SNA and MAP in SHR were significantly greater than that found in normotensive Wistar control rats of comparable ages. Abolition of ganglionic transmission with hexamethonium in both SHR and normotensive controls reduced postganglionic SNA and MAP to comparable levels. In SHR less than 16 weeks old, increased baroreceptor stimulation effectively inhibited SNA with the same sensitivity as found in Wistar control rats. However, older SHR appeared to lose their ability to completely inhibit SNA during induced hypertension, whereas in Wistar control rats as old as 52 weeks, elevation of blood pressure to 165.3 +/- 2.3 mm Hg completely suppressed SNA. These results suggest that SNA may play an important role in the development and maintenance of hypertension in SHR, and that central sympathetic centers, uninhibited by baroreceptor afferents, become active during the development of hypertension in the SHR."} {"id": "PMID:178467", "title": "Plasma cyclic adenosine 3':5'-monophosphate response to isoproterenol and glucagon in hyperkinetic borderline (labile) hypertension.", "content": "The hemodynamic changes observed in patients with the \"hyperkinetic\" form of borderline (labile) essential hypertension (BEH) could be related to the hyperresponsiveness of cardiac beta-adrenergic receptors to catecholamines. The isoproterenol-induced increase in plasma cyclic adenosine 3':5'-monophosphate (cAMP) reflects the response of adenylate cyclase to beta-adrenergic stimulation, whereas a non-beta-receptor-mediated increase occurs with the administration of glucagon. Both substances were infused into 13 control subjects and 14 patients with the hyperkinetic form of BEH before and after propranolol administration. Baseline plasma cAMP concentrations were comparable in both groups. After 30 minutes of isoproterenol infusion (20 ng/kg per min) a significantly higher increase in plasma cAMP and heart rate and a smaller decrease in diastolic blood pressure were seen in this type of BEH than in control subjects. The increase in plasma cAMP and in heart rate correlated positively when all subjects were considered together. Propranolol abolished hemodynamic and humoral responses to a similar degree in both groups. The plasma cAMP responses to glucagon (200 ng/kg per min) were slightly lower in our patients with BEH than in control subjects and were not suppressed by propranolol. The data are compatible with a hyperreactivity of the beta-adrenergic receptors or of the adenylate cyclase or both in hyperkinetic BEH and could correspond to the previously observed exaggerated beta-adrenergic drive to the heart in this type of hypertension. The non-beta-receptor-mediated rise in plasma cAMP (glucagon), however, remains comparable in control subjects and BEH.", "contents": "Plasma cyclic adenosine 3':5'-monophosphate response to isoproterenol and glucagon in hyperkinetic borderline (labile) hypertension. The hemodynamic changes observed in patients with the \"hyperkinetic\" form of borderline (labile) essential hypertension (BEH) could be related to the hyperresponsiveness of cardiac beta-adrenergic receptors to catecholamines. The isoproterenol-induced increase in plasma cyclic adenosine 3':5'-monophosphate (cAMP) reflects the response of adenylate cyclase to beta-adrenergic stimulation, whereas a non-beta-receptor-mediated increase occurs with the administration of glucagon. Both substances were infused into 13 control subjects and 14 patients with the hyperkinetic form of BEH before and after propranolol administration. Baseline plasma cAMP concentrations were comparable in both groups. After 30 minutes of isoproterenol infusion (20 ng/kg per min) a significantly higher increase in plasma cAMP and heart rate and a smaller decrease in diastolic blood pressure were seen in this type of BEH than in control subjects. The increase in plasma cAMP and in heart rate correlated positively when all subjects were considered together. Propranolol abolished hemodynamic and humoral responses to a similar degree in both groups. The plasma cAMP responses to glucagon (200 ng/kg per min) were slightly lower in our patients with BEH than in control subjects and were not suppressed by propranolol. The data are compatible with a hyperreactivity of the beta-adrenergic receptors or of the adenylate cyclase or both in hyperkinetic BEH and could correspond to the previously observed exaggerated beta-adrenergic drive to the heart in this type of hypertension. The non-beta-receptor-mediated rise in plasma cAMP (glucagon), however, remains comparable in control subjects and BEH."} {"id": "PMID:178468", "title": "Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response.", "content": "Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors.", "contents": "Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response. Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors."} {"id": "PMID:178469", "title": "Studies on the serum lipoprotein composition in 50-year-old men. A suggestion of chemical criteria for diagnosis of hyperlipoproteinaemia type III (Broad-beta disease).", "content": "The serum lipoprotein (LP) composition in hyperlipoproteinaemia (HLP) type III, when studied in a population of 50-year-old men, was characterized by a high cholesterol/triglyceride ratio in the very low density lipoprotien (VLDL) fraction, a high low density lipoprotein (LDL) triglyceride concentration and a low LDL cholesterol/triglyceride ratio. No one of these three variables, however, was found to be a suitable single parameter for diagnosis for HLP type III because of an overlap between HLP type III and other LP patterns with regard to the studied variables. In an effort to find a parameter with a better discriminative capacity a \"III-index\" was invented.", "contents": "Studies on the serum lipoprotein composition in 50-year-old men. A suggestion of chemical criteria for diagnosis of hyperlipoproteinaemia type III (Broad-beta disease). The serum lipoprotein (LP) composition in hyperlipoproteinaemia (HLP) type III, when studied in a population of 50-year-old men, was characterized by a high cholesterol/triglyceride ratio in the very low density lipoprotien (VLDL) fraction, a high low density lipoprotein (LDL) triglyceride concentration and a low LDL cholesterol/triglyceride ratio. No one of these three variables, however, was found to be a suitable single parameter for diagnosis for HLP type III because of an overlap between HLP type III and other LP patterns with regard to the studied variables. In an effort to find a parameter with a better discriminative capacity a \"III-index\" was invented."} {"id": "PMID:178470", "title": "Effects of growth hormone release-inhibiting hormone and bromocryptine (CB 154) in states of abnormal pituitary-adrenal function.", "content": "Growth hormone release-inhibiting hormone (GHR-IH) was administered to five patients with abnormal pituitary-adrenal function. There was immediate suppression by about 50% of ACTH levels in two patients who had undergone bilateral adrenalectomy because of Cushing's disease; one of them had Nelson's syndrome. Bromocryptine (2-5 mg) suppressed ACTH levels by 62-67% for more than 6 h in these patients. GHR-IH did not significantly influence cortisol secretion by an adrenal carcinoma and only slight changes were seen in two patients with Addison's disease. The possible therapeutic implications are discussed.", "contents": "Effects of growth hormone release-inhibiting hormone and bromocryptine (CB 154) in states of abnormal pituitary-adrenal function. Growth hormone release-inhibiting hormone (GHR-IH) was administered to five patients with abnormal pituitary-adrenal function. There was immediate suppression by about 50% of ACTH levels in two patients who had undergone bilateral adrenalectomy because of Cushing's disease; one of them had Nelson's syndrome. Bromocryptine (2-5 mg) suppressed ACTH levels by 62-67% for more than 6 h in these patients. GHR-IH did not significantly influence cortisol secretion by an adrenal carcinoma and only slight changes were seen in two patients with Addison's disease. The possible therapeutic implications are discussed."} {"id": "PMID:178472", "title": "Circulating antibody to renal collecting ducts in patients with hepatoma or renal-cell carcinoma.", "content": "An anti-kidney antibody was demonstrated by the indirect immunofluorescence method in the serum of patients with primary tumours of the liver or kidney. The distribution of fluorescence in rabbit kidney was consistent with that of antibody to collecting ducts. The anti-collecting duct antibody (anti-CDA) could be absorbed from serum by normal adult rabbit or human kidney tissue and by one of three specimens of renal-cell carcinoma tissue. Anti-CDA differed from anti-mitochondrial antibodies and from anti-liver/kidney microsomal antibody in the pattern of fluorescent staining obtained with rabbit kidney. Two-hundred sera from patients with cancer and other diseases and forty-three from healthy hospital personnel were tested for anti-CDA. Eleven of the twenty-five positive sera were from patients with primary cancer of the liver or urinary tract, and all but six of the remainder were from patients with tumours involving the liver or with liver disorders that may be associated with nodular hyperplasia or tumour.", "contents": "Circulating antibody to renal collecting ducts in patients with hepatoma or renal-cell carcinoma. An anti-kidney antibody was demonstrated by the indirect immunofluorescence method in the serum of patients with primary tumours of the liver or kidney. The distribution of fluorescence in rabbit kidney was consistent with that of antibody to collecting ducts. The anti-collecting duct antibody (anti-CDA) could be absorbed from serum by normal adult rabbit or human kidney tissue and by one of three specimens of renal-cell carcinoma tissue. Anti-CDA differed from anti-mitochondrial antibodies and from anti-liver/kidney microsomal antibody in the pattern of fluorescent staining obtained with rabbit kidney. Two-hundred sera from patients with cancer and other diseases and forty-three from healthy hospital personnel were tested for anti-CDA. Eleven of the twenty-five positive sera were from patients with primary cancer of the liver or urinary tract, and all but six of the remainder were from patients with tumours involving the liver or with liver disorders that may be associated with nodular hyperplasia or tumour."} {"id": "PMID:178473", "title": "Cell-mediated immunity to microbial antigens in mother and child.", "content": "We have looked at evidence for the transplacental passage of cell-mediated immunity in man. The lymphocyte response of mother-neonate pairs was assessed to non-specific mitogens, allogeneic cells, and to microbial antigens. Although six mothers were known to be chronic carriers of Herpes simplex virus only one of their neonates responded to this viral antigen. On two occasions a lymphocyte response was induced in cord blood by antigens to which the mother did not respond. This paradox remains unexplained. We suggest that the relative immunity of the neonate to some infectious diseases does not depend on the transplacental passage of cellular immunity.", "contents": "Cell-mediated immunity to microbial antigens in mother and child. We have looked at evidence for the transplacental passage of cell-mediated immunity in man. The lymphocyte response of mother-neonate pairs was assessed to non-specific mitogens, allogeneic cells, and to microbial antigens. Although six mothers were known to be chronic carriers of Herpes simplex virus only one of their neonates responded to this viral antigen. On two occasions a lymphocyte response was induced in cord blood by antigens to which the mother did not respond. This paradox remains unexplained. We suggest that the relative immunity of the neonate to some infectious diseases does not depend on the transplacental passage of cellular immunity."} {"id": "PMID:178474", "title": "Evidence for suppressor cell activity associated with induction of Herpesvirus saimiri-induced lymphoma.", "content": "Peripheral blood lymphocytes (PBL) from Herpesvirus saimiri (HVS) infected owl monkeys lose their ability to respond to PHA during the development of lymphoma. In this study, five HVS-infected owl monkeys were examined for their ability to respond to PHA and to confer this loss of PHA reactivity to normal lymphocytes. Four of the monkeys developed HVS-induced disease and lost their ability to respond to PHA. Although less affected, reduced responses were also found with PWM. The animals which developed disease and suppressed PHA responses were found to be able to confer this loss of PHA reactivity to normal lymphocytes. One HVS-infected monkey did not develop disease or loss of PHA reactivity and did not confer a loss of PHA reactivity to normal lymphocytes. In the four affected monkeys, the conference of suppression to PHA was not accompanied by a concomitant reduction in response to PWM by the normal lymphocytes, demonstrating some specificity in the suppressor cell activity. Thus, the presence of suppressor cell activity appears to be associated with the inhibition of T-cell function and possibly the eventual development of lymphoma.", "contents": "Evidence for suppressor cell activity associated with induction of Herpesvirus saimiri-induced lymphoma. Peripheral blood lymphocytes (PBL) from Herpesvirus saimiri (HVS) infected owl monkeys lose their ability to respond to PHA during the development of lymphoma. In this study, five HVS-infected owl monkeys were examined for their ability to respond to PHA and to confer this loss of PHA reactivity to normal lymphocytes. Four of the monkeys developed HVS-induced disease and lost their ability to respond to PHA. Although less affected, reduced responses were also found with PWM. The animals which developed disease and suppressed PHA responses were found to be able to confer this loss of PHA reactivity to normal lymphocytes. One HVS-infected monkey did not develop disease or loss of PHA reactivity and did not confer a loss of PHA reactivity to normal lymphocytes. In the four affected monkeys, the conference of suppression to PHA was not accompanied by a concomitant reduction in response to PWM by the normal lymphocytes, demonstrating some specificity in the suppressor cell activity. Thus, the presence of suppressor cell activity appears to be associated with the inhibition of T-cell function and possibly the eventual development of lymphoma."} {"id": "PMID:178475", "title": "Effects of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns.", "content": "Marijuana extract, given in daily doses containing 70 to 210 mg delta-9-tetrahydrocannabinol (THC), induced effects on sleep that were virtually identical to those produced by the same doses of relatively pure (96%) THC. Both drugs reduced eye movements density with some tolerance developing to this effect. Stage 4 tendend to increase with drug administration. Abrupt withdrawal led to extremely high densities of eye movement, increased rapid eye movement (REM) durations, and a sharp but transient fall in stage 4 to baseline levels. These effects may be useful in the elucidation of the pharmacology of sleep. The effects on sleep of THC administration (but not withdrawal) closely resemble those induced by lithium. For this reason, we suggest further studies of THC in affective disorders. Evidence available thus far suggests that THC produces dysphoric symptoms in unipolar but not in bipolar depressed patients; these differences in response may prove of diagnostic value. An adequate therapeutic trial of THC in bipolar depressed patients has not yet been carried out.", "contents": "Effects of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns. Marijuana extract, given in daily doses containing 70 to 210 mg delta-9-tetrahydrocannabinol (THC), induced effects on sleep that were virtually identical to those produced by the same doses of relatively pure (96%) THC. Both drugs reduced eye movements density with some tolerance developing to this effect. Stage 4 tendend to increase with drug administration. Abrupt withdrawal led to extremely high densities of eye movement, increased rapid eye movement (REM) durations, and a sharp but transient fall in stage 4 to baseline levels. These effects may be useful in the elucidation of the pharmacology of sleep. The effects on sleep of THC administration (but not withdrawal) closely resemble those induced by lithium. For this reason, we suggest further studies of THC in affective disorders. Evidence available thus far suggests that THC produces dysphoric symptoms in unipolar but not in bipolar depressed patients; these differences in response may prove of diagnostic value. An adequate therapeutic trial of THC in bipolar depressed patients has not yet been carried out."} {"id": "PMID:178478", "title": "Hydroxyproline-containing structural glycopeptide fractions from subacute inflammation connective tissue.", "content": "Hydroxyproline-containing structural glycopeptide fractions were isolated from collagenase-digested neutral salt-insoluble collagen of five-day sponge-implant connective tissue of the rat. The glycopeptide fractions characterized migrate as a single, strongly anionic band on disc gel electrophoresis at pH 9.5, are eluted on gel filtration as a small molecular weight peak, approximately 2000, and are resolved into thirteen glycopeptide fractions by DEAE-cellulose chromatography. Amino acid analyses of some of these fractions indicate a similarity in composition, the principal ones being aspartic and glutamic acids, serine, glycine, alanine, valine, proline and hydroxyproline. Three neutral carbohydrates, glucose, mannose and xylose, in different relative proportions and hexosamine are also present in the fractions. Amino-terminal amino acid determinations indicate a microheterogeneity of the glycopeptides. The electrophoretic behaviour and non-diffusibility of the small molecular weight glycopeptides suggest an intimate association between acidic hydroxyproline-containing peptides and carbohydrate components of developing connective tissue.", "contents": "Hydroxyproline-containing structural glycopeptide fractions from subacute inflammation connective tissue. Hydroxyproline-containing structural glycopeptide fractions were isolated from collagenase-digested neutral salt-insoluble collagen of five-day sponge-implant connective tissue of the rat. The glycopeptide fractions characterized migrate as a single, strongly anionic band on disc gel electrophoresis at pH 9.5, are eluted on gel filtration as a small molecular weight peak, approximately 2000, and are resolved into thirteen glycopeptide fractions by DEAE-cellulose chromatography. Amino acid analyses of some of these fractions indicate a similarity in composition, the principal ones being aspartic and glutamic acids, serine, glycine, alanine, valine, proline and hydroxyproline. Three neutral carbohydrates, glucose, mannose and xylose, in different relative proportions and hexosamine are also present in the fractions. Amino-terminal amino acid determinations indicate a microheterogeneity of the glycopeptides. The electrophoretic behaviour and non-diffusibility of the small molecular weight glycopeptides suggest an intimate association between acidic hydroxyproline-containing peptides and carbohydrate components of developing connective tissue."} {"id": "PMID:178482", "title": "Diffuse interstitial fibrosing pneumonitis and adenovirus infection.", "content": "With electron microscopy, adenovirus particles, which were almost round, variable in density, and 60-80 mmu in diameter, were observed in the nuclei of type II alveolar epithelial cells, infiltrated plasma cells and alveolar macrophages of a man with chronic interstitial fibrosing pneumonitis. The immunofluorescent technique also suggested adenovirus infection.", "contents": "Diffuse interstitial fibrosing pneumonitis and adenovirus infection. With electron microscopy, adenovirus particles, which were almost round, variable in density, and 60-80 mmu in diameter, were observed in the nuclei of type II alveolar epithelial cells, infiltrated plasma cells and alveolar macrophages of a man with chronic interstitial fibrosing pneumonitis. The immunofluorescent technique also suggested adenovirus infection."} {"id": "PMID:178484", "title": "Effect of antibiotics on the phagocytosis and killing of Pseudomonas aeruginosa by rabbit polymorphonuclear leukocytes.", "content": "The effect of antibiotics on phagocytosis and killing of Pseudomonas aeruginosa by rabbit polymorphonuclear leukocytes was studied. Carbenicillin and sulbenicillin, when added to an incubation medium at a concentration as low as 1/16 MIC, increased phagocytosis and killing of P. aeruginosa by PMN. Meanwhile, gentamicin and 3',4'-dideoxykanamycin B gave no influence on the PMN activity, and polymyxin B and colistin enhanced the activity only at MIC. The PMN activity was not facilitated even when the cells of P. aeruginosa had been pretreated with antibiotics. The bactericidal activity of PMN decreased after sonification, but was restored following addition of carbenicillin.", "contents": "Effect of antibiotics on the phagocytosis and killing of Pseudomonas aeruginosa by rabbit polymorphonuclear leukocytes. The effect of antibiotics on phagocytosis and killing of Pseudomonas aeruginosa by rabbit polymorphonuclear leukocytes was studied. Carbenicillin and sulbenicillin, when added to an incubation medium at a concentration as low as 1/16 MIC, increased phagocytosis and killing of P. aeruginosa by PMN. Meanwhile, gentamicin and 3',4'-dideoxykanamycin B gave no influence on the PMN activity, and polymyxin B and colistin enhanced the activity only at MIC. The PMN activity was not facilitated even when the cells of P. aeruginosa had been pretreated with antibiotics. The bactericidal activity of PMN decreased after sonification, but was restored following addition of carbenicillin."} {"id": "PMID:178485", "title": "Growth inhibition of cells in cultures and of vaccinia virus infected HeLa cells by derivatives of trifluorothymidine.", "content": "The effects of 5-trifluoromethyluracil (F3Thy), 5-trifluoromethyl-2'-deoxyuridine (F3dThd), F3dThd-5'-P, and F3dThd-5'-methylphosphonate on the growth of HeLa cells, Novikoff hepatoma cells, L5178Y mouse leukemia cells, and on the replication of vaccinia virus in HeLa cells have been determined. F3Thy and F3dThd-5'-methylophosphonate were approximately 500-fold and 100-fold less effective, respectively, than F3dThd or F3dThd-5'-P in their inhibition of these cells. F3dThd and F3dThd-5'-P are potent inhibitors of vaccinia viral replication of HeLa cells. The nucleoside and nucleotide were 1,000-fold more inhibitory than the free base. F3dThd was nost inhibitory when added between 1 and 2 h post-infection; however, it was also somewhat inhibitory when added at later times.", "contents": "Growth inhibition of cells in cultures and of vaccinia virus infected HeLa cells by derivatives of trifluorothymidine. The effects of 5-trifluoromethyluracil (F3Thy), 5-trifluoromethyl-2'-deoxyuridine (F3dThd), F3dThd-5'-P, and F3dThd-5'-methylphosphonate on the growth of HeLa cells, Novikoff hepatoma cells, L5178Y mouse leukemia cells, and on the replication of vaccinia virus in HeLa cells have been determined. F3Thy and F3dThd-5'-methylophosphonate were approximately 500-fold and 100-fold less effective, respectively, than F3dThd or F3dThd-5'-P in their inhibition of these cells. F3dThd and F3dThd-5'-P are potent inhibitors of vaccinia viral replication of HeLa cells. The nucleoside and nucleotide were 1,000-fold more inhibitory than the free base. F3dThd was nost inhibitory when added between 1 and 2 h post-infection; however, it was also somewhat inhibitory when added at later times."} {"id": "PMID:178486", "title": "Chromosome-associated paracrystalline nuclear inclusions in the spermatocytes of a pulmonate snail, Planorbarius corneus L.", "content": "Chromosome-associated paracrystalloids are regularly found in the spermatocytes of snails which were reared in the laboratory. They seem to be largely specific for the male gametocytes as they have been observed only in few cases in the oocytes. It is likely that paracrystalloids are formed during pachytene at the site of large heterochromatic knobs which originate by fusion of heterochromatic terminal segments of some bivalents. During diplotene they are always connected with the telomeres of three or four bivalents, thus forming a large trefoil-like structure. During metaphase I paracrystalloids are shed off from the chromosomes and transferred to the cytoplasm. In early spermatids they are found again in the nuclei, where they \"fade away\" during spermiogenesis. Histochemically they consist of basic proteins, which are probably crystallized in the cubic system. Radioactive labeling of the structure could not be achieved, neither by 3H-uridine or thymidine, nor by amino acids. The functional significance of this peculiar structure in unknown. Certain features justify a comparison with synaptonemal polycomplexes.", "contents": "Chromosome-associated paracrystalline nuclear inclusions in the spermatocytes of a pulmonate snail, Planorbarius corneus L. Chromosome-associated paracrystalloids are regularly found in the spermatocytes of snails which were reared in the laboratory. They seem to be largely specific for the male gametocytes as they have been observed only in few cases in the oocytes. It is likely that paracrystalloids are formed during pachytene at the site of large heterochromatic knobs which originate by fusion of heterochromatic terminal segments of some bivalents. During diplotene they are always connected with the telomeres of three or four bivalents, thus forming a large trefoil-like structure. During metaphase I paracrystalloids are shed off from the chromosomes and transferred to the cytoplasm. In early spermatids they are found again in the nuclei, where they \"fade away\" during spermiogenesis. Histochemically they consist of basic proteins, which are probably crystallized in the cubic system. Radioactive labeling of the structure could not be achieved, neither by 3H-uridine or thymidine, nor by amino acids. The functional significance of this peculiar structure in unknown. Certain features justify a comparison with synaptonemal polycomplexes."} {"id": "PMID:178496", "title": "[Estimation of free cortisol in urine (author's transl)].", "content": "Radio-immunological estimation of free cortisol in urine in a group of normal persons showed a median daily excretion of 42,5 +/- 22,8 mug (n = 31) using radio-loss-labelling, extraction, and thin layer chromatography. After simple extraction the median value was 54.1 +/- 15.3 mug/d (n = 10). Radioimmunological estimation in simple urine extract seems to be sufficient for routine clinical purposes. The estimation of free cortisol in urine permits a better differentiation between normal adrenal function and adrenal hyperactivity than the determination of 17-hydroxycorticosteroids (17-OHCS). This is shown by comparison of 1) the frequency distribution of the basal values of 17-OHCS and free cortisol in normal persons and in Cushing's disease, 2) the suppression effect of dexamethasone on 17-OHCS and free cortisol in Cushing patients, and 3) the stimulatory effect of ACTH on 17-OHCS and free cortisol in normal persons.", "contents": "[Estimation of free cortisol in urine (author's transl)]. Radio-immunological estimation of free cortisol in urine in a group of normal persons showed a median daily excretion of 42,5 +/- 22,8 mug (n = 31) using radio-loss-labelling, extraction, and thin layer chromatography. After simple extraction the median value was 54.1 +/- 15.3 mug/d (n = 10). Radioimmunological estimation in simple urine extract seems to be sufficient for routine clinical purposes. The estimation of free cortisol in urine permits a better differentiation between normal adrenal function and adrenal hyperactivity than the determination of 17-hydroxycorticosteroids (17-OHCS). This is shown by comparison of 1) the frequency distribution of the basal values of 17-OHCS and free cortisol in normal persons and in Cushing's disease, 2) the suppression effect of dexamethasone on 17-OHCS and free cortisol in Cushing patients, and 3) the stimulatory effect of ACTH on 17-OHCS and free cortisol in normal persons."} {"id": "PMID:178497", "title": "Production of oestradiol, camp and 125I-hcg binding by rat ovaries during the reproductive cycle.", "content": "Plasma concentration of oestradiol in female rats is dynamically altered in the reproductive cycle, depending on the biosynthesis and secretion of oestradiol secretion by the ovaries. The present study has followed oestradiol and cAMP concentration in the plasma and ovaries, and 125I-HCG binding during the pro-oestrus, oestrus and di-oestrus. Oestradiol concentration in plasma and its production by the ovaries were found to be highest in the pro-oestrus and lowest in the oestrus. These changes depend on the production and secretion of gonadotrophins. The mediator of gonadotropin action is cAMP whose ovarian concentration is lowest in the oestrus. LH stimulates the cAMP synthesis in the ovaries during the cyclic stages, without any significant difference being apparent between the various stages. 125I-HCG binding is highest in the di-oestrus stage, when concentration of endogenous gonadotrophins is low.", "contents": "Production of oestradiol, camp and 125I-hcg binding by rat ovaries during the reproductive cycle. Plasma concentration of oestradiol in female rats is dynamically altered in the reproductive cycle, depending on the biosynthesis and secretion of oestradiol secretion by the ovaries. The present study has followed oestradiol and cAMP concentration in the plasma and ovaries, and 125I-HCG binding during the pro-oestrus, oestrus and di-oestrus. Oestradiol concentration in plasma and its production by the ovaries were found to be highest in the pro-oestrus and lowest in the oestrus. These changes depend on the production and secretion of gonadotrophins. The mediator of gonadotropin action is cAMP whose ovarian concentration is lowest in the oestrus. LH stimulates the cAMP synthesis in the ovaries during the cyclic stages, without any significant difference being apparent between the various stages. 125I-HCG binding is highest in the di-oestrus stage, when concentration of endogenous gonadotrophins is low."} {"id": "PMID:178498", "title": "A modification of the Detter and Klingm\u00fcller's method for urinary alpha- and beta-pregnanediol and pregnanetriol determination: excretion patterns in men and in women during the normal menstrual cycle.", "content": "This report describes the modification of Detter and Klingm\u00fcller's method for the determination of urinary alpha- and beta-pregnanediol and pregnanetriol by means of thin -layer chromatography. The modifications were as follows: 1. The addition of formol prior to hydrolysis to prevent pigments penetration into urinary extracts. 2. The use of Kieselgel HF 254+366 nach Stahl (E. Merck, Darmstadt) which allows to localize the spots under UV-light at 366 nm without the use of colour reagents. The results concerning accuracy, sensitivity, precision and specificity in the modification described are profitable. Using this method in 7 healthy women (aged 28-37) with normal menstrual cycles the urinary excretion of alpha- and beta-pregnanediol and pregnanetriol were evaluated every second day (starting the 6th day of the cycle). The maximum of excretion of alpha- and beta-pregnandiol appeared on day 20 of the cycle, with the mean (+/- S.D.) 1.27 +/- 0.37 mg/24hr and 2.97 +/- 0.80 mg/24hr for alpha- and beta-pregnanediol, respectively. Mean values of pregnantriol were at the same level and ranged from 0.25 to 1.42 mg/24 hr. Single determination of these compounds in 8 healthy men (aged 19-42) revealed the mean excretion values (+/- S.D.) 0.96 +/- 0.17 mg/24 hr, 1.24 +/- 0.40 mg/24 hr, 1.12 +/- 0.65 mg/24 hr for alpha- and beta-pregnanediol and pregnanetriol, respectively.", "contents": "A modification of the Detter and Klingm\u00fcller's method for urinary alpha- and beta-pregnanediol and pregnanetriol determination: excretion patterns in men and in women during the normal menstrual cycle. This report describes the modification of Detter and Klingm\u00fcller's method for the determination of urinary alpha- and beta-pregnanediol and pregnanetriol by means of thin -layer chromatography. The modifications were as follows: 1. The addition of formol prior to hydrolysis to prevent pigments penetration into urinary extracts. 2. The use of Kieselgel HF 254+366 nach Stahl (E. Merck, Darmstadt) which allows to localize the spots under UV-light at 366 nm without the use of colour reagents. The results concerning accuracy, sensitivity, precision and specificity in the modification described are profitable. Using this method in 7 healthy women (aged 28-37) with normal menstrual cycles the urinary excretion of alpha- and beta-pregnanediol and pregnanetriol were evaluated every second day (starting the 6th day of the cycle). The maximum of excretion of alpha- and beta-pregnandiol appeared on day 20 of the cycle, with the mean (+/- S.D.) 1.27 +/- 0.37 mg/24hr and 2.97 +/- 0.80 mg/24hr for alpha- and beta-pregnanediol, respectively. Mean values of pregnantriol were at the same level and ranged from 0.25 to 1.42 mg/24 hr. Single determination of these compounds in 8 healthy men (aged 19-42) revealed the mean excretion values (+/- S.D.) 0.96 +/- 0.17 mg/24 hr, 1.24 +/- 0.40 mg/24 hr, 1.12 +/- 0.65 mg/24 hr for alpha- and beta-pregnanediol and pregnanetriol, respectively."} {"id": "PMID:178499", "title": "ACTH and growth hormone relationship in fetal rat adrenal steroidogenesis in vitro.", "content": "The effects of growth hormone and ACTH, alone or in combination, on fetal rat adrenal steroidogenesis in vitro were examined on the last day of intrauterine development. ACTH increased, while growth hormone did not affect fetal adrenal weight. ACTH increased fetal rat adrenal steroidogenesis, hydroxylation of 4-14C-progesterone to corticosterone, 18-hydroxy-11-deoxycorticosterone, 11-hydroxycorticosterone and aldosterone. Growth hormone alone had no effect on fetal adrenal steroidogenesis. ACTH and growth hormone administered together increased the conversion of progesterone to the above mentioned steroids to a greater extent than ACTH alone. The results indicate that growth hormone may participate in the fetal rat adrenal steroidogenesis potentiating the effects of fetal pituitary ACTH.", "contents": "ACTH and growth hormone relationship in fetal rat adrenal steroidogenesis in vitro. The effects of growth hormone and ACTH, alone or in combination, on fetal rat adrenal steroidogenesis in vitro were examined on the last day of intrauterine development. ACTH increased, while growth hormone did not affect fetal adrenal weight. ACTH increased fetal rat adrenal steroidogenesis, hydroxylation of 4-14C-progesterone to corticosterone, 18-hydroxy-11-deoxycorticosterone, 11-hydroxycorticosterone and aldosterone. Growth hormone alone had no effect on fetal adrenal steroidogenesis. ACTH and growth hormone administered together increased the conversion of progesterone to the above mentioned steroids to a greater extent than ACTH alone. The results indicate that growth hormone may participate in the fetal rat adrenal steroidogenesis potentiating the effects of fetal pituitary ACTH."} {"id": "PMID:178500", "title": "The fate of serotonin released from the intrathyroidal mast cells in albino rat.", "content": "After the administration of 500 muC of 3H-5-HT the mast cells were degranulated by 1500 IU of PO B. The grains were found within the follicular cells and in the vicinity and wall of the arterioles. These findings support both the direct and indirect (vascular) mechanism of action exerted by serotonin on the thyroid function.", "contents": "The fate of serotonin released from the intrathyroidal mast cells in albino rat. After the administration of 500 muC of 3H-5-HT the mast cells were degranulated by 1500 IU of PO B. The grains were found within the follicular cells and in the vicinity and wall of the arterioles. These findings support both the direct and indirect (vascular) mechanism of action exerted by serotonin on the thyroid function."} {"id": "PMID:178501", "title": "Investigations on isolated islets of Langerhans in vitro. XIII. Experiments concerning the preparation conditions with collagenase.", "content": "During the digestion of pancreatic pieces with collagenase for prepartion of isolated islets the enzymes in incubation medium (collangenolytic and/or proteolytic) can alter the secretion behavior of A- and B-cells. Insulin release after such an enzymatic attack is characterized by an enhanced basal secretion and a diminished and delayed glucose response. Overdigestion results in a decreased glucagon secretion in response to arginine, a diminished insulin content, and a decreased thiol-protein-disulfide-oxidoreductase activity of the islets. Increased albumin concentrations did not prevent the collagenase effect.", "contents": "Investigations on isolated islets of Langerhans in vitro. XIII. Experiments concerning the preparation conditions with collagenase. During the digestion of pancreatic pieces with collagenase for prepartion of isolated islets the enzymes in incubation medium (collangenolytic and/or proteolytic) can alter the secretion behavior of A- and B-cells. Insulin release after such an enzymatic attack is characterized by an enhanced basal secretion and a diminished and delayed glucose response. Overdigestion results in a decreased glucagon secretion in response to arginine, a diminished insulin content, and a decreased thiol-protein-disulfide-oxidoreductase activity of the islets. Increased albumin concentrations did not prevent the collagenase effect."} {"id": "PMID:178521", "title": "Effects of starvation and Ca++ on glucose-induced accumulation of cyclic 3',5'-AMP in pancreatic islets.", "content": "Exposure to glucose in the presence of 3-isobutyl-1-methylxanthine leads to accumulation of cAMP in islets microdissected from ob/ob mice. This process is dependent on extracellular Ca++ but differs markedly from the glucose action on insulin release in the same in vitro system in disappearing after 18 h of starvation.", "contents": "Effects of starvation and Ca++ on glucose-induced accumulation of cyclic 3',5'-AMP in pancreatic islets. Exposure to glucose in the presence of 3-isobutyl-1-methylxanthine leads to accumulation of cAMP in islets microdissected from ob/ob mice. This process is dependent on extracellular Ca++ but differs markedly from the glucose action on insulin release in the same in vitro system in disappearing after 18 h of starvation."} {"id": "PMID:178522", "title": "Adenyl cyclase activity of mouse liver membranes after incubation with endotoxin and epinephrine.", "content": "Adenyl cyclase activity in isolated mouse liver cell membranes was stimulated two-fold by endotoxin. Furthermore, endotoxin inhibited epinephrine induction of adenyl cyclase activity, apparently through interruption of the phospholipid moiety of the enzyme complex.", "contents": "Adenyl cyclase activity of mouse liver membranes after incubation with endotoxin and epinephrine. Adenyl cyclase activity in isolated mouse liver cell membranes was stimulated two-fold by endotoxin. Furthermore, endotoxin inhibited epinephrine induction of adenyl cyclase activity, apparently through interruption of the phospholipid moiety of the enzyme complex."} {"id": "PMID:178523", "title": "Reinterpretation of the ultrastructure of cartilage matrix.", "content": "The epiphyseal cartilage from new-born mouse was treated with collagenase in two ways: either before fixation or after glutaraldehyde fixation. The electron dense granules of the matrix were not seen in the micrographs of cartilage treated with collagenase before fixation. It is concluded that collagen plays a definite role in the formation of the granules at the time of tissue fixation and that the granules are fixation artifacts.", "contents": "Reinterpretation of the ultrastructure of cartilage matrix. The epiphyseal cartilage from new-born mouse was treated with collagenase in two ways: either before fixation or after glutaraldehyde fixation. The electron dense granules of the matrix were not seen in the micrographs of cartilage treated with collagenase before fixation. It is concluded that collagen plays a definite role in the formation of the granules at the time of tissue fixation and that the granules are fixation artifacts."} {"id": "PMID:178524", "title": "Effect of ACTH on the zona reticularis of the rat adrenal cortex: an ultrastructural stereologic study.", "content": "The effects of ACTH on the rat adrenal zona reticularis were investigated by stereologic methods. It was found that the zona reticularis cell responsiveness to ACTH is similar to that of the zona fasciculata elements. This excludes that the zona reticularis of the adult rat can only function as the site of destruction of worn-out elements migrating from the adrenal outer zones.", "contents": "Effect of ACTH on the zona reticularis of the rat adrenal cortex: an ultrastructural stereologic study. The effects of ACTH on the rat adrenal zona reticularis were investigated by stereologic methods. It was found that the zona reticularis cell responsiveness to ACTH is similar to that of the zona fasciculata elements. This excludes that the zona reticularis of the adult rat can only function as the site of destruction of worn-out elements migrating from the adrenal outer zones."} {"id": "PMID:178525", "title": "Monolayer cultures of normal adult rat adrenocortical cells: steroidogenic responses to nucleotides, bacterial toxins and antimicrotubular agents.", "content": "Monolayer cultures of normal rat adrenocortical cells were treated with agents which stimulate steroidogenesis by Y-1 adrenal tumour cells. Choleragen was active, whereas cyclic nucleotides other than cyclic AMP, bacterial endotoxins and antimicrotubular agents were inactive.", "contents": "Monolayer cultures of normal adult rat adrenocortical cells: steroidogenic responses to nucleotides, bacterial toxins and antimicrotubular agents. Monolayer cultures of normal rat adrenocortical cells were treated with agents which stimulate steroidogenesis by Y-1 adrenal tumour cells. Choleragen was active, whereas cyclic nucleotides other than cyclic AMP, bacterial endotoxins and antimicrotubular agents were inactive."} {"id": "PMID:178526", "title": "Regulatory properties of the citrate synthase from Rhodospirillum rubrum.", "content": "Citrate synthase, purified 600-fold from Rhodospirillum rubrum, is activated by KCl and inhibited by ATP and NADH; the effect of the latter inhibitor is completely counteracted by AMP and partially counteracted by KCl.", "contents": "Regulatory properties of the citrate synthase from Rhodospirillum rubrum. Citrate synthase, purified 600-fold from Rhodospirillum rubrum, is activated by KCl and inhibited by ATP and NADH; the effect of the latter inhibitor is completely counteracted by AMP and partially counteracted by KCl."} {"id": "PMID:178527", "title": "Increase in membrane conductance by adrenaline in parotid acinar cells.", "content": "It is shown that excitation of the alpha- or beta-adrenoceptors in mouse parotid acinar cells causes a marked reduction of surface cell membrane resistance. The alpha-adrenoceptor induced membrane effect is an increase in K conductance. The beta-adrenoceptor induced membrane effect does not seem to be mediated by cyclic AMP.", "contents": "Increase in membrane conductance by adrenaline in parotid acinar cells. It is shown that excitation of the alpha- or beta-adrenoceptors in mouse parotid acinar cells causes a marked reduction of surface cell membrane resistance. The alpha-adrenoceptor induced membrane effect is an increase in K conductance. The beta-adrenoceptor induced membrane effect does not seem to be mediated by cyclic AMP."} {"id": "PMID:178528", "title": "Tumor incidence in Visna virus inoculated mice.", "content": "Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8-12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in non-infected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma.", "contents": "Tumor incidence in Visna virus inoculated mice. Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8-12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in non-infected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma."} {"id": "PMID:178529", "title": "Chromatographic conditions in the expression of corticosteroid receptor specificity.", "content": "It is shown that cytosol preparations bound with various concentrations of a steroid are necessary to reveal physicochemically distinct, heterogeneous and polymorphic receptors present in the hormone specific target organ, that these cannot be fully appreciated in one-shot experiments at suboptimal steroids levels, and that they escape detection by equilibrium binding and Scatchard analysis alone.", "contents": "Chromatographic conditions in the expression of corticosteroid receptor specificity. It is shown that cytosol preparations bound with various concentrations of a steroid are necessary to reveal physicochemically distinct, heterogeneous and polymorphic receptors present in the hormone specific target organ, that these cannot be fully appreciated in one-shot experiments at suboptimal steroids levels, and that they escape detection by equilibrium binding and Scatchard analysis alone."} {"id": "PMID:178548", "title": "Changes in the protein conformation of human spermatozoal membranes after treatment with cyclic adenosine 3':5'-monophosphate and human follicular fluid.", "content": "Infrared spectra in the amide I and amide II regions of acrosomal membranes isolated from ejaculated human spermatozoa indicate the presence of a high proportion of the constitutive proteins in the most stable protein configuration, the antiparallel beta-conformation. Since the infrared spectra obtained with the membranes suspended in D2O or after extraction of the lipid components do not show any significant change, it can be postulated that the antiparallel pleated sheet conformation of human spermatozoal membrane proteins is independent of the hydrated state and of the lipid constitution of the membrane.", "contents": "Changes in the protein conformation of human spermatozoal membranes after treatment with cyclic adenosine 3':5'-monophosphate and human follicular fluid. Infrared spectra in the amide I and amide II regions of acrosomal membranes isolated from ejaculated human spermatozoa indicate the presence of a high proportion of the constitutive proteins in the most stable protein configuration, the antiparallel beta-conformation. Since the infrared spectra obtained with the membranes suspended in D2O or after extraction of the lipid components do not show any significant change, it can be postulated that the antiparallel pleated sheet conformation of human spermatozoal membrane proteins is independent of the hydrated state and of the lipid constitution of the membrane."} {"id": "PMID:178549", "title": "[Membrane defect as a basic disorder of the growth control mechanism in psoriasis pathogenetic concept and therapeutic consequences (author's transl)].", "content": "The system glycocalyz - membrane bound enzymes - cAMP may be regarded as a regulatory mechanism for the control of epidermal growth. The glycocalyz of the epithelial cell membrane is obviously a receptor and accumulator for agents stimulating adenyl cyclase and other membrane-bound enzymes of energy utilisation; cAMP, on the other hand, serves as an intracellular 'mediator' between proliferative stimuli and the DNA of the keratinocytes. Numerous cytological, cytochemical, and enzymatic biochemical studies indicate that this mechanism is profoundly disturbed in psoriasis, particularly at the membrane-bound stage.", "contents": "[Membrane defect as a basic disorder of the growth control mechanism in psoriasis pathogenetic concept and therapeutic consequences (author's transl)]. The system glycocalyz - membrane bound enzymes - cAMP may be regarded as a regulatory mechanism for the control of epidermal growth. The glycocalyz of the epithelial cell membrane is obviously a receptor and accumulator for agents stimulating adenyl cyclase and other membrane-bound enzymes of energy utilisation; cAMP, on the other hand, serves as an intracellular 'mediator' between proliferative stimuli and the DNA of the keratinocytes. Numerous cytological, cytochemical, and enzymatic biochemical studies indicate that this mechanism is profoundly disturbed in psoriasis, particularly at the membrane-bound stage."} {"id": "PMID:178553", "title": "Enzymatic activities in mitochondria isolated from the rat brain during development.", "content": "In an attempt to discern whether mitochondrial changes during ontogeny are due to increases in number of mitochondria or to increases in number plus changes in their organization, we investigated the enzymatic markers of the inner and outer membranes of mitochondria from cerebral cortex and subcortical material in young and adult rats. We conclude from the data gathered that significant changes do occur in mitochondrial organization, that gradual maturation occurs in the inner membrane during development, especially in the cerebral cortex and considerably less so in the subcortical structures. We found no such changes in the sturucture of the outer membrane during the periods of development examined.", "contents": "Enzymatic activities in mitochondria isolated from the rat brain during development. In an attempt to discern whether mitochondrial changes during ontogeny are due to increases in number of mitochondria or to increases in number plus changes in their organization, we investigated the enzymatic markers of the inner and outer membranes of mitochondria from cerebral cortex and subcortical material in young and adult rats. We conclude from the data gathered that significant changes do occur in mitochondrial organization, that gradual maturation occurs in the inner membrane during development, especially in the cerebral cortex and considerably less so in the subcortical structures. We found no such changes in the sturucture of the outer membrane during the periods of development examined."} {"id": "PMID:178554", "title": "Insulin receptors in cultured human fibroblasts.", "content": "In order to study human insulin resistance, we have first characterized the interaction of insulin with specific insulin receptors in cultures of normal human fibroblasts. 125 I-insulin bound rapidly to human fibroblasts in suspension at 15 degrees, achieving steady state between one and three hours. Insulin was not degraded during the binding assays. In competitive binding experiments, 2 ng/ml. (3.3 X 10(-10) M) of unlabeled insulin reduced 125 I-insulin binding by 50 per cent. Insulin analogues competed for binding in proportion to their biologic potencies. A curvilinear Scatchard plot was obtained, suggesting the existence of negatively cooperative site-site interactions among the insulin receptors. This was confirmed directly by studies of the dissociation kinetics. The high affinity, specificity, and negative cooperativity of the fibroblast insulin receptor closely resembles the properties of other human insulin receptors. The cultuted human fibroblast should prove a useful tissue for the study of insulin-resistant states in man.", "contents": "Insulin receptors in cultured human fibroblasts. In order to study human insulin resistance, we have first characterized the interaction of insulin with specific insulin receptors in cultures of normal human fibroblasts. 125 I-insulin bound rapidly to human fibroblasts in suspension at 15 degrees, achieving steady state between one and three hours. Insulin was not degraded during the binding assays. In competitive binding experiments, 2 ng/ml. (3.3 X 10(-10) M) of unlabeled insulin reduced 125 I-insulin binding by 50 per cent. Insulin analogues competed for binding in proportion to their biologic potencies. A curvilinear Scatchard plot was obtained, suggesting the existence of negatively cooperative site-site interactions among the insulin receptors. This was confirmed directly by studies of the dissociation kinetics. The high affinity, specificity, and negative cooperativity of the fibroblast insulin receptor closely resembles the properties of other human insulin receptors. The cultuted human fibroblast should prove a useful tissue for the study of insulin-resistant states in man."} {"id": "PMID:178555", "title": "Cyclic nucleotides in pancreatic islets. Tolbutamide- and arginine-induced insulin release.", "content": "With the use of isolated rat islet perfusion, levels of the islet cyclic adenosine 3' ,5' -monophosphate (cAMP) were compared with dynamic insulin secretion induced by tolbutamide and arginine. Tolbutamide elevated islet cAMP rapidly and augmented both glucose-induced islet cAMP levels and insulin secretion; arginine, however, did not elevate islet cAMP but did enhance glucose-induced insulin secretion. Since the latter result could have been modulated by cyclic guanosine 3' ,5' -monophosphate, this cyclic nucleotide was also measured and found to remain unchanged during stimulation of insulin secretion by arginine and a combination or arginine and glucose. Thus, the action of tolbutamide appears to be modulated in part by cAMP, whereas arginine appears to augment insulin secretion independently of cyclic nucleotides.", "contents": "Cyclic nucleotides in pancreatic islets. Tolbutamide- and arginine-induced insulin release. With the use of isolated rat islet perfusion, levels of the islet cyclic adenosine 3' ,5' -monophosphate (cAMP) were compared with dynamic insulin secretion induced by tolbutamide and arginine. Tolbutamide elevated islet cAMP rapidly and augmented both glucose-induced islet cAMP levels and insulin secretion; arginine, however, did not elevate islet cAMP but did enhance glucose-induced insulin secretion. Since the latter result could have been modulated by cyclic guanosine 3' ,5' -monophosphate, this cyclic nucleotide was also measured and found to remain unchanged during stimulation of insulin secretion by arginine and a combination or arginine and glucose. Thus, the action of tolbutamide appears to be modulated in part by cAMP, whereas arginine appears to augment insulin secretion independently of cyclic nucleotides."} {"id": "PMID:178556", "title": "Some considerations in the preparation of raioiodoinsulin for radioimmunoassay and receptor assay.", "content": "125I-insulins, prepared by iodination with chloramine T in marked excess or by stepwise, stoichiometric addition of the oxidizing agent, were compared with respect both to their molecular distribution of iodine and to their suitability for use in a cultured lymphocyte receptor assay. Iodination of insulin in aqueous solution results in the same distribution of iodine atoms, independent of experimental method and dependent only on the average iodine number. This distribution can be calculated on the basis of a Monte Carlo simulation, For insulin iodinated at an average of 0.8 I atoms per molecule, approximately 50 per cent of the radioactivity is in other than monoiodoninsulin. Purification methods that separate on the basis of charge, such as starch-gel electrophoresis, are then required, to obtain monoiodoinsulin. More highly iodinated insulin do bind to the lymphocyte receptor, although, as in radioimmunoassay, the overiodinated species are less satisfactory for use as tracers. The shelf life of iodinated insulin appears to be related better to the average iodine content than to any other factor, presumably because of decay catastrophe. There is no evidence to suggest that exposure to chloramine T in marked excess for a few seconds is deleterious to insulin.", "contents": "Some considerations in the preparation of raioiodoinsulin for radioimmunoassay and receptor assay. 125I-insulins, prepared by iodination with chloramine T in marked excess or by stepwise, stoichiometric addition of the oxidizing agent, were compared with respect both to their molecular distribution of iodine and to their suitability for use in a cultured lymphocyte receptor assay. Iodination of insulin in aqueous solution results in the same distribution of iodine atoms, independent of experimental method and dependent only on the average iodine number. This distribution can be calculated on the basis of a Monte Carlo simulation, For insulin iodinated at an average of 0.8 I atoms per molecule, approximately 50 per cent of the radioactivity is in other than monoiodoninsulin. Purification methods that separate on the basis of charge, such as starch-gel electrophoresis, are then required, to obtain monoiodoinsulin. More highly iodinated insulin do bind to the lymphocyte receptor, although, as in radioimmunoassay, the overiodinated species are less satisfactory for use as tracers. The shelf life of iodinated insulin appears to be related better to the average iodine content than to any other factor, presumably because of decay catastrophe. There is no evidence to suggest that exposure to chloramine T in marked excess for a few seconds is deleterious to insulin."} {"id": "PMID:178557", "title": "Diabetes mellitus in the guinea pig.", "content": "Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus.", "contents": "Diabetes mellitus in the guinea pig. Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus."} {"id": "PMID:178559", "title": "Preparative action of carbon tetrachloride in liver tumorigenesis by a single application of N-butylnitrosourea in male ICR/JCL strain mice.", "content": "A dose of 10 or 20 mg of N-butylnitrosourea (BNU) dissolved in 50% ethanol was administered by a gastric tube to 6-week-old male ICR/JCL strain mice and they were sacrificed 15 months later. One of 18 animals developed a hepatoma, but none of the mice given CCl4 in 0.1 ml of 50% oliver oil subcutaneously at the right thigh developed hepatoma. However, a marked enhancement of hepatoma induction was observed in mice injected with CCl4 one day before the single intragastric administration of BNU, with 12 out of 28 mice developing one or more hepatomas (average 3.2/mouse) ranging in diameter from 0.5 to 1.5 cm. By extending the administration interval between CCl4 and BNU to 1 week or 1 month, or by reversing the order of administration, the hepatotumorigenic action was virtually lost. There was no occurrence of hepatoma but a predominant development of leukemia, of either thymic or nonthymic origin, was observed in mice of younger age treated with CCl4 one day before continuous oral administration of BNU (1 mg/day/mouse). It is thus concluded that the preparative (cocarcinogenic) action of CCl4 is indispensable for hepatotumorigenesis with a single large dose of BNU.", "contents": "Preparative action of carbon tetrachloride in liver tumorigenesis by a single application of N-butylnitrosourea in male ICR/JCL strain mice. A dose of 10 or 20 mg of N-butylnitrosourea (BNU) dissolved in 50% ethanol was administered by a gastric tube to 6-week-old male ICR/JCL strain mice and they were sacrificed 15 months later. One of 18 animals developed a hepatoma, but none of the mice given CCl4 in 0.1 ml of 50% oliver oil subcutaneously at the right thigh developed hepatoma. However, a marked enhancement of hepatoma induction was observed in mice injected with CCl4 one day before the single intragastric administration of BNU, with 12 out of 28 mice developing one or more hepatomas (average 3.2/mouse) ranging in diameter from 0.5 to 1.5 cm. By extending the administration interval between CCl4 and BNU to 1 week or 1 month, or by reversing the order of administration, the hepatotumorigenic action was virtually lost. There was no occurrence of hepatoma but a predominant development of leukemia, of either thymic or nonthymic origin, was observed in mice of younger age treated with CCl4 one day before continuous oral administration of BNU (1 mg/day/mouse). It is thus concluded that the preparative (cocarcinogenic) action of CCl4 is indispensable for hepatotumorigenesis with a single large dose of BNU."} {"id": "PMID:178560", "title": "Lack of correlation between the presence of estrogen receptor and histological type of mammary cancer induced by 7,12-dimethylbenz[alpha]anthracene.", "content": "The relation between the histological type and the presence of estrogen receptor or response to oophorectomy was investigated in the mammary cancer induced by 7,12-dimethylbenz[alpha]anthracene in Spargue-Dawley rats. The estrogen receptor was present in 75.0% (3/4) of poorly differentiated cancer and in 62.5% (10/16) of well-differentiated cancer. The histological degree of differentiation or grading of the rat mammary cancer did not affect the presence of the estrogen receptor or response to oophorectomy. In contrast, there was clearly a good correlation between the presence of the receptor and response to oophorectomy.", "contents": "Lack of correlation between the presence of estrogen receptor and histological type of mammary cancer induced by 7,12-dimethylbenz[alpha]anthracene. The relation between the histological type and the presence of estrogen receptor or response to oophorectomy was investigated in the mammary cancer induced by 7,12-dimethylbenz[alpha]anthracene in Spargue-Dawley rats. The estrogen receptor was present in 75.0% (3/4) of poorly differentiated cancer and in 62.5% (10/16) of well-differentiated cancer. The histological degree of differentiation or grading of the rat mammary cancer did not affect the presence of the estrogen receptor or response to oophorectomy. In contrast, there was clearly a good correlation between the presence of the receptor and response to oophorectomy."} {"id": "PMID:178561", "title": "Intracisternal A particles in transplantable reticulum cell sarcoma of rats.", "content": "Electron microscopic examination on three lines of transplantable reticulum cell sarcomas, induced spontaneously in the mesenteric lymph nodes of inbred strain ACI rats, proved the presence of intracisternal A particles in all the three tumor lines. The doughnut-shaped particles measured 50 to 70 nm and were seen to bud from the membranes of rough-surfaced endoplasmic reticulum. Frequency of appearance of these particles varied with the tumor line.", "contents": "Intracisternal A particles in transplantable reticulum cell sarcoma of rats. Electron microscopic examination on three lines of transplantable reticulum cell sarcomas, induced spontaneously in the mesenteric lymph nodes of inbred strain ACI rats, proved the presence of intracisternal A particles in all the three tumor lines. The doughnut-shaped particles measured 50 to 70 nm and were seen to bud from the membranes of rough-surfaced endoplasmic reticulum. Frequency of appearance of these particles varied with the tumor line."} {"id": "PMID:178562", "title": "Possible retention of the estrogen-binding capacity after endocrine ablation therapy in the rat and human breast cancer.", "content": "The estrogen-binding capacity of the regrowing tumors after endocrine ablation surgery was estimated in the rat and human breast cancer. All of 4 tumors that had not had the estrogen receptor before oophorectomy did not show the estrogen-binding capacity after the procedure, in the mammary cancer in the Sprague-Dawley rat induced by 7,12-dimethylbenz[a]anthracene, whereas all the 4 tumors that had the receptor before the procedure showed the binding capacity after oophorectomy. In 4 patients who had been subjected to the major endocrine ablation therapy because of metastatic breast cancer with effective response, the secondary metastatic deposits of cancer showed the estrogen-binding capacity long after the endocrine ablation. The fact that regrowing tumors after complete or partial regression of initial tumors by endocrine ablation retain the estrogen receptor seems to be contradictory to the classical concept of autonomy in recurrence of the breast cancer after hormonal manipulation.", "contents": "Possible retention of the estrogen-binding capacity after endocrine ablation therapy in the rat and human breast cancer. The estrogen-binding capacity of the regrowing tumors after endocrine ablation surgery was estimated in the rat and human breast cancer. All of 4 tumors that had not had the estrogen receptor before oophorectomy did not show the estrogen-binding capacity after the procedure, in the mammary cancer in the Sprague-Dawley rat induced by 7,12-dimethylbenz[a]anthracene, whereas all the 4 tumors that had the receptor before the procedure showed the binding capacity after oophorectomy. In 4 patients who had been subjected to the major endocrine ablation therapy because of metastatic breast cancer with effective response, the secondary metastatic deposits of cancer showed the estrogen-binding capacity long after the endocrine ablation. The fact that regrowing tumors after complete or partial regression of initial tumors by endocrine ablation retain the estrogen receptor seems to be contradictory to the classical concept of autonomy in recurrence of the breast cancer after hormonal manipulation."} {"id": "PMID:178563", "title": "Histological grading, histochemistry, and electron microscopy of scirrhous carcinoma of the breast.", "content": "Twenty-six scirrhous carcinomas of the breast were divided into three histological grades of malignancy; low (Grade I), intermediate (Grade II), and high (Grade III), and the correlation of the grades with histochemical and electron microscopic findings in both tumor cells and host tissues was examined. The tumor cells contained increased amounts of lysosomal acid phosphatase and beta-glucuronidase. This increase was most marked in Grade I and II tumors and the increase was consistent with lysosome-like fine structures. Both intracytoplasmic lumina and microvilli against stroma were characteristic findings of carcinoma cells and they were mostly found in Grade I and II tumors. Segments of intact basal laminae and myoepithelial cells were also found in Grade I and II carcinomas. The stroma contained moderately increased amounts of intracellular acid phosphatase and beta-glucuronidase, independent of tumor grade. The stroma also contained a large amount of acid mucopolysaccharide ground substance, irrespective of the three grades. There was a striking difference in the ultrastructural organization of the stroma between normal and neoplastic tissues. Although fragmented elastic fibers and increased amount of acid mucopolysaccharide granules, and macrophages rich in phagolysosomes were prominent fine structures of the stroma of carcinomas, there was no apparent difference in them among the three grades of malignancy.", "contents": "Histological grading, histochemistry, and electron microscopy of scirrhous carcinoma of the breast. Twenty-six scirrhous carcinomas of the breast were divided into three histological grades of malignancy; low (Grade I), intermediate (Grade II), and high (Grade III), and the correlation of the grades with histochemical and electron microscopic findings in both tumor cells and host tissues was examined. The tumor cells contained increased amounts of lysosomal acid phosphatase and beta-glucuronidase. This increase was most marked in Grade I and II tumors and the increase was consistent with lysosome-like fine structures. Both intracytoplasmic lumina and microvilli against stroma were characteristic findings of carcinoma cells and they were mostly found in Grade I and II tumors. Segments of intact basal laminae and myoepithelial cells were also found in Grade I and II carcinomas. The stroma contained moderately increased amounts of intracellular acid phosphatase and beta-glucuronidase, independent of tumor grade. The stroma also contained a large amount of acid mucopolysaccharide ground substance, irrespective of the three grades. There was a striking difference in the ultrastructural organization of the stroma between normal and neoplastic tissues. Although fragmented elastic fibers and increased amount of acid mucopolysaccharide granules, and macrophages rich in phagolysosomes were prominent fine structures of the stroma of carcinomas, there was no apparent difference in them among the three grades of malignancy."} {"id": "PMID:178564", "title": "Electron microscopy of C-particles and small vesicles in a transplantable rat ascites hepatoma-66F.", "content": "Transplantable rat ascites hepatoma AH-66F was examined by an electron microscope. C-particles were numerously observed in the intercellular spaces and on the cell surface. The size of these particles varied from 90 to 200 nm in diameter. Small vesicles were also observed. These vesicles ranged from 40 to 50 nm in diameter. Most of them were located near the group of C-particles. Occasionally, small vesicles were observed in the form of a rosette around the C-particles.", "contents": "Electron microscopy of C-particles and small vesicles in a transplantable rat ascites hepatoma-66F. Transplantable rat ascites hepatoma AH-66F was examined by an electron microscope. C-particles were numerously observed in the intercellular spaces and on the cell surface. The size of these particles varied from 90 to 200 nm in diameter. Small vesicles were also observed. These vesicles ranged from 40 to 50 nm in diameter. Most of them were located near the group of C-particles. Occasionally, small vesicles were observed in the form of a rosette around the C-particles."} {"id": "PMID:178565", "title": "Influence of sex hormones on kidney tumors induced in rats with N-butylnitrosourea.", "content": "A total 39 kidney tumors were induced by a continuous oral administration of N-butylnitrosourea (BNU) in 33 out of 204 rats of W/Fu strain and of 41 (W/Fu X ACI/N)F1 rats. No spontaneous renal tumors were observed among 66 males and 109 females of W/Fu rats which survived beyond the age of 19 months. Histologically, renal cell and mesenchymal types were commonly observed; 24 cases belonging to the former and 11 cases to the latter. Two cases of nephroblastoma were also encountered. There was no sex difference in renal tumorigenesis with BNU as a whole. Castration in both sexes was apparently inhibitory for kidney tumor development. Estrogenization of castrated rats either by syngeneic ovary graft or by repeated injections of estradiol benzoate enhanced tumor induction with BNU. Progesterone was not effective in restoring the tumor incidence in castrated rats. Distribution of histological types of tumors thus induced differed among the hosts with different hormonal conditions; in males the majority was renal cell type, whereas almost all mesenchymal tumor and nephroblastoma cases were found in intact females or estrogenized rats. BNU induced a variety of tumors in several organs including cerebral hemisphere, peripheral nerves, mammary glands, hematopoietic system, digestive tracts, and so on. However, such concurrence did not affect the development of renal tumors in the present study.", "contents": "Influence of sex hormones on kidney tumors induced in rats with N-butylnitrosourea. A total 39 kidney tumors were induced by a continuous oral administration of N-butylnitrosourea (BNU) in 33 out of 204 rats of W/Fu strain and of 41 (W/Fu X ACI/N)F1 rats. No spontaneous renal tumors were observed among 66 males and 109 females of W/Fu rats which survived beyond the age of 19 months. Histologically, renal cell and mesenchymal types were commonly observed; 24 cases belonging to the former and 11 cases to the latter. Two cases of nephroblastoma were also encountered. There was no sex difference in renal tumorigenesis with BNU as a whole. Castration in both sexes was apparently inhibitory for kidney tumor development. Estrogenization of castrated rats either by syngeneic ovary graft or by repeated injections of estradiol benzoate enhanced tumor induction with BNU. Progesterone was not effective in restoring the tumor incidence in castrated rats. Distribution of histological types of tumors thus induced differed among the hosts with different hormonal conditions; in males the majority was renal cell type, whereas almost all mesenchymal tumor and nephroblastoma cases were found in intact females or estrogenized rats. BNU induced a variety of tumors in several organs including cerebral hemisphere, peripheral nerves, mammary glands, hematopoietic system, digestive tracts, and so on. However, such concurrence did not affect the development of renal tumors in the present study."} {"id": "PMID:178566", "title": "Collagenolytic enzyme in solid Tawa sarcoma.", "content": "In order to demonstrate a collagenolytic enzyme in a tumor, solid Tawa sarcoma was subjected to a tissue culture technique. Salt- and acid-soluble collagen used as substrate was extracted from the rat skin and tail tendon. The tumor mass used was obtained on the 5th, 8th, and 11th days after subcutaneous transplantation of ascites Tawa sarcoma cells. Each tissue fragment in the inner and outer layers of the tumor mass was incubated on collagen gel at 37 degrees for 4 days, and collagenolytic activity was determined by comparing the relative content of hydroxyproline in the attacked collagen which was separated by means of centrifugation. All fragments were found to possess collagenolytic activity with some variation. Higher activity was observed in the outer layer than in the inner layer. Tumor fragments were cultured, and the collagenolytic enzyme was isolated from the culture medium and concentrated by ammonium sulfate precipitation and acrylamide disc electrophoresis. Collagenolytic enzyme activity was examined for its mode of attack on native collagen.", "contents": "Collagenolytic enzyme in solid Tawa sarcoma. In order to demonstrate a collagenolytic enzyme in a tumor, solid Tawa sarcoma was subjected to a tissue culture technique. Salt- and acid-soluble collagen used as substrate was extracted from the rat skin and tail tendon. The tumor mass used was obtained on the 5th, 8th, and 11th days after subcutaneous transplantation of ascites Tawa sarcoma cells. Each tissue fragment in the inner and outer layers of the tumor mass was incubated on collagen gel at 37 degrees for 4 days, and collagenolytic activity was determined by comparing the relative content of hydroxyproline in the attacked collagen which was separated by means of centrifugation. All fragments were found to possess collagenolytic activity with some variation. Higher activity was observed in the outer layer than in the inner layer. Tumor fragments were cultured, and the collagenolytic enzyme was isolated from the culture medium and concentrated by ammonium sulfate precipitation and acrylamide disc electrophoresis. Collagenolytic enzyme activity was examined for its mode of attack on native collagen."} {"id": "PMID:178568", "title": "Cimetidine inhibits caffeine-stimulated gastric acid secretion in man.", "content": "In animals, gastric acid secretion stimulated by the methyl xanthine, theophylline, was not inhibited by histamine H2-receptor antagonists. In this study the effect in man of the H2-receptor antagonist, cimetidine, on gastric acid secretion stimulated by the methyl xanthine, caffeine, was examined. Caffeine was given intravenously for 2 hr in a dose of 9 mg per kg-hr to 5 patients with duodenal ulcer and 5 normal subjects. Three hundred milligrams of cimetidine administered orally 30 min before the start of the caffeine infusion completely abolished the acid secretory response in all subjects, decreasing acid secretion to less than basal rates. It is concluded that in man the H2-receptor antagonist, cimetidine, abolished the acid secretory response to the methyl xanthine, caffeine.", "contents": "Cimetidine inhibits caffeine-stimulated gastric acid secretion in man. In animals, gastric acid secretion stimulated by the methyl xanthine, theophylline, was not inhibited by histamine H2-receptor antagonists. In this study the effect in man of the H2-receptor antagonist, cimetidine, on gastric acid secretion stimulated by the methyl xanthine, caffeine, was examined. Caffeine was given intravenously for 2 hr in a dose of 9 mg per kg-hr to 5 patients with duodenal ulcer and 5 normal subjects. Three hundred milligrams of cimetidine administered orally 30 min before the start of the caffeine infusion completely abolished the acid secretory response in all subjects, decreasing acid secretion to less than basal rates. It is concluded that in man the H2-receptor antagonist, cimetidine, abolished the acid secretory response to the methyl xanthine, caffeine."} {"id": "PMID:178569", "title": "Activation of intestinal mucosal adenylate cyclase by Shigella dysenteriae I enterotoxin.", "content": "Because the mechanism whereby Shigella dysenteriae I enterotoxin induces intestinal secretion is unclear, the effect of this toxin on adenylate cyclase activity in rabbit ileal mucosa was studied under various in vitro and in vivo conditions. Activation of adenylate cyclase by Shigella enterotoxin was observed only when substrate (ATP) concentrations above the Km of adenylate cyclase were employed. These concentrations of ATP are greater than those required to demonstrate activation of adenylate cyclase by cholera toxin. Under optimal assay conditions, doses of Shigella toxin between 5.4 and 900 mug of toxin protein and in vivo incubation times between 6 and 18 hr all increased adenylate cyclase activity by about 100%. Shigella toxin produced significant but highly variable increases in mucosal cyclic AMP concentrations, which were less that the rises seen with a comparable dose of cholera toxin. This variability in cyclic AMP response to Shigella toxin and the disparity between Shigella and cholera toxins' effects on mucosal cyclic AMP are probably the result of the different kinetics of adenylate cyclase activated by these enterotoxins. Mucosal Na-K-ATPase activity was unaffected by Shigella toxin. These observations suggest that alterations in fluid and electrolyte transport induced by Shigella enterotoxin may, in part, be mediated by the adenylate cyclase-cyclic AMP system.", "contents": "Activation of intestinal mucosal adenylate cyclase by Shigella dysenteriae I enterotoxin. Because the mechanism whereby Shigella dysenteriae I enterotoxin induces intestinal secretion is unclear, the effect of this toxin on adenylate cyclase activity in rabbit ileal mucosa was studied under various in vitro and in vivo conditions. Activation of adenylate cyclase by Shigella enterotoxin was observed only when substrate (ATP) concentrations above the Km of adenylate cyclase were employed. These concentrations of ATP are greater than those required to demonstrate activation of adenylate cyclase by cholera toxin. Under optimal assay conditions, doses of Shigella toxin between 5.4 and 900 mug of toxin protein and in vivo incubation times between 6 and 18 hr all increased adenylate cyclase activity by about 100%. Shigella toxin produced significant but highly variable increases in mucosal cyclic AMP concentrations, which were less that the rises seen with a comparable dose of cholera toxin. This variability in cyclic AMP response to Shigella toxin and the disparity between Shigella and cholera toxins' effects on mucosal cyclic AMP are probably the result of the different kinetics of adenylate cyclase activated by these enterotoxins. Mucosal Na-K-ATPase activity was unaffected by Shigella toxin. These observations suggest that alterations in fluid and electrolyte transport induced by Shigella enterotoxin may, in part, be mediated by the adenylate cyclase-cyclic AMP system."} {"id": "PMID:178570", "title": "[Reasons for development of chromosome aberrations in cells of a culture of human embryonal fibroblasts infected with herpes simplex virus].", "content": "The object of this investigation was the role of lysosomic and virus-induced aberrations in cells of the culture of embryonic human fibroblasts infected with herpes simplex virus. It was established that the frequency of cells with chromosomal abnormalities in infected cultures in 4 and 9 hours after infection was 15,2% and 23,7% respectively, being 2% in the control culture. Stablization of lysosomal membranes with hydrocortisone or the inhibition of lysosome enzymes by trypan blue resulted in the decrease of the proportion of aberrant cells down to the control level in 4 hours after the infection, while in 9 hours after the infection it was higher, than in the control, although significantly lower, than in the cultures infected with the virus, but not subjected to any treatment suppressing the mutagenic effect of the virus. The suppression of the transcription of the viral genome by actinomycin D did not decrease the proportion of aberrant cells in 4 hours after the infection, while in 9 hours after the infection it was significantly lower, than in the infected cultures not treated with actinomycin D, but higher, than in the control. Simultaneous suppression of the effect of virus-induced enzymes by actinomycin D and lysosome enzymes by hydrocortisone or trypan blue decreased efficiently the proportion of aberrant cells down to the control level both after 4 and after 9 hours following the infection. Apparently chromosome aberrations in embryonic human fibroblasts infected with herpes simplex virus are caused both by lysosomal and by virus-induced enzymes. Possibly in different virus-cell systems the relative role of these two factors can be considerably different from one another.", "contents": "[Reasons for development of chromosome aberrations in cells of a culture of human embryonal fibroblasts infected with herpes simplex virus]. The object of this investigation was the role of lysosomic and virus-induced aberrations in cells of the culture of embryonic human fibroblasts infected with herpes simplex virus. It was established that the frequency of cells with chromosomal abnormalities in infected cultures in 4 and 9 hours after infection was 15,2% and 23,7% respectively, being 2% in the control culture. Stablization of lysosomal membranes with hydrocortisone or the inhibition of lysosome enzymes by trypan blue resulted in the decrease of the proportion of aberrant cells down to the control level in 4 hours after the infection, while in 9 hours after the infection it was higher, than in the control, although significantly lower, than in the cultures infected with the virus, but not subjected to any treatment suppressing the mutagenic effect of the virus. The suppression of the transcription of the viral genome by actinomycin D did not decrease the proportion of aberrant cells in 4 hours after the infection, while in 9 hours after the infection it was significantly lower, than in the infected cultures not treated with actinomycin D, but higher, than in the control. Simultaneous suppression of the effect of virus-induced enzymes by actinomycin D and lysosome enzymes by hydrocortisone or trypan blue decreased efficiently the proportion of aberrant cells down to the control level both after 4 and after 9 hours following the infection. Apparently chromosome aberrations in embryonic human fibroblasts infected with herpes simplex virus are caused both by lysosomal and by virus-induced enzymes. Possibly in different virus-cell systems the relative role of these two factors can be considerably different from one another."} {"id": "PMID:178571", "title": "[Mutagenesis under the influence of simian vacuolating virus 40 (SV40). I. Induction of chromosome aberrations in Chinese hamster cells during the first days following infection].", "content": "Chromosome aberrations were studied in cultured chinese hamster cells on the 1--4th days after infection with Simian Virus 40. In the first and second mitoses after infection a statistically significant increase of the percentage of aberrant metaphases was observed (up to 22% as compared to 8--10% in intact cells). Already after 3 days following treatment the percentage of aberrant metaphases decreased sharply, reaching the control level. The virus induced a significant increase of the frequency of chromosome and chromatid breaks, as well as the appearance of fragments of an unknown origin. Chromosome breaks were distributed randomly among 5 morphologically distinct chromosome groups, according to the comparative length of respective chromosomes. An increase of the frequency of gaps and coiling deficiencies was also observed in virus-infected cultures. An earlier appearance of the first mitosis was observed in virus-treated cultures. It is suggested that the mutagenic effect of SV40 in the cells studied may be related to mechanisms controlling the integration of viral genomes into the cell chromosomes.", "contents": "[Mutagenesis under the influence of simian vacuolating virus 40 (SV40). I. Induction of chromosome aberrations in Chinese hamster cells during the first days following infection]. Chromosome aberrations were studied in cultured chinese hamster cells on the 1--4th days after infection with Simian Virus 40. In the first and second mitoses after infection a statistically significant increase of the percentage of aberrant metaphases was observed (up to 22% as compared to 8--10% in intact cells). Already after 3 days following treatment the percentage of aberrant metaphases decreased sharply, reaching the control level. The virus induced a significant increase of the frequency of chromosome and chromatid breaks, as well as the appearance of fragments of an unknown origin. Chromosome breaks were distributed randomly among 5 morphologically distinct chromosome groups, according to the comparative length of respective chromosomes. An increase of the frequency of gaps and coiling deficiencies was also observed in virus-infected cultures. An earlier appearance of the first mitosis was observed in virus-treated cultures. It is suggested that the mutagenic effect of SV40 in the cells studied may be related to mechanisms controlling the integration of viral genomes into the cell chromosomes."} {"id": "PMID:178572", "title": "[Mutagenesis under the influence of simian virus 40 (SV40). II. Induct?ION OF MUTATIONS RESULTING IN RESISTANCE TO PURINE BASE ANALOGS IN HUMAN AND Chinese hamster cells].", "content": "Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cell lines. It is shown that SV40 penetrates into the cells studied and induces the T-antigen synthesis. The efficiency of the infection in Chinese hamster cells was tested additionally by the ability of infected cells to form colonies in the medium lacking serum growth factor. The maximal number of colony-forming cells was detected 24 hours after the infection. By culturing cells in factor-free medium a Chinese hamster cell subline was isolated, which proved to synthetize T-antigen within 60 days after the virus treatment. This is regarded as an indirect proof of the integration of viral genome into the cell genome. The increased frequency of mutants resistant to 60 mkg/ml of 8-azaguanine (human cells) and to 15 mkg/ml of 6-mercaptopurine (hamster cells) was observed on the 1--4th days following the infection. The analysis of the results of all experiments taken together revealed that the induction is highly significant according to Wilcoxon (greater than 0.99). The resistance of the isolated clones proved to be stable after the prolonged culturing under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosome aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogensis and tumour progression is discussed.", "contents": "[Mutagenesis under the influence of simian virus 40 (SV40). II. Induct?ION OF MUTATIONS RESULTING IN RESISTANCE TO PURINE BASE ANALOGS IN HUMAN AND Chinese hamster cells]. Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cell lines. It is shown that SV40 penetrates into the cells studied and induces the T-antigen synthesis. The efficiency of the infection in Chinese hamster cells was tested additionally by the ability of infected cells to form colonies in the medium lacking serum growth factor. The maximal number of colony-forming cells was detected 24 hours after the infection. By culturing cells in factor-free medium a Chinese hamster cell subline was isolated, which proved to synthetize T-antigen within 60 days after the virus treatment. This is regarded as an indirect proof of the integration of viral genome into the cell genome. The increased frequency of mutants resistant to 60 mkg/ml of 8-azaguanine (human cells) and to 15 mkg/ml of 6-mercaptopurine (hamster cells) was observed on the 1--4th days following the infection. The analysis of the results of all experiments taken together revealed that the induction is highly significant according to Wilcoxon (greater than 0.99). The resistance of the isolated clones proved to be stable after the prolonged culturing under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosome aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogensis and tumour progression is discussed."} {"id": "PMID:178573", "title": "[Predominant loss of hamster chromosomes in hybrids of somatic cells from the Dzungarian hamster and mice].", "content": "By means of the application of UV-inactivated Sendai virus interspecific hybrids of Dzungarian hamsterXmouse somatic cells were obtained in HAT selective medium. Karyotypic changes in these hybrid somatic cells were recorded during a 13 months' period. In the beginning each hybrid somatic cell contained 1 chromosome set of Dzungarian hamster and 1 mouse chromosome set. It was observed that throughout 13 months' of cultivation the elimination of Dzungarian hamster chromosomes prevailed over that of mouse chromosomes.", "contents": "[Predominant loss of hamster chromosomes in hybrids of somatic cells from the Dzungarian hamster and mice]. By means of the application of UV-inactivated Sendai virus interspecific hybrids of Dzungarian hamsterXmouse somatic cells were obtained in HAT selective medium. Karyotypic changes in these hybrid somatic cells were recorded during a 13 months' period. In the beginning each hybrid somatic cell contained 1 chromosome set of Dzungarian hamster and 1 mouse chromosome set. It was observed that throughout 13 months' of cultivation the elimination of Dzungarian hamster chromosomes prevailed over that of mouse chromosomes."} {"id": "PMID:178577", "title": "Successful treatment of a malignant gastrinoma with streptozotocin.", "content": "The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.", "contents": "Successful treatment of a malignant gastrinoma with streptozotocin. The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l."} {"id": "PMID:178579", "title": "Effect of prostaglandins on cell function and multiplication of parainfluenza 3 viruses in WISH cells.", "content": "Cytotoxic effect of prostaglandins E2 and F2alpha on cells grown in vitro and the influence of these compounds on multiplication of myxovirus parainfluenza 3 were investigated. The prostaglandins were added to culture medium (0-01-10 mug/ml) 24 hr before virus infection, or for 2 and 48 hr after inoculation with viruses. WISH cells and monkey kidney cell cultures were used. No direct cytotoxic effect of prostaglandins at concentrations 0-01-1 mug/ml was found (viability, supravital staining, phase-contrast system, Nitro-BT reduction and succinic dehydrogenase tests), whereas the concentration of 10 mug/ml within 48 hr led to reduction and succinic dehydrogenase tests), whereas the concentration of 10 mug/ml within 48 hr led to partial injury of the cell population with symptoms of damage to mitochondria. Prostaglandins E2 and F2alpha inhibited multiplication of parainfluenza 3 virus at concentrations 0-1-10 mug/ml. The inhibitory effect was most pronounced if prostaglandins were added to medium for the whole period of virus multiplication i.e. for 48 hr but little or no effect was found if they were added prior to inoculation or for 2 hr after it. Inhibitory effect of prostaglandins on replication phase of viruses is suggested.", "contents": "Effect of prostaglandins on cell function and multiplication of parainfluenza 3 viruses in WISH cells. Cytotoxic effect of prostaglandins E2 and F2alpha on cells grown in vitro and the influence of these compounds on multiplication of myxovirus parainfluenza 3 were investigated. The prostaglandins were added to culture medium (0-01-10 mug/ml) 24 hr before virus infection, or for 2 and 48 hr after inoculation with viruses. WISH cells and monkey kidney cell cultures were used. No direct cytotoxic effect of prostaglandins at concentrations 0-01-1 mug/ml was found (viability, supravital staining, phase-contrast system, Nitro-BT reduction and succinic dehydrogenase tests), whereas the concentration of 10 mug/ml within 48 hr led to reduction and succinic dehydrogenase tests), whereas the concentration of 10 mug/ml within 48 hr led to partial injury of the cell population with symptoms of damage to mitochondria. Prostaglandins E2 and F2alpha inhibited multiplication of parainfluenza 3 virus at concentrations 0-1-10 mug/ml. The inhibitory effect was most pronounced if prostaglandins were added to medium for the whole period of virus multiplication i.e. for 48 hr but little or no effect was found if they were added prior to inoculation or for 2 hr after it. Inhibitory effect of prostaglandins on replication phase of viruses is suggested."} {"id": "PMID:178580", "title": "Histochemical localization of glucose-6-phosphatase and 5-nucleotidase in the digestive system of Ophiocephalus Channa punctatus.", "content": "The histochemical localization of G6Pase and 5-Nase in the digestive system of Ophiocephalus (Channa) punctatus was studied. The highest activities of these enzymes were found in the liver. Appreciable activity was also found in the anterior intestine (duodenum) and pyloric caeca. The activity faded toward the middle and posterior intestine and rectum. In the stomach the activity was moderate. The activity of 5-Nase was weaker than that of G6Pase. In the stomach the enzymes were localized in the mucosa and gastric glands. The absorptive columnar epithelial cells were the major sites of localization in the intestine. The goblet cells were negative. The G6Pase activity was associated with the cytoplasm, while the 5-Nase activity was found in the cell membranes and the nuclei.", "contents": "Histochemical localization of glucose-6-phosphatase and 5-nucleotidase in the digestive system of Ophiocephalus Channa punctatus. The histochemical localization of G6Pase and 5-Nase in the digestive system of Ophiocephalus (Channa) punctatus was studied. The highest activities of these enzymes were found in the liver. Appreciable activity was also found in the anterior intestine (duodenum) and pyloric caeca. The activity faded toward the middle and posterior intestine and rectum. In the stomach the activity was moderate. The activity of 5-Nase was weaker than that of G6Pase. In the stomach the enzymes were localized in the mucosa and gastric glands. The absorptive columnar epithelial cells were the major sites of localization in the intestine. The goblet cells were negative. The G6Pase activity was associated with the cytoplasm, while the 5-Nase activity was found in the cell membranes and the nuclei."} {"id": "PMID:178584", "title": "Pancreatic inclusions and its relation to boric acid poisoning: review of the literature and report of a case.", "content": "It is known among forensic and pediatric pathologists that the demonstration of pancreatic inclusions is considered to have diagnostic significance in cases of boric acid poisoning. Fisher was the first to suggest a causal relationship between the inclusions and boric acid toxicity. Valdes-Dapena and Arey paid particular attention to the pancreatic inclusions in reviewing the literature of cases of boric acid poisoning. They found the inclusions in 6 of the 55 autopsies. This paper describes the finding of pancreatic inclusions in a fatal case of gastro-enteritis not associated with boric acid intoxication. The nature of the inclusion bodies was studied by light and electron microscopy. Ultrastructurally, the cytoplasmic inclusions represent a non-specific autophagic cell degenerative process. Toxicological examination of postmortem blood and viscera showed no evidence of boric acid toxicity. The desirability of toxicological analysis in cases of boric acid poisoning and the restricted value of pancreatic inclusions as a diagnostic tool are emphasised.", "contents": "Pancreatic inclusions and its relation to boric acid poisoning: review of the literature and report of a case. It is known among forensic and pediatric pathologists that the demonstration of pancreatic inclusions is considered to have diagnostic significance in cases of boric acid poisoning. Fisher was the first to suggest a causal relationship between the inclusions and boric acid toxicity. Valdes-Dapena and Arey paid particular attention to the pancreatic inclusions in reviewing the literature of cases of boric acid poisoning. They found the inclusions in 6 of the 55 autopsies. This paper describes the finding of pancreatic inclusions in a fatal case of gastro-enteritis not associated with boric acid intoxication. The nature of the inclusion bodies was studied by light and electron microscopy. Ultrastructurally, the cytoplasmic inclusions represent a non-specific autophagic cell degenerative process. Toxicological examination of postmortem blood and viscera showed no evidence of boric acid toxicity. The desirability of toxicological analysis in cases of boric acid poisoning and the restricted value of pancreatic inclusions as a diagnostic tool are emphasised."} {"id": "PMID:178585", "title": "Interactions of 17beta-estradiol and L-norepinephrine on the rat uterus.", "content": "Norepinephrine increased the in vitro uptake of 3H-estradiol by the uterus of spayed rats. This effect was observed at 15 and 30 min but not at 90 min. Norepinephrine also increased the binding of 3H-estradiol by the nuclear (p less than 0.02) and the cytosol fractions (p less than 0.01) when incubated with uterine homogenates, suggesting that norepinephrine does not require the presence of the intact tissue to exert its effects. The in vivo uptake of 3H-estradiol and the determination of the number of binding sites were performed in the uterus of rats treated with estradiol and estradiol plus norepinephrine. Norepinephrine alone increased the uptake of 3H-estradiol and the number of binding sites. The highest increment in both parameters was observed in the uterus of rats treated with estradiol plus norepinephrine. The estradiol Ka of the rat uterus cytosol treated with estradiol alone or plus norepinephrine was higher than that observed in the group without estradiol, suggesting the presence of different proteins that bind estradiol. These results indicate that norepinephrine increases the entrance of estradiol into the rat uterus both in vitro and in vivo.", "contents": "Interactions of 17beta-estradiol and L-norepinephrine on the rat uterus. Norepinephrine increased the in vitro uptake of 3H-estradiol by the uterus of spayed rats. This effect was observed at 15 and 30 min but not at 90 min. Norepinephrine also increased the binding of 3H-estradiol by the nuclear (p less than 0.02) and the cytosol fractions (p less than 0.01) when incubated with uterine homogenates, suggesting that norepinephrine does not require the presence of the intact tissue to exert its effects. The in vivo uptake of 3H-estradiol and the determination of the number of binding sites were performed in the uterus of rats treated with estradiol and estradiol plus norepinephrine. Norepinephrine alone increased the uptake of 3H-estradiol and the number of binding sites. The highest increment in both parameters was observed in the uterus of rats treated with estradiol plus norepinephrine. The estradiol Ka of the rat uterus cytosol treated with estradiol alone or plus norepinephrine was higher than that observed in the group without estradiol, suggesting the presence of different proteins that bind estradiol. These results indicate that norepinephrine increases the entrance of estradiol into the rat uterus both in vitro and in vivo."} {"id": "PMID:178586", "title": "Interactions between the pituitary, thyroid and adrenal cortex during acute exposure to cold or to electric shocks in the rat.", "content": "In intact rats acclimated to 25 +/- 1 degrees C, acute exposure to cold resulted in simultaneous stimulation of TSH and ACTH secretion. The plasma TSH response to cold was identical at temperatures varying from +14 to -10 degrees C, whereas the adrenocortical response increased proportionally to the severity of cold. Acute stimulation of ACTH secretion by exposure to a stressful situation (electrical shocks) did not alter the TSH response to cold. Conversely, acute blockade of the pituitary-adrenocortical response by dexamethasone treatment did not enhance the TSH response to cold. Chronic stimulation of ACTH secretion resulting from adrenalectomy did not interfere with the TSH response during subsequent exposure to cold. However, a reduced adrenocortical response to cold was observed during chronic hypersecretion of TSH resulting from previous thyroidectomy. These findings do not support the hypothesis of an inverse relationship between TSH and ACTH secretions during acute cold exposure, but rather suggest that these secretions are independent.", "contents": "Interactions between the pituitary, thyroid and adrenal cortex during acute exposure to cold or to electric shocks in the rat. In intact rats acclimated to 25 +/- 1 degrees C, acute exposure to cold resulted in simultaneous stimulation of TSH and ACTH secretion. The plasma TSH response to cold was identical at temperatures varying from +14 to -10 degrees C, whereas the adrenocortical response increased proportionally to the severity of cold. Acute stimulation of ACTH secretion by exposure to a stressful situation (electrical shocks) did not alter the TSH response to cold. Conversely, acute blockade of the pituitary-adrenocortical response by dexamethasone treatment did not enhance the TSH response to cold. Chronic stimulation of ACTH secretion resulting from adrenalectomy did not interfere with the TSH response during subsequent exposure to cold. However, a reduced adrenocortical response to cold was observed during chronic hypersecretion of TSH resulting from previous thyroidectomy. These findings do not support the hypothesis of an inverse relationship between TSH and ACTH secretions during acute cold exposure, but rather suggest that these secretions are independent."} {"id": "PMID:178587", "title": "Intramyofiber metastases in skeletal muscle.", "content": "Autopsy examination in a case of metastatic carcinoma revealed psoas muscle invasion with nests of tumor cells within individual myofibers. Such findings suggest that there is an intracellular route for the spread of malignant tumor in skeletal muscle.", "contents": "Intramyofiber metastases in skeletal muscle. Autopsy examination in a case of metastatic carcinoma revealed psoas muscle invasion with nests of tumor cells within individual myofibers. Such findings suggest that there is an intracellular route for the spread of malignant tumor in skeletal muscle."} {"id": "PMID:178588", "title": "Benign lymph node inclusions.", "content": "Whether obtained during a radical surgical procedure, or as the only tissue removed in various cancer staging procedures, or as incidental tissue, lymph nodes may yield pivotal histopathologic information relating to further disposition of the patient. Most important are those cases in which lymph node findings are relied upon to establish a diagnosis of malignant disease. The two cases presented here (in addition to the few reports in the literature) represent two heretofore unreported sites of occurrence of such benign inclusions. There is need for an awareness of the occurrence, benign nature, and potentially misleading associations with frequent sites of malignant change in which metastasis to regional lymph nodes is known to occur. Particularly with the growing use of mediastinoscopy the misinterpretation of such benign inclusions could prompt the insitution of incorrect and potentially hazardous therapy or a decision to withhold therapy.", "contents": "Benign lymph node inclusions. Whether obtained during a radical surgical procedure, or as the only tissue removed in various cancer staging procedures, or as incidental tissue, lymph nodes may yield pivotal histopathologic information relating to further disposition of the patient. Most important are those cases in which lymph node findings are relied upon to establish a diagnosis of malignant disease. The two cases presented here (in addition to the few reports in the literature) represent two heretofore unreported sites of occurrence of such benign inclusions. There is need for an awareness of the occurrence, benign nature, and potentially misleading associations with frequent sites of malignant change in which metastasis to regional lymph nodes is known to occur. Particularly with the growing use of mediastinoscopy the misinterpretation of such benign inclusions could prompt the insitution of incorrect and potentially hazardous therapy or a decision to withhold therapy."} {"id": "PMID:178589", "title": "Distribution of adenylate kinase and phosphoglucomutase isoenzymes in the population of the city of New York.", "content": "Blood samples from unrelated persons living in New York, N.Y., were examined for phosphoglucomutase (PGM) and adenylate kinase (AK) phenotypes, the sample consisting of 164 Caucasians, 133 Negroes, 129 persons of Spanish origin or descent, and 156 Chinese for PGM and 136 Caucasians, 134 Negroes, 136 persons of Spanish origin or descent, and 156 Chinese for AK. The PGM1 gene frequency was found to be 0.7774 for Caucasians, 0.8083 for Negroes, 0.7461 for Hispanic persons, and 0.7917 for Chinese. One Hispanic person had a very rare type, PGM 8-1-FAST. The AK1 gene frequency was found to be 0.9669 for Caucasians, 0.9813 for Negroes, 0.9779 for Hispanic persons, and 1.000 for Chinese.", "contents": "Distribution of adenylate kinase and phosphoglucomutase isoenzymes in the population of the city of New York. Blood samples from unrelated persons living in New York, N.Y., were examined for phosphoglucomutase (PGM) and adenylate kinase (AK) phenotypes, the sample consisting of 164 Caucasians, 133 Negroes, 129 persons of Spanish origin or descent, and 156 Chinese for PGM and 136 Caucasians, 134 Negroes, 136 persons of Spanish origin or descent, and 156 Chinese for AK. The PGM1 gene frequency was found to be 0.7774 for Caucasians, 0.8083 for Negroes, 0.7461 for Hispanic persons, and 0.7917 for Chinese. One Hispanic person had a very rare type, PGM 8-1-FAST. The AK1 gene frequency was found to be 0.9669 for Caucasians, 0.9813 for Negroes, 0.9779 for Hispanic persons, and 1.000 for Chinese."} {"id": "PMID:178590", "title": "Polymorphism of red cell phosphoglucomutase, adenylate kinase and adenosine deaminase in a Polish population.", "content": "Genetic variants of PGM1, AK and ADA were studied in a sample of unrelated individuals from the Polish population. The gene frequencies observed are: PGM1/1: 0.715, AK1: 0.962 AND ADA1: 0.940.", "contents": "Polymorphism of red cell phosphoglucomutase, adenylate kinase and adenosine deaminase in a Polish population. Genetic variants of PGM1, AK and ADA were studied in a sample of unrelated individuals from the Polish population. The gene frequencies observed are: PGM1/1: 0.715, AK1: 0.962 AND ADA1: 0.940."} {"id": "PMID:178591", "title": "The production of IgE and IgGa antibodies in normal rats and rats infected with Nippostrongylus brasiliensis.", "content": "The time courses of production of IgE and IgGa homocytotropic antibodies were measured in Wistar rats during a primary and secondary response to egg albumin with pertussis or Freund's adjuvants. An anamnestic IgE antibody response occurred in animals previously sensitized to antigen with killed Bordetella pertussis as adjuvant. IgGa antibodies were formed in the primary response with Freund's complete adjuvant only, but were found during the secondary response with all adjuvants used. The time courses of formation of IgE and IgGa antibodies were very different during the secondary response. The production of both classes of antibody to egg albumin was studed in Wistar and Hooded Lister rats infected with Nippostrongylus brasiliensis. IgGa antibody formation was not potentiated by the infection. However, increased levels of IgE antibody, formed during a secondary response to antigen in infected animals, were consistently higher in both strains than during a primary response.", "contents": "The production of IgE and IgGa antibodies in normal rats and rats infected with Nippostrongylus brasiliensis. The time courses of production of IgE and IgGa homocytotropic antibodies were measured in Wistar rats during a primary and secondary response to egg albumin with pertussis or Freund's adjuvants. An anamnestic IgE antibody response occurred in animals previously sensitized to antigen with killed Bordetella pertussis as adjuvant. IgGa antibodies were formed in the primary response with Freund's complete adjuvant only, but were found during the secondary response with all adjuvants used. The time courses of formation of IgE and IgGa antibodies were very different during the secondary response. The production of both classes of antibody to egg albumin was studed in Wistar and Hooded Lister rats infected with Nippostrongylus brasiliensis. IgGa antibody formation was not potentiated by the infection. However, increased levels of IgE antibody, formed during a secondary response to antigen in infected animals, were consistently higher in both strains than during a primary response."} {"id": "PMID:178595", "title": "Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression.", "content": "Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.", "contents": "Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression. Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver."} {"id": "PMID:178596", "title": "Cross-reacting herpes simplex virus antigens in hamster and mouse cells transformed by ultraviolet light-inactivated herpes simplex virus type 2.", "content": "Murine and hamster cell lines, each transformed with a different strain of herpes simplex virus (HSV), were examined for cross-reacting antigens by in vitro and in vivo assays. A comparative study by the indirect immunofluorescence technique detected common cross-reacting viral antigens. Cytoplasmic fluorescence patterns were observed in the 333-8-9 hamster line, the H238 murine line, and the H238 clonal lines; these patterns were identical to the fluorescence pattern of HSV -2-infected controls when reacted with HSV antiserum. Tumor rejection studies in the BALB/c host indicated that each cell line provided immunity against a tumorigenic challenge of transformed mouse cells. The H238 clone EC1 3 provided a 53% immunity against itself at an inoculum of 10(6); the 333-8-9 line supported a 26% immunity. These data demonstrate a common HSV antigenicity between the murine and hamster transformed lines and further indicate that the HSV genome is involved in transformation.", "contents": "Cross-reacting herpes simplex virus antigens in hamster and mouse cells transformed by ultraviolet light-inactivated herpes simplex virus type 2. Murine and hamster cell lines, each transformed with a different strain of herpes simplex virus (HSV), were examined for cross-reacting antigens by in vitro and in vivo assays. A comparative study by the indirect immunofluorescence technique detected common cross-reacting viral antigens. Cytoplasmic fluorescence patterns were observed in the 333-8-9 hamster line, the H238 murine line, and the H238 clonal lines; these patterns were identical to the fluorescence pattern of HSV -2-infected controls when reacted with HSV antiserum. Tumor rejection studies in the BALB/c host indicated that each cell line provided immunity against a tumorigenic challenge of transformed mouse cells. The H238 clone EC1 3 provided a 53% immunity against itself at an inoculum of 10(6); the 333-8-9 line supported a 26% immunity. These data demonstrate a common HSV antigenicity between the murine and hamster transformed lines and further indicate that the HSV genome is involved in transformation."} {"id": "PMID:178597", "title": "Purification of hepatitis A antigen from feces and detection of antigen and antibody by immune adherence hemagglutination.", "content": "Hepatitis A antigen (HA Ag) was purified from feces collected during acute illness from patients with naturally occurring viral hepatitis, type A. Positive fecal specimens were identified by immune electron microscopy, but for detection of HA Agduring purification immune adherence hemagglutination (IAHA) and microtiter solid-phase radioimmunoassay were used. Isopycnic banding in cesium chloride, rate-zonal separation in sucrose, and preparative zonal electrophoresis were used in various combinations for successive purification, and the purified antigen was successfully used in a test for antibody by IAHA. Seronconversions to HA Ag were demonstrated by IAHA in 20 instances of hepatitis A virus infection, but in none of six cases of type B hepatitis or three cases of post-transfusion hepatitis unrelated to heaptitis A or B viruses, nor in two individuals without hepatitis. In addition, the temporal pattern of antibody development during type A hepatitis was studied in serial sera from an experimentally infected chimpanzee. Antibody titers by IAHA correlated well with antibody ratings determined by immune electron microscopy.", "contents": "Purification of hepatitis A antigen from feces and detection of antigen and antibody by immune adherence hemagglutination. Hepatitis A antigen (HA Ag) was purified from feces collected during acute illness from patients with naturally occurring viral hepatitis, type A. Positive fecal specimens were identified by immune electron microscopy, but for detection of HA Agduring purification immune adherence hemagglutination (IAHA) and microtiter solid-phase radioimmunoassay were used. Isopycnic banding in cesium chloride, rate-zonal separation in sucrose, and preparative zonal electrophoresis were used in various combinations for successive purification, and the purified antigen was successfully used in a test for antibody by IAHA. Seronconversions to HA Ag were demonstrated by IAHA in 20 instances of hepatitis A virus infection, but in none of six cases of type B hepatitis or three cases of post-transfusion hepatitis unrelated to heaptitis A or B viruses, nor in two individuals without hepatitis. In addition, the temporal pattern of antibody development during type A hepatitis was studied in serial sera from an experimentally infected chimpanzee. Antibody titers by IAHA correlated well with antibody ratings determined by immune electron microscopy."} {"id": "PMID:178598", "title": "Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: growth characteristics and antigentic relationship.", "content": "The growth characteristics of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in cell cultures were compared. Guinea pig fibroblast cells were highly susceptible to infection with both viruses, whereas guinea pig kidney cells were sensitive only to GPHLV. No cytopathic effect was observed in the latter cell system after infection with GPCMV,nor was there an increase in virus titer, although the cirus persisted in the kidney cells for 2 to 3 weeks postinfection. Electron microscope studies showed nonvirion tubular structures in GPCMV -infected fibroblast cells, but not in GPHLV- infected cells. Large packages of enveloped nuclear virus particles were commonly seen in GPHLV -infected cells, especially kidney epithelial cells, but none were found in the GPCMV -infected fibroblasts. Complete enveloped extracellular virus particles were present in both virus-cell systems. Both viruses showed narrow host spectra and replicated well only in guinea pig cells although GPHLV multiplied to some degree in rabbit cells. No antigenic relationship could be demonstrated between the two viruses using antisera specific for each virus that was produced in rabbits and guinea pigs. Rabbits produced high neutralizing antibody titers to GPHLV, whereas guinea pigs were the animals of choice for GPCMV antiserum production.", "contents": "Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: growth characteristics and antigentic relationship. The growth characteristics of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in cell cultures were compared. Guinea pig fibroblast cells were highly susceptible to infection with both viruses, whereas guinea pig kidney cells were sensitive only to GPHLV. No cytopathic effect was observed in the latter cell system after infection with GPCMV,nor was there an increase in virus titer, although the cirus persisted in the kidney cells for 2 to 3 weeks postinfection. Electron microscope studies showed nonvirion tubular structures in GPCMV -infected fibroblast cells, but not in GPHLV- infected cells. Large packages of enveloped nuclear virus particles were commonly seen in GPHLV -infected cells, especially kidney epithelial cells, but none were found in the GPCMV -infected fibroblasts. Complete enveloped extracellular virus particles were present in both virus-cell systems. Both viruses showed narrow host spectra and replicated well only in guinea pig cells although GPHLV multiplied to some degree in rabbit cells. No antigenic relationship could be demonstrated between the two viruses using antisera specific for each virus that was produced in rabbits and guinea pigs. Rabbits produced high neutralizing antibody titers to GPHLV, whereas guinea pigs were the animals of choice for GPCMV antiserum production."} {"id": "PMID:178599", "title": "Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: pathogenesis and persistence in experimentally infected animals.", "content": "The pathogenesis of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in guinea pigs was compared. Animals were inoculated with the two viruses by different routes and sacrificed after varying periods of time. GPCMV was consistently isolated from salivary gland 2 weeks postinoculation and thereafter following intraperitoneal or subcutaneous incoulaton. Virus was less frequently found in other tissues including blood, spleen, and kidney. Intranuclear inclusions were seen in tissue sections of salivary gland after inoculation with GPCMV- infected tissue suspension, but were only rarely found after inoculation with tissue culture virus. In GPHLV-infected guinea pigs, consistent latent infection of leukocytes and other tissues was detected by cocultivation techniques. Intranuclear inclusions were not found in the spleen, salivary gland, or other infected tissues after GPHLV infection with either tissue culture virus or infected tissue suspension. Guinea pigs inoculated with GPCMV produced high titers of specific neutralizing antibody to the homologous virus; those inoculated with GPHLV developed long-term viremia accompanied by minimal neutralizing antibody levels to the virus.", "contents": "Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: pathogenesis and persistence in experimentally infected animals. The pathogenesis of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in guinea pigs was compared. Animals were inoculated with the two viruses by different routes and sacrificed after varying periods of time. GPCMV was consistently isolated from salivary gland 2 weeks postinoculation and thereafter following intraperitoneal or subcutaneous incoulaton. Virus was less frequently found in other tissues including blood, spleen, and kidney. Intranuclear inclusions were seen in tissue sections of salivary gland after inoculation with GPCMV- infected tissue suspension, but were only rarely found after inoculation with tissue culture virus. In GPHLV-infected guinea pigs, consistent latent infection of leukocytes and other tissues was detected by cocultivation techniques. Intranuclear inclusions were not found in the spleen, salivary gland, or other infected tissues after GPHLV infection with either tissue culture virus or infected tissue suspension. Guinea pigs inoculated with GPCMV produced high titers of specific neutralizing antibody to the homologous virus; those inoculated with GPHLV developed long-term viremia accompanied by minimal neutralizing antibody levels to the virus."} {"id": "PMID:178600", "title": "Attachment of Mycoplasma pneumoniae to respiratory epithelium.", "content": "The attachment of radioisotope-labeled Mycoplasma pneumoniae to hamster tracheal rings in organ culture was examined by radioautography and liquid scintillation counting. Radioautographs of individual rings exposed for 8 h to (3H) thymidine-labeled virulent M. pneumoniae revealed a dense extracellular collection of emulsion grains along the luminal surface of epithelial cells. Similar exposure of rings to isotope-labeled avirulent M. pneumoniae resulted in no accumulation of emulsion grains. The numbers of attached virulent mycoplasmas, as measured by liquid scintillation counting of infected rings, were found to increase in a nearly linear fashion over an 8-h incubation period. Viability of the mycoplasmas and metabolic integrity of the tracheal rings were important for optimal attachment. Pretreatment of rings with neuraminidase or sodium periodate significantly impaired orgainism adherence. These data suggest a specificity of interation between virulent M. pneumoniae and tracheal epithelial cells that can be further examined through the use of isotopically labeled mycoplasmas.", "contents": "Attachment of Mycoplasma pneumoniae to respiratory epithelium. The attachment of radioisotope-labeled Mycoplasma pneumoniae to hamster tracheal rings in organ culture was examined by radioautography and liquid scintillation counting. Radioautographs of individual rings exposed for 8 h to (3H) thymidine-labeled virulent M. pneumoniae revealed a dense extracellular collection of emulsion grains along the luminal surface of epithelial cells. Similar exposure of rings to isotope-labeled avirulent M. pneumoniae resulted in no accumulation of emulsion grains. The numbers of attached virulent mycoplasmas, as measured by liquid scintillation counting of infected rings, were found to increase in a nearly linear fashion over an 8-h incubation period. Viability of the mycoplasmas and metabolic integrity of the tracheal rings were important for optimal attachment. Pretreatment of rings with neuraminidase or sodium periodate significantly impaired orgainism adherence. These data suggest a specificity of interation between virulent M. pneumoniae and tracheal epithelial cells that can be further examined through the use of isotopically labeled mycoplasmas."} {"id": "PMID:178601", "title": "Effect of ambient temperatures on multiplication of attenuated transmissible gastroenteritis virus in the bodies of newborn piglets.", "content": "Newborn piglets were found to be more resistant to infection with attenuated transmissible gastroenteritis virus when maintained at higher temperatures. This was attributed to a decreased rate of virus propagation and spreading in the bodies of the infected animals. The highest virus levels were detected in the tissues of piglets maintained at 8 to 12 C. In contrast, no virus was recovered from piglets maintained at 35 to 37.5 C. The virus was found only in the lymph nodes and respiratory organs in the piglets maintained at 20 to 23 C.", "contents": "Effect of ambient temperatures on multiplication of attenuated transmissible gastroenteritis virus in the bodies of newborn piglets. Newborn piglets were found to be more resistant to infection with attenuated transmissible gastroenteritis virus when maintained at higher temperatures. This was attributed to a decreased rate of virus propagation and spreading in the bodies of the infected animals. The highest virus levels were detected in the tissues of piglets maintained at 8 to 12 C. In contrast, no virus was recovered from piglets maintained at 35 to 37.5 C. The virus was found only in the lymph nodes and respiratory organs in the piglets maintained at 20 to 23 C."} {"id": "PMID:178602", "title": "Modified hemolytic plaque technique for the detection of bluetongue virus antibody-forming cells.", "content": "A hemolytic plaque assay was developed for the detection of antibody-forming cells to bluetongue virus (BTV). Sheep erythrocytes (SRBC), onto which BTV had been absorbed, served as the indicator of lysis due to the presence of BTV antibody-forming cells. The ratio of BTV to SRBC was found to be critical for optimum hemolytic plaque formation. For routine use, 50 mul of 12% BTV SRBC, 0.1 ml of a spleen cell suspension, and 0.5 ml of 0.5% agarose in a balanced salt solution were mixed and plated on a microscope slide precoated with 0.1% aqueous agarose. Slides were incubated for 1 h at 37 C in a humidified incubator and subsequently flooded with 0.4 ml of a 1:15 dilution of complement. Incubation was continued for a further 2 h before the hemolytic plaques were scored. It was not possible to establish BTV serotype specificity by this technique.", "contents": "Modified hemolytic plaque technique for the detection of bluetongue virus antibody-forming cells. A hemolytic plaque assay was developed for the detection of antibody-forming cells to bluetongue virus (BTV). Sheep erythrocytes (SRBC), onto which BTV had been absorbed, served as the indicator of lysis due to the presence of BTV antibody-forming cells. The ratio of BTV to SRBC was found to be critical for optimum hemolytic plaque formation. For routine use, 50 mul of 12% BTV SRBC, 0.1 ml of a spleen cell suspension, and 0.5 ml of 0.5% agarose in a balanced salt solution were mixed and plated on a microscope slide precoated with 0.1% aqueous agarose. Slides were incubated for 1 h at 37 C in a humidified incubator and subsequently flooded with 0.4 ml of a 1:15 dilution of complement. Incubation was continued for a further 2 h before the hemolytic plaques were scored. It was not possible to establish BTV serotype specificity by this technique."} {"id": "PMID:178603", "title": "Counteraction of poly(4-vinylpyridine-n-oxide) on the depression of viral interferon induction by coal dust.", "content": "The depressive activity of coal dust on interferon induction by influenza was markedly subverted when either coal dust or LLC-MK2 cell monolayers were pretreated with poly (4-vinylpyridine-N-oside). The polymer alone neither induced interferon synthesis, inhibited viral induction of interferon, influenced viral multiplication, nor affected cellular-induced resistance by interferon. Absorption of the polymer to coal dust not only occurred at a more rapid rate than to cell monolayers, but also less polymer was required to pretreat coal dust than cell monolayers to achieve comparable amelioration of interferon production. The polymer effectively negated the adverse activity of coal dust particles, irrespective of the latter's size (is less than 2.0 to 74.0 mum). Virus multiplication in the presence of coal dust=treated cell monolayers attained a level that was twofol higher than that noted with either polymer-pretreated coal dust or polymer-pretreated cell monolayers. Interferon production was almost completely inhibited in the presence of coal dust; pretreating coal dust or cells with the polymer abrogated this inhibitory activity of coal dust. It is tentatively suggested that coal dust particles per se directly interact with cell membranes to subvert interferon induction and that the formation of an absorbed polymerlayer on these complexes prevents their interaction.", "contents": "Counteraction of poly(4-vinylpyridine-n-oxide) on the depression of viral interferon induction by coal dust. The depressive activity of coal dust on interferon induction by influenza was markedly subverted when either coal dust or LLC-MK2 cell monolayers were pretreated with poly (4-vinylpyridine-N-oside). The polymer alone neither induced interferon synthesis, inhibited viral induction of interferon, influenced viral multiplication, nor affected cellular-induced resistance by interferon. Absorption of the polymer to coal dust not only occurred at a more rapid rate than to cell monolayers, but also less polymer was required to pretreat coal dust than cell monolayers to achieve comparable amelioration of interferon production. The polymer effectively negated the adverse activity of coal dust particles, irrespective of the latter's size (is less than 2.0 to 74.0 mum). Virus multiplication in the presence of coal dust=treated cell monolayers attained a level that was twofol higher than that noted with either polymer-pretreated coal dust or polymer-pretreated cell monolayers. Interferon production was almost completely inhibited in the presence of coal dust; pretreating coal dust or cells with the polymer abrogated this inhibitory activity of coal dust. It is tentatively suggested that coal dust particles per se directly interact with cell membranes to subvert interferon induction and that the formation of an absorbed polymerlayer on these complexes prevents their interaction."} {"id": "PMID:178604", "title": "Inhibition by zinc of hemolysis induced by bacterial and other cytolytic agents.", "content": "Zinc, cupric, and cadmium ions, in that order of effectiveness, inhibited lysis of washed, rabbit erythrocytes by the toxic bacterial product aerolysin. Hemolysis induced by a variety of other lytic agents was also inhibited by Zn2+ in approximately the same concentration as that, 0.33 mM, needed to inhibit aerolysin-induced hemolysis. Zinc ions did not inhibit osmotic lysis. Inhibition requires the continues presence of Zn2+ and apparently involves a readily reversible binding of Zn2+ to the cell surface, which, it is postulated is accompanied by a reversible alteration in the state of the lipid bilayer.", "contents": "Inhibition by zinc of hemolysis induced by bacterial and other cytolytic agents. Zinc, cupric, and cadmium ions, in that order of effectiveness, inhibited lysis of washed, rabbit erythrocytes by the toxic bacterial product aerolysin. Hemolysis induced by a variety of other lytic agents was also inhibited by Zn2+ in approximately the same concentration as that, 0.33 mM, needed to inhibit aerolysin-induced hemolysis. Zinc ions did not inhibit osmotic lysis. Inhibition requires the continues presence of Zn2+ and apparently involves a readily reversible binding of Zn2+ to the cell surface, which, it is postulated is accompanied by a reversible alteration in the state of the lipid bilayer."} {"id": "PMID:178605", "title": "Antinuclear antibodies and elevated anti-Epstein-Barr virus titers in cancer patients.", "content": "One and one-half percent of human sera from patients seen at a clinic for treatment of cancer contained antibodies to the nuclei of chick kidney cells by indirect immunofluorescence tests. In the group of sera containing antinuclear antibodies, the geometric mean titer to Epstein-Barr virus (EBV) capsid antigen was significantly elevated. Sera obtained from normal adults or from patients with similar histological types of tumors that possessed no antinuclear antibodies contained lower levels of anti-EBV antibodies. The elevated titers to EBV were correlated with the presence or absence of antinuclear antibodies and not with a particular type or site of neoplastic disease.", "contents": "Antinuclear antibodies and elevated anti-Epstein-Barr virus titers in cancer patients. One and one-half percent of human sera from patients seen at a clinic for treatment of cancer contained antibodies to the nuclei of chick kidney cells by indirect immunofluorescence tests. In the group of sera containing antinuclear antibodies, the geometric mean titer to Epstein-Barr virus (EBV) capsid antigen was significantly elevated. Sera obtained from normal adults or from patients with similar histological types of tumors that possessed no antinuclear antibodies contained lower levels of anti-EBV antibodies. The elevated titers to EBV were correlated with the presence or absence of antinuclear antibodies and not with a particular type or site of neoplastic disease."} {"id": "PMID:178606", "title": "Temperature-dependent inactivating factor of Pseudomonas aeruginosa exotoxin A.", "content": "The adenosine diphosphate ribosyl transferase activity of Pseudomonas aeruginosa exotoxin A(PA toxin) was found to be rapidly destroyed by heating at 45 to 60C but not by heating at 70 to 90C (for at least 30 min). This phenomenon has been previously described for other bacterial toxins (staphylococcal alpha-toxin and Vibrio parahaemolyticus hemolysin) and is termed an Arrhenius effect. In contrast, the Arrhenius effect was not seen when the PA toxin was heat-treated as above and tested for cell toxicity or mouse lethality. Although the PA toxin treated at 70C for 30 min retained a significant proportion (is greater than 70%) of its adenosine diphosphate ribosyl transferase activity, the cell toxicity and mouse lethality of the toxin were virtually abolished. A temperature-dependent inactivating factor that has proteolytic activity and is co-purified with the PA toxin was shown to be responsible for the Arrhenius effect. PA toxin separated from the factor by conventional disc gel electrophoresis or PA toxin preparations lacking the factor did not show the Arrhenius effect.", "contents": "Temperature-dependent inactivating factor of Pseudomonas aeruginosa exotoxin A. The adenosine diphosphate ribosyl transferase activity of Pseudomonas aeruginosa exotoxin A(PA toxin) was found to be rapidly destroyed by heating at 45 to 60C but not by heating at 70 to 90C (for at least 30 min). This phenomenon has been previously described for other bacterial toxins (staphylococcal alpha-toxin and Vibrio parahaemolyticus hemolysin) and is termed an Arrhenius effect. In contrast, the Arrhenius effect was not seen when the PA toxin was heat-treated as above and tested for cell toxicity or mouse lethality. Although the PA toxin treated at 70C for 30 min retained a significant proportion (is greater than 70%) of its adenosine diphosphate ribosyl transferase activity, the cell toxicity and mouse lethality of the toxin were virtually abolished. A temperature-dependent inactivating factor that has proteolytic activity and is co-purified with the PA toxin was shown to be responsible for the Arrhenius effect. PA toxin separated from the factor by conventional disc gel electrophoresis or PA toxin preparations lacking the factor did not show the Arrhenius effect."} {"id": "PMID:178607", "title": "Pathogenesis of Sendai virus infection in the central nervous system of mice.", "content": "The present study was aimed to clarify the pathogenesis of Sendai virus infection to the central nervous system (CNS) of mice. One-to 2-day-old suckling and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied higher in suclings than in adults. Immunofluorescent studies in sucklings revealed that the viral antigens appeared initially in ependyma, choroid plexus epithelium, and meninges. Subsequently they spread to subependymal cells and finally were found in neurons of hippocampus for as long as 4 months postinfection. In adults, however, the viral antigens rapidly disappeared in the early stage. Most mice inoculated intracerebrally with Sendai virus appeared healthy, although hydropcephalus developed in a few mice. Virus-specific antibody and interferon production seemed to have no influence on the persistent infection of Sendai virus in the CNS of mice. One of the most significant findings may be that the viral antigens persist in the brain for as long as 4 months in a latent form. This may offer a useful model for the study of latent CNS infection of paramyxoviruses.", "contents": "Pathogenesis of Sendai virus infection in the central nervous system of mice. The present study was aimed to clarify the pathogenesis of Sendai virus infection to the central nervous system (CNS) of mice. One-to 2-day-old suckling and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied higher in suclings than in adults. Immunofluorescent studies in sucklings revealed that the viral antigens appeared initially in ependyma, choroid plexus epithelium, and meninges. Subsequently they spread to subependymal cells and finally were found in neurons of hippocampus for as long as 4 months postinfection. In adults, however, the viral antigens rapidly disappeared in the early stage. Most mice inoculated intracerebrally with Sendai virus appeared healthy, although hydropcephalus developed in a few mice. Virus-specific antibody and interferon production seemed to have no influence on the persistent infection of Sendai virus in the CNS of mice. One of the most significant findings may be that the viral antigens persist in the brain for as long as 4 months in a latent form. This may offer a useful model for the study of latent CNS infection of paramyxoviruses."} {"id": "PMID:178608", "title": "Quantitative cytophotometry evaluated as a method for analyses of herpes simplex viral deoxyribonucleic acid synthesis.", "content": "Feulgen deoxyribonucleic acid (F-DNA) microspectrophotometry was evaluated as a potential tool for quantification of herpes simplex virus type 1 (HSV-1) and 2(HSV-2) DNA synthesis in single cells. Since HSV DNA synthesis has been extensively studied using incorporation of radioactive precursors into viral and cellular DNA, microspectrophotometric measures were correlated with biochemical data obtained using tritium-labeled thymidine ([3H]TdR). It was established that: (i) viral-induced increaae in F-DNA can be cytophotometrically detected between 1 and 6 h postinjection (p.i.), which corresponds to the initial incorporation of [3H) TdR into viral DNA; (ii) peak F-DNA levels occurred 8 h p.i., which supported cytological observations of a more rapid development of an inclusion body in HSV-2-infected nuclei. Despite the fact that F-DNA cytophotometry is unable to distinguish between cell and viral DNA, the overall study supports the existence of a good correlation between data obtained using microspectrophotometric and conventional isotope methods. Furthermore, cytophotometry complements biochemical evaluations in that it permits analyses of DNA changes on a single-cell basis or the detection of infection in very small numbers of cells.", "contents": "Quantitative cytophotometry evaluated as a method for analyses of herpes simplex viral deoxyribonucleic acid synthesis. Feulgen deoxyribonucleic acid (F-DNA) microspectrophotometry was evaluated as a potential tool for quantification of herpes simplex virus type 1 (HSV-1) and 2(HSV-2) DNA synthesis in single cells. Since HSV DNA synthesis has been extensively studied using incorporation of radioactive precursors into viral and cellular DNA, microspectrophotometric measures were correlated with biochemical data obtained using tritium-labeled thymidine ([3H]TdR). It was established that: (i) viral-induced increaae in F-DNA can be cytophotometrically detected between 1 and 6 h postinjection (p.i.), which corresponds to the initial incorporation of [3H) TdR into viral DNA; (ii) peak F-DNA levels occurred 8 h p.i., which supported cytological observations of a more rapid development of an inclusion body in HSV-2-infected nuclei. Despite the fact that F-DNA cytophotometry is unable to distinguish between cell and viral DNA, the overall study supports the existence of a good correlation between data obtained using microspectrophotometric and conventional isotope methods. Furthermore, cytophotometry complements biochemical evaluations in that it permits analyses of DNA changes on a single-cell basis or the detection of infection in very small numbers of cells."} {"id": "PMID:178609", "title": "Efficacy of phosphonoacetic acid on herpes simplex virus infection of sensory ganglia.", "content": "Treatment of mice with phosphonoacetic acid markedly reduced the incidence of latent ganglionic infection with herpes simplex virus when administered within 24 h after viral inoculation, but had no effect on an already established ganglionic infection.", "contents": "Efficacy of phosphonoacetic acid on herpes simplex virus infection of sensory ganglia. Treatment of mice with phosphonoacetic acid markedly reduced the incidence of latent ganglionic infection with herpes simplex virus when administered within 24 h after viral inoculation, but had no effect on an already established ganglionic infection."} {"id": "PMID:178610", "title": "Tumour angiogenesis factor (TAF) in human and animal tumours.", "content": "Extracts were made from Walker 256 carcinoma, spontaneous rat mammary adenocarcinoma, Wilms' tumour, human neuroblastoma and human haemangioma. Chromatography of the extracts on Sephadex G-100 yielded four fractions, A, B, C and D. Injection of fractions B and C resulted in the growth of new capillaries in the subcutaneous fascia or rats. Controls, e.g. similar extracts of rat liver or human kidney, did not induce neovascularisation. The endothelium of newly-formed blood vessels contained many mitotic figures. A limitation of this method is that it is qualitative only. In order to develop a quantitative in vitro assay for a tumour angiogenesis factor (TAF), short-term primary cultures were initiated from adult rat brain white matter, as cells from such cultures were shown to be vascular in origin. Addition of fractions containing TAF (B and C) which were active in vivo failed to stimulate thymidine uptake by the cells. The possible reasons for this failure and the therapeutic potential of TAF in cancer control are discussed.", "contents": "Tumour angiogenesis factor (TAF) in human and animal tumours. Extracts were made from Walker 256 carcinoma, spontaneous rat mammary adenocarcinoma, Wilms' tumour, human neuroblastoma and human haemangioma. Chromatography of the extracts on Sephadex G-100 yielded four fractions, A, B, C and D. Injection of fractions B and C resulted in the growth of new capillaries in the subcutaneous fascia or rats. Controls, e.g. similar extracts of rat liver or human kidney, did not induce neovascularisation. The endothelium of newly-formed blood vessels contained many mitotic figures. A limitation of this method is that it is qualitative only. In order to develop a quantitative in vitro assay for a tumour angiogenesis factor (TAF), short-term primary cultures were initiated from adult rat brain white matter, as cells from such cultures were shown to be vascular in origin. Addition of fractions containing TAF (B and C) which were active in vivo failed to stimulate thymidine uptake by the cells. The possible reasons for this failure and the therapeutic potential of TAF in cancer control are discussed."} {"id": "PMID:178611", "title": "Establishment and characterization of a human histiocytic lymphoma cell line (U-937).", "content": "A human hematopoietic cell line (U-937) with exceptional characteristics was derived from a patient with generalized histiocytic lymphoma. The morphology of the cell line was identical to that of the tumor cells in the pleural effusion from which the line was derived. Since Epstein-Barr virus (EBV) carrying diploid lymphoblastoid cell lines unrelated to the tumor population often become established in vitro from non-Burkitt lymphoma explants, several parameters were studied to discriminate the U-937 from such lines: morphology in vitro, growth characteristics, cytochemistry, surface receptor pattern, Ig production, lysozyme production, beta2-microglobulin production, presence of EBV genome and karyotype. In all these respects U-937 differed from prototype lymphoblastoid cell lines. The histiocytic origin of the cell line was shown by its capacity for lysozyme production and the strong esterase activity (naphtol AS-D acetate esterase inhibited by NaF) of the cells. It is therefore concluded that the U-937 is a neoplastic, histiocytic cell line.", "contents": "Establishment and characterization of a human histiocytic lymphoma cell line (U-937). A human hematopoietic cell line (U-937) with exceptional characteristics was derived from a patient with generalized histiocytic lymphoma. The morphology of the cell line was identical to that of the tumor cells in the pleural effusion from which the line was derived. Since Epstein-Barr virus (EBV) carrying diploid lymphoblastoid cell lines unrelated to the tumor population often become established in vitro from non-Burkitt lymphoma explants, several parameters were studied to discriminate the U-937 from such lines: morphology in vitro, growth characteristics, cytochemistry, surface receptor pattern, Ig production, lysozyme production, beta2-microglobulin production, presence of EBV genome and karyotype. In all these respects U-937 differed from prototype lymphoblastoid cell lines. The histiocytic origin of the cell line was shown by its capacity for lysozyme production and the strong esterase activity (naphtol AS-D acetate esterase inhibited by NaF) of the cells. It is therefore concluded that the U-937 is a neoplastic, histiocytic cell line."} {"id": "PMID:178612", "title": "Activation in vitro by BUdR of a productive EB virus infection in the epithelial cells of nasopharyngeal carcinoma.", "content": "Material from a nasopharyngeal carcinoma (NCP) has been passaged in athymic (nude) mice to eliminate non-malignant infiltrating cells. The human origin and derivation from NPC malignant epithelial cells of the nude mouse tumours have been confirmed by chromosome examination, electron microscopy showing desmosomes and keratin fibrils, and postive EB virus nuclear antigen (EBNA) testing. Samples of the mouse-grown tumours were cultured and pure monolayers of epithelial cells were obtained which still expressed EBNA and contained desmosomes and keratin; these cultures grew well for about 3 weeks. Extensive electron microscope searches failed to reveal herpes virus particles. In contrast, cultures treated with BUdR showed typical immature and mature herpes virus particles in epithelial, keratin-containing cells, and immunofluorescence tests for virus capsid antigen with a battery of human sera identified this agent as EB virus. EB virus has thus, for the first time, been activated in NPC epithelial cells and shown to be capable of replication in a cell type other than a primate B-lymphocyte.", "contents": "Activation in vitro by BUdR of a productive EB virus infection in the epithelial cells of nasopharyngeal carcinoma. Material from a nasopharyngeal carcinoma (NCP) has been passaged in athymic (nude) mice to eliminate non-malignant infiltrating cells. The human origin and derivation from NPC malignant epithelial cells of the nude mouse tumours have been confirmed by chromosome examination, electron microscopy showing desmosomes and keratin fibrils, and postive EB virus nuclear antigen (EBNA) testing. Samples of the mouse-grown tumours were cultured and pure monolayers of epithelial cells were obtained which still expressed EBNA and contained desmosomes and keratin; these cultures grew well for about 3 weeks. Extensive electron microscope searches failed to reveal herpes virus particles. In contrast, cultures treated with BUdR showed typical immature and mature herpes virus particles in epithelial, keratin-containing cells, and immunofluorescence tests for virus capsid antigen with a battery of human sera identified this agent as EB virus. EB virus has thus, for the first time, been activated in NPC epithelial cells and shown to be capable of replication in a cell type other than a primate B-lymphocyte."} {"id": "PMID:178613", "title": "Localization of mouse satellite DNA on chromosomes of experimentally induced glioblastomas; non-centromeric lable in one glioblastoma producing C-type particles.", "content": "The chromosomal localization of satellite DNA in two tissue culture lines derived -rom malignant mouse CNS tumors was investigated by in situ hybridization of 3H single-stranded satellite DNA purified by isopynic centrifugation in alkaline CSC1. Both tumors were glioblastomas originally induced by a methylcholanthrene implantation into the cerebrum of C3H mice; both displayed aneuploid chromosomal constitutions. One of these glioblastomas (TC 541) revealed labelling only of centromeric portions of the chromosomes even in cells containing greater than 200 chromosomes and thus it had a pattern of satellite distribution comparable to that of normal cells. The other glioblastoma (TC 509), that produced C-type particles and had a decrease in satellite DNA, displayed interstitial and telomeric label in some chromosomes in addition to labelling of the centromeres. \"Hoechst 33258\" fluorescence showed some interstitial and telomeric bright bands as well as centromeric bright regions, though to be consistent with in situ studies. The localization of satellite DNA to the chromosome arms and its possible relation to C-type virus is discussed.", "contents": "Localization of mouse satellite DNA on chromosomes of experimentally induced glioblastomas; non-centromeric lable in one glioblastoma producing C-type particles. The chromosomal localization of satellite DNA in two tissue culture lines derived -rom malignant mouse CNS tumors was investigated by in situ hybridization of 3H single-stranded satellite DNA purified by isopynic centrifugation in alkaline CSC1. Both tumors were glioblastomas originally induced by a methylcholanthrene implantation into the cerebrum of C3H mice; both displayed aneuploid chromosomal constitutions. One of these glioblastomas (TC 541) revealed labelling only of centromeric portions of the chromosomes even in cells containing greater than 200 chromosomes and thus it had a pattern of satellite distribution comparable to that of normal cells. The other glioblastoma (TC 509), that produced C-type particles and had a decrease in satellite DNA, displayed interstitial and telomeric label in some chromosomes in addition to labelling of the centromeres. \"Hoechst 33258\" fluorescence showed some interstitial and telomeric bright bands as well as centromeric bright regions, though to be consistent with in situ studies. The localization of satellite DNA to the chromosome arms and its possible relation to C-type virus is discussed."} {"id": "PMID:178615", "title": "The effect of calcium chloride on the activity and inhibition of bacterial collagenase.", "content": "The enzymatic behavior and inhibition patterns of collagenase of Clostridium histolyticum in the presence of 0.5 M and 3.4 mM CaCl2 have been examined viscosimetrically. The more concentrated salt was found to enhance the rate of digestion of calfskin collagen when either measured viscosimetrically or colorimetrically by trinitrobenzenesulfonate. However, the rate of digestion of calfskin gelatin is unaffected by 0.5 M CaCl2 as determined colorimetrically. Calcium chloride also proved to have a marked effect on the inhibitory behavior of a series of imidazole compounds. Histidine (10mM) is about three-fold more effective as an inhibitor in 0.5 M CaCl2 than in 3.4 mM CaCl2, whereas a reverse effect is true for histamine, Imidazolylpropionate (10mM) was only weakly inhibitory (16%) in 0.5 M CaCl2 and not at all in 3.4 mM CaCl2. Inhibition by 10 mM imidazole was not detectable. These observations may be useful in the design of inhibitors for tissue collagenases which share a number of common characteristics with the bacterial enzyme.", "contents": "The effect of calcium chloride on the activity and inhibition of bacterial collagenase. The enzymatic behavior and inhibition patterns of collagenase of Clostridium histolyticum in the presence of 0.5 M and 3.4 mM CaCl2 have been examined viscosimetrically. The more concentrated salt was found to enhance the rate of digestion of calfskin collagen when either measured viscosimetrically or colorimetrically by trinitrobenzenesulfonate. However, the rate of digestion of calfskin gelatin is unaffected by 0.5 M CaCl2 as determined colorimetrically. Calcium chloride also proved to have a marked effect on the inhibitory behavior of a series of imidazole compounds. Histidine (10mM) is about three-fold more effective as an inhibitor in 0.5 M CaCl2 than in 3.4 mM CaCl2, whereas a reverse effect is true for histamine, Imidazolylpropionate (10mM) was only weakly inhibitory (16%) in 0.5 M CaCl2 and not at all in 3.4 mM CaCl2. Inhibition by 10 mM imidazole was not detectable. These observations may be useful in the design of inhibitors for tissue collagenases which share a number of common characteristics with the bacterial enzyme."} {"id": "PMID:178622", "title": "Immunology of herpes simplex virus in fection.", "content": "The accompanying inflammation seen in ocular HSV infection-the result of interactions between viruses and the immune response-can be both beneficial and potentially harmful to the host. An understanding of the interaction of virus-immune cells is just evolving from current advances in basic research. Based on our studies on HSV keratitis [11], the control of ocular HSV infection appears to involve an early inflammatory phase with macrophage reactivity and elaboration of MIF. Transient virus-specific lymphocytes with effector reactivity, as well as neutrophils with chemotactic activity, occur during the stromal keratitis. Finally, antibody-dependent complement-mediated lysis provides another phase of restriction of infection. Thus, a rationale for effective management and therapy of occular HSV disease must be based on an understanding of (1) the immunological and immunopathological mechanisms of corneal inflammatory disease initiated by the virus; (2) the immunological mechanisms in recovery from the disease; and (3) the host's humoral and cellular immune status during virus persistence (latency) and during recurrent episodes of infection. We hope that new information obtained from assessment of roles of the humoral and cellular immune responses in recovery from disease and in recurrent disease will provide new approaches to the management of ocular HSV infections.", "contents": "Immunology of herpes simplex virus in fection. The accompanying inflammation seen in ocular HSV infection-the result of interactions between viruses and the immune response-can be both beneficial and potentially harmful to the host. An understanding of the interaction of virus-immune cells is just evolving from current advances in basic research. Based on our studies on HSV keratitis [11], the control of ocular HSV infection appears to involve an early inflammatory phase with macrophage reactivity and elaboration of MIF. Transient virus-specific lymphocytes with effector reactivity, as well as neutrophils with chemotactic activity, occur during the stromal keratitis. Finally, antibody-dependent complement-mediated lysis provides another phase of restriction of infection. Thus, a rationale for effective management and therapy of occular HSV disease must be based on an understanding of (1) the immunological and immunopathological mechanisms of corneal inflammatory disease initiated by the virus; (2) the immunological mechanisms in recovery from the disease; and (3) the host's humoral and cellular immune status during virus persistence (latency) and during recurrent episodes of infection. We hope that new information obtained from assessment of roles of the humoral and cellular immune responses in recovery from disease and in recurrent disease will provide new approaches to the management of ocular HSV infections."} {"id": "PMID:178623", "title": "Localization of the major group-specific protein (p27) of avian tumor viruses by immunofluorescence in chicken cells and tissues.", "content": "An immunofluorescence technique was developed for the major group-specific (gs) p27 antigen of avian type C viruses. The localization of this antigen virus-infected in chick embryo fibroblasts was perinuclear, intracytoplasmic and at the cell surface in the majority of the cells, while it was at the cell surface only in some of the cells. No antigen was found in the nucleus. When chickens were experimentally infected with RAV-1 or a wild-strain avian leukosis virus (of subgroup A), the viral gs antigen was detected in lymphocytes of bursa of Fabricius and the spleen. Distinct specific staining was seen in the medulla of germinal centers in bursas of Fabricius and in the white pulp of the spleen where B lymphocytes are thought to be located. This is consistent with the possibility that B lymphocytes are the target cells in the infection of chickens with avian leukemia viruses.", "contents": "Localization of the major group-specific protein (p27) of avian tumor viruses by immunofluorescence in chicken cells and tissues. An immunofluorescence technique was developed for the major group-specific (gs) p27 antigen of avian type C viruses. The localization of this antigen virus-infected in chick embryo fibroblasts was perinuclear, intracytoplasmic and at the cell surface in the majority of the cells, while it was at the cell surface only in some of the cells. No antigen was found in the nucleus. When chickens were experimentally infected with RAV-1 or a wild-strain avian leukosis virus (of subgroup A), the viral gs antigen was detected in lymphocytes of bursa of Fabricius and the spleen. Distinct specific staining was seen in the medulla of germinal centers in bursas of Fabricius and in the white pulp of the spleen where B lymphocytes are thought to be located. This is consistent with the possibility that B lymphocytes are the target cells in the infection of chickens with avian leukemia viruses."} {"id": "PMID:178624", "title": "Cytomegalovirus: nucleocapsid assembly and core structure.", "content": "New ultrastructual aspects of cytomegalovirus nucleocapsid assembly are illustrated in cells from a Kaposi sarcoma. The occurrence of viral deoxyribonucleoproteins in the form of strands and penetration of these strands into open capsids is illustrated. The geometrical arrangement of the core material of the nucleocapsid is aslo emphasized.", "contents": "Cytomegalovirus: nucleocapsid assembly and core structure. New ultrastructual aspects of cytomegalovirus nucleocapsid assembly are illustrated in cells from a Kaposi sarcoma. The occurrence of viral deoxyribonucleoproteins in the form of strands and penetration of these strands into open capsids is illustrated. The geometrical arrangement of the core material of the nucleocapsid is aslo emphasized."} {"id": "PMID:178625", "title": "The induction of SV40-transformed chinese hamster and mouse kidney cells by mitomycin C.", "content": "The induction by mitomycin C (MC) of SV40 production in three lines of semi- or nonpermissive SV40-transformed cells is described. The production of virions by a line of semipermissive, virus-shedding Chinese hamster kidney cells is increased 1,000-fold by MC treatment; the proportion of infectious centers and V-antigen-containing cells is increased to a lesser degree, suggesting that both the burst per cell and the number of virus-producing cells are increased. MC treatment induces the production of small amounts of infectious DNA and virions in one line of nonpermissive mouse kidney cells, and infectious DNA apparently alone in another.", "contents": "The induction of SV40-transformed chinese hamster and mouse kidney cells by mitomycin C. The induction by mitomycin C (MC) of SV40 production in three lines of semi- or nonpermissive SV40-transformed cells is described. The production of virions by a line of semipermissive, virus-shedding Chinese hamster kidney cells is increased 1,000-fold by MC treatment; the proportion of infectious centers and V-antigen-containing cells is increased to a lesser degree, suggesting that both the burst per cell and the number of virus-producing cells are increased. MC treatment induces the production of small amounts of infectious DNA and virions in one line of nonpermissive mouse kidney cells, and infectious DNA apparently alone in another."} {"id": "PMID:178629", "title": "[Sturcture and morphogenesis of xanthomas in hyperlipoproteinemia type III. A morphologic, histochemical and electron microscopy study].", "content": "Histological, histochemical and electron-microscopical examinations have been performed on xanthoma of the skin and palmar creases in 5 patients with hyperlipoproteinemia type III, to follow the dynamics of xanthoma formation. The results were as follows: 1. There are no basic differences in histomorphology between xanthomas in type III-HLP and other types of HLP. Typical findings are: Rather dense distribution of relatively small foam cells within the dermis, only a few foam giant cells, great amounts of cholesterol intra- and extracellulary, and circumscribed necrobioses. 2. Xanthoma formation in type III-HLP is induced by pathological plasma lipoproteins. These seem to pass the endothelial barrier via pinocytosis or/and filtration. Between endothelial cells and their basal lamina plasma components sometimes could be observed. 3. The pathological lipoproteins induce a phagocytic reaction with foam cell formation in the dermal tissue. At first an augmentation of lymphocytoid or histiocytoid tissue macrophages could be detected in the dermis and especially in the perivascular region of venous blood vessels in the middermis. Perithelial cells as well as lymphocytoid and histiocytoid tissue macrophages engulve lipoproteins. Cytoplasmic enrichment of vacuoles with an electron opaque content (lipoproteins) are typical for type III-HLP; they lead to formation of typical foam cells. Within those cells lysosomal intracellular degradation of the engulved lipoproteins takes place; free cholesterol cristals, phospholipid-containing myelinic figures and residual bodies are endproducts of this process. They can lead to cellular necrosis with cellular remnants, lipoprotein vacuoles, free cholesterol and phospholipids lying free within the dermal tissue. 4. Factors are not well understood which control circumscribed xanthoma formation in type III-HLP. 5. These investigations show, that xanthomas are reactive new formations. The leading cellular substrate is the tissue macrophage, which is transformed into a foam cell by intake of lipoproteins. Foam cell formation, however, is not the result of a simple process of storage: after lipoprotein intake numerous, to a part lysosomal processes of chemical degradation and transformation, take place with an appearance of intracellular endproducts (free cholesterol, residual bodies, phospholipid-containing membranes). It is suggested that the dynamics of xanthoma formation might be importance in understanding of the process of atherosclerosis in those patients.", "contents": "[Sturcture and morphogenesis of xanthomas in hyperlipoproteinemia type III. A morphologic, histochemical and electron microscopy study]. Histological, histochemical and electron-microscopical examinations have been performed on xanthoma of the skin and palmar creases in 5 patients with hyperlipoproteinemia type III, to follow the dynamics of xanthoma formation. The results were as follows: 1. There are no basic differences in histomorphology between xanthomas in type III-HLP and other types of HLP. Typical findings are: Rather dense distribution of relatively small foam cells within the dermis, only a few foam giant cells, great amounts of cholesterol intra- and extracellulary, and circumscribed necrobioses. 2. Xanthoma formation in type III-HLP is induced by pathological plasma lipoproteins. These seem to pass the endothelial barrier via pinocytosis or/and filtration. Between endothelial cells and their basal lamina plasma components sometimes could be observed. 3. The pathological lipoproteins induce a phagocytic reaction with foam cell formation in the dermal tissue. At first an augmentation of lymphocytoid or histiocytoid tissue macrophages could be detected in the dermis and especially in the perivascular region of venous blood vessels in the middermis. Perithelial cells as well as lymphocytoid and histiocytoid tissue macrophages engulve lipoproteins. Cytoplasmic enrichment of vacuoles with an electron opaque content (lipoproteins) are typical for type III-HLP; they lead to formation of typical foam cells. Within those cells lysosomal intracellular degradation of the engulved lipoproteins takes place; free cholesterol cristals, phospholipid-containing myelinic figures and residual bodies are endproducts of this process. They can lead to cellular necrosis with cellular remnants, lipoprotein vacuoles, free cholesterol and phospholipids lying free within the dermal tissue. 4. Factors are not well understood which control circumscribed xanthoma formation in type III-HLP. 5. These investigations show, that xanthomas are reactive new formations. The leading cellular substrate is the tissue macrophage, which is transformed into a foam cell by intake of lipoproteins. Foam cell formation, however, is not the result of a simple process of storage: after lipoprotein intake numerous, to a part lysosomal processes of chemical degradation and transformation, take place with an appearance of intracellular endproducts (free cholesterol, residual bodies, phospholipid-containing membranes). It is suggested that the dynamics of xanthoma formation might be importance in understanding of the process of atherosclerosis in those patients."} {"id": "PMID:178630", "title": "Comparative sensitivity of the BGM cell line for isolation of enteric viruses.", "content": "The BGM line of African green monkey kidney cells was less sensitive than primary rhesus monkey kidney cells or human fetal diploid kidney cells for isolation of certain echoviruses and adenoviruses from fecal specimens.", "contents": "Comparative sensitivity of the BGM cell line for isolation of enteric viruses. The BGM line of African green monkey kidney cells was less sensitive than primary rhesus monkey kidney cells or human fetal diploid kidney cells for isolation of certain echoviruses and adenoviruses from fecal specimens."} {"id": "PMID:178626", "title": "Fucolipid patterns of cell lines transformed by highly and weakly tumorigenic simian virus 40 and herpes simplex virus.", "content": "The fucolipids of simian virus 40 (SV40)-transformed Balb/c mouse and herpes simplex virus (HSV)-transformed hamster cells of varying degrees of tumorigenicity were examined. In the virus-transformed cell lines and in a spontaneously transformed cell line, as compared to non-transformed cell lines, there was a decrease in the incorporation of fucose radioactivity into fucolipid IV. Fucolipid IV is the least chromatographically mobile, presumably most complex fucolipid. Only in the highly transplantable SV40- and HSV-transformed cell lines was the decrease in incorporation of radioactivity in fucolipid IV as marked as that observed in oncornavirus-transformed cell lines. Similarly, only in the highly tumorigenic DNA-virus-transformed cell lines was there a significant increase in incorporation of radioactivity from radioisotopically-labeled fucose into fucolipid III as has been observed in oncornavirus-transformed cell lines.", "contents": "Fucolipid patterns of cell lines transformed by highly and weakly tumorigenic simian virus 40 and herpes simplex virus. The fucolipids of simian virus 40 (SV40)-transformed Balb/c mouse and herpes simplex virus (HSV)-transformed hamster cells of varying degrees of tumorigenicity were examined. In the virus-transformed cell lines and in a spontaneously transformed cell line, as compared to non-transformed cell lines, there was a decrease in the incorporation of fucose radioactivity into fucolipid IV. Fucolipid IV is the least chromatographically mobile, presumably most complex fucolipid. Only in the highly transplantable SV40- and HSV-transformed cell lines was the decrease in incorporation of radioactivity in fucolipid IV as marked as that observed in oncornavirus-transformed cell lines. Similarly, only in the highly tumorigenic DNA-virus-transformed cell lines was there a significant increase in incorporation of radioactivity from radioisotopically-labeled fucose into fucolipid III as has been observed in oncornavirus-transformed cell lines."} {"id": "PMID:178627", "title": "Cross-protection between Tacaribe complex viruses. Presence of neutralizing antibodies against Junin virus (Argentine hemorrhagic fever) in guinea pigs infected with Tacaribe virus.", "content": "Cross-protection between Junin virus and five other Tacaribe complex viruses and the serological response of guinea pigs inoculated with Tacaribe virus are reported here. Previous infection with Tamiami or Pichinde viruses significantly delayed guinea pig deaths. A 58% survival rate was found among animals immunized with three doses of Amapari virus, while guinea pigs inoculated with one dose of Machupo or Tacaribe virus were fully protected against Junin virus. Neutralization tests performed in serum samples of guinea pigs immunized with five doses of Tacaribe virus showed that they developed monologous and heterologous neutralizing antibodies.", "contents": "Cross-protection between Tacaribe complex viruses. Presence of neutralizing antibodies against Junin virus (Argentine hemorrhagic fever) in guinea pigs infected with Tacaribe virus. Cross-protection between Junin virus and five other Tacaribe complex viruses and the serological response of guinea pigs inoculated with Tacaribe virus are reported here. Previous infection with Tamiami or Pichinde viruses significantly delayed guinea pig deaths. A 58% survival rate was found among animals immunized with three doses of Amapari virus, while guinea pigs inoculated with one dose of Machupo or Tacaribe virus were fully protected against Junin virus. Neutralization tests performed in serum samples of guinea pigs immunized with five doses of Tacaribe virus showed that they developed monologous and heterologous neutralizing antibodies."} {"id": "PMID:178628", "title": "A major difference in the strategy of the calici- and picornaviruses and its significance in classification.", "content": "Pig kidney (1BRS-2) cells infected with vesicular exanthema virus (VEV), a calicivirus, did not contain any large precursor polypeptides similar to those found when they were infected with foot-and-mouth disease virus (FMDV). The largest induced protein found in the VEV-infected cells had a molecular weight identical with that of the virus structural polypeptide. This difference in strategy between VEV and FMDV, taken in conjunction with the morphological and structural differences described previously, provides strong evidence that the caliciviruses should not be included in the family Picornaviridae.", "contents": "A major difference in the strategy of the calici- and picornaviruses and its significance in classification. Pig kidney (1BRS-2) cells infected with vesicular exanthema virus (VEV), a calicivirus, did not contain any large precursor polypeptides similar to those found when they were infected with foot-and-mouth disease virus (FMDV). The largest induced protein found in the VEV-infected cells had a molecular weight identical with that of the virus structural polypeptide. This difference in strategy between VEV and FMDV, taken in conjunction with the morphological and structural differences described previously, provides strong evidence that the caliciviruses should not be included in the family Picornaviridae."} {"id": "PMID:178634", "title": "Soluble proteins and hydrolases during crown-gall induction in the tomato, Lycopersicon esculentum.", "content": "Soluble proteins isolated from tissues of the tomato Lycopersicon esculentum, after inoculation with Agrobacterium tumefaciens to induce tumours, have been examined by gel electrophoresis and cytochemically. Changes that occur include the suppression of host enzymes, the appearance of bacterial enzymes in the host tissues and the appearance of new enzyme bands in the affected cells. These changes are detectable within 6 hr of infection and prior to evident morphological changes, and may be explained as derepression and repression of host genes, or the expression of released bacterial genes in the host cells.", "contents": "Soluble proteins and hydrolases during crown-gall induction in the tomato, Lycopersicon esculentum. Soluble proteins isolated from tissues of the tomato Lycopersicon esculentum, after inoculation with Agrobacterium tumefaciens to induce tumours, have been examined by gel electrophoresis and cytochemically. Changes that occur include the suppression of host enzymes, the appearance of bacterial enzymes in the host tissues and the appearance of new enzyme bands in the affected cells. These changes are detectable within 6 hr of infection and prior to evident morphological changes, and may be explained as derepression and repression of host genes, or the expression of released bacterial genes in the host cells."} {"id": "PMID:178635", "title": "Stabilization of configurational states and enzyme activities in subcellular fractions after fixation with extremely low concentrations of glutaraldehyde.", "content": "The activities of various enzymes in some subcellular organelle fractions were examined after fixation in glutaraldehyde of various concentrations. A high speed centrifuge was used to shorten the fixation time. At the lowest concentration (0.01%) glutaraldehyde stabilized instable configurational states of mitochondria as revealed by electron microscopy. In addition, at this concentration, at least 70% of the original monoamine oxidase, ATPase and cytochrome oxidase activities were preserved. The activity of acid phosphatase, on the other hand, was enhanced in a lysosomal fraction when fixed with the aldehyde at higher concentrations, e.g. 0.1% and 1.0%. It is possible that the aldehyde at higher concentrations has the same effects on the lysosomal membrane as freeze-thawing. Glucose-6-phosphatase activity was well-preserved in a microsomal fraction fixed with 0.01% glutaraldehyde but was decreased drastically when the concentration of the aldehyde was greater than 0.05%.", "contents": "Stabilization of configurational states and enzyme activities in subcellular fractions after fixation with extremely low concentrations of glutaraldehyde. The activities of various enzymes in some subcellular organelle fractions were examined after fixation in glutaraldehyde of various concentrations. A high speed centrifuge was used to shorten the fixation time. At the lowest concentration (0.01%) glutaraldehyde stabilized instable configurational states of mitochondria as revealed by electron microscopy. In addition, at this concentration, at least 70% of the original monoamine oxidase, ATPase and cytochrome oxidase activities were preserved. The activity of acid phosphatase, on the other hand, was enhanced in a lysosomal fraction when fixed with the aldehyde at higher concentrations, e.g. 0.1% and 1.0%. It is possible that the aldehyde at higher concentrations has the same effects on the lysosomal membrane as freeze-thawing. Glucose-6-phosphatase activity was well-preserved in a microsomal fraction fixed with 0.01% glutaraldehyde but was decreased drastically when the concentration of the aldehyde was greater than 0.05%."} {"id": "PMID:178636", "title": "Collaborative study of an improved method for the enumeration and confirmation of Clostridium perfringens in foods.", "content": "A collaborative study was conducted in 10 laboratories to evaluate the performance of a new method for the enumeration of vegetative cells of Clostridium perfringens in foods. Results obtained by the new method were compared with results from the official first action method, 46.049-46.053. Per cent recoveries of 4 C. perfringens strains from inoculated roast beef samples were higher and more consistent in tryptose-sulfite-cycloserine (TSC) agar with or without added egg yolk than in sulfite-polymyxin-sulfadiazine (SPS) agar, specified in the official first action method. The confirmatory technique utilized in the new method was also found to be more reliable than the technique described in the official first action method. Based on the collaborative results, the new method with TSC agar for enumeration and a modified motility-nitrate medium together with a lactose-gelatin medium for confirmation of C. perfringens has been adopted as official first action to replace 46.049-46.053.", "contents": "Collaborative study of an improved method for the enumeration and confirmation of Clostridium perfringens in foods. A collaborative study was conducted in 10 laboratories to evaluate the performance of a new method for the enumeration of vegetative cells of Clostridium perfringens in foods. Results obtained by the new method were compared with results from the official first action method, 46.049-46.053. Per cent recoveries of 4 C. perfringens strains from inoculated roast beef samples were higher and more consistent in tryptose-sulfite-cycloserine (TSC) agar with or without added egg yolk than in sulfite-polymyxin-sulfadiazine (SPS) agar, specified in the official first action method. The confirmatory technique utilized in the new method was also found to be more reliable than the technique described in the official first action method. Based on the collaborative results, the new method with TSC agar for enumeration and a modified motility-nitrate medium together with a lactose-gelatin medium for confirmation of C. perfringens has been adopted as official first action to replace 46.049-46.053."} {"id": "PMID:178638", "title": "Studies on pig serum lipoproteins. I. Separation and properties of low-density lipoproteins.", "content": "The low-density lipoproteins in pig serum were separated into two subclasses (LDL1 and LDL2) by 2 to 7% pore size gradient gel electrophoresis. Preparative gel electrophoresis in 2 to 4% gradient gel made it possible to isolate these components as distinct entities. After delipidation by chromatography on Sepharose 4B in the presence of SDS, both apo-LDL1 and apo-LDL2 were found to have a molecular weight of 2.6X10(5). However, when these apoproteins were incubated in 10% sodium dodecyl sulfate, fragmentation occurred and the minimum fragment molecular weight was estimated to be 2.4X10(4). No essential difference was found in the amino acid compositions or fragmentation patterns of the apoproteins. However, the amounts of carbohydrates in the two apoproteins were different (7.09% in apo-LDL1 and 5.08% in apo-LDL2). The carbohydrate composition was 0.8% sialic acid, 2.38% N-acetyl-glucosamine, and 4.01% neutral sugars in apo-LDL1 and 0.5, 1.75, and 2.83% in apo-LDL2, respectively. In both apoproteins, mannose, galactose, and fucose were present in almost the same molar ratio of 4-5 : 2-3 : 1.", "contents": "Studies on pig serum lipoproteins. I. Separation and properties of low-density lipoproteins. The low-density lipoproteins in pig serum were separated into two subclasses (LDL1 and LDL2) by 2 to 7% pore size gradient gel electrophoresis. Preparative gel electrophoresis in 2 to 4% gradient gel made it possible to isolate these components as distinct entities. After delipidation by chromatography on Sepharose 4B in the presence of SDS, both apo-LDL1 and apo-LDL2 were found to have a molecular weight of 2.6X10(5). However, when these apoproteins were incubated in 10% sodium dodecyl sulfate, fragmentation occurred and the minimum fragment molecular weight was estimated to be 2.4X10(4). No essential difference was found in the amino acid compositions or fragmentation patterns of the apoproteins. However, the amounts of carbohydrates in the two apoproteins were different (7.09% in apo-LDL1 and 5.08% in apo-LDL2). The carbohydrate composition was 0.8% sialic acid, 2.38% N-acetyl-glucosamine, and 4.01% neutral sugars in apo-LDL1 and 0.5, 1.75, and 2.83% in apo-LDL2, respectively. In both apoproteins, mannose, galactose, and fucose were present in almost the same molar ratio of 4-5 : 2-3 : 1."} {"id": "PMID:178639", "title": "Glycolipids of the fish testis.", "content": "Glycolipids were purified from the total lipid extract of the testis or milt of a kind of puffer (Fugu rubripes rubripes) by adsorption column chromatography using silicic acid and magnesium silicate and by preparative silica gel TLC. The glycolipids were identified as glucosylceramide (116 mug/g wet tissue) and galactosylceramide 26.7 mug/g). Seminolipid, a sulfagalactolipid specific to mammalian testis was not detected, but the presence of a small amount of sulfatide (15.2 mug/g) was demonstrated. The long-chain bases of both cerebrosides were mainly C18-sphingenine, but in sulfatide, C20-sphingenine was more abundant than C18-sphingenine. In both cerebrosides and sulfatide, the fatty acid compositions were similar, with nervonic acid as the predominant component. Two species of gangliosides were also obtained and were identified as N-acetylgalactosaminyl(1 leads to 4)[N-acetylneuraminyl(2 leads to 3)]galactosyl(1leads to 4)glucosylceramide (59.8 mug/g) and N-acetylneuraminyl(2 leads to 3)galactosyl(1 leads to 4)N-acetylglucosaminyl(1 leads to 3)galactosyl(1 leads to 4)glucosylceramide (45.0 mug/g). The long-chain bases of the two gangliosides consisted of C18-spingenine and C20-sphingenine, and the major fatty acids were palmitic and stearic acids.", "contents": "Glycolipids of the fish testis. Glycolipids were purified from the total lipid extract of the testis or milt of a kind of puffer (Fugu rubripes rubripes) by adsorption column chromatography using silicic acid and magnesium silicate and by preparative silica gel TLC. The glycolipids were identified as glucosylceramide (116 mug/g wet tissue) and galactosylceramide 26.7 mug/g). Seminolipid, a sulfagalactolipid specific to mammalian testis was not detected, but the presence of a small amount of sulfatide (15.2 mug/g) was demonstrated. The long-chain bases of both cerebrosides were mainly C18-sphingenine, but in sulfatide, C20-sphingenine was more abundant than C18-sphingenine. In both cerebrosides and sulfatide, the fatty acid compositions were similar, with nervonic acid as the predominant component. Two species of gangliosides were also obtained and were identified as N-acetylgalactosaminyl(1 leads to 4)[N-acetylneuraminyl(2 leads to 3)]galactosyl(1leads to 4)glucosylceramide (59.8 mug/g) and N-acetylneuraminyl(2 leads to 3)galactosyl(1 leads to 4)N-acetylglucosaminyl(1 leads to 3)galactosyl(1 leads to 4)glucosylceramide (45.0 mug/g). The long-chain bases of the two gangliosides consisted of C18-spingenine and C20-sphingenine, and the major fatty acids were palmitic and stearic acids."} {"id": "PMID:178640", "title": "A new assay method for hydrogenase based on an enzymic electrode reaction. The enzymic electric cell method.", "content": "A new assay method for hydrogenase [EC 1.12.2.1] based on the enzymic electrode reaction of H2-H+ equilibrium has been established. The method is based on the experimental fact that the short-circuit current of the electric cell composed of an electrode with hydrogenase and methylviologen as the mediator of H2-H+ equilibrium and a saturated calomel electrode as the counter electrode, is practically proportional to the amount of hydrogenase in the cell. The new method is referred to as the \"enzymic electric cell method.\" This technique has applications not only to routine activity assay but also to the direct determination of the time course of enzyme denaturation, which has not previously been possible.", "contents": "A new assay method for hydrogenase based on an enzymic electrode reaction. The enzymic electric cell method. A new assay method for hydrogenase [EC 1.12.2.1] based on the enzymic electrode reaction of H2-H+ equilibrium has been established. The method is based on the experimental fact that the short-circuit current of the electric cell composed of an electrode with hydrogenase and methylviologen as the mediator of H2-H+ equilibrium and a saturated calomel electrode as the counter electrode, is practically proportional to the amount of hydrogenase in the cell. The new method is referred to as the \"enzymic electric cell method.\" This technique has applications not only to routine activity assay but also to the direct determination of the time course of enzyme denaturation, which has not previously been possible."} {"id": "PMID:178641", "title": "Isolation and characterization of serologically active phosphatidylinositol oligomannosides of Mycobacterium tuberculosis.", "content": "Phospholipids extracted with hot methanol from Mycobacterium tuberculosis, strain H37Rv, were fractionated with solvent mixtures and by partition chromatography on silica-gel columns. Of 12 components detected on a thin-layer chromatogram of the total phospholipid fraction, 6 components were purified. They were all phosphatidylinositol oligomannosides: two hexamannosides (H-2 and H-3), one tetramannoside (H-4), one trimannoside (H-5), and two dimannosides (H-6 and H-7). The molar ratios of fatty acid to phosphorus were 3 for H-2, H-4, H-5, and H-6, and 4 for H-3 and H-7. In each lipid, more than 80% of the total fatty acids were palmitic and tuberculostearic acids. Each of the six lipids had serological activity to various degrees.", "contents": "Isolation and characterization of serologically active phosphatidylinositol oligomannosides of Mycobacterium tuberculosis. Phospholipids extracted with hot methanol from Mycobacterium tuberculosis, strain H37Rv, were fractionated with solvent mixtures and by partition chromatography on silica-gel columns. Of 12 components detected on a thin-layer chromatogram of the total phospholipid fraction, 6 components were purified. They were all phosphatidylinositol oligomannosides: two hexamannosides (H-2 and H-3), one tetramannoside (H-4), one trimannoside (H-5), and two dimannosides (H-6 and H-7). The molar ratios of fatty acid to phosphorus were 3 for H-2, H-4, H-5, and H-6, and 4 for H-3 and H-7. In each lipid, more than 80% of the total fatty acids were palmitic and tuberculostearic acids. Each of the six lipids had serological activity to various degrees."} {"id": "PMID:178642", "title": "M\u00f6ssbauer effect and electron paramagnetic resonance studies on yeast aconitase.", "content": "M\u00f6ssbauer effect and electron paramagnetic resonance (EPR) were measured for yeast aconitase [EC 4.2.1.3] purified from the cells of Candida lipolytica (ATCC 200114). M\u00f6ssbauer spectra suggested that yeast aconitase nostly contained two high-spin Fe(III) ions in an antiferromagnetically coupled binuclear complex that resembled oxidized 2 Fe ferredoxins, together with a small amount of high-spin Fe(II). EPR spectra recorded no signal at 77degreesK, but showed a slightly asymmetric signal centered at g=2.0 at 4.2degreesK, presumably due to the small amount of Fe(II) Fe(III) pairs.", "contents": "M\u00f6ssbauer effect and electron paramagnetic resonance studies on yeast aconitase. M\u00f6ssbauer effect and electron paramagnetic resonance (EPR) were measured for yeast aconitase [EC 4.2.1.3] purified from the cells of Candida lipolytica (ATCC 200114). M\u00f6ssbauer spectra suggested that yeast aconitase nostly contained two high-spin Fe(III) ions in an antiferromagnetically coupled binuclear complex that resembled oxidized 2 Fe ferredoxins, together with a small amount of high-spin Fe(II). EPR spectra recorded no signal at 77degreesK, but showed a slightly asymmetric signal centered at g=2.0 at 4.2degreesK, presumably due to the small amount of Fe(II) Fe(III) pairs."} {"id": "PMID:178643", "title": "Effects of ethyl p-chlorophenoxyisobutyrate on carbohydrate and fatty acid metabolism in rat liver.", "content": "1. Rats were fed on a diet containing ethyl p-chlorophenoxyisobutyrate (0.3%, w/w) for 14 days. 2. The alterations of contents of intermediates in the liver indicate that gluconeogenesis is inhibited at the reaction(s) between 3-phosphoglycerate and fructose 1,6-diphosphate. The [nad+]/([nadh] ratios in cytoplasm and mitochondria were increased about 3- and 4-fold, respectively. Marked increases in the contents of CoA and its thioesters were found. 3. Hepatic fatty acid synthesis increased about 3-fold. There was no evidence of inhibition of the acetyl-CoA carboxylase [EC 6.4.1.2] reaction by the drug.", "contents": "Effects of ethyl p-chlorophenoxyisobutyrate on carbohydrate and fatty acid metabolism in rat liver. 1. Rats were fed on a diet containing ethyl p-chlorophenoxyisobutyrate (0.3%, w/w) for 14 days. 2. The alterations of contents of intermediates in the liver indicate that gluconeogenesis is inhibited at the reaction(s) between 3-phosphoglycerate and fructose 1,6-diphosphate. The [nad+]/([nadh] ratios in cytoplasm and mitochondria were increased about 3- and 4-fold, respectively. Marked increases in the contents of CoA and its thioesters were found. 3. Hepatic fatty acid synthesis increased about 3-fold. There was no evidence of inhibition of the acetyl-CoA carboxylase [EC 6.4.1.2] reaction by the drug."} {"id": "PMID:178644", "title": "Comparative specificity of geranylgeranyl pyrophosphate synthetase of Micrococcus lysodeikticus and pumpkin.", "content": "Comparative studies on the substrate specificity of geranylgeranyl pyrophosphate synthetase from Micrococcus lysodeikticus and from pumpkin seedlin revealed that geranyl pyrophosphate was the most active of the natural substrates for the pumpkin enzyme, whereas it was the least active for the bacterial enzyme. A marked difference was also observed between the enzymes from these two sources as regards the reactivity of 3-methyl-2-alkenyl pyrophosphates as a function of the size of the alkyl group.", "contents": "Comparative specificity of geranylgeranyl pyrophosphate synthetase of Micrococcus lysodeikticus and pumpkin. Comparative studies on the substrate specificity of geranylgeranyl pyrophosphate synthetase from Micrococcus lysodeikticus and from pumpkin seedlin revealed that geranyl pyrophosphate was the most active of the natural substrates for the pumpkin enzyme, whereas it was the least active for the bacterial enzyme. A marked difference was also observed between the enzymes from these two sources as regards the reactivity of 3-methyl-2-alkenyl pyrophosphates as a function of the size of the alkyl group."} {"id": "PMID:178645", "title": "Nucleoside diphosphate kinase and the flagellar movement of glycerinated spermatozoa.", "content": "Nucleoside diphosphate kinase [EC 2.7.4.6.] of sperm flagella and Tetrahymena cilia is detected mostly in the outer fiber fraction, suggesting an association of the enzyme with the outer fiber microtubules. The enzyme does not catalyze transphosphorylation between microtubule-bound GDP and exogenous ATP. Even when undulatory movement of glycerinated sperm is induced by MgATP, no phosphorylation is detected in the outer fiber fraction. These facts do not appear to support the hypothesis that the phosphorylation of microtubule-bound GDP is involved in the mechanism of flagellar movement.", "contents": "Nucleoside diphosphate kinase and the flagellar movement of glycerinated spermatozoa. Nucleoside diphosphate kinase [EC 2.7.4.6.] of sperm flagella and Tetrahymena cilia is detected mostly in the outer fiber fraction, suggesting an association of the enzyme with the outer fiber microtubules. The enzyme does not catalyze transphosphorylation between microtubule-bound GDP and exogenous ATP. Even when undulatory movement of glycerinated sperm is induced by MgATP, no phosphorylation is detected in the outer fiber fraction. These facts do not appear to support the hypothesis that the phosphorylation of microtubule-bound GDP is involved in the mechanism of flagellar movement."} {"id": "PMID:178646", "title": "Change in the ratio of cytochrome oxidase activity to nitrite reductase activity of Pseudomonas aeruginosa nitrite reductase with the kind of C-type cytochrome used as an electron donor.", "content": "The ratio between the nitrite reductase and cytochrome oxidase activities of Pseudomonas aeruginosa nitrite reductase [EC 1.9.3.2.] varies with kind of C-type cytochrome used as the electron donor. Withe cytochrome c-548, 554 (Micrococcus sp.), the nitrite reductase activity is greater than the cytochrome oxidase activity, while the former is smaller than the latter with cytochrome c-554 (Navicula pelliculosa). The aerobic oxidation catalyzed by this enzyme of denitrifying bacterial ferrocytochrome c is greatly accelerated on addition of nitrite, while that of the algal ferrocytochrome c is not affected or is even depressed by the salt. An accelerative effect of nitrite is generally observed with many kinds of C-type cytochromes which react with the enzyme very or fairly rapidly. The difference in the ratio of the two activities of the enzyme seems to arise according to whether or not nitrite affects the interaction of C-type cytochrome with the enzyme.", "contents": "Change in the ratio of cytochrome oxidase activity to nitrite reductase activity of Pseudomonas aeruginosa nitrite reductase with the kind of C-type cytochrome used as an electron donor. The ratio between the nitrite reductase and cytochrome oxidase activities of Pseudomonas aeruginosa nitrite reductase [EC 1.9.3.2.] varies with kind of C-type cytochrome used as the electron donor. Withe cytochrome c-548, 554 (Micrococcus sp.), the nitrite reductase activity is greater than the cytochrome oxidase activity, while the former is smaller than the latter with cytochrome c-554 (Navicula pelliculosa). The aerobic oxidation catalyzed by this enzyme of denitrifying bacterial ferrocytochrome c is greatly accelerated on addition of nitrite, while that of the algal ferrocytochrome c is not affected or is even depressed by the salt. An accelerative effect of nitrite is generally observed with many kinds of C-type cytochromes which react with the enzyme very or fairly rapidly. The difference in the ratio of the two activities of the enzyme seems to arise according to whether or not nitrite affects the interaction of C-type cytochrome with the enzyme."} {"id": "PMID:178647", "title": "Surface alterations in calf lymphocytes oxidized by sodium periodate.", "content": "In order to investigate alterations in surface structure in transformed lymphocytes, calf submandibular lymph node cell suspensions were oxidized with NaIO4. Oxidezed lymphocytes were morphologically transformed and had higher rates of DNA synthesis by 2 days after treatment. These results were prevented by reduction of the cell suspension with NaBH4, or by neuraminidase treatment of cells prior to oxidation. The amount of 125I-labeled Agaricus bisporus lectin bound to cells immediately after oxidation and the affinity constant for binding were increased over 2-fold, while cells immediately following oxidation and reduction showed decreased receptors with still higher affinity for the lectin compared to untreated cells. The amount of Phaseolus vulgaris lectin bound to oxidezed cells was also increased, but affinity was unchanged. Immediately following oxidation and reduction, these receptor sites were unchanged in number and affinity from untreated cells. In contrast, the number and affinity of receptors for concanavalin A were not changed immediately after oxidation or oxidation and reduction. In order to define the extent of compositional changes in surface glycoprotein receptors, plasma membranes were isolated from frozen calf submandibular lymph nodes. Compared to untreated plasma membranes, oxidezed membranes had similar contents of galactose, mannose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and amino acids. Sialic acid content of oxidized membranes was reduced when measured by thiobarbituric acid assay. Sialic acids of untreated plasma membranes co-chromatographed with N-glycolylneurominic acid and N-acetylneuraminic acid, while those of oxidized membranes co-chromatographed with N-glycolylneuraminic acid and 5-acetamido-3,5-dideoxy-L-arabino-7-aldehydo-2-heptulosonic acid. Therefore, specific surface conformational changes in certain classes of membrane glycoproteins are associated with mild Malapradian oxidation of membrane sialic acids. These temporally precede NaIO4-induced transformation of calf lymphocytes. This is consistent with an hypothesis of membrane-mediated stimulation of lymphocyte transformation.", "contents": "Surface alterations in calf lymphocytes oxidized by sodium periodate. In order to investigate alterations in surface structure in transformed lymphocytes, calf submandibular lymph node cell suspensions were oxidized with NaIO4. Oxidezed lymphocytes were morphologically transformed and had higher rates of DNA synthesis by 2 days after treatment. These results were prevented by reduction of the cell suspension with NaBH4, or by neuraminidase treatment of cells prior to oxidation. The amount of 125I-labeled Agaricus bisporus lectin bound to cells immediately after oxidation and the affinity constant for binding were increased over 2-fold, while cells immediately following oxidation and reduction showed decreased receptors with still higher affinity for the lectin compared to untreated cells. The amount of Phaseolus vulgaris lectin bound to oxidezed cells was also increased, but affinity was unchanged. Immediately following oxidation and reduction, these receptor sites were unchanged in number and affinity from untreated cells. In contrast, the number and affinity of receptors for concanavalin A were not changed immediately after oxidation or oxidation and reduction. In order to define the extent of compositional changes in surface glycoprotein receptors, plasma membranes were isolated from frozen calf submandibular lymph nodes. Compared to untreated plasma membranes, oxidezed membranes had similar contents of galactose, mannose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and amino acids. Sialic acid content of oxidized membranes was reduced when measured by thiobarbituric acid assay. Sialic acids of untreated plasma membranes co-chromatographed with N-glycolylneurominic acid and N-acetylneuraminic acid, while those of oxidized membranes co-chromatographed with N-glycolylneuraminic acid and 5-acetamido-3,5-dideoxy-L-arabino-7-aldehydo-2-heptulosonic acid. Therefore, specific surface conformational changes in certain classes of membrane glycoproteins are associated with mild Malapradian oxidation of membrane sialic acids. These temporally precede NaIO4-induced transformation of calf lymphocytes. This is consistent with an hypothesis of membrane-mediated stimulation of lymphocyte transformation."} {"id": "PMID:178648", "title": "Preparation and characterization of eukaryotic initiation factor EIF-3. Formation of binary (EIF-3-Met-tRNAf) and ternary (EIF-3-Met-tRNAf-GTP) complexes.", "content": "The 133,000 X g supernatant fraction prepared from ascites cells in 20 mM KCl (low CKl supernatant) contained the initiation factors EIF-1 and EIF-2 (and the elongation factore EF-1 and EF-2) but lacked EIF-3; thus, low KCl supernatant could be used to assay for EIF-3. EIF-3 was prepared from a crude initiation factor perparation (a 250 mM KCl extract of ascites cell ribosomes precipitated with 70% saturated ammonium sulfate) by chromatography on DEAE-Sephadex A-50 and hydroxylapatite. The EIF-O had no detectable EIF-1 and little or no EIF-2. Factor EIF-3 was required fro translation of encephalomyocarditis virus RNA. The molecular weight of EIF-3 was estimated by Sephadex G-200 filtration to be 139,000; the sedimentation coefficient was calculated to be about 5.8. EIF-3 formed a binary complex specifically with the initiator tRNA, Met-tRNAf, and if GTP was present the factor formed a ternary complex (EIF-3-Met-tRNAf-GTP). The EIF-3 preparation had no methionyl-tRNA synthetase activity to account for binding. Complex-formation was with eukaryotic Met-tRNAf and no other aminoacyl-tRNA. The binary and ternary complexes were retained quantitatively on Millipore filters (which was the most convenient assay), but they could also be demonstrated by filtration through Sephadex G-100 or by glycerol gradient centrifugation. GTP increased the rate, the amount, and the stability of complex formed; the ration of GTP to Met-tRNAf in the ternary complex appeared to be 1. The binary and the ternary complexes transferred Met-tRNAf to the 40 S ribosomal subunits, but not to 60 S subparticles. The factor-dependent binding of Met-tRNAf to the 40 S subunit did not require mRNA (or GTP). In the presence of 60 S subunits, the initiator tRNA bound to 40 S subunits was not transferred to 80 S ribosomes even if mRNA was added--that reaction may require another initiation factor. Treatment of EIF-3 with N-ethylmaleimide led to loss of its activity in complex formation and in support of the translation of encephalomyocarditis virus RNA. In addition to forming the binary and ternary complexes, and supporting the translation of encephalomyocarditis virus RNA, EIF-3 also increases the number of free ribosomal subunits by either preventing their association or causing dissociation of 80 S couples.", "contents": "Preparation and characterization of eukaryotic initiation factor EIF-3. Formation of binary (EIF-3-Met-tRNAf) and ternary (EIF-3-Met-tRNAf-GTP) complexes. The 133,000 X g supernatant fraction prepared from ascites cells in 20 mM KCl (low CKl supernatant) contained the initiation factors EIF-1 and EIF-2 (and the elongation factore EF-1 and EF-2) but lacked EIF-3; thus, low KCl supernatant could be used to assay for EIF-3. EIF-3 was prepared from a crude initiation factor perparation (a 250 mM KCl extract of ascites cell ribosomes precipitated with 70% saturated ammonium sulfate) by chromatography on DEAE-Sephadex A-50 and hydroxylapatite. The EIF-O had no detectable EIF-1 and little or no EIF-2. Factor EIF-3 was required fro translation of encephalomyocarditis virus RNA. The molecular weight of EIF-3 was estimated by Sephadex G-200 filtration to be 139,000; the sedimentation coefficient was calculated to be about 5.8. EIF-3 formed a binary complex specifically with the initiator tRNA, Met-tRNAf, and if GTP was present the factor formed a ternary complex (EIF-3-Met-tRNAf-GTP). The EIF-3 preparation had no methionyl-tRNA synthetase activity to account for binding. Complex-formation was with eukaryotic Met-tRNAf and no other aminoacyl-tRNA. The binary and ternary complexes were retained quantitatively on Millipore filters (which was the most convenient assay), but they could also be demonstrated by filtration through Sephadex G-100 or by glycerol gradient centrifugation. GTP increased the rate, the amount, and the stability of complex formed; the ration of GTP to Met-tRNAf in the ternary complex appeared to be 1. The binary and the ternary complexes transferred Met-tRNAf to the 40 S ribosomal subunits, but not to 60 S subparticles. The factor-dependent binding of Met-tRNAf to the 40 S subunit did not require mRNA (or GTP). In the presence of 60 S subunits, the initiator tRNA bound to 40 S subunits was not transferred to 80 S ribosomes even if mRNA was added--that reaction may require another initiation factor. Treatment of EIF-3 with N-ethylmaleimide led to loss of its activity in complex formation and in support of the translation of encephalomyocarditis virus RNA. In addition to forming the binary and ternary complexes, and supporting the translation of encephalomyocarditis virus RNA, EIF-3 also increases the number of free ribosomal subunits by either preventing their association or causing dissociation of 80 S couples."} {"id": "PMID:178649", "title": "Complete amino acid analysis of proteins from a single hydrolysate.", "content": "An analytical procedure which affords the precise amino acid composition of a protein or a peptide from a single hydrolysate is described. This method utilizes 4 N methanesulfonic acid containing 0.2% 3-(2-aminoethyl)indole, rather then 6N HCl as a catalyst for hydrolysis. The hydrolysis is carried out in vacuo (20 mu) at 115 degrees for 22 to 72 hours. Half-cystine is determined as S-sulfocysteine by treating the hydrolysate with dithiothreitol followed by an excess of tetrathionate. The values of all amino acids, including tryptophan and half-cystine, were close to the expected theoretical values for the proteins examined. The method has the advantage that the neutralized hydrolysate can be applied directly to an ion exchange column. Further, the method is capable of distinguishing between free sulfhydryl groups as S-carbosymethylcysteine and disulfides as S-sulfocysteine. A limitation of the procedure is that tryptophan remains sensitive to the presence of carbohydrate in the sample.", "contents": "Complete amino acid analysis of proteins from a single hydrolysate. An analytical procedure which affords the precise amino acid composition of a protein or a peptide from a single hydrolysate is described. This method utilizes 4 N methanesulfonic acid containing 0.2% 3-(2-aminoethyl)indole, rather then 6N HCl as a catalyst for hydrolysis. The hydrolysis is carried out in vacuo (20 mu) at 115 degrees for 22 to 72 hours. Half-cystine is determined as S-sulfocysteine by treating the hydrolysate with dithiothreitol followed by an excess of tetrathionate. The values of all amino acids, including tryptophan and half-cystine, were close to the expected theoretical values for the proteins examined. The method has the advantage that the neutralized hydrolysate can be applied directly to an ion exchange column. Further, the method is capable of distinguishing between free sulfhydryl groups as S-carbosymethylcysteine and disulfides as S-sulfocysteine. A limitation of the procedure is that tryptophan remains sensitive to the presence of carbohydrate in the sample."} {"id": "PMID:178650", "title": "Investigations of equilibrium complexes of myoxin subfragment 1 with the manganous ion and adenosine diphosphate using magnetic resonance techniques.", "content": "Electron paramagnetic resonance spectroscopy and water proton relaxation rate (PRR) measurements were used to characterize a complex formed at the myosin subfragment 1 (S1) ATPase site with stoichiometric amounts of Mn(II) and ADP. In the absence of nucleotide, Mn(II) binding at the active site is very weak, although two other classes of sites for Mn(II) on subfragment 1 were identified which are not directly involved in the ATPase reaction. A high affinity Mn(II) site (termed L-site with KL = 3 muM) is associated with a region of the molecule which is susceptible to proteolysis (probably the LC2 light chain subunit) since its stoichiometry depends on the conditions employed for the preparation of subfragment 1 during the papain treatment of myosin. In addition there are a number of weak sites for Mn(II) (termed N-sites) probably associated with anionic groups on the surface of the molecule. In order to study the properties of Mn(II) and ADP bound at the active site by magnetic resonance techniques, subfragment 1 preparations virtually free of the L-site were used, since such an ancillary site competes for the available Mn(II). MnADP binds to subfragment 1 with an apparent dissociation constant, KT, of about 4 muM at 25 degrees. The resultant complex, S1-MnADP, has a low PRR enhancement factor (1.7 at 24.3 MHZ), and its frequency (magnetic field) dependence indicates that this is because there are no readily exchangeable water molecules within the first coordination sphere of Mn(II. Relaxation of the bulk solvent is mediated by protons bound transiently within the outer spheres (4 to 7 A) of the Mn(II). A nitroxide spin label attached to the reactive thiol group of subfragment 1 enhances the solvent PRR, and this property is sensitive to the binding of MgADP to the active site. However, no dipolar spin-spin interaction was detected between the nitroxide group and Mn(II) in the S1-MnADP complex, indicating that the metal ion and thiol group are well separated.", "contents": "Investigations of equilibrium complexes of myoxin subfragment 1 with the manganous ion and adenosine diphosphate using magnetic resonance techniques. Electron paramagnetic resonance spectroscopy and water proton relaxation rate (PRR) measurements were used to characterize a complex formed at the myosin subfragment 1 (S1) ATPase site with stoichiometric amounts of Mn(II) and ADP. In the absence of nucleotide, Mn(II) binding at the active site is very weak, although two other classes of sites for Mn(II) on subfragment 1 were identified which are not directly involved in the ATPase reaction. A high affinity Mn(II) site (termed L-site with KL = 3 muM) is associated with a region of the molecule which is susceptible to proteolysis (probably the LC2 light chain subunit) since its stoichiometry depends on the conditions employed for the preparation of subfragment 1 during the papain treatment of myosin. In addition there are a number of weak sites for Mn(II) (termed N-sites) probably associated with anionic groups on the surface of the molecule. In order to study the properties of Mn(II) and ADP bound at the active site by magnetic resonance techniques, subfragment 1 preparations virtually free of the L-site were used, since such an ancillary site competes for the available Mn(II). MnADP binds to subfragment 1 with an apparent dissociation constant, KT, of about 4 muM at 25 degrees. The resultant complex, S1-MnADP, has a low PRR enhancement factor (1.7 at 24.3 MHZ), and its frequency (magnetic field) dependence indicates that this is because there are no readily exchangeable water molecules within the first coordination sphere of Mn(II. Relaxation of the bulk solvent is mediated by protons bound transiently within the outer spheres (4 to 7 A) of the Mn(II). A nitroxide spin label attached to the reactive thiol group of subfragment 1 enhances the solvent PRR, and this property is sensitive to the binding of MgADP to the active site. However, no dipolar spin-spin interaction was detected between the nitroxide group and Mn(II) in the S1-MnADP complex, indicating that the metal ion and thiol group are well separated."} {"id": "PMID:178651", "title": "Cytochrome c1 of bakers' yeast. I. Isolation and properties.", "content": "Cytochrome c1 has been purified from mitochondria of the yeast Saccharomyces cerevisiae. The procedure involves solubilization withcholate, ammonium sulfate fractionation, disruption of the dytochrome b-c1 complex with mercaptoethanol and detergents, and chromatography on DEAE-cellulose. The final product is psectrally pure, contains up to 62 nmol of covalently bound heme per mg of protein and does not react with oxygen or carbon monoxide. Sodium dodecyl sulfate disaggregates the purified cytochrome into a single 31,000 dalton subunit carrying the covalently attached heme group. Many cytochrome c1 preparations contain in addition an 18,500 dalton polypeptide which is devoid of covalently bound heme. Since this polypeptide can be removed from the heme-carrying polypeptide by relatively mild procedures, it is probably not an essential subunit of cytochrome c1. Cytochrome c1 is extremely sensitive to proteolysis. If it si purified in the absence of protease inhibitors, a family of heme polypeptides with molecular weights of 29,000, 27,000, and 25,000 daltons is obtained. In the presence of the protease inhibitor phenylmethylsulfonylfluoride the purification yields predominantly a 31,000 dalton heme protein with only little contamination by a 29,000 dalton degradation product. In order to show that only the 31,000 dalton heme-polypeptide is the native species, yeast cells were labeled with the heme-precursor delta-amino[3H]levulinic acid, converted to protoplasts and directly lysed with dodecyl sulfate in the presence of protease inhibitors. Subsequent electrophoresis of the lysate in the presence of dodecyl sulfate reveals the covalently bound heme of cytochrome c1 as a single symmetrical peak at 31,000 daltons.", "contents": "Cytochrome c1 of bakers' yeast. I. Isolation and properties. Cytochrome c1 has been purified from mitochondria of the yeast Saccharomyces cerevisiae. The procedure involves solubilization withcholate, ammonium sulfate fractionation, disruption of the dytochrome b-c1 complex with mercaptoethanol and detergents, and chromatography on DEAE-cellulose. The final product is psectrally pure, contains up to 62 nmol of covalently bound heme per mg of protein and does not react with oxygen or carbon monoxide. Sodium dodecyl sulfate disaggregates the purified cytochrome into a single 31,000 dalton subunit carrying the covalently attached heme group. Many cytochrome c1 preparations contain in addition an 18,500 dalton polypeptide which is devoid of covalently bound heme. Since this polypeptide can be removed from the heme-carrying polypeptide by relatively mild procedures, it is probably not an essential subunit of cytochrome c1. Cytochrome c1 is extremely sensitive to proteolysis. If it si purified in the absence of protease inhibitors, a family of heme polypeptides with molecular weights of 29,000, 27,000, and 25,000 daltons is obtained. In the presence of the protease inhibitor phenylmethylsulfonylfluoride the purification yields predominantly a 31,000 dalton heme protein with only little contamination by a 29,000 dalton degradation product. In order to show that only the 31,000 dalton heme-polypeptide is the native species, yeast cells were labeled with the heme-precursor delta-amino[3H]levulinic acid, converted to protoplasts and directly lysed with dodecyl sulfate in the presence of protease inhibitors. Subsequent electrophoresis of the lysate in the presence of dodecyl sulfate reveals the covalently bound heme of cytochrome c1 as a single symmetrical peak at 31,000 daltons."} {"id": "PMID:178652", "title": "Cytochrome c1 of bakers' yeast. II. Synthesis on cytoplasmic robosomes and influence of oxygen and heme on accumulation of the apoprotein.", "content": "In the preceding paper (Ross, E., and Schatz, G. (1976) J. Biol. Chem. 251, 1991-1996) yeast cytochrome c1 was characterized as a 31,000 dalton polypeptide with a covalently bound heme group. In order to determine the site of translation of this heme-carrying polypeptide, yeast cells were labeled with [H]leu(be under the following conditions: (a) in the absence of inhibitors, (b) in the presence of acriflavin (an inhibitor of mitochondrial translation), or (c) in the presence of cycloheximide (an inhibitor of cytoplasmic translation). The incorporation of radioactivity into the hemeprotein was measured by immunoprecipitating it from mitochondrial extracts and analyzing it by dodecyl sulfate-polyacrylamide gel electrophoresis. Label was incorporated into the cytochrome c1 apoprotein only in the presence of acriflavin or in the absence of inhibitor, but not in the presence of cycloheximide. Cytochrome c1 is thus a cytoplasmic translation product. This conclusion was further supported by the demonstration that a cytolasmic petite mutant lacking mitochondrial protein synthesis still contained holocytochrome c1 that was indistinguishable from cytochrome c1 of wild type yeast with respect to molecular weight, absorption spectru, the presence of a covalently bound heme group, and antigenic properties. Cytochrome c1 in the mitochondria of the cytoplasmic petite mutant is firmly bound to the membrane, and its concentration approaches that typical of wild type mitochondria. However, its lability to proteolysis appeared to be increased. A mitochondrial translation product may thus be necessary for the correct conformation or orientation of cytochrome c1 in the mitochondrial inner membrane. Accumulation of cytochrome c1 protein in mitochondria is dependent on the abailability of heme. This was shown with a delta-aminolevulinic acid synthetase-deficient yeast mutant which lacks heme and any light-absorbing peaks attributable to cytochromes. Mitochondria from mutant cells grown without added delta-aminolevulinic acid contained at least 20 times less protein immunoprecipitable by cytochrome c1-antisera than mitochondria from cells grown in the presence of the heme precursor. Similarly, the respiration-deficient promitochondria of anaerobically grown wild type cells are almost completely devoid of material cross-reacting with cytochrome c1-antisera. A 105,000 X g supernatant of aerobically grown wild type cells contains a 29,000 dalton polypeptide that is precipitated by cytochrome c1-antiserum but not by nonimmune serum. This polypeptide is also present in high speed supernatants from the heme-deficient mutant or from anaerobically gorwn wild type cells. The possible identity of this polypeptide with soluble apocytochrome c1 is being investigated.", "contents": "Cytochrome c1 of bakers' yeast. II. Synthesis on cytoplasmic robosomes and influence of oxygen and heme on accumulation of the apoprotein. In the preceding paper (Ross, E., and Schatz, G. (1976) J. Biol. Chem. 251, 1991-1996) yeast cytochrome c1 was characterized as a 31,000 dalton polypeptide with a covalently bound heme group. In order to determine the site of translation of this heme-carrying polypeptide, yeast cells were labeled with [H]leu(be under the following conditions: (a) in the absence of inhibitors, (b) in the presence of acriflavin (an inhibitor of mitochondrial translation), or (c) in the presence of cycloheximide (an inhibitor of cytoplasmic translation). The incorporation of radioactivity into the hemeprotein was measured by immunoprecipitating it from mitochondrial extracts and analyzing it by dodecyl sulfate-polyacrylamide gel electrophoresis. Label was incorporated into the cytochrome c1 apoprotein only in the presence of acriflavin or in the absence of inhibitor, but not in the presence of cycloheximide. Cytochrome c1 is thus a cytoplasmic translation product. This conclusion was further supported by the demonstration that a cytolasmic petite mutant lacking mitochondrial protein synthesis still contained holocytochrome c1 that was indistinguishable from cytochrome c1 of wild type yeast with respect to molecular weight, absorption spectru, the presence of a covalently bound heme group, and antigenic properties. Cytochrome c1 in the mitochondria of the cytoplasmic petite mutant is firmly bound to the membrane, and its concentration approaches that typical of wild type mitochondria. However, its lability to proteolysis appeared to be increased. A mitochondrial translation product may thus be necessary for the correct conformation or orientation of cytochrome c1 in the mitochondrial inner membrane. Accumulation of cytochrome c1 protein in mitochondria is dependent on the abailability of heme. This was shown with a delta-aminolevulinic acid synthetase-deficient yeast mutant which lacks heme and any light-absorbing peaks attributable to cytochromes. Mitochondria from mutant cells grown without added delta-aminolevulinic acid contained at least 20 times less protein immunoprecipitable by cytochrome c1-antisera than mitochondria from cells grown in the presence of the heme precursor. Similarly, the respiration-deficient promitochondria of anaerobically grown wild type cells are almost completely devoid of material cross-reacting with cytochrome c1-antisera. A 105,000 X g supernatant of aerobically grown wild type cells contains a 29,000 dalton polypeptide that is precipitated by cytochrome c1-antiserum but not by nonimmune serum. This polypeptide is also present in high speed supernatants from the heme-deficient mutant or from anaerobically gorwn wild type cells. The possible identity of this polypeptide with soluble apocytochrome c1 is being investigated."} {"id": "PMID:178653", "title": "Regulation of glycogen metabolism in astrocytoma and neuroblastoma cells in culture.", "content": "The regulation of glycogen metabolism in C-6 astrocytoma and C-1300 neuroblastoma cells in culture has been investigated. Two modes of control of glycogen metabolism appear to be operative. The regulation of intracellular glycogen concentrations and the predominant forms of glycogen phosphorylase and glycogen synthase vary with (a) the available energy supply, and (b) altered intracellular concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Both cell lines respond to glucose in the medium; when glucose levels are high, glycogen is synthesized, glycogen phosphorylase a decreases, and glycogen synthase a increases. When glucose in the medium decreases to a critical level, the phosphorylase a increases and glycogen concentrations in the cells decrease in aprallel with the medium glucose. The critical glucose concentration is 2.5 mM for the astrocytoma cells and 4 mM for the neuroblastoma cells. Insulin promotes the conversion of phosphorylase to the b form and synthase to the a form in both cell lines. All of these changes occur without alteration in the intracellular cyclic AMP concentrations. When cyclic AMP concentrations are increased in either cell line, phosphorylase a is increased, synthase a is decreased, and glycogen concentrations decrease. Isobutyl methylxanthine is effective in promoting glycogenolysis in both cell lines. Norepinephrine is effective with the astrocytoma cells, and prostaglandin E1 is effective with the neuroblastoma cells.", "contents": "Regulation of glycogen metabolism in astrocytoma and neuroblastoma cells in culture. The regulation of glycogen metabolism in C-6 astrocytoma and C-1300 neuroblastoma cells in culture has been investigated. Two modes of control of glycogen metabolism appear to be operative. The regulation of intracellular glycogen concentrations and the predominant forms of glycogen phosphorylase and glycogen synthase vary with (a) the available energy supply, and (b) altered intracellular concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Both cell lines respond to glucose in the medium; when glucose levels are high, glycogen is synthesized, glycogen phosphorylase a decreases, and glycogen synthase a increases. When glucose in the medium decreases to a critical level, the phosphorylase a increases and glycogen concentrations in the cells decrease in aprallel with the medium glucose. The critical glucose concentration is 2.5 mM for the astrocytoma cells and 4 mM for the neuroblastoma cells. Insulin promotes the conversion of phosphorylase to the b form and synthase to the a form in both cell lines. All of these changes occur without alteration in the intracellular cyclic AMP concentrations. When cyclic AMP concentrations are increased in either cell line, phosphorylase a is increased, synthase a is decreased, and glycogen concentrations decrease. Isobutyl methylxanthine is effective in promoting glycogenolysis in both cell lines. Norepinephrine is effective with the astrocytoma cells, and prostaglandin E1 is effective with the neuroblastoma cells."} {"id": "PMID:178654", "title": "Termination of procollagen chain synthesis by puromycin. Evidence that assembly and secretion require a COOH-terminal extension.", "content": "Embryonic chick fibroblasts were incubated with [14C]proline and puromycin in the low concentrations of 1 to 3 mug/ml. The molecular weight of the synthesized procollagen chains, as measured by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, was progressively reduced by increasing concentrations of puromycin in this range. For example, at 3 mug/ml the great majority of the [14C]proline was contained in procollagen chains having an average molecular weight of about 95,000 instead of the control value of 125,000. Associated with this decrease in molecular weight there was a marked decrease in the incorporation of cysteine although [14C]proline incorporation was relatively unaffedted. Disulfide bond formation was drastically inhibited as was triple helix formation as measured by resistance of the procollagen to pepsin digestion. Although the shortened procollagen chains were of normal hydroxyproline content, they nevertheless were secreted much more slowly than normal procollagen. Based upon these findings, we postulate that: (a) low concentrations of puromycin terminate procollagen chains before a COOH-terminal extension is completed, (b) these COOH-terminal extensions are required for normal assembly of the three individual procollagen chains and for triple helix formation, and (c) only assembled, triple helical procollagen molecules are selected for normal secretion.", "contents": "Termination of procollagen chain synthesis by puromycin. Evidence that assembly and secretion require a COOH-terminal extension. Embryonic chick fibroblasts were incubated with [14C]proline and puromycin in the low concentrations of 1 to 3 mug/ml. The molecular weight of the synthesized procollagen chains, as measured by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, was progressively reduced by increasing concentrations of puromycin in this range. For example, at 3 mug/ml the great majority of the [14C]proline was contained in procollagen chains having an average molecular weight of about 95,000 instead of the control value of 125,000. Associated with this decrease in molecular weight there was a marked decrease in the incorporation of cysteine although [14C]proline incorporation was relatively unaffedted. Disulfide bond formation was drastically inhibited as was triple helix formation as measured by resistance of the procollagen to pepsin digestion. Although the shortened procollagen chains were of normal hydroxyproline content, they nevertheless were secreted much more slowly than normal procollagen. Based upon these findings, we postulate that: (a) low concentrations of puromycin terminate procollagen chains before a COOH-terminal extension is completed, (b) these COOH-terminal extensions are required for normal assembly of the three individual procollagen chains and for triple helix formation, and (c) only assembled, triple helical procollagen molecules are selected for normal secretion."} {"id": "PMID:178655", "title": "Thermodynamic and EPR characteristics of two ferredoxin-type iron-sulfur centers in the succinate-ubiquinone reductase segment of the respiratory chain.", "content": "Two distinct ferredosin-type iron-sulfur centers (designated as Centers S-1 and S-2) are present in the soulble succinate dehydrogenase in approximately equivalent concentrations to that of bound flavin. Both Centers S-1 and S-2 exhibit electron paramagnetic resonance absorbance in the reduced state at the same magnetic field (gz = 2.03, gy = 1.93, and gx = 1.91) with similar line shape. Center S-2 is reducible only chemically with dithionite and remains oxidized under physiological conditions. Thus, its functional role is unknown; however, thermodynamic and EPR characterization of this iron-sulfur center has revealed important molecular events related to this dehydrogenase. The midpoint potentials of Centers S-1 and S-2 determined in the soluble succinate dehydrogenase preparations are -5 +/- 15 mV and -400 +/- 15 mV, respectively, while corresponding midpoint potentials determined in particulate preparations, such as succinate-cytochrome c reductase or succinate-ubiquinone reductase, are 0 +/- 15 mV and -260 +/- 15 mV. Reconstitution of soluble succinate dehydrogenase with the cytochrome b-c1 complex is accompanied by a reversion of the Center S-I midpoint from -400 +/- 15 mV to -250 +/- 15 mV with a concomitant restoration of antimycin A-sensitive succinate-cytochrome c reductase activity. There observations indicate that, during the reconstitution process, Center S-I is restored to its original molecular environment. In the reconstitutively active succinate dehydrogenase, the relaxation time of Center S-2 is much shorter than that of S-1, thus Center S-2 spectra are well discernible only below 20 K (at 1 milliwatt of power), while the resonance absorbance of Center S-1 is detectable at higher temperatures and readily saturates below 15 K. Over a wide temperature range the power saturation of Center S-1 resonance absorbance is relieved by Center S-2 in the paramagnetic state, and the Center S-2 central resonance absorbance is broadened by Center S-1 spins, due to a spin-spin interaction between these centers. These observations indicate an adjacent location of these centers in the enzyme molecule. In reconstitutively inactive enzymes, subtle modification of the enzyme structure appears to shift the temperature dependence of Center S-2 relaxation to the higher temperature. Thus the EPR signals of Center S-2 are also detectable at higher temperature. In this system a splitting of the central peak of the Center S-2 spectrum due to spin-spin interaction was observed at extremely low temperatures, while this was not observed in reconstitutively active enzymes or in paritculate preparations. This spin-spin interaction phenomena of inactive enzymes disappeared upon chemical reactivation with concomitant appearance of the reconstitutive activity. These observations provide a close correlation between the molecular integrity of the enzyme and its physiological function.", "contents": "Thermodynamic and EPR characteristics of two ferredoxin-type iron-sulfur centers in the succinate-ubiquinone reductase segment of the respiratory chain. Two distinct ferredosin-type iron-sulfur centers (designated as Centers S-1 and S-2) are present in the soulble succinate dehydrogenase in approximately equivalent concentrations to that of bound flavin. Both Centers S-1 and S-2 exhibit electron paramagnetic resonance absorbance in the reduced state at the same magnetic field (gz = 2.03, gy = 1.93, and gx = 1.91) with similar line shape. Center S-2 is reducible only chemically with dithionite and remains oxidized under physiological conditions. Thus, its functional role is unknown; however, thermodynamic and EPR characterization of this iron-sulfur center has revealed important molecular events related to this dehydrogenase. The midpoint potentials of Centers S-1 and S-2 determined in the soluble succinate dehydrogenase preparations are -5 +/- 15 mV and -400 +/- 15 mV, respectively, while corresponding midpoint potentials determined in particulate preparations, such as succinate-cytochrome c reductase or succinate-ubiquinone reductase, are 0 +/- 15 mV and -260 +/- 15 mV. Reconstitution of soluble succinate dehydrogenase with the cytochrome b-c1 complex is accompanied by a reversion of the Center S-I midpoint from -400 +/- 15 mV to -250 +/- 15 mV with a concomitant restoration of antimycin A-sensitive succinate-cytochrome c reductase activity. There observations indicate that, during the reconstitution process, Center S-I is restored to its original molecular environment. In the reconstitutively active succinate dehydrogenase, the relaxation time of Center S-2 is much shorter than that of S-1, thus Center S-2 spectra are well discernible only below 20 K (at 1 milliwatt of power), while the resonance absorbance of Center S-1 is detectable at higher temperatures and readily saturates below 15 K. Over a wide temperature range the power saturation of Center S-1 resonance absorbance is relieved by Center S-2 in the paramagnetic state, and the Center S-2 central resonance absorbance is broadened by Center S-1 spins, due to a spin-spin interaction between these centers. These observations indicate an adjacent location of these centers in the enzyme molecule. In reconstitutively inactive enzymes, subtle modification of the enzyme structure appears to shift the temperature dependence of Center S-2 relaxation to the higher temperature. Thus the EPR signals of Center S-2 are also detectable at higher temperature. In this system a splitting of the central peak of the Center S-2 spectrum due to spin-spin interaction was observed at extremely low temperatures, while this was not observed in reconstitutively active enzymes or in paritculate preparations. This spin-spin interaction phenomena of inactive enzymes disappeared upon chemical reactivation with concomitant appearance of the reconstitutive activity. These observations provide a close correlation between the molecular integrity of the enzyme and its physiological function."} {"id": "PMID:178656", "title": "Thermodynamic and EPR characteristics of a HiPIP-type iron-sulfur center in the succinate dehydrogenase of the respiratory chain.", "content": "In addition to the two species of ferredoxin-type iron-sulfur centers (Centers S-1 and S-2), a third iron-sulfur center (Center S-3), which is paramagnetic in the oxidezed state analogous to the bacterial high potential iron-sulfur protein, has bwen detected in the reconstitutively active soluble succinate dehydrogenase preparation. Midpoint potential (at pH 7.4) of Center S-3 determined in a particulate succinate-cytochrome c reductase is +60 +/- 15 mV. In soluble form, Center S-3 becomes extremely labile towards oxygen or ferricyanide plus phenazine methosulfate similar to reconstitutive activity of the dehydrogenase. Thus, even freshly prepared reconstitutively active enzyme preparations show EPR spectra of Center S-3 which correspond approximately to 0.5 eq per flavin; in particulate preparations this component was found in a 1:1 ratio to flavin. All reconstitutively inactive dehydrogenase preparations that Center S-3 is an innate constituent of succinate dehydrogenase and plays an important role in mediating electrons from the flavoprotein subunit to most probably ubiquinone and then to the cytochrome chain.", "contents": "Thermodynamic and EPR characteristics of a HiPIP-type iron-sulfur center in the succinate dehydrogenase of the respiratory chain. In addition to the two species of ferredoxin-type iron-sulfur centers (Centers S-1 and S-2), a third iron-sulfur center (Center S-3), which is paramagnetic in the oxidezed state analogous to the bacterial high potential iron-sulfur protein, has bwen detected in the reconstitutively active soluble succinate dehydrogenase preparation. Midpoint potential (at pH 7.4) of Center S-3 determined in a particulate succinate-cytochrome c reductase is +60 +/- 15 mV. In soluble form, Center S-3 becomes extremely labile towards oxygen or ferricyanide plus phenazine methosulfate similar to reconstitutive activity of the dehydrogenase. Thus, even freshly prepared reconstitutively active enzyme preparations show EPR spectra of Center S-3 which correspond approximately to 0.5 eq per flavin; in particulate preparations this component was found in a 1:1 ratio to flavin. All reconstitutively inactive dehydrogenase preparations that Center S-3 is an innate constituent of succinate dehydrogenase and plays an important role in mediating electrons from the flavoprotein subunit to most probably ubiquinone and then to the cytochrome chain."} {"id": "PMID:178657", "title": "Biochemical and ultrastructural hepatic changes during vitamin B12 deficiency in animals and man.", "content": "Vitamin B12 deficiency has been shown to result in an increase in content and activity of the hepatic cytosolic enzymes of fatty acid synthesis. The present study demonstrated that ATP citrate lyase, an enzyme whose activity has been positively correlated with rates of fatty acid biosynthesis, also increased in the livers of B12-deficient animals. Total and specific activity of hepatic citrate synthase, an enzyme whose activity is unaffected by a variety of dietary and hormonal changes, also was found to be increased in the B12-deprived state. By contrast, the activity of hepatic succinate-cytochrome c reductase, a portion of a multicomponent enzyme complex synthesized in part within the mitochondria, was unchanged in B12 deficiency. Vitamin B12 deprivation resulted in an increase in hepatic mitochondrial cristae membranes in both animals and man. Histochemical and chemical analysis demonstrated increased glycogen in the liver cells from B12-deficient animals and man. Thus, in the livers from vitamin B12-deficient animals there is an increased activity of the otherwise highly constant Krebs cycle enzyme citrate synthase, and in both animals and man there are increased mitochondrial cristae membranes.", "contents": "Biochemical and ultrastructural hepatic changes during vitamin B12 deficiency in animals and man. Vitamin B12 deficiency has been shown to result in an increase in content and activity of the hepatic cytosolic enzymes of fatty acid synthesis. The present study demonstrated that ATP citrate lyase, an enzyme whose activity has been positively correlated with rates of fatty acid biosynthesis, also increased in the livers of B12-deficient animals. Total and specific activity of hepatic citrate synthase, an enzyme whose activity is unaffected by a variety of dietary and hormonal changes, also was found to be increased in the B12-deprived state. By contrast, the activity of hepatic succinate-cytochrome c reductase, a portion of a multicomponent enzyme complex synthesized in part within the mitochondria, was unchanged in B12 deficiency. Vitamin B12 deprivation resulted in an increase in hepatic mitochondrial cristae membranes in both animals and man. Histochemical and chemical analysis demonstrated increased glycogen in the liver cells from B12-deficient animals and man. Thus, in the livers from vitamin B12-deficient animals there is an increased activity of the otherwise highly constant Krebs cycle enzyme citrate synthase, and in both animals and man there are increased mitochondrial cristae membranes."} {"id": "PMID:178658", "title": "Differences in properties of cytosol and membrane-derived protein kinases.", "content": "Adenosine 3':5'-monophosphate-dependent protein kinase present in membrane fractions of bovine brain, heart, liver, and muscle was solubilized with Triton X-100. Certain properties of the membrane-derived enzyme were compared with those of two adenosine 3':5'-monophosphate-dependent protein kinases present in the cytosol fractions from each of the same tissues. The properties studied included chromatographic behavior on DEAE-cellulose columns, specificity with respect to substrate proteins, and sensitivity to NaCl and Triton X-100. The membrane-derived enzyme from each tissue had properties similar to those of the membrane-derived enzyme from each of the other tissues. Moreover, the cytosol enzymes from each tissue had properties similar to those of the corresponding enzymes in the cytosol from each of the other tissues. However, for any given tissue, the properties of the membrane-derived enzyme differed from those of the cytosol enzymes, possibly reflecting different functional roles for the membrane-bound and cytosol enzymes.", "contents": "Differences in properties of cytosol and membrane-derived protein kinases. Adenosine 3':5'-monophosphate-dependent protein kinase present in membrane fractions of bovine brain, heart, liver, and muscle was solubilized with Triton X-100. Certain properties of the membrane-derived enzyme were compared with those of two adenosine 3':5'-monophosphate-dependent protein kinases present in the cytosol fractions from each of the same tissues. The properties studied included chromatographic behavior on DEAE-cellulose columns, specificity with respect to substrate proteins, and sensitivity to NaCl and Triton X-100. The membrane-derived enzyme from each tissue had properties similar to those of the membrane-derived enzyme from each of the other tissues. Moreover, the cytosol enzymes from each tissue had properties similar to those of the corresponding enzymes in the cytosol from each of the other tissues. However, for any given tissue, the properties of the membrane-derived enzyme differed from those of the cytosol enzymes, possibly reflecting different functional roles for the membrane-bound and cytosol enzymes."} {"id": "PMID:178659", "title": "6-phosphofructokinase (pyrophosphate). Properties of the enzyme from Entamoeba histolytica and its reaction mechanism.", "content": "The inorganic pyrophosphate-requiring 6-phosphofructokinase of Entamoeba histolytica has been further investigated. The molecular weight of the enzyme is approximately 83,000 and its isoelectric point occurs at pH 5.8 to 6.0. The divalent cation requirement for reaction was explored. In the direction of fructose 6-phosphate formation half-maximal rate required 500 muM magnesium ion; in the direction of fructose bisphosphate formation 8 muM magnesium ion sufficed. ATP, PPi, polyphosphate, acetyl phosphate, or carbamyl phosphate cannot replace PPi as phosphate donor for the conversion of fructose 6-phosphate to fructose bisphosphate. In the direction of fructose 6-phosphate formation arsenate can replace orthophosphate. Isotope exchange studies indicate that little or no exchange occurs between Pi and PPi or between fructose 6-phosphate and fructose bisphosphate in the absence of a third substrate. These findings appear to rule out phosphoenzyme formation and a ping-pong reaction mechanism. PPi, Pi, and fructose bisphosphate are competitive inhibitors of fructose bisphosphate, PPi, and fructose 6-phosphate, respectively. This argues against an ordered mechanism and suggests a random mechanism. Fructose 6-phosphate and Pi were noncompetitive with respect to each other indicating the formation of a dead end complex. These product inhibition relationships are in accord with a Random Bi Bi mechanism.", "contents": "6-phosphofructokinase (pyrophosphate). Properties of the enzyme from Entamoeba histolytica and its reaction mechanism. The inorganic pyrophosphate-requiring 6-phosphofructokinase of Entamoeba histolytica has been further investigated. The molecular weight of the enzyme is approximately 83,000 and its isoelectric point occurs at pH 5.8 to 6.0. The divalent cation requirement for reaction was explored. In the direction of fructose 6-phosphate formation half-maximal rate required 500 muM magnesium ion; in the direction of fructose bisphosphate formation 8 muM magnesium ion sufficed. ATP, PPi, polyphosphate, acetyl phosphate, or carbamyl phosphate cannot replace PPi as phosphate donor for the conversion of fructose 6-phosphate to fructose bisphosphate. In the direction of fructose 6-phosphate formation arsenate can replace orthophosphate. Isotope exchange studies indicate that little or no exchange occurs between Pi and PPi or between fructose 6-phosphate and fructose bisphosphate in the absence of a third substrate. These findings appear to rule out phosphoenzyme formation and a ping-pong reaction mechanism. PPi, Pi, and fructose bisphosphate are competitive inhibitors of fructose bisphosphate, PPi, and fructose 6-phosphate, respectively. This argues against an ordered mechanism and suggests a random mechanism. Fructose 6-phosphate and Pi were noncompetitive with respect to each other indicating the formation of a dead end complex. These product inhibition relationships are in accord with a Random Bi Bi mechanism."} {"id": "PMID:178660", "title": "Studies on the role of cyclic guanosine 3':5'-monophosphate and extracellular Ca2+ in the regulation of glycogenolysis in rat liver cells.", "content": "Catecholamines increased guanosine 3':5'-monophosphate (cyclic GMP) accumulation by isolated rat liver cells. The increases in cyclic GMP due to 1.5 muM epinephrine, isoproterenol, or phenylephrine were blocked by phenoxybenzamine but not by propranolol. The possibility that cyclic GMP is involved in the glycogenolytic action of catecholamines seems unlikely since cyclic GMP accumulation is also elevated by carbachol, insulin, A23187, and to a lesser extent by glucagon. Furthermore, carbachol had little effect on glycogenolysis while insulin actually inhibited hepatic glycogenolysis. The rise in cyclic GMP due to carbachol was abolished by atropine and that due to all agents was markedly reduced by the omission of extracellular calcium. However, the glycogenolytic action of glucagon and catecholamines was only slightly inhibited by the omission of calcium. The only agent which was unable to stimulate glycogenolysis in calcium-free buffer was the divalent cation ionophore A23187. There was a drop in ATP content of liver cells during incubation in calcium-free buffer which was accompanied by an inhibition of glucagon-activated adenosine 3':5'-monophosphate (cyclic AMP) accumulation. The presence of calcium inhibited the rise in adenylate cyclase activity of lysed rat liver cells due to glucagon or isoproterenol but not that due to fluoride. These results suggest that the stimulation by catecholamines and glucagon of glycogenolysis is not mediated through cyclic GMP nor does it depend on the presence of extracellular calcium. Cyclic GMP accumulation was increased in liver cells by agents which either inhibit, have little affect, or accelerate glycogenolysis. The significance of elevations of cyclic GMP in rat liver cells remains to be established.", "contents": "Studies on the role of cyclic guanosine 3':5'-monophosphate and extracellular Ca2+ in the regulation of glycogenolysis in rat liver cells. Catecholamines increased guanosine 3':5'-monophosphate (cyclic GMP) accumulation by isolated rat liver cells. The increases in cyclic GMP due to 1.5 muM epinephrine, isoproterenol, or phenylephrine were blocked by phenoxybenzamine but not by propranolol. The possibility that cyclic GMP is involved in the glycogenolytic action of catecholamines seems unlikely since cyclic GMP accumulation is also elevated by carbachol, insulin, A23187, and to a lesser extent by glucagon. Furthermore, carbachol had little effect on glycogenolysis while insulin actually inhibited hepatic glycogenolysis. The rise in cyclic GMP due to carbachol was abolished by atropine and that due to all agents was markedly reduced by the omission of extracellular calcium. However, the glycogenolytic action of glucagon and catecholamines was only slightly inhibited by the omission of calcium. The only agent which was unable to stimulate glycogenolysis in calcium-free buffer was the divalent cation ionophore A23187. There was a drop in ATP content of liver cells during incubation in calcium-free buffer which was accompanied by an inhibition of glucagon-activated adenosine 3':5'-monophosphate (cyclic AMP) accumulation. The presence of calcium inhibited the rise in adenylate cyclase activity of lysed rat liver cells due to glucagon or isoproterenol but not that due to fluoride. These results suggest that the stimulation by catecholamines and glucagon of glycogenolysis is not mediated through cyclic GMP nor does it depend on the presence of extracellular calcium. Cyclic GMP accumulation was increased in liver cells by agents which either inhibit, have little affect, or accelerate glycogenolysis. The significance of elevations of cyclic GMP in rat liver cells remains to be established."} {"id": "PMID:178661", "title": "Studies on the poky mutant of eurospora crassa. Fingerprint analysis of mitochondrial ribosomal RNA.", "content": "Base sequence and methylation of mitochondrial ribosomal RNAs from wild type and poky strains of Neurospora crassa were compared to determine whether a mutational lesion exists in poky 19 S RNA. At the outset, new procedures were developed for the isolation of intact nucleic acids from Neurospora mitochondria based on the substitution of Ca2+ for Mg2+ in the isolation media to inhibit mitochondrial nuclease activity. Using these procedures, intact and highly purified 32P-labeled ribosomal RNAs were extracted from purified mitochondrial ribosomal subunits of wild type and poky and compared using three complementary fingerprinting systems: two-dimensional electrophoresis of T1 plus phosphatase digests and homochromatography of T1 and pancreatic RNase digests. In supplementary experiments, 32P-labeled wild type RNA was co-fingerprinted with 32P-labeled poky and ratios of 32P/33P radioactivity were determined in each fragment to detect possible differences in stoichiometry. In addition, levels and patterns of methylated nucleotides were compared using procedures based on in vivo labeling with [methyl-3H]methionine and [32P]orthophosphate. In all these experiments, no difference was detected between wild type and poky in base sequence or methylation of either 19 S or 25 S RNA. Levels of methylation of Neurospora mitochondrial ribosomal RNAs were extremely low (less than 0.1% of the nucleotides), and results based on fingerprint analysis and DEAE-cellulose chromatography of alkaline hydrolysates of the [3H]methyl-labeled RNA suggested that 25 S RNA contains two ribose methylations, while 19 S RNA contains no methylated nucleotides.", "contents": "Studies on the poky mutant of eurospora crassa. Fingerprint analysis of mitochondrial ribosomal RNA. Base sequence and methylation of mitochondrial ribosomal RNAs from wild type and poky strains of Neurospora crassa were compared to determine whether a mutational lesion exists in poky 19 S RNA. At the outset, new procedures were developed for the isolation of intact nucleic acids from Neurospora mitochondria based on the substitution of Ca2+ for Mg2+ in the isolation media to inhibit mitochondrial nuclease activity. Using these procedures, intact and highly purified 32P-labeled ribosomal RNAs were extracted from purified mitochondrial ribosomal subunits of wild type and poky and compared using three complementary fingerprinting systems: two-dimensional electrophoresis of T1 plus phosphatase digests and homochromatography of T1 and pancreatic RNase digests. In supplementary experiments, 32P-labeled wild type RNA was co-fingerprinted with 32P-labeled poky and ratios of 32P/33P radioactivity were determined in each fragment to detect possible differences in stoichiometry. In addition, levels and patterns of methylated nucleotides were compared using procedures based on in vivo labeling with [methyl-3H]methionine and [32P]orthophosphate. In all these experiments, no difference was detected between wild type and poky in base sequence or methylation of either 19 S or 25 S RNA. Levels of methylation of Neurospora mitochondrial ribosomal RNAs were extremely low (less than 0.1% of the nucleotides), and results based on fingerprint analysis and DEAE-cellulose chromatography of alkaline hydrolysates of the [3H]methyl-labeled RNA suggested that 25 S RNA contains two ribose methylations, while 19 S RNA contains no methylated nucleotides."} {"id": "PMID:178662", "title": "Acetate kinase from Veillonella alcalescens. Regulation of enzyme activity by succinate and substrates.", "content": "Acetate kinase of Veillonella alcalescens has been shown to be highly regulated enzyme exhibiting two levels of control: the requirement for succinate as a heterotropic allosteric effector, and cooperative binding at the substrate level. Succinate addition was necessary for enzymatic activity in both the direction of acyl phosphate synthesis and that of ATP synthesis. Control at the substrate level was apparent in the cooperative binding (Hill coefficients of 2) of acetyl phosphate, ATP, and ADP. Typical Michaelis kinetic data were observed for succinate (Ka = 20 mM for acetyl phosphate synthesis, 0.4 mM for ATP synthesis), acetate, and propionate. The primary effect of succinate was to increase the apparent Vmax of the enzymatic reaction for the variable substrates, ATP, ADP, and acetyl phosphate. The results are interpreted as evidence that, as a heterotropic effector of the acetate kinase reaction, succinate may regulate levels of propionyl-CoA (produced from propionyl phosphate by action of phosphotransacetylase), a compound required for the conversion of succinate to propionate. Acetase kinase has been shown to be a probable dimeric protein composed of two subunits of molecular weight 44,000 each.", "contents": "Acetate kinase from Veillonella alcalescens. Regulation of enzyme activity by succinate and substrates. Acetate kinase of Veillonella alcalescens has been shown to be highly regulated enzyme exhibiting two levels of control: the requirement for succinate as a heterotropic allosteric effector, and cooperative binding at the substrate level. Succinate addition was necessary for enzymatic activity in both the direction of acyl phosphate synthesis and that of ATP synthesis. Control at the substrate level was apparent in the cooperative binding (Hill coefficients of 2) of acetyl phosphate, ATP, and ADP. Typical Michaelis kinetic data were observed for succinate (Ka = 20 mM for acetyl phosphate synthesis, 0.4 mM for ATP synthesis), acetate, and propionate. The primary effect of succinate was to increase the apparent Vmax of the enzymatic reaction for the variable substrates, ATP, ADP, and acetyl phosphate. The results are interpreted as evidence that, as a heterotropic effector of the acetate kinase reaction, succinate may regulate levels of propionyl-CoA (produced from propionyl phosphate by action of phosphotransacetylase), a compound required for the conversion of succinate to propionate. Acetase kinase has been shown to be a probable dimeric protein composed of two subunits of molecular weight 44,000 each."} {"id": "PMID:178663", "title": "Characterization of a virion protein kinase as a virus-specified enzyme.", "content": "Antibodies which completely inhibited the enzymatic activity of the protein kinase associated with virions of frog virus were obtained by immunization of rabbits with the purified enzyme. This inhibition provided a specific probe for the frog virus protein kinase, since this antiserum had no inhibitory effect on a variety of other protein kinases, including the activity of uninfected cells, or the protein kinase associated with vesicular stomatitis virus or vaccinia virus cultivated in the same cell line as frog virus. The frog virus protein kinase was characterized as a virus-specified protein on the basis of the following observations: (a) the virion protein kinase was antigenically distinct from essentially all of the protein kinase expressed in uninfected cells; (b) following infection by frog virus more than a 15-fold increase was detected in the specific activity of intracellular protein kinase and most of this activity was antigenically related to the virion enzyme; (c) when frog virus was grown in cells derived from widely different species, the antigenic and biochemical specificities of the virion protein kinase remained identical; and (d) screening of cells infected with different temperature-sensitive mutants of frog virus indicated that certain viral mutants failed to synthesize this protein kinase when cultivated at the nonpermissive temperature.", "contents": "Characterization of a virion protein kinase as a virus-specified enzyme. Antibodies which completely inhibited the enzymatic activity of the protein kinase associated with virions of frog virus were obtained by immunization of rabbits with the purified enzyme. This inhibition provided a specific probe for the frog virus protein kinase, since this antiserum had no inhibitory effect on a variety of other protein kinases, including the activity of uninfected cells, or the protein kinase associated with vesicular stomatitis virus or vaccinia virus cultivated in the same cell line as frog virus. The frog virus protein kinase was characterized as a virus-specified protein on the basis of the following observations: (a) the virion protein kinase was antigenically distinct from essentially all of the protein kinase expressed in uninfected cells; (b) following infection by frog virus more than a 15-fold increase was detected in the specific activity of intracellular protein kinase and most of this activity was antigenically related to the virion enzyme; (c) when frog virus was grown in cells derived from widely different species, the antigenic and biochemical specificities of the virion protein kinase remained identical; and (d) screening of cells infected with different temperature-sensitive mutants of frog virus indicated that certain viral mutants failed to synthesize this protein kinase when cultivated at the nonpermissive temperature."} {"id": "PMID:178664", "title": "Skeletal alterations following irradiation for Wilms' tumor: with particular reference to scoliosis and kyphosis.", "content": "The roentgenographic changes in the axial skeleton after irradiation for Wilms' tumor were studied in eighty-one patients. In addition to the initial alterations found in the individual vertebrae within the field of irradiation, spinal deformity subsequently developed in fifty-nine patients (pure scoliosis in thirty-eight, kyphoscoliosis in nineteen, and pure kyphosis in two). Unitl the adolescent growth spurt these deformities tended to remain slight, but some progression did occur. In seven patients the scoliosis became severe enough to require spine fusion. A Milwaukee brace used in three patients failed to correct the curve. The trapezoidal shape of the vertebrae and scarring of the soft tissues within the concavity made correction difficult. Recognizable roentgenographic alterations failed to develop in twenty-two patients who, in general, were older and had received less irradiation. There appeared to be a correlation between the amount of irradiation and the severity of the spinal deformity (p is less than 0.05) and between the age of irradiation and the amount of deformity (p is less than 0.02).", "contents": "Skeletal alterations following irradiation for Wilms' tumor: with particular reference to scoliosis and kyphosis. The roentgenographic changes in the axial skeleton after irradiation for Wilms' tumor were studied in eighty-one patients. In addition to the initial alterations found in the individual vertebrae within the field of irradiation, spinal deformity subsequently developed in fifty-nine patients (pure scoliosis in thirty-eight, kyphoscoliosis in nineteen, and pure kyphosis in two). Unitl the adolescent growth spurt these deformities tended to remain slight, but some progression did occur. In seven patients the scoliosis became severe enough to require spine fusion. A Milwaukee brace used in three patients failed to correct the curve. The trapezoidal shape of the vertebrae and scarring of the soft tissues within the concavity made correction difficult. Recognizable roentgenographic alterations failed to develop in twenty-two patients who, in general, were older and had received less irradiation. There appeared to be a correlation between the amount of irradiation and the severity of the spinal deformity (p is less than 0.05) and between the age of irradiation and the amount of deformity (p is less than 0.02)."} {"id": "PMID:178665", "title": "Skeletal immaturity in Perthes' disease.", "content": "Skeletal age was estimated by examination of radiographs of the carpus in 182 children suffering from Perthes' disease after the reliability of the Greulich and Pyle Atlas had been checked for a control group of British children. A striking tendency to delayed skeletal maturation was shown in the children with Perthes' disease. This trait was also found in ninety-three unaffected siblings of the patients. The velocity of skeletal ageing as the disease progressed was estimated. In some patients the carpal skeleton failed to mature at all for periods of up to three years and the term \"skeletal standstill\" is applied to this phenomenon. The significance of these findings is discussed and it is suggested that the maturation defect may have aetiological significance.", "contents": "Skeletal immaturity in Perthes' disease. Skeletal age was estimated by examination of radiographs of the carpus in 182 children suffering from Perthes' disease after the reliability of the Greulich and Pyle Atlas had been checked for a control group of British children. A striking tendency to delayed skeletal maturation was shown in the children with Perthes' disease. This trait was also found in ninety-three unaffected siblings of the patients. The velocity of skeletal ageing as the disease progressed was estimated. In some patients the carpal skeleton failed to mature at all for periods of up to three years and the term \"skeletal standstill\" is applied to this phenomenon. The significance of these findings is discussed and it is suggested that the maturation defect may have aetiological significance."} {"id": "PMID:178667", "title": "Developmental changes in mitochondria during the transition into lactation in the mouse mammary gland. II. Membrane marker enzymes and membrane ultrastructure.", "content": "The activity of cytochrome oxidase (an inner mitochondrial membrane marker) in mouse mammary gland homogenates was found to increase five- to sixfold from late pregnancy to day 8 of lactation, while that of monoamine oxidase (an outer membrane marker) increased only about 25%. The specific activity of cytochrome oxidase in the isolated mitochondria decreased slightly over the same period while the specific activity of monoamine oxidase decreased fivefold. This reflects the fact that both cytochrome oxidase and mitochondrial protein are increasing at a much greater rate than is monoamine oxidase activity. Mixing experiments preclude the possibility that the release or removal of an inhibitor or stimulator produces the changes in enzymatic activity. The cytochrome oxidase to monoamine oxidase ratio was followed throughout the pregnancy-lactation cycle in total mammary homogenates, isolated mammary parenchymal cells, and isolated mammary mitochondria. In each preparation the pattern was the same with little change in the ratio until late pregnancy; and then a three- to fourfold increase occurred and the values reached a maximum by day 8 of lactation. These experiments were interpreted as demonstrating that the observed enzymatic changes are reflective of alterations in the mitochondria of the mammary parenchymal cell population. Electron micrographs of mid-pregnant and mid-lactating mammary parenchymal cells in situ were prepared, and distinct changes in the mitochondrial morphology noted. The most significant and obvious change is the large increase in the number of inner membrane cristae and an increase in matrix density in the lactating gland cell. Therefore, both enzymatic and morphological studies support the concept of an expansion of the mitochondrial inner membrane during presecretory differentiation in the mouse mammary parenchymal cell.", "contents": "Developmental changes in mitochondria during the transition into lactation in the mouse mammary gland. II. Membrane marker enzymes and membrane ultrastructure. The activity of cytochrome oxidase (an inner mitochondrial membrane marker) in mouse mammary gland homogenates was found to increase five- to sixfold from late pregnancy to day 8 of lactation, while that of monoamine oxidase (an outer membrane marker) increased only about 25%. The specific activity of cytochrome oxidase in the isolated mitochondria decreased slightly over the same period while the specific activity of monoamine oxidase decreased fivefold. This reflects the fact that both cytochrome oxidase and mitochondrial protein are increasing at a much greater rate than is monoamine oxidase activity. Mixing experiments preclude the possibility that the release or removal of an inhibitor or stimulator produces the changes in enzymatic activity. The cytochrome oxidase to monoamine oxidase ratio was followed throughout the pregnancy-lactation cycle in total mammary homogenates, isolated mammary parenchymal cells, and isolated mammary mitochondria. In each preparation the pattern was the same with little change in the ratio until late pregnancy; and then a three- to fourfold increase occurred and the values reached a maximum by day 8 of lactation. These experiments were interpreted as demonstrating that the observed enzymatic changes are reflective of alterations in the mitochondria of the mammary parenchymal cell population. Electron micrographs of mid-pregnant and mid-lactating mammary parenchymal cells in situ were prepared, and distinct changes in the mitochondrial morphology noted. The most significant and obvious change is the large increase in the number of inner membrane cristae and an increase in matrix density in the lactating gland cell. Therefore, both enzymatic and morphological studies support the concept of an expansion of the mitochondrial inner membrane during presecretory differentiation in the mouse mammary parenchymal cell."} {"id": "PMID:178668", "title": "Hepatic organelle interaction. IV. Mechanism of succinate enhancement of formaldehyde accumulation from endoplasmic reticulum N-dealkylations.", "content": "Further evidence for organelle interaction during drug metabolism by the liver is presented. The apparent stimulation by succinate of formaldehyde accumulation in the medium, which was reported to occur with liver slices and homogenates as well as with mitochondria plus microsomes, has been shown to be the result of succinate inhibition of mitochondrial aldehyde dehydrogenase. The mechanism of succinate inhibition is shown to be by reverse electron transport, and an increase in the NADH to NAD+ ratio in the mitochondria; the aldehyde dehydrogenase requires the oxidized form of the pyridine nucleotide as its cofactor. Studies on in vitro N-demethylation by liver microsomes and endoplasmic reticulum segments which cosediment with the mitochondria indicate that formaldehyde produced by the mixed function oxidase is handled differently from formaldehyde added to the medium. The latter is mainly retained in the medium containing 5 mM semicarbazide, while the generated formaldehyde is more than 50% consumed by the mitochondria. Electron microscopy has indicated that the microsomes and the endoplasmic reticulum fragments have a tendency to align themselves close to the mitochondria when present in the same medium. Consequently, it is possible that formaldehyde released to the medium adjacent to the mitochondria, as by N-demethylation, would be exposed to semicarbazide for shorter periods than that added directly to the medium. In agreement with this suggestion, complexing of formaldehyde with semicarbazide was observed spectroscopically not to be an extremely rapid reaction even at 37 degrees C. This is believed to be the reason for the greater extent of consumption of formaldehyde generated by the endoplasmic reticulum.", "contents": "Hepatic organelle interaction. IV. Mechanism of succinate enhancement of formaldehyde accumulation from endoplasmic reticulum N-dealkylations. Further evidence for organelle interaction during drug metabolism by the liver is presented. The apparent stimulation by succinate of formaldehyde accumulation in the medium, which was reported to occur with liver slices and homogenates as well as with mitochondria plus microsomes, has been shown to be the result of succinate inhibition of mitochondrial aldehyde dehydrogenase. The mechanism of succinate inhibition is shown to be by reverse electron transport, and an increase in the NADH to NAD+ ratio in the mitochondria; the aldehyde dehydrogenase requires the oxidized form of the pyridine nucleotide as its cofactor. Studies on in vitro N-demethylation by liver microsomes and endoplasmic reticulum segments which cosediment with the mitochondria indicate that formaldehyde produced by the mixed function oxidase is handled differently from formaldehyde added to the medium. The latter is mainly retained in the medium containing 5 mM semicarbazide, while the generated formaldehyde is more than 50% consumed by the mitochondria. Electron microscopy has indicated that the microsomes and the endoplasmic reticulum fragments have a tendency to align themselves close to the mitochondria when present in the same medium. Consequently, it is possible that formaldehyde released to the medium adjacent to the mitochondria, as by N-demethylation, would be exposed to semicarbazide for shorter periods than that added directly to the medium. In agreement with this suggestion, complexing of formaldehyde with semicarbazide was observed spectroscopically not to be an extremely rapid reaction even at 37 degrees C. This is believed to be the reason for the greater extent of consumption of formaldehyde generated by the endoplasmic reticulum."} {"id": "PMID:178666", "title": "The Klippel-Trenaunay syndrome. A case report and review.", "content": "The Klippel-Trenaunay syndrome presents with a vascular nevus extending over an entire extremity, ipsilateral varicose veins dating from infancy and hypertrophy of all the tissues of the affected limb. This paper illustrates the problems that can be encountered in the management of this disorder. Congenital angiodysplasias should be suspected in all young individuals presenting with unilateral varicose veins. We recommend that modern methods of investigation be used in these cases to precisely define the anatomic pathology. In this manner, the appropriate treatment may be tailored to the patient's specific disorder.", "contents": "The Klippel-Trenaunay syndrome. A case report and review. The Klippel-Trenaunay syndrome presents with a vascular nevus extending over an entire extremity, ipsilateral varicose veins dating from infancy and hypertrophy of all the tissues of the affected limb. This paper illustrates the problems that can be encountered in the management of this disorder. Congenital angiodysplasias should be suspected in all young individuals presenting with unilateral varicose veins. We recommend that modern methods of investigation be used in these cases to precisely define the anatomic pathology. In this manner, the appropriate treatment may be tailored to the patient's specific disorder."} {"id": "PMID:178669", "title": "Effects of nuclease and protease digestion on the ultrastructure of Paramecium basal bodies.", "content": "The action of deoxyribonuclease, ribonuclease, perchloric acid, and pronase on the fine structure of basal bodies of sectioned Paramecium was observed as part of a more extensive autoradiographic electron microscope analysis directed toward the problem of basal body DNA. DNase was found to have no detectable effect on basal body fine structure. Pronase first solubilized the linkers and C tubules of the triplets, then attacked the protein portion of the axosome, a localized portion of the ciliary axoneme adjacent to the distal end of the basal body, the rim fiber, and newly described lumen spiral complex. Prolonged pronase treatment disrupted the remaining microtubular elements, basal body plates, and cartwheel. RNase removed material from the axosome and the lumen complex, a conspicuous structure occupying the central portion of the basal body and consisting of a twisted or looped 90-A diam fiber or, more probably, pair of fibers, in association with large, dense granules. The apparent removal of both RNA and protein from this basal body structure by either of the two corresponding enzymes suggests an unusual organization of the two components. Observations from this and other laboratories suggest that the basal body RNA is single stranded. Its function is unknown but alternatives are discussed.", "contents": "Effects of nuclease and protease digestion on the ultrastructure of Paramecium basal bodies. The action of deoxyribonuclease, ribonuclease, perchloric acid, and pronase on the fine structure of basal bodies of sectioned Paramecium was observed as part of a more extensive autoradiographic electron microscope analysis directed toward the problem of basal body DNA. DNase was found to have no detectable effect on basal body fine structure. Pronase first solubilized the linkers and C tubules of the triplets, then attacked the protein portion of the axosome, a localized portion of the ciliary axoneme adjacent to the distal end of the basal body, the rim fiber, and newly described lumen spiral complex. Prolonged pronase treatment disrupted the remaining microtubular elements, basal body plates, and cartwheel. RNase removed material from the axosome and the lumen complex, a conspicuous structure occupying the central portion of the basal body and consisting of a twisted or looped 90-A diam fiber or, more probably, pair of fibers, in association with large, dense granules. The apparent removal of both RNA and protein from this basal body structure by either of the two corresponding enzymes suggests an unusual organization of the two components. Observations from this and other laboratories suggest that the basal body RNA is single stranded. Its function is unknown but alternatives are discussed."} {"id": "PMID:178670", "title": "Purine and phosphoribosylpyrophosphate synthesis in differentiating murine virus-induced erythroleukemic cells in vitro.", "content": "Phosphoribosylpyrophosphate synthetase activity was determined in Friend virus-inducted erythroleukemic cells in culture, stimulated to differentiate in the presence of dimethylsulfoxide. The activity of phosphoribosylpyrophosphate synthetase did not decrease in cells which had acquired the specialized function of hemoglobin synthesis, nor was the phosphoribosylpyrophosphate content of untreated erythroleukemic cells significantly different from that of cultures exposed to dimethylsulfoxide for 96 hours. However, the rate of the early steps of de novo purine biosynthesis as measured by the incorporation of [1-14C] glycine and [1-14C] formate into formyglycinamide ribonucleotide, was significantly lower in differentiating cell cultures. The addition of glutamine or ammonia increased glycine incorporation of control cultures, but failed to do so in treated cultures. In the course of the normal development of erythrocytes in vivo, phosphoribosylpyrophosphate synthetase activity is preserved, while the capacity to synthesize purines de novo is lost, as is the activity of the phosphoribosyl-l-amine synthesizing enzymes. Our present study suggests that the rate of de novo purine biosynthesis in this erythroleukemic cell line is not limited by the availability of phosphoribosylphrophosphate, but rather by a decrease in the phosphoribosyl-l-amine synthesizing enzymes. These findings provide further evidence that during dimethylsulfoxide-stimulated erythroid maturation, the same regulatory mechanisms are operative as in normal cellular development, and that ammonia-dependent purine biosynthesis is subject to the same regulatory mechanisms as is glutamine-dependent biosynthesis.", "contents": "Purine and phosphoribosylpyrophosphate synthesis in differentiating murine virus-induced erythroleukemic cells in vitro. Phosphoribosylpyrophosphate synthetase activity was determined in Friend virus-inducted erythroleukemic cells in culture, stimulated to differentiate in the presence of dimethylsulfoxide. The activity of phosphoribosylpyrophosphate synthetase did not decrease in cells which had acquired the specialized function of hemoglobin synthesis, nor was the phosphoribosylpyrophosphate content of untreated erythroleukemic cells significantly different from that of cultures exposed to dimethylsulfoxide for 96 hours. However, the rate of the early steps of de novo purine biosynthesis as measured by the incorporation of [1-14C] glycine and [1-14C] formate into formyglycinamide ribonucleotide, was significantly lower in differentiating cell cultures. The addition of glutamine or ammonia increased glycine incorporation of control cultures, but failed to do so in treated cultures. In the course of the normal development of erythrocytes in vivo, phosphoribosylpyrophosphate synthetase activity is preserved, while the capacity to synthesize purines de novo is lost, as is the activity of the phosphoribosyl-l-amine synthesizing enzymes. Our present study suggests that the rate of de novo purine biosynthesis in this erythroleukemic cell line is not limited by the availability of phosphoribosylphrophosphate, but rather by a decrease in the phosphoribosyl-l-amine synthesizing enzymes. These findings provide further evidence that during dimethylsulfoxide-stimulated erythroid maturation, the same regulatory mechanisms are operative as in normal cellular development, and that ammonia-dependent purine biosynthesis is subject to the same regulatory mechanisms as is glutamine-dependent biosynthesis."} {"id": "PMID:178671", "title": "Turnover at nicotinamide adenine dinucleotide in cultures of human cells.", "content": "The rate of turnover of nicotinamide adenine dinucleotide (NAD) in the human cell line, D98/AH2, has been estimated by measuring the rates of entry into and exit from NAD molecules of 14C-adenine. In one set of experiments, cells were labeled by growth in medium containing 14C-adenine for six hours and then shifted to medium without labeled adenine. The loss of 14C-adenine from the adenine nucleotide and pyridine nucleotide pools was measured, and the data were analyzed using an analytical treatment which corrects for the relatively slow turnover of precursor pools. The loss of 14C-adenine from the NAD pool and from the precursor ATP pool could be related to the absolute rate of NAD breakdown. Under the experimental conditions used, the rate of NAD turnover ranged from 83,000 to 126,000 molecules per second per cell. In a complementary experiment cells were grown in the presence of unlabeled adenine, then shifted into medium containing 14C-adenine and the rate of entry of 14C-adenine into adenine and pyridine nucleotides was measured. The data were treated using a similar analysis to relate the rate of entry of 14C-adenine into NAD and the precursor ATP pools to the absolute turnover rate of NAD. This analysis gave a value for NAD turnover of 78,000 molecules per second per cell in excellent agreement with results from the pulse-chase experiments. The results from both types of experiment indicate that within D98/AH2 cells the half-life of an intact NAD molecule is 60 +/- 18 minutes. Thus, in a human D98/AH2 cell growing with a generation time of 24 hours, NAD is turning over at twice the rate found in Escherichia coli with a generation time of half an hour.", "contents": "Turnover at nicotinamide adenine dinucleotide in cultures of human cells. The rate of turnover of nicotinamide adenine dinucleotide (NAD) in the human cell line, D98/AH2, has been estimated by measuring the rates of entry into and exit from NAD molecules of 14C-adenine. In one set of experiments, cells were labeled by growth in medium containing 14C-adenine for six hours and then shifted to medium without labeled adenine. The loss of 14C-adenine from the adenine nucleotide and pyridine nucleotide pools was measured, and the data were analyzed using an analytical treatment which corrects for the relatively slow turnover of precursor pools. The loss of 14C-adenine from the NAD pool and from the precursor ATP pool could be related to the absolute rate of NAD breakdown. Under the experimental conditions used, the rate of NAD turnover ranged from 83,000 to 126,000 molecules per second per cell. In a complementary experiment cells were grown in the presence of unlabeled adenine, then shifted into medium containing 14C-adenine and the rate of entry of 14C-adenine into adenine and pyridine nucleotides was measured. The data were treated using a similar analysis to relate the rate of entry of 14C-adenine into NAD and the precursor ATP pools to the absolute turnover rate of NAD. This analysis gave a value for NAD turnover of 78,000 molecules per second per cell in excellent agreement with results from the pulse-chase experiments. The results from both types of experiment indicate that within D98/AH2 cells the half-life of an intact NAD molecule is 60 +/- 18 minutes. Thus, in a human D98/AH2 cell growing with a generation time of 24 hours, NAD is turning over at twice the rate found in Escherichia coli with a generation time of half an hour."} {"id": "PMID:178672", "title": "Development of a clonal myogenic cell line with unusual biochemical properties.", "content": "The morphological, ultrastructural, biochemical and electrophysiological properties of B104-F, a clonal cell line derived from a nitrosoethylurea-induced neoplasm in a rat, were studied as a function of the growth phase of the culture. Cells in exponentially growing cultures are mononucleate and produce action potentials when stimulated electrically. Stationary phase cultures contain three types of cells: cells of the first type are mononucleate and have long processes containing microfilaments and many parallel microtubules; cells of the second type are mononucleate but contain no microtubules and few microfilaments; and cells of the third type have ultrastructural features typical of multinucleate, striated myotubes. Multinucleate cells generate action potentials with both sodium and calcium components and are depolarized by acetylcholine. The acetylcholine response is blocked by d-tubocurarine. The specific activity of creatine phosphokinase is nine times higher in stationary phase cultures than in exponentially growing ones while the myokinase specific activity is unchanged. The gamma-aminobutyric acid content of the cells is 3.5- to 26-fold higher in stationary phase than in exponentially growing cultures, depending on the degree of fusion of the culture. The properties of B104-F are discussed in relation to the properties of developing skeletal muscle and of central nervous system cell lines.", "contents": "Development of a clonal myogenic cell line with unusual biochemical properties. The morphological, ultrastructural, biochemical and electrophysiological properties of B104-F, a clonal cell line derived from a nitrosoethylurea-induced neoplasm in a rat, were studied as a function of the growth phase of the culture. Cells in exponentially growing cultures are mononucleate and produce action potentials when stimulated electrically. Stationary phase cultures contain three types of cells: cells of the first type are mononucleate and have long processes containing microfilaments and many parallel microtubules; cells of the second type are mononucleate but contain no microtubules and few microfilaments; and cells of the third type have ultrastructural features typical of multinucleate, striated myotubes. Multinucleate cells generate action potentials with both sodium and calcium components and are depolarized by acetylcholine. The acetylcholine response is blocked by d-tubocurarine. The specific activity of creatine phosphokinase is nine times higher in stationary phase cultures than in exponentially growing ones while the myokinase specific activity is unchanged. The gamma-aminobutyric acid content of the cells is 3.5- to 26-fold higher in stationary phase than in exponentially growing cultures, depending on the degree of fusion of the culture. The properties of B104-F are discussed in relation to the properties of developing skeletal muscle and of central nervous system cell lines."} {"id": "PMID:178673", "title": "Establishment in culture of a multihormone-secreting cell strain derived from the MtT/F4 rat pituitary tumor.", "content": "A clonal cell strain F4C1 has been established from the transplantable rat pituitary tumor MtT/F4 and has been maintained in continuous culture for two years. The cells grow with a population doubling time of 48 hours; the karyotype with a modal number of 39 chromosomes includes a pair of large metacentric marker chromosomes. F4C1 cells in culture produce growth hormone and prolactin but not adrenocorticotropin in contrast to the MtT/F4 tumor which secretes all three hormones in the host rat. The cloned cells lack specific receptors for thyrotropin-releasing hormone and do not respond to this agent with increased prolactin or decreased growth hormone production. Treatment with hydrocortisone results in a small increase in growth hormone and a small decrease in prolactin production. Tumors generated in rats from injected F4C1 cells secrete prolactin and growth hormone but not adrenocorticotropin. The results suggest that growth hormone and prolactin are produced by a single cell type in the MtT/F4 tumor.", "contents": "Establishment in culture of a multihormone-secreting cell strain derived from the MtT/F4 rat pituitary tumor. A clonal cell strain F4C1 has been established from the transplantable rat pituitary tumor MtT/F4 and has been maintained in continuous culture for two years. The cells grow with a population doubling time of 48 hours; the karyotype with a modal number of 39 chromosomes includes a pair of large metacentric marker chromosomes. F4C1 cells in culture produce growth hormone and prolactin but not adrenocorticotropin in contrast to the MtT/F4 tumor which secretes all three hormones in the host rat. The cloned cells lack specific receptors for thyrotropin-releasing hormone and do not respond to this agent with increased prolactin or decreased growth hormone production. Treatment with hydrocortisone results in a small increase in growth hormone and a small decrease in prolactin production. Tumors generated in rats from injected F4C1 cells secrete prolactin and growth hormone but not adrenocorticotropin. The results suggest that growth hormone and prolactin are produced by a single cell type in the MtT/F4 tumor."} {"id": "PMID:178674", "title": "Increased susceptibility of murine teratocarcinoma cells to Simian virus 40 and polyoma virus following treatment with 5-bromodeoxyuridine.", "content": "Cultures of the multipotential stem cell, embryonal carcinoma (EC), of a murine teratocarcinoma were treated with 5-bromodeoxyuridine (BrdU). Within 2-4 days at concentrations of 1-50 mugm/ml of BrdU, there was a marked change in the morphology of cells observed by light and electron microscopy. A comparison of the growth potential showed that for up to four days the BrdU-treated cultures were similar to untreated cultures. When these BrdU-treated cells were infected with Simian virus 40 (SV40) and polyoma virus (Py), there was an increase in susceptibility of the treated cells. The untreated embryonal carcinoma cells were refractory. These results suggest that BrdU modifies the embryonal carcinoma cells to allow infection with two DNA viruses.", "contents": "Increased susceptibility of murine teratocarcinoma cells to Simian virus 40 and polyoma virus following treatment with 5-bromodeoxyuridine. Cultures of the multipotential stem cell, embryonal carcinoma (EC), of a murine teratocarcinoma were treated with 5-bromodeoxyuridine (BrdU). Within 2-4 days at concentrations of 1-50 mugm/ml of BrdU, there was a marked change in the morphology of cells observed by light and electron microscopy. A comparison of the growth potential showed that for up to four days the BrdU-treated cultures were similar to untreated cultures. When these BrdU-treated cells were infected with Simian virus 40 (SV40) and polyoma virus (Py), there was an increase in susceptibility of the treated cells. The untreated embryonal carcinoma cells were refractory. These results suggest that BrdU modifies the embryonal carcinoma cells to allow infection with two DNA viruses."} {"id": "PMID:178675", "title": "Cellular responsiveness to stimulation in vitro: increased responsiveness to colony stimulating factor of bone marrow colony-forming cells treated with surface-active agents and cyclic 3'5' AMP.", "content": "Addition of low concentrations (10 ng/ml) of saponin or Tween 80 to stimulated cultures of normal mouse bone marrow in agar increased the number of granulocyte-macrophage colonies which developed. Addition of cyclic AMP or dibutyryl cyclic AMP in low concentration (10(-8) to 10(-10) M) also enhanced colony numbers although concentrations above 10(-5) M were inhibitory. enhancement was found when marrow cells were pre-treated with these agents and cultured in their absence. The agents did not stimulate colony development in the absence of colony-stimulating factor and enhancement of colony number occurred only in cultures containing a concentration of colony-stimulating factor which was sub-optimal in terms of maximum colony development. There was no indication of increased colony-stimulating factor production by treated marrow cells under the experimental conditions used to show colony enhancement. It was concluded that the agents caused an increased responsiveness of colony-forming cells to colony-stimulating factor.", "contents": "Cellular responsiveness to stimulation in vitro: increased responsiveness to colony stimulating factor of bone marrow colony-forming cells treated with surface-active agents and cyclic 3'5' AMP. Addition of low concentrations (10 ng/ml) of saponin or Tween 80 to stimulated cultures of normal mouse bone marrow in agar increased the number of granulocyte-macrophage colonies which developed. Addition of cyclic AMP or dibutyryl cyclic AMP in low concentration (10(-8) to 10(-10) M) also enhanced colony numbers although concentrations above 10(-5) M were inhibitory. enhancement was found when marrow cells were pre-treated with these agents and cultured in their absence. The agents did not stimulate colony development in the absence of colony-stimulating factor and enhancement of colony number occurred only in cultures containing a concentration of colony-stimulating factor which was sub-optimal in terms of maximum colony development. There was no indication of increased colony-stimulating factor production by treated marrow cells under the experimental conditions used to show colony enhancement. It was concluded that the agents caused an increased responsiveness of colony-forming cells to colony-stimulating factor."} {"id": "PMID:178676", "title": "Increased PRPP synthetase activity in cultured rat hepatoma cells containing mutations in the hypoxanthine-guanine phosphoribosyltransferase gene.", "content": "Nine independently derived clones of mutagenized rat hepatoma cells selected for resistance to 6-mercaptopurine (6-MP) or 6-thioguanine (6-ThioG) have been isolated. Each has severely reduced catalytic activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and seven of them possess significantly increased activities of phosphoribosylpyrophosphate (PRPP) synthetase. The degrees of elevations of PRPP synthetase activities do not correlate with the degrees of deficiencies of HPRT activities. The cells from one of these clones, 1020/12, posses 40% of the normal HPRT catalytic activity and overproduce purines. We have extensively examined the cells from this clone. Immunotration studies of 1020/12 cells indicate that there is a mutation in the structural gene for HPRT. Although they possess increased specific catalytic activities of the enzyme. PRPP synthetase, the catalytic parameters, heat stability, and isoelectric pH of PRPP synthetase from 1020/12 cells are indistinguishable from those of the enzyme from wild-type cells. The cause of purine overproduction by 1020/12 cells appears to be the elevated PRPP synthetase activity, rather than a PRPP \"sparing\" effect stemming from reduced HPRT activity. Support for this idea is provided by the observation that the complete loss of HPRT activity in a clone derived from 1020/12 cells does not further enhance the levels of PRPP synthetase or purine overproduction. We propose that the elevated levels of PRPP synthetase activity in these HPRT deficient cells result from a mutational event in the structural gene for HPRT, and that this causes the disruption of a previously undescribed regulatory function of this gene on the expression of the PRPP synthetase gene.", "contents": "Increased PRPP synthetase activity in cultured rat hepatoma cells containing mutations in the hypoxanthine-guanine phosphoribosyltransferase gene. Nine independently derived clones of mutagenized rat hepatoma cells selected for resistance to 6-mercaptopurine (6-MP) or 6-thioguanine (6-ThioG) have been isolated. Each has severely reduced catalytic activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and seven of them possess significantly increased activities of phosphoribosylpyrophosphate (PRPP) synthetase. The degrees of elevations of PRPP synthetase activities do not correlate with the degrees of deficiencies of HPRT activities. The cells from one of these clones, 1020/12, posses 40% of the normal HPRT catalytic activity and overproduce purines. We have extensively examined the cells from this clone. Immunotration studies of 1020/12 cells indicate that there is a mutation in the structural gene for HPRT. Although they possess increased specific catalytic activities of the enzyme. PRPP synthetase, the catalytic parameters, heat stability, and isoelectric pH of PRPP synthetase from 1020/12 cells are indistinguishable from those of the enzyme from wild-type cells. The cause of purine overproduction by 1020/12 cells appears to be the elevated PRPP synthetase activity, rather than a PRPP \"sparing\" effect stemming from reduced HPRT activity. Support for this idea is provided by the observation that the complete loss of HPRT activity in a clone derived from 1020/12 cells does not further enhance the levels of PRPP synthetase or purine overproduction. We propose that the elevated levels of PRPP synthetase activity in these HPRT deficient cells result from a mutational event in the structural gene for HPRT, and that this causes the disruption of a previously undescribed regulatory function of this gene on the expression of the PRPP synthetase gene."} {"id": "PMID:178677", "title": "The role of calcium in the inhibition of cAMP accumulation in epiphyseal cartilage cells exposed to physiological pressure.", "content": "A hydrostatic pressure of 60g/cm sq (0.85 psi) inhibits the accumulation of cAMP in cells isolated from the proliferative zone of chick-tibia epiphyseal cartilage. The following findings indicate that this effect is mediated by a translocation of calcium: (i) the pressure enhances the cellular uptake of radiocalcium; (ii) the pressure effect on cAMP can be simulated by the calcium-ionophore A23187; (iii) the effects of pressure and A23187 are non-additive; (iv) the pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-tetraacetic-acid (EGTA); (v) the particulate adenyl cyclase activity of the proliferative zone is susceptible to non-competitive calcium inhibition. Throughout this study cells from the hypertrophic zone of the same epiphyses were used as controls. In these cells the calcium uptake was enhanced by pressure, but the cAMP level was not affected by pressure, A23187 or EGTA. This change in responsiveness, which accompanies the maturation of the cartilage cells, was shown to be due to a decrease in the calcium-inhibition of adenylate cyclase.", "contents": "The role of calcium in the inhibition of cAMP accumulation in epiphyseal cartilage cells exposed to physiological pressure. A hydrostatic pressure of 60g/cm sq (0.85 psi) inhibits the accumulation of cAMP in cells isolated from the proliferative zone of chick-tibia epiphyseal cartilage. The following findings indicate that this effect is mediated by a translocation of calcium: (i) the pressure enhances the cellular uptake of radiocalcium; (ii) the pressure effect on cAMP can be simulated by the calcium-ionophore A23187; (iii) the effects of pressure and A23187 are non-additive; (iv) the pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-tetraacetic-acid (EGTA); (v) the particulate adenyl cyclase activity of the proliferative zone is susceptible to non-competitive calcium inhibition. Throughout this study cells from the hypertrophic zone of the same epiphyses were used as controls. In these cells the calcium uptake was enhanced by pressure, but the cAMP level was not affected by pressure, A23187 or EGTA. This change in responsiveness, which accompanies the maturation of the cartilage cells, was shown to be due to a decrease in the calcium-inhibition of adenylate cyclase."} {"id": "PMID:178678", "title": "The dynamics of antibody-induced redistribution of viral envelope antigens in the plasma membranes of avian tumour virus-infected chick embryo fibroblasts.", "content": "Avian tumour virus-infected chick embryo fibroblasts express new antigens, identical with the viral envelope antigens, in their plasma membranes. Electron-microscopic examination of carbon-platinum replicas of cells labelled with haemocyanin-marked antibody has shown the distribution of these antigens to be diffuse over the cell surface with an increased concentration on peripheral cell processes. However, antigen-antibody complexes (AAC), resulting from reaction with specific antibody, may be redistributed into a variety of patterns. Observation of the time course of antibody-induced antigen mobility revealed a rapid and a delayed phase of redistribution. During the rapid phase (10 min or less) some of the antigen-bearing cells reorganized AAC into patches, while the remainder maintained a diffuse distribution. A fraction of the cells with either diffuse or patchy distribution also redistributed AAC into a pattern of 'marginal redistribution (MR)', consisting of linear aggreagation of AAC, at the cell edge. During the 'late' phase of redistribution (after about 20 min), AAC began to condense into one or more foci of coalescence (FC) on each cell. As the number of cells with FC increased with time, the fraction of cells which were labelled decreased. Electron-microscopic observation of thin sections of ferritin-labelled specimens indicated that AAC were lost by endocytosis and that this process was probably related to FC formation. Inhibitors of oxidative phosphorylation, protein synthesis, RNA synthesis, or microtubule assembly had no significant effect on the patterns or the course of redistribution. Iodoacetic acid (IAA), which depletes cellular ATP, and cytochalasin B (CB), which is believed to depolymerize microfilaments, partially inhibited MR and completely prevented FC formation and endocytosis. Paradoxically, IAA or CB-treated cells lost AAC very rapidly by some alternate mechanism not involving FC formation but which may entail a centrifugal migration of complexes to the cell extremities during the process of AAC disposal.", "contents": "The dynamics of antibody-induced redistribution of viral envelope antigens in the plasma membranes of avian tumour virus-infected chick embryo fibroblasts. Avian tumour virus-infected chick embryo fibroblasts express new antigens, identical with the viral envelope antigens, in their plasma membranes. Electron-microscopic examination of carbon-platinum replicas of cells labelled with haemocyanin-marked antibody has shown the distribution of these antigens to be diffuse over the cell surface with an increased concentration on peripheral cell processes. However, antigen-antibody complexes (AAC), resulting from reaction with specific antibody, may be redistributed into a variety of patterns. Observation of the time course of antibody-induced antigen mobility revealed a rapid and a delayed phase of redistribution. During the rapid phase (10 min or less) some of the antigen-bearing cells reorganized AAC into patches, while the remainder maintained a diffuse distribution. A fraction of the cells with either diffuse or patchy distribution also redistributed AAC into a pattern of 'marginal redistribution (MR)', consisting of linear aggreagation of AAC, at the cell edge. During the 'late' phase of redistribution (after about 20 min), AAC began to condense into one or more foci of coalescence (FC) on each cell. As the number of cells with FC increased with time, the fraction of cells which were labelled decreased. Electron-microscopic observation of thin sections of ferritin-labelled specimens indicated that AAC were lost by endocytosis and that this process was probably related to FC formation. Inhibitors of oxidative phosphorylation, protein synthesis, RNA synthesis, or microtubule assembly had no significant effect on the patterns or the course of redistribution. Iodoacetic acid (IAA), which depletes cellular ATP, and cytochalasin B (CB), which is believed to depolymerize microfilaments, partially inhibited MR and completely prevented FC formation and endocytosis. Paradoxically, IAA or CB-treated cells lost AAC very rapidly by some alternate mechanism not involving FC formation but which may entail a centrifugal migration of complexes to the cell extremities during the process of AAC disposal."} {"id": "PMID:178679", "title": "The morphology of green hydra endosymbionts as influenced by host strain and host environment.", "content": "The ultrastructure of Chlorella-like algal endosymbionts from the Florida and English strains of green hydra was compared under different host feeding and photoperiodic regimes. Under standard conditions (host fed daily, 12-h photoperiod) the algae from the 2 strains exhibited considerable differences. The English symbionts had a pyrenoid, compact chloroplast membranes and vesiculated polyphosphate bodies. By comparison, Florida symbionts lacked a pyrenoid, had chloroplasts with less compact membranes and exhibited spherical polyphosphate bodies. When maintained in the dark, algae from English hydra lost their pyrenoids, showed great compaction of the chloroplast and developed large, shield-shaped, electron-dense bodies. In contrast, algae from Florida hosts did not exhibit gross ultrastructural modification. Reciprocal cross-transfers of symbionts were made by placing Florida algae in English aposymbiotic (algal-free) hosts and vice versa. After residence in Florida hosts, English symbionts appeared to undergo ultrastructural modifications resulting in a morphology indistinguishable from the native Florida symbionts. Florida algae showed no modifications resulting from residence in English hosts. It thus appears that the English symbiont has great morphological plasticity, as its structure is greatly modified depending upon the host in which it resides and the conditions under which the host is maintained. The results of these studies are discussed and compared with published accounts of free-living Chlorella and with reports dealing with other Chlorella symbionts.", "contents": "The morphology of green hydra endosymbionts as influenced by host strain and host environment. The ultrastructure of Chlorella-like algal endosymbionts from the Florida and English strains of green hydra was compared under different host feeding and photoperiodic regimes. Under standard conditions (host fed daily, 12-h photoperiod) the algae from the 2 strains exhibited considerable differences. The English symbionts had a pyrenoid, compact chloroplast membranes and vesiculated polyphosphate bodies. By comparison, Florida symbionts lacked a pyrenoid, had chloroplasts with less compact membranes and exhibited spherical polyphosphate bodies. When maintained in the dark, algae from English hydra lost their pyrenoids, showed great compaction of the chloroplast and developed large, shield-shaped, electron-dense bodies. In contrast, algae from Florida hosts did not exhibit gross ultrastructural modification. Reciprocal cross-transfers of symbionts were made by placing Florida algae in English aposymbiotic (algal-free) hosts and vice versa. After residence in Florida hosts, English symbionts appeared to undergo ultrastructural modifications resulting in a morphology indistinguishable from the native Florida symbionts. Florida algae showed no modifications resulting from residence in English hosts. It thus appears that the English symbiont has great morphological plasticity, as its structure is greatly modified depending upon the host in which it resides and the conditions under which the host is maintained. The results of these studies are discussed and compared with published accounts of free-living Chlorella and with reports dealing with other Chlorella symbionts."} {"id": "PMID:178680", "title": "Purification and characterization of commercial NADH and accompanying dehydrogenase inhibitors.", "content": "The anion-exchange chromatography of commercial NADH using a potassium bicarbonate solution as eluent yields highly pure NADH with good stability. Twelve compounds are also separated which act as dehydrogenase inhibitors. The main impurities are further characterized. The compound mainly responsible for residual optical density in commercial NADH preparations is probably a stereoisomer of NADH which is in reversible equilibrium with NADH at pH values in the range 5-7. A method of thin-layer chromatography, to check commercial NADH preparations for impurities, is described.", "contents": "Purification and characterization of commercial NADH and accompanying dehydrogenase inhibitors. The anion-exchange chromatography of commercial NADH using a potassium bicarbonate solution as eluent yields highly pure NADH with good stability. Twelve compounds are also separated which act as dehydrogenase inhibitors. The main impurities are further characterized. The compound mainly responsible for residual optical density in commercial NADH preparations is probably a stereoisomer of NADH which is in reversible equilibrium with NADH at pH values in the range 5-7. A method of thin-layer chromatography, to check commercial NADH preparations for impurities, is described."} {"id": "PMID:178682", "title": "Distribution of plasma glucagon immunoreactivity in a patient with suspected glucagonoma.", "content": "Gel filtration of plasma from a patient with a clinical syndrome of glucagonoma and a total plasma glucagon level of 2600 pg/ml, revealed the four glucagon immunoreactive fractions found in normal subjects. The total hyperglucagonemia observed was due to high levels of true glucagon and proglucagon moieties. The so-called \"big plasma glucagon\" (BPG) measured 190 pg/ml (normal average 113 +/- 79 pg/ml, Mean +/- SD, N = 10); the large glucagon immunoreactivity, LGI (9000 mol wt), measured 625 pg/ml (normal average 11 +/- 16 pg/ml); the true glucagon accounted for 1435 pg/ml (normal average 31 +/- 29 pg/ml); and the small glucagon immunoreactive fraction (approximately 2000 mol wt) measured 35 pg/ml (normal average 26 +/- 18 pg/ml). The high levels of LGI, considered a candidate for proglucagon, may reflect the increased secretory activity of the tumor.", "contents": "Distribution of plasma glucagon immunoreactivity in a patient with suspected glucagonoma. Gel filtration of plasma from a patient with a clinical syndrome of glucagonoma and a total plasma glucagon level of 2600 pg/ml, revealed the four glucagon immunoreactive fractions found in normal subjects. The total hyperglucagonemia observed was due to high levels of true glucagon and proglucagon moieties. The so-called \"big plasma glucagon\" (BPG) measured 190 pg/ml (normal average 113 +/- 79 pg/ml, Mean +/- SD, N = 10); the large glucagon immunoreactivity, LGI (9000 mol wt), measured 625 pg/ml (normal average 11 +/- 16 pg/ml); the true glucagon accounted for 1435 pg/ml (normal average 31 +/- 29 pg/ml); and the small glucagon immunoreactive fraction (approximately 2000 mol wt) measured 35 pg/ml (normal average 26 +/- 18 pg/ml). The high levels of LGI, considered a candidate for proglucagon, may reflect the increased secretory activity of the tumor."} {"id": "PMID:178683", "title": "The role of growth hormone and cortisone on glucose and gluconeogenic substrate regulation in fasted hypopituitary children.", "content": "Panhypopituitarism may be associated with spontaneous hypoglycemia and marked insulin sensitivity. Five children with both growth hormone (GH) and adrenocorticotrophin (ACTH) insufficiency were studied in three periods: a) on no therapy; b) during cortisone acetate; and c) during GH and cortisone acetate replacement. With total caloric restriction prior to therapy, all patients became hypoglycemic (109 +/- 18 leads to 37 +/- 3.5 mg/dl, mean +/- SEM) and ketonemic (beta-hydroxybutyrate 0.10 +/- 0.02 leads to 3.04 +/- 0.63 mM and acetoacetate 0.05 +/- .01 leads to 0.80 +/- 0.15 mM) within 30 hours. Glutamine and alanine concentrations fell with fasting (511 +/- 13 leads to 293 +/- 26 muM and 394 +/- 58 leads to 137 +/- 12 muM, respectively) but to levels lower than in normal children. However, only alanine was significantly lower (P less than 0.05). With cortisone plus GH therapy, fasting glycemia was improved (73 +/- 6 mg/dl) at 30 hours fasting and was associated with increased alanine and glutamine concentrations (206 +/- 28 muM and 448 +/- 40 muM, respectively) and less ketonemia (beta-hydroxybutyrate 1.13 +/- 0.39 mM). Cortisone therapy alone resulted in intermediate improvement of these values. Only combined therapy resulted in increased lactate and pyruvate concentrations, which fell to normal with fasting. Fasting urinary ammonia excretion was unchanged whereas urea nitrogen excretion decreased significantly with therapy. The responses to alanine infusions following each study period in one patient were normal. The glycemic response to iv glucose was similar during each study period; however, post-prandial and glucose-stimulated insulin responses were increased with cortisone and cortisone plus GH therapy. We suggest that the hypoglycemia observed in hypopituitary patients is a substrate-mediated phenomenon, and that cortisone and growth hormone replacement therapy improve fasting glucose homeostasis, increase circulating alanine and glutamine concentrations, and decrease hepatic gluconeogenesis. These effects may be mediated through an increase in fat catabolism.", "contents": "The role of growth hormone and cortisone on glucose and gluconeogenic substrate regulation in fasted hypopituitary children. Panhypopituitarism may be associated with spontaneous hypoglycemia and marked insulin sensitivity. Five children with both growth hormone (GH) and adrenocorticotrophin (ACTH) insufficiency were studied in three periods: a) on no therapy; b) during cortisone acetate; and c) during GH and cortisone acetate replacement. With total caloric restriction prior to therapy, all patients became hypoglycemic (109 +/- 18 leads to 37 +/- 3.5 mg/dl, mean +/- SEM) and ketonemic (beta-hydroxybutyrate 0.10 +/- 0.02 leads to 3.04 +/- 0.63 mM and acetoacetate 0.05 +/- .01 leads to 0.80 +/- 0.15 mM) within 30 hours. Glutamine and alanine concentrations fell with fasting (511 +/- 13 leads to 293 +/- 26 muM and 394 +/- 58 leads to 137 +/- 12 muM, respectively) but to levels lower than in normal children. However, only alanine was significantly lower (P less than 0.05). With cortisone plus GH therapy, fasting glycemia was improved (73 +/- 6 mg/dl) at 30 hours fasting and was associated with increased alanine and glutamine concentrations (206 +/- 28 muM and 448 +/- 40 muM, respectively) and less ketonemia (beta-hydroxybutyrate 1.13 +/- 0.39 mM). Cortisone therapy alone resulted in intermediate improvement of these values. Only combined therapy resulted in increased lactate and pyruvate concentrations, which fell to normal with fasting. Fasting urinary ammonia excretion was unchanged whereas urea nitrogen excretion decreased significantly with therapy. The responses to alanine infusions following each study period in one patient were normal. The glycemic response to iv glucose was similar during each study period; however, post-prandial and glucose-stimulated insulin responses were increased with cortisone and cortisone plus GH therapy. We suggest that the hypoglycemia observed in hypopituitary patients is a substrate-mediated phenomenon, and that cortisone and growth hormone replacement therapy improve fasting glucose homeostasis, increase circulating alanine and glutamine concentrations, and decrease hepatic gluconeogenesis. These effects may be mediated through an increase in fat catabolism."} {"id": "PMID:178684", "title": "The effect of medroxyprogesterone acetate on the pituitary-adrenal axis.", "content": "Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.", "contents": "The effect of medroxyprogesterone acetate on the pituitary-adrenal axis. Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary."} {"id": "PMID:178685", "title": "Pregnenolone, 17-OH-pregnenolone, and testosterone in plasma of patients with congenital adrenal hyperplasia.", "content": "Both pregnenolone and 17-OH-pregnenolone were found to be higher in the plasma of patients with poorly controlled congential adrenal hyperplasia than in normal subjects. The plasma levels of these precursor steroids were significantly correlated with urinary 17-ketosteroid and pregnanetriol excretion and with plasma testosterone. The mechanism where by plasma pregnenolone and 17-OH-pregnenolone levels are elevated in patients with 21-hydroxylase deficiency is unknown, but the phenomenon of product inhibition is suggested as a possible explanation. As 17-OH-pregnenolone in plasma is almost entirely of adrenal origin, its measurement promises to be useful in the management of patients with congenital adrenal hyperplasia. Acute stimulation with ACTH caused negligible changes in the plasma levels of pregnenolone and 17-OH-pregnenolone and failed to distinguish between overly, appropriately, and under-treated patients. However, following repeated stimulation with repository ACTH, the steroid levels rose. These findings indicate limited adrenal responsiveness to ACTH following chronic glucocorticoid treatment of congenital adrenal hyperplasia, even in under-treated patients, and suggest that normal precursor steroid levels in plasma and normal 17-ketosteroid and pregnanetriol excretion can only be achieved by the suppression of total steroidogenesis to less than that occurring in normal subjects.", "contents": "Pregnenolone, 17-OH-pregnenolone, and testosterone in plasma of patients with congenital adrenal hyperplasia. Both pregnenolone and 17-OH-pregnenolone were found to be higher in the plasma of patients with poorly controlled congential adrenal hyperplasia than in normal subjects. The plasma levels of these precursor steroids were significantly correlated with urinary 17-ketosteroid and pregnanetriol excretion and with plasma testosterone. The mechanism where by plasma pregnenolone and 17-OH-pregnenolone levels are elevated in patients with 21-hydroxylase deficiency is unknown, but the phenomenon of product inhibition is suggested as a possible explanation. As 17-OH-pregnenolone in plasma is almost entirely of adrenal origin, its measurement promises to be useful in the management of patients with congenital adrenal hyperplasia. Acute stimulation with ACTH caused negligible changes in the plasma levels of pregnenolone and 17-OH-pregnenolone and failed to distinguish between overly, appropriately, and under-treated patients. However, following repeated stimulation with repository ACTH, the steroid levels rose. These findings indicate limited adrenal responsiveness to ACTH following chronic glucocorticoid treatment of congenital adrenal hyperplasia, even in under-treated patients, and suggest that normal precursor steroid levels in plasma and normal 17-ketosteroid and pregnanetriol excretion can only be achieved by the suppression of total steroidogenesis to less than that occurring in normal subjects."} {"id": "PMID:178686", "title": "The acute thyroidal response to iodixed oil in severe endemic goiter.", "content": "The acute changes in serum thyrotropin (TSH) triiodothyronine (T3) and thyroxine (T4), were measured in 14 subjects, 4 to 10 (mean = 6) days following intramuscular iodized oil injection. In 8 subjects with small or absent goiter there was a significant fall in T3 and a rise in TSH concentrations, suggesting an acute inhibitory effect of the iodine. In 6 subjects with large multinodular goiters there was a marked rise in both T3 and T4, and reduction in the elevated basal TSH. Biochemical hyperthyroidism occurred in 3 of these subjects. The acute thyroid hormone response to iodized oil, whether inhibitory or stimulatory in a particular subject, depends both on goiter size and on the serum concentration of TSH.", "contents": "The acute thyroidal response to iodixed oil in severe endemic goiter. The acute changes in serum thyrotropin (TSH) triiodothyronine (T3) and thyroxine (T4), were measured in 14 subjects, 4 to 10 (mean = 6) days following intramuscular iodized oil injection. In 8 subjects with small or absent goiter there was a significant fall in T3 and a rise in TSH concentrations, suggesting an acute inhibitory effect of the iodine. In 6 subjects with large multinodular goiters there was a marked rise in both T3 and T4, and reduction in the elevated basal TSH. Biochemical hyperthyroidism occurred in 3 of these subjects. The acute thyroid hormone response to iodized oil, whether inhibitory or stimulatory in a particular subject, depends both on goiter size and on the serum concentration of TSH."} {"id": "PMID:178687", "title": "Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone, and prolactin in man.", "content": "Estrogen (E) reduces bioassayable GH-dependent serum somatomedin (SM) activity in acromegalics without affecting plasma growth hormone (GH) levels and inhibits the rise of SM activity normally produced by GH administration in GH-deficient subjects. We have now investigated the effect of E administration on serum SM activity and on plasma GH and prolactin (PRL) in 6 adult male subjects without pituitary pathology. Chronic E administration (ethinyl estradiol 0.5 mg/day for 7 to 70 days) reduced serum SM activity by 40 to 62% in each of 4 subjects (P less than 0.02 to less than 0.001). In 3 of the subjects, basal GH levels increased by 75 to 300% (P less than 0.05 to less than 0.001) and basal PRL levels increased by 90 to 200% (P less than 0.01 to less than 0.001). While iv administration of normal saline did not significantly affect either SM or GH, iv administration of E (bolus injection of 25 mg conjugated estrogens, USP) to 5 subjects resulted in: a) a 46 to 80% decrease in serum SM activity in all subjects, proceeding with an apparent half-life of 2 hours, becoming significant (P less than 0.05) at 2 hours (1 subject) to 3 hours (4 subjects), maximal at 6 hours, and persisting for 12 to 24 hours; b) GH elevation to 3 to 16 times baseline level (P less than 0.01) at 2 to 3 hours in 4 subjects; and c) no significant change of PRL levels in any subject. The mean GH response to iv E was maximal at a time (2 hours) when the mean SM activity had decreased only 20% and subsided well before the nadir of SM activity. The one patient without GH response to chronic or acute E administration may have been affected by absorption of triamcinolone being applied topically during the study. These results demonstrate that in males with normal pituitary function, E reduces serum SM activity, enhances basal GH and PRL secretion, and, upon iv injection, stimulates acute GH release. Although opposite chronic E effects upon GH and SM activity support a putative negative SM-GH feed-back mechanism, iv E administration apparently provokes acute GH release by a different mechanism. The half-life of serum SM activity in the human is probably much shorter than previously estimated.", "contents": "Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone, and prolactin in man. Estrogen (E) reduces bioassayable GH-dependent serum somatomedin (SM) activity in acromegalics without affecting plasma growth hormone (GH) levels and inhibits the rise of SM activity normally produced by GH administration in GH-deficient subjects. We have now investigated the effect of E administration on serum SM activity and on plasma GH and prolactin (PRL) in 6 adult male subjects without pituitary pathology. Chronic E administration (ethinyl estradiol 0.5 mg/day for 7 to 70 days) reduced serum SM activity by 40 to 62% in each of 4 subjects (P less than 0.02 to less than 0.001). In 3 of the subjects, basal GH levels increased by 75 to 300% (P less than 0.05 to less than 0.001) and basal PRL levels increased by 90 to 200% (P less than 0.01 to less than 0.001). While iv administration of normal saline did not significantly affect either SM or GH, iv administration of E (bolus injection of 25 mg conjugated estrogens, USP) to 5 subjects resulted in: a) a 46 to 80% decrease in serum SM activity in all subjects, proceeding with an apparent half-life of 2 hours, becoming significant (P less than 0.05) at 2 hours (1 subject) to 3 hours (4 subjects), maximal at 6 hours, and persisting for 12 to 24 hours; b) GH elevation to 3 to 16 times baseline level (P less than 0.01) at 2 to 3 hours in 4 subjects; and c) no significant change of PRL levels in any subject. The mean GH response to iv E was maximal at a time (2 hours) when the mean SM activity had decreased only 20% and subsided well before the nadir of SM activity. The one patient without GH response to chronic or acute E administration may have been affected by absorption of triamcinolone being applied topically during the study. These results demonstrate that in males with normal pituitary function, E reduces serum SM activity, enhances basal GH and PRL secretion, and, upon iv injection, stimulates acute GH release. Although opposite chronic E effects upon GH and SM activity support a putative negative SM-GH feed-back mechanism, iv E administration apparently provokes acute GH release by a different mechanism. The half-life of serum SM activity in the human is probably much shorter than previously estimated."} {"id": "PMID:178688", "title": "Use of biological characteristics to type Herpesvirus hominis types 1 and 2 in diagnostic laboratories.", "content": "Fifty clinical isolates of Herpesvirus hominis were typed by pock size on chicken embryo chorioallantoic membranes, sensitivity to heparin, and plaque formation on chicken embryo cell cultures. Of 19 isolates that were typed serologically, there was 100% concordance with respect to plaque formation. Pock size was incorrect in one instance and indeterminate in another. Heparin sensitivity was incorrect for one. Of 31 strains that were only biologically characterized, there were four for which heparin sensitivity did not agree with the other two characteristics. Of the three biological tests, the ability to form plaques in chick cell monolayer was the most reliable indicator type.", "contents": "Use of biological characteristics to type Herpesvirus hominis types 1 and 2 in diagnostic laboratories. Fifty clinical isolates of Herpesvirus hominis were typed by pock size on chicken embryo chorioallantoic membranes, sensitivity to heparin, and plaque formation on chicken embryo cell cultures. Of 19 isolates that were typed serologically, there was 100% concordance with respect to plaque formation. Pock size was incorrect in one instance and indeterminate in another. Heparin sensitivity was incorrect for one. Of 31 strains that were only biologically characterized, there were four for which heparin sensitivity did not agree with the other two characteristics. Of the three biological tests, the ability to form plaques in chick cell monolayer was the most reliable indicator type."} {"id": "PMID:178689", "title": "Diagnosis of herpes simplex virus infection by immunofluorescence.", "content": "The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections.", "contents": "Diagnosis of herpes simplex virus infection by immunofluorescence. The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections."} {"id": "PMID:178690", "title": "Immunoperoxidase technique for detection of antibodies to human cytomegalovirus.", "content": "The indirect immunoperoxidase antibody technique (IPA) has been applied to determine immunoglobulin (Ig)G to humans cytomegalovirus (CMV) antibodies in 114 blood donor sera, four cases of congenital cytomegalic inclusion disease, and four cases of acquired CMV infection. The results have been compared with those obtained with the CMV complement fixation (CF) test and indirect fluorescent antibody technique (IFA) for broad spectrum CMV antibody (sigmaAb) detection. IgG antibody has been detected by both CF and IPA. In healthy adult people IPA titers are usually higher than CF titers. In addition, IFA sigmaAb titers are generally higher than CF titers. Some sera negative by CF and IPA are positive at low dilutions by IFA sigmaAb antibody determination, due to the detection of small amounts of IgA or noncomplement-fixing IgG. Nonspecific results seem unlikely, since only nuclear inclusion fluorescence was interpreted as specific, as demonstrated by blocking tests. In acute CMV infection, the IFA sigmaAb and IPA IgG titers are essentially the same, except during the first weeks of infection, when IFA titers are higher and IgM is detectable. No cross-reactivity with other herpes group viruses, herpes simplex and varicella-zoster, was observed. Although some problems of nonspecific staining of cytoplasmic inclusions are shared by both methods, the IPA technique seems to possess the same degree of sensitivity and specificity as the IFA technique, but interpretation is easier and various procedural steps can be delayed without the technical problems associated with fluorescence microscopy.", "contents": "Immunoperoxidase technique for detection of antibodies to human cytomegalovirus. The indirect immunoperoxidase antibody technique (IPA) has been applied to determine immunoglobulin (Ig)G to humans cytomegalovirus (CMV) antibodies in 114 blood donor sera, four cases of congenital cytomegalic inclusion disease, and four cases of acquired CMV infection. The results have been compared with those obtained with the CMV complement fixation (CF) test and indirect fluorescent antibody technique (IFA) for broad spectrum CMV antibody (sigmaAb) detection. IgG antibody has been detected by both CF and IPA. In healthy adult people IPA titers are usually higher than CF titers. In addition, IFA sigmaAb titers are generally higher than CF titers. Some sera negative by CF and IPA are positive at low dilutions by IFA sigmaAb antibody determination, due to the detection of small amounts of IgA or noncomplement-fixing IgG. Nonspecific results seem unlikely, since only nuclear inclusion fluorescence was interpreted as specific, as demonstrated by blocking tests. In acute CMV infection, the IFA sigmaAb and IPA IgG titers are essentially the same, except during the first weeks of infection, when IFA titers are higher and IgM is detectable. No cross-reactivity with other herpes group viruses, herpes simplex and varicella-zoster, was observed. Although some problems of nonspecific staining of cytoplasmic inclusions are shared by both methods, the IPA technique seems to possess the same degree of sensitivity and specificity as the IFA technique, but interpretation is easier and various procedural steps can be delayed without the technical problems associated with fluorescence microscopy."} {"id": "PMID:178691", "title": "Detection of neonatal calf diarrhea virus, infant reovirus-like diarrhea virus, and a coronavirus using the fluorescent virus precipitin test.", "content": "Thirty-four calf and five infant fecal specimens were tested for the neonatal calf diarrhea virus (NCDV) and for the reovirus-like infantile diarrhea agent; respectively. The procedures used were the fluorescent virus precipitin test and immune electron microscopy. Fourteen of the calf stools contained detectable NCDV, and four of the five infant stools contained the reovirus-like human agent. Infectious NCDV was detected in four of the 34 calf fecal specimens when Madin-Darby bovine kidney cell cultures that had been inoculated with supernatant fluids from stool suspensions were stained with fluorescent antibody. The 20 calf stools that did not have detectable virus were examined for the bovine corona diarrhea virus. Coronavirus was found in two of these specimens.", "contents": "Detection of neonatal calf diarrhea virus, infant reovirus-like diarrhea virus, and a coronavirus using the fluorescent virus precipitin test. Thirty-four calf and five infant fecal specimens were tested for the neonatal calf diarrhea virus (NCDV) and for the reovirus-like infantile diarrhea agent; respectively. The procedures used were the fluorescent virus precipitin test and immune electron microscopy. Fourteen of the calf stools contained detectable NCDV, and four of the five infant stools contained the reovirus-like human agent. Infectious NCDV was detected in four of the 34 calf fecal specimens when Madin-Darby bovine kidney cell cultures that had been inoculated with supernatant fluids from stool suspensions were stained with fluorescent antibody. The 20 calf stools that did not have detectable virus were examined for the bovine corona diarrhea virus. Coronavirus was found in two of these specimens."} {"id": "PMID:178693", "title": "Control of cell division: a unifying hypothesis.", "content": "A constant feature of the initiation of cell division in a number of different cells is a rise in the intracellular level of calcium. The importance of cyclic nucleotides may depend on the way they interact with calcium. Cyclic AMP is apparently not an essential regulator of cell division but through its ability to modulate the intracellular level of calcium this cyclic nucleotide can exert profound effects on cell growth. In some systems (liver and salivary glands) cyclic AMP seems to augment the calcium signal whereas in others (lymphocytes and fibroblasts) it opposes calcium and can thus inhibit cell division. A rise in the level of calcium may be responsible for the parallel increase in cyclic GMP level which is usually associated with the stimulus to divide. An appealing feature of this calcium hypothesis is that it can account for the growth characteristics revealed by fibroblasts in tissue culture or embryonic cells during development. In both cases there is an initial phase of exponential growth during which I have proposed that the high level of calcium at mitosis persists into early G1 to provide the signal for the next division. In order to account for the sudden cessation of cell division at confluency, or at a specific stage during development, it is necessary to postulate that there is something different about the final mitosis which sets it apart from earlier mitoses. It is proposed that as the cells leave the last mitosis the level of calcium falls much more rapidly than it did during preceeding mitoses perhaps as a result of a more rapid rise in the level of cyclic AMP. This rapid rise in cyclic AMP level may have a dual function. Not only will it lower the level of calcium thus preventing further division, but it may also stimulate differentiation. Many of the embryonic cells which differentiate into specialized cells (lymphocytes, liver, salivary gland) retain the ability to divide if provided with appropriate stimuli. Although the nature of these stimuli vary considerably, they all seem to act by elevating the intracellular level of calcium.", "contents": "Control of cell division: a unifying hypothesis. A constant feature of the initiation of cell division in a number of different cells is a rise in the intracellular level of calcium. The importance of cyclic nucleotides may depend on the way they interact with calcium. Cyclic AMP is apparently not an essential regulator of cell division but through its ability to modulate the intracellular level of calcium this cyclic nucleotide can exert profound effects on cell growth. In some systems (liver and salivary glands) cyclic AMP seems to augment the calcium signal whereas in others (lymphocytes and fibroblasts) it opposes calcium and can thus inhibit cell division. A rise in the level of calcium may be responsible for the parallel increase in cyclic GMP level which is usually associated with the stimulus to divide. An appealing feature of this calcium hypothesis is that it can account for the growth characteristics revealed by fibroblasts in tissue culture or embryonic cells during development. In both cases there is an initial phase of exponential growth during which I have proposed that the high level of calcium at mitosis persists into early G1 to provide the signal for the next division. In order to account for the sudden cessation of cell division at confluency, or at a specific stage during development, it is necessary to postulate that there is something different about the final mitosis which sets it apart from earlier mitoses. It is proposed that as the cells leave the last mitosis the level of calcium falls much more rapidly than it did during preceeding mitoses perhaps as a result of a more rapid rise in the level of cyclic AMP. This rapid rise in cyclic AMP level may have a dual function. Not only will it lower the level of calcium thus preventing further division, but it may also stimulate differentiation. Many of the embryonic cells which differentiate into specialized cells (lymphocytes, liver, salivary gland) retain the ability to divide if provided with appropriate stimuli. Although the nature of these stimuli vary considerably, they all seem to act by elevating the intracellular level of calcium."} {"id": "PMID:178694", "title": "Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum.", "content": "The present study demonstrated the presence within the myocardium of phosphoprotein phosphatase activity which can account for dephosphorylation of a 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum that has been associated with the stimulatory effects of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase on calcium transport (Tada, M., Kirchberger, M. A., and Katz, A. M. (1975) J. Biol. Chem. 250:2640-2647). Dog cardiac microsomes, consisting mainly of fragmented sarcomplasmic reticulum, were phosphorylated by incubation with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, and subsequently washed with trichloroacetic acid or buffered KCl. Phosphorylated microsomes contained approximately 1 nmole of 32P bound per mg of microsomal protein, 32P labeling occurring almost exclusively at the 22,000 dalton component. Soluble phosphoprotein phosphatases, isolated from the cytosol, catalyzed dephosphorylation of 32P-labeled microsomes. The existence of a phosphoprotein phosphatase that is associated with the microsomes was demonstrated by the ability of the microsomes to dephosphorylate 32P-histone. This membrane-associated phosphatase activity can also account for a rapid decrease in the amount of 32P-labeling of the 22,000 dalton protein. The dephosphorylation of the phosphorylated 22,000 dalton protein by phosphoprotein phosphatase satisfies an important requirement for the phosphorylation of the 22,000 dalton protein to serve a physiological role, namely, its reversibility.", "contents": "Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum. The present study demonstrated the presence within the myocardium of phosphoprotein phosphatase activity which can account for dephosphorylation of a 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum that has been associated with the stimulatory effects of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase on calcium transport (Tada, M., Kirchberger, M. A., and Katz, A. M. (1975) J. Biol. Chem. 250:2640-2647). Dog cardiac microsomes, consisting mainly of fragmented sarcomplasmic reticulum, were phosphorylated by incubation with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, and subsequently washed with trichloroacetic acid or buffered KCl. Phosphorylated microsomes contained approximately 1 nmole of 32P bound per mg of microsomal protein, 32P labeling occurring almost exclusively at the 22,000 dalton component. Soluble phosphoprotein phosphatases, isolated from the cytosol, catalyzed dephosphorylation of 32P-labeled microsomes. The existence of a phosphoprotein phosphatase that is associated with the microsomes was demonstrated by the ability of the microsomes to dephosphorylate 32P-histone. This membrane-associated phosphatase activity can also account for a rapid decrease in the amount of 32P-labeling of the 22,000 dalton protein. The dephosphorylation of the phosphorylated 22,000 dalton protein by phosphoprotein phosphatase satisfies an important requirement for the phosphorylation of the 22,000 dalton protein to serve a physiological role, namely, its reversibility."} {"id": "PMID:178695", "title": "Oppositional effects of acetylcholine and isoproterenol on isometric tension and cyclic nucleotide concentrations in rabbit atria.", "content": "The effects of acetylcholine chloride and isoproterenol on myocardiial cyclic GMP, cyclic AMP and on isometric tension were studied in isolated electrically driven rabbit atria. Acetylcholine (0.5 muM) produced a significant decrease in isometric force that was associated with a significant elevation in atrial cyclic GMP. Cyclic AMP was significantly lowered at 15 seconds after the addition of acetylcholine, but was only slightly decreased at earlier time periods. Both the negative inotropic action and increase in cyclic GMP after addition of acetylcholine were blocked by atropine. Isoproterenol (0.1 muM) produced a significant increase in isometric tension that was associated with a significant elevation in atrial cyclic AMP levels, whereas cyclic GMP levels were not changed. These effects were blocked by practolol. The increases in atrial cyclic GMP and cyclic AMP following addition of acetylcholine and isoproterenol, respectively, preceded the changes in isometric tension in response to these agents. These data support the hypothesis that changes in intracellular levels of cyclic AMP and cyclic GMP may mediate the positive and negative inotropic effects of adrenergic and cholinergic agents.", "contents": "Oppositional effects of acetylcholine and isoproterenol on isometric tension and cyclic nucleotide concentrations in rabbit atria. The effects of acetylcholine chloride and isoproterenol on myocardiial cyclic GMP, cyclic AMP and on isometric tension were studied in isolated electrically driven rabbit atria. Acetylcholine (0.5 muM) produced a significant decrease in isometric force that was associated with a significant elevation in atrial cyclic GMP. Cyclic AMP was significantly lowered at 15 seconds after the addition of acetylcholine, but was only slightly decreased at earlier time periods. Both the negative inotropic action and increase in cyclic GMP after addition of acetylcholine were blocked by atropine. Isoproterenol (0.1 muM) produced a significant increase in isometric tension that was associated with a significant elevation in atrial cyclic AMP levels, whereas cyclic GMP levels were not changed. These effects were blocked by practolol. The increases in atrial cyclic GMP and cyclic AMP following addition of acetylcholine and isoproterenol, respectively, preceded the changes in isometric tension in response to these agents. These data support the hypothesis that changes in intracellular levels of cyclic AMP and cyclic GMP may mediate the positive and negative inotropic effects of adrenergic and cholinergic agents."} {"id": "PMID:178696", "title": "Influence on adipocyte plasma membrane bound protein kinase by feedback regulator.", "content": "Protein kinase, phosphodiesterase and adenylate cyclase of plasma membrane of adipocytes and the effect of the feedback regulator (FR) on these three enzymes was measured and compared. The basal level ratio of adenylate cyclase to phosphodiesterase to protein kinase was 1:1.9:3.0. Epinephrine and/or FR alters this ratio. FR stimulated protein kinase activity up to 3 fold in the presence of a wide range of enzyme concentrations, 5-50 mug membrane protein/tube. The concentration of FR effective for stimulation of membrane protein kinase was much greater than that needed for inhibition of adenylate cyclase and phosphodiesterases. The inhibition by FR on adenylate cyclase was the most potent effect among the 3 enzymes. 1 U (or 2 U/ml) of FR inhibited 50% of the adenylate cyclase activity in a defined system. The maximum effective concentration of FR for stimulation of membrane protein kinase was greater than 10 U/ml. Histone type 11A was the best substrate for protein phosphorylation so far observed. The FR stimulatory effect was observed at all substrate concentrations used ranging from 1-5 mg/ml. A NaF concentration curve shows that 15 mM NaF gave maximum phosphorylation. The stimulatory effect of FR was observed both in the presence and absence of NaF. Protein kinase of adipocyte plasma membrane was mainly cAMP-independent. The effect of FR (20 U/ml) in stimulation of protein phosphorylation was much greater than that of cAMP (1 X 10(-6) M). The cAMP and FR effects seemed to be additive. Preincubation of plasma membrane with FR in the absence of ATP resulted in no decrease but slight increase in protein kinase activity. A shift in protein kinase, phosphodiesterase and adenylate cyclase ratios by FR suggests the regulatory role of FR in cAMP metabolism in adipocytes.", "contents": "Influence on adipocyte plasma membrane bound protein kinase by feedback regulator. Protein kinase, phosphodiesterase and adenylate cyclase of plasma membrane of adipocytes and the effect of the feedback regulator (FR) on these three enzymes was measured and compared. The basal level ratio of adenylate cyclase to phosphodiesterase to protein kinase was 1:1.9:3.0. Epinephrine and/or FR alters this ratio. FR stimulated protein kinase activity up to 3 fold in the presence of a wide range of enzyme concentrations, 5-50 mug membrane protein/tube. The concentration of FR effective for stimulation of membrane protein kinase was much greater than that needed for inhibition of adenylate cyclase and phosphodiesterases. The inhibition by FR on adenylate cyclase was the most potent effect among the 3 enzymes. 1 U (or 2 U/ml) of FR inhibited 50% of the adenylate cyclase activity in a defined system. The maximum effective concentration of FR for stimulation of membrane protein kinase was greater than 10 U/ml. Histone type 11A was the best substrate for protein phosphorylation so far observed. The FR stimulatory effect was observed at all substrate concentrations used ranging from 1-5 mg/ml. A NaF concentration curve shows that 15 mM NaF gave maximum phosphorylation. The stimulatory effect of FR was observed both in the presence and absence of NaF. Protein kinase of adipocyte plasma membrane was mainly cAMP-independent. The effect of FR (20 U/ml) in stimulation of protein phosphorylation was much greater than that of cAMP (1 X 10(-6) M). The cAMP and FR effects seemed to be additive. Preincubation of plasma membrane with FR in the absence of ATP resulted in no decrease but slight increase in protein kinase activity. A shift in protein kinase, phosphodiesterase and adenylate cyclase ratios by FR suggests the regulatory role of FR in cAMP metabolism in adipocytes."} {"id": "PMID:178697", "title": "Insulin as an activator of cyclic AMP accumulation in rat fat cells.", "content": "In rat fat cells incubated with lipolytic agents and insulin for 30 or 60 minutes the increase in cyclic AMP accumulation due to norepinephrine and theophylline or adenosine deaminase added during the last 2-5 minutes of the incubation period was much greater as compared to cells incubated in the absence of insulin. Protaglandin E1 or nicotinic acid were just as anti-lipolytic as insulin but prior incubation with these agents markedly decreased the subsequent rise in cyclic AMP accumulation due to late catecholamine addition. The ability of insulin to increase cyclic AMP accumulation appeared to be secondary to inhibition of lipolysis. These results indicate that prostaglandin E1 and nicotinic acid are inhibitors of cyclic AMP accumulation while insulin acts by another mechanism to reduce lipolysis.", "contents": "Insulin as an activator of cyclic AMP accumulation in rat fat cells. In rat fat cells incubated with lipolytic agents and insulin for 30 or 60 minutes the increase in cyclic AMP accumulation due to norepinephrine and theophylline or adenosine deaminase added during the last 2-5 minutes of the incubation period was much greater as compared to cells incubated in the absence of insulin. Protaglandin E1 or nicotinic acid were just as anti-lipolytic as insulin but prior incubation with these agents markedly decreased the subsequent rise in cyclic AMP accumulation due to late catecholamine addition. The ability of insulin to increase cyclic AMP accumulation appeared to be secondary to inhibition of lipolysis. These results indicate that prostaglandin E1 and nicotinic acid are inhibitors of cyclic AMP accumulation while insulin acts by another mechanism to reduce lipolysis."} {"id": "PMID:178698", "title": "Parellel inhibition of LH-RH-induced cyclic AMP accumulation and LH and FSH release by LH-RH antagonists in vitro.", "content": "The relative potencies of seven antagonists of LH-RH to inhibit LH-RH-induced cyclic AMP accumulation and LH and FSH release were measured using rat hemipituitaries in vitro. At appropriate concentrations, [Des-His2, D-Ala6] LH-RH, [Des-His2, D-Ala6, des-Gly-NH210] LH-RH ethylamide, [Des-His2, D-Leu6] LH-RH, [D-Phe2] LH-RH, [Des-His2, Des-Gly-NH210] LH-RH propylamide, [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH led to parallel inhibition of cyclic AMP accumulation and LH and FSH release. [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH can inhibit 50% of LH-RH action at molar ratios of 100 and 30, respectively. These findings of parallel changes of cyclic AMP levels and LH and FSH release add strong support to the already obtained evidence for a mediator role of the adenylate cyclase system in the action of LH-RH in the anterior pituitary gland.", "contents": "Parellel inhibition of LH-RH-induced cyclic AMP accumulation and LH and FSH release by LH-RH antagonists in vitro. The relative potencies of seven antagonists of LH-RH to inhibit LH-RH-induced cyclic AMP accumulation and LH and FSH release were measured using rat hemipituitaries in vitro. At appropriate concentrations, [Des-His2, D-Ala6] LH-RH, [Des-His2, D-Ala6, des-Gly-NH210] LH-RH ethylamide, [Des-His2, D-Leu6] LH-RH, [D-Phe2] LH-RH, [Des-His2, Des-Gly-NH210] LH-RH propylamide, [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH led to parallel inhibition of cyclic AMP accumulation and LH and FSH release. [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH can inhibit 50% of LH-RH action at molar ratios of 100 and 30, respectively. These findings of parallel changes of cyclic AMP levels and LH and FSH release add strong support to the already obtained evidence for a mediator role of the adenylate cyclase system in the action of LH-RH in the anterior pituitary gland."} {"id": "PMID:178699", "title": "Effects of growth conditions on cyclic nucleotide phosphodiesterases of cultured fibroblasts.", "content": "Cyclic nucleotide phosphodiesterase activities of baby hamster kidney cells (BHK) grown in surface cultures were altered by modifying growth conditions. The untransformed BHK cells grown in medium containing 10% fetal calf serum showed non-linear LineweaverBurk plots for cyclic AMP phosphodiesterase activity with apparent Michaelis constants for cyclic AMP of approximately 5 and 30 muM. When these cells were placed in medium containing 1% fetal calf serum, linear kinetic plots for cyclic AMP phosphodiesterase with an apparent Km for cyclic AMP of approximately 20 muM were obtained. Modification of the apparent Km of BHK cell phosphodiesterase was detectable within 20 minutes after dillution of cells grown in 10% serum into fresh medium containing 1% serum. With the BHK cell line transformed with Rous sarcoma virus, differences in enzyme kinetics were not seen when these cells were diluted in 1% or 10% serum. In addition to the serum induced differences in the apparent Km of cyclic AMP phosphodiesterases of BHK cells, total cyclic AMP and cyclic GMP phosphodiesterase activities were also modified by growth conditions. BHK cells grown to high cell densities had three to five-fold higher total cyclic AMP activity than did the cells in less dense cultures. When the dense cell cultures were diluted into fresh medium containing 10% serum, total enzyme activities fell to levels comparable to those found in the rapidly growing cells at low cell densities. The reduction in total enzyme activity after dilution of BHK cells occurred rapidly and was influenced by cell density. A similar reduction of total enzyme activity was also seen in diluted RSV cells; however, the time course of the response differed from that seen in the untransformed cells.", "contents": "Effects of growth conditions on cyclic nucleotide phosphodiesterases of cultured fibroblasts. Cyclic nucleotide phosphodiesterase activities of baby hamster kidney cells (BHK) grown in surface cultures were altered by modifying growth conditions. The untransformed BHK cells grown in medium containing 10% fetal calf serum showed non-linear LineweaverBurk plots for cyclic AMP phosphodiesterase activity with apparent Michaelis constants for cyclic AMP of approximately 5 and 30 muM. When these cells were placed in medium containing 1% fetal calf serum, linear kinetic plots for cyclic AMP phosphodiesterase with an apparent Km for cyclic AMP of approximately 20 muM were obtained. Modification of the apparent Km of BHK cell phosphodiesterase was detectable within 20 minutes after dillution of cells grown in 10% serum into fresh medium containing 1% serum. With the BHK cell line transformed with Rous sarcoma virus, differences in enzyme kinetics were not seen when these cells were diluted in 1% or 10% serum. In addition to the serum induced differences in the apparent Km of cyclic AMP phosphodiesterases of BHK cells, total cyclic AMP and cyclic GMP phosphodiesterase activities were also modified by growth conditions. BHK cells grown to high cell densities had three to five-fold higher total cyclic AMP activity than did the cells in less dense cultures. When the dense cell cultures were diluted into fresh medium containing 10% serum, total enzyme activities fell to levels comparable to those found in the rapidly growing cells at low cell densities. The reduction in total enzyme activity after dilution of BHK cells occurred rapidly and was influenced by cell density. A similar reduction of total enzyme activity was also seen in diluted RSV cells; however, the time course of the response differed from that seen in the untransformed cells."} {"id": "PMID:178701", "title": "Cyclic AMP in human blood platelets: relation to platelet prostaglandin synthesis induced by centrifugation or surface contact.", "content": "Exposure of blood platelets to physical stimuli such as centrifugation, filtration through Sepharose gel, or stirring with particulate material leads to production of prostaglandins E2 and F2alpha and to a reduction in cAMP. These effects resemble those produced by ADP, epinephrine, collagen, and thrombin in association with the platelet release reaction but are less effectively inhibited by aspirin.", "contents": "Cyclic AMP in human blood platelets: relation to platelet prostaglandin synthesis induced by centrifugation or surface contact. Exposure of blood platelets to physical stimuli such as centrifugation, filtration through Sepharose gel, or stirring with particulate material leads to production of prostaglandins E2 and F2alpha and to a reduction in cAMP. These effects resemble those produced by ADP, epinephrine, collagen, and thrombin in association with the platelet release reaction but are less effectively inhibited by aspirin."} {"id": "PMID:178702", "title": "Multiple forms of glycogen synthase kinase: isolation of forms which are independent of cyclic AMP.", "content": "Rabbit renal cortex was found to contain three types of glycogen synthase kinase (GSK). Cylic AMP-dependent protein kinase (GSK-C) accounted for only a small fraction of the total GSK activity. The predominant type of GSK (GSK-P) could be adsorbed to phosphocellulose, but not to DEAE cellulose. The other major type (GSK-D) could be adsorbed to DEAE cellulose and exhibited several peaks when eluted with a linear NaC1 gradient. GSK-P and GSK-D were not affected by cyclic AMP or by the heat-stable protein inhibitor of cyclic AMP-dependent protein kinase. This suggests that cyclic AMP-independent mechanisms may play a major role in regulation of GSK. Neither GSK-P nor GSK-D were associated with the major peak of histone, kinase, casein kinase, protamine kinase or phosvitin kinase. Therefore it cannot be assumed that these protein kinase activities can be used to monitor GSK activity.", "contents": "Multiple forms of glycogen synthase kinase: isolation of forms which are independent of cyclic AMP. Rabbit renal cortex was found to contain three types of glycogen synthase kinase (GSK). Cylic AMP-dependent protein kinase (GSK-C) accounted for only a small fraction of the total GSK activity. The predominant type of GSK (GSK-P) could be adsorbed to phosphocellulose, but not to DEAE cellulose. The other major type (GSK-D) could be adsorbed to DEAE cellulose and exhibited several peaks when eluted with a linear NaC1 gradient. GSK-P and GSK-D were not affected by cyclic AMP or by the heat-stable protein inhibitor of cyclic AMP-dependent protein kinase. This suggests that cyclic AMP-independent mechanisms may play a major role in regulation of GSK. Neither GSK-P nor GSK-D were associated with the major peak of histone, kinase, casein kinase, protamine kinase or phosvitin kinase. Therefore it cannot be assumed that these protein kinase activities can be used to monitor GSK activity."} {"id": "PMID:178703", "title": "Effect of pregnancy and lactation on triglycerides of very-low-density lipoproteins of rat plasma.", "content": "Triglyceride in the blood of rats increased during pregnancy, decreased to control during lactation, and increased again on weaning. The triglyceride content of the very-low-density lipoproteins (d less than 1.006 g/ml) changed in parallel with that of the plasma, and its magnitude indicated that it was chiefly responsible for the transport of triglycerides in the blood. These changes were accompanied by changes in the electrophoretic pattern of the lipoproteins of rat plasma, but no such changes were observed in lipoproteins of ovine and caprine serum.", "contents": "Effect of pregnancy and lactation on triglycerides of very-low-density lipoproteins of rat plasma. Triglyceride in the blood of rats increased during pregnancy, decreased to control during lactation, and increased again on weaning. The triglyceride content of the very-low-density lipoproteins (d less than 1.006 g/ml) changed in parallel with that of the plasma, and its magnitude indicated that it was chiefly responsible for the transport of triglycerides in the blood. These changes were accompanied by changes in the electrophoretic pattern of the lipoproteins of rat plasma, but no such changes were observed in lipoproteins of ovine and caprine serum."} {"id": "PMID:178704", "title": "Effect of stress on blood leucocyte and milk somatic cell counts in dairy cows.", "content": "Blood and milk samples from Holstein cows were examined for total blood leucocyte count, differential blood leucocyte count, milk quality test, and somatic cell count in milk while the cows were stressed by corticotropin injection, confinement in a heat-humidity chamber, or environmental-heat stress by exposure during the hot summer months of June through November in southern Arizona. All three stressing conditions resulted in a moderate blood leucocytosis. Modest increases in somatic cell counts of milk were associated with corticotropin injection and environmental-heat stress. Positive correlations were recorded between blood leucocytes and somatic cell counts of milk in mastitis-free cows injected with corticotropin and between percent blood neutrophils and somatic cell counts of milk in environmental-heat stressed cows with no evidence of current mastitis.", "contents": "Effect of stress on blood leucocyte and milk somatic cell counts in dairy cows. Blood and milk samples from Holstein cows were examined for total blood leucocyte count, differential blood leucocyte count, milk quality test, and somatic cell count in milk while the cows were stressed by corticotropin injection, confinement in a heat-humidity chamber, or environmental-heat stress by exposure during the hot summer months of June through November in southern Arizona. All three stressing conditions resulted in a moderate blood leucocytosis. Modest increases in somatic cell counts of milk were associated with corticotropin injection and environmental-heat stress. Positive correlations were recorded between blood leucocytes and somatic cell counts of milk in mastitis-free cows injected with corticotropin and between percent blood neutrophils and somatic cell counts of milk in environmental-heat stressed cows with no evidence of current mastitis."} {"id": "PMID:178708", "title": "Age-related changes in the flight muscle mitochondria from the blowfly Sarcophaga bullata.", "content": "Flight muscle mitochondria have been isolated from female blowflies (Sarcophaga bullata) of different ages, alpha-Glycerophosphate and pyruvate-proline respiration rates increase during development. Only pyruvate-proline respiration declines toward senescence (30%). This decline can be overcome by ATP-NaHCO3. Cytochrome concentrations and hydrogen peroxide generation rates per protein increase during development but remain constant thereafter. Total NAD+ of metabolically completely oxidized mitochondria decreases during development; a small decline occurs between mature and senescent mitochondria. Respiring young mitochondria do not swell in potassium isethionate, very little in potassium chloride, and relatively slowly in potassium acetate. Mature and senescent mitochondria do swell in these three salts but cannot be differentiated from each other on this basis. None of the preparations swells in sodium chloride, sodium- or potassium Mops. While many differences exist between young and mature mitochondria, only the decline in pyruvate-proline respiration distinguishes mature from senescent mitochondria.", "contents": "Age-related changes in the flight muscle mitochondria from the blowfly Sarcophaga bullata. Flight muscle mitochondria have been isolated from female blowflies (Sarcophaga bullata) of different ages, alpha-Glycerophosphate and pyruvate-proline respiration rates increase during development. Only pyruvate-proline respiration declines toward senescence (30%). This decline can be overcome by ATP-NaHCO3. Cytochrome concentrations and hydrogen peroxide generation rates per protein increase during development but remain constant thereafter. Total NAD+ of metabolically completely oxidized mitochondria decreases during development; a small decline occurs between mature and senescent mitochondria. Respiring young mitochondria do not swell in potassium isethionate, very little in potassium chloride, and relatively slowly in potassium acetate. Mature and senescent mitochondria do swell in these three salts but cannot be differentiated from each other on this basis. None of the preparations swells in sodium chloride, sodium- or potassium Mops. While many differences exist between young and mature mitochondria, only the decline in pyruvate-proline respiration distinguishes mature from senescent mitochondria."} {"id": "PMID:178709", "title": "Nuclear inclusions: a study of aging in Drosophila.", "content": "Increased numbers and distribution of nuclear inclusions were correlated with aging in Drosophila imagoes. The various types of nuclear inclusions observed in the present study and those reported in the literature were categorized to their morphologies. It was noted that they may be located (a) in the nucleus proper, such as parallel fibrillar bundles, virus-like particles, tubulo-membraneous systems and amorphous fibrillo-granular deposits, (b) between the inner and outer nuclear membranes, such as cytoplasm-like intrusions, multilocular bodies and electron opaque vacuoles, and (c) outside the nucleus proper, such as those cytoplasmic invagination that interdigitate with infoldings of the nuclear membrane. A possible explanation of the relationship of these nuclear inclusions with aging and death is proposed.", "contents": "Nuclear inclusions: a study of aging in Drosophila. Increased numbers and distribution of nuclear inclusions were correlated with aging in Drosophila imagoes. The various types of nuclear inclusions observed in the present study and those reported in the literature were categorized to their morphologies. It was noted that they may be located (a) in the nucleus proper, such as parallel fibrillar bundles, virus-like particles, tubulo-membraneous systems and amorphous fibrillo-granular deposits, (b) between the inner and outer nuclear membranes, such as cytoplasm-like intrusions, multilocular bodies and electron opaque vacuoles, and (c) outside the nucleus proper, such as those cytoplasmic invagination that interdigitate with infoldings of the nuclear membrane. A possible explanation of the relationship of these nuclear inclusions with aging and death is proposed."} {"id": "PMID:178710", "title": "Fructose-1,6-bisphosphatase from young and adult rats.", "content": "Fructose-1,6-bisphosphatase (E.C. 3.1.3.11) was purified from the livers of young (69-86 days) and adult (370-386 days) Fisher rats. The enzyme preparations were examined for increasing amounts of missynthesized proteins by means of heat-inactivation as well as for differences in regulatory properties. No significant difference with respect to the fraction of rapidly heat-inactivated enzyme or Km- and Ki-values was found. These results do not support the hypothesis that error accumulation resulting in an error catastrophe is a general phenomenon underlying senescence and death.", "contents": "Fructose-1,6-bisphosphatase from young and adult rats. Fructose-1,6-bisphosphatase (E.C. 3.1.3.11) was purified from the livers of young (69-86 days) and adult (370-386 days) Fisher rats. The enzyme preparations were examined for increasing amounts of missynthesized proteins by means of heat-inactivation as well as for differences in regulatory properties. No significant difference with respect to the fraction of rapidly heat-inactivated enzyme or Km- and Ki-values was found. These results do not support the hypothesis that error accumulation resulting in an error catastrophe is a general phenomenon underlying senescence and death."} {"id": "PMID:178792", "title": "Endodermally-derived and neural crest-derived differentiation antigens expressed by a human lung tumor.", "content": "The plasma membrane antigens of an undifferentiated small cell (oat cell) carcinoma of the lung were studied by the indirect immunofluorescence method on frozen section substrates with a rabbit antiserum prepared to the tumor plasma membrane fraction. After appropriate absorption of the antiserum, at least two differentiation antigens present on the tumor cells but undetectable on normal lung surface or glandular epithelial cells were identified. One antigen(s) was characteristic of certain normal, endodermally-derived epithelial cells of the digestive system, including those of colonic mucosa, hepatic ducts, pancreatic ducts and acini, and islets of Langerhans. The other antigen(s) was characteristic of certain normal, neural crest-derived cells in the peripheral nervous system, including cells in peripheral nerve, dorsal root ganglion, and anterior roots of the spinal cord; parasympathetic ganglion cells in the colon; and small nerves and nerve processes in the lung, colon, and skin. It was concluded that the presence of these differentiation antigens on the tumor cells resulted from the expression of gene products repressed in the normal cell of origin of the tumor.", "contents": "Endodermally-derived and neural crest-derived differentiation antigens expressed by a human lung tumor. The plasma membrane antigens of an undifferentiated small cell (oat cell) carcinoma of the lung were studied by the indirect immunofluorescence method on frozen section substrates with a rabbit antiserum prepared to the tumor plasma membrane fraction. After appropriate absorption of the antiserum, at least two differentiation antigens present on the tumor cells but undetectable on normal lung surface or glandular epithelial cells were identified. One antigen(s) was characteristic of certain normal, endodermally-derived epithelial cells of the digestive system, including those of colonic mucosa, hepatic ducts, pancreatic ducts and acini, and islets of Langerhans. The other antigen(s) was characteristic of certain normal, neural crest-derived cells in the peripheral nervous system, including cells in peripheral nerve, dorsal root ganglion, and anterior roots of the spinal cord; parasympathetic ganglion cells in the colon; and small nerves and nerve processes in the lung, colon, and skin. It was concluded that the presence of these differentiation antigens on the tumor cells resulted from the expression of gene products repressed in the normal cell of origin of the tumor."} {"id": "PMID:178793", "title": "Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. I. Evidence for the existence of an intermediate, T.", "content": "The mechanism of the terminal steps in the lysis of antibody-sensitized tumor cells by complement (TAC) was studied. It was shown that once complement has reacted, lysis proceeded even in the absence of fluid-phase complement. Transformation of TAC to dead cells was found to be at least a two-step process: one of the steps was temperature dependent whereas the other was reversibly inhibited by EDTA. In analogy to the hemolytic system, TAC has been designated T.", "contents": "Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. I. Evidence for the existence of an intermediate, T. The mechanism of the terminal steps in the lysis of antibody-sensitized tumor cells by complement (TAC) was studied. It was shown that once complement has reacted, lysis proceeded even in the absence of fluid-phase complement. Transformation of TAC to dead cells was found to be at least a two-step process: one of the steps was temperature dependent whereas the other was reversibly inhibited by EDTA. In analogy to the hemolytic system, TAC has been designated T."} {"id": "PMID:178706", "title": "Four variables affecting magnitude of dentrifice abrasiveness.", "content": "A five-factor study was done on human dentin abrasion that involved two abrasives, either alone or in dentifrice form, two brush brands, two brush hardnesses, two concentrations, and two temperatures of testing. The hard brushes caused 3.6 times as much wear as the soft brushes, a greater influence than the abrasives compared. A brush X hardness interaction indicated that there is a wide variation among the stiffness gradings of toothbrushes. Tests run at 37 C were 28% less abrasive than those at room temperature, suggesting a softening of bristles because of the warmer temperature. A highly significant abrasive X concentration interaction showed that dentifrices became more than twice as abrasive on dilution form 100 to 50%, but that abrasives alone did not show such changes on dilution. The second study included two hardnesses, two abrasives, three diluents, four concentrations, and two replicates. An interaction was found between abrasive and diluent, showing that glycerine inhibited abrasion by 88% in comparison with saliva and CMC. A hardness X concentration interaction showed that wear varied widely with concentration for the hard brush but scarcely at all for the soft brush. These findings suggest that abrasiveness of dentifrices depends strongly on testing conditions and that no single set of conditions is suitable for evaluating dentifrice abrasiveness.", "contents": "Four variables affecting magnitude of dentrifice abrasiveness. A five-factor study was done on human dentin abrasion that involved two abrasives, either alone or in dentifrice form, two brush brands, two brush hardnesses, two concentrations, and two temperatures of testing. The hard brushes caused 3.6 times as much wear as the soft brushes, a greater influence than the abrasives compared. A brush X hardness interaction indicated that there is a wide variation among the stiffness gradings of toothbrushes. Tests run at 37 C were 28% less abrasive than those at room temperature, suggesting a softening of bristles because of the warmer temperature. A highly significant abrasive X concentration interaction showed that dentifrices became more than twice as abrasive on dilution form 100 to 50%, but that abrasives alone did not show such changes on dilution. The second study included two hardnesses, two abrasives, three diluents, four concentrations, and two replicates. An interaction was found between abrasive and diluent, showing that glycerine inhibited abrasion by 88% in comparison with saliva and CMC. A hardness X concentration interaction showed that wear varied widely with concentration for the hard brush but scarcely at all for the soft brush. These findings suggest that abrasiveness of dentifrices depends strongly on testing conditions and that no single set of conditions is suitable for evaluating dentifrice abrasiveness."} {"id": "PMID:178794", "title": "Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. II. Inhibition of transformation of T to dead cells by 3'5' cAMP.", "content": "Transformation of T to dead cells was prevented by 3'5' cAMP. The effect of 3'5' cAMP was dose, time, and temperature dependent. T washed free of 3'5' cAMP after short-term incubation proceeded to die to the same extent as control cells. After 3 hr of incubation of T with 3'5' cAMP the level of killing was significantly reduced. The 3'5' cyclic nucleotides of uridine, guanine, cytosine, and thymidine and the 2'3' cyclic adenosine nucleotide were not effective. It was concluded that prolonged treatment of T with 3'5' cAMP either irreversibly blocked the damage-producing process or facilitated the reapir of damaged sites.", "contents": "Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. II. Inhibition of transformation of T to dead cells by 3'5' cAMP. Transformation of T to dead cells was prevented by 3'5' cAMP. The effect of 3'5' cAMP was dose, time, and temperature dependent. T washed free of 3'5' cAMP after short-term incubation proceeded to die to the same extent as control cells. After 3 hr of incubation of T with 3'5' cAMP the level of killing was significantly reduced. The 3'5' cyclic nucleotides of uridine, guanine, cytosine, and thymidine and the 2'3' cyclic adenosine nucleotide were not effective. It was concluded that prolonged treatment of T with 3'5' cAMP either irreversibly blocked the damage-producing process or facilitated the reapir of damaged sites."} {"id": "PMID:178795", "title": "Naturally soluble tumor antigens from guinea pig hepatomas: isolation and partial characterization.", "content": "Naturally soluble tumor antigens were detected in the ascites fluid of guinea pigs bearing an ascites tumor and from exhausted tissue culture media of cultured tumor cells. Two antigenically distinct cell lines of diethylnitrosamine-induced strain-2 guinea pig hepatomas (line-10 and line-1) served as the source of tumor antigens. Tumor antigen activity was detected by four different techniques: immunodiffusion, inhibition of complement-mediated cytotoxicity, inhibition of membrane immunofluorescence, and delayed cutaneous hypersensitivity. With syngeneic tumor-specific antiserum, line-10 guinea pig tumor antigens were detected by immunofluorescence in the concentrated ascites and tissue culture fluids. With a xenogenic antiserum, demonstrated to be tumor specific, line-10 tumor antigens were detected not only in the concentrated ascites and tissue culture fluids but also in two of the partially purified fractions of these fluids. When the line-10 concentrated ascites and its fraction I were subjected to ultracentrifugation at 300,000 x G for 1 hr, the antigen activity was retained in the supernatant and thus by this criterion the tumor antigens detected in these samples are soluble. Immunodiffusion data indicate that more than one antigen is present in the line-10 system since three lines of precipitation were detected when line-10 concentrated ascites was reacted with the line-10 tumor-specific antiserum. In contrast to this, the line-10-concentrated tissue culture fluid displayed only one line of precipitation. Although tumor antigens could not be demonstrated in the other antigenically distinct tumor cell line, line-1, by immunodiffusion or inhibition of membrane immunofluorescence, inhibition of complement-mediated cytotoxicity was able to detect tumor antigens in the line-1 concentrated ascites and tissue culture fluids.", "contents": "Naturally soluble tumor antigens from guinea pig hepatomas: isolation and partial characterization. Naturally soluble tumor antigens were detected in the ascites fluid of guinea pigs bearing an ascites tumor and from exhausted tissue culture media of cultured tumor cells. Two antigenically distinct cell lines of diethylnitrosamine-induced strain-2 guinea pig hepatomas (line-10 and line-1) served as the source of tumor antigens. Tumor antigen activity was detected by four different techniques: immunodiffusion, inhibition of complement-mediated cytotoxicity, inhibition of membrane immunofluorescence, and delayed cutaneous hypersensitivity. With syngeneic tumor-specific antiserum, line-10 guinea pig tumor antigens were detected by immunofluorescence in the concentrated ascites and tissue culture fluids. With a xenogenic antiserum, demonstrated to be tumor specific, line-10 tumor antigens were detected not only in the concentrated ascites and tissue culture fluids but also in two of the partially purified fractions of these fluids. When the line-10 concentrated ascites and its fraction I were subjected to ultracentrifugation at 300,000 x G for 1 hr, the antigen activity was retained in the supernatant and thus by this criterion the tumor antigens detected in these samples are soluble. Immunodiffusion data indicate that more than one antigen is present in the line-10 system since three lines of precipitation were detected when line-10 concentrated ascites was reacted with the line-10 tumor-specific antiserum. In contrast to this, the line-10-concentrated tissue culture fluid displayed only one line of precipitation. Although tumor antigens could not be demonstrated in the other antigenically distinct tumor cell line, line-1, by immunodiffusion or inhibition of membrane immunofluorescence, inhibition of complement-mediated cytotoxicity was able to detect tumor antigens in the line-1 concentrated ascites and tissue culture fluids."} {"id": "PMID:178796", "title": "Regulatory serum lipoproteins: regulation of lymphocyte stimulation by a species of low density lipoprotein.", "content": "Low density lipoproteins (LDL) containing apolipoprotein B were separated from 15 fresh normal human serum pools by three independent isolation methods including sequential ultracentrifugal flotation, affinity chromatography, and polyanion precipitation. A discrete subpopulation of LDL (LDL-In) was isolated which possessed comparable inhibitory activity for PHA, PWM, and allogenic cell stimulated human lymphocytes in vitro at concentrations of 1 to 10 mug protein/1 x 10(5) lymphocytes/0.25 ml culture. LDL-In was characterized by a mean buoyant density of 1.055 g/ml in KBr, a m.w. of 2 to 3 x 10(6) daltons and a composition of 20 to 25% protein and 75 to 80% lipid with beta electrophoretic mobility. The biologic activity of LDL-In was non-cytotoxic, independent of mitogen concentration, and dependent upon the concentration of serum in the culture assay. The effect was temporally dependent requiring approximately 24 hr for induction of a stable suppressed state. Suppression was reversible with shorter periods of exposure to LDL-In. LDL-In did not inhibit lymphocytes at periods greater than 19 hr after stimulation, suggesting that LDL-In may influence metabolis events associated with the inductive phase of lymphocyte activation by lectins and allogeneic cells. LDL-In was clearly distinguishable from T lymphocyte E rosette inhibitory factor since it did not influence E rosette function of lymphocytes. The physicochemical and biologic properties of LDL-In clearly distinguish this reguloratory lipoprotein from previously described immunoregulatory factors.", "contents": "Regulatory serum lipoproteins: regulation of lymphocyte stimulation by a species of low density lipoprotein. Low density lipoproteins (LDL) containing apolipoprotein B were separated from 15 fresh normal human serum pools by three independent isolation methods including sequential ultracentrifugal flotation, affinity chromatography, and polyanion precipitation. A discrete subpopulation of LDL (LDL-In) was isolated which possessed comparable inhibitory activity for PHA, PWM, and allogenic cell stimulated human lymphocytes in vitro at concentrations of 1 to 10 mug protein/1 x 10(5) lymphocytes/0.25 ml culture. LDL-In was characterized by a mean buoyant density of 1.055 g/ml in KBr, a m.w. of 2 to 3 x 10(6) daltons and a composition of 20 to 25% protein and 75 to 80% lipid with beta electrophoretic mobility. The biologic activity of LDL-In was non-cytotoxic, independent of mitogen concentration, and dependent upon the concentration of serum in the culture assay. The effect was temporally dependent requiring approximately 24 hr for induction of a stable suppressed state. Suppression was reversible with shorter periods of exposure to LDL-In. LDL-In did not inhibit lymphocytes at periods greater than 19 hr after stimulation, suggesting that LDL-In may influence metabolis events associated with the inductive phase of lymphocyte activation by lectins and allogeneic cells. LDL-In was clearly distinguishable from T lymphocyte E rosette inhibitory factor since it did not influence E rosette function of lymphocytes. The physicochemical and biologic properties of LDL-In clearly distinguish this reguloratory lipoprotein from previously described immunoregulatory factors."} {"id": "PMID:178797", "title": "Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens.", "content": "Both in vitro and in vivo murine cytomegalovirus (MCMV) infection depressed the responses of lymphocytes to both B and T cell mitogens. The possibilities that macrophages or nonspecific T cell inhibition of B cells might account for the depressed responses were eliminated. In vitro data suggested that B cell responses are more susceptible to this depression than T cell responses. The possibility that the depression of T cell responses is not a direct effect of viral infection of lymphocytes is discussed. To investigate further the interaction between B and T lymphocytes and MCMV, mice with B and T cell deficiences were studied. A comparison of the susceptibility of athymic Nu/Nu mice and T cell competent Nu/+ littermates to MCMV showed that the LD50 for Nu/Nu mice is 10-fold lower than that for Nu/+ mice, but Nu/+ mice given an LD50 of virus died much sooner after infection than Nu/Nu mice given an LD50. Pathogenic mechanisms responsible for death may be different in these two groups of mice. Similarly the MCMV LD50 for B cell-deficient mice (treated with goat anti-mouse IgM serum) was 10-fold lower than the LD50 for mice treated with normal goat serum, but given an LD50 of virus, the latter died sooner after infection than the former. In contrast, there was little difference between the LD50 or time of death after MCMV infection of CBA x DBA F1 male mice (which are deficient in their response to thymic independent antigens) and their normal littermates, the CBA x DBA F1 female mice.", "contents": "Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens. Both in vitro and in vivo murine cytomegalovirus (MCMV) infection depressed the responses of lymphocytes to both B and T cell mitogens. The possibilities that macrophages or nonspecific T cell inhibition of B cells might account for the depressed responses were eliminated. In vitro data suggested that B cell responses are more susceptible to this depression than T cell responses. The possibility that the depression of T cell responses is not a direct effect of viral infection of lymphocytes is discussed. To investigate further the interaction between B and T lymphocytes and MCMV, mice with B and T cell deficiences were studied. A comparison of the susceptibility of athymic Nu/Nu mice and T cell competent Nu/+ littermates to MCMV showed that the LD50 for Nu/Nu mice is 10-fold lower than that for Nu/+ mice, but Nu/+ mice given an LD50 of virus died much sooner after infection than Nu/Nu mice given an LD50. Pathogenic mechanisms responsible for death may be different in these two groups of mice. Similarly the MCMV LD50 for B cell-deficient mice (treated with goat anti-mouse IgM serum) was 10-fold lower than the LD50 for mice treated with normal goat serum, but given an LD50 of virus, the latter died sooner after infection than the former. In contrast, there was little difference between the LD50 or time of death after MCMV infection of CBA x DBA F1 male mice (which are deficient in their response to thymic independent antigens) and their normal littermates, the CBA x DBA F1 female mice."} {"id": "PMID:178798", "title": "Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells.", "content": "Supernatants of adherent mouse peritoneal exudate cells or human mononuclear cells were used as the source of lymphocyte activation factor (LAF). LAF was found to potentiate the effect of mitogens such as PHA and Con A on DNA synthesis by mouse thymocytes. However, LAF also was capable of reducing vigorous thymosyte reactions to Con A. Thus, LAF usually enhanced the effect of PHA on DNA synthesis by BALB/c thymocytes to a relatively greater degree than that of Con A. This change in the ratio of Con A to PHA response of thymocytes suggests that LAF can serve as a regulator of thymocyte DNA synthesis. Moreover, in the presence of LAF, allogeneic thymocytes developed the ability to have bidirectional mixed thymocyte reactions. Exposure to LAF not only improved the ability of parental thymocytes to act as responder cells, but, in addition, led to increased stimulatory activity of F1 thymocytes, presumably by promoting the differentiation of stimulator cells. These indications that LAF affected differentiation were investigated further by studying its effect on the cAMP content of thymocytes. LAF stimulated significant immediate but transient elevations of intracellular cAMP and adenylate cyclase activity in thymocyte membranes. In contrast, the mitogens themselves failed to elevate or to influence the effect of LAF on the content of intracellular cAMP of thymocytes. Furthermore, the potentiating effect of LAF on mitogen-induced thymocyte DNA synthesis at times was enhanced by exogenous cGMP, carbachol, or imidazole. These findings suggest that LAF, through its stimulation of cAMP levels in thymocytes may in turn promote thymocytes to differentiate sufficiently to become competent to proliferative in response to mitogens.", "contents": "Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells. Supernatants of adherent mouse peritoneal exudate cells or human mononuclear cells were used as the source of lymphocyte activation factor (LAF). LAF was found to potentiate the effect of mitogens such as PHA and Con A on DNA synthesis by mouse thymocytes. However, LAF also was capable of reducing vigorous thymosyte reactions to Con A. Thus, LAF usually enhanced the effect of PHA on DNA synthesis by BALB/c thymocytes to a relatively greater degree than that of Con A. This change in the ratio of Con A to PHA response of thymocytes suggests that LAF can serve as a regulator of thymocyte DNA synthesis. Moreover, in the presence of LAF, allogeneic thymocytes developed the ability to have bidirectional mixed thymocyte reactions. Exposure to LAF not only improved the ability of parental thymocytes to act as responder cells, but, in addition, led to increased stimulatory activity of F1 thymocytes, presumably by promoting the differentiation of stimulator cells. These indications that LAF affected differentiation were investigated further by studying its effect on the cAMP content of thymocytes. LAF stimulated significant immediate but transient elevations of intracellular cAMP and adenylate cyclase activity in thymocyte membranes. In contrast, the mitogens themselves failed to elevate or to influence the effect of LAF on the content of intracellular cAMP of thymocytes. Furthermore, the potentiating effect of LAF on mitogen-induced thymocyte DNA synthesis at times was enhanced by exogenous cGMP, carbachol, or imidazole. These findings suggest that LAF, through its stimulation of cAMP levels in thymocytes may in turn promote thymocytes to differentiate sufficiently to become competent to proliferative in response to mitogens."} {"id": "PMID:178799", "title": "Studies on T cell clonal expansion. II. The in vitro differentiation of pre-killer and memory T cells.", "content": "Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37 degrees C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. \"Memory\" T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activity increased within 24 hr but showed no further increases when the culture period was extended. In contrast, 45-day-old immune cells showed increasing lytic activity throughout a 4-day exposure to antigen. Augmentation of lytic activity in both cell populations was independent of DNA synthesis through the first 24 hr of culture. Subsequent increases in the activity of 45-day cells was dependent upon cell proliferation. Both the antigen-independent augmentation of lytic activity which followed culturing of immune cells, and the antigen-induced differentiation of memory cells were reversibly inhibited by a series of drugs which raised lymphocyte cAMP levels.", "contents": "Studies on T cell clonal expansion. II. The in vitro differentiation of pre-killer and memory T cells. Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37 degrees C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. \"Memory\" T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activity increased within 24 hr but showed no further increases when the culture period was extended. In contrast, 45-day-old immune cells showed increasing lytic activity throughout a 4-day exposure to antigen. Augmentation of lytic activity in both cell populations was independent of DNA synthesis through the first 24 hr of culture. Subsequent increases in the activity of 45-day cells was dependent upon cell proliferation. Both the antigen-independent augmentation of lytic activity which followed culturing of immune cells, and the antigen-induced differentiation of memory cells were reversibly inhibited by a series of drugs which raised lymphocyte cAMP levels."} {"id": "PMID:178800", "title": "Heterologous sera: a target for in vitro cell-mediated cytotoxicity.", "content": "During the course of studies in inbred Strain 2 Guinea pigs on in vitro cell-mediated cytotoxicity to viral induced fibrosarcomas, it was observed that fetal calf serum in the medium in which the target cells were grown was responsible in some instances for much of the cytotoxicity observed. This fetal calf serum-specific cytotoxicity seemed mainly mediated by T cells and appeared to be independent on histocompatibility between target and killer cells.", "contents": "Heterologous sera: a target for in vitro cell-mediated cytotoxicity. During the course of studies in inbred Strain 2 Guinea pigs on in vitro cell-mediated cytotoxicity to viral induced fibrosarcomas, it was observed that fetal calf serum in the medium in which the target cells were grown was responsible in some instances for much of the cytotoxicity observed. This fetal calf serum-specific cytotoxicity seemed mainly mediated by T cells and appeared to be independent on histocompatibility between target and killer cells."} {"id": "PMID:178801", "title": "The development by cytomegalovirus-infected cells of binding affinity for normal human immunoglobulin.", "content": "After infection with human cytomegalovirus (CMV), cells develop an affinity for normal human immunoglobulin G (IgG). This was demonstrated using 125iodine-labeled purified IgG. It was further demonstrated that the immunoglobulin molecule binds to CMV-infected cells via its Fc portion, and competition for binding to infected cells occurred between purified preparations of human IgG and the Fc fragment of human IgG. Whole sera from individuals with or without a high titer of anti-CMV antibody were labeled with 125iodine and it was demonstrated that serum from individuals with no anti-CMV antibody had an affinity for CMV-infected cells which probably reflected binding of IgG via its Fc fragment. The possible significance of these results in immunologic studies of human CMV is considered.", "contents": "The development by cytomegalovirus-infected cells of binding affinity for normal human immunoglobulin. After infection with human cytomegalovirus (CMV), cells develop an affinity for normal human immunoglobulin G (IgG). This was demonstrated using 125iodine-labeled purified IgG. It was further demonstrated that the immunoglobulin molecule binds to CMV-infected cells via its Fc portion, and competition for binding to infected cells occurred between purified preparations of human IgG and the Fc fragment of human IgG. Whole sera from individuals with or without a high titer of anti-CMV antibody were labeled with 125iodine and it was demonstrated that serum from individuals with no anti-CMV antibody had an affinity for CMV-infected cells which probably reflected binding of IgG via its Fc fragment. The possible significance of these results in immunologic studies of human CMV is considered."} {"id": "PMID:178802", "title": "Human lymphocyte subpopulations: giant SRBC rosettes.", "content": "Human thymus-derived lymphocytes have the ability to form rosettes with sheep red blood cells (SRBC) in vitro. In the investigation of rosettes of peripheral blood lymphocytes of 10 normal subjects, the number of SRBC adhering to the lymphocyte in each of 100 rosettes was assessed. The percentage of rosettes with SRBC greater than or equal to 36 per rosette was only 1.2 +/- 0.5. These were defined as giant SRBC rosettes. Peripheral blood lymphocytes were stimulated in vitro by four mitogens: sodium periodate, neuraminidase plus galactose oxidase, pokeweed mitogen, and concanavalin A. The lymphocytes were then cultured at 37 degrees C. The giant rosette-forming lymphocytes became significantly increased 4 to 24 hr after stimulation, prior to the appearance of lymphoblasts or increased incorporation of tritiated thymidine. The giant rosettes were not caused by the hemagglutinating properties of pokeweed mitogen and concanavalin A that were adsorbed on the lymphocyte surfaces. This was shown by the fact that, on removal of the receptors by trypsinization, they were regenerated on culture in vitro in the absence of the mitogens. It was concluded that giant SRBC rosettes constituted a marker for some of the activated lymphocytes. Their appearance was independent of the increase in size of the cells or of DNA synthesis. These receptors were intrinsic to lymphocytes and not caused by mitogens adsorbed on their surfaces.", "contents": "Human lymphocyte subpopulations: giant SRBC rosettes. Human thymus-derived lymphocytes have the ability to form rosettes with sheep red blood cells (SRBC) in vitro. In the investigation of rosettes of peripheral blood lymphocytes of 10 normal subjects, the number of SRBC adhering to the lymphocyte in each of 100 rosettes was assessed. The percentage of rosettes with SRBC greater than or equal to 36 per rosette was only 1.2 +/- 0.5. These were defined as giant SRBC rosettes. Peripheral blood lymphocytes were stimulated in vitro by four mitogens: sodium periodate, neuraminidase plus galactose oxidase, pokeweed mitogen, and concanavalin A. The lymphocytes were then cultured at 37 degrees C. The giant rosette-forming lymphocytes became significantly increased 4 to 24 hr after stimulation, prior to the appearance of lymphoblasts or increased incorporation of tritiated thymidine. The giant rosettes were not caused by the hemagglutinating properties of pokeweed mitogen and concanavalin A that were adsorbed on the lymphocyte surfaces. This was shown by the fact that, on removal of the receptors by trypsinization, they were regenerated on culture in vitro in the absence of the mitogens. It was concluded that giant SRBC rosettes constituted a marker for some of the activated lymphocytes. Their appearance was independent of the increase in size of the cells or of DNA synthesis. These receptors were intrinsic to lymphocytes and not caused by mitogens adsorbed on their surfaces."} {"id": "PMID:178804", "title": "Factors regulating growth and pigmentation of melanoma cells.", "content": "Growth and melanization are intimately related in melanoma cells. MSH, by promoting elevated cyclic AMP levels, causes increases in melanization, cessation of growth, and gross morphologic changes in Cloudman S-91 melanoma cells. Growth inhibition results from high levels of cyclic AMP while growth stimulation occurs with lower levels. During melanization, oxidation products of tyrosine are generated which are toxic to the cells. Genetic studies have revealed that some of these processes are related through common biochemical pathways. This article reviews work of recent years on such regulatory mechanisms in melanoma.", "contents": "Factors regulating growth and pigmentation of melanoma cells. Growth and melanization are intimately related in melanoma cells. MSH, by promoting elevated cyclic AMP levels, causes increases in melanization, cessation of growth, and gross morphologic changes in Cloudman S-91 melanoma cells. Growth inhibition results from high levels of cyclic AMP while growth stimulation occurs with lower levels. During melanization, oxidation products of tyrosine are generated which are toxic to the cells. Genetic studies have revealed that some of these processes are related through common biochemical pathways. This article reviews work of recent years on such regulatory mechanisms in melanoma."} {"id": "PMID:178805", "title": "Localization of adenosine o',5'-monophosphate in mouse epidermis by immunofluorescence.", "content": "Adenosine 3',5'-monophosphate (cyclic AMP) has been localized in mouse epidermal cells using an immunofluorescent technique. Within 10 min following the intraperitoneal injection of isoproterenol or 30 hr following the topical application of croton oil in acetone, staining was clearly visible in the cytoplasm of the basal cells.", "contents": "Localization of adenosine o',5'-monophosphate in mouse epidermis by immunofluorescence. Adenosine 3',5'-monophosphate (cyclic AMP) has been localized in mouse epidermal cells using an immunofluorescent technique. Within 10 min following the intraperitoneal injection of isoproterenol or 30 hr following the topical application of croton oil in acetone, staining was clearly visible in the cytoplasm of the basal cells."} {"id": "PMID:178806", "title": "Effects of reserpine, epidermal growth factor, and cyclic nucleotide modulators on epidermal mitosis.", "content": "The mouse ear G2 mitosis assay was modified for the screening of potential antimitotic agents. An inhibitory adrenergic influence, which maintains mitotic rate at a normally low level, was removed by pretreatment of mice with reserpine. This depletes endogenous catecholamines, produces a state of enhanced mitotic activity, and makes the epidermal cells particularly sensitive to mitotic inhibition by agents which elevate the levels of cyclic AMP. Isoproterenol [IC 50 approximately 1 X 10(-9) M], prostaglandins, dibutyryl cyclic AMP [IC 50 approximately 2 X 10(-5) M], papaverine, theophylline and 5' AMP were inhibitory in the assay, whereas dibutyryl cyclic GMP and the cholinergic stimulator carbamylcholine either stimulated or had no effect on mitosis. Epidermal growth factor was employed as an alternate means of stimulating cell division. Skin fron newborn mice or rats pretreated with this substance had increased epidermal mitotic activity which was inhibited cyclic AMP elevators.", "contents": "Effects of reserpine, epidermal growth factor, and cyclic nucleotide modulators on epidermal mitosis. The mouse ear G2 mitosis assay was modified for the screening of potential antimitotic agents. An inhibitory adrenergic influence, which maintains mitotic rate at a normally low level, was removed by pretreatment of mice with reserpine. This depletes endogenous catecholamines, produces a state of enhanced mitotic activity, and makes the epidermal cells particularly sensitive to mitotic inhibition by agents which elevate the levels of cyclic AMP. Isoproterenol [IC 50 approximately 1 X 10(-9) M], prostaglandins, dibutyryl cyclic AMP [IC 50 approximately 2 X 10(-5) M], papaverine, theophylline and 5' AMP were inhibitory in the assay, whereas dibutyryl cyclic GMP and the cholinergic stimulator carbamylcholine either stimulated or had no effect on mitosis. Epidermal growth factor was employed as an alternate means of stimulating cell division. Skin fron newborn mice or rats pretreated with this substance had increased epidermal mitotic activity which was inhibited cyclic AMP elevators."} {"id": "PMID:178807", "title": "Adrenocortical hydroxylase deficiencies in acne vulgaris.", "content": "To investigate the possible occurrence of partial 11- or 21-hydroxylase deficiences in acne, an androgen-dependent disorder, 11 women with chronic nodulocystic acne were subjected to a 24-hr infusion of ACTH and their urine analyzed for tetrahydro S and pregnanetrio. The results obtained were compared to those found in 8 control women. Seven of the patients exhibited elevated excretion of either tetrahydro S or pregnanetriol, probably indicative of partial 11- or 21-hydroxylase deficiencies, respectively.", "contents": "Adrenocortical hydroxylase deficiencies in acne vulgaris. To investigate the possible occurrence of partial 11- or 21-hydroxylase deficiences in acne, an androgen-dependent disorder, 11 women with chronic nodulocystic acne were subjected to a 24-hr infusion of ACTH and their urine analyzed for tetrahydro S and pregnanetrio. The results obtained were compared to those found in 8 control women. Seven of the patients exhibited elevated excretion of either tetrahydro S or pregnanetriol, probably indicative of partial 11- or 21-hydroxylase deficiencies, respectively."} {"id": "PMID:178810", "title": "Urinary excretion of carnitine in man.", "content": "A convenient assay procedure for urinary carnitine is described. Urinary excretion of carnitine is determined in human subjects in various experimental states. Average excretions by this procedure were 59.3+/-3.3 mg. per day in men and 44.1+/-2.9 mg. per day in women. Carnitine excretion had a wide variation in women during the menstrual cycle and reached a maximum at the time of ovulation, but the excretion was relatively constant in men. Marked increases in carnitine excretion were observed in the states with increased lipolysis induced by fasting or ACTH injection. This finding suggests that lipid mobilization might be reflected in the excretion of carnitine in urine.", "contents": "Urinary excretion of carnitine in man. A convenient assay procedure for urinary carnitine is described. Urinary excretion of carnitine is determined in human subjects in various experimental states. Average excretions by this procedure were 59.3+/-3.3 mg. per day in men and 44.1+/-2.9 mg. per day in women. Carnitine excretion had a wide variation in women during the menstrual cycle and reached a maximum at the time of ovulation, but the excretion was relatively constant in men. Marked increases in carnitine excretion were observed in the states with increased lipolysis induced by fasting or ACTH injection. This finding suggests that lipid mobilization might be reflected in the excretion of carnitine in urine."} {"id": "PMID:178811", "title": "Varicella-zoster virus and facial palsy.", "content": "Two cases of Ramsey-Hunt Syndrome are reported, one of which presented features of the Guillain-Barr\u00e9 Syndrome. It is suggested that the varicella-zoster virus is an aetiological factor in the Guillain-Barr\u00e9 Syndrome.", "contents": "Varicella-zoster virus and facial palsy. Two cases of Ramsey-Hunt Syndrome are reported, one of which presented features of the Guillain-Barr\u00e9 Syndrome. It is suggested that the varicella-zoster virus is an aetiological factor in the Guillain-Barr\u00e9 Syndrome."} {"id": "PMID:178812", "title": "Peripheral facial palsy and herpes zoster infection.", "content": "A clinical and virological study of 133 consecutive cases of peripheral facial palsy has provided evidence for simultaneous infection with the varicella-zoster virus in 9 patients (6-8 per cent). Seven of these presented differing but typical manifestations of the Ramsay Hunt syndrome, and the diagnosis was therefore strongly suspected on the basis of the clinical findings alone. The remaining two patients had neither herpetiform rash nor involvement of the eighth cranial nerve, and had been diagnosed in the clinic as typical cases of Bell's palsy. In this series the incidence of zoster infection in apparent idiopathic facial palsy was 1-8 per cent.", "contents": "Peripheral facial palsy and herpes zoster infection. A clinical and virological study of 133 consecutive cases of peripheral facial palsy has provided evidence for simultaneous infection with the varicella-zoster virus in 9 patients (6-8 per cent). Seven of these presented differing but typical manifestations of the Ramsay Hunt syndrome, and the diagnosis was therefore strongly suspected on the basis of the clinical findings alone. The remaining two patients had neither herpetiform rash nor involvement of the eighth cranial nerve, and had been diagnosed in the clinic as typical cases of Bell's palsy. In this series the incidence of zoster infection in apparent idiopathic facial palsy was 1-8 per cent."} {"id": "PMID:178813", "title": "Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias.", "content": "Five glycosphingolipids (GSL), glucosylceramide, lactosylceramide, trihexosylceramide, globoside, and hematoside (GM3) were studied in serum from normal human subjects and patients with dyslipoproteinemia and found to be exclusively associated with the various classes of serum lipoproteins. Based on a unit weight of lipoprotein protein, the total amount of GSL in serum normal subjects was twice as high in very low density lipoprotein (VLDL) (d less than 1.006 g/ml) and low density lipoprotein (LDL) (d 1.019-1.063 g/ml) as in high density lipoproteins HDL2 (d 1.063-1.125 g/ml) or HDL3 (d 1.125-1.21 g/ml). In abetalipoproteinemia the levels of serum GSL were slightly reduced when compared to normal serum and were all found in the only existing lipoprotein, HDL; this contained 2-3 moles of GSL/ mole of lipoprotein as compared to 0.5 GSL/mole in normal HDL. In hypobetalipoproteinemia and Tangier disease, the serum glycosphingolipids were 10 to 30% reduced in concentration compared to the 75% reduction in other lipids, and were again found to be associated only with the serum lipoproteins. The relative proportions of GSL did not vary substantially in the normo- and hypolipidemic subjects studied. Only in patients with homozygous familial hypercholesterolemia was there a significant (3-4-fold) elevation of all of the five GSL species and this elevation of all of the five GSL species and this elevation correlated well with that of the circulating cholesterol and LDL. On a molar basis the LDL of these patients contained the same amount of GSL as normal subjects (5 moles GSL/mole protein). It is concluded that: (1) glycosphingolipids are associated only with the major lipoprotein classes in both normal and dyslipoproteinemic serum; (2) the relative proportions of the five glycosphingolipids are not significantly affected by dyslipoproteinemia; (3) only in severe hypolipoproteinemia do the remaining serum lipoproteins carry a complement of glycosphingolipids greater than normal. Although our results establish that glycosphingolipids are intimately associated with serum lipoproteins, the mode of association or the structural and functional significance of such an association remains undetermined.", "contents": "Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias. Five glycosphingolipids (GSL), glucosylceramide, lactosylceramide, trihexosylceramide, globoside, and hematoside (GM3) were studied in serum from normal human subjects and patients with dyslipoproteinemia and found to be exclusively associated with the various classes of serum lipoproteins. Based on a unit weight of lipoprotein protein, the total amount of GSL in serum normal subjects was twice as high in very low density lipoprotein (VLDL) (d less than 1.006 g/ml) and low density lipoprotein (LDL) (d 1.019-1.063 g/ml) as in high density lipoproteins HDL2 (d 1.063-1.125 g/ml) or HDL3 (d 1.125-1.21 g/ml). In abetalipoproteinemia the levels of serum GSL were slightly reduced when compared to normal serum and were all found in the only existing lipoprotein, HDL; this contained 2-3 moles of GSL/ mole of lipoprotein as compared to 0.5 GSL/mole in normal HDL. In hypobetalipoproteinemia and Tangier disease, the serum glycosphingolipids were 10 to 30% reduced in concentration compared to the 75% reduction in other lipids, and were again found to be associated only with the serum lipoproteins. The relative proportions of GSL did not vary substantially in the normo- and hypolipidemic subjects studied. Only in patients with homozygous familial hypercholesterolemia was there a significant (3-4-fold) elevation of all of the five GSL species and this elevation of all of the five GSL species and this elevation correlated well with that of the circulating cholesterol and LDL. On a molar basis the LDL of these patients contained the same amount of GSL as normal subjects (5 moles GSL/mole protein). It is concluded that: (1) glycosphingolipids are associated only with the major lipoprotein classes in both normal and dyslipoproteinemic serum; (2) the relative proportions of the five glycosphingolipids are not significantly affected by dyslipoproteinemia; (3) only in severe hypolipoproteinemia do the remaining serum lipoproteins carry a complement of glycosphingolipids greater than normal. Although our results establish that glycosphingolipids are intimately associated with serum lipoproteins, the mode of association or the structural and functional significance of such an association remains undetermined."} {"id": "PMID:178814", "title": "The effects of N-hexyl-O-glucosyl sphingosine on normal cultured human fibroblasts: a chemical model for Gaucher's disease.", "content": "Normal human skin fibroblasts were grown in the presence of N-hexyl-O-glucosyl sphingosine (HGS), an inhibitor of aryl glucosidase and glucocerebrosidase. Tests of the cells with aryl glycosides showed that beta-glucosidase activity in the cells was drastically reduced while other enzyme activities (alpha-glucosidase, beta-galactosidase, and N-acetyl-beta-hexosaminidase) were normal or elevated. Exposure of cells to HGS for 28 days resulted in increased values for cell weight per plate, glucocerebroside concentration, and galactosyl-galactosylglucosyl ceramide concentration. The concentrations of total lipid, cholesterol, and protein were unchanged, as was the fatty acid distribution within the glycolipids. Chemically, the inhibitor-treated cells exhibited a model form of Gaucher's disease. Although many membranous cytoplasmic inclusions were induced by HGS, they were unlike the characteristic inclusions seen in individuals with the genetic disorder. Skin fibroblasts from a Gaucher patient showed no abnormalities in composition or appearance.", "contents": "The effects of N-hexyl-O-glucosyl sphingosine on normal cultured human fibroblasts: a chemical model for Gaucher's disease. Normal human skin fibroblasts were grown in the presence of N-hexyl-O-glucosyl sphingosine (HGS), an inhibitor of aryl glucosidase and glucocerebrosidase. Tests of the cells with aryl glycosides showed that beta-glucosidase activity in the cells was drastically reduced while other enzyme activities (alpha-glucosidase, beta-galactosidase, and N-acetyl-beta-hexosaminidase) were normal or elevated. Exposure of cells to HGS for 28 days resulted in increased values for cell weight per plate, glucocerebroside concentration, and galactosyl-galactosylglucosyl ceramide concentration. The concentrations of total lipid, cholesterol, and protein were unchanged, as was the fatty acid distribution within the glycolipids. Chemically, the inhibitor-treated cells exhibited a model form of Gaucher's disease. Although many membranous cytoplasmic inclusions were induced by HGS, they were unlike the characteristic inclusions seen in individuals with the genetic disorder. Skin fibroblasts from a Gaucher patient showed no abnormalities in composition or appearance."} {"id": "PMID:178815", "title": "The effect of sex on the quantity and properties of the very low density lipoprotein secreted by the liver in vitro.", "content": "Livers from normally fed male and female rats were perfused in vitro with different amounts of oleate, and the production and properties of the very low density lipoprotein (VLDL) were studied. The mobility of the VLDL in the zonal ultracentrifuge was dependent on the uptake of free fatty acid and on the sex of the animal from which the liver was obtained. A higher proportion of the VLDL secreted by livers from females displayed a more rapid mobility in the zonal ultracentrifuge and, in addition, contained less phospholipid and cholesterol per mole triglyceride than the VLDL from the male, suggestive of larger size of the VLDL secreted by livers from the female rats. Such differences were diminished when the VLDL was compared at equal output of triglyceride but unequal uptake of free fatty acid. These data suggest that the properties of the VLDL are only secondarily modulated by sex, and primarily result from differences in the capacities of livers from either male or female rats to synthesize triglyceride for transport as VLDL. The quantity of triglyceride secreted, regardless of sex, may be an important determinant of both size and number of the VLDL particles. The incorporation of endogenous hepatic fatty acid into VLDL triglyceride was diminished in livers from both sexes by increased uptake of oleate. The greater output of VLDL triglyceride by livers from female animals was dependent on both exogenous and endogenous fatty acids when relatively small quantities of exogenous oleate were available for uptake by the liver. The proportion of palmitate and oleate in the phospholipid of the VLDL secreted by livers from male rats decreased and the content of arachidonate increased with increasing uptake of oleate; no differences were observed in the composition of the phospholipid fatty acids among the various experimental female groups, although these contained more stearate and less oleate and linoleate compared to the male groups. The change of fatty acid composition of the VLDL phospholipid may reflect inclusion of specific types of phospholipid in the VLDL structure for transport of triglyceride from the liver under particular conditions.", "contents": "The effect of sex on the quantity and properties of the very low density lipoprotein secreted by the liver in vitro. Livers from normally fed male and female rats were perfused in vitro with different amounts of oleate, and the production and properties of the very low density lipoprotein (VLDL) were studied. The mobility of the VLDL in the zonal ultracentrifuge was dependent on the uptake of free fatty acid and on the sex of the animal from which the liver was obtained. A higher proportion of the VLDL secreted by livers from females displayed a more rapid mobility in the zonal ultracentrifuge and, in addition, contained less phospholipid and cholesterol per mole triglyceride than the VLDL from the male, suggestive of larger size of the VLDL secreted by livers from the female rats. Such differences were diminished when the VLDL was compared at equal output of triglyceride but unequal uptake of free fatty acid. These data suggest that the properties of the VLDL are only secondarily modulated by sex, and primarily result from differences in the capacities of livers from either male or female rats to synthesize triglyceride for transport as VLDL. The quantity of triglyceride secreted, regardless of sex, may be an important determinant of both size and number of the VLDL particles. The incorporation of endogenous hepatic fatty acid into VLDL triglyceride was diminished in livers from both sexes by increased uptake of oleate. The greater output of VLDL triglyceride by livers from female animals was dependent on both exogenous and endogenous fatty acids when relatively small quantities of exogenous oleate were available for uptake by the liver. The proportion of palmitate and oleate in the phospholipid of the VLDL secreted by livers from male rats decreased and the content of arachidonate increased with increasing uptake of oleate; no differences were observed in the composition of the phospholipid fatty acids among the various experimental female groups, although these contained more stearate and less oleate and linoleate compared to the male groups. The change of fatty acid composition of the VLDL phospholipid may reflect inclusion of specific types of phospholipid in the VLDL structure for transport of triglyceride from the liver under particular conditions."} {"id": "PMID:178817", "title": "Effects of sub-total gastro-intestinal pancreatectomy of the rat foetus.", "content": "Sub-total pancreatectomy in utero was performed in 18-day-old rat foetuses. Pancreatectomized, sham-operated and control foetuses were collected 3 days later and body weight, glucose and insulin levels in blood, and glycogen content and glucose-6-phosphatase (G-6-Pase) activity of the liver were determined. Pancreatectomized foetuses showed only very small pancreatic remnants (less than or equal to 1 mg) and accordingly their insulin levels were much lower (four to five times) than those of sham-operated or control foetuses; their blood glucose levels were slightly increased and liver glycogen content and G-6-Pase activity were slightly reduced; their body weights were also reduced. These results are discussed in relation to other relevant data in the literature. They afford direct experimental evidence of the endogenous origin of insulin in the foetal blood. It is suggested that during the last days of intra-uterine life insulin merely completes the action of the glucocorticoids on glycogen storage in rat foetal liver and probably contributes to foetal body growth. Its relative ineffectiveness on the foetal blood glucose level is not explained. As pancreatectomized foetuses develop sub-normal liver G-6-Pase activity, glucagon is probably not responsible for the increase in this activity occurring during normal development before birth.", "contents": "Effects of sub-total gastro-intestinal pancreatectomy of the rat foetus. Sub-total pancreatectomy in utero was performed in 18-day-old rat foetuses. Pancreatectomized, sham-operated and control foetuses were collected 3 days later and body weight, glucose and insulin levels in blood, and glycogen content and glucose-6-phosphatase (G-6-Pase) activity of the liver were determined. Pancreatectomized foetuses showed only very small pancreatic remnants (less than or equal to 1 mg) and accordingly their insulin levels were much lower (four to five times) than those of sham-operated or control foetuses; their blood glucose levels were slightly increased and liver glycogen content and G-6-Pase activity were slightly reduced; their body weights were also reduced. These results are discussed in relation to other relevant data in the literature. They afford direct experimental evidence of the endogenous origin of insulin in the foetal blood. It is suggested that during the last days of intra-uterine life insulin merely completes the action of the glucocorticoids on glycogen storage in rat foetal liver and probably contributes to foetal body growth. Its relative ineffectiveness on the foetal blood glucose level is not explained. As pancreatectomized foetuses develop sub-normal liver G-6-Pase activity, glucagon is probably not responsible for the increase in this activity occurring during normal development before birth."} {"id": "PMID:178819", "title": "Ultrastructural observations of lethal yellow (Ay/Ay) mouse embryos.", "content": "Ay/Ay embroys were identified by the presence of large exluded blastomeres (Pedersen, 1974) and examined cytologically and ultrastructurally. Cell organelles, inclusions and junctions in the excluded blastomeres were compared with those of non-excluded cells of Ay/Ay embryos and control embryos. Excluded blastomeres always had the fine structural characteristics of earlier developmental stages and may have arrested at the 4- to 8-cell stage of slightly later. Interior cells (inner cell mass) were observed in all mutant blastocysts. Non-excluded cells of Ay/Ay embryos were normal until degenerative changes appear in the late blastocyst stage. The mode of action of the +Ay gene was not determined, but evidence from this study and others indicate that the effects of +Ay gene action occur over a wide range of time in early cleavage and implantation.", "contents": "Ultrastructural observations of lethal yellow (Ay/Ay) mouse embryos. Ay/Ay embroys were identified by the presence of large exluded blastomeres (Pedersen, 1974) and examined cytologically and ultrastructurally. Cell organelles, inclusions and junctions in the excluded blastomeres were compared with those of non-excluded cells of Ay/Ay embryos and control embryos. Excluded blastomeres always had the fine structural characteristics of earlier developmental stages and may have arrested at the 4- to 8-cell stage of slightly later. Interior cells (inner cell mass) were observed in all mutant blastocysts. Non-excluded cells of Ay/Ay embryos were normal until degenerative changes appear in the late blastocyst stage. The mode of action of the +Ay gene was not determined, but evidence from this study and others indicate that the effects of +Ay gene action occur over a wide range of time in early cleavage and implantation."} {"id": "PMID:178820", "title": "The pharmacology of an insect ganglion: actions of carbamylcholine and acetylcholine.", "content": "1. Methods for presenting dose-response data for the ganglionic actions of cholinergic agonists (e.g. carbamylcholine) are compared, using the mannitol-gap technique for electrophysiological recording of synaptic events at the cercal nerve, giant fibre synapse of the sixth abdominal ganglion of the cockroach Periplaneta americana. 2. At concentrations around 10(-5)M, carbamylcholine has no effect on ganglionic polarization but potentiates the monosynaptic EPSP. At 10(-4)M and higher concentrations, ganglionic depolarization is accompanied by a reduction of EPSP. 3. Pretreatment with eserine (10(-6) M) considerably shifts the dose-response curve for acetylcholine so that synaptic transmission is consistently sensitive to 10(-6) M acetylcholine.", "contents": "The pharmacology of an insect ganglion: actions of carbamylcholine and acetylcholine. 1. Methods for presenting dose-response data for the ganglionic actions of cholinergic agonists (e.g. carbamylcholine) are compared, using the mannitol-gap technique for electrophysiological recording of synaptic events at the cercal nerve, giant fibre synapse of the sixth abdominal ganglion of the cockroach Periplaneta americana. 2. At concentrations around 10(-5)M, carbamylcholine has no effect on ganglionic polarization but potentiates the monosynaptic EPSP. At 10(-4)M and higher concentrations, ganglionic depolarization is accompanied by a reduction of EPSP. 3. Pretreatment with eserine (10(-6) M) considerably shifts the dose-response curve for acetylcholine so that synaptic transmission is consistently sensitive to 10(-6) M acetylcholine."} {"id": "PMID:178821", "title": "The requirement for membrane sialic acid in the stimulation of superoxide production during phagocytosis by human polymorphonuclear leukocytes.", "content": "The effect of desialylation on phagocytosis of latex particles and oxidative metabolism of human polymorphonuclear leukocytes was studied. Removal of 20% total leukocyte sialic acid by bacterial neuraminidase had no effect on phagocytosis of latex particles and phagocytosis-associated activation of hexose monophosphate shunt in human polymorphonuclear leukocytes. In contrast, desialylation prevented the stimulation of superoxide production either by phagocytosis or by concanavalin A. It is concluded that membrane sialic acid is essential for the stimulation of superoxide production by human polymorphonuclear leukocytes.", "contents": "The requirement for membrane sialic acid in the stimulation of superoxide production during phagocytosis by human polymorphonuclear leukocytes. The effect of desialylation on phagocytosis of latex particles and oxidative metabolism of human polymorphonuclear leukocytes was studied. Removal of 20% total leukocyte sialic acid by bacterial neuraminidase had no effect on phagocytosis of latex particles and phagocytosis-associated activation of hexose monophosphate shunt in human polymorphonuclear leukocytes. In contrast, desialylation prevented the stimulation of superoxide production either by phagocytosis or by concanavalin A. It is concluded that membrane sialic acid is essential for the stimulation of superoxide production by human polymorphonuclear leukocytes."} {"id": "PMID:178822", "title": "A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus.", "content": "A quantitative Abelson murine leukemia virus (A-MuLV) lymphoid cell transformation assay has been developed using a semisolid agarose culture system. Under these conditions lymphoid cell transformation was shown to vary linearly with the dose of A-MuLV used. The susceptibility of bone marrow cells from different strains of mice to A-MuLV-induced transformation can be estimated using the agarose assay. Strains with bone marrow cells of high, medium, and low susceptibility to A-MuLV can be identified. The assay has been used to study the susceptibility of cells from lymphoid organs of fetal and adult mice to A-MuLV. Cell suspensions from fetal liver, adult bone marrow, and adult spleen are susceptible to A-MuLV, while thymocytes are resistant to A-MuLV-induced transformation. Bovine serum albumin gradient fractionation of bone marrow cells before infection with A-MuLV demonstrates that the majority of A-MuLV-sensitive cells are recovered in a broad band partially overlapping the majority of the nucleated cells. The agarose assay system allows study of A-MuLV-lymphoid cell interaction at the level of single cell-single virus particle interaction.", "contents": "A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. A quantitative Abelson murine leukemia virus (A-MuLV) lymphoid cell transformation assay has been developed using a semisolid agarose culture system. Under these conditions lymphoid cell transformation was shown to vary linearly with the dose of A-MuLV used. The susceptibility of bone marrow cells from different strains of mice to A-MuLV-induced transformation can be estimated using the agarose assay. Strains with bone marrow cells of high, medium, and low susceptibility to A-MuLV can be identified. The assay has been used to study the susceptibility of cells from lymphoid organs of fetal and adult mice to A-MuLV. Cell suspensions from fetal liver, adult bone marrow, and adult spleen are susceptible to A-MuLV, while thymocytes are resistant to A-MuLV-induced transformation. Bovine serum albumin gradient fractionation of bone marrow cells before infection with A-MuLV demonstrates that the majority of A-MuLV-sensitive cells are recovered in a broad band partially overlapping the majority of the nucleated cells. The agarose assay system allows study of A-MuLV-lymphoid cell interaction at the level of single cell-single virus particle interaction."} {"id": "PMID:178823", "title": "Association between mitogenicity and immunogenicity of 4-hydroxy-3,5-dinitrophenacetyl-lipopolysaccharide, a T-independent antigen.", "content": "Polymyxin B, which is a basic polypeptide produced by various strains of Bacillus Polymyxa, has previously been shown to prevent the lethal effect of LPS and to neutralize the Schwartzmann reaction. In this study we have investigated the interactions between polymyxin B and lipopolysaccharide (LPS) and hapten LPS conjugates. Polymyxin B was found to suppress mitogenicity of LPS and also to inhibit immunogenicity of the hapten conjugate 4-hydroxy-3,5-dinitrophenacetyl (NNP)-LPS. Inhibition was not due to interference with the expression of NNP determinants nor to cross-reactivity between PB and the hapten. Since mitogenicity and immunogenicity decreased in parallel, we conclude that B-cell activation in specific thymus independent responses does not take place in the absence of a nonspecific (non-Ig-mediated) signal.", "contents": "Association between mitogenicity and immunogenicity of 4-hydroxy-3,5-dinitrophenacetyl-lipopolysaccharide, a T-independent antigen. Polymyxin B, which is a basic polypeptide produced by various strains of Bacillus Polymyxa, has previously been shown to prevent the lethal effect of LPS and to neutralize the Schwartzmann reaction. In this study we have investigated the interactions between polymyxin B and lipopolysaccharide (LPS) and hapten LPS conjugates. Polymyxin B was found to suppress mitogenicity of LPS and also to inhibit immunogenicity of the hapten conjugate 4-hydroxy-3,5-dinitrophenacetyl (NNP)-LPS. Inhibition was not due to interference with the expression of NNP determinants nor to cross-reactivity between PB and the hapten. Since mitogenicity and immunogenicity decreased in parallel, we conclude that B-cell activation in specific thymus independent responses does not take place in the absence of a nonspecific (non-Ig-mediated) signal."} {"id": "PMID:178824", "title": "Generation of superoxide anion and chemiluminescence by human monocytes during phagocytosis and on contact with surface-bound immunoglobulin G.", "content": "Extent of O-2-release and chemiluminescence, attributed to singlet oxygen, has been compared in human monocytes and neutrophils during phagocytosis, stimulation by the surface-active agent phorbol myristate acetate, or contact with aggregated IgG in a model of immune complex disease. Monocytes generated O-2-and chemiluminescence with each of the three stimuli, although values were significantly less than those of neutrophils from the same individuals. Lymphocytes had no significant activity in either assay with any stimulus. Oxygen metabolites released from mononuclear phagocytes are highly reactive and could play a part in both the beneficial and detrimental aspects of chronic inflammation.", "contents": "Generation of superoxide anion and chemiluminescence by human monocytes during phagocytosis and on contact with surface-bound immunoglobulin G. Extent of O-2-release and chemiluminescence, attributed to singlet oxygen, has been compared in human monocytes and neutrophils during phagocytosis, stimulation by the surface-active agent phorbol myristate acetate, or contact with aggregated IgG in a model of immune complex disease. Monocytes generated O-2-and chemiluminescence with each of the three stimuli, although values were significantly less than those of neutrophils from the same individuals. Lymphocytes had no significant activity in either assay with any stimulus. Oxygen metabolites released from mononuclear phagocytes are highly reactive and could play a part in both the beneficial and detrimental aspects of chronic inflammation."} {"id": "PMID:178825", "title": "Effect of dithiothreitol on meiotic maturation of mouse oocytes in vitro: dependence of the effect on N6,O2'-dibutyryl Adenosine 3',5'-cyclic monophosphate.", "content": "The inhibitory effect of dithiothreitol on meiotic maturation of mouse oocytes in vitro is a function of the intracellular dibutyryl cyclic AMP concentration. Inhibition of nuclear (germinal vesicle) breakdown by dibutyryl cyclic AMP is reversed upon transfer of oocytes to plain culture medium, whereas, transfer to medium containing dithiothreitol results in continued inhibition. Dithiothreitol significantly enhances the effectiveness of dibutyryl cyclic AMP as an inhibitor of meiotic maturation. These results suggest that the reported effect of sulfhydryl reducing agents on membrane dissolution and reconstitution, in both meiotic and mitotic cells, may be attributed to their influence on intracelular levels of cyclic AMP.", "contents": "Effect of dithiothreitol on meiotic maturation of mouse oocytes in vitro: dependence of the effect on N6,O2'-dibutyryl Adenosine 3',5'-cyclic monophosphate. The inhibitory effect of dithiothreitol on meiotic maturation of mouse oocytes in vitro is a function of the intracellular dibutyryl cyclic AMP concentration. Inhibition of nuclear (germinal vesicle) breakdown by dibutyryl cyclic AMP is reversed upon transfer of oocytes to plain culture medium, whereas, transfer to medium containing dithiothreitol results in continued inhibition. Dithiothreitol significantly enhances the effectiveness of dibutyryl cyclic AMP as an inhibitor of meiotic maturation. These results suggest that the reported effect of sulfhydryl reducing agents on membrane dissolution and reconstitution, in both meiotic and mitotic cells, may be attributed to their influence on intracelular levels of cyclic AMP."} {"id": "PMID:178826", "title": "Beating intraocular hearts: light-controlled rate by autonomic innervation from host iris.", "content": "The sympathetic adrenergic ground plexus of the rat iris is able to innervate whole embryonic hearts transplanted to the anterior eye chamber. The transplants beat continuously from the time of transplantation and for at least five months, initially at 150-200 beats/min, and later approximately 250 beats/min. From seven days postoperatively onwards increased light to the eye produced deceleration while decreased light produced acceleration of the transplants. The rate changes coincided with changes in pupil diameter. Topical atropine reduced the light dependent rate variations of the transplants, especically the dramatic decrease in rate at white light. Waking stress caused a large rate increase. The \"waking-effect\" was strongly reduced by sympathetic decentralization and completely abolished by propranolol. The high rate seen in red light was decreased to the low rate of white light by decentralization. Isoprenaline restored red light rate levels in the decentralized transplant. The intraocular heart thus receives a dual functional autonomic input from the host iris and becomes a sensitive monitor of an autonomic nervous activity that can easily be varied at will in a physiological way by changing the light influx to the eye.", "contents": "Beating intraocular hearts: light-controlled rate by autonomic innervation from host iris. The sympathetic adrenergic ground plexus of the rat iris is able to innervate whole embryonic hearts transplanted to the anterior eye chamber. The transplants beat continuously from the time of transplantation and for at least five months, initially at 150-200 beats/min, and later approximately 250 beats/min. From seven days postoperatively onwards increased light to the eye produced deceleration while decreased light produced acceleration of the transplants. The rate changes coincided with changes in pupil diameter. Topical atropine reduced the light dependent rate variations of the transplants, especically the dramatic decrease in rate at white light. Waking stress caused a large rate increase. The \"waking-effect\" was strongly reduced by sympathetic decentralization and completely abolished by propranolol. The high rate seen in red light was decreased to the low rate of white light by decentralization. Isoprenaline restored red light rate levels in the decentralized transplant. The intraocular heart thus receives a dual functional autonomic input from the host iris and becomes a sensitive monitor of an autonomic nervous activity that can easily be varied at will in a physiological way by changing the light influx to the eye."} {"id": "PMID:178827", "title": "Biochemical studies of taste sensation. III. Preparation of a suspension of bovine taste bud cells and their labeling with a fluorescent probe.", "content": "A method to prepare suspensions of taste bud cells is described. Bovine circumvallate papillae, which contain most of the taste buds in this animal, are incubated in collagenase-containing medium and the epidermal sidewall tissue is then dissected from the inner gelatinous dermis. The sidewall tissue, which contains the taste buds, is gently homogenized by manual operation of an all-glass homogenizer with a loose-fitting pestle. The suspended material is separated on a discontinous Ficoll gradient (2%, 8%, 10%, 12% w/w). The material banding at the 8-2% interface is greatly enriched in spindle-shaped cells that are morphologically similar to taste bud cells as they appear in situ. These cells are not seen when the procedure is done with tissues devoid of taste buds, namely the upper surface of the circumvallate papilla or epithelium from the intermolar eminence. Fluorescence analysis indicates that the hydrophobic probe, 8-anilino-1-naphthalenesulfonate (ANS), binds to relatively nonpolar sites in the suspension. It is postulated that the probe is adsorbing onto the surface membrane of the cell. These preparations may be useful in studying specificity and transduction in taste sensation.", "contents": "Biochemical studies of taste sensation. III. Preparation of a suspension of bovine taste bud cells and their labeling with a fluorescent probe. A method to prepare suspensions of taste bud cells is described. Bovine circumvallate papillae, which contain most of the taste buds in this animal, are incubated in collagenase-containing medium and the epidermal sidewall tissue is then dissected from the inner gelatinous dermis. The sidewall tissue, which contains the taste buds, is gently homogenized by manual operation of an all-glass homogenizer with a loose-fitting pestle. The suspended material is separated on a discontinous Ficoll gradient (2%, 8%, 10%, 12% w/w). The material banding at the 8-2% interface is greatly enriched in spindle-shaped cells that are morphologically similar to taste bud cells as they appear in situ. These cells are not seen when the procedure is done with tissues devoid of taste buds, namely the upper surface of the circumvallate papilla or epithelium from the intermolar eminence. Fluorescence analysis indicates that the hydrophobic probe, 8-anilino-1-naphthalenesulfonate (ANS), binds to relatively nonpolar sites in the suspension. It is postulated that the probe is adsorbing onto the surface membrane of the cell. These preparations may be useful in studying specificity and transduction in taste sensation."} {"id": "PMID:178829", "title": "Antibodies to Epstein-Barr virus and cytomegalovirus in Guillain-Barre syndrome.", "content": "Twenty-three patients with Guillain-Barr\u00e9 syndrome (GBS) were investigated for serum antibody titres against Epstein-Barr virus capsid antigen (EBV-VCA), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV1). The geometric mean EBV-VCA titre was 45 in GBS, compared with 15-22 in healthy adults and 60 in sarcoidosis. Nine of the 15 GBS patients (60%) from whom multiple serum specimens were available, displayed a four-fold variation in antibody titre to EBV-VCA during the course of their disease. The geometric mean titres against CMV and HSV were also slightly higher in GBS compared with controls, but no titre variations were observed. Serial samples of both serum and cerebrospinal fluid (CSF) were available from 2 patients. Serum antibody titres against EBV were significantly higher in both during the initial phase of the disease. Serum antibody titres against CMV were also significantly elevated in 1 patient, but not until the second month after onset. The CSF antibody titres against EBV were higher in the beginning of the disease compared with the values during convalescence, but the titres observed were low. No measurable CSF antibody titres against CMV were found. The observation of varying serum antibody titres against EBV during the course of GBS can be interpreted as primary infections or as manifestations of reactivated latent virus infections. Further studies of the pathogenetic significance of this for the aetiology of the disease are warranted.", "contents": "Antibodies to Epstein-Barr virus and cytomegalovirus in Guillain-Barre syndrome. Twenty-three patients with Guillain-Barr\u00e9 syndrome (GBS) were investigated for serum antibody titres against Epstein-Barr virus capsid antigen (EBV-VCA), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV1). The geometric mean EBV-VCA titre was 45 in GBS, compared with 15-22 in healthy adults and 60 in sarcoidosis. Nine of the 15 GBS patients (60%) from whom multiple serum specimens were available, displayed a four-fold variation in antibody titre to EBV-VCA during the course of their disease. The geometric mean titres against CMV and HSV were also slightly higher in GBS compared with controls, but no titre variations were observed. Serial samples of both serum and cerebrospinal fluid (CSF) were available from 2 patients. Serum antibody titres against EBV were significantly higher in both during the initial phase of the disease. Serum antibody titres against CMV were also significantly elevated in 1 patient, but not until the second month after onset. The CSF antibody titres against EBV were higher in the beginning of the disease compared with the values during convalescence, but the titres observed were low. No measurable CSF antibody titres against CMV were found. The observation of varying serum antibody titres against EBV during the course of GBS can be interpreted as primary infections or as manifestations of reactivated latent virus infections. Further studies of the pathogenetic significance of this for the aetiology of the disease are warranted."} {"id": "PMID:178830", "title": "Herpes encephalitis. Rapid diagnosis and treatment with antiviral drugs.", "content": "The use of specific IgM antibodies and direct electron-microscopic examination of brain biopsies or vesicle fluid was tested as means of raped diagnosis in 6 cases of herpes simplex encephalitis seen consecutively in Montreal. In 2 of 3 biopsies herpes viruses were seen by negative staining of a cell extract within 1 hr. In the negative case, the biopsy was done almost 1 month after onset. In 2 additional cases herpes virus particles were found directly in the fluid of isolated vesicles. In the last 2 cases, who survived, the diagnosis of herpes encephalitis rested upon the demonstration of a greater than 4-fold rise in complement fixing herpes simplex virus antibodies in convalescent sera and upon the appearance late in the course of the encephalitis of specific antibodies in the cerebrospinal fluid. The early appearance of specific IgM antibodies contributed to the diagnosis in 4 of the 6 cases. Antiviral therapy was attempted in alternate cases (3 cases) but was not successful. Brain biopsy is rarely performed for diagnostic purposes but when prompt antiviral therapy is contemplated, the examination of the biopsy material for herpes virus particles by electron microscopy in negative staining and thin sections can rapidly and reliably confirm the diagnosis.", "contents": "Herpes encephalitis. Rapid diagnosis and treatment with antiviral drugs. The use of specific IgM antibodies and direct electron-microscopic examination of brain biopsies or vesicle fluid was tested as means of raped diagnosis in 6 cases of herpes simplex encephalitis seen consecutively in Montreal. In 2 of 3 biopsies herpes viruses were seen by negative staining of a cell extract within 1 hr. In the negative case, the biopsy was done almost 1 month after onset. In 2 additional cases herpes virus particles were found directly in the fluid of isolated vesicles. In the last 2 cases, who survived, the diagnosis of herpes encephalitis rested upon the demonstration of a greater than 4-fold rise in complement fixing herpes simplex virus antibodies in convalescent sera and upon the appearance late in the course of the encephalitis of specific antibodies in the cerebrospinal fluid. The early appearance of specific IgM antibodies contributed to the diagnosis in 4 of the 6 cases. Antiviral therapy was attempted in alternate cases (3 cases) but was not successful. Brain biopsy is rarely performed for diagnostic purposes but when prompt antiviral therapy is contemplated, the examination of the biopsy material for herpes virus particles by electron microscopy in negative staining and thin sections can rapidly and reliably confirm the diagnosis."} {"id": "PMID:178831", "title": "A comparison of the fine structure of motor end-plates in Duchenne dystrophy and in human neurogenic diseases.", "content": "With the aim of investigating the pathogenesis of Duchenne dystrophy, and in particular the role of denervation, the fine structural features of motor end-plates in the limb muscles of 13 patients with Duchenne dystrophy were compared with those in 26 controls and 50 patients suffering from known neurogenic diseases. The wide variation in control end-plates es emphasised. The sole plates in Duchenne dystrophy tended to retract from the end-plate, and shared only sprout formation, enclodure of terminals in Schwann cell cytoplasm and (in one instance) close packing of neurofilaments in the terminal with the changes in denervating end-plates. In these latter, withdrawal of terminals from the sole and various degenerative figures were the rule. It was concluded that there is no adequate morphological evidence in motor end-plates to support the concept of Duchenne dystrophy as a neurogenic disease.", "contents": "A comparison of the fine structure of motor end-plates in Duchenne dystrophy and in human neurogenic diseases. With the aim of investigating the pathogenesis of Duchenne dystrophy, and in particular the role of denervation, the fine structural features of motor end-plates in the limb muscles of 13 patients with Duchenne dystrophy were compared with those in 26 controls and 50 patients suffering from known neurogenic diseases. The wide variation in control end-plates es emphasised. The sole plates in Duchenne dystrophy tended to retract from the end-plate, and shared only sprout formation, enclodure of terminals in Schwann cell cytoplasm and (in one instance) close packing of neurofilaments in the terminal with the changes in denervating end-plates. In these latter, withdrawal of terminals from the sole and various degenerative figures were the rule. It was concluded that there is no adequate morphological evidence in motor end-plates to support the concept of Duchenne dystrophy as a neurogenic disease."} {"id": "PMID:178832", "title": "Peripheral nerve changes induced by methyl n-butyl ketone and potentiation by methyl ethyl ketone.", "content": "A study of the sequential morphological changes in the peripheral nerve induced by experimental inhalation exposure of methyl n-butyl ketone (MBK) revealed that the earliest change was an increase in the number of neurofilaments in the large myelinated nerve fibers. This change occurred prior to axonal swelling or myelin thinning. As the duration of exposure lengthened the number of neurofilaments gradually increased and ultimately produced axonal swelling with secondary thinning of the myelin sheath. This appears to be the pathogenesis of the \"giant axonal\" neuropathy. Another change observed early in this neuropathy was the presence of inpouchings of the myelin sheath, which also increased in number in parallel to the duration of exposure. A careful study of the sequential changes in the entire motor unit did not show a predilection for early morphological changes at the axon terminal. Abnormalities at the neuromuscular junction occurred only after a full spectrum of changes were seen in the main nerve trunk, nerve roots and intramuscular nerves. An important observation was the marked potentiation of peripheral neurotoxicity observed when animals were exposed to MBK in combination with methyl ethyl ketone (MEK) at a ratio of 1:5, MBK:MEK. The latter solvent showed no neurotoxic effect alone. This might help explain a recent outbreak of a polyneuropathy affecting many workers. One further observation was that the sural nerve of a patient with prolonged exposure to MBK showed changes similar to those induced experimentally.", "contents": "Peripheral nerve changes induced by methyl n-butyl ketone and potentiation by methyl ethyl ketone. A study of the sequential morphological changes in the peripheral nerve induced by experimental inhalation exposure of methyl n-butyl ketone (MBK) revealed that the earliest change was an increase in the number of neurofilaments in the large myelinated nerve fibers. This change occurred prior to axonal swelling or myelin thinning. As the duration of exposure lengthened the number of neurofilaments gradually increased and ultimately produced axonal swelling with secondary thinning of the myelin sheath. This appears to be the pathogenesis of the \"giant axonal\" neuropathy. Another change observed early in this neuropathy was the presence of inpouchings of the myelin sheath, which also increased in number in parallel to the duration of exposure. A careful study of the sequential changes in the entire motor unit did not show a predilection for early morphological changes at the axon terminal. Abnormalities at the neuromuscular junction occurred only after a full spectrum of changes were seen in the main nerve trunk, nerve roots and intramuscular nerves. An important observation was the marked potentiation of peripheral neurotoxicity observed when animals were exposed to MBK in combination with methyl ethyl ketone (MEK) at a ratio of 1:5, MBK:MEK. The latter solvent showed no neurotoxic effect alone. This might help explain a recent outbreak of a polyneuropathy affecting many workers. One further observation was that the sural nerve of a patient with prolonged exposure to MBK showed changes similar to those induced experimentally."} {"id": "PMID:178833", "title": "Experimental panencephalitis induced in suckling mice by parainfluenza type 1 (6/94) virus. I. Clinical and pathological features.", "content": "Intracerebral inoculation of two strains of suckling mice with 6/94 virus, a parainfluenza type 1 virus originally isolated from two patients with multiple sclerosis, produced clinical disease 1-2 weeks after inoculation. Of 528 animals inoculated, 33% died (26% of the ICR strain and 76% of the BALB/c strain) usually between two or three weeks after injection. Animals that recovered appeared to develop normally. Pathological changes were of two types. Initially, there was a necrotizing panencephalitis with virus-specific intracytoplasmic inclusions in choroid and ependymal epithelial cells and neurons. The second major lesion appeared about 6 weeks post inoculation and consisted of a noninflammatory spongiform degeneration of white matter that primarily involved the cerebral hemispheres; a diffuse vacuolar encephalapathy primarily affecting the brain stem; and a persistent minimal inflammation.", "contents": "Experimental panencephalitis induced in suckling mice by parainfluenza type 1 (6/94) virus. I. Clinical and pathological features. Intracerebral inoculation of two strains of suckling mice with 6/94 virus, a parainfluenza type 1 virus originally isolated from two patients with multiple sclerosis, produced clinical disease 1-2 weeks after inoculation. Of 528 animals inoculated, 33% died (26% of the ICR strain and 76% of the BALB/c strain) usually between two or three weeks after injection. Animals that recovered appeared to develop normally. Pathological changes were of two types. Initially, there was a necrotizing panencephalitis with virus-specific intracytoplasmic inclusions in choroid and ependymal epithelial cells and neurons. The second major lesion appeared about 6 weeks post inoculation and consisted of a noninflammatory spongiform degeneration of white matter that primarily involved the cerebral hemispheres; a diffuse vacuolar encephalapathy primarily affecting the brain stem; and a persistent minimal inflammation."} {"id": "PMID:178834", "title": "Experimental panencephalitis induced in suckling mice, by parainfluenza type 1 (6/94) virus, II. Virologic studies.", "content": "6/94 virus, a parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced a chronic panencephalitis when inoculated intracerebrally into suckling ICR mice. Immunofluorescent staining revealed 6/94 viral antigen in ependyma, meninges, choroid plexus, and perivascular parenchymal sites from day 3 to 128 days after infection. Hemadsorption-neutralizing antibody was first detected between 20-25 days after infection and remained at high titers for 7 months. Using embryonated chicken eggs, virus was recovered from mouse brains for only 8 days, but could be recovered from brains grown in vitro as explants for 37 days after infection. In cell lines established from explanted brain tissue, immunofluorescence was the most sensitive indicator of virus presence, although infectious virus was not produced. Fusion of these mouse brain cells with human (W138) indicator cells was the most effective means of rescuing 6/94 virus.", "contents": "Experimental panencephalitis induced in suckling mice, by parainfluenza type 1 (6/94) virus, II. Virologic studies. 6/94 virus, a parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced a chronic panencephalitis when inoculated intracerebrally into suckling ICR mice. Immunofluorescent staining revealed 6/94 viral antigen in ependyma, meninges, choroid plexus, and perivascular parenchymal sites from day 3 to 128 days after infection. Hemadsorption-neutralizing antibody was first detected between 20-25 days after infection and remained at high titers for 7 months. Using embryonated chicken eggs, virus was recovered from mouse brains for only 8 days, but could be recovered from brains grown in vitro as explants for 37 days after infection. In cell lines established from explanted brain tissue, immunofluorescence was the most sensitive indicator of virus presence, although infectious virus was not produced. Fusion of these mouse brain cells with human (W138) indicator cells was the most effective means of rescuing 6/94 virus."} {"id": "PMID:178835", "title": "Experimental panencephalitis induced in suckling mice by parainfluenza I (6/94) virus. III. Ultrastructural studies.", "content": "Intracerebral inoculation of newborn mice with Parainfluenza I (6/94) virus produces a chronic panencephalitis. Electron microscopic studies were carried out over 125 days of the infection. Productive infection of choroidal and ependymal epithelial cells was seen from postinoculation days 2nd to the 8th. Fusion of adjacent choroid and ependymal cells resulted in giant cell formation. Completed virions were seen adsorbed to circulating macrophages and these cells replicated intracytoplasmic nucleocapsids. Neuronal infection was evident on the 3rd postinoculation day, was widespread by the 6th day postinoculation and persisted to the 35th day postinoculation. Nucleocapsid alignment and budding from neuronal plasma membranes was never seen. An initially intense mononuclear cell infiltrate subsided by the 35th day but residual inflammation persisted throughout the study. Late in the course of the infection, vacuolation of the neuropil and a periventricular and deep cerebral spongiform change was seen which could not be directly associated with local viral replication. These ultrastructural findings are correlated with prior light microscopic, virological and immunofluorescent studies of the infection and compared to other experimental models of myxovirus central nervous system infections.", "contents": "Experimental panencephalitis induced in suckling mice by parainfluenza I (6/94) virus. III. Ultrastructural studies. Intracerebral inoculation of newborn mice with Parainfluenza I (6/94) virus produces a chronic panencephalitis. Electron microscopic studies were carried out over 125 days of the infection. Productive infection of choroidal and ependymal epithelial cells was seen from postinoculation days 2nd to the 8th. Fusion of adjacent choroid and ependymal cells resulted in giant cell formation. Completed virions were seen adsorbed to circulating macrophages and these cells replicated intracytoplasmic nucleocapsids. Neuronal infection was evident on the 3rd postinoculation day, was widespread by the 6th day postinoculation and persisted to the 35th day postinoculation. Nucleocapsid alignment and budding from neuronal plasma membranes was never seen. An initially intense mononuclear cell infiltrate subsided by the 35th day but residual inflammation persisted throughout the study. Late in the course of the infection, vacuolation of the neuropil and a periventricular and deep cerebral spongiform change was seen which could not be directly associated with local viral replication. These ultrastructural findings are correlated with prior light microscopic, virological and immunofluorescent studies of the infection and compared to other experimental models of myxovirus central nervous system infections."} {"id": "PMID:178836", "title": "\"Paramyxovirus-like\" intranuclear inclusions occurring in the nervous system in diverse unrelated conditions.", "content": "Filamentous intranuclear inclusions similar to the \"paramyxovirus-like\" intranuclear inclusions described in active multiple sclerosis (MS) were observed incidentally in four patients who had diverse disorders such as rabies, mannosidosis, metachromatic leukodystrophy, cerebral aneurysm and ischemic infarcts. The observation is in support of the mounting evidence that the \"virus-like\" intranuclear inclusions are not specific for MS and may occur frequently in a variety of diverse conditions. Moreover, neither virological nor immunological evidence as to the viral nature of the intranuclear inclusions has been presented to date, and the intranuclear inclusions have been observed mostly in degenerating or autolyzed cells in biopsied or autopsied tissue samples. In view of all the circumstantial evidence, it is suggested that the intranuclear \"paramyxovirus-like\" inclusions may represent an alternation of nuclear chromatin common to antemortem degeneration and postmortem autolysis in a variety of cells, the nature of which remains to be elucidated.", "contents": "\"Paramyxovirus-like\" intranuclear inclusions occurring in the nervous system in diverse unrelated conditions. Filamentous intranuclear inclusions similar to the \"paramyxovirus-like\" intranuclear inclusions described in active multiple sclerosis (MS) were observed incidentally in four patients who had diverse disorders such as rabies, mannosidosis, metachromatic leukodystrophy, cerebral aneurysm and ischemic infarcts. The observation is in support of the mounting evidence that the \"virus-like\" intranuclear inclusions are not specific for MS and may occur frequently in a variety of diverse conditions. Moreover, neither virological nor immunological evidence as to the viral nature of the intranuclear inclusions has been presented to date, and the intranuclear inclusions have been observed mostly in degenerating or autolyzed cells in biopsied or autopsied tissue samples. In view of all the circumstantial evidence, it is suggested that the intranuclear \"paramyxovirus-like\" inclusions may represent an alternation of nuclear chromatin common to antemortem degeneration and postmortem autolysis in a variety of cells, the nature of which remains to be elucidated."} {"id": "PMID:178837", "title": "Organization of crustacean neuropil. II. Distribution of synaptic contacts on identified motor neurons in lobster stomatogastric ganglion.", "content": "Identified neurons in the stomatogastric ganglion of the lobster were examined and reconstructed by serial section electron microscopy. Each motor neuron consists of a soma, a primary process leading directly from the soma to the motor axon which leaves the ganglion, and a group of secondary processes which branch from the primary process and ramify within the neuropil. Synapses are found only on small processes in the synaptic neuropil, never on the primary processes or on larger secondary processes in the coarse neuropil. Nearly every secondary process of every neuron examined makes both pre- and postsynaptic contacts. Hence these neurons are not polarized into distinct pre- and postsynaptic regions but have both input and output distributed over each of the secondary processes in the neuropil. The conncetion between a specific pair of neurons is also distributed over several branches of both the pre- and the postsynaptic neurons. The restriction of synapses to the more distal portions of the secondary processes suggests that no single contact or localized group of contacts can exert an overrriding influence on the neuron by virtue of an especially advantageous position. The close proximity of input and output on most secondary processes suggests that synaptic input may be capable of directly influencing output without the intervention of action potentials. The distribution of specific synapses over several branches of both pre- and postsynaptic neurons suggests that each neuron functions as a whole without differentiation into specialized branches.", "contents": "Organization of crustacean neuropil. II. Distribution of synaptic contacts on identified motor neurons in lobster stomatogastric ganglion. Identified neurons in the stomatogastric ganglion of the lobster were examined and reconstructed by serial section electron microscopy. Each motor neuron consists of a soma, a primary process leading directly from the soma to the motor axon which leaves the ganglion, and a group of secondary processes which branch from the primary process and ramify within the neuropil. Synapses are found only on small processes in the synaptic neuropil, never on the primary processes or on larger secondary processes in the coarse neuropil. Nearly every secondary process of every neuron examined makes both pre- and postsynaptic contacts. Hence these neurons are not polarized into distinct pre- and postsynaptic regions but have both input and output distributed over each of the secondary processes in the neuropil. The conncetion between a specific pair of neurons is also distributed over several branches of both the pre- and the postsynaptic neurons. The restriction of synapses to the more distal portions of the secondary processes suggests that no single contact or localized group of contacts can exert an overrriding influence on the neuron by virtue of an especially advantageous position. The close proximity of input and output on most secondary processes suggests that synaptic input may be capable of directly influencing output without the intervention of action potentials. The distribution of specific synapses over several branches of both pre- and postsynaptic neurons suggests that each neuron functions as a whole without differentiation into specialized branches."} {"id": "PMID:178838", "title": "Evaluation of mithramycin in the treatment of anaplastic gliomas.", "content": "A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 mug/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.", "contents": "Evaluation of mithramycin in the treatment of anaplastic gliomas. A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 mug/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision."} {"id": "PMID:178840", "title": "Unusual bone-scan findings in acute osteomyelitis: case report.", "content": "In osteomyelitis, bone-scan findings precede the appearance of bone changes on radiographs. In cases where focal ischemia occurs, the earliest scan finding may be a \"cold\" area that later becomes \"hot\" as active periostitis develops.", "contents": "Unusual bone-scan findings in acute osteomyelitis: case report. In osteomyelitis, bone-scan findings precede the appearance of bone changes on radiographs. In cases where focal ischemia occurs, the earliest scan finding may be a \"cold\" area that later becomes \"hot\" as active periostitis develops."} {"id": "PMID:178841", "title": "Gallium-67 uptake by a malignant fibrous histiocytoma: case report.", "content": "Avid 67Ga-citrate uptake was observed in a malignant fibrous histiocytoma of the mediastinum. The realtionships of the tumor to the heart and liver was shown by 99mTc-sulfur colloid liver-spleen scanning and 99mTc-pertechnetate angiography performed in conjunction with a 67Ga-citrate whole-body scan. This is the first report of 67Ga-citrate uptake by this unusual tumor.", "contents": "Gallium-67 uptake by a malignant fibrous histiocytoma: case report. Avid 67Ga-citrate uptake was observed in a malignant fibrous histiocytoma of the mediastinum. The realtionships of the tumor to the heart and liver was shown by 99mTc-sulfur colloid liver-spleen scanning and 99mTc-pertechnetate angiography performed in conjunction with a 67Ga-citrate whole-body scan. This is the first report of 67Ga-citrate uptake by this unusual tumor."} {"id": "PMID:178842", "title": "Mechanism of localization of 99mTc-labeled pyrophosphate and tetracycline in infarcted myocardium.", "content": "The gross and subcellular localizations of 99mTc-labeled pyrophosphate and tetracycline in myocardial infarcts were studied in a rabbit model. Experiments utilizing double-nuclide labeling were carried out using a useful mapping technique. Concentration of the various chelates decreases in an expected manner from the center of the infarcted area toward its periphery, but it is higher near the epicardial surface than toward the endocardium. Technetium-99m-pyrophosphate is concentrated in the same infarcted areas as 45Ca ion or 32P-pyrophosphate, but to a much greater degree. The uptake is dependent on both the degree of necrosis and residual blood flow. Gel filtration experiments with rabbit serum indicate that 99mTc-tagged pyrophosphate, tetracycline, and diphosphonate are mainly protein-bound, whereas 32P-pyrophosphate is not. Subcellular localization studies show that 99mTc-tetracycline and 99mTc-pyrophosphate are bound primarily to soluble protein, and only a small fraction is associated with nuclei, mitochondria, and microsomes. The uptake of technetium chelates in myocardial infarcts may be due to the formation of polynuclear complexes with denatured macromolecules rather than to the deposition of calcium in mitochrondria.", "contents": "Mechanism of localization of 99mTc-labeled pyrophosphate and tetracycline in infarcted myocardium. The gross and subcellular localizations of 99mTc-labeled pyrophosphate and tetracycline in myocardial infarcts were studied in a rabbit model. Experiments utilizing double-nuclide labeling were carried out using a useful mapping technique. Concentration of the various chelates decreases in an expected manner from the center of the infarcted area toward its periphery, but it is higher near the epicardial surface than toward the endocardium. Technetium-99m-pyrophosphate is concentrated in the same infarcted areas as 45Ca ion or 32P-pyrophosphate, but to a much greater degree. The uptake is dependent on both the degree of necrosis and residual blood flow. Gel filtration experiments with rabbit serum indicate that 99mTc-tagged pyrophosphate, tetracycline, and diphosphonate are mainly protein-bound, whereas 32P-pyrophosphate is not. Subcellular localization studies show that 99mTc-tetracycline and 99mTc-pyrophosphate are bound primarily to soluble protein, and only a small fraction is associated with nuclei, mitochondria, and microsomes. The uptake of technetium chelates in myocardial infarcts may be due to the formation of polynuclear complexes with denatured macromolecules rather than to the deposition of calcium in mitochrondria."} {"id": "PMID:178843", "title": "Biological activity of 24,25-dihydroxycholecalciferol in chicks and rats.", "content": "The ability of 24R, 25- and 24S, 25-dihydroxycholecalciferol to stimulate intestinal calcium transport and bone calcium mobilization in chicks was measured. Enhancement of intestinal calcium transport by 325 or 130 nmoles of either compound was maximal by 24 hours. The effects of these compounds on bone calcium mobilization were also maximal by 24 to 36 hours. When lower doses were tested, 2 nmoles of the 24R, 25-dihydroxycholecalciferol significantly stimulated intestinal calcium transport, whereas 130 nmoles of the S isomer were required for a significant response. Neither steroid had a significant effect on bone calcium mobilization when doses of less than 130 nmoles were given. When chicks received orally 32.5, 325 or 1,625 pmoles of 24R, 25-dihydroxycholecalciferol daily from hatching for 4 weeks, several parameters showed a dose-related response. These included growth, serum calcium, bone ash, renal 25-hydroxycholecalciferol-1-hydroxylase and intestinal vitamin D-dependent calcium binding protein. Rats given 32.5 to 1,625 pmoles of 24R, 25-dihydroxycholecalciferol for 3 or 6 weeks were equivalent to vitamin D-treated controls in terms of growth and serum calcium levels. It is concluded that within the lower dose ranges (2 to 30 pmoles) the R isomer of 24,25-dihydroxycholecalciferol is more active in stimulating intestinal calcium transport than the S isomer but that neither compound increases bone calcium mobilization at these dose levels. Also, the rat is more responsive in terms of growth and serum calcium, to small dialy doses of 24R, 25-dihydroxycholecalciferol than is the chick.", "contents": "Biological activity of 24,25-dihydroxycholecalciferol in chicks and rats. The ability of 24R, 25- and 24S, 25-dihydroxycholecalciferol to stimulate intestinal calcium transport and bone calcium mobilization in chicks was measured. Enhancement of intestinal calcium transport by 325 or 130 nmoles of either compound was maximal by 24 hours. The effects of these compounds on bone calcium mobilization were also maximal by 24 to 36 hours. When lower doses were tested, 2 nmoles of the 24R, 25-dihydroxycholecalciferol significantly stimulated intestinal calcium transport, whereas 130 nmoles of the S isomer were required for a significant response. Neither steroid had a significant effect on bone calcium mobilization when doses of less than 130 nmoles were given. When chicks received orally 32.5, 325 or 1,625 pmoles of 24R, 25-dihydroxycholecalciferol daily from hatching for 4 weeks, several parameters showed a dose-related response. These included growth, serum calcium, bone ash, renal 25-hydroxycholecalciferol-1-hydroxylase and intestinal vitamin D-dependent calcium binding protein. Rats given 32.5 to 1,625 pmoles of 24R, 25-dihydroxycholecalciferol for 3 or 6 weeks were equivalent to vitamin D-treated controls in terms of growth and serum calcium levels. It is concluded that within the lower dose ranges (2 to 30 pmoles) the R isomer of 24,25-dihydroxycholecalciferol is more active in stimulating intestinal calcium transport than the S isomer but that neither compound increases bone calcium mobilization at these dose levels. Also, the rat is more responsive in terms of growth and serum calcium, to small dialy doses of 24R, 25-dihydroxycholecalciferol than is the chick."} {"id": "PMID:178844", "title": "Effects of fluoride and ethane-1-hydroxy-1,1-diphosphonate on bone metabolism in the growing chick.", "content": "White Leghorn cockerols were fed a semipurified diet (containing fluoride at 0 to 800 ppm) from the day of hatching. The birds were also injected daily with solutions containing ethane-1-hydroxy-1,1-diphosphonate (EHDP) at concentrations ranging from 5 to 20 mg as phosphorus/kg of body weight or isotonic saline. Changes in bone mineral composition and plasma Ca, Mg and F were determined as well as alterations in bone pyrophosphatase and the amounts of bone cyclic-3',5'-adenosine monophosphate (cAMP). Since dietary fluoride in high amounts is known to stimulate new bone formation, the purpose of the study was to assess whether a potent inhibitor of mineralization, such as EHDP, might alter the response to high dietary fluoride. Although bone fluoride and magnesium were increased in relationship to dietary fluoride, the administration of EHDP had little effect on these changes at low to moderate levels of fluoride. The levels of soluble bone pyrophosphatase were not greatly influenced by changes in dietary fluoride. Administration of EHDP at 20 mg P/kg, however, typically decreased the levels of bone pyrophosphatase. Bone cAMP did not appear to be influenced by either dietary fluoride or EHDP. Using tissue culture techniques, the effects of fluoride on calcium uptake and release from embryonic chick bone were also studied. The presence of 1 mM fluoride in the medium appeared to stimulate calcium uptake and reduced calcium release from chick bone. In general, the results were in keeping with previous suggestions that the major effect of fluoride on bone is the formation of fluoroapatite and subsequent effects this may have on other metabolic alterations.", "contents": "Effects of fluoride and ethane-1-hydroxy-1,1-diphosphonate on bone metabolism in the growing chick. White Leghorn cockerols were fed a semipurified diet (containing fluoride at 0 to 800 ppm) from the day of hatching. The birds were also injected daily with solutions containing ethane-1-hydroxy-1,1-diphosphonate (EHDP) at concentrations ranging from 5 to 20 mg as phosphorus/kg of body weight or isotonic saline. Changes in bone mineral composition and plasma Ca, Mg and F were determined as well as alterations in bone pyrophosphatase and the amounts of bone cyclic-3',5'-adenosine monophosphate (cAMP). Since dietary fluoride in high amounts is known to stimulate new bone formation, the purpose of the study was to assess whether a potent inhibitor of mineralization, such as EHDP, might alter the response to high dietary fluoride. Although bone fluoride and magnesium were increased in relationship to dietary fluoride, the administration of EHDP had little effect on these changes at low to moderate levels of fluoride. The levels of soluble bone pyrophosphatase were not greatly influenced by changes in dietary fluoride. Administration of EHDP at 20 mg P/kg, however, typically decreased the levels of bone pyrophosphatase. Bone cAMP did not appear to be influenced by either dietary fluoride or EHDP. Using tissue culture techniques, the effects of fluoride on calcium uptake and release from embryonic chick bone were also studied. The presence of 1 mM fluoride in the medium appeared to stimulate calcium uptake and reduced calcium release from chick bone. In general, the results were in keeping with previous suggestions that the major effect of fluoride on bone is the formation of fluoroapatite and subsequent effects this may have on other metabolic alterations."} {"id": "PMID:178845", "title": "Binding of 7-dehydrocholesterol to sterol carrier protein and vitamin D3 effect.", "content": "It was confirmed that delta 5,7-sterol delta 7-reductase activity was suppressed by cholecalciferol (vitamin D3) in the enzyme system consisted of microsomes and sterol carrier protein (SCP). The enzyme activity was significantly decreased in the combination with microsomes obtained from either vitamin D-deficient or vitamin D3-treated rat liver and with SCP obtained from vitamin D3-treated rat. It was also demonstrated by the binding assay of the dextran-charcoal technique that 7-dehydrocholesterol binding to SCP could be specifically displaced by vitamin D3. The inhibition of cholecalciferol on 7-dehydrocholesterol binding to liver SCP was confirmed to be non-competitive inhibition.", "contents": "Binding of 7-dehydrocholesterol to sterol carrier protein and vitamin D3 effect. It was confirmed that delta 5,7-sterol delta 7-reductase activity was suppressed by cholecalciferol (vitamin D3) in the enzyme system consisted of microsomes and sterol carrier protein (SCP). The enzyme activity was significantly decreased in the combination with microsomes obtained from either vitamin D-deficient or vitamin D3-treated rat liver and with SCP obtained from vitamin D3-treated rat. It was also demonstrated by the binding assay of the dextran-charcoal technique that 7-dehydrocholesterol binding to SCP could be specifically displaced by vitamin D3. The inhibition of cholecalciferol on 7-dehydrocholesterol binding to liver SCP was confirmed to be non-competitive inhibition."} {"id": "PMID:178846", "title": "Carbon-13 nuclear magnetic resonance spectra of vitamins D and related compounds.", "content": "1. The natural abundance carbon-13 nmr of vitamins D (D2 and D3) and several isomers (5, 6-trans-vitamin D2, isotachysterol2 and isovitamin D2) have been completely assigned by employing off-resonance noise-decoupling, acetylation shifts, and lanthanide-induced shifts experiments. The last two techniques were especially useful for the present study. 2. Carbon-13 nmr spectral characteristics of the three main conjugated triene moieties (SE-Z-SZ, SE-E-SZ, or SE-E-SE), involved in the molecules of vitamin D and its isomers, were revealed. Thus, the striking dependence of the shieldings on molecular geometries and high sensitivity of the resonances to the environments of conjugated systems were surveyed. 3. Conformational preferences in solutions of the hydroxyl groups in vitamins D2 and D3 as well as 5, 6-trans-vitamin D2 were conveniently determined.", "contents": "Carbon-13 nuclear magnetic resonance spectra of vitamins D and related compounds. 1. The natural abundance carbon-13 nmr of vitamins D (D2 and D3) and several isomers (5, 6-trans-vitamin D2, isotachysterol2 and isovitamin D2) have been completely assigned by employing off-resonance noise-decoupling, acetylation shifts, and lanthanide-induced shifts experiments. The last two techniques were especially useful for the present study. 2. Carbon-13 nmr spectral characteristics of the three main conjugated triene moieties (SE-Z-SZ, SE-E-SZ, or SE-E-SE), involved in the molecules of vitamin D and its isomers, were revealed. Thus, the striking dependence of the shieldings on molecular geometries and high sensitivity of the resonances to the environments of conjugated systems were surveyed. 3. Conformational preferences in solutions of the hydroxyl groups in vitamins D2 and D3 as well as 5, 6-trans-vitamin D2 were conveniently determined."} {"id": "PMID:178847", "title": "Quantitative studies on cell-mediated immunity in the pleural cavity of guinea-pigs.", "content": "Intrapleural injection of PPD into CFA-sensitised guinea-pigs produced a reaction having many of the characteristics of classical delayed hypersensitivity. Quantitative investigations of the time course of this reaction showed that it was typified by an initial delay in the onset of increased vascular permeability, which reached its peak between 12 and 18 hr. The cellular response in the pleural cavity followed a similar pattern, attaining maximum levels between 18 and 24 hr. Mononuclear cells dominated the reaction from 12 to 48 hr. The histological appearance of the lung tissue was also studied. Treatment with Cobra venom factor, a complement-depleting agent, failed to modify this reaction. Cyclic AMP levels were assayed for both the cellular and cell-free exudates.", "contents": "Quantitative studies on cell-mediated immunity in the pleural cavity of guinea-pigs. Intrapleural injection of PPD into CFA-sensitised guinea-pigs produced a reaction having many of the characteristics of classical delayed hypersensitivity. Quantitative investigations of the time course of this reaction showed that it was typified by an initial delay in the onset of increased vascular permeability, which reached its peak between 12 and 18 hr. The cellular response in the pleural cavity followed a similar pattern, attaining maximum levels between 18 and 24 hr. Mononuclear cells dominated the reaction from 12 to 48 hr. The histological appearance of the lung tissue was also studied. Treatment with Cobra venom factor, a complement-depleting agent, failed to modify this reaction. Cyclic AMP levels were assayed for both the cellular and cell-free exudates."} {"id": "PMID:178851", "title": "25-Hydroxycholecalciferol inthe management of rickets associated with extrahepatic biliary atresia.", "content": "In children with extrahepatic biliary atresia, impaired hydroxylation and defective intestinal absorption of cholecalciferol may lead to a deficiency of vitamin D and rickets. The data presented herein demonstrate that in such patients serum levels of vitamin D measured as 25-hydroxycalciferol are reduced. A moderate therapeutic oral dose of 25-hydroxycholecalciferol, by circumventing the hepatic conversion of cholecalciferol to 25-hydroxycholecalciferol, will replete vitamin D stores and maintain the serum concentration of 25-hydroxycalciferol required to prevent or heal rickets in these patients.", "contents": "25-Hydroxycholecalciferol inthe management of rickets associated with extrahepatic biliary atresia. In children with extrahepatic biliary atresia, impaired hydroxylation and defective intestinal absorption of cholecalciferol may lead to a deficiency of vitamin D and rickets. The data presented herein demonstrate that in such patients serum levels of vitamin D measured as 25-hydroxycalciferol are reduced. A moderate therapeutic oral dose of 25-hydroxycholecalciferol, by circumventing the hepatic conversion of cholecalciferol to 25-hydroxycholecalciferol, will replete vitamin D stores and maintain the serum concentration of 25-hydroxycalciferol required to prevent or heal rickets in these patients."} {"id": "PMID:178852", "title": "Evaluation of a live, attenuated respiratory syncytial virus vaccine in infants.", "content": "Respiratory syncytial virus ts-1 is a live attenuated experimental vaccine which was administered intranasally to 25 infants 11 to 19 months of age. Clinical evaluation was carried out following a controlled, double-blind protocol which eliminated observer bias, assessed intercurrent illness, and was designed to detect virus transmission. At the low dose of virus of virus used (100 TCID50) 8 of the 25 recipients were successfully infected with RS virus ts-1 as determined by virus shedding or antibody response.", "contents": "Evaluation of a live, attenuated respiratory syncytial virus vaccine in infants. Respiratory syncytial virus ts-1 is a live attenuated experimental vaccine which was administered intranasally to 25 infants 11 to 19 months of age. Clinical evaluation was carried out following a controlled, double-blind protocol which eliminated observer bias, assessed intercurrent illness, and was designed to detect virus transmission. At the low dose of virus of virus used (100 TCID50) 8 of the 25 recipients were successfully infected with RS virus ts-1 as determined by virus shedding or antibody response."} {"id": "PMID:178853", "title": "HCG + ACTH stimulation of in vitro dehydroepiandrosterone production in human fetal adrenals from precursor cholesterol and delta5-pregnenolone.", "content": "Fetal adrenal glands were obtained from legal abortions in the 14--22 gestational weeks. The adrenal cortex was separated from the medulla using a micromanipulator. The cortex was homogenized in a glass-teflon homogenizer and the microsomal fraction was isolated by centrifugation. Tissue slices were also prepared by the method of Deutsch. The microsomal fraction or the slices were incubated with (4-14C) pregnenolone or (4-14C) cholesterol in the presence of an NADPH regenerating system and oxygen. ACTH or HCG was added. After extraction and paperchromatography radioactivity was determined in a scanner. The conversion of pregnenolone to 17 alpha-hydroxypregnenolone and dehydroepiandrosterone was increased by ACTH. In the presence of HCG dehydroepiandrosterone production only was increased,--and this occurred in slices only. In the microsomal fraction HCG was without effect on steroid biogenesis from dehydroepiandrosterone.", "contents": "HCG + ACTH stimulation of in vitro dehydroepiandrosterone production in human fetal adrenals from precursor cholesterol and delta5-pregnenolone. Fetal adrenal glands were obtained from legal abortions in the 14--22 gestational weeks. The adrenal cortex was separated from the medulla using a micromanipulator. The cortex was homogenized in a glass-teflon homogenizer and the microsomal fraction was isolated by centrifugation. Tissue slices were also prepared by the method of Deutsch. The microsomal fraction or the slices were incubated with (4-14C) pregnenolone or (4-14C) cholesterol in the presence of an NADPH regenerating system and oxygen. ACTH or HCG was added. After extraction and paperchromatography radioactivity was determined in a scanner. The conversion of pregnenolone to 17 alpha-hydroxypregnenolone and dehydroepiandrosterone was increased by ACTH. In the presence of HCG dehydroepiandrosterone production only was increased,--and this occurred in slices only. In the microsomal fraction HCG was without effect on steroid biogenesis from dehydroepiandrosterone."} {"id": "PMID:178855", "title": "Multiple light-evoked conductance changes in the photoreceptors of Hermissenda crassicornis.", "content": "1. Light responses were recorded from the photoreceptors of Hermissenda crassicornis. The response to a flash is a complex potential change involving an initial depolarization, a hyperpolarization, and a depolarizing tail. None of the phases of the response are due to synaptic interactions.2. Polarization of the membrane by extrinsic current indicates that three separate conductance changes are associated with the response. The initial depolarization and hyperpolarization are accompanied by conductance increases and the tail with a conductance decrease. The initial depolarization has a positive reversal potential and the hyperpolarizing and tail phase have a reversal voltage more negative than resting potential.3. The different processes that give rise to the conductance changes have similar spectral sensitivities but are affected unequally by light adaptation. Strong light adaptation reduced the depolarizing phases more than the hyperpolarizing phase, so that following an adapting stimulus the cell responded to illumination with a pure hyperpolarization (isolated hyperpolarization).4. Removal of external Na(+) ions greatly reduced the initial depolarization. In Na(+)-free sea water the cell responds to dim flashes with a slow depolarization (isolated tail) that involves a conductance decrease, and has the same reversal potential as the hyperpolarizing response recorded from light adapted cells.5. The amplitude of the isolated hyperpolarization and tail varied inversely with the external K(+) concentration.6. It is concluded that in Hermissenda photoreceptors light initiates processes that result in three distinct permeability changes. Following a brief flash there is: a rapid and transient increase in Na(+) permeability that is responsible for the initial depolarization, a less rapid increase in K(+) permeability that is responsible for the hyperpolarizing phase, and a delayed decrease in K(+) permeability that gives rise to the depolarizing tail.", "contents": "Multiple light-evoked conductance changes in the photoreceptors of Hermissenda crassicornis. 1. Light responses were recorded from the photoreceptors of Hermissenda crassicornis. The response to a flash is a complex potential change involving an initial depolarization, a hyperpolarization, and a depolarizing tail. None of the phases of the response are due to synaptic interactions.2. Polarization of the membrane by extrinsic current indicates that three separate conductance changes are associated with the response. The initial depolarization and hyperpolarization are accompanied by conductance increases and the tail with a conductance decrease. The initial depolarization has a positive reversal potential and the hyperpolarizing and tail phase have a reversal voltage more negative than resting potential.3. The different processes that give rise to the conductance changes have similar spectral sensitivities but are affected unequally by light adaptation. Strong light adaptation reduced the depolarizing phases more than the hyperpolarizing phase, so that following an adapting stimulus the cell responded to illumination with a pure hyperpolarization (isolated hyperpolarization).4. Removal of external Na(+) ions greatly reduced the initial depolarization. In Na(+)-free sea water the cell responds to dim flashes with a slow depolarization (isolated tail) that involves a conductance decrease, and has the same reversal potential as the hyperpolarizing response recorded from light adapted cells.5. The amplitude of the isolated hyperpolarization and tail varied inversely with the external K(+) concentration.6. It is concluded that in Hermissenda photoreceptors light initiates processes that result in three distinct permeability changes. Following a brief flash there is: a rapid and transient increase in Na(+) permeability that is responsible for the initial depolarization, a less rapid increase in K(+) permeability that is responsible for the hyperpolarizing phase, and a delayed decrease in K(+) permeability that gives rise to the depolarizing tail."} {"id": "PMID:178857", "title": "A contract for co-therapists in group psychotherapy.", "content": "In summary, the relationship between two therapists who choose to conduct a group utilizing the co-therapy model is extremely important. Co-therapy is truly a collaborative effort. It is built on mutual respect and caring. It takes two mature individuals who are willing to work as a team and share in the responsibility for the group. Ten points to consider for a co-therapy contract agreement were proposed to assist in the development of this relationship. If two therapists are able to work together effectively the rewards are endless for both clients and therapists.", "contents": "A contract for co-therapists in group psychotherapy. In summary, the relationship between two therapists who choose to conduct a group utilizing the co-therapy model is extremely important. Co-therapy is truly a collaborative effort. It is built on mutual respect and caring. It takes two mature individuals who are willing to work as a team and share in the responsibility for the group. Ten points to consider for a co-therapy contract agreement were proposed to assist in the development of this relationship. If two therapists are able to work together effectively the rewards are endless for both clients and therapists."} {"id": "PMID:178856", "title": "An in Vitro system for studying insulin release caused by secretory granules-plasma membrane interaction: definition of the system.", "content": "1. An in vitro system is described in which insulin beta-granule-plasma membrane interaction can be studied. 2. The system shows an absolute requirement for physiological amounts of Ca2+ (2 muM) in order for insulin release to proceed. 3. ATP (5 muM) is abot to augment the Ca2+ effect. 4. Glucose (17 mM) alone does not cause insulin release but in the presence of Ca2+ is as effective as ATP. 5. When glucose, ATP and Ca2+ are added together a positive cooperative effect is produced with over 85% of the total insulin, added in the form of beta-granules, being released into the medium in 10 min. 6. The system responds to tolbutamide, in the presence of Ca2+ and ATP, by releasing insulin. 7. Diazoxide, a potent insulin inhibitor in vivo, demonstrates a similar activity in vitro. 8. Various control experiments utilizing alternative membranes, granules, nucleotides, sugars and phosphorylated intermediates of metabolism have all reinforced the specificity of the release mechanisms. 9. These results demonstrate that the in vitro system mimics responses found in the intact organism and can be utilized to dissect the mechanisms associated with exocytosis of insulin granules. 10. Preliminary experiments utilizing adrenaline granules-adrenal plasma membranes and pituitary granules-pituitary plasma membranes suggest that the in vitro system can be extended to all granule secreting processes.", "contents": "An in Vitro system for studying insulin release caused by secretory granules-plasma membrane interaction: definition of the system. 1. An in vitro system is described in which insulin beta-granule-plasma membrane interaction can be studied. 2. The system shows an absolute requirement for physiological amounts of Ca2+ (2 muM) in order for insulin release to proceed. 3. ATP (5 muM) is abot to augment the Ca2+ effect. 4. Glucose (17 mM) alone does not cause insulin release but in the presence of Ca2+ is as effective as ATP. 5. When glucose, ATP and Ca2+ are added together a positive cooperative effect is produced with over 85% of the total insulin, added in the form of beta-granules, being released into the medium in 10 min. 6. The system responds to tolbutamide, in the presence of Ca2+ and ATP, by releasing insulin. 7. Diazoxide, a potent insulin inhibitor in vivo, demonstrates a similar activity in vitro. 8. Various control experiments utilizing alternative membranes, granules, nucleotides, sugars and phosphorylated intermediates of metabolism have all reinforced the specificity of the release mechanisms. 9. These results demonstrate that the in vitro system mimics responses found in the intact organism and can be utilized to dissect the mechanisms associated with exocytosis of insulin granules. 10. Preliminary experiments utilizing adrenaline granules-adrenal plasma membranes and pituitary granules-pituitary plasma membranes suggest that the in vitro system can be extended to all granule secreting processes."} {"id": "PMID:178859", "title": "A simple approach to interrater agreement.", "content": "We have described a simple method for computing a measure of interrater agreement or reliability. This method depends on an experimental design that uses a consensus rating as well as individual ratings. The computations required are counting and percentages; the overall agreement index uses a simple weighting average.", "contents": "A simple approach to interrater agreement. We have described a simple method for computing a measure of interrater agreement or reliability. This method depends on an experimental design that uses a consensus rating as well as individual ratings. The computations required are counting and percentages; the overall agreement index uses a simple weighting average."} {"id": "PMID:178864", "title": "Regulation by FSH and dibutyryl cyclic AMP of the formation of androgen-binding protein in Sertoli cell-enriched cultures.", "content": "Sertoli cell-enriched preparations from testes of 20-day-old rats were cultured in a defined medium in the presence and absence of FSH or dibutyryl cyclic AMP (dcAMP). Androgen-binding activity was assayed in the culture medium, and related to testicular androgen-binding protein (ABP). The production and secretion of ABP by the Sertoli cell-enriched preparation was increased after FSH or dcAMP treatment of the primary culture. It is concluded that ABP is produced by Sertoli cells. The possibility of involvement of other cell types in the testis in ABP production is discussed.", "contents": "Regulation by FSH and dibutyryl cyclic AMP of the formation of androgen-binding protein in Sertoli cell-enriched cultures. Sertoli cell-enriched preparations from testes of 20-day-old rats were cultured in a defined medium in the presence and absence of FSH or dibutyryl cyclic AMP (dcAMP). Androgen-binding activity was assayed in the culture medium, and related to testicular androgen-binding protein (ABP). The production and secretion of ABP by the Sertoli cell-enriched preparation was increased after FSH or dcAMP treatment of the primary culture. It is concluded that ABP is produced by Sertoli cells. The possibility of involvement of other cell types in the testis in ABP production is discussed."} {"id": "PMID:178868", "title": "Reversible inhibition of the motility of human spermatozoa by tetraphenylboron.", "content": "The motility of washed suspensions of human spermatozoa was completely inhibited by tetraphenylboron at concentrations that had little effect on sperm energy metabolism. The inhibition of motility was reversed by quaternary ammonium salts, albumin, caffeine, dibutyryl cyclic AMP and potassium ions. The addition of ouabain to cells redndered immotile by tetraphenylboron prevented reinitiation of motility by potassium but not by the other compounds. These observations, together with the effect of tetraphenylboron on the fluorescence of sperm suspensions treated with 1-anilinonaphthalene 8-sulphonic acid, suggest that the binding of tetraphenylboron to sites on the sperm plasma membrane is involved in the inhibition of sperm motility and the cyclic AMP may be involved in the regulation of ion transport across the plasma membrane.", "contents": "Reversible inhibition of the motility of human spermatozoa by tetraphenylboron. The motility of washed suspensions of human spermatozoa was completely inhibited by tetraphenylboron at concentrations that had little effect on sperm energy metabolism. The inhibition of motility was reversed by quaternary ammonium salts, albumin, caffeine, dibutyryl cyclic AMP and potassium ions. The addition of ouabain to cells redndered immotile by tetraphenylboron prevented reinitiation of motility by potassium but not by the other compounds. These observations, together with the effect of tetraphenylboron on the fluorescence of sperm suspensions treated with 1-anilinonaphthalene 8-sulphonic acid, suggest that the binding of tetraphenylboron to sites on the sperm plasma membrane is involved in the inhibition of sperm motility and the cyclic AMP may be involved in the regulation of ion transport across the plasma membrane."} {"id": "PMID:178869", "title": "Investigations on adenosine 3',5'-monophosphate phosphodiesterase in ram semen and initial characterization of a sperm-specific isoenzyme.", "content": "Phosphodiesterase is shown to occur in ram semen, and its activity to be higher in spermatozoa than in seminal plasma. Using similar substrate levels, the rate at which adenosine 3',5'-monophosphate (cyclic AMP) is metabolized by phosphodiesterase in spermatozoa is about 100 times higher than that of cyclic AMP synthesis by adenylate cyclase. In spermatozoa, phosphodiesterase is present partly in a soluble form, and partly bound; both forms can be extracted by sonication. The soluble enzyme (pH optimum 8-0, Km = 1-5 muM, mol. wt 165,000) occurs as a single isoenzyme, as shown by polyacrylamide gel electrophoresis and anion-exchange chromatography; this isoenzyme appears to be specific for spermatozoa and its formation in the testis coincides with the appearance of spermatozoa. The bound sperm enzyme has been solubilized with Trion X-100; it is a single isoenzyme (pH optimum 8-0, mol. wt 165,000) which is electrophoretically different from the soluble form, but similar to the phosphodiesterase found in other tissues. Seminal plasma phosphodiesterase (pH optimum 8-8, mol. wt 165,000) is present in the form of three isoenzymes; all three are different from the two forms of sperm phosphodiesterase, but are similar to the isoenzymes found in certain male accessory organs.", "contents": "Investigations on adenosine 3',5'-monophosphate phosphodiesterase in ram semen and initial characterization of a sperm-specific isoenzyme. Phosphodiesterase is shown to occur in ram semen, and its activity to be higher in spermatozoa than in seminal plasma. Using similar substrate levels, the rate at which adenosine 3',5'-monophosphate (cyclic AMP) is metabolized by phosphodiesterase in spermatozoa is about 100 times higher than that of cyclic AMP synthesis by adenylate cyclase. In spermatozoa, phosphodiesterase is present partly in a soluble form, and partly bound; both forms can be extracted by sonication. The soluble enzyme (pH optimum 8-0, Km = 1-5 muM, mol. wt 165,000) occurs as a single isoenzyme, as shown by polyacrylamide gel electrophoresis and anion-exchange chromatography; this isoenzyme appears to be specific for spermatozoa and its formation in the testis coincides with the appearance of spermatozoa. The bound sperm enzyme has been solubilized with Trion X-100; it is a single isoenzyme (pH optimum 8-0, mol. wt 165,000) which is electrophoretically different from the soluble form, but similar to the phosphodiesterase found in other tissues. Seminal plasma phosphodiesterase (pH optimum 8-8, mol. wt 165,000) is present in the form of three isoenzymes; all three are different from the two forms of sperm phosphodiesterase, but are similar to the isoenzymes found in certain male accessory organs."} {"id": "PMID:178870", "title": "Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine.", "content": "Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, \"uracil anhydride\") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (4c) thus prepared from the protected sugar 3c, 1-O-acetyl-2,3,5-tri-O-(2,2,2-trichloroethoxycarbonyl)ribofuranose, gave, on removal of the protecting groups with zinc dust,3-(beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (1). The structure of 1 was confirmed by uv, ir, NMR, and CD spectral data and was shown to be an N nucleoside. Uracil anhydride, 2, and, to a lesser extent, its ribonucleoside 1 exert a moderate growth inhibition of mouse leukemia L5178Y, HeLa, and Novikoff hepatoma cells i- culture. Both compounds produce weak inhibition of vaccinia viral replication in HeLa cells.", "contents": "Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine. Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, \"uracil anhydride\") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (4c) thus prepared from the protected sugar 3c, 1-O-acetyl-2,3,5-tri-O-(2,2,2-trichloroethoxycarbonyl)ribofuranose, gave, on removal of the protecting groups with zinc dust,3-(beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (1). The structure of 1 was confirmed by uv, ir, NMR, and CD spectral data and was shown to be an N nucleoside. Uracil anhydride, 2, and, to a lesser extent, its ribonucleoside 1 exert a moderate growth inhibition of mouse leukemia L5178Y, HeLa, and Novikoff hepatoma cells i- culture. Both compounds produce weak inhibition of vaccinia viral replication in HeLa cells."} {"id": "PMID:178871", "title": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. 6. Synthesis and biological evaluation of some 3'-acyl derivatives of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine hydrochloride.", "content": "The reactions of cytidine with 22 different 2-O-acyloxyisobutyril chlorides lead to the isolation of the corresponding 2,2'-anhydro-1-(3'-O-acyl-beta-d-arabinofuranosyl)cytosine hydrochlorides 9. These compounds, which all show cytotoxicity against HeLa cells in tissue culture, have been examined for antiviral and antileukemic activity. Activity against DNA viruses (vaccinia and Herpes) in tissue culture is maximal in compounds containing acyl groups with 8--12 carbon atoms. Activity against L1210 leukemia in mice varies markedly according to the length of the acyl groups, and high activities were observed in the case of long-chain (C16--C22) esters. The reaction between cytidine and O-acetylsalicyloyl chloride provides an alternate route for the synthesis of 3'-O-Ac cycloC hydrochloride.", "contents": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. 6. Synthesis and biological evaluation of some 3'-acyl derivatives of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine hydrochloride. The reactions of cytidine with 22 different 2-O-acyloxyisobutyril chlorides lead to the isolation of the corresponding 2,2'-anhydro-1-(3'-O-acyl-beta-d-arabinofuranosyl)cytosine hydrochlorides 9. These compounds, which all show cytotoxicity against HeLa cells in tissue culture, have been examined for antiviral and antileukemic activity. Activity against DNA viruses (vaccinia and Herpes) in tissue culture is maximal in compounds containing acyl groups with 8--12 carbon atoms. Activity against L1210 leukemia in mice varies markedly according to the length of the acyl groups, and high activities were observed in the case of long-chain (C16--C22) esters. The reaction between cytidine and O-acetylsalicyloyl chloride provides an alternate route for the synthesis of 3'-O-Ac cycloC hydrochloride."} {"id": "PMID:178872", "title": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. 7. Synthesis and biological evaluation of some 2,2'-anhydro-1(3',5'-di-O-acyl-beta-D-arabinofuranosyl)cytosine hydrochlorides.", "content": "The direct acylation of 2,2'-anhydro-1(beta-D-arabinofuranosyl)cytosine hydrochloride (cycloC) with a homologous series of saturated and unsaturated acyl chlorides in dimethylacetamide has been investigated. Such acylation reactions have made available a considerable number of 3',5'-diesters of cycloC that have been examined for biological activities. The compounds all show cytotoxicity against HeLa cells in tissue culture, and with the exception of the highly insoluble long-chain diesters (C16--C22), show pronounced activity against vaccinia and Herpes simplex viruses. Against L1210 leukemia in mice the compounds show varied activities, the C12--C14 saturated diesters and the C18--C22 unsaturated diesters being highly effective. Other diesters, varying by only a few methylene groups, show dramatically different results.", "contents": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. 7. Synthesis and biological evaluation of some 2,2'-anhydro-1(3',5'-di-O-acyl-beta-D-arabinofuranosyl)cytosine hydrochlorides. The direct acylation of 2,2'-anhydro-1(beta-D-arabinofuranosyl)cytosine hydrochloride (cycloC) with a homologous series of saturated and unsaturated acyl chlorides in dimethylacetamide has been investigated. Such acylation reactions have made available a considerable number of 3',5'-diesters of cycloC that have been examined for biological activities. The compounds all show cytotoxicity against HeLa cells in tissue culture, and with the exception of the highly insoluble long-chain diesters (C16--C22), show pronounced activity against vaccinia and Herpes simplex viruses. Against L1210 leukemia in mice the compounds show varied activities, the C12--C14 saturated diesters and the C18--C22 unsaturated diesters being highly effective. Other diesters, varying by only a few methylene groups, show dramatically different results."} {"id": "PMID:178873", "title": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. Synthesis and biological evaluation of some 3\"-acyl and 3',5'-diacyl derivatives of 1-beta-D-arabinofuranosylcytosine.", "content": "Previous papers in this series have described efficient syntheses of 3'-O-acyl and 3',5'-di-O-acyl and 3',5'-di-O-acyl derivatives of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine hydrochloride (1,3). It has now been shown that the 2,2'-anhydro linkage in 1 and 3 can be selectively and efficiently cleaved by treatment with a mixture of pyridine and methanol giving the corresponding 3'-O-acyl derivatives of 1-beta-D-arabinofuranosylcytosine (2,4). The selective hydrolysis of the more soluble derivatives can also be achieved using either aqueous pyridine or a mixture of sodium carbonate and sodium bicarbonate in aqueous dioxane. Using the above procedures 3'-O-acyl araCs and 3',5'-di-O-acyl araCs with saturated or unsaturated ester groups containg from 2 to 22 carbon atoms have been prepared, and these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity against L1210 leukemia in mice. Many of the compounds show high anti-L1210 activity relative to araC itself.", "contents": "Reactions of 2-acyloxyisobutyryl halides with nucleosides. Synthesis and biological evaluation of some 3\"-acyl and 3',5'-diacyl derivatives of 1-beta-D-arabinofuranosylcytosine. Previous papers in this series have described efficient syntheses of 3'-O-acyl and 3',5'-di-O-acyl and 3',5'-di-O-acyl derivatives of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine hydrochloride (1,3). It has now been shown that the 2,2'-anhydro linkage in 1 and 3 can be selectively and efficiently cleaved by treatment with a mixture of pyridine and methanol giving the corresponding 3'-O-acyl derivatives of 1-beta-D-arabinofuranosylcytosine (2,4). The selective hydrolysis of the more soluble derivatives can also be achieved using either aqueous pyridine or a mixture of sodium carbonate and sodium bicarbonate in aqueous dioxane. Using the above procedures 3'-O-acyl araCs and 3',5'-di-O-acyl araCs with saturated or unsaturated ester groups containg from 2 to 22 carbon atoms have been prepared, and these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity against L1210 leukemia in mice. Many of the compounds show high anti-L1210 activity relative to araC itself."} {"id": "PMID:178881", "title": "A comparison of the metabolic effects of bovine growth hormone and growth factor from Spirometra mansonoides on rat liver in vivo.", "content": "The effects of bovine growth hormone(GH) and Spirometra growth factor (SGF) on the in vivo concentrationions of glycolytic and citricacid (TCA) cycle intermediates in rat liver were investigated. The effects of these agents on the mitochondrial and cytoplasmic redox states, liver phosphorylation states, and adenylate kinase activity were also evaluated. The effects of SGF were studied in both normal and hypophysectomized rats,wheras GH effects ere examined only in hypophysectomized rats. Growth homrone(0.25mg/rat) was injected dayily for 9 days...", "contents": "A comparison of the metabolic effects of bovine growth hormone and growth factor from Spirometra mansonoides on rat liver in vivo. The effects of bovine growth hormone(GH) and Spirometra growth factor (SGF) on the in vivo concentrationions of glycolytic and citricacid (TCA) cycle intermediates in rat liver were investigated. The effects of these agents on the mitochondrial and cytoplasmic redox states, liver phosphorylation states, and adenylate kinase activity were also evaluated. The effects of SGF were studied in both normal and hypophysectomized rats,wheras GH effects ere examined only in hypophysectomized rats. Growth homrone(0.25mg/rat) was injected dayily for 9 days..."} {"id": "PMID:178882", "title": "An adrenergic mechanism for visual neuroregulation.", "content": "Studies of the diffuse electroretinogram (ERG) and evoked reponses in the optic lobe in the baby chick have shown that epinephrine produces changes in both. Epinephrine produces enhancement of the a-wave and depression of the b- and d-waves in both intact and isolated eyes. In the optic lobe it produces enhancement of both components of the evoked response. The presence of epinephrine in the vertebrate retina and the optic lobe of chicks suggests that these changes may reflect the involvement of epinephrine in synaptic transmission.", "contents": "An adrenergic mechanism for visual neuroregulation. Studies of the diffuse electroretinogram (ERG) and evoked reponses in the optic lobe in the baby chick have shown that epinephrine produces changes in both. Epinephrine produces enhancement of the a-wave and depression of the b- and d-waves in both intact and isolated eyes. In the optic lobe it produces enhancement of both components of the evoked response. The presence of epinephrine in the vertebrate retina and the optic lobe of chicks suggests that these changes may reflect the involvement of epinephrine in synaptic transmission."} {"id": "PMID:178883", "title": "Neurochemical changes in the cat's spinal cord due to orthodromic tetanic stimuli. I: phospholipids.", "content": "Posttetanic potentiation of monosynaptic reflexes has been used as a paradigm for neuronal plasticity. The explanation for this phenomenon is an increased responsiveness of the synaptic junctions. This would basically require chemical changes of the nervous structures involved. The ventral horn area of the spinal cord was therefore analyzed neurochemically. The determination of the phospholipids revealed an alteration of their composition. Sphingomyelin, phosphatidylcholine and phosphatidylinositide/serine behaved differently, whereas phosphatidylethanolamine and the total phospholipid content remained unchanged.", "contents": "Neurochemical changes in the cat's spinal cord due to orthodromic tetanic stimuli. I: phospholipids. Posttetanic potentiation of monosynaptic reflexes has been used as a paradigm for neuronal plasticity. The explanation for this phenomenon is an increased responsiveness of the synaptic junctions. This would basically require chemical changes of the nervous structures involved. The ventral horn area of the spinal cord was therefore analyzed neurochemically. The determination of the phospholipids revealed an alteration of their composition. Sphingomyelin, phosphatidylcholine and phosphatidylinositide/serine behaved differently, whereas phosphatidylethanolamine and the total phospholipid content remained unchanged."} {"id": "PMID:178885", "title": "Synethesis and integration of viral DNA in chicken cells at different time after infection with various multiplicities of avian oncornavirus.", "content": "To see if integration of the provirus resulting from RNA tumor virus infection is limited to specific sites in the cell DNA, the variation in the number of copies of virus-specific DNA produced and integrated in chicken embryo fibroblasts after RAV-2 infection with different multiplicities has been determined at short times, long times, and several transfers after infection. The number of copies of viral DNA in cells was determined by initial hybridization kinetics of single-stranded viral complementary DNA with a moderate excess of cell DNA. The approach took into account the different sizes of cell DNA and complementary DNA in the hybridization mixture. It was found that uninfected chicken embryo fibroblasts have approximately seven copies, part haploid genome of DNA sequences homologous to part of the Rous-association virus 2 (RAV-2) genome. Infection with RAV-2 adds additional copies, and different sequences, of RAV -2- specific DNA. By 13 h postinfection, there are 3 to 10 additional copies per haploid genome. This number can not be increased by increasing the multiplicity of infection, and stays relatively constant up to 20 h postinfection, when some of the additional viral DNA is integrated. Between 20 and 40 h postinfection, the cells accumulated up to 100 copies per haploid genome of viral DNA. Most of these are unintegrated. This number decreases with cell transfer, until cells are left with one to three copies of additional viral DNA sequences per haploid genome, of which most are integrated. The finding that viral infection causes the permanent addition of one to three copies of integrated viral DNA, despite the cells being confronted with up to 100 copies per haploid genome after infection, is consistent with a hypothesis that chicken cells contain a limited number of specific integration sites for the oncornavirus genome.", "contents": "Synethesis and integration of viral DNA in chicken cells at different time after infection with various multiplicities of avian oncornavirus. To see if integration of the provirus resulting from RNA tumor virus infection is limited to specific sites in the cell DNA, the variation in the number of copies of virus-specific DNA produced and integrated in chicken embryo fibroblasts after RAV-2 infection with different multiplicities has been determined at short times, long times, and several transfers after infection. The number of copies of viral DNA in cells was determined by initial hybridization kinetics of single-stranded viral complementary DNA with a moderate excess of cell DNA. The approach took into account the different sizes of cell DNA and complementary DNA in the hybridization mixture. It was found that uninfected chicken embryo fibroblasts have approximately seven copies, part haploid genome of DNA sequences homologous to part of the Rous-association virus 2 (RAV-2) genome. Infection with RAV-2 adds additional copies, and different sequences, of RAV -2- specific DNA. By 13 h postinfection, there are 3 to 10 additional copies per haploid genome. This number can not be increased by increasing the multiplicity of infection, and stays relatively constant up to 20 h postinfection, when some of the additional viral DNA is integrated. Between 20 and 40 h postinfection, the cells accumulated up to 100 copies per haploid genome of viral DNA. Most of these are unintegrated. This number decreases with cell transfer, until cells are left with one to three copies of additional viral DNA sequences per haploid genome, of which most are integrated. The finding that viral infection causes the permanent addition of one to three copies of integrated viral DNA, despite the cells being confronted with up to 100 copies per haploid genome after infection, is consistent with a hypothesis that chicken cells contain a limited number of specific integration sites for the oncornavirus genome."} {"id": "PMID:178886", "title": "RNA metabolism of murine leukemia virus. III. Identification and quantitation of endogenous virus-specific mRNA in the uninfected BALB/c cell line JLS-V9.", "content": "mRNA containing type C endogenous virus-specific sequences was indentified in JLS-V9 cells (an uninfected BALB/c-derived cell line) by annealing extracted RNA with 3H-labeled virus-specific DNA. The criterion for virus-specific RNA being mRNA was that it co-sedimented with polyribosomes in a sucrose gradient and that it changed to lower sedimentation value if polyribosomes were disagregated prior to centrifugation. It was not possible to identify virus-specific mRNA in unfractionated cytoplasm from JLS-V9 cells since large amounts of virus-specific ribonucleoprotein which was not mRNA had sedimentation values similar to polyribosomes and obscured the analysis. Virus-specific mRNA could be readily identified in polyribosomes which had been purified through a step gradient of 1 and 2 M sucrose, and consisted of two species with sedimentation values of 38S and 27S. The amount of virus-specific RNA in different JLS-V9 cell fractions was quantitated in comparison to cell fractions obtained from M-MuLV clone no. 1 cells (a line of NIH 3T3 cells producing Moloney murine leukemia virus). Approximately 40% of the total virus-specific mRNA was recovered in the purified polyribosomes in M-MuLV no. 1 cells. The amount of virus-specific RNA on polyribosomes appeared to be quite similar for JLS-V9 cells and M-MuLV clone no.1 cells . In contrast, the level of virus-specific protein in JLS-V9 cells (as monitored by radioimmunoassay of the internal structural protein p30) was less than 2% the level in the M-MuLV clone no. 1 cells.", "contents": "RNA metabolism of murine leukemia virus. III. Identification and quantitation of endogenous virus-specific mRNA in the uninfected BALB/c cell line JLS-V9. mRNA containing type C endogenous virus-specific sequences was indentified in JLS-V9 cells (an uninfected BALB/c-derived cell line) by annealing extracted RNA with 3H-labeled virus-specific DNA. The criterion for virus-specific RNA being mRNA was that it co-sedimented with polyribosomes in a sucrose gradient and that it changed to lower sedimentation value if polyribosomes were disagregated prior to centrifugation. It was not possible to identify virus-specific mRNA in unfractionated cytoplasm from JLS-V9 cells since large amounts of virus-specific ribonucleoprotein which was not mRNA had sedimentation values similar to polyribosomes and obscured the analysis. Virus-specific mRNA could be readily identified in polyribosomes which had been purified through a step gradient of 1 and 2 M sucrose, and consisted of two species with sedimentation values of 38S and 27S. The amount of virus-specific RNA in different JLS-V9 cell fractions was quantitated in comparison to cell fractions obtained from M-MuLV clone no. 1 cells (a line of NIH 3T3 cells producing Moloney murine leukemia virus). Approximately 40% of the total virus-specific mRNA was recovered in the purified polyribosomes in M-MuLV no. 1 cells. The amount of virus-specific RNA on polyribosomes appeared to be quite similar for JLS-V9 cells and M-MuLV clone no.1 cells . In contrast, the level of virus-specific protein in JLS-V9 cells (as monitored by radioimmunoassay of the internal structural protein p30) was less than 2% the level in the M-MuLV clone no. 1 cells."} {"id": "PMID:178887", "title": "State of the viral DNA in rat cells transformed by polyoma virus. I. Virus rescue and the presence of nonintergrated viral DNA molecules.", "content": "The interaction of polyoma virus with a continuous line of rat cells was studied. Infection of these cells with polyoma did not cause virus multiplication but induced transformation. Transformed cells did not produce infectious virus, but in all clones tested virus was rescuable upon fusion with permissive mouse cells. Transformed rat cells contained, in addition to integrated viral genomes, 20 to 50 copies of nonintegrated viral DNA equivalents per cell (average). \"Free\" viral DNA molecules were also found in cells transformed by the ts-a and ts-8 polyoma mutants and kept at 33 C. This was not due to a virus carrier state, since the number of nonintegrated viral DNA molecules was found to be unchanged when cells were grown in the presence of antipolyoma serum. Recloning of the transformed cell lines produced subclones, which also contained free viral DNA. Most of these molecules were supercoiled and were found in the muclei of the transformed cells. The nonintegrated viral DNA is infectious. Its specifici infectivity is, however, about 100-fold lower than that of polyoma DNA extracted from productively infected cells, suggesting that these molecules contain a large proportion of defectives.", "contents": "State of the viral DNA in rat cells transformed by polyoma virus. I. Virus rescue and the presence of nonintergrated viral DNA molecules. The interaction of polyoma virus with a continuous line of rat cells was studied. Infection of these cells with polyoma did not cause virus multiplication but induced transformation. Transformed cells did not produce infectious virus, but in all clones tested virus was rescuable upon fusion with permissive mouse cells. Transformed rat cells contained, in addition to integrated viral genomes, 20 to 50 copies of nonintegrated viral DNA equivalents per cell (average). \"Free\" viral DNA molecules were also found in cells transformed by the ts-a and ts-8 polyoma mutants and kept at 33 C. This was not due to a virus carrier state, since the number of nonintegrated viral DNA molecules was found to be unchanged when cells were grown in the presence of antipolyoma serum. Recloning of the transformed cell lines produced subclones, which also contained free viral DNA. Most of these molecules were supercoiled and were found in the muclei of the transformed cells. The nonintegrated viral DNA is infectious. Its specifici infectivity is, however, about 100-fold lower than that of polyoma DNA extracted from productively infected cells, suggesting that these molecules contain a large proportion of defectives."} {"id": "PMID:178888", "title": "Intracellular distribution and sedimentation properties of virus-specific RNA in two clones of BHK cells transformed by polyoma virus.", "content": "The virus-specific RNA in two independently derived clones of polyoma virus-transformed hamster cells was studied by hybridizing labeled RNA, with excess purified polyoma DNA, immoblized on filters. In one clone (PyBHK1), less than 25% of the total labeled virus-specific RNA was found in the cytoplasm, irrespective of the labeling time. In the other clone (PyBHK2), it was estimated that 39% of the total virus-specific RNA was present inthe cytoplasm after labeling for 3 h. Both the proportion of radioactive label incorporated into virus-specific RNA and the sedimentation pattern of total virus-specific RNA differed markedly between PyBHK and PyBHK2. Most of the virus-specific RNA of PyBHK1 sedimented in the range 25S-35S, whereas a prominent 18S component was present in PyBHK2. Most of the cytoplasmic virus-specific RNA in both clones sedimented at 18S-19S. The sedimentation patterns of virus-specific RNA from whole cells and from washed nuclei of PyBHK1 were closely similar: it was estimated from sedimentation analysis in dimethyl sulfoxide that the molecular weight of 50% of this RNA was within the range 1.1 X10(6) to 2.9 X 10(6). These results, demonstrating the accumulation of virus-specific RNA within the nucleus in at least one virus-transformed cell line, indicate that the large virus-specific RNA previously described in the nuclei of transformed cells may not have represented precursors of virus-specific mRNA.", "contents": "Intracellular distribution and sedimentation properties of virus-specific RNA in two clones of BHK cells transformed by polyoma virus. The virus-specific RNA in two independently derived clones of polyoma virus-transformed hamster cells was studied by hybridizing labeled RNA, with excess purified polyoma DNA, immoblized on filters. In one clone (PyBHK1), less than 25% of the total labeled virus-specific RNA was found in the cytoplasm, irrespective of the labeling time. In the other clone (PyBHK2), it was estimated that 39% of the total virus-specific RNA was present inthe cytoplasm after labeling for 3 h. Both the proportion of radioactive label incorporated into virus-specific RNA and the sedimentation pattern of total virus-specific RNA differed markedly between PyBHK and PyBHK2. Most of the virus-specific RNA of PyBHK1 sedimented in the range 25S-35S, whereas a prominent 18S component was present in PyBHK2. Most of the cytoplasmic virus-specific RNA in both clones sedimented at 18S-19S. The sedimentation patterns of virus-specific RNA from whole cells and from washed nuclei of PyBHK1 were closely similar: it was estimated from sedimentation analysis in dimethyl sulfoxide that the molecular weight of 50% of this RNA was within the range 1.1 X10(6) to 2.9 X 10(6). These results, demonstrating the accumulation of virus-specific RNA within the nucleus in at least one virus-transformed cell line, indicate that the large virus-specific RNA previously described in the nuclei of transformed cells may not have represented precursors of virus-specific mRNA."} {"id": "PMID:178889", "title": "Inherited resistance to N- and B-tropic murine leukemia viruses in vitro: titration patterns in strains SIM and SIM.R congenic at the Fv-1 locus.", "content": "We have investigated the titration patterns of murine leukemia viruses on mouse embryo cultures derived from a pair of congenic strains differing at the Fv-1 locus. XC plaque and infectious center assays carried out with N- and B-tropic viruses on both SIM (Fv-1nn) and SIM.R(Fv-1bb) host cells yielded results that were best approximated by Poisson one-hit curves. Titration curves of N-tropic virus by direct XC plaque assay were linear and parallel on the different hosts, with titers 1.8 to 2.7 log10 lower on SIM.R and on (SIM X SIM.R)F1 than on SIM cells; similar linear and parallel curves were found for B-tropic virus, with titers 1.4 to 2.0 log10 lower on SIM and (SIM XSIM-R)F1 than on SIM-R cells. In the infectious center assays, the proportion of infected cells was linearly related to multiplicity of infection on both permissive (N- on SIM and B- on SIM.R) restrictive (B- on SIM and N- on SIM.R) genotypes at multiplicities of infection below 0.5; the line relating the variables was about 1 log10 lower in the restrictive than in the permissive situations. At multiplicities of infection where the proportion of infected cells reached a plateau, differences between the results on permissive and restrictive genotypes were considerably reduced. This appeared to be due to the action of non-Fv-1 factors in permissive host. We conclude that the major action of the restrictive allele at the Fv-1 locus in this system is to reduce the probability of successful murine leukemia virus infection without a change in hitness.", "contents": "Inherited resistance to N- and B-tropic murine leukemia viruses in vitro: titration patterns in strains SIM and SIM.R congenic at the Fv-1 locus. We have investigated the titration patterns of murine leukemia viruses on mouse embryo cultures derived from a pair of congenic strains differing at the Fv-1 locus. XC plaque and infectious center assays carried out with N- and B-tropic viruses on both SIM (Fv-1nn) and SIM.R(Fv-1bb) host cells yielded results that were best approximated by Poisson one-hit curves. Titration curves of N-tropic virus by direct XC plaque assay were linear and parallel on the different hosts, with titers 1.8 to 2.7 log10 lower on SIM.R and on (SIM X SIM.R)F1 than on SIM cells; similar linear and parallel curves were found for B-tropic virus, with titers 1.4 to 2.0 log10 lower on SIM and (SIM XSIM-R)F1 than on SIM-R cells. In the infectious center assays, the proportion of infected cells was linearly related to multiplicity of infection on both permissive (N- on SIM and B- on SIM.R) restrictive (B- on SIM and N- on SIM.R) genotypes at multiplicities of infection below 0.5; the line relating the variables was about 1 log10 lower in the restrictive than in the permissive situations. At multiplicities of infection where the proportion of infected cells reached a plateau, differences between the results on permissive and restrictive genotypes were considerably reduced. This appeared to be due to the action of non-Fv-1 factors in permissive host. We conclude that the major action of the restrictive allele at the Fv-1 locus in this system is to reduce the probability of successful murine leukemia virus infection without a change in hitness."} {"id": "PMID:178890", "title": "Fractionation of DNA nucleotide transcripts from Moloney sarcoma virus and isolation of sarcoma virus-specific complementary DNA.", "content": "Radioactive DNA complementary to nucleotide sequences in Moloney murine sarcoma virus (MSV) and Moloney leukemia virus (M-MuLV) complex was made by the endogenous reverse transcriptase reaction. These virus stocks contained a threefold excess of MSV over M-MuLV as measured by biological assay. The complementary DNA was an accurate copy of the viral RNA in that 86% of 35S viral RNA hybridized with complementary (cDNA) DNA at a 1.5 to 1 cDNA-RNA molar ratio. The complementary DNA, of a 4-6S size, was fractionated by sequential absorptions with MulV and the feline leukemia virus pseudotype of MSV, [MSV(FeLV)] RNA. In this manner three sets of nucleotide sequences whichrepresent different portions of the MSV viral complex were obtained: a sarcoma virus-specific fraction (cDNAsarc) with sequences that had no homology to M-MuLV RNA but which hybridized to MSV (FeLV) RNA, a sarcoma-leukemia fraction (cDNA common) with sequences common to MSV as well as M-MuLV viral RNA, and a cDNAleuk representing those nucleotide sequences found only in M-MuLV. Hybridization of MSV-MuLV viral 35S RNA with a threefold molar excess of cDNA's revealed that approximately 20% was hybridized with cDNAsarc, whereas approximately 75% was hybridized with cDNAcommon. M-MuLV 35S RNA alone did not hybridize with cDNAsarc but did hybridize 40 and 50% with cDNAleuk and cDNAcommon, respectively. The cDNAsarc represents about 25% of the total MSV sequences, whereas the cDNAcommon represents the remainder of the MSV virus genome. Some cDNAcommon sequences were shared by two other sarcoma viruses and several distinctly different isolates of MulV. In contrast, the MSV \"sarc\" sequences had little or no homology with two other murine sarcoma virus isolates.", "contents": "Fractionation of DNA nucleotide transcripts from Moloney sarcoma virus and isolation of sarcoma virus-specific complementary DNA. Radioactive DNA complementary to nucleotide sequences in Moloney murine sarcoma virus (MSV) and Moloney leukemia virus (M-MuLV) complex was made by the endogenous reverse transcriptase reaction. These virus stocks contained a threefold excess of MSV over M-MuLV as measured by biological assay. The complementary DNA was an accurate copy of the viral RNA in that 86% of 35S viral RNA hybridized with complementary (cDNA) DNA at a 1.5 to 1 cDNA-RNA molar ratio. The complementary DNA, of a 4-6S size, was fractionated by sequential absorptions with MulV and the feline leukemia virus pseudotype of MSV, [MSV(FeLV)] RNA. In this manner three sets of nucleotide sequences whichrepresent different portions of the MSV viral complex were obtained: a sarcoma virus-specific fraction (cDNAsarc) with sequences that had no homology to M-MuLV RNA but which hybridized to MSV (FeLV) RNA, a sarcoma-leukemia fraction (cDNA common) with sequences common to MSV as well as M-MuLV viral RNA, and a cDNAleuk representing those nucleotide sequences found only in M-MuLV. Hybridization of MSV-MuLV viral 35S RNA with a threefold molar excess of cDNA's revealed that approximately 20% was hybridized with cDNAsarc, whereas approximately 75% was hybridized with cDNAcommon. M-MuLV 35S RNA alone did not hybridize with cDNAsarc but did hybridize 40 and 50% with cDNAleuk and cDNAcommon, respectively. The cDNAsarc represents about 25% of the total MSV sequences, whereas the cDNAcommon represents the remainder of the MSV virus genome. Some cDNAcommon sequences were shared by two other sarcoma viruses and several distinctly different isolates of MulV. In contrast, the MSV \"sarc\" sequences had little or no homology with two other murine sarcoma virus isolates."} {"id": "PMID:178891", "title": "Deletion mapping of moloney type C virus: polypeptide and nucleic acid expression in different transforming virus isolates.", "content": "The viral polypeptides and viral RNA present in cells transformed by various replication-defective type C viruses derived from Maloney murine leukemia virus were examined. Different portions of the Maloney type C viral genome were retained in the different transforming viruses, thus providing an opportunity for deletion mapping of the Moloney type C genome. DNA transcripts were prepared that are complementary to three distinct nonoverlapping portions of the Moloney viral geonome. Based on an anlysis of the polypeptides produced in the different transformed cells, one complementary DNA apparently respresents sequences coding for Moloney gp70; one complementary DNA represents a region of the Moloney genome common to all of the transforming viruses examined, and one complementary DNA represents the sequences for p30, p15, p10,12. A partial map of the different replication-defective transforming viruses is suggested.", "contents": "Deletion mapping of moloney type C virus: polypeptide and nucleic acid expression in different transforming virus isolates. The viral polypeptides and viral RNA present in cells transformed by various replication-defective type C viruses derived from Maloney murine leukemia virus were examined. Different portions of the Maloney type C viral genome were retained in the different transforming viruses, thus providing an opportunity for deletion mapping of the Moloney type C genome. DNA transcripts were prepared that are complementary to three distinct nonoverlapping portions of the Moloney viral geonome. Based on an anlysis of the polypeptides produced in the different transformed cells, one complementary DNA apparently respresents sequences coding for Moloney gp70; one complementary DNA represents a region of the Moloney genome common to all of the transforming viruses examined, and one complementary DNA represents the sequences for p30, p15, p10,12. A partial map of the different replication-defective transforming viruses is suggested."} {"id": "PMID:178892", "title": "Viral glycoprotein synthesis studies in an established line of Japanese quail embryo cells infected with the Bryan high-titer strain of Rous sarcoma virus.", "content": "Although a glycoprotein with an approximate molecular weight of 43,000 is associated with purified virions of the Bryan high-titer strain of Rous sarcoma virus propagated on R(-)Q cells, these virions lack gp85, the major glycoprotein of the avian tumor virus envelope. As measured by immune precipitation with a specific antiserum, gp85 does not accumulate to detectable levels in R(-)Q cells.", "contents": "Viral glycoprotein synthesis studies in an established line of Japanese quail embryo cells infected with the Bryan high-titer strain of Rous sarcoma virus. Although a glycoprotein with an approximate molecular weight of 43,000 is associated with purified virions of the Bryan high-titer strain of Rous sarcoma virus propagated on R(-)Q cells, these virions lack gp85, the major glycoprotein of the avian tumor virus envelope. As measured by immune precipitation with a specific antiserum, gp85 does not accumulate to detectable levels in R(-)Q cells."} {"id": "PMID:178893", "title": "Epstein-Barr virus-specific RNA. I. Analysis of viral RNA in cellular extracts and in the polyribosomal fraction of permissive and nonpermissive lymphoblastoid cell lines.", "content": "We analyzed the viral RNA in permissive and nonpermissive Epstein-Barr virus (EBV) Pinfected lymphoblastoid cell lines by observing the kinetics of hybridization of labeled EBV HR-1 DNA with unalabeled RNA extracted from whole cells or from the polyribosomal fraction. The data indicate the following. (i) RNA, homologous to only 3% of the EBV HR-1 DNA, is present in the polyribosomal fraction of the nonpermissive Namalwa and Kurgans cells, suggesting that the function of only a small fraction of the EBV genome is required for the expression of the EBV-related intranuclear antigen and to maintain lymphoblastoid cells in a transformed state. (ii) In general, the extent of the viral DNA sequences transcribed into stable RNA correlates with the extent of phenotypic expression of the EBV geonome. RNA extracted from virus-producing HR-1 cells contains RNA sequences transcribed from at least 45% of the viral DNA, whereas the nonpermissive cell lines contain transcripts homologous to a much smaller proportion of the EBV DNA. (iii) Viral RNA sequences found in the polyribosomal fraction of HR-1 cells arise from almost the same template as the viral RNA sequences in extracts of infractionated HR-1 cells. In contrast, in nonpermissive lymphoblastoid cells, less than 30% of the viral RNA species found in whole-cell extracts can be identified in the polyribosomal fraction. We interpret these observations to indicate that the expression of EBV genetic information is regulated in at least two ways: first, by some mechanism that regulates which DNA sequences give rise to stable RNA; second, through a mechanism whereby certain viral RBA transcripts are selectively excluded from stable association with the polyribosomes.", "contents": "Epstein-Barr virus-specific RNA. I. Analysis of viral RNA in cellular extracts and in the polyribosomal fraction of permissive and nonpermissive lymphoblastoid cell lines. We analyzed the viral RNA in permissive and nonpermissive Epstein-Barr virus (EBV) Pinfected lymphoblastoid cell lines by observing the kinetics of hybridization of labeled EBV HR-1 DNA with unalabeled RNA extracted from whole cells or from the polyribosomal fraction. The data indicate the following. (i) RNA, homologous to only 3% of the EBV HR-1 DNA, is present in the polyribosomal fraction of the nonpermissive Namalwa and Kurgans cells, suggesting that the function of only a small fraction of the EBV genome is required for the expression of the EBV-related intranuclear antigen and to maintain lymphoblastoid cells in a transformed state. (ii) In general, the extent of the viral DNA sequences transcribed into stable RNA correlates with the extent of phenotypic expression of the EBV geonome. RNA extracted from virus-producing HR-1 cells contains RNA sequences transcribed from at least 45% of the viral DNA, whereas the nonpermissive cell lines contain transcripts homologous to a much smaller proportion of the EBV DNA. (iii) Viral RNA sequences found in the polyribosomal fraction of HR-1 cells arise from almost the same template as the viral RNA sequences in extracts of infractionated HR-1 cells. In contrast, in nonpermissive lymphoblastoid cells, less than 30% of the viral RNA species found in whole-cell extracts can be identified in the polyribosomal fraction. We interpret these observations to indicate that the expression of EBV genetic information is regulated in at least two ways: first, by some mechanism that regulates which DNA sequences give rise to stable RNA; second, through a mechanism whereby certain viral RBA transcripts are selectively excluded from stable association with the polyribosomes."} {"id": "PMID:178894", "title": "Inhibition of pseudorabies virus replication by vesicular stomicles virus I. Activity of infectious and inactivated B particles.", "content": "Infectious B particles of vesicular stomatitis virus (VSV) are capable of inhibiting the replication of pseudorabies virus (PSR) in a variety of cell lines. Even under conditions of an abortive infection in a continuous line of rabbit cornea cells (RC-6O), B particles interfere with the replication of PSR with high efficiency. Particle per cell dose-response analysis of B particle populations revealed that the number of VSV particles capable of inhibiting PSR replication exceeds the number of PFU by a factor of 32 to 64. When B particles are treated with UV irradiation, a drastic increase in the multiplicity of infection is required to inhibit PSR replication. Whereas one infective B particles per cell is sufficient to prevent replication of PSR, 800 to 1,000 VSV particles rendered noninfective by UV irradiation are required to compensate for the loss of VSV synthetic activity that results from irradiation. Temperature-sensitive mutants representing five complementation groups of VSV were tested at low multiplicities of infection for their effect on PSR replication at the nonpermissive temperature. Generally, the ability of the different complementation groups to amplify virion products at the nonpermissive temperature is associated with their ability to inhibit PSR replication. These results imply that at low multiplicities of infection, amplification of infecting VSV components is necessary for inhibition of PSR replication., but at high multiplicities of infection with VSV, a virion component can prevent PSR replication in the absence of de novo VSV RNA or protein synthesis.", "contents": "Inhibition of pseudorabies virus replication by vesicular stomicles virus I. Activity of infectious and inactivated B particles. Infectious B particles of vesicular stomatitis virus (VSV) are capable of inhibiting the replication of pseudorabies virus (PSR) in a variety of cell lines. Even under conditions of an abortive infection in a continuous line of rabbit cornea cells (RC-6O), B particles interfere with the replication of PSR with high efficiency. Particle per cell dose-response analysis of B particle populations revealed that the number of VSV particles capable of inhibiting PSR replication exceeds the number of PFU by a factor of 32 to 64. When B particles are treated with UV irradiation, a drastic increase in the multiplicity of infection is required to inhibit PSR replication. Whereas one infective B particles per cell is sufficient to prevent replication of PSR, 800 to 1,000 VSV particles rendered noninfective by UV irradiation are required to compensate for the loss of VSV synthetic activity that results from irradiation. Temperature-sensitive mutants representing five complementation groups of VSV were tested at low multiplicities of infection for their effect on PSR replication at the nonpermissive temperature. Generally, the ability of the different complementation groups to amplify virion products at the nonpermissive temperature is associated with their ability to inhibit PSR replication. These results imply that at low multiplicities of infection, amplification of infecting VSV components is necessary for inhibition of PSR replication., but at high multiplicities of infection with VSV, a virion component can prevent PSR replication in the absence of de novo VSV RNA or protein synthesis."} {"id": "PMID:178895", "title": "Inhibition of pseudorabies virus replication by vesicular stomatitis virus. II Activity of defective interfering particles.", "content": "Purified defective interfering (DI) particles of vesicular stomatitis virus (VSV) inhibit the replication of a heterologous virus, pseudorabies virus (PSR), in hamster (BHK-21) and rabbit (RC-60) cell lines. In contrast to infectious B particles of VSV, UV irradiation of DI particles does not reduce their ability to inhibit PSR replication. However, UV irradiation progressively reduces the ability of DI particles to cause homologous interference with B particle replication. Pretreatment with interferon does not affect the ability of DI particles to inhibit PSR replication in a rabbit cell line (RC-60) in which RNA, but not DNA, viruses are sensitive to the action of interferon. Under similar conditions of interferon pretreatment, the inhibition of PSR by B particles is blocked. These data suggest that de novo VSV RNA or protein synthesis is not required for the inhibition of PSR replication by DI particles. DI particles that inhibit PSR replication also inhibit host RNA and protein synthesis in BHK-21 and RC-60 cells. Based on the results described and data in the literature, it is proposed that the same component of VSV B and DI particles is responsible for most, if not all, of the inhibitory activities of VSV, except homologous interference.", "contents": "Inhibition of pseudorabies virus replication by vesicular stomatitis virus. II Activity of defective interfering particles. Purified defective interfering (DI) particles of vesicular stomatitis virus (VSV) inhibit the replication of a heterologous virus, pseudorabies virus (PSR), in hamster (BHK-21) and rabbit (RC-60) cell lines. In contrast to infectious B particles of VSV, UV irradiation of DI particles does not reduce their ability to inhibit PSR replication. However, UV irradiation progressively reduces the ability of DI particles to cause homologous interference with B particle replication. Pretreatment with interferon does not affect the ability of DI particles to inhibit PSR replication in a rabbit cell line (RC-60) in which RNA, but not DNA, viruses are sensitive to the action of interferon. Under similar conditions of interferon pretreatment, the inhibition of PSR by B particles is blocked. These data suggest that de novo VSV RNA or protein synthesis is not required for the inhibition of PSR replication by DI particles. DI particles that inhibit PSR replication also inhibit host RNA and protein synthesis in BHK-21 and RC-60 cells. Based on the results described and data in the literature, it is proposed that the same component of VSV B and DI particles is responsible for most, if not all, of the inhibitory activities of VSV, except homologous interference."} {"id": "PMID:178896", "title": "Differential inhibition of host protein synthesis in L cells infected with RNA - temperature-sensitive mutants of vesicular stomatitis virus.", "content": "The response of mouse L cells to infection with wild-type (wt) and temperature-sensitive (ts) mutants of vesicular stomatitis virus was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to delineate the synthesis of host cell and viral proteins. Experiments utilized transcriptase mutants of complementation group I (ts114 and ts13), a group IV mutant (ts44) that is restricted in total RNA synthesis (RNA-1) but not in primary transcription, and a group II mutant (ts52) variably restricted in RNA synthesis (RNA +/-). L cells infected with ts mutants at permissive temperature exhibited the wt response of progressive inhibition of host cell protein synthesis accompanied by accumulation of all five viral proteins. Mutant ts44 (IV) also switched off cell protein synthesis at restrictive temperature and accumulated all five viral proteins, but with disproportionate ratios of N and G proteins. At restrictive temperature, cells infected with group I ts mutants failed to accumulate any viral protein and did not exhibit significant reduction in host cell protein synthesis. These data suggest that vesicular stomatitis virus inhibits cell protein synthesis at a stage of viral infection after transcription and possibly translation but preceding replication of progeny viral RNA.", "contents": "Differential inhibition of host protein synthesis in L cells infected with RNA - temperature-sensitive mutants of vesicular stomatitis virus. The response of mouse L cells to infection with wild-type (wt) and temperature-sensitive (ts) mutants of vesicular stomatitis virus was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to delineate the synthesis of host cell and viral proteins. Experiments utilized transcriptase mutants of complementation group I (ts114 and ts13), a group IV mutant (ts44) that is restricted in total RNA synthesis (RNA-1) but not in primary transcription, and a group II mutant (ts52) variably restricted in RNA synthesis (RNA +/-). L cells infected with ts mutants at permissive temperature exhibited the wt response of progressive inhibition of host cell protein synthesis accompanied by accumulation of all five viral proteins. Mutant ts44 (IV) also switched off cell protein synthesis at restrictive temperature and accumulated all five viral proteins, but with disproportionate ratios of N and G proteins. At restrictive temperature, cells infected with group I ts mutants failed to accumulate any viral protein and did not exhibit significant reduction in host cell protein synthesis. These data suggest that vesicular stomatitis virus inhibits cell protein synthesis at a stage of viral infection after transcription and possibly translation but preceding replication of progeny viral RNA."} {"id": "PMID:178897", "title": "Characterizatiion of rat genetic sequences of Kirsten sarcoma virus: distinct class of endogenous rat type C viral sequences.", "content": "The nucleic acid sequences found in DNA and RNA from rat cells which are homologous to Kirsten sarcoma virus have been characterized. The homologous sequences are present in multiple copies per diploid rat cellular genome in a variety of different rat cellular dna's. In certain cells that constitutively express only low levels of sequences homologous to Kirsten sarcoma virus, bromodeoxyuridine treatment leads to the expression of high levels of these sequences in RNA. Supernatants from cell lines producing the sequences homologous to Kirsten sarcoma virus contain high levels of these sequences which are purified to the same degree as the previously known rat type C viral nucleic acid sequences by type C particles being released from such cells. The results indicate that the sequences in rat cells homologous to Kisten sarcoma virus have three characteristics of known mammalian type C viruses, and suggest that at least part of Kirsten sarcoma virus rat-derived sequences represent a distinct class of endogenous rat type C virus that has no detectable homology to the other known class of endogenous rat type C virus.", "contents": "Characterizatiion of rat genetic sequences of Kirsten sarcoma virus: distinct class of endogenous rat type C viral sequences. The nucleic acid sequences found in DNA and RNA from rat cells which are homologous to Kirsten sarcoma virus have been characterized. The homologous sequences are present in multiple copies per diploid rat cellular genome in a variety of different rat cellular dna's. In certain cells that constitutively express only low levels of sequences homologous to Kirsten sarcoma virus, bromodeoxyuridine treatment leads to the expression of high levels of these sequences in RNA. Supernatants from cell lines producing the sequences homologous to Kirsten sarcoma virus contain high levels of these sequences which are purified to the same degree as the previously known rat type C viral nucleic acid sequences by type C particles being released from such cells. The results indicate that the sequences in rat cells homologous to Kisten sarcoma virus have three characteristics of known mammalian type C viruses, and suggest that at least part of Kirsten sarcoma virus rat-derived sequences represent a distinct class of endogenous rat type C virus that has no detectable homology to the other known class of endogenous rat type C virus."} {"id": "PMID:178898", "title": "Use of alkaline sucrose gradients in a zonal rotor to detect integrated and unintegrated avian sarcoma virus-specific DNA in cells.", "content": "We have attempted to distinguish integrated and unintegrated forms of avian sarcoma virus-specific DNA in cells by sedimentaton through an alkaline sucrose gradient in a slowly reorienting zonal rotor. Results obtained with this procedure are similar to those obtained by the more convenient analysis of networks of high-molecular-weight cell DNA. Most, if not all, viral DNA appears completely integrated into the host cell genome in an avian sarcoma virus-transformed mammalian cell and in normal chicken cells (in which viral DNA is genetically transmitted). Fully transformed duck cells and duck embryo fibroblasts infected for 20 to 72 h contain both integrated and unintegrated viral DNA; up to one copy per cell is integrated within 20 h after infection, and four to eight copies are integrated in fully transformed cells. The amount of unintegrated DNA varies but may comprise over 75% of the viral DNA in acutely infected cells and from 20 to 70% of the viral DNA in fully transformed cells. The unintegrated DNA in either case consists principally of duplexes with \"minus\" strands the length of a subunit of the viral genome (2.5 X 10(6) to 3 X 10(6) daltons) and relatively short \"plus\" strands (0.5 X 10(6) to 1.0 X 10(6) daltons).", "contents": "Use of alkaline sucrose gradients in a zonal rotor to detect integrated and unintegrated avian sarcoma virus-specific DNA in cells. We have attempted to distinguish integrated and unintegrated forms of avian sarcoma virus-specific DNA in cells by sedimentaton through an alkaline sucrose gradient in a slowly reorienting zonal rotor. Results obtained with this procedure are similar to those obtained by the more convenient analysis of networks of high-molecular-weight cell DNA. Most, if not all, viral DNA appears completely integrated into the host cell genome in an avian sarcoma virus-transformed mammalian cell and in normal chicken cells (in which viral DNA is genetically transmitted). Fully transformed duck cells and duck embryo fibroblasts infected for 20 to 72 h contain both integrated and unintegrated viral DNA; up to one copy per cell is integrated within 20 h after infection, and four to eight copies are integrated in fully transformed cells. The amount of unintegrated DNA varies but may comprise over 75% of the viral DNA in acutely infected cells and from 20 to 70% of the viral DNA in fully transformed cells. The unintegrated DNA in either case consists principally of duplexes with \"minus\" strands the length of a subunit of the viral genome (2.5 X 10(6) to 3 X 10(6) daltons) and relatively short \"plus\" strands (0.5 X 10(6) to 1.0 X 10(6) daltons)."} {"id": "PMID:178899", "title": "Evidence of methylation of B77 avian sarcoma virus genome RNA subunits.", "content": "B77 avian sarcoma virus RNA was labeled with (methyl-3H) methionine under conditions that prevent non-methyl incorporation of 3H radioactivity into purine rings. From the determined values for the extent of methylation of 4S RNA isolated from infected chicken embryo cells, it was estimated that 30 to 40S RNA subunits that results from heat denaturation of the 60 to 70S RNA contain approximately 21 methyl groups, of which 14 to 16 are present at internal positions as N6 -methyladenosine residues. In addition, each of the virion RNA subunits appears to contain about two methyl groups in the \"capped\" 5' -terminal structure m7G(5')ppp(5') gm. These properties are consistent with the hypothesis that the 30 to 40S genome RNA os oncornaviruses also serves an mRNA function in infected cells.", "contents": "Evidence of methylation of B77 avian sarcoma virus genome RNA subunits. B77 avian sarcoma virus RNA was labeled with (methyl-3H) methionine under conditions that prevent non-methyl incorporation of 3H radioactivity into purine rings. From the determined values for the extent of methylation of 4S RNA isolated from infected chicken embryo cells, it was estimated that 30 to 40S RNA subunits that results from heat denaturation of the 60 to 70S RNA contain approximately 21 methyl groups, of which 14 to 16 are present at internal positions as N6 -methyladenosine residues. In addition, each of the virion RNA subunits appears to contain about two methyl groups in the \"capped\" 5' -terminal structure m7G(5')ppp(5') gm. These properties are consistent with the hypothesis that the 30 to 40S genome RNA os oncornaviruses also serves an mRNA function in infected cells."} {"id": "PMID:178900", "title": "RNA- temperature-sensitive mutants of vesicular stomatitis virus: L-protein thermosensitivity accounts for transcriptase restriction of group I mutants.", "content": "In vitro transcriptase activity of three group I temperature-sensitive (ts) mutants of vesicular stomatitis virus restricted at 39 C was restored by L-protein fractions derived from wild-type (wt) vesicular stomatitis virion nucleo-capsids. Soluble NS protein from wt nucleocapsids did not reconstitute restricted transcriptions of the group I RNA-ts mutants. NS protein activity, but not L protein activity, was purified from the group I ts mutants; this NS fraction always displayed the wt phenotype in reconstitution assays. Neither the L nor the NS protein was capable of restoring the defective transcriptive activity of the group IV vesicular stomatitis virus mutant ts W16B.", "contents": "RNA- temperature-sensitive mutants of vesicular stomatitis virus: L-protein thermosensitivity accounts for transcriptase restriction of group I mutants. In vitro transcriptase activity of three group I temperature-sensitive (ts) mutants of vesicular stomatitis virus restricted at 39 C was restored by L-protein fractions derived from wild-type (wt) vesicular stomatitis virion nucleo-capsids. Soluble NS protein from wt nucleocapsids did not reconstitute restricted transcriptions of the group I RNA-ts mutants. NS protein activity, but not L protein activity, was purified from the group I ts mutants; this NS fraction always displayed the wt phenotype in reconstitution assays. Neither the L nor the NS protein was capable of restoring the defective transcriptive activity of the group IV vesicular stomatitis virus mutant ts W16B."} {"id": "PMID:178901", "title": "Effects of 2-deoxyglucose, glucosamine, and mannose on cell fusion and the glycoproteins of herpes simplex virus.", "content": "2-Deoxyglucose and glucosamine were found to inhibit cell fusion caused by a syncytial mutant of herpes simplex virus and to inhibit the glycosylation of viral glycoproteins in the infected cells. The inhibition of fusion and the inhibition of glycosylation caused by 2-deoxyglucose were substantially prevented when mannose was also present during infection. When glycosylation was inhibited, three new bands were found in major glycoprotein region on sodium dodecyl sulfate-polyacrylamide gels. These bands may be precursors to the normal glycoproteins. The correlation between fusion and glycosylation in the presence of 2-deoxyglucose, glucosamine, and mannose suggests that the cells cannot fuse if their glycoproteins have a considerably reduced carbohydrate content.", "contents": "Effects of 2-deoxyglucose, glucosamine, and mannose on cell fusion and the glycoproteins of herpes simplex virus. 2-Deoxyglucose and glucosamine were found to inhibit cell fusion caused by a syncytial mutant of herpes simplex virus and to inhibit the glycosylation of viral glycoproteins in the infected cells. The inhibition of fusion and the inhibition of glycosylation caused by 2-deoxyglucose were substantially prevented when mannose was also present during infection. When glycosylation was inhibited, three new bands were found in major glycoprotein region on sodium dodecyl sulfate-polyacrylamide gels. These bands may be precursors to the normal glycoproteins. The correlation between fusion and glycosylation in the presence of 2-deoxyglucose, glucosamine, and mannose suggests that the cells cannot fuse if their glycoproteins have a considerably reduced carbohydrate content."} {"id": "PMID:178902", "title": "Construction and analysis of viable deletion mutants of simian virus 40.", "content": "Viable mutants of simian virus 40 (SV40), with deletions ranging in size from 15 to 200 base pairs, have been obtained by infecting CV-1P cells with circularly permuted linear SV40 DNA. The linear DNA was produced by cleavage of closed circular DNA with DNase I in the presence of Mn2+, followed, in some cases, by mild digestion with lambda 5'-exonuclease. The SV40 map location and the size of each deletion were determined by using the S1 nuclease mapping procedure (Shenk et al., 1975) and the change in size of fragments produced by Hind II + III endonuclease cleavage. Deletions in at least three regions of the SV40 chromosome have slight or no effect on the rate or yield of viral multiplication and on vira-induced cellular transformation. These regions are located at the following coordinates on the SV40 physical map: 0.17 to 0.18; 0.54 to 0.59; and 0.68 to 0.74.", "contents": "Construction and analysis of viable deletion mutants of simian virus 40. Viable mutants of simian virus 40 (SV40), with deletions ranging in size from 15 to 200 base pairs, have been obtained by infecting CV-1P cells with circularly permuted linear SV40 DNA. The linear DNA was produced by cleavage of closed circular DNA with DNase I in the presence of Mn2+, followed, in some cases, by mild digestion with lambda 5'-exonuclease. The SV40 map location and the size of each deletion were determined by using the S1 nuclease mapping procedure (Shenk et al., 1975) and the change in size of fragments produced by Hind II + III endonuclease cleavage. Deletions in at least three regions of the SV40 chromosome have slight or no effect on the rate or yield of viral multiplication and on vira-induced cellular transformation. These regions are located at the following coordinates on the SV40 physical map: 0.17 to 0.18; 0.54 to 0.59; and 0.68 to 0.74."} {"id": "PMID:178903", "title": "Simian virus 40-specific polypeptides in AD2+ ND1- and Ad2+ ND4-infected cells.", "content": "A comparison of the proteins synthesized in human cells at late times after infection with adenovirus (Ad2) and with the adeno-simian virus 40 (SV40) hybrid viruses revealed polypeptides of 30,000 and 92,000 molecular weight specific for the hybrid viruses Ad2+ND1 and Ad2+ND4, respectively. Cell-free translation of SV40-specific mRNA, prepared from these cells by hybridization of total cytoplasmic RNA to SV40 DNA, showed that the mRNA's specifying these two polypeptides were at least partially encoded by the SV40 portion of the hybrid viruses. Cell-free translation of SV40-specific mRNA prepared from monkey cells infected with SV40 produced polypeptides of 40,000, 43,000, 48,500, and 92,000 molecular weight. The SV40 and Ad2+ND4 92,000-molecular-weight polypeptides made in vitro were very similar in electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels to the polypeptide precipitated by Tegtmeyer (1974) with SV40 anti-T serum.", "contents": "Simian virus 40-specific polypeptides in AD2+ ND1- and Ad2+ ND4-infected cells. A comparison of the proteins synthesized in human cells at late times after infection with adenovirus (Ad2) and with the adeno-simian virus 40 (SV40) hybrid viruses revealed polypeptides of 30,000 and 92,000 molecular weight specific for the hybrid viruses Ad2+ND1 and Ad2+ND4, respectively. Cell-free translation of SV40-specific mRNA, prepared from these cells by hybridization of total cytoplasmic RNA to SV40 DNA, showed that the mRNA's specifying these two polypeptides were at least partially encoded by the SV40 portion of the hybrid viruses. Cell-free translation of SV40-specific mRNA prepared from monkey cells infected with SV40 produced polypeptides of 40,000, 43,000, 48,500, and 92,000 molecular weight. The SV40 and Ad2+ND4 92,000-molecular-weight polypeptides made in vitro were very similar in electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels to the polypeptide precipitated by Tegtmeyer (1974) with SV40 anti-T serum."} {"id": "PMID:178904", "title": "Structural difference between the 5' termini of viral and cellular mRNA in poliovirus-infected cells: possible basis for the inhibition of host protein synthesis.", "content": "Host protein synthesis in poliovirus-infected HeLa cells is interrupted, but the host mRNA appears to remain completely intact and unmodified. The average size and poly (A) content of host mRNA was previously known to be unchanged (Koschel, 1974; Leibowitz and Penman, 1971), and this was confirmed. In addition, the 5' terminal methylated \"cap\" structures remained intact, and no further base modifications at the level of 1 base in 1,000 could be detected. Poliovirus RNA from viruses was previously shown not to have \"caps\" (Wimmer, 1972), and in this work poliovirus RNA from polyribosomes was found to have pUp at its 5' end. Since, initiation of protein synthesis is probably the basis for the inhibition of cellular protein synthesis in infected cells, the difference in the 5' ends of the host cell and viral RNA could be the basis of selective translation of viral RNA during infection.", "contents": "Structural difference between the 5' termini of viral and cellular mRNA in poliovirus-infected cells: possible basis for the inhibition of host protein synthesis. Host protein synthesis in poliovirus-infected HeLa cells is interrupted, but the host mRNA appears to remain completely intact and unmodified. The average size and poly (A) content of host mRNA was previously known to be unchanged (Koschel, 1974; Leibowitz and Penman, 1971), and this was confirmed. In addition, the 5' terminal methylated \"cap\" structures remained intact, and no further base modifications at the level of 1 base in 1,000 could be detected. Poliovirus RNA from viruses was previously shown not to have \"caps\" (Wimmer, 1972), and in this work poliovirus RNA from polyribosomes was found to have pUp at its 5' end. Since, initiation of protein synthesis is probably the basis for the inhibition of cellular protein synthesis in infected cells, the difference in the 5' ends of the host cell and viral RNA could be the basis of selective translation of viral RNA during infection."} {"id": "PMID:178905", "title": "Electron microscope studies of temperature-sensitive mutants of herpes simplex virus type 2.", "content": "Nine temperature-sensitive mutants of herpes simplex virus type 2 representing eight complementation groups were assigned to two classes as a consequence of the virion forms and virus-specific cellular alterations observed in thin sections of mutant-infected human embryonic lung cells grown at the nonpermissive temperature. Mutants in class A, one DNA- and one DNA +, failed to synthesize detectable virus particles. Mutants in class B, 4DNA- and 3DNA+, produced moderate to large numbers of empty nucleocapsids. Dense-cored nucleocapsids were not observed in thin sections of cells infected with any of the nine mutants at this temperature. Virus-specific cellular alterations consisted primarily of margination of chromating and nulcear membrane thickening and duplication.", "contents": "Electron microscope studies of temperature-sensitive mutants of herpes simplex virus type 2. Nine temperature-sensitive mutants of herpes simplex virus type 2 representing eight complementation groups were assigned to two classes as a consequence of the virion forms and virus-specific cellular alterations observed in thin sections of mutant-infected human embryonic lung cells grown at the nonpermissive temperature. Mutants in class A, one DNA- and one DNA +, failed to synthesize detectable virus particles. Mutants in class B, 4DNA- and 3DNA+, produced moderate to large numbers of empty nucleocapsids. Dense-cored nucleocapsids were not observed in thin sections of cells infected with any of the nine mutants at this temperature. Virus-specific cellular alterations consisted primarily of margination of chromating and nulcear membrane thickening and duplication."} {"id": "PMID:178906", "title": "Proteins of Yaba monkey tumor virus I. Structural proteins.", "content": "Yaba virus proteins were characterized by polyacrylamide gel electrophoresis. Electrophoresis of Yaba virion (proteins) dissociated by sodium dodecyl sulfate and 2-mercaptoethanol in continuous and discontinuous buffer systems yielded 37 polypeptide species by staining and by counting bands of radioactively labeled polypeptides. The molecular weights of the viral polypeptide species were found to range from 10,000 to 220,000 by comparing the relative distance of migration of viral proteins with proteins of known molecular weights. Two polypeptides were removed from purified virions by nonionic detergent nonidet P -40 treatment, and the amount of one polypeptide was reduced. Purified cores yielded 21 polypeptide species, none of which was labeled with radioactive glucosamine.", "contents": "Proteins of Yaba monkey tumor virus I. Structural proteins. Yaba virus proteins were characterized by polyacrylamide gel electrophoresis. Electrophoresis of Yaba virion (proteins) dissociated by sodium dodecyl sulfate and 2-mercaptoethanol in continuous and discontinuous buffer systems yielded 37 polypeptide species by staining and by counting bands of radioactively labeled polypeptides. The molecular weights of the viral polypeptide species were found to range from 10,000 to 220,000 by comparing the relative distance of migration of viral proteins with proteins of known molecular weights. Two polypeptides were removed from purified virions by nonionic detergent nonidet P -40 treatment, and the amount of one polypeptide was reduced. Purified cores yielded 21 polypeptide species, none of which was labeled with radioactive glucosamine."} {"id": "PMID:178907", "title": "Nucleic acid renaturation and restriction endonuclease cleavage analyses show that the DNAs of a transforming and a nontransforming strain of Epstein-Barr virus share approximately 90% of their nucleotide sequences.", "content": "Viral DNA molecules were purified from a nontransforming and a transforming strain of Epstein-Barr virus. Each viral DNA was labeled in vitro and renatured in the presence of an excess of either one or the other unlabeled viral DNA. Both viral DNAs were also digested with the Eco R1 restriction endonuclease and subsequently labeled by using avian myeloblastosis virus DNA polymerase to repair either the EcoR1 nuclease-generated single-stranded ends of the DNAs or their single-stranded ends produced by a second digestion with exonuclease III after the first EcoR1 nuclease digestion. The results of these experiments support three general conclusions: (i) the DNAs of these two strains of Epstein-Barr virus share approximately 90% of their nucleotide sequences; (ii) both viral DNA populations are reasonably homogenous; and (iii) both DNAs contain repetitions or inverted repetitions of some of their nucleotide sequences.", "contents": "Nucleic acid renaturation and restriction endonuclease cleavage analyses show that the DNAs of a transforming and a nontransforming strain of Epstein-Barr virus share approximately 90% of their nucleotide sequences. Viral DNA molecules were purified from a nontransforming and a transforming strain of Epstein-Barr virus. Each viral DNA was labeled in vitro and renatured in the presence of an excess of either one or the other unlabeled viral DNA. Both viral DNAs were also digested with the Eco R1 restriction endonuclease and subsequently labeled by using avian myeloblastosis virus DNA polymerase to repair either the EcoR1 nuclease-generated single-stranded ends of the DNAs or their single-stranded ends produced by a second digestion with exonuclease III after the first EcoR1 nuclease digestion. The results of these experiments support three general conclusions: (i) the DNAs of these two strains of Epstein-Barr virus share approximately 90% of their nucleotide sequences; (ii) both viral DNA populations are reasonably homogenous; and (iii) both DNAs contain repetitions or inverted repetitions of some of their nucleotide sequences."} {"id": "PMID:178908", "title": "Acceleration of transformation of rat embryo cells by rat type C virus.", "content": "Sprague-Dawley and Fischer rat embryo cells became spontaneously transformed about 20 passages after release of endogenous ecotropic type C virus (SD-RaLV and F-RaLV). The virus-producing transformed cells showed loss of contact inhibition, increased growth rate, and tumorigenicity in vivo. Exogenous infection of other Fischer rat embryo cultures in early passage with SD-RaLV and F-RaLV markedly accelerated their rates of transformation.", "contents": "Acceleration of transformation of rat embryo cells by rat type C virus. Sprague-Dawley and Fischer rat embryo cells became spontaneously transformed about 20 passages after release of endogenous ecotropic type C virus (SD-RaLV and F-RaLV). The virus-producing transformed cells showed loss of contact inhibition, increased growth rate, and tumorigenicity in vivo. Exogenous infection of other Fischer rat embryo cultures in early passage with SD-RaLV and F-RaLV markedly accelerated their rates of transformation."} {"id": "PMID:178909", "title": "Mechanism of premature polypetide termination in a mouse ascites cell-free system programmed by encephalomyocarditis viral RNA.", "content": "The premature termination and release of encephalomyocarditis viral RNA-programmed polypeptides were analyzed in a cell-free system from mouse ascites tumor cells. The KCL concentration affects the size distribution of products but not the extent of polypeptide release. The same major products (60,000 to 140,000 molecular weight) are found in both the soluble and particulate fractions. The majority of released polypeptides are free protein, whereas the ribosome-bound product is mostly in the form of peptidyl-tRNA.", "contents": "Mechanism of premature polypetide termination in a mouse ascites cell-free system programmed by encephalomyocarditis viral RNA. The premature termination and release of encephalomyocarditis viral RNA-programmed polypeptides were analyzed in a cell-free system from mouse ascites tumor cells. The KCL concentration affects the size distribution of products but not the extent of polypeptide release. The same major products (60,000 to 140,000 molecular weight) are found in both the soluble and particulate fractions. The majority of released polypeptides are free protein, whereas the ribosome-bound product is mostly in the form of peptidyl-tRNA."} {"id": "PMID:178910", "title": "Restriction endonuclease from Haemophilus gallinarum (HgaI) cleaves polyoma DNA at four locations.", "content": "A restriction endonuclease obtained from Haemophilus gallinarum (hgaI) cleaves polyoma DNA at four specific sites. Using the EcoRI, HindIII, and HpaII endonuclease restriction sites as reference, the four HgaI cleavage sites were mapped at 0.02, 0.14, 0.27, and 0.48 fractional lengths, clockwise, from the single EcoRI cleavage site.", "contents": "Restriction endonuclease from Haemophilus gallinarum (HgaI) cleaves polyoma DNA at four locations. A restriction endonuclease obtained from Haemophilus gallinarum (hgaI) cleaves polyoma DNA at four specific sites. Using the EcoRI, HindIII, and HpaII endonuclease restriction sites as reference, the four HgaI cleavage sites were mapped at 0.02, 0.14, 0.27, and 0.48 fractional lengths, clockwise, from the single EcoRI cleavage site."} {"id": "PMID:178911", "title": "Sialylatin of glycoproteins of murine mammary tumor virus, murine leukemia virus, and Mason-Pfizer monkey virus.", "content": "Neuraminidase treatment of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus resulted in loss of their capacity to inhibit hemagglutination of influenza virus. Hemagglutination-inhibition activity of these RNA tumor viruses could be restored by in vitro resialylation catalyzed by sialyl transferase. The major glycoprotein in the intact envelope of desialylated and, to some extent, native virions could be specificallly labeled in vitro with CMP-(14C) sialic acid. These studies further characterize the individual glycoproteins of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus.", "contents": "Sialylatin of glycoproteins of murine mammary tumor virus, murine leukemia virus, and Mason-Pfizer monkey virus. Neuraminidase treatment of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus resulted in loss of their capacity to inhibit hemagglutination of influenza virus. Hemagglutination-inhibition activity of these RNA tumor viruses could be restored by in vitro resialylation catalyzed by sialyl transferase. The major glycoprotein in the intact envelope of desialylated and, to some extent, native virions could be specificallly labeled in vitro with CMP-(14C) sialic acid. These studies further characterize the individual glycoproteins of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus."} {"id": "PMID:178912", "title": "Replication of human cytomegalovirus DNA: lack of dependence on cell DNA synthesis.", "content": "Human cytomegalovirus (CMV) DNA synthesis was studied in 5-fluorouracil (FU)-treated and untreated human embryonic lung cells, which differ greatly with respect to the number of cells in the culture synthesizing cellular DNA. CMV DNA synthesis proceeded at the same rate in FU-treated and in untreated cells. CMV infection also reversed the inhibitory effects of FU and activated cellular DNA synthesis in some of the cells in the FU-treated culture. Autoradiographic studies showed that more than 20% of the cells in the infected FU-treated culture synthesized viral DNA when less than 1% had synthesized cellular DNA, indicating that the synthesis of viral macromolecules proceeds in cells that do not synthesize cellular DNA from the time of infection, and that viral DNA synthesis proceeds independently of the host cell DNA synthesis. Combined autoradiographic and immunofluorescence studies of both the FU-treated and untreated infected cells showed that, whereas 20% of the cells in the cultures synthesize viral DNA and viral antigens, only about 3 to 6% of those cells that synthesize cellular DNA also synthesize viral antigen. Thus, productive infection was delayed or inhibited in those cells that were stimulated by CMV infection to synthesize cellular DNA.", "contents": "Replication of human cytomegalovirus DNA: lack of dependence on cell DNA synthesis. Human cytomegalovirus (CMV) DNA synthesis was studied in 5-fluorouracil (FU)-treated and untreated human embryonic lung cells, which differ greatly with respect to the number of cells in the culture synthesizing cellular DNA. CMV DNA synthesis proceeded at the same rate in FU-treated and in untreated cells. CMV infection also reversed the inhibitory effects of FU and activated cellular DNA synthesis in some of the cells in the FU-treated culture. Autoradiographic studies showed that more than 20% of the cells in the infected FU-treated culture synthesized viral DNA when less than 1% had synthesized cellular DNA, indicating that the synthesis of viral macromolecules proceeds in cells that do not synthesize cellular DNA from the time of infection, and that viral DNA synthesis proceeds independently of the host cell DNA synthesis. Combined autoradiographic and immunofluorescence studies of both the FU-treated and untreated infected cells showed that, whereas 20% of the cells in the cultures synthesize viral DNA and viral antigens, only about 3 to 6% of those cells that synthesize cellular DNA also synthesize viral antigen. Thus, productive infection was delayed or inhibited in those cells that were stimulated by CMV infection to synthesize cellular DNA."} {"id": "PMID:178913", "title": "Biological properties and viral surface antigens of Burkitt lymphoma- and mononucleosis- derived strains of Epstein-Barr virus released from transformed marmoset cells.", "content": "Three strains of Epstein-Barr virus (EBV), two from Burkitt lymphoma (BL) and one from infectious mononucleosis (IM) were used to transform separate cultures of the same batch of primary marmoset leukocytes, and the viruses released from the transformants were compared. The three viruses shared properties of the transforming biotype of EBV, namely, stimulation of DNA synthesis and immortalization of cord blood leukocytes, and failure to induce \"early antigen\" in lymphoblast lines. All viruses produced more virus in transformed marmoset cells than in transformed human cells, as measured by the number of EBV genomes detected by complementary RNA/DNA hybridization, by virus capsid antigen expression, or by released virions and biologically active virus. Reference human sera and sera from primary EBV infections were used to compare the three virus strains in a virus neutralization test based on inhibition of stimulation of DNA synthesis. Specimens taken late in convalescence from patients with mononucleosis and sera from marmosets experimentally infected with virus from a patient with mononucleosis neutralized the homologous virus, as well as the two virus strains isolated from patients with BL. This finding indicates that viral antigens that elicit neutralizing antibodies are shared among the strains. However, in certain sera the neutralizing-antibody titer against one strain was consistently higher than against another strain. Furthermore, sera taken early after onset of IM contained low levels of neutralizing antibody against IM-derived virus, but failed to neutralize BL-derived virus. These latter findings suggest the existence of heterogeneity among surface antigens of EBVs. The results emphasize the biological and antigenic similarity of EBV isolates from BL and IM and do not suggest major subtype variations. It remains to be determined whether antigenic diversity such as described or virus genome variation detectable by other means is epidemiologically significant.", "contents": "Biological properties and viral surface antigens of Burkitt lymphoma- and mononucleosis- derived strains of Epstein-Barr virus released from transformed marmoset cells. Three strains of Epstein-Barr virus (EBV), two from Burkitt lymphoma (BL) and one from infectious mononucleosis (IM) were used to transform separate cultures of the same batch of primary marmoset leukocytes, and the viruses released from the transformants were compared. The three viruses shared properties of the transforming biotype of EBV, namely, stimulation of DNA synthesis and immortalization of cord blood leukocytes, and failure to induce \"early antigen\" in lymphoblast lines. All viruses produced more virus in transformed marmoset cells than in transformed human cells, as measured by the number of EBV genomes detected by complementary RNA/DNA hybridization, by virus capsid antigen expression, or by released virions and biologically active virus. Reference human sera and sera from primary EBV infections were used to compare the three virus strains in a virus neutralization test based on inhibition of stimulation of DNA synthesis. Specimens taken late in convalescence from patients with mononucleosis and sera from marmosets experimentally infected with virus from a patient with mononucleosis neutralized the homologous virus, as well as the two virus strains isolated from patients with BL. This finding indicates that viral antigens that elicit neutralizing antibodies are shared among the strains. However, in certain sera the neutralizing-antibody titer against one strain was consistently higher than against another strain. Furthermore, sera taken early after onset of IM contained low levels of neutralizing antibody against IM-derived virus, but failed to neutralize BL-derived virus. These latter findings suggest the existence of heterogeneity among surface antigens of EBVs. The results emphasize the biological and antigenic similarity of EBV isolates from BL and IM and do not suggest major subtype variations. It remains to be determined whether antigenic diversity such as described or virus genome variation detectable by other means is epidemiologically significant."} {"id": "PMID:178914", "title": "Preliminary biochemical characterization of the factors(s) responsible for herpesvirus-induced exogenous fusion.", "content": "Cell-free extracts prepared from herpes simplex virus-infected BHK-21 cells rapidly induced exogenous fusion when incubated with indicator monolayers of uninfected BHK-21 cells. Fusion was first observed at 1 h, and peak activity was reached by 4 h. Divalent cations were required for activity. Inhibition of indicator cell macromolecular synthesis, with metabolic inhibitors, failed to prevent formation of cell-free extract-induced polykaryocytes. Removal of virus particles from the cell-free extract by velocity sedimentation centrifugation did not affect cell-free extract exogenous fusion activity. Studies using molecular probes, namely, glycosidases, lectins, and antiserum (directed against either HSV envelope or capsid proteins), suggest that the factor(s) responsible for herpesvirus fusion is a fucosylated glycoprotein that is not a structural component of the virion.", "contents": "Preliminary biochemical characterization of the factors(s) responsible for herpesvirus-induced exogenous fusion. Cell-free extracts prepared from herpes simplex virus-infected BHK-21 cells rapidly induced exogenous fusion when incubated with indicator monolayers of uninfected BHK-21 cells. Fusion was first observed at 1 h, and peak activity was reached by 4 h. Divalent cations were required for activity. Inhibition of indicator cell macromolecular synthesis, with metabolic inhibitors, failed to prevent formation of cell-free extract-induced polykaryocytes. Removal of virus particles from the cell-free extract by velocity sedimentation centrifugation did not affect cell-free extract exogenous fusion activity. Studies using molecular probes, namely, glycosidases, lectins, and antiserum (directed against either HSV envelope or capsid proteins), suggest that the factor(s) responsible for herpesvirus fusion is a fucosylated glycoprotein that is not a structural component of the virion."} {"id": "PMID:178915", "title": "In vitro synthesis of A-particle structual protein by membrane-bound polyribosomes.", "content": "On the basis of association with endoplasmic reticulum membranes, poyribosomes isolated from mouse myeloma MOPC-104E were separated into two classes, membrane bound and free. The membrane-bound and free polyribosomes were then compared for their capacity to incorporate [35S]methionine into A-particle proteins in vitro. As revealed by a radioimmunological assay method, labeling of A-particle protein occurred with the membrane-bound polyribosomes but not with the free polyribosomes. Peptide mapping of the immunoprecipitated, in vitro [35S]methionine-labeled product confirmed that A-particle protein had been synthesized in vitro.", "contents": "In vitro synthesis of A-particle structual protein by membrane-bound polyribosomes. On the basis of association with endoplasmic reticulum membranes, poyribosomes isolated from mouse myeloma MOPC-104E were separated into two classes, membrane bound and free. The membrane-bound and free polyribosomes were then compared for their capacity to incorporate [35S]methionine into A-particle proteins in vitro. As revealed by a radioimmunological assay method, labeling of A-particle protein occurred with the membrane-bound polyribosomes but not with the free polyribosomes. Peptide mapping of the immunoprecipitated, in vitro [35S]methionine-labeled product confirmed that A-particle protein had been synthesized in vitro."} {"id": "PMID:178916", "title": "Analysis of cytomegalovirus genomes with restriction endonucleases Hin D III and EcoR-1.", "content": "Cleavage of genomes of eleven human, one simian, and one simian-related cytomegalovirus (CMV) isolate by the restriction endonucleases HinD III and EcoR-1 generated reproducible DNA fragments. The size range of CMV DNA fragments as estimated by contour length measurements in comparison with simian virus 40 form II DNA and by coelectrophoresis with EcoR-1 fragments of herpes simplex virus DNA varied between 15 X 10(6) and 0.5 X 10(6) daltons. Comparison of the cleavage products of each isolate in 1% agarose slab gels showed extensive comigration of fragments among the human CMV isolates. In the HinD III digests, three fragment bands comigrated among all human CMV isolates, and six fragments comigrated among most, but not all, human CMV isolates. In the EcoR-1 digests, nine fragment bands comigrated among all human CMV isolates, and five bands comigrated among most, but not all human isolates. Each isolate had a distinctive electrophoretic profile with either HinD III or EcoR-1 digests. No two isolates had identical HinD III or EcoR-1 patterns although some isolates did share more general pattern similarities than others. No clear-cut subgrouping of isolates based on cleavage pattern characteristics could be discerned. Comparison of HinD III and EcoR-1 patterns showed that human isolates differ greatly from nonhuman CMV isolates. HinD III and EcoR-1 digests of each isolate contained both major and minor molar classes of DNA fragments that ranged from about 1 and multiples of 1 M down to about 0.25 M; however, the summed molecular weights for major molar fragments resulting from HinD III or EcoR-1 digests of several isolates closely approximated the molecular weight of 10(8) of the intact genome.", "contents": "Analysis of cytomegalovirus genomes with restriction endonucleases Hin D III and EcoR-1. Cleavage of genomes of eleven human, one simian, and one simian-related cytomegalovirus (CMV) isolate by the restriction endonucleases HinD III and EcoR-1 generated reproducible DNA fragments. The size range of CMV DNA fragments as estimated by contour length measurements in comparison with simian virus 40 form II DNA and by coelectrophoresis with EcoR-1 fragments of herpes simplex virus DNA varied between 15 X 10(6) and 0.5 X 10(6) daltons. Comparison of the cleavage products of each isolate in 1% agarose slab gels showed extensive comigration of fragments among the human CMV isolates. In the HinD III digests, three fragment bands comigrated among all human CMV isolates, and six fragments comigrated among most, but not all, human CMV isolates. In the EcoR-1 digests, nine fragment bands comigrated among all human CMV isolates, and five bands comigrated among most, but not all human isolates. Each isolate had a distinctive electrophoretic profile with either HinD III or EcoR-1 digests. No two isolates had identical HinD III or EcoR-1 patterns although some isolates did share more general pattern similarities than others. No clear-cut subgrouping of isolates based on cleavage pattern characteristics could be discerned. Comparison of HinD III and EcoR-1 patterns showed that human isolates differ greatly from nonhuman CMV isolates. HinD III and EcoR-1 digests of each isolate contained both major and minor molar classes of DNA fragments that ranged from about 1 and multiples of 1 M down to about 0.25 M; however, the summed molecular weights for major molar fragments resulting from HinD III or EcoR-1 digests of several isolates closely approximated the molecular weight of 10(8) of the intact genome."} {"id": "PMID:178917", "title": "Characterization of simian cells tranformed by temperature-sensitive mutants of simian virus 40.", "content": "Seven lines derived from primary African green monkey kidney cells, which had survived lytic infection by wild-type simian virus 40 (SV40) or temperature-sensitive mutants belonging to the A and B complementation groups, were established. These cultures synthesize SV40 tumor (T) antigen constitutively and have been passaged more than 60 times in vitro. The cells released small amounts of virus even at high passage levels but eventually became negative for the spontaneous release of virus. Virus rescued from such \"nonproducer\" cells by the transfection technique exhibited the growth properties of the original inoculum virus. Four of the cell lines were tested for the presence of altered growth patterns commonly associated with SV40-induced transformation. Although each of the cell lines was greater than 99% positive for T antigen, none of the cultures could be distinguished from primary or stable lines of normal simian cells on the basis of morphology, saturation density in high or low serum concentrations, colony formation on plastic or in soft agar, hexose transport, or concanavalin A agglutinability. However, the cells could be distinguished from the parental green monkey kidney cells by a prolonged life span, the presence of T antigen, a resistance to the replication of superinfecting SV40 virus or SV40 viral DNA, and, with three of the four lines, an ability to complement the growth of human adenovirus type 7. These properties were expressed independent of the temperature of incubation. These results indicate that the presence of an immunologically reactive SV40 T antigen is not sufficient to ensure induction of phenotypic transformation and suggest that a specific interaction between viral and cellular genes and/or gene products may be a necessary requirement.", "contents": "Characterization of simian cells tranformed by temperature-sensitive mutants of simian virus 40. Seven lines derived from primary African green monkey kidney cells, which had survived lytic infection by wild-type simian virus 40 (SV40) or temperature-sensitive mutants belonging to the A and B complementation groups, were established. These cultures synthesize SV40 tumor (T) antigen constitutively and have been passaged more than 60 times in vitro. The cells released small amounts of virus even at high passage levels but eventually became negative for the spontaneous release of virus. Virus rescued from such \"nonproducer\" cells by the transfection technique exhibited the growth properties of the original inoculum virus. Four of the cell lines were tested for the presence of altered growth patterns commonly associated with SV40-induced transformation. Although each of the cell lines was greater than 99% positive for T antigen, none of the cultures could be distinguished from primary or stable lines of normal simian cells on the basis of morphology, saturation density in high or low serum concentrations, colony formation on plastic or in soft agar, hexose transport, or concanavalin A agglutinability. However, the cells could be distinguished from the parental green monkey kidney cells by a prolonged life span, the presence of T antigen, a resistance to the replication of superinfecting SV40 virus or SV40 viral DNA, and, with three of the four lines, an ability to complement the growth of human adenovirus type 7. These properties were expressed independent of the temperature of incubation. These results indicate that the presence of an immunologically reactive SV40 T antigen is not sufficient to ensure induction of phenotypic transformation and suggest that a specific interaction between viral and cellular genes and/or gene products may be a necessary requirement."} {"id": "PMID:178918", "title": "Leukemia virus infection of mammalian cells: effect on two \"transformation-associated\" surface properties.", "content": "We demonstrated that the productive infection of three different mammalian cell lines with two separate leukemia viruses is sufficient to induce a change in surface architecture that may be detected as enhanced agglutinability with two different plant lectins. Subsequent transformation of one of these cell lines with a chemical carcinogen did not further modify the agglutinability of the cell lines. Using a polyoma virus-transformed derivative of one of the parental lines, we have demonstrated that the LETS protein (whose absence from the surface membrane has been considered a marker of the transformed phenotype) may be present in cells displaying the capacity to plate in soft agar.", "contents": "Leukemia virus infection of mammalian cells: effect on two \"transformation-associated\" surface properties. We demonstrated that the productive infection of three different mammalian cell lines with two separate leukemia viruses is sufficient to induce a change in surface architecture that may be detected as enhanced agglutinability with two different plant lectins. Subsequent transformation of one of these cell lines with a chemical carcinogen did not further modify the agglutinability of the cell lines. Using a polyoma virus-transformed derivative of one of the parental lines, we have demonstrated that the LETS protein (whose absence from the surface membrane has been considered a marker of the transformed phenotype) may be present in cells displaying the capacity to plate in soft agar."} {"id": "PMID:178919", "title": "Collaborative study of temperature-sensitive mutants of herpes simplex virus type 2.", "content": "Eighteen complementation groups were identified by complementation tests and by phenotype from twenty temperature-sensitive mutants isolated independently in Glasgow, Scotland, and Houston, Tex.", "contents": "Collaborative study of temperature-sensitive mutants of herpes simplex virus type 2. Eighteen complementation groups were identified by complementation tests and by phenotype from twenty temperature-sensitive mutants isolated independently in Glasgow, Scotland, and Houston, Tex."} {"id": "PMID:178920", "title": "Production of B-tropic murine leukemia virus by somatic cell hybrids between mouse peritoneal macrophages and simian virus 40-transformed human cells.", "content": "Simian virus 40 (SV40)-transformed human cells (LN-SV) were fused with BALB/c peritoneal macrophages (BALB/c X LN-SV) and with C57BL peritoneal macrophages (C57BL X LN-SV) and hybrid clones, all of which had segregated human chromosomes and contained the entire complement of mouse chromosomes, were isolated. All 15 BALB/c X LN-SV hybrid clones were producing varying titers (10 to 10(6) plaque-forming units/ml) of B-tropic murine leukemia virus, whereas none of the nine C57BL X LN-SV hybrid clones was producing detectable ecotropic murine leukemia virus.", "contents": "Production of B-tropic murine leukemia virus by somatic cell hybrids between mouse peritoneal macrophages and simian virus 40-transformed human cells. Simian virus 40 (SV40)-transformed human cells (LN-SV) were fused with BALB/c peritoneal macrophages (BALB/c X LN-SV) and with C57BL peritoneal macrophages (C57BL X LN-SV) and hybrid clones, all of which had segregated human chromosomes and contained the entire complement of mouse chromosomes, were isolated. All 15 BALB/c X LN-SV hybrid clones were producing varying titers (10 to 10(6) plaque-forming units/ml) of B-tropic murine leukemia virus, whereas none of the nine C57BL X LN-SV hybrid clones was producing detectable ecotropic murine leukemia virus."} {"id": "PMID:178921", "title": "Trypsin action on the growth of Sendai virus in tissue culture cells. IV. Evidence for activation of sendai virus by cleavage of a glycoprotein.", "content": "Results obtained by using a reconstitution technique on the Sendai virus envelope confirm that cleavage of one of the envelope glycoproteins (GP2) is prerequisite for activation of hemolytic and cell fusion activities of Sendai virus. The cleavage of GP2 occurs even when free envelope subunits are directly treated with trypsin in the presence of detergent. Trypsin treatment, either of the reconstituted particle or of the free envelope subunits but not of the intact virion, also causes a cleavage of the largest envelope glycoprotein (GP1), suggesting that a site on GP1 sensitive to trypsin becomes exposed during solubilization and reconstitution. The latter cleavage, however, is not associated with any changes in biological activities.", "contents": "Trypsin action on the growth of Sendai virus in tissue culture cells. IV. Evidence for activation of sendai virus by cleavage of a glycoprotein. Results obtained by using a reconstitution technique on the Sendai virus envelope confirm that cleavage of one of the envelope glycoproteins (GP2) is prerequisite for activation of hemolytic and cell fusion activities of Sendai virus. The cleavage of GP2 occurs even when free envelope subunits are directly treated with trypsin in the presence of detergent. Trypsin treatment, either of the reconstituted particle or of the free envelope subunits but not of the intact virion, also causes a cleavage of the largest envelope glycoprotein (GP1), suggesting that a site on GP1 sensitive to trypsin becomes exposed during solubilization and reconstitution. The latter cleavage, however, is not associated with any changes in biological activities."} {"id": "PMID:178922", "title": "Enterovirus type 70 virion and intracellular proteins.", "content": "The proteins of purified enterovirus type 70 grown in rhabdomyosarcoma cells and the intracellular proteins at 4 to 5 h after infection have been examined by polyacrylamide gel electrophoresis. Virions contained four proteins: P-1 (35,000, daltons) P-2 (28,000, daltons) P-3 (27,000, daltons) and P-4 (9,000 daltons). Further, addition of ZnCl2 to infected cultures inhibited virus plaque development and interfered with post-translational cleavage.", "contents": "Enterovirus type 70 virion and intracellular proteins. The proteins of purified enterovirus type 70 grown in rhabdomyosarcoma cells and the intracellular proteins at 4 to 5 h after infection have been examined by polyacrylamide gel electrophoresis. Virions contained four proteins: P-1 (35,000, daltons) P-2 (28,000, daltons) P-3 (27,000, daltons) and P-4 (9,000 daltons). Further, addition of ZnCl2 to infected cultures inhibited virus plaque development and interfered with post-translational cleavage."} {"id": "PMID:178923", "title": "Fluorosugars inhibit biological properties of different enveloped viruses.", "content": "Both 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose were found to be potent inhibitors of the synthesis of infectious Semliki forest and fowl plague virus in chicken embryo cells and also of pseudorabies virus grown in rabbit kidney cells. It was found that the pseudorabies virus-mediated cell fusion and the synthesis of functional hemagglutinin of fowl plague virus were blocked. In all cases the 2-deoxy-2-fluoro-D-mannose-caused inhibition was stronger than the 2-deoxy-2-fluoro-D-glucose- or 2-deoxy-D-glucose-mediated blocks. Studies on the virus-specified proteins from Semiliki forest virus-infected cells grown in the presence of the inhibitors show that the target of the fluorosugar action, parallel to the well-studied effects of 2-deoxy-D-glucose, is the glycoprotein biosynthesis.", "contents": "Fluorosugars inhibit biological properties of different enveloped viruses. Both 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose were found to be potent inhibitors of the synthesis of infectious Semliki forest and fowl plague virus in chicken embryo cells and also of pseudorabies virus grown in rabbit kidney cells. It was found that the pseudorabies virus-mediated cell fusion and the synthesis of functional hemagglutinin of fowl plague virus were blocked. In all cases the 2-deoxy-2-fluoro-D-mannose-caused inhibition was stronger than the 2-deoxy-2-fluoro-D-glucose- or 2-deoxy-D-glucose-mediated blocks. Studies on the virus-specified proteins from Semiliki forest virus-infected cells grown in the presence of the inhibitors show that the target of the fluorosugar action, parallel to the well-studied effects of 2-deoxy-D-glucose, is the glycoprotein biosynthesis."} {"id": "PMID:178924", "title": "Construction of the genetic map of the polyoma genome.", "content": "Seven early mutants, three late mutants, and one plaque morphology mutant of polyoma have been mapped by marker rescue using wild-type restriction endonuclease fragments. The early mutants map between 1.0 and 26.4 units from the Eco RI site, a region previously shown to correspond to the 3'-OH termainal half of \"early\" RNA (Kamen et al., 1974). The late mutants as well as the plaque morphology mutant map between 26.6 and 45.4 map units, a region previously shown to correspond to the 3'-OH terminal half of \"late\" RNA (Kamen et al., 1974). Analysis of the genotype of rescued virus demonstrated that the modification of the mutant DNA during marker rescue was limited to the region of the genome covered by the wild-type restriction endonuclease fragment tested.", "contents": "Construction of the genetic map of the polyoma genome. Seven early mutants, three late mutants, and one plaque morphology mutant of polyoma have been mapped by marker rescue using wild-type restriction endonuclease fragments. The early mutants map between 1.0 and 26.4 units from the Eco RI site, a region previously shown to correspond to the 3'-OH termainal half of \"early\" RNA (Kamen et al., 1974). The late mutants as well as the plaque morphology mutant map between 26.6 and 45.4 map units, a region previously shown to correspond to the 3'-OH terminal half of \"late\" RNA (Kamen et al., 1974). Analysis of the genotype of rescued virus demonstrated that the modification of the mutant DNA during marker rescue was limited to the region of the genome covered by the wild-type restriction endonuclease fragment tested."} {"id": "PMID:178925", "title": "RNA composition of Junin virus.", "content": "Junin virus grown in BHK-21 cells was labeled with [3H]uridine and highly purified by differential and isopycnic centrifugation. The RNAs extracted with phenol and analyzed by polyacrylamide gel electrophoresis were shown to be composed of four large species (33, 28, and 18S) and three small ones (4, 5, and 5.5S). This pattern was similar to ones already reported for other arenaviruses. However, there was a striking difference when the virus labeling was performed in the presence of actinomycin D. Labeling of viral rRNA was as much as 60% of the levels obtained in the absence of the drug under conditions in which cellular rRNA's were inhibited by 95% or more.", "contents": "RNA composition of Junin virus. Junin virus grown in BHK-21 cells was labeled with [3H]uridine and highly purified by differential and isopycnic centrifugation. The RNAs extracted with phenol and analyzed by polyacrylamide gel electrophoresis were shown to be composed of four large species (33, 28, and 18S) and three small ones (4, 5, and 5.5S). This pattern was similar to ones already reported for other arenaviruses. However, there was a striking difference when the virus labeling was performed in the presence of actinomycin D. Labeling of viral rRNA was as much as 60% of the levels obtained in the absence of the drug under conditions in which cellular rRNA's were inhibited by 95% or more."} {"id": "PMID:178926", "title": "Mutant of herpes simplex virus type 1 conditionally able to transform thymidine kinaseless L cells to a tk+ phenotype.", "content": "After nitrous acid mutagenesis of herpes simplex virus type 1 (HSV-1), a mutant, 1093, was isolated which, during productive infection, induced very low levels of thymidine kinase (tk). The mutant virus was found, after UV irradiation, to be unable to transform L cells lacking tk (Ltk-) to a tk+ phenotype as chararcterized by growth of the cells in a modified HAT-selective medium containing 1.6 X 10(-5) M thymidine. Cells transformed by wild-type virus grew vigorously under the same conditions. The mutant was able to transform Ltk- cells if the medium contained 10(-3) M thymidine. These transformed cells maintained their conditional character and would not grow in low concentrations of thymidine in selective medium. Therefore, this mutant is conditional on the thymidine concentration in the selection medium in its ability to transform Ltk- cells to a tk+ phenotype. The conditionally transformed cells could be supertransformed with wild-type UV-irradiated HSV-1 to a phenotype which would grow in low-thymidine selective medium. The frequency of supertransformation closely approximated the frequency of transformation of Ltk- cells by wild-type virus. Supertransformation at high frequency could not be effected by mutant 1093 or the tk- mutant B2006. These results indicate that the presence of HSV-1 genetic information in HSV-1-transformed cells does not preclude the acquisition by these cells of at least one additional HSV-1 gene, that for tk.", "contents": "Mutant of herpes simplex virus type 1 conditionally able to transform thymidine kinaseless L cells to a tk+ phenotype. After nitrous acid mutagenesis of herpes simplex virus type 1 (HSV-1), a mutant, 1093, was isolated which, during productive infection, induced very low levels of thymidine kinase (tk). The mutant virus was found, after UV irradiation, to be unable to transform L cells lacking tk (Ltk-) to a tk+ phenotype as chararcterized by growth of the cells in a modified HAT-selective medium containing 1.6 X 10(-5) M thymidine. Cells transformed by wild-type virus grew vigorously under the same conditions. The mutant was able to transform Ltk- cells if the medium contained 10(-3) M thymidine. These transformed cells maintained their conditional character and would not grow in low concentrations of thymidine in selective medium. Therefore, this mutant is conditional on the thymidine concentration in the selection medium in its ability to transform Ltk- cells to a tk+ phenotype. The conditionally transformed cells could be supertransformed with wild-type UV-irradiated HSV-1 to a phenotype which would grow in low-thymidine selective medium. The frequency of supertransformation closely approximated the frequency of transformation of Ltk- cells by wild-type virus. Supertransformation at high frequency could not be effected by mutant 1093 or the tk- mutant B2006. These results indicate that the presence of HSV-1 genetic information in HSV-1-transformed cells does not preclude the acquisition by these cells of at least one additional HSV-1 gene, that for tk."} {"id": "PMID:178927", "title": "Herpes simplex virus DNA in transformed cells: sequence complexity in five hamster cell lines and one derived hamster tumor.", "content": "Analyses of the hybridization kinetics of labeled herpes simplex virus 2 (HSV-2) DNA with DNA from five hamster cell lines transformed by UV light-irradiated HSV-2 revealed the following. (i) Viral DNA sequences were detected in all five cell lines tested. (ii) None of the cell lines contained the full complement of HSV-2 DNA. (iii) The amount of viral DNA present in the cells varied in different transformed cell lines and ranged from 8 to 32% of the HSV-2 DNA genome in 1 to 3 copies/cell. (iv) Two parallel passages of the same cell line (333-2-29) differed in the amount of viral DNA they contained. We also compared the viral DNA sequences present in (i) one transformed cell line (333-8-9) propagated serially in culture for 80 passages, (ii) a tumor produced by inoculation of a newborn hamster with the 333-8-9 cells, and (iii) a cell line derived from a hamster tumor as above and propagated in culture for 32 passages. The results show that viral DNA present in the hamster tumor and in the cells derived from the tumor had a lower sequence complexity than that present in the original serially passaged 333-8-9 cell line.", "contents": "Herpes simplex virus DNA in transformed cells: sequence complexity in five hamster cell lines and one derived hamster tumor. Analyses of the hybridization kinetics of labeled herpes simplex virus 2 (HSV-2) DNA with DNA from five hamster cell lines transformed by UV light-irradiated HSV-2 revealed the following. (i) Viral DNA sequences were detected in all five cell lines tested. (ii) None of the cell lines contained the full complement of HSV-2 DNA. (iii) The amount of viral DNA present in the cells varied in different transformed cell lines and ranged from 8 to 32% of the HSV-2 DNA genome in 1 to 3 copies/cell. (iv) Two parallel passages of the same cell line (333-2-29) differed in the amount of viral DNA they contained. We also compared the viral DNA sequences present in (i) one transformed cell line (333-8-9) propagated serially in culture for 80 passages, (ii) a tumor produced by inoculation of a newborn hamster with the 333-8-9 cells, and (iii) a cell line derived from a hamster tumor as above and propagated in culture for 32 passages. The results show that viral DNA present in the hamster tumor and in the cells derived from the tumor had a lower sequence complexity than that present in the original serially passaged 333-8-9 cell line."} {"id": "PMID:178928", "title": "Murine mammary tumor virus: characterization of infection of nonmurine cells.", "content": "Murine mammary tumor virus (MuMTV) was used to productively infect feline and mink cells. MuMTV \"proviral\" DNA could be detected in the infected cells by molecular hybridization using radioactive MuMTV complementary DNA as a probe. Kinetic analysis of MuMTV proviral DNA synthesis after infection showed that maximum MuMTV DNA synthesis was achieved by 8 h; however, this was followed by a decline in detectable proviral DNA and eventual stabilization at a lower level. MuMTV synthesis in feline cells was greatly stimulated by the synthetic glucocorticoid, dexamehtasone. On the other hand, MuMTV synthesis in mink cells was relatively at a much higher level in absence of dexamethasone and the stimulation with dexamethasone was not as marked as in the case with infected feline cells. Thermal denaturation of hybrids between MuMTV complementary DNA and infected mink cell RNA revealed no difference from homologous hybrids.", "contents": "Murine mammary tumor virus: characterization of infection of nonmurine cells. Murine mammary tumor virus (MuMTV) was used to productively infect feline and mink cells. MuMTV \"proviral\" DNA could be detected in the infected cells by molecular hybridization using radioactive MuMTV complementary DNA as a probe. Kinetic analysis of MuMTV proviral DNA synthesis after infection showed that maximum MuMTV DNA synthesis was achieved by 8 h; however, this was followed by a decline in detectable proviral DNA and eventual stabilization at a lower level. MuMTV synthesis in feline cells was greatly stimulated by the synthetic glucocorticoid, dexamehtasone. On the other hand, MuMTV synthesis in mink cells was relatively at a much higher level in absence of dexamethasone and the stimulation with dexamethasone was not as marked as in the case with infected feline cells. Thermal denaturation of hybrids between MuMTV complementary DNA and infected mink cell RNA revealed no difference from homologous hybrids."} {"id": "PMID:178929", "title": "Processing of mengovirus precursor polypeptides in the presence of zinc ions and sulfhydryl compounds.", "content": "The effect of zinc ions on the post-translational cleavage of mengovirus polypeptides has been examined. The cleavage of the \"A\" precursor, which gives rise to the capsid proteins, was the most sensitive at concentrations of zinc chloride from 0.1 to 1.0 mM. Beta-mercaptoethanol and dithiothreitol antagonized the zinc-promoted inhibtion of clevage. Our results indicate that zinc ions interfere with the proper folding of the nascent polypeptide precursor rather than inhibit the proteases responsible for the cleavages. Thus, proper folding of mengovirus polypeptide \"A\" appears to be necessary for subsequent processing by proteases.", "contents": "Processing of mengovirus precursor polypeptides in the presence of zinc ions and sulfhydryl compounds. The effect of zinc ions on the post-translational cleavage of mengovirus polypeptides has been examined. The cleavage of the \"A\" precursor, which gives rise to the capsid proteins, was the most sensitive at concentrations of zinc chloride from 0.1 to 1.0 mM. Beta-mercaptoethanol and dithiothreitol antagonized the zinc-promoted inhibtion of clevage. Our results indicate that zinc ions interfere with the proper folding of the nascent polypeptide precursor rather than inhibit the proteases responsible for the cleavages. Thus, proper folding of mengovirus polypeptide \"A\" appears to be necessary for subsequent processing by proteases."} {"id": "PMID:178930", "title": "Rhinovirus multistranded RNA: dependence of the replicative form on the presence of actinomycin D.", "content": "The multistranded and double-stranded RNAs synthesized in HeLa cells infected with rhinovirus in the presence and in the absence of actinomycin D have been characterized by polyacrylamide gel electrophoresis and hybridization studies. The replicative form is only found in infected cells treated with actinomycin D, whereas the replicative intermediate is found in both the presence and the absence of the drug. The significance of these results is discussed.", "contents": "Rhinovirus multistranded RNA: dependence of the replicative form on the presence of actinomycin D. The multistranded and double-stranded RNAs synthesized in HeLa cells infected with rhinovirus in the presence and in the absence of actinomycin D have been characterized by polyacrylamide gel electrophoresis and hybridization studies. The replicative form is only found in infected cells treated with actinomycin D, whereas the replicative intermediate is found in both the presence and the absence of the drug. The significance of these results is discussed."} {"id": "PMID:178931", "title": "Subunit structure of the glycoprotein complex of avian tumor virus.", "content": "Envelope glycoprotein of avian tumor virus is linked by disulfide bonds in a structure that we have designated VGP to stand for viral glycoprotein. VGP appears to contain one molecule of gp85 and one of gp37. Under nonreducing conditions, VGP is the only glycoprotein component that is stable in the presence of ionic detergent, although in the presence of nonionic detergent two or more VGPs are associated in discrete complexes. The disulfide bonds linking viral glycoprotein are formed before release of virus from infected cells.", "contents": "Subunit structure of the glycoprotein complex of avian tumor virus. Envelope glycoprotein of avian tumor virus is linked by disulfide bonds in a structure that we have designated VGP to stand for viral glycoprotein. VGP appears to contain one molecule of gp85 and one of gp37. Under nonreducing conditions, VGP is the only glycoprotein component that is stable in the presence of ionic detergent, although in the presence of nonionic detergent two or more VGPs are associated in discrete complexes. The disulfide bonds linking viral glycoprotein are formed before release of virus from infected cells."} {"id": "PMID:178932", "title": "RNA synthesis in cells infected with herpes simplex virus. XII. Sequence complexity and properties of RNA differing in extent of adenylation.", "content": "Fractionation of polyadenylated RNA from cells infected with herpes simplex virus by affinity chromatography on columns of poly (U) immobilized on glass-fiber filters yielded three major classes of RNA-containing poly(A) chains with average lengths of 30, 50, and 155 adenylate residues [poly(A)30, poly(A)50, poly(A)155]. In contrast, nitrocellulose membranes bound predominantly a fraction of RNA containing poly(A)155. The distribution of cytoplasmic RNA in the three classes was found to be independent of the labeling interval, ranging from 10 min to 6 h. Cytoplasmic poly(A) RNA consisted mainly (57 to 68%) of the poly(A)155 class; this was also the major class (68%) of polyadenylated RNA found in polyribosomes. Nuclear poly(A) RNA consisted largely (42 to 50%) of poly(A)30 class, whereas high-molecular-weight nuclear RNA sedimenting at greater than 45S contained almost exclusively the poly(A)30 tracts. Hybridization experiments involving unlabeled RNA and labeled viral DNA demonstrated the presence of viral RNA sequences complementary to approximately 40% of viral DNA in all polyadenylated RNA classes. Inasmuch as unfractionated cytoplasmic RNA arises from approximately 40% of the viral DNA, we conclude that most, if not all, viral RNA species present in the cytoplasm are adenylated. In contrast to these results, only a fraction of poly(A)155 RNA, complementary to 21% of viral DNA, bound to nitrocellulose filters. The selective binding of poly(A)155 sequences to nitrocellulose filters might be related to its secondary structure, since transcripts homologous to 40% of viral DNA bind to nitrocellulose membranes, provided the RNA is denatured prior to filtration. The data suggest that poly(A) tracts arise by at least two separate steps. The first involves the appearance of poly(A)30 tracts in the high-molecular-weight nuclear transcripts. The second involves polyadenylation to ply(A)50 and poly(A)155 RNA classes concomitant with processing and transport to the cytoplasm.", "contents": "RNA synthesis in cells infected with herpes simplex virus. XII. Sequence complexity and properties of RNA differing in extent of adenylation. Fractionation of polyadenylated RNA from cells infected with herpes simplex virus by affinity chromatography on columns of poly (U) immobilized on glass-fiber filters yielded three major classes of RNA-containing poly(A) chains with average lengths of 30, 50, and 155 adenylate residues [poly(A)30, poly(A)50, poly(A)155]. In contrast, nitrocellulose membranes bound predominantly a fraction of RNA containing poly(A)155. The distribution of cytoplasmic RNA in the three classes was found to be independent of the labeling interval, ranging from 10 min to 6 h. Cytoplasmic poly(A) RNA consisted mainly (57 to 68%) of the poly(A)155 class; this was also the major class (68%) of polyadenylated RNA found in polyribosomes. Nuclear poly(A) RNA consisted largely (42 to 50%) of poly(A)30 class, whereas high-molecular-weight nuclear RNA sedimenting at greater than 45S contained almost exclusively the poly(A)30 tracts. Hybridization experiments involving unlabeled RNA and labeled viral DNA demonstrated the presence of viral RNA sequences complementary to approximately 40% of viral DNA in all polyadenylated RNA classes. Inasmuch as unfractionated cytoplasmic RNA arises from approximately 40% of the viral DNA, we conclude that most, if not all, viral RNA species present in the cytoplasm are adenylated. In contrast to these results, only a fraction of poly(A)155 RNA, complementary to 21% of viral DNA, bound to nitrocellulose filters. The selective binding of poly(A)155 sequences to nitrocellulose filters might be related to its secondary structure, since transcripts homologous to 40% of viral DNA bind to nitrocellulose membranes, provided the RNA is denatured prior to filtration. The data suggest that poly(A) tracts arise by at least two separate steps. The first involves the appearance of poly(A)30 tracts in the high-molecular-weight nuclear transcripts. The second involves polyadenylation to ply(A)50 and poly(A)155 RNA classes concomitant with processing and transport to the cytoplasm."} {"id": "PMID:178933", "title": "Problems in management of primary bilateral germ cell testicular tumors: report of 3 cases and review of literature.", "content": "Bilateral primary germ cell tumors are uncommon but not rare in men with primary testicular tumors. In our series of 78 cases of germ cell tumors 3 (3.8 per cent) were bilateral. In the management of a second neoplasm the same general principles apply as those for the first tumor but one must be aware of the potential complications of radiotion therapy when the total dose for cure of the first and second neoplasms exceeds the tolerance dose of normal tissue and therapy must be modified accordingly. Prognosis is not necessarily poor when a second primary tumor develops and complications can be reduced to a low level with appropriate therapy. Our outline for therapy is presented.", "contents": "Problems in management of primary bilateral germ cell testicular tumors: report of 3 cases and review of literature. Bilateral primary germ cell tumors are uncommon but not rare in men with primary testicular tumors. In our series of 78 cases of germ cell tumors 3 (3.8 per cent) were bilateral. In the management of a second neoplasm the same general principles apply as those for the first tumor but one must be aware of the potential complications of radiotion therapy when the total dose for cure of the first and second neoplasms exceeds the tolerance dose of normal tissue and therapy must be modified accordingly. Prognosis is not necessarily poor when a second primary tumor develops and complications can be reduced to a low level with appropriate therapy. Our outline for therapy is presented."} {"id": "PMID:178934", "title": "Re-exploration for retroperitoneal lymph node metastases from testis tumors.", "content": "Prognosis has been poor for patients with retroperitoneal metastases from non-seminomatous testis tumors that are initially unresectable and persist after chemotherapy and irradiation or those that recur after initial lymphadenectomy. Eleven such patients have had re-explorations at our center and are described herein. In 4 patients only histologically benign teratoma and/or fibrosis was found. Therefore, the presence of a retroperitoneal mass in these circumstances does not necessarily mean that malignant tissue was present. The procedure provided an accurate diagnosis in all patients and permitted the elimination or reduction of subsequent chemotherapy or radiation in 4 patients who had no tumor. In addition, 5 of 7 patients with symptoms caused by bulky masses were improved and 3 patients with unresectable disease had radiopaque markers placed to facilitate subsequent radiotherapy. The operation was often difficult because of retroperitoneal adhesions from previous treatment but there was no significant morbidity and no mortality. Nine patients have survived from 6 months to 4 years and 7 have no evidence of disease. Two patients died of recurrent tumor 2 and 9 months after re-exploration. A good prognosis was indicated if the mass found at re-exploration was completely resectable and contained only histologically benign teratoma and/or fibrous tissue. We believe that re-exploration should be considered for selected patients with testis tumors who have 1) a retroperitoneal mass that appears after initial lymphadenectomy and persists after interval chemotherapy or radiation therapy and 2) retroperitoneal metastases that are initially unresectable and persist after subsequent chemotherapy or radiation therapy.", "contents": "Re-exploration for retroperitoneal lymph node metastases from testis tumors. Prognosis has been poor for patients with retroperitoneal metastases from non-seminomatous testis tumors that are initially unresectable and persist after chemotherapy and irradiation or those that recur after initial lymphadenectomy. Eleven such patients have had re-explorations at our center and are described herein. In 4 patients only histologically benign teratoma and/or fibrosis was found. Therefore, the presence of a retroperitoneal mass in these circumstances does not necessarily mean that malignant tissue was present. The procedure provided an accurate diagnosis in all patients and permitted the elimination or reduction of subsequent chemotherapy or radiation in 4 patients who had no tumor. In addition, 5 of 7 patients with symptoms caused by bulky masses were improved and 3 patients with unresectable disease had radiopaque markers placed to facilitate subsequent radiotherapy. The operation was often difficult because of retroperitoneal adhesions from previous treatment but there was no significant morbidity and no mortality. Nine patients have survived from 6 months to 4 years and 7 have no evidence of disease. Two patients died of recurrent tumor 2 and 9 months after re-exploration. A good prognosis was indicated if the mass found at re-exploration was completely resectable and contained only histologically benign teratoma and/or fibrous tissue. We believe that re-exploration should be considered for selected patients with testis tumors who have 1) a retroperitoneal mass that appears after initial lymphadenectomy and persists after interval chemotherapy or radiation therapy and 2) retroperitoneal metastases that are initially unresectable and persist after subsequent chemotherapy or radiation therapy."} {"id": "PMID:178935", "title": "Colocutaneous fistula: an unusual complication of retroperitoneal lymphadenectomy.", "content": "The unusual complication of colocutaneous fistula following retroperitoneal lymphadenectomy for testis tumor is presented. Etiology, management and prevention are emphasized.", "contents": "Colocutaneous fistula: an unusual complication of retroperitoneal lymphadenectomy. The unusual complication of colocutaneous fistula following retroperitoneal lymphadenectomy for testis tumor is presented. Etiology, management and prevention are emphasized."} {"id": "PMID:178938", "title": "Disseminated herpesvirus infection. Association with primary genital herpes in pregnancy.", "content": "A patient with primary herpes simplex virus (HSV) type 2 genital infection had dissemination in the 37th week of her first pregnancy. This was manifested by severe hepatitis, pancreatitis, and genital lesions. Temporary improvement followed the delivery of a healthy infant by cesarean section. Encephalitis became evident on the third postpartum day, and recovery was complicated by profound bradycardia, possibly due to viral myocarditis. Vidarabine was administered for seven days, and the patient survived with only mild neurologic sequellae. To our knowledge, this the fourth reported case of disseminated herpesvirus infection in pregnancy and the first due to HSV type 2. Pregnancy must be considered as a possible predisposing factor in dissemination of primary HSV infection.", "contents": "Disseminated herpesvirus infection. Association with primary genital herpes in pregnancy. A patient with primary herpes simplex virus (HSV) type 2 genital infection had dissemination in the 37th week of her first pregnancy. This was manifested by severe hepatitis, pancreatitis, and genital lesions. Temporary improvement followed the delivery of a healthy infant by cesarean section. Encephalitis became evident on the third postpartum day, and recovery was complicated by profound bradycardia, possibly due to viral myocarditis. Vidarabine was administered for seven days, and the patient survived with only mild neurologic sequellae. To our knowledge, this the fourth reported case of disseminated herpesvirus infection in pregnancy and the first due to HSV type 2. Pregnancy must be considered as a possible predisposing factor in dissemination of primary HSV infection."} {"id": "PMID:178940", "title": "Further studies of specificity of antibodies contained in antiserum against poliovirus.", "content": "Antigenic components of Mahoney strain (poliovirus type 1) involved in virus neutralization reaction were analyzed with mutant Mahoney strains resistant to inhibitors in equine serum (inhibitor-resistant mutants) by means of the kinetic neutralization test. It was shown that absorption of anti-Mahoney serum with five inhibitor-resistant mutants yielded sera with different antibodies, of which three had distinct specificities and two specificities possibly partly related to one of those three sera. Further, it was found that step wise selection of Mahoney variants resistant to one, two, three and four different inhibitors resulted in gradual deviation of its antigenic composition from that of the original strain. From these results, the possible presence of three or more distinct antigenic determinant sites on the surface of Mahoney strain was indicated.", "contents": "Further studies of specificity of antibodies contained in antiserum against poliovirus. Antigenic components of Mahoney strain (poliovirus type 1) involved in virus neutralization reaction were analyzed with mutant Mahoney strains resistant to inhibitors in equine serum (inhibitor-resistant mutants) by means of the kinetic neutralization test. It was shown that absorption of anti-Mahoney serum with five inhibitor-resistant mutants yielded sera with different antibodies, of which three had distinct specificities and two specificities possibly partly related to one of those three sera. Further, it was found that step wise selection of Mahoney variants resistant to one, two, three and four different inhibitors resulted in gradual deviation of its antigenic composition from that of the original strain. From these results, the possible presence of three or more distinct antigenic determinant sites on the surface of Mahoney strain was indicated."} {"id": "PMID:178943", "title": "Effects of mitogens on glucose oxidation by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia.", "content": "The effects of phytohemagglutinin (PHA), concanavalin a (con A) and endotoxin on glucose oxidation by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia (Cll) were demonstrated without using tissue culture techniques. PHA and CON A had no effect on glucose-6-14C oxidation, but stimulated glucose-1-14C oxidation by normal lmphocytes. This stimulation of glucose-1-14C oxidation occurred within 1 hour and could be prevented by colchicine. In contrast, endotoxin had no effect on either gucose-I-14C or glucose-6-14C oxidation by normal lymphocytes. Lymphocytes from five out of six Cll patients showed low basal rate of gucose-1-14C oxidation by the lymphocytes of these five patients.", "contents": "Effects of mitogens on glucose oxidation by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia. The effects of phytohemagglutinin (PHA), concanavalin a (con A) and endotoxin on glucose oxidation by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia (Cll) were demonstrated without using tissue culture techniques. PHA and CON A had no effect on glucose-6-14C oxidation, but stimulated glucose-1-14C oxidation by normal lmphocytes. This stimulation of glucose-1-14C oxidation occurred within 1 hour and could be prevented by colchicine. In contrast, endotoxin had no effect on either gucose-I-14C or glucose-6-14C oxidation by normal lymphocytes. Lymphocytes from five out of six Cll patients showed low basal rate of gucose-1-14C oxidation by the lymphocytes of these five patients."} {"id": "PMID:178944", "title": "[Ways of drug action on the restorative processes in the myocardium in experimental myocardial infarct].", "content": "On a model of experimental myocardial infarction there is demonstrated the stimulating effect of inosine (most distinctly) and also of stimulants of the nucleic acids synthesis and of retabolil on the formation of the post-infarction scar, the processes of compensatory hyperfunction and hypertrophy, all this finally speeding up the restoration of the myocardial function as a whole. At the root of this research carried out on 276 rabbits there lie histological, histochemical, electron microscopic, biochemical, electrographic findings and determination of the intracardiac hemodynamics.", "contents": "[Ways of drug action on the restorative processes in the myocardium in experimental myocardial infarct]. On a model of experimental myocardial infarction there is demonstrated the stimulating effect of inosine (most distinctly) and also of stimulants of the nucleic acids synthesis and of retabolil on the formation of the post-infarction scar, the processes of compensatory hyperfunction and hypertrophy, all this finally speeding up the restoration of the myocardial function as a whole. At the root of this research carried out on 276 rabbits there lie histological, histochemical, electron microscopic, biochemical, electrographic findings and determination of the intracardiac hemodynamics."} {"id": "PMID:178945", "title": "[Changes in blood lipid content with aging and genetic studies of ischemic heart disease].", "content": "Results are presented on the study of lipid metabolism in normal individuals of different are groups with reference to the hereditary taintness as to ischaelic heart disease, and the results of correlation analysis of the level of some lipid indices of the blood of patients with ischaemic heart disease and of their relatives. In young normal individuals, whose family history is hereditary teinted with ischaemic heart disease, the level of total lipids, cholesterol, cholesterol of beta-lipoproteids, beta-lipoproteids and non-estherified fatty acids was statistically significantly higher than in the control group. In the older age groups, however, this difference becomes insignificant. The blood level of cholesterol and beta-lipoproteids is determined by genetic factors to a higher degree than the level of total lipids. The introduction of a correction factor into the correlation analysis of the above biochemical parameters indicates the changes developing with age in the proportional role of the environmental and genetic factors in the lipid metabolism disorders, the importance of the environmental factors progressively growing.", "contents": "[Changes in blood lipid content with aging and genetic studies of ischemic heart disease]. Results are presented on the study of lipid metabolism in normal individuals of different are groups with reference to the hereditary taintness as to ischaelic heart disease, and the results of correlation analysis of the level of some lipid indices of the blood of patients with ischaemic heart disease and of their relatives. In young normal individuals, whose family history is hereditary teinted with ischaemic heart disease, the level of total lipids, cholesterol, cholesterol of beta-lipoproteids, beta-lipoproteids and non-estherified fatty acids was statistically significantly higher than in the control group. In the older age groups, however, this difference becomes insignificant. The blood level of cholesterol and beta-lipoproteids is determined by genetic factors to a higher degree than the level of total lipids. The introduction of a correction factor into the correlation analysis of the above biochemical parameters indicates the changes developing with age in the proportional role of the environmental and genetic factors in the lipid metabolism disorders, the importance of the environmental factors progressively growing."} {"id": "PMID:178946", "title": "[The etiology of epidemic keratoconjunctivities (author's transl)].", "content": "In 93 patients (mostly sporadic cases) with suspected EKC an infection with adenoviruses was proved by virological and serological methods in 54 cases. Types 8, 3, 7, 19, 4, and 14 were found in 38, 6, 5, 3, 1, and 1 cases respectively. 33 out of 48 patients with clinically typical EKC had an infection with type 8. From the patients without adenoviral infection, the absence of which having been proved by extensive serological tests, 7 showed a typical EKC. The symptoms considered as relatively typical (hyperemia and oedema of the plica and caruncle, subepithelial corneal infiltrates) were not confined to patients with adenovirus infection; thus they cannot be considered as characteristic for this group of viruses. The results indicate the need for a specific diagnosis in cases of suspected EKC, which should include virus isolation from conjunctival swabs as well as the demonstration of antibody titer rises by various serological tests. EKC is to be considered as a clinical and epidemiological rather than as an etiological entity.", "contents": "[The etiology of epidemic keratoconjunctivities (author's transl)]. In 93 patients (mostly sporadic cases) with suspected EKC an infection with adenoviruses was proved by virological and serological methods in 54 cases. Types 8, 3, 7, 19, 4, and 14 were found in 38, 6, 5, 3, 1, and 1 cases respectively. 33 out of 48 patients with clinically typical EKC had an infection with type 8. From the patients without adenoviral infection, the absence of which having been proved by extensive serological tests, 7 showed a typical EKC. The symptoms considered as relatively typical (hyperemia and oedema of the plica and caruncle, subepithelial corneal infiltrates) were not confined to patients with adenovirus infection; thus they cannot be considered as characteristic for this group of viruses. The results indicate the need for a specific diagnosis in cases of suspected EKC, which should include virus isolation from conjunctival swabs as well as the demonstration of antibody titer rises by various serological tests. EKC is to be considered as a clinical and epidemiological rather than as an etiological entity."} {"id": "PMID:178947", "title": "[Collagen metabolism and mineralization of uremic bone--aspects of the molecular pathology of renal osteodystrophy].", "content": "Importance sequelae of uremia are hormonal changes in calcium homeostasis combined with chronic calcium imbalance causing structural alteration and functional insufficiency of bone. Morphological findings of the so called renal osteodystrophy are osteomalacia, osteitis fibrosa and osteoporosis. Osteitis fibrosa and abnormal skeletal metabolism (changes of collagen turnover, insufficient maturation of stable bone crystals) impair the mechanical qualities of bone. Probably the uremia per se influences the collagen metabolism; additional factors such as secondary hyperparathyroidism and deficiency of vitamin D3 are discussed.", "contents": "[Collagen metabolism and mineralization of uremic bone--aspects of the molecular pathology of renal osteodystrophy]. Importance sequelae of uremia are hormonal changes in calcium homeostasis combined with chronic calcium imbalance causing structural alteration and functional insufficiency of bone. Morphological findings of the so called renal osteodystrophy are osteomalacia, osteitis fibrosa and osteoporosis. Osteitis fibrosa and abnormal skeletal metabolism (changes of collagen turnover, insufficient maturation of stable bone crystals) impair the mechanical qualities of bone. Probably the uremia per se influences the collagen metabolism; additional factors such as secondary hyperparathyroidism and deficiency of vitamin D3 are discussed."} {"id": "PMID:178948", "title": "[Management of slipped epiphyses in renal osteodystrophy (author's transl)].", "content": "Epiphyseal slipping in uraemia differs strikingly from juvenile epiphyseal slipping with respect to pathology and therapy. Based on our own experience with the treatment of 8 uraemic children with epiphyseal slipping, an effort was made to establish the respective indications for conservative and surgical treatment. Mechanical stabilization of slipped epiphyses was achieved within a few weeks without any surgery and usually without parathyreoidectomy by vitamin D3 alone. The initial dose was 10,000 to 30,000 I.U./day, the total curative dose 1.8 to 5.6 millions I.U. Prolonged immobilization was unnecessary. Rising urinary calcium excretion was a valuable indicator of vitamin D intoxication even in advanced renal failure. In one case, pronounced metaphyseal deformations (distal femur, distal tibia) required surgical correction before the ability to walk normally was restored. - The following therapeutical approach is recommended: metabolic bone disease must be cured by vitamin D therapy with or without parathyreoidectomy. Osteotomy to correct metaphyseal deformities or coxa vara epiphysaria never should be performed before metabolic bone disease is healed.", "contents": "[Management of slipped epiphyses in renal osteodystrophy (author's transl)]. Epiphyseal slipping in uraemia differs strikingly from juvenile epiphyseal slipping with respect to pathology and therapy. Based on our own experience with the treatment of 8 uraemic children with epiphyseal slipping, an effort was made to establish the respective indications for conservative and surgical treatment. Mechanical stabilization of slipped epiphyses was achieved within a few weeks without any surgery and usually without parathyreoidectomy by vitamin D3 alone. The initial dose was 10,000 to 30,000 I.U./day, the total curative dose 1.8 to 5.6 millions I.U. Prolonged immobilization was unnecessary. Rising urinary calcium excretion was a valuable indicator of vitamin D intoxication even in advanced renal failure. In one case, pronounced metaphyseal deformations (distal femur, distal tibia) required surgical correction before the ability to walk normally was restored. - The following therapeutical approach is recommended: metabolic bone disease must be cured by vitamin D therapy with or without parathyreoidectomy. Osteotomy to correct metaphyseal deformities or coxa vara epiphysaria never should be performed before metabolic bone disease is healed."} {"id": "PMID:178959", "title": "Carrier state of antibody and viruses in a mouse breeding colony persistently infected with Sendai and mouse hepatitis viruses.", "content": "In a large-scale mouse breeder colony persistently infected with Sendai and mouse hepatitis viruses, most adult breeders 8 wk or more of age were shown to have antibodies to both viruses when monitored over a periof of 20 mo. Antibody to Sendai virus, apparently transmitted from the dam, was detected in 76% and 2% of mice aged 3 and 4 wk. respectively, and 64% and 100% of mice aged 6 and 8 wk, respectively. By seroconversion of sentinel cage-mates, a Sendai virus-carrier state was demonstrated with 6-wk-old mice but not with those either 4 wk or 10 wk of age, suggesting that breeder candidates about 6 wk of age may play an important role in establishing and perpetuating Sendai infection in this breeding colony. With mouse hepatitis virus, however, mice aged 4 wk or older seem to be effective transmitters of the virus, while some of these mice were found to have antibody to the virus.", "contents": "Carrier state of antibody and viruses in a mouse breeding colony persistently infected with Sendai and mouse hepatitis viruses. In a large-scale mouse breeder colony persistently infected with Sendai and mouse hepatitis viruses, most adult breeders 8 wk or more of age were shown to have antibodies to both viruses when monitored over a periof of 20 mo. Antibody to Sendai virus, apparently transmitted from the dam, was detected in 76% and 2% of mice aged 3 and 4 wk. respectively, and 64% and 100% of mice aged 6 and 8 wk, respectively. By seroconversion of sentinel cage-mates, a Sendai virus-carrier state was demonstrated with 6-wk-old mice but not with those either 4 wk or 10 wk of age, suggesting that breeder candidates about 6 wk of age may play an important role in establishing and perpetuating Sendai infection in this breeding colony. With mouse hepatitis virus, however, mice aged 4 wk or older seem to be effective transmitters of the virus, while some of these mice were found to have antibody to the virus."} {"id": "PMID:178960", "title": "Criteria for producing high quality animals for research.", "content": "The criteria for the breeding or purchase of high quality research animals in general, and of dogs, cats, monkeys, rats, mice, guinea pigs, and rabbits were discussed. The reasons for using high quality animals are: economic, accuracy and reproducibility of results, no effects due to the presence of pathogens, and reduction of human health hazards.", "contents": "Criteria for producing high quality animals for research. The criteria for the breeding or purchase of high quality research animals in general, and of dogs, cats, monkeys, rats, mice, guinea pigs, and rabbits were discussed. The reasons for using high quality animals are: economic, accuracy and reproducibility of results, no effects due to the presence of pathogens, and reduction of human health hazards."} {"id": "PMID:178961", "title": "Effects of sodium periodate on platelet functions.", "content": "Removal of N-acetylneuraminic acid from the platelet surface causes rapid removal of platelets from the circulation but causes little change in other platelet functions. We have now investigated the effects of sodium periodate which is thought to oxidize the sialic acid of glycoproteins on cell surfaces and has been shown to affect the functions of other cells. NaIO4 (1 to 10 mm) caused aggregation of stirred suspensions of washed platelets from rabbits. Calcium was required in the suspending medium for NaIO4-induced aggregation. Aggregation was not accompanied by the release of amine storage granule contents nor by cell lysis. Aggregation induced by NaIO4 was not inhibited by creatine phosphate-creatine phosphokinase, by platelet inhibitors that raise platelet cyclic AMP levels such as prostaglandin E1 or methylxanthines, by agents that modify platelet surface--SH groups (N-ethylmaleimide, p-chloromercuribenzene sulfonate), nor by cytochalasin B and/or colchicine which interfere with platelet contractile processes. Drugs such as acetylsalicyclic acid, penicillin G, or cephalothin had no effect on NaIO4-induced aggregation. NaIO4-induced aggregation was practically independent of platelet metabolism since it was not affected by low temperatures and was only slightly inhibited by a combination of antimycin and iodoacetate. Periodate treatment enhanced CO2 production by platelets. When rabbit platelets were pretreated, without stirring, with NaIO4 (0.01 to 1 mm), they did not aggregate. They retained their disc shape and granule contents. However, this pretreatment with NaIO4 inhibited aggregation induced by ADP and inhibited both aggregation and release induced by collagen, thrombin, arachidonic acid, and the ionophore A23,187. The extent of inhibition corresponded to the concentration of NaIO4 used to pretreat the platelets. In contrast, concanavalin A-induced aggregation was unchanged by NaIO4 pretreatment. When NaIO4 oxidation was followed by sodium borohydride (NaBH4) reduction, the effects caused by NaIO4 pretreatment on ADP-induced aggregation and collagen- or thrombin-induced aggregation and release were partially reversed. Pretreatment with NaIO4 also diminished the rate of serotonin uptake and decreased the ability of platelets to adhere to collagen-coated surfaces or to the subendothelial structures of the rabbit aorta. Platelets which had been treated with NaIO4 and then reinfused into rabbits did not survive, and in this way were similar to platelets from which surface sialic acid had been removed by neuraminidase treatment. Since NaIO4 has been shown to oxidize sialic acid on red cell membranes, it seems probably that alteration of surface sialic acid resulted in recognition of the periodate-treated platelets as \"foreign\" by the reticuloendothelial system. When NaIO4 oxidation was followed by NaBH4 reduction, platelet survival returned toward normal values.", "contents": "Effects of sodium periodate on platelet functions. Removal of N-acetylneuraminic acid from the platelet surface causes rapid removal of platelets from the circulation but causes little change in other platelet functions. We have now investigated the effects of sodium periodate which is thought to oxidize the sialic acid of glycoproteins on cell surfaces and has been shown to affect the functions of other cells. NaIO4 (1 to 10 mm) caused aggregation of stirred suspensions of washed platelets from rabbits. Calcium was required in the suspending medium for NaIO4-induced aggregation. Aggregation was not accompanied by the release of amine storage granule contents nor by cell lysis. Aggregation induced by NaIO4 was not inhibited by creatine phosphate-creatine phosphokinase, by platelet inhibitors that raise platelet cyclic AMP levels such as prostaglandin E1 or methylxanthines, by agents that modify platelet surface--SH groups (N-ethylmaleimide, p-chloromercuribenzene sulfonate), nor by cytochalasin B and/or colchicine which interfere with platelet contractile processes. Drugs such as acetylsalicyclic acid, penicillin G, or cephalothin had no effect on NaIO4-induced aggregation. NaIO4-induced aggregation was practically independent of platelet metabolism since it was not affected by low temperatures and was only slightly inhibited by a combination of antimycin and iodoacetate. Periodate treatment enhanced CO2 production by platelets. When rabbit platelets were pretreated, without stirring, with NaIO4 (0.01 to 1 mm), they did not aggregate. They retained their disc shape and granule contents. However, this pretreatment with NaIO4 inhibited aggregation induced by ADP and inhibited both aggregation and release induced by collagen, thrombin, arachidonic acid, and the ionophore A23,187. The extent of inhibition corresponded to the concentration of NaIO4 used to pretreat the platelets. In contrast, concanavalin A-induced aggregation was unchanged by NaIO4 pretreatment. When NaIO4 oxidation was followed by sodium borohydride (NaBH4) reduction, the effects caused by NaIO4 pretreatment on ADP-induced aggregation and collagen- or thrombin-induced aggregation and release were partially reversed. Pretreatment with NaIO4 also diminished the rate of serotonin uptake and decreased the ability of platelets to adhere to collagen-coated surfaces or to the subendothelial structures of the rabbit aorta. Platelets which had been treated with NaIO4 and then reinfused into rabbits did not survive, and in this way were similar to platelets from which surface sialic acid had been removed by neuraminidase treatment. Since NaIO4 has been shown to oxidize sialic acid on red cell membranes, it seems probably that alteration of surface sialic acid resulted in recognition of the periodate-treated platelets as \"foreign\" by the reticuloendothelial system. When NaIO4 oxidation was followed by NaBH4 reduction, platelet survival returned toward normal values."} {"id": "PMID:178962", "title": "Electron microscopic features of lipoprotein-glycosaminoglycan complexes from human atherosclerotic plaques.", "content": "Lipoprotein-glycosaminoglycan (GAG) complexes were isolated from fibrous plaque lesions of human aortas and examined by electron microscopy. After fractionation by gel chromatography and ultracentrifugation, both very low density lopoprotein-GAG and low density lopoprotein-GAG complexes showed particles which were mainly 1,000 to 2,000 A in diameter. Occasional large aggregations 3,000 to 10,000 A in diameter were seen after gel filtration and in the very low density lipoprotein fraction of complexes. In general, the complexes were larger than serum very low density lipoprotein and low density lipoprotein, although serum very low density lipoprotein particles ranged from 250 to 2,000 A. In vitro low density lipoprotein-heparin complexes consisted of spherical particles generally 1,000 to 2,000 A in diameter formed by the aggregation and coalescing of smaller low density liproprotein particles in the presence of heparin and Ca2+. These observations support a concept that GAG of the aortic intimal \"ground substance\" sequester certain serum lipoproteins in a manner similar to in vitro complexing of lipoproteins and GAG in the presence of Ca2+.", "contents": "Electron microscopic features of lipoprotein-glycosaminoglycan complexes from human atherosclerotic plaques. Lipoprotein-glycosaminoglycan (GAG) complexes were isolated from fibrous plaque lesions of human aortas and examined by electron microscopy. After fractionation by gel chromatography and ultracentrifugation, both very low density lopoprotein-GAG and low density lopoprotein-GAG complexes showed particles which were mainly 1,000 to 2,000 A in diameter. Occasional large aggregations 3,000 to 10,000 A in diameter were seen after gel filtration and in the very low density lipoprotein fraction of complexes. In general, the complexes were larger than serum very low density lipoprotein and low density lipoprotein, although serum very low density lipoprotein particles ranged from 250 to 2,000 A. In vitro low density lipoprotein-heparin complexes consisted of spherical particles generally 1,000 to 2,000 A in diameter formed by the aggregation and coalescing of smaller low density liproprotein particles in the presence of heparin and Ca2+. These observations support a concept that GAG of the aortic intimal \"ground substance\" sequester certain serum lipoproteins in a manner similar to in vitro complexing of lipoproteins and GAG in the presence of Ca2+."} {"id": "PMID:178964", "title": "Concordance of electrocardiographic and scintigraphic criteria of myocardial injury after cardiac surgery.", "content": "The concordance of transmural electrocardiographic (ECG) changes and myocardial infarct imaging in detecting myocardial injury in the perioperative period was evaluated in 50 patients undergoing coronary artery bypass surgery and in 6 patients without coronary artery disease undergoing valve replacement. Scintigraphy with technetium-99m (Sn) labeled pyrophosphate was performed 3 to 7 days after surgery. Plasma creatine phosphokinase (CPK) levels were determined preoperatively and daily for 7 days postoperatively. Plasma MB-CPK was assayed fluorometrically in samples obtained at 12 hour intervals for 36 hours. Total CPK and MB-CPK concentrations were normal in all patients preoperatively but increased in every patient postoperatively. A total of 8 patients (16%) had evidence of perioperative infarction. Six of these patients (12%) with coronary artery disease exhibited abnormal images after bypass surgery, associated with transmural ECG changes in each case. The other 2 patients (4%) with coronary artery disease who had abnormal images were among 4 patients who developed bundle branch block after the operation. Abnormal images did not occur in any patient undergoing valve replacement despite total CPK and MB-CPK elevations. These results indicate that total CPK and MB-CPK elevations occur consistently after cardiac surgery and cannot be relied upon for detection of transmural infarction. Furthermore, new conduction defects may not necessarily be a sign of perioperative infarction, and infarct imaging may be a useful means of establishing myocardial infarction in this group of patients.", "contents": "Concordance of electrocardiographic and scintigraphic criteria of myocardial injury after cardiac surgery. The concordance of transmural electrocardiographic (ECG) changes and myocardial infarct imaging in detecting myocardial injury in the perioperative period was evaluated in 50 patients undergoing coronary artery bypass surgery and in 6 patients without coronary artery disease undergoing valve replacement. Scintigraphy with technetium-99m (Sn) labeled pyrophosphate was performed 3 to 7 days after surgery. Plasma creatine phosphokinase (CPK) levels were determined preoperatively and daily for 7 days postoperatively. Plasma MB-CPK was assayed fluorometrically in samples obtained at 12 hour intervals for 36 hours. Total CPK and MB-CPK concentrations were normal in all patients preoperatively but increased in every patient postoperatively. A total of 8 patients (16%) had evidence of perioperative infarction. Six of these patients (12%) with coronary artery disease exhibited abnormal images after bypass surgery, associated with transmural ECG changes in each case. The other 2 patients (4%) with coronary artery disease who had abnormal images were among 4 patients who developed bundle branch block after the operation. Abnormal images did not occur in any patient undergoing valve replacement despite total CPK and MB-CPK elevations. These results indicate that total CPK and MB-CPK elevations occur consistently after cardiac surgery and cannot be relied upon for detection of transmural infarction. Furthermore, new conduction defects may not necessarily be a sign of perioperative infarction, and infarct imaging may be a useful means of establishing myocardial infarction in this group of patients."} {"id": "PMID:178973", "title": "Lipids of Klebsiella pneumoniae: the presence of phosphatidyl choline in succinate-grown cells.", "content": "The carbon and energy source for aerobically grown cultures of Klebsiella pneumoniae profoundly influenced the total lipid content and phosphatide composition. Glucose-grown cells contained 13% lipid, 56% of which was phospholipids. Succinate-grown cells contained 8% lipid, 66% of which was phospholipids. The predominant phosphatides of glucose-grown cells were phosphatidyl ethanolamine, 82%; phosphatidyl glycerol, 4.5%; phosphatidic acid, 5%; cardiolipin, 6.5%; phosphatidyl serine; and trace amounts of unidentified phosphatides. Phosphatides of succinate-grown cells were phosphatidyl ethanolamine, 38%; diphosphatidyl glycerol, 14%; phosphatidyl glycerol, 13%; phosphatidyl choline, 14.5%; phosphatidyl serine, 6%; phosphatidic acid, 4%; and 10% unknown lipids. No trace of phosphatidyl choline was found in glucose-grown cells.", "contents": "Lipids of Klebsiella pneumoniae: the presence of phosphatidyl choline in succinate-grown cells. The carbon and energy source for aerobically grown cultures of Klebsiella pneumoniae profoundly influenced the total lipid content and phosphatide composition. Glucose-grown cells contained 13% lipid, 56% of which was phospholipids. Succinate-grown cells contained 8% lipid, 66% of which was phospholipids. The predominant phosphatides of glucose-grown cells were phosphatidyl ethanolamine, 82%; phosphatidyl glycerol, 4.5%; phosphatidic acid, 5%; cardiolipin, 6.5%; phosphatidyl serine; and trace amounts of unidentified phosphatides. Phosphatides of succinate-grown cells were phosphatidyl ethanolamine, 38%; diphosphatidyl glycerol, 14%; phosphatidyl glycerol, 13%; phosphatidyl choline, 14.5%; phosphatidyl serine, 6%; phosphatidic acid, 4%; and 10% unknown lipids. No trace of phosphatidyl choline was found in glucose-grown cells."} {"id": "PMID:178974", "title": "Free radical reactions of peroxidizing lipids with amino acids and proteins: an ESR study.", "content": "Free radical transfer from oxidizing methyl linoleate to amino acids and proteins was studied in dry model systems incubated for periods up to 20 days. Electron spin resonance was used to study free radical production. Free radicals were detectable in the amino acids lysine, arginine, histidine, tryptophan, and cysteine. Reduced glutathione and, to a limited extent, cystine also gave free radical signals. Free radicals produced in proteins primarily showed central singlet lines, attributable to carbon-centered radicals, with g= 2.004+/- 0.001. Sulfhydryl proteins also exhibited downfield shoulders at g approximately equal to 2.015 and 2.023 that were essentially identical to peaks observed in cysteine and reduced gluathione. The field positions of sulfur resonace in cysteine and proteins suggested a sulfur-oxygen complex rather than thiyl radicals.", "contents": "Free radical reactions of peroxidizing lipids with amino acids and proteins: an ESR study. Free radical transfer from oxidizing methyl linoleate to amino acids and proteins was studied in dry model systems incubated for periods up to 20 days. Electron spin resonance was used to study free radical production. Free radicals were detectable in the amino acids lysine, arginine, histidine, tryptophan, and cysteine. Reduced glutathione and, to a limited extent, cystine also gave free radical signals. Free radicals produced in proteins primarily showed central singlet lines, attributable to carbon-centered radicals, with g= 2.004+/- 0.001. Sulfhydryl proteins also exhibited downfield shoulders at g approximately equal to 2.015 and 2.023 that were essentially identical to peaks observed in cysteine and reduced gluathione. The field positions of sulfur resonace in cysteine and proteins suggested a sulfur-oxygen complex rather than thiyl radicals."} {"id": "PMID:178979", "title": "Neonatal familial hypobeta-lipoproteinemia.", "content": "A kindred with four generation vertical transmission of familial hypobeta-lipoproteinemia was ascertained by measurement of low levels of cord blood low density lipoprotein cholesterol (C-LDL) in a propositus neonate. Measurement of cord blood C-LDL in conjunction with family studies allows the neonatal diagnosis of familial hypobetalipoproteinemia.", "contents": "Neonatal familial hypobeta-lipoproteinemia. A kindred with four generation vertical transmission of familial hypobeta-lipoproteinemia was ascertained by measurement of low levels of cord blood low density lipoprotein cholesterol (C-LDL) in a propositus neonate. Measurement of cord blood C-LDL in conjunction with family studies allows the neonatal diagnosis of familial hypobetalipoproteinemia."} {"id": "PMID:178975", "title": "[Characteristics of manifestations of border effect in electroroentgenobronchography].", "content": "Specificity of the image reflecting the outlines of the bronchial lumena on the electroroentgenograms is explained by the manifestation of the border effect. The latter is caused by the non-uniformity of the electric field over the surface of the selenium layer with a regular distribution of charges. With electroroentgenography of sharply contrasted objects in a little contrast medium the potential relief has highly pronounced differences, this leading to distorsion of the dimensions and the shape of the objects under examination. When interpreting electroroentgenograms these specific features should be taken into consideration. In constructing improved medical radiographic equipment it will be advisable to envisage the possibility of controlling the said effect.", "contents": "[Characteristics of manifestations of border effect in electroroentgenobronchography]. Specificity of the image reflecting the outlines of the bronchial lumena on the electroroentgenograms is explained by the manifestation of the border effect. The latter is caused by the non-uniformity of the electric field over the surface of the selenium layer with a regular distribution of charges. With electroroentgenography of sharply contrasted objects in a little contrast medium the potential relief has highly pronounced differences, this leading to distorsion of the dimensions and the shape of the objects under examination. When interpreting electroroentgenograms these specific features should be taken into consideration. In constructing improved medical radiographic equipment it will be advisable to envisage the possibility of controlling the said effect."} {"id": "PMID:178980", "title": "Effect of sex hormones on protamine inactivated and resistant postheparin plasma lipases.", "content": "Effects of estrogens and the synthetic anabolic-androgenic steroid, Oxandrolone, on extrahepatic (protamine inactivated) and hepatic (protamine resistant) lipases in postheparin plasma, were assessed in 15 subjects with familial hypertriglyceridemia. In six women receiving conjugated equine estrogen (1.25 mg/day), mean (+/- SE) postheparin protemine inactivated triglyceride lipase (PI-TGL) was depressed to 0.23 +/- 0.10 mumol FFA/ml/hr, and protamine resistant lipase was depressed to 5.3 +/- 0.5 mumol FFA/ml/hr. In the 2-wk period after estrogens were discontinued, PI-TGL remained depressed, 0.54 +/- 0.24, while PR-TGL increased to 7.3 +/- 0.88, p=less than 0.05. Mean triglycerides fell insignificantly from 628 +/- 136 to 447 +/- 44 mg/100 ml when estrogens were discontinued. There was no significant correlation between changes in PR-TGL and triglycerides when estrogens were stopped. In four women with familial hypertriglyceridemia, Oxandrolone significantly increased PR-TGL in two, increased PI-TGL in three, and reduced triglycerides in two. In five men with familial hypertriglyceridemia, Oxandrolone reduced triglycerides in four, increased PR-TGL in four, but had no effect on PI-TGL. For the nine hypertriglyceridemic subjects increments in PR-TGL failed to correlate significantly with decrements in triglyceride, (r=0.309, p is greater than 0.1). Selective alteration of PR-TGL and PI-TGL by estrogens and Oxandrolone may provide an approach to better understanding of the interaction of lipases and triglycerides in familial and acquired hypertriglyceridemia.", "contents": "Effect of sex hormones on protamine inactivated and resistant postheparin plasma lipases. Effects of estrogens and the synthetic anabolic-androgenic steroid, Oxandrolone, on extrahepatic (protamine inactivated) and hepatic (protamine resistant) lipases in postheparin plasma, were assessed in 15 subjects with familial hypertriglyceridemia. In six women receiving conjugated equine estrogen (1.25 mg/day), mean (+/- SE) postheparin protemine inactivated triglyceride lipase (PI-TGL) was depressed to 0.23 +/- 0.10 mumol FFA/ml/hr, and protamine resistant lipase was depressed to 5.3 +/- 0.5 mumol FFA/ml/hr. In the 2-wk period after estrogens were discontinued, PI-TGL remained depressed, 0.54 +/- 0.24, while PR-TGL increased to 7.3 +/- 0.88, p=less than 0.05. Mean triglycerides fell insignificantly from 628 +/- 136 to 447 +/- 44 mg/100 ml when estrogens were discontinued. There was no significant correlation between changes in PR-TGL and triglycerides when estrogens were stopped. In four women with familial hypertriglyceridemia, Oxandrolone significantly increased PR-TGL in two, increased PI-TGL in three, and reduced triglycerides in two. In five men with familial hypertriglyceridemia, Oxandrolone reduced triglycerides in four, increased PR-TGL in four, but had no effect on PI-TGL. For the nine hypertriglyceridemic subjects increments in PR-TGL failed to correlate significantly with decrements in triglyceride, (r=0.309, p is greater than 0.1). Selective alteration of PR-TGL and PI-TGL by estrogens and Oxandrolone may provide an approach to better understanding of the interaction of lipases and triglycerides in familial and acquired hypertriglyceridemia."} {"id": "PMID:178981", "title": "Quantitation of apolipoprotein A-I of human plasma high density lipoprotein.", "content": "High density lipoproteins (HDL) may be controlled via their major apolipoprotein, A-I. To study this apolipoprotein, a simple, precise, and accurate immunodiffusion assay for A-I was developed and applied in a sample of Bell Telephone Company employees. A-I showed a slight increase with age in men (r=0.11, n=263) and women (r=0.15, n=257). A-I correlated closely with HDL cholesterol (r=0.72). It was weakly related to total triglyceride in women (r=0.24) but was inversely related in men (r=-0.17). Women on estrogen had the highest A-I levels (149 mg/dl +/- 26, x +/- S.D., n=29, p is less than 0.05), followed by women on combination oral contraceptives (141 +/- 26, n=80) whereas women on no medication had lower levels (129 +/- 25, n=99, p is less than 0.01) but men had the lowest levels (120 +/- 20, p is less than 0.01) In a separate group of 14 women given estrogen for 2 wks (1 mug/kg/day), A-I increased by 24%. Thus A-I is increased by exogenous and, most likely, endogenous estrogen, Among hyperlipidemic referral subjects, those with hypercholesterolemia (n=43) and hypertriglyceridemic women (n=33) had normal A-I levels. Among hypertriglyceridemic men both A-I and HDL cholesterol values were decreased (115 +/- 20, p is less than 0.01 and 37 +/- 3, p is less than 0.01, respectively, n=68) but were significantly lower among a group of myocardial infarction survivors (107 +/- 16, p is less than 0.01, and 27 +/- 6, p is less than 0.01, respectively, n=24). High density lipoprotein levels and the content of cholesterol in HDL associated with A-I appear to be decreased in coronary heart disease.", "contents": "Quantitation of apolipoprotein A-I of human plasma high density lipoprotein. High density lipoproteins (HDL) may be controlled via their major apolipoprotein, A-I. To study this apolipoprotein, a simple, precise, and accurate immunodiffusion assay for A-I was developed and applied in a sample of Bell Telephone Company employees. A-I showed a slight increase with age in men (r=0.11, n=263) and women (r=0.15, n=257). A-I correlated closely with HDL cholesterol (r=0.72). It was weakly related to total triglyceride in women (r=0.24) but was inversely related in men (r=-0.17). Women on estrogen had the highest A-I levels (149 mg/dl +/- 26, x +/- S.D., n=29, p is less than 0.05), followed by women on combination oral contraceptives (141 +/- 26, n=80) whereas women on no medication had lower levels (129 +/- 25, n=99, p is less than 0.01) but men had the lowest levels (120 +/- 20, p is less than 0.01) In a separate group of 14 women given estrogen for 2 wks (1 mug/kg/day), A-I increased by 24%. Thus A-I is increased by exogenous and, most likely, endogenous estrogen, Among hyperlipidemic referral subjects, those with hypercholesterolemia (n=43) and hypertriglyceridemic women (n=33) had normal A-I levels. Among hypertriglyceridemic men both A-I and HDL cholesterol values were decreased (115 +/- 20, p is less than 0.01 and 37 +/- 3, p is less than 0.01, respectively, n=68) but were significantly lower among a group of myocardial infarction survivors (107 +/- 16, p is less than 0.01, and 27 +/- 6, p is less than 0.01, respectively, n=24). High density lipoprotein levels and the content of cholesterol in HDL associated with A-I appear to be decreased in coronary heart disease."} {"id": "PMID:178982", "title": "Mechanism of plasma cyclic AMP response to hypoglycemia in man.", "content": "The effect of insulin-induced hypoglycemia on plasma cyclic AMP levels was studied in normal volunteers, adrenalectomized, and sympathectomized subjects. Significant increases in plasma glucagon were observed in all groups. Normal subjects all had two- to threefold rises in plasma cAMP while no response was seen in any adrenalectomized or sympathectomized subject. These findings suggest that the mechanism for enhanced plasma cAMP release during insulin-induced hypoglycemia is catecholamine dependent. Glucagon does not contribute significantly to this response.", "contents": "Mechanism of plasma cyclic AMP response to hypoglycemia in man. The effect of insulin-induced hypoglycemia on plasma cyclic AMP levels was studied in normal volunteers, adrenalectomized, and sympathectomized subjects. Significant increases in plasma glucagon were observed in all groups. Normal subjects all had two- to threefold rises in plasma cAMP while no response was seen in any adrenalectomized or sympathectomized subject. These findings suggest that the mechanism for enhanced plasma cAMP release during insulin-induced hypoglycemia is catecholamine dependent. Glucagon does not contribute significantly to this response."} {"id": "PMID:178984", "title": "Colorectal carcinoma: a prospect clinicopathological study.", "content": "The clinical and pathological findings in 200 consecutive cases of colorectal carcinoma treated by surgical resection have been recorded and subjected to computer analysis. This is the initial report from a long-term prospective survey of this disease. The two most frequent presenting symptoms were altered bowel habit (51.5%) and bleeding (49.5%). Symptoms due to anaemia occurred in 16% of cases and acute obstruction in 13.5% of cases. The value of the various investigations in establishing the diagnosis is discusses. At the time of resection the disease had already reached an advanced stage in a majority of the patients. In 26% of cases it was known that complete resection of tumour tissue had not been achieved. A direct relationship between stage of spread and histological grade of malignancy was noted. The incidence of advanced stage, high histological grade and mucinous tumours was greatest in the right side of the colon. A study of early carcinomas has confirmed that many have arisen from benign epithelial neoplastic polyps. The significance of these observations is discussed.", "contents": "Colorectal carcinoma: a prospect clinicopathological study. The clinical and pathological findings in 200 consecutive cases of colorectal carcinoma treated by surgical resection have been recorded and subjected to computer analysis. This is the initial report from a long-term prospective survey of this disease. The two most frequent presenting symptoms were altered bowel habit (51.5%) and bleeding (49.5%). Symptoms due to anaemia occurred in 16% of cases and acute obstruction in 13.5% of cases. The value of the various investigations in establishing the diagnosis is discusses. At the time of resection the disease had already reached an advanced stage in a majority of the patients. In 26% of cases it was known that complete resection of tumour tissue had not been achieved. A direct relationship between stage of spread and histological grade of malignancy was noted. The incidence of advanced stage, high histological grade and mucinous tumours was greatest in the right side of the colon. A study of early carcinomas has confirmed that many have arisen from benign epithelial neoplastic polyps. The significance of these observations is discussed."} {"id": "PMID:178987", "title": "[Beta-sitosterin in unsuccessfully pretreated patients with hypercholesteremia. Simultaneously, a contribution to dose dependence].", "content": "To 9 patients with hyperlipoproteinemia type II and treated with different hypolipidemic drugs without success, sitosterol was given for a period of 4 to 16 months. The effective dose was 10.56 to 21.12g beta-sitosterol corresponding to 12 to 24g granulate. One patient developed a serious diarrhoe and dropped out. 4 patients showed an impressive decrease of serum cholesterol levels.", "contents": "[Beta-sitosterin in unsuccessfully pretreated patients with hypercholesteremia. Simultaneously, a contribution to dose dependence]. To 9 patients with hyperlipoproteinemia type II and treated with different hypolipidemic drugs without success, sitosterol was given for a period of 4 to 16 months. The effective dose was 10.56 to 21.12g beta-sitosterol corresponding to 12 to 24g granulate. One patient developed a serious diarrhoe and dropped out. 4 patients showed an impressive decrease of serum cholesterol levels."} {"id": "PMID:178991", "title": "The role of cAMP in flagellation of Salmonella typhimurium.", "content": "A mutational alteration either in adenylate cyclase (cya-) or in cyclic-3'5'-AMP (cAMP) receptor protein (crp-) rendered Salmonella typhimurium incapable of producing flagella. The amount of mRNA specific for flagellin in these mutants was almost negligible when assayed in an in vitro protein synthesizing system. A secondary mutation cfs, partially suppressing the cya- mutation, was identified among the revertants of cya-. A mutation in the same cistron as cfs resulted in a non-flagellate phenotype either by itself or in combination with cfs. The cistron, which was given the gene symbol flaT, was located between flaE and flaL. It was suggested that cAMP receptor protein together with cAMP modulates the gene flaT, which in turn acts as a positive effector on the synthesis of active mRNA specific for flagellin.", "contents": "The role of cAMP in flagellation of Salmonella typhimurium. A mutational alteration either in adenylate cyclase (cya-) or in cyclic-3'5'-AMP (cAMP) receptor protein (crp-) rendered Salmonella typhimurium incapable of producing flagella. The amount of mRNA specific for flagellin in these mutants was almost negligible when assayed in an in vitro protein synthesizing system. A secondary mutation cfs, partially suppressing the cya- mutation, was identified among the revertants of cya-. A mutation in the same cistron as cfs resulted in a non-flagellate phenotype either by itself or in combination with cfs. The cistron, which was given the gene symbol flaT, was located between flaE and flaL. It was suggested that cAMP receptor protein together with cAMP modulates the gene flaT, which in turn acts as a positive effector on the synthesis of active mRNA specific for flagellin."} {"id": "PMID:178993", "title": "Characterization of an adenovirus early protein required for viral DNA replication: a single strand specific DNA binding proteins.", "content": "1. The human adenoviruses types 2, 5 and 12 code for the production of a single strand specific DNA binding protein. The molecular weights of these proteins were 72,000 for types 2 and 5 and 60,000 for type 12. In all three cases proteolytic breakdown fragments of these binding proteins (48,000 MW) were also observed. 2. Analysis of the methionine containing tryptic peptides of these proteins indicate that the types 2 and 5 proteins are similar and clearly distinguishable from the type 12 protein. The peptide maps of these three viral proteins are clearly different from a similar protein found in mock infected cells. 3. Temperature sensitive mutants of type 5 (H5ts125) and type 12(H12tsA275) adenoviruses fail to produce these proteins at the nonpermissive temperature. H5ts125 infected cells grown at the permissive temperature produce a 72,000 MW protein that is thermolabile, for continued binding to DNA, when compared to type 5 wild type adenovirus 72,000 MW protein. An analysis of the phenotype of this adenovirus mutant indicates that it codes for a viral function at early times after infection that is required for viral DNA replication. 4. The in vitro translation of adenovirus specific m-RNA results in the synthesis of a small amount of a 72,000 MW protein that binds to single stranded DNA just like the authentic adenovirus DNA binding proteins produced in infected cells. 5. Adenovirus anti-Tumor antigen (T) anti-serum from hamsters carrying independently derived adenovirus tumors, have been tested for the presence of antibody to purified DNA binding proteins. One antiserum is positive for these antibodies while the other is negative. These results indicate that some, but not all, adenovirus tumors contain large enough levels of the DNA binding proteins to elicit an antibody response. 6. The type 5 adenovirus temperature sensitive mutant, H5ts125, that codes for a thermolabile DNA binding protein, was complemented or suppressed at the nonpermissive temperature, for the replication of adenovirus DNA, by SV40. SV40tsA temperature sensitive mutants, defective in SV40 DNA replication, do not suppress or complement H5ts125 at the nonpermissive temperature.", "contents": "Characterization of an adenovirus early protein required for viral DNA replication: a single strand specific DNA binding proteins. 1. The human adenoviruses types 2, 5 and 12 code for the production of a single strand specific DNA binding protein. The molecular weights of these proteins were 72,000 for types 2 and 5 and 60,000 for type 12. In all three cases proteolytic breakdown fragments of these binding proteins (48,000 MW) were also observed. 2. Analysis of the methionine containing tryptic peptides of these proteins indicate that the types 2 and 5 proteins are similar and clearly distinguishable from the type 12 protein. The peptide maps of these three viral proteins are clearly different from a similar protein found in mock infected cells. 3. Temperature sensitive mutants of type 5 (H5ts125) and type 12(H12tsA275) adenoviruses fail to produce these proteins at the nonpermissive temperature. H5ts125 infected cells grown at the permissive temperature produce a 72,000 MW protein that is thermolabile, for continued binding to DNA, when compared to type 5 wild type adenovirus 72,000 MW protein. An analysis of the phenotype of this adenovirus mutant indicates that it codes for a viral function at early times after infection that is required for viral DNA replication. 4. The in vitro translation of adenovirus specific m-RNA results in the synthesis of a small amount of a 72,000 MW protein that binds to single stranded DNA just like the authentic adenovirus DNA binding proteins produced in infected cells. 5. Adenovirus anti-Tumor antigen (T) anti-serum from hamsters carrying independently derived adenovirus tumors, have been tested for the presence of antibody to purified DNA binding proteins. One antiserum is positive for these antibodies while the other is negative. These results indicate that some, but not all, adenovirus tumors contain large enough levels of the DNA binding proteins to elicit an antibody response. 6. The type 5 adenovirus temperature sensitive mutant, H5ts125, that codes for a thermolabile DNA binding protein, was complemented or suppressed at the nonpermissive temperature, for the replication of adenovirus DNA, by SV40. SV40tsA temperature sensitive mutants, defective in SV40 DNA replication, do not suppress or complement H5ts125 at the nonpermissive temperature."} {"id": "PMID:178994", "title": "[Plasma fibrinogen activity in diabetes mellitus, hyperlipoproteinemia and hyperuricemia (author's transl)].", "content": "Plasma fibrinogen content was measured in 20 normal subjects, 20 patients with diabetes mellitus, 20 patients with hyperlipoproteinemia type II or IV (Fredrickson) and 10 patients with hyperuricemia. These vascular risks were accompanied by significant increase of plasma fibrinogen in comparison with the normal collective. The highest fibrinogen concentrations were found in diabetics, followed by hyperuricemias and hyperlipoproteinemias. The importance of coagulation disturbances is discussed in regard of angiopathogenesis.", "contents": "[Plasma fibrinogen activity in diabetes mellitus, hyperlipoproteinemia and hyperuricemia (author's transl)]. Plasma fibrinogen content was measured in 20 normal subjects, 20 patients with diabetes mellitus, 20 patients with hyperlipoproteinemia type II or IV (Fredrickson) and 10 patients with hyperuricemia. These vascular risks were accompanied by significant increase of plasma fibrinogen in comparison with the normal collective. The highest fibrinogen concentrations were found in diabetics, followed by hyperuricemias and hyperlipoproteinemias. The importance of coagulation disturbances is discussed in regard of angiopathogenesis."} {"id": "PMID:178995", "title": "[Immunosuppression and endogenic viral reinfection (author's transl)].", "content": "The consequence of nonspecific immunosuppressive therapy is a more frequent appearance of virus infections in the patients. They are largely caused by herpes and papova viruses. In addition to primary and recurrent exogenous infections, endogenous reinfections also have great importance. Clinically there is a broad palette from severe to inapparent types of infection. The use of live virus vaccines is contraindicated during immunosuppressive therapy.", "contents": "[Immunosuppression and endogenic viral reinfection (author's transl)]. The consequence of nonspecific immunosuppressive therapy is a more frequent appearance of virus infections in the patients. They are largely caused by herpes and papova viruses. In addition to primary and recurrent exogenous infections, endogenous reinfections also have great importance. Clinically there is a broad palette from severe to inapparent types of infection. The use of live virus vaccines is contraindicated during immunosuppressive therapy."} {"id": "PMID:178997", "title": "Linear dose--response relationships after prolonged expression times in V-79 Chinese hamster cells.", "content": "The expression time for induced mutants resistant to 6-thioguanine, in V-79 Chinese hamster cells, was determined by respreading the cells in the selective medium, at various times after treatment. The length of the expression time for mutants induced by X-rays, ethyl methane sulphonate and ultraviolet irradiation was dose dependent. For the highest dose used this was 7 to 8 days, beyond which there was no further changes in mutant frequency. The dose-response relationship of these agents does not appear to deviate from linearity; this permits the calculation of mutation rate per unit dose. For X-rays this value was 1.35 - 10(-7) per rad per locus, for ethyl methane sulphonate, 2.2 - 10(-2) per mole per locus and for ultraviolet irradiation, 6.3 - 10(-6) per erg per mm2 per locus. The effectiveness of the 3 different mutagens for the induction of mutations was compared by calculating the increase in mutant frequency per unit of decrease in survival (Do). These increments in frequency were: 5.6 - 10(-5) for X-rays, 69.5 - 10(-5) for ethyl methane sulphonate and 16.1 - 10(-5) for ultraviolet irradiation.", "contents": "Linear dose--response relationships after prolonged expression times in V-79 Chinese hamster cells. The expression time for induced mutants resistant to 6-thioguanine, in V-79 Chinese hamster cells, was determined by respreading the cells in the selective medium, at various times after treatment. The length of the expression time for mutants induced by X-rays, ethyl methane sulphonate and ultraviolet irradiation was dose dependent. For the highest dose used this was 7 to 8 days, beyond which there was no further changes in mutant frequency. The dose-response relationship of these agents does not appear to deviate from linearity; this permits the calculation of mutation rate per unit dose. For X-rays this value was 1.35 - 10(-7) per rad per locus, for ethyl methane sulphonate, 2.2 - 10(-2) per mole per locus and for ultraviolet irradiation, 6.3 - 10(-6) per erg per mm2 per locus. The effectiveness of the 3 different mutagens for the induction of mutations was compared by calculating the increase in mutant frequency per unit of decrease in survival (Do). These increments in frequency were: 5.6 - 10(-5) for X-rays, 69.5 - 10(-5) for ethyl methane sulphonate and 16.1 - 10(-5) for ultraviolet irradiation."} {"id": "PMID:178998", "title": "Host-cell reactivation of ultraviolet-irradiated SV40 DNA in five complementation groups of xeroderma pigmentosum.", "content": "Host-cell reactivation of UV-irradiated double-stranded SV40 DNA was studied in BSC-1 monkey cells, normal human cells, heterozygous Xeroderma pigmentosum (XP) cells, representative cell strains of the five complemention groups of XP and in XP \"variant\" cells. The following percentages of survival of the plaque-forming ability of double-stranded SV40 DNA were found in XP cells compared with the value found in normal monkey and human cells: group A, 13%; group B, 30%; group C, 18%; group D, 14%; group E, 59%; and in the heterozygous XP cells almost 100%. The survival in XP \"variant\" cells was 66%. The survival of single-stranded SV40 DNA in BSC-1 cells was much lower than that of double-stranded SV40 DNA in XP cells of complementation group A, which possibly indicates that some repair of UV damage occurs even in XP cells of group A.", "contents": "Host-cell reactivation of ultraviolet-irradiated SV40 DNA in five complementation groups of xeroderma pigmentosum. Host-cell reactivation of UV-irradiated double-stranded SV40 DNA was studied in BSC-1 monkey cells, normal human cells, heterozygous Xeroderma pigmentosum (XP) cells, representative cell strains of the five complemention groups of XP and in XP \"variant\" cells. The following percentages of survival of the plaque-forming ability of double-stranded SV40 DNA were found in XP cells compared with the value found in normal monkey and human cells: group A, 13%; group B, 30%; group C, 18%; group D, 14%; group E, 59%; and in the heterozygous XP cells almost 100%. The survival in XP \"variant\" cells was 66%. The survival of single-stranded SV40 DNA in BSC-1 cells was much lower than that of double-stranded SV40 DNA in XP cells of complementation group A, which possibly indicates that some repair of UV damage occurs even in XP cells of group A."} {"id": "PMID:178999", "title": "Formaldehyde-induced hemolysis during chronic hemodialysis.", "content": "We investigated an outbreak of hemolytic anemia among patients on hemodialysis shortly after the installation of a new water-filtration system. Using in vitro technics, we demonstrated that a water-soluble inhibitor of red-cell metabolism could easily be extracted from the intact filters. Subsequent experiments showed this toxic substance to be formaldehyde, a potent reducing agent whose mechanism of action involves conversion of NAD to NADH. This alteration of the redox state of the erythrocyte leads to inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase and rapid decline in cellular energy (ATP) stores. Because formaldehyde is widely used as a preservative for dialysis equipment, the toxicity of this agent for red blood cells is of clinical importance.", "contents": "Formaldehyde-induced hemolysis during chronic hemodialysis. We investigated an outbreak of hemolytic anemia among patients on hemodialysis shortly after the installation of a new water-filtration system. Using in vitro technics, we demonstrated that a water-soluble inhibitor of red-cell metabolism could easily be extracted from the intact filters. Subsequent experiments showed this toxic substance to be formaldehyde, a potent reducing agent whose mechanism of action involves conversion of NAD to NADH. This alteration of the redox state of the erythrocyte leads to inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase and rapid decline in cellular energy (ATP) stores. Because formaldehyde is widely used as a preservative for dialysis equipment, the toxicity of this agent for red blood cells is of clinical importance."} {"id": "PMID:179005", "title": "Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia.", "content": "Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle.", "contents": "Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia. Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle."} {"id": "PMID:179007", "title": "[Relation between quality of dietary protein, plasma corticosteroid concentration and various enzyme activities in liver and mucosa of small intestine].", "content": "Comprehensive studies were performed in Wistar rats on the relations between the dietary protein quality and the function of the adrenocortical system. The authors determined: the increase in body mass, the urea and corticosteroid concentrations in the blood plasma, the GOT (EC 2.6.I.I.) and GPT (EC 2.6.I.2.) activities in the liver, the reactivity of the adrenocortical system in vitro, the ACTH content in the hypophyses and the content of corticosteroid-binding globulin in the blood plasma. In adrenalectomized and normal rats as well as in rats treated with corticosterone or cortisol, the authors determined the GPT, GOT, amino-acid aryl amidase (EC 3.4.I.2.) and tripeptidase (EC 3.4.I.3.) activities in the liver and the mucosa of the small intestine, and the total, alpha and beta-amylase activities in the small intestine.", "contents": "[Relation between quality of dietary protein, plasma corticosteroid concentration and various enzyme activities in liver and mucosa of small intestine]. Comprehensive studies were performed in Wistar rats on the relations between the dietary protein quality and the function of the adrenocortical system. The authors determined: the increase in body mass, the urea and corticosteroid concentrations in the blood plasma, the GOT (EC 2.6.I.I.) and GPT (EC 2.6.I.2.) activities in the liver, the reactivity of the adrenocortical system in vitro, the ACTH content in the hypophyses and the content of corticosteroid-binding globulin in the blood plasma. In adrenalectomized and normal rats as well as in rats treated with corticosterone or cortisol, the authors determined the GPT, GOT, amino-acid aryl amidase (EC 3.4.I.2.) and tripeptidase (EC 3.4.I.3.) activities in the liver and the mucosa of the small intestine, and the total, alpha and beta-amylase activities in the small intestine."} {"id": "PMID:179008", "title": "Production of yeast alcohol dehydrogenase isoenzymes by selection.", "content": "Mutants of yeast alcohol dehydrogenase have been produced that protect the cell against the poisonous aldehyde acrolein by increasing the NADH-NAD ratio. The altered properties include changes both in binding constants and in cooperativity. Such mutants may be useful in exploring the nature of adaptation at the molecular level.", "contents": "Production of yeast alcohol dehydrogenase isoenzymes by selection. Mutants of yeast alcohol dehydrogenase have been produced that protect the cell against the poisonous aldehyde acrolein by increasing the NADH-NAD ratio. The altered properties include changes both in binding constants and in cooperativity. Such mutants may be useful in exploring the nature of adaptation at the molecular level."} {"id": "PMID:179013", "title": "Evolution of type C viral genes: evidence for an Asian origin of man.", "content": "Old World monkeys and apes, including man, possess, as a normal component of their cellular DNA, gene sequences (virogenes) related to the RNA of a virus isolated from baboons. A comparison of the viral gene sequences and the other cellular sequences distinguishes those Old World monkeys and apes that have evolved in Africa from those that have evolved in Asia. Among the apes, only gorilla and chimpanzee seem by these criteria to be African, whereas gibbon, orang-utan and man are identified as Asian, leading us to conclude that most of man's evolution has occurred outside Africa.", "contents": "Evolution of type C viral genes: evidence for an Asian origin of man. Old World monkeys and apes, including man, possess, as a normal component of their cellular DNA, gene sequences (virogenes) related to the RNA of a virus isolated from baboons. A comparison of the viral gene sequences and the other cellular sequences distinguishes those Old World monkeys and apes that have evolved in Africa from those that have evolved in Asia. Among the apes, only gorilla and chimpanzee seem by these criteria to be African, whereas gibbon, orang-utan and man are identified as Asian, leading us to conclude that most of man's evolution has occurred outside Africa."} {"id": "PMID:179017", "title": "Cell-cycle, cell-shape mutant with features of the Go state.", "content": "A cold-sensitive mutant of CHO cells has features of \"reverse transformation\" at the non-premissive temperature of 33 degrees C. Cells accumulate at G1 with altered morphology and remain viable and quiescent for more than 40 d. Such cultures are synchronised by a temperature shift back to the permissive 39 degrees C.", "contents": "Cell-cycle, cell-shape mutant with features of the Go state. A cold-sensitive mutant of CHO cells has features of \"reverse transformation\" at the non-premissive temperature of 33 degrees C. Cells accumulate at G1 with altered morphology and remain viable and quiescent for more than 40 d. Such cultures are synchronised by a temperature shift back to the permissive 39 degrees C."} {"id": "PMID:179023", "title": "[Synchronization of the background activity of skeletal musculature, autonomic nerves and cerebral structures in cats].", "content": "The background electrical activity of skeletal muscles, autonomic nerves and several brain structures was recorded in cats under acute and chronic conditions. The spectrum-correlation analysis showed that the spatial synchronization within the range of 25 to 35 Hz between autonomic nerves and brain formations (established in previous experiments) comprises the skeletal muscles as well. One of the possible mechanisms by which the rhythm of 25 to 35 Hz facilitates activity in the nervous system is suggested to be related to the frequency potentiation of the synaptic transmission.", "contents": "[Synchronization of the background activity of skeletal musculature, autonomic nerves and cerebral structures in cats]. The background electrical activity of skeletal muscles, autonomic nerves and several brain structures was recorded in cats under acute and chronic conditions. The spectrum-correlation analysis showed that the spatial synchronization within the range of 25 to 35 Hz between autonomic nerves and brain formations (established in previous experiments) comprises the skeletal muscles as well. One of the possible mechanisms by which the rhythm of 25 to 35 Hz facilitates activity in the nervous system is suggested to be related to the frequency potentiation of the synaptic transmission."} {"id": "PMID:179027", "title": "[Endocrinological evaluation of sellar and suprasellar tumor cases (author's transl)].", "content": "1) Pituitary function of 9 cases of tuberculum sellae meningioma was examined, before and after surgery (3 weeks, 1 year and 2 years after surgery). 2) In all cases ACTH, LH, FSH and prolactin responses were normal throughout pre- and postoperative courses. 3) GH and TSH were normoreactive in almost all cases preoperatively. Postoperatively GH and TSH were hyporeactive 3 weeks after surgery, but recovered to normal 1 or 2 years after surgery.", "contents": "[Endocrinological evaluation of sellar and suprasellar tumor cases (author's transl)]. 1) Pituitary function of 9 cases of tuberculum sellae meningioma was examined, before and after surgery (3 weeks, 1 year and 2 years after surgery). 2) In all cases ACTH, LH, FSH and prolactin responses were normal throughout pre- and postoperative courses. 3) GH and TSH were normoreactive in almost all cases preoperatively. Postoperatively GH and TSH were hyporeactive 3 weeks after surgery, but recovered to normal 1 or 2 years after surgery."} {"id": "PMID:179028", "title": "[Endocrinological evaluation of sellar and suprasellar tumor cases (the fifth report) - on pituitary function of 5 cases of ectopic pinealoma in the Chiasmal Region (author's transl)].", "content": "The anterior pituitary hormone secretion of 5 patients with ectopic pinealoma in the chiasmal region was studied. 1) GH response in ITT was hyporeactive in all cases. Two of 4 cases showed hyporeactive ACTH secretion in Metyrapone test. Two of 5 cases decreased TSH secretion in TRH test. Prolaction secretion was normal in all 5 cases. All 5 cases showed hyporeactive FHS response. LH secretion was negligible in 2 of 5 cases, but other 3 cases showed abnormal LH response in LH0RH test with abnormally high basal level and no response to LH-RH. 2) In 3 cases with abnormal LH response blood HCG was determined and identified by radio-immuno-assay using HCG-beta-subunit antiserum. 3) Precocious puberty was recognized in 2 boys with identified blood HCG. 4) Abnormally high blood LH levels in those 3 cases were significantly decreased after lineac irraiation.", "contents": "[Endocrinological evaluation of sellar and suprasellar tumor cases (the fifth report) - on pituitary function of 5 cases of ectopic pinealoma in the Chiasmal Region (author's transl)]. The anterior pituitary hormone secretion of 5 patients with ectopic pinealoma in the chiasmal region was studied. 1) GH response in ITT was hyporeactive in all cases. Two of 4 cases showed hyporeactive ACTH secretion in Metyrapone test. Two of 5 cases decreased TSH secretion in TRH test. Prolaction secretion was normal in all 5 cases. All 5 cases showed hyporeactive FHS response. LH secretion was negligible in 2 of 5 cases, but other 3 cases showed abnormal LH response in LH0RH test with abnormally high basal level and no response to LH-RH. 2) In 3 cases with abnormal LH response blood HCG was determined and identified by radio-immuno-assay using HCG-beta-subunit antiserum. 3) Precocious puberty was recognized in 2 boys with identified blood HCG. 4) Abnormally high blood LH levels in those 3 cases were significantly decreased after lineac irraiation."} {"id": "PMID:179029", "title": "CRF activity in fetal rat hypothalamus, in late pregnancy.", "content": "The corticosterone content of the adrenal glands was determined in 21-day-old rat fetuses: (1) before and after encephalectomy or decapitation (hypophysectomy); (2) after ACTH treatment of the encephalectomized or decapitated (hypophysectomized) fetuses; and (3) after administration of crude extracts (0.1 N HCl) of hypothalamic or cortical tissue from 20-day-old rat fetuses. A peak in the corticosterone content of the adrenals was observed 10 min after ACTH injection to enceaphlectomized or decapitated fetuses. A rise in corticosterone concentration was noted 5 and 10 min after the encephalectomized fetuses were given an injection of hypothalamic extract. This extract was devoid of appreciable ACTH activity when tested in decapitated fetuses. Cortical extract was inactive in encephalectomized or decapitated fetuses. These data suggest that fetal hypothalamic extract contains some CRF activity and that the fetal pituitary gland is responsive to the CRF.", "contents": "CRF activity in fetal rat hypothalamus, in late pregnancy. The corticosterone content of the adrenal glands was determined in 21-day-old rat fetuses: (1) before and after encephalectomy or decapitation (hypophysectomy); (2) after ACTH treatment of the encephalectomized or decapitated (hypophysectomized) fetuses; and (3) after administration of crude extracts (0.1 N HCl) of hypothalamic or cortical tissue from 20-day-old rat fetuses. A peak in the corticosterone content of the adrenals was observed 10 min after ACTH injection to enceaphlectomized or decapitated fetuses. A rise in corticosterone concentration was noted 5 and 10 min after the encephalectomized fetuses were given an injection of hypothalamic extract. This extract was devoid of appreciable ACTH activity when tested in decapitated fetuses. Cortical extract was inactive in encephalectomized or decapitated fetuses. These data suggest that fetal hypothalamic extract contains some CRF activity and that the fetal pituitary gland is responsive to the CRF."} {"id": "PMID:179030", "title": "Effects of carbohydrate-active steroids and ACTH on visually-evoked responses in patients with adrenal cortical insufficiency.", "content": "Visual average evoked responses (AERs) to 4 intensities of light were studied in 5 patients with adrenal cortical insufficiency. Patients were tested off all medications, on ACTH while off all medications, and during replacement with carbohydrate-active steroids. Off treatment, when steroid levels were low, AERs were of small amplitude and short latency. Treatment with ACTH alone decreased the amplitude-intensity response, suggesting extra-adrenal effects. Both with amplitude and latency effects, stimulus intensity was an important parameter in determining steroid and ACTH effects.", "contents": "Effects of carbohydrate-active steroids and ACTH on visually-evoked responses in patients with adrenal cortical insufficiency. Visual average evoked responses (AERs) to 4 intensities of light were studied in 5 patients with adrenal cortical insufficiency. Patients were tested off all medications, on ACTH while off all medications, and during replacement with carbohydrate-active steroids. Off treatment, when steroid levels were low, AERs were of small amplitude and short latency. Treatment with ACTH alone decreased the amplitude-intensity response, suggesting extra-adrenal effects. Both with amplitude and latency effects, stimulus intensity was an important parameter in determining steroid and ACTH effects."} {"id": "PMID:179037", "title": "White sponge nevus (leukoedema exfoliativum mucosae oris): ultrastructural observations.", "content": "Biopsy specimens from the oral lesions of white sponge nevus (WSN) in thirteen patients were analyzed by electron microscopy. Several marked deviations from the normal ultrastructure were recorded. Similarities and dissimilarities with other hereditary disturbances affecting the epithelium are discussed. Profound disturbance of the tonofilament system, with atypical aggregation of tonofilaments, was observed. Odland bodies, which are numerous in keratinized epithelia and are extruded into the intercellular space prior to the exfoliation of the surface cells, were also abundant in the WSN specimens. Very little material originating from Odland bodies appears, however, in the intercellular space in WSN. Presumably, the Odland bodies fail to properly function enzymatically in WSN.", "contents": "White sponge nevus (leukoedema exfoliativum mucosae oris): ultrastructural observations. Biopsy specimens from the oral lesions of white sponge nevus (WSN) in thirteen patients were analyzed by electron microscopy. Several marked deviations from the normal ultrastructure were recorded. Similarities and dissimilarities with other hereditary disturbances affecting the epithelium are discussed. Profound disturbance of the tonofilament system, with atypical aggregation of tonofilaments, was observed. Odland bodies, which are numerous in keratinized epithelia and are extruded into the intercellular space prior to the exfoliation of the surface cells, were also abundant in the WSN specimens. Very little material originating from Odland bodies appears, however, in the intercellular space in WSN. Presumably, the Odland bodies fail to properly function enzymatically in WSN."} {"id": "PMID:179038", "title": "Multifocal adenoid cystic carcinoma of the lip.", "content": "A 62-year-old Caucasian woman had several distinct and separate adenoid cystic carcinomas which involved both sides of the upper lip. Microscopic examination of the surgical specimens suggested that at least one of these malignant neoplasms arose from a pre-existing basal-cell adenoma.", "contents": "Multifocal adenoid cystic carcinoma of the lip. A 62-year-old Caucasian woman had several distinct and separate adenoid cystic carcinomas which involved both sides of the upper lip. Microscopic examination of the surgical specimens suggested that at least one of these malignant neoplasms arose from a pre-existing basal-cell adenoma."} {"id": "PMID:179041", "title": "[Definition and significance of carcinoma in situ of the breast gland].", "content": "1. Preinvasive phases of the cancer of the breast are observed with the intraductal cancers of the bigger ducts and with the so-called lobular carcinoma in situ. It shows, however, that the carcinoma of the ducts, above all the comedo-carcinoma, have to be considered as invasive cancers in more than 75%. These forms extend to the lobuli of the breast. 2. The Morbus Paget bases in one third on an intraductal preinvasive carcinoma, in two thirds on an invasive cancer. 3. This chapter deals with the differential diagnosis of the papilloma and papillary carcinoma. 4. Intralobular proliferations of the epithelium are observed at the periphery of undifferentiated cancers as secondary intraductal carcinoma and as primary lobular carcinoma. The so-called intralobular carcinoma in situ is in 15,2% followed by an invasive carcinoma after an interval of up to 28 years, and in 23% ipsilateral, in 9,5% contralateral. As therapy the subcutaneous or simple mastectomy is proposed.", "contents": "[Definition and significance of carcinoma in situ of the breast gland]. 1. Preinvasive phases of the cancer of the breast are observed with the intraductal cancers of the bigger ducts and with the so-called lobular carcinoma in situ. It shows, however, that the carcinoma of the ducts, above all the comedo-carcinoma, have to be considered as invasive cancers in more than 75%. These forms extend to the lobuli of the breast. 2. The Morbus Paget bases in one third on an intraductal preinvasive carcinoma, in two thirds on an invasive cancer. 3. This chapter deals with the differential diagnosis of the papilloma and papillary carcinoma. 4. Intralobular proliferations of the epithelium are observed at the periphery of undifferentiated cancers as secondary intraductal carcinoma and as primary lobular carcinoma. The so-called intralobular carcinoma in situ is in 15,2% followed by an invasive carcinoma after an interval of up to 28 years, and in 23% ipsilateral, in 9,5% contralateral. As therapy the subcutaneous or simple mastectomy is proposed."} {"id": "PMID:179042", "title": "[Pathological and anatomical aspects of organ-preserving therapy in the early stages of breast cancer].", "content": "In the treatment of breast cancer a worldwide trent towards selective and more individualized methods can be observed. Selective treatment depends to a considerable extend on precise morphological diagnosis. Conservative surgery combined with radiotherapy seems to be justified in cases of smallsized carcinomas of stage T0, N0, M0, and T1, N0, M0. There are different opinions on the adequate treatment of non-infiltrating carcinomas (i.e. intraductal comedo carcinoma, non-infiltrating lobular carcinoma). Up till now standard methods are not applicable. The high frequency of multicentric and bilateral development, and the unfavorable mode of segmental canalicular outgrowth are critical factors that must be taken into consideration for individual therapeutic planning.", "contents": "[Pathological and anatomical aspects of organ-preserving therapy in the early stages of breast cancer]. In the treatment of breast cancer a worldwide trent towards selective and more individualized methods can be observed. Selective treatment depends to a considerable extend on precise morphological diagnosis. Conservative surgery combined with radiotherapy seems to be justified in cases of smallsized carcinomas of stage T0, N0, M0, and T1, N0, M0. There are different opinions on the adequate treatment of non-infiltrating carcinomas (i.e. intraductal comedo carcinoma, non-infiltrating lobular carcinoma). Up till now standard methods are not applicable. The high frequency of multicentric and bilateral development, and the unfavorable mode of segmental canalicular outgrowth are critical factors that must be taken into consideration for individual therapeutic planning."} {"id": "PMID:179043", "title": "[Multicentric carcinoma and atypical hyperplasia of the mammary gland (author's transl)].", "content": "A study for multiple primary cancer in the female mammary gland was performed. In 145 cases of mammary cancer, blocks for histological analysis were taken in a special system following routine examination of the specimen. Three sagital sections each of one inch width were taken from the outer, medium and inner region and from each of these 6 small blocks were cut. By this constant pattern of histological screening, 9 cases out of 145 were found showing multiple primary cancers. Among these Carcinoma solidum scirrhosum was the most frequent tumor type. This percentage of 6.2 is considerably lower than that given in the pertinent literature. Residual cancer following biopsy was found in 81% of the 145 cases, although extensive excision had been tried by the first operation. The entity of atypical epithelial hyperplasia which has to be differentiated from Carcinoma in situ was observed in 40.5% including ductal and ductular system.", "contents": "[Multicentric carcinoma and atypical hyperplasia of the mammary gland (author's transl)]. A study for multiple primary cancer in the female mammary gland was performed. In 145 cases of mammary cancer, blocks for histological analysis were taken in a special system following routine examination of the specimen. Three sagital sections each of one inch width were taken from the outer, medium and inner region and from each of these 6 small blocks were cut. By this constant pattern of histological screening, 9 cases out of 145 were found showing multiple primary cancers. Among these Carcinoma solidum scirrhosum was the most frequent tumor type. This percentage of 6.2 is considerably lower than that given in the pertinent literature. Residual cancer following biopsy was found in 81% of the 145 cases, although extensive excision had been tried by the first operation. The entity of atypical epithelial hyperplasia which has to be differentiated from Carcinoma in situ was observed in 40.5% including ductal and ductular system."} {"id": "PMID:179044", "title": "[Virus infections in man during immunodepression (author's transl)].", "content": "The authors review virus infections observed in patients undergoing immunosuppressive treatment. The herpes virus, in particular the cytomegalovirus, are the most important cause. However, the role of the virus itself in an unfavourable course is variously assessed. The mechanism of the virus infection is discussed, whether primary infection, exogenous or endogenous re-infection. The latter seems to be the most frequent, at least in the case of the herpes viruses.", "contents": "[Virus infections in man during immunodepression (author's transl)]. The authors review virus infections observed in patients undergoing immunosuppressive treatment. The herpes virus, in particular the cytomegalovirus, are the most important cause. However, the role of the virus itself in an unfavourable course is variously assessed. The mechanism of the virus infection is discussed, whether primary infection, exogenous or endogenous re-infection. The latter seems to be the most frequent, at least in the case of the herpes viruses."} {"id": "PMID:179045", "title": "Influence of age and sex on carcinoma and cirrhosis of the liver in AXC strain rats ingesting 0.025% N-2-fluorenyldiacetamide.", "content": "Inbred A X C male and female rats, 4, 12, 24, and 52 weeks of age, ingested 0.025% N-2-fluorenyldiacetamide in a semisynthetic diet. Both age and sex were important in the development of hepatic lesions. The 4- and 12-week-old males developed a higher incidence of carcinomas and cirrhosis of the liver than did the females of the same ages or the males and females 24 and 52 weeks of age. Four-week-old male rats had more carcinomas per liver, larger carcinomas, more poorly differentiated (as compared with well differentiated), and some carcinomas were cholangiocellular as well as hepatocellular. There were a few hepatic lesions in the younger female rats; however, female rats of all ages were relatively resistant to hepatic carcinogenesis.", "contents": "Influence of age and sex on carcinoma and cirrhosis of the liver in AXC strain rats ingesting 0.025% N-2-fluorenyldiacetamide. Inbred A X C male and female rats, 4, 12, 24, and 52 weeks of age, ingested 0.025% N-2-fluorenyldiacetamide in a semisynthetic diet. Both age and sex were important in the development of hepatic lesions. The 4- and 12-week-old males developed a higher incidence of carcinomas and cirrhosis of the liver than did the females of the same ages or the males and females 24 and 52 weeks of age. Four-week-old male rats had more carcinomas per liver, larger carcinomas, more poorly differentiated (as compared with well differentiated), and some carcinomas were cholangiocellular as well as hepatocellular. There were a few hepatic lesions in the younger female rats; however, female rats of all ages were relatively resistant to hepatic carcinogenesis."} {"id": "PMID:179050", "title": "Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs.", "content": "Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3).", "contents": "Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs. Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3)."} {"id": "PMID:179054", "title": "Effect of two experimental sets on sleep structure.", "content": "The effect of four perceptual sets--First Night in a sleep laboratory, Second Night in a sleep laboratory, Shock Avoidance Night, Reward Night--on the distribution of sleep was examined with 12Ss. Both the shock avoidance and the reward conditions gave results similar to those characteristically found in the First Night Effect, i.e., increases in Stage 0, Stage 1, the latency to Stage 4, the number of Awakenings, and the number of Stage Changes coupled with a decrease in Stage 1-REM. The observed effects, however, were minimal and were interpreted as giving evidence for the sturdiness of the sleep process.", "contents": "Effect of two experimental sets on sleep structure. The effect of four perceptual sets--First Night in a sleep laboratory, Second Night in a sleep laboratory, Shock Avoidance Night, Reward Night--on the distribution of sleep was examined with 12Ss. Both the shock avoidance and the reward conditions gave results similar to those characteristically found in the First Night Effect, i.e., increases in Stage 0, Stage 1, the latency to Stage 4, the number of Awakenings, and the number of Stage Changes coupled with a decrease in Stage 1-REM. The observed effects, however, were minimal and were interpreted as giving evidence for the sturdiness of the sleep process."} {"id": "PMID:179056", "title": "[Total vascular exclusion of the liver in extensive hepatic exeresis. Value and limits].", "content": "Three cases of right hepatic lobectomy performed under complete hepatic vascular exclusion with aortic clamping in normothermia are reported. Hemostasis of the row surface of the liver is obtained with application of a biological glue. Hepatic vascular exclusion (from 24 to 30mn) was harmless to the remnant liver and the kidneys. Blood loss was minimal. The hemodynamic tolerance was good all along the procedure, but there is a high risk of overloading and acute congestive heart failure immediately after removal of the clamps. The continuous monitoring of pulmonary artery pressures must be emphasized. This procedure may be advised for massive and hypervascular tumors of the right lobe of the liver.", "contents": "[Total vascular exclusion of the liver in extensive hepatic exeresis. Value and limits]. Three cases of right hepatic lobectomy performed under complete hepatic vascular exclusion with aortic clamping in normothermia are reported. Hemostasis of the row surface of the liver is obtained with application of a biological glue. Hepatic vascular exclusion (from 24 to 30mn) was harmless to the remnant liver and the kidneys. Blood loss was minimal. The hemodynamic tolerance was good all along the procedure, but there is a high risk of overloading and acute congestive heart failure immediately after removal of the clamps. The continuous monitoring of pulmonary artery pressures must be emphasized. This procedure may be advised for massive and hypervascular tumors of the right lobe of the liver."} {"id": "PMID:179058", "title": "Electrophoretic analysis of covalently closed SV40 DNA: Boltzmann distributions of DNA species.", "content": "Covalently closed relaxed SV40 DNA [SV40(I')] generated by polynucleotide ligase closure of nicked circular SV40 DNA was analyzed by agarose gel electrophoresis. The DNA can be resolved into a series of bands differing in superhelical density whose intensities are approximately symmetrical about a central most intense band. Densitometric analysis of the gel pattern has revealed that the distribution of DNA species conforms to a Boltzmann distribution and has enabled us to derive an equation for the free energy of superhelix formation for SV40 DNA. We believe the observed bands reflect the time-averaged distribution of thermally induced fluctuations in DNA chain conformation in solution at the time of ligase catalyzed phosphodiester bond formation. Densitometric analysis of native supercoiled SV40 DNA, partially unwound in the presence of ethidium bromide, demonstrates that the separation between adjacent bands is approximately half that seen with SV40(I'). Agarose gel electrophoresis was also used to measure the change in average base rotation angle as a function of temperature by a procedure independent of ethidium dye binding.", "contents": "Electrophoretic analysis of covalently closed SV40 DNA: Boltzmann distributions of DNA species. Covalently closed relaxed SV40 DNA [SV40(I')] generated by polynucleotide ligase closure of nicked circular SV40 DNA was analyzed by agarose gel electrophoresis. The DNA can be resolved into a series of bands differing in superhelical density whose intensities are approximately symmetrical about a central most intense band. Densitometric analysis of the gel pattern has revealed that the distribution of DNA species conforms to a Boltzmann distribution and has enabled us to derive an equation for the free energy of superhelix formation for SV40 DNA. We believe the observed bands reflect the time-averaged distribution of thermally induced fluctuations in DNA chain conformation in solution at the time of ligase catalyzed phosphodiester bond formation. Densitometric analysis of native supercoiled SV40 DNA, partially unwound in the presence of ethidium bromide, demonstrates that the separation between adjacent bands is approximately half that seen with SV40(I'). Agarose gel electrophoresis was also used to measure the change in average base rotation angle as a function of temperature by a procedure independent of ethidium dye binding."} {"id": "PMID:179059", "title": "Isolation and characterization of poly(A)-containing polyoma \"early\" and \"late\" messenger RNAs.", "content": "During late lytic infection of mouse kidney cell cultures polyoma 16S and 19S (late 19S RNA) were isolated by oligo(dT)-cellulose chromatography. Approximately 60-80% of total cytoplasmic polyoma RNA contained tracts of poly(A) which were retained by oligo(dT)-cellulose. Early in lytic infection when viral DNA synthesis and the production of capsid protein are blocked by the addition of 5-fluorodeoxyuridine, approximately 100% of polyoma \"early\" 19S RNA was quantitatively retained by oligo(dT)-cellulose indicating the presence of poly(A) tracts on most 19S mRNA molecules. In addition, 2 classes polyoma RNA, synthesized after the onset of cellular RNA synthesis under conditions where DNA synthesis is inhibited with 5-fluorodeoxyuridine, were found to contain tracts of poly(A). These species sedimenting at 16S and 19S in aqueous sucrose density gradients were also quantitatively retained by oligo (dT)-cellulose.", "contents": "Isolation and characterization of poly(A)-containing polyoma \"early\" and \"late\" messenger RNAs. During late lytic infection of mouse kidney cell cultures polyoma 16S and 19S (late 19S RNA) were isolated by oligo(dT)-cellulose chromatography. Approximately 60-80% of total cytoplasmic polyoma RNA contained tracts of poly(A) which were retained by oligo(dT)-cellulose. Early in lytic infection when viral DNA synthesis and the production of capsid protein are blocked by the addition of 5-fluorodeoxyuridine, approximately 100% of polyoma \"early\" 19S RNA was quantitatively retained by oligo(dT)-cellulose indicating the presence of poly(A) tracts on most 19S mRNA molecules. In addition, 2 classes polyoma RNA, synthesized after the onset of cellular RNA synthesis under conditions where DNA synthesis is inhibited with 5-fluorodeoxyuridine, were found to contain tracts of poly(A). These species sedimenting at 16S and 19S in aqueous sucrose density gradients were also quantitatively retained by oligo (dT)-cellulose."} {"id": "PMID:179060", "title": "Spin labeled nucleic acids.", "content": "Homopolyribonucleotides and E. coli DNA wer spin labeled with an iodoacetamide-nitroxide compound. The extent of labeling is highly dependent upon the nature of the base and the secondary structure of the nucleic acid. This spin label-polymer linkage is unstable at high temperatures and in phosphate buffers. In order to determine the effect of changes in the environment of nucleic acids on the esr signals of their attached spin labels, the polynucleotides were subjected to temperature and viscosity perturbations. An increase in temperature (T) affects a linear decrease in the anisotropy factor of the esr signal. The log tau (tau = correlation time) versus (1/T) profile is linear with a positive slope when the spin label is attached to single stranded polynucleotides but exhibits discontinuities at certain critical temperatures when attached to the duplexes poly (As-U) and poly (I-Cs). These critical temperatures are lower than the optical Tm. Logarithmic increase in viscosity was found to produce a linear increase in tau in aqueous sucrose solutions.", "contents": "Spin labeled nucleic acids. Homopolyribonucleotides and E. coli DNA wer spin labeled with an iodoacetamide-nitroxide compound. The extent of labeling is highly dependent upon the nature of the base and the secondary structure of the nucleic acid. This spin label-polymer linkage is unstable at high temperatures and in phosphate buffers. In order to determine the effect of changes in the environment of nucleic acids on the esr signals of their attached spin labels, the polynucleotides were subjected to temperature and viscosity perturbations. An increase in temperature (T) affects a linear decrease in the anisotropy factor of the esr signal. The log tau (tau = correlation time) versus (1/T) profile is linear with a positive slope when the spin label is attached to single stranded polynucleotides but exhibits discontinuities at certain critical temperatures when attached to the duplexes poly (As-U) and poly (I-Cs). These critical temperatures are lower than the optical Tm. Logarithmic increase in viscosity was found to produce a linear increase in tau in aqueous sucrose solutions."} {"id": "PMID:179061", "title": "[Animal experimental studies of positive tumor demonstration with radio-iodine labelled albumin macroaggregates].", "content": "131I-labeled macroaggregates were injected into the femoral artery of rats bearing a Yoshida sarcoma at the lower extremity and of healthy control animals. The radioactivity was measured in tissue samples taken from the tumour and in unaffected muscle tissue. The tumour tissue showed a considerably higher uptake of radioactivity than the not-neoplastic tissue of control animals. The difference was increased when more time elapsed between the injection and the measurement. After 48 hours the ratio was 25:1 in favour of tumour tissue. In contrast to the transplanted Yoshida sarcoma, hepatomas in Wistar rats induced by N-nitroso-morpholin showed a considerably smaller increase of radioactivity than the control group when injected with 131I-MAA. The fixation ratio between tumour and normal liver tissue was 1:5.9. In contrast to autochtone liver tumours rats with transplanted tumours are considered as a suitable model for testing labeled albumin particles like 131I-, 111In- or 99mTc-labelled albumin microspheres developed for angioscintigraphic purposes.", "contents": "[Animal experimental studies of positive tumor demonstration with radio-iodine labelled albumin macroaggregates]. 131I-labeled macroaggregates were injected into the femoral artery of rats bearing a Yoshida sarcoma at the lower extremity and of healthy control animals. The radioactivity was measured in tissue samples taken from the tumour and in unaffected muscle tissue. The tumour tissue showed a considerably higher uptake of radioactivity than the not-neoplastic tissue of control animals. The difference was increased when more time elapsed between the injection and the measurement. After 48 hours the ratio was 25:1 in favour of tumour tissue. In contrast to the transplanted Yoshida sarcoma, hepatomas in Wistar rats induced by N-nitroso-morpholin showed a considerably smaller increase of radioactivity than the control group when injected with 131I-MAA. The fixation ratio between tumour and normal liver tissue was 1:5.9. In contrast to autochtone liver tumours rats with transplanted tumours are considered as a suitable model for testing labeled albumin particles like 131I-, 111In- or 99mTc-labelled albumin microspheres developed for angioscintigraphic purposes."} {"id": "PMID:179065", "title": "A physiologic approach to cardiac rehabilitation.", "content": "Rehabilitation of the patient with atherosclerotic coronary heart disease is a longitudinal, comprehensive care program that ends only on the death of the patient. Although much remains to be learned about cardiac rehabilitation, there is a rational basis predicated upon causes of disability, healing of myocardial damage, energy cost of activities, a rational approach to the activity and exercise prescription, and the potential benefits from exercise to justify a concerted national rehabilitation effort. The potential benefits in terms of more rapid return to work, maintenance of the patient's psychosocial integrity, and modification of natural history of the disease make the institution of a cardiac rehabilitation program a prudent activity for a practitioner, clinic, or hospital.", "contents": "A physiologic approach to cardiac rehabilitation. Rehabilitation of the patient with atherosclerotic coronary heart disease is a longitudinal, comprehensive care program that ends only on the death of the patient. Although much remains to be learned about cardiac rehabilitation, there is a rational basis predicated upon causes of disability, healing of myocardial damage, energy cost of activities, a rational approach to the activity and exercise prescription, and the potential benefits from exercise to justify a concerted national rehabilitation effort. The potential benefits in terms of more rapid return to work, maintenance of the patient's psychosocial integrity, and modification of natural history of the disease make the institution of a cardiac rehabilitation program a prudent activity for a practitioner, clinic, or hospital."} {"id": "PMID:179066", "title": "Hypertension: medical and nursing implications.", "content": "Hypertension is a major public health problem affecting 20 to 30 million people in the United States, many of whom are undetected, untreated, or inadequately treated. Because hypertension often is asymptomatic for decades, it must be systematically sought out in apparently well persons if the condition is to be treated in its earliest stages and complications prevented. With the recent advent of effective antihypertensive medications treatment is available, once the patient has been diagnosed. Physicians and nurses have a major responsibility to direct the patient into treatment and to assure the effectiveness of his follow-up care. Noncompliance is a direct challenge to everyone seeing the patient. The patient must be motivated to accept and continue therapy through education and, most important, by the establishment of a good interpersonal relationship with the nurse and/or the physician.", "contents": "Hypertension: medical and nursing implications. Hypertension is a major public health problem affecting 20 to 30 million people in the United States, many of whom are undetected, untreated, or inadequately treated. Because hypertension often is asymptomatic for decades, it must be systematically sought out in apparently well persons if the condition is to be treated in its earliest stages and complications prevented. With the recent advent of effective antihypertensive medications treatment is available, once the patient has been diagnosed. Physicians and nurses have a major responsibility to direct the patient into treatment and to assure the effectiveness of his follow-up care. Noncompliance is a direct challenge to everyone seeing the patient. The patient must be motivated to accept and continue therapy through education and, most important, by the establishment of a good interpersonal relationship with the nurse and/or the physician."} {"id": "PMID:179067", "title": "Coronary artery surgery. Operative technique and patient education.", "content": "Coronary artery surgery, the preferred technique for myocardial revascularization in patients with ischemic heart disease, promptly increases blood flow to areas of the myocardium distal to the coronary obstruction. CAS completely relieves angina in 90% of patients. The risk of 1 to 5% is decreasing as operative technique and patient selection improve. Patients having CAS need comprehensive preoperative and discharge teaching to restore them to normal, active, optimistic lives.", "contents": "Coronary artery surgery. Operative technique and patient education. Coronary artery surgery, the preferred technique for myocardial revascularization in patients with ischemic heart disease, promptly increases blood flow to areas of the myocardium distal to the coronary obstruction. CAS completely relieves angina in 90% of patients. The risk of 1 to 5% is decreasing as operative technique and patient selection improve. Patients having CAS need comprehensive preoperative and discharge teaching to restore them to normal, active, optimistic lives."} {"id": "PMID:179076", "title": "[Cyclic AMP and asthma].", "content": "Recall is made of the essential notions concerning cyclic AMP, its biosynthesis, catabolism, mood of action, circumstances of its discovery. The relations with the alpha and beta adrenergic receptors allow to consider the part played by cyclic AMP in the physiopathology of the bronchial spasm.", "contents": "[Cyclic AMP and asthma]. Recall is made of the essential notions concerning cyclic AMP, its biosynthesis, catabolism, mood of action, circumstances of its discovery. The relations with the alpha and beta adrenergic receptors allow to consider the part played by cyclic AMP in the physiopathology of the bronchial spasm."} {"id": "PMID:179082", "title": "[State of the central regulation of glucocorticoid function of the adrenals in brain tumors].", "content": "Clinico-biochemical study of patients with tumours of the great hemispheres (75 observations) showed differences in the direction of reaction of the adrenal cortex to some actions. There was found a normal metopyron test, an inadequate activation in intensive stress action (an operation of removal of brain tumour) and a marked prolonged reaction to low stress stimulus (administration of low adrenaline doses). Several tests characterizing the function of negative reverse association mechanism and also reactions to stress actions of various intensity are necessary to assess the state of the central regulation of the glucocorticoid activity.", "contents": "[State of the central regulation of glucocorticoid function of the adrenals in brain tumors]. Clinico-biochemical study of patients with tumours of the great hemispheres (75 observations) showed differences in the direction of reaction of the adrenal cortex to some actions. There was found a normal metopyron test, an inadequate activation in intensive stress action (an operation of removal of brain tumour) and a marked prolonged reaction to low stress stimulus (administration of low adrenaline doses). Several tests characterizing the function of negative reverse association mechanism and also reactions to stress actions of various intensity are necessary to assess the state of the central regulation of the glucocorticoid activity."} {"id": "PMID:179083", "title": "[Aminoacyl-tRNA formation in the liver and skeletal muscles of rabbits under the influence of multiple injections of ACTH alone and in combination with sodium ribonucleinate].", "content": "A study was made of the action mechanism of ACTH. ACTH (10 Units/kg) alone or in combination with sodium ribonucleinate (10 mg/kg) was injected to rabbits for 14 days, daily. Sum total tRNA and aminoacyl-tRNA-synthetases were extracted from the liver and the skeletal muscles. tRNA acetylation with lysine-1-C14, leucine-1-C14 and alanine-1-C14 was investigated in vitro in homologous systems. It was found that repeated ACTH injections led to a decrease in the intensity of aminoacyl-tRNA formation in the liver and the skeletal muscles. When ACTH was injected in combination with sodium ribonucleinate formation of aminoacyl-tRNA was much more intensive in both organs than when ACTH was injected alone.", "contents": "[Aminoacyl-tRNA formation in the liver and skeletal muscles of rabbits under the influence of multiple injections of ACTH alone and in combination with sodium ribonucleinate]. A study was made of the action mechanism of ACTH. ACTH (10 Units/kg) alone or in combination with sodium ribonucleinate (10 mg/kg) was injected to rabbits for 14 days, daily. Sum total tRNA and aminoacyl-tRNA-synthetases were extracted from the liver and the skeletal muscles. tRNA acetylation with lysine-1-C14, leucine-1-C14 and alanine-1-C14 was investigated in vitro in homologous systems. It was found that repeated ACTH injections led to a decrease in the intensity of aminoacyl-tRNA formation in the liver and the skeletal muscles. When ACTH was injected in combination with sodium ribonucleinate formation of aminoacyl-tRNA was much more intensive in both organs than when ACTH was injected alone."} {"id": "PMID:179080", "title": "[Binding of H3-aldosterone to cytoplasmic receptors of the kidney in various functional states of the organ target].", "content": "A study was made of the capacity of the cytoplasmic cell fraction of rat kidney to bind H3-aldosterone, depending on the level of Na uptake with food, and, consequently, on the intensity of aldosterone secretion by the adrenal glands. It was shown by Sketchard's method that there existed in the cytoplasmic fraction of the kidney cells of rats with a high and low level of aldosterone secretion two classes of receptors binding aldosterone with a different degree of affinity. The number of binding sites for aldosterone in the 1st class of receptors, more specific for mineralocorticoids in the animals with a low level of aldosterone secretion (Na loading), was double that in comparison with the animals with a high level of aldosterone (Na deficiency). It is supposed that an increased aldosterone concentration in the organism in Na deficiency increased the transport of the specific hormone-receptor complex from the cytoplasm into the nucleus.", "contents": "[Binding of H3-aldosterone to cytoplasmic receptors of the kidney in various functional states of the organ target]. A study was made of the capacity of the cytoplasmic cell fraction of rat kidney to bind H3-aldosterone, depending on the level of Na uptake with food, and, consequently, on the intensity of aldosterone secretion by the adrenal glands. It was shown by Sketchard's method that there existed in the cytoplasmic fraction of the kidney cells of rats with a high and low level of aldosterone secretion two classes of receptors binding aldosterone with a different degree of affinity. The number of binding sites for aldosterone in the 1st class of receptors, more specific for mineralocorticoids in the animals with a low level of aldosterone secretion (Na loading), was double that in comparison with the animals with a high level of aldosterone (Na deficiency). It is supposed that an increased aldosterone concentration in the organism in Na deficiency increased the transport of the specific hormone-receptor complex from the cytoplasm into the nucleus."} {"id": "PMID:179084", "title": "[Specificity of the tibia test].", "content": "Studies on hypophysectomized immature female rats showed that the so-called tibia-test was highly specific only in testing the relatively pure preparations of growth hormone. Use of this test for determination of the content of growth hormone in the hypophysis or in the medium after the hypophysis incubation could lead to serious mistakes, since the majority of hypophysis hormones and many of the hormones of the peripheral endocrine glands were capable of influencing the width of the tibial cartilage in the hypophysectomized animals.", "contents": "[Specificity of the tibia test]. Studies on hypophysectomized immature female rats showed that the so-called tibia-test was highly specific only in testing the relatively pure preparations of growth hormone. Use of this test for determination of the content of growth hormone in the hypophysis or in the medium after the hypophysis incubation could lead to serious mistakes, since the majority of hypophysis hormones and many of the hormones of the peripheral endocrine glands were capable of influencing the width of the tibial cartilage in the hypophysectomized animals."} {"id": "PMID:179085", "title": "The solid phase synthesis of a protein activator for lecithin-cholesterol acyltransferase corresponding to human plasma apoC-I.", "content": "Apolipoprotein C-I, a protein constituent of the very low density lipoproteins of human plasma, consists of a single chain of 57 amino acids. The total synthesis of a protein corresponding to apolipoprotein C-I in physical properties and compositions was accomplished by solid phase techniques employing a modified polystrene incorporating spacer groups between the point of attachment of the first residue and the polymer matrix. The synthetic apoprotein was shown to activate lecithin:cholesterol acyltransferase to the same extent as the native protein. Comparative lipid-binding studies with dimyristoyl phosphatidylcholine gave complexes for native and synthetic apoprotein which floated at the same density after ultracentrifugation in KBr gradients and had virtually the same lipid:protein ratios.", "contents": "The solid phase synthesis of a protein activator for lecithin-cholesterol acyltransferase corresponding to human plasma apoC-I. Apolipoprotein C-I, a protein constituent of the very low density lipoproteins of human plasma, consists of a single chain of 57 amino acids. The total synthesis of a protein corresponding to apolipoprotein C-I in physical properties and compositions was accomplished by solid phase techniques employing a modified polystrene incorporating spacer groups between the point of attachment of the first residue and the polymer matrix. The synthetic apoprotein was shown to activate lecithin:cholesterol acyltransferase to the same extent as the native protein. Comparative lipid-binding studies with dimyristoyl phosphatidylcholine gave complexes for native and synthetic apoprotein which floated at the same density after ultracentrifugation in KBr gradients and had virtually the same lipid:protein ratios."} {"id": "PMID:179086", "title": "Binding of insulin to isolated nuclei.", "content": "Specific binding sites for 125I-labeled insulin were detected in purified nuclei isolated from rat liver. Binding was rapid, reversible and directly proportional to the number of nuclei employed. Unlabeled native insulin, at concentrations as low as 1ng/ml, significantly inhibited the binding of labeled hormone, whereas unlabeled proinsulin and desoctapeptide insulin were less potent. In contrast, glucagon, thyrotropin, growth hormone (somatotropin), and prolactin were without effect. Under identical incubation conditions, 125I-labeled glucagon bound to liver plasma membranes 5- to 10-fold more strongly than did insulin; in contrast glucoagon did not bind to liver nuclei. These studies demonstrate the presence of specific binding sites for insulin in purified nuclei isolated from rat liver. In addition, they suggest that the nucleus may be an intracellular site of insulin action.", "contents": "Binding of insulin to isolated nuclei. Specific binding sites for 125I-labeled insulin were detected in purified nuclei isolated from rat liver. Binding was rapid, reversible and directly proportional to the number of nuclei employed. Unlabeled native insulin, at concentrations as low as 1ng/ml, significantly inhibited the binding of labeled hormone, whereas unlabeled proinsulin and desoctapeptide insulin were less potent. In contrast, glucagon, thyrotropin, growth hormone (somatotropin), and prolactin were without effect. Under identical incubation conditions, 125I-labeled glucagon bound to liver plasma membranes 5- to 10-fold more strongly than did insulin; in contrast glucoagon did not bind to liver nuclei. These studies demonstrate the presence of specific binding sites for insulin in purified nuclei isolated from rat liver. In addition, they suggest that the nucleus may be an intracellular site of insulin action."} {"id": "PMID:179087", "title": "Mapping of the three species of polyoma mRNA.", "content": "The polyoma mRNA's present in the cytoplasm of primary cultures of mouse kidney cells during lytic infection were characterized by sedimentation velocity analysis and by hybridization to polyoma DNA fragments generated by a specific endonuclease of Hemophilus parainfluenzae (Hpa II).", "contents": "Mapping of the three species of polyoma mRNA. The polyoma mRNA's present in the cytoplasm of primary cultures of mouse kidney cells during lytic infection were characterized by sedimentation velocity analysis and by hybridization to polyoma DNA fragments generated by a specific endonuclease of Hemophilus parainfluenzae (Hpa II)."} {"id": "PMID:179088", "title": "Sequential transcription of the genes of vesicular stomatitis virus.", "content": "Increasing exposure of vesicular stomatitis virus particles to ultraviolet radiation caused differential inhibition of the synthesis in vitro of individual mRNA species which code for the viral structural proteins L, G, M, NS, and N.", "contents": "Sequential transcription of the genes of vesicular stomatitis virus. Increasing exposure of vesicular stomatitis virus particles to ultraviolet radiation caused differential inhibition of the synthesis in vitro of individual mRNA species which code for the viral structural proteins L, G, M, NS, and N."} {"id": "PMID:179089", "title": "Isolation and propagation of a segment of the simian virus 40 genome containing the origin of DNA replication.", "content": "Heteroduplex DNA molecules formed from two DNAs that differ from each other by a deletion can be cleaved at the mismatched region (a deletion loop) with the single-strand-specific S1 endonuclease. A heteroduplex DNA molecule, constructed from the DNA of simian virus 40 (SV40) mutant with a deletion of the map region 0.54-0.55 and the DNA of a second SV40 mutant having a deletion of the map segment 0.70-0.73, is cleaved twice with S1 endonuclease. One of the products is a DNA fragment of about 0.13 the length of SV40 DNA which contains the origin of SV40 DNA replication (0.67 on the SV40 DNA map).", "contents": "Isolation and propagation of a segment of the simian virus 40 genome containing the origin of DNA replication. Heteroduplex DNA molecules formed from two DNAs that differ from each other by a deletion can be cleaved at the mismatched region (a deletion loop) with the single-strand-specific S1 endonuclease. A heteroduplex DNA molecule, constructed from the DNA of simian virus 40 (SV40) mutant with a deletion of the map region 0.54-0.55 and the DNA of a second SV40 mutant having a deletion of the map segment 0.70-0.73, is cleaved twice with S1 endonuclease. One of the products is a DNA fragment of about 0.13 the length of SV40 DNA which contains the origin of SV40 DNA replication (0.67 on the SV40 DNA map)."} {"id": "PMID:179090", "title": "High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine.", "content": "Unlike normal cells, malignant rat and two simian virus 40-transformed human cell lines can neither grow nor survive in B12-and folate-supplemented media in which methionine is replaced by homocysteine. Yet three lines of evidence indicate that the malignant and transformed cells synthesize large amounts of methionine endogenously through the reaction catalyzed by 5-methyltetrahydropteroyl-L-glutamate; L-homocysteine S-methyltransferase (EC 2.1.1.13). (1) The activities of this methyltransferase were comparable in extracts of malignant and normal cells. (2) The uptake of radioactive label from [5-14C]methyltetrahydropteroyl-L-glutamic acid (5-Me-H4PteGlu) was at least as great in the malignant cells as in the normals and was nearly totally dependent on the addition of homocysteine, the methyl acceptor; furthermore, 59-84% of the label incorporated by cells was recovered as methionine.", "contents": "High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Unlike normal cells, malignant rat and two simian virus 40-transformed human cell lines can neither grow nor survive in B12-and folate-supplemented media in which methionine is replaced by homocysteine. Yet three lines of evidence indicate that the malignant and transformed cells synthesize large amounts of methionine endogenously through the reaction catalyzed by 5-methyltetrahydropteroyl-L-glutamate; L-homocysteine S-methyltransferase (EC 2.1.1.13). (1) The activities of this methyltransferase were comparable in extracts of malignant and normal cells. (2) The uptake of radioactive label from [5-14C]methyltetrahydropteroyl-L-glutamic acid (5-Me-H4PteGlu) was at least as great in the malignant cells as in the normals and was nearly totally dependent on the addition of homocysteine, the methyl acceptor; furthermore, 59-84% of the label incorporated by cells was recovered as methionine."} {"id": "PMID:179091", "title": "Hormone and neurotransmitter receptors in an established vascular endothelial cell line.", "content": "A cell line from the intima of the rabbit aorta has been established. This cell line exhibits strict contact inhibition, and morphologically resembles intimal endothelial cells. B-type blood group antigens and the presence of fibrinolytic activity also distinguish these cells from smooth muscle cells and from fibroblasts of the aortic wall. Endothelial cells were assayed for changes in levels of adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) in response to a series of vasoactive drugs. Control levels for cAMP and cGMP are 7.01 +/- 0.82 and 1.50 +/- 0.06, respectively (mean +/- SEM). Norepinephrine, acetylcholine, 5-hydroxytryptamine, and phenylephrine increased the levels of both nucleotides significantly. Propranolol (10-5 M) and phentolamine (10-5M) inhibited, respectively, the cAMP and cGMP response to norepinephrine. Angiotensin II and histamine significantly increased cGMP levels but not cAMP levels of the endothelial cells. The cGMP increases with acetylcholine were inhibited by atropine. These results indicate that the established cell line is endothelial in nature and contains cellular receptors to a variety of vasoactive agents.", "contents": "Hormone and neurotransmitter receptors in an established vascular endothelial cell line. A cell line from the intima of the rabbit aorta has been established. This cell line exhibits strict contact inhibition, and morphologically resembles intimal endothelial cells. B-type blood group antigens and the presence of fibrinolytic activity also distinguish these cells from smooth muscle cells and from fibroblasts of the aortic wall. Endothelial cells were assayed for changes in levels of adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) in response to a series of vasoactive drugs. Control levels for cAMP and cGMP are 7.01 +/- 0.82 and 1.50 +/- 0.06, respectively (mean +/- SEM). Norepinephrine, acetylcholine, 5-hydroxytryptamine, and phenylephrine increased the levels of both nucleotides significantly. Propranolol (10-5 M) and phentolamine (10-5M) inhibited, respectively, the cAMP and cGMP response to norepinephrine. Angiotensin II and histamine significantly increased cGMP levels but not cAMP levels of the endothelial cells. The cGMP increases with acetylcholine were inhibited by atropine. These results indicate that the established cell line is endothelial in nature and contains cellular receptors to a variety of vasoactive agents."} {"id": "PMID:179092", "title": "Sodium-stimulated amino acid uptake into isolated membrane vesicles from Balb/c 3T3 cells transformed by simian virus 40.", "content": "Mediated uptake of amino acids by membrane vesicles isolated from Balb/c 3T3 cells transformed by simian virus 40 has been demonstrated. Initial rates of transport of radioactively labeled L-leucine and alpha-aminoisobutyric acid were enhanced by the addition of NaCl (100 mM) to the reaction mixture at the start of the uptake process. This enhancement included a prominent \"overshoot\" during initial uptake. Slight stimulation of alpha-aminoisobutyric acid uptake was seen with K+, but none with Li+. The mediated nature of the uptake event for L-leucine was shown by saturation kinetics and by inhibition with L-valine. The transport assay measured predominantly intravesicular amino acid uptake rather than binding, as shown by the variation of uptake in response to changes in extravesicular osmolarity. Electron microscopy confirmed the presence of closed vesicles. Thus, amino acid transport has been characterized in an in vitro membrane vesicles system which should prove useful for studies of growth control.", "contents": "Sodium-stimulated amino acid uptake into isolated membrane vesicles from Balb/c 3T3 cells transformed by simian virus 40. Mediated uptake of amino acids by membrane vesicles isolated from Balb/c 3T3 cells transformed by simian virus 40 has been demonstrated. Initial rates of transport of radioactively labeled L-leucine and alpha-aminoisobutyric acid were enhanced by the addition of NaCl (100 mM) to the reaction mixture at the start of the uptake process. This enhancement included a prominent \"overshoot\" during initial uptake. Slight stimulation of alpha-aminoisobutyric acid uptake was seen with K+, but none with Li+. The mediated nature of the uptake event for L-leucine was shown by saturation kinetics and by inhibition with L-valine. The transport assay measured predominantly intravesicular amino acid uptake rather than binding, as shown by the variation of uptake in response to changes in extravesicular osmolarity. Electron microscopy confirmed the presence of closed vesicles. Thus, amino acid transport has been characterized in an in vitro membrane vesicles system which should prove useful for studies of growth control."} {"id": "PMID:179093", "title": "Resting state in normal and simian virus 40 transformed Chinese hamster lung cells.", "content": "Normal cell deprived of amino acids or serum factors enter a resting state, whereas cells transformed by wild-type simian virus 40 do not. The ability to enter a resting state is temperature-sensitive (ts) in cells transformed by a tsA mutant of simian virus 40. We shown further: (i) that when complete medium is added to resting cells, the length of time until the onset of DNA synthesis often exceeds the length of G1 in growing cells; (ii) that the length of this interval depends upon the conditions used to arrest cell growth; but (iii) that transferring cultures from medium depleted for one factor to medium depleted in a second factor never leads to a round of DNA synthesis; and (iv) that DNA synthesis does not resume rapidly when a resting culture of cells transformed by the tsA mutant is transferred to the permissive temperature in suboptimal medium. A model proposing that in suboptimal conditions cells leave the cell cycle and traverse a branch pathway to enter the resting state is consistent with these findings.", "contents": "Resting state in normal and simian virus 40 transformed Chinese hamster lung cells. Normal cell deprived of amino acids or serum factors enter a resting state, whereas cells transformed by wild-type simian virus 40 do not. The ability to enter a resting state is temperature-sensitive (ts) in cells transformed by a tsA mutant of simian virus 40. We shown further: (i) that when complete medium is added to resting cells, the length of time until the onset of DNA synthesis often exceeds the length of G1 in growing cells; (ii) that the length of this interval depends upon the conditions used to arrest cell growth; but (iii) that transferring cultures from medium depleted for one factor to medium depleted in a second factor never leads to a round of DNA synthesis; and (iv) that DNA synthesis does not resume rapidly when a resting culture of cells transformed by the tsA mutant is transferred to the permissive temperature in suboptimal medium. A model proposing that in suboptimal conditions cells leave the cell cycle and traverse a branch pathway to enter the resting state is consistent with these findings."} {"id": "PMID:179094", "title": "Hormonal control of meiosis: specificity of the 1-methyladenine receptors in starfish oocytes.", "content": "The specificity of the 1-methyladenine receptors, which are localized on the cell membrane of starfish oocytes, has been investigated in Marthasterias glacialis and Asterias rubens. Ability of N-1-substituted adenines to trigger the release of meiosis inhibition is conserved, or even increased, when the methyl group is replaced by larger substituent groups.", "contents": "Hormonal control of meiosis: specificity of the 1-methyladenine receptors in starfish oocytes. The specificity of the 1-methyladenine receptors, which are localized on the cell membrane of starfish oocytes, has been investigated in Marthasterias glacialis and Asterias rubens. Ability of N-1-substituted adenines to trigger the release of meiosis inhibition is conserved, or even increased, when the methyl group is replaced by larger substituent groups."} {"id": "PMID:179095", "title": "Cholera toxin interactions with thyrotropin receptors on thyroid plasma membranes.", "content": "Unlabeled cholera toxin inhibits [125I]thyrotropin binding to thyrotropin receptors on thyroid plasma membranes. Maximal inhibition by cholera toxin does not exceed 40%, whereas unalbeled thyrotropin completely inhibits [125I]thyrotropin binding to these same membranes. Kinetic analyses of the binding data are compatible with the view that the cholera toxin decreases the number of receptor sites available to thyrotropin and that the mechanism by which the cholera toxin inhibits [125I]thyrotropin binding to these receptor sites involves both competitive and noncompetitive elements.", "contents": "Cholera toxin interactions with thyrotropin receptors on thyroid plasma membranes. Unlabeled cholera toxin inhibits [125I]thyrotropin binding to thyrotropin receptors on thyroid plasma membranes. Maximal inhibition by cholera toxin does not exceed 40%, whereas unalbeled thyrotropin completely inhibits [125I]thyrotropin binding to these same membranes. Kinetic analyses of the binding data are compatible with the view that the cholera toxin decreases the number of receptor sites available to thyrotropin and that the mechanism by which the cholera toxin inhibits [125I]thyrotropin binding to these receptor sites involves both competitive and noncompetitive elements."} {"id": "PMID:179096", "title": "Effects of concanavalin A and a succinylated derivative on lymphocyte proliferation and cyclic nucleotide levels.", "content": "To better define cell surface-related changes involved in lymphocyte activation, we studied native concanavalin A (Con A) and succinylated concanavalin A (Suc-Con A) for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the two forms of Con A induce equivalent proliferation; however, the mitogenic activity of Con A progressively decreases above 50 mug/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 mug/ml.", "contents": "Effects of concanavalin A and a succinylated derivative on lymphocyte proliferation and cyclic nucleotide levels. To better define cell surface-related changes involved in lymphocyte activation, we studied native concanavalin A (Con A) and succinylated concanavalin A (Suc-Con A) for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the two forms of Con A induce equivalent proliferation; however, the mitogenic activity of Con A progressively decreases above 50 mug/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 mug/ml."} {"id": "PMID:179097", "title": "Search for antigens and antibodies crossreactive with type C viruses of the woolly monkeys and gibbon ape in animal models and in humans.", "content": "Several reports have indicated the presence of type-C viral antigens in human tumors and of viruses closely related to those of the woolly monkey and gibbon ape in cultured human cells. In the present studies, attempts to detect woolly monkeys viral antigens in human tissues, or antibodies directed against structural polypeptides of woolly monkey viruses in human sera, were unsuccessful, In contrast, it was possible to demonstrate viral antigens in tissues and antibodies reactive to viral components in several animal and even primate model systems. Further evidence against the presence of woolly monkey viruses in humans is our failure to identify spontaneous or chemically induced viruses of this group in more than 200 individual cultures of human origin examined. These findings argue against the likelihood that viruses closely related to the woolly monkeys virus are associated with human tumors or are common infectious agents of man.", "contents": "Search for antigens and antibodies crossreactive with type C viruses of the woolly monkeys and gibbon ape in animal models and in humans. Several reports have indicated the presence of type-C viral antigens in human tumors and of viruses closely related to those of the woolly monkey and gibbon ape in cultured human cells. In the present studies, attempts to detect woolly monkeys viral antigens in human tissues, or antibodies directed against structural polypeptides of woolly monkey viruses in human sera, were unsuccessful, In contrast, it was possible to demonstrate viral antigens in tissues and antibodies reactive to viral components in several animal and even primate model systems. Further evidence against the presence of woolly monkey viruses in humans is our failure to identify spontaneous or chemically induced viruses of this group in more than 200 individual cultures of human origin examined. These findings argue against the likelihood that viruses closely related to the woolly monkeys virus are associated with human tumors or are common infectious agents of man."} {"id": "PMID:179098", "title": "Differential effect of phosphonoacetic acid on the expression of Epstein-Barr viral antigens and virus production.", "content": "The effects of phosphonoacetic acid on cell growth, expression of Epstein-Barr virus antigens, and virus production in human and marmoset lymphoblastoid cell lines have been studied. The drug had no significant effect at concentrations up to 100 mug/ml on cell growth or total cell DNA synthesis. Higher doses induced not only a drastic decrease in DNA synthesis and cell grwoth, but also a dramatic cell enlargement. Immunofluorescence studies showed that greater than or equal to 30 mug/ml of phosphonoacetic acid inhibited viral capsid antigen synthesis without affecting the expression of the nuclear antigen or the spontaneous and 5-iodo-2'-deoxyuridine-induced early antigens. Production of transforming Epstein-Barr virus was also blocked.", "contents": "Differential effect of phosphonoacetic acid on the expression of Epstein-Barr viral antigens and virus production. The effects of phosphonoacetic acid on cell growth, expression of Epstein-Barr virus antigens, and virus production in human and marmoset lymphoblastoid cell lines have been studied. The drug had no significant effect at concentrations up to 100 mug/ml on cell growth or total cell DNA synthesis. Higher doses induced not only a drastic decrease in DNA synthesis and cell grwoth, but also a dramatic cell enlargement. Immunofluorescence studies showed that greater than or equal to 30 mug/ml of phosphonoacetic acid inhibited viral capsid antigen synthesis without affecting the expression of the nuclear antigen or the spontaneous and 5-iodo-2'-deoxyuridine-induced early antigens. Production of transforming Epstein-Barr virus was also blocked."} {"id": "PMID:179099", "title": "Evidence for tandem integration of avian myeloblastosis virus DNA with endogenous provirus in leukemic chicken cells.", "content": "The integration site of avian myeloblastosis virus (AMV) proviral DNA in DNA from leukemia chicken myeloblasts has been studied by three sequential nucleic acid hybridizations that can localize the proviral DNA according to the repetitiveness of the adjacent cellular DNA regions. First, large denatured cellular DNA fragments (2.1 x 10(6) daltons) were reassociated and fractionated according to sequence reiteration frequenct. Next, DNA remaining single-stranded in each fraction was immobilized on nitrocellulose filters hybridized with an excess of unlabeled 70S RNA from Rous-associated virus-0 to saturate the endogenous proviral DNA sequences.", "contents": "Evidence for tandem integration of avian myeloblastosis virus DNA with endogenous provirus in leukemic chicken cells. The integration site of avian myeloblastosis virus (AMV) proviral DNA in DNA from leukemia chicken myeloblasts has been studied by three sequential nucleic acid hybridizations that can localize the proviral DNA according to the repetitiveness of the adjacent cellular DNA regions. First, large denatured cellular DNA fragments (2.1 x 10(6) daltons) were reassociated and fractionated according to sequence reiteration frequenct. Next, DNA remaining single-stranded in each fraction was immobilized on nitrocellulose filters hybridized with an excess of unlabeled 70S RNA from Rous-associated virus-0 to saturate the endogenous proviral DNA sequences."} {"id": "PMID:179103", "title": "Lipid mobilizing hormones of the hypothalamus and pituitary.", "content": "Lipid mobilizing substances (LMS) are present in the hypothalamus and pituitary of mammals and probably are involved in the central neural control of obesity. Most of these have direct lipolytic effects, like lipid mobilizing factor (LMF) and LH-RH from the hypothalamus as well as lipotropin (LPH), melanocyte-stimulating hormone (MSH), corticotropin (ACTH), and growth hormone (GH) from the pituitary gland. Some of the substances, like GH-release inhibiting hormone (GH-RIH), affect lipolysis by secondary actions on pancreatic hormones such as insulin and glucagon. Other hypothalamic hormones, like GH-releasing hormone (GH-RH) may influence lipolysis secondarily through the pituitary hormones (e.g. GH) whose release they control. Regardless of how lipid mobilization is affected, investigations into the problem of obesity should take these LMS into consideration.", "contents": "Lipid mobilizing hormones of the hypothalamus and pituitary. Lipid mobilizing substances (LMS) are present in the hypothalamus and pituitary of mammals and probably are involved in the central neural control of obesity. Most of these have direct lipolytic effects, like lipid mobilizing factor (LMF) and LH-RH from the hypothalamus as well as lipotropin (LPH), melanocyte-stimulating hormone (MSH), corticotropin (ACTH), and growth hormone (GH) from the pituitary gland. Some of the substances, like GH-release inhibiting hormone (GH-RIH), affect lipolysis by secondary actions on pancreatic hormones such as insulin and glucagon. Other hypothalamic hormones, like GH-releasing hormone (GH-RH) may influence lipolysis secondarily through the pituitary hormones (e.g. GH) whose release they control. Regardless of how lipid mobilization is affected, investigations into the problem of obesity should take these LMS into consideration."} {"id": "PMID:179104", "title": "Mechanism of actions of adrenaline and ACTH in fat mobilization.", "content": "Starvation did not cause increase of hormone-sensitive lipase in rat epididymal adipose tissue. Adrenaline did not activate lipase in the fat cells, although it accelerated the release of free fatty acids from the cells. The results suggest that the mechanism of the stimulation of lipolysis by adrenaline is different from that in the cyclic AMP theory. Adrenaline-sensitive fat globules were prepared by hypotonic treatment of fat cells. Lipolysis in the fat globules was stimulated by adrenaline. It was shown that adrenaline-induced lipolysis in the fat globules was not due to activation of lipase but to initiation of a reaction between lipase and triglyceride. It is well known that calcium ions are essential for ACTH-induced lipolysis and that the hormone stimulates calcium uptake into adipose tissue. It was demonstrated that calcium ions accelerated formation of a complex between fat and lipase. The mechanism of the actions of adrenaline and ACTH are discussed on the basis of these results.", "contents": "Mechanism of actions of adrenaline and ACTH in fat mobilization. Starvation did not cause increase of hormone-sensitive lipase in rat epididymal adipose tissue. Adrenaline did not activate lipase in the fat cells, although it accelerated the release of free fatty acids from the cells. The results suggest that the mechanism of the stimulation of lipolysis by adrenaline is different from that in the cyclic AMP theory. Adrenaline-sensitive fat globules were prepared by hypotonic treatment of fat cells. Lipolysis in the fat globules was stimulated by adrenaline. It was shown that adrenaline-induced lipolysis in the fat globules was not due to activation of lipase but to initiation of a reaction between lipase and triglyceride. It is well known that calcium ions are essential for ACTH-induced lipolysis and that the hormone stimulates calcium uptake into adipose tissue. It was demonstrated that calcium ions accelerated formation of a complex between fat and lipase. The mechanism of the actions of adrenaline and ACTH are discussed on the basis of these results."} {"id": "PMID:179105", "title": "Fiber connections in the hypothalamus and some autonomic functions.", "content": "The ventromedial hypothalamic nucleus (VMH) belongs to area sympathica B of the SPH-System and its fibers to make up the dorsal longitudinal fasciculus and the hypothalamicotegmental tract. Blood glucose increases by rapid increase in active phosphorylase and G-6-Pase activities in liver following VMH stimulation. From the changes of ultrastructure of the hypophysis and the pancreas, GH, ACTH, LH, FSH and TSH (but not prolactin) are thought to be released by each releasing hormone increased by VMH stimulation. D cell hormone is also released and insulin is not released following VMH stimulation. The lateral hypothalamic nucleus (LH) belongs to area parasympathica C of the SPH-System and its fibers to make up the medial forebrain bundle and stria medullaris. Blood glucose decreases by relatively rapid increase in glycogen synthetase activity in the liver following LH stimulation. From the changes of ultrastructure, GH, ACTH, LH, FSH, TSH and D cell hormone are not released, but prolaction and insulin are released following LH stimulation. By giving lesions in VMH or LH, some degenerated fibers could be seen in LH or VMH, homolaterally.", "contents": "Fiber connections in the hypothalamus and some autonomic functions. The ventromedial hypothalamic nucleus (VMH) belongs to area sympathica B of the SPH-System and its fibers to make up the dorsal longitudinal fasciculus and the hypothalamicotegmental tract. Blood glucose increases by rapid increase in active phosphorylase and G-6-Pase activities in liver following VMH stimulation. From the changes of ultrastructure of the hypophysis and the pancreas, GH, ACTH, LH, FSH and TSH (but not prolactin) are thought to be released by each releasing hormone increased by VMH stimulation. D cell hormone is also released and insulin is not released following VMH stimulation. The lateral hypothalamic nucleus (LH) belongs to area parasympathica C of the SPH-System and its fibers to make up the medial forebrain bundle and stria medullaris. Blood glucose decreases by relatively rapid increase in glycogen synthetase activity in the liver following LH stimulation. From the changes of ultrastructure, GH, ACTH, LH, FSH, TSH and D cell hormone are not released, but prolaction and insulin are released following LH stimulation. By giving lesions in VMH or LH, some degenerated fibers could be seen in LH or VMH, homolaterally."} {"id": "PMID:179109", "title": "Control of asthma in children.", "content": "Programs designed for the control of asthma are complex. Implementation of a number of modalities may be necessary, and the mean and level of treatment may need to be varied from time to time. Medical treatment is a primary concern but preventive measures and education of the family are essential as well.", "contents": "Control of asthma in children. Programs designed for the control of asthma are complex. Implementation of a number of modalities may be necessary, and the mean and level of treatment may need to be varied from time to time. Medical treatment is a primary concern but preventive measures and education of the family are essential as well."} {"id": "PMID:179111", "title": "[Differential diagnosis of neck tumors by angiography (author's transl)].", "content": "Angiographic criteria and differential dignosis of tumors of the lateral neck are demonstrated in 200 examined patients. There is a typical angiographic pattern in chemodectomas. Extreme vascularization and localization in the area of the carotid bifurcation are characteristic for these tumors. Neurinomas are avascular or minimally vascularized. The character of carotid artery deviation allows to distinguish neurinomas from other neoplasms of the neck. Metastases of thyroidal carcinoma are usually represented by pronounced vascularized tumors with a smooth border. Metastases of squamous cell carcinomas as primary mesenchymal tumors are minimally vascularized or sometimes avascular. There is increased vascularization in combination with perifocal inflammation. It is impossible to differentiate metastases of squamous cell carcinomas from primary mesenchymal tumors by angiography.", "contents": "[Differential diagnosis of neck tumors by angiography (author's transl)]. Angiographic criteria and differential dignosis of tumors of the lateral neck are demonstrated in 200 examined patients. There is a typical angiographic pattern in chemodectomas. Extreme vascularization and localization in the area of the carotid bifurcation are characteristic for these tumors. Neurinomas are avascular or minimally vascularized. The character of carotid artery deviation allows to distinguish neurinomas from other neoplasms of the neck. Metastases of thyroidal carcinoma are usually represented by pronounced vascularized tumors with a smooth border. Metastases of squamous cell carcinomas as primary mesenchymal tumors are minimally vascularized or sometimes avascular. There is increased vascularization in combination with perifocal inflammation. It is impossible to differentiate metastases of squamous cell carcinomas from primary mesenchymal tumors by angiography."} {"id": "PMID:179118", "title": "Effect of anti-mouse macrophage serum on murine cytomegalovirus infection.", "content": "Rabbit anti-mouse macrophage serum (AMS) was used to study the role played by macrophages against murine cytomegalovirus infection. Treatment of mice with AMS enhanced morbidity and mortality following virus infection. These results are discussed in relation to the role of macrophages against virus infections.", "contents": "Effect of anti-mouse macrophage serum on murine cytomegalovirus infection. Rabbit anti-mouse macrophage serum (AMS) was used to study the role played by macrophages against murine cytomegalovirus infection. Treatment of mice with AMS enhanced morbidity and mortality following virus infection. These results are discussed in relation to the role of macrophages against virus infections."} {"id": "PMID:179119", "title": "On the formation of hydrogen peroxide and oxygen radicals in heart mitochondria.", "content": "The mitochondrial respiratory chain has been shown to produce H2O2 under certain conditions (Loschen, Flohe, and Chance, 1971; Boveris, Oshino, and Chance, 1972; Loschen, Azzui, and Flohe, 1973; Boveris and Chance, 1973). At least 1 percent of the total oxygen uptake in State 4 (Chance and Williams, 1956) in the presence of succinate is caused by H2O2 formation (Boveris et al., 1972). It was shown that the component responsible for mitochondrial H2O2 formation is located between the sites of the antimycin and rotenone inhibition (Loschen et al., 1971; Boveris et al., 1972). The possible physiological consequences of a respiratory chain-linked H2O2 formation is not yet understood. It would therefore be of significance to know whether oxygen radicals are involved in this process or not. It was recently suggested by Rotilio et al. (1973) that enzyme systems producing H2O2 via oxygen radicals are always closely associated with a superoxide dismutase. Thus, the existence of a mitochondrial superoxide dismutase located in the matrix space (Weisiger and Fridovich, 1973) prompted us to look for oxygen radicals as possible intermediates in the mechanism of the formation of mitochondrial H2O2. In the present communication we show that, under the same conditions in which H2O2 is formed in the mitochondrial respiratoy chain, oxygen radical formation can be demonstrated also. A possible relationship of this finding with lipid peroxidation and the toxic effects of hyperbaric oxygen is likely.", "contents": "On the formation of hydrogen peroxide and oxygen radicals in heart mitochondria. The mitochondrial respiratory chain has been shown to produce H2O2 under certain conditions (Loschen, Flohe, and Chance, 1971; Boveris, Oshino, and Chance, 1972; Loschen, Azzui, and Flohe, 1973; Boveris and Chance, 1973). At least 1 percent of the total oxygen uptake in State 4 (Chance and Williams, 1956) in the presence of succinate is caused by H2O2 formation (Boveris et al., 1972). It was shown that the component responsible for mitochondrial H2O2 formation is located between the sites of the antimycin and rotenone inhibition (Loschen et al., 1971; Boveris et al., 1972). The possible physiological consequences of a respiratory chain-linked H2O2 formation is not yet understood. It would therefore be of significance to know whether oxygen radicals are involved in this process or not. It was recently suggested by Rotilio et al. (1973) that enzyme systems producing H2O2 via oxygen radicals are always closely associated with a superoxide dismutase. Thus, the existence of a mitochondrial superoxide dismutase located in the matrix space (Weisiger and Fridovich, 1973) prompted us to look for oxygen radicals as possible intermediates in the mechanism of the formation of mitochondrial H2O2. In the present communication we show that, under the same conditions in which H2O2 is formed in the mitochondrial respiratoy chain, oxygen radical formation can be demonstrated also. A possible relationship of this finding with lipid peroxidation and the toxic effects of hyperbaric oxygen is likely."} {"id": "PMID:179120", "title": "Adrenaline, noradrenaline, and adenosine 3',5'-monophosphate levels in plasma of healthy persons during ergometric work with and without beta-receptor blocking agents.", "content": "After endogeneous increase of noradrenaline and adrenaline during a submaximal exercise test, plasma levels of adenosine 3',5'-monophosphate (cyclic AMP) show no significant change. After effective beta-receptor blockade due to propranolol plasma levels of cyclie AMP do not change significantly, either during rest or during exericse. After effective beta-receptor blockade due to propranolol the plasma levels of noradrenaline and adrenaline, reached during exercise, are significantly reduced compared with the plasma catecholamine levels obtained under the same exercise conditions wtihout beta-blockade. In contrast to the findings of other investigators, increased plasma catecholamine levels after administration of propranolol could not be observed.", "contents": "Adrenaline, noradrenaline, and adenosine 3',5'-monophosphate levels in plasma of healthy persons during ergometric work with and without beta-receptor blocking agents. After endogeneous increase of noradrenaline and adrenaline during a submaximal exercise test, plasma levels of adenosine 3',5'-monophosphate (cyclic AMP) show no significant change. After effective beta-receptor blockade due to propranolol plasma levels of cyclie AMP do not change significantly, either during rest or during exericse. After effective beta-receptor blockade due to propranolol the plasma levels of noradrenaline and adrenaline, reached during exercise, are significantly reduced compared with the plasma catecholamine levels obtained under the same exercise conditions wtihout beta-blockade. In contrast to the findings of other investigators, increased plasma catecholamine levels after administration of propranolol could not be observed."} {"id": "PMID:179121", "title": "Catecholamine antagonism of acetylcholine and dibutyrl guanosine 3',-5'-monophosphate in the mammalian ventricular myocardium.", "content": "After chemical sympathectomy we could demonstrate a negative inotropic effect of acetylcholine (ACh) on the cat ventricular myocardium as a direct catecholamine antagonism. Dose-response relationships for isoproterenol (IP) reveal a noncompetitive inhibition of the inotropic action of the catecholamine by ACh. A concentration of 10(-6) M ACh reduced the maximal IP-induced increase in tension by 58 +/- 13 percent (6-hydroxydopamine pretreatment) and by 65 +/- 10 percent (reserpine pretreatment); inhibition by endogenous ACh (released by field stimulation) was 36 +/- 10 percent and 38 +/- 8 percent, respectively. A concentration of 10(-3) M bibutyryl guanosine 3',5'-monophosphate (cAMP) produced a 17 +/- 7 percent reduction of the catecholamine-induced increase in tension (reserpine pretreatment). A cholinergic influence on the myocardial mechanics and metabolism of the heart may be relevant under stress situations. Vagal inhibition of the ventricular function is accentuated by an elevated sympathetic tone (Levy, 1971). If catecholamine-induced myocardial necrosis in addition to secondary effects of altered vessels are produced also by direct damage of the myocardial cell, then an influence of acetylcholine as a \"natural\" antagonist may be important.", "contents": "Catecholamine antagonism of acetylcholine and dibutyrl guanosine 3',-5'-monophosphate in the mammalian ventricular myocardium. After chemical sympathectomy we could demonstrate a negative inotropic effect of acetylcholine (ACh) on the cat ventricular myocardium as a direct catecholamine antagonism. Dose-response relationships for isoproterenol (IP) reveal a noncompetitive inhibition of the inotropic action of the catecholamine by ACh. A concentration of 10(-6) M ACh reduced the maximal IP-induced increase in tension by 58 +/- 13 percent (6-hydroxydopamine pretreatment) and by 65 +/- 10 percent (reserpine pretreatment); inhibition by endogenous ACh (released by field stimulation) was 36 +/- 10 percent and 38 +/- 8 percent, respectively. A concentration of 10(-3) M bibutyryl guanosine 3',5'-monophosphate (cAMP) produced a 17 +/- 7 percent reduction of the catecholamine-induced increase in tension (reserpine pretreatment). A cholinergic influence on the myocardial mechanics and metabolism of the heart may be relevant under stress situations. Vagal inhibition of the ventricular function is accentuated by an elevated sympathetic tone (Levy, 1971). If catecholamine-induced myocardial necrosis in addition to secondary effects of altered vessels are produced also by direct damage of the myocardial cell, then an influence of acetylcholine as a \"natural\" antagonist may be important."} {"id": "PMID:179122", "title": "Recruitment and discharge frequency of phrenic motoneurones during inspiration.", "content": "The discharges of 107 phrenic motor axons were recorded from cats under chloralose-urethane anaesthesia with spinal cords transected at T1 or with intact neuraxis. During inspiratory occlusions in spinal cats, each motoneurone was recruited at a mouth pressure constant at a given end tidal CO2; no motoneurone was recruited at a pressure greater than 70% of maximum. In eupnoea (32.3 torr CO2) 73% of motoneurones were recruited during the first 30% of inspiration; during CO2 rebreathing (60.8 torr CO2), 89% were recruited in the first 30% of inspiration. Neurones recruited earlier in inspiration had a lower onset frequency than later recruited units; all increased instantaneous frequency in a linear relation to pressure. Early recruited units showed a smaller increase in frequency per unit change in pressure than did later recruited units. During CO2 rebreathing, mean and peak frequencies increased on average 0.92 and 1.78 spikes.sec(-1) (%CO2)(-1), respectively, these increases being significantly less for early than for late recruited neurones. The data show that a stable order of recruitment of phrenic motoneurones exists during inspiration, the excitability of each motoneurone likely determining its time of recruitment. Above threshold, later recruited motoneurones are more 'sensitive' to a change in input. Recruitment of motoneurones is responsible for pressure generation at the start of inspiration and increase in discharge frequency (rate coding) is the dominant mechanism in the second half of inspiration.", "contents": "Recruitment and discharge frequency of phrenic motoneurones during inspiration. The discharges of 107 phrenic motor axons were recorded from cats under chloralose-urethane anaesthesia with spinal cords transected at T1 or with intact neuraxis. During inspiratory occlusions in spinal cats, each motoneurone was recruited at a mouth pressure constant at a given end tidal CO2; no motoneurone was recruited at a pressure greater than 70% of maximum. In eupnoea (32.3 torr CO2) 73% of motoneurones were recruited during the first 30% of inspiration; during CO2 rebreathing (60.8 torr CO2), 89% were recruited in the first 30% of inspiration. Neurones recruited earlier in inspiration had a lower onset frequency than later recruited units; all increased instantaneous frequency in a linear relation to pressure. Early recruited units showed a smaller increase in frequency per unit change in pressure than did later recruited units. During CO2 rebreathing, mean and peak frequencies increased on average 0.92 and 1.78 spikes.sec(-1) (%CO2)(-1), respectively, these increases being significantly less for early than for late recruited neurones. The data show that a stable order of recruitment of phrenic motoneurones exists during inspiration, the excitability of each motoneurone likely determining its time of recruitment. Above threshold, later recruited motoneurones are more 'sensitive' to a change in input. Recruitment of motoneurones is responsible for pressure generation at the start of inspiration and increase in discharge frequency (rate coding) is the dominant mechanism in the second half of inspiration."} {"id": "PMID:179123", "title": "[The hemarthroses of articular chondrocalcinosis].", "content": "Spontaneous haemarthrosis may occur during the evolution of articular chondrocalcinosis. It occurs mainly in older women and involves the knee in particular. The disorder may recur in the same or in different joints. A study of 11 case histories and counts of red blood corpuscles in samples of synovial fluid confirm that bleeding occurs more readily in chondrocalcinosis than in arthrosis alone. The proposed mechanism of haemarthrosis is only a hypothesis, but it is possible to imagine the onset of microcrystalline flow in a joint that is senile and affected by arthrosis. It is suspected that repeated haemarthrosis favours an oseolytic evolution in certain cases of chondrocalcinosis.", "contents": "[The hemarthroses of articular chondrocalcinosis]. Spontaneous haemarthrosis may occur during the evolution of articular chondrocalcinosis. It occurs mainly in older women and involves the knee in particular. The disorder may recur in the same or in different joints. A study of 11 case histories and counts of red blood corpuscles in samples of synovial fluid confirm that bleeding occurs more readily in chondrocalcinosis than in arthrosis alone. The proposed mechanism of haemarthrosis is only a hypothesis, but it is possible to imagine the onset of microcrystalline flow in a joint that is senile and affected by arthrosis. It is suspected that repeated haemarthrosis favours an oseolytic evolution in certain cases of chondrocalcinosis."} {"id": "PMID:179126", "title": "Thyroxine, triiodothyronine, and thyrotropin in serum during long-term diphenylhydantoin therapy.", "content": "Clinical laboratory tests for assessment of thyroid function were performed in 31 patients receiving long-term diphenylhydantoin (DPH) therapy. Reduced serum total thyroxine and free thyroxine index were found. The decrease in serum total triiodothyronine and free triiodothyronine index was smaller but statistically significant. DPH had no significant effect on the serum thyrotropin (TSH) concentration and maximal TSH response to TSH-releasing hormone. The absence of reciprocal changes in TSH and serum thyroxine might be due to the near-normal triiodothyronine concentration. Such an explanation would also conform with previous findings that the pituitary contains specific receptors for triiodothyronine but not thyroxine.", "contents": "Thyroxine, triiodothyronine, and thyrotropin in serum during long-term diphenylhydantoin therapy. Clinical laboratory tests for assessment of thyroid function were performed in 31 patients receiving long-term diphenylhydantoin (DPH) therapy. Reduced serum total thyroxine and free thyroxine index were found. The decrease in serum total triiodothyronine and free triiodothyronine index was smaller but statistically significant. DPH had no significant effect on the serum thyrotropin (TSH) concentration and maximal TSH response to TSH-releasing hormone. The absence of reciprocal changes in TSH and serum thyroxine might be due to the near-normal triiodothyronine concentration. Such an explanation would also conform with previous findings that the pituitary contains specific receptors for triiodothyronine but not thyroxine."} {"id": "PMID:179127", "title": "Determination of cyclic adenosine 3',5'-monophosphate in urine.", "content": "A modification of Aurbach & Houston's enzymic method for measuring cAMP is presented. The procedure is relatively simple and in several respects new. Urinary cAMP is separated from other nucleotides and phosphate by ZnSO4-Ba(OH)2 precipitation and column chromatography. The eluate is concentrated by evaporation. Recovery at this stage is 60-82%. The cAMP from urine and the standards are dissolved in a reaction mixture and converted to 5-AMP with cyclic 3',5'-nucleotide phosphodiesterase (PDE) and further to ATP with adenylate kinase and pyruvate kinase. The ATP formed is labelled with 32P by an exchange reaction catalysed by glyceraldehyde phosphate dehydrogenase and phosphoglycerate kinase. The remaining 32P used to count the [32P]ATP in the aqueous phase. Daily human urinary cAMP excretion is 3380 +/- 836 nmol (S.D.). After an injection of 100 USP units of parathormone intravenously into a patient with idiopathic hypoparathyroidism, urinary cAMP excretion increased 40-fold above the basal concentration within 30 min. Drinking of coffee or water did not affect cAMP excretion. The limit of detection of the method is 170 pmol of cAMP, and the variation coefficient for urine ranges from 7 to 10%. When the enzymic cAMP method was compared with a radioimmunological procedure, the correlation coefficient was found to be 0.98.", "contents": "Determination of cyclic adenosine 3',5'-monophosphate in urine. A modification of Aurbach & Houston's enzymic method for measuring cAMP is presented. The procedure is relatively simple and in several respects new. Urinary cAMP is separated from other nucleotides and phosphate by ZnSO4-Ba(OH)2 precipitation and column chromatography. The eluate is concentrated by evaporation. Recovery at this stage is 60-82%. The cAMP from urine and the standards are dissolved in a reaction mixture and converted to 5-AMP with cyclic 3',5'-nucleotide phosphodiesterase (PDE) and further to ATP with adenylate kinase and pyruvate kinase. The ATP formed is labelled with 32P by an exchange reaction catalysed by glyceraldehyde phosphate dehydrogenase and phosphoglycerate kinase. The remaining 32P used to count the [32P]ATP in the aqueous phase. Daily human urinary cAMP excretion is 3380 +/- 836 nmol (S.D.). After an injection of 100 USP units of parathormone intravenously into a patient with idiopathic hypoparathyroidism, urinary cAMP excretion increased 40-fold above the basal concentration within 30 min. Drinking of coffee or water did not affect cAMP excretion. The limit of detection of the method is 170 pmol of cAMP, and the variation coefficient for urine ranges from 7 to 10%. When the enzymic cAMP method was compared with a radioimmunological procedure, the correlation coefficient was found to be 0.98."} {"id": "PMID:179128", "title": "Effect of streptozocin on gastrin release.", "content": "As streptozocin has a toxic effect on gastrin producing cells in some patients with gastrinomas, the action of the drug upon normal gastrin release was evaluated in patients with carcinoid tumours (n=6) and malignant insulinomas (n=2). No acute effects were recorded in 22 instances where gastrin levels were followed during the first 24 hours after infusion of streptozocin. When gastrin levels were compared throughout a course of repeated infusions during months a significant increase was noted. Concentrations were doubled after 6 g streptozocin given during a four months period, and tripled after 10 g in nine months period. One patients developed bleeding duodenal ulcer after a total dose of 6 g. It is concluded that streptozocin does not damage normal G cells, but by some action seems to stimulate gastrin relase. Peptic ulceration may be an important side effect during a long term treatment.", "contents": "Effect of streptozocin on gastrin release. As streptozocin has a toxic effect on gastrin producing cells in some patients with gastrinomas, the action of the drug upon normal gastrin release was evaluated in patients with carcinoid tumours (n=6) and malignant insulinomas (n=2). No acute effects were recorded in 22 instances where gastrin levels were followed during the first 24 hours after infusion of streptozocin. When gastrin levels were compared throughout a course of repeated infusions during months a significant increase was noted. Concentrations were doubled after 6 g streptozocin given during a four months period, and tripled after 10 g in nine months period. One patients developed bleeding duodenal ulcer after a total dose of 6 g. It is concluded that streptozocin does not damage normal G cells, but by some action seems to stimulate gastrin relase. Peptic ulceration may be an important side effect during a long term treatment."} {"id": "PMID:179129", "title": "Multiple vacuoles formation in erythroblasts in an erythroleukaemic patient.", "content": "Peculiar erythroblasts with multiple vacuoles were observed in the bone marrow of an erythroleukaemic patient. Some erythroblasts contained more than 80 vacuoles on a thin section. The contents of vacuoles were amorphous with low electron density. No transitional form from mitochondria or other organelles was observed. Since these vacuolated erythroblasts were clearly distinguishable from megaloblastoid erythraemia cells, multiple vacuoles formation is presumably attributable to the disturbance of microconnection net work in the normal red cell series.", "contents": "Multiple vacuoles formation in erythroblasts in an erythroleukaemic patient. Peculiar erythroblasts with multiple vacuoles were observed in the bone marrow of an erythroleukaemic patient. Some erythroblasts contained more than 80 vacuoles on a thin section. The contents of vacuoles were amorphous with low electron density. No transitional form from mitochondria or other organelles was observed. Since these vacuolated erythroblasts were clearly distinguishable from megaloblastoid erythraemia cells, multiple vacuoles formation is presumably attributable to the disturbance of microconnection net work in the normal red cell series."} {"id": "PMID:179130", "title": "mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. I. Clinical aspects.", "content": "A 27-year-old woman with proteinuria and normal serum creatinine for 10 years developed chronic lymphocytic leukaemia (CLL) and after further 2 years during treatment with prednisone and chlorambucil a malignant histiocytoma appeared. Free mu-chains were demonstrated in serum, but it is possible that mu-chain disease (mu-CD) and Bence-Jones proteinuria had persisted unrecognized for 12 years, since vacuolated plasma cells were found when the primary bone marrow smear was re-evaluated and no glomerular disorders were found. The clinical findings from the now 11 known cases of mu-CD are reveiwed and the immunochemical findings are reported ain part II (Axelsen et al 1976). The patient's mother died of acute leukaemia at the age of 24. The mother's sister has mammary carcinoma and several members of the mother's line apparently have increased tendency to infections. Of 27 family members, none exhibited immunoglobulin defects, but 10 members of the mother's line had B- as well as T-lymphocytosis and 5 members had leukocytosis.", "contents": "mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. I. Clinical aspects. A 27-year-old woman with proteinuria and normal serum creatinine for 10 years developed chronic lymphocytic leukaemia (CLL) and after further 2 years during treatment with prednisone and chlorambucil a malignant histiocytoma appeared. Free mu-chains were demonstrated in serum, but it is possible that mu-chain disease (mu-CD) and Bence-Jones proteinuria had persisted unrecognized for 12 years, since vacuolated plasma cells were found when the primary bone marrow smear was re-evaluated and no glomerular disorders were found. The clinical findings from the now 11 known cases of mu-CD are reveiwed and the immunochemical findings are reported ain part II (Axelsen et al 1976). The patient's mother died of acute leukaemia at the age of 24. The mother's sister has mammary carcinoma and several members of the mother's line apparently have increased tendency to infections. Of 27 family members, none exhibited immunoglobulin defects, but 10 members of the mother's line had B- as well as T-lymphocytosis and 5 members had leukocytosis."} {"id": "PMID:179131", "title": "Mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. II. Immunochemical studies.", "content": "Agarose gel electrophoresis of serum from the eleventh case of mu-chain disease (mu-CD) showed two distinct abnormal bands due to free light chains and kappa-complexes with other serum proteins. This caused diagnostic difficulties on conventional immunoelectrophoresis, and crossed immunoelectrophoresis with intermediate gel is demonstrated as a superior tool for investigation of mu-CD. A simple rocket immunoelectrophoresis method foe mu-CD screening is also shown. The mu-CD protein had alpha-2-mobility and a part of the protein carried kappa-determinants probably due to secondary binding. Preparative ultracentrifugation and size chromatography on serum demonstrated that the mu-CD protein was present in serum in several sizes, the smallest being a dimer of mu-chains. Due to scarcity of material the abnormal protein could not be characterized further.", "contents": "Mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. II. Immunochemical studies. Agarose gel electrophoresis of serum from the eleventh case of mu-chain disease (mu-CD) showed two distinct abnormal bands due to free light chains and kappa-complexes with other serum proteins. This caused diagnostic difficulties on conventional immunoelectrophoresis, and crossed immunoelectrophoresis with intermediate gel is demonstrated as a superior tool for investigation of mu-CD. A simple rocket immunoelectrophoresis method foe mu-CD screening is also shown. The mu-CD protein had alpha-2-mobility and a part of the protein carried kappa-determinants probably due to secondary binding. Preparative ultracentrifugation and size chromatography on serum demonstrated that the mu-CD protein was present in serum in several sizes, the smallest being a dimer of mu-chains. Due to scarcity of material the abnormal protein could not be characterized further."} {"id": "PMID:179134", "title": "A health survey of granite workers in Finland: radiographic findings, respiratory function, hearing, electric sensory thresholds of the fingers and subjective symptoms.", "content": "Results from a health survey of 777 granite workers, exposed to quartz dust, noise and/or machine vibration, and 122 unexposed \"controls\" are reported. The survey included chest X-rays, pulmonary function tests, a hearing examination, the determination of the electric sensory thresholds of the fingers, and questionnaires on the subjective symptoms of the respiratory system and upper limbs. The exposed workers' radiographic findings (except for a 2.6 % rate of silicosis), respiratory functions, and sensory thresholds did not differ significantly from those of the controls. Granite drillers had a high prevalence of hearing defects. Respiratory symptoms were common among drillers and sandblasters, and subjective symptoms of the upper limbs due to vibration occurred among the granite dressing workers who used pneumatic hammers. Both primary and secondary measures of prevention are strongly recommended for the granite industry, primarlily for quartz dust exposure and its health effects.", "contents": "A health survey of granite workers in Finland: radiographic findings, respiratory function, hearing, electric sensory thresholds of the fingers and subjective symptoms. Results from a health survey of 777 granite workers, exposed to quartz dust, noise and/or machine vibration, and 122 unexposed \"controls\" are reported. The survey included chest X-rays, pulmonary function tests, a hearing examination, the determination of the electric sensory thresholds of the fingers, and questionnaires on the subjective symptoms of the respiratory system and upper limbs. The exposed workers' radiographic findings (except for a 2.6 % rate of silicosis), respiratory functions, and sensory thresholds did not differ significantly from those of the controls. Granite drillers had a high prevalence of hearing defects. Respiratory symptoms were common among drillers and sandblasters, and subjective symptoms of the upper limbs due to vibration occurred among the granite dressing workers who used pneumatic hammers. Both primary and secondary measures of prevention are strongly recommended for the granite industry, primarlily for quartz dust exposure and its health effects."} {"id": "PMID:179135", "title": "Dissolution of silicic acid from amosite and quartz dusts under physiological conditions.", "content": "The dissolution of silica from amosite dust in human serum and in Ringer buffer at 37 degrees C was found to be significantly higher than that from quartz. The significance of this finding in relation to their fibrogenic effects has been discussed.", "contents": "Dissolution of silicic acid from amosite and quartz dusts under physiological conditions. The dissolution of silica from amosite dust in human serum and in Ringer buffer at 37 degrees C was found to be significantly higher than that from quartz. The significance of this finding in relation to their fibrogenic effects has been discussed."} {"id": "PMID:179136", "title": "[Cystosarcoma phylloides of the breast. Analysis of 58 cases].", "content": "Cystosarcoma phylloides (c.p.) is a rare fibroepithelial neoplasm of the mammary gland exhibiting considerable histological variations ranging from the aspect of hypercellular fibroadenoma to that of pleomorphic sarcoma. In this study, 58 cases of c.p. were graded according to their histology into 3 groups of increasing malignancy-benign tumors: 23 cases (42%), borderline tumors: 16 cases (27%) and malignant tumors: 18 cases (31%). Their clinical properties and evolution have been compared. These tumors were found exclusively in women, most often during the 5th and 6th decade of life (age range from 19 to 81 years). In two thirds of the cases, the history of the disease was shorter than 6 months. The symptoms were generally scant. Only in 2 cases were severe local lesions observed. The postoperative clinical course has been followed for at least 5 years in 32 instances. Recurrences were observed in 5 patients, the histology being as a rule the same as that of the primary tumor. The 12 patients with benign tumors are well 5 years or more after operation. One of the patients presenting a malignant tumor died of lung embolism soon after mastectomy. 2 out of 10 patients with borderline tumors died within 6 years with metastases of the mammary tumor. Our analysis confirms the experience that c.p. are relatively benign but often recurring neoplasms that rarely disseminate. As far as prognosis and treatment are concerned, tumors of questionable dignity should be considered malignant. To avoid such vague terms as \"benign or malignant c.p.\" we support OBERMANN'S suggested separation of c.p. into \"cellular fibroadenoma\" and \"periductal fribrosarcoma\". Wide local excision for small and benign tumors is recommended. All other forms require simple mastectomy. Prophylactic dissection of the axillary lymph nodes is not necessary as these tumors usually disseminate hematogenously. Roentgen therapy or chemotherapeutic agents are not useful in treatment.", "contents": "[Cystosarcoma phylloides of the breast. Analysis of 58 cases]. Cystosarcoma phylloides (c.p.) is a rare fibroepithelial neoplasm of the mammary gland exhibiting considerable histological variations ranging from the aspect of hypercellular fibroadenoma to that of pleomorphic sarcoma. In this study, 58 cases of c.p. were graded according to their histology into 3 groups of increasing malignancy-benign tumors: 23 cases (42%), borderline tumors: 16 cases (27%) and malignant tumors: 18 cases (31%). Their clinical properties and evolution have been compared. These tumors were found exclusively in women, most often during the 5th and 6th decade of life (age range from 19 to 81 years). In two thirds of the cases, the history of the disease was shorter than 6 months. The symptoms were generally scant. Only in 2 cases were severe local lesions observed. The postoperative clinical course has been followed for at least 5 years in 32 instances. Recurrences were observed in 5 patients, the histology being as a rule the same as that of the primary tumor. The 12 patients with benign tumors are well 5 years or more after operation. One of the patients presenting a malignant tumor died of lung embolism soon after mastectomy. 2 out of 10 patients with borderline tumors died within 6 years with metastases of the mammary tumor. Our analysis confirms the experience that c.p. are relatively benign but often recurring neoplasms that rarely disseminate. As far as prognosis and treatment are concerned, tumors of questionable dignity should be considered malignant. To avoid such vague terms as \"benign or malignant c.p.\" we support OBERMANN'S suggested separation of c.p. into \"cellular fibroadenoma\" and \"periductal fribrosarcoma\". Wide local excision for small and benign tumors is recommended. All other forms require simple mastectomy. Prophylactic dissection of the axillary lymph nodes is not necessary as these tumors usually disseminate hematogenously. Roentgen therapy or chemotherapeutic agents are not useful in treatment."} {"id": "PMID:179137", "title": "[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors].", "content": "The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress.", "contents": "[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress."} {"id": "PMID:179138", "title": "Characterization of the androgen receptor from a Syrian hamster ductus deferens tumor cell line (DDT1).", "content": "The hamster ductus deferens cloned tumor cell line (DDT1) contains a complex steroid receptor protein that binds 3H-labeled 5 alpha-dihydrotestosterone,. Diethylaminoethyl (DEAE) chromatography of cytosol from these cells yields two major receptor peaks of activity. Identification of this steroid binding protein as a cytoplasmic receptor was confirmed by salt dissociation on sucrose gradients, stability of the hormone-receptor complex at 0 degrees C, and the retention patterns on phosphocellulose and DEAE cellulose. Multiple forms of the receptor exist in a single homogeneous cell type. The data support the theory that steroid hormones bind to a cytoplasmic protein receptor composed of dissimilar subunits as the initial step in steroid hormone action.", "contents": "Characterization of the androgen receptor from a Syrian hamster ductus deferens tumor cell line (DDT1). The hamster ductus deferens cloned tumor cell line (DDT1) contains a complex steroid receptor protein that binds 3H-labeled 5 alpha-dihydrotestosterone,. Diethylaminoethyl (DEAE) chromatography of cytosol from these cells yields two major receptor peaks of activity. Identification of this steroid binding protein as a cytoplasmic receptor was confirmed by salt dissociation on sucrose gradients, stability of the hormone-receptor complex at 0 degrees C, and the retention patterns on phosphocellulose and DEAE cellulose. Multiple forms of the receptor exist in a single homogeneous cell type. The data support the theory that steroid hormones bind to a cytoplasmic protein receptor composed of dissimilar subunits as the initial step in steroid hormone action."} {"id": "PMID:179139", "title": "Neural properties of cultured human endocrine tumor cells of proposed neural crest origin.", "content": "Cells from human endocrine tumors of proposed neural crest origin--five pheochromocytomas, two medullary carcinomas of the thyroid, and two bronchial carcinoids--were grown in monolayer culture. Cells from all nine tumors, including epithelial forms of medullary carcinoma of the thyroid and bronchial carcinoid cells, and epithelial and neuron-like pheochromocytoma cells demonstrated all-or-nothing, short-duration action potentials.", "contents": "Neural properties of cultured human endocrine tumor cells of proposed neural crest origin. Cells from human endocrine tumors of proposed neural crest origin--five pheochromocytomas, two medullary carcinomas of the thyroid, and two bronchial carcinoids--were grown in monolayer culture. Cells from all nine tumors, including epithelial forms of medullary carcinoma of the thyroid and bronchial carcinoid cells, and epithelial and neuron-like pheochromocytoma cells demonstrated all-or-nothing, short-duration action potentials."} {"id": "PMID:179141", "title": "Bovine leukemia virus genes in the DNA of leukemic cattle.", "content": "Reverse transcripts of the rna genome of the bovine leukemia virus (BLV) as well as 125I-labeled BLV RNA hybridize to the DNA of tissues from leukemic cattle with the adult form of the disease but not to bovine thymic lymphoma or normal bovine tissues.", "contents": "Bovine leukemia virus genes in the DNA of leukemic cattle. Reverse transcripts of the rna genome of the bovine leukemia virus (BLV) as well as 125I-labeled BLV RNA hybridize to the DNA of tissues from leukemic cattle with the adult form of the disease but not to bovine thymic lymphoma or normal bovine tissues."} {"id": "PMID:179142", "title": "Ion-exchange in melanin: an electron spin resonance study with lanthanide probes.", "content": "Changes are induced in the electron spin resonance signal amplitude and microwave power saturation of the naturally occurring free radical in melanin by bound paramagnetic ions. The changes serve as experimental observables in competition experiments between diamagnetic and paramagnetic metal ions for melanin binding sites and between melanin and ethylenediaminetetraacetic acid for paramagnetic metal ions. Evidence is presented for the existence of several specific types of metal binding sites. The interaction of copper with free radicals leading to loss of electron spin resonance signal amplitude is magnetic in nature and not, as has been supposed, chemical.", "contents": "Ion-exchange in melanin: an electron spin resonance study with lanthanide probes. Changes are induced in the electron spin resonance signal amplitude and microwave power saturation of the naturally occurring free radical in melanin by bound paramagnetic ions. The changes serve as experimental observables in competition experiments between diamagnetic and paramagnetic metal ions for melanin binding sites and between melanin and ethylenediaminetetraacetic acid for paramagnetic metal ions. Evidence is presented for the existence of several specific types of metal binding sites. The interaction of copper with free radicals leading to loss of electron spin resonance signal amplitude is magnetic in nature and not, as has been supposed, chemical."} {"id": "PMID:179143", "title": "Oncogenic transformation of human embryo lung cells by human cytomegalovirus.", "content": "Persistent infection of human embryo lung fibroblasts with a genital isolate of cytomegalovirus resulted in oncogenic transformation of these cells. Immunofluorescence techniques detected virus-specific antigens, while microcytotoxicity tests established that the transformed cells share a membrane antigen with hamster cells transformed by inactivated cytomegalovirus. The transformed human cells induced progressively growing tumors in weanling athymic nude mice.", "contents": "Oncogenic transformation of human embryo lung cells by human cytomegalovirus. Persistent infection of human embryo lung fibroblasts with a genital isolate of cytomegalovirus resulted in oncogenic transformation of these cells. Immunofluorescence techniques detected virus-specific antigens, while microcytotoxicity tests established that the transformed cells share a membrane antigen with hamster cells transformed by inactivated cytomegalovirus. The transformed human cells induced progressively growing tumors in weanling athymic nude mice."} {"id": "PMID:179144", "title": "Increased sarcoma virus RNA in cells transformed by leukemia viruses: model for leukemogenesis.", "content": "A morphologically flat revertant of mink cells nonproductively infected with Moloney sarcoma virus exhibited contact inhibition and lacked detectable sarcoma virus RNA. Superinfection by usually nontransforming type C mammalian leukemia-causing viruses induced transformation and increased sarcoma virus RNA. The results suggest a model for leukemogenesis in animals by increasing, during replication of usually nontransforming leukemia viruses, the levels of RNA from potentially oncogenic cell or integrated virus transforming genes.", "contents": "Increased sarcoma virus RNA in cells transformed by leukemia viruses: model for leukemogenesis. A morphologically flat revertant of mink cells nonproductively infected with Moloney sarcoma virus exhibited contact inhibition and lacked detectable sarcoma virus RNA. Superinfection by usually nontransforming type C mammalian leukemia-causing viruses induced transformation and increased sarcoma virus RNA. The results suggest a model for leukemogenesis in animals by increasing, during replication of usually nontransforming leukemia viruses, the levels of RNA from potentially oncogenic cell or integrated virus transforming genes."} {"id": "PMID:179146", "title": "Lethal interaction of ubiquitous insecticide carriers with virus.", "content": "Large quantities of presumably nontoxic petroleum oil by-products are introduced into the environment as pesticide dispersal agents and emulsifiers. An increase in viral lethality with a concomitant influence on the liver and central nervous system occurs in young mice previously primed with such chemicals.", "contents": "Lethal interaction of ubiquitous insecticide carriers with virus. Large quantities of presumably nontoxic petroleum oil by-products are introduced into the environment as pesticide dispersal agents and emulsifiers. An increase in viral lethality with a concomitant influence on the liver and central nervous system occurs in young mice previously primed with such chemicals."} {"id": "PMID:179148", "title": "Diagnosis of infectious mononucleosis.", "content": "Infectious mononucleosis continues to be an important medical problem of young adults. Diagnosis is based on three principal criteria: (1) a compatible clinical picture, (2) characteristic hematologic changes, and (3) a positive serology. A relative lymphocytosis of 60% or higher with at least 20% atypical lymphocytes is a common feature. Laboratory diagnosis is dependent on proper application and interpretation of the various serologic tests. Evidence of abnormal liver function is of particular value in differentiating this disease from bacterial and viral pharyngitis.", "contents": "Diagnosis of infectious mononucleosis. Infectious mononucleosis continues to be an important medical problem of young adults. Diagnosis is based on three principal criteria: (1) a compatible clinical picture, (2) characteristic hematologic changes, and (3) a positive serology. A relative lymphocytosis of 60% or higher with at least 20% atypical lymphocytes is a common feature. Laboratory diagnosis is dependent on proper application and interpretation of the various serologic tests. Evidence of abnormal liver function is of particular value in differentiating this disease from bacterial and viral pharyngitis."} {"id": "PMID:179150", "title": "Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus.", "content": "Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing.", "contents": "Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus. Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing."} {"id": "PMID:179151", "title": "The prevalence of entamoeba histolytica and Toxoplasma gondii antibodies in Central Java, Indonesia.", "content": "Sera collected from people living along the slopes of Mt. Merapi and Mt. Merbabu (900-1900 m) in Boyolali Regency, Central Java, Indonesia were tested by indirect hemagglutination tests for antibodies to Entamoeba histolytica and Toxoplasma gondii. A total of 695 sera from 439 males and 256 females, 2 to 75 years of age were tested for amoebiasis and 17.6% had positive antibody titers of 1:128 or greater. The prevalence of antibodies was the same for males and females and increased with age. The seropositivity rate for Toxoplasma gondii antibodies among 438 males and 255 females was 2% at titers of 1:256 or greater. The prevalence was higher in females (2.7%) than in males (1.6%), and was highest in the oldest age groups.", "contents": "The prevalence of entamoeba histolytica and Toxoplasma gondii antibodies in Central Java, Indonesia. Sera collected from people living along the slopes of Mt. Merapi and Mt. Merbabu (900-1900 m) in Boyolali Regency, Central Java, Indonesia were tested by indirect hemagglutination tests for antibodies to Entamoeba histolytica and Toxoplasma gondii. A total of 695 sera from 439 males and 256 females, 2 to 75 years of age were tested for amoebiasis and 17.6% had positive antibody titers of 1:128 or greater. The prevalence of antibodies was the same for males and females and increased with age. The seropositivity rate for Toxoplasma gondii antibodies among 438 males and 255 females was 2% at titers of 1:256 or greater. The prevalence was higher in females (2.7%) than in males (1.6%), and was highest in the oldest age groups."} {"id": "PMID:179157", "title": "Radiation injury to abdominal aorta and iliac artery sustained in infancy.", "content": "Late complications of radiation therapy will become more common as treatment of neoplasms in childhood becomes more successful. A patient with a successfully treated Wilm's tumour presented with hypertension 3 years after therapy. Angiography revealed extensive damage to the aorta and left common iliac artery, probably caused by the radiation therapy. The hypertension was the result of renal artery stenosis.", "contents": "Radiation injury to abdominal aorta and iliac artery sustained in infancy. Late complications of radiation therapy will become more common as treatment of neoplasms in childhood becomes more successful. A patient with a successfully treated Wilm's tumour presented with hypertension 3 years after therapy. Angiography revealed extensive damage to the aorta and left common iliac artery, probably caused by the radiation therapy. The hypertension was the result of renal artery stenosis."} {"id": "PMID:179158", "title": "A site of action for zinc in neoplastic tissue.", "content": "The effect of dietary zinc levels on DNA synthesis in transplanted hepatomas induced by 3'-methyl-4-dimethyl-amino-azobenzene was investigated. DNA synthesis was found to be reduced (P less than 0,01) in rats maintained on diets low in zinc (0,5 mug/g) and high in zinc (less than 500 mug/g) when compared with the control animals given 60 mug zinc/g ration. Subsequently, the effect of dietary zinc intakes on the activity of 2 zinc-dependent enzymes associated with DNA synthesis--thymidine kinase and DNA polymerase--was studied. Both thymidine kinase and DNA polymerase activity was significantly reduced in animals receiving the zinc-deficient (0,5 mug/g) and zinc-supplemented (less than 500 mug/g) diets when compared with the control animals (60 mug/g). The data indicated that the DNA synthesis was the primary locus associated with zinc deficiency and zinc supplementation in proliferating tumour tissue, and that the site of action of zinc in this process was probably thymidine kinase, since there was considerable doubt concerning the role of DNA polymerase in DNA synthesis.", "contents": "A site of action for zinc in neoplastic tissue. The effect of dietary zinc levels on DNA synthesis in transplanted hepatomas induced by 3'-methyl-4-dimethyl-amino-azobenzene was investigated. DNA synthesis was found to be reduced (P less than 0,01) in rats maintained on diets low in zinc (0,5 mug/g) and high in zinc (less than 500 mug/g) when compared with the control animals given 60 mug zinc/g ration. Subsequently, the effect of dietary zinc intakes on the activity of 2 zinc-dependent enzymes associated with DNA synthesis--thymidine kinase and DNA polymerase--was studied. Both thymidine kinase and DNA polymerase activity was significantly reduced in animals receiving the zinc-deficient (0,5 mug/g) and zinc-supplemented (less than 500 mug/g) diets when compared with the control animals (60 mug/g). The data indicated that the DNA synthesis was the primary locus associated with zinc deficiency and zinc supplementation in proliferating tumour tissue, and that the site of action of zinc in this process was probably thymidine kinase, since there was considerable doubt concerning the role of DNA polymerase in DNA synthesis."} {"id": "PMID:179159", "title": "Collagenase and elastase released during peritonitis are complexed by plasma protease inhibitors.", "content": "Peritoneal fluids from patients with diffuse peritonitis secondary to perforation of the appendix contained large quantities of collagenase and elastase. The enzymes, which existed in the form of complexes with plasma protease inhibitors, probably had been released from the granulocytes. The two enzymes had linked almost half of the alpha 1-antitrypsin and four fifths of the alpha 2-macroglobulin in the fluid. Evidence that regional defense against protease had failed was obtained by finding the C3 component of complement completely converted. Toxic peptides probably had been released. Recognition of plasma protease inhibitors as an important part of the regional defense against protease also suggested use for therapy. We lavaged the peritoneum postoperatively with fluid that did not contain plasma inhibitors but with volumes large enough to eliminate the accumulation of enzymes for the granulocyte.", "contents": "Collagenase and elastase released during peritonitis are complexed by plasma protease inhibitors. Peritoneal fluids from patients with diffuse peritonitis secondary to perforation of the appendix contained large quantities of collagenase and elastase. The enzymes, which existed in the form of complexes with plasma protease inhibitors, probably had been released from the granulocytes. The two enzymes had linked almost half of the alpha 1-antitrypsin and four fifths of the alpha 2-macroglobulin in the fluid. Evidence that regional defense against protease had failed was obtained by finding the C3 component of complement completely converted. Toxic peptides probably had been released. Recognition of plasma protease inhibitors as an important part of the regional defense against protease also suggested use for therapy. We lavaged the peritoneum postoperatively with fluid that did not contain plasma inhibitors but with volumes large enough to eliminate the accumulation of enzymes for the granulocyte."} {"id": "PMID:179160", "title": "Metastatic potential of metastases.", "content": "Nine cases of known metastases originating from other metastatic foci were documented at operation. The primary tumors included four melanomas, two osteosarcomas, a synovial sarcoma, an anaplastic lung carcinoma, and a rhadbomyosarcoma. Secondary metastatic sites to the regional lymph nodes were noted in the pulmonary hilum (one), mediastinum (one), pulmonary hilum and mediastinum (three), small bowel mesentary (two), retroperitoneum (one), and axilla (one). All patients were immunocompetent as evidenced by their ability to be sensitized to 2,4-dinitrochlorobenzene (DNCB) and/or their positive response to common skin test antigens. The metastatic potential of cells from metastases does not appear to differ from cells of the primary.", "contents": "Metastatic potential of metastases. Nine cases of known metastases originating from other metastatic foci were documented at operation. The primary tumors included four melanomas, two osteosarcomas, a synovial sarcoma, an anaplastic lung carcinoma, and a rhadbomyosarcoma. Secondary metastatic sites to the regional lymph nodes were noted in the pulmonary hilum (one), mediastinum (one), pulmonary hilum and mediastinum (three), small bowel mesentary (two), retroperitoneum (one), and axilla (one). All patients were immunocompetent as evidenced by their ability to be sensitized to 2,4-dinitrochlorobenzene (DNCB) and/or their positive response to common skin test antigens. The metastatic potential of cells from metastases does not appear to differ from cells of the primary."} {"id": "PMID:179161", "title": "The effect of portacaval shunt on plasma lipids and tissue cholesterol synthesis in the dog.", "content": "Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet.", "contents": "The effect of portacaval shunt on plasma lipids and tissue cholesterol synthesis in the dog. Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet."} {"id": "PMID:179162", "title": "[The \"Vaccination Reaction\" syndrome of broilers after vaccination against Newcastle disease and infectious bronchitis (author's transl)].", "content": "In a part of the broiler flocks vaccinated against Newcastle disease (N.C.D) and infectious bronchitis (I.B.), disease symptoms of lingering nature have been observed, generally in the second half of the rearing period. In a practical investigation with weekly examinations of chickens, supplemented by a serological examination of twenty-four animals per flock at the age of six weeks, it was hoped to establish the factors responsible for this \"vaccination reaction\". In the district under notice the vaccination reaction syndrome had been responsible for widspread abandoning of twice spraying against N.C.D. in the first and fourth week in favour of drinking-water vaccination (generally combined with I.B. vaccination) in the second week and spray-vaccination in the fourth week or of combined drinking-water vaccination in the second week, either with or without N.C.D. drinking-water vaccination in the fourth week. Admittedly the incidence of vaccination reaction in flocks vaccinated exclusively via the drinking water was less frequent (32%) than in flocks in which the second vaccination was administered as a spray (48%), but this difference was largely accounted for by infection with Mycoplasma gallisepticum and/or Mycoplasma synoviae, complicated by infection with Escherichia coli. Of the thirty-three flocks free of mycoplasmosis, 24% exhibited the vaccination reaction, while the incidence to the fifteen infected flocks was 73.4%. In flocks infected with mycoplasmosis the course of E. coli infections was serious in 46.7% of the birds, while this figure was 18.2% in flocks free of mycoplasmosis. In flocks free of mycoplasmosis, the percentage of serious E. coli infections was lower after spray vaccination (14.3%) than after drinking-water vaccination (21%). The strains of E. coli brought in by one-day chicks from the hatchery disappear rapidly and play no role of any significance in the problem of colibacillosis observed at an age of three weeks or older. Of the 310 isolated strains of E. coli, 52 could not be typed and the others belonged to eighty different serotypes. With respect to the effect of infectious bronchitis the investigation does not provide sufficient evidence to permit of drawing conclusions. A significant role in the occurrence of the syndrome was played by coccidiosis and Gumboro's disease. With respect to environmental factors the available data did not allow of drawing conclusions. The authors recommend continuing with all available means to free the breeding animals from M. gallisepticum and M. synoviae, undertaking scientifically based research into the role of infectious bronchitis in the \"vaccination reaction\" syndrome, an effective programme of hygiene to control E...", "contents": "[The \"Vaccination Reaction\" syndrome of broilers after vaccination against Newcastle disease and infectious bronchitis (author's transl)]. In a part of the broiler flocks vaccinated against Newcastle disease (N.C.D) and infectious bronchitis (I.B.), disease symptoms of lingering nature have been observed, generally in the second half of the rearing period. In a practical investigation with weekly examinations of chickens, supplemented by a serological examination of twenty-four animals per flock at the age of six weeks, it was hoped to establish the factors responsible for this \"vaccination reaction\". In the district under notice the vaccination reaction syndrome had been responsible for widspread abandoning of twice spraying against N.C.D. in the first and fourth week in favour of drinking-water vaccination (generally combined with I.B. vaccination) in the second week and spray-vaccination in the fourth week or of combined drinking-water vaccination in the second week, either with or without N.C.D. drinking-water vaccination in the fourth week. Admittedly the incidence of vaccination reaction in flocks vaccinated exclusively via the drinking water was less frequent (32%) than in flocks in which the second vaccination was administered as a spray (48%), but this difference was largely accounted for by infection with Mycoplasma gallisepticum and/or Mycoplasma synoviae, complicated by infection with Escherichia coli. Of the thirty-three flocks free of mycoplasmosis, 24% exhibited the vaccination reaction, while the incidence to the fifteen infected flocks was 73.4%. In flocks infected with mycoplasmosis the course of E. coli infections was serious in 46.7% of the birds, while this figure was 18.2% in flocks free of mycoplasmosis. In flocks free of mycoplasmosis, the percentage of serious E. coli infections was lower after spray vaccination (14.3%) than after drinking-water vaccination (21%). The strains of E. coli brought in by one-day chicks from the hatchery disappear rapidly and play no role of any significance in the problem of colibacillosis observed at an age of three weeks or older. Of the 310 isolated strains of E. coli, 52 could not be typed and the others belonged to eighty different serotypes. With respect to the effect of infectious bronchitis the investigation does not provide sufficient evidence to permit of drawing conclusions. A significant role in the occurrence of the syndrome was played by coccidiosis and Gumboro's disease. With respect to environmental factors the available data did not allow of drawing conclusions. The authors recommend continuing with all available means to free the breeding animals from M. gallisepticum and M. synoviae, undertaking scientifically based research into the role of infectious bronchitis in the \"vaccination reaction\" syndrome, an effective programme of hygiene to control E..."} {"id": "PMID:179163", "title": "[Intrapulmonary fibromas (author's transl)].", "content": "Based on 5 individual cases over a period of 8 years (1 fibroma, 1 angiofibroma, 2 adenofibromas, 1 xanthous neurofibroma) the characteristics of the rare intrapulmonary fibroma and the therapeutic consequences are discussed. Any suspicious tumor demands a thoracotomy with careful preoperative treatment and the subsegment or segment resection depending on the histological diagnosis reported during the procedure.", "contents": "[Intrapulmonary fibromas (author's transl)]. Based on 5 individual cases over a period of 8 years (1 fibroma, 1 angiofibroma, 2 adenofibromas, 1 xanthous neurofibroma) the characteristics of the rare intrapulmonary fibroma and the therapeutic consequences are discussed. Any suspicious tumor demands a thoracotomy with careful preoperative treatment and the subsegment or segment resection depending on the histological diagnosis reported during the procedure."} {"id": "PMID:179166", "title": "[Therapeutic problems in the radiotherapy of bladder tumors].", "content": "The indications of different radiation techniques are reviewed. Out of these, the interstitial therapy should be regarded more attentively in future, unless too large a tumor is present in the fixed part of the bladder. The spatial distribution of the dose during percutaneous megavoltage therapy depends on the tumor stage. Irradiation is not allowed to be confined to the bladder except in case of primary findings corresponding to T1-2N0, the tumor being confined to the mucous or to the internal muscular tunica respectively, the degree of its malignancy being low and transitional cells having been revealed histologically. In all other cases, irradiation has to encompass the whole small pelvis. The split-course-technique has proved its value. If available, ultrahard bremsstrahlung is to be preferred. For radiation therapy of small volumes, fast electrons should be tested also in future.", "contents": "[Therapeutic problems in the radiotherapy of bladder tumors]. The indications of different radiation techniques are reviewed. Out of these, the interstitial therapy should be regarded more attentively in future, unless too large a tumor is present in the fixed part of the bladder. The spatial distribution of the dose during percutaneous megavoltage therapy depends on the tumor stage. Irradiation is not allowed to be confined to the bladder except in case of primary findings corresponding to T1-2N0, the tumor being confined to the mucous or to the internal muscular tunica respectively, the degree of its malignancy being low and transitional cells having been revealed histologically. In all other cases, irradiation has to encompass the whole small pelvis. The split-course-technique has proved its value. If available, ultrahard bremsstrahlung is to be preferred. For radiation therapy of small volumes, fast electrons should be tested also in future."} {"id": "PMID:179167", "title": "Characterization of the androgen receptors in the hypothalamus, preoptic area and brain cortex of the rat.", "content": "The specific androgen receptors for testosterone (T) (1) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the hypothalamus, preoptic area and brain cortex of the rat have been characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fractions in vivo and in vitro we were able to demonstrate androgen-receptor complexes moving with an electrophoretic mobility (R(f) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. Polyacrylamide gel electrophoresis was used as a quantitative assay for androgen receptors in the tissues. The hypothalamus, preoptic area and brain cortex were found to possess a single class of high affinity binding sites for androgens and the dissociation constants (K(D) were estimated to be 3.4, 4.3 and 2.6 X 10 (-10M) respectively. The binding capacities were 3.7 (hypothalamus), 3.5 (preoptic area) and 1.8 X 10 (-15) (brain cortex) moles of high affinity binding sites per mg protein. Like other androgen-receptor complexes, the testosterone-receptor complexes of the hypothalamus, preoptic area and brain cortex were temperature labile, sulfhydryl dependent and revealed a very slow rate of dissociation at o degrees C (t1/2 greater than 36 hr). The receptors in all the tissues had an isoelectric point of 5.8. The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for (3H)-testosterone binding. In the three tissues in investigation the following order of affinity was found: DHT greater than T greater than Cyproterone acetate greater than progesterone greater than androstenedione greater than 17beta-estradiol. Cortisol did not effect androgen binding significantly. Thus, the physiochemical characteristics of the cytoplasmic androgen receptors of the hypothalamus, preoptic area and brain cortex are very similar, if not identical, to those of the androgen receptors described in the anterior pituitary, ventral prostate, epididymis and testis.", "contents": "Characterization of the androgen receptors in the hypothalamus, preoptic area and brain cortex of the rat. The specific androgen receptors for testosterone (T) (1) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the hypothalamus, preoptic area and brain cortex of the rat have been characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fractions in vivo and in vitro we were able to demonstrate androgen-receptor complexes moving with an electrophoretic mobility (R(f) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. Polyacrylamide gel electrophoresis was used as a quantitative assay for androgen receptors in the tissues. The hypothalamus, preoptic area and brain cortex were found to possess a single class of high affinity binding sites for androgens and the dissociation constants (K(D) were estimated to be 3.4, 4.3 and 2.6 X 10 (-10M) respectively. The binding capacities were 3.7 (hypothalamus), 3.5 (preoptic area) and 1.8 X 10 (-15) (brain cortex) moles of high affinity binding sites per mg protein. Like other androgen-receptor complexes, the testosterone-receptor complexes of the hypothalamus, preoptic area and brain cortex were temperature labile, sulfhydryl dependent and revealed a very slow rate of dissociation at o degrees C (t1/2 greater than 36 hr). The receptors in all the tissues had an isoelectric point of 5.8. The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for (3H)-testosterone binding. In the three tissues in investigation the following order of affinity was found: DHT greater than T greater than Cyproterone acetate greater than progesterone greater than androstenedione greater than 17beta-estradiol. Cortisol did not effect androgen binding significantly. Thus, the physiochemical characteristics of the cytoplasmic androgen receptors of the hypothalamus, preoptic area and brain cortex are very similar, if not identical, to those of the androgen receptors described in the anterior pituitary, ventral prostate, epididymis and testis."} {"id": "PMID:179168", "title": "Effects of estrogen and testosterone on specific prolactin binding in the kidneys and adrenal of rats.", "content": "The effects of estradiol benzoate in the female rat, testosterone propionate in the male rat, and castration in both sexes on specific prolactin binding sites in the particulate membranes of the kidneys and adrenals were studied. Castration resulted in a significant increase in PRL binding activity in the kidneys of both males and females, and in a significant increase in PRL binding activity in the adrenals of the females. The increase in PRL binding with castration and the decrease seen with testosterone treatment were similar in both immature and mature rats. Progesterone administration to castrate females failed to alter PRL binding in both tissues. The present results suggest that estrogen and testosterone participate in the PRL osmoregulatory system in rat.", "contents": "Effects of estrogen and testosterone on specific prolactin binding in the kidneys and adrenal of rats. The effects of estradiol benzoate in the female rat, testosterone propionate in the male rat, and castration in both sexes on specific prolactin binding sites in the particulate membranes of the kidneys and adrenals were studied. Castration resulted in a significant increase in PRL binding activity in the kidneys of both males and females, and in a significant increase in PRL binding activity in the adrenals of the females. The increase in PRL binding with castration and the decrease seen with testosterone treatment were similar in both immature and mature rats. Progesterone administration to castrate females failed to alter PRL binding in both tissues. The present results suggest that estrogen and testosterone participate in the PRL osmoregulatory system in rat."} {"id": "PMID:179169", "title": "Antibacterial activity of 15-azasteroids alone and in combination with antibiotics.", "content": "A new class of 15-azasteroid analogues has been synthesized and tested for antimicrobial activity. The compounds 1, 10, 11, 11a-tetrahydro-7-methoxy-11a-methyl-2H-naphth (1,2-g) indol (methoxyimine) and 1,10,11,11a-tetrahydro-11a-methyl-2H-naphth (1,2-g) indol-7-ol (hydroxyimine) inhibit the growth of Bacillus subtillis and Escherichia coli at concentrations as low as 10-5 M. Addition of either compound to the growth medium casued a rapid inhibition in the transport of radioactive glucose, uracil and several amino acids. The inhibition of growth and substrate transport was reversed following removl of the steroid from the medium. The evidence is consistent with a site of steroid action at the cell periphery. Combining the methoxyimine with polyor circulin at subinhibitory concentrations produced greatly enhanced antimicrobial activity against Pseudomonas fluorescens. Similar action was observed against B. subtilis when the azasteroid was combined with vancomycin or chloramphenicol. The inhibitory action of other antibiotics such as penicillin or erythromycin was not affected by addition of the test compound. The results suggest formation of a molecular complex between the azasteroid and antibiotic which is responsible for the enhanced biological activity.", "contents": "Antibacterial activity of 15-azasteroids alone and in combination with antibiotics. A new class of 15-azasteroid analogues has been synthesized and tested for antimicrobial activity. The compounds 1, 10, 11, 11a-tetrahydro-7-methoxy-11a-methyl-2H-naphth (1,2-g) indol (methoxyimine) and 1,10,11,11a-tetrahydro-11a-methyl-2H-naphth (1,2-g) indol-7-ol (hydroxyimine) inhibit the growth of Bacillus subtillis and Escherichia coli at concentrations as low as 10-5 M. Addition of either compound to the growth medium casued a rapid inhibition in the transport of radioactive glucose, uracil and several amino acids. The inhibition of growth and substrate transport was reversed following removl of the steroid from the medium. The evidence is consistent with a site of steroid action at the cell periphery. Combining the methoxyimine with polyor circulin at subinhibitory concentrations produced greatly enhanced antimicrobial activity against Pseudomonas fluorescens. Similar action was observed against B. subtilis when the azasteroid was combined with vancomycin or chloramphenicol. The inhibitory action of other antibiotics such as penicillin or erythromycin was not affected by addition of the test compound. The results suggest formation of a molecular complex between the azasteroid and antibiotic which is responsible for the enhanced biological activity."} {"id": "PMID:179171", "title": "Suppression of mixed lymphocyte response in mice bearing primary tumors induced by murine sarcoma virus.", "content": "Mixed lymphocyte culture (MLC) responses of spleen cells from mice bearing tumors induced by murine sarcoma virus of the Moloney type (MSV) against allogeneic spleen cells were found to be markedly depressed, as estimated by three parameters: lymphoblast counts, 3H-thymidine incorporation (TI), and cell-mediated lysis (CML). While all three parameters were definitely depressed in comparison to the normal controls, TI was depressed to a greater degree than lymphoblast counts and CML. MSV spleen cells also had a suppressive effect on the MLC responses of normal spleen cells in third party type of experiments. The cells mediating this effect were radioresistant non-T cells, which were removed by adherence columns and were inactivated by carrageenan. These data suggested that the supressor cells were macrophages. Serum from MSV tumor-bearing mice had a greater suppressive effect than did normal mouse serum. Both the suppressor cells and the suppressive serum factors may play an important role in the immunosuppression observed in tumor-bearing hosts.", "contents": "Suppression of mixed lymphocyte response in mice bearing primary tumors induced by murine sarcoma virus. Mixed lymphocyte culture (MLC) responses of spleen cells from mice bearing tumors induced by murine sarcoma virus of the Moloney type (MSV) against allogeneic spleen cells were found to be markedly depressed, as estimated by three parameters: lymphoblast counts, 3H-thymidine incorporation (TI), and cell-mediated lysis (CML). While all three parameters were definitely depressed in comparison to the normal controls, TI was depressed to a greater degree than lymphoblast counts and CML. MSV spleen cells also had a suppressive effect on the MLC responses of normal spleen cells in third party type of experiments. The cells mediating this effect were radioresistant non-T cells, which were removed by adherence columns and were inactivated by carrageenan. These data suggested that the supressor cells were macrophages. Serum from MSV tumor-bearing mice had a greater suppressive effect than did normal mouse serum. Both the suppressor cells and the suppressive serum factors may play an important role in the immunosuppression observed in tumor-bearing hosts."} {"id": "PMID:179177", "title": "Serum lipoprotein concentration and composition in healthy 50-year-old men.", "content": "The classification of hyperlipoproteinaemias (HLP) is based on arbitrary limits between \"normolipidaemia\" and \"hyperlipidaemia\". 92 randomly selected healthy 50-year-old men were studied regarding serum lipoprotein (LP) lipid composition to define limits for \"normality\". Cholesterol and triglyceride concentrations were determined and the individual ratios between cholesterol and triglycerides were calculated in the ultracentrifugally isolated LP density classes. A significant linear correlation between cholesterol and triglyceride concentrations was found in the very low density lipoproteins (VLDL) and low density lipoproteins (LDL) but not in the high density lipoproteins (HDL). When different percentile limits for LDL cholesterol and VLDL triglycerides were used as cut-off points for \"normality\" not only the absolute prevalence but also the relative frequency of different types of HLP was influenced. 26 overweight men studied separately showed significantly increased VLDL cholesterol and triglyceride levels with maintenance of the normal ratio cholesterol/triglycerides of this LP class compared with non-obese subjects. Three different kinds of \"extra bands\" were occasionally seen on agarose electrophoresis: a \"double pre-beta\" band in whole serum (3%), a \"sinking pre-beta\" band with density greater than 1.006 (17%) and a \"late pre-beta\" band in VLDL (22%). While \"sinking pre-beta\" is identical with Lp (a) LP the \"late pre-beta\" band probably represents a certain accumulation of \"intermediary particles\".", "contents": "Serum lipoprotein concentration and composition in healthy 50-year-old men. The classification of hyperlipoproteinaemias (HLP) is based on arbitrary limits between \"normolipidaemia\" and \"hyperlipidaemia\". 92 randomly selected healthy 50-year-old men were studied regarding serum lipoprotein (LP) lipid composition to define limits for \"normality\". Cholesterol and triglyceride concentrations were determined and the individual ratios between cholesterol and triglycerides were calculated in the ultracentrifugally isolated LP density classes. A significant linear correlation between cholesterol and triglyceride concentrations was found in the very low density lipoproteins (VLDL) and low density lipoproteins (LDL) but not in the high density lipoproteins (HDL). When different percentile limits for LDL cholesterol and VLDL triglycerides were used as cut-off points for \"normality\" not only the absolute prevalence but also the relative frequency of different types of HLP was influenced. 26 overweight men studied separately showed significantly increased VLDL cholesterol and triglyceride levels with maintenance of the normal ratio cholesterol/triglycerides of this LP class compared with non-obese subjects. Three different kinds of \"extra bands\" were occasionally seen on agarose electrophoresis: a \"double pre-beta\" band in whole serum (3%), a \"sinking pre-beta\" band with density greater than 1.006 (17%) and a \"late pre-beta\" band in VLDL (22%). While \"sinking pre-beta\" is identical with Lp (a) LP the \"late pre-beta\" band probably represents a certain accumulation of \"intermediary particles\"."} {"id": "PMID:179172", "title": "[Bilateral tumors of the parotid glands. (author's transl)].", "content": "Bilateral parotid tumors occur very rarely; they account for 0.5% of 544 cases of parotid tumors recorded at the National Cancer Institute of Milan from 1945 to 1974. Three cases of bilateral tumors are described; two tumors were synchronous and one metachronous. The patients were women of 51, 46 and 52 years. The histologic type was the same on both sides in all cases, namely adenolymphoma, mucoepidermoid carcinoma and mixed tumor respectively. Surgical exicston was the treatment of choice; according to the histology of the tumors partial (adenolymphoma) or total parotidectomy (mixed and malignant tumors) was performed. As to the case of mucoepidermoid cancer of both parotid glands no recurrence was observed after five years.", "contents": "[Bilateral tumors of the parotid glands. (author's transl)]. Bilateral parotid tumors occur very rarely; they account for 0.5% of 544 cases of parotid tumors recorded at the National Cancer Institute of Milan from 1945 to 1974. Three cases of bilateral tumors are described; two tumors were synchronous and one metachronous. The patients were women of 51, 46 and 52 years. The histologic type was the same on both sides in all cases, namely adenolymphoma, mucoepidermoid carcinoma and mixed tumor respectively. Surgical exicston was the treatment of choice; according to the histology of the tumors partial (adenolymphoma) or total parotidectomy (mixed and malignant tumors) was performed. As to the case of mucoepidermoid cancer of both parotid glands no recurrence was observed after five years."} {"id": "PMID:179178", "title": "Herpesvirus type 2: isolation from seminal vesicle and testes.", "content": "Reproductive tissues from 10 recent male cadavers were examined. Herpesvirus type 2 was isolated from testes, seminal vesicle, or both in 4 cases. This is the first report of the isolation of herpesvirus type 2 from human seminal vesicular tissue. The data support previous evidence that herpesvirus type 2 can be isolated from the reproductive tissues of males without active or prior infection and suggest that these tissues may serve as a reservoir for transmission of this virus. The study also documents, for the first time, the ability to culture herpesvirus type 2 in organ explants from cadaveric reproductive tissues with the subsequent release of infectious virus.", "contents": "Herpesvirus type 2: isolation from seminal vesicle and testes. Reproductive tissues from 10 recent male cadavers were examined. Herpesvirus type 2 was isolated from testes, seminal vesicle, or both in 4 cases. This is the first report of the isolation of herpesvirus type 2 from human seminal vesicular tissue. The data support previous evidence that herpesvirus type 2 can be isolated from the reproductive tissues of males without active or prior infection and suggest that these tissues may serve as a reservoir for transmission of this virus. The study also documents, for the first time, the ability to culture herpesvirus type 2 in organ explants from cadaveric reproductive tissues with the subsequent release of infectious virus."} {"id": "PMID:179183", "title": "The isolation and some biological properties of a variant avian infectious bronchitis virus.", "content": "A virus isolated from a respiratory disease in chickens was identified as infectious bronchitis virus (IBV). By serum neutralisation tests the virus was shown to be serologically distinct from the Massachusetts type but to possess a one-way relationship with the Connecticut type. Experimentally, it caused a relatively mild respiratory disease in baby chicks. Vaccination of young chicks with H-120 Massachusetts IBV vaccine afforded a high degree of protection against challenge with the isolate. Some problems relating to the isolation and classification of field strains of IBV are briefly discussed.", "contents": "The isolation and some biological properties of a variant avian infectious bronchitis virus. A virus isolated from a respiratory disease in chickens was identified as infectious bronchitis virus (IBV). By serum neutralisation tests the virus was shown to be serologically distinct from the Massachusetts type but to possess a one-way relationship with the Connecticut type. Experimentally, it caused a relatively mild respiratory disease in baby chicks. Vaccination of young chicks with H-120 Massachusetts IBV vaccine afforded a high degree of protection against challenge with the isolate. Some problems relating to the isolation and classification of field strains of IBV are briefly discussed."} {"id": "PMID:179190", "title": "[Study of the pathogenic qualities of 4 celo-virus strains isolated in Bulgaria].", "content": "Four CELO virus strains, isolated in this country, were used to infect 3-day-old chicks via the trachea, muscularly, orally, subcutaneously, and cerebrally. The chicks were killed on the 2nd, 4th, 6th, 9th and 16th day following inoculation. Material was taken from each chick for morphologic, virologic, and serologic examination. The clinical course of the disease was also followed up. Prior to killing some birds showed infirmity, difficult breathing, slightly expressed diarrhia, going off food, and more sporadically there was fecal mass around the cloaca matting the plumage. Some manifested nervous symptoms similar to those observed in cases of Newcastle disease and encephalitis of birds. In some of the chicks there were hyperemia of the lungs, trachea, and intestins as well as necrotic foci in the liver.", "contents": "[Study of the pathogenic qualities of 4 celo-virus strains isolated in Bulgaria]. Four CELO virus strains, isolated in this country, were used to infect 3-day-old chicks via the trachea, muscularly, orally, subcutaneously, and cerebrally. The chicks were killed on the 2nd, 4th, 6th, 9th and 16th day following inoculation. Material was taken from each chick for morphologic, virologic, and serologic examination. The clinical course of the disease was also followed up. Prior to killing some birds showed infirmity, difficult breathing, slightly expressed diarrhia, going off food, and more sporadically there was fecal mass around the cloaca matting the plumage. Some manifested nervous symptoms similar to those observed in cases of Newcastle disease and encephalitis of birds. In some of the chicks there were hyperemia of the lungs, trachea, and intestins as well as necrotic foci in the liver."} {"id": "PMID:179191", "title": "[Study of the indirect complement fixation test for use in the differentiation of foot-and-mouth disease viruses and the determination of immunity].", "content": "Studies were carried out to establish the optimal conditions for the indirect complement-fixation test (ICFT) and explore the possibility to use the test in differentiating the foot-and-mouth disease (FMD) viruses and checking the immunity obtained in survivals or in animals that had been vaccinated against FMD. It was demonstrated that the proper use of ICFT necessitates in turn the use of a minimal amount of antigen, which in the presence of 1-2 E homologous hyperimmune serum completely binds the 1 E complement. Results showed that the sera of survived or vaccinated animals contain specific antibodies of titers of 1:4 up to 1:256. The latter depended on the type of vaccine, the amount of antigen in the vaccinal dose, and the time period from the immunization or survival up to the time of taking the serum samples. It is pointed out that ICFT is a sensitive and specific method for the differentiation of FMD viruses and the study of animals' immunity against FMD.", "contents": "[Study of the indirect complement fixation test for use in the differentiation of foot-and-mouth disease viruses and the determination of immunity]. Studies were carried out to establish the optimal conditions for the indirect complement-fixation test (ICFT) and explore the possibility to use the test in differentiating the foot-and-mouth disease (FMD) viruses and checking the immunity obtained in survivals or in animals that had been vaccinated against FMD. It was demonstrated that the proper use of ICFT necessitates in turn the use of a minimal amount of antigen, which in the presence of 1-2 E homologous hyperimmune serum completely binds the 1 E complement. Results showed that the sera of survived or vaccinated animals contain specific antibodies of titers of 1:4 up to 1:256. The latter depended on the type of vaccine, the amount of antigen in the vaccinal dose, and the time period from the immunization or survival up to the time of taking the serum samples. It is pointed out that ICFT is a sensitive and specific method for the differentiation of FMD viruses and the study of animals' immunity against FMD."} {"id": "PMID:179192", "title": "[Use of temperature, trypsin and biological tests for the intraspecies differentiation of local strains of Aujeszky's disease virus].", "content": "Studies were carried out with 8 strains of Aujeszky's disease virus using a temperature test (50 degrees C for 1 hour), a trypsin test (0.5 mg per cu. cm at 37 degrees C 1 hour), and a biologic test. The strains were isolated from the brain of dead pigs that have presumably been affected with encephalitis. They proved sensitive when studied with the temperature and the trypsin tests sharply lowering their titer. The viruses isolated from pneumonic foci in the lungs of pigs in which the disease had assumed a chronic course turned out to be considerably more resistant with the use of the two tests. The vaccinal strain MK was shown to be the most resistant in all tests. Comparable results were obtained also with the study of the viruses employing a modified test with young albino mice weighing 7-8 grams. The cerebral inoculation of the viruses aimed in this case at establishing the intracerebral pathogenetic index (IPI). Test rabbits were also used for the same purpose. The virulent strains had correspondingly a shorter incubation period and in rabbits there was a well pronounced clinical course, the IPI value being higher than 1.50. To latent viruses the rabbits responded with a protracted clinical course, and IPI ranged between 0.20 and 0.95.", "contents": "[Use of temperature, trypsin and biological tests for the intraspecies differentiation of local strains of Aujeszky's disease virus]. Studies were carried out with 8 strains of Aujeszky's disease virus using a temperature test (50 degrees C for 1 hour), a trypsin test (0.5 mg per cu. cm at 37 degrees C 1 hour), and a biologic test. The strains were isolated from the brain of dead pigs that have presumably been affected with encephalitis. They proved sensitive when studied with the temperature and the trypsin tests sharply lowering their titer. The viruses isolated from pneumonic foci in the lungs of pigs in which the disease had assumed a chronic course turned out to be considerably more resistant with the use of the two tests. The vaccinal strain MK was shown to be the most resistant in all tests. Comparable results were obtained also with the study of the viruses employing a modified test with young albino mice weighing 7-8 grams. The cerebral inoculation of the viruses aimed in this case at establishing the intracerebral pathogenetic index (IPI). Test rabbits were also used for the same purpose. The virulent strains had correspondingly a shorter incubation period and in rabbits there was a well pronounced clinical course, the IPI value being higher than 1.50. To latent viruses the rabbits responded with a protracted clinical course, and IPI ranged between 0.20 and 0.95."} {"id": "PMID:179193", "title": "[Hepatoma in artificially raised trout].", "content": "Cases were described of a hepatoma in the liver of trout, Salmo irideus, Gibb., originating from three fish-breeding farms in the district of Sofia. Histologically, three were tumor cells arranged in the form of trabeculae and paths or distributed focally. The tumorous growths had trabeculous, more rarely alveolar structure. Some of the neoplasms had carcinomatous character. The tumor stroma had weakly developed, however, in some parts three was rich fibrous stroma, and the gross appearance resembled fibroadenoma. Infiltrative growth was also observed. It is concluded that the hepatoma observed in poikilothermic animals (rainbow trout) is similar to the liver tumors found in birds and mammals.", "contents": "[Hepatoma in artificially raised trout]. Cases were described of a hepatoma in the liver of trout, Salmo irideus, Gibb., originating from three fish-breeding farms in the district of Sofia. Histologically, three were tumor cells arranged in the form of trabeculae and paths or distributed focally. The tumorous growths had trabeculous, more rarely alveolar structure. Some of the neoplasms had carcinomatous character. The tumor stroma had weakly developed, however, in some parts three was rich fibrous stroma, and the gross appearance resembled fibroadenoma. Infiltrative growth was also observed. It is concluded that the hepatoma observed in poikilothermic animals (rainbow trout) is similar to the liver tumors found in birds and mammals."} {"id": "PMID:179194", "title": "Multiple hepatocellular tumours in a patient treated with oral contraceptives.", "content": "A case of multiple hepatic tumours in a patient treated for four years with high doses of oral contraceptives is described. Solitary hepatocellular lesions associated with conventional doses of oral contraceptives have been reported previously in twenty nine cases. Haemorrhage has been a common mode of presentation and is attributed to the marked vascularity of the lesions, an appearance referred to as peliosis hepatis. Radiographic studies show this term to be inappropriate as the vessels are of arterial origin. Another finding not previously reported is the presence of diffuse hyperplasia in the non-tumourous parts of the liver.", "contents": "Multiple hepatocellular tumours in a patient treated with oral contraceptives. A case of multiple hepatic tumours in a patient treated for four years with high doses of oral contraceptives is described. Solitary hepatocellular lesions associated with conventional doses of oral contraceptives have been reported previously in twenty nine cases. Haemorrhage has been a common mode of presentation and is attributed to the marked vascularity of the lesions, an appearance referred to as peliosis hepatis. Radiographic studies show this term to be inappropriate as the vessels are of arterial origin. Another finding not previously reported is the presence of diffuse hyperplasia in the non-tumourous parts of the liver."} {"id": "PMID:179195", "title": "Ultrastructure of tubular inclusions in endothelial cells of pituitary tumors associated with acromegaly.", "content": "Tubular inclusions were present in 13 out of 43 pituitary adenomas of acromegalic patients and in a single chromophobe pituitary adenoma. There were none in 76 other pituitary adenomas with differing endocrinological symptomatology. The arrays were usually located in the perinuclear cistern of capillary endothelial cells. The tubule diameter in osmium fixed material measured 19-26 nm and the light core averaged 6-11 nm. A longitudinal period of about 4.5 nm could be demonstrated with PTA block staining. Fixation with glutaraldehyde and block staining with ethidium bromide as well as permanganate fixation followed by RNAse treatment showed only the core of the tubules consisting of globular subunits. Several histochemical reactions (perchloric acid extraction, methenamine-silver staining, trypsin and DNAse digestion of frozen sections) suggested that the particles consist of a core of DNA coated with protein. No virus multiplication could be detected in cell cultures or in mice innoculated with fresh tumor material. No significant antibody titers against several virus antigens could be demonstrated.", "contents": "Ultrastructure of tubular inclusions in endothelial cells of pituitary tumors associated with acromegaly. Tubular inclusions were present in 13 out of 43 pituitary adenomas of acromegalic patients and in a single chromophobe pituitary adenoma. There were none in 76 other pituitary adenomas with differing endocrinological symptomatology. The arrays were usually located in the perinuclear cistern of capillary endothelial cells. The tubule diameter in osmium fixed material measured 19-26 nm and the light core averaged 6-11 nm. A longitudinal period of about 4.5 nm could be demonstrated with PTA block staining. Fixation with glutaraldehyde and block staining with ethidium bromide as well as permanganate fixation followed by RNAse treatment showed only the core of the tubules consisting of globular subunits. Several histochemical reactions (perchloric acid extraction, methenamine-silver staining, trypsin and DNAse digestion of frozen sections) suggested that the particles consist of a core of DNA coated with protein. No virus multiplication could be detected in cell cultures or in mice innoculated with fresh tumor material. No significant antibody titers against several virus antigens could be demonstrated."} {"id": "PMID:179196", "title": "[Central giant cell granuloma: histochemical and ultrastructural study on its histogenesis (author's transl)].", "content": "Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods. Rather similar histochemical properties were shown in giant cells and pericytes of capillary sproute penetrating the granuloma. Cell fusion occurred between both cell types as was observed by electron microscopy. The process of cell fusion is defined by characteristic interdigitations of cell membranes. Therefore pericytes are believed to be the stem cells of multinucleated giant cells in giant cell granuloma. The abundance of giant cells usually occurring in the granuloma might be explained by plenty of capillary sprouts made up by clusters of pericytes. The factors inducing the pericytic cell fusion process are still unknown. The question arises whether cytogenesis of giant cells in giant cell granuloma might be similar in other giant cell lesions or even in the development of multinucleated osteoclasts.", "contents": "[Central giant cell granuloma: histochemical and ultrastructural study on its histogenesis (author's transl)]. Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods. Rather similar histochemical properties were shown in giant cells and pericytes of capillary sproute penetrating the granuloma. Cell fusion occurred between both cell types as was observed by electron microscopy. The process of cell fusion is defined by characteristic interdigitations of cell membranes. Therefore pericytes are believed to be the stem cells of multinucleated giant cells in giant cell granuloma. The abundance of giant cells usually occurring in the granuloma might be explained by plenty of capillary sprouts made up by clusters of pericytes. The factors inducing the pericytic cell fusion process are still unknown. The question arises whether cytogenesis of giant cells in giant cell granuloma might be similar in other giant cell lesions or even in the development of multinucleated osteoclasts."} {"id": "PMID:179197", "title": "Pituitary growth hormone and somatotrophs in rats bearing chemically induced hepatomas.", "content": "Measurement of pituitary growth hormone (GH) content by polyacrylamide gel electrophoresis (PAGE) showed that rats bearing diethylnitrosamine (DENA) induced hepatomas contained significantly less GH than age-related controls. Light microscopy of these pituitaries revealed many apparently dying somatotrophs in tumour bearing rats. By electron microscopy the somatotrophs of DENA hepatoma rats were relatively inactive and some clearly dying, which could account for the reduced hormone content. However, electron microscopy of somatotrophs of rats with 2-acetyl-aminofluorene (2-AAF) hepatic tumour nodules revealed many very active cells with greatly increased content of free ribosomes and many granules poised for imminent release. Other somatotrophs of these rats showed lysosomal activity indicating reduced secretion after an active phase.", "contents": "Pituitary growth hormone and somatotrophs in rats bearing chemically induced hepatomas. Measurement of pituitary growth hormone (GH) content by polyacrylamide gel electrophoresis (PAGE) showed that rats bearing diethylnitrosamine (DENA) induced hepatomas contained significantly less GH than age-related controls. Light microscopy of these pituitaries revealed many apparently dying somatotrophs in tumour bearing rats. By electron microscopy the somatotrophs of DENA hepatoma rats were relatively inactive and some clearly dying, which could account for the reduced hormone content. However, electron microscopy of somatotrophs of rats with 2-acetyl-aminofluorene (2-AAF) hepatic tumour nodules revealed many very active cells with greatly increased content of free ribosomes and many granules poised for imminent release. Other somatotrophs of these rats showed lysosomal activity indicating reduced secretion after an active phase."} {"id": "PMID:179212", "title": "[Correlation between immunological reactivity and the fat-carbohydrate metabolism. Influence of phenformin].", "content": "Based on the conceptions of the relationship between energy and adaptation-immunological systems a number of hormone-metabolic indices were compared with immune reactivity as evidenced by skin tests and rosette-formation reaction. It is shown that lowering of immunological indices in oncological patients is associated with a decreased sensitivity of dexametasone suppression of cortisol, an increased concentration of 11-oxycorticosteroids in blood, a higher level of triglycerides, cholestrol, beta-lipoproteins and less glucose tolerance. The use of phenformin during 3 months in patients with atherosclerosis resulted in a considerable increase of the index of phytohemagglutinin stimulated blasttransformation of lymphocytes and rosette-formation reaction. This effect was associated with normalization of lipid metabolism indices.", "contents": "[Correlation between immunological reactivity and the fat-carbohydrate metabolism. Influence of phenformin]. Based on the conceptions of the relationship between energy and adaptation-immunological systems a number of hormone-metabolic indices were compared with immune reactivity as evidenced by skin tests and rosette-formation reaction. It is shown that lowering of immunological indices in oncological patients is associated with a decreased sensitivity of dexametasone suppression of cortisol, an increased concentration of 11-oxycorticosteroids in blood, a higher level of triglycerides, cholestrol, beta-lipoproteins and less glucose tolerance. The use of phenformin during 3 months in patients with atherosclerosis resulted in a considerable increase of the index of phytohemagglutinin stimulated blasttransformation of lymphocytes and rosette-formation reaction. This effect was associated with normalization of lipid metabolism indices."} {"id": "PMID:179213", "title": "[Hematopoiesis in children with retroperitoneal neurogenic tumors].", "content": "Under observation were 140 children with retroperitoneal neurogenic tumors. In 69 of 125 patients with malignant neoplasms metastases were detected. Hemographic and myelographic findings were analysed depending on the degree of malignancy and tumor spread. Anemia usually moderate and normochromatic was observed only in neuroblastomas. This group of patients is also characterized by frequent shifts to the left leucograms and high sedimentation test, contrary to benigh tumors. The investigation of bone marrow allows one to reveal the suppression, and more rarely irritation of various blood stems.", "contents": "[Hematopoiesis in children with retroperitoneal neurogenic tumors]. Under observation were 140 children with retroperitoneal neurogenic tumors. In 69 of 125 patients with malignant neoplasms metastases were detected. Hemographic and myelographic findings were analysed depending on the degree of malignancy and tumor spread. Anemia usually moderate and normochromatic was observed only in neuroblastomas. This group of patients is also characterized by frequent shifts to the left leucograms and high sedimentation test, contrary to benigh tumors. The investigation of bone marrow allows one to reveal the suppression, and more rarely irritation of various blood stems."} {"id": "PMID:179220", "title": "[Scintigraphy of the pancreas in insuloma].", "content": "The results from the scintigraphic investigations of 28 patients are analyzed. In 11 o them-comparative observations are carried out between the scintigraphic and operative data, revealing a complete coincidence. Focal changes are predominantly observed in the scintigraphic image of pancreas-75 per cent in insuloma disease. Pancreas scintigraphy has a leading role in insuloma disease diagnosis.", "contents": "[Scintigraphy of the pancreas in insuloma]. The results from the scintigraphic investigations of 28 patients are analyzed. In 11 o them-comparative observations are carried out between the scintigraphic and operative data, revealing a complete coincidence. Focal changes are predominantly observed in the scintigraphic image of pancreas-75 per cent in insuloma disease. Pancreas scintigraphy has a leading role in insuloma disease diagnosis."} {"id": "PMID:179216", "title": "[Localization of genome RNA synthesis in Sendai virus].", "content": "Localization of Sendai virus 50S RNA in Ehrlich ascitic carcinoma cells was studied. At 48 hours postinfection virus-specific 50S RNA was found in the nucleus after 30 min exposure to 3H-uridine, and its amount increased after 1-hour exposure to the precursor reaching 18% of the total nucleus virus-specific RNA. After 2-hour or longer exposure to the precursor the amount of 50S RNA in the nuclei decreased considerably and in the cytoplasm in this gradient region a considerable radioactivity appeared. Rapid utilization of 3H-uridine by the cells under these experimental conditions suggests that 50S RNA is synthesized in the nucleus and migrates to the cytoplasm.", "contents": "[Localization of genome RNA synthesis in Sendai virus]. Localization of Sendai virus 50S RNA in Ehrlich ascitic carcinoma cells was studied. At 48 hours postinfection virus-specific 50S RNA was found in the nucleus after 30 min exposure to 3H-uridine, and its amount increased after 1-hour exposure to the precursor reaching 18% of the total nucleus virus-specific RNA. After 2-hour or longer exposure to the precursor the amount of 50S RNA in the nuclei decreased considerably and in the cytoplasm in this gradient region a considerable radioactivity appeared. Rapid utilization of 3H-uridine by the cells under these experimental conditions suggests that 50S RNA is synthesized in the nucleus and migrates to the cytoplasm."} {"id": "PMID:179217", "title": "[Generalized monkeypox in orally infected rabbits and white mice].", "content": "In the past 5 years 17 human cases of monkeypox with 4 deaths were reported in African countries. The source and the mechanism of transmission of the infection are unknown. One of the possible modes of human infection could be through monkey meat used for food. The paper presents the results of the study of susceptibility of 4 species of laboratory animals to monkeypox virus given orally. Adult rabbits, guinea pigs, and hamsters were found to be resistant. Ten-day-old rabbits and 8-, 10- and 12-day-old mice developed generalized infection with eruptions and high lethality. The infection was transmitted to uninfected rabbits of the same litter, apparently by air-borne droplet mode. The obtained model of generalized monkeypox infection after per os administration of the virus and the fact of air-borne droplet transmission of infection may serve as indirect evidence of the possibility of transmission of the infection by this mode in nature.", "contents": "[Generalized monkeypox in orally infected rabbits and white mice]. In the past 5 years 17 human cases of monkeypox with 4 deaths were reported in African countries. The source and the mechanism of transmission of the infection are unknown. One of the possible modes of human infection could be through monkey meat used for food. The paper presents the results of the study of susceptibility of 4 species of laboratory animals to monkeypox virus given orally. Adult rabbits, guinea pigs, and hamsters were found to be resistant. Ten-day-old rabbits and 8-, 10- and 12-day-old mice developed generalized infection with eruptions and high lethality. The infection was transmitted to uninfected rabbits of the same litter, apparently by air-borne droplet mode. The obtained model of generalized monkeypox infection after per os administration of the virus and the fact of air-borne droplet transmission of infection may serve as indirect evidence of the possibility of transmission of the infection by this mode in nature."} {"id": "PMID:179218", "title": "[Nature of membrane cellular antigens induced by avian leukosis-sarcoma viruses].", "content": "Using the immunofluorescent procedure and cross adsorption tests it was established that the common membrane cellular antigen coded for by avian sarcoma-leukemia virus genome could be found not only in Rous tumours of different animal classes but also in normal chick embryo cells after their propagation in vitro. The nature and function of the discovered antigen are discussed.", "contents": "[Nature of membrane cellular antigens induced by avian leukosis-sarcoma viruses]. Using the immunofluorescent procedure and cross adsorption tests it was established that the common membrane cellular antigen coded for by avian sarcoma-leukemia virus genome could be found not only in Rous tumours of different animal classes but also in normal chick embryo cells after their propagation in vitro. The nature and function of the discovered antigen are discussed."} {"id": "PMID:179223", "title": "[Cancer chemotherapy of inoperable bronchial carcinomas (author's transl)].", "content": "The nowadays' therapeutic results in bronchogenic cancer are rather poor. However, chemotherapy-promises some improvements in remission rates and survival. These results are achievable as well as by mono and by polychemotherapy. The current clinical studies are aimed at optimal application regimes of the drugs beeing at hand. Cyclophosphamide, Methotrexate and Adriamycin are the most effective drugs for montherapy. Alkylants and Methotrexate are especially effective in the oat cell carcinomas. Many cases seem to be more benefited by polychemotherapy than by monotherapy. However, a randomized clinical trial is presented which shows that a montherapy with Adriamycin gave the same results as polychemotherapy. In the case of bronchogenic carcinoma a simultaneously given polychemotherapy is more effective than a sequentially given one. Novel approaches aiming at further improvement of therapeutic results should more consider individual tumour-biological parameters of the tumour-host relationships and possbilities of pharmacological influences upon hemostasis, tumour vascularisation and immunological defense system.", "contents": "[Cancer chemotherapy of inoperable bronchial carcinomas (author's transl)]. The nowadays' therapeutic results in bronchogenic cancer are rather poor. However, chemotherapy-promises some improvements in remission rates and survival. These results are achievable as well as by mono and by polychemotherapy. The current clinical studies are aimed at optimal application regimes of the drugs beeing at hand. Cyclophosphamide, Methotrexate and Adriamycin are the most effective drugs for montherapy. Alkylants and Methotrexate are especially effective in the oat cell carcinomas. Many cases seem to be more benefited by polychemotherapy than by monotherapy. However, a randomized clinical trial is presented which shows that a montherapy with Adriamycin gave the same results as polychemotherapy. In the case of bronchogenic carcinoma a simultaneously given polychemotherapy is more effective than a sequentially given one. Novel approaches aiming at further improvement of therapeutic results should more consider individual tumour-biological parameters of the tumour-host relationships and possbilities of pharmacological influences upon hemostasis, tumour vascularisation and immunological defense system."} {"id": "PMID:179219", "title": "[Study of tissue culture herpes vaccine].", "content": "Features of propagation of 4 herpes simplex virus strains and their biological properties in the course of passages in chick embryo fibroblast cultures were studied. Investigations of experimental formalin-inactivated polyvaccine in animals and in trials in volunteers, patients with relapsing herpes, established its safety and sufficient effectiveness.", "contents": "[Study of tissue culture herpes vaccine]. Features of propagation of 4 herpes simplex virus strains and their biological properties in the course of passages in chick embryo fibroblast cultures were studied. Investigations of experimental formalin-inactivated polyvaccine in animals and in trials in volunteers, patients with relapsing herpes, established its safety and sufficient effectiveness."} {"id": "PMID:179224", "title": "[Cell-culture-tests (oncobiograms) in 105 bronchial carcinomas (author's transl)].", "content": "Thirty-six oncobiograms (cell culture tests) of bronchial carcinomas are reported. One hundred forty-eight single tests showed a predominant cytostatic sensibility of the different squamous cell carcinomas and alluded to a special effectiveness of the alkylating chemotherapeutical agents, so that the oncobiogram may be able at the same time to support the polychemotherapy to day discussed and realized in all special branches.", "contents": "[Cell-culture-tests (oncobiograms) in 105 bronchial carcinomas (author's transl)]. Thirty-six oncobiograms (cell culture tests) of bronchial carcinomas are reported. One hundred forty-eight single tests showed a predominant cytostatic sensibility of the different squamous cell carcinomas and alluded to a special effectiveness of the alkylating chemotherapeutical agents, so that the oncobiogram may be able at the same time to support the polychemotherapy to day discussed and realized in all special branches."} {"id": "PMID:179225", "title": "[Difficulties with diagnosis of intrathoracic neurogenic tumors (author's transl)].", "content": "58 patients have been operated for neurogenic tumors of the mediastinum. Diagnostic problems are discussed. Some rare cases are presented: a neurofibroma of the n. vagus with mediastinal localization, a cavernous hemangioma, a leiomyoma and a fibrosarcoma; all of these imitating typical neurogenic tumors. The patient with the fibrosarcoma had several operations for recurrence of the histologically benign neurofibroma and died 4 years later of generalized fibrosarcoma. Because of this possible histological error all seemingly benign neurogenic tumors should be removed early.", "contents": "[Difficulties with diagnosis of intrathoracic neurogenic tumors (author's transl)]. 58 patients have been operated for neurogenic tumors of the mediastinum. Diagnostic problems are discussed. Some rare cases are presented: a neurofibroma of the n. vagus with mediastinal localization, a cavernous hemangioma, a leiomyoma and a fibrosarcoma; all of these imitating typical neurogenic tumors. The patient with the fibrosarcoma had several operations for recurrence of the histologically benign neurofibroma and died 4 years later of generalized fibrosarcoma. Because of this possible histological error all seemingly benign neurogenic tumors should be removed early."} {"id": "PMID:179226", "title": "[Biologic factors and malignancy in mediastinal neoplasms (author's transl)].", "content": "The clinical and histological diagnosis of mediastinal tumors has to be completed with an appreciation of the biological relationship between the tumor and its host. This is most important for neurogenic and thymic tumors. Successful removal is sometimes possible even after a long time of observation. Auxillary use of radiation and cystostatics is recommended.", "contents": "[Biologic factors and malignancy in mediastinal neoplasms (author's transl)]. The clinical and histological diagnosis of mediastinal tumors has to be completed with an appreciation of the biological relationship between the tumor and its host. This is most important for neurogenic and thymic tumors. Successful removal is sometimes possible even after a long time of observation. Auxillary use of radiation and cystostatics is recommended."} {"id": "PMID:179227", "title": "[The reaction of the secretory elements of the mucosa of the upper respiratory tract from physiological and pathophysiological aspects (author's transl)].", "content": "The main function of the secretory elements of the mucosa of the upper respiratory tract - endoepithelial beaker cells and complex glands, exoepithelially situated - is surface defense. From this point of view ciliary system and secretion form a functional unit. Disorders of the synergism of the components may irreversible change the structure of the mucosa as demonstrated e.g. by the chronic forms of inflammation, when the limits of compensation are exceeded. The interrelation between epithelium and lamina propria are explained on the basis of histochemical evidence from normal and pathological mucosa of the upper respiratory tract. The metabolic processes between the vascular system and the cells form the basis of the normal as well as pathological secretion of the mucosa.", "contents": "[The reaction of the secretory elements of the mucosa of the upper respiratory tract from physiological and pathophysiological aspects (author's transl)]. The main function of the secretory elements of the mucosa of the upper respiratory tract - endoepithelial beaker cells and complex glands, exoepithelially situated - is surface defense. From this point of view ciliary system and secretion form a functional unit. Disorders of the synergism of the components may irreversible change the structure of the mucosa as demonstrated e.g. by the chronic forms of inflammation, when the limits of compensation are exceeded. The interrelation between epithelium and lamina propria are explained on the basis of histochemical evidence from normal and pathological mucosa of the upper respiratory tract. The metabolic processes between the vascular system and the cells form the basis of the normal as well as pathological secretion of the mucosa."} {"id": "PMID:179229", "title": "[Early IgM decrease in the serum of carcinoma patients with paraneoplastic skin manifestations].", "content": "The authors describe two patients suffering from cancer accompanied with paraneoplastic skin disorders (bullous pemphigoid, dermatomyositis). Before the diagnosis of stomach cancer was obtained by X-ray examination, the IgM-level was found lower than in normal persons. The value of the IgM-estimation in the serum seems to be high in the diagnosis of tumours. Other causes of the decreased IgM-level than tumours and paraneoplastic disorders of the skin were not found.", "contents": "[Early IgM decrease in the serum of carcinoma patients with paraneoplastic skin manifestations]. The authors describe two patients suffering from cancer accompanied with paraneoplastic skin disorders (bullous pemphigoid, dermatomyositis). Before the diagnosis of stomach cancer was obtained by X-ray examination, the IgM-level was found lower than in normal persons. The value of the IgM-estimation in the serum seems to be high in the diagnosis of tumours. Other causes of the decreased IgM-level than tumours and paraneoplastic disorders of the skin were not found."} {"id": "PMID:179231", "title": "[Results of treatment with the Herpes simplex antigen Lupidon H, resp. Lupidon G].", "content": "The results of treatment with LUPIDON achieved by 215 dermatologists with reference to a total number of 1059 cases are reported taking into account the controlled evaluation of questionnaires. Due to the considerable number of patients and physicians involved in this clinical investigation the presuppositions for objectiveness in respect of statistical evaluation were especially favourable. The results of treatment with LUPIDON--LUPIDON H and LUPIDON G proved to be of equal effectiveness--can be denoted as very positive because of the good or very good effects that could be observed in more than 80% of all the cases concerned. Such a therapeutically favourable result refers primarily to Herpes labialis, Herpes genitalis and Herpes eruptions infesting trunk and head; other types of herpes disease, for example Herpes glutealis or stomatitis aphthosa were only improved to about 60%. The compatability of LUPIDON was striking. The rate of side-effects was at 3%. Moreover, other series of data are given with the intention to inform about criteria such as: Frequency of localisations with regard to Herpes simplex diseases; distribution according to sex of patients being suffering from Herpes labialis and Herpes genitalis; distribution according to age; duration of Herpes simplex before starting a treatment with LUPIDON; accompanying skin diseases.", "contents": "[Results of treatment with the Herpes simplex antigen Lupidon H, resp. Lupidon G]. The results of treatment with LUPIDON achieved by 215 dermatologists with reference to a total number of 1059 cases are reported taking into account the controlled evaluation of questionnaires. Due to the considerable number of patients and physicians involved in this clinical investigation the presuppositions for objectiveness in respect of statistical evaluation were especially favourable. The results of treatment with LUPIDON--LUPIDON H and LUPIDON G proved to be of equal effectiveness--can be denoted as very positive because of the good or very good effects that could be observed in more than 80% of all the cases concerned. Such a therapeutically favourable result refers primarily to Herpes labialis, Herpes genitalis and Herpes eruptions infesting trunk and head; other types of herpes disease, for example Herpes glutealis or stomatitis aphthosa were only improved to about 60%. The compatability of LUPIDON was striking. The rate of side-effects was at 3%. Moreover, other series of data are given with the intention to inform about criteria such as: Frequency of localisations with regard to Herpes simplex diseases; distribution according to sex of patients being suffering from Herpes labialis and Herpes genitalis; distribution according to age; duration of Herpes simplex before starting a treatment with LUPIDON; accompanying skin diseases."} {"id": "PMID:179235", "title": "[Moebius' syndrome and Poland's anomaly (author's transl)].", "content": "The syndrome of Moebius and Poland's anomaly have some features in common. The malformations of the limbs-especially those of the fingers (brady-, syn-, symbrachydactyly)-are identical in both disorders. Hypoplasia of the m. pectoralis major, characteristic for Poland's anomaly, may accompany Moebius' syndrome and cerebral nerve pareses may be associated with Poland's anomaly, thus distinction between the two disorders may be impossible. Both disorders affect the embryo at the same gestational age and the causative factor is unknown in either of them. Simultaneous evaluation of findings observed in patients suffering of either condition should be performed to elucidate pathogenesis and aetiology.", "contents": "[Moebius' syndrome and Poland's anomaly (author's transl)]. The syndrome of Moebius and Poland's anomaly have some features in common. The malformations of the limbs-especially those of the fingers (brady-, syn-, symbrachydactyly)-are identical in both disorders. Hypoplasia of the m. pectoralis major, characteristic for Poland's anomaly, may accompany Moebius' syndrome and cerebral nerve pareses may be associated with Poland's anomaly, thus distinction between the two disorders may be impossible. Both disorders affect the embryo at the same gestational age and the causative factor is unknown in either of them. Simultaneous evaluation of findings observed in patients suffering of either condition should be performed to elucidate pathogenesis and aetiology."} {"id": "PMID:179233", "title": "Spectrometric and biological data of 1, N6-ethenoadenosine 3', 5'-cyclic monophosphate.", "content": "Spectroscopic properties of 1, N6-ethenoadenosine cyclic 3', 5'-monophosphate were studied and compared with cyclic adenosine 3', 5'-monophosphate. Date of nuclear magnetic resonance-, mass-, ultraviolet-, and fluorescence spectroscopy were given. Additionally biochemical activity was tested in protein kinase system of beef adrenals. No significant biological difference between cyclic adenosine 3', 5'-monophosphate and its fluorescent analog has been found.", "contents": "Spectrometric and biological data of 1, N6-ethenoadenosine 3', 5'-cyclic monophosphate. Spectroscopic properties of 1, N6-ethenoadenosine cyclic 3', 5'-monophosphate were studied and compared with cyclic adenosine 3', 5'-monophosphate. Date of nuclear magnetic resonance-, mass-, ultraviolet-, and fluorescence spectroscopy were given. Additionally biochemical activity was tested in protein kinase system of beef adrenals. No significant biological difference between cyclic adenosine 3', 5'-monophosphate and its fluorescent analog has been found."} {"id": "PMID:179234", "title": "Mixed monomolecular films of chlorophyll and cytochromes.", "content": "Mixed monomolecular films of cytochrome (Cyt) and chlorophyll (Chl) were spread at a nitrogen-water interface. A large interaction is observed between reduced Cyt f and Chl a in a mixed film. Oxidized Cyt f and Chl a in a mixed film show little evidence for interaction. Mixed monomolecular films of Chl a with either reduced or oxidized Cyt c appears to result in denaturation of the protein at the surface. A light reaction is observed only in mixed films of reduced Cy f and Chl a.", "contents": "Mixed monomolecular films of chlorophyll and cytochromes. Mixed monomolecular films of cytochrome (Cyt) and chlorophyll (Chl) were spread at a nitrogen-water interface. A large interaction is observed between reduced Cyt f and Chl a in a mixed film. Oxidized Cyt f and Chl a in a mixed film show little evidence for interaction. Mixed monomolecular films of Chl a with either reduced or oxidized Cyt c appears to result in denaturation of the protein at the surface. A light reaction is observed only in mixed films of reduced Cy f and Chl a."} {"id": "PMID:179249", "title": "[On the determination of coffeine in soft drinks and coffeine-containing food preparations (author's transl)].", "content": "The recently proposed spectroscopical determination of coffeine in soft drinks after filtration of polyamide leads to higher coffeine values than originally present, due to substances absorbed by the UV light. Therefore a method is proposed for identification and quantitative determination of coffeine in soft drinks and in methanol extracts of coffeine-containing foods by column chromatography on silical gel.", "contents": "[On the determination of coffeine in soft drinks and coffeine-containing food preparations (author's transl)]. The recently proposed spectroscopical determination of coffeine in soft drinks after filtration of polyamide leads to higher coffeine values than originally present, due to substances absorbed by the UV light. Therefore a method is proposed for identification and quantitative determination of coffeine in soft drinks and in methanol extracts of coffeine-containing foods by column chromatography on silical gel."} {"id": "PMID:179250", "title": "[Light and electron microscopie examination of a case of primary liver carcinoma in an infant (author's transl)].", "content": "The course of an infantial liver carcinoma is reported. Two liver biopsies and autopsy material were studied by light- and electron microscope. The histological findings and the clinical data are discussed. The first biopsy taken from the liver showed glycogen storage within the hepatic cells. It is suggested that this phenomenon is consistent with the preblastomatous stage of the liver cells. This fact is supported also by experimental way. The detection of this glycogen storage could be used as an early sign of the liver cancer in childhood, and might stress an early surgical intervention.", "contents": "[Light and electron microscopie examination of a case of primary liver carcinoma in an infant (author's transl)]. The course of an infantial liver carcinoma is reported. Two liver biopsies and autopsy material were studied by light- and electron microscope. The histological findings and the clinical data are discussed. The first biopsy taken from the liver showed glycogen storage within the hepatic cells. It is suggested that this phenomenon is consistent with the preblastomatous stage of the liver cells. This fact is supported also by experimental way. The detection of this glycogen storage could be used as an early sign of the liver cancer in childhood, and might stress an early surgical intervention."} {"id": "PMID:179251", "title": "[Medical evaluation and rehabilitation following intensive therapy of malignomas in the female genitalia and breast].", "content": "The selective therapy of malignant tumours of the female genital tract has led to the abandonment of radical procedures in the treatment of early stages of carcinomas. The histological diagnosis, including tumour localisation, tumour grading, applied therapy, early and late complications are criterion to be taken into consideration in laying down the degree of infirmity. In the light of functional gynaecology, principles for such patients care are laid down, taking into account the time of disablement as well as problems of rehabilitation, not only for patients with malignant tumours of the female genitals but for those with mammary tumours as well.", "contents": "[Medical evaluation and rehabilitation following intensive therapy of malignomas in the female genitalia and breast]. The selective therapy of malignant tumours of the female genital tract has led to the abandonment of radical procedures in the treatment of early stages of carcinomas. The histological diagnosis, including tumour localisation, tumour grading, applied therapy, early and late complications are criterion to be taken into consideration in laying down the degree of infirmity. In the light of functional gynaecology, principles for such patients care are laid down, taking into account the time of disablement as well as problems of rehabilitation, not only for patients with malignant tumours of the female genitals but for those with mammary tumours as well."} {"id": "PMID:179252", "title": "[Effects of estrogenic hormones on blood lipids].", "content": "The authors have followed the effects of application of the deposit estradiolbenzoat on the blood lipides level of women at the beginning of menopause and women with arteriosclerosis. They have registered a moderate drop of the concentration of cholesterol, beta-lipoproteins, and slight changes of the non-esterified fatty acids level. Women using contraceptive hormonal mixtures were found with higher level of cholesterol in the blood serum than those being watched. The application of a single dose of androgen did not have any substantial effects on the blood lipides level.", "contents": "[Effects of estrogenic hormones on blood lipids]. The authors have followed the effects of application of the deposit estradiolbenzoat on the blood lipides level of women at the beginning of menopause and women with arteriosclerosis. They have registered a moderate drop of the concentration of cholesterol, beta-lipoproteins, and slight changes of the non-esterified fatty acids level. Women using contraceptive hormonal mixtures were found with higher level of cholesterol in the blood serum than those being watched. The application of a single dose of androgen did not have any substantial effects on the blood lipides level."} {"id": "PMID:179253", "title": "[In vitro studies of the antiviral activity of enzymatically oxidized o-diphenolic compounds against herpes simplex virus type 1 and 2 (author's transl)].", "content": "Oxidation of the o-diphenolic compounds, catechol, protocatechuic acid, caffeic acid, and chlorogenic acid by o-diphenol oxidase (EC 1.10.3.1) resulted in compounds with antiviral activity against herpes simplex virus types 1 and 2. In the system HSV-1/rabbit kidney primary cells, a 90 per cent plaque reduction was obtained by the oxidation product from 1 mug caffeic acid, 9 mug catechol, 13 mug chlorogenic acid, or 20 mug protocatechuic acid (per ml), respectively. In comparision to the basic compounds or those oxidized in the presence of bovine serum albumin, the inhibitory effect of oxidized o-diphenolic compounds free from albumin was higher. From the basic o-diphenolic compounds, only catechol and caffeic acid showed remarkable antiviral activities in the system investigated. Although there have not experiments on the mechanism of action yet been the compounds are supposed to act during the earliest phases of the HSV-multiplication, because o-diphenolic compounds had been found to be present in the virus-cell system only 90 minutes after infection. In this respect the substances were similar to those of humic acids which also inhibit the adsorption phase of herpes simplex virus. There were no essential differences between herpes simplex virus type 1 and type 2 in respect of their sensitivity to enzymatically oxidized o-diphenolic compounds.", "contents": "[In vitro studies of the antiviral activity of enzymatically oxidized o-diphenolic compounds against herpes simplex virus type 1 and 2 (author's transl)]. Oxidation of the o-diphenolic compounds, catechol, protocatechuic acid, caffeic acid, and chlorogenic acid by o-diphenol oxidase (EC 1.10.3.1) resulted in compounds with antiviral activity against herpes simplex virus types 1 and 2. In the system HSV-1/rabbit kidney primary cells, a 90 per cent plaque reduction was obtained by the oxidation product from 1 mug caffeic acid, 9 mug catechol, 13 mug chlorogenic acid, or 20 mug protocatechuic acid (per ml), respectively. In comparision to the basic compounds or those oxidized in the presence of bovine serum albumin, the inhibitory effect of oxidized o-diphenolic compounds free from albumin was higher. From the basic o-diphenolic compounds, only catechol and caffeic acid showed remarkable antiviral activities in the system investigated. Although there have not experiments on the mechanism of action yet been the compounds are supposed to act during the earliest phases of the HSV-multiplication, because o-diphenolic compounds had been found to be present in the virus-cell system only 90 minutes after infection. In this respect the substances were similar to those of humic acids which also inhibit the adsorption phase of herpes simplex virus. There were no essential differences between herpes simplex virus type 1 and type 2 in respect of their sensitivity to enzymatically oxidized o-diphenolic compounds."} {"id": "PMID:179254", "title": "[About the influence of beta-toxin of Clostridium perfringens (type C) on the motorics of intestine segments (in vitro). I. Communication].", "content": "The Beta-Toxin of Clostridium perfringens (Type C) was introduced intra lumen to jejunum and ileum segments of rabbits, then examined by pharmacologic method (in vitro). The Beta-Toxin showed a paralysing activity on the motorics of the intestine which fact may be in relation to the paralysing activity of this toxin in dysenteria in piglets.", "contents": "[About the influence of beta-toxin of Clostridium perfringens (type C) on the motorics of intestine segments (in vitro). I. Communication]. The Beta-Toxin of Clostridium perfringens (Type C) was introduced intra lumen to jejunum and ileum segments of rabbits, then examined by pharmacologic method (in vitro). The Beta-Toxin showed a paralysing activity on the motorics of the intestine which fact may be in relation to the paralysing activity of this toxin in dysenteria in piglets."} {"id": "PMID:179256", "title": "Drug controlled of Cushing's syndrome. Combined aminoglutethimide and metyrapone therapy.", "content": "Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.", "contents": "Drug controlled of Cushing's syndrome. Combined aminoglutethimide and metyrapone therapy. Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases."} {"id": "PMID:179257", "title": "Evidence for the adrenal source of androgens in precocious adrenarche.", "content": "In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum delta4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals. Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin or Ovral produced variable changes. These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition.", "contents": "Evidence for the adrenal source of androgens in precocious adrenarche. In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum delta4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals. Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin or Ovral produced variable changes. These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition."} {"id": "PMID:179258", "title": "Ovarian biochemical competence following gonadotrophic deprivation from birth.", "content": "Normal ovarian morphogenesis is impaired by the absence of gonadotrophic hormones from birth. In the present study, the following question was asked: Does gonadotrophic deprivation also affect ovarian biochemical competence? Newborn mice were treated daily with an antiserum neutralizing endogenous circulating gonadotrophins. At the age of 14 days, ovaries from these mice and control littermates were incubated in the presence and absence of gonadotrophic preparations; cAMP and lactic acid levels were then measured in tissue and incubation medium. Ovaries from anti-gonadotrophin treated and control mice had the same basal levels, per mg tissue, of cAMP and lactic acid. Moreover, the levels increased to approximately the same extent following in vitro gonadotrophic stimulation: an increase in cAMP of 8-10-fold (using a preparation with an hLH:hFSH ratio of 1:1) or 2 1/2-fold (using a preparation with an hLH:hFSH ratio of 1:5), and about a 2-fold increase in lactic acid (using oLH). The acute effect of gonadotrophins on ovarian glycolysis, reported up till now only in the rat ovary, is the first such demonstration in mice. The results also indicate that despite impaired morphogenesis, the enzymatic systems necessary for ovarian glycolysis (as measured by lactic acid production) and cAMP formation can develop without gonadotrophic participation. Furthermore, ovarian capacity to respond to hormonal stimulation is acquired post-natally, as shown by refractoriness to gonadotrophic stimulation during the first week of life. Finally, post-natal gonadotrophic exposure does not seem an essential requirement, at least as measured by the above parameters, for acquiring ovarian competence to respond to hormonal stimulation.", "contents": "Ovarian biochemical competence following gonadotrophic deprivation from birth. Normal ovarian morphogenesis is impaired by the absence of gonadotrophic hormones from birth. In the present study, the following question was asked: Does gonadotrophic deprivation also affect ovarian biochemical competence? Newborn mice were treated daily with an antiserum neutralizing endogenous circulating gonadotrophins. At the age of 14 days, ovaries from these mice and control littermates were incubated in the presence and absence of gonadotrophic preparations; cAMP and lactic acid levels were then measured in tissue and incubation medium. Ovaries from anti-gonadotrophin treated and control mice had the same basal levels, per mg tissue, of cAMP and lactic acid. Moreover, the levels increased to approximately the same extent following in vitro gonadotrophic stimulation: an increase in cAMP of 8-10-fold (using a preparation with an hLH:hFSH ratio of 1:1) or 2 1/2-fold (using a preparation with an hLH:hFSH ratio of 1:5), and about a 2-fold increase in lactic acid (using oLH). The acute effect of gonadotrophins on ovarian glycolysis, reported up till now only in the rat ovary, is the first such demonstration in mice. The results also indicate that despite impaired morphogenesis, the enzymatic systems necessary for ovarian glycolysis (as measured by lactic acid production) and cAMP formation can develop without gonadotrophic participation. Furthermore, ovarian capacity to respond to hormonal stimulation is acquired post-natally, as shown by refractoriness to gonadotrophic stimulation during the first week of life. Finally, post-natal gonadotrophic exposure does not seem an essential requirement, at least as measured by the above parameters, for acquiring ovarian competence to respond to hormonal stimulation."} {"id": "PMID:179255", "title": "Herpesvirus in bladder cancer.", "content": "A case of squamous cell carcinoma of the urinary bladder in which herpesvirus virions could be identified by electron microscopy is presented. The value of cytology in the recognition of the typical intranuclear inclusions which led to the initiation of further studies is emphasized. Recent evidence concerning the relationship between herpesviruses and human cancer is briefly reviewed. Although previous reports have emphasized the association of HSV and uterine cervical carcinoma, other combinations, especially with neoplasms of squamous cell type, have been reported. The accumulation of additional cases in which viruses can be demonstrated in cancers will help to define their role in human neoplasia.", "contents": "Herpesvirus in bladder cancer. A case of squamous cell carcinoma of the urinary bladder in which herpesvirus virions could be identified by electron microscopy is presented. The value of cytology in the recognition of the typical intranuclear inclusions which led to the initiation of further studies is emphasized. Recent evidence concerning the relationship between herpesviruses and human cancer is briefly reviewed. Although previous reports have emphasized the association of HSV and uterine cervical carcinoma, other combinations, especially with neoplasms of squamous cell type, have been reported. The accumulation of additional cases in which viruses can be demonstrated in cancers will help to define their role in human neoplasia."} {"id": "PMID:179259", "title": "The response of the immature rat ovary to gonadotrophins: acute changes in cyclic AMP, progesteron, testosteron, androstenedione and oestradiol after treatment with PMS or FSH + LH.", "content": "Radioimmunoassays were used to measure changes in progesterone, testosterone, androstenedione, oestradiol, gonadotrophin and ovarian cyclic AMP in immature female rats during the first 24 h after exposure to slowly (PMS) or rapidly (FSH + LH) disappearing gonadotrophins. Cyclic AMP was increased 30 min after injection of either kind of gonadotrophin but it had returned to control level within 4 h. Serum and ovarian testosterone and androstenedione also increased to a peak at 30 min but decreased to base line by the 4th h. Multiple injections of FSH + LH maintained an elevated serum testosterone level but they had little effect upon the secretion of androstenedione. Serum and ovarian progesterone increased quickly after treatment with gonadotrophin. With PMS the peak in the serum was reached at 8 h, it remained high for 4 h and then fell precipitously between the 12th and 16th h. FSH + LH produced a prompt increase in serum progesterone but the level could be maintained only by repeated doses given every 4 h. Oestradiol was not increased in the serum or the ovot produce an increase in oestrogen but a transient increase was found with 3 doses; 4 doses kept an elevated level of oestradiol for 12 h. These results indicate that the aromatizing system of the immature rat ovary is relatively inactive and that continual stimulation by gonadotrophin for about 10-12 h is necessary to bring about increased function. In contrast, the mechanisms for the synthesis and secretion of progesterone and androgens are vary active and can be immediately stimulated by exposure to gonadotrophins.", "contents": "The response of the immature rat ovary to gonadotrophins: acute changes in cyclic AMP, progesteron, testosteron, androstenedione and oestradiol after treatment with PMS or FSH + LH. Radioimmunoassays were used to measure changes in progesterone, testosterone, androstenedione, oestradiol, gonadotrophin and ovarian cyclic AMP in immature female rats during the first 24 h after exposure to slowly (PMS) or rapidly (FSH + LH) disappearing gonadotrophins. Cyclic AMP was increased 30 min after injection of either kind of gonadotrophin but it had returned to control level within 4 h. Serum and ovarian testosterone and androstenedione also increased to a peak at 30 min but decreased to base line by the 4th h. Multiple injections of FSH + LH maintained an elevated serum testosterone level but they had little effect upon the secretion of androstenedione. Serum and ovarian progesterone increased quickly after treatment with gonadotrophin. With PMS the peak in the serum was reached at 8 h, it remained high for 4 h and then fell precipitously between the 12th and 16th h. FSH + LH produced a prompt increase in serum progesterone but the level could be maintained only by repeated doses given every 4 h. Oestradiol was not increased in the serum or the ovot produce an increase in oestrogen but a transient increase was found with 3 doses; 4 doses kept an elevated level of oestradiol for 12 h. These results indicate that the aromatizing system of the immature rat ovary is relatively inactive and that continual stimulation by gonadotrophin for about 10-12 h is necessary to bring about increased function. In contrast, the mechanisms for the synthesis and secretion of progesterone and androgens are vary active and can be immediately stimulated by exposure to gonadotrophins."} {"id": "PMID:179260", "title": "Alpha 1-antitrypsin phenotypes in cirrhosis and hepatoma.", "content": "The phenotypic distribution of alpha-1-antitrypsin variants has been studied in 101 patients with cirrhosis and in 50 with cirrhosis plus hepatoma. 504 healthy Greeks served as controls. The ZZ and MZ phenotypes were found only once in the group of cirrhosis. The very low PiZ gene frequency suggests that the association of PiZ gene with cirrhosis is fortuitous. The FM phenotype has been observed in 14% of patients with hepatoma arised on cirrhosis and this incidence differed significantly between the two groups of patients and the controls. It is possible that cirrhotic patients phenotypically FM develop for as yet unknown reasons hepatoma in high percentage.", "contents": "Alpha 1-antitrypsin phenotypes in cirrhosis and hepatoma. The phenotypic distribution of alpha-1-antitrypsin variants has been studied in 101 patients with cirrhosis and in 50 with cirrhosis plus hepatoma. 504 healthy Greeks served as controls. The ZZ and MZ phenotypes were found only once in the group of cirrhosis. The very low PiZ gene frequency suggests that the association of PiZ gene with cirrhosis is fortuitous. The FM phenotype has been observed in 14% of patients with hepatoma arised on cirrhosis and this incidence differed significantly between the two groups of patients and the controls. It is possible that cirrhotic patients phenotypically FM develop for as yet unknown reasons hepatoma in high percentage."} {"id": "PMID:179261", "title": "[Histochemical and histological studies on the vagina of pigs with in various phases of the estrus cycle (author's transl)].", "content": "During estrus (1st day) the vaginal epithelium is highly proliferated; its thickness amounts up to 20 cell layers and even more. During metestrus (3rd day) the epithelium measures 12 to 15 layers due to degeneration and desquamation. During diestrus a further decrease in height is noticed. During late diestrus (16th day) the epithelium reaches its minimal height with 3 to 5 layers. The stratum superficiale consists during this phase of tall columnar cells. Starting from day 18 proliferation begins again. During all phases of the genital cycle the presence of infiltrated leucocytes is highest during middle and late diestrus. Leucocytes are easily recognized by their strong reaction for alkaline phosphatase whereas the epithelium proper remains negative. Mucification in the porcine vaginal epithelium is but moderate. Mucous substances occupy from from proestrus to early diestrus the intercellular gaps in the adluminal half of the epithelium. During middle and late diestrus mucous substances are localized in the supranuclear region of the superficial columnar cells. Histochemical tests for enzymes of oxidative pathways give relatively uniform and weak results during the entire cycle. Fluctuations of epithelial esterase activity may be correlated with phases of proliferation and differentiation.", "contents": "[Histochemical and histological studies on the vagina of pigs with in various phases of the estrus cycle (author's transl)]. During estrus (1st day) the vaginal epithelium is highly proliferated; its thickness amounts up to 20 cell layers and even more. During metestrus (3rd day) the epithelium measures 12 to 15 layers due to degeneration and desquamation. During diestrus a further decrease in height is noticed. During late diestrus (16th day) the epithelium reaches its minimal height with 3 to 5 layers. The stratum superficiale consists during this phase of tall columnar cells. Starting from day 18 proliferation begins again. During all phases of the genital cycle the presence of infiltrated leucocytes is highest during middle and late diestrus. Leucocytes are easily recognized by their strong reaction for alkaline phosphatase whereas the epithelium proper remains negative. Mucification in the porcine vaginal epithelium is but moderate. Mucous substances occupy from from proestrus to early diestrus the intercellular gaps in the adluminal half of the epithelium. During middle and late diestrus mucous substances are localized in the supranuclear region of the superficial columnar cells. Histochemical tests for enzymes of oxidative pathways give relatively uniform and weak results during the entire cycle. Fluctuations of epithelial esterase activity may be correlated with phases of proliferation and differentiation."} {"id": "PMID:179262", "title": "[Effect of phenobarbital stimulation on morphological and cytoenzymatic changes in the liver of benzene intoxicated rats (author's transl)].", "content": "The experiments were carried out on male Wistar-Rats. They were divided into 2 groups. The rats of the control groups were treated to Phenobarbital intraperitoneally for 3 consecutive days. The animals of the experimental group were additionaly injected with Benzen intraperitoneally on the 4th day of experiment. It has been found that Phenobarbital brought about the formation of 2 types of bright and dark cells in the liver. The action of Phenobarbital is carried on by Benzene. The authors discuss morphological and functional evaluation of bright and dark cells from the point of view of stimulating action of Phenobarbital as well as the course of Benzene biotransformation in liver cells.", "contents": "[Effect of phenobarbital stimulation on morphological and cytoenzymatic changes in the liver of benzene intoxicated rats (author's transl)]. The experiments were carried out on male Wistar-Rats. They were divided into 2 groups. The rats of the control groups were treated to Phenobarbital intraperitoneally for 3 consecutive days. The animals of the experimental group were additionaly injected with Benzen intraperitoneally on the 4th day of experiment. It has been found that Phenobarbital brought about the formation of 2 types of bright and dark cells in the liver. The action of Phenobarbital is carried on by Benzene. The authors discuss morphological and functional evaluation of bright and dark cells from the point of view of stimulating action of Phenobarbital as well as the course of Benzene biotransformation in liver cells."} {"id": "PMID:179263", "title": "Parkinson's disease: distribution of Lewy bodies and monoamine neuron system.", "content": "A systematic study of the central and peripheral nervous systems in 3 cases of Parkinson's disease has demonstrated that Lewy bodies are present in 27 nuclei. Of these 20 nuclei (12 pigmented and 8 unpigmented) are involved in 2 or all 3 cases. It is noticed that the distribution of Lewy bodies in Parkinson's disease described here corresponds surprisingly well to that of monoamine (dopamine, noradrenaline and serotonin) cell bodies demonstrated in rats by the histochemical fluorescence method. This correlation is similar to that of Alzheimer's neurofibillary changes in postencephalitic Parkinsonism as described by Ishii. Inasmuch as these viewpoints are also in agreement with preciously reported biochemical data on Parkinsonism, it is suggested that Parkinsonism (idiopathic and postencephalitic) should represent a system degeneration of monoamine neuron systems.", "contents": "Parkinson's disease: distribution of Lewy bodies and monoamine neuron system. A systematic study of the central and peripheral nervous systems in 3 cases of Parkinson's disease has demonstrated that Lewy bodies are present in 27 nuclei. Of these 20 nuclei (12 pigmented and 8 unpigmented) are involved in 2 or all 3 cases. It is noticed that the distribution of Lewy bodies in Parkinson's disease described here corresponds surprisingly well to that of monoamine (dopamine, noradrenaline and serotonin) cell bodies demonstrated in rats by the histochemical fluorescence method. This correlation is similar to that of Alzheimer's neurofibillary changes in postencephalitic Parkinsonism as described by Ishii. Inasmuch as these viewpoints are also in agreement with preciously reported biochemical data on Parkinsonism, it is suggested that Parkinsonism (idiopathic and postencephalitic) should represent a system degeneration of monoamine neuron systems."} {"id": "PMID:179264", "title": "Retinal lipidosis in albino rats treated with chlorphentermine and with tricyclic antidepressants.", "content": "Retinal pigment epithelium is known to be engaged in continuous phagocytosis and digestion of old discs of visual cell outer segments, which have a high phospholipid content. The present ultrastructural study was focused mainly on the effects, upon pigment epithelium, of several drugs that are thought to interfere with the enzymatic degradation of phospholipids. Albino rats received high oral doses of chlorphentermine, iprindole, 1-chloroamitriptyline, imipramine, or clomipramine. After treatment for several weeks the pigment epithelial cells were doubled in height due to deposition of excessive amounts of abnormal cytoplasmic inclusions which had a crystalloid substructure. Such inclusions which are known from previous studies to be associated with drug-induced phospholipid storage are suggested to contain nondigestible phospholipids, which in pigment epithelium originate mainly from phagocytosed outer segment discs. The alterations were reversible by withdrawal of the drugs. The functional implications of the epithelial alterations remain to be elucidated. Additional examination of the neuroretina revealed numerous abnormal inclusions, mainly of multilamellated structure. Ganglion cells were affected most. The neuroretinal alterations were reminiscent of those described in human cases of inherited lipidoses.", "contents": "Retinal lipidosis in albino rats treated with chlorphentermine and with tricyclic antidepressants. Retinal pigment epithelium is known to be engaged in continuous phagocytosis and digestion of old discs of visual cell outer segments, which have a high phospholipid content. The present ultrastructural study was focused mainly on the effects, upon pigment epithelium, of several drugs that are thought to interfere with the enzymatic degradation of phospholipids. Albino rats received high oral doses of chlorphentermine, iprindole, 1-chloroamitriptyline, imipramine, or clomipramine. After treatment for several weeks the pigment epithelial cells were doubled in height due to deposition of excessive amounts of abnormal cytoplasmic inclusions which had a crystalloid substructure. Such inclusions which are known from previous studies to be associated with drug-induced phospholipid storage are suggested to contain nondigestible phospholipids, which in pigment epithelium originate mainly from phagocytosed outer segment discs. The alterations were reversible by withdrawal of the drugs. The functional implications of the epithelial alterations remain to be elucidated. Additional examination of the neuroretina revealed numerous abnormal inclusions, mainly of multilamellated structure. Ganglion cells were affected most. The neuroretinal alterations were reminiscent of those described in human cases of inherited lipidoses."} {"id": "PMID:179265", "title": "Inclusion bodies in brain cell cultures from Creutzfeldt-Jakob disease.", "content": "Brain cell cultures were established from 20 patients with various forms of dementia and studied for evidence of virus induced alterations. Changes were detected in the cultured cells from 1 patient (L.C.) with the clinical and pathological diagnosis of Creutzfeldt-Jakob disease. These changes were present in the early passages of the brain tissue and were not seen in the cultures from the other cases.", "contents": "Inclusion bodies in brain cell cultures from Creutzfeldt-Jakob disease. Brain cell cultures were established from 20 patients with various forms of dementia and studied for evidence of virus induced alterations. Changes were detected in the cultured cells from 1 patient (L.C.) with the clinical and pathological diagnosis of Creutzfeldt-Jakob disease. These changes were present in the early passages of the brain tissue and were not seen in the cultures from the other cases."} {"id": "PMID:179266", "title": "Primary angle-closure glaucoma. Oculometry, epidemiology, and genetics in a high risk population.", "content": "The ocular dimensions in patients suffering from primary angle-closure glaucoma (a.c.g.) have been studied in several clinical series, chiefly in Caucasians. The epidemiology and aetiology of a.c.g. are less well known although genetic factors seem to be involved. Eskimos have recently been shown to constitute a high risk population with respect to a.c.g. Consequently, a series of oculometric, epidemiologic, and genetic studies among Greenland Eskimos was undertaken. Besides the immediate purpose, prevention of blindness in this population, the survey had important general aspects and the following main results were obtained: 1a) Ocular dimensions, as well as clinical symptoms, in Eskimo a.c.g. patients correspond closely to those of a.c.g. reports from other ethnic groups and 1b) ocular dimensions of the anterior segment in the general Eskimo population deviate conspicuously towards the low level characteristic of all samples of a.c.g. patients. 2) A.c.g. prevalence rates were estimated at 1.6% in males and 5.1% in females of the general population aged 40 years or more. The epidemiology of a.c.g. seems to reflect closely the variations of axial anterior chamber depth (ACD) according to race (Eskimo, Caucasian), sex and age. Empirical a.c.g. risk estimates, depending on the ACD value, were obtained in elderly females. 3) A relatively shallow chamber was found in 1st and 2nd degree relatives of a.c.g. patients, in close agreement with an earlier study in Caucasians (T\u00f6rnquist 1953). However, also in the general Eskimo population a pronounced familial resemblance with respect to ACD and corneal diameter was found. Thus the family studies indicate that the size of the anterior chamber shows a mainly genetic determination, which probably constitutes the genetic basis of a.c.g. as well. With this background a hypothesis is discussed, which interprets the small anterior chambers in Eskimos as a result of genetic adaptation to arctic environment. Corneal protection may have been the significant advantage and the a.c.g. load in elderly persons a relatively less important cost.", "contents": "Primary angle-closure glaucoma. Oculometry, epidemiology, and genetics in a high risk population. The ocular dimensions in patients suffering from primary angle-closure glaucoma (a.c.g.) have been studied in several clinical series, chiefly in Caucasians. The epidemiology and aetiology of a.c.g. are less well known although genetic factors seem to be involved. Eskimos have recently been shown to constitute a high risk population with respect to a.c.g. Consequently, a series of oculometric, epidemiologic, and genetic studies among Greenland Eskimos was undertaken. Besides the immediate purpose, prevention of blindness in this population, the survey had important general aspects and the following main results were obtained: 1a) Ocular dimensions, as well as clinical symptoms, in Eskimo a.c.g. patients correspond closely to those of a.c.g. reports from other ethnic groups and 1b) ocular dimensions of the anterior segment in the general Eskimo population deviate conspicuously towards the low level characteristic of all samples of a.c.g. patients. 2) A.c.g. prevalence rates were estimated at 1.6% in males and 5.1% in females of the general population aged 40 years or more. The epidemiology of a.c.g. seems to reflect closely the variations of axial anterior chamber depth (ACD) according to race (Eskimo, Caucasian), sex and age. Empirical a.c.g. risk estimates, depending on the ACD value, were obtained in elderly females. 3) A relatively shallow chamber was found in 1st and 2nd degree relatives of a.c.g. patients, in close agreement with an earlier study in Caucasians (T\u00f6rnquist 1953). However, also in the general Eskimo population a pronounced familial resemblance with respect to ACD and corneal diameter was found. Thus the family studies indicate that the size of the anterior chamber shows a mainly genetic determination, which probably constitutes the genetic basis of a.c.g. as well. With this background a hypothesis is discussed, which interprets the small anterior chambers in Eskimos as a result of genetic adaptation to arctic environment. Corneal protection may have been the significant advantage and the a.c.g. load in elderly persons a relatively less important cost."} {"id": "PMID:179267", "title": "Synovial sarcoma: a case report.", "content": "The case described, of a 40-year-old woman with a 26-year history of a chronic, non-specific knee disorder, is a rather typical example of synovial sarcoma, according to the information given by other authors over the past three to four decades. The diagnostic difficulties and failures are clearly illustrated. It must be emphasized that severe, obscure joint symptoms such as our patient presented over the many years before death should have led to a proper surgical exploration of the knee. Furthermore, it should be unnecessary to stress the importance of performing a histological examination whenever excising abnormal tissue.", "contents": "Synovial sarcoma: a case report. The case described, of a 40-year-old woman with a 26-year history of a chronic, non-specific knee disorder, is a rather typical example of synovial sarcoma, according to the information given by other authors over the past three to four decades. The diagnostic difficulties and failures are clearly illustrated. It must be emphasized that severe, obscure joint symptoms such as our patient presented over the many years before death should have led to a proper surgical exploration of the knee. Furthermore, it should be unnecessary to stress the importance of performing a histological examination whenever excising abnormal tissue."} {"id": "PMID:179269", "title": "Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia.", "content": "A deficiency of extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase has been demonstrated in a boy with severe, persistent neonatal hypoglycaemia. Hepatic glucose-6-phosphatase, fructose-1.6-diphosphatase and pyruvate carboxylase were normal. The total activity of phosphoenolpyruvate carboxykinase was also normal, but the enzyme showed an abnormal subcellular distribution, virtually no activity being detected in the extramitochondrial fraction of a liver homogenate. The boy died at the age of 2 years 10 months. Autopsy revealed severe cerebral atrophy, atrophy of the optic nerve, and fatty infiltration of liver and kidney.", "contents": "Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia. A deficiency of extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase has been demonstrated in a boy with severe, persistent neonatal hypoglycaemia. Hepatic glucose-6-phosphatase, fructose-1.6-diphosphatase and pyruvate carboxylase were normal. The total activity of phosphoenolpyruvate carboxykinase was also normal, but the enzyme showed an abnormal subcellular distribution, virtually no activity being detected in the extramitochondrial fraction of a liver homogenate. The boy died at the age of 2 years 10 months. Autopsy revealed severe cerebral atrophy, atrophy of the optic nerve, and fatty infiltration of liver and kidney."} {"id": "PMID:179270", "title": "GH, ACTH, LH and FSH behaviour in the first seven days of life.", "content": "--43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2 +/- 34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p less than 0.01). Minimum level was reached on the 7th day. Plasma hCG-LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5 +/- 16.2 and 33.0 +/- 24.9 mU/ML, respectively). after this, plasma hCG-LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards.", "contents": "GH, ACTH, LH and FSH behaviour in the first seven days of life. --43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2 +/- 34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p less than 0.01). Minimum level was reached on the 7th day. Plasma hCG-LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5 +/- 16.2 and 33.0 +/- 24.9 mU/ML, respectively). after this, plasma hCG-LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards."} {"id": "PMID:179271", "title": "Neonatal hypertriglyceridemia: a new index of antepartum-intrapartum fetal stress?", "content": "The 95th percentile value of cord serum triglyceride concentration in 82 consecutively live born infants was found to be 0.79 mmol/l. This level was arbitrarily used to define neonatal hypertriglyceridemia. A comparison between 78 normotriglyceridemic and 61 hypertriglyceridemic newborn infants showed a significant association between elevated cord serum triglyceride concentration and insufficiency of the placenta, fetal bradycardia, meconium-stained amniotic fluid and one-minute Apgar score less than or equal to 7. A significantly (p less than 0.001) greater number of infants with one or several of these four factors, indicating antepartum and/or intrapartum fetal stress were found to be hypertriglyceridemic at birth. This finding suggests that estimation of cord serum triglyceride which is easy and inexpensive might be of value for a more complete evaluation of the newborn infant, and can serve as a supplement to the Apgar Score system.", "contents": "Neonatal hypertriglyceridemia: a new index of antepartum-intrapartum fetal stress? The 95th percentile value of cord serum triglyceride concentration in 82 consecutively live born infants was found to be 0.79 mmol/l. This level was arbitrarily used to define neonatal hypertriglyceridemia. A comparison between 78 normotriglyceridemic and 61 hypertriglyceridemic newborn infants showed a significant association between elevated cord serum triglyceride concentration and insufficiency of the placenta, fetal bradycardia, meconium-stained amniotic fluid and one-minute Apgar score less than or equal to 7. A significantly (p less than 0.001) greater number of infants with one or several of these four factors, indicating antepartum and/or intrapartum fetal stress were found to be hypertriglyceridemic at birth. This finding suggests that estimation of cord serum triglyceride which is easy and inexpensive might be of value for a more complete evaluation of the newborn infant, and can serve as a supplement to the Apgar Score system."} {"id": "PMID:179272", "title": "Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism.", "content": "A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.", "contents": "Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism. A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity."} {"id": "PMID:179268", "title": "Acute facial palsy. Some clinical and virological observations.", "content": "A prospective clinical and virological study on 44 patients with acute, peripheral facial paralysis was carried out in consecutive cases during one year. In 9 cases varicella-zoster infections were serologically established. In 5 additional patients an associated varicella-zoster, or herpes simplex, infection was possible. Of the 9 confirmed cases, 6 were clinically diagnosed as zoster oticus, whereas on clinical grounds, 3 were regarded as Bell's palsy. No evidence was obtained of associated enterovirus, mumps, measles, cytomegalovirus, tick-borne encephalitis virus, para-influenza virus, mononucleosis or Mycoplasma pneumoniae infection.", "contents": "Acute facial palsy. Some clinical and virological observations. A prospective clinical and virological study on 44 patients with acute, peripheral facial paralysis was carried out in consecutive cases during one year. In 9 cases varicella-zoster infections were serologically established. In 5 additional patients an associated varicella-zoster, or herpes simplex, infection was possible. Of the 9 confirmed cases, 6 were clinically diagnosed as zoster oticus, whereas on clinical grounds, 3 were regarded as Bell's palsy. No evidence was obtained of associated enterovirus, mumps, measles, cytomegalovirus, tick-borne encephalitis virus, para-influenza virus, mononucleosis or Mycoplasma pneumoniae infection."} {"id": "PMID:179273", "title": "Ceroid-like histiocytic granuloma of gall-bladder --a previously undescribed lesion--.", "content": "In the present study, 13 cases of a peculiar gall-bladder granuloma characterized by marked proliferation of ceroid-filled brown histiocytes were pathomorphologically, histochemically and ultrastructurally examined to define the pathologic features of such a lesion previously undescribed in the literature. The lesion grossly showed a granulomatous appearance of yellow brown to dark brown color developing in the wall of gall-bladder. Histologically, there was proliferation of histiocytes containing abundant brown pigment granules in their cytoplasm. The pigment granules proved to have staining characteristics closely resembling those of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic osmiophilic inclusions of heterogenous materials. With regard to the pathogenesis of this granuloma, it may be suggested that lipid components of bile juice, particularly unsaturated fatty acids and phospholipids, play an important role as a source of ceroidogenesis in the proliferating histiocytes.", "contents": "Ceroid-like histiocytic granuloma of gall-bladder --a previously undescribed lesion--. In the present study, 13 cases of a peculiar gall-bladder granuloma characterized by marked proliferation of ceroid-filled brown histiocytes were pathomorphologically, histochemically and ultrastructurally examined to define the pathologic features of such a lesion previously undescribed in the literature. The lesion grossly showed a granulomatous appearance of yellow brown to dark brown color developing in the wall of gall-bladder. Histologically, there was proliferation of histiocytes containing abundant brown pigment granules in their cytoplasm. The pigment granules proved to have staining characteristics closely resembling those of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic osmiophilic inclusions of heterogenous materials. With regard to the pathogenesis of this granuloma, it may be suggested that lipid components of bile juice, particularly unsaturated fatty acids and phospholipids, play an important role as a source of ceroidogenesis in the proliferating histiocytes."} {"id": "PMID:179274", "title": "An ultrastructural and histochemical study on bone lesions of Hand-Sch\u00fcller-Christian disease.", "content": "A correlated light microscopical, histochemical and ultrastructural study was made on bone lesions repeatedly biopsied from three patients with Hand-Sch\u00fcller-Christian disease. The histiocytic cells proliferating in the early lesions had a markedly indented nucleus and contained in their cytoplasm varying numbers of Langerhans cell granules and round or irregular-shaped lipid droplets. Histochemically, the lipid droplets were verified to the lipo-protein rich in fatty acids. Such histiocytic cells differ from highly phagocytic histiocytes or macrophages because of indistinct phagocytotic activity, and are regarded as a metabolic type of histiocytes. The late lesions were mostly dominated by a xanthogranulomatous tissue chiefly comprised of xanthoma cells and collagen fibers. The xanthoma cells were usually filled with numerous lipid vacuoles which were histochemically proved to mainly contain cholesterol. Almost all the xanthoma cells were closely attached to collagen fibers and often had well-developed rough endoplasmic reticula. Ultrastructurally, it is suggested that the xanthoma cells are originated from fibroblasts or fibrocytes. As an important factor to induce proliferation and xanthoma cell transformation of fibroblasts in the late phase, the presence of such a lipoprotein produced in the histiocytic cells of the early phase is emphasized.", "contents": "An ultrastructural and histochemical study on bone lesions of Hand-Sch\u00fcller-Christian disease. A correlated light microscopical, histochemical and ultrastructural study was made on bone lesions repeatedly biopsied from three patients with Hand-Sch\u00fcller-Christian disease. The histiocytic cells proliferating in the early lesions had a markedly indented nucleus and contained in their cytoplasm varying numbers of Langerhans cell granules and round or irregular-shaped lipid droplets. Histochemically, the lipid droplets were verified to the lipo-protein rich in fatty acids. Such histiocytic cells differ from highly phagocytic histiocytes or macrophages because of indistinct phagocytotic activity, and are regarded as a metabolic type of histiocytes. The late lesions were mostly dominated by a xanthogranulomatous tissue chiefly comprised of xanthoma cells and collagen fibers. The xanthoma cells were usually filled with numerous lipid vacuoles which were histochemically proved to mainly contain cholesterol. Almost all the xanthoma cells were closely attached to collagen fibers and often had well-developed rough endoplasmic reticula. Ultrastructurally, it is suggested that the xanthoma cells are originated from fibroblasts or fibrocytes. As an important factor to induce proliferation and xanthoma cell transformation of fibroblasts in the late phase, the presence of such a lipoprotein produced in the histiocytic cells of the early phase is emphasized."} {"id": "PMID:179276", "title": "Release of adenosine-like material from isolated perfused dog adipose tissue following sympathetic nerve stimulation and its inhibition by adrenergic alpha-receptor blockade.", "content": "Following the intraarterial infusion of 3H-adenine to isolated perfused canine subcutaneous adipose tissue, its adenine nucleotides are labelled. A continuous release of radioactivity, comprised of non-nucleotide material, was observed. The rate of this release was markedly enhanced by sympathetic nerve stimulation. The major components of the enhanced release appeared to be inosine and adenosine. Adrenergic alpha-receptor blockade (phentolamine or Hydergin) abolished the enhanced nucleoside release, while glycerol release was enhanced. The release of radioactivity was decreased during mechanical blood flow reduction and enhanced afterwards. However, the magnitude of this enhancement of release after clamp was much less than following nerve stimulation. The results suggest that adenosine or a closely related compound is released from canine subcutaneous adipose tissue by sympathetic nerve stimulation and that the release is related to adrenergic alpha-receptor stimulation. Since adenosine is a potent inhibitor of catecholamine induced lipolysis in this tissue the possibility of a regulatory role must be considered.", "contents": "Release of adenosine-like material from isolated perfused dog adipose tissue following sympathetic nerve stimulation and its inhibition by adrenergic alpha-receptor blockade. Following the intraarterial infusion of 3H-adenine to isolated perfused canine subcutaneous adipose tissue, its adenine nucleotides are labelled. A continuous release of radioactivity, comprised of non-nucleotide material, was observed. The rate of this release was markedly enhanced by sympathetic nerve stimulation. The major components of the enhanced release appeared to be inosine and adenosine. Adrenergic alpha-receptor blockade (phentolamine or Hydergin) abolished the enhanced nucleoside release, while glycerol release was enhanced. The release of radioactivity was decreased during mechanical blood flow reduction and enhanced afterwards. However, the magnitude of this enhancement of release after clamp was much less than following nerve stimulation. The results suggest that adenosine or a closely related compound is released from canine subcutaneous adipose tissue by sympathetic nerve stimulation and that the release is related to adrenergic alpha-receptor stimulation. Since adenosine is a potent inhibitor of catecholamine induced lipolysis in this tissue the possibility of a regulatory role must be considered."} {"id": "PMID:179277", "title": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. III. Effects from supraspinal pathways.", "content": "Supraspinal effects were investigated in interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as Ia inhibitory interneurones). It was revealed that volleys in the vestibulospinal tract may evoke mono- and disynaptic EPSPs in interneurones monosynaptically excited from extensor muscles, i.e. extensor coupled Ia inhibitory interneurones. Flexor coupled interneurones instead received disynaptic inhibition. Volleys in the rubrospinal tract evoked a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled interneurones. Disynaptic rubrospinal EPSPs and IPSPs were also revealed. The pyramidal tract also gives rise to a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled Ia inhibitory interneurones. Rubrospinal and pyramidal volleys were shown to facilitate transmission in various segmental reflex pathways to the Ia inhibitory interneurones. A detailed comparison reveals a striking parallelism of segmental and supraspinal effects on alpha-motoneurones and Ia inhibitory interneurones connected to the same muscles. This considerably strengthens the hypothesis of an \"alpha-gamma-linkage in the reciprocal inhibition\".", "contents": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. III. Effects from supraspinal pathways. Supraspinal effects were investigated in interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as Ia inhibitory interneurones). It was revealed that volleys in the vestibulospinal tract may evoke mono- and disynaptic EPSPs in interneurones monosynaptically excited from extensor muscles, i.e. extensor coupled Ia inhibitory interneurones. Flexor coupled interneurones instead received disynaptic inhibition. Volleys in the rubrospinal tract evoked a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled interneurones. Disynaptic rubrospinal EPSPs and IPSPs were also revealed. The pyramidal tract also gives rise to a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled Ia inhibitory interneurones. Rubrospinal and pyramidal volleys were shown to facilitate transmission in various segmental reflex pathways to the Ia inhibitory interneurones. A detailed comparison reveals a striking parallelism of segmental and supraspinal effects on alpha-motoneurones and Ia inhibitory interneurones connected to the same muscles. This considerably strengthens the hypothesis of an \"alpha-gamma-linkage in the reciprocal inhibition\"."} {"id": "PMID:179278", "title": "Effect of strength training on enzyme activities and fibre characteristics in human skeletal muscle.", "content": "Progressive strength training was performed 3 times a week for 8 weeks by 14 male students (19-31 yrs.). The training program consisted mainly of dynamic exercises for the leg extensors with maximal or close to maximal loads. The training caused significant improvements in dynamic and isometric strength. One repetition maximum in squats increased with 67%, Sargent jump with 22%, and maximal voluntary isometric contraction (MVC) with 13%, respectively. Body weight and leg muscle circumferences remained unchanged after training, whereas total body potassium, lean body mass and calculated total muscle mass increased, suggesting a change in body composition with training. Muscle biopsies were obtained from vastus lateralis for fibre analyses and determination of enzyme activities. There were no changes in muscle fibre composition or fibre area with training. The activities of Mg2+ stimulated ATPase, creatine phosphokinase and phosphofructokinase remained unchanged, whereas myokinase activity was increased after training from (1.41 to 1.52 moles x 10(-4) x g-1 x min-1, p less than 0.05). After training significant correlations (p less than 0.01) were demonstrated between Mg2+ stimulated ATPase activity and % fast twitch fibres (% FT) (r = 0.67), as well as between myokinase activity and % FT (r = 0.86).", "contents": "Effect of strength training on enzyme activities and fibre characteristics in human skeletal muscle. Progressive strength training was performed 3 times a week for 8 weeks by 14 male students (19-31 yrs.). The training program consisted mainly of dynamic exercises for the leg extensors with maximal or close to maximal loads. The training caused significant improvements in dynamic and isometric strength. One repetition maximum in squats increased with 67%, Sargent jump with 22%, and maximal voluntary isometric contraction (MVC) with 13%, respectively. Body weight and leg muscle circumferences remained unchanged after training, whereas total body potassium, lean body mass and calculated total muscle mass increased, suggesting a change in body composition with training. Muscle biopsies were obtained from vastus lateralis for fibre analyses and determination of enzyme activities. There were no changes in muscle fibre composition or fibre area with training. The activities of Mg2+ stimulated ATPase, creatine phosphokinase and phosphofructokinase remained unchanged, whereas myokinase activity was increased after training from (1.41 to 1.52 moles x 10(-4) x g-1 x min-1, p less than 0.05). After training significant correlations (p less than 0.01) were demonstrated between Mg2+ stimulated ATPase activity and % fast twitch fibres (% FT) (r = 0.67), as well as between myokinase activity and % FT (r = 0.86)."} {"id": "PMID:179279", "title": "Mitochondrial cytochrome concentrations in rat heart and liver as a consequence of different hypoxic periods.", "content": "Rat heart and liver cytochrome concentrations were determined after three hypoxic conditions (atmospheric pressure 50.5 kPa, 40.8 kPa and 38.0 kPa) lasting one week and two weeks. The heart showed clear hypertrophy which was 38% in most severe hypoxia (38 kPa, 2 weeks). A small decline in the liver weight to body weight ratio was observed, this decrease being 21% in the most severe case. During the hypoxic periods the mitochondrial cytochrome concentration decreased. This phenomenon was more obvious when the degree of hypoxia was increased and more pronounced after 2 weeks than one week. The heart and liver showed quite similar patterns in this respect. In most severe hypoxia the decreases in the liver were 29% for cytochrome aa3, 30% for cytochrome b, 20% for cytochrome c and 15% for cytochrome c1, with the concentrations expressed on mitochondrial protein basis. The corresponding values in the heart were 31%, 43%, 28%, and 22%. It can be concluded that in mammals the mitochondrial cytochrome content probably varies according to the amount of oxygen available.", "contents": "Mitochondrial cytochrome concentrations in rat heart and liver as a consequence of different hypoxic periods. Rat heart and liver cytochrome concentrations were determined after three hypoxic conditions (atmospheric pressure 50.5 kPa, 40.8 kPa and 38.0 kPa) lasting one week and two weeks. The heart showed clear hypertrophy which was 38% in most severe hypoxia (38 kPa, 2 weeks). A small decline in the liver weight to body weight ratio was observed, this decrease being 21% in the most severe case. During the hypoxic periods the mitochondrial cytochrome concentration decreased. This phenomenon was more obvious when the degree of hypoxia was increased and more pronounced after 2 weeks than one week. The heart and liver showed quite similar patterns in this respect. In most severe hypoxia the decreases in the liver were 29% for cytochrome aa3, 30% for cytochrome b, 20% for cytochrome c and 15% for cytochrome c1, with the concentrations expressed on mitochondrial protein basis. The corresponding values in the heart were 31%, 43%, 28%, and 22%. It can be concluded that in mammals the mitochondrial cytochrome content probably varies according to the amount of oxygen available."} {"id": "PMID:179280", "title": "Mechanical and metabolic effects of beta-receptor stimulators, the C-terminal octapeptide of cholecystokinin, and prostaglandin E2 on the isolated, depolarized sphincter of Oddi.", "content": "Similar to their actions on normally polarized, isolated sphincter of Oddi, the beta-receptor stimulators isoprenaline and tebutaline, and prostaglandin E2 produced relaxation of the depolarized preparation. The relaxation was accompained by an increase in the intracellular content of cyclic AMP. In contrast to its relaxing effect on normally polarized sphincter preparations, the C-terminal octapeptide of cholecystokinin (C8-CCK) contracted or had no effect on the depolarized sphincter. There was no change or a small decrease in the content of cyclic AMP in the muscle. It is suggested that the relaxing effects of beta-receptor stimulators and prostaglandin E2 on isolated sphinceter of Oddi, and the simultaneous increase in cyclic AMP-content are mediated processes independent of the electrical acitivty of the membrane. However, C8-CCK mediated relaxation and increase in cyclic AMP is dependent on the membrane potential.", "contents": "Mechanical and metabolic effects of beta-receptor stimulators, the C-terminal octapeptide of cholecystokinin, and prostaglandin E2 on the isolated, depolarized sphincter of Oddi. Similar to their actions on normally polarized, isolated sphincter of Oddi, the beta-receptor stimulators isoprenaline and tebutaline, and prostaglandin E2 produced relaxation of the depolarized preparation. The relaxation was accompained by an increase in the intracellular content of cyclic AMP. In contrast to its relaxing effect on normally polarized sphincter preparations, the C-terminal octapeptide of cholecystokinin (C8-CCK) contracted or had no effect on the depolarized sphincter. There was no change or a small decrease in the content of cyclic AMP in the muscle. It is suggested that the relaxing effects of beta-receptor stimulators and prostaglandin E2 on isolated sphinceter of Oddi, and the simultaneous increase in cyclic AMP-content are mediated processes independent of the electrical acitivty of the membrane. However, C8-CCK mediated relaxation and increase in cyclic AMP is dependent on the membrane potential."} {"id": "PMID:179282", "title": "Effects of emulsified iodo-lipids. A toxicologic investigation in the rabbit.", "content": "Two different iodized oil emulsion have been intravascularly injected into rabbits, one with a particle size of 15 mum or more and one with a size of about 1 mum. The effects of the emulsions have been evaluated on the brain, the heart, the kidney, the liver and the circulation. The reactions to the small particle emulsion was minor, especially if administered slowly. The injection site was of critical importance. The safest place for injection was the superior mesenteric artery. If supplied directly to the brain or the heart the emulsions were often deleterious, particularly the coarse one.", "contents": "Effects of emulsified iodo-lipids. A toxicologic investigation in the rabbit. Two different iodized oil emulsion have been intravascularly injected into rabbits, one with a particle size of 15 mum or more and one with a size of about 1 mum. The effects of the emulsions have been evaluated on the brain, the heart, the kidney, the liver and the circulation. The reactions to the small particle emulsion was minor, especially if administered slowly. The injection site was of critical importance. The safest place for injection was the superior mesenteric artery. If supplied directly to the brain or the heart the emulsions were often deleterious, particularly the coarse one."} {"id": "PMID:179283", "title": "Whole-body autoradiography of 99Tcm-labelled pyrophosphate and related compounds in young rats.", "content": "The distribution of 99Tcm-labelled pyrophosphate in young rats was analysed by wholebody autoradiography and compared with those observed for 99Tcm-pertechnetate, 32P-labelled pyrophosphate and 85Sr-chloride. 99Tcm-labelled pyrophosphate was rapidly accumulated in bone and dentine and was similar to 32P-labelled pyrophosphate and 85Sr-chloride. The uptake of these substances in developing enamel was rather low in contrast to 99Tcm-pertechnetate, which had no affinity for bone.", "contents": "Whole-body autoradiography of 99Tcm-labelled pyrophosphate and related compounds in young rats. The distribution of 99Tcm-labelled pyrophosphate in young rats was analysed by wholebody autoradiography and compared with those observed for 99Tcm-pertechnetate, 32P-labelled pyrophosphate and 85Sr-chloride. 99Tcm-labelled pyrophosphate was rapidly accumulated in bone and dentine and was similar to 32P-labelled pyrophosphate and 85Sr-chloride. The uptake of these substances in developing enamel was rather low in contrast to 99Tcm-pertechnetate, which had no affinity for bone."} {"id": "PMID:179284", "title": "Electron microscopy of Rous sarcoma virus genome RNA and its heat-dissociated subunits.", "content": "Native and heat-treated RNAs from the purified Schmidt-Ruppin strain of Rous sarcoma virus (RSV) were fractionated by sucrose density gradients in the presence of ribonuclease inhibitor diethyl-pyrocarbonate and observed by electron microscopy. The structure of native 60-70S RNA was classified into two forms: tanglefolded type and linear type. In the tangle-folded type double stranded portions were observed in several sites. A high frequency of 60-70S RNA were 1.0 mum and 3-3.5 mum in length. Molecules with length about 9mum were of the tangle-folded type while molecules shorter than 6 mum were of the linear form. The structure of heat-treated RNA(30-40S) was linear with the most frequent length being 1-1.5 mum. These results indicate that native 60-70S RNA is folded with the total molecular length being in the order of 6 to 9 mum. Molecules about 3mum long are likely to be the main subunits of 60-70S RNA, and they are fragmented further into smaller subunits of about 1 mum length.", "contents": "Electron microscopy of Rous sarcoma virus genome RNA and its heat-dissociated subunits. Native and heat-treated RNAs from the purified Schmidt-Ruppin strain of Rous sarcoma virus (RSV) were fractionated by sucrose density gradients in the presence of ribonuclease inhibitor diethyl-pyrocarbonate and observed by electron microscopy. The structure of native 60-70S RNA was classified into two forms: tanglefolded type and linear type. In the tangle-folded type double stranded portions were observed in several sites. A high frequency of 60-70S RNA were 1.0 mum and 3-3.5 mum in length. Molecules with length about 9mum were of the tangle-folded type while molecules shorter than 6 mum were of the linear form. The structure of heat-treated RNA(30-40S) was linear with the most frequent length being 1-1.5 mum. These results indicate that native 60-70S RNA is folded with the total molecular length being in the order of 6 to 9 mum. Molecules about 3mum long are likely to be the main subunits of 60-70S RNA, and they are fragmented further into smaller subunits of about 1 mum length."} {"id": "PMID:179285", "title": "Avian myeloblastosis virus-induced lymphosarcoma producing erythroblastic leucosis in chicks.", "content": "Acute myeloblastosis and several forms of tumor, including one case of lymphosarcoma occurred when avian myeloblastosis virus (BAI-A strain) was inoculated into newly hatched chicks (SPF). The homogenate of lymphosarcoma inoculated intraperitoneally into other newly hatched chicks induced a high incidence of erythroblastic leucosis. Electron microscopy did not reveal the presence of C-type virus particles in the tumor tissue. The relationship between avian myeloblastosis virus, lymphosarcoma and erythroblastic leucosis is discussed.", "contents": "Avian myeloblastosis virus-induced lymphosarcoma producing erythroblastic leucosis in chicks. Acute myeloblastosis and several forms of tumor, including one case of lymphosarcoma occurred when avian myeloblastosis virus (BAI-A strain) was inoculated into newly hatched chicks (SPF). The homogenate of lymphosarcoma inoculated intraperitoneally into other newly hatched chicks induced a high incidence of erythroblastic leucosis. Electron microscopy did not reveal the presence of C-type virus particles in the tumor tissue. The relationship between avian myeloblastosis virus, lymphosarcoma and erythroblastic leucosis is discussed."} {"id": "PMID:179286", "title": "The effect of antilipolytic agents on cyclic AMP, free fatty acid and total catecholamine concentrations in plasma.", "content": "Plasma concentrations of adenosine 3':5' cyclic monophosphate (cyclic AMP) and free fatty acids have been measured in 15 patients with acute myocardial infarction and in 6 dogs given infusions of isoprenaline. Plasma total catecholamines were also estimated in the patients. Inhibition of adipose tissue lipolysis with a nicotinic acid analogue did not decrease plasma cyclic AMP concentrations, either in the patients or when elevated in the dogs, thus suggesting that this tissue is not a major source of the nucleotide in plasma.", "contents": "The effect of antilipolytic agents on cyclic AMP, free fatty acid and total catecholamine concentrations in plasma. Plasma concentrations of adenosine 3':5' cyclic monophosphate (cyclic AMP) and free fatty acids have been measured in 15 patients with acute myocardial infarction and in 6 dogs given infusions of isoprenaline. Plasma total catecholamines were also estimated in the patients. Inhibition of adipose tissue lipolysis with a nicotinic acid analogue did not decrease plasma cyclic AMP concentrations, either in the patients or when elevated in the dogs, thus suggesting that this tissue is not a major source of the nucleotide in plasma."} {"id": "PMID:179287", "title": "Production of 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-14beta-ol-17-ones and 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-17alpha-ol-14-ones by microbial enzymes.", "content": "For the purpose of producing hydroxy-keto-seco-steroids in which hydroxyl group is attached to a carbon atom having the R-configuration, numerous biochemically active microorganisms were tested without any success. The hydroxysteroid oxidoreductase enzymes of the investigated bacterial, yeast and fungal strains were suitable only for the production of 17beta-ol-14-one and 14alpha-ol-17-one derivatives. The required compounds were prepared by combinations of enzymatic reactions with chemical reduction. (i) By hydroxysteroid oxidoreductase of Saccharomyces uvarum and Saccharomyces drosophilarum, 17beta-ol-14-one and 14alpha-ol-17-one derivatives of 14,17-dione, respectively, were obtained. (ii) The above compounds were acetylated then reduced by sodium borohydride. (iii) 14beta,17beta-diol-17-acetate and 14alpha,17alpha-diol-14-acetate were dehydrogenated by dehydroxysteroid oxidoreductase of Nocardia sp. and Mycobacterum sp., respectively, in the presence of steroid esterase. The reaction mixture contained either 14beta-ol-17-one or 17alpha-ol-14-one derivatives, since oxidation by hydroxysteroid oxidoreductase was limited to the hydroxyl group attached to a carbon atom having the S-configuration.", "contents": "Production of 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-14beta-ol-17-ones and 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-17alpha-ol-14-ones by microbial enzymes. For the purpose of producing hydroxy-keto-seco-steroids in which hydroxyl group is attached to a carbon atom having the R-configuration, numerous biochemically active microorganisms were tested without any success. The hydroxysteroid oxidoreductase enzymes of the investigated bacterial, yeast and fungal strains were suitable only for the production of 17beta-ol-14-one and 14alpha-ol-17-one derivatives. The required compounds were prepared by combinations of enzymatic reactions with chemical reduction. (i) By hydroxysteroid oxidoreductase of Saccharomyces uvarum and Saccharomyces drosophilarum, 17beta-ol-14-one and 14alpha-ol-17-one derivatives of 14,17-dione, respectively, were obtained. (ii) The above compounds were acetylated then reduced by sodium borohydride. (iii) 14beta,17beta-diol-17-acetate and 14alpha,17alpha-diol-14-acetate were dehydrogenated by dehydroxysteroid oxidoreductase of Nocardia sp. and Mycobacterum sp., respectively, in the presence of steroid esterase. The reaction mixture contained either 14beta-ol-17-one or 17alpha-ol-14-one derivatives, since oxidation by hydroxysteroid oxidoreductase was limited to the hydroxyl group attached to a carbon atom having the S-configuration."} {"id": "PMID:179288", "title": "17Beta-hydroxysteroid dehydrogenase activity in Streptomyces hydrogenans.", "content": "Streptomyces hydrogenans converts 17beta-hydroxyandrost-4-ene-3-one (testosterone) to androst-4-ene-3,17-dione (androstenedione) in good yields. Time-dependence of the conversion, steroid uptake and release have been studied in vivo. Steroid analysis was done by thin-layer chromatography and recrystallization to constant specific radioactivity. After sonification of the cells the postulated 17beta-hydroxysteroid dehydrogenase activity was recovered in the 105 000 g supernatant. The enzyme was enriched by gel filtration on Sephadex G-200. It required NAD+ as cofactor. Its activity could be studied photometrically, because there are no further testosterone-netabolites. If S. hydrogenans was cultured in the presence of testosterone, estradiol or 5alphaH-dihydrotestosterone, the activity of 17beta-hydroxysteroid dehydrogenase increased.", "contents": "17Beta-hydroxysteroid dehydrogenase activity in Streptomyces hydrogenans. Streptomyces hydrogenans converts 17beta-hydroxyandrost-4-ene-3-one (testosterone) to androst-4-ene-3,17-dione (androstenedione) in good yields. Time-dependence of the conversion, steroid uptake and release have been studied in vivo. Steroid analysis was done by thin-layer chromatography and recrystallization to constant specific radioactivity. After sonification of the cells the postulated 17beta-hydroxysteroid dehydrogenase activity was recovered in the 105 000 g supernatant. The enzyme was enriched by gel filtration on Sephadex G-200. It required NAD+ as cofactor. Its activity could be studied photometrically, because there are no further testosterone-netabolites. If S. hydrogenans was cultured in the presence of testosterone, estradiol or 5alphaH-dihydrotestosterone, the activity of 17beta-hydroxysteroid dehydrogenase increased."} {"id": "PMID:179292", "title": "Apo-lipoprotein localization in human atherosclerotic arteries.", "content": "A study documenting the localization in human arteries of apoproteins from human plasma high density (HDL, low density (LDL), and very low density (VLDL) lipoproteins was undertaken in light of their possible roles in the pathogenesis and regression of the atherosclerotic process in man. Apo A-I from HDL, apo B from LDL, apo C-III from VLDL were all localized by immunohistochemical techniques to generally the same areas of athersclerotic lesions. These consisted of certain bands of collagen and elastic fibers in fatty streaks and fibrous plaques, and extracellular pools of neutral lipid in fibrous plaques. Apoproteins were also occasionally present in areas of diffuse intimal thickening in coronary arteries. Extensiveness and frequency of appearance of apo B in atherosclerotic lesions was greatest in type II hyperlipoproteinemics, thus correlating with the plasma apo B levels. Employing an immuno-peroxidase procedure, apo B was localized ultrastructurally in atherosclerotic lesions to the outer surface of spheres ranging in diameter between 250 and 700 A. These spheres, localized predominantly in lipid cores and between collagen bands, were also seen in negatively-stained preparations of arterial extracts which also reacted positively against anti-apo B, SUGGESTING THAT THE SPHERES MAY REPRESENT NATIVE LDL and VLDL. The superimposed localization of apo A-I, apo B, and apo C-III in atherosclerotic lesions suggests that a specific interaction exists between certain lesion components and these apoproteins.", "contents": "Apo-lipoprotein localization in human atherosclerotic arteries. A study documenting the localization in human arteries of apoproteins from human plasma high density (HDL, low density (LDL), and very low density (VLDL) lipoproteins was undertaken in light of their possible roles in the pathogenesis and regression of the atherosclerotic process in man. Apo A-I from HDL, apo B from LDL, apo C-III from VLDL were all localized by immunohistochemical techniques to generally the same areas of athersclerotic lesions. These consisted of certain bands of collagen and elastic fibers in fatty streaks and fibrous plaques, and extracellular pools of neutral lipid in fibrous plaques. Apoproteins were also occasionally present in areas of diffuse intimal thickening in coronary arteries. Extensiveness and frequency of appearance of apo B in atherosclerotic lesions was greatest in type II hyperlipoproteinemics, thus correlating with the plasma apo B levels. Employing an immuno-peroxidase procedure, apo B was localized ultrastructurally in atherosclerotic lesions to the outer surface of spheres ranging in diameter between 250 and 700 A. These spheres, localized predominantly in lipid cores and between collagen bands, were also seen in negatively-stained preparations of arterial extracts which also reacted positively against anti-apo B, SUGGESTING THAT THE SPHERES MAY REPRESENT NATIVE LDL and VLDL. The superimposed localization of apo A-I, apo B, and apo C-III in atherosclerotic lesions suggests that a specific interaction exists between certain lesion components and these apoproteins."} {"id": "PMID:179293", "title": "Rabbits as a model for the study of hyperlipoproteinemia and atherosclerosis.", "content": "Lipoproteins of normal and cholesteremic plasma were compared in New Zealand White (hyperresponder) and Dutch Belt (hyporesponder) rabbits. Three major differences were observed between the strains: (1) New Zealand White rabbits developed much higher plasma levels of very low, intermediate, and low density lipoproteins after cholesterol feeding; (2) Dutch Belt rabbits, normal and cholesteremic, had higher ratios of the more dense high density lipoproteins HDL3 (d 1.125-1.20 g/ml) to the less dense HDL2 (d 1.081-1.125 g/ml); (3) cholesteremic Dutch Belt rabbits had higher plasma levels of the more dense HDL3 subfraction than did cholesteremic New Zealand White rabbits. Cholesteremic very low density lipoproteins of both strains are large particles of beta electrophoretic mobility that are rich in cholesteryl esters and an arginine-rich apolipoprotein(s). The intermediate and low density lipoprotein fractions were similarly altered in composition, although the proportion of arginine-rich protein to total protein was ledd than in the very low density fraction. Although the high density lipoproteins were greatly decreased in concentration in cholesteremic plasma, no major changes in their apolipoproteins were seen in either strain of rabbits. The major high density apolipoprotein of rabbits occurs in two electrophoretically separable forms and is similar to human apo A-I. Six minor apolipoproteins were isolated from the high density lipoproteins; some of these occur also in other density fractions.", "contents": "Rabbits as a model for the study of hyperlipoproteinemia and atherosclerosis. Lipoproteins of normal and cholesteremic plasma were compared in New Zealand White (hyperresponder) and Dutch Belt (hyporesponder) rabbits. Three major differences were observed between the strains: (1) New Zealand White rabbits developed much higher plasma levels of very low, intermediate, and low density lipoproteins after cholesterol feeding; (2) Dutch Belt rabbits, normal and cholesteremic, had higher ratios of the more dense high density lipoproteins HDL3 (d 1.125-1.20 g/ml) to the less dense HDL2 (d 1.081-1.125 g/ml); (3) cholesteremic Dutch Belt rabbits had higher plasma levels of the more dense HDL3 subfraction than did cholesteremic New Zealand White rabbits. Cholesteremic very low density lipoproteins of both strains are large particles of beta electrophoretic mobility that are rich in cholesteryl esters and an arginine-rich apolipoprotein(s). The intermediate and low density lipoprotein fractions were similarly altered in composition, although the proportion of arginine-rich protein to total protein was ledd than in the very low density fraction. Although the high density lipoproteins were greatly decreased in concentration in cholesteremic plasma, no major changes in their apolipoproteins were seen in either strain of rabbits. The major high density apolipoprotein of rabbits occurs in two electrophoretically separable forms and is similar to human apo A-I. Six minor apolipoproteins were isolated from the high density lipoproteins; some of these occur also in other density fractions."} {"id": "PMID:179294", "title": "Turnover and aortic uptake of very low density lipoproteins (VLDL) from hypercholesteremic rabbits as a model for testing antiatherosclerotic compounds.", "content": "VLDL from hypercholesteremic (HC) rabbits display features which are suggestive of inherent atherogenicity. The lipid composition, compared to that of control VLDL, shows an enrichment of cholesterol esters, which have a very high 18:1/18:2 ratio in their fatty acids, and an increased sphingomyelin content, with decreased PC/Sph ratio. This lipid composition is very similar to that of the atherosclerotic plaqua. Apoprotein peptides of HC VLDL show a predominance of arg-rich proteins, similar to human conditions (Type III hyperlipoproteinemia and hypothyroidism) characterized by early and severe atherosclerosis. Turnover of 125I-labelled HC VLDL is significantly slower than that of control VLDL, both when the lipoprotein is injected into the donor animals and into controls. Conversion of HC VLDL into lipoproteins of higher density is also very small, as compared to control VLDL. Uptake of radioactivity into the aortic wall after injection is about doubled, as compared to control VLDL, when HC rabbits receive HC VLDL. This experimental model suggests that structural modifications of the HC VLDL make them poorly metabolizable, and possible more akin to the recently described arterial lipoprotein complexing factor (ALCF). Metformin was selected as the test compound, because it has been shown to decrease aortic and liver lipid accumulation in cholesterol fed rabbits, while only slightly affecting plasma cholesterol levels. VLDL from rabbits fed cholesterol and metformin (HC+Met), while still enriched in cholesterol esters, have a higher protein content, less sphingomyelin and more phosphatidylethanolamine and phosphatidylinositol than HC VLDL, while fatty acid composition of cholesterol esters does not differ. Turnover of HC+Met VLDL is extremely rapid, with a t1/2 even shorter than that of control VLDL.", "contents": "Turnover and aortic uptake of very low density lipoproteins (VLDL) from hypercholesteremic rabbits as a model for testing antiatherosclerotic compounds. VLDL from hypercholesteremic (HC) rabbits display features which are suggestive of inherent atherogenicity. The lipid composition, compared to that of control VLDL, shows an enrichment of cholesterol esters, which have a very high 18:1/18:2 ratio in their fatty acids, and an increased sphingomyelin content, with decreased PC/Sph ratio. This lipid composition is very similar to that of the atherosclerotic plaqua. Apoprotein peptides of HC VLDL show a predominance of arg-rich proteins, similar to human conditions (Type III hyperlipoproteinemia and hypothyroidism) characterized by early and severe atherosclerosis. Turnover of 125I-labelled HC VLDL is significantly slower than that of control VLDL, both when the lipoprotein is injected into the donor animals and into controls. Conversion of HC VLDL into lipoproteins of higher density is also very small, as compared to control VLDL. Uptake of radioactivity into the aortic wall after injection is about doubled, as compared to control VLDL, when HC rabbits receive HC VLDL. This experimental model suggests that structural modifications of the HC VLDL make them poorly metabolizable, and possible more akin to the recently described arterial lipoprotein complexing factor (ALCF). Metformin was selected as the test compound, because it has been shown to decrease aortic and liver lipid accumulation in cholesterol fed rabbits, while only slightly affecting plasma cholesterol levels. VLDL from rabbits fed cholesterol and metformin (HC+Met), while still enriched in cholesterol esters, have a higher protein content, less sphingomyelin and more phosphatidylethanolamine and phosphatidylinositol than HC VLDL, while fatty acid composition of cholesterol esters does not differ. Turnover of HC+Met VLDL is extremely rapid, with a t1/2 even shorter than that of control VLDL."} {"id": "PMID:179295", "title": "High volume screening procedures for hypobetalipoproteinemic activity in rats.", "content": "We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.", "contents": "High volume screening procedures for hypobetalipoproteinemic activity in rats. We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol."} {"id": "PMID:179296", "title": "Biological activity of a hypobetalipoproteinemic agent.", "content": "A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.", "contents": "Biological activity of a hypobetalipoproteinemic agent. A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons."} {"id": "PMID:179297", "title": "Nonisotopic method for estimating cholesterogenesis in the rat.", "content": "Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) mald rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HC l had no significant effect, while clofibrate or the combination with colestipated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis.", "contents": "Nonisotopic method for estimating cholesterogenesis in the rat. Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) mald rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HC l had no significant effect, while clofibrate or the combination with colestipated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis."} {"id": "PMID:179298", "title": "Inbred mice and their hypbrids as an animal model for atherosclerosis research.", "content": "1. The inbred strain of mouse is a relatively inexpensive and easily controlled animal that produces consistent results within each of the P1, P2, F1, F2, B1 and B2 generations. 2. The mother and father exert an equal influence on the development of fatty deposits in the aortic sinus wall and on serum total cholesterol levels. 3. Different strains of inbred mice react to the high-fat, high-cholesterol diet in different ways. 4. The control mice of the CBA/J (P2) strain had significantly lower values of serum total cholesterol and size of the largest lesion at some weeks than the control mice of the C57BR/cdJ and F1, F2, B1 and B2 generations. 5. The experiments indicate a multifactorial (polygenic) system of inheritance.", "contents": "Inbred mice and their hypbrids as an animal model for atherosclerosis research. 1. The inbred strain of mouse is a relatively inexpensive and easily controlled animal that produces consistent results within each of the P1, P2, F1, F2, B1 and B2 generations. 2. The mother and father exert an equal influence on the development of fatty deposits in the aortic sinus wall and on serum total cholesterol levels. 3. Different strains of inbred mice react to the high-fat, high-cholesterol diet in different ways. 4. The control mice of the CBA/J (P2) strain had significantly lower values of serum total cholesterol and size of the largest lesion at some weeks than the control mice of the C57BR/cdJ and F1, F2, B1 and B2 generations. 5. The experiments indicate a multifactorial (polygenic) system of inheritance."} {"id": "PMID:179299", "title": "The nonhuman primates as models for studying human atherosclerosis: studies on the chimpanzee, the baboon and the rhesus macacus.", "content": "There is no dearth of experimental techniques for producing the hyperlipoproteinemia resulting in atherosclerotic complications and for myocardial infarction in the non human primates. Most of the recent experiments which have given information of great value have been studied with relatively expensive animals for a long period of time up to 6-7 years. It is evident that no animal model perfectly duplicates the human disease or satisfies all desirable requirements. The chimpanzees, representatives of the New World monkeys, have circulating plasma lipoproteins identical to man in composition as well as in function. The results reported above indicate that the compositional changes of chimpanzee plasma lipoproteins in response to dietary changes reflect the appearance of type II and type IV hyperlipoproteinemia similar to the human disease. Moreover, there are more indications about the existence of genotype II a in the chimpanzee, and also on the influence of stress on the plasma lipids, so that the developed intimal lesions similar to the human pathology are in this sense multifactorially influenced. From a phylogenetic point of view the chimpanzee is closer to man than any other non human primate. Furthermore, the chimpanzee lipoproteins are useful models for understanding the relationship between function and structure of the plasma lipoproteins in health and disease. Baboon and rhesus monkeys show similar results, but more differences to the human lipoproteins in health and disease were observed. At present it appears that the most useful models of human atherosclerosis are those induced in the non human primates, especially in the chimpanzee.", "contents": "The nonhuman primates as models for studying human atherosclerosis: studies on the chimpanzee, the baboon and the rhesus macacus. There is no dearth of experimental techniques for producing the hyperlipoproteinemia resulting in atherosclerotic complications and for myocardial infarction in the non human primates. Most of the recent experiments which have given information of great value have been studied with relatively expensive animals for a long period of time up to 6-7 years. It is evident that no animal model perfectly duplicates the human disease or satisfies all desirable requirements. The chimpanzees, representatives of the New World monkeys, have circulating plasma lipoproteins identical to man in composition as well as in function. The results reported above indicate that the compositional changes of chimpanzee plasma lipoproteins in response to dietary changes reflect the appearance of type II and type IV hyperlipoproteinemia similar to the human disease. Moreover, there are more indications about the existence of genotype II a in the chimpanzee, and also on the influence of stress on the plasma lipids, so that the developed intimal lesions similar to the human pathology are in this sense multifactorially influenced. From a phylogenetic point of view the chimpanzee is closer to man than any other non human primate. Furthermore, the chimpanzee lipoproteins are useful models for understanding the relationship between function and structure of the plasma lipoproteins in health and disease. Baboon and rhesus monkeys show similar results, but more differences to the human lipoproteins in health and disease were observed. At present it appears that the most useful models of human atherosclerosis are those induced in the non human primates, especially in the chimpanzee."} {"id": "PMID:179301", "title": "The influence of some dietary factors and/or treadmill exercise on rat and chicken tissue lipids and serum lipoproteins.", "content": "Four different experiments, one with cockerels and three with rats, are described which relate to the effect of dietary factors and/or exercise on serum and liver lipids as well as on serum lipoproteins. Several classes of lipoproteins were isolated by preparative ultracentrifugation, and their purity assessed by gel electrophoresis. The lipid composition and protein content of serum lipoproteins and tissue were also determined. Dietary cholesterol produced an enormous increase (200 fold) in serum very low density lipoproteins in cockerels. This lipoprotein was apparently of very large particle size because it failed to penetrate the spacer gel during disc electrophoresis. In rats fed a cholesterol-supplemented diet, the increase in very low and low density lipoproteins was relatively insignificant in comparison with the cockerels. However, in both species, the liver was overloaded with cholesterol. Further, the serum high density lipoproteins, HDL2 were greatly diminished in both species as a result of cholesterol ingestion for 7 weeks. As a possible explanation for these related observations, it was proposed that HDL2 was utilized in the formation of cellular membranes by cholesterol-burdened, hyperplastic livers. A very high level of dietary corn oil (40% by weight) caused drastic changes in rat liver lipid levels and in serum lipoprotein profiles. Specifically, liver cholesterol and triglycerides were increased about 200% over normal. In another experiment, tissue lipids and serum lipoprotein levels were determined in treadmill-exercised rats and in sedentary controls. Two levels (4 and 40%) of a fat mixture (1:1, hydrogenated coconut oil: corn oil) were used in this study. The serum cholesterol was unchanged in the 4 groups, while the serum triglycerides were reduced in exercised rats given 4% but not 40% fat as compared to respective controls. Rats fed 40% fat and exercised had near normal levels of liver lipids which was in sharp contrast to their sedentary controls. The low denstiy lipoproteins were surprisingly higher in exercised rats given high fat than in sedentary controls. It was suggested that the direct synthesis of these lipoproteins by the liver may be necessitated under unusual conditions. In conclusion, considering the central role of liver in lipid and lipoprotein metabolism greater attention should be focused on this organ in future experiments on the control of hyperlipoproteinemia.", "contents": "The influence of some dietary factors and/or treadmill exercise on rat and chicken tissue lipids and serum lipoproteins. Four different experiments, one with cockerels and three with rats, are described which relate to the effect of dietary factors and/or exercise on serum and liver lipids as well as on serum lipoproteins. Several classes of lipoproteins were isolated by preparative ultracentrifugation, and their purity assessed by gel electrophoresis. The lipid composition and protein content of serum lipoproteins and tissue were also determined. Dietary cholesterol produced an enormous increase (200 fold) in serum very low density lipoproteins in cockerels. This lipoprotein was apparently of very large particle size because it failed to penetrate the spacer gel during disc electrophoresis. In rats fed a cholesterol-supplemented diet, the increase in very low and low density lipoproteins was relatively insignificant in comparison with the cockerels. However, in both species, the liver was overloaded with cholesterol. Further, the serum high density lipoproteins, HDL2 were greatly diminished in both species as a result of cholesterol ingestion for 7 weeks. As a possible explanation for these related observations, it was proposed that HDL2 was utilized in the formation of cellular membranes by cholesterol-burdened, hyperplastic livers. A very high level of dietary corn oil (40% by weight) caused drastic changes in rat liver lipid levels and in serum lipoprotein profiles. Specifically, liver cholesterol and triglycerides were increased about 200% over normal. In another experiment, tissue lipids and serum lipoprotein levels were determined in treadmill-exercised rats and in sedentary controls. Two levels (4 and 40%) of a fat mixture (1:1, hydrogenated coconut oil: corn oil) were used in this study. The serum cholesterol was unchanged in the 4 groups, while the serum triglycerides were reduced in exercised rats given 4% but not 40% fat as compared to respective controls. Rats fed 40% fat and exercised had near normal levels of liver lipids which was in sharp contrast to their sedentary controls. The low denstiy lipoproteins were surprisingly higher in exercised rats given high fat than in sedentary controls. It was suggested that the direct synthesis of these lipoproteins by the liver may be necessitated under unusual conditions. In conclusion, considering the central role of liver in lipid and lipoprotein metabolism greater attention should be focused on this organ in future experiments on the control of hyperlipoproteinemia."} {"id": "PMID:179302", "title": "Mechanism of inhibition of cholesterol uptake by the arterial wall.", "content": "Experiments have been described dealing with lipid synthesis and cholesterol uptake in perfused human and pig coronary arteries, rabbit aortas, and with the inhibitory effect of 7-ketocholesterol on cholesterol uptake in these preparations and in rabbits in vivo. Human and pig coronary arteries failed to synthesize cholesterol in vitro. 7-ketocholesterol inhibited cholesterol uptake in human coronary arteries and aortas of pigs and rabbits in vitro and by rabbit aortas in vivo. The inhibitory effect in vivo could only be shown after repeated i.v. injections of 7-ketocholesterol after solubilizing the steroid with bile sale (Na-glycocholate). Although 7-ketocholesterol was absorbed from the G.I. tract, gastric feeding of the bile salt steroid complex was ineffective, probably because of inadequate blood levels of 7-ketocholesterol achieved. The metabolic fate of 7-ketocholesterol and the nature of its effect on cholesterol are discussed. It is not likely that inhibition of HMG-CoA reductase is responsible for the inhibition of cholesterol uptake. The possibility was discussed that both cholesterol and 7-ketocholesterol actively compete for identical and specific binding sites or that an increase in 7-ketocholesterol in plasma leads to an increase in intracellular concentrations of this steroid thus inhibiting cholesterol transfer across the cell membrane. However definite conclusions on the nature of inhibition must await further experimentation.", "contents": "Mechanism of inhibition of cholesterol uptake by the arterial wall. Experiments have been described dealing with lipid synthesis and cholesterol uptake in perfused human and pig coronary arteries, rabbit aortas, and with the inhibitory effect of 7-ketocholesterol on cholesterol uptake in these preparations and in rabbits in vivo. Human and pig coronary arteries failed to synthesize cholesterol in vitro. 7-ketocholesterol inhibited cholesterol uptake in human coronary arteries and aortas of pigs and rabbits in vitro and by rabbit aortas in vivo. The inhibitory effect in vivo could only be shown after repeated i.v. injections of 7-ketocholesterol after solubilizing the steroid with bile sale (Na-glycocholate). Although 7-ketocholesterol was absorbed from the G.I. tract, gastric feeding of the bile salt steroid complex was ineffective, probably because of inadequate blood levels of 7-ketocholesterol achieved. The metabolic fate of 7-ketocholesterol and the nature of its effect on cholesterol are discussed. It is not likely that inhibition of HMG-CoA reductase is responsible for the inhibition of cholesterol uptake. The possibility was discussed that both cholesterol and 7-ketocholesterol actively compete for identical and specific binding sites or that an increase in 7-ketocholesterol in plasma leads to an increase in intracellular concentrations of this steroid thus inhibiting cholesterol transfer across the cell membrane. However definite conclusions on the nature of inhibition must await further experimentation."} {"id": "PMID:179303", "title": "Lipoprotein uptake and degradation by cultured human arterial smooth muscle cells.", "content": "The multipotential smooth muscle cell (SMC) is the predominant cell in intima and media of large arteries, proliferating eraly in the development of atheroma to become the lipid-laden foam cell. Thomogeneous cultures of human SMA have now been successfully grown from explants of normal pieces of artery obtained during surgery. In contrast to previous results with rat SMC, human SMC preferentially bind and take up large, lipid-rich lipoproteins (I125 labeled low density and very low denstiy lipoproteins) (LDL and VLDL), in comparison to smaller, high density lipoproteins (HDL). This species selectivity appears to be related to differences both in cells and in lipoproteins. Specific binding of lipoproteins by SMC, analyzed by release of radioactive protein from the cell surfaces by trypsin, accounted for approximately hal of the protein radioactivity associated with the cell layer during the first few hours of incubation. Specific binding appears to be related to the presence of apoprotein B on the lipoproteins. Lipoproteins progressively accumulate within cells as a function of incubation time. Lipoprotein degradation, assessed by appearance of TCA soluble, non-iodide radioactivity in the incubation medium, increased rapidly after an initial delay of 2 to 4 hours. Cells grown under hypoxic (5% O2) conditions instead of the usual room air showed impaired degradation of lipoproteins. These results suggest that there are receptors on arterial SMC, highly specific for different lipoproteins (as shown for skin fibroblasts). This tissue culture system may be useful for assessment of the effects of a variety of hormones, metabolites, and drugs on the handling of lipoproteins by arterial smooth muscle cells.", "contents": "Lipoprotein uptake and degradation by cultured human arterial smooth muscle cells. The multipotential smooth muscle cell (SMC) is the predominant cell in intima and media of large arteries, proliferating eraly in the development of atheroma to become the lipid-laden foam cell. Thomogeneous cultures of human SMA have now been successfully grown from explants of normal pieces of artery obtained during surgery. In contrast to previous results with rat SMC, human SMC preferentially bind and take up large, lipid-rich lipoproteins (I125 labeled low density and very low denstiy lipoproteins) (LDL and VLDL), in comparison to smaller, high density lipoproteins (HDL). This species selectivity appears to be related to differences both in cells and in lipoproteins. Specific binding of lipoproteins by SMC, analyzed by release of radioactive protein from the cell surfaces by trypsin, accounted for approximately hal of the protein radioactivity associated with the cell layer during the first few hours of incubation. Specific binding appears to be related to the presence of apoprotein B on the lipoproteins. Lipoproteins progressively accumulate within cells as a function of incubation time. Lipoprotein degradation, assessed by appearance of TCA soluble, non-iodide radioactivity in the incubation medium, increased rapidly after an initial delay of 2 to 4 hours. Cells grown under hypoxic (5% O2) conditions instead of the usual room air showed impaired degradation of lipoproteins. These results suggest that there are receptors on arterial SMC, highly specific for different lipoproteins (as shown for skin fibroblasts). This tissue culture system may be useful for assessment of the effects of a variety of hormones, metabolites, and drugs on the handling of lipoproteins by arterial smooth muscle cells."} {"id": "PMID:179305", "title": "Phylogenetic variability of serum lipids and lipoproteins in non-human primates fed diets with different contents of dietary cholesterol.", "content": "The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes.", "contents": "Phylogenetic variability of serum lipids and lipoproteins in non-human primates fed diets with different contents of dietary cholesterol. The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes."} {"id": "PMID:179309", "title": "Femoral neck fractures in elderly women: a prospective study.", "content": "Fifty female patients admitted to the orthopaedic unit at the Royal East Sussex Hospital with a fracture of the proximal femur were followed prospectively. Forty-six of these patients had concurrent medical problems. Six patients required resettlement after recovery from their fracture, and of the twenty-six returning home, eighteen required support from social services. The function of the geriatric/orthopaedic unit is reviewed and it is suggested that the combined unit is of value to all elderly patients with a proximal fracture of the femur.", "contents": "Femoral neck fractures in elderly women: a prospective study. Fifty female patients admitted to the orthopaedic unit at the Royal East Sussex Hospital with a fracture of the proximal femur were followed prospectively. Forty-six of these patients had concurrent medical problems. Six patients required resettlement after recovery from their fracture, and of the twenty-six returning home, eighteen required support from social services. The function of the geriatric/orthopaedic unit is reviewed and it is suggested that the combined unit is of value to all elderly patients with a proximal fracture of the femur."} {"id": "PMID:179312", "title": "In defense of the dust count technique.", "content": "NISOH has recommended a Standard for Occupational Exposure to crystalline silica to OSHA with documentation based on dust count studies relating to health effects. This standard dictates sampling by mass respirable method only. A dual standard as in ACGIH-TLV list should be promulgated by OSHA which includes the dust count standard.", "contents": "In defense of the dust count technique. NISOH has recommended a Standard for Occupational Exposure to crystalline silica to OSHA with documentation based on dust count studies relating to health effects. This standard dictates sampling by mass respirable method only. A dual standard as in ACGIH-TLV list should be promulgated by OSHA which includes the dust count standard."} {"id": "PMID:179314", "title": "The effects of a 20-week nutritional insult on the skeletal development of Cebus albifrons during the 1st year of life.", "content": "Using an atlas constructed from records of a group of normal monkeys in the same colony, the effects of a 20-week low-calorie or low-protein nutritional insult on skeletal development were determined. The most significantly retarded sites were the late-forming ossifications (epiphyses, sesamoids, and tuberosites). A general increase in ossification anomalies and in individual variation was evident. The similarity of these findings to studies previously reported for man indicates the utility of nonhuman primate models for the further study of nutritional deficiency.", "contents": "The effects of a 20-week nutritional insult on the skeletal development of Cebus albifrons during the 1st year of life. Using an atlas constructed from records of a group of normal monkeys in the same colony, the effects of a 20-week low-calorie or low-protein nutritional insult on skeletal development were determined. The most significantly retarded sites were the late-forming ossifications (epiphyses, sesamoids, and tuberosites). A general increase in ossification anomalies and in individual variation was evident. The similarity of these findings to studies previously reported for man indicates the utility of nonhuman primate models for the further study of nutritional deficiency."} {"id": "PMID:179310", "title": "Immunosuppressive effect of intra-lymphatic irradiation.", "content": "The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation.", "contents": "Immunosuppressive effect of intra-lymphatic irradiation. The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation."} {"id": "PMID:179315", "title": "Further heterogeneity of the oral-facial-digital syndromes.", "content": "Two patients with polysyndactyly of the halluces and typical features of oral-facial-digital syndrome, type I (OFS I), are described. Previously, bilateral hallucal polysyndactyly was considered to be a distinctive feature of OFD II, Mohr syndrome. The original classification of OFD II was based on clinical similarities between the affected members of the Mohr-Claussen kindred and the two siblings described by Rimoin and Edgerton. Review of these cases deomnstrates important clinical differences, so that justification for the original classification of OFD II is questioned. Retrospectively, a small number of individuals have been considered to have had OFD II, but on review these cases appear to represent a clinically heterogeneous group of disorders.", "contents": "Further heterogeneity of the oral-facial-digital syndromes. Two patients with polysyndactyly of the halluces and typical features of oral-facial-digital syndrome, type I (OFS I), are described. Previously, bilateral hallucal polysyndactyly was considered to be a distinctive feature of OFD II, Mohr syndrome. The original classification of OFD II was based on clinical similarities between the affected members of the Mohr-Claussen kindred and the two siblings described by Rimoin and Edgerton. Review of these cases deomnstrates important clinical differences, so that justification for the original classification of OFD II is questioned. Retrospectively, a small number of individuals have been considered to have had OFD II, but on review these cases appear to represent a clinically heterogeneous group of disorders."} {"id": "PMID:179317", "title": "A review of macromolecular transport and secretion at the cellular level.", "content": "This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role.", "contents": "A review of macromolecular transport and secretion at the cellular level. This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role."} {"id": "PMID:179318", "title": "Benign breast tumor and estrogenic hormones: a population-based retrospective study.", "content": "Histories of the usage of oral contraceptives and other estrogens were obtained from 320 women 20-49 years of age who had pathologically confirmed diagnoses of benign breast disease made at Washington County Hospital in Hagerstown, Maryland, during the period 1968 through 1972. Similar histories were obtained from 320 controls matched for race, sex, age, residence in county, and willingness to participate in a health survey. No association could be found between oral contraceptive usage and benign breast tumor. The use of other estrogens, notably diethylstilbestrol, was significantly related to the presence of benign breast disease.", "contents": "Benign breast tumor and estrogenic hormones: a population-based retrospective study. Histories of the usage of oral contraceptives and other estrogens were obtained from 320 women 20-49 years of age who had pathologically confirmed diagnoses of benign breast disease made at Washington County Hospital in Hagerstown, Maryland, during the period 1968 through 1972. Similar histories were obtained from 320 controls matched for race, sex, age, residence in county, and willingness to participate in a health survey. No association could be found between oral contraceptive usage and benign breast tumor. The use of other estrogens, notably diethylstilbestrol, was significantly related to the presence of benign breast disease."} {"id": "PMID:179319", "title": "Selection of cell culture systems for virus isolation.", "content": "A survey of cell culture systems for virus isolation is presented. Because there is not single cell culture system which will support the many viruses that may be encountered in clinical specimens, the characteristics and susceptibility of primary, diploid, and continuous cell cultures are reviewed. The primary cell culture system should be susceptible to infection with myxoviruses, paramyxoviruses, adenoviruses, and Coxsackie B viruses, since these are not consistently recognized in diploid cell cultures. Conversely, rhinoviruses, cytomegalovirus and varicella-zoster virus may be isolated only in diploid cell cultures. Upon consideration of expected viruses, and cell cultures available for isolation of these, one can choose a combination of a primary and a diploid cell system for virus isolation which will assure detection of most human virus groups known. The usefulness of continuous cell culture systems is generally limited to a very few specific viruses.", "contents": "Selection of cell culture systems for virus isolation. A survey of cell culture systems for virus isolation is presented. Because there is not single cell culture system which will support the many viruses that may be encountered in clinical specimens, the characteristics and susceptibility of primary, diploid, and continuous cell cultures are reviewed. The primary cell culture system should be susceptible to infection with myxoviruses, paramyxoviruses, adenoviruses, and Coxsackie B viruses, since these are not consistently recognized in diploid cell cultures. Conversely, rhinoviruses, cytomegalovirus and varicella-zoster virus may be isolated only in diploid cell cultures. Upon consideration of expected viruses, and cell cultures available for isolation of these, one can choose a combination of a primary and a diploid cell system for virus isolation which will assure detection of most human virus groups known. The usefulness of continuous cell culture systems is generally limited to a very few specific viruses."} {"id": "PMID:179320", "title": "Sexually transmissible diseases.", "content": "There is a widespread recrudescence of venereal disease. The possible reasons for this are discussed. Each disease is then considered from the viewpoints of clinical course, diagnosis, and treatment. Treatment failures are discussed in detail, immunity is covered, and recommendations for the future conclude the presentation.", "contents": "Sexually transmissible diseases. There is a widespread recrudescence of venereal disease. The possible reasons for this are discussed. Each disease is then considered from the viewpoints of clinical course, diagnosis, and treatment. Treatment failures are discussed in detail, immunity is covered, and recommendations for the future conclude the presentation."} {"id": "PMID:179321", "title": "An experimental model for disseminated herpesvirus infection of the neonate.", "content": "Pregnant mice at 10 days of gestation were more susceptible to vaginal inoculation with herpesvirus, type 2, than were nonpregnant mice. This mouse model system also was used to compare delivery through a birth canal contaminated with herpesvirus, type 2, to delivery after maternal paranteral inoculation by the same virus. Approximately 26 per cent of newborn mice either died or had evidence of disseminated herpesvirus infections after delivering through a vagina inoculated with herpesvirus, whereas only 4 per cent of newborn mice died after subcutaneous inoculation of pregnant animals. Only 1 per cent of neonates delivered of subcutaneously inoculated pregnant mice had any evidence of herpesvirus infection. Pregnant mice immunized to herpesvirus, type 1, had significantly less newborn infection after delivery through a herpesvirus-inoculated birth canal when compared to nonimmunized mice.", "contents": "An experimental model for disseminated herpesvirus infection of the neonate. Pregnant mice at 10 days of gestation were more susceptible to vaginal inoculation with herpesvirus, type 2, than were nonpregnant mice. This mouse model system also was used to compare delivery through a birth canal contaminated with herpesvirus, type 2, to delivery after maternal paranteral inoculation by the same virus. Approximately 26 per cent of newborn mice either died or had evidence of disseminated herpesvirus infections after delivering through a vagina inoculated with herpesvirus, whereas only 4 per cent of newborn mice died after subcutaneous inoculation of pregnant animals. Only 1 per cent of neonates delivered of subcutaneously inoculated pregnant mice had any evidence of herpesvirus infection. Pregnant mice immunized to herpesvirus, type 1, had significantly less newborn infection after delivery through a herpesvirus-inoculated birth canal when compared to nonimmunized mice."} {"id": "PMID:179322", "title": "Progesterone binding in human endometrial carcinomas.", "content": "By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.", "contents": "Progesterone binding in human endometrial carcinomas. By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity."} {"id": "PMID:179323", "title": "Blindness caused by photoreceptor degeneration as a remote effect of cancer.", "content": "Three postmenopausal women developed photoreceptor degeneration one to four months preceding or following discovery of an anaplastic tumor. Two patients had transitory visual obscurations and bizarre visual sensations. Ring scotomas progressed to severe visual field loss. Retinal arteries were markedly narrowed. Electroretinograms revealed almost total absence of response in one patient, and another complained of the recent onset of night blindness. In all three patients severe degeneration of the photoreceptor cells associated with melanophagic activity was shown histologically. In two patients neuropathologic examination from the retinal bipolar cells to the occipital cortex revealed no significant alterations.", "contents": "Blindness caused by photoreceptor degeneration as a remote effect of cancer. Three postmenopausal women developed photoreceptor degeneration one to four months preceding or following discovery of an anaplastic tumor. Two patients had transitory visual obscurations and bizarre visual sensations. Ring scotomas progressed to severe visual field loss. Retinal arteries were markedly narrowed. Electroretinograms revealed almost total absence of response in one patient, and another complained of the recent onset of night blindness. In all three patients severe degeneration of the photoreceptor cells associated with melanophagic activity was shown histologically. In two patients neuropathologic examination from the retinal bipolar cells to the occipital cortex revealed no significant alterations."} {"id": "PMID:179324", "title": "Effect of aspirin and dexamethasone on intraocular pressure in primary uveitis produced by Herpes simplex virus.", "content": "The intracameral injection of New Zealand white male rabbits with type 1 herpes simplex virus produced acute anterior uveitis with biphasic elevation of the intraocular pressure (IOP). The first IOP increase occurred on day 1 and 2 and the second increase on day 8. There was no significant correlation between the IOP changes and multiplication of herpes simplex virus in the uvea and cornea, nor between the IOP changes and histopathologic alteration of the tissue. Aspirin suppressed significantly the first as well as the second IOP elevation, whereas dexamethasone suppressed significantly only the second elevation.", "contents": "Effect of aspirin and dexamethasone on intraocular pressure in primary uveitis produced by Herpes simplex virus. The intracameral injection of New Zealand white male rabbits with type 1 herpes simplex virus produced acute anterior uveitis with biphasic elevation of the intraocular pressure (IOP). The first IOP increase occurred on day 1 and 2 and the second increase on day 8. There was no significant correlation between the IOP changes and multiplication of herpes simplex virus in the uvea and cornea, nor between the IOP changes and histopathologic alteration of the tissue. Aspirin suppressed significantly the first as well as the second IOP elevation, whereas dexamethasone suppressed significantly only the second elevation."} {"id": "PMID:179325", "title": "Optic nerve manifestations of human congenital cytomegalovirus infection.", "content": "A Latin American male and a white female infant who had a cytomegalovirus infection on the first day of life had unilateral optic nerve hypoplasia. A white male infant who had cytomegalovirus isolated at 5 weeks of age had a unilateral partial coloboma of the optic nerve. A 4-month-old black infant with cytomegalovirus infection diagnosed at 2 days of age had a unilateral complete coloboma of the optic nerve associated with microphthalmia. Optic nerve involvement was an important manifestation of this disease.", "contents": "Optic nerve manifestations of human congenital cytomegalovirus infection. A Latin American male and a white female infant who had a cytomegalovirus infection on the first day of life had unilateral optic nerve hypoplasia. A white male infant who had cytomegalovirus isolated at 5 weeks of age had a unilateral partial coloboma of the optic nerve. A 4-month-old black infant with cytomegalovirus infection diagnosed at 2 days of age had a unilateral complete coloboma of the optic nerve associated with microphthalmia. Optic nerve involvement was an important manifestation of this disease."} {"id": "PMID:179326", "title": "Skeletal ossification and the adolescent growth spurt.", "content": "Fourteen ossification events in the hand and wrist were studied in relation to the age of peak growth velocity in body height in fifty-two boys and thirty-six girls. The subjects were aborigines enrolled in a longitudinal growth study. Peak growth velocity and the ossification events occurred in aborigines at about the same ages as in Caucasian children. The results indicate that the ossification events can be used by the orthodontist to assess a child's growth activity. The accelerative phase of the adolescent growth spurt is accompanied by epiphyseal widths reaching diaphyseal widths in the fingers and radius and by ossification of the pisiform and hamate Stage 1. Peak growth velocity occurs at about the time of epiphyseal capping in the fingers and radius and ossification of the sesamoid and hamate Stage 2. The decelerative phase of growth is indicated by epiphyseal union in the third finger, progressively from distal to proximal phalanges, and in the radius. The value of these indicators in orthodontic practice is discussed.", "contents": "Skeletal ossification and the adolescent growth spurt. Fourteen ossification events in the hand and wrist were studied in relation to the age of peak growth velocity in body height in fifty-two boys and thirty-six girls. The subjects were aborigines enrolled in a longitudinal growth study. Peak growth velocity and the ossification events occurred in aborigines at about the same ages as in Caucasian children. The results indicate that the ossification events can be used by the orthodontist to assess a child's growth activity. The accelerative phase of the adolescent growth spurt is accompanied by epiphyseal widths reaching diaphyseal widths in the fingers and radius and by ossification of the pisiform and hamate Stage 1. Peak growth velocity occurs at about the time of epiphyseal capping in the fingers and radius and ossification of the sesamoid and hamate Stage 2. The decelerative phase of growth is indicated by epiphyseal union in the third finger, progressively from distal to proximal phalanges, and in the radius. The value of these indicators in orthodontic practice is discussed."} {"id": "PMID:179327", "title": "Evolution of cytoplasmic fibrillar bodies induced by lead in rat and mouse kidneys.", "content": "Characteristic cytoplasmic and intranuclear fibrillar bodies were produced, within 24 hours, in epithelial cells of the proximal convoluted renal tubules of rats and mice by injecting a single dose of lead acetate either intraperitoneally (100 mug Pb/g) or into the heart (10 mug Pb/g). The frequency of cytoplasmic fibrillar bodies (CFB) rose during the first 4 days following injection of lead and diminished thereafter. Ten days after intracardiac injection of lead no CFB were found; 10 days after intraperitoneal injection, they were still present, though probably in diminished number. Disappearance of CFB may be related to autophagocytosis. Intranuclear fibrillar bodies did not disappear, perhaps because nuclei lack a lysosomal apparatus. Within the first 3 days after injection of lead, clusters or paracrystalline arrays of ferritin molecules were frequently situated in the immediate vicinity of CRB or abutted against CFB; after the third day, little or no ferritin was found near CFB. Intramuscular injection of iron-dextran complex (50 mg Fe/ml) 24 hours prior to intraperitoneal administration of lead did not increase incidence or size of ferritin clusters in the vicinity of CFB in rats. The presence of ferritin near CFB may have been an indirect consequence of inhibition, by lead, of synthesis of heme prosthetic groups.", "contents": "Evolution of cytoplasmic fibrillar bodies induced by lead in rat and mouse kidneys. Characteristic cytoplasmic and intranuclear fibrillar bodies were produced, within 24 hours, in epithelial cells of the proximal convoluted renal tubules of rats and mice by injecting a single dose of lead acetate either intraperitoneally (100 mug Pb/g) or into the heart (10 mug Pb/g). The frequency of cytoplasmic fibrillar bodies (CFB) rose during the first 4 days following injection of lead and diminished thereafter. Ten days after intracardiac injection of lead no CFB were found; 10 days after intraperitoneal injection, they were still present, though probably in diminished number. Disappearance of CFB may be related to autophagocytosis. Intranuclear fibrillar bodies did not disappear, perhaps because nuclei lack a lysosomal apparatus. Within the first 3 days after injection of lead, clusters or paracrystalline arrays of ferritin molecules were frequently situated in the immediate vicinity of CRB or abutted against CFB; after the third day, little or no ferritin was found near CFB. Intramuscular injection of iron-dextran complex (50 mg Fe/ml) 24 hours prior to intraperitoneal administration of lead did not increase incidence or size of ferritin clusters in the vicinity of CFB in rats. The presence of ferritin near CFB may have been an indirect consequence of inhibition, by lead, of synthesis of heme prosthetic groups."} {"id": "PMID:179328", "title": "The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats.", "content": "Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors.", "contents": "The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats. Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors."} {"id": "PMID:179329", "title": "Angiotensin II binding to renal glomeruli from sodium-loaded and sodium-depleted rats.", "content": "125I-labeled angiotensin II (125I-labeled AII) and [3H]angiotensin II ([3H]AII) bind specifically to isolated rat glomeruli. Three groups of receptor sites could be defined by the KD value (7.1 +/- 0.3 X 10(-11, 3.4 +/- 0.2 X 10(-10), and 1.6 X 10(-9) M, respectively) and the number of receptor sites (11.6 +/- 1.2, 29.4 +/- 3.9, and 113.8 +/- 3.8 fmol/mg glomerular protein, respectively). Both association and dissociation constants for 125I-labeled AII were greater than those for [3H]AII, but their ratio (KD) remained unchanged. Specificity of binding to these three groups of receptor sites was demonstrated by the following: 1) inhibition of binding of labeled AII by unlabeled hormone or by antagonists; and 2) reversibility of binding, independent of either hormone or receptor degradation. Binding was increased in glomerular preparations from acutely and chronically sodium-loaded rats, compared with glomerular preparations from acutely and chronically sodium-depleted rats. This change in binding resulted from both a change in the number of receptor sites and modification of the affinity of AII for its receptors. KD was higher in preparations from sodium-depleted rats (12.9 +/- 3.3 and 14.6 +/- 3.9 X 10(-11) M in chronically and acutely depleted rats, respectively) than in those from sodium-loaded rats (2.7 +/- 0.2 and 3.9 +/- 1 X 10(-11) M in chronically and acutely sodium-loaded rats, respectively). Changes in the binding of AII to its glomerular receptors could play a role in the adaptation of glomerular filtration rate to the sodium balance.", "contents": "Angiotensin II binding to renal glomeruli from sodium-loaded and sodium-depleted rats. 125I-labeled angiotensin II (125I-labeled AII) and [3H]angiotensin II ([3H]AII) bind specifically to isolated rat glomeruli. Three groups of receptor sites could be defined by the KD value (7.1 +/- 0.3 X 10(-11, 3.4 +/- 0.2 X 10(-10), and 1.6 X 10(-9) M, respectively) and the number of receptor sites (11.6 +/- 1.2, 29.4 +/- 3.9, and 113.8 +/- 3.8 fmol/mg glomerular protein, respectively). Both association and dissociation constants for 125I-labeled AII were greater than those for [3H]AII, but their ratio (KD) remained unchanged. Specificity of binding to these three groups of receptor sites was demonstrated by the following: 1) inhibition of binding of labeled AII by unlabeled hormone or by antagonists; and 2) reversibility of binding, independent of either hormone or receptor degradation. Binding was increased in glomerular preparations from acutely and chronically sodium-loaded rats, compared with glomerular preparations from acutely and chronically sodium-depleted rats. This change in binding resulted from both a change in the number of receptor sites and modification of the affinity of AII for its receptors. KD was higher in preparations from sodium-depleted rats (12.9 +/- 3.3 and 14.6 +/- 3.9 X 10(-11) M in chronically and acutely depleted rats, respectively) than in those from sodium-loaded rats (2.7 +/- 0.2 and 3.9 +/- 1 X 10(-11) M in chronically and acutely sodium-loaded rats, respectively). Changes in the binding of AII to its glomerular receptors could play a role in the adaptation of glomerular filtration rate to the sodium balance."} {"id": "PMID:179330", "title": "Biochemical adaptations in skeletal muscle of trained thyroidectomized rats.", "content": "The cytochrome c concentrations of the different types of skeletal muscle of trained and nontrained normal and thyroidectomized rats were measured. Animals were trained by treadmill running 1 mph, at a 15% incline, 1 h/day, 5 days/wk for at least 12 wk. This training program induced an expected 50% increase in cytochrome c in the high-oxidative fast-twitch red (FTR) and slow-twitch red (STR) fibers and only a 25% increase in the low-oxidative fast-twitch white (FTW) fibers of the normal rats. This same training program caused a greater increase (100%) in the FTR and STR fibers of the thyroidectomized runners and a dramatic 243% increase in the FTW fiber. Even though the thyroidectomy procedure caused a reduction in oxidative capacity of all types of skeletal muscle fibers to about one-half normal, the absolute increase in cytochrome c in the muscles of the trained thyroidectomized animals was essentially the same or greater than that of the normal trained animals. These results indicate that the adaptive response to training of an increased oxidative capacity in skeletal muscle occurs in the absence of normal thyroid function. They also suggest that the exercise bouts of the thyroidectomized animals were performed with a relatively greater involvement of the FTW muscle fibers.", "contents": "Biochemical adaptations in skeletal muscle of trained thyroidectomized rats. The cytochrome c concentrations of the different types of skeletal muscle of trained and nontrained normal and thyroidectomized rats were measured. Animals were trained by treadmill running 1 mph, at a 15% incline, 1 h/day, 5 days/wk for at least 12 wk. This training program induced an expected 50% increase in cytochrome c in the high-oxidative fast-twitch red (FTR) and slow-twitch red (STR) fibers and only a 25% increase in the low-oxidative fast-twitch white (FTW) fibers of the normal rats. This same training program caused a greater increase (100%) in the FTR and STR fibers of the thyroidectomized runners and a dramatic 243% increase in the FTW fiber. Even though the thyroidectomy procedure caused a reduction in oxidative capacity of all types of skeletal muscle fibers to about one-half normal, the absolute increase in cytochrome c in the muscles of the trained thyroidectomized animals was essentially the same or greater than that of the normal trained animals. These results indicate that the adaptive response to training of an increased oxidative capacity in skeletal muscle occurs in the absence of normal thyroid function. They also suggest that the exercise bouts of the thyroidectomized animals were performed with a relatively greater involvement of the FTW muscle fibers."} {"id": "PMID:179331", "title": "Adenosine relaxation of isolated vascular smooth muscle.", "content": "Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by K+. In both cases, adenosine's efficacy decreased with increasing concentrations of the stimulating agent. A high adenosine concentration (1 X 10(-3)M) was necessary to elicit relaxation of completely depolarized (124 mM K+) media strips and equimolar concentrations of aminophylline caused greater relaxation than did adenosine. Adenosine inhibited the Ca2+ dose-response curves of strips stimulated with 20 mM and 30 mM K+ and its effect was dependent on the Ca2+ concentration. Neither 1 X 10(-6)M nor 1 X 10(-4)M adenosine produced any change in the cAMP content of vascular strips. Only at high concentrations did adenosine increase the cAMP content of vascular strips, but the increase was signficantly more than that observed with the same dose of aminophylline. The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in the adenosine-induced relaxation of vascular smooth muscle.", "contents": "Adenosine relaxation of isolated vascular smooth muscle. Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by K+. In both cases, adenosine's efficacy decreased with increasing concentrations of the stimulating agent. A high adenosine concentration (1 X 10(-3)M) was necessary to elicit relaxation of completely depolarized (124 mM K+) media strips and equimolar concentrations of aminophylline caused greater relaxation than did adenosine. Adenosine inhibited the Ca2+ dose-response curves of strips stimulated with 20 mM and 30 mM K+ and its effect was dependent on the Ca2+ concentration. Neither 1 X 10(-6)M nor 1 X 10(-4)M adenosine produced any change in the cAMP content of vascular strips. Only at high concentrations did adenosine increase the cAMP content of vascular strips, but the increase was signficantly more than that observed with the same dose of aminophylline. The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in the adenosine-induced relaxation of vascular smooth muscle."} {"id": "PMID:179332", "title": "Lipolytic activity of swine adipocytes.", "content": "Lipolysis in isolated swine adipocytes was stimulated by epinephrine, dibutyryl cyclic AMP, and weakly by adrenocorticotropin but not by glucagon or cyclic AMP. Theophylline, a phosphodiesterase inhibitor, stimulated lipolysis and greatly enhanced the activity of adrenocorticotropin. The epinephrine-stimulated lipolytic activity, expressed on a tissue or cell volume basis, was greatest at 25 days postpartum, whereas, expressed on a cell basis, the activity was maximal at day 80. Regardless of the mode of expression, the activity at day 150 was low. Cells from younger animals were more sensitive to epinephrine than cells from older animals.", "contents": "Lipolytic activity of swine adipocytes. Lipolysis in isolated swine adipocytes was stimulated by epinephrine, dibutyryl cyclic AMP, and weakly by adrenocorticotropin but not by glucagon or cyclic AMP. Theophylline, a phosphodiesterase inhibitor, stimulated lipolysis and greatly enhanced the activity of adrenocorticotropin. The epinephrine-stimulated lipolytic activity, expressed on a tissue or cell volume basis, was greatest at 25 days postpartum, whereas, expressed on a cell basis, the activity was maximal at day 80. Regardless of the mode of expression, the activity at day 150 was low. Cells from younger animals were more sensitive to epinephrine than cells from older animals."} {"id": "PMID:179333", "title": "EEG sleep changes as predictors in depression.", "content": "The authors conducted a study of 18 depressed patients to see whether EEG sleep measurements might provide a predictive tool for response to antidepressant medication. They found that although the sedative characteristics of amitriptyline did not differentiate good responders from poor responders until the third week of drug treatment, the good responders showed significant increases in REM latency, decreases in REM sleep time, decreases in REM sleep percent, and decreases in REM activity after only 2 nights of drug treatment.", "contents": "EEG sleep changes as predictors in depression. The authors conducted a study of 18 depressed patients to see whether EEG sleep measurements might provide a predictive tool for response to antidepressant medication. They found that although the sedative characteristics of amitriptyline did not differentiate good responders from poor responders until the third week of drug treatment, the good responders showed significant increases in REM latency, decreases in REM sleep time, decreases in REM sleep percent, and decreases in REM activity after only 2 nights of drug treatment."} {"id": "PMID:179335", "title": "Loss of colonic haustration in progressive systemic sclerosis.", "content": "Complete loss of colonic haustration was observed in six cases of progressive systemic sclerosis. Varying degrees of haustral loss or sacculation were noted in twelve others. An increase in colonic length was characteristic and, occasionally, there was slight to moderate generalized dilatation. Correlation of these findings with the microscopic appearance of the colon showed that muscular atrophy and fibrous replacement were consistent findings, varying in degree. Although the data are insufficient to permit definite conclusions, it is suggested that these changes may be responsible for colonic lengthening and loss of haustration. Attention is drawn to the importance of not confusing this appearance with other conditions, particularly chronic ulcerative colitis.", "contents": "Loss of colonic haustration in progressive systemic sclerosis. Complete loss of colonic haustration was observed in six cases of progressive systemic sclerosis. Varying degrees of haustral loss or sacculation were noted in twelve others. An increase in colonic length was characteristic and, occasionally, there was slight to moderate generalized dilatation. Correlation of these findings with the microscopic appearance of the colon showed that muscular atrophy and fibrous replacement were consistent findings, varying in degree. Although the data are insufficient to permit definite conclusions, it is suggested that these changes may be responsible for colonic lengthening and loss of haustration. Attention is drawn to the importance of not confusing this appearance with other conditions, particularly chronic ulcerative colitis."} {"id": "PMID:179336", "title": "Roentgen findings in aorto-enteric fistulae.", "content": "Six cases of aorto-enteric fistulas are discussed. In three patients the aorta ruptured into the duodenum and in three there was rupture into the esophagus. Aorto-enteric fistula is usually caused by atherosclerosis, but may also be due to syphilis or tuberculosis. Following insertion of an aortic graft, fistula is usually the result of breakdown of the anastomosis. Gastrointestinal bleeding usually heralds the problem. The roentgen signs of rupture are pressure on the esophagus or intestine, bleeding into the wall or lumen, and demonstration of the fistula. The abnormal connection may not be demonstrable by aortography. These signs permit early diagnosis and subsequent possible life saving surgical correction.", "contents": "Roentgen findings in aorto-enteric fistulae. Six cases of aorto-enteric fistulas are discussed. In three patients the aorta ruptured into the duodenum and in three there was rupture into the esophagus. Aorto-enteric fistula is usually caused by atherosclerosis, but may also be due to syphilis or tuberculosis. Following insertion of an aortic graft, fistula is usually the result of breakdown of the anastomosis. Gastrointestinal bleeding usually heralds the problem. The roentgen signs of rupture are pressure on the esophagus or intestine, bleeding into the wall or lumen, and demonstration of the fistula. The abnormal connection may not be demonstrable by aortography. These signs permit early diagnosis and subsequent possible life saving surgical correction."} {"id": "PMID:179337", "title": "Multiple benign ureteral fibrous polyps.", "content": "Two cases of benign polyps of the ureter are reported with emphasis on the uroradiological features and methods of evaluation in the diagnosis of benign mesodermal tumors of the ureter. The apparently excellent results from conservative surgery make the recognition and preoperative roentgenologic diagnosis of this entity mandatory.", "contents": "Multiple benign ureteral fibrous polyps. Two cases of benign polyps of the ureter are reported with emphasis on the uroradiological features and methods of evaluation in the diagnosis of benign mesodermal tumors of the ureter. The apparently excellent results from conservative surgery make the recognition and preoperative roentgenologic diagnosis of this entity mandatory."} {"id": "PMID:179338", "title": "Cavitating lung nodules and pneumothorax in children with metastatic Wilms' tumor.", "content": "Lung metastases evolved into large thin-walled cysts in two children with Wilms' tumor. Histologic examination of one lesion suggested that invasion of a small bronchus or bronchiole, leading to ball-valve obstruction, was responsible. One patient also experienced recurrent pneumothorax, probably on the same basis. The formation of thin-walled cysts has not previously been observed with metastatic Wilms' tumor. Pneumothorax is a rare complication of metastatic Wilms' tumor.", "contents": "Cavitating lung nodules and pneumothorax in children with metastatic Wilms' tumor. Lung metastases evolved into large thin-walled cysts in two children with Wilms' tumor. Histologic examination of one lesion suggested that invasion of a small bronchus or bronchiole, leading to ball-valve obstruction, was responsible. One patient also experienced recurrent pneumothorax, probably on the same basis. The formation of thin-walled cysts has not previously been observed with metastatic Wilms' tumor. Pneumothorax is a rare complication of metastatic Wilms' tumor."} {"id": "PMID:179339", "title": "The spotted nephrogram of renal scleroderma.", "content": "The renal angiographic findings in our two patients with scleroderma and recent onset of hypertension included minor changes in the distal interlobar and arcuate arteries and a nephrogram displaying diffuse, spotty lucencies. Although the spotted nephrogram is occasionally seen in cases of severe nephrosclerosis, we believe that, in the absence of major arterial changes in the arcuate and distal interlobar arteries, it is virtually diagnostic of renal scleroderma.", "contents": "The spotted nephrogram of renal scleroderma. The renal angiographic findings in our two patients with scleroderma and recent onset of hypertension included minor changes in the distal interlobar and arcuate arteries and a nephrogram displaying diffuse, spotty lucencies. Although the spotted nephrogram is occasionally seen in cases of severe nephrosclerosis, we believe that, in the absence of major arterial changes in the arcuate and distal interlobar arteries, it is virtually diagnostic of renal scleroderma."} {"id": "PMID:179340", "title": "The role of emergency excretory urography in evaluation of blunt, abdominal trauma.", "content": "In our hospital, patients seen for blunt, abdominal trauma have an \"emergency\" urogram. The results of our review of 209 such patients with complete urographic evaluations indicate that (1) the clinical examination, urinalysis, and plain abdominal roentgenogram do not reliably allow one to predict which patients would show urographic abnormalities and (2) the clinical management of these patients is rarely altered by the knowledge of the results of the urogram.", "contents": "The role of emergency excretory urography in evaluation of blunt, abdominal trauma. In our hospital, patients seen for blunt, abdominal trauma have an \"emergency\" urogram. The results of our review of 209 such patients with complete urographic evaluations indicate that (1) the clinical examination, urinalysis, and plain abdominal roentgenogram do not reliably allow one to predict which patients would show urographic abnormalities and (2) the clinical management of these patients is rarely altered by the knowledge of the results of the urogram."} {"id": "PMID:179341", "title": "Arthrography in total hip prosthesis complications.", "content": "Previous reports have stressed the value of hip arthrography primarily in determining the presence of loosening of the total hip prosthesis. Although loosening is a common complication and frequently associated with infection, other complications producing a painful hip prosthesis exist and are demonstrable by arthrography. Since the etiologies of these are as diversely different as the treatment, the hip arthrogram is advocated as an integral part of the diagnostic approach to the patient with a painful hip prosthesis in order to assess the specific complication and determine the therapeutic approach.", "contents": "Arthrography in total hip prosthesis complications. Previous reports have stressed the value of hip arthrography primarily in determining the presence of loosening of the total hip prosthesis. Although loosening is a common complication and frequently associated with infection, other complications producing a painful hip prosthesis exist and are demonstrable by arthrography. Since the etiologies of these are as diversely different as the treatment, the hip arthrogram is advocated as an integral part of the diagnostic approach to the patient with a painful hip prosthesis in order to assess the specific complication and determine the therapeutic approach."} {"id": "PMID:179343", "title": "Chiba percutaneous transhepatic cholangiography. A valuable method for visualizing the nondilated biliary tract.", "content": "Percutaneous transhepatic cholangiography with the Chiba needle has had remarkable results in cannulating small bile ducts. We have roentgenographically visualized a nondilated biliary system in the first five out of seven cases attempted. Including our series, there have been 71 successful Chiba studies in 107 nondilated or presumed normal biliary tracts with only one questionable major complication. The technique is simple to learn, particularly in comparison with endoscopic retrograde cholangiography. Since the incidence of complications is low, surgical standby should seldom be necessary. The value of the Chiba percutaneous transhepatic cholangiogram is described via four unusual case reports.", "contents": "Chiba percutaneous transhepatic cholangiography. A valuable method for visualizing the nondilated biliary tract. Percutaneous transhepatic cholangiography with the Chiba needle has had remarkable results in cannulating small bile ducts. We have roentgenographically visualized a nondilated biliary system in the first five out of seven cases attempted. Including our series, there have been 71 successful Chiba studies in 107 nondilated or presumed normal biliary tracts with only one questionable major complication. The technique is simple to learn, particularly in comparison with endoscopic retrograde cholangiography. Since the incidence of complications is low, surgical standby should seldom be necessary. The value of the Chiba percutaneous transhepatic cholangiogram is described via four unusual case reports."} {"id": "PMID:179345", "title": "Computerized tomography (CT) in acute head trauma.", "content": "The retrospective evaluation of 100 cases of head trauma that were subjected to computerized tomography (CT) leads to the following conclusions: (1) Computerized tomography and plain skull survey, should be the first neuroradiological procedures to perform. (2) Angiography may be carried out after computerized tomography when necessary, but as proved by this series, it will be needed in a relatively small number of cases. These include patients with technically limited CT scans or those in whom the possibility of an associated vascular lesion of the cervical or intracranial vessel is clinically suspected. (3) It is essential to obtain CT scans of the best possible quality. Sedation will be required in many instances, but this is considered worth doing because a normal CT scan, without significant technical limitations, will exclude the presence of lesions requiring prompt surgical intervention. Those patients who require surgery will need general anesthesia under any circumstances. (4) There is generally a direct relationship between the severity of clinical presentation and the CT demonstration of the abnormality responsible for the clinical status. Seventy percent of the patients clinically diagnosed as contusion had positive CT scans, and for all practical purposes, 100 percent of patients having trauma more severe than our Group III (contusion) had abnormal CT scans. Likewise, the number and intensity of tissue abnormalities on CT scans increase proportionately with the severity of the clinical signs and symptons. (5) It is foreseen that, with the advent of faster computerized tomographic scanners, the usefulness of this method will increase further, owing to a reduction in the total examination time and the lessened requirement for sedation.", "contents": "Computerized tomography (CT) in acute head trauma. The retrospective evaluation of 100 cases of head trauma that were subjected to computerized tomography (CT) leads to the following conclusions: (1) Computerized tomography and plain skull survey, should be the first neuroradiological procedures to perform. (2) Angiography may be carried out after computerized tomography when necessary, but as proved by this series, it will be needed in a relatively small number of cases. These include patients with technically limited CT scans or those in whom the possibility of an associated vascular lesion of the cervical or intracranial vessel is clinically suspected. (3) It is essential to obtain CT scans of the best possible quality. Sedation will be required in many instances, but this is considered worth doing because a normal CT scan, without significant technical limitations, will exclude the presence of lesions requiring prompt surgical intervention. Those patients who require surgery will need general anesthesia under any circumstances. (4) There is generally a direct relationship between the severity of clinical presentation and the CT demonstration of the abnormality responsible for the clinical status. Seventy percent of the patients clinically diagnosed as contusion had positive CT scans, and for all practical purposes, 100 percent of patients having trauma more severe than our Group III (contusion) had abnormal CT scans. Likewise, the number and intensity of tissue abnormalities on CT scans increase proportionately with the severity of the clinical signs and symptons. (5) It is foreseen that, with the advent of faster computerized tomographic scanners, the usefulness of this method will increase further, owing to a reduction in the total examination time and the lessened requirement for sedation."} {"id": "PMID:179346", "title": "Individualized computer tomography of the skull with the EMI scanner using the 160 X 160 matrix.", "content": "The individualized approach to the performance of computerized tomography of the skull is described. With the use of the 160X160 matrix it is possible to look at the initial scans almost immediately after their completion. If necessary, unsatisfactory scans can be repeated, the position of the head can be changed and artifacts due to motion can be minimized or eliminated. Lesions can be revealed or enhanced with intravenously injected contrast material if desired. The individualized approach has eliminated the need to recall patients and has improved the diagnostic capability of the method.", "contents": "Individualized computer tomography of the skull with the EMI scanner using the 160 X 160 matrix. The individualized approach to the performance of computerized tomography of the skull is described. With the use of the 160X160 matrix it is possible to look at the initial scans almost immediately after their completion. If necessary, unsatisfactory scans can be repeated, the position of the head can be changed and artifacts due to motion can be minimized or eliminated. Lesions can be revealed or enhanced with intravenously injected contrast material if desired. The individualized approach has eliminated the need to recall patients and has improved the diagnostic capability of the method."} {"id": "PMID:179347", "title": "Computed tomography of the normal and infarcted myocardium.", "content": "After intravenous administration of contrast agent, in vitro cardiac scanning showed a significant difference between the attenuation coefficients of the intracavitary blood pool and the myocardial wall, permitting clear delineation of the ventricular cavity. A substantial alteration in hematocrit permitted similar visualization of the intracavitary blood pool-myocardial wall interface. The attenuation coefficient of infarcted myocardium differed sufficiently from that of normal myocardium to render computed tomographic distinction feasible. In three hour old infarctions, the differences between normal and ischemic or infarcted tissue were enhanced by prior administration of contrast agent. These differences in attenuation coefficient indicate that a properly gated CT scanner could be utilized as a noninvasive approach to evaluating suspected or known myocardial infarction and other aspects of cardiac structure and function both in man and in experimental animals.", "contents": "Computed tomography of the normal and infarcted myocardium. After intravenous administration of contrast agent, in vitro cardiac scanning showed a significant difference between the attenuation coefficients of the intracavitary blood pool and the myocardial wall, permitting clear delineation of the ventricular cavity. A substantial alteration in hematocrit permitted similar visualization of the intracavitary blood pool-myocardial wall interface. The attenuation coefficient of infarcted myocardium differed sufficiently from that of normal myocardium to render computed tomographic distinction feasible. In three hour old infarctions, the differences between normal and ischemic or infarcted tissue were enhanced by prior administration of contrast agent. These differences in attenuation coefficient indicate that a properly gated CT scanner could be utilized as a noninvasive approach to evaluating suspected or known myocardial infarction and other aspects of cardiac structure and function both in man and in experimental animals."} {"id": "PMID:179348", "title": "The value of repeat cerebral arteriography in the evaluation of trauma.", "content": "In most patients with head or neck trauma, a single angiogram is sufficient to guide therapy. For those who improve slowly or not at all, however, this is not an adequate basis for diagnosis. Angiography should be repeated after an interval of time to exclude development of a surgically correctable lesion, such as pseudoaneurysm or intracerebral or extracerebral fluid collection.", "contents": "The value of repeat cerebral arteriography in the evaluation of trauma. In most patients with head or neck trauma, a single angiogram is sufficient to guide therapy. For those who improve slowly or not at all, however, this is not an adequate basis for diagnosis. Angiography should be repeated after an interval of time to exclude development of a surgically correctable lesion, such as pseudoaneurysm or intracerebral or extracerebral fluid collection."} {"id": "PMID:179349", "title": "Caudal dislocation of the pons in the adult Arnold-Chiari malformation: an angiographic evaluation.", "content": "The position of the pons, determined angiographically, can be related to the clivus and sella. In adult patients with the Chiari malformation, a caudal dislocation of the pons is frequently associated with the well known anomalously low position of the cerebellar tonsils. This finding may aid in the angiographic diagnosis of the Chiari malformation.", "contents": "Caudal dislocation of the pons in the adult Arnold-Chiari malformation: an angiographic evaluation. The position of the pons, determined angiographically, can be related to the clivus and sella. In adult patients with the Chiari malformation, a caudal dislocation of the pons is frequently associated with the well known anomalously low position of the cerebellar tonsils. This finding may aid in the angiographic diagnosis of the Chiari malformation."} {"id": "PMID:179350", "title": "Angiographic manifestations of bilateral Wilms' tumor.", "content": "Two cases of bilateral Wilms' tumor are presented with discussion of angiographic features. Emphasis is placed on selective angiography in addition to inferior vena cavography for complete evaluation. Because of the incidence of bilateral disease, and the highly vascular nature of the tumor, selective angiography of the contralateral side should be considered in the initial evaluation of unilateral Wilms'tumor. Evaluation of the interface between tumor and normal parenchyma is extremely important in bilateral disease, in anticipation of partial nephrectomy.", "contents": "Angiographic manifestations of bilateral Wilms' tumor. Two cases of bilateral Wilms' tumor are presented with discussion of angiographic features. Emphasis is placed on selective angiography in addition to inferior vena cavography for complete evaluation. Because of the incidence of bilateral disease, and the highly vascular nature of the tumor, selective angiography of the contralateral side should be considered in the initial evaluation of unilateral Wilms'tumor. Evaluation of the interface between tumor and normal parenchyma is extremely important in bilateral disease, in anticipation of partial nephrectomy."} {"id": "PMID:179351", "title": "The abdominal angiographic spectrum of tuberous sclerosis.", "content": "Tuberous sclerosis can present with a variety of clinical, roentgenographic and pathological manifestations. Although we are not advocating abdominal angiography in every patient with tuberous sclerosis, the clinical diagnosis may be difficult in certain cases, particularly in the young patient, and abdominal visceral angiography may lead to the correct diagnosis. In two of our patients, infants ten months of age, the diagnosis of tuberous sclerosis was not made until abdominal angiography had been performed. The most common changes are seen in the kidney where angiographic demonstration of hamartomas, arterial aneurysms, and multiple small cysts in the renal parenchyma are noted. Renal microcysts have not been previously described angiographically although they have been noted in pathological specimens and represent an important feature of the disorder spectrum. In addition, vascular hamartomatous lesions may be demonstrated angiographically in other abdominal organs such as the adrenal gland and liver.", "contents": "The abdominal angiographic spectrum of tuberous sclerosis. Tuberous sclerosis can present with a variety of clinical, roentgenographic and pathological manifestations. Although we are not advocating abdominal angiography in every patient with tuberous sclerosis, the clinical diagnosis may be difficult in certain cases, particularly in the young patient, and abdominal visceral angiography may lead to the correct diagnosis. In two of our patients, infants ten months of age, the diagnosis of tuberous sclerosis was not made until abdominal angiography had been performed. The most common changes are seen in the kidney where angiographic demonstration of hamartomas, arterial aneurysms, and multiple small cysts in the renal parenchyma are noted. Renal microcysts have not been previously described angiographically although they have been noted in pathological specimens and represent an important feature of the disorder spectrum. In addition, vascular hamartomatous lesions may be demonstrated angiographically in other abdominal organs such as the adrenal gland and liver."} {"id": "PMID:179352", "title": "The complication rate of catheter angiography by direct puncture through aorto-femoral bypass grafts.", "content": "A search of the literature revealed no documentation of the complication rate associated with percutaneous catheterization of aorto-femoral bypass grafts in the arteriographic evaluation of graft patency. The authors compared the complication rates of 29 consecutive arteriograms performed through grafts (Group I) with 40 arteriograms performed on non patients (Group II). Neither group had any significant complications, indicating the safety of percutaneous catheterization of the graft site.", "contents": "The complication rate of catheter angiography by direct puncture through aorto-femoral bypass grafts. A search of the literature revealed no documentation of the complication rate associated with percutaneous catheterization of aorto-femoral bypass grafts in the arteriographic evaluation of graft patency. The authors compared the complication rates of 29 consecutive arteriograms performed through grafts (Group I) with 40 arteriograms performed on non patients (Group II). Neither group had any significant complications, indicating the safety of percutaneous catheterization of the graft site."} {"id": "PMID:179353", "title": "Systemic arterial supply to normal basilar segments of the left lower lobe.", "content": "Two cases of sole arterial supply to normal basilar segments of the left lower lobe via an aberrant systemic vessel are described. A spectrum of congenital pulmonary abnormalities with systemic arterial supply to the lung is presented. Complete roentgenologic evaluation is necessary prior to definitive surgery.", "contents": "Systemic arterial supply to normal basilar segments of the left lower lobe. Two cases of sole arterial supply to normal basilar segments of the left lower lobe via an aberrant systemic vessel are described. A spectrum of congenital pulmonary abnormalities with systemic arterial supply to the lung is presented. Complete roentgenologic evaluation is necessary prior to definitive surgery."} {"id": "PMID:179354", "title": "Iatrogenic embolization of the superior mesenteric artery: arteriographic observations and clinical implications.", "content": "Following sudden occlusion of the superior mesenteric artery, there is a characteristic and predictable pattern of blood flow through the instantaneously activated collateral channels. On the left, the first patent jejunal or ileal branch utilizes the central tier of the mesenteric arcades to revascularize the distal trunk of the occluded superior mesenteric artery. On the right, the anastomotic connection between the middle colic, right colic, and ileocolic arteries provides an efficient collateral pathway. These two collateral channels supplement each other and the distal trunk of the occluded superior mesenteric artery is usually rapidly reconstituted. Superior mesenteric artery embolization is frequently an asymptomatic event. There appears to be a variable tolerance of cardiac and non-cardiac patients to the effect of superior mesenteric embolization. Non-cardiac patients may tolerate embolization of the superior mesenteric artery quite well. Cardiac patients frequently respond with an ischemic crisis. The site of embolization is another determining factor. An embolus below the origin of the middle colic artery provides an incomparably more favorable hemodynamic situation than an embolus proximal to the origin of this vessel. The excellent tolerance of our group of patients to superior mesenteric embolization appears to be closely related to these two main factors.", "contents": "Iatrogenic embolization of the superior mesenteric artery: arteriographic observations and clinical implications. Following sudden occlusion of the superior mesenteric artery, there is a characteristic and predictable pattern of blood flow through the instantaneously activated collateral channels. On the left, the first patent jejunal or ileal branch utilizes the central tier of the mesenteric arcades to revascularize the distal trunk of the occluded superior mesenteric artery. On the right, the anastomotic connection between the middle colic, right colic, and ileocolic arteries provides an efficient collateral pathway. These two collateral channels supplement each other and the distal trunk of the occluded superior mesenteric artery is usually rapidly reconstituted. Superior mesenteric artery embolization is frequently an asymptomatic event. There appears to be a variable tolerance of cardiac and non-cardiac patients to the effect of superior mesenteric embolization. Non-cardiac patients may tolerate embolization of the superior mesenteric artery quite well. Cardiac patients frequently respond with an ischemic crisis. The site of embolization is another determining factor. An embolus below the origin of the middle colic artery provides an incomparably more favorable hemodynamic situation than an embolus proximal to the origin of this vessel. The excellent tolerance of our group of patients to superior mesenteric embolization appears to be closely related to these two main factors."} {"id": "PMID:179356", "title": "Radionclide imaging in skeletal inflammatory and ischemic disease in children.", "content": "Sixty-five children were evaluated for presence of skeletal inflammatory and ischemic disease with bone scans and roentgenograms. Several characteristic scintigraphic patterns were observed. Bone scans were significantly more sensitive than roentgenograms in early diagnosis of osteomyelitis and its differentiation from cellulitis, septic arthritis, and bone infarction. The child presenting with possible inflammatory bone disease now is benefited by this important refinement in diagnosis. Faced with the difficult dilemma of choosing appropriate therapy in these frustratingly similar problems, the physician can integrate the clinical findings with nuclear imaging to arrive at early appropriate diagnosis and management.", "contents": "Radionclide imaging in skeletal inflammatory and ischemic disease in children. Sixty-five children were evaluated for presence of skeletal inflammatory and ischemic disease with bone scans and roentgenograms. Several characteristic scintigraphic patterns were observed. Bone scans were significantly more sensitive than roentgenograms in early diagnosis of osteomyelitis and its differentiation from cellulitis, septic arthritis, and bone infarction. The child presenting with possible inflammatory bone disease now is benefited by this important refinement in diagnosis. Faced with the difficult dilemma of choosing appropriate therapy in these frustratingly similar problems, the physician can integrate the clinical findings with nuclear imaging to arrive at early appropriate diagnosis and management."} {"id": "PMID:179357", "title": "\"Doughnut\" sign in brain scanning.", "content": "The significance of the \"doughnut\" sign at present is relegated to characterizing the morphology of a lesion. The use of the \"doughnut\" sign in differential diagnosis should not be attempted except in specific clinical contexts, and never excluding other evidence. The \"doughnut\" sign in scanning together with other studies such as angiography and computerized axial tomography gives additional characterizing data in the neuroradiologic evaluation of a patient.", "contents": "\"Doughnut\" sign in brain scanning. The significance of the \"doughnut\" sign at present is relegated to characterizing the morphology of a lesion. The use of the \"doughnut\" sign in differential diagnosis should not be attempted except in specific clinical contexts, and never excluding other evidence. The \"doughnut\" sign in scanning together with other studies such as angiography and computerized axial tomography gives additional characterizing data in the neuroradiologic evaluation of a patient."} {"id": "PMID:179358", "title": "Ultrasonic evaluation of the unilateral nonvisualized kidney.", "content": "There are several techniques for evaluating the nonvisualized kidney. Nephrotomography may be helpful in those patients who have some remaining renal function. Radionuclide renal flow and imaging studies are more sensitive than nephrotomography in detecting hydronephrosis, the most common cause of unilateral renal nonvisualization, but also require some renal function to be of diagnostic value. Diagnostic ultrasound, since it is independent of renal function, is an even more sinsitive indicator of urinary obstruction, detecting those cases where no functioning renal parenchyma is present. This non-invasive technique can accurately guide percutaneous puncture of the collecting system, permitting antegrade localization of the obstructing lesion. When ultrasonography demonstrates a solid mass in the renal fossa, angiography is recommended for definitive diagnosis. When no kidney is identified renal venography may be useful in differentiating between a small nonfunctioning kidney and renal agenesis.", "contents": "Ultrasonic evaluation of the unilateral nonvisualized kidney. There are several techniques for evaluating the nonvisualized kidney. Nephrotomography may be helpful in those patients who have some remaining renal function. Radionuclide renal flow and imaging studies are more sensitive than nephrotomography in detecting hydronephrosis, the most common cause of unilateral renal nonvisualization, but also require some renal function to be of diagnostic value. Diagnostic ultrasound, since it is independent of renal function, is an even more sinsitive indicator of urinary obstruction, detecting those cases where no functioning renal parenchyma is present. This non-invasive technique can accurately guide percutaneous puncture of the collecting system, permitting antegrade localization of the obstructing lesion. When ultrasonography demonstrates a solid mass in the renal fossa, angiography is recommended for definitive diagnosis. When no kidney is identified renal venography may be useful in differentiating between a small nonfunctioning kidney and renal agenesis."} {"id": "PMID:179359", "title": "Factors that modify the radio-response of cancer of the nasopharynx.", "content": "A study of 152 cases of carcinoma of the nasopharynx was carried out for evaluation of various features of the tumors. Survival is greatest in middle aged patients and poorest in patients under 20 years of age. Patients who presented with lymph node involvement had a better survival rate than those without, and those with undifferentiated tumors survived longer, although tumors in this group metastasized earlier. Those tumors which arose on the postero-superior wall of the nasopharynx were associated with a lower cure rate than those situated elsewhere. Spread to adjacent tissues diminished the cure rate, but the rate fell particularly low if there was spread to bone or to the central nervous system. If no neck lymph nodes were involved, patients with undifferentiated and well-differentiated lesions fared equally well, but if there was involvement of the neck lymph nodes, those with undifferentiated primary lesions obtained a better cure rate. The influence of the type of local spread, the presence of distant metastasis, and survival in relation to the histological and clinical grading of the tumor were also evaluated.", "contents": "Factors that modify the radio-response of cancer of the nasopharynx. A study of 152 cases of carcinoma of the nasopharynx was carried out for evaluation of various features of the tumors. Survival is greatest in middle aged patients and poorest in patients under 20 years of age. Patients who presented with lymph node involvement had a better survival rate than those without, and those with undifferentiated tumors survived longer, although tumors in this group metastasized earlier. Those tumors which arose on the postero-superior wall of the nasopharynx were associated with a lower cure rate than those situated elsewhere. Spread to adjacent tissues diminished the cure rate, but the rate fell particularly low if there was spread to bone or to the central nervous system. If no neck lymph nodes were involved, patients with undifferentiated and well-differentiated lesions fared equally well, but if there was involvement of the neck lymph nodes, those with undifferentiated primary lesions obtained a better cure rate. The influence of the type of local spread, the presence of distant metastasis, and survival in relation to the histological and clinical grading of the tumor were also evaluated."} {"id": "PMID:179360", "title": "Definitive treatment of carcinoma of the rectum by intracavitary radiation therapy.", "content": "A combination of external and contact irradiation treatment has been used successfully in treatment of selected patients with carcinoma of the rectum. The advantages include eliminating a permanent colostomy. If the treatment is unsuccessful in controlling the lesion, electrocoagulation and abdominoperineal resection are still available.", "contents": "Definitive treatment of carcinoma of the rectum by intracavitary radiation therapy. A combination of external and contact irradiation treatment has been used successfully in treatment of selected patients with carcinoma of the rectum. The advantages include eliminating a permanent colostomy. If the treatment is unsuccessful in controlling the lesion, electrocoagulation and abdominoperineal resection are still available."} {"id": "PMID:179361", "title": "Serial studies of immunocompetence in head and neck cancer patients undergoing radiation therapy.", "content": "Studies of the immunocompetence of patients undergoing radiation therapy were carried out before and after treatment. The immunological evaluation is a valuable prognostic tool for patients with squamous cell carcinomas of the head and neck. The degree of immunoresponsiveness is not related to the stage of the primary tumor, but it definitely correlates with the extent of lymph node involvemnt. This evaluation may permit identification of those cases for which immunotherapy is indicated.", "contents": "Serial studies of immunocompetence in head and neck cancer patients undergoing radiation therapy. Studies of the immunocompetence of patients undergoing radiation therapy were carried out before and after treatment. The immunological evaluation is a valuable prognostic tool for patients with squamous cell carcinomas of the head and neck. The degree of immunoresponsiveness is not related to the stage of the primary tumor, but it definitely correlates with the extent of lymph node involvemnt. This evaluation may permit identification of those cases for which immunotherapy is indicated."} {"id": "PMID:179362", "title": "Hemangiopericytoma: report of three cases regarding role of radiation therapy.", "content": "The experience in treating three patients with hemangiopericytoma is reviewed. One patient was given irradiation alone, and the others were both treated with surgery and irradiation. Our experience reinforces reports of the usefulness of irradiation in treating this neoplasm and its metastases.", "contents": "Hemangiopericytoma: report of three cases regarding role of radiation therapy. The experience in treating three patients with hemangiopericytoma is reviewed. One patient was given irradiation alone, and the others were both treated with surgery and irradiation. Our experience reinforces reports of the usefulness of irradiation in treating this neoplasm and its metastases."} {"id": "PMID:179363", "title": "Congenital absence of the ductus venosus: with direct connection between the umbilical vein and the distal inferior vena cava.", "content": "Umbilical vessel catheterization in a neonate with Noonan's syndrome disclosed a unique developmental anomaly of the umbilical vein. There was no evidence of a ductus venosus nor any connection between the vein and the portal hepatic venous system. The umbilical vein instead entered the inferior vena cava directly at the level of the iliac veins. There was a single umbilical artery.", "contents": "Congenital absence of the ductus venosus: with direct connection between the umbilical vein and the distal inferior vena cava. Umbilical vessel catheterization in a neonate with Noonan's syndrome disclosed a unique developmental anomaly of the umbilical vein. There was no evidence of a ductus venosus nor any connection between the vein and the portal hepatic venous system. The umbilical vein instead entered the inferior vena cava directly at the level of the iliac veins. There was a single umbilical artery."} {"id": "PMID:179364", "title": "Aneurysmal bone cyst of the orbit with unusual angiographic features.", "content": "A 14 month old boy with sudden onset of proptosis of the left eye due to an aneurysmal bone cyst of the orbit is reported. Sequential plain films of the orbital region demonstrated changes ranging from subtle loss of bone definition of the orbital margin to the characteristic appearance of an aneurysmal bone cyst twelve months later. Arteriography at the time of the initial evaluation demonstrated prolonged retention of the contrast medium which we believe represents changes secondary to the number of giant cells present in the tumor rather than the relative vascularity of the lesion. While aneurysmal bone cyst of the orbit is extremely rare, it should be included in the differential diagnosis of proptosis in the pediatric age group.", "contents": "Aneurysmal bone cyst of the orbit with unusual angiographic features. A 14 month old boy with sudden onset of proptosis of the left eye due to an aneurysmal bone cyst of the orbit is reported. Sequential plain films of the orbital region demonstrated changes ranging from subtle loss of bone definition of the orbital margin to the characteristic appearance of an aneurysmal bone cyst twelve months later. Arteriography at the time of the initial evaluation demonstrated prolonged retention of the contrast medium which we believe represents changes secondary to the number of giant cells present in the tumor rather than the relative vascularity of the lesion. While aneurysmal bone cyst of the orbit is extremely rare, it should be included in the differential diagnosis of proptosis in the pediatric age group."} {"id": "PMID:179366", "title": "Extra-abdominal desmoid of the axillary tail mimicking breast carcinoma.", "content": "A case is reported of an extra-abdominal desmoid tumor presenting as an axillary tail breast mass. This represents the third reported case and the first description of the roentgenographic findings of this entity. That this tumor can be confused with carcinoma of the breast is emphasized.", "contents": "Extra-abdominal desmoid of the axillary tail mimicking breast carcinoma. A case is reported of an extra-abdominal desmoid tumor presenting as an axillary tail breast mass. This represents the third reported case and the first description of the roentgenographic findings of this entity. That this tumor can be confused with carcinoma of the breast is emphasized."} {"id": "PMID:179368", "title": "New frontier for radiology: computed tomography. 40th Annual Preston M. Hickey Memorial Lecture.", "content": "The basic principles of computed tomography (CT) and their application are discussed. The impact of this method on neuroradiologic diagnosis is reviewed, including economic considerations and the effect on nuclear medicine and other diagnostic procedures. The initial experiences of the Mallinckrodt Institute with whole body scanning are illustrated, and failure possibilities for CT are predicted.", "contents": "New frontier for radiology: computed tomography. 40th Annual Preston M. Hickey Memorial Lecture. The basic principles of computed tomography (CT) and their application are discussed. The impact of this method on neuroradiologic diagnosis is reviewed, including economic considerations and the effect on nuclear medicine and other diagnostic procedures. The initial experiences of the Mallinckrodt Institute with whole body scanning are illustrated, and failure possibilities for CT are predicted."} {"id": "PMID:179369", "title": "Breast patterns as an index of risk for developing breast cancer.", "content": "The radiographic appearance of the breast parenchyma provides a method of predicting who will develop a breast cancer. This paper describes a restrospective study of 7,214 patients. On the basis of the radiographic appearance of the breast parenchyma, patients were placed into one of four groups of risk for developing carcinoma of the breast. Follow-up studies revealed a stepwise progression in the incidence of developing carcinoma of the breast at least 6 months after the radiographic examination. In one of the two substudies, there was a 37 times greater incidence for those at highest risk compared to the low risk group. The classifications presented are thought to be of value in the everyday practice of mammography as well as in planning screening programs.", "contents": "Breast patterns as an index of risk for developing breast cancer. The radiographic appearance of the breast parenchyma provides a method of predicting who will develop a breast cancer. This paper describes a restrospective study of 7,214 patients. On the basis of the radiographic appearance of the breast parenchyma, patients were placed into one of four groups of risk for developing carcinoma of the breast. Follow-up studies revealed a stepwise progression in the incidence of developing carcinoma of the breast at least 6 months after the radiographic examination. In one of the two substudies, there was a 37 times greater incidence for those at highest risk compared to the low risk group. The classifications presented are thought to be of value in the everyday practice of mammography as well as in planning screening programs."} {"id": "PMID:179370", "title": "Radiographic visualization of left ventricular aneurysms on lateral chest film.", "content": "The diagnosis of left ventricular aneurysm on routine chest examination can be elusive. Six cases are presented which illustrate a radiographic sign not previously emphasized: a soft tissue border seen retrosternally or superiorly on lateral chest film produced by the wall of the aneurysm silhouetting against the midline cardiac shadow. This sign is not always present since it is dependent on the direction of projection of the aneurysm. However, when observed, it should suggest the proper diagnosis.", "contents": "Radiographic visualization of left ventricular aneurysms on lateral chest film. The diagnosis of left ventricular aneurysm on routine chest examination can be elusive. Six cases are presented which illustrate a radiographic sign not previously emphasized: a soft tissue border seen retrosternally or superiorly on lateral chest film produced by the wall of the aneurysm silhouetting against the midline cardiac shadow. This sign is not always present since it is dependent on the direction of projection of the aneurysm. However, when observed, it should suggest the proper diagnosis."} {"id": "PMID:179371", "title": "The chest x-ray in acute left ventricular power failure: an aid to determining prognosis of patients supported by intraaortic balloon pumping.", "content": "Serial chest x-rays were used as a means of evaluating the hemodynamic status of 43 patients in acute left ventricular power failure (LVPF) complicating acute myocardial infarction who were assisted with balloon pumping. The following findings were reported: 1. In patients with acute myocardial infarction, prediction of the hemodynamic status on the basis of chest x-rays is less reliable when severe LVPF is present as a complication. 2. The incidence and severity of roentgenographic findings of congestive heart failure and pulmonary edema are increased in patients with severe LVPF compared to patients with uncomplicated myocardial infarction. 3. Improvement in the roentgenographic degree of heart failure with positive clinical and hemodynamic responses to 24 hr or less of balloon pumping is an indication that patients in severe acute LVPF may survive. Patients with deteriorating or unchanging chest x-ray findings have an extremely poor prognosis. These patients should be evaluated by cardiac catheterization and coronary arteriography to determine the appropriateness of emergency surgical correction.", "contents": "The chest x-ray in acute left ventricular power failure: an aid to determining prognosis of patients supported by intraaortic balloon pumping. Serial chest x-rays were used as a means of evaluating the hemodynamic status of 43 patients in acute left ventricular power failure (LVPF) complicating acute myocardial infarction who were assisted with balloon pumping. The following findings were reported: 1. In patients with acute myocardial infarction, prediction of the hemodynamic status on the basis of chest x-rays is less reliable when severe LVPF is present as a complication. 2. The incidence and severity of roentgenographic findings of congestive heart failure and pulmonary edema are increased in patients with severe LVPF compared to patients with uncomplicated myocardial infarction. 3. Improvement in the roentgenographic degree of heart failure with positive clinical and hemodynamic responses to 24 hr or less of balloon pumping is an indication that patients in severe acute LVPF may survive. Patients with deteriorating or unchanging chest x-ray findings have an extremely poor prognosis. These patients should be evaluated by cardiac catheterization and coronary arteriography to determine the appropriateness of emergency surgical correction."} {"id": "PMID:179372", "title": "Abnormal left ventricular catheter motion: an ancillary angiographic sign of left atrial myxoma.", "content": "The normal motion of a left ventricular catheter parallels that of the aortic root; it moves anterior during systole and posterior during diastole. In contrast, a prolapsing left atrial myxoma causes paradoxical motion of the catheter; posterior during systole and anterior during diastole. Paradoxical motion was found in each of five cases of prolapsing left atrial myxoma (no false negatives), and in six out of 61 controls (six false positives). In the false positive cases, the catheter was not positioned on the ventricular floor and usually only minor degrees of abnormal motion were present. Paradoxical motion of the left ventricular catheter is an ancillary angiographic finding in prolapsing left atrial tumor.", "contents": "Abnormal left ventricular catheter motion: an ancillary angiographic sign of left atrial myxoma. The normal motion of a left ventricular catheter parallels that of the aortic root; it moves anterior during systole and posterior during diastole. In contrast, a prolapsing left atrial myxoma causes paradoxical motion of the catheter; posterior during systole and anterior during diastole. Paradoxical motion was found in each of five cases of prolapsing left atrial myxoma (no false negatives), and in six out of 61 controls (six false positives). In the false positive cases, the catheter was not positioned on the ventricular floor and usually only minor degrees of abnormal motion were present. Paradoxical motion of the left ventricular catheter is an ancillary angiographic finding in prolapsing left atrial tumor."} {"id": "PMID:179373", "title": "Evaluation of routine double contrast views of the anterior wall of the stomach.", "content": "Since June 1974, we have performed over 1,500 consecutive double contrast upper gastrointestinal examinations. The double contrast study of the anterior wall has been a useful adjunct to conventional mucosal relief and dosed compression studies. Nevertheless, the low diagnostic yield of the anterior wall examination does not appear to justify including it as part of the routine double contrast upper gastrointestinal study.", "contents": "Evaluation of routine double contrast views of the anterior wall of the stomach. Since June 1974, we have performed over 1,500 consecutive double contrast upper gastrointestinal examinations. The double contrast study of the anterior wall has been a useful adjunct to conventional mucosal relief and dosed compression studies. Nevertheless, the low diagnostic yield of the anterior wall examination does not appear to justify including it as part of the routine double contrast upper gastrointestinal study."} {"id": "PMID:179374", "title": "Intussusception of the appendix in children.", "content": "Intussusception of the appendix is uncommon and an unusual cause of ileocolic intussusception. The pediatric age group is most often affected. Appendiceal intussusception may present as primary appendiceal invagination but more commonly leads to secondary intussusception. Two cases of partial appendiceal intussusception leading to secondary intussusception are presented. Classification, symptomatology, radiographic appearance, and differential diagnosis are discussed.", "contents": "Intussusception of the appendix in children. Intussusception of the appendix is uncommon and an unusual cause of ileocolic intussusception. The pediatric age group is most often affected. Appendiceal intussusception may present as primary appendiceal invagination but more commonly leads to secondary intussusception. Two cases of partial appendiceal intussusception leading to secondary intussusception are presented. Classification, symptomatology, radiographic appearance, and differential diagnosis are discussed."} {"id": "PMID:179375", "title": "Plain film findings of gastric volvulus herniating into the chest.", "content": "When confronted with a chest radiograph demonstrating two large air-fluid levels, one in the retrocardiac mediastinum and the other beneath the left hemidiaphragm, the possibility of gastric volvulus herniating into the thorax should be strongly considered. These patients should have an immediate contrast study for further evaluation.", "contents": "Plain film findings of gastric volvulus herniating into the chest. When confronted with a chest radiograph demonstrating two large air-fluid levels, one in the retrocardiac mediastinum and the other beneath the left hemidiaphragm, the possibility of gastric volvulus herniating into the thorax should be strongly considered. These patients should have an immediate contrast study for further evaluation."} {"id": "PMID:179376", "title": "Chondrosarcoma of the esophagus.", "content": "A 46-year-old man had a large noncalcified tumor in the wall of the thoracic esophagus narrowing its lumen by projection of numerous firm nodular masses. The pathologic diagnosis was chondrosarcoma. Malignant degeneration of a tracheobronchial cartilaginous remnant is the main consideration in this first recorded case of esophageal chondrosarcoma.", "contents": "Chondrosarcoma of the esophagus. A 46-year-old man had a large noncalcified tumor in the wall of the thoracic esophagus narrowing its lumen by projection of numerous firm nodular masses. The pathologic diagnosis was chondrosarcoma. Malignant degeneration of a tracheobronchial cartilaginous remnant is the main consideration in this first recorded case of esophageal chondrosarcoma."} {"id": "PMID:179377", "title": "Localized giant pseudopolyposis in ulcerative colitis.", "content": "A case of localized giant pseudopolyposis in ulcertative colitis is discussed in which a mass effect mimicked tumor. The fulminant collection of pseudopolyps was palable in the epigastrium on physical exam and caused a partial obstruction to the retrograde flow of barium. Carcinoma is a worrisome possibility in ulcerative colitis, but localized giant pseudopolyposis may also present as a mass.", "contents": "Localized giant pseudopolyposis in ulcerative colitis. A case of localized giant pseudopolyposis in ulcertative colitis is discussed in which a mass effect mimicked tumor. The fulminant collection of pseudopolyps was palable in the epigastrium on physical exam and caused a partial obstruction to the retrograde flow of barium. Carcinoma is a worrisome possibility in ulcerative colitis, but localized giant pseudopolyposis may also present as a mass."} {"id": "PMID:179378", "title": "Clinical and radiographic \"reankylosis\" following hip surgery in ankylosing spondylitis.", "content": "Eleven patients with ankylosing spondylitis underwent reconstructive hip surgery (21 hips). In 10 of these hips multiple surgical procedures had been performed. The final procedure included total hip arthroplasties (16 hips), femoral cup arthroplasties (four hips) and an Austin-Moore prosthetic replacement (one hip). A clinical and radiographic evaluation in the postoperative period revealed a high incidence of decreased joint motion and heterotopic ossification. Clinically moderate to severe restriction of motion was noted in 12 hips, and in six of these \"reankylosis\" was present. Radiographically moderate to severe new bone formation was seen in 11 hips, and in nine of these \"reankylosis\" was suggested. An association of excessive ossification and multiple surgical procedures was evident. It would appear that when the prime indication for hip surgery in patients with ankylosing spondylitis is restricted motion, the operation may not be beneficial.", "contents": "Clinical and radiographic \"reankylosis\" following hip surgery in ankylosing spondylitis. Eleven patients with ankylosing spondylitis underwent reconstructive hip surgery (21 hips). In 10 of these hips multiple surgical procedures had been performed. The final procedure included total hip arthroplasties (16 hips), femoral cup arthroplasties (four hips) and an Austin-Moore prosthetic replacement (one hip). A clinical and radiographic evaluation in the postoperative period revealed a high incidence of decreased joint motion and heterotopic ossification. Clinically moderate to severe restriction of motion was noted in 12 hips, and in six of these \"reankylosis\" was present. Radiographically moderate to severe new bone formation was seen in 11 hips, and in nine of these \"reankylosis\" was suggested. An association of excessive ossification and multiple surgical procedures was evident. It would appear that when the prime indication for hip surgery in patients with ankylosing spondylitis is restricted motion, the operation may not be beneficial."} {"id": "PMID:179379", "title": "Medial deviation of the upper pole calyx on the intravenous urogram as an indication of vesicoureteral reflex.", "content": "Eighty-three intravenous pyelograms were studied to evaluate thinning of the parenchyma on the medial edge of the superior pole of the kidney as an indicator of vesicoureteral reflux. The data indicate that this finding is suggestive of reflux: the greater the difference between the two sides, the more likely the patient is to reflux.", "contents": "Medial deviation of the upper pole calyx on the intravenous urogram as an indication of vesicoureteral reflex. Eighty-three intravenous pyelograms were studied to evaluate thinning of the parenchyma on the medial edge of the superior pole of the kidney as an indicator of vesicoureteral reflux. The data indicate that this finding is suggestive of reflux: the greater the difference between the two sides, the more likely the patient is to reflux."} {"id": "PMID:179380", "title": "Ultrasound diagnosis of posttransplant renal lymphocele.", "content": "Two cases of posttransplant renal lymphoceles were diagnosed and followed by ultrasound. Lymphocele formation is a significant but often not thought of cause in a rejectionlike picture. Because of its noninvasive nature, ultrasound is an ideal method to detect and follow this complication.", "contents": "Ultrasound diagnosis of posttransplant renal lymphocele. Two cases of posttransplant renal lymphoceles were diagnosed and followed by ultrasound. Lymphocele formation is a significant but often not thought of cause in a rejectionlike picture. Because of its noninvasive nature, ultrasound is an ideal method to detect and follow this complication."} {"id": "PMID:179381", "title": "Pseudotumor of the kidney: a sequel to regional glomerulonephritis.", "content": "An unusual case of chronic renal failure associated with an abnormal intravenous urogram simulating renal neoplasm is discussed. Extensive radiographic and histologic studies support the contention that the observed mass lesion resulted from a segmental or regional compensatory hypertrophy. It is likely that this case represents a variant of unilateral glomerulonephritis with sparing of a segment or lobe of one kidney and subsequent hypertrophy of that segment as the remaining renal mass atrophied.", "contents": "Pseudotumor of the kidney: a sequel to regional glomerulonephritis. An unusual case of chronic renal failure associated with an abnormal intravenous urogram simulating renal neoplasm is discussed. Extensive radiographic and histologic studies support the contention that the observed mass lesion resulted from a segmental or regional compensatory hypertrophy. It is likely that this case represents a variant of unilateral glomerulonephritis with sparing of a segment or lobe of one kidney and subsequent hypertrophy of that segment as the remaining renal mass atrophied."} {"id": "PMID:179382", "title": "Tortuosity of the cavernous carotid arteries causing sellar expansion simulating pituitary adenoma.", "content": "Tortuous, medially-displaced cavernous carotid arteries may cause sellar enlargement which simulates pituitary adenoma. Systemic hypertension appears to account for this tortuosity in some cases, while a congenital anomaly is probably responsible in others. Medical position of the carotid sulci may be demonstrated on sellar tomography. Cerebral arteriography provides the correct diagnosis. Surgery, particularly transsphenoidal hypophysectomy, should be avoided in such patients.", "contents": "Tortuosity of the cavernous carotid arteries causing sellar expansion simulating pituitary adenoma. Tortuous, medially-displaced cavernous carotid arteries may cause sellar enlargement which simulates pituitary adenoma. Systemic hypertension appears to account for this tortuosity in some cases, while a congenital anomaly is probably responsible in others. Medical position of the carotid sulci may be demonstrated on sellar tomography. Cerebral arteriography provides the correct diagnosis. Surgery, particularly transsphenoidal hypophysectomy, should be avoided in such patients."} {"id": "PMID:179383", "title": "Serial cerebral angiography in stereoscopic magnification.", "content": "A ceiling x-ray tube support with synchronous up and down movements is described for obtaining two parallel x-ray beams with a short focal-film distance. Stereoscopic cerebral angiography is performed with direct serial magnification using a heavy-duty anode tube with a 0.1 mm focus. This technique combines the advantages of magnification and stereoscopic angiography. Small arterial and venous changes can be observed clearly in three dimensions. The usefulness and limitations of this method are discussed using clinical and experimental data.", "contents": "Serial cerebral angiography in stereoscopic magnification. A ceiling x-ray tube support with synchronous up and down movements is described for obtaining two parallel x-ray beams with a short focal-film distance. Stereoscopic cerebral angiography is performed with direct serial magnification using a heavy-duty anode tube with a 0.1 mm focus. This technique combines the advantages of magnification and stereoscopic angiography. Small arterial and venous changes can be observed clearly in three dimensions. The usefulness and limitations of this method are discussed using clinical and experimental data."} {"id": "PMID:179384", "title": "Radiologic changes in the thymoma-hypogammaglobulinemia syndrome.", "content": "Radiologic findings in the thymoma-hypogammaglobulinemia syndrome are encountered in three stages reflecting the natural history of the syndrome. Initially, a mediastinal mass is apparent on chest x-ray in an asymptomataic patient. At this stage a failing immune system has apparently induced compensatory thymic hyperplasia which progresses to frank neoplasia. In 55% of the cases this thymic tumor is paracardiac in location. With progressive failure of immunoglobulin production, acute and chronic pulmonary infiltrates occur secondary to infection. Markedly, decreased IgA in the bowel may eventually be manifested by radiologic changes of exudative enteropathy.", "contents": "Radiologic changes in the thymoma-hypogammaglobulinemia syndrome. Radiologic findings in the thymoma-hypogammaglobulinemia syndrome are encountered in three stages reflecting the natural history of the syndrome. Initially, a mediastinal mass is apparent on chest x-ray in an asymptomataic patient. At this stage a failing immune system has apparently induced compensatory thymic hyperplasia which progresses to frank neoplasia. In 55% of the cases this thymic tumor is paracardiac in location. With progressive failure of immunoglobulin production, acute and chronic pulmonary infiltrates occur secondary to infection. Markedly, decreased IgA in the bowel may eventually be manifested by radiologic changes of exudative enteropathy."} {"id": "PMID:179385", "title": "Cerebro-costo-mandibular syndrome: long term follow-up of a patient and review of the literature.", "content": "The cerebro-costo-mandibular syndrome is a rare disorder, and most afflicted infants die during the first few months of life. The pertinent features of the syndrome are reviewed, and a hitherto undescribed finding in the pelvis is described. A case is reported in which vigorous treatment permitted survival. Serial roentgenograms subsequently demonstrated a progressive diminution of the characteristic posterior rib-gap defects.", "contents": "Cerebro-costo-mandibular syndrome: long term follow-up of a patient and review of the literature. The cerebro-costo-mandibular syndrome is a rare disorder, and most afflicted infants die during the first few months of life. The pertinent features of the syndrome are reviewed, and a hitherto undescribed finding in the pelvis is described. A case is reported in which vigorous treatment permitted survival. Serial roentgenograms subsequently demonstrated a progressive diminution of the characteristic posterior rib-gap defects."} {"id": "PMID:179386", "title": "Intestinal perforations secondary to nasojejunal feeding tubes.", "content": "Infant alimentation by nasojejunal tube feeding has been successfully used since 1973. A significant complication is small bowel perforation by the tube; three cases are presented. The differential diagnosis includes spontaneous gastric perforation and necrotizing enterocolitis. Nasojejunal tube perforation almost always occurs in the distal duodenum. It is likely the result of peristaltic activity which propels the tube along the relatively rigid duodenal loop. Thus it is preferable to position the tube end distal to the ligament of Treitz.", "contents": "Intestinal perforations secondary to nasojejunal feeding tubes. Infant alimentation by nasojejunal tube feeding has been successfully used since 1973. A significant complication is small bowel perforation by the tube; three cases are presented. The differential diagnosis includes spontaneous gastric perforation and necrotizing enterocolitis. Nasojejunal tube perforation almost always occurs in the distal duodenum. It is likely the result of peristaltic activity which propels the tube along the relatively rigid duodenal loop. Thus it is preferable to position the tube end distal to the ligament of Treitz."} {"id": "PMID:179387", "title": "Lesion conspicuity, structured noise, and film reader error.", "content": "The concept of conspicuity is introduced in an attempt to objectively quantitate radiographic observational error. Defined as a ratio between lesion contrast and surround complexity, the measure correlates well with the probability of detecting faint nodular lesions in chest radiographs. The concept helps in understanding why abnormalities are missed by radiologists. It is also used to explain why image-processing techniques advocated in the past did not yield improvements in diagnostic accuracy and to outline directions for the future. Preliminary results are presented which show that photographic subtraction can increase the conspicuity of simulated early lung lesions and improve their detection.", "contents": "Lesion conspicuity, structured noise, and film reader error. The concept of conspicuity is introduced in an attempt to objectively quantitate radiographic observational error. Defined as a ratio between lesion contrast and surround complexity, the measure correlates well with the probability of detecting faint nodular lesions in chest radiographs. The concept helps in understanding why abnormalities are missed by radiologists. It is also used to explain why image-processing techniques advocated in the past did not yield improvements in diagnostic accuracy and to outline directions for the future. Preliminary results are presented which show that photographic subtraction can increase the conspicuity of simulated early lung lesions and improve their detection."} {"id": "PMID:179388", "title": "A circular test pattern for evaluating x-ray tube focal spots.", "content": "The design and use of a circular x-ray resolution test pattern is presented. This pattern is shown to yield equivalent focal spot dimensions equal to those obtained with the more commonly used star pattern. The advantage of using the circular pattern is that it obviates the necessity of positioning the pattern strictly along the x-ray beam central axis. A major source of experimental error in making focal spot measurements is therefore circumvented, especially in the case of x-ray tubes with a small target angle.", "contents": "A circular test pattern for evaluating x-ray tube focal spots. The design and use of a circular x-ray resolution test pattern is presented. This pattern is shown to yield equivalent focal spot dimensions equal to those obtained with the more commonly used star pattern. The advantage of using the circular pattern is that it obviates the necessity of positioning the pattern strictly along the x-ray beam central axis. A major source of experimental error in making focal spot measurements is therefore circumvented, especially in the case of x-ray tubes with a small target angle."} {"id": "PMID:179390", "title": "Lack of gallium uptake in primary hepatic amyloidosis.", "content": "99mTc-sulfur colloid and 67Ga citrate hepatic scintigrams showed matching defects in a patient with diffuse primary amyloidosis. Amyloidosis should be added to the usual differential diagnosis of such matching lesions which includes cysts, fibrosis, most benign tumors, and occasional metastatic lesions which do not concentrate gallium.", "contents": "Lack of gallium uptake in primary hepatic amyloidosis. 99mTc-sulfur colloid and 67Ga citrate hepatic scintigrams showed matching defects in a patient with diffuse primary amyloidosis. Amyloidosis should be added to the usual differential diagnosis of such matching lesions which includes cysts, fibrosis, most benign tumors, and occasional metastatic lesions which do not concentrate gallium."} {"id": "PMID:179391", "title": "Incidentally detected thrombosed vein during 67Ga citrate scanning.", "content": "A patient with stage IVA Hodgkin's disease developed thrombosis of the right cephalic vein at the site of an indwelling catheter. A few weeks later, 72 and 96 hr scans after injection of 67Ga citrate revealed an increased linear uptake where the thrombosed vein was palpated. As far as we know, this is the first case showing abnormal uptake of this agent in a thrombosed vein. It is postulated that residual chronic inflammatory cells are responsible for 67Ga citrate uptake in this case.", "contents": "Incidentally detected thrombosed vein during 67Ga citrate scanning. A patient with stage IVA Hodgkin's disease developed thrombosis of the right cephalic vein at the site of an indwelling catheter. A few weeks later, 72 and 96 hr scans after injection of 67Ga citrate revealed an increased linear uptake where the thrombosed vein was palpated. As far as we know, this is the first case showing abnormal uptake of this agent in a thrombosed vein. It is postulated that residual chronic inflammatory cells are responsible for 67Ga citrate uptake in this case."} {"id": "PMID:179392", "title": "Electron beam therapy in head and neck tumors.", "content": "Electron beam therapy with its high energy capabilities appears promising as a therapeutic modality in head and neck neoplasms. Over a 10-year period, 153 cases of head and neck neoplasms involving the alveolar ridge, floor of mouth, buccal mucosa, retromolar trigone, tonsil, parotid, tongue, and pharynx were treated. The pharyngeal group was removed from consideration because of the unsuitability of this lesion for single port therapy. Normal standard doses and time-dose fractions are included as a basis for treatment comparison, and the influence of stage on survival is noted. Survival and tolerance of this form of treatment is comparable to photon therapy and may in fact result in fewer complications.", "contents": "Electron beam therapy in head and neck tumors. Electron beam therapy with its high energy capabilities appears promising as a therapeutic modality in head and neck neoplasms. Over a 10-year period, 153 cases of head and neck neoplasms involving the alveolar ridge, floor of mouth, buccal mucosa, retromolar trigone, tonsil, parotid, tongue, and pharynx were treated. The pharyngeal group was removed from consideration because of the unsuitability of this lesion for single port therapy. Normal standard doses and time-dose fractions are included as a basis for treatment comparison, and the influence of stage on survival is noted. Survival and tolerance of this form of treatment is comparable to photon therapy and may in fact result in fewer complications."} {"id": "PMID:179393", "title": "Surgical treatment of advanced carcinoma of the floor of the mouth.", "content": "The anterior arch of the mandible is essential for satisfactory oral function and appearance. It can be preserved in surgical treatment of advanced cancers of the floor of the mouth by partial thickness resection. Surgery and radiation are approximately equally effective in the control of advanced (T3) primary lesions. A treatment plan is proposed which employs a combination of nondisabling surgical resection followed by immediate postoperative radiation. Of 19 patients with T2, T3, and T4 lesions treated and followed 1 year or more, 11 were free of cancer, including six who had positive lymph nodes. Of those dying of cancer, only one had local recurrence, while recurrence in the neck occurred in four. This report further strengthens the need for postsurgical radiation in certain situations.", "contents": "Surgical treatment of advanced carcinoma of the floor of the mouth. The anterior arch of the mandible is essential for satisfactory oral function and appearance. It can be preserved in surgical treatment of advanced cancers of the floor of the mouth by partial thickness resection. Surgery and radiation are approximately equally effective in the control of advanced (T3) primary lesions. A treatment plan is proposed which employs a combination of nondisabling surgical resection followed by immediate postoperative radiation. Of 19 patients with T2, T3, and T4 lesions treated and followed 1 year or more, 11 were free of cancer, including six who had positive lymph nodes. Of those dying of cancer, only one had local recurrence, while recurrence in the neck occurred in four. This report further strengthens the need for postsurgical radiation in certain situations."} {"id": "PMID:179394", "title": "Central axis depth dose for a 2.5 MV Van de Graaff generator.", "content": "Central axis percentage depth dose values and isodose curves for the bremsstrahlung beam from a 2.5 MV Van de Graaff generator were measured with a water phantom at 100 cm target-to-surface distance. Tissue-air ratios were calculated from the central axis depth dose data. Use of the 2.5 MV percentage depth dose values are necessary for treatment planning since they are substantially larger than the values given in compilations for 2.0 MV beams.", "contents": "Central axis depth dose for a 2.5 MV Van de Graaff generator. Central axis percentage depth dose values and isodose curves for the bremsstrahlung beam from a 2.5 MV Van de Graaff generator were measured with a water phantom at 100 cm target-to-surface distance. Tissue-air ratios were calculated from the central axis depth dose data. Use of the 2.5 MV percentage depth dose values are necessary for treatment planning since they are substantially larger than the values given in compilations for 2.0 MV beams."} {"id": "PMID:179434", "title": "Significance of glucose tolerance as prognostic sign in hepatectomized patients.", "content": "Glucose tolerance was determined in fourteen patients with cancer of the liver. The patients with parabolic GTT patterns fared relatively better than did those with linear GTT patterns. In the patients with successful extended right hepatectomy, gradually increasing and long-standing hyperglycemia (linear GTT pattern) in response to an oral glucose load was not observed after hepatectomy and the insulin response was significantly greater than that in controls. However, in the patient with unsuccessful extended right hepatectomy, the linear GTT pattern continued for a more prolonged period after hepatectomy.", "contents": "Significance of glucose tolerance as prognostic sign in hepatectomized patients. Glucose tolerance was determined in fourteen patients with cancer of the liver. The patients with parabolic GTT patterns fared relatively better than did those with linear GTT patterns. In the patients with successful extended right hepatectomy, gradually increasing and long-standing hyperglycemia (linear GTT pattern) in response to an oral glucose load was not observed after hepatectomy and the insulin response was significantly greater than that in controls. However, in the patient with unsuccessful extended right hepatectomy, the linear GTT pattern continued for a more prolonged period after hepatectomy."} {"id": "PMID:179435", "title": "Hormone effects on human mammary cancer in organ cultures.", "content": "Specimens of human breast cancers and fibrosarcomas were incubated for 4 to 72 hours as organ cultures. The effect of various concentrations of testosterone, progesterone, and 17-beta-estradiol on cell survival and multiplication was measured as changes in incorporation of H3-TdR into DNA. Both types of tumor reacted to the hormones; both stimulations and inhibitions were recorded. Statistical analysis of data demonstrated possible influence of factors other than hormone treatment. The specificity of hormone sensitivity assays in vitro is questioned.", "contents": "Hormone effects on human mammary cancer in organ cultures. Specimens of human breast cancers and fibrosarcomas were incubated for 4 to 72 hours as organ cultures. The effect of various concentrations of testosterone, progesterone, and 17-beta-estradiol on cell survival and multiplication was measured as changes in incorporation of H3-TdR into DNA. Both types of tumor reacted to the hormones; both stimulations and inhibitions were recorded. Statistical analysis of data demonstrated possible influence of factors other than hormone treatment. The specificity of hormone sensitivity assays in vitro is questioned."} {"id": "PMID:179436", "title": "Total pancreatectomy for ductal carcinoma of the head of the pancreas: current status.", "content": "Because of dismal results after pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas, a review was made of patients treated by total pancreatectomy for this condition. Although the early experience with total pancreatic resection was disappointing, the results during the past decade have been encouraging. Among the forty-two patients reported on with sufficient detail for analysis the operative mortality has been 17 per cent, and the morbidity has been 21 per cent. Sixty-five per cent of these patients (20 of 30) have survived at least one year and 53 per cent (16 of 30) have lived at least two years after surgery. The management of the diabetes and pancreatic insufficiency has not been difficult. Total pancreatectomy appears to be preferable to pancreaticoduodenectomy in the treatment of ductal carcinoma of the head of the pancreas.", "contents": "Total pancreatectomy for ductal carcinoma of the head of the pancreas: current status. Because of dismal results after pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas, a review was made of patients treated by total pancreatectomy for this condition. Although the early experience with total pancreatic resection was disappointing, the results during the past decade have been encouraging. Among the forty-two patients reported on with sufficient detail for analysis the operative mortality has been 17 per cent, and the morbidity has been 21 per cent. Sixty-five per cent of these patients (20 of 30) have survived at least one year and 53 per cent (16 of 30) have lived at least two years after surgery. The management of the diabetes and pancreatic insufficiency has not been difficult. Total pancreatectomy appears to be preferable to pancreaticoduodenectomy in the treatment of ductal carcinoma of the head of the pancreas."} {"id": "PMID:179437", "title": "Giant insulinoma.", "content": "A patient with an extremely large insulinoma but short duration of symptoms is reported on. Fasting hypoglycemia, hyperinsulinism, and angiography were the modalities used to diagnose and locate the tumor.", "contents": "Giant insulinoma. A patient with an extremely large insulinoma but short duration of symptoms is reported on. Fasting hypoglycemia, hyperinsulinism, and angiography were the modalities used to diagnose and locate the tumor."} {"id": "PMID:179449", "title": "Catecholamine-sensitive adenylate cyclase in the developing golden hamster palate.", "content": "The present study was initiated to determine whether specific hormones would influence adenylate cyclase activity within the maxillary-palatal complex during formation of the hamster secondary palate. Stages from initial appearance of the palatal processes to shortly after birth were studied. Highest basal adenylate cyclase activities occurred during the earliest periods of palate development. This basal enzyme activity began to diminish as palatal fusion occurred and remained lowered until birth. Activation of adenylate cyclase by fluoride was maximal at concentrations of 5-10 mM, and was observed throughout the span of palatal development. Fluoride activation of adenylate cyclase was greatest prior to fusion of the palatal processes, then decreased until birth when a slightly increased enzymatic stimulation was seen. Norepinephrine and epinphrine were the catecholamines most capable of inducing increased activation of adenylate cyclase at most periods of palatal growth. Increased enzyme activity in the presence of norepinephrine was more susceptible to antagonism by the beta adrenergic agent, propranolol, than to the alpha adrenergic agent, phentolamine. The remaining catecholamines, namely isoproterenol and dopamine, displayed a lesser ability to activate the enzyme, and adenylate cyclase was not equally responsive to these catecholamines at identical developmental stages. Other hormones, i.e. histamine, serotonin, thyrotropin, growth hormone, thyroxine and glucagon were generally ineffective in activating the enzyme. Phosphodiesterase activity was not detected until shortly before birth.", "contents": "Catecholamine-sensitive adenylate cyclase in the developing golden hamster palate. The present study was initiated to determine whether specific hormones would influence adenylate cyclase activity within the maxillary-palatal complex during formation of the hamster secondary palate. Stages from initial appearance of the palatal processes to shortly after birth were studied. Highest basal adenylate cyclase activities occurred during the earliest periods of palate development. This basal enzyme activity began to diminish as palatal fusion occurred and remained lowered until birth. Activation of adenylate cyclase by fluoride was maximal at concentrations of 5-10 mM, and was observed throughout the span of palatal development. Fluoride activation of adenylate cyclase was greatest prior to fusion of the palatal processes, then decreased until birth when a slightly increased enzymatic stimulation was seen. Norepinephrine and epinphrine were the catecholamines most capable of inducing increased activation of adenylate cyclase at most periods of palatal growth. Increased enzyme activity in the presence of norepinephrine was more susceptible to antagonism by the beta adrenergic agent, propranolol, than to the alpha adrenergic agent, phentolamine. The remaining catecholamines, namely isoproterenol and dopamine, displayed a lesser ability to activate the enzyme, and adenylate cyclase was not equally responsive to these catecholamines at identical developmental stages. Other hormones, i.e. histamine, serotonin, thyrotropin, growth hormone, thyroxine and glucagon were generally ineffective in activating the enzyme. Phosphodiesterase activity was not detected until shortly before birth."} {"id": "PMID:179450", "title": "[Cytochrom P-450. Its value in toxicology. I. Physicochemical and biochemical properties].", "content": "We present the distribution of cytochrome P450, the terminal oxidase of the microsomal drug-metabolizing system among the different species, organs, and its subcellular localization. Physicochemical properties, and more specially spectral properties, of this hemoprotein are reviewed. We also described the two microsomal electron transport chains and the hypothetical cyclic oxidoreduction mechanism of cytochrome P450 in the hydroxylation reactions.", "contents": "[Cytochrom P-450. Its value in toxicology. I. Physicochemical and biochemical properties]. We present the distribution of cytochrome P450, the terminal oxidase of the microsomal drug-metabolizing system among the different species, organs, and its subcellular localization. Physicochemical properties, and more specially spectral properties, of this hemoprotein are reviewed. We also described the two microsomal electron transport chains and the hypothetical cyclic oxidoreduction mechanism of cytochrome P450 in the hydroxylation reactions."} {"id": "PMID:179451", "title": "Immunity to equine herpesvirus type 1 (rhinopneumonitis): in vitro lymphocyte response.", "content": "Twenty-two ponies were examined for serum-neutralizing (SN) antibody to equine herpesvirus type 1 and for in vitro lymphocyte transformation in the presence of viral antigen. Six ponies had undetectable levels of neutralizing antibody (titer less than 1:2) and had lymphocytes which did not respond in culture with viral antigen (stimulation index less than 2.0). Four ponies which had SN antibody to equine herpesvirus type 1 did not manifest lymphocyte transformation in vitro. The 12 remaining seropositive ponies had lymphocyte transformation with viral antigen in vitro (stimulation indexes from 2.0 to 23.5). Lymphocyte transformation was specifically suppressed when cells were grown in medium containing autologous serum. The temporal development of in vitro lymphocyte responsiveness and SN antibody in 3 specific-pathogenfree ponies after experimentally induced infection with equine herpesvirus type 1 is described.", "contents": "Immunity to equine herpesvirus type 1 (rhinopneumonitis): in vitro lymphocyte response. Twenty-two ponies were examined for serum-neutralizing (SN) antibody to equine herpesvirus type 1 and for in vitro lymphocyte transformation in the presence of viral antigen. Six ponies had undetectable levels of neutralizing antibody (titer less than 1:2) and had lymphocytes which did not respond in culture with viral antigen (stimulation index less than 2.0). Four ponies which had SN antibody to equine herpesvirus type 1 did not manifest lymphocyte transformation in vitro. The 12 remaining seropositive ponies had lymphocyte transformation with viral antigen in vitro (stimulation indexes from 2.0 to 23.5). Lymphocyte transformation was specifically suppressed when cells were grown in medium containing autologous serum. The temporal development of in vitro lymphocyte responsiveness and SN antibody in 3 specific-pathogenfree ponies after experimentally induced infection with equine herpesvirus type 1 is described."} {"id": "PMID:179452", "title": "Experimental placental transfer of foot-and-mouth disease virus in mice.", "content": "An attenuated type O foot-and-mouth disease (FMD) virus which was virulent for infant, but not for pregnant, mice proved to be superior to a virulent type C FMD virus in the development of a model system for the study of placental transfer of FMD in mice. When mice were inoculated at day 8 or 12 of gestation with type O FMD virus, the virus was detectable in the maternal pancreas for 3 days and in the placenta for 6 days. Viral levels in the fetus and the amniotic fluid were inconsistent and were apparently due to a spillover from the placental infection. The elimination of the virus from the placenta coincided with the expected production of maternal 7S antibody. Mice inoculated from days 0 to 12 of gestation did not have a significant increase in dead young by day 18 (the day of necropsy). Similarly inoculated mice, when permitted to go to term, produced and raised normal-size litters. Inoculation on day 15 of gestation resulted in an increased number of deaths due to morbidity of the dams. It was concluded that the placenta serves as an active site of infection for FMD virus in pregnant mice, but the fetus is relatively resistant to infection.", "contents": "Experimental placental transfer of foot-and-mouth disease virus in mice. An attenuated type O foot-and-mouth disease (FMD) virus which was virulent for infant, but not for pregnant, mice proved to be superior to a virulent type C FMD virus in the development of a model system for the study of placental transfer of FMD in mice. When mice were inoculated at day 8 or 12 of gestation with type O FMD virus, the virus was detectable in the maternal pancreas for 3 days and in the placenta for 6 days. Viral levels in the fetus and the amniotic fluid were inconsistent and were apparently due to a spillover from the placental infection. The elimination of the virus from the placenta coincided with the expected production of maternal 7S antibody. Mice inoculated from days 0 to 12 of gestation did not have a significant increase in dead young by day 18 (the day of necropsy). Similarly inoculated mice, when permitted to go to term, produced and raised normal-size litters. Inoculation on day 15 of gestation resulted in an increased number of deaths due to morbidity of the dams. It was concluded that the placenta serves as an active site of infection for FMD virus in pregnant mice, but the fetus is relatively resistant to infection."} {"id": "PMID:179456", "title": "Functional possibilities for aminoacylation of viral RNA in transcription and translation.", "content": "RNA from at least ten viruses, representing more than four different group, is known to specifically bind in amino acid in a tRNA-like manner. The biological function of aminoacylation of RNA from these viruses and of tRNA association with tumor viruses and bacteriophage, is discussed. Hypothetical schemes are presented for a role for aminoacylation in viral translational and transcriptional mechanisms, and the current evidence relating to these models is presented.", "contents": "Functional possibilities for aminoacylation of viral RNA in transcription and translation. RNA from at least ten viruses, representing more than four different group, is known to specifically bind in amino acid in a tRNA-like manner. The biological function of aminoacylation of RNA from these viruses and of tRNA association with tumor viruses and bacteriophage, is discussed. Hypothetical schemes are presented for a role for aminoacylation in viral translational and transcriptional mechanisms, and the current evidence relating to these models is presented."} {"id": "PMID:179457", "title": "Interactions of plant viral RNAs and tRNA nucleotidyl transferase.", "content": "Ribonucleic acid from TMV and BMV can accept AMP and CMP when digested with VPD. This incorporation is catalyzed by E. coli and yeast tRNA nucleotidyl transferases. Complex formation is obtained between TYMV RNA and tRNA nucleotidyl transferase in sucrose gradients while TMV and BMV RNAs failed to form a complex in the same conditions. The affinity of the enzyme for viral RNAs is lower than the affinity for tRNA as shown by complex formation on nitrocellulose filters and competition with tRNA. Coat protein from TMV particles enhances AMP and CMP incorporation onto tRNA catalyzed by the E. coli tRNA nucleotidyl transferase.", "contents": "Interactions of plant viral RNAs and tRNA nucleotidyl transferase. Ribonucleic acid from TMV and BMV can accept AMP and CMP when digested with VPD. This incorporation is catalyzed by E. coli and yeast tRNA nucleotidyl transferases. Complex formation is obtained between TYMV RNA and tRNA nucleotidyl transferase in sucrose gradients while TMV and BMV RNAs failed to form a complex in the same conditions. The affinity of the enzyme for viral RNAs is lower than the affinity for tRNA as shown by complex formation on nitrocellulose filters and competition with tRNA. Coat protein from TMV particles enhances AMP and CMP incorporation onto tRNA catalyzed by the E. coli tRNA nucleotidyl transferase."} {"id": "PMID:179459", "title": "[Reticulohistiocytosis of benign evolution (Hashimoto-Pritzker type). Electron microscopy study].", "content": "We describe a rare form of histiocytosis, characterized by numerous tumoral lesions of the skin appearing at birth and desappearing spontaneously within 2 month without visceral lesions and without systemic symptoms. Light microscopy shows histiocytes, some of which contain an irregular nucleus with a spumous cytoplasm surrounded by many red blood cells. Electron microscopy shows myelinoid inclusions in the histiocyte cytoplasm and \"vermiform\" bodies. In our opinion, a similar anatomoclinical entity was described for the first time and only once by Hashimoto and Pritzker.", "contents": "[Reticulohistiocytosis of benign evolution (Hashimoto-Pritzker type). Electron microscopy study]. We describe a rare form of histiocytosis, characterized by numerous tumoral lesions of the skin appearing at birth and desappearing spontaneously within 2 month without visceral lesions and without systemic symptoms. Light microscopy shows histiocytes, some of which contain an irregular nucleus with a spumous cytoplasm surrounded by many red blood cells. Electron microscopy shows myelinoid inclusions in the histiocyte cytoplasm and \"vermiform\" bodies. In our opinion, a similar anatomoclinical entity was described for the first time and only once by Hashimoto and Pritzker."} {"id": "PMID:179460", "title": "[Examination of the peripheral blood in 100 dermatology cases].", "content": "Routine examination under the electron microscope of lymphocytes from peripheral blood in 100 patients with skin disease and 20 healthly controls, was carried out seeking branched tubular inclusions of lupus type and lymphocytes with an indented or cribriform nucleus, and gave the following results: -Presence of inclusions of lupus type in 8 cases (4 cases of systemic lupus out of 15 examined, 1 case of sclerodermatomyositis, 3 lymphomas of the skin). These results confirm previous studies carried out in cases of collagen disease and, in addition, demonstrate branched tubular inclusions in lymphomas, they emphasize the importance of the lymphocyte as common denominator in man, in both auto-immune diseases and in lymphoma.-The presence of cells with an indented, or cribriform nucleus in 12 cases out of 100 patients (8 cases of S\u00e9zary syndrome out of 8; 4 cases of mycosis fungoides out of 12). Lymphoma deposits were never found outside the skin. -A second type of cytoplasmiclymphocytic inclusion, with a lamellar appearance, has already been described by Hovig and was noted in 13 cases out of 120 biopsies in various diseases and in 2 healthy controls. These were perhaps artifacts.", "contents": "[Examination of the peripheral blood in 100 dermatology cases]. Routine examination under the electron microscope of lymphocytes from peripheral blood in 100 patients with skin disease and 20 healthly controls, was carried out seeking branched tubular inclusions of lupus type and lymphocytes with an indented or cribriform nucleus, and gave the following results: -Presence of inclusions of lupus type in 8 cases (4 cases of systemic lupus out of 15 examined, 1 case of sclerodermatomyositis, 3 lymphomas of the skin). These results confirm previous studies carried out in cases of collagen disease and, in addition, demonstrate branched tubular inclusions in lymphomas, they emphasize the importance of the lymphocyte as common denominator in man, in both auto-immune diseases and in lymphoma.-The presence of cells with an indented, or cribriform nucleus in 12 cases out of 100 patients (8 cases of S\u00e9zary syndrome out of 8; 4 cases of mycosis fungoides out of 12). Lymphoma deposits were never found outside the skin. -A second type of cytoplasmiclymphocytic inclusion, with a lamellar appearance, has already been described by Hovig and was noted in 13 cases out of 120 biopsies in various diseases and in 2 healthy controls. These were perhaps artifacts."} {"id": "PMID:179461", "title": "[Importance of replacing the support medium for viral interferonogenesis in tissue culture].", "content": "Interferonogenesis in the cells of chick embryos induced by strain Lee of influenza B virus was studied. The levels of interferon production with and without changing the medium before the cell inoculation with the interferonogens were compared. It was shown that preliminary changing of the medium resulted in a statistically reliable increase in production of interferon as compared to that without the medium changing. It was found that the increase in the synthesis of interferon under the conditions of the maintaining medium changing was accompanied by an increase in the levels of synthesis of the cellular protein and RNA determined by incorporation of C14-leucine and H3-uridine into the acid insoluble fraction of the cells. It is concluded that metabolic changes in the cells at the moment of interferonogenesis induction due to the maintaining medium changing should be considered in estimation of the experiments on the mechanism of the virus induced interferonogenesis in the tissue culture.", "contents": "[Importance of replacing the support medium for viral interferonogenesis in tissue culture]. Interferonogenesis in the cells of chick embryos induced by strain Lee of influenza B virus was studied. The levels of interferon production with and without changing the medium before the cell inoculation with the interferonogens were compared. It was shown that preliminary changing of the medium resulted in a statistically reliable increase in production of interferon as compared to that without the medium changing. It was found that the increase in the synthesis of interferon under the conditions of the maintaining medium changing was accompanied by an increase in the levels of synthesis of the cellular protein and RNA determined by incorporation of C14-leucine and H3-uridine into the acid insoluble fraction of the cells. It is concluded that metabolic changes in the cells at the moment of interferonogenesis induction due to the maintaining medium changing should be considered in estimation of the experiments on the mechanism of the virus induced interferonogenesis in the tissue culture."} {"id": "PMID:179462", "title": "[Sensitivity of various races of the tularemia microbe to erythromycin, oleandomycin and polymyxin].", "content": "Sensitivity of 66 strains of the tularemia microbe to erythromycin, oleandomycin and polymyxin was studied. It was shown that all the strains were resistant to polymyxin. The strains of the non-artic and Central Asiatic races and 64 per cent of the strains of the holarctic race were resistant to erythromycin and oleandomycin.", "contents": "[Sensitivity of various races of the tularemia microbe to erythromycin, oleandomycin and polymyxin]. Sensitivity of 66 strains of the tularemia microbe to erythromycin, oleandomycin and polymyxin was studied. It was shown that all the strains were resistant to polymyxin. The strains of the non-artic and Central Asiatic races and 64 per cent of the strains of the holarctic race were resistant to erythromycin and oleandomycin."} {"id": "PMID:179463", "title": "[Study of C1. perfringens resistance to lincomycin].", "content": "A possibility of developing resistant forms of C1. perfringens during treatment of experimental anaerobic (gaseous) infection with lincomycin was studied. It was shown that treatment of the animals for 7 days resulted in an increase in the resistance by 33-41 times. It was noted that strains with decreased sensitivity to lincomycins had changed morphology and biochemical activity (decreased lecitinase activity, changed biochemical properties), decreased virulence and pathogenicity for animals. So as to obtain the protective effect of the antibiotics in experimental anaerobic (gaseous) infection caused by resistant variants of C1. perfringens it was necessary to increase 1.5-3 times the doses of lincomycin or chlolincocin as compared to the processes induced by sensitive strains.", "contents": "[Study of C1. perfringens resistance to lincomycin]. A possibility of developing resistant forms of C1. perfringens during treatment of experimental anaerobic (gaseous) infection with lincomycin was studied. It was shown that treatment of the animals for 7 days resulted in an increase in the resistance by 33-41 times. It was noted that strains with decreased sensitivity to lincomycins had changed morphology and biochemical activity (decreased lecitinase activity, changed biochemical properties), decreased virulence and pathogenicity for animals. So as to obtain the protective effect of the antibiotics in experimental anaerobic (gaseous) infection caused by resistant variants of C1. perfringens it was necessary to increase 1.5-3 times the doses of lincomycin or chlolincocin as compared to the processes induced by sensitive strains."} {"id": "PMID:179465", "title": "[Quantitative determination of anhydroleandomycin and glycol in oleandomycin phosphate].", "content": "A spectrophotometric method for determination of inactive admixtures in oleandomycin phosphate-anhydrooleandomycin was developed. The method was based on measuring optical density of methanol solutions of oleandomycin and its admixtures at a wave length of 235 nm of UV-spectrum. The minimun detectable amount was 0.5 per cent. A method of thin-layer chromatography in a buffered fixed layer was developed for determination of the 2nd inactive admixture, i.e. glycole. The chromatogrammes were developed with xanthydrol. The minimum detectable amount was 3 mug.", "contents": "[Quantitative determination of anhydroleandomycin and glycol in oleandomycin phosphate]. A spectrophotometric method for determination of inactive admixtures in oleandomycin phosphate-anhydrooleandomycin was developed. The method was based on measuring optical density of methanol solutions of oleandomycin and its admixtures at a wave length of 235 nm of UV-spectrum. The minimun detectable amount was 0.5 per cent. A method of thin-layer chromatography in a buffered fixed layer was developed for determination of the 2nd inactive admixture, i.e. glycole. The chromatogrammes were developed with xanthydrol. The minimum detectable amount was 3 mug."} {"id": "PMID:179466", "title": "[Effect of migillin on protein synthesis in intact and virally infected TKCE and FL cells].", "content": "The effect of migillin was studied with respect to protein synthesis in the cells of TKCE (transplantable line of cells of the kidneys of cow embryos) and FL--intact and infected with viruses of aphtous fever A22, strain 550 and poliomyelitis of type III, strain Saukett respectively. Simultaneously the effect of migillin on sensitivity of the cells to the above viruses was tested. The synthesis of protein was determined by incorporation of C14-glycine into the acid insoluble fraction of the cells. It was found that protein synthesis significantly increased under the effect of migillin in both the intact cells and the cells infected with the viruses. The viruses of aphtous fever and poliomyelitis inhibited the synthesis of proteins. The antibiotic increased the activity of dehydrogenases and respiration of HEp-2 cells. Migillin markedly suppressed reproduction of the poliomyelitis virus, the effect on the virus of aphtous fever was lower in the cell culture. In guinea pigs the antiviral effect of the antibiotic resulted in prolongation of the incubation period and retardation of the aphtous fever process generalization. The results of the experiments showed that migillin stimulated the activity of dehydrogenases, respiration, protein synthesis in the cell cultures and possessed antiviral activity in vitro and in vivo.", "contents": "[Effect of migillin on protein synthesis in intact and virally infected TKCE and FL cells]. The effect of migillin was studied with respect to protein synthesis in the cells of TKCE (transplantable line of cells of the kidneys of cow embryos) and FL--intact and infected with viruses of aphtous fever A22, strain 550 and poliomyelitis of type III, strain Saukett respectively. Simultaneously the effect of migillin on sensitivity of the cells to the above viruses was tested. The synthesis of protein was determined by incorporation of C14-glycine into the acid insoluble fraction of the cells. It was found that protein synthesis significantly increased under the effect of migillin in both the intact cells and the cells infected with the viruses. The viruses of aphtous fever and poliomyelitis inhibited the synthesis of proteins. The antibiotic increased the activity of dehydrogenases and respiration of HEp-2 cells. Migillin markedly suppressed reproduction of the poliomyelitis virus, the effect on the virus of aphtous fever was lower in the cell culture. In guinea pigs the antiviral effect of the antibiotic resulted in prolongation of the incubation period and retardation of the aphtous fever process generalization. The results of the experiments showed that migillin stimulated the activity of dehydrogenases, respiration, protein synthesis in the cell cultures and possessed antiviral activity in vitro and in vivo."} {"id": "PMID:179476", "title": "Vincristine toxicity unrelated to dose.", "content": "Four children with vincristine toxicity unrelated to dose are described. Fever, haematological toxicity, and abdominal distension occurred 2-7 days after vincristine was given. Convulsions occurred 6-8 days after vincristine in all 4. Inappropriate secretion of antidiuretic hormone was thought to have occurred in 3 patients. 2 patients died during the acute toxicity phase. Necropsy findings did not show neuronal changes which could be directly ascribed to vincristine.", "contents": "Vincristine toxicity unrelated to dose. Four children with vincristine toxicity unrelated to dose are described. Fever, haematological toxicity, and abdominal distension occurred 2-7 days after vincristine was given. Convulsions occurred 6-8 days after vincristine in all 4. Inappropriate secretion of antidiuretic hormone was thought to have occurred in 3 patients. 2 patients died during the acute toxicity phase. Necropsy findings did not show neuronal changes which could be directly ascribed to vincristine."} {"id": "PMID:179477", "title": "Freeze-etching observations of herpes simplex virus.", "content": "Herpes simplex virus isolated from the cheek lesions of a patient was propagated on FL cells. Pellets of infected cells were cryoprotected with glycerol, and processed for freeze-etching. Viral nucleocapsids were observed in the nucleus of FL cells. The cores were observed in three forms. Capsomeres were clearly shown. Release of virus particles from the nucleus and the plasmalemma was more clearly observed. Myeloid figures and lipid droplets were also found. The significance of these findings is discussed.", "contents": "Freeze-etching observations of herpes simplex virus. Herpes simplex virus isolated from the cheek lesions of a patient was propagated on FL cells. Pellets of infected cells were cryoprotected with glycerol, and processed for freeze-etching. Viral nucleocapsids were observed in the nucleus of FL cells. The cores were observed in three forms. Capsomeres were clearly shown. Release of virus particles from the nucleus and the plasmalemma was more clearly observed. Myeloid figures and lipid droplets were also found. The significance of these findings is discussed."} {"id": "PMID:179478", "title": "Effects of melanocyte stimulating hormone and theophylline on human melanocytes in vitro.", "content": "The effects of MSH on the human melanocyte in vitro were studied. The addition of MSH up to the concentration of 40 mug/ml into the culture medium did not produce appreciable change on the morphology of the melanocyte. The melanocyte, however, responded to the simultaneous addition of MSH and theophylline with marked increase in the length and complexity of the dendritic process. Melanin synthesis, as indicated by the uptake of tyrosine in the presence of an inhibitor of protein synthesis, was remarkably activated by the simultaneous addition of MSH and theophylline. MSH alone activated the melanin synthesis only slightly, but the increase in the uptake of tyrosine was significant statistically. These results were discussed in terms of the MSH-cyclic AMP cascade in which theophylline worked as an inhibitor of cyclic AMP phosphodiesterase, and increased the intracellular level of cyclic AMP by inhibiting catabolism of cyclic AMP.", "contents": "Effects of melanocyte stimulating hormone and theophylline on human melanocytes in vitro. The effects of MSH on the human melanocyte in vitro were studied. The addition of MSH up to the concentration of 40 mug/ml into the culture medium did not produce appreciable change on the morphology of the melanocyte. The melanocyte, however, responded to the simultaneous addition of MSH and theophylline with marked increase in the length and complexity of the dendritic process. Melanin synthesis, as indicated by the uptake of tyrosine in the presence of an inhibitor of protein synthesis, was remarkably activated by the simultaneous addition of MSH and theophylline. MSH alone activated the melanin synthesis only slightly, but the increase in the uptake of tyrosine was significant statistically. These results were discussed in terms of the MSH-cyclic AMP cascade in which theophylline worked as an inhibitor of cyclic AMP phosphodiesterase, and increased the intracellular level of cyclic AMP by inhibiting catabolism of cyclic AMP."} {"id": "PMID:179483", "title": "Functional tumors of the organ of Zuckerkandl.", "content": "Chromaffin-reacting pheochromocytomas of the adrenal medulla are the most frequently encountered functional paraganglionic neoplasms. However, extra-adrenal pheochromocytomas as well as non-chromaffin paragangliomas, including those of the carotid body and glomus jugulare, may produce symptoms from catecholamine secretion. One of the extra-adrenal sites from which these tumors arise is from a collection of para-aortic, paraganglion cells around the origin of the inferior mesenteric artery. This collection of paraganglia was described in fetuses by Zuckerkandl in 1901 and has subsequently been referred to as the organ of Zuckerkandl. The diagnosis and management of these neoplasms differ somewhat from that of adrenal pheochromocytomas, but excellent results are often obtained by excision of these lesions. Four patients with functional tumors of the organ of Zuckerkandl are reviewed together with the other reported cases in the literature.", "contents": "Functional tumors of the organ of Zuckerkandl. Chromaffin-reacting pheochromocytomas of the adrenal medulla are the most frequently encountered functional paraganglionic neoplasms. However, extra-adrenal pheochromocytomas as well as non-chromaffin paragangliomas, including those of the carotid body and glomus jugulare, may produce symptoms from catecholamine secretion. One of the extra-adrenal sites from which these tumors arise is from a collection of para-aortic, paraganglion cells around the origin of the inferior mesenteric artery. This collection of paraganglia was described in fetuses by Zuckerkandl in 1901 and has subsequently been referred to as the organ of Zuckerkandl. The diagnosis and management of these neoplasms differ somewhat from that of adrenal pheochromocytomas, but excellent results are often obtained by excision of these lesions. Four patients with functional tumors of the organ of Zuckerkandl are reviewed together with the other reported cases in the literature."} {"id": "PMID:179484", "title": "Immunocompetence of patients with bronchogenic carcinoma.", "content": "Patients with lung carcinoma were tested for number of circulating thymus-derived (T-)lymphocytes and lymphocyte cytotoxicity before treatment and following operation or radiation therapy or a combination of the two. The proportion of circulating T-lymphocytes in healthy individuals was 75%, and the T-lymphocyte level was 1, 460 per cubic millimeter. All patients with lung cancer had a significantly decreased percentage and absolute number of T-cells before any treatment. Patients tested six to eight weeks following pneumonectomy or lobectomy showed an increased proportion of circulating T-cells in comparison to pretreatment values. Functional activity of immune lymphocytes as shown by cytotoxicity assay also improved in comparison to pretreatment values. The potential value of tests for immunocompetence is discussed.", "contents": "Immunocompetence of patients with bronchogenic carcinoma. Patients with lung carcinoma were tested for number of circulating thymus-derived (T-)lymphocytes and lymphocyte cytotoxicity before treatment and following operation or radiation therapy or a combination of the two. The proportion of circulating T-lymphocytes in healthy individuals was 75%, and the T-lymphocyte level was 1, 460 per cubic millimeter. All patients with lung cancer had a significantly decreased percentage and absolute number of T-cells before any treatment. Patients tested six to eight weeks following pneumonectomy or lobectomy showed an increased proportion of circulating T-cells in comparison to pretreatment values. Functional activity of immune lymphocytes as shown by cytotoxicity assay also improved in comparison to pretreatment values. The potential value of tests for immunocompetence is discussed."} {"id": "PMID:179485", "title": "Sleep patterns and gastric acid secretion in duodenal ucler disease.", "content": "Five normal volunteers and five patients with duodenal ulcer (DU) disease were studied for five consecutive nights. All subjects underwent placement of a nasogastric tube, continuous collection of gastric juice, and continuous electroencephalographic monitoring of sleep. Gastric juice was collected in 20-minute samples by remote suction (Gomco). Blood samples were drawn every 20 minutes on the third night via an indwelling venous needle. Results showed no significant correlations between the sleep variables and the gastric acid secretion measures or between the sleep variables and serum gastrin levels. Acid secretion decreased from hour 1 to hour 2 in controls and in patients with inactive DU disease, while it increased in patients with active DU disease. Each subject had at least one night of recording in which continuous gastric secretion was less than 0.1 mEq per 20-minute sample. It appears unlikely that the gastric discomfort of DU patients can be attributed to acid hypersecretion triggered by rapid eye movement sleep.", "contents": "Sleep patterns and gastric acid secretion in duodenal ucler disease. Five normal volunteers and five patients with duodenal ulcer (DU) disease were studied for five consecutive nights. All subjects underwent placement of a nasogastric tube, continuous collection of gastric juice, and continuous electroencephalographic monitoring of sleep. Gastric juice was collected in 20-minute samples by remote suction (Gomco). Blood samples were drawn every 20 minutes on the third night via an indwelling venous needle. Results showed no significant correlations between the sleep variables and the gastric acid secretion measures or between the sleep variables and serum gastrin levels. Acid secretion decreased from hour 1 to hour 2 in controls and in patients with inactive DU disease, while it increased in patients with active DU disease. Each subject had at least one night of recording in which continuous gastric secretion was less than 0.1 mEq per 20-minute sample. It appears unlikely that the gastric discomfort of DU patients can be attributed to acid hypersecretion triggered by rapid eye movement sleep."} {"id": "PMID:179486", "title": "Oxidative phosphorylation in Micrococcus denitrificans: calculation of the P/O ratio in growing cells.", "content": "P/O ratios were measured in membrane particles obtained from cells of Micrococcus denitrificans, while growing on different carbon sources. The membrane particles obtained from cells growing actively on glucose, succinate, ethanol and propanol as the carbon and energy sources catalyzed oxidative phosphorylation and yielded respective P/O ratios of 1.4, 1.2, 0.8, and 0.5 with NADH, and 0.8, 0.6, 0.6, and 0.5 with succinate as the electron donors. Not such a difference in P/O ratio is observed in intact resting cells grown with different carbon sources. It is concluded that the influence of the carbon source is probably directed towards the efficiency of oxidative phosphorylation in membrane particles and not in the growing cells. For the aerobic carbon source-limited chemostat cultures the following maximum growth yields were determined: 40.2 and 34.2 for succinate and oxygen, 41.7 and 36.5 for malate and oxygen, 81.4 and 39.4 for mannitol and oxygen, and 77.8 and 43.4 for gluconate and oxygen respectively. With a mathematical model (de Kwaadsteniet et al., in press) the P/O ratio was valued at 1.4-1.7. YATP at mu=0.2 was valued at 8.7-10.9; YmaxATP at 9.6-13.2 and me at 0.6-4.5 for the most precise experiment (gluconate-limited). The calculation of these growth parameters has been discussed.", "contents": "Oxidative phosphorylation in Micrococcus denitrificans: calculation of the P/O ratio in growing cells. P/O ratios were measured in membrane particles obtained from cells of Micrococcus denitrificans, while growing on different carbon sources. The membrane particles obtained from cells growing actively on glucose, succinate, ethanol and propanol as the carbon and energy sources catalyzed oxidative phosphorylation and yielded respective P/O ratios of 1.4, 1.2, 0.8, and 0.5 with NADH, and 0.8, 0.6, 0.6, and 0.5 with succinate as the electron donors. Not such a difference in P/O ratio is observed in intact resting cells grown with different carbon sources. It is concluded that the influence of the carbon source is probably directed towards the efficiency of oxidative phosphorylation in membrane particles and not in the growing cells. For the aerobic carbon source-limited chemostat cultures the following maximum growth yields were determined: 40.2 and 34.2 for succinate and oxygen, 41.7 and 36.5 for malate and oxygen, 81.4 and 39.4 for mannitol and oxygen, and 77.8 and 43.4 for gluconate and oxygen respectively. With a mathematical model (de Kwaadsteniet et al., in press) the P/O ratio was valued at 1.4-1.7. YATP at mu=0.2 was valued at 8.7-10.9; YmaxATP at 9.6-13.2 and me at 0.6-4.5 for the most precise experiment (gluconate-limited). The calculation of these growth parameters has been discussed."} {"id": "PMID:179487", "title": "Influence of several nucleotides on the competence development of Bacillus subtilis.", "content": "The influence of adenosine-3',5'-cyclic monophosphate (cAMP) and other nucleotides on the competence development of Bacillus subtilis was studied. The stimulation of competence which can be achieved by exposing physiologically low-competent cells to supernatants from highly competent cultures can be inhibited with different cAMP doses. When the same cells were suspended in a minimal medium with cAMP, varying degrees of stimulatin- of competence were observed depending on the time of addition of the drug. This effect is not specific for cAMP. It appears to be correlated to an increase of the amount of DNA bound to the competent cells. cAMP activities were antagonized by equimolar doses of adenosine-triphosphate (ATP) and guanosine-triphosphate (GTP).", "contents": "Influence of several nucleotides on the competence development of Bacillus subtilis. The influence of adenosine-3',5'-cyclic monophosphate (cAMP) and other nucleotides on the competence development of Bacillus subtilis was studied. The stimulation of competence which can be achieved by exposing physiologically low-competent cells to supernatants from highly competent cultures can be inhibited with different cAMP doses. When the same cells were suspended in a minimal medium with cAMP, varying degrees of stimulatin- of competence were observed depending on the time of addition of the drug. This effect is not specific for cAMP. It appears to be correlated to an increase of the amount of DNA bound to the competent cells. cAMP activities were antagonized by equimolar doses of adenosine-triphosphate (ATP) and guanosine-triphosphate (GTP)."} {"id": "PMID:179488", "title": "Energy metabolism of Bdellovibrio bacteriovorus. II. P/O ratio and ATP pool turnover rate.", "content": "The P/O ratio of Bdellovibrio bacteriovorus, strain Bd 109 Sa, was evaluated by two different methods based on the determination of energy-rich phosphate bonds and either NADH oxidation or oxygen-uptake. P/O values calculated on the basis of NADH oxidation were up to 6, which has to be regarded as being overestimated. P/O values calculated from energy-rich phosphate bonds and oxygen uptake were around 2. The P/O values determined for Escherichia coli B were similar. The loss of phosphorylation efficiency at one site is discussed. The ATP pool turnover rate of Bdellovibrio was 8/min during endogenous respiration and 24/min during substrate respiration. The corresponding values in Escherichia coli B were 3/min and 38/min.", "contents": "Energy metabolism of Bdellovibrio bacteriovorus. II. P/O ratio and ATP pool turnover rate. The P/O ratio of Bdellovibrio bacteriovorus, strain Bd 109 Sa, was evaluated by two different methods based on the determination of energy-rich phosphate bonds and either NADH oxidation or oxygen-uptake. P/O values calculated on the basis of NADH oxidation were up to 6, which has to be regarded as being overestimated. P/O values calculated from energy-rich phosphate bonds and oxygen uptake were around 2. The P/O values determined for Escherichia coli B were similar. The loss of phosphorylation efficiency at one site is discussed. The ATP pool turnover rate of Bdellovibrio was 8/min during endogenous respiration and 24/min during substrate respiration. The corresponding values in Escherichia coli B were 3/min and 38/min."} {"id": "PMID:179489", "title": "The effect of glucose and manganese on adenosine-3',5'-monophosphate levels during growth and differentiation of Aspergillus nidulans.", "content": "The role of cyclic adenosine monophosphate (cAMP) during growth and development of Aspergillus nidulans was investigated. In normal cultures the highest amount of cAMP, expressed on a dry weight basis, was found after 24 h of growth when still more than 5% glucose was present in the medium. After depletion of the medium even a slight fall in cAMP was noted. Glucose concentrations ranging from 0.5-12% resulted in a slight decrease in the amount of cAMP as measured after 24 h of growth. Cultures with manganese deficiency resulted in a low cAMP level after 24 h of growth. However, the exhaustion of glucose in the absence of manganese was connected with a sharp increase in cAMP. This indicates that manganese shortage was not a direct cause of the low cAMP level after 24 h. The amount of cAMP rose with increasing concentration of manganese in the medium until a maximum at 0.25 muM. It is tempting to speculate that this rise in cAMP in the manganese deficient culture is explained by the absence of glucose, that in the control culture is derived from the breakdown of the reserve material alpha-1,3-glucan. Addition of manganese after glucose exhaustion to a manganese deficient culture induced cleistothecium formation. However, they contained only a few ascospores indicating the importance of alpha-1,3-glucan as a carbon and energy source for ascospore formation. The regulation of the level of cAMP by the transport of glucose into the cell or its intracellular concentration is discussed.", "contents": "The effect of glucose and manganese on adenosine-3',5'-monophosphate levels during growth and differentiation of Aspergillus nidulans. The role of cyclic adenosine monophosphate (cAMP) during growth and development of Aspergillus nidulans was investigated. In normal cultures the highest amount of cAMP, expressed on a dry weight basis, was found after 24 h of growth when still more than 5% glucose was present in the medium. After depletion of the medium even a slight fall in cAMP was noted. Glucose concentrations ranging from 0.5-12% resulted in a slight decrease in the amount of cAMP as measured after 24 h of growth. Cultures with manganese deficiency resulted in a low cAMP level after 24 h of growth. However, the exhaustion of glucose in the absence of manganese was connected with a sharp increase in cAMP. This indicates that manganese shortage was not a direct cause of the low cAMP level after 24 h. The amount of cAMP rose with increasing concentration of manganese in the medium until a maximum at 0.25 muM. It is tempting to speculate that this rise in cAMP in the manganese deficient culture is explained by the absence of glucose, that in the control culture is derived from the breakdown of the reserve material alpha-1,3-glucan. Addition of manganese after glucose exhaustion to a manganese deficient culture induced cleistothecium formation. However, they contained only a few ascospores indicating the importance of alpha-1,3-glucan as a carbon and energy source for ascospore formation. The regulation of the level of cAMP by the transport of glucose into the cell or its intracellular concentration is discussed."} {"id": "PMID:179490", "title": "[Histological and electron microscopy studies on the adenocarcinomatosis of laying hens].", "content": "Histological examination of 187 tumours from 98 hens (laying hybrids of various lines, age 80-123 weeks) showed that highly-differentiated tubulo-alveolar adenocarcinoma was present in 95% of the birds; in 20% it had a scirrhus structure. Histological and ultrastructural features of these carcinomas and their tendency to form secretory granules pointed to an origin from the protein-secreting part of the oviduct (magnum). In the remaining 5% of birds there were non-specific adenocarcinomas (probably ovarian carcinoma) and mesotheliomas.", "contents": "[Histological and electron microscopy studies on the adenocarcinomatosis of laying hens]. Histological examination of 187 tumours from 98 hens (laying hybrids of various lines, age 80-123 weeks) showed that highly-differentiated tubulo-alveolar adenocarcinoma was present in 95% of the birds; in 20% it had a scirrhus structure. Histological and ultrastructural features of these carcinomas and their tendency to form secretory granules pointed to an origin from the protein-secreting part of the oviduct (magnum). In the remaining 5% of birds there were non-specific adenocarcinomas (probably ovarian carcinoma) and mesotheliomas."} {"id": "PMID:179491", "title": "Primary Krukenberg tumour in pregnancy.", "content": "The literature on primary Krukenberg tumours in pregnancy is reviewed. 6 cases are reported and all could be accepted as complying with the international classification of primary ovarian tumours. An additional case is presented with mostly osteoplastic metastases and necrosis of the marrow.", "contents": "Primary Krukenberg tumour in pregnancy. The literature on primary Krukenberg tumours in pregnancy is reviewed. 6 cases are reported and all could be accepted as complying with the international classification of primary ovarian tumours. An additional case is presented with mostly osteoplastic metastases and necrosis of the marrow."} {"id": "PMID:179492", "title": "[C-type-like particles in normal human placentas (author's transl)].", "content": "Evidence is presented for the presence of C-type-like particles in the syncytiotrophoblast of normal human placentas. In 10 of 110 mainly immature placentas studied both extracellular and budding particles were found.", "contents": "[C-type-like particles in normal human placentas (author's transl)]. Evidence is presented for the presence of C-type-like particles in the syncytiotrophoblast of normal human placentas. In 10 of 110 mainly immature placentas studied both extracellular and budding particles were found."} {"id": "PMID:179493", "title": "Local effects of silica on tumor growth inhibition. A histological study.", "content": "The subcutaneous implant of a fibrosarcoma covered with silica, in rats, resulted in a temporary retardation of tumor growth. The histological study demonstrated that the silica provoked, within and at the periphery of the tumor, inflammatory foci which altered the composition of the fundamental substance and which promoted the accumulation of principally macrophages in the interior as well as on the surface of the tumoral mass. Besides the macrophages of the host, a number of tumor cells do also phagocyte silica crystals, leading to destruction of all those cells. The authors are of the opinion that the local modifications provoked by silica, could have interfered in the adaptation of the tumor with its nutrient stroma. Of these modifications, the stroma sclerosis seems to be the most effective in the inhibition of tumor growth. Some correlations were suggested between the here described results and those obtained by other workers who have used other inflammatory agents of different nature.", "contents": "Local effects of silica on tumor growth inhibition. A histological study. The subcutaneous implant of a fibrosarcoma covered with silica, in rats, resulted in a temporary retardation of tumor growth. The histological study demonstrated that the silica provoked, within and at the periphery of the tumor, inflammatory foci which altered the composition of the fundamental substance and which promoted the accumulation of principally macrophages in the interior as well as on the surface of the tumoral mass. Besides the macrophages of the host, a number of tumor cells do also phagocyte silica crystals, leading to destruction of all those cells. The authors are of the opinion that the local modifications provoked by silica, could have interfered in the adaptation of the tumor with its nutrient stroma. Of these modifications, the stroma sclerosis seems to be the most effective in the inhibition of tumor growth. Some correlations were suggested between the here described results and those obtained by other workers who have used other inflammatory agents of different nature."} {"id": "PMID:179494", "title": "Dilute ethyl alcohol: effect on the sciatic nerve of the mouse.", "content": "The histological changes produced in peripheral nerve by topical ethyl alcohol have been infrequently studied in spite of widespread use of this neurotoxic agent in the management of pain and spasticity. In the present study the sciatic nerves of a series of albino mice were exposed to ethanol in concentrations of from 10% to 50% for from 15 to 60 seconds. An immediate physiochemical reaction took place, resulting in splitting of myelin sheaths and swelling of cellular organelles and cytoplasm. Nerves subsequently underwent Wallerian degeneration. A central core of fibers appeared to be normal. The longer exposure times or higher alcohol concentrations increased the extent to which the peripheral rim of altered tissue extended centrally into the nerve. Within altered tissue, all fiber types and sizes were found to be affected to an equal degree. To study the physical properties of alcohol in solution, absolute alcohol was slowly placed at the bottom of a cylinder filled with artificial or normal human spinal fluid and sequential levels of the solution were sampled 30 and 60 seconds after injection. Though hypobaric, alcohol dispersed rapidly so that specimens taken from the bottom of the cylinder were 65% as concentrated as specimens taken from the surface.", "contents": "Dilute ethyl alcohol: effect on the sciatic nerve of the mouse. The histological changes produced in peripheral nerve by topical ethyl alcohol have been infrequently studied in spite of widespread use of this neurotoxic agent in the management of pain and spasticity. In the present study the sciatic nerves of a series of albino mice were exposed to ethanol in concentrations of from 10% to 50% for from 15 to 60 seconds. An immediate physiochemical reaction took place, resulting in splitting of myelin sheaths and swelling of cellular organelles and cytoplasm. Nerves subsequently underwent Wallerian degeneration. A central core of fibers appeared to be normal. The longer exposure times or higher alcohol concentrations increased the extent to which the peripheral rim of altered tissue extended centrally into the nerve. Within altered tissue, all fiber types and sizes were found to be affected to an equal degree. To study the physical properties of alcohol in solution, absolute alcohol was slowly placed at the bottom of a cylinder filled with artificial or normal human spinal fluid and sequential levels of the solution were sampled 30 and 60 seconds after injection. Though hypobaric, alcohol dispersed rapidly so that specimens taken from the bottom of the cylinder were 65% as concentrated as specimens taken from the surface."} {"id": "PMID:179495", "title": "Neuropathy in the upper extremity after open-heart surgery.", "content": "Eleven patients with upper-extremity neurological abnormalities underwent open-heart surgery performed through a median sternotomy incision. Seven of the 11 patients were referred in the routine manner to evaluate and treat the neurological problem. The remaining four were part of a consecutively studied group of 11 patients examined prospectively to determine the possible presence of abnormalities. Two of these four patients were asymptomatic. All lesions could be postulated to occur within the brachial plexus, the most common area being the median cord, but lesions were also noted in the posterior and lateral cords and upper trunk. The etiology of the problem appears to be stretching injury of the brachial plexus from retraction of the sternum, which in turn causes retroclavicular displacement of the clavicle. However, it is possible that an ischemic neuropathy could result from intraarterial procedures in some of our patients. The possibility that neurologic deficit may occur in the upper extremity should be considered by physicians who may have the opportunity to evaluate patients who undergo open-heart surgery.", "contents": "Neuropathy in the upper extremity after open-heart surgery. Eleven patients with upper-extremity neurological abnormalities underwent open-heart surgery performed through a median sternotomy incision. Seven of the 11 patients were referred in the routine manner to evaluate and treat the neurological problem. The remaining four were part of a consecutively studied group of 11 patients examined prospectively to determine the possible presence of abnormalities. Two of these four patients were asymptomatic. All lesions could be postulated to occur within the brachial plexus, the most common area being the median cord, but lesions were also noted in the posterior and lateral cords and upper trunk. The etiology of the problem appears to be stretching injury of the brachial plexus from retraction of the sternum, which in turn causes retroclavicular displacement of the clavicle. However, it is possible that an ischemic neuropathy could result from intraarterial procedures in some of our patients. The possibility that neurologic deficit may occur in the upper extremity should be considered by physicians who may have the opportunity to evaluate patients who undergo open-heart surgery."} {"id": "PMID:179497", "title": "Clinical, virological, and pathological features of herpesvirus SA8 infection in conventional and gnotobiotic infant baboons (Papio cynocephalus).", "content": "The pathogenicity of a strain of simian herpesvirus SA8 in one month old conventional and gnotobiotic baboons was investigated. Intratracheal inoculation resulted in a mortality rate of 1/5 in the conventional and 1/4 in the gnotobiotic group. Disease became apparent after 3 days and was characterized by respiratory distress, reduced formula intake, weight loss and fever in both groups. Isolation of herpesvirus from the respiratory tract, lymphoid organs, kidneys, adrenals, and CNS was more frequent by explant culturing than by routine procedures. Although there was a significant difference in total white blood counts (WBC), with higher values in conventional vs. gnotobiotic infants, the absolute number of lymphocytes was not different. The lower number of WBCs apparently was due to fewer polymorphonuclear leukocytes in the gnotobiotic baboons. Infection resulted in a leukopenia 5 days post infection (p.i.) and a leukocytosis 10 days p.i. in both groups. The animals, which succumbed, had acute necrotizing fibrinous pneumonia. Intranuclear inclusion bodies typical for herpesviruses were present. All the surviving infant baboons had subacute interstitial pneumonia, when sacrificed 35 days p.i.", "contents": "Clinical, virological, and pathological features of herpesvirus SA8 infection in conventional and gnotobiotic infant baboons (Papio cynocephalus). The pathogenicity of a strain of simian herpesvirus SA8 in one month old conventional and gnotobiotic baboons was investigated. Intratracheal inoculation resulted in a mortality rate of 1/5 in the conventional and 1/4 in the gnotobiotic group. Disease became apparent after 3 days and was characterized by respiratory distress, reduced formula intake, weight loss and fever in both groups. Isolation of herpesvirus from the respiratory tract, lymphoid organs, kidneys, adrenals, and CNS was more frequent by explant culturing than by routine procedures. Although there was a significant difference in total white blood counts (WBC), with higher values in conventional vs. gnotobiotic infants, the absolute number of lymphocytes was not different. The lower number of WBCs apparently was due to fewer polymorphonuclear leukocytes in the gnotobiotic baboons. Infection resulted in a leukopenia 5 days post infection (p.i.) and a leukocytosis 10 days p.i. in both groups. The animals, which succumbed, had acute necrotizing fibrinous pneumonia. Intranuclear inclusion bodies typical for herpesviruses were present. All the surviving infant baboons had subacute interstitial pneumonia, when sacrificed 35 days p.i."} {"id": "PMID:179498", "title": "Purification of virions and nucleocapsids of herpes simplex virus by means of metrizamide and sodium metrizoate gradients.", "content": "The generation of density gradients for ultracentrifuging by freezing and thawing was applied to formation of linear density gradients with sodium metrizoate and metrizamide. Using these gradient materials simple and rapid methods for purification of virions and nucleocapsids of herpes virus were elaborated. Using metrizamide the recovery of infectivity was 10-30 per cent, and the purification of virions measured as reduction of host protein was 1700 times. Using metrizoate, the recovery of nucleocapsids was 30-60 per cent and the purification from host DNA and protein was 900 and 1700 times, respectively.", "contents": "Purification of virions and nucleocapsids of herpes simplex virus by means of metrizamide and sodium metrizoate gradients. The generation of density gradients for ultracentrifuging by freezing and thawing was applied to formation of linear density gradients with sodium metrizoate and metrizamide. Using these gradient materials simple and rapid methods for purification of virions and nucleocapsids of herpes virus were elaborated. Using metrizamide the recovery of infectivity was 10-30 per cent, and the purification of virions measured as reduction of host protein was 1700 times. Using metrizoate, the recovery of nucleocapsids was 30-60 per cent and the purification from host DNA and protein was 900 and 1700 times, respectively."} {"id": "PMID:179499", "title": "Correlation of persistent mouse hepatitis virus (MHV-3) infection with its effect on mouse macrophage cultures.", "content": "MHV 3 has three distinct effects in different strains of mice: strain A mice are completely resistant, most strains (including C57BL, DBA/2, BALB/c and NZB strains) die of acute hepatitis whereas in certain strains (eg. C3H and A2G) the virus produces a persistent infection with neurological symptoms. In cultures of peritoneal macrophages from susceptible strains, MHV-3 replicated freely, with giant cell formation. No replication was observed in macrophages from strain A mice. In contrast to this full susceptibility or resistance, macrophage cultures from strains of mice in which persistent infections occur showed an intermediate susceptibility, as judged by the intensity of the cytopathic effect, the presence of viral antigens in the cytoplasm and levels of viral replication. Possible ways in which the intermediate susceptibility of macrophages and persistent infections might be related are discussed.", "contents": "Correlation of persistent mouse hepatitis virus (MHV-3) infection with its effect on mouse macrophage cultures. MHV 3 has three distinct effects in different strains of mice: strain A mice are completely resistant, most strains (including C57BL, DBA/2, BALB/c and NZB strains) die of acute hepatitis whereas in certain strains (eg. C3H and A2G) the virus produces a persistent infection with neurological symptoms. In cultures of peritoneal macrophages from susceptible strains, MHV-3 replicated freely, with giant cell formation. No replication was observed in macrophages from strain A mice. In contrast to this full susceptibility or resistance, macrophage cultures from strains of mice in which persistent infections occur showed an intermediate susceptibility, as judged by the intensity of the cytopathic effect, the presence of viral antigens in the cytoplasm and levels of viral replication. Possible ways in which the intermediate susceptibility of macrophages and persistent infections might be related are discussed."} {"id": "PMID:179500", "title": "Persistent parainfluenza type 1 (6/94) infection of brain cells in tissue culture.", "content": "A state of persistent infection with parainfluenza type 1 virus (6/94 strain) was established in cultures of human and bovine brain cells. Following primary infection of human brain cells, viral cytopathic effect (CPE) and hemadsorption (HAD) depended on the multiplicity of infection. After persistent infection was established the virus rapidly became cell-associated; no CPE occurred and no viral antigen was detectable by HAD, immunofluorescence (FA), or immunoprecipitation. Infectious virus could be recovered only by fusion or cocultivation. This was in marked contrast with infected bovine brain cells, where, following primary infection, little or no CPE occurred. A productive infection rapidly evolved and persisted without CPE, but with 100 per cent HAD and FA positive cells.", "contents": "Persistent parainfluenza type 1 (6/94) infection of brain cells in tissue culture. A state of persistent infection with parainfluenza type 1 virus (6/94 strain) was established in cultures of human and bovine brain cells. Following primary infection of human brain cells, viral cytopathic effect (CPE) and hemadsorption (HAD) depended on the multiplicity of infection. After persistent infection was established the virus rapidly became cell-associated; no CPE occurred and no viral antigen was detectable by HAD, immunofluorescence (FA), or immunoprecipitation. Infectious virus could be recovered only by fusion or cocultivation. This was in marked contrast with infected bovine brain cells, where, following primary infection, little or no CPE occurred. A productive infection rapidly evolved and persisted without CPE, but with 100 per cent HAD and FA positive cells."} {"id": "PMID:179501", "title": "The immunoperoxidase technique for rapid human cytomegalovirus identification.", "content": "Sixteen cytomegalovirus (CMV) isolates from both ill and healthy patients were identified by the immunoperoxidase technique (IP). CMV detection was accomplished by direct examination of the primary isolate using either direct (DIP) or indirect immunoperoxidase (IIP) techniques. In thirteen of the isolates, confirmation of identification was achieved by indirect immunofluorescence (IFA) and by demonstration of herpes particles by electron microscopy (EM). Further, in four cases of non-CMV alterations in the tissue culture which might be confused with actual infection, the IP test was negative as were the confirmatory tests. The IIP is preferred over the DIP test since the latter shows a certain amount of background stain of uninfected cells. Tissue culture cells showing focal CMV cytopathic effect contained both nuclear and cytoplasmic inclusions stained by IP technique. Nonspecific staining was associated with cytoplasmic inclusion bodies. The IP technique can detect individual cell CMV infection at 24 hours when EM reveals only unenveloped viral particles. It is sensitive, specific, and allows direct identification of infected cells in the primary isolate in as little as 90 minutes. Furthermore, it can be performed in standard isolation tissue culture tubes, whereas IFA requires the transfer of the infected cells onto slides or the routine use of Leighton tubes.", "contents": "The immunoperoxidase technique for rapid human cytomegalovirus identification. Sixteen cytomegalovirus (CMV) isolates from both ill and healthy patients were identified by the immunoperoxidase technique (IP). CMV detection was accomplished by direct examination of the primary isolate using either direct (DIP) or indirect immunoperoxidase (IIP) techniques. In thirteen of the isolates, confirmation of identification was achieved by indirect immunofluorescence (IFA) and by demonstration of herpes particles by electron microscopy (EM). Further, in four cases of non-CMV alterations in the tissue culture which might be confused with actual infection, the IP test was negative as were the confirmatory tests. The IIP is preferred over the DIP test since the latter shows a certain amount of background stain of uninfected cells. Tissue culture cells showing focal CMV cytopathic effect contained both nuclear and cytoplasmic inclusions stained by IP technique. Nonspecific staining was associated with cytoplasmic inclusion bodies. The IP technique can detect individual cell CMV infection at 24 hours when EM reveals only unenveloped viral particles. It is sensitive, specific, and allows direct identification of infected cells in the primary isolate in as little as 90 minutes. Furthermore, it can be performed in standard isolation tissue culture tubes, whereas IFA requires the transfer of the infected cells onto slides or the routine use of Leighton tubes."} {"id": "PMID:179502", "title": "Detection of type-specific antibody to herpes simplex virus type 1 and 2 in human sera by complement-fixation tests.", "content": "Type-specific antigens for herpes simplex virus type 1 and 2 were prepared by rigorous absorption of cell extracts with heterotypic immune sera. Type-specificity was demonstrated by immunodiffusion and complement-fixation tests against immune sera prepared in rabbits. Specific type 1 complement-fixing reactivity was detected in eleven of fifteen sera from Roman Catholic nuns and in two convalescent sera from patients with recurrent herpes labialis; these sera had been previously shown to contain neutralising and complement-fixing antibody to herpes simplex virus. Three of the non-reacting sera contained low or absent levels of type-common complement-fixing reactivity and other contained no type-specific neutralising antibody. With the exception of three \"acute\" sera, specific type 2 complement-fixing reactivity was detected in every convalescent or interim serum obtained from patients with a virologically-proven history of type 2 herpes virus infection. It is suggested that complement-fixation testing using these absorbed type-specific antigens preparations may provide a convenient and rapid method for the identification of type-specific antibody in human sera.", "contents": "Detection of type-specific antibody to herpes simplex virus type 1 and 2 in human sera by complement-fixation tests. Type-specific antigens for herpes simplex virus type 1 and 2 were prepared by rigorous absorption of cell extracts with heterotypic immune sera. Type-specificity was demonstrated by immunodiffusion and complement-fixation tests against immune sera prepared in rabbits. Specific type 1 complement-fixing reactivity was detected in eleven of fifteen sera from Roman Catholic nuns and in two convalescent sera from patients with recurrent herpes labialis; these sera had been previously shown to contain neutralising and complement-fixing antibody to herpes simplex virus. Three of the non-reacting sera contained low or absent levels of type-common complement-fixing reactivity and other contained no type-specific neutralising antibody. With the exception of three \"acute\" sera, specific type 2 complement-fixing reactivity was detected in every convalescent or interim serum obtained from patients with a virologically-proven history of type 2 herpes virus infection. It is suggested that complement-fixation testing using these absorbed type-specific antigens preparations may provide a convenient and rapid method for the identification of type-specific antibody in human sera."} {"id": "PMID:179505", "title": "[Enzymochemical organization of aortic baroreceptors].", "content": "The topography of the activity of succinate dehydrogenase, cytochrome oxidase, monoaminoxidase and esterase was studied in the arc of the aorta of the monkey, dog, cat, rabbit, rat. It was established that terminal portions of baroreceptors were accumulators of the activity of enzymes of the succinoxidase system connected with the mitochondria of a nervous component of sensory endings and the activity of cholinesterase localized in the zone of terminal branches of the baroreceptors fibres in the underlying specialized tissue. The activity of monoaminoxidase was found in the cytoplasm of Schwann cells of the baroreceptor fibres. No specific esterase was revealed in the baroceptors of the aorta arc of the animals in question. The enzymic organization of the cat's aorta baroreceptors is different from that of the other animals.", "contents": "[Enzymochemical organization of aortic baroreceptors]. The topography of the activity of succinate dehydrogenase, cytochrome oxidase, monoaminoxidase and esterase was studied in the arc of the aorta of the monkey, dog, cat, rabbit, rat. It was established that terminal portions of baroreceptors were accumulators of the activity of enzymes of the succinoxidase system connected with the mitochondria of a nervous component of sensory endings and the activity of cholinesterase localized in the zone of terminal branches of the baroreceptors fibres in the underlying specialized tissue. The activity of monoaminoxidase was found in the cytoplasm of Schwann cells of the baroreceptor fibres. No specific esterase was revealed in the baroceptors of the aorta arc of the animals in question. The enzymic organization of the cat's aorta baroreceptors is different from that of the other animals."} {"id": "PMID:179507", "title": "[The morphology of lung cancer and background changes according to bronchoscopic biopsy findings].", "content": "Results of a pathohistological investigation of bronchoscopy bioptic specimens in 523 patients, including 422 patients with cancer of the lungs, 7--with benign tumours of the lungs, 83,--with chronic nonspecific afflictions, and 11--with pulmonary tuberculosis, are discussed. A histological diagnosis of bronchogenic cancer was established in 210 out of 422 observations. In central cancer positive results of bronchobiopsy (i. i. revealing of tumour) were obtained in 198 (52.1%) out of 380 cases, in peripheral cancer - in 12 (28.5%) out of 42 cases. Investigations of bronchobiopsy specimens made it possible to establish: epidermoid cancer in 123 (58.6%) cases, microcellular anaplastic cancer in 58 (27.6%) of cases, adenocarcinoma in 15 (7.1%) of cases, macrocellular cancer in 1 (0.5%) case. In 13 observations (6.2%) the histological type of cancer was not identified. The specific gravity of epidermoid cancer was consistently greater than in investigations of operation and section material. Analysis of the background changes in bronchobiopsies in which no tumour tissue was observed showed a substantially lower incidence (P less than 0.01) of atypical metaplasia of the bronchial epithelium in chronic nonspecific diseases than in the bronchogenic cancer.", "contents": "[The morphology of lung cancer and background changes according to bronchoscopic biopsy findings]. Results of a pathohistological investigation of bronchoscopy bioptic specimens in 523 patients, including 422 patients with cancer of the lungs, 7--with benign tumours of the lungs, 83,--with chronic nonspecific afflictions, and 11--with pulmonary tuberculosis, are discussed. A histological diagnosis of bronchogenic cancer was established in 210 out of 422 observations. In central cancer positive results of bronchobiopsy (i. i. revealing of tumour) were obtained in 198 (52.1%) out of 380 cases, in peripheral cancer - in 12 (28.5%) out of 42 cases. Investigations of bronchobiopsy specimens made it possible to establish: epidermoid cancer in 123 (58.6%) cases, microcellular anaplastic cancer in 58 (27.6%) of cases, adenocarcinoma in 15 (7.1%) of cases, macrocellular cancer in 1 (0.5%) case. In 13 observations (6.2%) the histological type of cancer was not identified. The specific gravity of epidermoid cancer was consistently greater than in investigations of operation and section material. Analysis of the background changes in bronchobiopsies in which no tumour tissue was observed showed a substantially lower incidence (P less than 0.01) of atypical metaplasia of the bronchial epithelium in chronic nonspecific diseases than in the bronchogenic cancer."} {"id": "PMID:179508", "title": "[A case of cytomegalic disease of the newborn].", "content": "A generalized form of cytomegalic disease in newborns is relatively rare. According to the author's data, only one case of cytomegalia was observed during post-mortem investigations of 1724 newborns and young children. This was a full-term child which was born with jaundice, generalized petechial rash and hepatosplenomegaly. Histological investigations revealed cytomegalic cells in the lungs, liver, kidneys and parotid salivary glands; in the brain there was noted calcification of the walls of the lateral ventricles. In the stroma of organs lymphoid infiltration with proliferation of histiocytes was observed.", "contents": "[A case of cytomegalic disease of the newborn]. A generalized form of cytomegalic disease in newborns is relatively rare. According to the author's data, only one case of cytomegalia was observed during post-mortem investigations of 1724 newborns and young children. This was a full-term child which was born with jaundice, generalized petechial rash and hepatosplenomegaly. Histological investigations revealed cytomegalic cells in the lungs, liver, kidneys and parotid salivary glands; in the brain there was noted calcification of the walls of the lateral ventricles. In the stroma of organs lymphoid infiltration with proliferation of histiocytes was observed."} {"id": "PMID:179509", "title": "[Plasticity of the nervous system].", "content": "The most recent knowledge about the phenomenon of the nervous system plasticity are revised, as much in morphological as in physiological and molecular levels. The neuron morphological and physiological changes opposite to the experience are studied. The nervous system molecular adaptation to the information it receives as the base of all type of plasticity is also considered.", "contents": "[Plasticity of the nervous system]. The most recent knowledge about the phenomenon of the nervous system plasticity are revised, as much in morphological as in physiological and molecular levels. The neuron morphological and physiological changes opposite to the experience are studied. The nervous system molecular adaptation to the information it receives as the base of all type of plasticity is also considered."} {"id": "PMID:179510", "title": "[20 years later. Or, the long-term outcome of so-called mixed tumors of the lacrimal gland].", "content": "A report on two cases of long-term recurrence of mixed tumours of the lacrimal glands. The authors assess the problem of the protracted evolution of these tumours and their possible degeneration, and attempt to distinguish the degeneration which follows multiple recurrences of co-existing mixed carcinomatous tumours. They insist on the necessity in these cases of an initial wide neurosurgical exposure of the orbit, so as to perform the widest excision possible.", "contents": "[20 years later. Or, the long-term outcome of so-called mixed tumors of the lacrimal gland]. A report on two cases of long-term recurrence of mixed tumours of the lacrimal glands. The authors assess the problem of the protracted evolution of these tumours and their possible degeneration, and attempt to distinguish the degeneration which follows multiple recurrences of co-existing mixed carcinomatous tumours. They insist on the necessity in these cases of an initial wide neurosurgical exposure of the orbit, so as to perform the widest excision possible."} {"id": "PMID:179512", "title": "Intracranial and extracranial nasopharyngeal angiofibroma. A surgical approach.", "content": "Two patients with juvenile nasopharyngeal angiofibromas with known or suspected intracranial extension were treated successfully with a surgical procedure. The procedure involves careful preoperative examination with four-vessel carotid angiography followed by preoperative occlusion of the extracranial major feeding vessels. This is followed by craniotomy, direct control of all intracranial feeding vessels, and then total extirpation of the tumor.", "contents": "Intracranial and extracranial nasopharyngeal angiofibroma. A surgical approach. Two patients with juvenile nasopharyngeal angiofibromas with known or suspected intracranial extension were treated successfully with a surgical procedure. The procedure involves careful preoperative examination with four-vessel carotid angiography followed by preoperative occlusion of the extracranial major feeding vessels. This is followed by craniotomy, direct control of all intracranial feeding vessels, and then total extirpation of the tumor."} {"id": "PMID:179514", "title": "Multipotent lipotropic hormones. In search of a pituitary cell producing multipotent LPH.", "content": "The affinity for antiserum to the multipotent lipotropic hormone (beta-LPH) was tested by immunohistochemical staining of all known cell types in normal and certain abnormal mouse, rat, and human pituitaries. Results indicate that beta-LPH has ACTH, MSH, LH and StH(GH) immunologically cross-reacting determinants. Affinities of anti-LPH for TtH and MtH (prolactin) were not detected in normal pituitaries, but thyrotropic tumor cells reacted with anti-LPH. Absorption experiments confirm that the single polypeptide hormone of the pituitary, beta-LPH, is coded for ACTH and MSH activities. The multi-functional hormone, LPH probably is secreted by the adrenotropes. In addition to ACTH and MSH, it probably contains other antigenic and biologic determinants. Some of these may accentuate its lipotropic activities; others may be incidental. These are points calling for further correlated structural, biologic, and immunologic investigations.", "contents": "Multipotent lipotropic hormones. In search of a pituitary cell producing multipotent LPH. The affinity for antiserum to the multipotent lipotropic hormone (beta-LPH) was tested by immunohistochemical staining of all known cell types in normal and certain abnormal mouse, rat, and human pituitaries. Results indicate that beta-LPH has ACTH, MSH, LH and StH(GH) immunologically cross-reacting determinants. Affinities of anti-LPH for TtH and MtH (prolactin) were not detected in normal pituitaries, but thyrotropic tumor cells reacted with anti-LPH. Absorption experiments confirm that the single polypeptide hormone of the pituitary, beta-LPH, is coded for ACTH and MSH activities. The multi-functional hormone, LPH probably is secreted by the adrenotropes. In addition to ACTH and MSH, it probably contains other antigenic and biologic determinants. Some of these may accentuate its lipotropic activities; others may be incidental. These are points calling for further correlated structural, biologic, and immunologic investigations."} {"id": "PMID:179515", "title": "Cholangiocarcinoma arising in congenital hepatic fibrosis. A case report.", "content": "Congenital hepatic fibrosis (CHF) is a morphologic entity characterized by (1) abnormal fibrous septation, (2) preservation of the basic lobular architecture, and (3) hyperplasia and dilatation of bile ductules. Congenital hepatic fibrosis may present as a cause of portal hypertension in adolescents, in young adults, and, rarely, in older adults. It is this form of the disorder that has been emphasized in the literature. However, CHF may also be seen in association with the infantile polycystic kidney syndrome. In the latter, the hepatic disorder is usually clinically silent. Cholangiocarcinoma is a rare complication of comgenital hepatic fibrosis, with only two previously documented cases reported, to our knowledge. We report a third case and suggest that CHF may represent a dysplastic hamartoma that, with prolonged survival, may eventuate in the development of intrahepatic biliary neoplasia.", "contents": "Cholangiocarcinoma arising in congenital hepatic fibrosis. A case report. Congenital hepatic fibrosis (CHF) is a morphologic entity characterized by (1) abnormal fibrous septation, (2) preservation of the basic lobular architecture, and (3) hyperplasia and dilatation of bile ductules. Congenital hepatic fibrosis may present as a cause of portal hypertension in adolescents, in young adults, and, rarely, in older adults. It is this form of the disorder that has been emphasized in the literature. However, CHF may also be seen in association with the infantile polycystic kidney syndrome. In the latter, the hepatic disorder is usually clinically silent. Cholangiocarcinoma is a rare complication of comgenital hepatic fibrosis, with only two previously documented cases reported, to our knowledge. We report a third case and suggest that CHF may represent a dysplastic hamartoma that, with prolonged survival, may eventuate in the development of intrahepatic biliary neoplasia."} {"id": "PMID:179516", "title": "Intracytoplasmic lumina in breast carcinoma: a helpful histopathologic feature.", "content": "Eelectron microscopy has disclosed the presence of intracytoplasmic lumina within breast cancer cells. These structures can be recognized with the light microscope by their sharp, round outlines and thick walls. Their identification in large numbers may provide additional support for the breast origin of a metastatic tumor. Three illustrative cases in which demonstration of intracytoplasmic lumina was diagnostically helpful are presented.", "contents": "Intracytoplasmic lumina in breast carcinoma: a helpful histopathologic feature. Eelectron microscopy has disclosed the presence of intracytoplasmic lumina within breast cancer cells. These structures can be recognized with the light microscope by their sharp, round outlines and thick walls. Their identification in large numbers may provide additional support for the breast origin of a metastatic tumor. Three illustrative cases in which demonstration of intracytoplasmic lumina was diagnostically helpful are presented."} {"id": "PMID:179517", "title": "Melanotic neuroectodermal tumour of infancy: report of a case.", "content": "A case of melanotic neuroectodermal tumour occurring in a seven-month-old male infant is reported. The aetiopathogenesis, clinical features, treatment and prognosis of the condition are discussed. Tumours of the jaw in infancy are extremely rare, and pigmented tumours still rarer. One such case of pigmented tumour of the maxilla is the subject of this report.", "contents": "Melanotic neuroectodermal tumour of infancy: report of a case. A case of melanotic neuroectodermal tumour occurring in a seven-month-old male infant is reported. The aetiopathogenesis, clinical features, treatment and prognosis of the condition are discussed. Tumours of the jaw in infancy are extremely rare, and pigmented tumours still rarer. One such case of pigmented tumour of the maxilla is the subject of this report."} {"id": "PMID:179518", "title": "Sleep monitoring: the second manned Skylab mission.", "content": "The first objective measurements of man's ability to obtain adequate sleep during prolonged space flight were made during the three manned Skylab missions. EEG, EOG, and head-motion signals were acquired during sleep by use of an elastic recording cap containing sponge electrodes and an attached miniature preamplifier/accelerometer unit. A control-panel assembly, mounted in the sleep compartment, tested electrodes, preserved analog signals, and automatically analyzed data in real time (providing a telementered indication of sleep stage). One subject was studied during each manned mission and, while there was considerable variation among individuals, several characteristics were common to all three: stage 3 sleep increased during the flight and decreased in the postflight period; stage 4 was consistently decreased postflight, although this stage was variable during the flight; stage REM (rapid eye movement) was elevated, and REM latency decreased in the late postflight period (after day 3 postrecovery); and the number of awakenings during sleep either showed no change or decreased during the flight. In only the 28-d mission (Skylab 2) was there a significant decrease in total sleep time; in that case it was a result of voluntarily reduced rest time and was not due to difficulty in sleeping nor frequent awakening. The subject on the 84-d mission (Skylab 4) experienced more difficulty in the first half of the flight, showing a decreased total sleep time and increased sleep latency, but this resolved itself with time. Sleep latency presented no problem in the other flights. While many of the findings are statistically significant, in no case would they be expected to produce a noticeable decrement of performance capability. These findings suggest that men are able to obtain adequate sleep in regularly scheduled 8-h rest periods during extended space flights. It seems likely, based upon these results, that the problems encountered in earlier space flights did not arise from the zero-g environment per se but possibly were a result of more restricted living and working areas in the pre-Skylab spacecraft.", "contents": "Sleep monitoring: the second manned Skylab mission. The first objective measurements of man's ability to obtain adequate sleep during prolonged space flight were made during the three manned Skylab missions. EEG, EOG, and head-motion signals were acquired during sleep by use of an elastic recording cap containing sponge electrodes and an attached miniature preamplifier/accelerometer unit. A control-panel assembly, mounted in the sleep compartment, tested electrodes, preserved analog signals, and automatically analyzed data in real time (providing a telementered indication of sleep stage). One subject was studied during each manned mission and, while there was considerable variation among individuals, several characteristics were common to all three: stage 3 sleep increased during the flight and decreased in the postflight period; stage 4 was consistently decreased postflight, although this stage was variable during the flight; stage REM (rapid eye movement) was elevated, and REM latency decreased in the late postflight period (after day 3 postrecovery); and the number of awakenings during sleep either showed no change or decreased during the flight. In only the 28-d mission (Skylab 2) was there a significant decrease in total sleep time; in that case it was a result of voluntarily reduced rest time and was not due to difficulty in sleeping nor frequent awakening. The subject on the 84-d mission (Skylab 4) experienced more difficulty in the first half of the flight, showing a decreased total sleep time and increased sleep latency, but this resolved itself with time. Sleep latency presented no problem in the other flights. While many of the findings are statistically significant, in no case would they be expected to produce a noticeable decrement of performance capability. These findings suggest that men are able to obtain adequate sleep in regularly scheduled 8-h rest periods during extended space flights. It seems likely, based upon these results, that the problems encountered in earlier space flights did not arise from the zero-g environment per se but possibly were a result of more restricted living and working areas in the pre-Skylab spacecraft."} {"id": "PMID:179519", "title": "Metabolic and endocrine studies: the second manned Skylab mission.", "content": "This study conducted on the crewmembers of Skylab 3 was designed to evaluate the endocrinological adaption resulting from extend exposure to a space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters. The three men served as their own controls and were on a constant dietary intake. Complete metabolic collections were performed beginning 21 d before the flight, continuing throughout the flight, for 18 d postflight. Changes in fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone, vasopressin, and fluid compartments. Inter-individual variability was demonstrated in most experimental indices measured; however, statistically significant patterns have emerged which include: decreases in body weight and ADH, increases in plasma renin activity, and elevations in urinary catecholamines, aldosterone and cortisol concentrations. Urinary sodium was increased in flight but potassium was only slightly changed. Total body exchangeable K was slightly decreased in all three of the crewmen. Total body water and extracellular fluid were decreased postflight in almost all cases. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transiton to the zero gravity environment is interpretated as a true volume expasion resulting in a net fluid loss. This, in association with other factors, ultimately results in a reduction in intravascular volume leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewemn are considered to be essentially adapted to the space environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals.", "contents": "Metabolic and endocrine studies: the second manned Skylab mission. This study conducted on the crewmembers of Skylab 3 was designed to evaluate the endocrinological adaption resulting from extend exposure to a space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters. The three men served as their own controls and were on a constant dietary intake. Complete metabolic collections were performed beginning 21 d before the flight, continuing throughout the flight, for 18 d postflight. Changes in fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone, vasopressin, and fluid compartments. Inter-individual variability was demonstrated in most experimental indices measured; however, statistically significant patterns have emerged which include: decreases in body weight and ADH, increases in plasma renin activity, and elevations in urinary catecholamines, aldosterone and cortisol concentrations. Urinary sodium was increased in flight but potassium was only slightly changed. Total body exchangeable K was slightly decreased in all three of the crewmen. Total body water and extracellular fluid were decreased postflight in almost all cases. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transiton to the zero gravity environment is interpretated as a true volume expasion resulting in a net fluid loss. This, in association with other factors, ultimately results in a reduction in intravascular volume leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewemn are considered to be essentially adapted to the space environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals."} {"id": "PMID:179520", "title": "Ultrastructural effects of +Gz stress on swine cardiac muscle.", "content": "Miniature swine were subjected to 9 +Gz acceleration for 60-120s. Within 2 h following the +Gz force, the anterior papillary muscle was removed and prepared for scanning and electron microscopy. Ultrastructural changes observed in the cardiac myocytes included cellular redistribution of mitochondria and nuclei. Tears in the contractile fibers, bizarre profiles or nuclei, and peculiar membrane-bounded bodies in the cytoplasm also were observed. Hemorrhagic areas were localized around the Purkinje fibers. The T system and plasma membrane appeared unperturbed. The conclusion was drawn that, following high +Gz levels of acceleration, damage to myocardial ultrastructure ensues.", "contents": "Ultrastructural effects of +Gz stress on swine cardiac muscle. Miniature swine were subjected to 9 +Gz acceleration for 60-120s. Within 2 h following the +Gz force, the anterior papillary muscle was removed and prepared for scanning and electron microscopy. Ultrastructural changes observed in the cardiac myocytes included cellular redistribution of mitochondria and nuclei. Tears in the contractile fibers, bizarre profiles or nuclei, and peculiar membrane-bounded bodies in the cytoplasm also were observed. Hemorrhagic areas were localized around the Purkinje fibers. The T system and plasma membrane appeared unperturbed. The conclusion was drawn that, following high +Gz levels of acceleration, damage to myocardial ultrastructure ensues."} {"id": "PMID:179521", "title": "Heat and simulated high altitude: effects on biochemical indices of stress and performance.", "content": "Five healthy, military test volunteers were alternately exposed on separate days to sea level, control conditions (22-23 degrees C, 40-50% RH), a hot wet environment (35 degrees C, 90% RH) or stimulated high altitude (4300 m, 22-23 degrees C, 20-30% RH) while carrying out assigned performance tasks. Acute exposure of 7 h to environmental heat consistently elicited significant increments in plasma levels of cortisol, dopamine-beta-hydroxylase, and uric acid while cholesterol and cyclic AMP levels were unaffected. Alternatively, exposure to altitude for the same duration failed to effect significant alterations in any of the aforementioned biochemical factors. Although both environmental stresses caused similar performance decrements, the responses of biochemical indices of stress were consistently related to the environment itself.", "contents": "Heat and simulated high altitude: effects on biochemical indices of stress and performance. Five healthy, military test volunteers were alternately exposed on separate days to sea level, control conditions (22-23 degrees C, 40-50% RH), a hot wet environment (35 degrees C, 90% RH) or stimulated high altitude (4300 m, 22-23 degrees C, 20-30% RH) while carrying out assigned performance tasks. Acute exposure of 7 h to environmental heat consistently elicited significant increments in plasma levels of cortisol, dopamine-beta-hydroxylase, and uric acid while cholesterol and cyclic AMP levels were unaffected. Alternatively, exposure to altitude for the same duration failed to effect significant alterations in any of the aforementioned biochemical factors. Although both environmental stresses caused similar performance decrements, the responses of biochemical indices of stress were consistently related to the environment itself."} {"id": "PMID:179522", "title": "Electron microscopical and enzyme histochemical changes in the rat myocardium during prolonged autolysis.", "content": "The effect on rat myocardium of autolysis at 19 degrees C, for up to 20 days, was studied by electron microscopy and enzyme histochemistry. The enzymes studied included monoamine oxidase (MAO), sytochrome oxidase (CytO), non-specific esterase ((Ns.E.), phosphorylase (P-ase), succinate dehydrogenase (SDH) and various NAD- and NADP-linked dehydrogenases. The myocardium lost its histochemical P-ase activity within a few hours of autolysis, whereas the activity of all other enzymes remained quite normal for at least about 4 days, except that of MAO and SDH, which were normal for about 8 and 12 days, respectively. The myocardial cells lost activity of various enzymes in a patchy manner during prolonged autolysis and practically all histochemical enzyme activity disappeared within 20 days. The early period of autolysis was accompanied by rapid ultrastructural changes of myocardial cells. During prolonged autolysis the gross architecture of the myocardium was lost gradually by the 12th to 20th days. Mitochondria were the organelles most resistant to the effects of autolysis, and numerous mitochondria with morphologically solid inner and outer membranes were seen among the totally disintegrated myocardium 20 days after death. The loss of P-ase activity coincided with the loss of glycogen. The loss of MAO, SDH and CytO activities was not closely related to the morphological preservation of mitochondria, but, in accordance with other enzymes, was more closely related to the disintegration of the over-all myocardial structure. The present results showed that the architecture of the myocardium, and especially that of the mitochondria, was surprisingly resistant to the effects of autolysis at room temperature. Also several enzymes of the myocardium other than those examined so far maintained quite stable histochemically demonstrable activity during prolonged autolysis. These observations give support to the possibility of making the diagnosis of myocardial infarction at postmortem more accurate than with the present morphological and histochemical routine methods.", "contents": "Electron microscopical and enzyme histochemical changes in the rat myocardium during prolonged autolysis. The effect on rat myocardium of autolysis at 19 degrees C, for up to 20 days, was studied by electron microscopy and enzyme histochemistry. The enzymes studied included monoamine oxidase (MAO), sytochrome oxidase (CytO), non-specific esterase ((Ns.E.), phosphorylase (P-ase), succinate dehydrogenase (SDH) and various NAD- and NADP-linked dehydrogenases. The myocardium lost its histochemical P-ase activity within a few hours of autolysis, whereas the activity of all other enzymes remained quite normal for at least about 4 days, except that of MAO and SDH, which were normal for about 8 and 12 days, respectively. The myocardial cells lost activity of various enzymes in a patchy manner during prolonged autolysis and practically all histochemical enzyme activity disappeared within 20 days. The early period of autolysis was accompanied by rapid ultrastructural changes of myocardial cells. During prolonged autolysis the gross architecture of the myocardium was lost gradually by the 12th to 20th days. Mitochondria were the organelles most resistant to the effects of autolysis, and numerous mitochondria with morphologically solid inner and outer membranes were seen among the totally disintegrated myocardium 20 days after death. The loss of P-ase activity coincided with the loss of glycogen. The loss of MAO, SDH and CytO activities was not closely related to the morphological preservation of mitochondria, but, in accordance with other enzymes, was more closely related to the disintegration of the over-all myocardial structure. The present results showed that the architecture of the myocardium, and especially that of the mitochondria, was surprisingly resistant to the effects of autolysis at room temperature. Also several enzymes of the myocardium other than those examined so far maintained quite stable histochemically demonstrable activity during prolonged autolysis. These observations give support to the possibility of making the diagnosis of myocardial infarction at postmortem more accurate than with the present morphological and histochemical routine methods."} {"id": "PMID:179523", "title": "[Needle biopsy in gout and pseudogout (author's transl)].", "content": "Radiological and morphological findings in advanced arthritis urica and pyrophosphate arthropathy are well known. In contrast, the early changes of synovial membrane in these disturbances of metabolism pose diagnostic problems. With the assistance of various cytological techniques and polarizing microscopical as well as electron microscopical investigation it was examined to what extent needle biopsies can be helpful in the differential diagnosis of gout and pseudogout. In 8 patients with gout and 11 patients with pseudogout synovial fluid and small tissue specimens could be obtained with the aid of the Parker-Pearson needle. Both fluid and tissue specimens were investigated light and electron microscopically. Cell counts were evaluated in a Rosenthal chamber. The differentiation of the cells in stained smears was done by counting 200-600 cells per case. Crystals were identified by polarizing microscopy in wet preparations of freshly aspirated synovial fluid. Polarizing microscopy of synovial fluid detected intra- as well as extracellular urate and pyrophosphate crystals. The wedge-shaped urate crystals and the larger partly polygonal pyrophosphate crystals showed different polarizing microscopical properties and a negative birefringence. The absolute cell counts in gout were higher than those in pseudogout. The relative cell counts of the different cell types in synovial fluid showed more variation in gout than in pseudogout. Cases with acute gout developed a relative leukocytosis in contrast to a relative lymphocytosis in chronic gout. A relative leukocytosis was constant in all patients with pseudogout. Sclerosed areas with scarce and plump villi as well as sometimes hyperplastic and polymorphous synovial cell layers could be demonstrated histologically in the tissue specimens of the needle biopsies in cases with gout. Urate crystals were less frequent in specimens fixed in formalin. The histological alterations in pseudogout were uniform, 2-4 rows of slightly pleomorphic synovial cells lined the inner surface of the joint capsule, sclerosing alterations were less frequent. Pyrophosphate crystals and calcified particles were seen within the synovial lining cells, the connective tissue and the enodthelial cells of the blood vessels in pseudogout specimens. Intra- as well as extracellular crystals could also be demonstrated with the aid of scanning electron microscopy in sediments of synovial fluid in gout and pseudogout. Transmission electron microscopical investigations of synovial tissue specimens detected proliferated and pleomorphic synovial lining cells in gout in contrast to a more monomorphic appearance of these cells in pseudogout. The crystals were washed out during the preparation techniques for transmission electron microscopy so that needle-like empty spaces resulted within cytoplasm of the phagocytic cells. These clefts were surrounded by phagosomal structures and densified cytoplasmic ground substance; sometimes they were also lined by membranes...", "contents": "[Needle biopsy in gout and pseudogout (author's transl)]. Radiological and morphological findings in advanced arthritis urica and pyrophosphate arthropathy are well known. In contrast, the early changes of synovial membrane in these disturbances of metabolism pose diagnostic problems. With the assistance of various cytological techniques and polarizing microscopical as well as electron microscopical investigation it was examined to what extent needle biopsies can be helpful in the differential diagnosis of gout and pseudogout. In 8 patients with gout and 11 patients with pseudogout synovial fluid and small tissue specimens could be obtained with the aid of the Parker-Pearson needle. Both fluid and tissue specimens were investigated light and electron microscopically. Cell counts were evaluated in a Rosenthal chamber. The differentiation of the cells in stained smears was done by counting 200-600 cells per case. Crystals were identified by polarizing microscopy in wet preparations of freshly aspirated synovial fluid. Polarizing microscopy of synovial fluid detected intra- as well as extracellular urate and pyrophosphate crystals. The wedge-shaped urate crystals and the larger partly polygonal pyrophosphate crystals showed different polarizing microscopical properties and a negative birefringence. The absolute cell counts in gout were higher than those in pseudogout. The relative cell counts of the different cell types in synovial fluid showed more variation in gout than in pseudogout. Cases with acute gout developed a relative leukocytosis in contrast to a relative lymphocytosis in chronic gout. A relative leukocytosis was constant in all patients with pseudogout. Sclerosed areas with scarce and plump villi as well as sometimes hyperplastic and polymorphous synovial cell layers could be demonstrated histologically in the tissue specimens of the needle biopsies in cases with gout. Urate crystals were less frequent in specimens fixed in formalin. The histological alterations in pseudogout were uniform, 2-4 rows of slightly pleomorphic synovial cells lined the inner surface of the joint capsule, sclerosing alterations were less frequent. Pyrophosphate crystals and calcified particles were seen within the synovial lining cells, the connective tissue and the enodthelial cells of the blood vessels in pseudogout specimens. Intra- as well as extracellular crystals could also be demonstrated with the aid of scanning electron microscopy in sediments of synovial fluid in gout and pseudogout. Transmission electron microscopical investigations of synovial tissue specimens detected proliferated and pleomorphic synovial lining cells in gout in contrast to a more monomorphic appearance of these cells in pseudogout. The crystals were washed out during the preparation techniques for transmission electron microscopy so that needle-like empty spaces resulted within cytoplasm of the phagocytic cells. These clefts were surrounded by phagosomal structures and densified cytoplasmic ground substance; sometimes they were also lined by membranes..."} {"id": "PMID:179524", "title": "Carbon-13 nuclear-magnetic-resonance spectroscopy of whole cells and of cytochrome C from Neurospora crass grown with (S-Me-13C)methionine.", "content": "Neurospora crassa cytochrome C biosynthetically labelled with [S-Me-13C]methionine was prepared and analysed by 13C nuclear-magnetic-resonance spectroscopy. The methyl group of methionine is extensively incorporated into an N-trimethyl-lysine-72 residue arise from S-adenosylmethionine transmethylation, and that the methyl carbons of methionine residues are sufficiently close to the haem centre to experience chemical shifts from the ring currents of the tetrapyrrole pi electrons and broadening due to binding of methionine-80 with the haem, as well as interaction of the S-E113C]methyl groups with the paramagnetic iron centre. Although whole cells of the labelled Neurospora produced a 13C resonance at the expected position for the methionyl methyl group most of the methyl label was diverted into N-tetra-alkyl ammonium compounds. After an active state of growth these labelled N-methyl compounds appear, in the main, to be low-molecular-weight derivatives of choline which, if associated with membrane, are in a sufficiently fluid environment to have short rotational correlation times. During a subsequent dormant growth period these compounds become associated to some extent with relatively more immobile phases as a result of membrane binding or an increase in membrane rigidity.", "contents": "Carbon-13 nuclear-magnetic-resonance spectroscopy of whole cells and of cytochrome C from Neurospora crass grown with (S-Me-13C)methionine. Neurospora crassa cytochrome C biosynthetically labelled with [S-Me-13C]methionine was prepared and analysed by 13C nuclear-magnetic-resonance spectroscopy. The methyl group of methionine is extensively incorporated into an N-trimethyl-lysine-72 residue arise from S-adenosylmethionine transmethylation, and that the methyl carbons of methionine residues are sufficiently close to the haem centre to experience chemical shifts from the ring currents of the tetrapyrrole pi electrons and broadening due to binding of methionine-80 with the haem, as well as interaction of the S-E113C]methyl groups with the paramagnetic iron centre. Although whole cells of the labelled Neurospora produced a 13C resonance at the expected position for the methionyl methyl group most of the methyl label was diverted into N-tetra-alkyl ammonium compounds. After an active state of growth these labelled N-methyl compounds appear, in the main, to be low-molecular-weight derivatives of choline which, if associated with membrane, are in a sufficiently fluid environment to have short rotational correlation times. During a subsequent dormant growth period these compounds become associated to some extent with relatively more immobile phases as a result of membrane binding or an increase in membrane rigidity."} {"id": "PMID:179525", "title": "Effects of sulphate-limited growth in continuous culture on the electron-transport chain and energy conservation in Escherichia coli K12.", "content": "Growth of Escherichia coli K12 in a chemostat was limited by sulphate concentrations lower than 300 muM. The synthesis of extracellular polysaccharide and a change in morphology accompanied sulphate-limited growth. Growth yields with respect to the amount of glycerol or oxygen consumed were sixfold and twofold lower respectively under these conditions than when growth was limited by glycerol. Sulphate-limited cells lacked the proton-translocating oxidoreduction segment of the electron-transport chain between NADH and the cytochromes, and particles prepared from these cells lacked the energy-dependent reduction of NAD+ by succinate, DL-alpha-glycerophosphate or D-lactate, suggesting the loss of site-I phosphorylation. Glycerol-limited cells contained cytochrome b556, b562 and o, ubiquinone and low concentrations of menaquinone. Sulphate limitation resulted in the additional synthesis of cytochromes d, a1, b558 and c550; the amount of ubiquinone was decreased and menaquinone was barely detectable. Non-haem iron and acid-labile sulphide concentrations were twofold lower in electron-transport particles prepared from sulphate-limited cells. Recovery of site-I phosphorylation could not be demonstrated after incubating sulphate-limited cells with or without glycerol, in either the absence or presence of added sulphate. The loss of site-I phosphorylation in sulphate-limited cells is discussed with reference to the accompanying alterations in cytochrome composition of such cells. Schemes are proposed for the functional organization of the respiratory chains of E. coli grown under conditions of glycerol or sulphate limitation.", "contents": "Effects of sulphate-limited growth in continuous culture on the electron-transport chain and energy conservation in Escherichia coli K12. Growth of Escherichia coli K12 in a chemostat was limited by sulphate concentrations lower than 300 muM. The synthesis of extracellular polysaccharide and a change in morphology accompanied sulphate-limited growth. Growth yields with respect to the amount of glycerol or oxygen consumed were sixfold and twofold lower respectively under these conditions than when growth was limited by glycerol. Sulphate-limited cells lacked the proton-translocating oxidoreduction segment of the electron-transport chain between NADH and the cytochromes, and particles prepared from these cells lacked the energy-dependent reduction of NAD+ by succinate, DL-alpha-glycerophosphate or D-lactate, suggesting the loss of site-I phosphorylation. Glycerol-limited cells contained cytochrome b556, b562 and o, ubiquinone and low concentrations of menaquinone. Sulphate limitation resulted in the additional synthesis of cytochromes d, a1, b558 and c550; the amount of ubiquinone was decreased and menaquinone was barely detectable. Non-haem iron and acid-labile sulphide concentrations were twofold lower in electron-transport particles prepared from sulphate-limited cells. Recovery of site-I phosphorylation could not be demonstrated after incubating sulphate-limited cells with or without glycerol, in either the absence or presence of added sulphate. The loss of site-I phosphorylation in sulphate-limited cells is discussed with reference to the accompanying alterations in cytochrome composition of such cells. Schemes are proposed for the functional organization of the respiratory chains of E. coli grown under conditions of glycerol or sulphate limitation."} {"id": "PMID:179526", "title": "Adenosine 3':5'-cyclic monophosphate-dependent protein kinase in brown fat from newborn rabbits. Changes in the binding of adenosine 3':5'-cyclic monophosphate after preincubation of the tissue with noradrenaline or incubation of the enzyme with adenosine triphosphate.", "content": "The equilibrium binding of cyclic AMP to a 150-fold purified preparation of protein kinase, when expressed as the reciprocal of bound against the reciprocal of free cyclic AMP, gave a plot consisting of two straight lines. The values of apparent Kb given by these lines were lowered by preincubating the intact tissue with noradrenaline or incubating the enzyme preparation with Mg2+ plus ATP. This effect was reversed by incubating the preparation (which contained some phosphatase impurities) with Mg2+ alone. None of these procedures affected the maximal binding of cyclic AMP. During incubation of the enzyme with Mg2+ plus ATP, the terminal phosphoryl group was incorporated into protein, over 40% being present in the kinase itself. This phosphate was removed during incubation of the preparation with Mg2+ alone. The validity of expressing cyclic AMP binding as a double-reciprocal plot is discussed, and the experimental plots are compared with those derived theoretically. The results suggest that protein kinase in brown fat is present in two forms, one with an apparent Kb for cyclic AMP or approx. 250 nM (dephosphorylation) and one with an apparent Kb of approx. 14 nM (phosphorylated). Preincubation of the tissue with noradrenaline results in phosphorylation of the kinase and an increase from 15 to 45% in the proportion of the higher-affinity form.", "contents": "Adenosine 3':5'-cyclic monophosphate-dependent protein kinase in brown fat from newborn rabbits. Changes in the binding of adenosine 3':5'-cyclic monophosphate after preincubation of the tissue with noradrenaline or incubation of the enzyme with adenosine triphosphate. The equilibrium binding of cyclic AMP to a 150-fold purified preparation of protein kinase, when expressed as the reciprocal of bound against the reciprocal of free cyclic AMP, gave a plot consisting of two straight lines. The values of apparent Kb given by these lines were lowered by preincubating the intact tissue with noradrenaline or incubating the enzyme preparation with Mg2+ plus ATP. This effect was reversed by incubating the preparation (which contained some phosphatase impurities) with Mg2+ alone. None of these procedures affected the maximal binding of cyclic AMP. During incubation of the enzyme with Mg2+ plus ATP, the terminal phosphoryl group was incorporated into protein, over 40% being present in the kinase itself. This phosphate was removed during incubation of the preparation with Mg2+ alone. The validity of expressing cyclic AMP binding as a double-reciprocal plot is discussed, and the experimental plots are compared with those derived theoretically. The results suggest that protein kinase in brown fat is present in two forms, one with an apparent Kb for cyclic AMP or approx. 250 nM (dephosphorylation) and one with an apparent Kb of approx. 14 nM (phosphorylated). Preincubation of the tissue with noradrenaline results in phosphorylation of the kinase and an increase from 15 to 45% in the proportion of the higher-affinity form."} {"id": "PMID:179528", "title": "The biosynthesis of alginic acid by Azotobacter vinelandii.", "content": "The sequence of reactions by which alginic acid is biosynthesized from sucrose in Azotobacter vinelandii was determined both by feeding radioactive individual enzymes involved. Results indicate that the first polymeric substance formed in the synthesis is polymannuronic acid and that mannuronic acid units are epimerized to guluronic acid at the polymer level. Guluronic acid does not appear to be formed at the monomer level, either free or in combination with GDP.", "contents": "The biosynthesis of alginic acid by Azotobacter vinelandii. The sequence of reactions by which alginic acid is biosynthesized from sucrose in Azotobacter vinelandii was determined both by feeding radioactive individual enzymes involved. Results indicate that the first polymeric substance formed in the synthesis is polymannuronic acid and that mannuronic acid units are epimerized to guluronic acid at the polymer level. Guluronic acid does not appear to be formed at the monomer level, either free or in combination with GDP."} {"id": "PMID:179527", "title": "Growth hormone, cyclic nucleotides and the rapid control of translation in heart muscle.", "content": "Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed.", "contents": "Growth hormone, cyclic nucleotides and the rapid control of translation in heart muscle. Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed."} {"id": "PMID:179529", "title": "The dexamethasone receptor in the Novikoff Hepatoma. Characterization and changes in concentration and nuclear uptake during glucocorticoid therapy.", "content": "Novikoff hepatoma ascites cells, grown intraperitoneally in rats, are shown to possess a high-affinity, low-capacity dexamethasone-binding protein. The receptor protein has an intracellular localization and concentration, association constant (Ka), glucocorticoid specificity and nuclear uptake in the presence of dexamethasone comparable with those of the G-protein of rat liver. During therapy of the tumour-bearing animal with cortisol, marked cyclic variations were observed in the concentration and nuclear uptake of the putative G-protein in the tumor cells; more transient variations were also observed in the Ka value of the receptor protein.", "contents": "The dexamethasone receptor in the Novikoff Hepatoma. Characterization and changes in concentration and nuclear uptake during glucocorticoid therapy. Novikoff hepatoma ascites cells, grown intraperitoneally in rats, are shown to possess a high-affinity, low-capacity dexamethasone-binding protein. The receptor protein has an intracellular localization and concentration, association constant (Ka), glucocorticoid specificity and nuclear uptake in the presence of dexamethasone comparable with those of the G-protein of rat liver. During therapy of the tumour-bearing animal with cortisol, marked cyclic variations were observed in the concentration and nuclear uptake of the putative G-protein in the tumor cells; more transient variations were also observed in the Ka value of the receptor protein."} {"id": "PMID:179530", "title": "Yeast phosphoglycerate mutate. Cyanogen bromide cleavage and amino acid sequence of an active-site peptide.", "content": "The molecular weight and amino acid composition of phosphoglycerate mutase from yeast were determined. CNBr cleavage produced a large (190-residue) fragment and a small (60-residue) fragment. Tryptic and chymotryptic peptides derived from the large fragment were fractionated by ion-exchange chromatography. Peptides from two histidine-containing regions were isolated and the amino acid sequences were determined. Correlation of these data with X-ray-crystallographic evidence shows that the histidine residue in the sequence Arg-Leu Asn-Glu-Arg-His-Tyr-Gly-Asp-Leu-Glu-Gly-Lys is located at the active site.", "contents": "Yeast phosphoglycerate mutate. Cyanogen bromide cleavage and amino acid sequence of an active-site peptide. The molecular weight and amino acid composition of phosphoglycerate mutase from yeast were determined. CNBr cleavage produced a large (190-residue) fragment and a small (60-residue) fragment. Tryptic and chymotryptic peptides derived from the large fragment were fractionated by ion-exchange chromatography. Peptides from two histidine-containing regions were isolated and the amino acid sequences were determined. Correlation of these data with X-ray-crystallographic evidence shows that the histidine residue in the sequence Arg-Leu Asn-Glu-Arg-His-Tyr-Gly-Asp-Leu-Glu-Gly-Lys is located at the active site."} {"id": "PMID:179531", "title": "Chemistry of the collagen cross-links. Nature of the cross-links in the polymorphic forms of dermal collagen during development.", "content": "Both the type I and type III collagens present in embryonic dermis are stabilized by the intermolecular cross-link, hydroxylysino-5-oxonorleucine, derived from hydroxylysine-aldehyde, although the type I collagen possesses a significant proportion of dehydrohydroxylysinonorleucine. However, concurrent with the change in the proportion of the two types of collagen during postnatal development there is a change-over with both type I and III collagens to the labile cross-link, dehydrohydroxylysinonorleucine, derived from lysine aldehyde. The results indicate that the change in the nature of the cross-link with development is determined primarily by the change in the extent of hydroxylation of the lysine residues in the terminal non-helical regions rather than being due to the change in the type of collagen.", "contents": "Chemistry of the collagen cross-links. Nature of the cross-links in the polymorphic forms of dermal collagen during development. Both the type I and type III collagens present in embryonic dermis are stabilized by the intermolecular cross-link, hydroxylysino-5-oxonorleucine, derived from hydroxylysine-aldehyde, although the type I collagen possesses a significant proportion of dehydrohydroxylysinonorleucine. However, concurrent with the change in the proportion of the two types of collagen during postnatal development there is a change-over with both type I and III collagens to the labile cross-link, dehydrohydroxylysinonorleucine, derived from lysine aldehyde. The results indicate that the change in the nature of the cross-link with development is determined primarily by the change in the extent of hydroxylation of the lysine residues in the terminal non-helical regions rather than being due to the change in the type of collagen."} {"id": "PMID:179532", "title": "Studies by electron-paramagnetic-resonance spectroscopy on the mechanism of action of xanthine dehydrogenase from Veillonella alcalescens.", "content": "E.p.r- (electron-paramagnetic-resonance) spectroscopy was used to compare chemical environment and reactivity of molybdenum, flavin and iron-sulphur centres in the enzyme xanthine dehydrogenase from Veillonella alcalescens (Micrococcus lactilyticus) with those of the corresponding centres in milk xanthine oxidase. The dehydrogenase is frequently contaminated with small but variable amounts of a species resistant to oxidation and giving a new molybdenum (V) e.p.r. signal, \"Resting I\". There is also a \"desulpho\" form of the enzyme giving a Slow Mo(V) signal, indistinguishable from that of the milk enzyme. Molybdenum of the active enzyme behaves in a manner analogous to that of the milk enzyme, giving a Rapid Mo(V) signal on partial reduction with substrates or dithionite. Detailed comparison shows that molybdenum in each enzyme must have the same ligand atoms arranged in the same manner. As with the milk enzyme, complex-formation between reduced dehydrogenase and purine substrate molecules, presumably interacting at the normal substrate-binding site, modifies the Rapid signal, confirming that such substrates interact near molybdenum. The dehydrogenase-flavin semiquinone signal is identical with that of the oxidase but, in contrast, there is only one iron-sulphur signal. The latter gives an e.p.r. spectrum similar to that of aldehyde oxidase.", "contents": "Studies by electron-paramagnetic-resonance spectroscopy on the mechanism of action of xanthine dehydrogenase from Veillonella alcalescens. E.p.r- (electron-paramagnetic-resonance) spectroscopy was used to compare chemical environment and reactivity of molybdenum, flavin and iron-sulphur centres in the enzyme xanthine dehydrogenase from Veillonella alcalescens (Micrococcus lactilyticus) with those of the corresponding centres in milk xanthine oxidase. The dehydrogenase is frequently contaminated with small but variable amounts of a species resistant to oxidation and giving a new molybdenum (V) e.p.r. signal, \"Resting I\". There is also a \"desulpho\" form of the enzyme giving a Slow Mo(V) signal, indistinguishable from that of the milk enzyme. Molybdenum of the active enzyme behaves in a manner analogous to that of the milk enzyme, giving a Rapid Mo(V) signal on partial reduction with substrates or dithionite. Detailed comparison shows that molybdenum in each enzyme must have the same ligand atoms arranged in the same manner. As with the milk enzyme, complex-formation between reduced dehydrogenase and purine substrate molecules, presumably interacting at the normal substrate-binding site, modifies the Rapid signal, confirming that such substrates interact near molybdenum. The dehydrogenase-flavin semiquinone signal is identical with that of the oxidase but, in contrast, there is only one iron-sulphur signal. The latter gives an e.p.r. spectrum similar to that of aldehyde oxidase."} {"id": "PMID:179533", "title": "Studies by electron-paramagnetic-resonance spectroscopy and stopped-flow spectrophotometry on the mechanism of action of turkey liver xanthine dehydrogenase.", "content": "Studies by e.p.r. (electron-paramagnetic-resonance) spectroscopy and by stopped-flow spectrophotometry on turkey liver xanthine dehydrogenase revealed strong similarities to as well as important differences from the Veillonella alcalescens xanthine dehydrogenase and milk xanthine oxidase. The turkey enzyme is contaminated by up to three non-functional forms, giving molybdenum e.p.r. signals designated Resting I, Resting II and Slow. Slow and to a lesser extent Resting I signals are like those from the Veillonella enzyme, whereas Resting II is very like a resting signal described by K. V. Rajagopolan, P. Handler, G. Palmer & H. Beinert (1968) (J. Biol. Chem. 243, 3784-3796) for aldehyde oxidase. Another non-functional form that gives the Inhibited signal is produced on treatment of the enzyme with formaldehyde. Stopped-flow measurements at 450 nm show that, as for the milk enzyme, reduction by xanthine is rate-limiting in enzyme turnover. The active enzyme gives rise to Very Rapid and Rapid molybdenum(V) e.p.r. signals, as well as to an FADH signal. That these signals are almost indistinguishable from those of the milk enzyme, confirms the similarities between the active sites. There are two types of iron-sulphur centres that give signals like those in the milk enzyme, though with slightly different parameters. Quantitative reduction titration of the functional enzyme with xanthine revealed two important differences between the turkey and the milk enzymes. First, the turkey enzyme FADH/FADH2 system has a redox potential sufficiently low that xanthine is incapable of reducing the flavin completely. This finding presumably explains the very low oxidase activity. Secondly, whereas the Fe/S II chromophore in the milk enzyme has a relatively high redox potential, for the turkey enzyme the value of this potential is lower and similar to that of its Fe/S I chromophore.", "contents": "Studies by electron-paramagnetic-resonance spectroscopy and stopped-flow spectrophotometry on the mechanism of action of turkey liver xanthine dehydrogenase. Studies by e.p.r. (electron-paramagnetic-resonance) spectroscopy and by stopped-flow spectrophotometry on turkey liver xanthine dehydrogenase revealed strong similarities to as well as important differences from the Veillonella alcalescens xanthine dehydrogenase and milk xanthine oxidase. The turkey enzyme is contaminated by up to three non-functional forms, giving molybdenum e.p.r. signals designated Resting I, Resting II and Slow. Slow and to a lesser extent Resting I signals are like those from the Veillonella enzyme, whereas Resting II is very like a resting signal described by K. V. Rajagopolan, P. Handler, G. Palmer & H. Beinert (1968) (J. Biol. Chem. 243, 3784-3796) for aldehyde oxidase. Another non-functional form that gives the Inhibited signal is produced on treatment of the enzyme with formaldehyde. Stopped-flow measurements at 450 nm show that, as for the milk enzyme, reduction by xanthine is rate-limiting in enzyme turnover. The active enzyme gives rise to Very Rapid and Rapid molybdenum(V) e.p.r. signals, as well as to an FADH signal. That these signals are almost indistinguishable from those of the milk enzyme, confirms the similarities between the active sites. There are two types of iron-sulphur centres that give signals like those in the milk enzyme, though with slightly different parameters. Quantitative reduction titration of the functional enzyme with xanthine revealed two important differences between the turkey and the milk enzymes. First, the turkey enzyme FADH/FADH2 system has a redox potential sufficiently low that xanthine is incapable of reducing the flavin completely. This finding presumably explains the very low oxidase activity. Secondly, whereas the Fe/S II chromophore in the milk enzyme has a relatively high redox potential, for the turkey enzyme the value of this potential is lower and similar to that of its Fe/S I chromophore."} {"id": "PMID:179534", "title": "Some properties of an alcohol dehydrogenase partially purified from baker's yeast grown without added zinc.", "content": "Alcohol dehydrogenase was partially purified from yeast (Saccharomyces cerevisiae) grown in the presence of 20 muM-MnSO4 without added Zn2+ and from yeast grown in the presence of 1.8 muM-MnSO4. The enzyme from yeast grown with added Zn2+ has the same properties as the crystalline enzyme from commercial supplies of baker's yeast. The enzyme from yeast grown without added An2+ has quite different properties. It has a mol.wt. in the region of 72000 and an S 20 w of 5.8S. The values can be compared with a mol.wt. of 141000 and an S 20 w of 7.6S for the crystalline enzyme. ADP-ribose, a common impurity in commercial samples of NAD+, is a potent competitive inhibitor of the new enzyme (K1 = 0.5 muM), but is not so for the crystalline enzyme. The observed maximum rate of ethanol oxidation at pH 7.05 and 25 degrees C was decreased 12-fold by the presence of 0.06 mol of inhibitor/mol of NAD+ when using the enzyme from Zn2+-deficient yeast, but with crystalline enzyme the maximum rate was essentially unchanged by this concentration of inhibitor. The kinetic characteristics for the two enzymes with ethanol, butan-1-ol, acetaldehyde and butyraldehyde as substrates are markedly different. These kinetic differences are discussed in relation to the mechanism of catalysis for the enzyme from Zn2+-deficient yeast.", "contents": "Some properties of an alcohol dehydrogenase partially purified from baker's yeast grown without added zinc. Alcohol dehydrogenase was partially purified from yeast (Saccharomyces cerevisiae) grown in the presence of 20 muM-MnSO4 without added Zn2+ and from yeast grown in the presence of 1.8 muM-MnSO4. The enzyme from yeast grown with added Zn2+ has the same properties as the crystalline enzyme from commercial supplies of baker's yeast. The enzyme from yeast grown without added An2+ has quite different properties. It has a mol.wt. in the region of 72000 and an S 20 w of 5.8S. The values can be compared with a mol.wt. of 141000 and an S 20 w of 7.6S for the crystalline enzyme. ADP-ribose, a common impurity in commercial samples of NAD+, is a potent competitive inhibitor of the new enzyme (K1 = 0.5 muM), but is not so for the crystalline enzyme. The observed maximum rate of ethanol oxidation at pH 7.05 and 25 degrees C was decreased 12-fold by the presence of 0.06 mol of inhibitor/mol of NAD+ when using the enzyme from Zn2+-deficient yeast, but with crystalline enzyme the maximum rate was essentially unchanged by this concentration of inhibitor. The kinetic characteristics for the two enzymes with ethanol, butan-1-ol, acetaldehyde and butyraldehyde as substrates are markedly different. These kinetic differences are discussed in relation to the mechanism of catalysis for the enzyme from Zn2+-deficient yeast."} {"id": "PMID:179535", "title": "The relationship between biological activity and primary structure of troponin I from white skeletal muscle of the rabbit.", "content": "1. A series of defined peptides which span the complete sequence were produced from troponin I isolated from white skeletal muscle of the rabbit. 2. Two peptides, CF1 (residues 64-133) and CN4 (residues 96-117) inhibited the Mg2+-stimulated adenosine triphosphatase of desensitized actomyosin. This inhibition was potentiated by tropomyosin and the Mg2+-stimulated adenosine triphosphatase of desensitized actomyosin. This inhibition, unlike that of troponin I and peptides derived from it, was not potentiated by tropomyosin. 4. The most active inhibitor, peptide CN4, was 45-75% as effective as troponin I when compared on a molar basis. The inhibitory peptide, CN4, and also whole troponin I were shown by affinity chromatography to interact specifically with actin. 5. A strong interaction with troponin C was demonstrated with peptide CF2 (residues 1-47), from the N-terminal region of troponin I. Somewhat weaker interactions were shown with peptides CN5 (residues 1-21) and with the inhibitory peptide CN4. 6. The significance of these interactions for the mechanisms of action of troponin I is discussed.", "contents": "The relationship between biological activity and primary structure of troponin I from white skeletal muscle of the rabbit. 1. A series of defined peptides which span the complete sequence were produced from troponin I isolated from white skeletal muscle of the rabbit. 2. Two peptides, CF1 (residues 64-133) and CN4 (residues 96-117) inhibited the Mg2+-stimulated adenosine triphosphatase of desensitized actomyosin. This inhibition was potentiated by tropomyosin and the Mg2+-stimulated adenosine triphosphatase of desensitized actomyosin. This inhibition, unlike that of troponin I and peptides derived from it, was not potentiated by tropomyosin. 4. The most active inhibitor, peptide CN4, was 45-75% as effective as troponin I when compared on a molar basis. The inhibitory peptide, CN4, and also whole troponin I were shown by affinity chromatography to interact specifically with actin. 5. A strong interaction with troponin C was demonstrated with peptide CF2 (residues 1-47), from the N-terminal region of troponin I. Somewhat weaker interactions were shown with peptides CN5 (residues 1-21) and with the inhibitory peptide CN4. 6. The significance of these interactions for the mechanisms of action of troponin I is discussed."} {"id": "PMID:179536", "title": "Study on sex-organ development. Oestrogen-receptor translocation in the developing chick M\u00fcllerian duct.", "content": "After oestradiol administration in vivo, 87-95% of the initial concentration of oestradiol receptor in the cytoplasm of the embryonic-chick M\u00fcllerian-duct cell was translocated into the nucleus. The process of translocation depends on the amount of oestardiol administered in vivo. At 6 h after oestradiol administration in vivo, about 30% replenishment of the initial content of the cytosol receptor was observed in the cytoplasm. The M\u00fcllerian-duct nuclei, after exposure to non-radioactive oestradiol, exhibit saturable exchange with [3H]oestradiol in vitro. The exchange of oestradiol is temperature- and time-dependent. The optimal temperature and time for exchange are 37-41 degrees C and 2h respectively. The [3H]oestradiol-receptor complex extracted from the exchanged nuclei is present in 5-6S form, and its isoelectric point is 6.8. The number of nuclear oestradiol-binding sites of the developing M\u00fcllerian duct are 1.66, 2.22, 2.63, and 2.50 pmol/mg of DNA respectively for embryos of 10, 12, 15 and 18 days. The dissociation constants of the nuclear oestradiol receptor of the four observed developmental stages range from 3.0 to 3.1 nM.", "contents": "Study on sex-organ development. Oestrogen-receptor translocation in the developing chick M\u00fcllerian duct. After oestradiol administration in vivo, 87-95% of the initial concentration of oestradiol receptor in the cytoplasm of the embryonic-chick M\u00fcllerian-duct cell was translocated into the nucleus. The process of translocation depends on the amount of oestardiol administered in vivo. At 6 h after oestradiol administration in vivo, about 30% replenishment of the initial content of the cytosol receptor was observed in the cytoplasm. The M\u00fcllerian-duct nuclei, after exposure to non-radioactive oestradiol, exhibit saturable exchange with [3H]oestradiol in vitro. The exchange of oestradiol is temperature- and time-dependent. The optimal temperature and time for exchange are 37-41 degrees C and 2h respectively. The [3H]oestradiol-receptor complex extracted from the exchanged nuclei is present in 5-6S form, and its isoelectric point is 6.8. The number of nuclear oestradiol-binding sites of the developing M\u00fcllerian duct are 1.66, 2.22, 2.63, and 2.50 pmol/mg of DNA respectively for embryos of 10, 12, 15 and 18 days. The dissociation constants of the nuclear oestradiol receptor of the four observed developmental stages range from 3.0 to 3.1 nM."} {"id": "PMID:179537", "title": "The incorporation of radioactive fatty acids and of radioactive derivatives of glucose into the phospholipids of subsynaptosomal fractions of cerebral cortex.", "content": "1. Crude synaptosomal fractions (P2) from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium containing labelled fatty acids and [3H]glucose. After the shortest incubation period (7.5 min) a high percentage (50-80%) of the total radioactive fatty acids was found in the P2 fractions. 2. After the incubation, the synaptosomal fractions were submitted to hypo-osmotic disruption and subsynaptosomal fractionation was carried out by using discontinuous-sucrose-gradient centrifugation. The specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomal preparation) and H (disrupted synaptosomes), as were the specific activities of a number of marker enzymes and the distribution of acetylcholine. 3. By using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose, the order to specific radioactivities in fraction D was found to be: phosphatidylinositol greater than phosphatidylcholine greater than phosphatidylserine greater than phosphatidylethanolamine. 4. The specific radioactivities of phosphatidylcholine and phosphatidylethanolamine were always higher in fraction D than in fraction E. As fraction E had higher specific activities of several membrane marker enzymes, the enhanced labelling found in fraction D was considered to be localized in the synaptic vesicles. In this fraction, phosphatidylinositol made particularly large contributions to the total phospholipid labelling derived from [14C]arachidonate and [3H]glucose. 5. The similar labelling ratios of fatty acid/glucose in the phospholipids of fractions D and E, and the high specific radioactivities in the total phospholipid of the soluble fraction O, suggested intrasynaptosomal phospholipid transport.", "contents": "The incorporation of radioactive fatty acids and of radioactive derivatives of glucose into the phospholipids of subsynaptosomal fractions of cerebral cortex. 1. Crude synaptosomal fractions (P2) from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium containing labelled fatty acids and [3H]glucose. After the shortest incubation period (7.5 min) a high percentage (50-80%) of the total radioactive fatty acids was found in the P2 fractions. 2. After the incubation, the synaptosomal fractions were submitted to hypo-osmotic disruption and subsynaptosomal fractionation was carried out by using discontinuous-sucrose-gradient centrifugation. The specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomal preparation) and H (disrupted synaptosomes), as were the specific activities of a number of marker enzymes and the distribution of acetylcholine. 3. By using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose, the order to specific radioactivities in fraction D was found to be: phosphatidylinositol greater than phosphatidylcholine greater than phosphatidylserine greater than phosphatidylethanolamine. 4. The specific radioactivities of phosphatidylcholine and phosphatidylethanolamine were always higher in fraction D than in fraction E. As fraction E had higher specific activities of several membrane marker enzymes, the enhanced labelling found in fraction D was considered to be localized in the synaptic vesicles. In this fraction, phosphatidylinositol made particularly large contributions to the total phospholipid labelling derived from [14C]arachidonate and [3H]glucose. 5. The similar labelling ratios of fatty acid/glucose in the phospholipids of fractions D and E, and the high specific radioactivities in the total phospholipid of the soluble fraction O, suggested intrasynaptosomal phospholipid transport."} {"id": "PMID:179557", "title": "[Protective effect of thymidine in relation to the cytostatic action of cyclic adenosine-3', 5'-monophosphate in mammalian cell cultures].", "content": "Under the action of lmM of cyclic adenosine-3',5'-monophosphate (cAMP) the survival and the rate of reproduction of the cells of Chinese hamster in the culture decreased in comparison with control to 27 and 42%, respectively. Addition of 0.02 mM thymidine together with cAMP almost completely eliminated the cytostatic action of the latter. Thymidine also prevented the cytostatic effect of noncyclic 5'-AMR, but failed to influence the death of the cells with the action of dibutyril cAMP and theophylline. Thymidine failed to prevent the inhibitory action of cAMP on the mutant strains of mouse cells defective by thymidinekinase. A conclusion was drawn that in the concentrations under study thecytostatic action of the exogenous cAMP on the cells of mammals served as the sequence of splitting to 5'-AMP in the culture medium and was realized by blocking one of the stages of TMP synthesis.", "contents": "[Protective effect of thymidine in relation to the cytostatic action of cyclic adenosine-3', 5'-monophosphate in mammalian cell cultures]. Under the action of lmM of cyclic adenosine-3',5'-monophosphate (cAMP) the survival and the rate of reproduction of the cells of Chinese hamster in the culture decreased in comparison with control to 27 and 42%, respectively. Addition of 0.02 mM thymidine together with cAMP almost completely eliminated the cytostatic action of the latter. Thymidine also prevented the cytostatic effect of noncyclic 5'-AMR, but failed to influence the death of the cells with the action of dibutyril cAMP and theophylline. Thymidine failed to prevent the inhibitory action of cAMP on the mutant strains of mouse cells defective by thymidinekinase. A conclusion was drawn that in the concentrations under study thecytostatic action of the exogenous cAMP on the cells of mammals served as the sequence of splitting to 5'-AMP in the culture medium and was realized by blocking one of the stages of TMP synthesis."} {"id": "PMID:179559", "title": "Echocardiographic pattern of right atrial tumour motion.", "content": "Propagation of Wilm's tumour to the right atrium was diagnosed by echocardiography. The tumour prolapsed into the right ventricle during each atrial systole. The presence of the tumour and its motion were confirmed by cardiac catheterization, cineangiography, and surgical exploration. Successful resection of the tumour was accomplished. Echocardiography was helpful in detecting the presence of the right atrial tumour and accurately reflected the pattern of its atrioventricular motion.", "contents": "Echocardiographic pattern of right atrial tumour motion. Propagation of Wilm's tumour to the right atrium was diagnosed by echocardiography. The tumour prolapsed into the right ventricle during each atrial systole. The presence of the tumour and its motion were confirmed by cardiac catheterization, cineangiography, and surgical exploration. Successful resection of the tumour was accomplished. Echocardiography was helpful in detecting the presence of the right atrial tumour and accurately reflected the pattern of its atrioventricular motion."} {"id": "PMID:179560", "title": "Comparison of tumour susceptibility among various organs of foetal, young and adult ICR/Jcl mice.", "content": "Urethane was found to be uniformly distributed in all the major organs of foetal, young and adult ICR/Jcl mice and then to disappear rapidly as measured by the incorporation of urethane-carbonyl-14C, thus permitting the accurate comparison of tumour susceptibility of cells in various organs of mice at different ages. Lung tumour frequency (tumours/lung) was significantly higher in mice treated with urethane when young (21 days old) and adult (63 days old) than in those treated in utero (Days 11-19 of gestation). When relative sensitivity of a lung cell was calculated as the ratio of average number of tumours per lung per mg of lung at the time of treatment, however, a lung cell of the foetus was more sensitive to urethane than that of the young and adult. Hepatomata were induced significantly only when male foetuses and neonates were exposed to urethane. The offspring exposed to urethane on Days 11-16, however, developed hepatomata in lower incidence than those exposed on Days 14-19, whereas the previous investigation by the author revealed that Days 11-13 correspond to the stage most sensitive to hepatocarcinogenesis. This contradiction was due to the occurrence of testicular hypogenesis (chemical castration) in all offspring of the former group. Differentiating female gonad and rapidly proliferating blood vessels of the placenta and deciduum were also sensitive to tumour induction by urethane. Thus, high tumour susceptibility of rapidly proliferating and undifferentiated cells suggests that some initiating events in the process of carcinogenesis may occur during or after DNA replication. Leukaemia induction in the young mice, but not in the foetus, remains to be elucidated.", "contents": "Comparison of tumour susceptibility among various organs of foetal, young and adult ICR/Jcl mice. Urethane was found to be uniformly distributed in all the major organs of foetal, young and adult ICR/Jcl mice and then to disappear rapidly as measured by the incorporation of urethane-carbonyl-14C, thus permitting the accurate comparison of tumour susceptibility of cells in various organs of mice at different ages. Lung tumour frequency (tumours/lung) was significantly higher in mice treated with urethane when young (21 days old) and adult (63 days old) than in those treated in utero (Days 11-19 of gestation). When relative sensitivity of a lung cell was calculated as the ratio of average number of tumours per lung per mg of lung at the time of treatment, however, a lung cell of the foetus was more sensitive to urethane than that of the young and adult. Hepatomata were induced significantly only when male foetuses and neonates were exposed to urethane. The offspring exposed to urethane on Days 11-16, however, developed hepatomata in lower incidence than those exposed on Days 14-19, whereas the previous investigation by the author revealed that Days 11-13 correspond to the stage most sensitive to hepatocarcinogenesis. This contradiction was due to the occurrence of testicular hypogenesis (chemical castration) in all offspring of the former group. Differentiating female gonad and rapidly proliferating blood vessels of the placenta and deciduum were also sensitive to tumour induction by urethane. Thus, high tumour susceptibility of rapidly proliferating and undifferentiated cells suggests that some initiating events in the process of carcinogenesis may occur during or after DNA replication. Leukaemia induction in the young mice, but not in the foetus, remains to be elucidated."} {"id": "PMID:179561", "title": "Accidental exposure to isocyanate fumes in a group of firemen.", "content": "A total of 35 firemen involved in fighting a fire in a factory in which polyurethane foam was made were exposed to fumes of toluene di-isocyanate from two large storage tanks which were damaged during the fire, resulting in massive spillage. Most of the men experienced symptoms during the fire or during the three weeks after it. The symptoms were mainly gastrointestinal, respiratory, or neurological. Altogether 15 men described gastrointestinal symptoms which subsided within two days of onset. Respiratory symptoms were described by 31 men and were most pronounced during the three days after the fire, thereafter tending to improve. The neurological findings are described separately. When the men were reviewed at six months there was a suggestion that some of them might have sustained long-term damage to the respiratory tract, and almost four years later 20 men had persistent respiratory symptoms. Serial measurements of ventilatory capacity revealed a marked decline in the first six months although this was not sustained.", "contents": "Accidental exposure to isocyanate fumes in a group of firemen. A total of 35 firemen involved in fighting a fire in a factory in which polyurethane foam was made were exposed to fumes of toluene di-isocyanate from two large storage tanks which were damaged during the fire, resulting in massive spillage. Most of the men experienced symptoms during the fire or during the three weeks after it. The symptoms were mainly gastrointestinal, respiratory, or neurological. Altogether 15 men described gastrointestinal symptoms which subsided within two days of onset. Respiratory symptoms were described by 31 men and were most pronounced during the three days after the fire, thereafter tending to improve. The neurological findings are described separately. When the men were reviewed at six months there was a suggestion that some of them might have sustained long-term damage to the respiratory tract, and almost four years later 20 men had persistent respiratory symptoms. Serial measurements of ventilatory capacity revealed a marked decline in the first six months although this was not sustained."} {"id": "PMID:179558", "title": "[New concepts on the etiopathogenesis of diarrhea].", "content": "The author discusses new knowledge concerning E. coli enterotoxins and Duovirus in the production of diarrheal disease.", "contents": "[New concepts on the etiopathogenesis of diarrhea]. The author discusses new knowledge concerning E. coli enterotoxins and Duovirus in the production of diarrheal disease."} {"id": "PMID:179562", "title": "Neurological complications after a single severe exposure to toluene di-isocyanate.", "content": "A total of 23 men complained of neurological symptoms after a single severe exposure to toluene di-isocyanate. Effects of exposure were immediate in five men and consisted of euphoria, ataxia, and loss of consciousness. These men and nine others complained of headache, difficulty in concentration, poor memory, and confusion during the next three weeks. Four years later it was found that nine further men had experienced symptoms that they had not been aware of at three weeks. In all, 13 men still complained of poor memory, personality change, irritability, or depression after four years. Psychometric testing showed a selective defect for relatively long-term recall in those with persistent symptoms at four years.", "contents": "Neurological complications after a single severe exposure to toluene di-isocyanate. A total of 23 men complained of neurological symptoms after a single severe exposure to toluene di-isocyanate. Effects of exposure were immediate in five men and consisted of euphoria, ataxia, and loss of consciousness. These men and nine others complained of headache, difficulty in concentration, poor memory, and confusion during the next three weeks. Four years later it was found that nine further men had experienced symptoms that they had not been aware of at three weeks. In all, 13 men still complained of poor memory, personality change, irritability, or depression after four years. Psychometric testing showed a selective defect for relatively long-term recall in those with persistent symptoms at four years."} {"id": "PMID:179563", "title": "Cooperativity and noncooperativity in the binding of NAD analogues to rabbit muscle glyceraldehyde-3-phosphate dehydrogenase.", "content": "Using NAD analogues as ligands, the structural requirements for negative cooperativity in binding to rabbit muscle glyceraldehyde-3-phosphate dehydrogenase were examined. Although the affinity of nicotinamide hypoxanthine dinucleotide is considerably lower than that of NAD+, it also binds to the enzyme with negative cooperatively. Two pairs of nicotinamide hypoxanthine dinucleotide binding sitess were distinguished, one pair having an affinity for the analogue which is 15 times that of the second pair. Negative cooperativity is also found in the Km values for the analogue. Thus modification of the adenine ring of NAD+ to hypoxanthine does not abolish negative cooperativity in coenzyme binding. Adenosine diphosphoribose binding to the same enzyme shows neither positive nor negative cooperativity, indicating that cooperativity apparently requires an intact nicotinamide ring in the coenzyme structure, under the conditions of these experiments. Occupancy of the nicotinamide subsite of the coenzyme binding site is not necessary for half-of-sites reactivity of alkylating or acylating compounds (Levitzki, A. (1974), J. Mol, Biol. 90, 451-458). However, it can be important in the negative cooperativity in ligand binding, as illustrated by adenosine diphosphoribose which fails to exhibit negative cooperativity. Occupancy of the adenine subsite by adenine is important for stabilization of the enzyme against thermal denaturation. Whether the stabilization is due to an altered conformation of the subunits or stabilization of the preexisting structure of the apoenzyme cannot be determined from these studies. However, nicotinamide hypoxanthine dinucleotide does not contribute to enzyme stability although it serves as a substrate and shows negative cooperativity.", "contents": "Cooperativity and noncooperativity in the binding of NAD analogues to rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. Using NAD analogues as ligands, the structural requirements for negative cooperativity in binding to rabbit muscle glyceraldehyde-3-phosphate dehydrogenase were examined. Although the affinity of nicotinamide hypoxanthine dinucleotide is considerably lower than that of NAD+, it also binds to the enzyme with negative cooperatively. Two pairs of nicotinamide hypoxanthine dinucleotide binding sitess were distinguished, one pair having an affinity for the analogue which is 15 times that of the second pair. Negative cooperativity is also found in the Km values for the analogue. Thus modification of the adenine ring of NAD+ to hypoxanthine does not abolish negative cooperativity in coenzyme binding. Adenosine diphosphoribose binding to the same enzyme shows neither positive nor negative cooperativity, indicating that cooperativity apparently requires an intact nicotinamide ring in the coenzyme structure, under the conditions of these experiments. Occupancy of the nicotinamide subsite of the coenzyme binding site is not necessary for half-of-sites reactivity of alkylating or acylating compounds (Levitzki, A. (1974), J. Mol, Biol. 90, 451-458). However, it can be important in the negative cooperativity in ligand binding, as illustrated by adenosine diphosphoribose which fails to exhibit negative cooperativity. Occupancy of the adenine subsite by adenine is important for stabilization of the enzyme against thermal denaturation. Whether the stabilization is due to an altered conformation of the subunits or stabilization of the preexisting structure of the apoenzyme cannot be determined from these studies. However, nicotinamide hypoxanthine dinucleotide does not contribute to enzyme stability although it serves as a substrate and shows negative cooperativity."} {"id": "PMID:179564", "title": "Regulation of a metabolic system in vitro: synthesis of threonine from aspartic acid.", "content": "Six enzymes involved in the conversion of aspartate to threonine have been extracted from Escherichia coli and separated from each other. Two of these enzymes, aspartokinase and homoserine dehydrogenase, have also been partially purified from Rhodopseudomonas spheroides. In an attempt to determine whether small changes in the kinetic properties of individual enzymes are important to the regulation of metabolic flux through a coupled reaction system, the partially purified enzymes were recombined in a variety of ways under reaction conditions designed to resemble the in vivo situation. These conditions include: use of an entire metabolic system rather than a single reaction; high enzyme concentrations at the same relative concentrations as found in the cell; and low, steady-state concentrations of substrates and products. Metabolic flux was followed spectrophotometrically and the concentrations of aspartic semialdehyde, hemoserine, O-phosphohomoserine, and threonine were measured. The results indicate that the threonine concentration is of major importance in regulating metabolic flux by inhibiting aspartokinase, the first reaction in threonine in the pathway. When threonine-insensitive aspartokinases were used, concentrations reached higher levels and the rate of NADPH oxidation remained higher. The fact that neither aspartic semialdehyde nor homoserine accumulated as the threonine concentration increased and the lack of correlation between changes in metabolic flux and ADP/ATP or NADPH/NADP ratios indicate that more subtle forms of metabolic regulation, such as \"reverse cascade\", secondary feedback sites, or \"energy charge\", are of little regulatory importance in this isolated, metabolic system. The results also emphasize the need for caution in projecting in vivo control mechanisms from in vitro experiments.", "contents": "Regulation of a metabolic system in vitro: synthesis of threonine from aspartic acid. Six enzymes involved in the conversion of aspartate to threonine have been extracted from Escherichia coli and separated from each other. Two of these enzymes, aspartokinase and homoserine dehydrogenase, have also been partially purified from Rhodopseudomonas spheroides. In an attempt to determine whether small changes in the kinetic properties of individual enzymes are important to the regulation of metabolic flux through a coupled reaction system, the partially purified enzymes were recombined in a variety of ways under reaction conditions designed to resemble the in vivo situation. These conditions include: use of an entire metabolic system rather than a single reaction; high enzyme concentrations at the same relative concentrations as found in the cell; and low, steady-state concentrations of substrates and products. Metabolic flux was followed spectrophotometrically and the concentrations of aspartic semialdehyde, hemoserine, O-phosphohomoserine, and threonine were measured. The results indicate that the threonine concentration is of major importance in regulating metabolic flux by inhibiting aspartokinase, the first reaction in threonine in the pathway. When threonine-insensitive aspartokinases were used, concentrations reached higher levels and the rate of NADPH oxidation remained higher. The fact that neither aspartic semialdehyde nor homoserine accumulated as the threonine concentration increased and the lack of correlation between changes in metabolic flux and ADP/ATP or NADPH/NADP ratios indicate that more subtle forms of metabolic regulation, such as \"reverse cascade\", secondary feedback sites, or \"energy charge\", are of little regulatory importance in this isolated, metabolic system. The results also emphasize the need for caution in projecting in vivo control mechanisms from in vitro experiments."} {"id": "PMID:179565", "title": "In vivo and in vitro phosphorylation of ribosomal proteins by protein kinases from Saccharomyces cerevisiae.", "content": "From the high salt wash of the ribosomes of the yeast Saccharomyces cerevisiae, three protein kinases have been isolated and separated by DEAE-cellulose chromatography. The three kinases differ in their abilities to phosphorylate substrates such as histones (calf thymus), casein, and S. cerevisiae ribosomes; two of the kinases showed increased activity in the presence of cyclic adenosine 3',5'-monophosphate when histones and 40S ribosomal subunits were used as substrates. The protein kinases catalyzed phosphorylation of certain proteins of the 40S and 60S ribosomal subunits, and 80S ribosomes in vitro. Nine proteins of the 80S ribosome, seven proteins of the 40S subunit, and eleven of the 60S subunit were phosphorylated; different proteins were modified to various extents when different kinases were used. We have identified several proteins of 40S and 60S ribosomal subunits which are not available to the kinases in the 80S particles. Ribosomes isolated from S. cerevisiae cells growing in logarithmic phase of growth were found to contain a number of phosphorylated proteins. Studies by two-dimensional polyacrylamide gel electrophoresis indicated that the ribosomal proteins phosphorylated in vivo correspond with those phosphorylated in vitro. The relationship of in vivo phsophorylation of ribosomes to the growth and physiology of S. cerevisiae is not known.", "contents": "In vivo and in vitro phosphorylation of ribosomal proteins by protein kinases from Saccharomyces cerevisiae. From the high salt wash of the ribosomes of the yeast Saccharomyces cerevisiae, three protein kinases have been isolated and separated by DEAE-cellulose chromatography. The three kinases differ in their abilities to phosphorylate substrates such as histones (calf thymus), casein, and S. cerevisiae ribosomes; two of the kinases showed increased activity in the presence of cyclic adenosine 3',5'-monophosphate when histones and 40S ribosomal subunits were used as substrates. The protein kinases catalyzed phosphorylation of certain proteins of the 40S and 60S ribosomal subunits, and 80S ribosomes in vitro. Nine proteins of the 80S ribosome, seven proteins of the 40S subunit, and eleven of the 60S subunit were phosphorylated; different proteins were modified to various extents when different kinases were used. We have identified several proteins of 40S and 60S ribosomal subunits which are not available to the kinases in the 80S particles. Ribosomes isolated from S. cerevisiae cells growing in logarithmic phase of growth were found to contain a number of phosphorylated proteins. Studies by two-dimensional polyacrylamide gel electrophoresis indicated that the ribosomal proteins phosphorylated in vivo correspond with those phosphorylated in vitro. The relationship of in vivo phsophorylation of ribosomes to the growth and physiology of S. cerevisiae is not known."} {"id": "PMID:179566", "title": "Association of methanol and ethanol with heme proteins.", "content": "The behavior of ferrihemoglobin and ferrimyoglobin in widely varying concentrations of the lowest four alcohols has been studied by optical and electron paramagnetic resonance absorption spectroscopy. Methanol and ethanol, at concentrations too low to cause general conformational destabilization of the protein, produce both optical and electron paramagnetic resonance absorption spectral changes in ferrihemoglobin. These changes arise from equilibrium associations, characterized by dissociation constants at 25 degrees C of about 40 and 200 mM, respectively, for the methanol-ferrihemoglobin and ethanol-ferrihemoglobin complexes so formed. Other optical spectral changes appear when the methanol concentration exceeds 3.5 M and the ethanol, 1.0 M. At concentrations lower than 0.5 M, 1- and 2-propanol produce spectral changes of this second kind. At room temperature no optical evidence has been found that the propanols associate with ferrihemoglobin in the manner of methanol and ethanol. Methanol and ethanol at low concentration have specific effects, characterized by electron paramagnetic resonance spectral differences, upon ferric alphaSH chains. All four alcohols, over a wide range of concentrations, reduce the symmetry of electron paramagnetic resonance spectra from frozen solutions of ferrihemoglobin; even at the high end of this concentration range, none of the alcohols reduces the symmetry of electron paramagnetic resonance spectra from frozen ferrimyoglobin. Ferrimyoglobin and catalase association with methanol is measurable optically; the binding is about five and sixty times weaker, respectively, for these two proteins as compared with ferrihemoglobin.", "contents": "Association of methanol and ethanol with heme proteins. The behavior of ferrihemoglobin and ferrimyoglobin in widely varying concentrations of the lowest four alcohols has been studied by optical and electron paramagnetic resonance absorption spectroscopy. Methanol and ethanol, at concentrations too low to cause general conformational destabilization of the protein, produce both optical and electron paramagnetic resonance absorption spectral changes in ferrihemoglobin. These changes arise from equilibrium associations, characterized by dissociation constants at 25 degrees C of about 40 and 200 mM, respectively, for the methanol-ferrihemoglobin and ethanol-ferrihemoglobin complexes so formed. Other optical spectral changes appear when the methanol concentration exceeds 3.5 M and the ethanol, 1.0 M. At concentrations lower than 0.5 M, 1- and 2-propanol produce spectral changes of this second kind. At room temperature no optical evidence has been found that the propanols associate with ferrihemoglobin in the manner of methanol and ethanol. Methanol and ethanol at low concentration have specific effects, characterized by electron paramagnetic resonance spectral differences, upon ferric alphaSH chains. All four alcohols, over a wide range of concentrations, reduce the symmetry of electron paramagnetic resonance spectra from frozen solutions of ferrihemoglobin; even at the high end of this concentration range, none of the alcohols reduces the symmetry of electron paramagnetic resonance spectra from frozen ferrimyoglobin. Ferrimyoglobin and catalase association with methanol is measurable optically; the binding is about five and sixty times weaker, respectively, for these two proteins as compared with ferrihemoglobin."} {"id": "PMID:179567", "title": "Effect of membrane protein on lipid bilayer structure: a spin-label electron spin resonance study of vesicular stomatitis virus.", "content": "Spin-label electron spin resonance (ESR) methods have been used to study the structure of the envelope of vesicular stomatitis virus (VSV). The data indicate that the lipid is organized in a bilayer structure. Proteolytic digestion of the glycoproteins which are the spike-like projections on the outer surface of the virus particle increases the fluidity of the lipid bilayer. Since the lipid composition of the virion reflects the composition of the host plasma membrane and the protein composition is determined by the viral genome, VSV was grown in both MDBK and BHK21-F cells to determine the effect of a change in lipid composition on the structure of the lipid bilayer of VSV. The lipid bilayer of the virion was found to be more rigid when derived from MDBK cells than from BHK21-F cells. Studies comparing spin-labeled intact cells and cell membrane fractions suggest that upon labeling the whole cell the spin label probes the plasma membrane. Comparison of spin-labeled VSV particles and their host cells indicates that the lipid bilayer of the plasma membrane is considerably more fluid than that of the virion. These results are discussed in terms of the effect of membrane-associated protein on the structure of the lipid bilayer.", "contents": "Effect of membrane protein on lipid bilayer structure: a spin-label electron spin resonance study of vesicular stomatitis virus. Spin-label electron spin resonance (ESR) methods have been used to study the structure of the envelope of vesicular stomatitis virus (VSV). The data indicate that the lipid is organized in a bilayer structure. Proteolytic digestion of the glycoproteins which are the spike-like projections on the outer surface of the virus particle increases the fluidity of the lipid bilayer. Since the lipid composition of the virion reflects the composition of the host plasma membrane and the protein composition is determined by the viral genome, VSV was grown in both MDBK and BHK21-F cells to determine the effect of a change in lipid composition on the structure of the lipid bilayer of VSV. The lipid bilayer of the virion was found to be more rigid when derived from MDBK cells than from BHK21-F cells. Studies comparing spin-labeled intact cells and cell membrane fractions suggest that upon labeling the whole cell the spin label probes the plasma membrane. Comparison of spin-labeled VSV particles and their host cells indicates that the lipid bilayer of the plasma membrane is considerably more fluid than that of the virion. These results are discussed in terms of the effect of membrane-associated protein on the structure of the lipid bilayer."} {"id": "PMID:179568", "title": "Sequence composition of the template-active fraction of rat liver chromatin.", "content": "Rat liver chromatin has been separated into nuclease-sensitive and -resistant fractions after mild digestion with DNAase II. The nuclease-sensitive material is further fractionated into Mg2+ -soluble and -insoluble chromatin fractions. The kinetics of production of these chromatin fractions have been investigated. After a brief enzyme treatment (5 min at 10 enzyme units/A260 unit of chromatin at pH 6.6), 11% of the input chromatin DNA is found in the Mg2+ -soluble fraction. This DNA has a weight-average single-strand length of about 400 nucleotides and, as determined by renaturation kinetics, comprises a subset of nonrepetitive DNA sequences and a subset of families of middle repetitive sequences. This demonstrates the nonrandom distribution of repetitive and single copy sequences in the Mg2+ -soluble fraction of chromatin. Previous studies have shown that the Mg2+ -soluble fraction is enriched in nonrepeated sequences which are transcribed in vivo (Gottesfeld, J.M., Garrard, W.T., Bagi, G., Wilson, R.F., and Bonner, J. (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 2193-2197). We now report that the Mg2+ -soluble fraction of liver chromatin contains a low proportion of sequences in common with the Mg2+ -soluble fraction of brain chromatin. Thus, fractionation does not depend on some general property of chromatin but is specific with regard to the template activity of the tissue from which the chromatin was obtained.", "contents": "Sequence composition of the template-active fraction of rat liver chromatin. Rat liver chromatin has been separated into nuclease-sensitive and -resistant fractions after mild digestion with DNAase II. The nuclease-sensitive material is further fractionated into Mg2+ -soluble and -insoluble chromatin fractions. The kinetics of production of these chromatin fractions have been investigated. After a brief enzyme treatment (5 min at 10 enzyme units/A260 unit of chromatin at pH 6.6), 11% of the input chromatin DNA is found in the Mg2+ -soluble fraction. This DNA has a weight-average single-strand length of about 400 nucleotides and, as determined by renaturation kinetics, comprises a subset of nonrepetitive DNA sequences and a subset of families of middle repetitive sequences. This demonstrates the nonrandom distribution of repetitive and single copy sequences in the Mg2+ -soluble fraction of chromatin. Previous studies have shown that the Mg2+ -soluble fraction is enriched in nonrepeated sequences which are transcribed in vivo (Gottesfeld, J.M., Garrard, W.T., Bagi, G., Wilson, R.F., and Bonner, J. (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 2193-2197). We now report that the Mg2+ -soluble fraction of liver chromatin contains a low proportion of sequences in common with the Mg2+ -soluble fraction of brain chromatin. Thus, fractionation does not depend on some general property of chromatin but is specific with regard to the template activity of the tissue from which the chromatin was obtained."} {"id": "PMID:179569", "title": "Divergent effects of adrenocorticotropin and melanotropin on isolated rat and rabbit adipocytes.", "content": "The stimulation of lipolysis in isolated rat and rabbit fat cells by adrenocorticotropin (ACTH) and alpha-melanotropin has been studied. The concentration of alpha-melanotropin required for half maximal stimulation is 0.23 times that of ACTH in rabbit adipocytes but as high as 1140 times that of ACTH in rat fat cells. Chemical modification of the tryptophan residue in ACTH and melanotropin resulted in a loss of lipolytic activity in rat adipocytes and an increase in lipolytic potency in rabbit fat cells. These differences between rat and rabbit fat cells were evident when stimulation of cyclic AMP synthesis was measured in isolated cells or ghosts. The results are discussed in terms of the difference in the hormone receptors of the fat cells of the two species.", "contents": "Divergent effects of adrenocorticotropin and melanotropin on isolated rat and rabbit adipocytes. The stimulation of lipolysis in isolated rat and rabbit fat cells by adrenocorticotropin (ACTH) and alpha-melanotropin has been studied. The concentration of alpha-melanotropin required for half maximal stimulation is 0.23 times that of ACTH in rabbit adipocytes but as high as 1140 times that of ACTH in rat fat cells. Chemical modification of the tryptophan residue in ACTH and melanotropin resulted in a loss of lipolytic activity in rat adipocytes and an increase in lipolytic potency in rabbit fat cells. These differences between rat and rabbit fat cells were evident when stimulation of cyclic AMP synthesis was measured in isolated cells or ghosts. The results are discussed in terms of the difference in the hormone receptors of the fat cells of the two species."} {"id": "PMID:179570", "title": "Comparison of the steroidogenic and melanotropic activities of corticotropin, alpha-melanotropin and analogs with their lipolytic activities in rat and rabbit adipocytes.", "content": "The ability of alpha-melanotropin and a series of synthetic peptides related to adrenocorticotropin (ACTH) to stimulate steroidogenesis in isolated rat adrenal cells, melanin dispersion in frog melanophores and lipolysis in rat and rabbit fat cells have been studied. It was found that the steroidogenic activity closely paralleled the lipolytic activity of these peptides in rat fat cells, whereas the melanocyte stimulating activity paralleled the lipolytic activity in rabbit fat cells. These results indicate that the structural requirements for stimulating steroidogenesis in isolated rat adrenal cells and lipolysis in isolated rat fat cells are quite similar. The structural features required for eliciting lipolysis in rabbit fat cells appear to be very similar to those necessary for stimulating frog melanophores. The possibility that regulation of lipid metabolism in the rabbit may be a new function acquired by melanotropin is discussed.", "contents": "Comparison of the steroidogenic and melanotropic activities of corticotropin, alpha-melanotropin and analogs with their lipolytic activities in rat and rabbit adipocytes. The ability of alpha-melanotropin and a series of synthetic peptides related to adrenocorticotropin (ACTH) to stimulate steroidogenesis in isolated rat adrenal cells, melanin dispersion in frog melanophores and lipolysis in rat and rabbit fat cells have been studied. It was found that the steroidogenic activity closely paralleled the lipolytic activity of these peptides in rat fat cells, whereas the melanocyte stimulating activity paralleled the lipolytic activity in rabbit fat cells. These results indicate that the structural requirements for stimulating steroidogenesis in isolated rat adrenal cells and lipolysis in isolated rat fat cells are quite similar. The structural features required for eliciting lipolysis in rabbit fat cells appear to be very similar to those necessary for stimulating frog melanophores. The possibility that regulation of lipid metabolism in the rabbit may be a new function acquired by melanotropin is discussed."} {"id": "PMID:179571", "title": "Roles of alpha and beta adrenergic receptors in control of glucose oxidation in hamster epididymal adipocytes.", "content": "Oxidation of [14C] glucose in isolated epididymal adipocytes from Golden hamsters was stimulated by isoproterenol, epinephrine and norepinephrine, which all interact with beta-adrenergic receptors and by adrenocorticotrophic hormone. In contrast alpha-receptor agonists, such as phenylephrine, methoxamine or clonidine did not increase basal glucose oxidation. The beta-adrenergic blocking drug propranolol inhibited both lipolysis and glucose oxidation when these had been stimulated by isoproterenol, epinephrine or norepinephrine. Conversely, the alpha-adrenergic blocking drugs phentolamine and phenoxybenzamine did not influence lipolysis or glucose oxidation when isoproterenol provided the stimulus and increased both lipolysis and glucose metabolism in the present of either epinephrine or norepinephrine. All alpha-adrenergic agonists tested (phenylephrine, methoxamine and clonidine) lowered lipolysis and glucose oxidation isolated adipocytes exposed to isoproterenol. However, when adrenocorticotropin provided the stimulus for glucose oxidation and lipolysis, only clonidine produced a significant reduction in lipolysis and glucose oxidation. None of the alpha-agonists influenced glucose metabolism which had been increased by insulin. These data confirm the presence of both alpha and beta adrenergic receptors on hamster epididymal adipocytes and suggest that they exert antagonistic influences on lipolysis and glucose oxidation. These data are also consistent with the view that adrenergic stimulation of glucose oxidation and lipolysis in adipocytes are both mediated through beta receptors.", "contents": "Roles of alpha and beta adrenergic receptors in control of glucose oxidation in hamster epididymal adipocytes. Oxidation of [14C] glucose in isolated epididymal adipocytes from Golden hamsters was stimulated by isoproterenol, epinephrine and norepinephrine, which all interact with beta-adrenergic receptors and by adrenocorticotrophic hormone. In contrast alpha-receptor agonists, such as phenylephrine, methoxamine or clonidine did not increase basal glucose oxidation. The beta-adrenergic blocking drug propranolol inhibited both lipolysis and glucose oxidation when these had been stimulated by isoproterenol, epinephrine or norepinephrine. Conversely, the alpha-adrenergic blocking drugs phentolamine and phenoxybenzamine did not influence lipolysis or glucose oxidation when isoproterenol provided the stimulus and increased both lipolysis and glucose metabolism in the present of either epinephrine or norepinephrine. All alpha-adrenergic agonists tested (phenylephrine, methoxamine and clonidine) lowered lipolysis and glucose oxidation isolated adipocytes exposed to isoproterenol. However, when adrenocorticotropin provided the stimulus for glucose oxidation and lipolysis, only clonidine produced a significant reduction in lipolysis and glucose oxidation. None of the alpha-agonists influenced glucose metabolism which had been increased by insulin. These data confirm the presence of both alpha and beta adrenergic receptors on hamster epididymal adipocytes and suggest that they exert antagonistic influences on lipolysis and glucose oxidation. These data are also consistent with the view that adrenergic stimulation of glucose oxidation and lipolysis in adipocytes are both mediated through beta receptors."} {"id": "PMID:179572", "title": "Maternal-perinatal interrelationships of vitamin D metabolism in rats.", "content": "In pregnant rats it has been possible to show that the distribution of cholecalciferol metabolites in their fetuses reflects the distribution of these metabolites in the blood. In these experiments, pregnant rats were maintained on a vitamin D deficient diet but were supplemented with radiolabelled cholecalciferol. The metabolites found were 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, to a lesser extent, cholecalciferol. 1,25-Dihydroxycholecalciferol was not detected in fetal tissues, despite the ability of fetal kidney homogenates to hydroxylate 25-hydroxycholecalciferol in C-1. Kidney homogenates of newborn pups were found to possess marked activity of 25-hydroxycholecalciferol-24-hydroxylase, which was retained even in hypocalcemic pups born to pregnant rats that were fed a low-calcium diet. Injection of radiolabeled cholecalciferol to newborn pups resulted in the formation of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol. 1,25-Dihydroxycholecalciferol was not detected. Tissues thought of as target organs for vitamin D (in pregnant rats), namely, intestine, kidney and bone, were found to contain none or very little 1,25-dihydroxycholecalciferol. Mammary glands obtained from lactating rats were found to contain mainly the unchanged vitamin.", "contents": "Maternal-perinatal interrelationships of vitamin D metabolism in rats. In pregnant rats it has been possible to show that the distribution of cholecalciferol metabolites in their fetuses reflects the distribution of these metabolites in the blood. In these experiments, pregnant rats were maintained on a vitamin D deficient diet but were supplemented with radiolabelled cholecalciferol. The metabolites found were 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, to a lesser extent, cholecalciferol. 1,25-Dihydroxycholecalciferol was not detected in fetal tissues, despite the ability of fetal kidney homogenates to hydroxylate 25-hydroxycholecalciferol in C-1. Kidney homogenates of newborn pups were found to possess marked activity of 25-hydroxycholecalciferol-24-hydroxylase, which was retained even in hypocalcemic pups born to pregnant rats that were fed a low-calcium diet. Injection of radiolabeled cholecalciferol to newborn pups resulted in the formation of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol. 1,25-Dihydroxycholecalciferol was not detected. Tissues thought of as target organs for vitamin D (in pregnant rats), namely, intestine, kidney and bone, were found to contain none or very little 1,25-dihydroxycholecalciferol. Mammary glands obtained from lactating rats were found to contain mainly the unchanged vitamin."} {"id": "PMID:179573", "title": "The dependence of specific nuclear binding of glucocorticoids by rat thymus cells on cellular ATP levels.", "content": "The specific, saturable, nuclear binding of corticosteroids by rat thymus cells has been studied. Both the accumulation and the retention of corticosteroids by the nuclei of rat thymus cells at 37 degrees C were dependent upon the metabolic state of the cells. Treatment of cells with 2,4-dinitrophenol in the absence of glucose inhibited both accumulation and retention in the cell nucleus; these effects could be only partially prevented by the addition of glucose. The presence or absence of glucose also influenced the level of nuclear binding in the absence of 2,4-dinitrophenol, and in all cases the levels of nuclear binding of corticosteroids were correlated with cellular ATP levels. The effects of other reagents on levels of ATP and cyclic AMP also showed that significant changes in the level of nuclear-bound steroid were always accompanied by parallel variations in ATP levels, although there were no such correlations with levels of cyclic AMP. The partial restoration of nuclear binding by glucose in cells previously treated with 2,4-dinitrophenol was unaffected by cycloheximiede although protein synthesis was inhibited. Possible mechanisms by which the corticosteroid receptor is converted to a form capable of binding steroids by a reaction which requires energy but not de nova protein synthesis are discussed.", "contents": "The dependence of specific nuclear binding of glucocorticoids by rat thymus cells on cellular ATP levels. The specific, saturable, nuclear binding of corticosteroids by rat thymus cells has been studied. Both the accumulation and the retention of corticosteroids by the nuclei of rat thymus cells at 37 degrees C were dependent upon the metabolic state of the cells. Treatment of cells with 2,4-dinitrophenol in the absence of glucose inhibited both accumulation and retention in the cell nucleus; these effects could be only partially prevented by the addition of glucose. The presence or absence of glucose also influenced the level of nuclear binding in the absence of 2,4-dinitrophenol, and in all cases the levels of nuclear binding of corticosteroids were correlated with cellular ATP levels. The effects of other reagents on levels of ATP and cyclic AMP also showed that significant changes in the level of nuclear-bound steroid were always accompanied by parallel variations in ATP levels, although there were no such correlations with levels of cyclic AMP. The partial restoration of nuclear binding by glucose in cells previously treated with 2,4-dinitrophenol was unaffected by cycloheximiede although protein synthesis was inhibited. Possible mechanisms by which the corticosteroid receptor is converted to a form capable of binding steroids by a reaction which requires energy but not de nova protein synthesis are discussed."} {"id": "PMID:179574", "title": "Optimum conditions for the binding of insulin to its receptor.", "content": "The specific binding of insulin to the membranes from lactating mouse mammary gland was studied as a model of hormonereceptor type of binding. The basic ingredients of binding, the concentration of receptor protein and the concentration of labeled insulin were mainly studied. The characteristic changes in specific binding were followed, the adequate regression equation was draen and the optimum conditions of binding were established for further experiments. The expediency of applying shortened orthogonal plans, regression and analysis and graphic conture analysis were proved.", "contents": "Optimum conditions for the binding of insulin to its receptor. The specific binding of insulin to the membranes from lactating mouse mammary gland was studied as a model of hormonereceptor type of binding. The basic ingredients of binding, the concentration of receptor protein and the concentration of labeled insulin were mainly studied. The characteristic changes in specific binding were followed, the adequate regression equation was draen and the optimum conditions of binding were established for further experiments. The expediency of applying shortened orthogonal plans, regression and analysis and graphic conture analysis were proved."} {"id": "PMID:179575", "title": "The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures.", "content": "Quiescent, contact inhibited H-35 rat hepatoma cell cultures maintained in minimal essential medium contain a very low level of ornithine decarboxylase activity. However, 2 h after the addition of 10% fetal calf serum to the culture medium, the enzyme activity increases by approx. 100-fold. This increase can be completely inhibited by the simultaneous addition of 10(-2) M putrescine. The presence of putrescine elicits the appearance of an intracellular inhibitor of ornithine decarboxylase. This inhibitor of ornithine decarboxylase has a molecular weight of 26500, is sensitive to the action of chymotrypsin and is noncompetitive with respect to ornithine. The intracellular appearance of this inhibitor is sensitive to cycloheximide but is only partially inhibited by actinomycin D.", "contents": "The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures. Quiescent, contact inhibited H-35 rat hepatoma cell cultures maintained in minimal essential medium contain a very low level of ornithine decarboxylase activity. However, 2 h after the addition of 10% fetal calf serum to the culture medium, the enzyme activity increases by approx. 100-fold. This increase can be completely inhibited by the simultaneous addition of 10(-2) M putrescine. The presence of putrescine elicits the appearance of an intracellular inhibitor of ornithine decarboxylase. This inhibitor of ornithine decarboxylase has a molecular weight of 26500, is sensitive to the action of chymotrypsin and is noncompetitive with respect to ornithine. The intracellular appearance of this inhibitor is sensitive to cycloheximide but is only partially inhibited by actinomycin D."} {"id": "PMID:179576", "title": "The absence of 2,3-diphosphoglycerate from myocytes, hepatocytes and adipocytes.", "content": "Myocytes, hepatocytes and adipocytes were prepared from heart, liver and epididymal fat pad of the rat. No detectable level of 2,3-diphosphoglycerate was found. Evidence is also presented which indicates the absence from these cells of 2,3-diphosphoglycerate mutase and 2,3-diphosphoglycerate phosphatase. Previous findings by others of the presence of 2,3-diphosphoglycerate and 2,3-diphosphoglycerate mutase probably resulted from erythrocytes sequestered in the tissue.", "contents": "The absence of 2,3-diphosphoglycerate from myocytes, hepatocytes and adipocytes. Myocytes, hepatocytes and adipocytes were prepared from heart, liver and epididymal fat pad of the rat. No detectable level of 2,3-diphosphoglycerate was found. Evidence is also presented which indicates the absence from these cells of 2,3-diphosphoglycerate mutase and 2,3-diphosphoglycerate phosphatase. Previous findings by others of the presence of 2,3-diphosphoglycerate and 2,3-diphosphoglycerate mutase probably resulted from erythrocytes sequestered in the tissue."} {"id": "PMID:179577", "title": "Secretory processes, carbohydrate and lipid metabolism in isolated mouse hepatocytes. Aspects of regulation by glucagon and insulin.", "content": "The procedure of Berry and Friend for isolation of intact hepatocytes has been adapted to mouse livers. The ultrastructure of these cells was satisfactorily preserved. Isolated mouse hepatocytes secreted proteins and triacylglycerols. These secretory processes were inhibited by colchicine, indicating a likely involvement of the microtubular system for their normal occurrence. Ultracentrifugation of medium incubated with hepatocytes, followed by electrophoresis and electron microscopic examination of the floating fraction (density less than 1.006) allowed to conclude that secreted triacylglycerols were very low density lipoproteins. Glycogenolysis and lipogenesis were stimulated or inhibited, respectively, by low concentrations of glucagon (10(-10) M). Other metabolic parameters were influenced by the hormone but were less sensitive to its action. Inhibition of lipogenesis by glucagon was associated with a decrease in acetyl CoA carboxylase activity. This decrease does not appear to be related to intracellular fatty acyl-CoA accumulation secondary to hepatic lipase activation by the hormone. Insulin was effective alone or counteracted glucagon effects on lipogenesis or glycogenolysis only when exposure of cells to collagenase was held minimal. This suggests that, during isolation of hepatocytes, insulin receptors may, for unknown reasons, be more fragile than those of glucagon.", "contents": "Secretory processes, carbohydrate and lipid metabolism in isolated mouse hepatocytes. Aspects of regulation by glucagon and insulin. The procedure of Berry and Friend for isolation of intact hepatocytes has been adapted to mouse livers. The ultrastructure of these cells was satisfactorily preserved. Isolated mouse hepatocytes secreted proteins and triacylglycerols. These secretory processes were inhibited by colchicine, indicating a likely involvement of the microtubular system for their normal occurrence. Ultracentrifugation of medium incubated with hepatocytes, followed by electrophoresis and electron microscopic examination of the floating fraction (density less than 1.006) allowed to conclude that secreted triacylglycerols were very low density lipoproteins. Glycogenolysis and lipogenesis were stimulated or inhibited, respectively, by low concentrations of glucagon (10(-10) M). Other metabolic parameters were influenced by the hormone but were less sensitive to its action. Inhibition of lipogenesis by glucagon was associated with a decrease in acetyl CoA carboxylase activity. This decrease does not appear to be related to intracellular fatty acyl-CoA accumulation secondary to hepatic lipase activation by the hormone. Insulin was effective alone or counteracted glucagon effects on lipogenesis or glycogenolysis only when exposure of cells to collagenase was held minimal. This suggests that, during isolation of hepatocytes, insulin receptors may, for unknown reasons, be more fragile than those of glucagon."} {"id": "PMID:179578", "title": "Activation of protein kinase(s) by glucagon and cyclic AMP in the rat liver. Relationship to metabolic effects.", "content": "Although it is known that protein kinases are activated by cyclic AMP, the role of the activated kinase in the gluconeogenic response to cyclic AMP is not known. Therefore, we examined whether the inhibition of the gluconeogenic response in the liver is due to an interference with the activation of protein kinase in the following situations: (1) adrenalectomy, (2) Na+-free perfusate, (3) administration of local anesthetic. We measured protein kinase activity indirectly by measuring incorporation of 32P into proteins of the perfused liver, and directly by measuring the enzyme activity. We found no significant inhibition of activation of protein kinase in the above experimental conditions. It seems that in the intact liver, activation of protein kinase by itself is not sufficient to evoke metabolic responses. In order to clarify whether the requirement for ion redistribution is specific for the gluconeogenic response or not, the lipolytic and antilipogenic effects of glucagon and cyclic AMP were examined. Na+-free perfusate, local anesthetic or high K+ did interfere with the lipolytic and antilipogenic responses to these agents just as it interfered with the gluconeogenic response. It is likely that ion redistribution evoked by glucagon and cyclic AMP is essential to the expression of most, if not all, metabolic effects.", "contents": "Activation of protein kinase(s) by glucagon and cyclic AMP in the rat liver. Relationship to metabolic effects. Although it is known that protein kinases are activated by cyclic AMP, the role of the activated kinase in the gluconeogenic response to cyclic AMP is not known. Therefore, we examined whether the inhibition of the gluconeogenic response in the liver is due to an interference with the activation of protein kinase in the following situations: (1) adrenalectomy, (2) Na+-free perfusate, (3) administration of local anesthetic. We measured protein kinase activity indirectly by measuring incorporation of 32P into proteins of the perfused liver, and directly by measuring the enzyme activity. We found no significant inhibition of activation of protein kinase in the above experimental conditions. It seems that in the intact liver, activation of protein kinase by itself is not sufficient to evoke metabolic responses. In order to clarify whether the requirement for ion redistribution is specific for the gluconeogenic response or not, the lipolytic and antilipogenic effects of glucagon and cyclic AMP were examined. Na+-free perfusate, local anesthetic or high K+ did interfere with the lipolytic and antilipogenic responses to these agents just as it interfered with the gluconeogenic response. It is likely that ion redistribution evoked by glucagon and cyclic AMP is essential to the expression of most, if not all, metabolic effects."} {"id": "PMID:179579", "title": "Demonstration of adenylate cyclase activity in human red blood cell ghosts.", "content": "The presence of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) activity was demonstrated in human erythrocyte ghosts and was found to be around 3 pmol adenosine 3',5'-monophosphate (cyclic AMP) - 2 h-1 - mg-1 protein. This enzymatic activity is strongly stimulated by NaF and 5'-guanylimidodiphosphate, is slightly stimulated by epinephrine, norepinephrine, isoproterenol, and prostaglandin E1 and is inhibited by calcium. The hormone stimulation is not potentiated by 5'-guanylylimidodiphosphate.", "contents": "Demonstration of adenylate cyclase activity in human red blood cell ghosts. The presence of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) activity was demonstrated in human erythrocyte ghosts and was found to be around 3 pmol adenosine 3',5'-monophosphate (cyclic AMP) - 2 h-1 - mg-1 protein. This enzymatic activity is strongly stimulated by NaF and 5'-guanylimidodiphosphate, is slightly stimulated by epinephrine, norepinephrine, isoproterenol, and prostaglandin E1 and is inhibited by calcium. The hormone stimulation is not potentiated by 5'-guanylylimidodiphosphate."} {"id": "PMID:179580", "title": "Premature induction of amylase in pancreas and parotid gland of growing rats by dexamethasone.", "content": "Studies were made on changes in the contents of alpha-amylase (EC 3.2.1.1) in the pancreas and parotid gland of rats during postnatal development, on the premature induction of this enzyme by hormones and on the existence of specific glucocorticoid receptors in these tissues. The amylase content in the pancreas increased from the 9th day after birth and reached the adult level on the 28th day, its content in the parotid gland increased rapidly from the 16th to the 28th day after birth and then rose more gradually to the adult level. Injection of dexamethasone into rats 6--8 days after birth induced increase in the amylase of the pancreas but not the parotid gland. However, injection of dexamethasone into weanling rats 21--23 days after birth resulted in precocious induction of amylase in both tissues. Specific glucocorticoid receptors were detectable in the parotid gland of rats from 6 days after birth but were almost undetectable in the pancreas until adolescence.", "contents": "Premature induction of amylase in pancreas and parotid gland of growing rats by dexamethasone. Studies were made on changes in the contents of alpha-amylase (EC 3.2.1.1) in the pancreas and parotid gland of rats during postnatal development, on the premature induction of this enzyme by hormones and on the existence of specific glucocorticoid receptors in these tissues. The amylase content in the pancreas increased from the 9th day after birth and reached the adult level on the 28th day, its content in the parotid gland increased rapidly from the 16th to the 28th day after birth and then rose more gradually to the adult level. Injection of dexamethasone into rats 6--8 days after birth induced increase in the amylase of the pancreas but not the parotid gland. However, injection of dexamethasone into weanling rats 21--23 days after birth resulted in precocious induction of amylase in both tissues. Specific glucocorticoid receptors were detectable in the parotid gland of rats from 6 days after birth but were almost undetectable in the pancreas until adolescence."} {"id": "PMID:179581", "title": "Acute effects of oral and intravenous ethanol on rat hepatic enzyme activities.", "content": "1. Oral administration of ethanol (3 ml) of 95% in 12 ml total volume over a two day period) significantly decrease plasma glucose and insulin levels and the activities of two key gluconeogenic enzymes, pyruvate carboxylase (pyruvate: CO2 ligase (ADP), EC 6.4.1.1) and fructose diphosphatase, (D-Fru-1,6-P2 1-phosphohydrolase, EC 3.1.3.11), and one glycolytic enzyme, fructose-1,6-P2 aldolase (Fru-1,6-P2 D-glyceraldehyde-3-P lyase, EC 4.1.2.13). In each instance, the administration of 2400 mug daily of oral folate in conjuction with the ethanol prevented these alterations in carbohydrate metabolism. 2. Intravenous injection of ethanol produced a rapid decrease (within 10--15 min) in the activities of hepatic phosphofructokinase, (ATP:D-fructose-6-phosphate 6-phosphotransferase, EC 2.7.1.11), pyruvate kinase, (ATP:pyruvate phosphotransferase, EC 2.7.1.40), fructose diphosphatase and fructose-1,6-P2 aldolase. 3. Intravenous ethanol significantly increased hepatic cyclic AMP concentration approximately 60% within 10 min, while oral ethanol did not alter hepatic cyclic AMP concentrations. 4. These data confirm the known antagonism ethanol and folate and suggest that oral folate might offer a protective effect against hypoglycemia in rats receiving ethanol.", "contents": "Acute effects of oral and intravenous ethanol on rat hepatic enzyme activities. 1. Oral administration of ethanol (3 ml) of 95% in 12 ml total volume over a two day period) significantly decrease plasma glucose and insulin levels and the activities of two key gluconeogenic enzymes, pyruvate carboxylase (pyruvate: CO2 ligase (ADP), EC 6.4.1.1) and fructose diphosphatase, (D-Fru-1,6-P2 1-phosphohydrolase, EC 3.1.3.11), and one glycolytic enzyme, fructose-1,6-P2 aldolase (Fru-1,6-P2 D-glyceraldehyde-3-P lyase, EC 4.1.2.13). In each instance, the administration of 2400 mug daily of oral folate in conjuction with the ethanol prevented these alterations in carbohydrate metabolism. 2. Intravenous injection of ethanol produced a rapid decrease (within 10--15 min) in the activities of hepatic phosphofructokinase, (ATP:D-fructose-6-phosphate 6-phosphotransferase, EC 2.7.1.11), pyruvate kinase, (ATP:pyruvate phosphotransferase, EC 2.7.1.40), fructose diphosphatase and fructose-1,6-P2 aldolase. 3. Intravenous ethanol significantly increased hepatic cyclic AMP concentration approximately 60% within 10 min, while oral ethanol did not alter hepatic cyclic AMP concentrations. 4. These data confirm the known antagonism ethanol and folate and suggest that oral folate might offer a protective effect against hypoglycemia in rats receiving ethanol."} {"id": "PMID:179582", "title": "Inhibition of growth and aspartokinase activity of Salmonella typhimurium by thialysine.", "content": "Thialysine (S-2-aminoethyl cysteine) is an analog of lysine and has been reported to inhibit the lysyl-tRNA synthetase activity of Escherichia coli. This analog inhibits the growth of Salmonella typhimurium when added to glucose minimal medium at concentrations of 1.25 mM or greater. The addition of lysine with thialysine restores the normal growth rate, whereas, methionine, valine, or leucine each enhances the growth inhibition casued by thialysine. Enzyme assays demonstrate that thialysine inhibits not only the lysyl-tRNA synthetase from S. typhimurium, but also the aspartokinase activity. Lysine and thialysine appear to inhibit the same 40% of the total aspartokinase because simultaneous addition of the two compounds to the reaction mixture does not increase the inhibition caused by either alone. Furthermore, the slow growth of cells in the presence of 2.5 mM thialysine decreases the level of aspartokinase activity, suggesting that thialysine causes repression of enzyme synthesis as well as inhibition of activity.", "contents": "Inhibition of growth and aspartokinase activity of Salmonella typhimurium by thialysine. Thialysine (S-2-aminoethyl cysteine) is an analog of lysine and has been reported to inhibit the lysyl-tRNA synthetase activity of Escherichia coli. This analog inhibits the growth of Salmonella typhimurium when added to glucose minimal medium at concentrations of 1.25 mM or greater. The addition of lysine with thialysine restores the normal growth rate, whereas, methionine, valine, or leucine each enhances the growth inhibition casued by thialysine. Enzyme assays demonstrate that thialysine inhibits not only the lysyl-tRNA synthetase from S. typhimurium, but also the aspartokinase activity. Lysine and thialysine appear to inhibit the same 40% of the total aspartokinase because simultaneous addition of the two compounds to the reaction mixture does not increase the inhibition caused by either alone. Furthermore, the slow growth of cells in the presence of 2.5 mM thialysine decreases the level of aspartokinase activity, suggesting that thialysine causes repression of enzyme synthesis as well as inhibition of activity."} {"id": "PMID:179583", "title": "Growth of a mutant of Escherichia coli K-12 on xylitol by recruiting enzymes for D-xylose and L1,2-propanediol metabolism.", "content": "Wild type Escherichia coli K-12 cannot grow on xylitol and we have been unsuccessful in isolating a mutant directly which had acquired this new growth ability. However, a mutant had been selected previously for growth on L-1,2-propanediol as the sole source of carbon and energy. This mutant constitutively synthesized a propanediol dehydrogenase. Recently, we have found that this dehydrogenase fortuitously converted xylitol to D-xylose which could normally be metabolized by E. coli K-12. In addition, it was also discovered that the D-xylose permease fortuitously transported xylitol into the cell. A second mutant was thus isolated from the L-1,2-propanediol-growing mutant that was constitutive for the enzymes of the D-xylose pathway. This mutant could indeed grow on xylitol as the sole source of carbon and energy, by utilizing the enzymes normally involved in D-xylose and L-1,2-propanediol metabolism.", "contents": "Growth of a mutant of Escherichia coli K-12 on xylitol by recruiting enzymes for D-xylose and L1,2-propanediol metabolism. Wild type Escherichia coli K-12 cannot grow on xylitol and we have been unsuccessful in isolating a mutant directly which had acquired this new growth ability. However, a mutant had been selected previously for growth on L-1,2-propanediol as the sole source of carbon and energy. This mutant constitutively synthesized a propanediol dehydrogenase. Recently, we have found that this dehydrogenase fortuitously converted xylitol to D-xylose which could normally be metabolized by E. coli K-12. In addition, it was also discovered that the D-xylose permease fortuitously transported xylitol into the cell. A second mutant was thus isolated from the L-1,2-propanediol-growing mutant that was constitutive for the enzymes of the D-xylose pathway. This mutant could indeed grow on xylitol as the sole source of carbon and energy, by utilizing the enzymes normally involved in D-xylose and L-1,2-propanediol metabolism."} {"id": "PMID:179585", "title": "Transformation of glucocorticoid-receptor complex from rat thymocytes and its accumulation in chromatin in a cell-free system.", "content": "The accumulation of glucocorticoid-receptor complex from rat thymocyte cytosol in a thymocyte chromatin preparation has been studied. A thymocyte 100 000 X g supernatant was prepared and the receptor and the receptor stabilized by the addition of glycerol until 40%. Tritiated glucocorticoid-receptor complex was formed by incubation of this solution with tritiated glucocorticoids at -5 degree C. The chromatin accumulated part of the complex at incubations at 4 degrees C. Receptor without hormone was not accumulated in the chromatin. The accumulation from cytosol diluted and preincubated at 4 degrees C prior to the addition of the chromatin occurred with a high rate, whereas a low rate was seen without preincubation. This indicated a transformation of the complex during the preincubation. This transformation was found to be obligatory for the accumulation and to be promoted by dilution of the supernatant and by high ionic strength. The transformed and the untransformed complexes differed with respect to partition coefficients in an aqueous dextran-polyethylene glycol two-phase system and in their behaviour during adsorptions with dextran-coated charcoal, where great loss of transformed complex was observed. The accumulation of complex in the chromatin was found to be unsaturable in the concentration interval studied (0.07--0.25 nM).", "contents": "Transformation of glucocorticoid-receptor complex from rat thymocytes and its accumulation in chromatin in a cell-free system. The accumulation of glucocorticoid-receptor complex from rat thymocyte cytosol in a thymocyte chromatin preparation has been studied. A thymocyte 100 000 X g supernatant was prepared and the receptor and the receptor stabilized by the addition of glycerol until 40%. Tritiated glucocorticoid-receptor complex was formed by incubation of this solution with tritiated glucocorticoids at -5 degree C. The chromatin accumulated part of the complex at incubations at 4 degrees C. Receptor without hormone was not accumulated in the chromatin. The accumulation from cytosol diluted and preincubated at 4 degrees C prior to the addition of the chromatin occurred with a high rate, whereas a low rate was seen without preincubation. This indicated a transformation of the complex during the preincubation. This transformation was found to be obligatory for the accumulation and to be promoted by dilution of the supernatant and by high ionic strength. The transformed and the untransformed complexes differed with respect to partition coefficients in an aqueous dextran-polyethylene glycol two-phase system and in their behaviour during adsorptions with dextran-coated charcoal, where great loss of transformed complex was observed. The accumulation of complex in the chromatin was found to be unsaturable in the concentration interval studied (0.07--0.25 nM)."} {"id": "PMID:179586", "title": "Phospholipases and the effect of prolactin on uridine incorporation into RNA in mammary gland explants of mice.", "content": "The possible effects of phospholipase A and phospholipase C on the rate of uridine incorporation into RNA in mammary gland explants of mice were tested. Phospholipase C had no effect on the rate of uridine incorporation, but it did suppress the action of prolactin on this metabolic parameter. In contrast, phospholipase A was found to stimulate the rate of uridine incorporation into RNA in a manner similar to that of prolactin. The time-courses for the onset of the prolactin and phospholipase A effects were the same. Also, the phospholipase A effect was nonadditive to the effect produced by a maximally stimulatory concentration of prolactin. Finally it was observed that, like the prolactin effect, the phospholipase A effect was abolished by incubation with dibutyryl cyclic AMP, theophylline, quinine, indomethacin and prostaglandin E1. Further, the phospholipase A effect was nonadditive to the prolactin-like effects produced by the cyclic GMP, prostaglandin F2alpha or arachidonic acid. These data therefore suggest that prolactin and phospholipase A stimulate RNA synthesis in mammary gland explants via similar processes.", "contents": "Phospholipases and the effect of prolactin on uridine incorporation into RNA in mammary gland explants of mice. The possible effects of phospholipase A and phospholipase C on the rate of uridine incorporation into RNA in mammary gland explants of mice were tested. Phospholipase C had no effect on the rate of uridine incorporation, but it did suppress the action of prolactin on this metabolic parameter. In contrast, phospholipase A was found to stimulate the rate of uridine incorporation into RNA in a manner similar to that of prolactin. The time-courses for the onset of the prolactin and phospholipase A effects were the same. Also, the phospholipase A effect was nonadditive to the effect produced by a maximally stimulatory concentration of prolactin. Finally it was observed that, like the prolactin effect, the phospholipase A effect was abolished by incubation with dibutyryl cyclic AMP, theophylline, quinine, indomethacin and prostaglandin E1. Further, the phospholipase A effect was nonadditive to the prolactin-like effects produced by the cyclic GMP, prostaglandin F2alpha or arachidonic acid. These data therefore suggest that prolactin and phospholipase A stimulate RNA synthesis in mammary gland explants via similar processes."} {"id": "PMID:179587", "title": "The one-electron transfer redox potentials of free radicals. I. The oxygen/superoxide system.", "content": "The method of determination of Redox potentials of radicals, using the pulse radiolysis technique, is outlined. The method is based on the determination of equilibrium constants of electron transfer reactions between the radicals and appropriate acceptors. The limitations of this technique are discussed. The redox potentials of several quinones-semiquinones are calculated, as well as the standard redox potential of the peroxy radical. EO2/O2=-0.33 V and the redox oxidation properties of the peroxy radical in various systems and pH are discussed. The value determined for the redox potentials of O2/O2 is higher by more than 0.2 V than earlier estimates, which has important implications on the possible role of O2 in biological processes of O2 fixation.", "contents": "The one-electron transfer redox potentials of free radicals. I. The oxygen/superoxide system. The method of determination of Redox potentials of radicals, using the pulse radiolysis technique, is outlined. The method is based on the determination of equilibrium constants of electron transfer reactions between the radicals and appropriate acceptors. The limitations of this technique are discussed. The redox potentials of several quinones-semiquinones are calculated, as well as the standard redox potential of the peroxy radical. EO2/O2=-0.33 V and the redox oxidation properties of the peroxy radical in various systems and pH are discussed. The value determined for the redox potentials of O2/O2 is higher by more than 0.2 V than earlier estimates, which has important implications on the possible role of O2 in biological processes of O2 fixation."} {"id": "PMID:179588", "title": "Compositional characteristics of a chloroform/methanol soluble protein fraction from spinach chloroplast membranes.", "content": "Extraction of an aqueous suspension of spinach chloroplast lamellae with a chloroform/methanol mixture leads to solubilization of about 1/3 of the total membrane protein. Amino acid analysis of the chloroform/methanol-soluble protein shows that this fraction is largely enriched in the hydrophobic residues proline, leucine, alanine and phenylalanine and considerably depleted in polar amino acids, namely lysine and arginine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized material reveals the presence of a variety of low molecular weight polypeptides (molecular weight less than or equal to 25 000), with more than 50% of the total fraction being contributed by a 25 000 dalton band. This band, which accounts for about 25% of the total chloroplast lamellar protein, has recently been identified as the main component of the light-harvesting chlorophyll-protein complex. The physiological role of most of the chloroform/methanol-soluble protein fraction is not known at present. From its chemical properties and apparent biological inertness, we propose that it plays mainly a structural role in situ, interacting with the lipid moiety of the chloroplast membrane. The material insoluble in the aqueous chloroform/methanol mixture is largely enriched in manganese, iron, cytochrome and water-soluble proteins, such as chloroplast coupling factor and ribulose diphosphate carboxylase.", "contents": "Compositional characteristics of a chloroform/methanol soluble protein fraction from spinach chloroplast membranes. Extraction of an aqueous suspension of spinach chloroplast lamellae with a chloroform/methanol mixture leads to solubilization of about 1/3 of the total membrane protein. Amino acid analysis of the chloroform/methanol-soluble protein shows that this fraction is largely enriched in the hydrophobic residues proline, leucine, alanine and phenylalanine and considerably depleted in polar amino acids, namely lysine and arginine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized material reveals the presence of a variety of low molecular weight polypeptides (molecular weight less than or equal to 25 000), with more than 50% of the total fraction being contributed by a 25 000 dalton band. This band, which accounts for about 25% of the total chloroplast lamellar protein, has recently been identified as the main component of the light-harvesting chlorophyll-protein complex. The physiological role of most of the chloroform/methanol-soluble protein fraction is not known at present. From its chemical properties and apparent biological inertness, we propose that it plays mainly a structural role in situ, interacting with the lipid moiety of the chloroplast membrane. The material insoluble in the aqueous chloroform/methanol mixture is largely enriched in manganese, iron, cytochrome and water-soluble proteins, such as chloroplast coupling factor and ribulose diphosphate carboxylase."} {"id": "PMID:179589", "title": "PRoperties of the low-temperature photosystem I primary reaction in the P-700-chlorophyll alpha-protein.", "content": "The Photosystem I primary reaction, as measured by electron paramagnetic resonance changes of P-700 and a bound iron-sulfur center, has been studied at 15 degrees K in P-700-chlorophyll alpha-protein complexes isolated from a blue-green alga. One complex, prepared with sodium dodecyl sulfate shows P-700 photooxidation only at 300 degrees K, whereas a second complex, prepared with Triton X-100, is photochemically active at 15 degrees K as well as at 300 degrees K. Analysis of these two preparations shows that the absence of low-temperature photoactivity in the sodium dodecyl sulfate complex reflects a lack of bound iron-sulfur centers in this preparation and supports the assignment of an iron-sulfur center as the primary electron acceptor of Photosystem I.", "contents": "PRoperties of the low-temperature photosystem I primary reaction in the P-700-chlorophyll alpha-protein. The Photosystem I primary reaction, as measured by electron paramagnetic resonance changes of P-700 and a bound iron-sulfur center, has been studied at 15 degrees K in P-700-chlorophyll alpha-protein complexes isolated from a blue-green alga. One complex, prepared with sodium dodecyl sulfate shows P-700 photooxidation only at 300 degrees K, whereas a second complex, prepared with Triton X-100, is photochemically active at 15 degrees K as well as at 300 degrees K. Analysis of these two preparations shows that the absence of low-temperature photoactivity in the sodium dodecyl sulfate complex reflects a lack of bound iron-sulfur centers in this preparation and supports the assignment of an iron-sulfur center as the primary electron acceptor of Photosystem I."} {"id": "PMID:179590", "title": "The mobile receptor hypothesis and \"cooperativity\" of hormone binding. Application to insulin.", "content": "The mobile receptor hypothesis has been proposed to describe the process by which hormone receptor binding initiates a biological response; it states that receptors, which can diffuse independently in the plane of the membrane, reversibly associate with effectors to regulate their activity. The affinity for effector is greater when the receptor is occupied by hormone. A mathematical expression of the mobile receptor hypothesis is used to show that: (1) The predicted kinetics of hormone receptor binding may be indistinguishable from \"negative cooperativity.\" (2) Receptor occupancy and biological response may be coupled in a non-linear fashion. By choosing specific parameters, most of the existing data on insulin binding and biological responses can be explained in terms of the mobile receptor hypothesis. Thus, the following are easily explained: (1) A single homogeneous receptor may appear kinetically to be composed of two classes (of high and low affinity) of receptors. (2) Occupancy of the apparent class of high affinity receptors is related linearly to the biological response. (3) The same receptor in different tissues may appear to have different affinity. (4) The binding of different biologically active insulin analogues may exhibit different degrees of \"cooperativity.\" These considerations may also be pertinent to interpretations of other hormone-receptor systems and of various ligand-macromolecule interactions.", "contents": "The mobile receptor hypothesis and \"cooperativity\" of hormone binding. Application to insulin. The mobile receptor hypothesis has been proposed to describe the process by which hormone receptor binding initiates a biological response; it states that receptors, which can diffuse independently in the plane of the membrane, reversibly associate with effectors to regulate their activity. The affinity for effector is greater when the receptor is occupied by hormone. A mathematical expression of the mobile receptor hypothesis is used to show that: (1) The predicted kinetics of hormone receptor binding may be indistinguishable from \"negative cooperativity.\" (2) Receptor occupancy and biological response may be coupled in a non-linear fashion. By choosing specific parameters, most of the existing data on insulin binding and biological responses can be explained in terms of the mobile receptor hypothesis. Thus, the following are easily explained: (1) A single homogeneous receptor may appear kinetically to be composed of two classes (of high and low affinity) of receptors. (2) Occupancy of the apparent class of high affinity receptors is related linearly to the biological response. (3) The same receptor in different tissues may appear to have different affinity. (4) The binding of different biologically active insulin analogues may exhibit different degrees of \"cooperativity.\" These considerations may also be pertinent to interpretations of other hormone-receptor systems and of various ligand-macromolecule interactions."} {"id": "PMID:179591", "title": "The surface membrane of the small intestinal epithelial cell. I. Localization of adenyl cyclase.", "content": "The subcellular distribution of adenyl cyclase was investigated in small intestinal epithelial cells. Enterocytes were isolated, disrupted and the resulting membranes fractionated by differential and sucrose gradient centrifugation. Separation of luminal (brush border) and contra-luminal (basolateral) plasma membrane was achieved on a discontinuous sucrose gradient. The activity of adenyl cyclase was followed during fractionation in relation to other enzymes, notably those considered as markers for luminal and contraluminal plasma membrane. The luminal membrane was identified by the membrane-bound enzymes sucrase and alkaline phosphatase and the basolateral region by (Na+ + K+)-ATPase. Enrichment of the former two enzymes in purified luminal plasma membrane was 8-fold over cells and that of (Na+ + K+)-ATPase in purified bisolateral plasma membranes was 13-fold. F--activated adenyl cyclase co-purified with (Na+ + K+)-ATPase, suggesting a common localization on the plasma membrane. The distribution of K+-stimulated phosphatase and 5'-nucleotidase also followed (Na+ + K+)-ATPase during fractionation.", "contents": "The surface membrane of the small intestinal epithelial cell. I. Localization of adenyl cyclase. The subcellular distribution of adenyl cyclase was investigated in small intestinal epithelial cells. Enterocytes were isolated, disrupted and the resulting membranes fractionated by differential and sucrose gradient centrifugation. Separation of luminal (brush border) and contra-luminal (basolateral) plasma membrane was achieved on a discontinuous sucrose gradient. The activity of adenyl cyclase was followed during fractionation in relation to other enzymes, notably those considered as markers for luminal and contraluminal plasma membrane. The luminal membrane was identified by the membrane-bound enzymes sucrase and alkaline phosphatase and the basolateral region by (Na+ + K+)-ATPase. Enrichment of the former two enzymes in purified luminal plasma membrane was 8-fold over cells and that of (Na+ + K+)-ATPase in purified bisolateral plasma membranes was 13-fold. F--activated adenyl cyclase co-purified with (Na+ + K+)-ATPase, suggesting a common localization on the plasma membrane. The distribution of K+-stimulated phosphatase and 5'-nucleotidase also followed (Na+ + K+)-ATPase during fractionation."} {"id": "PMID:179592", "title": "The effect of short chain fatty acids on transmural electrical potential across rat small intestine in vivo.", "content": "Short chain fatty acids suddenly produce a phasic increase in transmural electrical potential difference (PD) when placed in the lumen of rat small intestine in vivo. With concentrations of propionate ranging from 50 muM to 1000 muM the amplitude of the response in jejunum is about 5.5 mV. The concentration giving half this effect is about 20 muM. With 10 mM propionate the duration of the response is 3-5 min; after this, PD again equals the control value and the gut is refractory to further additions. Removing propionate from the mucosal surface produces no change in PD, but does restore responsiveness to subsequent exposure to short chain fatty acids. This effect is independent of a variety of other alterations in PD such as those caused by sugars, amino acids, bile salts, theophylline, prostaglandins, and ATP. Mechanism and significance of this surprisingly sensitive response remain obscure.", "contents": "The effect of short chain fatty acids on transmural electrical potential across rat small intestine in vivo. Short chain fatty acids suddenly produce a phasic increase in transmural electrical potential difference (PD) when placed in the lumen of rat small intestine in vivo. With concentrations of propionate ranging from 50 muM to 1000 muM the amplitude of the response in jejunum is about 5.5 mV. The concentration giving half this effect is about 20 muM. With 10 mM propionate the duration of the response is 3-5 min; after this, PD again equals the control value and the gut is refractory to further additions. Removing propionate from the mucosal surface produces no change in PD, but does restore responsiveness to subsequent exposure to short chain fatty acids. This effect is independent of a variety of other alterations in PD such as those caused by sugars, amino acids, bile salts, theophylline, prostaglandins, and ATP. Mechanism and significance of this surprisingly sensitive response remain obscure."} {"id": "PMID:179593", "title": "Lipid-protein interactions in model membranes from bovine brain white matter. An ESR spin label and electron microscopy study.", "content": "Lipid-protein model membranes, prepared from bovine brain white matter and containing all the lipids and Folch-Lees proteolipids, have been studied in macroscopically oriented multibilayers. To examine the lipid environment the membranes were spin labeled with the cholestane spin label (3'-spiro(2'=(N-oxyl-4',4'-dimethyl-oxazolidine))5alpha-cholestane) and a fatty acid spin label (4',4'-dimethyloxazolidine-N-oxyl derivative of 5-ketostearic acid). The ESR spectra exhibit two components arising from fairly well oriented and completely unoriented lipids. Up to a temperature of 55 degrees C the amount of oriented lipids is almost constant, being about 35%. At higher temperatures this percentage drops rapidly to zero. It is shown that the presence of unoriented lipids arises mainly from disrupted areas in the lipid bilayer structure. This is confirmed by electron miccroscopy and from an analysis of the temperature dependence of the order parameters of the spin labels. The presence of locally disrupted lipid parts in the bilayer is discussed in relation to the interaction of the brain white matter lipids with Folch-Lees protein.", "contents": "Lipid-protein interactions in model membranes from bovine brain white matter. An ESR spin label and electron microscopy study. Lipid-protein model membranes, prepared from bovine brain white matter and containing all the lipids and Folch-Lees proteolipids, have been studied in macroscopically oriented multibilayers. To examine the lipid environment the membranes were spin labeled with the cholestane spin label (3'-spiro(2'=(N-oxyl-4',4'-dimethyl-oxazolidine))5alpha-cholestane) and a fatty acid spin label (4',4'-dimethyloxazolidine-N-oxyl derivative of 5-ketostearic acid). The ESR spectra exhibit two components arising from fairly well oriented and completely unoriented lipids. Up to a temperature of 55 degrees C the amount of oriented lipids is almost constant, being about 35%. At higher temperatures this percentage drops rapidly to zero. It is shown that the presence of unoriented lipids arises mainly from disrupted areas in the lipid bilayer structure. This is confirmed by electron miccroscopy and from an analysis of the temperature dependence of the order parameters of the spin labels. The presence of locally disrupted lipid parts in the bilayer is discussed in relation to the interaction of the brain white matter lipids with Folch-Lees protein."} {"id": "PMID:179594", "title": "Hormone action at the membrane level. V. Binding of (+/-)-[3H]isoproterenol to intact chicken erythrocytes and erythrocyte ghosts.", "content": "The binding of (+/-)-[7-3H]isoproterenol to intact chicken erythrocytes has been investigated by a rapid centrifugation technique. The binding is displaceable by a one thousand-fold excess of cold isoproterenol and consists of two fractions, only one of which is inhibitable by the beta antagonist (--)-propranolol. The total displaceable binding to intact cells amounts to 80 or 127 molecules per cell at a (+/-)-isoproterenol concentration of 0.4 muM depending on the method employed to analyze the binding. Under similar conditions, the total displaceable binding to isolated membrane ghosts is 12600 molecules per cell. The propranolol-inhibitable binding to intact cell reaches saturation within 5 min at 4 degrees C and gives by scatchard analysis a maximum binding of 108 molecules per cell and with a KD of 0.4 muM. 50% inhibition of binding is obtained with 0.3 muM unlabeled (--)-isoproterenol as compared to 20 muM unlabeled (+)-isoproterenol. The binding of isoproterenol thus shows a marked stereospecific preference for the (--)-isomer.", "contents": "Hormone action at the membrane level. V. Binding of (+/-)-[3H]isoproterenol to intact chicken erythrocytes and erythrocyte ghosts. The binding of (+/-)-[7-3H]isoproterenol to intact chicken erythrocytes has been investigated by a rapid centrifugation technique. The binding is displaceable by a one thousand-fold excess of cold isoproterenol and consists of two fractions, only one of which is inhibitable by the beta antagonist (--)-propranolol. The total displaceable binding to intact cells amounts to 80 or 127 molecules per cell at a (+/-)-isoproterenol concentration of 0.4 muM depending on the method employed to analyze the binding. Under similar conditions, the total displaceable binding to isolated membrane ghosts is 12600 molecules per cell. The propranolol-inhibitable binding to intact cell reaches saturation within 5 min at 4 degrees C and gives by scatchard analysis a maximum binding of 108 molecules per cell and with a KD of 0.4 muM. 50% inhibition of binding is obtained with 0.3 muM unlabeled (--)-isoproterenol as compared to 20 muM unlabeled (+)-isoproterenol. The binding of isoproterenol thus shows a marked stereospecific preference for the (--)-isomer."} {"id": "PMID:179595", "title": "Interactions of the cholesterol side-chain with egg lecithin. A spin label study.", "content": "The effect in egg lecithin liposomes of cholesterol and cholesterol analogues with side-chains of reduced length on the order parameters of two steroid spin labels has been studied. Analogues with side-chains shorter than cholesterol by more than three carbon cause significantly less ordering than cholesterol. Liposomes containing a cholesterol analogue in which the side-chain is absent cause very little increase in the ordering of a new sterol spin label in which the nitroxide is incorporated into the side-chain. The results suggest that the sterol side-chain exerts a great influence on membrane rigidity within its immediate environment.", "contents": "Interactions of the cholesterol side-chain with egg lecithin. A spin label study. The effect in egg lecithin liposomes of cholesterol and cholesterol analogues with side-chains of reduced length on the order parameters of two steroid spin labels has been studied. Analogues with side-chains shorter than cholesterol by more than three carbon cause significantly less ordering than cholesterol. Liposomes containing a cholesterol analogue in which the side-chain is absent cause very little increase in the ordering of a new sterol spin label in which the nitroxide is incorporated into the side-chain. The results suggest that the sterol side-chain exerts a great influence on membrane rigidity within its immediate environment."} {"id": "PMID:179596", "title": "Cell surface and metabolic labelling of the proteins of normal and transformed chicken cells.", "content": "We have studied the surface proteins of normal and transformed chick cells using four-labelling techniques with different specificities, (a) lactoperoxidase catalysed iodination (b) galactose oxidase/B3H4 (c) pyridoxal phosphate/B3H4 and (d) periodate/B3H4. All methods labelled a large external transformation-sensitive (LETS) protein, in agreement with previous studies. In addition, using galactose oxidase and periodate labelling techniques, we present evidence which suggests that the transformed cell surface glycoproteins are more sialylated. The LETS protein was also labelled with (14C) glucosamine and after trypsinization a small band of identical molecular weight to LETS remained, possibly representing an internal pool of the protein. In contrast LETS protein labelled with (3H) fucose was completely removed by trypsin, suggesting that the internal pool of the protein is incompletely glycosylated. Evidence is also presented to show that although the level of the protein is drastically reduced at the transformed cell surface, it is still synthesised and shed into the medium.", "contents": "Cell surface and metabolic labelling of the proteins of normal and transformed chicken cells. We have studied the surface proteins of normal and transformed chick cells using four-labelling techniques with different specificities, (a) lactoperoxidase catalysed iodination (b) galactose oxidase/B3H4 (c) pyridoxal phosphate/B3H4 and (d) periodate/B3H4. All methods labelled a large external transformation-sensitive (LETS) protein, in agreement with previous studies. In addition, using galactose oxidase and periodate labelling techniques, we present evidence which suggests that the transformed cell surface glycoproteins are more sialylated. The LETS protein was also labelled with (14C) glucosamine and after trypsinization a small band of identical molecular weight to LETS remained, possibly representing an internal pool of the protein. In contrast LETS protein labelled with (3H) fucose was completely removed by trypsin, suggesting that the internal pool of the protein is incompletely glycosylated. Evidence is also presented to show that although the level of the protein is drastically reduced at the transformed cell surface, it is still synthesised and shed into the medium."} {"id": "PMID:179597", "title": "Localization of enzymes in specialized regions of the microsomal membrane.", "content": "Microsomal vesicles were centrifuged through sucrose density gradients containing deoxycholate. With 0.15% detergent electron transport enzymes and phosphatases could be separated. Increasing the deoxycholate concentration to 0.19% resulted in separation of the microsomal material into five bands containing (in order from the top of the gradient) adenosine monophosphatase, inosine diphosphatase and some glucose-6-phosphatase (band 1); NADH-linked (band 2) and NADH-linked (band 3) electron transport enzymes; and glucose-6-phosphatase (bands 4 and 5). It appears that enzymes are arranged in specialized patches in the microsomal membrane.", "contents": "Localization of enzymes in specialized regions of the microsomal membrane. Microsomal vesicles were centrifuged through sucrose density gradients containing deoxycholate. With 0.15% detergent electron transport enzymes and phosphatases could be separated. Increasing the deoxycholate concentration to 0.19% resulted in separation of the microsomal material into five bands containing (in order from the top of the gradient) adenosine monophosphatase, inosine diphosphatase and some glucose-6-phosphatase (band 1); NADH-linked (band 2) and NADH-linked (band 3) electron transport enzymes; and glucose-6-phosphatase (bands 4 and 5). It appears that enzymes are arranged in specialized patches in the microsomal membrane."} {"id": "PMID:179598", "title": "The glucagon receptor of rat liver plasma membrane can couple to adenylate cyclase without activating it.", "content": "1. Activation of adenylate cyclase in rat liver plasma membranes by fluoride or GMP-P (NH)P yielded linear Arrheniun plots. Activation by glucagon alone, or in combination with either fluoride or GMP-P(NH)P resulted in biphasic Arrhenius plots with a well-defined break at 28.5 +/- 1 degrees C. 2. The competitive glucagon antagonist, des-His-glucagon did not activate the adenylate cyclase but produced biphasic Arrhenius plots in combination with fluoride or GMP-P(NH)P. The break temperatures and activation energies were very similar to those observed with glucagon alone, or in combination with either fluoride or GMP-P(NH)P. 3. It is concluded that although des-His-glucagon is a potent antagonist of glucagon, it nevertheless causes a structural coupling between the receptor and the catalytic unit.", "contents": "The glucagon receptor of rat liver plasma membrane can couple to adenylate cyclase without activating it. 1. Activation of adenylate cyclase in rat liver plasma membranes by fluoride or GMP-P (NH)P yielded linear Arrheniun plots. Activation by glucagon alone, or in combination with either fluoride or GMP-P(NH)P resulted in biphasic Arrhenius plots with a well-defined break at 28.5 +/- 1 degrees C. 2. The competitive glucagon antagonist, des-His-glucagon did not activate the adenylate cyclase but produced biphasic Arrhenius plots in combination with fluoride or GMP-P(NH)P. The break temperatures and activation energies were very similar to those observed with glucagon alone, or in combination with either fluoride or GMP-P(NH)P. 3. It is concluded that although des-His-glucagon is a potent antagonist of glucagon, it nevertheless causes a structural coupling between the receptor and the catalytic unit."} {"id": "PMID:179599", "title": "The lipid environment of the glucagon receptor regulates adenylate cyclase activity.", "content": "1. The lipids composition of rat liver plasma membranes was substantially altered by introducing synthetic phosphatidylcholines into the membrane by the techniques of lipid substitution or lipid fusion. 40-60% of the total lipid pool in the modified membranes consisted of a synthetic phosphatidylcholine. 2. Lipid substitution, using cholate to equilibrate the lipid pools, resulted in the irreversible loss of a major part of the adenylate cyclase activity stimulated by F-, GMP-P(NH)P or glucagon. However, fusion with presonicated vesicles of the synethic phosphatidylcholines causes only small losses in adenylate cyclase activity stimulated by the same ligands. 3. The linear form of the Arrhenius plots of adenylate cyclase activity stimulated by F- or GMP-(NH)P was unaltered in all of the membrane preparations modified by substitution or fusion, with very similar activation energies to those observed with the native membrane. The activity of the enzyme therefore appears to be very insensitive to its lipid environment when stimulated by F- or gmp-p(nh)p. 4. in contrast, the break at 28.5 degrees C in the Arrhenius plot of adenylate cyclase activity stimulated by glucagon in the native membrane, was shifted upwards by dipalmitoyl phosphatidylcholine, downwards by dimyristoyl phosphatidylcholine, and was abolished by dioleoyl phosphatidylcholine. Very similar shifts in the break point were observed for stimulation by glucagon or des-His-glucagon in combination with F- or GMP-P(NH)P. The break temperatures and activation energies for adenylate cyclase activity were the same in complexes prepared with a phosphatidylcholine by fusion or substitution. 5. The breaks in the Arrhenius plots of adenylate cyclase activity are attributed to lipid phase separations which are shifted in the modified membranes according to the transition temperature of the synthetic phosphatidylcholine. Coupling the receptor to the enzyme by glucagon or des-His-glucagon renders the enzyme sensitive to the lipid environment of the receptor. Spin-label experiments support this interpretation and suggest that the lipid phase separation at 28.5 degrees C in the native membrane may only occur in one half of the bilayer.", "contents": "The lipid environment of the glucagon receptor regulates adenylate cyclase activity. 1. The lipids composition of rat liver plasma membranes was substantially altered by introducing synthetic phosphatidylcholines into the membrane by the techniques of lipid substitution or lipid fusion. 40-60% of the total lipid pool in the modified membranes consisted of a synthetic phosphatidylcholine. 2. Lipid substitution, using cholate to equilibrate the lipid pools, resulted in the irreversible loss of a major part of the adenylate cyclase activity stimulated by F-, GMP-P(NH)P or glucagon. However, fusion with presonicated vesicles of the synethic phosphatidylcholines causes only small losses in adenylate cyclase activity stimulated by the same ligands. 3. The linear form of the Arrhenius plots of adenylate cyclase activity stimulated by F- or GMP-(NH)P was unaltered in all of the membrane preparations modified by substitution or fusion, with very similar activation energies to those observed with the native membrane. The activity of the enzyme therefore appears to be very insensitive to its lipid environment when stimulated by F- or gmp-p(nh)p. 4. in contrast, the break at 28.5 degrees C in the Arrhenius plot of adenylate cyclase activity stimulated by glucagon in the native membrane, was shifted upwards by dipalmitoyl phosphatidylcholine, downwards by dimyristoyl phosphatidylcholine, and was abolished by dioleoyl phosphatidylcholine. Very similar shifts in the break point were observed for stimulation by glucagon or des-His-glucagon in combination with F- or GMP-P(NH)P. The break temperatures and activation energies for adenylate cyclase activity were the same in complexes prepared with a phosphatidylcholine by fusion or substitution. 5. The breaks in the Arrhenius plots of adenylate cyclase activity are attributed to lipid phase separations which are shifted in the modified membranes according to the transition temperature of the synthetic phosphatidylcholine. Coupling the receptor to the enzyme by glucagon or des-His-glucagon renders the enzyme sensitive to the lipid environment of the receptor. Spin-label experiments support this interpretation and suggest that the lipid phase separation at 28.5 degrees C in the native membrane may only occur in one half of the bilayer."} {"id": "PMID:179600", "title": "[Study, by an enzymatic method, of the isomers of L-proline (3H-4) and of the effects of preservation].", "content": "By use of procollagen proline hydroxylas which catalyses the substitution of the hydrogen in the trans position on carbon 4 with an hydroxyl on L-proline residues of procollagen, we have shown that the L-[3H-4] proline product of C.E.N. Saclay contained 29 per cent of the trans and 71 per cent of the cis form. It was also possible to verify the molecular stability of the isomers and that a small amount of tritium was randomly linked to the whole molecule.", "contents": "[Study, by an enzymatic method, of the isomers of L-proline (3H-4) and of the effects of preservation]. By use of procollagen proline hydroxylas which catalyses the substitution of the hydrogen in the trans position on carbon 4 with an hydroxyl on L-proline residues of procollagen, we have shown that the L-[3H-4] proline product of C.E.N. Saclay contained 29 per cent of the trans and 71 per cent of the cis form. It was also possible to verify the molecular stability of the isomers and that a small amount of tritium was randomly linked to the whole molecule."} {"id": "PMID:179601", "title": "[The action of calcium on the step of collagen metabolism, catalyzed by procollagen-proline hydroxylase].", "content": "Calcium effects on procollagen-proline-hydroxylase activity of chick embryo tibias was studied. Serial preincubation of the natural substrate, the enzymatic preparation or the mixture of both with and without calcium showed that calcium decreased procollagen-prolin-hydroxylase affinity for procollagen, decreased the maximum velocity of the reaction by binding to the substrate and by increasing the thermosensitivity of the enzyme -- substrate complex. Calcium could also increase the maximum velocity by dissociation of an enzyme -- inhibitor ligand complex. The resulting decrease of the overall reaction rate has been discussed in the context of the relationship between collagen metabolism and calcium fixation during calcification.", "contents": "[The action of calcium on the step of collagen metabolism, catalyzed by procollagen-proline hydroxylase]. Calcium effects on procollagen-proline-hydroxylase activity of chick embryo tibias was studied. Serial preincubation of the natural substrate, the enzymatic preparation or the mixture of both with and without calcium showed that calcium decreased procollagen-prolin-hydroxylase affinity for procollagen, decreased the maximum velocity of the reaction by binding to the substrate and by increasing the thermosensitivity of the enzyme -- substrate complex. Calcium could also increase the maximum velocity by dissociation of an enzyme -- inhibitor ligand complex. The resulting decrease of the overall reaction rate has been discussed in the context of the relationship between collagen metabolism and calcium fixation during calcification."} {"id": "PMID:179605", "title": "[Formation of adducts of pyridine nucleotides in the active center of swine lactate dehydrogenase (isoenzyme M4)].", "content": "Isozyme M4 of pig lactate dehydrogenase (LDH-M4) catalyzes reaction of NAD-adduct formation with a nucleophylic agent that is perhaps OH--ion. The T 1/2 of the reaction is 10-30 sec at concentration NAD 2,0-10(-3) M, LDH-M4 50 gamma/ml at pH greater than 8. Initial velocity and limit of the reaction increase at high LDH-M4, NAD and OH--ion concentrations. Pyridine-3-aldehyde and 3-acetyl pyridine analogs of NAD forms fluorescent adducts too, but at OH--ion concentration approximately 0,01 of that in the case of NAD reaction. Isoelectrical point of LDH-M4 determined by isoelectrofocusing method is 8,65 +/- 0,04 pH unit.", "contents": "[Formation of adducts of pyridine nucleotides in the active center of swine lactate dehydrogenase (isoenzyme M4)]. Isozyme M4 of pig lactate dehydrogenase (LDH-M4) catalyzes reaction of NAD-adduct formation with a nucleophylic agent that is perhaps OH--ion. The T 1/2 of the reaction is 10-30 sec at concentration NAD 2,0-10(-3) M, LDH-M4 50 gamma/ml at pH greater than 8. Initial velocity and limit of the reaction increase at high LDH-M4, NAD and OH--ion concentrations. Pyridine-3-aldehyde and 3-acetyl pyridine analogs of NAD forms fluorescent adducts too, but at OH--ion concentration approximately 0,01 of that in the case of NAD reaction. Isoelectrical point of LDH-M4 determined by isoelectrofocusing method is 8,65 +/- 0,04 pH unit."} {"id": "PMID:179606", "title": "[Pyridoxal kinase activity and pyridoxal-P concentration in mammalian tissues under normal and experimental conditions].", "content": "The activity and the distribution of pyridoxal kinase in rat and mouse tissues are studied. The data obtained testify the presence of a relative excess of pyridoxal kinase in all the organs studied, which probably causes a high rate of pyridoxalphosphate (PLP) biosynthesis under comparatively low vitamin B6 concentration. A correlation between the level of pyridoxal kinase activity and the content of PLP in rat brain and liver during ontogenesis is observed. The activity of pyridoxal kinase and the content of PLP are shown to be sharply increased in liver of rats received a protein-rich diet. Bilateral adrenalectomy resulted in the decrease of absolute and specific enzyme activities in rat liver by 20--30%. The content of PLP in mouse brain and liver was sharply decreased under experimental B6-avitaminosis while the content of pyridoxal kinase practically did not change. The injection of vitamin B6 rapidly normalized the PLP content in mouse tissues. The data obtained show that under physiological conditions the functional activity of pyridoxal kinase may be regulated in tissues by enzyme and substate contents. Some aspects of vitamin B6 metabolism in mammals are considered. It is concluded that in body the pyridoxal catabolism connected with its phosphorylation by pyridoxal kinase and the formation of pyridoxalphosphate.", "contents": "[Pyridoxal kinase activity and pyridoxal-P concentration in mammalian tissues under normal and experimental conditions]. The activity and the distribution of pyridoxal kinase in rat and mouse tissues are studied. The data obtained testify the presence of a relative excess of pyridoxal kinase in all the organs studied, which probably causes a high rate of pyridoxalphosphate (PLP) biosynthesis under comparatively low vitamin B6 concentration. A correlation between the level of pyridoxal kinase activity and the content of PLP in rat brain and liver during ontogenesis is observed. The activity of pyridoxal kinase and the content of PLP are shown to be sharply increased in liver of rats received a protein-rich diet. Bilateral adrenalectomy resulted in the decrease of absolute and specific enzyme activities in rat liver by 20--30%. The content of PLP in mouse brain and liver was sharply decreased under experimental B6-avitaminosis while the content of pyridoxal kinase practically did not change. The injection of vitamin B6 rapidly normalized the PLP content in mouse tissues. The data obtained show that under physiological conditions the functional activity of pyridoxal kinase may be regulated in tissues by enzyme and substate contents. Some aspects of vitamin B6 metabolism in mammals are considered. It is concluded that in body the pyridoxal catabolism connected with its phosphorylation by pyridoxal kinase and the formation of pyridoxalphosphate."} {"id": "PMID:179607", "title": "[Adrenal cortex cytochrome c].", "content": "The method of preparation of highly purified cytochrome c from bovine adrenal cortex is described. Absolute spectra of the protein in reduced and oxidized states and some its physico-chemical properties are investigated.", "contents": "[Adrenal cortex cytochrome c]. The method of preparation of highly purified cytochrome c from bovine adrenal cortex is described. Absolute spectra of the protein in reduced and oxidized states and some its physico-chemical properties are investigated."} {"id": "PMID:179608", "title": "[Distribution and activity of pyridoxal kinase in human brain during ontogenesis].", "content": "The activity of pyridoxal kinase was sharply increased in whole brain tissue of human, embryos and fetuses within 6-11 weeks of development. In brain stem the maximal values of the enzyme activity was observed at early stages of prenatal development of fetuses. The activity of pyridoxal kinase was increased in cerebral cortex and in the limbic system up to complete maturation of fetuses. It correlated with the fetus age within 14-40 weeks of development as calculated per 1 g of tissue wight or 1 mg of protein. The enzyme is distributed evenly in brain of newborns, babies and adult people. Its activity in grey cortex substance is higher, than in white one. There are 2-10-fold individual fluctuations of pyridoxal kinase activity in brain of people without CNS pathology. In newborns, having prolonged hypoxy at prenatal period, the enzyme activity was on the average by 70-80% lower at different brain parts than in newborns which had no primary asphyxia. A low pyridoxal kinase activity (not more than 1-5% as compared with its normal level) was observed in different brain parts of a child affected by focal gliosis and epilepsy.", "contents": "[Distribution and activity of pyridoxal kinase in human brain during ontogenesis]. The activity of pyridoxal kinase was sharply increased in whole brain tissue of human, embryos and fetuses within 6-11 weeks of development. In brain stem the maximal values of the enzyme activity was observed at early stages of prenatal development of fetuses. The activity of pyridoxal kinase was increased in cerebral cortex and in the limbic system up to complete maturation of fetuses. It correlated with the fetus age within 14-40 weeks of development as calculated per 1 g of tissue wight or 1 mg of protein. The enzyme is distributed evenly in brain of newborns, babies and adult people. Its activity in grey cortex substance is higher, than in white one. There are 2-10-fold individual fluctuations of pyridoxal kinase activity in brain of people without CNS pathology. In newborns, having prolonged hypoxy at prenatal period, the enzyme activity was on the average by 70-80% lower at different brain parts than in newborns which had no primary asphyxia. A low pyridoxal kinase activity (not more than 1-5% as compared with its normal level) was observed in different brain parts of a child affected by focal gliosis and epilepsy."} {"id": "PMID:179609", "title": "[The interaction of pyridine-adenine-dinucleotides containing a hydrazide group with swine muscle lactate dehydrogenase].", "content": "Hydrazide group of 4-substituted NAD analogues is shown to interact with functional groups of substrate-binding site in double complexes with pig muscle lactate dehydrogenase (isoenzyme M4). The lactic acid residue, which is structurally incorporated into NAD analogue, improves slightly the binding of dinucleotide, while 2,2,6,6-tetramethylpiperidine-1-oxyl residue considerably decreases the firmless of binding. The comparison of the inhibitory ability of oxamate, incotinic acid hydraxide and their spin-labelled derivatives indicates the restricted and stiff sizes of a substrate-binding site.", "contents": "[The interaction of pyridine-adenine-dinucleotides containing a hydrazide group with swine muscle lactate dehydrogenase]. Hydrazide group of 4-substituted NAD analogues is shown to interact with functional groups of substrate-binding site in double complexes with pig muscle lactate dehydrogenase (isoenzyme M4). The lactic acid residue, which is structurally incorporated into NAD analogue, improves slightly the binding of dinucleotide, while 2,2,6,6-tetramethylpiperidine-1-oxyl residue considerably decreases the firmless of binding. The comparison of the inhibitory ability of oxamate, incotinic acid hydraxide and their spin-labelled derivatives indicates the restricted and stiff sizes of a substrate-binding site."} {"id": "PMID:179610", "title": "[Kinetics and regulatory properties of the disulfide reductase enzyme from mouse liver].", "content": "Disulfide reductase (DSR) of mice liver supernatant is kinetically demonstrated as associating-dissociating oligomeric protein with positive homotropic cooperativity for the substrate. Cyclic 3',5'-AMP (10(-11)--10(-5) M) activates DSR and increases V, but does not change either [S]0,5, nor nH and does not shift the plot of specific activity versus the enzyme concentration. ATP, GTP, UTP, CTP, protamine, histone, Mg2+, Ca2+, EDTA (but not adenosine, 5'-AMP, 2'3'-AMP, ADP beef serum albumin) activated DSR. The effects of different modifiers are not summed up. Preincubation is essential for the action of the majority of the activators. Heating for 8 minutes at 55 degrees C desensitized completely DSR to all the modifiers without changing its catalytic activity, [S]0,5 and nH values. Possible mechanisms of activation of DSR, especially the involvement of protein kinase, are discussed.", "contents": "[Kinetics and regulatory properties of the disulfide reductase enzyme from mouse liver]. Disulfide reductase (DSR) of mice liver supernatant is kinetically demonstrated as associating-dissociating oligomeric protein with positive homotropic cooperativity for the substrate. Cyclic 3',5'-AMP (10(-11)--10(-5) M) activates DSR and increases V, but does not change either [S]0,5, nor nH and does not shift the plot of specific activity versus the enzyme concentration. ATP, GTP, UTP, CTP, protamine, histone, Mg2+, Ca2+, EDTA (but not adenosine, 5'-AMP, 2'3'-AMP, ADP beef serum albumin) activated DSR. The effects of different modifiers are not summed up. Preincubation is essential for the action of the majority of the activators. Heating for 8 minutes at 55 degrees C desensitized completely DSR to all the modifiers without changing its catalytic activity, [S]0,5 and nH values. Possible mechanisms of activation of DSR, especially the involvement of protein kinase, are discussed."} {"id": "PMID:179611", "title": "[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas].", "content": "N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP.", "contents": "[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas]. N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP."} {"id": "PMID:179612", "title": "[The possible role of high molecular weight polyphosphates in chlortetracycline biosynthesis by Streptomyces aureofaciens].", "content": "The content of condensed inorganic polyphosphates in high productive and low productive Streptomyces aureofaciens strains has been determined. At all the stages of growing the quantity of these compounds in low productive strain is 8-10-fold higher than in high productive strains. Maximum accumulation of condensed inorganic polyphosphates in both the strains Str. aureofaciens corresponds to the end of logarithmic phase of growth. In both strains the presence of two enzymes of polyphosphate biosynthesis -- ATP:polyphosphate-phosphotransferase and 1.3-diphosphoglycerate:polyphosphate-phosphotransferase has been revealed as well as the presence of the enzymes of their utilisation -- polyphosphate:D-glucose-6-phosphotransferase, polyphosphate-phosphohydrolase, tripolyphosphosphate-phosphohydrolase and pyrophosphate-phosphohydrolase. The difference in the activity of 1.3 diphosphoglycerate: polyphosphate-phosphotransferase and polyphosphate-phosphohydrolase has been revealed in both strains studied. On the basis of the data obtained it is supposed that there is a possibility of using phosphorus and energy of high molecular inorganic polyphosphate in the biosynthesis of so called products of \"secondary metabolism\".", "contents": "[The possible role of high molecular weight polyphosphates in chlortetracycline biosynthesis by Streptomyces aureofaciens]. The content of condensed inorganic polyphosphates in high productive and low productive Streptomyces aureofaciens strains has been determined. At all the stages of growing the quantity of these compounds in low productive strain is 8-10-fold higher than in high productive strains. Maximum accumulation of condensed inorganic polyphosphates in both the strains Str. aureofaciens corresponds to the end of logarithmic phase of growth. In both strains the presence of two enzymes of polyphosphate biosynthesis -- ATP:polyphosphate-phosphotransferase and 1.3-diphosphoglycerate:polyphosphate-phosphotransferase has been revealed as well as the presence of the enzymes of their utilisation -- polyphosphate:D-glucose-6-phosphotransferase, polyphosphate-phosphohydrolase, tripolyphosphosphate-phosphohydrolase and pyrophosphate-phosphohydrolase. The difference in the activity of 1.3 diphosphoglycerate: polyphosphate-phosphotransferase and polyphosphate-phosphohydrolase has been revealed in both strains studied. On the basis of the data obtained it is supposed that there is a possibility of using phosphorus and energy of high molecular inorganic polyphosphate in the biosynthesis of so called products of \"secondary metabolism\"."} {"id": "PMID:179613", "title": "[Escherichia coli membrane-bound polyphosphatase].", "content": "A complex of polyphosphatase with E. coli membranes has been isolated and studied. It is shown by gel-filtration through G-200 Sephadex and centrifugation in sucrose concentration gradient that about 5% of polyphosphatase total content in cells is bound with the heterogenous fraction containing smooth membranes and the ribosome-membrane complex. On the basis of the data obtained it is suggested that the formation of a complex of polyphosphatase with membranes is a stage of synthesis and secretion of this enzyme to protoplasm.", "contents": "[Escherichia coli membrane-bound polyphosphatase]. A complex of polyphosphatase with E. coli membranes has been isolated and studied. It is shown by gel-filtration through G-200 Sephadex and centrifugation in sucrose concentration gradient that about 5% of polyphosphatase total content in cells is bound with the heterogenous fraction containing smooth membranes and the ribosome-membrane complex. On the basis of the data obtained it is suggested that the formation of a complex of polyphosphatase with membranes is a stage of synthesis and secretion of this enzyme to protoplasm."} {"id": "PMID:179614", "title": "[Changes in mitochondrial heterogenicity during aerobic growth of Saccharomyces cerevisiae yeasts].", "content": "Distribution of the activities of some mitochondrial enzymes after sucrose density gradient ultracentrifugation of cell homogenates of S. cerevisiae in the early and late exponential growth phases is studied. It is demonstrated that young yeast cells have a characteristic complex distribution of NADH oxidase (cyanide-sensitive), succinate:ferricyanide-oxidoreductase (or succinate:2,6-dichlorophenol indophenol-oxidoreductase), NADH:2,6-dichlorophenol indophenol-oxidoreductase and cytochrome oxidase activities in sucrose density gradient; the distribution patterns of these activities are different. All the above activities are detected in a single relatively narrow band in mature yeast cells. Similar results are obtained in the experiments with glucose or galactose as a carbon source in the yeast growth media. The Arrhenius plots for NADH oxidase (as well as for succinate:2,6-dichlorophenol indophenol-oxidoreductase) activity do not differ in the case of \"light\" and \"heavy\" mitochondrial structures characteristic of yeast cells in the early exponential growth phase. Nevertheless, \"light\" and \"heavy\" mitochondrial structures differ with respect of the arrangement of certain respiratory chain components in their membranes NADH-dehydrogenase and cytochrome oxidase). This conclusion is drawn from the results obtained in the study of the interaction of the two types of structures with Fe(CN)6(3-), a non-penetrating ion and the antiserum to yeast mitochondria.", "contents": "[Changes in mitochondrial heterogenicity during aerobic growth of Saccharomyces cerevisiae yeasts]. Distribution of the activities of some mitochondrial enzymes after sucrose density gradient ultracentrifugation of cell homogenates of S. cerevisiae in the early and late exponential growth phases is studied. It is demonstrated that young yeast cells have a characteristic complex distribution of NADH oxidase (cyanide-sensitive), succinate:ferricyanide-oxidoreductase (or succinate:2,6-dichlorophenol indophenol-oxidoreductase), NADH:2,6-dichlorophenol indophenol-oxidoreductase and cytochrome oxidase activities in sucrose density gradient; the distribution patterns of these activities are different. All the above activities are detected in a single relatively narrow band in mature yeast cells. Similar results are obtained in the experiments with glucose or galactose as a carbon source in the yeast growth media. The Arrhenius plots for NADH oxidase (as well as for succinate:2,6-dichlorophenol indophenol-oxidoreductase) activity do not differ in the case of \"light\" and \"heavy\" mitochondrial structures characteristic of yeast cells in the early exponential growth phase. Nevertheless, \"light\" and \"heavy\" mitochondrial structures differ with respect of the arrangement of certain respiratory chain components in their membranes NADH-dehydrogenase and cytochrome oxidase). This conclusion is drawn from the results obtained in the study of the interaction of the two types of structures with Fe(CN)6(3-), a non-penetrating ion and the antiserum to yeast mitochondria."} {"id": "PMID:179615", "title": "[Interaction of adenosin-3',5'-cyclosulfate with adenosine-3'5'-cyclophosphate dependent protein kinase and phosphodiesterase].", "content": "Interaction of adenosine-3',5'-cyclosulphate (cAMS) cAMP analogue, having sulphur atom instead of phosphorus in a six-term cyclic system with pig brain proteinkinase and rabbit skeletal muscle phosphodiesterase is studied. The affinity of proteinkinase to cAMS was found to be in 25000 times lower than the affinity of cAMP, the affinity of cAMS to the active site of phosphodiesterase being high enough. It is suggested that in the regulatory subunit of proteinkinase positive kationic group participates in nucleotide binding by interacting with negative oxygen atom of six-term cyclophosphate system. There is no such a group in the active site of phospodiesterase, because the absence of negative charge in case of cAMS only slightly affects the constant of cAMS binding by phosphodiesterase.", "contents": "[Interaction of adenosin-3',5'-cyclosulfate with adenosine-3'5'-cyclophosphate dependent protein kinase and phosphodiesterase]. Interaction of adenosine-3',5'-cyclosulphate (cAMS) cAMP analogue, having sulphur atom instead of phosphorus in a six-term cyclic system with pig brain proteinkinase and rabbit skeletal muscle phosphodiesterase is studied. The affinity of proteinkinase to cAMS was found to be in 25000 times lower than the affinity of cAMP, the affinity of cAMS to the active site of phosphodiesterase being high enough. It is suggested that in the regulatory subunit of proteinkinase positive kationic group participates in nucleotide binding by interacting with negative oxygen atom of six-term cyclophosphate system. There is no such a group in the active site of phospodiesterase, because the absence of negative charge in case of cAMS only slightly affects the constant of cAMS binding by phosphodiesterase."} {"id": "PMID:179616", "title": "[Potentiation of ACTH action by a fragment of it: a decrease in the rat adrenal ascorbic acid concentration in vivo].", "content": "The effect of tripeptide NH2CO-Arg-Pro-Val-NH2, the analogue of common fragments of some peptide hormones and kinins, on the content of ascorbic acid in rat adrenal glands in vivo is studied. It is shown that the peptide (5 divided by 3000 mkg/100 g body weight) produces no effect on the content of ascorbic acid in adrenal glands, but its injection half an hour before the administration of native ACTH canses a significant increase in the ACTH activity. The peptide possesses the myotropic activity; it exerts sinergism and potentiation of the ACTH action on rat ascending colon.", "contents": "[Potentiation of ACTH action by a fragment of it: a decrease in the rat adrenal ascorbic acid concentration in vivo]. The effect of tripeptide NH2CO-Arg-Pro-Val-NH2, the analogue of common fragments of some peptide hormones and kinins, on the content of ascorbic acid in rat adrenal glands in vivo is studied. It is shown that the peptide (5 divided by 3000 mkg/100 g body weight) produces no effect on the content of ascorbic acid in adrenal glands, but its injection half an hour before the administration of native ACTH canses a significant increase in the ACTH activity. The peptide possesses the myotropic activity; it exerts sinergism and potentiation of the ACTH action on rat ascending colon."} {"id": "PMID:179617", "title": "[Use of snake venom immobilized phosphodiesterase for analysis of the nucleotide composition of oligodesoxyribonucleotides].", "content": "A simple one-step technique for the analysis of nucleotide composition of oligodeoxyribonucleotides is described. The method is based on enzymatic hydrolysis and subsequent separation of hydrolysate on a \"combined\" column with Aminex A 28 anionite, on which top immobilyzed on DEAE cellulose snake venom phosphodiesterase is layed. The method is tested using a number of synthetic di- and tri-deoxyribonucleotides.", "contents": "[Use of snake venom immobilized phosphodiesterase for analysis of the nucleotide composition of oligodesoxyribonucleotides]. A simple one-step technique for the analysis of nucleotide composition of oligodeoxyribonucleotides is described. The method is based on enzymatic hydrolysis and subsequent separation of hydrolysate on a \"combined\" column with Aminex A 28 anionite, on which top immobilyzed on DEAE cellulose snake venom phosphodiesterase is layed. The method is tested using a number of synthetic di- and tri-deoxyribonucleotides."} {"id": "PMID:179618", "title": "[Free radicals in the flavin reduction reaction. Interaction of reduced nicotinamide adenine dinucleotide with flavin in solution].", "content": "The study of the flavin mononucleotide (FMN)-reduced nicotinamide adeninedinucleotide (NADH) reaction was carried out both under aerobic and anaerobic conditions, using spectrophotometric and titrimetric methods. The consumption of NADH was shown to exceed two times the consumption of FMN in the anaerobic reaction and the rate constant in the aerobic reaction was found to be about 4 times of that of the anaerobic reaction. Moreover, the replacement of anaerobic conditions by aerobic ones at pH 5.0 resulted in a considerable increase of proton consumption rate in the reaction course. The data obtained are contradictory to the generally accepted hypothesis of hydrid-ion transfer in the reaction of NADH oxidation. It was assumed that this reaction proceeded through a homolytic pathway.", "contents": "[Free radicals in the flavin reduction reaction. Interaction of reduced nicotinamide adenine dinucleotide with flavin in solution]. The study of the flavin mononucleotide (FMN)-reduced nicotinamide adeninedinucleotide (NADH) reaction was carried out both under aerobic and anaerobic conditions, using spectrophotometric and titrimetric methods. The consumption of NADH was shown to exceed two times the consumption of FMN in the anaerobic reaction and the rate constant in the aerobic reaction was found to be about 4 times of that of the anaerobic reaction. Moreover, the replacement of anaerobic conditions by aerobic ones at pH 5.0 resulted in a considerable increase of proton consumption rate in the reaction course. The data obtained are contradictory to the generally accepted hypothesis of hydrid-ion transfer in the reaction of NADH oxidation. It was assumed that this reaction proceeded through a homolytic pathway."} {"id": "PMID:179619", "title": "[Myeloperoxidase synthesis in white mouse leukocytes].", "content": "H3-leucine incorporation in myeloperoxidase (MPO) and into total soluble protein (TSP) from leucocytes of peritoneal exudate of mice was determined by immunological procedure. Maximal H3-leucine incorporation was observed within 48 hours and 16 hours of exposition for MPO and TSP respectively. Half-life period of MPO was 2,6 days which is comparable with the duration of neutrophils maturation up to the stage of metamyelocyte. Apparently, no essential formation of MPO takes place at the level of band and segmented neutrophils.", "contents": "[Myeloperoxidase synthesis in white mouse leukocytes]. H3-leucine incorporation in myeloperoxidase (MPO) and into total soluble protein (TSP) from leucocytes of peritoneal exudate of mice was determined by immunological procedure. Maximal H3-leucine incorporation was observed within 48 hours and 16 hours of exposition for MPO and TSP respectively. Half-life period of MPO was 2,6 days which is comparable with the duration of neutrophils maturation up to the stage of metamyelocyte. Apparently, no essential formation of MPO takes place at the level of band and segmented neutrophils."} {"id": "PMID:179620", "title": "[Isolation and properties of carboxycathepsin (peptidyl-dipeptidase) from bovine lung tissue].", "content": "2200-fold purified homogenous preparation of carboxycathepsin (peptidyl-dipeptidase) is isolated from bovine lung. The enzyme isolated converts angiotensine I into angiotensine II and distroys bradikinin. It is active in neutral medium, is activated by chloride ion and is inhibited by EDTA and Middle Asian snakes venom. The molecular weight of the enzyme is 180 000-190 000 as estimated by means of polyacrylamide gel electrophoresis, its isoelectric point is 4.48-4.53. The comparison of properties and specificity of carboxycathepsin from bovine lung and kidney draws to the conclusion that both enzymes are identical.", "contents": "[Isolation and properties of carboxycathepsin (peptidyl-dipeptidase) from bovine lung tissue]. 2200-fold purified homogenous preparation of carboxycathepsin (peptidyl-dipeptidase) is isolated from bovine lung. The enzyme isolated converts angiotensine I into angiotensine II and distroys bradikinin. It is active in neutral medium, is activated by chloride ion and is inhibited by EDTA and Middle Asian snakes venom. The molecular weight of the enzyme is 180 000-190 000 as estimated by means of polyacrylamide gel electrophoresis, its isoelectric point is 4.48-4.53. The comparison of properties and specificity of carboxycathepsin from bovine lung and kidney draws to the conclusion that both enzymes are identical."} {"id": "PMID:179622", "title": "Factors influencing the lipolytic response of swine (Sus domesticus) adipose tissue: ontogeny.", "content": "Swine adipose tissue was not responsive to glucagon at any age and only marginally to adrenocorticotropin (ACTH). The latter response could be greatly magnified and the sensitivity increased by addition of theophylline (Theo). The maximal lipolytic activity (MAX) obtained with ACTH plus Theo was minimal in the newborn, greatly increased in young animals, and reduced during the growing period; however, the sensitivity did not change. The MAX for Theo (plus low epinephrine) yielded a pattern similar to ACTH, but the sensitivity changed (most sensitive in younger animals). The MAX and sensitivity obtained with dibutyryl cyclic adenosine monophosphate were not appreciably changed during development.", "contents": "Factors influencing the lipolytic response of swine (Sus domesticus) adipose tissue: ontogeny. Swine adipose tissue was not responsive to glucagon at any age and only marginally to adrenocorticotropin (ACTH). The latter response could be greatly magnified and the sensitivity increased by addition of theophylline (Theo). The maximal lipolytic activity (MAX) obtained with ACTH plus Theo was minimal in the newborn, greatly increased in young animals, and reduced during the growing period; however, the sensitivity did not change. The MAX for Theo (plus low epinephrine) yielded a pattern similar to ACTH, but the sensitivity changed (most sensitive in younger animals). The MAX and sensitivity obtained with dibutyryl cyclic adenosine monophosphate were not appreciably changed during development."} {"id": "PMID:179623", "title": "Development of gluconeogenic enzymes in the newborn guinea pig.", "content": "The activities of key gluconeogenic enzymes in the liver of newborn guinea pigs delivered vaginally at term were monitored as a function of time following birth. The activities of glucose-6-phosphatase and fructose-1,6-diphosphatase did not show a significant increase over the first 72 h of life, neither did the activity of mitochondrial phosphoenolpyruvate carboxykinase. The mitochondrial enzyme pyruvate carboxylase and the cytosolic phosphoenolpyruvate carboxykinase (PEPCK) both increased significantly in the first 24 h postpartum. Mitochondrial protein and succinate dehydrogenase activities showed only slight increases in the 72-hour period. Rapid depletion of liver glycogen was evident in these animals following birth, but severe hypoglycaemia was not evident. Mitochondrial and cytosolic PEPCK showed similar kinetic behaviour with respect to their affinities for oxalacetate and divalent metal cation Mn++, though the mitochondrial enzyme would accept Mg++ as the divalent metal in place of Mn++. The role of the compartmented PEPCK activities is discussed.", "contents": "Development of gluconeogenic enzymes in the newborn guinea pig. The activities of key gluconeogenic enzymes in the liver of newborn guinea pigs delivered vaginally at term were monitored as a function of time following birth. The activities of glucose-6-phosphatase and fructose-1,6-diphosphatase did not show a significant increase over the first 72 h of life, neither did the activity of mitochondrial phosphoenolpyruvate carboxykinase. The mitochondrial enzyme pyruvate carboxylase and the cytosolic phosphoenolpyruvate carboxykinase (PEPCK) both increased significantly in the first 24 h postpartum. Mitochondrial protein and succinate dehydrogenase activities showed only slight increases in the 72-hour period. Rapid depletion of liver glycogen was evident in these animals following birth, but severe hypoglycaemia was not evident. Mitochondrial and cytosolic PEPCK showed similar kinetic behaviour with respect to their affinities for oxalacetate and divalent metal cation Mn++, though the mitochondrial enzyme would accept Mg++ as the divalent metal in place of Mn++. The role of the compartmented PEPCK activities is discussed."} {"id": "PMID:179624", "title": "Ontogenic development of the responsiveness in cAMP synthesis to LH and PGE1 and gonadotropin receptors in the rat ovary.", "content": "Incubation of ovaries derived from rats aged 9, 13, 16, and 20 days with LH resulted in a significant rise in cAMP synthesis. The ovaries from 2- and 5-day-old rats were, however, unresponsive to stimulation by LH. By contrast, prostaglandin E1 (PGE1) evoked a sharp response in ovarian synthesis of cAMP even in 2-day-old rats. In order to determine why neonatal ovaries do not respond to LH, gonadotropic receptors have been studied. HCG binding sites were present in homogenates of untreated and gonadotropins primed rat ovaries. The specificity of this 125I-HCG binding was demonstrated by the competition of unlabeled HCG and LH for binding sites and failure of such binding to occur in specimens obtained from control tissues. FSH, ACTH and growth hormone were not able to compete significantly for 125I-HCG binding. The HCG receptor is present in ovaries during the whole postnatal period. The results suggest that the unresponsiveness of neonatal rat ovaries to LH is not caused by later maturation of gonadotropic receptors.", "contents": "Ontogenic development of the responsiveness in cAMP synthesis to LH and PGE1 and gonadotropin receptors in the rat ovary. Incubation of ovaries derived from rats aged 9, 13, 16, and 20 days with LH resulted in a significant rise in cAMP synthesis. The ovaries from 2- and 5-day-old rats were, however, unresponsive to stimulation by LH. By contrast, prostaglandin E1 (PGE1) evoked a sharp response in ovarian synthesis of cAMP even in 2-day-old rats. In order to determine why neonatal ovaries do not respond to LH, gonadotropic receptors have been studied. HCG binding sites were present in homogenates of untreated and gonadotropins primed rat ovaries. The specificity of this 125I-HCG binding was demonstrated by the competition of unlabeled HCG and LH for binding sites and failure of such binding to occur in specimens obtained from control tissues. FSH, ACTH and growth hormone were not able to compete significantly for 125I-HCG binding. The HCG receptor is present in ovaries during the whole postnatal period. The results suggest that the unresponsiveness of neonatal rat ovaries to LH is not caused by later maturation of gonadotropic receptors."} {"id": "PMID:179625", "title": "Recovery sleep following different visual conditions during total sleep deprivation in man.", "content": "The findings of visual impairment during total sleep deprivation were used as a basis for a possible link between vision and sleep. It was proposed that the level of visual load imposed during sleep deprivation was an important variable, and would have a substantial effect upon recovery sleep. Six young male subjects underwent two conditions of 64 h of sleep deprivation on separate occasions. One condition incorporated a high visual load, and the other a low load. Exercise and sound were balanced. All night sleep EEGs were taken for two baseline nights, and also for two recovery nights following each condition. There was a significant increase of stage 4 on all recovery nights and a REM rebound on the second recovery night. SWS, particularly stage 4, TST and REM density, were significantly greater following the high load. Implications of these findings for sleep theories and for sleep deprivation research are discussed.", "contents": "Recovery sleep following different visual conditions during total sleep deprivation in man. The findings of visual impairment during total sleep deprivation were used as a basis for a possible link between vision and sleep. It was proposed that the level of visual load imposed during sleep deprivation was an important variable, and would have a substantial effect upon recovery sleep. Six young male subjects underwent two conditions of 64 h of sleep deprivation on separate occasions. One condition incorporated a high visual load, and the other a low load. Exercise and sound were balanced. All night sleep EEGs were taken for two baseline nights, and also for two recovery nights following each condition. There was a significant increase of stage 4 on all recovery nights and a REM rebound on the second recovery night. SWS, particularly stage 4, TST and REM density, were significantly greater following the high load. Implications of these findings for sleep theories and for sleep deprivation research are discussed."} {"id": "PMID:179628", "title": "Estimation of parameters for a model of transmitter release at synapses.", "content": "We consider models for the release of transmitter in response to nerve impulses, where it is assumed that quanta of transmitter are released from some of n sites, the probability of release from any site being p. It is assumed that the quantal size is either a constant or is distributed as a normal or a gamma variate. Observations on both spontaneous potentials and evoked potentials are used to obtain moment estimated of n and p. Large sample estimates of the standard errors of these estimates are given.", "contents": "Estimation of parameters for a model of transmitter release at synapses. We consider models for the release of transmitter in response to nerve impulses, where it is assumed that quanta of transmitter are released from some of n sites, the probability of release from any site being p. It is assumed that the quantal size is either a constant or is distributed as a normal or a gamma variate. Observations on both spontaneous potentials and evoked potentials are used to obtain moment estimated of n and p. Large sample estimates of the standard errors of these estimates are given."} {"id": "PMID:179629", "title": "Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma.", "content": "An Epstein-Barr virus (EBV)-negative lymphoblastoid cell line (LCL), BJA-B, was established from an African Burkitt's lymphoma (BL) which contained no detectable EBV DNA and did not express the EBV specified antigen EBNA, BJA-B cells grow in typically large, flat clumps. All carry surface-bound immunoglobulins, a B lymphocyte marker, and do not form rosettes with sheep erythrocytes. After infection of BJA-B cells by EBV the infected cells may produce either EBV-determined nuclear antigen (EBNA) or both EBNA and early antigen (EA), depending on the strain of EBV. The homogeneity of the BJA-B cell population with respect to immunological and isoenzyme markers and size suggests a clonal origin of the line. BJA-B is the first EBV-negative LCL established from an African Burkitt's lymphoma and demonstrates that an EBV-independent continuous B cell line can be established \"in vitro\" from other than leukemia or myeloma cells.", "contents": "Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma. An Epstein-Barr virus (EBV)-negative lymphoblastoid cell line (LCL), BJA-B, was established from an African Burkitt's lymphoma (BL) which contained no detectable EBV DNA and did not express the EBV specified antigen EBNA, BJA-B cells grow in typically large, flat clumps. All carry surface-bound immunoglobulins, a B lymphocyte marker, and do not form rosettes with sheep erythrocytes. After infection of BJA-B cells by EBV the infected cells may produce either EBV-determined nuclear antigen (EBNA) or both EBNA and early antigen (EA), depending on the strain of EBV. The homogeneity of the BJA-B cell population with respect to immunological and isoenzyme markers and size suggests a clonal origin of the line. BJA-B is the first EBV-negative LCL established from an African Burkitt's lymphoma and demonstrates that an EBV-independent continuous B cell line can be established \"in vitro\" from other than leukemia or myeloma cells."} {"id": "PMID:179630", "title": "Renal transplantation and viral infections. II. Results of follow-up studies.", "content": "13 renal transplant recipeints were submitted to virological survey over a period of about 10 months following transplantation. They were compared to a group of individuals who underwent no transplantation : 7 patients on chronic hemodialysis and 10 healthy blood donors. The renal transplant recipients, showed rises in titer of antibodies against various viral antigens. Nevertheless, no other viral elimination but that of cytomegalovirus and herpes simplex virus was detected in them. Renal trnasplant recipients show significantly more often rises in virus antibody titers than the other individuals, when time of survey is taken into account. Some of these rises appeared to be simultaneous. Their mechanism is under debate : analysis of special cases and observation of associated immunohematological abnormalities are strongly suggesting that in some situations, rises in titer of viral antibodies may occur without infection.", "contents": "Renal transplantation and viral infections. II. Results of follow-up studies. 13 renal transplant recipeints were submitted to virological survey over a period of about 10 months following transplantation. They were compared to a group of individuals who underwent no transplantation : 7 patients on chronic hemodialysis and 10 healthy blood donors. The renal transplant recipients, showed rises in titer of antibodies against various viral antigens. Nevertheless, no other viral elimination but that of cytomegalovirus and herpes simplex virus was detected in them. Renal trnasplant recipients show significantly more often rises in virus antibody titers than the other individuals, when time of survey is taken into account. Some of these rises appeared to be simultaneous. Their mechanism is under debate : analysis of special cases and observation of associated immunohematological abnormalities are strongly suggesting that in some situations, rises in titer of viral antibodies may occur without infection."} {"id": "PMID:179631", "title": "Alterations in membrane-associated particle distribution during antidiuretic challenge in frog urinary bladder epithelium.", "content": "Frog urinary bladder epithelium has been examined by freeze-fracture electron microscopy of preparations previously fixed by glutaraldehyde either at rest or during antidiuretic challenge. All the agonists tested were observed to induce membrane particle clustering in the A face of the apical plasma membrane of granular cells. This was the case for the natural hormone (hypophysical extracts) and its presumed cellular mediator, adenosine 3',5'-monophosphate. Particle clustering was observed both in the presence and in the absence of water net flow and is thus independent of these movements. Clusters were also observed during hydrosmotic challenge by hypertonic serosal media, a condition which depresses transepithelial sodium transport. No complementary patterns of these A face clusters could be found on the B face. The significance of these membrane-associated particle clusters is discussed in terms of membrane structure and function.", "contents": "Alterations in membrane-associated particle distribution during antidiuretic challenge in frog urinary bladder epithelium. Frog urinary bladder epithelium has been examined by freeze-fracture electron microscopy of preparations previously fixed by glutaraldehyde either at rest or during antidiuretic challenge. All the agonists tested were observed to induce membrane particle clustering in the A face of the apical plasma membrane of granular cells. This was the case for the natural hormone (hypophysical extracts) and its presumed cellular mediator, adenosine 3',5'-monophosphate. Particle clustering was observed both in the presence and in the absence of water net flow and is thus independent of these movements. Clusters were also observed during hydrosmotic challenge by hypertonic serosal media, a condition which depresses transepithelial sodium transport. No complementary patterns of these A face clusters could be found on the B face. The significance of these membrane-associated particle clusters is discussed in terms of membrane structure and function."} {"id": "PMID:179632", "title": "Changes in the restriction of molecular rotational diffusion of water-soluble spin labels during fatty acid starvation of yeast.", "content": "Yeast mutants lacking fatty acid synthetase activity (fas-) die when deprived of saturated fatty acid under conditions which are otherwise growth-supporting. The spin label technique is used to show that restriction of molecular rotational diffusion of spin label molecules dissolved in aqueous zones increases several fold under conditions of fatty acid starvation while the apparent physical state of cellular hydrocarbon zones remains essentially unchanged. We focus attention on the cellular aqueous interior as the potential site of alteration under selective starvation conditions. Correspondences exist between restriction of molecular motion of water soluble spin labels dissolved in the cell and loss of cell viability. The correspondences to changes in the molecular motion of hydrocarbon soluble spin labels are much less or are not detectable.", "contents": "Changes in the restriction of molecular rotational diffusion of water-soluble spin labels during fatty acid starvation of yeast. Yeast mutants lacking fatty acid synthetase activity (fas-) die when deprived of saturated fatty acid under conditions which are otherwise growth-supporting. The spin label technique is used to show that restriction of molecular rotational diffusion of spin label molecules dissolved in aqueous zones increases several fold under conditions of fatty acid starvation while the apparent physical state of cellular hydrocarbon zones remains essentially unchanged. We focus attention on the cellular aqueous interior as the potential site of alteration under selective starvation conditions. Correspondences exist between restriction of molecular motion of water soluble spin labels dissolved in the cell and loss of cell viability. The correspondences to changes in the molecular motion of hydrocarbon soluble spin labels are much less or are not detectable."} {"id": "PMID:179633", "title": "Intermolecular interactions of oxygenated sickle hemoglobin molecules in cells and cell-free solutions.", "content": "We have measured the intermolecular interactions of oxygenated sickle hemoglobin molecules in cells and in cell-free solutions, and have compared the results with similar data for liganded normal adult hemoglobin. The experiments involve the measurement of the spin-lattice relaxation time T1 of protons of solvent water molecules, as a function of an externally applied static magnetic field. From such data, one can derive a correlation time tauc, for each sample, which is a measure of the time taken for a hemoglobin molecule to randomize its orientation due to Brownian motion. Thus tauc is a measure of the freedom of rotational motion, on a molecular or microscopic level, of hemoglobin molecules. Intermolecular interactions will reduce this freedom of motion and lengthen tauc. We find that oxygenated sickle hemoglobin molecules have an additional intermolecular interaction not found for normal hemoglobin. This extra interaction is increased by the presence of either inorganic phosphate or diphosphoglycerate, and is greater for sickle hemoglobin within cells than in cell-free solutions. By comparing the present results with published data on the viscosity of oxygenated sickle and normal hemoglobin, we conclude that, at concentrations comparable to intracellular values, oxygenated sickle hemoglobin molecules form aggregates several tetramers in size. The possibility exists that these aggregates are the earliest stage of fiber formation itself, the physical basis of the sickling phenomena.", "contents": "Intermolecular interactions of oxygenated sickle hemoglobin molecules in cells and cell-free solutions. We have measured the intermolecular interactions of oxygenated sickle hemoglobin molecules in cells and in cell-free solutions, and have compared the results with similar data for liganded normal adult hemoglobin. The experiments involve the measurement of the spin-lattice relaxation time T1 of protons of solvent water molecules, as a function of an externally applied static magnetic field. From such data, one can derive a correlation time tauc, for each sample, which is a measure of the time taken for a hemoglobin molecule to randomize its orientation due to Brownian motion. Thus tauc is a measure of the freedom of rotational motion, on a molecular or microscopic level, of hemoglobin molecules. Intermolecular interactions will reduce this freedom of motion and lengthen tauc. We find that oxygenated sickle hemoglobin molecules have an additional intermolecular interaction not found for normal hemoglobin. This extra interaction is increased by the presence of either inorganic phosphate or diphosphoglycerate, and is greater for sickle hemoglobin within cells than in cell-free solutions. By comparing the present results with published data on the viscosity of oxygenated sickle and normal hemoglobin, we conclude that, at concentrations comparable to intracellular values, oxygenated sickle hemoglobin molecules form aggregates several tetramers in size. The possibility exists that these aggregates are the earliest stage of fiber formation itself, the physical basis of the sickling phenomena."} {"id": "PMID:179634", "title": "The production of foot-and-mouth disease virus from BHK 21 C 13 cells grown on the surface of glass spheres.", "content": "In view of the advantages which are associated with the use of the BHK monolayer cell for the production of foot-and-mouth disease (FMD) virus, a unit system using glass spheres was developed to grow BHK monolayer cells and to test the susceptibility of such cells to FMD virus. The yield of cells and their susceptibility compares favorably with GREEN BHK monolayer cells which have been grown in Roux bottles.", "contents": "The production of foot-and-mouth disease virus from BHK 21 C 13 cells grown on the surface of glass spheres. In view of the advantages which are associated with the use of the BHK monolayer cell for the production of foot-and-mouth disease (FMD) virus, a unit system using glass spheres was developed to grow BHK monolayer cells and to test the susceptibility of such cells to FMD virus. The yield of cells and their susceptibility compares favorably with GREEN BHK monolayer cells which have been grown in Roux bottles."} {"id": "PMID:179635", "title": "The production of foot-and-mouth disease virus from BHK 21 C 13 cells grown on the surface of DEAE sephadex A50 beads.", "content": "Methods are described which make possible the production of foot-and-mouth disease (FMD) virus from BHK 21 C13 monolayer cells which have been grown on the surface of serum coated DEAE Sephadex A50 beads. The yield of cells and their susceptibility to infection by FMD virus are equivalent to conventional Roux monolayer systems. The potential for the commercial application of the DEAE Sephadex A50 system is discussed in relation to other unit process monolayer systems and in particular to the system in which cells are cultured in a deep bed of small glass spheres.", "contents": "The production of foot-and-mouth disease virus from BHK 21 C 13 cells grown on the surface of DEAE sephadex A50 beads. Methods are described which make possible the production of foot-and-mouth disease (FMD) virus from BHK 21 C13 monolayer cells which have been grown on the surface of serum coated DEAE Sephadex A50 beads. The yield of cells and their susceptibility to infection by FMD virus are equivalent to conventional Roux monolayer systems. The potential for the commercial application of the DEAE Sephadex A50 system is discussed in relation to other unit process monolayer systems and in particular to the system in which cells are cultured in a deep bed of small glass spheres."} {"id": "PMID:179637", "title": "An etiologic and nosologic overview of craniosynostosis syndromes.", "content": "In the past, a great deal of confusion in the nosology of craniosynostosis syndromes has been apparent. Such syndromes should never be classified on the basis of which sutures are synostosed nor on the presence or absence of mental retardation. In this paper, they are classified on the basis of overall clinical similarity and genetic considerations. The findings in each syndrome, the genetic aspects and the problems in differential diagnosis are discussed. Disorders presented include the Kleeblattsch\u00e4del anomaly, Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, Saethre-Chotzen syndrome, Carpenter syndrome, Christian syndrome, Summitt syndrome, Baller-Gerold syndrome, Lowry syndrome, Gorlin-Chaudhry-Moss syndrome and three sporadic craniosynostosis syndromes. A discussion of spurious craniosynostosis syndrome entities is also presented.", "contents": "An etiologic and nosologic overview of craniosynostosis syndromes. In the past, a great deal of confusion in the nosology of craniosynostosis syndromes has been apparent. Such syndromes should never be classified on the basis of which sutures are synostosed nor on the presence or absence of mental retardation. In this paper, they are classified on the basis of overall clinical similarity and genetic considerations. The findings in each syndrome, the genetic aspects and the problems in differential diagnosis are discussed. Disorders presented include the Kleeblattsch\u00e4del anomaly, Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, Saethre-Chotzen syndrome, Carpenter syndrome, Christian syndrome, Summitt syndrome, Baller-Gerold syndrome, Lowry syndrome, Gorlin-Chaudhry-Moss syndrome and three sporadic craniosynostosis syndromes. A discussion of spurious craniosynostosis syndrome entities is also presented."} {"id": "PMID:179638", "title": "[Half-life of rabbit heart mitochondria under normal conditions and in experimental allergic lesions of the heart].", "content": "Half-life of mitochondrial proteins and cytochrome C of rabbit myocardium was determined with glycine-I-C14 and H3-5-aminolevulinic acid, respectively, as precursors. Half-life of mitochondrial proteins calculated from the curve of the gradual radioactivity decline was 14.4 days, and that of cytochrome C--11.8 days; reutilization of glycine-C14 in plastic metabolism did not exceed 20%. No difference from control was noticed in rabbits with an experimental allergic heart damage.", "contents": "[Half-life of rabbit heart mitochondria under normal conditions and in experimental allergic lesions of the heart]. Half-life of mitochondrial proteins and cytochrome C of rabbit myocardium was determined with glycine-I-C14 and H3-5-aminolevulinic acid, respectively, as precursors. Half-life of mitochondrial proteins calculated from the curve of the gradual radioactivity decline was 14.4 days, and that of cytochrome C--11.8 days; reutilization of glycine-C14 in plastic metabolism did not exceed 20%. No difference from control was noticed in rabbits with an experimental allergic heart damage."} {"id": "PMID:179639", "title": "[The biological role of estriol].", "content": "It was demonstrated on the uteri of women and guinea pigs that estriol (in vitro) possessed a marked affinity to the estradiol-binding system of human and guinea pig uteri; the activity of steroid-receptor interaction of estriol in vitro constituted 9.4% for guinea pigs and 17% for man in relation to the estradiol activity. Administration of estriol to guinea pigs in vivo in a dose of 0.25-0.5 mg led to a sharp reduction of the estradiol-binding capacity of the receptor system of the uterus. It is supposed that there existed a competitive relationship between estradiol and estriol for binding with the active centres of the receptor proteins of the uterus.", "contents": "[The biological role of estriol]. It was demonstrated on the uteri of women and guinea pigs that estriol (in vitro) possessed a marked affinity to the estradiol-binding system of human and guinea pig uteri; the activity of steroid-receptor interaction of estriol in vitro constituted 9.4% for guinea pigs and 17% for man in relation to the estradiol activity. Administration of estriol to guinea pigs in vivo in a dose of 0.25-0.5 mg led to a sharp reduction of the estradiol-binding capacity of the receptor system of the uterus. It is supposed that there existed a competitive relationship between estradiol and estriol for binding with the active centres of the receptor proteins of the uterus."} {"id": "PMID:179640", "title": "[Participation of the fibers of the lingual nerve in the transmission of mechanosensitive information from the tongue and oral cavity of the cat].", "content": "The role of the lingual nerve fibers in the transmission of mechanosensory information from the receptors of the tongue and oral cavity of a cat was studied. A chart of the afferent innervation of both mechanosensory surfaces of the tongue (dorsal and ventral surfaces) with fibers of the anterior medial and posterior branches of the lingual nerve was drawn up on the basis of the experimental material. Different ratios of the mechanoreceptor reactions were described.", "contents": "[Participation of the fibers of the lingual nerve in the transmission of mechanosensitive information from the tongue and oral cavity of the cat]. The role of the lingual nerve fibers in the transmission of mechanosensory information from the receptors of the tongue and oral cavity of a cat was studied. A chart of the afferent innervation of both mechanosensory surfaces of the tongue (dorsal and ventral surfaces) with fibers of the anterior medial and posterior branches of the lingual nerve was drawn up on the basis of the experimental material. Different ratios of the mechanoreceptor reactions were described."} {"id": "PMID:179641", "title": "[Plasma kinin system components of rabbits in acute inflammation].", "content": "During the peak of the acute aseptic inflammation of the subcutaneous connective tissue (on the 3rd-5th day) there occurred an activation of the plasma kinin system in the general circulation which expressed itself in an 1.5-2-fold increase in the activity of kallikreine, a 1.5-3-fold fall in the activity of kininase and in reduction by 25-26% of kininogen content. Thus, conditions were provided for the intesified formation and accumulation of free kinins participating in the second phase of permeability disorders of the vessels during the inflammation.", "contents": "[Plasma kinin system components of rabbits in acute inflammation]. During the peak of the acute aseptic inflammation of the subcutaneous connective tissue (on the 3rd-5th day) there occurred an activation of the plasma kinin system in the general circulation which expressed itself in an 1.5-2-fold increase in the activity of kallikreine, a 1.5-3-fold fall in the activity of kininase and in reduction by 25-26% of kininogen content. Thus, conditions were provided for the intesified formation and accumulation of free kinins participating in the second phase of permeability disorders of the vessels during the inflammation."} {"id": "PMID:179642", "title": "[Enzymatic activity in the osteoblasts of rabbits following combined trauma].", "content": "Experiments were conducted on young rabbits by the histochemical methods; the activity of NAD-, NADP-diaphorases, cytochromoxidase and alkaline phosphatase was studied in the osteoblasts 3, 6, 12, 24, 48 and 72 hours after combined radiation trauma. It appeared that a bone fracture led to an increase in the level of metabolic and energic processes in the osteoblasts as soon as in 12 hours. Irradiation of the animals depressed the activation (caused by the fracture) of all the enzymes investigated.", "contents": "[Enzymatic activity in the osteoblasts of rabbits following combined trauma]. Experiments were conducted on young rabbits by the histochemical methods; the activity of NAD-, NADP-diaphorases, cytochromoxidase and alkaline phosphatase was studied in the osteoblasts 3, 6, 12, 24, 48 and 72 hours after combined radiation trauma. It appeared that a bone fracture led to an increase in the level of metabolic and energic processes in the osteoblasts as soon as in 12 hours. Irradiation of the animals depressed the activation (caused by the fracture) of all the enzymes investigated."} {"id": "PMID:179643", "title": "[Cyclic 3',5'-adenosine monophosphate stimulation of chloramphenicol-acetyltransferase synthesis in bacterial cellular systems].", "content": "A study was made of the effect of cyclic cyclic 3',5'-adenosinmonophosphate (c-AMP) on the production of chloramphenicol-acetyltranspherase (CAT) enzyme by whole bacterial cells in the strains of E. coli CSH-2/R222 and WZ-78/R222 (cya855). It was shown that CAT synthesis in the E. coli WZ-78/R222 strain was two times less in comparison with the E. coli CSH-2/R222 strain. C-AMP only insignificantly increased the production of CAT by the E. coli CSH-2/R222 strain, but considerably influenced the production of this enzyme by the WZ-78/R222 strain.", "contents": "[Cyclic 3',5'-adenosine monophosphate stimulation of chloramphenicol-acetyltransferase synthesis in bacterial cellular systems]. A study was made of the effect of cyclic cyclic 3',5'-adenosinmonophosphate (c-AMP) on the production of chloramphenicol-acetyltranspherase (CAT) enzyme by whole bacterial cells in the strains of E. coli CSH-2/R222 and WZ-78/R222 (cya855). It was shown that CAT synthesis in the E. coli WZ-78/R222 strain was two times less in comparison with the E. coli CSH-2/R222 strain. C-AMP only insignificantly increased the production of CAT by the E. coli CSH-2/R222 strain, but considerably influenced the production of this enzyme by the WZ-78/R222 strain."} {"id": "PMID:179644", "title": "[Effect of morphine in vitro on the oxidative phosphorylation in rat liver mitochondria].", "content": "The rates of respiration in the presence of ADP and of phosphorylation as an ATP-ase activity of rat liver mitochondria was inhibited was in vitro by morphine with Ki=6.5 mM. The uncoupler-stimulated respiration of the mitochondria and the activity of ATP-ase and synthesis of ATP in the submitochondrial particles were not altered in the presence of morphine. It is suggested that morphine inhibited the adenine nucleotide transport through the mitochondrial membrane", "contents": "[Effect of morphine in vitro on the oxidative phosphorylation in rat liver mitochondria]. The rates of respiration in the presence of ADP and of phosphorylation as an ATP-ase activity of rat liver mitochondria was inhibited was in vitro by morphine with Ki=6.5 mM. The uncoupler-stimulated respiration of the mitochondria and the activity of ATP-ase and synthesis of ATP in the submitochondrial particles were not altered in the presence of morphine. It is suggested that morphine inhibited the adenine nucleotide transport through the mitochondrial membrane"} {"id": "PMID:179645", "title": "[Ubiquinone content in albino rat kidney mitochondria following unilateral nephrectomy].", "content": "Following unilateral nephrectomy (in 72 hours) the weight of the remaining kidney increased by 23%, and the activity of succinic dehydrogenase--by 43.2%. The concentration of oubichinon in the hypertrophied kidney and its mitochondria showed no significant change for 3 days after the nephrectomy.", "contents": "[Ubiquinone content in albino rat kidney mitochondria following unilateral nephrectomy]. Following unilateral nephrectomy (in 72 hours) the weight of the remaining kidney increased by 23%, and the activity of succinic dehydrogenase--by 43.2%. The concentration of oubichinon in the hypertrophied kidney and its mitochondria showed no significant change for 3 days after the nephrectomy."} {"id": "PMID:179646", "title": "[Morphological and biochemical study of the organs of immunogenesis during the growth of established glioblastoma multiforme in albino rat brain].", "content": "Morphological changes in the lympho-reticular organs (the thymus, lymph nodes, spleen) were studied and the content of the RNA was determined by the biochemical method in 92 rats during the growth of the glioblastoma multiforme (strain 101/12) in the brain. The reaction of the organs of immunogenesis depended on the stage of the disease. On the 6th day after the transplantation of the tumour the increased activity of the epithelial-reticular portion of the thymus, hyperplasia of the follicles in the lymph nodes, and increased produciton of the RNA was observed. As to the tumour-bearing animals the destruction of the lymphoid elements and decreased synthesis of the RNA was noted. A giradual cell depletion of the spleen was revealed morphologically.", "contents": "[Morphological and biochemical study of the organs of immunogenesis during the growth of established glioblastoma multiforme in albino rat brain]. Morphological changes in the lympho-reticular organs (the thymus, lymph nodes, spleen) were studied and the content of the RNA was determined by the biochemical method in 92 rats during the growth of the glioblastoma multiforme (strain 101/12) in the brain. The reaction of the organs of immunogenesis depended on the stage of the disease. On the 6th day after the transplantation of the tumour the increased activity of the epithelial-reticular portion of the thymus, hyperplasia of the follicles in the lymph nodes, and increased produciton of the RNA was observed. As to the tumour-bearing animals the destruction of the lymphoid elements and decreased synthesis of the RNA was noted. A giradual cell depletion of the spleen was revealed morphologically."} {"id": "PMID:179648", "title": "[Effect of qualitatively different carbohydrates on the lipoprotein spectrum and lipid composition of the blood in experimental animals].", "content": "Experiments on rats demonstrated that a high-carbohydrate diet with starch produced no changes in the lipoprotein composition and lipid concentration in the blood. Diets containing sucrose promoted an increase in triglycerides and of the pre-beta-lipoproteins. However, the effect of sucrose depended on the qualitative correlation of the carbohydrate and lipid components of the diet. A reduction of lipoproteins of low density and of the total cholesterol/phospholipid ratio on account of an increase of the latter in the blood was seen in rats given sucrose in the composition of the high-carbohydrate diet with a decreased amount of the saturated fat. Inclusion of sucrose into the diet with a physiological carbohydrate and lipid level (56 and 26% of total amount of calories, respectively) was accompanied by elevation of beta-lipoprotein level and an increase in the total cholesterol/phospholipid ratio.", "contents": "[Effect of qualitatively different carbohydrates on the lipoprotein spectrum and lipid composition of the blood in experimental animals]. Experiments on rats demonstrated that a high-carbohydrate diet with starch produced no changes in the lipoprotein composition and lipid concentration in the blood. Diets containing sucrose promoted an increase in triglycerides and of the pre-beta-lipoproteins. However, the effect of sucrose depended on the qualitative correlation of the carbohydrate and lipid components of the diet. A reduction of lipoproteins of low density and of the total cholesterol/phospholipid ratio on account of an increase of the latter in the blood was seen in rats given sucrose in the composition of the high-carbohydrate diet with a decreased amount of the saturated fat. Inclusion of sucrose into the diet with a physiological carbohydrate and lipid level (56 and 26% of total amount of calories, respectively) was accompanied by elevation of beta-lipoprotein level and an increase in the total cholesterol/phospholipid ratio."} {"id": "PMID:179649", "title": "[Role of bioenergetic changes in the mechanism of action of nonsteroid anti-inflammatory agents].", "content": "In experiments on rats the antiphlogistic action of sodium mephenaminate and salicylate was found to be more pronounced under conditions of ovalbumin than that of dextran inflammation. The antiphlogistic effect of sodium salicylate was greater than that of mephenaminate in ovalbumin inflammation; this correlated with a more marked drop in the content of lactic acid in the blood and with a more complete elimination of uncoupling of oxidative phosphorylation in the hepatic mitochondria than in case of mephenaminate injection. It is supposed that lowering the macroerg level by the principle of feed back action leads to intensification of phosphorylation; this provides elimination of inflammatory disturbances and can explain the antiphlogistic effect of the drugs.", "contents": "[Role of bioenergetic changes in the mechanism of action of nonsteroid anti-inflammatory agents]. In experiments on rats the antiphlogistic action of sodium mephenaminate and salicylate was found to be more pronounced under conditions of ovalbumin than that of dextran inflammation. The antiphlogistic effect of sodium salicylate was greater than that of mephenaminate in ovalbumin inflammation; this correlated with a more marked drop in the content of lactic acid in the blood and with a more complete elimination of uncoupling of oxidative phosphorylation in the hepatic mitochondria than in case of mephenaminate injection. It is supposed that lowering the macroerg level by the principle of feed back action leads to intensification of phosphorylation; this provides elimination of inflammatory disturbances and can explain the antiphlogistic effect of the drugs."} {"id": "PMID:179650", "title": "A cholinoceptor antiserum: its pharmacological properties.", "content": "1 Sera of rabbits immunized against a nocotinic receptor-rich fraction, obtained from the electric organ of Torpedo marmorata, were tested for their pharmacological activity on different in vitro preparations. 2 Sera containing antibodies against the nicotinic receptor blocked neuromuscular transmission in the phrenic-nerve hemidiaphragm preparation without affecting the muscle responses evoked by direct electrical stimulation. Complement inactivated sera were still active. Immune sera, incubated for 15 min with a receptor-rich fraction, lost their activity. 3 The immune sera antagonized the responses elicited by acetylcholine on the frog rectus abdominis. 4 The immune sera tested in vitro decreased the compound action potential evoked in the superior cervical ganglion of the rat by electrical stimulation of the preganglionic nerve. 5 The sera did not show any activity on muscarinic receptors of the guinea-pig ileum preparation. 6 It is concluded that in sera obtained from immunized rabbits a substance is present with curare-like action, and that this activity is probably due to the presence of antibodies against the nicotinic receptor.", "contents": "A cholinoceptor antiserum: its pharmacological properties. 1 Sera of rabbits immunized against a nocotinic receptor-rich fraction, obtained from the electric organ of Torpedo marmorata, were tested for their pharmacological activity on different in vitro preparations. 2 Sera containing antibodies against the nicotinic receptor blocked neuromuscular transmission in the phrenic-nerve hemidiaphragm preparation without affecting the muscle responses evoked by direct electrical stimulation. Complement inactivated sera were still active. Immune sera, incubated for 15 min with a receptor-rich fraction, lost their activity. 3 The immune sera antagonized the responses elicited by acetylcholine on the frog rectus abdominis. 4 The immune sera tested in vitro decreased the compound action potential evoked in the superior cervical ganglion of the rat by electrical stimulation of the preganglionic nerve. 5 The sera did not show any activity on muscarinic receptors of the guinea-pig ileum preparation. 6 It is concluded that in sera obtained from immunized rabbits a substance is present with curare-like action, and that this activity is probably due to the presence of antibodies against the nicotinic receptor."} {"id": "PMID:179651", "title": "The reasons people give for taking overdoses.", "content": "This study investigates the reasons people give for taking overdoses of drugs. A representative sample of 128 subjects were interviewed immediately after their recovery from an overdose. During the interview they were given alternative reasons for taking overdoses and asked to choose any that applied to them. Spontaneous comments about suicidal intent were also recorded. Of the subjects, 44% indicated that they had wanted to die. On the basis of their choices 33% were 'seeking help', 42% 'escaping from the situation', 52% 'obtaining relief from a terrible state of mind' and 19% 'trying to influence someone'. The association between these various reasons and other expected effects or feelings associated with the act were examined by means of multidimensional scaling analysis. In addition, the characteristics of those expressing suicidal intent and other reasons were studied, together with such consequences as toxic effects and psychiatric after-care. The possibility is discussed that a large proportion of those indicating suicidal intent do so either to gain social acceptability for their act or to influence helping agencies.", "contents": "The reasons people give for taking overdoses. This study investigates the reasons people give for taking overdoses of drugs. A representative sample of 128 subjects were interviewed immediately after their recovery from an overdose. During the interview they were given alternative reasons for taking overdoses and asked to choose any that applied to them. Spontaneous comments about suicidal intent were also recorded. Of the subjects, 44% indicated that they had wanted to die. On the basis of their choices 33% were 'seeking help', 42% 'escaping from the situation', 52% 'obtaining relief from a terrible state of mind' and 19% 'trying to influence someone'. The association between these various reasons and other expected effects or feelings associated with the act were examined by means of multidimensional scaling analysis. In addition, the characteristics of those expressing suicidal intent and other reasons were studied, together with such consequences as toxic effects and psychiatric after-care. The possibility is discussed that a large proportion of those indicating suicidal intent do so either to gain social acceptability for their act or to influence helping agencies."} {"id": "PMID:179652", "title": "Rectilinear scanning in the detection of acute myocardial infarction.", "content": "Myocardial scintigraphy with phosphate bone scanning agents is a new and very useful development in the detection of acute myocardial infarction. Initial experience using a rectilinear scanner is described in 50 consecutive patients admitted to hospital because of suspected myocardial infarction. The routine dose was 15 mCi/5 mg, 99Tcm stannous pyrophosphate intravenously with anterior, left anterior oblique, and lateral scans obtained 45-90 minutes after injection. There was only one false negative scan in 17 patients with proven acute myocardial infarction and that was 16 days after onset. There was no proven false positive investigation in seven patients in which fresh myocardial infarction could be definitely excluded, or in a further 11 cases in which it could be excluded with reasonable confidence. Myocardial scintigraphy was considered helpful in resolving the diagnostic problem in 27 out of 29 equivocal cases. It is concluded that myocardial scintigraphy with a rectilinear scanner is a highly accurate and safe procedure in the detection of acute myocardial infarction. The optimum scanning time is two to six days after onset of suspected infarction, when a diagnostic accuracy approaching 100 per cent can be expected.", "contents": "Rectilinear scanning in the detection of acute myocardial infarction. Myocardial scintigraphy with phosphate bone scanning agents is a new and very useful development in the detection of acute myocardial infarction. Initial experience using a rectilinear scanner is described in 50 consecutive patients admitted to hospital because of suspected myocardial infarction. The routine dose was 15 mCi/5 mg, 99Tcm stannous pyrophosphate intravenously with anterior, left anterior oblique, and lateral scans obtained 45-90 minutes after injection. There was only one false negative scan in 17 patients with proven acute myocardial infarction and that was 16 days after onset. There was no proven false positive investigation in seven patients in which fresh myocardial infarction could be definitely excluded, or in a further 11 cases in which it could be excluded with reasonable confidence. Myocardial scintigraphy was considered helpful in resolving the diagnostic problem in 27 out of 29 equivocal cases. It is concluded that myocardial scintigraphy with a rectilinear scanner is a highly accurate and safe procedure in the detection of acute myocardial infarction. The optimum scanning time is two to six days after onset of suspected infarction, when a diagnostic accuracy approaching 100 per cent can be expected."} {"id": "PMID:179654", "title": "Technetium-99m labelled imidodiphosphate: an improved bone-scanning radiopharmaceutical.", "content": "Technetium-99m labelled imidodiphosphate was prepared in the presence of stannous ions. It was evaluated as a bone-scanning agent in animals and patients. Comparative tissue distribution studies in mice showed a relatively higher uptake of radioactivity in bone when 99Tcm -labelled pyrophosphate and diphosphonate. Accumulation of radioactivity in soft tissues, especially kidneys, was less with this radiopharmaceutical. Results in patients were most satisfactory in delineating skeletal bone and identifying bone lesions with relatively small tracer doses of the radiopharmaceutical.", "contents": "Technetium-99m labelled imidodiphosphate: an improved bone-scanning radiopharmaceutical. Technetium-99m labelled imidodiphosphate was prepared in the presence of stannous ions. It was evaluated as a bone-scanning agent in animals and patients. Comparative tissue distribution studies in mice showed a relatively higher uptake of radioactivity in bone when 99Tcm -labelled pyrophosphate and diphosphonate. Accumulation of radioactivity in soft tissues, especially kidneys, was less with this radiopharmaceutical. Results in patients were most satisfactory in delineating skeletal bone and identifying bone lesions with relatively small tracer doses of the radiopharmaceutical."} {"id": "PMID:179657", "title": "Nitrazepam: lastingly effective but trouble on withdrawal.", "content": "The sleep of 10 volunteers with an average age of 57 years was recorded electrophysiologically before, during, and after nitrazepam 5 mg nightly for 10 weeks. Sleep was longer and less broken on the drug and no tolerance was obvious after two months' use. Withdrawal of the drug, however, caused sleep to be temporarily worse than before the drug had been taken. Slow-wave sleep was reduced by nitrazepam, but the accompanying secretion of growth hormone was not impaired.", "contents": "Nitrazepam: lastingly effective but trouble on withdrawal. The sleep of 10 volunteers with an average age of 57 years was recorded electrophysiologically before, during, and after nitrazepam 5 mg nightly for 10 weeks. Sleep was longer and less broken on the drug and no tolerance was obvious after two months' use. Withdrawal of the drug, however, caused sleep to be temporarily worse than before the drug had been taken. Slow-wave sleep was reduced by nitrazepam, but the accompanying secretion of growth hormone was not impaired."} {"id": "PMID:179659", "title": "Attitudes and advice after myocardial infarction.", "content": "While medical opinion increasingly favours an active approach to rehabilitation after myocardial infarction, interviews with 40 patients and their relatives showed a low degree of understanding of medical advice and information. There was general satisfaction with treatment, but communication was seen as often being inadequate, vague, and conflicting.", "contents": "Attitudes and advice after myocardial infarction. While medical opinion increasingly favours an active approach to rehabilitation after myocardial infarction, interviews with 40 patients and their relatives showed a low degree of understanding of medical advice and information. There was general satisfaction with treatment, but communication was seen as often being inadequate, vague, and conflicting."} {"id": "PMID:179661", "title": "Metabolic regulations of the rhythmic activity in pacemaker neurons. II. Metabolically induced conversions of beating to bursting pacemaker activity in isolated Aplysia neurons.", "content": "In pacemaker neurons of the sea hare Aplysia californica, isolated from their synaptic, ephaptic and humoral inputs, conversion of the regular beating to a bursting discharge pattern can be induced by certain cell metabolites. Administration of the phosphofructokinase (PFK) activator fructose-6-phosphate (F-6-P), or its nonmetabolizable analogue 1-deoxy-F-6-P, induced bursting discharges in R3, R5, R6 and R11 neurons, with spike doublets and triplets appearing transiently in the time pattern. With another PFK activitor, adenosine-5-monophosphate, only double spikes have been noted in R7, R8 and R14 neurons. Burst activity was induced also in the presence of the fructose-1,6-diphosphatase activators, citrate and 3-phosphoglycerate, in R9, R10 and R12 neurons. Cyclic 3',5'-AMP, which also activates the PFK (beside other effects on cellular metabolism), induced bursting discharges in all R3-R14 neurons. In contrast, the inhibitors of the PFK, citrate and ATP, decreased the spike activity of the bursting L3 and L6 neurons, even changing L3 neurons to the regular beating type. Among a variety of cell metabolites tested only pyruvate was able to induce a burst-like tendency in R9 neurons. The characteristic bursting patterns which appeared in the presence of the described metabolic effectors could not be duplicated by low Ca2+ and/or high K+ media nor by artificial shifts in membrane potential triggered by depolarizing and hyperpolarizing currents.", "contents": "Metabolic regulations of the rhythmic activity in pacemaker neurons. II. Metabolically induced conversions of beating to bursting pacemaker activity in isolated Aplysia neurons. In pacemaker neurons of the sea hare Aplysia californica, isolated from their synaptic, ephaptic and humoral inputs, conversion of the regular beating to a bursting discharge pattern can be induced by certain cell metabolites. Administration of the phosphofructokinase (PFK) activator fructose-6-phosphate (F-6-P), or its nonmetabolizable analogue 1-deoxy-F-6-P, induced bursting discharges in R3, R5, R6 and R11 neurons, with spike doublets and triplets appearing transiently in the time pattern. With another PFK activitor, adenosine-5-monophosphate, only double spikes have been noted in R7, R8 and R14 neurons. Burst activity was induced also in the presence of the fructose-1,6-diphosphatase activators, citrate and 3-phosphoglycerate, in R9, R10 and R12 neurons. Cyclic 3',5'-AMP, which also activates the PFK (beside other effects on cellular metabolism), induced bursting discharges in all R3-R14 neurons. In contrast, the inhibitors of the PFK, citrate and ATP, decreased the spike activity of the bursting L3 and L6 neurons, even changing L3 neurons to the regular beating type. Among a variety of cell metabolites tested only pyruvate was able to induce a burst-like tendency in R9 neurons. The characteristic bursting patterns which appeared in the presence of the described metabolic effectors could not be duplicated by low Ca2+ and/or high K+ media nor by artificial shifts in membrane potential triggered by depolarizing and hyperpolarizing currents."} {"id": "PMID:179662", "title": "Effects of respiratory gases on cytochrome A in intact cerebral cortex: is there a critical Po2?", "content": "Changes in the redox level of cytochrome a and in the amount of oxygenated hemoglobin were measured by dual wavelength reflectance spectrophotometry in the intact cerebral cortex of cats (cerveau isol\u00e9 preparation) and in unanesthetized rabbits with chronically implanted cranial windows. Increases in inspired oxygen were accompanied by an increase in the oxidation level of cytochrome a and an increase in the amount of oxygenated hemoglobin in the optical field. These changes were larger in the presence of 5% CO2. Reduction of the inspired oxygen concentration produced a decrease in the oxidation/reduction ratio of cytochrome a and a disoxygenation of hemoglobin. The presence of CO2 at these lower oxygen levels diminished the reduction of cytochrome a and the disoxygenation of hemoglobin. These data indicate that, in the resting subject, the reduction levels of cytochrome a are well above the low values seen in isolated mitochondria. They also indicate that the blood supply to the cerebral cortex is regulated at a level of slight hypoxia.", "contents": "Effects of respiratory gases on cytochrome A in intact cerebral cortex: is there a critical Po2? Changes in the redox level of cytochrome a and in the amount of oxygenated hemoglobin were measured by dual wavelength reflectance spectrophotometry in the intact cerebral cortex of cats (cerveau isol\u00e9 preparation) and in unanesthetized rabbits with chronically implanted cranial windows. Increases in inspired oxygen were accompanied by an increase in the oxidation level of cytochrome a and an increase in the amount of oxygenated hemoglobin in the optical field. These changes were larger in the presence of 5% CO2. Reduction of the inspired oxygen concentration produced a decrease in the oxidation/reduction ratio of cytochrome a and a disoxygenation of hemoglobin. The presence of CO2 at these lower oxygen levels diminished the reduction of cytochrome a and the disoxygenation of hemoglobin. These data indicate that, in the resting subject, the reduction levels of cytochrome a are well above the low values seen in isolated mitochondria. They also indicate that the blood supply to the cerebral cortex is regulated at a level of slight hypoxia."} {"id": "PMID:179663", "title": "[Y-maze learning in two strains of mice. Effects of instrumental and pharmacologic sleep deprivation].", "content": "Effects of instrumental and pharmacological deprivation of sleep on Y-maze learning have been studied in two inbred strains of mice (C57BR/cd/Orl and C57BL/6/Orl), having identical sleep rhythms, but mainly differing in their ability to learn. Administration of alpha-methyl-DOPA (100 mg/kg) provokes complete suppression of paradoxical sleep (PS) for 9-11 h. Injection immediately after each training session over the first 5 days caused a delay in acquisition of an active avoidance task in C57BR mice. Treated C57BL/6 mice exhibited a significant facilitation of acquisition. Similar results were obtained by instrumental deprivation of sleep for 10 h.", "contents": "[Y-maze learning in two strains of mice. Effects of instrumental and pharmacologic sleep deprivation]. Effects of instrumental and pharmacological deprivation of sleep on Y-maze learning have been studied in two inbred strains of mice (C57BR/cd/Orl and C57BL/6/Orl), having identical sleep rhythms, but mainly differing in their ability to learn. Administration of alpha-methyl-DOPA (100 mg/kg) provokes complete suppression of paradoxical sleep (PS) for 9-11 h. Injection immediately after each training session over the first 5 days caused a delay in acquisition of an active avoidance task in C57BR mice. Treated C57BL/6 mice exhibited a significant facilitation of acquisition. Similar results were obtained by instrumental deprivation of sleep for 10 h."} {"id": "PMID:179665", "title": "Frequency facilitation and post-tetanic potentiation of a unitary synaptic potential in Aplysia californica are limited by different processes.", "content": "Post-tetanic potentiation (PTP) of the monosynaptic and unitary excitatory postsynaptic potential (EPSP) recorded in cell R15 of the abdominal ganglion of Aplysia californica was observed after repetitive stimulation of the right visceropleural connective. PTP at this synapse developed after a few pulses (about 20) and after trains of low frequency stimulation (1/2 sec) under normal physiological conditions of media and temperature. No phase of post-tetanic depression was observed. Evidence is presented that the PTP is due to an increase in transmitter release. The amplitude of the PTP was a function of the frequency and number of stimuli in the preceding train. The PTP was observed to decay, with a single exponential time course, to the size of an isolated EPSP. The rate constant of PTP decay depended upon both the frequency and number of stimuli in the preceding train. The magnitude of the various types of synaptic plasticities seen at this junction, i.e., synaptic depression, frequency facilitation and PTP, correlated with the size of an isolated EPSP as well as with each other. Based on the analysis of the data in terms of a flow model of transmitter release, it is concluded that: (a) during a train of repetitive stimulation the net rate of transmitter supply into the immediately available pool (net transmitter mobilization) increases, the efficiency of the release mechanism (fractional release) increases, and the pool of immediately available transmitter depletes; (b) upon the cessation of the train, as the peak amplitude of PTP is approached, the increased but diminishing rate of net transmitter mobilization refills the available pool to its equilibrium size, while the fractional release is still elevated; (c) during the PTP period after the peak potentiation, the elevated fractional release slowly decays with a single exponential time course; (d) the size of the facilitated EPSPs during the train is limited by the net rate of transmitter supply, although the efficiency of release is also increased; while the size of the EPSPs during the falling phase of the PTP period is determined solely by an increased efficiency of the release mechanism; and (e) the rising phase of the PTP observed in the period shortly after termination of the train is produced by the refilling of the depleted pool of available transmitter in the presence of an elevated release efficiency.", "contents": "Frequency facilitation and post-tetanic potentiation of a unitary synaptic potential in Aplysia californica are limited by different processes. Post-tetanic potentiation (PTP) of the monosynaptic and unitary excitatory postsynaptic potential (EPSP) recorded in cell R15 of the abdominal ganglion of Aplysia californica was observed after repetitive stimulation of the right visceropleural connective. PTP at this synapse developed after a few pulses (about 20) and after trains of low frequency stimulation (1/2 sec) under normal physiological conditions of media and temperature. No phase of post-tetanic depression was observed. Evidence is presented that the PTP is due to an increase in transmitter release. The amplitude of the PTP was a function of the frequency and number of stimuli in the preceding train. The PTP was observed to decay, with a single exponential time course, to the size of an isolated EPSP. The rate constant of PTP decay depended upon both the frequency and number of stimuli in the preceding train. The magnitude of the various types of synaptic plasticities seen at this junction, i.e., synaptic depression, frequency facilitation and PTP, correlated with the size of an isolated EPSP as well as with each other. Based on the analysis of the data in terms of a flow model of transmitter release, it is concluded that: (a) during a train of repetitive stimulation the net rate of transmitter supply into the immediately available pool (net transmitter mobilization) increases, the efficiency of the release mechanism (fractional release) increases, and the pool of immediately available transmitter depletes; (b) upon the cessation of the train, as the peak amplitude of PTP is approached, the increased but diminishing rate of net transmitter mobilization refills the available pool to its equilibrium size, while the fractional release is still elevated; (c) during the PTP period after the peak potentiation, the elevated fractional release slowly decays with a single exponential time course; (d) the size of the facilitated EPSPs during the train is limited by the net rate of transmitter supply, although the efficiency of release is also increased; while the size of the EPSPs during the falling phase of the PTP period is determined solely by an increased efficiency of the release mechanism; and (e) the rising phase of the PTP observed in the period shortly after termination of the train is produced by the refilling of the depleted pool of available transmitter in the presence of an elevated release efficiency."} {"id": "PMID:179667", "title": "Dopamine, serotonin and related compounds: presynaptic effects on synaptic depression, frequency facilitation, and post-tetanic potentiation at a synapse in Aplysia californica.", "content": "Dopamine, serotonin and related compounds (referred to collectively as biogenic amines) were found to modify transmission at the presumably cholinergic synapse made by an axon in the right visceropleural connective onto cell R15 of the abdominal ganglion of Aplysia californica. (1) With chronic application, dopamine hyperpolarizes R15, and serotonin depolarizes R15. Both actions upon the membrane potential desensitize in 10 min. All the actions described below were studied with chronic perfusion of the biogenic amines after desensitization of this postsynaptic action. (2) The biogenic amines drastically reduce the size of the EPSP evoked at the synapse under investigation; but they do not alter the ACh potential evoked in the soma of R15. (3) The biogenic amines reduce the amplitude of synaptic depression. The relationship between the effects of the amines on the size of an isolated EPSP and on synaptic depression differed from this relationship as affected by post-tetanic potentiation (PTP) or by changes in the Ca2+-Mg2+ balance. (4) The biogenic amines increase frequency facilitation, when the latter is defined as the ratio of the facilitated to the isolated EPSP. However, the absolute magnitude of the facilitated EPSP is always reduced at long times after introduction of the agent; shortly after introduction of the biogenic amines the absolute magnitude of the facilitated EPSP is unaffected in most preparations.", "contents": "Dopamine, serotonin and related compounds: presynaptic effects on synaptic depression, frequency facilitation, and post-tetanic potentiation at a synapse in Aplysia californica. Dopamine, serotonin and related compounds (referred to collectively as biogenic amines) were found to modify transmission at the presumably cholinergic synapse made by an axon in the right visceropleural connective onto cell R15 of the abdominal ganglion of Aplysia californica. (1) With chronic application, dopamine hyperpolarizes R15, and serotonin depolarizes R15. Both actions upon the membrane potential desensitize in 10 min. All the actions described below were studied with chronic perfusion of the biogenic amines after desensitization of this postsynaptic action. (2) The biogenic amines drastically reduce the size of the EPSP evoked at the synapse under investigation; but they do not alter the ACh potential evoked in the soma of R15. (3) The biogenic amines reduce the amplitude of synaptic depression. The relationship between the effects of the amines on the size of an isolated EPSP and on synaptic depression differed from this relationship as affected by post-tetanic potentiation (PTP) or by changes in the Ca2+-Mg2+ balance. (4) The biogenic amines increase frequency facilitation, when the latter is defined as the ratio of the facilitated to the isolated EPSP. However, the absolute magnitude of the facilitated EPSP is always reduced at long times after introduction of the agent; shortly after introduction of the biogenic amines the absolute magnitude of the facilitated EPSP is unaffected in most preparations."} {"id": "PMID:179668", "title": "Heterosynaptic inhibition modifies the presynaptic plasticities of the transmission process at the synapse in Aplysia californica.", "content": "The monosynaptic and unitary excitatory postsynpatic potential (EPSP) observed in cell R15 of the abdominal ganglion of Aplysia californica upon minimal stimulation of the right visceropleural connective exhibits several presynaptic plasticities (synaptic depression, frequency facilitation, post-tetanic potentiation). We studiied effects of branchial nerve stimulation (heterosynaptic stimulation) on these plasticities of the homosynaptic (right connective) path. A burst of heterosynaptic stimulation (20 pulses at 4/sec) decreased the amplitude of an isolated homosynaptic EPSP. The rate of recovery from heterosynaptic inhibition (HSI) was a function of the rate of stimulation of the homosynaptic path so that at a stimulus frequency of 1 pulse/sec to the right connective (RC) the HSI lasted less than 20 sec while at a RC stimulus frequency of 1/10 sec the HSI persisted for more than 60 sec. While the frequency facilitated EPSP (during homosynaptic stimulation at 1/sec) was only transiently affected by heterosynaptic stimulation the effect on the subsequent post-tetanic potentiation was much more pronounced and longer lasting (more than 30 min). This suggests a specific effect of HSI on the rate constant of decay of elevated fractional release, as observed upon bath applications of biogenic amines. Heterosynaptic stimulation also reduces synaptic depression but the reduction in the depression is more than would be caused by comparable reduction of the first EPSP of a pair of high Mg2+, low Ca2+ or the addition of carbachol to the perfusion medium. The duration of the effect on synaptic depression was the same as the effect on EPSP1.", "contents": "Heterosynaptic inhibition modifies the presynaptic plasticities of the transmission process at the synapse in Aplysia californica. The monosynaptic and unitary excitatory postsynpatic potential (EPSP) observed in cell R15 of the abdominal ganglion of Aplysia californica upon minimal stimulation of the right visceropleural connective exhibits several presynaptic plasticities (synaptic depression, frequency facilitation, post-tetanic potentiation). We studiied effects of branchial nerve stimulation (heterosynaptic stimulation) on these plasticities of the homosynaptic (right connective) path. A burst of heterosynaptic stimulation (20 pulses at 4/sec) decreased the amplitude of an isolated homosynaptic EPSP. The rate of recovery from heterosynaptic inhibition (HSI) was a function of the rate of stimulation of the homosynaptic path so that at a stimulus frequency of 1 pulse/sec to the right connective (RC) the HSI lasted less than 20 sec while at a RC stimulus frequency of 1/10 sec the HSI persisted for more than 60 sec. While the frequency facilitated EPSP (during homosynaptic stimulation at 1/sec) was only transiently affected by heterosynaptic stimulation the effect on the subsequent post-tetanic potentiation was much more pronounced and longer lasting (more than 30 min). This suggests a specific effect of HSI on the rate constant of decay of elevated fractional release, as observed upon bath applications of biogenic amines. Heterosynaptic stimulation also reduces synaptic depression but the reduction in the depression is more than would be caused by comparable reduction of the first EPSP of a pair of high Mg2+, low Ca2+ or the addition of carbachol to the perfusion medium. The duration of the effect on synaptic depression was the same as the effect on EPSP1."} {"id": "PMID:179672", "title": "Failure of procaine penicillin and zinc bacitracin to modify the response of the fowl to stressors.", "content": "1. The effect of either procaine penicillin or zinc bacitracin (25 mg active base/kg food) on the response of young birds to three different stressors - withdrawal of food for 18 h, exposure to cold for 24 h or treatment with ACTH- has been examined. 2. Neither antibiotic had any consistent effect on the stress responses. 3. It is concluded that neither penicillin nor bacitracin has any stress-ameliorating activity at least under the conditions of the test.", "contents": "Failure of procaine penicillin and zinc bacitracin to modify the response of the fowl to stressors. 1. The effect of either procaine penicillin or zinc bacitracin (25 mg active base/kg food) on the response of young birds to three different stressors - withdrawal of food for 18 h, exposure to cold for 24 h or treatment with ACTH- has been examined. 2. Neither antibiotic had any consistent effect on the stress responses. 3. It is concluded that neither penicillin nor bacitracin has any stress-ameliorating activity at least under the conditions of the test."} {"id": "PMID:179674", "title": "[Subcellular distribution of the protein kinase activity in the normal and neoplastic thyroid tissue of the rat].", "content": "Thyroid tissue has been fractionnated by centrifugation (105 000 q) of its homogenate. Protein-kinase activity in presence of histone is distributed in nuclei (11.5%) mitochondira (22.8%), microsomes (9.8%) and soluble fraction (56%); it is activated by cyclic AMP and GMP, mostly in soluble and nuclear fractions. Protein-kinase activity of total homogenate of neoplasic thyroid (strain 1-5G Wollman) in presence of histone is 3 times higher than in normal tissue and more activated by cAMP. In absence of histone, protein-kinase activity is the more important in mitochondrial and microsomal fractions of normal thyroid and in soluble and nuclear fraction of neoplastic tissue.", "contents": "[Subcellular distribution of the protein kinase activity in the normal and neoplastic thyroid tissue of the rat]. Thyroid tissue has been fractionnated by centrifugation (105 000 q) of its homogenate. Protein-kinase activity in presence of histone is distributed in nuclei (11.5%) mitochondira (22.8%), microsomes (9.8%) and soluble fraction (56%); it is activated by cyclic AMP and GMP, mostly in soluble and nuclear fractions. Protein-kinase activity of total homogenate of neoplasic thyroid (strain 1-5G Wollman) in presence of histone is 3 times higher than in normal tissue and more activated by cAMP. In absence of histone, protein-kinase activity is the more important in mitochondrial and microsomal fractions of normal thyroid and in soluble and nuclear fraction of neoplastic tissue."} {"id": "PMID:179675", "title": "[Presence of various protein kinases and of partially copurified endogenous substrates in the soluble fraction of an experimental tumor of the rat thyroid gland].", "content": "Various fractions containing protein-kinases have been partly purified from supernatant (105 000 g) of an experimental rat's thyroid cancer (1-8 Wollman). These fractions are activated at different levels by cyclic nucleotides and present an unequal affinity for protamine; they phosphorylate an endogenous substrate apparently copurified with the enzyme fractions and adorbed with them on calcium phosphate gel.", "contents": "[Presence of various protein kinases and of partially copurified endogenous substrates in the soluble fraction of an experimental tumor of the rat thyroid gland]. Various fractions containing protein-kinases have been partly purified from supernatant (105 000 g) of an experimental rat's thyroid cancer (1-8 Wollman). These fractions are activated at different levels by cyclic nucleotides and present an unequal affinity for protamine; they phosphorylate an endogenous substrate apparently copurified with the enzyme fractions and adorbed with them on calcium phosphate gel."} {"id": "PMID:179676", "title": "[Effects of chloramphenicol and thiamphenicol on sleep of the mouse].", "content": "The oral administration of 0.25-2.0 g/kg of chloramphenicol at 9h selectively suppresses paradoxical sleep in mice for a duration of 2-4 hours. A dose of 1 g/kg given at 17h suppresses paradoxical sleep for 7 hours. Slow wave sleep decreased for 2 hours after administration. Thiamphenicol (1 g/kg) has no effect under the same conditions.", "contents": "[Effects of chloramphenicol and thiamphenicol on sleep of the mouse]. The oral administration of 0.25-2.0 g/kg of chloramphenicol at 9h selectively suppresses paradoxical sleep in mice for a duration of 2-4 hours. A dose of 1 g/kg given at 17h suppresses paradoxical sleep for 7 hours. Slow wave sleep decreased for 2 hours after administration. Thiamphenicol (1 g/kg) has no effect under the same conditions."} {"id": "PMID:179677", "title": "[Secretions of GH, FSH and LH during sleep of the normal child and the child with retarded growth].", "content": "In normal children the major GH release begins during NREM sleep of first cycle. At puberty secretion of gonadotropins is enhanced and secretion of LH occurs with the same periodicity as the sleep cycles. Two groups of dwarfish are seen: the first lacks both GH secretion during sleep and the increase of gonadotropins at puberty. The second group exhibits GH, LH and FSH secretion patterns similar to normal children. Study of secretion patterns of GH, FSH and LH during sleep in children can document the degree of maturation of the hypothalamic pituitary hormonal system.", "contents": "[Secretions of GH, FSH and LH during sleep of the normal child and the child with retarded growth]. In normal children the major GH release begins during NREM sleep of first cycle. At puberty secretion of gonadotropins is enhanced and secretion of LH occurs with the same periodicity as the sleep cycles. Two groups of dwarfish are seen: the first lacks both GH secretion during sleep and the increase of gonadotropins at puberty. The second group exhibits GH, LH and FSH secretion patterns similar to normal children. Study of secretion patterns of GH, FSH and LH during sleep in children can document the degree of maturation of the hypothalamic pituitary hormonal system."} {"id": "PMID:179678", "title": "Stimulation of calcium accumulation in cardiac sarcolemma by protein kinase.", "content": "Sarcolemmal membranes isolated from guinea pig heart ventricles contained an ATP-dependent calcium-sequestering activity. Sarcolemmal calcium accumulation but not binding was enhanced by preincubation of membranes with exogenous protein kinase, with cyclic AMP, or with isoproterenol. Protein kinase (EC 2.7.1.37) increased the V of Ca2+ accumulation by sarcolemma without any significant effect on the affinity for Ca2+. The endogenous protein kinase activity present in isolated sarcolemma affected membrane phosphorylation. Cyclic AMP increased the endogenous kinase activity modestly, whereas histone increased it significantly. Exogenous protein kinase also catalyzed phosphorylation of these membranes. Endogenous and exogenous kinase-catalyzed phosphorylation of sarcolemma was hydroxylamine-insensitive. Ca2+-dependent ATPase (EC 3.6.1.3) (extra ATPase) activity of sarcolemma was also increased by protein kinase.", "contents": "Stimulation of calcium accumulation in cardiac sarcolemma by protein kinase. Sarcolemmal membranes isolated from guinea pig heart ventricles contained an ATP-dependent calcium-sequestering activity. Sarcolemmal calcium accumulation but not binding was enhanced by preincubation of membranes with exogenous protein kinase, with cyclic AMP, or with isoproterenol. Protein kinase (EC 2.7.1.37) increased the V of Ca2+ accumulation by sarcolemma without any significant effect on the affinity for Ca2+. The endogenous protein kinase activity present in isolated sarcolemma affected membrane phosphorylation. Cyclic AMP increased the endogenous kinase activity modestly, whereas histone increased it significantly. Exogenous protein kinase also catalyzed phosphorylation of these membranes. Endogenous and exogenous kinase-catalyzed phosphorylation of sarcolemma was hydroxylamine-insensitive. Ca2+-dependent ATPase (EC 3.6.1.3) (extra ATPase) activity of sarcolemma was also increased by protein kinase."} {"id": "PMID:179679", "title": "The interaction of ligands with chemically modified phosphorylase b.", "content": "Phosphorylase b which had been inactivated with 5-diazo1H-tetrazole was specifically labelled with 4-iodoacetamidosalicylic acid (a fluorescent probe) or with N-(1-oxyl-2,2,6,6,-tetramethyl-4-piperidinyl)iodoacetamide (a spin label probe) so that the binding of ligands and accompanying conformational changes could be determined by fluorescence or electron spin resonance changes, respectively. The allosteric effector, AMP, causes conformational changes similar to those caused in the native enzyme. The affinity of binding of phosphate or AMP to the inhibited protein is the same as for the unmodified protein. The heterotropic interactions between glucose-1-phosphate or glycogen and AMP are much less in the inactivated enzyme than in unmodified phosphorylase. Using a light scattering assay, it is shown that the modified enzyme binds to glycogen less strongly than the native protein. Phosphorylase b which had been inactivated by carbodimide in the presence of glycine ethyl ester, resulting in the modification of one or more carboxyl groups, was labelled with the spin label probe described above. The modified enzyme has an affinity for AMP similar to that of the native enzyme. AMP binding to the modified enzyme is tightened by glycogen, weakened by glucose-6-phosphate and is unaffected by glucose-1-phosphate. The actions of 5-diazo-1H-tetrazole and carbodimide on phosphorylase are discussed in the light of the above observation.", "contents": "The interaction of ligands with chemically modified phosphorylase b. Phosphorylase b which had been inactivated with 5-diazo1H-tetrazole was specifically labelled with 4-iodoacetamidosalicylic acid (a fluorescent probe) or with N-(1-oxyl-2,2,6,6,-tetramethyl-4-piperidinyl)iodoacetamide (a spin label probe) so that the binding of ligands and accompanying conformational changes could be determined by fluorescence or electron spin resonance changes, respectively. The allosteric effector, AMP, causes conformational changes similar to those caused in the native enzyme. The affinity of binding of phosphate or AMP to the inhibited protein is the same as for the unmodified protein. The heterotropic interactions between glucose-1-phosphate or glycogen and AMP are much less in the inactivated enzyme than in unmodified phosphorylase. Using a light scattering assay, it is shown that the modified enzyme binds to glycogen less strongly than the native protein. Phosphorylase b which had been inactivated by carbodimide in the presence of glycine ethyl ester, resulting in the modification of one or more carboxyl groups, was labelled with the spin label probe described above. The modified enzyme has an affinity for AMP similar to that of the native enzyme. AMP binding to the modified enzyme is tightened by glycogen, weakened by glucose-6-phosphate and is unaffected by glucose-1-phosphate. The actions of 5-diazo-1H-tetrazole and carbodimide on phosphorylase are discussed in the light of the above observation."} {"id": "PMID:179680", "title": "Synthesis of biologically active spin-labelled radioactive cytidine diphosphodiglyceride, a novel probe for biological membranes.", "content": "A versatile synthesis of spin-labelled radioactive cytidine diphospho-sn-1,2-diacylglycerol (CDP-diglyceride) has been developed based on the combination of the enzymatic acylation of radioactive sn-glycero-3-phosphate with 12-doxyl stearic acid and the chemical conversion of the thus obtained spin-labelled radioactive phosphatidic acid with cytidine monophosphomorpholi-date into spin-labelled radioactive CDP-diglyceride. The method for the isolation and purification of the latter compound was described. This obtained CDP-[2-3H]diglyceride contained 10% of fatty acids of paramagnetic nature, presumably present as a covalently bound 12-doxyl stearic acid esters. The biological activity was tested by using the synthesized compound as a substrate in the mitochondrial biosynthesis of phosphatidylglycerol. It was found that spin-labelled CDP-[2-3H]diglyceride prepared as described can be converted in the presence of sn-[2-14C]-glycero-3-phosphate into a spin-labelled [2-3H, 2'-14C]phosphatidylglycerol with isolated rat liver mitochondria, establishing therefore that the site of its utilization is identical with the site of phosphatidylglycerol synthesis in isolated mitochondria, i.e. inner mitochondrial membrane. Results described demonstrate that the synthesized spin-labelled CDP-diglyceride can be used as a specific probe for the spin- and radioactive covalent labelling of polyglycerophosphatides of mitochondrial membranes. Some implications and further possibilities in the study of biological membranes using the spin-labelled radioactive CDP-diglyceride are discussed.", "contents": "Synthesis of biologically active spin-labelled radioactive cytidine diphosphodiglyceride, a novel probe for biological membranes. A versatile synthesis of spin-labelled radioactive cytidine diphospho-sn-1,2-diacylglycerol (CDP-diglyceride) has been developed based on the combination of the enzymatic acylation of radioactive sn-glycero-3-phosphate with 12-doxyl stearic acid and the chemical conversion of the thus obtained spin-labelled radioactive phosphatidic acid with cytidine monophosphomorpholi-date into spin-labelled radioactive CDP-diglyceride. The method for the isolation and purification of the latter compound was described. This obtained CDP-[2-3H]diglyceride contained 10% of fatty acids of paramagnetic nature, presumably present as a covalently bound 12-doxyl stearic acid esters. The biological activity was tested by using the synthesized compound as a substrate in the mitochondrial biosynthesis of phosphatidylglycerol. It was found that spin-labelled CDP-[2-3H]diglyceride prepared as described can be converted in the presence of sn-[2-14C]-glycero-3-phosphate into a spin-labelled [2-3H, 2'-14C]phosphatidylglycerol with isolated rat liver mitochondria, establishing therefore that the site of its utilization is identical with the site of phosphatidylglycerol synthesis in isolated mitochondria, i.e. inner mitochondrial membrane. Results described demonstrate that the synthesized spin-labelled CDP-diglyceride can be used as a specific probe for the spin- and radioactive covalent labelling of polyglycerophosphatides of mitochondrial membranes. Some implications and further possibilities in the study of biological membranes using the spin-labelled radioactive CDP-diglyceride are discussed."} {"id": "PMID:179681", "title": "Inhibition by saccharin of glucose-6-phosphatase: effects of alloxan in vivo and deoxycholate in vitro.", "content": "Inhibition by saccharin of rat liver glucose-6-phosphatase (EC 3.1.3.9) generally decreased as the pH increased in the range pH 4-8. This pattern was exhibited by homogenates from control and alloxan-treated animals assayed each in the absence and presence of 0.2% (w/v) deoxycholate. Saccharin inhibited in competitive fashion with respect to glucose-6-phosphate (glucose-6-P). There was a small increase in Km (glucose-6-P) but not K1 (saccharin) values in alloxan-treated rats when assays were conducted in the absence of deoxycholate. In the presence of this detergent there was no significant difference in these kinetic parameters between the alloxan-treated and control groups. Deoxycholate decreased Km (glucose-6-P) and increased K1 (saccharin) values. Calculations using these kinetic parameters indicate that, under usual hepatic glucose-6-P concentrations and relatively high levels of saccharin in liver, the inhibition by saccharin of glucose-6-phosphatase is unlikely to be of major significance in vivo.", "contents": "Inhibition by saccharin of glucose-6-phosphatase: effects of alloxan in vivo and deoxycholate in vitro. Inhibition by saccharin of rat liver glucose-6-phosphatase (EC 3.1.3.9) generally decreased as the pH increased in the range pH 4-8. This pattern was exhibited by homogenates from control and alloxan-treated animals assayed each in the absence and presence of 0.2% (w/v) deoxycholate. Saccharin inhibited in competitive fashion with respect to glucose-6-phosphate (glucose-6-P). There was a small increase in Km (glucose-6-P) but not K1 (saccharin) values in alloxan-treated rats when assays were conducted in the absence of deoxycholate. In the presence of this detergent there was no significant difference in these kinetic parameters between the alloxan-treated and control groups. Deoxycholate decreased Km (glucose-6-P) and increased K1 (saccharin) values. Calculations using these kinetic parameters indicate that, under usual hepatic glucose-6-P concentrations and relatively high levels of saccharin in liver, the inhibition by saccharin of glucose-6-phosphatase is unlikely to be of major significance in vivo."} {"id": "PMID:179682", "title": "Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity.", "content": "In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3',5'-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (pge2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents.", "contents": "Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity. In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3',5'-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (pge2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents."} {"id": "PMID:179683", "title": "Loss of ACTH biological activity in plasma during extraction with a commercial radioimmunoassay kit.", "content": "The process used for extracting adrenocorticotropic hormone (ACTH) from plasma in the Searle ACTH immunoassay kit involves a loss of 70-100% of the biological activity of the ACTH.", "contents": "Loss of ACTH biological activity in plasma during extraction with a commercial radioimmunoassay kit. The process used for extracting adrenocorticotropic hormone (ACTH) from plasma in the Searle ACTH immunoassay kit involves a loss of 70-100% of the biological activity of the ACTH."} {"id": "PMID:179684", "title": "Is cyclic guanosine monophosphate the internal 'second messenger' for cholinergic actions on central neurons?", "content": "The most consistent effects produced by intracellular injections of guanosine 3',5'-cyclic monophosphate (cGMP) (but not 5'-guanosine 5'-monophosphate in spinal motoneurons of cats are a rise in membrane conductance, acceleration in time course of spike potentials, and accentuation of the post-spike hyperpolarization. Associated changes in resting potential are smaller, less constant, and more often in the depolarizing than hyperpolarizing direction, cGMP tends to increase electrical excitability but reduces excitatory post-synaptic potential amplitudes. Most of the effects of intracellular cGMP are quite different from, or indeed opposite to, those of either extra- or intracellular applications of acetylcholine and therefore not consistent with the proposal that cGMP is the internal mediator of muscarinic actions.", "contents": "Is cyclic guanosine monophosphate the internal 'second messenger' for cholinergic actions on central neurons? The most consistent effects produced by intracellular injections of guanosine 3',5'-cyclic monophosphate (cGMP) (but not 5'-guanosine 5'-monophosphate in spinal motoneurons of cats are a rise in membrane conductance, acceleration in time course of spike potentials, and accentuation of the post-spike hyperpolarization. Associated changes in resting potential are smaller, less constant, and more often in the depolarizing than hyperpolarizing direction, cGMP tends to increase electrical excitability but reduces excitatory post-synaptic potential amplitudes. Most of the effects of intracellular cGMP are quite different from, or indeed opposite to, those of either extra- or intracellular applications of acetylcholine and therefore not consistent with the proposal that cGMP is the internal mediator of muscarinic actions."} {"id": "PMID:179685", "title": "Temperate phages of Clostridium perfringens type C1.", "content": "Four phages isolated from carrier strains of Clostridium perfringens type C belong to two classes. The three phages of class I, c1, c3, and c4, and homoimmune and serologically closely related. The phage of class II, c5, is heteroimmune to the class I phages and not related to them serologically. Transduction experiments with several of the phages were negative. Mutants of the indicator strain with surface alterations occurred spontaneously in stock cultures. Electron micrographs show the phages of each class to be distinct yet similar, having polyhedral heads of about the same diameter 55 nm, and long, flexible tails without sheaths or collars. Phages c4 and c5 were characterized for their lysogenic properties. Phage c4 was inducible with mitomycin C. Both c4 and c5 were temperate viruses by the test of stability of their respective lysogens to phage-specific antisera.", "contents": "Temperate phages of Clostridium perfringens type C1. Four phages isolated from carrier strains of Clostridium perfringens type C belong to two classes. The three phages of class I, c1, c3, and c4, and homoimmune and serologically closely related. The phage of class II, c5, is heteroimmune to the class I phages and not related to them serologically. Transduction experiments with several of the phages were negative. Mutants of the indicator strain with surface alterations occurred spontaneously in stock cultures. Electron micrographs show the phages of each class to be distinct yet similar, having polyhedral heads of about the same diameter 55 nm, and long, flexible tails without sheaths or collars. Phages c4 and c5 were characterized for their lysogenic properties. Phage c4 was inducible with mitomycin C. Both c4 and c5 were temperate viruses by the test of stability of their respective lysogens to phage-specific antisera."} {"id": "PMID:179686", "title": "Enumeration of sublethally heated staphylococci in some dried foods.", "content": "The effect of 45 substances to restore the salt tolerance of sublethally heat-injured Staphylococcus aureus was tested. Sodium pyruvate, yeast extract, L-histine, casitone (Difco), adenosine triphosphate, and acetylphosphate were effective. For enumeration a repair medium was first used, containing sodium pyruvate and penicillin in 1% skim milk. This step was followed by counting on Baird-Parker agar with penicillinase. This method was selective; fewer than 100 staphylococci/g food could be enumerated and it gave counts about 8 times higher than the method of Giolitti and Cantoni used as a five-tube most probable number technique. Heat injury sensitized S. aureus to polymyxin.", "contents": "Enumeration of sublethally heated staphylococci in some dried foods. The effect of 45 substances to restore the salt tolerance of sublethally heat-injured Staphylococcus aureus was tested. Sodium pyruvate, yeast extract, L-histine, casitone (Difco), adenosine triphosphate, and acetylphosphate were effective. For enumeration a repair medium was first used, containing sodium pyruvate and penicillin in 1% skim milk. This step was followed by counting on Baird-Parker agar with penicillinase. This method was selective; fewer than 100 staphylococci/g food could be enumerated and it gave counts about 8 times higher than the method of Giolitti and Cantoni used as a five-tube most probable number technique. Heat injury sensitized S. aureus to polymyxin."} {"id": "PMID:179687", "title": "Further studies on the relative antiviral efficacies of interferons induced by poly I:C and Mengo virus.", "content": "Mouse serum interferons induced by polyI:C, vesicular stomatitis virus (VSV), reovirus, and Mengo virus were assayed in monolayers of mouse L-929 cells by the plaque-reduction method using both VSV and Mengo as challenge viruses. Titers obtained with Mengo virus as challenge were all lower than with VSV. With the interferons induced by VSV, reovirus, and ployI:C, the reductions were of the order of two- to three-fold. With Mengo virus-induced interferon the reduction was much greater (about 17-fold). This offers an explanation for the observation that, unit for unit (measured by the plaque reduction of VSV), Mengo virus-induced interferon is only about 1/10 as effective as polyI:C-induced interferon in protecting mice against lethal infection with Mengo virus. The data are consistent with the hypothesis that an interferon antagonist is produced in the serum of mice infected with Mengo virus. This antagonist, which is not produced in mice inoculated with polyI:C, or reovirus, effectively blocks the antiviral action of interferon during Mengo virus infections, both in vivo and in vitro.", "contents": "Further studies on the relative antiviral efficacies of interferons induced by poly I:C and Mengo virus. Mouse serum interferons induced by polyI:C, vesicular stomatitis virus (VSV), reovirus, and Mengo virus were assayed in monolayers of mouse L-929 cells by the plaque-reduction method using both VSV and Mengo as challenge viruses. Titers obtained with Mengo virus as challenge were all lower than with VSV. With the interferons induced by VSV, reovirus, and ployI:C, the reductions were of the order of two- to three-fold. With Mengo virus-induced interferon the reduction was much greater (about 17-fold). This offers an explanation for the observation that, unit for unit (measured by the plaque reduction of VSV), Mengo virus-induced interferon is only about 1/10 as effective as polyI:C-induced interferon in protecting mice against lethal infection with Mengo virus. The data are consistent with the hypothesis that an interferon antagonist is produced in the serum of mice infected with Mengo virus. This antagonist, which is not produced in mice inoculated with polyI:C, or reovirus, effectively blocks the antiviral action of interferon during Mengo virus infections, both in vivo and in vitro."} {"id": "PMID:179688", "title": "Mannitol production in fungi during glucose catabolism.", "content": "The levels of phosphofructokinase (EC 2.7.1.11) and mannitol-1-phosphate dehydrogenase (EC 1.1.1.17) have been determined in a number of Mucor and Penicillium species. Mannitol-1-phosphate dehydrogenase was found in only one species of mucor, Mucor rouxii, and this with a specific activity much lower than that found in Penicillium species. All of the fungi tested in the Ascomycetes class exhibited mannitol-1-phosphate dehydrogenase activity. Interference from both mannitol-1-phosphate dehydrogenase and NADH oxidase (EC 1.6.99.5) caused some difficulty initially in detecting phosphofructokinase in Penicillium species; the Penicillium phosphofructokinase is very unstable. Penicillium notatum accumulates mannitol intracellularly; detection of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase (EC 3.1.3.22) activity in cell-free extracts indicates that the mannitol is formed from glucose via fructose-6-phosphate and mannitol-1-phosphate; no direct reduction of fructose to mannitol could be detected. The mannitol-1-phosphate dehydrogenase was specific for mannitol-1-phosphate and fructose-6-phosphate; NADP+(H) could not replace NAD+(H). The phosphatase (EC3.1.3.22) exhibited a distinct preference for mannitol-1-phosphate as substrate; all other substrates tested exhibited less than 25% of the activity observed with mannitol-1-phosphate.", "contents": "Mannitol production in fungi during glucose catabolism. The levels of phosphofructokinase (EC 2.7.1.11) and mannitol-1-phosphate dehydrogenase (EC 1.1.1.17) have been determined in a number of Mucor and Penicillium species. Mannitol-1-phosphate dehydrogenase was found in only one species of mucor, Mucor rouxii, and this with a specific activity much lower than that found in Penicillium species. All of the fungi tested in the Ascomycetes class exhibited mannitol-1-phosphate dehydrogenase activity. Interference from both mannitol-1-phosphate dehydrogenase and NADH oxidase (EC 1.6.99.5) caused some difficulty initially in detecting phosphofructokinase in Penicillium species; the Penicillium phosphofructokinase is very unstable. Penicillium notatum accumulates mannitol intracellularly; detection of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase (EC 3.1.3.22) activity in cell-free extracts indicates that the mannitol is formed from glucose via fructose-6-phosphate and mannitol-1-phosphate; no direct reduction of fructose to mannitol could be detected. The mannitol-1-phosphate dehydrogenase was specific for mannitol-1-phosphate and fructose-6-phosphate; NADP+(H) could not replace NAD+(H). The phosphatase (EC3.1.3.22) exhibited a distinct preference for mannitol-1-phosphate as substrate; all other substrates tested exhibited less than 25% of the activity observed with mannitol-1-phosphate."} {"id": "PMID:179690", "title": "Wilms' tumour: adjuvant treatment with actinomycin D and vincristine.", "content": "In an unselected series of 49 children with Wilms' tumour treated in 1969-74 the 5-year relapse-free survival and survival rates were 78% and 81%, respectively, whereas in the series of children treated in 1963-68 the corresponding rates were 49% and 70%. The significant improvement in the relapse-free survival rate was a result of adjuvant treatment with actinomycin D and vincristine (AMD + VCR), which, in some patients, eradicated occult metastatic disease. In the treatment of lung metastases the combination of whole-lung irradiation and maintained chemotherapy with AMD + VCR proved excessively toxic: in 5 of 11 patients acute diffuse pneumonitis developed, and it was fatal in 3. Adjuvant AMD + VCR therapy is advocated in all patients with Wilms' tumour except children less than 12 months old with a tumour of moderate size, limited to the kidney and completely resectable.", "contents": "Wilms' tumour: adjuvant treatment with actinomycin D and vincristine. In an unselected series of 49 children with Wilms' tumour treated in 1969-74 the 5-year relapse-free survival and survival rates were 78% and 81%, respectively, whereas in the series of children treated in 1963-68 the corresponding rates were 49% and 70%. The significant improvement in the relapse-free survival rate was a result of adjuvant treatment with actinomycin D and vincristine (AMD + VCR), which, in some patients, eradicated occult metastatic disease. In the treatment of lung metastases the combination of whole-lung irradiation and maintained chemotherapy with AMD + VCR proved excessively toxic: in 5 of 11 patients acute diffuse pneumonitis developed, and it was fatal in 3. Adjuvant AMD + VCR therapy is advocated in all patients with Wilms' tumour except children less than 12 months old with a tumour of moderate size, limited to the kidney and completely resectable."} {"id": "PMID:179692", "title": "Chorionic gonadotropin.", "content": "One of the most exciting and useful developments in modern oncology has been the recognition that certain biochemical tags can be used as cell markers in diagnosis, in monitoring the effects of anti-tumor therapy, and in follow-up to detect tumor recurrence. The measurement of chorionic gonadotropin (CG) in women with choriocarcinoma and/or gestational trophoblastic disease was the first test that could be relied upon entirely for this purpose. Furthermore, the amount of functional neoplastic tissue could be approximated by determining the production rate of this hormone which in normal physiologic conditions is only produced by syncytiotrophoblasts. The measurement of CG is now similarly used for the management of patients (both male and female) with choriocarcinoma originating in the tests and ovary. More recently a wide variety of nontrophoblastic malignant neoplasms have also been shown to produce CG, presumably from primitive tumor cells. Work is currently underway to ascertain the extent and potential usefulness of this observation in a wide variety of tumor systems, in the hope that improved tumor monitoring might be achieved.", "contents": "Chorionic gonadotropin. One of the most exciting and useful developments in modern oncology has been the recognition that certain biochemical tags can be used as cell markers in diagnosis, in monitoring the effects of anti-tumor therapy, and in follow-up to detect tumor recurrence. The measurement of chorionic gonadotropin (CG) in women with choriocarcinoma and/or gestational trophoblastic disease was the first test that could be relied upon entirely for this purpose. Furthermore, the amount of functional neoplastic tissue could be approximated by determining the production rate of this hormone which in normal physiologic conditions is only produced by syncytiotrophoblasts. The measurement of CG is now similarly used for the management of patients (both male and female) with choriocarcinoma originating in the tests and ovary. More recently a wide variety of nontrophoblastic malignant neoplasms have also been shown to produce CG, presumably from primitive tumor cells. Work is currently underway to ascertain the extent and potential usefulness of this observation in a wide variety of tumor systems, in the hope that improved tumor monitoring might be achieved."} {"id": "PMID:179693", "title": "Hormones and gynecologic cancer.", "content": "Available basic information about the regulation of rates of production, blood levels, intracellular metabolism, and action of steroid hormones and prolactin is reviewed and related to high-risk factors and therapeutic procedures applicable to gynecologic cancer.", "contents": "Hormones and gynecologic cancer. Available basic information about the regulation of rates of production, blood levels, intracellular metabolism, and action of steroid hormones and prolactin is reviewed and related to high-risk factors and therapeutic procedures applicable to gynecologic cancer."} {"id": "PMID:179694", "title": "Viruses and cancer of the lower genital tract.", "content": "The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV-2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV-2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer.", "contents": "Viruses and cancer of the lower genital tract. The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV-2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV-2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer."} {"id": "PMID:179695", "title": "Current status of treatment of gestational trophoblastic disease.", "content": "A brief summary is given of the developments leading to the current status of treatment of gestational trophoblastic neoplasms, both nonmetastatic and metastatic. Hydatidiform mole has been identified as the precursor type of pregnancy in approximately 50% of those women developing metastatic disease. The other half developed this as consequences of either a full-term delivery or some type of abortion. Sensitive assays for human chorionic gonadotropin (HCG) are needed in the diagnosis, management, and follow-up of these patients. Current therapy is outlined: nonmetastatic disease receives single agent chemotherapy with methotrexate or actinomycin D, with approximately 100% cure and 90% retention of reproductive function; metastatic disease, \"low risk\", receives single agent chemotherapy with the same drugs, with an expected cure rate of 95-100%; metastatic disease, \"high risk\", receives initial therapy with multiple agent chemotherapy, with a cure rate of approximately 75%. Current unresolved questions are discussed briefly.", "contents": "Current status of treatment of gestational trophoblastic disease. A brief summary is given of the developments leading to the current status of treatment of gestational trophoblastic neoplasms, both nonmetastatic and metastatic. Hydatidiform mole has been identified as the precursor type of pregnancy in approximately 50% of those women developing metastatic disease. The other half developed this as consequences of either a full-term delivery or some type of abortion. Sensitive assays for human chorionic gonadotropin (HCG) are needed in the diagnosis, management, and follow-up of these patients. Current therapy is outlined: nonmetastatic disease receives single agent chemotherapy with methotrexate or actinomycin D, with approximately 100% cure and 90% retention of reproductive function; metastatic disease, \"low risk\", receives single agent chemotherapy with the same drugs, with an expected cure rate of 95-100%; metastatic disease, \"high risk\", receives initial therapy with multiple agent chemotherapy, with a cure rate of approximately 75%. Current unresolved questions are discussed briefly."} {"id": "PMID:179696", "title": "Herpes simplex virus-specific antigens in exfoliated cervical cells from women with and without cervical anaplasia.", "content": "By the indirect immunofluorescence technique the presence of herpes simplex virus-specific antigens was investigated in cervical cells of 530 women with normal cervical epithelium, 175 with bland disorders, 52 with dysplasias, and 38 with invasive cervical carcinomas of the uterine cervix. Antigens were present in 9% of samples from women with normal cervical epithelium; they were present in 41% of the samples from women with bland disorders, 61% of those from dysplasia patients, and 94% of those from invasive carcinoma patients. The testing of 3 consecutive imprints of 68 antigen-positive and 232 antigen-negative women at 6-month intervals revealed that, in cervical cells, herpesvirus-specific antigens persisted throughout the 1-year period of the follow-up.", "contents": "Herpes simplex virus-specific antigens in exfoliated cervical cells from women with and without cervical anaplasia. By the indirect immunofluorescence technique the presence of herpes simplex virus-specific antigens was investigated in cervical cells of 530 women with normal cervical epithelium, 175 with bland disorders, 52 with dysplasias, and 38 with invasive cervical carcinomas of the uterine cervix. Antigens were present in 9% of samples from women with normal cervical epithelium; they were present in 41% of the samples from women with bland disorders, 61% of those from dysplasia patients, and 94% of those from invasive carcinoma patients. The testing of 3 consecutive imprints of 68 antigen-positive and 232 antigen-negative women at 6-month intervals revealed that, in cervical cells, herpesvirus-specific antigens persisted throughout the 1-year period of the follow-up."} {"id": "PMID:179697", "title": "Variation in glycosaminoglycan components of breast tumors.", "content": "The correlation between the content of individual glycosaminoglycans and the histological patterns are studied on breast tumor tissues. The myxomatous stroma of intracanalicular fibroadenoma contained a large amount of glycosaminoglycans, which were mainly hyaluronic acid. The chondroitin 4- and 6-sulfate level was also high. As the supporting stroma of this tumor became denser and more fibrous, the level of hyaluronic acid content was reduced. In the case of pericanalicular fibroadenoma, glycosaminoglycans were small in amount and the levels of hyaluronic acid and chondroitin sulfate were low, but the ratio of dermatan sulfate content was higher. In the case of gynecomastia, the conent was almost the same as that of pericanalicular fibroadenoma. Scirrhous carcinoma tissues contained a relatively large amount of hyaluronic acid and chondroitin sulfate. No remarkable differences in heparan sulfate content were observed in any one of the breast tumors tested. Dermatan sulfate-chondroitin sulfate copolymers were detected in all the tumors. The presence of dermatan sulfate seemed to have an intimate relation with the fibrogenesis in the interstitial stromal element of the tumor tissues.", "contents": "Variation in glycosaminoglycan components of breast tumors. The correlation between the content of individual glycosaminoglycans and the histological patterns are studied on breast tumor tissues. The myxomatous stroma of intracanalicular fibroadenoma contained a large amount of glycosaminoglycans, which were mainly hyaluronic acid. The chondroitin 4- and 6-sulfate level was also high. As the supporting stroma of this tumor became denser and more fibrous, the level of hyaluronic acid content was reduced. In the case of pericanalicular fibroadenoma, glycosaminoglycans were small in amount and the levels of hyaluronic acid and chondroitin sulfate were low, but the ratio of dermatan sulfate content was higher. In the case of gynecomastia, the conent was almost the same as that of pericanalicular fibroadenoma. Scirrhous carcinoma tissues contained a relatively large amount of hyaluronic acid and chondroitin sulfate. No remarkable differences in heparan sulfate content were observed in any one of the breast tumors tested. Dermatan sulfate-chondroitin sulfate copolymers were detected in all the tumors. The presence of dermatan sulfate seemed to have an intimate relation with the fibrogenesis in the interstitial stromal element of the tumor tissues."} {"id": "PMID:179698", "title": "Biochemistry and enzyme induction in MC-29 virus-induced transplantable avian hepatoma.", "content": "For the biochemical characterization of a new transplantable hepatoma derived from the MC-29 virus-induced liver tumor, the macromolecular content and the inducibility of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and aryl hydrocarbon hydroxylase were compared in chicken liver and in this hepatoma. The alteration of the nucleocytoplasmic ratio was deduced from measurements of DNA, RNA, protein, and phospholipid contents of the whole cell homogenate and cell fractions. The increased nuclear and decreased cytoplasmic content of macromolecules suggests a dominancy of the nuclei in the tumor cells. Glucose-6-phosphatase and aryl hydrocarbon hydroxylase activities were lower by 60 and 80%, respectively, in the highly proliferating hepatoma than in the liver. In contrast, glucose-6-phosphate dehydrogenase activity increased in the hepatoma. However, enzyme inducers, such as methylcholanthrene, hydrocortisone, and insulin, were able to enhance the activity of these enzymes in the liver but had no stimulating effect on the hepatoma.", "contents": "Biochemistry and enzyme induction in MC-29 virus-induced transplantable avian hepatoma. For the biochemical characterization of a new transplantable hepatoma derived from the MC-29 virus-induced liver tumor, the macromolecular content and the inducibility of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and aryl hydrocarbon hydroxylase were compared in chicken liver and in this hepatoma. The alteration of the nucleocytoplasmic ratio was deduced from measurements of DNA, RNA, protein, and phospholipid contents of the whole cell homogenate and cell fractions. The increased nuclear and decreased cytoplasmic content of macromolecules suggests a dominancy of the nuclei in the tumor cells. Glucose-6-phosphatase and aryl hydrocarbon hydroxylase activities were lower by 60 and 80%, respectively, in the highly proliferating hepatoma than in the liver. In contrast, glucose-6-phosphate dehydrogenase activity increased in the hepatoma. However, enzyme inducers, such as methylcholanthrene, hydrocortisone, and insulin, were able to enhance the activity of these enzymes in the liver but had no stimulating effect on the hepatoma."} {"id": "PMID:179699", "title": "Electrophysiological properties of ethylnitrosourea-induced, neoplastic neurogenic rat cell lines cultured in vitro and in vivo.", "content": "A comparative analysis was performed on the electrophysiological properties of 11 neoplastic neurogenic cell culture lines and five other cell lines of different origin (HV1C, rat bile duct carcinoma; BICR/M1RK, rat mammary tumor; HeLa, human cervix carcinoma; 3T3, mouse embryo; REe, rat embryo). Neurogenic lines were derived either from N-ethyl-N-nitrosourea-induced neoplasms of the nervous system or from cultured fetal rat brain cells that had undergone neoplastic transformation in vitro after exposure to N-ethyl-N-nitrosourea in vivo. Electrical membrane excitability was lacking in all neurogenic cells analyzed. Their membrane potential and input resistance values were similar to those of the nonneurogenic lines. Intercellular ionic coupling was consistently observed between cells of a fibroblastoid shape or cells bearing multiple cytoplasmic processes (i.e., all neurogenic lines HV1C, BICR/M1RK, and 3T3). Epithelioid cells (i.e., HeLa, REe, an NV1C subpopulation, and a GV1C1 variant) showed no such intercellular communication. In vivo monolayer cultures on glass coverslips were obtained by a modified i.p. diffusion chamber technique. Under these conditions, the cells (with the exception of a glioma-derived cell line) retained the morphological appearance and electrophysiological properties observed in vitro.", "contents": "Electrophysiological properties of ethylnitrosourea-induced, neoplastic neurogenic rat cell lines cultured in vitro and in vivo. A comparative analysis was performed on the electrophysiological properties of 11 neoplastic neurogenic cell culture lines and five other cell lines of different origin (HV1C, rat bile duct carcinoma; BICR/M1RK, rat mammary tumor; HeLa, human cervix carcinoma; 3T3, mouse embryo; REe, rat embryo). Neurogenic lines were derived either from N-ethyl-N-nitrosourea-induced neoplasms of the nervous system or from cultured fetal rat brain cells that had undergone neoplastic transformation in vitro after exposure to N-ethyl-N-nitrosourea in vivo. Electrical membrane excitability was lacking in all neurogenic cells analyzed. Their membrane potential and input resistance values were similar to those of the nonneurogenic lines. Intercellular ionic coupling was consistently observed between cells of a fibroblastoid shape or cells bearing multiple cytoplasmic processes (i.e., all neurogenic lines HV1C, BICR/M1RK, and 3T3). Epithelioid cells (i.e., HeLa, REe, an NV1C subpopulation, and a GV1C1 variant) showed no such intercellular communication. In vivo monolayer cultures on glass coverslips were obtained by a modified i.p. diffusion chamber technique. Under these conditions, the cells (with the exception of a glioma-derived cell line) retained the morphological appearance and electrophysiological properties observed in vitro."} {"id": "PMID:179700", "title": "Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat.", "content": "It was previously reported that the properties of alcohol dehydrogenase of a rat hepatocellular carcinoma (Becker H-252), a tumor of intermediate growth rate, were different from those of the liver enzyme, suggesting different isozymes. To determine whether the degree of differentiation affected the isozyme of alcohol dehydrogenase, a fast-growing, poorly differentiated tumor and one that is well differentiated and of intermediate growth rate were studied. Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition. By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme. Thus, alcohol dehydrogenase is another example of an enzyme the isozyme composition of which changes with neoplastic de-differentiation. Further studies, including gel electrophoresis, substrate specificity patterns, and interaction with antibodies to alcohol dehydrogenase, are required to determine the factors responsible for the biochemical defect that occurs at the molecular level during carcinogenesis and whether the alcohol dehydrogenase isozymes in the Becker H-252 and Morris 7288ctc hepatomas are identical. A survey of several normal rat tissues revealed that only the stomach contains this unique isozyme of alcohol dehydrogenase.", "contents": "Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat. It was previously reported that the properties of alcohol dehydrogenase of a rat hepatocellular carcinoma (Becker H-252), a tumor of intermediate growth rate, were different from those of the liver enzyme, suggesting different isozymes. To determine whether the degree of differentiation affected the isozyme of alcohol dehydrogenase, a fast-growing, poorly differentiated tumor and one that is well differentiated and of intermediate growth rate were studied. Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition. By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme. Thus, alcohol dehydrogenase is another example of an enzyme the isozyme composition of which changes with neoplastic de-differentiation. Further studies, including gel electrophoresis, substrate specificity patterns, and interaction with antibodies to alcohol dehydrogenase, are required to determine the factors responsible for the biochemical defect that occurs at the molecular level during carcinogenesis and whether the alcohol dehydrogenase isozymes in the Becker H-252 and Morris 7288ctc hepatomas are identical. A survey of several normal rat tissues revealed that only the stomach contains this unique isozyme of alcohol dehydrogenase."} {"id": "PMID:179701", "title": "Binding of cyclic nucleotides with proteins in malignant and adenosine cyclic 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells in culture.", "content": "The binding of adenosine cyclic 3':5'-monophosphate (cyclic AMP) with soluble (100,000 X g supernatant), pellet, and total homogenate proteins from cyclic AMP-induced \"differentiated\" mouse neuroblastoma cells increased by about two-fold. The extent of binding with soluble proteins was higher than that with pellet proteins. The binding of cyclic AMP with soluble proteins from 5'-adenosine monophosphate-treated, serum-free medium-treated, sodium butyrate-treated, 6-thioguanine-treated, or X-irradiated neuroblastoma cells did not significantly change. When the soluble proteins containing bound cyclic [3H]AMP were filtered through a Sephadex G-25 column, the relative amount of protein-bound cyclic [3H]AMP in differentiated cells was greater than that in malignant cells, but the amount of free cyclic [3H]AMP was correspondingly less. The electrophoretic characteristics of cyclic AMP-binding proteins of differentiated and malignant cells were identical. There were two binding peaks, but the extent of binding at each peak was relatively high in differentiated neuroblastoma cells. An increase in cyclic AMP binding occurred 24 hr after treatment of neuroblastoma cells with prostaglandin E1. This increase was completely blocked by cycloheximide but not by actinomycin D. The binding was heat labile and sensitive to protease action. These data indicate that the increase in binding in differentiated cells is due to an elevation in the levels of binding proteins. The binding of cyclic AMP with soluble proteins from rat glial cells and mouse L-cells did not significantly change after treatment with prostaglandin E1 or an inhibitor of cyclic AMP phosphodiesterase. Cyclic AMP and guanosine cyclic 3':5'-monophosphate bind with the same proteins, but cyclic AMP has about 10-fold higher binding affinity than does guanosine cyclic 3':5'-monophosphate.", "contents": "Binding of cyclic nucleotides with proteins in malignant and adenosine cyclic 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells in culture. The binding of adenosine cyclic 3':5'-monophosphate (cyclic AMP) with soluble (100,000 X g supernatant), pellet, and total homogenate proteins from cyclic AMP-induced \"differentiated\" mouse neuroblastoma cells increased by about two-fold. The extent of binding with soluble proteins was higher than that with pellet proteins. The binding of cyclic AMP with soluble proteins from 5'-adenosine monophosphate-treated, serum-free medium-treated, sodium butyrate-treated, 6-thioguanine-treated, or X-irradiated neuroblastoma cells did not significantly change. When the soluble proteins containing bound cyclic [3H]AMP were filtered through a Sephadex G-25 column, the relative amount of protein-bound cyclic [3H]AMP in differentiated cells was greater than that in malignant cells, but the amount of free cyclic [3H]AMP was correspondingly less. The electrophoretic characteristics of cyclic AMP-binding proteins of differentiated and malignant cells were identical. There were two binding peaks, but the extent of binding at each peak was relatively high in differentiated neuroblastoma cells. An increase in cyclic AMP binding occurred 24 hr after treatment of neuroblastoma cells with prostaglandin E1. This increase was completely blocked by cycloheximide but not by actinomycin D. The binding was heat labile and sensitive to protease action. These data indicate that the increase in binding in differentiated cells is due to an elevation in the levels of binding proteins. The binding of cyclic AMP with soluble proteins from rat glial cells and mouse L-cells did not significantly change after treatment with prostaglandin E1 or an inhibitor of cyclic AMP phosphodiesterase. Cyclic AMP and guanosine cyclic 3':5'-monophosphate bind with the same proteins, but cyclic AMP has about 10-fold higher binding affinity than does guanosine cyclic 3':5'-monophosphate."} {"id": "PMID:179702", "title": "Differences between pyrimidine nucleoside monophosphate kinase from rat Novikoff ascites hepatoma and rat liver.", "content": "Pyrimidine nucleoside monophosphate kinase [deoxycytidine monophosphate:adenosine triphosphate (dCMP:ATP) phosphotransferase. EC 2.7.4.14] has been purified from rat Novikoff ascites hepatoma and rat liver, each to a single major band appearing on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Differences exist in regard to efficiency and regulation of enzymatic activities. The Km values of the tumor kinase for cytidine monophosphate (CMP) (0.0053 +/- 0.0008 MM) and dCMP (0.715 +/- 0.068 MM) are approximately one-fourth the Km values of the rat liver kinase, for CMP (0.030 +/- 0.007 MM) and dCMP (2.77 +/- 0.39 MM). The tumor dCMP kinase exhibits a lower Km for ATP (0.134 +/- 0.008 MM) than the rat liver kinase (0.68 +/- 0.09 mM). Moreover, the dCMP:CMP kinase activity ratio for the tumor enzyme is 1.12, while that for the rat liver enzyme is 0.45. The uridine monophosphate:CMP kinase activity ratio for the tumor enzyme is 1.93, while that for the rat liver enzyme is 2.68. Lower concentrations of dithiothreitol are required for 50% reactivation of the tumor dCMP kinase (1.00 mM) and CMP kinase (0.10 mM) than rat liver dCMP kinase (2.20 mM) and CMP kinase (0.57 mM). Thus, the kinase from Novikoff hepatoma exhibits properties of increased efficiency and relaxed regulation of activity which render it more suitable for a tumor, in which active DNA synthesis is ongoing.", "contents": "Differences between pyrimidine nucleoside monophosphate kinase from rat Novikoff ascites hepatoma and rat liver. Pyrimidine nucleoside monophosphate kinase [deoxycytidine monophosphate:adenosine triphosphate (dCMP:ATP) phosphotransferase. EC 2.7.4.14] has been purified from rat Novikoff ascites hepatoma and rat liver, each to a single major band appearing on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Differences exist in regard to efficiency and regulation of enzymatic activities. The Km values of the tumor kinase for cytidine monophosphate (CMP) (0.0053 +/- 0.0008 MM) and dCMP (0.715 +/- 0.068 MM) are approximately one-fourth the Km values of the rat liver kinase, for CMP (0.030 +/- 0.007 MM) and dCMP (2.77 +/- 0.39 MM). The tumor dCMP kinase exhibits a lower Km for ATP (0.134 +/- 0.008 MM) than the rat liver kinase (0.68 +/- 0.09 mM). Moreover, the dCMP:CMP kinase activity ratio for the tumor enzyme is 1.12, while that for the rat liver enzyme is 0.45. The uridine monophosphate:CMP kinase activity ratio for the tumor enzyme is 1.93, while that for the rat liver enzyme is 2.68. Lower concentrations of dithiothreitol are required for 50% reactivation of the tumor dCMP kinase (1.00 mM) and CMP kinase (0.10 mM) than rat liver dCMP kinase (2.20 mM) and CMP kinase (0.57 mM). Thus, the kinase from Novikoff hepatoma exhibits properties of increased efficiency and relaxed regulation of activity which render it more suitable for a tumor, in which active DNA synthesis is ongoing."} {"id": "PMID:179703", "title": "Pathology of lymphosarcoma in sheep induced with bovine leukemia virus.", "content": "Sixty-nine sheep were infected with bovine leukemia virus from bovine lymphosarcoma materials. Twenty-four developed lymphosarcoma and died from 13 to 66 (average, 29) months later. Circulating lymphocytes were increased to leukemia levels (70,000 to 403,000/cu mm blood) in only eight sheep within 2 to 3 months of death. Various lymph nodes and visceral organs including heart, abomasum, uterus, kidneys, and urinary tract were commonly affected as in cattle with the adult form of lymphosarcoma. In one sheep the skin was involved. The liver was involved in only one case. This was in contrast to more frequent involvement reported in literature for naturally occurring lymphosarcoma. The neoplasms in experimental sheep are regarded as a mixture of reticulum or histiocytic cells and lymphoid cells with transitional forms supported by a usually sparse and diffuse fibroplasia and a web of silver-staining reticulin fibers.", "contents": "Pathology of lymphosarcoma in sheep induced with bovine leukemia virus. Sixty-nine sheep were infected with bovine leukemia virus from bovine lymphosarcoma materials. Twenty-four developed lymphosarcoma and died from 13 to 66 (average, 29) months later. Circulating lymphocytes were increased to leukemia levels (70,000 to 403,000/cu mm blood) in only eight sheep within 2 to 3 months of death. Various lymph nodes and visceral organs including heart, abomasum, uterus, kidneys, and urinary tract were commonly affected as in cattle with the adult form of lymphosarcoma. In one sheep the skin was involved. The liver was involved in only one case. This was in contrast to more frequent involvement reported in literature for naturally occurring lymphosarcoma. The neoplasms in experimental sheep are regarded as a mixture of reticulum or histiocytic cells and lymphoid cells with transitional forms supported by a usually sparse and diffuse fibroplasia and a web of silver-staining reticulin fibers."} {"id": "PMID:179704", "title": "Experimental hepatocellular carcinogenesis.", "content": "The sequential development of lesions in the liver leading to hepatocellular carcinoma in experimental animals appears to follow a similar pattern irrespective of the carcinogen. The speed with which the lesions develop is related to the chemical, the dose and dosing schedule, and the diet fed. In studies with aflatoxin B1 there is a predictable series of morphological expressions beginning with focal areas of hydropic degeneration (Stage 1); hyperplastic basophilic cells, singly or in close association with Stage 1 (Stage 2); nodular hyperplasia of parenchymal cells which become progressively more abnormal (Stage 3); transitional cell changes (Stage 4); and, ultimatley, hepatocellular carcinoma (Stage 5).", "contents": "Experimental hepatocellular carcinogenesis. The sequential development of lesions in the liver leading to hepatocellular carcinoma in experimental animals appears to follow a similar pattern irrespective of the carcinogen. The speed with which the lesions develop is related to the chemical, the dose and dosing schedule, and the diet fed. In studies with aflatoxin B1 there is a predictable series of morphological expressions beginning with focal areas of hydropic degeneration (Stage 1); hyperplastic basophilic cells, singly or in close association with Stage 1 (Stage 2); nodular hyperplasia of parenchymal cells which become progressively more abnormal (Stage 3); transitional cell changes (Stage 4); and, ultimatley, hepatocellular carcinoma (Stage 5)."} {"id": "PMID:179705", "title": "Sex hormones and hepatic neoplasia.", "content": "The recent increase in hepatocellular neoplasms in women of child-bearing age taking oral contraceptives and in individuals of both sexes taking anabolic androgenic steroids is a phenomenon that requires urgent attention. Although most of the lesions are benign, reports of carcinomas in a few of these individuals and our own observation of an adenoma that shows borderline malignant transformation suggest that some of the adenomas are premalignant lesions. The pathology of our own cases and those reported in the literature are reviewed, and hypotheses are offered for a carcinogenic role of synthetic steroid sex hormones. These speculations are based on known toxic and metabolic actions of the drugs and are amenable to experimentation.", "contents": "Sex hormones and hepatic neoplasia. The recent increase in hepatocellular neoplasms in women of child-bearing age taking oral contraceptives and in individuals of both sexes taking anabolic androgenic steroids is a phenomenon that requires urgent attention. Although most of the lesions are benign, reports of carcinomas in a few of these individuals and our own observation of an adenoma that shows borderline malignant transformation suggest that some of the adenomas are premalignant lesions. The pathology of our own cases and those reported in the literature are reviewed, and hypotheses are offered for a carcinogenic role of synthetic steroid sex hormones. These speculations are based on known toxic and metabolic actions of the drugs and are amenable to experimentation."} {"id": "PMID:179706", "title": "Preneoplastic lesions in murine mammary cancer.", "content": "The current model for murine mammary tumorigenesis indicates that discrete, morphologically identifiable preneoplastic lesions precede and give rise to mammary tumors. The hyperplastic alveolar nodule is the primary lesion that precedes and gives rise to mammary tumors in mice infected with the mammary tumor virus (Bittner) or its variants. In mice fed 7,12-dimethylbenzanthracene or urethan, hyperplastic alveolar nodules are present but infrequent, and the major mammary dysplasias present are ductal hyperplasias. The ductal hyperplasias can be divided into four general morphological types: (a) simple terminal duct hyperplasia; (b) lobular hyperplasia; (c) papillary hyperplasia; (d) end-bud hyperplasia. All types of ductal hyperplasias are characterized by intraductal epithelial hyperplasia and have been shown to give rise to mammal adenocarcinomas in situ or by transplantation into the mammary gland-free fat pads of syngeneic mice. Our current hypothesis is that murine mammary cancer can evolve through one of several intermediate stages. The intermediate stages can be either alveolar or ductal hyperplasias. The latter resemble, in many instances, ductal lesions seen in human breast cancer.", "contents": "Preneoplastic lesions in murine mammary cancer. The current model for murine mammary tumorigenesis indicates that discrete, morphologically identifiable preneoplastic lesions precede and give rise to mammary tumors. The hyperplastic alveolar nodule is the primary lesion that precedes and gives rise to mammary tumors in mice infected with the mammary tumor virus (Bittner) or its variants. In mice fed 7,12-dimethylbenzanthracene or urethan, hyperplastic alveolar nodules are present but infrequent, and the major mammary dysplasias present are ductal hyperplasias. The ductal hyperplasias can be divided into four general morphological types: (a) simple terminal duct hyperplasia; (b) lobular hyperplasia; (c) papillary hyperplasia; (d) end-bud hyperplasia. All types of ductal hyperplasias are characterized by intraductal epithelial hyperplasia and have been shown to give rise to mammal adenocarcinomas in situ or by transplantation into the mammary gland-free fat pads of syngeneic mice. Our current hypothesis is that murine mammary cancer can evolve through one of several intermediate stages. The intermediate stages can be either alveolar or ductal hyperplasias. The latter resemble, in many instances, ductal lesions seen in human breast cancer."} {"id": "PMID:179708", "title": "Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide and its metabolites on Novikoff hepatoma cells.", "content": "Studies were undertaken to determine the effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and its metabolites on the growth and macromolecular synthesis of Novikoff hepatoma cells in culture. DTIC (3.0 mM) in light decreased the viable cell count by 90% within 96 hr. DTIC protected from light, 2-azahypoxanthine, dimethylamine, and 5-aminoimidazole-4-carboxamide, all at 3.0 mM, reduced the rate of cellular proliferation. 5-Diazoimidazole-4-carboxamide (1.0 mM) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (3.0 mM) decreased the viable cell count by 99%. Effects on macromolecular synthesis were determined by the rate of incorporation of the appropriate 3H-labeled precursor. Results after 6 hr are given as percentage of controls. DTIC (1.0 mM) in light inhibited DNA (8%), RNA (41%), and protein (63%) synthesis. DTIC (1.0 mM) protected from light inhibited DNA (12%) and RNA (57%) synthesis. 5-Diazoimidazole-4-carboxamide (0.1 mM) inhibited DNA (1%), RNA (9%), and protein (1%) synthesis. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (1.0 mM) inhibited DNA (72%) and protein (65%) synthesis but stimulated RNA (127%) synthesis. 2-Azahypoxanthine (1.0 mM) inhibited DNA (43%), RNA 82%) and protein (28%) synthesis. 5-Aminoimidazole-4-carboxamide (3.0 mM) stimulated DNA (354%) and RNA (266%) synthesis. These data show that DTIC is able to generate several toxic metabolites that may be responsible for its biological effects.", "contents": "Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide and its metabolites on Novikoff hepatoma cells. Studies were undertaken to determine the effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and its metabolites on the growth and macromolecular synthesis of Novikoff hepatoma cells in culture. DTIC (3.0 mM) in light decreased the viable cell count by 90% within 96 hr. DTIC protected from light, 2-azahypoxanthine, dimethylamine, and 5-aminoimidazole-4-carboxamide, all at 3.0 mM, reduced the rate of cellular proliferation. 5-Diazoimidazole-4-carboxamide (1.0 mM) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (3.0 mM) decreased the viable cell count by 99%. Effects on macromolecular synthesis were determined by the rate of incorporation of the appropriate 3H-labeled precursor. Results after 6 hr are given as percentage of controls. DTIC (1.0 mM) in light inhibited DNA (8%), RNA (41%), and protein (63%) synthesis. DTIC (1.0 mM) protected from light inhibited DNA (12%) and RNA (57%) synthesis. 5-Diazoimidazole-4-carboxamide (0.1 mM) inhibited DNA (1%), RNA (9%), and protein (1%) synthesis. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (1.0 mM) inhibited DNA (72%) and protein (65%) synthesis but stimulated RNA (127%) synthesis. 2-Azahypoxanthine (1.0 mM) inhibited DNA (43%), RNA 82%) and protein (28%) synthesis. 5-Aminoimidazole-4-carboxamide (3.0 mM) stimulated DNA (354%) and RNA (266%) synthesis. These data show that DTIC is able to generate several toxic metabolites that may be responsible for its biological effects."} {"id": "PMID:179709", "title": "Autogenous immunity to mouse mammary tumor virus in mouse strains of high and low mammary tumor incidence.", "content": "Specific radioimmune precipitation assays were utilized to demonstrate the presence of precipitating antibodies to mouse mammary tumor virus (MMTV) in the high-spontaneous mammary tumor strains of mice: C3H/HeN+, GR/N, BALB/cfC3H, and C57BL/6 X C3H F1 (hereafter called B6C3F1). Antibody titers in C3H/HeN+ mice increased with age, with highest titers observed in tumor-bearing animals. MMTV-precipitating antibodies were not detectable by radioimmune precipitation assay in low-mammary tumor strains (AKR, BALB/c C57BL/6, and C3H/HeN-) but were detectable in MMTV-inoculated BALB/c mice. Appearance of antibodies preceded palpable tumor formation, and antibody titers were directly correlated to virus dose. Natural antibody to MMTV in C3H/HeN+ and B6C3F1 mice coexists with the murine leukemia virus natural antibody as determined by competition radioimmunoassays.", "contents": "Autogenous immunity to mouse mammary tumor virus in mouse strains of high and low mammary tumor incidence. Specific radioimmune precipitation assays were utilized to demonstrate the presence of precipitating antibodies to mouse mammary tumor virus (MMTV) in the high-spontaneous mammary tumor strains of mice: C3H/HeN+, GR/N, BALB/cfC3H, and C57BL/6 X C3H F1 (hereafter called B6C3F1). Antibody titers in C3H/HeN+ mice increased with age, with highest titers observed in tumor-bearing animals. MMTV-precipitating antibodies were not detectable by radioimmune precipitation assay in low-mammary tumor strains (AKR, BALB/c C57BL/6, and C3H/HeN-) but were detectable in MMTV-inoculated BALB/c mice. Appearance of antibodies preceded palpable tumor formation, and antibody titers were directly correlated to virus dose. Natural antibody to MMTV in C3H/HeN+ and B6C3F1 mice coexists with the murine leukemia virus natural antibody as determined by competition radioimmunoassays."} {"id": "PMID:179710", "title": "Changes in transfer RNA's in human malignant trophoblastic cells (BeWo line).", "content": "Ten aminoacyl transfer RNA's prepared from human malignant trophoblastic cells (BeWo line) were compared with the corresponding aminoacyl transfer RNA's from normal human chorionic tissue by cochromatography on a RPC-5 column. Phenylalanyl transfer RNA (Phe-tRNA) of BeWo cells had, in addition to the single species of Phe-tRNA found in normal chorionic tissues, an early eluting component. When Phe-tRNA from the chorion was exposed to mild acid, which selectively excises the Y base, it eluted in the same position as the early eluting Phe-tRNA of BeWo cells. Therefore, the BeWo Phe-tRNA is partially undermodified. Tyrosyl transfer RNA of BeWo cells exhibited a broad-based peak which eluted later than the normal and probably consists of two or more tyrosyl transfer RNA's. Seryl transfer RNA of BeWo cells showed two peaks of acceptor activity, while seryl transfer RNA of normal chorion had a third peak that eluted at a higher salt concentration. In addition, in an early eluting methionyl and lysyl transfer RNA and in a late eluting arginyl transfer RNA from BeWo cells and normal charion, quantitative alterations were detected. The remaining four transfer RNA's, leucyl, aspartyl, valyl, and histidyl, from the two sources did not show any significant differences in elution profiles. These alterations of the chromatographic profile appeared to be due to new or altered species of transfer RNA. They were not due to differences in the aminoacyl transfer RNA synthetase. The transfer RNA methyltransferase capacity of the enzymes from BeWo cells was 2-fold higher than that of the enzymes extracted from the chorion.", "contents": "Changes in transfer RNA's in human malignant trophoblastic cells (BeWo line). Ten aminoacyl transfer RNA's prepared from human malignant trophoblastic cells (BeWo line) were compared with the corresponding aminoacyl transfer RNA's from normal human chorionic tissue by cochromatography on a RPC-5 column. Phenylalanyl transfer RNA (Phe-tRNA) of BeWo cells had, in addition to the single species of Phe-tRNA found in normal chorionic tissues, an early eluting component. When Phe-tRNA from the chorion was exposed to mild acid, which selectively excises the Y base, it eluted in the same position as the early eluting Phe-tRNA of BeWo cells. Therefore, the BeWo Phe-tRNA is partially undermodified. Tyrosyl transfer RNA of BeWo cells exhibited a broad-based peak which eluted later than the normal and probably consists of two or more tyrosyl transfer RNA's. Seryl transfer RNA of BeWo cells showed two peaks of acceptor activity, while seryl transfer RNA of normal chorion had a third peak that eluted at a higher salt concentration. In addition, in an early eluting methionyl and lysyl transfer RNA and in a late eluting arginyl transfer RNA from BeWo cells and normal charion, quantitative alterations were detected. The remaining four transfer RNA's, leucyl, aspartyl, valyl, and histidyl, from the two sources did not show any significant differences in elution profiles. These alterations of the chromatographic profile appeared to be due to new or altered species of transfer RNA. They were not due to differences in the aminoacyl transfer RNA synthetase. The transfer RNA methyltransferase capacity of the enzymes from BeWo cells was 2-fold higher than that of the enzymes extracted from the chorion."} {"id": "PMID:179711", "title": "Characteristics of cell membranes from somatic cell hybrids between rat hepatoma and mouse L-cells.", "content": "Cell membranes from mouse L-cells (L-B82), rat hepatoma (HTC-H1), and three clones of their somatic cell hybrids (07, V4a, and V5) showing different degrees of density-dependent inhibition of growth were analyzed by polyacrylamide gel electrophoresis. The membrane polypeptides of the hybrid clones were all similar and all showed higher proportions of polypeptides with molecular weights of 56,000 and 45,000 than their parents of their normal counterparts. The major glycoprotein form cell hybrids appeared to be identical with that of rat liver or rat hepatoma cells and different from that of L-cells. One hybrid showed density-dependent inhibition growth; the other two, like both parents, did not. All produced tumors in nude mice, although tumor production by the hybrids was delayed. A large external protein (M.W. 240,000) iodinated by lactoperoxidase-catalyzed reaction was virtually missing in the parents but was present at high levels in all their hybrid clones. Thus, there was a lack of correlation between the presence of this protein, growth control in vitro, and tumorigenicity. Furthermore, no correlation was seen between agglutination of these cells by concanavalin A and tumorigenicity. The factors controlling these membrane properties thus are independent of density-dependent inhibition of growth and of those controlling the expression of cancer.", "contents": "Characteristics of cell membranes from somatic cell hybrids between rat hepatoma and mouse L-cells. Cell membranes from mouse L-cells (L-B82), rat hepatoma (HTC-H1), and three clones of their somatic cell hybrids (07, V4a, and V5) showing different degrees of density-dependent inhibition of growth were analyzed by polyacrylamide gel electrophoresis. The membrane polypeptides of the hybrid clones were all similar and all showed higher proportions of polypeptides with molecular weights of 56,000 and 45,000 than their parents of their normal counterparts. The major glycoprotein form cell hybrids appeared to be identical with that of rat liver or rat hepatoma cells and different from that of L-cells. One hybrid showed density-dependent inhibition growth; the other two, like both parents, did not. All produced tumors in nude mice, although tumor production by the hybrids was delayed. A large external protein (M.W. 240,000) iodinated by lactoperoxidase-catalyzed reaction was virtually missing in the parents but was present at high levels in all their hybrid clones. Thus, there was a lack of correlation between the presence of this protein, growth control in vitro, and tumorigenicity. Furthermore, no correlation was seen between agglutination of these cells by concanavalin A and tumorigenicity. The factors controlling these membrane properties thus are independent of density-dependent inhibition of growth and of those controlling the expression of cancer."} {"id": "PMID:179712", "title": "Studies on the selective action of cyclophosphamide (NSC-26271): Inactivation of the hydroxylated metabolite by tissue-soluble enzymes.", "content": "The hypothesis that selective action of cyclophosphamide, compared to other nitrogen mustards, is due to a balance between enzymatic formation of inactive metabolites and chemical formation of the alkylating product was studied in view of previous observation in our laboratory. Metabolite analysis, inhibition of growth of tumor cells in culture, and kinetic analysis of relevant enzyme activities were used in this investigation. The effect of tissue-soluble enzyme fractions on biochemically prepared aldophosphamide, aldophosphamide analogs, and phosphoramide mustard showed: (a) a range of deactivation abilities with aldophosphamide (liver greater than kidney greater than intestinal mucosa greater than tumor greater than spleen = bovine serum albumin solution); (b) the formation of different amounts of carboxyphosphamide from aldophosphamide; and (c) only comparatively small reductions in the toxicity of phosphoramide mustard and of 4-hydroxy-4methylcyclophosphamide. Correlations were found between NAD+-dependent aldehyde dehydrogenase activity and the deactivation ability of tissue-soluble enzyme fractions. Blockage (by C4 substitution) or inhibition (by disulfiram) of secondary oxidation of aldophosphamide, mediated by aldehyde dehydrogenase, resulted in diminished deactivation ability in vitro and reduced selectivity in vivo.", "contents": "Studies on the selective action of cyclophosphamide (NSC-26271): Inactivation of the hydroxylated metabolite by tissue-soluble enzymes. The hypothesis that selective action of cyclophosphamide, compared to other nitrogen mustards, is due to a balance between enzymatic formation of inactive metabolites and chemical formation of the alkylating product was studied in view of previous observation in our laboratory. Metabolite analysis, inhibition of growth of tumor cells in culture, and kinetic analysis of relevant enzyme activities were used in this investigation. The effect of tissue-soluble enzyme fractions on biochemically prepared aldophosphamide, aldophosphamide analogs, and phosphoramide mustard showed: (a) a range of deactivation abilities with aldophosphamide (liver greater than kidney greater than intestinal mucosa greater than tumor greater than spleen = bovine serum albumin solution); (b) the formation of different amounts of carboxyphosphamide from aldophosphamide; and (c) only comparatively small reductions in the toxicity of phosphoramide mustard and of 4-hydroxy-4methylcyclophosphamide. Correlations were found between NAD+-dependent aldehyde dehydrogenase activity and the deactivation ability of tissue-soluble enzyme fractions. Blockage (by C4 substitution) or inhibition (by disulfiram) of secondary oxidation of aldophosphamide, mediated by aldehyde dehydrogenase, resulted in diminished deactivation ability in vitro and reduced selectivity in vivo."} {"id": "PMID:179715", "title": "The effect of cyclic adenosine 3',5'-monophosphate on the uptake of estradiol by the neonatal mouse uterus: an autoradiographic study.", "content": "Uterine tissue from neonatal mice was incubated in vitro at 0 degrees C for 1 h in a medium containing 1 X 10(-8) M 3H-estradiol with or without 1 X 10(-4) M dibutyryl cyclic AMP. In some incubations the temperature was raised to 37 degrees C for 15 min after incubation in the cold, in others the temperature was kept at 0 degrees C during this 15 min period. The tissue was frozen in liquid propane cooled in liquid nitrogen, sectioned at 2 or 4 microns, and autoradiograms prepared according to the dry-mount procedure. cAMP increases the cellular uptake of 3H-estradiol in uterine tissue. After rising the temperature to 37 degrees C, grains appeared over the nuclei. cAMP at low temperature increased the cellular uptake of 3H-estradiol, but the grains were not associated with the nuclei. In the autoradiograms the grain number above the epithelium was markedly less than above the stroma.", "contents": "The effect of cyclic adenosine 3',5'-monophosphate on the uptake of estradiol by the neonatal mouse uterus: an autoradiographic study. Uterine tissue from neonatal mice was incubated in vitro at 0 degrees C for 1 h in a medium containing 1 X 10(-8) M 3H-estradiol with or without 1 X 10(-4) M dibutyryl cyclic AMP. In some incubations the temperature was raised to 37 degrees C for 15 min after incubation in the cold, in others the temperature was kept at 0 degrees C during this 15 min period. The tissue was frozen in liquid propane cooled in liquid nitrogen, sectioned at 2 or 4 microns, and autoradiograms prepared according to the dry-mount procedure. cAMP increases the cellular uptake of 3H-estradiol in uterine tissue. After rising the temperature to 37 degrees C, grains appeared over the nuclei. cAMP at low temperature increased the cellular uptake of 3H-estradiol, but the grains were not associated with the nuclei. In the autoradiograms the grain number above the epithelium was markedly less than above the stroma."} {"id": "PMID:179721", "title": "[Denitrifying bacteria of genus Alcaligenes isolated from soil].", "content": "The organism isolated is a small non-sporulating Gram-negative rod, motile by means of peritrichous flagellae. It is an oxidase-positive chemo-organotroph utilizing O2,NO-3,NO-2 and N2O as resiratory substrates. Primary alcohols as well as numerous organic and amino acids are utilized as carbon and energy sources. Carbohydrates are not assimilated. Poly-beta-hydroxybutyrate is accumulated intracellularly. The bacterium is assigned to the genus Alcaligenes and its phenotype characteristics are compared with those of A. faecalis.", "contents": "[Denitrifying bacteria of genus Alcaligenes isolated from soil]. The organism isolated is a small non-sporulating Gram-negative rod, motile by means of peritrichous flagellae. It is an oxidase-positive chemo-organotroph utilizing O2,NO-3,NO-2 and N2O as resiratory substrates. Primary alcohols as well as numerous organic and amino acids are utilized as carbon and energy sources. Carbohydrates are not assimilated. Poly-beta-hydroxybutyrate is accumulated intracellularly. The bacterium is assigned to the genus Alcaligenes and its phenotype characteristics are compared with those of A. faecalis."} {"id": "PMID:179722", "title": "Calcium accumulation and enzymatic activities of subcellular fractions from aortas and ventricles of genetically hypertensive rats.", "content": "Subcellular fractions were obtained from aortas and ventricles of 6-month-old spontaneously hypertensive and normotensive Wistar rats by the use of differential and sucrose density gradient centrifugation. These preparations were studied to determine what alterations in calcium accumulation and enzymatic activities might be associated with hypertension. The total amount of calcium accumulation (in the presence of ATP and 17 muM free calcium) by the plasma membrane-enriched fraction from hypertensive rat aortas significantly less than that from normotensive rats (11.3 +/- 0.4 vs 16.2 +/- 1.6 mumol of calcium/g of protein, n = 8). In contrast the specific activities of the plasma membrane marker enzymes, 5'-nucleotidase and phosphodiesterase I, were 80% and 40% greater, respectively, in the hypertensive than in the normotensive fractions. On the other hand, various fractions from ventricles of the two types of rats were generally similar in enzyme activities and calcium accumulation. The decreased rate of relaxation of aortas from spontaneously hypertensive rats may be caused by the decreased rate of calcium transport demonstrated in this study.", "contents": "Calcium accumulation and enzymatic activities of subcellular fractions from aortas and ventricles of genetically hypertensive rats. Subcellular fractions were obtained from aortas and ventricles of 6-month-old spontaneously hypertensive and normotensive Wistar rats by the use of differential and sucrose density gradient centrifugation. These preparations were studied to determine what alterations in calcium accumulation and enzymatic activities might be associated with hypertension. The total amount of calcium accumulation (in the presence of ATP and 17 muM free calcium) by the plasma membrane-enriched fraction from hypertensive rat aortas significantly less than that from normotensive rats (11.3 +/- 0.4 vs 16.2 +/- 1.6 mumol of calcium/g of protein, n = 8). In contrast the specific activities of the plasma membrane marker enzymes, 5'-nucleotidase and phosphodiesterase I, were 80% and 40% greater, respectively, in the hypertensive than in the normotensive fractions. On the other hand, various fractions from ventricles of the two types of rats were generally similar in enzyme activities and calcium accumulation. The decreased rate of relaxation of aortas from spontaneously hypertensive rats may be caused by the decreased rate of calcium transport demonstrated in this study."} {"id": "PMID:179723", "title": "Evaluation of 99mtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction.", "content": "Serial 99mTc pyrophosphate scintigrams were obtained 7 hr to 15 days after experimental acute myocardial infarction produced by permanent or transient coronary occlusion. Scintigrams were interpreted visually and the increased radioactivity in the precordial image was quantitated and compared to extent of infarction found histologically. Results of these studies indicate: 1) 99mTc pyrophosphate imaging is an extremely sensitive for detection of acute myocardial infarction, i.e., infarction in excess of 1% of the left ventricular mass was detected. 2) Early detection of acute infarction is a function of blood flow since 7 hr after infarction scans were negative after permanent occlusion but were strongly positive after transient occlusion. 3) Radioactivity in the precordial image was inversely related to extent of infarction after permanent occlusion and directly related to extent of infarction after transient occlusion. 4) 99mTc pyrophosphate localized in areas with significant histologic infarction but the distribution of radioactivity was not proportional to extent of infarction.", "contents": "Evaluation of 99mtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction. Serial 99mTc pyrophosphate scintigrams were obtained 7 hr to 15 days after experimental acute myocardial infarction produced by permanent or transient coronary occlusion. Scintigrams were interpreted visually and the increased radioactivity in the precordial image was quantitated and compared to extent of infarction found histologically. Results of these studies indicate: 1) 99mTc pyrophosphate imaging is an extremely sensitive for detection of acute myocardial infarction, i.e., infarction in excess of 1% of the left ventricular mass was detected. 2) Early detection of acute infarction is a function of blood flow since 7 hr after infarction scans were negative after permanent occlusion but were strongly positive after transient occlusion. 3) Radioactivity in the precordial image was inversely related to extent of infarction after permanent occlusion and directly related to extent of infarction after transient occlusion. 4) 99mTc pyrophosphate localized in areas with significant histologic infarction but the distribution of radioactivity was not proportional to extent of infarction."} {"id": "PMID:179724", "title": "Asthma due to non-occupational exposure to toluene (tolylene) di-isocyanate.", "content": "The production of asthma by toluene di-isocyanate, aspirated into the ventilating system and emanating from the exhausts of a neighbouring factory, was established in three otherwise non-exposed clerical workers. Occupational-type exposure tests with a polyurethane varnish/toluene di-isocyanate mixture elicited vigorous and prolonged non-immediate asthmatic reactions, thus enabling identification of the otherwise, obscure etiological cause of their asthma.", "contents": "Asthma due to non-occupational exposure to toluene (tolylene) di-isocyanate. The production of asthma by toluene di-isocyanate, aspirated into the ventilating system and emanating from the exhausts of a neighbouring factory, was established in three otherwise non-exposed clerical workers. Occupational-type exposure tests with a polyurethane varnish/toluene di-isocyanate mixture elicited vigorous and prolonged non-immediate asthmatic reactions, thus enabling identification of the otherwise, obscure etiological cause of their asthma."} {"id": "PMID:179732", "title": "Chromatography on Florisil in the quantitative estimation of urinary and other porphyrins.", "content": "We describe the use of Florisil chromatography to purify and fractionate porphyrins into uro-, copro-, and protoporphyrins before their measurement by quantitative fluorometry. Porphyrinogens in fresh urine may be rapidly oxidized to porphyrins by chloranil, or slowly in weakly alkaline solution, before the sample is applied to the Florisil column. Aliquots of the separate ammoniacal eluates may be lyophilized for additional fractionation by direct thin-layer chromatographic analysis if desired. The behavior of delta-aminolevulinic acid, porphobilinogen, and other pyrrole compounds in this system is also described.", "contents": "Chromatography on Florisil in the quantitative estimation of urinary and other porphyrins. We describe the use of Florisil chromatography to purify and fractionate porphyrins into uro-, copro-, and protoporphyrins before their measurement by quantitative fluorometry. Porphyrinogens in fresh urine may be rapidly oxidized to porphyrins by chloranil, or slowly in weakly alkaline solution, before the sample is applied to the Florisil column. Aliquots of the separate ammoniacal eluates may be lyophilized for additional fractionation by direct thin-layer chromatographic analysis if desired. The behavior of delta-aminolevulinic acid, porphobilinogen, and other pyrrole compounds in this system is also described."} {"id": "PMID:179733", "title": "Evaluation of adenosine 5'-monophosphate and fluoride as adenylate kinase inhibitors in the creatine kinase assay.", "content": "Adenylate kinase (EC 2.7.4.3) interferes positively in the serum creatine kinase (EC 2.7.3.2) assay when the rate of ATP production is monitored by a coupled enzyme system. A dual assay, measuring creatine kinase and adenylate kinase activity, was used to evaluate AMP and other possible adenylate kinase inhibitors that would permit specific measurement of creatine kinase activity in the presence of adenylate kinase. We found that AMP, routinely included in the creatine kinase assay system to inhibit adenylate kinase, partially inhibits both human serum creatine kinase and purified creatine kinase from rabbit muscle. The amount of creatine kinase inhibition is related directly to the AMP concentration and inversely to the substrate (ADP) concentration. We found that 25 mmol/liter of fluoride inhibits adenylate kinase without measurable effect on creatine kinase activity. We developed a serum creatine kinase assay including fluoride, and compared it with the dual assay system and with two commercial assay kits. Other halides or adenosine 2'-monophosphate did not selectively inhibit adenylate kinase.", "contents": "Evaluation of adenosine 5'-monophosphate and fluoride as adenylate kinase inhibitors in the creatine kinase assay. Adenylate kinase (EC 2.7.4.3) interferes positively in the serum creatine kinase (EC 2.7.3.2) assay when the rate of ATP production is monitored by a coupled enzyme system. A dual assay, measuring creatine kinase and adenylate kinase activity, was used to evaluate AMP and other possible adenylate kinase inhibitors that would permit specific measurement of creatine kinase activity in the presence of adenylate kinase. We found that AMP, routinely included in the creatine kinase assay system to inhibit adenylate kinase, partially inhibits both human serum creatine kinase and purified creatine kinase from rabbit muscle. The amount of creatine kinase inhibition is related directly to the AMP concentration and inversely to the substrate (ADP) concentration. We found that 25 mmol/liter of fluoride inhibits adenylate kinase without measurable effect on creatine kinase activity. We developed a serum creatine kinase assay including fluoride, and compared it with the dual assay system and with two commercial assay kits. Other halides or adenosine 2'-monophosphate did not selectively inhibit adenylate kinase."} {"id": "PMID:179734", "title": "Effect of reaction initiator on human lactate dehydrogenase assay.", "content": "Human lactate dehydrogenase isoenzymes I and V have decreased activities when the reaction is initiated with lactate. No loss in lactate dehydrogenase I activity was found when the reaction was initiated with enzyme or NAD+. For lactate dehydrogenase V an NAD+-initiated reaction, as compared to an enzyme-initiated reaction, yields lower activity in sodium pyrophosphate buffer but higher activity in tris(hydroxymethyl)aminomethane buffer. Both isoenzymes have higher lactate-to-pyruvate activity when assayed in the latter buffer than when assayed in the former. Human lactate dehydrogenase V (but not I) exhibited different activities when assayed with lactate from two different commercial sources. Human lactate dehydrogenase assayed by the pyruvate-to-lactate reaction is not affected by the choice of reaction initiator.", "contents": "Effect of reaction initiator on human lactate dehydrogenase assay. Human lactate dehydrogenase isoenzymes I and V have decreased activities when the reaction is initiated with lactate. No loss in lactate dehydrogenase I activity was found when the reaction was initiated with enzyme or NAD+. For lactate dehydrogenase V an NAD+-initiated reaction, as compared to an enzyme-initiated reaction, yields lower activity in sodium pyrophosphate buffer but higher activity in tris(hydroxymethyl)aminomethane buffer. Both isoenzymes have higher lactate-to-pyruvate activity when assayed in the latter buffer than when assayed in the former. Human lactate dehydrogenase V (but not I) exhibited different activities when assayed with lactate from two different commercial sources. Human lactate dehydrogenase assayed by the pyruvate-to-lactate reaction is not affected by the choice of reaction initiator."} {"id": "PMID:179735", "title": "Apoprotein profile of plasma and chylous ascites lipoproteins.", "content": "Plasma and chylous ascites lipoproteins were compared in a rare case of exudative enteropathy associated with stenosis of the thoracic duct. All ascites lipoproteins separated by ultracentrifugation showed a much higher triglyceride/protein ratio and a lower cholesterol ester content than their plasma counterparts. Polyarcylamide gel electrophoresis of apoproteins before and after fractionation on Sephadex G-200 essentially showed, compared to normal plasma, a reduction of apoprotein C in VLDL and HDL particularly obvious for apoCIII1 and CIII2. Ascites lipoproteins were characterized by an increased apoA content in chylomicrons, VLDL and LDL and a reduced percentage of apo CII and CIII1, mostly in chylomicrons, VLDL and HDL. The differences in composition between plasma and ascites might be explained by different origins for the various apoprotein subfractions. The transsudation of chyle into the abdominal cavity might divert some peptides of intestinal origin from their normal entry into the circulation.", "contents": "Apoprotein profile of plasma and chylous ascites lipoproteins. Plasma and chylous ascites lipoproteins were compared in a rare case of exudative enteropathy associated with stenosis of the thoracic duct. All ascites lipoproteins separated by ultracentrifugation showed a much higher triglyceride/protein ratio and a lower cholesterol ester content than their plasma counterparts. Polyarcylamide gel electrophoresis of apoproteins before and after fractionation on Sephadex G-200 essentially showed, compared to normal plasma, a reduction of apoprotein C in VLDL and HDL particularly obvious for apoCIII1 and CIII2. Ascites lipoproteins were characterized by an increased apoA content in chylomicrons, VLDL and LDL and a reduced percentage of apo CII and CIII1, mostly in chylomicrons, VLDL and HDL. The differences in composition between plasma and ascites might be explained by different origins for the various apoprotein subfractions. The transsudation of chyle into the abdominal cavity might divert some peptides of intestinal origin from their normal entry into the circulation."} {"id": "PMID:179736", "title": "Hepatic collagen proline hydroxylase activity in alcoholic liver disease.", "content": "The activity of hepatic collagen proline hydroxylase was examined in biopsy samples as a factor in collagen synthesis in 77 patients with alcoholic liver disease. The urinary excretion of peptide bound hydroxyproline was also measured in most of the patients, as an index of collagen degradation. The highest activities of collagen proline hydroxylase were found in the patients with alcoholic hepatitis. Enzyme activity was markedly increased in patients with non-specific changes on liver biopsy, whereas, patients with fatty infiltration had only mild elevations, and those with inactive cirrhosis had normal enzyme activity. Urinary hydroxyproline was elevated only in patients with alcoholic hepatitis and inactive cirrhosis. Follow-up determinations in 16 patients with alcoholic hepatitis, after 4 to 5 weeks, revealed a decrease in enzyme activity, but no change in urinary hydroxyproline. We conclude that among the types of alcohol-related liver diseases, alcoholic hepatitis is associated with the greatest turnover of hepatic collagen.", "contents": "Hepatic collagen proline hydroxylase activity in alcoholic liver disease. The activity of hepatic collagen proline hydroxylase was examined in biopsy samples as a factor in collagen synthesis in 77 patients with alcoholic liver disease. The urinary excretion of peptide bound hydroxyproline was also measured in most of the patients, as an index of collagen degradation. The highest activities of collagen proline hydroxylase were found in the patients with alcoholic hepatitis. Enzyme activity was markedly increased in patients with non-specific changes on liver biopsy, whereas, patients with fatty infiltration had only mild elevations, and those with inactive cirrhosis had normal enzyme activity. Urinary hydroxyproline was elevated only in patients with alcoholic hepatitis and inactive cirrhosis. Follow-up determinations in 16 patients with alcoholic hepatitis, after 4 to 5 weeks, revealed a decrease in enzyme activity, but no change in urinary hydroxyproline. We conclude that among the types of alcohol-related liver diseases, alcoholic hepatitis is associated with the greatest turnover of hepatic collagen."} {"id": "PMID:179737", "title": "Diagnosis of dyslipoprotein aemia by molecular sieve chromatography.", "content": "Agarose gel molecular sieve chromatography has been used as a tool in the diagnosis of dyslipoproteinaemias. The elution profile from control plasma contained three peaks, corresponding to very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). These accounted for 9.5%, 23.5% and 67% of the total lipoprotein absorption at 280 nm. Elution patterns from dyslipoproteinaemic serum showed alterations, not only in peak area, but also in peak migration rate through the agarose gel. These variations were reproducible and of such magnitude as to permit the use of molecular sieve chromatography as a tool in the diagnosis of dyslipoprotein-aemias of Type I, II (a + b), III, IV and V.", "contents": "Diagnosis of dyslipoprotein aemia by molecular sieve chromatography. Agarose gel molecular sieve chromatography has been used as a tool in the diagnosis of dyslipoproteinaemias. The elution profile from control plasma contained three peaks, corresponding to very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). These accounted for 9.5%, 23.5% and 67% of the total lipoprotein absorption at 280 nm. Elution patterns from dyslipoproteinaemic serum showed alterations, not only in peak area, but also in peak migration rate through the agarose gel. These variations were reproducible and of such magnitude as to permit the use of molecular sieve chromatography as a tool in the diagnosis of dyslipoprotein-aemias of Type I, II (a + b), III, IV and V."} {"id": "PMID:179738", "title": "Application of nicotinamide-adenine dinucleotide analogs for clinical enzymology: a spectrophotometric method for clinical analysis of lactate dehydrogenase patterns with the use of a nicotinamide-adenine dinucleotide analog.", "content": "The activities of porcine lactate dehydrogenase (LHD) isoenzymes were analyzed using nicotinamide-adenine dinucleotide (NAD) or its analogs as a cofactor, with varying concentrations of L-lactate from 13 to 530 mM. The greatest differences between H4-type and M4-type isoenzymes in reaction rates were observed when their activities were compared in a reaction mixture containing 530 mM lactate and NAD, and also in a system of 13 mM lactate with thionicotinamide-hypoxanthine dinucleotide as a cofactor. The ratio of the LDH activity exerted in the former reaction mixture to that exerted in the latter was termed the N/T value. The N/T values of porcine H4 and M4 isoenzymes were 0.49 and 9.33, respectively. The N/T values of other three isoenzymes (H3M1, H2M2 and H1M3) were calculated by assuming that the single subunits H1 and M1 contribute one-fourth of the values of 0.49 and 9.33, respectively, and a given isoenzyme which is a combination of four subunits of H and M comprises the sum of their values. The calculated values agreed fairly well with the experimental results. The N/T value method was found to be applicable to human LDH isoenzymes, and sera from various patients were analyzed in comparison with hormonal sera. The method is particularly suitable for the numerical expression of LDH isoenzyme profiles.", "contents": "Application of nicotinamide-adenine dinucleotide analogs for clinical enzymology: a spectrophotometric method for clinical analysis of lactate dehydrogenase patterns with the use of a nicotinamide-adenine dinucleotide analog. The activities of porcine lactate dehydrogenase (LHD) isoenzymes were analyzed using nicotinamide-adenine dinucleotide (NAD) or its analogs as a cofactor, with varying concentrations of L-lactate from 13 to 530 mM. The greatest differences between H4-type and M4-type isoenzymes in reaction rates were observed when their activities were compared in a reaction mixture containing 530 mM lactate and NAD, and also in a system of 13 mM lactate with thionicotinamide-hypoxanthine dinucleotide as a cofactor. The ratio of the LDH activity exerted in the former reaction mixture to that exerted in the latter was termed the N/T value. The N/T values of porcine H4 and M4 isoenzymes were 0.49 and 9.33, respectively. The N/T values of other three isoenzymes (H3M1, H2M2 and H1M3) were calculated by assuming that the single subunits H1 and M1 contribute one-fourth of the values of 0.49 and 9.33, respectively, and a given isoenzyme which is a combination of four subunits of H and M comprises the sum of their values. The calculated values agreed fairly well with the experimental results. The N/T value method was found to be applicable to human LDH isoenzymes, and sera from various patients were analyzed in comparison with hormonal sera. The method is particularly suitable for the numerical expression of LDH isoenzyme profiles."} {"id": "PMID:179739", "title": "Application of nicotin amide-adenine dinucleotide analogs for clinical enzymology: alcohol dehydrogenase activity in liver injury.", "content": "The activities of alcohol dehydrogease(ADH) in serum and in the subcellular fractions of rat liver were determined with n-amyl alcohol or ethanol as substrate and thionicotinamide-adenine dinucleotide as coenzyme. It was found that the enzyme's activity ratio on the amyl alcohol and ethanol(A/E value) of serum and on the particulate fractions of the liver were different, but the A/E value of the soluble fraction was similar to that of serum. The A/E value of the particulate fractions were higher than that of the soluble fraction. From the results of experimental liver damage in the rat, it seems that estimation of the A/E value of ADH activity in serum is a useful parameter for the diagnosis of active liver injury. Since the A/E values of patients' sera differed from those of the normal subjects, the estimation of the A/E value of serum may give diagnostic information on liver injury, especially in chronic liver injury.", "contents": "Application of nicotin amide-adenine dinucleotide analogs for clinical enzymology: alcohol dehydrogenase activity in liver injury. The activities of alcohol dehydrogease(ADH) in serum and in the subcellular fractions of rat liver were determined with n-amyl alcohol or ethanol as substrate and thionicotinamide-adenine dinucleotide as coenzyme. It was found that the enzyme's activity ratio on the amyl alcohol and ethanol(A/E value) of serum and on the particulate fractions of the liver were different, but the A/E value of the soluble fraction was similar to that of serum. The A/E value of the particulate fractions were higher than that of the soluble fraction. From the results of experimental liver damage in the rat, it seems that estimation of the A/E value of ADH activity in serum is a useful parameter for the diagnosis of active liver injury. Since the A/E values of patients' sera differed from those of the normal subjects, the estimation of the A/E value of serum may give diagnostic information on liver injury, especially in chronic liver injury."} {"id": "PMID:179740", "title": "The determination of silicates in urinary calculi.", "content": "The determination of silica and silicates in urinary calculi is rendered difficult by the common occurrence in such material of high concentrations of calcium, magnesium and orthophosphate. The problem has been studied, and manual and semi-automated procedures for the determination are described. 145 stones from the urinary tracts of patients with spinal cord injury were analysed, but in all of them the silicon content was below the limit of detection of 0.7 gSiO2 per 100 g calculus.", "contents": "The determination of silicates in urinary calculi. The determination of silica and silicates in urinary calculi is rendered difficult by the common occurrence in such material of high concentrations of calcium, magnesium and orthophosphate. The problem has been studied, and manual and semi-automated procedures for the determination are described. 145 stones from the urinary tracts of patients with spinal cord injury were analysed, but in all of them the silicon content was below the limit of detection of 0.7 gSiO2 per 100 g calculus."} {"id": "PMID:179741", "title": "Neonatal metabolism and endocrinology studied by exchange transfusion.", "content": "The work reviewed here illustrates how a therapeutic procedure, exchange transfusion of newborn infants, may be used to gather information which is both of practical value to infants treated in this way and also of value in the study of human neonatal physiology. The scientific deductions that can be drawn are weakened by the uncontrolled nature of the subjects available for study but this problem can be mitigated by changing one variable at a time between two groups of clinically similar infants undergoing transfusion and paying attention only to large changes in whatever is measured. In this way it has been possible to show that the glucose of ACD blood stimulates insulin and GH secretion and that the stimulation of insulin secretion is less, and that of GH more, if the transfusion is performed via the umbilical artery rather than via the vein. Arterial transfusions may be more stressful than venous ones since they are associated with greater growth hormone, ACTH and glucocorticoid release. Citrate, the other additive in ACD blood, causes a fall in ionised plasma calcium levels resulting in a stimulation of PTH secretion and mobilisation of calcium and phosphorus. Transfusion with heparinised blood is therefore preferred by some because normoglycaemia is preserved during and for three hours after transfusion, whereas post-transfusion hypoglycaemia may occur after ACD transfusion. However, heparin transfusion causes a marked rise in plasma FFA levels which may interfere with the binding of bilirubin by albumin. In either type of transfusion the side-effects may be minimised by feeding the baby afterwards, as soon as practicable. Thyroid hormones are washed out of the infant during transfusion but normal thyroid balance is restored quickly afterwards. The temperature of the donor blood does have thermal effects on the baby but these are less than might be expected due to the rapid equilibration of donor blood temperature with that of the room. The metabolic consequences of transfusion with cold blood are less than might be anticipated due in part to the glucose infusion that is part of an ACD transfusion.", "contents": "Neonatal metabolism and endocrinology studied by exchange transfusion. The work reviewed here illustrates how a therapeutic procedure, exchange transfusion of newborn infants, may be used to gather information which is both of practical value to infants treated in this way and also of value in the study of human neonatal physiology. The scientific deductions that can be drawn are weakened by the uncontrolled nature of the subjects available for study but this problem can be mitigated by changing one variable at a time between two groups of clinically similar infants undergoing transfusion and paying attention only to large changes in whatever is measured. In this way it has been possible to show that the glucose of ACD blood stimulates insulin and GH secretion and that the stimulation of insulin secretion is less, and that of GH more, if the transfusion is performed via the umbilical artery rather than via the vein. Arterial transfusions may be more stressful than venous ones since they are associated with greater growth hormone, ACTH and glucocorticoid release. Citrate, the other additive in ACD blood, causes a fall in ionised plasma calcium levels resulting in a stimulation of PTH secretion and mobilisation of calcium and phosphorus. Transfusion with heparinised blood is therefore preferred by some because normoglycaemia is preserved during and for three hours after transfusion, whereas post-transfusion hypoglycaemia may occur after ACD transfusion. However, heparin transfusion causes a marked rise in plasma FFA levels which may interfere with the binding of bilirubin by albumin. In either type of transfusion the side-effects may be minimised by feeding the baby afterwards, as soon as practicable. Thyroid hormones are washed out of the infant during transfusion but normal thyroid balance is restored quickly afterwards. The temperature of the donor blood does have thermal effects on the baby but these are less than might be expected due to the rapid equilibration of donor blood temperature with that of the room. The metabolic consequences of transfusion with cold blood are less than might be anticipated due in part to the glucose infusion that is part of an ACD transfusion."} {"id": "PMID:179742", "title": "Prenatal diagnosis of homoxygous familial hypercholesterolemia: investigation of a case at risk.", "content": "Cultivated amnion cells obtained from a pregnancy at risk for the homozygous form of familial hypercholesterolemia were analyzed, as were fibroblasts from normal, heterozygous and homozygous controls. Three different methods were employed in order to compare their diagnostic value: i. Acetate incorporation into the cellular 3beta-OH-sterol fraction; ii. LDL-binding to the cell surface receptor; and iii. Oleate incorporation into the cholesterylester pool of the cells after addition of LDL to lipoprotein-deficient growth medium. The best discrimination between normal, heterozygous and homozygous cells was achieved using the third technique. On the basis of the acetate incorporation analysis, we concluded that the child is not homozygous, but probably completely unaffected. This diagnosis was confirmed by repeated determinations of plasma cholesterol levels during the first 11 months of life. Our investigations further substantiate the specularion that prenatal diagnosis of this disorder is possible.", "contents": "Prenatal diagnosis of homoxygous familial hypercholesterolemia: investigation of a case at risk. Cultivated amnion cells obtained from a pregnancy at risk for the homozygous form of familial hypercholesterolemia were analyzed, as were fibroblasts from normal, heterozygous and homozygous controls. Three different methods were employed in order to compare their diagnostic value: i. Acetate incorporation into the cellular 3beta-OH-sterol fraction; ii. LDL-binding to the cell surface receptor; and iii. Oleate incorporation into the cholesterylester pool of the cells after addition of LDL to lipoprotein-deficient growth medium. The best discrimination between normal, heterozygous and homozygous cells was achieved using the third technique. On the basis of the acetate incorporation analysis, we concluded that the child is not homozygous, but probably completely unaffected. This diagnosis was confirmed by repeated determinations of plasma cholesterol levels during the first 11 months of life. Our investigations further substantiate the specularion that prenatal diagnosis of this disorder is possible."} {"id": "PMID:179743", "title": "Lp(a) lipoprotein/pre-beta1-lipoprotein, serum lipids and atherosclerotic disease.", "content": "With appropriate electrophoretic techniques and fresh serum samples, the Lp(a) lipoprotein/pre-beta1-lipoprotein is demonstrable as a distinct zone in the area between beta-lipoprotein and ordinary pre-beta-lipoprotein, when sera which are strongly positive with respect to the Lp(a) antigen are analyzed. The Lp(a) lipoprotein is a genetically determined normal serum component. The phenotype Lp(a+) was found significantly more frequently in two series of patients with coronary heart disease (CHD) than in appropriate controls. The frequency difference between patients and controls was particularly pronounced for the Finnish samples studied, 55% of the patients having the phenotype Lp(a+), as opposed to only 31% of the healthy controls. As judged from electrophoresis strips, hibh concentrations of Lp(a) lipoprotein/pre-beta1-lipoprotein were positively correlated with coronary score as determined by angiography. This correlation was highly significant. Total serum cholesterol value was slightly higher in Lp(a+) than in Lp(a-) persons from two of the four population samples studied, but no statistically significant difference was found. Serum triglyceride levels exhibited a statistically insignificant trend towards higher values in Lp(a-) than in Lp(a+) individuals, in three of the four samples tested. The strong association between the phenotype Lp(a+) and CHD, as well as the correlation between high amounts of Lp(a) lipoprotein/pre-beta1-lipoprotein and coronary score on one hand, and the weak correlation between presence of Lp(a) lipoprotein/pre-beta1-lipoprotein and lipid values on the other, make it highly unlikely that the increased frequency of the Lp(a+) phenotype in CHD patients merely reflects an over-all increase of the intravascular pool of LDL and/or VLDL reflected in increased serum levels of cholesterol and/or triglycerides. By the same token, it is unlikely that the insignificant effect on lipid values can, on its own, explain the correlation between Lp(a) phenotype and CHD.", "contents": "Lp(a) lipoprotein/pre-beta1-lipoprotein, serum lipids and atherosclerotic disease. With appropriate electrophoretic techniques and fresh serum samples, the Lp(a) lipoprotein/pre-beta1-lipoprotein is demonstrable as a distinct zone in the area between beta-lipoprotein and ordinary pre-beta-lipoprotein, when sera which are strongly positive with respect to the Lp(a) antigen are analyzed. The Lp(a) lipoprotein is a genetically determined normal serum component. The phenotype Lp(a+) was found significantly more frequently in two series of patients with coronary heart disease (CHD) than in appropriate controls. The frequency difference between patients and controls was particularly pronounced for the Finnish samples studied, 55% of the patients having the phenotype Lp(a+), as opposed to only 31% of the healthy controls. As judged from electrophoresis strips, hibh concentrations of Lp(a) lipoprotein/pre-beta1-lipoprotein were positively correlated with coronary score as determined by angiography. This correlation was highly significant. Total serum cholesterol value was slightly higher in Lp(a+) than in Lp(a-) persons from two of the four population samples studied, but no statistically significant difference was found. Serum triglyceride levels exhibited a statistically insignificant trend towards higher values in Lp(a-) than in Lp(a+) individuals, in three of the four samples tested. The strong association between the phenotype Lp(a+) and CHD, as well as the correlation between high amounts of Lp(a) lipoprotein/pre-beta1-lipoprotein and coronary score on one hand, and the weak correlation between presence of Lp(a) lipoprotein/pre-beta1-lipoprotein and lipid values on the other, make it highly unlikely that the increased frequency of the Lp(a+) phenotype in CHD patients merely reflects an over-all increase of the intravascular pool of LDL and/or VLDL reflected in increased serum levels of cholesterol and/or triglycerides. By the same token, it is unlikely that the insignificant effect on lipid values can, on its own, explain the correlation between Lp(a) phenotype and CHD."} {"id": "PMID:179747", "title": "Pulmonary metastases in Wilms' tumour.", "content": "In a series of 87 patients with a diagnosis of Wilms' tumour seen at the Great Ormond Street Hospital for Sick Children between 1960 and 1973, 15 patients had pulmonary metastases at the time of diagnosis and a further 22 patients developed pulmonary metastases within 18 months of their initial nephrectomy. The incidence of later development of metastases was very much greater in those patients with locally advanced primary tumours than in those with a completely resectable, encapsulated tumour. In both groups of patients the disease-free survival rate was closely related to initial local tumour staging. In the whole series there were 11/37 (42-5%) patients with pulmonary metastases who survived disease-free for two or more years following treatment. The survival rate was highest in those patients who had a solitary pulmonary metastasis which was surgically resected (5/6); this type of lesion was seen only in those patients who had a localised primary tumour. In those patients with multiple pulmonary metastases, treated with irradiation to the whole lungs and single-agent chemotherapy, there were only 6/31 disease-free survivors; this group of patients all had advanced primary tumours and there was a high incidence of associated abdominal recurrence. The need for multiple agent chemotherapy in conjunctin with surgery and radiotherapy, both as prophylaxis against and in the treatment of metastases from Wilms' tumour is stressed.", "contents": "Pulmonary metastases in Wilms' tumour. In a series of 87 patients with a diagnosis of Wilms' tumour seen at the Great Ormond Street Hospital for Sick Children between 1960 and 1973, 15 patients had pulmonary metastases at the time of diagnosis and a further 22 patients developed pulmonary metastases within 18 months of their initial nephrectomy. The incidence of later development of metastases was very much greater in those patients with locally advanced primary tumours than in those with a completely resectable, encapsulated tumour. In both groups of patients the disease-free survival rate was closely related to initial local tumour staging. In the whole series there were 11/37 (42-5%) patients with pulmonary metastases who survived disease-free for two or more years following treatment. The survival rate was highest in those patients who had a solitary pulmonary metastasis which was surgically resected (5/6); this type of lesion was seen only in those patients who had a localised primary tumour. In those patients with multiple pulmonary metastases, treated with irradiation to the whole lungs and single-agent chemotherapy, there were only 6/31 disease-free survivors; this group of patients all had advanced primary tumours and there was a high incidence of associated abdominal recurrence. The need for multiple agent chemotherapy in conjunctin with surgery and radiotherapy, both as prophylaxis against and in the treatment of metastases from Wilms' tumour is stressed."} {"id": "PMID:179748", "title": "Evaluation of gallium-67 in the diagnosis of bronchial carcinoma.", "content": "Twenty-four patients with carcinoma of the bronchus had lung scans performed with gallium-67. The results were compared with corresponding chest radiographs. In four patients who had been treated with radiotherapy or cytotoxic drugs, there was no uptake of isotope in the lesion. The isotope, however, identified the neoplasm accurately in 17 out of the 20 cases (85%). The relative distribution of isotope in neoplastic tissue and adjacent inflammatory reaction is discussed as well as those cases in which either the radiograph or the scan failed to demonstrate the malignant lesion. Gallium scanning in this study failed to indicate the extension of growth into the mediastinal glands.", "contents": "Evaluation of gallium-67 in the diagnosis of bronchial carcinoma. Twenty-four patients with carcinoma of the bronchus had lung scans performed with gallium-67. The results were compared with corresponding chest radiographs. In four patients who had been treated with radiotherapy or cytotoxic drugs, there was no uptake of isotope in the lesion. The isotope, however, identified the neoplasm accurately in 17 out of the 20 cases (85%). The relative distribution of isotope in neoplastic tissue and adjacent inflammatory reaction is discussed as well as those cases in which either the radiograph or the scan failed to demonstrate the malignant lesion. Gallium scanning in this study failed to indicate the extension of growth into the mediastinal glands."} {"id": "PMID:179749", "title": "The spectrophotometric determination of human serum carboxypolypeptidase with angiotensin converting enzyme-like activity.", "content": "1. A colorimetric method was developed for the direct chemical assay of human carboxypeptidase A (carboxypolypeptidase; EC 3.4.12.2) with angiotensin converting enzyme-like activity in serum or plasma, with the substrate analogue glycyl-L-histidylglycine and the angiotensin converting enzyme substrate angiotensin I (A-I). This method was based on the spectrophototometric determination of histidylglycine and histidyl-leucine, products of the hydrolysis of glycyl-L-histidylglycine and A-I respectively. omicron-Phthalaldehyde reacted with the imidazole moiety of nu-terminal histidyl peptides to produce a yellow chromophore. 2. A large number of inhibitors were tested for their effects on carboxypolpeptidase activity. The hydrolysis of Gly-His-Gly and A-I was inhibited by histidyl-leucine and angiotensin II, both products of the hydrolysis of A-I. Bothrops jararaca venom extract, EDTA, rho-chloromercuribenzoate, 8-hydroxyquinoline and 2,3-dimercaptopropanol, previously reported as converting enzyme inhibitors, also inhibited carboxypolypeptidase activity. 3. Angiotensin converting enzyme activity in the serum of sixty-six adults ranged from 10 to 37 nmol of glycyl-L-histidylglygine hydrolysed in 10 min by 10 mu1 of serum at 37 degrees C and pH 7-25.", "contents": "The spectrophotometric determination of human serum carboxypolypeptidase with angiotensin converting enzyme-like activity. 1. A colorimetric method was developed for the direct chemical assay of human carboxypeptidase A (carboxypolypeptidase; EC 3.4.12.2) with angiotensin converting enzyme-like activity in serum or plasma, with the substrate analogue glycyl-L-histidylglycine and the angiotensin converting enzyme substrate angiotensin I (A-I). This method was based on the spectrophototometric determination of histidylglycine and histidyl-leucine, products of the hydrolysis of glycyl-L-histidylglycine and A-I respectively. omicron-Phthalaldehyde reacted with the imidazole moiety of nu-terminal histidyl peptides to produce a yellow chromophore. 2. A large number of inhibitors were tested for their effects on carboxypolpeptidase activity. The hydrolysis of Gly-His-Gly and A-I was inhibited by histidyl-leucine and angiotensin II, both products of the hydrolysis of A-I. Bothrops jararaca venom extract, EDTA, rho-chloromercuribenzoate, 8-hydroxyquinoline and 2,3-dimercaptopropanol, previously reported as converting enzyme inhibitors, also inhibited carboxypolypeptidase activity. 3. Angiotensin converting enzyme activity in the serum of sixty-six adults ranged from 10 to 37 nmol of glycyl-L-histidylglygine hydrolysed in 10 min by 10 mu1 of serum at 37 degrees C and pH 7-25."} {"id": "PMID:179750", "title": "Effect of diphosphonates on adenosine 3':5'-cyclic monophosphate in mouse calvaria after stimulation by parathyroid hormone in vitro.", "content": "1. The diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP), inhibit bone resorption in animals and in explanted bone in tissue culture. The possibility that these effects might be due to inhibition of skeletal adenylate cyclase has been studied. 2. EHDP and Cl2MDP, added for 30 min to the incubation medium at concentrations known to inhibit bone resorption, had no effect on basal content of adenosine 3':5'-cyclic monophosphate (cyclic AMP) of mouse calvaria incubated in vitro, nor did they inhibit the rise in cyclic AMP induced by bovine parathyroid hormone. 3. Pretreatment of mice for 3 days with Cl2MDP also had no effect on cyclic AMP under basal conditions or after incubation of explanted calvaria with parathyroid hormone in vitro. EHDP under similar conditions slightly inhibited the increase induced by parathyroid hormone but had no effect on basal concentrations of cyclic AMP. 4. It is suggested that the inhibition of adenylate cyclase is not an essential feature of the reduction of bone resorption by diphosphonates, which may act by direct inhibitory effects on the dissolution of hydroxyapatite and perhaps by other unidentified effects on bone cells. Key words: adenosine 3':5'-cyclic monophosphate, bone, dichloromethylene diphosphonate, diphosphonates, ethane-1-hydroxy-1,1-diphosphonate, parathyroid hormone.", "contents": "Effect of diphosphonates on adenosine 3':5'-cyclic monophosphate in mouse calvaria after stimulation by parathyroid hormone in vitro. 1. The diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP), inhibit bone resorption in animals and in explanted bone in tissue culture. The possibility that these effects might be due to inhibition of skeletal adenylate cyclase has been studied. 2. EHDP and Cl2MDP, added for 30 min to the incubation medium at concentrations known to inhibit bone resorption, had no effect on basal content of adenosine 3':5'-cyclic monophosphate (cyclic AMP) of mouse calvaria incubated in vitro, nor did they inhibit the rise in cyclic AMP induced by bovine parathyroid hormone. 3. Pretreatment of mice for 3 days with Cl2MDP also had no effect on cyclic AMP under basal conditions or after incubation of explanted calvaria with parathyroid hormone in vitro. EHDP under similar conditions slightly inhibited the increase induced by parathyroid hormone but had no effect on basal concentrations of cyclic AMP. 4. It is suggested that the inhibition of adenylate cyclase is not an essential feature of the reduction of bone resorption by diphosphonates, which may act by direct inhibitory effects on the dissolution of hydroxyapatite and perhaps by other unidentified effects on bone cells. Key words: adenosine 3':5'-cyclic monophosphate, bone, dichloromethylene diphosphonate, diphosphonates, ethane-1-hydroxy-1,1-diphosphonate, parathyroid hormone."} {"id": "PMID:179751", "title": "The effect of insulin on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate concentrations in human plasma.", "content": "1. The action of insulin on plasma cyclic nucleotide concentrations in normal human subjects has been studied after intravenous injection, alone and in combination with glucagon. 2. After injection of insulin alone there was an initial small, though not significant, decrease in plasma cyclic AMP at 15 min followed by an increase to more than twice the initial concentration at 30 min. The increase was absent when hypoglycaemia was lessened by infusion of glucose after insulin injection. 3. Injection of insulin caused no significant change in plasma cyclic GMP concentration, whether or not glucose was infused after the hormone. 4. Glucagon (3-300 nmol, 10-1000 mug), caused a dose-dependent increase in plasma cyclic AMP concentration. The rise in plasma cyclic AMP produced by 3 or 30 nmol of glucagon was not significantly modified by simultaneous injection of insulin (44 nmol; 6 units).", "contents": "The effect of insulin on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate concentrations in human plasma. 1. The action of insulin on plasma cyclic nucleotide concentrations in normal human subjects has been studied after intravenous injection, alone and in combination with glucagon. 2. After injection of insulin alone there was an initial small, though not significant, decrease in plasma cyclic AMP at 15 min followed by an increase to more than twice the initial concentration at 30 min. The increase was absent when hypoglycaemia was lessened by infusion of glucose after insulin injection. 3. Injection of insulin caused no significant change in plasma cyclic GMP concentration, whether or not glucose was infused after the hormone. 4. Glucagon (3-300 nmol, 10-1000 mug), caused a dose-dependent increase in plasma cyclic AMP concentration. The rise in plasma cyclic AMP produced by 3 or 30 nmol of glucagon was not significantly modified by simultaneous injection of insulin (44 nmol; 6 units)."} {"id": "PMID:179752", "title": "Effects of prednisolone on the small intestinal mucosa of the rat.", "content": "1. The effects in rats of an oral pharmacological dose of prednisolone on mucosal function, enzymology, lysosomal membrane fragility, morphology and cell kinetics have been examined in proximal jejunum and distal ileum. 2. The maximum absorptive capacity for galactose was significantly greater in both the jejunum and the ileum of the steroid-treated animals. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. The Michaelis constant for galactose was not significantly altered by prednisolone. 3. Activities of brush-border and mitochondrial enzymes and of RNA were increased in isolated enterocyte preparations from the jejunum and ileum of the steroid-treated group. 4. Lysosomal membrane fragility was unaltered in the prednisolone-treated group. 5. Morphometrical observations confirmed that the size of the enterocyte population was unaltered by prednisolone. Studies on cell kinetics indicate that the effects of prednisolone are due to a direct action on the enterocyte and not secondary to changes in migration rate.", "contents": "Effects of prednisolone on the small intestinal mucosa of the rat. 1. The effects in rats of an oral pharmacological dose of prednisolone on mucosal function, enzymology, lysosomal membrane fragility, morphology and cell kinetics have been examined in proximal jejunum and distal ileum. 2. The maximum absorptive capacity for galactose was significantly greater in both the jejunum and the ileum of the steroid-treated animals. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. The Michaelis constant for galactose was not significantly altered by prednisolone. 3. Activities of brush-border and mitochondrial enzymes and of RNA were increased in isolated enterocyte preparations from the jejunum and ileum of the steroid-treated group. 4. Lysosomal membrane fragility was unaltered in the prednisolone-treated group. 5. Morphometrical observations confirmed that the size of the enterocyte population was unaltered by prednisolone. Studies on cell kinetics indicate that the effects of prednisolone are due to a direct action on the enterocyte and not secondary to changes in migration rate."} {"id": "PMID:179753", "title": "Diseases associated with herpesviruses.", "content": "Human herpesviruses have been associated with numerous diseases throughout history (Table 3), but their ability to induce latent and recurrent infections, alongwith their oncogenic capabilities, is only beginning to be understood. Accordingly, our ability to deal with the diseases induced by herpesviruses is severely limited by our lack of information concerning the basic processes of virus-host cell interactions and systemic host factors; especially immune factors that are involved in the disease process.", "contents": "Diseases associated with herpesviruses. Human herpesviruses have been associated with numerous diseases throughout history (Table 3), but their ability to induce latent and recurrent infections, alongwith their oncogenic capabilities, is only beginning to be understood. Accordingly, our ability to deal with the diseases induced by herpesviruses is severely limited by our lack of information concerning the basic processes of virus-host cell interactions and systemic host factors; especially immune factors that are involved in the disease process."} {"id": "PMID:179759", "title": "The abnormal brain scan: specificity of descriptive parameters.", "content": "When a brain scan is abnormal, one can often describe the abnormality in terms of its location, shape, sharpness, brightness, and other descriptive parameters. Certain types of abnormality have been linked to certain specific diagnoses: for example, a crescent-shaped lesion would suggest subdural hematoma to many people, a wedge-shaped lesion would suggest cerebral vascular accident, etc. Some features thought to be characteristic of certain diseases are actually quite nonspecific. For example, the \"doughnut\" sign--at first believed to be characteristic of brain abscess--has also been found in primary and metastatic tumors, CVA, and subdural hematoma. The \"crescent\" sign that was at first thought to be specific for subdural hematoma occurs also in meningitis, scalp or skull trauma, meningioma en plaque, etc. Some features of abnormalities are highly specific for certain diseases; e.g., wedge- or flame-shaped lesions are rarely seen with disorders other than CVA, and lesions in the midline or in the posterior fossa are almost invariably tumors. This article reviews the features of abnormalities on brain scans that in the literature have been reportedly associated with specific types of disease and explores the strength and validity of the associations.", "contents": "The abnormal brain scan: specificity of descriptive parameters. When a brain scan is abnormal, one can often describe the abnormality in terms of its location, shape, sharpness, brightness, and other descriptive parameters. Certain types of abnormality have been linked to certain specific diagnoses: for example, a crescent-shaped lesion would suggest subdural hematoma to many people, a wedge-shaped lesion would suggest cerebral vascular accident, etc. Some features thought to be characteristic of certain diseases are actually quite nonspecific. For example, the \"doughnut\" sign--at first believed to be characteristic of brain abscess--has also been found in primary and metastatic tumors, CVA, and subdural hematoma. The \"crescent\" sign that was at first thought to be specific for subdural hematoma occurs also in meningitis, scalp or skull trauma, meningioma en plaque, etc. Some features of abnormalities are highly specific for certain diseases; e.g., wedge- or flame-shaped lesions are rarely seen with disorders other than CVA, and lesions in the midline or in the posterior fossa are almost invariably tumors. This article reviews the features of abnormalities on brain scans that in the literature have been reportedly associated with specific types of disease and explores the strength and validity of the associations."} {"id": "PMID:179763", "title": "Poly-hormonal evaluationof pulsatile adenohypophysis incretory activity during sleep in normal, experimental and pathologic conditions.", "content": "Secretory patterns of some anterior pituitary hormones were recorded during sleep, and related to EEG-phases. The same observations were carried out in conditions in which the normal sleep course was intentionall (i.e., repeated arousals, administration of tryptophan) or pathologically (i.e. chronic schizophrenia) modified. Plasma gonadotropins (lh, fsh), growth hormone and ACTH were assayed. In basal conditions, the well-known peak of HGH, which corresponds to the delta phase of sleep, was confirmed. This peak is strictly linked to the number and duration of stage 4 sleep, and follows it in its experimental and/or pathological disturbances. The secretion of ACTH, on the other hand, seems to be completely independent from the morphology of sleep. The secretion of this hormone is typically phasic; along with this phasic secretion, a background secretion is detectable, which increases steadily during the sleep span, with maximal values in the early morning hours. Gonadotropin secretion is pulsatile, episodic and completely independent from the sleep phases, in basal as well as in experimental and pathologic conditions.", "contents": "Poly-hormonal evaluationof pulsatile adenohypophysis incretory activity during sleep in normal, experimental and pathologic conditions. Secretory patterns of some anterior pituitary hormones were recorded during sleep, and related to EEG-phases. The same observations were carried out in conditions in which the normal sleep course was intentionall (i.e., repeated arousals, administration of tryptophan) or pathologically (i.e. chronic schizophrenia) modified. Plasma gonadotropins (lh, fsh), growth hormone and ACTH were assayed. In basal conditions, the well-known peak of HGH, which corresponds to the delta phase of sleep, was confirmed. This peak is strictly linked to the number and duration of stage 4 sleep, and follows it in its experimental and/or pathological disturbances. The secretion of ACTH, on the other hand, seems to be completely independent from the morphology of sleep. The secretion of this hormone is typically phasic; along with this phasic secretion, a background secretion is detectable, which increases steadily during the sleep span, with maximal values in the early morning hours. Gonadotropin secretion is pulsatile, episodic and completely independent from the sleep phases, in basal as well as in experimental and pathologic conditions."} {"id": "PMID:179764", "title": "Circadian rhythm and cell cycle: possible entraining mechanisms.", "content": "Circadian rhythms and cell cycles are endogenous self-sustained oscillations. They differ in several characteristics of the rhythmicity such as temperature dependency, reaction to external stimuli and the impact of protein synthesis. In multicellular organisms, the cell cycle very often is entrained by a circadian rhythm as has been analyzed in rats and mice, in particular. The same seems to hold true in cell cultures: Yoshida-ascites hepatoma cells, human embryonic fibroblasts, rat liver and rat hepatoma cells show circadian changes in the percentage of cells in G1-, S- and G2 + M-phases. The different phases within the cell cycle were determined by applying impulse cytophotometric methods. Some hypothetical mechanisms of entrainment of the cell cycle by circadian rhythms are discussed. Possible entrancing signals (Zeitgebers) are membrane and transport functions, cyclic nucleotides, nuclear non-histone proteins and their phosphorylation, and RNA synthesis. The maxima of the circadian rhythms of most of these functions in rat liver can be arranged in a certain temporal sequence.", "contents": "Circadian rhythm and cell cycle: possible entraining mechanisms. Circadian rhythms and cell cycles are endogenous self-sustained oscillations. They differ in several characteristics of the rhythmicity such as temperature dependency, reaction to external stimuli and the impact of protein synthesis. In multicellular organisms, the cell cycle very often is entrained by a circadian rhythm as has been analyzed in rats and mice, in particular. The same seems to hold true in cell cultures: Yoshida-ascites hepatoma cells, human embryonic fibroblasts, rat liver and rat hepatoma cells show circadian changes in the percentage of cells in G1-, S- and G2 + M-phases. The different phases within the cell cycle were determined by applying impulse cytophotometric methods. Some hypothetical mechanisms of entrainment of the cell cycle by circadian rhythms are discussed. Possible entrancing signals (Zeitgebers) are membrane and transport functions, cyclic nucleotides, nuclear non-histone proteins and their phosphorylation, and RNA synthesis. The maxima of the circadian rhythms of most of these functions in rat liver can be arranged in a certain temporal sequence."} {"id": "PMID:179772", "title": "[VIP and GIP-producing pancreatic tumour: relationship to the Verner-Morrison syndrome].", "content": "A 59-year-old man had explosive watery diarrhoea, tendency towards collapse, flushes and aphonia. Pre-operative serum concentrations of vasoactive intestinal polypeptide (VIP) were up to 1030 ng/l, those of gastric inhibitory polypeptide (GIP) up to 2675 ng/l, as measured by radioimmunoassay. Cross-reaction by antisera used in the radioimmunoassay were excluded. Pancreatic tumour was diagnosed by ultrasound and by elective coeliac arteriography. After excision the abnormal fidings disappeared as did the symptoms. Biological half-life of plasma-VIP (determined during removal of the tumour from plasma samples by radioimmunoassay) was about 45 minutes. The tumour produced both VIP and GIP.", "contents": "[VIP and GIP-producing pancreatic tumour: relationship to the Verner-Morrison syndrome]. A 59-year-old man had explosive watery diarrhoea, tendency towards collapse, flushes and aphonia. Pre-operative serum concentrations of vasoactive intestinal polypeptide (VIP) were up to 1030 ng/l, those of gastric inhibitory polypeptide (GIP) up to 2675 ng/l, as measured by radioimmunoassay. Cross-reaction by antisera used in the radioimmunoassay were excluded. Pancreatic tumour was diagnosed by ultrasound and by elective coeliac arteriography. After excision the abnormal fidings disappeared as did the symptoms. Biological half-life of plasma-VIP (determined during removal of the tumour from plasma samples by radioimmunoassay) was about 45 minutes. The tumour produced both VIP and GIP."} {"id": "PMID:179773", "title": "[Late effects of tumour treatment. Structural changes in the spinal column seen on X-rays].", "content": "Cure rates are increasing in pediatric oncology; simultaneously the numbers of late effects of therapy are also increasing. 64 children with malignant neoplastic disease in whom the spine had been partially or totally exposed during X-ray treatment were re-investigated for radiographically visible irradiation effects on the vertebral column. 140 different abnormalties were found in 56 children of which scolioses were the most important. Irradiation for Wilms' tumour produced more numerous changes than direct irradiation of the vertebral column. In spite of the unexpectedly high number of growth defects rigorous X-ray treatment is indicated in certain circumstances. The growth abnormalities were of only minor clinical significance.", "contents": "[Late effects of tumour treatment. Structural changes in the spinal column seen on X-rays]. Cure rates are increasing in pediatric oncology; simultaneously the numbers of late effects of therapy are also increasing. 64 children with malignant neoplastic disease in whom the spine had been partially or totally exposed during X-ray treatment were re-investigated for radiographically visible irradiation effects on the vertebral column. 140 different abnormalties were found in 56 children of which scolioses were the most important. Irradiation for Wilms' tumour produced more numerous changes than direct irradiation of the vertebral column. In spite of the unexpectedly high number of growth defects rigorous X-ray treatment is indicated in certain circumstances. The growth abnormalities were of only minor clinical significance."} {"id": "PMID:179775", "title": "[Dynamics of sleep and the waking state after labyrinthine deafferentation].", "content": "The author carried out studies on Awake state and sleep (slow and paradoxal) after lybyrinth deafferentation. The states were evaluated by behavior, EEG, myogram and eye movements. The labyrinth defferentation was performed in combination (chemical and mechanical). Bilateral labyrinth deafferentation reduced the duration of the awake state from 30% to 17%, p less than 0.001. The slow sleep was increased at the same time but there was no statistical significance. The parodoxal sleep was due both to the increased number of episodes of parodoxal sleep and to the increased of their mean duration. The latent period of the first appearance of the episode of paradoxay sleep was shortened.", "contents": "[Dynamics of sleep and the waking state after labyrinthine deafferentation]. The author carried out studies on Awake state and sleep (slow and paradoxal) after lybyrinth deafferentation. The states were evaluated by behavior, EEG, myogram and eye movements. The labyrinth defferentation was performed in combination (chemical and mechanical). Bilateral labyrinth deafferentation reduced the duration of the awake state from 30% to 17%, p less than 0.001. The slow sleep was increased at the same time but there was no statistical significance. The parodoxal sleep was due both to the increased number of episodes of parodoxal sleep and to the increased of their mean duration. The latent period of the first appearance of the episode of paradoxay sleep was shortened."} {"id": "PMID:179776", "title": "[Mechanism of action of lithium in manic-depressive psychoses: current research results].", "content": "The mechanism of action lithium in the treatment of manic-depressive illness is far from being known. A great progress will be achieved when it is known wherther lithium has an actual anti-depressive action, which implies to determine whether all the \"endogenous\" depressive states belong to the same pathogenic group. Lithium salts have a real therapeutic action on manic states which may be put together with the decrease of available Norepinephrine that lithium salts bring about on cerebral receptors. This decrease concords with the aminergic theory of affective disorders. Many actions of lithium salts on the physiologic systems have been brought to evidence but the uncertainties that remain concerning their interactions prevent us to formulate any coherent assumption.", "contents": "[Mechanism of action of lithium in manic-depressive psychoses: current research results]. The mechanism of action lithium in the treatment of manic-depressive illness is far from being known. A great progress will be achieved when it is known wherther lithium has an actual anti-depressive action, which implies to determine whether all the \"endogenous\" depressive states belong to the same pathogenic group. Lithium salts have a real therapeutic action on manic states which may be put together with the decrease of available Norepinephrine that lithium salts bring about on cerebral receptors. This decrease concords with the aminergic theory of affective disorders. Many actions of lithium salts on the physiologic systems have been brought to evidence but the uncertainties that remain concerning their interactions prevent us to formulate any coherent assumption."} {"id": "PMID:179777", "title": "Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor.", "content": "We have consistently found receptors for estradiol in both the cytosol and nuclear extracts of a rat endometrial cell line and in transplantable tumors derived from this cell line. The equilibrium dissociation constants (Kd) and the rate constants for the receptor-estradiol interaction in these cells and tumors did not differ significantly from those of the cytosol receptor in the rat uterus. A mean Kd of 3 x 10(-10) M with a rate of association (Ka) of 3 x 10(5) M-1sec-1 and a rate of dissociation (Kd) of 1.5 x 10(-5) sec-1 were obtained for nuclear and cytosol receptors for both tumors and cells. For uterine cytosol, a Kd of 8 x 10(-10) M, ka = 2.8 x 10(5) M-1sec-1 and kd = 1 x 10(-5) sec-1 were obtained. Although no differences were seen in equilibrium and kinetic parameters for estradiol-17beta binding between the nuclear and cytosol receptors of tumors and cells, an apparent difference in the relative affinities of nuclear and cytosol receptors for estrone was detected. This suggests that the binding site in nuclear receptors may have been modified. Implications of this observation with regard to receptor translocation and the mechanism of action of sex hormones are being considered.", "contents": "Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor. We have consistently found receptors for estradiol in both the cytosol and nuclear extracts of a rat endometrial cell line and in transplantable tumors derived from this cell line. The equilibrium dissociation constants (Kd) and the rate constants for the receptor-estradiol interaction in these cells and tumors did not differ significantly from those of the cytosol receptor in the rat uterus. A mean Kd of 3 x 10(-10) M with a rate of association (Ka) of 3 x 10(5) M-1sec-1 and a rate of dissociation (Kd) of 1.5 x 10(-5) sec-1 were obtained for nuclear and cytosol receptors for both tumors and cells. For uterine cytosol, a Kd of 8 x 10(-10) M, ka = 2.8 x 10(5) M-1sec-1 and kd = 1 x 10(-5) sec-1 were obtained. Although no differences were seen in equilibrium and kinetic parameters for estradiol-17beta binding between the nuclear and cytosol receptors of tumors and cells, an apparent difference in the relative affinities of nuclear and cytosol receptors for estrone was detected. This suggests that the binding site in nuclear receptors may have been modified. Implications of this observation with regard to receptor translocation and the mechanism of action of sex hormones are being considered."} {"id": "PMID:179778", "title": "125I-LH binding to rat testes at various ages and posthypophysectomy.", "content": "Binding of 125I-LH by the rat testes was investigated during various stages of sexual maturation and in mature animals following hypophysectomy. Hormone binding per mg testicular tissue increased with age and was shown to be due to larger receptor concentration rather than greater binding affinity. This observation cannot be accounted for by changes in the relative number of Leydig cells and suggests, therefore, that Leydig cells acquire additional receptors during sexual maturation. Binding of 125I-LH to mature testes declined after hypophysectomy. Three days following pituitary removal the LH-receptor concentration decreased to one half of normal control value, then remained unchanged until the 37th post-operation day. Replacement therapy with LH, FSH or testosterone propionate failed to maintain 125I-LH binding at prehypophysectomy level.", "contents": "125I-LH binding to rat testes at various ages and posthypophysectomy. Binding of 125I-LH by the rat testes was investigated during various stages of sexual maturation and in mature animals following hypophysectomy. Hormone binding per mg testicular tissue increased with age and was shown to be due to larger receptor concentration rather than greater binding affinity. This observation cannot be accounted for by changes in the relative number of Leydig cells and suggests, therefore, that Leydig cells acquire additional receptors during sexual maturation. Binding of 125I-LH to mature testes declined after hypophysectomy. Three days following pituitary removal the LH-receptor concentration decreased to one half of normal control value, then remained unchanged until the 37th post-operation day. Replacement therapy with LH, FSH or testosterone propionate failed to maintain 125I-LH binding at prehypophysectomy level."} {"id": "PMID:179779", "title": "Elevation of cyclic AMP levels and adenylate cyclase activity in duodenal mucosa from vitamin D-deficient rats by 1alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3).", "content": "A single 270 ng dose of 1alpha,25-(OH2D3 rpoduced elevations in cyclic AMP content and adenylate cyclase activity in duodenal mucosa from previously vitamin D-deficient rats. No changes in jejunal or ileal cyclic AMP levels or duodenal cyclic GMP levels were observed. Since 1alpha,25-(OH)2D3 increased both baseline and NaF-stimulated adenylate cyclase activity, it is possible that the vitamin leads to enhanced enzyme synthesis. While parallel changes in duodenal cyclic AMP levels and active calcium absorption in response to 1alpha,25-(OH)2D3 were observed at 6,12,24 and 48 hr after treatment, increases in calcium absorption were observed at 3 hr in duodenum and at 48 hr in ileum in the absence of changes in cyclic AMP levels. Further studies will be required to determine whether or not the changes in duodenal cyclic AMP levels are direct or indirect effects of 1alpha,25-(OH)2D3 administration, and to determine the role, if any, of this nucleotide in the hormones' effect on intestinal calcium absorption.", "contents": "Elevation of cyclic AMP levels and adenylate cyclase activity in duodenal mucosa from vitamin D-deficient rats by 1alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3). A single 270 ng dose of 1alpha,25-(OH2D3 rpoduced elevations in cyclic AMP content and adenylate cyclase activity in duodenal mucosa from previously vitamin D-deficient rats. No changes in jejunal or ileal cyclic AMP levels or duodenal cyclic GMP levels were observed. Since 1alpha,25-(OH)2D3 increased both baseline and NaF-stimulated adenylate cyclase activity, it is possible that the vitamin leads to enhanced enzyme synthesis. While parallel changes in duodenal cyclic AMP levels and active calcium absorption in response to 1alpha,25-(OH)2D3 were observed at 6,12,24 and 48 hr after treatment, increases in calcium absorption were observed at 3 hr in duodenum and at 48 hr in ileum in the absence of changes in cyclic AMP levels. Further studies will be required to determine whether or not the changes in duodenal cyclic AMP levels are direct or indirect effects of 1alpha,25-(OH)2D3 administration, and to determine the role, if any, of this nucleotide in the hormones' effect on intestinal calcium absorption."} {"id": "PMID:179780", "title": "Binding of 125I-HCG by rat testis homogenates in early neonatal period.", "content": "The binding of 125I-HCG by rat testis homogenates in early neonatal period was studied. The specificity of this binding was demonstrated by competition of unlabeled HCG and LH for binding sites and by failure of such binding to occur in specimens obtained from control tissues. FSH and ACTH were not able to compete significantly for 125I-HCG binding. The HCG-LH receptor is present in the testis during the whole postnatal period. The uptake of 125I-HCG by the testis of young rat does not differ during first two weeks of life and the rise of binding occurs at about the third postnatal week.", "contents": "Binding of 125I-HCG by rat testis homogenates in early neonatal period. The binding of 125I-HCG by rat testis homogenates in early neonatal period was studied. The specificity of this binding was demonstrated by competition of unlabeled HCG and LH for binding sites and by failure of such binding to occur in specimens obtained from control tissues. FSH and ACTH were not able to compete significantly for 125I-HCG binding. The HCG-LH receptor is present in the testis during the whole postnatal period. The uptake of 125I-HCG by the testis of young rat does not differ during first two weeks of life and the rise of binding occurs at about the third postnatal week."} {"id": "PMID:179781", "title": "Binding of testosterone, dihydrotestosterone and progesterone to rat prostate cytosol: application of microcalorimetry.", "content": "The binding capacity of rat prostate cytosol for dihydrotestosterone, testosterone and progesterone was studied in vitro. The thermodynamic parameters obtained by microcalorimetry point to the importance of the observation of energy changes occuring during the hormone-receptor complex formation.", "contents": "Binding of testosterone, dihydrotestosterone and progesterone to rat prostate cytosol: application of microcalorimetry. The binding capacity of rat prostate cytosol for dihydrotestosterone, testosterone and progesterone was studied in vitro. The thermodynamic parameters obtained by microcalorimetry point to the importance of the observation of energy changes occuring during the hormone-receptor complex formation."} {"id": "PMID:179782", "title": "Radioligand- receptor assay of LH-RH.", "content": "Characteristics of LH-RH interactions with the plasma membrane of the anterior pituitary were utilized to develop a radioligand- receptor assay for the hypothalamic decapeptide. Plasma membranes were prepared from rat adenohypophyses and association of 125I-LH-RH with the cell membrane was found to reach a plateau after 30 min incubation time. Sensitivity of the present competitive protein binding assay was 10 ng. The system was shown to be sensitive to structural changes in the LH-RH molecule. No cross-reactivity of (3--10) LH-RH, pyro-His-Trp-SerOMe and TRH was recorded with LH-RH, whereas slight cross-reaction was observed for (Lys8) LH-RH and (Ala4) LH-RH showed marked cross-reaction. Although the present system is not sensitive enough to estimate physiological levels of LH-RH it seems to be a valuable approach for setting up an LH-RH assay system.", "contents": "Radioligand- receptor assay of LH-RH. Characteristics of LH-RH interactions with the plasma membrane of the anterior pituitary were utilized to develop a radioligand- receptor assay for the hypothalamic decapeptide. Plasma membranes were prepared from rat adenohypophyses and association of 125I-LH-RH with the cell membrane was found to reach a plateau after 30 min incubation time. Sensitivity of the present competitive protein binding assay was 10 ng. The system was shown to be sensitive to structural changes in the LH-RH molecule. No cross-reactivity of (3--10) LH-RH, pyro-His-Trp-SerOMe and TRH was recorded with LH-RH, whereas slight cross-reaction was observed for (Lys8) LH-RH and (Ala4) LH-RH showed marked cross-reaction. Although the present system is not sensitive enough to estimate physiological levels of LH-RH it seems to be a valuable approach for setting up an LH-RH assay system."} {"id": "PMID:179783", "title": "LH-RH-sensitive adenylate cyclase in isolated plasma membranes of rat adenohypophyses.", "content": "The adenylate cyclase system in isolated plasma membranes of rat adenohypophyses was studied. Formation of cAMP was found to be dependent on plasma membrane protein. Production of cAMP could be stimulated by the addition of LH-RH. This process was shown to be a function of LH-RH concentration. Basal and stimulated cAMP could be stimulated by NaF. The results of the present experiments suggest that cAMP formation is time dependent. The synthesis of cAMP is a possible effector of LH-RH actions.", "contents": "LH-RH-sensitive adenylate cyclase in isolated plasma membranes of rat adenohypophyses. The adenylate cyclase system in isolated plasma membranes of rat adenohypophyses was studied. Formation of cAMP was found to be dependent on plasma membrane protein. Production of cAMP could be stimulated by the addition of LH-RH. This process was shown to be a function of LH-RH concentration. Basal and stimulated cAMP could be stimulated by NaF. The results of the present experiments suggest that cAMP formation is time dependent. The synthesis of cAMP is a possible effector of LH-RH actions."} {"id": "PMID:179784", "title": "Milk-ejecting and uterotonic activities of oxytocin analogues in rats.", "content": "The milk-ejecting activity of oxytocin analogues modified in the aminoterminal part of the molecule was determined in experiment on rats in vivo. As compared with oxytocin, the analogues did not have significantly higher milk-ejecting activity and there was no dissociation of the two basic oxytocin-like activities.", "contents": "Milk-ejecting and uterotonic activities of oxytocin analogues in rats. The milk-ejecting activity of oxytocin analogues modified in the aminoterminal part of the molecule was determined in experiment on rats in vivo. As compared with oxytocin, the analogues did not have significantly higher milk-ejecting activity and there was no dissociation of the two basic oxytocin-like activities."} {"id": "PMID:179785", "title": "Effect of prolactin on LH receptor in rat luteal cells.", "content": "This investigation was undertaken to determine whether prolactin might act as a luteotropic hormone in the rat by increasing the receptor for LH. Immature female rats were treated with 5 SC injections of oFSH beginning at 0900 h on day 25; luteinization was induced with a single SC injection of oLH at 1500 h on day 27. In this model, LH-receptor activity, assessed by specific binding of [125I]iodohCG to ovarian membrane fractions, increased steadily (greater than 7-fold) from day 27 to day 33; specific [125I]iodoprolactin binding rose greater than 3-fold between days 27 and 31. Serum progesterone measured at 1500 h rose from greater than 10 ng/ml on day 27 to greater than 130 ng/ml on day 34. 2-Bromo-alpha-ergocryptine (CB-154, [EC]; 35 mug) given 2 X/day beginning at the time of LH injection, blocked nocturnal increases in serum prolactin measured at 0200 h on days 29, 30, and 31, and resulted in reduced binding of [125I]iodohCG on days 31 and 33; serum progesterone was similarly reduced on days 31 and 34 in EC-treated rats. Simultaneous treatment with EC and prolactin completely reversed the effects of EC with regard to both binding of [125A]iodohCG and serum progesterone. Changes in ovarian uptake of [125I]iodohCG in vivo were similar to those of the in vitro experiments described above. EC and/or prolactin treatment did not affect binding of [125I]iodoprolactin. In summary, the data indicate that LH in the absence of prolactin can induce the formation of corpora lutea which have an increased number of prolactin receptors but which have a few LH receptors and a reduced capacity to produce progesterone. If prolactin is present during the early luteinization process, corpora lutea develop an increased capacity to bind LH and to produce progesterone. It is possible that the increase in LH-receptor and progesterone production occur as independent events both mediated by the luteotropic action of prolactin. Alternatively, LH receptor might be limiting for LH stimulation of progesterone production.", "contents": "Effect of prolactin on LH receptor in rat luteal cells. This investigation was undertaken to determine whether prolactin might act as a luteotropic hormone in the rat by increasing the receptor for LH. Immature female rats were treated with 5 SC injections of oFSH beginning at 0900 h on day 25; luteinization was induced with a single SC injection of oLH at 1500 h on day 27. In this model, LH-receptor activity, assessed by specific binding of [125I]iodohCG to ovarian membrane fractions, increased steadily (greater than 7-fold) from day 27 to day 33; specific [125I]iodoprolactin binding rose greater than 3-fold between days 27 and 31. Serum progesterone measured at 1500 h rose from greater than 10 ng/ml on day 27 to greater than 130 ng/ml on day 34. 2-Bromo-alpha-ergocryptine (CB-154, [EC]; 35 mug) given 2 X/day beginning at the time of LH injection, blocked nocturnal increases in serum prolactin measured at 0200 h on days 29, 30, and 31, and resulted in reduced binding of [125I]iodohCG on days 31 and 33; serum progesterone was similarly reduced on days 31 and 34 in EC-treated rats. Simultaneous treatment with EC and prolactin completely reversed the effects of EC with regard to both binding of [125A]iodohCG and serum progesterone. Changes in ovarian uptake of [125I]iodohCG in vivo were similar to those of the in vitro experiments described above. EC and/or prolactin treatment did not affect binding of [125I]iodoprolactin. In summary, the data indicate that LH in the absence of prolactin can induce the formation of corpora lutea which have an increased number of prolactin receptors but which have a few LH receptors and a reduced capacity to produce progesterone. If prolactin is present during the early luteinization process, corpora lutea develop an increased capacity to bind LH and to produce progesterone. It is possible that the increase in LH-receptor and progesterone production occur as independent events both mediated by the luteotropic action of prolactin. Alternatively, LH receptor might be limiting for LH stimulation of progesterone production."} {"id": "PMID:179786", "title": "Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon \"resistance\".", "content": "Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon \"resistance\" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development.", "contents": "Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon \"resistance\". Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon \"resistance\" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development."} {"id": "PMID:179787", "title": "Sex-related differences in the regulation of cytoplasmic estrogen receptor levels in responsive tissues of the rat.", "content": "Cytoplasmic estrogen receptors were measured in the anterior pituitary and hypothalamus of intact adult Holtzman male and female rats at various time intervals following injection of 10 mug of 17beta-estradiol. Following equivalent depletion of receptors at 1 h in either sex, replenishment of cytosol receptor levels progressed at a greater rate and to a higher level in the male than in the female. Cycloheximide only partially inhibited replenishment, and its blocking effect was similar in males and females. The administration of 5 mug of 17beta-estradiol to adult males elicited less depletion than did 10 mug, and a completely cycloheximide-sensitive replenishment phase. Patterns of depletion and replenishment in immature rats following 0.1 mug of 17beta-estradiol were the same for males and females. In an analysis of the effects of neonatal androgenization, Charles River rats were used and it was initially demonstrated that no sex differences in receptor levels existed between normal males and females. After an injection of an androgenizing level of testosterone propionate on day 3 of age, a full normal complement of receptors was found in estrogen-responsive tissues at 90--100 days of age. The functional dynamics of receptor depletion and replenishment under the influence of exogenous estrogen, however, indicated that the anterior pituitary of the androgenized female responded differently from that of the untreated female, and similarly to that of the male. The hypothalamic receptor dynamics in the male were unaltered by early androgen administration, but estrogen-induced depletion of receptors in the female hypothalamus was considerably less extensive in the androgenized animal than in the untreated control. Whereas cytoplasmic estrogen receptor levels are essentially independent of sex in the rat, the present results indicate a sex-linked difference in the dynamics of receptor turnover in the anterior pituitary and hypothalamic response to 17beta-estradiol.", "contents": "Sex-related differences in the regulation of cytoplasmic estrogen receptor levels in responsive tissues of the rat. Cytoplasmic estrogen receptors were measured in the anterior pituitary and hypothalamus of intact adult Holtzman male and female rats at various time intervals following injection of 10 mug of 17beta-estradiol. Following equivalent depletion of receptors at 1 h in either sex, replenishment of cytosol receptor levels progressed at a greater rate and to a higher level in the male than in the female. Cycloheximide only partially inhibited replenishment, and its blocking effect was similar in males and females. The administration of 5 mug of 17beta-estradiol to adult males elicited less depletion than did 10 mug, and a completely cycloheximide-sensitive replenishment phase. Patterns of depletion and replenishment in immature rats following 0.1 mug of 17beta-estradiol were the same for males and females. In an analysis of the effects of neonatal androgenization, Charles River rats were used and it was initially demonstrated that no sex differences in receptor levels existed between normal males and females. After an injection of an androgenizing level of testosterone propionate on day 3 of age, a full normal complement of receptors was found in estrogen-responsive tissues at 90--100 days of age. The functional dynamics of receptor depletion and replenishment under the influence of exogenous estrogen, however, indicated that the anterior pituitary of the androgenized female responded differently from that of the untreated female, and similarly to that of the male. The hypothalamic receptor dynamics in the male were unaltered by early androgen administration, but estrogen-induced depletion of receptors in the female hypothalamus was considerably less extensive in the androgenized animal than in the untreated control. Whereas cytoplasmic estrogen receptor levels are essentially independent of sex in the rat, the present results indicate a sex-linked difference in the dynamics of receptor turnover in the anterior pituitary and hypothalamic response to 17beta-estradiol."} {"id": "PMID:179788", "title": "Androgen and estrogen receptors in brain cytosol from male, female, and testicular feminized (tfm/y hermaphrodite) mice.", "content": "Specific binding of [3H] 5alpha-dihydrotestosterone (DHT) and [3H] estradiol by cytoplasmic extracts from whole brain of castrated male, female, and androgen-insensitive, testicular feminized (tfm/y male-female), mice has been investigated using glycerol gradient centrifugation and charcoal assay. Mouse brain cytosol contains macromolecules with the characteristics of steroid hormone receptors, binding preferentially with high-affinity androgens or estrogens. Both DHT- and estradiol-receptor complexes migrate at 8-9 S in gradients at low ionic strength and at 4-5 S in gradients containing 0.5M KCl. KD's (mean +/- SE) for DHT binding by brain cytosol from castrated males, females, and tfm/y male-female are 1.1 +/- 0.4, 0.9 +/- 0.4, and 0.8 +/- 0.1 X 10(-9)M, respectively. DHT binding activity in brain cytosol from tfm/y male-female mice is reduced to about 20-30% of that from their normal littermates, as is the case for tfm/y male-female kidney cytosol. The residual androgen receptor in tfm/y male-female brain cytosol has normal sedimentation properties. Unlike the situation for androgen binding, the number of estradiol binding sites is comparable in brain cytosol from male, female, and tfm/y male-female mice. KD's (mean +/- SE) for estradiol binding are 1.6 +/- 0.5 X 10(-10)M for castrated males, 2.4 +/- 0.4 X 10(-10)M for females, and 1.8 +/- 0.4 X 10(-10)M for tfm/y male-female. Cross-competition experiments with unlabeled estradiol, DHT, or testosterone, have shown a difference in the degree of specificity of the androgen and estrogen receptors, the estrogen receptor having considerably more specificity. For the interaction of estradiol with the androgen receptor, the Ki is 8-9 X 10(-9)M. The decrease in the number of DHT binding sites in the brain of tfm/y male-female mice without a concomitant decrease in estradiol binding sites, and the different specificities of the two sites, point to the existence of distinct androgen and estrogen receptor molecules in mouse brain cytosol.", "contents": "Androgen and estrogen receptors in brain cytosol from male, female, and testicular feminized (tfm/y hermaphrodite) mice. Specific binding of [3H] 5alpha-dihydrotestosterone (DHT) and [3H] estradiol by cytoplasmic extracts from whole brain of castrated male, female, and androgen-insensitive, testicular feminized (tfm/y male-female), mice has been investigated using glycerol gradient centrifugation and charcoal assay. Mouse brain cytosol contains macromolecules with the characteristics of steroid hormone receptors, binding preferentially with high-affinity androgens or estrogens. Both DHT- and estradiol-receptor complexes migrate at 8-9 S in gradients at low ionic strength and at 4-5 S in gradients containing 0.5M KCl. KD's (mean +/- SE) for DHT binding by brain cytosol from castrated males, females, and tfm/y male-female are 1.1 +/- 0.4, 0.9 +/- 0.4, and 0.8 +/- 0.1 X 10(-9)M, respectively. DHT binding activity in brain cytosol from tfm/y male-female mice is reduced to about 20-30% of that from their normal littermates, as is the case for tfm/y male-female kidney cytosol. The residual androgen receptor in tfm/y male-female brain cytosol has normal sedimentation properties. Unlike the situation for androgen binding, the number of estradiol binding sites is comparable in brain cytosol from male, female, and tfm/y male-female mice. KD's (mean +/- SE) for estradiol binding are 1.6 +/- 0.5 X 10(-10)M for castrated males, 2.4 +/- 0.4 X 10(-10)M for females, and 1.8 +/- 0.4 X 10(-10)M for tfm/y male-female. Cross-competition experiments with unlabeled estradiol, DHT, or testosterone, have shown a difference in the degree of specificity of the androgen and estrogen receptors, the estrogen receptor having considerably more specificity. For the interaction of estradiol with the androgen receptor, the Ki is 8-9 X 10(-9)M. The decrease in the number of DHT binding sites in the brain of tfm/y male-female mice without a concomitant decrease in estradiol binding sites, and the different specificities of the two sites, point to the existence of distinct androgen and estrogen receptor molecules in mouse brain cytosol."} {"id": "PMID:179789", "title": "Activation of thyroid adenyl cyclase by antisera to thyroid plasma membrane preparations.", "content": "Adenyl cyclase was assayed in a series of plasma membrane fractions prepared from bovine thyroids using sucrose density gradient ultracentrifugation. The activity of adenyl cyclase in the plasma membranes was found to be stimulated several-fold by antisera raised in rabbits against the plasma membranes and by purified IgG prepared from these antisera. The data indicate that the antibodies to thyroid plasma membrane manifest properties similar to those of the immunoglobulins long-acting thyroid stimulator (LATS) and human specific thyroid-stimulating immunoglobulin (HTSI) found in patients with Graves' disease. It is suggested that, in these patients, the antigen which leads to the production of LATS and HTSI is most likely situated in the thyroid plasma membrane.", "contents": "Activation of thyroid adenyl cyclase by antisera to thyroid plasma membrane preparations. Adenyl cyclase was assayed in a series of plasma membrane fractions prepared from bovine thyroids using sucrose density gradient ultracentrifugation. The activity of adenyl cyclase in the plasma membranes was found to be stimulated several-fold by antisera raised in rabbits against the plasma membranes and by purified IgG prepared from these antisera. The data indicate that the antibodies to thyroid plasma membrane manifest properties similar to those of the immunoglobulins long-acting thyroid stimulator (LATS) and human specific thyroid-stimulating immunoglobulin (HTSI) found in patients with Graves' disease. It is suggested that, in these patients, the antigen which leads to the production of LATS and HTSI is most likely situated in the thyroid plasma membrane."} {"id": "PMID:179790", "title": "Studies on the corticotrophin-releasing activity of vasopressin, using ACTH secretion by cultured rat adenohypophyseal cells.", "content": "CRF activity of synthetic vasopressins and pitressin was studied in an in vitro system of cultured rat adenohypophyseal cells using direct measurement of ACTH by radioimmunoassay. Pitressin (posterior pituitary extract) induced a dose-related secretion of ACTH whereas synthetic arginine or lysine vasopressin were devoid of CRF activity, even with the largest tested dose (4 mug/ml). No potentiation of the CRF activity of hypothalamic extract was observed with any vasopressin preparation studied. We concluded that: 1) the CRF activity of posterior pituitary extract is not due to vasopressin, and 2) the ACTH secretion induced by vasopressin administration in vivo is unlikely to be due to a direct effect of vasopressin on adenohypophyseal cells.", "contents": "Studies on the corticotrophin-releasing activity of vasopressin, using ACTH secretion by cultured rat adenohypophyseal cells. CRF activity of synthetic vasopressins and pitressin was studied in an in vitro system of cultured rat adenohypophyseal cells using direct measurement of ACTH by radioimmunoassay. Pitressin (posterior pituitary extract) induced a dose-related secretion of ACTH whereas synthetic arginine or lysine vasopressin were devoid of CRF activity, even with the largest tested dose (4 mug/ml). No potentiation of the CRF activity of hypothalamic extract was observed with any vasopressin preparation studied. We concluded that: 1) the CRF activity of posterior pituitary extract is not due to vasopressin, and 2) the ACTH secretion induced by vasopressin administration in vivo is unlikely to be due to a direct effect of vasopressin on adenohypophyseal cells."} {"id": "PMID:179791", "title": "Studies on fast feedback mechanisms by endogenous glucocorticoids.", "content": "Negative feedback in the hypothalamic-pituitary-adrenal axis by exogenous glucocorticoids has been well established, but it is still in doubt whether ACTH-releasing factor (CRF) activity in the hypothalamus is inhibited by endogenous glucocorticoids under conditions of stress. In our first experiment, CRF activity in the hypothalamus of rats was significantly increased, 2 min after onset of immobilization, for 2 min; a rapid drop of CRF activity followed immediately. On the other hand, the concentration of plasma corticosterone changed more slowly; it was increased at 5 min, and showed a progressive further increase until 17 min after the administration of the immobilization stress. A high plateau level persisted for the next 8 min, after which the concentration of plasma corticosterone fell, reaching the control level at 40 min. In order to test for negative feedback inhibition by endogenous glucocorticoids in the hypothalamic-pituitary-adrenal axis, a 2nd immunobilization stress was administered to rats 5 or 23 min after the 1st stress, and hypothalamic CRF activity and plasma corticosterone were examined after the 2nd stress. When the 2nd stress was applied 5 min after the start of the 1st stress, during the phase of a gradual increase of endogenous glucocorticoids, CRF activity was not increased 2 min after the 2nd stress. In contrast, an increase of CRF activity and plasma corticosterone was observed when the 2nd stress was administered 23 min after the onset of the 1st stress, during the phase of a high plateau level of endogenous plasma corticosterone. These data suggest that CRF activity in the hypothalamus is governed by a fast feedback, rate-sensitive mechanism.", "contents": "Studies on fast feedback mechanisms by endogenous glucocorticoids. Negative feedback in the hypothalamic-pituitary-adrenal axis by exogenous glucocorticoids has been well established, but it is still in doubt whether ACTH-releasing factor (CRF) activity in the hypothalamus is inhibited by endogenous glucocorticoids under conditions of stress. In our first experiment, CRF activity in the hypothalamus of rats was significantly increased, 2 min after onset of immobilization, for 2 min; a rapid drop of CRF activity followed immediately. On the other hand, the concentration of plasma corticosterone changed more slowly; it was increased at 5 min, and showed a progressive further increase until 17 min after the administration of the immobilization stress. A high plateau level persisted for the next 8 min, after which the concentration of plasma corticosterone fell, reaching the control level at 40 min. In order to test for negative feedback inhibition by endogenous glucocorticoids in the hypothalamic-pituitary-adrenal axis, a 2nd immunobilization stress was administered to rats 5 or 23 min after the 1st stress, and hypothalamic CRF activity and plasma corticosterone were examined after the 2nd stress. When the 2nd stress was applied 5 min after the start of the 1st stress, during the phase of a gradual increase of endogenous glucocorticoids, CRF activity was not increased 2 min after the 2nd stress. In contrast, an increase of CRF activity and plasma corticosterone was observed when the 2nd stress was administered 23 min after the onset of the 1st stress, during the phase of a high plateau level of endogenous plasma corticosterone. These data suggest that CRF activity in the hypothalamus is governed by a fast feedback, rate-sensitive mechanism."} {"id": "PMID:179792", "title": "In vitro studies on the nature of vinblastine inhibition of thyroid secretion.", "content": "The effects of vinblastine on thyroid secretion have been studied in mouse thyroid glands in vitro. Inhibition of the secretory response to TSH was observed within the first 30 min of exposure to vinblastine and was largely complete after 1 h. Inhibition of colloid droplet formation and hormonal radioiodine release was comparable for both TSH and cyclic AMP stimulation. No reversal of inhibition was seen when thyroids exposed to vinblastine were subsequently washed 2 or 4 h in vinblastine free mediu, nor could previous vinblastine inhibition be overcome by high levels of TSH or dibutyryl cyclic AMP. Ultrastructural effects of vinblastine (1 X 10(-5)M) were studied under conditions similar to those used to demonstrate inhibition of secretion. Microtubules present in thyroids incubated in control medium were reduced after 30 min and almost completely abolished after 1 or 2 h exposure to vinblastine. No other reproducible structural changes were seen. A higher concentration of vinblastine (5 X 10(-5)M), however, produced lysosomal clumping and the formation of numerous vinblastine crystalloids. Uptake and washout of [3H]-vinblastine were studied with both phases showing fast and slow components. The initial uptake phase (T1/2 approximately 12 min) correlates well with the disappearance of microtubules and the inhibition of thyroid secretion. A prolonged washout component (T1/2 = 10-18 h) may account for the irreversibility of vinblastine inhibition of in vitro thyroid secretion. It is concluded that inhibition of thyroid secretion produced by vinblastine is consistent with its actions on thyroidal microtubules.", "contents": "In vitro studies on the nature of vinblastine inhibition of thyroid secretion. The effects of vinblastine on thyroid secretion have been studied in mouse thyroid glands in vitro. Inhibition of the secretory response to TSH was observed within the first 30 min of exposure to vinblastine and was largely complete after 1 h. Inhibition of colloid droplet formation and hormonal radioiodine release was comparable for both TSH and cyclic AMP stimulation. No reversal of inhibition was seen when thyroids exposed to vinblastine were subsequently washed 2 or 4 h in vinblastine free mediu, nor could previous vinblastine inhibition be overcome by high levels of TSH or dibutyryl cyclic AMP. Ultrastructural effects of vinblastine (1 X 10(-5)M) were studied under conditions similar to those used to demonstrate inhibition of secretion. Microtubules present in thyroids incubated in control medium were reduced after 30 min and almost completely abolished after 1 or 2 h exposure to vinblastine. No other reproducible structural changes were seen. A higher concentration of vinblastine (5 X 10(-5)M), however, produced lysosomal clumping and the formation of numerous vinblastine crystalloids. Uptake and washout of [3H]-vinblastine were studied with both phases showing fast and slow components. The initial uptake phase (T1/2 approximately 12 min) correlates well with the disappearance of microtubules and the inhibition of thyroid secretion. A prolonged washout component (T1/2 = 10-18 h) may account for the irreversibility of vinblastine inhibition of in vitro thyroid secretion. It is concluded that inhibition of thyroid secretion produced by vinblastine is consistent with its actions on thyroidal microtubules."} {"id": "PMID:179793", "title": "Luteotropic regulation of dispersed rat luteal cells in early pregnancy.", "content": "Viable and functional luteal cells were prepared, using a combination of hyaluronidase, collagenase, and a low concentration of trypsin in a Dulbecco's modified Eagle medium containing 0.5% bovine serum albumin and 3.3 mM Ca++, from corpora lutea taken from 2-day pregnant rats. The viability and functional capacity of the dispersed cells were evaluated by electronmicroscopy and by measuring steroidogenic capicity during perifusion. Dispersed luteal cells previously exposed in vivo to biphasic prolactin (PRL) surges were found to respond during perifusion to as little as 0.5 ng/ml LH by increased steroid secretion. The net progesterone synthesis and secretion remained elevated over a time course of 2 1/2 hours perifusion, and the magnitude of the luteotropic stimulation was dose dependent on LH. However, luteotropic stimulation of LH could not be maintained beyond 2 1/2 h without renewed (in vitro) PRL exposure. PRL by itself maintained the low initial secretion rate of progesterone but demonstrated no stimulatory effect. Different steroidogenic responses were noted during the in vitro administration of LH alone and the administration of LH plus PRL. In the former case, the decreasing rate of progesterone secretion was accompanied by an increasing 20 alpha-dihydroprogesterone secretion, suggesting that luteal 20 alpha-hydroxysteroid dehydrogenase activity was not suppressed. In the latter case, progesterone secretion was maintained and 20 alpha-dihydroprogesterone secretion fell suggesting an inhibitory action by PRL against 20 alpha-hydroxysteroid dehydrogenase activity. Dispersed luteal cells, preincubated at 36 C in medium containing only PRL, retained viability and functional capacity in response to LH-PRL stimulation for periods of time up to 48 h. Preincubation with LH alone did not prolong cell viability.", "contents": "Luteotropic regulation of dispersed rat luteal cells in early pregnancy. Viable and functional luteal cells were prepared, using a combination of hyaluronidase, collagenase, and a low concentration of trypsin in a Dulbecco's modified Eagle medium containing 0.5% bovine serum albumin and 3.3 mM Ca++, from corpora lutea taken from 2-day pregnant rats. The viability and functional capacity of the dispersed cells were evaluated by electronmicroscopy and by measuring steroidogenic capicity during perifusion. Dispersed luteal cells previously exposed in vivo to biphasic prolactin (PRL) surges were found to respond during perifusion to as little as 0.5 ng/ml LH by increased steroid secretion. The net progesterone synthesis and secretion remained elevated over a time course of 2 1/2 hours perifusion, and the magnitude of the luteotropic stimulation was dose dependent on LH. However, luteotropic stimulation of LH could not be maintained beyond 2 1/2 h without renewed (in vitro) PRL exposure. PRL by itself maintained the low initial secretion rate of progesterone but demonstrated no stimulatory effect. Different steroidogenic responses were noted during the in vitro administration of LH alone and the administration of LH plus PRL. In the former case, the decreasing rate of progesterone secretion was accompanied by an increasing 20 alpha-dihydroprogesterone secretion, suggesting that luteal 20 alpha-hydroxysteroid dehydrogenase activity was not suppressed. In the latter case, progesterone secretion was maintained and 20 alpha-dihydroprogesterone secretion fell suggesting an inhibitory action by PRL against 20 alpha-hydroxysteroid dehydrogenase activity. Dispersed luteal cells, preincubated at 36 C in medium containing only PRL, retained viability and functional capacity in response to LH-PRL stimulation for periods of time up to 48 h. Preincubation with LH alone did not prolong cell viability."} {"id": "PMID:179794", "title": "Water-soluble specific growth hormone binding sites from cultured human lymphocytes: preparation and partial characterization.", "content": "Cultured human lymphocytes (IM-9 cell line) have specific binding sites or receptors for human growth hormone (hGH). Under appropriate conditions, this specific binding material is spontaneously released into the incubation medium and is solubilized without the use of detergents. This water-soluble preparation binds [125I]iodo-hGH with the same specifictiy as receptors on the intact cell. Unlabeled hGH, but not porcine growth hormone or insulin, competes with labeled hGH for binding to the soluble preparation. Growth hormone preparations of varying purity compete for binding to the soluble binding preparation in the same rank order as they compete for binding to the intact IM-9 lymphocyte. [125I]iodo-hGH incubated with, but not bound to, the soluble preparation is partially degraded, while the [125I]iodo-hGH that is bound to the soluble preparation is protected from degradation, and its ability to rebind to fresh cells is enhanced. The [125I]iodo-hGH-soluble binding preparation complex can be dissociated by the addition of large quantities of unlabeled hGH or by lowering the pH, and [125I]iodo-hGH in both instances remains intact and undegraded. The soluble binding preparation did not sediment when centrifuged at 200,000 X g for 4 hours and was not retained on 0.20 micron Millipore filters. The soluble binding preparation was not retarded on Sephadex G-200. Binding activity was abolished by tryptic digestion. These studies demonstrate that hGH-binding sites, like previously reported insulin binding sites, can be spontaneously solubilized from cultured human lymphocytes, without the use of detergents; these soluble binding preparations are of high molecular weight and are, at least in part, protein in nature.", "contents": "Water-soluble specific growth hormone binding sites from cultured human lymphocytes: preparation and partial characterization. Cultured human lymphocytes (IM-9 cell line) have specific binding sites or receptors for human growth hormone (hGH). Under appropriate conditions, this specific binding material is spontaneously released into the incubation medium and is solubilized without the use of detergents. This water-soluble preparation binds [125I]iodo-hGH with the same specifictiy as receptors on the intact cell. Unlabeled hGH, but not porcine growth hormone or insulin, competes with labeled hGH for binding to the soluble preparation. Growth hormone preparations of varying purity compete for binding to the soluble binding preparation in the same rank order as they compete for binding to the intact IM-9 lymphocyte. [125I]iodo-hGH incubated with, but not bound to, the soluble preparation is partially degraded, while the [125I]iodo-hGH that is bound to the soluble preparation is protected from degradation, and its ability to rebind to fresh cells is enhanced. The [125I]iodo-hGH-soluble binding preparation complex can be dissociated by the addition of large quantities of unlabeled hGH or by lowering the pH, and [125I]iodo-hGH in both instances remains intact and undegraded. The soluble binding preparation did not sediment when centrifuged at 200,000 X g for 4 hours and was not retained on 0.20 micron Millipore filters. The soluble binding preparation was not retarded on Sephadex G-200. Binding activity was abolished by tryptic digestion. These studies demonstrate that hGH-binding sites, like previously reported insulin binding sites, can be spontaneously solubilized from cultured human lymphocytes, without the use of detergents; these soluble binding preparations are of high molecular weight and are, at least in part, protein in nature."} {"id": "PMID:179795", "title": "Effects of parathyroid hormone in vivo on the protein kinase activity in rat kidney.", "content": "Parathyroid hormone (PTH) was infused into thyroparathyroidectomized rats, and the protein kinase activity of the kidney was studied. When the tissue was homogenized in a buffer containing 5 mM potassium phosphate (pH 7.0), 2 mM EDTA, 1 mM mercaptoethanol, and 5 mM theophylline, the total protein kinase activity (measured in the presence of 5 muM cAMP) in the cytosol was decreased by the infusion of PTH, exhibiting an inverse relationship to cAMP level in the renal tissue. The decrease of total activity was accounted for by a decrease of cAMP-dependent kinase activity, and such a change was induced also by the infusion of calcitonin or dibutyryl cAMP. A substantial enzyme activity was solubilized from the particulate fraction with a buffer containing KC1. The infusion of PTH increased the kinase activity (activities measured in both the presence and absence of cAMP) solubilized from the particulate fraction, suggesting the translocation of activated enzyme from cytosol to some particulate cell component(s). However, when KC1 was added to the homogenization buffer in concentrations up to 150 mM or even higher, the total protein kianse activities in the cytosols of control and PTH rats were similar and there was simply an increase in the fraction of cAMP -independent activity. These observations indicate that the hormonally-induced increase of cAMP in vivo activates protein kinase of the kidney, and the activation of kinase results in apparent translocation of the enzyme from the soluble to the particulate fraction when the tissue is homogenized in buffers of low ionic strength. The physiological significance of this phenomenon, however, cannot be evaluated, due to the fact that the increased association of activated kinase with particulate component(s) is reversed by employing a homogenization buffer containing what is probably a physiological concentration of salt.", "contents": "Effects of parathyroid hormone in vivo on the protein kinase activity in rat kidney. Parathyroid hormone (PTH) was infused into thyroparathyroidectomized rats, and the protein kinase activity of the kidney was studied. When the tissue was homogenized in a buffer containing 5 mM potassium phosphate (pH 7.0), 2 mM EDTA, 1 mM mercaptoethanol, and 5 mM theophylline, the total protein kinase activity (measured in the presence of 5 muM cAMP) in the cytosol was decreased by the infusion of PTH, exhibiting an inverse relationship to cAMP level in the renal tissue. The decrease of total activity was accounted for by a decrease of cAMP-dependent kinase activity, and such a change was induced also by the infusion of calcitonin or dibutyryl cAMP. A substantial enzyme activity was solubilized from the particulate fraction with a buffer containing KC1. The infusion of PTH increased the kinase activity (activities measured in both the presence and absence of cAMP) solubilized from the particulate fraction, suggesting the translocation of activated enzyme from cytosol to some particulate cell component(s). However, when KC1 was added to the homogenization buffer in concentrations up to 150 mM or even higher, the total protein kianse activities in the cytosols of control and PTH rats were similar and there was simply an increase in the fraction of cAMP -independent activity. These observations indicate that the hormonally-induced increase of cAMP in vivo activates protein kinase of the kidney, and the activation of kinase results in apparent translocation of the enzyme from the soluble to the particulate fraction when the tissue is homogenized in buffers of low ionic strength. The physiological significance of this phenomenon, however, cannot be evaluated, due to the fact that the increased association of activated kinase with particulate component(s) is reversed by employing a homogenization buffer containing what is probably a physiological concentration of salt."} {"id": "PMID:179796", "title": "Daily variation in concentration of plasma corticosteroid in hypophysectomized rats.", "content": "A daily variation in the concentration of plasma corticosteroid hormone is present in hypophysectomized rats implanted with pellets of adrenocorticotropic hormone (ACTH) and thyroxine. Although ACTH is necessary to maintain a functional adrenal, and thyroxine is required to permit the expression of the plasma corticosteroid rhythm, a normal daily variation in plasma corticosteroid concentration does not appear to depend on the periodic release of pituitary hormones.", "contents": "Daily variation in concentration of plasma corticosteroid in hypophysectomized rats. A daily variation in the concentration of plasma corticosteroid hormone is present in hypophysectomized rats implanted with pellets of adrenocorticotropic hormone (ACTH) and thyroxine. Although ACTH is necessary to maintain a functional adrenal, and thyroxine is required to permit the expression of the plasma corticosteroid rhythm, a normal daily variation in plasma corticosteroid concentration does not appear to depend on the periodic release of pituitary hormones."} {"id": "PMID:179797", "title": "Possible sequential transformation of a series of acidophils in the pituitary autografts in the renal capsule of male rats in association with ACTH cell.", "content": "In our electron microscopy, acidiphils in the pituitary autografts placed in the renal capsules of immature male rats underwent a sequential transformation with the lapse of time: Within 3 and 6 days, all the somaotrophs packed with the large granules of about 350 mmu diameter dispersed. The size and number of the granules in somatotrophs were quickly and markedly reduced with severe modification of cell shape. There was evidence during this time course that Siperstein's or Moriarty's corticotrophs might be synonymous with the stellate shape of acidophils with the arrangement of small granules 150-200 mmu in diameter along the cell acidophils. The \"acidophils of the small granule type\" possibly related to ACTH production according to Yoshimura et al. (1974) were frequently detected in the grafts as elongated or irregularly shaped cells. Their minute granules 100-150 mmu in diameter were also distributed in row in the cytoplasmic peripheral area. Gradual loss of the minute granules below 100 mmu in diameter eventually made the acidophils to transform into agranular cells. Our own idea that ACTH secretion might correlate with a series of cells transforming along the acidophil-axis was indirectly supported by the present observation on pituitary grafts. On the other hand, basophils rapidly degenerated and died away. Ten and 20 days after autografting, the graft cells which might be principally composed of the cells of acidophil origin enormously proliferated through mitotic division, showing the homologous fine structure, without the normal cell individuality. They always contained three different size and shape of granules simulataneously. Significance of such a rapid and strong response of acidophils to the ectopic replacement in the immature male rats was discussed from the view-point of hypothalamic regulation to simple protein hormones.", "contents": "Possible sequential transformation of a series of acidophils in the pituitary autografts in the renal capsule of male rats in association with ACTH cell. In our electron microscopy, acidiphils in the pituitary autografts placed in the renal capsules of immature male rats underwent a sequential transformation with the lapse of time: Within 3 and 6 days, all the somaotrophs packed with the large granules of about 350 mmu diameter dispersed. The size and number of the granules in somatotrophs were quickly and markedly reduced with severe modification of cell shape. There was evidence during this time course that Siperstein's or Moriarty's corticotrophs might be synonymous with the stellate shape of acidophils with the arrangement of small granules 150-200 mmu in diameter along the cell acidophils. The \"acidophils of the small granule type\" possibly related to ACTH production according to Yoshimura et al. (1974) were frequently detected in the grafts as elongated or irregularly shaped cells. Their minute granules 100-150 mmu in diameter were also distributed in row in the cytoplasmic peripheral area. Gradual loss of the minute granules below 100 mmu in diameter eventually made the acidophils to transform into agranular cells. Our own idea that ACTH secretion might correlate with a series of cells transforming along the acidophil-axis was indirectly supported by the present observation on pituitary grafts. On the other hand, basophils rapidly degenerated and died away. Ten and 20 days after autografting, the graft cells which might be principally composed of the cells of acidophil origin enormously proliferated through mitotic division, showing the homologous fine structure, without the normal cell individuality. They always contained three different size and shape of granules simulataneously. Significance of such a rapid and strong response of acidophils to the ectopic replacement in the immature male rats was discussed from the view-point of hypothalamic regulation to simple protein hormones."} {"id": "PMID:179798", "title": "Reduction of 5'-nucleotidase activity in rat thyroid and adenohypophysis following methylthiouracil treatment.", "content": "5' -Nucleotidase activity was determined in rat thyroid and some other organs employing a specific assay method. During the course of methylthiouracil (MTU) treatment, thyroid 5'-nucleotidase activity decreased significantly. This decrease was specific for this enzyme since the activity of neutral phosphatase did not change and the activity of alkaline phosphatase and Mg2+-activated adenosine triphosphatase increased markedly. The 5'-nucleotidase activity of the adenohypophysis also decreased following MTU treatment. This enzyme activity of the liver, heart and whole brain remained unchanged after the treatment. The role of this enzyme was discussed in relation to tissue growth and increased contents of RNA and DNA in the thyroid and adenohypophysis.", "contents": "Reduction of 5'-nucleotidase activity in rat thyroid and adenohypophysis following methylthiouracil treatment. 5' -Nucleotidase activity was determined in rat thyroid and some other organs employing a specific assay method. During the course of methylthiouracil (MTU) treatment, thyroid 5'-nucleotidase activity decreased significantly. This decrease was specific for this enzyme since the activity of neutral phosphatase did not change and the activity of alkaline phosphatase and Mg2+-activated adenosine triphosphatase increased markedly. The 5'-nucleotidase activity of the adenohypophysis also decreased following MTU treatment. This enzyme activity of the liver, heart and whole brain remained unchanged after the treatment. The role of this enzyme was discussed in relation to tissue growth and increased contents of RNA and DNA in the thyroid and adenohypophysis."} {"id": "PMID:179799", "title": "Role of sodium and potassium in aldosterone binding of kidney receptors in the rat.", "content": "An increase of the sodium concentration produced a diminished binding of labeled aldosterone to kidney receptors in both in vivo and in vitro conditions. The elevation of potassium level did not change the binding capacity of kidney nuclear receptors for aldosterone. Hypernatraemia-induced decrease of aldosterone uptake was significant in the nuclear fraction of both medullary and cortical region of the kidney but did not show remarkable changes in the uptake of cytosol fraction. The transfer of aldosterone from cytosol into the nuclear compartment seems to be changed by the alteration of extracellular sodium concentration.", "contents": "Role of sodium and potassium in aldosterone binding of kidney receptors in the rat. An increase of the sodium concentration produced a diminished binding of labeled aldosterone to kidney receptors in both in vivo and in vitro conditions. The elevation of potassium level did not change the binding capacity of kidney nuclear receptors for aldosterone. Hypernatraemia-induced decrease of aldosterone uptake was significant in the nuclear fraction of both medullary and cortical region of the kidney but did not show remarkable changes in the uptake of cytosol fraction. The transfer of aldosterone from cytosol into the nuclear compartment seems to be changed by the alteration of extracellular sodium concentration."} {"id": "PMID:179800", "title": "Steroid production by quartered and capsular rat adrenal gland in response to haemorrhage.", "content": "60 min after rapid bleeding (1.5--2.0 per cent of b. w.) both aldosterone and corticosterone production rate by quartered rat adrenals were found to be elevated. However, no difference was observed in the rate of aldosterone and corticosterone production by capsular adrenals of sham operated and hypovolaemic rats. Corticosterone production rate by decapsulated adrenals was much more higher after haemorrhage than in the control group. The same alterations could be observed incubating adrenal tissue with ACTH (0.3 mug per ml). Steroid production rate by quartered adrenals of sodium deficient rats was not affected by high in vitro concentration of angiotensin II (2.5 mug per ml). It is concluded that the effect of acute blood loss on corticosteroid biosynthesis of the rat is mediated by ACTH alone.", "contents": "Steroid production by quartered and capsular rat adrenal gland in response to haemorrhage. 60 min after rapid bleeding (1.5--2.0 per cent of b. w.) both aldosterone and corticosterone production rate by quartered rat adrenals were found to be elevated. However, no difference was observed in the rate of aldosterone and corticosterone production by capsular adrenals of sham operated and hypovolaemic rats. Corticosterone production rate by decapsulated adrenals was much more higher after haemorrhage than in the control group. The same alterations could be observed incubating adrenal tissue with ACTH (0.3 mug per ml). Steroid production rate by quartered adrenals of sodium deficient rats was not affected by high in vitro concentration of angiotensin II (2.5 mug per ml). It is concluded that the effect of acute blood loss on corticosteroid biosynthesis of the rat is mediated by ACTH alone."} {"id": "PMID:179801", "title": "Hormone receptor studies on frog macrophage cells by means of histamine, serotonin and indoleacetic acid.", "content": "The phagocytotic activity of frog macrophage cells could be increased by 50% with histamine and by 24% with serotonin. These hormones have a similar effect at the various stages of phylogenetic development, to judge from the respective responses of the unicellular Tetrahymena which showed roughly the same percentual increases of phagocytosis as frog macrophages at roughly the same hormone concentrations. It is concluded that cytoplasmic membrane receptor patterns for a given function do not change in the course of phylogenetic development and the receptors have a capacity for selection, preferring histamine to serotonin, and the latter to the chemically closely related plant hormone indoleacetic acid.", "contents": "Hormone receptor studies on frog macrophage cells by means of histamine, serotonin and indoleacetic acid. The phagocytotic activity of frog macrophage cells could be increased by 50% with histamine and by 24% with serotonin. These hormones have a similar effect at the various stages of phylogenetic development, to judge from the respective responses of the unicellular Tetrahymena which showed roughly the same percentual increases of phagocytosis as frog macrophages at roughly the same hormone concentrations. It is concluded that cytoplasmic membrane receptor patterns for a given function do not change in the course of phylogenetic development and the receptors have a capacity for selection, preferring histamine to serotonin, and the latter to the chemically closely related plant hormone indoleacetic acid."} {"id": "PMID:179803", "title": "The role of the adrenal gland in the lipid accumulation process in the liver of rats bearing an acth and prolactin producing tumor.", "content": "The role of the adrenal glands in the development of fatty liver was investigated in rats bearing a transplantable pituitary mammotropic tumor which produces large quantities of ACTH and prolactin. The biochemical and histochemical and histochemical evidence obtained has demonstrated that the adrenal glands, particularly glucocorticoids, are essential for lipid accumulation in the liver of rats with tumor.", "contents": "The role of the adrenal gland in the lipid accumulation process in the liver of rats bearing an acth and prolactin producing tumor. The role of the adrenal glands in the development of fatty liver was investigated in rats bearing a transplantable pituitary mammotropic tumor which produces large quantities of ACTH and prolactin. The biochemical and histochemical and histochemical evidence obtained has demonstrated that the adrenal glands, particularly glucocorticoids, are essential for lipid accumulation in the liver of rats with tumor."} {"id": "PMID:179804", "title": "Protective value of dietary copper and iron against some toxic effects of lead in rats.", "content": "Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depressed when dietary iron was low, a condition which was worsened by lead. Lead tended to lower heart cytochrome c oxidase especially when dietary copper was low, but also when dietary copper and zinc were high. Lead interfered with hematopoiesis when dietary copper and/or iron were low, the effect being expecially severe when both essential nutrients were low. These results show the importance of copper and iron nutriture and metabolism as factors which reduce lead toxicity, and emphasize the necessity of considering nutritional status in evaluating lead toxicity.", "contents": "Protective value of dietary copper and iron against some toxic effects of lead in rats. Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depressed when dietary iron was low, a condition which was worsened by lead. Lead tended to lower heart cytochrome c oxidase especially when dietary copper was low, but also when dietary copper and zinc were high. Lead interfered with hematopoiesis when dietary copper and/or iron were low, the effect being expecially severe when both essential nutrients were low. These results show the importance of copper and iron nutriture and metabolism as factors which reduce lead toxicity, and emphasize the necessity of considering nutritional status in evaluating lead toxicity."} {"id": "PMID:179805", "title": "Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. II. Human viral hepatitis and cirrhosis of the liver.", "content": "Activities of key carbohydrate-metabolizing enzymes were determined on biopsied liver tissues obtained from patients with acute and chronic viral hepatitis and postnecrotic cirrhosis of the liver. The results indicated that the activities of fetal or prototype enzymes, low-Km hexokinases, glucose-6-phosphate dehydrogenase and pyruvate kinase type M2 increased, while those of adult type liver enzymes, glucokinase, glucose-6-phosphatase, fructose-1, 6-diphosphatase and pyruvate kinase type L decreased in livers of these cases. Phosphofructokinase activity tended to increase only acute hepatitis. Principal component analysis revealed that the enzyme patterns of acute hepatitis and liver cirrhosis were most deviated from the control and closely resembled those of hepatocellular carcinomas.", "contents": "Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. II. Human viral hepatitis and cirrhosis of the liver. Activities of key carbohydrate-metabolizing enzymes were determined on biopsied liver tissues obtained from patients with acute and chronic viral hepatitis and postnecrotic cirrhosis of the liver. The results indicated that the activities of fetal or prototype enzymes, low-Km hexokinases, glucose-6-phosphate dehydrogenase and pyruvate kinase type M2 increased, while those of adult type liver enzymes, glucokinase, glucose-6-phosphatase, fructose-1, 6-diphosphatase and pyruvate kinase type L decreased in livers of these cases. Phosphofructokinase activity tended to increase only acute hepatitis. Principal component analysis revealed that the enzyme patterns of acute hepatitis and liver cirrhosis were most deviated from the control and closely resembled those of hepatocellular carcinomas."} {"id": "PMID:179806", "title": "Factors influencing the establishment of the normal values of the respiratory activities of human liver mitochondria.", "content": "Some factors that influence the values of respiratory activities of liver mitochondria isolated from surgical biopsy specimens have been studied. By sedimentating of mitochondria at a lower centrifugal force (5,500 g) than usually used for rat liver mitochondria, and washing the mitochondrial pellet twice, the contamination with lysosomes and microsomes was lowered. At 37 degrees C, and in the presence of hexokinase and glucose, the oxygen uptake was greater than at 25 degrees C and in their absence. The respiratory control was good and the respiratory activities were rather stable during the first 3-4 h after isolation. The respiratory activities of mitochondria isolated from patients with duodenal or gastric ulcers, biliary diseases, and subjects with no digestive diseases (all having normal liver) were compared. Differences in oxygen uptake and acceptor control index values with some substrates were noted. The conditions for selection of controls in studies on subcellular fractions of human liver include: absence of any hepatic antecedents; no clinical evidence of liver involvement; no abnormality in routine liver function tests; a histologic aspect free of pathological conditions, and a normal aspect of the tissue during the homogenization and the fractionation procedure (absence of steatosis or fibrosis). These data provide a basis for the standardization of methods in establishing the reference values of mitochondrial activities for the modifications in a variety of diseases.", "contents": "Factors influencing the establishment of the normal values of the respiratory activities of human liver mitochondria. Some factors that influence the values of respiratory activities of liver mitochondria isolated from surgical biopsy specimens have been studied. By sedimentating of mitochondria at a lower centrifugal force (5,500 g) than usually used for rat liver mitochondria, and washing the mitochondrial pellet twice, the contamination with lysosomes and microsomes was lowered. At 37 degrees C, and in the presence of hexokinase and glucose, the oxygen uptake was greater than at 25 degrees C and in their absence. The respiratory control was good and the respiratory activities were rather stable during the first 3-4 h after isolation. The respiratory activities of mitochondria isolated from patients with duodenal or gastric ulcers, biliary diseases, and subjects with no digestive diseases (all having normal liver) were compared. Differences in oxygen uptake and acceptor control index values with some substrates were noted. The conditions for selection of controls in studies on subcellular fractions of human liver include: absence of any hepatic antecedents; no clinical evidence of liver involvement; no abnormality in routine liver function tests; a histologic aspect free of pathological conditions, and a normal aspect of the tissue during the homogenization and the fractionation procedure (absence of steatosis or fibrosis). These data provide a basis for the standardization of methods in establishing the reference values of mitochondrial activities for the modifications in a variety of diseases."} {"id": "PMID:179807", "title": "Plastocyanin: possible significance of quaternary structure.", "content": "Some properties of the blue copper protein plastocyanin from the green alga Scenedesmus have been investigated and compared with that from spinach, including amino acid composition, isoelectric point and copper content. The protein from Scenedesmus contains two, that from spinach four copper atoms per molecular weight of 40000. A combination of sodium dodecylsulfate/polyacrylamide gel electrophoresis and quantification of sulfhydryl groups indicates a strong preference for a species composed of 4 polypeptide chains of identical amino acid composition representing the enzymically active entity. Due to various treatments the subunits of both plastocyanins are detected as either monomer species alone or as monomer and dimer in a molar ratio of 2 : 1 on sodium dodecylsulfate gels. The four -SH groups per molecule are of different reactivity: two -SH groups can be detected after destruction of the chromophore; two more (forming an S-S bridge in the dimer) become evident after appropriate reduction. A KCN treatment for production of apoprotein is reported and the use of electrodialysis to improve incomplete apoprotein formation. These studies lend support to the proposal of a quaternary structure. Apoproteins were subjected to dodecylsulfate gel analysis, which proved to be an effective means of estimating both the extent of apoprotein formation and its reconstitution to the haloprotein.", "contents": "Plastocyanin: possible significance of quaternary structure. Some properties of the blue copper protein plastocyanin from the green alga Scenedesmus have been investigated and compared with that from spinach, including amino acid composition, isoelectric point and copper content. The protein from Scenedesmus contains two, that from spinach four copper atoms per molecular weight of 40000. A combination of sodium dodecylsulfate/polyacrylamide gel electrophoresis and quantification of sulfhydryl groups indicates a strong preference for a species composed of 4 polypeptide chains of identical amino acid composition representing the enzymically active entity. Due to various treatments the subunits of both plastocyanins are detected as either monomer species alone or as monomer and dimer in a molar ratio of 2 : 1 on sodium dodecylsulfate gels. The four -SH groups per molecule are of different reactivity: two -SH groups can be detected after destruction of the chromophore; two more (forming an S-S bridge in the dimer) become evident after appropriate reduction. A KCN treatment for production of apoprotein is reported and the use of electrodialysis to improve incomplete apoprotein formation. These studies lend support to the proposal of a quaternary structure. Apoproteins were subjected to dodecylsulfate gel analysis, which proved to be an effective means of estimating both the extent of apoprotein formation and its reconstitution to the haloprotein."} {"id": "PMID:179808", "title": "The influence of insulin on various enzyme activities in human and rat hepatoma cells.", "content": "1. Incubation of human and rat hepatoma cells with insulin (1 mU/10(6) cells) decreases their content of adenosine 3':5'-monophosphate by more than half after 1 h and by about a quarter after 4 h. 2. The activities of the ATP-metabolising enzymes, adenylate kinase and Mg2+-adenosine triphosphatase are significantly increased by insulin within 1 h and after 4 h. Activity of succinate dehydrogenase and lactic dehydrogenase showed no change at either time interval. 3. Insulin markedly stimulated glucose 6-phosphate dehydrogenase activity within 1 h but by 4 h the increase was less apparent. Glutamate dehydrogenase activity by contrast was not increased by 1 h but was elevated at 4 h.", "contents": "The influence of insulin on various enzyme activities in human and rat hepatoma cells. 1. Incubation of human and rat hepatoma cells with insulin (1 mU/10(6) cells) decreases their content of adenosine 3':5'-monophosphate by more than half after 1 h and by about a quarter after 4 h. 2. The activities of the ATP-metabolising enzymes, adenylate kinase and Mg2+-adenosine triphosphatase are significantly increased by insulin within 1 h and after 4 h. Activity of succinate dehydrogenase and lactic dehydrogenase showed no change at either time interval. 3. Insulin markedly stimulated glucose 6-phosphate dehydrogenase activity within 1 h but by 4 h the increase was less apparent. Glutamate dehydrogenase activity by contrast was not increased by 1 h but was elevated at 4 h."} {"id": "PMID:179809", "title": "The prosthetic group of citrate-lyase acyl-carrier protein.", "content": "The acyl carrier protein of citrate lyase contains adenine, phosphate, sugar, cysteamine, beta-alanine and pantoic acid in a molar ratio of 1:2:2:1:1:1. Peptides containing these components in the same stoichiometric relationship were isolated after proteolytic digestion of acyl carrier protein. All components were linked together in a single prosthetic group. This was released from the peptide by mild alkaline hydrolysis. Under these conditions a phosphodiester bond is cleaved which links the prosthetic group to a serine residue of the peptide. Incubation of the prosthetic-group-containing peptide with phosphodiesterase I yielded 4'-phosphopantetheine and adenylic acid. The 5'-AMP was not free but was substituted by presumably an acidic sugar residue, which was released by mild acid hydrolysis yielding free 5'-AMP. It was concluded from these results that the prosthetic group of citrate lyase acyl carrier protein consists of a substituted isomeric dephospho-CoA. This is bound to the protein by the 5'-phosphate group of adenylic acid. The 4'-phosphopantetheine residue is bound by a phosphodiester linkage to the 2' or 3' position of ribose and the remaining hydroxyl group of ribose is substituted with presumably an acidic sugar residue. The structural similarities of this prothetic group and coenzyme A are discussed and related to the catalytic properties of citrate lyase.", "contents": "The prosthetic group of citrate-lyase acyl-carrier protein. The acyl carrier protein of citrate lyase contains adenine, phosphate, sugar, cysteamine, beta-alanine and pantoic acid in a molar ratio of 1:2:2:1:1:1. Peptides containing these components in the same stoichiometric relationship were isolated after proteolytic digestion of acyl carrier protein. All components were linked together in a single prosthetic group. This was released from the peptide by mild alkaline hydrolysis. Under these conditions a phosphodiester bond is cleaved which links the prosthetic group to a serine residue of the peptide. Incubation of the prosthetic-group-containing peptide with phosphodiesterase I yielded 4'-phosphopantetheine and adenylic acid. The 5'-AMP was not free but was substituted by presumably an acidic sugar residue, which was released by mild acid hydrolysis yielding free 5'-AMP. It was concluded from these results that the prosthetic group of citrate lyase acyl carrier protein consists of a substituted isomeric dephospho-CoA. This is bound to the protein by the 5'-phosphate group of adenylic acid. The 4'-phosphopantetheine residue is bound by a phosphodiester linkage to the 2' or 3' position of ribose and the remaining hydroxyl group of ribose is substituted with presumably an acidic sugar residue. The structural similarities of this prothetic group and coenzyme A are discussed and related to the catalytic properties of citrate lyase."} {"id": "PMID:179810", "title": "Phosphatidic acid metabolism in rat liver microsomes.", "content": "Rat liver microsomes contain phosphatidate phosphatases which split phosphatidic acid into inorganic phosphate and diacylglycerol and a system of phospholipases and lipases, which split phosphatidic acid into free fatty acids, glycerol and inorganic phosphate. In the presence of ATP,CoA and [1-14C]palmitate, part of the monoacyl-sn-glycerol 3-phosphate formed by phospholipase action is reesterified, yielding radioactive phosphatidic acid. The sum of di- and triacylglycerols formed from phosphatidic acid in the presence of ATP and CoA exceeded the amount of diacylglycerol formed in their absence. The yield of neutral lipids from sn-glycerol 3-phosphate and monoacyl-sn-glycerol 3-phosphate markedly exceeded that from phosphatidic acid. Comparison of the yields of di- and triacylglcerols from glycerol-labelled and fatty-acid-labelled phosphatidic acid was used to establish the extent of deacylation and reacylation. About 60% of the diacylglycerol was formed by direct dephosphorylation. The triacylglycerols, on the other hand, were formed almost exclusively from recycled phosphatidic acid.", "contents": "Phosphatidic acid metabolism in rat liver microsomes. Rat liver microsomes contain phosphatidate phosphatases which split phosphatidic acid into inorganic phosphate and diacylglycerol and a system of phospholipases and lipases, which split phosphatidic acid into free fatty acids, glycerol and inorganic phosphate. In the presence of ATP,CoA and [1-14C]palmitate, part of the monoacyl-sn-glycerol 3-phosphate formed by phospholipase action is reesterified, yielding radioactive phosphatidic acid. The sum of di- and triacylglycerols formed from phosphatidic acid in the presence of ATP and CoA exceeded the amount of diacylglycerol formed in their absence. The yield of neutral lipids from sn-glycerol 3-phosphate and monoacyl-sn-glycerol 3-phosphate markedly exceeded that from phosphatidic acid. Comparison of the yields of di- and triacylglcerols from glycerol-labelled and fatty-acid-labelled phosphatidic acid was used to establish the extent of deacylation and reacylation. About 60% of the diacylglycerol was formed by direct dephosphorylation. The triacylglycerols, on the other hand, were formed almost exclusively from recycled phosphatidic acid."} {"id": "PMID:179811", "title": "Studies on the mechanism of site I energy conservation.", "content": "1. Of the several iron-sulfur centers detected in the site I segment of the respiratory chain, centers N-2 and N-1a alone exhibit apparent phosphate-potential dependent half-reduction potentials, indicating their possible involvement in energy conservation. 2. At high phosphate potential, the apparent half-reduction potential of center N-2 shifts positively by 125 +/- 20 mV, while center N-1a shifts negatively by approximately 60 mV. 3. The redox state of individual iron-sulfur centers in various metabolic states was analyzed. Center N-2 is highly reduced (greater than 90%) in \"state 4\" mitochondria, while center N-1a stays mostly oxidized. 4. In a submitochondrial system, ATP addition induced reduction of center N-2 if the Eh of the suspension was poised from the high potential side of site I using the succinate/fumarate couple. In contrast, center N-2 was oxidized upon energization, if the Eh of the system was poised from the low potential side using the NADH/NAD couple. 5. Based on these redox behaviors of center N-2, a tentative hypothesis of site I energy transduction was proposed.", "contents": "Studies on the mechanism of site I energy conservation. 1. Of the several iron-sulfur centers detected in the site I segment of the respiratory chain, centers N-2 and N-1a alone exhibit apparent phosphate-potential dependent half-reduction potentials, indicating their possible involvement in energy conservation. 2. At high phosphate potential, the apparent half-reduction potential of center N-2 shifts positively by 125 +/- 20 mV, while center N-1a shifts negatively by approximately 60 mV. 3. The redox state of individual iron-sulfur centers in various metabolic states was analyzed. Center N-2 is highly reduced (greater than 90%) in \"state 4\" mitochondria, while center N-1a stays mostly oxidized. 4. In a submitochondrial system, ATP addition induced reduction of center N-2 if the Eh of the suspension was poised from the high potential side of site I using the succinate/fumarate couple. In contrast, center N-2 was oxidized upon energization, if the Eh of the system was poised from the low potential side using the NADH/NAD couple. 5. Based on these redox behaviors of center N-2, a tentative hypothesis of site I energy transduction was proposed."} {"id": "PMID:179812", "title": "Preparation and properties of 3-halopyridine--adenine dinucleotides, NAD+ analogues and model compounds.", "content": "The preparation of model compounds 1-(2',6'-dichlorobenzyl)-3-halogenopyridinium and the study of their properties were achieved. Their chemical reduction to the corresponding 1,4-dihydropyridines is proved by spectroscopic analysis. 3-Iodopyridine--adenine dinucleotide was prepared by enzymic transglycosidation while the 3-chloro, 3-bromo and 3-iodo pyridine--adenine dinucleotides were synthesized from 3-amino-pyridine--adenine dinucleotide. The 3-halogenopyridine--adenine dinucleotides were proved to be active as hydrogen acceptors with alcohol as a substrate. The absorption band at 290 nm of cinnamaldehyde appeared to be a very sensitive tool for studying the enzymic reaction. With the alcohol dehydrogenase from yeast, only slight activity was detected. 3-Halogenopyridine--adenine dinucleotides are competitive inhibitors with respect to nicotinamide--adenine dinucleotide with alcohol dehydrogenase from yeast, lactate dehydrogenase and malate dehydrogenase. The use of 3-iodopyridine--adenine dinucleotide as a heavy-atom derivative for X-ray structure determination is proposed.", "contents": "Preparation and properties of 3-halopyridine--adenine dinucleotides, NAD+ analogues and model compounds. The preparation of model compounds 1-(2',6'-dichlorobenzyl)-3-halogenopyridinium and the study of their properties were achieved. Their chemical reduction to the corresponding 1,4-dihydropyridines is proved by spectroscopic analysis. 3-Iodopyridine--adenine dinucleotide was prepared by enzymic transglycosidation while the 3-chloro, 3-bromo and 3-iodo pyridine--adenine dinucleotides were synthesized from 3-amino-pyridine--adenine dinucleotide. The 3-halogenopyridine--adenine dinucleotides were proved to be active as hydrogen acceptors with alcohol as a substrate. The absorption band at 290 nm of cinnamaldehyde appeared to be a very sensitive tool for studying the enzymic reaction. With the alcohol dehydrogenase from yeast, only slight activity was detected. 3-Halogenopyridine--adenine dinucleotides are competitive inhibitors with respect to nicotinamide--adenine dinucleotide with alcohol dehydrogenase from yeast, lactate dehydrogenase and malate dehydrogenase. The use of 3-iodopyridine--adenine dinucleotide as a heavy-atom derivative for X-ray structure determination is proposed."} {"id": "PMID:179813", "title": "Metallocytochromes c: characterization of electronic absorption and emission spectra of Sn4+ and Zn2+ cytochromes c.", "content": "Tin (Sn4+) and zinc (Zn2+) derivatives of horse heart cytochrome c have been prepared and their optical spectra have been characterized. Zinc cytochrome c has visible absorption maxima at 549 and 585 nm and Soret absorption at 423 nm. Tin cytochrome c shows visible absorption maxima at 536 and 574 nm and Soret absorption at 410 nm. Unlike iron cytochrome c in which the emission spectrum of the porphyrin is almost completely quenched by the central metal, the zinc and tin derivatives of cytochrome c are both fluorescent and phosphorescent. The fluorescence maxima of zinc cytochrome c are at 590 and 640 nm and the fluorescence lifetime is 3.2 ns. The fluorescence maxima of Sn cytochrome are at 580 and 636 nm and the fluorescence lifetime is under 1 ns. The quantum yield of fluorescence is Zn greater than Sn while the quantum yield of phosphorescence is Sn greater than Zn. at 77 K the fluorescence and phosphorescence emission spectra of Sn and Zn cytochrome c show evidence of resolution into vibrational bands. The best resolved bands occur at frequency differences 750 cm-1 and 1540--1550 cm-1 from the O-O transition. These frequencies correspond with those obtained by resonance Raman spectroscopy for in-plane deformations of the porphyrin macrocycle.", "contents": "Metallocytochromes c: characterization of electronic absorption and emission spectra of Sn4+ and Zn2+ cytochromes c. Tin (Sn4+) and zinc (Zn2+) derivatives of horse heart cytochrome c have been prepared and their optical spectra have been characterized. Zinc cytochrome c has visible absorption maxima at 549 and 585 nm and Soret absorption at 423 nm. Tin cytochrome c shows visible absorption maxima at 536 and 574 nm and Soret absorption at 410 nm. Unlike iron cytochrome c in which the emission spectrum of the porphyrin is almost completely quenched by the central metal, the zinc and tin derivatives of cytochrome c are both fluorescent and phosphorescent. The fluorescence maxima of zinc cytochrome c are at 590 and 640 nm and the fluorescence lifetime is 3.2 ns. The fluorescence maxima of Sn cytochrome are at 580 and 636 nm and the fluorescence lifetime is under 1 ns. The quantum yield of fluorescence is Zn greater than Sn while the quantum yield of phosphorescence is Sn greater than Zn. at 77 K the fluorescence and phosphorescence emission spectra of Sn and Zn cytochrome c show evidence of resolution into vibrational bands. The best resolved bands occur at frequency differences 750 cm-1 and 1540--1550 cm-1 from the O-O transition. These frequencies correspond with those obtained by resonance Raman spectroscopy for in-plane deformations of the porphyrin macrocycle."} {"id": "PMID:179814", "title": "Specific interactions of 3-phosphoglyceroyl-glyceraldehyde-3-phosphate dehydrogenase with coenzymes.", "content": "The binding of oxidized and reduced coenzyme (NAD+ and NADH) to 3-phosphoglyceroyl-glyceraldehyde-3-phosphate dehydrogenase has been studied spectrophotometrically and fluorimetrically. The binding of NAD+ to the acylated sturgeon enzyme is characterized by a significant quenching of the enzyme fluorescence (about 25%) and the induction of a difference spectrum in the ultraviolet absorbance region of the enzyme. Both of these spectroscopic properties are quantitatively distinguishable from those of the corresponding binary enzyme-NAD+ complex. Binding isotherms estimated by gel filtration of the acylated enzyme are in close agreement to those obtained by spectrophotometric and fluorimetric titrations. Up to four NAD+ molecules are bound to the enzyme tetramer. No anticooperativity can be detected in the binding of oxidized coenzyme, which is well described on the basis of a single class of four binding sites with a dissociation constant of 25 muM at 10 degrees C, pH 7.0. The binding of NADH to the acylenzyme has been characterized spectrophotometrically. The absorption band of the dihydronicotinamide moiety of the coenzyme is blue-shifted to 335 nm with respect to free NADH. In addition, a large hypochromicity (23%) is observed together with a significant increase of the bandwidth at half height of this absorption band. This last property is specific to the acylenzyme-DADH complex, since it disappears upon arsenolysis of the acylenzyme. The binding affinity of NADH to the acylated enzyme has been estimated by performing simultaneous spectrophotometric and fluorimetric titrations of the NADH appearance upon addition of NAD+ to a mixture of enzyme and excess glyceraldehyde 3-phosphate. In contrast to NAD+, the reduced coenzyme NADH appears to be relatively strongly bound to the acylated enzyme, the dissociation constant of the acylenzyme-NADH complex being estimated as 2.0 muM at 25 degrees C. In addition a large quenching of the NADH fluorescence (about 83%) is observed. The comparison of the dissociation constants of the coenzyme-acylenzyme complexes and the corresponding Michaelis constants suggests a reaction mechanism of the enzyme in which significant formation and dissociation of NAD+-acylenzyme and NADH-acylenzyme complexes occur. Under physiological conditions the activity of the enzyme can be regulated by the ratio of oxidized and reduced coenzymes. Possible reasons for the lack of anticooperativity in coenzyme binding to the acylated form of the enzyme are discussed.", "contents": "Specific interactions of 3-phosphoglyceroyl-glyceraldehyde-3-phosphate dehydrogenase with coenzymes. The binding of oxidized and reduced coenzyme (NAD+ and NADH) to 3-phosphoglyceroyl-glyceraldehyde-3-phosphate dehydrogenase has been studied spectrophotometrically and fluorimetrically. The binding of NAD+ to the acylated sturgeon enzyme is characterized by a significant quenching of the enzyme fluorescence (about 25%) and the induction of a difference spectrum in the ultraviolet absorbance region of the enzyme. Both of these spectroscopic properties are quantitatively distinguishable from those of the corresponding binary enzyme-NAD+ complex. Binding isotherms estimated by gel filtration of the acylated enzyme are in close agreement to those obtained by spectrophotometric and fluorimetric titrations. Up to four NAD+ molecules are bound to the enzyme tetramer. No anticooperativity can be detected in the binding of oxidized coenzyme, which is well described on the basis of a single class of four binding sites with a dissociation constant of 25 muM at 10 degrees C, pH 7.0. The binding of NADH to the acylenzyme has been characterized spectrophotometrically. The absorption band of the dihydronicotinamide moiety of the coenzyme is blue-shifted to 335 nm with respect to free NADH. In addition, a large hypochromicity (23%) is observed together with a significant increase of the bandwidth at half height of this absorption band. This last property is specific to the acylenzyme-DADH complex, since it disappears upon arsenolysis of the acylenzyme. The binding affinity of NADH to the acylated enzyme has been estimated by performing simultaneous spectrophotometric and fluorimetric titrations of the NADH appearance upon addition of NAD+ to a mixture of enzyme and excess glyceraldehyde 3-phosphate. In contrast to NAD+, the reduced coenzyme NADH appears to be relatively strongly bound to the acylated enzyme, the dissociation constant of the acylenzyme-NADH complex being estimated as 2.0 muM at 25 degrees C. In addition a large quenching of the NADH fluorescence (about 83%) is observed. The comparison of the dissociation constants of the coenzyme-acylenzyme complexes and the corresponding Michaelis constants suggests a reaction mechanism of the enzyme in which significant formation and dissociation of NAD+-acylenzyme and NADH-acylenzyme complexes occur. Under physiological conditions the activity of the enzyme can be regulated by the ratio of oxidized and reduced coenzymes. Possible reasons for the lack of anticooperativity in coenzyme binding to the acylated form of the enzyme are discussed."} {"id": "PMID:179815", "title": "Interaction of apoprotein from porcine high-density lipoprotein with dimyristoyl lecithin. 1. The structure of the complexes.", "content": "The morphology and structural organisation of the complexes formed from the apoprotein of porcine high-density lipoprotein and dimyristoyl phosphatidylcholine (lecithin) have been studied using the technique of small-angle X-ray scattering. Scattering measurements made in solvents of varying electron density were interpreted in terms of a scattering-equivalent model for the structure of the complex. This model is described by an oblate ellipsoidal morphology with dimensions at 20 degrees C: major axis 11.0 nm, minor axis 5.5 nm. Within this overall shape the lipid hydrocarbon chains are organised in an apolar core whilst the lipid polar head groups and protein are located in a outer shell 0.85 nm in thickness. The oblate morphology demonstrates that the structure of the complex is directed by the fundamental bilayer organisation of the lecithin. The dimension of the minor axis (5.5 nm) indicates that phospholipid hydrocarbon chains are orientated perpendicular to the interface.", "contents": "Interaction of apoprotein from porcine high-density lipoprotein with dimyristoyl lecithin. 1. The structure of the complexes. The morphology and structural organisation of the complexes formed from the apoprotein of porcine high-density lipoprotein and dimyristoyl phosphatidylcholine (lecithin) have been studied using the technique of small-angle X-ray scattering. Scattering measurements made in solvents of varying electron density were interpreted in terms of a scattering-equivalent model for the structure of the complex. This model is described by an oblate ellipsoidal morphology with dimensions at 20 degrees C: major axis 11.0 nm, minor axis 5.5 nm. Within this overall shape the lipid hydrocarbon chains are organised in an apolar core whilst the lipid polar head groups and protein are located in a outer shell 0.85 nm in thickness. The oblate morphology demonstrates that the structure of the complex is directed by the fundamental bilayer organisation of the lecithin. The dimension of the minor axis (5.5 nm) indicates that phospholipid hydrocarbon chains are orientated perpendicular to the interface."} {"id": "PMID:179816", "title": "Interaction of apoprotein from porcine high-density lipoprotein with dimyristoly lecithin. 2. Nature of lipid-protein interaction.", "content": "The detailed molecular structure of the complex formed by the apoprotein from porcine high density lipoprotein and dimyristoly phosphatidylcholine (lecithin) has been investigated by a range of physical techniques. The complex, an oblate ellipsoid with major axis 11.0 nm and minor axis 5.5 nm (see the accompanying paper), is comprised of a section of lecithin bilayer with apoprotein at the surface. The main site of interaction between protein and lipid is in the lipid glycerophosphorylcholine group region; as with native high density lipoprotein the surface of the particle consists of a mosaic of lecithin polar groups and protein. The formation of this mosaic reduces the cooperativity of the lecithin chain motions and changes the curvature of the lipid-water interface, as compared to a bilayer. Otherwise, there are no major changes in lecithin motions indicating that no strong binding of lipid to protein occurs. The interaction involves the intercalation of amphipathic, 60% alpha-helical, apoprotein molecules among the lecithin molecules so that the protein residues at the lipid-water interface. The apoprotein has a high affinity for the lipid-water interface but specific lipid-protein interactions are not involved.", "contents": "Interaction of apoprotein from porcine high-density lipoprotein with dimyristoly lecithin. 2. Nature of lipid-protein interaction. The detailed molecular structure of the complex formed by the apoprotein from porcine high density lipoprotein and dimyristoly phosphatidylcholine (lecithin) has been investigated by a range of physical techniques. The complex, an oblate ellipsoid with major axis 11.0 nm and minor axis 5.5 nm (see the accompanying paper), is comprised of a section of lecithin bilayer with apoprotein at the surface. The main site of interaction between protein and lipid is in the lipid glycerophosphorylcholine group region; as with native high density lipoprotein the surface of the particle consists of a mosaic of lecithin polar groups and protein. The formation of this mosaic reduces the cooperativity of the lecithin chain motions and changes the curvature of the lipid-water interface, as compared to a bilayer. Otherwise, there are no major changes in lecithin motions indicating that no strong binding of lipid to protein occurs. The interaction involves the intercalation of amphipathic, 60% alpha-helical, apoprotein molecules among the lecithin molecules so that the protein residues at the lipid-water interface. The apoprotein has a high affinity for the lipid-water interface but specific lipid-protein interactions are not involved."} {"id": "PMID:179817", "title": "Properties of enzyme fraction A from Chlorella and copurification of 3' (2'), 5'-biphosphonucleoside 3' (2')-phosphohydrolase, adenosine 5'phosphosulfate sulfohydrolase and adenosine-5'-phosphosulfate cyclase activities.", "content": "Enzyme fraction A from Chlorella which catalyzes the formation of adenosine 5'-phosphosulfate from adenosine 3'-phosphate 5'-phosphosulfate is further characterized. Fraction A is found to contain an Mg2+ -activated and Ca2+ -inhibited 3' (2')-nucleotidase specific for 3' (2'), 5'-biphosphonucleosides. This activity has been named 3' (2), 5'-biphosphonucleoside 3' (2')-phosphohydrolase. The A fraction is also found to contain an activity which catalyzes the formation of adenosine 3':5'-monophosphate (cyclic AMP) from adenosine 5'-phosphosulfate (adenosine 5'-phosphosulfate cyclase). Under the same conditions of assay, 5'-ATP and 5'-ADP are not substrated for cyclic AMP formation. Unlike the 3' (2'), 5'-biphosphonucleoside 3' (2')-phosphohydrolase activity, the adenosine 5'-phosphosulfate cyclase activity does not require Mg2+, requires NH+4 or Na+, and is not inhibited by Ca2+. The A fraction also contains an adenosine 5'-phospho sulfate sulfohydrolase activity which forms 5'-AMP and sulfate. The three activities remain together during purification and acrylamide gel electrophoresis of the purified preparation yields a pattern where only one protein band has all three activities. The phosphohydrolase can be separated from the other two activities by affinity chromatography on agarose-hexyl-adenosine 3'n5'-bisphosphate yielding a phosphohydrolase preparation showing a single band on gel electrophoresis. The adenosine 5'-phosphosulfate cyclase may provide an alternate route of cyclic AMP formation from sulfate via ATP sulfurylase, but its regulatory significance in Chlorella, if any, remains to be demonstrated. In sulfate reduction, the phosphohydrolase may serve to provide a readily utilized pool of adenosine 5'-phosphosulfate as needed by the adenosine 5'-phosphosulfate sulfotransferase. The cyclase and sulfohydrolase activities would be regarded as side reactions incidental to this pathway, but may be of importance in other metabolic and regulatory reactions.", "contents": "Properties of enzyme fraction A from Chlorella and copurification of 3' (2'), 5'-biphosphonucleoside 3' (2')-phosphohydrolase, adenosine 5'phosphosulfate sulfohydrolase and adenosine-5'-phosphosulfate cyclase activities. Enzyme fraction A from Chlorella which catalyzes the formation of adenosine 5'-phosphosulfate from adenosine 3'-phosphate 5'-phosphosulfate is further characterized. Fraction A is found to contain an Mg2+ -activated and Ca2+ -inhibited 3' (2')-nucleotidase specific for 3' (2'), 5'-biphosphonucleosides. This activity has been named 3' (2), 5'-biphosphonucleoside 3' (2')-phosphohydrolase. The A fraction is also found to contain an activity which catalyzes the formation of adenosine 3':5'-monophosphate (cyclic AMP) from adenosine 5'-phosphosulfate (adenosine 5'-phosphosulfate cyclase). Under the same conditions of assay, 5'-ATP and 5'-ADP are not substrated for cyclic AMP formation. Unlike the 3' (2'), 5'-biphosphonucleoside 3' (2')-phosphohydrolase activity, the adenosine 5'-phosphosulfate cyclase activity does not require Mg2+, requires NH+4 or Na+, and is not inhibited by Ca2+. The A fraction also contains an adenosine 5'-phospho sulfate sulfohydrolase activity which forms 5'-AMP and sulfate. The three activities remain together during purification and acrylamide gel electrophoresis of the purified preparation yields a pattern where only one protein band has all three activities. The phosphohydrolase can be separated from the other two activities by affinity chromatography on agarose-hexyl-adenosine 3'n5'-bisphosphate yielding a phosphohydrolase preparation showing a single band on gel electrophoresis. The adenosine 5'-phosphosulfate cyclase may provide an alternate route of cyclic AMP formation from sulfate via ATP sulfurylase, but its regulatory significance in Chlorella, if any, remains to be demonstrated. In sulfate reduction, the phosphohydrolase may serve to provide a readily utilized pool of adenosine 5'-phosphosulfate as needed by the adenosine 5'-phosphosulfate sulfotransferase. The cyclase and sulfohydrolase activities would be regarded as side reactions incidental to this pathway, but may be of importance in other metabolic and regulatory reactions."} {"id": "PMID:179818", "title": "Arginyl-tRNA synthetase from baker's yeast. Purification and some properties.", "content": "Arginyl-tRNA synthetase from baker's yeast (Saccharomyces cerevisiae, strain 836) was obtained pure by a large-scale preparative method, which involves four chromatographic columns and one preparative polyacrylamide gel electrophoretic step. The enzyme has a high specific activity (9000 U/mg) and consists of a single polypeptide chain of molecular weight approximately 73000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Amino acid analysis of the enzyme permitted calculation of the absorption coefficient of arginyl-tRNA synthetase (A(1 mg/ml 280 nm)=1.26). Concerning kinetic parameters of the enzyme we found the following Km values: 0.28 muM, 300 muM, 1.5 muM for tRNA(Arg III), ATP and arginine in the aminoacylation reaction, and 1400 muM, 2.5 muM, and 50 muM for ATP, arginine and PP(i) in the ATP-PP(i) exchange reaction. Arginyl-tRNA synthetase required tRNA(Arg III) to catalyse the ATP-PP(i) exchange reaction.", "contents": "Arginyl-tRNA synthetase from baker's yeast. Purification and some properties. Arginyl-tRNA synthetase from baker's yeast (Saccharomyces cerevisiae, strain 836) was obtained pure by a large-scale preparative method, which involves four chromatographic columns and one preparative polyacrylamide gel electrophoretic step. The enzyme has a high specific activity (9000 U/mg) and consists of a single polypeptide chain of molecular weight approximately 73000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Amino acid analysis of the enzyme permitted calculation of the absorption coefficient of arginyl-tRNA synthetase (A(1 mg/ml 280 nm)=1.26). Concerning kinetic parameters of the enzyme we found the following Km values: 0.28 muM, 300 muM, 1.5 muM for tRNA(Arg III), ATP and arginine in the aminoacylation reaction, and 1400 muM, 2.5 muM, and 50 muM for ATP, arginine and PP(i) in the ATP-PP(i) exchange reaction. Arginyl-tRNA synthetase required tRNA(Arg III) to catalyse the ATP-PP(i) exchange reaction."} {"id": "PMID:179819", "title": "Electron-spin-resonance studies of a chlorpromazine derivative bound to DNA fibres.", "content": "Solutions of DNA, spin-labelled with the radical cation of chlorpromazine, were used to produce oriented species of fibres pulled from a gel obtained by ultracentrifugation. The electron spin resonance spectra, recorded at X and Q band frequencies, are given for both gel and fibres; 14N hyperfine coupling parameters were obtained by computer fitting. The spectra are explained in terms of a strongly immobilized label having one principal hyperfine tensor axis parallel to the axis of the DNA helix, and the preferential orientation of the chlorpromazine ions with their planes perpendicular to the DNA helical axis.", "contents": "Electron-spin-resonance studies of a chlorpromazine derivative bound to DNA fibres. Solutions of DNA, spin-labelled with the radical cation of chlorpromazine, were used to produce oriented species of fibres pulled from a gel obtained by ultracentrifugation. The electron spin resonance spectra, recorded at X and Q band frequencies, are given for both gel and fibres; 14N hyperfine coupling parameters were obtained by computer fitting. The spectra are explained in terms of a strongly immobilized label having one principal hyperfine tensor axis parallel to the axis of the DNA helix, and the preferential orientation of the chlorpromazine ions with their planes perpendicular to the DNA helical axis."} {"id": "PMID:179820", "title": "Partial purification and some properties of oxalacetase from Aspergillus niger.", "content": "1. Oxalacetase from Asperigillus niger was found to be an inducible enzyme, the induction being dependent not only on neutralisation of the acidic growth medium but also on the presence of carbonate. An explanation is proposed. 2. Three methods were established for the quantitative determination of oxalacetase activity. These are based on the determination of the product acetate, on the absorbance of oxaloacetate and on coupling the hydrolysis of oxaloacetate to the oxidation of malate by NAD in the presence of malate dehydrogenase. 3. Oxalacetase was purified about 50-fold from cell-free extracts of A. niger and used to determine some of its properties such as kinetic constants. 4. 2S-[U-14C, 3-2H2] Malate in the presence of oxalacetase, NAD and malate dehydrogenase was partially converted to acetate and oxalate. The 3H/14C ratio of the isolated acetate was nearly twice as high as that of the malate used initially. The result demonstrates that the keto form of oxaloacetate, not the enol, is the substrate of the enzyme. 5. Equimolecular mixtures of 2S, 3S-[3-2H1] malate + 2S-[2-2H1] malate (mixture 1) and 2S, 3R-[3-2H1, 3H1] malate + 2S, 3R-[2-2H1, 3-3H1] malate (mixture 2) were prepared from 2S-[3-3H2] malate by incubation with fumarase in normal and tritiated water, respectively. The isolated mixture 1, in the presence of oxalacetase, NAD and malate dehydrogenase was incubated in tritiated water for formation of acetate and oxalate; the isolated mixture 2 was treated likewise in normal water. 6. The mixtures of symmetrically labelled [3H1] acetate and chiral acetates thus produced were isolated and the configuration of the [3H1, 3H1] acetate specimens was determined in the sequence acetate leads to malate leads to fumarate, as usual. The [2H1, 3H1] acetate derived from 2S, 3S-[3-2H1] malate (present in mixture 1( yielded a malate which on incubation with fumarase retained 65.0% of its total tritium content. This chiral acetate, therefore, had the R configuration. The [2H1, 3H1] acetate derived from 2S, 3R-[2-2H1, 3-3H1] malate produced a malate which retained 35% of its total tritium content, and therefore had the S configuration. 7. It was concluded that the detachment of the oxaloyl residue from oxaloacetate and its replacement by a proton proceed with inversion of configuration at the methylene group which becomes methyl during the hydrolysis.", "contents": "Partial purification and some properties of oxalacetase from Aspergillus niger. 1. Oxalacetase from Asperigillus niger was found to be an inducible enzyme, the induction being dependent not only on neutralisation of the acidic growth medium but also on the presence of carbonate. An explanation is proposed. 2. Three methods were established for the quantitative determination of oxalacetase activity. These are based on the determination of the product acetate, on the absorbance of oxaloacetate and on coupling the hydrolysis of oxaloacetate to the oxidation of malate by NAD in the presence of malate dehydrogenase. 3. Oxalacetase was purified about 50-fold from cell-free extracts of A. niger and used to determine some of its properties such as kinetic constants. 4. 2S-[U-14C, 3-2H2] Malate in the presence of oxalacetase, NAD and malate dehydrogenase was partially converted to acetate and oxalate. The 3H/14C ratio of the isolated acetate was nearly twice as high as that of the malate used initially. The result demonstrates that the keto form of oxaloacetate, not the enol, is the substrate of the enzyme. 5. Equimolecular mixtures of 2S, 3S-[3-2H1] malate + 2S-[2-2H1] malate (mixture 1) and 2S, 3R-[3-2H1, 3H1] malate + 2S, 3R-[2-2H1, 3-3H1] malate (mixture 2) were prepared from 2S-[3-3H2] malate by incubation with fumarase in normal and tritiated water, respectively. The isolated mixture 1, in the presence of oxalacetase, NAD and malate dehydrogenase was incubated in tritiated water for formation of acetate and oxalate; the isolated mixture 2 was treated likewise in normal water. 6. The mixtures of symmetrically labelled [3H1] acetate and chiral acetates thus produced were isolated and the configuration of the [3H1, 3H1] acetate specimens was determined in the sequence acetate leads to malate leads to fumarate, as usual. The [2H1, 3H1] acetate derived from 2S, 3S-[3-2H1] malate (present in mixture 1( yielded a malate which on incubation with fumarase retained 65.0% of its total tritium content. This chiral acetate, therefore, had the R configuration. The [2H1, 3H1] acetate derived from 2S, 3R-[2-2H1, 3-3H1] malate produced a malate which retained 35% of its total tritium content, and therefore had the S configuration. 7. It was concluded that the detachment of the oxaloyl residue from oxaloacetate and its replacement by a proton proceed with inversion of configuration at the methylene group which becomes methyl during the hydrolysis."} {"id": "PMID:179821", "title": "The cytochrome bc1 complex of yeast mitochondria. Isolation and partial characterization of the cytochrome bc1 complex and cytochrome b.", "content": "We have isolated the cytochrome bc1 complex and some of its constituent polypeptides from bakers yeast and have studied its spectroscopy, electrophoresis and amino acid analysis. The isolated complex contained 6 mumol of b heme and approximately 3 mumol of c1 heme per g of protein. The electron paramagnetic resonance spectrum was similar to that of the beef-heart preparation. The complex consisted of 7 polypeptides with mobilities on sodium dodecylsulphate polyacrylamide gel electrophoresis corresponding to Mr 44,000, 40,000, 32,000, 32,000, 17,000, 14,000 and 11,000. One of the polypeptides with Mr 32,000 was identified on sodium dodecylsulphate gels as cytochrome c1 by porphyrin fluorescence. Cytochrome b was isolated from the complex by treating it with guanidine hydrochloride; it had a purity of 20 mumol per g of protein and consisted of a polypeptide with Mr 32,000 plus two minor bands with Mr 14,000 and 11,000. We have isolated the polypeptide of Mr 32,000 from cytochrome b and the polypeptides of Mr 44,000 and 40,000 (\"core proteins\") from the complex, both by preparative sodium dodecylsulphate gel electrophoresis and determined their amino acid composition. Only the b polypeptide of Mr 32,000 shows the low proportion of polar amino acid residues that is considered typical of membrane proteins.", "contents": "The cytochrome bc1 complex of yeast mitochondria. Isolation and partial characterization of the cytochrome bc1 complex and cytochrome b. We have isolated the cytochrome bc1 complex and some of its constituent polypeptides from bakers yeast and have studied its spectroscopy, electrophoresis and amino acid analysis. The isolated complex contained 6 mumol of b heme and approximately 3 mumol of c1 heme per g of protein. The electron paramagnetic resonance spectrum was similar to that of the beef-heart preparation. The complex consisted of 7 polypeptides with mobilities on sodium dodecylsulphate polyacrylamide gel electrophoresis corresponding to Mr 44,000, 40,000, 32,000, 32,000, 17,000, 14,000 and 11,000. One of the polypeptides with Mr 32,000 was identified on sodium dodecylsulphate gels as cytochrome c1 by porphyrin fluorescence. Cytochrome b was isolated from the complex by treating it with guanidine hydrochloride; it had a purity of 20 mumol per g of protein and consisted of a polypeptide with Mr 32,000 plus two minor bands with Mr 14,000 and 11,000. We have isolated the polypeptide of Mr 32,000 from cytochrome b and the polypeptides of Mr 44,000 and 40,000 (\"core proteins\") from the complex, both by preparative sodium dodecylsulphate gel electrophoresis and determined their amino acid composition. Only the b polypeptide of Mr 32,000 shows the low proportion of polar amino acid residues that is considered typical of membrane proteins."} {"id": "PMID:179822", "title": "Cushing's syndrome or obesity. Bilateral adrenal hyperplasia in a boy 10 years of age.", "content": "A rare case of the Cushing syndrome, due to bilateral adrenal hyperplasia is described. Because of generalized obesity, normal height, normal bone age and family history of obesity, a boy 10 years of age had at first been misdiagnosed as simple obesity. A reduction in height velocity, advancement of bone age and development of precocious pseudopuberty led to a more detailed biochemical investigation and to the correct diagnosis. The clinical picture can be misleading in the differential diagnosis of Cushing's disease versus simple obesity. From a comparison of reports on pediatric Cushing's syndrome, it is obvious that in most pediatric cases fat distribution differs from that of adult Cushing's syndromes. Stunted growth is reported to be more frequent, but normal and excessive height in Cushing's syndrome is not uncommon. In adrenal hyperplasia a retardation of bone age is usually expected. Interpretation of endocrine functions must take into account that simple obesity leads to secondary endocrinopathies, which are similar to the findings in Cushing's syndromes. Plasma cortisol at midnight and 12 hourly excretion of free cortisol in urine as well as overnight Dexamethasone suppression of morning plasma cortisol are judged to be good screening parameters. Plasma ACTH assays can help in the initial diagnosis and are mandatory during the follow up for an early detection of Nelson's syndrome.", "contents": "Cushing's syndrome or obesity. Bilateral adrenal hyperplasia in a boy 10 years of age. A rare case of the Cushing syndrome, due to bilateral adrenal hyperplasia is described. Because of generalized obesity, normal height, normal bone age and family history of obesity, a boy 10 years of age had at first been misdiagnosed as simple obesity. A reduction in height velocity, advancement of bone age and development of precocious pseudopuberty led to a more detailed biochemical investigation and to the correct diagnosis. The clinical picture can be misleading in the differential diagnosis of Cushing's disease versus simple obesity. From a comparison of reports on pediatric Cushing's syndrome, it is obvious that in most pediatric cases fat distribution differs from that of adult Cushing's syndromes. Stunted growth is reported to be more frequent, but normal and excessive height in Cushing's syndrome is not uncommon. In adrenal hyperplasia a retardation of bone age is usually expected. Interpretation of endocrine functions must take into account that simple obesity leads to secondary endocrinopathies, which are similar to the findings in Cushing's syndromes. Plasma cortisol at midnight and 12 hourly excretion of free cortisol in urine as well as overnight Dexamethasone suppression of morning plasma cortisol are judged to be good screening parameters. Plasma ACTH assays can help in the initial diagnosis and are mandatory during the follow up for an early detection of Nelson's syndrome."} {"id": "PMID:179823", "title": "Intrathecal cytostatic chemotherapy of meningitis carcinomatosa. Clinical manifestation and cerebrospinal fluid cytology in a case of metastatic carcinoma of the breast.", "content": "Effects of intrathecal cytostatic chemotherapy on the clinical symptoms and cerebrospinal fluid (CSF) findings are being demonstrated in a case of metastatic carcinoma of the breast with sighns of meningeal irritation and cranial nerve involvement. Clinical symptoms disappeared after repeated intrathecal applications of methotrexate. CSF cell counts were reverted to normal but tumor cells were found to be persistant in CSF over a period of 19 months. Risks of combined intrathecal and systemic cytostatic therapy and possible effects of parenteral citrovorum factor applications are being discussed. The importance of continued intrathecal chemotherapy and of regular and thorough examination of CSF cells in meningitis carcinomatosa is emphasized. Cytological methods included investigations on viable CSF cells.", "contents": "Intrathecal cytostatic chemotherapy of meningitis carcinomatosa. Clinical manifestation and cerebrospinal fluid cytology in a case of metastatic carcinoma of the breast. Effects of intrathecal cytostatic chemotherapy on the clinical symptoms and cerebrospinal fluid (CSF) findings are being demonstrated in a case of metastatic carcinoma of the breast with sighns of meningeal irritation and cranial nerve involvement. Clinical symptoms disappeared after repeated intrathecal applications of methotrexate. CSF cell counts were reverted to normal but tumor cells were found to be persistant in CSF over a period of 19 months. Risks of combined intrathecal and systemic cytostatic therapy and possible effects of parenteral citrovorum factor applications are being discussed. The importance of continued intrathecal chemotherapy and of regular and thorough examination of CSF cells in meningitis carcinomatosa is emphasized. Cytological methods included investigations on viable CSF cells."} {"id": "PMID:179824", "title": "Positive chronotropic effect of dialysable peptides derived from plasmin digestion of bovine fibrinogen preparations.", "content": "Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon.", "contents": "Positive chronotropic effect of dialysable peptides derived from plasmin digestion of bovine fibrinogen preparations. Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon."} {"id": "PMID:179825", "title": "Biochemical and mechanical effects of phenylephrine on the heart.", "content": "Injections of phenylephrine into isolated perfused guinea pig hearts increased cyclic AMP and phosphorylase a. Reserpine pretreatment or propranolol decreased or abolished the phenylephrine-induced biochemical changes without affecting the contractile response. Phentolamine, on the other hand, shifted the phenylephrine dose-response curve for contractility to the right without affecting the other parameters. The biochemical effects of phenylephrine are apparently due to the release of noradrenaline while the contractile effect is mediated directly through stimulation of alpha-adrenoceptors.", "contents": "Biochemical and mechanical effects of phenylephrine on the heart. Injections of phenylephrine into isolated perfused guinea pig hearts increased cyclic AMP and phosphorylase a. Reserpine pretreatment or propranolol decreased or abolished the phenylephrine-induced biochemical changes without affecting the contractile response. Phentolamine, on the other hand, shifted the phenylephrine dose-response curve for contractility to the right without affecting the other parameters. The biochemical effects of phenylephrine are apparently due to the release of noradrenaline while the contractile effect is mediated directly through stimulation of alpha-adrenoceptors."} {"id": "PMID:179826", "title": "A noradren aline sensitive adenylate cyclase in the rat limbic forebrain: preparation, properties and the effects of agonists, adrenolytics and neuroleptic drugs.", "content": "A method for the preparation of a noradrenaline sensitive adenylate cyclase from homogenates of the rat 'limbic' forebrain is described using Krebs--Ringer as the homogenising medium. Some of its properties resemble those reported previously by other workers, using slices. Its response to agonists show that it has the characteristics of a beta1-receptor i.e. the potency of 1-isoprenaline exceeds that of 1-noradrenaline which exceeds that of 1-adrenaline. Structure--activity analysis of the response of the adenylate cyclase to a range of adrenergic agonists shows a strict requirement for a catechol moiety and a beta-hydroxyl group. The activation of the enzyme by 1-noradrenaline is sensitive to stereoselective inhibition by 1-propranolol. The effect of a number of neuroleptic drugs was examined. Promazine was the most effective agent tested in antagonising the stimulation produced by 50 muM 1-noradrenaline, whilst the potent dopamine receptor antagonist, alpha-flupenthixol was only weakly active. Furthermore, there was no stereoselectivity in the antagonism produced by alpha- and beta-siomers of flupenthixol. Pimozide was not found to be a potent antagonist. Thus the spectrum of antagonism produced by neuroleptic drugs was quite different from that seen in the dopamine sensitive adenylate cyclase of the rat corpus striatum.", "contents": "A noradren aline sensitive adenylate cyclase in the rat limbic forebrain: preparation, properties and the effects of agonists, adrenolytics and neuroleptic drugs. A method for the preparation of a noradrenaline sensitive adenylate cyclase from homogenates of the rat 'limbic' forebrain is described using Krebs--Ringer as the homogenising medium. Some of its properties resemble those reported previously by other workers, using slices. Its response to agonists show that it has the characteristics of a beta1-receptor i.e. the potency of 1-isoprenaline exceeds that of 1-noradrenaline which exceeds that of 1-adrenaline. Structure--activity analysis of the response of the adenylate cyclase to a range of adrenergic agonists shows a strict requirement for a catechol moiety and a beta-hydroxyl group. The activation of the enzyme by 1-noradrenaline is sensitive to stereoselective inhibition by 1-propranolol. The effect of a number of neuroleptic drugs was examined. Promazine was the most effective agent tested in antagonising the stimulation produced by 50 muM 1-noradrenaline, whilst the potent dopamine receptor antagonist, alpha-flupenthixol was only weakly active. Furthermore, there was no stereoselectivity in the antagonism produced by alpha- and beta-siomers of flupenthixol. Pimozide was not found to be a potent antagonist. Thus the spectrum of antagonism produced by neuroleptic drugs was quite different from that seen in the dopamine sensitive adenylate cyclase of the rat corpus striatum."} {"id": "PMID:179827", "title": "Alterations in splanchnic cyclic nucleotide levels in splanchnic artery occlusion shock and their modification by dexamethasone.", "content": "The effects of dexamethasone sodium phosphate (DSP), 5 mg/kg, administration on the biochemical alterations in hepatic tissue subsequent to the production os splanchnic artery occlusion (SAO) shock was investigated. Following the induction of SAO shock, DSP-treated dogs exhibited a significantly improved cardiovascular status compared to placebo-treated shocked dogs, 2 hr after release of the occlusion, biopsies of the liver were taken and analyzed for beta-glucuronidase (BG), adenosine-3',5'-cyclic monophosphate (cAMP) and guanosine-3',5'-cyclic monophosphate (cGMP) content. SAO shock produced a significant increase in hepatic free BG activity which was reversed by DSP pretreatment. Additionally, SAO shock decreased hepatic cAMP levels, increased cGMP levels and significantly lowered the hepatic ratio of cAMP/cGMP. These changes in cyclic nucleotide levels were reversed by DSP administration and were found to be inversely related to changes in hepatic free BG activity. Thus, the ratio of cellular cAMP/cGMP may function as a regulatory mechanism for lysosomal enzyme release secondary to ischemia and hypoxia. Further, DSP may act to maintain lysosomal integrity in ischemic tissues by preservation of cAMP/cGMP ratios.", "contents": "Alterations in splanchnic cyclic nucleotide levels in splanchnic artery occlusion shock and their modification by dexamethasone. The effects of dexamethasone sodium phosphate (DSP), 5 mg/kg, administration on the biochemical alterations in hepatic tissue subsequent to the production os splanchnic artery occlusion (SAO) shock was investigated. Following the induction of SAO shock, DSP-treated dogs exhibited a significantly improved cardiovascular status compared to placebo-treated shocked dogs, 2 hr after release of the occlusion, biopsies of the liver were taken and analyzed for beta-glucuronidase (BG), adenosine-3',5'-cyclic monophosphate (cAMP) and guanosine-3',5'-cyclic monophosphate (cGMP) content. SAO shock produced a significant increase in hepatic free BG activity which was reversed by DSP pretreatment. Additionally, SAO shock decreased hepatic cAMP levels, increased cGMP levels and significantly lowered the hepatic ratio of cAMP/cGMP. These changes in cyclic nucleotide levels were reversed by DSP administration and were found to be inversely related to changes in hepatic free BG activity. Thus, the ratio of cellular cAMP/cGMP may function as a regulatory mechanism for lysosomal enzyme release secondary to ischemia and hypoxia. Further, DSP may act to maintain lysosomal integrity in ischemic tissues by preservation of cAMP/cGMP ratios."} {"id": "PMID:179839", "title": "Stimulation of ribonuclease activity and its isoenzymes in germinating seeds of cowpea (Vigna sinensis) by gibberellic acid and adenosine-3',5-cyclic monophosphate.", "content": "Application of GA3 and cyclic AMP to cowpea seedings caused a 2-3 fold stimulation of RNAase activity, together with the augmentation of RNAase isoenzymes. Inhibitor studies indicated the requirement of fresh RNA and protein synthesis for enzyme stimulation.", "contents": "Stimulation of ribonuclease activity and its isoenzymes in germinating seeds of cowpea (Vigna sinensis) by gibberellic acid and adenosine-3',5-cyclic monophosphate. Application of GA3 and cyclic AMP to cowpea seedings caused a 2-3 fold stimulation of RNAase activity, together with the augmentation of RNAase isoenzymes. Inhibitor studies indicated the requirement of fresh RNA and protein synthesis for enzyme stimulation."} {"id": "PMID:179840", "title": "Cytokinin ocntents and cAMP metabolism during growth of Escherchia coli.", "content": "During Escherichia coli growth, we found an inverse correlation between free cytokinin content and cAMP level. The rates of synthesis of adenylate-cyclase and cAMP-phosphodiesterase were practically constant.", "contents": "Cytokinin ocntents and cAMP metabolism during growth of Escherchia coli. During Escherichia coli growth, we found an inverse correlation between free cytokinin content and cAMP level. The rates of synthesis of adenylate-cyclase and cAMP-phosphodiesterase were practically constant."} {"id": "PMID:179841", "title": "Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle.", "content": "The incorporation of leucine-14C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10-3 M) and decreased by cyclic AMP (10-3 M). There was no effect of 5'AMP (10-3 M). The phosphodiesterase inhibiting drugs theophylline (10-3 M) and papaverine (5 x 10-5 g/ml) both decreased the leucine-14C incorporation.", "contents": "Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle. The incorporation of leucine-14C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10-3 M) and decreased by cyclic AMP (10-3 M). There was no effect of 5'AMP (10-3 M). The phosphodiesterase inhibiting drugs theophylline (10-3 M) and papaverine (5 x 10-5 g/ml) both decreased the leucine-14C incorporation."} {"id": "PMID:179842", "title": "Myopathic changes at the end-plate region induced by neostigmine methylsulfate.", "content": "Administration of large dose of neostigmine caused very quickly marked myopathic changes at the motor end-plate region. With continued injections, however, some recovery of the structural features did occur suggesting the reconstructive changes in the affected regions.", "contents": "Myopathic changes at the end-plate region induced by neostigmine methylsulfate. Administration of large dose of neostigmine caused very quickly marked myopathic changes at the motor end-plate region. With continued injections, however, some recovery of the structural features did occur suggesting the reconstructive changes in the affected regions."} {"id": "PMID:179843", "title": "Plasticity of the hormone receptors and possibility of their deformation in neonatal age.", "content": "Gonadotropin or TSH treated newborn animals reacted to TSH treatment in their adult age in a lesser degree than control ones. This suggests the plasticity of hormone receptors and the possibility of their deformation in neonatal age.", "contents": "Plasticity of the hormone receptors and possibility of their deformation in neonatal age. Gonadotropin or TSH treated newborn animals reacted to TSH treatment in their adult age in a lesser degree than control ones. This suggests the plasticity of hormone receptors and the possibility of their deformation in neonatal age."} {"id": "PMID:179844", "title": "Hormonal induction of glutamate dehydrogenase in rat liver.", "content": "Glutamate dehydrogenase rapidly increases in microsomes and appears in the cytoplasm after administration of cortisone, cAMP, hydrocortisone-acetate. Prolonged administration of ACTH maintains high level of enzyme in the mitochondria and microsomes. Hydrocortisone-acetate, insulin and cortisone decrease drastically enzyme in mitochondria.", "contents": "Hormonal induction of glutamate dehydrogenase in rat liver. Glutamate dehydrogenase rapidly increases in microsomes and appears in the cytoplasm after administration of cortisone, cAMP, hydrocortisone-acetate. Prolonged administration of ACTH maintains high level of enzyme in the mitochondria and microsomes. Hydrocortisone-acetate, insulin and cortisone decrease drastically enzyme in mitochondria."} {"id": "PMID:179845", "title": "Immunohistochemical study of the pars intermediate of the mouse pituitary in different experimental conditions.", "content": "Alpha-MSH, beta-MSH and ACTH have been localized in the cells of hypophyseal intermediate lobe by fluorescence histoimmunological technics. Elaboration and excretion of these polypeptides are enhanced after dehydration or adrenalectomy. The most evident variations are seen with alpha-MSH and ACTH after dehydration, with beta-MSH after adrenalectomy.", "contents": "Immunohistochemical study of the pars intermediate of the mouse pituitary in different experimental conditions. Alpha-MSH, beta-MSH and ACTH have been localized in the cells of hypophyseal intermediate lobe by fluorescence histoimmunological technics. Elaboration and excretion of these polypeptides are enhanced after dehydration or adrenalectomy. The most evident variations are seen with alpha-MSH and ACTH after dehydration, with beta-MSH after adrenalectomy."} {"id": "PMID:179849", "title": "[Effect of autonomotropic agents and their combinations with amidopyrine on aesptic inflammation and vascular permeability].", "content": "Experiments staged on rats demonstrated the display of antiexudative activity by phepracet, deseryl, chlorpromazine, phentolamine and sanotension in an inflammation produced through subplantar introduction of the Difco agar. Some of the above agents suppressed the reaction in response to dimethyl sulfoxide injection. The antiedematous and stabilizing the cellular membranes effects of amidopyrine were potentiated by using the latter in combination with sympatholytics and also with benactyzine. No synergism with respect to changes of the vascular permeability and kinnase activity of the blood was revealed.", "contents": "[Effect of autonomotropic agents and their combinations with amidopyrine on aesptic inflammation and vascular permeability]. Experiments staged on rats demonstrated the display of antiexudative activity by phepracet, deseryl, chlorpromazine, phentolamine and sanotension in an inflammation produced through subplantar introduction of the Difco agar. Some of the above agents suppressed the reaction in response to dimethyl sulfoxide injection. The antiedematous and stabilizing the cellular membranes effects of amidopyrine were potentiated by using the latter in combination with sympatholytics and also with benactyzine. No synergism with respect to changes of the vascular permeability and kinnase activity of the blood was revealed."} {"id": "PMID:179850", "title": "[Effect of catecholamines on the activity of rabbit kidney microsomal (na+--k+)-activated atpase].", "content": "The significance of alpha- and beta-adrenoreceptors and the role of cyclic 3', 5' -AMP in the mechanism of the activation by catecholamines of the microsoma (Na+ - K+)-activated ATP-ase of the rabbits kidneys were investigated. Phentolamine did not obstruct the activating effect of epinephrine in the cortical and medullar layer. Inderal inhibited the reaction of the enzyme in response to epinephrine in the renal cortex and fully prevented any rise of the enzymatic activity in the medullar substances. Isopropylnorpinephrine and cyclic 3',5' -AMP stimulated the (Na+ - K+)-activated ATP-ase in the cortical and medullar layer. An inference is drawn to the effect that the activation of the enzyme occurring under the effect of catecholamines comes as a consequence of a beta-adrenoreceptors stimulation. It is suggested that the cyclic 3',5'-AMP may be directly involved in the mechanism accounting for stimulation by catecholamines of the activity displayed by the microsomal (Na+ - K+)-activated ATP-ase of the rabbits kidneys.", "contents": "[Effect of catecholamines on the activity of rabbit kidney microsomal (na+--k+)-activated atpase]. The significance of alpha- and beta-adrenoreceptors and the role of cyclic 3', 5' -AMP in the mechanism of the activation by catecholamines of the microsoma (Na+ - K+)-activated ATP-ase of the rabbits kidneys were investigated. Phentolamine did not obstruct the activating effect of epinephrine in the cortical and medullar layer. Inderal inhibited the reaction of the enzyme in response to epinephrine in the renal cortex and fully prevented any rise of the enzymatic activity in the medullar substances. Isopropylnorpinephrine and cyclic 3',5' -AMP stimulated the (Na+ - K+)-activated ATP-ase in the cortical and medullar layer. An inference is drawn to the effect that the activation of the enzyme occurring under the effect of catecholamines comes as a consequence of a beta-adrenoreceptors stimulation. It is suggested that the cyclic 3',5'-AMP may be directly involved in the mechanism accounting for stimulation by catecholamines of the activity displayed by the microsomal (Na+ - K+)-activated ATP-ase of the rabbits kidneys."} {"id": "PMID:179851", "title": "[Effect of polyvinylpyridine N-oxide on lipid metabolism indices in healthy and silicotic rats].", "content": "In the early period of investigations (in 1 month) polyvinylpyridine-N-oxide (PNO) causes a fall in the content of lipid compounds (total lipids, phospholipids, choesterol) in the liver and an inhibition of the lipolytic activity in the tissue of intratracheally quartzdust laden rats. Introduction of PNO into the lungs of dust-laden rats over a period of 4 months produces an appreciable diminution in the quantity of all the lipid components against the background of an increased lipolytic activity, recuced under the effect of quartz dust. In healthy rats PNO depresses the lipolytic activity of the pulmonary tissue and intermittently brings down the lipid compounds therein and in the spleen. In the blood of healthy and silicotic rats receiging PNO the level of the total and free cholesterol goes up. Early after administration of PNO the content of total lipids and beta-lipoproteids in the blood serum of dust-laden rats augments, while later on the concentration of total lipids goes down, while the level of summary ketone bodies rises.", "contents": "[Effect of polyvinylpyridine N-oxide on lipid metabolism indices in healthy and silicotic rats]. In the early period of investigations (in 1 month) polyvinylpyridine-N-oxide (PNO) causes a fall in the content of lipid compounds (total lipids, phospholipids, choesterol) in the liver and an inhibition of the lipolytic activity in the tissue of intratracheally quartzdust laden rats. Introduction of PNO into the lungs of dust-laden rats over a period of 4 months produces an appreciable diminution in the quantity of all the lipid components against the background of an increased lipolytic activity, recuced under the effect of quartz dust. In healthy rats PNO depresses the lipolytic activity of the pulmonary tissue and intermittently brings down the lipid compounds therein and in the spleen. In the blood of healthy and silicotic rats receiging PNO the level of the total and free cholesterol goes up. Early after administration of PNO the content of total lipids and beta-lipoproteids in the blood serum of dust-laden rats augments, while later on the concentration of total lipids goes down, while the level of summary ketone bodies rises."} {"id": "PMID:179852", "title": "[Changes in the functional state and structure of the adrenals in CC14 poisoning].", "content": "Introduction of CCI4 in doses of 0.1 and 0.2 ml/100 g to albino rats reduced the steroid production generated by adrenal sections. In 24 and 48 hours after poisoning with a small dose of CCI4 (0.1 ml/100 g) there could be seen an increased concentration of 11-oxycorticosteroids in the plasma. Morphological signs of a damage suffered by the gland were observed only in poisoning with a large dose of CCI4 (0.2 ml/100 g).", "contents": "[Changes in the functional state and structure of the adrenals in CC14 poisoning]. Introduction of CCI4 in doses of 0.1 and 0.2 ml/100 g to albino rats reduced the steroid production generated by adrenal sections. In 24 and 48 hours after poisoning with a small dose of CCI4 (0.1 ml/100 g) there could be seen an increased concentration of 11-oxycorticosteroids in the plasma. Morphological signs of a damage suffered by the gland were observed only in poisoning with a large dose of CCI4 (0.2 ml/100 g)."} {"id": "PMID:179853", "title": "[Effect of psychotropic and anticonvulsant preparations on the conformational transitions in transport ATPase].", "content": "The effect of neuroleptics, antidepressants, somnifacients and antiepileptic drugs on Na+- and K+-dependent transitions in the preparation of the transport ATP-ase from renal tubules of the guinea pig were looked into by using the spinal probes procedures. Neuroleptics inhibit most strongly (by 100--67 per cent) the conformant transition in the Na+- K+-dependent ATP-ase, their action manifesting itself to a greater extent with respect to the K+-dependent conformant transitions. The influence of antidepressants is close to that of the neuroleptics, although it is noticeably less intensive (78--46 per cent). The action of hypnotics (barbituric acid derivatives) and of antiepileptic drugs of a different chemical structure closely approaches, but is different from the effect of neuroleptics and antidepressants, both as concerns its intensity and the lack of any essential differences in the action upon the Na+- and K+-dependant conformant transitions.", "contents": "[Effect of psychotropic and anticonvulsant preparations on the conformational transitions in transport ATPase]. The effect of neuroleptics, antidepressants, somnifacients and antiepileptic drugs on Na+- and K+-dependent transitions in the preparation of the transport ATP-ase from renal tubules of the guinea pig were looked into by using the spinal probes procedures. Neuroleptics inhibit most strongly (by 100--67 per cent) the conformant transition in the Na+- K+-dependent ATP-ase, their action manifesting itself to a greater extent with respect to the K+-dependent conformant transitions. The influence of antidepressants is close to that of the neuroleptics, although it is noticeably less intensive (78--46 per cent). The action of hypnotics (barbituric acid derivatives) and of antiepileptic drugs of a different chemical structure closely approaches, but is different from the effect of neuroleptics and antidepressants, both as concerns its intensity and the lack of any essential differences in the action upon the Na+- and K+-dependant conformant transitions."} {"id": "PMID:179855", "title": "[Effect of aminazine and haloperidol on caudate inhibition of the conditioned reflex reaction of avoidance in cats].", "content": "The effect of neuroleptics on the avoidance behaviour under electric low-frequency stimulation of the caudate neucleus was studied in experiments with cats. Chlorpromazine (1 and 3 mg/kg) and haloperidol (0.5 mg/kg) were found to bring disorder in the behaviour of the animals and to intensify the inhibitory function of the caudate nucleus. Chlorpromazine proved in all respects to be a more active substance. The results obtained may be attributed to disruption of the central dopamine- and noradrenergic transmission.", "contents": "[Effect of aminazine and haloperidol on caudate inhibition of the conditioned reflex reaction of avoidance in cats]. The effect of neuroleptics on the avoidance behaviour under electric low-frequency stimulation of the caudate neucleus was studied in experiments with cats. Chlorpromazine (1 and 3 mg/kg) and haloperidol (0.5 mg/kg) were found to bring disorder in the behaviour of the animals and to intensify the inhibitory function of the caudate nucleus. Chlorpromazine proved in all respects to be a more active substance. The results obtained may be attributed to disruption of the central dopamine- and noradrenergic transmission."} {"id": "PMID:179854", "title": "[Excitability of the hypothalamus and limbic structures of the rabbit brain under the influence of glucocorticoids and ACTH].", "content": "The influence of glucocorticoids and ACTH on the excitability of the hypothalamus and limbic structures of the brain in rabbits was studied in chronic tests with electrochemotrodes preliminarily implanted into the brain. Results bearing proof to a dissimilar effect produced by ACTH and glucocorticoids on the excitability of the anterior and posterior hypothalamus, hippocampus and amygdala are presented. It is suggested that the mechanism of the retroinhibitory action of corticosteroids and ACTH provides for the participation of hypothalamic and limbic structures of the brain.", "contents": "[Excitability of the hypothalamus and limbic structures of the rabbit brain under the influence of glucocorticoids and ACTH]. The influence of glucocorticoids and ACTH on the excitability of the hypothalamus and limbic structures of the brain in rabbits was studied in chronic tests with electrochemotrodes preliminarily implanted into the brain. Results bearing proof to a dissimilar effect produced by ACTH and glucocorticoids on the excitability of the anterior and posterior hypothalamus, hippocampus and amygdala are presented. It is suggested that the mechanism of the retroinhibitory action of corticosteroids and ACTH provides for the participation of hypothalamic and limbic structures of the brain."} {"id": "PMID:179860", "title": "Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas.", "content": "Xanthine oxidase was decreased 2- to 10-fold in all examined rat hepatomas irrespective of the malignancy; growth rate and degrees of histological differentiation of the neoplasms. The affinity to substrate (KM=6-8 muM) and the pH optimum (8.0) of the liver and hepatoma enzymes were the same. The reprogramming of gene expression, as manifested in the decreased activity of this key purine metabolizing enzyme, appears to be specific to neoplastic transformation. Since glutamine PRPP amidotransferase activity was increased but the opposing enzyme, xanthine oxidase, was decreased in all the hepatomas, the reprogramming of gene expression results in an imbalance that favors synthesis against catabolism. This enzymatic imbalance should confer selective advantages to the cancer cells.", "contents": "Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. Xanthine oxidase was decreased 2- to 10-fold in all examined rat hepatomas irrespective of the malignancy; growth rate and degrees of histological differentiation of the neoplasms. The affinity to substrate (KM=6-8 muM) and the pH optimum (8.0) of the liver and hepatoma enzymes were the same. The reprogramming of gene expression, as manifested in the decreased activity of this key purine metabolizing enzyme, appears to be specific to neoplastic transformation. Since glutamine PRPP amidotransferase activity was increased but the opposing enzyme, xanthine oxidase, was decreased in all the hepatomas, the reprogramming of gene expression results in an imbalance that favors synthesis against catabolism. This enzymatic imbalance should confer selective advantages to the cancer cells."} {"id": "PMID:179856", "title": "[Study of the process of ACTH and insulin interaction with the plasmatic membranes of rat liver cells in vitro using luminescence methods].", "content": "The process of interaction of ACTH and insulin with plasmatic cellular membranes of the rat's liver and artificial lipid membranes (liposomes) was studied by the method of proper proteinic fluorescence and by using hydrophobic fluorescent probes. This process is shown to be attended by conformative readjustments of the membranous proteins and also by definite structural changes in the lipid phase of the membranes. In its action ACTH involves the hydrophobic layer of the lipid phase to a greater extent than does insulin. A comparison of the data on the effect produced by ACTH and insulin on the plasmatic membranes as against the results obtained with liposomes suggests that for the hormones to display their activity these have first to combine with the specific membranous protein, while a change in the lipid phase comes only as a consequence of such an interaction.", "contents": "[Study of the process of ACTH and insulin interaction with the plasmatic membranes of rat liver cells in vitro using luminescence methods]. The process of interaction of ACTH and insulin with plasmatic cellular membranes of the rat's liver and artificial lipid membranes (liposomes) was studied by the method of proper proteinic fluorescence and by using hydrophobic fluorescent probes. This process is shown to be attended by conformative readjustments of the membranous proteins and also by definite structural changes in the lipid phase of the membranes. In its action ACTH involves the hydrophobic layer of the lipid phase to a greater extent than does insulin. A comparison of the data on the effect produced by ACTH and insulin on the plasmatic membranes as against the results obtained with liposomes suggests that for the hormones to display their activity these have first to combine with the specific membranous protein, while a change in the lipid phase comes only as a consequence of such an interaction."} {"id": "PMID:179897", "title": "Tubal plastic surgery at the Tel Hashomer Hospital: a critical study.", "content": "The study presents 93 patients in whom tubal surgery was carried out for primary or secondary mechanical infertility. A classification of these patients into five groups is suggested. Twenty-four uterine pregnancies were recorded, eighteen of which reached term. A plea for enlarging the scope and number of interventions in more patients of the older group and of the more complex pathologic group is presented and discussed. This approach may lower the the over-all success rate but may benefit some of this group of patients. Last but not least, the follow-up of these patients, who constantly move from one physician to another, seeking more treatment, is difficult. Liaison with referring gynecologists and standardization of methods would be of great help in the follow-up.", "contents": "Tubal plastic surgery at the Tel Hashomer Hospital: a critical study. The study presents 93 patients in whom tubal surgery was carried out for primary or secondary mechanical infertility. A classification of these patients into five groups is suggested. Twenty-four uterine pregnancies were recorded, eighteen of which reached term. A plea for enlarging the scope and number of interventions in more patients of the older group and of the more complex pathologic group is presented and discussed. This approach may lower the the over-all success rate but may benefit some of this group of patients. Last but not least, the follow-up of these patients, who constantly move from one physician to another, seeking more treatment, is difficult. Liaison with referring gynecologists and standardization of methods would be of great help in the follow-up."} {"id": "PMID:179900", "title": "[Active transport of fluorescein in the choroid plexus of the brain and regulation of its rate by cyclic 3',5'-AMP].", "content": "With the aid of luminescent microscopy and microfluorimetry in vitro, the transport of labelled fluorescine into the structures of the brain lateral ventricles' chorioid plexus was studied in rabbits. An against-gradient pumping of fluorescine into the cytoplasm of the neuroepithelium cells and into the lumen of adjucent capillaries was shown to occur in the chorioid plexus. Such accumulation of fluorescine proceeds in the active transport way with participation of a carrier. The active transport system is congenial to fluorescine - Km = 4-10(-5) M, which renders even small amounts of this substance to be quickly removed from the milieu. The fluorescine-transporting system fulfills transition of other organic acids as well. The system of organic acids active transport is, apparently, localized in the apical and basal membranes of the neuroepithelial cells surrounding the plexus' filia which makes the concentration of transported acid in the neuroepithelial cells higher than in milieu, and in the capillaries' lumen higher than in the cytoplasm. An enzyme system adenylcyclasa-phosphodiesterase was found in the chorioid plexus' neuroepithelium. The system participates in regulation of velocity of the organic acids transport by means of changing the intracellular concentration 3',5'-AMP.", "contents": "[Active transport of fluorescein in the choroid plexus of the brain and regulation of its rate by cyclic 3',5'-AMP]. With the aid of luminescent microscopy and microfluorimetry in vitro, the transport of labelled fluorescine into the structures of the brain lateral ventricles' chorioid plexus was studied in rabbits. An against-gradient pumping of fluorescine into the cytoplasm of the neuroepithelium cells and into the lumen of adjucent capillaries was shown to occur in the chorioid plexus. Such accumulation of fluorescine proceeds in the active transport way with participation of a carrier. The active transport system is congenial to fluorescine - Km = 4-10(-5) M, which renders even small amounts of this substance to be quickly removed from the milieu. The fluorescine-transporting system fulfills transition of other organic acids as well. The system of organic acids active transport is, apparently, localized in the apical and basal membranes of the neuroepithelial cells surrounding the plexus' filia which makes the concentration of transported acid in the neuroepithelial cells higher than in milieu, and in the capillaries' lumen higher than in the cytoplasm. An enzyme system adenylcyclasa-phosphodiesterase was found in the chorioid plexus' neuroepithelium. The system participates in regulation of velocity of the organic acids transport by means of changing the intracellular concentration 3',5'-AMP."} {"id": "PMID:179901", "title": "[Analysis of an increase in the body's sensitivity to insulin].", "content": "In adult albino rats, increased sentivity of the organism to insulin action caused by systematic muscular exercises preserved in conditions of adrenergic blockade but was reduced by theophylline administration (inhibition of 3'-5'-AMP-phosphodiesterase activity). The sensitivity to insulin action 3'-5'-phosphodiesterase (in muscles, liver, and adipose tissue) increased during adaptation to muscular activity. Simultaneously the insulin inactivation in muscle and liver tissues also increased.", "contents": "[Analysis of an increase in the body's sensitivity to insulin]. In adult albino rats, increased sentivity of the organism to insulin action caused by systematic muscular exercises preserved in conditions of adrenergic blockade but was reduced by theophylline administration (inhibition of 3'-5'-AMP-phosphodiesterase activity). The sensitivity to insulin action 3'-5'-phosphodiesterase (in muscles, liver, and adipose tissue) increased during adaptation to muscular activity. Simultaneously the insulin inactivation in muscle and liver tissues also increased."} {"id": "PMID:179902", "title": "[The activity of 3',5'-AMP phosphodiesterase and inactivation of insulin during muscular activity].", "content": "In trained adult albino rats, more rapid mobilization of carbohydrates and FFA, more economical carbohydrates expenditure during muscular exercise, and more rapid resynthesis of glycogen during recovery period, were observed. This depends on both the changes of 3',5'-AMP-phosphodiesterase activity of muscles, liver, and adipose tissue, and the degree of insulin inactivation by muscle and liver tissues. Both these processes considerably differ in untrained and trained animals.", "contents": "[The activity of 3',5'-AMP phosphodiesterase and inactivation of insulin during muscular activity]. In trained adult albino rats, more rapid mobilization of carbohydrates and FFA, more economical carbohydrates expenditure during muscular exercise, and more rapid resynthesis of glycogen during recovery period, were observed. This depends on both the changes of 3',5'-AMP-phosphodiesterase activity of muscles, liver, and adipose tissue, and the degree of insulin inactivation by muscle and liver tissues. Both these processes considerably differ in untrained and trained animals."} {"id": "PMID:179903", "title": "Detection of RNA-instructed DNA polymerase in the mitochondria of Rous sarcoma cells using sephadex G-150 thin-layer gel filtration.", "content": "Analyses of the DNA polymerase present in the inner mitochondrial membrane and matrix fraction of the mitochondria isolated from Rous sarcoma cells and chick embryo cells, and in the lysate of Rous sarcoma virus were performed, using a modification of the thin-layer gel filtration on Sephadex G-150 superfine. The method allowed the simultaneous determination of the molecular weight of the isolated enzymes. In the mitochondria or Rous sarcoma cells an RNA-directed DNA polymerase, activated by poly(rA): oligo (dT) synthetic duplex, was detected, with the same molecular weight as the reverse transcriptase isolated from Rous sarcoma virus. Such enzyme was not found in the mitochondria of chick embryo cells.", "contents": "Detection of RNA-instructed DNA polymerase in the mitochondria of Rous sarcoma cells using sephadex G-150 thin-layer gel filtration. Analyses of the DNA polymerase present in the inner mitochondrial membrane and matrix fraction of the mitochondria isolated from Rous sarcoma cells and chick embryo cells, and in the lysate of Rous sarcoma virus were performed, using a modification of the thin-layer gel filtration on Sephadex G-150 superfine. The method allowed the simultaneous determination of the molecular weight of the isolated enzymes. In the mitochondria or Rous sarcoma cells an RNA-directed DNA polymerase, activated by poly(rA): oligo (dT) synthetic duplex, was detected, with the same molecular weight as the reverse transcriptase isolated from Rous sarcoma virus. Such enzyme was not found in the mitochondria of chick embryo cells."} {"id": "PMID:179904", "title": "Separation of time-defined avian myeloblastosis virus (AMV) using column cultivation of leukaemic myeblasts.", "content": "A new technique is described of column cultivation of cells immobilized on Sial glass cullet. The technique ensures a controlled and continuous production of time-defined young virus. During the column cultivation the morphological characteristics of tho immobilized cells remain essentially unchanged.", "contents": "Separation of time-defined avian myeloblastosis virus (AMV) using column cultivation of leukaemic myeblasts. A new technique is described of column cultivation of cells immobilized on Sial glass cullet. The technique ensures a controlled and continuous production of time-defined young virus. During the column cultivation the morphological characteristics of tho immobilized cells remain essentially unchanged."} {"id": "PMID:179906", "title": "Inhibition of lymphocyte blastogenesis by factor(s) in alloxan-diabetic rat plasma.", "content": "Supplementation of rat lymphocyte cultures with plasma from alloxan-diabetic rats produced a dose-dependent suppression of mitogen-induced blastogenic responses. Viability measurements indicated that this inhibition was not due to a direct cytotoxic effect of alloxan-diabetic plasma on rat mononuclear leukocytes in vitro. This inhibition was not explained by hyperglycemia alone and was observed when blastogenesis was induced in vitro by phytohemagglutinin (PHA), concanavalin A (con A), or allogeneic cells. Peripheral blood lymphocytes from alloxan-diabetic rats appeared to be more sensitive than normal cells to the inhibitory effect of diabetic plasma. Heating at 56 degrees for 60 minutes produced only a partial loss of the inhibition by diabetic plasma. Alloxan-diabetic rat plasma promoted an increased accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in mononuclear leukocytes. Insulin (1 and 100 muU./ml.) in vitro enhanced PHA-induced blastogenesis but failed to reverse the inhibition caused by diabetic plasma. Ultrafiltration through a cellulose dialysis membrane with an exclusion size of 12,000 molecular weight did not remove the inhibitory factor(s). These results indicate that a depressed cellular immune response is produced during an insulin-deficient diabetic state. The suppressed in-vitro blastogenic response of lymphocytes from alloxan-diabetic rats appears to involve some circulating inhibitory factor(s) in diabetic plasma. This inhibition may be explained, in part, by the ability of diabetic plasma to elevate cyclic AMP in mononuclear leukocytes.", "contents": "Inhibition of lymphocyte blastogenesis by factor(s) in alloxan-diabetic rat plasma. Supplementation of rat lymphocyte cultures with plasma from alloxan-diabetic rats produced a dose-dependent suppression of mitogen-induced blastogenic responses. Viability measurements indicated that this inhibition was not due to a direct cytotoxic effect of alloxan-diabetic plasma on rat mononuclear leukocytes in vitro. This inhibition was not explained by hyperglycemia alone and was observed when blastogenesis was induced in vitro by phytohemagglutinin (PHA), concanavalin A (con A), or allogeneic cells. Peripheral blood lymphocytes from alloxan-diabetic rats appeared to be more sensitive than normal cells to the inhibitory effect of diabetic plasma. Heating at 56 degrees for 60 minutes produced only a partial loss of the inhibition by diabetic plasma. Alloxan-diabetic rat plasma promoted an increased accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in mononuclear leukocytes. Insulin (1 and 100 muU./ml.) in vitro enhanced PHA-induced blastogenesis but failed to reverse the inhibition caused by diabetic plasma. Ultrafiltration through a cellulose dialysis membrane with an exclusion size of 12,000 molecular weight did not remove the inhibitory factor(s). These results indicate that a depressed cellular immune response is produced during an insulin-deficient diabetic state. The suppressed in-vitro blastogenic response of lymphocytes from alloxan-diabetic rats appears to involve some circulating inhibitory factor(s) in diabetic plasma. This inhibition may be explained, in part, by the ability of diabetic plasma to elevate cyclic AMP in mononuclear leukocytes."} {"id": "PMID:179907", "title": "Individual differences in infants' sleep.", "content": "Individual differences in sleep patterns were repeatedly studied in 22 infants in a residential unit for mothers and babies at two, six, 12 and 20 weeks of age. Electroencephalogram, horizontal and vertical electro-oculogram, electromyogram of chin muscle, and respiration and body movements were recorded during the first two sleep cycles. The age factor was significant in all variables studied. The infants' individuality was significant in (1) the frequency of respiration during quiet sleep, (2) the frequency of rapid eye movement during paradoxical sleep, (3) the occurrence of regular EEG activity during paradoxical sleep, and (4) body movements during paradoxical sleep. Individual differences in these sleep variables persisted with considerable stability during the first five months of life.", "contents": "Individual differences in infants' sleep. Individual differences in sleep patterns were repeatedly studied in 22 infants in a residential unit for mothers and babies at two, six, 12 and 20 weeks of age. Electroencephalogram, horizontal and vertical electro-oculogram, electromyogram of chin muscle, and respiration and body movements were recorded during the first two sleep cycles. The age factor was significant in all variables studied. The infants' individuality was significant in (1) the frequency of respiration during quiet sleep, (2) the frequency of rapid eye movement during paradoxical sleep, (3) the occurrence of regular EEG activity during paradoxical sleep, and (4) body movements during paradoxical sleep. Individual differences in these sleep variables persisted with considerable stability during the first five months of life."} {"id": "PMID:179908", "title": "Hepatoma occurring two decades after hepatic irradiation.", "content": "Hepatoma has been related to chemical, dietary, metabolic, infectious, and genetic factors. therapeutic hepatic irradiation has never been associated with hepatoma. A case of hepatocellular carcinoma is presented that occurred two decades after radiotherapy for presumed hepatic hemangioma. Radiation-related liver disease is discussed in general, with emphasis placed on radiation hepatocarcinogenesis.", "contents": "Hepatoma occurring two decades after hepatic irradiation. Hepatoma has been related to chemical, dietary, metabolic, infectious, and genetic factors. therapeutic hepatic irradiation has never been associated with hepatoma. A case of hepatocellular carcinoma is presented that occurred two decades after radiotherapy for presumed hepatic hemangioma. Radiation-related liver disease is discussed in general, with emphasis placed on radiation hepatocarcinogenesis."} {"id": "PMID:179909", "title": "Inhibition by propranolol of bile acid stimulation of rabbit colonic adenylate cyclase in vitro.", "content": "Bile acids, especially unconjugated deoxycholic acid, cause diarrhea by inducing colonic mucosal secretion of water and electrolytes. This effect has been shown to be mediated by adenylate cyclase (AC). Propranolol, a beta-adrenergic blocking agent which inhibits AC, may then prevent this action of bile acids on colonic mucosa. The aim of this study was to determine the effect of bile acids, catecholamines, and propranolol on AC activity in colonic mucosa. The in vitro effects of deoxycholic acid, taurocholic acid, NaF, epinephrine, norepinephrine, and propranolol on AC in rabbit colonic mucosa were determined. NaF, 10(-4) M, increased AC activity to 220% of control (P less than 0.01). Deoxycholic acid, 10(-4) M, increased AC activity to 178% of control (P less than 0.01). Lesser but significant (P less than 0.01) stimulation of AC occurred at both higher and lower concentrations of deoxycholic acid, with no effect at 10(-10) M. Taurocholic acid, 10(-4) M, and epinephrine and norepinephrine, 10(-2) M, 10(-4) M, 10(-6) M, and 10(-8) M, had no effect on AC. Propranolol, 10(-6) M, caused a 60% decrease (P less than 0.01) in the stimulated AC activity induced by 10(-4) M deoxycholic acid. Propranolol, 10(-4) M, decreased basal AC by 30% (P less than 0.01). (1) Deoxycholic acid, but not taurocholic acid, epinephrine, or norepinephrine, stimulates colonic AC activity. (2) Propranolol inhibited this deoxycholic acid stimulation of AC. (3) Catecholamines are not intermediaries in this action of propranolol on colonic mucosal AC activity.", "contents": "Inhibition by propranolol of bile acid stimulation of rabbit colonic adenylate cyclase in vitro. Bile acids, especially unconjugated deoxycholic acid, cause diarrhea by inducing colonic mucosal secretion of water and electrolytes. This effect has been shown to be mediated by adenylate cyclase (AC). Propranolol, a beta-adrenergic blocking agent which inhibits AC, may then prevent this action of bile acids on colonic mucosa. The aim of this study was to determine the effect of bile acids, catecholamines, and propranolol on AC activity in colonic mucosa. The in vitro effects of deoxycholic acid, taurocholic acid, NaF, epinephrine, norepinephrine, and propranolol on AC in rabbit colonic mucosa were determined. NaF, 10(-4) M, increased AC activity to 220% of control (P less than 0.01). Deoxycholic acid, 10(-4) M, increased AC activity to 178% of control (P less than 0.01). Lesser but significant (P less than 0.01) stimulation of AC occurred at both higher and lower concentrations of deoxycholic acid, with no effect at 10(-10) M. Taurocholic acid, 10(-4) M, and epinephrine and norepinephrine, 10(-2) M, 10(-4) M, 10(-6) M, and 10(-8) M, had no effect on AC. Propranolol, 10(-6) M, caused a 60% decrease (P less than 0.01) in the stimulated AC activity induced by 10(-4) M deoxycholic acid. Propranolol, 10(-4) M, decreased basal AC by 30% (P less than 0.01). (1) Deoxycholic acid, but not taurocholic acid, epinephrine, or norepinephrine, stimulates colonic AC activity. (2) Propranolol inhibited this deoxycholic acid stimulation of AC. (3) Catecholamines are not intermediaries in this action of propranolol on colonic mucosal AC activity."} {"id": "PMID:179910", "title": "Propranolol inhibits adenylate cyclase and secretion stimulated by deoxycholic acid in the rabbit colon.", "content": "Bile acids cause diarrhea by inducing colonic secretion, probably mediated through the cyclic AMP system. The aim was to determine the effects of an adenylate cyclase inhibitor, propranolol, on deoxycholic acid (DCA) stimulation of net secretion and the cyclic AMP system in the colon. In each of 30 New Zealand white rabbits, 0.9% NaC1 as control and 6 mM and 8 mM DCA were injected in random sequence into three colonic loops in situ. Propranolol, 4 mg per kg was administered intravenously to 12 of the 30 rabbits 1/2 hr before preparation of the loops, i.e., 5 1/2 hr before the rabbits were killed. In the 18 untreated animals, 6 and 8 mM DCA significantly stimulated colonic net secretion and mucosal adenylate cyclase activity; 6 mM DCA caused no change in mucosal phosphodiesterase activity, whereas 8 mM DCA caused a 25% decrease (P less than 0.01). In propranolol-treated animals compared to untreated animals, the volume of luminal fluid in controls was not different, with 6 mM DCA it was 88% less (P less than 0.01), and with 8 mM DCA it was 45% less (P less than 0.01); adenylate cyclase activity in controls was 43% less (P less than 0.01), with 6 mM DCA it was 67% less (P less than 0.01), and with 8 mM DCA it was 65% less (P less than 0.01); phosphodiesterase activity in controls and with 6 mM DCA was not different and with 8 mM DCA it was 38% greater (P less than 0.02). In conclusion, propranolol prevented DCA stimulation of colonic net secretion and inhibited the cyclic AMP system. Propranolol, therefore, warrants investigation as therapy for diarrhea caused by bile acids in the colon.", "contents": "Propranolol inhibits adenylate cyclase and secretion stimulated by deoxycholic acid in the rabbit colon. Bile acids cause diarrhea by inducing colonic secretion, probably mediated through the cyclic AMP system. The aim was to determine the effects of an adenylate cyclase inhibitor, propranolol, on deoxycholic acid (DCA) stimulation of net secretion and the cyclic AMP system in the colon. In each of 30 New Zealand white rabbits, 0.9% NaC1 as control and 6 mM and 8 mM DCA were injected in random sequence into three colonic loops in situ. Propranolol, 4 mg per kg was administered intravenously to 12 of the 30 rabbits 1/2 hr before preparation of the loops, i.e., 5 1/2 hr before the rabbits were killed. In the 18 untreated animals, 6 and 8 mM DCA significantly stimulated colonic net secretion and mucosal adenylate cyclase activity; 6 mM DCA caused no change in mucosal phosphodiesterase activity, whereas 8 mM DCA caused a 25% decrease (P less than 0.01). In propranolol-treated animals compared to untreated animals, the volume of luminal fluid in controls was not different, with 6 mM DCA it was 88% less (P less than 0.01), and with 8 mM DCA it was 45% less (P less than 0.01); adenylate cyclase activity in controls was 43% less (P less than 0.01), with 6 mM DCA it was 67% less (P less than 0.01), and with 8 mM DCA it was 65% less (P less than 0.01); phosphodiesterase activity in controls and with 6 mM DCA was not different and with 8 mM DCA it was 38% greater (P less than 0.02). In conclusion, propranolol prevented DCA stimulation of colonic net secretion and inhibited the cyclic AMP system. Propranolol, therefore, warrants investigation as therapy for diarrhea caused by bile acids in the colon."} {"id": "PMID:179911", "title": "Utilization of the quantitative assay of lipoprotein X in the differential diagnosis of extraphepatic obstructive jaundice and intrahepatic diseases.", "content": "Quantitative determination of LP-X, abnormal serum low density lipoprotein, was performed on the sera of 620 patients with jaundice in two medical centers, one in Oklahoma City, Oklahoma, and the other in Birmingham, England. The results of serial assays over a period of 5 to 8 days after patient admission to hospital or after onset of jaundice, if this occurred in hospital, correlated best with the type and management of jaundice. In some cases of early cholestatic disease of extrahepatic origin LP-X may be absent, but after the observation period it was found that only 1 of 81 (98%) patients with obstruction of the extrahepatic bile duct system remained negative. Of the remainder, 74 (91%) had or developed levels of LP-X exceeding 300 mg per 100 ml. In addition, 43 (88%) of 49 subjects followed serially showed increases in LP-X concentration, with no change in 3 patients. Of 539 subjects with intrahepatic disease, 14 (26.5%) were LP-X positive and 27 (19.4%) of these had initial LP-X levels higher than 300 mg per 100 ml. During the follow-up period, 35 (74%) of 47 patients with intrahepatic disease showed a reduction of LP-X; of the remaining 12 patients 4 had mitochondrial antibody-positive primary biliary cirrhosis, and 6 had severe cholestasis associated with acute infectious hepatitis and high aspartate transaminase levels. Similar figures for alkaline phosphatase showed less consistent changes during the follow-up period. In this retrospective appraisal the trends and absolute levels of LP-X, in addition to the use of similarly followed levels of the routine liver function tests, allowed better differentiation of jaundice requiring surgical correction from that remediable by medical means exclusively than did the use of the routine liver function tests alone. In addition, LP-X is specific for liver dysfunction, whereas other routine liver function tests are not.", "contents": "Utilization of the quantitative assay of lipoprotein X in the differential diagnosis of extraphepatic obstructive jaundice and intrahepatic diseases. Quantitative determination of LP-X, abnormal serum low density lipoprotein, was performed on the sera of 620 patients with jaundice in two medical centers, one in Oklahoma City, Oklahoma, and the other in Birmingham, England. The results of serial assays over a period of 5 to 8 days after patient admission to hospital or after onset of jaundice, if this occurred in hospital, correlated best with the type and management of jaundice. In some cases of early cholestatic disease of extrahepatic origin LP-X may be absent, but after the observation period it was found that only 1 of 81 (98%) patients with obstruction of the extrahepatic bile duct system remained negative. Of the remainder, 74 (91%) had or developed levels of LP-X exceeding 300 mg per 100 ml. In addition, 43 (88%) of 49 subjects followed serially showed increases in LP-X concentration, with no change in 3 patients. Of 539 subjects with intrahepatic disease, 14 (26.5%) were LP-X positive and 27 (19.4%) of these had initial LP-X levels higher than 300 mg per 100 ml. During the follow-up period, 35 (74%) of 47 patients with intrahepatic disease showed a reduction of LP-X; of the remaining 12 patients 4 had mitochondrial antibody-positive primary biliary cirrhosis, and 6 had severe cholestasis associated with acute infectious hepatitis and high aspartate transaminase levels. Similar figures for alkaline phosphatase showed less consistent changes during the follow-up period. In this retrospective appraisal the trends and absolute levels of LP-X, in addition to the use of similarly followed levels of the routine liver function tests, allowed better differentiation of jaundice requiring surgical correction from that remediable by medical means exclusively than did the use of the routine liver function tests alone. In addition, LP-X is specific for liver dysfunction, whereas other routine liver function tests are not."} {"id": "PMID:179919", "title": "[Surgical treatment of ovarian tumors, especially ovarian carcinomas].", "content": "In every case of ovarian tumor or even if this possibility cannot be excluded by other means a diagnostic laparotomy is indicated. There are only a few exceptions to this rule. Before surgery every diagnostic step should be undertaken to determine the nature, extent and origin of the tumor. At laparotomy three situations may be found, 1. the tumor is obviously benign, 2. the nature of the tumor is doubtful and 3. the tumor is malignant. The diagnostic and therapeutic steps in all these situations and also in case of persistent or recurrent tumor are discussed. Treatment of ovarian cancer is radical surgery if possible and/or chemotherapy and radiation.", "contents": "[Surgical treatment of ovarian tumors, especially ovarian carcinomas]. In every case of ovarian tumor or even if this possibility cannot be excluded by other means a diagnostic laparotomy is indicated. There are only a few exceptions to this rule. Before surgery every diagnostic step should be undertaken to determine the nature, extent and origin of the tumor. At laparotomy three situations may be found, 1. the tumor is obviously benign, 2. the nature of the tumor is doubtful and 3. the tumor is malignant. The diagnostic and therapeutic steps in all these situations and also in case of persistent or recurrent tumor are discussed. Treatment of ovarian cancer is radical surgery if possible and/or chemotherapy and radiation."} {"id": "PMID:179923", "title": "[Experimental study on aldolase isozyme during the development of hepatoma in the rat (author's transl)].", "content": "Aldolase (ALD) consists of three different types of isozyme, i.e. muscle or A type, liver or B type and brain or C type, their relative proportions being fixed for each tissue. In this study, isozyme profiles in the serum and DAB induced hepatoma as it grows were examined in comparison with those in the fetal liver, in the hope to obtain information for early detection of the malady. In the very early phase of hepatoma growth with no elevated enzyme activity, ALD-A fraction after electrophoresis was found to increase. In the course of hepatoma growth, ALD-B decreased while ALD-A increased with appearance of hybrid of ALD-A and ALD-C. In the normal adult liver, no hybrid of ALD-A and ALD-C was encountered. Serum profile of the rat with DAB induced hepatoma was similar to that of the cancer tissue. On the other hand, the fetal liver shows a profile with high ALD-A fraction and even with hybrid of ALD-A and -C. These features disappeared gradually as maturation proceeded and became close to the adult pattern. Thus it is clear that DAB induced hepatoma exhibits retrogressive change in hepatic differentiation in its isozyme profile. The results also indicate usefulness of isozyme profile for early detection of the hepatoma.", "contents": "[Experimental study on aldolase isozyme during the development of hepatoma in the rat (author's transl)]. Aldolase (ALD) consists of three different types of isozyme, i.e. muscle or A type, liver or B type and brain or C type, their relative proportions being fixed for each tissue. In this study, isozyme profiles in the serum and DAB induced hepatoma as it grows were examined in comparison with those in the fetal liver, in the hope to obtain information for early detection of the malady. In the very early phase of hepatoma growth with no elevated enzyme activity, ALD-A fraction after electrophoresis was found to increase. In the course of hepatoma growth, ALD-B decreased while ALD-A increased with appearance of hybrid of ALD-A and ALD-C. In the normal adult liver, no hybrid of ALD-A and ALD-C was encountered. Serum profile of the rat with DAB induced hepatoma was similar to that of the cancer tissue. On the other hand, the fetal liver shows a profile with high ALD-A fraction and even with hybrid of ALD-A and -C. These features disappeared gradually as maturation proceeded and became close to the adult pattern. Thus it is clear that DAB induced hepatoma exhibits retrogressive change in hepatic differentiation in its isozyme profile. The results also indicate usefulness of isozyme profile for early detection of the hepatoma."} {"id": "PMID:179924", "title": "Hypoglycemia in diabetics.", "content": "Hypoglycemia in diabetes can be divided into 1) spontaneous hypoglycemic reactions due to absolute or relative overproduction of endogenous insulin or some other blood glucose-lowering substance, as in islet cell adenoma or carcinoma, latent or protodiabetic conditions, (extrapancreatic) tumors and pituitary and/or adrenal disorders; and 2) hypoglycemia caused by exogenous, i.e. therapeutic, measures. The problem of hypoglycemia in insulin-treated diabetics is far from being solved. As revealed by continuous blood glucose monitoring, nocturnal hypoglycemic attacks frequently escape attention especially in juvenile diabetics. Circadian variations in peripheral glucose utilization, rather than changes in plasma insulin activity, are likely to be involved in this mechanism. At least, this was the conclusion drawn from studies carried out by means of a glucose-controlled insulin and glucose infusion system (GCIGIS) -or artificial pancreas-which delivers short-acting insulin and glucose on demand intravenously. Hypoglycemic reactions in patients being treated with oral anti-diabetic agents, on the other hand, should be regarded primarily as one of the side reactions intrinsic to the mechanism of action of some of these drugs, e.g. sulfonylureas, which act mainly via stimulation of secretion of endogenous insulin reserves not responding properly to postprandial blood glucose increments. In the case of glibenclamide, at least partial resensitization of the defective glucose receptor of the beta-cell also becomes operative. A higher incidence of a characteristic type of hypoglycemic reaction was observed soon after glibenclamide therapy was introduced. Better understanding of the drug and dissemination of the information about it to doctors and patients has reduced the number of hypoglycemic reactions caused by glibenclamide to the same proportions as for other sulfonylureas. Hypoglyoemia following therapeutic hypophysectomy retains its position as one of the main hazards of this heroic therapy.", "contents": "Hypoglycemia in diabetics. Hypoglycemia in diabetes can be divided into 1) spontaneous hypoglycemic reactions due to absolute or relative overproduction of endogenous insulin or some other blood glucose-lowering substance, as in islet cell adenoma or carcinoma, latent or protodiabetic conditions, (extrapancreatic) tumors and pituitary and/or adrenal disorders; and 2) hypoglycemia caused by exogenous, i.e. therapeutic, measures. The problem of hypoglycemia in insulin-treated diabetics is far from being solved. As revealed by continuous blood glucose monitoring, nocturnal hypoglycemic attacks frequently escape attention especially in juvenile diabetics. Circadian variations in peripheral glucose utilization, rather than changes in plasma insulin activity, are likely to be involved in this mechanism. At least, this was the conclusion drawn from studies carried out by means of a glucose-controlled insulin and glucose infusion system (GCIGIS) -or artificial pancreas-which delivers short-acting insulin and glucose on demand intravenously. Hypoglycemic reactions in patients being treated with oral anti-diabetic agents, on the other hand, should be regarded primarily as one of the side reactions intrinsic to the mechanism of action of some of these drugs, e.g. sulfonylureas, which act mainly via stimulation of secretion of endogenous insulin reserves not responding properly to postprandial blood glucose increments. In the case of glibenclamide, at least partial resensitization of the defective glucose receptor of the beta-cell also becomes operative. A higher incidence of a characteristic type of hypoglycemic reaction was observed soon after glibenclamide therapy was introduced. Better understanding of the drug and dissemination of the information about it to doctors and patients has reduced the number of hypoglycemic reactions caused by glibenclamide to the same proportions as for other sulfonylureas. Hypoglyoemia following therapeutic hypophysectomy retains its position as one of the main hazards of this heroic therapy."} {"id": "PMID:179925", "title": "Human insulinoma tissue: in vitro studies of proinsulin/insulin biosynthesis and release.", "content": "The rate of proinsulin/insulin turnover has been studied in human insulinoma tissue from ten patients. During the incubation of tumor tissue the ratio of immunoreactive insulin (IRI) release to content was significantly higher than that from isolated human pancreatic islets. The tumor cell cytoplasm (100,000 g supernatant S-100) contained approximately 45% of the IRI. Endogenous proinsulin and insulin were released throughout the incubation. Newly synthesized proinsulin was detected in the 15 min pulse microsomal, secretory granule, S-100 and media samples. These results suggest that defective hormonal storage and release mechanisms are operative in human insulinoma cells resulting in a higher turnover of proinsulin and insulin compared with pancreatic islet tissue.", "contents": "Human insulinoma tissue: in vitro studies of proinsulin/insulin biosynthesis and release. The rate of proinsulin/insulin turnover has been studied in human insulinoma tissue from ten patients. During the incubation of tumor tissue the ratio of immunoreactive insulin (IRI) release to content was significantly higher than that from isolated human pancreatic islets. The tumor cell cytoplasm (100,000 g supernatant S-100) contained approximately 45% of the IRI. Endogenous proinsulin and insulin were released throughout the incubation. Newly synthesized proinsulin was detected in the 15 min pulse microsomal, secretory granule, S-100 and media samples. These results suggest that defective hormonal storage and release mechanisms are operative in human insulinoma cells resulting in a higher turnover of proinsulin and insulin compared with pancreatic islet tissue."} {"id": "PMID:179926", "title": "Glucagon secretion by the transplantable islet-cell tumor of the Syrian hamster.", "content": "The transplantable islet-cell tumor of the golden hamster has already been shown to produce hypoglycemia and hyperinsulinemia in the receptor animal. The present study demonstrates that the plasma pancreatic glucagon concentrations are significantly increased in the tumor-bearing animals but that this hyperglucagonemia is not abolished by administration of glucose or of diazoxide. It is also unresponsive to arginine administrations. In these animals, increased peripheral glucagon plasma concentrations are observed along with a reduced porto-aortic glucagon gradient. Moreover, plasma glucagon in the vena cava is usually higher than that in the aorta and a significant quantity of glucagon is found in the tumor. We conclude that glucagon release from the tumor is in fact responsible for the observed hyperglucagonemia.", "contents": "Glucagon secretion by the transplantable islet-cell tumor of the Syrian hamster. The transplantable islet-cell tumor of the golden hamster has already been shown to produce hypoglycemia and hyperinsulinemia in the receptor animal. The present study demonstrates that the plasma pancreatic glucagon concentrations are significantly increased in the tumor-bearing animals but that this hyperglucagonemia is not abolished by administration of glucose or of diazoxide. It is also unresponsive to arginine administrations. In these animals, increased peripheral glucagon plasma concentrations are observed along with a reduced porto-aortic glucagon gradient. Moreover, plasma glucagon in the vena cava is usually higher than that in the aorta and a significant quantity of glucagon is found in the tumor. We conclude that glucagon release from the tumor is in fact responsible for the observed hyperglucagonemia."} {"id": "PMID:179927", "title": "Response of islet cell tumors to enterohormones.", "content": "The insulin response to oral glucose, tolbutamide, arginine, pancreozymin and cerulein was studied in a group of subjects with insuloma and a group of normal control subjects. The same parameters were studied in a small number of cases after administration of secretin and gastrin. The glucagon response (IRG) to arginine, pancreozymin and cerulein was also studied. In subjects with insulomas plasma IRI values after oral glucose, tolbutamide and pancreozymin, starting from elevated basal levels, reached high absolute levels though the increase above basal levels did not differ significantly from normal. After cerulein plasma IRI values increased in some insuloma patients but not in normal subjects. After arginine the plasma IRI increase above basal levels was significantly lower than normal in patients with insulomas. The glucagon response to arginine was normal in the patients with insulomas; these patients showed a clearcut glucagon response to cerulein and a very irregular response after pancreozymin.", "contents": "Response of islet cell tumors to enterohormones. The insulin response to oral glucose, tolbutamide, arginine, pancreozymin and cerulein was studied in a group of subjects with insuloma and a group of normal control subjects. The same parameters were studied in a small number of cases after administration of secretin and gastrin. The glucagon response (IRG) to arginine, pancreozymin and cerulein was also studied. In subjects with insulomas plasma IRI values after oral glucose, tolbutamide and pancreozymin, starting from elevated basal levels, reached high absolute levels though the increase above basal levels did not differ significantly from normal. After cerulein plasma IRI values increased in some insuloma patients but not in normal subjects. After arginine the plasma IRI increase above basal levels was significantly lower than normal in patients with insulomas. The glucagon response to arginine was normal in the patients with insulomas; these patients showed a clearcut glucagon response to cerulein and a very irregular response after pancreozymin."} {"id": "PMID:179928", "title": "The diagnosis of insulinomas and other causes of fasting hypoglycemia.", "content": "The decrease in insulin secretion in normal subjects in response to hypoglycemia provides a basis for suppression tests for diagnosing insulinomas. The majority of patients with insulinomas have hypoglycemia after an overnight fast, and inordinatley raised plasma insulin levels are diagnostic. A prolonged fast is a means of enhancing hypoglycemia. Fish insulin can be used to induce hypoglycemia over a short period, and provides a simple, dynamic suppression test which appears to give good diagnostic discrimination. A normal endogenous insulin response to fish-insulin-induced hypoglycemia, together with clinical assessment and a few simple investigations, virtually excludes the diseases which cause fasting hypoglycemia in adults.", "contents": "The diagnosis of insulinomas and other causes of fasting hypoglycemia. The decrease in insulin secretion in normal subjects in response to hypoglycemia provides a basis for suppression tests for diagnosing insulinomas. The majority of patients with insulinomas have hypoglycemia after an overnight fast, and inordinatley raised plasma insulin levels are diagnostic. A prolonged fast is a means of enhancing hypoglycemia. Fish insulin can be used to induce hypoglycemia over a short period, and provides a simple, dynamic suppression test which appears to give good diagnostic discrimination. A normal endogenous insulin response to fish-insulin-induced hypoglycemia, together with clinical assessment and a few simple investigations, virtually excludes the diseases which cause fasting hypoglycemia in adults."} {"id": "PMID:179929", "title": "Medical treatment of endogenous organic hyperinsulinism.", "content": "There are several situations in which medical therapy of hyperinsulinism induced by islet cell tumors or hyperplasia is necessary and at present we have at our disposal several drugs which are capable of reducing endogenous hyperinsulinism. They are: -Streptozotocin, which represents today the most useful therapeutic agent for beta cell carcinoma therapy; -Diazoxide, which represents the drug of first choice for the treatment of most hypoglycemic syndromes caused by islet cell adenoma or hyperplasia; -Propranolol, Chlorpromazine, Diphenylhydantoin, which may be regarded as a useful alternative to diazoxide, although they are capable of giving rather inconstant results. These drugs may today effectively substitute for corticosteroids and glucagon in the medical treatment of almost every chronic hyperinsulinemic hypoglycemic syndrome, including malignant beta cell carcinoma.", "contents": "Medical treatment of endogenous organic hyperinsulinism. There are several situations in which medical therapy of hyperinsulinism induced by islet cell tumors or hyperplasia is necessary and at present we have at our disposal several drugs which are capable of reducing endogenous hyperinsulinism. They are: -Streptozotocin, which represents today the most useful therapeutic agent for beta cell carcinoma therapy; -Diazoxide, which represents the drug of first choice for the treatment of most hypoglycemic syndromes caused by islet cell adenoma or hyperplasia; -Propranolol, Chlorpromazine, Diphenylhydantoin, which may be regarded as a useful alternative to diazoxide, although they are capable of giving rather inconstant results. These drugs may today effectively substitute for corticosteroids and glucagon in the medical treatment of almost every chronic hyperinsulinemic hypoglycemic syndrome, including malignant beta cell carcinoma."} {"id": "PMID:179930", "title": "Onto- and phylogenetical aspects on insulin-producing islet-cell tumors.", "content": "When onto- and phylogenetical aspects are taken into account when studying insulin-producing islet-cell tumors, it becomes clear that the recently discovered \"type IV\" islet parenchymal cells (or \"delta 1\" -cells) may play an important role in various states of hypoglycemia, both of neoplastic and non-neoplastic origin. Moreover, it becomes obvious that increased attention to this kind of islet cell through intensified light-microscopical, histochemical, ultrastructural and experimental investigations covering a wide range of animals, may help to clarify several unsolved problems in the cytological composition of the islets of Langerhans. The occurrence of islet-cell tumors (or hamartomas) in the most primitive vertebrate islet parenchyma known, viz. that of the hagfish, Myxine glutinosa, is reported, as well as an additional case of mixed carcinoid-islet-cell tumor in a human pancreas.", "contents": "Onto- and phylogenetical aspects on insulin-producing islet-cell tumors. When onto- and phylogenetical aspects are taken into account when studying insulin-producing islet-cell tumors, it becomes clear that the recently discovered \"type IV\" islet parenchymal cells (or \"delta 1\" -cells) may play an important role in various states of hypoglycemia, both of neoplastic and non-neoplastic origin. Moreover, it becomes obvious that increased attention to this kind of islet cell through intensified light-microscopical, histochemical, ultrastructural and experimental investigations covering a wide range of animals, may help to clarify several unsolved problems in the cytological composition of the islets of Langerhans. The occurrence of islet-cell tumors (or hamartomas) in the most primitive vertebrate islet parenchyma known, viz. that of the hagfish, Myxine glutinosa, is reported, as well as an additional case of mixed carcinoid-islet-cell tumor in a human pancreas."} {"id": "PMID:179931", "title": "High-molecular IRI (big, big insulin) in islet cell adenoma.", "content": "In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue.", "contents": "High-molecular IRI (big, big insulin) in islet cell adenoma. In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue."} {"id": "PMID:179932", "title": "Oral glucose tolerance test (OGTT) during epinephrine infusion in three patients with insulomas.", "content": "An epinephrine infusion (6 mug/min) in three patients with insulomas inhibited insulin secretion induced by OGTT and increased glucagon secretion in two patients, with an exceptional rise in a case of poly-adenomatosis.", "contents": "Oral glucose tolerance test (OGTT) during epinephrine infusion in three patients with insulomas. An epinephrine infusion (6 mug/min) in three patients with insulomas inhibited insulin secretion induced by OGTT and increased glucagon secretion in two patients, with an exceptional rise in a case of poly-adenomatosis."} {"id": "PMID:179934", "title": "Histochemistry, ultrastructure and hormone content of human insulinomas.", "content": "Forty human insulin-producing tumors were investigated with histochemical, immunohistological and ultrastructural methods and extracted for insulin and proinsulin. These studies resulted in the following findings: 1) A variable number of tumor cells contained only a few or often no beta granules. 2) The insulin concentration was lower and the proinsulin percentage higher in insulinoma cells compared with normal beta-cells. 3) According to the ultrastructural appearance of the secretory granules four types of insulinoma were established. 4) Insulinomas frequently contained cells with atypical secretory granules which were Grimelius silver-positive. Their similarity to the Type IV islet cell and to cells regularly found in gastrinomas, Verner-Morrison tumors and glucagonomas suggests that all endocrine pancreatic tumors originate from a common precursor cell. 5) The morphological and biochemical findings support the theory that uncontrolled hormone release and/or decreased storage capacity are responsible for fasting hyperinsulinism in insulinoma patients. 6) The severity of hypoglycemia symptoms and the result of stimulatory tests were not related to the size, the insulin concentration and the total insulin content of the tumor.", "contents": "Histochemistry, ultrastructure and hormone content of human insulinomas. Forty human insulin-producing tumors were investigated with histochemical, immunohistological and ultrastructural methods and extracted for insulin and proinsulin. These studies resulted in the following findings: 1) A variable number of tumor cells contained only a few or often no beta granules. 2) The insulin concentration was lower and the proinsulin percentage higher in insulinoma cells compared with normal beta-cells. 3) According to the ultrastructural appearance of the secretory granules four types of insulinoma were established. 4) Insulinomas frequently contained cells with atypical secretory granules which were Grimelius silver-positive. Their similarity to the Type IV islet cell and to cells regularly found in gastrinomas, Verner-Morrison tumors and glucagonomas suggests that all endocrine pancreatic tumors originate from a common precursor cell. 5) The morphological and biochemical findings support the theory that uncontrolled hormone release and/or decreased storage capacity are responsible for fasting hyperinsulinism in insulinoma patients. 6) The severity of hypoglycemia symptoms and the result of stimulatory tests were not related to the size, the insulin concentration and the total insulin content of the tumor."} {"id": "PMID:179935", "title": "The federal mental health program: past, present, and future.", "content": "Dr. Brown traces the history of America's federal mental health program from its beginning in the early 1900s. NIMH, the institute he currently directs, was established in 1946 for the treatment and prevention of mental and emotional illnesses through research,training, and services. It is now one of the institutes of the Alcohol, Drug Abuse, and Mental Health Administration of the Department of Health, Education, and Welfare. Dr. Brown describes its continuous progress toward providing high-quality mental health care to the entire population, and discusses priorities for the future that include continuation of research on schizophrenia and depression and research that will benefit children and the elderly.", "contents": "The federal mental health program: past, present, and future. Dr. Brown traces the history of America's federal mental health program from its beginning in the early 1900s. NIMH, the institute he currently directs, was established in 1946 for the treatment and prevention of mental and emotional illnesses through research,training, and services. It is now one of the institutes of the Alcohol, Drug Abuse, and Mental Health Administration of the Department of Health, Education, and Welfare. Dr. Brown describes its continuous progress toward providing high-quality mental health care to the entire population, and discusses priorities for the future that include continuation of research on schizophrenia and depression and research that will benefit children and the elderly."} {"id": "PMID:179937", "title": "Homologous passive cutaneous anaphylaxis (PCA) in mice and heterologous PCA induced in rats with mouse IgE.", "content": "A study was made of the effect of anit-histamine, antiserotonin and of different anti-anaphylactic drugs on PCA reactions induced in mice with IgG1 or IgE. Further, using the ability of mouse IgE to sensitize rat mast cells, a comparative study was also made of PCA reactions induced in mice and rats with mouse IgE. Antihistamines produced a partial inhibition of PCA reactions induced in mice with mouse IgG1 or IgE and in rats with mouse IgE whereas antiserotonin inhibited PCA reactions induced in rats with mouse IgE, but had no effect on PCA reactions induced in mice with mouse IgG1 or IgE. The simultaneous use of antihistamine and antiserotonin resulted in a total inhibition of PCA reactions induced in mice with IgG1 and in a marked but not total inhibition of PCA reaction due to IgE; PCA reactions induced in rats with mouse IgE were totally inhibited. Compounds known to change the intracellular level of cyclic AMP were found to have little or no effect on PCA reactions induced in mice with either IgG1 or IgE in spite of producing a complete marked inhibition of PCA reactions induced with mouse IgE in rats. Diethylcarbamazine or disodium cromoglycate were also very effective inhibitors of rat PCA reactions induced with mouse IgE although having no effect on PCA reaction induced in mice with this same antibody or with IgG1. Thus, in spite of sharing common mediators released from the same type of target cell sensitized with the same type of antibody, PCA reactions induced in mice and rats with mouse IgE reacted very differently to the pharmacological effect of most of the drugs tested. This fact seems to indicate that the physiological mechanism operating in mouse mast cells are different from those operating in rat mast cells.", "contents": "Homologous passive cutaneous anaphylaxis (PCA) in mice and heterologous PCA induced in rats with mouse IgE. A study was made of the effect of anit-histamine, antiserotonin and of different anti-anaphylactic drugs on PCA reactions induced in mice with IgG1 or IgE. Further, using the ability of mouse IgE to sensitize rat mast cells, a comparative study was also made of PCA reactions induced in mice and rats with mouse IgE. Antihistamines produced a partial inhibition of PCA reactions induced in mice with mouse IgG1 or IgE and in rats with mouse IgE whereas antiserotonin inhibited PCA reactions induced in rats with mouse IgE, but had no effect on PCA reactions induced in mice with mouse IgG1 or IgE. The simultaneous use of antihistamine and antiserotonin resulted in a total inhibition of PCA reactions induced in mice with IgG1 and in a marked but not total inhibition of PCA reaction due to IgE; PCA reactions induced in rats with mouse IgE were totally inhibited. Compounds known to change the intracellular level of cyclic AMP were found to have little or no effect on PCA reactions induced in mice with either IgG1 or IgE in spite of producing a complete marked inhibition of PCA reactions induced with mouse IgE in rats. Diethylcarbamazine or disodium cromoglycate were also very effective inhibitors of rat PCA reactions induced with mouse IgE although having no effect on PCA reaction induced in mice with this same antibody or with IgG1. Thus, in spite of sharing common mediators released from the same type of target cell sensitized with the same type of antibody, PCA reactions induced in mice and rats with mouse IgE reacted very differently to the pharmacological effect of most of the drugs tested. This fact seems to indicate that the physiological mechanism operating in mouse mast cells are different from those operating in rat mast cells."} {"id": "PMID:179938", "title": "Rat IgE production. II. Primary and booster reaginic antibody responses following intradermal or oral immunization.", "content": "Primary and booster IgE antibody responses have been elicited in Hooded Lister rats by the intradermal injection or oral administration of very small quantities of egg albumin. Oral immunization was effected by giving antigen by stomach tube or in the drinking water. The minimum primary dose of antigen found to be effective was 1 mug intradermally and 10 mug orally, administered together with an intraperitoneal injection of B. pertussis adjuvant. In rats immunized with these doses secondary responses could be evoked by giving even smaller quantities of antigen, thus 1 ng intradermally or 1 mug orally without adjuvant. Smaller challenge doses were not tried. Large primary doses of antigen (greater than 100 mug) presented by these routes were, on the other hand, found to be inhibitory to the production of secondary IgE responses, this effect being similar to that observed in previously reported intraperitoneal immunization experiments. By contrast with previous experiments, however, tertiary responses could be obtained following immunization by these routes, and we believe this to be reflection of the absorption of smaller and therefore less inhibitory quantities of antigen. Our results are discussed in relation to the control of IgE antibody production, current concepts of the control of antigen absorption through mucosal barriers, and possible implications of the genesis of naturally occurring IgE responses in man.", "contents": "Rat IgE production. II. Primary and booster reaginic antibody responses following intradermal or oral immunization. Primary and booster IgE antibody responses have been elicited in Hooded Lister rats by the intradermal injection or oral administration of very small quantities of egg albumin. Oral immunization was effected by giving antigen by stomach tube or in the drinking water. The minimum primary dose of antigen found to be effective was 1 mug intradermally and 10 mug orally, administered together with an intraperitoneal injection of B. pertussis adjuvant. In rats immunized with these doses secondary responses could be evoked by giving even smaller quantities of antigen, thus 1 ng intradermally or 1 mug orally without adjuvant. Smaller challenge doses were not tried. Large primary doses of antigen (greater than 100 mug) presented by these routes were, on the other hand, found to be inhibitory to the production of secondary IgE responses, this effect being similar to that observed in previously reported intraperitoneal immunization experiments. By contrast with previous experiments, however, tertiary responses could be obtained following immunization by these routes, and we believe this to be reflection of the absorption of smaller and therefore less inhibitory quantities of antigen. Our results are discussed in relation to the control of IgE antibody production, current concepts of the control of antigen absorption through mucosal barriers, and possible implications of the genesis of naturally occurring IgE responses in man."} {"id": "PMID:179939", "title": "Production of circulating reaginic (IgE) antibodies by oral administration of ovalbumin to rats.", "content": "Reaginic antibody synthesis following parenteral and/or oral administration of ovalbumin and Bordetella pertussis organisms as adjuvant has been evaluated in LOU/M/Wsl inbred rats. These rats are able to produce high reaginic antibody serum levels after intraperitoneal injection of this antigen. Primary oral administration of ovalbumin doses between 10 and 100 mg with Bordetella pertussis organisms given as adjuvant by the intraperitoneal or the oral route led to characteristic reagnic responses. Secondary reaginic responses were obtained by oral administration of ovalbumin without any adjuvant in animals sensitized by the oral or the intraperitoneal route. A hundred micrograms of ovalbumin was enough to induce reaginic responses but more constant and higher reaginic levels were obtained with a 50 mg dose in the experimental model employed.", "contents": "Production of circulating reaginic (IgE) antibodies by oral administration of ovalbumin to rats. Reaginic antibody synthesis following parenteral and/or oral administration of ovalbumin and Bordetella pertussis organisms as adjuvant has been evaluated in LOU/M/Wsl inbred rats. These rats are able to produce high reaginic antibody serum levels after intraperitoneal injection of this antigen. Primary oral administration of ovalbumin doses between 10 and 100 mg with Bordetella pertussis organisms given as adjuvant by the intraperitoneal or the oral route led to characteristic reagnic responses. Secondary reaginic responses were obtained by oral administration of ovalbumin without any adjuvant in animals sensitized by the oral or the intraperitoneal route. A hundred micrograms of ovalbumin was enough to induce reaginic responses but more constant and higher reaginic levels were obtained with a 50 mg dose in the experimental model employed."} {"id": "PMID:179940", "title": "The differential effect of cyclic AMP on lymphocyte stimulation by T- or B-cell mitogens.", "content": "Dibutyryl-cyclic adenosine 3'5'-monophosphate (cAMP) added to mouse spleen cell cultures under serum free conditions inhibited the stimulation of [3H]thymidine incorporation induced by T-cell mitogens much more than the one induced by B-cell mitogens. The inhibition was most impressive with phytohaemagglutinin, followed by concanavalin A, pokeweed mitogen and the specific antigen Keyhole limpet haemocyanin (KLH). The response to bacterial lipopolysaccharide (LPS) was clearly less susceptible to suppression and the effect on the stimulation induced by trypsin and suramin, both B-cell mitogens, was marginal. Similar results were obtained by addition of isoproterenol or therophyllin to the cultures.", "contents": "The differential effect of cyclic AMP on lymphocyte stimulation by T- or B-cell mitogens. Dibutyryl-cyclic adenosine 3'5'-monophosphate (cAMP) added to mouse spleen cell cultures under serum free conditions inhibited the stimulation of [3H]thymidine incorporation induced by T-cell mitogens much more than the one induced by B-cell mitogens. The inhibition was most impressive with phytohaemagglutinin, followed by concanavalin A, pokeweed mitogen and the specific antigen Keyhole limpet haemocyanin (KLH). The response to bacterial lipopolysaccharide (LPS) was clearly less susceptible to suppression and the effect on the stimulation induced by trypsin and suramin, both B-cell mitogens, was marginal. Similar results were obtained by addition of isoproterenol or therophyllin to the cultures."} {"id": "PMID:179941", "title": "Two distinct lumphocyte-stimulating soluble factors (LAF) released from murine peritoneal cells. I. The cellular source and the effect of cGMP on their release.", "content": "Culture fluids of murine peritoneal cells contain two distinct, non-dialysable priniciples (LAF) with thymocyte proliferation-stimulating properties. One of them is elaborated from phagocytic cells (presumably macrophages), the other is released by non-phagocytic cells (lymphocytes). cGMP added exogenously stimulates the production and/or release of LAF from phagocytic cells, but not from non-phagocytic cells. The phagocytic cells (but not the lymphocytes) require intact RNA and protein synthesis for LAF release. The action of LAF differs from those of cGMP itself by being non-dialysable, and unable to prevent the inhibitory action of cAMP on mitogen-stimulated lymphocyte proliferation.", "contents": "Two distinct lumphocyte-stimulating soluble factors (LAF) released from murine peritoneal cells. I. The cellular source and the effect of cGMP on their release. Culture fluids of murine peritoneal cells contain two distinct, non-dialysable priniciples (LAF) with thymocyte proliferation-stimulating properties. One of them is elaborated from phagocytic cells (presumably macrophages), the other is released by non-phagocytic cells (lymphocytes). cGMP added exogenously stimulates the production and/or release of LAF from phagocytic cells, but not from non-phagocytic cells. The phagocytic cells (but not the lymphocytes) require intact RNA and protein synthesis for LAF release. The action of LAF differs from those of cGMP itself by being non-dialysable, and unable to prevent the inhibitory action of cAMP on mitogen-stimulated lymphocyte proliferation."} {"id": "PMID:179942", "title": "Quatification of phagocytosis by human neutrophils. The use of radiolabelled staphylococcal protein A-IgG complexes.", "content": "Human polymorphonuclear leucocytes suspended in a serum-free medium ingest radiolabelled insoluble staphylococcal protein A-IgG complexes, providing a quantitative measure of phagocytosis. The degree of uptake of protein A-IgG complexes is dependent on the cell concentration, the amount of immune precipitates and duration of incubation. The rate of phagocytosis is enhanced by the presence of serum. During the process of ingestion of immune precipitates, release of the lysosomal enzyme myeloperoxidase but not of the cytoplasmic enzyme lactic dehydrogenase occurs.", "contents": "Quatification of phagocytosis by human neutrophils. The use of radiolabelled staphylococcal protein A-IgG complexes. Human polymorphonuclear leucocytes suspended in a serum-free medium ingest radiolabelled insoluble staphylococcal protein A-IgG complexes, providing a quantitative measure of phagocytosis. The degree of uptake of protein A-IgG complexes is dependent on the cell concentration, the amount of immune precipitates and duration of incubation. The rate of phagocytosis is enhanced by the presence of serum. During the process of ingestion of immune precipitates, release of the lysosomal enzyme myeloperoxidase but not of the cytoplasmic enzyme lactic dehydrogenase occurs."} {"id": "PMID:179946", "title": "Marek's disease in chickens: development of viral antigen in feather follicles and of circulating antibodies.", "content": "The infection of young chickens with Marek's disease herpesvirus (MDHV) leads to the early appearance of viral antigen in the bursa Fabricii, in the kidney tubular epithelium, and particularly in the epithelial cells of growing feather follicles (Calnek and Hitchner, 1969; Purchase, 1970). Viral antigen may persist in feather follicles over several months, whereas in neural lesions or in lymphoid tumors induced by MDHV viral antigen is either lacking or present only in a few cells (Calnek and Hitchner, 1969; Spencer and Calnek, 1970; Purchase, 1970). Haider et al. (1976) have pointed out the high diagnostic value of the double-diffusion agar-gel participitation test (Chubb and Churchill, 1968) using growing feathers of MDHV-infected chickens as antigen.", "contents": "Marek's disease in chickens: development of viral antigen in feather follicles and of circulating antibodies. The infection of young chickens with Marek's disease herpesvirus (MDHV) leads to the early appearance of viral antigen in the bursa Fabricii, in the kidney tubular epithelium, and particularly in the epithelial cells of growing feather follicles (Calnek and Hitchner, 1969; Purchase, 1970). Viral antigen may persist in feather follicles over several months, whereas in neural lesions or in lymphoid tumors induced by MDHV viral antigen is either lacking or present only in a few cells (Calnek and Hitchner, 1969; Spencer and Calnek, 1970; Purchase, 1970). Haider et al. (1976) have pointed out the high diagnostic value of the double-diffusion agar-gel participitation test (Chubb and Churchill, 1968) using growing feathers of MDHV-infected chickens as antigen."} {"id": "PMID:179947", "title": "Some effects of silical treatment on Marek's disease.", "content": "Treatment of newly hatched chicks with silica by the intraperitoneal route delayed the onset of mortalities due to the JM strain of Marek's disease (MD' virus inoculated at 6 days of age. During the 88-day observation period fewer silica-treated chicks died of MD, but this difference was not usually statistically significant. Silica treatment had no effect on the susceptibility of 4-week-old birds. Silica treatment reduced the antibody response to MD but, in general, not significantly. The antibody response to bovine serum albumin was significantly enhanced if measured by the indirect hemagglutination test but not if measured by the agar gel diffusion test, whereas the response to Brucella abortus was enhanced significantly in N-line (MD-resistant) chicks but not significantly in P-line (MD-susceptible) chicks. Five days after infection, silica-treated chicks had significantly less fluorescing antigen in thymus and bursa than did untreated chicks; no difference was observed in the spleen. After silica treatment the glass-adherent cell population in the buffy coat was increased by up to 10-fold compared with untreated chicks. It is suggested that silica treatment induced macrophage proliferation, with subsequent restriction of MD virus spread, yet allowed an adjuvant-type effect with other antigens.", "contents": "Some effects of silical treatment on Marek's disease. Treatment of newly hatched chicks with silica by the intraperitoneal route delayed the onset of mortalities due to the JM strain of Marek's disease (MD' virus inoculated at 6 days of age. During the 88-day observation period fewer silica-treated chicks died of MD, but this difference was not usually statistically significant. Silica treatment had no effect on the susceptibility of 4-week-old birds. Silica treatment reduced the antibody response to MD but, in general, not significantly. The antibody response to bovine serum albumin was significantly enhanced if measured by the indirect hemagglutination test but not if measured by the agar gel diffusion test, whereas the response to Brucella abortus was enhanced significantly in N-line (MD-resistant) chicks but not significantly in P-line (MD-susceptible) chicks. Five days after infection, silica-treated chicks had significantly less fluorescing antigen in thymus and bursa than did untreated chicks; no difference was observed in the spleen. After silica treatment the glass-adherent cell population in the buffy coat was increased by up to 10-fold compared with untreated chicks. It is suggested that silica treatment induced macrophage proliferation, with subsequent restriction of MD virus spread, yet allowed an adjuvant-type effect with other antigens."} {"id": "PMID:179948", "title": "Genetic control of natural immunity to ecotropic mouse leukemia viruses: production of endogenous immunogen.", "content": "Mice of the AKR and C57L strains naturally produced low titers of antibody against ecotropic murine leukemia viruses (MuLV). The F1 hybrid of these strains produced anti-MuLV antibody in higher titer than mice of either of the parental strains. Progeny of the genetic backcross C57L X (AKR X C57L)F1 segregated for the production of infectious ecotropic MuLV (according to the Akv-1 and Akv-2 loci) and for the production of antibody against MuLV. All mice that contained infectious MuLV produced anti-MuLV antibodies. Thus, the persistent production of high-titered MuLV in these mice did not result in immunological tolerance towards viral antigens. In contrast, mice that did not contain infectious MuLV could be separated into antibody-producing and -nonproducing classes. The absence of detectable antibody to MuLV in an individual mouse was invariably associated with a virus-free phenotype. Antibody against MuLV reacted primarily with p15 and gp70 proteins of the viral envelope. It was concluded that overt production of endogenous ecotropic MuLV served as a major immunogenic stimulus for the production of anti-MuLV antibody in these mice.", "contents": "Genetic control of natural immunity to ecotropic mouse leukemia viruses: production of endogenous immunogen. Mice of the AKR and C57L strains naturally produced low titers of antibody against ecotropic murine leukemia viruses (MuLV). The F1 hybrid of these strains produced anti-MuLV antibody in higher titer than mice of either of the parental strains. Progeny of the genetic backcross C57L X (AKR X C57L)F1 segregated for the production of infectious ecotropic MuLV (according to the Akv-1 and Akv-2 loci) and for the production of antibody against MuLV. All mice that contained infectious MuLV produced anti-MuLV antibodies. Thus, the persistent production of high-titered MuLV in these mice did not result in immunological tolerance towards viral antigens. In contrast, mice that did not contain infectious MuLV could be separated into antibody-producing and -nonproducing classes. The absence of detectable antibody to MuLV in an individual mouse was invariably associated with a virus-free phenotype. Antibody against MuLV reacted primarily with p15 and gp70 proteins of the viral envelope. It was concluded that overt production of endogenous ecotropic MuLV served as a major immunogenic stimulus for the production of anti-MuLV antibody in these mice."} {"id": "PMID:179949", "title": "Genetic control of natural immunity to ecotropic mouse leukemia viruses: immune response genes.", "content": "Humoral immune response to ectropic leukemia viruses in AKR and C57BL/6 mice was controlled by a gene that mapped in linkage group IX. Mice of the AKR strain had an immune nonresponsive allele of this gene, whereas mice of the C57BL/6 strain had an immune responsive allele. Antibody against murine leukemia virus (MuLV) reacted primarily with p15 protein of the viral envelope. It was concluded that the failure to find antibody production in AKR mice was the result of a genetic immunological defect, rather than the result of immunological tolerance that was induced by the persistent viremia of endogenous MuLV.", "contents": "Genetic control of natural immunity to ecotropic mouse leukemia viruses: immune response genes. Humoral immune response to ectropic leukemia viruses in AKR and C57BL/6 mice was controlled by a gene that mapped in linkage group IX. Mice of the AKR strain had an immune nonresponsive allele of this gene, whereas mice of the C57BL/6 strain had an immune responsive allele. Antibody against murine leukemia virus (MuLV) reacted primarily with p15 protein of the viral envelope. It was concluded that the failure to find antibody production in AKR mice was the result of a genetic immunological defect, rather than the result of immunological tolerance that was induced by the persistent viremia of endogenous MuLV."} {"id": "PMID:179950", "title": "Interaction of Chlamydia trachomatis organisms and HeLa 229 cells.", "content": "The infection of HeLa 229 cells in monolayer culture with trachoma (B/TW-5/OT) and lymphogranuloma venereum (LGV) (L2/434/Bu) organism was studied in terms of two parameters: radioactivity counts of cell-associated tritium labeled organisms at the initial stage of inoculation for measurement of attachment, and inclusion counts of infection cells after incubation for measurement of growth. Factors affecting attachment and inclusion formation and correlation of the two are presented. It was shown that attachment is an important initial step in infection by Chlamydia trachomatis. The rate of attachment was temperature dependent. The attachment of LGV organisms was affected more profoundly by temperature than was that of trachoma organisms. Attachment and inclusion formation of trachoma and LGV organisms were inhibited by heparin. Diethylaminoethyl-dextran was again shown to enhance attachment and inclusion formation of trachoma but not LGV organisms. NaF had no effect on attachment, but inhibited inclusion formation of both trachoma and LGV organisms. Both attachment and inclusion formation of trachoma organisms were strongly enhanced by centrifugation of the inoculum onto the cell monolayer. Although inclusion formation of trachoma organism was much greater in susceptible cells (HeLa 229) than relatively insusceptible cells (fetal tonsil), attachment was only slightly greater. The results based on the test of two cell lines suggested that attachment prpbably is not a critical factor in determing a cell line's susceptibility to infection with trachoma organisms.", "contents": "Interaction of Chlamydia trachomatis organisms and HeLa 229 cells. The infection of HeLa 229 cells in monolayer culture with trachoma (B/TW-5/OT) and lymphogranuloma venereum (LGV) (L2/434/Bu) organism was studied in terms of two parameters: radioactivity counts of cell-associated tritium labeled organisms at the initial stage of inoculation for measurement of attachment, and inclusion counts of infection cells after incubation for measurement of growth. Factors affecting attachment and inclusion formation and correlation of the two are presented. It was shown that attachment is an important initial step in infection by Chlamydia trachomatis. The rate of attachment was temperature dependent. The attachment of LGV organisms was affected more profoundly by temperature than was that of trachoma organisms. Attachment and inclusion formation of trachoma and LGV organisms were inhibited by heparin. Diethylaminoethyl-dextran was again shown to enhance attachment and inclusion formation of trachoma but not LGV organisms. NaF had no effect on attachment, but inhibited inclusion formation of both trachoma and LGV organisms. Both attachment and inclusion formation of trachoma organisms were strongly enhanced by centrifugation of the inoculum onto the cell monolayer. Although inclusion formation of trachoma organism was much greater in susceptible cells (HeLa 229) than relatively insusceptible cells (fetal tonsil), attachment was only slightly greater. The results based on the test of two cell lines suggested that attachment prpbably is not a critical factor in determing a cell line's susceptibility to infection with trachoma organisms."} {"id": "PMID:179951", "title": "Quantitation of antibody to hepatitis A antigen by immune electron microscopy.", "content": "A set of precipitin reactions was performed by immune electron microscopy (IEM) with hepatitis A antigen (HA Ag) and varying quantities of antibody to HA A q (anti-HA). Serial dilution of anti-HA resulted in progressive diminution in IEM antibody rating. These data, together with a highly significant correlation between IEM ratings and immune adherence hemagglutination (IAHA) titers on 92 coded serum samples, confirm that quantitative serology development can be performed by IEM. To demonstrate the different kinetics of antibody development by IEM and IAHA, we used both techniques to test for anti-HA in longitudinally collected sera from a chimpanzee experimentally infected with hepatitis A virus. Detection of anti-HA was possible by IEM during acute hepatitis, but IAHA anti-HA was not observed until approximately 4 weeks later. Six weeks after acute illness, IEM ratings reached a plateau beyond which IAHA titers continued to rise gradually. Peak titers were achieved 11 months after inoculation.", "contents": "Quantitation of antibody to hepatitis A antigen by immune electron microscopy. A set of precipitin reactions was performed by immune electron microscopy (IEM) with hepatitis A antigen (HA Ag) and varying quantities of antibody to HA A q (anti-HA). Serial dilution of anti-HA resulted in progressive diminution in IEM antibody rating. These data, together with a highly significant correlation between IEM ratings and immune adherence hemagglutination (IAHA) titers on 92 coded serum samples, confirm that quantitative serology development can be performed by IEM. To demonstrate the different kinetics of antibody development by IEM and IAHA, we used both techniques to test for anti-HA in longitudinally collected sera from a chimpanzee experimentally infected with hepatitis A virus. Detection of anti-HA was possible by IEM during acute hepatitis, but IAHA anti-HA was not observed until approximately 4 weeks later. Six weeks after acute illness, IEM ratings reached a plateau beyond which IAHA titers continued to rise gradually. Peak titers were achieved 11 months after inoculation."} {"id": "PMID:179952", "title": "Vaccinia virus meningitis in mice after intracerebral inoculation.", "content": "The pathogenesis of experimental vaccinia virus infection in weanling mice after intracerebral inoculation was followed with virological, histological, and immunohistological methods. High-dose inoculation, virus spread from brain to thoracic and abdominal viscera probably by an undetected early viremia. Virus did rise to detectable levels in blood by day 5 and was found to be associated with the mononuclear cell fraction. By day 12, 30% of the animals had died and no further deaths occurred. Rise of neutralizing antibody correlated with disappearance of cell-free virus in blood, brain, and viscera. Virus was present in the brains of animals for 20 days after inoculation. This animal model may be useful to study mechanisms of persistent central nervous system virus disease relevant to man.", "contents": "Vaccinia virus meningitis in mice after intracerebral inoculation. The pathogenesis of experimental vaccinia virus infection in weanling mice after intracerebral inoculation was followed with virological, histological, and immunohistological methods. High-dose inoculation, virus spread from brain to thoracic and abdominal viscera probably by an undetected early viremia. Virus did rise to detectable levels in blood by day 5 and was found to be associated with the mononuclear cell fraction. By day 12, 30% of the animals had died and no further deaths occurred. Rise of neutralizing antibody correlated with disappearance of cell-free virus in blood, brain, and viscera. Virus was present in the brains of animals for 20 days after inoculation. This animal model may be useful to study mechanisms of persistent central nervous system virus disease relevant to man."} {"id": "PMID:179953", "title": "Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus.", "content": "The pathogenicity of infection produced following intracerebral (i.c.) inoculation of wild-type vesicular stomatitis virus (VSV) or temperature-sensitive (ts) mutants of VSV was compared. ts mutants used were ts 31 (VSV complementation group II) and ts 41 (VSV complementation group IV). The i.c. injection of wild-type VSV in weanling Swiss mice produced a rapidly fatal encephalitis with death of mice in 2 to 3 days. Histopathologically, such mice exhibited minimal changes of encephalitis on light microscopy. In contrast to the highly virulent, rapidly fatal central nervous system (CNS) infection seen after i.c. inoculation of wild-type VSV, infection with ts 31 VSV produced a more slowly progressive CNS infection characterized by hind limb paralysis and death 6 to 9 days after infection. Histopathologically, CNS infection with ts 31 is associated with previously unreported extensive spongiform changes in the gray matter of the spinal cord. The inoculation of ts 41 i.c., on the other hand, did not result in either clinical illness or histopathological changes in the spinal cords or brains of infected mice. The absence of clinical and histopathological lesions following i.c. infection of ts 41 VSV suggests that the capacity to alter the pathogenesis of VSV CNS infection may be a function of only certain ts mutants of VSV.", "contents": "Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus. The pathogenicity of infection produced following intracerebral (i.c.) inoculation of wild-type vesicular stomatitis virus (VSV) or temperature-sensitive (ts) mutants of VSV was compared. ts mutants used were ts 31 (VSV complementation group II) and ts 41 (VSV complementation group IV). The i.c. injection of wild-type VSV in weanling Swiss mice produced a rapidly fatal encephalitis with death of mice in 2 to 3 days. Histopathologically, such mice exhibited minimal changes of encephalitis on light microscopy. In contrast to the highly virulent, rapidly fatal central nervous system (CNS) infection seen after i.c. inoculation of wild-type VSV, infection with ts 31 VSV produced a more slowly progressive CNS infection characterized by hind limb paralysis and death 6 to 9 days after infection. Histopathologically, CNS infection with ts 31 is associated with previously unreported extensive spongiform changes in the gray matter of the spinal cord. The inoculation of ts 41 i.c., on the other hand, did not result in either clinical illness or histopathological changes in the spinal cords or brains of infected mice. The absence of clinical and histopathological lesions following i.c. infection of ts 41 VSV suggests that the capacity to alter the pathogenesis of VSV CNS infection may be a function of only certain ts mutants of VSV."} {"id": "PMID:179954", "title": "The binding properties of rabbit antibodies against various penicillins as studied by immunoprecipitation, indirect haemagglutination and radiometric immunoassay.", "content": "Rabbit antibodies raised against protein conjugates of azidocillin (AzO), ampicillin (AmpO), benzylpenicillin (BPO) and crude 6-aminopenicillanic acid (6-APA) gave rise to two precipitation lines in immunoprecipitation tests against penicillin protein conjugates where the carrier was unrelated to the immunogens. This pattern verifies extensive cross-reactions between penicillins, which have previously been reported. The use of AzO-coated rabbit red cells in indirect haemagglutination (IHA) inhibition tests showed good reactivity (a) between the inhibitor AzO and antibodies raised against AzO, AmpO and BPO, (b) between the inhibitor AmpO and antibodies raised against AmpO and BPO, (c) between the inhibitor BPO and antibodies raised against BPO. When BPO-coated red cells were used, AzO, AmpO and BPO inhibited the IHA activity of antibodies against the BPO. Varying IHA results were obtained using differently conjugated rabbit red cells. Thus antibodies against AmpO gave higher titres when using AzO- than BPO-coated red cells while for antibodies against BPO the opposite was noted. The radiometric assay utilizing AzO-serum albumin as tracer as well as reference substance resulted in significantly higher values for antisera against AzO and AmpO compared with those for antisera against crude 6-APA. Antisera against BPO were not analysed in this respect. Furthermore, there was poor correlation between the results obtained with the indirect IHA technique and the radiometric immunoassay.", "contents": "The binding properties of rabbit antibodies against various penicillins as studied by immunoprecipitation, indirect haemagglutination and radiometric immunoassay. Rabbit antibodies raised against protein conjugates of azidocillin (AzO), ampicillin (AmpO), benzylpenicillin (BPO) and crude 6-aminopenicillanic acid (6-APA) gave rise to two precipitation lines in immunoprecipitation tests against penicillin protein conjugates where the carrier was unrelated to the immunogens. This pattern verifies extensive cross-reactions between penicillins, which have previously been reported. The use of AzO-coated rabbit red cells in indirect haemagglutination (IHA) inhibition tests showed good reactivity (a) between the inhibitor AzO and antibodies raised against AzO, AmpO and BPO, (b) between the inhibitor AmpO and antibodies raised against AmpO and BPO, (c) between the inhibitor BPO and antibodies raised against BPO. When BPO-coated red cells were used, AzO, AmpO and BPO inhibited the IHA activity of antibodies against the BPO. Varying IHA results were obtained using differently conjugated rabbit red cells. Thus antibodies against AmpO gave higher titres when using AzO- than BPO-coated red cells while for antibodies against BPO the opposite was noted. The radiometric assay utilizing AzO-serum albumin as tracer as well as reference substance resulted in significantly higher values for antisera against AzO and AmpO compared with those for antisera against crude 6-APA. Antisera against BPO were not analysed in this respect. Furthermore, there was poor correlation between the results obtained with the indirect IHA technique and the radiometric immunoassay."} {"id": "PMID:179955", "title": "Differential induction of Epstein-Barr virus-related antigens in human lymphoblastoid cells by virus-mediated cell-to-cell contact.", "content": "Differential induction of Epstein-Barr virus (EBV)-related antigens was observed after Sendai virus-medicated fusion of producer and non-producer cells with various human and mouse cells. The EBV-determined early nuclear antigen (ENA), early antigen (EA) and viral capsid antigen (VCA) could be induced at a high rate in producer cells (P3HR-1 and B95-8), normally expressing these antigens at very low frequency, as early as 12-24 h after fusion with each other or with human amnion FL cells. In contrast, only one antigen, ENA, was induced in producer cells following fusion with non-producer cells. This limited induction occurred also in non-producer cells fused with FL cells, but not after fusion with each other. EBV induction did not result from fusion of either producer or non-producer cells with mouse cells (L-M (TK-) Cl1D and MCB-L). The differential induction was not the result of heterokaryon formation as determined by autoradiography. The implications of these findings are discussed.", "contents": "Differential induction of Epstein-Barr virus-related antigens in human lymphoblastoid cells by virus-mediated cell-to-cell contact. Differential induction of Epstein-Barr virus (EBV)-related antigens was observed after Sendai virus-medicated fusion of producer and non-producer cells with various human and mouse cells. The EBV-determined early nuclear antigen (ENA), early antigen (EA) and viral capsid antigen (VCA) could be induced at a high rate in producer cells (P3HR-1 and B95-8), normally expressing these antigens at very low frequency, as early as 12-24 h after fusion with each other or with human amnion FL cells. In contrast, only one antigen, ENA, was induced in producer cells following fusion with non-producer cells. This limited induction occurred also in non-producer cells fused with FL cells, but not after fusion with each other. EBV induction did not result from fusion of either producer or non-producer cells with mouse cells (L-M (TK-) Cl1D and MCB-L). The differential induction was not the result of heterokaryon formation as determined by autoradiography. The implications of these findings are discussed."} {"id": "PMID:179956", "title": "RNA associated with non-histone chromosomal proteins in rat liver and in ascites hepatoma.", "content": "The purpose of the experiments was to determine if changes in the post-transcriptional processing of RNA in the hepatoma also affect the low molecular weight nuclear RNA which is transcribed from families of related genes and associated with non-histone chromosomal proteins. Separation of non-histone chromosomal proteins on Sephadex G-200 into three fractions separated the low molecular weight RNA associated with these proteins into metabolically stable RNA firmly bound to the first eluted fractions of high molecular weight non-histone chromosomal proteins, and into a metabolically active RNA which is eluted with the third protein fraction and can be separated from the low molecular weight non-histone chromosomal proteins by chromatography on DEAE-Sephadex A 25 (fraction III RNA). In liver as well as in hepatoma, this fraction III RNA represents about 50% of the RNA associated with the non-histone chromosomal proteins. Fraction III RNA from both tissues has an approximate molecular weight of 13,000, is rich in guanylic acid, is lacking dihydropyrimidines and is copied from the repetitive sequences of DNA. The content of uridylic acid is much higher in fraction III RNA isolated from hepatoma than in the same RNA isolated from liver, and competitive hybridization has shown that hepatoma fraction III RNA contains not only new base sequences which are not present in liver fraction III RNA, but also lacks some sequences which are present in the liver RNA. The technique of RNA/DNA hybridization in the presence of competing RNA has shown that, in hepatoma, the cytoplasmic RNA competes with more than 60% of the fraction III RNA for the hybridization sites on repetitive DNA. No competition was found when liver cytoplasmic RNA was used. The low ratio of competing hepatoma cytoplasmic RNA or of liver or hepatoma nuclear RNA which is required to displace fraction III RNA from its hybridization with DNA indicates that this RNA is synthesized and in hepatoma is also released into the cytoplasm as a part of larger RNA molecules. The detection of the nucleotide sequences found in liver associated with non-histone chromosomal proteins in the cytoplasm of hepatoma cells is evidence for extensive disruption of the post-transcriptional control in hepatoma.", "contents": "RNA associated with non-histone chromosomal proteins in rat liver and in ascites hepatoma. The purpose of the experiments was to determine if changes in the post-transcriptional processing of RNA in the hepatoma also affect the low molecular weight nuclear RNA which is transcribed from families of related genes and associated with non-histone chromosomal proteins. Separation of non-histone chromosomal proteins on Sephadex G-200 into three fractions separated the low molecular weight RNA associated with these proteins into metabolically stable RNA firmly bound to the first eluted fractions of high molecular weight non-histone chromosomal proteins, and into a metabolically active RNA which is eluted with the third protein fraction and can be separated from the low molecular weight non-histone chromosomal proteins by chromatography on DEAE-Sephadex A 25 (fraction III RNA). In liver as well as in hepatoma, this fraction III RNA represents about 50% of the RNA associated with the non-histone chromosomal proteins. Fraction III RNA from both tissues has an approximate molecular weight of 13,000, is rich in guanylic acid, is lacking dihydropyrimidines and is copied from the repetitive sequences of DNA. The content of uridylic acid is much higher in fraction III RNA isolated from hepatoma than in the same RNA isolated from liver, and competitive hybridization has shown that hepatoma fraction III RNA contains not only new base sequences which are not present in liver fraction III RNA, but also lacks some sequences which are present in the liver RNA. The technique of RNA/DNA hybridization in the presence of competing RNA has shown that, in hepatoma, the cytoplasmic RNA competes with more than 60% of the fraction III RNA for the hybridization sites on repetitive DNA. No competition was found when liver cytoplasmic RNA was used. The low ratio of competing hepatoma cytoplasmic RNA or of liver or hepatoma nuclear RNA which is required to displace fraction III RNA from its hybridization with DNA indicates that this RNA is synthesized and in hepatoma is also released into the cytoplasm as a part of larger RNA molecules. The detection of the nucleotide sequences found in liver associated with non-histone chromosomal proteins in the cytoplasm of hepatoma cells is evidence for extensive disruption of the post-transcriptional control in hepatoma."} {"id": "PMID:179957", "title": "The detection of virus DNA sequences in a herpes type 2 transformed hamster cell line (333-8-9).", "content": "Herpes simplex virus type 2 DNA labelled in vitro with 125I has been used as a probe to search for virus DNA sequences in the 333-8-9 line of transformed primary hamster cells and in clines derived from the line. Virus DNA sequences were present when the cells were examined initially but these sequences were lost on subsequent handling. No virus sequences were detected in clones derived from the line. It is suggested that the presence of virus DNA is an unstable characteristic of the cell line and that these sequences may be lost at cell division. The possibility that a small fragment of the genome remains cannot be excluded.", "contents": "The detection of virus DNA sequences in a herpes type 2 transformed hamster cell line (333-8-9). Herpes simplex virus type 2 DNA labelled in vitro with 125I has been used as a probe to search for virus DNA sequences in the 333-8-9 line of transformed primary hamster cells and in clines derived from the line. Virus DNA sequences were present when the cells were examined initially but these sequences were lost on subsequent handling. No virus sequences were detected in clones derived from the line. It is suggested that the presence of virus DNA is an unstable characteristic of the cell line and that these sequences may be lost at cell division. The possibility that a small fragment of the genome remains cannot be excluded."} {"id": "PMID:179958", "title": "Clonal derivatives of a herpes type 2 transformed hamster cell line (333-8-9): cytogenetic analysis, tumorigenicity and virus sequence detection.", "content": "The characteristics of the Syrian hamster cell line (333-8-9), putatively transformed by herpes virus type 2 (HSV-2), strain 333, have been examined. The line has been cloned and the clones characterized cytogenetically and morphologically. The original line and the clones have been assayed for tumorigenicity and for the presence of herpes-virus-specific nucleic acid sequences using in situ hybridization with 125I HSV-2 DNA. The line 333-8-9 is hyperdiploid with a mode of 49 chromosomes and contains a spectrum of cytogenetic marker chromosomes present in varying frequencies. The clones demonstrate a segregation of these marker chromosomes and other abnormal chromosomes. Cloned lines have distinct stem-cell types with the characteristic abnormal chromosomes present in a high percentage of cells. Some of the marker chromosomes have been identified by Giemsa banding techniques. All the clones have distinctive, persistent in vitro morphologies, ranging from purely epithelial to purely fibroblastic. They differ from the line 333-8-9 and between themselves in tumorigenicity, varying from highly tumorigenic to entirely non-tumorigenic. Herpes virus 2 specific sequences have been detected in the original cell line and in all but two of the clones. There does not appear to be any obvious correlation between the three parameters of: (1) detection of HSV-2 information; (2) marker chromosome occurrence; and (3) tumorigenicity.", "contents": "Clonal derivatives of a herpes type 2 transformed hamster cell line (333-8-9): cytogenetic analysis, tumorigenicity and virus sequence detection. The characteristics of the Syrian hamster cell line (333-8-9), putatively transformed by herpes virus type 2 (HSV-2), strain 333, have been examined. The line has been cloned and the clones characterized cytogenetically and morphologically. The original line and the clones have been assayed for tumorigenicity and for the presence of herpes-virus-specific nucleic acid sequences using in situ hybridization with 125I HSV-2 DNA. The line 333-8-9 is hyperdiploid with a mode of 49 chromosomes and contains a spectrum of cytogenetic marker chromosomes present in varying frequencies. The clones demonstrate a segregation of these marker chromosomes and other abnormal chromosomes. Cloned lines have distinct stem-cell types with the characteristic abnormal chromosomes present in a high percentage of cells. Some of the marker chromosomes have been identified by Giemsa banding techniques. All the clones have distinctive, persistent in vitro morphologies, ranging from purely epithelial to purely fibroblastic. They differ from the line 333-8-9 and between themselves in tumorigenicity, varying from highly tumorigenic to entirely non-tumorigenic. Herpes virus 2 specific sequences have been detected in the original cell line and in all but two of the clones. There does not appear to be any obvious correlation between the three parameters of: (1) detection of HSV-2 information; (2) marker chromosome occurrence; and (3) tumorigenicity."} {"id": "PMID:179959", "title": "Characterization of an early cytotoxicity-inducing factor in sera of Japanese quails after inoculation with Rous sarcoma virus.", "content": "By pre-treatment with serum of normal spleen cells used in the microcytotoxicity assay, a humoral factor which induces cytotoxic activity in normal spleen cells was demonstrated in about 40% of sera of Japanese quails as early as 3 days after inoculation with Rous sarcoma virus (RSV). This cytotoxicity-inducing activity was not present either in the IgM or the IgG fraction obtained by Sephadex gel filtration. In sera of quails with experimentally induced agammaglobulinemia, the cytotoxicity-inducing activity was demonstrated at the same frequency as in normal animals. Thus, it seems unlikely that the early cytotoxicity-inducing factor is an immunoglobulin. On the other hand, membrane fractions extracted with 3 M potassium chloride from the RSV-induced quail tumor (QT) cells used as target cells in the microcytotoxicity assay exhibited cytotoxicity-inducing activity. After spontaneous regression of an RSV-induced tumor the serum of the regressor quail contained antibodies specific to the QT cell extract. This serum removed the cytotoxicity-inducing activity of both QT cell extract and serum sampled 3 days after RSV inoculation. In contrast, serum without antibody to the QT cell extract failed to absorb the cytotoxicity-inducing activity of the extract. It is therefore suggested that soluble tumor antigens can act as an early cytotoxicity-inducing factor.", "contents": "Characterization of an early cytotoxicity-inducing factor in sera of Japanese quails after inoculation with Rous sarcoma virus. By pre-treatment with serum of normal spleen cells used in the microcytotoxicity assay, a humoral factor which induces cytotoxic activity in normal spleen cells was demonstrated in about 40% of sera of Japanese quails as early as 3 days after inoculation with Rous sarcoma virus (RSV). This cytotoxicity-inducing activity was not present either in the IgM or the IgG fraction obtained by Sephadex gel filtration. In sera of quails with experimentally induced agammaglobulinemia, the cytotoxicity-inducing activity was demonstrated at the same frequency as in normal animals. Thus, it seems unlikely that the early cytotoxicity-inducing factor is an immunoglobulin. On the other hand, membrane fractions extracted with 3 M potassium chloride from the RSV-induced quail tumor (QT) cells used as target cells in the microcytotoxicity assay exhibited cytotoxicity-inducing activity. After spontaneous regression of an RSV-induced tumor the serum of the regressor quail contained antibodies specific to the QT cell extract. This serum removed the cytotoxicity-inducing activity of both QT cell extract and serum sampled 3 days after RSV inoculation. In contrast, serum without antibody to the QT cell extract failed to absorb the cytotoxicity-inducing activity of the extract. It is therefore suggested that soluble tumor antigens can act as an early cytotoxicity-inducing factor."} {"id": "PMID:179960", "title": "Tumorigenicity of Epstein-Barr virus (EBV)-transformed lymphoid line cells in autologous squirrel monkeys.", "content": "Eight squirrel monkeys (Saimiri sciureus) challenged with EBV or EBV-transformed SLCL were naturally or experimentally infected with Plasmodium knowlesi or Pl. brasilianum. Most of the animals had been splenectomized and unilaterally nephrectomized. Three of these monkeys received one dose of 6 to 12 X 10(8) autologous SLCL. These lines were derived from saimiri lymphoid cells permanently transformed by B-EBV in vitro. All three animals developed multiple undifferentiated malignant lymphomas and died 8 to 10 days post inoculation. Necropsy tumor specimens were EBNA-positive and contained 7 to 21 EBV genome equivalents per cell. EBNA- and EA-positive SLCL were established in vitro from four tumor explants of two monkeys. These results demonstrate that in vitro EBV-transformed SLCL are able to cause tumor formation in autologous squirrel monkeys. Five monkeys received high transforming doses of B-EBV or S-EBV, derived from one of the tumorigenic SLCL. None of the animals developed any sign of tumor formation during an observation period of up to 130 days. Three of these monkeys showed no detectable EBV-related seroconversion while the sera of two monkeys had become anti-EBNA-positive when tested at days 28 and 130 respectively post inoculation. Two additional monkeys received neither EBV nor SLCL. They showed no clinical evidence of tumor development or spontaneous seroconversion over a period of more than 1 year.", "contents": "Tumorigenicity of Epstein-Barr virus (EBV)-transformed lymphoid line cells in autologous squirrel monkeys. Eight squirrel monkeys (Saimiri sciureus) challenged with EBV or EBV-transformed SLCL were naturally or experimentally infected with Plasmodium knowlesi or Pl. brasilianum. Most of the animals had been splenectomized and unilaterally nephrectomized. Three of these monkeys received one dose of 6 to 12 X 10(8) autologous SLCL. These lines were derived from saimiri lymphoid cells permanently transformed by B-EBV in vitro. All three animals developed multiple undifferentiated malignant lymphomas and died 8 to 10 days post inoculation. Necropsy tumor specimens were EBNA-positive and contained 7 to 21 EBV genome equivalents per cell. EBNA- and EA-positive SLCL were established in vitro from four tumor explants of two monkeys. These results demonstrate that in vitro EBV-transformed SLCL are able to cause tumor formation in autologous squirrel monkeys. Five monkeys received high transforming doses of B-EBV or S-EBV, derived from one of the tumorigenic SLCL. None of the animals developed any sign of tumor formation during an observation period of up to 130 days. Three of these monkeys showed no detectable EBV-related seroconversion while the sera of two monkeys had become anti-EBNA-positive when tested at days 28 and 130 respectively post inoculation. Two additional monkeys received neither EBV nor SLCL. They showed no clinical evidence of tumor development or spontaneous seroconversion over a period of more than 1 year."} {"id": "PMID:179962", "title": "N-acetylserine in horse muscle acylphosphatase.", "content": "A ninhydrin-negative peptide fraction obtained from tryptic digest of carboxymethyl acylphosphatase was isolated by chromatography on a column of PA 28 Beckman resin and analysed for the amino acid composition. Degradation with carboxypeptidase B and A indicated that the sequence of this peptide was: X-Thr-Ala-Arg. The amino-terminal residue was identified as N-acetylserine by high voltage electrophoresis. It is therefore suggested that the sequence of the NH2-terminal portion of CM-acylphosphatase is N-acetyl-Ser-Thr-Ala-Arg. Digestion with carboxypeptidase A and B indicated also that the COOH-terminal portion of CM-acylphosphatase is-Arg-Tyr-OH.", "contents": "N-acetylserine in horse muscle acylphosphatase. A ninhydrin-negative peptide fraction obtained from tryptic digest of carboxymethyl acylphosphatase was isolated by chromatography on a column of PA 28 Beckman resin and analysed for the amino acid composition. Degradation with carboxypeptidase B and A indicated that the sequence of this peptide was: X-Thr-Ala-Arg. The amino-terminal residue was identified as N-acetylserine by high voltage electrophoresis. It is therefore suggested that the sequence of the NH2-terminal portion of CM-acylphosphatase is N-acetyl-Ser-Thr-Ala-Arg. Digestion with carboxypeptidase A and B indicated also that the COOH-terminal portion of CM-acylphosphatase is-Arg-Tyr-OH."} {"id": "PMID:179963", "title": "Appearance of Epstein-Barr virus-determined nuclear antigen in human epithelial cells following fusion with lymphoid cells.", "content": "When human epithelial FL cells were fused with lymphoid cells harboring Epstein-Barr virus (EBV) genome, EBV-determined nuclear antigen (EBNA) immunofluorescence became evident in high frequency in FL nuclei of heterokaryons several days after fusion. The implications of the findings are discussed in relation to the presence of EBV genome in nasopharyngeal carcinoma cells.", "contents": "Appearance of Epstein-Barr virus-determined nuclear antigen in human epithelial cells following fusion with lymphoid cells. When human epithelial FL cells were fused with lymphoid cells harboring Epstein-Barr virus (EBV) genome, EBV-determined nuclear antigen (EBNA) immunofluorescence became evident in high frequency in FL nuclei of heterokaryons several days after fusion. The implications of the findings are discussed in relation to the presence of EBV genome in nasopharyngeal carcinoma cells."} {"id": "PMID:179968", "title": "The effect of culture on ultrastructure of dissociated rabbit adenohypophysial cells.", "content": "Cells from the rabbit pars distalis and pars intermedia have been cultured in several ways. In clump cultures the glandular adenohypophysial cells of the primary clump remain identifiable for long periods. Both acidophil and mucoid cells can be maintained in this way for over 50 days. During this time two different modes of granule extrusion are observed, one being found only in acidophil cells and the other being exclusive to mucoid cells. From this it is concluded that specific release of secretory products from these cells can occur in the absence of hypothalmic control. A special form of collagenous fibre is produced in clump cultures. Monolayer cell cultures are derived either from isolated adenohypophysial cells or from secondarily aggregated clumps, but in either case the predominant cells are fibroblasts, which persist for over 50 days (as isolated cultures) and for over 90 days (as spreads from clumps). Rounded cells can be recognized as a separate type in isolated cell culture.", "contents": "The effect of culture on ultrastructure of dissociated rabbit adenohypophysial cells. Cells from the rabbit pars distalis and pars intermedia have been cultured in several ways. In clump cultures the glandular adenohypophysial cells of the primary clump remain identifiable for long periods. Both acidophil and mucoid cells can be maintained in this way for over 50 days. During this time two different modes of granule extrusion are observed, one being found only in acidophil cells and the other being exclusive to mucoid cells. From this it is concluded that specific release of secretory products from these cells can occur in the absence of hypothalmic control. A special form of collagenous fibre is produced in clump cultures. Monolayer cell cultures are derived either from isolated adenohypophysial cells or from secondarily aggregated clumps, but in either case the predominant cells are fibroblasts, which persist for over 50 days (as isolated cultures) and for over 90 days (as spreads from clumps). Rounded cells can be recognized as a separate type in isolated cell culture."} {"id": "PMID:179969", "title": "Ultrastructural features of human cerebral cortex.", "content": "Neuronal and glial elements have been examined in the temporal or frontal cortex of four brains with normal parenchyma. The identifying features recognized in animal brains have been found valid in human cortex for stellate and pyramidal neurons and their dendrites, spines, synapses, initial segments of axons, nodes of Ranvier and axon terminals; also for astrocytes, oligodendrocytes of various electron densities, pericytes, blood vessels and basement lamina, and for the relation of subarachnoid space to arterioles. However, most microglial cells have unexpectedly sparse and pale cytoplasm with few organelles, and the distribution of glial nuclear chromatin is not entirely in accordance with that described in animal brains. Fusiform neurons have been identified, and their cytoplasm resembles that of stellate cells. Peculiarities of human cortex include a nuclear inclusion that is present in stellate neurons only. Two neuronal cell-body profiles were myelinated, and a blood capillary was seen to penetrate a neuron. Somatic spines were found occasionally with or without synapses. Ribosomes can be present in axons, espicially at nodes of Ranvier, and a small portion of axon terminals contain a variety of dense bodies of which some are derived from mitochondria. Endoplasmic reticulum can occur in a compressed stack in neurons, and an unusual vesicular organelle has been seen in dendrites, axons and somata. Astrocytes as well as oligodendrocytes and occasional microglial cells act as satellites to neurons, and the exchange of a membrane-bound body between a neuron and asatellite glial cell is illustrated. Some dark pycnotic neurons were present, and it was remarkable that a closely apposed neuron could be entirely normal. These findings are compared with published descriptions of cortical ultrastructure in the brains of laboratory animals.", "contents": "Ultrastructural features of human cerebral cortex. Neuronal and glial elements have been examined in the temporal or frontal cortex of four brains with normal parenchyma. The identifying features recognized in animal brains have been found valid in human cortex for stellate and pyramidal neurons and their dendrites, spines, synapses, initial segments of axons, nodes of Ranvier and axon terminals; also for astrocytes, oligodendrocytes of various electron densities, pericytes, blood vessels and basement lamina, and for the relation of subarachnoid space to arterioles. However, most microglial cells have unexpectedly sparse and pale cytoplasm with few organelles, and the distribution of glial nuclear chromatin is not entirely in accordance with that described in animal brains. Fusiform neurons have been identified, and their cytoplasm resembles that of stellate cells. Peculiarities of human cortex include a nuclear inclusion that is present in stellate neurons only. Two neuronal cell-body profiles were myelinated, and a blood capillary was seen to penetrate a neuron. Somatic spines were found occasionally with or without synapses. Ribosomes can be present in axons, espicially at nodes of Ranvier, and a small portion of axon terminals contain a variety of dense bodies of which some are derived from mitochondria. Endoplasmic reticulum can occur in a compressed stack in neurons, and an unusual vesicular organelle has been seen in dendrites, axons and somata. Astrocytes as well as oligodendrocytes and occasional microglial cells act as satellites to neurons, and the exchange of a membrane-bound body between a neuron and asatellite glial cell is illustrated. Some dark pycnotic neurons were present, and it was remarkable that a closely apposed neuron could be entirely normal. These findings are compared with published descriptions of cortical ultrastructure in the brains of laboratory animals."} {"id": "PMID:179970", "title": "Synthesis of (beta-methyl-3H-)-benzylpenicillin and (beta-methyl-3H)-6-aminopenicillanic acid.", "content": "The synthesis of benzylpenicillin and 6-aminopenicillanic acid, labeled with tritium in the beta-methyl group, is described. Benzylpenicillin S-sulfoxide benzyl ester is refluxed in benzene and tritiated water and is successively debenzylated and deoxygenated to (beta-methyl-3H)-benzylpenicillin. Removal of the side chain with a bacterial acylase gives (beta-methyl-3H)-6-aminopenicillanic acid.", "contents": "Synthesis of (beta-methyl-3H-)-benzylpenicillin and (beta-methyl-3H)-6-aminopenicillanic acid. The synthesis of benzylpenicillin and 6-aminopenicillanic acid, labeled with tritium in the beta-methyl group, is described. Benzylpenicillin S-sulfoxide benzyl ester is refluxed in benzene and tritiated water and is successively debenzylated and deoxygenated to (beta-methyl-3H)-benzylpenicillin. Removal of the side chain with a bacterial acylase gives (beta-methyl-3H)-6-aminopenicillanic acid."} {"id": "PMID:179966", "title": "Comparison of herpes simplex virus isolates using a quantitative selection assay for transformation.", "content": "Transformation potential of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was quantitatively compared in a system selecting for biochemical transformants. The highest frequency of transformation was obtained with HSV-2 strain 333. The transformation rates for two strains of HSV-1 were lower and distinctly different from HSV-2 and from each other. The dose of inactivating ultraviolet light received by the virus and the multiplicity of infection proved to be critical components of the procedure. Clones of these biochemically transformed cells expressed HSV-specific antigens, altered cell morphology, and increased levels of thymidine kinase activity. Isolates of HSV-1 recovered from the same site 11 years apart yielded similar transforming frequencies. These results suggest that this assay should prove useful in further characterizing the biological properties of HSV.", "contents": "Comparison of herpes simplex virus isolates using a quantitative selection assay for transformation. Transformation potential of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was quantitatively compared in a system selecting for biochemical transformants. The highest frequency of transformation was obtained with HSV-2 strain 333. The transformation rates for two strains of HSV-1 were lower and distinctly different from HSV-2 and from each other. The dose of inactivating ultraviolet light received by the virus and the multiplicity of infection proved to be critical components of the procedure. Clones of these biochemically transformed cells expressed HSV-specific antigens, altered cell morphology, and increased levels of thymidine kinase activity. Isolates of HSV-1 recovered from the same site 11 years apart yielded similar transforming frequencies. These results suggest that this assay should prove useful in further characterizing the biological properties of HSV."} {"id": "PMID:179967", "title": "Particles morphologically resembling mouse hepatitis virus in nude mouse uterus.", "content": "Particles morphologically resembling mouse hepatitis virus were observed in uterine gland lumens and endometrial cells of 8 nude mice. Although 3 mice had been experimentally inoculated with baboon type C viral-infected materials, no ultrastructural evidence of oncornavirus-associated structures was observed.", "contents": "Particles morphologically resembling mouse hepatitis virus in nude mouse uterus. Particles morphologically resembling mouse hepatitis virus were observed in uterine gland lumens and endometrial cells of 8 nude mice. Although 3 mice had been experimentally inoculated with baboon type C viral-infected materials, no ultrastructural evidence of oncornavirus-associated structures was observed."} {"id": "PMID:179972", "title": "Respiratory load compensation in infants.", "content": "We have studied the respiratory compensation for elastic loads in 15 term and preterm infants. Elastic loads, approximately equal to the infant's effective elastance, were applied to the airway for five breaths while tidal volume and mask pressure were monitored. Motion of the rib cage and abdomen were monitored simultaneously with magnetometers. The studies were done both in active or REM sleep and in quiet or non-REM sleep. During quiet sleep the load immediately reduced the tidal volume by about 50% but a progressive increase in tidal volume occurred over the next four loaded breaths. During active sleep load compensation was disorganized with respect to both tidal volume and frequency, and compensation was significantly less. Active sleep was also characterized by marked rib cage distortion. We suggest that during active sleep there is tonic inhibition of the intercostal muscles, allowing the diaphragm to distort the rib cage. This distortion impairs load compensation by a direct mechanical effect and indirectly by initiating an intercostal-phrenic reflex.", "contents": "Respiratory load compensation in infants. We have studied the respiratory compensation for elastic loads in 15 term and preterm infants. Elastic loads, approximately equal to the infant's effective elastance, were applied to the airway for five breaths while tidal volume and mask pressure were monitored. Motion of the rib cage and abdomen were monitored simultaneously with magnetometers. The studies were done both in active or REM sleep and in quiet or non-REM sleep. During quiet sleep the load immediately reduced the tidal volume by about 50% but a progressive increase in tidal volume occurred over the next four loaded breaths. During active sleep load compensation was disorganized with respect to both tidal volume and frequency, and compensation was significantly less. Active sleep was also characterized by marked rib cage distortion. We suggest that during active sleep there is tonic inhibition of the intercostal muscles, allowing the diaphragm to distort the rib cage. This distortion impairs load compensation by a direct mechanical effect and indirectly by initiating an intercostal-phrenic reflex."} {"id": "PMID:179965", "title": "Presence of herpesvirus-associated antigens on the surfaces of transformed, tumor, and metastatic cells and enhanced antigenicity of transformed cells using 5-iodo-2'-deoxyuridine.", "content": "Using a direct immunofluorescence technique, herpes simplex virus type 1 (HSV-1)-transformed cells and cell lines subsequently derived from tumors and metastases were examined for the presence of HSV-1-associated surface antigens. Fluorescein-labeled immunoglobulins derived from antisera were used and included anti-HSV-1 (from hamsters), sera from tumor-bearing hamsters, and antibodies prepared in rabbits against cell material shed early into the medium after infection of rabbit kidney cells with HSV-1. All immunoglobulins showed the greatest reactivity with cell lines derived from tumors and metastatic lesions. There appeared to be little or no reactivity on the surfaces of the transformed cells. Transformed cells treated with 5-iodo-2'-deoxyuridine for 48 h, however, showed an enhanced reactivity which approached that seen with the tumor-derived cell lines.", "contents": "Presence of herpesvirus-associated antigens on the surfaces of transformed, tumor, and metastatic cells and enhanced antigenicity of transformed cells using 5-iodo-2'-deoxyuridine. Using a direct immunofluorescence technique, herpes simplex virus type 1 (HSV-1)-transformed cells and cell lines subsequently derived from tumors and metastases were examined for the presence of HSV-1-associated surface antigens. Fluorescein-labeled immunoglobulins derived from antisera were used and included anti-HSV-1 (from hamsters), sera from tumor-bearing hamsters, and antibodies prepared in rabbits against cell material shed early into the medium after infection of rabbit kidney cells with HSV-1. All immunoglobulins showed the greatest reactivity with cell lines derived from tumors and metastatic lesions. There appeared to be little or no reactivity on the surfaces of the transformed cells. Transformed cells treated with 5-iodo-2'-deoxyuridine for 48 h, however, showed an enhanced reactivity which approached that seen with the tumor-derived cell lines."} {"id": "PMID:179973", "title": "Effects of crp mutations on adenosine 3',5'-monophosphate metabolism in Salmonella typhimurium.", "content": "Wild-type Salmonella typhimurium could not grow with exogenous cyclic adenosine 3',5'-monophosphate (AMP) as the sole source of phosphate, but mutants capable of cyclic AMP utilization could be isolated provided the parental strain contained a functional cyclic AMP phosphodiesterase.All cyclic AMP-utilizing mutants had the growth and fermentation properties of cyclic AMP receptor protein (crp) mutants, and some lacked cyclic AMP binding activity in vitro. The genetic defect in each such mutant was due to a single point mutation, which was co-transducible with cysG. crp mutants isolated by alternative procedures also exhibited the capacity to utilize cyclic AMP. crp mutants synthesized cyclic AMP at increased rates and contained enhanced cellular cyclic AMP levels relative to the parental strains, regardless of whether or not cyclic AMP phosphodiesterase was active. Moreover, adenylate cyclase activity in vivo was less sensitive to regulation by glucose, possibly because the enzyme II complexes of the phosphotransferase system, responsible for glucose transport and phosphorylation, could not be induced to maximal levels. This possibility was strengthened by the observation that enzyme II activity (measured both in vitro by sugar phosphorylation and in vivo by sugar transport and chemotaxis) was inducible in the parental strain but not in crp mutants. The results suggest that the cyclic AMP receptor protein regulates cyclic AMP metabolism as well as catabolic enzyme synthesis.", "contents": "Effects of crp mutations on adenosine 3',5'-monophosphate metabolism in Salmonella typhimurium. Wild-type Salmonella typhimurium could not grow with exogenous cyclic adenosine 3',5'-monophosphate (AMP) as the sole source of phosphate, but mutants capable of cyclic AMP utilization could be isolated provided the parental strain contained a functional cyclic AMP phosphodiesterase.All cyclic AMP-utilizing mutants had the growth and fermentation properties of cyclic AMP receptor protein (crp) mutants, and some lacked cyclic AMP binding activity in vitro. The genetic defect in each such mutant was due to a single point mutation, which was co-transducible with cysG. crp mutants isolated by alternative procedures also exhibited the capacity to utilize cyclic AMP. crp mutants synthesized cyclic AMP at increased rates and contained enhanced cellular cyclic AMP levels relative to the parental strains, regardless of whether or not cyclic AMP phosphodiesterase was active. Moreover, adenylate cyclase activity in vivo was less sensitive to regulation by glucose, possibly because the enzyme II complexes of the phosphotransferase system, responsible for glucose transport and phosphorylation, could not be induced to maximal levels. This possibility was strengthened by the observation that enzyme II activity (measured both in vitro by sugar phosphorylation and in vivo by sugar transport and chemotaxis) was inducible in the parental strain but not in crp mutants. The results suggest that the cyclic AMP receptor protein regulates cyclic AMP metabolism as well as catabolic enzyme synthesis."} {"id": "PMID:179974", "title": "Regulation of tyramine oxidase synthesis in Klebsiella aerogenes.", "content": "Tyramine oxidase in Klebsiella aerogenes is highly specific for tyramine, dopamine, octopamine, and norepinephrine, and its synthesis is induced specifically by these compounds. The enzyme is present in a membrane-bound form. The Km value for tyramine is 9 X 10(-4) M. Tyramine oxidase synthesis was subjected to catabolite repression by glucose in the presence of ammonium salts. Addition of cyclic adenosine 3',5'-monophosphate (cAMP) overcame the catabolite repression. A mutant strain, K711, which can produce a high level of beta-galactosidase in the presence of glucose and ammonium chloride, can also synthesize tyramine oxidase and histidase in the presence of inducer in glucose ammonium medium. Catabolite repression of tyramine oxidase synthesis was relieved when the cells were grown under conditions of nitrogen limitation, whereas beta-galactosidase was strongly repressed under these conditions. A cAMP-requiring mutant, MK54, synthesized tyramine oxidase rapidly when tyramine was used as the sole source of nitrogen in the absence of cAMP. However, a glutamine synthetase-constitutive mutant, MK94, failed to synthesize tyramine oxidase in the presence of glucose and ammonium chloride, although it synthesized histidase rapidly under these conditions. These results suggest that catabolite repression of tyramine oxidase synthesis in K. aerogenes is regulated by the intracellular level of cAMP and an unknown cytoplasmic factor that acts independently of cAMP and is formed under conditions of nitrogen limitation.", "contents": "Regulation of tyramine oxidase synthesis in Klebsiella aerogenes. Tyramine oxidase in Klebsiella aerogenes is highly specific for tyramine, dopamine, octopamine, and norepinephrine, and its synthesis is induced specifically by these compounds. The enzyme is present in a membrane-bound form. The Km value for tyramine is 9 X 10(-4) M. Tyramine oxidase synthesis was subjected to catabolite repression by glucose in the presence of ammonium salts. Addition of cyclic adenosine 3',5'-monophosphate (cAMP) overcame the catabolite repression. A mutant strain, K711, which can produce a high level of beta-galactosidase in the presence of glucose and ammonium chloride, can also synthesize tyramine oxidase and histidase in the presence of inducer in glucose ammonium medium. Catabolite repression of tyramine oxidase synthesis was relieved when the cells were grown under conditions of nitrogen limitation, whereas beta-galactosidase was strongly repressed under these conditions. A cAMP-requiring mutant, MK54, synthesized tyramine oxidase rapidly when tyramine was used as the sole source of nitrogen in the absence of cAMP. However, a glutamine synthetase-constitutive mutant, MK94, failed to synthesize tyramine oxidase in the presence of glucose and ammonium chloride, although it synthesized histidase rapidly under these conditions. These results suggest that catabolite repression of tyramine oxidase synthesis in K. aerogenes is regulated by the intracellular level of cAMP and an unknown cytoplasmic factor that acts independently of cAMP and is formed under conditions of nitrogen limitation."} {"id": "PMID:179975", "title": "Repression of Escherichia coli carbamoylphosphate synthase: relationships with enzyme synthesis in the arginine and pyrimidine pathways.", "content": "Cumulative repression of Escherichia coli carbamoylphosphate synthase (CPSase; EC 2.7.2.9) by arginine and pyrimidine was analyzed in relation to control enzyme synthesis in the arginine and pyrimidine pathways. The expression of carA and carB, the adjacent genes that specify the two subunits of the enzyme, was estimated by means of an in vitro complementation assay. The synthesis of each gene product was found to be under repression control. Coordinate expression of the two genes was observed under most conditions investigated. They might thus form an operon. The preparation of strains blocked in the degradation of cytidine and harboring leaky mutations affecting several steps of pyrimidine nucleotide synthesis made it possible to distinguish between the effects of cytidine and uridine compounds in the repression of the pyrimidine pathway enzymes. The data obtained suggest that derivatives of both cytidine and uridine participate in the repression of CPSase. In addition, repression of CPSase by arginine did not appear to occur unless pyrimidines were present at a significant intracellular concentration. This observation, together with our previous report that argR mutations impair the cumulative repression of CPSase, suggests that this control is mediated through the concerted effects of regulatory elements specific for the arginine and pyrimidine pathways.", "contents": "Repression of Escherichia coli carbamoylphosphate synthase: relationships with enzyme synthesis in the arginine and pyrimidine pathways. Cumulative repression of Escherichia coli carbamoylphosphate synthase (CPSase; EC 2.7.2.9) by arginine and pyrimidine was analyzed in relation to control enzyme synthesis in the arginine and pyrimidine pathways. The expression of carA and carB, the adjacent genes that specify the two subunits of the enzyme, was estimated by means of an in vitro complementation assay. The synthesis of each gene product was found to be under repression control. Coordinate expression of the two genes was observed under most conditions investigated. They might thus form an operon. The preparation of strains blocked in the degradation of cytidine and harboring leaky mutations affecting several steps of pyrimidine nucleotide synthesis made it possible to distinguish between the effects of cytidine and uridine compounds in the repression of the pyrimidine pathway enzymes. The data obtained suggest that derivatives of both cytidine and uridine participate in the repression of CPSase. In addition, repression of CPSase by arginine did not appear to occur unless pyrimidines were present at a significant intracellular concentration. This observation, together with our previous report that argR mutations impair the cumulative repression of CPSase, suggests that this control is mediated through the concerted effects of regulatory elements specific for the arginine and pyrimidine pathways."} {"id": "PMID:179976", "title": "Isolation and heteroduplex mapping of a lambda transducing bacteriophage carrying the structural genes for carbamoylphosphate synthase: regulation of enzyme synthesis in Escherichia coli K-12 lysogens.", "content": "A N-lambda bacteriophage transducing the structural genes for Escherichia coli K-12 carbamoylphosphate synthase (glutamine) (CPSase; EC 2.7.2.9) has been isolated and analyzed both genetically and physically. The whole int-N region is substituted for a short chromosomal segment corresponding almost exactly to the car locus. The study of CPSase, ornithine carbamoyltransferase, and aspartate carbamoyltransferase regulation in carriers of lambdadcar confirms the previously reported participation of the argR gene product in the control of CPSase synthesis and points to the existence of a regulatory molecule involved in the control of both CPSase and aspartate carbamoyltransferase synthesis. The general usefulness of using N- lambda transducing bacteriophages for the recovery of large amounts of gene products is discussed.", "contents": "Isolation and heteroduplex mapping of a lambda transducing bacteriophage carrying the structural genes for carbamoylphosphate synthase: regulation of enzyme synthesis in Escherichia coli K-12 lysogens. A N-lambda bacteriophage transducing the structural genes for Escherichia coli K-12 carbamoylphosphate synthase (glutamine) (CPSase; EC 2.7.2.9) has been isolated and analyzed both genetically and physically. The whole int-N region is substituted for a short chromosomal segment corresponding almost exactly to the car locus. The study of CPSase, ornithine carbamoyltransferase, and aspartate carbamoyltransferase regulation in carriers of lambdadcar confirms the previously reported participation of the argR gene product in the control of CPSase synthesis and points to the existence of a regulatory molecule involved in the control of both CPSase and aspartate carbamoyltransferase synthesis. The general usefulness of using N- lambda transducing bacteriophages for the recovery of large amounts of gene products is discussed."} {"id": "PMID:179977", "title": "Peptidoglycan biosynthesis in Micrococcus luteus (sodonensis): transglycosidase and phosphodiesterase activities in membrane preparations.", "content": "Two enzyme activities involved in the biosynthesis of peptidoglycan in Micrococcus luteus (sodonensis), a transglycosidase and a phosphodiesterase, have been demonstrated in isolated membrane preparations. The transglycosidase activity promotes the in vitro synthesis of an uncross-bridged peptidoglycan that is completely susceptible to lysozyme. This in vitro-synthesized peptidoglycan consists of 76% \"soluble\" and 24% \"insoluble\" material. The soluble peptidoglycan is primarily a single low-molecular-weight species of approximately 20 disaccharide peptide units. \"Insoluble\" peptidoglycan, which likely represents newly synthesized material incorporated into an existing cell wall, was solubilized by butanol extraction, and the two were compared. The phosphodiesterase activity demonstrated in this system cleaves uridine diphosphate-N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysyl-D-alanyl-D-alanine to yield N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysyl-D-alanyl-D-alanine plus uridine 5'-monophosphate plus inorganic phosphate. This phosphodiesterase activity, not detected under normal transglycosidase assay conditions, is a recycling mechanism and acts indirectly through formation and subsequent cleavage of a lipid-linked intermediate.", "contents": "Peptidoglycan biosynthesis in Micrococcus luteus (sodonensis): transglycosidase and phosphodiesterase activities in membrane preparations. Two enzyme activities involved in the biosynthesis of peptidoglycan in Micrococcus luteus (sodonensis), a transglycosidase and a phosphodiesterase, have been demonstrated in isolated membrane preparations. The transglycosidase activity promotes the in vitro synthesis of an uncross-bridged peptidoglycan that is completely susceptible to lysozyme. This in vitro-synthesized peptidoglycan consists of 76% \"soluble\" and 24% \"insoluble\" material. The soluble peptidoglycan is primarily a single low-molecular-weight species of approximately 20 disaccharide peptide units. \"Insoluble\" peptidoglycan, which likely represents newly synthesized material incorporated into an existing cell wall, was solubilized by butanol extraction, and the two were compared. The phosphodiesterase activity demonstrated in this system cleaves uridine diphosphate-N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysyl-D-alanyl-D-alanine to yield N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysyl-D-alanyl-D-alanine plus uridine 5'-monophosphate plus inorganic phosphate. This phosphodiesterase activity, not detected under normal transglycosidase assay conditions, is a recycling mechanism and acts indirectly through formation and subsequent cleavage of a lipid-linked intermediate."} {"id": "PMID:179978", "title": "Characterization of intracytoplasmic hydrocarbon inclusions from the hydrocarbon-oxidizing Acinetobacter species HO1-N.", "content": "The ultrastructure of Acinetobacter sp. strain HO1-N grown on hydrocarbon and nonhydrocarbon substrates was compared using thin sections and freeze-etching. Hydrocarbon-grown cells were characterized by the presence of intracytoplasmic membrane-bound hexadecane inclusions. This membrane did not exhibit a typical unit membrane structure but appeared as a monolayer. The freeze-etch technique revealed the internal structure of the hexadecane inclusions and provided evidence for the presence of a smooth-surfaced limiting membrane. Freeze-etching also revealed intracytoplasmic membranes in the hexadecane-grown cells. These ultrastructural modifications were not present in nonhydrocarbon-grown cells. The hexadecane inclusions were isolated from Acinetobacter. Negative-staining of the inclusions revealed electron-transparent vesicles approximating the size of the inclusions seen in whole cells. Freeze-etching of the purified inclusions revealed membrane-bound vesicles. The purified inclusions exhibited a relatively high value of lipid phosphorus to protein. The lipid composition and the electrophoretic banding pattern of the inclusions on sodium dodecyl sulfate-polyacrylamide gels were determined and compared with other membrane fractions (outer membrane and cytoplasmic membrane) previously isolated from this organism.", "contents": "Characterization of intracytoplasmic hydrocarbon inclusions from the hydrocarbon-oxidizing Acinetobacter species HO1-N. The ultrastructure of Acinetobacter sp. strain HO1-N grown on hydrocarbon and nonhydrocarbon substrates was compared using thin sections and freeze-etching. Hydrocarbon-grown cells were characterized by the presence of intracytoplasmic membrane-bound hexadecane inclusions. This membrane did not exhibit a typical unit membrane structure but appeared as a monolayer. The freeze-etch technique revealed the internal structure of the hexadecane inclusions and provided evidence for the presence of a smooth-surfaced limiting membrane. Freeze-etching also revealed intracytoplasmic membranes in the hexadecane-grown cells. These ultrastructural modifications were not present in nonhydrocarbon-grown cells. The hexadecane inclusions were isolated from Acinetobacter. Negative-staining of the inclusions revealed electron-transparent vesicles approximating the size of the inclusions seen in whole cells. Freeze-etching of the purified inclusions revealed membrane-bound vesicles. The purified inclusions exhibited a relatively high value of lipid phosphorus to protein. The lipid composition and the electrophoretic banding pattern of the inclusions on sodium dodecyl sulfate-polyacrylamide gels were determined and compared with other membrane fractions (outer membrane and cytoplasmic membrane) previously isolated from this organism."} {"id": "PMID:179979", "title": "D-Ribulose-1,5-bisphosphate carboxylase and polyhedral inclusion bodies in Thiobacillus intermedius.", "content": "The growth-related parameters of Thiobacillus intermedius, cultured in glutamate-CO2-S2O32- medium, have been determined. After centrifugation at 48,000 X g for 1 h, 24% of the D-ribulose-1,5-bisphosphate carboxylase (RuBPCase) activity of the disrupted-cell suspensions obtained from CO2-S2O32--and glutamate-CO2-S2O3(3)- grown cells could be sedimented, and the specific activities of this enzyme in the supernatant fractions were almost equivalent. The enzyme was stable in T. intermedius starved of thiosulfate in the presence and absence of glutamate, but a progressive decrease was evident in several growth cycles, each cycle supported by resupplementation of cells with thiosulfate. Polyhedral inclusion bodies were present in CO2-S2O3(2)- and glutamate-CO2S2O3(2)- grown cells. The number of polyhedral bodies per cell increased during mixotrophic growth approximately in proportion to the observed increase in the specific activity of RuBPCase. RuBPCase could not be detected in T. intermedius grown heterotrophically on yeast extract, nor could polyhedral bodies be found.", "contents": "D-Ribulose-1,5-bisphosphate carboxylase and polyhedral inclusion bodies in Thiobacillus intermedius. The growth-related parameters of Thiobacillus intermedius, cultured in glutamate-CO2-S2O32- medium, have been determined. After centrifugation at 48,000 X g for 1 h, 24% of the D-ribulose-1,5-bisphosphate carboxylase (RuBPCase) activity of the disrupted-cell suspensions obtained from CO2-S2O32--and glutamate-CO2-S2O3(3)- grown cells could be sedimented, and the specific activities of this enzyme in the supernatant fractions were almost equivalent. The enzyme was stable in T. intermedius starved of thiosulfate in the presence and absence of glutamate, but a progressive decrease was evident in several growth cycles, each cycle supported by resupplementation of cells with thiosulfate. Polyhedral inclusion bodies were present in CO2-S2O3(2)- and glutamate-CO2S2O3(2)- grown cells. The number of polyhedral bodies per cell increased during mixotrophic growth approximately in proportion to the observed increase in the specific activity of RuBPCase. RuBPCase could not be detected in T. intermedius grown heterotrophically on yeast extract, nor could polyhedral bodies be found."} {"id": "PMID:179980", "title": "Control of the synthesis of alkaline phosphatase and the phosphate-binding protein in Escherichia coli.", "content": "Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunological techniques, we have compared the synthesis of the phoA protein (alkaline phosphatase) and the phoS protein (phosphate-binding protein) in response to the level of phosphate in the medium in different genetic backgrounds containing the known alkaline phosphatase control mutations. Both proteins are produced in excess phosphate media in a phoR1a- strain, whereas neither protein is produced in a phoB- strain even under derepression conditions. In four different phoR1c- strains, however, the phoA product cannot be detected in extracts of cells obtained from any growth condition, whereas the phoS product is produced in both excess and limiting phosphate media. It is not yet known if phoR1c- mutants are a special class of mutations within the phoB gene or whether they occur in a separate cistron involved in alkaline phosphatase regulation. From these results we conclude that the expression of the phoA gene is not always co-regulated with expression of the phoS gene product. We have determined that the phoS protein is a component of periplasmic protein band P4 described by Morris et al. (1974). The phoS product lacks sulfur-containing amino acids and is extractable by treatment with polymyxin sulfate. The other component of band P4 contains methionine and/or cysteine and is not extracted by polymyxin sulfate treatment. Like the phoS and phoA proteins, its synthesis is sensitive to the concentration of phosphate in the growth medium. In addition, the existence of a new class of periplasmic proteins synthesized at maximum rate in high phosphate media is demonstrated.", "contents": "Control of the synthesis of alkaline phosphatase and the phosphate-binding protein in Escherichia coli. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunological techniques, we have compared the synthesis of the phoA protein (alkaline phosphatase) and the phoS protein (phosphate-binding protein) in response to the level of phosphate in the medium in different genetic backgrounds containing the known alkaline phosphatase control mutations. Both proteins are produced in excess phosphate media in a phoR1a- strain, whereas neither protein is produced in a phoB- strain even under derepression conditions. In four different phoR1c- strains, however, the phoA product cannot be detected in extracts of cells obtained from any growth condition, whereas the phoS product is produced in both excess and limiting phosphate media. It is not yet known if phoR1c- mutants are a special class of mutations within the phoB gene or whether they occur in a separate cistron involved in alkaline phosphatase regulation. From these results we conclude that the expression of the phoA gene is not always co-regulated with expression of the phoS gene product. We have determined that the phoS protein is a component of periplasmic protein band P4 described by Morris et al. (1974). The phoS product lacks sulfur-containing amino acids and is extractable by treatment with polymyxin sulfate. The other component of band P4 contains methionine and/or cysteine and is not extracted by polymyxin sulfate treatment. Like the phoS and phoA proteins, its synthesis is sensitive to the concentration of phosphate in the growth medium. In addition, the existence of a new class of periplasmic proteins synthesized at maximum rate in high phosphate media is demonstrated."} {"id": "PMID:179981", "title": "Association of messenger ribonucleic acid with 70S monosomes from down-shifted Escherichia coli.", "content": "The complexed 70S ribosomes (monosomes) that accumulate in Escherichia coli after an energy source shift-down were examined in an electron microscope. In all cases, the ribosomes lie at or near one end of a ribonucleic acid (RNA) strand. This messenger RNA (mRNA) has a mean length of 168 nm and a length-average length of 200 nm, sufficient to code for polypeptides of a weight-average molecular weight of 20,000. The length distribution indicates that these strands are a reasonable representation of the population of monocistronic mRNA's of E. coli. The mRNA strands disappear entirely upon digestion with pancreatic ribonuclease, phosphodiesterase I, or polynucleotide phosphorylase. The susceptibility to digestion by 3'-exonucleases indicate that the ribosomes lie at the 5' end of the mRNA strands. These results are consistent with the hypothesis that down-shifted cells have a translational defect at a point subsequent to the binding of ribosomes to mRNA but prior to the formation of the first peptide bond, such that ribosomes remain bound at or near their points of initial attachment to mRNA.", "contents": "Association of messenger ribonucleic acid with 70S monosomes from down-shifted Escherichia coli. The complexed 70S ribosomes (monosomes) that accumulate in Escherichia coli after an energy source shift-down were examined in an electron microscope. In all cases, the ribosomes lie at or near one end of a ribonucleic acid (RNA) strand. This messenger RNA (mRNA) has a mean length of 168 nm and a length-average length of 200 nm, sufficient to code for polypeptides of a weight-average molecular weight of 20,000. The length distribution indicates that these strands are a reasonable representation of the population of monocistronic mRNA's of E. coli. The mRNA strands disappear entirely upon digestion with pancreatic ribonuclease, phosphodiesterase I, or polynucleotide phosphorylase. The susceptibility to digestion by 3'-exonucleases indicate that the ribosomes lie at the 5' end of the mRNA strands. These results are consistent with the hypothesis that down-shifted cells have a translational defect at a point subsequent to the binding of ribosomes to mRNA but prior to the formation of the first peptide bond, such that ribosomes remain bound at or near their points of initial attachment to mRNA."} {"id": "PMID:179982", "title": "Natural and altered induction of the L-fucose catabolic enzymes in Klebsiella aerogenes.", "content": "Mutants of Klebsiella aerogenes W70 were isolated that had gained the ability to utilize the uncommon pentose D-arabinose as their sole source of carbon and energy. In contrast to the D-arabinose-negative, parent strain, these mutants were found to be either constitutive for certain enzymes of the L-fucose catabolic pathway or inducible for such enzymes when incubated in the presence of D-arabinose. The mutants used L-fucose isomerase to convert D-arabinose to D-ribulose, which is an intermediate and inducer of the ribitol catabolic pathway. The D-ribulokinase of the ribitol pathway was then induced. This enzyme catalyzed the phosphorylation of D-ribulose at the 5-carbon position. Mutants that were negative for D-ribulokinase could still dissimilate D-arabinose slowly by using all three enzymes, the isomerase, kinase, and aldolase, of the L-fucose pathway. Using condition negative mutants, we were able to demonstrate that the natural induction of the L-fucose pathway enzymes by L-fucose required the activity of a functional L-fucose isomerase and a functional L-fuculokinase but not an L-fuculose-1-phosphate aldolase. A metabolic intermediate, L-fuculose-1-phosphate, was thereby shown to be a probable inducer of at least the isomerase and kinase of the L-fucose catabolic pathway. Similar experiments, with D-arabinose-positive mutants, which were induced for the L-fucose pathway enzymes upon incubation with D-arabinose, revealed that the activities of the L-fucose isomerase and the L-fuculokinase were also required for the induction of the L-fucose enzymes. These D-arabinose-positive mutants apparently produced an altered regulatory protein that accepted both L-fuculose-1-phosphate and D-ribulose-1-phosphate as inducers. Examination of constitutive mutants revealed that L-fucose isomerase and L-fuculokinase were both synthesized constitutively, with the aldolase apparently under separate control.", "contents": "Natural and altered induction of the L-fucose catabolic enzymes in Klebsiella aerogenes. Mutants of Klebsiella aerogenes W70 were isolated that had gained the ability to utilize the uncommon pentose D-arabinose as their sole source of carbon and energy. In contrast to the D-arabinose-negative, parent strain, these mutants were found to be either constitutive for certain enzymes of the L-fucose catabolic pathway or inducible for such enzymes when incubated in the presence of D-arabinose. The mutants used L-fucose isomerase to convert D-arabinose to D-ribulose, which is an intermediate and inducer of the ribitol catabolic pathway. The D-ribulokinase of the ribitol pathway was then induced. This enzyme catalyzed the phosphorylation of D-ribulose at the 5-carbon position. Mutants that were negative for D-ribulokinase could still dissimilate D-arabinose slowly by using all three enzymes, the isomerase, kinase, and aldolase, of the L-fucose pathway. Using condition negative mutants, we were able to demonstrate that the natural induction of the L-fucose pathway enzymes by L-fucose required the activity of a functional L-fucose isomerase and a functional L-fuculokinase but not an L-fuculose-1-phosphate aldolase. A metabolic intermediate, L-fuculose-1-phosphate, was thereby shown to be a probable inducer of at least the isomerase and kinase of the L-fucose catabolic pathway. Similar experiments, with D-arabinose-positive mutants, which were induced for the L-fucose pathway enzymes upon incubation with D-arabinose, revealed that the activities of the L-fucose isomerase and the L-fuculokinase were also required for the induction of the L-fucose enzymes. These D-arabinose-positive mutants apparently produced an altered regulatory protein that accepted both L-fuculose-1-phosphate and D-ribulose-1-phosphate as inducers. Examination of constitutive mutants revealed that L-fucose isomerase and L-fuculokinase were both synthesized constitutively, with the aldolase apparently under separate control."} {"id": "PMID:179983", "title": "Achromobacter cycloclastes nitrite reductase. The function of copper, amino acid composition, and ESR spectra.", "content": "1. Dialysis against cyanide at pH 7 of Achromobacter cycloclastes nitrite reductase [EC 1.7.99.3] of a dissimilatory type led to the removal of about 50% of the copper from the enzyme molecule, with a concomitant decrease of the enzymatic activities. It was inferred that enzyme-bound copper atoms play an essential role in the catalytic activities of the enzyme. 2. The amino acid composition of the enzyme was determined after acid hydrolysis. 3. ESR spectra of the frozen solution and lyophilized powder of the nitrite reductase predominantly showed the presence of two kinds of copper: Type 1 Cu2+, which had narrow and sharp hyperfine splitting, and Type 2 Cu2+, which had broader hyperfine splitting. The bond between the oxidized enzyme and nitrite seems to be ionic.", "contents": "Achromobacter cycloclastes nitrite reductase. The function of copper, amino acid composition, and ESR spectra. 1. Dialysis against cyanide at pH 7 of Achromobacter cycloclastes nitrite reductase [EC 1.7.99.3] of a dissimilatory type led to the removal of about 50% of the copper from the enzyme molecule, with a concomitant decrease of the enzymatic activities. It was inferred that enzyme-bound copper atoms play an essential role in the catalytic activities of the enzyme. 2. The amino acid composition of the enzyme was determined after acid hydrolysis. 3. ESR spectra of the frozen solution and lyophilized powder of the nitrite reductase predominantly showed the presence of two kinds of copper: Type 1 Cu2+, which had narrow and sharp hyperfine splitting, and Type 2 Cu2+, which had broader hyperfine splitting. The bond between the oxidized enzyme and nitrite seems to be ionic."} {"id": "PMID:179984", "title": "A new form of high molecular weight DNA polymerase in the nuclei of rat ascites hepatoma cells.", "content": "A new form of high molecular weight DNA polymerase [EC 2.7.7.7] (polymerase N) was isolated from the nuclei of rat ascites hepatoma cells. Polymerase C, which was isolated previously from whole cell extract, was also isolated from the nuclei (Tsuruo, T. and Ukita, T. (1974) Biochim. Biophys. Acta 353, 146-159). Polymerase N was not found in the cytoplasmic fraction of the cell, while polymerase C existed in both the nucleus and cytoplasm. The molecular weight of polymerase N (8.7 S) was larger than that of polymerase C (7.4 S). On freezing and thawing, polymerase N was converted to polymerase C. In the nucleus the amount of polymerase N was larger than that of polymerase C. These data suggest that polymerase N, which was specifically present in the nucleus, was a complex form of polymerase C. In in vitro assay, polymerase N showed properties similar to those of polymerase C. Oligoribonucleotide was an effective initiator for the polymerization reaction by polymerase N. The DNA synthesis on single stranded fd phage DNA was greatly stimulated by the concomitant synthesis of RNA.", "contents": "A new form of high molecular weight DNA polymerase in the nuclei of rat ascites hepatoma cells. A new form of high molecular weight DNA polymerase [EC 2.7.7.7] (polymerase N) was isolated from the nuclei of rat ascites hepatoma cells. Polymerase C, which was isolated previously from whole cell extract, was also isolated from the nuclei (Tsuruo, T. and Ukita, T. (1974) Biochim. Biophys. Acta 353, 146-159). Polymerase N was not found in the cytoplasmic fraction of the cell, while polymerase C existed in both the nucleus and cytoplasm. The molecular weight of polymerase N (8.7 S) was larger than that of polymerase C (7.4 S). On freezing and thawing, polymerase N was converted to polymerase C. In the nucleus the amount of polymerase N was larger than that of polymerase C. These data suggest that polymerase N, which was specifically present in the nucleus, was a complex form of polymerase C. In in vitro assay, polymerase N showed properties similar to those of polymerase C. Oligoribonucleotide was an effective initiator for the polymerization reaction by polymerase N. The DNA synthesis on single stranded fd phage DNA was greatly stimulated by the concomitant synthesis of RNA."} {"id": "PMID:179988", "title": "A new kinetic property characteristic of the actomyosin-nucleoside-triphosphatase.", "content": "The nucleoside triphosphatase [EC 3.6.1.15] activity of actomysin and that of myosin are measured by varying the concentration of nucleoside triphosphate and that of CaCl2 or MgGl2. The results thus obtained are examined by asking a question of which is responsbile for the activity, the true substrate and the active enzyme in terms of the reaction scheme shown in p. 719. The answers found for the above question are summarized in Table I (see p. 720). It is emphasized that the summmary (Table I) corresponds very well to the fact that myosin alone does not superprecipitate in the presence of either calcium or magnesium ions, whereas actomyosin does superprecipitate in the presence of magnesium ions and not in the presence of calcium ions. Obviously, the true substrate type of reaction scheme represents a kinetic property characteristic of the superprecipitation-coupled nucleoside-triphosphatase. It is also noted of the summary (Table I) that actin is capable of not only activating Mg-nucleoside-triphosphatase but also switiching the reaction scheme from the active enzyme type to the true substrate type. It is known that trinitrophenylation of myosin results in activation of the Mg-ATPase activity of myosin. However, it is now found that trinitrophenylation is not capable of switiching the reaction scheme, that is to say that the Mg-ATPase reaction of trinitrophenyl-myosin stays with the active enzyme type of reaction scheme and that of acto-trinitrophenyl-myosin with the true substrate type of reaction scheme. Effect of actin on the function of myosin seems, therefore, very unique.", "contents": "A new kinetic property characteristic of the actomyosin-nucleoside-triphosphatase. The nucleoside triphosphatase [EC 3.6.1.15] activity of actomysin and that of myosin are measured by varying the concentration of nucleoside triphosphate and that of CaCl2 or MgGl2. The results thus obtained are examined by asking a question of which is responsbile for the activity, the true substrate and the active enzyme in terms of the reaction scheme shown in p. 719. The answers found for the above question are summarized in Table I (see p. 720). It is emphasized that the summmary (Table I) corresponds very well to the fact that myosin alone does not superprecipitate in the presence of either calcium or magnesium ions, whereas actomyosin does superprecipitate in the presence of magnesium ions and not in the presence of calcium ions. Obviously, the true substrate type of reaction scheme represents a kinetic property characteristic of the superprecipitation-coupled nucleoside-triphosphatase. It is also noted of the summary (Table I) that actin is capable of not only activating Mg-nucleoside-triphosphatase but also switiching the reaction scheme from the active enzyme type to the true substrate type. It is known that trinitrophenylation of myosin results in activation of the Mg-ATPase activity of myosin. However, it is now found that trinitrophenylation is not capable of switiching the reaction scheme, that is to say that the Mg-ATPase reaction of trinitrophenyl-myosin stays with the active enzyme type of reaction scheme and that of acto-trinitrophenyl-myosin with the true substrate type of reaction scheme. Effect of actin on the function of myosin seems, therefore, very unique."} {"id": "PMID:179989", "title": "Isolation and characterization of the plasma membranes from rat ascites hepatomas and from normal rat livers, including newborn, regenerating, and adult livers.", "content": "Plasma membranes (PM) were isolated from island-forming types of rat ascites hepatoma (AH 130, AH 602, and AH 7974) and from their free-cell sublines (AH 130FN and AH 7974F), and were characterized in terms of electron-microscopic morphology, marker enzyme activities, and lipid contents. The results were compared with those of the PM isolated in a similar way from newborn, regenerating, and adult livers. The marker enzyme activities, such as Na+, K+-insensitive Mg2+-ATPase [EC 3.6.1.3] (Mg2+-ATPase) and 5'-nucleotidase [EC 3.1.3.5], as well as the phospholipid composition of the PM isolated from hepatomas by Wallach's nitrogen gas cavitation method were similar to those obtained with the PM isolated by a modification of Emmelot's method, although the former method gave a much lower yield in terms of protein than the latter. Based on the modified Emmelot method, sufficiently pure PM preparations could be obtained from the hepatomas in the form of large membrane sheets without any contamination by other identifiable components, as determined with an electron microscope, and with high specific activities of the marker enzymes, such as Na+, K+-sensitive ATPase [EC 3.6.1.3] (Na+, K+ -ATPase), Mg2+ -ATPase, and 5'-nucleotidase. As for the characteristics of the hepatoma PM, lower specific activity of 5'-nucleotidase and higher fatty aldehyde molar percentages in total phospholipids were noted in all the PM from the hepatomas in comparison with normal liver PM of various origins. The PM from the hepatomas showed an increased amount of cholesterol (mumole per mg protein), whereas actively growing newborn and regenerating livers gave rather lower amounts in comparison with that of normal adult liver.", "contents": "Isolation and characterization of the plasma membranes from rat ascites hepatomas and from normal rat livers, including newborn, regenerating, and adult livers. Plasma membranes (PM) were isolated from island-forming types of rat ascites hepatoma (AH 130, AH 602, and AH 7974) and from their free-cell sublines (AH 130FN and AH 7974F), and were characterized in terms of electron-microscopic morphology, marker enzyme activities, and lipid contents. The results were compared with those of the PM isolated in a similar way from newborn, regenerating, and adult livers. The marker enzyme activities, such as Na+, K+-insensitive Mg2+-ATPase [EC 3.6.1.3] (Mg2+-ATPase) and 5'-nucleotidase [EC 3.1.3.5], as well as the phospholipid composition of the PM isolated from hepatomas by Wallach's nitrogen gas cavitation method were similar to those obtained with the PM isolated by a modification of Emmelot's method, although the former method gave a much lower yield in terms of protein than the latter. Based on the modified Emmelot method, sufficiently pure PM preparations could be obtained from the hepatomas in the form of large membrane sheets without any contamination by other identifiable components, as determined with an electron microscope, and with high specific activities of the marker enzymes, such as Na+, K+-sensitive ATPase [EC 3.6.1.3] (Na+, K+ -ATPase), Mg2+ -ATPase, and 5'-nucleotidase. As for the characteristics of the hepatoma PM, lower specific activity of 5'-nucleotidase and higher fatty aldehyde molar percentages in total phospholipids were noted in all the PM from the hepatomas in comparison with normal liver PM of various origins. The PM from the hepatomas showed an increased amount of cholesterol (mumole per mg protein), whereas actively growing newborn and regenerating livers gave rather lower amounts in comparison with that of normal adult liver."} {"id": "PMID:179990", "title": "Urinary excretion of retinol-binding protein (RBP) in rabbit chronically poisoned with cadmium. Isolation and partial characterization of rabbit RBP.", "content": "Studies were conducted to induce urinary excretion of retinol-binding protein (RBP) in the rabbit by long-term administration of cadmium, and to isolate and characterize rabbit RBP. Two rabbits were exposed to Cd at a dose of 0.8 and/or 1.5mg/kg of body weight by means of subcutaneous injections five times per week. One rabbit excreted large amounts of protein (0.8 to 1.6 g/day) from days 80 to 118. The electrophoretic patterns of the urinary protein showed two fluorescent bands specific for protein-bound retinol in the alpha-region; these were presumed to be RBP. Rabbit RBP was isolated from the pooled urine (10.3 liters) by a sequence of procedures which included gel filtration on Sephadex G-100 and chromatography on DEAE- and SP-Sephadex. Purified RBP (20 mg) was found to be homogeneous by physical and immunological criteria. The RBP had alpha-mobility, with a molecular weight of approximately 20,000. The properties of rabbit RBP resembled those of human RBP simultaneously isolated from the urine of patients with \"Itai-Itai\" disease in many ways: ultraviolet and fluorescence spectra, and amino acid compositions. A monospecific anti-rabbit RBP antiserum was raised in a goat. There was no immunological cross-reactivity between rabbit and human RBP. The molecular size of the retinol-containing protein in fresh rabbit serum was estimated to be about 60,000 to 70,000 by gel filtration on Sephadex G-200. Rabbit RBP in the serum was also shown to be immunologically identical with purified RBP from the urine.", "contents": "Urinary excretion of retinol-binding protein (RBP) in rabbit chronically poisoned with cadmium. Isolation and partial characterization of rabbit RBP. Studies were conducted to induce urinary excretion of retinol-binding protein (RBP) in the rabbit by long-term administration of cadmium, and to isolate and characterize rabbit RBP. Two rabbits were exposed to Cd at a dose of 0.8 and/or 1.5mg/kg of body weight by means of subcutaneous injections five times per week. One rabbit excreted large amounts of protein (0.8 to 1.6 g/day) from days 80 to 118. The electrophoretic patterns of the urinary protein showed two fluorescent bands specific for protein-bound retinol in the alpha-region; these were presumed to be RBP. Rabbit RBP was isolated from the pooled urine (10.3 liters) by a sequence of procedures which included gel filtration on Sephadex G-100 and chromatography on DEAE- and SP-Sephadex. Purified RBP (20 mg) was found to be homogeneous by physical and immunological criteria. The RBP had alpha-mobility, with a molecular weight of approximately 20,000. The properties of rabbit RBP resembled those of human RBP simultaneously isolated from the urine of patients with \"Itai-Itai\" disease in many ways: ultraviolet and fluorescence spectra, and amino acid compositions. A monospecific anti-rabbit RBP antiserum was raised in a goat. There was no immunological cross-reactivity between rabbit and human RBP. The molecular size of the retinol-containing protein in fresh rabbit serum was estimated to be about 60,000 to 70,000 by gel filtration on Sephadex G-200. Rabbit RBP in the serum was also shown to be immunologically identical with purified RBP from the urine."} {"id": "PMID:179992", "title": "Phosphatidylserine synthetase mutants of Escherichia coli. Genetic mapping and membrane phospholipid composition.", "content": "Mutants of Escherichia coli K-12 defective in CDP-diglyceride:L-serine phosphatidyltransferase (phosphatidylserine synthetase) can be isolated by a rapid autoradiographic screening assay described previously (Raetz, C. R. H. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 2274-2278). Four organisms of this kind have now been characterized. The gene (designated pss) which is altered in these mutants is closely linked to the nadB locus near minute 49 on the E. coli chromosome. Strains carrying the pss-8 mutation do not grow at elevated temperatures and have low levels of an altered synthetase in cell extracts. An analysis of several hundred transductants and temperature-resistant revertants reveals that the pss-8 mutation is responsible both for the enzyme defect and for the phenotype. When a pss-8 mutant is shifted to the nonpermissive temperature, the cells stop dividing and form long filaments. After 3 hours at 44 degrees the level of phosphatidylethanolamine drops from 66 to 32% (percentage of the total lipid phosphorus), while the combined levels of phosphatidylglycerol and cardiolipin rise from 34 to 68%.", "contents": "Phosphatidylserine synthetase mutants of Escherichia coli. Genetic mapping and membrane phospholipid composition. Mutants of Escherichia coli K-12 defective in CDP-diglyceride:L-serine phosphatidyltransferase (phosphatidylserine synthetase) can be isolated by a rapid autoradiographic screening assay described previously (Raetz, C. R. H. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 2274-2278). Four organisms of this kind have now been characterized. The gene (designated pss) which is altered in these mutants is closely linked to the nadB locus near minute 49 on the E. coli chromosome. Strains carrying the pss-8 mutation do not grow at elevated temperatures and have low levels of an altered synthetase in cell extracts. An analysis of several hundred transductants and temperature-resistant revertants reveals that the pss-8 mutation is responsible both for the enzyme defect and for the phenotype. When a pss-8 mutant is shifted to the nonpermissive temperature, the cells stop dividing and form long filaments. After 3 hours at 44 degrees the level of phosphatidylethanolamine drops from 66 to 32% (percentage of the total lipid phosphorus), while the combined levels of phosphatidylglycerol and cardiolipin rise from 34 to 68%."} {"id": "PMID:179993", "title": "Restoration of a regulatory response to low density lipoprotein in acid lipase-deficient human fibroblasts.", "content": "Previous studies have shown that cultured fibroblasts derived from patients with genetic defects in lysosomal acid lipase (i. e. the Wolman Syndrome and Cholesteryl Ester Storage Disease) are defective in their ability to hydrolyze the cholesteryl esters contained in plasma low density lipoprotein (LDL). As a result, these mutant cells show a reduced responsiveness to the regulatory actions of LDL, as evidenced by a decreased LDL-mediated suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and by a decreased LDL-mediated activation of cellular cholesteryl ester formation. In the current studies, the Wolman Syndrome and Cholesteryl Ester Storage Disease cells were grown in the same Petri dish with mutant fibroblasts derived from a patient with the homozygous form of Familial Hypercholesterolemia. Whereas pure monolayers of either the Familial Hypercholesterolemia cells (lacking cell surface LDL receptors) or the acid lipase-deficient cells (lacking cholesteryl ester hydrolase activity) responded poorly to LDL, the mixed monolayers developed lipoprotein responsiveness as measured by an enhancement of both LDL-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and LDL-mediated stimulation of cholesteryl ester formation. This effect was shown to result from the release of the lysosomal acid lipase from the Familial Hypercholesterolemia homozygote cells into the culture medium and its subsequent uptake by the acid lipase-deficient cells. The acquisition of this acid lipase activity enhanced the ability of the Wolman Syndrome and Cholesteryl Ester Storage Disease cells to respond to the lipoprotein by suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and activation of cellular cholesteryl ester formation. These data emphasize the importance of the lysosomal acid lipase in the cellular metabolism of LDL cholesteryl esters and, in addition, demonstrate that delivery of this enzyme to genetically deficient cells can enhance the regulatory response to the lipoprotein.", "contents": "Restoration of a regulatory response to low density lipoprotein in acid lipase-deficient human fibroblasts. Previous studies have shown that cultured fibroblasts derived from patients with genetic defects in lysosomal acid lipase (i. e. the Wolman Syndrome and Cholesteryl Ester Storage Disease) are defective in their ability to hydrolyze the cholesteryl esters contained in plasma low density lipoprotein (LDL). As a result, these mutant cells show a reduced responsiveness to the regulatory actions of LDL, as evidenced by a decreased LDL-mediated suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and by a decreased LDL-mediated activation of cellular cholesteryl ester formation. In the current studies, the Wolman Syndrome and Cholesteryl Ester Storage Disease cells were grown in the same Petri dish with mutant fibroblasts derived from a patient with the homozygous form of Familial Hypercholesterolemia. Whereas pure monolayers of either the Familial Hypercholesterolemia cells (lacking cell surface LDL receptors) or the acid lipase-deficient cells (lacking cholesteryl ester hydrolase activity) responded poorly to LDL, the mixed monolayers developed lipoprotein responsiveness as measured by an enhancement of both LDL-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and LDL-mediated stimulation of cholesteryl ester formation. This effect was shown to result from the release of the lysosomal acid lipase from the Familial Hypercholesterolemia homozygote cells into the culture medium and its subsequent uptake by the acid lipase-deficient cells. The acquisition of this acid lipase activity enhanced the ability of the Wolman Syndrome and Cholesteryl Ester Storage Disease cells to respond to the lipoprotein by suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and activation of cellular cholesteryl ester formation. These data emphasize the importance of the lysosomal acid lipase in the cellular metabolism of LDL cholesteryl esters and, in addition, demonstrate that delivery of this enzyme to genetically deficient cells can enhance the regulatory response to the lipoprotein."} {"id": "PMID:179994", "title": "Cell cycle-specific activity of type I and type II cyclic adenosine 3':5'-monophosphate-dependent protein kinases in Chinese hamster ovary cells.", "content": "Types I and II cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinases have been studied during the cell cycle of Chinese hamster ovary cells. Chinese hamster ovary cells were synchronized by selective detachment of mitotic cells from monolayer cultures. Protein kinases were separated by DEAE-cellulose chromatography and were similar to the types of cAMP-dependent protein kinases studied in skeletal muscle and in heart extracts. The total amount of protein kinases activity per cell was substantial, both in mitosis and at the G1/S boundary. During mitosis, the relatively high activity of protein kinase was due to a predominance of type I protein kinase. During early G1, the activity of type I protein kinase decreased and there was little detectable type II activity. A rapid increase in the activity of type II was evident at the G1/S boundary. The administration of puromycin (50 mug/ml) from 1 to 5 hours after selective detachment of mitotic cells abolished the activity of type II cAMP-dependent protein kinase seen at the G1/S border, but had no observable effect on the activity of type I protein kinase. The data presented demonstrate cell cycle-specific activity patterns of type I and type II protein kinase Type I protein kinase activity is high in mitosis and is constant throughout the cell cycle. Increased type II protein kinase activity seems to be related to the initiation of DNA synthesis in S phase. The data suggest a translational control of type II cAMP-dependent protein kinase activity.", "contents": "Cell cycle-specific activity of type I and type II cyclic adenosine 3':5'-monophosphate-dependent protein kinases in Chinese hamster ovary cells. Types I and II cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinases have been studied during the cell cycle of Chinese hamster ovary cells. Chinese hamster ovary cells were synchronized by selective detachment of mitotic cells from monolayer cultures. Protein kinases were separated by DEAE-cellulose chromatography and were similar to the types of cAMP-dependent protein kinases studied in skeletal muscle and in heart extracts. The total amount of protein kinases activity per cell was substantial, both in mitosis and at the G1/S boundary. During mitosis, the relatively high activity of protein kinase was due to a predominance of type I protein kinase. During early G1, the activity of type I protein kinase decreased and there was little detectable type II activity. A rapid increase in the activity of type II was evident at the G1/S boundary. The administration of puromycin (50 mug/ml) from 1 to 5 hours after selective detachment of mitotic cells abolished the activity of type II cAMP-dependent protein kinase seen at the G1/S border, but had no observable effect on the activity of type I protein kinase. The data presented demonstrate cell cycle-specific activity patterns of type I and type II protein kinase Type I protein kinase activity is high in mitosis and is constant throughout the cell cycle. Increased type II protein kinase activity seems to be related to the initiation of DNA synthesis in S phase. The data suggest a translational control of type II cAMP-dependent protein kinase activity."} {"id": "PMID:179996", "title": "Dissociation and reassociation of the phosphorylated and nonphosphorylated forms of adenosine 3':5' -monophosphate-dependent protein kinase from bovine cardiac muscle.", "content": "Adenosine 3':5' -monophosphate (cyclic AMP) -dependent protein kinase from bovine heart muscle catalyzes the phosphorylation of its regulatory, cyclic AMP-binding subunit. Phosphorylation enhances net dissociation of the enzyme by cyclic AMP. Chromatography on omega-aminohexyl-agarose was used to study the effects of phosphorylation on cyclic AMP binding and subunit dissociation and reassociation. This method permitted rapid separation of the catalytic subunit from the cyclic AMP -binding protein and holoenzyme. Phospho- and dephosphoprotein kinases were found to dissociate to the same extent at any given concentration of cyclic AMP and completely at saturation. At equilibrium, the amount of cyclic AMP bound was the same for both forms of enzyme and was directly proportional to the degree of dissociation of the holoenzyme. In the absence of cyclic AMP, phospho- and dephospho-cyclic AMP-binding proteins reassociated completely with the catalytic subunit. However, the rate of reassociation of the dephospho-cyclic AMP-binding protein was at least 5 times greater than the phospho-cyclic AMP-binding protein. Retardation of reassociation was directly proportional to the extent of phosphorylation. We conclude that the degree to which the cyclic AMP-binding protein is phosphorylated markedly affects its intrinsic ability to combine with the catalytic subunit to regenerate the inactive cyclic nucleotide-dependent kinase and that the state of phosphorylation of this subunit may be important in detemining the proportion of dissociated (active) and reassociated (inactive) protein kinase at any given time.", "contents": "Dissociation and reassociation of the phosphorylated and nonphosphorylated forms of adenosine 3':5' -monophosphate-dependent protein kinase from bovine cardiac muscle. Adenosine 3':5' -monophosphate (cyclic AMP) -dependent protein kinase from bovine heart muscle catalyzes the phosphorylation of its regulatory, cyclic AMP-binding subunit. Phosphorylation enhances net dissociation of the enzyme by cyclic AMP. Chromatography on omega-aminohexyl-agarose was used to study the effects of phosphorylation on cyclic AMP binding and subunit dissociation and reassociation. This method permitted rapid separation of the catalytic subunit from the cyclic AMP -binding protein and holoenzyme. Phospho- and dephosphoprotein kinases were found to dissociate to the same extent at any given concentration of cyclic AMP and completely at saturation. At equilibrium, the amount of cyclic AMP bound was the same for both forms of enzyme and was directly proportional to the degree of dissociation of the holoenzyme. In the absence of cyclic AMP, phospho- and dephospho-cyclic AMP-binding proteins reassociated completely with the catalytic subunit. However, the rate of reassociation of the dephospho-cyclic AMP-binding protein was at least 5 times greater than the phospho-cyclic AMP-binding protein. Retardation of reassociation was directly proportional to the extent of phosphorylation. We conclude that the degree to which the cyclic AMP-binding protein is phosphorylated markedly affects its intrinsic ability to combine with the catalytic subunit to regenerate the inactive cyclic nucleotide-dependent kinase and that the state of phosphorylation of this subunit may be important in detemining the proportion of dissociated (active) and reassociated (inactive) protein kinase at any given time."} {"id": "PMID:179997", "title": "Modification of Escherichia coli DNA ligase by cleavage with trypsin.", "content": "Limited treatment of Escherichia coli DNA ligase with trypsin results in rapid loss of DNA joining activity. However, the ability to react with DPN to form the covalent enzyme-AMP intermediate is unaffected. The cleaved enzyme is also unable to catalyze the formation of DNA-adenylate, the second covalent intermediate in the ligase-catalyzed reaction. These findings demonstrate that portions of the DNA ligase molecule that are required for phosphodiester bond formation are not required for at least one of the partial reactions catalyzed by this enzyme.", "contents": "Modification of Escherichia coli DNA ligase by cleavage with trypsin. Limited treatment of Escherichia coli DNA ligase with trypsin results in rapid loss of DNA joining activity. However, the ability to react with DPN to form the covalent enzyme-AMP intermediate is unaffected. The cleaved enzyme is also unable to catalyze the formation of DNA-adenylate, the second covalent intermediate in the ligase-catalyzed reaction. These findings demonstrate that portions of the DNA ligase molecule that are required for phosphodiester bond formation are not required for at least one of the partial reactions catalyzed by this enzyme."} {"id": "PMID:179998", "title": "Nucleotide sequence of 5 S ribosomal RNA precursor from Bacillus subtilis.", "content": "The complete nucleotide sequence of a 179-nucleotide precursor (p5A) of 5 S ribosomal RNA from Bacillus subtilis is presented. In addition to the 116-nucleotide mature segment, the p5A molecule contains 21 additional nucleotides at its 5' end and 42 at its 3' terminus. Structural features within the p5A molecule which possibly interact with a specific maturation endonuclease (RNase M5) are identifiable. These include 2-fold rotational symmetry about the cleavage sites, which may approximately place the p5A molecule on the RNase M5 surface, and translational (positional) symmetry, which may precisely orient substrate phosphodiester bonds with respect to catalytic amino acids. Certain features of the 3' -terminal, precursor-specific portion of p5A possibly are involved in the termination of DNA transcription.", "contents": "Nucleotide sequence of 5 S ribosomal RNA precursor from Bacillus subtilis. The complete nucleotide sequence of a 179-nucleotide precursor (p5A) of 5 S ribosomal RNA from Bacillus subtilis is presented. In addition to the 116-nucleotide mature segment, the p5A molecule contains 21 additional nucleotides at its 5' end and 42 at its 3' terminus. Structural features within the p5A molecule which possibly interact with a specific maturation endonuclease (RNase M5) are identifiable. These include 2-fold rotational symmetry about the cleavage sites, which may approximately place the p5A molecule on the RNase M5 surface, and translational (positional) symmetry, which may precisely orient substrate phosphodiester bonds with respect to catalytic amino acids. Certain features of the 3' -terminal, precursor-specific portion of p5A possibly are involved in the termination of DNA transcription."} {"id": "PMID:179999", "title": "The kinetic mechanism of rat kidney gamma-glutamylcysteine synthetase.", "content": "A detailed kinetic investigation was made of the binding mechanism of gamma-glutamylcysteine synthetase purified from rat kidney. The results of initial rate and inhibition studies are consistent with a partially random mechanism in which ATP is the obligatory first substrate and both amino acids bind in a random order to the enzyme-ATP complex. Formation of the enzyme-substrate quaternary complex is necessary prior to release of products. This mechanism is consistent with previous binding studies with the enzyme and while it does not rule out participation of enzyme-bound gamma-glutamyl phosphate as an intermediate in catalysis, such an intermediate cannot be a discrete covalent complex.", "contents": "The kinetic mechanism of rat kidney gamma-glutamylcysteine synthetase. A detailed kinetic investigation was made of the binding mechanism of gamma-glutamylcysteine synthetase purified from rat kidney. The results of initial rate and inhibition studies are consistent with a partially random mechanism in which ATP is the obligatory first substrate and both amino acids bind in a random order to the enzyme-ATP complex. Formation of the enzyme-substrate quaternary complex is necessary prior to release of products. This mechanism is consistent with previous binding studies with the enzyme and while it does not rule out participation of enzyme-bound gamma-glutamyl phosphate as an intermediate in catalysis, such an intermediate cannot be a discrete covalent complex."} {"id": "PMID:180000", "title": "Differential response to adrenocorticotropic hormone analogs of bovine adrenal plasma membranes and cells.", "content": "The ability of three analogs of ACTH1-24 ([Gln5, Phe9] ACTH1-24, [Gln5, Ala9[Acth1-24, and [Gln5, Lys8, Phe9[ ACTH1-24) embodying tryptophan substitutions to activate the adenylate cyclase system of a bovine adrenal plasma membrane preparation was compared to the effect of the analogs on adenosine 3':5'-monophosphate (cyclic AMP) accumulation and steroidogenesis in viable bovine adrenocortical cells. The results were not comparable. Whereas the analogs antagonized the ACTH1-24-activated membrane cyclase they stimulated cyclic AMP accumulation as well as steroid production of the cells. None of the analogs inhibited steroidogenesis of ACTH1-24-stimulated cells, but two of them, at very high dose levels, inhibited cyclic AMP production. The ability of the analogs to stimulate steroidogenesis of the adrenal cells half-maximally decreased in the order tryptophan greater than phenylalanine greater than alanine, indicating that the aromaticity of the indole ring of tryptophan is necessary for maximal interaction between hormone and receptor. Both the absolute and relative steroidogenic potencies were the same for several analogs when assayed with rat adrenal cells. Although only a small fraction of the cell's potential to produce cyclic AMP was necessary to induce maximum steroid production, the relative activities of a series of analogs were the same for steroidogenesis as for cyclic AMP accumulation. Furthermore, the concentration of cyclic AMP necessary for full steroidogenesis was practically identical for a series of peptides that differed widely in potency. These findings support the postulate that cyclic AMP accumulation and steroidogenesis in adrenocortical cells are coupled processes. The differential behavior of bovine adrenal plasma membranes and bovine adrenocortical cells toward ACTH analogs indicates that structure-function studies using cyclase assays may not reflect events that take place in the intact adrenal or in cell preparations derived therefrom.", "contents": "Differential response to adrenocorticotropic hormone analogs of bovine adrenal plasma membranes and cells. The ability of three analogs of ACTH1-24 ([Gln5, Phe9] ACTH1-24, [Gln5, Ala9[Acth1-24, and [Gln5, Lys8, Phe9[ ACTH1-24) embodying tryptophan substitutions to activate the adenylate cyclase system of a bovine adrenal plasma membrane preparation was compared to the effect of the analogs on adenosine 3':5'-monophosphate (cyclic AMP) accumulation and steroidogenesis in viable bovine adrenocortical cells. The results were not comparable. Whereas the analogs antagonized the ACTH1-24-activated membrane cyclase they stimulated cyclic AMP accumulation as well as steroid production of the cells. None of the analogs inhibited steroidogenesis of ACTH1-24-stimulated cells, but two of them, at very high dose levels, inhibited cyclic AMP production. The ability of the analogs to stimulate steroidogenesis of the adrenal cells half-maximally decreased in the order tryptophan greater than phenylalanine greater than alanine, indicating that the aromaticity of the indole ring of tryptophan is necessary for maximal interaction between hormone and receptor. Both the absolute and relative steroidogenic potencies were the same for several analogs when assayed with rat adrenal cells. Although only a small fraction of the cell's potential to produce cyclic AMP was necessary to induce maximum steroid production, the relative activities of a series of analogs were the same for steroidogenesis as for cyclic AMP accumulation. Furthermore, the concentration of cyclic AMP necessary for full steroidogenesis was practically identical for a series of peptides that differed widely in potency. These findings support the postulate that cyclic AMP accumulation and steroidogenesis in adrenocortical cells are coupled processes. The differential behavior of bovine adrenal plasma membranes and bovine adrenocortical cells toward ACTH analogs indicates that structure-function studies using cyclase assays may not reflect events that take place in the intact adrenal or in cell preparations derived therefrom."} {"id": "PMID:180001", "title": "Infulence of hormones and medium composition on the degradation of phosphoenolpyruvate carboxykinase (GTP) and total protein in Reuber H35 cells.", "content": "Reuber H35 cells were pulse-labeled with radioactive leucine and the influence of hormones, serum, and amino acids on protein degradation was investigated during a subsequent chase period. Radioactive, immunoprecipitable phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) had a half-life of 5 to 6 hours which was not influenced by either N6, O2-dibutyryl adenosine 3':5'-monophosphate, dexamethasone, or insulin. The rate of phosphoenolpyruvate carboxykinase degradation was the same under steady state conditions as during the approach to a new steady state following hormonal induction or deinduction of the enzyme. Therefore, hormonal regulation of enzyme activity in vivo is the result of changes in the rate of enzyme synthesis. The rate of proteolysis for total cell proteins was increased under nutritional step-down conditions produced by the removal of serum or amino acids, or both, from the medium. This effect was completely prevented by insulin. Cycloheximide and puromycin, but not actinomycin D or cordycepin, inhibited protein degradation under step-down conditions but did not further decrease the basal rate of proteolysis measured in the presence of either insulin or serum plus amino acids. There was a good correlation between changes in proteolysis produced by serum and amino acids and changes in the degradation rate of phosphoenolpyruvate carboxykinase. Also, inhibition of proteolysis with cycloheximide and puromycin was accompanied by a decrease in the degradation rate for enzyme antigen. It is suggested that nutritional step-down leads either to the synthesis or activation of a proteolytic system.", "contents": "Infulence of hormones and medium composition on the degradation of phosphoenolpyruvate carboxykinase (GTP) and total protein in Reuber H35 cells. Reuber H35 cells were pulse-labeled with radioactive leucine and the influence of hormones, serum, and amino acids on protein degradation was investigated during a subsequent chase period. Radioactive, immunoprecipitable phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) had a half-life of 5 to 6 hours which was not influenced by either N6, O2-dibutyryl adenosine 3':5'-monophosphate, dexamethasone, or insulin. The rate of phosphoenolpyruvate carboxykinase degradation was the same under steady state conditions as during the approach to a new steady state following hormonal induction or deinduction of the enzyme. Therefore, hormonal regulation of enzyme activity in vivo is the result of changes in the rate of enzyme synthesis. The rate of proteolysis for total cell proteins was increased under nutritional step-down conditions produced by the removal of serum or amino acids, or both, from the medium. This effect was completely prevented by insulin. Cycloheximide and puromycin, but not actinomycin D or cordycepin, inhibited protein degradation under step-down conditions but did not further decrease the basal rate of proteolysis measured in the presence of either insulin or serum plus amino acids. There was a good correlation between changes in proteolysis produced by serum and amino acids and changes in the degradation rate of phosphoenolpyruvate carboxykinase. Also, inhibition of proteolysis with cycloheximide and puromycin was accompanied by a decrease in the degradation rate for enzyme antigen. It is suggested that nutritional step-down leads either to the synthesis or activation of a proteolytic system."} {"id": "PMID:180002", "title": "NAD+-malic enzyme. Regulatory properties of the enzyme from Ascaris suum.", "content": "The regulatory properties of the NAD-dependent malic enzyme from the mitochondria of Ascaris suum have been studied. The malate saturation curve exhibits sigmoidicity and the degree of this sigmoidicity increases as the pH is increased. Fumarate was the only compound tested that stimulated the enzyme activity, whereas oxalacetate was the most powerful inhibitor. Activation by low levels of fumarate was found to be competitive with malate. It is proposed that this stimulation has physiological significance in controlling the dismutation reaction in the parasite. The branched-chain volatile fatty acid excretion products, tiglate, 2-methylbutanoate, and 2-methylpentanoate, inhibited the enzyme activity and this inhibition was competitive with malate. The Ki values for these compounds are in the physiological range of their concentrations; therefore, it is suggested that they may aid in controlling the malic enzyme activity in vivo. Oxalacetate inhibition of malic enzyme activity was competitive with malate, and the Ki values decreased with an increase in pH. Two alternatives are proposed which could account for the lack of oxalacetate decarboxylation by the ascarid malic enzyme.", "contents": "NAD+-malic enzyme. Regulatory properties of the enzyme from Ascaris suum. The regulatory properties of the NAD-dependent malic enzyme from the mitochondria of Ascaris suum have been studied. The malate saturation curve exhibits sigmoidicity and the degree of this sigmoidicity increases as the pH is increased. Fumarate was the only compound tested that stimulated the enzyme activity, whereas oxalacetate was the most powerful inhibitor. Activation by low levels of fumarate was found to be competitive with malate. It is proposed that this stimulation has physiological significance in controlling the dismutation reaction in the parasite. The branched-chain volatile fatty acid excretion products, tiglate, 2-methylbutanoate, and 2-methylpentanoate, inhibited the enzyme activity and this inhibition was competitive with malate. The Ki values for these compounds are in the physiological range of their concentrations; therefore, it is suggested that they may aid in controlling the malic enzyme activity in vivo. Oxalacetate inhibition of malic enzyme activity was competitive with malate, and the Ki values decreased with an increase in pH. Two alternatives are proposed which could account for the lack of oxalacetate decarboxylation by the ascarid malic enzyme."} {"id": "PMID:180003", "title": "Asparagusate dehydrogenases and lipoyl dehydrogenase from asparagus mitochondria. Physical, chemical, and enzymatic properties.", "content": "Asparagusate dehydrogenases I and II and lipoyl dehydrogenase have been obtained in homogeneous state from asparagus mitochondria. They are flavin enzymes with 1 mol of FAD/mol of protein. Asparagusate dehydrogenases I and II and lipoyl dehydrogenase have s20,w of 6.22 S, 6.39 S, and 5.91 S, respectively, and molecular weights of 111,000, 110,000, and 95,000 (sedimentation equilibrium) or 112,000, 112,000, and 92,000 (gel filtration). They are slightly acidic proteins with isoelectric points of 6.75, 5.75, and 6.80. Both asparagusate dehydrogenases catalyzed the reaction Asg(SH)2 + NAD+ equilibrium AsgS2 + NADH + H+ and exhibit lipoyl dehydrogenase and diaphorase activities. Lipoyl dehydrogenase is specific for lipoate and has no asparagusate dehydrogenase activity. NADP cannot replace NAD in any case. Optimum pH for substrate reduction of the three enzymes are near 5.9. Asparagusate dehydrogenases I and II have Km values of 21.5 mM and 20.0 mM for asparagusate and 3.0 mM and 3.3 mM for lipoate, respectively. Lipoyl dehydrogenase activity of asparagusate dehydrogenases is enhanced by NAD and surfactants such as lecithin and Tween 80, but asparagusate dehydrogenase activity is not enhanced. Asparagusate dehydrogenases are strongly inhibited by mercuric ion, p-chloromercuribenzoic acid, and N-ethylmaleimide. Amino acid composition of the three enzymes is presented and discussed.", "contents": "Asparagusate dehydrogenases and lipoyl dehydrogenase from asparagus mitochondria. Physical, chemical, and enzymatic properties. Asparagusate dehydrogenases I and II and lipoyl dehydrogenase have been obtained in homogeneous state from asparagus mitochondria. They are flavin enzymes with 1 mol of FAD/mol of protein. Asparagusate dehydrogenases I and II and lipoyl dehydrogenase have s20,w of 6.22 S, 6.39 S, and 5.91 S, respectively, and molecular weights of 111,000, 110,000, and 95,000 (sedimentation equilibrium) or 112,000, 112,000, and 92,000 (gel filtration). They are slightly acidic proteins with isoelectric points of 6.75, 5.75, and 6.80. Both asparagusate dehydrogenases catalyzed the reaction Asg(SH)2 + NAD+ equilibrium AsgS2 + NADH + H+ and exhibit lipoyl dehydrogenase and diaphorase activities. Lipoyl dehydrogenase is specific for lipoate and has no asparagusate dehydrogenase activity. NADP cannot replace NAD in any case. Optimum pH for substrate reduction of the three enzymes are near 5.9. Asparagusate dehydrogenases I and II have Km values of 21.5 mM and 20.0 mM for asparagusate and 3.0 mM and 3.3 mM for lipoate, respectively. Lipoyl dehydrogenase activity of asparagusate dehydrogenases is enhanced by NAD and surfactants such as lecithin and Tween 80, but asparagusate dehydrogenase activity is not enhanced. Asparagusate dehydrogenases are strongly inhibited by mercuric ion, p-chloromercuribenzoic acid, and N-ethylmaleimide. Amino acid composition of the three enzymes is presented and discussed."} {"id": "PMID:180004", "title": "Reversible inactivation of phenylalanine hydroxylase by catecholamines in cultured hepatoma cells.", "content": "Phenylalanine hydroxylase in Reuber H4 hepatoma cell cultures can be rapidly inactivated by the addition of epinephrine, norepinephrine, dopamine, or 3,4-dihydroxyphenylalanine, in order of decreasing effectiveness, to the culture medium. The enzyme was 50% inactivated in 1 hour by 25 muM (R)-epinephrine or 45 muM (R)-norepinephrine in the medium. High concentrations of epinephrine caused a 70% inactivation in 15 min. Phenylalanine hydroxylase appears to be reversibly inactivated by epinephrine within the cells; since washing the compound off the cell cultures resulted in a rapid restoration of enzyme activity (40% in 1 hour), cycloheximide had little effect on the initial rate of recovery of enzyme activity and the same amount of phenylalanine hydroxylase antigen per cell was isolated from treated and normal cultures. Both (S)- and (R)-epinephrine inactivated the enzyme, and 0.1 mM desmethylimipramine, an inhibitor of amine transport, significantly decreased the effect of epinephrine on the hydroxylase activity. The possibility, suggested by the above results, that epinephrine might be directly inactivating phenylalanine hydroxylase within the cells was supported by the finding that purified rat liver phenylalanine hydroxylase would be 50% inactivated by 1.5 muM epinephrine in 10 min.", "contents": "Reversible inactivation of phenylalanine hydroxylase by catecholamines in cultured hepatoma cells. Phenylalanine hydroxylase in Reuber H4 hepatoma cell cultures can be rapidly inactivated by the addition of epinephrine, norepinephrine, dopamine, or 3,4-dihydroxyphenylalanine, in order of decreasing effectiveness, to the culture medium. The enzyme was 50% inactivated in 1 hour by 25 muM (R)-epinephrine or 45 muM (R)-norepinephrine in the medium. High concentrations of epinephrine caused a 70% inactivation in 15 min. Phenylalanine hydroxylase appears to be reversibly inactivated by epinephrine within the cells; since washing the compound off the cell cultures resulted in a rapid restoration of enzyme activity (40% in 1 hour), cycloheximide had little effect on the initial rate of recovery of enzyme activity and the same amount of phenylalanine hydroxylase antigen per cell was isolated from treated and normal cultures. Both (S)- and (R)-epinephrine inactivated the enzyme, and 0.1 mM desmethylimipramine, an inhibitor of amine transport, significantly decreased the effect of epinephrine on the hydroxylase activity. The possibility, suggested by the above results, that epinephrine might be directly inactivating phenylalanine hydroxylase within the cells was supported by the finding that purified rat liver phenylalanine hydroxylase would be 50% inactivated by 1.5 muM epinephrine in 10 min."} {"id": "PMID:180005", "title": "Mechanism of inactivation of phenylalanine hydroxylase by p-chlorophenylalanine in hepatome cells in culture. Two possible models.", "content": "The mechanism by which p-chlorophenylalanine specifically reduces phenylalanine hydroxylase activity in rat liver in vivo and in Reuber H4 hepatoma cells in culture has been investigated. Chromatography on hydroxylapatite of liver extract from rats injected with p-chlorophenylalanine showed that the compound differentially affected the three normal phenylalanine hydroxylase isoenzymes (I, II, and III); isoenzymes II and III were completely absent after the treatment, but isoenzyme I was only reduced in quantity compared with normal adult rats. Normal Reuber H4 cells only possess isoenzyme I; treatment with p-chlorophenylalanine yielded a reduced level of enzyme activity which appeared to be noraml isoenzyme I by both chromatographic and kinetic criteria. There is evidence, based on immunochemical techniques, that cultures grown in the presence of p-chlorophenylalanine have significantly reduced levels of phenylalanine hydroxylase antigen, and that p-chlorophenylalanine inactivates phenylalanine hydroxylase at or near the time of enzyme synthesis. The bulk of enzyme synthesized prior to the addition of the compound appears unaffected by it. There is no indication that protein synthesis itself is affected by p-chlorophenylalanine. In addition, p-chlorophenylacetate was found to inactivate phenylalanine hydroxylase in an apparently identical manner with p-chlorophenylalanine, which almost certainly eliminates from consideration any mechanism of inactivation specifically requiring an amino acid. Finally, effects of cycloheximide and chlorophenylalanine were compared. Taken together, the data lead to two possible models for the inactivation of the enzyme. The model most consistent with all data requires (predicts) the existence of a proenzyme form of phenylalanine hydroxylase which can be specifically inactivated by p-chlorophenylalanine.", "contents": "Mechanism of inactivation of phenylalanine hydroxylase by p-chlorophenylalanine in hepatome cells in culture. Two possible models. The mechanism by which p-chlorophenylalanine specifically reduces phenylalanine hydroxylase activity in rat liver in vivo and in Reuber H4 hepatoma cells in culture has been investigated. Chromatography on hydroxylapatite of liver extract from rats injected with p-chlorophenylalanine showed that the compound differentially affected the three normal phenylalanine hydroxylase isoenzymes (I, II, and III); isoenzymes II and III were completely absent after the treatment, but isoenzyme I was only reduced in quantity compared with normal adult rats. Normal Reuber H4 cells only possess isoenzyme I; treatment with p-chlorophenylalanine yielded a reduced level of enzyme activity which appeared to be noraml isoenzyme I by both chromatographic and kinetic criteria. There is evidence, based on immunochemical techniques, that cultures grown in the presence of p-chlorophenylalanine have significantly reduced levels of phenylalanine hydroxylase antigen, and that p-chlorophenylalanine inactivates phenylalanine hydroxylase at or near the time of enzyme synthesis. The bulk of enzyme synthesized prior to the addition of the compound appears unaffected by it. There is no indication that protein synthesis itself is affected by p-chlorophenylalanine. In addition, p-chlorophenylacetate was found to inactivate phenylalanine hydroxylase in an apparently identical manner with p-chlorophenylalanine, which almost certainly eliminates from consideration any mechanism of inactivation specifically requiring an amino acid. Finally, effects of cycloheximide and chlorophenylalanine were compared. Taken together, the data lead to two possible models for the inactivation of the enzyme. The model most consistent with all data requires (predicts) the existence of a proenzyme form of phenylalanine hydroxylase which can be specifically inactivated by p-chlorophenylalanine."} {"id": "PMID:180006", "title": "Phosphorylation of distinct regions of f1 histone. Relationship to the cell cycle.", "content": "The phosphorylation of different amino acids in distinct regions of f1 histone was studied in highly synchronized Chinese hamster cell populations (line CHO). The purified, 32P-labeled f1 histone was bisected into NH2-terminal and COOH-terminal fragments with N-bromosuccinimide. Tryptic phosphopeptides from these fragments were resolved using sequential high voltage electrophoretic steps on paper. No phosphorylation was observed in early G1-arrested cells. Interphase phosphorylation began in late G1 in the COOH-terminal portion of the molecule on serine. This event continued throughout S phase and persisted into mitosis. However, in mitosis additional phosphorylation was observed in the COOH-terminal portion of the molecule on threonine, and for the only time in the CHO cell cycle the NH2-terminal portion of the molecule was also phosphorylated on both serine and threonine. The peptide studies thus predicted that a minimum of four sites (two serine and two threonine) were phosphorylated in the f1 histone of mitotic CHO cells. This was confirmed using electrophoresis in long polyacrylamide gels.", "contents": "Phosphorylation of distinct regions of f1 histone. Relationship to the cell cycle. The phosphorylation of different amino acids in distinct regions of f1 histone was studied in highly synchronized Chinese hamster cell populations (line CHO). The purified, 32P-labeled f1 histone was bisected into NH2-terminal and COOH-terminal fragments with N-bromosuccinimide. Tryptic phosphopeptides from these fragments were resolved using sequential high voltage electrophoretic steps on paper. No phosphorylation was observed in early G1-arrested cells. Interphase phosphorylation began in late G1 in the COOH-terminal portion of the molecule on serine. This event continued throughout S phase and persisted into mitosis. However, in mitosis additional phosphorylation was observed in the COOH-terminal portion of the molecule on threonine, and for the only time in the CHO cell cycle the NH2-terminal portion of the molecule was also phosphorylated on both serine and threonine. The peptide studies thus predicted that a minimum of four sites (two serine and two threonine) were phosphorylated in the f1 histone of mitotic CHO cells. This was confirmed using electrophoresis in long polyacrylamide gels."} {"id": "PMID:180007", "title": "Regulation of receptor concentration by homologous hormone. Effect of human growth hormone on its receptor in IM-9 lymphocytes.", "content": "When cultured human lymphocytes of the IM-9 line were exposed to human growth hormone (hGH) at 37 degrees, washed for 2 hours, and incubated with 125I-hGH, the binding of 125I-hGH was reduced. The magnitude of the reduction in binding was dependent on the concentration of growth hormone present as well as the duration of the exposure. As little as 2 X 10(-11) M (0.5 ng/ml) growth hormone had a discernible effect. Growth hormone at 2 X 10(-10) M (5.0 ng/ml), which is a low resting concentration of hormone in vivo and occupies about 20% of the receptors at steady state at 30 degrees, produced a 50% reduction in binding while 20 mg/ml, which occupies about 50% of the receptors under steady state conditions, produced an 80% loss of receptors. Further increases in growth hormone concentration produced little further effect on receptor loss. Thus, the loss of receptors at a given concentration of growth hormone (up to 20 ng/ml) in the preincubation at 37 degrees was greater than the occupancy produced by that concentration of growth hormone receptors under steady state conditions at 30 degrees. Analysis of the data indicated that the decrease in binding of 125I-hGH was due to a loss of receptors per cell without any change in affinity of receptor for hormone or in cell number. The concentration of insulin receptors on these cells was affected by the insulin concentration in the medium, and the concentration of growth hormone receptors was affected by growth hormone, but neither hormone had any effect on the heterologous receptors. Exposure of the cells to cycloheximide (0.1 mM) produced a progressive but smaller loss of growth hormone receptors, and the effect of cycloheximide was additive to the receptor loss induced by growth hormone, suggesting that cycloheximide inhibited synthesis of receptors while growth hormone accelerated loss of receptors. When growth hormone was removed from the medium, receptor concentrations were restored rapidly; half of the loss was restored by 6 to 8 hours and the full complement of receptors was restored by 24 hours following removal of the hormone. If the growth hormone was removed and replaced with cycloheximide, the return of the receptors was delayed until the cycloheximide was removed. Thus restoration of the receptors appeared to require the synthesis of new proteins. These data indicate that in the IM-9 lymphocytes the concentration of growth hormone receptors is very sensitive to regulation by growth hormone and also add further support to the suggestion that hormones in general actively regulate the concentration of their own receptors.", "contents": "Regulation of receptor concentration by homologous hormone. Effect of human growth hormone on its receptor in IM-9 lymphocytes. When cultured human lymphocytes of the IM-9 line were exposed to human growth hormone (hGH) at 37 degrees, washed for 2 hours, and incubated with 125I-hGH, the binding of 125I-hGH was reduced. The magnitude of the reduction in binding was dependent on the concentration of growth hormone present as well as the duration of the exposure. As little as 2 X 10(-11) M (0.5 ng/ml) growth hormone had a discernible effect. Growth hormone at 2 X 10(-10) M (5.0 ng/ml), which is a low resting concentration of hormone in vivo and occupies about 20% of the receptors at steady state at 30 degrees, produced a 50% reduction in binding while 20 mg/ml, which occupies about 50% of the receptors under steady state conditions, produced an 80% loss of receptors. Further increases in growth hormone concentration produced little further effect on receptor loss. Thus, the loss of receptors at a given concentration of growth hormone (up to 20 ng/ml) in the preincubation at 37 degrees was greater than the occupancy produced by that concentration of growth hormone receptors under steady state conditions at 30 degrees. Analysis of the data indicated that the decrease in binding of 125I-hGH was due to a loss of receptors per cell without any change in affinity of receptor for hormone or in cell number. The concentration of insulin receptors on these cells was affected by the insulin concentration in the medium, and the concentration of growth hormone receptors was affected by growth hormone, but neither hormone had any effect on the heterologous receptors. Exposure of the cells to cycloheximide (0.1 mM) produced a progressive but smaller loss of growth hormone receptors, and the effect of cycloheximide was additive to the receptor loss induced by growth hormone, suggesting that cycloheximide inhibited synthesis of receptors while growth hormone accelerated loss of receptors. When growth hormone was removed from the medium, receptor concentrations were restored rapidly; half of the loss was restored by 6 to 8 hours and the full complement of receptors was restored by 24 hours following removal of the hormone. If the growth hormone was removed and replaced with cycloheximide, the return of the receptors was delayed until the cycloheximide was removed. Thus restoration of the receptors appeared to require the synthesis of new proteins. These data indicate that in the IM-9 lymphocytes the concentration of growth hormone receptors is very sensitive to regulation by growth hormone and also add further support to the suggestion that hormones in general actively regulate the concentration of their own receptors."} {"id": "PMID:180008", "title": "Hepatic pyruvate kinase. Regulation by glucagon, cyclic adenosine 3'-5'-monophosphate, and insulin in the perfused rat liver.", "content": "A reversible interconversion of two kinetically distinct forms of hepatic pyruvate kinase regulated by glucagon and insulin is demonstrated in the perfused rat liver. The regulation does not involve the total enzyme content of the liver, but rather results in a modulation of the substrate dependence. The forms of pyruvate kinase in liver homogenates are distinguished by measurements of the ratio of the enzyme activity at a subsaturating concentration of P-enolpyruvate (1.3 mM) to the activity at a saturating concentration of this substrate (6.6 mM). A low ratio form of pyruvate kinase (ratio between 0.1 and 0.2) is obtained from livers perfused with 10(-7) M glucagon or 0.1 mM adenosine 3':5'-monophosphate (cyclic AMP). A high ratio form of the enzyme is obtained from livers perfused with no hormone (ratio = 0.35 to 0.45). The regulation of pyruvate kinase by glucagon and cyclic AMP occurs within 2 min following the hormone addition to the liver. Insulin (22 milliunits/ml) counteracts the inhibition of pyruvate kinase caused by 5 X 10(-11) M glucagon, but has only a slight influence on the enzyme properties in the absence of the hyperglycemic hormone. The low ratio form of pyruvate kinase obtained from livers perfused with glucagon or cyclic AMP is unstable in liver extracts and will revert to a high ratio form within 10 min at 37 degrees or within a few hours at 0 degrees. Pyruvate kinase is quantitatively precipitated from liver supernatants with 2.5 M ammonium sulfate. This precipitation stabilizes the enzyme and preserves the kinetically distinguishable forms. The kinetic properties of the two forms of rat hepatic pyruvate kinase are examined using ammonium sulfate precipitates from the perfused rat liver. At pH 7.5 the high ratio form of the enzyme has [S]0.5 = 1.6 +/- 0.2 mM P-enolpyruvate (n = 8). The low ratio form of enzyme from livers perfused with glucagon or cyclic AMP has [S]0.5 = 2.5 +/- 0.4 mM P-enolpyruvate (n = 8). The modification of pyruvate kinase induced by glucagon does not alter the dependence of the enzyme activity on ADP (Km is approximately 0.5 mM ADP for both forms of the enzyme). Both forms are allosterically modulated by fructose 1,6-bisphosphate, L-alanine, and ATP. The changes in the kinetic properties of hepatic pyruvate kinase which follow treating the perfused rat liver with glucagon or cyclic AMP are consistent with the changes observed in the enzyme properties upon phosphorylation in vitro by a clyclic AMP-stimulated protein kinase (Ljungstr\u00f6m, O., Hjelmquist, G. and Engstr\u00f6m, L. (1974) Biochim. Biophys. Acta 358, 289--298). However, other factors also influence the enzyme activity in a similar manner and it remains to be demonstrated that the regulation of hepatic pyruvate kinase by glucagon and cyclic AMP in vivo involes a phosphorylation.", "contents": "Hepatic pyruvate kinase. Regulation by glucagon, cyclic adenosine 3'-5'-monophosphate, and insulin in the perfused rat liver. A reversible interconversion of two kinetically distinct forms of hepatic pyruvate kinase regulated by glucagon and insulin is demonstrated in the perfused rat liver. The regulation does not involve the total enzyme content of the liver, but rather results in a modulation of the substrate dependence. The forms of pyruvate kinase in liver homogenates are distinguished by measurements of the ratio of the enzyme activity at a subsaturating concentration of P-enolpyruvate (1.3 mM) to the activity at a saturating concentration of this substrate (6.6 mM). A low ratio form of pyruvate kinase (ratio between 0.1 and 0.2) is obtained from livers perfused with 10(-7) M glucagon or 0.1 mM adenosine 3':5'-monophosphate (cyclic AMP). A high ratio form of the enzyme is obtained from livers perfused with no hormone (ratio = 0.35 to 0.45). The regulation of pyruvate kinase by glucagon and cyclic AMP occurs within 2 min following the hormone addition to the liver. Insulin (22 milliunits/ml) counteracts the inhibition of pyruvate kinase caused by 5 X 10(-11) M glucagon, but has only a slight influence on the enzyme properties in the absence of the hyperglycemic hormone. The low ratio form of pyruvate kinase obtained from livers perfused with glucagon or cyclic AMP is unstable in liver extracts and will revert to a high ratio form within 10 min at 37 degrees or within a few hours at 0 degrees. Pyruvate kinase is quantitatively precipitated from liver supernatants with 2.5 M ammonium sulfate. This precipitation stabilizes the enzyme and preserves the kinetically distinguishable forms. The kinetic properties of the two forms of rat hepatic pyruvate kinase are examined using ammonium sulfate precipitates from the perfused rat liver. At pH 7.5 the high ratio form of the enzyme has [S]0.5 = 1.6 +/- 0.2 mM P-enolpyruvate (n = 8). The low ratio form of enzyme from livers perfused with glucagon or cyclic AMP has [S]0.5 = 2.5 +/- 0.4 mM P-enolpyruvate (n = 8). The modification of pyruvate kinase induced by glucagon does not alter the dependence of the enzyme activity on ADP (Km is approximately 0.5 mM ADP for both forms of the enzyme). Both forms are allosterically modulated by fructose 1,6-bisphosphate, L-alanine, and ATP. The changes in the kinetic properties of hepatic pyruvate kinase which follow treating the perfused rat liver with glucagon or cyclic AMP are consistent with the changes observed in the enzyme properties upon phosphorylation in vitro by a clyclic AMP-stimulated protein kinase (Ljungstr\u00f6m, O., Hjelmquist, G. and Engstr\u00f6m, L. (1974) Biochim. Biophys. Acta 358, 289--298). However, other factors also influence the enzyme activity in a similar manner and it remains to be demonstrated that the regulation of hepatic pyruvate kinase by glucagon and cyclic AMP in vivo involes a phosphorylation."} {"id": "PMID:180010", "title": "Structure of high density lipoprotein. The immunologic reactivities of the COOH- and NH2-terminal regions of apolipoprotein A-I.", "content": "Only 5 to 10% of the apolipoprotein A-I (ApoA-I) of intact high density lipoprotein (HDL) is detectable by radioimmunoassay. In addition, when isolated ApoA-I is recombined with lipids in vitro, its immunologic reactivity is decreased by 30 to 95%. Thus, ApoA-I is less reactive immunologically in the presence of lipids. Our aim was to ascertain whether the COOH- or NH2-terminal regions of ApoA-I were equally reactive in intact HDL2. CNBr fragments of ApoA-I were produced by the method of Baker et al. (Baker, H.N., Jackson, R.L., and Gotto, A.M. (1973) Biochemistry 12, 3866-3871) and iodinated with lactoperoxidase. Double-antibody radioimmunoassays were set up using anti ApoA-I antisera and 125I-CNBr I (COOH-terminal region) or 125I-CNBr II (NH2-terminal). Both labels were bound by the antisera. Affinity columns were prepared by binding CNBr I or CNBr II to Sepharose 4B. Antibodies specific against CNBr I or CNBr II were isolated by means of these columns, suggesting that ApoA-I had at least two antigenic sites. In other assays using labeled fragments and anti ApoA-I antisera, 125I-CNBr I was displaced by CNBr I, ApoA-I , and HDL2 but not CNBr II. Conversely, 125I-CNBr II was displaced by CNBr II, ApoA-I, and HDL2 but not by CNBr I. Thus the assays were region-specific. The reactivities of isolated ApoA-I and the ApoA-I in intact HDL2-ApoA-I) were compared in these assays. On a molar basis, HDL2-ApoA-I was consistently more reactive (2- to 5-fold) in the 125I-CNBr I than in the 125I-CNBr II assays. The findings suggest (a) that the two terminal regions of ApoA-I are immunologically distinct, (b) that the two regions can be assayed independently of each other in intact HDL2, and (c) that the COOH-terminal region is more reactive immunologically than is the NH2-terminal. The results are compatible with a more \"exposed\" position for the COOH-terminal region on the surface of HDL2.", "contents": "Structure of high density lipoprotein. The immunologic reactivities of the COOH- and NH2-terminal regions of apolipoprotein A-I. Only 5 to 10% of the apolipoprotein A-I (ApoA-I) of intact high density lipoprotein (HDL) is detectable by radioimmunoassay. In addition, when isolated ApoA-I is recombined with lipids in vitro, its immunologic reactivity is decreased by 30 to 95%. Thus, ApoA-I is less reactive immunologically in the presence of lipids. Our aim was to ascertain whether the COOH- or NH2-terminal regions of ApoA-I were equally reactive in intact HDL2. CNBr fragments of ApoA-I were produced by the method of Baker et al. (Baker, H.N., Jackson, R.L., and Gotto, A.M. (1973) Biochemistry 12, 3866-3871) and iodinated with lactoperoxidase. Double-antibody radioimmunoassays were set up using anti ApoA-I antisera and 125I-CNBr I (COOH-terminal region) or 125I-CNBr II (NH2-terminal). Both labels were bound by the antisera. Affinity columns were prepared by binding CNBr I or CNBr II to Sepharose 4B. Antibodies specific against CNBr I or CNBr II were isolated by means of these columns, suggesting that ApoA-I had at least two antigenic sites. In other assays using labeled fragments and anti ApoA-I antisera, 125I-CNBr I was displaced by CNBr I, ApoA-I , and HDL2 but not CNBr II. Conversely, 125I-CNBr II was displaced by CNBr II, ApoA-I, and HDL2 but not by CNBr I. Thus the assays were region-specific. The reactivities of isolated ApoA-I and the ApoA-I in intact HDL2-ApoA-I) were compared in these assays. On a molar basis, HDL2-ApoA-I was consistently more reactive (2- to 5-fold) in the 125I-CNBr I than in the 125I-CNBr II assays. The findings suggest (a) that the two terminal regions of ApoA-I are immunologically distinct, (b) that the two regions can be assayed independently of each other in intact HDL2, and (c) that the COOH-terminal region is more reactive immunologically than is the NH2-terminal. The results are compatible with a more \"exposed\" position for the COOH-terminal region on the surface of HDL2."} {"id": "PMID:180011", "title": "Phosphorylation of histone catalyzed by a bovine brain protein kinase.", "content": "The use of polyethyleneimine-cellulose thin layer sheets to follow the phosphorylation of histone and decomposition of ATP catalyzed by an adenosine 3':5'-monophosphate (cyclic AMP)-stimulated protein kinase, protein kinase I, has made possible a more detailed analysis of the time course of these reactions than has been achieved previously be observing only recovered phosphorylated protein. When [gamma-32P] ATP was employed, significant error was introduced by the presence of 32Pi at the solvent front on these sheets, and this limited the accuracy of the available information. However, the analysis of assays performed with [U-14C] ATP was straightforward and appeared to have an accuracy comparable to that of the present standard assay. This appears to be the first use of [U-14C] ATP to assay protein kinases. Our physical characterization of protein kinase I showed it to be a homogeneous protein species by polyacrylamide gel electrophoresis, sodium dodecyl sulfate gel electrophoresis and analytical ultracentrifugation. Kinetic studies with protein kinase I indicated the absence of histone phosphatase and cyclic AMP phosphodiesterase activity. Furthermore, the ATPase activity seen is believed to be intimately associated with the protein kinase action, particularly in view of the observed dependence of the rate of Pi production on the presence of cyclic AMP. The kinetic data for the phosphorylation of histone catalyzed by protein kinase I under full stimulation by cyclic AMP are consistent with a double displacement mechanism.", "contents": "Phosphorylation of histone catalyzed by a bovine brain protein kinase. The use of polyethyleneimine-cellulose thin layer sheets to follow the phosphorylation of histone and decomposition of ATP catalyzed by an adenosine 3':5'-monophosphate (cyclic AMP)-stimulated protein kinase, protein kinase I, has made possible a more detailed analysis of the time course of these reactions than has been achieved previously be observing only recovered phosphorylated protein. When [gamma-32P] ATP was employed, significant error was introduced by the presence of 32Pi at the solvent front on these sheets, and this limited the accuracy of the available information. However, the analysis of assays performed with [U-14C] ATP was straightforward and appeared to have an accuracy comparable to that of the present standard assay. This appears to be the first use of [U-14C] ATP to assay protein kinases. Our physical characterization of protein kinase I showed it to be a homogeneous protein species by polyacrylamide gel electrophoresis, sodium dodecyl sulfate gel electrophoresis and analytical ultracentrifugation. Kinetic studies with protein kinase I indicated the absence of histone phosphatase and cyclic AMP phosphodiesterase activity. Furthermore, the ATPase activity seen is believed to be intimately associated with the protein kinase action, particularly in view of the observed dependence of the rate of Pi production on the presence of cyclic AMP. The kinetic data for the phosphorylation of histone catalyzed by protein kinase I under full stimulation by cyclic AMP are consistent with a double displacement mechanism."} {"id": "PMID:180012", "title": "The molar ratio of the two major polypeptide components of human high density lipoprotein.", "content": "Human high density lipoprotein (HDL) and its subfractions (HDL2 and HDL3) were separated by ultracentrifugation and the molar ratio of the two major polypeptide chains apo-Gln-I and apo-Gln-II was determined by fluorescence tagging of sodium dodecyl sulfate-denatured proteins combined with polyacrylamide disc gel electrophoresis. Using purified apo-Gln-I and apo-Gln-II standards, it was found that holo HDL, holo HDL2, and holo HDL3 from all plasma samples contained a molar ratio of apo-Gln-I to the disulfide-bound dimer of apo-Gln-II of 2:1, that is a 1:1 ratio in terms of each species of polypeptide chain. The method described is useful for making repeated and rapid measurements on microgram quantities of intact lipoproteins.", "contents": "The molar ratio of the two major polypeptide components of human high density lipoprotein. Human high density lipoprotein (HDL) and its subfractions (HDL2 and HDL3) were separated by ultracentrifugation and the molar ratio of the two major polypeptide chains apo-Gln-I and apo-Gln-II was determined by fluorescence tagging of sodium dodecyl sulfate-denatured proteins combined with polyacrylamide disc gel electrophoresis. Using purified apo-Gln-I and apo-Gln-II standards, it was found that holo HDL, holo HDL2, and holo HDL3 from all plasma samples contained a molar ratio of apo-Gln-I to the disulfide-bound dimer of apo-Gln-II of 2:1, that is a 1:1 ratio in terms of each species of polypeptide chain. The method described is useful for making repeated and rapid measurements on microgram quantities of intact lipoproteins."} {"id": "PMID:180013", "title": "The structure of Paracoccus denitrificans cytochrome c550.", "content": "The crystal structure of Paracoccus (formerly Micrococcus) denitrificans cytochrome c550 has been solved by x-ray diffraction to a resolution of 2.45 A. In both amino acid sequence and molecular structure it is evolutionarily homologous with mitochondrial cytochrome c from eukaryotes and photosynthetic cytochrome c2 from purple non-sulfur bacteria. All of these cytochromes c have the same basic folding pattern, with surface insertions of extra amino acids in c550. Various strains of c2 have all, some, or none of the extra insertions observed in c550. The hydrophobic heme environment, position of aromatic rings, and structure and environment of the heme crevice, are virtually identical in cytochromes c55o, c, and c2. Radical changes observed at all regions on the molecular surface except the heme crevice argue for the importance of the crevice and the exposed edge of the heme in the transfer of electrons to and from the cytochrome molecule.", "contents": "The structure of Paracoccus denitrificans cytochrome c550. The crystal structure of Paracoccus (formerly Micrococcus) denitrificans cytochrome c550 has been solved by x-ray diffraction to a resolution of 2.45 A. In both amino acid sequence and molecular structure it is evolutionarily homologous with mitochondrial cytochrome c from eukaryotes and photosynthetic cytochrome c2 from purple non-sulfur bacteria. All of these cytochromes c have the same basic folding pattern, with surface insertions of extra amino acids in c550. Various strains of c2 have all, some, or none of the extra insertions observed in c550. The hydrophobic heme environment, position of aromatic rings, and structure and environment of the heme crevice, are virtually identical in cytochromes c55o, c, and c2. Radical changes observed at all regions on the molecular surface except the heme crevice argue for the importance of the crevice and the exposed edge of the heme in the transfer of electrons to and from the cytochrome molecule."} {"id": "PMID:180014", "title": "Sex-specific occurrence of androgen receptors in rat brain.", "content": "The metabolism and binding of [1, 2, 6, 7-3H] testosterone in male and female rat brain has been studied in an attempt to find an explanation for the relative androgen unresponsiveness characterizing the female hypothalamo-pituitary axis involved in regulation of hepatic steroid metabolism. The most significant sex differences in the pattern of [3H] testosterone metabolites recovered from several brain regions (including pituitary, pineal gland, and hypothalamus) after intraperitoneal administration of [3H] testosterone were the predominance of testosterone and androstenedione in male brain compared to the quantitative importance of 5alpha-androstane-3alpha, 17beta-diol, 5alpha-androstane-3beta, 17beta-diol, epitestosterone, and dihydroepitestosterone in female brain. One possible explanation for the androgen unresponsiveness of female rats is, therefore, the faster metabolism of testosterone to inactive compounds in female brain. Experiments both in vivo and in vitro showed the presence of high affinity, low capacity binding sites for [3H] testosterone in male pituitary, pineal gland, and hypothalamus (Kd values in the region of 1 X 10(-10) to 1 X 10(-9) M and number of binding sites 1.0 to 1.4 X 10(-14) mol per mg of protein). The steroid - macromolecular complexes generally had a pI of 5.1, were excluded from Sephadex G-200, were heat-labile, and were sensitive to protease. Competition experiments indicated the following order of ligand affinities: testosterone is greater than 5alpha-dihydrotestosterone and estradiol is greater than androstenedione is greater than corticosterone. No steroid-binding proteins of similar nature were found in pituitary, pineal gland, or hypothalamus from female rats. On the basis of these results it is suggested that the androgen unresponsiveness of female rats referred to above relates to the absence of receptor protein for androgens in female rat brain. In support of this hypothesis, 28-day-old female rats, which are known to be affected by androgens with regard to liver enzyme activities, were shown to contain receptor proteins for androgen in the brain. In conclusion, the relative androgen unresponsiveness of the female hypothalamo-pituitary axis is probably explained by the absence of receptor proteins for androgen in female hypothalamus and pituitary. The fast metabolism of testosterone in female rat brain also serves to decrease the availability of active androgen to potential receptor sites. It may be speculated that the presence of androgen receptors in male brain is the result of neonatal programming (\"imprinting\") by testicular androgen.", "contents": "Sex-specific occurrence of androgen receptors in rat brain. The metabolism and binding of [1, 2, 6, 7-3H] testosterone in male and female rat brain has been studied in an attempt to find an explanation for the relative androgen unresponsiveness characterizing the female hypothalamo-pituitary axis involved in regulation of hepatic steroid metabolism. The most significant sex differences in the pattern of [3H] testosterone metabolites recovered from several brain regions (including pituitary, pineal gland, and hypothalamus) after intraperitoneal administration of [3H] testosterone were the predominance of testosterone and androstenedione in male brain compared to the quantitative importance of 5alpha-androstane-3alpha, 17beta-diol, 5alpha-androstane-3beta, 17beta-diol, epitestosterone, and dihydroepitestosterone in female brain. One possible explanation for the androgen unresponsiveness of female rats is, therefore, the faster metabolism of testosterone to inactive compounds in female brain. Experiments both in vivo and in vitro showed the presence of high affinity, low capacity binding sites for [3H] testosterone in male pituitary, pineal gland, and hypothalamus (Kd values in the region of 1 X 10(-10) to 1 X 10(-9) M and number of binding sites 1.0 to 1.4 X 10(-14) mol per mg of protein). The steroid - macromolecular complexes generally had a pI of 5.1, were excluded from Sephadex G-200, were heat-labile, and were sensitive to protease. Competition experiments indicated the following order of ligand affinities: testosterone is greater than 5alpha-dihydrotestosterone and estradiol is greater than androstenedione is greater than corticosterone. No steroid-binding proteins of similar nature were found in pituitary, pineal gland, or hypothalamus from female rats. On the basis of these results it is suggested that the androgen unresponsiveness of female rats referred to above relates to the absence of receptor protein for androgens in female rat brain. In support of this hypothesis, 28-day-old female rats, which are known to be affected by androgens with regard to liver enzyme activities, were shown to contain receptor proteins for androgen in the brain. In conclusion, the relative androgen unresponsiveness of the female hypothalamo-pituitary axis is probably explained by the absence of receptor proteins for androgen in female hypothalamus and pituitary. The fast metabolism of testosterone in female rat brain also serves to decrease the availability of active androgen to potential receptor sites. It may be speculated that the presence of androgen receptors in male brain is the result of neonatal programming (\"imprinting\") by testicular androgen."} {"id": "PMID:180015", "title": "Biosynthesis of adrenocorticotropic hormone in mouse pituitary tumor cells.", "content": "A double antibody immunoprecipitation technique using affinity-purified adrenocorticotropic hormone (ACTH) antiserum was employed to investigate the biosynthesis of ACTH in a mouse pituitary tumor cell line. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell extracts resolved four forms of ACTH with apparent molecular weights of 4,500, 13,000, 23,000, and 31,000. These four forms of ACTH can be detected by radioimmunoassay of cell extracts or by immunoprecipitation of cell extracts following incubation of cultures in [3H] tryptophan, [3H] lysine, or [3H] tyrosine. The double antibody immunoprecipitation scheme developed is specific, quantitative, and reproducible. ACTH biosynthesis was examined in both steady and pulse-labeling experiments using [8H] tyrosine or [3H] lysine. The results of these experiments are consistent with the proposal that Mr=31,000 ACTH is the biosynthetic precursor for all three smaller forms of ACTH and that Mr=23,000 ACTH is a biosynthetic intermediate. Both Mr=13,000 ACTH and Mr=4,500 ACTH are derived from the intracellular processing of Mr=31,000 ACTH.", "contents": "Biosynthesis of adrenocorticotropic hormone in mouse pituitary tumor cells. A double antibody immunoprecipitation technique using affinity-purified adrenocorticotropic hormone (ACTH) antiserum was employed to investigate the biosynthesis of ACTH in a mouse pituitary tumor cell line. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell extracts resolved four forms of ACTH with apparent molecular weights of 4,500, 13,000, 23,000, and 31,000. These four forms of ACTH can be detected by radioimmunoassay of cell extracts or by immunoprecipitation of cell extracts following incubation of cultures in [3H] tryptophan, [3H] lysine, or [3H] tyrosine. The double antibody immunoprecipitation scheme developed is specific, quantitative, and reproducible. ACTH biosynthesis was examined in both steady and pulse-labeling experiments using [8H] tyrosine or [3H] lysine. The results of these experiments are consistent with the proposal that Mr=31,000 ACTH is the biosynthetic precursor for all three smaller forms of ACTH and that Mr=23,000 ACTH is a biosynthetic intermediate. Both Mr=13,000 ACTH and Mr=4,500 ACTH are derived from the intracellular processing of Mr=31,000 ACTH."} {"id": "PMID:180016", "title": "High molecular weight forms of adrenocorticotropic hormone are glycoproteins.", "content": "Mouse pituitary tumor cells (AtT-20/D-16v) were incubated in medium containing [3H] glucosamine or [3H] mannose. By analyzing immunoprecipitates of cell extracts and culture medium it was shown that [3H] glucosamine and [3H] mannose were incorporated into all three high molecular weight forms of ACTH; label was not incorporated into Mr=4,500 ACTH (which is thought to be similar to the 39 amino acid polypeptide form of ACTH, alpha(1-39)). Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis the apparent molecular weights of these glycoprotein forms of ACTH were 31,000, 23,000, and 13,000. Gel filtration in 6 M guanidine HCl indicated that the molecular weights of these forms of ACTH were substantially lower; sodium dodecyl sulfate-polyacrylamide gel electrophoresis has often been found to overestimate the molecular weight of glycoproteins. A significant fraction of the high molecular weight ACTH in tumor cell extracts binds to columns of concanavalin A-agarose and can be eluted with 0.2 M alpha-methyl-D-mannopyranoside; porcine alpha(1-39) does not bind to concanavalin A-agarose. High molecular weight glycoprotein ACTH can be detected in extracts of mouse and bovine pituitary by using concavalin A affinity chromatography.", "contents": "High molecular weight forms of adrenocorticotropic hormone are glycoproteins. Mouse pituitary tumor cells (AtT-20/D-16v) were incubated in medium containing [3H] glucosamine or [3H] mannose. By analyzing immunoprecipitates of cell extracts and culture medium it was shown that [3H] glucosamine and [3H] mannose were incorporated into all three high molecular weight forms of ACTH; label was not incorporated into Mr=4,500 ACTH (which is thought to be similar to the 39 amino acid polypeptide form of ACTH, alpha(1-39)). Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis the apparent molecular weights of these glycoprotein forms of ACTH were 31,000, 23,000, and 13,000. Gel filtration in 6 M guanidine HCl indicated that the molecular weights of these forms of ACTH were substantially lower; sodium dodecyl sulfate-polyacrylamide gel electrophoresis has often been found to overestimate the molecular weight of glycoproteins. A significant fraction of the high molecular weight ACTH in tumor cell extracts binds to columns of concanavalin A-agarose and can be eluted with 0.2 M alpha-methyl-D-mannopyranoside; porcine alpha(1-39) does not bind to concanavalin A-agarose. High molecular weight glycoprotein ACTH can be detected in extracts of mouse and bovine pituitary by using concavalin A affinity chromatography."} {"id": "PMID:180017", "title": "A relation between (NAD+)/(NADH) potentials and glucose utilization in rat brain slices.", "content": "Changes in several parameters involved in the control of metabolism were correlated with changes in glucose utilization in rat brain slices incubated under conditions which reduced glucose oxidation by 40 to 70%. The parameters included: the concentrations of ATP, ADP, AMP, and the adenylate energy charge; the cytoplasmic oxidation-reduction state ([NAD+]/[NADH]), determined from the [pyruvate]/[lactate] equilibrium; the mitochondrial oxidation-reduction state, determined from the [NH4+] ]2-oxoglutarate]/[glutamate] Equilibrium; the cytoplasmic and mitochondrial oxidation-reduction potentials (in volts), calculated from the respective [NAD+]/ [NADH] ratios using the Nernst equation; and the difference between the cytoplasmic and mitochondrial [NAD+]/[NADH] potentials. The conversion of [3, 4-14C] glucose to 14CO2 and of [U-14C] glucose to acetylcholine and to lipids, proteins, and nucleic acids by the brain slices were also determined. The values obtained by subtracting the mitochondrial from the cytoplasmic [NAD+1/[NADH] potentials correlated more closely with glucose utilization than did other parameters, under the conditions studied. For the synthesis of acetylcholine, the correlation coefficient was 0.96, and for the production of 14CO2 from [3, 4-14C] glucose it was 0.82.", "contents": "A relation between (NAD+)/(NADH) potentials and glucose utilization in rat brain slices. Changes in several parameters involved in the control of metabolism were correlated with changes in glucose utilization in rat brain slices incubated under conditions which reduced glucose oxidation by 40 to 70%. The parameters included: the concentrations of ATP, ADP, AMP, and the adenylate energy charge; the cytoplasmic oxidation-reduction state ([NAD+]/[NADH]), determined from the [pyruvate]/[lactate] equilibrium; the mitochondrial oxidation-reduction state, determined from the [NH4+] ]2-oxoglutarate]/[glutamate] Equilibrium; the cytoplasmic and mitochondrial oxidation-reduction potentials (in volts), calculated from the respective [NAD+]/ [NADH] ratios using the Nernst equation; and the difference between the cytoplasmic and mitochondrial [NAD+]/[NADH] potentials. The conversion of [3, 4-14C] glucose to 14CO2 and of [U-14C] glucose to acetylcholine and to lipids, proteins, and nucleic acids by the brain slices were also determined. The values obtained by subtracting the mitochondrial from the cytoplasmic [NAD+1/[NADH] potentials correlated more closely with glucose utilization than did other parameters, under the conditions studied. For the synthesis of acetylcholine, the correlation coefficient was 0.96, and for the production of 14CO2 from [3, 4-14C] glucose it was 0.82."} {"id": "PMID:180018", "title": "Human erythrocyte pyrimidine nucleoside monophosphate kinase. Partial purification and properties of two allelic gene products.", "content": "Human pyrimidine nucleoside monophosphate kinase is a polymorphic enzyme having two allelic gene products, UMPK 1 and UMPK 2, in several populations. A procedure is described for the partial purification of this enzyme from human red blood cells resulting in a 1500-fold purification of the enzyme for UMPK 1 and 583-fold for UMPK 2. The purified enzyme preparation catalyzed the phosphorylation of UMP, CMP, and dCMP, and used ATP as the preferred phosphate donor. The heavy metals, mercury, and copper, were found to be strong inhibitors of pyrimidine nucleoside monophosphate kinase activity. EDTA was found to protect the enzyme from inactivation by the heavy metals, and 2-mercaptoethanol stabilized the enzyme during purification. UMPK 1 and UMPK 2 were found to have similar kinetic properties; however, UMPK 2 had a slower electrophoretic mobility and greater thermolability than UMPK 1.", "contents": "Human erythrocyte pyrimidine nucleoside monophosphate kinase. Partial purification and properties of two allelic gene products. Human pyrimidine nucleoside monophosphate kinase is a polymorphic enzyme having two allelic gene products, UMPK 1 and UMPK 2, in several populations. A procedure is described for the partial purification of this enzyme from human red blood cells resulting in a 1500-fold purification of the enzyme for UMPK 1 and 583-fold for UMPK 2. The purified enzyme preparation catalyzed the phosphorylation of UMP, CMP, and dCMP, and used ATP as the preferred phosphate donor. The heavy metals, mercury, and copper, were found to be strong inhibitors of pyrimidine nucleoside monophosphate kinase activity. EDTA was found to protect the enzyme from inactivation by the heavy metals, and 2-mercaptoethanol stabilized the enzyme during purification. UMPK 1 and UMPK 2 were found to have similar kinetic properties; however, UMPK 2 had a slower electrophoretic mobility and greater thermolability than UMPK 1."} {"id": "PMID:180019", "title": "Cyclic 3':5'-nucleotide phosphodiesterase. Ca2+ confers more helical conformation to the protein activator.", "content": "The ultraviolet spectrum of a protein activator of cyclic nucleotide phosphodiesterase and adenylate cyclase purified to homogeneity from bovine brain displayed absorption peaks at 252, 259, 265, 269, and 277 nm. The activator contained no phosphate and did not serve as a substrate for cyclic adenosine 3':5'-monophosphate- or cyclic guanosine 3':5'-monophosphate-dependent protein kinases. The activator binds Ca2+, and the active form appears to be a Ca2+ activator complex (Lin, Y.M., Liu, Y.P., and Cheung, W.Y. (1974) J. Biol. Chem. 249, 4943-4954). Optical rotatory dispersion measurement showed that the Ca2+-free activator exhibited a reduced mean residue rotation ([m']231) of -5700, corresponding to 39% of helical content. In the presence of Ca2+, the [m']231 was increased to -7500, corresponding to 57% of helical content. The Ca2+ -induced conformational change was corroborated by a chemical method. In the presence of Ca2+, the activator was more resistant to trypsin inactivation, presumably because proteins with more helical structures are more resistant to tryptic attack. The activator is rich in aspartate and glutamate. Chemical block of some of the carboxyl groups with glycine ethyl ester or methoxyamine diminished the [m']231 of the activator and its activity, suggesting that blockade of some of the carboxyl groups in the activator unfolded the molecule, leading to a loss of activity. We conclude that Ca2+, which confers more helical structure to the activator, converts the inactive, less helical structure to the active, more helical structure, and that chemical modification of the activator leading to unfolding of the molecule abolishes its biological activity.", "contents": "Cyclic 3':5'-nucleotide phosphodiesterase. Ca2+ confers more helical conformation to the protein activator. The ultraviolet spectrum of a protein activator of cyclic nucleotide phosphodiesterase and adenylate cyclase purified to homogeneity from bovine brain displayed absorption peaks at 252, 259, 265, 269, and 277 nm. The activator contained no phosphate and did not serve as a substrate for cyclic adenosine 3':5'-monophosphate- or cyclic guanosine 3':5'-monophosphate-dependent protein kinases. The activator binds Ca2+, and the active form appears to be a Ca2+ activator complex (Lin, Y.M., Liu, Y.P., and Cheung, W.Y. (1974) J. Biol. Chem. 249, 4943-4954). Optical rotatory dispersion measurement showed that the Ca2+-free activator exhibited a reduced mean residue rotation ([m']231) of -5700, corresponding to 39% of helical content. In the presence of Ca2+, the [m']231 was increased to -7500, corresponding to 57% of helical content. The Ca2+ -induced conformational change was corroborated by a chemical method. In the presence of Ca2+, the activator was more resistant to trypsin inactivation, presumably because proteins with more helical structures are more resistant to tryptic attack. The activator is rich in aspartate and glutamate. Chemical block of some of the carboxyl groups with glycine ethyl ester or methoxyamine diminished the [m']231 of the activator and its activity, suggesting that blockade of some of the carboxyl groups in the activator unfolded the molecule, leading to a loss of activity. We conclude that Ca2+, which confers more helical structure to the activator, converts the inactive, less helical structure to the active, more helical structure, and that chemical modification of the activator leading to unfolding of the molecule abolishes its biological activity."} {"id": "PMID:180020", "title": "Role of phospholipids in the calcium-dependent ATPase of the sarcoplasmic reticulum. Enzymatic and ESR studies with phospholipid-replaced membranes.", "content": "Three types of partially purified ATPase enzymes having different phospholipid contents and compositions have been prepared: (a) an enzyme whose phospholipid moiety has been replaced predominantly by dioleoyl lecithin (DOL-enzyme), with about the same phospholipid content as the original sarcoplasmic reticulum, (b) dipalmitoyl lecithin-replaced enzyme whose phospholipid content is 30% of that of DOL-enzyme (DPL-enzyme), and (c) a partially delipidated enzyme with about the same phospholipid content as DPL-enzyme but with the original sarcoplasmic reticulum phospholipid composition (del-enzyme). The temperature dependence of Ca2+-activated ATPase activity of these preparations showed clearcut differences; with DOL-enzyme there was no appreciable break in the Arrhenius plot in the 3-40 degrees range; DPL-enzyme showed a break at 29 degrees, and del-enzyme and sarcoplasmic reticulum one at 18 degrees. Transition temperatures obtained from ESR studies with the use of spin-labeled stearic acid incorporated into the membranes agreed with those derived from ATPase assays. Thermo-dynamic analysis of the ATP hydrolysis rates shows that DPL-enzyme has considerably larger values of activation enthalpy and activation entropy below the transition temperature (29 degrees) than those of the other preparations, while all enzyme preparations show similar free energies of activation. The ESR data show that below their transition temperatures DPL-enzyme, and to a lesser degree del-enzyme, have a strongly restricted motion of their phospholipid molecules as compared with either DOL-enzyme or sarcoplasmic reticulum. Studies on the formation and decomposition of phosphoenzyme have been carried out with the three types of ATPase preparations. At 0 degrees, the rate of inorganic phosphate liberation is 8 times lower in DPL-enzyme than in del-enzyme with little difference in the steady state level of phosphoenzyme. In DOL-enzyme, the level of phosphoenzyme and the rate of inorganic phosphate liberation are 1.8 and 3.5 times higher than the corresponding values obtained with del-enzyme. Addition of ADP to the phosphorylated intermediate of DPL-enzyme induces a fast reversal of the phosphorylation reaction. These results indicate that the physical state of the phospholipid molecules associated with the enzyme affects the decomposition of phosphoenzyme, with little effect on the phosphorylation reaction and its reversal.", "contents": "Role of phospholipids in the calcium-dependent ATPase of the sarcoplasmic reticulum. Enzymatic and ESR studies with phospholipid-replaced membranes. Three types of partially purified ATPase enzymes having different phospholipid contents and compositions have been prepared: (a) an enzyme whose phospholipid moiety has been replaced predominantly by dioleoyl lecithin (DOL-enzyme), with about the same phospholipid content as the original sarcoplasmic reticulum, (b) dipalmitoyl lecithin-replaced enzyme whose phospholipid content is 30% of that of DOL-enzyme (DPL-enzyme), and (c) a partially delipidated enzyme with about the same phospholipid content as DPL-enzyme but with the original sarcoplasmic reticulum phospholipid composition (del-enzyme). The temperature dependence of Ca2+-activated ATPase activity of these preparations showed clearcut differences; with DOL-enzyme there was no appreciable break in the Arrhenius plot in the 3-40 degrees range; DPL-enzyme showed a break at 29 degrees, and del-enzyme and sarcoplasmic reticulum one at 18 degrees. Transition temperatures obtained from ESR studies with the use of spin-labeled stearic acid incorporated into the membranes agreed with those derived from ATPase assays. Thermo-dynamic analysis of the ATP hydrolysis rates shows that DPL-enzyme has considerably larger values of activation enthalpy and activation entropy below the transition temperature (29 degrees) than those of the other preparations, while all enzyme preparations show similar free energies of activation. The ESR data show that below their transition temperatures DPL-enzyme, and to a lesser degree del-enzyme, have a strongly restricted motion of their phospholipid molecules as compared with either DOL-enzyme or sarcoplasmic reticulum. Studies on the formation and decomposition of phosphoenzyme have been carried out with the three types of ATPase preparations. At 0 degrees, the rate of inorganic phosphate liberation is 8 times lower in DPL-enzyme than in del-enzyme with little difference in the steady state level of phosphoenzyme. In DOL-enzyme, the level of phosphoenzyme and the rate of inorganic phosphate liberation are 1.8 and 3.5 times higher than the corresponding values obtained with del-enzyme. Addition of ADP to the phosphorylated intermediate of DPL-enzyme induces a fast reversal of the phosphorylation reaction. These results indicate that the physical state of the phospholipid molecules associated with the enzyme affects the decomposition of phosphoenzyme, with little effect on the phosphorylation reaction and its reversal."} {"id": "PMID:180021", "title": "Thyroid-stimulating hormone binding to beef thyroid membranes. Role of N-acetylneuraminic acid.", "content": "The effect of sugars on 125I-thyroid-stimulating hormone binding to beef thyroid membranes was studied to determine their role in thyroid-stimulating hormone (TSH) binding. At 0.1 M concentration, N-acetylneuraminic acid produced a 3- to 7-fold increase in TSH binding, was the only sugar to enhance TSH binding, and did so whether binding was determined in the cyclase medium or under conditions of optimum binding. The enhanced TSH binding remained after the membranes were removed from the high NeuAc concentration and an effect was observed at concentrations of 10 mM NeuAc. NeuAc did not alter the kinetics of TSH binding but the pH optimum for TSH binding shifted from pH 5.5 to 7.5 in the presence of NeuAc. Incubation of the membranes with increasing concentrations of NeuAc resulted in increased sialic acid content of the membranes. The NeuAc concentration curve of membrane sialic acid and TSH binding were roughly parallel. The capacity of the low affinity site increased from 0.74 to 2.5 nmol/mg of protein in the presence of NeuAc. The apparent affinity (0.88 X 10(6) M-1) of this site was unaffected by NeuAc. With the high affinity site, NeuAc increased both the apparent affinity and capacity from 2.2 X 10(8)M-1 to 5.5 X 10(8) M-1 and 1.6 to 3.1 pmol/mg of protein, respectively. Neuraminidase or neuraminidase plus beta-galactosidase incubation of the membranes removed approximately 60% of the sialic acid from the membranes within 15 to 30 min but did not affect TSH binding. Large quantities of sialic acid were detected in the soluble fractions during isolation of the membranes, 4 to 5% of which was ultrafilterable and not associated with high molecular weight proteins. It is concluded that among the sugars tested, NeuAc exhibits an unique effect on TSH binding that may have physiological significance. The inability to alter TSH binding by enzymatic removal of endogenous sialic acid suggests that either NeuAc resistant to hydrolysis is sufficient to maintain TSH binding or that NeuAc important in TSH binding is removed during membrane preparation but is replaced by incubation with exogenous NeuAc.", "contents": "Thyroid-stimulating hormone binding to beef thyroid membranes. Role of N-acetylneuraminic acid. The effect of sugars on 125I-thyroid-stimulating hormone binding to beef thyroid membranes was studied to determine their role in thyroid-stimulating hormone (TSH) binding. At 0.1 M concentration, N-acetylneuraminic acid produced a 3- to 7-fold increase in TSH binding, was the only sugar to enhance TSH binding, and did so whether binding was determined in the cyclase medium or under conditions of optimum binding. The enhanced TSH binding remained after the membranes were removed from the high NeuAc concentration and an effect was observed at concentrations of 10 mM NeuAc. NeuAc did not alter the kinetics of TSH binding but the pH optimum for TSH binding shifted from pH 5.5 to 7.5 in the presence of NeuAc. Incubation of the membranes with increasing concentrations of NeuAc resulted in increased sialic acid content of the membranes. The NeuAc concentration curve of membrane sialic acid and TSH binding were roughly parallel. The capacity of the low affinity site increased from 0.74 to 2.5 nmol/mg of protein in the presence of NeuAc. The apparent affinity (0.88 X 10(6) M-1) of this site was unaffected by NeuAc. With the high affinity site, NeuAc increased both the apparent affinity and capacity from 2.2 X 10(8)M-1 to 5.5 X 10(8) M-1 and 1.6 to 3.1 pmol/mg of protein, respectively. Neuraminidase or neuraminidase plus beta-galactosidase incubation of the membranes removed approximately 60% of the sialic acid from the membranes within 15 to 30 min but did not affect TSH binding. Large quantities of sialic acid were detected in the soluble fractions during isolation of the membranes, 4 to 5% of which was ultrafilterable and not associated with high molecular weight proteins. It is concluded that among the sugars tested, NeuAc exhibits an unique effect on TSH binding that may have physiological significance. The inability to alter TSH binding by enzymatic removal of endogenous sialic acid suggests that either NeuAc resistant to hydrolysis is sufficient to maintain TSH binding or that NeuAc important in TSH binding is removed during membrane preparation but is replaced by incubation with exogenous NeuAc."} {"id": "PMID:180022", "title": "Isolation of stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian heart devoid of inhibitory modulator of adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "The stimulatory and inhibitory activities in the crude preparation of protein kinase modulator from dog heart were separated by Sephadex G-100 gel filtration, and the stimulatory modulator was further purified by DEAE-cellulose chromatography. The isolated stimulatory modulator, as the crude modulator preparation, stimulated the activity of the purified guanosine 3':5'-monophosphate (cGMP)-dependent protein kinases of both mammalian and arthropod origins in the presence of cGMP. The cGMP-dependent protein kinases were not activated by cGMP in the absence of either the isolated stimulatory modulator or the crude modulator. The stimulatory modulator, unlike the crude modulator had no effect on the activity of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase. The stimulatory modulator was a protein since its activity was destroyed by trypsin but was resistant to hydrolysis by DNase, RNase, phospholipase C, and lysozyme. The isolated inhibitory modulator, presumably the same as the protein inhibitor of cAMP-dependent protein kinase reported by Walsh et al. (Wash. D.A., Ashby, C.D., Gonzalez, C., Calkins, D., Fischer. E.H., and Krebs, E.G. (1971) J. Biol. Chem. 246, 1977-1985), depressed the cAMP-stimulated activity of cAMP-dependent protein kinase as did the crude preparation of protein kinase modulator. The isolated inhibitory modulator, unlike the crude preparation, was without effect on cGMP-dependent protein kinase. The present findings provide evidence to support that in mammals there are separate proteins for the stimulatory and the inhibitory activities of protein kinase modulator, in contrast to the modulator from an arthropod tissue (lobster tail muscle, Donnelly et al. (Donnelly, T.E., Jr., Kuo, J.F., Reyes, P.L., Liu, Y.P., and Greengard, P. (1973) J. Biol. Chem. 248, 190-198) which has been shown to possess both activities.", "contents": "Isolation of stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian heart devoid of inhibitory modulator of adenosine 3':5'-monophosphate-dependent protein kinase. The stimulatory and inhibitory activities in the crude preparation of protein kinase modulator from dog heart were separated by Sephadex G-100 gel filtration, and the stimulatory modulator was further purified by DEAE-cellulose chromatography. The isolated stimulatory modulator, as the crude modulator preparation, stimulated the activity of the purified guanosine 3':5'-monophosphate (cGMP)-dependent protein kinases of both mammalian and arthropod origins in the presence of cGMP. The cGMP-dependent protein kinases were not activated by cGMP in the absence of either the isolated stimulatory modulator or the crude modulator. The stimulatory modulator, unlike the crude modulator had no effect on the activity of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase. The stimulatory modulator was a protein since its activity was destroyed by trypsin but was resistant to hydrolysis by DNase, RNase, phospholipase C, and lysozyme. The isolated inhibitory modulator, presumably the same as the protein inhibitor of cAMP-dependent protein kinase reported by Walsh et al. (Wash. D.A., Ashby, C.D., Gonzalez, C., Calkins, D., Fischer. E.H., and Krebs, E.G. (1971) J. Biol. Chem. 246, 1977-1985), depressed the cAMP-stimulated activity of cAMP-dependent protein kinase as did the crude preparation of protein kinase modulator. The isolated inhibitory modulator, unlike the crude preparation, was without effect on cGMP-dependent protein kinase. The present findings provide evidence to support that in mammals there are separate proteins for the stimulatory and the inhibitory activities of protein kinase modulator, in contrast to the modulator from an arthropod tissue (lobster tail muscle, Donnelly et al. (Donnelly, T.E., Jr., Kuo, J.F., Reyes, P.L., Liu, Y.P., and Greengard, P. (1973) J. Biol. Chem. 248, 190-198) which has been shown to possess both activities."} {"id": "PMID:180023", "title": "Function and structure of RNA polymerase from vesicular stomatitis virus.", "content": "The RNA-dependent RNA polymerase associated with vesicular stomatitis virus was isolated to apparent homogeneity by a newly developed procedure, which includes stepwise removal of proteins from virions by successive treatment with high concentrations of cesium sulfate and cesium chloride, followed by glycerol gradient centrifugation or chromatography on phosphocellulose or DEAE-Sephadex column. The polymerase thus purified contained L (large protein) and NS proteins as the intrinsic subunits and multiple species of enzyme were found which differ in the molar ratio of L to NS. Since the enzyme with the highest activity was composed of equimolar amounts of the two subunits and exhibited the sedimentation coefficient of approximately 11 S in a buffer containing 0.2 M NaCl, the structure of active protomer was suggested to be (L)1(NS)1. In accordance with this conclusion, enzyme preparations deficient in the content of NS protein, were activated by the addition of preparations deficient in the content of NS protein. The purified RNA polymerase catalyzed the synthesis of poly(A), which was covalently attached to the 3' termini of RNA products, and RNA, only in the presence of all 4 substrates. The present finding might be the first which indicates that the transcriptase itself catalyzes post-transcriptional modification of mRNA by adding poly(A) sequences to the 3'-OH termini. The molecular mechanism of the switch from transcription to poly(A) synthesis, however, remains to be investigated.", "contents": "Function and structure of RNA polymerase from vesicular stomatitis virus. The RNA-dependent RNA polymerase associated with vesicular stomatitis virus was isolated to apparent homogeneity by a newly developed procedure, which includes stepwise removal of proteins from virions by successive treatment with high concentrations of cesium sulfate and cesium chloride, followed by glycerol gradient centrifugation or chromatography on phosphocellulose or DEAE-Sephadex column. The polymerase thus purified contained L (large protein) and NS proteins as the intrinsic subunits and multiple species of enzyme were found which differ in the molar ratio of L to NS. Since the enzyme with the highest activity was composed of equimolar amounts of the two subunits and exhibited the sedimentation coefficient of approximately 11 S in a buffer containing 0.2 M NaCl, the structure of active protomer was suggested to be (L)1(NS)1. In accordance with this conclusion, enzyme preparations deficient in the content of NS protein, were activated by the addition of preparations deficient in the content of NS protein. The purified RNA polymerase catalyzed the synthesis of poly(A), which was covalently attached to the 3' termini of RNA products, and RNA, only in the presence of all 4 substrates. The present finding might be the first which indicates that the transcriptase itself catalyzes post-transcriptional modification of mRNA by adding poly(A) sequences to the 3'-OH termini. The molecular mechanism of the switch from transcription to poly(A) synthesis, however, remains to be investigated."} {"id": "PMID:180024", "title": "Size-dependent allosteric effects of monovalent cations on rabbit liver fructose-1,6-bisphosphatase.", "content": "Effects of monovalent cations on the neutral rabbit liver fructose-1,6-bisphosphatase are multifunctional and dependent on their nonhydrated ionic size. (a) The maximal velocity is increased by addition of monovalent cations with the optimum stimulation occurring with a nonhydrated ionic radius of 1.2 A in the presence of a chelating agent such as EDTA. (B) Activation curves are sigmoidal with n values varying from 1.5 to 2.3 as ionic radius of monovalent cation increases. The apparent Ka values from 16.0 to 180 mM, obtained for various monovalent cations, have a linear relationship to ionic radii of cations. (c) At lower concentrations of fructose 1,6-bisphosphate monovalent cations show the inhibitory effect and the apparent Km for fructose 1,6-bisphosphate is increased as the concentration of monovalent cation is increased. A linear relationship is obtained between the slopes of increase in the Km and the reciprocals of ionic volume of monovalent cations. (d) The apparent Ka for Mg2+ is also increased as the concentration of monovalent cation is increased, and a linear relationship is obtained again between the increases in Ka and the reciprocals of ionic volume of monovalent cations. The cooperative nature for Mg2+ saturation is decreased as the Ka increases. (e) The apparent Ki for AMP is also linearly altered as the concentration of monovalent cation is varied. However, the alteration of the Ki is unusual, that is, the smaller cations than K+ increase the Ki (Li+ greater than Na+ greater than NH4+), whereas the larger cations decrease the value ((CH2CH2OH)3N+ greater than Cs+ greater than Rb+). The effect of K+ is insignificant. Alterations in the Ki are also linearly related to the reciprocals of ionic volume of monovalent cations. The cooperative nature for AMP inhibition is decreased or increased as the Ki increased or decreased. (f) In the absence of the chelating agent, the curves for Mg2+ saturation and AMP inhibition were hyperbolic without monovalent cations. By addition of monovalent cation the Ka for Mg+2+ or Ki for AMP is increased and cooperative natures for binding of both ligands are induced. For nonspherical monovalent cations, the application of \"functional ionic radius\" is proposed. Functional ionic radii of NH4+, (CH2OH)3CNH3+, and (CH2CH2OH)3N+ are estimated to be 1.17, 2.55, and 2.87 A, respectively. The presence of two distinct sites for the actions of monovalent cations is suggested.", "contents": "Size-dependent allosteric effects of monovalent cations on rabbit liver fructose-1,6-bisphosphatase. Effects of monovalent cations on the neutral rabbit liver fructose-1,6-bisphosphatase are multifunctional and dependent on their nonhydrated ionic size. (a) The maximal velocity is increased by addition of monovalent cations with the optimum stimulation occurring with a nonhydrated ionic radius of 1.2 A in the presence of a chelating agent such as EDTA. (B) Activation curves are sigmoidal with n values varying from 1.5 to 2.3 as ionic radius of monovalent cation increases. The apparent Ka values from 16.0 to 180 mM, obtained for various monovalent cations, have a linear relationship to ionic radii of cations. (c) At lower concentrations of fructose 1,6-bisphosphate monovalent cations show the inhibitory effect and the apparent Km for fructose 1,6-bisphosphate is increased as the concentration of monovalent cation is increased. A linear relationship is obtained between the slopes of increase in the Km and the reciprocals of ionic volume of monovalent cations. (d) The apparent Ka for Mg2+ is also increased as the concentration of monovalent cation is increased, and a linear relationship is obtained again between the increases in Ka and the reciprocals of ionic volume of monovalent cations. The cooperative nature for Mg2+ saturation is decreased as the Ka increases. (e) The apparent Ki for AMP is also linearly altered as the concentration of monovalent cation is varied. However, the alteration of the Ki is unusual, that is, the smaller cations than K+ increase the Ki (Li+ greater than Na+ greater than NH4+), whereas the larger cations decrease the value ((CH2CH2OH)3N+ greater than Cs+ greater than Rb+). The effect of K+ is insignificant. Alterations in the Ki are also linearly related to the reciprocals of ionic volume of monovalent cations. The cooperative nature for AMP inhibition is decreased or increased as the Ki increased or decreased. (f) In the absence of the chelating agent, the curves for Mg2+ saturation and AMP inhibition were hyperbolic without monovalent cations. By addition of monovalent cation the Ka for Mg+2+ or Ki for AMP is increased and cooperative natures for binding of both ligands are induced. For nonspherical monovalent cations, the application of \"functional ionic radius\" is proposed. Functional ionic radii of NH4+, (CH2OH)3CNH3+, and (CH2CH2OH)3N+ are estimated to be 1.17, 2.55, and 2.87 A, respectively. The presence of two distinct sites for the actions of monovalent cations is suggested."} {"id": "PMID:180025", "title": "Kinetic resolution of ligand binding to the alpha and beta chains within human hemoglobin.", "content": "Nitric oxide has been used as a chain-specific, spin label of unliganded heme groups present in kinetic mixtures of human hemoglobin and n-butyl isocyanide. In these experiments, deoxyhemoglobin was reacted with n-butyl isocyanide for a controlled time and then mixed rapidly with a high concentration of nitric oxide to fill residual, unoccupied heme sites. The final mixture was frozen immediately after formation to prevent any displacement of bound isonitrile. The EPR spectrum of the frozen sample was resolved into alpha and beta nitric oxide components; these reflect the relative proportions of alpha- and beta-heme sites which were unoccupied by n-butyl isocyanide. Individual time courses for the alpha and beta subunits were obtained by varying the time between the formation of the isonitrile/hemoglobin mixture and its reaction with nitric oxide. At pH 7.0 only the beta chain time course exhibits an initial rapid phase; the alpha chain time course is monophasic, exhibiting almost, exponential behavior. This result shows unequivocally that the beta-hemes within deoxyhemoglobin react much more rapidly with n-butyl isocyanide than the alpha hemes.", "contents": "Kinetic resolution of ligand binding to the alpha and beta chains within human hemoglobin. Nitric oxide has been used as a chain-specific, spin label of unliganded heme groups present in kinetic mixtures of human hemoglobin and n-butyl isocyanide. In these experiments, deoxyhemoglobin was reacted with n-butyl isocyanide for a controlled time and then mixed rapidly with a high concentration of nitric oxide to fill residual, unoccupied heme sites. The final mixture was frozen immediately after formation to prevent any displacement of bound isonitrile. The EPR spectrum of the frozen sample was resolved into alpha and beta nitric oxide components; these reflect the relative proportions of alpha- and beta-heme sites which were unoccupied by n-butyl isocyanide. Individual time courses for the alpha and beta subunits were obtained by varying the time between the formation of the isonitrile/hemoglobin mixture and its reaction with nitric oxide. At pH 7.0 only the beta chain time course exhibits an initial rapid phase; the alpha chain time course is monophasic, exhibiting almost, exponential behavior. This result shows unequivocally that the beta-hemes within deoxyhemoglobin react much more rapidly with n-butyl isocyanide than the alpha hemes."} {"id": "PMID:180026", "title": "Stimulation of ornithine decarboxylase synthesis and its control by polyamines in regenerating rat liver and cultured rat hepatoma cells.", "content": "Ornithine decarboxylase has been induced in log phase hepatoma cells grown in suspension culture. Induction with N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate produced a 4-fold increase in enzyme activity by 3 hours which was followed by a return to base levels by 6 hours. Induction with dexamethasone, a potent synthetic glucocorticoid, exhibited a slow steady rate of increase in enzyme activity, reaching a plateau level of approximately 5- to 6-fold stimulation by about 12 hours. Induced cell and regenerating rat liver ornithine decarboxylase were shown to be indistinguishable by titration with antibody monospecific to the latter and by heat stability. L-[14C]Leucine incorporation into immunoprecipitable enzyme protein after induction in vitro or partial hepatectomy showed an increase which, when coupled with the increase in enzymatic activity, indicated de novo synthesis of enzyme protein. Physiological concentrations of the naturally occurring polyamines, spermidine and spermine, abolish cyclic AMP induction whereas they have no effect on dexamethasone induction. Both inductions were abolished by cycloheximide; in contrast, inhibition by actinomycin D was complete for dexamethasone induction and only partial with respect to cyclic AMP induction. The different time pattern of induction seen with cyclic AMP and dexamethasone, the partial inhibition of the cyclic AMP induction seen with actinomycin D, as well as the absence of inhibition of the dexamethasone induction by polyamines, indicate that these inducers might affect different aspects of the control of the same enzyme.", "contents": "Stimulation of ornithine decarboxylase synthesis and its control by polyamines in regenerating rat liver and cultured rat hepatoma cells. Ornithine decarboxylase has been induced in log phase hepatoma cells grown in suspension culture. Induction with N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate produced a 4-fold increase in enzyme activity by 3 hours which was followed by a return to base levels by 6 hours. Induction with dexamethasone, a potent synthetic glucocorticoid, exhibited a slow steady rate of increase in enzyme activity, reaching a plateau level of approximately 5- to 6-fold stimulation by about 12 hours. Induced cell and regenerating rat liver ornithine decarboxylase were shown to be indistinguishable by titration with antibody monospecific to the latter and by heat stability. L-[14C]Leucine incorporation into immunoprecipitable enzyme protein after induction in vitro or partial hepatectomy showed an increase which, when coupled with the increase in enzymatic activity, indicated de novo synthesis of enzyme protein. Physiological concentrations of the naturally occurring polyamines, spermidine and spermine, abolish cyclic AMP induction whereas they have no effect on dexamethasone induction. Both inductions were abolished by cycloheximide; in contrast, inhibition by actinomycin D was complete for dexamethasone induction and only partial with respect to cyclic AMP induction. The different time pattern of induction seen with cyclic AMP and dexamethasone, the partial inhibition of the cyclic AMP induction seen with actinomycin D, as well as the absence of inhibition of the dexamethasone induction by polyamines, indicate that these inducers might affect different aspects of the control of the same enzyme."} {"id": "PMID:180027", "title": "Enzymological studies on hereditary avian muscular dystrophy.", "content": "White and red muscles of normal and genetically dystrophic chickens were compared with regards to activity levels of three soluble enzymes, glyceraldehyde-3-phosphate dehydrogenase, creatine phosphokinase, and acetyl phosphatase. In dystrophic white muscle (pectoral), activity of the two sulfhydryl enzymes, glyceraldehyde-3-phosphate dehydrogenase and creatine phosphokinase, was preferentially lost from the sarcoplasm resulting in decreased specific activities. By contrast, acetyl phosphatase was preferentially retained and showed increased specific activity. Dystrophic white muscle had decreased sulfhydryl content in the soluble proteins, severe reduction in muscle mass, fatty infiltration, and fragmentation of fibers. Red dystrophic muscles (thigh) were minimally involved in accordance with the known sparing of red fibers. Enzyme activities were correlated with histological observations. The results suggested that the disease process in dystrophic white muscle may be related to alterations in the sulfhydryl groups of proteins. The data are correlated with the beneficial effects of our treatment of hereditary avian dystrophy with the sulfhydryl compound, penicillamine (Chou, T.H., Hill, E.J., Bartle, E., Woolley, K., LeQuire, V., Olson, W., Roelofs, R., and Park, J.H. (1975) J. Clin. Invest. 56, 842-849).", "contents": "Enzymological studies on hereditary avian muscular dystrophy. White and red muscles of normal and genetically dystrophic chickens were compared with regards to activity levels of three soluble enzymes, glyceraldehyde-3-phosphate dehydrogenase, creatine phosphokinase, and acetyl phosphatase. In dystrophic white muscle (pectoral), activity of the two sulfhydryl enzymes, glyceraldehyde-3-phosphate dehydrogenase and creatine phosphokinase, was preferentially lost from the sarcoplasm resulting in decreased specific activities. By contrast, acetyl phosphatase was preferentially retained and showed increased specific activity. Dystrophic white muscle had decreased sulfhydryl content in the soluble proteins, severe reduction in muscle mass, fatty infiltration, and fragmentation of fibers. Red dystrophic muscles (thigh) were minimally involved in accordance with the known sparing of red fibers. Enzyme activities were correlated with histological observations. The results suggested that the disease process in dystrophic white muscle may be related to alterations in the sulfhydryl groups of proteins. The data are correlated with the beneficial effects of our treatment of hereditary avian dystrophy with the sulfhydryl compound, penicillamine (Chou, T.H., Hill, E.J., Bartle, E., Woolley, K., LeQuire, V., Olson, W., Roelofs, R., and Park, J.H. (1975) J. Clin. Invest. 56, 842-849)."} {"id": "PMID:180028", "title": "Guanosine 3':5'-monophosphate-dependent protein kinase from silkworm, properties of a catalytic fragment obtained by limited proteolysis.", "content": "Although guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) which was partially purified from silkworm pupae was not dissociated by cyclic GMP into catalytic and regulatory subunits as described for adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) (Takai, Y., Nakaya, S., Inoue, M., Kishimoto, A., Nishiyama, K., Yamamura, H., and Nishizuka, Y. (1976) J. Biol. Chem. 251, 1481-1487), limited proteolysis with trypsin resulted in the formation of catalytic and cyclic GMP-binding fragments which showed molecular weights of approximately 3.4 X 10(4) and 3.6 X 10(4), respectively (the molecular weight of native protein kinase G was 1.4 X 10(5)). The catalytic fragment did not bind cyclic GMP and was fully active in the absence of the cyclic nucleotide. The fragment did not show an absolute requirement for a sulfhydryl compound and high concentrations of Mg2+ (50 to 100 mM), both of which were necessary for the maximal activation of native protein kinase G. The catalytic fragment was not inhibited by the cyclic GMP-binding fragment nor by the regulatory subunit of protein kinase A. Inversely, the cyclic GMP-binding fragment was unable to inhibit the catalytic subunit of protein kinase A. Protein inhibitor, which was described for protein kinase A, was inert for the catalytic fragment.", "contents": "Guanosine 3':5'-monophosphate-dependent protein kinase from silkworm, properties of a catalytic fragment obtained by limited proteolysis. Although guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) which was partially purified from silkworm pupae was not dissociated by cyclic GMP into catalytic and regulatory subunits as described for adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) (Takai, Y., Nakaya, S., Inoue, M., Kishimoto, A., Nishiyama, K., Yamamura, H., and Nishizuka, Y. (1976) J. Biol. Chem. 251, 1481-1487), limited proteolysis with trypsin resulted in the formation of catalytic and cyclic GMP-binding fragments which showed molecular weights of approximately 3.4 X 10(4) and 3.6 X 10(4), respectively (the molecular weight of native protein kinase G was 1.4 X 10(5)). The catalytic fragment did not bind cyclic GMP and was fully active in the absence of the cyclic nucleotide. The fragment did not show an absolute requirement for a sulfhydryl compound and high concentrations of Mg2+ (50 to 100 mM), both of which were necessary for the maximal activation of native protein kinase G. The catalytic fragment was not inhibited by the cyclic GMP-binding fragment nor by the regulatory subunit of protein kinase A. Inversely, the cyclic GMP-binding fragment was unable to inhibit the catalytic subunit of protein kinase A. Protein inhibitor, which was described for protein kinase A, was inert for the catalytic fragment."} {"id": "PMID:180030", "title": "Intra-osseous glomus tumour: a case report.", "content": "A rare case of intra-osseous glomus tumour is described, together with a review of eight other reported cases. Electron microscopic studies suggest that glomus cells, the histogenesis of which has not been completely resolved, originate from smooth muscle. Studies in this case support that hypothesis: they showed the important role of contraction of the glomus cells in eliciting the peculiar type of pain.", "contents": "Intra-osseous glomus tumour: a case report. A rare case of intra-osseous glomus tumour is described, together with a review of eight other reported cases. Electron microscopic studies suggest that glomus cells, the histogenesis of which has not been completely resolved, originate from smooth muscle. Studies in this case support that hypothesis: they showed the important role of contraction of the glomus cells in eliciting the peculiar type of pain."} {"id": "PMID:180031", "title": "Laryngeal granular cell myoblastoma two case reports with radiographic demonstration.", "content": "Laryngeal granular cell myoblastoma is a rare, benign lesion. Two cases were studied by contrast laryngography and demonstrated similar, non-specific findings of a smooth, sessile mass.", "contents": "Laryngeal granular cell myoblastoma two case reports with radiographic demonstration. Laryngeal granular cell myoblastoma is a rare, benign lesion. Two cases were studied by contrast laryngography and demonstrated similar, non-specific findings of a smooth, sessile mass."} {"id": "PMID:180032", "title": "Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. IX. Specific inhibition of DNA synthesis initiation by very low density lipoprotein and possible significance to the problem of liver regeneration.", "content": "Rat serum very low density lipoprotein (VLDL) inhibits initiation of DNA synthesis in fetal rat hepatocyte cultures; cells engaged in synthesizing DNA resist inhibition. VLDL action is specific and apparently blocks prereplicative protein synthesis. These and other results, from studies of altered blood VLDL levels and [3H] thymidine incorporation into isolated liver nuclei in 70% hepatectomized normal and mutant hyperlipoproteinemic rats, as well as from infusion studies with a \"mitogenic\" hormone solution, suggest that hepatic VLDL metabolism is linked to the suppression of hepatocyte proliferation.", "contents": "Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. IX. Specific inhibition of DNA synthesis initiation by very low density lipoprotein and possible significance to the problem of liver regeneration. Rat serum very low density lipoprotein (VLDL) inhibits initiation of DNA synthesis in fetal rat hepatocyte cultures; cells engaged in synthesizing DNA resist inhibition. VLDL action is specific and apparently blocks prereplicative protein synthesis. These and other results, from studies of altered blood VLDL levels and [3H] thymidine incorporation into isolated liver nuclei in 70% hepatectomized normal and mutant hyperlipoproteinemic rats, as well as from infusion studies with a \"mitogenic\" hormone solution, suggest that hepatic VLDL metabolism is linked to the suppression of hepatocyte proliferation."} {"id": "PMID:180033", "title": "An analysis of lectin-initiated cell agglutination in a series of CHO subclones which respond morphologically to growth in dibutyryl cyclic AMP.", "content": "We have investigated the molecular basis of the agglutinability of CHO subclones which respond differentially in terms of morphology and surface architecture in the presence of dB-cAMP in the medium. We have demonstrated that the agglutinability of these subclones with both wheat germ agglutinin (WGA) and concanavalin A (Con A) probably depends on the free lateral mobility of the lectin receptor sites in the plane of the membrane. The nonagglutinable surface architecture seems to depend on the presence in the membrane of a protease-labile peptide(s), which appears to be distinct from the lectin receptors, as well as on continuous protein and RNA synthesis. This dependence on continuous transcription and translation may be related to the maintenance of the protease-labile peptide(s) in such a state as to restrict mobility of the lectin receptors. The surface architecture defined as nonagglutinable also depends on the state of polymerization of the intracellular microtubules and microfilaments. It is suggested that these microskeletal elements serve to anchor the lectin receptors in such a manner as to restrict their mobility and thereby reduce the relative agglutinability of a cell line. We suggest that control of the free mobility of both the Con A and WGA receptor sites is dependent on two constraints, one applied by protease-labile (\"surface\") membrane components and the other by components of the intracellular microskeletal system.", "contents": "An analysis of lectin-initiated cell agglutination in a series of CHO subclones which respond morphologically to growth in dibutyryl cyclic AMP. We have investigated the molecular basis of the agglutinability of CHO subclones which respond differentially in terms of morphology and surface architecture in the presence of dB-cAMP in the medium. We have demonstrated that the agglutinability of these subclones with both wheat germ agglutinin (WGA) and concanavalin A (Con A) probably depends on the free lateral mobility of the lectin receptor sites in the plane of the membrane. The nonagglutinable surface architecture seems to depend on the presence in the membrane of a protease-labile peptide(s), which appears to be distinct from the lectin receptors, as well as on continuous protein and RNA synthesis. This dependence on continuous transcription and translation may be related to the maintenance of the protease-labile peptide(s) in such a state as to restrict mobility of the lectin receptors. The surface architecture defined as nonagglutinable also depends on the state of polymerization of the intracellular microtubules and microfilaments. It is suggested that these microskeletal elements serve to anchor the lectin receptors in such a manner as to restrict their mobility and thereby reduce the relative agglutinability of a cell line. We suggest that control of the free mobility of both the Con A and WGA receptor sites is dependent on two constraints, one applied by protease-labile (\"surface\") membrane components and the other by components of the intracellular microskeletal system."} {"id": "PMID:180034", "title": "Metabolism of 125I-labeled lipoproteins by the isolated rat lung.", "content": "The capacity of the isolated perfused rat lung to metabolize the protein moieties of serum lipoproteins was assessed using homologous (rat) and heterologous (human) plasma lipoproteins. The protein and lipid moieties of the plasma lipoproteins were labeled in vivo with Na[125I]. In selected cases the lipoprotein peptides were labeled in vivo with 14C- or 3H-labeled amino acids. Uptake of lipoprotein label during perfusion was monitored by measure of losses in perfusate label and by rises in pulmonary tissue labeling as shown by radioassay and by light and electron microscope radioautography. Lipoprotein degradation was assessed by fractionation of perfusate and lung tissue radioactive material into trichloroacetic acid (TCA)-isoluble, TCA-soluble, and ether-ethanol-soluble fractions. When heparin was included in the perfusion medium, there was selective degradation of the protein portion of very low density lipoprotein (VLDL) in the perfusate and concomitant uptake of radioactive label by the lungs. Low density lipoprotein (LDL)) was neither taken up nor catabolized by the isolated rat lung in the absence or presence of heparin. By light and electron microscopy, the label was localized over the interalveolar septa, predominantly the capillary endothelium. Disappearance of TCA-insoluble radioactivity from the perfusate was associated with the generation of both TCA-soluble iodide and noniodide radioactivity. Greater than 50% of the radioactive label taken up by the lungs was found in the delipidated TCA-insoluble fraction. This study provides in vitro evidence for pulmonary catabolism of VLDL apolipoproteins and uptake of peptide catabolic products of VLDL by the lung.", "contents": "Metabolism of 125I-labeled lipoproteins by the isolated rat lung. The capacity of the isolated perfused rat lung to metabolize the protein moieties of serum lipoproteins was assessed using homologous (rat) and heterologous (human) plasma lipoproteins. The protein and lipid moieties of the plasma lipoproteins were labeled in vivo with Na[125I]. In selected cases the lipoprotein peptides were labeled in vivo with 14C- or 3H-labeled amino acids. Uptake of lipoprotein label during perfusion was monitored by measure of losses in perfusate label and by rises in pulmonary tissue labeling as shown by radioassay and by light and electron microscope radioautography. Lipoprotein degradation was assessed by fractionation of perfusate and lung tissue radioactive material into trichloroacetic acid (TCA)-isoluble, TCA-soluble, and ether-ethanol-soluble fractions. When heparin was included in the perfusion medium, there was selective degradation of the protein portion of very low density lipoprotein (VLDL) in the perfusate and concomitant uptake of radioactive label by the lungs. Low density lipoprotein (LDL)) was neither taken up nor catabolized by the isolated rat lung in the absence or presence of heparin. By light and electron microscopy, the label was localized over the interalveolar septa, predominantly the capillary endothelium. Disappearance of TCA-insoluble radioactivity from the perfusate was associated with the generation of both TCA-soluble iodide and noniodide radioactivity. Greater than 50% of the radioactive label taken up by the lungs was found in the delipidated TCA-insoluble fraction. This study provides in vitro evidence for pulmonary catabolism of VLDL apolipoproteins and uptake of peptide catabolic products of VLDL by the lung."} {"id": "PMID:180035", "title": "Regular structures in unit membranes. II. Morphological and biochemical characterization of two water-soluble membrane proteins isolated from the suckling rat ileum.", "content": "Specialized plasma membranes from the endocytic complex of ileal epithelial cells of suckling rats were isolated by differential flotation. Thin-section and negative-stain electron microscopy showed the luminal surfaces of these membranes to be covered by an ordered array of particles 14.5-nm separations in long rows. This particulate coating was released from the membrane surfaces by 10 mM CaCl2 and recovered free of membranes after dialysis against 0.5 mM EGTA and high-speed centrifugation. Two proteins were resolved by gel filtration to be in supernate: n-acetyl-beta-glucosaminidase and a filamentous protein which attaches n-acetylglucosaminidase to the membrane surface thereby providing bidirectionality to the array of enzyme. We believe that the filamentous protein has not been previously described. Therefore we have called it ligatin from the latin ligare, which translates \"to bind together\". Furthermore, we suggest that the membranes of the endocytic complex contain sites for the extracellular digestion of carbohydrate moieties in the maternal milk.", "contents": "Regular structures in unit membranes. II. Morphological and biochemical characterization of two water-soluble membrane proteins isolated from the suckling rat ileum. Specialized plasma membranes from the endocytic complex of ileal epithelial cells of suckling rats were isolated by differential flotation. Thin-section and negative-stain electron microscopy showed the luminal surfaces of these membranes to be covered by an ordered array of particles 14.5-nm separations in long rows. This particulate coating was released from the membrane surfaces by 10 mM CaCl2 and recovered free of membranes after dialysis against 0.5 mM EGTA and high-speed centrifugation. Two proteins were resolved by gel filtration to be in supernate: n-acetyl-beta-glucosaminidase and a filamentous protein which attaches n-acetylglucosaminidase to the membrane surface thereby providing bidirectionality to the array of enzyme. We believe that the filamentous protein has not been previously described. Therefore we have called it ligatin from the latin ligare, which translates \"to bind together\". Furthermore, we suggest that the membranes of the endocytic complex contain sites for the extracellular digestion of carbohydrate moieties in the maternal milk."} {"id": "PMID:180036", "title": "BHK21 fibroblast aggregation inhibited by glycopeptides from the cell surface.", "content": "Glycopeptides were removed by trypsinization from the surface of baby hamster kidney cells (line BHK21-C13), digested by pronase and separated into 2 fractions by exclusion chromatography. The addition of small amounts of either glycopeptide fraction to shaken suspensions of lightly trypsinzied cells inhibited their rapid aggregation, but one fraction was more active than the other and in higher concentrations it was able to inhibit aggregation completely. After this fraction was purified by high-voltage electrophoresis one subfraction also inhibited aggregation. The effect of the glycopeptides increased following their pretreatment with neuraminidase, but preincubation with periodiate or galactose oxidase destroyed all activity. Galactose oxidase also inhibited cell aggregation directly. Similar glycopeptides from virus-transformed BHK21 cells, oligosaccharides and intact and desialysed human urinary glycoproteins had comparatively little or no effect on BHK21 cell aggregation. The results suggest terminal beta-galactosides and possible alpha-galactosides, and to some extent a particular substructure of cell surface heteroglycans are necessary for their inhibitory activity. The parent, plasma membrane of glycoproteins might serve as adhesive binding sites in cell cohesion, but some evidence indicates cell surface sialyl- and galactosyltransferases may not ordinarily act as their complementary binding receptors.", "contents": "BHK21 fibroblast aggregation inhibited by glycopeptides from the cell surface. Glycopeptides were removed by trypsinization from the surface of baby hamster kidney cells (line BHK21-C13), digested by pronase and separated into 2 fractions by exclusion chromatography. The addition of small amounts of either glycopeptide fraction to shaken suspensions of lightly trypsinzied cells inhibited their rapid aggregation, but one fraction was more active than the other and in higher concentrations it was able to inhibit aggregation completely. After this fraction was purified by high-voltage electrophoresis one subfraction also inhibited aggregation. The effect of the glycopeptides increased following their pretreatment with neuraminidase, but preincubation with periodiate or galactose oxidase destroyed all activity. Galactose oxidase also inhibited cell aggregation directly. Similar glycopeptides from virus-transformed BHK21 cells, oligosaccharides and intact and desialysed human urinary glycoproteins had comparatively little or no effect on BHK21 cell aggregation. The results suggest terminal beta-galactosides and possible alpha-galactosides, and to some extent a particular substructure of cell surface heteroglycans are necessary for their inhibitory activity. The parent, plasma membrane of glycoproteins might serve as adhesive binding sites in cell cohesion, but some evidence indicates cell surface sialyl- and galactosyltransferases may not ordinarily act as their complementary binding receptors."} {"id": "PMID:180037", "title": "[Masson's tumor of the fingers].", "content": "The authors report three cases of glomus tumour of the fingers and conclude, from the angiographic appearance, that the glomus tumour presents direct and indirect signs suggesting the lesion.", "contents": "[Masson's tumor of the fingers]. The authors report three cases of glomus tumour of the fingers and conclude, from the angiographic appearance, that the glomus tumour presents direct and indirect signs suggesting the lesion."} {"id": "PMID:180038", "title": "[Quantitative separation of biological lipids by successive chromatographic runs on juxtaposed thin layers (author's transl)].", "content": "During a study on incorporation of 14C-labeled precursors in biological lipids, we had to elaborate a method of quantitative separation of lipid classes, based upon three successive chromatographic runs on juxtaposed thin layers. The first thin layer, on which the lipid extract is applied, consists of silica gel alkalised by means of sodium hydroxide solution. The second thin layer is constituted only by silica gel G. The three one-dimensional migrations are respectively carried out in the following solvent systems: diethyl ether-hexane-benzene (55:30:15), hexane-benzene (80:20) and diethyl ether-benzene-acetic acid (62:20:18). The lipid fractions are scraped out and counted by liquid scintillation. The reproducibility of the whole operation is discussed.", "contents": "[Quantitative separation of biological lipids by successive chromatographic runs on juxtaposed thin layers (author's transl)]. During a study on incorporation of 14C-labeled precursors in biological lipids, we had to elaborate a method of quantitative separation of lipid classes, based upon three successive chromatographic runs on juxtaposed thin layers. The first thin layer, on which the lipid extract is applied, consists of silica gel alkalised by means of sodium hydroxide solution. The second thin layer is constituted only by silica gel G. The three one-dimensional migrations are respectively carried out in the following solvent systems: diethyl ether-hexane-benzene (55:30:15), hexane-benzene (80:20) and diethyl ether-benzene-acetic acid (62:20:18). The lipid fractions are scraped out and counted by liquid scintillation. The reproducibility of the whole operation is discussed."} {"id": "PMID:180039", "title": "[Lysergic acids. II. Isolation and separation of lysergic acids (author's transl)].", "content": "During studies on the isolation of both lysergic acids, D-and D-iso-, from hydrolytic mixtures of ergot alkaloids, it became necessary to find a simple chromatographic system for column isolation of lysergic acids. The column with controlled pore glass is highly effective for these purposes. The separation of both isomeric lysergic acids occurs on the column with silica gel. The assay and the composition of lysergic acid are estimated by thin-layer chromatography on precoated plates.", "contents": "[Lysergic acids. II. Isolation and separation of lysergic acids (author's transl)]. During studies on the isolation of both lysergic acids, D-and D-iso-, from hydrolytic mixtures of ergot alkaloids, it became necessary to find a simple chromatographic system for column isolation of lysergic acids. The column with controlled pore glass is highly effective for these purposes. The separation of both isomeric lysergic acids occurs on the column with silica gel. The assay and the composition of lysergic acid are estimated by thin-layer chromatography on precoated plates."} {"id": "PMID:180040", "title": "Forensic aspects of high-pressure liquid chromatography.", "content": "This paper reviews the applications of high-pressure liquid chromatography (HPLC) to forensic problems, and discusses some of the developments that have taken place in the use of the technique in the Metropolitan Police Laboratory. Preparation of octadecyltrichlorosilane-modified silica is described and some of the chromatographic characteristics of this material are investigated. Applications of HPLC to the analysis of cannabis, opium alkaloids, amphetamine-related materials, LSD and polynuclear hydrocarbons are described.", "contents": "Forensic aspects of high-pressure liquid chromatography. This paper reviews the applications of high-pressure liquid chromatography (HPLC) to forensic problems, and discusses some of the developments that have taken place in the use of the technique in the Metropolitan Police Laboratory. Preparation of octadecyltrichlorosilane-modified silica is described and some of the chromatographic characteristics of this material are investigated. Applications of HPLC to the analysis of cannabis, opium alkaloids, amphetamine-related materials, LSD and polynuclear hydrocarbons are described."} {"id": "PMID:180041", "title": "Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal androgen secretion.", "content": "Dehydroepiandrosterone sulfate (DS) concentration was measured in the sera of premature and full-term infants and in children throughout puberty. Panhypopituitary, Addisonian, and virilized children were also studied. DS decreased slowly during the first weeks of life from a high level in neonates to the low levels observed between one to five years. After five years of age, DS concentration started to rise. A steeper increase was observed with the onset of puberty, and adult DS concentrations were reached in late puberty. There was no sex difference in DS concentration at any pubertal stage or bone age. Day-to-day variations were small in childhood and during puberty, but were considerable in premature infants. DS concentrations measured at 0900 h were not significantly different from those at 1700 h. There was a positive correlation of serum DS concentrations with the excretion of urinary 17-ketosteroids in boys and girls (r=0.789). Premature infants had DS concentration in or above the late pubertal range. Five panhypopituitary patients and five Addisonian patients had DS concentrations below normal. DS was markedly elevated in patients with congenital adrenal hyperplasia and in one girl with adrenal carcinoma, and was suppressible with dexamethasone in the former. The ease of measurement and the small amount of blood required make serum DS determination a useful guide for adrenal androgen secretion.", "contents": "Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal androgen secretion. Dehydroepiandrosterone sulfate (DS) concentration was measured in the sera of premature and full-term infants and in children throughout puberty. Panhypopituitary, Addisonian, and virilized children were also studied. DS decreased slowly during the first weeks of life from a high level in neonates to the low levels observed between one to five years. After five years of age, DS concentration started to rise. A steeper increase was observed with the onset of puberty, and adult DS concentrations were reached in late puberty. There was no sex difference in DS concentration at any pubertal stage or bone age. Day-to-day variations were small in childhood and during puberty, but were considerable in premature infants. DS concentrations measured at 0900 h were not significantly different from those at 1700 h. There was a positive correlation of serum DS concentrations with the excretion of urinary 17-ketosteroids in boys and girls (r=0.789). Premature infants had DS concentration in or above the late pubertal range. Five panhypopituitary patients and five Addisonian patients had DS concentrations below normal. DS was markedly elevated in patients with congenital adrenal hyperplasia and in one girl with adrenal carcinoma, and was suppressible with dexamethasone in the former. The ease of measurement and the small amount of blood required make serum DS determination a useful guide for adrenal androgen secretion."} {"id": "PMID:180042", "title": "Testosterone-estradiol-binding globulin in patients with Turner's syndrome: effects of estrogens and acute growth hormone administration.", "content": "The TeBG activity of plasma from patients with Turner's syndrome was measured quantitatively using polyacrylamide gel electrophoresis. Human growth hormone administration did not significantly change the plasma TeBG levels. However, oral replacement therapy with estrogens elevated plasma TeBG within 3 days; after 9 days these levels reached a maximum of three- to four-fold greater than that observed at a time prior to therapy.", "contents": "Testosterone-estradiol-binding globulin in patients with Turner's syndrome: effects of estrogens and acute growth hormone administration. The TeBG activity of plasma from patients with Turner's syndrome was measured quantitatively using polyacrylamide gel electrophoresis. Human growth hormone administration did not significantly change the plasma TeBG levels. However, oral replacement therapy with estrogens elevated plasma TeBG within 3 days; after 9 days these levels reached a maximum of three- to four-fold greater than that observed at a time prior to therapy."} {"id": "PMID:180043", "title": "Evidence for altered synthesis of human chorionic gonadotropin in gestational trophoblastic tumors.", "content": "Tissue extracts of molar tissue or choriocarcinoma, blood, or urine of 21 women with gestational trophoblastic disease were analyzed for hCG and its subunits. The extracts or biologic fluids were initially chromatographed through a standardized Sephadex G-100 column. Each fraction was radioimmunoassayed in homologous hCG, hCGalpha, and hCGbeta assays. Extracts of four hydatidiform moles contained primarily hCG but no free alpha subunit of that hormone. One of the molar extracts contained a small amount of free hCGbeta not observed in the small amount of free hCGbeta not observed in the extracts of the other three moles. Plasma and urine samples from 18 women with localized or metastatic gestational trophoblastic disease contained hCG but no free alpha or beta subunits; the neoplasms of those patients readily responded to chemotherapy, and all patients have had no evidence of disease for at least one year. The major portion of immunologic hCG present in the biologic samples was indistinguishable from native hCG in its physical behavior on Sephadex G-100 chromatography. On the other hand, three women with widely metastatic tumors died in spite of extensive chemotherapy. Extracts of tumors from two of those patients contained hCG and free subunits of hCG. The urine and plasma of the third patient contained hCG and hCGalpha with the concentration of hCGalpha far exceeding that for hCG in urine. The results of these studies clearly show a disparity between the forms of hCG found in the normal placenta and pregnancy sera, as previously reported, and those found in the neoplastic trophoblast with varying degrees of anaplasia. The most striking finding was the absence of free circulating hCGalpha in the sera in patients with gestational trophoblastic disease which responded to chemotherapy, since free hCGalpha is readily detectable in the sera of normally pregnant women.", "contents": "Evidence for altered synthesis of human chorionic gonadotropin in gestational trophoblastic tumors. Tissue extracts of molar tissue or choriocarcinoma, blood, or urine of 21 women with gestational trophoblastic disease were analyzed for hCG and its subunits. The extracts or biologic fluids were initially chromatographed through a standardized Sephadex G-100 column. Each fraction was radioimmunoassayed in homologous hCG, hCGalpha, and hCGbeta assays. Extracts of four hydatidiform moles contained primarily hCG but no free alpha subunit of that hormone. One of the molar extracts contained a small amount of free hCGbeta not observed in the small amount of free hCGbeta not observed in the extracts of the other three moles. Plasma and urine samples from 18 women with localized or metastatic gestational trophoblastic disease contained hCG but no free alpha or beta subunits; the neoplasms of those patients readily responded to chemotherapy, and all patients have had no evidence of disease for at least one year. The major portion of immunologic hCG present in the biologic samples was indistinguishable from native hCG in its physical behavior on Sephadex G-100 chromatography. On the other hand, three women with widely metastatic tumors died in spite of extensive chemotherapy. Extracts of tumors from two of those patients contained hCG and free subunits of hCG. The urine and plasma of the third patient contained hCG and hCGalpha with the concentration of hCGalpha far exceeding that for hCG in urine. The results of these studies clearly show a disparity between the forms of hCG found in the normal placenta and pregnancy sera, as previously reported, and those found in the neoplastic trophoblast with varying degrees of anaplasia. The most striking finding was the absence of free circulating hCGalpha in the sera in patients with gestational trophoblastic disease which responded to chemotherapy, since free hCGalpha is readily detectable in the sera of normally pregnant women."} {"id": "PMID:180044", "title": "Effects of ACTH on steroid metabolism.", "content": "Metabolic clearance rates (MCR) of aldosterone, cortisol, DOC, corticosterone, and progesterone were simultaneously measured by constant infusion in 8 control subjects before and during an ACTH infusion (12.5 U/4 h). Plasma levels of aldosterone and cortisol, the heat-labile plasma protein-bound fraction of aldosterone, and hepatic blood flow as estimated by the fractional clearance of indocyanine green, were concomitantly determined. The mean MCR of aldosterone, cortisol, and DOC increased to a peak value of 26%, 23%, and 22%, respectively, above baseline values. The increase was already significant (P is less than 0.001) 30 min after the beginning of the ACTH infusion. In contrast, no consistent changes occurred in the MCR of corticosterone and progesterone or in hepatic blood flow. ACTH induced a marked fall in the heat-labile plasma protein-bound fraction of aldosterone. Plasma levels of aldosterone and corsitol increased by 190 and 250%, respectively. A significant negative correlation (r=-0.423, P is less than 0.01) between the MCR and the heat-labile protein-bound fraction of aldosterone was observed. We suggest that competitive interactions in the protein binding properties of various steroids account for the selective effect of ACTH on the MCR of aldosterone, cortisol, and DOC.", "contents": "Effects of ACTH on steroid metabolism. Metabolic clearance rates (MCR) of aldosterone, cortisol, DOC, corticosterone, and progesterone were simultaneously measured by constant infusion in 8 control subjects before and during an ACTH infusion (12.5 U/4 h). Plasma levels of aldosterone and cortisol, the heat-labile plasma protein-bound fraction of aldosterone, and hepatic blood flow as estimated by the fractional clearance of indocyanine green, were concomitantly determined. The mean MCR of aldosterone, cortisol, and DOC increased to a peak value of 26%, 23%, and 22%, respectively, above baseline values. The increase was already significant (P is less than 0.001) 30 min after the beginning of the ACTH infusion. In contrast, no consistent changes occurred in the MCR of corticosterone and progesterone or in hepatic blood flow. ACTH induced a marked fall in the heat-labile plasma protein-bound fraction of aldosterone. Plasma levels of aldosterone and corsitol increased by 190 and 250%, respectively. A significant negative correlation (r=-0.423, P is less than 0.01) between the MCR and the heat-labile protein-bound fraction of aldosterone was observed. We suggest that competitive interactions in the protein binding properties of various steroids account for the selective effect of ACTH on the MCR of aldosterone, cortisol, and DOC."} {"id": "PMID:180045", "title": "Observations on the cyclic nucleotide concentrations in human cerebrospinal fluid.", "content": "Previous studies have shown that the concentrations of 3', 5' cyclic adenosine monophosphate (cAMP) and 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF), brain, or both, are increased by melanotropic peptides and catechol amines, and by cholinergic agents. The present study measured the concentrations of cAMP, cGMP, and melanotropic activity in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF, concentrations (ave +/- SD) were: cAMP, 21 +/- 8 mM; cGMP, 2.4 +/- 0.5 mM; melanotropic activity, 17 +/- 6 units/100 ml. Concentrations of cAMP, cGMP, and melanotropic activity did not differ significantly (P is less than .05) from normal in the following categories of adult and pediatric patients: back pain due to vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These two variables were significantly correlated in the entire series of CSF samples (r=+0.55, P is less than .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide's level rose as high as 50 X normal when ventricular pressure exceeded 300 mm H2O. The concentration of ventricular cGMP was proportional to that of ventricular pressure (r=+0.76, P is less than .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient, or the nature of the underlying disease.", "contents": "Observations on the cyclic nucleotide concentrations in human cerebrospinal fluid. Previous studies have shown that the concentrations of 3', 5' cyclic adenosine monophosphate (cAMP) and 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF), brain, or both, are increased by melanotropic peptides and catechol amines, and by cholinergic agents. The present study measured the concentrations of cAMP, cGMP, and melanotropic activity in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF, concentrations (ave +/- SD) were: cAMP, 21 +/- 8 mM; cGMP, 2.4 +/- 0.5 mM; melanotropic activity, 17 +/- 6 units/100 ml. Concentrations of cAMP, cGMP, and melanotropic activity did not differ significantly (P is less than .05) from normal in the following categories of adult and pediatric patients: back pain due to vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These two variables were significantly correlated in the entire series of CSF samples (r=+0.55, P is less than .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide's level rose as high as 50 X normal when ventricular pressure exceeded 300 mm H2O. The concentration of ventricular cGMP was proportional to that of ventricular pressure (r=+0.76, P is less than .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient, or the nature of the underlying disease."} {"id": "PMID:180046", "title": "Method for preparation of ampoules containing microgram quantities of polypeptide hormones for distribution and use as laboratory standards: synthetic human ACTH and beta-MSH.", "content": "There are a number of polypeptide hormones, their subunits, and other derivatives that are available in such short supply as to preclude distribution by conventional methods to the many qualified investigators who require them. This report describes a method for preparing sealed ampoules of two such hormones, the utilization of which can provide many qualified investigators with comparable, stable reference compounds for several years and eliminate unnecessary waste and error associated with the distribution and use of bulk quantitites of peptide hormone preparations. Sealed ampoules of synthetic human adrenocorticotrophic hormone (alpha(h)(1-39) ACTH) and beta melanocyte-stimulating hormone (beta(h)(1-22) MSH) were prepared. Each ampuole contains 50 mug of dried and recoverable peptide plus 1 mg of lactose, sealed under dry nitrogen at atmospheric pressure. The respective preparations are fully active, both biologically and radioimmunologically, and are suitable as reference compounds in all types of biologic and radioimmunologic assays of these hormones. In addition, radioactive iodine labeling of each peptide can be accomplished without prior removal of the lactose.", "contents": "Method for preparation of ampoules containing microgram quantities of polypeptide hormones for distribution and use as laboratory standards: synthetic human ACTH and beta-MSH. There are a number of polypeptide hormones, their subunits, and other derivatives that are available in such short supply as to preclude distribution by conventional methods to the many qualified investigators who require them. This report describes a method for preparing sealed ampoules of two such hormones, the utilization of which can provide many qualified investigators with comparable, stable reference compounds for several years and eliminate unnecessary waste and error associated with the distribution and use of bulk quantitites of peptide hormone preparations. Sealed ampoules of synthetic human adrenocorticotrophic hormone (alpha(h)(1-39) ACTH) and beta melanocyte-stimulating hormone (beta(h)(1-22) MSH) were prepared. Each ampuole contains 50 mug of dried and recoverable peptide plus 1 mg of lactose, sealed under dry nitrogen at atmospheric pressure. The respective preparations are fully active, both biologically and radioimmunologically, and are suitable as reference compounds in all types of biologic and radioimmunologic assays of these hormones. In addition, radioactive iodine labeling of each peptide can be accomplished without prior removal of the lactose."} {"id": "PMID:180047", "title": "Laboratory investigation of diarrhea in travelers to Mexico: evaluation of methods for detecting enterotoxigenic Echerichia coli.", "content": "A laboratory investigation was conducted on cultures collected from travelers before, during, and after a trip to Mexico to characterize the etiology of traveler's diarrhea. Four laboratory methods for detecting enterotoxigenicity of Escherichia coli were evaluated: the infant mouse assay, the Chinese hamster ovary (CHO) cell assay, the Y1 adrenal cell assay, and the rabbit ileal loop. Although a number of common enteric pathogens were identified as a cause of traveler's diarrhea, including six serotypes of Salmonella, two serotypes of Shigella, Vibrio parahaemolyticus, Giardia lamblia, and Entamoeba histolytica, enterotoxigenic Escherichia coli was most commonly isolated. Strains were identified that produced only heat-labile enterotoxin (LT), only heat-stable enterotoxin (ST), or both LT and ST. The infant mouse assay yielded results falling into two distinct groups, providing a clear separation of positive and negative cultures. The CHO assay also formed two groups, with positive cultures producing 11% or more of the elongated cells. There was good agreement between the CHO and the Y1 adrenal cell assays for detection of LT. The adrenal cell system for detection of LT was more suitable than the CHO assay for processing large numbers of specimens because of the miniculture modification of this method utilized in this study. The infant mouse method was a simple and reliable method for detecting ST.", "contents": "Laboratory investigation of diarrhea in travelers to Mexico: evaluation of methods for detecting enterotoxigenic Echerichia coli. A laboratory investigation was conducted on cultures collected from travelers before, during, and after a trip to Mexico to characterize the etiology of traveler's diarrhea. Four laboratory methods for detecting enterotoxigenicity of Escherichia coli were evaluated: the infant mouse assay, the Chinese hamster ovary (CHO) cell assay, the Y1 adrenal cell assay, and the rabbit ileal loop. Although a number of common enteric pathogens were identified as a cause of traveler's diarrhea, including six serotypes of Salmonella, two serotypes of Shigella, Vibrio parahaemolyticus, Giardia lamblia, and Entamoeba histolytica, enterotoxigenic Escherichia coli was most commonly isolated. Strains were identified that produced only heat-labile enterotoxin (LT), only heat-stable enterotoxin (ST), or both LT and ST. The infant mouse assay yielded results falling into two distinct groups, providing a clear separation of positive and negative cultures. The CHO assay also formed two groups, with positive cultures producing 11% or more of the elongated cells. There was good agreement between the CHO and the Y1 adrenal cell assays for detection of LT. The adrenal cell system for detection of LT was more suitable than the CHO assay for processing large numbers of specimens because of the miniculture modification of this method utilized in this study. The infant mouse method was a simple and reliable method for detecting ST."} {"id": "PMID:180048", "title": "Comparison of rhinovirus-sensitive HeLa cells and human embryo fibroblasts for isolation of rhinoviruses from patients with respiratory disease.", "content": "Rhinovirus-sensitive HeLa cells (HeLa \"R\") and human embryo lung fibroblasts (HEL) were compared for the isolation of rhinoviruses from patients with respiratory disease. In the period May 1970 to December 1974, 526 rhinoviruses were isolated from 517 patients, 32% in both cell types, 59% in HeLa \"R\" only, and 9% in HEL only. The annual isolations in HeLa \"R\" were between 1.7 and 4 times greater than in HEL cells and may have been due to changes in the sensitivity of the cells or the prevalence of serotypes favoring the HeLa \"R\" cells. Acid lability was more easily demonstrated in HeLa \"R\" than in HEL cells, because the infectivity titers obtained were 10- to 100-fold higher.", "contents": "Comparison of rhinovirus-sensitive HeLa cells and human embryo fibroblasts for isolation of rhinoviruses from patients with respiratory disease. Rhinovirus-sensitive HeLa cells (HeLa \"R\") and human embryo lung fibroblasts (HEL) were compared for the isolation of rhinoviruses from patients with respiratory disease. In the period May 1970 to December 1974, 526 rhinoviruses were isolated from 517 patients, 32% in both cell types, 59% in HeLa \"R\" only, and 9% in HEL only. The annual isolations in HeLa \"R\" were between 1.7 and 4 times greater than in HEL cells and may have been due to changes in the sensitivity of the cells or the prevalence of serotypes favoring the HeLa \"R\" cells. Acid lability was more easily demonstrated in HeLa \"R\" than in HEL cells, because the infectivity titers obtained were 10- to 100-fold higher."} {"id": "PMID:180049", "title": "Application of a new method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase to various M types of Streptoccus pyogenes.", "content": "The production of extracellular nicotinamide adenine dinucleotide glycohydrolase (NADase) by Streptococcus pyogenes can easily be demonstrated using the fluorescence of nicotinamide adenine dinucleotide in ultraviolet light occurring on addition of strong alkali. The new method described here uses microtiter plates and can be read with the naked eye. It permits the screening of large numbers of strains in a short time and with minimal amounts of reagents. The sensitivity of the new method proved to be good in comparison with the bisulfite spectrophotometric method. Culture supernatants of 177 group A streptococci were tested for NADase production by the microtiter fluorescence method. We could confirm former findings that strains within a certain M type of S. pyogenes are usually either producers or nonproducers of the enzyme. The usefulness of the test for screening of streptococcal NADase production is discussed.", "contents": "Application of a new method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase to various M types of Streptoccus pyogenes. The production of extracellular nicotinamide adenine dinucleotide glycohydrolase (NADase) by Streptococcus pyogenes can easily be demonstrated using the fluorescence of nicotinamide adenine dinucleotide in ultraviolet light occurring on addition of strong alkali. The new method described here uses microtiter plates and can be read with the naked eye. It permits the screening of large numbers of strains in a short time and with minimal amounts of reagents. The sensitivity of the new method proved to be good in comparison with the bisulfite spectrophotometric method. Culture supernatants of 177 group A streptococci were tested for NADase production by the microtiter fluorescence method. We could confirm former findings that strains within a certain M type of S. pyogenes are usually either producers or nonproducers of the enzyme. The usefulness of the test for screening of streptococcal NADase production is discussed."} {"id": "PMID:180050", "title": "Suppression by cyproheptadine of human growth hormone and cortisol secretion during sleep.", "content": "The effect of cyproheptadine on plasma growth hormone and cortisol levels was studied in seven male volunteers with polygraphic sleep monitoring. Sleep-related growth hormone release was completely inhibited in three of the seven normal subjects by the intravenous infusion of cyproheptadine (5 mg) which was started at the onset of sleep. In the other four, growth hormone release during sleep was significantly decreased or delayed by cyproheptadine when the drug infusion was started at 7:00 p.m., 1-2 h before the onset of sleep. The usual increase in plasma cortisol in the early morning was completely suppressed in all five subjects given cyproheptadine infusions from 4:00 to 7:00 a.m. The intravenous infusion of cyproheptadine increased slow wave sleep, although the time from sleep onset to the first occurrence of slow wave sleep was not affected. In contrast, rapid eye movement sleep was significantly decreased by cyproheptadine. These results suggest that cyproheptadine inhibits growth hormone and ACTH secretion during sleep in man, possibly by antagonizing serotoninergic mechanisms although other actions of the drug are not ruled out.", "contents": "Suppression by cyproheptadine of human growth hormone and cortisol secretion during sleep. The effect of cyproheptadine on plasma growth hormone and cortisol levels was studied in seven male volunteers with polygraphic sleep monitoring. Sleep-related growth hormone release was completely inhibited in three of the seven normal subjects by the intravenous infusion of cyproheptadine (5 mg) which was started at the onset of sleep. In the other four, growth hormone release during sleep was significantly decreased or delayed by cyproheptadine when the drug infusion was started at 7:00 p.m., 1-2 h before the onset of sleep. The usual increase in plasma cortisol in the early morning was completely suppressed in all five subjects given cyproheptadine infusions from 4:00 to 7:00 a.m. The intravenous infusion of cyproheptadine increased slow wave sleep, although the time from sleep onset to the first occurrence of slow wave sleep was not affected. In contrast, rapid eye movement sleep was significantly decreased by cyproheptadine. These results suggest that cyproheptadine inhibits growth hormone and ACTH secretion during sleep in man, possibly by antagonizing serotoninergic mechanisms although other actions of the drug are not ruled out."} {"id": "PMID:180051", "title": "Hormonal modulation of cyclic adenosine 3',5'-monophosphate-dependent protein kinase activity in rat renal cortex. Specificity of enzyme translocation.", "content": "Many of the intracellular actions of cyclic adenosine 3',5'-monophosphate are expressed through phosphorylation reactions mediated by cAMP-dependent protein kinases, but little is known about hormonal control of endogenous protein kinase activity (PK) in kidney. In the present study, we examined the effects of parathyroid hormone, glucagon, and isoproterenol on cAMP and PK in slices of rat renal cortex. In the presence of 0.5 mM 1-methyl, 3-isobutyl xanthine, all three hormones activated PK in slices, as reflected by an increase in the ratio of enzyme activity assayable in homogenates of the slices without addition of cAMP to the kinase reaction mixture (cAMP-independent activity) over total enzyme activity (+2 uM cAMP in the reaction mixture). When enzyme activity was assayed in whole homogenates prepared from slices, the increase in the enzyme activity ratio (- cAMP/+cAMP) which followed hormonal stimulation was due entirely to an increase in cAMP-independent activity, with no change in total activity. In general, a good correlation existed between the alterations in tissue cAMP levels mediated by the hormones and/or 1-methyl, 3-isobutyl xanthine and concomitant alterations in PK. All three hormones increased PK activity ratios to near unity, suggesting complete enzyme activation. However, the concentrations of parathyroid hormone and glucagon which produced maximal activation of PK were much lower than those required for maximal cAMP responses. Studies with charcoal indicated that these hormonal actions on PK reflected intracellular events rather than representing activation of the enzyme during tissue homogenization, due to release of sequestered cAMP. Thus, homogenization of tissue in charcoal prevented activation of PK by subsequent addition of exogenous cAMP, but did not lower enzyme activity ratios in homogenates of hormone-stimulated cortical slices. When PK was determined in the 20,000 g supernatant fraction of renal cortical slices incubated with the hormones, enzyme activity ratios also increased, but total enzyme activity declined. Lost activity was recovered by extraction of particulate fractions with 500 mM KCl or NaCl, results which implied particulate binding of activated PK. Activated soluble PK from renal cortex was bound equally well by intact, heat- and trypsin-treated renal cortical pellets and by intact and heated hepatic pellets. Accordingly, the apparent translocation of enzyme in hormone stimulated cortex does not necessarily represent binding of the activated PK to specific acceptor sites in the particulate cell fractions or constitute a physiologic hormonal action. Activation of renal cortical PK by increasing concentrations of salts suggests that the enzyme in this tissue resembles the predominant type found in heart.", "contents": "Hormonal modulation of cyclic adenosine 3',5'-monophosphate-dependent protein kinase activity in rat renal cortex. Specificity of enzyme translocation. Many of the intracellular actions of cyclic adenosine 3',5'-monophosphate are expressed through phosphorylation reactions mediated by cAMP-dependent protein kinases, but little is known about hormonal control of endogenous protein kinase activity (PK) in kidney. In the present study, we examined the effects of parathyroid hormone, glucagon, and isoproterenol on cAMP and PK in slices of rat renal cortex. In the presence of 0.5 mM 1-methyl, 3-isobutyl xanthine, all three hormones activated PK in slices, as reflected by an increase in the ratio of enzyme activity assayable in homogenates of the slices without addition of cAMP to the kinase reaction mixture (cAMP-independent activity) over total enzyme activity (+2 uM cAMP in the reaction mixture). When enzyme activity was assayed in whole homogenates prepared from slices, the increase in the enzyme activity ratio (- cAMP/+cAMP) which followed hormonal stimulation was due entirely to an increase in cAMP-independent activity, with no change in total activity. In general, a good correlation existed between the alterations in tissue cAMP levels mediated by the hormones and/or 1-methyl, 3-isobutyl xanthine and concomitant alterations in PK. All three hormones increased PK activity ratios to near unity, suggesting complete enzyme activation. However, the concentrations of parathyroid hormone and glucagon which produced maximal activation of PK were much lower than those required for maximal cAMP responses. Studies with charcoal indicated that these hormonal actions on PK reflected intracellular events rather than representing activation of the enzyme during tissue homogenization, due to release of sequestered cAMP. Thus, homogenization of tissue in charcoal prevented activation of PK by subsequent addition of exogenous cAMP, but did not lower enzyme activity ratios in homogenates of hormone-stimulated cortical slices. When PK was determined in the 20,000 g supernatant fraction of renal cortical slices incubated with the hormones, enzyme activity ratios also increased, but total enzyme activity declined. Lost activity was recovered by extraction of particulate fractions with 500 mM KCl or NaCl, results which implied particulate binding of activated PK. Activated soluble PK from renal cortex was bound equally well by intact, heat- and trypsin-treated renal cortical pellets and by intact and heated hepatic pellets. Accordingly, the apparent translocation of enzyme in hormone stimulated cortex does not necessarily represent binding of the activated PK to specific acceptor sites in the particulate cell fractions or constitute a physiologic hormonal action. Activation of renal cortical PK by increasing concentrations of salts suggests that the enzyme in this tissue resembles the predominant type found in heart."} {"id": "PMID:180052", "title": "Tissue T and B cell infiltration of primary and metastatic cancer.", "content": "Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.", "contents": "Tissue T and B cell infiltration of primary and metastatic cancer. Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer."} {"id": "PMID:180053", "title": "Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.", "content": "In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.", "contents": "Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs. In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1."} {"id": "PMID:180054", "title": "Defect in intracellular killing of Staphylococcus aureus within alveolar macrophages in Sendai virus-infected murine lungs.", "content": "Bacterial multiplication associated with virus infections is related to defects in in situ bactericidal (phagocytic) mechanisms of the lung. To determine whether the phagocytic defect was in bacterial ingestion and/or intracellular digestion, mice were infected with a sublethal dose of aerosolized Sendai virus and challenged 7 days later with a finely dispersed aerosol of Staphylococcus aureus. Groups of uninfected and virus-infected mice were sacrificed at 0, 6, 12, and 24 h after challenge, the lungs were perfused with formalin in situ, and the intra- or extracellular location of the bacteria was determined histologically. At 0 h, 49% and 51% of the staphylococci had an intracellular location in virus and nonvirus-infected lungs, respectively. With time, decreasing numbers of staphylococci were observed within the phagocytic cells of nonvirus-infected lungs, mostly as single organisms or in small clusters of less than four. In contrast, in focal area of virus-infected lungs, increasing numbers of phagocytic cells showed clumps of more than 25 bacteria/cell. These data demonstrate that virus-infected suppression of pulmonary antibacterial activity against S. aureus is related primarily to defects in intracellular processing mechanisms.", "contents": "Defect in intracellular killing of Staphylococcus aureus within alveolar macrophages in Sendai virus-infected murine lungs. Bacterial multiplication associated with virus infections is related to defects in in situ bactericidal (phagocytic) mechanisms of the lung. To determine whether the phagocytic defect was in bacterial ingestion and/or intracellular digestion, mice were infected with a sublethal dose of aerosolized Sendai virus and challenged 7 days later with a finely dispersed aerosol of Staphylococcus aureus. Groups of uninfected and virus-infected mice were sacrificed at 0, 6, 12, and 24 h after challenge, the lungs were perfused with formalin in situ, and the intra- or extracellular location of the bacteria was determined histologically. At 0 h, 49% and 51% of the staphylococci had an intracellular location in virus and nonvirus-infected lungs, respectively. With time, decreasing numbers of staphylococci were observed within the phagocytic cells of nonvirus-infected lungs, mostly as single organisms or in small clusters of less than four. In contrast, in focal area of virus-infected lungs, increasing numbers of phagocytic cells showed clumps of more than 25 bacteria/cell. These data demonstrate that virus-infected suppression of pulmonary antibacterial activity against S. aureus is related primarily to defects in intracellular processing mechanisms."} {"id": "PMID:180055", "title": "Interaction of prostaglandins and histamine with enzymes of cyclic AMP metabolism from guinea pig gastric mucosa.", "content": "Prostaglandins (PGE1, PGE2, PGA1) and histamine have opposing effects on gastric HCl secretion, but we found that both stimulate adenylate cyclase activity in cell-free membrane preparations of guinea pig gastric fundic mucosa. The stimulatory effect of prostaglandins was found in this study to be specific and dose-dependent over a concentration range from 10(-7) to 10(-4) M. In similar preparations from antral regions of guinea pig gastric mucosa, the adenylate cyclase was stimulated only by PGE1, PGE2, and PGA1 and not by histamine. Maximum stimulating doses of PGE1, PGE2, or PGA1, and of histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. Metiamide, a histamine H2-receptor antagonist, inhibited the stimulation of fundic mucosa adenylate cyclase by histamine but did not interfere with the stimulation by prostaglandins. Cyclic AMP phosphodiesterase activity of guinea pig gastric mucosa was unaffected by PGE1 and PGE2 or by histamine, and was slightly depressed by PGA1. These results indicate that histamine and prostaglandins stimulate two different adenylate cyclase systems both present in guinea pig gastric mucosa tissue. Therefore, the known inhibitory effect of prostaglandins on gastric acid secretion is not related to the interference with the stimulation of the histamine H2-receptor-sensitive adenylate cyclase complex by histamine nor do prostaglandins accelerate cyclic AMP breakdown by cyclic AMP phosphodiesterase to reduce cyclic AMP levels.", "contents": "Interaction of prostaglandins and histamine with enzymes of cyclic AMP metabolism from guinea pig gastric mucosa. Prostaglandins (PGE1, PGE2, PGA1) and histamine have opposing effects on gastric HCl secretion, but we found that both stimulate adenylate cyclase activity in cell-free membrane preparations of guinea pig gastric fundic mucosa. The stimulatory effect of prostaglandins was found in this study to be specific and dose-dependent over a concentration range from 10(-7) to 10(-4) M. In similar preparations from antral regions of guinea pig gastric mucosa, the adenylate cyclase was stimulated only by PGE1, PGE2, and PGA1 and not by histamine. Maximum stimulating doses of PGE1, PGE2, or PGA1, and of histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. Metiamide, a histamine H2-receptor antagonist, inhibited the stimulation of fundic mucosa adenylate cyclase by histamine but did not interfere with the stimulation by prostaglandins. Cyclic AMP phosphodiesterase activity of guinea pig gastric mucosa was unaffected by PGE1 and PGE2 or by histamine, and was slightly depressed by PGA1. These results indicate that histamine and prostaglandins stimulate two different adenylate cyclase systems both present in guinea pig gastric mucosa tissue. Therefore, the known inhibitory effect of prostaglandins on gastric acid secretion is not related to the interference with the stimulation of the histamine H2-receptor-sensitive adenylate cyclase complex by histamine nor do prostaglandins accelerate cyclic AMP breakdown by cyclic AMP phosphodiesterase to reduce cyclic AMP levels."} {"id": "PMID:180056", "title": "The renin-angiotensin-aldosterone system in congestive failure in conscious dogs.", "content": "The role of the renin-angiotensin-aldosterone system in the development of congestive failure has been assessed in the conscious dog by use of the nonapeptide converting enzyme inhibitor. Constriction of the pulmonary artery or thoracic inferior vena cava was maintained for 2 wk while daily measurements were made of plasma renin activity, plasma aldosterone, plasma volume, hematocrit, serum sodium and potassium concentrations, sodium and water balance, body weight, and arterial, caval, and atrial pressures. The initial response to constriction was a reduction in blood pressure, a rise in plasma renin activity, plasma aldosterone, and water intake, and nearly complete sodium retention. In the days after moderate constriction plasma volume and body weight increased (with development of ascites and edema); blood pressure, sodium excretion, plasma renin acvitity, and plasma aldosterone returned to normal. In animals in which blood pressure was not restored, plasma renin activity and plasma aldosterone remained elevated throughout the period of constriction. Single injections of converting enzyme inhibitor reduced blood pressure when plasma renin activity was elevated. Chronic infusion of the inhibitor in dogs with thoracic inferior vena caval constriction prevented the restoration of blood pressure and suppressed the rise in plasma aldosterone; sodium retention and volume expansion were less than in control experiments. Thus the renin-angiotensin-aldosterone system plays an essential role in the maintenance of blood pressure during the genesis of congestive failure. Initially, the restoration of blood pressure is dependent upon circulating angiotensin II; in the later stages, blood pressure is dependent upon the increase in plasma volume.", "contents": "The renin-angiotensin-aldosterone system in congestive failure in conscious dogs. The role of the renin-angiotensin-aldosterone system in the development of congestive failure has been assessed in the conscious dog by use of the nonapeptide converting enzyme inhibitor. Constriction of the pulmonary artery or thoracic inferior vena cava was maintained for 2 wk while daily measurements were made of plasma renin activity, plasma aldosterone, plasma volume, hematocrit, serum sodium and potassium concentrations, sodium and water balance, body weight, and arterial, caval, and atrial pressures. The initial response to constriction was a reduction in blood pressure, a rise in plasma renin activity, plasma aldosterone, and water intake, and nearly complete sodium retention. In the days after moderate constriction plasma volume and body weight increased (with development of ascites and edema); blood pressure, sodium excretion, plasma renin acvitity, and plasma aldosterone returned to normal. In animals in which blood pressure was not restored, plasma renin activity and plasma aldosterone remained elevated throughout the period of constriction. Single injections of converting enzyme inhibitor reduced blood pressure when plasma renin activity was elevated. Chronic infusion of the inhibitor in dogs with thoracic inferior vena caval constriction prevented the restoration of blood pressure and suppressed the rise in plasma aldosterone; sodium retention and volume expansion were less than in control experiments. Thus the renin-angiotensin-aldosterone system plays an essential role in the maintenance of blood pressure during the genesis of congestive failure. Initially, the restoration of blood pressure is dependent upon circulating angiotensin II; in the later stages, blood pressure is dependent upon the increase in plasma volume."} {"id": "PMID:180057", "title": "Effect of salicylates on histamine and L-histidine metabolism. Inhibition of imidazoleacetate phosphoribosyl transferase.", "content": "In man and other animals, urinary excretion of the histidine and histamine metabolite, imidazoleacetate, is increased and that of its conjugated metabolite, ribosylimidazoleacetate, decreased by salicylates. Imidazoleacetate has been reported to produce analgesia and narcosis. Its accumulation as a result of transferase inhibition could play a part in the therapeutic effects of salicylates. To determine the locus of salicylate action, we have investigated the effect of anti-inflammatory drugs on imidazoleacetate phosphoribosyl transferase, the enzyme that catalyzes the ATP-dependent conjugation of imidazoleacetate with phosphoribosylpyrophosphate. As little as 0.2 mM aspirin produced 50% inhibition of the rat liver transferase. In vivo, a 30% decrease in the urinary excretion of ribosylimidazoleacetate has been observed with plasma salicylate concentrations of 0.4 mM. The enzyme was also inhibited by sodium salicylate but not by salicylamide, sodium gentisate, aminopyrine, phenacetin, phenylbutazone, or indomethacin. The last four drugs have been shown previously not to alter the excretion of ribosylimidazoleacetate when administered in vivo. Since both the drug specificity and inhibitory concentrations are similar in vivo and in vitro, it seems probable that the effect of salicylates on imidazoleacetate conjugation results from inhibition of imidazoleacetate phosphoribosyl transferase.", "contents": "Effect of salicylates on histamine and L-histidine metabolism. Inhibition of imidazoleacetate phosphoribosyl transferase. In man and other animals, urinary excretion of the histidine and histamine metabolite, imidazoleacetate, is increased and that of its conjugated metabolite, ribosylimidazoleacetate, decreased by salicylates. Imidazoleacetate has been reported to produce analgesia and narcosis. Its accumulation as a result of transferase inhibition could play a part in the therapeutic effects of salicylates. To determine the locus of salicylate action, we have investigated the effect of anti-inflammatory drugs on imidazoleacetate phosphoribosyl transferase, the enzyme that catalyzes the ATP-dependent conjugation of imidazoleacetate with phosphoribosylpyrophosphate. As little as 0.2 mM aspirin produced 50% inhibition of the rat liver transferase. In vivo, a 30% decrease in the urinary excretion of ribosylimidazoleacetate has been observed with plasma salicylate concentrations of 0.4 mM. The enzyme was also inhibited by sodium salicylate but not by salicylamide, sodium gentisate, aminopyrine, phenacetin, phenylbutazone, or indomethacin. The last four drugs have been shown previously not to alter the excretion of ribosylimidazoleacetate when administered in vivo. Since both the drug specificity and inhibitory concentrations are similar in vivo and in vitro, it seems probable that the effect of salicylates on imidazoleacetate conjugation results from inhibition of imidazoleacetate phosphoribosyl transferase."} {"id": "PMID:180058", "title": "Exaggerated phosphaturic response to circulating parathyroid hormone in patients with familial X-linked hypophosphatemic rickets.", "content": "To determine whether the phosphaturic response to circulating parathyroid hormone (PTH) is exaggerated in patients with familial x-linked hypophosphatemic vitamin D-resistant rickets (FHR), we examined the phosphaturic response to parathyroid extract (PTE) (administered intravenously in the posthypercalcemic state) in two unrelated adult hemizygotes with FHR. In these two patients whose plasma concentration of PTH was normal (determined by radioimmunoassay). neither vitamin D nor phosphate therapy had been given during the past 10 yr. Two normal men and a hypophosphatemic man with intestinal malabsorption, hypocalcemia, and osteomalacia served as control subjects. In all subjects, calcium gluconate was adminstered intravenously from 6 p.m. to 12 midnight at a rate that maintained the concentration of serum calcium at 13-15 mg/100 ml during the administration of calcium. When normocalcemia had recurred the next morning, and the plasma PTH concentration and urinary excretion of cyclic 3', 5'-AMP were reduced. PTE was administered intravenously at successively increasing rates of 0.1, 0.4, and 0.8 U/kg per h, each rate lasting 90 min. Minutes after the initiation of PTE in the affected hemizygotes, fractional excretion of filtered phosphate increased from negligible values to values strikingly greater than those of similarly studied control subjects and plateaued at strikingly greater values throughout further administration of PTE. This phenomenon of exaggerated phosphaturia could not be attributed to volume expansion, decreases in serum concentration of calcium during the study, differences in percent of administered calcium retained, or hemodynamic changes. Only the phosphaturic response to PTE appeared to be exaggerated. At any cumulative dose of PTE, urinary excretion of cyclic 3', 5'-AMP in the hemizogytes was indistinguishable from that of control subjects. The findings in this study suggest that in patients with FHR, circulating PTH is required for the genetically transmitted abnormality to be physiologically expressed as a reduction in net renal reabsorption of phosphate, and that this physiological expression of the genetic abnormality is expressed fully at normal or nearly normal circulating levels of PTH.", "contents": "Exaggerated phosphaturic response to circulating parathyroid hormone in patients with familial X-linked hypophosphatemic rickets. To determine whether the phosphaturic response to circulating parathyroid hormone (PTH) is exaggerated in patients with familial x-linked hypophosphatemic vitamin D-resistant rickets (FHR), we examined the phosphaturic response to parathyroid extract (PTE) (administered intravenously in the posthypercalcemic state) in two unrelated adult hemizygotes with FHR. In these two patients whose plasma concentration of PTH was normal (determined by radioimmunoassay). neither vitamin D nor phosphate therapy had been given during the past 10 yr. Two normal men and a hypophosphatemic man with intestinal malabsorption, hypocalcemia, and osteomalacia served as control subjects. In all subjects, calcium gluconate was adminstered intravenously from 6 p.m. to 12 midnight at a rate that maintained the concentration of serum calcium at 13-15 mg/100 ml during the administration of calcium. When normocalcemia had recurred the next morning, and the plasma PTH concentration and urinary excretion of cyclic 3', 5'-AMP were reduced. PTE was administered intravenously at successively increasing rates of 0.1, 0.4, and 0.8 U/kg per h, each rate lasting 90 min. Minutes after the initiation of PTE in the affected hemizygotes, fractional excretion of filtered phosphate increased from negligible values to values strikingly greater than those of similarly studied control subjects and plateaued at strikingly greater values throughout further administration of PTE. This phenomenon of exaggerated phosphaturia could not be attributed to volume expansion, decreases in serum concentration of calcium during the study, differences in percent of administered calcium retained, or hemodynamic changes. Only the phosphaturic response to PTE appeared to be exaggerated. At any cumulative dose of PTE, urinary excretion of cyclic 3', 5'-AMP in the hemizogytes was indistinguishable from that of control subjects. The findings in this study suggest that in patients with FHR, circulating PTH is required for the genetically transmitted abnormality to be physiologically expressed as a reduction in net renal reabsorption of phosphate, and that this physiological expression of the genetic abnormality is expressed fully at normal or nearly normal circulating levels of PTH."} {"id": "PMID:180059", "title": "The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.", "content": "18-hydroxy 11-deoxycorticosterone (18-OH DOC), a weak mineralocorticoid, was estimated by a radioimmunoassay procedure after purification in 49 patients with hypertension and 38 normal control subjects. The sensitivity of the method was 2-4 pg; there was no detectable blank, and the precision was 9-10%. In normal subjects the absolute plasma levels were similar to those of aldosterone. ACTH administration produced a 23-fold increase, and sodium restriction resulted in a 4-fold increase (5.4+/-0.7-20.5+/-3.0 ng/dl). On the other hand, the plasma levels of 18-OH DOC declined by nearly 50% with upright posture or angiotensin II infusion. During both of these procedures, plasma aldosterone levels significantly increased. Patients with normal and low renin hypertension had similar changes in plasma 18-OH DOC levels with sodium restriction. However, the mean high sodium level in the normal renin essential hypertension group (11.6+/-1.6 ng/dl) was significantly greater (P is less than 0.001) than in the control group (5.4+/-0.7 ng/dl). In addition, at least 22% and perhaps as high as 37% of the hypertensive subjects had levels greater than the upper limits of normal on a high sodium intake. Differences between the groups were less impressive in the sodium-restricted studies. There were no significant differences in age, duration of hypertension, sodium balance, serum sodium, potassium, or blood urea nitrogen in those patients who had elevated levels of plasma 18-OH DOC. Patients with primary aldosteronism had levels within the normal range on both dietary intake. However, in contrast to the other groups there were no significant changes in the plasma levels with sodium restriction. Thus, a significant number of patients with essential hypertension presumably have an alteration in 18-OH DOC secretion.", "contents": "The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man. 18-hydroxy 11-deoxycorticosterone (18-OH DOC), a weak mineralocorticoid, was estimated by a radioimmunoassay procedure after purification in 49 patients with hypertension and 38 normal control subjects. The sensitivity of the method was 2-4 pg; there was no detectable blank, and the precision was 9-10%. In normal subjects the absolute plasma levels were similar to those of aldosterone. ACTH administration produced a 23-fold increase, and sodium restriction resulted in a 4-fold increase (5.4+/-0.7-20.5+/-3.0 ng/dl). On the other hand, the plasma levels of 18-OH DOC declined by nearly 50% with upright posture or angiotensin II infusion. During both of these procedures, plasma aldosterone levels significantly increased. Patients with normal and low renin hypertension had similar changes in plasma 18-OH DOC levels with sodium restriction. However, the mean high sodium level in the normal renin essential hypertension group (11.6+/-1.6 ng/dl) was significantly greater (P is less than 0.001) than in the control group (5.4+/-0.7 ng/dl). In addition, at least 22% and perhaps as high as 37% of the hypertensive subjects had levels greater than the upper limits of normal on a high sodium intake. Differences between the groups were less impressive in the sodium-restricted studies. There were no significant differences in age, duration of hypertension, sodium balance, serum sodium, potassium, or blood urea nitrogen in those patients who had elevated levels of plasma 18-OH DOC. Patients with primary aldosteronism had levels within the normal range on both dietary intake. However, in contrast to the other groups there were no significant changes in the plasma levels with sodium restriction. Thus, a significant number of patients with essential hypertension presumably have an alteration in 18-OH DOC secretion."} {"id": "PMID:180060", "title": "Chemiluminescence and superoxide production by myeloperoxidase-deficient leukocytes.", "content": "The role of superoxide anion- and myeloperoxidase-dependent reactions in the light emission by phagocytosing polymorphonuclear leukocytes has been investigated using leukocytes that lack myeloperoxidase, inhibitors (azide, superoxide dismutase), and model systems. Our earlier finding that oxygen consumption, glucose C-1 oxidation, and formate oxidation are greater in polymorphonuclear leukocytes that lack myeloperoxidase than in normal cells during phagocytosis has been confirmed with leukocytes from two newly described myeloperoxidase-deficient siblings. Although the maximal rate of superoxide anion production by myeloperoxidase-deficient leukocytes is not significantly different from that of normal cells, superoxide production falls off less rapidly with time so that with prolonged incubation, it is greater in myeloperoxidase-deficient than in normal cells. Chemiluminescence by myeloperoxidase-deficient leukocytes during the early postphagocytic period however is decreased. Light emission by normal leukocytes is strongly inhibited by both superoxide dismutase and azide, whereas that of myeloperoxidase-deficient leukocytes, while still strongly inhibited by superoxide dismutase is considerably less sensitive to azide. Zymosan, the phagocytic particle employed in the intact cell system, considerably increased the chemiluminescence of a cell-free superoxide-H2O2 generating system (xanthine-xanthine oxidase) and a system containing myeloperoxidase, H2O2, and chloride. Light emission by the xanthine oxidase model system is strongly inhibited by superoxide dismutase and is not inhibited by azide, whereas the myeloperoxidase-dependent model system is strongly inhibited by azide but only slightly inhibited by superoxide dismutase. These findings suggest that light emission by phagocytosing polymorphonuclear leukocytes is dependent on both myeloperoxidase-catalyzed reactions and the superoxide anion, and involves in part the excitation of the ingested particle. These studies are discussed in relation to the role of the superoxide anion and chemiluminescence in the microbicidal activity of the polymorphonuclear leukocyte.", "contents": "Chemiluminescence and superoxide production by myeloperoxidase-deficient leukocytes. The role of superoxide anion- and myeloperoxidase-dependent reactions in the light emission by phagocytosing polymorphonuclear leukocytes has been investigated using leukocytes that lack myeloperoxidase, inhibitors (azide, superoxide dismutase), and model systems. Our earlier finding that oxygen consumption, glucose C-1 oxidation, and formate oxidation are greater in polymorphonuclear leukocytes that lack myeloperoxidase than in normal cells during phagocytosis has been confirmed with leukocytes from two newly described myeloperoxidase-deficient siblings. Although the maximal rate of superoxide anion production by myeloperoxidase-deficient leukocytes is not significantly different from that of normal cells, superoxide production falls off less rapidly with time so that with prolonged incubation, it is greater in myeloperoxidase-deficient than in normal cells. Chemiluminescence by myeloperoxidase-deficient leukocytes during the early postphagocytic period however is decreased. Light emission by normal leukocytes is strongly inhibited by both superoxide dismutase and azide, whereas that of myeloperoxidase-deficient leukocytes, while still strongly inhibited by superoxide dismutase is considerably less sensitive to azide. Zymosan, the phagocytic particle employed in the intact cell system, considerably increased the chemiluminescence of a cell-free superoxide-H2O2 generating system (xanthine-xanthine oxidase) and a system containing myeloperoxidase, H2O2, and chloride. Light emission by the xanthine oxidase model system is strongly inhibited by superoxide dismutase and is not inhibited by azide, whereas the myeloperoxidase-dependent model system is strongly inhibited by azide but only slightly inhibited by superoxide dismutase. These findings suggest that light emission by phagocytosing polymorphonuclear leukocytes is dependent on both myeloperoxidase-catalyzed reactions and the superoxide anion, and involves in part the excitation of the ingested particle. These studies are discussed in relation to the role of the superoxide anion and chemiluminescence in the microbicidal activity of the polymorphonuclear leukocyte."} {"id": "PMID:180061", "title": "Fluorescent antibody responses to adenoviruses in humans.", "content": "Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, \"T\" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of \"T\" antibody study in diagnosis.", "contents": "Fluorescent antibody responses to adenoviruses in humans. Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, \"T\" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of \"T\" antibody study in diagnosis."} {"id": "PMID:180062", "title": "Serum beta-lipoprotein and other specific protein concentrations in patients with immunocytoma.", "content": "Serum beta-lipoprotein and other specific protein concentrations were measured in 56 patients suffering from multiple myelomatosis, \"benign\" paraproteinaemia or Waldenstr\u00f6m's macroglobulinaemia and in 56 control subjects. The mean level of B-lipoprotein in untreated patients with multiple myelomatosis and macroglobulinaemia was significantly lower than that of the controls. Patients who responded to chemotherapy showed a rapid return to normal of the beta-lipoprotein concentration, while the level remained unchanged in most of those who did not.", "contents": "Serum beta-lipoprotein and other specific protein concentrations in patients with immunocytoma. Serum beta-lipoprotein and other specific protein concentrations were measured in 56 patients suffering from multiple myelomatosis, \"benign\" paraproteinaemia or Waldenstr\u00f6m's macroglobulinaemia and in 56 control subjects. The mean level of B-lipoprotein in untreated patients with multiple myelomatosis and macroglobulinaemia was significantly lower than that of the controls. Patients who responded to chemotherapy showed a rapid return to normal of the beta-lipoprotein concentration, while the level remained unchanged in most of those who did not."} {"id": "PMID:180063", "title": "Membrane activity in histiocytic diseases of the skin.", "content": "Study of the histiocytes from a large variety of skin diseases demonstrates a close relationship between the cell processes peculiar to those cells and their degree of phagocytic activity. The membrane structures, as well as the dense bodies localized in the peripheral cytoplasm, suggest a type of endocytosis distinct from pinocytosis and phagocytosis.", "contents": "Membrane activity in histiocytic diseases of the skin. Study of the histiocytes from a large variety of skin diseases demonstrates a close relationship between the cell processes peculiar to those cells and their degree of phagocytic activity. The membrane structures, as well as the dense bodies localized in the peripheral cytoplasm, suggest a type of endocytosis distinct from pinocytosis and phagocytosis."} {"id": "PMID:180064", "title": "Regulation of bacterial motility by cyclic nucleotides and effect of biogenic amines.", "content": "When assayed by a newly devised, simple and quantitative method, \"motilometry\", the motility of E. coli S-26 was found stimulated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) and 8-hydroxy cyclic AMP as well as histamine, catecholamines and inhibited by cyclic guanosine 3':5'-monophosphate (cyclic GMP). The stimulation elicited by cyclic AMP or other biogenic amines was reversed by cyclic GMP. The experimental significance and implicaton of these findings are discussed.", "contents": "Regulation of bacterial motility by cyclic nucleotides and effect of biogenic amines. When assayed by a newly devised, simple and quantitative method, \"motilometry\", the motility of E. coli S-26 was found stimulated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) and 8-hydroxy cyclic AMP as well as histamine, catecholamines and inhibited by cyclic guanosine 3':5'-monophosphate (cyclic GMP). The stimulation elicited by cyclic AMP or other biogenic amines was reversed by cyclic GMP. The experimental significance and implicaton of these findings are discussed."} {"id": "PMID:180065", "title": "Activation of cyclic AMP phosphodiesterase by a new vitamin E derivative.", "content": "The effects of sodium alpha-tocopherol phosphate (TPNa), a new vitamin E derivative, on cyclic nucleotide phosphodiesterases from a soluble supernatant fraction of rat liver were investigated. TPNa produced a dose-dependent increase in cyclic AMP hydrolysis at a low substrate concentration (1 muM cyclic AMP), whereas the compound inhibited the hydrolytic activity at a high substrate level (100 muM cyclic AMP). Cyclic GMP phosphodiesterase activity was suppressed by TPNa regardless of the substrate concentration. The addition of TPNa did not change the apparent Km value (50 muM) of cyclic AMP phosphodiesterase at low substrate level (less than 5 muM). In contrast, at higher substrate concentration, the concave downward curve observed in a Lineweaver-Burk plot became straight in the presence of TPNa. Low concentrations of cyclic GMP, which are known to activate cyclic AMP hydrolysis, showed an additive effect on cyclic AMP phosphodiesterase only when a submaximal concentration of cyclic GMP was present in addition to TPNa. These and other data suggest that TPNa modifies cyclic AMP phosphodiesterase in all allosteric fashion.", "contents": "Activation of cyclic AMP phosphodiesterase by a new vitamin E derivative. The effects of sodium alpha-tocopherol phosphate (TPNa), a new vitamin E derivative, on cyclic nucleotide phosphodiesterases from a soluble supernatant fraction of rat liver were investigated. TPNa produced a dose-dependent increase in cyclic AMP hydrolysis at a low substrate concentration (1 muM cyclic AMP), whereas the compound inhibited the hydrolytic activity at a high substrate level (100 muM cyclic AMP). Cyclic GMP phosphodiesterase activity was suppressed by TPNa regardless of the substrate concentration. The addition of TPNa did not change the apparent Km value (50 muM) of cyclic AMP phosphodiesterase at low substrate level (less than 5 muM). In contrast, at higher substrate concentration, the concave downward curve observed in a Lineweaver-Burk plot became straight in the presence of TPNa. Low concentrations of cyclic GMP, which are known to activate cyclic AMP hydrolysis, showed an additive effect on cyclic AMP phosphodiesterase only when a submaximal concentration of cyclic GMP was present in addition to TPNa. These and other data suggest that TPNa modifies cyclic AMP phosphodiesterase in all allosteric fashion."} {"id": "PMID:180066", "title": "Effect of acetylcholine on glycogen phosphorylase activity and cyclic nucleotide content in isolated perfused rat hearts.", "content": "Acetylcholine (1muM) increased cyclid GMP content in paced perfused rat hearts within 15 sec., with peak content occurring at 1 min. No effect of acetylcholine on cyclic AMP content, phosphorylase activity or glycogen synthase was observed. Epinephrine (1muM) infusion increased both cyclic AMP content and phosphorylase, but did not alter cyclic GMP content or glycogen synthase activity. When acetylcholine was infused during the second min. of a 2 min. infusion of epinephrine, the cholinergic agent increased cyclic GMP and reduced the stimulated phosphorylase activity and elevated cyclic AMP.", "contents": "Effect of acetylcholine on glycogen phosphorylase activity and cyclic nucleotide content in isolated perfused rat hearts. Acetylcholine (1muM) increased cyclid GMP content in paced perfused rat hearts within 15 sec., with peak content occurring at 1 min. No effect of acetylcholine on cyclic AMP content, phosphorylase activity or glycogen synthase was observed. Epinephrine (1muM) infusion increased both cyclic AMP content and phosphorylase, but did not alter cyclic GMP content or glycogen synthase activity. When acetylcholine was infused during the second min. of a 2 min. infusion of epinephrine, the cholinergic agent increased cyclic GMP and reduced the stimulated phosphorylase activity and elevated cyclic AMP."} {"id": "PMID:180067", "title": "Cyclic nucleotide levels during carbachol-induced smooth muscle contractions.", "content": "Cyclic nucleotide levels and tension were measured at various times during carbachol-induced smooth muscle contractions. Cyclic GMP levels were markedly increased during contractions of rat vas deferens, guinea pig myometrium and guinea pig taenia coli, but were unchanged during contractions of rat uterus or guinea pig ileum. No significant changes in cyclic GMP levels could be detected in estrogen-primed rat uteri at any of the times or drug concentrations studied. Even in tissues in which large increases in cyclic GMP levels could be detected during carbachol-induced contractions (i.e. guinea pig myometrium and taenia coli) the contractions appeared to precede the cyclic GMP increases by several seconds. No significant changes in cyclic AMP levels were observed during carbachol-induced contractions in any of the smooth muscles studied. Thus, changes in tissue levels of the cyclic nucleotides do not appear to be responsible for the initiation of carbachol-induced smooth muscle contractions.", "contents": "Cyclic nucleotide levels during carbachol-induced smooth muscle contractions. Cyclic nucleotide levels and tension were measured at various times during carbachol-induced smooth muscle contractions. Cyclic GMP levels were markedly increased during contractions of rat vas deferens, guinea pig myometrium and guinea pig taenia coli, but were unchanged during contractions of rat uterus or guinea pig ileum. No significant changes in cyclic GMP levels could be detected in estrogen-primed rat uteri at any of the times or drug concentrations studied. Even in tissues in which large increases in cyclic GMP levels could be detected during carbachol-induced contractions (i.e. guinea pig myometrium and taenia coli) the contractions appeared to precede the cyclic GMP increases by several seconds. No significant changes in cyclic AMP levels were observed during carbachol-induced contractions in any of the smooth muscles studied. Thus, changes in tissue levels of the cyclic nucleotides do not appear to be responsible for the initiation of carbachol-induced smooth muscle contractions."} {"id": "PMID:180072", "title": "Bronchiolitis and asthma: possible common pathogenetic pathways.", "content": "A discussion of possible mechanism for virus-induced wheezing in normal and asthmatic children is presented. Presently attractive theories for immune injury in viral bronchiolitis include those which depend on pathology induced by types 1, 3, and 4 of Gell and Coombs. The continuum of viral bronchiolitis with virus-induced wheezing in young children who are labeled \"asthmatic\" argues for some common mechanism of bronchiolar obstruction.", "contents": "Bronchiolitis and asthma: possible common pathogenetic pathways. A discussion of possible mechanism for virus-induced wheezing in normal and asthmatic children is presented. Presently attractive theories for immune injury in viral bronchiolitis include those which depend on pathology induced by types 1, 3, and 4 of Gell and Coombs. The continuum of viral bronchiolitis with virus-induced wheezing in young children who are labeled \"asthmatic\" argues for some common mechanism of bronchiolar obstruction."} {"id": "PMID:180069", "title": "Study of the arrangement of crystallites in gamma-irradiated human enamel by electron paramagnetic resonance.", "content": "The arrangement of tooth enamel microcrystals has been studied on CO3-3 bound electrons by electron paramagnetic resonance. It was found that noncarious human maxillary central incisors have a greater degree of alignment of tooth enamel microcrystals than the carious ones. The outermost surface layer of enamel showed a greater crystallite degree of alignment than other parts.", "contents": "Study of the arrangement of crystallites in gamma-irradiated human enamel by electron paramagnetic resonance. The arrangement of tooth enamel microcrystals has been studied on CO3-3 bound electrons by electron paramagnetic resonance. It was found that noncarious human maxillary central incisors have a greater degree of alignment of tooth enamel microcrystals than the carious ones. The outermost surface layer of enamel showed a greater crystallite degree of alignment than other parts."} {"id": "PMID:180087", "title": "[Effects of methotrexate on cervico-vaginal cytology].", "content": "Disturbances of folic acid metabolism can bring about the appearance of characteristic displastic cells, FD cells, in the cervico-vaginal epithelium. A study of the colpocytogram in a series of patients who had trophoblastic tumours treated with methotrexate shows that the administration of an antifolic agent can provoke under certain conditions the appearance of FD cells or an increase in their number when they are present before chemotherapy has been started. These cells are in a variable percentage of cases, transitory in nature but when methotrexate treatments are repeated they often return as a regular feature. The cytomorphologic aspect of these FD cells when they appear after chemotherapy is identical to those that exist spontaneously in certain deficiency conditions occuring in pregnancy and the puerperium.", "contents": "[Effects of methotrexate on cervico-vaginal cytology]. Disturbances of folic acid metabolism can bring about the appearance of characteristic displastic cells, FD cells, in the cervico-vaginal epithelium. A study of the colpocytogram in a series of patients who had trophoblastic tumours treated with methotrexate shows that the administration of an antifolic agent can provoke under certain conditions the appearance of FD cells or an increase in their number when they are present before chemotherapy has been started. These cells are in a variable percentage of cases, transitory in nature but when methotrexate treatments are repeated they often return as a regular feature. The cytomorphologic aspect of these FD cells when they appear after chemotherapy is identical to those that exist spontaneously in certain deficiency conditions occuring in pregnancy and the puerperium."} {"id": "PMID:180174", "title": "Cytochemical model system for microsomal rat liver glucose-6-phosphate.", "content": "A method is described for the incorporation of a microsomal rat liver fraction into polyacrylamide films without significant loss of its glucose-6-phosphatase activity. The enzymatic activity was completely lost when the films were prepared with ammonium persulfate as initiator of the polymerization as previously described for alkaline phosphatase, but modification of this method showed that about 90% of the glucose-6-phosphatase activity could be retained. The enzyme in the films prepared with the new method was completely inhibited by alloxan, HgCl2, and preincubation in 0.05 M acetate buffer (pH 5.0) at 37 degrees C, as determined biochemically. Similar results were obtained for the enzyme in films determined histochemically according to the lead method of Wachstein and Meisel. In this respect the behavior of the incorporated enzyme is similar to that in suspension. Films fixed with 1.5% glutaraldehyde showed rapid inactivation of glucose-6-phosphatase. There was good correlation between the biochemical and histochemical activity determined after fixation. A method to embed polyacrylamide films in Epon for electron-microscopical investigation is also described. Dimethyl sulfoxide was used as the dehydrating agent instead of ethanol/acetone.", "contents": "Cytochemical model system for microsomal rat liver glucose-6-phosphate. A method is described for the incorporation of a microsomal rat liver fraction into polyacrylamide films without significant loss of its glucose-6-phosphatase activity. The enzymatic activity was completely lost when the films were prepared with ammonium persulfate as initiator of the polymerization as previously described for alkaline phosphatase, but modification of this method showed that about 90% of the glucose-6-phosphatase activity could be retained. The enzyme in the films prepared with the new method was completely inhibited by alloxan, HgCl2, and preincubation in 0.05 M acetate buffer (pH 5.0) at 37 degrees C, as determined biochemically. Similar results were obtained for the enzyme in films determined histochemically according to the lead method of Wachstein and Meisel. In this respect the behavior of the incorporated enzyme is similar to that in suspension. Films fixed with 1.5% glutaraldehyde showed rapid inactivation of glucose-6-phosphatase. There was good correlation between the biochemical and histochemical activity determined after fixation. A method to embed polyacrylamide films in Epon for electron-microscopical investigation is also described. Dimethyl sulfoxide was used as the dehydrating agent instead of ethanol/acetone."} {"id": "PMID:180175", "title": "Studies of experimental rhinovirus type 2 infections in polar isolation and in England.", "content": "After five months of total isolation a wintering party of seventeen British Antarctic Survey (BAS) personnel was inoculated under double blind concitions with placebo, or rhinovirus type 2 which had been propagated in tissue culture. The clinical and virological responses of these subjects were compared with those of volunteers in England who received a similar dose of the same strain. The virus used was apparently partly attenuated for man; at the dosage used its effects in England were similar to a smaller dose of an unattenuated strain, but in the Antarctic it caused relatively severe infections. Both the symptoms and the laboratory evidence of virus infection appeared to be more pronounced in the BAS subjects than in the volunteers in England who received the same challenge. In the former group the infection readily spread to those who were originally given placebo. In the BAS subjects serum antibody titres were well maintained during the isolation period but a significant fall in nasal immunoglobulin concentration was recorded during the 5 months of isolation after the virus challenge. Possible mechanisms for the increased sensitivity to rhinovirus of subjects who have been totally isolated in a small closed community are discussed.", "contents": "Studies of experimental rhinovirus type 2 infections in polar isolation and in England. After five months of total isolation a wintering party of seventeen British Antarctic Survey (BAS) personnel was inoculated under double blind concitions with placebo, or rhinovirus type 2 which had been propagated in tissue culture. The clinical and virological responses of these subjects were compared with those of volunteers in England who received a similar dose of the same strain. The virus used was apparently partly attenuated for man; at the dosage used its effects in England were similar to a smaller dose of an unattenuated strain, but in the Antarctic it caused relatively severe infections. Both the symptoms and the laboratory evidence of virus infection appeared to be more pronounced in the BAS subjects than in the volunteers in England who received the same challenge. In the former group the infection readily spread to those who were originally given placebo. In the BAS subjects serum antibody titres were well maintained during the isolation period but a significant fall in nasal immunoglobulin concentration was recorded during the 5 months of isolation after the virus challenge. Possible mechanisms for the increased sensitivity to rhinovirus of subjects who have been totally isolated in a small closed community are discussed."} {"id": "PMID:180176", "title": "The role of sheep and goats in the epizootiology of foot-and-mouth disease in Kenya.", "content": "The pathogenicity of two bovine field strains of virus for indigenous goats was examined in the laboratory. The goats failed to develop clinical disease or become virus carriers although the majority showed a definite immune response. A field survey in a foot-and-mouth disease enzootic area showed that the indigenous sheep and goat populations were frequently exposed to infection as evidenced by a high proportion of sero-positive animals but the incidence of virus carriers was very low in goats and no carriers were detected in sheep.", "contents": "The role of sheep and goats in the epizootiology of foot-and-mouth disease in Kenya. The pathogenicity of two bovine field strains of virus for indigenous goats was examined in the laboratory. The goats failed to develop clinical disease or become virus carriers although the majority showed a definite immune response. A field survey in a foot-and-mouth disease enzootic area showed that the indigenous sheep and goat populations were frequently exposed to infection as evidenced by a high proportion of sero-positive animals but the incidence of virus carriers was very low in goats and no carriers were detected in sheep."} {"id": "PMID:180177", "title": "Growth of foot-and-mouth disease virus in the upper respiratory tract of non-immunized, vaccinated, and recovered cattle after intranasal inoculation.", "content": "Non-immunized, vaccinated, and recovered cattle were inoculated intranasally with various doses of foot-and-mouth disease virus. Samples of oesophageal-pharyngeal (OP) fluid were taken periodically for up to 7 days after inoculation and virus titres of these samples were plotted as pharyngeal virus growth curves. In non-immunized cattle, the length of the lag period and of the growth period were inversely proportional to the dose of virus given. Maximum titres were observed when clinical signs were first detected. Three of the 10 cattle studied had virus growth rates that were lower than rates of others given the same dose of virus, and clinical signs appeared later than expected in these three cattle. Cattle vaccinated with an inactivated virus oil-adjuvant vaccine had pharyngeal virus growth curves that were similar to those obtained from non-immunized cattle for 30 h. after inoculation. Titres of virus in OP fluid samples taken 2-7 days after inoculation were substantially lower in cattle with a high pre-exposure serum mouse protection index than titres from partly-immunized or non-immunized cattle. Nine of 14 cattle had detectable but reduced virus growth after intranasal inoculation with homologous virus. Five recovered cattle inoculated with heterologous virus reacted similarly to non-immunized animals.", "contents": "Growth of foot-and-mouth disease virus in the upper respiratory tract of non-immunized, vaccinated, and recovered cattle after intranasal inoculation. Non-immunized, vaccinated, and recovered cattle were inoculated intranasally with various doses of foot-and-mouth disease virus. Samples of oesophageal-pharyngeal (OP) fluid were taken periodically for up to 7 days after inoculation and virus titres of these samples were plotted as pharyngeal virus growth curves. In non-immunized cattle, the length of the lag period and of the growth period were inversely proportional to the dose of virus given. Maximum titres were observed when clinical signs were first detected. Three of the 10 cattle studied had virus growth rates that were lower than rates of others given the same dose of virus, and clinical signs appeared later than expected in these three cattle. Cattle vaccinated with an inactivated virus oil-adjuvant vaccine had pharyngeal virus growth curves that were similar to those obtained from non-immunized cattle for 30 h. after inoculation. Titres of virus in OP fluid samples taken 2-7 days after inoculation were substantially lower in cattle with a high pre-exposure serum mouse protection index than titres from partly-immunized or non-immunized cattle. Nine of 14 cattle had detectable but reduced virus growth after intranasal inoculation with homologous virus. Five recovered cattle inoculated with heterologous virus reacted similarly to non-immunized animals."} {"id": "PMID:180178", "title": "Immunologic mechanisms in the pathogenesis of virus-induced murine leukemia. III. Target cell specificity of autoreactive thymocytes.", "content": "Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infected with nononcogenic lymphocytic choriomeningitis virus (LCMV), or transformed by the chemical carcinogen 3-methylcholanthrene were not similarly spared. This phenomenon, apparently induced by MuLV-M, is not associated with all persistent virus carrier states. Thymocytes from mice persistently infected with LCMV or with the lactic dehydrogenase virus (LDHV) failed to demonstrate an autoaggressive behavior. That transplantable lymphoma cells (derived from MuLV-M-carriers) were autoreactive in a pattern similar to thymocytes from preleukemic mice suggests a unique role for MuLV in the events leading from altered recognition of \"self\" to lymphoma.", "contents": "Immunologic mechanisms in the pathogenesis of virus-induced murine leukemia. III. Target cell specificity of autoreactive thymocytes. Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infected with nononcogenic lymphocytic choriomeningitis virus (LCMV), or transformed by the chemical carcinogen 3-methylcholanthrene were not similarly spared. This phenomenon, apparently induced by MuLV-M, is not associated with all persistent virus carrier states. Thymocytes from mice persistently infected with LCMV or with the lactic dehydrogenase virus (LDHV) failed to demonstrate an autoaggressive behavior. That transplantable lymphoma cells (derived from MuLV-M-carriers) were autoreactive in a pattern similar to thymocytes from preleukemic mice suggests a unique role for MuLV in the events leading from altered recognition of \"self\" to lymphoma."} {"id": "PMID:180179", "title": "Appearance of IgG (Fc) receptor(s) on cultured human fibroblasts infected with human cytomegalovirus.", "content": "Cultured human diploid fibroblasts (WI-38) after infection with human cytomegalovirus (CMV) but not when uninfected, could hemadsorb sheep red blood cells (SRBC) coated with rabbit anti-SRBC IgG. The adsorption of IgG-coated SRBC to virus-infected cells was completely abolished if the tests were carried out in the simultaneous presence of rabbit antiserum elicited against CMV. Normal sera of rabbit or human origin as well as purified human IgG but not Fab fragment of human IgG could also abolish the binding of sensitized SRBC to CMV-infected fibroblasts. Active metabolism on the part of CMV-infected fibroblasts proved to be an important requisite for demonstrating binding of sensitized SRBC to their surfaces. By using an indicator Staphylococcus aureus to which rabbit antiserum against normal human IgG, IgM, or IgA was bound via Fc fragments, evidence has been obtained which suggests the existence of receptor(s) on CMV-infected WI-38 cells that react specifically with Fc region of human IgG.", "contents": "Appearance of IgG (Fc) receptor(s) on cultured human fibroblasts infected with human cytomegalovirus. Cultured human diploid fibroblasts (WI-38) after infection with human cytomegalovirus (CMV) but not when uninfected, could hemadsorb sheep red blood cells (SRBC) coated with rabbit anti-SRBC IgG. The adsorption of IgG-coated SRBC to virus-infected cells was completely abolished if the tests were carried out in the simultaneous presence of rabbit antiserum elicited against CMV. Normal sera of rabbit or human origin as well as purified human IgG but not Fab fragment of human IgG could also abolish the binding of sensitized SRBC to CMV-infected fibroblasts. Active metabolism on the part of CMV-infected fibroblasts proved to be an important requisite for demonstrating binding of sensitized SRBC to their surfaces. By using an indicator Staphylococcus aureus to which rabbit antiserum against normal human IgG, IgM, or IgA was bound via Fc fragments, evidence has been obtained which suggests the existence of receptor(s) on CMV-infected WI-38 cells that react specifically with Fc region of human IgG."} {"id": "PMID:180181", "title": "Enhancement of early human E rosette formation by cholinergic stimuli.", "content": "The effects of the cholinergic stimuli carbamylcholine (carbachol) and dibutyrl cyclic guanosine monophosphate (DBCGMP) were determined on both 'early' and 'total' E rosette formation. Ficoll-Hypaque-separated lymphocytes were preincubated with either carbachol or DBCGMP over a 10(-3) M to 10(-13) M dose range. Both agents significantly enhanced 'early', but not 'total' E rosette formation. Peak enhancement above control values occurred at 10(-7) M (72%) and 10(-9) M (69%) for carbachol and 10(-5) M (70%) and 10(-7) M (70%) for DBCGMP. Kinetic studies showed a rapid onset of enhancement (2.5 min) for carbachol, whereas DBCGMP required 15 min for significant enhancement to occur. The muscurinic nature of carbachol enhancement of E rosettes was demonstrated. Atropine at 10(-7) M completely abolished the carbachol effect while showing little inhibition of the DBCGMP effect on rosette formation. These studies indicate that the cholinergic stimuli carbachl and DBCGMP significantly enhance the 'early' E rosette former in man. Human T lymphocytes appear to have functional cholinergic receptors that can be blocked by the muscurinic antagonist atropine. The role of the cyclic nucleotides and their stimulants on the immune system is incompletely understood, but it would appear that they are extremely important in the differentiation and function of the T lymphocyte. E rosette formation may be a useful model in man for studying the effects of the cyclic nucleotides on the human T lymphocyte.", "contents": "Enhancement of early human E rosette formation by cholinergic stimuli. The effects of the cholinergic stimuli carbamylcholine (carbachol) and dibutyrl cyclic guanosine monophosphate (DBCGMP) were determined on both 'early' and 'total' E rosette formation. Ficoll-Hypaque-separated lymphocytes were preincubated with either carbachol or DBCGMP over a 10(-3) M to 10(-13) M dose range. Both agents significantly enhanced 'early', but not 'total' E rosette formation. Peak enhancement above control values occurred at 10(-7) M (72%) and 10(-9) M (69%) for carbachol and 10(-5) M (70%) and 10(-7) M (70%) for DBCGMP. Kinetic studies showed a rapid onset of enhancement (2.5 min) for carbachol, whereas DBCGMP required 15 min for significant enhancement to occur. The muscurinic nature of carbachol enhancement of E rosettes was demonstrated. Atropine at 10(-7) M completely abolished the carbachol effect while showing little inhibition of the DBCGMP effect on rosette formation. These studies indicate that the cholinergic stimuli carbachl and DBCGMP significantly enhance the 'early' E rosette former in man. Human T lymphocytes appear to have functional cholinergic receptors that can be blocked by the muscurinic antagonist atropine. The role of the cyclic nucleotides and their stimulants on the immune system is incompletely understood, but it would appear that they are extremely important in the differentiation and function of the T lymphocyte. E rosette formation may be a useful model in man for studying the effects of the cyclic nucleotides on the human T lymphocyte."} {"id": "PMID:180182", "title": "Characterization of effector lymphocytes associated with immunity to murine sarcoma virus (MSV) induced tumors. I. Physical properties of cytolytic T lymphocytes generated in vitro and of their immediate progenitors.", "content": "Cytolytic T lymphocytes (CTL) were generated in secondary mixed leukocyte-tumor cell cultures (MLTC) with syngeneic RB1-5 tumor cells as stimulating cells and with responding spleen cells from regressor mice that had rejected a murine sarcoma virus (MSV)-induced tumor. CTL precursor cells were found to be exclusively of thymic origin and non-T cells were apparently not required for CTL generation. When the size variations of CTL from syngeneic MLTC were analyzed by velocity sedimentation it appeared that a transition from small precursor cells to larger effector cells occurred during the first 5 days in culture; this change in cell size was then followed by a shift toward small-sized cells. Furthermore, the CTL generated in syngeneic MLTC in the MSV tumor immune system were compared with those CTL obtained in allogeneic mixed leukocyte cultures (MLC) and were shown to exhibit fundamental similarities.", "contents": "Characterization of effector lymphocytes associated with immunity to murine sarcoma virus (MSV) induced tumors. I. Physical properties of cytolytic T lymphocytes generated in vitro and of their immediate progenitors. Cytolytic T lymphocytes (CTL) were generated in secondary mixed leukocyte-tumor cell cultures (MLTC) with syngeneic RB1-5 tumor cells as stimulating cells and with responding spleen cells from regressor mice that had rejected a murine sarcoma virus (MSV)-induced tumor. CTL precursor cells were found to be exclusively of thymic origin and non-T cells were apparently not required for CTL generation. When the size variations of CTL from syngeneic MLTC were analyzed by velocity sedimentation it appeared that a transition from small precursor cells to larger effector cells occurred during the first 5 days in culture; this change in cell size was then followed by a shift toward small-sized cells. Furthermore, the CTL generated in syngeneic MLTC in the MSV tumor immune system were compared with those CTL obtained in allogeneic mixed leukocyte cultures (MLC) and were shown to exhibit fundamental similarities."} {"id": "PMID:180183", "title": "Chromatographic separation of gram quantities of immunoglobulins from porcine colostrium against transmissible gastroenteritis virus.", "content": "Similar immunoglobulin (Ig) classes were obtained from porcine colodtral whey by either column or batch chromatographic procedures; a stepwise buffer elution technique was used. Specific transmissible gastroenteritis virus neutralizing antibody was found in the 4 major fractions eluted comprising of IgG1, IgG2, IgA, and IgM. The IgG1, and IgG2 were essentially homogeneous, and the IgA- AND IgM-rich fractions had to be recycled several times through Sephadex G-200 to obtain pure IgA and IgM that had specific virus neutralizing activities per mg of protein of 342.1 and 302. 4, compared with 7.6 for IgG. By a combination of the batch chromatographic procedures and gel filtration, gram amounts of specific Ig could be fractionated from the same colostrum.", "contents": "Chromatographic separation of gram quantities of immunoglobulins from porcine colostrium against transmissible gastroenteritis virus. Similar immunoglobulin (Ig) classes were obtained from porcine colodtral whey by either column or batch chromatographic procedures; a stepwise buffer elution technique was used. Specific transmissible gastroenteritis virus neutralizing antibody was found in the 4 major fractions eluted comprising of IgG1, IgG2, IgA, and IgM. The IgG1, and IgG2 were essentially homogeneous, and the IgA- AND IgM-rich fractions had to be recycled several times through Sephadex G-200 to obtain pure IgA and IgM that had specific virus neutralizing activities per mg of protein of 342.1 and 302. 4, compared with 7.6 for IgG. By a combination of the batch chromatographic procedures and gel filtration, gram amounts of specific Ig could be fractionated from the same colostrum."} {"id": "PMID:180184", "title": "High density lipoprotein (HDL) polymorphisms in rabbit. I. A comparative study of rabbit and human serum high density lipoprotein.", "content": "Different classes of rabbit serum lipoprotein were prepared by ultracentrifugal flotation at densities 1-006, 1-063 and 1-21 g/ml. Agarose gel electrophoresis on rabbit whole serum and the serum fractions with different densities showed that this technique separates the different lipoprotein classes reasonably well. The electrophoretic mobility of the different lipoprotein classes of rabbit serum seems to be similar to that of the human lipoproteins, with the exception of alpha1-lipoprotein which had a greater mobility than human alpha1-lipoprotein. The chemical composition of rabbit high density lipoprotein (HDL)p was fairly similar to that of human HDL although the former seems to be richer in triglycerides. HDL was, after isolation by ultracentrifugal flotation at density 1-21, delipidated and submitted to gel filtration on Sephadex G-200 in 8 M urea. The major protein fraction of rabbit apo HDL corresponds in elution volume to that of the major fraction of human apo HDL, apoA-I. A protein fraction corresponding to human apoA-II does not seem to be present in rabbit HDL in demonstrable amounts. The rabbit protein fraction sometimes appearing in the area corresponding to human apoA-II could not be found to be affected by the reduction and alkylation method after which human poA-II splits into two identical chains.", "contents": "High density lipoprotein (HDL) polymorphisms in rabbit. I. A comparative study of rabbit and human serum high density lipoprotein. Different classes of rabbit serum lipoprotein were prepared by ultracentrifugal flotation at densities 1-006, 1-063 and 1-21 g/ml. Agarose gel electrophoresis on rabbit whole serum and the serum fractions with different densities showed that this technique separates the different lipoprotein classes reasonably well. The electrophoretic mobility of the different lipoprotein classes of rabbit serum seems to be similar to that of the human lipoproteins, with the exception of alpha1-lipoprotein which had a greater mobility than human alpha1-lipoprotein. The chemical composition of rabbit high density lipoprotein (HDL)p was fairly similar to that of human HDL although the former seems to be richer in triglycerides. HDL was, after isolation by ultracentrifugal flotation at density 1-21, delipidated and submitted to gel filtration on Sephadex G-200 in 8 M urea. The major protein fraction of rabbit apo HDL corresponds in elution volume to that of the major fraction of human apo HDL, apoA-I. A protein fraction corresponding to human apoA-II does not seem to be present in rabbit HDL in demonstrable amounts. The rabbit protein fraction sometimes appearing in the area corresponding to human apoA-II could not be found to be affected by the reduction and alkylation method after which human poA-II splits into two identical chains."} {"id": "PMID:180186", "title": "Regulation of cell cycles.", "content": "Of the major achievements in cell biology during the last 25 years, none is more important than the understanding of regulation of cell cycles. In 1953 two fundamental observations concerning DNA were made. Watson and Crick suggested that the three-dimensional structure of DNA exists as a double helix with specific base pairings, and Howard and Pelc observed that DNA is replicated during a specific phase in the mitotic cycle. Thus developed the theory of cell cycles. Next, investigators explored which events occur during each phase of the cycle and what controls the readout of the genes of proliferation or differentiation. In 1961, Jacob and Monod proposed that for prokaryotic cells the operon is the mechanism which controls the readout of the genes; and by the end of the 1960s, several investigators had defined the role of cyclic AMP and its mechanism of action at the gene level. The control mechanisms of eukaryotic cells are less well defined. Basically there are two types of regulatory molecules: those that arrive at the cell surface and send messages inside the cell; and those that enter the cell, bind to receptors, and then enter the nucleus to interact with the genes. During the past five to ten years, the cell surface and its receptors have received considerable attention as the recognition and control areas for cell proliferation and differentiation, and currently the role of the cyclic nucleotides and prostaglandins is being investigated. Various model systems are now available for detailed studies of these control mechanisms.", "contents": "Regulation of cell cycles. Of the major achievements in cell biology during the last 25 years, none is more important than the understanding of regulation of cell cycles. In 1953 two fundamental observations concerning DNA were made. Watson and Crick suggested that the three-dimensional structure of DNA exists as a double helix with specific base pairings, and Howard and Pelc observed that DNA is replicated during a specific phase in the mitotic cycle. Thus developed the theory of cell cycles. Next, investigators explored which events occur during each phase of the cycle and what controls the readout of the genes of proliferation or differentiation. In 1961, Jacob and Monod proposed that for prokaryotic cells the operon is the mechanism which controls the readout of the genes; and by the end of the 1960s, several investigators had defined the role of cyclic AMP and its mechanism of action at the gene level. The control mechanisms of eukaryotic cells are less well defined. Basically there are two types of regulatory molecules: those that arrive at the cell surface and send messages inside the cell; and those that enter the cell, bind to receptors, and then enter the nucleus to interact with the genes. During the past five to ten years, the cell surface and its receptors have received considerable attention as the recognition and control areas for cell proliferation and differentiation, and currently the role of the cyclic nucleotides and prostaglandins is being investigated. Various model systems are now available for detailed studies of these control mechanisms."} {"id": "PMID:180187", "title": "Viral diseases of the skin, 1975: a 25-year perspective.", "content": "Most of the major advances in modern virology during the past 25 years have been due principally to the development of refined laboratory techniques and tools and have provided a fund of new knowledge and information about the nature of viral infection and pathogenesis. One group of viruses of interest to dermatologists, the herpesviruses, is undergoing intensive biochemical investigation to determine whether it is carcinogenic. As a result of the success of the World Health Organization's campaign to eradicate smallpox, it is predicted that by the end of 1976, smallpox will have been eradicated. Other viruses of dermatologic interest which are now being studied include the agents of warts, molluscum contagiosum, cat-scratch disease, and enteroviruses. Current research in the field of viral chemotherapy may provide the basis for successfully treating these diseases in the future.", "contents": "Viral diseases of the skin, 1975: a 25-year perspective. Most of the major advances in modern virology during the past 25 years have been due principally to the development of refined laboratory techniques and tools and have provided a fund of new knowledge and information about the nature of viral infection and pathogenesis. One group of viruses of interest to dermatologists, the herpesviruses, is undergoing intensive biochemical investigation to determine whether it is carcinogenic. As a result of the success of the World Health Organization's campaign to eradicate smallpox, it is predicted that by the end of 1976, smallpox will have been eradicated. Other viruses of dermatologic interest which are now being studied include the agents of warts, molluscum contagiosum, cat-scratch disease, and enteroviruses. Current research in the field of viral chemotherapy may provide the basis for successfully treating these diseases in the future."} {"id": "PMID:180188", "title": "The culture of skin. A review of theories and experimental methods.", "content": "Two main criticisms can be leveled against the standard methods of skin culture: they are poorly quantifiable and the cultured cell populations are heterogeneous. A new technique based mainly on enzymatic dissociation allows specific cell types to be extracted from the skin before cultivation. In this way, separate cultures of epidermal keratinocytes and dermal fibroblasts can be obtained from the same piece of skin. These purified systems have been used to study the kinetics of epidermal cell growth and to quantify the effect of various chemically defined substances on the growth and differentiation of keratinocytes. With further refinements in technique, purified populations of melanocytes can be extracted. The co-culture of pigmented melanocytes with albino keratinocytes has been proposed as a model to study pigment donation in vitro. The usual organ culture technique, including the use of large explants of skin immersed in the culture fluid, has been modified to show that adult human skin partially regenerates in vitro and that mitotic activity goes on for months in the regenerated epidermis. The use of nucleic acid hybridization techniques, combined with skin cell cultures from human tumors, opens new avenues of research on human cancer.", "contents": "The culture of skin. A review of theories and experimental methods. Two main criticisms can be leveled against the standard methods of skin culture: they are poorly quantifiable and the cultured cell populations are heterogeneous. A new technique based mainly on enzymatic dissociation allows specific cell types to be extracted from the skin before cultivation. In this way, separate cultures of epidermal keratinocytes and dermal fibroblasts can be obtained from the same piece of skin. These purified systems have been used to study the kinetics of epidermal cell growth and to quantify the effect of various chemically defined substances on the growth and differentiation of keratinocytes. With further refinements in technique, purified populations of melanocytes can be extracted. The co-culture of pigmented melanocytes with albino keratinocytes has been proposed as a model to study pigment donation in vitro. The usual organ culture technique, including the use of large explants of skin immersed in the culture fluid, has been modified to show that adult human skin partially regenerates in vitro and that mitotic activity goes on for months in the regenerated epidermis. The use of nucleic acid hybridization techniques, combined with skin cell cultures from human tumors, opens new avenues of research on human cancer."} {"id": "PMID:180189", "title": "Evaluation of 6-azauridine and 5-iododeoxyuridine in the treatment of experimental viral infections.", "content": "The potential antiviral activity of 6-azauridine and 5-iododeoxyuridine was evaluated in a coordinated study at five institutions. Experimental models in five species, the mouse, rabbit, swine, cat, and ferret, were established with use of 10 viruses: Herpesvirus hominis types 1 and 2, murine cytomegalovirus, vaccinia virus, Shope fibroma virus, transmissible gastroenteritis virus, swine influenza virus, feline viral rhinotracheitis virus, feline panleukopenia virus, and ferret distemper virus. Criteria for selection were: (1) representation from a number of major groups of viruses, (2) reproduction of natural routes of infection, and (3) simulation of potentially treatable viral infections of man. Antiviral activity was observed for 5-iododeoxyuridine in H. hominis infections in hairless mice and influenza in swine, and a slight degree of efficacy was noted in rabbits infected with Shope fibroma virus. Toxicity was also observed in most of the experimental models. There was a suggestion of antiviral activity with 6-azauridine in swine infected with transmissible gastroenteritis virus; however, enhancement of disease and some toxicity were seen in most of the other models. Efficacy of these two compounds was not well substantiated by these studies.", "contents": "Evaluation of 6-azauridine and 5-iododeoxyuridine in the treatment of experimental viral infections. The potential antiviral activity of 6-azauridine and 5-iododeoxyuridine was evaluated in a coordinated study at five institutions. Experimental models in five species, the mouse, rabbit, swine, cat, and ferret, were established with use of 10 viruses: Herpesvirus hominis types 1 and 2, murine cytomegalovirus, vaccinia virus, Shope fibroma virus, transmissible gastroenteritis virus, swine influenza virus, feline viral rhinotracheitis virus, feline panleukopenia virus, and ferret distemper virus. Criteria for selection were: (1) representation from a number of major groups of viruses, (2) reproduction of natural routes of infection, and (3) simulation of potentially treatable viral infections of man. Antiviral activity was observed for 5-iododeoxyuridine in H. hominis infections in hairless mice and influenza in swine, and a slight degree of efficacy was noted in rabbits infected with Shope fibroma virus. Toxicity was also observed in most of the experimental models. There was a suggestion of antiviral activity with 6-azauridine in swine infected with transmissible gastroenteritis virus; however, enhancement of disease and some toxicity were seen in most of the other models. Efficacy of these two compounds was not well substantiated by these studies."} {"id": "PMID:180190", "title": "In vitro stimulation of lymphocytes of donors seronegative for Epstein-Barr virus by preparations of inactivated Epstein-Barr virus.", "content": "Heat-inactivated preparations of Epstein-Barr virus stimulated human lymphocytes as assayed by incorporation of [(3)H]thymidine. The inactivated Epstein-Barr virus stimulated the lymphocytes of all five seropositive donors, 11 of 14 seronegative donors (aged eight to 26 years), and none of 15 neonates. Control antigens prepared from a human lymphoid cell line devoid of the Epstein-Barr virus genome did not stimulate the lymphocytes of seronegative donors. Fetal calf serum at the concentration used for suspension of Epstein-Barr virus did not stimulate or only minimally stimulated the lymphocytes of seronegative donors. The reactivity of the histocompatibility antigens found on human lymphocytes was abolished by procedures used for inactivation of the virus.", "contents": "In vitro stimulation of lymphocytes of donors seronegative for Epstein-Barr virus by preparations of inactivated Epstein-Barr virus. Heat-inactivated preparations of Epstein-Barr virus stimulated human lymphocytes as assayed by incorporation of [(3)H]thymidine. The inactivated Epstein-Barr virus stimulated the lymphocytes of all five seropositive donors, 11 of 14 seronegative donors (aged eight to 26 years), and none of 15 neonates. Control antigens prepared from a human lymphoid cell line devoid of the Epstein-Barr virus genome did not stimulate the lymphocytes of seronegative donors. Fetal calf serum at the concentration used for suspension of Epstein-Barr virus did not stimulate or only minimally stimulated the lymphocytes of seronegative donors. The reactivity of the histocompatibility antigens found on human lymphocytes was abolished by procedures used for inactivation of the virus."} {"id": "PMID:180191", "title": "Treatment of infections due to Herpesvirus in humans: a critical review of the state of the art.", "content": "Results of experimental trials with antiviral agents in humans have varied from encouraging to controversial to negative, usually as a result of the difficulty in defining the true therapeutic index (ratio of efficacy to toxicity) of toxic drugs for the treatment of diseases that are potentially severely debilitating or lethal. Reasons for current difficulties relate mainly to inadequacies of preclinical studies and the lack of appropriate controls. The inadequacies include poor definition of the effect of drugs or viruses on cellular metabolism, incomplete pharmacologic studies in animals or humans, and, because of the latter, inappropriate animal models. In human trials, historical data have often been used instead of true controls because of the presumed severity of candidate diseases. Use of such data led to a false impression of drug efficacy, an impression later refuted when proper control studies demonstrated that the range of disease was much greater than had been previously supposed. Data bearing on these points for the most commonly employed experimental compounds (cytosine arabinoside, adenine arabinoside, and 5-iodo-2'-deoxyuridine) are contrasted to highlight difficulties as well as to provide perspectives for antiviral chemotherapy of herpesvirus infections.", "contents": "Treatment of infections due to Herpesvirus in humans: a critical review of the state of the art. Results of experimental trials with antiviral agents in humans have varied from encouraging to controversial to negative, usually as a result of the difficulty in defining the true therapeutic index (ratio of efficacy to toxicity) of toxic drugs for the treatment of diseases that are potentially severely debilitating or lethal. Reasons for current difficulties relate mainly to inadequacies of preclinical studies and the lack of appropriate controls. The inadequacies include poor definition of the effect of drugs or viruses on cellular metabolism, incomplete pharmacologic studies in animals or humans, and, because of the latter, inappropriate animal models. In human trials, historical data have often been used instead of true controls because of the presumed severity of candidate diseases. Use of such data led to a false impression of drug efficacy, an impression later refuted when proper control studies demonstrated that the range of disease was much greater than had been previously supposed. Data bearing on these points for the most commonly employed experimental compounds (cytosine arabinoside, adenine arabinoside, and 5-iodo-2'-deoxyuridine) are contrasted to highlight difficulties as well as to provide perspectives for antiviral chemotherapy of herpesvirus infections."} {"id": "PMID:180192", "title": "Effect of a topical interferon inducer on rhinovirus infections in volunteers.", "content": "Six controlled trials of a topical interferon inducer, N',N'-diotadecyl-N',N'-bis-(2-hydroxyethyl) propanediamine (CP 20961), against rhinovirus infection in volunteers were reviewed. Controls were the drug vehicle (which consisted of a mixture of polysorbate-80 in gylcerol and saline), saline only, and oral lactose. Multiple doses of the inducer given before challenge in any of three regimens reduced the symptomatic response to viral infection. Treatment with three doses of drug the day before challenge enhanced the interferon response to virus; four days of treatment with either the drug or its vehicle before challenge produced a refractoriness to further interferon induction. Both the drug and its vehicle were capable of inducing nasal interferon. When interferon was present at the time of viral inoculation, symptoms were reduced with or without an increase in the interferon response to infection. The rates of infection and illness were increased after a single dose of drug and decreased after a single dose of the vehicle alone.", "contents": "Effect of a topical interferon inducer on rhinovirus infections in volunteers. Six controlled trials of a topical interferon inducer, N',N'-diotadecyl-N',N'-bis-(2-hydroxyethyl) propanediamine (CP 20961), against rhinovirus infection in volunteers were reviewed. Controls were the drug vehicle (which consisted of a mixture of polysorbate-80 in gylcerol and saline), saline only, and oral lactose. Multiple doses of the inducer given before challenge in any of three regimens reduced the symptomatic response to viral infection. Treatment with three doses of drug the day before challenge enhanced the interferon response to virus; four days of treatment with either the drug or its vehicle before challenge produced a refractoriness to further interferon induction. Both the drug and its vehicle were capable of inducing nasal interferon. When interferon was present at the time of viral inoculation, symptoms were reduced with or without an increase in the interferon response to infection. The rates of infection and illness were increased after a single dose of drug and decreased after a single dose of the vehicle alone."} {"id": "PMID:180193", "title": "Four compounds active against rhinovirus: comparison in vitro and in volunteers.", "content": "Four unrelated compounds active against rhinovirus were compared in tissue culture, and three of them were used in volunteers challenged with rhinovirus. The compounds were the triazino-indole SKF 40491, the substituted oxadiazole GLR9-338, the imidazo-thiazole RP L9326, and the guanidine derivative ICI 73,602. The abilities of these compounds to reduce the yield of rhinovirus types 3, 4, 9, and 31 from HeLa cells or fibroblasts were compared, and a sensitive serotype was chosen for each challenge experiment in humans. In doubleblind studies volunteers received intranasal medication before and after the challenge. Daily scoring of symptoms and titration of virus in nasal washings showed that subjects treated with SKF, GL, and RP all shed less virus than their corresponding placebo groups, significantly so in the cases of GL and RP. Clinical reactions were also less severe in volunteers treated with RP.", "contents": "Four compounds active against rhinovirus: comparison in vitro and in volunteers. Four unrelated compounds active against rhinovirus were compared in tissue culture, and three of them were used in volunteers challenged with rhinovirus. The compounds were the triazino-indole SKF 40491, the substituted oxadiazole GLR9-338, the imidazo-thiazole RP L9326, and the guanidine derivative ICI 73,602. The abilities of these compounds to reduce the yield of rhinovirus types 3, 4, 9, and 31 from HeLa cells or fibroblasts were compared, and a sensitive serotype was chosen for each challenge experiment in humans. In doubleblind studies volunteers received intranasal medication before and after the challenge. Daily scoring of symptoms and titration of virus in nasal washings showed that subjects treated with SKF, GL, and RP all shed less virus than their corresponding placebo groups, significantly so in the cases of GL and RP. Clinical reactions were also less severe in volunteers treated with RP."} {"id": "PMID:180194", "title": "Sensitivity of rhinoviruses to human leukocyte and fibroblast interferons.", "content": "Rhinoviruses were tested for sensitivity to human interferon from two sources: human leukosytes induced with Sendai virus and human diploid fibroblasts induced with polyriboinosinic-polyribocytidylic acid. Twenty-five serotypes of rhinovirus were tested against fibroblast interferon in HeLa cells, and five serotypes were evaluated in fibroblast cultures against fibroblast and leukocyte interferons. Sensitivity varied widely in the HeLa cell assay; rhinovirus type 10 was inhibited by approximately 20-40 units of interferon, whereas rhinovirus type 15 was not inhibited by 5,120 units; the significance of this observation is unclear. In contrast, when fibroblast cultures were used in the assay system, five selected serotypes, including rhinovirus types 10 and 15, had similar levels of sensitivity (0.5-5.0 units) to fibroblast or leukocyte interferon.", "contents": "Sensitivity of rhinoviruses to human leukocyte and fibroblast interferons. Rhinoviruses were tested for sensitivity to human interferon from two sources: human leukosytes induced with Sendai virus and human diploid fibroblasts induced with polyriboinosinic-polyribocytidylic acid. Twenty-five serotypes of rhinovirus were tested against fibroblast interferon in HeLa cells, and five serotypes were evaluated in fibroblast cultures against fibroblast and leukocyte interferons. Sensitivity varied widely in the HeLa cell assay; rhinovirus type 10 was inhibited by approximately 20-40 units of interferon, whereas rhinovirus type 15 was not inhibited by 5,120 units; the significance of this observation is unclear. In contrast, when fibroblast cultures were used in the assay system, five selected serotypes, including rhinovirus types 10 and 15, had similar levels of sensitivity (0.5-5.0 units) to fibroblast or leukocyte interferon."} {"id": "PMID:180195", "title": "Photodynamic inactivation in recurrent infections with herpes simplex virus.", "content": "Photodynamic inactivation with neutral red (a heterotricyclic dye) and light was evaluated in a placebo-controlled study of 170 episodes of recurrent infection with herpes simplex virus in 96 patients. The technique inactivated herpes simplex virus in vitro. However, no beneficial effect, either on the rate of resolution of herpetic lesions or on the interval to subsequent recurrences, was observed in treated patients. These negative results should not deter further investigation of photodynamic inactivation as a potential treatment for herpes simplex virus infections, but the clinical application of this form of therapy should be limited to properly controlled studies until its efficacy is proven.", "contents": "Photodynamic inactivation in recurrent infections with herpes simplex virus. Photodynamic inactivation with neutral red (a heterotricyclic dye) and light was evaluated in a placebo-controlled study of 170 episodes of recurrent infection with herpes simplex virus in 96 patients. The technique inactivated herpes simplex virus in vitro. However, no beneficial effect, either on the rate of resolution of herpetic lesions or on the interval to subsequent recurrences, was observed in treated patients. These negative results should not deter further investigation of photodynamic inactivation as a potential treatment for herpes simplex virus infections, but the clinical application of this form of therapy should be limited to properly controlled studies until its efficacy is proven."} {"id": "PMID:180196", "title": "Genital herpetic infection in men and women: clinical course and effect of topical application of adenine arabinoside.", "content": "Sixty-three episodes of genital herpetic infection in 55 men and 45 episodes in 42 women were randomly assigned to topical treatment with 3% adenine arabinoside, topical treatment with placebo ointment, or no therapy. In addition, 10 episodes in women who were not randomly assigned to therapy were evaluated and followed. Clinical evaluation and viral cultures were done on day 3, day 8, and weekly thereafter until the lesions had healed. The natural clinical course of genital herpetic infection was defined in patients given placebo or no therapy. Patients with a history of previous genital herpetic infection had significantly less pain, few lesions, and shorter duration of illness and viral shedding than patients who had no history of previous genital infection with Herpesvirus. An unexpected finding was that 87% of women experiencing their first episode of genital herpetic infection had cervical cultures positive for Herpesvirus hominis, whereas only 4% of women with recurrent herpetic infection had a positive cervical culture. Treatment with 3% adenine arabinoside did not influence the course of either primary or recurrent genital infection with Herpesvirus.", "contents": "Genital herpetic infection in men and women: clinical course and effect of topical application of adenine arabinoside. Sixty-three episodes of genital herpetic infection in 55 men and 45 episodes in 42 women were randomly assigned to topical treatment with 3% adenine arabinoside, topical treatment with placebo ointment, or no therapy. In addition, 10 episodes in women who were not randomly assigned to therapy were evaluated and followed. Clinical evaluation and viral cultures were done on day 3, day 8, and weekly thereafter until the lesions had healed. The natural clinical course of genital herpetic infection was defined in patients given placebo or no therapy. Patients with a history of previous genital herpetic infection had significantly less pain, few lesions, and shorter duration of illness and viral shedding than patients who had no history of previous genital infection with Herpesvirus. An unexpected finding was that 87% of women experiencing their first episode of genital herpetic infection had cervical cultures positive for Herpesvirus hominis, whereas only 4% of women with recurrent herpetic infection had a positive cervical culture. Treatment with 3% adenine arabinoside did not influence the course of either primary or recurrent genital infection with Herpesvirus."} {"id": "PMID:180197", "title": "Interferon in treatment of dendritic keratitis in humans: a preliminary report.", "content": "Seventy-three patients with herpetic epithelial keratitis were randomly divided into three groups and were treated by local applications of human leukocyte interferon, thermocautery plus human leukocyte interferon, or thermocautery plus mock human leukocyte interferon to obtain information on whether therapy with human leukocyte interferon can serve as a substitute for mechanical debridement of the involved epithelium or can improve the results when given as additional therapy. Fifty-five patients (75%) yielded herpes simplex virus before treatment, and only the results in these patients with keratitis of proved viral etiology were included in the analysis. These results indicated that mechanical debridement cannot be replaced with local application of human leukocyte interferon (3-4 X 10(4) units per day). When given in addition to thermocautery, human leukocyte interferon may have been of some value in a number of patients. However, the results were not statistically significant. A more potent dosage of human leukocyte interferon might provide better results.", "contents": "Interferon in treatment of dendritic keratitis in humans: a preliminary report. Seventy-three patients with herpetic epithelial keratitis were randomly divided into three groups and were treated by local applications of human leukocyte interferon, thermocautery plus human leukocyte interferon, or thermocautery plus mock human leukocyte interferon to obtain information on whether therapy with human leukocyte interferon can serve as a substitute for mechanical debridement of the involved epithelium or can improve the results when given as additional therapy. Fifty-five patients (75%) yielded herpes simplex virus before treatment, and only the results in these patients with keratitis of proved viral etiology were included in the analysis. These results indicated that mechanical debridement cannot be replaced with local application of human leukocyte interferon (3-4 X 10(4) units per day). When given in addition to thermocautery, human leukocyte interferon may have been of some value in a number of patients. However, the results were not statistically significant. A more potent dosage of human leukocyte interferon might provide better results."} {"id": "PMID:180198", "title": "Adenine arabinoside for therapy of herpes zoster in immunosuppressed patients: preliminary results of a collaborative study.", "content": "Eighty-seven immunosuppressed patients (53 with localized and 34 with disseminated herpes zoster) from 10 institutions were enrolled in a controlled therapeutic trial of adenine arabinoside. A crossover design was employed; thus, 47 patients received drug for five days and then received placebo, and 40 were given the two substances in the opposite order. Resolution of acute pain and the cutaneous lesions were graded during a 10-day observation period. During the initial five-day period, treated patients showed a statistically significant resolution of pain and cutaneous lesions. Surprisingly, in many untreated patients, natural resolution occurred during this period so that crossover data could not be adequately assessed. Effects on visceral disease also could not be judged, because such disease was uncommon. Ratings of late complications such as postherpetic neuralgia were confused by the crossover design. Toxicity posed no problem. The data further emphasized the potential usefulness of adenine arabinoside as an antiviral chemotherapeutic agent, but also clearly indicated the need for a double-blind study to define this usefulness and to determine how it can most practically be used, if the risk-benefit factor remains favorable.", "contents": "Adenine arabinoside for therapy of herpes zoster in immunosuppressed patients: preliminary results of a collaborative study. Eighty-seven immunosuppressed patients (53 with localized and 34 with disseminated herpes zoster) from 10 institutions were enrolled in a controlled therapeutic trial of adenine arabinoside. A crossover design was employed; thus, 47 patients received drug for five days and then received placebo, and 40 were given the two substances in the opposite order. Resolution of acute pain and the cutaneous lesions were graded during a 10-day observation period. During the initial five-day period, treated patients showed a statistically significant resolution of pain and cutaneous lesions. Surprisingly, in many untreated patients, natural resolution occurred during this period so that crossover data could not be adequately assessed. Effects on visceral disease also could not be judged, because such disease was uncommon. Ratings of late complications such as postherpetic neuralgia were confused by the crossover design. Toxicity posed no problem. The data further emphasized the potential usefulness of adenine arabinoside as an antiviral chemotherapeutic agent, but also clearly indicated the need for a double-blind study to define this usefulness and to determine how it can most practically be used, if the risk-benefit factor remains favorable."} {"id": "PMID:180199", "title": "Toxicity of adenine arabinoside in humans.", "content": "Six forms of reversible adverse reactions to adenine arabinoside (vidarabine) were observed in a two-year period among 42 patients (19 of whom had lymphomas, leukemias, or other malignancies) who were treated for complicated infections with varicella-zoster or herpes simplex virus. Six patients received placebo. Ten patients received 10 mg of adenine arabinoside/kg per day; three received 15 mg/kg; 22 received 20 mg/kg; and one received 30 mg/kg. Patients were treated (by continuous intravenous injection) for an average of seven days. Toxic effects were nausea and vomiting, weight loss, weakness (often with impaired ambulation), megaloblastosis in erythroid series in bone marrow, tremors five to seven days after the start of therapy (including tremors in one patient with abnormal electroencephalograms that were consistent with toxic-metabolic encephalopathy), and thrombophlebitis at the intravenous site. Side effects clearly predominated in patients who received 20 mg/kg per day. Therefore, treatment with 10 mg/kg per day appears preferable until the relation of toxicity to dosage level can be clarified.", "contents": "Toxicity of adenine arabinoside in humans. Six forms of reversible adverse reactions to adenine arabinoside (vidarabine) were observed in a two-year period among 42 patients (19 of whom had lymphomas, leukemias, or other malignancies) who were treated for complicated infections with varicella-zoster or herpes simplex virus. Six patients received placebo. Ten patients received 10 mg of adenine arabinoside/kg per day; three received 15 mg/kg; 22 received 20 mg/kg; and one received 30 mg/kg. Patients were treated (by continuous intravenous injection) for an average of seven days. Toxic effects were nausea and vomiting, weight loss, weakness (often with impaired ambulation), megaloblastosis in erythroid series in bone marrow, tremors five to seven days after the start of therapy (including tremors in one patient with abnormal electroencephalograms that were consistent with toxic-metabolic encephalopathy), and thrombophlebitis at the intravenous site. Side effects clearly predominated in patients who received 20 mg/kg per day. Therefore, treatment with 10 mg/kg per day appears preferable until the relation of toxicity to dosage level can be clarified."} {"id": "PMID:180200", "title": "Effect of human exogenous leukocyte interferon in cytomegalovirus infections.", "content": "Human leukocyte interferon was injected into nine patients with cytomegalovirus infections; four of these patients were congenitally infected, and five had acquired infections. In three patients viruria was completely inhibited. In five patients viral excretion in the urine was only transiently inhibited. Viremia was not significantly suppressed. The lymphocyte response to phytohemagglutinin was suppressed in two patients.", "contents": "Effect of human exogenous leukocyte interferon in cytomegalovirus infections. Human leukocyte interferon was injected into nine patients with cytomegalovirus infections; four of these patients were congenitally infected, and five had acquired infections. In three patients viruria was completely inhibited. In five patients viral excretion in the urine was only transiently inhibited. Viremia was not significantly suppressed. The lymphocyte response to phytohemagglutinin was suppressed in two patients."} {"id": "PMID:180201", "title": "Effect of leukocyte interferon on urinary excretion of cytomegalovirus by infants.", "content": "Five infants with symptomatic cytomegalovirus infections and high urinary titers of cytomegalovirus were treated with interferon in doses of 1.7-3.5 X 10(5) reference units/kg per day for seven to 14 days. Six courses of treatment were given. One of two infants treated with the largest dose of interferon had transient suppression of viruria; no suppression was noted during the other five courses of treatment. Adverse effects noted included a low rate of weight gain, a transient elevation of serum aspartate aminotransferase and fever. Further trials are needed to determine whether larger doses of a more purified preparation of interferon will eliminate viruria in infants with sytomegalovirus infection, but careful assessment of toxicity will be necessary in this population of patients.", "contents": "Effect of leukocyte interferon on urinary excretion of cytomegalovirus by infants. Five infants with symptomatic cytomegalovirus infections and high urinary titers of cytomegalovirus were treated with interferon in doses of 1.7-3.5 X 10(5) reference units/kg per day for seven to 14 days. Six courses of treatment were given. One of two infants treated with the largest dose of interferon had transient suppression of viruria; no suppression was noted during the other five courses of treatment. Adverse effects noted included a low rate of weight gain, a transient elevation of serum aspartate aminotransferase and fever. Further trials are needed to determine whether larger doses of a more purified preparation of interferon will eliminate viruria in infants with sytomegalovirus infection, but careful assessment of toxicity will be necessary in this population of patients."} {"id": "PMID:180202", "title": "Effective antiviral prophylaxis and therapy by systemic application of human interferon in immunosuppressed monkeys.", "content": "Rhesus monkeys treated with antilymphocytic globulin were infected with vaccinia virus or with Medical Lake macaque Herpesvirus. At the sites of inoculation of vaccinia virus, animals not treated with interferon developed typical pustulous reactions and then smaller secondary lesions. Human leukocyte interferon (5 X 10(5) international units per day) injected intramuscularly, either from one day before to three days after infection or for seven days beginning on the first day of primary reaction, suppressed the development of secondary lesions but did not influence the primary reaction. Infection with Herpesvirus caused a vesicular rash similar to that of human varicella. Through prophylactic treatment with human leukocyte interferon, the disease was completely averted in two of four monkeys, and in the other two the rash was delayed. Therapy initiated when the first lesions appeared prevented the enlargement and generalization of lesions in all of four monkeys. Formation of serum antibodies was only slightly influenced by human leukocyte interferon. The results suggest that systemic treatment with interferon, begun either prophylactically or therapeutically with the first symptoms, can be effective in immunosuppressed patients.", "contents": "Effective antiviral prophylaxis and therapy by systemic application of human interferon in immunosuppressed monkeys. Rhesus monkeys treated with antilymphocytic globulin were infected with vaccinia virus or with Medical Lake macaque Herpesvirus. At the sites of inoculation of vaccinia virus, animals not treated with interferon developed typical pustulous reactions and then smaller secondary lesions. Human leukocyte interferon (5 X 10(5) international units per day) injected intramuscularly, either from one day before to three days after infection or for seven days beginning on the first day of primary reaction, suppressed the development of secondary lesions but did not influence the primary reaction. Infection with Herpesvirus caused a vesicular rash similar to that of human varicella. Through prophylactic treatment with human leukocyte interferon, the disease was completely averted in two of four monkeys, and in the other two the rash was delayed. Therapy initiated when the first lesions appeared prevented the enlargement and generalization of lesions in all of four monkeys. Formation of serum antibodies was only slightly influenced by human leukocyte interferon. The results suggest that systemic treatment with interferon, begun either prophylactically or therapeutically with the first symptoms, can be effective in immunosuppressed patients."} {"id": "PMID:180203", "title": "Immunopotentiation and antiviral chemotherapy in a suckling rat model of herpesvirus encephalitis.", "content": "Encephalitis was induced in 10-day-old Wistar rats by intraperitoneal injection of approximately 100 50% tissue culture infective doses of herpes simplex virus type 2. Treatment regimens included immunopotentiation with levamisole and combined therapy with levamisole and an antiviral agent, adenine arabinoside. Rats treated with levamisole alone had significantly higher rates of survival than placebo-treated controls 14 days after injection of virus. Combination therapy with levamisole and adenine arabinoside prolonged survival, but there was no significant difference between treated animals and controls given placebo. Because adenine arabinoside inhibits the beneficial effect of levamisole in this model, antiviral chemotherapy in conjunction with immunopotentiation should be used with caution in humans. Further studies will be necessary to determine the value of immunopotentiation therapy in the treatment of life-threatening viral infections.", "contents": "Immunopotentiation and antiviral chemotherapy in a suckling rat model of herpesvirus encephalitis. Encephalitis was induced in 10-day-old Wistar rats by intraperitoneal injection of approximately 100 50% tissue culture infective doses of herpes simplex virus type 2. Treatment regimens included immunopotentiation with levamisole and combined therapy with levamisole and an antiviral agent, adenine arabinoside. Rats treated with levamisole alone had significantly higher rates of survival than placebo-treated controls 14 days after injection of virus. Combination therapy with levamisole and adenine arabinoside prolonged survival, but there was no significant difference between treated animals and controls given placebo. Because adenine arabinoside inhibits the beneficial effect of levamisole in this model, antiviral chemotherapy in conjunction with immunopotentiation should be used with caution in humans. Further studies will be necessary to determine the value of immunopotentiation therapy in the treatment of life-threatening viral infections."} {"id": "PMID:180204", "title": "Experimental encephalitis caused by herpes simplex virus: comparison of treatment with tilorone hydrochloride and phosphonoacetic acid.", "content": "A mouse model of encephalitis caused by herpes simplex virus was used to compare the antiviral activity of tilorone hydrochloride with that of phosphonoacetic acid. These compounds were also administered simultaneously to determine whether the combination had a synergistic effect. Rates of survival and concentrations of virus in brain were used as criteria for judging the effectiveness of treatment. The fatal course of encephalitis was not altered by any treatment protocols in which tilorone hydrochloride was used alone. Four days of treatment with phosphonoacetic acid resulted in a long-term survival rate of about 15% of the infected, treated animals, and extension of this therapy for an additional three days resulted in an overall survival rate of about 35%. No increase in survival rate was obtained by use of phosphonoacetic acid and tilorone hydrochloride in combination. The concentration of virus in the brains of tilorone hydrochloride treated animals did not differ significantly from that in the untreated, infected control animals. Treatment with phosphonoacetic acid resulted in a reduction in titer of virus in brain and in an increased rate of survival.", "contents": "Experimental encephalitis caused by herpes simplex virus: comparison of treatment with tilorone hydrochloride and phosphonoacetic acid. A mouse model of encephalitis caused by herpes simplex virus was used to compare the antiviral activity of tilorone hydrochloride with that of phosphonoacetic acid. These compounds were also administered simultaneously to determine whether the combination had a synergistic effect. Rates of survival and concentrations of virus in brain were used as criteria for judging the effectiveness of treatment. The fatal course of encephalitis was not altered by any treatment protocols in which tilorone hydrochloride was used alone. Four days of treatment with phosphonoacetic acid resulted in a long-term survival rate of about 15% of the infected, treated animals, and extension of this therapy for an additional three days resulted in an overall survival rate of about 35%. No increase in survival rate was obtained by use of phosphonoacetic acid and tilorone hydrochloride in combination. The concentration of virus in the brains of tilorone hydrochloride treated animals did not differ significantly from that in the untreated, infected control animals. Treatment with phosphonoacetic acid resulted in a reduction in titer of virus in brain and in an increased rate of survival."} {"id": "PMID:180205", "title": "Intranasal challenge of mice with herpes simplex virus: an experimental model for evaluation of the efficacy of antiviral drugs.", "content": "An experimental model of herpetic infection based on intranasal challenge of 12-day-old mice with herpes simplex virus (type 1) has been developed for assessment of the efficacy of a variety of antiviral compounds with clinical potential: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, ribavirin, chloriteoxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and interferon. The model employed is reminiscent of herpetic encephalitis in humans in both the portal of entry (nasopharyngeal cavity) and the mode of transmission (nerve route) of the virus to the target organ (brain). The mortality rate from viral infection was significantly reduced (greater than or equal to 30%) by the following treatment regimens: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, and ribavirin, administered daily for seven consecutive days starting immediately after inoculation of virus, at dosage levels of 4-20 mg/kg, 20-100mg/kg, 100mg/kg, and 20-100 mg/kg, respectively; and chlorite-oxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and mouse interferon, administered 24 hr before viral challenge, as single doses of 100-500 mg/kg, 20mg/kg, and 10(7)-10(8) international reference units/kg respectively. Similar doses of polyriboinosinic-polyribocytidylic acid and mouse interferon administered after inoculation of virus did not alter the final mortality rate.", "contents": "Intranasal challenge of mice with herpes simplex virus: an experimental model for evaluation of the efficacy of antiviral drugs. An experimental model of herpetic infection based on intranasal challenge of 12-day-old mice with herpes simplex virus (type 1) has been developed for assessment of the efficacy of a variety of antiviral compounds with clinical potential: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, ribavirin, chloriteoxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and interferon. The model employed is reminiscent of herpetic encephalitis in humans in both the portal of entry (nasopharyngeal cavity) and the mode of transmission (nerve route) of the virus to the target organ (brain). The mortality rate from viral infection was significantly reduced (greater than or equal to 30%) by the following treatment regimens: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, and ribavirin, administered daily for seven consecutive days starting immediately after inoculation of virus, at dosage levels of 4-20 mg/kg, 20-100mg/kg, 100mg/kg, and 20-100 mg/kg, respectively; and chlorite-oxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and mouse interferon, administered 24 hr before viral challenge, as single doses of 100-500 mg/kg, 20mg/kg, and 10(7)-10(8) international reference units/kg respectively. Similar doses of polyriboinosinic-polyribocytidylic acid and mouse interferon administered after inoculation of virus did not alter the final mortality rate."} {"id": "PMID:180206", "title": "Effective antiviral chemotherapy in cytomegalovirus infection of mice.", "content": "Both murine and human strains of cytomegalovirus were shown to be sensitive to the antiviral effects of adenine arabinoside and phosphonoacetic acid in tissue culture. In mice with lethal cytomegalovirus infections, treatment with adenine arabinoside (either 500 mg/kg intraperitoneally once daily or 250 mg/kg intraperitoneally twice daily for seven days) failed to reduce the mortality rate or to decrease the mean number of days until death. In contrast, treatment with the same dosage regimen of phosphonoacetic acid significantly reduced the mortality rate and decreased the mean number of days until death even when therapy was delayed for 24 hr. Although early treatment with phosphonoacetic acid resulted in a marked reduction in viral titers in the brains and lungs of infected mice, the major reason for efficacy appeared to be complete inhibition of viral replication in the liver. The observation that titers of complement-requiring neutralizing antibody were significantly lower in treated animals than in untreated controls is further evidence of successful therapy. Treatment of a nonlethal cytomegalovirus infection with phosphonoacetic acid beginning 48 hr after viral challenge resulted in elimination of clinical signs of illness and reduction in viral titers in tissues. These results indicate that phosphonoacetic acid is successful in the treatment of murine infections with cytomegalovirus; they suggest that this drug should be considered for potential use in serious cytomegalovirus infections in humans.", "contents": "Effective antiviral chemotherapy in cytomegalovirus infection of mice. Both murine and human strains of cytomegalovirus were shown to be sensitive to the antiviral effects of adenine arabinoside and phosphonoacetic acid in tissue culture. In mice with lethal cytomegalovirus infections, treatment with adenine arabinoside (either 500 mg/kg intraperitoneally once daily or 250 mg/kg intraperitoneally twice daily for seven days) failed to reduce the mortality rate or to decrease the mean number of days until death. In contrast, treatment with the same dosage regimen of phosphonoacetic acid significantly reduced the mortality rate and decreased the mean number of days until death even when therapy was delayed for 24 hr. Although early treatment with phosphonoacetic acid resulted in a marked reduction in viral titers in the brains and lungs of infected mice, the major reason for efficacy appeared to be complete inhibition of viral replication in the liver. The observation that titers of complement-requiring neutralizing antibody were significantly lower in treated animals than in untreated controls is further evidence of successful therapy. Treatment of a nonlethal cytomegalovirus infection with phosphonoacetic acid beginning 48 hr after viral challenge resulted in elimination of clinical signs of illness and reduction in viral titers in tissues. These results indicate that phosphonoacetic acid is successful in the treatment of murine infections with cytomegalovirus; they suggest that this drug should be considered for potential use in serious cytomegalovirus infections in humans."} {"id": "PMID:180207", "title": "Prophylactic control of simian hemorrhagic fever in monkeys by an interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine.", "content": "A nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid containing poly-L-lysine and carboxymethylcellulose was used as prophylactic treatment of simian hemorrhagic fever in rhesus monkeys. This infection has proven uniformly fatal to more than 50 monkeys. Treatment 8 hr before infection and repeatedly thereafter completely prevented the development of viremia and death. Untreated animals died before development of antibodies to the virus. None of the treated animals developed antibody to the virus, a fact which suggested that viral growth was essentially completely blocked by the compound.", "contents": "Prophylactic control of simian hemorrhagic fever in monkeys by an interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine. A nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid containing poly-L-lysine and carboxymethylcellulose was used as prophylactic treatment of simian hemorrhagic fever in rhesus monkeys. This infection has proven uniformly fatal to more than 50 monkeys. Treatment 8 hr before infection and repeatedly thereafter completely prevented the development of viremia and death. Untreated animals died before development of antibodies to the virus. None of the treated animals developed antibody to the virus, a fact which suggested that viral growth was essentially completely blocked by the compound."} {"id": "PMID:180208", "title": "Measurements of the prevalence of viral infections.", "content": "Viral diseases exert their major impact through morbidity, impairment of personal health, loss of time at work and school, and cost of medical care. Relatively few of the known viruses cause a significant number of deaths; influenza, childhood viral pneumonia, and hepatitis are the only viral diseases causing more than 1,000 deaths per year. Data based on the National Health Interview Survey of the National Center for Health Statistics show that the common cold annually causes 35.6 acute illnesses per 100 persons. The data reported by the National Therapeutic Disease Index (on the basis of visits by patients to a sample of 1,500 private physicians) show that influenza and other acute respiratory conditions account for about one-third of all visits to physicians. Nearly all viruses first infect humans in infancy and childhood, with a relatively low fatality rate but with frequent episodes of illness.", "contents": "Measurements of the prevalence of viral infections. Viral diseases exert their major impact through morbidity, impairment of personal health, loss of time at work and school, and cost of medical care. Relatively few of the known viruses cause a significant number of deaths; influenza, childhood viral pneumonia, and hepatitis are the only viral diseases causing more than 1,000 deaths per year. Data based on the National Health Interview Survey of the National Center for Health Statistics show that the common cold annually causes 35.6 acute illnesses per 100 persons. The data reported by the National Therapeutic Disease Index (on the basis of visits by patients to a sample of 1,500 private physicians) show that influenza and other acute respiratory conditions account for about one-third of all visits to physicians. Nearly all viruses first infect humans in infancy and childhood, with a relatively low fatality rate but with frequent episodes of illness."} {"id": "PMID:180209", "title": "Persistence of the viral genome in interferon-treated cells infected with oncogneic or nononcogenic viruses.", "content": "In AKR mouse cells chronically infected with a murine leukemia virus, treatment with interferon for nine days resulted in sustained inhibition of extracellular production of murine leukemia virus but no inhibition of viral intracellular p30 antigen or of reverse transcriptase. Removal of interferon resulted in rapid reversal of these effects. Interferon-treated mouse L-cells were infected with high multiplicities of vesicular stomatitis virus or herpes simplex virus type 1. Infectious virus and intracellular viral antigen were rapidly eliminated from the interferon-treated cultures infected with herpes simplex virus. In cultures infected with vesicular stomatitis virus, titers of virus remained low in interferon-treated cells, but after about two weeks they rose rapidly and the cultures were destroyed. If treatment with interferon was reinstituted as late as nine days after primary infection, infectious vesicular stomatitis virus was eliminated, and there was no evidence for survival of the viral genome in these cultures. In the cultures infected with murine leukemia virus, inhibition of production of virus by treatment with interferon was possible, but the viral genome was not eliminated. In cells acutely infected with vesicular stomatitis virus or herpes simplex virus, however, the viral genomes were apparently eliminated from cultures treated with interferon.", "contents": "Persistence of the viral genome in interferon-treated cells infected with oncogneic or nononcogenic viruses. In AKR mouse cells chronically infected with a murine leukemia virus, treatment with interferon for nine days resulted in sustained inhibition of extracellular production of murine leukemia virus but no inhibition of viral intracellular p30 antigen or of reverse transcriptase. Removal of interferon resulted in rapid reversal of these effects. Interferon-treated mouse L-cells were infected with high multiplicities of vesicular stomatitis virus or herpes simplex virus type 1. Infectious virus and intracellular viral antigen were rapidly eliminated from the interferon-treated cultures infected with herpes simplex virus. In cultures infected with vesicular stomatitis virus, titers of virus remained low in interferon-treated cells, but after about two weeks they rose rapidly and the cultures were destroyed. If treatment with interferon was reinstituted as late as nine days after primary infection, infectious vesicular stomatitis virus was eliminated, and there was no evidence for survival of the viral genome in these cultures. In the cultures infected with murine leukemia virus, inhibition of production of virus by treatment with interferon was possible, but the viral genome was not eliminated. In cells acutely infected with vesicular stomatitis virus or herpes simplex virus, however, the viral genomes were apparently eliminated from cultures treated with interferon."} {"id": "PMID:180210", "title": "Influence of interferon on the synthesis of virus particles in oncornavirus carrier cell lines. IV. Relevance to the potential application of interferon in natural infectious diseases.", "content": "That interferon reduced the release of C-type oncornavirus particles by chronically infected mouse cells was shown by radiolabeling of the particles with uridine or amino acids and by determination of particle-associated reverse transcriptase. The number of released particles, as determined by direct electron microscopic enumeration, was reduced to a lesser extent. In contrast, interferon failed to affect the number of budding particles and caused a slight increase in the number of completed particles present in the microspace contiguous to the cell membranes. A working hypothesis is that, in the presence of interferon, C-type particle assembly and release are slowed but not arrested; sizable numbers of particles continue to be assembled and released. Some of these particles may be defective in one or more proteins, such as reverse transcriptase or proteins necessary for final release. These in vitro data justify speculation that, in vivo, interferon may be expected to reduce tissue damage due to antigen-antibody complex formation, but not damage due to sytolytic immune attack on cells carrying the antigens.", "contents": "Influence of interferon on the synthesis of virus particles in oncornavirus carrier cell lines. IV. Relevance to the potential application of interferon in natural infectious diseases. That interferon reduced the release of C-type oncornavirus particles by chronically infected mouse cells was shown by radiolabeling of the particles with uridine or amino acids and by determination of particle-associated reverse transcriptase. The number of released particles, as determined by direct electron microscopic enumeration, was reduced to a lesser extent. In contrast, interferon failed to affect the number of budding particles and caused a slight increase in the number of completed particles present in the microspace contiguous to the cell membranes. A working hypothesis is that, in the presence of interferon, C-type particle assembly and release are slowed but not arrested; sizable numbers of particles continue to be assembled and released. Some of these particles may be defective in one or more proteins, such as reverse transcriptase or proteins necessary for final release. These in vitro data justify speculation that, in vivo, interferon may be expected to reduce tissue damage due to antigen-antibody complex formation, but not damage due to sytolytic immune attack on cells carrying the antigens."} {"id": "PMID:180211", "title": "Localization fo the gene AVG for the antiviral expression of immune and classical interferon to the distal portion of the long arm of chromosome 21.", "content": "The responses of normal fibroblasts and of fibroblasts trisomic and monosomic for chromosome 21 to exogenously administered virus-induced (classical) and phytohemagglutinin-induced (immune) human interferon were determined. The virus-induced interferon was obtained from leukocytes treated with Sendai virus and from neonatal foreskin fibroblasts treated with Newcastle disease virus. With both classical and immune interferons, the mean response of the trisomic cell lines was three times that of the normal cells, whereas that of the monosomic lines was half or less that of the normal cells, Furthermore, a line trisomic for only the distal half of the long arm of chromosome 21 (q21 leads to qter) also demonstrated increased sensitivity to virus- and phytohemagglutinin-induced interferons, a fact that indicated that the gene responsible for the antiviral effect of interferon, AVG, is located on this part of chromosome 21. Responses to the two categories of interferon (virus-induced and phytohemagglutinin-induced) of individual cell lines of different degrees of sensitivity were strongly correlated (r=0.79). It is concluded, therefore, that despite their physical and antigenic differences, the antiviral expressions of both classical and immune interferons are ultimately mediated by the same genetic locus, AVG.", "contents": "Localization fo the gene AVG for the antiviral expression of immune and classical interferon to the distal portion of the long arm of chromosome 21. The responses of normal fibroblasts and of fibroblasts trisomic and monosomic for chromosome 21 to exogenously administered virus-induced (classical) and phytohemagglutinin-induced (immune) human interferon were determined. The virus-induced interferon was obtained from leukocytes treated with Sendai virus and from neonatal foreskin fibroblasts treated with Newcastle disease virus. With both classical and immune interferons, the mean response of the trisomic cell lines was three times that of the normal cells, whereas that of the monosomic lines was half or less that of the normal cells, Furthermore, a line trisomic for only the distal half of the long arm of chromosome 21 (q21 leads to qter) also demonstrated increased sensitivity to virus- and phytohemagglutinin-induced interferons, a fact that indicated that the gene responsible for the antiviral effect of interferon, AVG, is located on this part of chromosome 21. Responses to the two categories of interferon (virus-induced and phytohemagglutinin-induced) of individual cell lines of different degrees of sensitivity were strongly correlated (r=0.79). It is concluded, therefore, that despite their physical and antigenic differences, the antiviral expressions of both classical and immune interferons are ultimately mediated by the same genetic locus, AVG."} {"id": "PMID:180212", "title": "Advantages and limitations of animal models in the evaluation of antiviral substances.", "content": "Since many antiviral substances with potential for use in humans are in various phases of evaluation, criteria must be developed for selection of those compoinds with the greatest probability of efficacy and least toxicity. We lack background experience in evaluation of antivirals to permit extrapolation from in vitro tests to use in humans; it is of critical importance, therefore, to develop animal models for evaluation of antiviral substances before trials in humans and to establish guidelines for the relative predictive reliability of in vitro screening and evaluation in animal models. The complexity of drug-host and virus-host interaction and other factors may limit the predictive value of some or all experimental systems. Although the use of animal models is an important phase in the evaluation of antiviral chemotherapeutic agents, the models must be carefully studied and the interaction of drug and virus in the experimental animal specifically defined if optimal guidelines for the predictive value of model systems are to be developed. These guidelines must then be modified as experience is gained with antiviral substances that reach human trials.", "contents": "Advantages and limitations of animal models in the evaluation of antiviral substances. Since many antiviral substances with potential for use in humans are in various phases of evaluation, criteria must be developed for selection of those compoinds with the greatest probability of efficacy and least toxicity. We lack background experience in evaluation of antivirals to permit extrapolation from in vitro tests to use in humans; it is of critical importance, therefore, to develop animal models for evaluation of antiviral substances before trials in humans and to establish guidelines for the relative predictive reliability of in vitro screening and evaluation in animal models. The complexity of drug-host and virus-host interaction and other factors may limit the predictive value of some or all experimental systems. Although the use of animal models is an important phase in the evaluation of antiviral chemotherapeutic agents, the models must be carefully studied and the interaction of drug and virus in the experimental animal specifically defined if optimal guidelines for the predictive value of model systems are to be developed. These guidelines must then be modified as experience is gained with antiviral substances that reach human trials."} {"id": "PMID:180213", "title": "Aldosterone and renin-angiotensin responses to stimuli in patients with treated congestive heart failure.", "content": "Aldosterone responses to physiologic doses of known regulatory factors have been studied in 8 patients with treated congestive heart failure under standard conditions of electrolyte balance and controlled body posture. The response of plasma aldosterone, plasma renin activity (PRA), and in some instances angiotension II, to the brief (120 minute) intravenous administration of ACTH (1.25 mug beta1-24 ACTH in 60 minute and 5 mug in 60 minutes), angiotensin II (30 mug) and potassium (30 mEq.), and to 2 hours in the upright posture, was measured. The plasma aldosterone increase was greatest in response to ACTH (mean increment 20.8 ng. per 100 ml.) followed by that with upright posture (mean rise 17.1 ng. per 100 ml.), potassium (mean 6.7 ng. per 100 ml.) and angiotensin II (5.8 ng. per 100 ml.). PRA rose vigorously following 2 hours of upright posture and fell with angiotensin II infusion, but showed no definite change in response to potassium or ACTH. A diurnal pattern of PRA, angiotensin II, and plasma aldosterone on control days was observed in these patients, with higher prenoon levels falling to a nadir at midnight. The electrolyte and hormone response to administered aldosterone (75 mug over 2 hours) was also studied in the same patients. During aldosterone infusions, plasma aldosterone increased (increment range 36 to 110 ng. per 100 ml.), urine sodium excretion decreased, but no significant change in urine potassium excretion or in PRA was observed. It is concluded that small fluctuations in ACTH secretion, as well as change in body posture, produce marked effects on plasma aldosterone in patients with controlled congestive heart failure. Aldosterone responses to ACTH in these patients is similar to that observed in normal subjects.", "contents": "Aldosterone and renin-angiotensin responses to stimuli in patients with treated congestive heart failure. Aldosterone responses to physiologic doses of known regulatory factors have been studied in 8 patients with treated congestive heart failure under standard conditions of electrolyte balance and controlled body posture. The response of plasma aldosterone, plasma renin activity (PRA), and in some instances angiotension II, to the brief (120 minute) intravenous administration of ACTH (1.25 mug beta1-24 ACTH in 60 minute and 5 mug in 60 minutes), angiotensin II (30 mug) and potassium (30 mEq.), and to 2 hours in the upright posture, was measured. The plasma aldosterone increase was greatest in response to ACTH (mean increment 20.8 ng. per 100 ml.) followed by that with upright posture (mean rise 17.1 ng. per 100 ml.), potassium (mean 6.7 ng. per 100 ml.) and angiotensin II (5.8 ng. per 100 ml.). PRA rose vigorously following 2 hours of upright posture and fell with angiotensin II infusion, but showed no definite change in response to potassium or ACTH. A diurnal pattern of PRA, angiotensin II, and plasma aldosterone on control days was observed in these patients, with higher prenoon levels falling to a nadir at midnight. The electrolyte and hormone response to administered aldosterone (75 mug over 2 hours) was also studied in the same patients. During aldosterone infusions, plasma aldosterone increased (increment range 36 to 110 ng. per 100 ml.), urine sodium excretion decreased, but no significant change in urine potassium excretion or in PRA was observed. It is concluded that small fluctuations in ACTH secretion, as well as change in body posture, produce marked effects on plasma aldosterone in patients with controlled congestive heart failure. Aldosterone responses to ACTH in these patients is similar to that observed in normal subjects."} {"id": "PMID:180214", "title": "The process of cholesterol cholelithiasis induced by diet in the prairie dog: a physicochemical characterization.", "content": "The rapid induction of cholesterol cholelithiasis in a new experimental model, the prairie dog, has recently been reported by two groups. In this model they were able to induce gallstones in as brief a period as 2 weeks, using a 1.2 per cent cholesterol diet. This unprecedented time intensity or telescoping of the induction process provided a unique opportunity for observation of physicochemical changes occurring rapidly over a short period of time and to correlate these with degree of biliary cholesterol saturation. To make such observations, 97 adult male and female prairie dogs were used in the present study. Seventy-two were fed the high cholesterol diet and sacrificed at intervals over a 14-day period; the remaining 25 were used as controls. The primary objective of this work was to determine whether or not there was any relationship between the in vivo events induced in prairie dog bile and our recently reported detailed observations of cholesterol precipitation phenomena in synthetic bile analogs. In these studies, solutions of physiologically relevant composition were constructed, which, when plotted according to convention on a tri-linear graph, fell within the zone of metastable or suspended supersaturation. These solutions revealed a consistent and previously undescribed liquid crystal to solid crystal phase transition during their approach to equilibrium at 37 degrees C. The in vivo studies of prairie dog bile following rapid induction of supersaturation revealed identical changes. At first, the supersaturated biles were isotropic followed by a period of turbidity and invariable formation of mesophase. After a few days, the liquid crystals decreased and solid cholesterol crystallites appeared. The most striking aspect of these observations is that the in vitro work has now predicted not only static, but dynamic processes as well, with respect to cholesterol precipitation beginning with the metastably supersaturated state and eventuating in gallstone formation. Ancillary new findings, resulting from the high cholesterol diet, included the induction of human-like hyper-beta-lipoproteinemia and rapid hepatocyte degranulation shown by electron microscopy.", "contents": "The process of cholesterol cholelithiasis induced by diet in the prairie dog: a physicochemical characterization. The rapid induction of cholesterol cholelithiasis in a new experimental model, the prairie dog, has recently been reported by two groups. In this model they were able to induce gallstones in as brief a period as 2 weeks, using a 1.2 per cent cholesterol diet. This unprecedented time intensity or telescoping of the induction process provided a unique opportunity for observation of physicochemical changes occurring rapidly over a short period of time and to correlate these with degree of biliary cholesterol saturation. To make such observations, 97 adult male and female prairie dogs were used in the present study. Seventy-two were fed the high cholesterol diet and sacrificed at intervals over a 14-day period; the remaining 25 were used as controls. The primary objective of this work was to determine whether or not there was any relationship between the in vivo events induced in prairie dog bile and our recently reported detailed observations of cholesterol precipitation phenomena in synthetic bile analogs. In these studies, solutions of physiologically relevant composition were constructed, which, when plotted according to convention on a tri-linear graph, fell within the zone of metastable or suspended supersaturation. These solutions revealed a consistent and previously undescribed liquid crystal to solid crystal phase transition during their approach to equilibrium at 37 degrees C. The in vivo studies of prairie dog bile following rapid induction of supersaturation revealed identical changes. At first, the supersaturated biles were isotropic followed by a period of turbidity and invariable formation of mesophase. After a few days, the liquid crystals decreased and solid cholesterol crystallites appeared. The most striking aspect of these observations is that the in vitro work has now predicted not only static, but dynamic processes as well, with respect to cholesterol precipitation beginning with the metastably supersaturated state and eventuating in gallstone formation. Ancillary new findings, resulting from the high cholesterol diet, included the induction of human-like hyper-beta-lipoproteinemia and rapid hepatocyte degranulation shown by electron microscopy."} {"id": "PMID:180215", "title": "Evidence that the platelet retention factor is separate from the factor VIII-related antigen and factor VIII.", "content": "Plasmas from a pregnant patient with von Willebrand's disease and from a patient with von Willebrand's disease who is taking Premarin had elevated levels of Factor VIII-related antigen and Factor VIII activity without any improvement in their platelet retention abnormality. When these were added to the blood from nonpregnant patients with von Willebrand's disease no significant improvement in platelet retention followed. This suggests that the \"retention factor\" is independent of the antigenic Factor VIII-like material.", "contents": "Evidence that the platelet retention factor is separate from the factor VIII-related antigen and factor VIII. Plasmas from a pregnant patient with von Willebrand's disease and from a patient with von Willebrand's disease who is taking Premarin had elevated levels of Factor VIII-related antigen and Factor VIII activity without any improvement in their platelet retention abnormality. When these were added to the blood from nonpregnant patients with von Willebrand's disease no significant improvement in platelet retention followed. This suggests that the \"retention factor\" is independent of the antigenic Factor VIII-like material."} {"id": "PMID:180216", "title": "Regulation of plasma lecithin:cholesterol acyltransferase in man. I. Increased activity in primary hypertriglyceridemia.", "content": "Patients with primary hypertriglyceridemia have been reported to manifest increased in vivo turnover of plasma cholesteryl esters. To ascertain if this is due to plasma lecithin:cholesterol acyltransferase (LCAT) and to explore a possible link between triglyceride and cholesteryl ester turnover, we have measured LCAT in 15 patients with Type IV, 2 with Type V, 1 with Type III, and 9 with Type II B hyperlipoproteinemia. LCAT was significantly elevated (p less than 0.001) in hypertriglyceridemic subjects, regardless of lipoprotein pattern. In the Type IV group, but not in normal subjects, LCAT correlated significantly with measures of very low-density lipoprotein (VLDL) elevation, including plasma triglycerides and particularly VLDL-unesterified cholesterol, but not with body weight or substrate high-density lipoprotein (HDL) lipid levels. On repeated determinations in individual subjects, a relationship between triglyceride fluctuations and LCAT could be demonstrated in only one subject over an extreme range of triglyceride levels. Analysis of lipoprotein lipids revealed that the ester:free cholesterol ratio in VLDL was increased in hypertriglyceridemia, but was not correlated with enzyme level. In vitro removal of endogenous VLDL or addition of VLDL from lipemic plasmas to normal plasmas was without effect on enzyme activity. Regulation of enzyme activity does not appear to be a direct function of VLDL level.", "contents": "Regulation of plasma lecithin:cholesterol acyltransferase in man. I. Increased activity in primary hypertriglyceridemia. Patients with primary hypertriglyceridemia have been reported to manifest increased in vivo turnover of plasma cholesteryl esters. To ascertain if this is due to plasma lecithin:cholesterol acyltransferase (LCAT) and to explore a possible link between triglyceride and cholesteryl ester turnover, we have measured LCAT in 15 patients with Type IV, 2 with Type V, 1 with Type III, and 9 with Type II B hyperlipoproteinemia. LCAT was significantly elevated (p less than 0.001) in hypertriglyceridemic subjects, regardless of lipoprotein pattern. In the Type IV group, but not in normal subjects, LCAT correlated significantly with measures of very low-density lipoprotein (VLDL) elevation, including plasma triglycerides and particularly VLDL-unesterified cholesterol, but not with body weight or substrate high-density lipoprotein (HDL) lipid levels. On repeated determinations in individual subjects, a relationship between triglyceride fluctuations and LCAT could be demonstrated in only one subject over an extreme range of triglyceride levels. Analysis of lipoprotein lipids revealed that the ester:free cholesterol ratio in VLDL was increased in hypertriglyceridemia, but was not correlated with enzyme level. In vitro removal of endogenous VLDL or addition of VLDL from lipemic plasmas to normal plasmas was without effect on enzyme activity. Regulation of enzyme activity does not appear to be a direct function of VLDL level."} {"id": "PMID:180217", "title": "Catabolism of canine apolipoprotein A-I: purification, catabolic rate, organs of catabolism, and the liver subcellular catabolic site.", "content": "The catabolic site(s) of plasma lipoproteins and apolipoproteins has not been established. We have purified one of the major apolipoproteins and explored its catabolic rate and its site of catabolism. Apolipoprotein (Apo) A-1 was purified by column chromatography of canine high-density lipoprotein (HDL) subfraction, HDL3, which was totally delipidated; the purified Apo A-1, molecular weight 28,000, had only one precipitin line to either anti-Apo A-1, or anti-Apo HDL3 serum. Apo A-I was then iodinated, its catabolic rate measured, and the various organs and the subcellular sites of liver involved in the catabolism were investigated. The T 1/2 of 125I-Apo A-I in HDL3 was 3.33 +/- 0.08 days and in plasma 3.52 +/- 0.17 days. The disappearance curve of radioactivity recovered in density fractions d less than 1.110 and d greater than 1.210 Gm. per milliliter was the same as that in HDL3, suggesting identical Apo A-I catabolism in each density class. The liver and kidney absorbed more radioactivity than did the spleen, heart, lung, and intestine. In subcellular fractions of liver, radioactivity was predominantly recovered in the light mitochondrial fraction. There was a statistically significant correlation between the acid phosphatase relative specific activity and the relative specific radioactivity in each subcellular fraction examined at several time intervals after the injection of 125I-Apo A-I. Direct organelle isolation and demonstration of labeled apoplipoprotein uptake indicate that liver lysosomes may play an important role in the catabolism of Apo A-I, as may those of the kidney.", "contents": "Catabolism of canine apolipoprotein A-I: purification, catabolic rate, organs of catabolism, and the liver subcellular catabolic site. The catabolic site(s) of plasma lipoproteins and apolipoproteins has not been established. We have purified one of the major apolipoproteins and explored its catabolic rate and its site of catabolism. Apolipoprotein (Apo) A-1 was purified by column chromatography of canine high-density lipoprotein (HDL) subfraction, HDL3, which was totally delipidated; the purified Apo A-1, molecular weight 28,000, had only one precipitin line to either anti-Apo A-1, or anti-Apo HDL3 serum. Apo A-I was then iodinated, its catabolic rate measured, and the various organs and the subcellular sites of liver involved in the catabolism were investigated. The T 1/2 of 125I-Apo A-I in HDL3 was 3.33 +/- 0.08 days and in plasma 3.52 +/- 0.17 days. The disappearance curve of radioactivity recovered in density fractions d less than 1.110 and d greater than 1.210 Gm. per milliliter was the same as that in HDL3, suggesting identical Apo A-I catabolism in each density class. The liver and kidney absorbed more radioactivity than did the spleen, heart, lung, and intestine. In subcellular fractions of liver, radioactivity was predominantly recovered in the light mitochondrial fraction. There was a statistically significant correlation between the acid phosphatase relative specific activity and the relative specific radioactivity in each subcellular fraction examined at several time intervals after the injection of 125I-Apo A-I. Direct organelle isolation and demonstration of labeled apoplipoprotein uptake indicate that liver lysosomes may play an important role in the catabolism of Apo A-I, as may those of the kidney."} {"id": "PMID:180218", "title": "Benign mixed tumour of heterotopic salivary gland tissue in upper neck. Report of a case with a review of the literature on heterotopic salivary gland tissue.", "content": "A case of benign mixed tumour arising in ectopic salivary gland tissue of the mucous type is described. The tumour was located at the angle of the right mandible, in the upper middle third of the neck, along the anterior border of the sternomastoid muscle. This observation is substantiated by a pathomorphological study. A comprehensive review of the world literature on heteroptic salivary gland tissue has also been carried out, together with a search of the possible pathogenesis which seems to be connected with an anomalous embryonic development within the branchial apparatus.", "contents": "Benign mixed tumour of heterotopic salivary gland tissue in upper neck. Report of a case with a review of the literature on heterotopic salivary gland tissue. A case of benign mixed tumour arising in ectopic salivary gland tissue of the mucous type is described. The tumour was located at the angle of the right mandible, in the upper middle third of the neck, along the anterior border of the sternomastoid muscle. This observation is substantiated by a pathomorphological study. A comprehensive review of the world literature on heteroptic salivary gland tissue has also been carried out, together with a search of the possible pathogenesis which seems to be connected with an anomalous embryonic development within the branchial apparatus."} {"id": "PMID:180219", "title": "Measurement of two plasma triglyceride lipases by an immunochemical method: studies in patients with hypertriglyceridemia.", "content": "Postheparin plasma lipolytic activity consists of two hydrolytic activities, hepatic triglyceride lipase and lipoprotein lipase. These two enzymes were separated and partially purified by means of ammonium sulfate precipitation and affinity chromatography using Sepharose with covalently linked heparin and concanavalin A, respectively. Antibodies were produced against hepatic triglyceride lipase and they did not cross react with lipoprotein lipase. Optimal conditions for selective precipitation of hepatic lipase and specific measurement of these two lipases were investigated. This method was applied to the study of 15 patients with hypertriglyceridemia and 8 patients with familial lecithin-cholesterol-acyltransferase deficiency of whom 6 also had a marked elevated plasma triglyceride concentration. All patients had normal values of hepatic plasma lipase. All 8 patients with Type I and 2 of 4 patients with Type V hyperlipoproteinemia had lipoprotein lipase activities that were markedly reduced. The patients with Type III hyperlipoproteinemia and all 8 patients with lecithin-cholesterol-acyltransferase deficiency also had normal lipoprotein lipase values. These studies emphasize the necessity for differentiating between triglyceride lipase activity of hepatic and extrahepatic origin in evaluating patients with impaired triglyceride metabolism.", "contents": "Measurement of two plasma triglyceride lipases by an immunochemical method: studies in patients with hypertriglyceridemia. Postheparin plasma lipolytic activity consists of two hydrolytic activities, hepatic triglyceride lipase and lipoprotein lipase. These two enzymes were separated and partially purified by means of ammonium sulfate precipitation and affinity chromatography using Sepharose with covalently linked heparin and concanavalin A, respectively. Antibodies were produced against hepatic triglyceride lipase and they did not cross react with lipoprotein lipase. Optimal conditions for selective precipitation of hepatic lipase and specific measurement of these two lipases were investigated. This method was applied to the study of 15 patients with hypertriglyceridemia and 8 patients with familial lecithin-cholesterol-acyltransferase deficiency of whom 6 also had a marked elevated plasma triglyceride concentration. All patients had normal values of hepatic plasma lipase. All 8 patients with Type I and 2 of 4 patients with Type V hyperlipoproteinemia had lipoprotein lipase activities that were markedly reduced. The patients with Type III hyperlipoproteinemia and all 8 patients with lecithin-cholesterol-acyltransferase deficiency also had normal lipoprotein lipase values. These studies emphasize the necessity for differentiating between triglyceride lipase activity of hepatic and extrahepatic origin in evaluating patients with impaired triglyceride metabolism."} {"id": "PMID:180220", "title": "Mechanism of salt-mediated inhibition of lipoprotein lipase.", "content": "The activity of lipoprotein lipase isolated from rat postheparin plasma has been determined with synthetic lipids, in the presence and absence of apoprotein of the natural substrate very low density lipoprotein, as a function of medium ion-pair concentration of a number of different inorganic salts. The several kinetic effects of lipoprotein protein on lipase activity were specifically and quantitatively reversed in the presence of molar sodium chloride or solutions of equivalent effective ion concentrations of other salts. Salt-mediated inhibition was fully reversible by silution and was independent of substrate concentration. Inhibition was a function of the identity of the salt anion within a Hofmeister (lyotropic) series: I- greater than SCN- greater than NO3- greater than Cl- greater than F-, and, in these terms, was not significantly different for a series of inorganic chlorides (Li+, Na+, K+, Cs+). The effects of salts on the natural lipoprotein substrates, chylomicrons, and very low density lipoproteins were similar to those obtained with a synthetic lipid-protein substrate complex. These findings are discussed in the light of recent ideas on the activation of lipoprotein lipase.", "contents": "Mechanism of salt-mediated inhibition of lipoprotein lipase. The activity of lipoprotein lipase isolated from rat postheparin plasma has been determined with synthetic lipids, in the presence and absence of apoprotein of the natural substrate very low density lipoprotein, as a function of medium ion-pair concentration of a number of different inorganic salts. The several kinetic effects of lipoprotein protein on lipase activity were specifically and quantitatively reversed in the presence of molar sodium chloride or solutions of equivalent effective ion concentrations of other salts. Salt-mediated inhibition was fully reversible by silution and was independent of substrate concentration. Inhibition was a function of the identity of the salt anion within a Hofmeister (lyotropic) series: I- greater than SCN- greater than NO3- greater than Cl- greater than F-, and, in these terms, was not significantly different for a series of inorganic chlorides (Li+, Na+, K+, Cs+). The effects of salts on the natural lipoprotein substrates, chylomicrons, and very low density lipoproteins were similar to those obtained with a synthetic lipid-protein substrate complex. These findings are discussed in the light of recent ideas on the activation of lipoprotein lipase."} {"id": "PMID:180221", "title": "Phosphatidylglycerol in lung surfactant. III. Possible modifier of surfactant function.", "content": "Lamellar bodies and alveolar lavage from adult mammalian lung contain unusually high concentrations of phosphatidylglycerol that could serve as a sensitive indicator of surfactant. Phosphatidylglycerol was absent and phosphatidylinositol was correspondingly prominent in surfactant from the preterm rabbit fetus. Phosphatidylglycerol rapidly appeared and phosphatidylinositol decreased following the delivery. Surfactant isolated from the prematurely born rabbit or from humans with respiratory distress syndrome never contained phosphatidylglycerol. Comparison between lamellar bodies from fetal and postnatal rabbits revealed remarkably similar composition except for the acidic phospholipids; however, the physico-chemical properties were different. The compressibility of the surface film (i.e. the ratio of the fractional decrease in surface area and the corresponding decrease in surface tension) at low surface tensions was higher with fetal than with postnatal surfactant, whereas the difference in minimum surface tensions was small. These data suggest that phosphatidylglycerol is not an essential component required for the formation of the complex, but it improves the properties of surfactant in stabilizing the alveoli.", "contents": "Phosphatidylglycerol in lung surfactant. III. Possible modifier of surfactant function. Lamellar bodies and alveolar lavage from adult mammalian lung contain unusually high concentrations of phosphatidylglycerol that could serve as a sensitive indicator of surfactant. Phosphatidylglycerol was absent and phosphatidylinositol was correspondingly prominent in surfactant from the preterm rabbit fetus. Phosphatidylglycerol rapidly appeared and phosphatidylinositol decreased following the delivery. Surfactant isolated from the prematurely born rabbit or from humans with respiratory distress syndrome never contained phosphatidylglycerol. Comparison between lamellar bodies from fetal and postnatal rabbits revealed remarkably similar composition except for the acidic phospholipids; however, the physico-chemical properties were different. The compressibility of the surface film (i.e. the ratio of the fractional decrease in surface area and the corresponding decrease in surface tension) at low surface tensions was higher with fetal than with postnatal surfactant, whereas the difference in minimum surface tensions was small. These data suggest that phosphatidylglycerol is not an essential component required for the formation of the complex, but it improves the properties of surfactant in stabilizing the alveoli."} {"id": "PMID:180222", "title": "Gas-liquid chromatography of bile acids: a new liquid phase for both acetate and trimethylsilyl derivatives.", "content": "Polymetaphenoxylene (PPE-20) has been found to be more useful than cyclohexane dimethanol succinate (HI-EFF-8-BP) for trimethylsilyl derivatives of bile acids and to be preferable to trifluoropropyl substituted silicone (OV-210, QF-1) for analysis of their acetate derivatives.", "contents": "Gas-liquid chromatography of bile acids: a new liquid phase for both acetate and trimethylsilyl derivatives. Polymetaphenoxylene (PPE-20) has been found to be more useful than cyclohexane dimethanol succinate (HI-EFF-8-BP) for trimethylsilyl derivatives of bile acids and to be preferable to trifluoropropyl substituted silicone (OV-210, QF-1) for analysis of their acetate derivatives."} {"id": "PMID:180223", "title": "Study of the effect of ACTH and cortisol on the plasms lipids in man using thin-layer chromatography.", "content": "This is a study of the action of ACTH and cortisol on plasma lipids using thin-layer chromatography and evaluation by densitometry. We have studied the action of 50 I.U. of ACTH in eight healthy individuals. We found an increase of free fatty acids after four hours and of triglycerides and esterified cholesterol after six hours. Free cholesterol levels declined after another six hours, the decrease becoming more intense after twenty-four hours. After twenty-four hours lecithin underwent a decline which is accompanied by an increase of lisolecithin. There was a decrease in the total amount of phospholipids. Seven patients received 100 mg. of cortisol intravenously over a period of ten minutes. We obtained an increase in free fatty acids after four hours and an increase of cholesterol after half and hour. We concluded that ACTH activates peripheral lipolysis thereby facilitating the hepatic synthesis of triglycerides and that it exerts a stimulating action on the lecithin-cholesterol-acyl-transferase system. Cortisol acts by facilitating the synthesis of triglycerides in the liver and increasing the hydrolysis of triglycerides in the plasma.", "contents": "Study of the effect of ACTH and cortisol on the plasms lipids in man using thin-layer chromatography. This is a study of the action of ACTH and cortisol on plasma lipids using thin-layer chromatography and evaluation by densitometry. We have studied the action of 50 I.U. of ACTH in eight healthy individuals. We found an increase of free fatty acids after four hours and of triglycerides and esterified cholesterol after six hours. Free cholesterol levels declined after another six hours, the decrease becoming more intense after twenty-four hours. After twenty-four hours lecithin underwent a decline which is accompanied by an increase of lisolecithin. There was a decrease in the total amount of phospholipids. Seven patients received 100 mg. of cortisol intravenously over a period of ten minutes. We obtained an increase in free fatty acids after four hours and an increase of cholesterol after half and hour. We concluded that ACTH activates peripheral lipolysis thereby facilitating the hepatic synthesis of triglycerides and that it exerts a stimulating action on the lecithin-cholesterol-acyl-transferase system. Cortisol acts by facilitating the synthesis of triglycerides in the liver and increasing the hydrolysis of triglycerides in the plasma."} {"id": "PMID:180225", "title": "Changes in adrenocortical function in male and female guinea-pigs during maturation.", "content": "Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs.", "contents": "Changes in adrenocortical function in male and female guinea-pigs during maturation. Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs."} {"id": "PMID:180226", "title": "Endocrine and environmental influences upon plasma cortisol concentrations and plasma renin activity of the eel, Anguilla anguilla L.", "content": "The plasma concentrations of cortisol, sodium, potassium and calcium and plasma osmolarity were determined in freshwater silver eels, after intravascular injections of eel renin preparations, mammalian ACTH, mammalian angiotensin II and eel muscle extracts. Arterial blood specimens were taken before and after injection of test substances. Partially purified eel and rat renal renins gave prolonged pressor responses in intact and hypophysectomized eels and in the nephrectomized rat anaesthetized with sodium pentobarbitone. Angiotensin, but not ACTH, produced obvious pressor responses in intact and hypophysectomized eels and in eels without their corpuscles of Stannius. Hypophysectomized eels 4-8 days after operation had reduced plasma cortisol concentrations. No change in cortisol occurred in eels after removal of the corpuscles of Stannius. Eel renin preparations and ACTH gave increased concentrations of plasma cortisol 30 min after injection into hypophysectomized and intact eels. In general, the length of the renin-generated pressor response and the increased cortisol concentration were concomitant occurrences. Angiotensin injected into eels with corpuscles of Stannius removed and into hypophysectomized eels also increased cortisol levels. Control muscle extracts produced no significant changes. There were no acute changes in plasma electrolyte concentrations after the injections. Plasma renin activity measured indirectly by bioassay of angiotensin generated in vitro was more than twice as great in eels adapted to seawater than in eels in fresh water. Plasma renin activity gradually fell when eels were transferred from seawater to fresh water, and increased when the reverse transfer was carried out.", "contents": "Endocrine and environmental influences upon plasma cortisol concentrations and plasma renin activity of the eel, Anguilla anguilla L. The plasma concentrations of cortisol, sodium, potassium and calcium and plasma osmolarity were determined in freshwater silver eels, after intravascular injections of eel renin preparations, mammalian ACTH, mammalian angiotensin II and eel muscle extracts. Arterial blood specimens were taken before and after injection of test substances. Partially purified eel and rat renal renins gave prolonged pressor responses in intact and hypophysectomized eels and in the nephrectomized rat anaesthetized with sodium pentobarbitone. Angiotensin, but not ACTH, produced obvious pressor responses in intact and hypophysectomized eels and in eels without their corpuscles of Stannius. Hypophysectomized eels 4-8 days after operation had reduced plasma cortisol concentrations. No change in cortisol occurred in eels after removal of the corpuscles of Stannius. Eel renin preparations and ACTH gave increased concentrations of plasma cortisol 30 min after injection into hypophysectomized and intact eels. In general, the length of the renin-generated pressor response and the increased cortisol concentration were concomitant occurrences. Angiotensin injected into eels with corpuscles of Stannius removed and into hypophysectomized eels also increased cortisol levels. Control muscle extracts produced no significant changes. There were no acute changes in plasma electrolyte concentrations after the injections. Plasma renin activity measured indirectly by bioassay of angiotensin generated in vitro was more than twice as great in eels adapted to seawater than in eels in fresh water. Plasma renin activity gradually fell when eels were transferred from seawater to fresh water, and increased when the reverse transfer was carried out."} {"id": "PMID:180227", "title": "Active transport of sodium by the malpighian tubules of the tsetse fly Glossian morsitans.", "content": "Isolated Malpighian tubules of Glossina morsitans are able to transport sodium against its concentration gradient. Their rate of secretion is dependent on the sodium concentration of the bathing medium. Potassium must be present in the bathing solution for rapid secretion to be maintained, but it does not play an active role in fluid secretion. Lithium and ammonium ions are able to substitute partially for sodium, other monovalent cations cannot. Ouabain does not affect rapid secretion by Glossina tubules in vitro. Conclusions drawn from the results are incorporated into a model of Malpighian tubule cell function in this insect.", "contents": "Active transport of sodium by the malpighian tubules of the tsetse fly Glossian morsitans. Isolated Malpighian tubules of Glossina morsitans are able to transport sodium against its concentration gradient. Their rate of secretion is dependent on the sodium concentration of the bathing medium. Potassium must be present in the bathing solution for rapid secretion to be maintained, but it does not play an active role in fluid secretion. Lithium and ammonium ions are able to substitute partially for sodium, other monovalent cations cannot. Ouabain does not affect rapid secretion by Glossina tubules in vitro. Conclusions drawn from the results are incorporated into a model of Malpighian tubule cell function in this insect."} {"id": "PMID:180228", "title": "The influence of various factors on fluid secretion by in vitro salivary glands of ixodid Ticks.", "content": "1. Salivary glands of the female ixodid tick, Dermacentor andersoni, secrete fluid in vitro when bathed in a slightly modified version of the mammalian tissue culture medium 'TC 199'. 2. Rate of salivation in vitro increases with progression of feeding, but there is no comparable increase in dry weight of the salivary glands during the early phase of engorgement. Engorged ticks secreted at only 25% the rate of 90-250 mg ticks, indicating that salivary gland degeneration has already begun in the very early post-engorgement stage. 3. A salivary gland stimulating factor can be detected in the nervous system but not in other tissues. 4. Male salivary glands secrete at only 1/20th the rate of female glands. Thus males probably do not use their salivary glands as osmoregulatory organs. 5. From the uniform lack of response to ACh and uniform response to DA in 7 ixodid tick species, it is suggested that the control of salivation is similar throughout the ixodid family.", "contents": "The influence of various factors on fluid secretion by in vitro salivary glands of ixodid Ticks. 1. Salivary glands of the female ixodid tick, Dermacentor andersoni, secrete fluid in vitro when bathed in a slightly modified version of the mammalian tissue culture medium 'TC 199'. 2. Rate of salivation in vitro increases with progression of feeding, but there is no comparable increase in dry weight of the salivary glands during the early phase of engorgement. Engorged ticks secreted at only 25% the rate of 90-250 mg ticks, indicating that salivary gland degeneration has already begun in the very early post-engorgement stage. 3. A salivary gland stimulating factor can be detected in the nervous system but not in other tissues. 4. Male salivary glands secrete at only 1/20th the rate of female glands. Thus males probably do not use their salivary glands as osmoregulatory organs. 5. From the uniform lack of response to ACh and uniform response to DA in 7 ixodid tick species, it is suggested that the control of salivation is similar throughout the ixodid family."} {"id": "PMID:180229", "title": "Age-related changes in cell surface antigens of preleukemic AKR thymocytes.", "content": "Thymocytes from preleukemic AKR mice aged 5-6 mo have an altered pattern of cell surface antigens. The expression of four MuLV-related antigens on the cell surface (GIX, GCSA, gp70, p30) is markedly increased in comparison to 2-mo-old AKR mice and approximates the heightened levels of these antigens found on thymic leukemia cells. H-2 and Thy-1 alloantigens also show characteristic modifications in relation to age and leukemia development. In contrast to the high Thy-1/low H-2 levels on 2-mo-old AKR thymocytes, thymocytes from 6-mo-old mice and thymic leukemia cells frequently show a low Thy-1/high H-2 surface phenotype. As thymocytes from mouse strains with a low incidence of leukemia do not show these changes, they appear to represent a stage in the conversion of normal cells to leukemia cells.", "contents": "Age-related changes in cell surface antigens of preleukemic AKR thymocytes. Thymocytes from preleukemic AKR mice aged 5-6 mo have an altered pattern of cell surface antigens. The expression of four MuLV-related antigens on the cell surface (GIX, GCSA, gp70, p30) is markedly increased in comparison to 2-mo-old AKR mice and approximates the heightened levels of these antigens found on thymic leukemia cells. H-2 and Thy-1 alloantigens also show characteristic modifications in relation to age and leukemia development. In contrast to the high Thy-1/low H-2 levels on 2-mo-old AKR thymocytes, thymocytes from 6-mo-old mice and thymic leukemia cells frequently show a low Thy-1/high H-2 surface phenotype. As thymocytes from mouse strains with a low incidence of leukemia do not show these changes, they appear to represent a stage in the conversion of normal cells to leukemia cells."} {"id": "PMID:180230", "title": "[Enzyme kinetic determination of glucose (author's transl)].", "content": "A reaction kinetic method is described for the determination of glucose in biological fluids. Glucose is oxidized to gluconic acid and NAD is reduced to NADH in the presence of glucose dehydrogenase. The rate of formation of NADH is followed in a LKB Reaction-Rate-Meter. Together with the analogue read-out, the rate of reaction is determined with a newly developed kinetic calculator. The specifications of the calculator are given. The new method has the advantage of a high rate of throughput and good reproducibility.", "contents": "[Enzyme kinetic determination of glucose (author's transl)]. A reaction kinetic method is described for the determination of glucose in biological fluids. Glucose is oxidized to gluconic acid and NAD is reduced to NADH in the presence of glucose dehydrogenase. The rate of formation of NADH is followed in a LKB Reaction-Rate-Meter. Together with the analogue read-out, the rate of reaction is determined with a newly developed kinetic calculator. The specifications of the calculator are given. The new method has the advantage of a high rate of throughput and good reproducibility."} {"id": "PMID:180231", "title": "[Stabilization of reduced beta-nicotinamide-adenine-dinucleotide in an organic solvent (author's transl)].", "content": "NADH is surprisingly stable, providing it is stored in anhydrous organic solvents, and not, as hitherto, in aqueous solvents. The stability of NADH was investigated in solution in ethylene glycol-Tris over a period of 136 days at temperatures of 2-8 degrees C, 19-22 degrees C, 35 degrees C, 45 degrees C and 60 degrees C. For comparison, the stability of NADH in solution in distilled water was studied under similar conditions.", "contents": "[Stabilization of reduced beta-nicotinamide-adenine-dinucleotide in an organic solvent (author's transl)]. NADH is surprisingly stable, providing it is stored in anhydrous organic solvents, and not, as hitherto, in aqueous solvents. The stability of NADH was investigated in solution in ethylene glycol-Tris over a period of 136 days at temperatures of 2-8 degrees C, 19-22 degrees C, 35 degrees C, 45 degrees C and 60 degrees C. For comparison, the stability of NADH in solution in distilled water was studied under similar conditions."} {"id": "PMID:180232", "title": "A kinetic method for serum 5'-nucleotidase using stabilised glutamate dehydrogenase.", "content": "A modification of a kinetic determination of 5'-nucleotidase (EC 3.1.3.5) activity is described. Special attention has been paid to the stabilisation of glutamate dehydrogenase (EC 1.4.1.2) by L-leucine, optimal NADH concentration and the influence of endogeneous ammonia. The optimal concentrations of the other constituents of the reagent were checked with the optimal values given in the literature. Normal values were determined. The proposed method shows a good correlation with a colorimetric reference method.", "contents": "A kinetic method for serum 5'-nucleotidase using stabilised glutamate dehydrogenase. A modification of a kinetic determination of 5'-nucleotidase (EC 3.1.3.5) activity is described. Special attention has been paid to the stabilisation of glutamate dehydrogenase (EC 1.4.1.2) by L-leucine, optimal NADH concentration and the influence of endogeneous ammonia. The optimal concentrations of the other constituents of the reagent were checked with the optimal values given in the literature. Normal values were determined. The proposed method shows a good correlation with a colorimetric reference method."} {"id": "PMID:180233", "title": "Adenosine 3',5'-monophosphate, morphogenetic movements and embryonic neural differentiation in Pleurodeles waltlii.", "content": "Evidence is presented for the following hypothesis dealing with dibutyryl-c-AMP induction of neural differentiation in Pleurodeles waltlii embryos: (1) Dibutyryl-c-AMP induces the determination for neural differentiation. (2) Additional dibutyryl-c-AMP is not needed for cytodifferentiation. (3) Cytodifferentiation of induced cells can only take place after morphogenetic movements (in vivo) or extensive cell migrations (in vitro). It is suggested that cell migrations, both in vivo and in vitro, lead to the separation of the induced cells from one another or from unidentified inhibitory cells.", "contents": "Adenosine 3',5'-monophosphate, morphogenetic movements and embryonic neural differentiation in Pleurodeles waltlii. Evidence is presented for the following hypothesis dealing with dibutyryl-c-AMP induction of neural differentiation in Pleurodeles waltlii embryos: (1) Dibutyryl-c-AMP induces the determination for neural differentiation. (2) Additional dibutyryl-c-AMP is not needed for cytodifferentiation. (3) Cytodifferentiation of induced cells can only take place after morphogenetic movements (in vivo) or extensive cell migrations (in vitro). It is suggested that cell migrations, both in vivo and in vitro, lead to the separation of the induced cells from one another or from unidentified inhibitory cells."} {"id": "PMID:180234", "title": "Distribution of cytochrome-like respiration in streptococci.", "content": "The electron transport systems of 134 strains of streptococci were studied after aerobic growth on glucose in the presence of haematin, by examining the inhibition of electron transport as well as the cellular site of NADH oxidation. Each strain was placed into one of three possible groups: cytochrome-like NADH oxidase; flavin-like NADH oxidase; or no NADH oxidase. Most (88%) of the strains of Streptococcus faecalis and its variants liquefaciens and zymogenes and a few strains of S. lactis and its variant diacetylactis contained cytochrome-like respiratory systems. Other streptococci including S. faecium fell into one of the other groups but did not contain cytochrome-like NADH oxidases.", "contents": "Distribution of cytochrome-like respiration in streptococci. The electron transport systems of 134 strains of streptococci were studied after aerobic growth on glucose in the presence of haematin, by examining the inhibition of electron transport as well as the cellular site of NADH oxidation. Each strain was placed into one of three possible groups: cytochrome-like NADH oxidase; flavin-like NADH oxidase; or no NADH oxidase. Most (88%) of the strains of Streptococcus faecalis and its variants liquefaciens and zymogenes and a few strains of S. lactis and its variant diacetylactis contained cytochrome-like respiratory systems. Other streptococci including S. faecium fell into one of the other groups but did not contain cytochrome-like NADH oxidases."} {"id": "PMID:180235", "title": "Fractionation by differential and zonal centrifugation of spheroplasts prepared from a glucose-repressed fission yeast Schizosaccharomyces pombe 972h-.", "content": "A method is described for the preparation of spheroplasts in high yield from Schizosaccharomyces pombe, by treating cells grown in the presence of glucose and deoxyglucose with snail digestive enzymes. Gentle disruption of such spheroplasts yielded homogenates, from which marker enzymes for nuclei (NAD pyrophosphorylase) and mitochondria (cytochrome c oxidase activity and spectroscopically-detectable cytochromes a + a3) could be quantitatively sedimented by low-speed centrifugation. In contrast to previous findings with Saccharomyces carlsbergensis, cytochrome c oxidase and another mitochondrial enzyme, succinate dehydrogenase, were completely sedimentable by zonal centrifugation in sucrose gradients in the presence of either 2 mM-MgCl2 or 0-4 mM-EDTA. Mitochondria were apparently smaller and of lower buoyant density in gradients containing EDTA. The bulk of the total units of malate dehydrogenase and NADH; cytochrome c oxidoreductase sedimented with mitochondria, whereas NADPH: cytochrome c oxidoreductase was located in fractions containing no mitochondria. The distributions of mitochondrial enzymes were heterogeneous in populations of mitochondria separated on the basis of size or density. The possible origins of mitochondrial heterogeneity in extracts of S. pombe are discussed with special reference to changes in the enzyme activities of cells during the cell cycle.", "contents": "Fractionation by differential and zonal centrifugation of spheroplasts prepared from a glucose-repressed fission yeast Schizosaccharomyces pombe 972h-. A method is described for the preparation of spheroplasts in high yield from Schizosaccharomyces pombe, by treating cells grown in the presence of glucose and deoxyglucose with snail digestive enzymes. Gentle disruption of such spheroplasts yielded homogenates, from which marker enzymes for nuclei (NAD pyrophosphorylase) and mitochondria (cytochrome c oxidase activity and spectroscopically-detectable cytochromes a + a3) could be quantitatively sedimented by low-speed centrifugation. In contrast to previous findings with Saccharomyces carlsbergensis, cytochrome c oxidase and another mitochondrial enzyme, succinate dehydrogenase, were completely sedimentable by zonal centrifugation in sucrose gradients in the presence of either 2 mM-MgCl2 or 0-4 mM-EDTA. Mitochondria were apparently smaller and of lower buoyant density in gradients containing EDTA. The bulk of the total units of malate dehydrogenase and NADH; cytochrome c oxidoreductase sedimented with mitochondria, whereas NADPH: cytochrome c oxidoreductase was located in fractions containing no mitochondria. The distributions of mitochondrial enzymes were heterogeneous in populations of mitochondria separated on the basis of size or density. The possible origins of mitochondrial heterogeneity in extracts of S. pombe are discussed with special reference to changes in the enzyme activities of cells during the cell cycle."} {"id": "PMID:180236", "title": "Biochemical and genetic characterization of a carbamyl phosphate synthetase mutant of Escherichia coli K12.", "content": "An unusual Escherichia coli K12 mutant for carbamyl phosphate synthetase is described. The mutation was generated by bacteriophage MUI insertion and left a 5% residual activity of the enzyme using either ammonia or glutamine as donors. The mutation is recessive to the wild-type allele and maps at or near the pyrA gene, but the mutant requires only arginine and not uracil for growth. By a second block in the pyrB gene it was possible to shift the accumulated carbamyl phosphate to arginine biosynthesis. The Km values and the levels of ornithine activation and inhibition by UMP were normal in the mutant enzyme.", "contents": "Biochemical and genetic characterization of a carbamyl phosphate synthetase mutant of Escherichia coli K12. An unusual Escherichia coli K12 mutant for carbamyl phosphate synthetase is described. The mutation was generated by bacteriophage MUI insertion and left a 5% residual activity of the enzyme using either ammonia or glutamine as donors. The mutation is recessive to the wild-type allele and maps at or near the pyrA gene, but the mutant requires only arginine and not uracil for growth. By a second block in the pyrB gene it was possible to shift the accumulated carbamyl phosphate to arginine biosynthesis. The Km values and the levels of ornithine activation and inhibition by UMP were normal in the mutant enzyme."} {"id": "PMID:180237", "title": "Stability of enzymes in starving Arthrobacter crystallopoietes.", "content": "Cell-free extracts prepared from spherical and rod-shaped cells of Arthrobacter crystallopoietes were assayed for enzymes during various periods of starvation. The level of NADH oxidase dropped to 20 and 30%, respectively, in spherical and rod-shaped cells during the first 1 to 2 days of starvation and then remained constant for 9 days. Catalase activity decreased continuously and reached a low level in 9 days. Enzymes involved in glucose metabolism and the tricarboxylic acid cycle were stable for the duration of the experiment (about 1 week). Succinic dehydrogenase, fumarase and aconitase were stable during 21 days of starvation, which is the longest time enzymes have been shown to be stable in any bacterium under conditions of total starvation.", "contents": "Stability of enzymes in starving Arthrobacter crystallopoietes. Cell-free extracts prepared from spherical and rod-shaped cells of Arthrobacter crystallopoietes were assayed for enzymes during various periods of starvation. The level of NADH oxidase dropped to 20 and 30%, respectively, in spherical and rod-shaped cells during the first 1 to 2 days of starvation and then remained constant for 9 days. Catalase activity decreased continuously and reached a low level in 9 days. Enzymes involved in glucose metabolism and the tricarboxylic acid cycle were stable for the duration of the experiment (about 1 week). Succinic dehydrogenase, fumarase and aconitase were stable during 21 days of starvation, which is the longest time enzymes have been shown to be stable in any bacterium under conditions of total starvation."} {"id": "PMID:180238", "title": "Classification of micrococci on the basis of deoxyribonucleic acid homology.", "content": "The DNA homology relationships of 25 micrococci (15 strains of Micrococcus, eight strains of Sarcina and two strains of Staphylococcus) were studied by the deoxyribonucleic acid hybridization method using nuclease S1, an endonuclease specific for single-stranded DNA molecules. Nineteen of the strains were classified into three groups. Group I contained Micrococcus lysodeikticus IAMI056, M. luteus IAMI1010, M. flavus IAMI2005 and IAMI2006, Sarcina flava IAMI2007 and IAMI1006. S. subflava IAMI2009, S. lutea ATCC381, and ATCC382, and M. luteus IAMI1006. Group II contained M. roseus IAMI315, ATCC412, ATCC185 and IAMI295. Group III contained S. lutea IAMI099, IFO3232 and ATCC383, M. varians ATCC399 and Staphylococcus lactis ATCC15306. Micrococcus luteus IAMI097, M. varians ATCC19099 and ATCC19100, M. conglomeratus IAMI459 and IAMI470, and St. aureus IAMI011 could not be assigned to any of the three groups. The grouping corresponds to that derived from the results of differential lysis by lysozyme, 'lytic enzyme 2' from Cytophaga sp., or Streptomyces albus G enzyme; and to types of peptidoglycan in the cell walls and genetic transformation. The usefulness of classification based on sensitivity to various lytic enzymes was demonstrated. Group I probably coincides with M. luteus of Bergey's Manual of Determinative Bacteriology (1974), and groups II and III with M. roseus and M. varians respectively.", "contents": "Classification of micrococci on the basis of deoxyribonucleic acid homology. The DNA homology relationships of 25 micrococci (15 strains of Micrococcus, eight strains of Sarcina and two strains of Staphylococcus) were studied by the deoxyribonucleic acid hybridization method using nuclease S1, an endonuclease specific for single-stranded DNA molecules. Nineteen of the strains were classified into three groups. Group I contained Micrococcus lysodeikticus IAMI056, M. luteus IAMI1010, M. flavus IAMI2005 and IAMI2006, Sarcina flava IAMI2007 and IAMI1006. S. subflava IAMI2009, S. lutea ATCC381, and ATCC382, and M. luteus IAMI1006. Group II contained M. roseus IAMI315, ATCC412, ATCC185 and IAMI295. Group III contained S. lutea IAMI099, IFO3232 and ATCC383, M. varians ATCC399 and Staphylococcus lactis ATCC15306. Micrococcus luteus IAMI097, M. varians ATCC19099 and ATCC19100, M. conglomeratus IAMI459 and IAMI470, and St. aureus IAMI011 could not be assigned to any of the three groups. The grouping corresponds to that derived from the results of differential lysis by lysozyme, 'lytic enzyme 2' from Cytophaga sp., or Streptomyces albus G enzyme; and to types of peptidoglycan in the cell walls and genetic transformation. The usefulness of classification based on sensitivity to various lytic enzymes was demonstrated. Group I probably coincides with M. luteus of Bergey's Manual of Determinative Bacteriology (1974), and groups II and III with M. roseus and M. varians respectively."} {"id": "PMID:180239", "title": "Permissiveness of mouse, monkey and hybrid cells to encephalomyocarditis (EMC) virus.", "content": "Encephalomyocarditis (EMC) virus replicates to high titre in permissive mouse kidney (MKS) cells but poorly in monkey kidney (CV1) cells. The permissiveness of monkey-mouse hybrid cells varies according to their chromosomal content. In monkey cells, the synthesis of both single-stranded and double-stranded virus RNA is restricted; in semi-permissive hybrid clones, the double-stranded RNA is synthesized normally, whereas the synthesis of the single-stranded RNA is inhibited. Thus, it seems that more than one restrictive event is responsible for the low permissiveness of monkey cells to EMC virus.", "contents": "Permissiveness of mouse, monkey and hybrid cells to encephalomyocarditis (EMC) virus. Encephalomyocarditis (EMC) virus replicates to high titre in permissive mouse kidney (MKS) cells but poorly in monkey kidney (CV1) cells. The permissiveness of monkey-mouse hybrid cells varies according to their chromosomal content. In monkey cells, the synthesis of both single-stranded and double-stranded virus RNA is restricted; in semi-permissive hybrid clones, the double-stranded RNA is synthesized normally, whereas the synthesis of the single-stranded RNA is inhibited. Thus, it seems that more than one restrictive event is responsible for the low permissiveness of monkey cells to EMC virus."} {"id": "PMID:180240", "title": "Enhancement of polysome formation and protein synthesis in Sendai virus-infected cells.", "content": "A considerable stimulation of total protein synthesis in Sendai virus-infected chicken fibroblasts occurred 18 h after infection. The stimulation of synthesis was shown to be due mainly to the synthesis of virus-specific proteins; the synthesis of host proteins was either unchanged or slightly enhanced. The level of functional polyribosomes in virus-infected cells was also increased as compared to that in mock-infected control while the number of free 80S ribosomes was proportionally decreased.", "contents": "Enhancement of polysome formation and protein synthesis in Sendai virus-infected cells. A considerable stimulation of total protein synthesis in Sendai virus-infected chicken fibroblasts occurred 18 h after infection. The stimulation of synthesis was shown to be due mainly to the synthesis of virus-specific proteins; the synthesis of host proteins was either unchanged or slightly enhanced. The level of functional polyribosomes in virus-infected cells was also increased as compared to that in mock-infected control while the number of free 80S ribosomes was proportionally decreased."} {"id": "PMID:180241", "title": "Ribonucleotides in infectious bovine rhinotracheitis virus DNA.", "content": "Infectious bovine rhinotracheitis (IBR) virus was grown in the presence of 5-3H-uridine in a continuous line of bovine kidney cells. 5-3H-uridine was found to be associated with viral nucleocapsids. Furthermore, purification of the viral nucleic acid present in nucleocapsids illustrated that 5-3H-uridine was part of the viral nucleic acid. Purification of viral DNA from infected cells also indicated that 5-3H-uridine was associated with viral nucleic acid possibly as ribonucleotides. The label was identified as RNA by measuring its susceptibility to RNase and analysis of the bases. Short pulses with 5-3H-uridine, resulted in labelled nucleic acid which was extremely sensitive to RNase and alkali but resistant to DNase. Nucleotide analysis indicated that after short pulses all the radioactivity was associated with the base uracil whereas upon longer labelling periods a large percentage of the label was associated with cytosine. However even if viral DNA was isolated from nucleocapsids there was still some radioactivity associated with uracil. Sedimentation of heat denatured 5-3H-uridine label viral nucleic acid in CS2SO4 indicated that the label sedimented at a density of single stranded DNA suggesting that the ribonucleotides are covalently linked to the viral DNA.", "contents": "Ribonucleotides in infectious bovine rhinotracheitis virus DNA. Infectious bovine rhinotracheitis (IBR) virus was grown in the presence of 5-3H-uridine in a continuous line of bovine kidney cells. 5-3H-uridine was found to be associated with viral nucleocapsids. Furthermore, purification of the viral nucleic acid present in nucleocapsids illustrated that 5-3H-uridine was part of the viral nucleic acid. Purification of viral DNA from infected cells also indicated that 5-3H-uridine was associated with viral nucleic acid possibly as ribonucleotides. The label was identified as RNA by measuring its susceptibility to RNase and analysis of the bases. Short pulses with 5-3H-uridine, resulted in labelled nucleic acid which was extremely sensitive to RNase and alkali but resistant to DNase. Nucleotide analysis indicated that after short pulses all the radioactivity was associated with the base uracil whereas upon longer labelling periods a large percentage of the label was associated with cytosine. However even if viral DNA was isolated from nucleocapsids there was still some radioactivity associated with uracil. Sedimentation of heat denatured 5-3H-uridine label viral nucleic acid in CS2SO4 indicated that the label sedimented at a density of single stranded DNA suggesting that the ribonucleotides are covalently linked to the viral DNA."} {"id": "PMID:180242", "title": "Rescue of a rat tropic rat hepatoma virus pseudotype Kirsten sarcoma virus by co-cultivation of hepatoma tissue culture cells with K-NRK cells.", "content": "A rat tropic rat hepatoma virus pseudotype Kirsten sarcoma virus has been rescued from a co-culture of rat hepatoma tissue culture cells, HTC-HI, with Kirsten murine sarcoma transformed non-producer rat kidney cells (K-NRK). The virus complex, RHHV-KiMSV, released from the co-culture exhibited cell transformation ability on normal rat kidney (NRK) cells and showed a restricted host range limited to rat embryo fibroblasts and other normal rat cell lines. Evidence derived from indirect immunofluorescence assays demonstrated the association of rat helper virus specific gs-I and gs-3 antigens with RHHV-KiMSV transformed cells. RHHVKiMSV is currently being cultured at a titre as high as 10(4) f.f.u./ml in tissue culture, and thus offering opportunity for biochemical studies of rat viruses.", "contents": "Rescue of a rat tropic rat hepatoma virus pseudotype Kirsten sarcoma virus by co-cultivation of hepatoma tissue culture cells with K-NRK cells. A rat tropic rat hepatoma virus pseudotype Kirsten sarcoma virus has been rescued from a co-culture of rat hepatoma tissue culture cells, HTC-HI, with Kirsten murine sarcoma transformed non-producer rat kidney cells (K-NRK). The virus complex, RHHV-KiMSV, released from the co-culture exhibited cell transformation ability on normal rat kidney (NRK) cells and showed a restricted host range limited to rat embryo fibroblasts and other normal rat cell lines. Evidence derived from indirect immunofluorescence assays demonstrated the association of rat helper virus specific gs-I and gs-3 antigens with RHHV-KiMSV transformed cells. RHHVKiMSV is currently being cultured at a titre as high as 10(4) f.f.u./ml in tissue culture, and thus offering opportunity for biochemical studies of rat viruses."} {"id": "PMID:180243", "title": "Characterization of two particle types of calf rotavirus.", "content": "Two distinct types of rotavirus particle were isolated in caesium chloride density gradients. The higher density particle banded at 1-38 g/ml and measured 55 +/- 0-4 nm in diameter while the less dense particle banded at 1-36 g/ml, measured 66 +/- 0-4 nm in diameter and appeared to possess an extra outer capsid layer. Some forms intermediate between the two types were seen. Since the two particles had a similar but not identical morphology and polypeptide composition, they were considered to be different forms of the same virus. Infectivity was associated with the larger particle which contained one more polypeptide than the smaller particle.", "contents": "Characterization of two particle types of calf rotavirus. Two distinct types of rotavirus particle were isolated in caesium chloride density gradients. The higher density particle banded at 1-38 g/ml and measured 55 +/- 0-4 nm in diameter while the less dense particle banded at 1-36 g/ml, measured 66 +/- 0-4 nm in diameter and appeared to possess an extra outer capsid layer. Some forms intermediate between the two types were seen. Since the two particles had a similar but not identical morphology and polypeptide composition, they were considered to be different forms of the same virus. Infectivity was associated with the larger particle which contained one more polypeptide than the smaller particle."} {"id": "PMID:180244", "title": "Human fibroblast and leukocyte interferons show different dose-response curves in assay of cell protection.", "content": "Preparations of human fibroblast and leukocyte interferons of similar potency show markedly different dose-response curves in an assay which measures the degree of protection of tissue cultures against virus c.p.e. The effect is observed with both vesicular stomatitis virus (VSV) and Mengovirus, and is not altered by purification of the interferons.", "contents": "Human fibroblast and leukocyte interferons show different dose-response curves in assay of cell protection. Preparations of human fibroblast and leukocyte interferons of similar potency show markedly different dose-response curves in an assay which measures the degree of protection of tissue cultures against virus c.p.e. The effect is observed with both vesicular stomatitis virus (VSV) and Mengovirus, and is not altered by purification of the interferons."} {"id": "PMID:180245", "title": "Requirement of an adenylic acid-rich segment for the infectivity of encephalomyocarditis virus RNA.", "content": "About 80% of the RNA molecules extracted from encephalomyocarditis (EMC) virus were bound by oligo(dT)-cellulose under conditions which bind poly(A) but not poly(C) nor ribosomal RNA. This shows that most EMC virus RNA molecules contain a poly(A) tract. Both bound and unbound fractions contained RNA molecules of apparently the same size when examined by sucrose gradient sedimentation, but the bound fraction contained an adenylic acid-rich segment of about 20 nucleotides long, whereas the unbound RNA did not. The bound RNA had 200 times the specific infectivity of the unbound RNA which suggests that the poly(A) tract present in EMC virus RNA is required for infectivity.", "contents": "Requirement of an adenylic acid-rich segment for the infectivity of encephalomyocarditis virus RNA. About 80% of the RNA molecules extracted from encephalomyocarditis (EMC) virus were bound by oligo(dT)-cellulose under conditions which bind poly(A) but not poly(C) nor ribosomal RNA. This shows that most EMC virus RNA molecules contain a poly(A) tract. Both bound and unbound fractions contained RNA molecules of apparently the same size when examined by sucrose gradient sedimentation, but the bound fraction contained an adenylic acid-rich segment of about 20 nucleotides long, whereas the unbound RNA did not. The bound RNA had 200 times the specific infectivity of the unbound RNA which suggests that the poly(A) tract present in EMC virus RNA is required for infectivity."} {"id": "PMID:180246", "title": "Herpes simplex virus specified deoxypyrimidine kinase and the uptake of exogenous nucleosides by infected cells.", "content": "Herpes simplex virus can confer to thymidine kinaseless cells the ability to incorporate exogenously supplied thymidine into acid precipitable material. However no incorporation of exogenously supplied deoxycytidine into acid precipitable material can be detected after infection of deoxycytidine kinaseless cells by herpes simplex virus. This failure to incorporate exogenous deoxycytidine is not due to the failure of the deoxycytidine phosphorylating activity of the virus induced deoxycytidine kinase but to a block in the metabolism of deoxycytidine monophosphate in herpes simplex virus infected cells. This block becomes evident with the appearance of the virus induced deoxypyrimidine kinase activity.", "contents": "Herpes simplex virus specified deoxypyrimidine kinase and the uptake of exogenous nucleosides by infected cells. Herpes simplex virus can confer to thymidine kinaseless cells the ability to incorporate exogenously supplied thymidine into acid precipitable material. However no incorporation of exogenously supplied deoxycytidine into acid precipitable material can be detected after infection of deoxycytidine kinaseless cells by herpes simplex virus. This failure to incorporate exogenous deoxycytidine is not due to the failure of the deoxycytidine phosphorylating activity of the virus induced deoxycytidine kinase but to a block in the metabolism of deoxycytidine monophosphate in herpes simplex virus infected cells. This block becomes evident with the appearance of the virus induced deoxypyrimidine kinase activity."} {"id": "PMID:180247", "title": "The cleavage of polyoma virus DNA by restriction enzymes KpnI and PstI.", "content": "The action of two restriction endonucleases on polyoma virus DNA has been examined and the sites at which they cleave the DNA located. One of the enzymes, KpnI from Klebsiella pneumoniae OK8, cleaves polyoma DNA twice at about 11-6 and 59-2% from the EcoRI site. The other enzyme, PstI from Providencia stuartii 164, cleaves polyoma DNA five times at about 14-8, 16-5, 32-6, 50-3 and 80-0% from the EcoRI site. Some of the cleavages produced by these enzymes alone, or in conjunction with other endonucleases, may be of use in the isolation of regions of particular interest from the virus DNA.", "contents": "The cleavage of polyoma virus DNA by restriction enzymes KpnI and PstI. The action of two restriction endonucleases on polyoma virus DNA has been examined and the sites at which they cleave the DNA located. One of the enzymes, KpnI from Klebsiella pneumoniae OK8, cleaves polyoma DNA twice at about 11-6 and 59-2% from the EcoRI site. The other enzyme, PstI from Providencia stuartii 164, cleaves polyoma DNA five times at about 14-8, 16-5, 32-6, 50-3 and 80-0% from the EcoRI site. Some of the cleavages produced by these enzymes alone, or in conjunction with other endonucleases, may be of use in the isolation of regions of particular interest from the virus DNA."} {"id": "PMID:180248", "title": "Use of a transfection method to demonstrate a monolayer cell transforming agent from the EB3 line of Burkitt's lymphoma cells.", "content": "Primary human amnion cell monolayers which had been treated with DEAE-dextran, washed, and then inoculated with sonicated cells of the EB3 line of Burkitt's lymphoma cells developed foci of transformed amnion cells 7 to 14 days later. When either the DEAE-dextran or the sonicate was omitted, no significant transformation was found. The foci consisted of enlarging mounds of rapidly dividing cells, which upon subculturing continued their high miotic activity; and strains or lines of the transformed amnion cells were thus readily established. The modal number of chromosomes in such lines was 65 instead of the normal 46. Not all human amnions yielded cells transformable by EB3 cell sonicate, as determined by direct comparisions using the same cultural conditions and testing with the same fresh sonicate preparation in the same experiment. Overall, it appeared that only about 40 to 50% of the amnions yielded transformable cell monolayers; the rest gave monolayers apprently completely refractory to the transformation. The transformed amnion cells contained nuclear and cytoplasmic Epstein-Barr virus (EBV) antigen(s), as revealed by indirect immunofluorescence tests. EB3 cell sonicate also caused the appearance of rapidly growing transformed cell foci on secondary rat embryo cell monolayers which had been sensitized with DEAE-dextran. Calcium in the cell maintenance medium decreased the number of transformed foci found, both on the human and on the rat cell monlayers. Sonicates of cultured normal human leucocytes had no such transforming activity for either the human or the rat cells. The transforming agent in EB3 cell sonicate was completely destructible by either deoxyribonuclease or trypsin, but not by ribonuclease, and was not neutralizable by anti-EBV serum. The simplest interpretation of these results is that the transforming agent is part of all of the EBV DNA plus some necessary protein, with both the DNA and the protein accessible to hydrolytic enzyme action.", "contents": "Use of a transfection method to demonstrate a monolayer cell transforming agent from the EB3 line of Burkitt's lymphoma cells. Primary human amnion cell monolayers which had been treated with DEAE-dextran, washed, and then inoculated with sonicated cells of the EB3 line of Burkitt's lymphoma cells developed foci of transformed amnion cells 7 to 14 days later. When either the DEAE-dextran or the sonicate was omitted, no significant transformation was found. The foci consisted of enlarging mounds of rapidly dividing cells, which upon subculturing continued their high miotic activity; and strains or lines of the transformed amnion cells were thus readily established. The modal number of chromosomes in such lines was 65 instead of the normal 46. Not all human amnions yielded cells transformable by EB3 cell sonicate, as determined by direct comparisions using the same cultural conditions and testing with the same fresh sonicate preparation in the same experiment. Overall, it appeared that only about 40 to 50% of the amnions yielded transformable cell monolayers; the rest gave monolayers apprently completely refractory to the transformation. The transformed amnion cells contained nuclear and cytoplasmic Epstein-Barr virus (EBV) antigen(s), as revealed by indirect immunofluorescence tests. EB3 cell sonicate also caused the appearance of rapidly growing transformed cell foci on secondary rat embryo cell monolayers which had been sensitized with DEAE-dextran. Calcium in the cell maintenance medium decreased the number of transformed foci found, both on the human and on the rat cell monlayers. Sonicates of cultured normal human leucocytes had no such transforming activity for either the human or the rat cells. The transforming agent in EB3 cell sonicate was completely destructible by either deoxyribonuclease or trypsin, but not by ribonuclease, and was not neutralizable by anti-EBV serum. The simplest interpretation of these results is that the transforming agent is part of all of the EBV DNA plus some necessary protein, with both the DNA and the protein accessible to hydrolytic enzyme action."} {"id": "PMID:180249", "title": "Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature-sensitive mutants of HSV strain 17.", "content": "The polypeptides induced in cells infected with a Glasgow isolate of HSV-I (17 syn+) have been characterized by SDS polyacrylamide gel electrophoresis. Study of the kinetics of synthesis in three cell lines has detected a total of 52 polypeptides, 33 of which can be identified in polypeptide profiles of purified virions. These include six low mol. wt. polypeptides that have not been previously reported. Several polypeptides were labelled with glucosamine in infected BHK cells. The different polypeptide patterns obtained at permissive (31 degrees C) and nonpermissive (38 degrees C) temperature in cells infected with 16 temperature-sensitive (ts) mutants are reported. The effect of multiplicity of infection (m.o.i.) on the polypeptide profile has been examined for two of the DNA -ve mutants: below ten, the profile varied with the m.o.i. whereas above ten it was constant. All mutants were therefore examined at an m.o.i. of approx. 20. Mutants from the same complementation group showed very similar profiles. A number of general conclusions concerning control of protein synthesis in HSV infected cells can be made: (I) As most of the 16 ts mutants affected the synthesis of several or many polypeptides it follows that a large proportion of genome specifies controlling functions. (2) The high frequency with which some polypeptides were affected suggests they are at or near the terminus of biosynthetic pathways which are under multiple control. (3) Conversely, some polypeptides were affected with a low frequency suggesting that their synthesis is not dependent on the expression of many virus functions. (4) Several individual ts mutations lead to the synthesis of increased amounts of different large polypeptides. (5) Analysis of every band detectably affected by at least one ts mutation has disclosed nine classes of dependence relationship between polypeptide synthesis and the DNA phenotype of the mutants, illustrating that this relationship is complex and different for different polypeptides. (6) The inhibition of host protein synthesis by the virus may not be a simple single step process.", "contents": "Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature-sensitive mutants of HSV strain 17. The polypeptides induced in cells infected with a Glasgow isolate of HSV-I (17 syn+) have been characterized by SDS polyacrylamide gel electrophoresis. Study of the kinetics of synthesis in three cell lines has detected a total of 52 polypeptides, 33 of which can be identified in polypeptide profiles of purified virions. These include six low mol. wt. polypeptides that have not been previously reported. Several polypeptides were labelled with glucosamine in infected BHK cells. The different polypeptide patterns obtained at permissive (31 degrees C) and nonpermissive (38 degrees C) temperature in cells infected with 16 temperature-sensitive (ts) mutants are reported. The effect of multiplicity of infection (m.o.i.) on the polypeptide profile has been examined for two of the DNA -ve mutants: below ten, the profile varied with the m.o.i. whereas above ten it was constant. All mutants were therefore examined at an m.o.i. of approx. 20. Mutants from the same complementation group showed very similar profiles. A number of general conclusions concerning control of protein synthesis in HSV infected cells can be made: (I) As most of the 16 ts mutants affected the synthesis of several or many polypeptides it follows that a large proportion of genome specifies controlling functions. (2) The high frequency with which some polypeptides were affected suggests they are at or near the terminus of biosynthetic pathways which are under multiple control. (3) Conversely, some polypeptides were affected with a low frequency suggesting that their synthesis is not dependent on the expression of many virus functions. (4) Several individual ts mutations lead to the synthesis of increased amounts of different large polypeptides. (5) Analysis of every band detectably affected by at least one ts mutation has disclosed nine classes of dependence relationship between polypeptide synthesis and the DNA phenotype of the mutants, illustrating that this relationship is complex and different for different polypeptides. (6) The inhibition of host protein synthesis by the virus may not be a simple single step process."} {"id": "PMID:180250", "title": "Inhibition of murine sarcoma virus induced transformation by adenovirus structural proteins.", "content": "The purified fibre and hexon of adenovirus 12 inhibit the transformation in tissue culture of murine sarcoma virus (msv-m) by as much as 80% and 70%, respectively, when they are added to cells 8 to 2o h before MSV-M infection. During a 12 h period, only about 6 to 8% of added radiolabelled viral proteins become associated with cells (or I-O mug protein bound/10(5) cells). No inhibition occurs when the proteins are added simultaneously with MSV-M or 90 min or 4 h after MSV-M. There is also a direct correlation between the extent of focus inhibition and the concentrations of viral proteins used. Concentrations of viral proteins used to inhibit cell transformation do not affect cell growth, but do reduce cell macromolecular synthesis.", "contents": "Inhibition of murine sarcoma virus induced transformation by adenovirus structural proteins. The purified fibre and hexon of adenovirus 12 inhibit the transformation in tissue culture of murine sarcoma virus (msv-m) by as much as 80% and 70%, respectively, when they are added to cells 8 to 2o h before MSV-M infection. During a 12 h period, only about 6 to 8% of added radiolabelled viral proteins become associated with cells (or I-O mug protein bound/10(5) cells). No inhibition occurs when the proteins are added simultaneously with MSV-M or 90 min or 4 h after MSV-M. There is also a direct correlation between the extent of focus inhibition and the concentrations of viral proteins used. Concentrations of viral proteins used to inhibit cell transformation do not affect cell growth, but do reduce cell macromolecular synthesis."} {"id": "PMID:180251", "title": "Demonstration of a core in poliovirus particles by electron microscopy.", "content": "Electron microscopic examination of poliovirus in CsCl-solutions without conventional staining with phosphotungstic acid or uranyl acetate revealed the existence of cores inside poliovirus particles. Empty capsids could not be visualized by this technique. Evidently, CsCl can enhance the contrast of the virus particle to an extent sufficient for the study of poliovirus particles by electron microscopy under conditions in which they exhibit specific properties.", "contents": "Demonstration of a core in poliovirus particles by electron microscopy. Electron microscopic examination of poliovirus in CsCl-solutions without conventional staining with phosphotungstic acid or uranyl acetate revealed the existence of cores inside poliovirus particles. Empty capsids could not be visualized by this technique. Evidently, CsCl can enhance the contrast of the virus particle to an extent sufficient for the study of poliovirus particles by electron microscopy under conditions in which they exhibit specific properties."} {"id": "PMID:180255", "title": "Some electrical properties of motor units and their effects on the methods of estimating motor unit numbers.", "content": "Long train (50) electrical pulses were applied to the ulnar, median, and deep peroneal nerves. The probability of firing, or firing index, of the first motor units (MU) recorded by surface and needle electrodes in the first dorsal interosseous, thenar, and extensor digitorum brevis muscles varied from 0-100% as the stimulus was increased from a minimum threshold voltage (V) to V + delta V (delta V = 2-4 volts). The voltage interval, delta V (firing level range), of even the first few MU recruited greatly overlapped in normal subjects, but may overlap less in some neuromuscular disorders such as amyotrophic lateral sclerosis. The mean size of the single MU isolated by (1) isometric voluntary contraction method, (2) F recurrent discharge method, and (3) stimulation at multiple locations along the nerve, were more than twice as large as the mean size of the incremental steps evoked by graded electrical stimulation. These results suggest that methods of estimating the number of MU in a muscle should incorporate a correction for the fluctuations in excitability and overlap in firing levels of MU, and in addition should include larger MU in the estimation of the mean MU potential.", "contents": "Some electrical properties of motor units and their effects on the methods of estimating motor unit numbers. Long train (50) electrical pulses were applied to the ulnar, median, and deep peroneal nerves. The probability of firing, or firing index, of the first motor units (MU) recorded by surface and needle electrodes in the first dorsal interosseous, thenar, and extensor digitorum brevis muscles varied from 0-100% as the stimulus was increased from a minimum threshold voltage (V) to V + delta V (delta V = 2-4 volts). The voltage interval, delta V (firing level range), of even the first few MU recruited greatly overlapped in normal subjects, but may overlap less in some neuromuscular disorders such as amyotrophic lateral sclerosis. The mean size of the single MU isolated by (1) isometric voluntary contraction method, (2) F recurrent discharge method, and (3) stimulation at multiple locations along the nerve, were more than twice as large as the mean size of the incremental steps evoked by graded electrical stimulation. These results suggest that methods of estimating the number of MU in a muscle should incorporate a correction for the fluctuations in excitability and overlap in firing levels of MU, and in addition should include larger MU in the estimation of the mean MU potential."} {"id": "PMID:180256", "title": "Sensory and motor residual latency measurements in helathy patients and patients with neuropathy-part 1.", "content": "Median and ulnar nerves were evaluated using established nerve conduction techniques in a control population and in a population of patients with neuropathy. Motor and sensory residual latencies were obtained. The main contributor to the latencies was slowing of the nerve conduction in the smaller attenuated nerve fibres of the hand and fingers.", "contents": "Sensory and motor residual latency measurements in helathy patients and patients with neuropathy-part 1. Median and ulnar nerves were evaluated using established nerve conduction techniques in a control population and in a population of patients with neuropathy. Motor and sensory residual latencies were obtained. The main contributor to the latencies was slowing of the nerve conduction in the smaller attenuated nerve fibres of the hand and fingers."} {"id": "PMID:180257", "title": "Neurological disorders in the elderly at home.", "content": "Eight hundred and eight subjects participated in three surveys of random samples of people aged 65 years or more living in their own homes. Neurological history and examination showed the prevalence of completed stroke to be 73 per 1000. Eighty-seven subjects per 1000 gave a history of transient cerebral ischaemic attacks. These prevalence rates were unaffected by age or sex. Senile dementia was diagnosed in 24 subjects per 1000 under 75 years and 109 per 1000 over that age. The prevalence of dementia of all types was 43 per 1000 under, and 140 per 1000, over 75 years of age. Parkinsonism was diagnosed in 16 subjects per 1000, and essential tremor in 17 per 1000. The prevalence of epilepsy was four subject per 1000. Other neurological disorders were diagnosed in 36 subjects, and a similar number had neurological abnormalities to which a definite diagnosis could not be given.", "contents": "Neurological disorders in the elderly at home. Eight hundred and eight subjects participated in three surveys of random samples of people aged 65 years or more living in their own homes. Neurological history and examination showed the prevalence of completed stroke to be 73 per 1000. Eighty-seven subjects per 1000 gave a history of transient cerebral ischaemic attacks. These prevalence rates were unaffected by age or sex. Senile dementia was diagnosed in 24 subjects per 1000 under 75 years and 109 per 1000 over that age. The prevalence of dementia of all types was 43 per 1000 under, and 140 per 1000, over 75 years of age. Parkinsonism was diagnosed in 16 subjects per 1000, and essential tremor in 17 per 1000. The prevalence of epilepsy was four subject per 1000. Other neurological disorders were diagnosed in 36 subjects, and a similar number had neurological abnormalities to which a definite diagnosis could not be given."} {"id": "PMID:180258", "title": "Metronidazole neuropathy.", "content": "Two patients are described who developed sensory neuropathy after the ingestion of 30.6 and 114 g metronidazole respectively. The drug, widely used in gastroenterological and gynaecological practice, has not hitherto been considered neurotoxic. The implications are stressed in relation to the differential diagnosis of patients with gastroenterological disorders who develop peripheral neuropathy.", "contents": "Metronidazole neuropathy. Two patients are described who developed sensory neuropathy after the ingestion of 30.6 and 114 g metronidazole respectively. The drug, widely used in gastroenterological and gynaecological practice, has not hitherto been considered neurotoxic. The implications are stressed in relation to the differential diagnosis of patients with gastroenterological disorders who develop peripheral neuropathy."} {"id": "PMID:180259", "title": "Diencephalic amnesia: a reappraisal.", "content": "The anatomical basis of memory disorder related to lesions of the diencephalon is a controversial matter. A study of a patient who developed severe amnesia in association with bilateral metastatic tumour invasion of the medial and posterior thalamus is reported. The findings in this case have led to further discussion of this unsettled issue.", "contents": "Diencephalic amnesia: a reappraisal. The anatomical basis of memory disorder related to lesions of the diencephalon is a controversial matter. A study of a patient who developed severe amnesia in association with bilateral metastatic tumour invasion of the medial and posterior thalamus is reported. The findings in this case have led to further discussion of this unsettled issue."} {"id": "PMID:180260", "title": "Muscle wasting after prolonged hypoglycaemic coma: case report with electrophysiological data.", "content": "A case of distal muscle wasting associated with hypoglycaemia is described. Motor and sensory conduction studies are reported that provide little evidence of a hypoglycaemic peripheral neuropathy. Damage to anterior horn cells or motor roots appears to be a more likely explanation for the amyotrophy. Recovery occurred clinically with evidence of reinnervation by axonal collateral sprouting.", "contents": "Muscle wasting after prolonged hypoglycaemic coma: case report with electrophysiological data. A case of distal muscle wasting associated with hypoglycaemia is described. Motor and sensory conduction studies are reported that provide little evidence of a hypoglycaemic peripheral neuropathy. Damage to anterior horn cells or motor roots appears to be a more likely explanation for the amyotrophy. Recovery occurred clinically with evidence of reinnervation by axonal collateral sprouting."} {"id": "PMID:180261", "title": "Bulbocavernosus reflex in normal men and in patients with neurogenic bladder and/or impotence.", "content": "The bulbocavernosus reflex was investigated electrophysiologically in 14 normal adult male subjects and in 80 patients with neurogenic bladders and/or impotence due to various neurological causes as well as in patients with functional impotence. The glans penis was stimulated superficially by single electrical shocks and the reflex responses were recorded from the bulbocavernosus (BC) and the striated anal sphincter muscles by means of concentric needle EMG electrodes. In all normal subjects, the BC reflex was recorded from the BC muscle as a stable and constant response having a mean latency of 36.1 msec. A response from the external anal sphincter was obtained in only 21% of the subjects investigated. In 13 patients with cauda equina lesions, the BC reflex was either absent or was present with a prolonged latency. Twenty-two patients with polyneuropathy of various causes were also investigated; in these patients the latency of the BC reflex was significantly greater than in the normal controls, but the most abnormal results were obtained in cases of alcoholic polyneuropathy. In the 19 cases of spinal cord disease with spasticity the BC reflex response was very intense, often with after discharges but latency values were within normal limits. In the 16 cases with functional impotence, the BC reflexes were basically normal; but in 3 cases, the threshold of the reflex was significantly raised, and in 1 case a prolonged latency was observed. The value and the practical application of the BC reflex in the BC reflex in the differential diagnosis of bladder dysfunction and of impotence was stressed.", "contents": "Bulbocavernosus reflex in normal men and in patients with neurogenic bladder and/or impotence. The bulbocavernosus reflex was investigated electrophysiologically in 14 normal adult male subjects and in 80 patients with neurogenic bladders and/or impotence due to various neurological causes as well as in patients with functional impotence. The glans penis was stimulated superficially by single electrical shocks and the reflex responses were recorded from the bulbocavernosus (BC) and the striated anal sphincter muscles by means of concentric needle EMG electrodes. In all normal subjects, the BC reflex was recorded from the BC muscle as a stable and constant response having a mean latency of 36.1 msec. A response from the external anal sphincter was obtained in only 21% of the subjects investigated. In 13 patients with cauda equina lesions, the BC reflex was either absent or was present with a prolonged latency. Twenty-two patients with polyneuropathy of various causes were also investigated; in these patients the latency of the BC reflex was significantly greater than in the normal controls, but the most abnormal results were obtained in cases of alcoholic polyneuropathy. In the 19 cases of spinal cord disease with spasticity the BC reflex response was very intense, often with after discharges but latency values were within normal limits. In the 16 cases with functional impotence, the BC reflexes were basically normal; but in 3 cases, the threshold of the reflex was significantly raised, and in 1 case a prolonged latency was observed. The value and the practical application of the BC reflex in the BC reflex in the differential diagnosis of bladder dysfunction and of impotence was stressed."} {"id": "PMID:180262", "title": "Antibodies to Epstein-Barr virus in neurological diseases.", "content": "An association of evidence of Epstein-Barr virus (EBV) infection in 3 different cases of neurological disease not related to infectious monomucleosis is reported. A rise in antibody titres to EBV-viral capsid antigen (VCA) and early antigen (EA) in the serum and CSF was demonstrated in a patient with acute encephalitis and in a patient with a psychotic-like organic brain syndrome. Both patients demonstrated albuminocytological dissociation in the cerebrospinal fluid. IgM antibodies specific to EBV-VCA indicating a primary infection by EBV were found in both patients. In the second, concomitant infection with HSV1 probably preceding EBV infection was found. In the third patient with polyneuritis, elevated antibody titres to EBV-VCA were demonstrated. No evidence of penetration of antibodies to EBV through the blood-brain barrier, resulting from the elevated level in the serum, was demonstrated.", "contents": "Antibodies to Epstein-Barr virus in neurological diseases. An association of evidence of Epstein-Barr virus (EBV) infection in 3 different cases of neurological disease not related to infectious monomucleosis is reported. A rise in antibody titres to EBV-viral capsid antigen (VCA) and early antigen (EA) in the serum and CSF was demonstrated in a patient with acute encephalitis and in a patient with a psychotic-like organic brain syndrome. Both patients demonstrated albuminocytological dissociation in the cerebrospinal fluid. IgM antibodies specific to EBV-VCA indicating a primary infection by EBV were found in both patients. In the second, concomitant infection with HSV1 probably preceding EBV infection was found. In the third patient with polyneuritis, elevated antibody titres to EBV-VCA were demonstrated. No evidence of penetration of antibodies to EBV through the blood-brain barrier, resulting from the elevated level in the serum, was demonstrated."} {"id": "PMID:180263", "title": "In vivo reversal of thyroxine induction of DNA synthesis by dibutyrly cyclic AMP in developing rat cerebellum.", "content": "Thyroxine, dibutyryl cyclic AMP, and a combination of both drugs were administered daily from birth to 2, 2 and 3 pups, respectively from each of 5 litters of Sprague-Dawley rats. Body weight, brain weight, cerebellar weight, and cerebellar DNA were measured in each animal at age 5 days and compared with values from a pair of controls from each litter. Cerebellar weight and DNA content were affected more severely than body weight in cyclic AMP-treated animals, with cerebellar DNA reduced significantly to 88% of control values. Cerebellar DNA was significantly elevated to 117% of control values in thyroxine-treated animals. This augmentation of cerebellar DNA synthesis by thyroxine was negated by administration of dibutyryl cyclic AMP 10 min prior to the thyroxine injection. These results support an hypothesis that the enhancement of cerebellar cell division by thyroxine involves an increase in the ratio of intracellular cyclic guanosine monophosphate to cyclic adenosine monophosphate. The reversal of the thyroxine-induced increase in cerebellar DNA synthesis by a prior injection of dibutyryl cyclic AMP suggests that the early stimulation of cell division by thyroxine may be mediated by cyclic AMP, and that the intracellular balance between cerebellar cyclic AMP and cyclic GMP was distorted by in vivo elevation of intracellular cyclic AMP levels.", "contents": "In vivo reversal of thyroxine induction of DNA synthesis by dibutyrly cyclic AMP in developing rat cerebellum. Thyroxine, dibutyryl cyclic AMP, and a combination of both drugs were administered daily from birth to 2, 2 and 3 pups, respectively from each of 5 litters of Sprague-Dawley rats. Body weight, brain weight, cerebellar weight, and cerebellar DNA were measured in each animal at age 5 days and compared with values from a pair of controls from each litter. Cerebellar weight and DNA content were affected more severely than body weight in cyclic AMP-treated animals, with cerebellar DNA reduced significantly to 88% of control values. Cerebellar DNA was significantly elevated to 117% of control values in thyroxine-treated animals. This augmentation of cerebellar DNA synthesis by thyroxine was negated by administration of dibutyryl cyclic AMP 10 min prior to the thyroxine injection. These results support an hypothesis that the enhancement of cerebellar cell division by thyroxine involves an increase in the ratio of intracellular cyclic guanosine monophosphate to cyclic adenosine monophosphate. The reversal of the thyroxine-induced increase in cerebellar DNA synthesis by a prior injection of dibutyryl cyclic AMP suggests that the early stimulation of cell division by thyroxine may be mediated by cyclic AMP, and that the intracellular balance between cerebellar cyclic AMP and cyclic GMP was distorted by in vivo elevation of intracellular cyclic AMP levels."} {"id": "PMID:180264", "title": "Hereditary motor peripheral neuropathy predominantly affecting the arms.", "content": "A kinship is described in which there was slowly progressive wasting and weakness of the muscles of the upper and occasionally of the lower limbs. Some members had hyperreflexia. There were no sensory abnormalities. Electrophysiological study suggested the presence of motor peripheral polyneuropathy. The condition appeared to be inherited as an autosomal dominant. The disorder does not appear typical of any of the known hereditary polyneuropathies and it is possible that it may represent a unique hereditary, dominantly motor, polyneuropathy. The significance of the hyperreflexia is uncertain, but raises the possibility of minor central involvement as well as peripheral neuropathy.", "contents": "Hereditary motor peripheral neuropathy predominantly affecting the arms. A kinship is described in which there was slowly progressive wasting and weakness of the muscles of the upper and occasionally of the lower limbs. Some members had hyperreflexia. There were no sensory abnormalities. Electrophysiological study suggested the presence of motor peripheral polyneuropathy. The condition appeared to be inherited as an autosomal dominant. The disorder does not appear typical of any of the known hereditary polyneuropathies and it is possible that it may represent a unique hereditary, dominantly motor, polyneuropathy. The significance of the hyperreflexia is uncertain, but raises the possibility of minor central involvement as well as peripheral neuropathy."} {"id": "PMID:180265", "title": "Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.", "content": "An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.", "contents": "Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin. An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest."} {"id": "PMID:180266", "title": "Gian axonal neuropathy--a generalized disorder of cytoplasmic microfilament formation.", "content": "Light and electron microscopy of a sural nerve biopsy obtained from a patient with giant axonal neuropathy revealed the presence of numerous axonal spheroids which were composed chiefly of neurofilaments. Large discrete masses of cytoplasmic microfilaments were also observed in endoneurial fibroblasts, endothelial cells, Schwann cells, perineurial cells and cultured skin fibroblasts. Neuronal degeneration in giant axonal neuropathy appears to be part of a generalized disorder of cytoplasmic microfilament formation.", "contents": "Gian axonal neuropathy--a generalized disorder of cytoplasmic microfilament formation. Light and electron microscopy of a sural nerve biopsy obtained from a patient with giant axonal neuropathy revealed the presence of numerous axonal spheroids which were composed chiefly of neurofilaments. Large discrete masses of cytoplasmic microfilaments were also observed in endoneurial fibroblasts, endothelial cells, Schwann cells, perineurial cells and cultured skin fibroblasts. Neuronal degeneration in giant axonal neuropathy appears to be part of a generalized disorder of cytoplasmic microfilament formation."} {"id": "PMID:180267", "title": "Melanoma of the pituitary. Case report.", "content": "A case is described in which a pigmented tumor occupied the pituitary fossa with a large suprasellar extension. Its histological and ultrastructural appearances resembled those of a melanoma. The origin of the tumor is discussed with particular reference to Rathke's pouch.", "contents": "Melanoma of the pituitary. Case report. A case is described in which a pigmented tumor occupied the pituitary fossa with a large suprasellar extension. Its histological and ultrastructural appearances resembled those of a melanoma. The origin of the tumor is discussed with particular reference to Rathke's pouch."} {"id": "PMID:180268", "title": "Pathogenesis of aqueductal occlusion in congenital murine hydrocephalus.", "content": "In a study of congenital hydrocephalus in the murine mutant (hy-3/hy-3), the authors found that aqueductal stenosis develops during the progression of hydrocephalus. In Stage 1 hydrocephalus (ventricular dilation and open aqueduct), a block in the subarachnoid space over the cerebral convexities causes the lateral and third ventricles to enlarge. The ependyma becomes stretched and a collection of edematous fluid forms in the subependymal layer. In Stage 2 hydrocephalus (edema in white matter around lateral ventricles and compression of quadrigeminal plate), edema develops peripheral to ependyma in the aqueduct and compresses the lateral surfaces of the aqueductal wall to obstruct the lumen. While periaqueductal edema is spreading, the forces of the expanding midline structures and the cystic occiital horns alter the relationship of brain structures. There is no proliferation of glia, but, rather, a \"simple stenosis\" which results from a combination of ventricular dilation, cerebral edema, brain shift, brain-stem compression, and brain-stem edema. In this study, normal ependymal specializations were observed that indicate a more active functional role for aqueductal ependyma than previously recognized.", "contents": "Pathogenesis of aqueductal occlusion in congenital murine hydrocephalus. In a study of congenital hydrocephalus in the murine mutant (hy-3/hy-3), the authors found that aqueductal stenosis develops during the progression of hydrocephalus. In Stage 1 hydrocephalus (ventricular dilation and open aqueduct), a block in the subarachnoid space over the cerebral convexities causes the lateral and third ventricles to enlarge. The ependyma becomes stretched and a collection of edematous fluid forms in the subependymal layer. In Stage 2 hydrocephalus (edema in white matter around lateral ventricles and compression of quadrigeminal plate), edema develops peripheral to ependyma in the aqueduct and compresses the lateral surfaces of the aqueductal wall to obstruct the lumen. While periaqueductal edema is spreading, the forces of the expanding midline structures and the cystic occiital horns alter the relationship of brain structures. There is no proliferation of glia, but, rather, a \"simple stenosis\" which results from a combination of ventricular dilation, cerebral edema, brain shift, brain-stem compression, and brain-stem edema. In this study, normal ependymal specializations were observed that indicate a more active functional role for aqueductal ependyma than previously recognized."} {"id": "PMID:180269", "title": "Relationship between bone uptake of 99mTc-pyrophosphate and hydroxyproline in blood and urine.", "content": "In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism.", "contents": "Relationship between bone uptake of 99mTc-pyrophosphate and hydroxyproline in blood and urine. In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism."} {"id": "PMID:180270", "title": "Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection.", "content": "Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid (11C-ACPC) has been prepared in multimillicurie amounts. The conversion of H11CN to 11C-ACPC (t1/2 = 20.4 min) was accomplished by a rapid (20-min) two-step high-temperature modification of the B\u00fccherer-Strecker amino acid synthesis technique, which should be applicable at other accelerator installations. Purification was by ion exchange techniques. Animal studies have indicated that 11C-ACPC is a potential tumor-localizing agent for detecting cancer in humans by nuclear medicine scanning techniques.", "contents": "Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection. Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid (11C-ACPC) has been prepared in multimillicurie amounts. The conversion of H11CN to 11C-ACPC (t1/2 = 20.4 min) was accomplished by a rapid (20-min) two-step high-temperature modification of the B\u00fccherer-Strecker amino acid synthesis technique, which should be applicable at other accelerator installations. Purification was by ion exchange techniques. Animal studies have indicated that 11C-ACPC is a potential tumor-localizing agent for detecting cancer in humans by nuclear medicine scanning techniques."} {"id": "PMID:180273", "title": "Ventilation and sleep states in newborn infants.", "content": "Recent studies have shown that ventilation in the newborn period is affected by sleep state. We investigated various measures affecting ventilation using the single breath airway occlusion technique in ten healthy, full-term newborn infants. There was a significant increase in respiratory rate and in minute ventilation in rapid eye movement sleep compared to non-REM sleep, and there was no significant change in tidal volume between the two sleep states. The variability of ventilation was increased in REM sleep, and inspiratory pressure at one-tenth of a second following airway occlusion was significantly increased in REM sleep. Effective elastance was similar in both sleep states. Measures that reflect activity of the Hering-Breuer reflex were significantly increased in non-REM sleep as compared with REM sleep. These results document the interdependence of sleep state and respiratory control mechanisms in full-term infants.", "contents": "Ventilation and sleep states in newborn infants. Recent studies have shown that ventilation in the newborn period is affected by sleep state. We investigated various measures affecting ventilation using the single breath airway occlusion technique in ten healthy, full-term newborn infants. There was a significant increase in respiratory rate and in minute ventilation in rapid eye movement sleep compared to non-REM sleep, and there was no significant change in tidal volume between the two sleep states. The variability of ventilation was increased in REM sleep, and inspiratory pressure at one-tenth of a second following airway occlusion was significantly increased in REM sleep. Effective elastance was similar in both sleep states. Measures that reflect activity of the Hering-Breuer reflex were significantly increased in non-REM sleep as compared with REM sleep. These results document the interdependence of sleep state and respiratory control mechanisms in full-term infants."} {"id": "PMID:180274", "title": "Respiratory syncytial virus infections in infants: quantitation and duration of shedding.", "content": "Infants hospitalized with respiratory syncytial virus infection were studied to delineate the quantitative shedding patterns and duration of shedding of RSV. Nasal wash specimens collected daily from 19 infants contained a mean maximal titer of 4.34 log10 50% tissue culture infective doses per milliliter. On admission, the mean titer was 4.14 log10 TCID50, with no consistent decline until after Day 6. The mean duration of shedding for 23 patients until they were virus negative was 6.7 days with a range of 1 to 21 days. Quantities of RSV shed were significantly greater in infants less than one month of age and in infants with evidence of pulmonary consolidation on chest roentgenogram. Shedding extended for a significantly longer time in infants with lower respiratory tract disease than in those with clinical manifestations limited to the upper respiratory tract.", "contents": "Respiratory syncytial virus infections in infants: quantitation and duration of shedding. Infants hospitalized with respiratory syncytial virus infection were studied to delineate the quantitative shedding patterns and duration of shedding of RSV. Nasal wash specimens collected daily from 19 infants contained a mean maximal titer of 4.34 log10 50% tissue culture infective doses per milliliter. On admission, the mean titer was 4.14 log10 TCID50, with no consistent decline until after Day 6. The mean duration of shedding for 23 patients until they were virus negative was 6.7 days with a range of 1 to 21 days. Quantities of RSV shed were significantly greater in infants less than one month of age and in infants with evidence of pulmonary consolidation on chest roentgenogram. Shedding extended for a significantly longer time in infants with lower respiratory tract disease than in those with clinical manifestations limited to the upper respiratory tract."} {"id": "PMID:180275", "title": "Protracted pneumonitis in young infants associated with perinatally acquired cytomegaloviral infection.", "content": "Two infants developed a protracted pneumonitis with lower respiratory obstruction beginning at one month of age. Lung biopsy in one suggested a viral etiology which prompted an extensive investigation of each infant for specific etiology. Virologic, serologic, immunologic, and electronmicroscopic studies indicated that cytomegalovirus was a major causative factor. The infections were apparently acquired at birth from infected maternal genital tracts and have persisted for prolonged periods of time. Evidence for gross immunologic defect as a precipitating cause was lacking. These infants serve to emphasize the possible pathologic potential of CMV when acquired in early life even in the absence of iatrogenic immunosuppression.", "contents": "Protracted pneumonitis in young infants associated with perinatally acquired cytomegaloviral infection. Two infants developed a protracted pneumonitis with lower respiratory obstruction beginning at one month of age. Lung biopsy in one suggested a viral etiology which prompted an extensive investigation of each infant for specific etiology. Virologic, serologic, immunologic, and electronmicroscopic studies indicated that cytomegalovirus was a major causative factor. The infections were apparently acquired at birth from infected maternal genital tracts and have persisted for prolonged periods of time. Evidence for gross immunologic defect as a precipitating cause was lacking. These infants serve to emphasize the possible pathologic potential of CMV when acquired in early life even in the absence of iatrogenic immunosuppression."} {"id": "PMID:180276", "title": "Long-term hepatocellular effects of hycanthone and of two other anti-Schistosomal drugs in mice infected with Schistosoma mansoni.", "content": "In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine.", "contents": "Long-term hepatocellular effects of hycanthone and of two other anti-Schistosomal drugs in mice infected with Schistosoma mansoni. In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine."} {"id": "PMID:180277", "title": "A study of the effects of p-chloromercuribenzene sulfonic acid on acetylcholine-induced responses of molluscan neurons.", "content": "The effects of the organic mercurial p-chloromercuribenzene sulfonic acid (PCMBS) on the acetylcholine receptors of two types of neurons from the marine gastropod Anisodoris nobilis were studied. Cell types were distinguished by the ion-specific conductance change resulting from applied cholinergic agents: in certain cells a conductance increase to Cl resulted (Cl-neurons); in other cells a cation conductance increase resulted (D cells). Exposure of the Cl-neurons to 1 mM PCMBS at 4 degrees C had two distinct effects: 1) the sensitivity of the membrane conductance to microelectrophoretically applied carbamylcholine was blocked in a few minutes; and 2) the membrane conductance slowly increased with an inversion potential which was the same as that of the cholinergically induced response. d-Turbocurarine did not appreciably reduce this conductance increase. However, applying carbamylcholine during the exposure period to PCMBS reduced the PCMBS response. The cholinergic response of D cells was affected to a much lesser degree by PCMBS.", "contents": "A study of the effects of p-chloromercuribenzene sulfonic acid on acetylcholine-induced responses of molluscan neurons. The effects of the organic mercurial p-chloromercuribenzene sulfonic acid (PCMBS) on the acetylcholine receptors of two types of neurons from the marine gastropod Anisodoris nobilis were studied. Cell types were distinguished by the ion-specific conductance change resulting from applied cholinergic agents: in certain cells a conductance increase to Cl resulted (Cl-neurons); in other cells a cation conductance increase resulted (D cells). Exposure of the Cl-neurons to 1 mM PCMBS at 4 degrees C had two distinct effects: 1) the sensitivity of the membrane conductance to microelectrophoretically applied carbamylcholine was blocked in a few minutes; and 2) the membrane conductance slowly increased with an inversion potential which was the same as that of the cholinergically induced response. d-Turbocurarine did not appreciably reduce this conductance increase. However, applying carbamylcholine during the exposure period to PCMBS reduced the PCMBS response. The cholinergic response of D cells was affected to a much lesser degree by PCMBS."} {"id": "PMID:180278", "title": "Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat.", "content": "When tityustoxin (TsTX, 1.43 muM; mol. wt. 6995) was applied to the rat phrenic nerve-diaphragm muscle preparation, both the directly and indirectly elicited muscle contractions were transiently potentiated by about 30 and 60%, respectively, and the half-relaxation time was prolonged to more than 10 times the control. The onset of potentiation of muscle contraction was immediate and coincided closely with the prolongation of the directly elicited action potential and depolarization of the muscle membrane but preceded the presynaptic effect of the toxin. TsTX antagonized the neuromuscular blockade produced by low concentrations of d-tubocurarine (6.5 muM) but not by higher concentrations of d-tubocurarine (13 muM) or by alpha-bungarotoxin (5 mug/ml). Single shocks to the nerve of toxin-treated muscles evoked repetitive end-plate potentials which summated and triggered action potentials and muscle contractions 15 minutes after exposure. After 25 minutes, the frequency of spontaneous transmitter release transiently increased from 2 to 550 sec-1 but was never blocked and there was no blockade of the acetylcholine receptors of chronically denervated muscle. Both the increase in miniature end-plate potential frequency and postsynaptic depolarization induced by TsTX could be blocked by tetrodotoxin, and the effects on end-plate potentials and action potentials could be blocked by lowering the external sodium concentration. Removal of calcium and addition of ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 10 mM) to the bathing fluid blocked the presynaptic but not postsynaptic effects of TsTX at 23 degrees C; at 37 degrees C the presynaptic effects of TsTX in a calcium-free medium with EGTA were depressed but still present. Delayed rectification and membrane electrical characteristics were unaffected by TsTX. The results indicate that TsTX depolarizes the pre- and postsynaptic membranes by increasing sodium permeability. The postsynaptic site of action is most likely to be the sarcolemmal membrane where TsTX delays Na inactivation and thus prolongs the active phase of muscle contraction. Presynaptically, TsTX has two sites of action: 1) it depolarizes the nerve terminal thus facilitating the spontaneous release of transmitter; and 2) it acts at the membrane of the unmyelinated nerve terminal arborizations where it prolongs the sodium current thus giving rise to a repetitive response to single shocks applied to the nerve.", "contents": "Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat. When tityustoxin (TsTX, 1.43 muM; mol. wt. 6995) was applied to the rat phrenic nerve-diaphragm muscle preparation, both the directly and indirectly elicited muscle contractions were transiently potentiated by about 30 and 60%, respectively, and the half-relaxation time was prolonged to more than 10 times the control. The onset of potentiation of muscle contraction was immediate and coincided closely with the prolongation of the directly elicited action potential and depolarization of the muscle membrane but preceded the presynaptic effect of the toxin. TsTX antagonized the neuromuscular blockade produced by low concentrations of d-tubocurarine (6.5 muM) but not by higher concentrations of d-tubocurarine (13 muM) or by alpha-bungarotoxin (5 mug/ml). Single shocks to the nerve of toxin-treated muscles evoked repetitive end-plate potentials which summated and triggered action potentials and muscle contractions 15 minutes after exposure. After 25 minutes, the frequency of spontaneous transmitter release transiently increased from 2 to 550 sec-1 but was never blocked and there was no blockade of the acetylcholine receptors of chronically denervated muscle. Both the increase in miniature end-plate potential frequency and postsynaptic depolarization induced by TsTX could be blocked by tetrodotoxin, and the effects on end-plate potentials and action potentials could be blocked by lowering the external sodium concentration. Removal of calcium and addition of ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 10 mM) to the bathing fluid blocked the presynaptic but not postsynaptic effects of TsTX at 23 degrees C; at 37 degrees C the presynaptic effects of TsTX in a calcium-free medium with EGTA were depressed but still present. Delayed rectification and membrane electrical characteristics were unaffected by TsTX. The results indicate that TsTX depolarizes the pre- and postsynaptic membranes by increasing sodium permeability. The postsynaptic site of action is most likely to be the sarcolemmal membrane where TsTX delays Na inactivation and thus prolongs the active phase of muscle contraction. Presynaptically, TsTX has two sites of action: 1) it depolarizes the nerve terminal thus facilitating the spontaneous release of transmitter; and 2) it acts at the membrane of the unmyelinated nerve terminal arborizations where it prolongs the sodium current thus giving rise to a repetitive response to single shocks applied to the nerve."} {"id": "PMID:180279", "title": "Effects of ethacrynic acid and furosemide on isolated rat kidney mitochondria: inhibition of electron transport in the region of phosphorylation site II.", "content": "Previous reports that ethacrynic acid and furosemide inhibit the respiration of isolated mitochondria suggested a direct action of these diuretics on oxidative metabolism. To explore this possibility further, the effects of ethacrynic acid and furosemide on the oxygen consumption of mitochondria isolated from the cortex and outer medulla of rat kidneys were investigated. Both diuretics inhibited state 3 and uncoupled respiration supported by glutamate-malate (which enters the electron transport chain prior to site I) and succinate (which enters prior to site II); respiration supported by tetramethyl phenylene diamine-ascorbate (which enters prior to site III) was relatively unaffected. Biochemical bypass of site II significantly alleviated the respiratory inhibition by both agents. Confirmation of these findings was provided by measurement of the electron transport carriers by dual wavelength spectroscopy, which showed that both diuretics caused a reduction of flavoproteins and an oxidation of the cytochromes. It is concluded that ethacrynic acid and furosemide inhibit oxidative phosphorylation in vitro by inhibiting electron transport through phosphorylation site II.", "contents": "Effects of ethacrynic acid and furosemide on isolated rat kidney mitochondria: inhibition of electron transport in the region of phosphorylation site II. Previous reports that ethacrynic acid and furosemide inhibit the respiration of isolated mitochondria suggested a direct action of these diuretics on oxidative metabolism. To explore this possibility further, the effects of ethacrynic acid and furosemide on the oxygen consumption of mitochondria isolated from the cortex and outer medulla of rat kidneys were investigated. Both diuretics inhibited state 3 and uncoupled respiration supported by glutamate-malate (which enters the electron transport chain prior to site I) and succinate (which enters prior to site II); respiration supported by tetramethyl phenylene diamine-ascorbate (which enters prior to site III) was relatively unaffected. Biochemical bypass of site II significantly alleviated the respiratory inhibition by both agents. Confirmation of these findings was provided by measurement of the electron transport carriers by dual wavelength spectroscopy, which showed that both diuretics caused a reduction of flavoproteins and an oxidation of the cytochromes. It is concluded that ethacrynic acid and furosemide inhibit oxidative phosphorylation in vitro by inhibiting electron transport through phosphorylation site II."} {"id": "PMID:180280", "title": "The effect of parathyroidectomy and large doses of cholecalciferol on the ability of rats to adapt to changes in dietary intake of calcium.", "content": "1. Adaptation to different dietary levels of calcium was produced by feeding a low (0-2%) calcium diet or one of two high (1-6 or 0-8%) calcium diets for 4 or 6 weeks. Adaptive changes in true and apparent absorption of calcium, apparent absorption of phosphate and urinary excretion of calcium, were observed. 2. Parathyroidectomy performed prior to adaptation did not greatly impair the ability of rats to adapt to different levels of calcium in the diet. The response of the rats to parathyroidectomy was affected by their subsequent dietary history. 3. Six weeks after parathyroidectomy the plasma calcium was significantly higher than it had been immediately post-operatively. This rise in plasma calcium was seen in the rats adapted to the 1-6% calcium diet but not in those adapted to the 0-2% calcium diet. 4. Parathyroidectomy performed after adaptation had taken place did not abolish the adaptive changes. The response of rats to parathyroidectomy was affected by their previous dietary history. 5. Large doses of cholecalciferol given for 8 days after adaptation had taken place increased the absorption of calcium in rats adapted to the 0-8% calcium diet thereby abolishing or reducing the adaptive differences in absorption between these rats and rats adapted to the 0-2% calcium diet. The cholecalciferol increased urinary calcium excretion but did not abolish adaptive differences in urinary excretion of calcium between rats adapted to diets with different calcium levels. 6. It is concluded that parathyroid hormone does not play a major role in mediating adaptation to different dietary intakes of calcium. The possible role of 1-25 dihydroxycholecalciferol is discussed.", "contents": "The effect of parathyroidectomy and large doses of cholecalciferol on the ability of rats to adapt to changes in dietary intake of calcium. 1. Adaptation to different dietary levels of calcium was produced by feeding a low (0-2%) calcium diet or one of two high (1-6 or 0-8%) calcium diets for 4 or 6 weeks. Adaptive changes in true and apparent absorption of calcium, apparent absorption of phosphate and urinary excretion of calcium, were observed. 2. Parathyroidectomy performed prior to adaptation did not greatly impair the ability of rats to adapt to different levels of calcium in the diet. The response of the rats to parathyroidectomy was affected by their subsequent dietary history. 3. Six weeks after parathyroidectomy the plasma calcium was significantly higher than it had been immediately post-operatively. This rise in plasma calcium was seen in the rats adapted to the 1-6% calcium diet but not in those adapted to the 0-2% calcium diet. 4. Parathyroidectomy performed after adaptation had taken place did not abolish the adaptive changes. The response of rats to parathyroidectomy was affected by their previous dietary history. 5. Large doses of cholecalciferol given for 8 days after adaptation had taken place increased the absorption of calcium in rats adapted to the 0-8% calcium diet thereby abolishing or reducing the adaptive differences in absorption between these rats and rats adapted to the 0-2% calcium diet. The cholecalciferol increased urinary calcium excretion but did not abolish adaptive differences in urinary excretion of calcium between rats adapted to diets with different calcium levels. 6. It is concluded that parathyroid hormone does not play a major role in mediating adaptation to different dietary intakes of calcium. The possible role of 1-25 dihydroxycholecalciferol is discussed."} {"id": "PMID:180281", "title": "Synaptic transmission in parasympathetic ganglia in the urinary bladder of the cat.", "content": "1. Electrophysiological techniques were used to study the sacral para-sympathetic input to pelvic ganglia located on the surface of the urinary bladder of the cat. 2. Synaptic transmission in pelvic ganglia was mediated primarily via nicotinic receptors although muscarinic excitatory receptors were present. 3. The most prominent characteristic of transmission in pelvic ganglia was the marked recruitment elicited by increasing frequencies of preganglionic nerve stimulation. Post-ganglionic action potentials were of low amplitude at low frequencies of stimulation (0-1-0-5c/s), but commonly increased to five to twenty times control amplitudes during continuous stimulation at frequencies between 5 and 10c/s. Thus, it is proposed that vesical ganglia may act as \"filters\" in the micturition pathway; blocking the excitatory input to the bladder when intravesical pressure and parasympathetic firing is low and facilitating the neural input to the bladder during micturition when preganglionic activity is high. 4. Information was also obtained about the characteristics of the parasympathetic post-ganglionic neurones innervating the bladder. Stimulation of the preganglionic fibres in the pelvic nerve elicited a bimodal contraction consisting of an initial phasic response, which was atropine-resistant and a tonic response which was blocked by atropine. This suggests that two types of neurones, cholinergic and non-cholinergic, may mediate the sacral input to the vesical smooth muscle.", "contents": "Synaptic transmission in parasympathetic ganglia in the urinary bladder of the cat. 1. Electrophysiological techniques were used to study the sacral para-sympathetic input to pelvic ganglia located on the surface of the urinary bladder of the cat. 2. Synaptic transmission in pelvic ganglia was mediated primarily via nicotinic receptors although muscarinic excitatory receptors were present. 3. The most prominent characteristic of transmission in pelvic ganglia was the marked recruitment elicited by increasing frequencies of preganglionic nerve stimulation. Post-ganglionic action potentials were of low amplitude at low frequencies of stimulation (0-1-0-5c/s), but commonly increased to five to twenty times control amplitudes during continuous stimulation at frequencies between 5 and 10c/s. Thus, it is proposed that vesical ganglia may act as \"filters\" in the micturition pathway; blocking the excitatory input to the bladder when intravesical pressure and parasympathetic firing is low and facilitating the neural input to the bladder during micturition when preganglionic activity is high. 4. Information was also obtained about the characteristics of the parasympathetic post-ganglionic neurones innervating the bladder. Stimulation of the preganglionic fibres in the pelvic nerve elicited a bimodal contraction consisting of an initial phasic response, which was atropine-resistant and a tonic response which was blocked by atropine. This suggests that two types of neurones, cholinergic and non-cholinergic, may mediate the sacral input to the vesical smooth muscle."} {"id": "PMID:180283", "title": "[Fetal and neo-natal development of brown adipose tissue in guinea pigs and rats. Feto-maternal or milk transfer of essential fatty acids : lipogenesis and morphology (author's transl)].", "content": "Brown adipose tissue (BAT) lipogenesis (fatty acid, glycerol and CO2 synthesis) and its morphology determined by optical microscopy, were studied in guinea pigs and rats during intra-uterine life and during the suckling period. Following the receptor induction and after the commencement of the hormone sensitive adenylate-cyclase/lipase system (i.e. on the 60th day in guinea pigs, on the 20th day in rats), the fetal BAT releases fatty acids (NEFA) and is capable of allowing the non-shivering thermogenesis. When the maternal diet and, consequently, the fetal or neonatal BAT are supplied with considerable linoleic acid, NEFA contain a large proportion of essential fatty acids. In vitro, the greater the linoleic acid concentration in these NEFA, the less inhibited is the lipogenesis from (2-14C) pyruvate. Thus, in periods just preceding or succeeding birth, fatty acid and glycerol synthesis are higher when the feto-maternal and/or the milk supply are enriched in linoleic acid than when they contain a large proportion of endogenous fatty acids. Morphological studies indicate that the adipose cell evolution could be nonidentical in BAT more or less enriched in essential fatty acids. Linoleic enriched BAT (of animals born to females kept on a sunflower oil diet) seemed to be in a healthy physiological state at birth, perhaps due to rapid lipid renewal and synthesis in their membranes. The control BAT (of animals born to females kept on a lard diet) appeared loaded with fats and in a worse conservation state at the same age.", "contents": "[Fetal and neo-natal development of brown adipose tissue in guinea pigs and rats. Feto-maternal or milk transfer of essential fatty acids : lipogenesis and morphology (author's transl)]. Brown adipose tissue (BAT) lipogenesis (fatty acid, glycerol and CO2 synthesis) and its morphology determined by optical microscopy, were studied in guinea pigs and rats during intra-uterine life and during the suckling period. Following the receptor induction and after the commencement of the hormone sensitive adenylate-cyclase/lipase system (i.e. on the 60th day in guinea pigs, on the 20th day in rats), the fetal BAT releases fatty acids (NEFA) and is capable of allowing the non-shivering thermogenesis. When the maternal diet and, consequently, the fetal or neonatal BAT are supplied with considerable linoleic acid, NEFA contain a large proportion of essential fatty acids. In vitro, the greater the linoleic acid concentration in these NEFA, the less inhibited is the lipogenesis from (2-14C) pyruvate. Thus, in periods just preceding or succeeding birth, fatty acid and glycerol synthesis are higher when the feto-maternal and/or the milk supply are enriched in linoleic acid than when they contain a large proportion of endogenous fatty acids. Morphological studies indicate that the adipose cell evolution could be nonidentical in BAT more or less enriched in essential fatty acids. Linoleic enriched BAT (of animals born to females kept on a sunflower oil diet) seemed to be in a healthy physiological state at birth, perhaps due to rapid lipid renewal and synthesis in their membranes. The control BAT (of animals born to females kept on a lard diet) appeared loaded with fats and in a worse conservation state at the same age."} {"id": "PMID:180290", "title": "Inhibition by theophylline of phagocytosis in Acanthamoeba castellanii.", "content": "Theophylline inhibited the phagocytosis of latex beads by Acanthamoeba castellanii (Neff). The cells recovered the ability to engulf beads after 1-2 hr of exposure to theophylline. Cells which have been exposed to 25 mM theophylline for a period of inhibition and recovery were not inhibited further by incubation with a fresh medium containing the same concentration of theophylline. However, the medium in which the cells recovered was as effective as a fresh medium in inhibiting phagocytosis in a fresh batch of cells, suggesting that the development of insensitivity to theophylline inhibition resides with the cells themselves. Dibutyryl cyclic AMP also inhibited bead uptake.", "contents": "Inhibition by theophylline of phagocytosis in Acanthamoeba castellanii. Theophylline inhibited the phagocytosis of latex beads by Acanthamoeba castellanii (Neff). The cells recovered the ability to engulf beads after 1-2 hr of exposure to theophylline. Cells which have been exposed to 25 mM theophylline for a period of inhibition and recovery were not inhibited further by incubation with a fresh medium containing the same concentration of theophylline. However, the medium in which the cells recovered was as effective as a fresh medium in inhibiting phagocytosis in a fresh batch of cells, suggesting that the development of insensitivity to theophylline inhibition resides with the cells themselves. Dibutyryl cyclic AMP also inhibited bead uptake."} {"id": "PMID:180292", "title": "Genetic markers in atherosclerosis: a review.", "content": "There is a growing number of lipoprotein markers recognized by immunological, electrophoretic, and other biochemical methods, and a beginning has been made on studying their modes of inheritance and linkage relations. Suggestive but inconclusive evidence of a relation between the cerumen polymorphism and arteriosclerosis has been published. Associations of the ABO blood groups with cardiovascular disease and serum lipid levels have been established, but the exact relation to lipoproteins and atherosclerosis remains to be determined.", "contents": "Genetic markers in atherosclerosis: a review. There is a growing number of lipoprotein markers recognized by immunological, electrophoretic, and other biochemical methods, and a beginning has been made on studying their modes of inheritance and linkage relations. Suggestive but inconclusive evidence of a relation between the cerumen polymorphism and arteriosclerosis has been published. Associations of the ABO blood groups with cardiovascular disease and serum lipid levels have been established, but the exact relation to lipoproteins and atherosclerosis remains to be determined."} {"id": "PMID:180293", "title": "Trisomy 8 restricted to cultured fibroblasts.", "content": "In the course of re-examing cultured fibroblasts stored in liquid nitrogen from a patient with developmental retardation, solitary left kidney, and Wilms tumour, a cell line trisomic for chromosome 8 was found. Trisomy 8 was restricted to fibroblasts in the first 22 subcultures and was absent in later passages as well as in lymphocytes. A familial pericentric inversion of chromosome 2 was observed in three generations including the propositus but was though to be unrelated to the clinical problem. Multiple spontaneous chromosomal rearrangements were seen in several late subcultures.", "contents": "Trisomy 8 restricted to cultured fibroblasts. In the course of re-examing cultured fibroblasts stored in liquid nitrogen from a patient with developmental retardation, solitary left kidney, and Wilms tumour, a cell line trisomic for chromosome 8 was found. Trisomy 8 was restricted to fibroblasts in the first 22 subcultures and was absent in later passages as well as in lymphocytes. A familial pericentric inversion of chromosome 2 was observed in three generations including the propositus but was though to be unrelated to the clinical problem. Multiple spontaneous chromosomal rearrangements were seen in several late subcultures."} {"id": "PMID:180294", "title": "The isolation of reovirus-like agents (rota-viruses) from acute gastroenteritis of piglets.", "content": "Isolations of reovirus-like agents (rotaviruses) were made from nine of 23 outbreaks of piglet diarrhoea on different farms and from both weaned and unweaned piglets. The viruses were shown to be morphologically and anti-genically similar to the rotaviruses of children and calves. Gnotobiotig piglets given intranasal inoculations of five different isolates developed acute gastroenteritis, and the virus was re-isolated from the faeces or intestinal contents. The piglet virus was not adapted to replicate in cell culture. We conclude that the pig rotavirus is commonly associated with outbreaks of gastroenteritis and is probably an important aetiological factor in this disease.", "contents": "The isolation of reovirus-like agents (rota-viruses) from acute gastroenteritis of piglets. Isolations of reovirus-like agents (rotaviruses) were made from nine of 23 outbreaks of piglet diarrhoea on different farms and from both weaned and unweaned piglets. The viruses were shown to be morphologically and anti-genically similar to the rotaviruses of children and calves. Gnotobiotig piglets given intranasal inoculations of five different isolates developed acute gastroenteritis, and the virus was re-isolated from the faeces or intestinal contents. The piglet virus was not adapted to replicate in cell culture. We conclude that the pig rotavirus is commonly associated with outbreaks of gastroenteritis and is probably an important aetiological factor in this disease."} {"id": "PMID:180295", "title": "Fusion of phospholipid vesicles reconstituted with cytochrome c oxidase and mitochondrial hydrophobic protein.", "content": "Reconstituted cytochrome oxidase liposomes were fused with liposomes reconstituted with mitochondrial hydrophobic protein, which acts as a membrane-bound uncoupler of cytochrome oxidase. Fusion was assayed by the loss of respiratory control of cytochrome oxidase as measured by the increased rate of ascorbate oxidation induced by hydrophobic protein when both proteins shared the same vesicles. Fusion was dependent on the presence of phosphatidylserine in the liposomes Ca++ in the aqueous medium. Phosphatidylcholine-phosphatidylserine liposomes required higher concentrations of phosphatidylserine and Ca++ than did phosphatidylethanolamine-phosphatidylserine liposomes. Cytochrome oxidase vesicles containing high concentrations of phosphatidylserine showed little or no respiratory control, while those with lower concentrations showed high respiratory control; respiratory control could be induced by fusing cytochrome oxidase vesicles containing high phosphatidylserine with protein-free liposomes containing low phosphatidylserine concentration. If cytochrome oxidase vesicles and hydrophobic protein vesicles were prefused separately for 15 min, they lost the ability to fuse upon being subsequently mixed together. The reconstituted vesicles had diameters of about 200 A; fusion yielded vesicles with diameters in excess of 1000 A.", "contents": "Fusion of phospholipid vesicles reconstituted with cytochrome c oxidase and mitochondrial hydrophobic protein. Reconstituted cytochrome oxidase liposomes were fused with liposomes reconstituted with mitochondrial hydrophobic protein, which acts as a membrane-bound uncoupler of cytochrome oxidase. Fusion was assayed by the loss of respiratory control of cytochrome oxidase as measured by the increased rate of ascorbate oxidation induced by hydrophobic protein when both proteins shared the same vesicles. Fusion was dependent on the presence of phosphatidylserine in the liposomes Ca++ in the aqueous medium. Phosphatidylcholine-phosphatidylserine liposomes required higher concentrations of phosphatidylserine and Ca++ than did phosphatidylethanolamine-phosphatidylserine liposomes. Cytochrome oxidase vesicles containing high concentrations of phosphatidylserine showed little or no respiratory control, while those with lower concentrations showed high respiratory control; respiratory control could be induced by fusing cytochrome oxidase vesicles containing high phosphatidylserine with protein-free liposomes containing low phosphatidylserine concentration. If cytochrome oxidase vesicles and hydrophobic protein vesicles were prefused separately for 15 min, they lost the ability to fuse upon being subsequently mixed together. The reconstituted vesicles had diameters of about 200 A; fusion yielded vesicles with diameters in excess of 1000 A."} {"id": "PMID:180296", "title": "Oildroplets in the eyes of adult anuran amphibians: a comparative survey.", "content": "Oildroplets in the eyes of terrestrial vertebrates are spherical cellular organelles that stain for lipids, have no discernible internal structure, and often contain carotenoids and possibly other chemicals. A survey of 97 species of anuran amphibians (frogs and toads) revealed that all species of 16 families surveyed possessed yellow oildroplets of varying size in the cells of the pigment epithelium, except for three species that appear to have secondarily lost them during evolution. Furthermore, 25 species of six families also possess colorless oildroplets at the distal end of the inner segments of single cones and principal cones of the double-cone system; two species of the Ranidae appear to have secondarily lost such retinal oildroplets. Every species possesses epithelial or retinal oildroplets or both. Lastly, small oildroplet-like inclusions were discovered in the red blood cells of two species. All of Walls' ('42) summary generalizations about anuran oildroplets are incorrect: oildroplets are not restricted to the Ranidae, are not yellow when found in the cones, and do not correlate with photoactic behavior in 87 species. Evidence is reviewed suggesting that the primary function of anuran oildroplets is chemical storage, perhaps related to the visual pigment cycle. Oildroplets in the cones may additionally act as filters of ultraviolet radiation.", "contents": "Oildroplets in the eyes of adult anuran amphibians: a comparative survey. Oildroplets in the eyes of terrestrial vertebrates are spherical cellular organelles that stain for lipids, have no discernible internal structure, and often contain carotenoids and possibly other chemicals. A survey of 97 species of anuran amphibians (frogs and toads) revealed that all species of 16 families surveyed possessed yellow oildroplets of varying size in the cells of the pigment epithelium, except for three species that appear to have secondarily lost them during evolution. Furthermore, 25 species of six families also possess colorless oildroplets at the distal end of the inner segments of single cones and principal cones of the double-cone system; two species of the Ranidae appear to have secondarily lost such retinal oildroplets. Every species possesses epithelial or retinal oildroplets or both. Lastly, small oildroplet-like inclusions were discovered in the red blood cells of two species. All of Walls' ('42) summary generalizations about anuran oildroplets are incorrect: oildroplets are not restricted to the Ranidae, are not yellow when found in the cones, and do not correlate with photoactic behavior in 87 species. Evidence is reviewed suggesting that the primary function of anuran oildroplets is chemical storage, perhaps related to the visual pigment cycle. Oildroplets in the cones may additionally act as filters of ultraviolet radiation."} {"id": "PMID:180297", "title": "Evolutionary processes and evolutionary noise at the molecular level. II. A selectionist model for random fixations in proteins.", "content": "On account, notably, of a competition between different component functions for individual sites in polypeptide chains, each protein molecule represents a functional compromise, with some functions optimized, but the overall state of the molecule \"suboptimal\". The proposal is made that the selection coefficient relating to a protein molecule under given conditions can in principle be broken down into partial selection coefficients relevant to the different functions that the molecule carries out. At general-function sites, each fixation improves some function, while others deteriorate, at first nonsignificantly, and the overall adaptive state of the molecule fluctuates around its maximum. A selective mechanism is described whereby kaleidoscopic changes in primary structure at variable sites are indefinitely promoted, independently of any environmental changes and with the molecule remaining close to a state of maximal overall adaptation. The paradoxical aspect of this proposal is analyzed. The implication of specific functions in substitutions at general-function sites is noted. Further, it is shown that a certain category of changes in the internal environment of the organism can be integrated into the constant-environmental model for selection. Genetic sufficiency is considered a notion more adequate than genetic optimality for describing biological fitness and for providing a basis for the present model. On this basis selection occurs without genetic load. Multipolymorphism is one of the consequences. Several lines of evidence, in particular observations on polymorphism in deep sea organisms, seem to support the model. It is pointed out that it provides a theoretical foundation for a molecular evolutionary clock. The theoretical constancy of the clock depends on the constancy of functional density. The question of the evolution of functional density is examined. Comparisons of observed substitution frequencies with values expected on a random basis are rejected as a measure of the contribution to evolution of nondetermination. They are considered to reflect a hierarchy in the resistance of the molecules to different amino acid residues as substituents. A limited component of \"true\" randomness, again accompanied by selection, is on the other hand provided by the model. Most amino acid substitutions are considered evolutionary noise, even though noise compatible with selection. It is proposed that evolutionary significant substitutions may be identified by monitoring changes in functional density and weighted functional density.", "contents": "Evolutionary processes and evolutionary noise at the molecular level. II. A selectionist model for random fixations in proteins. On account, notably, of a competition between different component functions for individual sites in polypeptide chains, each protein molecule represents a functional compromise, with some functions optimized, but the overall state of the molecule \"suboptimal\". The proposal is made that the selection coefficient relating to a protein molecule under given conditions can in principle be broken down into partial selection coefficients relevant to the different functions that the molecule carries out. At general-function sites, each fixation improves some function, while others deteriorate, at first nonsignificantly, and the overall adaptive state of the molecule fluctuates around its maximum. A selective mechanism is described whereby kaleidoscopic changes in primary structure at variable sites are indefinitely promoted, independently of any environmental changes and with the molecule remaining close to a state of maximal overall adaptation. The paradoxical aspect of this proposal is analyzed. The implication of specific functions in substitutions at general-function sites is noted. Further, it is shown that a certain category of changes in the internal environment of the organism can be integrated into the constant-environmental model for selection. Genetic sufficiency is considered a notion more adequate than genetic optimality for describing biological fitness and for providing a basis for the present model. On this basis selection occurs without genetic load. Multipolymorphism is one of the consequences. Several lines of evidence, in particular observations on polymorphism in deep sea organisms, seem to support the model. It is pointed out that it provides a theoretical foundation for a molecular evolutionary clock. The theoretical constancy of the clock depends on the constancy of functional density. The question of the evolution of functional density is examined. Comparisons of observed substitution frequencies with values expected on a random basis are rejected as a measure of the contribution to evolution of nondetermination. They are considered to reflect a hierarchy in the resistance of the molecules to different amino acid residues as substituents. A limited component of \"true\" randomness, again accompanied by selection, is on the other hand provided by the model. Most amino acid substitutions are considered evolutionary noise, even though noise compatible with selection. It is proposed that evolutionary significant substitutions may be identified by monitoring changes in functional density and weighted functional density."} {"id": "PMID:180298", "title": "Empirical relationship between the number of nucleotide substitutions and interspecific identity of amino acid sequences in some proteins.", "content": "There are three different methods of estimating the number of nucleotide substitutions between a pair of species from amino acid sequence data, i.e. the Poisson correction method, random evolutionary hit method, and counting the actual but minimum number of nucleotide substitutions. In this paper the relationships among the estimates obtained by these methods are studied empirically. The results obtained indicate that there is a high correlation among these estimates and in practice any of the three methods may be used for constructing evolutionary trees or relating nucleotide substitutions to evolutionary time. The effects of varying rates of nucleotide substition among different sites on the Poisson correction and random evolutionary hit methods are also studied mathematically. It is shown that these two methods are quite insensitive to the variation of the rate of nucleotide substitution.", "contents": "Empirical relationship between the number of nucleotide substitutions and interspecific identity of amino acid sequences in some proteins. There are three different methods of estimating the number of nucleotide substitutions between a pair of species from amino acid sequence data, i.e. the Poisson correction method, random evolutionary hit method, and counting the actual but minimum number of nucleotide substitutions. In this paper the relationships among the estimates obtained by these methods are studied empirically. The results obtained indicate that there is a high correlation among these estimates and in practice any of the three methods may be used for constructing evolutionary trees or relating nucleotide substitutions to evolutionary time. The effects of varying rates of nucleotide substition among different sites on the Poisson correction and random evolutionary hit methods are also studied mathematically. It is shown that these two methods are quite insensitive to the variation of the rate of nucleotide substitution."} {"id": "PMID:180300", "title": "Gustatory sweating and related syndromes.", "content": "Gustatory sweating is a reflex, localized production of sweat associated with sight, smell, or ingestion of food. It involves most commonly the area of the auriculo-temporal nerve where it produces the well known Frey's syndrome. The pathophysiology of the syndrome is described with the aid of diagrams. Anatomically related syndromes are explained, namely the chorda tympani syndrome, crocodile tears, xerophthalmia of the suprageniculate facial nerve palsy, and the partial (otogenic) Horner's syndrome.", "contents": "Gustatory sweating and related syndromes. Gustatory sweating is a reflex, localized production of sweat associated with sight, smell, or ingestion of food. It involves most commonly the area of the auriculo-temporal nerve where it produces the well known Frey's syndrome. The pathophysiology of the syndrome is described with the aid of diagrams. Anatomically related syndromes are explained, namely the chorda tympani syndrome, crocodile tears, xerophthalmia of the suprageniculate facial nerve palsy, and the partial (otogenic) Horner's syndrome."} {"id": "PMID:180301", "title": "Avian arboviruses of the Witless Bay seabird Sanctuary, Newfoundland, Canada.", "content": "A virologic and serologic survey of arbovirus infections among seabirds and seabird ticks, Ixodes uriae, on Great Island. Witless Bay, Newfoundland, Canada, was conducted during 1971 and 1972. Kermerovo (Great Island, Bauline) and Sakhalin (Avalon) group viruses previously reported from birds and/or ticks on Great Island were prevalent among avian populations, while conclusive evidence of known nonindigenous serotypes was lacking. Circumstantial evidence-hemagglutination inhibiting antibody-of an unidentified member of the group B tick-borne encephalitis complex transmitted among marine birds of North America by I. uriae is reported. No evidence of human infections with any of these viruses was detected in a small number of biologists doing research on Great Island.", "contents": "Avian arboviruses of the Witless Bay seabird Sanctuary, Newfoundland, Canada. A virologic and serologic survey of arbovirus infections among seabirds and seabird ticks, Ixodes uriae, on Great Island. Witless Bay, Newfoundland, Canada, was conducted during 1971 and 1972. Kermerovo (Great Island, Bauline) and Sakhalin (Avalon) group viruses previously reported from birds and/or ticks on Great Island were prevalent among avian populations, while conclusive evidence of known nonindigenous serotypes was lacking. Circumstantial evidence-hemagglutination inhibiting antibody-of an unidentified member of the group B tick-borne encephalitis complex transmitted among marine birds of North America by I. uriae is reported. No evidence of human infections with any of these viruses was detected in a small number of biologists doing research on Great Island."} {"id": "PMID:180302", "title": "An outbreak of duck virus enteritis (duck plague) in Alberta.", "content": "Duck plague (Duck virus enteritis) was disgnosed in a resident population of Muscovy ducks (Cairina moschata) on a small game farm in Alberta. This disease has not been reported previously in Canada. Clinical signs consisted of cyanosis, depression and acute death. Necropsy of two Muscovy ducks revealed lesions typical of the disease. There were ulcerations with pseudomembranes in the small intestine, ulcerations with caseous plaques in the esophagus and eosinophilic intranuclear inclusion bodies in the spleen. Clinical disease with mortality was reproduced in young ducklings injected with tissue homogenates from field cases. All surviving inoculated ducklings seroconverted to highly significant titres of neutralizing antibodies to duck virus enteritis (DVE) virus. All attempts to isolate the agent in embryonating duck eggs or primary tissues cultures of duck and chicken kidney were negative. Identification of the DVE virus was accomplished by serum neutralization with ducklings as the host system.", "contents": "An outbreak of duck virus enteritis (duck plague) in Alberta. Duck plague (Duck virus enteritis) was disgnosed in a resident population of Muscovy ducks (Cairina moschata) on a small game farm in Alberta. This disease has not been reported previously in Canada. Clinical signs consisted of cyanosis, depression and acute death. Necropsy of two Muscovy ducks revealed lesions typical of the disease. There were ulcerations with pseudomembranes in the small intestine, ulcerations with caseous plaques in the esophagus and eosinophilic intranuclear inclusion bodies in the spleen. Clinical disease with mortality was reproduced in young ducklings injected with tissue homogenates from field cases. All surviving inoculated ducklings seroconverted to highly significant titres of neutralizing antibodies to duck virus enteritis (DVE) virus. All attempts to isolate the agent in embryonating duck eggs or primary tissues cultures of duck and chicken kidney were negative. Identification of the DVE virus was accomplished by serum neutralization with ducklings as the host system."} {"id": "PMID:180303", "title": "Nonhuman primate-associated viral hepatitis type A. Serologic evidence of hepatitis A virus infection.", "content": "Since 1961, viral hepatitis has been recognized as an occupational hazard among handlers of newly imported chimpanzees and other nonhuman primates. To determine whether previously reported cases were caused by human viral hepatitis type A, we tested paired serum samples from two outbreaks for antibody to hepatitis A antigen (anti-HA) by immune adherence hemagglutination (IAHA), recently available test. In both outbreaks, one of hepatitis transmitted from chimpanzee to man (Michigan, 1964), the second from chimpanzee to chimpanzee, man, and woolly monkey (Connecticut, 1971), serologic data documented recent hepatitis A virus infection among contacts-human and nonhuman primate-of implicated chimpanzees. This confirms serologically a previously noted epidemiologic association between nonhuman primate-associated hepatitis and human viral hepatitis, type A.", "contents": "Nonhuman primate-associated viral hepatitis type A. Serologic evidence of hepatitis A virus infection. Since 1961, viral hepatitis has been recognized as an occupational hazard among handlers of newly imported chimpanzees and other nonhuman primates. To determine whether previously reported cases were caused by human viral hepatitis type A, we tested paired serum samples from two outbreaks for antibody to hepatitis A antigen (anti-HA) by immune adherence hemagglutination (IAHA), recently available test. In both outbreaks, one of hepatitis transmitted from chimpanzee to man (Michigan, 1964), the second from chimpanzee to chimpanzee, man, and woolly monkey (Connecticut, 1971), serologic data documented recent hepatitis A virus infection among contacts-human and nonhuman primate-of implicated chimpanzees. This confirms serologically a previously noted epidemiologic association between nonhuman primate-associated hepatitis and human viral hepatitis, type A."} {"id": "PMID:180304", "title": "Hyperlipidemia due to oxymetholone therapy. Occurrence in a long-term hemodialysis patient.", "content": "Marked hypertriglyceridemia and hypercholesterolemia accompanied by angina and a left cerebral thrombosis occurred in a long-term hemodialysis patient following 5 1/2 weeks of oral treatment with oxymetholone, 100 mg/day, a synthetic androgen. After androgen therapy was discontinued, over a three-month period, plasma lipid values progressively decreased below pretreatment values, and clinical symptoms disappeared. During rechallenge with oxymetholone, serum lipid values increased substantially, and the lipoprotein pattern changed from a type IV to a type V. Detailed lipid studies showed subnormal postheparin lipolytic activity and a fast-migrating pre-beta-lipoprotein in a very-low-density lipoproteins (VLDL) fraction. Because of the data linking lipid abnormalities to atherosclerosis and the acceleration of atherosclerosis in long-term hemodialysis patients, great caution should be exercised in administering androgenic steroids to these patients.", "contents": "Hyperlipidemia due to oxymetholone therapy. Occurrence in a long-term hemodialysis patient. Marked hypertriglyceridemia and hypercholesterolemia accompanied by angina and a left cerebral thrombosis occurred in a long-term hemodialysis patient following 5 1/2 weeks of oral treatment with oxymetholone, 100 mg/day, a synthetic androgen. After androgen therapy was discontinued, over a three-month period, plasma lipid values progressively decreased below pretreatment values, and clinical symptoms disappeared. During rechallenge with oxymetholone, serum lipid values increased substantially, and the lipoprotein pattern changed from a type IV to a type V. Detailed lipid studies showed subnormal postheparin lipolytic activity and a fast-migrating pre-beta-lipoprotein in a very-low-density lipoproteins (VLDL) fraction. Because of the data linking lipid abnormalities to atherosclerosis and the acceleration of atherosclerosis in long-term hemodialysis patients, great caution should be exercised in administering androgenic steroids to these patients."} {"id": "PMID:180305", "title": "Neuromyelitis optica (relapsing type).", "content": "A case of relapsing type of neuromyelitis optica following influenza-like illness treated successfully with steroids and corticotrophin has been described. Raised gamma-globulin in CSF was suggestive of an autoimmune disorder. Inspite of six relapses in 8 years she has minimal neurological deficit.", "contents": "Neuromyelitis optica (relapsing type). A case of relapsing type of neuromyelitis optica following influenza-like illness treated successfully with steroids and corticotrophin has been described. Raised gamma-globulin in CSF was suggestive of an autoimmune disorder. Inspite of six relapses in 8 years she has minimal neurological deficit."} {"id": "PMID:180310", "title": "Lipids and lipoproteins of serum and organ tissues in a case of familial hyperlipoproteinemia type II.", "content": "Lipids and lipoproteins of serum and various organ tissues of a patient with familial hyperlipoproteinemia homozygous Type II were studied. It was found that low density lipoprotein between densities of 1.006 and 1.063 was a major component of serum of the patient. The isolated low density lipoprotein appeared to be rather similar to that of normal human serum from the viewpoints of chemical composition and physico-chemical properties. Antibody against the low density lipoprotein of the patient reacted not only with the same lipoprotein, but also with normal human low density lipoproteins. Immunoelectrophoresis of the antibody gave a single precipitin line against only the low density lipoprotein. Immunofluorescent techniques using the fluorescein labeled antibody showed localization of low density lipoprotein in cytoplasm of hepatocytes of both the patient and other human. No fluorescences were found in other organ cells except in their capillary tubes and renal glomerulus in the hyperlipoproteinemia Type II. It was noted that tuberous xanthomata contained fairly large amounts of cholesterol and cholesterol ester. Fatty acid composition of neutral lipids and phospholipids from the serum low density lipoprotein, xanthomata, liver and other organ tissues were compared with each other. Chomesterol ester of the xanthomata contained much smaller amounts of polyunsaturated fatty acids as compared with those of the low density lipoprotein and other tissue. Also, composition of free fatty acids in liver differed from those of other tissues.", "contents": "Lipids and lipoproteins of serum and organ tissues in a case of familial hyperlipoproteinemia type II. Lipids and lipoproteins of serum and various organ tissues of a patient with familial hyperlipoproteinemia homozygous Type II were studied. It was found that low density lipoprotein between densities of 1.006 and 1.063 was a major component of serum of the patient. The isolated low density lipoprotein appeared to be rather similar to that of normal human serum from the viewpoints of chemical composition and physico-chemical properties. Antibody against the low density lipoprotein of the patient reacted not only with the same lipoprotein, but also with normal human low density lipoproteins. Immunoelectrophoresis of the antibody gave a single precipitin line against only the low density lipoprotein. Immunofluorescent techniques using the fluorescein labeled antibody showed localization of low density lipoprotein in cytoplasm of hepatocytes of both the patient and other human. No fluorescences were found in other organ cells except in their capillary tubes and renal glomerulus in the hyperlipoproteinemia Type II. It was noted that tuberous xanthomata contained fairly large amounts of cholesterol and cholesterol ester. Fatty acid composition of neutral lipids and phospholipids from the serum low density lipoprotein, xanthomata, liver and other organ tissues were compared with each other. Chomesterol ester of the xanthomata contained much smaller amounts of polyunsaturated fatty acids as compared with those of the low density lipoprotein and other tissue. Also, composition of free fatty acids in liver differed from those of other tissues."} {"id": "PMID:180311", "title": "Serum lipoprotein profile in infectious hepatitis.", "content": "There is absence of pre-beta and alpha-lipoproteins in the acute stage of infectious hepatitis. With improvement both clinically and biochemically there is appearance of both lipoproteins, with complete reversal to normal lipoprotein pattern in the end.", "contents": "Serum lipoprotein profile in infectious hepatitis. There is absence of pre-beta and alpha-lipoproteins in the acute stage of infectious hepatitis. With improvement both clinically and biochemically there is appearance of both lipoproteins, with complete reversal to normal lipoprotein pattern in the end."} {"id": "PMID:180312", "title": "Response of nude mice to a mouse hepatitis virus isolated from a wasting nude mouse.", "content": "Chronic active hepatitis was produced in nude mice after inoculation with a mouse hepatitis virus from a natural nude case which was incapable of causing fatal infection in haired heterozygous mice without cortisone. Survival time of infected nude mice varied greatly from 1 to 10 weeks after the inoculation. Degeneration and necrosis of hepatocytes, apparition of small and megalocytic hepatocytes, and infiltration of lymphocytes and plasma cells with fibrosis, were most remarkable in those which died 3 weeks or more after inoculation. No such severe hepatic lesions were recognized in heterozygous haired litter-mates after inoculation of the same virus. Necrotic lesions with poor inflammatory reactions were seen in the brain of all infected and dead nude mice, while some cerebral lesions with apparent perivascular infiltration were detected in heterozygous ones only at early stage of infection.", "contents": "Response of nude mice to a mouse hepatitis virus isolated from a wasting nude mouse. Chronic active hepatitis was produced in nude mice after inoculation with a mouse hepatitis virus from a natural nude case which was incapable of causing fatal infection in haired heterozygous mice without cortisone. Survival time of infected nude mice varied greatly from 1 to 10 weeks after the inoculation. Degeneration and necrosis of hepatocytes, apparition of small and megalocytic hepatocytes, and infiltration of lymphocytes and plasma cells with fibrosis, were most remarkable in those which died 3 weeks or more after inoculation. No such severe hepatic lesions were recognized in heterozygous haired litter-mates after inoculation of the same virus. Necrotic lesions with poor inflammatory reactions were seen in the brain of all infected and dead nude mice, while some cerebral lesions with apparent perivascular infiltration were detected in heterozygous ones only at early stage of infection."} {"id": "PMID:180313", "title": "Clostridium perfringens exotoxins. IV. Inhibition of the theta-toxin induced hemolysis by steroids and related compounds.", "content": "1. The inhibitory powers of thirty two samples of steroids and their related compounds on the theta-toxin induced hemolysis were assayed. Apparent I50 value of cholesterol, the most potent inhibitor amoung them, was 0.022 muM. 2. Inhibitory powers of sterol acetates were not more than one tenth of those of the corresponding sterol, and steroids without 3-hydroxyl group hardly inhibited the hemolysis. These results suggest that 3-hydroxyl group of sterols plays an important role in the inhibition. 3. The inhibitory power of sterols were strongly affected by steric situation of 3-hydroxyl group for the face of their tetracyclic rings. From these results it is suggested that theta-toxin binds to beta-side of the tetracyclic rings but not to alpha-side. 4. A methylsterol and pentacyclic triterpens with 3-hydroxyl group also inhibited the hemolysis, but steroids and their related compounds either with a hydrophylic or without a hydrophobic group at their ring D had little, if any, inhibitory power.", "contents": "Clostridium perfringens exotoxins. IV. Inhibition of the theta-toxin induced hemolysis by steroids and related compounds. 1. The inhibitory powers of thirty two samples of steroids and their related compounds on the theta-toxin induced hemolysis were assayed. Apparent I50 value of cholesterol, the most potent inhibitor amoung them, was 0.022 muM. 2. Inhibitory powers of sterol acetates were not more than one tenth of those of the corresponding sterol, and steroids without 3-hydroxyl group hardly inhibited the hemolysis. These results suggest that 3-hydroxyl group of sterols plays an important role in the inhibition. 3. The inhibitory power of sterols were strongly affected by steric situation of 3-hydroxyl group for the face of their tetracyclic rings. From these results it is suggested that theta-toxin binds to beta-side of the tetracyclic rings but not to alpha-side. 4. A methylsterol and pentacyclic triterpens with 3-hydroxyl group also inhibited the hemolysis, but steroids and their related compounds either with a hydrophylic or without a hydrophobic group at their ring D had little, if any, inhibitory power."} {"id": "PMID:180314", "title": "Cell lines established from (BALB/cx DBA/2)F1 mice which show parent type susceptibility to murine leukemia viruses.", "content": "The susceptibility to two tissue culture cell lines established from (BALB/cx DBA/2)F1 (CDF1) mice to murine leukemia viruses (MLVs) was compared with those of various cell lines. While embryo cells of CDF1 mice were resistant to both N- and B- tropic MLVs, one cell line was susceptible to N-tropic MLV and the other to B-tropic MLV. So the cell lines of CDF1 mice had not the same susceptibility to MLVs as CDF1 embryo cells had. Cell lines established from N- and B-type inbred mice had kept their original susceptibility to MLVs. These results suggested the phenotype of some F1 hybrid mouse cells tended to change into either parental type after establishment as cell lines.", "contents": "Cell lines established from (BALB/cx DBA/2)F1 mice which show parent type susceptibility to murine leukemia viruses. The susceptibility to two tissue culture cell lines established from (BALB/cx DBA/2)F1 (CDF1) mice to murine leukemia viruses (MLVs) was compared with those of various cell lines. While embryo cells of CDF1 mice were resistant to both N- and B- tropic MLVs, one cell line was susceptible to N-tropic MLV and the other to B-tropic MLV. So the cell lines of CDF1 mice had not the same susceptibility to MLVs as CDF1 embryo cells had. Cell lines established from N- and B-type inbred mice had kept their original susceptibility to MLVs. These results suggested the phenotype of some F1 hybrid mouse cells tended to change into either parental type after establishment as cell lines."} {"id": "PMID:180315", "title": "Elevated levels of IgE antibodies to ascaris and mite antigens in Papua New Guinea.", "content": "Levels of IgE as well as specific IgE antibodies to ascaris and mite have been studied in two groups in Papua New Guinea (PNG), patients with primary liver carcinoma (PLC) and normal blood donors, and in two groups in Japan, normal subjects and asthmatic patients. A radioallergosorbent test was used to measure IgE antibodies to ascaris and mite antigens. Much higher levels of IgE were found in the Papua New Guinean subjects than the normal Japanese subjects. Also levels of IgE antibodies to ascaris were much higher in Papua New Guineans than in the Japanese subjects. Though similar results were observed in IgE antibodies to mite, difference between normal Papua New Guineans and normal Japanese was small, whereas difference between the patients with PLC in PNG and the normal Japanese subjects was very large. Highest levels of IgE antibodies to mite were detected in Japanese with asthma. No correlations were observed among IgE levels, levels of IgE antibodies to ascaris and levels of IgE antibodies to mite. It is concluded that both ascaris and mite IgE antibodies contribute the very high levels of IgE seen in Papua New Guineans, but many other factors may be operative.", "contents": "Elevated levels of IgE antibodies to ascaris and mite antigens in Papua New Guinea. Levels of IgE as well as specific IgE antibodies to ascaris and mite have been studied in two groups in Papua New Guinea (PNG), patients with primary liver carcinoma (PLC) and normal blood donors, and in two groups in Japan, normal subjects and asthmatic patients. A radioallergosorbent test was used to measure IgE antibodies to ascaris and mite antigens. Much higher levels of IgE were found in the Papua New Guinean subjects than the normal Japanese subjects. Also levels of IgE antibodies to ascaris were much higher in Papua New Guineans than in the Japanese subjects. Though similar results were observed in IgE antibodies to mite, difference between normal Papua New Guineans and normal Japanese was small, whereas difference between the patients with PLC in PNG and the normal Japanese subjects was very large. Highest levels of IgE antibodies to mite were detected in Japanese with asthma. No correlations were observed among IgE levels, levels of IgE antibodies to ascaris and levels of IgE antibodies to mite. It is concluded that both ascaris and mite IgE antibodies contribute the very high levels of IgE seen in Papua New Guineans, but many other factors may be operative."} {"id": "PMID:180316", "title": "Effects of cytochalasin B and dibutyryl cyclic AMP on intraleukocytic bactericidal activity.", "content": "Cytochalasin B (CB) is known to regulate the movement of intracellular microfilaments system. In this experiment, the effect of CB on the intraleukocytic bactericidal activity was first studied and concluded that CB inhibited the intracellular bactericidal activity remarkably. Addition of CB resulted in increased nitroblue tetrazolium (NBT)-dye reduction, while the specific activities of glucose-6-phosphate dehydrogenase (G-6-PD) and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase of CB-treated neutrophils exhibited within the normal range. But the uptake of Glucose-1-14C or -6-14C was markedly inhibited by CB treatment. However, the following substances inhibited NBT-dye reduction in decreasing order: cyclic adenosine 3', 5'-monophosphate (cAMP), N6-O2' dibutyryl cyclic adenosine 3', 5'-monophosphate (DBcAMP), prostaglandin F2alpha (PGF2alpha) and prostaglandin E1 (PGE1). These drugs also decreased hexose monophosphate shunt (HMS) enzyme activities. Addition of CB and DBcAMP decreased the intracellular bactericidal activity of neutrophils. But CB had no effect on intracellular levels of cAMP. From the results obtained, it is likely that intracellular bactericidal phenomena of human neutrophils are controlled by cyclic AMP cascades and by the microfilaments system, separately.", "contents": "Effects of cytochalasin B and dibutyryl cyclic AMP on intraleukocytic bactericidal activity. Cytochalasin B (CB) is known to regulate the movement of intracellular microfilaments system. In this experiment, the effect of CB on the intraleukocytic bactericidal activity was first studied and concluded that CB inhibited the intracellular bactericidal activity remarkably. Addition of CB resulted in increased nitroblue tetrazolium (NBT)-dye reduction, while the specific activities of glucose-6-phosphate dehydrogenase (G-6-PD) and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase of CB-treated neutrophils exhibited within the normal range. But the uptake of Glucose-1-14C or -6-14C was markedly inhibited by CB treatment. However, the following substances inhibited NBT-dye reduction in decreasing order: cyclic adenosine 3', 5'-monophosphate (cAMP), N6-O2' dibutyryl cyclic adenosine 3', 5'-monophosphate (DBcAMP), prostaglandin F2alpha (PGF2alpha) and prostaglandin E1 (PGE1). These drugs also decreased hexose monophosphate shunt (HMS) enzyme activities. Addition of CB and DBcAMP decreased the intracellular bactericidal activity of neutrophils. But CB had no effect on intracellular levels of cAMP. From the results obtained, it is likely that intracellular bactericidal phenomena of human neutrophils are controlled by cyclic AMP cascades and by the microfilaments system, separately."} {"id": "PMID:180322", "title": "Effects of various agents on synaptosomal adenylate cyclase activity in the absence and presence of the boiled supernatant.", "content": "A study was made of the effects of various agents on adenylate cyclase in synaptosomes in both the absence and presence of the boiled supernatant from rat cerebral cortex. The activity of adenylate cyclase in these preparations was inhibited by the sulfhydryl reactive agent p-chloromercuribenzoate. Sulfhydryl compounds such cysteine, glutathione and Coenzyme A stimulated the enzymic activity in both the absence and presence of the boiled supernatant. The chelating agent 1.2-bis-(2-dicarboxymethylaminoethoxy)ethane caused a stimulation of the enzymic activity with and without the presence of the boiled supernatant. Adenine nucleotide (adenine, adenosine, AMP and ADP), GTP, Pi and carbamylcholine seemed to have little effect. The stimulatory substance in the boiled supernatant was estimated to have a molecular weight in the range of 1,000-1,300.", "contents": "Effects of various agents on synaptosomal adenylate cyclase activity in the absence and presence of the boiled supernatant. A study was made of the effects of various agents on adenylate cyclase in synaptosomes in both the absence and presence of the boiled supernatant from rat cerebral cortex. The activity of adenylate cyclase in these preparations was inhibited by the sulfhydryl reactive agent p-chloromercuribenzoate. Sulfhydryl compounds such cysteine, glutathione and Coenzyme A stimulated the enzymic activity in both the absence and presence of the boiled supernatant. The chelating agent 1.2-bis-(2-dicarboxymethylaminoethoxy)ethane caused a stimulation of the enzymic activity with and without the presence of the boiled supernatant. Adenine nucleotide (adenine, adenosine, AMP and ADP), GTP, Pi and carbamylcholine seemed to have little effect. The stimulatory substance in the boiled supernatant was estimated to have a molecular weight in the range of 1,000-1,300."} {"id": "PMID:180319", "title": "Japanese encephalitis surveillance in China (Province of Taiwan) during 1968-1971. I. Geographical and seasonal features of case outbreaks.", "content": "During 1968-1971 Japanese encephalitis (JE) surveillance was conducted with WHO-assisted programs in Taiwan area. Emphasis was placed on: (1) active case-finding by hospital visits; (2) blood collection from every patient at the suitable time; and (3) the enforcement of standard diagnostic criteria on the results of hemagglutination-inhibition tests. Each year, approximately 90% of reported patients were etiologically examined. JE virus etiology was established in 277 (1968), 279 (1969), 269 (1970) and 158 (1971) cases. Despite the apparent concentration of cases in several cities, practically all the cultivated plains and basins were established as potentially endemic for JE. JE outbreak is found to have been clearly associated with season, not only in subtropical but also in tropical Taiwan. Each year it occurred consistently in mid-July in the southernmost county, 2-3 weeks after the peak of rice transplantation and its duration was a few weeks. On the western side of the island, although less consistently, JE outbreak seems to occur one to three weeks later than in the south. Outbreak in eastern Taiwan was a mid-September phenomenon for 3 years. Observed seasonal lag, which was significant between two neighboring localities on same latitude, suggests that paddy water management is more directly related to date of outbreak than local climate. Seasonal characteristics further suggests that the area may be separated into eight ecologic subdivisions. JE-virus transmission to a man during April at temperatures below the average of 20 C was discussed.", "contents": "Japanese encephalitis surveillance in China (Province of Taiwan) during 1968-1971. I. Geographical and seasonal features of case outbreaks. During 1968-1971 Japanese encephalitis (JE) surveillance was conducted with WHO-assisted programs in Taiwan area. Emphasis was placed on: (1) active case-finding by hospital visits; (2) blood collection from every patient at the suitable time; and (3) the enforcement of standard diagnostic criteria on the results of hemagglutination-inhibition tests. Each year, approximately 90% of reported patients were etiologically examined. JE virus etiology was established in 277 (1968), 279 (1969), 269 (1970) and 158 (1971) cases. Despite the apparent concentration of cases in several cities, practically all the cultivated plains and basins were established as potentially endemic for JE. JE outbreak is found to have been clearly associated with season, not only in subtropical but also in tropical Taiwan. Each year it occurred consistently in mid-July in the southernmost county, 2-3 weeks after the peak of rice transplantation and its duration was a few weeks. On the western side of the island, although less consistently, JE outbreak seems to occur one to three weeks later than in the south. Outbreak in eastern Taiwan was a mid-September phenomenon for 3 years. Observed seasonal lag, which was significant between two neighboring localities on same latitude, suggests that paddy water management is more directly related to date of outbreak than local climate. Seasonal characteristics further suggests that the area may be separated into eight ecologic subdivisions. JE-virus transmission to a man during April at temperatures below the average of 20 C was discussed."} {"id": "PMID:180320", "title": "Japanese encephalitis surveillance in China (Province of Taiwan) during 1968-1971. II. Age-secific incidence in connection with Japanese encephalitis vaccination program.", "content": "A baseline age/morbidity pattern for Japanese encephalitis (JE) epidemic in China (Province of Taiwan) in the 1960s was sought in JE surveillance. The pattern is characterized by: (1) high incidence in age groups 2-4 years, (2) moderately high incidence in age groups 5-7 years, (3) negligible incidence in children under 1 year of age as well as in adults, and (4) the variability of relative height of peak incidence co-incident with the JE-epidemic size in situ. Concurrently with surveillance, a JE-vaccination program was implemented by the Government. The children of target age groups received two doses of vaccine each during April. Vigilant supervision was given to the campaign to achieve a high coverage rate with two-dose vaccination and meticulous record-keeping. During 1969-1972, 2-year olds were the exclusive target; 52.2% (1969), 71.5% (1970), 74.5% (1971), and 83.0% (1972) of the target age group were covered. A considerable change from the baseline age/morbidity pattern seen in 1968 occurred during the above period. The comparison of epidemicity-adjusted incidence by year indications that incidence reduction in the 2- and 3-year old children in 1971 were substantial and suggests the possible impact of vaccination. The total JE incidence for the period 1968-1971 appears to be much lower in vaccinated population (23 reported and 8 confirmed/0.9 million) than in unvaccinated population (1,330 reported and 679 confirmed/2.2 million).", "contents": "Japanese encephalitis surveillance in China (Province of Taiwan) during 1968-1971. II. Age-secific incidence in connection with Japanese encephalitis vaccination program. A baseline age/morbidity pattern for Japanese encephalitis (JE) epidemic in China (Province of Taiwan) in the 1960s was sought in JE surveillance. The pattern is characterized by: (1) high incidence in age groups 2-4 years, (2) moderately high incidence in age groups 5-7 years, (3) negligible incidence in children under 1 year of age as well as in adults, and (4) the variability of relative height of peak incidence co-incident with the JE-epidemic size in situ. Concurrently with surveillance, a JE-vaccination program was implemented by the Government. The children of target age groups received two doses of vaccine each during April. Vigilant supervision was given to the campaign to achieve a high coverage rate with two-dose vaccination and meticulous record-keeping. During 1969-1972, 2-year olds were the exclusive target; 52.2% (1969), 71.5% (1970), 74.5% (1971), and 83.0% (1972) of the target age group were covered. A considerable change from the baseline age/morbidity pattern seen in 1968 occurred during the above period. The comparison of epidemicity-adjusted incidence by year indications that incidence reduction in the 2- and 3-year old children in 1971 were substantial and suggests the possible impact of vaccination. The total JE incidence for the period 1968-1971 appears to be much lower in vaccinated population (23 reported and 8 confirmed/0.9 million) than in unvaccinated population (1,330 reported and 679 confirmed/2.2 million)."} {"id": "PMID:180327", "title": "Evolution of the digestive microflora in a unit of specified-pathogen-free mice: efficiency of the barrier.", "content": "RhoIco strain], barrier-maintained since 1970, is described. Some \"contaminants\" appeared spontaneously during the period 1971-1973, but microorganisms belonging to the genera Lactobacillus Streptococcus, Enterobacteria, Escherichia and Bacillus remained stable. The methods of investigation used were not suitable for the assessment of strictly anaerobic strains. The stability of the digestive microflora durine the last 2 years of this study is believed to be related to the skill and conscientiousness of the technicians responsible for the daily care of these mice.", "contents": "Evolution of the digestive microflora in a unit of specified-pathogen-free mice: efficiency of the barrier. RhoIco strain], barrier-maintained since 1970, is described. Some \"contaminants\" appeared spontaneously during the period 1971-1973, but microorganisms belonging to the genera Lactobacillus Streptococcus, Enterobacteria, Escherichia and Bacillus remained stable. The methods of investigation used were not suitable for the assessment of strictly anaerobic strains. The stability of the digestive microflora durine the last 2 years of this study is believed to be related to the skill and conscientiousness of the technicians responsible for the daily care of these mice."} {"id": "PMID:180328", "title": "Renomedullary interstitial cells in the spontaneously hypertensive rat.", "content": "Renomedullary interstitial cells (RIC) are known to synthesize and release prostaglandins which may play a significant role in the development or severity of hypertension. The medulla of the spontaneously hypertensive rat contains RIC which are morphologically very similar to those previously described in the normotensive rat. The granularity of the RIC, however, was increased in the spontaneously hypertensive rat compared to normotensive Wistars (9.6 +/- 2.34 versus 5.3 +/- 2.05 granules per cell, respectively, p less than 0.001) or treated spontaneously hypertensive rats (7.2 +/- 1.65 granules per cell, p less than 0.001). Granule counts also increased in the presence of mild and moderate degrees of renal arteriolar sclerosis, but decreased in long standing hypertension with more severe and extensive lesions involving both arteries and arterioles. These results are consistent with the hypothesis that the RIC respond to an elevation of blood pressure in the spontaneously hypertensive rats by increased release of antihypertensive substances. In addition, the decrease in granularity of the RIC in the presence of extensive renal arteriolar and arterial damage suggests reduced ability to compensate for the elevated blood pressure and thus may contribute to the acceleration of hypertension.", "contents": "Renomedullary interstitial cells in the spontaneously hypertensive rat. Renomedullary interstitial cells (RIC) are known to synthesize and release prostaglandins which may play a significant role in the development or severity of hypertension. The medulla of the spontaneously hypertensive rat contains RIC which are morphologically very similar to those previously described in the normotensive rat. The granularity of the RIC, however, was increased in the spontaneously hypertensive rat compared to normotensive Wistars (9.6 +/- 2.34 versus 5.3 +/- 2.05 granules per cell, respectively, p less than 0.001) or treated spontaneously hypertensive rats (7.2 +/- 1.65 granules per cell, p less than 0.001). Granule counts also increased in the presence of mild and moderate degrees of renal arteriolar sclerosis, but decreased in long standing hypertension with more severe and extensive lesions involving both arteries and arterioles. These results are consistent with the hypothesis that the RIC respond to an elevation of blood pressure in the spontaneously hypertensive rats by increased release of antihypertensive substances. In addition, the decrease in granularity of the RIC in the presence of extensive renal arteriolar and arterial damage suggests reduced ability to compensate for the elevated blood pressure and thus may contribute to the acceleration of hypertension."} {"id": "PMID:180329", "title": "Uptake of circulating iron by the duodenum of normal mice and mice with altered iron stores, including sex-linked anemia: high resolution radioautographic study.", "content": "Using electron microscopy radioautography, the deposition of intravenously administered iron in the duodenal epithelium was studied in normal mice, iron-overloaded and iron-deficient mice, and in mice with X-linked anemia (gene symbol sla) 4 and 24 hours after injection of 59Fe. The resolution of radioautography with 59Fe was determined with a line source and the distance from the hot line within which half of the grains fell (HD value) was 1650 A. In normal, iron-overloaded, and sla mice, radioiron was localized in the undifferentiated crypt cells at 4 hours and in the absorptive cells of the luminal half of the villi, at 24 hours. At both times, the vast majority of the grains was seen over the areas rich in free ribosomes and rough endoplasmic reticulum. In iron-deficient mice, grains were not found at either time. The amount of iron incorporated in the crypt cells was related to the size of the body iron stores. It is postulated that the amount of iron incorporated in the crypt cells is the result of interaction between uptake and return to the blood of the circulating iron. Once the crypt cells have differentiated into absorptive cells, the uptake and recirculation of iron from and to the blood would cease, leaving an amount of \"message\" iron which determines the absorptive cell's subsequent capacity for iron transfer to the plasma. In sla mice, in spite of tissue iron deficiency, the amount of iron deposited was similar to that of normal mice and markedly increased after treatment of the anemia. The accumulation of iron in the crypt cells may result from the decreased return to the blood of the incorporated circulating iron, due to the postulated deficient iron carrier mechanism in sla, or may be a consequence of increased avidity of the absorptive cells for circulating iron. In either event, the result would be that the absorptive cell receives an inappropriate message with resulting inappropriate absorption of iron.", "contents": "Uptake of circulating iron by the duodenum of normal mice and mice with altered iron stores, including sex-linked anemia: high resolution radioautographic study. Using electron microscopy radioautography, the deposition of intravenously administered iron in the duodenal epithelium was studied in normal mice, iron-overloaded and iron-deficient mice, and in mice with X-linked anemia (gene symbol sla) 4 and 24 hours after injection of 59Fe. The resolution of radioautography with 59Fe was determined with a line source and the distance from the hot line within which half of the grains fell (HD value) was 1650 A. In normal, iron-overloaded, and sla mice, radioiron was localized in the undifferentiated crypt cells at 4 hours and in the absorptive cells of the luminal half of the villi, at 24 hours. At both times, the vast majority of the grains was seen over the areas rich in free ribosomes and rough endoplasmic reticulum. In iron-deficient mice, grains were not found at either time. The amount of iron incorporated in the crypt cells was related to the size of the body iron stores. It is postulated that the amount of iron incorporated in the crypt cells is the result of interaction between uptake and return to the blood of the circulating iron. Once the crypt cells have differentiated into absorptive cells, the uptake and recirculation of iron from and to the blood would cease, leaving an amount of \"message\" iron which determines the absorptive cell's subsequent capacity for iron transfer to the plasma. In sla mice, in spite of tissue iron deficiency, the amount of iron deposited was similar to that of normal mice and markedly increased after treatment of the anemia. The accumulation of iron in the crypt cells may result from the decreased return to the blood of the incorporated circulating iron, due to the postulated deficient iron carrier mechanism in sla, or may be a consequence of increased avidity of the absorptive cells for circulating iron. In either event, the result would be that the absorptive cell receives an inappropriate message with resulting inappropriate absorption of iron."} {"id": "PMID:180353", "title": "The existance of a group translocation transport mechanism in animal cells: uptake of the ribose moiety of inosine.", "content": "After exposure to inosine, transport-competent plasma membrane vesicles isolated from SV-40-transformed Bal/c 3T3 cells accumulate intravesicular ribose 1-PO4 at a concentration 200-fold greater than the extravesicular concentration. An analysis of the purine nucleoside phosphorylase activity distribution in various subcellular fractions, relative to other enzyme activities, indicated the presence of plasma membrane-associated purine nucleoside phosphorylase activity. The plasma membrane vesicles appear relatively impermeable to hypoxanthine. However, hypoxanthine, which is a competitive inhibitor of the transport reaction, is the only compound tested capable of mediating efflux of already accumulated ribose 1-PO4. In addition, hypoxanthine does not result in the efflux of transported uridine which is accumulated in these membrane vesicles as uridine. Exogenous ribose 1-PO4 neither results in counterflow nor does it inhibit the original uptake reaction. The following transport reaction is proposed: uptake occurs by group translocation, mediated by membrane-localized purine nucleoside phosphorylase. The data are consistent with sites for inosine and hypoxanthine being on the outer membrane surface whereas the ribose 1-PO4 site is only on the inner surface.", "contents": "The existance of a group translocation transport mechanism in animal cells: uptake of the ribose moiety of inosine. After exposure to inosine, transport-competent plasma membrane vesicles isolated from SV-40-transformed Bal/c 3T3 cells accumulate intravesicular ribose 1-PO4 at a concentration 200-fold greater than the extravesicular concentration. An analysis of the purine nucleoside phosphorylase activity distribution in various subcellular fractions, relative to other enzyme activities, indicated the presence of plasma membrane-associated purine nucleoside phosphorylase activity. The plasma membrane vesicles appear relatively impermeable to hypoxanthine. However, hypoxanthine, which is a competitive inhibitor of the transport reaction, is the only compound tested capable of mediating efflux of already accumulated ribose 1-PO4. In addition, hypoxanthine does not result in the efflux of transported uridine which is accumulated in these membrane vesicles as uridine. Exogenous ribose 1-PO4 neither results in counterflow nor does it inhibit the original uptake reaction. The following transport reaction is proposed: uptake occurs by group translocation, mediated by membrane-localized purine nucleoside phosphorylase. The data are consistent with sites for inosine and hypoxanthine being on the outer membrane surface whereas the ribose 1-PO4 site is only on the inner surface."} {"id": "PMID:180354", "title": "Transport of amino acids in intact 3T3 and SV3T3 cells. Binding activity for leucine in membrane preparations of ehrlich ascites tumor cells.", "content": "Transport of amino acids into 3T3 and SV3T3 (SV40 virus-transformed 3T3) cells was measured on glass cover slips. The 3T3 and SV3T3 cells contain both A (alanine preferring) and L (leucine prefferring) systems for neutral amino acid transport. Initial rates of uptake of amino acids are about twofold higher in SV3T3 than in 3T3 cells. Other parameters measured, however, do not indicate marked differences in the transport of amino acids by the two cell types. L-system amino acids, such as leucine, are subject to trans-stimulation in both cell lines, whereas A-system amino acids, such as alanine and glycine, are not. Leucine was transported to higher levels in confluent cells than in nonconfluent cells. Glycine, however, shows distinctly less transport activity as the cells become confluent. Ehrlich ascites cell plasma membranes were prepared and assayed for amino acid-binding activity. Leucine-binding activity was detected by equilibrium dialysis in Triton X-100-treated membrane preparations.", "contents": "Transport of amino acids in intact 3T3 and SV3T3 cells. Binding activity for leucine in membrane preparations of ehrlich ascites tumor cells. Transport of amino acids into 3T3 and SV3T3 (SV40 virus-transformed 3T3) cells was measured on glass cover slips. The 3T3 and SV3T3 cells contain both A (alanine preferring) and L (leucine prefferring) systems for neutral amino acid transport. Initial rates of uptake of amino acids are about twofold higher in SV3T3 than in 3T3 cells. Other parameters measured, however, do not indicate marked differences in the transport of amino acids by the two cell types. L-system amino acids, such as leucine, are subject to trans-stimulation in both cell lines, whereas A-system amino acids, such as alanine and glycine, are not. Leucine was transported to higher levels in confluent cells than in nonconfluent cells. Glycine, however, shows distinctly less transport activity as the cells become confluent. Ehrlich ascites cell plasma membranes were prepared and assayed for amino acid-binding activity. Leucine-binding activity was detected by equilibrium dialysis in Triton X-100-treated membrane preparations."} {"id": "PMID:180355", "title": "Effect of essential fatty acid deficiency on activity of liver plasma membrane enzymes in the rat.", "content": "Liver plasma membranes (LPM) were isolated from rats fed an essential fatty acid-supplemented diet (+EFA) or from rats fed an essential fatty acid-deficient diet (-EFA). The proportions of linoleate and arachidonate in membrane total fatty acids in the -EFA preparations were one-half or less than the values for the +EFA preparations. Basal, F-, or glucagon-stimulated adenylate cyclase activities were significantly lower in EFA-deficient livers than in nondeficient ones. Addition of GTP significantly enhanced glucagon-stimulated adrenylate cyclase in both groups, but extent of stimulation above basal was greater in EFA-deficient livers. Portal vein injection of glucagon in vivo resulted in significantly higher cAMP formation in +EFA livers than in -EFA livers. When glucagon was used in vitro at 1-1,000 nM, stimulation of adenylate cyclase remained lower in EFA-deficient membranes, but extent of stimulation above basal activity was larger in -EFA membranes than in +EFA. Total Na+, K+ (Mg2+)-ATPase from EFA-depleted LPM exhibited significantly higher values of apparent Km and Vmax-5'-Nucleotidase activity, in contrast, was considerably decreased in EFA-deficient rats. These findings show that, in animals, changes in unsaturated fatty acid composition can affect the properties of membrane-bound enzymes. These alterations could be due to changes in membrane physical properties and/or prostaglandin formation.", "contents": "Effect of essential fatty acid deficiency on activity of liver plasma membrane enzymes in the rat. Liver plasma membranes (LPM) were isolated from rats fed an essential fatty acid-supplemented diet (+EFA) or from rats fed an essential fatty acid-deficient diet (-EFA). The proportions of linoleate and arachidonate in membrane total fatty acids in the -EFA preparations were one-half or less than the values for the +EFA preparations. Basal, F-, or glucagon-stimulated adenylate cyclase activities were significantly lower in EFA-deficient livers than in nondeficient ones. Addition of GTP significantly enhanced glucagon-stimulated adrenylate cyclase in both groups, but extent of stimulation above basal was greater in EFA-deficient livers. Portal vein injection of glucagon in vivo resulted in significantly higher cAMP formation in +EFA livers than in -EFA livers. When glucagon was used in vitro at 1-1,000 nM, stimulation of adenylate cyclase remained lower in EFA-deficient membranes, but extent of stimulation above basal activity was larger in -EFA membranes than in +EFA. Total Na+, K+ (Mg2+)-ATPase from EFA-depleted LPM exhibited significantly higher values of apparent Km and Vmax-5'-Nucleotidase activity, in contrast, was considerably decreased in EFA-deficient rats. These findings show that, in animals, changes in unsaturated fatty acid composition can affect the properties of membrane-bound enzymes. These alterations could be due to changes in membrane physical properties and/or prostaglandin formation."} {"id": "PMID:180356", "title": "Avian tumor virus interactions with chicken fibroblast plasma membranes.", "content": "A method is described which will rapidly measure the binding of avian tumor viruses (ATV) to plasma membrane receptors. With this procedure it may be shown that Rous sarcoma virus pseudotypes bind to protease-labile, heat-stable structures on the surface of chicken embryo fibroblast (CEF) plasma membranes. The binding sites for ATV subgroups A and B appear distinct, and membranes from genetically resistant CEF bind as well those of sensitive CEF.", "contents": "Avian tumor virus interactions with chicken fibroblast plasma membranes. A method is described which will rapidly measure the binding of avian tumor viruses (ATV) to plasma membrane receptors. With this procedure it may be shown that Rous sarcoma virus pseudotypes bind to protease-labile, heat-stable structures on the surface of chicken embryo fibroblast (CEF) plasma membranes. The binding sites for ATV subgroups A and B appear distinct, and membranes from genetically resistant CEF bind as well those of sensitive CEF."} {"id": "PMID:180358", "title": "Insulinoma: clinical and diagnostic features of 60 consecutive cases.", "content": "Insulinoma is a rare tumor, occurring more often in women and in the older age range. Eighty percent of patients have a single benign tumor, usually less than or equal to 2 cm in diameter, located with about equal frequency in body, head, or tail of the pancreas and amenable to surgical cure. About 10% have multiple tumors; in this group there is a high incidence of multiple endocrine neoplasia type I syndrome. The remaining 10% of patients have metastatic malignant insulinoma. Symptoms are intermittent, recur at irregular intervals in the food-deprived state over a median of 1 1/2 years, and arise from varying degrees of neuroglycopenia. Symptoms often lead to misdiagnosis as a neurologic or psychiatric disorder. Transient neurologic deficits and EEG abnormalities can be observed during hypoglycemia. Diagnosis requires repeated demonstration of hypoglycemia (glucose less than or equal to 40 mg/dl) during spontaneous or provoked symptoms, relief with ingestion of carbohydrates, simultaneous hyperinsulinemia (serum insulin greater than 6 muU/ml), and absence of insulin antibodies. A useful diagnostic adjunct is the intravenous tolbutamide test, for which new diagnostic criteria are presented.", "contents": "Insulinoma: clinical and diagnostic features of 60 consecutive cases. Insulinoma is a rare tumor, occurring more often in women and in the older age range. Eighty percent of patients have a single benign tumor, usually less than or equal to 2 cm in diameter, located with about equal frequency in body, head, or tail of the pancreas and amenable to surgical cure. About 10% have multiple tumors; in this group there is a high incidence of multiple endocrine neoplasia type I syndrome. The remaining 10% of patients have metastatic malignant insulinoma. Symptoms are intermittent, recur at irregular intervals in the food-deprived state over a median of 1 1/2 years, and arise from varying degrees of neuroglycopenia. Symptoms often lead to misdiagnosis as a neurologic or psychiatric disorder. Transient neurologic deficits and EEG abnormalities can be observed during hypoglycemia. Diagnosis requires repeated demonstration of hypoglycemia (glucose less than or equal to 40 mg/dl) during spontaneous or provoked symptoms, relief with ingestion of carbohydrates, simultaneous hyperinsulinemia (serum insulin greater than 6 muU/ml), and absence of insulin antibodies. A useful diagnostic adjunct is the intravenous tolbutamide test, for which new diagnostic criteria are presented."} {"id": "PMID:180359", "title": "Ultrastructure of platelet aggregation in refractory anemia and myelomonocytic leukemia. II. Individual platelet abnormalities: thrombasthenia-like platelets, surface defects, and dissociation phenomena.", "content": "Studies of in vitro platelet aggregation were done in five patients with refractory anemia and two with acute myelomonocytic leukemia. The macroscopic results as well as the general ultrastructural findings were reviewed in a companion paper. Electron microscopic analysis of changes in the individual platelets within aggregates revealed a striking heterogeneity, both in the degree of response of each platelet are in the ultrastructural characteristics of the platelet population. Many of the unaggregated platelets had reacted individually, resembling the platelets of patients with Glanzmann's thrombasthenia. There were other abnormalities suggesting the presence of surface defects, such as the presence of areas of obliteration of the interplatelet space (so-called tight connections). One of the most striking findings was a peculiar dissociation between the different components of the aggregation sequence.", "contents": "Ultrastructure of platelet aggregation in refractory anemia and myelomonocytic leukemia. II. Individual platelet abnormalities: thrombasthenia-like platelets, surface defects, and dissociation phenomena. Studies of in vitro platelet aggregation were done in five patients with refractory anemia and two with acute myelomonocytic leukemia. The macroscopic results as well as the general ultrastructural findings were reviewed in a companion paper. Electron microscopic analysis of changes in the individual platelets within aggregates revealed a striking heterogeneity, both in the degree of response of each platelet are in the ultrastructural characteristics of the platelet population. Many of the unaggregated platelets had reacted individually, resembling the platelets of patients with Glanzmann's thrombasthenia. There were other abnormalities suggesting the presence of surface defects, such as the presence of areas of obliteration of the interplatelet space (so-called tight connections). One of the most striking findings was a peculiar dissociation between the different components of the aggregation sequence."} {"id": "PMID:180363", "title": "A comparison of therapeutic modalities of glomus tumors in the temporal bone.", "content": "Seventy-seven patients with glomus tumors involving the temporal bone were treated by surgery, irradiation, and combined therapy. The therapeutic success rate for the surgery group was 91 percent for glomus tympanicum and 78 percent for glomus jugulare tumors. The success rate for radiation therapy was 30% in glomus jugulare tumors. Patients with extensive lesions treated by combined therapy had a therapeutic success rate of 60 percent. The clinical response of glomus jugulare tumors to radiation therapy was 65 percent. Surgery appears to be the best method for eradication of the tumors; however, with large extensive lesions, combined therapy offers a better prognosis than either modality alone.", "contents": "A comparison of therapeutic modalities of glomus tumors in the temporal bone. Seventy-seven patients with glomus tumors involving the temporal bone were treated by surgery, irradiation, and combined therapy. The therapeutic success rate for the surgery group was 91 percent for glomus tympanicum and 78 percent for glomus jugulare tumors. The success rate for radiation therapy was 30% in glomus jugulare tumors. Patients with extensive lesions treated by combined therapy had a therapeutic success rate of 60 percent. The clinical response of glomus jugulare tumors to radiation therapy was 65 percent. Surgery appears to be the best method for eradication of the tumors; however, with large extensive lesions, combined therapy offers a better prognosis than either modality alone."} {"id": "PMID:180364", "title": "Tonsillectomy and infectious mononucleosis--a possible relationship.", "content": "A review of 1,192 student medical records shows a prior history of tonsillectomy in 41 percent of a control group and 22 percent of an infectious mononucleosis group--a significant difference (p less than 0.01). Nine hundred eighty-nine Stanford University students (421 females, 568 males) who visited Cowell Student Health Center between April and September, 1973, comprise the control group. Two hundred three students with positive monospot tests and clinical mononucleosis diagnosed between June, 1968, and May, 1973, comprise the experimental group. The lower incidence of tonsillectomy in the infectious mononucleosis group implies that the tonsillar lymphoid tissue serves as a reservoir and possible replicating milieu for the Epstein-Barr virus. Prior tonsillectomy may reduce the possibility of contracting infectious mononucleosis.", "contents": "Tonsillectomy and infectious mononucleosis--a possible relationship. A review of 1,192 student medical records shows a prior history of tonsillectomy in 41 percent of a control group and 22 percent of an infectious mononucleosis group--a significant difference (p less than 0.01). Nine hundred eighty-nine Stanford University students (421 females, 568 males) who visited Cowell Student Health Center between April and September, 1973, comprise the control group. Two hundred three students with positive monospot tests and clinical mononucleosis diagnosed between June, 1968, and May, 1973, comprise the experimental group. The lower incidence of tonsillectomy in the infectious mononucleosis group implies that the tonsillar lymphoid tissue serves as a reservoir and possible replicating milieu for the Epstein-Barr virus. Prior tonsillectomy may reduce the possibility of contracting infectious mononucleosis."} {"id": "PMID:180360", "title": "Effects of electrical stimulation and norepinephrine on cyclic-AMP levels in the cerebral cortex of the aging rat.", "content": "One to 24 month old rats were anesthetized with alpha-chloralose, their cerebral cortices exposed surgically and subjected in vivo to stimulation by norepinephrine (1.0mM for 5 minutes) or electrical pulses (100 pulses/s for 10 s). After microwave fixation, cortical samples were analyzed for cyclic-AMP by the Gilman method. In similarly prepared but unstimulated control animals, cyclic-AMP levels were found to be three to four-fold lower in older than in younger rats, a pattern previously reported for unanesthetized rats. Both norepinephrine and electrical pulses led to cyclic AMP increases. With increasing age the cyclic-AMP levels attained under both stimulus conditions declined, with the levels achieved in the two cases becoming increasingly divergent.", "contents": "Effects of electrical stimulation and norepinephrine on cyclic-AMP levels in the cerebral cortex of the aging rat. One to 24 month old rats were anesthetized with alpha-chloralose, their cerebral cortices exposed surgically and subjected in vivo to stimulation by norepinephrine (1.0mM for 5 minutes) or electrical pulses (100 pulses/s for 10 s). After microwave fixation, cortical samples were analyzed for cyclic-AMP by the Gilman method. In similarly prepared but unstimulated control animals, cyclic-AMP levels were found to be three to four-fold lower in older than in younger rats, a pattern previously reported for unanesthetized rats. Both norepinephrine and electrical pulses led to cyclic AMP increases. With increasing age the cyclic-AMP levels attained under both stimulus conditions declined, with the levels achieved in the two cases becoming increasingly divergent."} {"id": "PMID:180361", "title": "A morphometric and cytochemical analysis of aging changes in the flight muscle of Nasonia vitripennis (Walk) (Hymenoptera, pteromalidae).", "content": "A morphometric and cytochemical analysis was carried out on the effect of age and diet on the flight muscles of Nasonia vitripennis (Walk). A significant decline in mitochondrial volume with age is revealed in pupae-fed insects, but this is not recorded in sucrose-fed insects. There is also a significant decline in the activity of cytochrome oxidase in sucrose-fed, but not in pupae-fed, insects. It is concluded that the sucrose diet caused a delay in the ultrastructural deterioration of the flight muscles.", "contents": "A morphometric and cytochemical analysis of aging changes in the flight muscle of Nasonia vitripennis (Walk) (Hymenoptera, pteromalidae). A morphometric and cytochemical analysis was carried out on the effect of age and diet on the flight muscles of Nasonia vitripennis (Walk). A significant decline in mitochondrial volume with age is revealed in pupae-fed insects, but this is not recorded in sucrose-fed insects. There is also a significant decline in the activity of cytochrome oxidase in sucrose-fed, but not in pupae-fed, insects. It is concluded that the sucrose diet caused a delay in the ultrastructural deterioration of the flight muscles."} {"id": "PMID:180365", "title": "[Current concepts of intestinal fat absorption(author's transl)].", "content": "Some details of the general physiology of intestinal fat absorption are discussed taking triglyceride absorption as an example. Special emphasis is placed upon the role of the fatty acid binding protein (FABP) just recently discovered and upon the role of apoproteins for lipid transport from the epithelial cells to the intestinal lymph. On basis of own experimental results the hypothesis is put forward, that a small part of the intestinal energy requirement during fat absorption may be provided by intestinal oxydation of plasma free fatty acids.", "contents": "[Current concepts of intestinal fat absorption(author's transl)]. Some details of the general physiology of intestinal fat absorption are discussed taking triglyceride absorption as an example. Special emphasis is placed upon the role of the fatty acid binding protein (FABP) just recently discovered and upon the role of apoproteins for lipid transport from the epithelial cells to the intestinal lymph. On basis of own experimental results the hypothesis is put forward, that a small part of the intestinal energy requirement during fat absorption may be provided by intestinal oxydation of plasma free fatty acids."} {"id": "PMID:180373", "title": "Effect of alimentation on human serum squalene levels.", "content": "Five subjects consumed a meal containing ca. 1.5 mg squalene. Postprandial serum samples showed that in three of the subjects squalene and lipid levels reached maxima at 3 hr. Squalene levels in the low density lipoproteins of these subjects also increased. The results indicate that alimentation is a major factor in the variation in serum squalene levels.", "contents": "Effect of alimentation on human serum squalene levels. Five subjects consumed a meal containing ca. 1.5 mg squalene. Postprandial serum samples showed that in three of the subjects squalene and lipid levels reached maxima at 3 hr. Squalene levels in the low density lipoproteins of these subjects also increased. The results indicate that alimentation is a major factor in the variation in serum squalene levels."} {"id": "PMID:180383", "title": "[Oxidative phosphorylation capacity of Rhodopseudomonas palustris during growth in light and darkness].", "content": "Assimilation of oxygen by the cells of Rhodopseudomonas palustris grown in the light and in the darkness is stimulated by p-chlorocarbonylcyanidephanylhydrazone, suggesting respiration coupled to phosphorylatin. Membranes of the cells grown in the light are capable of oxidative phosphorylation in the course of electron transport from NADH and succinate to O2 with P/O being 0.03 and 0.20, respectively. Membranes of the cells grown in the darkness in aerobic conditions are capable of oxidative phosphorylation in the presence of NADH, succinate and ascorbate + phenazinemetasulphate with P/O being 0.25, 0.40 and 0.06, respectively. Phosphorylation during oxidation of ascorbate + phenazinemetasulphate in the cells grown in the darkness suggests that the third point of coupling has appeared as a result of synthesis of cytochrome a. There are only minor differences in phosphorylation in the membranes of the cells grown in the light and in the darkness, as was shown by its susceptibility to p-chlorocarbonylcyanidephenyl-hydrazone, oligomycin, antimycin A and cyanide.", "contents": "[Oxidative phosphorylation capacity of Rhodopseudomonas palustris during growth in light and darkness]. Assimilation of oxygen by the cells of Rhodopseudomonas palustris grown in the light and in the darkness is stimulated by p-chlorocarbonylcyanidephanylhydrazone, suggesting respiration coupled to phosphorylatin. Membranes of the cells grown in the light are capable of oxidative phosphorylation in the course of electron transport from NADH and succinate to O2 with P/O being 0.03 and 0.20, respectively. Membranes of the cells grown in the darkness in aerobic conditions are capable of oxidative phosphorylation in the presence of NADH, succinate and ascorbate + phenazinemetasulphate with P/O being 0.25, 0.40 and 0.06, respectively. Phosphorylation during oxidation of ascorbate + phenazinemetasulphate in the cells grown in the darkness suggests that the third point of coupling has appeared as a result of synthesis of cytochrome a. There are only minor differences in phosphorylation in the membranes of the cells grown in the light and in the darkness, as was shown by its susceptibility to p-chlorocarbonylcyanidephenyl-hydrazone, oligomycin, antimycin A and cyanide."} {"id": "PMID:180385", "title": "[Inhibitory analysis of the respiration of bacteroids from the nodules of yellow lupine].", "content": "Oxygen uptake and reduction of C2H2 by bacteroids was found to be inhibited by low concentrations of cyanide and azide. However, oxygen uptake was not completely suppressed even by 10(-3) M KCN. Cyanide-resistant respiration was not inhibited by salicyl-hydroxamic acid, and seemed to be accomplished at the account of autoxidable flavo-proteins. A small light-reversible inhibition of respiration by carbon monoxide was found only in the bacteroids with a high rate of nitrogen fixation. Rotenone, antimycin A, and tenoyltrifluoroacetone inhibited oxygen uptake and methylene reduction. Nitrogen fixation, but not respiration, was inhibited by 2,4-dinitrophenol. An electron-transport chain coupled with phosphorylation is supposed to be built into the membranes of the bacteroids. The activity of peroxidase and cytochrome peroxidase was demonstrated in the bacteroids.", "contents": "[Inhibitory analysis of the respiration of bacteroids from the nodules of yellow lupine]. Oxygen uptake and reduction of C2H2 by bacteroids was found to be inhibited by low concentrations of cyanide and azide. However, oxygen uptake was not completely suppressed even by 10(-3) M KCN. Cyanide-resistant respiration was not inhibited by salicyl-hydroxamic acid, and seemed to be accomplished at the account of autoxidable flavo-proteins. A small light-reversible inhibition of respiration by carbon monoxide was found only in the bacteroids with a high rate of nitrogen fixation. Rotenone, antimycin A, and tenoyltrifluoroacetone inhibited oxygen uptake and methylene reduction. Nitrogen fixation, but not respiration, was inhibited by 2,4-dinitrophenol. An electron-transport chain coupled with phosphorylation is supposed to be built into the membranes of the bacteroids. The activity of peroxidase and cytochrome peroxidase was demonstrated in the bacteroids."} {"id": "PMID:180393", "title": "Clinical studies of 5-fluorouracil + premarin in the treatment of breast cancer.", "content": "Sixty patients with metastatic or primary inoperable breast cancer not suitable for hormone alteration therapy were blindly randomized between weekly 5-fluorouracil, intravenously, and daily physiologic doses of conjugated estrogens by mouth against weekly 5-fluorouracil, intravenously, and placebo. There was no difference in the survival or the effect on the tumor in the two groups. Numerous factors were analyzed as to their effect on the course of the disease. The number of organ sites of tumor involvement, age of the host, and previous treatment for the disseminated disease were not shown to influence the survival or the results of therapy of either group. However, the duration of the clinical cancer-free period from primary treatment to recurrence, the sites of organ involvement, and the performance status of the patients at the time of entry into the study significantly did influence the survival. There is no evidence in this study that physiologic doses of conjugated estrogens deleteriously influenced the course of the disease.", "contents": "Clinical studies of 5-fluorouracil + premarin in the treatment of breast cancer. Sixty patients with metastatic or primary inoperable breast cancer not suitable for hormone alteration therapy were blindly randomized between weekly 5-fluorouracil, intravenously, and daily physiologic doses of conjugated estrogens by mouth against weekly 5-fluorouracil, intravenously, and placebo. There was no difference in the survival or the effect on the tumor in the two groups. Numerous factors were analyzed as to their effect on the course of the disease. The number of organ sites of tumor involvement, age of the host, and previous treatment for the disseminated disease were not shown to influence the survival or the results of therapy of either group. However, the duration of the clinical cancer-free period from primary treatment to recurrence, the sites of organ involvement, and the performance status of the patients at the time of entry into the study significantly did influence the survival. There is no evidence in this study that physiologic doses of conjugated estrogens deleteriously influenced the course of the disease."} {"id": "PMID:180387", "title": "[Polyphosphate biosynthesis in Rhodospirillum rubrum chromatophores].", "content": "The chromatophores of Rhodospirillum rubrum were found to synthesize in the light not only ATP and pyrophosphate but also high molecular weight polyphosphates. Biosynthesis of all studied compounds was inhibited by antimycin A, an inhibitor of the electron-transport photosynthetic chain. Synthesis of high molecular weight polyphosphates is stimulated, while that of pyrophosphate is inhibited, in the conditions providing intensive synthesis of ATP (in the presence of ADP and in the absence of oligomycin). The results obtained suggest that biosynthesis of high molecular weight polyphosphates is related to photosynthetic phosphorylation, via ATP but not pyrophosphate.", "contents": "[Polyphosphate biosynthesis in Rhodospirillum rubrum chromatophores]. The chromatophores of Rhodospirillum rubrum were found to synthesize in the light not only ATP and pyrophosphate but also high molecular weight polyphosphates. Biosynthesis of all studied compounds was inhibited by antimycin A, an inhibitor of the electron-transport photosynthetic chain. Synthesis of high molecular weight polyphosphates is stimulated, while that of pyrophosphate is inhibited, in the conditions providing intensive synthesis of ATP (in the presence of ADP and in the absence of oligomycin). The results obtained suggest that biosynthesis of high molecular weight polyphosphates is related to photosynthetic phosphorylation, via ATP but not pyrophosphate."} {"id": "PMID:180399", "title": "[A study of the Brownian movement of alpha-chymotrypsin molecules by the spin probe method].", "content": "The rotation of alpha-chymotripsin in water solution is studied by use of nitroxyl radical, which is adsorbed by the alpha-chymotrypsin. It has been shown that under the conditions used the probe is fixed on the rotating diffusive protein monomer. Theoretical calculations of possible rotation correlation times for alpha-chymotripsin molecule were performed taking into account hydration and non-spherical shape. Experimental data obtained are in good agreement with theoretical values.", "contents": "[A study of the Brownian movement of alpha-chymotrypsin molecules by the spin probe method]. The rotation of alpha-chymotripsin in water solution is studied by use of nitroxyl radical, which is adsorbed by the alpha-chymotrypsin. It has been shown that under the conditions used the probe is fixed on the rotating diffusive protein monomer. Theoretical calculations of possible rotation correlation times for alpha-chymotripsin molecule were performed taking into account hydration and non-spherical shape. Experimental data obtained are in good agreement with theoretical values."} {"id": "PMID:180400", "title": "[Formation of a complex between carbon monoxide and cytochrome C].", "content": "The conditions of structural modifications of horse heart cytochrome c (pH, salt concentration) have been studied. Under these conditions the rate of carboxycytochrome c formation greatly increases in the course of the reduction process as compared to this rate after cytochrome c reduction and relaxation to the equilibrium state. According to these results the reduced intermediate which appears in the course of reduction has a high affinity for the carbon monoxide. It has been shown that the reduced low-spin cytochrome c practically does not take part in the process of dynamic conformational equilibrium with other cytochrome c forms existing in equilibrium mixture of oxidized and reduced cytochrome c.", "contents": "[Formation of a complex between carbon monoxide and cytochrome C]. The conditions of structural modifications of horse heart cytochrome c (pH, salt concentration) have been studied. Under these conditions the rate of carboxycytochrome c formation greatly increases in the course of the reduction process as compared to this rate after cytochrome c reduction and relaxation to the equilibrium state. According to these results the reduced intermediate which appears in the course of reduction has a high affinity for the carbon monoxide. It has been shown that the reduced low-spin cytochrome c practically does not take part in the process of dynamic conformational equilibrium with other cytochrome c forms existing in equilibrium mixture of oxidized and reduced cytochrome c."} {"id": "PMID:180405", "title": "[The combined treatment of bronchial carcinoma (author's transl)].", "content": "A preliminary assessment of a chemotherapeutic study is presented. The polychemotherapy was given as a high dosage intermittent stosstherapy with 3 infusions at intervals of a week for 3 years. The group of randomized controls included 126 patients who were classified according to the stage classification of the TNM system and Feinstein's system, which takes into account the clinical symptoms. Comparison of the death rates with the controls shows a distinct advantage in favor of the patients treated chemotherapeutically in all TNM classes.", "contents": "[The combined treatment of bronchial carcinoma (author's transl)]. A preliminary assessment of a chemotherapeutic study is presented. The polychemotherapy was given as a high dosage intermittent stosstherapy with 3 infusions at intervals of a week for 3 years. The group of randomized controls included 126 patients who were classified according to the stage classification of the TNM system and Feinstein's system, which takes into account the clinical symptoms. Comparison of the death rates with the controls shows a distinct advantage in favor of the patients treated chemotherapeutically in all TNM classes."} {"id": "PMID:180406", "title": "[Congenital enzyme deficiency in carbohydrate metabolism. Its significance for clinical pediatrics and human biochemical genetics (author's transl)].", "content": "A review of the enzyme deficiencies of carbohydrate metabolism known at the present time is given. Through prominent clinical symptoms and consideration of food as a pathological agent, it is possible to suspect the various diseases before the results of the biochemical determinations are available. On account of the sometimes striking course, therapy can consequently be started at the earliest possible moment.", "contents": "[Congenital enzyme deficiency in carbohydrate metabolism. Its significance for clinical pediatrics and human biochemical genetics (author's transl)]. A review of the enzyme deficiencies of carbohydrate metabolism known at the present time is given. Through prominent clinical symptoms and consideration of food as a pathological agent, it is possible to suspect the various diseases before the results of the biochemical determinations are available. On account of the sometimes striking course, therapy can consequently be started at the earliest possible moment."} {"id": "PMID:180408", "title": "Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin.", "content": "To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors.", "contents": "Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin. To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors."} {"id": "PMID:180409", "title": "Menopausal estrogens and breast cancer.", "content": "1891 women given conjugated estrogens for the menopause were followed for 12 years (mean) for incidence of breast cancer. Overall, 49 cases were observed; 39.1 were expected on the basis of rates in the general population (relative risk = 1.3, P = 0.06). The relative risk increased with follow-up duration, progressing to 2.0 after 15 years (13/6.6, P = 0.01). The excess risk after 10 years was not due simply to prolonged estrogen use, since there was no clear dose-response relation to accumulated years of use. However, higher risk accrued to women using higher-dose tablets and those taking the medication on an other than daily basis. In addition, after 10 years of follow-up observation, two factors related to low risk of breast cancer, multiparity and oophorectomy, were no longer so related. Finally, estrogen use was related to an especially high risk of breast cancer among women in whom benign disease developed after they had started the drug.", "contents": "Menopausal estrogens and breast cancer. 1891 women given conjugated estrogens for the menopause were followed for 12 years (mean) for incidence of breast cancer. Overall, 49 cases were observed; 39.1 were expected on the basis of rates in the general population (relative risk = 1.3, P = 0.06). The relative risk increased with follow-up duration, progressing to 2.0 after 15 years (13/6.6, P = 0.01). The excess risk after 10 years was not due simply to prolonged estrogen use, since there was no clear dose-response relation to accumulated years of use. However, higher risk accrued to women using higher-dose tablets and those taking the medication on an other than daily basis. In addition, after 10 years of follow-up observation, two factors related to low risk of breast cancer, multiparity and oophorectomy, were no longer so related. Finally, estrogen use was related to an especially high risk of breast cancer among women in whom benign disease developed after they had started the drug."} {"id": "PMID:180425", "title": "Translation in vitro of vesicular stomatitis virus mRNA lacking 5'-terminal 7-methylguanosine.", "content": "The 5'-terminus 7-methylguanosine of vesicular stomatitis virus mRNA is not essential for translation of the mRNA. The 7-methylguanosine seems to have a mediating rather than an obligatory role in ribosome binding by the mRNA and in mRNA translation.", "contents": "Translation in vitro of vesicular stomatitis virus mRNA lacking 5'-terminal 7-methylguanosine. The 5'-terminus 7-methylguanosine of vesicular stomatitis virus mRNA is not essential for translation of the mRNA. The 7-methylguanosine seems to have a mediating rather than an obligatory role in ribosome binding by the mRNA and in mRNA translation."} {"id": "PMID:180430", "title": "Relationship between receptor and mammary tumour virus production after stimulation by glucocorticoid.", "content": "A short exposure of primary cultures of mouse mammary tumour cells to glucocorticoids results in at least a three-fold stimulation of mammary tumour virus (MTV) production. Specific interaction of glucocorticoids with the cytoplasmic and nuclear receptors can also be demonstrated. The biological potency of various steroids to stimulate MTV is related directly to the retention of the steroid-receptor complex in the nuclei. Progesterone has a high affinity for the cytoplasmic receptor, is not retained by the nuclei and does not stimulate or block the basal level of MTV production. It is, however, quite effective in abolishing the glucocorticoid-mediated stimulation of MTV and thus behaves as an antagonist of glucocorticoid.", "contents": "Relationship between receptor and mammary tumour virus production after stimulation by glucocorticoid. A short exposure of primary cultures of mouse mammary tumour cells to glucocorticoids results in at least a three-fold stimulation of mammary tumour virus (MTV) production. Specific interaction of glucocorticoids with the cytoplasmic and nuclear receptors can also be demonstrated. The biological potency of various steroids to stimulate MTV is related directly to the retention of the steroid-receptor complex in the nuclei. Progesterone has a high affinity for the cytoplasmic receptor, is not retained by the nuclei and does not stimulate or block the basal level of MTV production. It is, however, quite effective in abolishing the glucocorticoid-mediated stimulation of MTV and thus behaves as an antagonist of glucocorticoid."} {"id": "PMID:180433", "title": "Initiation sites of Rous sarcoma virus RNA-directed DNA synthesis in vitro.", "content": "Rous sarcoma virus DNA synthesis in disrupted virions is initiated mainly at a site about 200 nucleotides or less from the 5' terminus, but other initiation sites throughtout the RNA seem to be used as well. No AUG triplet occurs within a 5' terminal segment of about 25 nucleotides.", "contents": "Initiation sites of Rous sarcoma virus RNA-directed DNA synthesis in vitro. Rous sarcoma virus DNA synthesis in disrupted virions is initiated mainly at a site about 200 nucleotides or less from the 5' terminus, but other initiation sites throughtout the RNA seem to be used as well. No AUG triplet occurs within a 5' terminal segment of about 25 nucleotides."} {"id": "PMID:180434", "title": "Proviral sequences of baboon endogenous type C RNA virus in DNA of human leukaemic tissues.", "content": "Hybridisation of RNA from a baboon endogenous type C RNA virus to DNA from tissues of leukaemic patients indicates that a virus of this type is horizontally transmitted among humans. DNA from several patients with leukaemia hybridised 70% of the hybridisable RNA from baboon endogenous type C RNA virus (BaEV) and yielded hybrids of high tm, whereas DNA from normal human tissues hybridised only 23% of the BaEV RNA, and the tm of these hybrids was lower.", "contents": "Proviral sequences of baboon endogenous type C RNA virus in DNA of human leukaemic tissues. Hybridisation of RNA from a baboon endogenous type C RNA virus to DNA from tissues of leukaemic patients indicates that a virus of this type is horizontally transmitted among humans. DNA from several patients with leukaemia hybridised 70% of the hybridisable RNA from baboon endogenous type C RNA virus (BaEV) and yielded hybrids of high tm, whereas DNA from normal human tissues hybridised only 23% of the BaEV RNA, and the tm of these hybrids was lower."} {"id": "PMID:180440", "title": "Stepwise transition of aggregate structure of high-molecular-weight avian myeloblastosis virus RNA. Mode of releasing of associated 4S RNA.", "content": "Mode of releasing of associated 4S RNA species was studied during a controlled transition of aggregate structure of high-molecular-weight AMV-RNA. It has been found that associated 4S RNA constitutes 2.5% of 60S AMV-RNA complex. Approximately 60% of associated 4S RNA is successively released during treatment of viral RNA with increasing formamide concentration, concomitantly with the transition of 60S RNA aggregate through 50--55S RNA intermediate into the final 30--40S RNA subunits. 40% of 4S RNA remains associated with 30--40S RNA subunits prepared by formamide treatment and can be released from them by heating. A procedure is thus provided both for the isolation of oncornaviral RNA subunit structures deprived of various partions of associated 4S RNA and for the fractionation of 4S RNA species according to their binding affinity to the genome oncornaviral RNA.", "contents": "Stepwise transition of aggregate structure of high-molecular-weight avian myeloblastosis virus RNA. Mode of releasing of associated 4S RNA. Mode of releasing of associated 4S RNA species was studied during a controlled transition of aggregate structure of high-molecular-weight AMV-RNA. It has been found that associated 4S RNA constitutes 2.5% of 60S AMV-RNA complex. Approximately 60% of associated 4S RNA is successively released during treatment of viral RNA with increasing formamide concentration, concomitantly with the transition of 60S RNA aggregate through 50--55S RNA intermediate into the final 30--40S RNA subunits. 40% of 4S RNA remains associated with 30--40S RNA subunits prepared by formamide treatment and can be released from them by heating. A procedure is thus provided both for the isolation of oncornaviral RNA subunit structures deprived of various partions of associated 4S RNA and for the fractionation of 4S RNA species according to their binding affinity to the genome oncornaviral RNA."} {"id": "PMID:180441", "title": "Influence of BCG vaccination on the primary and transplantable hamster tumors induced by SV40 and on the specific SV40 virus-induced antitumor immunity.", "content": "The main purpose of the study was the estimation of the effect of BCG vaccination and BCG in the combination with the specific immunization with SV40 on the incidence of primary and growth of transplantable SV40-induced tumors in Syrian hamsters. Different BCG vaccine preparations containing 60--100 millions of viable Mycobacteries per 1 mg were used. It has been demonstrated that one and two intradermal injections of BCG (0.25 mg per animal) during the latent period in Syrian hamsters inoculated with SV40 when newborn had no influence on the incidence of primary SV40-induced tumors. Repeated six injections of BCG during the latent period increased the frequency of tumors in one of two experiments. The subsequent was concern with investigation of the effect of BCG vaccination and its different combinations with specific immunization with SV40 on the growth of transplantable SV40-induced tumors in adult Syrian hamsters. Experimental data have shown that different preparations of BCG were varying in the capacity to increase nonspecific antitumor resistance; some preparations were nonimmunogeneic. Injections of a mixture of BCG and SV40 as well as BCG followed with SV40 14 and 20 days later did not lead to summation of effects of immunization, even when immunogenic preparations of BCG were used. Moreover inoculation of SV40 followed with BCG injection 4, 14 or 20 days later completely or partly declined the effect of SV40 specific immunization. Possible mechanisms of the negative effect of BCG on specific antitumor resistance are discussed.", "contents": "Influence of BCG vaccination on the primary and transplantable hamster tumors induced by SV40 and on the specific SV40 virus-induced antitumor immunity. The main purpose of the study was the estimation of the effect of BCG vaccination and BCG in the combination with the specific immunization with SV40 on the incidence of primary and growth of transplantable SV40-induced tumors in Syrian hamsters. Different BCG vaccine preparations containing 60--100 millions of viable Mycobacteries per 1 mg were used. It has been demonstrated that one and two intradermal injections of BCG (0.25 mg per animal) during the latent period in Syrian hamsters inoculated with SV40 when newborn had no influence on the incidence of primary SV40-induced tumors. Repeated six injections of BCG during the latent period increased the frequency of tumors in one of two experiments. The subsequent was concern with investigation of the effect of BCG vaccination and its different combinations with specific immunization with SV40 on the growth of transplantable SV40-induced tumors in adult Syrian hamsters. Experimental data have shown that different preparations of BCG were varying in the capacity to increase nonspecific antitumor resistance; some preparations were nonimmunogeneic. Injections of a mixture of BCG and SV40 as well as BCG followed with SV40 14 and 20 days later did not lead to summation of effects of immunization, even when immunogenic preparations of BCG were used. Moreover inoculation of SV40 followed with BCG injection 4, 14 or 20 days later completely or partly declined the effect of SV40 specific immunization. Possible mechanisms of the negative effect of BCG on specific antitumor resistance are discussed."} {"id": "PMID:180442", "title": "Effect of nucleosides on the synthesis of nucleic acids and proteins in Ehrlich ascites carcinoma cells.", "content": "The synthesis of nucleic acids and proteins in whole cells of Ehrlich ascites carcinoma was inhibited by adenosine and by several natural-adenosine-related compounds. The inhibitory effect of adenosine was more pronounced than that of other nucleosides tested (guanosine, inosine, cytidine, uridine and thymidine). The synthetic processes examined were only moderately inhibited by adenine nucleotides (ATP, ADP, AMP, NAD, cyclic 3',5'-AMP and its dibutyryl derivative). Respiration and aerobic glycolysis were not affected significantly by the nucleoside tested.", "contents": "Effect of nucleosides on the synthesis of nucleic acids and proteins in Ehrlich ascites carcinoma cells. The synthesis of nucleic acids and proteins in whole cells of Ehrlich ascites carcinoma was inhibited by adenosine and by several natural-adenosine-related compounds. The inhibitory effect of adenosine was more pronounced than that of other nucleosides tested (guanosine, inosine, cytidine, uridine and thymidine). The synthetic processes examined were only moderately inhibited by adenine nucleotides (ATP, ADP, AMP, NAD, cyclic 3',5'-AMP and its dibutyryl derivative). Respiration and aerobic glycolysis were not affected significantly by the nucleoside tested."} {"id": "PMID:180443", "title": "Induction of estrous cycles in old non-cyclic rats by progesterone, ACTH, ether stress or L-dopa.", "content": "Cycling was induced in old non-cyclic, constant estrous rats by daily injections of progesterone, ACTH or L-dopa or by subjection to ether stress. Progesterone and ACTH were the most effective agents used for re-establishing estrous cycles in these rats. Most of the progesterone- and ACTH-treated rats showed regular cycles, and their ovaries had many corpora lutea; they also showed proestrous serum LH surges. Ether stress and L-dopa mostly induced irregular cycles and fewer corpora lutea in the ovaries; a smaller number of these rats showed proestrous LH surges. After treatment with each of these agents was discontinued, most of the rats returned to constant estrus or irregular cycling.", "contents": "Induction of estrous cycles in old non-cyclic rats by progesterone, ACTH, ether stress or L-dopa. Cycling was induced in old non-cyclic, constant estrous rats by daily injections of progesterone, ACTH or L-dopa or by subjection to ether stress. Progesterone and ACTH were the most effective agents used for re-establishing estrous cycles in these rats. Most of the progesterone- and ACTH-treated rats showed regular cycles, and their ovaries had many corpora lutea; they also showed proestrous serum LH surges. Ether stress and L-dopa mostly induced irregular cycles and fewer corpora lutea in the ovaries; a smaller number of these rats showed proestrous LH surges. After treatment with each of these agents was discontinued, most of the rats returned to constant estrus or irregular cycling."} {"id": "PMID:180444", "title": "Dissociation between LH release and pituitary cyclic nucleotide accumulation in response to synthetic LH-releasing hormone in vivo.", "content": "In order to clarify the role of cyclic nucleotides in the mediation of LH-releasing hormone (LH-RH) action on LH release, the effect of LH-RH on LH release and pituitary cyclic AMP and cyclic GMP accumulation was studied in vivo. Pituitary cyclic AMP levels were increased 10 min after the intraveneous injection of 2 mg dibutyryl cyclic AMP (db-cyclic AMP) or 25 mg aminophylline. However, serum LH levels were not altered at 10, 30 or 60 min after the administration of either agent. Synthetic LH-RH (100 ng/rat) increased serum LH levels as measured 10 min after injection, but no effect on either pituitary cyclic AMP or cyclic GMP was seen 1, 5 or 10 min after LH-RH administration. These in vivo results are contradictory to the second messenger hypothesis for either cyclic AMP or cyclic GMP in the mediation of LH-RH-induced LH released and suggest that further work must be done in order to confirm or reject this hypothesis.", "contents": "Dissociation between LH release and pituitary cyclic nucleotide accumulation in response to synthetic LH-releasing hormone in vivo. In order to clarify the role of cyclic nucleotides in the mediation of LH-releasing hormone (LH-RH) action on LH release, the effect of LH-RH on LH release and pituitary cyclic AMP and cyclic GMP accumulation was studied in vivo. Pituitary cyclic AMP levels were increased 10 min after the intraveneous injection of 2 mg dibutyryl cyclic AMP (db-cyclic AMP) or 25 mg aminophylline. However, serum LH levels were not altered at 10, 30 or 60 min after the administration of either agent. Synthetic LH-RH (100 ng/rat) increased serum LH levels as measured 10 min after injection, but no effect on either pituitary cyclic AMP or cyclic GMP was seen 1, 5 or 10 min after LH-RH administration. These in vivo results are contradictory to the second messenger hypothesis for either cyclic AMP or cyclic GMP in the mediation of LH-RH-induced LH released and suggest that further work must be done in order to confirm or reject this hypothesis."} {"id": "PMID:180445", "title": "Effects of drugs that modify brain biogenic amine concentrations on thyroid activation induced by exposure to cold.", "content": "L-Dihydroxphenylalanine (L-DOPA) significantly inhibited intrathyroidal colloid droplet formation induced by exposure to cold in the rat. Diethyldithiocarbamate (DDC) also inhibited colloid droplet formation in response to cold. The combined administration of L-DOPA and DDC produced an additive inhibition of the thyroidal endocytotic response to exposure to cold. Pretreatment with chlorpromazine (CPZ) ameliorated the inhibitory effect of L-DOPA. DL-alpha-methyl-p-tyrosine (alpha-MT) also signficantly depressed the thyroidal response. Inhibition of colloid droplet formation induced by alpha-MT was not altered by the administration of DL-dihydroxyphenylserine (DL-DOPS). On the other hand, treatment of the alpha-MT-treated rats with L-DOPA to normalize dopamine synthesis resulted in a dramatic recovery from the inhibition. Blockade of serotonin biosynthesis with p-chlorophenylalanine (p-CPA) failed to produce a significant inhibition of colloid droplet formation. However, 5-hydroxytryptophan (5-HTP) markedly inhibited the thyroidal response to cold. Brocresine phosphate (BP) was another inhibitor of the thyroidal endocytotic response to exposure to cold. Oxotremorine also markedly depressed the thyroidal response to cold. Since these drugs did not interfere with pituitary thyroid responsiveness to exogenous thyrotropin-releasing hormone (TRH), it seems that the throidal endocytotic response to exposure to cold as a reflection of TSH secretion was directly influenced by alterations of brain biogenic amine concentrations or turnover rates.", "contents": "Effects of drugs that modify brain biogenic amine concentrations on thyroid activation induced by exposure to cold. L-Dihydroxphenylalanine (L-DOPA) significantly inhibited intrathyroidal colloid droplet formation induced by exposure to cold in the rat. Diethyldithiocarbamate (DDC) also inhibited colloid droplet formation in response to cold. The combined administration of L-DOPA and DDC produced an additive inhibition of the thyroidal endocytotic response to exposure to cold. Pretreatment with chlorpromazine (CPZ) ameliorated the inhibitory effect of L-DOPA. DL-alpha-methyl-p-tyrosine (alpha-MT) also signficantly depressed the thyroidal response. Inhibition of colloid droplet formation induced by alpha-MT was not altered by the administration of DL-dihydroxyphenylserine (DL-DOPS). On the other hand, treatment of the alpha-MT-treated rats with L-DOPA to normalize dopamine synthesis resulted in a dramatic recovery from the inhibition. Blockade of serotonin biosynthesis with p-chlorophenylalanine (p-CPA) failed to produce a significant inhibition of colloid droplet formation. However, 5-hydroxytryptophan (5-HTP) markedly inhibited the thyroidal response to cold. Brocresine phosphate (BP) was another inhibitor of the thyroidal endocytotic response to exposure to cold. Oxotremorine also markedly depressed the thyroidal response to cold. Since these drugs did not interfere with pituitary thyroid responsiveness to exogenous thyrotropin-releasing hormone (TRH), it seems that the throidal endocytotic response to exposure to cold as a reflection of TSH secretion was directly influenced by alterations of brain biogenic amine concentrations or turnover rates."} {"id": "PMID:180446", "title": "In vitro release of ACTH from dispersed rat pars intermedia cells. I. Effect of secretagogues.", "content": "Studies were made to test the responsiveness of dispersed pars intermedia (PI) cells to a number of secretagogues, that are known to alter ACTH release from the pars distalis (PD) in vitro. In summary, (a) incubation in high (K+), which will increase ACTH release from the PD, did not alter ACTH release from the PI; (b) a crude extract of rat hypothalamus (HE) increased ACTH release from PD and PI; (c) the effect of HE was not due to its vasopression content, since pretreatment of the extract with thioglycolic acid did not modify its ACTH-releasing activity and neither lysine nor arginine vasopressin stimulated ACTH release from the PI; and (d) a partially purified CRF preparation, which will stimulate ACTH release from the PD, did not alter ACTH release from the PI. We conclude that the hypothalamus contains a substance(s) that will stimulate ACTH release from the PI and that the 'secretagogue' is neither vasopressin nor the same CRF that will stimulate ACTH release from the PD.", "contents": "In vitro release of ACTH from dispersed rat pars intermedia cells. I. Effect of secretagogues. Studies were made to test the responsiveness of dispersed pars intermedia (PI) cells to a number of secretagogues, that are known to alter ACTH release from the pars distalis (PD) in vitro. In summary, (a) incubation in high (K+), which will increase ACTH release from the PD, did not alter ACTH release from the PI; (b) a crude extract of rat hypothalamus (HE) increased ACTH release from PD and PI; (c) the effect of HE was not due to its vasopression content, since pretreatment of the extract with thioglycolic acid did not modify its ACTH-releasing activity and neither lysine nor arginine vasopressin stimulated ACTH release from the PI; and (d) a partially purified CRF preparation, which will stimulate ACTH release from the PD, did not alter ACTH release from the PI. We conclude that the hypothalamus contains a substance(s) that will stimulate ACTH release from the PI and that the 'secretagogue' is neither vasopressin nor the same CRF that will stimulate ACTH release from the PD."} {"id": "PMID:180452", "title": "Effect of corticosteroids on the phrenic nerve-diaphragm of preparation treated with hemicholinium. A possible model of myasthenia gravis.", "content": "A marked protective action of the corticosteroids prednisolone, hydrocortisone, and dexamethasone has been shown on a hypothetical model of myasthenia gravis, using the rat phrenic nerve-diaphragm preparation treated with hemicholinium-3. Dexamethasone is much more effective than prednisolone, and hydrocortisone is the least effective. Prednisolone has no effect on a neuromuscular block caused by choline, decamethonium, physostigmine, d-tubocurarine, and a high or low calcium ion concentration. The possible implications of the present study for myasthenic disease are discussed. It is tentatively concluded that the site of action of corticosteroids in myasthenia gravis is located presynaptically.", "contents": "Effect of corticosteroids on the phrenic nerve-diaphragm of preparation treated with hemicholinium. A possible model of myasthenia gravis. A marked protective action of the corticosteroids prednisolone, hydrocortisone, and dexamethasone has been shown on a hypothetical model of myasthenia gravis, using the rat phrenic nerve-diaphragm preparation treated with hemicholinium-3. Dexamethasone is much more effective than prednisolone, and hydrocortisone is the least effective. Prednisolone has no effect on a neuromuscular block caused by choline, decamethonium, physostigmine, d-tubocurarine, and a high or low calcium ion concentration. The possible implications of the present study for myasthenic disease are discussed. It is tentatively concluded that the site of action of corticosteroids in myasthenia gravis is located presynaptically."} {"id": "PMID:180453", "title": "Alexander's disease: a report and reappraisal.", "content": "A boy with juvenile onset of symptoms of Alexander's disease had a clinical picture of pseudobulbar palsy, ataxia, and spastic paraparesis. Pathologic examination of the central nervous system revealed the diffuse presence of Rosenthal fibers and patchy demyelination. This may be the first report of a case with significant neuronal changes and inflammation within the brain stem in this disease. The clinical picture of this entity is varied and age-dependent. Alexander's disease may be a motor system specific entity secondary to astrocytic dysfunction.", "contents": "Alexander's disease: a report and reappraisal. A boy with juvenile onset of symptoms of Alexander's disease had a clinical picture of pseudobulbar palsy, ataxia, and spastic paraparesis. Pathologic examination of the central nervous system revealed the diffuse presence of Rosenthal fibers and patchy demyelination. This may be the first report of a case with significant neuronal changes and inflammation within the brain stem in this disease. The clinical picture of this entity is varied and age-dependent. Alexander's disease may be a motor system specific entity secondary to astrocytic dysfunction."} {"id": "PMID:180454", "title": "A possible mechanism for selective cerebellar damage in partial pyruvate dehydrogenase deficiency.", "content": "In patients with partial deficiencies of pyruvate dehydrogenase, cerebellar ataxia has been the most prominent and sometimes the only neurologic abnormality. It is not clear how this generalized enzyme deficiency (with activity 15 to 30 percent of normal in several tissues) might lead to clinical signs referable to a limited part of the nervous system. We therefore compared the normal activity of pyruvate dehydrogenase with the normal rate of pyruvate oxidation in different parts of animal brains and then calculated the effect on pyruvate oxidation of partial deficiencies of the enzyme. The data indicate that pyruvate oxidation could be impaired in an area of anterior cerebellar vermis by deficiencies of pyruvate dehydrogenase too mild to affect pyruvate oxidation in the other areas of the brain we examined.", "contents": "A possible mechanism for selective cerebellar damage in partial pyruvate dehydrogenase deficiency. In patients with partial deficiencies of pyruvate dehydrogenase, cerebellar ataxia has been the most prominent and sometimes the only neurologic abnormality. It is not clear how this generalized enzyme deficiency (with activity 15 to 30 percent of normal in several tissues) might lead to clinical signs referable to a limited part of the nervous system. We therefore compared the normal activity of pyruvate dehydrogenase with the normal rate of pyruvate oxidation in different parts of animal brains and then calculated the effect on pyruvate oxidation of partial deficiencies of the enzyme. The data indicate that pyruvate oxidation could be impaired in an area of anterior cerebellar vermis by deficiencies of pyruvate dehydrogenase too mild to affect pyruvate oxidation in the other areas of the brain we examined."} {"id": "PMID:180455", "title": "Melanosis of the choroid plexua.", "content": "A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland.", "contents": "Melanosis of the choroid plexua. A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland."} {"id": "PMID:180456", "title": "Experimental alterations in cyclic adenosine monophosphate concentrations in the cat basilar artery.", "content": "Levels of cyclic adenosine monophosphate (AMP) in the basilar artery and in circulating blood of cats were determined after the production of spasm by topical application of blood to the vessel and following treatment with agents known to alter cyclic AMP. Isoproterenol, known to stimulate adenyl cyclase, and aminophylline, a phosphodiesterase inhibitor, were studied alone and in combination. Cyclic AMP of the basilar artery fell from a mean control value of 43 to 26 pmoles per milligram of protein following the production of vasospasm. Intravenous administration of isoproterenol alone and in combination with aminophylline produced dilatation of the basilar artery, which was associated with a marked rise in the cyclic AMP concentration in the vessel. The finding that cerebral vasospasm is associated with a fall and vasodilation with a rise in cyclic AMP concentration supports the hypothesis of an active role for cyclic nucleotides in the regulation of cerebrovascular smooth muscle tone.", "contents": "Experimental alterations in cyclic adenosine monophosphate concentrations in the cat basilar artery. Levels of cyclic adenosine monophosphate (AMP) in the basilar artery and in circulating blood of cats were determined after the production of spasm by topical application of blood to the vessel and following treatment with agents known to alter cyclic AMP. Isoproterenol, known to stimulate adenyl cyclase, and aminophylline, a phosphodiesterase inhibitor, were studied alone and in combination. Cyclic AMP of the basilar artery fell from a mean control value of 43 to 26 pmoles per milligram of protein following the production of vasospasm. Intravenous administration of isoproterenol alone and in combination with aminophylline produced dilatation of the basilar artery, which was associated with a marked rise in the cyclic AMP concentration in the vessel. The finding that cerebral vasospasm is associated with a fall and vasodilation with a rise in cyclic AMP concentration supports the hypothesis of an active role for cyclic nucleotides in the regulation of cerebrovascular smooth muscle tone."} {"id": "PMID:180458", "title": "[The central or peripheral nature of pain in essential headaches].", "content": "As an alternative to the conventional peripheral (vascular or chemical) thesis, the possibility of the central origin of pain in essential headaches is illustrated. In fact, observations carried out on animal and man reveal that, central pain, besides being organic, may be of a functional nature. It may be correlated to the lack of those biochemical mechanisms, which take place in the assimilation of those painful inputs at a cerebral level. Particularly pain may be caused by a lack of the 5HT turn-over. As a result of experiments carried out on animals, this takes the role of mediating pain inhibition, being present in the modulation stage of those multi-integrated processes which permit the central perception of pain. Some biochemical and pharmacological clinical observations suggest a serotonin lack in patients affected by essential headaches. A special interest is established by the reciprocal involvement of ancestral functions in essential headaches, such as: emotion, sleep, appetite, vomit, thermoregulation and sex, which are functions directly or undirectly controlled by serotonin. In the therapeutic field, the apparent contradiction between the benefit achieved by anti-serotonin drugs (such as: ergotamine, methisergide, org. G.C. 94 and LSD-25 at non-hallucinogen doses) and the substances with pro-serotonin activity (L-triptophane and L-5 hydroxy-triptophane) supports the hypothesis of a central lack of 5HT, due to the fact that the recent experiments on animal and man have shown a serotonin compatibility by \"antiserotonin\" drugs, when they are administered at therapeutic doses. If this initial thesis finds further confirmations, we could define essential headaches as a peculiar \"pain disease\", thus allowing them a well defined nosologic classification.", "contents": "[The central or peripheral nature of pain in essential headaches]. As an alternative to the conventional peripheral (vascular or chemical) thesis, the possibility of the central origin of pain in essential headaches is illustrated. In fact, observations carried out on animal and man reveal that, central pain, besides being organic, may be of a functional nature. It may be correlated to the lack of those biochemical mechanisms, which take place in the assimilation of those painful inputs at a cerebral level. Particularly pain may be caused by a lack of the 5HT turn-over. As a result of experiments carried out on animals, this takes the role of mediating pain inhibition, being present in the modulation stage of those multi-integrated processes which permit the central perception of pain. Some biochemical and pharmacological clinical observations suggest a serotonin lack in patients affected by essential headaches. A special interest is established by the reciprocal involvement of ancestral functions in essential headaches, such as: emotion, sleep, appetite, vomit, thermoregulation and sex, which are functions directly or undirectly controlled by serotonin. In the therapeutic field, the apparent contradiction between the benefit achieved by anti-serotonin drugs (such as: ergotamine, methisergide, org. G.C. 94 and LSD-25 at non-hallucinogen doses) and the substances with pro-serotonin activity (L-triptophane and L-5 hydroxy-triptophane) supports the hypothesis of a central lack of 5HT, due to the fact that the recent experiments on animal and man have shown a serotonin compatibility by \"antiserotonin\" drugs, when they are administered at therapeutic doses. If this initial thesis finds further confirmations, we could define essential headaches as a peculiar \"pain disease\", thus allowing them a well defined nosologic classification."} {"id": "PMID:180459", "title": "[Morphological substrate of antalgia and analgesia in the odontostomatological and facial area].", "content": "Prior personal work is further extended by a description of the way in which odontostomatological and facial pain is sedated by acupuncture: via peripheral receptors, whose stimulations are intercepted and modulated by various filters lying between the periphery and the cortex: cord (gelatinous substance of Rolando, gate control system), reticular formation and thalamocortical pathways.", "contents": "[Morphological substrate of antalgia and analgesia in the odontostomatological and facial area]. Prior personal work is further extended by a description of the way in which odontostomatological and facial pain is sedated by acupuncture: via peripheral receptors, whose stimulations are intercepted and modulated by various filters lying between the periphery and the cortex: cord (gelatinous substance of Rolando, gate control system), reticular formation and thalamocortical pathways."} {"id": "PMID:180460", "title": "[Acupuncture and relaxation].", "content": "Relaxation and tranquility are commonly induced by acupuncture. Techniques are presented and neurophysiological theories underlying the therapeutic effect are discussed. Emphasis is laid on the importance of this effect in psychiatric management.", "contents": "[Acupuncture and relaxation]. Relaxation and tranquility are commonly induced by acupuncture. Techniques are presented and neurophysiological theories underlying the therapeutic effect are discussed. Emphasis is laid on the importance of this effect in psychiatric management."} {"id": "PMID:180465", "title": "Serum testosterone and dihydrotestosterone in patients with trophoblastic disease.", "content": "Serum testosterone (T) and dihydrotestosterone (DHT) were measured by radioimmunoassay in 14 patients with unaborted hydatidiform mole and in 16 patients with normal pregnancy of similar gestational age. Serum human chorionic gonadotropin (hCG) was measured by the radioreceptor assay in patients with hydatidiform mole. Serum T ranged from 0.27 to 5.39 ng/ml with a mean +/- SE of 2.21 +/- 0.45 ng/ml in patients with hydatidiform mole mole and from 0.20 to 2.40 ng/ml with a mean +/- SE of 0.80 +/- 0.14 ng/ml in patients with normal pregnancy, the difference being statistically significant (P = less than 0.005). Similarly, patients with molar pregnancies had a significantly higher (P = less than 0.005) serum DHT (range: 0.09 to 0.62 ng/ml; mean +/- SE: 0.29 +/- 0.05 ng/ml) than patients with normal pregnancies (range: 0.04 to 0.28 ng/ml; mean +/- SE 0.12 +/- 0.02 ng/ml). There was no significant correlation between uterine size or serum hCG and serum T or DHT. The possible sources of the elevated serum T and DHT and the lack of hirsutism or virilization in patients with trophoblastic disease are discussed.", "contents": "Serum testosterone and dihydrotestosterone in patients with trophoblastic disease. Serum testosterone (T) and dihydrotestosterone (DHT) were measured by radioimmunoassay in 14 patients with unaborted hydatidiform mole and in 16 patients with normal pregnancy of similar gestational age. Serum human chorionic gonadotropin (hCG) was measured by the radioreceptor assay in patients with hydatidiform mole. Serum T ranged from 0.27 to 5.39 ng/ml with a mean +/- SE of 2.21 +/- 0.45 ng/ml in patients with hydatidiform mole mole and from 0.20 to 2.40 ng/ml with a mean +/- SE of 0.80 +/- 0.14 ng/ml in patients with normal pregnancy, the difference being statistically significant (P = less than 0.005). Similarly, patients with molar pregnancies had a significantly higher (P = less than 0.005) serum DHT (range: 0.09 to 0.62 ng/ml; mean +/- SE: 0.29 +/- 0.05 ng/ml) than patients with normal pregnancies (range: 0.04 to 0.28 ng/ml; mean +/- SE 0.12 +/- 0.02 ng/ml). There was no significant correlation between uterine size or serum hCG and serum T or DHT. The possible sources of the elevated serum T and DHT and the lack of hirsutism or virilization in patients with trophoblastic disease are discussed."} {"id": "PMID:180466", "title": "Association of liver tumors with oral contraceptives.", "content": "Benign hepatocellular neoplasia occurring in 22 women receiving oral contraceptive steroids but no other known hepatotoxins is reported for the first time from a registry for liver tumors associated with oral contraceptives. A review of recent literature has yielded 45 cases including 3 previously reported by the authors. This striking increase in what were formerly rare primary liver tumors in young women strongly suggests a cause and effect of relationship. Eighteen patients presented with intrahepatic or extrahepatic rupture and hemoperitoneum with hemorrhagic shock due to vascular changes within their liver tumors. Five died as a direct or indirect result of preoperative or postoperative blood loss. The predominant lesions were focal nodular hyperplasia, hepatic adenoma, and hamartoma. Multiple synonymous nomenclature used to describe the histopathology of these tumors is disquieting and requires clarification. For diagnosis, enzyme determinations are not helpful. However, radionucleide liver scans, sonography, and celiac arteriography may be of value. Clinical surveillance must be the primary means for identification of this potentially lethal adverse phenomenon among 50,000,000 oral contraceptive users.", "contents": "Association of liver tumors with oral contraceptives. Benign hepatocellular neoplasia occurring in 22 women receiving oral contraceptive steroids but no other known hepatotoxins is reported for the first time from a registry for liver tumors associated with oral contraceptives. A review of recent literature has yielded 45 cases including 3 previously reported by the authors. This striking increase in what were formerly rare primary liver tumors in young women strongly suggests a cause and effect of relationship. Eighteen patients presented with intrahepatic or extrahepatic rupture and hemoperitoneum with hemorrhagic shock due to vascular changes within their liver tumors. Five died as a direct or indirect result of preoperative or postoperative blood loss. The predominant lesions were focal nodular hyperplasia, hepatic adenoma, and hamartoma. Multiple synonymous nomenclature used to describe the histopathology of these tumors is disquieting and requires clarification. For diagnosis, enzyme determinations are not helpful. However, radionucleide liver scans, sonography, and celiac arteriography may be of value. Clinical surveillance must be the primary means for identification of this potentially lethal adverse phenomenon among 50,000,000 oral contraceptive users."} {"id": "PMID:180470", "title": "Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas.", "content": "The use of the blood-brain barrier and of tumor-specific antibodies to concentrate boron selectivity in gliomas for neutron capture therapy is considered experimentally and theoretically. The time-dependent concentration of two anionic boranes, B12 H11 SH2- and B12 H11 SOSB12 H114-, in the blood, brain, and tumor of rats bearing a tumor of gliomatous origin is reported. The rate of clearance of each anionic borane from the blood is correlated with the fraction of non-protein bound anion in the plasma. The use of antibodies to carry therapeutical useful amounts of boron to tumor-specific or tumor-associated antigens on the tumor cell surface will require different numbers of boron atoms bound per antibody depending on several immunological and physical parameters. Calculations using published values of antibody-antigen association constants and of cell surface antigen densities predict that in order to obtain 10mug 10B/g tumor from 10 to over 10,000 boron-10 atoms will have to be bound per tumor antigenic site.", "contents": "Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas. The use of the blood-brain barrier and of tumor-specific antibodies to concentrate boron selectivity in gliomas for neutron capture therapy is considered experimentally and theoretically. The time-dependent concentration of two anionic boranes, B12 H11 SH2- and B12 H11 SOSB12 H114-, in the blood, brain, and tumor of rats bearing a tumor of gliomatous origin is reported. The rate of clearance of each anionic borane from the blood is correlated with the fraction of non-protein bound anion in the plasma. The use of antibodies to carry therapeutical useful amounts of boron to tumor-specific or tumor-associated antigens on the tumor cell surface will require different numbers of boron atoms bound per antibody depending on several immunological and physical parameters. Calculations using published values of antibody-antigen association constants and of cell surface antigen densities predict that in order to obtain 10mug 10B/g tumor from 10 to over 10,000 boron-10 atoms will have to be bound per tumor antigenic site."} {"id": "PMID:180471", "title": "Methotrexate with leucovorin rescue in the treatment of gynecologic malignancies. Preliminary report.", "content": "Experience with chemotherapy in advanced gynecologic malignancies is limited. In 6 patients, 2 of 4 with carcinoma of the cervix, and 1 patient with carcinoma of the ovary achieved partial remission when treated with a regimen of high dose methotrexate (240 mg/m2) followed by leucovorin rescue. On patient with metastatic trophoblastic disease achieved complete response (greater than 24 months). The number of doses of leucovorin 'rescue' was based on creatinine clearance. The advantage of rapid response and moderate toxicity indicate the need for further study of this regimen in the treatment of gynecologic malignancies.", "contents": "Methotrexate with leucovorin rescue in the treatment of gynecologic malignancies. Preliminary report. Experience with chemotherapy in advanced gynecologic malignancies is limited. In 6 patients, 2 of 4 with carcinoma of the cervix, and 1 patient with carcinoma of the ovary achieved partial remission when treated with a regimen of high dose methotrexate (240 mg/m2) followed by leucovorin rescue. On patient with metastatic trophoblastic disease achieved complete response (greater than 24 months). The number of doses of leucovorin 'rescue' was based on creatinine clearance. The advantage of rapid response and moderate toxicity indicate the need for further study of this regimen in the treatment of gynecologic malignancies."} {"id": "PMID:180474", "title": "[Burkitt's lymphoma (author's transl)].", "content": "Burkitt's lymphoma occurs endemically in Central Africa, but is also found sporadically in areas with temperate climate. A case of Burkitt's lymphoma found in our area is described. The literature in regard to the clinical symptoms, etiology and treatment of Burkitt's lymphoma is reviewed. At the present time cyclophosphamide is considered to be the drug of choice; it leads to a remission rate of about 90%.", "contents": "[Burkitt's lymphoma (author's transl)]. Burkitt's lymphoma occurs endemically in Central Africa, but is also found sporadically in areas with temperate climate. A case of Burkitt's lymphoma found in our area is described. The literature in regard to the clinical symptoms, etiology and treatment of Burkitt's lymphoma is reviewed. At the present time cyclophosphamide is considered to be the drug of choice; it leads to a remission rate of about 90%."} {"id": "PMID:180476", "title": "Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field.", "content": "Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar.", "contents": "Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field. Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar."} {"id": "PMID:180477", "title": "[Permissivity of mouse-man hybrid cell clones to three enteroviruses: poliovirus II, coxsackie B3 and echovirus 11. Role of human chromosome F. 19 (author's transl)].", "content": "The permissivity of human cells to enteroviruses is linked to the presence of specific cell receptors. Owing to the chance elimination of human chromosomes, the man-mouse hybrid cells may be permissive or not depending on the genome responsible for synthesis of the receptors, and whether it has been conserved or not. By comparison of the cytopathogenic effects and virus production after inoculation of the viruses Polio II, Echo 11 and Coxsachie B3 to various hybrid strains, we observed an identity of the spectrum of permissivity to these three viruses. The enzyme study revealed a very high correlation between this permissivity and expression by the clones of the human glucose phosphate isomerase enzyme, of which the structural gene was localised on chromosome F 19. These results suggest the presence on this chromosome of a gene or syntenic genes, governing the synthesis of specific cell receptors to the viruses studied.", "contents": "[Permissivity of mouse-man hybrid cell clones to three enteroviruses: poliovirus II, coxsackie B3 and echovirus 11. Role of human chromosome F. 19 (author's transl)]. The permissivity of human cells to enteroviruses is linked to the presence of specific cell receptors. Owing to the chance elimination of human chromosomes, the man-mouse hybrid cells may be permissive or not depending on the genome responsible for synthesis of the receptors, and whether it has been conserved or not. By comparison of the cytopathogenic effects and virus production after inoculation of the viruses Polio II, Echo 11 and Coxsachie B3 to various hybrid strains, we observed an identity of the spectrum of permissivity to these three viruses. The enzyme study revealed a very high correlation between this permissivity and expression by the clones of the human glucose phosphate isomerase enzyme, of which the structural gene was localised on chromosome F 19. These results suggest the presence on this chromosome of a gene or syntenic genes, governing the synthesis of specific cell receptors to the viruses studied."} {"id": "PMID:180478", "title": "[Tubular inclusions in the lymphocytes in a case of \"hairy cells leukemia\" (author's transl)].", "content": "A tubular inclusion (Hovig type) was found in the cytoplasm of the blood lymphocytes of a case of hairy cells leukemia. Its cytochemical and ultrastructural features are described ; its signification remains unknown.", "contents": "[Tubular inclusions in the lymphocytes in a case of \"hairy cells leukemia\" (author's transl)]. A tubular inclusion (Hovig type) was found in the cytoplasm of the blood lymphocytes of a case of hairy cells leukemia. Its cytochemical and ultrastructural features are described ; its signification remains unknown."} {"id": "PMID:180479", "title": "Submicroscopic response of articular chondrocytes to a cholesterol-containing diet.", "content": "10 days' to 3 months' consumption of a diet containing 4% cholesterol causes a minor and transitory stimulation of articular chondrocytes of mice. The transitory disturbance is accompanied by a more permanent increase in glycogen, by abnormal deposition of cytoplasmic lipid and by an increase in the fibrillarity of the pericellular matrix. The changes are consistent with the failure of the cholesterol diet to influence the course of osteoarthrosis if fed to mice from an early age through life.", "contents": "Submicroscopic response of articular chondrocytes to a cholesterol-containing diet. 10 days' to 3 months' consumption of a diet containing 4% cholesterol causes a minor and transitory stimulation of articular chondrocytes of mice. The transitory disturbance is accompanied by a more permanent increase in glycogen, by abnormal deposition of cytoplasmic lipid and by an increase in the fibrillarity of the pericellular matrix. The changes are consistent with the failure of the cholesterol diet to influence the course of osteoarthrosis if fed to mice from an early age through life."} {"id": "PMID:180480", "title": "Histogenesis of hyperplasia and carcinomas of the liver arising around central veins in mice ingesting chlorinated hydrocarbons.", "content": "The development of hyperplastic and neoplastic lesions of parenchymal cells of the liver adjacent to central veins was observed in C3H mice ingesting the chlorinated hydrocarbons, dieldrin or aldrin, in the diet. Lesions could be followed from pericentral hyperplasia to areas of hyperplasia, nodules of hyperplasia, small hepatocellular carcinomas, and large well-developed carcinomas, occasionally with metastases. Sometimes pericentral hyperplasia was diffuse throughout most or all of one lobe of the liver. These hyperplastic cells collided to become one large nodule and also one large carcinoma. The carcinomas were well-differentiated or moderately well-differentiated and grew on transplantation to isologous hosts. Histologically, the hyperplastic cells adjacent to central veins were increased in size, frequently with double nuclei. Carcinoma cells varied in size and shape and were huge with large nuclei, prominent nucleoli, and eosinophilic cytoplasm. Similar hepatocellular carcinomas were seen previously with carbon tetrachloride, another organochlorine chemical.", "contents": "Histogenesis of hyperplasia and carcinomas of the liver arising around central veins in mice ingesting chlorinated hydrocarbons. The development of hyperplastic and neoplastic lesions of parenchymal cells of the liver adjacent to central veins was observed in C3H mice ingesting the chlorinated hydrocarbons, dieldrin or aldrin, in the diet. Lesions could be followed from pericentral hyperplasia to areas of hyperplasia, nodules of hyperplasia, small hepatocellular carcinomas, and large well-developed carcinomas, occasionally with metastases. Sometimes pericentral hyperplasia was diffuse throughout most or all of one lobe of the liver. These hyperplastic cells collided to become one large nodule and also one large carcinoma. The carcinomas were well-differentiated or moderately well-differentiated and grew on transplantation to isologous hosts. Histologically, the hyperplastic cells adjacent to central veins were increased in size, frequently with double nuclei. Carcinoma cells varied in size and shape and were huge with large nuclei, prominent nucleoli, and eosinophilic cytoplasm. Similar hepatocellular carcinomas were seen previously with carbon tetrachloride, another organochlorine chemical."} {"id": "PMID:180483", "title": "Genetics and the etiology of childhood cancer.", "content": "A consideration of the world-wide incidences of childhood cancer and of hereditary subgroups leads to the conclusion that two successive mutations can initiate cancer cells and that such cells usually proceed to develop into detectable cancers in a period of time which is short compared with the time required for most adult cancers. Environmental carcinogens could hypothetically increase the rates at which these mutations occur, but they probably, in fact, contribute little to the incidences. Certain exceptions, notably leukemia and lymphoma, are noteworthy, and a viral origin for them has been widely hypothesized. If most solid tumors of childhood are indeed correctly attributable to mutations in germ and/or somatic cells, then the prospect for the prevention of childhood cancer becomes very dim. In fact, the incidence of the germinal forms may increase as treatment improves (18). In theory, one might be able to identify individuals harboring cancer genes germinally and even to identify them prenatally. But even if the burden of cancer attributable to the hereditary subgroups were elimanted, there would still remain the larger nonhereditary group resulting from somatic mutations. If this hypothesis is correct, then childhood cancer cannot be prevented. With this conclusion goes the admonition, however, that environmental mutagens might significantly increase the burden of childhood cancer. One such mutagen, therapeutic radiation, is known to increase the prospect that second tumors will occur in patients who carry a germinal cancer mutation. The major effort to reduce the incidence of childhood cancer by prevention should be spent in examining the possibility that leukemia and lymphoma are viral in origin. If the arguments presented are correct, then the main effort against childhood cancer must be that of early diagnosis and treatment. I realize that many have already argued for that strategy in the approach to cancer generally, but I now believe that it is particularly relevant to any program against cancer in children.", "contents": "Genetics and the etiology of childhood cancer. A consideration of the world-wide incidences of childhood cancer and of hereditary subgroups leads to the conclusion that two successive mutations can initiate cancer cells and that such cells usually proceed to develop into detectable cancers in a period of time which is short compared with the time required for most adult cancers. Environmental carcinogens could hypothetically increase the rates at which these mutations occur, but they probably, in fact, contribute little to the incidences. Certain exceptions, notably leukemia and lymphoma, are noteworthy, and a viral origin for them has been widely hypothesized. If most solid tumors of childhood are indeed correctly attributable to mutations in germ and/or somatic cells, then the prospect for the prevention of childhood cancer becomes very dim. In fact, the incidence of the germinal forms may increase as treatment improves (18). In theory, one might be able to identify individuals harboring cancer genes germinally and even to identify them prenatally. But even if the burden of cancer attributable to the hereditary subgroups were elimanted, there would still remain the larger nonhereditary group resulting from somatic mutations. If this hypothesis is correct, then childhood cancer cannot be prevented. With this conclusion goes the admonition, however, that environmental mutagens might significantly increase the burden of childhood cancer. One such mutagen, therapeutic radiation, is known to increase the prospect that second tumors will occur in patients who carry a germinal cancer mutation. The major effort to reduce the incidence of childhood cancer by prevention should be spent in examining the possibility that leukemia and lymphoma are viral in origin. If the arguments presented are correct, then the main effort against childhood cancer must be that of early diagnosis and treatment. I realize that many have already argued for that strategy in the approach to cancer generally, but I now believe that it is particularly relevant to any program against cancer in children."} {"id": "PMID:180484", "title": "Growth and growth velocity of lean body mass and fat in adolescent boys.", "content": "Beginning at age 10 years, height, weight, body density, and bone age of 40 normal boys were measured yearly over a period of 8 years. From body density, lean body mass and body content of fat were calculated. Values for all measurements are included in the Appendix and mean values, including those for lean body mass and percentage of body fat, are presented for each year in Table 1. Coefficients of correlation between measurements made during the first and eighth years of study were high for height (0.68), weight (0.50), and lean body mass (0.60), but relatively low for body fat (0.25). Correlation coefficients between the various parameters in a given year are presented in Table 2. The maximum yearly increment in height, weight, and lean body mass of individual subjects coincided in time. The respective mean values for the year of maximum growth were 9.4 cm, 8.1 kg, and 7.5 kg. Throughout the growth spurt, the contribution of fat to increase in body weight was small. It may be concluded that, next to height, the absolute amount of lean body mass demonstrates the most constant trend of development during adolescence.", "contents": "Growth and growth velocity of lean body mass and fat in adolescent boys. Beginning at age 10 years, height, weight, body density, and bone age of 40 normal boys were measured yearly over a period of 8 years. From body density, lean body mass and body content of fat were calculated. Values for all measurements are included in the Appendix and mean values, including those for lean body mass and percentage of body fat, are presented for each year in Table 1. Coefficients of correlation between measurements made during the first and eighth years of study were high for height (0.68), weight (0.50), and lean body mass (0.60), but relatively low for body fat (0.25). Correlation coefficients between the various parameters in a given year are presented in Table 2. The maximum yearly increment in height, weight, and lean body mass of individual subjects coincided in time. The respective mean values for the year of maximum growth were 9.4 cm, 8.1 kg, and 7.5 kg. Throughout the growth spurt, the contribution of fat to increase in body weight was small. It may be concluded that, next to height, the absolute amount of lean body mass demonstrates the most constant trend of development during adolescence."} {"id": "PMID:180485", "title": "Intestinal phosphate transport in familial hypophosphatemic rickets.", "content": "The present report outlines an attempt to characterize inorganic phosphate uptake by human jejunal mucosa using biopsy material obtained from six patients affected by the X-linked form of vitamin D-resistant rickets and six control subjects. The tissue from control subjects accumulated 32P actively in a linear fashion against time. The incorporation of inorganic phosphate into organophosphate derivatives is rapid and equilibrates after 10 min at an inorganic over total phosphate ratio of 0.45. Concentrative uptake and incorporation were both suppressed by anaerobiosis or cyanide. Rates of phosphate uptake and incorporation into the organic derivatives by the tissue of hypophosphatemic patients are comparable with normal values. Saturation kinetics observed over a wide range of substrate concentrations (0.003 to 3 mM) elicits only one transport system with an apparent Michaelis constant of 0.2 mM and a maximum velocity of 0.7 mmol/liter/40 min. The kinetic data obtained from the patients do not strikingly differ from the control values. The chemical analysis of the phosphate content of intestinal mucosa from two patients and two control subjects indicates that the tissue is not specifically phosphate-depleted in the mutant individuals. These results are in accordance with the positive results obtained with the oral replacement therapy in familial hypophosphatemia.", "contents": "Intestinal phosphate transport in familial hypophosphatemic rickets. The present report outlines an attempt to characterize inorganic phosphate uptake by human jejunal mucosa using biopsy material obtained from six patients affected by the X-linked form of vitamin D-resistant rickets and six control subjects. The tissue from control subjects accumulated 32P actively in a linear fashion against time. The incorporation of inorganic phosphate into organophosphate derivatives is rapid and equilibrates after 10 min at an inorganic over total phosphate ratio of 0.45. Concentrative uptake and incorporation were both suppressed by anaerobiosis or cyanide. Rates of phosphate uptake and incorporation into the organic derivatives by the tissue of hypophosphatemic patients are comparable with normal values. Saturation kinetics observed over a wide range of substrate concentrations (0.003 to 3 mM) elicits only one transport system with an apparent Michaelis constant of 0.2 mM and a maximum velocity of 0.7 mmol/liter/40 min. The kinetic data obtained from the patients do not strikingly differ from the control values. The chemical analysis of the phosphate content of intestinal mucosa from two patients and two control subjects indicates that the tissue is not specifically phosphate-depleted in the mutant individuals. These results are in accordance with the positive results obtained with the oral replacement therapy in familial hypophosphatemia."} {"id": "PMID:180487", "title": "Chemoreceptor function and sleep state in apnea.", "content": "Resting ventilation and ventilatory responses to 100% oxygen and to 5% carbon dioxide in air were measured in REM and non-REM sleep in post-neonatal infants. Normal controls were compared to infants with prolonged apnea and to siblings of sudden infant death victims. No significant differences in ventilatory responses were found between the groups. We conclude that apnea may occur in infants whose central and peripheral chemoreceptor activity is normal while they are breathing.", "contents": "Chemoreceptor function and sleep state in apnea. Resting ventilation and ventilatory responses to 100% oxygen and to 5% carbon dioxide in air were measured in REM and non-REM sleep in post-neonatal infants. Normal controls were compared to infants with prolonged apnea and to siblings of sudden infant death victims. No significant differences in ventilatory responses were found between the groups. We conclude that apnea may occur in infants whose central and peripheral chemoreceptor activity is normal while they are breathing."} {"id": "PMID:180488", "title": "Computerized tomography in the detection of intracranial metastases in children.", "content": "Computerized tomography brain scans produce sectional tomograms of the brain substance which demonstrate intracranial lesions. The procedure is safe and painless, and can be done on an outpatient basis. Three children with malignant disease had intracranial metastases demonstrated using this technique during a recent six-month period at the Cleveland Clinic.", "contents": "Computerized tomography in the detection of intracranial metastases in children. Computerized tomography brain scans produce sectional tomograms of the brain substance which demonstrate intracranial lesions. The procedure is safe and painless, and can be done on an outpatient basis. Three children with malignant disease had intracranial metastases demonstrated using this technique during a recent six-month period at the Cleveland Clinic."} {"id": "PMID:180501", "title": "A transovarian transmission study of Marek's disease in Japanese quail.", "content": "Experiments were conducted to determine if transovarian transmission of the JM strain of Marek's disease virus (MDV) occurs in Japanese quail. In one experiment, parent quail were infected with MDV when one-day-old; in another experiment, parent quail were infected when seven weeks old. No precipitating antigen or cytopathic or infective agent was isolated from the egg yolks, embryos, newly hatched quail, or progeny quail of the infected parents. During the eight weeks observation period, the progeny of infected parents showed no clinical symptoms, mortality, gross or microscopic lesions, MD viremia, or antibody. However, an MD-specific fluorescent antigen was observed in fibroblast and kidney cell cultures from embryos of parents infected at one day of age. Approximately 10% of the embryos contained this fluorescent antigen. Fluorescent antigen was not observed in cultures from embryos of quail infected at the age of seven weeks or control quail.", "contents": "A transovarian transmission study of Marek's disease in Japanese quail. Experiments were conducted to determine if transovarian transmission of the JM strain of Marek's disease virus (MDV) occurs in Japanese quail. In one experiment, parent quail were infected with MDV when one-day-old; in another experiment, parent quail were infected when seven weeks old. No precipitating antigen or cytopathic or infective agent was isolated from the egg yolks, embryos, newly hatched quail, or progeny quail of the infected parents. During the eight weeks observation period, the progeny of infected parents showed no clinical symptoms, mortality, gross or microscopic lesions, MD viremia, or antibody. However, an MD-specific fluorescent antigen was observed in fibroblast and kidney cell cultures from embryos of parents infected at one day of age. Approximately 10% of the embryos contained this fluorescent antigen. Fluorescent antigen was not observed in cultures from embryos of quail infected at the age of seven weeks or control quail."} {"id": "PMID:180502", "title": "Efficacy of turkey herpesvirus vaccine when administered simultaneously with fowl pox vaccine.", "content": "The efficacy of the turkey herpesvirus (HVT) vaccine in protecting chickens challenged with virulent Marek's disease (MD) virus was unaffected by the presence of either the chick embryo fowl pox vaccine or fowl pox vaccine derived from cell culture. Conversely the HVT vaccine did not affect the efficacy of the fowl pox vaccine in chickens challenged with pathogenic fowl pox virus. A combination of spectinomycin dihydrochloride pentahydrate and lincomycin hydrochloride monohydrate as well as spectinomycin sulfate tetrahydrate were found to be compatible with the HVT and fowl pox vaccines as demonstrated by resistance after challenge with virulent MD virus or fowl pox virus.", "contents": "Efficacy of turkey herpesvirus vaccine when administered simultaneously with fowl pox vaccine. The efficacy of the turkey herpesvirus (HVT) vaccine in protecting chickens challenged with virulent Marek's disease (MD) virus was unaffected by the presence of either the chick embryo fowl pox vaccine or fowl pox vaccine derived from cell culture. Conversely the HVT vaccine did not affect the efficacy of the fowl pox vaccine in chickens challenged with pathogenic fowl pox virus. A combination of spectinomycin dihydrochloride pentahydrate and lincomycin hydrochloride monohydrate as well as spectinomycin sulfate tetrahydrate were found to be compatible with the HVT and fowl pox vaccines as demonstrated by resistance after challenge with virulent MD virus or fowl pox virus."} {"id": "PMID:180498", "title": "[Specific rabbit abtiserum against human chylomicrons and very low density lipoproteins].", "content": "Rabbits were immunized by repeated intravenous injections of large amounts of chylomicrons plus VLDL isolated from human lipemic plasmas. The antisera were absorbed usccessively with lipoprotein free serum, HDL and LDL2. The absorbed antisera still precipitate chylomicrons and VLDL from sera of normal and hyperlipemic subjects (post-absorptive donors and fasting patients with type IV and type V hyperlipoproteinemia). By gel diffusion methods (immunoelectrophoresis and double diffusion in two dimensions), the antisera reveal a single precipitin line which stains better for lipid than for protein. This line is pronounced in VLDL-rich sera and absent in VLDL-free sera. The antisera react with chylomicrons plus VLDL delipidated by extraction with ethanol/diethyl ether; this shows that the antigenic site is an apoprotein; in contrast to apoprotein C, this apoprotein appears to be unique to the triglyceride-rich lipoproteins.", "contents": "[Specific rabbit abtiserum against human chylomicrons and very low density lipoproteins]. Rabbits were immunized by repeated intravenous injections of large amounts of chylomicrons plus VLDL isolated from human lipemic plasmas. The antisera were absorbed usccessively with lipoprotein free serum, HDL and LDL2. The absorbed antisera still precipitate chylomicrons and VLDL from sera of normal and hyperlipemic subjects (post-absorptive donors and fasting patients with type IV and type V hyperlipoproteinemia). By gel diffusion methods (immunoelectrophoresis and double diffusion in two dimensions), the antisera reveal a single precipitin line which stains better for lipid than for protein. This line is pronounced in VLDL-rich sera and absent in VLDL-free sera. The antisera react with chylomicrons plus VLDL delipidated by extraction with ethanol/diethyl ether; this shows that the antigenic site is an apoprotein; in contrast to apoprotein C, this apoprotein appears to be unique to the triglyceride-rich lipoproteins."} {"id": "PMID:180503", "title": "Marek's disease in Japanese quail -- a pathological, virological and serological study.", "content": "Experimental studies were performed to see whether Japanese quail (Coturnix coturnix japonica) are susceptible to JM strain of Marek's disease virus (MDV). In three identical trials, a total of 120, one-day-old quail were inoculated intra-abdominally with 0.2 ml. of chicken blood infected with MDV (JM strain) and raised in FAPP isolators. Uninfected controls were inoculated with normal saline only and raised separately. During the 18-week post infection observation period, 65-80% of the infected quail died within six weeks, while the highest mortality in control groups was only 0-5%. In each trial, ocular lesions with or without unilateral or bilateral blindness and signs of torticollis were evident in a few quail after 10-14 weeks. Gross and microscopic lesions suggestive of MD were observed 14 days on. The most pronounced lesions were observed in lungs. Neural tissues were least affected. In general, females were more susceptible than males. MD-specific fluorescent and precipitating antigens were detected in different visceral tissues, buffy coat and cultured macrophages of infected quail. Fluorescent antigen appeared at 6-7 days after infection, whereas precipitating antigen appeared after 12-15 days. Viral (MDV) infectivity tests in cell cultures and bioassay in one-day-old chicks and quail demonstrated that infected quail become viremic around the seventh day post infection. A cytopathic agent similar to MDV was also isolated from quail. Neither Newcastle disease virus nor a bacterial agent was isolated from the quail. MD-specific fluorescent precipitating antibodies were present in the egg yolk and plasma of both infected sick and infected symptomless quail. The earliest detectable plasma MD antibody appeared in 14-21 days. Such findings were not observed in quail from parent stock and controls. Our studies demonstrated that Japanese quail are susceptible to JM strain of MDV.", "contents": "Marek's disease in Japanese quail -- a pathological, virological and serological study. Experimental studies were performed to see whether Japanese quail (Coturnix coturnix japonica) are susceptible to JM strain of Marek's disease virus (MDV). In three identical trials, a total of 120, one-day-old quail were inoculated intra-abdominally with 0.2 ml. of chicken blood infected with MDV (JM strain) and raised in FAPP isolators. Uninfected controls were inoculated with normal saline only and raised separately. During the 18-week post infection observation period, 65-80% of the infected quail died within six weeks, while the highest mortality in control groups was only 0-5%. In each trial, ocular lesions with or without unilateral or bilateral blindness and signs of torticollis were evident in a few quail after 10-14 weeks. Gross and microscopic lesions suggestive of MD were observed 14 days on. The most pronounced lesions were observed in lungs. Neural tissues were least affected. In general, females were more susceptible than males. MD-specific fluorescent and precipitating antigens were detected in different visceral tissues, buffy coat and cultured macrophages of infected quail. Fluorescent antigen appeared at 6-7 days after infection, whereas precipitating antigen appeared after 12-15 days. Viral (MDV) infectivity tests in cell cultures and bioassay in one-day-old chicks and quail demonstrated that infected quail become viremic around the seventh day post infection. A cytopathic agent similar to MDV was also isolated from quail. Neither Newcastle disease virus nor a bacterial agent was isolated from the quail. MD-specific fluorescent precipitating antibodies were present in the egg yolk and plasma of both infected sick and infected symptomless quail. The earliest detectable plasma MD antibody appeared in 14-21 days. Such findings were not observed in quail from parent stock and controls. Our studies demonstrated that Japanese quail are susceptible to JM strain of MDV."} {"id": "PMID:180504", "title": "Effects of stress on the corticosterone content of the blood plasma and adrenal gland of intact and bursectomized Gallus domesticus.", "content": "The response of intact and bursectomized chicks to stressful stimuli has been examined. The stressors imposed were: a. fast-acting ACTH adminstration; b. immersion in cold water; c. starvation. In Bursa-intact chicks the results were as follows: 1. Plasma corticosterone was increased by all stimuli. 2. Adrenal corticosterone was decreased by ACTH treatment while it was increased by immersion in cold water and by starvation. 3. Plasma glucose was increased by ACTH administration and cold water immersion and decreased by starvation of the birds. 4. Adrenal ascorbic acid concentration was not influenced by all stimuli. 5. Adrenal weights were found to be increased by ACTH and starvation treatments only. 6. Bursa weights were increased by ACTH administration. 7. A very low concentration of corticosterone was found in the Bursa of Fabricius. Bursectomized chicks differed from the intact ones in the following: 1. Plasma and adrenal corticosterone concentrations were not increased by starvation. 2. Plasma glucose increased moderately with ACTH administration. 3. Adrenal ascorbic acid was depleted by all stimuli but was not related to the corticosterone level in the adrenals and blood plasma.", "contents": "Effects of stress on the corticosterone content of the blood plasma and adrenal gland of intact and bursectomized Gallus domesticus. The response of intact and bursectomized chicks to stressful stimuli has been examined. The stressors imposed were: a. fast-acting ACTH adminstration; b. immersion in cold water; c. starvation. In Bursa-intact chicks the results were as follows: 1. Plasma corticosterone was increased by all stimuli. 2. Adrenal corticosterone was decreased by ACTH treatment while it was increased by immersion in cold water and by starvation. 3. Plasma glucose was increased by ACTH administration and cold water immersion and decreased by starvation of the birds. 4. Adrenal ascorbic acid concentration was not influenced by all stimuli. 5. Adrenal weights were found to be increased by ACTH and starvation treatments only. 6. Bursa weights were increased by ACTH administration. 7. A very low concentration of corticosterone was found in the Bursa of Fabricius. Bursectomized chicks differed from the intact ones in the following: 1. Plasma and adrenal corticosterone concentrations were not increased by starvation. 2. Plasma glucose increased moderately with ACTH administration. 3. Adrenal ascorbic acid was depleted by all stimuli but was not related to the corticosterone level in the adrenals and blood plasma."} {"id": "PMID:180505", "title": "Specific and non-specific immunosuppression in chickens.", "content": "Specific immunosuppression, caused by the passive transfer of immune sera, and non-specific immunosuppression, caused by ACTH, were investigated for possible interactions. The data confirm earlier studies which show that both types of suppression when administered independently cause reductions in humoral immune responsiveness. However, when both suppressive methods were administered simultaneously a level of suppression occurred which was not greater than that caused by either method alone. Additionally, when ACTH-induced non-specific immunosuppression was established in donors, passive transfers of sera from these donors did not cause suppression in the recipients.", "contents": "Specific and non-specific immunosuppression in chickens. Specific immunosuppression, caused by the passive transfer of immune sera, and non-specific immunosuppression, caused by ACTH, were investigated for possible interactions. The data confirm earlier studies which show that both types of suppression when administered independently cause reductions in humoral immune responsiveness. However, when both suppressive methods were administered simultaneously a level of suppression occurred which was not greater than that caused by either method alone. Additionally, when ACTH-induced non-specific immunosuppression was established in donors, passive transfers of sera from these donors did not cause suppression in the recipients."} {"id": "PMID:180506", "title": "The effect of grain component of the diet on the response of turkey poults to vitamin D3 and penicillin.", "content": "Three experiments were conducted with turkey poults to study the effects of the grain component of the diet (corn or rye), added fat, penicillin or extra vitamin D on growth and bone ash. In the first trial, where rye replaced corn in the diet, growth was depressed and the pults were rachitic before two weeks of age. Adding fat or penicillin to the rye containing diets significantly improved growth and increased bone ash. In the second trial, adding extra vitamin D3 or penicillin to a diet with rye increased both growth and bone ash. Diets containing either corn or rye were used in the third trial and the results again showed that extra vitamin D or penicillin markedly improved growth and bone ash when added to the diets with rye but did not significantly increase growth of poults on the diets with corn. Bone ash of turkeys fed the corn diets was significantly increased by a combination of extra vitamin D3 and penicillin.", "contents": "The effect of grain component of the diet on the response of turkey poults to vitamin D3 and penicillin. Three experiments were conducted with turkey poults to study the effects of the grain component of the diet (corn or rye), added fat, penicillin or extra vitamin D on growth and bone ash. In the first trial, where rye replaced corn in the diet, growth was depressed and the pults were rachitic before two weeks of age. Adding fat or penicillin to the rye containing diets significantly improved growth and increased bone ash. In the second trial, adding extra vitamin D3 or penicillin to a diet with rye increased both growth and bone ash. Diets containing either corn or rye were used in the third trial and the results again showed that extra vitamin D or penicillin markedly improved growth and bone ash when added to the diets with rye but did not significantly increase growth of poults on the diets with corn. Bone ash of turkeys fed the corn diets was significantly increased by a combination of extra vitamin D3 and penicillin."} {"id": "PMID:180507", "title": "A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 2. Uptake, distribution, and excretion of potassium perchlorate.", "content": "The concentrations of 36Cl-labeled potassium perchlorate (K36CiO4) and previously reported iodide (131I) in the ova, thyroid gland, and blood of the laying hen were compared in this investigation. Radioperchlorate concentration and deposition properties showed a remarkable resemblance to those of iodide (131I). The topographic distribution of radioperchlorate in ova followed a peripheral and concentric ring deposition identical to that observed in the 131I investigation. The studies of the distribution of radioperchlorate showed that about 10.3, 2.0, and 1.4% of a single intramuscular injection of K36CiO4 was retained in the body at 3, 24, and 48 hours, respectively. The largest total concentration in the 3-hour group was found in the blood (2.9%), followed by muscles (2.4%), internal organs (1.1%), and the 10 largest ova (1.0%). The 24 and 48-hour hens' ova showed the largest concentrations with values of 1.5 and 1.2% of the dose, respectively. This represented 76.9 and 81.3% of the total activity retained in the body at these times. The excreta in the 3 and 24-hour experiments accounted for most of the radioperchlorate dose.", "contents": "A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 2. Uptake, distribution, and excretion of potassium perchlorate. The concentrations of 36Cl-labeled potassium perchlorate (K36CiO4) and previously reported iodide (131I) in the ova, thyroid gland, and blood of the laying hen were compared in this investigation. Radioperchlorate concentration and deposition properties showed a remarkable resemblance to those of iodide (131I). The topographic distribution of radioperchlorate in ova followed a peripheral and concentric ring deposition identical to that observed in the 131I investigation. The studies of the distribution of radioperchlorate showed that about 10.3, 2.0, and 1.4% of a single intramuscular injection of K36CiO4 was retained in the body at 3, 24, and 48 hours, respectively. The largest total concentration in the 3-hour group was found in the blood (2.9%), followed by muscles (2.4%), internal organs (1.1%), and the 10 largest ova (1.0%). The 24 and 48-hour hens' ova showed the largest concentrations with values of 1.5 and 1.2% of the dose, respectively. This represented 76.9 and 81.3% of the total activity retained in the body at these times. The excreta in the 3 and 24-hour experiments accounted for most of the radioperchlorate dose."} {"id": "PMID:180508", "title": "Calcium-binding protein and calcium absorption in the laying quail (Coturnix coturnix japonica).", "content": "A vitamin D3-dependent calcium-binding protein (CaBP) has been found in the intestinal mucosa of Japanese quail (Coturnix coturnix japonica). This protein is similar, if not identical to that of the chick (Gallus domesticus). A similar protein fraction appears also in uterine mucosa of laying quail. Both intestinal and uterine CaBP levels are higher in laying than in non-laying quails. Uterine CaBP was higher during egg shell formation than during uterine inactivity. The slight corresponding difference in the intestinal CaBP was not significant. Intestinal calcium absorption measured with 91Y as a reference substance was higher in birds during formation of egg shell than in those with inactive uteri. The possible role of CaBP in calcium translocation is discussed.", "contents": "Calcium-binding protein and calcium absorption in the laying quail (Coturnix coturnix japonica). A vitamin D3-dependent calcium-binding protein (CaBP) has been found in the intestinal mucosa of Japanese quail (Coturnix coturnix japonica). This protein is similar, if not identical to that of the chick (Gallus domesticus). A similar protein fraction appears also in uterine mucosa of laying quail. Both intestinal and uterine CaBP levels are higher in laying than in non-laying quails. Uterine CaBP was higher during egg shell formation than during uterine inactivity. The slight corresponding difference in the intestinal CaBP was not significant. Intestinal calcium absorption measured with 91Y as a reference substance was higher in birds during formation of egg shell than in those with inactive uteri. The possible role of CaBP in calcium translocation is discussed."} {"id": "PMID:180509", "title": "The interaction between Mycobacterium bovis (BCG) and genotype of chicken in increasing the percentage of regression of Rous sarcomas.", "content": "Four breeding groups of chickens were inoculated in the wing-web with Rous sarcoma virus at 8 weeks of age. Treated birds were given a single dose of live organisms of a mile strain of Mycobacterium bovis of variety Calmette Guerin (BCG) as a subcutaneous inoculation adjacent to the emerging tumor. Control birds received no BCG. The breeding groups of chickens included a line selected for ability to cause a high percentage of spontaneous regression of tumors, a susceptible line with a very low level of regression of tumors, and the two reciprocal crosses between these lines. Treatment with BCG greatly enhanced the percentage of regression in the line selected for regression and in the two reciprocal crosses, but was ineffective in the low regression line. Bursectomy of chicks from the low regression line did not permit BCG treatment to increase regression of Rous sarcomas.", "contents": "The interaction between Mycobacterium bovis (BCG) and genotype of chicken in increasing the percentage of regression of Rous sarcomas. Four breeding groups of chickens were inoculated in the wing-web with Rous sarcoma virus at 8 weeks of age. Treated birds were given a single dose of live organisms of a mile strain of Mycobacterium bovis of variety Calmette Guerin (BCG) as a subcutaneous inoculation adjacent to the emerging tumor. Control birds received no BCG. The breeding groups of chickens included a line selected for ability to cause a high percentage of spontaneous regression of tumors, a susceptible line with a very low level of regression of tumors, and the two reciprocal crosses between these lines. Treatment with BCG greatly enhanced the percentage of regression in the line selected for regression and in the two reciprocal crosses, but was ineffective in the low regression line. Bursectomy of chicks from the low regression line did not permit BCG treatment to increase regression of Rous sarcomas."} {"id": "PMID:180510", "title": "Detection of cellular immunity to rous tumors of chickens by the leukocyte migration inhibition reaction.", "content": "Peripheral blood leukocytes obtained from Rous sarcoma-bearing chickens were tested for their ability to be inhibited from migrating in vitro by soluble tumor extract. It was found that the inhibition of leukocytes from chickens with regressing Rous tumors was significantly greater than that of chickens with progressing tumors or non-tumor bearing controls.", "contents": "Detection of cellular immunity to rous tumors of chickens by the leukocyte migration inhibition reaction. Peripheral blood leukocytes obtained from Rous sarcoma-bearing chickens were tested for their ability to be inhibited from migrating in vitro by soluble tumor extract. It was found that the inhibition of leukocytes from chickens with regressing Rous tumors was significantly greater than that of chickens with progressing tumors or non-tumor bearing controls."} {"id": "PMID:180511", "title": "The effect of non-protein energy sources on the ability of the chick to synthesize glucose-6-phosphatase.", "content": "Two experiments were conducted to investigate the relationship of energy source, age and glucose-6-phosphatase activity in the chick. In the first experiment liver glycogen and glucose-6-phosphatase were assayed in chicks of four age groups being fed either a high-fat or high-carbohydrate diet. It was observed that the feeding of the high-fat diet resulted in higher glucose-6-phosphatase activity and lower glycogen levels than did the feeding of the carbohydrate diet. Age was found to significantly influence enzyme activity. Both glucose-6-phosphatase and liver glycogen were found to be negatively correlated in the fat fed chicks. In the second experiment chicks were fed either a high-fat or high-carbohydrate diet for 28 days. Liver glucose-6-phosphatase activity was determined in representative samples of chicks from each group to establish basal levels. The diets were then reversed for a three-day period, after which the chicks were returned to their initial diets. Glucose-6-phosphatase was analysed at each step. Variation in enzyme activity in the chicks initially fed the high-fat diet could be attributed to differences in body weight. However, those chicks originally fed the carbohydrate diet did exhibit a true metabolic adaption when fed the high-fat diet.", "contents": "The effect of non-protein energy sources on the ability of the chick to synthesize glucose-6-phosphatase. Two experiments were conducted to investigate the relationship of energy source, age and glucose-6-phosphatase activity in the chick. In the first experiment liver glycogen and glucose-6-phosphatase were assayed in chicks of four age groups being fed either a high-fat or high-carbohydrate diet. It was observed that the feeding of the high-fat diet resulted in higher glucose-6-phosphatase activity and lower glycogen levels than did the feeding of the carbohydrate diet. Age was found to significantly influence enzyme activity. Both glucose-6-phosphatase and liver glycogen were found to be negatively correlated in the fat fed chicks. In the second experiment chicks were fed either a high-fat or high-carbohydrate diet for 28 days. Liver glucose-6-phosphatase activity was determined in representative samples of chicks from each group to establish basal levels. The diets were then reversed for a three-day period, after which the chicks were returned to their initial diets. Glucose-6-phosphatase was analysed at each step. Variation in enzyme activity in the chicks initially fed the high-fat diet could be attributed to differences in body weight. However, those chicks originally fed the carbohydrate diet did exhibit a true metabolic adaption when fed the high-fat diet."} {"id": "PMID:180512", "title": "Vaccination of chickens against Marek's disease with the turkey herpesvirus vaccine using a pneumatic vaccinator.", "content": "A pneumatic vaccinator has been successfully used to administer cell-associated turkey herpesvirus (HVT) vaccine without a loss in titer due to the pressure required to administer the vaccine. Laboratory studies have also shown that chickens vaccinated with graded doses of the HVT vaccine using doses as low as 41 PFU offered protection against Marek's disease (MD) when compared to the unvaccinated controls. The pneumatic vaccinator has also been successful in administering a combination of HVT vaccine and tissue culture fowl pox vaccine. Vaccinated birds were protected against challenge with virulent MD virus as well as fowl pox virus. Antibiotics such as spectinomycin pentahydrate or lincomycin hydrochloride monohydrate and spectinomycin sulfate tetrahydrate were used in combination with the HVT and fowl pox vaccine and none of the antibiotics appear to have an adverse effect on the efficacy of either vaccine.", "contents": "Vaccination of chickens against Marek's disease with the turkey herpesvirus vaccine using a pneumatic vaccinator. A pneumatic vaccinator has been successfully used to administer cell-associated turkey herpesvirus (HVT) vaccine without a loss in titer due to the pressure required to administer the vaccine. Laboratory studies have also shown that chickens vaccinated with graded doses of the HVT vaccine using doses as low as 41 PFU offered protection against Marek's disease (MD) when compared to the unvaccinated controls. The pneumatic vaccinator has also been successful in administering a combination of HVT vaccine and tissue culture fowl pox vaccine. Vaccinated birds were protected against challenge with virulent MD virus as well as fowl pox virus. Antibiotics such as spectinomycin pentahydrate or lincomycin hydrochloride monohydrate and spectinomycin sulfate tetrahydrate were used in combination with the HVT and fowl pox vaccine and none of the antibiotics appear to have an adverse effect on the efficacy of either vaccine."} {"id": "PMID:180514", "title": "[A change in interneuronal transmission of excitation in the diencephalic regions of the brain under the influence of desoxycorticosterone].", "content": "Experiments were conducted on cats with the aid of electrophysiological methods and the use of blockers of cholino- and adrenoreceptors. It was shown that desoxycorticosterone facilitated the interneuronal transmission of excitation in the diencephalic portions of the brain. This was associated with the excitation under the effect of hormone of M-cholino- and beta-adrenoreceptors of the mediodorsal nucleus of the thalamus present on the postsynaptic membrane.", "contents": "[A change in interneuronal transmission of excitation in the diencephalic regions of the brain under the influence of desoxycorticosterone]. Experiments were conducted on cats with the aid of electrophysiological methods and the use of blockers of cholino- and adrenoreceptors. It was shown that desoxycorticosterone facilitated the interneuronal transmission of excitation in the diencephalic portions of the brain. This was associated with the excitation under the effect of hormone of M-cholino- and beta-adrenoreceptors of the mediodorsal nucleus of the thalamus present on the postsynaptic membrane."} {"id": "PMID:180515", "title": "[The role of adrenaline and ACTH in the process of complex heparin compound formation in the blood during imobilization stress].", "content": "Intensification in immobilization stress of the process of formation of complex heparin compounds in the blood and a corresponding increase in the nonenzymatic fibrinolytic activity was largely determined by the altered hormonal status of theorganism: by adrenaline and ACTH discharge. In the animals with the ACTH secretion blocked by DOCA administration the nonenzymatic fibrinolytic activity in stress remained at the basal level characteristic of the nonstress situation. This activity remained at the basal level also after the block of the alpha-adrenoceptors by phentolaminehydrochloride. Administration of both adrenaline and ACTH considerably intensified in stress the process of formation of heparin complexes; no summation of the action of the exogenous ACTH and adrenaline occurred.", "contents": "[The role of adrenaline and ACTH in the process of complex heparin compound formation in the blood during imobilization stress]. Intensification in immobilization stress of the process of formation of complex heparin compounds in the blood and a corresponding increase in the nonenzymatic fibrinolytic activity was largely determined by the altered hormonal status of theorganism: by adrenaline and ACTH discharge. In the animals with the ACTH secretion blocked by DOCA administration the nonenzymatic fibrinolytic activity in stress remained at the basal level characteristic of the nonstress situation. This activity remained at the basal level also after the block of the alpha-adrenoceptors by phentolaminehydrochloride. Administration of both adrenaline and ACTH considerably intensified in stress the process of formation of heparin complexes; no summation of the action of the exogenous ACTH and adrenaline occurred."} {"id": "PMID:180517", "title": "[Autoregulation of hormonogenesis in the adrenal cortex].", "content": "Experiments were conducted on 60 rats. An attempt was made to ascertain with the aid of histochemical methods the possibility of a direct action of glucocorticoids on the adrenal glands. Incomplete coincidence of histochemical changes following hypophysectomy with the changes caused by the action of cortisone for the same period (10 days), and also a distinct depression with cortisone of histochemical shifts characteristic of the action of ACTH in hypophysectomized animals pointed to the direct (not mediated through the hypophysis) influence of cortisone on the adrenal cortex.", "contents": "[Autoregulation of hormonogenesis in the adrenal cortex]. Experiments were conducted on 60 rats. An attempt was made to ascertain with the aid of histochemical methods the possibility of a direct action of glucocorticoids on the adrenal glands. Incomplete coincidence of histochemical changes following hypophysectomy with the changes caused by the action of cortisone for the same period (10 days), and also a distinct depression with cortisone of histochemical shifts characteristic of the action of ACTH in hypophysectomized animals pointed to the direct (not mediated through the hypophysis) influence of cortisone on the adrenal cortex."} {"id": "PMID:180516", "title": "[Mechanisms of seasonal changes in the circadian corticosteroid function of rats].", "content": "Data are presented concerning seasonal changes in the circadian 11-OCS rhythm in the adrenal glands in the plasma of rats. For the purpose of studying the mechanisms of control of circadian 11-OCS rhythms during the spring and autumn seasons there were studied circadian corticosteroid reactions to ACTH and stress. The \"Cosinor\" method of study was used for analysis of the real circadian rhythm. The data obtained permit to suppose that in autumn the rhythm of the adrenal glands was associated with the circadian rhythm of the central links of the hypothalamo-hypophyseo-adrenal system, and during the spring season an important contribution in the formation of the circadian rhythm of the adrenocortical activity was brought by the adrenal mechanisms.", "contents": "[Mechanisms of seasonal changes in the circadian corticosteroid function of rats]. Data are presented concerning seasonal changes in the circadian 11-OCS rhythm in the adrenal glands in the plasma of rats. For the purpose of studying the mechanisms of control of circadian 11-OCS rhythms during the spring and autumn seasons there were studied circadian corticosteroid reactions to ACTH and stress. The \"Cosinor\" method of study was used for analysis of the real circadian rhythm. The data obtained permit to suppose that in autumn the rhythm of the adrenal glands was associated with the circadian rhythm of the central links of the hypothalamo-hypophyseo-adrenal system, and during the spring season an important contribution in the formation of the circadian rhythm of the adrenocortical activity was brought by the adrenal mechanisms."} {"id": "PMID:180521", "title": "The influence of parathyroid hormone and calcitonin on plasma levels of adenosine 3'5' monophosphate and electrolytes in normal and anephric subjects.", "content": "The purpose of this study was to estimate whether target tissues other than the kidney are responsive to parathyroid hormone (PTH) and calcitonin (CT) in anephric man. Twenty subjects were studied: 12 normal, 4 anephric, 4 anuric ('anephric') individuals. PTH infused into 6 normal subjects produced several fold increase in plasma level of cAMP, whereas CT caused minimal increase in the same number of normal individuals. In 4 anephrics PTH infusion resulted in a delayed rise of plasma cAMP. CT administration to 4 'anephrics' did not change plasma cAMP. In all subjects PTH and CT failed to modify plasma electrolytes level. The data indicate that the kidneys are the main source of cAMP after PTH administration and in anephric subjects extrarenal tissues are the source of circulating cAMP.", "contents": "The influence of parathyroid hormone and calcitonin on plasma levels of adenosine 3'5' monophosphate and electrolytes in normal and anephric subjects. The purpose of this study was to estimate whether target tissues other than the kidney are responsive to parathyroid hormone (PTH) and calcitonin (CT) in anephric man. Twenty subjects were studied: 12 normal, 4 anephric, 4 anuric ('anephric') individuals. PTH infused into 6 normal subjects produced several fold increase in plasma level of cAMP, whereas CT caused minimal increase in the same number of normal individuals. In 4 anephrics PTH infusion resulted in a delayed rise of plasma cAMP. CT administration to 4 'anephrics' did not change plasma cAMP. In all subjects PTH and CT failed to modify plasma electrolytes level. The data indicate that the kidneys are the main source of cAMP after PTH administration and in anephric subjects extrarenal tissues are the source of circulating cAMP."} {"id": "PMID:180518", "title": "[Conversion of proinsulin into insulin in insulin producing tumors in man].", "content": "The enzymatic activity of tissues of insulomas and also the proinsulin and insulin content in them was studied. As revealed, insulomas contained an increased amount of proinsulin in comparison with the unaffected islands of Langerhans. The tumours under study also differed by the capacity to catalyze the splitting of hippuryl-L-arginine, synthetic substrate of carboxypeptidase B. Proinsulin content in the tumours of the islar tissue depended on the presence in them of an enzyme catalyzing the splitting of the substrate at pH 6.8--7.2, this pointing to its participation in the conversion of proinsulin into insulin.", "contents": "[Conversion of proinsulin into insulin in insulin producing tumors in man]. The enzymatic activity of tissues of insulomas and also the proinsulin and insulin content in them was studied. As revealed, insulomas contained an increased amount of proinsulin in comparison with the unaffected islands of Langerhans. The tumours under study also differed by the capacity to catalyze the splitting of hippuryl-L-arginine, synthetic substrate of carboxypeptidase B. Proinsulin content in the tumours of the islar tissue depended on the presence in them of an enzyme catalyzing the splitting of the substrate at pH 6.8--7.2, this pointing to its participation in the conversion of proinsulin into insulin."} {"id": "PMID:180522", "title": "The influence of potassium and ACTH on plasma-aldosterone regulation in anephric patients.", "content": "After increasing the intracellular potassium concentration of seven anephric patients without changing the total body potassium, by administration of insulin-glucose, the plasma-aldosterone concentration increased significantly to 180 percent of the pre-infusion value despite a drop in plasma potassium. A significant correlation between the decrease in the plasma potassium and the increase in plasma aldosterone concentration was found. Plasma cortisol remained unaffected. ACTH stimulation of five anephric patients resulted in a significant simultaneous increase in plasma aldosterone as well as in plasma cortisol. These studies indicate that changes in the intracellular potassium concentration, as well as ACTH stimulation, are important regulators of the aldosterone secretion in anephric patients.", "contents": "The influence of potassium and ACTH on plasma-aldosterone regulation in anephric patients. After increasing the intracellular potassium concentration of seven anephric patients without changing the total body potassium, by administration of insulin-glucose, the plasma-aldosterone concentration increased significantly to 180 percent of the pre-infusion value despite a drop in plasma potassium. A significant correlation between the decrease in the plasma potassium and the increase in plasma aldosterone concentration was found. Plasma cortisol remained unaffected. ACTH stimulation of five anephric patients resulted in a significant simultaneous increase in plasma aldosterone as well as in plasma cortisol. These studies indicate that changes in the intracellular potassium concentration, as well as ACTH stimulation, are important regulators of the aldosterone secretion in anephric patients."} {"id": "PMID:180519", "title": "[Blood levels of ACTH and cortisol in patients with Itsenko-Cushing disease treated with chloditan].", "content": "The authors present the results of examination of the content of ACTH and cortizol in the blood of 55 patients with Itsenko-Cushing disease and of 36 healthy persons. Fifty patients were examined repeatedly after a course of chloditan treatment. Plasma ACTH content was determined by the radioimmunological method, and cortizol -- by the competitive binding method with the help of sets. Investigations carried out showed an increase in blood ACTH and cortizol which proved to be most pronounced in patients with a severe form of Itsenko-Cushing disease. A marked reduction of glucocorticoid function of the adrenal glands with an elevation of ACTH secretion occurred after chloditan therapy. At remote periods after the chloditan treatment ACTH and cortizol secretion depended on clinical manifestations of the disease. It was shown that examination of blood ACTH and cortizol content could be used as an auxiliary criterion in the diagnosis of Itsenko-Cushing disease, in ascertaining the severity of this disease and in the assessment of the efficacy of the treatment carried out.", "contents": "[Blood levels of ACTH and cortisol in patients with Itsenko-Cushing disease treated with chloditan]. The authors present the results of examination of the content of ACTH and cortizol in the blood of 55 patients with Itsenko-Cushing disease and of 36 healthy persons. Fifty patients were examined repeatedly after a course of chloditan treatment. Plasma ACTH content was determined by the radioimmunological method, and cortizol -- by the competitive binding method with the help of sets. Investigations carried out showed an increase in blood ACTH and cortizol which proved to be most pronounced in patients with a severe form of Itsenko-Cushing disease. A marked reduction of glucocorticoid function of the adrenal glands with an elevation of ACTH secretion occurred after chloditan therapy. At remote periods after the chloditan treatment ACTH and cortizol secretion depended on clinical manifestations of the disease. It was shown that examination of blood ACTH and cortizol content could be used as an auxiliary criterion in the diagnosis of Itsenko-Cushing disease, in ascertaining the severity of this disease and in the assessment of the efficacy of the treatment carried out."} {"id": "PMID:180523", "title": "Serum lipids and lipoproteins in acute renal failure.", "content": "Forty-five patients with various forms and phases of acute renal failure without or with haemodialysis treatment were investigated. The concentration of free fatty acids, triglycerides and total cholesterol in serum were determined and separation of lipoprotein classes on agarose gel was performed. Increase in free fatty acids and triglycerides, decrease in cholesterol concentration in serum characterised the anuric phase. The increase of prebeta fraction, the decrease of alpha and beta lipoprotein fraction were found in the oligoanuric phase. Decrease in triglyceride concentration was observed as a regular effect of haemodialysis. Decrease in prebeta and increase in beta lipoprotein fraction immediately after the termination of haemodialysis occurred. In the polyuric phase of acute renal failure there was significant decrease in free fatty acids and triglycerides and increase in cholesterol concentration in serum simultaneous with improvement of clinical signs. An increase in prebeta and decrease in beta lipoprotein fraction was noted in the convalescence phase, despite and opposite trend of serum triglycerides and cholesterol concentrations.", "contents": "Serum lipids and lipoproteins in acute renal failure. Forty-five patients with various forms and phases of acute renal failure without or with haemodialysis treatment were investigated. The concentration of free fatty acids, triglycerides and total cholesterol in serum were determined and separation of lipoprotein classes on agarose gel was performed. Increase in free fatty acids and triglycerides, decrease in cholesterol concentration in serum characterised the anuric phase. The increase of prebeta fraction, the decrease of alpha and beta lipoprotein fraction were found in the oligoanuric phase. Decrease in triglyceride concentration was observed as a regular effect of haemodialysis. Decrease in prebeta and increase in beta lipoprotein fraction immediately after the termination of haemodialysis occurred. In the polyuric phase of acute renal failure there was significant decrease in free fatty acids and triglycerides and increase in cholesterol concentration in serum simultaneous with improvement of clinical signs. An increase in prebeta and decrease in beta lipoprotein fraction was noted in the convalescence phase, despite and opposite trend of serum triglycerides and cholesterol concentrations."} {"id": "PMID:180524", "title": "Lipid patterns in haemodialysed and transplanted patients.", "content": "The plasma lipid pattern was investigated in 103 dialysis patients and 66 renal transplant patients. Only 32 percent of dialysed patients and 30 percent of transplanted patients had a normal lipid pattern. In other patients the most frequent disorder with hypertriglyceridaemia, and less frequently combined or isolated hypercholesterolaemia. Since these lipid abnormalities are known to predispose to an accelerated atherosclerosis, a dietetic therapeutic approach was tried. Fifteen transplanted patients with severe hypertriglyceridaemia were submitted to a hypocaloric (1700 kcal) and low carbohydrate (130 g) diet. During dieting the plasma lipid pattern was normalised and maintained in a normal range for the period of observation (3-12 months).", "contents": "Lipid patterns in haemodialysed and transplanted patients. The plasma lipid pattern was investigated in 103 dialysis patients and 66 renal transplant patients. Only 32 percent of dialysed patients and 30 percent of transplanted patients had a normal lipid pattern. In other patients the most frequent disorder with hypertriglyceridaemia, and less frequently combined or isolated hypercholesterolaemia. Since these lipid abnormalities are known to predispose to an accelerated atherosclerosis, a dietetic therapeutic approach was tried. Fifteen transplanted patients with severe hypertriglyceridaemia were submitted to a hypocaloric (1700 kcal) and low carbohydrate (130 g) diet. During dieting the plasma lipid pattern was normalised and maintained in a normal range for the period of observation (3-12 months)."} {"id": "PMID:180520", "title": "[The effect of ACTH and chorionic gonadotropin on cyclic 3',5'-adenosine monophosphate concentration and of a homogenate of fetal hypophysis on adrenal steroidogenesis in human embryos and fetuses from the 7th to the 12th week of embryonic development].", "content": "It was shown that homogenates of the hypophysis of human fetuses from the 8th to the 12th week of gestation stimulated in vitro formation of F and DEA-sulfate in the adrenal glands of fetuses of the same gestation period. ACTH increased the cAMP concentration in the adrenal glands of all the embryos and fetuses under study; this pointed to the presence in them of ACTH-dependent adenylcyclase, and, consequently, of the ACTH receptors. On the contrary, chorionic hormone produced no effect on the cAMP concentration in the adrenal glands. The data obtained, together with those published earlier suggested that adrenal glands of human fetuses from the 8th week of gestation were already under the controlling influence of ACTH of their hypophyses and that the action mechanism of ACTH on the adrenal glands of fetuses was analogous to its action on the adrenal glands of adult.", "contents": "[The effect of ACTH and chorionic gonadotropin on cyclic 3',5'-adenosine monophosphate concentration and of a homogenate of fetal hypophysis on adrenal steroidogenesis in human embryos and fetuses from the 7th to the 12th week of embryonic development]. It was shown that homogenates of the hypophysis of human fetuses from the 8th to the 12th week of gestation stimulated in vitro formation of F and DEA-sulfate in the adrenal glands of fetuses of the same gestation period. ACTH increased the cAMP concentration in the adrenal glands of all the embryos and fetuses under study; this pointed to the presence in them of ACTH-dependent adenylcyclase, and, consequently, of the ACTH receptors. On the contrary, chorionic hormone produced no effect on the cAMP concentration in the adrenal glands. The data obtained, together with those published earlier suggested that adrenal glands of human fetuses from the 8th week of gestation were already under the controlling influence of ACTH of their hypophyses and that the action mechanism of ACTH on the adrenal glands of fetuses was analogous to its action on the adrenal glands of adult."} {"id": "PMID:180525", "title": "Poliovirus-induced inhibition of polypeptide initiation in vitro on native polyribosomes.", "content": "The inhibition of HeLa cell protein synthesis by poliovirus was studied by examining initiation in vitro on endogenous host polyribosomes. At an early stage, before major viral RNA replication and protein synthesis begins, the initiation of translation on cellular mRNA is strongly inhibited. Fractionation of extracts from infected cells shows that the lesion is associated mainly with the crude polyribosome fraction. The cellular mRNA appears unchanged and is as active as mRNA from control cells in stimulating incorporation. The native ribosomal subunits and KCl-washed polyribosomes from the infected cells are also active. Only the ribosomal wash fraction prepared from the inhibited polyribosomes had reduced activity. However, the reduction in the ribosomal wash activity measured in a reconstructed system is not as large as the inhibition seen with \"native\" polyribosomes. The results indicate that a viral induced inhibition is probably associated with the ribosomal wash fraction, but the reconstructed system is not equivalent to the \"native\" inhibited system.", "contents": "Poliovirus-induced inhibition of polypeptide initiation in vitro on native polyribosomes. The inhibition of HeLa cell protein synthesis by poliovirus was studied by examining initiation in vitro on endogenous host polyribosomes. At an early stage, before major viral RNA replication and protein synthesis begins, the initiation of translation on cellular mRNA is strongly inhibited. Fractionation of extracts from infected cells shows that the lesion is associated mainly with the crude polyribosome fraction. The cellular mRNA appears unchanged and is as active as mRNA from control cells in stimulating incorporation. The native ribosomal subunits and KCl-washed polyribosomes from the infected cells are also active. Only the ribosomal wash fraction prepared from the inhibited polyribosomes had reduced activity. However, the reduction in the ribosomal wash activity measured in a reconstructed system is not as large as the inhibition seen with \"native\" polyribosomes. The results indicate that a viral induced inhibition is probably associated with the ribosomal wash fraction, but the reconstructed system is not equivalent to the \"native\" inhibited system."} {"id": "PMID:180526", "title": "Structure of the prosthetic group of Klebsiella aerogenes citrate (pro-3S)-lyase.", "content": "The prosthetic group of citrate (pro-3S)-lyase [citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetate); EC 4.1.3.6] from Klebsiella aerogenes was obtained by mild alkaline hydrolysis of the enzyme and purified by DEAE-cellulose chromatography. Several chemical and enzymatic degradation products of the compound have been isolated, and analyses of these have shown the structure of the prosthetic group to be 3'(or 2') leads to 1 inch-(5 inches-phosphoribosyl) dephosphocoenzyme A. Proof as to the exact linkage between the two ribose moieties and the anomeric configuration of the glycosidic bonds has not yet been obtained. A similar analysis was obtained for a product isolated after Pronase digestion of the enzyme (without alkaline hydrolysis). The isolated prosthetic group also can serve as a substrate for a crude preparation of acetate:-SH-(acyl carrier protein) enzyme ligase (AMP) from K. aerogenes, pure pig heart citrate (si)-synthase (EC 4.1.3.7), and pure rat liver ATP citrate (pro-3S)-lyase (EC4.1.3.8). This compound is the first shown to substitute for coenzyme A in the latter reaction.", "contents": "Structure of the prosthetic group of Klebsiella aerogenes citrate (pro-3S)-lyase. The prosthetic group of citrate (pro-3S)-lyase [citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetate); EC 4.1.3.6] from Klebsiella aerogenes was obtained by mild alkaline hydrolysis of the enzyme and purified by DEAE-cellulose chromatography. Several chemical and enzymatic degradation products of the compound have been isolated, and analyses of these have shown the structure of the prosthetic group to be 3'(or 2') leads to 1 inch-(5 inches-phosphoribosyl) dephosphocoenzyme A. Proof as to the exact linkage between the two ribose moieties and the anomeric configuration of the glycosidic bonds has not yet been obtained. A similar analysis was obtained for a product isolated after Pronase digestion of the enzyme (without alkaline hydrolysis). The isolated prosthetic group also can serve as a substrate for a crude preparation of acetate:-SH-(acyl carrier protein) enzyme ligase (AMP) from K. aerogenes, pure pig heart citrate (si)-synthase (EC 4.1.3.7), and pure rat liver ATP citrate (pro-3S)-lyase (EC4.1.3.8). This compound is the first shown to substitute for coenzyme A in the latter reaction."} {"id": "PMID:180527", "title": "Sodium-stimulated alpha-aminoisobutyric acid transport by membrane vesicles from simian virus-transformed mouse cells.", "content": "Uptake of alpha-aminoisobutyric acid, by membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by simian virus 40, is stimulated by sodium chloride. Both in the presence and absence of Na+ uptake is time-dependent and osmotically sensitive. The Na+-stimulated uptake is inhibited by other amino acids. The kinetics of transport of alpha-aminoisobutyric acid are shown to be biphasic both in whole cells and in the membrane vesicles. Only the high affinity system is stimulated by sodium in the membrane vesicles. These results demonstrate that observations made on living cells correlate with observations made on isolated membrane vesicles, and indicate that these membrane vesicles have retained the cellular amino acid transport system functionally intact.", "contents": "Sodium-stimulated alpha-aminoisobutyric acid transport by membrane vesicles from simian virus-transformed mouse cells. Uptake of alpha-aminoisobutyric acid, by membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by simian virus 40, is stimulated by sodium chloride. Both in the presence and absence of Na+ uptake is time-dependent and osmotically sensitive. The Na+-stimulated uptake is inhibited by other amino acids. The kinetics of transport of alpha-aminoisobutyric acid are shown to be biphasic both in whole cells and in the membrane vesicles. Only the high affinity system is stimulated by sodium in the membrane vesicles. These results demonstrate that observations made on living cells correlate with observations made on isolated membrane vesicles, and indicate that these membrane vesicles have retained the cellular amino acid transport system functionally intact."} {"id": "PMID:180528", "title": "Affinity label for beta-adrenergic receptor in turkey erythrocytes.", "content": "The compound N-[2-hydroxy-3-(1-naphthoxy)-propyl]-N'-bromoacetylethylenediamine (NHNP-NBE) was found to label covalently the beta-adrenergic receptor in turkey erythrocytes. The compound inhibits irreversibly 1-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the whole turkey erythrocyte as well as in the erythrocyte membranes possessing the beta-receptor. The affinity label blocks, also irreversibly, the specific [3H] propranolol binding, whereas other bromoacetyl compounds tested have no effect on binding, even at high concentrations, which cause enzyme inactivation. 1-Epinephrine and propranolol offer protection against the affinity label in whole turkey erythrocytes as well as in membranes prepared from these cells. The potential usefulness of an irreversible beta-antagonist is discussed.", "contents": "Affinity label for beta-adrenergic receptor in turkey erythrocytes. The compound N-[2-hydroxy-3-(1-naphthoxy)-propyl]-N'-bromoacetylethylenediamine (NHNP-NBE) was found to label covalently the beta-adrenergic receptor in turkey erythrocytes. The compound inhibits irreversibly 1-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the whole turkey erythrocyte as well as in the erythrocyte membranes possessing the beta-receptor. The affinity label blocks, also irreversibly, the specific [3H] propranolol binding, whereas other bromoacetyl compounds tested have no effect on binding, even at high concentrations, which cause enzyme inactivation. 1-Epinephrine and propranolol offer protection against the affinity label in whole turkey erythrocytes as well as in membranes prepared from these cells. The potential usefulness of an irreversible beta-antagonist is discussed."} {"id": "PMID:180529", "title": "Extracytoplasmic adenylate cyclase of Bordetella pertussis.", "content": "Soluble adenylate cyclase [EC 4.6.1.1] accumulates in the culture medium of exponentially growing Bordetella pertussis (300-900 pmol of cAMP formed/min per ml of 24 hr culture supernatant). In addition, there is an extracytoplasmic adenylate cyclase which enables the intact organisms to form [32P] cAMP (adenosine 3':5'-cyclic monophosphate) from exogenous [alpha-32P] ATP (200-1200 nmol of cAMP formed/min per g wet weight of cells) and which comprises 20-45% of the total adenylate cyclase activity. In contrast, only 1.7 and 2.4% of the total cell malate dehydrogenase [EC 1.1.1.37] and alkaline phosphatase [EC 3.1.3.1], respectively, are detectable in the intact cell. Trypsin treatment of intact organisms destroys 96% of the extracytoplasmic adenylate cyclase, but does not reduce the total cell malate dehydrogenase or a small pool of intracellular adenylate cyclase. Four compartments of adenylate cyclase in B. pertussis are proposed; (A) soluble enzyme in the culture supernatant (up to 20% of the total activity); (B) enzyme associated with intact cells and measurable without cell disruption (20-45%); (C) extracytoplasmic enzyme sensitive to trypsin, but not measurable in intact cells at standard substrate concentrations (40-60%); and (D) intracellular enzyme (7-9%). In comparison with previously studied bacterial adenylate cyclases, the extracytoplasmic location appears to be unique to the B. pertussis enzyme.", "contents": "Extracytoplasmic adenylate cyclase of Bordetella pertussis. Soluble adenylate cyclase [EC 4.6.1.1] accumulates in the culture medium of exponentially growing Bordetella pertussis (300-900 pmol of cAMP formed/min per ml of 24 hr culture supernatant). In addition, there is an extracytoplasmic adenylate cyclase which enables the intact organisms to form [32P] cAMP (adenosine 3':5'-cyclic monophosphate) from exogenous [alpha-32P] ATP (200-1200 nmol of cAMP formed/min per g wet weight of cells) and which comprises 20-45% of the total adenylate cyclase activity. In contrast, only 1.7 and 2.4% of the total cell malate dehydrogenase [EC 1.1.1.37] and alkaline phosphatase [EC 3.1.3.1], respectively, are detectable in the intact cell. Trypsin treatment of intact organisms destroys 96% of the extracytoplasmic adenylate cyclase, but does not reduce the total cell malate dehydrogenase or a small pool of intracellular adenylate cyclase. Four compartments of adenylate cyclase in B. pertussis are proposed; (A) soluble enzyme in the culture supernatant (up to 20% of the total activity); (B) enzyme associated with intact cells and measurable without cell disruption (20-45%); (C) extracytoplasmic enzyme sensitive to trypsin, but not measurable in intact cells at standard substrate concentrations (40-60%); and (D) intracellular enzyme (7-9%). In comparison with previously studied bacterial adenylate cyclases, the extracytoplasmic location appears to be unique to the B. pertussis enzyme."} {"id": "PMID:180530", "title": "Regulation of viral transciption and tumor antigen expression in cells transformed by simian virus 40.", "content": "We have studied the expression of simian virus 40 (SV40) specific tumor antigen (T-antigen) and viral RNA in SV40-transformed mouse 3T3 cells that are temperature-sensitive for the expression of the transformed phenotype (ts SV3T3). Although transformed by wild-type SV40, ts SV3T3 cells at 32 degrees behave like standard transformants, while at 39 degrees they became arrested in G1 after reaching saturation density or under conditions of serum starvation. ts SV3T3 cells at 32 degrees or exponentially growing at 39 degrees are uniformly T-antigen positive. However, after G1 arrest at 39 degrees the majority of the cells becomes T-antigen negative. Induction of proliferation in the resting cultures results in the reappearance of T-antigen in most of the cells, concomitant with the induction of DNA synthesis. The reason for the disappearance of T-antigen from ts SV3T3 cells arrested in G1 seems to reside in a transcriptional control operating on the integrated viral DNA, since these cells contain no appreciable amounts of SV40 specific RNA. Viral RNA can be easily detected in cells growint at 32 degrees or at 39 degrees. The results suggest that transcription of the viral genome in SV40-transformed cells is cell-cycle-dependent.", "contents": "Regulation of viral transciption and tumor antigen expression in cells transformed by simian virus 40. We have studied the expression of simian virus 40 (SV40) specific tumor antigen (T-antigen) and viral RNA in SV40-transformed mouse 3T3 cells that are temperature-sensitive for the expression of the transformed phenotype (ts SV3T3). Although transformed by wild-type SV40, ts SV3T3 cells at 32 degrees behave like standard transformants, while at 39 degrees they became arrested in G1 after reaching saturation density or under conditions of serum starvation. ts SV3T3 cells at 32 degrees or exponentially growing at 39 degrees are uniformly T-antigen positive. However, after G1 arrest at 39 degrees the majority of the cells becomes T-antigen negative. Induction of proliferation in the resting cultures results in the reappearance of T-antigen in most of the cells, concomitant with the induction of DNA synthesis. The reason for the disappearance of T-antigen from ts SV3T3 cells arrested in G1 seems to reside in a transcriptional control operating on the integrated viral DNA, since these cells contain no appreciable amounts of SV40 specific RNA. Viral RNA can be easily detected in cells growint at 32 degrees or at 39 degrees. The results suggest that transcription of the viral genome in SV40-transformed cells is cell-cycle-dependent."} {"id": "PMID:180531", "title": "Structure of a nicked DNA-protein complex isolated from simian virus 40: covalent attachment of the protein to DNA and nick specificity.", "content": "A portion of the nicked circular DNA isolated from purified simian virus 40 contains a protein-DNA complex in which protein(s) is covalently attached to the end of a DNA single strand. (Nicked DNA is double-stranded DNA that contains at least one single-strand scission.) The protein was visualized by electron microscopy and labeled in vitro with 125I. The bond between the protein and the DNA is stable in alkali, 4 M guanidine-hydrochloride, 3.86 M hydroxylamine (pH 4,23), and in 98% formamide. Most of the molecules in the nicked circular DNA fraction contained one nick. The nick occurs on either of the two complementary strands; the specific nick sites on the two strands are staggered, but lie within a few hundred nucleotides of each other.", "contents": "Structure of a nicked DNA-protein complex isolated from simian virus 40: covalent attachment of the protein to DNA and nick specificity. A portion of the nicked circular DNA isolated from purified simian virus 40 contains a protein-DNA complex in which protein(s) is covalently attached to the end of a DNA single strand. (Nicked DNA is double-stranded DNA that contains at least one single-strand scission.) The protein was visualized by electron microscopy and labeled in vitro with 125I. The bond between the protein and the DNA is stable in alkali, 4 M guanidine-hydrochloride, 3.86 M hydroxylamine (pH 4,23), and in 98% formamide. Most of the molecules in the nicked circular DNA fraction contained one nick. The nick occurs on either of the two complementary strands; the specific nick sites on the two strands are staggered, but lie within a few hundred nucleotides of each other."} {"id": "PMID:180532", "title": "Acceptor proteins in rat androgenic tissue chromatin.", "content": "Fractionation of chromatin into urea-soluble chromosomal nonhistone proteins (UP), histones (HP), and DNA-associated nonhistone proteins (NP) revealed that the NP fraction from testicular and prostatic chromatin contains organ-specific acceptors for complexes of 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and its receptor. This acceptor capacity of androgenic tissue chromatin could be transferred to chromatins from non-target tissues with the NP fraction of DNA-associated proteins. Phosphorylation of chromatin enhanced its hormone-receptor binding capacity.", "contents": "Acceptor proteins in rat androgenic tissue chromatin. Fractionation of chromatin into urea-soluble chromosomal nonhistone proteins (UP), histones (HP), and DNA-associated nonhistone proteins (NP) revealed that the NP fraction from testicular and prostatic chromatin contains organ-specific acceptors for complexes of 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and its receptor. This acceptor capacity of androgenic tissue chromatin could be transferred to chromatins from non-target tissues with the NP fraction of DNA-associated proteins. Phosphorylation of chromatin enhanced its hormone-receptor binding capacity."} {"id": "PMID:180533", "title": "Phenotypic transformation of clonal myogenic cells to cells resembling chondrocytes.", "content": "The nicotinamide analogue 6-aminonicotinamide and dibutyryl 3':5'-cAMP inhibit myogenesis in a clonal rat cell line from skeletal muscle. Both reagents produce a similar morphological response in the cells, and stimulate collagen and glycosaminoglycan synthesis. These data suggest that 6-aminonicotinamide and dibutyryl cAMP induce a phenotypic transformation of myogenic cells to cells that share many characteristics with chondrocytes.", "contents": "Phenotypic transformation of clonal myogenic cells to cells resembling chondrocytes. The nicotinamide analogue 6-aminonicotinamide and dibutyryl 3':5'-cAMP inhibit myogenesis in a clonal rat cell line from skeletal muscle. Both reagents produce a similar morphological response in the cells, and stimulate collagen and glycosaminoglycan synthesis. These data suggest that 6-aminonicotinamide and dibutyryl cAMP induce a phenotypic transformation of myogenic cells to cells that share many characteristics with chondrocytes."} {"id": "PMID:180534", "title": "Affinity isolation of cultured tumor cells by means of drugs and hormones covalently bound to glass and Sepharose beads.", "content": "Isoproterenol, corticotropin (ACTH), and triodothyronine immobilized on glass and Sepharose beads by diazotization procedures have been shown to interact with cultured tumor cells of \"target tissue\" origin. Cells used were rat glioma cells (C6), rat adrenal tumor cells (Y-1), and rat pituitary tumor cells (GH3). The rat glioma cells bound principally to immobilized isoproterenol, whereas the rat adrenal tumor cells bound to immobilized corticotropin, and rat pituitary tumor cells bound to immobilized triiodothyronine. Binding was inhibited by preincubation of the cells in soluble drug or hormone. With C6 cells there was a positive correlation between adenylate cyclase [ATP pyrophosphate-lyase (cyclizing, EC 4.6.1.1] stimulation and the degree of binding to the immobilized isoproterenol. Norepinephrine, bound through the ethanolamine side chain via an amide linkage, did not bind cells, demonstrating specific structural requirements for drug-cell interactions. HeLa cells were shown to bind tightly to diphtheria toxin coupled to Sepharose beads via an amide bond. This binding was inhibited by prior incubation of the Sepharose toxin with purified antitoxin. Toxin bound to Sepharose via an azo bond did not bind cells. These data suggest that the cell affinities are due to cell surface receptors interacting with the immobilized drugs and hormones, and that the observed affinities possibly reflect the relative receptor complement of these cells.", "contents": "Affinity isolation of cultured tumor cells by means of drugs and hormones covalently bound to glass and Sepharose beads. Isoproterenol, corticotropin (ACTH), and triodothyronine immobilized on glass and Sepharose beads by diazotization procedures have been shown to interact with cultured tumor cells of \"target tissue\" origin. Cells used were rat glioma cells (C6), rat adrenal tumor cells (Y-1), and rat pituitary tumor cells (GH3). The rat glioma cells bound principally to immobilized isoproterenol, whereas the rat adrenal tumor cells bound to immobilized corticotropin, and rat pituitary tumor cells bound to immobilized triiodothyronine. Binding was inhibited by preincubation of the cells in soluble drug or hormone. With C6 cells there was a positive correlation between adenylate cyclase [ATP pyrophosphate-lyase (cyclizing, EC 4.6.1.1] stimulation and the degree of binding to the immobilized isoproterenol. Norepinephrine, bound through the ethanolamine side chain via an amide linkage, did not bind cells, demonstrating specific structural requirements for drug-cell interactions. HeLa cells were shown to bind tightly to diphtheria toxin coupled to Sepharose beads via an amide bond. This binding was inhibited by prior incubation of the Sepharose toxin with purified antitoxin. Toxin bound to Sepharose via an azo bond did not bind cells. These data suggest that the cell affinities are due to cell surface receptors interacting with the immobilized drugs and hormones, and that the observed affinities possibly reflect the relative receptor complement of these cells."} {"id": "PMID:180535", "title": "A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug.", "content": "Purified rat liver peroxisomes contain a cyanide-insensitive fatty acyl-CoA oxidizing system that uses O2 and NAD as electron acceptors. The system was detected by the ability of added palmitoyl-CoA to elicit O2 consumption, H2O2 production, and O2-dependent NAD reduction. The activity of this system is increased approximately one order of magnitude in rats treated with clofibrate, a hypolipidemic drug known to cause peroxisomal proliferation.", "contents": "A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Purified rat liver peroxisomes contain a cyanide-insensitive fatty acyl-CoA oxidizing system that uses O2 and NAD as electron acceptors. The system was detected by the ability of added palmitoyl-CoA to elicit O2 consumption, H2O2 production, and O2-dependent NAD reduction. The activity of this system is increased approximately one order of magnitude in rats treated with clofibrate, a hypolipidemic drug known to cause peroxisomal proliferation."} {"id": "PMID:180536", "title": "Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus.", "content": "The hypothesis that surface modulating assemblies containing microfilaments and microtubules and altered after cellular transformation was tested on cells infected with temperature-sensitive mutants of avian sarcoma virus. Untransformed cells (mouse 3T3 and chick fibroblasts), cells transformed by simian virus 40 (SV 3T3), and chick fibroblasts infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV-A-infected cells) were first compared for differences in microfilament and microtubule patterns after treatment with fluorescein-labeled antibodies to actin and tubulin. Transformed cells showed disappearance of ordered stress microfilaments and thickened or diffuse alterations of microtubular arrays. At restrictive temperatures (41 degrees), chick fibroblasts infected with a temperature-sensitive mutant (ts 68) of Rous sarcoma virus showed normal patterns of stress fialments and radial microtubular arrays originating in 1 or 2 centrioles. At permissive temperatures (37 degrees), these patterns were disordered and resembled those of SR-RSV-A-infected cells. After a shift from 41 degrees to 37 degrees, the changes in microtubules were observed in the majority of cells within 1 hr. These changes were reversible and did not result from the inability of tubulin to polymerize. In ts 68-infected cells at permissive temperatures, concanavalin A induced much less surface modulation (inhibition of receptor mobility) than at restrictive temperatures. These results suggest that cellular transformation alters both the structure and function of surface modulating assemblies and prompt the hypothesis that products of viral transforming genes may affect these assemblies with a consequent loss of growth control.", "contents": "Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus. The hypothesis that surface modulating assemblies containing microfilaments and microtubules and altered after cellular transformation was tested on cells infected with temperature-sensitive mutants of avian sarcoma virus. Untransformed cells (mouse 3T3 and chick fibroblasts), cells transformed by simian virus 40 (SV 3T3), and chick fibroblasts infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV-A-infected cells) were first compared for differences in microfilament and microtubule patterns after treatment with fluorescein-labeled antibodies to actin and tubulin. Transformed cells showed disappearance of ordered stress microfilaments and thickened or diffuse alterations of microtubular arrays. At restrictive temperatures (41 degrees), chick fibroblasts infected with a temperature-sensitive mutant (ts 68) of Rous sarcoma virus showed normal patterns of stress fialments and radial microtubular arrays originating in 1 or 2 centrioles. At permissive temperatures (37 degrees), these patterns were disordered and resembled those of SR-RSV-A-infected cells. After a shift from 41 degrees to 37 degrees, the changes in microtubules were observed in the majority of cells within 1 hr. These changes were reversible and did not result from the inability of tubulin to polymerize. In ts 68-infected cells at permissive temperatures, concanavalin A induced much less surface modulation (inhibition of receptor mobility) than at restrictive temperatures. These results suggest that cellular transformation alters both the structure and function of surface modulating assemblies and prompt the hypothesis that products of viral transforming genes may affect these assemblies with a consequent loss of growth control."} {"id": "PMID:180537", "title": "Release by human chromosome 3 of the block at G1 of the cell cycle, in hybrids between tsAF8 hamster and human cells.", "content": "A temperature-sensitive mutant of Syrian hamster cells, AF8 was fused with simian-virus-40-transformed Lesch-Nyhan fibroblasts; LNSV, in the presence of beta-propiolactone-inactivated Sendai virus. The AF8 cells grow well at 33.5 degrees but are arrested in mid G1 period when shifted to 39 degrees. The LNSV cells are deficient in hypoxanthine guanine phosphoribosyltransferase. The hybrid clones were selected in hypoxanthine-aminopterin-thymidine medium at 39 degrees. A total of 20 clones was isolated and karyotyped. All clones contained most of the hamster chromosomes and one to eight human chromosomes. The preferential retention of human chromosome 3 was observed in 100% of the metaphases of all clones. In nine of the clones, the only human chromosome present was chromosome 3. The results indicate that human chromosome 3 is responsible for conferring to the hybrid cells the ability to grow at nonpermissive temperature for AF8 cells, i.e., the ability to overcome the G1 block. These findings, together with other reports in the cell cycle may be regulated by genes located on different chromosomes.", "contents": "Release by human chromosome 3 of the block at G1 of the cell cycle, in hybrids between tsAF8 hamster and human cells. A temperature-sensitive mutant of Syrian hamster cells, AF8 was fused with simian-virus-40-transformed Lesch-Nyhan fibroblasts; LNSV, in the presence of beta-propiolactone-inactivated Sendai virus. The AF8 cells grow well at 33.5 degrees but are arrested in mid G1 period when shifted to 39 degrees. The LNSV cells are deficient in hypoxanthine guanine phosphoribosyltransferase. The hybrid clones were selected in hypoxanthine-aminopterin-thymidine medium at 39 degrees. A total of 20 clones was isolated and karyotyped. All clones contained most of the hamster chromosomes and one to eight human chromosomes. The preferential retention of human chromosome 3 was observed in 100% of the metaphases of all clones. In nine of the clones, the only human chromosome present was chromosome 3. The results indicate that human chromosome 3 is responsible for conferring to the hybrid cells the ability to grow at nonpermissive temperature for AF8 cells, i.e., the ability to overcome the G1 block. These findings, together with other reports in the cell cycle may be regulated by genes located on different chromosomes."} {"id": "PMID:180538", "title": "Clonal variation in albumin messenger RNA activity in hepatoma cells.", "content": "The clonal variation in rate of albumin synthesis in hepatoma cells is described as a tool for the study of epigenetic control of differentiation. Previous studies have demonstrated that, from a population of hepatome cells, variant subclones can be readily isolated that produce albumin at different rates. Each clonal variant had a characteristic rate of albumin production, and the clones clustered around discrete values that formed a geometric progression. The present experiments, using a cell-free protein-synthesizing system from wheat germ; show that albumin messenger RNA activity is directly proportional to the rate of albumin synthesis in three different hepatoma clones, thus suggesting a pretranslational control of albumin production. Possible hypotheses to explain the geometric pattern of clonal variation are discussed with respect to the organization and control of the transcriptional unit.", "contents": "Clonal variation in albumin messenger RNA activity in hepatoma cells. The clonal variation in rate of albumin synthesis in hepatoma cells is described as a tool for the study of epigenetic control of differentiation. Previous studies have demonstrated that, from a population of hepatome cells, variant subclones can be readily isolated that produce albumin at different rates. Each clonal variant had a characteristic rate of albumin production, and the clones clustered around discrete values that formed a geometric progression. The present experiments, using a cell-free protein-synthesizing system from wheat germ; show that albumin messenger RNA activity is directly proportional to the rate of albumin synthesis in three different hepatoma clones, thus suggesting a pretranslational control of albumin production. Possible hypotheses to explain the geometric pattern of clonal variation are discussed with respect to the organization and control of the transcriptional unit."} {"id": "PMID:180539", "title": "Heredity of the GIX thymocyte antigen associated with murine leukemia virus: segregation data simulating genetic linkage.", "content": "The GIX antigen is a feature of the gp70 envelope glycoprotein of murine luekemia virus (MuLV). This GIX-gp70 molecule is found on the thymocytes of some (GIX+) strains of mice, where its expression is controlled by two mendelian genes, Gv-1 and Gv-2. Previous recombination data involving the prototype GIX+ strain 129 indicated that the H-2 (chromosome 17) and Gv-1 loci are linked, at a distance of 36 units from one another. New data indicate that the association of H-2 and GIX phenotypes is an example of quasi-linkage, evidently dependent in this instance on heterozygosity at a locus or loci in the vicinity of H-2. Other previous recombination data, involving the GIX+ strain AKR, had indicated that the Gpd-1 (chromosome 4) and Gv-1 loci are linked at a distance of 19 units from one another. New data from other crosses show that this association of Gpd-1 (glucose-6-phosphate dehydrogenase 1) and GIX phenotypes also constitutes quasi-linkage, evidently due to heterozygosity at the Fv-1 locus. An important theoretical consequence of quasi-linkage in general is that it should enhance the heritability of particular constellations of unlinked genes, and so influence population structure. Our new data are discussed from the viewpoint that MuLV genomes are apparently concerned in quasi-linkage, and therefore by the same arguments may influence the genetic structure of populations. This in turn may strengthen the view that integrated MuLV genomes are not simply intruded into a self-sufficient cellular genome, but are themselves elements of the cellular genome with primary functions, perhaps in reproduction or embryogenesis.", "contents": "Heredity of the GIX thymocyte antigen associated with murine leukemia virus: segregation data simulating genetic linkage. The GIX antigen is a feature of the gp70 envelope glycoprotein of murine luekemia virus (MuLV). This GIX-gp70 molecule is found on the thymocytes of some (GIX+) strains of mice, where its expression is controlled by two mendelian genes, Gv-1 and Gv-2. Previous recombination data involving the prototype GIX+ strain 129 indicated that the H-2 (chromosome 17) and Gv-1 loci are linked, at a distance of 36 units from one another. New data indicate that the association of H-2 and GIX phenotypes is an example of quasi-linkage, evidently dependent in this instance on heterozygosity at a locus or loci in the vicinity of H-2. Other previous recombination data, involving the GIX+ strain AKR, had indicated that the Gpd-1 (chromosome 4) and Gv-1 loci are linked at a distance of 19 units from one another. New data from other crosses show that this association of Gpd-1 (glucose-6-phosphate dehydrogenase 1) and GIX phenotypes also constitutes quasi-linkage, evidently due to heterozygosity at the Fv-1 locus. An important theoretical consequence of quasi-linkage in general is that it should enhance the heritability of particular constellations of unlinked genes, and so influence population structure. Our new data are discussed from the viewpoint that MuLV genomes are apparently concerned in quasi-linkage, and therefore by the same arguments may influence the genetic structure of populations. This in turn may strengthen the view that integrated MuLV genomes are not simply intruded into a self-sufficient cellular genome, but are themselves elements of the cellular genome with primary functions, perhaps in reproduction or embryogenesis."} {"id": "PMID:180541", "title": "Ammonium sulfate activation of phosphodiesterase in homogenates of larvae of the european corn borer.", "content": "European corn borer phosphodiesterase is highly activated by (NH4)2SO4 and moderately activated by NH4C1 (pH 7.6, 33 degrees). Vertebrate and crayfish diesterases, on the other hand, are inhibited by (NH4)2SO4. It is likely that (NH4)2SO4 causes some configurational change in the European corn borer phosphodiesterase molecule which results in the exposure of more active sites and hence greater enzyme activity. In in vitro tests caffeine (0.008 M) and theophylline (0.008 M) inhibit phosphodiesterase more effectively in European corn borer larvae than in crayfish, ovine, bovine, or rat tissue.", "contents": "Ammonium sulfate activation of phosphodiesterase in homogenates of larvae of the european corn borer. European corn borer phosphodiesterase is highly activated by (NH4)2SO4 and moderately activated by NH4C1 (pH 7.6, 33 degrees). Vertebrate and crayfish diesterases, on the other hand, are inhibited by (NH4)2SO4. It is likely that (NH4)2SO4 causes some configurational change in the European corn borer phosphodiesterase molecule which results in the exposure of more active sites and hence greater enzyme activity. In in vitro tests caffeine (0.008 M) and theophylline (0.008 M) inhibit phosphodiesterase more effectively in European corn borer larvae than in crayfish, ovine, bovine, or rat tissue."} {"id": "PMID:180542", "title": "Effect of adenosine 3',5'-monophosphate on serine metabolism in chick tissues.", "content": "The effect of cyclic 3',5'-AMP and supplemental dietary glycine upon de novo synthesis of serine metabolic enzymes in chick livers were examined. Chicks fed crystalline amino acid diets containing 2% glycine had approximately twofold the activity in liver for 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase compared to liver tissue from chicks fed diets lacking in dietary glycine. Chicks subjected to daily intraperitoneal injections of cyclic 3',5'-AMP and fed diets containing no dietary glycine contained biosynthetic enzyme activity similar to glycine-fed chicks suggesting a correlation between glycine and cyclic AMP for serine enzyme induction. The elevated enzyme activity in liver of chicks fed dietary glycine or injected with cyclic AMP was inhibited when chicks were also injected with actinomycin D indicating de novo synthesis of 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase. Dietary glycine or cyclic AMP, however, did not change serine dehydratase and glycerate dehydrogenase activities in chick liver.", "contents": "Effect of adenosine 3',5'-monophosphate on serine metabolism in chick tissues. The effect of cyclic 3',5'-AMP and supplemental dietary glycine upon de novo synthesis of serine metabolic enzymes in chick livers were examined. Chicks fed crystalline amino acid diets containing 2% glycine had approximately twofold the activity in liver for 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase compared to liver tissue from chicks fed diets lacking in dietary glycine. Chicks subjected to daily intraperitoneal injections of cyclic 3',5'-AMP and fed diets containing no dietary glycine contained biosynthetic enzyme activity similar to glycine-fed chicks suggesting a correlation between glycine and cyclic AMP for serine enzyme induction. The elevated enzyme activity in liver of chicks fed dietary glycine or injected with cyclic AMP was inhibited when chicks were also injected with actinomycin D indicating de novo synthesis of 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase. Dietary glycine or cyclic AMP, however, did not change serine dehydratase and glycerate dehydrogenase activities in chick liver."} {"id": "PMID:180543", "title": "Studies on rats with islet beta cell tumors induced by nicotinamide and streptozotocin.", "content": "Islet beta cell adenomata were induced in rats by combined treatment with nicotinamide and streptozotocin. Three weeks after treatment marked alterations in glucose tolerance were noted in animals which later exhibited large beta cell tumors. Eight months after treatment, the rats known to have beta cell tumors on the basis of marked hypoglycemia and later confirmed by autopsy showed variable response to a glucose load. Some tumor-bearing rats showed fast response to glucose load, their blood sugar levels were elevated moderately and returned to normal or below normal levels rapidly; these animals are described as having \"fast-acting tumors\". Rats with \"slow-acting tumors\" responded sluggishly to a glucose load; their blood glucose pattern was similar to that of subdiabetic animals. Animals with beta cell tumors exhibited elevated serum insulin levels 30 min after glucose administration. Insulin biosynthesis by beta cell adenomata was demonstrated by in vitro incorporation of [14C]leucine into proinsulin and insulin. In the small number of tumor samples studied, a stimulatory effect of glucose on insulin biosynthesis was observed.", "contents": "Studies on rats with islet beta cell tumors induced by nicotinamide and streptozotocin. Islet beta cell adenomata were induced in rats by combined treatment with nicotinamide and streptozotocin. Three weeks after treatment marked alterations in glucose tolerance were noted in animals which later exhibited large beta cell tumors. Eight months after treatment, the rats known to have beta cell tumors on the basis of marked hypoglycemia and later confirmed by autopsy showed variable response to a glucose load. Some tumor-bearing rats showed fast response to glucose load, their blood sugar levels were elevated moderately and returned to normal or below normal levels rapidly; these animals are described as having \"fast-acting tumors\". Rats with \"slow-acting tumors\" responded sluggishly to a glucose load; their blood glucose pattern was similar to that of subdiabetic animals. Animals with beta cell tumors exhibited elevated serum insulin levels 30 min after glucose administration. Insulin biosynthesis by beta cell adenomata was demonstrated by in vitro incorporation of [14C]leucine into proinsulin and insulin. In the small number of tumor samples studied, a stimulatory effect of glucose on insulin biosynthesis was observed."} {"id": "PMID:180544", "title": "Brain amines and spontaneous epileptic seizures in the Mongolian gerbil.", "content": "The seizure sensitive (WJL)UC) strain of Mongolian gerbils has been used to investigate the effects of drugs that modify central monoamine activity on spontaneous epileptiform seizures. Increasing central norepinephrine and dopamine levels significantly reduced the severity of the seizures and the importance of dopamine was further demonstrated by the protection from seizures after administration of the dopaminergic agonist apomorphine. These data indicate that a search for differences in regional levels, or turnover rates, of these amines between seizure sensitive and seizure resistant strains of gerbils might be profitable in determining the genetic deficit underlying the seizure phenomenon in these animals.", "contents": "Brain amines and spontaneous epileptic seizures in the Mongolian gerbil. The seizure sensitive (WJL)UC) strain of Mongolian gerbils has been used to investigate the effects of drugs that modify central monoamine activity on spontaneous epileptiform seizures. Increasing central norepinephrine and dopamine levels significantly reduced the severity of the seizures and the importance of dopamine was further demonstrated by the protection from seizures after administration of the dopaminergic agonist apomorphine. These data indicate that a search for differences in regional levels, or turnover rates, of these amines between seizure sensitive and seizure resistant strains of gerbils might be profitable in determining the genetic deficit underlying the seizure phenomenon in these animals."} {"id": "PMID:180545", "title": "The effect of ACTH-analogues on motor behavior and visual evoked responses in rats.", "content": "Averaged visual evoked responses (VER) in cortical area 17 were recorded one hour after the administration of 7-l-phe ACTH4-10 or 7-d-phe ACTH4-10 to artificially ventilated rats, paralysed with gallamine. In addition, the effects of these peptides on spontaneous motor behavior were analysed. The results show that the latencies of all VER components remain unchanged and the amplitudes of the primary VER were unaffected. Measured at a wide variety of light intensities, however, the amplitudes of the VER afterdischarge were significantly and very similarly diminished by both peptides, the effect of 7-l-phe ACTH4-10 being somewhat stronger than that of 7-d-phe ACTH4-10. These results support the notion, advanced by others, that these peptides have an effect on a CNS vigilance regulating system, yet do not explain the reported opposite effects on active avoidance behavior of the two related peptides. The effects appear specific since spontaneous motor behavior, as index of changes in generalised arousal, is unaffected by these two peptides.", "contents": "The effect of ACTH-analogues on motor behavior and visual evoked responses in rats. Averaged visual evoked responses (VER) in cortical area 17 were recorded one hour after the administration of 7-l-phe ACTH4-10 or 7-d-phe ACTH4-10 to artificially ventilated rats, paralysed with gallamine. In addition, the effects of these peptides on spontaneous motor behavior were analysed. The results show that the latencies of all VER components remain unchanged and the amplitudes of the primary VER were unaffected. Measured at a wide variety of light intensities, however, the amplitudes of the VER afterdischarge were significantly and very similarly diminished by both peptides, the effect of 7-l-phe ACTH4-10 being somewhat stronger than that of 7-d-phe ACTH4-10. These results support the notion, advanced by others, that these peptides have an effect on a CNS vigilance regulating system, yet do not explain the reported opposite effects on active avoidance behavior of the two related peptides. The effects appear specific since spontaneous motor behavior, as index of changes in generalised arousal, is unaffected by these two peptides."} {"id": "PMID:180546", "title": "Effects of REMS deprivation on striatal dopamine and acetylcholine in rats.", "content": "Changes in the concentration of striatal dopamine (DA) and acetylcholine (ACh) in rats deprived of REM sleep for 10 days were compared with those obtained after a 4 day deprivation procedure. Animals placed on small (7 cm dia.) islands surrounded by water were completely deprived of REM sleep but able to obtain some slow-wave sleep. Concentration of striatal DA was significantly increased after 4 days and 10 days of REM sleep deprivation by 73 and 133%, respectively when compared to controls. Levels of ACh in the striatum were significantly enhanced (by 28%) after 10 day, but failed to show significant change after 4 day REM sleep deprivation procedure. The short term locomotor activity was significantly higher in REM sleep-deprived animals. Our data indicate that REM sleep deprivation results in marked alterations of both cholinergic and dopaminergic mechanisms in the rat striatum.", "contents": "Effects of REMS deprivation on striatal dopamine and acetylcholine in rats. Changes in the concentration of striatal dopamine (DA) and acetylcholine (ACh) in rats deprived of REM sleep for 10 days were compared with those obtained after a 4 day deprivation procedure. Animals placed on small (7 cm dia.) islands surrounded by water were completely deprived of REM sleep but able to obtain some slow-wave sleep. Concentration of striatal DA was significantly increased after 4 days and 10 days of REM sleep deprivation by 73 and 133%, respectively when compared to controls. Levels of ACh in the striatum were significantly enhanced (by 28%) after 10 day, but failed to show significant change after 4 day REM sleep deprivation procedure. The short term locomotor activity was significantly higher in REM sleep-deprived animals. Our data indicate that REM sleep deprivation results in marked alterations of both cholinergic and dopaminergic mechanisms in the rat striatum."} {"id": "PMID:180547", "title": "Somatostatin and thyrotropin releasing hormone: central effect on sleep and motor system.", "content": "The hypothalamic hormones, somatostatin (SRIF or GH-RIH) and thyrotropin releasing hormone (TRH) applied intraventricularly into rat brain had a considerable effect on motor function and resulted in profound alterations in the sleep-waking pattern. While TRH induced primarily an increase in exploratory and motor stereotyped behavior, the effect of somatostatin was striking and prolonged: stereotyped circular running in many instances evolved into catatonia, paraplegia-in extension and/or tonic-clonic seizures.", "contents": "Somatostatin and thyrotropin releasing hormone: central effect on sleep and motor system. The hypothalamic hormones, somatostatin (SRIF or GH-RIH) and thyrotropin releasing hormone (TRH) applied intraventricularly into rat brain had a considerable effect on motor function and resulted in profound alterations in the sleep-waking pattern. While TRH induced primarily an increase in exploratory and motor stereotyped behavior, the effect of somatostatin was striking and prolonged: stereotyped circular running in many instances evolved into catatonia, paraplegia-in extension and/or tonic-clonic seizures."} {"id": "PMID:180555", "title": "Office evaluation of breast problems.", "content": "The primary physician's best and most dependable aid to diagnosis of breast problems is a thorough and careful physical examination. A methodical approach is described.", "contents": "Office evaluation of breast problems. The primary physician's best and most dependable aid to diagnosis of breast problems is a thorough and careful physical examination. A methodical approach is described."} {"id": "PMID:180556", "title": "Age and parasuicide ('attempted suicide').", "content": "A one-year cohort of parasuicide patients (n = 882) was divided into three age groups, subdivided by sex where indicated. Systematic comparisons of the groups were made, and significant discrepancies validated using a second cohort of patients. A number of social, demographic and clinical differences were found, as well as some unexpected similarities. The rates for subsequent (completed) suicide were conspicuously different in the six age-sex subgroups.", "contents": "Age and parasuicide ('attempted suicide'). A one-year cohort of parasuicide patients (n = 882) was divided into three age groups, subdivided by sex where indicated. Systematic comparisons of the groups were made, and significant discrepancies validated using a second cohort of patients. A number of social, demographic and clinical differences were found, as well as some unexpected similarities. The rates for subsequent (completed) suicide were conspicuously different in the six age-sex subgroups."} {"id": "PMID:180560", "title": "The vascular tree in the juvenile nasopharyngeal angiofibroma: a report of 10 cases.", "content": "Nasopharyngeal angiofibromas have a characteristic angiographic appearance that will allow operative diagnosis without the dangers of biopsy. Angiography shows the vascularization of the tumour and is of great value to determine the extact extension of the tumour. Subtraction technique is essential. The routine skull-base view is imperative to determine if it is necessary to perform a bilateral angiography.", "contents": "The vascular tree in the juvenile nasopharyngeal angiofibroma: a report of 10 cases. Nasopharyngeal angiofibromas have a characteristic angiographic appearance that will allow operative diagnosis without the dangers of biopsy. Angiography shows the vascularization of the tumour and is of great value to determine the extact extension of the tumour. Subtraction technique is essential. The routine skull-base view is imperative to determine if it is necessary to perform a bilateral angiography."} {"id": "PMID:180561", "title": "Angiography and histopathology of nephroblastomatosis.", "content": "A case of nephroblastomatosis (diffuse bilateral Wilms' tumor) in association with congenital hemihypertrophy is reported and the angiographic findings presented. Serial angiograms and tissue biopsies documented the transition from nodular renal blastema to Wilms' tumor.", "contents": "Angiography and histopathology of nephroblastomatosis. A case of nephroblastomatosis (diffuse bilateral Wilms' tumor) in association with congenital hemihypertrophy is reported and the angiographic findings presented. Serial angiograms and tissue biopsies documented the transition from nodular renal blastema to Wilms' tumor."} {"id": "PMID:180562", "title": "Angiography of nonfunctioning islet cell tumors of the pancreas.", "content": "Two cases of nonfunctioning islet cell tumors were documented angiographically and histologically. The manifestations of islet cell tumors, with emphasis on the nonfunctioning type, are discussed, as are the differences between the functioning and nonfunctioning types.", "contents": "Angiography of nonfunctioning islet cell tumors of the pancreas. Two cases of nonfunctioning islet cell tumors were documented angiographically and histologically. The manifestations of islet cell tumors, with emphasis on the nonfunctioning type, are discussed, as are the differences between the functioning and nonfunctioning types."} {"id": "PMID:180571", "title": "[Binding to chicken liver lactatedehydrogenase (author's transl)].", "content": "Some information about the lactate dehydrogenase NAD binding site has been obtained by working with coenzymes analogs of incomplete molecules. 5'AMP, 5'-ADP, ATP, 5'-c-AMP and 3'(2)-AMP inhibit chicken liver LDH activity competitively with NADH. 5\"-AMP and 5'-ADP show a stronger inhibition power than ATP, suggesting that the presence of one or two phosphate groups at the 5' position of adenosine, is essential for the binding of the coenzyme analogs at the enzyme binding site. Ribose and ribose-5'-P do not appear to inhibit the LDH activity, proving that purine base lacking mononucleotides do not bind to the enzyme. 5\"-ADPG inhibits LDH activity in the exactly as 5'-ADP, showing that ribose moiety may be replaced by glucose, without considerable effects on the coenzyme analog binding. 2'-desoxidenosin-5'-phosphate proves to be a poorer inhibitor of the LDH activity than 5'-AMP, indicating that an interaction between the--OH groups and the amino-acids of the LDH active center takes place. Nicotinamide does not produce any inhibition effect, while NMN and CMP induce a much weaker inhibition than the adenine analogues, thus indicating a lesser binding capacity to the enzyme. Therefore, the LDH binding site seems to show some definite specificity towards the adenina groups of the coenzyme.", "contents": "[Binding to chicken liver lactatedehydrogenase (author's transl)]. Some information about the lactate dehydrogenase NAD binding site has been obtained by working with coenzymes analogs of incomplete molecules. 5'AMP, 5'-ADP, ATP, 5'-c-AMP and 3'(2)-AMP inhibit chicken liver LDH activity competitively with NADH. 5\"-AMP and 5'-ADP show a stronger inhibition power than ATP, suggesting that the presence of one or two phosphate groups at the 5' position of adenosine, is essential for the binding of the coenzyme analogs at the enzyme binding site. Ribose and ribose-5'-P do not appear to inhibit the LDH activity, proving that purine base lacking mononucleotides do not bind to the enzyme. 5\"-ADPG inhibits LDH activity in the exactly as 5'-ADP, showing that ribose moiety may be replaced by glucose, without considerable effects on the coenzyme analog binding. 2'-desoxidenosin-5'-phosphate proves to be a poorer inhibitor of the LDH activity than 5'-AMP, indicating that an interaction between the--OH groups and the amino-acids of the LDH active center takes place. Nicotinamide does not produce any inhibition effect, while NMN and CMP induce a much weaker inhibition than the adenine analogues, thus indicating a lesser binding capacity to the enzyme. Therefore, the LDH binding site seems to show some definite specificity towards the adenina groups of the coenzyme."} {"id": "PMID:180574", "title": "Nuclear protein kinase of brain: effect of S-100 protein.", "content": "The non-histone chromosomal protein fraction isolated from purified brain nuclei possesses protein kinase activity. 93% of this activity is lost by heating at 80 degrees C for 5 min. cAMP does not affect the reaction, but cGMP is inhibitory. In the presence of S-100, an acidic brain-specific protein, phosphate incorporation is enhanced 3 to 4 fold. Bovine serum albumin has no effect whereas histone inhibits activity.", "contents": "Nuclear protein kinase of brain: effect of S-100 protein. The non-histone chromosomal protein fraction isolated from purified brain nuclei possesses protein kinase activity. 93% of this activity is lost by heating at 80 degrees C for 5 min. cAMP does not affect the reaction, but cGMP is inhibitory. In the presence of S-100, an acidic brain-specific protein, phosphate incorporation is enhanced 3 to 4 fold. Bovine serum albumin has no effect whereas histone inhibits activity."} {"id": "PMID:180575", "title": "The growth characteristics of metastases from experimental renal tumors.", "content": "Wistar-Furth rats and BALB/c mice were implanted with tumor cells from metastases or primaries of an experimental Wilms' tumor or an experimental renal cell adenocarcinoma. The survival time, metastasis formation and growth of the primary tumor after implantation of metastatic tumor cells did not exceed those found after implantation of tumor cells from the tumor primaries. It is concluded that the higher growth rate usually found in metastases is not necessarily due to a selection of metastatic cells with a short cell growth cycle but that there are other environmental factors enhancing the growth of metastases.", "contents": "The growth characteristics of metastases from experimental renal tumors. Wistar-Furth rats and BALB/c mice were implanted with tumor cells from metastases or primaries of an experimental Wilms' tumor or an experimental renal cell adenocarcinoma. The survival time, metastasis formation and growth of the primary tumor after implantation of metastatic tumor cells did not exceed those found after implantation of tumor cells from the tumor primaries. It is concluded that the higher growth rate usually found in metastases is not necessarily due to a selection of metastatic cells with a short cell growth cycle but that there are other environmental factors enhancing the growth of metastases."} {"id": "PMID:180576", "title": "Enhanced pulmonary absorption of drugs in rats with experimental silicosis.", "content": "To investigate the effect of pulmonary silicosis on absorption of drugs from the lung, rats were given an intratracheal injection of 50 mg quartz dust, and rates of drug absorption from silicotic and control lungs were compared at 60 and 120 days after treatment. The pulmonary absorption of procaine amide ethobromide and p-aminohippuric acid was increased by 33-41% in animals with silicosis, whereas absorption of procaine amide in silicotic animals was not significantly different from control. The results suggest that silicosis results in an increased porosity of the pulmonary epithelium.", "contents": "Enhanced pulmonary absorption of drugs in rats with experimental silicosis. To investigate the effect of pulmonary silicosis on absorption of drugs from the lung, rats were given an intratracheal injection of 50 mg quartz dust, and rates of drug absorption from silicotic and control lungs were compared at 60 and 120 days after treatment. The pulmonary absorption of procaine amide ethobromide and p-aminohippuric acid was increased by 33-41% in animals with silicosis, whereas absorption of procaine amide in silicotic animals was not significantly different from control. The results suggest that silicosis results in an increased porosity of the pulmonary epithelium."} {"id": "PMID:180577", "title": "Comparisons of antidotal efficacy of chelating drugs upon acute toxicity of Ni(II) in rats.", "content": "Six chelating drugs were administered to rats by im injection at equimolar dosages in order to compare their relative effectiveness in prevention of death after a single parenteral injection of NiCl2. Triethylenetetramine and d-penicillamine were most effective antidotes for acute Ni (II)-toxicity. In order of decreasing antidotal effectiveness, diglycyl-L-histidine-N-methylamide, sodium diethyldithiocarbamate and calcium disodium versenate significantly reduced the acute mortality of rats following ip injection of Ni (II). Alpha-Lipoic acid was not effective as an antidote for acute Ni (II)-toxicity.", "contents": "Comparisons of antidotal efficacy of chelating drugs upon acute toxicity of Ni(II) in rats. Six chelating drugs were administered to rats by im injection at equimolar dosages in order to compare their relative effectiveness in prevention of death after a single parenteral injection of NiCl2. Triethylenetetramine and d-penicillamine were most effective antidotes for acute Ni (II)-toxicity. In order of decreasing antidotal effectiveness, diglycyl-L-histidine-N-methylamide, sodium diethyldithiocarbamate and calcium disodium versenate significantly reduced the acute mortality of rats following ip injection of Ni (II). Alpha-Lipoic acid was not effective as an antidote for acute Ni (II)-toxicity."} {"id": "PMID:180578", "title": "Effect of hydroxycobalamin on the inhibition of cytochrome c oxidase by cyanide. II - In isolated cytochrome C oxidase.", "content": "The effects of hydroxycobalamin on inhibition of the isolated cytochrome c oxidase (EC 1.9.3.1) by cyanide were studied. No effect of hydroxycobalamin (HCo) and cyanocobalamin (CNCo) was observed on isolated cytochrome c oxidase. When cytochrome c oxidase inhibited by cyanide was treated with HCo the reversal of inhibition could be observed through the spectrum of cytochrome c oxidase without reversal of activity; CNCo had no effect. The treatment of cyano-cytochrome c oxidase with HCo suggests that there is the formation of cobalamin-cytochrome c oxidase complex plus CNCo, and it is possible that complex formation would be between the cobalt of cobalamin and proteic part of cytochrome c oxidase.", "contents": "Effect of hydroxycobalamin on the inhibition of cytochrome c oxidase by cyanide. II - In isolated cytochrome C oxidase. The effects of hydroxycobalamin on inhibition of the isolated cytochrome c oxidase (EC 1.9.3.1) by cyanide were studied. No effect of hydroxycobalamin (HCo) and cyanocobalamin (CNCo) was observed on isolated cytochrome c oxidase. When cytochrome c oxidase inhibited by cyanide was treated with HCo the reversal of inhibition could be observed through the spectrum of cytochrome c oxidase without reversal of activity; CNCo had no effect. The treatment of cyano-cytochrome c oxidase with HCo suggests that there is the formation of cobalamin-cytochrome c oxidase complex plus CNCo, and it is possible that complex formation would be between the cobalt of cobalamin and proteic part of cytochrome c oxidase."} {"id": "PMID:180579", "title": "Effect of narcotic dependence and withdrawal on striatal dopamine-sensitive adenylate cyclase and synaptosomal cyclic AMP metabolism.", "content": "In rats rendered tolerant to the dependent on morphine, striatal cyclic AMP metabolism was significantly enhanced as reflected by elevated cyclic AMP levels and adenylate cyclase activity. Following withdrawal from morphine treatment, whereas the activity of straital adenylate cyclase was significantly reduced when compared to morphine-dependent rats, the drop in cyclic AMP was not significant. Although addition of dopamine (40 muM) stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, the activity of dopamine-stimulated enzyme was blocked in animals undergoing withdrawal. The crude synaptosomal fraction of the whole brain obtained from morphine-dependent rats exhibited an even more pronounced increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted for the morphine-naloxone group.", "contents": "Effect of narcotic dependence and withdrawal on striatal dopamine-sensitive adenylate cyclase and synaptosomal cyclic AMP metabolism. In rats rendered tolerant to the dependent on morphine, striatal cyclic AMP metabolism was significantly enhanced as reflected by elevated cyclic AMP levels and adenylate cyclase activity. Following withdrawal from morphine treatment, whereas the activity of straital adenylate cyclase was significantly reduced when compared to morphine-dependent rats, the drop in cyclic AMP was not significant. Although addition of dopamine (40 muM) stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, the activity of dopamine-stimulated enzyme was blocked in animals undergoing withdrawal. The crude synaptosomal fraction of the whole brain obtained from morphine-dependent rats exhibited an even more pronounced increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted for the morphine-naloxone group."} {"id": "PMID:180580", "title": "Ontogenesis of serotonergic systems in rat brain.", "content": "It was shown that the concentration of brain 5-HT rises slowly, reaching mature values by 80 days of age, while the catabolic product of 5-HT, i.e., 5-HIAA, drops from a high perinatal value to lower values by adulthood. This is indicated of poorly developed storage mechanisms at this early period in life. It was also shown that MAO develops at a rapid rate, acquiring mature values by 20 days. The activity of MAO towards substrates develops at different rates, although the general pattern of development is the same.", "contents": "Ontogenesis of serotonergic systems in rat brain. It was shown that the concentration of brain 5-HT rises slowly, reaching mature values by 80 days of age, while the catabolic product of 5-HT, i.e., 5-HIAA, drops from a high perinatal value to lower values by adulthood. This is indicated of poorly developed storage mechanisms at this early period in life. It was also shown that MAO develops at a rapid rate, acquiring mature values by 20 days. The activity of MAO towards substrates develops at different rates, although the general pattern of development is the same."} {"id": "PMID:180581", "title": "Growth kinetic studies of avian infectious bronchitis virus in tracheal organ cultures.", "content": "An egg-adapted vaccine strain (H120) and an organ culture-passaged field strain (HV-10) of avian infectious bronchitis (AIB) virus were propagated in tracheal organ cultures and their growth kinetics examined using nine-day-old embryonated fowl eggs and chick tracheal explants for virus assay. When the H120 strain was assayed in embryonated eggs, titres were approximately log10 2-0 ID50 (50 per cent infectious dose) per ml higher than when assays were performed in tracheal explants. The HV-10 strain, assayed in tracheal explants, yielded higher titres than did the H120 strain, but when assayed in embryonated eggs, yielded only minimal and variable virus titres.", "contents": "Growth kinetic studies of avian infectious bronchitis virus in tracheal organ cultures. An egg-adapted vaccine strain (H120) and an organ culture-passaged field strain (HV-10) of avian infectious bronchitis (AIB) virus were propagated in tracheal organ cultures and their growth kinetics examined using nine-day-old embryonated fowl eggs and chick tracheal explants for virus assay. When the H120 strain was assayed in embryonated eggs, titres were approximately log10 2-0 ID50 (50 per cent infectious dose) per ml higher than when assays were performed in tracheal explants. The HV-10 strain, assayed in tracheal explants, yielded higher titres than did the H120 strain, but when assayed in embryonated eggs, yielded only minimal and variable virus titres."} {"id": "PMID:180582", "title": "The pathogenesis of pulmonary emphysema (II).", "content": "The most important primary cause of generalized pulmonary emphysema is in all probability the loss of mechanical stability of the connective tissue framework in the lung parenchyma. The complexity of the interrelations and interdependencies between the fibres and the ground substance, leads to the mapping out of a more detailed outline of the vulnerable parts in a similar framework. It is concluded that the junctions especially constitute weak spots. Glycosaminoglycans, glycoproteins and proteoglycans particularly hold a key position as cementing substances. The importance of female sex hormones in the metabolism of the ground substance is indicated. A survey is given of the possible threats to a similar system. An attempt is made to disentangle the multitude of possible pathogenetic pathways which lead to emphysematous disintegration. Perspectives of future emphysema research are discussed on the basis of these considerations. Preventive, protective, and reconstructive measures are proposed.", "contents": "The pathogenesis of pulmonary emphysema (II). The most important primary cause of generalized pulmonary emphysema is in all probability the loss of mechanical stability of the connective tissue framework in the lung parenchyma. The complexity of the interrelations and interdependencies between the fibres and the ground substance, leads to the mapping out of a more detailed outline of the vulnerable parts in a similar framework. It is concluded that the junctions especially constitute weak spots. Glycosaminoglycans, glycoproteins and proteoglycans particularly hold a key position as cementing substances. The importance of female sex hormones in the metabolism of the ground substance is indicated. A survey is given of the possible threats to a similar system. An attempt is made to disentangle the multitude of possible pathogenetic pathways which lead to emphysematous disintegration. Perspectives of future emphysema research are discussed on the basis of these considerations. Preventive, protective, and reconstructive measures are proposed."} {"id": "PMID:180585", "title": "Quantitative bone scanning.", "content": "The use of a computer coupled on-line with the scintillation camera allows an improvement of the finding of skeletal scintigraphy realized with 99mTc-pyrophosphate, making possible the identification of the smallest bone lesions. It also makes possible the quantification of the uptake degree of the radioindicator demonstrating, in normal subjects, an uptake ratio between the various skeletal segments of 1.07 +/- 0.06. In 44 metastatic lesions the ratio was 1.80 +/- 0.32, whilst in 14 areas of slight hyperfixation of the tracer a value of 1.24 +/- 0.09 was found. Since we were dealing with patients suffering from metastatic bone neoplasms, the authors outline the possibility that the quantification of data will allow the demonstration of the bone metastases even more precociously than with traditional scintigraphix examination.", "contents": "Quantitative bone scanning. The use of a computer coupled on-line with the scintillation camera allows an improvement of the finding of skeletal scintigraphy realized with 99mTc-pyrophosphate, making possible the identification of the smallest bone lesions. It also makes possible the quantification of the uptake degree of the radioindicator demonstrating, in normal subjects, an uptake ratio between the various skeletal segments of 1.07 +/- 0.06. In 44 metastatic lesions the ratio was 1.80 +/- 0.32, whilst in 14 areas of slight hyperfixation of the tracer a value of 1.24 +/- 0.09 was found. Since we were dealing with patients suffering from metastatic bone neoplasms, the authors outline the possibility that the quantification of data will allow the demonstration of the bone metastases even more precociously than with traditional scintigraphix examination."} {"id": "PMID:180584", "title": "Pathology produced by isocyanates: methods of immunological investigation.", "content": "A group of 182 workers exposed to diisocyanates (varnishers, carpenters, producers of polyurethane resins and expanded plastic) were examined to study the immunogenic capacity of these substances. The skin tests, particularly the intradermal tests, revealed reactions of the immediate, accelerated and/or delayed types due to the presence of IgE and IgG, in addition to responses of the cellular type. This was confirmed by passive transfer in guinea-pigs and man and immunohaematological tests such as passive haemagglutination and lymphocyte transformation. In 4 cases it was possible to demonstrate thermoresistant, homocytotropic immunoglobulins, that were not dependent on complement and behaved like reagins (i.e. short-term anaphylactic IgG). Exposure tests were performed on 45 cases; the results are analyzed and compared with those of the skin tests. It is concluded that both these groups of tests are of value in investigating the aetiopathogenesis of the pathology of the isocyanates: the skin tests for initial screening, and then the exposure tests for resolving doubtful diagnoses. Cross-reactions were also demonstrated between toluene-diisocyanate and methylene-diisocyanate. Two phases could be considered in the pathogenesis; in the first phase, signs of inflammation appeared at the primary sites of contact with the irritant, then the ability of the diisocyanates to form a conjugate with organic proteins results in the production of a complete antigen and consequent sensitization of the exposed person. The appearance of symptoms naturally depends on subsequent exposure and the immunogenic capacity of the patient: the response is mainly of the reagin type in atopic patients and of type 3 in non-atopic patients.", "contents": "Pathology produced by isocyanates: methods of immunological investigation. A group of 182 workers exposed to diisocyanates (varnishers, carpenters, producers of polyurethane resins and expanded plastic) were examined to study the immunogenic capacity of these substances. The skin tests, particularly the intradermal tests, revealed reactions of the immediate, accelerated and/or delayed types due to the presence of IgE and IgG, in addition to responses of the cellular type. This was confirmed by passive transfer in guinea-pigs and man and immunohaematological tests such as passive haemagglutination and lymphocyte transformation. In 4 cases it was possible to demonstrate thermoresistant, homocytotropic immunoglobulins, that were not dependent on complement and behaved like reagins (i.e. short-term anaphylactic IgG). Exposure tests were performed on 45 cases; the results are analyzed and compared with those of the skin tests. It is concluded that both these groups of tests are of value in investigating the aetiopathogenesis of the pathology of the isocyanates: the skin tests for initial screening, and then the exposure tests for resolving doubtful diagnoses. Cross-reactions were also demonstrated between toluene-diisocyanate and methylene-diisocyanate. Two phases could be considered in the pathogenesis; in the first phase, signs of inflammation appeared at the primary sites of contact with the irritant, then the ability of the diisocyanates to form a conjugate with organic proteins results in the production of a complete antigen and consequent sensitization of the exposed person. The appearance of symptoms naturally depends on subsequent exposure and the immunogenic capacity of the patient: the response is mainly of the reagin type in atopic patients and of type 3 in non-atopic patients."} {"id": "PMID:180589", "title": "Progressive supranuclear palsy: report of two cases (author's transl).", "content": "Two cases of progressive supranuclear palsy (PSP) are reported in two men (49 and 75years old) who for one and four years respectively had sudden falling while walking. Rigidity of the neck was an carly feature that prgressed to involve the upper trunk while \"subcortical dementia\", dysarthria and dysphagia appeared. They had a complete paralysis of vertical eye movements and slow horizontal voluntary eye movements. Oculocephalic reflexes were intact. On caloric stimulation vestibulo-ocular responses were present but only slow saccadic eye movements were observed. With surface electrodes eye movements were studied during the REM phase of sleep. Our patients had both vertical and horizontal eye movements during paradoxal sleep. This findings is in keeping with a supranuclear ophtalmoplegia, and may help in antemorten diagnosis of PSP.", "contents": "Progressive supranuclear palsy: report of two cases (author's transl). Two cases of progressive supranuclear palsy (PSP) are reported in two men (49 and 75years old) who for one and four years respectively had sudden falling while walking. Rigidity of the neck was an carly feature that prgressed to involve the upper trunk while \"subcortical dementia\", dysarthria and dysphagia appeared. They had a complete paralysis of vertical eye movements and slow horizontal voluntary eye movements. Oculocephalic reflexes were intact. On caloric stimulation vestibulo-ocular responses were present but only slow saccadic eye movements were observed. With surface electrodes eye movements were studied during the REM phase of sleep. Our patients had both vertical and horizontal eye movements during paradoxal sleep. This findings is in keeping with a supranuclear ophtalmoplegia, and may help in antemorten diagnosis of PSP."} {"id": "PMID:180590", "title": "[Hormonal investigations in a patient with mucopolisaccharidosis (author's transl)].", "content": "In one patient with mucopolisaccharidosis endocrine investigation were performed. The results indicate an impaired regulation of hypothalamus-hypophysis-adrenocortical system. The hypothalamus GH sstem appears to be involved to a lesser extent. A dysfunction of the central nervous system is suggested.", "contents": "[Hormonal investigations in a patient with mucopolisaccharidosis (author's transl)]. In one patient with mucopolisaccharidosis endocrine investigation were performed. The results indicate an impaired regulation of hypothalamus-hypophysis-adrenocortical system. The hypothalamus GH sstem appears to be involved to a lesser extent. A dysfunction of the central nervous system is suggested."} {"id": "PMID:180596", "title": "Ethanol-induced depletion of cerebellar guanosine 3',5' -cyclic monophosphate.", "content": "Single doses of ethanol a severe depletion (95 percent) of cerebellar guanosine 3',5' -cyclic monophosphate (cyclic GMP) within 1 hour after administration. The degree of this depletion is dose-dependent and is a function of the amount of ethanol in the blood. Interactions between ethanol and cyclic GMP may account for some of the intoxicating properties of ethanol.", "contents": "Ethanol-induced depletion of cerebellar guanosine 3',5' -cyclic monophosphate. Single doses of ethanol a severe depletion (95 percent) of cerebellar guanosine 3',5' -cyclic monophosphate (cyclic GMP) within 1 hour after administration. The degree of this depletion is dose-dependent and is a function of the amount of ethanol in the blood. Interactions between ethanol and cyclic GMP may account for some of the intoxicating properties of ethanol."} {"id": "PMID:180597", "title": "Enhanced template activity in chromatin from adrenal medulla after phosphorylation of chromosomal proteins.", "content": "Translocation of protein kinase to the nucleus had been implicated earlier in the transsynaptic control of gene expression mediated by cholinergic nerves in adrenal medulla. Phosphorylation of chromosomal proteins by adenosine 3',5'-monophosphate-dependent protein kinase and adenosine 3',5'-monophosphate enhances the template activity of chromatin from adrenal medulla. When homologous RNA polymerase II is used the relative activation is greater than that obtained with Escherichia coli RNA polymerase. The substrate for such phosphorylation does not seem to be RNA polymerase II. Phosphorylation of specific acidic protein probably mediates this enhancement of template activity.", "contents": "Enhanced template activity in chromatin from adrenal medulla after phosphorylation of chromosomal proteins. Translocation of protein kinase to the nucleus had been implicated earlier in the transsynaptic control of gene expression mediated by cholinergic nerves in adrenal medulla. Phosphorylation of chromosomal proteins by adenosine 3',5'-monophosphate-dependent protein kinase and adenosine 3',5'-monophosphate enhances the template activity of chromatin from adrenal medulla. When homologous RNA polymerase II is used the relative activation is greater than that obtained with Escherichia coli RNA polymerase. The substrate for such phosphorylation does not seem to be RNA polymerase II. Phosphorylation of specific acidic protein probably mediates this enhancement of template activity."} {"id": "PMID:180598", "title": "Electrotonic processing of information by brain cells.", "content": "In contrast to well-studied through-protection neurons that propagate information from one region to another in the central nervous system, short-axon or axonless neurons form local circuits, transmitting signals through synapses and electrical junctions between their dendrites. Interaction in this dendritic network proceeds without spike action potentials. Interaction is mediated by graded electrotonic changes of potential and is transmitted through high sensitivity (submillivolt threshold) synapses rather than by lower sensitivity (20 to 100-mv threshold) synapses typical of projection neurons. A crucial feature of local circuits is their high degree of interaction both through specialized junctional structures and through the extracellular fields generated by local and more distant brain regions. The anatomical evidence for the nature and distribution of neuronal local circuits in the nervous system is surveyed. Bioelectric mechanisms are discussed in relation to the special properties of local circuits, including dendrodendritic synapses, synaptic sensitivity, electrotonic coupling, and field effects. Intraneuronal and interneuronal transport of various types of substances suggests that the biochemical and the bioelectrical parameters are functionally interwoven. Through such interactions neuronal local circuits, with their distinctive properties, may play an essential role in higher brain function.", "contents": "Electrotonic processing of information by brain cells. In contrast to well-studied through-protection neurons that propagate information from one region to another in the central nervous system, short-axon or axonless neurons form local circuits, transmitting signals through synapses and electrical junctions between their dendrites. Interaction in this dendritic network proceeds without spike action potentials. Interaction is mediated by graded electrotonic changes of potential and is transmitted through high sensitivity (submillivolt threshold) synapses rather than by lower sensitivity (20 to 100-mv threshold) synapses typical of projection neurons. A crucial feature of local circuits is their high degree of interaction both through specialized junctional structures and through the extracellular fields generated by local and more distant brain regions. The anatomical evidence for the nature and distribution of neuronal local circuits in the nervous system is surveyed. Bioelectric mechanisms are discussed in relation to the special properties of local circuits, including dendrodendritic synapses, synaptic sensitivity, electrotonic coupling, and field effects. Intraneuronal and interneuronal transport of various types of substances suggests that the biochemical and the bioelectrical parameters are functionally interwoven. Through such interactions neuronal local circuits, with their distinctive properties, may play an essential role in higher brain function."} {"id": "PMID:180599", "title": "Brainstem neurons without spontaneous unit discharge.", "content": "A new class of single neurons showing no spontaneous activity in waking, rapid eye movement sleep, and slow-wave sleep was found in the brainstem of unrestrained cats. Systematic testing showed that these cells discharge only in response to specific stimuli and remain silent for as long as 40 minutes in the absence of stimulation. Silent cells were widely distributed in the pons and midbrain and constituted a major percentage of observed neurons. The economy of discharge shown by these cells contrasts with the spontaneous activity of virtually all other neurons that have been observed in the brains of unrestrained animals and suggests the widespread existence of specialized neural systems that show only phasic activity.", "contents": "Brainstem neurons without spontaneous unit discharge. A new class of single neurons showing no spontaneous activity in waking, rapid eye movement sleep, and slow-wave sleep was found in the brainstem of unrestrained cats. Systematic testing showed that these cells discharge only in response to specific stimuli and remain silent for as long as 40 minutes in the absence of stimulation. Silent cells were widely distributed in the pons and midbrain and constituted a major percentage of observed neurons. The economy of discharge shown by these cells contrasts with the spontaneous activity of virtually all other neurons that have been observed in the brains of unrestrained animals and suggests the widespread existence of specialized neural systems that show only phasic activity."} {"id": "PMID:180600", "title": "Lymphocyte-differentiating hormone of bursa of fabricius.", "content": "Induction of early lymphocyte differentiation was studied in vitro in fractionated bone marrow cells of newly hatched chickens, with alloantiserums to identify newly differentiated B cells (Bu-1+) and T cells (Th-1+). Thymus extract induced selective T cell differentiation; the activity of the extract corresponds to that of thymopoietin. Bursal extract induced both B cell and T cell differentiation, but at lower concentrations B cell differentiation was always greater. This activity is ascribed to a lymphocyte-differentiating hormone of the bursa of Fabricius, for which the name bursopoietin is suggested.", "contents": "Lymphocyte-differentiating hormone of bursa of fabricius. Induction of early lymphocyte differentiation was studied in vitro in fractionated bone marrow cells of newly hatched chickens, with alloantiserums to identify newly differentiated B cells (Bu-1+) and T cells (Th-1+). Thymus extract induced selective T cell differentiation; the activity of the extract corresponds to that of thymopoietin. Bursal extract induced both B cell and T cell differentiation, but at lower concentrations B cell differentiation was always greater. This activity is ascribed to a lymphocyte-differentiating hormone of the bursa of Fabricius, for which the name bursopoietin is suggested."} {"id": "PMID:180601", "title": "Specificity of in vitro binding of primate Type C viral RNA and the homologous viral p12 core protein.", "content": "The binding of type C viral p12 proteins to purified viral RNA has been examined in vitro with the use of a family of closely related infectious primate type C viruses--the woolly monkey (SSAV) and gibbon (GALV) group. This in vitro protein-RNA binding is type specific. The system should serve as a model for studies of the evolution of nucleic acid binding proteins.", "contents": "Specificity of in vitro binding of primate Type C viral RNA and the homologous viral p12 core protein. The binding of type C viral p12 proteins to purified viral RNA has been examined in vitro with the use of a family of closely related infectious primate type C viruses--the woolly monkey (SSAV) and gibbon (GALV) group. This in vitro protein-RNA binding is type specific. The system should serve as a model for studies of the evolution of nucleic acid binding proteins."} {"id": "PMID:180602", "title": "Embryonal neoplasms in the opossum: a new model for solid tumors of infancy and childhood.", "content": "Opossums fed the chemical carcinogen ethyl nitrosourea early in postnatal life developed a variety of epithelial and mesenchymal embryonal neoplasms that were closely analogous, in morphology and biological behavior, to tumors of human infancy and childhood for which experimental models in laboratory animals are either imprecise or nonexistent. The embryonal tumors were found in association with, and occasionally at the same sites as, a limited number of malformations.", "contents": "Embryonal neoplasms in the opossum: a new model for solid tumors of infancy and childhood. Opossums fed the chemical carcinogen ethyl nitrosourea early in postnatal life developed a variety of epithelial and mesenchymal embryonal neoplasms that were closely analogous, in morphology and biological behavior, to tumors of human infancy and childhood for which experimental models in laboratory animals are either imprecise or nonexistent. The embryonal tumors were found in association with, and occasionally at the same sites as, a limited number of malformations."} {"id": "PMID:180603", "title": "Phosphoribosylpyrophosphate synthetase is elevated in fibroblasts from patients with the Lesch-Nyhan syndrome.", "content": "In subconfluent cultures of fibroblasts from patients with complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase activity is elevated. The abnormally high catalytic activity of the synthetase appears to account for the overproduction of purines by the cultured mutant cells and presumably for that by the patients.", "contents": "Phosphoribosylpyrophosphate synthetase is elevated in fibroblasts from patients with the Lesch-Nyhan syndrome. In subconfluent cultures of fibroblasts from patients with complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase activity is elevated. The abnormally high catalytic activity of the synthetase appears to account for the overproduction of purines by the cultured mutant cells and presumably for that by the patients."} {"id": "PMID:180604", "title": "Insulin binding to cultured human fibroblasts increases with normal and precocious aging.", "content": "Specific and nonspecific [125I]insulin binding and concentration of unlabeled hormone producing 50 percent competition with 1.0 nanomolar [125I]insulin for specific binding sites correlated positively with age of fibroblast donors. Cells from four children with precocious aging--three with progeria and one with Rothmund syndrome-resembled those from the chronologically old.", "contents": "Insulin binding to cultured human fibroblasts increases with normal and precocious aging. Specific and nonspecific [125I]insulin binding and concentration of unlabeled hormone producing 50 percent competition with 1.0 nanomolar [125I]insulin for specific binding sites correlated positively with age of fibroblast donors. Cells from four children with precocious aging--three with progeria and one with Rothmund syndrome-resembled those from the chronologically old."} {"id": "PMID:180605", "title": "Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus.", "content": "Multiple small injections of streptozotocin in mice produce pancreatic insulitis, with progression to nearly complete beta cell destruction and diabetes mellitus. The timing and appearance of the inflammatory islet lesions suggest but do not prove that streptozotocin acts by initiating a cell-mediated immune reaction. Ultrastructural evidence of abundant type C viruses within beta cells of treated mice suggests that streptozotocin may activate murine leukemia virus in vivo in susceptible hosts.", "contents": "Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Multiple small injections of streptozotocin in mice produce pancreatic insulitis, with progression to nearly complete beta cell destruction and diabetes mellitus. The timing and appearance of the inflammatory islet lesions suggest but do not prove that streptozotocin acts by initiating a cell-mediated immune reaction. Ultrastructural evidence of abundant type C viruses within beta cells of treated mice suggests that streptozotocin may activate murine leukemia virus in vivo in susceptible hosts."} {"id": "PMID:180606", "title": "[Osteochondritis dissecans and osteonecrosis of the lower end of the femur. Value of bone marrow functional exploration].", "content": "The authors report the results of 19 functional investigations carried out for osteochondritis in 11 cases, and osteonecrosis of the knee in 8 cases. The 8 cases of osteonecrosis all had hemodynamic disorders with increased pressure in the bone marrow and stasis due to circulatory obstruction. On the other hand, 5 cases of osteochondritis out of the 11 explored had no disturbance of marrow blood supply. However, of the 6 cases of osteochondritis with vascular disorders, there were 5 who had some other reason which might explain the disorder blood supply within the bone. It thus seems that one may contrast two types of disease: -One, characterized by an intra-osseous circulatory disorder for which one might reserve the terms osteonecrosis, which occurs in patients aged over 60 years, but which may be observed in juvenile forms. - The other, characterised by the absence of any hemodynamic disturbance and in which the foreign body seems to result from a very localised disorder which does not affect the bone marrow blood supply. One may use here the term, osteochondritis. We propose to substitute this physiopathological classification for the classical division based on age and on X-rays. Investigation of the blood supply of the bone, permits, as with strontium, early diagnosis at a pre-radiological stage.", "contents": "[Osteochondritis dissecans and osteonecrosis of the lower end of the femur. Value of bone marrow functional exploration]. The authors report the results of 19 functional investigations carried out for osteochondritis in 11 cases, and osteonecrosis of the knee in 8 cases. The 8 cases of osteonecrosis all had hemodynamic disorders with increased pressure in the bone marrow and stasis due to circulatory obstruction. On the other hand, 5 cases of osteochondritis out of the 11 explored had no disturbance of marrow blood supply. However, of the 6 cases of osteochondritis with vascular disorders, there were 5 who had some other reason which might explain the disorder blood supply within the bone. It thus seems that one may contrast two types of disease: -One, characterized by an intra-osseous circulatory disorder for which one might reserve the terms osteonecrosis, which occurs in patients aged over 60 years, but which may be observed in juvenile forms. - The other, characterised by the absence of any hemodynamic disturbance and in which the foreign body seems to result from a very localised disorder which does not affect the bone marrow blood supply. One may use here the term, osteochondritis. We propose to substitute this physiopathological classification for the classical division based on age and on X-rays. Investigation of the blood supply of the bone, permits, as with strontium, early diagnosis at a pre-radiological stage."} {"id": "PMID:180607", "title": "[Tumors of the glomus jugulare].", "content": "Tumours of the glomus jugulare always raise diagnostic and therapeutic problems. We decided to review the pathology and clinical findings whilst reporting a typical case found on our neurology unit. After a brief review of the embryology, anatomy and histology of the glomus jugulare, the authors report the case of a patient who presented a recurrent intracranial form with involvement of several cranial nerves, together with associated involvement of the carotid glomus. This was a familial disease. The patient was operated on with excellent results. The authors then present a clinical description of the various signs in glomus tumours,; depending more on the origin of the tumours than on the length of history. They then criticize the diagnostic interest of radiology, emphasizing the interest of angiography which may demonstrate a pathological vascular focus derived from the internal carotid artery together with the vertebro-basilar system. Retrograde jugulography also provides important information. The treatment of glomus jugulare tumours is, above all, surgical. They are approached through the ear in order to localise the intra-petrous part, or else, they may be approached through the skull. A combined otological and neuro-surgical approach to sometimes necessary for the lesion may involve both the petromastoid region and the posterior cerebral fossa. Radiotherapy is often advised after operation, in view of the importance of the vascular component of these tumours. The results of treatment are, on the whole, satisfactory.", "contents": "[Tumors of the glomus jugulare]. Tumours of the glomus jugulare always raise diagnostic and therapeutic problems. We decided to review the pathology and clinical findings whilst reporting a typical case found on our neurology unit. After a brief review of the embryology, anatomy and histology of the glomus jugulare, the authors report the case of a patient who presented a recurrent intracranial form with involvement of several cranial nerves, together with associated involvement of the carotid glomus. This was a familial disease. The patient was operated on with excellent results. The authors then present a clinical description of the various signs in glomus tumours,; depending more on the origin of the tumours than on the length of history. They then criticize the diagnostic interest of radiology, emphasizing the interest of angiography which may demonstrate a pathological vascular focus derived from the internal carotid artery together with the vertebro-basilar system. Retrograde jugulography also provides important information. The treatment of glomus jugulare tumours is, above all, surgical. They are approached through the ear in order to localise the intra-petrous part, or else, they may be approached through the skull. A combined otological and neuro-surgical approach to sometimes necessary for the lesion may involve both the petromastoid region and the posterior cerebral fossa. Radiotherapy is often advised after operation, in view of the importance of the vascular component of these tumours. The results of treatment are, on the whole, satisfactory."} {"id": "PMID:180608", "title": "[Infections during malignant blood diseases. Value of the carbenicillin-gentamicin combination].", "content": "The association of carbenicillin and gentamicin was used as a routine in the early treatment of 48 attacks of fever, in 38 patients who mostly had acute leukemia and marrow aplasia. The attacks of infection may be classified as follows: 30% septicemia, 30% local infections, 40% no bacteria were identified. Among the septicemias, we noted 5 septicemias due to pyocyaneus, 4 due to klebsiella. On the whole, in the attacks of fever, the association of carbenicillin and gentamicin proved effective in 70% of cases, but a cure was obtained in only 56% of cases. In vitro, the association carbenicillin-gentamicin proved justified in 70% of cases. There was no special intolerance, apart from a few cases of hypokalemic alkalosis. The association carbenicillin-gentamicin, by its broad spectrum and especially in view of its elective effect on the pyocyaneus is an excellent initial form of antibiotic therapy, when faced with infection in a patient with malignant blood disease. However, it should be recognised that the efficacy of this association depends on the number of circulating polynuclear cells and that some bacteria, such as the klebsiella, are clear cells and that some bacteria, such as the klebsiella, are often resistant to this antibiotic association.", "contents": "[Infections during malignant blood diseases. Value of the carbenicillin-gentamicin combination]. The association of carbenicillin and gentamicin was used as a routine in the early treatment of 48 attacks of fever, in 38 patients who mostly had acute leukemia and marrow aplasia. The attacks of infection may be classified as follows: 30% septicemia, 30% local infections, 40% no bacteria were identified. Among the septicemias, we noted 5 septicemias due to pyocyaneus, 4 due to klebsiella. On the whole, in the attacks of fever, the association of carbenicillin and gentamicin proved effective in 70% of cases, but a cure was obtained in only 56% of cases. In vitro, the association carbenicillin-gentamicin proved justified in 70% of cases. There was no special intolerance, apart from a few cases of hypokalemic alkalosis. The association carbenicillin-gentamicin, by its broad spectrum and especially in view of its elective effect on the pyocyaneus is an excellent initial form of antibiotic therapy, when faced with infection in a patient with malignant blood disease. However, it should be recognised that the efficacy of this association depends on the number of circulating polynuclear cells and that some bacteria, such as the klebsiella, are clear cells and that some bacteria, such as the klebsiella, are often resistant to this antibiotic association."} {"id": "PMID:180609", "title": "[Results of medical treatment of gastroduodenal ulcers with disordered gastric emptying].", "content": "The efficacy of medical treatment was studied in 53 patients with a peptic ulcer responsible for disturbed gastric emptying. An improvement in gastric emptying was noted in 38 cases and persistence of the disorder in 15 cases. These results were not related to the dose of anticholinergic drug, nor to the degree of disturbance in gastric emptying. Only one improvement was noted out of 7 cases of pyloric ulcer. A relapse of disturbed gastric emptying, occurred in 17 out of 38 patients who were initially improved. 25 patients out of 53 were finally operated on, 15 owing to persistence of the gastric emptying disturbance under treatment and 10 owing to a relapse. Out of 18 gastrectomy specimens, the ulcer was found to be healed in 7 cases. It seems that disturbed gastric emptying may be due to fixed deformities of the pylorus which are little changed by medical treatment, and minor disturbances of emptying regress well under treatment. Disturbed gastric emptying due tp pyloric ulcer is the most difficult to treat medically.", "contents": "[Results of medical treatment of gastroduodenal ulcers with disordered gastric emptying]. The efficacy of medical treatment was studied in 53 patients with a peptic ulcer responsible for disturbed gastric emptying. An improvement in gastric emptying was noted in 38 cases and persistence of the disorder in 15 cases. These results were not related to the dose of anticholinergic drug, nor to the degree of disturbance in gastric emptying. Only one improvement was noted out of 7 cases of pyloric ulcer. A relapse of disturbed gastric emptying, occurred in 17 out of 38 patients who were initially improved. 25 patients out of 53 were finally operated on, 15 owing to persistence of the gastric emptying disturbance under treatment and 10 owing to a relapse. Out of 18 gastrectomy specimens, the ulcer was found to be healed in 7 cases. It seems that disturbed gastric emptying may be due to fixed deformities of the pylorus which are little changed by medical treatment, and minor disturbances of emptying regress well under treatment. Disturbed gastric emptying due tp pyloric ulcer is the most difficult to treat medically."} {"id": "PMID:180610", "title": "[Septicemic complications of venous perfusion catheterization. 4 years' experience in an intensive care unit].", "content": "Septicemia is a complication of prolonged venous catheterisation; although rare, is at present important owing to the severity of the condition and the possibility of prevention. The severity should lead one to very careful precautions to avoid sepsis, which antibiotic therapy and emergencies often lead one to neglect. The development of research on the prophylaxis of septicemia suggests that in the future, prolonged intravenous fluid may be given less dangerously. They are usually essential during the initial stages of intensive care.", "contents": "[Septicemic complications of venous perfusion catheterization. 4 years' experience in an intensive care unit]. Septicemia is a complication of prolonged venous catheterisation; although rare, is at present important owing to the severity of the condition and the possibility of prevention. The severity should lead one to very careful precautions to avoid sepsis, which antibiotic therapy and emergencies often lead one to neglect. The development of research on the prophylaxis of septicemia suggests that in the future, prolonged intravenous fluid may be given less dangerously. They are usually essential during the initial stages of intensive care."} {"id": "PMID:180611", "title": "[Cardiac insufficiency caused by the use of daunorubicin. Clinical and developmental study of 4 recent cases].", "content": "Out of a total of 126 patients with acute lymphoblastic leukemia, including 69 children aged less than 15 years, and 57 adults aged less than 60 years, who were treated with daunomycin (D.N.R.) initially and with several courses of reinduction, we noted 4 cases of decompensated heart failure (3.1%). 3 cases occurred in children aged 4, 5 and 5 years, and in the last case, in a young adult, of 19 years. Three of these patients were in complete remission of the blood and were only undergoing courses of reinduction. The 4th was in incomplete remission. When symptoms first occurred, about 2 months after the last injection of D.N.R. the total dose administered varied between 14 and 31 mg/kg, extending over periods of 5 to 16 months (average monthly dose 1.9 to 2.8 mg/kg). Except in one case, the course only mildly influenced by the symptomatic treatment and death occurred in 3 patients within from 15 days to 5 months after the onset of the first symptoms. The last patient is still alive and seems stabilised with a follow up period of 9 months. The responsibility of D.N.R. in the development of this myocarditis appears very likely. The unforeseable character of such complications, which are independent of age, and not necessarily linked to any excessive dosage, should be taken into consideration in the indications for D.N.R. in spite of their relative rarity.", "contents": "[Cardiac insufficiency caused by the use of daunorubicin. Clinical and developmental study of 4 recent cases]. Out of a total of 126 patients with acute lymphoblastic leukemia, including 69 children aged less than 15 years, and 57 adults aged less than 60 years, who were treated with daunomycin (D.N.R.) initially and with several courses of reinduction, we noted 4 cases of decompensated heart failure (3.1%). 3 cases occurred in children aged 4, 5 and 5 years, and in the last case, in a young adult, of 19 years. Three of these patients were in complete remission of the blood and were only undergoing courses of reinduction. The 4th was in incomplete remission. When symptoms first occurred, about 2 months after the last injection of D.N.R. the total dose administered varied between 14 and 31 mg/kg, extending over periods of 5 to 16 months (average monthly dose 1.9 to 2.8 mg/kg). Except in one case, the course only mildly influenced by the symptomatic treatment and death occurred in 3 patients within from 15 days to 5 months after the onset of the first symptoms. The last patient is still alive and seems stabilised with a follow up period of 9 months. The responsibility of D.N.R. in the development of this myocarditis appears very likely. The unforeseable character of such complications, which are independent of age, and not necessarily linked to any excessive dosage, should be taken into consideration in the indications for D.N.R. in spite of their relative rarity."} {"id": "PMID:180614", "title": "Wilms' tumor with bony metastases.", "content": "A case of Wilms' tumor with extensive bony metastases and involvement of unusual sites such as lacrimal and salivary glands without pulmonary metastases is presented.", "contents": "Wilms' tumor with bony metastases. A case of Wilms' tumor with extensive bony metastases and involvement of unusual sites such as lacrimal and salivary glands without pulmonary metastases is presented."} {"id": "PMID:180615", "title": "Carcinoma of the colon in a child.", "content": "A case of mucinous adenocarcinoma of the colon in a 12-year-old girl is reported. There was no evidence of pre-existing familial polyposis or ulcerative colitis, conditions which predispose to colon carcinoma in childhood. A review of the literature revealed 103 previously reported cases. The salient features of the disease are discussed.", "contents": "Carcinoma of the colon in a child. A case of mucinous adenocarcinoma of the colon in a 12-year-old girl is reported. There was no evidence of pre-existing familial polyposis or ulcerative colitis, conditions which predispose to colon carcinoma in childhood. A review of the literature revealed 103 previously reported cases. The salient features of the disease are discussed."} {"id": "PMID:180619", "title": "Primary carcinoma of the liver.", "content": "Four hundred and six patients with primary carcinoma of the liver were admitted to the University Surgical Service at this hospital. The males predominated, 5:1, and except for two patients, all were Chinese. The Hong Kong-born Chinese appeared to be relatively free of the disease which was common among the immigrants from the province of China adjoining Hong Kong. In 199 patients no treatment was possible, while in 83, resection was carried out. In 61 patients, surgical treatment was obligatory because of spontaneous rupture. In the remaining 81 patients, a clinical trial of five categories--hepatic dearterialization, hepatic arterial infusion of 5-fluorouracil, hepatic arterial ligation and portal venous infusion of 5-fluorouracil, radiotherapy and no treatment--was carried out.", "contents": "Primary carcinoma of the liver. Four hundred and six patients with primary carcinoma of the liver were admitted to the University Surgical Service at this hospital. The males predominated, 5:1, and except for two patients, all were Chinese. The Hong Kong-born Chinese appeared to be relatively free of the disease which was common among the immigrants from the province of China adjoining Hong Kong. In 199 patients no treatment was possible, while in 83, resection was carried out. In 61 patients, surgical treatment was obligatory because of spontaneous rupture. In the remaining 81 patients, a clinical trial of five categories--hepatic dearterialization, hepatic arterial infusion of 5-fluorouracil, hepatic arterial ligation and portal venous infusion of 5-fluorouracil, radiotherapy and no treatment--was carried out."} {"id": "PMID:180620", "title": "Monitoring of visual function during parasellar surgery.", "content": "Damage to the visual system is an unfortunate complication of surgery in the area of the optic chiasm. It is now possible tomonitor the functional status of the visual system intreoperatively at regulat intervals. This is accomplished by recording the Visual Evoked Response to flashes of light from light-emitting-eiodes. These diodes are embedded in a special plastic shell which inserts under the eye lids of each eye. Since the light comes from the diodes in the plastic shell, there is no need to disturb the surgical procedure when a test run is desired. A record is obtained by averaging 100 three-per-second flashes.", "contents": "Monitoring of visual function during parasellar surgery. Damage to the visual system is an unfortunate complication of surgery in the area of the optic chiasm. It is now possible tomonitor the functional status of the visual system intreoperatively at regulat intervals. This is accomplished by recording the Visual Evoked Response to flashes of light from light-emitting-eiodes. These diodes are embedded in a special plastic shell which inserts under the eye lids of each eye. Since the light comes from the diodes in the plastic shell, there is no need to disturb the surgical procedure when a test run is desired. A record is obtained by averaging 100 three-per-second flashes."} {"id": "PMID:180621", "title": "Cerebellar glioblastoma multiforme in an adult.", "content": "One of the few well documented cases of cerebellar glioblastoma multiforme in an adult is reported. In addition, to our knowledge, it is the first reported case in which the angiographic, pneumoencephalographic, nuclear scan and CAT data have been correlated. In this case the CAT scan proved the most sensitive in the demonstration of tumor.", "contents": "Cerebellar glioblastoma multiforme in an adult. One of the few well documented cases of cerebellar glioblastoma multiforme in an adult is reported. In addition, to our knowledge, it is the first reported case in which the angiographic, pneumoencephalographic, nuclear scan and CAT data have been correlated. In this case the CAT scan proved the most sensitive in the demonstration of tumor."} {"id": "PMID:180622", "title": "The Pulfrich stereo-illusion as an index of optic nerve dysfunction.", "content": "A simple test based on the Pulfrich phenomenon may provide an indication of optic nerve dysfunction. When a small object swinging pendulum fashion is viewed binocularly by a person with one eye covered by a neutral density filter, the object appears to swing in an elliptical path. The patient with optic nerve dysfunction may see it this way without use of a filter. The Pulfrich theory is explained, clinical applications are discussed, and instructions for constructing a Pulfrich apparatus are given.", "contents": "The Pulfrich stereo-illusion as an index of optic nerve dysfunction. A simple test based on the Pulfrich phenomenon may provide an indication of optic nerve dysfunction. When a small object swinging pendulum fashion is viewed binocularly by a person with one eye covered by a neutral density filter, the object appears to swing in an elliptical path. The patient with optic nerve dysfunction may see it this way without use of a filter. The Pulfrich theory is explained, clinical applications are discussed, and instructions for constructing a Pulfrich apparatus are given."} {"id": "PMID:180631", "title": "[Enzootic bovine leukaemia, diagnosis, distribution and control in the Netherlands (author's transl)].", "content": "The results of studies on the incidence of enzootic bovine leukaemia in the Netherlands from 1968 to 1975 inclusive are given. The serological methods used (fluorescent antibody technique, immunoperoxidase test, micro complement fixation test and gel diffusion test) were found to be of great value especially for the early diagnosis of the disease. Antibodies to bovine leukaemia virus are already detected long before the onset of persistent lymphocytosis. The results obtained so far with serological methods confirm earlier haematological findings that enzootic bovine leukaemia is non-existent in the Dutch Friesian-Holstein and Meuse-Rhine-IJssel breeds. The first cases of enzootic bovine leukaemia were observed in import cattle in 1970. The geographic distribution of farms exploiting import cattle in which the disease has been diagnosed is presented on chart 1. Methods used to control enzootic bovine leukaemia are briefly described.", "contents": "[Enzootic bovine leukaemia, diagnosis, distribution and control in the Netherlands (author's transl)]. The results of studies on the incidence of enzootic bovine leukaemia in the Netherlands from 1968 to 1975 inclusive are given. The serological methods used (fluorescent antibody technique, immunoperoxidase test, micro complement fixation test and gel diffusion test) were found to be of great value especially for the early diagnosis of the disease. Antibodies to bovine leukaemia virus are already detected long before the onset of persistent lymphocytosis. The results obtained so far with serological methods confirm earlier haematological findings that enzootic bovine leukaemia is non-existent in the Dutch Friesian-Holstein and Meuse-Rhine-IJssel breeds. The first cases of enzootic bovine leukaemia were observed in import cattle in 1970. The geographic distribution of farms exploiting import cattle in which the disease has been diagnosed is presented on chart 1. Methods used to control enzootic bovine leukaemia are briefly described."} {"id": "PMID:180635", "title": "Late effects in the central nervous system. A study of biochemical alterations after local exposure of the rat brain to 2 krd.", "content": "The brain area of female rats three months of age was exposed to 2 krd of X-rays, and various biochemical parameters were retermined as well as NAD(H) in vivo fluorescence of the brain surface after time intervals from one day to 18 months. During the early period, an increase in the uptake of alpha-aminobutyrate (AIB) and a temporary depression in beta-glucuronidase and cathepsin activity followed by an activation at one month was seen. Somewhat later, acid phosphatase increases. During the intermediate period, DNA and serotonin content and AIB uptake by brain increase, whereas AIB uptake by heart and muscle decreases. A fall in sialic acid content is also noted at this time. During the late phase collagen increases, AIB uptake by brain and liver decreases. No changes were found with respect to NAD(H) fluorescence and its response to breathing of low oxygen concentrations.", "contents": "Late effects in the central nervous system. A study of biochemical alterations after local exposure of the rat brain to 2 krd. The brain area of female rats three months of age was exposed to 2 krd of X-rays, and various biochemical parameters were retermined as well as NAD(H) in vivo fluorescence of the brain surface after time intervals from one day to 18 months. During the early period, an increase in the uptake of alpha-aminobutyrate (AIB) and a temporary depression in beta-glucuronidase and cathepsin activity followed by an activation at one month was seen. Somewhat later, acid phosphatase increases. During the intermediate period, DNA and serotonin content and AIB uptake by brain increase, whereas AIB uptake by heart and muscle decreases. A fall in sialic acid content is also noted at this time. During the late phase collagen increases, AIB uptake by brain and liver decreases. No changes were found with respect to NAD(H) fluorescence and its response to breathing of low oxygen concentrations."} {"id": "PMID:180639", "title": "Possibilities and limitations of ultrasonic diagnosis of space occupying lesions in internal medicine.", "content": "Possibilities and limitations of ultrasonic tumour diagnosis in internal medicine (thyroid gland, liver, pancreas, kidney, malignant lymphomas) are discussed on the basis of a five years experience with about 4,000 examinations a year. A real time and gray-scale technique is used. The accuracy of the presented ultrasonic findings is proven by comparative studies. Besides the well known advantages of ultrasonography the independence from contrast medias must be stressed in comparison to diagnostic radiology. The main limitations of ultrasonography are the impossibility of diagnosing tumours smaller than 1.5-2 cm and the absence of an ultrasonic pattern typical of malignancy. To establish a morphobiological diagnosis, ultrasonically guided fine needle biopsy has proved to be a reliable method.", "contents": "Possibilities and limitations of ultrasonic diagnosis of space occupying lesions in internal medicine. Possibilities and limitations of ultrasonic tumour diagnosis in internal medicine (thyroid gland, liver, pancreas, kidney, malignant lymphomas) are discussed on the basis of a five years experience with about 4,000 examinations a year. A real time and gray-scale technique is used. The accuracy of the presented ultrasonic findings is proven by comparative studies. Besides the well known advantages of ultrasonography the independence from contrast medias must be stressed in comparison to diagnostic radiology. The main limitations of ultrasonography are the impossibility of diagnosing tumours smaller than 1.5-2 cm and the absence of an ultrasonic pattern typical of malignancy. To establish a morphobiological diagnosis, ultrasonically guided fine needle biopsy has proved to be a reliable method."} {"id": "PMID:180640", "title": "Functioning malignant nonchromaffin paraganglioma of retroperitoneum with metastases.", "content": "A case is reported of a functioning, malignant nonchromaffin paraganglioma (chemodectoma) of the retroperitoneum with metastases in a seventeen-year-old boy. The literature is reviewed and the treatment modalities are discussed.", "contents": "Functioning malignant nonchromaffin paraganglioma of retroperitoneum with metastases. A case is reported of a functioning, malignant nonchromaffin paraganglioma (chemodectoma) of the retroperitoneum with metastases in a seventeen-year-old boy. The literature is reviewed and the treatment modalities are discussed."} {"id": "PMID:180638", "title": "[Induction of cell differentiation by ACTH in a monolayer culture of human fetal adrenal glands].", "content": "Investigations carried out testified to the fact that fibroblast-like cells in the monolayer culture of the human fetus adrenal glands are heterogenic. Under the effect of ACTH physiological doses nearly all of them are differentiated into specialized hormone-producing cells, the rest part - into fibroblasts.", "contents": "[Induction of cell differentiation by ACTH in a monolayer culture of human fetal adrenal glands]. Investigations carried out testified to the fact that fibroblast-like cells in the monolayer culture of the human fetus adrenal glands are heterogenic. Under the effect of ACTH physiological doses nearly all of them are differentiated into specialized hormone-producing cells, the rest part - into fibroblasts."} {"id": "PMID:180643", "title": "[Dynamics of changes in the activity of plasma lactate dehydrogenase, leucylarylamidase and GOT and GPT aminotransferases in poultry following damage to the organism caused by cadmium and tetrachloromethane].", "content": "In the experiments performed with broilers, after a per os application of tetrachloromethane and cadmium (Cd+2), the activity of lactate dehydrogenase (LDH), leucylarylamidase (LA), and the GOT and GPT amino transferase was determined in the blood plasm. By means of an electrophoretic division of the blood plasm of clinically healthy broilers one enzymatically active fraction of LA and LDH was ascertained. The injury caused to the organism of poultry by carbon tetrachloride and cadmium did not affect the heterogeneity of these two enzymes. After an application of tetrachloromethane (CCl4) in the dose of 8 and 10 ml kg-1 the total activity of LDH and LA changed. The influence of cadmium on the organism in the total dose of 200 mg kg-1 resulted in the changed activity of LDH, GOT, and LA. From the results obtained it has been assumed that the examined activity of LDH, GOT, and LA can be utilized for the diagnosing of non-specific injuries of the organism of poultry.", "contents": "[Dynamics of changes in the activity of plasma lactate dehydrogenase, leucylarylamidase and GOT and GPT aminotransferases in poultry following damage to the organism caused by cadmium and tetrachloromethane]. In the experiments performed with broilers, after a per os application of tetrachloromethane and cadmium (Cd+2), the activity of lactate dehydrogenase (LDH), leucylarylamidase (LA), and the GOT and GPT amino transferase was determined in the blood plasm. By means of an electrophoretic division of the blood plasm of clinically healthy broilers one enzymatically active fraction of LA and LDH was ascertained. The injury caused to the organism of poultry by carbon tetrachloride and cadmium did not affect the heterogeneity of these two enzymes. After an application of tetrachloromethane (CCl4) in the dose of 8 and 10 ml kg-1 the total activity of LDH and LA changed. The influence of cadmium on the organism in the total dose of 200 mg kg-1 resulted in the changed activity of LDH, GOT, and LA. From the results obtained it has been assumed that the examined activity of LDH, GOT, and LA can be utilized for the diagnosing of non-specific injuries of the organism of poultry."} {"id": "PMID:180644", "title": "[Marek's disease--characterization of the VUB-70 strain in vivo].", "content": "In the course of serial passaging of the strain of Marek's disease (MD) (VUB-70) in White Leghorns the author investigated the morbidity, mortality, development of the MD-specific changes, and the effect of sex on these indices, for the purpose of characterization of the biological properties of an isolated strain of MD in vivo. The incubation period lasted from 41 to 46 days p. inf. on the first day of life. Pullets showed greater sensitiveness towards infection not only through higher morbidity and mortality, but also due to a larger number of tumorous changes. In MD-positive animals the same proportion of macroscopic and microscopic changes was found. The average occurrence of Marek's disease amounted to 74.4 p. c. On the basis of the biological properties in vivo the VUB-70 strain was characterized as a medium pathogenic strain of the acute form of Marek's disease.", "contents": "[Marek's disease--characterization of the VUB-70 strain in vivo]. In the course of serial passaging of the strain of Marek's disease (MD) (VUB-70) in White Leghorns the author investigated the morbidity, mortality, development of the MD-specific changes, and the effect of sex on these indices, for the purpose of characterization of the biological properties of an isolated strain of MD in vivo. The incubation period lasted from 41 to 46 days p. inf. on the first day of life. Pullets showed greater sensitiveness towards infection not only through higher morbidity and mortality, but also due to a larger number of tumorous changes. In MD-positive animals the same proportion of macroscopic and microscopic changes was found. The average occurrence of Marek's disease amounted to 74.4 p. c. On the basis of the biological properties in vivo the VUB-70 strain was characterized as a medium pathogenic strain of the acute form of Marek's disease."} {"id": "PMID:180645", "title": "Pathogenesis of digestive tract lesions in duck plague.", "content": "White Pekin ducklings were inoculated orally with duck plague virus. Tissues from the digestive tract were collected daily after inoculation and examined by light, electron and fluorescent microscopy. There were necrosis and degeneration of stratified squamous epithelium of the esophagus and cloaca, epithelium of intestinal crypt and esophageal submucosal glands, macrophages in the lamina propria, and submucosal fibrocytes and lymphocytes. Submucosal hemorrhages occurred after degeneration and necrosis of lymphocytes, macrophages, fibrocytes and epithelial cells. Viral antigens were detected in all these cells by use of fluorescein-labeled antibodies. With the electron microscope, nucleocapsids were seen in the nuclei, budding through the inner nuclear membrane; enveloped virions were present in cytoplasmic vacuoles of macrophages, epithelial cells and fibrocytes. In lymphocytes, nucleocapsids were also in the nuclei, but karyorrhexis and cytolysis occurred before viral maturation was completed.", "contents": "Pathogenesis of digestive tract lesions in duck plague. White Pekin ducklings were inoculated orally with duck plague virus. Tissues from the digestive tract were collected daily after inoculation and examined by light, electron and fluorescent microscopy. There were necrosis and degeneration of stratified squamous epithelium of the esophagus and cloaca, epithelium of intestinal crypt and esophageal submucosal glands, macrophages in the lamina propria, and submucosal fibrocytes and lymphocytes. Submucosal hemorrhages occurred after degeneration and necrosis of lymphocytes, macrophages, fibrocytes and epithelial cells. Viral antigens were detected in all these cells by use of fluorescein-labeled antibodies. With the electron microscope, nucleocapsids were seen in the nuclei, budding through the inner nuclear membrane; enveloped virions were present in cytoplasmic vacuoles of macrophages, epithelial cells and fibrocytes. In lymphocytes, nucleocapsids were also in the nuclei, but karyorrhexis and cytolysis occurred before viral maturation was completed."} {"id": "PMID:180646", "title": "Ultrastructural changes in bovine lingual epithelium infected with vesicular stomatitis virus.", "content": "Vesicular stomatitis virus was inoculated into the dorsal lingual epithelium of three cows. The reaction that developed in 72 h was characterized by severe acute diffuse glossitis with intercellular edema and necrosis of keratinocytes. Virions budded from the plasma membrane and were in the intercellular spaces. Reduplication of desmosomes was a prominent alteration, and normal desmosomes were within the cytoplasm. Intracytoplasmic desmosomes appeared to be formed by endocytosis after breaks occurred in the plasma membrane of one cell; endocytosis of loops of plasma membrane containing desmosomes; and formation of desmosomes on invagination of the plasma membrane.", "contents": "Ultrastructural changes in bovine lingual epithelium infected with vesicular stomatitis virus. Vesicular stomatitis virus was inoculated into the dorsal lingual epithelium of three cows. The reaction that developed in 72 h was characterized by severe acute diffuse glossitis with intercellular edema and necrosis of keratinocytes. Virions budded from the plasma membrane and were in the intercellular spaces. Reduplication of desmosomes was a prominent alteration, and normal desmosomes were within the cytoplasm. Intracytoplasmic desmosomes appeared to be formed by endocytosis after breaks occurred in the plasma membrane of one cell; endocytosis of loops of plasma membrane containing desmosomes; and formation of desmosomes on invagination of the plasma membrane."} {"id": "PMID:180647", "title": "Neuromuscular lesions in restrained rabbits.", "content": "Ten of 16 rabbits restrained 6 h daily for 35 days developed focal to diffuse degeneration of the sciatic nerves. Very small necrotic areas also were found in the skeletal muscles of seven of 16 rabbits, but the muscle lesions did not correlate with the nerve changes.", "contents": "Neuromuscular lesions in restrained rabbits. Ten of 16 rabbits restrained 6 h daily for 35 days developed focal to diffuse degeneration of the sciatic nerves. Very small necrotic areas also were found in the skeletal muscles of seven of 16 rabbits, but the muscle lesions did not correlate with the nerve changes."} {"id": "PMID:180648", "title": "Feline intestinal adenocarcinoma. A clinicopathologic study of 22 cases.", "content": "Twenty-two cases of intestinal adenocarcinoma were diagnosed in an 11-year survey of 3145 feline necropsies. Histologically, tumors were grouped into four classes: (1) carcinoma with solid groups of cells, (2) adenocarcinoma with solid and acinar cells, (3) papillary adenocarcinoma, and (4) mucinous adenocarcinoma. Tumors were commonest in the ileum. Connective tissue, as well as epithelial metaplasia, were associated more often in this group of intestinal adenocarcinomas nomas than seen before. Hypertrophy and hyperplasia of muscular layers of the unaffected sections of intestines were seen in most of the small bowel and in half of the large bowel carcinomas in this series.", "contents": "Feline intestinal adenocarcinoma. A clinicopathologic study of 22 cases. Twenty-two cases of intestinal adenocarcinoma were diagnosed in an 11-year survey of 3145 feline necropsies. Histologically, tumors were grouped into four classes: (1) carcinoma with solid groups of cells, (2) adenocarcinoma with solid and acinar cells, (3) papillary adenocarcinoma, and (4) mucinous adenocarcinoma. Tumors were commonest in the ileum. Connective tissue, as well as epithelial metaplasia, were associated more often in this group of intestinal adenocarcinomas nomas than seen before. Hypertrophy and hyperplasia of muscular layers of the unaffected sections of intestines were seen in most of the small bowel and in half of the large bowel carcinomas in this series."} {"id": "PMID:180649", "title": "Naturally-occurring Sendai virus infection of athymic nude mice.", "content": "Nude (nu/nu) mice, Balb/c-derived, responded to a naturally-occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia.", "contents": "Naturally-occurring Sendai virus infection of athymic nude mice. Nude (nu/nu) mice, Balb/c-derived, responded to a naturally-occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia."} {"id": "PMID:180650", "title": "Meningoencephalomyelitis in horses associated with equine herpesvirus 1 infection.", "content": "During an outbreak of abortion caused by equine herpesvirus 1, a neurologic disease characterized clinically by dullness and ataxia occurred in several mares. Equine herpesvirus 1 was isolated from brain and lung of two severely affected mares. Histologically, both mares had disseminated meningoencephalomyelitis characterized by necrotizing arteritis, focal malacia in grey and white matter of brain and spinal cord, and accumulation of lymphocytes and neutrophils in paravertebral ganglia. Eosinophilic intranuclear inclusion bodies occurred in foci of necrosis in thyroid adenomas of both mares.", "contents": "Meningoencephalomyelitis in horses associated with equine herpesvirus 1 infection. During an outbreak of abortion caused by equine herpesvirus 1, a neurologic disease characterized clinically by dullness and ataxia occurred in several mares. Equine herpesvirus 1 was isolated from brain and lung of two severely affected mares. Histologically, both mares had disseminated meningoencephalomyelitis characterized by necrotizing arteritis, focal malacia in grey and white matter of brain and spinal cord, and accumulation of lymphocytes and neutrophils in paravertebral ganglia. Eosinophilic intranuclear inclusion bodies occurred in foci of necrosis in thyroid adenomas of both mares."} {"id": "PMID:180651", "title": "Glomerulonephritis caused by murine cytomegalovirus. Potentiation by antithymocyte serum.", "content": "Murine cytomegalovirus was found to be highly nephrotropic in mice treated with antithymocyte serum. The earliest histologic change was characteristic intranuclear inclusions in the glomerular endothelial cells. This change was followed by an eosinophilic thickening of the glomerular capillary loops. In later stages, proliferation of capsular epithelial cells and glomerular sclerosis was prominent. Tubular casts were present, and perivascular lymphoid aggregations were seen in the medulla and juxtamedullary section 56 days after inoculation. No conspicuous lesions occurred in uninfected mice treated with antithymocyte serum or in untreated infected mice. The possible mechanisms of the renal lesions are discussed.", "contents": "Glomerulonephritis caused by murine cytomegalovirus. Potentiation by antithymocyte serum. Murine cytomegalovirus was found to be highly nephrotropic in mice treated with antithymocyte serum. The earliest histologic change was characteristic intranuclear inclusions in the glomerular endothelial cells. This change was followed by an eosinophilic thickening of the glomerular capillary loops. In later stages, proliferation of capsular epithelial cells and glomerular sclerosis was prominent. Tubular casts were present, and perivascular lymphoid aggregations were seen in the medulla and juxtamedullary section 56 days after inoculation. No conspicuous lesions occurred in uninfected mice treated with antithymocyte serum or in untreated infected mice. The possible mechanisms of the renal lesions are discussed."} {"id": "PMID:180652", "title": "Disseminated necrotizing myeloencephalitis: a herpes-associated neurological disease of horses.", "content": "Equine viral rhinopneumonitis type I virus was isolated from spinal cord and brain of a paraparetic horse with disseminated necrotizing myeloencephalitis. Necrotic arteriolitis,nonsuppurative necrotizing myeloencephalitis and Gasserian ganglioneuritis were present. On record were 12 more cases of horses with similar lesions. The horses had been ataxic or paretic for up to several weeks. A field survey indicated that 14 of 24 horses with acute myelitic signs developed them after recent exposure to respiratory disease.", "contents": "Disseminated necrotizing myeloencephalitis: a herpes-associated neurological disease of horses. Equine viral rhinopneumonitis type I virus was isolated from spinal cord and brain of a paraparetic horse with disseminated necrotizing myeloencephalitis. Necrotic arteriolitis,nonsuppurative necrotizing myeloencephalitis and Gasserian ganglioneuritis were present. On record were 12 more cases of horses with similar lesions. The horses had been ataxic or paretic for up to several weeks. A field survey indicated that 14 of 24 horses with acute myelitic signs developed them after recent exposure to respiratory disease."} {"id": "PMID:180653", "title": "Gnotobiotic piglets experimentally infected with neonatal calf diarrhoea reovirus-like agent (Rotavirus).", "content": "Gnotobiotic piglets were infected with a strain of rotavirus that had been isolated from a calf and passaged four times in piglets. The resulting disease was studied by light and electron microscopy at 21, 44 and 68 h after inoculation. In the small intestine infection caused desquamation of the epithelial cells of the villi resulting in severe stunting. There was severe damage to microvilli and accumulation of lipid within the cytoplasm. Virus particles were seen in epithelial cells covering the stunted villi. Infection also caused desquamation of the superficial epithelial cells of the stomach mucosa and of the epithelial cells of the bronchi, bronchioles, and alveoli of the lungs.", "contents": "Gnotobiotic piglets experimentally infected with neonatal calf diarrhoea reovirus-like agent (Rotavirus). Gnotobiotic piglets were infected with a strain of rotavirus that had been isolated from a calf and passaged four times in piglets. The resulting disease was studied by light and electron microscopy at 21, 44 and 68 h after inoculation. In the small intestine infection caused desquamation of the epithelial cells of the villi resulting in severe stunting. There was severe damage to microvilli and accumulation of lipid within the cytoplasm. Virus particles were seen in epithelial cells covering the stunted villi. Infection also caused desquamation of the superficial epithelial cells of the stomach mucosa and of the epithelial cells of the bronchi, bronchioles, and alveoli of the lungs."} {"id": "PMID:180655", "title": "Intranuclear inclusions in a myopathy of late onset.", "content": "Filamentous intranuclear inclusions in a case of myopathy of late onset are described. The filaments were usually in parallel array although occasionally they were haphazardly arranged in bundles ranging up to 5 mu in length. The filaments were approximately 120 A in diameter and were separated by a space measuring 180-220 A. Possible explanations of their occurrence in the nucleoplasm are discussed, including possible origin from the cytoplasm as a result of invagination of nuclear membrane and intranuclear entrapment of myofibrils from the cytoplasm. Their appearance does not suggest any recognizable structure such as myofilaments or virus. It is possible that the filaments are protein newly synthesized as a direct result of virus infection with invasion of the nuclei of the muscle cell.", "contents": "Intranuclear inclusions in a myopathy of late onset. Filamentous intranuclear inclusions in a case of myopathy of late onset are described. The filaments were usually in parallel array although occasionally they were haphazardly arranged in bundles ranging up to 5 mu in length. The filaments were approximately 120 A in diameter and were separated by a space measuring 180-220 A. Possible explanations of their occurrence in the nucleoplasm are discussed, including possible origin from the cytoplasm as a result of invagination of nuclear membrane and intranuclear entrapment of myofibrils from the cytoplasm. Their appearance does not suggest any recognizable structure such as myofilaments or virus. It is possible that the filaments are protein newly synthesized as a direct result of virus infection with invasion of the nuclei of the muscle cell."} {"id": "PMID:180656", "title": "Lamellated bodies in the neurons of the submucosal ganglia in the sphincter of Oddi of the dog.", "content": "Peculiar neurons and nerve processes, which contained remarkable amounts of lamellated, electron-dense bodies, \"myeloid bodies\", are described. They were found among normal looking neurons in the submucosal ganglia of the sphincteric musculature of Oddi. The innervation and ultrastructure of the ganglia were studied in apparently healthy, young dogs bred for experimental purposes. The possible function of these neurons and processes is discussed.", "contents": "Lamellated bodies in the neurons of the submucosal ganglia in the sphincter of Oddi of the dog. Peculiar neurons and nerve processes, which contained remarkable amounts of lamellated, electron-dense bodies, \"myeloid bodies\", are described. They were found among normal looking neurons in the submucosal ganglia of the sphincteric musculature of Oddi. The innervation and ultrastructure of the ganglia were studied in apparently healthy, young dogs bred for experimental purposes. The possible function of these neurons and processes is discussed."} {"id": "PMID:180684", "title": "[Radiation therapy of patients with inoperable cancer of the pancreas].", "content": "Radiotherapy was employed in 60 patients, symptomatic treatment--in 10 patients with pancreatic cancer, 9 of them had the disease in stage III. Radiotherapy, using betatron 25 Mev, was conducted by a longitudinal method, distant gammatherapy--through a wolfram and the radiation source focused grid. Single focal dosage was 150--200 rad, total--5000--8000 rad. The treatment proved to be uneffective in 31.7 per cent of patients.", "contents": "[Radiation therapy of patients with inoperable cancer of the pancreas]. Radiotherapy was employed in 60 patients, symptomatic treatment--in 10 patients with pancreatic cancer, 9 of them had the disease in stage III. Radiotherapy, using betatron 25 Mev, was conducted by a longitudinal method, distant gammatherapy--through a wolfram and the radiation source focused grid. Single focal dosage was 150--200 rad, total--5000--8000 rad. The treatment proved to be uneffective in 31.7 per cent of patients."} {"id": "PMID:180688", "title": "[Experimental data on the virological study of pasteurized milk].", "content": "Virological analyses of sterile milk per se enabled the poliovirus to be disclosed with a concentration of 30 infection units in 1 ml. To determine such doses of the viruses in pasteurized milk the viruses have to be concentrated, for prior to cytopathogenic manifestations subsequent to these viral doses there occurs bacterial germination. In achieving poliovirus concentration in pasteurized milk are suitable polyethyleneglycol, molecular weight 15 000, and polyvinylpyrolidon, molecular weight 10 000, in a 10% concentration. Dilution of milk with Hanks' solution in the ratio of 1:4 and 1:9 improves the process of the poliovirus sorption-eluation with the polymer, enabling it to detect 3 BOU of the virus in 1 ml of milk. The AB-17-8 anionite and Ky-21-8 cationite are capable of adequately sorbing the poliovirus in pasteurized milk, but it is only from the cationite, and then only in a small amount, that eluation of the virus can be accomplished.", "contents": "[Experimental data on the virological study of pasteurized milk]. Virological analyses of sterile milk per se enabled the poliovirus to be disclosed with a concentration of 30 infection units in 1 ml. To determine such doses of the viruses in pasteurized milk the viruses have to be concentrated, for prior to cytopathogenic manifestations subsequent to these viral doses there occurs bacterial germination. In achieving poliovirus concentration in pasteurized milk are suitable polyethyleneglycol, molecular weight 15 000, and polyvinylpyrolidon, molecular weight 10 000, in a 10% concentration. Dilution of milk with Hanks' solution in the ratio of 1:4 and 1:9 improves the process of the poliovirus sorption-eluation with the polymer, enabling it to detect 3 BOU of the virus in 1 ml of milk. The AB-17-8 anionite and Ky-21-8 cationite are capable of adequately sorbing the poliovirus in pasteurized milk, but it is only from the cationite, and then only in a small amount, that eluation of the virus can be accomplished."} {"id": "PMID:180693", "title": "[Obesity in correlation with nutrition in representative settlements of the industrial-agrarian complex in Burgas].", "content": "The authors investigated the obesity incidence in connection with nutrition factors in 13 representative settlements of Industry-Agrarian Complex Burgas. They established that obesity covers 42,4 per cent of the population above the age of 14 and is 1,5 times more often among females as compared with males. The correlation among youths (age 14-25), mature aged subjects (26-50) and advanced aged ones (over 51) is 1:5,5:4,5. The light I and II stages prevail (88,6 per cent of all the cases) and the majority of the \"pure\" cases of obesity (73,6 per cent) have no complains.", "contents": "[Obesity in correlation with nutrition in representative settlements of the industrial-agrarian complex in Burgas]. The authors investigated the obesity incidence in connection with nutrition factors in 13 representative settlements of Industry-Agrarian Complex Burgas. They established that obesity covers 42,4 per cent of the population above the age of 14 and is 1,5 times more often among females as compared with males. The correlation among youths (age 14-25), mature aged subjects (26-50) and advanced aged ones (over 51) is 1:5,5:4,5. The light I and II stages prevail (88,6 per cent of all the cases) and the majority of the \"pure\" cases of obesity (73,6 per cent) have no complains."} {"id": "PMID:180690", "title": "[Immunologic study of suspension cultures prepared from hematopoietic organ cells of baboons with lymphoma].", "content": "The cytoplasmic antigen was determined by the indirect immunofluorescence test using serum from a Burkitt lymphoma patient with a titer of antibody to Epstein-Barr virus capsid antigen of 1.320, in the cytoplasm of 2--6% of cells of suspension cultures obtained from baboons with lymphoma. There was a correlation between the number of antigen-containing cells in this cultures and the number of cells in which herpes virus was determined by electron microscope studies. Sera from baboons with lymphoma from which the suspensions cultures had been prepared contained high titers of antibody to herpes virus of baboons (HVB) and to Epstein-Barr virus (EBV). Specific differences between the antigens produced in the cultures by HVB and EBV were minimal, indicating their immunological similarity. Lymphoblastoid cultures prepared from hemopoietic organs of baboons with lymphoma belong to B cell type.", "contents": "[Immunologic study of suspension cultures prepared from hematopoietic organ cells of baboons with lymphoma]. The cytoplasmic antigen was determined by the indirect immunofluorescence test using serum from a Burkitt lymphoma patient with a titer of antibody to Epstein-Barr virus capsid antigen of 1.320, in the cytoplasm of 2--6% of cells of suspension cultures obtained from baboons with lymphoma. There was a correlation between the number of antigen-containing cells in this cultures and the number of cells in which herpes virus was determined by electron microscope studies. Sera from baboons with lymphoma from which the suspensions cultures had been prepared contained high titers of antibody to herpes virus of baboons (HVB) and to Epstein-Barr virus (EBV). Specific differences between the antigens produced in the cultures by HVB and EBV were minimal, indicating their immunological similarity. Lymphoblastoid cultures prepared from hemopoietic organs of baboons with lymphoma belong to B cell type."} {"id": "PMID:180691", "title": "[Effect of 2-deoxy-d-glucose on enterovirus reproduction in HEp-2 cell cultures].", "content": "The influence of 2-deoxy-d-glucose (2DG) on reproduction of some enteroviruses was studied. When 2DG was added to carbohydrate-free medium. It exerted a marked inhibiting effect on reproduction of poliovirus type I (virulent and attenuated variants) and Coxsackie B1, B2, B3, B5 and B6 viruses. The agent was inactive for virulent and attenuated poliomyelitis type II viruses. Poliomyelitis type III and Coxsackie B4 viruses were shown to be incable of multiplication in carbohydrate-free medium when the maintenance medium in cell cultures was lactalbumin hydrolysate in Hank's solution without-glucose. The inhibiting effect of 2DG on sensitive enteroviruses was irreversible and manifest at a concentration as low as 0.1 mg/ml. The effect of the agent was directed to the active stages of intracellular enterovirus synthesis. The possible mechanism of inhibition of enterovirus reproduction in the presence of 2DG is discussed.", "contents": "[Effect of 2-deoxy-d-glucose on enterovirus reproduction in HEp-2 cell cultures]. The influence of 2-deoxy-d-glucose (2DG) on reproduction of some enteroviruses was studied. When 2DG was added to carbohydrate-free medium. It exerted a marked inhibiting effect on reproduction of poliovirus type I (virulent and attenuated variants) and Coxsackie B1, B2, B3, B5 and B6 viruses. The agent was inactive for virulent and attenuated poliomyelitis type II viruses. Poliomyelitis type III and Coxsackie B4 viruses were shown to be incable of multiplication in carbohydrate-free medium when the maintenance medium in cell cultures was lactalbumin hydrolysate in Hank's solution without-glucose. The inhibiting effect of 2DG on sensitive enteroviruses was irreversible and manifest at a concentration as low as 0.1 mg/ml. The effect of the agent was directed to the active stages of intracellular enterovirus synthesis. The possible mechanism of inhibition of enterovirus reproduction in the presence of 2DG is discussed."} {"id": "PMID:180692", "title": "[Comparative antigenic analysis of J-96 cell oncornavirus and Mason-Pfizer virus from a spontaneous monkey mammary tumor].", "content": "A comparative study of the antigenic structure of oncornavirus of J-96 cells and Mason-Pfizer virus (M-PVM) isolated from cells of M. rhesus spontaneous mammary tumour was carried out using immunodiffusion in agar, immune autoradiography and indirect immunofluorescence procedures. Immune rabbit serum to disrupted J-96 virus detected by agar immunodiffusion in preparations or purified virus three soluble antigens one of which was identical to group-specific M-PVM antigen.", "contents": "[Comparative antigenic analysis of J-96 cell oncornavirus and Mason-Pfizer virus from a spontaneous monkey mammary tumor]. A comparative study of the antigenic structure of oncornavirus of J-96 cells and Mason-Pfizer virus (M-PVM) isolated from cells of M. rhesus spontaneous mammary tumour was carried out using immunodiffusion in agar, immune autoradiography and indirect immunofluorescence procedures. Immune rabbit serum to disrupted J-96 virus detected by agar immunodiffusion in preparations or purified virus three soluble antigens one of which was identical to group-specific M-PVM antigen."} {"id": "PMID:180698", "title": "[The clinical significance of the radioimmunological determination of plasma ACTH (author's transl)].", "content": "The clinical significance of the direct determination of plasma ACTH was investigated in healthy persons and in patients with primary or secondary adrenocortical insufficiency, with Cushing's syndrome or with acromegaly. The sensitivity of the radioimmunological method facilitated the detection of diurnal changes in plasma ACTH in healthy subjects and of variations in plasma ACTH after the administration of dexamethasone and glucagon. The determination of plasma ACTH appears to be a useful procedure of diagnostic value in patients suffering from primary adrenal insufficiency accompanied by high concentrations of plasma ACTH. However, in patients suffering from Cushing's syndrome or secondary adrenocortical insufficiency it is still essential to carry out the dexamethasone suppression test or the metopiron test, respectively.", "contents": "[The clinical significance of the radioimmunological determination of plasma ACTH (author's transl)]. The clinical significance of the direct determination of plasma ACTH was investigated in healthy persons and in patients with primary or secondary adrenocortical insufficiency, with Cushing's syndrome or with acromegaly. The sensitivity of the radioimmunological method facilitated the detection of diurnal changes in plasma ACTH in healthy subjects and of variations in plasma ACTH after the administration of dexamethasone and glucagon. The determination of plasma ACTH appears to be a useful procedure of diagnostic value in patients suffering from primary adrenal insufficiency accompanied by high concentrations of plasma ACTH. However, in patients suffering from Cushing's syndrome or secondary adrenocortical insufficiency it is still essential to carry out the dexamethasone suppression test or the metopiron test, respectively."} {"id": "PMID:180699", "title": "[Morphological aspects of organic brain syndromes (author's transl)].", "content": "Organic psychoses are caused by a variety of disorders. In general, they are due to diffuse dysfunction of the brain without any specific anatomical basis, but they may be modified by disorders of some distinct neuronal systems as a result of local accentuation of a dissuse morbid process or localized brain damage. Acute organic psychoses are usually caused by disorders of the blood-brain barrier (cerebral oedema), acute neuronal dysfunction of disorders of synaptic transmission. Acute lesions may be reversible or terminate in stationary defective states or progressive neuronal degeneration. In late stages, the anatomical sequelae of the basic process and of secondary lesions are hardly to be separated. The non-specificity and inconsistency of brain lesions is demonstrated in chronic alcoholic psychoses. In senile organic psychoses there are quantitative correlations between psychopathological, neurophysiological (slowing of the basic rhythm) and morphological changes, mainly characterized by loss of neurons and synaptic contacts. Vascular syndromes are often over-diagnosed clinically. Localized mental syndromes are non-specific, but show characteristic locations, as they are commonly associated with dysfunction of neuronal systems engaged in storing and recall of information (frontobasal region and limbic system). Further detailed studies are needed in order to achieve better correlation between specific features of behavioural and intellectual defects and anatomical location and quantitiy of lesions.", "contents": "[Morphological aspects of organic brain syndromes (author's transl)]. Organic psychoses are caused by a variety of disorders. In general, they are due to diffuse dysfunction of the brain without any specific anatomical basis, but they may be modified by disorders of some distinct neuronal systems as a result of local accentuation of a dissuse morbid process or localized brain damage. Acute organic psychoses are usually caused by disorders of the blood-brain barrier (cerebral oedema), acute neuronal dysfunction of disorders of synaptic transmission. Acute lesions may be reversible or terminate in stationary defective states or progressive neuronal degeneration. In late stages, the anatomical sequelae of the basic process and of secondary lesions are hardly to be separated. The non-specificity and inconsistency of brain lesions is demonstrated in chronic alcoholic psychoses. In senile organic psychoses there are quantitative correlations between psychopathological, neurophysiological (slowing of the basic rhythm) and morphological changes, mainly characterized by loss of neurons and synaptic contacts. Vascular syndromes are often over-diagnosed clinically. Localized mental syndromes are non-specific, but show characteristic locations, as they are commonly associated with dysfunction of neuronal systems engaged in storing and recall of information (frontobasal region and limbic system). Further detailed studies are needed in order to achieve better correlation between specific features of behavioural and intellectual defects and anatomical location and quantitiy of lesions."} {"id": "PMID:180705", "title": "Induction of tumors in the stomach and nervous system of the ACI/N rat by continuous oral administration of 1-methyl-3-acetyl-1-nitrosourea.", "content": "Three groups of ACI/N rats of both sexes received continuous administration of 66 (Group I), 30 Group II), or 13(Group III) ppm solution of 1-methyl-3-acetyl-1-nitrosourea (Ac-MNU) in their drinking water. Tumors were found most frequently in the stomach and nervous system. The former was more frequently found in the male than in the female. The incidence was highest in males of Group II, 28/30 (93%), and lowest in females of Group I, 4/30 (13%). Histologically, all epithelial tumors of the stomach were benign adenomas except 5 adenocarcinomas. Neurogenous tumors were more frequently seen in the female than in the male. The incidence was highest in females of Group I, 29/30 (97%), and lowest in males of Group III, 6/28 (21%). The tumors were predominant in the central nervous system, especially in the hemispheres. Transplantation studies were done in some of these tumors. Although gastric tumors failed to get positive transplantation, all the neurogenous tumors transplanted were positive.", "contents": "Induction of tumors in the stomach and nervous system of the ACI/N rat by continuous oral administration of 1-methyl-3-acetyl-1-nitrosourea. Three groups of ACI/N rats of both sexes received continuous administration of 66 (Group I), 30 Group II), or 13(Group III) ppm solution of 1-methyl-3-acetyl-1-nitrosourea (Ac-MNU) in their drinking water. Tumors were found most frequently in the stomach and nervous system. The former was more frequently found in the male than in the female. The incidence was highest in males of Group II, 28/30 (93%), and lowest in females of Group I, 4/30 (13%). Histologically, all epithelial tumors of the stomach were benign adenomas except 5 adenocarcinomas. Neurogenous tumors were more frequently seen in the female than in the male. The incidence was highest in females of Group I, 29/30 (97%), and lowest in males of Group III, 6/28 (21%). The tumors were predominant in the central nervous system, especially in the hemispheres. Transplantation studies were done in some of these tumors. Although gastric tumors failed to get positive transplantation, all the neurogenous tumors transplanted were positive."} {"id": "PMID:180706", "title": "Histophysiologic response of the pituitary-inertrenal system to salicylate and adrenocorticotropin in catfish, Heteropneustes iossilis (Bloch).", "content": "The interrenal and pituitary cells showed increase in nuclear diameter eight days after treatment with ACTH, salicylate or salicylate + ACTH. After ACTH treatment, however, the cytoplasm in the interrenal cells was granular. Similarly, the lead-haematoxylin positive (PbH + ve) cells in the rostral pars distalis also showed partial depletion of stainable granules after ACTH treatment. Salicylate or salicylate ACTH caused depletion of cytoplasmic material in both the interrenal as well as PbH + ve cells.", "contents": "Histophysiologic response of the pituitary-inertrenal system to salicylate and adrenocorticotropin in catfish, Heteropneustes iossilis (Bloch). The interrenal and pituitary cells showed increase in nuclear diameter eight days after treatment with ACTH, salicylate or salicylate + ACTH. After ACTH treatment, however, the cytoplasm in the interrenal cells was granular. Similarly, the lead-haematoxylin positive (PbH + ve) cells in the rostral pars distalis also showed partial depletion of stainable granules after ACTH treatment. Salicylate or salicylate ACTH caused depletion of cytoplasmic material in both the interrenal as well as PbH + ve cells."} {"id": "PMID:180707", "title": "Effect of ACTH and bilateral gonadectomy on the adrenocortical tissue of an air-breathing fish -- Heteropneustes fossilis (Bloch).", "content": "The mammalian ACTH (20 I.U.) injected in Heteropneustes fossilis (Bloch) caused hyperplasia of the adrenocortical tissue. The interrenal as well as chrome cells became vacuolated. The interrenal nuclear size increased by 15% as an average than the control fishes. The glycogen granules were found to be absent from the interrenal cells. The effect of bilateral gonadectomy in both sexes has been marked in the gradual decrease of the interrenal nuclear diameter which 12 weeks after the operation, recorded nearly 25% reduction in size. The glycogen content was reduced considerably. Removal of gonads during maturation period bringing inhibition of hyperplasia of the gland at the time of spawning possibly indicates action of gonadal steroids on the physiological alterations of the interrenal cells.", "contents": "Effect of ACTH and bilateral gonadectomy on the adrenocortical tissue of an air-breathing fish -- Heteropneustes fossilis (Bloch). The mammalian ACTH (20 I.U.) injected in Heteropneustes fossilis (Bloch) caused hyperplasia of the adrenocortical tissue. The interrenal as well as chrome cells became vacuolated. The interrenal nuclear size increased by 15% as an average than the control fishes. The glycogen granules were found to be absent from the interrenal cells. The effect of bilateral gonadectomy in both sexes has been marked in the gradual decrease of the interrenal nuclear diameter which 12 weeks after the operation, recorded nearly 25% reduction in size. The glycogen content was reduced considerably. Removal of gonads during maturation period bringing inhibition of hyperplasia of the gland at the time of spawning possibly indicates action of gonadal steroids on the physiological alterations of the interrenal cells."} {"id": "PMID:180708", "title": "[The occurence of Psammom bodies in the thyroid gland of aged rats].", "content": "The author examined the thyroid glands of 52 aged (18 to 30 months old) and 14 young (6 months old) male rats with histophysiological methods. By means of light-microscopical examinations he observed laminated colloid, i.e. psammom bodies which contained calcium and iron, in the follicles of the thyroid glands of the old rats. Founding himself upon data of the literature, he deals with the questions of the occurrence and origin of the psammom bodies. Relying on his own examinations he is of the opinion that in the case of animals involution and dystrophic of a certain degree connected with senescence calls forth on oedema which and besides also the adenomas occurring in greater numbers means a disorder of the metabolic processes taking place in the thyroid gland and a possibility of the formation of psammom bodies. Eventually, in the authors opinion it cannot be stated with certainty -- at least in the case of animals -- that there is a close relationship between the occurrence of psammom bodies and the neoplasma.", "contents": "[The occurence of Psammom bodies in the thyroid gland of aged rats]. The author examined the thyroid glands of 52 aged (18 to 30 months old) and 14 young (6 months old) male rats with histophysiological methods. By means of light-microscopical examinations he observed laminated colloid, i.e. psammom bodies which contained calcium and iron, in the follicles of the thyroid glands of the old rats. Founding himself upon data of the literature, he deals with the questions of the occurrence and origin of the psammom bodies. Relying on his own examinations he is of the opinion that in the case of animals involution and dystrophic of a certain degree connected with senescence calls forth on oedema which and besides also the adenomas occurring in greater numbers means a disorder of the metabolic processes taking place in the thyroid gland and a possibility of the formation of psammom bodies. Eventually, in the authors opinion it cannot be stated with certainty -- at least in the case of animals -- that there is a close relationship between the occurrence of psammom bodies and the neoplasma."} {"id": "PMID:180709", "title": "[Enzyme histochemical studies on the macula and Goormaghtigh cells of the guinea pig kidney].", "content": "Starting from the ultrastructural differences observed between the juxtaglomerular apparatus of the rat and that--only very rarely analysed--of the guinea pig kidney, the authors supposed that enzymhistochemical differences might also exist. This hypothesis could be confirmed by the results obtained in the Macula densa- and the Goormaghtigh-cells (Tab. 1 and 2). Indeed, in both places the Isocitrate dehydrogenase- and the Malate dehydrogenase-activities are stronger in the guinea pig than in the rat. On the other hand, the Glucose-6-phosphate and the 6-Phosphogluconate dehydrogenases show clearly weaker activities in the guinea pig Macula-cells compared with those of the rat, where these two enzymes give by far the strongest reaction. Metabolic differences might be related to the described diversities of the enzyme equipment.", "contents": "[Enzyme histochemical studies on the macula and Goormaghtigh cells of the guinea pig kidney]. Starting from the ultrastructural differences observed between the juxtaglomerular apparatus of the rat and that--only very rarely analysed--of the guinea pig kidney, the authors supposed that enzymhistochemical differences might also exist. This hypothesis could be confirmed by the results obtained in the Macula densa- and the Goormaghtigh-cells (Tab. 1 and 2). Indeed, in both places the Isocitrate dehydrogenase- and the Malate dehydrogenase-activities are stronger in the guinea pig than in the rat. On the other hand, the Glucose-6-phosphate and the 6-Phosphogluconate dehydrogenases show clearly weaker activities in the guinea pig Macula-cells compared with those of the rat, where these two enzymes give by far the strongest reaction. Metabolic differences might be related to the described diversities of the enzyme equipment."} {"id": "PMID:180723", "title": "[The so-called amaurotic idiocies. Clinical, morphological and biochemical findings as a basis for modern classification].", "content": "First of all seven of our own thoroughly investigated cases of so-called amaurotic idiocies are presented, they are two infantile, two juvenile, two late infantile one, as well as one adult case. The two infantile cases represent the typ of a GM2-gangliosidosis: with cerebral symptoms and cherry-red spot in the macula they correspond clinically to the typical picture of Tay-Sachs disease. Lightmicroscopically they show neuronal storage, electronmicroscopically a deposition of \"membranous cytoplasmic bodies\" and biochemically a strong increase in ganglioside GM2. The two juvenile cases correspond in their symptoms and findings to the so-called ceroid-lipofuscinoses or \"Myoclonic variant of amaurotic idiocy\", respectively. Clinically most remarkable is the deterioration of vision caused by retinitis-pigmentosa-like changes of the fundus, which sets in at the beginning of the disease and precedes the cerebral symptoms by years. The extinguished electroretinogramm corresponds in the histological retina findings to a severe lesion of the layer of rods and cones in the sense of a tapeto-retinal degeneration. Neuropathologically finegranular, Sudan-Black-B- and PAS-positive material is mainly but not exclusively stored in the neurons. The electronmicroscope shows them to be lipofuscin-like inclusions, as well as \"curvilinear\" or \"fingerprint-bodies\". Depositions are also to be found in astrocytes and in the cells of the vascular walls. The ganglioside pattern is normal in the brain tissue of the biochemically investigated case. Of the two late infantile cases the first represents a GM2-gangliosidosis, the second one corresponds to the ceroid-lipofuscinosis. The adult patient, who suffered from an ill-defined psychiatric disease and died at the age of 51 presents a diagnostically problematic case, showing a relatively slight, regionally rather differently accentuated intraneuronal storage of granular material and biochemically a slight increase in ganglioside GM2. On discussing our own findings and commenting on the relevant literature various aspects of amaurotic idiocies are considered, such as genetics, neuropsychiatry, ophthalmology, pathomorphology and biochemistry. In this respect special attention is paid to the pathomorphological substrate documented, as localization, degree and kind of tissue changes determine the clinical picture. This is also the case for the correlation between the findings of the different fields, so e.g. concerning the ophthalmological findings it is shown, that in gangliosidoses with preserved ERG histologically a storage in the nerve cells of the ganglion cell-layer only is to be found, where as the ceroid-lipofuscinoses with early onset of deterioration of vision and extinguished ERG in the histological picture of the retina show an additional severe lesion of the layer of rods and cones...", "contents": "[The so-called amaurotic idiocies. Clinical, morphological and biochemical findings as a basis for modern classification]. First of all seven of our own thoroughly investigated cases of so-called amaurotic idiocies are presented, they are two infantile, two juvenile, two late infantile one, as well as one adult case. The two infantile cases represent the typ of a GM2-gangliosidosis: with cerebral symptoms and cherry-red spot in the macula they correspond clinically to the typical picture of Tay-Sachs disease. Lightmicroscopically they show neuronal storage, electronmicroscopically a deposition of \"membranous cytoplasmic bodies\" and biochemically a strong increase in ganglioside GM2. The two juvenile cases correspond in their symptoms and findings to the so-called ceroid-lipofuscinoses or \"Myoclonic variant of amaurotic idiocy\", respectively. Clinically most remarkable is the deterioration of vision caused by retinitis-pigmentosa-like changes of the fundus, which sets in at the beginning of the disease and precedes the cerebral symptoms by years. The extinguished electroretinogramm corresponds in the histological retina findings to a severe lesion of the layer of rods and cones in the sense of a tapeto-retinal degeneration. Neuropathologically finegranular, Sudan-Black-B- and PAS-positive material is mainly but not exclusively stored in the neurons. The electronmicroscope shows them to be lipofuscin-like inclusions, as well as \"curvilinear\" or \"fingerprint-bodies\". Depositions are also to be found in astrocytes and in the cells of the vascular walls. The ganglioside pattern is normal in the brain tissue of the biochemically investigated case. Of the two late infantile cases the first represents a GM2-gangliosidosis, the second one corresponds to the ceroid-lipofuscinosis. The adult patient, who suffered from an ill-defined psychiatric disease and died at the age of 51 presents a diagnostically problematic case, showing a relatively slight, regionally rather differently accentuated intraneuronal storage of granular material and biochemically a slight increase in ganglioside GM2. On discussing our own findings and commenting on the relevant literature various aspects of amaurotic idiocies are considered, such as genetics, neuropsychiatry, ophthalmology, pathomorphology and biochemistry. In this respect special attention is paid to the pathomorphological substrate documented, as localization, degree and kind of tissue changes determine the clinical picture. This is also the case for the correlation between the findings of the different fields, so e.g. concerning the ophthalmological findings it is shown, that in gangliosidoses with preserved ERG histologically a storage in the nerve cells of the ganglion cell-layer only is to be found, where as the ceroid-lipofuscinoses with early onset of deterioration of vision and extinguished ERG in the histological picture of the retina show an additional severe lesion of the layer of rods and cones..."} {"id": "PMID:180727", "title": "Poliovirus antibody differentiation. Methods and application for strain specific diagnosis in complications after oral vaccination.", "content": "Differentiation both of cf. and neutralizing antibodies against poliovirus seems to be a suitable method for the discrimination of the causative virus strain-either wild type or attenuated- of the clinical disease. Antibody differentiation is not only a completion of the virus strain differentiation methods (marker tests) but is especially of value in those cases in which no virus could be obtained for characterization, when indemnity claims for vaccination incidents are to be evaluated.", "contents": "Poliovirus antibody differentiation. Methods and application for strain specific diagnosis in complications after oral vaccination. Differentiation both of cf. and neutralizing antibodies against poliovirus seems to be a suitable method for the discrimination of the causative virus strain-either wild type or attenuated- of the clinical disease. Antibody differentiation is not only a completion of the virus strain differentiation methods (marker tests) but is especially of value in those cases in which no virus could be obtained for characterization, when indemnity claims for vaccination incidents are to be evaluated."} {"id": "PMID:180728", "title": "Varicella-zoster antibodies in adult patient with haemoblastoses.", "content": "Indirect haemagglutination (IH) antibodies to varicella-zoster (VZ) virus were investigated, under the identical conditions of a single experiment, in a group of patients with haemoblastoses and 80 normal adults of equal age groups. Statistical significance of the differences in VZ antibody geometric mean titres between the individual haemoblastoses and normal controls was examined by means of variance analysis. A significantly raised mean titre was still found in the Hodgkin's disease group.", "contents": "Varicella-zoster antibodies in adult patient with haemoblastoses. Indirect haemagglutination (IH) antibodies to varicella-zoster (VZ) virus were investigated, under the identical conditions of a single experiment, in a group of patients with haemoblastoses and 80 normal adults of equal age groups. Statistical significance of the differences in VZ antibody geometric mean titres between the individual haemoblastoses and normal controls was examined by means of variance analysis. A significantly raised mean titre was still found in the Hodgkin's disease group."} {"id": "PMID:180731", "title": "[Premature and usual periods of \"rapid\" sleep during attacks of diurnal narcolepsy].", "content": "The authors studied some psychophysiological characteristics of precocious and usual periods of rapid sleep in 17 patients with polysymptomatic narcolepsy during 92 attacks of day sleep. Precocious rapid sleep duffers from usual one in an inclusion into the dream content the experimental situations and their emotional saturation. The patients underestimated the duration of sleep and were unsatisfied by its quality. These differences indicate to a functional interconnection of rapid sleep with delta-sleep in the process of brain integration of information and assist to understand the pathogenesis of some traits of narcolepsy.", "contents": "[Premature and usual periods of \"rapid\" sleep during attacks of diurnal narcolepsy]. The authors studied some psychophysiological characteristics of precocious and usual periods of rapid sleep in 17 patients with polysymptomatic narcolepsy during 92 attacks of day sleep. Precocious rapid sleep duffers from usual one in an inclusion into the dream content the experimental situations and their emotional saturation. The patients underestimated the duration of sleep and were unsatisfied by its quality. These differences indicate to a functional interconnection of rapid sleep with delta-sleep in the process of brain integration of information and assist to understand the pathogenesis of some traits of narcolepsy."} {"id": "PMID:180734", "title": "On the occurrence of lipoprotein-x in non-hemolytic jaundice.", "content": "In cholestasis, serum lipids are altered. The alterations could at least partially be ascribed to the occurrence of an abnormal lipoprotein, LP-X. In 103 patients with jaundice, out of whom 16 had extra-hepatic cholestasis, the presence of LP-X was tested and semi-quantificated (by visual grading) utilizing an immunological technique. In extra-hepatic cholestasis, all patients showed LP-X in serum, while in intra-hepatic drug-induced cholestasis 87% revealed this phenomenon. At the initial stage of acute hepatitis, in drug-induced cholestasis, and in extra-hepatic cholestasis, the semi-quantificated LP-X correlated with alkaline phosphatase values. In extra-hepatic cholestasis, LP-X disappeared soon after the obstruction was relieved by operation.", "contents": "On the occurrence of lipoprotein-x in non-hemolytic jaundice. In cholestasis, serum lipids are altered. The alterations could at least partially be ascribed to the occurrence of an abnormal lipoprotein, LP-X. In 103 patients with jaundice, out of whom 16 had extra-hepatic cholestasis, the presence of LP-X was tested and semi-quantificated (by visual grading) utilizing an immunological technique. In extra-hepatic cholestasis, all patients showed LP-X in serum, while in intra-hepatic drug-induced cholestasis 87% revealed this phenomenon. At the initial stage of acute hepatitis, in drug-induced cholestasis, and in extra-hepatic cholestasis, the semi-quantificated LP-X correlated with alkaline phosphatase values. In extra-hepatic cholestasis, LP-X disappeared soon after the obstruction was relieved by operation."} {"id": "PMID:180739", "title": "The importance of growth hormone and liothyronine in induced hypocalcaemia in hypophysectomized animals.", "content": "The resistance to hypocalcaemia induced by synthetic salmon calcitonin (SCT) was studied in intact and hypophysectomized rats. The recovery from hypocalcaemia was greatly impaired in the latter group, but this was normalised by small doses of purified human growth hormone (GH). The initial hypocalcaemic response to SCT was delayed in the hypophysectomized rats. This was not affected by treatment with GH, but normalised by substitution with liothyronine. We conclude that GH accelerates the recovery from hypocalcaemia in hypophysectomized animals, perhaps by a stimulation of parathyroid activity, while thyroid hormone accelerates the initial hypocalcaemic response to SCT, probably by restoring the reduced rate of bone resorption.", "contents": "The importance of growth hormone and liothyronine in induced hypocalcaemia in hypophysectomized animals. The resistance to hypocalcaemia induced by synthetic salmon calcitonin (SCT) was studied in intact and hypophysectomized rats. The recovery from hypocalcaemia was greatly impaired in the latter group, but this was normalised by small doses of purified human growth hormone (GH). The initial hypocalcaemic response to SCT was delayed in the hypophysectomized rats. This was not affected by treatment with GH, but normalised by substitution with liothyronine. We conclude that GH accelerates the recovery from hypocalcaemia in hypophysectomized animals, perhaps by a stimulation of parathyroid activity, while thyroid hormone accelerates the initial hypocalcaemic response to SCT, probably by restoring the reduced rate of bone resorption."} {"id": "PMID:180738", "title": "Co-existent primary hypothyroidism and isolated ACTH deficiency.", "content": "A 52 year old man is described in whom the simultaneous occurrence of isolated adrenocorticotrophin (ACTH) deficiency and primary hypothyroidism was documented by the determination of six anterior pituitary hormones by specific radioimmunoassays after suitable stimulations. The urinary 17-hydroxycorticosteroids excretion was persistently reduced and was increased by repeated ACTH injections. The low basal metabolic rate, reduced serum thyroid hormones and elevated serum thyrotrophic hormone were consistent with primary hypothyroidism. After resumption of euthyroidism, secretory reserves of growth hormone and ACTH were assessed. The growth hormone reponse to insulin-induced hypoglycaemic was normal. No rise in plasma cortisol and ACTH was observed following insulin-induced hypoglycaemia. Plasma ACTH was not augmented by iv infusion of metyrapone. The pathogenesis of two co-existent endocrine deficiencies was discussed.", "contents": "Co-existent primary hypothyroidism and isolated ACTH deficiency. A 52 year old man is described in whom the simultaneous occurrence of isolated adrenocorticotrophin (ACTH) deficiency and primary hypothyroidism was documented by the determination of six anterior pituitary hormones by specific radioimmunoassays after suitable stimulations. The urinary 17-hydroxycorticosteroids excretion was persistently reduced and was increased by repeated ACTH injections. The low basal metabolic rate, reduced serum thyroid hormones and elevated serum thyrotrophic hormone were consistent with primary hypothyroidism. After resumption of euthyroidism, secretory reserves of growth hormone and ACTH were assessed. The growth hormone reponse to insulin-induced hypoglycaemic was normal. No rise in plasma cortisol and ACTH was observed following insulin-induced hypoglycaemia. Plasma ACTH was not augmented by iv infusion of metyrapone. The pathogenesis of two co-existent endocrine deficiencies was discussed."} {"id": "PMID:180740", "title": "In vitro synthesis of steroids by a feminising adrenocortical carcinoma: effect of prolactin and other protein hormones.", "content": "The study describes the effects of ACTH, prolactin and other protein hormones on the synthesis and secretion of steroid hormones by tissue from a feminising adrenocortical carcinoma removed from a post-menopausal female. Steroid production by the tissue was determined by high resolution-mass fragmentography and by radioimmunoassay. Prolactin and ACTH stimulated the synthesis of estrogens by the tissue whereas GH, LH and ACTH were more effective than prolactin in stimulating androgen synthesis. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumour tissue indicated a lack of specificity of the membrane receptor sites.", "contents": "In vitro synthesis of steroids by a feminising adrenocortical carcinoma: effect of prolactin and other protein hormones. The study describes the effects of ACTH, prolactin and other protein hormones on the synthesis and secretion of steroid hormones by tissue from a feminising adrenocortical carcinoma removed from a post-menopausal female. Steroid production by the tissue was determined by high resolution-mass fragmentography and by radioimmunoassay. Prolactin and ACTH stimulated the synthesis of estrogens by the tissue whereas GH, LH and ACTH were more effective than prolactin in stimulating androgen synthesis. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumour tissue indicated a lack of specificity of the membrane receptor sites."} {"id": "PMID:180736", "title": "Seminal vesicle epithelium in fine-needle aspiration biopsies of the prostate as a pitfall in the cytologic diagnosis of carcinoma.", "content": "The morphologic features of seminal vesicle epithelial cells were studied in a material of ca 3,300 fine-needle aspiration biopsies of the prostate. Seminal vesicle material was considered to be found in 50 cases. The most usual and distinctive features in seminal vesicle epithelial cells were yellowish-brown cytoplasmic pigment granules and large hyperchromatic polyploid nuclei. Intranuclear cytoplasmic inclusions, nuclear folding and prominent nucleoli were observed in approximately one third of the cases. Seminal vesicle secretion and stromal cells were seen in most cases, spermatozoa less frequently. The recognition of seminal vesicle epithelial cells in fine-needle aspiration biopsies of the prostate is considered to be important in the avoidance of cytodiagnostic errors.", "contents": "Seminal vesicle epithelium in fine-needle aspiration biopsies of the prostate as a pitfall in the cytologic diagnosis of carcinoma. The morphologic features of seminal vesicle epithelial cells were studied in a material of ca 3,300 fine-needle aspiration biopsies of the prostate. Seminal vesicle material was considered to be found in 50 cases. The most usual and distinctive features in seminal vesicle epithelial cells were yellowish-brown cytoplasmic pigment granules and large hyperchromatic polyploid nuclei. Intranuclear cytoplasmic inclusions, nuclear folding and prominent nucleoli were observed in approximately one third of the cases. Seminal vesicle secretion and stromal cells were seen in most cases, spermatozoa less frequently. The recognition of seminal vesicle epithelial cells in fine-needle aspiration biopsies of the prostate is considered to be important in the avoidance of cytodiagnostic errors."} {"id": "PMID:180741", "title": "Plasma aldosterone concentrations related to 17alpha-hydroxyprogesterone in congenital adrenal hyperplasia.", "content": "Plasma aldosterone and 17alpha-hydroxyprogesterone (17-OHP) concentrations were measured in 35 patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. Ten patients had never been treated and among them were 4 salt-losing infants. Both aldosterone and 17-OHP were high in the 6 untreated non salt-losers. The values ranged respectively from 110 to 376 pg/ml and from 150 to 292 ng/ml. Results were variable in the 4 salt-losers. Three out of 5 untreated non salt-losers who were submitted to a low sodium diet, responded by doubling their aldosterone levels. When plasma 17-OHP concentrations were less than 30 ng/ml, the mean aldosterone level in the treated non salt-losers (n=6) was 15.3 pg/ml +/- 4.3 (SE). This value was not different from the mean level found in the control children (n=7), 18.8 pg/ml +/- 3.2. In the treated salt-losers (n=9), the measured aldosterone levels were less than or equal to 10 pg/ml 7 times out of 9. When the treated patients exhibited plasma 17-OHP concentrations greater than 30 ng/ml, the salt-losers (n=11) were distinguished from the non salt-losers (n=8) in that they showed as significantly lower aldosterone mean level, 24.6 pg/ml +/- 4.3 against 69 pg/ml +/- 13.4 found in the non salt-losers. The salt-losers displayed no aldosterone increases to synthetic ACTH stimulation under treatment or at the withdrawal of treatment, while positive aldosterone responses were often observed in the non salt-losers. In the latter group, studied under different conditions (with and without therapy, on low sodium diet, after ACTH test) a significant correlation was found between aldosterone and 17-OHP levels expressed in log. values, (n=38, r=0.80, P less than 0.001). The relationship could also be established with the values obtained from all the salt-losers, but it was less significant, (n=35, r=0.46, P less than 0.02).", "contents": "Plasma aldosterone concentrations related to 17alpha-hydroxyprogesterone in congenital adrenal hyperplasia. Plasma aldosterone and 17alpha-hydroxyprogesterone (17-OHP) concentrations were measured in 35 patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. Ten patients had never been treated and among them were 4 salt-losing infants. Both aldosterone and 17-OHP were high in the 6 untreated non salt-losers. The values ranged respectively from 110 to 376 pg/ml and from 150 to 292 ng/ml. Results were variable in the 4 salt-losers. Three out of 5 untreated non salt-losers who were submitted to a low sodium diet, responded by doubling their aldosterone levels. When plasma 17-OHP concentrations were less than 30 ng/ml, the mean aldosterone level in the treated non salt-losers (n=6) was 15.3 pg/ml +/- 4.3 (SE). This value was not different from the mean level found in the control children (n=7), 18.8 pg/ml +/- 3.2. In the treated salt-losers (n=9), the measured aldosterone levels were less than or equal to 10 pg/ml 7 times out of 9. When the treated patients exhibited plasma 17-OHP concentrations greater than 30 ng/ml, the salt-losers (n=11) were distinguished from the non salt-losers (n=8) in that they showed as significantly lower aldosterone mean level, 24.6 pg/ml +/- 4.3 against 69 pg/ml +/- 13.4 found in the non salt-losers. The salt-losers displayed no aldosterone increases to synthetic ACTH stimulation under treatment or at the withdrawal of treatment, while positive aldosterone responses were often observed in the non salt-losers. In the latter group, studied under different conditions (with and without therapy, on low sodium diet, after ACTH test) a significant correlation was found between aldosterone and 17-OHP levels expressed in log. values, (n=38, r=0.80, P less than 0.001). The relationship could also be established with the values obtained from all the salt-losers, but it was less significant, (n=35, r=0.46, P less than 0.02)."} {"id": "PMID:180737", "title": "Cytologic characteristics of adenoid cystic carcinoma of the cervix uteri.", "content": "Cytologic characteristics of three cases of adenoid cystic carcinoma of the cervix uteri are reviewed. The clusters of malignant cells tend to form large acini and mimic the pattern seen in histologic sections. The resemblance to cells of adenocarcinoma of the endometrium is noted. When the acinar pattern is recognized in cervical smears, adenoid cystic carcinoma of the cervix may be suspected.", "contents": "Cytologic characteristics of adenoid cystic carcinoma of the cervix uteri. Cytologic characteristics of three cases of adenoid cystic carcinoma of the cervix uteri are reviewed. The clusters of malignant cells tend to form large acini and mimic the pattern seen in histologic sections. The resemblance to cells of adenocarcinoma of the endometrium is noted. When the acinar pattern is recognized in cervical smears, adenoid cystic carcinoma of the cervix may be suspected."} {"id": "PMID:180742", "title": "Effects of ACTH and its O-nitrophenyl sulphenyl derivative on adrenocortical function in vivo.", "content": "Both ACTH and NPS-ACTH in which the single tryptophan residue of the hormone is modified were able to stimulate adrenal corticosterone concentration to the same extent in hypophysectomized rats, although a higher dose of NPS-ACTH was required. ACTH stimulated adrenal cyclic AMP levels 120-fold in hypophysectomized rats whereas NPS-ACTH caused a marginal increase. In the case of ACTH, low doses of the hormone capable of producing maximal stimulation of corticosterone synthesis did not produce any detectable change in cyclic AMP concentration. The rates of secretion of corticosterone induced by ACTH and NPS-ACTH in vivo were the same. NPS-ACTH was found to be 1.2% as potent as ACTH. The role of cyclic AMP in adrenal repair was investigated by administering equipotent doses of ACTH or NPS-ACTH to hypophysectomized rats. In adult rats both failed to produce a significant increase in adrenal weight. Adrenal function (measured by responsiveness to exogenous ACTH in vitro) was restored by NPS-ACTH but not to the same degree as ACTH. In hypophysectomized weanling rats, ACTH produced a small but significant increase in adrenal weight but NPS-ACTH did not. These results suggest that an increase in adrenal cyclic AMP may not be obligatory for the stimulation of steroidogenesis by ACTH and that some of the trophic actions of the hormone may be mediated by cyclic AMP.", "contents": "Effects of ACTH and its O-nitrophenyl sulphenyl derivative on adrenocortical function in vivo. Both ACTH and NPS-ACTH in which the single tryptophan residue of the hormone is modified were able to stimulate adrenal corticosterone concentration to the same extent in hypophysectomized rats, although a higher dose of NPS-ACTH was required. ACTH stimulated adrenal cyclic AMP levels 120-fold in hypophysectomized rats whereas NPS-ACTH caused a marginal increase. In the case of ACTH, low doses of the hormone capable of producing maximal stimulation of corticosterone synthesis did not produce any detectable change in cyclic AMP concentration. The rates of secretion of corticosterone induced by ACTH and NPS-ACTH in vivo were the same. NPS-ACTH was found to be 1.2% as potent as ACTH. The role of cyclic AMP in adrenal repair was investigated by administering equipotent doses of ACTH or NPS-ACTH to hypophysectomized rats. In adult rats both failed to produce a significant increase in adrenal weight. Adrenal function (measured by responsiveness to exogenous ACTH in vitro) was restored by NPS-ACTH but not to the same degree as ACTH. In hypophysectomized weanling rats, ACTH produced a small but significant increase in adrenal weight but NPS-ACTH did not. These results suggest that an increase in adrenal cyclic AMP may not be obligatory for the stimulation of steroidogenesis by ACTH and that some of the trophic actions of the hormone may be mediated by cyclic AMP."} {"id": "PMID:180743", "title": "Ultrastructure of the Gunn rat substantia nigra I. Cytoplasmic changes.", "content": "The substantia nigra of various aged hyperbilirubinemic (Gunn) rats was studied by means of electron microscopy. The cytological features observed in the neuronal somata were the presence of (1) complex membranous bodies (CMBs), (2) dilated cisternae of granular endoplasmic reticulum, (3) single membrane bound vacuoles and (4) enlarged mitochondria. Nearly every neuronal soma studied in two week old Gunn rats contained CMBs, which consisted of several layers of membrane that usually, but not always surrounded small islands of cytoplasm. On occasion CMBs were seen to be directly connected with granular endoplasmic reticulum and, in a few instances, they were located within a cistern of endoplasmic reticulum. There were significantly fewer CMBs in the neuronal somata of adult Gunn rats. They were located peripherally in the somata or in the proximal portions of dendrites. Furthermore, in these animals the cytoplasm appeared normal and did not exhibit the features commonly seen in younger animals. Only a few hyperchromatic neurons were observed and no pronounced gliosis was evident. Therefore it is assumed that the majority of substantia nigra neurons recovered from the toxic effect of bilirubin or that the concentration of bilirubin deposited in the substantia nigra is not sufficient to be lethal. The hypothesis that is considered is that CMBs represent autophagic activity which results from exposure of neurons to bilirubin. The adjacent neurites and glia did not demonstrate the cytoplasmic changes that were characteristic of the neuronal somata.", "contents": "Ultrastructure of the Gunn rat substantia nigra I. Cytoplasmic changes. The substantia nigra of various aged hyperbilirubinemic (Gunn) rats was studied by means of electron microscopy. The cytological features observed in the neuronal somata were the presence of (1) complex membranous bodies (CMBs), (2) dilated cisternae of granular endoplasmic reticulum, (3) single membrane bound vacuoles and (4) enlarged mitochondria. Nearly every neuronal soma studied in two week old Gunn rats contained CMBs, which consisted of several layers of membrane that usually, but not always surrounded small islands of cytoplasm. On occasion CMBs were seen to be directly connected with granular endoplasmic reticulum and, in a few instances, they were located within a cistern of endoplasmic reticulum. There were significantly fewer CMBs in the neuronal somata of adult Gunn rats. They were located peripherally in the somata or in the proximal portions of dendrites. Furthermore, in these animals the cytoplasm appeared normal and did not exhibit the features commonly seen in younger animals. Only a few hyperchromatic neurons were observed and no pronounced gliosis was evident. Therefore it is assumed that the majority of substantia nigra neurons recovered from the toxic effect of bilirubin or that the concentration of bilirubin deposited in the substantia nigra is not sufficient to be lethal. The hypothesis that is considered is that CMBs represent autophagic activity which results from exposure of neurons to bilirubin. The adjacent neurites and glia did not demonstrate the cytoplasmic changes that were characteristic of the neuronal somata."} {"id": "PMID:180745", "title": "The efficacy of melphalan in the combined chemotherapy of malignant trophoblastic disease.", "content": "Steadily progressive improvement in the diagnostic and therapeutic management of malignant trophoblastic disease has occurred over the last few decades. The most important diagnostic aid is the determination of serum HCG by sensitive radioimmunoassay which allows the detection of minute amounts of the hormone and permits discrimination between LH and HCG. Therapeutic advances include the use of combinations of different cytostatic drugs which have increased the cure rate from approximately 50% to a range of 80-95% (1, 2, 3, 4, 5, 6, 7). Malignant trophoblastic disease is rare in the Scandinavian countries which effectively limits opportunities to acquire experience within individual centers. However, a series of 23 cases has been collected at the Karolinska Hospital during the last 10 years. Patients who developed resistance against methotrexate were successfully treated by a combination of an alkylating agent melphalan (Alkeran), actinomycin D and methotrexate. In some cases this modification of a triple-therapy regimen has turned out to be life-saving.", "contents": "The efficacy of melphalan in the combined chemotherapy of malignant trophoblastic disease. Steadily progressive improvement in the diagnostic and therapeutic management of malignant trophoblastic disease has occurred over the last few decades. The most important diagnostic aid is the determination of serum HCG by sensitive radioimmunoassay which allows the detection of minute amounts of the hormone and permits discrimination between LH and HCG. Therapeutic advances include the use of combinations of different cytostatic drugs which have increased the cure rate from approximately 50% to a range of 80-95% (1, 2, 3, 4, 5, 6, 7). Malignant trophoblastic disease is rare in the Scandinavian countries which effectively limits opportunities to acquire experience within individual centers. However, a series of 23 cases has been collected at the Karolinska Hospital during the last 10 years. Patients who developed resistance against methotrexate were successfully treated by a combination of an alkylating agent melphalan (Alkeran), actinomycin D and methotrexate. In some cases this modification of a triple-therapy regimen has turned out to be life-saving."} {"id": "PMID:180749", "title": "Adrenocorticotrophin and glucocorticoid response to exchange transfusion.", "content": "Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusion with ACD blood via the umbilical artery were performed on 10 infants of 35--40 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled and then doubled in the second and third hour. The results suggest that (a) exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, (b) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature ifants, (c) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2-3 hours after all types of transfusion.", "contents": "Adrenocorticotrophin and glucocorticoid response to exchange transfusion. Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusion with ACD blood via the umbilical artery were performed on 10 infants of 35--40 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled and then doubled in the second and third hour. The results suggest that (a) exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, (b) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature ifants, (c) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2-3 hours after all types of transfusion."} {"id": "PMID:180750", "title": "Pseudohypoparathyroidism: a difficult diagnosis in early childhood.", "content": "We have studied one adult and three children with pseudohypoparathyroidism and observed that the physical character of short metacarpal bones is not evident in the first 4-5 years of life, that hypocalcaemia and hyperphosphataemia may be absent in the first years of life, but that the renal unresponsiveness to parathyroid hormone can still be demonstrated. Our data confirm earlier observation that in evaluating the renal responsiveness to parathyroid hormone, urinary cyclic AMP is a better parameter than urinary phosphorus. Thus in early childhood, it may be difficult to differentiate between a normal child, a child with pseudohypoparathyroidism and a child with pseudo-pseudohypoparathyroidism unless the renal parathyroid hormone responsiveness is studied.", "contents": "Pseudohypoparathyroidism: a difficult diagnosis in early childhood. We have studied one adult and three children with pseudohypoparathyroidism and observed that the physical character of short metacarpal bones is not evident in the first 4-5 years of life, that hypocalcaemia and hyperphosphataemia may be absent in the first years of life, but that the renal unresponsiveness to parathyroid hormone can still be demonstrated. Our data confirm earlier observation that in evaluating the renal responsiveness to parathyroid hormone, urinary cyclic AMP is a better parameter than urinary phosphorus. Thus in early childhood, it may be difficult to differentiate between a normal child, a child with pseudohypoparathyroidism and a child with pseudo-pseudohypoparathyroidism unless the renal parathyroid hormone responsiveness is studied."} {"id": "PMID:180754", "title": "A comparative study of DNA-dependent RNA polymerases from rat ascites hepatoma cell nuclei and from rat liver nuclei.", "content": "DNA-dependent RNA polymerases (EC 2.7.7.6) were extracted and partially purified form the nuclei of rat ascites hepatoma cells (AH-130) induced by 4-dimethylaminoazobenzene. The patterns of RNA synthesis and the properties of these enzymes were compared with enzymes from the nuclei of rat liver. The specific activity of RNA polymerase in the homogenate from the nuclei of AH-130 cells was the same as normal rat liver nuclei. RNA polymerase was solubilized from the homogenate at high ionic strength and separated into two forms by DEAE-Sephadex column chromatography. Enzymatic characterization showed that these enzymes corresponded to RNA polymerase I and II. RNA polymerase I more effectively transcribed native DNA than denatured DNA at low salt concentration, but at high salt concentration RNA polymerase I effectively transcribed denatured DNA. RNA polymerase II more effectively transcribed denatured DNA. In AH-130 cells the activity of RNA polymerase I was 4 to 5 times higher than RNA polymerase II, and in rat liver the activity of RNA polymerase I was 1.5 to 2 times higher than RNA polymerase II. The activity of RNA polymerase I in AH-130 cells may have increased by induction.", "contents": "A comparative study of DNA-dependent RNA polymerases from rat ascites hepatoma cell nuclei and from rat liver nuclei. DNA-dependent RNA polymerases (EC 2.7.7.6) were extracted and partially purified form the nuclei of rat ascites hepatoma cells (AH-130) induced by 4-dimethylaminoazobenzene. The patterns of RNA synthesis and the properties of these enzymes were compared with enzymes from the nuclei of rat liver. The specific activity of RNA polymerase in the homogenate from the nuclei of AH-130 cells was the same as normal rat liver nuclei. RNA polymerase was solubilized from the homogenate at high ionic strength and separated into two forms by DEAE-Sephadex column chromatography. Enzymatic characterization showed that these enzymes corresponded to RNA polymerase I and II. RNA polymerase I more effectively transcribed native DNA than denatured DNA at low salt concentration, but at high salt concentration RNA polymerase I effectively transcribed denatured DNA. RNA polymerase II more effectively transcribed denatured DNA. In AH-130 cells the activity of RNA polymerase I was 4 to 5 times higher than RNA polymerase II, and in rat liver the activity of RNA polymerase I was 1.5 to 2 times higher than RNA polymerase II. The activity of RNA polymerase I in AH-130 cells may have increased by induction."} {"id": "PMID:180755", "title": "A new histochemical method using human placenta alkaline phosphatase for demonstrating concanavalin A binding sites on cell surfaces.", "content": "Human placenta alkaline phosphatase (HP-ALP), a glycoprotein, was stained histochemically for the purpose of examining the concanavalin A (Con A) binding sites on the cell surface. HP-ALP was bound to the cell surface by Con A. This simple method successfully detected Con A binding sites on the cell surface.", "contents": "A new histochemical method using human placenta alkaline phosphatase for demonstrating concanavalin A binding sites on cell surfaces. Human placenta alkaline phosphatase (HP-ALP), a glycoprotein, was stained histochemically for the purpose of examining the concanavalin A (Con A) binding sites on the cell surface. HP-ALP was bound to the cell surface by Con A. This simple method successfully detected Con A binding sites on the cell surface."} {"id": "PMID:180756", "title": "Interferon production by human leukaemic leucocytes.", "content": "The Sendai virus-induced interferon (IF) production by partially purified human leucocyte suspensions of normal donors and of leukaemic patients have been investigated in vitro. (i) An increased production was observed with leucocytes taken from patients suffering from chronic myelogenous leukaemia (CML) during exacerbation, but the production was approximately normal with cells taken during remission. (ii) IF production was not influenced by large doses of cytostatics (DBM, 5-FU, FUDR, 5-HU, 6-MP, cyclophosphamide) irrespective of whether normal or CML leucocytes were used. (iii) In contrast, production was inhibited in both systems by inhibitors of RNA or protein synthesis (actinomycin D, puromycin, cycloheximide). (iv) CML leucocytes produced IF for a prolonged period of time as compared to normal leucocytes. (v) Leucocytes from children with acute blastic leukaemia and those from adults with chronic lymphoid or acute paramyeloblastic leukaemia produce, in contrast to normal leukocytes, approximately as much IF in the absence as in the presence of serum. It is concluded that the Sendai virus-induced IF synthesis in CML leucocytes requires de novo protein synthesis.", "contents": "Interferon production by human leukaemic leucocytes. The Sendai virus-induced interferon (IF) production by partially purified human leucocyte suspensions of normal donors and of leukaemic patients have been investigated in vitro. (i) An increased production was observed with leucocytes taken from patients suffering from chronic myelogenous leukaemia (CML) during exacerbation, but the production was approximately normal with cells taken during remission. (ii) IF production was not influenced by large doses of cytostatics (DBM, 5-FU, FUDR, 5-HU, 6-MP, cyclophosphamide) irrespective of whether normal or CML leucocytes were used. (iii) In contrast, production was inhibited in both systems by inhibitors of RNA or protein synthesis (actinomycin D, puromycin, cycloheximide). (iv) CML leucocytes produced IF for a prolonged period of time as compared to normal leucocytes. (v) Leucocytes from children with acute blastic leukaemia and those from adults with chronic lymphoid or acute paramyeloblastic leukaemia produce, in contrast to normal leukocytes, approximately as much IF in the absence as in the presence of serum. It is concluded that the Sendai virus-induced IF synthesis in CML leucocytes requires de novo protein synthesis."} {"id": "PMID:180757", "title": "Serological differential diagnosis of viral hepatitis in adults.", "content": "Serum samples from different groups of adults were tested for HBsAg and IHxAg, using a complement-fixation microtest and the Indian-ink immune reaction, respectively. (i) In healthy men 18-24 years of age, living in camps in closed communities, HBsAg was demonstrated in 1.5%, IHxAg in 12.2%, and both antigens in 0.7%. The incidence of HBsAg positivity seems to be age-dependent and influenced by environmental factors. (ii) For patients hospitalized with liver and/or biliary-tract diseases other than hepatitis, the respective percentages were 10, 13.5 and 4.5%. (iii) Of the cases clinically diagnosed as infectious hepatitis (IH, hepatitis A) or serum hepatitis (SH, hepatitis B), 14% were positive for both antigens whereas 10% were double-negative; 76% were positive for either HBsAg or IHxAg. In two-thirds of the single-positive cases the demonstrated antigen agreed with the clinical diagnosis, in one-third the unexpected antigen was present. (iv) SGPT and thymol turbidity values agreed better with the serological findings that with the clinical diagnosis. The number of days in hospital appeared to be related to both the serological findings and the clinical diagnosis. The clinical course was the most severe for those having both antigens in blood. (v) IHxantibodies from early convalescence were sensitive, those from a later stage were resistant, to 2-mercaptoethanol. (vi) No correlation was found between the presence of IHxAg and that of the rheumatoid factor. (vii) The IHx Indian-ink reaction is disturbed by the presence of labile serum proteins while the essentially similar reverse passive haemagglutination reaction was not affected by them. (viii) Testing for IHxAg seems to be a procedure valuable in the differential diagnosis of IH and SH, though the results are less convincing in adult age than in childhood.", "contents": "Serological differential diagnosis of viral hepatitis in adults. Serum samples from different groups of adults were tested for HBsAg and IHxAg, using a complement-fixation microtest and the Indian-ink immune reaction, respectively. (i) In healthy men 18-24 years of age, living in camps in closed communities, HBsAg was demonstrated in 1.5%, IHxAg in 12.2%, and both antigens in 0.7%. The incidence of HBsAg positivity seems to be age-dependent and influenced by environmental factors. (ii) For patients hospitalized with liver and/or biliary-tract diseases other than hepatitis, the respective percentages were 10, 13.5 and 4.5%. (iii) Of the cases clinically diagnosed as infectious hepatitis (IH, hepatitis A) or serum hepatitis (SH, hepatitis B), 14% were positive for both antigens whereas 10% were double-negative; 76% were positive for either HBsAg or IHxAg. In two-thirds of the single-positive cases the demonstrated antigen agreed with the clinical diagnosis, in one-third the unexpected antigen was present. (iv) SGPT and thymol turbidity values agreed better with the serological findings that with the clinical diagnosis. The number of days in hospital appeared to be related to both the serological findings and the clinical diagnosis. The clinical course was the most severe for those having both antigens in blood. (v) IHxantibodies from early convalescence were sensitive, those from a later stage were resistant, to 2-mercaptoethanol. (vi) No correlation was found between the presence of IHxAg and that of the rheumatoid factor. (vii) The IHx Indian-ink reaction is disturbed by the presence of labile serum proteins while the essentially similar reverse passive haemagglutination reaction was not affected by them. (viii) Testing for IHxAg seems to be a procedure valuable in the differential diagnosis of IH and SH, though the results are less convincing in adult age than in childhood."} {"id": "PMID:180758", "title": "Virus content and effectiveness of foot-and-mouth disease vaccines.", "content": "(I) The amount of 22 nm particles in 26 batches of cattle tongue epithelium extract used for the preparation of C-type vaccine was determined with an improved 50% haemolytic and point complement fixation test after fluorocarbon precipitation of non-immunizing 7 nm particles. The total amount of 22 nm and 7 nm particles (alpha GN value) varied considerably from batch to batch, 22 nm components (alpha GF value) showing a maximum 5-fold difference. (ii) Effectiveness of vaccines with known virus content was tested in adult mice challenged with an adapted virus strain. In commercial C-type vaccines the complement-fixing activitiy of 22 nm particles and the potency of the vaccine showed a logarithmic regression (mouse index = -1.43 + 2.27 1g alpha GF).", "contents": "Virus content and effectiveness of foot-and-mouth disease vaccines. (I) The amount of 22 nm particles in 26 batches of cattle tongue epithelium extract used for the preparation of C-type vaccine was determined with an improved 50% haemolytic and point complement fixation test after fluorocarbon precipitation of non-immunizing 7 nm particles. The total amount of 22 nm and 7 nm particles (alpha GN value) varied considerably from batch to batch, 22 nm components (alpha GF value) showing a maximum 5-fold difference. (ii) Effectiveness of vaccines with known virus content was tested in adult mice challenged with an adapted virus strain. In commercial C-type vaccines the complement-fixing activitiy of 22 nm particles and the potency of the vaccine showed a logarithmic regression (mouse index = -1.43 + 2.27 1g alpha GF)."} {"id": "PMID:180760", "title": "Effect of rehydration of rat liver tissue after water deprivation.", "content": "Male albino rats were deprived of water for 6 days, then they were allowed to drink tap water ad libitim. The structure of the liver was examined by light and electron microscopy, and the protein and dry matter contents, oxygen consumption and glucose-6-phosphatase activity of the liver were determined after rehydration. At 10 minutes, the mitochondria showed signs of division and a peculiar transformation of the cristae. At 60 minutes, the membranes of the rough endoplasmic reticulum were found to have proliferated. At 12 hours, the smooth-surfaced membranes showed hypertrophy and the bile canaliculi were distended. At 24 hours all rehydration induced organelle alterations were declining. The biochemical findings agreed well with the fine structural changes and both were indicative of an enchanced functional capacity of liver cells during rehydration.", "contents": "Effect of rehydration of rat liver tissue after water deprivation. Male albino rats were deprived of water for 6 days, then they were allowed to drink tap water ad libitim. The structure of the liver was examined by light and electron microscopy, and the protein and dry matter contents, oxygen consumption and glucose-6-phosphatase activity of the liver were determined after rehydration. At 10 minutes, the mitochondria showed signs of division and a peculiar transformation of the cristae. At 60 minutes, the membranes of the rough endoplasmic reticulum were found to have proliferated. At 12 hours, the smooth-surfaced membranes showed hypertrophy and the bile canaliculi were distended. At 24 hours all rehydration induced organelle alterations were declining. The biochemical findings agreed well with the fine structural changes and both were indicative of an enchanced functional capacity of liver cells during rehydration."} {"id": "PMID:180761", "title": "Intranuclear virus-like particles in HBsAG- and IHxAG-negative acute hepatitis (type C?) (Preliminary report).", "content": "Virus-like particles, acute hepatitis, hepatitis type C. Intranuclear virus-like particles were found by electron microscopy in liver cells of a woman suffering from mild HBsAG- and IHxAG negative acute hepatitis. The particles encountered were morphologically different from those found in hepatitis B and hepatitis A respectively. Futher studies are required to clarify whether the structures represent an incidental finding of a new human (passenger) virus or they may be related to the aetiological agent of the supposed hepatitis type C.", "contents": "Intranuclear virus-like particles in HBsAG- and IHxAG-negative acute hepatitis (type C?) (Preliminary report). Virus-like particles, acute hepatitis, hepatitis type C. Intranuclear virus-like particles were found by electron microscopy in liver cells of a woman suffering from mild HBsAG- and IHxAG negative acute hepatitis. The particles encountered were morphologically different from those found in hepatitis B and hepatitis A respectively. Futher studies are required to clarify whether the structures represent an incidental finding of a new human (passenger) virus or they may be related to the aetiological agent of the supposed hepatitis type C."} {"id": "PMID:180770", "title": "Biochemical evidence on the role of gangliosides in nerve-endings.", "content": "From the biochemical and developmental data in the literature, there appears to be some specific relationship of gangliosides to synapses. Whether the concentration of polysialo-gangliosides is located in the immediately pre-synaptic part of the neuronal plasma membrane is not known. There are many unanswered questions about the gangliosides, which we have attempted to pose in this article. There are as many hypotheses about roles for gangliosides, and virtually no data to back them up. In fact there are not even real indications of possible functions. We believe that it will be very difficult to define the functions of gangliosides until more of the basic questions are answered-even if their synaptic localization is a constant temptation to speculate.", "contents": "Biochemical evidence on the role of gangliosides in nerve-endings. From the biochemical and developmental data in the literature, there appears to be some specific relationship of gangliosides to synapses. Whether the concentration of polysialo-gangliosides is located in the immediately pre-synaptic part of the neuronal plasma membrane is not known. There are many unanswered questions about the gangliosides, which we have attempted to pose in this article. There are as many hypotheses about roles for gangliosides, and virtually no data to back them up. In fact there are not even real indications of possible functions. We believe that it will be very difficult to define the functions of gangliosides until more of the basic questions are answered-even if their synaptic localization is a constant temptation to speculate."} {"id": "PMID:180771", "title": "Possible functional role of gangliosides.", "content": "The brain ganglioside pattern of taxonomically close and distant related fish living at different temperatures were compared with the mammalian pattern. Furthermore the goldfish brain pattern was investigated after adaption (acclimitization, acclimation) to different temperatures. The results demonstrate correlations between body temperature and brain gangliosides: the lower the body temperature of animals, the higher the relative proportion of multi-sialo-gangliosides. The results are discussed with respect to the possible functional role of Ca++-ganglioside-complexes for the process of synaptic transmission.", "contents": "Possible functional role of gangliosides. The brain ganglioside pattern of taxonomically close and distant related fish living at different temperatures were compared with the mammalian pattern. Furthermore the goldfish brain pattern was investigated after adaption (acclimitization, acclimation) to different temperatures. The results demonstrate correlations between body temperature and brain gangliosides: the lower the body temperature of animals, the higher the relative proportion of multi-sialo-gangliosides. The results are discussed with respect to the possible functional role of Ca++-ganglioside-complexes for the process of synaptic transmission."} {"id": "PMID:180773", "title": "Effects of brain gangliosides on functional recovery in experimental regeneration and reinnervation.", "content": "The effect of brain cortex gangliosides has been tested in two different experimental models of peripheral sympathetic regeneration and reinnervation: a) the preganglionic trunks of the cervical sympathetic nerve were joined in an end-to-end anastomosis after severing the preganglionic trunk, caudally to the superior cervical ganglion; this reinnervation is mainly of cholinergic type. b) the postganglionic trunks of the superior cervical ganglion were joined in an end-to-end anastomosis after severing the postganglionic trunk; this reinnervation is mainly of adrenergic type. Functional recovery following the regeneration and reinnervation has been evaluated by measuring tha contraction of the nictitating membrane, evoked by electrical stimulation of the sympathetic trunk caudally to the point of anastomosis. Some of the operated animals were daily treated with 50mg/kg i.p. of brain cortex gangliosides during the entire post-operative period. Forty-five, sixty days after the operation we observed in the treated animals of both experimental sets a relevant increase in the functional recovery (between 30 and 100%) compared to the operated but untreated controls. In the case of postganglionic anastomosis the physio-pharmacological studies were substantiated by the histochemical fluorescence observations of the distributions of catecholamines in the smooth muscle of the nictitating membranes. These results strongly suggest that the treatment with gangliosides greatly influences the regeneration and reinnervation process of both cholinergic and adrenergic nerve fibers.", "contents": "Effects of brain gangliosides on functional recovery in experimental regeneration and reinnervation. The effect of brain cortex gangliosides has been tested in two different experimental models of peripheral sympathetic regeneration and reinnervation: a) the preganglionic trunks of the cervical sympathetic nerve were joined in an end-to-end anastomosis after severing the preganglionic trunk, caudally to the superior cervical ganglion; this reinnervation is mainly of cholinergic type. b) the postganglionic trunks of the superior cervical ganglion were joined in an end-to-end anastomosis after severing the postganglionic trunk; this reinnervation is mainly of adrenergic type. Functional recovery following the regeneration and reinnervation has been evaluated by measuring tha contraction of the nictitating membrane, evoked by electrical stimulation of the sympathetic trunk caudally to the point of anastomosis. Some of the operated animals were daily treated with 50mg/kg i.p. of brain cortex gangliosides during the entire post-operative period. Forty-five, sixty days after the operation we observed in the treated animals of both experimental sets a relevant increase in the functional recovery (between 30 and 100%) compared to the operated but untreated controls. In the case of postganglionic anastomosis the physio-pharmacological studies were substantiated by the histochemical fluorescence observations of the distributions of catecholamines in the smooth muscle of the nictitating membranes. These results strongly suggest that the treatment with gangliosides greatly influences the regeneration and reinnervation process of both cholinergic and adrenergic nerve fibers."} {"id": "PMID:180775", "title": "Remote effects of focal cancer on the neuromuscular system.", "content": "The remote effects of cancer on the neuromuscular system include type II muscle fiber atrophy, dermatomyositis/polymyositis, myasthenia gravis, the facilitating myasthenic syndrome, peripheral neuropathy (including amyloid neuropathy), and possibly amyotrophic lateral sclerosis. The clinical and pathological findings and a number of possible pathokinetic mechanisms of these disorders are discussed. In none is the pathokinetic mechanism known. Hence, much work remains in therapeutically oriented research of the mechanisms in all of the remote effects of cancer on the neuromuscular system.", "contents": "Remote effects of focal cancer on the neuromuscular system. The remote effects of cancer on the neuromuscular system include type II muscle fiber atrophy, dermatomyositis/polymyositis, myasthenia gravis, the facilitating myasthenic syndrome, peripheral neuropathy (including amyloid neuropathy), and possibly amyotrophic lateral sclerosis. The clinical and pathological findings and a number of possible pathokinetic mechanisms of these disorders are discussed. In none is the pathokinetic mechanism known. Hence, much work remains in therapeutically oriented research of the mechanisms in all of the remote effects of cancer on the neuromuscular system."} {"id": "PMID:180777", "title": "Role of radiation therapy in the management of neoplasms of the central nervous system.", "content": "Radiation therapy plays an important role as an adjunctive treatment modality with surgery and/or chemotherapy in a number of primary and secondary CNS neoplasms, including glioblastoma multiforme, lower grade gliomas, brainstem tumors, medulloblastoma, ependymoma, most pituitary and parapituitary tumors, brain metastases, and epidural spinal cord metastases; it also has an important function in the total management of childhood leukemia. Radiation therapy can also be extremely effective as the primary or sole treatment of pituitary adenomas, craniopharyngioma, and cerebral and epidural metastases. The relative roles of, and indications for, surgery versus irradiation have been discussed. There is clearly a need for more information regarding the natural history relative response of specific tumors to the various therapeutic modalities available, as well as the most effective and safe ways to combine treatments. To this end, it is mandatory that surgeons, radiotherapists, neurologists, pathologists, and internists begin to intercommunicate more freely and objectively. Hopefully, in areas that continue to be controversial, well-designed clinical trials can begin to furnish the necessary answers. This is particularly relevant as all of the disciplines mentioned are developing newer and hopefully more effective diagnostic and therapeutic capabilities.", "contents": "Role of radiation therapy in the management of neoplasms of the central nervous system. Radiation therapy plays an important role as an adjunctive treatment modality with surgery and/or chemotherapy in a number of primary and secondary CNS neoplasms, including glioblastoma multiforme, lower grade gliomas, brainstem tumors, medulloblastoma, ependymoma, most pituitary and parapituitary tumors, brain metastases, and epidural spinal cord metastases; it also has an important function in the total management of childhood leukemia. Radiation therapy can also be extremely effective as the primary or sole treatment of pituitary adenomas, craniopharyngioma, and cerebral and epidural metastases. The relative roles of, and indications for, surgery versus irradiation have been discussed. There is clearly a need for more information regarding the natural history relative response of specific tumors to the various therapeutic modalities available, as well as the most effective and safe ways to combine treatments. To this end, it is mandatory that surgeons, radiotherapists, neurologists, pathologists, and internists begin to intercommunicate more freely and objectively. Hopefully, in areas that continue to be controversial, well-designed clinical trials can begin to furnish the necessary answers. This is particularly relevant as all of the disciplines mentioned are developing newer and hopefully more effective diagnostic and therapeutic capabilities."} {"id": "PMID:180786", "title": "The use of electromyography in angiology.", "content": "The author of the present study examined electric activity of the muscle in three types of chronic arterial occlusions, i.e. in obliterating atherosclerosis, obliterating thromboangiitis and diabetic angiopathy. He obtained two different electromyographic patterns. One, present in patients suffering from obliterating atherosclerosis, showed signs of a peripheral nerve-damage (characterized by broad action-potentials) and another, found in patients with obliterating thromboangiitis and in diabetics suffering from diabetic angiopathy, with a pattern corresponding to a combined injury--of impaired muscle-fibre and peripheral nerve (characterized by pathological action-potentials of short and long duration). The last group could be further divided into a subgroup where both electromyographic lesions were distinctly noted, comprising patients with obliterating thromboangiitis, and another subgroup, clearly characterized by primary myogenic disorder with a milder disturbance of peripheral nerves. The last subgroup consisted of diabetic patients suffering from diabetic angiopathy. According to the author's suggestion, the divergence in electromyographic patterns in individual diseases of peripheral arteries may be conditioned by different in individual diseases of peripheral arteries, may be conditioned by different localisations of arterial occlusions. Various preferential levels of arterial occlusions give to various diseases a different clinical, as well as electromyographical feature. Neurogenic findings in obliterating atherosclerosis is determined by occlusions of large arteries. From these vessels afferent branches divert for the nutritive supply of the nerve-trunk of the leg. This results in ischaemic lesions of nervous fibers of various degrees in the leg. In the periphery a total of fine or gross changes may be registered on the electomyogram--as a sign of a peripheral nervous lesion. Electromyographic pattern of obliterating thromboangiitis reveals changes similar to those of obliterating atherosclerosis--namely a picture of a peripheral nervous lesion--but in addition there appear regular changes indicating a primarilly muscle impairment. The interpretation means that nervous impairment is present. In fact, no occlusions of the main arteries take place at the level of the diverted nutrient branches of the nerve-trunk, but obliterating thromboangiitis, affecting small and medium vessels, presses the occlusions more proximally to the nervous trunk. The final result and effect is the same and in more severe instances even more striking. Nutrient muscle-arteries, being vessels of medium caliber, are obturated--in cases of obliterating thromboangiitis--commonly with main trunks in the tibial and foot-zone. Possibilities of a collateral circulation in instances where medium and small arteries are obturated, are worse than in large artery-occlusions and the blood-flow becomes more impaired. Realizing the adjacent diffuse affection of arteriolar muscle-net, we get a picture described by Scalabrino and Bianchi...", "contents": "The use of electromyography in angiology. The author of the present study examined electric activity of the muscle in three types of chronic arterial occlusions, i.e. in obliterating atherosclerosis, obliterating thromboangiitis and diabetic angiopathy. He obtained two different electromyographic patterns. One, present in patients suffering from obliterating atherosclerosis, showed signs of a peripheral nerve-damage (characterized by broad action-potentials) and another, found in patients with obliterating thromboangiitis and in diabetics suffering from diabetic angiopathy, with a pattern corresponding to a combined injury--of impaired muscle-fibre and peripheral nerve (characterized by pathological action-potentials of short and long duration). The last group could be further divided into a subgroup where both electromyographic lesions were distinctly noted, comprising patients with obliterating thromboangiitis, and another subgroup, clearly characterized by primary myogenic disorder with a milder disturbance of peripheral nerves. The last subgroup consisted of diabetic patients suffering from diabetic angiopathy. According to the author's suggestion, the divergence in electromyographic patterns in individual diseases of peripheral arteries may be conditioned by different in individual diseases of peripheral arteries, may be conditioned by different localisations of arterial occlusions. Various preferential levels of arterial occlusions give to various diseases a different clinical, as well as electromyographical feature. Neurogenic findings in obliterating atherosclerosis is determined by occlusions of large arteries. From these vessels afferent branches divert for the nutritive supply of the nerve-trunk of the leg. This results in ischaemic lesions of nervous fibers of various degrees in the leg. In the periphery a total of fine or gross changes may be registered on the electomyogram--as a sign of a peripheral nervous lesion. Electromyographic pattern of obliterating thromboangiitis reveals changes similar to those of obliterating atherosclerosis--namely a picture of a peripheral nervous lesion--but in addition there appear regular changes indicating a primarilly muscle impairment. The interpretation means that nervous impairment is present. In fact, no occlusions of the main arteries take place at the level of the diverted nutrient branches of the nerve-trunk, but obliterating thromboangiitis, affecting small and medium vessels, presses the occlusions more proximally to the nervous trunk. The final result and effect is the same and in more severe instances even more striking. Nutrient muscle-arteries, being vessels of medium caliber, are obturated--in cases of obliterating thromboangiitis--commonly with main trunks in the tibial and foot-zone. Possibilities of a collateral circulation in instances where medium and small arteries are obturated, are worse than in large artery-occlusions and the blood-flow becomes more impaired. Realizing the adjacent diffuse affection of arteriolar muscle-net, we get a picture described by Scalabrino and Bianchi..."} {"id": "PMID:180787", "title": "Personal air sampling for vapors of aniline compounds.", "content": "A method has been developed for air sampling and laboratory analysis of vapors of seven aniline compounds: aniline, N,N-dimethylaniline, o-toluidine, 2,4-xylidine, panisidine, o-anisidine, and p-nitroaniline. Air is drawn by a personal sampling pump from a worker's breathing zone through a tube containing silica gel to collect any anilines present. In the laboratory each silica gel section is transferred to a glass-stoppered tube and desorbed with ethanol. An aliquot of this is analyzed by gas chromatography to determine the amount of each aniline compound present. The sampling tube can be used for short-term sampling at 1000 cm3/min or for sampling up to eight hours at 200 cm3/min. Maximum interference effects of water vapor have been considered. Results of retention, desorption, storage, accuracy, and precision studies are presented.", "contents": "Personal air sampling for vapors of aniline compounds. A method has been developed for air sampling and laboratory analysis of vapors of seven aniline compounds: aniline, N,N-dimethylaniline, o-toluidine, 2,4-xylidine, panisidine, o-anisidine, and p-nitroaniline. Air is drawn by a personal sampling pump from a worker's breathing zone through a tube containing silica gel to collect any anilines present. In the laboratory each silica gel section is transferred to a glass-stoppered tube and desorbed with ethanol. An aliquot of this is analyzed by gas chromatography to determine the amount of each aniline compound present. The sampling tube can be used for short-term sampling at 1000 cm3/min or for sampling up to eight hours at 200 cm3/min. Maximum interference effects of water vapor have been considered. Results of retention, desorption, storage, accuracy, and precision studies are presented."} {"id": "PMID:180788", "title": "Vitamin B12 levels and nerve conduction velocities in patients undergoing maintenance hemodialysis.", "content": "Serum vitamin B12 concentrations were measured in 60 patients undergoing repetitive hemodialysis and in undialyzed patients with chronic renal failure. Dialysis patients had significantly lower serum vitamin B12 levels than the nondialyzed group 321 +/- SEM 38 pg/ml versus 793 +/- 100), and 19 of 60 dialysis patients had vitamin B12 Concentrations less than 200 pg/ml. Folic acid concentration was 5 times greater in dialysis than in nondialysis patients, presumably because the latter received daily supplementation with folic acid. Serum vitamin B12 concentrations fell progressively during the patient's course of dialysis. Neither inadequate dietary intake nor vitamin B12 malabsorption accounted for the differences in the serum vitamin B12 concentrations seen in the two groups. Serum vitamin B12 levels and nerve conduction velocities in 51 dialyzed patients showed a significant correlation. Six dialyzed patients with low serum vitamin B12 levels and slow nerve conduction velocities showed improvement in nerve conduction (+ 14.6 +/- 3.3 m/sec) following the parenteral use of pharmacological doses of vitamin B12. The cause of the low serum vitamin B12 concentration is not clear, nevertheless, alterations in serum vitamin B12 seen in some dialysis patients may be a factor in the persistence of abnormal nerve conduction and may be reversed with large doses of parenteral vitamin B12.", "contents": "Vitamin B12 levels and nerve conduction velocities in patients undergoing maintenance hemodialysis. Serum vitamin B12 concentrations were measured in 60 patients undergoing repetitive hemodialysis and in undialyzed patients with chronic renal failure. Dialysis patients had significantly lower serum vitamin B12 levels than the nondialyzed group 321 +/- SEM 38 pg/ml versus 793 +/- 100), and 19 of 60 dialysis patients had vitamin B12 Concentrations less than 200 pg/ml. Folic acid concentration was 5 times greater in dialysis than in nondialysis patients, presumably because the latter received daily supplementation with folic acid. Serum vitamin B12 concentrations fell progressively during the patient's course of dialysis. Neither inadequate dietary intake nor vitamin B12 malabsorption accounted for the differences in the serum vitamin B12 concentrations seen in the two groups. Serum vitamin B12 levels and nerve conduction velocities in 51 dialyzed patients showed a significant correlation. Six dialyzed patients with low serum vitamin B12 levels and slow nerve conduction velocities showed improvement in nerve conduction (+ 14.6 +/- 3.3 m/sec) following the parenteral use of pharmacological doses of vitamin B12. The cause of the low serum vitamin B12 concentration is not clear, nevertheless, alterations in serum vitamin B12 seen in some dialysis patients may be a factor in the persistence of abnormal nerve conduction and may be reversed with large doses of parenteral vitamin B12."} {"id": "PMID:180789", "title": "Vitamin B6 nutriture of children with acute celiac disease, celiac disease in remission, and of children with normal duodenal mucosa.", "content": "Patients with adult celiac disease excrete abnormal amounts of tryptophan metabolites after loading with this amino acid, suggesting vitamin B6 deficienty in these patients, In fact, the excretion of tryptophan metabolites returns to normal after administration of vitamin B6. The vitamin B6 nutriture was measured by means of determination of pyridoxal phosphate and activity of pyridoxalkinase in serum and in duodenal mucosa of 14 children with acute celiac disease and of six children with celiac disease in clinical and biochemical remission. Ten children with normal duodenal mucosa were studied as controls. Children with celiac disease had significantly decreased pyridoxal phosphate in serum and in duodenal mucosa when compared both with children in remission and controls. Activity of pyridoxalkinase, however, was significantly increased in serum and in duodenal mucosa when compared with controls but not when compared with children in remission. These children had the same increase in pyridoxalkinase activity as children with acute celiac disease. These data provide a strong evidence for the occurrence of vitamin B6 deficienty in children with acute celiac disease. The children with celiac disease in remission still had an increased activity of pyridoxalkinase which seems to be a compensating mechanism in consequence of vitamin B6 deficiency prior to the gluten-free diet.", "contents": "Vitamin B6 nutriture of children with acute celiac disease, celiac disease in remission, and of children with normal duodenal mucosa. Patients with adult celiac disease excrete abnormal amounts of tryptophan metabolites after loading with this amino acid, suggesting vitamin B6 deficienty in these patients, In fact, the excretion of tryptophan metabolites returns to normal after administration of vitamin B6. The vitamin B6 nutriture was measured by means of determination of pyridoxal phosphate and activity of pyridoxalkinase in serum and in duodenal mucosa of 14 children with acute celiac disease and of six children with celiac disease in clinical and biochemical remission. Ten children with normal duodenal mucosa were studied as controls. Children with celiac disease had significantly decreased pyridoxal phosphate in serum and in duodenal mucosa when compared both with children in remission and controls. Activity of pyridoxalkinase, however, was significantly increased in serum and in duodenal mucosa when compared with controls but not when compared with children in remission. These children had the same increase in pyridoxalkinase activity as children with acute celiac disease. These data provide a strong evidence for the occurrence of vitamin B6 deficienty in children with acute celiac disease. The children with celiac disease in remission still had an increased activity of pyridoxalkinase which seems to be a compensating mechanism in consequence of vitamin B6 deficiency prior to the gluten-free diet."} {"id": "PMID:180790", "title": "Decreased interferon production by leukocytes in marasmus.", "content": "Interferon production by leukocytes in culture was investigated in nine severely marasmic infants and 31 well-nourished controls. The production of interferon was induced with Newcastle disease virus and assayed in Vero cells challenged with vesicular stomatitis virus. Marasmic infants produced significantly less interferon than controls. It is suggested that the finding may be the result of a lymphocyte defect induced by malnutrition and could help to explain the increased frequency and severity of viral diseases in this condition.", "contents": "Decreased interferon production by leukocytes in marasmus. Interferon production by leukocytes in culture was investigated in nine severely marasmic infants and 31 well-nourished controls. The production of interferon was induced with Newcastle disease virus and assayed in Vero cells challenged with vesicular stomatitis virus. Marasmic infants produced significantly less interferon than controls. It is suggested that the finding may be the result of a lymphocyte defect induced by malnutrition and could help to explain the increased frequency and severity of viral diseases in this condition."} {"id": "PMID:180791", "title": "Potential anti-fertility plants from Chinese medicine.", "content": "A brief review of the history of development of Chinese pharmacognosy and its application to gynecology and obstetrics is presented. An evaluation system is introduced for short-listing some potentially useful and anti-fertility plants. Twenty such plants are listed in order of priority according to our evaluation system. Brief descriptions of the botany, phytochemistry and reputed biological effects are provided. It is hoped that this article may provide an impetus for the development of new antifertility agents.", "contents": "Potential anti-fertility plants from Chinese medicine. A brief review of the history of development of Chinese pharmacognosy and its application to gynecology and obstetrics is presented. An evaluation system is introduced for short-listing some potentially useful and anti-fertility plants. Twenty such plants are listed in order of priority according to our evaluation system. Brief descriptions of the botany, phytochemistry and reputed biological effects are provided. It is hoped that this article may provide an impetus for the development of new antifertility agents."} {"id": "PMID:180792", "title": "Giant lymph-node hyperplasia, plasma-cell type, of the mediastinum, with peripheral neuropathy.", "content": "A case of mediastinal giant lymph-node hyperplasia, plasma-cell type, is described. The patient had progressive peripheral neuropathy for which no apparent cause was found. Giant lymph-node hyperplasia with associated peripheral neuropathy has not been reported previously.", "contents": "Giant lymph-node hyperplasia, plasma-cell type, of the mediastinum, with peripheral neuropathy. A case of mediastinal giant lymph-node hyperplasia, plasma-cell type, is described. The patient had progressive peripheral neuropathy for which no apparent cause was found. Giant lymph-node hyperplasia with associated peripheral neuropathy has not been reported previously."} {"id": "PMID:180793", "title": "The use of human foreskin cell cultures for isolation of herpesvirus group in the diagnostic laboratory.", "content": "Cell cultures originated from human foreskin (HFS) tissues were used for isolation of viruses from diagnostic specimens. The foreskins were collected in Hank's balanced salt solution and then processed on the same day by dispersion in trypsin. A week after the trypsin treatment of the tissues, the first cell cultures were ready to use. Continuous subcultures in vitro of the cells gave rise to a colony of cells that multiplied freely in vitro and supported the growth of viruses from the herpes group. In three cases tested in our laboratory in the last 6 months, viruses from the herpes group were isolated on the HES. The cytopathic changes of the HFS cells were observed 5 to 8 days after infection. They were not detected on two other human-origin cell cultures (WI-38 and HEp2) or on primary monkey kidney cells. The viruses isolated from these three cases were cytomegalovirus (CMV) from urine of a 2-week-old baby, a second CMV from a cutaneous lesion of a renal-transplant patient and herpes simplex virus from the eye swab of a young girl. After a few subcultures on the HFS cells, the three viruses produced CPE on the other susceptible human cells. The preparation of HFS cells is easy, the availability of the tissue is high, and the diagnostic value is unquestionable. It is suggested that this tissue and its cell cultures be used more often in diagnostic and research laboratories.", "contents": "The use of human foreskin cell cultures for isolation of herpesvirus group in the diagnostic laboratory. Cell cultures originated from human foreskin (HFS) tissues were used for isolation of viruses from diagnostic specimens. The foreskins were collected in Hank's balanced salt solution and then processed on the same day by dispersion in trypsin. A week after the trypsin treatment of the tissues, the first cell cultures were ready to use. Continuous subcultures in vitro of the cells gave rise to a colony of cells that multiplied freely in vitro and supported the growth of viruses from the herpes group. In three cases tested in our laboratory in the last 6 months, viruses from the herpes group were isolated on the HES. The cytopathic changes of the HFS cells were observed 5 to 8 days after infection. They were not detected on two other human-origin cell cultures (WI-38 and HEp2) or on primary monkey kidney cells. The viruses isolated from these three cases were cytomegalovirus (CMV) from urine of a 2-week-old baby, a second CMV from a cutaneous lesion of a renal-transplant patient and herpes simplex virus from the eye swab of a young girl. After a few subcultures on the HFS cells, the three viruses produced CPE on the other susceptible human cells. The preparation of HFS cells is easy, the availability of the tissue is high, and the diagnostic value is unquestionable. It is suggested that this tissue and its cell cultures be used more often in diagnostic and research laboratories."} {"id": "PMID:180797", "title": "Hypergastrinemia induced by glucocorticoid and corticotropin treatment in man.", "content": "To elucidate further the pathogenesis of steroid-induced ulceration, plasma gastrin levels, both basal and after a test meal, were studied in normal volunteers and patients treated with glucocorticoids or corticotropin. In normal subjects the acute intravenous administration of 100 mg prednisolone had no effect on plasma gastrin levels. After oral administration of prednisolone (40 mg daily, for four days) a significant increase of the basal, the reactive, and the over 90-min integrated gastrin release was observed. In this group, the glucocorticoid treatment had a slight, but significant influence on gastric acid and pepsin secretion, while acidity and pepsin output stimulated by pentagastrin was not affected. In patients treated with prednisolone for more than 24 weeks, the oral administration of this hormone failed to alter basal gastrin values but affected significantly secretion after the test meal. In patients with multiple sclerosis, after intramuscular administration of corticotropin (60 IU daily, for 12 days), an increase of the basal, the reactive, and the integrated gastrin release also was found. Glucocorticoid-induced hypergastrinemia provides information on the pathogenesis of steroid-induced ulceration.", "contents": "Hypergastrinemia induced by glucocorticoid and corticotropin treatment in man. To elucidate further the pathogenesis of steroid-induced ulceration, plasma gastrin levels, both basal and after a test meal, were studied in normal volunteers and patients treated with glucocorticoids or corticotropin. In normal subjects the acute intravenous administration of 100 mg prednisolone had no effect on plasma gastrin levels. After oral administration of prednisolone (40 mg daily, for four days) a significant increase of the basal, the reactive, and the over 90-min integrated gastrin release was observed. In this group, the glucocorticoid treatment had a slight, but significant influence on gastric acid and pepsin secretion, while acidity and pepsin output stimulated by pentagastrin was not affected. In patients treated with prednisolone for more than 24 weeks, the oral administration of this hormone failed to alter basal gastrin values but affected significantly secretion after the test meal. In patients with multiple sclerosis, after intramuscular administration of corticotropin (60 IU daily, for 12 days), an increase of the basal, the reactive, and the integrated gastrin release also was found. Glucocorticoid-induced hypergastrinemia provides information on the pathogenesis of steroid-induced ulceration."} {"id": "PMID:180798", "title": "Gastric xanthoma.", "content": "Gastric xanthoma (GX) consists of a small yellowish lesion of the gastric mucosa, frequently of multiple occurrence; histologically, there is an accumulation of lipid-laden histiocytes in the lamina propria. Seven cases are reported. One patient also had jejunal localizations. There is no correlation with hypercholesterolemia but in four cases a slight hypertriglyceridemia was found. A control gastroscopy, performed in four cases, revealed no changes in the first patient but a decrease in size in a second and the disappearance of GX in two other patients.", "contents": "Gastric xanthoma. Gastric xanthoma (GX) consists of a small yellowish lesion of the gastric mucosa, frequently of multiple occurrence; histologically, there is an accumulation of lipid-laden histiocytes in the lamina propria. Seven cases are reported. One patient also had jejunal localizations. There is no correlation with hypercholesterolemia but in four cases a slight hypertriglyceridemia was found. A control gastroscopy, performed in four cases, revealed no changes in the first patient but a decrease in size in a second and the disappearance of GX in two other patients."} {"id": "PMID:180799", "title": "Benign granular cell tumor (\"myoblastoma\") of the stomach.", "content": "Two cases of benign granular cell tumor of the stomach which were found incidentally are reported. A review of the literature disclosed 10 case reports and three other cases which were mentioned. Despite the small size of the tumors eight of the 10 cases produced gastrointestinal signs or symptoms. A brief discussion of the histogenesis of the lesion is presented.", "contents": "Benign granular cell tumor (\"myoblastoma\") of the stomach. Two cases of benign granular cell tumor of the stomach which were found incidentally are reported. A review of the literature disclosed 10 case reports and three other cases which were mentioned. Despite the small size of the tumors eight of the 10 cases produced gastrointestinal signs or symptoms. A brief discussion of the histogenesis of the lesion is presented."} {"id": "PMID:180800", "title": "Endemic amebiasis in an Arkansas community.", "content": "Parasitologic, serologic, and epidemiologic studies were done during 1967 in Calion, Arkansas (population 544). Infection with Entamoeba histolytica was found to be endemic but was segregated along racial lines. Twenty-two (9.9%) black compared with only one (0.6%) white had E. histolytica demonstrated in one stool examination; only two blacks had symptoms suggestive of amebiasis. No positive amebiasis indirect hemaggulination titers were found in 135 white residents. In contrast, 41 (17.9%) blacks had positive titers. Age, sex, and geographic location were not associated with stool or seropositivity. Within the black population, clustering of stool and seropositivity occurred. Significantly higher rates of stool and seropositivity were seen in households with crowding and poor sanitation as evidenced by lack of indoor toilet facilities. The presence of contaminated water supplies did not correlate with stool or seropositivity. The probable importance of person-to-person transmission is suggested by the observed clustering of infection within households with crowding and unsanitary conditions. The absence of evidence for transmission by food or water further supports this hypothesis.", "contents": "Endemic amebiasis in an Arkansas community. Parasitologic, serologic, and epidemiologic studies were done during 1967 in Calion, Arkansas (population 544). Infection with Entamoeba histolytica was found to be endemic but was segregated along racial lines. Twenty-two (9.9%) black compared with only one (0.6%) white had E. histolytica demonstrated in one stool examination; only two blacks had symptoms suggestive of amebiasis. No positive amebiasis indirect hemaggulination titers were found in 135 white residents. In contrast, 41 (17.9%) blacks had positive titers. Age, sex, and geographic location were not associated with stool or seropositivity. Within the black population, clustering of stool and seropositivity occurred. Significantly higher rates of stool and seropositivity were seen in households with crowding and poor sanitation as evidenced by lack of indoor toilet facilities. The presence of contaminated water supplies did not correlate with stool or seropositivity. The probable importance of person-to-person transmission is suggested by the observed clustering of infection within households with crowding and unsanitary conditions. The absence of evidence for transmission by food or water further supports this hypothesis."} {"id": "PMID:180801", "title": "The nephrotic syndrome associated with neoplasia: an unusual paraneoplastic syndrome. Report of a case and review of the literature.", "content": "The nephrotic syndrome complicating malignancy in the absence of renal vein thrombosis, amyloid or neoplastic infiltration of the kidney is an unusual occurrence. A case of diffuse, well differentiated, lymphocytic lymphoma and lipoid nephrosis documented by light microscopy, electron microscopy and immunofluorescent studies is reported. A review of the literature revealed 76 case reports in which the nephrotic syndrome was associated with neoplasia. The most frequently associated neoplasms are Hodgkin's disease, various carcinomas, nonHodgkin's lymphoma and leukemia in descending order. The most frequent renal lesion in patients with the nephrotic syndrome associated with various carcinomas is membranous glomerulonephritis (81 per cent) as opposed to patients with lymphomas or leukemias who have predominantly lipoid nephrosis (60 per cent). The evidence is reviewed suggesting that the lesions in membranous nephropathy are immunologically mediated by tumor or viral antigen-antibody complexes and in lipoid nephrosis perhaps by a defect in t-lymphocyte function.", "contents": "The nephrotic syndrome associated with neoplasia: an unusual paraneoplastic syndrome. Report of a case and review of the literature. The nephrotic syndrome complicating malignancy in the absence of renal vein thrombosis, amyloid or neoplastic infiltration of the kidney is an unusual occurrence. A case of diffuse, well differentiated, lymphocytic lymphoma and lipoid nephrosis documented by light microscopy, electron microscopy and immunofluorescent studies is reported. A review of the literature revealed 76 case reports in which the nephrotic syndrome was associated with neoplasia. The most frequently associated neoplasms are Hodgkin's disease, various carcinomas, nonHodgkin's lymphoma and leukemia in descending order. The most frequent renal lesion in patients with the nephrotic syndrome associated with various carcinomas is membranous glomerulonephritis (81 per cent) as opposed to patients with lymphomas or leukemias who have predominantly lipoid nephrosis (60 per cent). The evidence is reviewed suggesting that the lesions in membranous nephropathy are immunologically mediated by tumor or viral antigen-antibody complexes and in lipoid nephrosis perhaps by a defect in t-lymphocyte function."} {"id": "PMID:180802", "title": "Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome).", "content": "A 25 year old patient with congenital hypoplastic anemia (Black-fan-Diamond syndrome) is described. This patient was hepatitis-antigen negative, had not received androgens and had a hepatoma develop in a transfusional hemochromatotic liver. Since androgens have been associated with hepatocellular carcinoma, the use of androgenic steroids for other than life-threatening symptoms in this disease should be avoided.", "contents": "Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome). A 25 year old patient with congenital hypoplastic anemia (Black-fan-Diamond syndrome) is described. This patient was hepatitis-antigen negative, had not received androgens and had a hepatoma develop in a transfusional hemochromatotic liver. Since androgens have been associated with hepatocellular carcinoma, the use of androgenic steroids for other than life-threatening symptoms in this disease should be avoided."} {"id": "PMID:180803", "title": "Cyclic adenosine 3',5'-monophosphate (cAMP) in pregnancy body fluids during normal and abnormal pregnancy.", "content": "cAMP levels in maternal urine (MU), maternal plasma (MP), and amniotic fluid (AF) were measured by competitive protein-binding assay in medically uncomplicated pregnancies (Group A) and some abnormal pregnancies (Group B). In Group A, MU values increased from 3.43 +/- 0.3 mu/Moles per gram of creatinine (mean +/- S.E.M.) at 12 to 29 weeks to its peak value, 5.72 +/- 1.03 at 33 to 35 weeks (p less than 0.025). Thereafter, the values decreased until term. In AF, cAMP levels increased from 9.4 +/- 1.02 at 10 to 19 weeks to 32.6 +/- 2.7 picomoles per milliliter between 35 and 42 weeks (p less than 0.005). Mean +/- S.E.M. MP levels between 4 to 20 and 21 to 42 weeks showed no significant difference (14.97 +/- 15.89 +/- 0.57 picomoles per milliliter, respectively). Umbilical cord plasma contained higher concentrations than in MP and AF. In Group B, abnormal MU patterns were observed in hypertensive disorders, chronic renal disease, and postmaturity. In a single patient with hyperthyroidism, abnormal MU and AF (but not MP) levels were observed. Abnormalities in MU and AF concentrations of the nucleotide are thus not specific for one disease entity.", "contents": "Cyclic adenosine 3',5'-monophosphate (cAMP) in pregnancy body fluids during normal and abnormal pregnancy. cAMP levels in maternal urine (MU), maternal plasma (MP), and amniotic fluid (AF) were measured by competitive protein-binding assay in medically uncomplicated pregnancies (Group A) and some abnormal pregnancies (Group B). In Group A, MU values increased from 3.43 +/- 0.3 mu/Moles per gram of creatinine (mean +/- S.E.M.) at 12 to 29 weeks to its peak value, 5.72 +/- 1.03 at 33 to 35 weeks (p less than 0.025). Thereafter, the values decreased until term. In AF, cAMP levels increased from 9.4 +/- 1.02 at 10 to 19 weeks to 32.6 +/- 2.7 picomoles per milliliter between 35 and 42 weeks (p less than 0.005). Mean +/- S.E.M. MP levels between 4 to 20 and 21 to 42 weeks showed no significant difference (14.97 +/- 15.89 +/- 0.57 picomoles per milliliter, respectively). Umbilical cord plasma contained higher concentrations than in MP and AF. In Group B, abnormal MU patterns were observed in hypertensive disorders, chronic renal disease, and postmaturity. In a single patient with hyperthyroidism, abnormal MU and AF (but not MP) levels were observed. Abnormalities in MU and AF concentrations of the nucleotide are thus not specific for one disease entity."} {"id": "PMID:180804", "title": "Phosphatidylinositol and phosphatidylglycerol in amniotic fluid: indices of lung maturity.", "content": "The minor phospholipids in amniotic fluid from normal pregnancies were correlated with the well-established index of lung maturity, the lecithin/sphingomyelin (L/S) ratio. When the L/S ratio was less than 1.0, the acidic phospholippids phosphatidylglycerol (PG) and phosphatidylinositol (PI) were absent or low in concentration (0.0 to 2.5 per cent of lipid phosphorus). Parallel to the increase in the L/S ratio to 2.0, the content of PI increased 6.0 to 8.5 per cent of lipid phosphorus. PG, the unique phospholipid of lung surfactant, first appeared and PI concomitantly decreased when the L/S ratio exceeded 2.0, indicating the secretion of mature lung surfactant. Analysis of PI and PG in amniotic fluid as markers of surfactant seems to be of value as an additional index of prenatal evaluation of lung maturity and may be particularly useful when the specimen is contaminated with blood.", "contents": "Phosphatidylinositol and phosphatidylglycerol in amniotic fluid: indices of lung maturity. The minor phospholipids in amniotic fluid from normal pregnancies were correlated with the well-established index of lung maturity, the lecithin/sphingomyelin (L/S) ratio. When the L/S ratio was less than 1.0, the acidic phospholippids phosphatidylglycerol (PG) and phosphatidylinositol (PI) were absent or low in concentration (0.0 to 2.5 per cent of lipid phosphorus). Parallel to the increase in the L/S ratio to 2.0, the content of PI increased 6.0 to 8.5 per cent of lipid phosphorus. PG, the unique phospholipid of lung surfactant, first appeared and PI concomitantly decreased when the L/S ratio exceeded 2.0, indicating the secretion of mature lung surfactant. Analysis of PI and PG in amniotic fluid as markers of surfactant seems to be of value as an additional index of prenatal evaluation of lung maturity and may be particularly useful when the specimen is contaminated with blood."} {"id": "PMID:180805", "title": "Serum unconjugated estriol levels in the third trimester and their relationship to gestational age.", "content": "Maternal unconjugated estriol levels were measured throughout the 28 to 41 week interval in two groups of accurately dated normal pregnancies. The first group consisted of randomly sampled pregnancies on which 285 unconjugated estriol determinations were performed. The logarithms of the mean values plotted into a positive sloping, relatively straight line which was disrupted by a plateau originating at 31 to 32 weeks and terminated at 35 weeks where there began a steep surge to a point at 36 weeks (surge point) that returned values to fit the previously established straight line. To investigate these findings in individual pregnancies, a second group of nine subjects was studied with serial unconjugated estriol determinations. In all nine of these subjects, the surge point could be identified statistically and occurred at a mean gestational age of 36.0 +/- 0.6 (1 S.D.) weeks. Data from the first group of randomly sampled pregnancies indicate that the surge point occurred around a mean gestational age of 36.0 weeks and was confirmed by data from the second group of serially sampled individual subjects showing the surge point as a statistically definable marker in normal pregnancies.", "contents": "Serum unconjugated estriol levels in the third trimester and their relationship to gestational age. Maternal unconjugated estriol levels were measured throughout the 28 to 41 week interval in two groups of accurately dated normal pregnancies. The first group consisted of randomly sampled pregnancies on which 285 unconjugated estriol determinations were performed. The logarithms of the mean values plotted into a positive sloping, relatively straight line which was disrupted by a plateau originating at 31 to 32 weeks and terminated at 35 weeks where there began a steep surge to a point at 36 weeks (surge point) that returned values to fit the previously established straight line. To investigate these findings in individual pregnancies, a second group of nine subjects was studied with serial unconjugated estriol determinations. In all nine of these subjects, the surge point could be identified statistically and occurred at a mean gestational age of 36.0 +/- 0.6 (1 S.D.) weeks. Data from the first group of randomly sampled pregnancies indicate that the surge point occurred around a mean gestational age of 36.0 weeks and was confirmed by data from the second group of serially sampled individual subjects showing the surge point as a statistically definable marker in normal pregnancies."} {"id": "PMID:180806", "title": "Limitation of the specific serum radioimmunoassay for human chorionic gonadotropin in the management of trophoblastic neoplasms.", "content": "Two cases of recurrent trophoblastic disease are presented in which human chorionic gonadotropin was detected in assays of urine concentrates at a time when serum levels were undetectable by a sensitive and specific beta-subunit radioimmunoassay. The potential greater usefulness of measurements of urinary concentrates is discussed.", "contents": "Limitation of the specific serum radioimmunoassay for human chorionic gonadotropin in the management of trophoblastic neoplasms. Two cases of recurrent trophoblastic disease are presented in which human chorionic gonadotropin was detected in assays of urine concentrates at a time when serum levels were undetectable by a sensitive and specific beta-subunit radioimmunoassay. The potential greater usefulness of measurements of urinary concentrates is discussed."} {"id": "PMID:180807", "title": "The androgenic polycystic ovary.", "content": "The polycystic ovary has the capacity to produce excessive androgens (delta4-androstenedione, dehydroepiandrosterone, and testosterone). Whether this disorder is caused by constant pituitary priming of the ovaries due to hypothalamic-pituitary derangement or an ovarian enzyme defect, the end result is the same, i.e., abnormal androgen production. In an effort to explain the syndrome, we offer the hypothesis of an inherently sensitized adrenal secreting excessive androgen which leads to an imbalance in the hypothalamic-pituitary axia. The result is a tonic stimulation of the ovaries eventuating in \"the androgenic polycystic ovary.\"", "contents": "The androgenic polycystic ovary. The polycystic ovary has the capacity to produce excessive androgens (delta4-androstenedione, dehydroepiandrosterone, and testosterone). Whether this disorder is caused by constant pituitary priming of the ovaries due to hypothalamic-pituitary derangement or an ovarian enzyme defect, the end result is the same, i.e., abnormal androgen production. In an effort to explain the syndrome, we offer the hypothesis of an inherently sensitized adrenal secreting excessive androgen which leads to an imbalance in the hypothalamic-pituitary axia. The result is a tonic stimulation of the ovaries eventuating in \"the androgenic polycystic ovary.\""} {"id": "PMID:180808", "title": "Assay of estriol-16alpha-(beta-D-glucuronide) in pregnancy urine with a specific antiserum.", "content": "A rapid, direct radioimmunoassay for estriol-16alpha-(beta-D-glucuronide) in pregnancy urine has been developed by use of immunogens in which the estriol glucuronide hapten is linked through positions 2 or 4 of ring A to bovine serum albumin or agarose gel. The resultant antibodies cross react less than 1% with other estriol conjugates, estradiol conjugates, or unconjugated estrogens. Pregnanediol-3-glucuronide cross reacts less than 0.5%. This high degree of specificity of the antibodies allows for a 10,000-fold dilution of pregnancy urine to be assayed directly without interference from other steroids or urinary constituents. Good linear correlation was obtained for urinary-estriol glucuronide equivalents measured in the same subjects by our routine colorimetric method which separates and measures free estriol after hydrolysis. With an accelerated antibody-antigen equilibration of 20 minutes at 40 degrees, 10 samples can be easily processed in less than 90 minutes. The method also allows for the evaluation of variations in the excretion pattern of one estrogen conjugate in normal and high-risk pregnancies.", "contents": "Assay of estriol-16alpha-(beta-D-glucuronide) in pregnancy urine with a specific antiserum. A rapid, direct radioimmunoassay for estriol-16alpha-(beta-D-glucuronide) in pregnancy urine has been developed by use of immunogens in which the estriol glucuronide hapten is linked through positions 2 or 4 of ring A to bovine serum albumin or agarose gel. The resultant antibodies cross react less than 1% with other estriol conjugates, estradiol conjugates, or unconjugated estrogens. Pregnanediol-3-glucuronide cross reacts less than 0.5%. This high degree of specificity of the antibodies allows for a 10,000-fold dilution of pregnancy urine to be assayed directly without interference from other steroids or urinary constituents. Good linear correlation was obtained for urinary-estriol glucuronide equivalents measured in the same subjects by our routine colorimetric method which separates and measures free estriol after hydrolysis. With an accelerated antibody-antigen equilibration of 20 minutes at 40 degrees, 10 samples can be easily processed in less than 90 minutes. The method also allows for the evaluation of variations in the excretion pattern of one estrogen conjugate in normal and high-risk pregnancies."} {"id": "PMID:180809", "title": "The effects of dipivalyl epinephrine on the eye.", "content": "We treated one eye each of ten patients with ocular hypertension with dipivalyl epinephrine (DPE), a congener of epinephrine. Pupil size and intraocular pressure were measured before and at intervals up to 240 minutes after instillation of a single drop of DPE in concentrations from 0.005 to 0.5%. Concentrations of 0.025% DPE and greater significantly reduced IOP, and mydriasis was induced by concentrations of 0.1% DPE or greater. Comcentrations of 0.1% DPE, instilled twice daily for one month, significantly reduced intraocular pressure during diurnal testing on days 2 and 31. No toxic side effects were noted. The DPE produced dose-related increases of cyclic adenosine monophosphate in the aqueous humor of rabbits.", "contents": "The effects of dipivalyl epinephrine on the eye. We treated one eye each of ten patients with ocular hypertension with dipivalyl epinephrine (DPE), a congener of epinephrine. Pupil size and intraocular pressure were measured before and at intervals up to 240 minutes after instillation of a single drop of DPE in concentrations from 0.005 to 0.5%. Concentrations of 0.025% DPE and greater significantly reduced IOP, and mydriasis was induced by concentrations of 0.1% DPE or greater. Comcentrations of 0.1% DPE, instilled twice daily for one month, significantly reduced intraocular pressure during diurnal testing on days 2 and 31. No toxic side effects were noted. The DPE produced dose-related increases of cyclic adenosine monophosphate in the aqueous humor of rabbits."} {"id": "PMID:180810", "title": "The retina in type 5 hyperlipoproteinemia.", "content": "Of two patients with type 5 hyperlipoproteinemia, one exhibited lipemia retinalis with multiple retinal hemorrhages and intraretinal lipid extravasations. Postmortem examination showed hemorrhages in the inner retinal layers and lipid deposits largely in the outer plexiform layer. Lipid within the walls of the retinal vessels was demonstrated by light and electron microscopy. The second patient exhibited visual loss due to progressive obstruction of retinal vessels with white material presumed to be lipid. Findings were confined to one eye.", "contents": "The retina in type 5 hyperlipoproteinemia. Of two patients with type 5 hyperlipoproteinemia, one exhibited lipemia retinalis with multiple retinal hemorrhages and intraretinal lipid extravasations. Postmortem examination showed hemorrhages in the inner retinal layers and lipid deposits largely in the outer plexiform layer. Lipid within the walls of the retinal vessels was demonstrated by light and electron microscopy. The second patient exhibited visual loss due to progressive obstruction of retinal vessels with white material presumed to be lipid. Findings were confined to one eye."} {"id": "PMID:180811", "title": "Atypical retinitis pigmentosa in familial hypobetalipoproteinemia.", "content": "Of three patients with familial hypobetalipoproteinemia, a 42-yeear-old white woman, who was homozygous for this autosomal dominantly inherited disease, had no detectable serum betalipoprotein and had a marked retinal pigmentary degeneration characterized by ring scotomas by Goldmann perimetry, extinguished electroretinographic responses, delayed responses and elevated thresholds during dark adaptometry, and abnoramal cone thresholds. A 4-year-old daughter and a 28-year-old niece of the first patient, who wer heterozygous, had reduced but detectable levels of serum betalipoprotein and no significant retinal pigmentary degeneration. Unlike patients with autosomal recessively inherited abetalipoproteinemia (the Bassen-Kornzweig syndrome), none of our patients had significant neurologic of cardiac defects. Although the level of serum betalipoprotein might be correlated with retinal pigmentary degeneration in familial hypobetalipoproteinemia and abetalipoproteinemia, it appears that neurologic and cardiac defects are dependent on other factors.", "contents": "Atypical retinitis pigmentosa in familial hypobetalipoproteinemia. Of three patients with familial hypobetalipoproteinemia, a 42-yeear-old white woman, who was homozygous for this autosomal dominantly inherited disease, had no detectable serum betalipoprotein and had a marked retinal pigmentary degeneration characterized by ring scotomas by Goldmann perimetry, extinguished electroretinographic responses, delayed responses and elevated thresholds during dark adaptometry, and abnoramal cone thresholds. A 4-year-old daughter and a 28-year-old niece of the first patient, who wer heterozygous, had reduced but detectable levels of serum betalipoprotein and no significant retinal pigmentary degeneration. Unlike patients with autosomal recessively inherited abetalipoproteinemia (the Bassen-Kornzweig syndrome), none of our patients had significant neurologic of cardiac defects. Although the level of serum betalipoprotein might be correlated with retinal pigmentary degeneration in familial hypobetalipoproteinemia and abetalipoproteinemia, it appears that neurologic and cardiac defects are dependent on other factors."} {"id": "PMID:180812", "title": "Spatial summation properties of goldfish ganglion cells.", "content": "At threshold the eye is known to sum quanta as though the total catch were important and not the distribution on the retina. In humans, spatial summation is larger under dark adapted conditions. The extent of this spatial summation is studied in goldfish retinal ganglion cells which are known to receive both rod and cone inputs. The area of summation in single ganglion cells is found to be much larger for rod input compared to cone input. It seems that in single ganglion cells, the spatial summating properties increase markedly in the dark due largely to the neural organization of rod and cone input.", "contents": "Spatial summation properties of goldfish ganglion cells. At threshold the eye is known to sum quanta as though the total catch were important and not the distribution on the retina. In humans, spatial summation is larger under dark adapted conditions. The extent of this spatial summation is studied in goldfish retinal ganglion cells which are known to receive both rod and cone inputs. The area of summation in single ganglion cells is found to be much larger for rod input compared to cone input. It seems that in single ganglion cells, the spatial summating properties increase markedly in the dark due largely to the neural organization of rod and cone input."} {"id": "PMID:180813", "title": "Experimental parturient hypocalcemia in cows following prepartal chemical inhibition of bone resportion.", "content": "Cows fed a balanced diet with the required amounts of calcium and phosphorus developed acute hypocalcemia and hypophosphatemia shortly after parturition, even in the presence of the a responsive parathyroid gland, when bone resorption was selectively inhibited by the prepartal administration of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP). When serum total and ionized calcium levels declined below 6.0 and 1.0 mg/100 ml, respectively, cows developed clinical signs similar to naturally occurring parturient paresis. The plasma immunoreactive parathroid hormone levels were similar prepartum, at parturition, and 1 day postpartum in cows administered EHDP as in control cows. Parathyroid chief cells were predominately in the actively synthesizing phase of the secretory cycle with a prominent Golgi apparatus and lamellar arrays of rough endoplasmic reticulum. Many chief cells were degranulated of mature secretory gransules. Calcitonin activity in thyroid extracts, determined by bioassay, and the numbers of secretory granules in thyroid C-cells were similar in both groups of cows. EDTA infusion after 60 days of the experiment demonstrated that the immediately available calcium reserves were reduced in EHDP-treated cows. The serum calcium remained significantly lower and did not return to preinfusion levels by 24 hours. Serum calcium in control cows returned to within the normal range by 6 hours after EDTA infusion. The urinary excretion of hydroxyproline was consistently reduced prepartum and following EDTA infusion in cows receiving EHDP. The experimental induction of parturient of parturient hypocalcemia by the prepartal administration of EHDP provides a valuable model for studies to investigate the mechanisms in bone responsible for the development of severe hypocalcemia that occurs in response to the increased calcium demand imposed by parturition and the initiation of lactation.", "contents": "Experimental parturient hypocalcemia in cows following prepartal chemical inhibition of bone resportion. Cows fed a balanced diet with the required amounts of calcium and phosphorus developed acute hypocalcemia and hypophosphatemia shortly after parturition, even in the presence of the a responsive parathyroid gland, when bone resorption was selectively inhibited by the prepartal administration of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP). When serum total and ionized calcium levels declined below 6.0 and 1.0 mg/100 ml, respectively, cows developed clinical signs similar to naturally occurring parturient paresis. The plasma immunoreactive parathroid hormone levels were similar prepartum, at parturition, and 1 day postpartum in cows administered EHDP as in control cows. Parathyroid chief cells were predominately in the actively synthesizing phase of the secretory cycle with a prominent Golgi apparatus and lamellar arrays of rough endoplasmic reticulum. Many chief cells were degranulated of mature secretory gransules. Calcitonin activity in thyroid extracts, determined by bioassay, and the numbers of secretory granules in thyroid C-cells were similar in both groups of cows. EDTA infusion after 60 days of the experiment demonstrated that the immediately available calcium reserves were reduced in EHDP-treated cows. The serum calcium remained significantly lower and did not return to preinfusion levels by 24 hours. Serum calcium in control cows returned to within the normal range by 6 hours after EDTA infusion. The urinary excretion of hydroxyproline was consistently reduced prepartum and following EDTA infusion in cows receiving EHDP. The experimental induction of parturient of parturient hypocalcemia by the prepartal administration of EHDP provides a valuable model for studies to investigate the mechanisms in bone responsible for the development of severe hypocalcemia that occurs in response to the increased calcium demand imposed by parturition and the initiation of lactation."} {"id": "PMID:180814", "title": "Motor innervation of the flexor pollicis brevis: an electromyographic study.", "content": "Percutaneous stimulation of the ulnar and median nerves at the wrist, with simultaneous recording of action potentials on a standard electromyograph oscilloscope, was performed to observe the motor innervation of the flexor pollicis brevis muscle. Both the deep and the superficial heads of the muscle were studied in twenty-three subjects. Results showed that the most common pattern of innervation was exclusive ulnar nerve supply in both heads, with 52.4 percent of the subjects showing this pattern. Dual supply by both median and ulnar nerves occurred next in frequency with 19.0 percent showing this pattern in both heads of the muscle. Exclusive median nerve supply was observed in only 9.5 percent of the total cases studied. The remaining 19 percent showed varying patterns, with each head of the muscle supplied differently. If no differentiation between deep and superficial heads is made, this 19 percent may be considered as dual innervation of the muscle. In this case, it may be concluded that 38 percent of the muscles studied showed some type of dual innervation.", "contents": "Motor innervation of the flexor pollicis brevis: an electromyographic study. Percutaneous stimulation of the ulnar and median nerves at the wrist, with simultaneous recording of action potentials on a standard electromyograph oscilloscope, was performed to observe the motor innervation of the flexor pollicis brevis muscle. Both the deep and the superficial heads of the muscle were studied in twenty-three subjects. Results showed that the most common pattern of innervation was exclusive ulnar nerve supply in both heads, with 52.4 percent of the subjects showing this pattern. Dual supply by both median and ulnar nerves occurred next in frequency with 19.0 percent showing this pattern in both heads of the muscle. Exclusive median nerve supply was observed in only 9.5 percent of the total cases studied. The remaining 19 percent showed varying patterns, with each head of the muscle supplied differently. If no differentiation between deep and superficial heads is made, this 19 percent may be considered as dual innervation of the muscle. In this case, it may be concluded that 38 percent of the muscles studied showed some type of dual innervation."} {"id": "PMID:180815", "title": "Effect of prolactin on diluting and concentrating ability in the rat.", "content": "The effect of prolactin on free water clearance (C(H2O)) and reabsorption (T(cH2O)) was assessed in hereditary hypothalamic diabetes insipidus (HHDI) and hydropenic Sprague-Dawley rats. Infusion of ovine prolactin (200 nmol/kg per h) ablated C(H2O) in HHDI rats but had no effect on T(cH2O) in hydropenic rats. Additional experiments in HHDI rats employing submaximal infusions of both ovine and rat prolactin indicated that with increasing infusion rates of these hormones, urine osmolality progressively increased with a maximum effect being reached at 30-40 nmol/kg per h with ovine and 15-20 nmol/kg per h with rat prolactin. In similar experiments, using synthetic lysine-arginine vasopressin, maximum effect on urine osmolality was achieved with an infusion rate of 25-75 pmol/kg per h. During infusion of all three hormones, urinary cyclic AMP excretion increased significantly in a similar fashion. These data suggested that prolactin had a direct effect on collecting tubule permeability and acted through stimulation of cyclic AMP production.", "contents": "Effect of prolactin on diluting and concentrating ability in the rat. The effect of prolactin on free water clearance (C(H2O)) and reabsorption (T(cH2O)) was assessed in hereditary hypothalamic diabetes insipidus (HHDI) and hydropenic Sprague-Dawley rats. Infusion of ovine prolactin (200 nmol/kg per h) ablated C(H2O) in HHDI rats but had no effect on T(cH2O) in hydropenic rats. Additional experiments in HHDI rats employing submaximal infusions of both ovine and rat prolactin indicated that with increasing infusion rates of these hormones, urine osmolality progressively increased with a maximum effect being reached at 30-40 nmol/kg per h with ovine and 15-20 nmol/kg per h with rat prolactin. In similar experiments, using synthetic lysine-arginine vasopressin, maximum effect on urine osmolality was achieved with an infusion rate of 25-75 pmol/kg per h. During infusion of all three hormones, urinary cyclic AMP excretion increased significantly in a similar fashion. These data suggested that prolactin had a direct effect on collecting tubule permeability and acted through stimulation of cyclic AMP production."} {"id": "PMID:180816", "title": "Age-dependent mechanical and biochemical responses to glucagon.", "content": "The age-dependent relationships between glucagon-induced alterations in myocardial mechanics and adenylate cyclase activity in fetal and newborn lambs and adult sheep were evaluated. Glucagon substantially augmented the force of contraction of ventricular myocardium isolated from the adult but not from the fetus or newborn. Similarly, substantial increases in the spontaneous frequency of contraction and tension were observed in adult atrial strips, but not in the fetus or newborn. Comparable activities of phosphodiesterase were observed in extracts from fetal and adult myocardium and were unaltered by the addition of glucagon. Adenylate cyclase activity in adult myocardial homogenate and particulate fractions was comparable to that of fetal tissue. Glucagon stimulation of the particulate fraction produced no change in fetal adenylate cyclase activity whereas a 43% increase in activity was observed in preparations from adult tissue. Sodium fluoride and epinephrine augmented adenylate cyclase activity in both fetal and adult myocardium. Thus, glucagon produced age-dependent, parallel changes in heart rate, active tension development, and particulate fraction adenylate cyclase activity, suggesting that these chronotropic and inotropic responses are indeed mediated by adenylate cyclase and that lack of response in the fetus reflects the absence of mature glucagon receptor sites.", "contents": "Age-dependent mechanical and biochemical responses to glucagon. The age-dependent relationships between glucagon-induced alterations in myocardial mechanics and adenylate cyclase activity in fetal and newborn lambs and adult sheep were evaluated. Glucagon substantially augmented the force of contraction of ventricular myocardium isolated from the adult but not from the fetus or newborn. Similarly, substantial increases in the spontaneous frequency of contraction and tension were observed in adult atrial strips, but not in the fetus or newborn. Comparable activities of phosphodiesterase were observed in extracts from fetal and adult myocardium and were unaltered by the addition of glucagon. Adenylate cyclase activity in adult myocardial homogenate and particulate fractions was comparable to that of fetal tissue. Glucagon stimulation of the particulate fraction produced no change in fetal adenylate cyclase activity whereas a 43% increase in activity was observed in preparations from adult tissue. Sodium fluoride and epinephrine augmented adenylate cyclase activity in both fetal and adult myocardium. Thus, glucagon produced age-dependent, parallel changes in heart rate, active tension development, and particulate fraction adenylate cyclase activity, suggesting that these chronotropic and inotropic responses are indeed mediated by adenylate cyclase and that lack of response in the fetus reflects the absence of mature glucagon receptor sites."} {"id": "PMID:180817", "title": "Pig reticulocytes: I. Transitory glucose permeability and metabolism.", "content": "Glucose permeability and metabolism were examined in the reticulocytes of pigs made anemic by daily administration of phenylhydrazine for 5-7 days. Blood samples containing 70-90% reticulocytes were fractionated according to their density by centrifugation. The most immature reticulocytes obtained from the top centrifugal fractions possessed a glucose permeation mechanism. The salient features of glucose transport include a) saturable kinetics with Vm ranging from 0.1 to 0.4 mumol/ml cell X min and with Km ranging from 6.6 to 12 mM, b) inhibition by phloretin, and c) countertransport characteristics suggesting that the glucose entry was mediated by a mechanism involving membrane carrier-type transport. In the course of reticulocyte maturation leading to mature red cells, the glucose carrier mechanism was discarded or rendered ineffective, resulting in nonglycolytic mature red cells. Glucose and ribose consumptions in the most immature reticulocytes were 2.5 and 0.75 mumol/ml cell X h, respectively. Concomitant with the diminishing glycolytic ability, ribose consumption was enhanced slightly as the reticulocytes matured to red cells. Dihydroxyacetone, a potent metabolic substrate for the mature pig red cell, was utilized readily by the reticulocytes.", "contents": "Pig reticulocytes: I. Transitory glucose permeability and metabolism. Glucose permeability and metabolism were examined in the reticulocytes of pigs made anemic by daily administration of phenylhydrazine for 5-7 days. Blood samples containing 70-90% reticulocytes were fractionated according to their density by centrifugation. The most immature reticulocytes obtained from the top centrifugal fractions possessed a glucose permeation mechanism. The salient features of glucose transport include a) saturable kinetics with Vm ranging from 0.1 to 0.4 mumol/ml cell X min and with Km ranging from 6.6 to 12 mM, b) inhibition by phloretin, and c) countertransport characteristics suggesting that the glucose entry was mediated by a mechanism involving membrane carrier-type transport. In the course of reticulocyte maturation leading to mature red cells, the glucose carrier mechanism was discarded or rendered ineffective, resulting in nonglycolytic mature red cells. Glucose and ribose consumptions in the most immature reticulocytes were 2.5 and 0.75 mumol/ml cell X h, respectively. Concomitant with the diminishing glycolytic ability, ribose consumption was enhanced slightly as the reticulocytes matured to red cells. Dihydroxyacetone, a potent metabolic substrate for the mature pig red cell, was utilized readily by the reticulocytes."} {"id": "PMID:180818", "title": "Do dreams have meaning? An empirical inquiry.", "content": "Three judges attempted to sort randomly selected dreams of normal college students and schizophrenic patients according to dreamer, night of occurrence, and sequential order within a night. Sorting was successful at statistically significant levels (which differed for the two groups) for all but the third task. The authors conclude that dreams are, as depth psychologists have assumed, orderly nonrandom events and that they reflect day-to-day changes in the life of an individual. They note that further work is needed to determine whether there is order among dreams of a given night.", "contents": "Do dreams have meaning? An empirical inquiry. Three judges attempted to sort randomly selected dreams of normal college students and schizophrenic patients according to dreamer, night of occurrence, and sequential order within a night. Sorting was successful at statistically significant levels (which differed for the two groups) for all but the third task. The authors conclude that dreams are, as depth psychologists have assumed, orderly nonrandom events and that they reflect day-to-day changes in the life of an individual. They note that further work is needed to determine whether there is order among dreams of a given night."} {"id": "PMID:180820", "title": "Computed tomograpy and neuroradiology: a fortunate primary union.", "content": "Computed tomography (CT) has led to extensive reassessment of and alterations in the practices of neuroscientists. Many of these alterations and their implications are described. The progress and problems encountered in the past 36 months are reported as well as the trends of future investigations. The principles evolving should apply in many situations as the benefits of CT are extended to other portions of the body.", "contents": "Computed tomograpy and neuroradiology: a fortunate primary union. Computed tomography (CT) has led to extensive reassessment of and alterations in the practices of neuroscientists. Many of these alterations and their implications are described. The progress and problems encountered in the past 36 months are reported as well as the trends of future investigations. The principles evolving should apply in many situations as the benefits of CT are extended to other portions of the body."} {"id": "PMID:180821", "title": "The effects of biological motion on CT resolution.", "content": "A variety of periodic and aperiodic psyiologic motions affect the quality of CT images. This study was initiated to estimate what an optimal scan period should be in the design of CT units. Ultrashort scan periods were experimentally similated in the heart and liver to approximate the parameters of future technology.", "contents": "The effects of biological motion on CT resolution. A variety of periodic and aperiodic psyiologic motions affect the quality of CT images. This study was initiated to estimate what an optimal scan period should be in the design of CT units. Ultrashort scan periods were experimentally similated in the heart and liver to approximate the parameters of future technology."} {"id": "PMID:180822", "title": "Some limitations of computed tomography in the diagnosis of neurological diseases.", "content": "Some of the limitations of CT in the diagnosis of neurologic disease are reported. Problem areas include small lesions; lesions obscured by adjoining structures; small vascular structures and detail of large vessels; cases in which the diagnosis is made but information is incomplete for treatment; cases of incorrect diagnosis; non-nenoplastic lesions mistaken for neoplasms; some subdural hematomas; occasional false negative findings; and misinterpretation due to technical errors. Knowledge and use of the clinical presentation, the performance of other complementary diagnostic procedures, repeat CT scans tailored to the region of interest, and repeat serial scans may assist in reaching the proper diagnosis and diminishing potential error.", "contents": "Some limitations of computed tomography in the diagnosis of neurological diseases. Some of the limitations of CT in the diagnosis of neurologic disease are reported. Problem areas include small lesions; lesions obscured by adjoining structures; small vascular structures and detail of large vessels; cases in which the diagnosis is made but information is incomplete for treatment; cases of incorrect diagnosis; non-nenoplastic lesions mistaken for neoplasms; some subdural hematomas; occasional false negative findings; and misinterpretation due to technical errors. Knowledge and use of the clinical presentation, the performance of other complementary diagnostic procedures, repeat CT scans tailored to the region of interest, and repeat serial scans may assist in reaching the proper diagnosis and diminishing potential error."} {"id": "PMID:180823", "title": "Trends in the development of reconstruction tomography in neuroradiology.", "content": "Because of the new uses of CT, it is difficult to accurately forecast the future balance between it and conventional radiologic techniques. However, the relatively low frequency resolution of CT makes it unlikely that conventional radiology will be completely replaced. Photon noise and the iodine concentration of the contrast medium limit the size of the cerebral vessels which can be studied by CT. Thus angiography is likely to remain the method of choice for fine-detail study of these vessels. For optimal measurements and comparative studies, improved head fixation is required. Given precisely reporducible positioning, stereotaxic surgery and radiation therapy become a reality.", "contents": "Trends in the development of reconstruction tomography in neuroradiology. Because of the new uses of CT, it is difficult to accurately forecast the future balance between it and conventional radiologic techniques. However, the relatively low frequency resolution of CT makes it unlikely that conventional radiology will be completely replaced. Photon noise and the iodine concentration of the contrast medium limit the size of the cerebral vessels which can be studied by CT. Thus angiography is likely to remain the method of choice for fine-detail study of these vessels. For optimal measurements and comparative studies, improved head fixation is required. Given precisely reporducible positioning, stereotaxic surgery and radiation therapy become a reality."} {"id": "PMID:180824", "title": "Computed tomography in infants and children: intracranial neoplasms.", "content": "Cranial CT proved exceptionally accurate in detecting and localizing cerebral neoplasms in children, with only one false negative case in 40 tumors. CT had its greatest diagnostic value in cerebral and cerebellar hemispheric lesions, tuberous sclerosis, and as a screening device for craniopharyngiomas. While CT may provide a definitive diagnosis, additional information form other neuroradiologic studies is often necessary.", "contents": "Computed tomography in infants and children: intracranial neoplasms. Cranial CT proved exceptionally accurate in detecting and localizing cerebral neoplasms in children, with only one false negative case in 40 tumors. CT had its greatest diagnostic value in cerebral and cerebellar hemispheric lesions, tuberous sclerosis, and as a screening device for craniopharyngiomas. While CT may provide a definitive diagnosis, additional information form other neuroradiologic studies is often necessary."} {"id": "PMID:180825", "title": "Computed tomography; the anatomic basis of the zone of diminished density surrounding meningiomas.", "content": "Computed tomography of meningiomas often demonstrates a zone of diminished density surrounding the actual tumor. This zone may be related to widening of the subarachnoid space, cerebral edema, tissue necrosis, or demyelination. A case is presented in which the anatomic basis of the zone of diminished density was shown on pneumoencephalography and at surgery to be an enlarged subarachnoid space.", "contents": "Computed tomography; the anatomic basis of the zone of diminished density surrounding meningiomas. Computed tomography of meningiomas often demonstrates a zone of diminished density surrounding the actual tumor. This zone may be related to widening of the subarachnoid space, cerebral edema, tissue necrosis, or demyelination. A case is presented in which the anatomic basis of the zone of diminished density was shown on pneumoencephalography and at surgery to be an enlarged subarachnoid space."} {"id": "PMID:180826", "title": "Computed tomographic evaluation of hemorrhage secondary to intracranial aneurysm.", "content": "Angiography in patients with subarachnoid hemorrhage secondary to aneurysm gives precise information on the location and size of the aneurysm and the aneurysm and the presence of spasm but gives incomplete information on ventricular size, size and location of hematoma, and extent of infarction. CT demonstrates precisely brain or intraventricular hematoma and, at times, subarachnoid hemorrhage, indicates the extent of infarction; and rapidly documents the degree of hydrocephalus. Infarction secondary to spasm, hematoma, and hydrocephalus are readily differentiated. The CT examination may be repeated as often as necessary without patient discomfort or morbidity. Serial scans allow rapid assessment of change in ventricular size, development and persistence of infarction, and change in size of hematoma.", "contents": "Computed tomographic evaluation of hemorrhage secondary to intracranial aneurysm. Angiography in patients with subarachnoid hemorrhage secondary to aneurysm gives precise information on the location and size of the aneurysm and the aneurysm and the presence of spasm but gives incomplete information on ventricular size, size and location of hematoma, and extent of infarction. CT demonstrates precisely brain or intraventricular hematoma and, at times, subarachnoid hemorrhage, indicates the extent of infarction; and rapidly documents the degree of hydrocephalus. Infarction secondary to spasm, hematoma, and hydrocephalus are readily differentiated. The CT examination may be repeated as often as necessary without patient discomfort or morbidity. Serial scans allow rapid assessment of change in ventricular size, development and persistence of infarction, and change in size of hematoma."} {"id": "PMID:180827", "title": "Demonstration of purulent bacterial intracranial infections by computed tomography.", "content": "Computed tomography is shown to be an important modality in both diagnosis and management of cerebral infections. Representative findings from CT scans of patients with purulent bacterial infection of the meninges, cerebrum, ventricles, and adjacent structures are presented. Material is taken from 2,645 CT scans done in a 1 year period at the Hospital of the University of Pennsylvania. It is hoped that the use of CT will lead to a decrease of morbidity and mortality in entities such as brain abscess and subdural empyema.", "contents": "Demonstration of purulent bacterial intracranial infections by computed tomography. Computed tomography is shown to be an important modality in both diagnosis and management of cerebral infections. Representative findings from CT scans of patients with purulent bacterial infection of the meninges, cerebrum, ventricles, and adjacent structures are presented. Material is taken from 2,645 CT scans done in a 1 year period at the Hospital of the University of Pennsylvania. It is hoped that the use of CT will lead to a decrease of morbidity and mortality in entities such as brain abscess and subdural empyema."} {"id": "PMID:180828", "title": "Stereotaxic computed tomography.", "content": "A method for stereotaxic computed tomography is described. A head fixation system has been devised enabling the exact transfer of information fromthe diagnostic coordinate system of the scanner to other therapeutic or diagnostic coordinate systems.", "contents": "Stereotaxic computed tomography. A method for stereotaxic computed tomography is described. A head fixation system has been devised enabling the exact transfer of information fromthe diagnostic coordinate system of the scanner to other therapeutic or diagnostic coordinate systems."} {"id": "PMID:180829", "title": "Picture processing in computed tomography.", "content": "Using the EMI scanner system computer, picture processing of various kinds can be performed. Computer programs enabling analysis of regions of interest, subtraction, smoothing, and reconstruction in three dimensions have been designed; they are easy enough to be handled by the regular staff. The potential of the methods is illustrated.", "contents": "Picture processing in computed tomography. Using the EMI scanner system computer, picture processing of various kinds can be performed. Computer programs enabling analysis of regions of interest, subtraction, smoothing, and reconstruction in three dimensions have been designed; they are easy enough to be handled by the regular staff. The potential of the methods is illustrated."} {"id": "PMID:180830", "title": "Computed tomography and radionuclide studies in the diagnosis of intracranial disease.", "content": "The accuracy of CT and radionuclide studiies in the diagnosis of intracranial disease is analyzed based on experience in 641 patients. Results indicate that both modalities give reasonably similar precision and that a modest improvement in diagnosis can be expected if both techniques are employed. It is emphasized that the radionuclide studies used routinely included what are rightfully considered adjunctive scanning procedures, so that results must be considered in this light.", "contents": "Computed tomography and radionuclide studies in the diagnosis of intracranial disease. The accuracy of CT and radionuclide studiies in the diagnosis of intracranial disease is analyzed based on experience in 641 patients. Results indicate that both modalities give reasonably similar precision and that a modest improvement in diagnosis can be expected if both techniques are employed. It is emphasized that the radionuclide studies used routinely included what are rightfully considered adjunctive scanning procedures, so that results must be considered in this light."} {"id": "PMID:180831", "title": "High resolution computed tomography of the orbit withthe Ohio Nuclear Delta head scanner.", "content": "The orbit is an ideal structure to examine by CT because of large differences between absorption values of retroorbital fat and other structures such as muscle, optic nerve, and ophthalmic artery. Spatial resolution in CT is dependent upon the volume of each pixel (individual picture element). Whereas the pixel volume of the original EMI scanner was 117 mm, that of the Ohio Nuclear Delta head scanner employed in this paper is only 5 mm. Ovver 200 patients have been examined using this scanning instrument, including 32 patients in whom the orbits were specifically examined with a scan plane parallel to Reid's baseline. Representative abnormalities are discussed and illustrated. Orbital tumors such as hemangiomas, lymphomas, meningiomas, and inflammatory pseudotumors can be accurately localized while still very small.", "contents": "High resolution computed tomography of the orbit withthe Ohio Nuclear Delta head scanner. The orbit is an ideal structure to examine by CT because of large differences between absorption values of retroorbital fat and other structures such as muscle, optic nerve, and ophthalmic artery. Spatial resolution in CT is dependent upon the volume of each pixel (individual picture element). Whereas the pixel volume of the original EMI scanner was 117 mm, that of the Ohio Nuclear Delta head scanner employed in this paper is only 5 mm. Ovver 200 patients have been examined using this scanning instrument, including 32 patients in whom the orbits were specifically examined with a scan plane parallel to Reid's baseline. Representative abnormalities are discussed and illustrated. Orbital tumors such as hemangiomas, lymphomas, meningiomas, and inflammatory pseudotumors can be accurately localized while still very small."} {"id": "PMID:180832", "title": "Further progress in CT scanning and computerized radiation therapy treatment planning.", "content": "Total body computed tomography has introduced a unique method of obtaining body contours as well as anatomical representations for radiation therapy treatment planning. CT scanning combined with computerized radiation therapy treatment planning has improved accuracy and contributed greatly to the solution of complex treatment problems. CT scans can also be used to evaluate the progress of patients undergoing radiation therapy.", "contents": "Further progress in CT scanning and computerized radiation therapy treatment planning. Total body computed tomography has introduced a unique method of obtaining body contours as well as anatomical representations for radiation therapy treatment planning. CT scanning combined with computerized radiation therapy treatment planning has improved accuracy and contributed greatly to the solution of complex treatment problems. CT scans can also be used to evaluate the progress of patients undergoing radiation therapy."} {"id": "PMID:180833", "title": "Health planning for computed tomography: perspectives and problems.", "content": "Computed tomography has been introduced to the health care system at a time when health care planning is still evolving. Unlike the recent past, final authorization of large expenditures and new services such as CT now lies outside the providers of care and is based on laws and regulations that are not familiar to many physicians. A brief review of the principal federal statutes is presented from the Hill-Burton Act to the National Health Planning and Resources Development Act of 1974. Recognizing the unique problems in certain special service areas such as CT, the state of Indiana has formed committees to collect information and develop recommendations to assist its health planners in their actions and decisions under the federal statutes. The quantitative problems which the Indiana CT committee must address are presented in some detail, problems that other health planners face as well.", "contents": "Health planning for computed tomography: perspectives and problems. Computed tomography has been introduced to the health care system at a time when health care planning is still evolving. Unlike the recent past, final authorization of large expenditures and new services such as CT now lies outside the providers of care and is based on laws and regulations that are not familiar to many physicians. A brief review of the principal federal statutes is presented from the Hill-Burton Act to the National Health Planning and Resources Development Act of 1974. Recognizing the unique problems in certain special service areas such as CT, the state of Indiana has formed committees to collect information and develop recommendations to assist its health planners in their actions and decisions under the federal statutes. The quantitative problems which the Indiana CT committee must address are presented in some detail, problems that other health planners face as well."} {"id": "PMID:180834", "title": "Economic analysis of computed tomography units.", "content": "All operating CT installations in the United States were surveyed in January 1976; data were obtained from 98 of 140 installations. Although the respondents represented 80 head units and 18 head and body units, the overwhelming experience was with head CT studies. CT equipment was installed in an average of 1.3 months, operated 64 hr per week and examined 50-55 patients per week. A downtime of 7 hr per week was reported. Radiologists are responsible for 92 of 98 installations, and 90% of installations are in a hospital. The scheduling delay averages 1.6 days for inpatients and 11.5 days for outpatients. The delay is increasing in many installations. The estimated total yearly technical cost is +325,000-+371,000 per installation, depending upon patient volume. The estimated technical cost per patient (when 50 patients per week are studied) compares favorably with the estimated net revenue per patient from the average basic technical charge (+130 compared to +138). A separate billing method is used by 59% of installations, and 76% have an extra charge for contrast injection and additional studies; 60% of patients receive contrast. The reported total charges during the last 3 months were higher in installations that (1) charged additionally for contrast, (2) were located in outpatient settings, and (3) had nonradiologists as the responsible physician. It should be emphasized that most CT installations are not independent activities and should be considered an integral part of a diagnostic radiology department or office.", "contents": "Economic analysis of computed tomography units. All operating CT installations in the United States were surveyed in January 1976; data were obtained from 98 of 140 installations. Although the respondents represented 80 head units and 18 head and body units, the overwhelming experience was with head CT studies. CT equipment was installed in an average of 1.3 months, operated 64 hr per week and examined 50-55 patients per week. A downtime of 7 hr per week was reported. Radiologists are responsible for 92 of 98 installations, and 90% of installations are in a hospital. The scheduling delay averages 1.6 days for inpatients and 11.5 days for outpatients. The delay is increasing in many installations. The estimated total yearly technical cost is +325,000-+371,000 per installation, depending upon patient volume. The estimated technical cost per patient (when 50 patients per week are studied) compares favorably with the estimated net revenue per patient from the average basic technical charge (+130 compared to +138). A separate billing method is used by 59% of installations, and 76% have an extra charge for contrast injection and additional studies; 60% of patients receive contrast. The reported total charges during the last 3 months were higher in installations that (1) charged additionally for contrast, (2) were located in outpatient settings, and (3) had nonradiologists as the responsible physician. It should be emphasized that most CT installations are not independent activities and should be considered an integral part of a diagnostic radiology department or office."} {"id": "PMID:180837", "title": "Computed tomography of the body: initial clinical trial with the EMI prototype.", "content": "A review of the first 400 cases examined on one of three prototype EMI body scanners is presented. During the initial evaluation phases, it became obvious that computed tomography of the body has tremendous potential in the evaluation of various organs and disease states. The technique has been most useful in evaluating patients with known or suspected abdominal neoplasm, particularly lesions of liver, pancreas, retroperitoneum, and kidney. Too few cases have been studied to realistically quantitate its impact on the total field of medical diagnostic imaging.", "contents": "Computed tomography of the body: initial clinical trial with the EMI prototype. A review of the first 400 cases examined on one of three prototype EMI body scanners is presented. During the initial evaluation phases, it became obvious that computed tomography of the body has tremendous potential in the evaluation of various organs and disease states. The technique has been most useful in evaluating patients with known or suspected abdominal neoplasm, particularly lesions of liver, pancreas, retroperitoneum, and kidney. Too few cases have been studied to realistically quantitate its impact on the total field of medical diagnostic imaging."} {"id": "PMID:180838", "title": "Picture quality of computed tomography.", "content": "Some limitations that impair the picture quality of computed tomography are presented. Picture grain is analyzed in detail and its relationship to different matrix sizes is demonstrated. The choices of matrix size for viewing various parts of the body are defined, and the need for higher resolution in the future is debated. Comparison is made between two scanning systems: the moving fan beam with rotation and the simple rotating fan beam. Possible artifacts in the picture caused by drift and delay in dector response are discussed.", "contents": "Picture quality of computed tomography. Some limitations that impair the picture quality of computed tomography are presented. Picture grain is analyzed in detail and its relationship to different matrix sizes is demonstrated. The choices of matrix size for viewing various parts of the body are defined, and the need for higher resolution in the future is debated. Comparison is made between two scanning systems: the moving fan beam with rotation and the simple rotating fan beam. Possible artifacts in the picture caused by drift and delay in dector response are discussed."} {"id": "PMID:180839", "title": "Computed tomography of the body: early trends in application and accuracy of the method.", "content": "Early experience with extracranial CT has shown this diagnostic method to be highly accurate in evaluating the liver, pancreas, kidneys, retroperitoneum, and pelvis. The diagnosis of neoplasm, inflammatory changes, and normal moophologic variants is possible. Initial data indicat that this modality may assume a primary role in the evaluation of the liver, pancreas, and retroperitoneum (e.g., the differentiation of medical from surgical jaundice and the distinction of solid from cystic lesions). In the thorax, the results appear far less dramatic. CT scans rarely surpass the diagnostic accuracy of conventional radiologic studies. Initial results indicate a need for studies comparing CT with radionuclide examinations, ultrasonography, and other conventional radiographic procedures as well as for evaluating its use in radiation therapy planning and follow-up.", "contents": "Computed tomography of the body: early trends in application and accuracy of the method. Early experience with extracranial CT has shown this diagnostic method to be highly accurate in evaluating the liver, pancreas, kidneys, retroperitoneum, and pelvis. The diagnosis of neoplasm, inflammatory changes, and normal moophologic variants is possible. Initial data indicat that this modality may assume a primary role in the evaluation of the liver, pancreas, and retroperitoneum (e.g., the differentiation of medical from surgical jaundice and the distinction of solid from cystic lesions). In the thorax, the results appear far less dramatic. CT scans rarely surpass the diagnostic accuracy of conventional radiologic studies. Initial results indicate a need for studies comparing CT with radionuclide examinations, ultrasonography, and other conventional radiographic procedures as well as for evaluating its use in radiation therapy planning and follow-up."} {"id": "PMID:180840", "title": "Computed tomography of the liver.", "content": "This work examines the scope and accuracy of CT in the detection of tumors, abscesses, cysts, and parenchymal disorders of the liver. While CT remains an emerging modality, it is shown to be equal to nuclear medicine in detecting mass lesions. It has also been possible to distinguish obstructive from nonobstructive jaundice. Presently, CT is not well suited to the study of cirrhosis. Technological advances in CT design and contrast agents offer promise of significantly improved resolution.", "contents": "Computed tomography of the liver. This work examines the scope and accuracy of CT in the detection of tumors, abscesses, cysts, and parenchymal disorders of the liver. While CT remains an emerging modality, it is shown to be equal to nuclear medicine in detecting mass lesions. It has also been possible to distinguish obstructive from nonobstructive jaundice. Presently, CT is not well suited to the study of cirrhosis. Technological advances in CT design and contrast agents offer promise of significantly improved resolution."} {"id": "PMID:180841", "title": "Computed tomographic evaluation of aortic aneurysms.", "content": "Applications of computed tomography are being extended from the brain to other body parts. This report describes CT scanning of abdominal and thoracic aortic aneurysms in 30 patients. CT shows greatest promise in abdominal aortic scanning, where reliable identification of the aorta can be achieved even in the absence of enlargement or calcification. However, current limitations prevent visualization of internal detail such as intimal plaques or mural thrombi. Technical advances are described which should have an important bearing on this.", "contents": "Computed tomographic evaluation of aortic aneurysms. Applications of computed tomography are being extended from the brain to other body parts. This report describes CT scanning of abdominal and thoracic aortic aneurysms in 30 patients. CT shows greatest promise in abdominal aortic scanning, where reliable identification of the aorta can be achieved even in the absence of enlargement or calcification. However, current limitations prevent visualization of internal detail such as intimal plaques or mural thrombi. Technical advances are described which should have an important bearing on this."} {"id": "PMID:180842", "title": "Computed tomography of the heart.", "content": "In an attempt to evaluate the possible usefulness of transmission computed tomography, CT scans of the chest of a series of dead dogs were obtained by means of an EMI body scanner. The sections thus obtained with and without the injection of contrast material reveal a great deal of cardiac morphology. Infarcts of the heart produced prior to scanning were imaged as regions of lower x-ray attenuation. The hearts of a series of live dogs following infarction were imaged by means of a positron emission transverse tomomograph (PETT) following administration of C-palmitate. The images permitted assessment of the relative size of the infarct. The relative advantages of transmission and emission tomography in cardiac visualization are discussed.", "contents": "Computed tomography of the heart. In an attempt to evaluate the possible usefulness of transmission computed tomography, CT scans of the chest of a series of dead dogs were obtained by means of an EMI body scanner. The sections thus obtained with and without the injection of contrast material reveal a great deal of cardiac morphology. Infarcts of the heart produced prior to scanning were imaged as regions of lower x-ray attenuation. The hearts of a series of live dogs following infarction were imaged by means of a positron emission transverse tomomograph (PETT) following administration of C-palmitate. The images permitted assessment of the relative size of the infarct. The relative advantages of transmission and emission tomography in cardiac visualization are discussed."} {"id": "PMID:180843", "title": "Cardiac reconstruction imaging in relation to other ultrasound systems and computed tomography.", "content": "A computer-controlled system is described for the generation of two-dimensional motion images of the heart. A standard B scanner is used to scan the area of interest during 40-50 cardiac cycles, and the computer controls recording of the ultrasound signals, beam position indicators, and physiologic data. The ultrasonic echoes are reformatted by the computer into sequential frames by reference to the ECG. Images are displayed in motion on a large monitor, and hard copy is obtained on 35 mm cine film. Off-line computer-controlled signal processing is utilized for image enhancement of clinical studies. Real-time systems for the production of two-dimensional motion images of the heart are discussed and compared to computer reconstruction of ultrasound cardiac imaging. The advantages of ultrasound imaging of the heart and other body areas are presented, and prospectives are offered by which the present and future roles of ultrasound can be evaluated in respect and future roles of ultrasound can be evaluated in respect to computed tomography. It is concluded that ultrasound will remain the primary noninvasive modality for cardiac motion study and that ultrasound will continue to provide important clinical information in all parts of the body where it is currently employed.", "contents": "Cardiac reconstruction imaging in relation to other ultrasound systems and computed tomography. A computer-controlled system is described for the generation of two-dimensional motion images of the heart. A standard B scanner is used to scan the area of interest during 40-50 cardiac cycles, and the computer controls recording of the ultrasound signals, beam position indicators, and physiologic data. The ultrasonic echoes are reformatted by the computer into sequential frames by reference to the ECG. Images are displayed in motion on a large monitor, and hard copy is obtained on 35 mm cine film. Off-line computer-controlled signal processing is utilized for image enhancement of clinical studies. Real-time systems for the production of two-dimensional motion images of the heart are discussed and compared to computer reconstruction of ultrasound cardiac imaging. The advantages of ultrasound imaging of the heart and other body areas are presented, and prospectives are offered by which the present and future roles of ultrasound can be evaluated in respect and future roles of ultrasound can be evaluated in respect to computed tomography. It is concluded that ultrasound will remain the primary noninvasive modality for cardiac motion study and that ultrasound will continue to provide important clinical information in all parts of the body where it is currently employed."} {"id": "PMID:180844", "title": "Clinical and serologic responses of volunteers infected with phlebotomus fever virus (Sicilian type).", "content": "Twenty volunteers were inoculated with various doses of human serum containing Phlebotomus fever virus (Sicilian type) to determine their clinical and serologic responses as well as the human infectious dose50 of the virus. All infected subjects developed fever which varied in duration from 6 to 74 hours. The most common symptoms during sandfly fever were headache, anorexia, myalgia, photophobia, low back and retro-orbital pain. Infected individuals developed a marked leukopenia characterized by an initial lymphopenia followed by protracted neutropenia. Little complement fixing antibody was detected in convalescent sera but most subjects developed significant rises in hemagglutination inhibiting antibodies. All infected subjects developed specific neutralizing antibodies with titers ranging from 1:40 to 1:2,560. Of the three serologic tests performed, the plaque reduction neutralization method appears to be the most sensitive test for detecting antibodies to Phlebotomus fever viruses.", "contents": "Clinical and serologic responses of volunteers infected with phlebotomus fever virus (Sicilian type). Twenty volunteers were inoculated with various doses of human serum containing Phlebotomus fever virus (Sicilian type) to determine their clinical and serologic responses as well as the human infectious dose50 of the virus. All infected subjects developed fever which varied in duration from 6 to 74 hours. The most common symptoms during sandfly fever were headache, anorexia, myalgia, photophobia, low back and retro-orbital pain. Infected individuals developed a marked leukopenia characterized by an initial lymphopenia followed by protracted neutropenia. Little complement fixing antibody was detected in convalescent sera but most subjects developed significant rises in hemagglutination inhibiting antibodies. All infected subjects developed specific neutralizing antibodies with titers ranging from 1:40 to 1:2,560. Of the three serologic tests performed, the plaque reduction neutralization method appears to be the most sensitive test for detecting antibodies to Phlebotomus fever viruses."} {"id": "PMID:180845", "title": "Japanese encephalitis virus in Northern Taiwan, 1969-1973.", "content": "Sentinel pigs were bled and mosiquitoes were collected for isolation of Japanese encephalitis virus (JEV) between 1969 and 1973 in a rural area of northern Taiwan which reported a high annual incidence of human cases. The study site included a farmyard, schools, a bat cave, rice paddies and a heronry. Although Culex annulus was collected in every month of the year, isolations were made only in midsummer and only from Culex annulus and (once) from Culex tritaeniorhynchus. These isolates were usually collected from pig-related sources. Human cases in the vicinity of the study site were reported 3 to 6 weeks following the initial isolations from sentinel pigs. Isolations were made only for 4 to 8 weeks each summer. The isolation of JEV was not related to the availability of susceptible pigs or the spring or summer peaks in prevalence of Culex annulus. Despite periodic draining of rice paddies and the application of insecticides, sufficient numbers of Culex annulus were available to support transmission of JEV in each year of the study.", "contents": "Japanese encephalitis virus in Northern Taiwan, 1969-1973. Sentinel pigs were bled and mosiquitoes were collected for isolation of Japanese encephalitis virus (JEV) between 1969 and 1973 in a rural area of northern Taiwan which reported a high annual incidence of human cases. The study site included a farmyard, schools, a bat cave, rice paddies and a heronry. Although Culex annulus was collected in every month of the year, isolations were made only in midsummer and only from Culex annulus and (once) from Culex tritaeniorhynchus. These isolates were usually collected from pig-related sources. Human cases in the vicinity of the study site were reported 3 to 6 weeks following the initial isolations from sentinel pigs. Isolations were made only for 4 to 8 weeks each summer. The isolation of JEV was not related to the availability of susceptible pigs or the spring or summer peaks in prevalence of Culex annulus. Despite periodic draining of rice paddies and the application of insecticides, sufficient numbers of Culex annulus were available to support transmission of JEV in each year of the study."} {"id": "PMID:180846", "title": "Isolation of Langat virus from Haemaphysalis papuana Thorell in Thailand.", "content": "A strain of Langat virus (LGT), T-1674, was isolated from a pool of Haemaphysalis papuana Thorell collected in the forest of Khao Yai National Park in Central Thailand. The isolated virus was found to have growth and antigenic similarity to the prototype Langat strain (TP-21). This is the first report of a natural infection of Haemaphysalis ticks with LGT and of the isolation of this arbovirus in Thailand. The wide distribution of known vectors of LGT in Thailand suggests that the virus may be present in other areas of the country.", "contents": "Isolation of Langat virus from Haemaphysalis papuana Thorell in Thailand. A strain of Langat virus (LGT), T-1674, was isolated from a pool of Haemaphysalis papuana Thorell collected in the forest of Khao Yai National Park in Central Thailand. The isolated virus was found to have growth and antigenic similarity to the prototype Langat strain (TP-21). This is the first report of a natural infection of Haemaphysalis ticks with LGT and of the isolation of this arbovirus in Thailand. The wide distribution of known vectors of LGT in Thailand suggests that the virus may be present in other areas of the country."} {"id": "PMID:180847", "title": "Collagenolysis of rat tail tendons by crude corneal collagenase and clostridiopeptidase A.", "content": "An experimental apparatus, which uses freshly collected, nondenatured rat tail tendons as substrate against crude corneal collagenase from alkali-burned rabbit corneas and clostridiopeptidase A, is introduced. The apparatus makes it possible to compare the collagenolytic activity of the two enzymes directly on intact connective tissue similar to intact corneal tissue. It was found that the two enzymes were able to reduce the tensile strength of rat tail tendons to less than 100 g in less than 5 h. The two enzymes attacked the tendons in structurally the same manner, estimated from a statistical model. The conclusion drawn is that crude corneal collagenase can degradate intact connective tissue indicating that it can attack the intact cornea.", "contents": "Collagenolysis of rat tail tendons by crude corneal collagenase and clostridiopeptidase A. An experimental apparatus, which uses freshly collected, nondenatured rat tail tendons as substrate against crude corneal collagenase from alkali-burned rabbit corneas and clostridiopeptidase A, is introduced. The apparatus makes it possible to compare the collagenolytic activity of the two enzymes directly on intact connective tissue similar to intact corneal tissue. It was found that the two enzymes were able to reduce the tensile strength of rat tail tendons to less than 100 g in less than 5 h. The two enzymes attacked the tendons in structurally the same manner, estimated from a statistical model. The conclusion drawn is that crude corneal collagenase can degradate intact connective tissue indicating that it can attack the intact cornea."} {"id": "PMID:180852", "title": "Cyclophosphamide-induced amelioration of Marek's disease in Marek's disease-susceptible chickens.", "content": "Bursa- and thymus-dependent functions were examined in Marek's disease (MD)-susceptible normal chickens and in chickens treated with 5 and 16 mg of cyclophosphamide (CY) at the time of hatching. Chickens not exposed to Marek's disease virus (MDV) and treated with CY temporarily lost mitogenic response to concanavalin A but regained full response after 5 weeks. Bursa-dependent functions, such as presence of germinal centers in spleen and cecal tonsils, morphologic features of bursa, and sheep red blood cell antibody response were completely lost in chickens treated with 16 mg of CY and only partly retained in chickens treated with 5 mg of CY. In chickens exposed to MDV, the degree of thymus-dependent spleen cell mitogenic response was directly related to frequency and severity of MD. Chickens treated with 16 mg of CY had a mild mitogenic depression and low frequency and severity of MD lesions, whereas those treated with 5 mg of CY and those not treated had marked mitogenic depression and high frequency and severity of MD. Suppressions of bursa- and thymus-dependent functions by MDV alone were also evident when comparing MDV-exposed and nonexposed chickens. The results also indicate that presence of small, residual amounts of humoral factor(s) may enhance MDV oncogenesis.", "contents": "Cyclophosphamide-induced amelioration of Marek's disease in Marek's disease-susceptible chickens. Bursa- and thymus-dependent functions were examined in Marek's disease (MD)-susceptible normal chickens and in chickens treated with 5 and 16 mg of cyclophosphamide (CY) at the time of hatching. Chickens not exposed to Marek's disease virus (MDV) and treated with CY temporarily lost mitogenic response to concanavalin A but regained full response after 5 weeks. Bursa-dependent functions, such as presence of germinal centers in spleen and cecal tonsils, morphologic features of bursa, and sheep red blood cell antibody response were completely lost in chickens treated with 16 mg of CY and only partly retained in chickens treated with 5 mg of CY. In chickens exposed to MDV, the degree of thymus-dependent spleen cell mitogenic response was directly related to frequency and severity of MD. Chickens treated with 16 mg of CY had a mild mitogenic depression and low frequency and severity of MD lesions, whereas those treated with 5 mg of CY and those not treated had marked mitogenic depression and high frequency and severity of MD. Suppressions of bursa- and thymus-dependent functions by MDV alone were also evident when comparing MDV-exposed and nonexposed chickens. The results also indicate that presence of small, residual amounts of humoral factor(s) may enhance MDV oncogenesis."} {"id": "PMID:180853", "title": "Effects of swab materials on infectious bovine rhinotracheitis virus.", "content": "The recovery rates of infectious bovine rhinotracheitis virus from swab materials were compared. The adsorptive and elutive properties of cotton, polyester, and calcium alginate wool were examined by direct exposure of infectious bovine rhinotracheitis virus to swab materials in buffered tissue culture medium. Calcium alginate wool was virucidal; this was apparent after 2 hours' exposure. Cotton and polyester swab materials exhibited little virucidal effects. The addition of wooden applicator sticks with the swab materials reduced viral titers further.", "contents": "Effects of swab materials on infectious bovine rhinotracheitis virus. The recovery rates of infectious bovine rhinotracheitis virus from swab materials were compared. The adsorptive and elutive properties of cotton, polyester, and calcium alginate wool were examined by direct exposure of infectious bovine rhinotracheitis virus to swab materials in buffered tissue culture medium. Calcium alginate wool was virucidal; this was apparent after 2 hours' exposure. Cotton and polyester swab materials exhibited little virucidal effects. The addition of wooden applicator sticks with the swab materials reduced viral titers further."} {"id": "PMID:180854", "title": "Murine cytomegalovirus glomerulonephritis: clinical and ultrastructural observations.", "content": "This investigation was initiated to study and correlate the clinical and ultrastructural aspects of glomerulonephritis induced in the laboratory mouse by the intraperitoneal injection of a sublethal dose of murine cytomegalovirus. An attempt was made to ascertain the pathogenesis of the glomerular changes and the resultant viremia. Murine cytomegalovirus infection caused an acute transient glomerulonephritis in young female mice of the HA/ICR strain. Mice that survived a sublethal inoculation of homogenized infected gland developed transient proteinuria and excreted tubular casts. The murine cytomegalovirus infection resulted in a glomerular lesion that was selective for the mesangial cell. After entering the mesangial cell by phagocytosis the virus replicated in the nucleus and was excreted into the channel of the mesangial matrix, with extension toward the periphery of the capillary loop and adjacent to the urinary space. Virus particles were rarely found in the glomerulus after the 5th day of infection and chronic renal disease was not observed.", "contents": "Murine cytomegalovirus glomerulonephritis: clinical and ultrastructural observations. This investigation was initiated to study and correlate the clinical and ultrastructural aspects of glomerulonephritis induced in the laboratory mouse by the intraperitoneal injection of a sublethal dose of murine cytomegalovirus. An attempt was made to ascertain the pathogenesis of the glomerular changes and the resultant viremia. Murine cytomegalovirus infection caused an acute transient glomerulonephritis in young female mice of the HA/ICR strain. Mice that survived a sublethal inoculation of homogenized infected gland developed transient proteinuria and excreted tubular casts. The murine cytomegalovirus infection resulted in a glomerular lesion that was selective for the mesangial cell. After entering the mesangial cell by phagocytosis the virus replicated in the nucleus and was excreted into the channel of the mesangial matrix, with extension toward the periphery of the capillary loop and adjacent to the urinary space. Virus particles were rarely found in the glomerulus after the 5th day of infection and chronic renal disease was not observed."} {"id": "PMID:180855", "title": "In vitro effects of elastase and collagenase on mechanical properties of hamster lungs.", "content": "A previous study of hamsters, 21 days after intratracheal treatment with pancreatic elastase, showed development of emphysema, shift of the volume-pressure curve up an to the left, with both air and saline filling, and increase in quasistatic lung compliance. There was also a striking increase in vital capacity and lung volume at transpulmonary pressure of 25 cm H2O (TLC25); however, 21 days after collagenase treatment, there was only a slight increase in TLC25. The lung volume changes were not consistent with the theory that the collagen fiber network is responsible for limiting distension of the lung. This report considers saline-filled volume-pressure curves studied in excised hamster lungs after incubation with endotracheally instilled pancreatic elastase or clostridial collagenase solutions. Fluid retained in the lungs after the first infusion-withdrawal cycle was significantly greater in lungs treated with elastase than in lungs treated with collagenase or in control lungs. Total fluid volume at full inflation was similar in the 3 groups. Chord compliance of lungs treated with collagenase was greater at high volume range than that in lungs treated with elastase or control lungs; chord compliance of elastase-treated lungs was higher at mid-volume range than that of collagenase-treated or control lungs. The results of these in vitro studies are consistent with the theory of independently functioning elastic and collagen fiber networks, with the latter limiting lung distensibility at high volumes, and the former providing great extensibility at low volumes. Events that are part of the repair process after elastase injury may result in a change in the orientation of collagen in alveolar tissue and appear to account for the differing effects of in vivo and in vitro elastase treatment on the static mechanical properties of the lungs.", "contents": "In vitro effects of elastase and collagenase on mechanical properties of hamster lungs. A previous study of hamsters, 21 days after intratracheal treatment with pancreatic elastase, showed development of emphysema, shift of the volume-pressure curve up an to the left, with both air and saline filling, and increase in quasistatic lung compliance. There was also a striking increase in vital capacity and lung volume at transpulmonary pressure of 25 cm H2O (TLC25); however, 21 days after collagenase treatment, there was only a slight increase in TLC25. The lung volume changes were not consistent with the theory that the collagen fiber network is responsible for limiting distension of the lung. This report considers saline-filled volume-pressure curves studied in excised hamster lungs after incubation with endotracheally instilled pancreatic elastase or clostridial collagenase solutions. Fluid retained in the lungs after the first infusion-withdrawal cycle was significantly greater in lungs treated with elastase than in lungs treated with collagenase or in control lungs. Total fluid volume at full inflation was similar in the 3 groups. Chord compliance of lungs treated with collagenase was greater at high volume range than that in lungs treated with elastase or control lungs; chord compliance of elastase-treated lungs was higher at mid-volume range than that of collagenase-treated or control lungs. The results of these in vitro studies are consistent with the theory of independently functioning elastic and collagen fiber networks, with the latter limiting lung distensibility at high volumes, and the former providing great extensibility at low volumes. Events that are part of the repair process after elastase injury may result in a change in the orientation of collagen in alveolar tissue and appear to account for the differing effects of in vivo and in vitro elastase treatment on the static mechanical properties of the lungs."} {"id": "PMID:180856", "title": "Effects of rhinovirus infection of pulmonary function of healthy human volunteers.", "content": "The effects of experimentally induced rhinovirus and mycoplasmal respiratory tract infections on the pulmonary function of healthy, young, adult volunteers were investigated prospectively. Before inoculation, 12 volunteers were completely normal, whereas 9 had increased frequency dependence of compliance as their only abnormality of pulmonary function. Rhinovirus infection was induced in 8 of the completely normal volunteers, and 5 developed increased frequency dependence of compliance at the time of illness. These changes returned toward normal during the following 2 weeks and were not associated with concomitant changes in any other parameter of pulmonary function, including \"closing volume\". Three subjects with increased frequency dependence of compliance as their only abnormality before rhinovirus infection developed no significant change in dynamic compliance or any other abnormality in pulmonary function after infection. No changes in pulmonary function were detected in 3 volunteers with experimentally induced mycoplasmal infection. These finding suggest that although rhinovirus infections are associated primarily with upper respiratory illness, they can produce transient peripheral airway abnormalities in previously normal young adults; however, closing volumes, as well as routine pulmonary function studies, may not detect these changes.", "contents": "Effects of rhinovirus infection of pulmonary function of healthy human volunteers. The effects of experimentally induced rhinovirus and mycoplasmal respiratory tract infections on the pulmonary function of healthy, young, adult volunteers were investigated prospectively. Before inoculation, 12 volunteers were completely normal, whereas 9 had increased frequency dependence of compliance as their only abnormality of pulmonary function. Rhinovirus infection was induced in 8 of the completely normal volunteers, and 5 developed increased frequency dependence of compliance at the time of illness. These changes returned toward normal during the following 2 weeks and were not associated with concomitant changes in any other parameter of pulmonary function, including \"closing volume\". Three subjects with increased frequency dependence of compliance as their only abnormality before rhinovirus infection developed no significant change in dynamic compliance or any other abnormality in pulmonary function after infection. No changes in pulmonary function were detected in 3 volunteers with experimentally induced mycoplasmal infection. These finding suggest that although rhinovirus infections are associated primarily with upper respiratory illness, they can produce transient peripheral airway abnormalities in previously normal young adults; however, closing volumes, as well as routine pulmonary function studies, may not detect these changes."} {"id": "PMID:180860", "title": "Recovery from rabies in man.", "content": "A 45-year-old woman from Mendoza, Argentina, was severely bitten by a dog that died 4 days later. Before death, the dog was nervous, aggressive, and had occasional seizures. Ten days after the woman had been bitten, rabies vaccine treatment was begun: 14 daily doses of suckling mouse brain vaccine followed by 2 booster doses. Twenty-one days after the biting episode, she developed a cerebellar striatal syndrome, which persisted throughout several months, and severe encephalitic symptoms, which persisted for 75 days. After 13 months, recovery was nearly complete. The patient's serum and cerebrospinal fluid contained rabies-neutralizing antibodies reaching maximum titers of 1:640 000 and 1:160 000, respectively. Titers of this magnitude have never been previusly recorded after suckling mouse brain vaccine treatment. This phenomenon, together with the epidemiologic, clinical, and laboratory data presented, supports the conclusion of a nonfatal case of rabies in man.", "contents": "Recovery from rabies in man. A 45-year-old woman from Mendoza, Argentina, was severely bitten by a dog that died 4 days later. Before death, the dog was nervous, aggressive, and had occasional seizures. Ten days after the woman had been bitten, rabies vaccine treatment was begun: 14 daily doses of suckling mouse brain vaccine followed by 2 booster doses. Twenty-one days after the biting episode, she developed a cerebellar striatal syndrome, which persisted throughout several months, and severe encephalitic symptoms, which persisted for 75 days. After 13 months, recovery was nearly complete. The patient's serum and cerebrospinal fluid contained rabies-neutralizing antibodies reaching maximum titers of 1:640 000 and 1:160 000, respectively. Titers of this magnitude have never been previusly recorded after suckling mouse brain vaccine treatment. This phenomenon, together with the epidemiologic, clinical, and laboratory data presented, supports the conclusion of a nonfatal case of rabies in man."} {"id": "PMID:180861", "title": "Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.", "content": "Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.", "contents": "Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors. Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy."} {"id": "PMID:180862", "title": "[Detection and distriburion of slow pre-betalipoprotein in agar gel electrophoresis of total serum in 204 cases of mixed hyperlipidemia].", "content": "The demonstration in certain sera by electrophoresis an Agar gel, according to Noble's technique, of a further band of intermediate pre-betalipoprotein, between the betalipoproteins and the usual rapid pre-betalipoproteins, led to the designation of this fraction under the name of slow pre-betalipoprotein or pre-beta-lipoprotein. To the rare studies so far published on this subject, we bring here our contribution in the form of a routine analysis of the variations, and not only the presence, but also the relative concentration of the slow pre-beta-lipoproteins with regard to the rapid prebetalipoproteins. On the fasting serum, after 12 hours fasting, comparative studies of normal control subjects (104 cases) of essential hypercholesterolemia, with or without tendinous xanthomas, corresponding to type IIa (110 cases), mixed hyperlipidemia of type II + IV or III, on paper electrophoresis, corresponds usually to type IIb (204 cases) and, finally, massive endogenous hypertriglyceridemia, corresponding to type IV (95 cases). These indicate clearly the elective concentration of the band of slow pre-betalipoproteins persisting after 12 hours fasting in cases of mixed hyperlipidemia (73% of cases), whilst it is rare in the other groups (no more than 5% of cases). A more complete study of 204 cases of mixed hyperlipidemia showed that the high frequency of slow pre-betalipoproteins is situated in a fairly narrow range of relatively moderate hypertriglyceridemia, between the lower limit of 1.50 and the upper limit of 6 to 7 g/l: the maximum frequency and intensity is situated within the area of 2.50 to 4 g/l. The cases who have already had cardiovascular accidents are more often found to have this band than the cases without complications in a fairly similar age group. However, longitudinal studies, both midterm in relation to therapeutic correction, and short term throughout the day or between the 8th and 12th hour of fasting, have clearly revealed the potential labile nature of this fraction, and show the pathological nature of its sometimes massive persistence beyond the 8th hour and even beyond the 12th hour of fasting. This is a sign of pathological blocking of its transformation rather than of a constitutional lipoprotein abnormality.", "contents": "[Detection and distriburion of slow pre-betalipoprotein in agar gel electrophoresis of total serum in 204 cases of mixed hyperlipidemia]. The demonstration in certain sera by electrophoresis an Agar gel, according to Noble's technique, of a further band of intermediate pre-betalipoprotein, between the betalipoproteins and the usual rapid pre-betalipoproteins, led to the designation of this fraction under the name of slow pre-betalipoprotein or pre-beta-lipoprotein. To the rare studies so far published on this subject, we bring here our contribution in the form of a routine analysis of the variations, and not only the presence, but also the relative concentration of the slow pre-beta-lipoproteins with regard to the rapid prebetalipoproteins. On the fasting serum, after 12 hours fasting, comparative studies of normal control subjects (104 cases) of essential hypercholesterolemia, with or without tendinous xanthomas, corresponding to type IIa (110 cases), mixed hyperlipidemia of type II + IV or III, on paper electrophoresis, corresponds usually to type IIb (204 cases) and, finally, massive endogenous hypertriglyceridemia, corresponding to type IV (95 cases). These indicate clearly the elective concentration of the band of slow pre-betalipoproteins persisting after 12 hours fasting in cases of mixed hyperlipidemia (73% of cases), whilst it is rare in the other groups (no more than 5% of cases). A more complete study of 204 cases of mixed hyperlipidemia showed that the high frequency of slow pre-betalipoproteins is situated in a fairly narrow range of relatively moderate hypertriglyceridemia, between the lower limit of 1.50 and the upper limit of 6 to 7 g/l: the maximum frequency and intensity is situated within the area of 2.50 to 4 g/l. The cases who have already had cardiovascular accidents are more often found to have this band than the cases without complications in a fairly similar age group. However, longitudinal studies, both midterm in relation to therapeutic correction, and short term throughout the day or between the 8th and 12th hour of fasting, have clearly revealed the potential labile nature of this fraction, and show the pathological nature of its sometimes massive persistence beyond the 8th hour and even beyond the 12th hour of fasting. This is a sign of pathological blocking of its transformation rather than of a constitutional lipoprotein abnormality."} {"id": "PMID:180858", "title": "[Familial blepharophimosis (author's transl)].", "content": "A typical case of familial blepharophimosis is reported. The genealogical tree is reviewed up to the third generation, finding a total of seven affected individuals, 40% of the studied patients. A nervous pattern in the E.N.G. of the facial nerve was found and its possible implication in the genesis of the facial features is discussed. In the genetic study, there was a normal cariotype, and in the genealogical tree a dominant autosomic transmission, without any evident difference in the transmission related to the primitively involved sex was observed.", "contents": "[Familial blepharophimosis (author's transl)]. A typical case of familial blepharophimosis is reported. The genealogical tree is reviewed up to the third generation, finding a total of seven affected individuals, 40% of the studied patients. A nervous pattern in the E.N.G. of the facial nerve was found and its possible implication in the genesis of the facial features is discussed. In the genetic study, there was a normal cariotype, and in the genealogical tree a dominant autosomic transmission, without any evident difference in the transmission related to the primitively involved sex was observed."} {"id": "PMID:180863", "title": "[Clinical and developmental aspects of hepatoma].", "content": "We have reported here 38 cases of hepatoma observed over a period of 3 1/2 years in a Paris hospital, and recall the main circumstances of discovery of this primary tumour of the liver. Clinically, hepatomegaly with a hard, painful border, increasing rapidly in volume in a patient with a past history of alcoholism and with a poor general condition, remains the best sign. More often, decompensated cirrhosis is the only sign and may lead to the wrong diagnosis, until alphafoetoprotein estimation and laparoscopy are carried out. Unfortunately, the almost constant presence of cirrhosis, usually diffuse, and the pluricentric character of the hepatoma, make any attempt at removal immpossible. Treatment consists simply of the administration of analgesics whilst awaiting a fatal issue within 3 to 4 months. We believe that it is useful to have constantly in mind this terminal complication of cirrhosis as, at present, among the direct or associated causes of death from cirrhosis, hepatomas seem to account for about 20%.", "contents": "[Clinical and developmental aspects of hepatoma]. We have reported here 38 cases of hepatoma observed over a period of 3 1/2 years in a Paris hospital, and recall the main circumstances of discovery of this primary tumour of the liver. Clinically, hepatomegaly with a hard, painful border, increasing rapidly in volume in a patient with a past history of alcoholism and with a poor general condition, remains the best sign. More often, decompensated cirrhosis is the only sign and may lead to the wrong diagnosis, until alphafoetoprotein estimation and laparoscopy are carried out. Unfortunately, the almost constant presence of cirrhosis, usually diffuse, and the pluricentric character of the hepatoma, make any attempt at removal immpossible. Treatment consists simply of the administration of analgesics whilst awaiting a fatal issue within 3 to 4 months. We believe that it is useful to have constantly in mind this terminal complication of cirrhosis as, at present, among the direct or associated causes of death from cirrhosis, hepatomas seem to account for about 20%."} {"id": "PMID:180864", "title": "[Reflexions and thoughts about one case of acromegalic gigantism (author's transl)].", "content": "Having observed a 22 year old man with a case of acromegalic-gigantism (2,30 m.) whose growth still continued after the ablation of a hypophyseal micro-adenoma, by trans-sphenoidale tract, the authors after making various neuroendocrine comments study from a psychological point of view the myth of the giant which appears to be linked to the myth of origins, from a phylogentical point of view (for example Atlantis) as well as from the ontogenetical point of view (identification to the father). The example is particularly ambivalent: at the same time idealized (the Heros), and rejected (the Ogre)--this is explained by the evolution of the father complex, and by the connections between, on the one hand the ego, and on the other hand the ideal ego and the couple ego ideal-super ego.", "contents": "[Reflexions and thoughts about one case of acromegalic gigantism (author's transl)]. Having observed a 22 year old man with a case of acromegalic-gigantism (2,30 m.) whose growth still continued after the ablation of a hypophyseal micro-adenoma, by trans-sphenoidale tract, the authors after making various neuroendocrine comments study from a psychological point of view the myth of the giant which appears to be linked to the myth of origins, from a phylogentical point of view (for example Atlantis) as well as from the ontogenetical point of view (identification to the father). The example is particularly ambivalent: at the same time idealized (the Heros), and rejected (the Ogre)--this is explained by the evolution of the father complex, and by the connections between, on the one hand the ego, and on the other hand the ideal ego and the couple ego ideal-super ego."} {"id": "PMID:180865", "title": "Use of conjugated estrogens in eye diseases.", "content": "Presomen, a preparation of natural conjugated estrogen has been applied to 81 ophthalmologic patients. Some patients received it as a preoperative measure for the prevention of hemorrhages, others were treated with the drug in order to facilitate the absorption of vitreous and retinal hemorrhages. The effect of the preparation on capillary fragility has likewise been studied. The literature contains contradictory reports on the mode of action of conjugated estrogens. Clinical observations show conjugated estrogens suitable for the prevention of hemorrhages in connection with surgical interventions.", "contents": "Use of conjugated estrogens in eye diseases. Presomen, a preparation of natural conjugated estrogen has been applied to 81 ophthalmologic patients. Some patients received it as a preoperative measure for the prevention of hemorrhages, others were treated with the drug in order to facilitate the absorption of vitreous and retinal hemorrhages. The effect of the preparation on capillary fragility has likewise been studied. The literature contains contradictory reports on the mode of action of conjugated estrogens. Clinical observations show conjugated estrogens suitable for the prevention of hemorrhages in connection with surgical interventions."} {"id": "PMID:180867", "title": "Low postheparin plasma hepatic lipase activity in familial type IIa hyperlipoproteinemia.", "content": "A subnormal activity of postheparin plasma hepatic lipase was demonstrated in nine of 16 patients with familial type II hypercholesterolemia. On the other hand, in patients with combined hyperlipidemia (type II b) the hepatic lipase activity was mostly in upper normal range. The postheparin plasma lipoprotein lipase activity was normal in both patient groups. It is suggested that the low hepatic lipase activity may have a role in the patholgenesis of one form of familial hypercholesterolemia.", "contents": "Low postheparin plasma hepatic lipase activity in familial type IIa hyperlipoproteinemia. A subnormal activity of postheparin plasma hepatic lipase was demonstrated in nine of 16 patients with familial type II hypercholesterolemia. On the other hand, in patients with combined hyperlipidemia (type II b) the hepatic lipase activity was mostly in upper normal range. The postheparin plasma lipoprotein lipase activity was normal in both patient groups. It is suggested that the low hepatic lipase activity may have a role in the patholgenesis of one form of familial hypercholesterolemia."} {"id": "PMID:180869", "title": "Glomerular injury in patients with neoplasia.", "content": "There is considerable circumstantial evidence relating neoplasia to glomerular injury. Recently, more convincing evidence has been derived from the demonstration of tumor-associated antigen or antibody to such antigen, in relation to glomerular basement membranes in four patients with glomerular injury and cancer. The most common form of glomerulopathy reported in patients with carcinoma has been membranous glomerulonephritis. However, increased mesangial cells and matrix have also been found in some patients with hematuria and progressive renal failure. In contrast, most patients with Hodgkin's disease and glomerulopathy have had the minimal lesion-type nephrotic syndrome, which has usually responded to successful treatment of the Hodgkin's disease. Glomerular abnormalities have also been reported with chronic lymphocytic leukemia, lymphosarcoma, Waldenstrom's macroglobulinemia, and benign tumors. When there is no apparent cause, proteinuria with or without hematuria or impaired renal function should suggest the possibility of associated neoplasia, particularly in elderly patients.", "contents": "Glomerular injury in patients with neoplasia. There is considerable circumstantial evidence relating neoplasia to glomerular injury. Recently, more convincing evidence has been derived from the demonstration of tumor-associated antigen or antibody to such antigen, in relation to glomerular basement membranes in four patients with glomerular injury and cancer. The most common form of glomerulopathy reported in patients with carcinoma has been membranous glomerulonephritis. However, increased mesangial cells and matrix have also been found in some patients with hematuria and progressive renal failure. In contrast, most patients with Hodgkin's disease and glomerulopathy have had the minimal lesion-type nephrotic syndrome, which has usually responded to successful treatment of the Hodgkin's disease. Glomerular abnormalities have also been reported with chronic lymphocytic leukemia, lymphosarcoma, Waldenstrom's macroglobulinemia, and benign tumors. When there is no apparent cause, proteinuria with or without hematuria or impaired renal function should suggest the possibility of associated neoplasia, particularly in elderly patients."} {"id": "PMID:180871", "title": "The effects of calcium and phosphorus in hemodialysis.", "content": "Combined use of Ca supplements (orally or by dialysis) to circumvent decreased intestinal Ca absorption and aluminum compounds to reduce plasma [Pi] has been demonstrated to decrease plasma [iPTH], to normal or near normal in many patients, and to decrease the percentage of bone surface involved in bone resorption. A highly significant positive relationship between change in plasma [iPTH] and bone resorbing surface has been reported. It seems evident, therefore, that PTH must be a major factor in the bone resorption of chronic renal failure, despite the relative skeletal resistance to PTH. As a result, correction of factors that increase PTH secretion should be considered a prime goal of therapy in these patients. The osteomalacic element of renal osteodystrophy, on the other hand, is only partially controlled by these maneuvers and probably requires the additional use of vitamin D or one of its active metabolites for full correction.", "contents": "The effects of calcium and phosphorus in hemodialysis. Combined use of Ca supplements (orally or by dialysis) to circumvent decreased intestinal Ca absorption and aluminum compounds to reduce plasma [Pi] has been demonstrated to decrease plasma [iPTH], to normal or near normal in many patients, and to decrease the percentage of bone surface involved in bone resorption. A highly significant positive relationship between change in plasma [iPTH] and bone resorbing surface has been reported. It seems evident, therefore, that PTH must be a major factor in the bone resorption of chronic renal failure, despite the relative skeletal resistance to PTH. As a result, correction of factors that increase PTH secretion should be considered a prime goal of therapy in these patients. The osteomalacic element of renal osteodystrophy, on the other hand, is only partially controlled by these maneuvers and probably requires the additional use of vitamin D or one of its active metabolites for full correction."} {"id": "PMID:180868", "title": "Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-gu\u00e9rin).", "content": "CD-1 or OF-1 mice were inoculated intravenously with 1 mg per mouse (i.e. about 10(6) live bacilli) of Pasteur Institute BCG and challenged 15 to 31 days later with the following viruses introduced by various routes: encephalomyocarditis, murine hepatitis, type 1 and 2 herpes simplex, foot-and-mouth disease and A0 and A2 influenza viruses. In most cases, BCG-inoculated mice exhibited a significantly higher resistance to these lethal infections than control mice (overall survival in control: 18%; in BCG-inoculated mice: 41%). Enhancement of resistance by BCG was especially marked in infections with encephalomyocarditis, herpes simplex type 1 and influenza A2 viruses. Intercurrent infection of BCG-inoculated mice with non lethal doses of viruses did not abrogate their resistance towards subsequent challenge with lethal doses of an unrelated virus. The possible mechanisms of this enhancing effect of BCG on host's resistance are discussed in the light of the known effects of this immunostimulating agent on the various facets of the immune response and of the respective roles the latter play in the defence against virus infections.", "contents": "Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-gu\u00e9rin). CD-1 or OF-1 mice were inoculated intravenously with 1 mg per mouse (i.e. about 10(6) live bacilli) of Pasteur Institute BCG and challenged 15 to 31 days later with the following viruses introduced by various routes: encephalomyocarditis, murine hepatitis, type 1 and 2 herpes simplex, foot-and-mouth disease and A0 and A2 influenza viruses. In most cases, BCG-inoculated mice exhibited a significantly higher resistance to these lethal infections than control mice (overall survival in control: 18%; in BCG-inoculated mice: 41%). Enhancement of resistance by BCG was especially marked in infections with encephalomyocarditis, herpes simplex type 1 and influenza A2 viruses. Intercurrent infection of BCG-inoculated mice with non lethal doses of viruses did not abrogate their resistance towards subsequent challenge with lethal doses of an unrelated virus. The possible mechanisms of this enhancing effect of BCG on host's resistance are discussed in the light of the known effects of this immunostimulating agent on the various facets of the immune response and of the respective roles the latter play in the defence against virus infections."} {"id": "PMID:180879", "title": "The pharmacology of the pineal gland.", "content": "Only recently have a sufficient number of publications been available to legitimize a review of the pharmacology of the mammalian pineal organ. Two decades ago Kitay & Altschule reviewed the world literature on pineal physiology, which comprises several thousand papers, and concluded only that removal of the pineal, or administration of pineal extracts, somehow affected pigmentation in lower vertebrates and gonadal function in mammals (1). As the studies described below demonstrate, much more information is now available concerning the pharmacology of the pineal. This review subdivides present knowledge into two areas: (a) the effects on mammals of administering pineal extracts or pure synthetic or natural pineal constituents and (b) the effects of drugs and hormones on the pineal itself. As might be anticipated, the bulk of studies cited in both categories deals with the pineal hormone, melatonin. Melatonin was first isolated from bovine pineal extracts in 1958 by Lerner and his colleagues (2), who used as a marker the capacity of the hormone to aggregate the pigment granules in amphibian melanophores around the cell nucleus. Five years later, Wurtman et al (3) showed that melatonin affected a physiological function in mammals, that is, the size and secretion of the ovary, and subsequent studies have demonstrated that melatonin administration also modifies the growth, composition, and functional activities of numerous other organs. Only recently an assay was developed that allows quantification of the melatonin in human urine (4). The concentrations of the compound vary with a characteristic daily rhythm, peaking at night. The pineal's apparent role as the sole or major source of melatonin, the presence of melatonin in urine, and the demonstration that physiologic effects follow a pinealectomy or the administration of melatomin seem to justify labeling it a pineal hormone. Melatonin synthesis and pineal biosynthetic activity are generally controlled by the sympathetic nerves of this organ (5,6). Therefore, it should not be surprising that drugs known to modify the synthesis, release, or metabolism of norepinephrine in peripheral organs also affect pineal function. Melatonin is itself a derivative of another biogenic amine, serotonin, whose metabolism and actions are also affected by numerous drugs. Indeed, the pineal has often provided an apt tool for examining monoaminergic mechanisms for pharmacologists not specifically concerned with its particular functional properties.", "contents": "The pharmacology of the pineal gland. Only recently have a sufficient number of publications been available to legitimize a review of the pharmacology of the mammalian pineal organ. Two decades ago Kitay & Altschule reviewed the world literature on pineal physiology, which comprises several thousand papers, and concluded only that removal of the pineal, or administration of pineal extracts, somehow affected pigmentation in lower vertebrates and gonadal function in mammals (1). As the studies described below demonstrate, much more information is now available concerning the pharmacology of the pineal. This review subdivides present knowledge into two areas: (a) the effects on mammals of administering pineal extracts or pure synthetic or natural pineal constituents and (b) the effects of drugs and hormones on the pineal itself. As might be anticipated, the bulk of studies cited in both categories deals with the pineal hormone, melatonin. Melatonin was first isolated from bovine pineal extracts in 1958 by Lerner and his colleagues (2), who used as a marker the capacity of the hormone to aggregate the pigment granules in amphibian melanophores around the cell nucleus. Five years later, Wurtman et al (3) showed that melatonin affected a physiological function in mammals, that is, the size and secretion of the ovary, and subsequent studies have demonstrated that melatonin administration also modifies the growth, composition, and functional activities of numerous other organs. Only recently an assay was developed that allows quantification of the melatonin in human urine (4). The concentrations of the compound vary with a characteristic daily rhythm, peaking at night. The pineal's apparent role as the sole or major source of melatonin, the presence of melatonin in urine, and the demonstration that physiologic effects follow a pinealectomy or the administration of melatomin seem to justify labeling it a pineal hormone. Melatonin synthesis and pineal biosynthetic activity are generally controlled by the sympathetic nerves of this organ (5,6). Therefore, it should not be surprising that drugs known to modify the synthesis, release, or metabolism of norepinephrine in peripheral organs also affect pineal function. Melatonin is itself a derivative of another biogenic amine, serotonin, whose metabolism and actions are also affected by numerous drugs. Indeed, the pineal has often provided an apt tool for examining monoaminergic mechanisms for pharmacologists not specifically concerned with its particular functional properties."} {"id": "PMID:180880", "title": "[Effect of antibiotics on the resistance of white mice to C1. perfringens toxin].", "content": "The effect of potassium benzylpenicillin, streptomycin sulfate and chlortetracycline on experimental gangrenous intoxication was studied. When the antibiotics were injected before intoxication, the albino mice resistance did not significantly change. When the antibiotics were injected immediately after the toxin administration, the resistance of the test animals markedly decreased.", "contents": "[Effect of antibiotics on the resistance of white mice to C1. perfringens toxin]. The effect of potassium benzylpenicillin, streptomycin sulfate and chlortetracycline on experimental gangrenous intoxication was studied. When the antibiotics were injected before intoxication, the albino mice resistance did not significantly change. When the antibiotics were injected immediately after the toxin administration, the resistance of the test animals markedly decreased."} {"id": "PMID:180881", "title": "Rapid microbiological assay for chloramphenicol and tetracyclines.", "content": "An agar diffusion assay for chloramphenicol and tetracyclines is described, using inhibition of hemolysis by Clostridium perfringens as a biological indicator of antimicrobial activity. Well-defined zones formed after a 1.5- to 2-h incubation in an anaerobic chamber or after 3 h using a GasPak system. Serum levels of chloramphenicol as low as 2.0 mug/ml could be reproducibly determined with this method. Concurrent presence of gentamicin did not influence the assay. Levels of penicillin G were also reproducibly determined with this method, although use of stable zones of growth inhibition which would form after overnight incubation were a more convenient end point for this bactericidal drug. The hemolytic assay with C. perfringens is a reproducible, accurate, and rapid method for determination of levels for chloramphenicol and tetracyclines.", "contents": "Rapid microbiological assay for chloramphenicol and tetracyclines. An agar diffusion assay for chloramphenicol and tetracyclines is described, using inhibition of hemolysis by Clostridium perfringens as a biological indicator of antimicrobial activity. Well-defined zones formed after a 1.5- to 2-h incubation in an anaerobic chamber or after 3 h using a GasPak system. Serum levels of chloramphenicol as low as 2.0 mug/ml could be reproducibly determined with this method. Concurrent presence of gentamicin did not influence the assay. Levels of penicillin G were also reproducibly determined with this method, although use of stable zones of growth inhibition which would form after overnight incubation were a more convenient end point for this bactericidal drug. The hemolytic assay with C. perfringens is a reproducible, accurate, and rapid method for determination of levels for chloramphenicol and tetracyclines."} {"id": "PMID:180882", "title": "Demonstration of solids-associated virus in wastewater and sludge.", "content": "Data presented demonstrate the relatively high multiplicity of solids-associated virus in field samples, i.e., wastewater, sludge, and soils. Influent, effluent, and chlorinated effluent samples showed 16.1 to 100% of the total virus demonstrated in samples to be solids associated. Three techniques for freeing solids-associated virus are described and compared. Using sonication of solids and polyethylene glycol concentration, virus was demonstrated in fully digested sludge (60 days at 34 C), sand at the site of a sewer leak, and dried sludge cake and mud 900 m downstream from a sewage disposal site. These data emphasize the inadequacy of virus concentration techniques that do not include the processing of solids. In situ elution failed to free solids-associated virus.", "contents": "Demonstration of solids-associated virus in wastewater and sludge. Data presented demonstrate the relatively high multiplicity of solids-associated virus in field samples, i.e., wastewater, sludge, and soils. Influent, effluent, and chlorinated effluent samples showed 16.1 to 100% of the total virus demonstrated in samples to be solids associated. Three techniques for freeing solids-associated virus are described and compared. Using sonication of solids and polyethylene glycol concentration, virus was demonstrated in fully digested sludge (60 days at 34 C), sand at the site of a sewer leak, and dried sludge cake and mud 900 m downstream from a sewage disposal site. These data emphasize the inadequacy of virus concentration techniques that do not include the processing of solids. In situ elution failed to free solids-associated virus."} {"id": "PMID:180883", "title": "Morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or peptone.", "content": "The morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or on peptone in shake-culture were compared using transmission and scanning electron microscopy. The fungus grew as hollow mycelial balls surrounding individual hydrocarbon droplets on n-hexadecane and as solid mycelial balls on peptone. A dense layer of fungal mycelium that showed irregular forms, fusion, and increase in hyphal size formed at the hydrocarbon-water interface. Inclusions were present in the hexadecane-grown fungus that were absent when the Penicillium sp. was grown on peptone. Problems of fixation made it difficult to differentiate detailed changes in the cytoplasm when the fungus was examined with the transmission electron microscope.", "contents": "Morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or peptone. The morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or on peptone in shake-culture were compared using transmission and scanning electron microscopy. The fungus grew as hollow mycelial balls surrounding individual hydrocarbon droplets on n-hexadecane and as solid mycelial balls on peptone. A dense layer of fungal mycelium that showed irregular forms, fusion, and increase in hyphal size formed at the hydrocarbon-water interface. Inclusions were present in the hexadecane-grown fungus that were absent when the Penicillium sp. was grown on peptone. Problems of fixation made it difficult to differentiate detailed changes in the cytoplasm when the fungus was examined with the transmission electron microscope."} {"id": "PMID:180884", "title": "Growth of Clostridium tertium and Clostridium septicum in chemically defined media.", "content": "Defined media for the growth of Clostridium tertium and Clostridium septicum are described. The requirements for growth of these two species are compared with each other and with those of Clostridium perfringens.", "contents": "Growth of Clostridium tertium and Clostridium septicum in chemically defined media. Defined media for the growth of Clostridium tertium and Clostridium septicum are described. The requirements for growth of these two species are compared with each other and with those of Clostridium perfringens."} {"id": "PMID:180885", "title": "Influence of starch source on sporulation and enterotoxin production by Clostridium perfringens type A.", "content": "Of 16 different starch preparations tested, Clostridium perfringes NCTC 8798 yielded maximum sporulation and enterotoxin formation when ICN-soluble starch was included in Duncan and Strong sporulation medium. In general soluble starches were better than potato, corn, or arrowroot starch with regard to these two parameters.", "contents": "Influence of starch source on sporulation and enterotoxin production by Clostridium perfringens type A. Of 16 different starch preparations tested, Clostridium perfringes NCTC 8798 yielded maximum sporulation and enterotoxin formation when ICN-soluble starch was included in Duncan and Strong sporulation medium. In general soluble starches were better than potato, corn, or arrowroot starch with regard to these two parameters."} {"id": "PMID:180886", "title": "Bacteriological quality and shelf life of ground beef.", "content": "The bacteriological quality of unfrozen raw ground beef was evaluated after 0, 3, 6, 9, 12, 15, and 18 days of storage at 29 +/- 1 F (-1.7 +/- 0.6 C). At the time of fabrication, all of the ground beef samples contained 10(6) or fewer total aerobic and psychrotrophic bacteria/g; 81% contained 100 or fewer coliforms/g; 94% contained 100 or fewer Escherichia coli/g; and all of the samples contained 100 or fewer coagulase-positive Staphylococcus aureus and Clostridium perfringens/g. Total aerobic and psychrotrophic bacteria increased by 1 log between 3 and 18 days of storage. Coliform and E. coli counts decreased during storage, whereas coagulase-positive S. aureus and C. perfringens counts did not change significantly. These data indicate that meat processors, wholesalers, and retailers could improve the bacteriological quality and prolong the shelf life of ground beef packaged in oxygen-impermeable film if the temperature of product never exceeded 29 +/- 1 F (-1.7 +/- 0.6 C).", "contents": "Bacteriological quality and shelf life of ground beef. The bacteriological quality of unfrozen raw ground beef was evaluated after 0, 3, 6, 9, 12, 15, and 18 days of storage at 29 +/- 1 F (-1.7 +/- 0.6 C). At the time of fabrication, all of the ground beef samples contained 10(6) or fewer total aerobic and psychrotrophic bacteria/g; 81% contained 100 or fewer coliforms/g; 94% contained 100 or fewer Escherichia coli/g; and all of the samples contained 100 or fewer coagulase-positive Staphylococcus aureus and Clostridium perfringens/g. Total aerobic and psychrotrophic bacteria increased by 1 log between 3 and 18 days of storage. Coliform and E. coli counts decreased during storage, whereas coagulase-positive S. aureus and C. perfringens counts did not change significantly. These data indicate that meat processors, wholesalers, and retailers could improve the bacteriological quality and prolong the shelf life of ground beef packaged in oxygen-impermeable film if the temperature of product never exceeded 29 +/- 1 F (-1.7 +/- 0.6 C)."} {"id": "PMID:180887", "title": "Inactivation of poliovirus in digested sludge.", "content": "The effect of anaerobically digested sludge on poliovirus during incubation at temperatures between 28 and 4 C was studied. Although virus was fully recoverable from sludge, its infectivity decreased in proportion to the time and temperature of incubation. The rate ranged from greater than 1 log per day at 28 C to about 1 log every 5 days at 4 C. The mechanism of inactivation was studied at the lower temperature where the sedimentation coefficients of most inactivated particles were not detectably modified. The ribonucleic acid (RNA) of these particles appeared to have been nicked and had an average sedimentation value about 70% that of RNA from infectious virus. Since the specific infectivity of RNA from particles recovered from sludge was directly proportional to that of the particles from which it was extracted, loss of infectivity was probably due to inactivation of RNA. Some breakdown was also found in the two largest viral proteins of inactivated particles. Thus, the mechanism of inactivation may be cleavage of viral proteins followed by nicking of encapsulated RNA. Because no virucidal activity was found in raw sludge, this component of digested sludge appears to be a product of the digestion process.", "contents": "Inactivation of poliovirus in digested sludge. The effect of anaerobically digested sludge on poliovirus during incubation at temperatures between 28 and 4 C was studied. Although virus was fully recoverable from sludge, its infectivity decreased in proportion to the time and temperature of incubation. The rate ranged from greater than 1 log per day at 28 C to about 1 log every 5 days at 4 C. The mechanism of inactivation was studied at the lower temperature where the sedimentation coefficients of most inactivated particles were not detectably modified. The ribonucleic acid (RNA) of these particles appeared to have been nicked and had an average sedimentation value about 70% that of RNA from infectious virus. Since the specific infectivity of RNA from particles recovered from sludge was directly proportional to that of the particles from which it was extracted, loss of infectivity was probably due to inactivation of RNA. Some breakdown was also found in the two largest viral proteins of inactivated particles. Thus, the mechanism of inactivation may be cleavage of viral proteins followed by nicking of encapsulated RNA. Because no virucidal activity was found in raw sludge, this component of digested sludge appears to be a product of the digestion process."} {"id": "PMID:180888", "title": "Isolation of Pseudomonas aeruginosa and other bacterial species from ornamental aquarium plants.", "content": "Ornamental aquarium plants were demonstrated to carry as many as 10(8) viable mesophilic bacteria per g. Gram-negative organisms predominated among the 19 genera of bacteria identified. Pseudomonas aeruginosa was readily isolated from 53% of the samples tested.", "contents": "Isolation of Pseudomonas aeruginosa and other bacterial species from ornamental aquarium plants. Ornamental aquarium plants were demonstrated to carry as many as 10(8) viable mesophilic bacteria per g. Gram-negative organisms predominated among the 19 genera of bacteria identified. Pseudomonas aeruginosa was readily isolated from 53% of the samples tested."} {"id": "PMID:180889", "title": "Production of infectious Epstein-Barr virus by using an intermittent culture collection system.", "content": "Procedures were developed to produce infectious Epstein-Barr virus in large glass fermentors with limited mechanical agitation by using an intermittent culture collection system. The system appears quite suitable for use in fermentation vessels of 50 liters or larger.", "contents": "Production of infectious Epstein-Barr virus by using an intermittent culture collection system. Procedures were developed to produce infectious Epstein-Barr virus in large glass fermentors with limited mechanical agitation by using an intermittent culture collection system. The system appears quite suitable for use in fermentation vessels of 50 liters or larger."} {"id": "PMID:180905", "title": "Combinations of antimicrobial agents: II. The in vitro sensitivity of 52 strains of proteus species to sulphafurazole, polymyxins and combinations of sulphafurazole and polymyxins.", "content": "The sensitivity of 52 strains of Proteus species to sulphafurazole, polymyxins and the combinations of sulphafurazole and polymyxins was determined by means of discs and trays. It was found that 2 and 6 strains, respectively, were sensitive to discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively, 41 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 50 mug colistin, respectively, and 38 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively. The tray method proved that 2 and 5 strains were sensitive to 25 and 200 mug sulphafurazole, respectively, and that 1, 2 and 3 strains were sensitive to 25, 50 and 100 mug polymyxin B, respectively. Also 41 strains were sensitive to the combination of 100 mug sulphafurazole and 25 mug colistin and 38 strains were sensitive to the combination of 25 mug sulphafurazole and 6.3 mug polymyxin B. There was good agreement between the results of the disc and of the tray studies. The synergism between sulphonamides and polymyxins may offer therapeutic possibilities.", "contents": "Combinations of antimicrobial agents: II. The in vitro sensitivity of 52 strains of proteus species to sulphafurazole, polymyxins and combinations of sulphafurazole and polymyxins. The sensitivity of 52 strains of Proteus species to sulphafurazole, polymyxins and the combinations of sulphafurazole and polymyxins was determined by means of discs and trays. It was found that 2 and 6 strains, respectively, were sensitive to discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively, 41 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 50 mug colistin, respectively, and 38 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively. The tray method proved that 2 and 5 strains were sensitive to 25 and 200 mug sulphafurazole, respectively, and that 1, 2 and 3 strains were sensitive to 25, 50 and 100 mug polymyxin B, respectively. Also 41 strains were sensitive to the combination of 100 mug sulphafurazole and 25 mug colistin and 38 strains were sensitive to the combination of 25 mug sulphafurazole and 6.3 mug polymyxin B. There was good agreement between the results of the disc and of the tray studies. The synergism between sulphonamides and polymyxins may offer therapeutic possibilities."} {"id": "PMID:180906", "title": "Multiple palmoplantar histiocytomas.", "content": "Four patients had multiple histiocytomas involving the palms and soles; we describe the clinical and histologic features of their disorder. Multiple lesions of histiocytoma are rare, and their occurrence on the palms or the soles has not been reported, to our knowledge. Whorled patterns of intertwining bundles of histiocytic cells and fibers were seen predominantly and most frequently on histologic examination. No recurrences were noted during a follow-up period of up to two years after removal of the lesions. They appear to be distinct from juvenile fibromatoses and eruptive histiocytomas.", "contents": "Multiple palmoplantar histiocytomas. Four patients had multiple histiocytomas involving the palms and soles; we describe the clinical and histologic features of their disorder. Multiple lesions of histiocytoma are rare, and their occurrence on the palms or the soles has not been reported, to our knowledge. Whorled patterns of intertwining bundles of histiocytic cells and fibers were seen predominantly and most frequently on histologic examination. No recurrences were noted during a follow-up period of up to two years after removal of the lesions. They appear to be distinct from juvenile fibromatoses and eruptive histiocytomas."} {"id": "PMID:180907", "title": "Recessive hypophosphataemic rickets, and possible aetiology of the 'vitamin D-resistant' syndrome.", "content": "Two out of 3 children of a first-cousin marriage presented with severe rickets in infancy and are now adult. Their disease has shown continued activity, marked resistance to treatment with vitamin D, early fusion of cranial sutures, greatly increased bone density, nerve deafness, and life-long hypophosphataemia unaffected by treatment. Both parents and a third sib were normal clinically and biochemically. Blood grouping supported both stated paternity and parental consanguinity. Genetics of this unique disease can only be explained satisfactorily on the basis of autosomal recessive transmission, a mode not previously reported in primary hypophosphataemia. This homozygous disease resembles an exaggerated form of common X-linked rickets, though it is caused by a different gene. Although rare, it is particularly important because of the information it provides on the pathogenesis of both forms. We propose that both syndromes may result from multiple target organ unresponsiveness to 1,25-dihydroxycholecalciferol in intestine, kidney, bone, and parathyroid gland.", "contents": "Recessive hypophosphataemic rickets, and possible aetiology of the 'vitamin D-resistant' syndrome. Two out of 3 children of a first-cousin marriage presented with severe rickets in infancy and are now adult. Their disease has shown continued activity, marked resistance to treatment with vitamin D, early fusion of cranial sutures, greatly increased bone density, nerve deafness, and life-long hypophosphataemia unaffected by treatment. Both parents and a third sib were normal clinically and biochemically. Blood grouping supported both stated paternity and parental consanguinity. Genetics of this unique disease can only be explained satisfactorily on the basis of autosomal recessive transmission, a mode not previously reported in primary hypophosphataemia. This homozygous disease resembles an exaggerated form of common X-linked rickets, though it is caused by a different gene. Although rare, it is particularly important because of the information it provides on the pathogenesis of both forms. We propose that both syndromes may result from multiple target organ unresponsiveness to 1,25-dihydroxycholecalciferol in intestine, kidney, bone, and parathyroid gland."} {"id": "PMID:180911", "title": "[Rapid diagnosis of respiratory viral disease by means of indirect immunofluorescence test].", "content": "Indirect immunofluorescence test was employed to detect respiratory virus antigens in pharyngeal secretions. Parainfluenza virus type 1-3 sera gave positive results in 19 out of 40 patients with acute respiratory infections tested, mainly among children affected by \"viral croup\". The reliability of the test for the rapid diagnosis of respiratory infections is discussed.", "contents": "[Rapid diagnosis of respiratory viral disease by means of indirect immunofluorescence test]. Indirect immunofluorescence test was employed to detect respiratory virus antigens in pharyngeal secretions. Parainfluenza virus type 1-3 sera gave positive results in 19 out of 40 patients with acute respiratory infections tested, mainly among children affected by \"viral croup\". The reliability of the test for the rapid diagnosis of respiratory infections is discussed."} {"id": "PMID:180916", "title": "Evaluation of \"instant\" preparation of the colon with povidone-iodine.", "content": "The antimicrobial effect of 20 minutes exposure to 10% povidone-iodine solution and to 5% neomycin-erythromycin solution was evaluated in vitro in 6 suspensions of dog feces. Povidone-iodine eliminated aerobic growth (P less than 0.001) and reduced anaerobes 4.01 +/- 1.06 (P less than 0.02); C. perfringens was the only anaerobic organism grown. Forty unprepared dogs underwent resection of the sigmoid colon and primary anastomosis. Twenty received normal saline and 20 povidone-iodine injected intraluminally immediately before resection. The colon contents of povidone-iodine treated dogs grew only 0.07 +/- 0.07 aerobes and 3.74 +/- 0.49 anaerobes (all Clostridia) (log10/ml colon contents) (P less than 0.001). All povidone-iodine dogs survived 3 weeks with no anastomotic leaks; three controls died from anastomotic leak within the first week (P = 0.12). Reexploration of survivors revealed less perianastomotic reaction in the povidone-iodine group. Twenty minutes exposure to povidone-iodine produced a significant decrease in bacterial counts in vitro and in unprepared sigmoid colon. No adverse effects were demonstrated.", "contents": "Evaluation of \"instant\" preparation of the colon with povidone-iodine. The antimicrobial effect of 20 minutes exposure to 10% povidone-iodine solution and to 5% neomycin-erythromycin solution was evaluated in vitro in 6 suspensions of dog feces. Povidone-iodine eliminated aerobic growth (P less than 0.001) and reduced anaerobes 4.01 +/- 1.06 (P less than 0.02); C. perfringens was the only anaerobic organism grown. Forty unprepared dogs underwent resection of the sigmoid colon and primary anastomosis. Twenty received normal saline and 20 povidone-iodine injected intraluminally immediately before resection. The colon contents of povidone-iodine treated dogs grew only 0.07 +/- 0.07 aerobes and 3.74 +/- 0.49 anaerobes (all Clostridia) (log10/ml colon contents) (P less than 0.001). All povidone-iodine dogs survived 3 weeks with no anastomotic leaks; three controls died from anastomotic leak within the first week (P = 0.12). Reexploration of survivors revealed less perianastomotic reaction in the povidone-iodine group. Twenty minutes exposure to povidone-iodine produced a significant decrease in bacterial counts in vitro and in unprepared sigmoid colon. No adverse effects were demonstrated."} {"id": "PMID:180912", "title": "[Studies on the physiopathology of cholera in Bari].", "content": "During a small epidemic of cholera in South Italy in summer of 1973, the infection showed some peculiarities and differences in comparison with cholera classic picture of Asiatic areas. In this paper epidemiological, pathogenetic, clinical and biochemical data of patients admitted to the Institute of Infectious Diseases of Bari are reported. The age of the majority of patients (over 50) is an important factor for understanding cause of infection; but also preexistent basal diseases are responsible of severe course of infection. In fact, in spite of low mortality (2/70), in many cases the course of disease has been complicated by metabolic disorders. Also cardio-vascular conditions have influenced course of infection. The Authors discuss the causes of this atypic behaviour of cholera in South Italy.", "contents": "[Studies on the physiopathology of cholera in Bari]. During a small epidemic of cholera in South Italy in summer of 1973, the infection showed some peculiarities and differences in comparison with cholera classic picture of Asiatic areas. In this paper epidemiological, pathogenetic, clinical and biochemical data of patients admitted to the Institute of Infectious Diseases of Bari are reported. The age of the majority of patients (over 50) is an important factor for understanding cause of infection; but also preexistent basal diseases are responsible of severe course of infection. In fact, in spite of low mortality (2/70), in many cases the course of disease has been complicated by metabolic disorders. Also cardio-vascular conditions have influenced course of infection. The Authors discuss the causes of this atypic behaviour of cholera in South Italy."} {"id": "PMID:180915", "title": "Cyclic AMP.", "content": "Cyclic AMP is believed to be the intracellular agent which mediates the action of many hormones on their target cell. The mechanisms by which the nucleotide controls glycogen metabolism in liver and skeletal muscle seem to be firmly established. Data relevant to this area of research are selectively reviewed. In addition, the evidence is reviewed for and against a role for cyclic AMP in the regulation of a variety of other cellular functions including: cardiac contractility, smooth muscle relaxation, platelet aggregation, salivary gland amylase secretion, pancreatic exocrine secretion, and gastric acid secretion.", "contents": "Cyclic AMP. Cyclic AMP is believed to be the intracellular agent which mediates the action of many hormones on their target cell. The mechanisms by which the nucleotide controls glycogen metabolism in liver and skeletal muscle seem to be firmly established. Data relevant to this area of research are selectively reviewed. In addition, the evidence is reviewed for and against a role for cyclic AMP in the regulation of a variety of other cellular functions including: cardiac contractility, smooth muscle relaxation, platelet aggregation, salivary gland amylase secretion, pancreatic exocrine secretion, and gastric acid secretion."} {"id": "PMID:180917", "title": "Identification of the jaundiced infant who is likely to recover without surgical intervention.", "content": "A series of 32 infants with persistant jaundice in whom an unequivocal differentiation between intrahepatic cholestasis and biliary atresia could not be made is reviewed. A protocol including Lipoprotein-X (LP-X) determinations before and after a short course of cholestyramine (CSM) was carried out in all. A fall in serum LP-X after CSM indicates the presence of patent extrahepatic bile ducts (even microscopic) which will function without benefit of hepatic portoenterostomy. A rise in LP-X levels after CSM means an atretic biliary system. The LP-X, CSM protocol was not able to differentiate between the anatomical variants of biliary atresia that may respond to hepatic portoenterostomy and those that will not. Patent bile ducts (even microscopic) in the porta hepatis and/or proximal hepatoduodenal ligament, which are in continuity with intrahepatic ducts, must be present if hepatic portoenterostomy is to be successful. None of our 12 infants undergoing hepatic portoenterostomy showed evidence of bile excretion after the procedure. Microscopic study of serial sections taken through the excised hepatoduodenal ligament tissues of these 12 infants revealed that none had anatomical findings conducive to the success of the operation.", "contents": "Identification of the jaundiced infant who is likely to recover without surgical intervention. A series of 32 infants with persistant jaundice in whom an unequivocal differentiation between intrahepatic cholestasis and biliary atresia could not be made is reviewed. A protocol including Lipoprotein-X (LP-X) determinations before and after a short course of cholestyramine (CSM) was carried out in all. A fall in serum LP-X after CSM indicates the presence of patent extrahepatic bile ducts (even microscopic) which will function without benefit of hepatic portoenterostomy. A rise in LP-X levels after CSM means an atretic biliary system. The LP-X, CSM protocol was not able to differentiate between the anatomical variants of biliary atresia that may respond to hepatic portoenterostomy and those that will not. Patent bile ducts (even microscopic) in the porta hepatis and/or proximal hepatoduodenal ligament, which are in continuity with intrahepatic ducts, must be present if hepatic portoenterostomy is to be successful. None of our 12 infants undergoing hepatic portoenterostomy showed evidence of bile excretion after the procedure. Microscopic study of serial sections taken through the excised hepatoduodenal ligament tissues of these 12 infants revealed that none had anatomical findings conducive to the success of the operation."} {"id": "PMID:180918", "title": "Gas gangrene: review of 34 cases.", "content": "High morbidity and mortality continue to result from gas gangrene, despite the use of aggressive modes of therapy. Between 1967 and 1973, 34 patients with gas gangrene were seen at the University of Maryland Hospital; 11 (32.3%) died. Clostridium perfringens was recovered from the wounds in 79% of the cases and from the blood in 15%. Eighty-five percent of the wounds contained one or more organisms in addition to C perfringens, with as many as seven organisms recovered from some wounds. Twenty-nine patients received hyperbaric oxygen treatments, as well as the more conventional antibiotic drugs; it was not possible to assess the value of this added therapy. Gangrene of the abdominal wall resulted in a higher (50%) mortality than gangrene of an extremity (24%). Presence of normal or depressed white blood cell counts, decreased platelet counts, and abnormal renal or liver functions all denoted a poor prognosis.", "contents": "Gas gangrene: review of 34 cases. High morbidity and mortality continue to result from gas gangrene, despite the use of aggressive modes of therapy. Between 1967 and 1973, 34 patients with gas gangrene were seen at the University of Maryland Hospital; 11 (32.3%) died. Clostridium perfringens was recovered from the wounds in 79% of the cases and from the blood in 15%. Eighty-five percent of the wounds contained one or more organisms in addition to C perfringens, with as many as seven organisms recovered from some wounds. Twenty-nine patients received hyperbaric oxygen treatments, as well as the more conventional antibiotic drugs; it was not possible to assess the value of this added therapy. Gangrene of the abdominal wall resulted in a higher (50%) mortality than gangrene of an extremity (24%). Presence of normal or depressed white blood cell counts, decreased platelet counts, and abnormal renal or liver functions all denoted a poor prognosis."} {"id": "PMID:180913", "title": "[Late stages in the replicative cycle of human cytomegaloviruses in diploid cells. Ultrastructural study].", "content": "An ultrastructural study of late stages of the replicative cycle of human cytomegalovirus (CMV) in human embryo fibroblasts cell cultures has been performed. Nucleocapsids are observed only inside the intranuclear inclusion. They mature apparently by taking the envelope from the structural components of microvescicular systems reaching from the nuclear membrane the periphery of the nuclear inclusion. However, some capsids reach \"naked\" the cytoplasm and then take the envelope from cytoplasmic membranes. In the cytoplasm homogeneous \"dense material\" and \"dense microbodies\" are present; in extracellular space enveloped \"dense microbodies\" are scattered among virions. The peculiar envelopment of CMV capsids, not yet described in the literature, is discussed and the typical ultrastructural cytopathology of CMV infected cells is indicated as an useful tool in diagnostic virology.", "contents": "[Late stages in the replicative cycle of human cytomegaloviruses in diploid cells. Ultrastructural study]. An ultrastructural study of late stages of the replicative cycle of human cytomegalovirus (CMV) in human embryo fibroblasts cell cultures has been performed. Nucleocapsids are observed only inside the intranuclear inclusion. They mature apparently by taking the envelope from the structural components of microvescicular systems reaching from the nuclear membrane the periphery of the nuclear inclusion. However, some capsids reach \"naked\" the cytoplasm and then take the envelope from cytoplasmic membranes. In the cytoplasm homogeneous \"dense material\" and \"dense microbodies\" are present; in extracellular space enveloped \"dense microbodies\" are scattered among virions. The peculiar envelopment of CMV capsids, not yet described in the literature, is discussed and the typical ultrastructural cytopathology of CMV infected cells is indicated as an useful tool in diagnostic virology."} {"id": "PMID:180914", "title": "Anti-neuraminidase antibody response in hamsters experimentally infected with Sendai virus.", "content": "Investigations were performed to study the behaviour of neuraminidase-inhibiting (n.i.a.) and, by comparison, of neutralizing, hemagglutinin-inhibiting (h.i.a.) and anti-S and anti-V complement-fixing (c.f.a.) antibodies in hamsters inoculated intranasally with a Sendai virus strain of recent isolation. Moreover the distribution of the virus in the respiratory tract was followed. Preliminary experiences were done to assure a correct performance of the neuraminidase-inhibition test. First of all the optimal pH and then the influence of the normal hamster serum on the enzyme activity were evaluated. The n.i.a. as well as h.i.a. and anti-S and anti-V c.f.a. were demonstrable from day 6th after infection, neutralizing antibody from 8th day. The n.i.a. reached the peak of 24 days, that is later than the other types of antibodies, and started to decline after 1 month, together with the drop of the h.i.a and c.f.a. On the contrary the neutralizing antibody persisted at high titres till the end of the observation period (75 days). Detectable antibody response was coincidental with a marked drop in the titers of virus recovered from the respiratory tract. Because of the association of both hemagglutinating and neuraminidase activities with the same Sendai glycoprotein, it is stressed the possibility that hemagglutination-inhibition and neutraminidase-inibition tests titrate the same antibody.", "contents": "Anti-neuraminidase antibody response in hamsters experimentally infected with Sendai virus. Investigations were performed to study the behaviour of neuraminidase-inhibiting (n.i.a.) and, by comparison, of neutralizing, hemagglutinin-inhibiting (h.i.a.) and anti-S and anti-V complement-fixing (c.f.a.) antibodies in hamsters inoculated intranasally with a Sendai virus strain of recent isolation. Moreover the distribution of the virus in the respiratory tract was followed. Preliminary experiences were done to assure a correct performance of the neuraminidase-inhibition test. First of all the optimal pH and then the influence of the normal hamster serum on the enzyme activity were evaluated. The n.i.a. as well as h.i.a. and anti-S and anti-V c.f.a. were demonstrable from day 6th after infection, neutralizing antibody from 8th day. The n.i.a. reached the peak of 24 days, that is later than the other types of antibodies, and started to decline after 1 month, together with the drop of the h.i.a and c.f.a. On the contrary the neutralizing antibody persisted at high titres till the end of the observation period (75 days). Detectable antibody response was coincidental with a marked drop in the titers of virus recovered from the respiratory tract. Because of the association of both hemagglutinating and neuraminidase activities with the same Sendai glycoprotein, it is stressed the possibility that hemagglutination-inhibition and neutraminidase-inibition tests titrate the same antibody."} {"id": "PMID:180922", "title": "[The inhibitory effect of alkyl-aryl-sulfonate on the swarming of proteus bacteria].", "content": "Tests were carried out on 16 strains of Proteus to determine the smallest amount of alkylarylsulfone that prevents complete swarming of the bacteria, restricting it to band only 1-2 mm wide. This was achieved by adding 0.0075% of detergent to Gassner's medium. The result was easily visible on the surface of inoculated plates. It was also shown that this inhibitory effect on the flagellar apparatus of Proteus and also Salmonella was purely temporary being due to a reversible reduction of this apparatus.", "contents": "[The inhibitory effect of alkyl-aryl-sulfonate on the swarming of proteus bacteria]. Tests were carried out on 16 strains of Proteus to determine the smallest amount of alkylarylsulfone that prevents complete swarming of the bacteria, restricting it to band only 1-2 mm wide. This was achieved by adding 0.0075% of detergent to Gassner's medium. The result was easily visible on the surface of inoculated plates. It was also shown that this inhibitory effect on the flagellar apparatus of Proteus and also Salmonella was purely temporary being due to a reversible reduction of this apparatus."} {"id": "PMID:180923", "title": "Immunization against mucosal disease--bovine viral Diarrhea (MD-BVD) in calves applying lapinized vaccine against swine fever and a modified live virus of MD-BVD.", "content": "Calves vaccinated with the modified strain C24V react by creating neutralizing antibodies in high titres and are resistent to infection while non-immunized calves manifest the clinical symptoms of MD-BVD. Calves, vaccinated with the lapinized strain \"K\" of the SF virus react by creating neutralizing antibodies in low titres against the vius of MD-BVD and manifest no apparent clinical symptoms after challenge with the virulent strain MD-BVD.", "contents": "Immunization against mucosal disease--bovine viral Diarrhea (MD-BVD) in calves applying lapinized vaccine against swine fever and a modified live virus of MD-BVD. Calves vaccinated with the modified strain C24V react by creating neutralizing antibodies in high titres and are resistent to infection while non-immunized calves manifest the clinical symptoms of MD-BVD. Calves, vaccinated with the lapinized strain \"K\" of the SF virus react by creating neutralizing antibodies in low titres against the vius of MD-BVD and manifest no apparent clinical symptoms after challenge with the virulent strain MD-BVD."} {"id": "PMID:180924", "title": "[The significance of CELO virus as a hatching egg contaminant with special reference to its oncogenic properties].", "content": "A group of young hamsters was injected subcutaneously in the neck region with allantoic fluid containing CELO virus. A second group received transplants of cells from tumours induced by CELO virus. Tumours developed in both groups. The latent period was shorter after transplantation than after virus inoculation. The tumours grew progressively, histologically resembling fibrosarcoma. It is recommended that hatching eggs infected with CELO virus should not be used in vaccine production.", "contents": "[The significance of CELO virus as a hatching egg contaminant with special reference to its oncogenic properties]. A group of young hamsters was injected subcutaneously in the neck region with allantoic fluid containing CELO virus. A second group received transplants of cells from tumours induced by CELO virus. Tumours developed in both groups. The latent period was shorter after transplantation than after virus inoculation. The tumours grew progressively, histologically resembling fibrosarcoma. It is recommended that hatching eggs infected with CELO virus should not be used in vaccine production."} {"id": "PMID:180926", "title": "[Immunological correlations between 2 strains of mucosal disease virus diarrhea (short report].", "content": "Cross-neutralization tests of the C24V strain and the \"Kotschmar\" strain provided evidence that the two strains are serological variants. Independenthy of quantitative serological differences, these strains had a better immunizing action in calves against a virulent strain of MD/VD virus. This virulent strain evidently formed a third serological variant, because when calves were infected with it, there was a decrease in the serological differences between antibodies. A practical conclusion is that diagnostic serological testing using only one strain is unlikely to detect all the infected animals, particularly those with low titres of antibody. In the presence of complement the neutralizing capacity of immune serum increased and, in the case of low antibody titres, serological differences between strains decreased. Therefore the complement-dependent neutralization test with at least two strains of virus is recommended for use in diagnostics.", "contents": "[Immunological correlations between 2 strains of mucosal disease virus diarrhea (short report]. Cross-neutralization tests of the C24V strain and the \"Kotschmar\" strain provided evidence that the two strains are serological variants. Independenthy of quantitative serological differences, these strains had a better immunizing action in calves against a virulent strain of MD/VD virus. This virulent strain evidently formed a third serological variant, because when calves were infected with it, there was a decrease in the serological differences between antibodies. A practical conclusion is that diagnostic serological testing using only one strain is unlikely to detect all the infected animals, particularly those with low titres of antibody. In the presence of complement the neutralizing capacity of immune serum increased and, in the case of low antibody titres, serological differences between strains decreased. Therefore the complement-dependent neutralization test with at least two strains of virus is recommended for use in diagnostics."} {"id": "PMID:180927", "title": "[Isolation of reoviruses from mink].", "content": "In this first report of the isolation of reovirus from mink, isolates were obtained from 18 to 26 young mink with viral enteritis, by using cultures of cat kidney cells. The isolated also produced cytopathic changes in cell cultures of mink kidney, dog kidney, piglet kidney, calf kidney, bovine embryonic kidney and calf testis. A characteristic feature was the formation of eosinophilic inclusion bodies in the cytoplasma of culture cells. Haemagglutination tests were negative with erythrocytes from cat, rabbit, pig, horse and cattle. Attempts to infect old and young mink, kittens and ferrets with tissue culture material failed. It was not known to what extent this second infection with reovirus influenced the course of mink viral enteritis.", "contents": "[Isolation of reoviruses from mink]. In this first report of the isolation of reovirus from mink, isolates were obtained from 18 to 26 young mink with viral enteritis, by using cultures of cat kidney cells. The isolated also produced cytopathic changes in cell cultures of mink kidney, dog kidney, piglet kidney, calf kidney, bovine embryonic kidney and calf testis. A characteristic feature was the formation of eosinophilic inclusion bodies in the cytoplasma of culture cells. Haemagglutination tests were negative with erythrocytes from cat, rabbit, pig, horse and cattle. Attempts to infect old and young mink, kittens and ferrets with tissue culture material failed. It was not known to what extent this second infection with reovirus influenced the course of mink viral enteritis."} {"id": "PMID:180928", "title": "The development of criteria for evaluating psychiatric education programs.", "content": "During the last year, the Psychiatry Education Branch of the National Institute of Mental Health undertook an exhaustive review of 530 training proposals from 205 institutions. The scope of such an endeavor, as well as the desire to maintain peer review, necessitated the recruitment of 90 outside consultants. The need for consistency of judgment among a large group of site visitors gave rise to a document that detailed points of concern in the evaluation of psychiatric training programs. Broader dissemination of this document might be useful in a program's self-evaluation, and might further its understanding of the site-visit process. The result of many such evaluations should be the improvement of psychiatric education throughout the country.", "contents": "The development of criteria for evaluating psychiatric education programs. During the last year, the Psychiatry Education Branch of the National Institute of Mental Health undertook an exhaustive review of 530 training proposals from 205 institutions. The scope of such an endeavor, as well as the desire to maintain peer review, necessitated the recruitment of 90 outside consultants. The need for consistency of judgment among a large group of site visitors gave rise to a document that detailed points of concern in the evaluation of psychiatric training programs. Broader dissemination of this document might be useful in a program's self-evaluation, and might further its understanding of the site-visit process. The result of many such evaluations should be the improvement of psychiatric education throughout the country."} {"id": "PMID:180929", "title": "Congenital insulinoma (nesidioblastoma): ultrastructural evidence for histogenesis from pancreatic ductal epithelium.", "content": "An insulinoma removed from a neonate with proved hyperinsulinemia was examined with the electron microscope. The tumor was composed of pancreatic ductal epithelium and beta cells in direct contact and in lobular units. The pattern of the tumor, the morphologic evidence of beta cell-type activity in ductal cells, and the similarity of the arrangement of tumor cells to that observed in islet regeneration after subtotal pancreatectomy in the rat indicate that this tumor originated from ductal epithelium.", "contents": "Congenital insulinoma (nesidioblastoma): ultrastructural evidence for histogenesis from pancreatic ductal epithelium. An insulinoma removed from a neonate with proved hyperinsulinemia was examined with the electron microscope. The tumor was composed of pancreatic ductal epithelium and beta cells in direct contact and in lobular units. The pattern of the tumor, the morphologic evidence of beta cell-type activity in ductal cells, and the similarity of the arrangement of tumor cells to that observed in islet regeneration after subtotal pancreatectomy in the rat indicate that this tumor originated from ductal epithelium."} {"id": "PMID:180930", "title": "Necrotizing retinopathy with herpes zoster ophthalmicus: a light and electron microscopical study.", "content": "A necrotizing retinopathy following a vesicular cutaneous eruption in the distribution of the right trigeminal nerve developed in a patient who had been receiving systemic corticosteroid therapy one week prior to the onset of herpes zoster ophthalmicus. Seven weeks after the herpetic symptoms began, the patient died of pneumonia following an intracerebral hematoma. At postmortem examination, unexpected multiple focal and confluent lesions, which corresponded to areas of extensive retinal necrosis, were observed in the fundus of the right eye. Intranuclear inclusions with a perinuclear halo were identified within the affected sensory retina. Electron microscopy of the retinal lesions disclosed round to oval enveloped viral particles that were characteristic of the herpes viruses. A mild lymphocytic infiltrate was evident in a demyelinated right Gasserian ganglion. Demyelination and necrosis of the right trigeminal sensory tract and adjacent areas were evident within the brain stem.", "contents": "Necrotizing retinopathy with herpes zoster ophthalmicus: a light and electron microscopical study. A necrotizing retinopathy following a vesicular cutaneous eruption in the distribution of the right trigeminal nerve developed in a patient who had been receiving systemic corticosteroid therapy one week prior to the onset of herpes zoster ophthalmicus. Seven weeks after the herpetic symptoms began, the patient died of pneumonia following an intracerebral hematoma. At postmortem examination, unexpected multiple focal and confluent lesions, which corresponded to areas of extensive retinal necrosis, were observed in the fundus of the right eye. Intranuclear inclusions with a perinuclear halo were identified within the affected sensory retina. Electron microscopy of the retinal lesions disclosed round to oval enveloped viral particles that were characteristic of the herpes viruses. A mild lymphocytic infiltrate was evident in a demyelinated right Gasserian ganglion. Demyelination and necrosis of the right trigeminal sensory tract and adjacent areas were evident within the brain stem."} {"id": "PMID:180931", "title": "Discharge planning in an acute hospital.", "content": "To improve discharge planning on an acute medical ward, a nursing \"team system\" was initiated with clear delineation of responsibility for discharge planning. The head nurse supervised the nurses' actions and supported their communication with attending physicians. To assess the efficacy of this approach, chart reviews and interviews of 60 consecutive patients were performed before and after the implementation of the plan. A plan was labeled adequate if the following criteria were met: all treatable diagnoses were recognized; appropriate treatment regimens were instituted for each diagnosis; the patient's abilities were sufficient for him to function in the proposed environment; and plans were made for follow-up care. Patient knowledge was stated to be adequate if the patient was aware of his diagnosis, treatment regimen and plans for follow-up care. In addition, the patient was questioned concerning his satisfaction with the plans for further care. Seventy-five percent of the patients admitted to this ward required discharge planning. Of those requiring discharge planning, the plan was judged adequate in 55% prior to the program change and in 83% following that change. Eighty percent of the patients required some teaching during their hospital stay. Of these, by the time of discharge, knowledge was adequate in 53% prior to the program change and 51% subsequent to the change. Initially 68% of the patients were very satisfied with the discharge plans but this figure rose to 86% following the program change.", "contents": "Discharge planning in an acute hospital. To improve discharge planning on an acute medical ward, a nursing \"team system\" was initiated with clear delineation of responsibility for discharge planning. The head nurse supervised the nurses' actions and supported their communication with attending physicians. To assess the efficacy of this approach, chart reviews and interviews of 60 consecutive patients were performed before and after the implementation of the plan. A plan was labeled adequate if the following criteria were met: all treatable diagnoses were recognized; appropriate treatment regimens were instituted for each diagnosis; the patient's abilities were sufficient for him to function in the proposed environment; and plans were made for follow-up care. Patient knowledge was stated to be adequate if the patient was aware of his diagnosis, treatment regimen and plans for follow-up care. In addition, the patient was questioned concerning his satisfaction with the plans for further care. Seventy-five percent of the patients admitted to this ward required discharge planning. Of those requiring discharge planning, the plan was judged adequate in 55% prior to the program change and in 83% following that change. Eighty percent of the patients required some teaching during their hospital stay. Of these, by the time of discharge, knowledge was adequate in 53% prior to the program change and 51% subsequent to the change. Initially 68% of the patients were very satisfied with the discharge plans but this figure rose to 86% following the program change."} {"id": "PMID:180932", "title": "Benign hepatic tumors and their association with oral contraceptives.", "content": "The growing number of reports of benign hepatic tumors occurring in young women who have been receiving oral contraceptive steroids has led us to review the 33 patients reported in the literature and to cite two additional case reports. By presenting two reports, one describing focal nodular hyperplasia and the other multiple hepatic cell adenomas, we hope to emphasize the pathological differentiation between these two lesions in order to calrify further reporting. Twelve of the 35 patients had massive intraperitoneal bleeding; two other patients had less severe hemoperitoneum. Five deaths have been reported. Although the frequency of use of these agents has become such that a direct relationship between them and benign hepatic tumors is not proved, the clinician should bear the association in mind when presented with women taking oral contraceptives who have abdominal pain. The review is made in the hope of stimulation further case reporting and microscopical and ultrastructural analysis. We trust that three will clarify the possible role of contraceptive steroids as predisposing or etiologic agents.", "contents": "Benign hepatic tumors and their association with oral contraceptives. The growing number of reports of benign hepatic tumors occurring in young women who have been receiving oral contraceptive steroids has led us to review the 33 patients reported in the literature and to cite two additional case reports. By presenting two reports, one describing focal nodular hyperplasia and the other multiple hepatic cell adenomas, we hope to emphasize the pathological differentiation between these two lesions in order to calrify further reporting. Twelve of the 35 patients had massive intraperitoneal bleeding; two other patients had less severe hemoperitoneum. Five deaths have been reported. Although the frequency of use of these agents has become such that a direct relationship between them and benign hepatic tumors is not proved, the clinician should bear the association in mind when presented with women taking oral contraceptives who have abdominal pain. The review is made in the hope of stimulation further case reporting and microscopical and ultrastructural analysis. We trust that three will clarify the possible role of contraceptive steroids as predisposing or etiologic agents."} {"id": "PMID:180933", "title": "Histocompatibility types and viral antibodies.", "content": "Serum neutralizing (Nt) antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and histocompatibility (HL-A) types, were determined in multiple sclerosis (MS) patients and in control subjects. Titers of Nt antibodies to HSV-1 and to HSV-2 were increased among subjects bearing HL-A3 or HL-A7 or both, whether they suffered from MS or not. The increases were statistically significant in the MS group. The MS and control groups did not differ significantly in levels of HSV-1 or HSV-2 Nt antibodies.", "contents": "Histocompatibility types and viral antibodies. Serum neutralizing (Nt) antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and histocompatibility (HL-A) types, were determined in multiple sclerosis (MS) patients and in control subjects. Titers of Nt antibodies to HSV-1 and to HSV-2 were increased among subjects bearing HL-A3 or HL-A7 or both, whether they suffered from MS or not. The increases were statistically significant in the MS group. The MS and control groups did not differ significantly in levels of HSV-1 or HSV-2 Nt antibodies."} {"id": "PMID:180934", "title": "Prophylactic effects of phenytoin, phenobarbital, and carbamazepine examined in kindling cat preparations.", "content": "Prophylactic effects of phenobarbital, phenytoin (diphenylhydantoin), and carbamazepine were examined in amygdaloid kindling preparations in cats. Daily electrical stimulation was delivered at the time of peak plasma levels. Comparative examination of the chronological pattern of the clinical seizure development, after discharge growth, and formation of distant independent spike foci was made between periods of kindling with chronic drug administration and of rekindling without drugs. Both phenobarbital and carbamazepine were effective, but phenytoin was totally ineffective. Prophylactic action of phenobarbital and carbamazepine was mainly through the suppression of the development of motor seizures manifestations in the former and the same with the development of sustained after discharge in the latter. The kindling preparation appears to possess many desirable features as an ideal model of human epilepsy for the purpose of assessment and recruitment of potential antiepileptic drugs and development of a rational pharmacotherapeutic approach for the management and prevention of seizure disorder.", "contents": "Prophylactic effects of phenytoin, phenobarbital, and carbamazepine examined in kindling cat preparations. Prophylactic effects of phenobarbital, phenytoin (diphenylhydantoin), and carbamazepine were examined in amygdaloid kindling preparations in cats. Daily electrical stimulation was delivered at the time of peak plasma levels. Comparative examination of the chronological pattern of the clinical seizure development, after discharge growth, and formation of distant independent spike foci was made between periods of kindling with chronic drug administration and of rekindling without drugs. Both phenobarbital and carbamazepine were effective, but phenytoin was totally ineffective. Prophylactic action of phenobarbital and carbamazepine was mainly through the suppression of the development of motor seizures manifestations in the former and the same with the development of sustained after discharge in the latter. The kindling preparation appears to possess many desirable features as an ideal model of human epilepsy for the purpose of assessment and recruitment of potential antiepileptic drugs and development of a rational pharmacotherapeutic approach for the management and prevention of seizure disorder."} {"id": "PMID:180935", "title": "Experimental herpes simplex virus encephalitis. Effect of corticosteroids and pyrimidine nucleoside.", "content": "The effects of methylprednisolone sodium succinate and cytarabine have been examined in an experimental herpes simplex virus-induced encephalitis in rabbits. In this model herpes simplex virus (HSV) is normally cleared from the brains of untreated animals. Infected animals treated with large doses of methylprednisolone showed a slight delay in the rate of clearance of virus, and a minimal reduction in the inflammatory process, but did not otherwise differ from untreated controls. Animals treated with cytarabine displayed a notable rise in viral titers in brain at a time when virus had been cleared from untreated controls. Cytarabine-treated animals also showed persistence of intranuclear inclusions in the lesions, and moderate diminution in the extent of inflammatory response. Thus, while methylprednisolone appears to have little adverse effect on the encephalitic process, cytarabine, perhaps because of its immunosuppressive properties, results in a failure of normal clearance of virus from nervous system lesions.", "contents": "Experimental herpes simplex virus encephalitis. Effect of corticosteroids and pyrimidine nucleoside. The effects of methylprednisolone sodium succinate and cytarabine have been examined in an experimental herpes simplex virus-induced encephalitis in rabbits. In this model herpes simplex virus (HSV) is normally cleared from the brains of untreated animals. Infected animals treated with large doses of methylprednisolone showed a slight delay in the rate of clearance of virus, and a minimal reduction in the inflammatory process, but did not otherwise differ from untreated controls. Animals treated with cytarabine displayed a notable rise in viral titers in brain at a time when virus had been cleared from untreated controls. Cytarabine-treated animals also showed persistence of intranuclear inclusions in the lesions, and moderate diminution in the extent of inflammatory response. Thus, while methylprednisolone appears to have little adverse effect on the encephalitic process, cytarabine, perhaps because of its immunosuppressive properties, results in a failure of normal clearance of virus from nervous system lesions."} {"id": "PMID:180936", "title": "Neuromuscular disorder associated with a defect in mitochondrial energy supply.", "content": "A limb muscle biopsy specimen from a patient with a slowly progressive congenital neuromuscular disorder disclosed, by electron microscopy, widespread mitochondrial crystalline inclusions. Biochemical studies of isolated mitochondria showed decreased respiratory rate and respiratory control with both nicotine adenine dinucleotide and flavor-protein-linked substrates. Mitochondrial adenosine triphosphatase (ATPase) activity, both basal and magnesium (Mg++) or 2,4-dinitrophenol- (DNP) stimulated, was greatly reduced in contrast to normal. The rate and extent of mitochondrial calcium accumulation was normal. These findings are consistent with a defect of the respiratory chain-linked energy transfer at a level common to all three energy coupling sites of the respiratory chain. The defect in ATPase activity may be secondary to replacement of functional mitochondrial inner membrane by crystalline inclusions.", "contents": "Neuromuscular disorder associated with a defect in mitochondrial energy supply. A limb muscle biopsy specimen from a patient with a slowly progressive congenital neuromuscular disorder disclosed, by electron microscopy, widespread mitochondrial crystalline inclusions. Biochemical studies of isolated mitochondria showed decreased respiratory rate and respiratory control with both nicotine adenine dinucleotide and flavor-protein-linked substrates. Mitochondrial adenosine triphosphatase (ATPase) activity, both basal and magnesium (Mg++) or 2,4-dinitrophenol- (DNP) stimulated, was greatly reduced in contrast to normal. The rate and extent of mitochondrial calcium accumulation was normal. These findings are consistent with a defect of the respiratory chain-linked energy transfer at a level common to all three energy coupling sites of the respiratory chain. The defect in ATPase activity may be secondary to replacement of functional mitochondrial inner membrane by crystalline inclusions."} {"id": "PMID:180937", "title": "Biochemical abnormalities of erythrocyte membranes in Duchenne dystrophy. Adenosine triphosphatase and adenyl cyclase.", "content": "Adenosine triphosphatase (ATPase) activity in erythrocyte membranes from patients with Duchenne dystrophy was inhibited by ouabain less than in normal individuals in assay systems containing high or low contents of salt. Epinephrine and cyclic adenosine monophosphate increased total ATPase activity in all samples, and epinephrine restored ouabain sensitivity to the Duchenne membranes. Basal adenyl cyclase activity in about twice that of controls. Epinephrine stimulated adenyl cyclase activity of normal membranes two to three times, but did not stimulate the enzyme in Duchenne membranes. These differences may reflect a genetic abnormality of the membrane.", "contents": "Biochemical abnormalities of erythrocyte membranes in Duchenne dystrophy. Adenosine triphosphatase and adenyl cyclase. Adenosine triphosphatase (ATPase) activity in erythrocyte membranes from patients with Duchenne dystrophy was inhibited by ouabain less than in normal individuals in assay systems containing high or low contents of salt. Epinephrine and cyclic adenosine monophosphate increased total ATPase activity in all samples, and epinephrine restored ouabain sensitivity to the Duchenne membranes. Basal adenyl cyclase activity in about twice that of controls. Epinephrine stimulated adenyl cyclase activity of normal membranes two to three times, but did not stimulate the enzyme in Duchenne membranes. These differences may reflect a genetic abnormality of the membrane."} {"id": "PMID:180938", "title": "Treatment of malignant glioma. A controlled study of chemotherapy and irradiation.", "content": "Thirty-three patients with malignant glioma were randomly divided into two groups after extensive tumor resection. Those in group A received, every five to eight weeks, a course of chemotherapy consisting of intravenously administered carmustine, 80 mg/sq m/day for three days, and vincristine sulfate, 1.4mg/sq m on days 1 and 8. Patients in group B were treated identically and received radiation therapy (RT) as well, 4,500 rads whole brain plus 1,500 rads to the side of the tumor. The median survival time of group A was 30 weeks, while that of group B was 44.5 weeks, but the overall survival curves were not significantly different. The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy. Estimates of the quality of survival suggested (1) the two groups were not comparable following randomization, possibly influencing the results; and (2) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients' conditions remain stable or improve.", "contents": "Treatment of malignant glioma. A controlled study of chemotherapy and irradiation. Thirty-three patients with malignant glioma were randomly divided into two groups after extensive tumor resection. Those in group A received, every five to eight weeks, a course of chemotherapy consisting of intravenously administered carmustine, 80 mg/sq m/day for three days, and vincristine sulfate, 1.4mg/sq m on days 1 and 8. Patients in group B were treated identically and received radiation therapy (RT) as well, 4,500 rads whole brain plus 1,500 rads to the side of the tumor. The median survival time of group A was 30 weeks, while that of group B was 44.5 weeks, but the overall survival curves were not significantly different. The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy. Estimates of the quality of survival suggested (1) the two groups were not comparable following randomization, possibly influencing the results; and (2) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients' conditions remain stable or improve."} {"id": "PMID:180940", "title": "[Primary hyperoxaluria. Clinical, histological and crystallographic study of the ocular lesions].", "content": "A post-mortem histological examination of the eyes of a case of primary hyperoxaluria revealed the presence of crystals in the ciliary processes and at the level of the retinal pigment epithelium. The crystallography study demonstrated that it consisted of wewhellite. The ocular lesions are compared with those found by other authors in primary hyperoxaluria, after prolonged methoxyflurane anaesthesia, after experimental administration of dibutyloxalic acid or naphthalene, and in the human retina in longstanding detachments. Most of the factors which give rise to the presence in the eye of oxalate and its selective precipitation in the midst of certain ocular tissues remain hypothetical. The retinal lesions observed in primary hyperoxaluria appear to be pathognomonic for hyperoxalaemia.", "contents": "[Primary hyperoxaluria. Clinical, histological and crystallographic study of the ocular lesions]. A post-mortem histological examination of the eyes of a case of primary hyperoxaluria revealed the presence of crystals in the ciliary processes and at the level of the retinal pigment epithelium. The crystallography study demonstrated that it consisted of wewhellite. The ocular lesions are compared with those found by other authors in primary hyperoxaluria, after prolonged methoxyflurane anaesthesia, after experimental administration of dibutyloxalic acid or naphthalene, and in the human retina in longstanding detachments. Most of the factors which give rise to the presence in the eye of oxalate and its selective precipitation in the midst of certain ocular tissues remain hypothetical. The retinal lesions observed in primary hyperoxaluria appear to be pathognomonic for hyperoxalaemia."} {"id": "PMID:180942", "title": "Herpes simplex virus types 1 and 2: therapeutic response to antiviral drugs.", "content": "In vitro studies have demonstrated a relative resistance of herpes simplex virus type 2 to antiviral therapy when compared with herpes simplex virus type 1. The in vivo studies, however, show an excellent therapeutic response to both antiviral drugs in experimentally induced viral keratoconjunctivitis.", "contents": "Herpes simplex virus types 1 and 2: therapeutic response to antiviral drugs. In vitro studies have demonstrated a relative resistance of herpes simplex virus type 2 to antiviral therapy when compared with herpes simplex virus type 1. The in vivo studies, however, show an excellent therapeutic response to both antiviral drugs in experimentally induced viral keratoconjunctivitis."} {"id": "PMID:180943", "title": "The Richner-Hanhart syndrome: report of a case with associated tyrosinemia.", "content": "The Richner-Hanhart syndrome with tyrosinemia was recognized in a mentally retarded adolescent boy. The clinical manifestations, including hyperkeratosis of the volar aspects of the hands and feet, thickening of the conjunctival epithelium, and corneal opacities, as well as biochemical aberrations of tyrosine metabolism, responded to specific treatment with a diet low in phenylalanine and tyrosine. Light and electron microscopical studies illustrate the underlying conjunctival pathologic changes.", "contents": "The Richner-Hanhart syndrome: report of a case with associated tyrosinemia. The Richner-Hanhart syndrome with tyrosinemia was recognized in a mentally retarded adolescent boy. The clinical manifestations, including hyperkeratosis of the volar aspects of the hands and feet, thickening of the conjunctival epithelium, and corneal opacities, as well as biochemical aberrations of tyrosine metabolism, responded to specific treatment with a diet low in phenylalanine and tyrosine. Light and electron microscopical studies illustrate the underlying conjunctival pathologic changes."} {"id": "PMID:180944", "title": "Malignant optic glioma in a 70-year-old patient.", "content": "In a 70-year-old man with glioma of the optic nerves and tracts, the initial symptom was a unilateral loss of vision that progressed rapidly and was followed by amaurosis of both eyes. All diagnostic radiological procedures were negative. Four months after the onset of the disease, the patient developed hemiplegia, became comatose, and died. Post-mortem examination revealed a glioblastoma multiforme of both optic nerves, chiasma, and optic tracts that extended posteriorly into the left thalamus and medial geniculate body. The tumoral thickening of the optic nerves was absent in the intracanalicular part, a finding that concurred with the normal radiological appearance of the optic foramen. Glioblastoma multiforme of the optic pathways should be included in the differential diagnosis of acute visual failure in elderly people, even though the final diagnosis may be possible only at postmortem examination.", "contents": "Malignant optic glioma in a 70-year-old patient. In a 70-year-old man with glioma of the optic nerves and tracts, the initial symptom was a unilateral loss of vision that progressed rapidly and was followed by amaurosis of both eyes. All diagnostic radiological procedures were negative. Four months after the onset of the disease, the patient developed hemiplegia, became comatose, and died. Post-mortem examination revealed a glioblastoma multiforme of both optic nerves, chiasma, and optic tracts that extended posteriorly into the left thalamus and medial geniculate body. The tumoral thickening of the optic nerves was absent in the intracanalicular part, a finding that concurred with the normal radiological appearance of the optic foramen. Glioblastoma multiforme of the optic pathways should be included in the differential diagnosis of acute visual failure in elderly people, even though the final diagnosis may be possible only at postmortem examination."} {"id": "PMID:180946", "title": "In defense of SISIs. The short increment sensitivity index.", "content": "We review the Short Increment Sensitivity Index (SISI) in terms of its performance with a variety of sites of lesion and its likely physiologic basis. We conclude that its original schema can be broadened to extend its clinical application if changes are made in the parameters of its routine use. The two major changes involve (1) a presentation level of no less than 90 dB hearing threshold level (HTL) and (2) a bimodal interpretation of results based on the premise that high scores indicate normal cochlear function and low scores indicate extensive cochlear damage or neural dysfunction. We suggest that routine use of the modifications suggested here can provide useful diagnostic information and bring to light a group of neurally impaired patients that has been relatively ignored.", "contents": "In defense of SISIs. The short increment sensitivity index. We review the Short Increment Sensitivity Index (SISI) in terms of its performance with a variety of sites of lesion and its likely physiologic basis. We conclude that its original schema can be broadened to extend its clinical application if changes are made in the parameters of its routine use. The two major changes involve (1) a presentation level of no less than 90 dB hearing threshold level (HTL) and (2) a bimodal interpretation of results based on the premise that high scores indicate normal cochlear function and low scores indicate extensive cochlear damage or neural dysfunction. We suggest that routine use of the modifications suggested here can provide useful diagnostic information and bring to light a group of neurally impaired patients that has been relatively ignored."} {"id": "PMID:180947", "title": "Thalidomide anomalies of the ear.", "content": "Eighteen 12- to 16-year-old patients with thalidomide embryopathy were examined otologically and neurotologically to clarify both morphological and functional ear anomalies. Ear anomalies were found in the external, middle, and inner ears. However, the inner ear, especially the vestibular portion of the labyrinth, was more extensively undeveloped both morphologically and functionally. Dysfunctions were concomitant in the oculomotor and the vestibular systems.", "contents": "Thalidomide anomalies of the ear. Eighteen 12- to 16-year-old patients with thalidomide embryopathy were examined otologically and neurotologically to clarify both morphological and functional ear anomalies. Ear anomalies were found in the external, middle, and inner ears. However, the inner ear, especially the vestibular portion of the labyrinth, was more extensively undeveloped both morphologically and functionally. Dysfunctions were concomitant in the oculomotor and the vestibular systems."} {"id": "PMID:180948", "title": "Evidence for recombination between two different immunological types of foot-and-mouth disease virus.", "content": "Recombination was observed between temperature-sensitive (ts) mutants of two immunological types of foot-and-mouth disease virus which were distinguishable by two marker characteristics in addition to their antigenic type. Putative ts+ recombinants were isolated and the segregation patterns of their marker characteristics examined. The results are discussed in terms of the origin of new sub-type strains.", "contents": "Evidence for recombination between two different immunological types of foot-and-mouth disease virus. Recombination was observed between temperature-sensitive (ts) mutants of two immunological types of foot-and-mouth disease virus which were distinguishable by two marker characteristics in addition to their antigenic type. Putative ts+ recombinants were isolated and the segregation patterns of their marker characteristics examined. The results are discussed in terms of the origin of new sub-type strains."} {"id": "PMID:180949", "title": "Coppr deficiency in the rat. Relationship to chronic cyanide poisoning.", "content": "Daily administration of increasing doses intraperitoneally of 2.5-4.0 mg NaCN/kg to male Wistar rats for 5 weeks produced acute signs of poisoning immediately post-injection but no sign of chronic toxicity except lower final body weights than in control rats. CN-treated rats had less liver copper than controls, but not below the range of normality, and their liver mitochondrial membranes were 24% less able to bind adenine nucleotides than control membranes. No other biochemical or pathological sign of copper deficiency occurred. Liver cytochrome oxidase activity was normal after the 5 weeks of CN-administration, as was the ability of liver mitochondria to synthesize phospholipids. The ultrastructure of hepatocytes was normal without evidence of the enlarged, misshapen mitochondria produced by copper deficiency. Normal cytochrome oxidase activity of liver mitochondria, together with reduced liver copper levels and reduced binding affinity of mitochondrial membranes for adenine nucleotides, indicate that the membrane binding site for adenine nucleotides is not cytochrome oxidase per se but may involve copper, perhaps by virtue of its cationicity. With repeated exposure to CN- rats develop tolerance to acute poisoning. It is suggested that this may be due to the switch in glucose catabolism towards the pentose pathway at the expense of other pathways.", "contents": "Coppr deficiency in the rat. Relationship to chronic cyanide poisoning. Daily administration of increasing doses intraperitoneally of 2.5-4.0 mg NaCN/kg to male Wistar rats for 5 weeks produced acute signs of poisoning immediately post-injection but no sign of chronic toxicity except lower final body weights than in control rats. CN-treated rats had less liver copper than controls, but not below the range of normality, and their liver mitochondrial membranes were 24% less able to bind adenine nucleotides than control membranes. No other biochemical or pathological sign of copper deficiency occurred. Liver cytochrome oxidase activity was normal after the 5 weeks of CN-administration, as was the ability of liver mitochondria to synthesize phospholipids. The ultrastructure of hepatocytes was normal without evidence of the enlarged, misshapen mitochondria produced by copper deficiency. Normal cytochrome oxidase activity of liver mitochondria, together with reduced liver copper levels and reduced binding affinity of mitochondrial membranes for adenine nucleotides, indicate that the membrane binding site for adenine nucleotides is not cytochrome oxidase per se but may involve copper, perhaps by virtue of its cationicity. With repeated exposure to CN- rats develop tolerance to acute poisoning. It is suggested that this may be due to the switch in glucose catabolism towards the pentose pathway at the expense of other pathways."} {"id": "PMID:180950", "title": "The role of calcium binding protein in the mechanism of action of cholecalciferol (vitamin D3).", "content": "A role has been sought for the calcium binding protein (CaBP) which is synthesised de novo after giving cholecalciferol (CC, vitamin D3) to rachitic chicks. After homogenation of mucosal cells in sucrose media, the CaBP was found in the 78,000 X g supernatant. Therefore, the CaBP is either present in the cytoplasm or in some labile membrane structure, e.g. the microvilli, that is disrupted by homogenation. This intracellular CaBP may facilitate diffusion of Ca into intestinal cells. No secretion of CaBP into the lumen could be detected nor did excess CaBP placed in the lumen increase Ca absorption of rachitic chicks. The mitochondria of duodenal mucosal cells contained most of the Ca being translocated by the small intestine. CaBP caused release of Ca already present in mitochondria and diminished Ca uptake by mitochondria and it appreared to do this by increasing the rate of Ca flux across the mitochondrial membrane. This would explain the greater \"turnover\" of Ca in mucosal cells of cholecalciferol-treated chicks. These and previous findings have been used to propose a scheme for the effect of cholecalciferol on Ca transport from the small intestine.", "contents": "The role of calcium binding protein in the mechanism of action of cholecalciferol (vitamin D3). A role has been sought for the calcium binding protein (CaBP) which is synthesised de novo after giving cholecalciferol (CC, vitamin D3) to rachitic chicks. After homogenation of mucosal cells in sucrose media, the CaBP was found in the 78,000 X g supernatant. Therefore, the CaBP is either present in the cytoplasm or in some labile membrane structure, e.g. the microvilli, that is disrupted by homogenation. This intracellular CaBP may facilitate diffusion of Ca into intestinal cells. No secretion of CaBP into the lumen could be detected nor did excess CaBP placed in the lumen increase Ca absorption of rachitic chicks. The mitochondria of duodenal mucosal cells contained most of the Ca being translocated by the small intestine. CaBP caused release of Ca already present in mitochondria and diminished Ca uptake by mitochondria and it appreared to do this by increasing the rate of Ca flux across the mitochondrial membrane. This would explain the greater \"turnover\" of Ca in mucosal cells of cholecalciferol-treated chicks. These and previous findings have been used to propose a scheme for the effect of cholecalciferol on Ca transport from the small intestine."} {"id": "PMID:180953", "title": "Caviation in lung cancers.", "content": "This paper examines the incidence of cavitation among tumours of the lung, the various radiological appearances and cellular types of these cavitated tumours, and the resulted of sputum cytology. Over a 46 months' period, histological and or cytological evidence of pulmonary neoplasm was found in 244 subjects whose posteroanterior chest radiographs showed opacities suggestive of pulmonary malignant disease. Of the 244 lung tumours, 220 (90%) were primary and 24 (10%) were secondary. Twenty-seven tumours (11%) were cavitated. Every cavitated tumour but one was a primary lung neoplasm. Twenty-one (81%) of these 26 cavitated primary lung tumours were squamous cell carcinoma. Large cell undifferentiated carcinoma (two cases of 7%), adenocarcinoma (one case or 4%) small cell undifferentiated carcinoma (one case or 4%) and alveolar cell carcinoma (one case or 4%) made up the rest. Sputum was examined for cells on 185 patients with primary solid and in 25 patients with primary cavitated lung cancers. Cancer cells were found in 152 patients (72%). Surprisingly, the finding of cancer cells in the sputum was no more frequent in cavitated tumours than in solid tumours. It is concluded that if a cavitated lesion in the radiograph is maglinant, a primary squamous cell carcinoma of the lung is the most likely cause. Sputum cytology performed by a competent cytologist is a very useful and simple diagnostic tool, but it appears to be no more helpful in diagnosing cavitated than in solid lung cancers.", "contents": "Caviation in lung cancers. This paper examines the incidence of cavitation among tumours of the lung, the various radiological appearances and cellular types of these cavitated tumours, and the resulted of sputum cytology. Over a 46 months' period, histological and or cytological evidence of pulmonary neoplasm was found in 244 subjects whose posteroanterior chest radiographs showed opacities suggestive of pulmonary malignant disease. Of the 244 lung tumours, 220 (90%) were primary and 24 (10%) were secondary. Twenty-seven tumours (11%) were cavitated. Every cavitated tumour but one was a primary lung neoplasm. Twenty-one (81%) of these 26 cavitated primary lung tumours were squamous cell carcinoma. Large cell undifferentiated carcinoma (two cases of 7%), adenocarcinoma (one case or 4%) small cell undifferentiated carcinoma (one case or 4%) and alveolar cell carcinoma (one case or 4%) made up the rest. Sputum was examined for cells on 185 patients with primary solid and in 25 patients with primary cavitated lung cancers. Cancer cells were found in 152 patients (72%). Surprisingly, the finding of cancer cells in the sputum was no more frequent in cavitated tumours than in solid tumours. It is concluded that if a cavitated lesion in the radiograph is maglinant, a primary squamous cell carcinoma of the lung is the most likely cause. Sputum cytology performed by a competent cytologist is a very useful and simple diagnostic tool, but it appears to be no more helpful in diagnosing cavitated than in solid lung cancers."} {"id": "PMID:180954", "title": "Plasma lipids in extra hepatic biliary obstruction.", "content": "Detailed studies of plasmsa lipids and lipoproteins were carried out on a large number of patients with proven extra hepatic biliary obstruction (EHO) to determine if changes are confined to the phospholipids and cholesterol fractions or whether the hypertriglyceridaemia, found previously in isolated studies, is present consistently and to a significant degree. Plasma lipids were also compared before and after surgical relief of the obstruction. In 15 patients with EHO (aged 16 to 78 years), compared to 23 controls (aged 18 to 63 years), there was an increase in total cholesterol due to an increase in the unesterified fraction, increase in unesterified to esterified cholesterol ratio, increase in phospholipids and increase in phospholipid to cholesterol ratio. The most striking finding was a marked and persistent elevation of triglyceride. Furthermore the increase in triglyceride was of a similar magnitude to cholesterol and phospholipid. Following relief of pbstruction the triglyceride returned to normal. The hypertriglyceridaemia in cases of EHO was associated with a clear serum and negative cold aggregation test in contrast to the changes in cases of endogenous (type IV) hypertriglyceridaemia. Hypertriglyceridaemia in EHO was associated with a broad beta fraction on the electrophoretogram. Lipoprotein-X was also detected and persisted after the relief of the obstruction despite the return of other lipid changes to normal.", "contents": "Plasma lipids in extra hepatic biliary obstruction. Detailed studies of plasmsa lipids and lipoproteins were carried out on a large number of patients with proven extra hepatic biliary obstruction (EHO) to determine if changes are confined to the phospholipids and cholesterol fractions or whether the hypertriglyceridaemia, found previously in isolated studies, is present consistently and to a significant degree. Plasma lipids were also compared before and after surgical relief of the obstruction. In 15 patients with EHO (aged 16 to 78 years), compared to 23 controls (aged 18 to 63 years), there was an increase in total cholesterol due to an increase in the unesterified fraction, increase in unesterified to esterified cholesterol ratio, increase in phospholipids and increase in phospholipid to cholesterol ratio. The most striking finding was a marked and persistent elevation of triglyceride. Furthermore the increase in triglyceride was of a similar magnitude to cholesterol and phospholipid. Following relief of pbstruction the triglyceride returned to normal. The hypertriglyceridaemia in cases of EHO was associated with a clear serum and negative cold aggregation test in contrast to the changes in cases of endogenous (type IV) hypertriglyceridaemia. Hypertriglyceridaemia in EHO was associated with a broad beta fraction on the electrophoretogram. Lipoprotein-X was also detected and persisted after the relief of the obstruction despite the return of other lipid changes to normal."} {"id": "PMID:180955", "title": "Isolation and characterisation of bovine herpesvirus mammillitis virus and its pathogenicity for cattle.", "content": "Ten viruses isolated from swabs and vesicular fluid collected from the teats of dairy cattle on 4 properties in Northern Victoria were identified as bovine herpes mammillitis (BHM) viruses by their physico-chemical and morphological properties and serological relationship to each other and a Scottish Strain of BHM virus. The viruses, isolated in bovine kidney and testicular cell cultures, produced cytopathic effects characterised by very large syncytia and eosinophilic intranuclear inculsion bodies. The intradermal inoculation of BHM virus into two cattle produced necrosis and ulceration of the skin of the teats about the area of inoculation and the development of serum neutralising antibody. After healing of the ulcers on day 37 after inoculation, the cattle were intravenously inoculated with corticosteroid for 6 days but BHM virus was not re-isolated from the teat skin or vaginal or nasal swabs.", "contents": "Isolation and characterisation of bovine herpesvirus mammillitis virus and its pathogenicity for cattle. Ten viruses isolated from swabs and vesicular fluid collected from the teats of dairy cattle on 4 properties in Northern Victoria were identified as bovine herpes mammillitis (BHM) viruses by their physico-chemical and morphological properties and serological relationship to each other and a Scottish Strain of BHM virus. The viruses, isolated in bovine kidney and testicular cell cultures, produced cytopathic effects characterised by very large syncytia and eosinophilic intranuclear inculsion bodies. The intradermal inoculation of BHM virus into two cattle produced necrosis and ulceration of the skin of the teats about the area of inoculation and the development of serum neutralising antibody. After healing of the ulcers on day 37 after inoculation, the cattle were intravenously inoculated with corticosteroid for 6 days but BHM virus was not re-isolated from the teat skin or vaginal or nasal swabs."} {"id": "PMID:180956", "title": "Bovine herpes mammillitis of dairy cattle in Victoria.", "content": "The occurrences of bovine herpes mammillitis in the Cohuna and Numurkah districts of northcentral Victoria is described. The disease was characterised by painful swollen teats, necrosis of variable areas of the teat skin, formation of blue-black scabs which sloughed leaving ulcers which were slow to heal. The outbreaks occurred during tspring months of October to mid-December when as many as 90% of milking cows in herds became infected. Epidemiologically the infection behaved as though it was transmitted by insects but proof of insect transmission was not attempted.", "contents": "Bovine herpes mammillitis of dairy cattle in Victoria. The occurrences of bovine herpes mammillitis in the Cohuna and Numurkah districts of northcentral Victoria is described. The disease was characterised by painful swollen teats, necrosis of variable areas of the teat skin, formation of blue-black scabs which sloughed leaving ulcers which were slow to heal. The outbreaks occurred during tspring months of October to mid-December when as many as 90% of milking cows in herds became infected. Epidemiologically the infection behaved as though it was transmitted by insects but proof of insect transmission was not attempted."} {"id": "PMID:180957", "title": "In vitro biological differences between the pathogenic and the apathogenic Marek's disease herpesvirus.", "content": "When three pathogenic and four apathogenic isolants of Marek's disease herpesvirus (MDHV) were compared, the pathogenic isolants differed from the apathogenic isolants in their in vitro growth and sensitivity to plaque inhibition by dextran sulfate. Plaques by the pathogenic MDHV isolants were distinctively different in their morphology from those by the apathogenic isolants, the plaque difference being most pronounced in chick embryo fibroblase (CEF) and duck embryo fibroblast (DEF) cell cultures. The pathogenic isolants formed plaques similarly in both CEF and DEF cultures, whereas the apathogenic isolants did so readily in CEF cultures, but very poorly in DEF cultures. The pathogenic isolants replicated better in DEF than in CEF cultures, whereas the apathogenic isolants replicated better in CEF than in DEF cultures. The sensitivitty to plaque inhibition by dextran sulfate was greater for the apathogenic isolants than for the pathogenic isolants of MDHV.", "contents": "In vitro biological differences between the pathogenic and the apathogenic Marek's disease herpesvirus. When three pathogenic and four apathogenic isolants of Marek's disease herpesvirus (MDHV) were compared, the pathogenic isolants differed from the apathogenic isolants in their in vitro growth and sensitivity to plaque inhibition by dextran sulfate. Plaques by the pathogenic MDHV isolants were distinctively different in their morphology from those by the apathogenic isolants, the plaque difference being most pronounced in chick embryo fibroblase (CEF) and duck embryo fibroblast (DEF) cell cultures. The pathogenic isolants formed plaques similarly in both CEF and DEF cultures, whereas the apathogenic isolants did so readily in CEF cultures, but very poorly in DEF cultures. The pathogenic isolants replicated better in DEF than in CEF cultures, whereas the apathogenic isolants replicated better in CEF than in DEF cultures. The sensitivitty to plaque inhibition by dextran sulfate was greater for the apathogenic isolants than for the pathogenic isolants of MDHV."} {"id": "PMID:180958", "title": "A possible association between plaque type and pathogenicity of Marek's disease herpesvirus.", "content": "Eighteen isolants of Marek's disease herpesvirus (MDHV) were examined for their plaque types in chicken embryo fibroblast cell cultures and their pathogenicity to an experimental line of White Leghorns highly susceptible to MD. Seven isolants (Id-1, GA, WSU-GF, and 4 field isolants) induced morphologically similar small-cell plaques (SC plaques) consisting of small round refractile cells, whereas 11 isolants (HN and 10 isolants from zoo birds) all induced large-cell plaques (LC plaques) containing large cells along with small refractile cells. The 7 SC plaque isolants all produced clinical MD with high incidences of gross MD tumors, while all 11 LC plaque isolants produced subclinical infection with only minimal histologic lesions. This observation strongly suggests a possible association between plaque type and pathogenicity of MDHV isolants.", "contents": "A possible association between plaque type and pathogenicity of Marek's disease herpesvirus. Eighteen isolants of Marek's disease herpesvirus (MDHV) were examined for their plaque types in chicken embryo fibroblast cell cultures and their pathogenicity to an experimental line of White Leghorns highly susceptible to MD. Seven isolants (Id-1, GA, WSU-GF, and 4 field isolants) induced morphologically similar small-cell plaques (SC plaques) consisting of small round refractile cells, whereas 11 isolants (HN and 10 isolants from zoo birds) all induced large-cell plaques (LC plaques) containing large cells along with small refractile cells. The 7 SC plaque isolants all produced clinical MD with high incidences of gross MD tumors, while all 11 LC plaque isolants produced subclinical infection with only minimal histologic lesions. This observation strongly suggests a possible association between plaque type and pathogenicity of MDHV isolants."} {"id": "PMID:180959", "title": "Vaccination and revaccination with a Holland (H) strain of infectious bronchitis virus.", "content": "One-day-old chickens possessing maternally derived immunity to Massachusetts-type infectious bronchitis virus (IBV) were vaccinated by the eyedrop route with a Holland (H) IBV strain of the Massachusetts type. Vaccination was done with the 72nd and 92nd passages in chicken embryos. Attenuation of the virus was done in the authors' laboratory. Four weeks postvaccination the immunity was challenged with 8 different IBV serotypes. A broad spectrum of protection from respiratory signs was obtained in each of the challenged groups (compared with unvaccinated controls). With 5 of the challenge viruses, protection against tracheal virus shed was good (70% or greater). Revaccination at 4 weeks old by the aerosol route with the 53rd and 72nd passages did not greatly enhance protection. However, the virus-serum-neutralizing (VN) titers with Massachusetts-type IBV as an indicator were high, and an anamnestic response was demonstrated at 8 weeks of age. The VN titers observed at 4 weeks old were generally low and did not correlate necessarily with the protection engendered.", "contents": "Vaccination and revaccination with a Holland (H) strain of infectious bronchitis virus. One-day-old chickens possessing maternally derived immunity to Massachusetts-type infectious bronchitis virus (IBV) were vaccinated by the eyedrop route with a Holland (H) IBV strain of the Massachusetts type. Vaccination was done with the 72nd and 92nd passages in chicken embryos. Attenuation of the virus was done in the authors' laboratory. Four weeks postvaccination the immunity was challenged with 8 different IBV serotypes. A broad spectrum of protection from respiratory signs was obtained in each of the challenged groups (compared with unvaccinated controls). With 5 of the challenge viruses, protection against tracheal virus shed was good (70% or greater). Revaccination at 4 weeks old by the aerosol route with the 53rd and 72nd passages did not greatly enhance protection. However, the virus-serum-neutralizing (VN) titers with Massachusetts-type IBV as an indicator were high, and an anamnestic response was demonstrated at 8 weeks of age. The VN titers observed at 4 weeks old were generally low and did not correlate necessarily with the protection engendered."} {"id": "PMID:180960", "title": "Strains of infectious bronchitis virus on the Delmarva peninsula and in Arkansas.", "content": "The constant-virus variable-serum neutralization test in chicken tracheal cultures was used to serotype infectious bronchitis virus (IBV) isolants from the Delmarva peninsula and Arkansas. Of 106 isolants obtained from Delmarva in 1971-1974, 93 were found to be the JMK strain, 5 Massachusetts (Mass), 5 Connecticut (Conn), 2 a new strain designated Maryland (Md) 27, and 1 a new strain designated Md 31. Of 26 isolants obtained from Arkansas between October, 1971, and February, 1973, 17 were Arkansas (Ark) 99, 4 Mass, 1 Conn, and 1 an additional new strain, designated Ark 155. Antisera produced against 2 more isolants each neutralized both Ark 99 and Mass viruses. Antiserum against another isolant neutralized both Ark 155 and Conn viruses. The neutralizing characteristics of the new strains are described.", "contents": "Strains of infectious bronchitis virus on the Delmarva peninsula and in Arkansas. The constant-virus variable-serum neutralization test in chicken tracheal cultures was used to serotype infectious bronchitis virus (IBV) isolants from the Delmarva peninsula and Arkansas. Of 106 isolants obtained from Delmarva in 1971-1974, 93 were found to be the JMK strain, 5 Massachusetts (Mass), 5 Connecticut (Conn), 2 a new strain designated Maryland (Md) 27, and 1 a new strain designated Md 31. Of 26 isolants obtained from Arkansas between October, 1971, and February, 1973, 17 were Arkansas (Ark) 99, 4 Mass, 1 Conn, and 1 an additional new strain, designated Ark 155. Antisera produced against 2 more isolants each neutralized both Ark 99 and Mass viruses. Antiserum against another isolant neutralized both Ark 155 and Conn viruses. The neutralizing characteristics of the new strains are described."} {"id": "PMID:180964", "title": "Interrelation of atmospheric ozone and cholecalciferol (vitamin D3) production in man.", "content": "Mean atmospheric ozone levels have increased steadily in the last 25 years, and this is likely to have decreased the amount of UVR reaching the earth's surface. Vitamin D3 formation in man depends on the UV irradiation of a precursor in the skin, and so we have used a computer, and the action spectrum for D3 production, to calculate the probable reduction in vitamin D3 formed by the human skin as a result of the increased ozone levels. We estimate that in the period from 1951 to 1972 the total vitamin D accumulation by the body might have thus been reduced by 15%.", "contents": "Interrelation of atmospheric ozone and cholecalciferol (vitamin D3) production in man. Mean atmospheric ozone levels have increased steadily in the last 25 years, and this is likely to have decreased the amount of UVR reaching the earth's surface. Vitamin D3 formation in man depends on the UV irradiation of a precursor in the skin, and so we have used a computer, and the action spectrum for D3 production, to calculate the probable reduction in vitamin D3 formed by the human skin as a result of the increased ozone levels. We estimate that in the period from 1951 to 1972 the total vitamin D accumulation by the body might have thus been reduced by 15%."} {"id": "PMID:180961", "title": "Emergence pattern of egg-adapted avian encephalomyelitis virus by alternating passage in chickens and embryos.", "content": "The chance of inducing complete egg-adaptation was slight in alternating passage in chickens and embryos with chicken-brain-passaged viruses of wild avian encephalomyelitis viruses: egg-adaptation was accomplished by use of an incipient egg-adapting mutant, but failed with other passaged virus.", "contents": "Emergence pattern of egg-adapted avian encephalomyelitis virus by alternating passage in chickens and embryos. The chance of inducing complete egg-adaptation was slight in alternating passage in chickens and embryos with chicken-brain-passaged viruses of wild avian encephalomyelitis viruses: egg-adaptation was accomplished by use of an incipient egg-adapting mutant, but failed with other passaged virus."} {"id": "PMID:180963", "title": "Anorexia as the probable cause of plasma alpha-lipoprotein changes seen in avian erythroblastosis.", "content": "The plasma alpha-lipoprotein bands seen on starch-gel electrophoresis are progressively split and retarded as avian erythroblastosis progresses. Similar changes may be produced in normal birds by starvation, and by pair-feeding methods. Anorexia appears to be a major cause, if not the total cause, of the plasma alpha-lipoprotein changes seen in erythroblastosis.", "contents": "Anorexia as the probable cause of plasma alpha-lipoprotein changes seen in avian erythroblastosis. The plasma alpha-lipoprotein bands seen on starch-gel electrophoresis are progressively split and retarded as avian erythroblastosis progresses. Similar changes may be produced in normal birds by starvation, and by pair-feeding methods. Anorexia appears to be a major cause, if not the total cause, of the plasma alpha-lipoprotein changes seen in erythroblastosis."} {"id": "PMID:180967", "title": "Change in the mixed function oxidase system of liver microsomes in rats treated with 3'-methyl-4-dimethylaminoazobenzene.", "content": "The mixed function oxidase systems of plasma membranes, the Golgi apparatus, and smooth and rough endoplasmic reticula of the livers of rats fed on a standard diet containing 0.06% (w/w) 3'-methyl-4-dimethylaminoazobenzene were investigated. The components and activities of the mixed function oxidase systems of the smooth endoplasmic reticulum and Golgi apparatus were especially reduced by the carcinogen. The activities for hydroxylation of anilines and demethylation of p-nitroanisole and the contents of cytochromes P-450 and b5 of the submicrosomal fractions of the rats decreased considerably more than the activities of NADH- and NADPH-ferricyanide reductases. More than 90% of the ferri-cytochrome P-450 content of the 3'-methyl-4-dimethylaminoazobenzene induced microsomes at 20 K was in the low spin form.", "contents": "Change in the mixed function oxidase system of liver microsomes in rats treated with 3'-methyl-4-dimethylaminoazobenzene. The mixed function oxidase systems of plasma membranes, the Golgi apparatus, and smooth and rough endoplasmic reticula of the livers of rats fed on a standard diet containing 0.06% (w/w) 3'-methyl-4-dimethylaminoazobenzene were investigated. The components and activities of the mixed function oxidase systems of the smooth endoplasmic reticulum and Golgi apparatus were especially reduced by the carcinogen. The activities for hydroxylation of anilines and demethylation of p-nitroanisole and the contents of cytochromes P-450 and b5 of the submicrosomal fractions of the rats decreased considerably more than the activities of NADH- and NADPH-ferricyanide reductases. More than 90% of the ferri-cytochrome P-450 content of the 3'-methyl-4-dimethylaminoazobenzene induced microsomes at 20 K was in the low spin form."} {"id": "PMID:180968", "title": "Detection of T-cell surface determinants in three Marek's disease lymphoblastoid cell lines.", "content": "The T-cell surface antigens on three lymphoblastoid cell lines, MOB1, MOB-2 and MSB-1, derived from Marek's disease lymphomas were examined by the cytotoxicity test and the indirect membrane immunofluorescent test. These cell lines reacted specifically with antisera prepared against chicken thymus cells, although their reactivities were less than that of typical thymus cells. These three cell lines were of thymus origin.", "contents": "Detection of T-cell surface determinants in three Marek's disease lymphoblastoid cell lines. The T-cell surface antigens on three lymphoblastoid cell lines, MOB1, MOB-2 and MSB-1, derived from Marek's disease lymphomas were examined by the cytotoxicity test and the indirect membrane immunofluorescent test. These cell lines reacted specifically with antisera prepared against chicken thymus cells, although their reactivities were less than that of typical thymus cells. These three cell lines were of thymus origin."} {"id": "PMID:180971", "title": "The regulation of carbamoyl phosphate synthase activity in rat liver mitochondria.", "content": "The rate at which isolated rat liver mitochondria synthesized citrulline with NH4C1 as nitrogen source was markedly dependent on the protein content of the diet. 2. Citrulline synthesis was not rate-limited by substrate concentration, substrate transport or ornithine transcarbamoylase activity under the conditions used. 3. The intramitochondrial content of an activator of carbamoyl phosphate synthase, assumed to be N-acetyl-glutamate, varied markedly with dietary protein content. The variation in the concentration of this activator was sufficient to account for the observed variation in the rates of citrulline synthesis if this synthesis were rate-limited by the activity of carbamoyl phosphate synthase. 4. The rates of urea formation from NH4Cl as nitrogen source in isolated liver cells showed variations in response to diet that closely paralleled the variations in the rates of citrulline synthesis observed in isolated mitochondria. 5. These results are consistent with the postulate that when NH4Cl plus ornithine are present in an excess, the rate of urea synthesis is regulated at the level of carbamoyl phosphate synthase activity.", "contents": "The regulation of carbamoyl phosphate synthase activity in rat liver mitochondria. The rate at which isolated rat liver mitochondria synthesized citrulline with NH4C1 as nitrogen source was markedly dependent on the protein content of the diet. 2. Citrulline synthesis was not rate-limited by substrate concentration, substrate transport or ornithine transcarbamoylase activity under the conditions used. 3. The intramitochondrial content of an activator of carbamoyl phosphate synthase, assumed to be N-acetyl-glutamate, varied markedly with dietary protein content. The variation in the concentration of this activator was sufficient to account for the observed variation in the rates of citrulline synthesis if this synthesis were rate-limited by the activity of carbamoyl phosphate synthase. 4. The rates of urea formation from NH4Cl as nitrogen source in isolated liver cells showed variations in response to diet that closely paralleled the variations in the rates of citrulline synthesis observed in isolated mitochondria. 5. These results are consistent with the postulate that when NH4Cl plus ornithine are present in an excess, the rate of urea synthesis is regulated at the level of carbamoyl phosphate synthase activity."} {"id": "PMID:180972", "title": "Kinetic characterization of the membrane-bound cytochromes of Escherichia coli grown under a variety of conditions by using a stopped-flow dual-wavelength spectrophotometer.", "content": "A study was made of the rapid oxidation kinetics of the cytochromes of Escherichia coli. The b-type cytochromes were kinetically heterogeneous, with one species (presumably cytochrome o) oxidized so rapidly that it could fully support observed oxidation rates. Cytochrome d but not cytochrome a1 was also kinetically competent to support respiration. However, in cells grown anaerobically in the presence of NO3-, cytochrome d exhibited slow oxidation kinetics and a red-shift in its reduced-minus-oxidized difference spectrum.", "contents": "Kinetic characterization of the membrane-bound cytochromes of Escherichia coli grown under a variety of conditions by using a stopped-flow dual-wavelength spectrophotometer. A study was made of the rapid oxidation kinetics of the cytochromes of Escherichia coli. The b-type cytochromes were kinetically heterogeneous, with one species (presumably cytochrome o) oxidized so rapidly that it could fully support observed oxidation rates. Cytochrome d but not cytochrome a1 was also kinetically competent to support respiration. However, in cells grown anaerobically in the presence of NO3-, cytochrome d exhibited slow oxidation kinetics and a red-shift in its reduced-minus-oxidized difference spectrum."} {"id": "PMID:180973", "title": "The structure and subunit composition of the particulate NADH-ubiquinone reductase of bovine heart mitochondria.", "content": "Preparations of NADH-ubiquinone reductase from bovine heart mitochondria (Complex I) were shown to contain at least 16 polypeptides by gel electrophoresis in the presence of sodium dodecyl sulphate. 2. High-molecular-weight soluble NADH dehydrogenase prepared from Triton X-100 extracts of submitochondrial particles [Baugh & King (1972) Biochem. Biophys. Res. Commun. 49, 1165-1173] was similar to Complex I in its polypeptide composition. 3. Solubilization of Complex I by phospholipase A treatment and subsequent sucrose-density-gradient centrifugation did not alter the polypeptide composition. 4. Lysophosphatidylcholine treatment of Complex I caused some selective solubilization of a polypeptide of mol.wt. 33000 previosuly postulated to be the transmembrane component of Complex I in the mitochondrial membrane [Ragan (1975) in Energy Transducing Membranes: Structure, Function and Reconstitution (Bennun, Bacila & Najjar, eds.), Junk, The Hague, in the press]. 5. Chaotropic resolution of Complex I caused solubilization of polypeptides of molecular weights 75000, 53000, 29000, 26000 and 15500 and traces of others in the 10000-20000-mol.wt.range. 6. The major components of the iron-protein fraction from chaotropic resolution had molecular weights of 75000, 53000 and 29000, whereas the flavoprotein contained polypeptides of molecular weights 53000 and 26000 in a 1:1 molar ratio. 7. Iodination of Complex I by lactoperoxidase indicated that the water-soluble polypeptides released by chaotropic resolution, in particular those of the flavoprotein fraction, were largely buried in the intact Complex. 8. The polypeptides of molecular weights 75000, 53000, 42000, 39000, 33000, 29000 and 26000 were present in 1:2:1:1:1:1:1 molar proportions. The two subunits of molecular weight 53000 are probably non-identical.", "contents": "The structure and subunit composition of the particulate NADH-ubiquinone reductase of bovine heart mitochondria. Preparations of NADH-ubiquinone reductase from bovine heart mitochondria (Complex I) were shown to contain at least 16 polypeptides by gel electrophoresis in the presence of sodium dodecyl sulphate. 2. High-molecular-weight soluble NADH dehydrogenase prepared from Triton X-100 extracts of submitochondrial particles [Baugh & King (1972) Biochem. Biophys. Res. Commun. 49, 1165-1173] was similar to Complex I in its polypeptide composition. 3. Solubilization of Complex I by phospholipase A treatment and subsequent sucrose-density-gradient centrifugation did not alter the polypeptide composition. 4. Lysophosphatidylcholine treatment of Complex I caused some selective solubilization of a polypeptide of mol.wt. 33000 previosuly postulated to be the transmembrane component of Complex I in the mitochondrial membrane [Ragan (1975) in Energy Transducing Membranes: Structure, Function and Reconstitution (Bennun, Bacila & Najjar, eds.), Junk, The Hague, in the press]. 5. Chaotropic resolution of Complex I caused solubilization of polypeptides of molecular weights 75000, 53000, 29000, 26000 and 15500 and traces of others in the 10000-20000-mol.wt.range. 6. The major components of the iron-protein fraction from chaotropic resolution had molecular weights of 75000, 53000 and 29000, whereas the flavoprotein contained polypeptides of molecular weights 53000 and 26000 in a 1:1 molar ratio. 7. Iodination of Complex I by lactoperoxidase indicated that the water-soluble polypeptides released by chaotropic resolution, in particular those of the flavoprotein fraction, were largely buried in the intact Complex. 8. The polypeptides of molecular weights 75000, 53000, 42000, 39000, 33000, 29000 and 26000 were present in 1:2:1:1:1:1:1 molar proportions. The two subunits of molecular weight 53000 are probably non-identical."} {"id": "PMID:180975", "title": "Regulation of enzyme turnover during tissue differentiation. Interactions of insulin, prolactin and cortisol in controlling the turnover of fatty acid synthetase in rabbit mammary gland in organ culture.", "content": "1. Explants of mammary gland from mid-pregnant rabbits were cultured in Medium 199 containing combinations of insulin, prolactin and cortisol. With hormone combinations which included prolactin, a sustained increase in the apparent rate of synthesis and in the amount of fatty acid synthetase was measurable immunologically. Maximum increase was produced with insulin, prolactin and cortisol present together. 2. With prolactin present alone, synthetase activity in the explants decreased to undetectable values after 1 day in culture, whereas the incorporation of l-[U-(14)C]leucine into immunodetectable material increased. Prolactin may therefore direct the synthesis of immunologically cross-reactive precursors of fatty acid synthetase which are enzymically inactive. 3. Culture with dibutyryl cyclic AMP plus theophylline in the presence of insulin, prolactin and cortisol delayed the increase in the rate of synthesis and accumulation of the synthetase. These compounds may also prevent the apparent decrease in the rate of degradation of the synthetase which occurs on day 2 of culture. 4. A large decrease in the apparent rate of degradation of the synthetase on day 2 of culture occurs during culture with hormone combinations which include prolactin. The protein obtained by centrifugation of explant homogenates for 6min at 14000g(av.) is degraded continuously throughout the culture period. 5. This decrease in the apparent rate of degradation of the synthetase was measured by radio-immunological precipitation. It is probably part of a regulated programme of enzyme degradation and not a reflexion of the reutilization of radioactive amino acids for the following reasons. (a) The calculated increase in the amount of the synthetase in explants on day 2 of culture with insulin, prolactin and cortisol was approximately equal to the measured increase of the enzyme complex which accumulates in the explants. This suggests little or no enzyme degradation has occurred. (b) Explants were cultured for 24h with insulin, prolactin and cortisol. They were then incubated with l-[U-(14)C]leucine, washed and incubated again for up to 4(1/2)h. l-[U-(14)C]Leucine rapidly equilibrated with the intracellular amino acid pool. Within 10min of incubation after washing explants to remove endogenous l-[U-(14)C]leucine the previously linear incorporation of l-[U-(14)C]-leucine into total explant protein ceased. This suggests that protein is synthesized from an amino acid pool which rapidly equilibrates with amino acids in the culture medium. (c) Explants were cultured for 24h as described in (b) but after washing they were cultured with insulin, prolactin and cortisol for 24h. Approx. 90% of the radioactivity lost from the ;free' intracellular amino acid pool and from amino acids derived from the degradation of explant protein in this period was detected in the culture medium. This suggests that the ;free' intracellular amino acids and amino acids derived from protein degradation can equilibrate with amino acids in the medium. A residual ;free' radioactive amino acid pool was present in the tissue. (d) Casein represents approx. 20% of the protein synthesized after 1 day in culture with insulin, prolactin and cortisol. Histological evidence suggests that on day 2 of culture, casein is unlikely to be degraded in the tissue. No increase in the radioactivity incorporated into casein can be measured in the 23h after incubation of explants with l-[U-(14)C]leucine as described in (b). This suggests that the incorporation of radioactivity into proteins during culture after incubation with l-[U-(14)C]leucine is minimal. (e) Inhibition of protein synthesis in explants by cycloheximide after incubation with l-[U-(14)C]leucine does not reveal a latent continuous degradation of fatty acid synthetase on day 2 of culture which might have been masked by the high rates of protein synthesis and therefore the accumulation of the enzyme. 6. The conclusion is discussed that there is a real decrease (or even cessation) in the rate of degradation of fatty acid synthetase during the period when the enzyme accumulates in explants cultured with hormone combinations which contain prolactin.", "contents": "Regulation of enzyme turnover during tissue differentiation. Interactions of insulin, prolactin and cortisol in controlling the turnover of fatty acid synthetase in rabbit mammary gland in organ culture. 1. Explants of mammary gland from mid-pregnant rabbits were cultured in Medium 199 containing combinations of insulin, prolactin and cortisol. With hormone combinations which included prolactin, a sustained increase in the apparent rate of synthesis and in the amount of fatty acid synthetase was measurable immunologically. Maximum increase was produced with insulin, prolactin and cortisol present together. 2. With prolactin present alone, synthetase activity in the explants decreased to undetectable values after 1 day in culture, whereas the incorporation of l-[U-(14)C]leucine into immunodetectable material increased. Prolactin may therefore direct the synthesis of immunologically cross-reactive precursors of fatty acid synthetase which are enzymically inactive. 3. Culture with dibutyryl cyclic AMP plus theophylline in the presence of insulin, prolactin and cortisol delayed the increase in the rate of synthesis and accumulation of the synthetase. These compounds may also prevent the apparent decrease in the rate of degradation of the synthetase which occurs on day 2 of culture. 4. A large decrease in the apparent rate of degradation of the synthetase on day 2 of culture occurs during culture with hormone combinations which include prolactin. The protein obtained by centrifugation of explant homogenates for 6min at 14000g(av.) is degraded continuously throughout the culture period. 5. This decrease in the apparent rate of degradation of the synthetase was measured by radio-immunological precipitation. It is probably part of a regulated programme of enzyme degradation and not a reflexion of the reutilization of radioactive amino acids for the following reasons. (a) The calculated increase in the amount of the synthetase in explants on day 2 of culture with insulin, prolactin and cortisol was approximately equal to the measured increase of the enzyme complex which accumulates in the explants. This suggests little or no enzyme degradation has occurred. (b) Explants were cultured for 24h with insulin, prolactin and cortisol. They were then incubated with l-[U-(14)C]leucine, washed and incubated again for up to 4(1/2)h. l-[U-(14)C]Leucine rapidly equilibrated with the intracellular amino acid pool. Within 10min of incubation after washing explants to remove endogenous l-[U-(14)C]leucine the previously linear incorporation of l-[U-(14)C]-leucine into total explant protein ceased. This suggests that protein is synthesized from an amino acid pool which rapidly equilibrates with amino acids in the culture medium. (c) Explants were cultured for 24h as described in (b) but after washing they were cultured with insulin, prolactin and cortisol for 24h. Approx. 90% of the radioactivity lost from the ;free' intracellular amino acid pool and from amino acids derived from the degradation of explant protein in this period was detected in the culture medium. This suggests that the ;free' intracellular amino acids and amino acids derived from protein degradation can equilibrate with amino acids in the medium. A residual ;free' radioactive amino acid pool was present in the tissue. (d) Casein represents approx. 20% of the protein synthesized after 1 day in culture with insulin, prolactin and cortisol. Histological evidence suggests that on day 2 of culture, casein is unlikely to be degraded in the tissue. No increase in the radioactivity incorporated into casein can be measured in the 23h after incubation of explants with l-[U-(14)C]leucine as described in (b). This suggests that the incorporation of radioactivity into proteins during culture after incubation with l-[U-(14)C]leucine is minimal. (e) Inhibition of protein synthesis in explants by cycloheximide after incubation with l-[U-(14)C]leucine does not reveal a latent continuous degradation of fatty acid synthetase on day 2 of culture which might have been masked by the high rates of protein synthesis and therefore the accumulation of the enzyme. 6. The conclusion is discussed that there is a real decrease (or even cessation) in the rate of degradation of fatty acid synthetase during the period when the enzyme accumulates in explants cultured with hormone combinations which contain prolactin."} {"id": "PMID:180974", "title": "Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide.", "content": "The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mM) or dichloroacetate (1mM) increased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart, presumably by inhibiting the pyruvate dehydrogenase kinase reaction. Alloxan-diabetes markedly decreased the proportion of active dehydrogenase in hearts perfused with pyruvate or dichloroacetate. 3. The total activity of pyruvate dehydrogenase in mitochondria prepared from rat heart was unchanged by diabetes. Incubation of mitochondria with 2-oxo-glutarate plus malate increased ATP and NADH concentrations and decreased the proportion of active pyruvate dehydrogenase. The decrease in active dehydrogenase was somewhat greater in mitochondria prepared from hearts of diabetic rats than in those from hearts of non-diabetic rats. Pyruvate (0.1-10 mM) or dichloroacetate (4-50 muM) increased the proportion of active dehydrogenase in isolated mitochondria presumably by inhibition of the pyruvate dehydrogenase kinase reaction. They were much less effective in mitochondria from the hearts of diabetic rats than in those of non-diabetic rats. 4. The matrix water space was increased in preparations of mitochondria from hearts of diabetic rats. Dichloroacetate was concentrated in the matrix water of mitochondria of non-diabetic rats (approx. 16-fold at 10 muM); mitochondria from hearts of diabetic rats concentrated dichloroacetate less effectively. 5. The pyruvate dehydrogenase phosphate phosphatase activity of rat hearts and of rat heart mitochondria (approx. 1-2 munit/unit of pyruvate dehydrogenase) was not affected by diabetes. 6. The rate of oxidation of [1-14C]pyruvate by rat heart mitochondria (6.85 nmol/min per mg of protein with 50 muM-pyruvate) was approx. 46% of the Vmax. value of extracted pyruvate dehydrogenase (active form). Palmitoyl-L-carnitine, which increased the ratio of [acetyl-CoA]/[CoA] 16-fold, inhibited oxidation of pyruvate by about 90% without changing the proportion of active pyruvate dehydrogenase.", "contents": "Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mM) or dichloroacetate (1mM) increased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart, presumably by inhibiting the pyruvate dehydrogenase kinase reaction. Alloxan-diabetes markedly decreased the proportion of active dehydrogenase in hearts perfused with pyruvate or dichloroacetate. 3. The total activity of pyruvate dehydrogenase in mitochondria prepared from rat heart was unchanged by diabetes. Incubation of mitochondria with 2-oxo-glutarate plus malate increased ATP and NADH concentrations and decreased the proportion of active pyruvate dehydrogenase. The decrease in active dehydrogenase was somewhat greater in mitochondria prepared from hearts of diabetic rats than in those from hearts of non-diabetic rats. Pyruvate (0.1-10 mM) or dichloroacetate (4-50 muM) increased the proportion of active dehydrogenase in isolated mitochondria presumably by inhibition of the pyruvate dehydrogenase kinase reaction. They were much less effective in mitochondria from the hearts of diabetic rats than in those of non-diabetic rats. 4. The matrix water space was increased in preparations of mitochondria from hearts of diabetic rats. Dichloroacetate was concentrated in the matrix water of mitochondria of non-diabetic rats (approx. 16-fold at 10 muM); mitochondria from hearts of diabetic rats concentrated dichloroacetate less effectively. 5. The pyruvate dehydrogenase phosphate phosphatase activity of rat hearts and of rat heart mitochondria (approx. 1-2 munit/unit of pyruvate dehydrogenase) was not affected by diabetes. 6. The rate of oxidation of [1-14C]pyruvate by rat heart mitochondria (6.85 nmol/min per mg of protein with 50 muM-pyruvate) was approx. 46% of the Vmax. value of extracted pyruvate dehydrogenase (active form). Palmitoyl-L-carnitine, which increased the ratio of [acetyl-CoA]/[CoA] 16-fold, inhibited oxidation of pyruvate by about 90% without changing the proportion of active pyruvate dehydrogenase."} {"id": "PMID:180976", "title": "Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors.", "content": "Protein kinase activity was determined in subcellular fractions of rat testis interstitial tissue after incubation of the intact tissue with LH (luteinizing hormone) in vitro. Various factors that might have changed the activity of this enzyme during preparation of the fractions before assay were also investigated. The following results were obtained. 1. LH and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor) added together during incubation of the interstitial tissue caused a twofold increase in the protein kinase activity in the total tissue homogenate and subcellular fractions (12000g X 5 min pellet and 105000g X 60 min supernatant and pellet). 2. A decrease of approx. 40% in the total amount of protein kinase recovered in the soluble fraction (105000g supernatant) occurred in tissue incubated with LH and 3-isobutyl-1-methylxanthine when compared with the controls. No change in total activity was found in the other fractions. 3. LH and 3-isobutyl-1-methylxanthine caused an increase in cyclic AMP concentration in the soluble fraction (from 30 +/- 6 to 450 +/- 40 pmol/mg of protein, means +/- S.E.M., n = 4), but there was little or no increase in the particulate fractions [from 9 +/- 1 to 13 +/- 3 pmol/mg of protein (n = 3) and from 6 +/- 2 to 23 +/- 11 pmol/mg of protein (n = 3) in the 12000g and 105000g pellets respectively]. 4 Addition of 3-isobutyl-1-methylxanthine alone had little effect on protein kinase activity or cyclic AMP concentrations. 5. Little or no protein kinase activity could be demonstrated in subcellular particulate fractions unless Triton X-100 was added; the effect of this detergent was shown to be at least partly due to the inhibition of adenosine triphosphatase activity. 6. In the presence of Triton X-100 approx. 57% of the total protein kinase activity in the homogenate was found in the 105000g supernatant compared with 11% in the 105000g pellet and 32% in the 12000g pellet. 7. In contrast with adipose-tissue protein kinase [Corbin et al. (1973) J. Biol. Chem. 248, 1813-1821] the relative amounts of cyclic AMP-dependent and -dependent enzyme were not affected by dilution of the interstitial-tissue fractions. NaCl (0.5 M) decreased the estimated total amount of protein kinase activity.", "contents": "Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors. Protein kinase activity was determined in subcellular fractions of rat testis interstitial tissue after incubation of the intact tissue with LH (luteinizing hormone) in vitro. Various factors that might have changed the activity of this enzyme during preparation of the fractions before assay were also investigated. The following results were obtained. 1. LH and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor) added together during incubation of the interstitial tissue caused a twofold increase in the protein kinase activity in the total tissue homogenate and subcellular fractions (12000g X 5 min pellet and 105000g X 60 min supernatant and pellet). 2. A decrease of approx. 40% in the total amount of protein kinase recovered in the soluble fraction (105000g supernatant) occurred in tissue incubated with LH and 3-isobutyl-1-methylxanthine when compared with the controls. No change in total activity was found in the other fractions. 3. LH and 3-isobutyl-1-methylxanthine caused an increase in cyclic AMP concentration in the soluble fraction (from 30 +/- 6 to 450 +/- 40 pmol/mg of protein, means +/- S.E.M., n = 4), but there was little or no increase in the particulate fractions [from 9 +/- 1 to 13 +/- 3 pmol/mg of protein (n = 3) and from 6 +/- 2 to 23 +/- 11 pmol/mg of protein (n = 3) in the 12000g and 105000g pellets respectively]. 4 Addition of 3-isobutyl-1-methylxanthine alone had little effect on protein kinase activity or cyclic AMP concentrations. 5. Little or no protein kinase activity could be demonstrated in subcellular particulate fractions unless Triton X-100 was added; the effect of this detergent was shown to be at least partly due to the inhibition of adenosine triphosphatase activity. 6. In the presence of Triton X-100 approx. 57% of the total protein kinase activity in the homogenate was found in the 105000g supernatant compared with 11% in the 105000g pellet and 32% in the 12000g pellet. 7. In contrast with adipose-tissue protein kinase [Corbin et al. (1973) J. Biol. Chem. 248, 1813-1821] the relative amounts of cyclic AMP-dependent and -dependent enzyme were not affected by dilution of the interstitial-tissue fractions. NaCl (0.5 M) decreased the estimated total amount of protein kinase activity."} {"id": "PMID:180977", "title": "Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle.", "content": "Poly(ADP-ribose) polymerase activity in nuclei isolated from differentiating cardiac muscle of the rat has been characterized and its activity measured during development. Optimum enzyme activity is observed at pH 8.5. Poly(ADP-ribose) polymerase is inhibited by ATP, thymidine, nicotinamide, theophylline, 3-isobutyl-1-methylxanthine and caffeine and stimulated by actinomycin D. The activity measured under optimal assay conditions increases during differentiation of cardiac muscle and is inversely related to the rate of DNA synthesis and to the activities of DNA polymerase alpha and thymidine kinase. When DNA synthesis and the activity of DNA polymerase alpha are inhibited in cardiac muscle of the 1-day-old neonatal rat by dibutyryl cyclic AMP or isoproterenol, the specific activity of poly(ADP-ribose) polymerase measured in isolated nuclei is increased. The concentration of NAD+ in cardiac muscle increases during postnatal development. In the adult compared with the 1-day-old neonatal rat the concentration of NAD+ relative to fresh tissue weight, DNA or protein increased 1.7-fold, 5.2-fold or 1.4-fold respectively. The concentration of NAD+ in cardiac muscle of the 1-day-old neonatal rat can be increased by approx. 20% by dibutyryl cyclic AMP. These data suggest that NAD+ and poly(ADP-ribose) polymerase may be involved with the repression of DNA synthesis and cell proliferation in differentiating cardiac muscle.", "contents": "Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle. Poly(ADP-ribose) polymerase activity in nuclei isolated from differentiating cardiac muscle of the rat has been characterized and its activity measured during development. Optimum enzyme activity is observed at pH 8.5. Poly(ADP-ribose) polymerase is inhibited by ATP, thymidine, nicotinamide, theophylline, 3-isobutyl-1-methylxanthine and caffeine and stimulated by actinomycin D. The activity measured under optimal assay conditions increases during differentiation of cardiac muscle and is inversely related to the rate of DNA synthesis and to the activities of DNA polymerase alpha and thymidine kinase. When DNA synthesis and the activity of DNA polymerase alpha are inhibited in cardiac muscle of the 1-day-old neonatal rat by dibutyryl cyclic AMP or isoproterenol, the specific activity of poly(ADP-ribose) polymerase measured in isolated nuclei is increased. The concentration of NAD+ in cardiac muscle increases during postnatal development. In the adult compared with the 1-day-old neonatal rat the concentration of NAD+ relative to fresh tissue weight, DNA or protein increased 1.7-fold, 5.2-fold or 1.4-fold respectively. The concentration of NAD+ in cardiac muscle of the 1-day-old neonatal rat can be increased by approx. 20% by dibutyryl cyclic AMP. These data suggest that NAD+ and poly(ADP-ribose) polymerase may be involved with the repression of DNA synthesis and cell proliferation in differentiating cardiac muscle."} {"id": "PMID:180978", "title": "Nitrogenase of Azotobacter chroococcum. Kinetics of the reduction of oxidized iron-protein by sodium dithionite.", "content": "The kinetics of the reduction of oxidized Fe-protein of nitrogenase from Azotobacter chroococcum by sodium dithionite were studied by stopped-flow and rapid-freezing e.p.r. (electron-paramagnetic-resonance) spectroscopy. The appearance of the gav. = 1.94 e.p.r. signal (0.24 electron integrated intensity/mol) was associated with a one-electron reduction by SO2--with k greater than 10(8)M-1-S-1 at 23 degrees C. A value of k = 1.75s-1 was obtained for the rate of dissociation of S2O42- into 2SO2-- at 23 degrees C. Further reductions by SO2-- occurred in three slower phases with rate constants in the range 10(4) -10(6)M-1-S-1. These latter phases have no corresponding e.p.r. signal changes and are probably associated with enzymically inactive protein. The high rate of reduction by SO2-- of the Fe-protein alone (k greater than 10(8)M-1-S-1) relative to the rate of oxidation of the Fe-protein in the catalytically active Fe:Mo-Fe protein complex (k = 2.2 X 1O(2)s-1) and the observation that in the steady state the Fe-protein is substantially oxidized means that at normal assay concentrations another reaction must limit the rate of reduction of Fe-protein during turnover.", "contents": "Nitrogenase of Azotobacter chroococcum. Kinetics of the reduction of oxidized iron-protein by sodium dithionite. The kinetics of the reduction of oxidized Fe-protein of nitrogenase from Azotobacter chroococcum by sodium dithionite were studied by stopped-flow and rapid-freezing e.p.r. (electron-paramagnetic-resonance) spectroscopy. The appearance of the gav. = 1.94 e.p.r. signal (0.24 electron integrated intensity/mol) was associated with a one-electron reduction by SO2--with k greater than 10(8)M-1-S-1 at 23 degrees C. A value of k = 1.75s-1 was obtained for the rate of dissociation of S2O42- into 2SO2-- at 23 degrees C. Further reductions by SO2-- occurred in three slower phases with rate constants in the range 10(4) -10(6)M-1-S-1. These latter phases have no corresponding e.p.r. signal changes and are probably associated with enzymically inactive protein. The high rate of reduction by SO2-- of the Fe-protein alone (k greater than 10(8)M-1-S-1) relative to the rate of oxidation of the Fe-protein in the catalytically active Fe:Mo-Fe protein complex (k = 2.2 X 1O(2)s-1) and the observation that in the steady state the Fe-protein is substantially oxidized means that at normal assay concentrations another reaction must limit the rate of reduction of Fe-protein during turnover."} {"id": "PMID:180979", "title": "State and accessibility of zinic in yeast alcohol dehydrogenase.", "content": "1. Yeast alcohol dehydrogenase (EC 1.1.1.1) is inhibited in the presence of 1,10-phenanthroline. 2. A conformational change in the enzyme's structure is induced by 1,10-phenanthroline, and is abolished in the presence of NADH. 1,10-Phenanthroline binds to the enzyme competitively with respect to NADH, with a stoicheiometry of 2 mol of 1,10-phenanthroline/144000g of enzyme. 3. 1,10-Phenanthroline induces a time-dependent dissociation of Zn2+ from the enzyme, which is in correlation with its inhibitions. 4. Spectrophotometric measurement indicates that the dissociation of half (2 zinc atoms/tetramer) of the total zinc content of the enzyme correlates with the full inhibition of its activity. Measurement of the tightly bound Zn2+ by atomic absorption photometry confirms this. 5. A proposition is advanced that the tetrameric molecule of yeast alcohol dehydrogenase possesses an inherent asymmetry, with four monomeric subunits being arranged in two mutually symmetrical pairs.", "contents": "State and accessibility of zinic in yeast alcohol dehydrogenase. 1. Yeast alcohol dehydrogenase (EC 1.1.1.1) is inhibited in the presence of 1,10-phenanthroline. 2. A conformational change in the enzyme's structure is induced by 1,10-phenanthroline, and is abolished in the presence of NADH. 1,10-Phenanthroline binds to the enzyme competitively with respect to NADH, with a stoicheiometry of 2 mol of 1,10-phenanthroline/144000g of enzyme. 3. 1,10-Phenanthroline induces a time-dependent dissociation of Zn2+ from the enzyme, which is in correlation with its inhibitions. 4. Spectrophotometric measurement indicates that the dissociation of half (2 zinc atoms/tetramer) of the total zinc content of the enzyme correlates with the full inhibition of its activity. Measurement of the tightly bound Zn2+ by atomic absorption photometry confirms this. 5. A proposition is advanced that the tetrameric molecule of yeast alcohol dehydrogenase possesses an inherent asymmetry, with four monomeric subunits being arranged in two mutually symmetrical pairs."} {"id": "PMID:180980", "title": "The binding of calcium to a salivary phosphoprotein, protein A, common to human parotid and submandibular secretions.", "content": "The binding of Ca2+ to a previously described phosphoprotein from human parotid saliva, protein A [Bennick (1975) Biochem J. 145, 557-567] was studied by means of equilibrium dialysis. In 5 mM-Tris/HC1 buffer, pH7.5, protein A bound 664nmol of Ca/mg of protein. Km was determined to be 181 muM and the binding of Ca2+ to the protein was non-co-operative. The binding of Ca2+ apparently occurs to side-chain carboxyl groups in the protein, but protein phosphate is of minor if any importance in calcium binding. Hydrolysis of protein A by trypsin and collagenase or heating of the protein at 60 degrees or 100 degrees C did not affect Ca2+ binding. The Ca2+ binding decreases with increased concentration of the dialysis buffer and on the addition of SrCl2, or MgCl2 or MnCl2 to the dialysis buffer. Protein A does not aggregate in the presence of Ca2+, since the s20,w was identical when determined in the presence (1.30S) and absence (1.35S) of CaCl2. By use of a specific antiserum to protein A it was found that protein C [Bennick & Connell (1971) Biochem. J. 123, 455-464] and perhaps minor related components cross-reacted with protein A. No other salivary proteins showed immunological similarity. Proteins A and C were also present in submandibular saliva. The possible functions of protein A are discussed.", "contents": "The binding of calcium to a salivary phosphoprotein, protein A, common to human parotid and submandibular secretions. The binding of Ca2+ to a previously described phosphoprotein from human parotid saliva, protein A [Bennick (1975) Biochem J. 145, 557-567] was studied by means of equilibrium dialysis. In 5 mM-Tris/HC1 buffer, pH7.5, protein A bound 664nmol of Ca/mg of protein. Km was determined to be 181 muM and the binding of Ca2+ to the protein was non-co-operative. The binding of Ca2+ apparently occurs to side-chain carboxyl groups in the protein, but protein phosphate is of minor if any importance in calcium binding. Hydrolysis of protein A by trypsin and collagenase or heating of the protein at 60 degrees or 100 degrees C did not affect Ca2+ binding. The Ca2+ binding decreases with increased concentration of the dialysis buffer and on the addition of SrCl2, or MgCl2 or MnCl2 to the dialysis buffer. Protein A does not aggregate in the presence of Ca2+, since the s20,w was identical when determined in the presence (1.30S) and absence (1.35S) of CaCl2. By use of a specific antiserum to protein A it was found that protein C [Bennick & Connell (1971) Biochem. J. 123, 455-464] and perhaps minor related components cross-reacted with protein A. No other salivary proteins showed immunological similarity. Proteins A and C were also present in submandibular saliva. The possible functions of protein A are discussed."} {"id": "PMID:180981", "title": "Formation of angiotensin III by angiotensin-converting enzyme.", "content": "Angiotensin III is formed from des-Asp1 -angiotensin I by angiotensin-converting enzyme. The Km (11 muM) of the reaction is one-third of that for the conversion of angiotensin I into angiotensin II. As suggested by the Km values, bradykinin, peptide BPP9a and angiotensins II and III are better inhibitors of the formation of angiotensin II than of the formation of angiotensin III.", "contents": "Formation of angiotensin III by angiotensin-converting enzyme. Angiotensin III is formed from des-Asp1 -angiotensin I by angiotensin-converting enzyme. The Km (11 muM) of the reaction is one-third of that for the conversion of angiotensin I into angiotensin II. As suggested by the Km values, bradykinin, peptide BPP9a and angiotensins II and III are better inhibitors of the formation of angiotensin II than of the formation of angiotensin III."} {"id": "PMID:180982", "title": "Electron-paramagnetic-resonance studies on the molybdenum of nitrate reductase from Escherichia coli K12.", "content": "Studies on the respiratory nitrate reductase (EC 1.7.99.4) from Escherichia coli K12 by electron-paramagnetic-resonance spectroscopy indicate that its molybdenum centre is comparable with that in other molybdenum-containing enzymes. Two Mo(V) signals may be observed; one shows interaction of Mo(V) with a proton exchangeable with the solvent and has: A (1H) 0.9-1.2mT; g1 = 1.999; g2=1.985; g3 = 1.964; gav. = 1.983. Molybdenum of both signal-giving species may be reduced with dithionite and reoxidized with nitrate.", "contents": "Electron-paramagnetic-resonance studies on the molybdenum of nitrate reductase from Escherichia coli K12. Studies on the respiratory nitrate reductase (EC 1.7.99.4) from Escherichia coli K12 by electron-paramagnetic-resonance spectroscopy indicate that its molybdenum centre is comparable with that in other molybdenum-containing enzymes. Two Mo(V) signals may be observed; one shows interaction of Mo(V) with a proton exchangeable with the solvent and has: A (1H) 0.9-1.2mT; g1 = 1.999; g2=1.985; g3 = 1.964; gav. = 1.983. Molybdenum of both signal-giving species may be reduced with dithionite and reoxidized with nitrate."} {"id": "PMID:180983", "title": "A new non-functional form of milk xanthine oxidase containing stable quinquivalent molybdenum.", "content": "A new non-functional modified form of milk xanthine oxidase is described. This contains molybdenum in a quinquivalent state, which is resistant to both oxidation and reduction. The new species is derived from the native enzyme in a two-step process. The first step is the conversion into the desulpho form, via loss of the 'persulphide' sulphur, and the second involves reaction with ethylene glycol or other reagents. The species gives a characteristic Mo(V) electron-paramagnetic-resonance signal, without proton splittings, designated Resting II. This is virtually identical with signals reported previously from resting turkey liver xanthine dehydrogenase and rabbit liver aldehyde oxidase. The possibility is discussed that species Resting II, prepared with ethylene glycol, contains a -COCH2OH residue bound to a nitrogen ligand of molybdenum.", "contents": "A new non-functional form of milk xanthine oxidase containing stable quinquivalent molybdenum. A new non-functional modified form of milk xanthine oxidase is described. This contains molybdenum in a quinquivalent state, which is resistant to both oxidation and reduction. The new species is derived from the native enzyme in a two-step process. The first step is the conversion into the desulpho form, via loss of the 'persulphide' sulphur, and the second involves reaction with ethylene glycol or other reagents. The species gives a characteristic Mo(V) electron-paramagnetic-resonance signal, without proton splittings, designated Resting II. This is virtually identical with signals reported previously from resting turkey liver xanthine dehydrogenase and rabbit liver aldehyde oxidase. The possibility is discussed that species Resting II, prepared with ethylene glycol, contains a -COCH2OH residue bound to a nitrogen ligand of molybdenum."} {"id": "PMID:180984", "title": "Observations on the different substrate behavior of tropocollagen molecules in solution and intermolecularly cross-linked tropocollagen within insoluble polymeric collagen fibrils.", "content": "Bacterial collagenase was used to compare the extent of digestion of tropocollagen monomers in solution and in reconstituted fibrils with that of tropocollagen molecules intermolecularly cross-linked within insoluble polymeric collagen fibrils obtained from mature tendons at given time-intervals. The extent of digestion of tropocollagen monomers in solution was directly proportional to the enzyme concentration (a range of enzyme substrate molar ratios 1:200 to 1:10 was used). The extent of digestion of polymeric collagen was followed by measuring the solubilization of fluorescent peptides from fluorescent-labelled insoluble polymeric collagen fibrils. The extent of digestion of tropocollagen within polymeric collagen was linear over a very small range of enzyme concentrations, when the enzyme/substrate ratio in the reaction mixture was less than 1:400 on a molecular basis. The behavior of tropocollagen in the form of reconstituted collagen fibrils, which had been matured at 37 degrees C for 8 weeks, was intermediate between the behaviour of solutions of tropocollagen and insoluble polymeric collagen fibrils. The significance of the results is discussed in terms of the structure of polymeric collagen fibrils and the protection against enzymic attack provided by tropocollagen molecules on the circumference of the fibril. The results suggest that assays of collagenase activities based on tropocollagen as substrate cannot be directly related to the ability of these enzymes to degrade mature insoluble collagen fibrils.", "contents": "Observations on the different substrate behavior of tropocollagen molecules in solution and intermolecularly cross-linked tropocollagen within insoluble polymeric collagen fibrils. Bacterial collagenase was used to compare the extent of digestion of tropocollagen monomers in solution and in reconstituted fibrils with that of tropocollagen molecules intermolecularly cross-linked within insoluble polymeric collagen fibrils obtained from mature tendons at given time-intervals. The extent of digestion of tropocollagen monomers in solution was directly proportional to the enzyme concentration (a range of enzyme substrate molar ratios 1:200 to 1:10 was used). The extent of digestion of polymeric collagen was followed by measuring the solubilization of fluorescent peptides from fluorescent-labelled insoluble polymeric collagen fibrils. The extent of digestion of tropocollagen within polymeric collagen was linear over a very small range of enzyme concentrations, when the enzyme/substrate ratio in the reaction mixture was less than 1:400 on a molecular basis. The behavior of tropocollagen in the form of reconstituted collagen fibrils, which had been matured at 37 degrees C for 8 weeks, was intermediate between the behaviour of solutions of tropocollagen and insoluble polymeric collagen fibrils. The significance of the results is discussed in terms of the structure of polymeric collagen fibrils and the protection against enzymic attack provided by tropocollagen molecules on the circumference of the fibril. The results suggest that assays of collagenase activities based on tropocollagen as substrate cannot be directly related to the ability of these enzymes to degrade mature insoluble collagen fibrils."} {"id": "PMID:180985", "title": "Selective inactivation of the transacylase components of the 2-oxo acid dehydrogenase multienzyme complexes of Escherichia coli.", "content": "1. The reaction of the pyruvate dehydrogenase multienzyme complex of Escherichia coli with maleimides was examined. In the absence of substrates, the complex showed little or no reaction with N-ethylmaleimide. However, in the presence of pyruvate and N-ethylmaleimide, inhibition of the pyruvate dehydrogenase complex was rapid. Modification of the enzyme was restricted to the transacetylase component and the inactivation was proportional to the extent of modification. The lipoamide dehydrogenase activity of the complex was unaffected by the treatment. The simplest explanation is that the lipoyl groups on the transacetylase are reductively acetylated by following the initial stages of the normal catalytic cycle, but are thereby made susceptible to modification. Attempts to characterize the reaction product strongly support this conclusion. 2. Similarly, in the presence of N-ethylmaleimide and NADH, much of the pyruvate dehydrogenase activity was lost within seconds, whereas the lipoamide dehydrogenase activity of the complex disappeared more slowly: the initial site of the reaction with the complex was found to be in the lipoyl transacetylase component. The simplest interpretation of these experiments is that NADH reduces the covalently bound lipoyl groups on the transacetylase by means of the associated lipoamide dehydrogenase component, thereby rendering them susceptible to modification. However, the dependence of the rate and extent of inactivation on NADH concentration was complex and it proved impossible to inhibit the pyruvate dehydrogenase activity completely without unacceptable modification of the other component enzymes. 3. The catalytic reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) by NADH in the presence of the pyruvate dehydrogenase complex was demonstrated. A new mechanism for this reaction is proposed in which NADH causes reduction of the enzyme-bound lipoic acid by means of the associated lipoamide dehydrogenase component and the dihydrolipoamide is then oxidized back to the disulphide form by reaction with 5,5'-dithiobis-(2-nitrobenzoic acid). 4. A maleimide with a relatively bulky N-substituent, N-(4-diemthylamino-3,5-dinitrophenyl)maleimide, was an effective replacement for N-ethylmaleimide in these reactions with the pyruvate dehydrogenase complex. 5. The 2-oxoglutarate dehydrogenase complex of E. coli behaved very similarly to the pyruvate dehydrogenase complex, in accord with the generally accepted mechanisms of the two enzymes. 6. The treatment of the 2-oxo acid dehydrogenase complexes with maleimides in the presence of the appropriate 2-oxo acid substrate provides a simple method for selectively inhibiting the transacylase components and for introducing reporter groups on to the lipoyl groups covalently bound to those components.", "contents": "Selective inactivation of the transacylase components of the 2-oxo acid dehydrogenase multienzyme complexes of Escherichia coli. 1. The reaction of the pyruvate dehydrogenase multienzyme complex of Escherichia coli with maleimides was examined. In the absence of substrates, the complex showed little or no reaction with N-ethylmaleimide. However, in the presence of pyruvate and N-ethylmaleimide, inhibition of the pyruvate dehydrogenase complex was rapid. Modification of the enzyme was restricted to the transacetylase component and the inactivation was proportional to the extent of modification. The lipoamide dehydrogenase activity of the complex was unaffected by the treatment. The simplest explanation is that the lipoyl groups on the transacetylase are reductively acetylated by following the initial stages of the normal catalytic cycle, but are thereby made susceptible to modification. Attempts to characterize the reaction product strongly support this conclusion. 2. Similarly, in the presence of N-ethylmaleimide and NADH, much of the pyruvate dehydrogenase activity was lost within seconds, whereas the lipoamide dehydrogenase activity of the complex disappeared more slowly: the initial site of the reaction with the complex was found to be in the lipoyl transacetylase component. The simplest interpretation of these experiments is that NADH reduces the covalently bound lipoyl groups on the transacetylase by means of the associated lipoamide dehydrogenase component, thereby rendering them susceptible to modification. However, the dependence of the rate and extent of inactivation on NADH concentration was complex and it proved impossible to inhibit the pyruvate dehydrogenase activity completely without unacceptable modification of the other component enzymes. 3. The catalytic reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) by NADH in the presence of the pyruvate dehydrogenase complex was demonstrated. A new mechanism for this reaction is proposed in which NADH causes reduction of the enzyme-bound lipoic acid by means of the associated lipoamide dehydrogenase component and the dihydrolipoamide is then oxidized back to the disulphide form by reaction with 5,5'-dithiobis-(2-nitrobenzoic acid). 4. A maleimide with a relatively bulky N-substituent, N-(4-diemthylamino-3,5-dinitrophenyl)maleimide, was an effective replacement for N-ethylmaleimide in these reactions with the pyruvate dehydrogenase complex. 5. The 2-oxoglutarate dehydrogenase complex of E. coli behaved very similarly to the pyruvate dehydrogenase complex, in accord with the generally accepted mechanisms of the two enzymes. 6. The treatment of the 2-oxo acid dehydrogenase complexes with maleimides in the presence of the appropriate 2-oxo acid substrate provides a simple method for selectively inhibiting the transacylase components and for introducing reporter groups on to the lipoyl groups covalently bound to those components."} {"id": "PMID:180986", "title": "Kinetic studies on the binding of cyanide to oxygenated cytochrome c oxidase.", "content": "The reaction of cyanide with oxygenated cytochrome c oxidase was followed by means of flow-flash techniques. The oxygenated form, produced after photolysis of the partially reduced CO complex in the presence of cyanide and O2, shows cyanide-binding properties distinct from those of both the oxidized and the reduced forms of the protein. The binding is a single process (k = 22M-1-S-1) linearly dependent on cyanide concentration to as high as 75 mM. It is suggested that the oxygenated form is a conformational variant of the oxidized protein.", "contents": "Kinetic studies on the binding of cyanide to oxygenated cytochrome c oxidase. The reaction of cyanide with oxygenated cytochrome c oxidase was followed by means of flow-flash techniques. The oxygenated form, produced after photolysis of the partially reduced CO complex in the presence of cyanide and O2, shows cyanide-binding properties distinct from those of both the oxidized and the reduced forms of the protein. The binding is a single process (k = 22M-1-S-1) linearly dependent on cyanide concentration to as high as 75 mM. It is suggested that the oxygenated form is a conformational variant of the oxidized protein."} {"id": "PMID:181009", "title": "Fine structural analysis of rabbit synovial cells. II. Fine structure and rosette-forming cells of explant and monolayer cultures.", "content": "The fine structure and plasma membrane receptors of explant and monolayer cells of normal rabbit synovium were studied. In explants about 10% of the cells were round and formed rosettes with IgC and C3 markers, whereas the remaining cells were stellate, resembled young fibroblasts, and had no receptors for IgG and complement. Monolayer cells looked like fibroblasts, produced fine extracellular fibrils and hyaluronate, and formed no rosettes. Thus early cultures contain both macrophages and fibroblasts but only the latter persist in monolayer.", "contents": "Fine structural analysis of rabbit synovial cells. II. Fine structure and rosette-forming cells of explant and monolayer cultures. The fine structure and plasma membrane receptors of explant and monolayer cells of normal rabbit synovium were studied. In explants about 10% of the cells were round and formed rosettes with IgC and C3 markers, whereas the remaining cells were stellate, resembled young fibroblasts, and had no receptors for IgG and complement. Monolayer cells looked like fibroblasts, produced fine extracellular fibrils and hyaluronate, and formed no rosettes. Thus early cultures contain both macrophages and fibroblasts but only the latter persist in monolayer."} {"id": "PMID:181013", "title": "Roentgenographic aspects of calcium pyrophosphate dihydrate crystal deposition disease (pseudogout).", "content": "A comprehensive review of the roentgenographic features of calcium pyrophosphate crystal deposition disease (pseudogout) is presented. The roentgenographic techniques are reviewed. Those recommended as optimal are as follows: for small peripheral joints, industrial Type M film with contact exposure; for large central joints, direct radiographic magnification (3-4 X) with a microfocus tube. The classic appearances of articular chondrocalcinosis in fibrocartilage, hyaline cartilage, and capsular structures are discussed. Distinctive features of pyrophosphate arthropathy, including the distribution of involvement and the degree of destruction, are emphasized. Finally, the relationship among articular chondrocalcinosis, arthropathy, microscopic crystals, and symptoms is discussed.", "contents": "Roentgenographic aspects of calcium pyrophosphate dihydrate crystal deposition disease (pseudogout). A comprehensive review of the roentgenographic features of calcium pyrophosphate crystal deposition disease (pseudogout) is presented. The roentgenographic techniques are reviewed. Those recommended as optimal are as follows: for small peripheral joints, industrial Type M film with contact exposure; for large central joints, direct radiographic magnification (3-4 X) with a microfocus tube. The classic appearances of articular chondrocalcinosis in fibrocartilage, hyaline cartilage, and capsular structures are discussed. Distinctive features of pyrophosphate arthropathy, including the distribution of involvement and the degree of destruction, are emphasized. Finally, the relationship among articular chondrocalcinosis, arthropathy, microscopic crystals, and symptoms is discussed."} {"id": "PMID:181027", "title": "Determination of disulfiram and its metabolites in human blood.", "content": "This work was initiated by the lack of a sensitive method for the determination of disulfiram and its metabolites in blood of patients treated with this drug. A method is described which allows the separate determination of carbon disulfide, free diethyldithiocarbamate and disulfides derived from disulfiram with adequate precision in 10 ml patient blood. It is based on a spectrophotometric determination of a yellow compound formed by trapping carbon disulfide produced from diethyldithiocarbamate and disulfiram in an ethanolic solution of diethylamine and copper(II)-acetate. Good quantitation of disulfiram and diethyldithiocarbamate in blood was achieved by trapping carbon disulfide produced when formic acid and cystein were added to the samples. During daily administration of 200 mg disulfiram to humans, concentrations of zero to 0.6 mug carbon disulfide and 0.2 to 1.0 mug diethyldithiocarbamate per ml blood were found using this method.", "contents": "Determination of disulfiram and its metabolites in human blood. This work was initiated by the lack of a sensitive method for the determination of disulfiram and its metabolites in blood of patients treated with this drug. A method is described which allows the separate determination of carbon disulfide, free diethyldithiocarbamate and disulfides derived from disulfiram with adequate precision in 10 ml patient blood. It is based on a spectrophotometric determination of a yellow compound formed by trapping carbon disulfide produced from diethyldithiocarbamate and disulfiram in an ethanolic solution of diethylamine and copper(II)-acetate. Good quantitation of disulfiram and diethyldithiocarbamate in blood was achieved by trapping carbon disulfide produced when formic acid and cystein were added to the samples. During daily administration of 200 mg disulfiram to humans, concentrations of zero to 0.6 mug carbon disulfide and 0.2 to 1.0 mug diethyldithiocarbamate per ml blood were found using this method."} {"id": "PMID:181028", "title": "[The effect of carbocromen on cardiac cyclic adenosine-monophosphate].", "content": "The coronary-active drug 3-2-diethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen, Intensain) is known to be an inhibitor of phosphodiesterase (PDE). After intravenous as well as after intraduodenal application of therapeutic doses carbocromen increases in vivo the cAMP-contents of the hearts of rats (by up to 30%) and dogs (up to 50%). This effect is dose related. Correlations between the pharmacokinetic properties and metabolic actions of carbocromen and its influence on the adenylcyclase system are discussed.", "contents": "[The effect of carbocromen on cardiac cyclic adenosine-monophosphate]. The coronary-active drug 3-2-diethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen, Intensain) is known to be an inhibitor of phosphodiesterase (PDE). After intravenous as well as after intraduodenal application of therapeutic doses carbocromen increases in vivo the cAMP-contents of the hearts of rats (by up to 30%) and dogs (up to 50%). This effect is dose related. Correlations between the pharmacokinetic properties and metabolic actions of carbocromen and its influence on the adenylcyclase system are discussed."} {"id": "PMID:181024", "title": "Pyrophosphate release by osteoarthritis cartilage incubates.", "content": "Incubates of articular cartilage from young but not mature rabbits, as well as growth plate cartilage, elaborated PPi into basel Eagle's medium during a 4-hour period. Control rabbit synovial membrane and ear cartilage elaborated negligible amounts of PPi. The PPi was shown to be nondialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. The present authors believe that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites comprise the origin of the PPi in such osteoarthritic cartilage. They further theorize that this PPi output accounts for a considerable fraction, if not all, of the elevated PPi levels found in synovial fluid of patients with osteoarthritis.", "contents": "Pyrophosphate release by osteoarthritis cartilage incubates. Incubates of articular cartilage from young but not mature rabbits, as well as growth plate cartilage, elaborated PPi into basel Eagle's medium during a 4-hour period. Control rabbit synovial membrane and ear cartilage elaborated negligible amounts of PPi. The PPi was shown to be nondialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. The present authors believe that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites comprise the origin of the PPi in such osteoarthritic cartilage. They further theorize that this PPi output accounts for a considerable fraction, if not all, of the elevated PPi levels found in synovial fluid of patients with osteoarthritis."} {"id": "PMID:181040", "title": "Tumour rejection in rats sensitized to embryonic tissue. I. Rejection of tumour cells implanted s.c. and detection of cytotoxic lymphoid cells.", "content": "Wistar rats were sensitized to rat embryonic tissue by immunization with irradiated (5000 rad) rat embryo cells (2 X 10(6) s.c. + 1 X 10(6) i.p.) derived from embryos aged 14-15 days, or by implantation of irradiated (5000 rad) tissue grafts from these embryos. Three to five immunizations were given at weekly intervals, and the rats were then challenged subcutaneously 7-10 days after the final inoculum with minimal tumour-producing tumour cell doses. Immunization with irradiated rat embryo cells failed to influence the growth and development of tumour cells prepared from hepatoma D23 and D30, sarcoma Mc57, mammary carcinoma AAF57 or cells prepared from spontaneously arising mammary carcinomata Sp4 and Sp15. Using adoptive transfer techniques, lymphoid cells from embryo-sensitized rats, when used in a 3000 : 1 ratio (lymphoid cells : tumour cells), were shown effectively to retard the growth of hepatoma D23 in 3 out of 7 experiments performed. Similar adoptive transfer procedures proved ineffective in preventing the growth of mammary carcinoma AAF57. Using in vitro cytotoxicity tests, lymph node cells and spleen cells from embryo-immunized rats were shown to be cytotoxic for several rat tumour cell targets : hepatoma D23 (7/10 tests), sarcoma Mc7 (8/12 tests), mammary carcinoma AAF57 (2/2 tests) and Sp4 (3/4 tests), and for 14-15-day-old rat embryo cells (5/10 tests). In comparative tests lymphoid cells were relatively non-cytotoxic for 20-day-old rat embryo cells (1/6 tests) or cells prepared from adult rat lung or kidney (1/10 tests). The role of embryonic antigen(s) in tumour rejection is discussed.", "contents": "Tumour rejection in rats sensitized to embryonic tissue. I. Rejection of tumour cells implanted s.c. and detection of cytotoxic lymphoid cells. Wistar rats were sensitized to rat embryonic tissue by immunization with irradiated (5000 rad) rat embryo cells (2 X 10(6) s.c. + 1 X 10(6) i.p.) derived from embryos aged 14-15 days, or by implantation of irradiated (5000 rad) tissue grafts from these embryos. Three to five immunizations were given at weekly intervals, and the rats were then challenged subcutaneously 7-10 days after the final inoculum with minimal tumour-producing tumour cell doses. Immunization with irradiated rat embryo cells failed to influence the growth and development of tumour cells prepared from hepatoma D23 and D30, sarcoma Mc57, mammary carcinoma AAF57 or cells prepared from spontaneously arising mammary carcinomata Sp4 and Sp15. Using adoptive transfer techniques, lymphoid cells from embryo-sensitized rats, when used in a 3000 : 1 ratio (lymphoid cells : tumour cells), were shown effectively to retard the growth of hepatoma D23 in 3 out of 7 experiments performed. Similar adoptive transfer procedures proved ineffective in preventing the growth of mammary carcinoma AAF57. Using in vitro cytotoxicity tests, lymph node cells and spleen cells from embryo-immunized rats were shown to be cytotoxic for several rat tumour cell targets : hepatoma D23 (7/10 tests), sarcoma Mc7 (8/12 tests), mammary carcinoma AAF57 (2/2 tests) and Sp4 (3/4 tests), and for 14-15-day-old rat embryo cells (5/10 tests). In comparative tests lymphoid cells were relatively non-cytotoxic for 20-day-old rat embryo cells (1/6 tests) or cells prepared from adult rat lung or kidney (1/10 tests). The role of embryonic antigen(s) in tumour rejection is discussed."} {"id": "PMID:181041", "title": "Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma.", "content": "Inbred rats were injected s.c. with cells of syngeneic hepatoma D23, D23 cells + BCG as a mixed inoculum, mixed inoculum one side and D23 alone contralaterally, or BCG alone. Their blood mononuclear cells were tested weekly for cytotoxicity against D23 target cells using a microcytotoxicity method and their serum was tested for blocking activity against cytotoxicity by lymph node cells from immunized rats. Tumour growth was suppressed when BCG was in contact with tumour cells but tumours grew unhindered if the BCG was given contralaterally. All rats receiving tumour cells, either alone or mixed with BCG, developed cell-mediated cytotoxicity which remained until termination at 35 days. Rats receiving BCG alone showed slight initial cytotoxicity which disappeared after 7 days. Blocking factors appeared in the serum of rats which developed growing tumours but not in rats whose tumours were suppressed by contact with BCG. Splenectomized rats did not differ markedly from intact rats in the in vitro studies or in vivo. It is concluded that development of cell-mediated immunity and blocking factors depends more upon treatment with tumour cells and the subsequent behaviour of the tumour than upon treatment with BCG per se.", "contents": "Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma. Inbred rats were injected s.c. with cells of syngeneic hepatoma D23, D23 cells + BCG as a mixed inoculum, mixed inoculum one side and D23 alone contralaterally, or BCG alone. Their blood mononuclear cells were tested weekly for cytotoxicity against D23 target cells using a microcytotoxicity method and their serum was tested for blocking activity against cytotoxicity by lymph node cells from immunized rats. Tumour growth was suppressed when BCG was in contact with tumour cells but tumours grew unhindered if the BCG was given contralaterally. All rats receiving tumour cells, either alone or mixed with BCG, developed cell-mediated cytotoxicity which remained until termination at 35 days. Rats receiving BCG alone showed slight initial cytotoxicity which disappeared after 7 days. Blocking factors appeared in the serum of rats which developed growing tumours but not in rats whose tumours were suppressed by contact with BCG. Splenectomized rats did not differ markedly from intact rats in the in vitro studies or in vivo. It is concluded that development of cell-mediated immunity and blocking factors depends more upon treatment with tumour cells and the subsequent behaviour of the tumour than upon treatment with BCG per se."} {"id": "PMID:181042", "title": "Bioassay of 2, 4, 5-trichlorophenoxyacetic acid for carcinogenicity in mice.", "content": "Adult mice of strains C3Hf and XVII/G received 2, 4, 5-T by continuous oral administration (80 ppm in the diet). The 2, 4, 5-T preparation contained less than 0-05 ppm of dioxins. In 2, 4, 5-T -treated C3Hf mice a significant increase in the incidence of neoplastic lesions was found. No significant difference was found in the XVII/G strain between the treated and control mice. Rare forms of tumours, which were not observed in the controls, were present in the 2, 4, 5-t -treated C3Hf mice.", "contents": "Bioassay of 2, 4, 5-trichlorophenoxyacetic acid for carcinogenicity in mice. Adult mice of strains C3Hf and XVII/G received 2, 4, 5-T by continuous oral administration (80 ppm in the diet). The 2, 4, 5-T preparation contained less than 0-05 ppm of dioxins. In 2, 4, 5-T -treated C3Hf mice a significant increase in the incidence of neoplastic lesions was found. No significant difference was found in the XVII/G strain between the treated and control mice. Rare forms of tumours, which were not observed in the controls, were present in the 2, 4, 5-t -treated C3Hf mice."} {"id": "PMID:181043", "title": "Effects of short chain alcohols and hydrocarbon compounds on the adenylate cyclase of the skin.", "content": "The cyclic AMP content of epidermal slices is increased by incubation with ethanol, the effect of which is dose-dependent from I to 5% concentration in the incubation media. n-Propanol and acetone are also effective at a concentration equimolar to 5% ethanol. Experimental results suggest that this effect of ethanol is due to activation of adenylate cyclase, rather than to the inactivation of cyclic AMP-phosphodiesterase.", "contents": "Effects of short chain alcohols and hydrocarbon compounds on the adenylate cyclase of the skin. The cyclic AMP content of epidermal slices is increased by incubation with ethanol, the effect of which is dose-dependent from I to 5% concentration in the incubation media. n-Propanol and acetone are also effective at a concentration equimolar to 5% ethanol. Experimental results suggest that this effect of ethanol is due to activation of adenylate cyclase, rather than to the inactivation of cyclic AMP-phosphodiesterase."} {"id": "PMID:181044", "title": "Comparative effects of fructose and glucose on the lipid and carbohydrate metabolism of perfused rat liver.", "content": "1. Livers from rats fed on a standard diet were perfused with whole blood, and infused continuously with glucose and fructose at equimolar rates. 2. Infusion of fructose increased both the secretion of very-low-density-lipoprotein (VLDL)-triglycerides and the incorporation of free fatty acids (FFA) from the perfusate into VLDL-lipids, but neither of these two processes was affected by infusion of glucose. 3. Infusion of fructose decreased the oxidation and increased the esterification of FFA, but glucose infusion had no effect on these processes. When fructose and glucose were infused together was a further decrease in oxidation. 4. When fructose was infused alone or together with glucose, blood concentrations rapidly became stabilized at those found in the hepatic portal vein in vivo, with similar rates of hepatic uptake to those found in the intact animal. Infusion of glucose alone resulted in continuously increasing perfusate glucose concentrations, and rates of uptake which were only 20% of those for fructose. Blood glucose concentrations were reduced, and lactate concentrations were increased by fructose infusion, and when glucose and fructose were infused together there was a greatly increased rate of glucose uptake. 5. Liver glycogen was not affected by the infusion of fructose or glucose alone; however, their combined addition significantly increased its concentration. 6. Uptake of perfusate FFA was not affected by either fructose or glucose infusions. 7. The results are discussed in terms of the differences in nutrition and metabolism between glucose and fructose, with particular reference to the development of hypertriglyceridaemia.", "contents": "Comparative effects of fructose and glucose on the lipid and carbohydrate metabolism of perfused rat liver. 1. Livers from rats fed on a standard diet were perfused with whole blood, and infused continuously with glucose and fructose at equimolar rates. 2. Infusion of fructose increased both the secretion of very-low-density-lipoprotein (VLDL)-triglycerides and the incorporation of free fatty acids (FFA) from the perfusate into VLDL-lipids, but neither of these two processes was affected by infusion of glucose. 3. Infusion of fructose decreased the oxidation and increased the esterification of FFA, but glucose infusion had no effect on these processes. When fructose and glucose were infused together was a further decrease in oxidation. 4. When fructose was infused alone or together with glucose, blood concentrations rapidly became stabilized at those found in the hepatic portal vein in vivo, with similar rates of hepatic uptake to those found in the intact animal. Infusion of glucose alone resulted in continuously increasing perfusate glucose concentrations, and rates of uptake which were only 20% of those for fructose. Blood glucose concentrations were reduced, and lactate concentrations were increased by fructose infusion, and when glucose and fructose were infused together there was a greatly increased rate of glucose uptake. 5. Liver glycogen was not affected by the infusion of fructose or glucose alone; however, their combined addition significantly increased its concentration. 6. Uptake of perfusate FFA was not affected by either fructose or glucose infusions. 7. The results are discussed in terms of the differences in nutrition and metabolism between glucose and fructose, with particular reference to the development of hypertriglyceridaemia."} {"id": "PMID:181045", "title": "Isotope effects in the binding of NADH to equine liver alcohol dehydrogenase.", "content": "The isotope effect upon the binding constant of NADH to equine liver alcohol dehydrogenase is determined with a method in which the isotopic ratio is measured concurrently in the free and the bond form of the coenzyme, by use of a propellent-pressurized ultrafiltration apparatus for separation of the two. The value for KH/KD for the binding constants was 1.00 +/- 0.02 at pH 10.3 and 25 degrees C.", "contents": "Isotope effects in the binding of NADH to equine liver alcohol dehydrogenase. The isotope effect upon the binding constant of NADH to equine liver alcohol dehydrogenase is determined with a method in which the isotopic ratio is measured concurrently in the free and the bond form of the coenzyme, by use of a propellent-pressurized ultrafiltration apparatus for separation of the two. The value for KH/KD for the binding constants was 1.00 +/- 0.02 at pH 10.3 and 25 degrees C."} {"id": "PMID:181046", "title": "Effect of Triton X-100 on the hydrolysis of sphingomyelin by sphingomyelinase of rat brain.", "content": "Mixed dispersions of the nonionic detergent Triton X-100 and sphingomyelin were used as substrate for sphingomyelinase of rat brain. The dependence of the rate of hydrolysis on the concentration of sphingomyelin was measured in two ways: at a fixed concentration of Triton X-100 or at varying concentrations of this detergent, while maintaining a fixed molar ratio of Triton X-100 to sphingomyelin. In either case, the upsilon vs. S curves deviated from the hyperbolic shape predicted by the Michaelis-Menten kinetic theory. These deviations are discussed and interpreted on the basis of the physicochemical properties of the mixed dispersions of detergent and lipid studied in previous papers.", "contents": "Effect of Triton X-100 on the hydrolysis of sphingomyelin by sphingomyelinase of rat brain. Mixed dispersions of the nonionic detergent Triton X-100 and sphingomyelin were used as substrate for sphingomyelinase of rat brain. The dependence of the rate of hydrolysis on the concentration of sphingomyelin was measured in two ways: at a fixed concentration of Triton X-100 or at varying concentrations of this detergent, while maintaining a fixed molar ratio of Triton X-100 to sphingomyelin. In either case, the upsilon vs. S curves deviated from the hyperbolic shape predicted by the Michaelis-Menten kinetic theory. These deviations are discussed and interpreted on the basis of the physicochemical properties of the mixed dispersions of detergent and lipid studied in previous papers."} {"id": "PMID:181047", "title": "Oxidation-reduction properties of several low potential iron-sulfur proteins and of methylviologen.", "content": "Apparent oxidation-reduction potentials at pH 7.0 and 25 degrees C were determined using the H2-hydrogenase system with ferredoxins from the following sources: Clostridium pasteurianum, -403 mV; C tartarovorum, -424 mV; C. acidi-urici, -434 mV; Peptococcus aerogenes, -427 mV; Chromatium D, -482 mV (pH 8.0); B. polymyxa, Fd I, -377 mV, and Fd II, -422 mV; and spinach, -428 mV. The pH dependence of these values was variable, ranging from -2 to -24 mV/pH unit increase for different ferredoxins. Over the range of buffer concentrations between 0.05 and 0.2 M, the potentials did not vary significantly. The number of electrons transferred during reduction (as determined by integrations of EPR spectra and by dithionite titration) is 2 for the first five proteins, while potentiometric data for all the cases fit a Nernst equation for which n = 1. The E degrees' value for the redox indicator methylviologen at pH 7.4 was found to be -460 mV, according to both the H2-hydrogenase system and cyclic voltammetry, significantly different from the value previously reported at higher pH's. Additionally, the presence of C. pasteuranum ferredoxin appears to shift the E degrees value of methylviologen to even more negative values. An analysis of sources of error inherent with potential determinations with H2 and hydrogenase is presented. The electronic and EPR spectra of P. aerogenes ferredoxin, for which the x-ray structure has been published, are given here. It appears that the determination of potentials of ferredoxin and other low-potential porteins with the H2-hydrogenase system affords certain experimental advantages over alternative methods currently employed with these and similar substances.", "contents": "Oxidation-reduction properties of several low potential iron-sulfur proteins and of methylviologen. Apparent oxidation-reduction potentials at pH 7.0 and 25 degrees C were determined using the H2-hydrogenase system with ferredoxins from the following sources: Clostridium pasteurianum, -403 mV; C tartarovorum, -424 mV; C. acidi-urici, -434 mV; Peptococcus aerogenes, -427 mV; Chromatium D, -482 mV (pH 8.0); B. polymyxa, Fd I, -377 mV, and Fd II, -422 mV; and spinach, -428 mV. The pH dependence of these values was variable, ranging from -2 to -24 mV/pH unit increase for different ferredoxins. Over the range of buffer concentrations between 0.05 and 0.2 M, the potentials did not vary significantly. The number of electrons transferred during reduction (as determined by integrations of EPR spectra and by dithionite titration) is 2 for the first five proteins, while potentiometric data for all the cases fit a Nernst equation for which n = 1. The E degrees' value for the redox indicator methylviologen at pH 7.4 was found to be -460 mV, according to both the H2-hydrogenase system and cyclic voltammetry, significantly different from the value previously reported at higher pH's. Additionally, the presence of C. pasteuranum ferredoxin appears to shift the E degrees value of methylviologen to even more negative values. An analysis of sources of error inherent with potential determinations with H2 and hydrogenase is presented. The electronic and EPR spectra of P. aerogenes ferredoxin, for which the x-ray structure has been published, are given here. It appears that the determination of potentials of ferredoxin and other low-potential porteins with the H2-hydrogenase system affords certain experimental advantages over alternative methods currently employed with these and similar substances."} {"id": "PMID:181048", "title": "Enzymatic binding of aminoacyl transfer ribonucleic acid to ribosomes: the study of binding sites of 2' and 3' isomers of aminoacyl transfer ribonucleic acid.", "content": "The mechanism of enzymatic binding of AAtRNA to the acceptor site Escherichia coli ribosomes has been studied using the following aminoacyl oligonucleotides as models of the 3' terminus of AA-tRNA: C-A-Phe, C-A-(2'-Phe)H, and C-A(2'H)Phe. T-psi-C-Gp was used as a model of loop IV of tRNA. The EF-T dependent binding of Phe-tRNA to ribosomes (in the presence of either GTP or GMPPCP) and the GTPase activity associated with EF-T dependent binding of the Phe-tRNA were inhibited by C-A-Phe,C-A(2'Phe)H, and C-A(2'H)Phe. These aminoacyl oligonucleotides inhibit both the formation of ternary complex EF-Tu-GTP-AA-tRNA and the interaction of this complex with the ribosomal A site. The uncoupled EF-Tu dependent GTPase (in the absence of AA-tRNA) was also inhibited by C-A-Phe, C-A(2'Phe)H, and C-A(2'H)Phe, while nonenzymatic binding of Phe-tRNA to the ribosomal A site was inhibited by C-A-Phe and C-A(2'-Phe)H, but not by C-A(2'H)Phe. The tetranucleotide T-psi-C-Gp inhibited both enzyme binding of Phe-tRNA and EF-T dependent GTP hydrolysis. However, inhibition of the latter reaction occured at a lower concentration of T-psi-C-Gp suggesting a specific role of T-psi-C-Gp loop of AA-tRNA in the GTPase reaction. The role of the 2' and 3' isomers of AA-tRNA during enzymatic binding to ribosomes is discussed and it is suggested that 2' leads to 3' transacylation in AA-tRNA is a step which follows GTP hydrolysis but precedes peptide bond formation.", "contents": "Enzymatic binding of aminoacyl transfer ribonucleic acid to ribosomes: the study of binding sites of 2' and 3' isomers of aminoacyl transfer ribonucleic acid. The mechanism of enzymatic binding of AAtRNA to the acceptor site Escherichia coli ribosomes has been studied using the following aminoacyl oligonucleotides as models of the 3' terminus of AA-tRNA: C-A-Phe, C-A-(2'-Phe)H, and C-A(2'H)Phe. T-psi-C-Gp was used as a model of loop IV of tRNA. The EF-T dependent binding of Phe-tRNA to ribosomes (in the presence of either GTP or GMPPCP) and the GTPase activity associated with EF-T dependent binding of the Phe-tRNA were inhibited by C-A-Phe,C-A(2'Phe)H, and C-A(2'H)Phe. These aminoacyl oligonucleotides inhibit both the formation of ternary complex EF-Tu-GTP-AA-tRNA and the interaction of this complex with the ribosomal A site. The uncoupled EF-Tu dependent GTPase (in the absence of AA-tRNA) was also inhibited by C-A-Phe, C-A(2'Phe)H, and C-A(2'H)Phe, while nonenzymatic binding of Phe-tRNA to the ribosomal A site was inhibited by C-A-Phe and C-A(2'-Phe)H, but not by C-A(2'H)Phe. The tetranucleotide T-psi-C-Gp inhibited both enzyme binding of Phe-tRNA and EF-T dependent GTP hydrolysis. However, inhibition of the latter reaction occured at a lower concentration of T-psi-C-Gp suggesting a specific role of T-psi-C-Gp loop of AA-tRNA in the GTPase reaction. The role of the 2' and 3' isomers of AA-tRNA during enzymatic binding to ribosomes is discussed and it is suggested that 2' leads to 3' transacylation in AA-tRNA is a step which follows GTP hydrolysis but precedes peptide bond formation."} {"id": "PMID:181049", "title": "Studies on nitrotyrosine-82 and aminotyrosine-82 derivatives of adrenodoxin. Effects of chemical modification on the complex formation with adrenodoxin reductase.", "content": "The coordination structure of the iron-sulfur center of the nitrotyrosine and the aminotyrosine derivates of bovine adrenodoxin was investigated by electron paramagnetic resonance spectroscopy. The reduced form of both modified samples exhibited signals identical with those for the native protein at g= 1.94 and g=2.01. From these results together with optical absorption and chemical analyses, it was concluded that the coordination structure of the iron-sulfur chromophore for both the derivatives was identical with the binuclear tetrahedral structure of native adrenodoxin. The configuration of the iron-binding area in nitro- and amino-adrenodoxin was studied by ovserving the circular dichroism spectra between 350 and 600 nm. The maxima for the nitro or amino derivatives were all identical with those for the native protein but different in the magnitude of their molar ellipticity. The molar ellipticities at 440 nm were 45.8 X 10(3), 14.5 X 10(3), and 9.5 X 10(6) deg cm2 per mol of iron for native adrenodoxin, nitro or amino derivative, respectively. These results suggest that the chemical modification of the tyrosine residue causes a conformational change in the iron-binding area. We have previously reported that the enzymatic activities of these reconstituted nitro and amino derivatives toware cytochrome c reduction in the presence of adrenodoxin reductase and reduced nicotinamide adenine dinucleotide phosphate were 19 and 7% of native adrenodoxin, respectively. The cytochrome c reductase activities of nitro- and aminoadrenodixin were drastically affected by the ionic strength of the assay medium, as found in native adrenodoxin. Fluorometric titration of the reductase with aminoadrenodoxin revealed that aminoadrenodoxin forms a 1:1 molar complex with the reductase. These results suggest that both the nitro and amino derivatives form a complex with the reductase. The dissociation constants of nitro- and aminoadrenodoxin for the reductase were 6.1 X 10(-7)M and 3.3 X 10(-7) M at mu = 0.04 and 1.9 X 10(-6) M and 2.0 X 10(-6) M at mu = 0.20, respectively. Comparison of these values with those of native adrenodoxin (approximately 10(-9) M at mu = 0.04 and 2.2 X 10(-7) M at mu = 0.20) suggests that an increase in the dissociation constant for the reductase is responsible for the decreased electron transferring activity of the modified adrenodoxins.", "contents": "Studies on nitrotyrosine-82 and aminotyrosine-82 derivatives of adrenodoxin. Effects of chemical modification on the complex formation with adrenodoxin reductase. The coordination structure of the iron-sulfur center of the nitrotyrosine and the aminotyrosine derivates of bovine adrenodoxin was investigated by electron paramagnetic resonance spectroscopy. The reduced form of both modified samples exhibited signals identical with those for the native protein at g= 1.94 and g=2.01. From these results together with optical absorption and chemical analyses, it was concluded that the coordination structure of the iron-sulfur chromophore for both the derivatives was identical with the binuclear tetrahedral structure of native adrenodoxin. The configuration of the iron-binding area in nitro- and amino-adrenodoxin was studied by ovserving the circular dichroism spectra between 350 and 600 nm. The maxima for the nitro or amino derivatives were all identical with those for the native protein but different in the magnitude of their molar ellipticity. The molar ellipticities at 440 nm were 45.8 X 10(3), 14.5 X 10(3), and 9.5 X 10(6) deg cm2 per mol of iron for native adrenodoxin, nitro or amino derivative, respectively. These results suggest that the chemical modification of the tyrosine residue causes a conformational change in the iron-binding area. We have previously reported that the enzymatic activities of these reconstituted nitro and amino derivatives toware cytochrome c reduction in the presence of adrenodoxin reductase and reduced nicotinamide adenine dinucleotide phosphate were 19 and 7% of native adrenodoxin, respectively. The cytochrome c reductase activities of nitro- and aminoadrenodixin were drastically affected by the ionic strength of the assay medium, as found in native adrenodoxin. Fluorometric titration of the reductase with aminoadrenodoxin revealed that aminoadrenodoxin forms a 1:1 molar complex with the reductase. These results suggest that both the nitro and amino derivatives form a complex with the reductase. The dissociation constants of nitro- and aminoadrenodoxin for the reductase were 6.1 X 10(-7)M and 3.3 X 10(-7) M at mu = 0.04 and 1.9 X 10(-6) M and 2.0 X 10(-6) M at mu = 0.20, respectively. Comparison of these values with those of native adrenodoxin (approximately 10(-9) M at mu = 0.04 and 2.2 X 10(-7) M at mu = 0.20) suggests that an increase in the dissociation constant for the reductase is responsible for the decreased electron transferring activity of the modified adrenodoxins."} {"id": "PMID:181050", "title": "Phosphorylation of the active, A1 component of cholera toxin by protein kinase.", "content": "Cholera toxin, an activator of adenylate cyclase in a wide variety of cells, is a substrate for the phosphotransferase reaction catalyzed by purified cyclic adenosine 5'-monophosphate dependent bovine cardiac muscle protein kinase and the protein associated with human erythrocyte membranes. Phosphorylation occurs when the toxin is dissociated with 5-20 mM dithiothreitol and is restricted to the A1 or \"adenylate cyclase activating\" subunit of the toxin.", "contents": "Phosphorylation of the active, A1 component of cholera toxin by protein kinase. Cholera toxin, an activator of adenylate cyclase in a wide variety of cells, is a substrate for the phosphotransferase reaction catalyzed by purified cyclic adenosine 5'-monophosphate dependent bovine cardiac muscle protein kinase and the protein associated with human erythrocyte membranes. Phosphorylation occurs when the toxin is dissociated with 5-20 mM dithiothreitol and is restricted to the A1 or \"adenylate cyclase activating\" subunit of the toxin."} {"id": "PMID:181051", "title": "Specific, reversible inactivation of phosphofructokinase by fructose-1,6-bisphosphatase. Involvement of adenosine 5'-triphosphate, oleate, and 3-phosphoglycerate.", "content": "Optimal conditions necessary for the reversible inactivation of crystalline rabbit muscle phosphofructokinase by homogeneous rabbit liver fructose-1,6-bisphosphatase have been studied. At higher enzyme levels (to 530 mug/ml of phosphofructokinase) the two proteins were mixed and incubated in a pH 7.5 buffer composed of 50 mM Tris-HC1, 2 mM potassium phosphate, and 0.2 mM dithiothreitol. Aliquots were removed at various times and assayed for enzyme activity. A time dependent inactivation of phosphofructokinase caused by 1-2.3 times its weight of fructose-1,6-bisphosphatase was observed at 30, 23, and 0 degree C. This inactivation did not require the presence of adenosine 5'-triphosphate or Mg2+ in the incubation mixture, but an adenosine 5'-triphosphate concentration of 2.7 mM or greater was required in the assay to keep phosphofructokinase in an inactive form. A mixture of activators (inorganic phosphate, (NH4)2SO4, and adenosine 5'-monophosphate), when added to the assay cuvette, restored nearly all of the expected enzyme activity. Incubations with other proteins, including aldolase, at concentrations equal to or greater than the effective quantity of fructose-1,6-bisphosphatase had no inhibitory effect on phosphofructokinase activity. Removal of tightly bound fructose 1,6-bisphosphate from phosphofructokinase could not explain this inactivation, since several analyses of crystalline phosphofructokinase averaged less than 0.1 mol of fructose 1,6-bisphosphate/320 000 g of enzyme. Furthermore, the inactivation occurred in the absence of Mg2+ where the complete lack of fructose-1-6-bisphosphatase activity was confirmed directly. At lower phosphofructokinase concentrations (0.2-2 mug/ml) the inactivation was studied directly in the assay cuvette. Higher ratios of fructose-1,6-bisphosphatase to phosphofructokinase were necessary in these cases, but oleate and 3-phosphoglycerate acted synergistically with lower amounts of fructose-1,6-bisphosphatase to cause inactivation. The inactivation did not occur when high concentrations of fructose 6-phosphate were present in the assay, or when the level of adenosine 5'-triphosphate was decreased. However, the inactivation was found at pH 8, where the effects of allosteric regulators on phosphofructokinase are greatly reduced. Experiments with rat liver phosphofructokinase showed that this enzyme was also subject to inhibition by rabbit liver fructose 1,6-bisphosphatase under conditions similar to those used in the muscle enzyme studies. Attempts to demonstrate direct interaction between phosphofructokinase and fructose-1,6-bisphosphate by physical methods were unsuccessful. Nevertheless, our results suggest that, under conditions which approximate the physiological state, the presence of fructose-1,6bisphosphatase can cause phosphofructokinase to assume an inactive conformation. This interaction may have a significant role in vivo in controlling the interrelationship between glycolysis and gluconeogenesis.", "contents": "Specific, reversible inactivation of phosphofructokinase by fructose-1,6-bisphosphatase. Involvement of adenosine 5'-triphosphate, oleate, and 3-phosphoglycerate. Optimal conditions necessary for the reversible inactivation of crystalline rabbit muscle phosphofructokinase by homogeneous rabbit liver fructose-1,6-bisphosphatase have been studied. At higher enzyme levels (to 530 mug/ml of phosphofructokinase) the two proteins were mixed and incubated in a pH 7.5 buffer composed of 50 mM Tris-HC1, 2 mM potassium phosphate, and 0.2 mM dithiothreitol. Aliquots were removed at various times and assayed for enzyme activity. A time dependent inactivation of phosphofructokinase caused by 1-2.3 times its weight of fructose-1,6-bisphosphatase was observed at 30, 23, and 0 degree C. This inactivation did not require the presence of adenosine 5'-triphosphate or Mg2+ in the incubation mixture, but an adenosine 5'-triphosphate concentration of 2.7 mM or greater was required in the assay to keep phosphofructokinase in an inactive form. A mixture of activators (inorganic phosphate, (NH4)2SO4, and adenosine 5'-monophosphate), when added to the assay cuvette, restored nearly all of the expected enzyme activity. Incubations with other proteins, including aldolase, at concentrations equal to or greater than the effective quantity of fructose-1,6-bisphosphatase had no inhibitory effect on phosphofructokinase activity. Removal of tightly bound fructose 1,6-bisphosphate from phosphofructokinase could not explain this inactivation, since several analyses of crystalline phosphofructokinase averaged less than 0.1 mol of fructose 1,6-bisphosphate/320 000 g of enzyme. Furthermore, the inactivation occurred in the absence of Mg2+ where the complete lack of fructose-1-6-bisphosphatase activity was confirmed directly. At lower phosphofructokinase concentrations (0.2-2 mug/ml) the inactivation was studied directly in the assay cuvette. Higher ratios of fructose-1,6-bisphosphatase to phosphofructokinase were necessary in these cases, but oleate and 3-phosphoglycerate acted synergistically with lower amounts of fructose-1,6-bisphosphatase to cause inactivation. The inactivation did not occur when high concentrations of fructose 6-phosphate were present in the assay, or when the level of adenosine 5'-triphosphate was decreased. However, the inactivation was found at pH 8, where the effects of allosteric regulators on phosphofructokinase are greatly reduced. Experiments with rat liver phosphofructokinase showed that this enzyme was also subject to inhibition by rabbit liver fructose 1,6-bisphosphatase under conditions similar to those used in the muscle enzyme studies. Attempts to demonstrate direct interaction between phosphofructokinase and fructose-1,6-bisphosphate by physical methods were unsuccessful. Nevertheless, our results suggest that, under conditions which approximate the physiological state, the presence of fructose-1,6bisphosphatase can cause phosphofructokinase to assume an inactive conformation. This interaction may have a significant role in vivo in controlling the interrelationship between glycolysis and gluconeogenesis."} {"id": "PMID:181052", "title": "Cytochrome c induced lateral phase separation in a diphosphatidylglycerol-steroid spin-label model membrane.", "content": "The extrinsic membrane protein cytochrome c binds to lipid mixtures containing negatively charged phospholipids such as diphosphatidylglycerol (DPG). In this study the effect of cytochrome c on the lipid distribution in a DPG-steroid spin-label (3-doxyl-5alpha-cholestane) model membrane system is examined. The electron spin resonance (ESR) line-shape changes indicate that cytochrome c induces lateral phase separation at room temperature. The resulting two-dimensional lipid distribution is nonrandom, consisting of clusters of phospholipids bound to cytochrome c and patches of steroid spin-label molecules. Phase separations are also observed in the three-component system: DPG, phosphatidylcholine, and 3-doxyl-5alpha-cholestane.", "contents": "Cytochrome c induced lateral phase separation in a diphosphatidylglycerol-steroid spin-label model membrane. The extrinsic membrane protein cytochrome c binds to lipid mixtures containing negatively charged phospholipids such as diphosphatidylglycerol (DPG). In this study the effect of cytochrome c on the lipid distribution in a DPG-steroid spin-label (3-doxyl-5alpha-cholestane) model membrane system is examined. The electron spin resonance (ESR) line-shape changes indicate that cytochrome c induces lateral phase separation at room temperature. The resulting two-dimensional lipid distribution is nonrandom, consisting of clusters of phospholipids bound to cytochrome c and patches of steroid spin-label molecules. Phase separations are also observed in the three-component system: DPG, phosphatidylcholine, and 3-doxyl-5alpha-cholestane."} {"id": "PMID:181053", "title": "Characterization of a seventh different subunit of beef heart cytochrome c oxidase. Similarities between the beef heart enzyme and that from other species.", "content": "Beef heart cytochrome c oxidase has been resolved into seven subunits by electrophoresis in highly cross-linked gels containing urea and sodium dodecyl sulfate. The molecular weights of the polypeptides are estimated to be I, 35 400; II, 24 100; III, 21 000; IV, 16 800; V, 12 400; VI, 8200; and VII, 4400. It has been shown that subunits II and III can coelectrophorese on standard sodium dodecyl sulfate-polyacrylamide gels and appear as a single component with an apparent molecular weight of 22 500. This accounts for previous reports that the beef heart enzyme contains only six subunits. Amino acid analysis of the isolated subunits I, II, and III revealed that they have polarities of 35.5, 44.7, and 39.9%, respectively. All three subunits have an extremely high leucine content and a low percentage of basic amino acids relative to subunits IV-VII. The size, number, and properties of subunits in the beef heart cytochrome c oxidase complex suggest that it has essentially the same subunit structure as the complexes isolated from Saccharomyces cerevisiae and Neurospora crassa.", "contents": "Characterization of a seventh different subunit of beef heart cytochrome c oxidase. Similarities between the beef heart enzyme and that from other species. Beef heart cytochrome c oxidase has been resolved into seven subunits by electrophoresis in highly cross-linked gels containing urea and sodium dodecyl sulfate. The molecular weights of the polypeptides are estimated to be I, 35 400; II, 24 100; III, 21 000; IV, 16 800; V, 12 400; VI, 8200; and VII, 4400. It has been shown that subunits II and III can coelectrophorese on standard sodium dodecyl sulfate-polyacrylamide gels and appear as a single component with an apparent molecular weight of 22 500. This accounts for previous reports that the beef heart enzyme contains only six subunits. Amino acid analysis of the isolated subunits I, II, and III revealed that they have polarities of 35.5, 44.7, and 39.9%, respectively. All three subunits have an extremely high leucine content and a low percentage of basic amino acids relative to subunits IV-VII. The size, number, and properties of subunits in the beef heart cytochrome c oxidase complex suggest that it has essentially the same subunit structure as the complexes isolated from Saccharomyces cerevisiae and Neurospora crassa."} {"id": "PMID:181054", "title": "Cytochrome oxidase from Pseudomonas aeruginosa. IV. Reaction with oxygen and carbon monoxide.", "content": "The reaction between a cytochrome oxidase from Pseudomonas aeruginosa and oxygen has been studied by a rapid mixing technique. The data indicate that the heme d1 moiety of the ascorbate-reduced enzyme is oxidized faster than the heme c component. The oxidation of heme d1 is accurately second order with respect to oxygen and has a rate constant of 5.7 - 10(4) M-1 - s-1 at 20 degrees C. The oxidation of the heme c has a first order rate constant of about 8 s-1 at infinite concentration of O2. The results indicate that the rate-limiting step is the internal transfer of electrons from heme c to heme d1. These more rapid reactions are followed by more complicated but smaller abcorbance changes whose origin is still not clear. The reaction of ascorbate-reduced oxidase with CO has also been studied and is second order with a rate constant of 1.8 - 10(4) M-1 - s-1. The initial reaction with CO is followed by a slower reaction of significantly less magnitude. The equilibrium constant for the reaction with CO, calculated as a dissociation constant from titrimetric experiments with dithionite-reduced oxidase, is about 2.3 - 10(-6) M. From these data a rate constant of 0.041 s-1 can be calculated for the dissociation of CO from the enzyme.", "contents": "Cytochrome oxidase from Pseudomonas aeruginosa. IV. Reaction with oxygen and carbon monoxide. The reaction between a cytochrome oxidase from Pseudomonas aeruginosa and oxygen has been studied by a rapid mixing technique. The data indicate that the heme d1 moiety of the ascorbate-reduced enzyme is oxidized faster than the heme c component. The oxidation of heme d1 is accurately second order with respect to oxygen and has a rate constant of 5.7 - 10(4) M-1 - s-1 at 20 degrees C. The oxidation of the heme c has a first order rate constant of about 8 s-1 at infinite concentration of O2. The results indicate that the rate-limiting step is the internal transfer of electrons from heme c to heme d1. These more rapid reactions are followed by more complicated but smaller abcorbance changes whose origin is still not clear. The reaction of ascorbate-reduced oxidase with CO has also been studied and is second order with a rate constant of 1.8 - 10(4) M-1 - s-1. The initial reaction with CO is followed by a slower reaction of significantly less magnitude. The equilibrium constant for the reaction with CO, calculated as a dissociation constant from titrimetric experiments with dithionite-reduced oxidase, is about 2.3 - 10(-6) M. From these data a rate constant of 0.041 s-1 can be calculated for the dissociation of CO from the enzyme."} {"id": "PMID:181055", "title": "Electron spin resonance spectrum of species \"X\" which may function as the primary electron acceptor in photosystem I of green plant photosynthesis.", "content": "Purified Photosystem I particles from spinach when reduced with 10 mM dithionite at pH 9 exhibited a 50% light reversible-ESR Signall (P-700+) at about 10 K. It was possible to show by signal-averaging techniques that a light-reversible ESR spectrum concomitant with the reversible Single 1 can be observed with approximate principal g factors at g = 2.07, g = 1.86 and g = 1.75.", "contents": "Electron spin resonance spectrum of species \"X\" which may function as the primary electron acceptor in photosystem I of green plant photosynthesis. Purified Photosystem I particles from spinach when reduced with 10 mM dithionite at pH 9 exhibited a 50% light reversible-ESR Signall (P-700+) at about 10 K. It was possible to show by signal-averaging techniques that a light-reversible ESR spectrum concomitant with the reversible Single 1 can be observed with approximate principal g factors at g = 2.07, g = 1.86 and g = 1.75."} {"id": "PMID:181056", "title": "Neutral glycosphingolipids of serum lipoproteins in Fabry's disease.", "content": "The neutral glycosphingolipid compositions of lipoprotein fractions of serum from eight healthy male volunteers and three patients with Fabry's disease were determined. Four fractions were studied: very low density lipoprotein (VLDL, d less than 1.006); low density lipoprotein (LDL, d 1.006-1.063); high density lipoprotein (HDL, d 1.063-1.21); and ultracentrifugal residue (Residue, d less than 1.21). All lipoprotein fractions contained the four major neutral glycosphingolipids (glucosylceramide, lactosylceramide, galactosylgalactosylglucosylceramide and N-acetylgalactosaminylgalactosylgalactosylglucosylceramide). The LDL and HDL, however, accounted for most of the total glycosphingolipid (69 and 20%, respectively); only small amounts were demonstrated in the VLDL and Residue. The relative distributions of the glycosphingolipids within the LDL and HDL fractions were similar to the distribution in unfractionated serum. Galactosylgalactosylglucosylceramide levels were 3-5 times normal in all three patients with Fabry's disease, and in two the distribution of the excess lipid among the major lipoprotein fractions was similar to that in the control group. In the third patient, who exhibited the presence of \"sinking pre-beta lipoprotein\", the amount of glycosphingolipid isolated with the HDL was greater than that in the LDL.", "contents": "Neutral glycosphingolipids of serum lipoproteins in Fabry's disease. The neutral glycosphingolipid compositions of lipoprotein fractions of serum from eight healthy male volunteers and three patients with Fabry's disease were determined. Four fractions were studied: very low density lipoprotein (VLDL, d less than 1.006); low density lipoprotein (LDL, d 1.006-1.063); high density lipoprotein (HDL, d 1.063-1.21); and ultracentrifugal residue (Residue, d less than 1.21). All lipoprotein fractions contained the four major neutral glycosphingolipids (glucosylceramide, lactosylceramide, galactosylgalactosylglucosylceramide and N-acetylgalactosaminylgalactosylgalactosylglucosylceramide). The LDL and HDL, however, accounted for most of the total glycosphingolipid (69 and 20%, respectively); only small amounts were demonstrated in the VLDL and Residue. The relative distributions of the glycosphingolipids within the LDL and HDL fractions were similar to the distribution in unfractionated serum. Galactosylgalactosylglucosylceramide levels were 3-5 times normal in all three patients with Fabry's disease, and in two the distribution of the excess lipid among the major lipoprotein fractions was similar to that in the control group. In the third patient, who exhibited the presence of \"sinking pre-beta lipoprotein\", the amount of glycosphingolipid isolated with the HDL was greater than that in the LDL."} {"id": "PMID:181057", "title": "Cholesterol content and sterol synthesis in human skin fibroblasts and rat aortic smooth muscle cells exposed to lipoprotein-depleted serum and high density apolipoprotein/phospholipid mixtures.", "content": "Confluent cultures of human skin fibroblasts and rat aortic smooth muscle cells were shown to lose 15-27% of their cellular cholesterol upon replacement of the fetal calf serum with human high density lipoprotein (50 mug cholesterol/ml) or lipoprotein-depleted serum at a concentration equivalent to 40% whole serum. Addition to the latter medium of high density apoliproprotein/phospholipid mixtures resulted in further enhancement of cellular cholesterol loss which was evident by 12 h of incubation. Human skin fibroblasts that had been enriched in cholesterol by previous incubation with low density lipoprotein lost their cholesterol in the presence of a high density apolipoprotein/sphingomyelin mixture as readily as non-enriched cells. Concomitant with the marked cholesterol depletion there was a stimulation of sterol synthesis from acetate. The more pronounced loss of cellular cholesterol induced by the presence of phosphatidylcholine or sphingomyelin resulted in a greater incorporation of acetate into sterol in both smooth muscle cells and skin fibroblasts. The present findings indicate that peripheral cells, in spite of their capacity to synthesize cholesterol, depend on exogenous cholesterol for the maintenance of normal levels. It is suggested that the native cholesterol \"acceptor\" in the lipoprotein-depleted serum is an apolipoprotein which under the experimental conditions can form a complex with phospholipids and might also represent the physiological cholesterol \"acceptor\" in peripheral lymph.", "contents": "Cholesterol content and sterol synthesis in human skin fibroblasts and rat aortic smooth muscle cells exposed to lipoprotein-depleted serum and high density apolipoprotein/phospholipid mixtures. Confluent cultures of human skin fibroblasts and rat aortic smooth muscle cells were shown to lose 15-27% of their cellular cholesterol upon replacement of the fetal calf serum with human high density lipoprotein (50 mug cholesterol/ml) or lipoprotein-depleted serum at a concentration equivalent to 40% whole serum. Addition to the latter medium of high density apoliproprotein/phospholipid mixtures resulted in further enhancement of cellular cholesterol loss which was evident by 12 h of incubation. Human skin fibroblasts that had been enriched in cholesterol by previous incubation with low density lipoprotein lost their cholesterol in the presence of a high density apolipoprotein/sphingomyelin mixture as readily as non-enriched cells. Concomitant with the marked cholesterol depletion there was a stimulation of sterol synthesis from acetate. The more pronounced loss of cellular cholesterol induced by the presence of phosphatidylcholine or sphingomyelin resulted in a greater incorporation of acetate into sterol in both smooth muscle cells and skin fibroblasts. The present findings indicate that peripheral cells, in spite of their capacity to synthesize cholesterol, depend on exogenous cholesterol for the maintenance of normal levels. It is suggested that the native cholesterol \"acceptor\" in the lipoprotein-depleted serum is an apolipoprotein which under the experimental conditions can form a complex with phospholipids and might also represent the physiological cholesterol \"acceptor\" in peripheral lymph."} {"id": "PMID:181058", "title": "High density lipoproteins reduce the uptake of low density lipoproteins by human endothelial cells in culture.", "content": "Endothelial cells, explanted from human umbilical veins and cultured, maintained morphological characteristics of vascular endothelium. When exposed to human serum lipoproteins, the cells bound and took up low density lipoproteins in preference to high density lipoproteins. High density lipoproteins reduced markedly the uptake of low density lipoproteins and affected surface binding to a lesser extent. These data suggest that the different levels of high density lipoprotein encountered in normal plasma of males and females could modulate differently the transendothelial transport of low density lipoproteins and provide a possible explanation for the lesser severity of atheromatosis in the aortic intima of premenopausal females.", "contents": "High density lipoproteins reduce the uptake of low density lipoproteins by human endothelial cells in culture. Endothelial cells, explanted from human umbilical veins and cultured, maintained morphological characteristics of vascular endothelium. When exposed to human serum lipoproteins, the cells bound and took up low density lipoproteins in preference to high density lipoproteins. High density lipoproteins reduced markedly the uptake of low density lipoproteins and affected surface binding to a lesser extent. These data suggest that the different levels of high density lipoprotein encountered in normal plasma of males and females could modulate differently the transendothelial transport of low density lipoproteins and provide a possible explanation for the lesser severity of atheromatosis in the aortic intima of premenopausal females."} {"id": "PMID:181059", "title": "Phospholipid content, composition and biosynthesis during fetal lung development in the rabbit.", "content": "The phospholipid content and composition of lung wash and lung tissue as well as the activities of the enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol (the major surface active components of pulmonary surfactant) were studied in the rabbit during fetal lung development. In lung wash the amount of phospholipid increased four-fold during the period 27-31 day's gestation. There was a further ten-fold increase following the onset breathing. During the same period the amount of phosphatidylcholine in lung wash increased from 29% of the total phospholipid to 80% while the amount of sphingomyelin decreased from 38% to 2%. The amount of phosphatidylcholine in lung tissue also increased during development but to a much lesser extent. During fetal lung development the activities of choline kinase and cholinephosphate cytidyltransferase changed little, cholinephosphotranserase decreased while lysophosphatidic acid acyltransferase and lysolecithin acyltransferase increased. There was a postnatal increase in the activities of cholinephosphate cytidyltransferase, cholinephosphotransferase and both acyltransferases. The amount of phosphatidylglycerol, as a percentage of the total phospholipid, in lung wash and lung tissue as well as the activity of pulmonary glycerolphosphate phosphatidyltransferase did not change appreciably during development.", "contents": "Phospholipid content, composition and biosynthesis during fetal lung development in the rabbit. The phospholipid content and composition of lung wash and lung tissue as well as the activities of the enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol (the major surface active components of pulmonary surfactant) were studied in the rabbit during fetal lung development. In lung wash the amount of phospholipid increased four-fold during the period 27-31 day's gestation. There was a further ten-fold increase following the onset breathing. During the same period the amount of phosphatidylcholine in lung wash increased from 29% of the total phospholipid to 80% while the amount of sphingomyelin decreased from 38% to 2%. The amount of phosphatidylcholine in lung tissue also increased during development but to a much lesser extent. During fetal lung development the activities of choline kinase and cholinephosphate cytidyltransferase changed little, cholinephosphotranserase decreased while lysophosphatidic acid acyltransferase and lysolecithin acyltransferase increased. There was a postnatal increase in the activities of cholinephosphate cytidyltransferase, cholinephosphotransferase and both acyltransferases. The amount of phosphatidylglycerol, as a percentage of the total phospholipid, in lung wash and lung tissue as well as the activity of pulmonary glycerolphosphate phosphatidyltransferase did not change appreciably during development."} {"id": "PMID:181060", "title": "The effect of two isomeric octadecenoic acids on the lipid metabolism and growth of Novikoff hepatoma cells.", "content": "The origin and metabolism of octadecenoic acid (18 : 1) was examined in intact Novikoff rat hepatoma cells by using labeled precursors and two isomeric octadecenoic acids which differed in their abilities to stimulate cell growth in a serum-free medium. The isomers (ci-6-18 : 1 and cis-9-18 : 1) were measured in the cellular lipid by ozonolysis and reduction of the ozonides. The results indicate that the 18 : 1 fatty acid accumulated in the cell lipid by uptake of the preformed acid from the medium. The cis-9-18 : 1 to 16 : 1 and 20 : 1 fatty acids by chain shortening and chain elongation. Both isomers inhibited de novo fatty acid synthesis from acetate by cells suspended in a serum-free medium. The isomers did not exert coordinate control of both fatty acid and cholesterol biosynthesis in the Novikoff cells.", "contents": "The effect of two isomeric octadecenoic acids on the lipid metabolism and growth of Novikoff hepatoma cells. The origin and metabolism of octadecenoic acid (18 : 1) was examined in intact Novikoff rat hepatoma cells by using labeled precursors and two isomeric octadecenoic acids which differed in their abilities to stimulate cell growth in a serum-free medium. The isomers (ci-6-18 : 1 and cis-9-18 : 1) were measured in the cellular lipid by ozonolysis and reduction of the ozonides. The results indicate that the 18 : 1 fatty acid accumulated in the cell lipid by uptake of the preformed acid from the medium. The cis-9-18 : 1 to 16 : 1 and 20 : 1 fatty acids by chain shortening and chain elongation. Both isomers inhibited de novo fatty acid synthesis from acetate by cells suspended in a serum-free medium. The isomers did not exert coordinate control of both fatty acid and cholesterol biosynthesis in the Novikoff cells."} {"id": "PMID:181061", "title": "Effects of glycerol on VLDL secretion by the isolated rat liver.", "content": "Stimulation of VLDL production by increasing fatty acid availability is now well established. However, a possible regulatory role of glycerol, another lipid precursor, in VLDL synthesis by the liver has not yet been substaniated. The present experiments investigate this problem using the isolated perfused rat liver. [14C] Glycerol uptake and metabolism were studied at two different glycerol concentrations: 1 mumol/perfusate (control) or 1.6 mmol/perfusate. VLDL production and lipid synthesis were investigated using [14C]leucine and several labelled fatty acids as precursors in control and glycerol-overloaded livers. Neoglycogenesis and lipogenesis from glycerol carbons are negligible in our conditions. The absolute amount of glycerol, but not the precentage, taken up by the liver, increased after raising its concentration in the perfusate. A major part of exogenous (plasmatic) glycerol was esterified with endogenous (non plasmatic) fatty acids. Incorporation of radioactive fatty acids into liver or plasma lipids was lower than in the the control group. Significant differences were observed between saturated and unsaturated fatty acids used as lipid precursors. Production of VLDL as assessed by radioactive leucine and fatty acid incorporation in the VLDL of the perfusate was depressed by glycerol. Glycerol partly inhibits the normal stimulation of VLDL production by plasmatic fatty acid overload.", "contents": "Effects of glycerol on VLDL secretion by the isolated rat liver. Stimulation of VLDL production by increasing fatty acid availability is now well established. However, a possible regulatory role of glycerol, another lipid precursor, in VLDL synthesis by the liver has not yet been substaniated. The present experiments investigate this problem using the isolated perfused rat liver. [14C] Glycerol uptake and metabolism were studied at two different glycerol concentrations: 1 mumol/perfusate (control) or 1.6 mmol/perfusate. VLDL production and lipid synthesis were investigated using [14C]leucine and several labelled fatty acids as precursors in control and glycerol-overloaded livers. Neoglycogenesis and lipogenesis from glycerol carbons are negligible in our conditions. The absolute amount of glycerol, but not the precentage, taken up by the liver, increased after raising its concentration in the perfusate. A major part of exogenous (plasmatic) glycerol was esterified with endogenous (non plasmatic) fatty acids. Incorporation of radioactive fatty acids into liver or plasma lipids was lower than in the the control group. Significant differences were observed between saturated and unsaturated fatty acids used as lipid precursors. Production of VLDL as assessed by radioactive leucine and fatty acid incorporation in the VLDL of the perfusate was depressed by glycerol. Glycerol partly inhibits the normal stimulation of VLDL production by plasmatic fatty acid overload."} {"id": "PMID:181062", "title": "Demonstration of a thyrotropin-responsive prostaglandin E2-9-ketoreductase in bovine thyroid.", "content": "1. Prostaglandin E2-9-ketoreductase activity was demonstrated in bovine thyroid homogenates. 2. The enzyme requires reduced pyridine nucleotide and dialysis prior to assay for optimal activity. 3. The products of the reaction, NADP and prostaglandin F2alpha, inhibit enzyme activity. 4. Sigmoidal kinetics are observed when substrate concentration is plotted against enzyme velocity, indicative of an allosteric enzyme. 5. Thyrotropin increases enzyme activity in bovine thyroid slices. This increase is both hormone- and tissue-specific.", "contents": "Demonstration of a thyrotropin-responsive prostaglandin E2-9-ketoreductase in bovine thyroid. 1. Prostaglandin E2-9-ketoreductase activity was demonstrated in bovine thyroid homogenates. 2. The enzyme requires reduced pyridine nucleotide and dialysis prior to assay for optimal activity. 3. The products of the reaction, NADP and prostaglandin F2alpha, inhibit enzyme activity. 4. Sigmoidal kinetics are observed when substrate concentration is plotted against enzyme velocity, indicative of an allosteric enzyme. 5. Thyrotropin increases enzyme activity in bovine thyroid slices. This increase is both hormone- and tissue-specific."} {"id": "PMID:181063", "title": "Effect of adrenergic agonists on phosphatidylinositol labelling in heart and aorta.", "content": "(1) The metabolism of phosphatidylinositol has been investigated in heart fragments and aorta slices incubated with adrenergic agonists. (2) Noradrenaline and isoprenaline had no stimulatory effect on 32Pi incorporation into phosphatidylinositol in cat and guinea-pig hearts. (3) Incorporation of 32Pi into phosphatidylinositol was enhanced by noradrenaline and methoxamine in cat aorta. (4) This information is consistent with the idea that the enhanced phosphatidylinositol turnover produced during adrenergic stimulation is mediated through alpha-adrenergic receptors and not through beta-adrenoceptors.", "contents": "Effect of adrenergic agonists on phosphatidylinositol labelling in heart and aorta. (1) The metabolism of phosphatidylinositol has been investigated in heart fragments and aorta slices incubated with adrenergic agonists. (2) Noradrenaline and isoprenaline had no stimulatory effect on 32Pi incorporation into phosphatidylinositol in cat and guinea-pig hearts. (3) Incorporation of 32Pi into phosphatidylinositol was enhanced by noradrenaline and methoxamine in cat aorta. (4) This information is consistent with the idea that the enhanced phosphatidylinositol turnover produced during adrenergic stimulation is mediated through alpha-adrenergic receptors and not through beta-adrenoceptors."} {"id": "PMID:181064", "title": "Some characteristics of sn-glycero-3-phosphocholine diesterases from rat brain.", "content": "1. sn-Glycero-3-phosphocholine diesterase activities, glycerophosphohydrolase (EC 3.1.4.2) and choline phosphohydrolase (EC 3.1.4.38) from rat brain have been partially purified and characterized using sn-glycere-3-[32P]phosphocholine as substrate and separating the reaction products by anion-exchange chromatography and ionophoresis. 2. Rat brain contained particulate (75%) and soluble (25%) activity from both diesterases. No difference in pH optimum or metal ion requirement for the particulate compared to the soluble enzymes was observed. 3. Glycerophosphohydrolase (EC 3.1.4.2) was purified 60-fold, choline phosphohydrolase (EC E.1.4.38) 120-fold from rat brain supernatant fraction by DEAE-cellulose ion-exchange chromatography and sucrose density gradient centrifugation. The density gradient results in conjunction with dodecyl sulphate-polyacrylamide gel disc electrophoresis yielded molecular weight estimates of 230 000 (monomer 62 000) for choline phosphohydrolase and 120 000 (monomer 70 000) for glycerophosphohydrolase (EC 3.1.4.2). 4. Glycerophosphohydrolase (EC 3.1.4.2) has a pH optimum of 8.9 and a Km for sn-glycero-3-phosphocholine of 0.6 mM. The enzyme is inhibited by EDTA and reactivated by Ca2+. Choline phosphohydrolase (EC 3.1.4.38) has pH optimum 10.5, a Km of 2 mM and is unaffected by EDTA. Both enzymes require Ca2+ for maximum activity.", "contents": "Some characteristics of sn-glycero-3-phosphocholine diesterases from rat brain. 1. sn-Glycero-3-phosphocholine diesterase activities, glycerophosphohydrolase (EC 3.1.4.2) and choline phosphohydrolase (EC 3.1.4.38) from rat brain have been partially purified and characterized using sn-glycere-3-[32P]phosphocholine as substrate and separating the reaction products by anion-exchange chromatography and ionophoresis. 2. Rat brain contained particulate (75%) and soluble (25%) activity from both diesterases. No difference in pH optimum or metal ion requirement for the particulate compared to the soluble enzymes was observed. 3. Glycerophosphohydrolase (EC 3.1.4.2) was purified 60-fold, choline phosphohydrolase (EC E.1.4.38) 120-fold from rat brain supernatant fraction by DEAE-cellulose ion-exchange chromatography and sucrose density gradient centrifugation. The density gradient results in conjunction with dodecyl sulphate-polyacrylamide gel disc electrophoresis yielded molecular weight estimates of 230 000 (monomer 62 000) for choline phosphohydrolase and 120 000 (monomer 70 000) for glycerophosphohydrolase (EC 3.1.4.2). 4. Glycerophosphohydrolase (EC 3.1.4.2) has a pH optimum of 8.9 and a Km for sn-glycero-3-phosphocholine of 0.6 mM. The enzyme is inhibited by EDTA and reactivated by Ca2+. Choline phosphohydrolase (EC 3.1.4.38) has pH optimum 10.5, a Km of 2 mM and is unaffected by EDTA. Both enzymes require Ca2+ for maximum activity."} {"id": "PMID:181065", "title": "Spin lattice relaxation and exchange interaction in a 2-iron, 2-sulphur protein.", "content": "A two-iron-two-sulphur non-haem iron protein, the ferredoxin from Spirulina maxima, has been studied by means of electron paramagnetic resonance (EPR) in the range where the spectrum loses resolution with increasing temperature. The spin-lattice relaxation times were deduced from linewidths measured by spectral simulation and their variation as a function of temperature is interpreted in terms of an Orbach mechanism. On this basis, the exchange integral between the two iron atoms, assuming as antiferromagnetic interaction between them, is estimated to be - 83 cm-1.", "contents": "Spin lattice relaxation and exchange interaction in a 2-iron, 2-sulphur protein. A two-iron-two-sulphur non-haem iron protein, the ferredoxin from Spirulina maxima, has been studied by means of electron paramagnetic resonance (EPR) in the range where the spectrum loses resolution with increasing temperature. The spin-lattice relaxation times were deduced from linewidths measured by spectral simulation and their variation as a function of temperature is interpreted in terms of an Orbach mechanism. On this basis, the exchange integral between the two iron atoms, assuming as antiferromagnetic interaction between them, is estimated to be - 83 cm-1."} {"id": "PMID:181066", "title": "Purification and properties of paramagnetic protein from Clostridium pasteurianum W5.", "content": "The purification to homogeneity of the non-heme iron protein, sometimes referred to as either \"red protein\" or \"paramagnetic protein\", from Clostridium pasteurianum W5 extracts is described and its physicochemical properties studied. This paramagnetic protein (g= 1.94) has a molecular weight of about 25000 and contains two iron and two acid-labile sulfur atoms per mol of protein. Its midpoint potential at pH 7.5, as determined by electron paramagnetic resonance titration, is -300 mV. Optical circular dichroism and electron paramagnetic resonance spectra of the paramagnetic protein are similar to those of two iron-two acid-labile sulfur ferredoxins. The biochemical reduction of the purified protein was also studied.", "contents": "Purification and properties of paramagnetic protein from Clostridium pasteurianum W5. The purification to homogeneity of the non-heme iron protein, sometimes referred to as either \"red protein\" or \"paramagnetic protein\", from Clostridium pasteurianum W5 extracts is described and its physicochemical properties studied. This paramagnetic protein (g= 1.94) has a molecular weight of about 25000 and contains two iron and two acid-labile sulfur atoms per mol of protein. Its midpoint potential at pH 7.5, as determined by electron paramagnetic resonance titration, is -300 mV. Optical circular dichroism and electron paramagnetic resonance spectra of the paramagnetic protein are similar to those of two iron-two acid-labile sulfur ferredoxins. The biochemical reduction of the purified protein was also studied."} {"id": "PMID:181067", "title": "ENDOR from nitrogens and protons in low spin ferric heme and hemoprotein.", "content": "Electron nuclear double resonance (ENDOR) signals have been obtained from iron-linked nitrogens in frozen solutions of cytochrome c, metmyoglobin cyanide, and a low spin protohemin mercaptide complex. Hyperfine couplings from heme protons have also been obtained from metmyoglobin cyanide and from a low spin protohemin cyanide complex. Several of these proton resonances are assigned to specific heme protons.", "contents": "ENDOR from nitrogens and protons in low spin ferric heme and hemoprotein. Electron nuclear double resonance (ENDOR) signals have been obtained from iron-linked nitrogens in frozen solutions of cytochrome c, metmyoglobin cyanide, and a low spin protohemin mercaptide complex. Hyperfine couplings from heme protons have also been obtained from metmyoglobin cyanide and from a low spin protohemin cyanide complex. Several of these proton resonances are assigned to specific heme protons."} {"id": "PMID:181068", "title": "Inactivation of the T7 coliphage by monofunctional alkylating agents. Action of phage adsorption and injection of its DNA.", "content": "Alkylation by ethyl or methyl methanesulfonate to an extent that inactivates more than 99.5% of T7 coliphages has no effect on phage adsorption on Escherichia coli B cells, but decreases the amount of phage DNA injected into the host cells. Depurination interferes with the injection of the phage DNA. Failure to inject the whole phage genome thus appears to be a cause of the immediate as well as of the delayed inactivation of the T7 coliphage treated by monofunctional alkylating agents; the hypothesis that it is the only cause of inactivation, although not very likely, cannot be excluded at the present time.", "contents": "Inactivation of the T7 coliphage by monofunctional alkylating agents. Action of phage adsorption and injection of its DNA. Alkylation by ethyl or methyl methanesulfonate to an extent that inactivates more than 99.5% of T7 coliphages has no effect on phage adsorption on Escherichia coli B cells, but decreases the amount of phage DNA injected into the host cells. Depurination interferes with the injection of the phage DNA. Failure to inject the whole phage genome thus appears to be a cause of the immediate as well as of the delayed inactivation of the T7 coliphage treated by monofunctional alkylating agents; the hypothesis that it is the only cause of inactivation, although not very likely, cannot be excluded at the present time."} {"id": "PMID:181069", "title": "Variation in the molecular size of the DNA from closely related strains of type I herpes simplex virus.", "content": "We have investigated the comparative genome size of five strains of HSV type 1 (HSV-1). Two of these strains have a common origin and differ in their plaque morphology on HeLa cells, one strain is a wild type isolate, and two others are established laboratory strains. All strains show high sequence homology based on the melting behavior of heteroduplexes. The greatest sequence divergence between any two strains was found to be no more than 10%. There are real differences in the size of the genomes of these strains of HSV-1 as measured by electron microscopy. The shortest and largest genomes measured differ in size by 10%, however, the size of the genomes of all strains are within 5% of a median valve of 87-88X106.", "contents": "Variation in the molecular size of the DNA from closely related strains of type I herpes simplex virus. We have investigated the comparative genome size of five strains of HSV type 1 (HSV-1). Two of these strains have a common origin and differ in their plaque morphology on HeLa cells, one strain is a wild type isolate, and two others are established laboratory strains. All strains show high sequence homology based on the melting behavior of heteroduplexes. The greatest sequence divergence between any two strains was found to be no more than 10%. There are real differences in the size of the genomes of these strains of HSV-1 as measured by electron microscopy. The shortest and largest genomes measured differ in size by 10%, however, the size of the genomes of all strains are within 5% of a median valve of 87-88X106."} {"id": "PMID:181070", "title": "Joining of simian virus 40 DNA molecules at endonuclease R Eco Ri sites by polynucleotide ligase and analysis of the products by agarose gel electrophoresis.", "content": "DNA molecules cut with endonuclease R Eco Ri can be joined at Eco Ri cleavage sites by incubation with polynucleotide ligase. In order to define the optimum conditions for this reaction, linear Simian Virus 40 DNA molecules (SV40(Lri)) produced by endonuclease R Eco Ri cleavage of SV40 form i DNA were joined using polynucleotide ligases specified by bacteriophage T4 and Escherichia coli. We have determined that the concentration of the substrate DNA molecules is the most important factor determining the distribution of covalently joined product molecules into a variety of circular and linear monomeric and oligomeric species.", "contents": "Joining of simian virus 40 DNA molecules at endonuclease R Eco Ri sites by polynucleotide ligase and analysis of the products by agarose gel electrophoresis. DNA molecules cut with endonuclease R Eco Ri can be joined at Eco Ri cleavage sites by incubation with polynucleotide ligase. In order to define the optimum conditions for this reaction, linear Simian Virus 40 DNA molecules (SV40(Lri)) produced by endonuclease R Eco Ri cleavage of SV40 form i DNA were joined using polynucleotide ligases specified by bacteriophage T4 and Escherichia coli. We have determined that the concentration of the substrate DNA molecules is the most important factor determining the distribution of covalently joined product molecules into a variety of circular and linear monomeric and oligomeric species."} {"id": "PMID:181071", "title": "The nature of bile salt micelles as studied by deuterium NMR.", "content": "Deuterium NMR of 3alpha,12alpha-dihydroxy-7,7dideutero-5beta-cholanic acid was studied. Molcular sizes obtained from deuterium spin-lattice relaxation time (T1) data of 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid in methanol and in water are in accordance with monometic and tetrameric structures in the two media, respectively. The deuterium T1 and intensity of 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid in aqueous solution at pH 8.0--8.8 were studied as functions of NcC1 and lecithin concentrations. The results indicated that tetramers are in equilibrium with larger aggregates when secondary micelles are formed in the precense of NaC1, and that 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid forms mixed micelles with lecithin with a molecular ratio of 2 : 3.", "contents": "The nature of bile salt micelles as studied by deuterium NMR. Deuterium NMR of 3alpha,12alpha-dihydroxy-7,7dideutero-5beta-cholanic acid was studied. Molcular sizes obtained from deuterium spin-lattice relaxation time (T1) data of 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid in methanol and in water are in accordance with monometic and tetrameric structures in the two media, respectively. The deuterium T1 and intensity of 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid in aqueous solution at pH 8.0--8.8 were studied as functions of NcC1 and lecithin concentrations. The results indicated that tetramers are in equilibrium with larger aggregates when secondary micelles are formed in the precense of NaC1, and that 3alpha,12alpha-dihydroxy-7,7-dideutero-5beta-cholanoic acid forms mixed micelles with lecithin with a molecular ratio of 2 : 3."} {"id": "PMID:181072", "title": "Stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian tissues.", "content": "The crude protein kinase modulator preparations obtained from several rat tissues (aorta, brain heart, liver, lung, skeletal muscle, small intestine and testis) were separated into their stimulatory and inhibitory modulator components by Sephadex G-100 gel filtration. The isolated stimulatory modulator augmented the activity of guanosine 3':5'-monophosphate-dependent protein kinase. The isolated inhibitory modulator, on the other hand, depressed the activity of cyclic AMP-dependent protein kinase; it was without effect on the activity of cyclic GMP-dependent protein kinease. The present findings indicate that in the mammal, apparently in contrast to the arthropoda, separate proteins are responsibile for the stimulatory and the inhibitory activities of protein kinase modulator and that the two classes of cyclic nucleotide-dependent protein kinase are regulated in an opposing manner by these two types of modulators.", "contents": "Stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian tissues. The crude protein kinase modulator preparations obtained from several rat tissues (aorta, brain heart, liver, lung, skeletal muscle, small intestine and testis) were separated into their stimulatory and inhibitory modulator components by Sephadex G-100 gel filtration. The isolated stimulatory modulator augmented the activity of guanosine 3':5'-monophosphate-dependent protein kinase. The isolated inhibitory modulator, on the other hand, depressed the activity of cyclic AMP-dependent protein kinase; it was without effect on the activity of cyclic GMP-dependent protein kinease. The present findings indicate that in the mammal, apparently in contrast to the arthropoda, separate proteins are responsibile for the stimulatory and the inhibitory activities of protein kinase modulator and that the two classes of cyclic nucleotide-dependent protein kinase are regulated in an opposing manner by these two types of modulators."} {"id": "PMID:181073", "title": "Thyroxine-binding proteins in liver and tail of Rana catebeiana undergoing metamorphosis.", "content": "Presence of a thyroxine-binding protein was demonstrated in vivo in cell sap of tail and liver of metamorphosing Rana catesbeiana tadpoles. Thyroxine-binding protein was not present in tail of prematamorphic tadpoles while it appeared during progressing metamorphosis roughly coinciding with the beginning of tail resorption. Susceptibility to pronase indicates that this thyroxine-binding macromolecule is protein in nature. Thyroxine-binding in liver was already present during premetamorphic stages and increased further during metamorphosis. A further difference between tail and liver thyroxine-binding protein was evidenced by molecular sieve chromatography on Sephadex G-200 indicating a molecular weight of thyroxine-binding protein in the tail of 60 000 as opposed to 42 000 for liver. Scatchard analysis of tail cell sap of tadpoles in metamorphic climax revealed a high affinity thyroxing binding site (Kd of 2 - 10(-10) M) of low capacity (1.7 pmol per mg protein) while tadpoles in premetamorphic stage had a thyroxine-binding site of lower affinity (9 - 10(-10) M) and higher capacity (4.8 pmol per mg protein). Thus affinity of thyroxine binding is 4-fold in metamorphic climax and appears to reflect the appearance of thyroxine binding observed in vivo.", "contents": "Thyroxine-binding proteins in liver and tail of Rana catebeiana undergoing metamorphosis. Presence of a thyroxine-binding protein was demonstrated in vivo in cell sap of tail and liver of metamorphosing Rana catesbeiana tadpoles. Thyroxine-binding protein was not present in tail of prematamorphic tadpoles while it appeared during progressing metamorphosis roughly coinciding with the beginning of tail resorption. Susceptibility to pronase indicates that this thyroxine-binding macromolecule is protein in nature. Thyroxine-binding in liver was already present during premetamorphic stages and increased further during metamorphosis. A further difference between tail and liver thyroxine-binding protein was evidenced by molecular sieve chromatography on Sephadex G-200 indicating a molecular weight of thyroxine-binding protein in the tail of 60 000 as opposed to 42 000 for liver. Scatchard analysis of tail cell sap of tadpoles in metamorphic climax revealed a high affinity thyroxing binding site (Kd of 2 - 10(-10) M) of low capacity (1.7 pmol per mg protein) while tadpoles in premetamorphic stage had a thyroxine-binding site of lower affinity (9 - 10(-10) M) and higher capacity (4.8 pmol per mg protein). Thus affinity of thyroxine binding is 4-fold in metamorphic climax and appears to reflect the appearance of thyroxine binding observed in vivo."} {"id": "PMID:181074", "title": "Developmental changes in glycosaminoglycans, collagen and collagenase activity in embryonic chick skin.", "content": "In order to study remodeling of connective tissue during development, changes in glycosaminoglycan, collagen and collagenase activity in embryonic chick skin at various stages have been studied. Collagen content in the skin increased rapidly during days 14 to 18, then leveled off until hatching. Prior to the increase of collagen deposition in the skin, a sharp decrease in chondroitin sulfate was observed between days 11 and 14, while dermatan sulfate increased almost 4 fold during days 12 to 14, then increased steadily until hatching. Hyaluronic acid decreased progressively during the stages investigated (days 11 to 20). At the same stage as the rate of collagen deposition in the tissue became maximal (day 16), the amount of dialyzable hydroxyproline showed a maximum, indicating that an increased rate of collagen deposition in the tissue was accompanied by accelerated collagenolysis. Culture of skin from various stages of embryonic development revealed that 16 day old tissue was potentially capable of secreting the highest levels of collagenase. This collagenase was mostly inactive against soluble collagen and collagen fibrils but could be activated by 3 M NaSCN treatment.", "contents": "Developmental changes in glycosaminoglycans, collagen and collagenase activity in embryonic chick skin. In order to study remodeling of connective tissue during development, changes in glycosaminoglycan, collagen and collagenase activity in embryonic chick skin at various stages have been studied. Collagen content in the skin increased rapidly during days 14 to 18, then leveled off until hatching. Prior to the increase of collagen deposition in the skin, a sharp decrease in chondroitin sulfate was observed between days 11 and 14, while dermatan sulfate increased almost 4 fold during days 12 to 14, then increased steadily until hatching. Hyaluronic acid decreased progressively during the stages investigated (days 11 to 20). At the same stage as the rate of collagen deposition in the tissue became maximal (day 16), the amount of dialyzable hydroxyproline showed a maximum, indicating that an increased rate of collagen deposition in the tissue was accompanied by accelerated collagenolysis. Culture of skin from various stages of embryonic development revealed that 16 day old tissue was potentially capable of secreting the highest levels of collagenase. This collagenase was mostly inactive against soluble collagen and collagen fibrils but could be activated by 3 M NaSCN treatment."} {"id": "PMID:181075", "title": "Aflatoxin inhibition of glucocorticoid finding capacity of rat liver nuclei.", "content": "The effect of aflatoxin B1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [3H]desamethasone-cytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 26 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant. Administration of [3H]dexamethasone to alfatoxin B1 -treated rats produced a similar pattern of glucocorticoid binding distribution in vivo to that observed in vitro. No differences in [3H]dexamethasone-cytoplasmic receptor binding between control and alfatoxin B1 -treated rats were found, whereas nuclear [3H]dexanthasone binding was reduced 34% by alfatoxin B1 -treatment.", "contents": "Aflatoxin inhibition of glucocorticoid finding capacity of rat liver nuclei. The effect of aflatoxin B1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [3H]desamethasone-cytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 26 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant. Administration of [3H]dexamethasone to alfatoxin B1 -treated rats produced a similar pattern of glucocorticoid binding distribution in vivo to that observed in vitro. No differences in [3H]dexamethasone-cytoplasmic receptor binding between control and alfatoxin B1 -treated rats were found, whereas nuclear [3H]dexanthasone binding was reduced 34% by alfatoxin B1 -treatment."} {"id": "PMID:181076", "title": "Apparent opposing effects of cyclic AMP and dibutyryl cyclic GMP on the neuronal firing of the blowfly chemo-receptors.", "content": "Cyclic AMP and its dibutyryl derivative inhibit neuronal firing of the labellar sugar sensitive receptor of the blowfly when applied in conjunction with the stimulant sucrose. Furthermore, simultaneous application of aminophylline (phosphodieterase inhibitor) and sucrose or in combination with cyclic AMP caused a similar depression of the sugar receptors response. In contrast, dibutyryl cyclic GMP elicited an increase in sugar receptor firing when applied with sucrose to sugar receptor. Either 5'-AMP or 5'-GMP in combination with sucrose had no discernable effect on the sugar receptors response. Different ratio combinations of cyclic AMP and dibutyryl cyyclic GMP showed the striking inhibitory effect of cyclic AMP upon the dibutyryl cyclic GMP elicited increases in receptor firing frequency. Therefore, it is suggested that these two nucleotides may be mediating different but complimentary aspects of sugar receptor function in a push-pull manner.", "contents": "Apparent opposing effects of cyclic AMP and dibutyryl cyclic GMP on the neuronal firing of the blowfly chemo-receptors. Cyclic AMP and its dibutyryl derivative inhibit neuronal firing of the labellar sugar sensitive receptor of the blowfly when applied in conjunction with the stimulant sucrose. Furthermore, simultaneous application of aminophylline (phosphodieterase inhibitor) and sucrose or in combination with cyclic AMP caused a similar depression of the sugar receptors response. In contrast, dibutyryl cyclic GMP elicited an increase in sugar receptor firing when applied with sucrose to sugar receptor. Either 5'-AMP or 5'-GMP in combination with sucrose had no discernable effect on the sugar receptors response. Different ratio combinations of cyclic AMP and dibutyryl cyyclic GMP showed the striking inhibitory effect of cyclic AMP upon the dibutyryl cyclic GMP elicited increases in receptor firing frequency. Therefore, it is suggested that these two nucleotides may be mediating different but complimentary aspects of sugar receptor function in a push-pull manner."} {"id": "PMID:181077", "title": "Effect of salicyclic acid on gluccorticoid receptor in cultured fibroblasts derived from rat carrageenin granuloma.", "content": "The binding activity of [3H]dexamethasone to the specific receptor was studied in the cytoplasmic fraction of a established fibroblast line derived from rat carrageenin granuloma in culture condition. Specific receptor to dexamethasone was demonstrated. Scatchard analysis revealed a single class of binding sites with a dissociation constant for [3H]dexamethasone of 3.64 - 10(-8) M and a concentration of binding sites of 0.825 pmol per mg cytosol protein. The number of cytoplasmic binding sites per cell was calculated at 1.15 - 10(5). Total binding activity to [3H]dexamethasone of the cytoplasmic fraction was enhanced when the cells were cultured in a medium containing salicylic acid was at 37 degrees C. The maximum enhancement was seen at the concentration of 10(-3)M and in 3h treatment of salicylic acid. This enhancement by salicylic acid was lost when cycloheximide was added to the culture medium at the same time. If salicyclic acid was added to the cell free system, it showed no effect on the binding activity. The other non-steroidal anti-inflammatory drugs; phenylbutazone and indomethacin,also enhanced the total binding activity to [3H]dexamethasone of the cytoplasmic fraction at the concentration of 2 - 10(-5) M and 2 - 10(-7) M, respectively.", "contents": "Effect of salicyclic acid on gluccorticoid receptor in cultured fibroblasts derived from rat carrageenin granuloma. The binding activity of [3H]dexamethasone to the specific receptor was studied in the cytoplasmic fraction of a established fibroblast line derived from rat carrageenin granuloma in culture condition. Specific receptor to dexamethasone was demonstrated. Scatchard analysis revealed a single class of binding sites with a dissociation constant for [3H]dexamethasone of 3.64 - 10(-8) M and a concentration of binding sites of 0.825 pmol per mg cytosol protein. The number of cytoplasmic binding sites per cell was calculated at 1.15 - 10(5). Total binding activity to [3H]dexamethasone of the cytoplasmic fraction was enhanced when the cells were cultured in a medium containing salicylic acid was at 37 degrees C. The maximum enhancement was seen at the concentration of 10(-3)M and in 3h treatment of salicylic acid. This enhancement by salicylic acid was lost when cycloheximide was added to the culture medium at the same time. If salicyclic acid was added to the cell free system, it showed no effect on the binding activity. The other non-steroidal anti-inflammatory drugs; phenylbutazone and indomethacin,also enhanced the total binding activity to [3H]dexamethasone of the cytoplasmic fraction at the concentration of 2 - 10(-5) M and 2 - 10(-7) M, respectively."} {"id": "PMID:181078", "title": "The spin-lattice relaxation times of water associated with early post mortem changes in skeletal muscle.", "content": "We studied the spin-echo signal of muscle water in a large time domain and found that the motion of the nuclear magnetic moment of tissue water cannot be characterized by a single spin-lattice relaxation time (T1). The relaxation time T1B, which is the T1 characterized by those protons with a slower relaxation rate, is influenced by the early post mortem changes in skeletal muscle. T1B increased with time after the tissue was taken from the animal and reached a maximum at 3 h. However, the weighted average of T1 of all water protons (T1A) did not change throughout the time course of the experiments.", "contents": "The spin-lattice relaxation times of water associated with early post mortem changes in skeletal muscle. We studied the spin-echo signal of muscle water in a large time domain and found that the motion of the nuclear magnetic moment of tissue water cannot be characterized by a single spin-lattice relaxation time (T1). The relaxation time T1B, which is the T1 characterized by those protons with a slower relaxation rate, is influenced by the early post mortem changes in skeletal muscle. T1B increased with time after the tissue was taken from the animal and reached a maximum at 3 h. However, the weighted average of T1 of all water protons (T1A) did not change throughout the time course of the experiments."} {"id": "PMID:181079", "title": "Effect of hexoses and mannoheptulose on cyclic AMP accumulation and insulin secretion in rat pancreatic islets.", "content": "The effects of various sugars on the simultaneous release of insulin and accumulation of cyclic AMP were studied in collagenase isolated rat pancreatic islets. D-Glucose stimulated the formation of cyclic AMP at 3 and 60 min of incubation, whether measured by a label incorporation technique, or by the protein kinase binding assay of Gilman. Only D-glucose and D-mannose were able to stimulate insulin release and cyclic [3H]AMP accumulation in the absence of other substrate. D-fructose had a stimulatory effect in the presence of 3.3 mM D-glucose only at a high concentration (33.8 mM), and enhanced the effects of 8.3 mM glucose when added at the concentration of 8.3 mM. D-Galactose was effective only together with 8.3 mM D-glucose. The order of potency of these hexoses, both regarding insulin secretion and cyclic [3H]AMP accumulation, was glucose-mannose-fructose-galactose. L-Glucose and 3-O-methylglucose had no effects at 60 min when incubated together with 8.3 mM D-glucose, whereas at 3 min, 3-O-methylglucose induced a small stimulation of the cyclic [3H]AMP response. D-mannoheptulose and D-glucosamine inhibited the insulin and cyclic [3H]AMP responses to 27.7 mM glucose. Mannoheptulose suppressed completely the glucose effect on cyclic nucleotide accumulation within 90 s. Although under all incubation conditions, the threshold stimulatory or inhibitory concentration of a given agent was identical for insulin release and cyclic [3H]AMP accumulation, these two variables showed quantitative differences in incubations of 60 min, the magnitude of the changes in insulin secretion being larger than that for the cyclic nucleotide. It is suggested that modulation of islet cyclic AMP level is an important step in the transmission of the effect of various sugars on insulin release; however, glucose and possibly other sugars may also enhance insulin release by additional mechanisms not involving the adenylate cyclase-cyclic AMP system of the beta-cell.", "contents": "Effect of hexoses and mannoheptulose on cyclic AMP accumulation and insulin secretion in rat pancreatic islets. The effects of various sugars on the simultaneous release of insulin and accumulation of cyclic AMP were studied in collagenase isolated rat pancreatic islets. D-Glucose stimulated the formation of cyclic AMP at 3 and 60 min of incubation, whether measured by a label incorporation technique, or by the protein kinase binding assay of Gilman. Only D-glucose and D-mannose were able to stimulate insulin release and cyclic [3H]AMP accumulation in the absence of other substrate. D-fructose had a stimulatory effect in the presence of 3.3 mM D-glucose only at a high concentration (33.8 mM), and enhanced the effects of 8.3 mM glucose when added at the concentration of 8.3 mM. D-Galactose was effective only together with 8.3 mM D-glucose. The order of potency of these hexoses, both regarding insulin secretion and cyclic [3H]AMP accumulation, was glucose-mannose-fructose-galactose. L-Glucose and 3-O-methylglucose had no effects at 60 min when incubated together with 8.3 mM D-glucose, whereas at 3 min, 3-O-methylglucose induced a small stimulation of the cyclic [3H]AMP response. D-mannoheptulose and D-glucosamine inhibited the insulin and cyclic [3H]AMP responses to 27.7 mM glucose. Mannoheptulose suppressed completely the glucose effect on cyclic nucleotide accumulation within 90 s. Although under all incubation conditions, the threshold stimulatory or inhibitory concentration of a given agent was identical for insulin release and cyclic [3H]AMP accumulation, these two variables showed quantitative differences in incubations of 60 min, the magnitude of the changes in insulin secretion being larger than that for the cyclic nucleotide. It is suggested that modulation of islet cyclic AMP level is an important step in the transmission of the effect of various sugars on insulin release; however, glucose and possibly other sugars may also enhance insulin release by additional mechanisms not involving the adenylate cyclase-cyclic AMP system of the beta-cell."} {"id": "PMID:181080", "title": "Induction of rat liver phosphoenolpyruvate carbonxykinase (GTP) by cyclic AMP during starvation. The permissive action of glucocorticoids.", "content": "The effect of starvation on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32), and on the response of the enzyme to N6-O2'dibutyryl adenosine 3', 5'-monophosphate was investigated in intact and glucocorticoid-deprived rats. In the liver of intact animals, starvation produced a rapid increase in the concentration of cyclic AMP and a corresponding increase in the activity of phosphoenolpyruvate carboxykinase. The kinetics of both changes were not affected by adrenalectomy. Injection of N6-O2'-dibutyryl adenosine 3', 5'-monophosphate into intact starved rats resulted in an immediate, dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level. Adrenalectomy completely blocked the response of the enzyme to the cyclic nucleotide. Restoration of hydrocortisone to the adrenalectomized animals restored the full N6-I2'dibutyryl adenosine 3', 5'-monophosphate effect after a lag period of 2 h. The physiological significance of these findings is considered. The data are interpreted with regard to the current hypothesis that glucocorticoids promote an increase in translatable phosphoenolpyruvate carboxykinase mRNA, while cyclic AMP enhances the translation of preexisting specific mRNA templates.", "contents": "Induction of rat liver phosphoenolpyruvate carbonxykinase (GTP) by cyclic AMP during starvation. The permissive action of glucocorticoids. The effect of starvation on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32), and on the response of the enzyme to N6-O2'dibutyryl adenosine 3', 5'-monophosphate was investigated in intact and glucocorticoid-deprived rats. In the liver of intact animals, starvation produced a rapid increase in the concentration of cyclic AMP and a corresponding increase in the activity of phosphoenolpyruvate carboxykinase. The kinetics of both changes were not affected by adrenalectomy. Injection of N6-O2'-dibutyryl adenosine 3', 5'-monophosphate into intact starved rats resulted in an immediate, dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level. Adrenalectomy completely blocked the response of the enzyme to the cyclic nucleotide. Restoration of hydrocortisone to the adrenalectomized animals restored the full N6-I2'dibutyryl adenosine 3', 5'-monophosphate effect after a lag period of 2 h. The physiological significance of these findings is considered. The data are interpreted with regard to the current hypothesis that glucocorticoids promote an increase in translatable phosphoenolpyruvate carboxykinase mRNA, while cyclic AMP enhances the translation of preexisting specific mRNA templates."} {"id": "PMID:181081", "title": "Regulation of purine metabolism. Adenylosuccinate synthetase from Novikoff ascites tumor cells.", "content": "Adenylosuccinate synthetase has been partially purified from Novikoff ascites tumor cells. The properties of the protein are quite different from the enzyme from rat liver in that the Km for asparate is higher and the K1 for the feedback inhibitor AMP is also higher. The antibiotic hadacidin has a preferential inhibitory effect on the tumor enzyme. These results suggest that the Novikoff ascites tumor enzyme is less sensitive to normal feedback controls but may be more sensitive to specific antitumor drugs.", "contents": "Regulation of purine metabolism. Adenylosuccinate synthetase from Novikoff ascites tumor cells. Adenylosuccinate synthetase has been partially purified from Novikoff ascites tumor cells. The properties of the protein are quite different from the enzyme from rat liver in that the Km for asparate is higher and the K1 for the feedback inhibitor AMP is also higher. The antibiotic hadacidin has a preferential inhibitory effect on the tumor enzyme. These results suggest that the Novikoff ascites tumor enzyme is less sensitive to normal feedback controls but may be more sensitive to specific antitumor drugs."} {"id": "PMID:181082", "title": "N6,O2'-dibutyryl adenosine 3', 5'-monophosphate-stimulated release of proteoglycans from cultured immature rabbit ear cartilage.", "content": "The stimulatory effects of N6, O2'-dibutyrl adenosine 3',5'-monphosphate on proteoglycan released from immature rabbit ear cartilage were studied in viltro. Cartilage incubayed in medium containing dibutyryl cyclic AMP resulted in a significant increase of proteoglycans released in concentrations above 0.5 mM. Theophylline (1 mM) which did not significantly stimulate proteoglycans released alone, was found to potentiate the action of this nucleotide. ATP, 5'-AMP and butyric acid in the presence of theophylline, did not stimulate proteolgycans released. The addition of protein or RNA synthesis inhibitors depressed proteoglycans released by dibutyryl cyclic AMP and theophylline. Gel chromatogrphic and chemical investigation of the proteoglycans released into the culture media in the presence of dibutylic cyclic AMP indicated a reduction in the proportion of protein associated with these complexes. This result, together with enzyme inhbitor studies, leads us to speculate that the observed action of dibutyryl cyclic AMP on rabbit ear cartilages may be mediated by the neutral proteases.", "contents": "N6,O2'-dibutyryl adenosine 3', 5'-monophosphate-stimulated release of proteoglycans from cultured immature rabbit ear cartilage. The stimulatory effects of N6, O2'-dibutyrl adenosine 3',5'-monphosphate on proteoglycan released from immature rabbit ear cartilage were studied in viltro. Cartilage incubayed in medium containing dibutyryl cyclic AMP resulted in a significant increase of proteoglycans released in concentrations above 0.5 mM. Theophylline (1 mM) which did not significantly stimulate proteoglycans released alone, was found to potentiate the action of this nucleotide. ATP, 5'-AMP and butyric acid in the presence of theophylline, did not stimulate proteolgycans released. The addition of protein or RNA synthesis inhibitors depressed proteoglycans released by dibutyryl cyclic AMP and theophylline. Gel chromatogrphic and chemical investigation of the proteoglycans released into the culture media in the presence of dibutylic cyclic AMP indicated a reduction in the proportion of protein associated with these complexes. This result, together with enzyme inhbitor studies, leads us to speculate that the observed action of dibutyryl cyclic AMP on rabbit ear cartilages may be mediated by the neutral proteases."} {"id": "PMID:181083", "title": "Affinity chromatography of 3 alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni. Use of N,N-dimethylformamide to prevent hydrophobic interactions between the enzyme and the ligand.", "content": "1. The 3alpha-hydroxysteroid: NAD+-oxidoreductase (EC 1.1.1.50) from Pseudomonas testosteroni (ATCC 11996) has been purified by affinity chromatography on Sepharose 4B using glycocholic acid as ligand covalently bound through its carboxyl group to the ethylenediamine spacer. 2. The attachment of the enzyme to the substrate-containing matrix is greatly enhanced by the presence of NAD+ suggesting that this enzyme has a compulsory ordered mechanism where NAD+ binds to the enzyme before the steroid. 3. A NAD+-independent interaction between the enzyme and the ligand was also found. This interaction was mainly hydrophobic and interfered with the NAD+-dependent binding. The NAD+-independent interaction was reduced by N,N-dimethylformamide. 4. By using the affinity column in the presence of 10% N,N-dimethylformamide, highly purified enzyme, as judged from polyacrylamide gel electrophoresis, could be obtained in one step from crude bacterial extracts.", "contents": "Affinity chromatography of 3 alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni. Use of N,N-dimethylformamide to prevent hydrophobic interactions between the enzyme and the ligand. 1. The 3alpha-hydroxysteroid: NAD+-oxidoreductase (EC 1.1.1.50) from Pseudomonas testosteroni (ATCC 11996) has been purified by affinity chromatography on Sepharose 4B using glycocholic acid as ligand covalently bound through its carboxyl group to the ethylenediamine spacer. 2. The attachment of the enzyme to the substrate-containing matrix is greatly enhanced by the presence of NAD+ suggesting that this enzyme has a compulsory ordered mechanism where NAD+ binds to the enzyme before the steroid. 3. A NAD+-independent interaction between the enzyme and the ligand was also found. This interaction was mainly hydrophobic and interfered with the NAD+-dependent binding. The NAD+-independent interaction was reduced by N,N-dimethylformamide. 4. By using the affinity column in the presence of 10% N,N-dimethylformamide, highly purified enzyme, as judged from polyacrylamide gel electrophoresis, could be obtained in one step from crude bacterial extracts."} {"id": "PMID:181084", "title": "On the location of active serines of membrane acetylcholinesterase studied by the ESR method.", "content": "1. An attempt was made to find out the causes of the discrepancy between the ESR spectra of membrane acetylcholinesterase (EC 3.1.1.7) obtained by Morrisett and co-workers and those obtained by the present authors. 2. In order to see whether the discrepancy was due to the different spin-labeling procedures, the same membrane acetylcholinesterase preparations were spin-labeled with the same compound, using the two different spin-labeling procedures. The enzyme activity was determined with pH-static titration and the ESR spectra recorded. 3. It was found that after spin-labeling according to Morrisett and co-workers, there were from 10-100 times more spin-label molecules bound to the enzyme preparations than there were active serines in them. 4. Using the method of Morrisett and co-workers, the majority of spin-label molecules was found to be bound to sites outside the active serines whereas the spin-labeling procedures of the present authors proved to be selective for active serines; the discrepancy in ESR spectra is explained.", "contents": "On the location of active serines of membrane acetylcholinesterase studied by the ESR method. 1. An attempt was made to find out the causes of the discrepancy between the ESR spectra of membrane acetylcholinesterase (EC 3.1.1.7) obtained by Morrisett and co-workers and those obtained by the present authors. 2. In order to see whether the discrepancy was due to the different spin-labeling procedures, the same membrane acetylcholinesterase preparations were spin-labeled with the same compound, using the two different spin-labeling procedures. The enzyme activity was determined with pH-static titration and the ESR spectra recorded. 3. It was found that after spin-labeling according to Morrisett and co-workers, there were from 10-100 times more spin-label molecules bound to the enzyme preparations than there were active serines in them. 4. Using the method of Morrisett and co-workers, the majority of spin-label molecules was found to be bound to sites outside the active serines whereas the spin-labeling procedures of the present authors proved to be selective for active serines; the discrepancy in ESR spectra is explained."} {"id": "PMID:181085", "title": "A kinetic analysis of the dephosphorylation, by bovine spleen phosphoprotein phosphatase (EC 3.1.3.16) of a phosphopeptide derived from beta-casein.", "content": "A peptide containing the four closely grouped phosphoseryl residues present in beta-casein has been enzymatically dephosphorylated with bovine spleen phosphoprotein phosphatase (EC 3.1.3.16). The course of the dephosphorylation reaction has been followed by cellulose acetate electrophoresis and the amount of partially phosphorylated peptides present at each stage quantified by the same method. The phosphate groups are shown to be removed in a sequential manner and the rate constants for each stage of the dephosphorylation have been computed from the data obtained. The rate constants indicate that interaction in the intact peptide results in an enhancement of the activity of the phosphoseryl cluster.", "contents": "A kinetic analysis of the dephosphorylation, by bovine spleen phosphoprotein phosphatase (EC 3.1.3.16) of a phosphopeptide derived from beta-casein. A peptide containing the four closely grouped phosphoseryl residues present in beta-casein has been enzymatically dephosphorylated with bovine spleen phosphoprotein phosphatase (EC 3.1.3.16). The course of the dephosphorylation reaction has been followed by cellulose acetate electrophoresis and the amount of partially phosphorylated peptides present at each stage quantified by the same method. The phosphate groups are shown to be removed in a sequential manner and the rate constants for each stage of the dephosphorylation have been computed from the data obtained. The rate constants indicate that interaction in the intact peptide results in an enhancement of the activity of the phosphoseryl cluster."} {"id": "PMID:181086", "title": "Biochemical assay by immobilized enzymes and a mass spectrometer.", "content": "By counting the volatile molecules produced by an immobilized-enzyme catalyzed reaction which is interfaced to a mass spectrometer via a semi-permeable membrane, a general approach to biochemical measurement and detection is obtained which offers the potential of high sensitivity, specificity and speed. In combination with molecule microscopy, this method should allow, for example, a mapping of suitable enzyme distributions in non-stained and non-fixed tissue slices. Immobilized urease (urea amidohyrdrolase, EC 3.5.1.5) was used to assay urea using CO2 as the volatile product, and alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) was used to assay NADH using ethanol as the volatile product.", "contents": "Biochemical assay by immobilized enzymes and a mass spectrometer. By counting the volatile molecules produced by an immobilized-enzyme catalyzed reaction which is interfaced to a mass spectrometer via a semi-permeable membrane, a general approach to biochemical measurement and detection is obtained which offers the potential of high sensitivity, specificity and speed. In combination with molecule microscopy, this method should allow, for example, a mapping of suitable enzyme distributions in non-stained and non-fixed tissue slices. Immobilized urease (urea amidohyrdrolase, EC 3.5.1.5) was used to assay urea using CO2 as the volatile product, and alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) was used to assay NADH using ethanol as the volatile product."} {"id": "PMID:181087", "title": "Dinucleosidasetetraphosphatase in rat liver and Artemia salina.", "content": "A comparative study of an enzymatic activity present in Artemia salina and rat liver which specifically splits dinucleoside tetraphosphates is presented. All the purine and pyrimidine dinucleoside tetraphosphates tested, i.e. diadenosine, diguanosine, dixanthosine and diuridine tetraphosphates, were substrates of both enzymes with similar maximum velocities and Km values, (around 10 muM). The inhibition by nucleotides of the enzyme from the two sources is also similar. Particularly relevant is the strong inhibition caused by nucleoside tetraphosphates which have Ki values in the nanomolar range. The Artemia enzyme has a slightly lower molecular weight (17 500) than the liver enzyme (21 000) and is more resistant to acidic pH. Based on previous findings, the enzyme from Artemia salina was named diguanosinetetraphosphatase (EC 3.6.1.17) by the Enzyme Commission. The results presented in this paper show that the liver and Artemia enzymes are similar, and we propose to name this enzyme as dinucleosidetetraphosphatase or dinucleoside-tetraphosphate nucleotidehydrolase.", "contents": "Dinucleosidasetetraphosphatase in rat liver and Artemia salina. A comparative study of an enzymatic activity present in Artemia salina and rat liver which specifically splits dinucleoside tetraphosphates is presented. All the purine and pyrimidine dinucleoside tetraphosphates tested, i.e. diadenosine, diguanosine, dixanthosine and diuridine tetraphosphates, were substrates of both enzymes with similar maximum velocities and Km values, (around 10 muM). The inhibition by nucleotides of the enzyme from the two sources is also similar. Particularly relevant is the strong inhibition caused by nucleoside tetraphosphates which have Ki values in the nanomolar range. The Artemia enzyme has a slightly lower molecular weight (17 500) than the liver enzyme (21 000) and is more resistant to acidic pH. Based on previous findings, the enzyme from Artemia salina was named diguanosinetetraphosphatase (EC 3.6.1.17) by the Enzyme Commission. The results presented in this paper show that the liver and Artemia enzymes are similar, and we propose to name this enzyme as dinucleosidetetraphosphatase or dinucleoside-tetraphosphate nucleotidehydrolase."} {"id": "PMID:181088", "title": "Lysyl hydroxylase. Further purification and characterization of the enzyme from chick embryos and chick embryo cartilage.", "content": "A purification of up to 4000-fold is reported for lysyl hydroxylase (EC 1.14.11.4) from extract of chick-embryo homogenate and one of about 300-fold from extract of chick-embryo cartilage. Multiple forms of the enzyme were observed during purification from whole chick embryos. In gel filtration the elution positions of the two main forms corresponded to average molecular weights of about 580000 and 220000. These two forms could also be clearly separated in hydroxyapatite chromatography. In addition, some enzyme activity was always eluted between the two main peaks both in gel filtration and in hydroxyapatite chromatography. The presence of the two main forms was also observed when purifying enzyme from chick embryo cartilage. Both forms of the enzyme hydroxylated lysine in arginine-rich histone, which does not contain any -X-Lys-Gly- sequence. No difference was found between the enzyme from whole chick embryos and from chick embryo cartilage in this respect. Lysyl hydroxylase was found to have affinity for concanavalin A, indicating the presence of some carbohydrate residues in the enzyme molecule. Lysyl and prolyl hydroxylase activities increased when the chick embryo homogenate was assayed in the presence of lysolecithin. Preincubation of the homogenate either with lysolecithin or with Triton X-100 increased lysyl hydroxylase activity in homogenate, and in the 1500 x g and 150000 x g supernatants, suggesting that the increase in the enzyme activity was due to liberation of the enzyme from the membranes. Divalent cations were found to inhibit the activity of lysyl and prolyl hydroxylases in vitro. An inhibition of about 50% was achieved with 15 mM calcium 60 muM copper and 3 muM zinc concentrations. The mode of inhibition was tested with Cu2+, and was found to be competitive with Fe2+.", "contents": "Lysyl hydroxylase. Further purification and characterization of the enzyme from chick embryos and chick embryo cartilage. A purification of up to 4000-fold is reported for lysyl hydroxylase (EC 1.14.11.4) from extract of chick-embryo homogenate and one of about 300-fold from extract of chick-embryo cartilage. Multiple forms of the enzyme were observed during purification from whole chick embryos. In gel filtration the elution positions of the two main forms corresponded to average molecular weights of about 580000 and 220000. These two forms could also be clearly separated in hydroxyapatite chromatography. In addition, some enzyme activity was always eluted between the two main peaks both in gel filtration and in hydroxyapatite chromatography. The presence of the two main forms was also observed when purifying enzyme from chick embryo cartilage. Both forms of the enzyme hydroxylated lysine in arginine-rich histone, which does not contain any -X-Lys-Gly- sequence. No difference was found between the enzyme from whole chick embryos and from chick embryo cartilage in this respect. Lysyl hydroxylase was found to have affinity for concanavalin A, indicating the presence of some carbohydrate residues in the enzyme molecule. Lysyl and prolyl hydroxylase activities increased when the chick embryo homogenate was assayed in the presence of lysolecithin. Preincubation of the homogenate either with lysolecithin or with Triton X-100 increased lysyl hydroxylase activity in homogenate, and in the 1500 x g and 150000 x g supernatants, suggesting that the increase in the enzyme activity was due to liberation of the enzyme from the membranes. Divalent cations were found to inhibit the activity of lysyl and prolyl hydroxylases in vitro. An inhibition of about 50% was achieved with 15 mM calcium 60 muM copper and 3 muM zinc concentrations. The mode of inhibition was tested with Cu2+, and was found to be competitive with Fe2+."} {"id": "PMID:181089", "title": "Steady-state kinetics of high molecular weight (type-I) NADH dehydrogenase.", "content": "(1) Studies of the steady-state kinetics of the NADH dehydrogenase activity of Complex I (NADH: Q oxidoreductase) revealed that the reaction mechanism with the one-electron acceptor ferricyanide or the two-electron acceptor 2,6-dichloro-indophenol is ping pong bi bi, with double substrate inhibition. NADH inhibits the reaction of the reduced form of the flavoprotein with the acceptors, and the acceptors prevent NADH from reacting with the oxidized form. This implies that both NADH and acceptors react with the same site on NADH dehydrogenase. (2) The velocity at infinite NADH and acceptor concentrations (corrected for the double substrate inhibition) is much larger with ferricyanide than with the indophenol. It is concluded that the latter binds to the reduced enzyme. Thus, with ferricyanide the rate constant measured refers to the dissociation of bound NAD+ from the reduced enzyme (k2) and with the indophenol to the rate constant of oxidation of reduced enzyme by bound acceptor (k4). The latter value is not an estimate for the situation in vivo, where ubiquinone is the acceptor. (3) The rate constant of the dissociation of bound NAD+ from the reduced enzyme (k2) increases with pH. It is suggested that an ionizing group on the enzyme is involved in the dissociation. (4) After extraction of ubiquinone from Complex I with pentane curve relating activity at infinite ferricyanide concentration to NADH concentration changes from hyperbolic to sigmoidal. The hyperbolic curve is restored by reincorporating ubiquinone. It is concluded that ubiquinone is an effector for NADH dehydrogenase.", "contents": "Steady-state kinetics of high molecular weight (type-I) NADH dehydrogenase. (1) Studies of the steady-state kinetics of the NADH dehydrogenase activity of Complex I (NADH: Q oxidoreductase) revealed that the reaction mechanism with the one-electron acceptor ferricyanide or the two-electron acceptor 2,6-dichloro-indophenol is ping pong bi bi, with double substrate inhibition. NADH inhibits the reaction of the reduced form of the flavoprotein with the acceptors, and the acceptors prevent NADH from reacting with the oxidized form. This implies that both NADH and acceptors react with the same site on NADH dehydrogenase. (2) The velocity at infinite NADH and acceptor concentrations (corrected for the double substrate inhibition) is much larger with ferricyanide than with the indophenol. It is concluded that the latter binds to the reduced enzyme. Thus, with ferricyanide the rate constant measured refers to the dissociation of bound NAD+ from the reduced enzyme (k2) and with the indophenol to the rate constant of oxidation of reduced enzyme by bound acceptor (k4). The latter value is not an estimate for the situation in vivo, where ubiquinone is the acceptor. (3) The rate constant of the dissociation of bound NAD+ from the reduced enzyme (k2) increases with pH. It is suggested that an ionizing group on the enzyme is involved in the dissociation. (4) After extraction of ubiquinone from Complex I with pentane curve relating activity at infinite ferricyanide concentration to NADH concentration changes from hyperbolic to sigmoidal. The hyperbolic curve is restored by reincorporating ubiquinone. It is concluded that ubiquinone is an effector for NADH dehydrogenase."} {"id": "PMID:181090", "title": "Steady-state kinetics of low molecular weight (type-II) NADH dehydrogenase.", "content": "(1) The steady-state kinetics of the NADH dehydrogenase activity of Type-II (low molecular weight) NADH dehydrogenase with the acceptors ferricyanide, cytochrome c and 2,6-dichloroindophenol are consistent with the simultaneous operation of an ordered and a ping-pong mechanism. Thus, depending on the acceptor concentration, the reduced enzyme is preferentially oxidized before or after NAD+ disociates from it. (2) The acceptors are able to oxidize the reduced enzyme and its NAD+ complex equally well. In contrast to the kinetics of the Type-I (high molecular weight) enzyme, double substrate inhibition is not found, implying that the site of oxidation of the reduced enzyme by acceptors and the NADH-binding site are remote. (3) With the indophenol, in the concentration range measured, the ordered mechanism is mainly operative. At infinite NADH and acceptor concentrations the rate constant of the reduction of enzyme by bound NADH is measured. (4) With ferricyanide and cytochrome c, in the concentration range measured, erroneous conclusions may be drawn from extrapolations owing to the fact that extrapolated lines in double-reciprocal plots of turnover number against acceptor concentration, at different NADH concentrations, intersect in the third quadrant. A method is described that allows the extrapolation of these data to zero acceptor concentrations. (5) The relation between activity and NADH concentration is sigmoidal (h = 2.0) with ferricyanide or cytochrome c as acceptor, but hyperbolic with 2,6-dichloroindophenol. The latter is also an inhibitor, competitive with respect to NADH. It is concluded that this two-electron acceptor, like ubiquinone, acts as an allosteric effector. (6) Type II is isolated from Type I without gross changes in tertiary structure, as judged by the unaltered rate constants of dissociation of NADH (k-1) and NAD+ (k4) and association of NADH (k1). (7) Type II differs from Type I in two respects, (a) The accessibility of the acceptors is greater by at least two orders of magnitude (k3). (b) The redox potential of the prosthetic group FMN is 120 mV less, as judged by a drop in the value of k2 by four orders of magnitude. It is suggested that one or more of the iron-sulphur proteins present in Type-I but lacking in Type-II dehydrogenase functions as an effector, regulating the redox potential of the FMN.", "contents": "Steady-state kinetics of low molecular weight (type-II) NADH dehydrogenase. (1) The steady-state kinetics of the NADH dehydrogenase activity of Type-II (low molecular weight) NADH dehydrogenase with the acceptors ferricyanide, cytochrome c and 2,6-dichloroindophenol are consistent with the simultaneous operation of an ordered and a ping-pong mechanism. Thus, depending on the acceptor concentration, the reduced enzyme is preferentially oxidized before or after NAD+ disociates from it. (2) The acceptors are able to oxidize the reduced enzyme and its NAD+ complex equally well. In contrast to the kinetics of the Type-I (high molecular weight) enzyme, double substrate inhibition is not found, implying that the site of oxidation of the reduced enzyme by acceptors and the NADH-binding site are remote. (3) With the indophenol, in the concentration range measured, the ordered mechanism is mainly operative. At infinite NADH and acceptor concentrations the rate constant of the reduction of enzyme by bound NADH is measured. (4) With ferricyanide and cytochrome c, in the concentration range measured, erroneous conclusions may be drawn from extrapolations owing to the fact that extrapolated lines in double-reciprocal plots of turnover number against acceptor concentration, at different NADH concentrations, intersect in the third quadrant. A method is described that allows the extrapolation of these data to zero acceptor concentrations. (5) The relation between activity and NADH concentration is sigmoidal (h = 2.0) with ferricyanide or cytochrome c as acceptor, but hyperbolic with 2,6-dichloroindophenol. The latter is also an inhibitor, competitive with respect to NADH. It is concluded that this two-electron acceptor, like ubiquinone, acts as an allosteric effector. (6) Type II is isolated from Type I without gross changes in tertiary structure, as judged by the unaltered rate constants of dissociation of NADH (k-1) and NAD+ (k4) and association of NADH (k1). (7) Type II differs from Type I in two respects, (a) The accessibility of the acceptors is greater by at least two orders of magnitude (k3). (b) The redox potential of the prosthetic group FMN is 120 mV less, as judged by a drop in the value of k2 by four orders of magnitude. It is suggested that one or more of the iron-sulphur proteins present in Type-I but lacking in Type-II dehydrogenase functions as an effector, regulating the redox potential of the FMN."} {"id": "PMID:181091", "title": "Electrochemical characterization of immobilized NAD+.", "content": "Nicotinamide adenine dinucleotide (NAD+) has been covalently attached to alginic acid using carbodiimide coupling, thereby producing a macromolecular adduct of NAD, which can be rendered either soluble or insoluble by adjustment of pH. It was found that this NAD+-alginic acid complex was enzymatically active, and also that the oxidized form could be electrochemically reduced without loss in enzymatic activity. This NAD+ adduct has now also been polarographically characterized as to its two-step reduction waves, which are slightly shifted toward more cathodic potential as compared to free NAD+. When controlled electrolysis was conducted to reduce the bound NAD+ at the cathode, the NADH so formed by electrochemical action was found to be again oxidizable either enzymatically or electrochemically without loss in co-enzymatic function. The NADH adduct produced by electrochemical reduction of the NAD+ adduct has also been characterized by voltammetry.", "contents": "Electrochemical characterization of immobilized NAD+. Nicotinamide adenine dinucleotide (NAD+) has been covalently attached to alginic acid using carbodiimide coupling, thereby producing a macromolecular adduct of NAD, which can be rendered either soluble or insoluble by adjustment of pH. It was found that this NAD+-alginic acid complex was enzymatically active, and also that the oxidized form could be electrochemically reduced without loss in enzymatic activity. This NAD+ adduct has now also been polarographically characterized as to its two-step reduction waves, which are slightly shifted toward more cathodic potential as compared to free NAD+. When controlled electrolysis was conducted to reduce the bound NAD+ at the cathode, the NADH so formed by electrochemical action was found to be again oxidizable either enzymatically or electrochemically without loss in co-enzymatic function. The NADH adduct produced by electrochemical reduction of the NAD+ adduct has also been characterized by voltammetry."} {"id": "PMID:181092", "title": "Flash photolysis-electron spin resonance studies of photosystem I. A fast reduction of component of P-700+.", "content": "A 300 mus decay component of ESR Signal I (P-700+) in chloroplasts is observed following a 10 mus actinic xenon flash. This transient is inhibited by treatments which block electron transfer from Photosystem II to Photosystem I (e.g. 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), KCN and HgCl2). The fast transient reduction of P-700+ can be restored in the case of DCMU or DBMIB inhibition by addition of an electron donor couple (2,6-dichlorophenol indophenol (Cl2Ind)/ascorbate) which supplies electrons to cytochrome f. However, this donor couple is inefficient in restoring electron transport in chloroplasts which have been inhibited with the plastocyanin inactivators, KCN and HgCl2. Oxidation-reduction measurements reveal that the fast P-700+ reduction component reflects electron transfer from a component with Em = 375 +/- 10 mV (pH = 7.5). These data suggest the assignment of the 300-mus decay kinetics to electron transfer from cytochrome f (Fe2+) to P-700+, thus confirming the recent observations of Haehnel et al. (Z. Naturforsch. 26b, 1171-1174 (1971)).", "contents": "Flash photolysis-electron spin resonance studies of photosystem I. A fast reduction of component of P-700+. A 300 mus decay component of ESR Signal I (P-700+) in chloroplasts is observed following a 10 mus actinic xenon flash. This transient is inhibited by treatments which block electron transfer from Photosystem II to Photosystem I (e.g. 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), KCN and HgCl2). The fast transient reduction of P-700+ can be restored in the case of DCMU or DBMIB inhibition by addition of an electron donor couple (2,6-dichlorophenol indophenol (Cl2Ind)/ascorbate) which supplies electrons to cytochrome f. However, this donor couple is inefficient in restoring electron transport in chloroplasts which have been inhibited with the plastocyanin inactivators, KCN and HgCl2. Oxidation-reduction measurements reveal that the fast P-700+ reduction component reflects electron transfer from a component with Em = 375 +/- 10 mV (pH = 7.5). These data suggest the assignment of the 300-mus decay kinetics to electron transfer from cytochrome f (Fe2+) to P-700+, thus confirming the recent observations of Haehnel et al. (Z. Naturforsch. 26b, 1171-1174 (1971))."} {"id": "PMID:181094", "title": "Glycerokinase activity and lipolysis regulation in brown adipose tissue of cold acclimated rats.", "content": "Glycerol release by brown adipocytes from constant cold adapted rats was not stimulated by norepinephrine. On the contrary, the release was stimulated in rats adapted to a nycthemeral fluctuatiing temperature from 5 degrees to 28 degrees C. Glycerokinase activity was greatly increased in brown adipose tissue by cold adptation ; there was no change in the liver. However this increased activity cannot entirely explain the lack of norepinephrine stimulation of glycerol release in the brown adipose tissue of cold adapted rats.", "contents": "Glycerokinase activity and lipolysis regulation in brown adipose tissue of cold acclimated rats. Glycerol release by brown adipocytes from constant cold adapted rats was not stimulated by norepinephrine. On the contrary, the release was stimulated in rats adapted to a nycthemeral fluctuatiing temperature from 5 degrees to 28 degrees C. Glycerokinase activity was greatly increased in brown adipose tissue by cold adptation ; there was no change in the liver. However this increased activity cannot entirely explain the lack of norepinephrine stimulation of glycerol release in the brown adipose tissue of cold adapted rats."} {"id": "PMID:181097", "title": "Association between macrophage activity and serum haptoglobin levels.", "content": "Serum haptoglobin is elevated by treatment of mice with thioglycollate, B.C.G. or silica. Haptoglobin concentrations were followed for a two week period following treatment and were found to correlate with the known effect of the stimulants upon macrophage activity. The numbers and characteristics of peritoneal exudate cells present following intraperitoneal thioglycollate inoculation suggest a relationship between phagocytic activity and serum haptoglobin levels and support the idea that serum haptoglobin levels may be controlled by mediators released during the process of phagocytosis.", "contents": "Association between macrophage activity and serum haptoglobin levels. Serum haptoglobin is elevated by treatment of mice with thioglycollate, B.C.G. or silica. Haptoglobin concentrations were followed for a two week period following treatment and were found to correlate with the known effect of the stimulants upon macrophage activity. The numbers and characteristics of peritoneal exudate cells present following intraperitoneal thioglycollate inoculation suggest a relationship between phagocytic activity and serum haptoglobin levels and support the idea that serum haptoglobin levels may be controlled by mediators released during the process of phagocytosis."} {"id": "PMID:181098", "title": "Temperature dependence of ESR spectra of spin-labelled met-hemoglobin.", "content": "The maleimide spin-label, firmly fixed to the protein, was used to study conformation changes of various met-hemoglobin derivatives. The temperature dependence of the rotational correlation time shows a distinct conformation change in aquomet-hemoglobin at about 25 degrees C. The other met-hemoglobin derivatives studied (fluoro-, cyano-, aquomet-complexed with inositol hexaphosphate) and carbonmonoxy-hemoglobin exhibit no conformation changes in the temperature range from 0-50 degrees C.", "contents": "Temperature dependence of ESR spectra of spin-labelled met-hemoglobin. The maleimide spin-label, firmly fixed to the protein, was used to study conformation changes of various met-hemoglobin derivatives. The temperature dependence of the rotational correlation time shows a distinct conformation change in aquomet-hemoglobin at about 25 degrees C. The other met-hemoglobin derivatives studied (fluoro-, cyano-, aquomet-complexed with inositol hexaphosphate) and carbonmonoxy-hemoglobin exhibit no conformation changes in the temperature range from 0-50 degrees C."} {"id": "PMID:181099", "title": "[Mechanisms of transmission of excitation grnerated in the orbito-frontal cortex].", "content": "Experiments carried out on cats showed that interhemispheric generalization of strychnine spasmodic potentials from the orbito-frontal cortex were mainly brought about by the callosal pathway. In contrast to other projection and association zones of the cortex only the frontal portion of the corpus callosum (the rostrum) and not the whole corpus took part in transmitting strychnine commissures. The results of investigations carried out were consistent with the general conception of the principle of the determining dispatch station (DDS) in the nervous system integration activity. These results reveal that the appearance of the DDS induces secondary excitation foci which fully reproduce tha work regimen of the DDS. Switching of such \"mirror\" foci representing \"the destination stations\" from the DDS influence led to the elimination of the activity induced in them.", "contents": "[Mechanisms of transmission of excitation grnerated in the orbito-frontal cortex]. Experiments carried out on cats showed that interhemispheric generalization of strychnine spasmodic potentials from the orbito-frontal cortex were mainly brought about by the callosal pathway. In contrast to other projection and association zones of the cortex only the frontal portion of the corpus callosum (the rostrum) and not the whole corpus took part in transmitting strychnine commissures. The results of investigations carried out were consistent with the general conception of the principle of the determining dispatch station (DDS) in the nervous system integration activity. These results reveal that the appearance of the DDS induces secondary excitation foci which fully reproduce tha work regimen of the DDS. Switching of such \"mirror\" foci representing \"the destination stations\" from the DDS influence led to the elimination of the activity induced in them."} {"id": "PMID:181100", "title": "[Cyclic adenosine-3',5'-monophosphate content of the brain in conditions of extreme stimulation].", "content": "The content of brain cAMP was investigated under conditions of electric stimulation of immobilized rats which resulted in the development of reflex dystrophies of the internal organs. There was found a pronounced decrease in the amount of cAMP in the rat brain which developed 15 minutes after the beginning of extreme stimulation and remaained at the same low level for 3 hours after the electrical irritation. Reduction of the cAMP level was probably connected with noradrenaline and other biologically-active amine deficiency in the brain under conditions of extreme stimulation.", "contents": "[Cyclic adenosine-3',5'-monophosphate content of the brain in conditions of extreme stimulation]. The content of brain cAMP was investigated under conditions of electric stimulation of immobilized rats which resulted in the development of reflex dystrophies of the internal organs. There was found a pronounced decrease in the amount of cAMP in the rat brain which developed 15 minutes after the beginning of extreme stimulation and remaained at the same low level for 3 hours after the electrical irritation. Reduction of the cAMP level was probably connected with noradrenaline and other biologically-active amine deficiency in the brain under conditions of extreme stimulation."} {"id": "PMID:181101", "title": "[Adrenaline-induced release from thrombocytes of beta-lipoprotein, alkaline phosphatase and 5'-nucleotidase].", "content": "Platelet aggregation induced by adrenaline is accompanied by release of beta-lipoprotein, alkaline phosphatase, 5'-nucleotidase and factor 3. Electrophoretic mobility of platelet alkaline phosphatase was the same as that of beta-lipoprotein. This suggest that beta-lipoprotein, alkaline phosphatase and 5'-nucleotidase are structural components of platelet compounds which possess factor 3 activity.", "contents": "[Adrenaline-induced release from thrombocytes of beta-lipoprotein, alkaline phosphatase and 5'-nucleotidase]. Platelet aggregation induced by adrenaline is accompanied by release of beta-lipoprotein, alkaline phosphatase, 5'-nucleotidase and factor 3. Electrophoretic mobility of platelet alkaline phosphatase was the same as that of beta-lipoprotein. This suggest that beta-lipoprotein, alkaline phosphatase and 5'-nucleotidase are structural components of platelet compounds which possess factor 3 activity."} {"id": "PMID:181102", "title": "[Change in the mitotic activity of hepatocytes and resorption of necrotic areas in the formation of liver cirrhosis].", "content": "Cirrhosis of the liver was induced in rats weighing 120--140 g by CCl4 administration for a period of 2 months. Iodated oil, which caused emboly of the portal vein branches and foci of necrosis in the heptic tissue, was administered through the spleen to experimental and intact animals. The volume of necrotic foci, and also the mitotic actinity of hepatites were determined. Necrotic foci resolved more rapidly in cirrhosis of the liver. An increase of mitotic index of the second day after the administration of iodated oil was more significant in control rats.", "contents": "[Change in the mitotic activity of hepatocytes and resorption of necrotic areas in the formation of liver cirrhosis]. Cirrhosis of the liver was induced in rats weighing 120--140 g by CCl4 administration for a period of 2 months. Iodated oil, which caused emboly of the portal vein branches and foci of necrosis in the heptic tissue, was administered through the spleen to experimental and intact animals. The volume of necrotic foci, and also the mitotic actinity of hepatites were determined. Necrotic foci resolved more rapidly in cirrhosis of the liver. An increase of mitotic index of the second day after the administration of iodated oil was more significant in control rats."} {"id": "PMID:181103", "title": "[Effect of coniophage decomposition products on the biological activity of fibroblasts].", "content": "Cytochemical studies showed that destroyed coinophages, which phagocytized cytoxic and fibrogenic quartz dust, activated the synthetic function of rat fibroblasts when added to the culture medium. Inert talcum dust used under similar experimental conditions failed to produce any noticable changes in comparison with control studies.", "contents": "[Effect of coniophage decomposition products on the biological activity of fibroblasts]. Cytochemical studies showed that destroyed coinophages, which phagocytized cytoxic and fibrogenic quartz dust, activated the synthetic function of rat fibroblasts when added to the culture medium. Inert talcum dust used under similar experimental conditions failed to produce any noticable changes in comparison with control studies."} {"id": "PMID:181104", "title": "Changes in the contractile response of arteires and veins from hypertensive rabbits to sympathetic nerve activity: assessment of some postsynaptic influences.", "content": "Contractile responses to field stimulation of intramural nerves of arteries and veins taken from rabbits made hypertensive by partial constriction of the abdominal aorta have been related to the carotid artery pressure. The increase in contraction of cephalic and short saphenous veins with rise in carotid artery pressure can be accounted for by an increase in sensitivity of the alpha-adrenergic receptor. The neurogenic contraction of the ear artery increased with carotid artery pressure rise. Changes in some of the extraneuronal factors that influence transmitter distribution and disposition in the tunica media were examined. In hypertensive animals, the percentage of released adrenergic transmitter entering the vessel wall might be expected to decrease due to an increase in medial thickness. However, this percentage was not significantly altered in the ear artery probably due, in part, to a concomitant increase in medial permeability to the transmitter. Extraneuronal transmitter disposition factors, i.e. extraneuronal uptake, monoamine oxidase, and catechol-O-methyltransferase activity are directly related to the wet weight of the vessel wall. Thus, their contribution to transmitter disposition would be expected to increase with increase in vessel wall thickness and tend to reduce the response to sympathetic activity. As the contractile response increased in the hypertensive vessels despite such changes, the increase in effector cell mass and density of neuronal terminal plexus, shown previously to increase with hypertension, are more important than these other considerations.", "contents": "Changes in the contractile response of arteires and veins from hypertensive rabbits to sympathetic nerve activity: assessment of some postsynaptic influences. Contractile responses to field stimulation of intramural nerves of arteries and veins taken from rabbits made hypertensive by partial constriction of the abdominal aorta have been related to the carotid artery pressure. The increase in contraction of cephalic and short saphenous veins with rise in carotid artery pressure can be accounted for by an increase in sensitivity of the alpha-adrenergic receptor. The neurogenic contraction of the ear artery increased with carotid artery pressure rise. Changes in some of the extraneuronal factors that influence transmitter distribution and disposition in the tunica media were examined. In hypertensive animals, the percentage of released adrenergic transmitter entering the vessel wall might be expected to decrease due to an increase in medial thickness. However, this percentage was not significantly altered in the ear artery probably due, in part, to a concomitant increase in medial permeability to the transmitter. Extraneuronal transmitter disposition factors, i.e. extraneuronal uptake, monoamine oxidase, and catechol-O-methyltransferase activity are directly related to the wet weight of the vessel wall. Thus, their contribution to transmitter disposition would be expected to increase with increase in vessel wall thickness and tend to reduce the response to sympathetic activity. As the contractile response increased in the hypertensive vessels despite such changes, the increase in effector cell mass and density of neuronal terminal plexus, shown previously to increase with hypertension, are more important than these other considerations."} {"id": "PMID:181110", "title": "Indomethacin-induced alterations in corticosteroid and prostaglandin release by isolated adrenocortical cells of the cat.", "content": "1 The effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin-dispersed cat adrenocortical cells were investigated. 2 Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)-evoked prostaglandin and steroid release, whereas higher concentrations depressed both responses to ACTH. The steroidogenic response to exogenous prostaglandin E2 was not markedly altered over a wide range of indomethacin concentrations. 3 Indomethacin enhanced basal steroid release but did not enhance basal prostaglandin E or F release. 4 5,8,11,14-Eicosatetraynoic acid (ETA) elicited a concentration-dependent inhibition of ACTH-induced steroid release, but had little effect on prostaglandin E2-induced steroid release. A high concentration of ETA inhibited prostaglandin E and F release. 5 These data are discussed in relation to the concept that prostaglandins provide a critical link in ACTH-induced corticosteroidogenesis.", "contents": "Indomethacin-induced alterations in corticosteroid and prostaglandin release by isolated adrenocortical cells of the cat. 1 The effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin-dispersed cat adrenocortical cells were investigated. 2 Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)-evoked prostaglandin and steroid release, whereas higher concentrations depressed both responses to ACTH. The steroidogenic response to exogenous prostaglandin E2 was not markedly altered over a wide range of indomethacin concentrations. 3 Indomethacin enhanced basal steroid release but did not enhance basal prostaglandin E or F release. 4 5,8,11,14-Eicosatetraynoic acid (ETA) elicited a concentration-dependent inhibition of ACTH-induced steroid release, but had little effect on prostaglandin E2-induced steroid release. A high concentration of ETA inhibited prostaglandin E and F release. 5 These data are discussed in relation to the concept that prostaglandins provide a critical link in ACTH-induced corticosteroidogenesis."} {"id": "PMID:181111", "title": "Van Buchem's disease (hyperostosis corticalis generalisata)", "content": "The features of Van Buchem's disease are described, affecting six members of one family, spanning three generations of ages from 7 to 64 years.", "contents": "Van Buchem's disease (hyperostosis corticalis generalisata). The features of Van Buchem's disease are described, affecting six members of one family, spanning three generations of ages from 7 to 64 years."} {"id": "PMID:181112", "title": "A new stannous agent kit for labelling red blood cells with 99TCM and its clinical application.", "content": "99Tcm is chosen for labelling erythrocytes for vascular imaging to take advantage of the physical properties of the radionuclide. A new procedure is described which belongs to the category of pre-treatment methods using a kit. Stannous pyrophosphate is the specific reducing reagent. The technique is easier than already published methods: it consists of adding the above reagent to 2 ml. of heparinized blood, waiting five minutes and discarding the serum after centrifugation, then adding the radioactivity required as 99TcmO4. Labelling yield is superior to 95 per cent. The influence of technetium concentration of the pertechnetate solution on the labeling yield is evaluated and compensated by a slight adjustment of tin concentration when necessary. In vitro and in vivo stability studies show that 99Tcm-labelled red cells are suitable for determination of red cell volume, spleen and placental imaging, particularly in emergencies and in paediatrics.", "contents": "A new stannous agent kit for labelling red blood cells with 99TCM and its clinical application. 99Tcm is chosen for labelling erythrocytes for vascular imaging to take advantage of the physical properties of the radionuclide. A new procedure is described which belongs to the category of pre-treatment methods using a kit. Stannous pyrophosphate is the specific reducing reagent. The technique is easier than already published methods: it consists of adding the above reagent to 2 ml. of heparinized blood, waiting five minutes and discarding the serum after centrifugation, then adding the radioactivity required as 99TcmO4. Labelling yield is superior to 95 per cent. The influence of technetium concentration of the pertechnetate solution on the labeling yield is evaluated and compensated by a slight adjustment of tin concentration when necessary. In vitro and in vivo stability studies show that 99Tcm-labelled red cells are suitable for determination of red cell volume, spleen and placental imaging, particularly in emergencies and in paediatrics."} {"id": "PMID:181113", "title": "Electrophysiological studies of normal and degenerating mouse neuromuscular junctions.", "content": "A quantitative study of the functional changes occurring at end-plates of phrenicotomised mouse hemidiaphragms was made. Analysis of the frequency of spontaneous transmitter release revealed large scale deviations from a Poisson based process commencing 6-7 h post-phrenicotomy. Short term bursts of miniature end-plate potentials (minEPPs) lasting 0.5-1.0 sec frequently occurred and also long term bursts of minEPPs which lasted from several minutes to 0.5 h or more. Following the long term bursts there was regularly a lasting silence at the end-plates. MinEPP amplitudes were analysed. Probability analyses suggest that the minEPPs are often normally distributed amongst two or more populations. This relationship was maintained during degeneration of the end-plate. No significant differences between the distribution of mean minEPP amplitudes of degenerating end-plates and normal end-plates were found. This suggests that no change in the quantal unit of transmitter release occurs during degeneration of the end-plate.", "contents": "Electrophysiological studies of normal and degenerating mouse neuromuscular junctions. A quantitative study of the functional changes occurring at end-plates of phrenicotomised mouse hemidiaphragms was made. Analysis of the frequency of spontaneous transmitter release revealed large scale deviations from a Poisson based process commencing 6-7 h post-phrenicotomy. Short term bursts of miniature end-plate potentials (minEPPs) lasting 0.5-1.0 sec frequently occurred and also long term bursts of minEPPs which lasted from several minutes to 0.5 h or more. Following the long term bursts there was regularly a lasting silence at the end-plates. MinEPP amplitudes were analysed. Probability analyses suggest that the minEPPs are often normally distributed amongst two or more populations. This relationship was maintained during degeneration of the end-plate. No significant differences between the distribution of mean minEPP amplitudes of degenerating end-plates and normal end-plates were found. This suggests that no change in the quantal unit of transmitter release occurs during degeneration of the end-plate."} {"id": "PMID:181114", "title": "NADH fluorescence, [K+]0 and oxygen consumption in cat cerebral cortex during direct cortical stimulation.", "content": "NADH fluorescence, sagittal sinus blood flow and sinus hemoglobin saturation were monitored simultaneously during direct cortical stimulation of a wide area of the anterior and mid suprasylvian and marginal gyri. The area monitored flurorometrically was located within the area apparently drained by the sinus, so that the flurometric changes could be correlated with oxygen consumption changes calculated from the sinus flow and saturation values. The onset and peak values of calculated oxygen consumption and NADH fluorescence changes usually occurred within several seconds of one another and high, significant (r greater than 0.9 and P less than 0.01) correlations were found between the maximum changes in both parameters following stimulation. The relation of cortical [K+]0 changes to oxygen consumption changes was also explored; again the magnitude of [K+]0 changes and calculated oxygen consumption changes correlated well. The demonstrated agreement between fluorometric and direct (sinus cannulation) measurements of oxidative metabolism reinforces the interpretation of in situ cortical fluorescence changes as indicative of changes in oxygen consumption rate", "contents": "NADH fluorescence, [K+]0 and oxygen consumption in cat cerebral cortex during direct cortical stimulation. NADH fluorescence, sagittal sinus blood flow and sinus hemoglobin saturation were monitored simultaneously during direct cortical stimulation of a wide area of the anterior and mid suprasylvian and marginal gyri. The area monitored flurorometrically was located within the area apparently drained by the sinus, so that the flurometric changes could be correlated with oxygen consumption changes calculated from the sinus flow and saturation values. The onset and peak values of calculated oxygen consumption and NADH fluorescence changes usually occurred within several seconds of one another and high, significant (r greater than 0.9 and P less than 0.01) correlations were found between the maximum changes in both parameters following stimulation. The relation of cortical [K+]0 changes to oxygen consumption changes was also explored; again the magnitude of [K+]0 changes and calculated oxygen consumption changes correlated well. The demonstrated agreement between fluorometric and direct (sinus cannulation) measurements of oxidative metabolism reinforces the interpretation of in situ cortical fluorescence changes as indicative of changes in oxygen consumption rate"} {"id": "PMID:181116", "title": "Effects of kainic acid, a cyclic analogue of glutamic acid, on cyclic nucleotide accumulation in slices of rat cerebellum.", "content": "The concentration of cyclic AMP (cAMP) and cyclic GMP (cGMP) in slices of rat cerebellum was increased markedly in the presence of 100 muM kainic acid, a cyclic analogue of glutamic acid. No acitvity was detected in other brain areas at various dosed or incubation times. Ksainic acid was significantly more potent than glutamic acid and other glutamate-like compounds. The increases in cAMP and cGMP could be differentially inhibited with theophylline or cocaine respectively, but both systems required calcium. Compounds similar in structure to kainic acid or glutamate did not block the effects of kainic acid.", "contents": "Effects of kainic acid, a cyclic analogue of glutamic acid, on cyclic nucleotide accumulation in slices of rat cerebellum. The concentration of cyclic AMP (cAMP) and cyclic GMP (cGMP) in slices of rat cerebellum was increased markedly in the presence of 100 muM kainic acid, a cyclic analogue of glutamic acid. No acitvity was detected in other brain areas at various dosed or incubation times. Ksainic acid was significantly more potent than glutamic acid and other glutamate-like compounds. The increases in cAMP and cGMP could be differentially inhibited with theophylline or cocaine respectively, but both systems required calcium. Compounds similar in structure to kainic acid or glutamate did not block the effects of kainic acid."} {"id": "PMID:181117", "title": "Regulation of neuronal properties by afferent connections. I. Functional changes in snail neurons following section of presysnaptic nerve fibers.", "content": "The left cerebral connective of snail ganglia containing afferent inputs to a particular neuron was sectioned. One week after the operation synaptic potentials were not obtained when the connective was stimulated, and they had not reappeared after 60 days. The current-voltage relationship of denervated cells showed a rectification in the hyperpolarizing direction, whereas that of control cells had an ohmic behavior. Depolarization or conductance changes produced by ACh or carbachol showed a supersensitivity in denervated cells, evidenced by a shift to the left of the dose-response curve and an increase of the maximal responses obtained. The reversal potential of ACh shifted from--22 mV in the control to--8 mV in denervated cells. Depolarization produced by serotonin was similar in control and denervated cells.", "contents": "Regulation of neuronal properties by afferent connections. I. Functional changes in snail neurons following section of presysnaptic nerve fibers. The left cerebral connective of snail ganglia containing afferent inputs to a particular neuron was sectioned. One week after the operation synaptic potentials were not obtained when the connective was stimulated, and they had not reappeared after 60 days. The current-voltage relationship of denervated cells showed a rectification in the hyperpolarizing direction, whereas that of control cells had an ohmic behavior. Depolarization or conductance changes produced by ACh or carbachol showed a supersensitivity in denervated cells, evidenced by a shift to the left of the dose-response curve and an increase of the maximal responses obtained. The reversal potential of ACh shifted from--22 mV in the control to--8 mV in denervated cells. Depolarization produced by serotonin was similar in control and denervated cells."} {"id": "PMID:181119", "title": "[Paget's disease of the breast in a male].", "content": "The case of a 78-year-old man with Paget's disease of the breast, described herein, appears to be only the 22nd histologically proven case of this rare condition; in over 100 years less than 50 cases have been reported. Since this patient had no underlying tumour or nodal involvement the operation consisted of total mastectomy with removal of axillary nodes only, rather than the classical radical mastectomy. All eczematoid lesions of the areola of the breast that persist for more than 2 weeks or are unilateral should be considered Paget's disease until proven otherwise by biopsy.", "contents": "[Paget's disease of the breast in a male]. The case of a 78-year-old man with Paget's disease of the breast, described herein, appears to be only the 22nd histologically proven case of this rare condition; in over 100 years less than 50 cases have been reported. Since this patient had no underlying tumour or nodal involvement the operation consisted of total mastectomy with removal of axillary nodes only, rather than the classical radical mastectomy. All eczematoid lesions of the areola of the breast that persist for more than 2 weeks or are unilateral should be considered Paget's disease until proven otherwise by biopsy."} {"id": "PMID:181121", "title": "Oat cell carcinoma of the lung. Early treatment results of combination radiation therapy and chemotherapy.", "content": "Since August 1974, 50 patients with histologically proven oat cell carcinoma of the lung were treated at Indiana University Hospitals with a combination of adriamycin, cyclophosphamide, Oncovin, BCG immunotherapy, and radiation therapy to the primary lung tumor and whole brain. Twenty-nine patients are eligible for a 6-month follow-up and are included in this report. All 29 patients responded to therapy; 12 patients (41%) had a minimum of 50% reduction in tumor mass and 17 patients (59%) had complete clinical remission of disease. Eight (38%) of the 29 patients have remained in complete remission from 6 to 14 months, and 90% of the patients survived a minimum of 6 months. This represents a considerable improvement in survival rates over what had been obtained at Indiana University Hospitals previously.", "contents": "Oat cell carcinoma of the lung. Early treatment results of combination radiation therapy and chemotherapy. Since August 1974, 50 patients with histologically proven oat cell carcinoma of the lung were treated at Indiana University Hospitals with a combination of adriamycin, cyclophosphamide, Oncovin, BCG immunotherapy, and radiation therapy to the primary lung tumor and whole brain. Twenty-nine patients are eligible for a 6-month follow-up and are included in this report. All 29 patients responded to therapy; 12 patients (41%) had a minimum of 50% reduction in tumor mass and 17 patients (59%) had complete clinical remission of disease. Eight (38%) of the 29 patients have remained in complete remission from 6 to 14 months, and 90% of the patients survived a minimum of 6 months. This represents a considerable improvement in survival rates over what had been obtained at Indiana University Hospitals previously."} {"id": "PMID:181122", "title": "Postoperative radiation therapy for residual Wilm's tumor. Review of Group III patients in the National Wilm's Tumor Study.", "content": "Fifty-eight patients with residual abdominal disease (Group III) are reviewed from National Wilm's Tumor Study \"1. The totap III) are reviewed from National Wilm's Tumor Study No. 1. The total number of abdominal recurrences is relatively low (eight cases). Local irradiation of the renal fossa would seem to be sufficient treatment for disease believed to be limited to that region, including cases of local spillage. Whole abdominal irradiation is recommended for gross, diffuse peritoneal contamination.", "contents": "Postoperative radiation therapy for residual Wilm's tumor. Review of Group III patients in the National Wilm's Tumor Study. Fifty-eight patients with residual abdominal disease (Group III) are reviewed from National Wilm's Tumor Study \"1. The totap III) are reviewed from National Wilm's Tumor Study No. 1. The total number of abdominal recurrences is relatively low (eight cases). Local irradiation of the renal fossa would seem to be sufficient treatment for disease believed to be limited to that region, including cases of local spillage. Whole abdominal irradiation is recommended for gross, diffuse peritoneal contamination."} {"id": "PMID:181123", "title": "Pulmonary function in survivors of Wilm's tumor. Patterns of impairment.", "content": "Whole-lung irradiation in Wilms' Tumor patients has been given prophylactically and for treatment of metastasis. Thirty-three children with Wilm's tumor who have survived for 4 to 20 years from the time of diagnosis were avaiable for study. Whole-lung irradiation was given in doses from 1163 to 1370 rads (orthovoltage). Eighteen patients (Group N) received no irradiation to the lungs. The remaining 15 patients were divided according to whether pulmonary irradiation was given for metastatic disease (Group M--10 patients) or for prophylactic treatment (Group P--five patients). All but five patients in Group N received at least one course of actinomycin D. A routine set of pulmonary function tests was done to assess possible abnormalities of lung volume and the mechanics of breathing. Group N was normal. The findings in Group M suggested moderately reduced lung volumes and may have also reflected obstruction of the large airways and/or a limited expiratory effort. Group P had essentially normal lung volumes but also appeared to have obstruction of the larger airways. Abnormalities were generally not severe; only two patients, in Group M, were symptomatic. Excess irradiation, presence of metastatsis, additional lung irradiation, and pneumonitis may have contributed to morbidity.", "contents": "Pulmonary function in survivors of Wilm's tumor. Patterns of impairment. Whole-lung irradiation in Wilms' Tumor patients has been given prophylactically and for treatment of metastasis. Thirty-three children with Wilm's tumor who have survived for 4 to 20 years from the time of diagnosis were avaiable for study. Whole-lung irradiation was given in doses from 1163 to 1370 rads (orthovoltage). Eighteen patients (Group N) received no irradiation to the lungs. The remaining 15 patients were divided according to whether pulmonary irradiation was given for metastatic disease (Group M--10 patients) or for prophylactic treatment (Group P--five patients). All but five patients in Group N received at least one course of actinomycin D. A routine set of pulmonary function tests was done to assess possible abnormalities of lung volume and the mechanics of breathing. Group N was normal. The findings in Group M suggested moderately reduced lung volumes and may have also reflected obstruction of the large airways and/or a limited expiratory effort. Group P had essentially normal lung volumes but also appeared to have obstruction of the larger airways. Abnormalities were generally not severe; only two patients, in Group M, were symptomatic. Excess irradiation, presence of metastatsis, additional lung irradiation, and pneumonitis may have contributed to morbidity."} {"id": "PMID:181124", "title": "Immune evaluation of lung cancer patients undergoing radiation therapy.", "content": "Immunocompetence, as determined by skin reactivity to five microbial antigens, dinitrochlorobenzene (DNCB), and percent and absolute number of total T and B rosette-forming cells (RFC), was assessed before and up to 180 days after radiotherapy in 29 patients with carcinoma of the lung. Pretherapy evaluation showed a depressed response to microbial antigens (only 38% positive), to DNCB (50% positive), and lower level of T-RFC. Postradiotherapy determinations were further depressed. Patients with positive pretherapy responses to microbial antigens and DNCB and higher than median absolute numbers at total T-RFC had significantly longer survival. These data suggest that pretherapy immune evaluation is a good prognostic indicator. No prognostic significance was found in B-RFC evaluation. No correlation was seen between the stage of disease (locally advanced or with distant metastases) and the pretherapy immune response.", "contents": "Immune evaluation of lung cancer patients undergoing radiation therapy. Immunocompetence, as determined by skin reactivity to five microbial antigens, dinitrochlorobenzene (DNCB), and percent and absolute number of total T and B rosette-forming cells (RFC), was assessed before and up to 180 days after radiotherapy in 29 patients with carcinoma of the lung. Pretherapy evaluation showed a depressed response to microbial antigens (only 38% positive), to DNCB (50% positive), and lower level of T-RFC. Postradiotherapy determinations were further depressed. Patients with positive pretherapy responses to microbial antigens and DNCB and higher than median absolute numbers at total T-RFC had significantly longer survival. These data suggest that pretherapy immune evaluation is a good prognostic indicator. No prognostic significance was found in B-RFC evaluation. No correlation was seen between the stage of disease (locally advanced or with distant metastases) and the pretherapy immune response."} {"id": "PMID:181125", "title": "Urinary cholesterol. VIII. Its excretion in women with ovarian neoplasms.", "content": "The urinary excretion of nonesterified cholesterol (NEC) has been investigated in 57 women with ovarian neoplasms and/or related nonneoplastic diseases. Twelve patients had benign tumors or lesions and 45 had malignant neoplasms of their ovaries. All patients with nonmalignant ovarian tumors or lesions had normal NEC excretion irrespective of the type of tumor or lesion or its degree of extension. In contrast, urinary NEC hyperexcretion occurred with the following frequencies in patients with active malignant ovarian neoplasms: 18 of 19 cystadenocarcinomas of the serous and/or mucinous types; one of one endometrioid carcinoma; four of four malignant granulosa cell tumors; two of two mixed malignant germ cell tumors; and one of one malignant mixed m\u00fcllerian tumor. Single cases of clear cell carcinoma and of rhabdomyosarcoma had a normal NEC excretion. Urinary hyperexcretion of NEC was also found after surgery in two of seven surviving patients with apparently localized resectable disease according to their staging. It is possible that in these two patients NEC hyperexcretion was due to undetected foci of cancer (wrong staging), since neither omental and peritoneal biopsies, nor cytologic examination of peritoneal washings or free fluid were performed. A normal excretion of urinary NEC has been characteristic of 19 of 21 surviving patients treated by surgery and adjunctive therapy in whom we have performed follow-up NEC determinations. They were 16 of 18 cystadenocarcinomas malignant germ cell tumor. The 94% correlation between the presence of proven active ovarian carcinomas and urinary NEC hyperexcretion is significant. The clinical significance of this investigation is even greater when one considers that cystadenocarcinomas constitute more than 75% of all primary malignant ovarian tumors.", "contents": "Urinary cholesterol. VIII. Its excretion in women with ovarian neoplasms. The urinary excretion of nonesterified cholesterol (NEC) has been investigated in 57 women with ovarian neoplasms and/or related nonneoplastic diseases. Twelve patients had benign tumors or lesions and 45 had malignant neoplasms of their ovaries. All patients with nonmalignant ovarian tumors or lesions had normal NEC excretion irrespective of the type of tumor or lesion or its degree of extension. In contrast, urinary NEC hyperexcretion occurred with the following frequencies in patients with active malignant ovarian neoplasms: 18 of 19 cystadenocarcinomas of the serous and/or mucinous types; one of one endometrioid carcinoma; four of four malignant granulosa cell tumors; two of two mixed malignant germ cell tumors; and one of one malignant mixed m\u00fcllerian tumor. Single cases of clear cell carcinoma and of rhabdomyosarcoma had a normal NEC excretion. Urinary hyperexcretion of NEC was also found after surgery in two of seven surviving patients with apparently localized resectable disease according to their staging. It is possible that in these two patients NEC hyperexcretion was due to undetected foci of cancer (wrong staging), since neither omental and peritoneal biopsies, nor cytologic examination of peritoneal washings or free fluid were performed. A normal excretion of urinary NEC has been characteristic of 19 of 21 surviving patients treated by surgery and adjunctive therapy in whom we have performed follow-up NEC determinations. They were 16 of 18 cystadenocarcinomas malignant germ cell tumor. The 94% correlation between the presence of proven active ovarian carcinomas and urinary NEC hyperexcretion is significant. The clinical significance of this investigation is even greater when one considers that cystadenocarcinomas constitute more than 75% of all primary malignant ovarian tumors."} {"id": "PMID:181126", "title": "Radiation-induced intracranial malignant fibrous histiocytoma.", "content": "An autopsy case of radiation-induced intracranial malignant fibrous histiocytoma (fibroxanthosarcoma) is reported. The tumor developed in the region of the sella turcica 11 years after high dose radiotherapy of a chromophobe adenoma of the pituitary. The tumor had infiltrated the base of the brain as well as the base of the skull. Metastases were not found. The tumor was composed of an admixture of bizarre fibroblasts, histiocytes and giant cells, xanthoma cells and siderophages, with a storiform fibrous stroma. This appears to be the first documented instance of a malignant fibrous histiocytoma occurring intracranially after local x-irradiation.", "contents": "Radiation-induced intracranial malignant fibrous histiocytoma. An autopsy case of radiation-induced intracranial malignant fibrous histiocytoma (fibroxanthosarcoma) is reported. The tumor developed in the region of the sella turcica 11 years after high dose radiotherapy of a chromophobe adenoma of the pituitary. The tumor had infiltrated the base of the brain as well as the base of the skull. Metastases were not found. The tumor was composed of an admixture of bizarre fibroblasts, histiocytes and giant cells, xanthoma cells and siderophages, with a storiform fibrous stroma. This appears to be the first documented instance of a malignant fibrous histiocytoma occurring intracranially after local x-irradiation."} {"id": "PMID:181127", "title": "Signet-ring stromal tumor of ovary. Histochemical, light, and electron microscopic study.", "content": "A peculiar primary ovarian neoplasm occurring in a 28-year-old woman is presented. The tumor cells showed extensive cytoplasmic vacuolation, resulting in a \"signet-ring\" appearance similar to what was described in Krukenberg tumors. The tumor was studied histochemically, as well as by light and electron microscopy. The cells appeared to be uniform. A moderately electron-dense flocculent material was present in the cytoplasmic vacuoles. similar material was seen in the intercellular matrix with some fibrillary structures suggesting a protein structure. This, coupled with the lack of any basement membrane material around the tumor cells, indicates a mesenchymal tumor that is probably derived from the multipotent ovarian stromal cell. The features that help to differentiate this tumor from other ovarian tumors with clear or vacuolated cells are discussed. Because of its gross and microscopic appearance, the tumor is expected to behave in a benign fashion.", "contents": "Signet-ring stromal tumor of ovary. Histochemical, light, and electron microscopic study. A peculiar primary ovarian neoplasm occurring in a 28-year-old woman is presented. The tumor cells showed extensive cytoplasmic vacuolation, resulting in a \"signet-ring\" appearance similar to what was described in Krukenberg tumors. The tumor was studied histochemically, as well as by light and electron microscopy. The cells appeared to be uniform. A moderately electron-dense flocculent material was present in the cytoplasmic vacuoles. similar material was seen in the intercellular matrix with some fibrillary structures suggesting a protein structure. This, coupled with the lack of any basement membrane material around the tumor cells, indicates a mesenchymal tumor that is probably derived from the multipotent ovarian stromal cell. The features that help to differentiate this tumor from other ovarian tumors with clear or vacuolated cells are discussed. Because of its gross and microscopic appearance, the tumor is expected to behave in a benign fashion."} {"id": "PMID:181128", "title": "Gastrinoma of duodenal G-cell origin.", "content": "A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal \"carcinoid-islet cell tumor.\" Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. \"Carcinoidislet cell tumors,\" like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques.", "contents": "Gastrinoma of duodenal G-cell origin. A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal \"carcinoid-islet cell tumor.\" Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. \"Carcinoidislet cell tumors,\" like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques."} {"id": "PMID:181129", "title": "Simultaneous occurrence of melanotic neuroectodermal tumor and brain heterotopia in the oropharynx.", "content": "A case is described of heterotopic brain tissue with simultaneous occurrence of melanotic neuroectodermal tumor in the oropharynx of a 6-week-old infant. The melanotic neuroectodermal tumor was embedded within the heterotopic glial tissue. This coexistence leads us to speculate that a defect causing a pinching-off of both neural crest cap and medullary epithelium of neural tube might have taken place at, or before, the 25-30 somite stage. The displaced embryonic structures subsequently differentiated into glial tissue, choroid plexus, and melanotic neuroectodermal tumor. This observation may be interpreted as further support in favor of a neural crest origin of juvenile melanotic neuroectodermal tumor.", "contents": "Simultaneous occurrence of melanotic neuroectodermal tumor and brain heterotopia in the oropharynx. A case is described of heterotopic brain tissue with simultaneous occurrence of melanotic neuroectodermal tumor in the oropharynx of a 6-week-old infant. The melanotic neuroectodermal tumor was embedded within the heterotopic glial tissue. This coexistence leads us to speculate that a defect causing a pinching-off of both neural crest cap and medullary epithelium of neural tube might have taken place at, or before, the 25-30 somite stage. The displaced embryonic structures subsequently differentiated into glial tissue, choroid plexus, and melanotic neuroectodermal tumor. This observation may be interpreted as further support in favor of a neural crest origin of juvenile melanotic neuroectodermal tumor."} {"id": "PMID:181130", "title": "Familial glioblastoma with hepatic focal nodular hyperplasia.", "content": "Two siblings succumbed to glioblastoma multiforme, associated with hepatic focal nodular hyperplasia and cafe-au-lait spots. One sibling had syndactyly and multiple colonic polyps, while the other had an angiomatous malformation in the brain. Their mother died of myasthenia gravis. The findings suggest a hamartomatous syndrome of malformations that predisposes to brain tumors.", "contents": "Familial glioblastoma with hepatic focal nodular hyperplasia. Two siblings succumbed to glioblastoma multiforme, associated with hepatic focal nodular hyperplasia and cafe-au-lait spots. One sibling had syndactyly and multiple colonic polyps, while the other had an angiomatous malformation in the brain. Their mother died of myasthenia gravis. The findings suggest a hamartomatous syndrome of malformations that predisposes to brain tumors."} {"id": "PMID:181131", "title": "Vesicocolic fistula due to \"collision\" between adenocarcinoma of the colon and transitional cell carcinoma of the urinary bladder.", "content": "A patient with sigmoidocystic fistula due to \"collision\" between mucoid adenocarcinoma of the colon and transitional cell carcinoma of the urinary bladder is presented. A wide resection of the colonic tumor, along with the involved bladder segment, and a decompressive colostomy with bladder drainage by catheter, were performed. The clinical symptoms, diagnostic procedures, operative treatment, and prognosis are discussed. Although fistular formation is an indication of advanced carcinoma, wide resection of the tumor and the associated fistular along with the node-bearing area will result in a reasonable percentage of 5-year survivals.", "contents": "Vesicocolic fistula due to \"collision\" between adenocarcinoma of the colon and transitional cell carcinoma of the urinary bladder. A patient with sigmoidocystic fistula due to \"collision\" between mucoid adenocarcinoma of the colon and transitional cell carcinoma of the urinary bladder is presented. A wide resection of the colonic tumor, along with the involved bladder segment, and a decompressive colostomy with bladder drainage by catheter, were performed. The clinical symptoms, diagnostic procedures, operative treatment, and prognosis are discussed. Although fistular formation is an indication of advanced carcinoma, wide resection of the tumor and the associated fistular along with the node-bearing area will result in a reasonable percentage of 5-year survivals."} {"id": "PMID:181132", "title": "Chemotherapy of invasive thymoma.", "content": "Despite conventional therapy, including surgery and radiation, 5-year survival for invasive thymoma remains poor. Chemotherapeutic agents, including cisdiamminedichloroplatinum, prednisone, adriamycin and nitrogen mustard-vincristine-vinblastine-procarbazine, and bleomycin-adriamycin-CCNU-vincristine have produced short-term remissions. In view of the small number of cases seen in any one institution, a cooperative study to evaluate chemotherapeutic efficacy in malignant thymoma would seem worthwhile.", "contents": "Chemotherapy of invasive thymoma. Despite conventional therapy, including surgery and radiation, 5-year survival for invasive thymoma remains poor. Chemotherapeutic agents, including cisdiamminedichloroplatinum, prednisone, adriamycin and nitrogen mustard-vincristine-vinblastine-procarbazine, and bleomycin-adriamycin-CCNU-vincristine have produced short-term remissions. In view of the small number of cases seen in any one institution, a cooperative study to evaluate chemotherapeutic efficacy in malignant thymoma would seem worthwhile."} {"id": "PMID:181133", "title": "Synovial sarcoma with brain metastases. Report of a case responding to supervoltage irradiation and review of the literature.", "content": "A 32-year-old man with clinically evident brain metastases from synovial sarcoma had a complete clinical remission after cerebral radiation. At autopsy, residual tumor was found in the brain.", "contents": "Synovial sarcoma with brain metastases. Report of a case responding to supervoltage irradiation and review of the literature. A 32-year-old man with clinically evident brain metastases from synovial sarcoma had a complete clinical remission after cerebral radiation. At autopsy, residual tumor was found in the brain."} {"id": "PMID:181134", "title": "Hypothalamus and cytodifferentiation of the foetal pituitary gland. Study in vivo.", "content": "To investigate whether the hypothalamus is involved in the cytodifferentiation of the anterior pituitary gland, rat foetuses were encephalectomized in utero on day 16 of pregnancy. Pituitary sections from encephalectomized and normal littermate foetuses were studied on day 21 with the immunofluorescence technique using antibodies anti alpha-MSH, anti beta-MSH, anti alpha-(17-39) ACTH and anti beta-(1-24) ACTH. On day 16, only the anti beta-MSH revealed a few cells in the pars distalis but not in the pars intermedia. On the other hand, on day 21, the pituitary cells reacting with antibodies anti alpha-MSH, anti beta-MSH and anti alpha-(17-39) ACTH were as numerous in the encephalectomized foetuses as in the normal littermate foetuses. The cells revealed with the antibody anti beta-(1-24) ACTH were less numerous and less fluorescent in the pars distalis and intermedia of the hypophysis of the encephalectomized foetuses. On day 21, the adrenals of the encephalectomized foetuses were atrophied in comparison with those of the normal littermate foetuses but they were larger than on day 16. These data suggest that the cytodifferentiation of the corticotroph and melanotroph cells of the hypophysis occurs without the influence of the hypothalamus which is necessary for the normal release of ACTH.", "contents": "Hypothalamus and cytodifferentiation of the foetal pituitary gland. Study in vivo. To investigate whether the hypothalamus is involved in the cytodifferentiation of the anterior pituitary gland, rat foetuses were encephalectomized in utero on day 16 of pregnancy. Pituitary sections from encephalectomized and normal littermate foetuses were studied on day 21 with the immunofluorescence technique using antibodies anti alpha-MSH, anti beta-MSH, anti alpha-(17-39) ACTH and anti beta-(1-24) ACTH. On day 16, only the anti beta-MSH revealed a few cells in the pars distalis but not in the pars intermedia. On the other hand, on day 21, the pituitary cells reacting with antibodies anti alpha-MSH, anti beta-MSH and anti alpha-(17-39) ACTH were as numerous in the encephalectomized foetuses as in the normal littermate foetuses. The cells revealed with the antibody anti beta-(1-24) ACTH were less numerous and less fluorescent in the pars distalis and intermedia of the hypophysis of the encephalectomized foetuses. On day 21, the adrenals of the encephalectomized foetuses were atrophied in comparison with those of the normal littermate foetuses but they were larger than on day 16. These data suggest that the cytodifferentiation of the corticotroph and melanotroph cells of the hypophysis occurs without the influence of the hypothalamus which is necessary for the normal release of ACTH."} {"id": "PMID:181135", "title": "Fine structure of taste buds in the barbel of the catfish, Ictalurus punctatus.", "content": "Taste buds occur in the epithelium of the catfish barbel along its entire length. Two major cell types, light and dark cells, occupy the upper two-thirds of the taste bud. A third cell type, the basal cell, lies on the basal lamina and is essentially separated from the light and dark cells by a plexus of unmyelinated nerve fibers. The dark cells have branching processes, both apically and basally whereas the light cells have a single apical process and many basal processes. The apical processes of dark cells contain secretory granules, while the apical processes of light cells contain an abundant agranular endoplasmic reticulum. Light cell nuclei contain bundles of 10 nm filaments, often arranged in the shape of a cup or ring, but nucleoli are rarely seen. It is suggested that this morphology indicates a low degree of RNA synthesis by light cells. The basal cells contain large numbers of vesicles, about 60 nm in diameter, which are sometimes seen in clumps in relation to an adjacent nerve fiber in a configuration resembling a synapse. Curiously, although basal cells present a large surface to the basal lamina, there are no hemidesmosomes. This suggests that the basal cell does not originate from the epidermis.", "contents": "Fine structure of taste buds in the barbel of the catfish, Ictalurus punctatus. Taste buds occur in the epithelium of the catfish barbel along its entire length. Two major cell types, light and dark cells, occupy the upper two-thirds of the taste bud. A third cell type, the basal cell, lies on the basal lamina and is essentially separated from the light and dark cells by a plexus of unmyelinated nerve fibers. The dark cells have branching processes, both apically and basally whereas the light cells have a single apical process and many basal processes. The apical processes of dark cells contain secretory granules, while the apical processes of light cells contain an abundant agranular endoplasmic reticulum. Light cell nuclei contain bundles of 10 nm filaments, often arranged in the shape of a cup or ring, but nucleoli are rarely seen. It is suggested that this morphology indicates a low degree of RNA synthesis by light cells. The basal cells contain large numbers of vesicles, about 60 nm in diameter, which are sometimes seen in clumps in relation to an adjacent nerve fiber in a configuration resembling a synapse. Curiously, although basal cells present a large surface to the basal lamina, there are no hemidesmosomes. This suggests that the basal cell does not originate from the epidermis."} {"id": "PMID:181138", "title": "Specific binding of the type C viral core protein p12 with purified viral RNA.", "content": "The major viral phosphoproteins (p12) of the Rauscher murine leukemia virus (R-MuLV) and the simian sarcoma-associated virus (SSAV) bind in vitro to their homologous 70S and 35S viral RNAs. Using purified 32P-labeled RNA and 125I-labeled p12 protein, complexes that are stabilized by formaldehyde-cross-linking can be readily detected after velocity gradient centrifugation. The in vitro reconstructed ribonucleoprotein complexes are seen only with p12 proteins incubated with viral RNAs isolated from the same type C viruses; no such complexes form with heterologous protein-RNA mixtures. Homologous but not heterologous p12 molecules compete with radiolabeled p12 protein for the specific viral RNA binding sites. The competition assay permits the detection of 10 ng of viral p12 protein. The major internal protein of type C viruses (p30) does not bind to viral RNA using identical assay conditions. From the specific activities of the radiolabeled components and also by equilibrium sedimentation analysis, we estimate that fewer than 15 molecules of p12 protein bind to each molecule of viral RNA. Both the specificity and stoichiometry of the p12-RNA interactions suggest that these RNA tumor virus proteins have a regulatory role in cells.", "contents": "Specific binding of the type C viral core protein p12 with purified viral RNA. The major viral phosphoproteins (p12) of the Rauscher murine leukemia virus (R-MuLV) and the simian sarcoma-associated virus (SSAV) bind in vitro to their homologous 70S and 35S viral RNAs. Using purified 32P-labeled RNA and 125I-labeled p12 protein, complexes that are stabilized by formaldehyde-cross-linking can be readily detected after velocity gradient centrifugation. The in vitro reconstructed ribonucleoprotein complexes are seen only with p12 proteins incubated with viral RNAs isolated from the same type C viruses; no such complexes form with heterologous protein-RNA mixtures. Homologous but not heterologous p12 molecules compete with radiolabeled p12 protein for the specific viral RNA binding sites. The competition assay permits the detection of 10 ng of viral p12 protein. The major internal protein of type C viruses (p30) does not bind to viral RNA using identical assay conditions. From the specific activities of the radiolabeled components and also by equilibrium sedimentation analysis, we estimate that fewer than 15 molecules of p12 protein bind to each molecule of viral RNA. Both the specificity and stoichiometry of the p12-RNA interactions suggest that these RNA tumor virus proteins have a regulatory role in cells."} {"id": "PMID:181139", "title": "Accumulation of cystine auxotrophic thymocytes accompanying type C viral leukemogenesis in the mouse.", "content": "Certain continuous lymphoid and myeloid tumor cell lines of rodent origin are unable to grow in tissue culture in the absence of pre-formed L-cystine (CYS). In contrast, three NZB murine lymphoid cell lines obtained from NZB mice free of hematopoietic neoplasm can grow as well in cystine-deficient media containing L-cystathionine (CSN), the immediate precursor of CYS in the biosynthetic pathway, as in cystine sufficient medium. The former class of cells is, therefore, CYS auxotrophs (CYS-) and the latter CYS prototrophs (CYS+). Compared to CYS+ cells, the CYS- lines appear to be relatively deficient in the enzyme cystathionase, which catalyzes the cleavage of CSN to CYS and alpha-ketobutyrate. Using protein synthetic capacity as a criterion, normal thymocytes from mixed-bred Swiss mice behave like CYS prototrophs, while those from littermates bearing Moloney type C virus-induced thymic tumors behave like CYS auxotrophs. The former are also characterized by substantially higher levels of cystathionase than the latter. Extracts of thymocytes from tumor-free AKR mouse thymus are also characterized by higher levels of cystathionase activity than extracts of spontaneous AKR thymomas. Exogenous in vitro type C virus infection of a CYS+ cell results in vigorous virus production but no concomitant reduction in cystathionase activity. Thus viral replication alone in any random lymphoid cell is not sufficient to alter the enzyme level. The data therefore suggests that CYS auxotrophy may closely accompany neoplastic transformation of certain hematopoietic cells in vivo, including that induced by certain \"thymic\" type C viruses.", "contents": "Accumulation of cystine auxotrophic thymocytes accompanying type C viral leukemogenesis in the mouse. Certain continuous lymphoid and myeloid tumor cell lines of rodent origin are unable to grow in tissue culture in the absence of pre-formed L-cystine (CYS). In contrast, three NZB murine lymphoid cell lines obtained from NZB mice free of hematopoietic neoplasm can grow as well in cystine-deficient media containing L-cystathionine (CSN), the immediate precursor of CYS in the biosynthetic pathway, as in cystine sufficient medium. The former class of cells is, therefore, CYS auxotrophs (CYS-) and the latter CYS prototrophs (CYS+). Compared to CYS+ cells, the CYS- lines appear to be relatively deficient in the enzyme cystathionase, which catalyzes the cleavage of CSN to CYS and alpha-ketobutyrate. Using protein synthetic capacity as a criterion, normal thymocytes from mixed-bred Swiss mice behave like CYS prototrophs, while those from littermates bearing Moloney type C virus-induced thymic tumors behave like CYS auxotrophs. The former are also characterized by substantially higher levels of cystathionase than the latter. Extracts of thymocytes from tumor-free AKR mouse thymus are also characterized by higher levels of cystathionase activity than extracts of spontaneous AKR thymomas. Exogenous in vitro type C virus infection of a CYS+ cell results in vigorous virus production but no concomitant reduction in cystathionase activity. Thus viral replication alone in any random lymphoid cell is not sufficient to alter the enzyme level. The data therefore suggests that CYS auxotrophy may closely accompany neoplastic transformation of certain hematopoietic cells in vivo, including that induced by certain \"thymic\" type C viruses."} {"id": "PMID:181140", "title": "Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans.", "content": "The sulfated glycosaminoglycan, heparin, was found to release 125I-labeled low density lipoprotein (125I-LDL) from its receptor site on the surface of normal human fibroblasts. Measurement of the amount of 125I-LDL released by heparin permitted the resolution of the total cellular uptake of 125I-LDL at 37 degrees C into two components: first, an initial rapid, high affinity binding of the lipoprotein to the surface receptor, from which the 125I-LDL could be released by heparin, and second, a slower process attributable to an endocytosis of the receptor-bound lipoprotein, which rendered it resistant to heparin release. At 4 degrees C the amount of heparin-releasable 125I-LDL was similar to that at 37 degrees C, but interiorization of the lipoprotein did not occur at the lower temperature. The physiologic importance of the cell surface LDL receptor was emphasized by the finding that mutant fibroblasts from a subject with homozygous Familial Hypercholesterolemia, which lack the ability to take up 125I-LDL at 37 degrees C, did not show cell surface binding of 125I-LDL, as measured by heparin release, at either 4 degrees C or 37 degrees C. Although heparin released 125I-LDL from its binding site, it did not release 3H-concanavalin A from its surface receptor, and conversely, alpha-methyl-D-mannopyranoside, which released 3H-concanavalin A, did not release surface-bound 125I-LDL. When added to the culture medium simultaneously with LDL, heparin prevented the binding of LDL to its receptor and hence prevented the LDL-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. The uptake of LDL by fibroblasts is proposed as a model of receptor-mediated adsorptive endocytosis of macromolecules in human cells.", "contents": "Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. The sulfated glycosaminoglycan, heparin, was found to release 125I-labeled low density lipoprotein (125I-LDL) from its receptor site on the surface of normal human fibroblasts. Measurement of the amount of 125I-LDL released by heparin permitted the resolution of the total cellular uptake of 125I-LDL at 37 degrees C into two components: first, an initial rapid, high affinity binding of the lipoprotein to the surface receptor, from which the 125I-LDL could be released by heparin, and second, a slower process attributable to an endocytosis of the receptor-bound lipoprotein, which rendered it resistant to heparin release. At 4 degrees C the amount of heparin-releasable 125I-LDL was similar to that at 37 degrees C, but interiorization of the lipoprotein did not occur at the lower temperature. The physiologic importance of the cell surface LDL receptor was emphasized by the finding that mutant fibroblasts from a subject with homozygous Familial Hypercholesterolemia, which lack the ability to take up 125I-LDL at 37 degrees C, did not show cell surface binding of 125I-LDL, as measured by heparin release, at either 4 degrees C or 37 degrees C. Although heparin released 125I-LDL from its binding site, it did not release 3H-concanavalin A from its surface receptor, and conversely, alpha-methyl-D-mannopyranoside, which released 3H-concanavalin A, did not release surface-bound 125I-LDL. When added to the culture medium simultaneously with LDL, heparin prevented the binding of LDL to its receptor and hence prevented the LDL-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. The uptake of LDL by fibroblasts is proposed as a model of receptor-mediated adsorptive endocytosis of macromolecules in human cells."} {"id": "PMID:181142", "title": "Propagation of a segment of bacteriophage lamda-DNA in monkey cells after covalent linkage to a defective simian virus 40 genome.", "content": "A 520 base pair DNA segment was excised from the bacteriophage lamda-genome by cleavage with the bacterial restriction endonuclease, endo R. Hindll. This segment was covalently joined in vitro to an 880 base pair simian virus 40 (SV40) DNA segment which contains the initation site for SV40 DNA replication. The latter segment was derived from the genome of a defective reiteration mutant of SV40 also by endo R. Hindlll cleavage. When the recombinant molecule, together with wild-type SV40 DNA as helper, was introduced into monkey cells by DNA infection, replication of the lamda-DNA sequences was observed, and hybrid genomes were encapsidated into progeny SV40 virions. The structure of the lamda-DNA segment after serial passage in monkey cells was examined by use of restriction endonucleases and electron microscopic heteroduplex analysis.", "contents": "Propagation of a segment of bacteriophage lamda-DNA in monkey cells after covalent linkage to a defective simian virus 40 genome. A 520 base pair DNA segment was excised from the bacteriophage lamda-genome by cleavage with the bacterial restriction endonuclease, endo R. Hindll. This segment was covalently joined in vitro to an 880 base pair simian virus 40 (SV40) DNA segment which contains the initation site for SV40 DNA replication. The latter segment was derived from the genome of a defective reiteration mutant of SV40 also by endo R. Hindlll cleavage. When the recombinant molecule, together with wild-type SV40 DNA as helper, was introduced into monkey cells by DNA infection, replication of the lamda-DNA sequences was observed, and hybrid genomes were encapsidated into progeny SV40 virions. The structure of the lamda-DNA segment after serial passage in monkey cells was examined by use of restriction endonucleases and electron microscopic heteroduplex analysis."} {"id": "PMID:181143", "title": "Topography of polyoma virus messenger RNA molecules.", "content": "The different species of polyoma virus-spedific RNA molecules present in the cytoplasm of 3T6 cells 30 hr after viral infection have been characterized by molecular hybridization between nonradioactive polyadenlated RNA, fractionated by sedimentation through sucrose-formamide density gradients, and the 32P-labeled separated strands of restriction endonuclease fragments of polyoma DNA. Two relatively abundant RNA molecules, sedimenting at 16S and at 19S, transcribed from the L strand of the viral DNA, as well as a minor 20S species transcribed from the E strand of the DNA, were detected. The most abundant viral transcript, the 16S RNA molecule, was estimated to be complementary to the 22% of the L-strand DNA extending from 47 to 25 map units. The less abundant 19S L DNA strand transcript included all the sequences present in the 16S RNA and mapped between 68 and 25 map units. The minor 20S RNA molecule was tentatively identified as a transcript of the E-strand DNA from the entire early region of the polyoma genome. These three viral RNA molecules together exhaust greater than 95% of the coding capacity of the viral DNA. A small region of the DNA (4-5%), including the origin of DNA replication, does not appear to determine sequences present among the major stable species of vital mRNA.", "contents": "Topography of polyoma virus messenger RNA molecules. The different species of polyoma virus-spedific RNA molecules present in the cytoplasm of 3T6 cells 30 hr after viral infection have been characterized by molecular hybridization between nonradioactive polyadenlated RNA, fractionated by sedimentation through sucrose-formamide density gradients, and the 32P-labeled separated strands of restriction endonuclease fragments of polyoma DNA. Two relatively abundant RNA molecules, sedimenting at 16S and at 19S, transcribed from the L strand of the viral DNA, as well as a minor 20S species transcribed from the E strand of the DNA, were detected. The most abundant viral transcript, the 16S RNA molecule, was estimated to be complementary to the 22% of the L-strand DNA extending from 47 to 25 map units. The less abundant 19S L DNA strand transcript included all the sequences present in the 16S RNA and mapped between 68 and 25 map units. The minor 20S RNA molecule was tentatively identified as a transcript of the E-strand DNA from the entire early region of the polyoma genome. These three viral RNA molecules together exhaust greater than 95% of the coding capacity of the viral DNA. A small region of the DNA (4-5%), including the origin of DNA replication, does not appear to determine sequences present among the major stable species of vital mRNA."} {"id": "PMID:181144", "title": "Phenotypic mixing between N- and B-tropic murine leukemia viruses: infectious particles with dual sensitivity to Fv-1 restriction.", "content": "In effort to understand how N or B tropism is determined in murine leukemia virus (MuLV) particles, we analyzed the MuLV produced after dual infection of mouse cells by N- and B-tropic MuLV. The progeny MuLV from such a mixed infection are sensitive to Fv-1 restriction in both N- and B-type cells, but are still highly infectious for mouse cells which do not exhibit Fv-1 restriction. This dual sensitivity to Fv-1 restriction is a phenotypic property of MuLV produced by mixedly infected cells, since individual virus clones derived from this MuLV are either N- or B-tropic. In further experiments, we superinfected murine sarcoma virus (MSV)-transformed cells with mixtures of N- and B-tropic MuLVs. The rescued MSV is restricted in its ability to transforms both N- and B-type cells. The results suggest that N- and B-tropic MuLVs specify different determinants, which are incorporated into virions along with the viral genome and which are the recognition sites for Fv-1 restriction. The presence of a given determinant in a virion renders the virus sensitive to restriction in cells of the opposite Fv-1 type.", "contents": "Phenotypic mixing between N- and B-tropic murine leukemia viruses: infectious particles with dual sensitivity to Fv-1 restriction. In effort to understand how N or B tropism is determined in murine leukemia virus (MuLV) particles, we analyzed the MuLV produced after dual infection of mouse cells by N- and B-tropic MuLV. The progeny MuLV from such a mixed infection are sensitive to Fv-1 restriction in both N- and B-type cells, but are still highly infectious for mouse cells which do not exhibit Fv-1 restriction. This dual sensitivity to Fv-1 restriction is a phenotypic property of MuLV produced by mixedly infected cells, since individual virus clones derived from this MuLV are either N- or B-tropic. In further experiments, we superinfected murine sarcoma virus (MSV)-transformed cells with mixtures of N- and B-tropic MuLVs. The rescued MSV is restricted in its ability to transforms both N- and B-type cells. The results suggest that N- and B-tropic MuLVs specify different determinants, which are incorporated into virions along with the viral genome and which are the recognition sites for Fv-1 restriction. The presence of a given determinant in a virion renders the virus sensitive to restriction in cells of the opposite Fv-1 type."} {"id": "PMID:181145", "title": "The construction of viable nuclear-cytoplasmic hybrid cells by nuclear transplantation.", "content": "Using the mouse L-cell line as a model system, a generalized approach is presented for nuclear transplantation in cultured cells resulting in the construction of cytoplasmic-nuclear hybrid cells. Techniques were developed for the preparation of cytoplast and karyoplasts having minimum contamination by parent whole cells. Sendai virusmediated fusion was performed in a manner which maximized the formation of the desired fusion products-cells having one cell equivalent of cytoplasm from one parent and a nucleus from a second parent. The viability of the fusion products was established by examination of photographic records of the developing cultures. Using these techniques, we found that nuclei could be introduced routinely into 10-30% of a cytoplast culture. From determinations of the increase in cell number with time, it was estimated that at least 30% of the reconstructed cells were capable of division. The approach was next applied to the formation of hybrid cells from L-cell cytoplasts and A9 cell karyoplasts. The A9 cell line is an azaguanine-resistant derivative of L cells. Thus any whole cells remaining in the culture of fused cells were readily eliminated by treatment with the purine analogue. The culture of remaining cytoplasmic-nuclear hybrid cells grew to confluence in the presence of azaguanine. The applicability of the approach to the construction of hybrid cells using parent lines from different organisms is briefly discussed.", "contents": "The construction of viable nuclear-cytoplasmic hybrid cells by nuclear transplantation. Using the mouse L-cell line as a model system, a generalized approach is presented for nuclear transplantation in cultured cells resulting in the construction of cytoplasmic-nuclear hybrid cells. Techniques were developed for the preparation of cytoplast and karyoplasts having minimum contamination by parent whole cells. Sendai virusmediated fusion was performed in a manner which maximized the formation of the desired fusion products-cells having one cell equivalent of cytoplasm from one parent and a nucleus from a second parent. The viability of the fusion products was established by examination of photographic records of the developing cultures. Using these techniques, we found that nuclei could be introduced routinely into 10-30% of a cytoplast culture. From determinations of the increase in cell number with time, it was estimated that at least 30% of the reconstructed cells were capable of division. The approach was next applied to the formation of hybrid cells from L-cell cytoplasts and A9 cell karyoplasts. The A9 cell line is an azaguanine-resistant derivative of L cells. Thus any whole cells remaining in the culture of fused cells were readily eliminated by treatment with the purine analogue. The culture of remaining cytoplasmic-nuclear hybrid cells grew to confluence in the presence of azaguanine. The applicability of the approach to the construction of hybrid cells using parent lines from different organisms is briefly discussed."} {"id": "PMID:181146", "title": "Quantitation of elongating form A and B RNA polymerases in chick oviduct nuclei and effects of estradiol.", "content": "The number of elongating form A and B RNA polymerases in chick oviduct nuclei was estimated by measuring incorportaion of 3H-UTP into 3' termini of nascent RNA chains in the presence of heparin to inhibit initiation, and quantitation labeled uridine released from these termini after alkaline hydrolysis. The method corrects for conversion of UMP to uridine (U) during manipulations and for production of 3' termini by ribonucleases and phosphatases. The results indicate that a large fraction of RNA polymerases elongating in vivo is retained in isolated nuclei: per diploid genome, approximately 1 x104 form B and 2 x103 form A enzymes are present. These levels are sufficient to maintain normal in vivo rates of mRNA and rRNA synthesis, but the average density of packing of polymerases on DNA is considerably less than the maximum density predicted by Miller and Bakken (1972), suggesting that initiation of polymerases of DNA is a limiting factor in the control of transcription. Rates of elongation of polymerases in vitro are severely impaired, indicative of a loss of elongation factors during nuclear isolation. After 6 hr of estradiol treatment in vivo, the level of form A enzymes in ovoduct nuclei increases to 5 x 103; little change in the number of form B enzymes is seen.", "contents": "Quantitation of elongating form A and B RNA polymerases in chick oviduct nuclei and effects of estradiol. The number of elongating form A and B RNA polymerases in chick oviduct nuclei was estimated by measuring incorportaion of 3H-UTP into 3' termini of nascent RNA chains in the presence of heparin to inhibit initiation, and quantitation labeled uridine released from these termini after alkaline hydrolysis. The method corrects for conversion of UMP to uridine (U) during manipulations and for production of 3' termini by ribonucleases and phosphatases. The results indicate that a large fraction of RNA polymerases elongating in vivo is retained in isolated nuclei: per diploid genome, approximately 1 x104 form B and 2 x103 form A enzymes are present. These levels are sufficient to maintain normal in vivo rates of mRNA and rRNA synthesis, but the average density of packing of polymerases on DNA is considerably less than the maximum density predicted by Miller and Bakken (1972), suggesting that initiation of polymerases of DNA is a limiting factor in the control of transcription. Rates of elongation of polymerases in vitro are severely impaired, indicative of a loss of elongation factors during nuclear isolation. After 6 hr of estradiol treatment in vivo, the level of form A enzymes in ovoduct nuclei increases to 5 x 103; little change in the number of form B enzymes is seen."} {"id": "PMID:181156", "title": "[Lysis of Rous sarcoma virus in the presence of anti-chicken fibroblast serum and complement].", "content": "Rous sarcoma virus produced by Chick embryo fibroblasts is inactivated by an antiserum prepared against uninfected fibroblasts in the presence, but not in the absence, of complement. This inactivation which demonstrates the presence of one or more antigens of the surface of the producer cell on the viral envelope, is due to virolysis. This is demonstrated by the release of the viral internal proteins and by the fact that the viral RNA becomes entirely degradable by RNase.", "contents": "[Lysis of Rous sarcoma virus in the presence of anti-chicken fibroblast serum and complement]. Rous sarcoma virus produced by Chick embryo fibroblasts is inactivated by an antiserum prepared against uninfected fibroblasts in the presence, but not in the absence, of complement. This inactivation which demonstrates the presence of one or more antigens of the surface of the producer cell on the viral envelope, is due to virolysis. This is demonstrated by the release of the viral internal proteins and by the fact that the viral RNA becomes entirely degradable by RNase."} {"id": "PMID:181157", "title": "[Induction of endogenous C-type virus by 5-iododeoxyuridine and augmentation of this induction by polycyclic hydrocarbons].", "content": "When the MLg Mouse cells were treated with the chemical carcinogens, in the presence of microsomal enzymes and NADPH2 after 5-iododeoxyuridine (IUdR) treatment, the induction frequency of the endogenous C-type virus was increased by nearly 10-fold in comparison with the cultures treated with IUdR only. In the preliminary screening of several polycyclic hydrocarbons including carcinogenic and non-carcinogenic products, apparently there was no correlation between the carcinogenecity in vivo and the stimulation capacity of IUdR induced C-type virus activation in our test conditions.", "contents": "[Induction of endogenous C-type virus by 5-iododeoxyuridine and augmentation of this induction by polycyclic hydrocarbons]. When the MLg Mouse cells were treated with the chemical carcinogens, in the presence of microsomal enzymes and NADPH2 after 5-iododeoxyuridine (IUdR) treatment, the induction frequency of the endogenous C-type virus was increased by nearly 10-fold in comparison with the cultures treated with IUdR only. In the preliminary screening of several polycyclic hydrocarbons including carcinogenic and non-carcinogenic products, apparently there was no correlation between the carcinogenecity in vivo and the stimulation capacity of IUdR induced C-type virus activation in our test conditions."} {"id": "PMID:181158", "title": "[Prospective epidemiologic studies and the nature of the association between Epstein-Barr virus (EBV) and Burkitt's lymphoma (BL)].", "content": "The prospective study carried out by the International Agency for Research on Cancer on the relationships between E.B.V. infection and Burkitt's Lymphoma development as well as their partial malaria chemoprophylaxy proposals, are discussed as an example of studying the role of a virus and of co-factors in one human cancer.", "contents": "[Prospective epidemiologic studies and the nature of the association between Epstein-Barr virus (EBV) and Burkitt's lymphoma (BL)]. The prospective study carried out by the International Agency for Research on Cancer on the relationships between E.B.V. infection and Burkitt's Lymphoma development as well as their partial malaria chemoprophylaxy proposals, are discussed as an example of studying the role of a virus and of co-factors in one human cancer."} {"id": "PMID:181159", "title": "[Absence of relationship between erythrocyte and viral antigen expressed on the surface of chick erythrocytes].", "content": "Anti-gs antisera were tested on embryo and adult Chick erythrocytes. Specific immunsera directed against Chick embryo or adult erythrocyte antigens have been tested on Hamster cell lines infected with the Rous virus. Results demonstrate that the erythrocyte and viral antigens are different.", "contents": "[Absence of relationship between erythrocyte and viral antigen expressed on the surface of chick erythrocytes]. Anti-gs antisera were tested on embryo and adult Chick erythrocytes. Specific immunsera directed against Chick embryo or adult erythrocyte antigens have been tested on Hamster cell lines infected with the Rous virus. Results demonstrate that the erythrocyte and viral antigens are different."} {"id": "PMID:181160", "title": "[Increased transmission at electronic synapses and paroxysmal depolarization induced by cardiazol in the Mauthner cell].", "content": "Cardiazol induces in the Mauthner cell the paroxysmal depolarizing shifts which are characteristic of epilepsia at the neuronal level. The period of depolarizations is preceded and, later, accompanied by an increased transmission at the electrotonic synapses which are established upon this neuron by primary afferent vestibular fibers. Increased excitability of the chemical synapses occurs subsequently.", "contents": "[Increased transmission at electronic synapses and paroxysmal depolarization induced by cardiazol in the Mauthner cell]. Cardiazol induces in the Mauthner cell the paroxysmal depolarizing shifts which are characteristic of epilepsia at the neuronal level. The period of depolarizations is preceded and, later, accompanied by an increased transmission at the electrotonic synapses which are established upon this neuron by primary afferent vestibular fibers. Increased excitability of the chemical synapses occurs subsequently."} {"id": "PMID:181161", "title": "[Phosphorylase activity of human placenta perfused in vitro: effect of gonadotropins, dibutyryl cyclic AMP and prostaglandins].", "content": "The gonadotropic hormones stimulate the glycogen phosphorylase activity of human full-term placenta perfused in vitro. This effect is reproduced by dibutyryl cAMP and PG F2alpha and accompanied by an increased glucose liberation in the perfusion fluid.", "contents": "[Phosphorylase activity of human placenta perfused in vitro: effect of gonadotropins, dibutyryl cyclic AMP and prostaglandins]. The gonadotropic hormones stimulate the glycogen phosphorylase activity of human full-term placenta perfused in vitro. This effect is reproduced by dibutyryl cAMP and PG F2alpha and accompanied by an increased glucose liberation in the perfusion fluid."} {"id": "PMID:181162", "title": "Modification by prostaglandins E1 and E2, indomethacin, and arachidonic acid of the vasoconstrictor responses of the isolated perfused rabbit and rat mesenteric arteries to adrenergic stimuli.", "content": "In isolated perfused rabbit mesenteric arteries, prostaglandin (PG) E1 and E2, 1-5NG/ML, did not alter the basal perfusion pressure, but reduced the vasoconstrictor responses to sympathetic nerve stimulation; the responses to injected norepinephrine were reduced by PGE1 and variably affected by PGE2. In contrast, in rat mesenteric arteries PGE1 and PGE2, 1-5 ng/ml, potentiated the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. In rabbit mesenteric arteries, the inhibitor of PG synthesis, indomethacin, augmented the responses to sympathetic nerve stimulation and to injected norepinephrine, whereas in rat mesenteric arteries indomethacin inhibited the responses to both adrenergic stimuli. Arachidonic acid, a PG precursor, reduced the vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine in rabbit, whereas in rat, potentiation of the responses to adrenergic stimuli occurred. Since these effects of arachidonic acid were abolished by the simultaneous infusion of indomethacin, they appear to be mediated through conversion of arachidonic acid to PG. We conclude that prostaglandins modulate adrenergic transmission in mesenteric arteries and this effect is species dependent.", "contents": "Modification by prostaglandins E1 and E2, indomethacin, and arachidonic acid of the vasoconstrictor responses of the isolated perfused rabbit and rat mesenteric arteries to adrenergic stimuli. In isolated perfused rabbit mesenteric arteries, prostaglandin (PG) E1 and E2, 1-5NG/ML, did not alter the basal perfusion pressure, but reduced the vasoconstrictor responses to sympathetic nerve stimulation; the responses to injected norepinephrine were reduced by PGE1 and variably affected by PGE2. In contrast, in rat mesenteric arteries PGE1 and PGE2, 1-5 ng/ml, potentiated the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. In rabbit mesenteric arteries, the inhibitor of PG synthesis, indomethacin, augmented the responses to sympathetic nerve stimulation and to injected norepinephrine, whereas in rat mesenteric arteries indomethacin inhibited the responses to both adrenergic stimuli. Arachidonic acid, a PG precursor, reduced the vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine in rabbit, whereas in rat, potentiation of the responses to adrenergic stimuli occurred. Since these effects of arachidonic acid were abolished by the simultaneous infusion of indomethacin, they appear to be mediated through conversion of arachidonic acid to PG. We conclude that prostaglandins modulate adrenergic transmission in mesenteric arteries and this effect is species dependent."} {"id": "PMID:181163", "title": "Influence of 5- and 6-hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed.", "content": "We studied the effects of 5- and 6-hydroxydopamine on adrenergic neurotransmission, fluorescence histochemistry, and nerve terminal ultrastructure in the canine pulmonary vascular bed. Fluorescence histochemistry on stretched preparations and sections of intrapulmonary artery and vein demonstrated that these vessels are well supplied with adrenergic nerves electron microscopy revealed adrenergic terminals in the adventitia and outer third of the media in the artery, but only in the adventitia in the vein. Adrenergic terminals in artery and vein contained many small and a few large dense-core vesicles. At least 20% of the terminals in the artery contained many small agranular vesicles and a few large opaque vesicles; this suggests that they were of the cholinergic type; Such terminals were not found in intrapulmonary veins. Under conditions of controlled blood flow, stimulation of the sympathetic nerves to the lung and intralobar injection of norepinephrine increased pressure in the perfused lobar artery and small intrapulmonary vein in a stimulus-related manner. The rise in pressure in the lobar artery and vein in response to nerve stimulation was blocked after administration of either 5- and 6-hydroxydopamine; Neither agent modified the response of the pulmonary vascular bed to norepinephrine; In contrast, the rise in pressure in the lobar artery and vein in response to both norepinephrine and to nerve stimulation was blocked by phenoxybenzamine, an alpha-receptor blocking agent. The attenuated neurogenic vasoconstrictor response in dogs treated with 5- and 6-hydroxydopamine was associated with a marked decrease in intensity of fluorescence of the abundant adrenergic innervation in both intrapulmonary artery and vein, and with the appearance of an osmiophilic material in dense-core vesicles of adrenergic terminals in artery and vein. We believe that these data suggest that 5- and 6-hydroxydopamine interfere with adrenergic transmission in intrapulmonary vessels by depleting norepinephrine from adrenergic terminals. Furthermore, we conclude from hemodynamic, histochemical, and ultrastructural studies that vasomotor tone in the pulmonary vascular bed can be regulated by the sympathetic nervous system.", "contents": "Influence of 5- and 6-hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed. We studied the effects of 5- and 6-hydroxydopamine on adrenergic neurotransmission, fluorescence histochemistry, and nerve terminal ultrastructure in the canine pulmonary vascular bed. Fluorescence histochemistry on stretched preparations and sections of intrapulmonary artery and vein demonstrated that these vessels are well supplied with adrenergic nerves electron microscopy revealed adrenergic terminals in the adventitia and outer third of the media in the artery, but only in the adventitia in the vein. Adrenergic terminals in artery and vein contained many small and a few large dense-core vesicles. At least 20% of the terminals in the artery contained many small agranular vesicles and a few large opaque vesicles; this suggests that they were of the cholinergic type; Such terminals were not found in intrapulmonary veins. Under conditions of controlled blood flow, stimulation of the sympathetic nerves to the lung and intralobar injection of norepinephrine increased pressure in the perfused lobar artery and small intrapulmonary vein in a stimulus-related manner. The rise in pressure in the lobar artery and vein in response to nerve stimulation was blocked after administration of either 5- and 6-hydroxydopamine; Neither agent modified the response of the pulmonary vascular bed to norepinephrine; In contrast, the rise in pressure in the lobar artery and vein in response to both norepinephrine and to nerve stimulation was blocked by phenoxybenzamine, an alpha-receptor blocking agent. The attenuated neurogenic vasoconstrictor response in dogs treated with 5- and 6-hydroxydopamine was associated with a marked decrease in intensity of fluorescence of the abundant adrenergic innervation in both intrapulmonary artery and vein, and with the appearance of an osmiophilic material in dense-core vesicles of adrenergic terminals in artery and vein. We believe that these data suggest that 5- and 6-hydroxydopamine interfere with adrenergic transmission in intrapulmonary vessels by depleting norepinephrine from adrenergic terminals. Furthermore, we conclude from hemodynamic, histochemical, and ultrastructural studies that vasomotor tone in the pulmonary vascular bed can be regulated by the sympathetic nervous system."} {"id": "PMID:181164", "title": "Myocardial tissue recruitment in the dog as determined by double tracer dilution method.", "content": "The amount of tissue perfused, as determined from the difference in volume of distribution between a diffusible indicator (125I-antipyrine) and an intravascular indicator (131 I-albumin) was measured at different values of coronary flow, perfusion pressure, and vasomotor tone in the working left ventricle of an open-chest dog. Coronary pressure and flow were regulated independently from the systemic circulation and coronary vasomotor tone was reduced by dipyridamole. At each flow vasomotor tone was assessed by using as a reference the maximal vasodilation induced by arrest of flow. Measured tissue space was considered to be related to the capillary surface area available for tracer diffusion and therefore to the number of perfused capillaries per volume of muscle. A relationship between coronary blood flow and tissue volume was observed. It was found to be independent of vasomotor tone. Vasodilation was found to increase available exchanging capillary surface at a constant perfusion pressure.", "contents": "Myocardial tissue recruitment in the dog as determined by double tracer dilution method. The amount of tissue perfused, as determined from the difference in volume of distribution between a diffusible indicator (125I-antipyrine) and an intravascular indicator (131 I-albumin) was measured at different values of coronary flow, perfusion pressure, and vasomotor tone in the working left ventricle of an open-chest dog. Coronary pressure and flow were regulated independently from the systemic circulation and coronary vasomotor tone was reduced by dipyridamole. At each flow vasomotor tone was assessed by using as a reference the maximal vasodilation induced by arrest of flow. Measured tissue space was considered to be related to the capillary surface area available for tracer diffusion and therefore to the number of perfused capillaries per volume of muscle. A relationship between coronary blood flow and tissue volume was observed. It was found to be independent of vasomotor tone. Vasodilation was found to increase available exchanging capillary surface at a constant perfusion pressure."} {"id": "PMID:181165", "title": "An echocardiographic study of interventricular septal motion in the Wolff-Parkinson-White syndrome.", "content": "Echocardiographic studies of interventricular septal motion were performed in 26 consecutive patients with the Wolff-Parkinson-White (WPW) syndrome and in ten normal subjects. All patients with types A or B pre-excitation were subclassified into groups I to IV on the basis of their electrocardiogram utilizing the method of Boineau and associates. In all 14 patients with type A (Group III or IV) pre-excitation, the motion of the interventricular septum and posterior left ventricular wall motion were normal. However, in 11 patients with type B (Group I) WPW an abnormal septal movement was noted. This was characterized in ten patients by an early systolic posterior motion, a subsequent anterior movement in mid systole, and the usual posterior septal motion beginning in late systole. In eight patients, including the one without early systolic posterior movement of the septum, the late systolic posterior movement was interrupted by a prominent septal notch. On e patient with type B (Group II) WPW was studied and exhibited normal septal and posterior wall motion. In one patient with a spontaneous change in the QRS complex from normal to a type B (Group I) WPW pattern, the septal motion was initially normal and abruptly changed following the first WPW beat. The onset of abnormal interventricular septal motion with type B pre-excitation QRS complexes strongly suggests that abnormal septal movement may be related to an altered sequence of ventricular depolarization during right ventricular pre-excitation.", "contents": "An echocardiographic study of interventricular septal motion in the Wolff-Parkinson-White syndrome. Echocardiographic studies of interventricular septal motion were performed in 26 consecutive patients with the Wolff-Parkinson-White (WPW) syndrome and in ten normal subjects. All patients with types A or B pre-excitation were subclassified into groups I to IV on the basis of their electrocardiogram utilizing the method of Boineau and associates. In all 14 patients with type A (Group III or IV) pre-excitation, the motion of the interventricular septum and posterior left ventricular wall motion were normal. However, in 11 patients with type B (Group I) WPW an abnormal septal movement was noted. This was characterized in ten patients by an early systolic posterior motion, a subsequent anterior movement in mid systole, and the usual posterior septal motion beginning in late systole. In eight patients, including the one without early systolic posterior movement of the septum, the late systolic posterior movement was interrupted by a prominent septal notch. On e patient with type B (Group II) WPW was studied and exhibited normal septal and posterior wall motion. In one patient with a spontaneous change in the QRS complex from normal to a type B (Group I) WPW pattern, the septal motion was initially normal and abruptly changed following the first WPW beat. The onset of abnormal interventricular septal motion with type B pre-excitation QRS complexes strongly suggests that abnormal septal movement may be related to an altered sequence of ventricular depolarization during right ventricular pre-excitation."} {"id": "PMID:181166", "title": "Correlation of pathologic Q waves on the standard electrocardiogram and the epicardial electrogram of the human heart.", "content": "To evaluate the relationship between abnormal Q waves on the standard ECG and localized ventricular excitation, unipolar epicardial electrograms were recorded over the left ventricle during aortocoronary bypass surgery in 36 patients. Of 20 without standard ECG Q waves, six had abnormal epicardial Q waves, three anterioly and three inferiorly. Of 16 patients with standard ECG Q waves, four had both precordial and anterior epicardial Q waves while seven had Q waves in leads III and aVF and inferior epicardial Q waves. Three of the 14 had Q waves in both precordial and inferior leads of the ECG but epicardial Q waves only from the antero-apical region in two and only from the inferior wall in one. Two patients with Q waves in both III and aVF had no epicardial Q waves. Thus, the standard electocardiogram underestimates epicardial Q waves. If Q waves are present in the standard ECG, they correlate with the presence, although not invariably the location of Q waves on the epicardial electrogram.", "contents": "Correlation of pathologic Q waves on the standard electrocardiogram and the epicardial electrogram of the human heart. To evaluate the relationship between abnormal Q waves on the standard ECG and localized ventricular excitation, unipolar epicardial electrograms were recorded over the left ventricle during aortocoronary bypass surgery in 36 patients. Of 20 without standard ECG Q waves, six had abnormal epicardial Q waves, three anterioly and three inferiorly. Of 16 patients with standard ECG Q waves, four had both precordial and anterior epicardial Q waves while seven had Q waves in leads III and aVF and inferior epicardial Q waves. Three of the 14 had Q waves in both precordial and inferior leads of the ECG but epicardial Q waves only from the antero-apical region in two and only from the inferior wall in one. Two patients with Q waves in both III and aVF had no epicardial Q waves. Thus, the standard electocardiogram underestimates epicardial Q waves. If Q waves are present in the standard ECG, they correlate with the presence, although not invariably the location of Q waves on the epicardial electrogram."} {"id": "PMID:181167", "title": "The His-Purkinje electrocardiogram in man: an initial assessment of its uses and limitations.", "content": "A methodology is described for noninvasive recording of the electrical activity generated by the His-Purkinje system of man utilizing filtering, high amplification, and signal averaging. A waveform ranging between 1 and 10mu V was observed during the P-R segment. In many individuals, there was temporal overlap between the terminal P wave and the initial portion of the His-Purkinje waveform. In ten patients with long P-R intervals there was a strong correlation (r greater than 0.95) between the H-V time measured by electrode catheter and the duration of the His-Purkinje waveform. In two patients with atrial fibrillation the resultant His-Purkinje waveform was similar in morphology and duration to those observed in the ten patients. In each group H-V time was determined noninvasively and a waveform associated with electrical activation of the major portions of the His-Purkinje system was obtained.", "contents": "The His-Purkinje electrocardiogram in man: an initial assessment of its uses and limitations. A methodology is described for noninvasive recording of the electrical activity generated by the His-Purkinje system of man utilizing filtering, high amplification, and signal averaging. A waveform ranging between 1 and 10mu V was observed during the P-R segment. In many individuals, there was temporal overlap between the terminal P wave and the initial portion of the His-Purkinje waveform. In ten patients with long P-R intervals there was a strong correlation (r greater than 0.95) between the H-V time measured by electrode catheter and the duration of the His-Purkinje waveform. In two patients with atrial fibrillation the resultant His-Purkinje waveform was similar in morphology and duration to those observed in the ten patients. In each group H-V time was determined noninvasively and a waveform associated with electrical activation of the major portions of the His-Purkinje system was obtained."} {"id": "PMID:181168", "title": "Electrophysiological studies in patients with chronic recurrent ventricular tachycardia.", "content": "Seventeen consecutive patients with chronic recurrent ventricular tachycardia (VT) were studied in an attempt to delineate the reproducibility and mechanism of this arrhythmia. Six patients had nonsustained and 11 had sustained VT. The following electrophysiological techniques were utilized in an attempt to reproduce VT: 1) rapid atrial and ventricular pacing (17 pts); 2) atrial extrastimulus technique (17 pts); 3) ventricular extrastimulus technique (17 pts); 4) V1V2V3 stimulation technique (5 pts); 5) ventricular pacing from two or more sites (5 pts). Ventricular tachycardia was induced in six of 11 (54%) patients with sustained VT. However, in four there was only a single induction and only in the remaining two patients could VT be repetitively induced. In the latter two patients ventricular tachycardia was induced with both atrial and ventricular stimulation. Ventricular tachycardia could not be induced in any patient with nonsustained VT, although three had spontaneous episodes of ventricular tachycardia during study. In conclusion, in the present series of patients with chronic recurrent VT, this rhythm could not be reproducibly induced in the majority of patients in the cardiac catheterization laboratory utilizing catheter stimulation techniques.", "contents": "Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Seventeen consecutive patients with chronic recurrent ventricular tachycardia (VT) were studied in an attempt to delineate the reproducibility and mechanism of this arrhythmia. Six patients had nonsustained and 11 had sustained VT. The following electrophysiological techniques were utilized in an attempt to reproduce VT: 1) rapid atrial and ventricular pacing (17 pts); 2) atrial extrastimulus technique (17 pts); 3) ventricular extrastimulus technique (17 pts); 4) V1V2V3 stimulation technique (5 pts); 5) ventricular pacing from two or more sites (5 pts). Ventricular tachycardia was induced in six of 11 (54%) patients with sustained VT. However, in four there was only a single induction and only in the remaining two patients could VT be repetitively induced. In the latter two patients ventricular tachycardia was induced with both atrial and ventricular stimulation. Ventricular tachycardia could not be induced in any patient with nonsustained VT, although three had spontaneous episodes of ventricular tachycardia during study. In conclusion, in the present series of patients with chronic recurrent VT, this rhythm could not be reproducibly induced in the majority of patients in the cardiac catheterization laboratory utilizing catheter stimulation techniques."} {"id": "PMID:181169", "title": "Observations on mechanisms of ventricular tachycardia in man.", "content": "Fifty patients with sustained ventricular tachycardia were studied by endocavitary recordings and programmed electrical stimulation. Of 29 patients in whom tachycardia could be initiated, 18 had chronic coronary artery disease and eight had no detectable heart disease. Of 35 patients in whom the tachycardia could be terminated by premature ventricular stimuli, 21 had chronic coronary artery disease and eight had no detectable heart disease. Initiation of tachycardia was facilitated in 18 of 21 patients by pacing the ventricle at the slowest possible pacing rate. An inverse relation was found between the prematurity of the tachycardia-initiating premature beat and the interval between the premature beat and the first beat of tachycardia, a finding suggestive of a re-entry mechanism. The role of the specific conduction system in initiation and during tachycardia remains unknown. Stimulation site was found to affect initiation and termination of tachycardia and width of tachycardia zone.", "contents": "Observations on mechanisms of ventricular tachycardia in man. Fifty patients with sustained ventricular tachycardia were studied by endocavitary recordings and programmed electrical stimulation. Of 29 patients in whom tachycardia could be initiated, 18 had chronic coronary artery disease and eight had no detectable heart disease. Of 35 patients in whom the tachycardia could be terminated by premature ventricular stimuli, 21 had chronic coronary artery disease and eight had no detectable heart disease. Initiation of tachycardia was facilitated in 18 of 21 patients by pacing the ventricle at the slowest possible pacing rate. An inverse relation was found between the prematurity of the tachycardia-initiating premature beat and the interval between the premature beat and the first beat of tachycardia, a finding suggestive of a re-entry mechanism. The role of the specific conduction system in initiation and during tachycardia remains unknown. Stimulation site was found to affect initiation and termination of tachycardia and width of tachycardia zone."} {"id": "PMID:181170", "title": "Body-surface maps of heart potentials: tentative localization of pre-excited areas in forty-two Wolff-Parkinson-White patients.", "content": "Heart potentials were recorded from the entire chest surface in 42 patients suffering from Wolff-Parkinson-White syndrome. We were able to identify six types of surface maps, according to the location of the potential maximum and minimum during the delta wave. For each of these types we suggested the most likely location of the pre-excited region around the A-V rings (types 1 to 5) or in the interventricular septum (type 6). In 13 patients belonging to Types 1, 2, 3, 5 and 6 our hypotheses were in agreement with intracardiac recordings, epicardial maps or surgical results obtained by others. Isopotential surface maps provide more information on the location of the pre-excited area than conventional ECGs, particularly when these exhibit intermediate features between Types A and B.", "contents": "Body-surface maps of heart potentials: tentative localization of pre-excited areas in forty-two Wolff-Parkinson-White patients. Heart potentials were recorded from the entire chest surface in 42 patients suffering from Wolff-Parkinson-White syndrome. We were able to identify six types of surface maps, according to the location of the potential maximum and minimum during the delta wave. For each of these types we suggested the most likely location of the pre-excited region around the A-V rings (types 1 to 5) or in the interventricular septum (type 6). In 13 patients belonging to Types 1, 2, 3, 5 and 6 our hypotheses were in agreement with intracardiac recordings, epicardial maps or surgical results obtained by others. Isopotential surface maps provide more information on the location of the pre-excited area than conventional ECGs, particularly when these exhibit intermediate features between Types A and B."} {"id": "PMID:181171", "title": "Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study.", "content": "Serum lipoprotein profiles in 3182 children, ages 5-14 years, were studied in a biracial community as part of the Bogalusa Heart Study to describe the early natural history of atherosclerosis. White and black children showed similar mean levels of beta-lipoproteins. Pre-beta-lipoprotein levels, however, were significantly higher in white shildren, while significantly higher levels of alpha-lipoprotein were found in black children. Girls had generally higher levels of beta- and pre-beta-lipoprotein and lower levels of alpha-lipoprotein than boys, although the differences were not significant at each age group. With age there was little change in alpha-lipoprotein levels, a significant increase in pre-beta-lipoprotein levels and a slight but significant decrease between 11 and 14 years in beta-lipoprotein levels. The correlation of alpha-lipoprotein was negative with beta-lipoprotein and, to a greater extent, with pre-beta-lipoprotein. The above inverse relationships were significantly greater in white children than in black children, suggesting differences in lipoprotein profiles in the two groups. Lipoprotein values from a total community study are now available for comparison with the currently recommended upper normal limits for lipoproteins. Since only a very small percentage of children could be considered as hyperlipoproteinemic by those specific levels in this community, we suggest that distributions and percentiles be used to evaluate children for hyperlipoproteinemia.", "contents": "Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study. Serum lipoprotein profiles in 3182 children, ages 5-14 years, were studied in a biracial community as part of the Bogalusa Heart Study to describe the early natural history of atherosclerosis. White and black children showed similar mean levels of beta-lipoproteins. Pre-beta-lipoprotein levels, however, were significantly higher in white shildren, while significantly higher levels of alpha-lipoprotein were found in black children. Girls had generally higher levels of beta- and pre-beta-lipoprotein and lower levels of alpha-lipoprotein than boys, although the differences were not significant at each age group. With age there was little change in alpha-lipoprotein levels, a significant increase in pre-beta-lipoprotein levels and a slight but significant decrease between 11 and 14 years in beta-lipoprotein levels. The correlation of alpha-lipoprotein was negative with beta-lipoprotein and, to a greater extent, with pre-beta-lipoprotein. The above inverse relationships were significantly greater in white children than in black children, suggesting differences in lipoprotein profiles in the two groups. Lipoprotein values from a total community study are now available for comparison with the currently recommended upper normal limits for lipoproteins. Since only a very small percentage of children could be considered as hyperlipoproteinemic by those specific levels in this community, we suggest that distributions and percentiles be used to evaluate children for hyperlipoproteinemia."} {"id": "PMID:181172", "title": "Cardioversion and \"false positive\" technetium-99m stannous pyrophosphate myocardial scintigrams.", "content": "The present studies performed in experimental animals demonstrate that electrical direct current cardioversion can produce skeletal muscle damage and increased technetium-99m stannous pyrophosphate (99mTc-PYP) uptake; in experimental animals the electrically damaged skeletal muscle shows necrosis with extensive calcium deposition. In addition, the frequent administration of high energy cardioversion produces myocardial necrosis with calcium deposition, increased 99mTc-PYP myocardial uptake and a positive 99mTc-PYP myocardial scintigram. The data indicate that, if diagnostic 99mTc-PYP myocardial scintigraphy is contemplated after cardioversion, paddle placement should be slightly removed from the anteroposterior projection of the heart on the external chest wall to avoid possible subsequent confusion between increased myocardial and skeletal muscle uptake of 99mTc-PYP. If multiple high energy cardioversion episodes are necessary, myocardial necrosis resulting from electrical injury may occur and be responisble for increased myocardial uptake of 99mTc-PYP with a resultant positive 99mTc-PYP myocardial scintigram.", "contents": "Cardioversion and \"false positive\" technetium-99m stannous pyrophosphate myocardial scintigrams. The present studies performed in experimental animals demonstrate that electrical direct current cardioversion can produce skeletal muscle damage and increased technetium-99m stannous pyrophosphate (99mTc-PYP) uptake; in experimental animals the electrically damaged skeletal muscle shows necrosis with extensive calcium deposition. In addition, the frequent administration of high energy cardioversion produces myocardial necrosis with calcium deposition, increased 99mTc-PYP myocardial uptake and a positive 99mTc-PYP myocardial scintigram. The data indicate that, if diagnostic 99mTc-PYP myocardial scintigraphy is contemplated after cardioversion, paddle placement should be slightly removed from the anteroposterior projection of the heart on the external chest wall to avoid possible subsequent confusion between increased myocardial and skeletal muscle uptake of 99mTc-PYP. If multiple high energy cardioversion episodes are necessary, myocardial necrosis resulting from electrical injury may occur and be responisble for increased myocardial uptake of 99mTc-PYP with a resultant positive 99mTc-PYP myocardial scintigram."} {"id": "PMID:181173", "title": "Paroxysmal supraventricular tachycardia: is the atrium a necessary link?", "content": "Whether or not the atrium plays an essential role in initiating and/or sustaining atrioventricular (A-V) nodal re-entrant tachycardia was evaluated in eight patients. In all eight patients, the atrium could be rendered refractory to retrograde atrial echoes during the tachycardia without interrupting the arrhythmia. This was accomplished by introducing atrial premature depolarizations prior to the time the atrium would normally be retrogradely depolarized by atrial echoes. In one patient, two atrial premature depolarizations could be introduced, producing A-V dissociation, without terminating the tachycardia. In another patient, the tachycardia could be initiated without an atrial echo. Our data suggest that most, if not all of the atrium is unnecessary for the initiation and maintenance of A-V nodal re-entrant supraventricular tachycardia.", "contents": "Paroxysmal supraventricular tachycardia: is the atrium a necessary link? Whether or not the atrium plays an essential role in initiating and/or sustaining atrioventricular (A-V) nodal re-entrant tachycardia was evaluated in eight patients. In all eight patients, the atrium could be rendered refractory to retrograde atrial echoes during the tachycardia without interrupting the arrhythmia. This was accomplished by introducing atrial premature depolarizations prior to the time the atrium would normally be retrogradely depolarized by atrial echoes. In one patient, two atrial premature depolarizations could be introduced, producing A-V dissociation, without terminating the tachycardia. In another patient, the tachycardia could be initiated without an atrial echo. Our data suggest that most, if not all of the atrium is unnecessary for the initiation and maintenance of A-V nodal re-entrant supraventricular tachycardia."} {"id": "PMID:181174", "title": "Analysis of surgically-induced right bundle branch block pattern using intracardiac recording techniques.", "content": "Using intracardiac recording techniques, His bundle (H) and right ventricular apical (RVA) electrograms were recorded in 16 patients with a postoperative electrocardiographic pattern of right bundle branch block (RBBB). Their ages ranged from 5 to 12 years (mean 6.9 years) at surgery and the follow-up period was 1 to 7 years (mean 2.7 years). All were asymptomatic and in sinus rhythm at the time of study. The P-A interval was normal in all and the A-H, H-V, and V-RVA intervals were prolonged in one, one, and six patients, respectively. The V-RNA interval was normal (less than or equal to 30 msec) in ten out of the 11 patients (91%) without associated left anterior hemiblock (LAH), indicating a physiologically intact main right bundle branch, and was abnormally lengthened (45-62 msec) in all five patients (100%) with associated LAH. These findings suggest that there are two subgroups of patients with surgicall-induced RBBB pattern and the measurement of the V-RVA interval in conjunction with the H-V interval may be of ultimate importance in understanding the long-term prognostic implication of surgically-induced RBBB pattern with or without LAH.", "contents": "Analysis of surgically-induced right bundle branch block pattern using intracardiac recording techniques. Using intracardiac recording techniques, His bundle (H) and right ventricular apical (RVA) electrograms were recorded in 16 patients with a postoperative electrocardiographic pattern of right bundle branch block (RBBB). Their ages ranged from 5 to 12 years (mean 6.9 years) at surgery and the follow-up period was 1 to 7 years (mean 2.7 years). All were asymptomatic and in sinus rhythm at the time of study. The P-A interval was normal in all and the A-H, H-V, and V-RVA intervals were prolonged in one, one, and six patients, respectively. The V-RNA interval was normal (less than or equal to 30 msec) in ten out of the 11 patients (91%) without associated left anterior hemiblock (LAH), indicating a physiologically intact main right bundle branch, and was abnormally lengthened (45-62 msec) in all five patients (100%) with associated LAH. These findings suggest that there are two subgroups of patients with surgicall-induced RBBB pattern and the measurement of the V-RVA interval in conjunction with the H-V interval may be of ultimate importance in understanding the long-term prognostic implication of surgically-induced RBBB pattern with or without LAH."} {"id": "PMID:181175", "title": "Earlier onset of QRS in anterior precordial ECG leads: precision of time interval measurements.", "content": "Onset of QRS was compared between simultaneously recorded conventional ECG leads in 84 subjects with clinically normal hearts from a defined population sample. Mean onset of QRS was 6.4 msec earlier in lead V1 and 7.4 msec earlier in V2 than in lead II. These differences were statistically significant. The measuring system was adapted from drafting techniques and took into account variations in paper speed which occurred during recording. Interobserver differences equivalent to greater than 1 msec occurred in 3.9% of timeline measurements, but in in 38% of QRS onset measurements. The lower precision in measuring QRS onset may be attributed to baseline oscillations and to the relatively slow rate of voltage change at the onset of ventricular depolarization.", "contents": "Earlier onset of QRS in anterior precordial ECG leads: precision of time interval measurements. Onset of QRS was compared between simultaneously recorded conventional ECG leads in 84 subjects with clinically normal hearts from a defined population sample. Mean onset of QRS was 6.4 msec earlier in lead V1 and 7.4 msec earlier in V2 than in lead II. These differences were statistically significant. The measuring system was adapted from drafting techniques and took into account variations in paper speed which occurred during recording. Interobserver differences equivalent to greater than 1 msec occurred in 3.9% of timeline measurements, but in in 38% of QRS onset measurements. The lower precision in measuring QRS onset may be attributed to baseline oscillations and to the relatively slow rate of voltage change at the onset of ventricular depolarization."} {"id": "PMID:181176", "title": "Treatment of a case of allergic asthma with a synthetic human ACTH preparation.", "content": "The following case history documents the first patient treated with synthetic human ACTH. It was prescribed for an asthmatic child because of suspected allergy to both porcine ACTH and tetracosactrin. It proved both effective clinically and free of any adverse effects.", "contents": "Treatment of a case of allergic asthma with a synthetic human ACTH preparation. The following case history documents the first patient treated with synthetic human ACTH. It was prescribed for an asthmatic child because of suspected allergy to both porcine ACTH and tetracosactrin. It proved both effective clinically and free of any adverse effects."} {"id": "PMID:181178", "title": "Purification and analysis of the purity of NADH.", "content": "We developed an analytical reverse-phase high-performance liquid chromatographic procedure for rapid assessment of the purity of NADH. The method completely separates adenosine monophosphate and adenosine diphosphoribose from NADH. By use of this analytical technique we found that preparative chromatography on DEAE-cellulose gives NADH that is free from adenine nucleotides as well as other impurities that commonly are present in NADH. The absorbance ratio at 260 and 340 nm of the purified NADH in 1.8 mmol/liter ammonium carbonate is 2.261 +/- 0.002 (+/- 1 SD).", "contents": "Purification and analysis of the purity of NADH. We developed an analytical reverse-phase high-performance liquid chromatographic procedure for rapid assessment of the purity of NADH. The method completely separates adenosine monophosphate and adenosine diphosphoribose from NADH. By use of this analytical technique we found that preparative chromatography on DEAE-cellulose gives NADH that is free from adenine nucleotides as well as other impurities that commonly are present in NADH. The absorbance ratio at 260 and 340 nm of the purified NADH in 1.8 mmol/liter ammonium carbonate is 2.261 +/- 0.002 (+/- 1 SD)."} {"id": "PMID:181179", "title": "Structure of some aliphatic dicarboxylic acids found in the urine of an infant with congenital lactic acidosis.", "content": "Gas chromatography/mass spectrometry was used to identify a series of acids in urine and serum from a child who died 26 h after birth in severe metabolic acidosis with high lactate excretion. cis-5-Decene-1, 10-dioic acid and cis-5-dodencene-1, 12-dioic acid were synthesized and used as references. The following acids were found: hexane-1,6-dioic acid, octane-1,8-dioic acid, decane-1,10-dioic acid, dodecane-1,12-dioic acid, cis-5-decene-1,10-dioic acid, cis-5-dodecen-1,12-dioic acid, cis-5-tetradecene-1,14-dioic acid, trans-3-decene-1,10-dioic acid, and trans-3-dodecene-1,12-dioic acid. The concentration of C6 to C14 acids in the patient's urine was 3.7 mol/mol of creatinine; it was less than 0.2 mol/mol of creatinine in eight normal newborns and approximately 0.1 mol/mol of creatinine in a case of fructose-1,6-biphosphatase deficiency with lactic acidosis. 5-cis-Dodecenedioic acid was present in highest concentration: 1 mol/mol of creatinine in urine and 61 mumol/liter in serum. We propose that impaired beta-oxidation, probably at the acyl-CoA-dehydrogenase step, resulted in the formation of the observed acids. The parents were consanguineous, and a sibling died with the same clinical picture, which suggests a genetic defect.", "contents": "Structure of some aliphatic dicarboxylic acids found in the urine of an infant with congenital lactic acidosis. Gas chromatography/mass spectrometry was used to identify a series of acids in urine and serum from a child who died 26 h after birth in severe metabolic acidosis with high lactate excretion. cis-5-Decene-1, 10-dioic acid and cis-5-dodencene-1, 12-dioic acid were synthesized and used as references. The following acids were found: hexane-1,6-dioic acid, octane-1,8-dioic acid, decane-1,10-dioic acid, dodecane-1,12-dioic acid, cis-5-decene-1,10-dioic acid, cis-5-dodecen-1,12-dioic acid, cis-5-tetradecene-1,14-dioic acid, trans-3-decene-1,10-dioic acid, and trans-3-dodecene-1,12-dioic acid. The concentration of C6 to C14 acids in the patient's urine was 3.7 mol/mol of creatinine; it was less than 0.2 mol/mol of creatinine in eight normal newborns and approximately 0.1 mol/mol of creatinine in a case of fructose-1,6-biphosphatase deficiency with lactic acidosis. 5-cis-Dodecenedioic acid was present in highest concentration: 1 mol/mol of creatinine in urine and 61 mumol/liter in serum. We propose that impaired beta-oxidation, probably at the acyl-CoA-dehydrogenase step, resulted in the formation of the observed acids. The parents were consanguineous, and a sibling died with the same clinical picture, which suggests a genetic defect."} {"id": "PMID:181180", "title": "Correlation between estrogen receptor protein and carcinoembryonic antigen in normal and carcinomatous human breast tissue.", "content": "We determined estrogen receptor protein and carcinoembryonic antigen in cytosols prepared from 189 human breast carcinoma tissues, 85 benign or normal breast biopsies, and 101 tissue specimens metastatic from breast carcinoma. Carcinoembryonic antigen was observed in 70% of the primary carcinomatous tissues, 15% of the benign or normal specimens, and 51% of the metastases. Ninety-six of the 189 primary carcinomatous specimens with increased concentrations of carcinoembryonic antigen were also positive for estrogen receptor protein, whereas 67 of the 72 benign or normal biopsies with low concentrations of carcinoembryonic antigen were also negative for estrogen receptor protein. All five fenign specimens with positive estrogen receptor protein and normal carcinoembryonic antigen concentrations were from fibroadenomas. The concordance between estrogen receptor protein and carcinoembryonic antigen in the primary carcinomatous tissue was 66%, in metastatic carcinoma 51%, and in benign and normal tissue 85%.", "contents": "Correlation between estrogen receptor protein and carcinoembryonic antigen in normal and carcinomatous human breast tissue. We determined estrogen receptor protein and carcinoembryonic antigen in cytosols prepared from 189 human breast carcinoma tissues, 85 benign or normal breast biopsies, and 101 tissue specimens metastatic from breast carcinoma. Carcinoembryonic antigen was observed in 70% of the primary carcinomatous tissues, 15% of the benign or normal specimens, and 51% of the metastases. Ninety-six of the 189 primary carcinomatous specimens with increased concentrations of carcinoembryonic antigen were also positive for estrogen receptor protein, whereas 67 of the 72 benign or normal biopsies with low concentrations of carcinoembryonic antigen were also negative for estrogen receptor protein. All five fenign specimens with positive estrogen receptor protein and normal carcinoembryonic antigen concentrations were from fibroadenomas. The concordance between estrogen receptor protein and carcinoembryonic antigen in the primary carcinomatous tissue was 66%, in metastatic carcinoma 51%, and in benign and normal tissue 85%."} {"id": "PMID:181181", "title": "End-point parameter adjustment on a small desk-top programmable calculator for logit-log analysis of radioimmunoassay data.", "content": "We describe an improved method of logit-log curve fitting, by adjusting end-point parameters in radioimmunoassay studies, for use with a small desk-top programmable calculator. Straight logit-log analyses are often deficient because of their high sensitivity to small errors in the end-point parametes B0 and NSB (the actual measured activity in the tubes). The literature suggests techniques for adjusting these end-point parameters, but they require too much computing time and programming space to be used with a desk-top programmable calculator. The extension to the logit-log model presented here is easily handled by the programmable calculator and provides a good estimate of the change required in B0 and NSB to obtain a better fit. The program requires 1.5 min to run on our desk-top programmable calculator, and has resulted in improved data analysis for all of the 11 types of radioimmunoassay studied.", "contents": "End-point parameter adjustment on a small desk-top programmable calculator for logit-log analysis of radioimmunoassay data. We describe an improved method of logit-log curve fitting, by adjusting end-point parameters in radioimmunoassay studies, for use with a small desk-top programmable calculator. Straight logit-log analyses are often deficient because of their high sensitivity to small errors in the end-point parametes B0 and NSB (the actual measured activity in the tubes). The literature suggests techniques for adjusting these end-point parameters, but they require too much computing time and programming space to be used with a desk-top programmable calculator. The extension to the logit-log model presented here is easily handled by the programmable calculator and provides a good estimate of the change required in B0 and NSB to obtain a better fit. The program requires 1.5 min to run on our desk-top programmable calculator, and has resulted in improved data analysis for all of the 11 types of radioimmunoassay studied."} {"id": "PMID:181182", "title": "Unsuitability of porcelain crucibles for dry ashing of biological tissues for calcium analysis.", "content": "At temperatures required for complete release of calcium from beef liver by dry ashing, porcelain crucibles release significant amounts of calcium into the ash, which leads to erroneously high calcium values in the samples. Heated, empty porcelain crucibles do not show released calcium. Both fused silica and platinum crucibles fail to show any significant interaction with the sample. Samples dry-ashed in fused silica crucibles were compared to samples subjected to the hot trichloracetic acid-acetic acid extraction method, which gave results not significantly different if the tissue was first minced. However, calcium was incompletely extracted by the hot acid from whole segments of liver weighing about 0.2 g.", "contents": "Unsuitability of porcelain crucibles for dry ashing of biological tissues for calcium analysis. At temperatures required for complete release of calcium from beef liver by dry ashing, porcelain crucibles release significant amounts of calcium into the ash, which leads to erroneously high calcium values in the samples. Heated, empty porcelain crucibles do not show released calcium. Both fused silica and platinum crucibles fail to show any significant interaction with the sample. Samples dry-ashed in fused silica crucibles were compared to samples subjected to the hot trichloracetic acid-acetic acid extraction method, which gave results not significantly different if the tissue was first minced. However, calcium was incompletely extracted by the hot acid from whole segments of liver weighing about 0.2 g."} {"id": "PMID:181183", "title": "Primary hyperlipoproteinemia in xanthomatosis.", "content": "Blood lipid values, clinical data and effects of therapy are reported on 74 patients with hyperlipidemia and xanthomatosis. A natural subdivision into two groups was observed on the basis of low density lipoprotein lipid values: one corresponding to Frederickson's type II, characterized by elevated low density lipoproteins, tendinous xanthomata, absence of eruptive xanthomata and a high incidence of cardiovascular diseases and the other resembling Frederickson's type III, with elevated very low density lipoproteins, eruptive xanthomata, xanthomata striata palmaria, elevated cholesterol/triglyceride ratios in the very low density lipoproteins and irregular appearance of floating beta lipoproteins. The latter group consisted of 32 patients in whom cardiovascular symptoms were relatively rare, despite mean cholesterol levels of 500 mg/dl.", "contents": "Primary hyperlipoproteinemia in xanthomatosis. Blood lipid values, clinical data and effects of therapy are reported on 74 patients with hyperlipidemia and xanthomatosis. A natural subdivision into two groups was observed on the basis of low density lipoprotein lipid values: one corresponding to Frederickson's type II, characterized by elevated low density lipoproteins, tendinous xanthomata, absence of eruptive xanthomata and a high incidence of cardiovascular diseases and the other resembling Frederickson's type III, with elevated very low density lipoproteins, eruptive xanthomata, xanthomata striata palmaria, elevated cholesterol/triglyceride ratios in the very low density lipoproteins and irregular appearance of floating beta lipoproteins. The latter group consisted of 32 patients in whom cardiovascular symptoms were relatively rare, despite mean cholesterol levels of 500 mg/dl."} {"id": "PMID:181184", "title": "Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: a new diagnostic test.", "content": "Reduction of exogenous cytochrome c was induced by the treatment of human polymorphonuclear leucocytes with cytochalasin E. The reduction was completely inhibited by superoxide, dismutase, indicating that superoxide anions were released from the cells. The leucocytes from two patients with chronic granulomatous disease did not show the release reaction that should have been brought on by the treatment. The cytochalasin-induced reduction of exogenous cytochrome c by polymorphonuclear leucocytes is so specific and sensitive that it seems to be useful for diagnosis of chronic granulomatous disease.", "contents": "Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: a new diagnostic test. Reduction of exogenous cytochrome c was induced by the treatment of human polymorphonuclear leucocytes with cytochalasin E. The reduction was completely inhibited by superoxide, dismutase, indicating that superoxide anions were released from the cells. The leucocytes from two patients with chronic granulomatous disease did not show the release reaction that should have been brought on by the treatment. The cytochalasin-induced reduction of exogenous cytochrome c by polymorphonuclear leucocytes is so specific and sensitive that it seems to be useful for diagnosis of chronic granulomatous disease."} {"id": "PMID:181185", "title": "Maternal immunoglobulins and parainfluenza 3 virus inhibitors in the nasal and lachrymal secretions and serum of newborn lambs.", "content": "Concentrations of IgG, IgM and IgA were measured in the serum, nasal secretions and lachrymal secretions of suckled newborn lambs. The major immunoglobulin constituent of precolostral serum was IgM. Maternal immunoglobulins, of which IgG was predominant, reached peak values on day 1 of life and then declined over the next 3 weeks. Half lives were calculated as: IgG, 13-7 days; IgM, 4-1 days; and IgA 1-8 days. No immunoglobulin was detectable in nasal or lachrymal secretions prior to sucking but IgG was present in all samples of these secretions obtained approximately 24 hr after first sucking. IgG was present in nasal washings from suckled lambs, reared either naturally or on immunoglobulin-free milk substitute and levels declined as the lambs grew older. IgM and IgA did not appear consistently in the secretions until lambs were 2-3 weeks old. It was concluded, therefore, that colostral IgG reaches the nasal and lachrymal secretions of the newborn lamb. However, because the ewes in this experiment had only low serum titres, no maternal antibody to parainfluenza 3 virus (PI3) was detected in the nasal secretions of the lambs, although non-specific inhibitors were present. It is suggested, however, that low levels of maternal antibody in the secretions may play a valuable role in preventing respiratory virus infections of young ruminants before active local production of IgA and IgM begins at 2 to 3 weeks of age.", "contents": "Maternal immunoglobulins and parainfluenza 3 virus inhibitors in the nasal and lachrymal secretions and serum of newborn lambs. Concentrations of IgG, IgM and IgA were measured in the serum, nasal secretions and lachrymal secretions of suckled newborn lambs. The major immunoglobulin constituent of precolostral serum was IgM. Maternal immunoglobulins, of which IgG was predominant, reached peak values on day 1 of life and then declined over the next 3 weeks. Half lives were calculated as: IgG, 13-7 days; IgM, 4-1 days; and IgA 1-8 days. No immunoglobulin was detectable in nasal or lachrymal secretions prior to sucking but IgG was present in all samples of these secretions obtained approximately 24 hr after first sucking. IgG was present in nasal washings from suckled lambs, reared either naturally or on immunoglobulin-free milk substitute and levels declined as the lambs grew older. IgM and IgA did not appear consistently in the secretions until lambs were 2-3 weeks old. It was concluded, therefore, that colostral IgG reaches the nasal and lachrymal secretions of the newborn lamb. However, because the ewes in this experiment had only low serum titres, no maternal antibody to parainfluenza 3 virus (PI3) was detected in the nasal secretions of the lambs, although non-specific inhibitors were present. It is suggested, however, that low levels of maternal antibody in the secretions may play a valuable role in preventing respiratory virus infections of young ruminants before active local production of IgA and IgM begins at 2 to 3 weeks of age."} {"id": "PMID:181186", "title": "The stimulation of lymphocytes by chondrocytes in mixed cultures.", "content": "The stimulation of lymphocytes by allogeneic and syngeneic cells other than lymphocytes has been shown to result in poor or no stimulation. We have been able to demonstrate that lymphocytes and chondrocytes mixed in culture both allogeneically and syngeneically has resulted in siginificant lymphocyte stimulation. The inference from this data suggest the presence of histocompatibility antigen as well as tissue-specific antigen on the surface of chondrocytes.", "contents": "The stimulation of lymphocytes by chondrocytes in mixed cultures. The stimulation of lymphocytes by allogeneic and syngeneic cells other than lymphocytes has been shown to result in poor or no stimulation. We have been able to demonstrate that lymphocytes and chondrocytes mixed in culture both allogeneically and syngeneically has resulted in siginificant lymphocyte stimulation. The inference from this data suggest the presence of histocompatibility antigen as well as tissue-specific antigen on the surface of chondrocytes."} {"id": "PMID:181187", "title": "Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice.", "content": "When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results.", "contents": "Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice. When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results."} {"id": "PMID:181188", "title": "Properties of blast cells in 'control' cultures of human blood lymphocytes. Preliminary note.", "content": "Ficoll-Hypaque separated normal human peripheral blood lymphocytes undergo appreciable blastogenesis in RPMI 1640-pooled human serum or - autologous plasma. During the 1st week, granulated blasts with peroixdase activity and ultrastructural properties of granulocytes precursors appear. These cells, which appear to be relateed to CFC (colony-forming cells), contribute to the mitotic population in these unstimulated \"control\" cultures prior to 6 days.", "contents": "Properties of blast cells in 'control' cultures of human blood lymphocytes. Preliminary note. Ficoll-Hypaque separated normal human peripheral blood lymphocytes undergo appreciable blastogenesis in RPMI 1640-pooled human serum or - autologous plasma. During the 1st week, granulated blasts with peroixdase activity and ultrastructural properties of granulocytes precursors appear. These cells, which appear to be relateed to CFC (colony-forming cells), contribute to the mitotic population in these unstimulated \"control\" cultures prior to 6 days."} {"id": "PMID:181189", "title": "The effects of cyclic AMP on leucocyte inhibitory factor (LIF) production and on the inhibition of leucocyte migration.", "content": "The effect of drugs known to increase intracellular levels of cyllic AMP were studied in the leucocyte migration ihibition system. It was found that cyclic AMP, dibutyryl cyclic AMP, theophyline, and prostaglandins E1 and E2 inhibited the production of leucocyte inhibiting factor by HA pulsed lymphocytes Inhibition only occured when the drugs were present during or after the PHA pulse. In addition it was found that these drugs enhanced the migration of polymorphonuclear leucocytes (PMN), in this system. Electrophoretic mobility of PMN cells was not altered by these drug indicating that the effect is not due to changes in membrane charge. However, granulocyte adhesion was reduced in the presence of these drug suggesting that adhesion is of primary importance in the migration of polymorphonuclear leucocytes out of capillary tubes. The findings show that cyclic AMP is important in modulating both cell-mediated and inflammatory responses.", "contents": "The effects of cyclic AMP on leucocyte inhibitory factor (LIF) production and on the inhibition of leucocyte migration. The effect of drugs known to increase intracellular levels of cyllic AMP were studied in the leucocyte migration ihibition system. It was found that cyclic AMP, dibutyryl cyclic AMP, theophyline, and prostaglandins E1 and E2 inhibited the production of leucocyte inhibiting factor by HA pulsed lymphocytes Inhibition only occured when the drugs were present during or after the PHA pulse. In addition it was found that these drugs enhanced the migration of polymorphonuclear leucocytes (PMN), in this system. Electrophoretic mobility of PMN cells was not altered by these drug indicating that the effect is not due to changes in membrane charge. However, granulocyte adhesion was reduced in the presence of these drug suggesting that adhesion is of primary importance in the migration of polymorphonuclear leucocytes out of capillary tubes. The findings show that cyclic AMP is important in modulating both cell-mediated and inflammatory responses."} {"id": "PMID:181190", "title": "Immunological studies of human placentae. Lectin binding to villous stroma and to trophoblastic basement membrane.", "content": "It has been demonstrated immunohistologically using cryostat sections that the lectins PHA and Con A bind to human placentae. Both lectins stain trophoblastic basement membrane (TBM), perivascular tissue and stroma. No staining of trophoblasts was observed. It has been shown by blocking experiments that the lectin binding sites on placental TBM are glycoproteins, whereas experiments involving pretreatment of placental sections with anti-collagen antisera or highly purified bacterial collagenase have indicated that lectin binding to stromal and perivascular structures is collagen-associated. The possible relation of TBM lectin-binding sites to immune response gene products is briefly discussed.", "contents": "Immunological studies of human placentae. Lectin binding to villous stroma and to trophoblastic basement membrane. It has been demonstrated immunohistologically using cryostat sections that the lectins PHA and Con A bind to human placentae. Both lectins stain trophoblastic basement membrane (TBM), perivascular tissue and stroma. No staining of trophoblasts was observed. It has been shown by blocking experiments that the lectin binding sites on placental TBM are glycoproteins, whereas experiments involving pretreatment of placental sections with anti-collagen antisera or highly purified bacterial collagenase have indicated that lectin binding to stromal and perivascular structures is collagen-associated. The possible relation of TBM lectin-binding sites to immune response gene products is briefly discussed."} {"id": "PMID:181193", "title": "Lithium treatment during alcoholic withdrawal.", "content": "The efficacy of lithium carbonate was studied in 18 chronic alcoholic male patients in withdrawal. In mild alcoholic withdrawal, oral lithium carbonate, 0.3 gm every 8 hr, diminishes subjective symptoms of withdrawal and normalizes performance on a motor tracking task. Patients who start lithium while drinking ethanol improve most probably because it takes longer than 3 days for lithium concentrations in the blood to plateau. Lithium does not importantly alter patterns of catecholamine excretion, blood pressures, heart rate, serum cyclic-adenosine monophosphate (AMP), serum dopamine beta-hydroxylase (DBH), sleep pattern, or tremor amplitude during withdrawal.", "contents": "Lithium treatment during alcoholic withdrawal. The efficacy of lithium carbonate was studied in 18 chronic alcoholic male patients in withdrawal. In mild alcoholic withdrawal, oral lithium carbonate, 0.3 gm every 8 hr, diminishes subjective symptoms of withdrawal and normalizes performance on a motor tracking task. Patients who start lithium while drinking ethanol improve most probably because it takes longer than 3 days for lithium concentrations in the blood to plateau. Lithium does not importantly alter patterns of catecholamine excretion, blood pressures, heart rate, serum cyclic-adenosine monophosphate (AMP), serum dopamine beta-hydroxylase (DBH), sleep pattern, or tremor amplitude during withdrawal."} {"id": "PMID:181194", "title": "Reversible resistance to the renal action of parathyroid hormone in man.", "content": "1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1-34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.", "contents": "Reversible resistance to the renal action of parathyroid hormone in man. 1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1-34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon."} {"id": "PMID:181197", "title": "Stimulation-induced depletion of vesicles, fatigue of transmission and recovery processes at a vertebrate central synapse.", "content": "The Mauthner fiber giant fiber synapses of the hatchetfish are chemically transmitting axo-axionic synapses in the medulla. Tetanic stimulation at room temperature depletes the presynaptic Mauthner terminal of vesicles and leads to the appearance of large numbers of irregular membraneous compartments in the terminal. Stimulation during cooling to 12 degrees C depletes the terminal of vesicles and greatly increases the external surface, which forms large whorls of invaginating double membranes. Many coated vesicles are attached to the surface and the invaginating whorls. It is concluded that vesicles are discharged by exocytosis and fusion of their membrane with the external surface, and that at room temperature, membrane is reinternalized by coated vesicles and formed into irregular compartments. In completion of the cycle, these compartments disappear, and the vesicle population recovers over an hour or two of rest. When the Mauthner fibers are stimulated at low rates, the p.s.p.'s in the giant fibers are large and suprathreshold. Minature p.s.p.'s are generated spontaneously or can be evoked by subthreshold depolarization or tetanic stimulation of the Mauthner fiber. Stimulation of the Mauthner fibers at gradually increasing frequencies depresses p.s.p. amplitude to or below the level of miniature p.s.p.'s, but no failures are observed. Small p.s.p.'s without failures suggest that the quantum number remains high but that quantal size is greatly reduced, either by partial filling, as is supported by the morphological observation of vesicle depletion, or by desensitization. When stimulation is stopped, recovery of p.s.p. amplitude occurs in 1 or 2 seconds, but if tetanic stimulation is resumed immediately, p.s.p. amplitude decreases again and much more rapidly than in the initial rundown. This result suggests that depression of p.s.p. amplitude is not due to desensitization and leaves partial filling as the most likely explanation of small quanta. Calculated quantal size following a tetanus recovers in 200-500 ms, which probably largely reflects the time for filling since enough vesicles can be supplied to prevent failures with much shorter intervals between stimuli. Because quantal size appears to decrease gradually as stimulation frequency increases, it appears that release of vesicles can interrupt filling, leading to the conclusion that filling and release sites are very close together. This conlusion is consistent with other data in the literature obtained by different techniques.", "contents": "Stimulation-induced depletion of vesicles, fatigue of transmission and recovery processes at a vertebrate central synapse. The Mauthner fiber giant fiber synapses of the hatchetfish are chemically transmitting axo-axionic synapses in the medulla. Tetanic stimulation at room temperature depletes the presynaptic Mauthner terminal of vesicles and leads to the appearance of large numbers of irregular membraneous compartments in the terminal. Stimulation during cooling to 12 degrees C depletes the terminal of vesicles and greatly increases the external surface, which forms large whorls of invaginating double membranes. Many coated vesicles are attached to the surface and the invaginating whorls. It is concluded that vesicles are discharged by exocytosis and fusion of their membrane with the external surface, and that at room temperature, membrane is reinternalized by coated vesicles and formed into irregular compartments. In completion of the cycle, these compartments disappear, and the vesicle population recovers over an hour or two of rest. When the Mauthner fibers are stimulated at low rates, the p.s.p.'s in the giant fibers are large and suprathreshold. Minature p.s.p.'s are generated spontaneously or can be evoked by subthreshold depolarization or tetanic stimulation of the Mauthner fiber. Stimulation of the Mauthner fibers at gradually increasing frequencies depresses p.s.p. amplitude to or below the level of miniature p.s.p.'s, but no failures are observed. Small p.s.p.'s without failures suggest that the quantum number remains high but that quantal size is greatly reduced, either by partial filling, as is supported by the morphological observation of vesicle depletion, or by desensitization. When stimulation is stopped, recovery of p.s.p. amplitude occurs in 1 or 2 seconds, but if tetanic stimulation is resumed immediately, p.s.p. amplitude decreases again and much more rapidly than in the initial rundown. This result suggests that depression of p.s.p. amplitude is not due to desensitization and leaves partial filling as the most likely explanation of small quanta. Calculated quantal size following a tetanus recovers in 200-500 ms, which probably largely reflects the time for filling since enough vesicles can be supplied to prevent failures with much shorter intervals between stimuli. Because quantal size appears to decrease gradually as stimulation frequency increases, it appears that release of vesicles can interrupt filling, leading to the conclusion that filling and release sites are very close together. This conlusion is consistent with other data in the literature obtained by different techniques."} {"id": "PMID:181198", "title": "Synaptic organization and acetylcholine sensitivity of multiply innervated autonomic ganglion cells.", "content": "The principal cells of the mudpuppy cardiac ganglion receive synapses from three sources: vagal axons, interneurons and axon collaterals from other principal cells. The simplicity of the structural organization and the visual clarity in the living preparation provide favorable conditions for examining the function of these synapses and how different classes of synapses on the same cell influence its function. We have studied the sensitivity of the principal cells to iontophoretically applied acetylcholine--the transmitter at synapses made by the vagal axons and by postganglionic axon collaterals from other principal cells. In normal ganglia, the ACh sensitivity on the cell surface is highest at the region of synapses. Partial denervation, produced by severing the vagus nerves, results in an increased ACh sensitivity in nonsynaptic areas but does not appear to affect synaptic transmission at the remaining synapses.", "contents": "Synaptic organization and acetylcholine sensitivity of multiply innervated autonomic ganglion cells. The principal cells of the mudpuppy cardiac ganglion receive synapses from three sources: vagal axons, interneurons and axon collaterals from other principal cells. The simplicity of the structural organization and the visual clarity in the living preparation provide favorable conditions for examining the function of these synapses and how different classes of synapses on the same cell influence its function. We have studied the sensitivity of the principal cells to iontophoretically applied acetylcholine--the transmitter at synapses made by the vagal axons and by postganglionic axon collaterals from other principal cells. In normal ganglia, the ACh sensitivity on the cell surface is highest at the region of synapses. Partial denervation, produced by severing the vagus nerves, results in an increased ACh sensitivity in nonsynaptic areas but does not appear to affect synaptic transmission at the remaining synapses."} {"id": "PMID:181200", "title": "The structure and permeability of isolated hepatocyte gap junctions.", "content": "The ultrastructure of the gap junction may be visualized in both in situ and isolated preparations by using a variety of electron microscope techniques. The junction is composed of a lattice of subunits, called connexons, which show variable degrees of packing into a hexagonal lattice depending on a variety of poorly understood conditions. In general, it appears that more uncoupled and \"dead\" the junction, the more regular and condensed the hexagonal lattice becomes. It is not yet known whether these are \"postmortem\" changes or physiologically active and reversible changes involved in regulation of junctional permeability. Using a variety of techniques, it can be seen that the connexon extends completely across the junctional membranes, from the cytoplasmic surface of one cell to the cytoplasmic surface of the other, spanning the 2-nm \"gap\" between the apposed junctional membranes. Thus it is possible to implicate the connexon as a permeability channel from cytoplasm to cytoplasm, although the hydrophilic pore through the center of the connexon has not yet been demonstrated to span the full junction thickness. X-ray diffraction experiments support these conclusions, and the excellent correlation between the electron microscope and X-ray diffraction data lends great confidence to the interpretations of gap junction structure presented thus far. These data are summarized in the drawing in Figure 17. This is a scale drawing of two connexons, each of which is imagined to be composed of a dimer of hexamers. It must be emphasized that as yet there is no direct evidence for a sixfold symmetry within the connexon. Of special interest now are the types of protein-protein interactions that hold the two halves of the connexon together across the 2-nm gap and the lateral interactions between the connexons at the level of the lipid bilayers.", "contents": "The structure and permeability of isolated hepatocyte gap junctions. The ultrastructure of the gap junction may be visualized in both in situ and isolated preparations by using a variety of electron microscope techniques. The junction is composed of a lattice of subunits, called connexons, which show variable degrees of packing into a hexagonal lattice depending on a variety of poorly understood conditions. In general, it appears that more uncoupled and \"dead\" the junction, the more regular and condensed the hexagonal lattice becomes. It is not yet known whether these are \"postmortem\" changes or physiologically active and reversible changes involved in regulation of junctional permeability. Using a variety of techniques, it can be seen that the connexon extends completely across the junctional membranes, from the cytoplasmic surface of one cell to the cytoplasmic surface of the other, spanning the 2-nm \"gap\" between the apposed junctional membranes. Thus it is possible to implicate the connexon as a permeability channel from cytoplasm to cytoplasm, although the hydrophilic pore through the center of the connexon has not yet been demonstrated to span the full junction thickness. X-ray diffraction experiments support these conclusions, and the excellent correlation between the electron microscope and X-ray diffraction data lends great confidence to the interpretations of gap junction structure presented thus far. These data are summarized in the drawing in Figure 17. This is a scale drawing of two connexons, each of which is imagined to be composed of a dimer of hexamers. It must be emphasized that as yet there is no direct evidence for a sixfold symmetry within the connexon. Of special interest now are the types of protein-protein interactions that hold the two halves of the connexon together across the 2-nm gap and the lateral interactions between the connexons at the level of the lipid bilayers."} {"id": "PMID:181202", "title": "Modification and regeneration of synaptic connections in cultured leech ganglia.", "content": "Segmental ganglia of the central nervous system of the leech were maintained in culture medium outside the animal for several weeks in order to study the properties of synapses and regeneration by identified sensory and motor nerve cells. A variety of preparations were used, including single ganglia, chains of ganglia and ganglia connected to the areas of skin and muscle that they normally innervate in the animal. (1) For up to 10 weeks after removal from the animal, resting and action potentials recorded from sensory and motor neurons resembled those seen in normal ganglia. The same individual cell in a cultured ganglion could be recorded from with intracellular electrodes on a second occasion after an interval of a few days. (2) Sensory cells, identified as touch, pressure or nociceptive according to their morphology and electrical properties, continued to respond selectively to stimuli of the appropriate modality applied to their receptive fields in the skin; action potentials in motor cells caused contractions in the appropriate muscles. Culture of ganglia for more than 3 weeks caused the disappearance of synaptic potentials and a loss of transparency in ganglia. (3) Certain chemically mediated synaptic interactions between sensory and motor nerve cells became markedly changed in cultured ganglia. These changes appeared over the first 3 weeks and consisted of abnormally large excitatory and inhibitory synaptic potentials. The changes in synaptic transmission observed in culture were in many respects similar to those occurring in ganglia maintained within an animal after lesions have been made in the nervous system (Jansen et al. 1974). (4) The morphological appearances of sensory cells were compared in cultured and normal ganglia after injection of horseradish peroxidase. In cultured ganglia, the branching pattern appeared normal, but varicosities became more conspicuous. (5) When connectives linking cultured ganglia were crushed or cut, regeneration occurred. By 7 days, impulses propagated through the regenerated fibers and evoked synaptic potentials on cells within the next ganglion. The course taken by regenerating axons was observed in cells injected with horseradish peroxidase. The results again resembled those seen in animals with similar lesions. (6) The cultured ganglia provide preparations in which it is possible to analyze the mechanisms that underlie long-term changes similar to those seen in the leech central nervous system in situ.", "contents": "Modification and regeneration of synaptic connections in cultured leech ganglia. Segmental ganglia of the central nervous system of the leech were maintained in culture medium outside the animal for several weeks in order to study the properties of synapses and regeneration by identified sensory and motor nerve cells. A variety of preparations were used, including single ganglia, chains of ganglia and ganglia connected to the areas of skin and muscle that they normally innervate in the animal. (1) For up to 10 weeks after removal from the animal, resting and action potentials recorded from sensory and motor neurons resembled those seen in normal ganglia. The same individual cell in a cultured ganglion could be recorded from with intracellular electrodes on a second occasion after an interval of a few days. (2) Sensory cells, identified as touch, pressure or nociceptive according to their morphology and electrical properties, continued to respond selectively to stimuli of the appropriate modality applied to their receptive fields in the skin; action potentials in motor cells caused contractions in the appropriate muscles. Culture of ganglia for more than 3 weeks caused the disappearance of synaptic potentials and a loss of transparency in ganglia. (3) Certain chemically mediated synaptic interactions between sensory and motor nerve cells became markedly changed in cultured ganglia. These changes appeared over the first 3 weeks and consisted of abnormally large excitatory and inhibitory synaptic potentials. The changes in synaptic transmission observed in culture were in many respects similar to those occurring in ganglia maintained within an animal after lesions have been made in the nervous system (Jansen et al. 1974). (4) The morphological appearances of sensory cells were compared in cultured and normal ganglia after injection of horseradish peroxidase. In cultured ganglia, the branching pattern appeared normal, but varicosities became more conspicuous. (5) When connectives linking cultured ganglia were crushed or cut, regeneration occurred. By 7 days, impulses propagated through the regenerated fibers and evoked synaptic potentials on cells within the next ganglion. The course taken by regenerating axons was observed in cells injected with horseradish peroxidase. The results again resembled those seen in animals with similar lesions. (6) The cultured ganglia provide preparations in which it is possible to analyze the mechanisms that underlie long-term changes similar to those seen in the leech central nervous system in situ."} {"id": "PMID:181203", "title": "Transmission of signals from photoreceptors to ganglion cells in the eye of the turtle.", "content": "Synaptic transfer between receptors and ganglion cells was studied in the retina of the turtle. In the normal operation of this pathway, signals are relayed across two or more chemical synapses. Previous work indicates that the receptors give graded hyperpolarization to light, and that the bipolar cells also respond with graded potential changes; the ganglion cells give impulses. Injection of weak electrical currents into a single receptor provides an alternative means of activating the pathway. We have used this technique to examine (1) the role of the receptors' hyperpolarization in signal transmission and (2) the sensitivity and temporal properties of the pathway. The response of a ganglion cell evoked by light on the retina can be duplicated by electrically hyperpolarizing a receptor and antagonized by electrical depolarization. This indicates that the hyperpolarization is responsible for regulating the flow of information from the receptors to the second-order retinal cells. The sensitivity of the synaptic path from cones to ganglion cells, determined from electrical stimulation of single receptors, was found to be sufficient to permit detection of about 100 photoisomerizations. Using the same technique, the kinetics of transfer were studied and found to exhibit a delay or integrating process and also a slow differentiation that blocks steady-state transmission. For the path from red-sensitive cones to ganglion cells, the apparent time constant of the delay process was of the order of 75 ms and that of the differentiation, about 100 ms. In the path from rods to ganglion cells, the differentiation was several times slower.", "contents": "Transmission of signals from photoreceptors to ganglion cells in the eye of the turtle. Synaptic transfer between receptors and ganglion cells was studied in the retina of the turtle. In the normal operation of this pathway, signals are relayed across two or more chemical synapses. Previous work indicates that the receptors give graded hyperpolarization to light, and that the bipolar cells also respond with graded potential changes; the ganglion cells give impulses. Injection of weak electrical currents into a single receptor provides an alternative means of activating the pathway. We have used this technique to examine (1) the role of the receptors' hyperpolarization in signal transmission and (2) the sensitivity and temporal properties of the pathway. The response of a ganglion cell evoked by light on the retina can be duplicated by electrically hyperpolarizing a receptor and antagonized by electrical depolarization. This indicates that the hyperpolarization is responsible for regulating the flow of information from the receptors to the second-order retinal cells. The sensitivity of the synaptic path from cones to ganglion cells, determined from electrical stimulation of single receptors, was found to be sufficient to permit detection of about 100 photoisomerizations. Using the same technique, the kinetics of transfer were studied and found to exhibit a delay or integrating process and also a slow differentiation that blocks steady-state transmission. For the path from red-sensitive cones to ganglion cells, the apparent time constant of the delay process was of the order of 75 ms and that of the differentiation, about 100 ms. In the path from rods to ganglion cells, the differentiation was several times slower."} {"id": "PMID:181212", "title": "Reappraisal of the role of the diabetic state in coronary artery disease.", "content": "Clinical and coronary arteriographic findings were evaluated in patients with angina pectoris who were considered not to have diabetes mellitus or to have chemical or clinical diabetes. Each of the three groups consisted of 100 consecutive referred patients. Neither the age of the patients nor duration of symptoms differed significantly among the groups. Hypertension, gout, and peripheral vascular disease were more frequent in the patients with clinical diabetes. There was no difference in serum cholesterol concentration among the groups, but plasma triglyceride levels and the frequency of type 4 hyperlipoproteinemia were significantly higher (p less than 0.01) in the chemical and clinical diabetic groups than in the nondiabetic patients. Coronary arteriographic observations indicated that the severity of the coronary arterial disease was greater in both diabetic groups than in nondiabetic patients. The difference in the coronary scores among the three groups of patients interacts to some extent with the triglyceride level, since a high score in the diabetic groups was noted only in the presence of an elevated tryglyceride concentration. The results indicate that the increased severity of coronary arterial disease in diabetic patients is not attributable to age, duration of symptoms, hypertension, type -4 hyperlipoproteinemia, or apparent severity of the glucose intolerance.", "contents": "Reappraisal of the role of the diabetic state in coronary artery disease. Clinical and coronary arteriographic findings were evaluated in patients with angina pectoris who were considered not to have diabetes mellitus or to have chemical or clinical diabetes. Each of the three groups consisted of 100 consecutive referred patients. Neither the age of the patients nor duration of symptoms differed significantly among the groups. Hypertension, gout, and peripheral vascular disease were more frequent in the patients with clinical diabetes. There was no difference in serum cholesterol concentration among the groups, but plasma triglyceride levels and the frequency of type 4 hyperlipoproteinemia were significantly higher (p less than 0.01) in the chemical and clinical diabetic groups than in the nondiabetic patients. Coronary arteriographic observations indicated that the severity of the coronary arterial disease was greater in both diabetic groups than in nondiabetic patients. The difference in the coronary scores among the three groups of patients interacts to some extent with the triglyceride level, since a high score in the diabetic groups was noted only in the presence of an elevated tryglyceride concentration. The results indicate that the increased severity of coronary arterial disease in diabetic patients is not attributable to age, duration of symptoms, hypertension, type -4 hyperlipoproteinemia, or apparent severity of the glucose intolerance."} {"id": "PMID:181213", "title": "Another presentation of fibrosing alveolitis and alveolar cell carcinoma.", "content": "A 73-year-old woman had dyspnea associated with gradually increasing pulmonary collapse. Despite intensive investigation, the diagnosis was only reached at autopsy 18 months later, when histologic examination of the lungs showed changes of both fibrosing alveolitis and alveolar cell carcinoma.", "contents": "Another presentation of fibrosing alveolitis and alveolar cell carcinoma. A 73-year-old woman had dyspnea associated with gradually increasing pulmonary collapse. Despite intensive investigation, the diagnosis was only reached at autopsy 18 months later, when histologic examination of the lungs showed changes of both fibrosing alveolitis and alveolar cell carcinoma."} {"id": "PMID:181214", "title": "Onset of sarcoidosis with left ventricular failure and multisystem involvement.", "content": "A patient presented with acute left ventricular failure, then developed cranial nerve palsies, myopathy, fever and hyperuricemia. Sarcoidosis was not diagnosed until the pulmonary congestion cleared, revealing hilar adenopathy and residual mottling. Thereafter, uveitis was noted and scalene and muscle biopsies confirmed the diagnosis.", "contents": "Onset of sarcoidosis with left ventricular failure and multisystem involvement. A patient presented with acute left ventricular failure, then developed cranial nerve palsies, myopathy, fever and hyperuricemia. Sarcoidosis was not diagnosed until the pulmonary congestion cleared, revealing hilar adenopathy and residual mottling. Thereafter, uveitis was noted and scalene and muscle biopsies confirmed the diagnosis."} {"id": "PMID:181215", "title": "Characterization of a nosocomially significant, multiple drug-resistant strain of Serratia marcescens.", "content": "A multiple drug-resistant strain of Serratia marcescens (bacteriocin type 18) was isolated from three clinical patients. The isolates were found to carry a conjugally nontransferable, nonmobilizeable resistance plasmid (R-plasmid) with resistance-(r)-determinants against ten antimicrobial drugs: ampicillin, carbenicillin, chloramphenicol, gentamicin, kanamycin, neomycin, streptomycin, tobramycin, triple sulfonamides, cotrimoxazole, and--possibly--nalidixic acid, as determined with exposure to 'curing' agents (ethidium bromide, acridine orange, and sodium dodecyl sulfate) and by the high rate of spontaneous loss of r-determinants. Dyebuoyant density centrifugation allowed recovery of R-plasmid DNA that measured roughly 24 mum in contour length; after 'curing' with concomitant loss of 9 r-determinants, the contour length of the R-plasmid DNA of one isolate (No. SE 154) had decreased to roughly 15 mum, and none was detected in the sole variant of the isolate that spontaneously had lost 11 r-determinants.", "contents": "Characterization of a nosocomially significant, multiple drug-resistant strain of Serratia marcescens. A multiple drug-resistant strain of Serratia marcescens (bacteriocin type 18) was isolated from three clinical patients. The isolates were found to carry a conjugally nontransferable, nonmobilizeable resistance plasmid (R-plasmid) with resistance-(r)-determinants against ten antimicrobial drugs: ampicillin, carbenicillin, chloramphenicol, gentamicin, kanamycin, neomycin, streptomycin, tobramycin, triple sulfonamides, cotrimoxazole, and--possibly--nalidixic acid, as determined with exposure to 'curing' agents (ethidium bromide, acridine orange, and sodium dodecyl sulfate) and by the high rate of spontaneous loss of r-determinants. Dyebuoyant density centrifugation allowed recovery of R-plasmid DNA that measured roughly 24 mum in contour length; after 'curing' with concomitant loss of 9 r-determinants, the contour length of the R-plasmid DNA of one isolate (No. SE 154) had decreased to roughly 15 mum, and none was detected in the sole variant of the isolate that spontaneously had lost 11 r-determinants."} {"id": "PMID:181216", "title": "A clinical investigation of pivmecillinam. A novel beta-lactam antibiotic in the treatment of urinary tract infections.", "content": "Pivmecillinam (FL 1039) is the pivaloyloxymethyl ester of mecillinam (FL 1060) which has considerable in vitro activity against Enterobacteriaceae. 38 hospital inpatients who had proven urinary tract infections were treated with 400 mg pivmecillinam four times daily for 5-7 days. The MIC of mecillinam to the infecting organisms was determined as were the serum and urinary concentrations of the antibiotic. The patients were followed up for 4-6 weeks after the end of treatment. Three patients were lost to follow-up. Of the 35 patients who were adequately followed up, 29 (83%) were classified as cured and there were 6 failures. Reported side effects were of a minor nature.", "contents": "A clinical investigation of pivmecillinam. A novel beta-lactam antibiotic in the treatment of urinary tract infections. Pivmecillinam (FL 1039) is the pivaloyloxymethyl ester of mecillinam (FL 1060) which has considerable in vitro activity against Enterobacteriaceae. 38 hospital inpatients who had proven urinary tract infections were treated with 400 mg pivmecillinam four times daily for 5-7 days. The MIC of mecillinam to the infecting organisms was determined as were the serum and urinary concentrations of the antibiotic. The patients were followed up for 4-6 weeks after the end of treatment. Three patients were lost to follow-up. Of the 35 patients who were adequately followed up, 29 (83%) were classified as cured and there were 6 failures. Reported side effects were of a minor nature."} {"id": "PMID:181217", "title": "Infection of newborn Taiwan monkeys (Macaca cyclopis) with human adenovirus type 12 and simian virus 40.", "content": "For testing biological response of newborn Taiwan monkeys to infection of human adenovirus type 12 (Ad12) and simian virus 40 (SV40), 40 newborn Taiwan monkeys were inoculated with Ad12, Ad12, plus SV40, Ad12 supplemented with Ad12-induced hamster tumor tissue (Ad12 tumor) or control specimens (HeLa or African green monkey kidney cell lysate). Among them 26 survived including 8 newborn monkeys inoculated with control specimens. The survivors were observed for 4 years but no tumor was produced. The increase of body weight and intake of calories and protein in each test group during the first 12 wk were similar to those of corresponding control groups. Intrapulmonary inoculation of 108.2TCD50 of Ad12 with additional subcutaneous dose of Ad12 (108.8TCD50), Ad12 plus SV40 (108TCD50) or Ad12 plus Ad12 tumor killed 78% of newborn monkeys (7 of 9) in 18 days. The newborn could stand subcutaneous inoculation of SV40 (108TCD50) with 1 dose of Ad12 (108.8TCD50) or 3 doses of Ad12 (108.5, 108.5 and 108.2TCD50) at 24-hr intervals. When 108.8TCD50 or more Ad12 were inoculated, the virus could be isolated as late as 44 and 26 days from rectal and throat swab specimens respectively. The Ad12 neutralizing antibody in baby monkeys inoculated with multiple doses of Ad12 persisted, in low titer, longer than those injected with single high doses of Ad12, but anti-Ad12 T (tumor) antibody disappeared by 35 wk in both groups. Although SV40 antibody response was better than Ad12 antibody response in baby Taiwan monkeys, pre-infection of SV40 did not potentiate the production of anti-Ad12 T antibody.", "contents": "Infection of newborn Taiwan monkeys (Macaca cyclopis) with human adenovirus type 12 and simian virus 40. For testing biological response of newborn Taiwan monkeys to infection of human adenovirus type 12 (Ad12) and simian virus 40 (SV40), 40 newborn Taiwan monkeys were inoculated with Ad12, Ad12, plus SV40, Ad12 supplemented with Ad12-induced hamster tumor tissue (Ad12 tumor) or control specimens (HeLa or African green monkey kidney cell lysate). Among them 26 survived including 8 newborn monkeys inoculated with control specimens. The survivors were observed for 4 years but no tumor was produced. The increase of body weight and intake of calories and protein in each test group during the first 12 wk were similar to those of corresponding control groups. Intrapulmonary inoculation of 108.2TCD50 of Ad12 with additional subcutaneous dose of Ad12 (108.8TCD50), Ad12 plus SV40 (108TCD50) or Ad12 plus Ad12 tumor killed 78% of newborn monkeys (7 of 9) in 18 days. The newborn could stand subcutaneous inoculation of SV40 (108TCD50) with 1 dose of Ad12 (108.8TCD50) or 3 doses of Ad12 (108.5, 108.5 and 108.2TCD50) at 24-hr intervals. When 108.8TCD50 or more Ad12 were inoculated, the virus could be isolated as late as 44 and 26 days from rectal and throat swab specimens respectively. The Ad12 neutralizing antibody in baby monkeys inoculated with multiple doses of Ad12 persisted, in low titer, longer than those injected with single high doses of Ad12, but anti-Ad12 T (tumor) antibody disappeared by 35 wk in both groups. Although SV40 antibody response was better than Ad12 antibody response in baby Taiwan monkeys, pre-infection of SV40 did not potentiate the production of anti-Ad12 T antibody."} {"id": "PMID:181218", "title": "Host preference of mosquito vectors of Japanese encephalitis.", "content": "The host preference of 4 Culex mosquito species collected in Miaoli and Pingtung counties, Taiwan was studied by capillary precipitin method. Antisera to alum-precipitated sera of man, bovine, swine, rabbit, horse, dog, cat, mouse, chicken, duck, and pigeon were produced in rabbits and reacted with 758 mosquito blood meals among which reactions to one or more antisera. Culex annulus and Culex tritaeniorhynchus summorosus showed a great avidity for pig, and Culex fuscocephala for bovine. Culex pipiens fatigans was ornithophilic. None of 110 C. t. summorosus and 2.4% of 223 C. annulus had fed on man. Among 66 samples of C.p. fatigans tested 10.3% had fed on man, while none of 359 C. fuscocephala did. It seems that the latter does not act as a primary vector of Japanese encephalitis.", "contents": "Host preference of mosquito vectors of Japanese encephalitis. The host preference of 4 Culex mosquito species collected in Miaoli and Pingtung counties, Taiwan was studied by capillary precipitin method. Antisera to alum-precipitated sera of man, bovine, swine, rabbit, horse, dog, cat, mouse, chicken, duck, and pigeon were produced in rabbits and reacted with 758 mosquito blood meals among which reactions to one or more antisera. Culex annulus and Culex tritaeniorhynchus summorosus showed a great avidity for pig, and Culex fuscocephala for bovine. Culex pipiens fatigans was ornithophilic. None of 110 C. t. summorosus and 2.4% of 223 C. annulus had fed on man. Among 66 samples of C.p. fatigans tested 10.3% had fed on man, while none of 359 C. fuscocephala did. It seems that the latter does not act as a primary vector of Japanese encephalitis."} {"id": "PMID:181219", "title": "Permeability of pulmonary vascular endothelium.", "content": "Three aspects of transendothelial exchange in the lungs are considered: stretching of interendothelial junctions of pulmonary microvessels by increase in pulmonary capillary pressures; selective stretching of interendothelial junctions of bronchial venules in response to histamine, bradykinin and endotoxin; active transport of peptides across the body of the endothelial cell after enzymic action at or near the luminal surface of the endothelial cell. Stretching of interendothelial junctions between the cells lining the pulmonary capillaries was demonstrated using a variety of macromolecular tracers under controlled haemodynamic conditions. Selective leakage of bronchial venules, the systemic venules of the lungs, was shown using colloidal carbon as a tracer. Transendothelial transport of peptides across the pulmonary capillary lining involved the use of electron microscopic autoradiography after intravenous administration of radioactively-labelled lipoproteins. Different mechanisms appear to provide routes of entry into the perivascular interstitial spaces of the lungs.", "contents": "Permeability of pulmonary vascular endothelium. Three aspects of transendothelial exchange in the lungs are considered: stretching of interendothelial junctions of pulmonary microvessels by increase in pulmonary capillary pressures; selective stretching of interendothelial junctions of bronchial venules in response to histamine, bradykinin and endotoxin; active transport of peptides across the body of the endothelial cell after enzymic action at or near the luminal surface of the endothelial cell. Stretching of interendothelial junctions between the cells lining the pulmonary capillaries was demonstrated using a variety of macromolecular tracers under controlled haemodynamic conditions. Selective leakage of bronchial venules, the systemic venules of the lungs, was shown using colloidal carbon as a tracer. Transendothelial transport of peptides across the pulmonary capillary lining involved the use of electron microscopic autoradiography after intravenous administration of radioactively-labelled lipoproteins. Different mechanisms appear to provide routes of entry into the perivascular interstitial spaces of the lungs."} {"id": "PMID:181220", "title": "Ultrastructural basis for alveolar-capillary permeability to protein.", "content": "The intravenous injection into mice of small volumes (less than 0.1 ml) of peroxidatic enzymes of molecular weight of 40 000 daltons or greater results in little if any penetration of these probe molecules into endothelial junctions. The injection of cytochrome c (12 000 daltons), on the other hand, results in the localization of this tracer in some but not all endothelial junctions. When horseradish peroxidase (EC 1.11.1.7) is injected in a large volume of saline (0.5 ml), reaction product is present in endothelial junctions and basement membrane, but is prevented from entering the alveolar space by zonulae occludentes between epithelial cells. These experiments indicate that although endothelial junctions, under physiological conditions, are largely impermeable to molecules the size of horseradish peroxidase, and presumably most serum proteins, they are labile and susceptible to stretching if intravascular pressure is increased. Freeze-fracture studies show that pulmonary capillary endothelial junctions are composed of one or at the most two strands which show areas of discontinuity. Epithelial junctions, by contrast, are composed of a continuous, complex network of anastomosing fibres. These observations confirm physiological experiments which indicate that it is the pulmonary epithelium rather than the endothelium which determines the permeability properties of the alveolar-capillary membrane to lipid-insoluble molecules. Bidirectional pinocytic transport is an additional mechanism whereby lipid-insoluble molecules are transported across both endothelial and epithelial layers. The relative contribution of this transport mechanism to the total amount transported remains to be established.", "contents": "Ultrastructural basis for alveolar-capillary permeability to protein. The intravenous injection into mice of small volumes (less than 0.1 ml) of peroxidatic enzymes of molecular weight of 40 000 daltons or greater results in little if any penetration of these probe molecules into endothelial junctions. The injection of cytochrome c (12 000 daltons), on the other hand, results in the localization of this tracer in some but not all endothelial junctions. When horseradish peroxidase (EC 1.11.1.7) is injected in a large volume of saline (0.5 ml), reaction product is present in endothelial junctions and basement membrane, but is prevented from entering the alveolar space by zonulae occludentes between epithelial cells. These experiments indicate that although endothelial junctions, under physiological conditions, are largely impermeable to molecules the size of horseradish peroxidase, and presumably most serum proteins, they are labile and susceptible to stretching if intravascular pressure is increased. Freeze-fracture studies show that pulmonary capillary endothelial junctions are composed of one or at the most two strands which show areas of discontinuity. Epithelial junctions, by contrast, are composed of a continuous, complex network of anastomosing fibres. These observations confirm physiological experiments which indicate that it is the pulmonary epithelium rather than the endothelium which determines the permeability properties of the alveolar-capillary membrane to lipid-insoluble molecules. Bidirectional pinocytic transport is an additional mechanism whereby lipid-insoluble molecules are transported across both endothelial and epithelial layers. The relative contribution of this transport mechanism to the total amount transported remains to be established."} {"id": "PMID:181221", "title": "The control of insulin release by sugars.", "content": "The interaction of glucose, the major physiological regulator of insulin secretion, with the beta-cell involves the recognition of glucose as a signal, the transduction of this recognition into an intracellular event and the coupling of the event to the exocytotic discharge of insulin from secretory granules. The following aspects of this system are discussed: (1) the mechanism of insulin release; (2) the evidence implicating Ca2+ and cyclic AMP as coupling factors; (3) the main characteristics of glucose-stimulated insulin release; (4) gluco-receptor models and the evidence for them; (5) possible mechanisms for transduction of the response to glucose; (6) the extent to which the systems of the secretory response to sugars may also be involved in the control of proinsulin biosynthesis; (7) whether starvation induces specific changes in the glucoreceptor system.", "contents": "The control of insulin release by sugars. The interaction of glucose, the major physiological regulator of insulin secretion, with the beta-cell involves the recognition of glucose as a signal, the transduction of this recognition into an intracellular event and the coupling of the event to the exocytotic discharge of insulin from secretory granules. The following aspects of this system are discussed: (1) the mechanism of insulin release; (2) the evidence implicating Ca2+ and cyclic AMP as coupling factors; (3) the main characteristics of glucose-stimulated insulin release; (4) gluco-receptor models and the evidence for them; (5) possible mechanisms for transduction of the response to glucose; (6) the extent to which the systems of the secretory response to sugars may also be involved in the control of proinsulin biosynthesis; (7) whether starvation induces specific changes in the glucoreceptor system."} {"id": "PMID:181222", "title": "The mode of action of adenosine 3':5'-cyclic phosphate in the regulation of insulin secretion.", "content": "Changes in the pancreatic beta-cell concentrations of adenosine 3':5'-cyclic phosphate (cyclic AMP) may lead to changes in rates of insulin release, although little is known of the exact mechanism by which this nucleotide may influence the secretory process. Previous studies indicated that in the beta-cell, as in other mammalian cell types, the effects of cyclic AMP may be exerted by the activation of a cyclic AMP-dependent protein kinase, and we have attempted to identify possible substrates for this enzyme in beta-cells. Cyclic AMP stimulated the phosphorylation of specific non-nuclear protein substrates; this effect was observed both in intact cells preincubated with sodium [32P]phosphate to label intracellular ATP and in broken cell preparations incubated with [gamma-32P]ATP. The substrates for protein kinase in islets are unknown but as in other tissues might include microtubular protein and specific proteins of the granule and plasma membranes. In separate experiments cyclic AMP stimulated the efflux of calcium from an organelle-bound (probably mitochondrial) pool, and this may result in rapid changes of intracellular calcium distribution in the beta-cell; these might in turn play an important role in the regulation of secretion. These results suggest that cyclic AMP may directly affect cytosolic calcium concentrations in the beta-cell, as well as promoting the phosphorylation and activity of other components which may be necessary for the maintenance of adequate secretory responses.", "contents": "The mode of action of adenosine 3':5'-cyclic phosphate in the regulation of insulin secretion. Changes in the pancreatic beta-cell concentrations of adenosine 3':5'-cyclic phosphate (cyclic AMP) may lead to changes in rates of insulin release, although little is known of the exact mechanism by which this nucleotide may influence the secretory process. Previous studies indicated that in the beta-cell, as in other mammalian cell types, the effects of cyclic AMP may be exerted by the activation of a cyclic AMP-dependent protein kinase, and we have attempted to identify possible substrates for this enzyme in beta-cells. Cyclic AMP stimulated the phosphorylation of specific non-nuclear protein substrates; this effect was observed both in intact cells preincubated with sodium [32P]phosphate to label intracellular ATP and in broken cell preparations incubated with [gamma-32P]ATP. The substrates for protein kinase in islets are unknown but as in other tissues might include microtubular protein and specific proteins of the granule and plasma membranes. In separate experiments cyclic AMP stimulated the efflux of calcium from an organelle-bound (probably mitochondrial) pool, and this may result in rapid changes of intracellular calcium distribution in the beta-cell; these might in turn play an important role in the regulation of secretion. These results suggest that cyclic AMP may directly affect cytosolic calcium concentrations in the beta-cell, as well as promoting the phosphorylation and activity of other components which may be necessary for the maintenance of adequate secretory responses."} {"id": "PMID:181223", "title": "Multiple forms of corticotropin (adrenocorticotropic hormone, ACTH) and their significance.", "content": "Big corticotropin (adrenocroticotropic hormone, ACTH), an immunoreactive form of ACTH with low biological activity and which elutes in the void volume on Sephadex G-50 gel filtration, is found in plasma and extracts of human pituitary and tumour. Controlled tryptic digestion of big ACTH releases a product with full corticotropic activity which is indistinguishable from the (1-39) ACTH with respect to size, charge and susceptibility to tryptic digestion. Immunoreactive ACTH, predominantly in the big form, is found in virtually all tissue extracts of carcinoma primary to or metastatic from the lung, but not of carcinoma metastatic to the lung, and even in precancerous lung lesions. The absence of clinical Cushing syndrome in patients with carcinoma of the lung and moderate elevation of plasma concentrations of ACTH is due to the low biological activity of big ACTH. Prolonged survival (for more than two years) of patients with lung carcinoma has been observed only in those whose plasma ACTH is low before therapy or after resection of the lung tumour. Rabbit, rat and mouse pituitaries contain an intermediate sized ACTH but the usual 1-39 peptide predominates in the pituitaries of monkey, sheep, dog, cat and guinea pig, as well as man. The hormonal form of ACTH appears to be an important factor regulating the cortisol/corticosterone ratio in mammalian adrenal corticoid secretion because administration of porcine ACTH to rabbits alters the adrenal secretory pattern so as to decrease corticosterone production and increase cortisol production.", "contents": "Multiple forms of corticotropin (adrenocorticotropic hormone, ACTH) and their significance. Big corticotropin (adrenocroticotropic hormone, ACTH), an immunoreactive form of ACTH with low biological activity and which elutes in the void volume on Sephadex G-50 gel filtration, is found in plasma and extracts of human pituitary and tumour. Controlled tryptic digestion of big ACTH releases a product with full corticotropic activity which is indistinguishable from the (1-39) ACTH with respect to size, charge and susceptibility to tryptic digestion. Immunoreactive ACTH, predominantly in the big form, is found in virtually all tissue extracts of carcinoma primary to or metastatic from the lung, but not of carcinoma metastatic to the lung, and even in precancerous lung lesions. The absence of clinical Cushing syndrome in patients with carcinoma of the lung and moderate elevation of plasma concentrations of ACTH is due to the low biological activity of big ACTH. Prolonged survival (for more than two years) of patients with lung carcinoma has been observed only in those whose plasma ACTH is low before therapy or after resection of the lung tumour. Rabbit, rat and mouse pituitaries contain an intermediate sized ACTH but the usual 1-39 peptide predominates in the pituitaries of monkey, sheep, dog, cat and guinea pig, as well as man. The hormonal form of ACTH appears to be an important factor regulating the cortisol/corticosterone ratio in mammalian adrenal corticoid secretion because administration of porcine ACTH to rabbits alters the adrenal secretory pattern so as to decrease corticosterone production and increase cortisol production."} {"id": "PMID:181224", "title": "Membrane topology as revealed by the binding of macromolecules.", "content": "Binding sites for specific molecules at the cell surface can be localized with the electron microscope in thin-section, freeze-etch and shadow-casting preparations. The receptors tested were binding sites to concanavalin A (Con A) labelled with haemocyanin and binding sites to insulin labelled with ferritin. Con A-binding sites were localized in endocrine cells of the pancreas and insulin-binding sites in isolated liver plasma membranes. The relevance of the topographical distribution of the binding sites to cell membrane organization is discussed.", "contents": "Membrane topology as revealed by the binding of macromolecules. Binding sites for specific molecules at the cell surface can be localized with the electron microscope in thin-section, freeze-etch and shadow-casting preparations. The receptors tested were binding sites to concanavalin A (Con A) labelled with haemocyanin and binding sites to insulin labelled with ferritin. Con A-binding sites were localized in endocrine cells of the pancreas and insulin-binding sites in isolated liver plasma membranes. The relevance of the topographical distribution of the binding sites to cell membrane organization is discussed."} {"id": "PMID:181225", "title": "Protein phosphorylation and hormone action.", "content": "Although the scheme hormone leads to raised cyclic AMP levels leads to activated protein kinase leads to phosphorylated protein leads to physiological response may represent an outline for the action of several hormones, in the best understood example, namely regulation of glucogen metabolism in mammalian muscle, the picture is more complex. Modification of phosphorylase kinase by cyclic AMP-dependent protein kinase, after stimulation by adrenaline, leads to phosphorylation of the enzyme at two sites. Activation is associated exclusively with the phosphorylation of the primary site, but the secondary phosphorylation indirectly antagonizes the primary phosphorylation in that it is necessary to render the primary site susceptible to dephosphorylation. The recent separation of two distinct phosphorylase kinase phosphatases specific for the two sites shows that reversal of the hormonal stimulation is controlled by the relative activities of two enzymes with opposing functions. Glycogen synthetase, which is phosphorylated and inactivated by cyclic AMP-dependent protein kinase, is also under the control of insulin. Although insulin appears to stimulate glycogen synthetase by reversal of the inactivation catalysed by the cyclic AMP-dependent protein kinase, tissue cyclic AMP concentrations do not alter. The recent identification of a second glycogen synthetase kinase, unaffected by cyclic AMP, therefore raises the possibility that insulin action may also be mediated through phosphorylation-dephosphorylation mechanisms, which antagonize those mediated through cyclic AMP-dependent protein kinase.", "contents": "Protein phosphorylation and hormone action. Although the scheme hormone leads to raised cyclic AMP levels leads to activated protein kinase leads to phosphorylated protein leads to physiological response may represent an outline for the action of several hormones, in the best understood example, namely regulation of glucogen metabolism in mammalian muscle, the picture is more complex. Modification of phosphorylase kinase by cyclic AMP-dependent protein kinase, after stimulation by adrenaline, leads to phosphorylation of the enzyme at two sites. Activation is associated exclusively with the phosphorylation of the primary site, but the secondary phosphorylation indirectly antagonizes the primary phosphorylation in that it is necessary to render the primary site susceptible to dephosphorylation. The recent separation of two distinct phosphorylase kinase phosphatases specific for the two sites shows that reversal of the hormonal stimulation is controlled by the relative activities of two enzymes with opposing functions. Glycogen synthetase, which is phosphorylated and inactivated by cyclic AMP-dependent protein kinase, is also under the control of insulin. Although insulin appears to stimulate glycogen synthetase by reversal of the inactivation catalysed by the cyclic AMP-dependent protein kinase, tissue cyclic AMP concentrations do not alter. The recent identification of a second glycogen synthetase kinase, unaffected by cyclic AMP, therefore raises the possibility that insulin action may also be mediated through phosphorylation-dephosphorylation mechanisms, which antagonize those mediated through cyclic AMP-dependent protein kinase."} {"id": "PMID:181226", "title": "Growth-promoting actions of peptide hormones.", "content": "In common with other growth-promoting hormones, peptide hormones evoke multiple biochemical responses in their target tissues. These can be divided into two groups: (a) rapid effects involving permeability properties of the target cell to amino acids, sugars and ions or changes in key intracellular metabolites like cyclic nucleotides; (b) slow responses based on the stimulation of RNA and protein synthesis. The impossibility of explaining all the late events as the results of early changes raises the possibility that more than one species of hormone receptor exists. It is proposed that the final expression of growth and maturation results from the cooperative interaction of rapid and slow responses of the target cell to the hormone.", "contents": "Growth-promoting actions of peptide hormones. In common with other growth-promoting hormones, peptide hormones evoke multiple biochemical responses in their target tissues. These can be divided into two groups: (a) rapid effects involving permeability properties of the target cell to amino acids, sugars and ions or changes in key intracellular metabolites like cyclic nucleotides; (b) slow responses based on the stimulation of RNA and protein synthesis. The impossibility of explaining all the late events as the results of early changes raises the possibility that more than one species of hormone receptor exists. It is proposed that the final expression of growth and maturation results from the cooperative interaction of rapid and slow responses of the target cell to the hormone."} {"id": "PMID:181227", "title": "Prohormones of beta-melanotropin (beta-melanocyte-stimulating hormone, beta-MSH) and corticotropin (adrenocorticotropic hormone, ACTH): structure and activation.", "content": "It is proposed that all peptide hormones and releasing factors are biosynthesized in the form of precursor molecules which are biologically inactive. Enzymic activation may take place by hydrolytic cleavage to release a terminal COOH group or by transmidation to form a COOH-terminal amide. Studies with pituitary prohormones and hormones are providing data that support this hypothesis. Evidence has been obtained that the 91 residue beta-lipotropin (beta-LPH) is the prohormone of beta-melanotropin (beta-MSH). The specificity of the pituitary enzymes involved in release of the hormone was demonstrated by the isolation of five constituent fragments of LPH, which were obtained in homogeneous form from the pituitary gland of the pig. The enzymes have specificities similar to trypsin and carboxypeptidase B; carboxypeptidase A and aminopeptidase activities do not appear to be involved. Mild digestion of beta-LPH by trypsin in vitro has confirmed the susceptibility of the peptide bond on the carboxy side of the paired basic residues at positions 59 and 60, adjacent to the COOH-terminus of beta-MSH, and tryptic digestion of a model peptide demonstrated the same specificity. The paired basic residues at positions 39 and 40 adjacent to the NH2-terminus of beta-MSH were more resistant to tryptic attack, both in LPH and in a model peptide. In the gland it is apparent that LPH is cleaved on the carboxy side of the paired lysyl residues at positions 39 and 40, whereas in the synthetic peptide cleavage takes place in between these residues. The activating enzyme may differ from trypsin; alternatively, explanation may be found in the conformation of the prohormone. Prediction of secondary indicates that both pairs of basic residues lie adjacent to beta-bends on the surface of the molecule and occupy sites accessible to enzymic attack. It seems likely that alpha-MSH and corticotropin (ACTH) share a common pro hormone. The release of ACTH could involve cleavage of a -Gly-Ser- bond in the prohormone to expose the NH2-terminus of the hormone. With alpha-MSH, a concerted acetylation and cleavage may take place to form the N-acetylserine residue; the COOH-terminus may be released as an amide by direct transamidation of a -Val-Gly- bond in the prohormone. Release of either hormone would be accompanied by the release of contiguous fragments of the prohormone. We have isolated two novel polypeptides from pig pituitary in substantial quantity and have determined the primary structures. They may represent fragments of a prohormone to alpha-MSH or ACTH.", "contents": "Prohormones of beta-melanotropin (beta-melanocyte-stimulating hormone, beta-MSH) and corticotropin (adrenocorticotropic hormone, ACTH): structure and activation. It is proposed that all peptide hormones and releasing factors are biosynthesized in the form of precursor molecules which are biologically inactive. Enzymic activation may take place by hydrolytic cleavage to release a terminal COOH group or by transmidation to form a COOH-terminal amide. Studies with pituitary prohormones and hormones are providing data that support this hypothesis. Evidence has been obtained that the 91 residue beta-lipotropin (beta-LPH) is the prohormone of beta-melanotropin (beta-MSH). The specificity of the pituitary enzymes involved in release of the hormone was demonstrated by the isolation of five constituent fragments of LPH, which were obtained in homogeneous form from the pituitary gland of the pig. The enzymes have specificities similar to trypsin and carboxypeptidase B; carboxypeptidase A and aminopeptidase activities do not appear to be involved. Mild digestion of beta-LPH by trypsin in vitro has confirmed the susceptibility of the peptide bond on the carboxy side of the paired basic residues at positions 59 and 60, adjacent to the COOH-terminus of beta-MSH, and tryptic digestion of a model peptide demonstrated the same specificity. The paired basic residues at positions 39 and 40 adjacent to the NH2-terminus of beta-MSH were more resistant to tryptic attack, both in LPH and in a model peptide. In the gland it is apparent that LPH is cleaved on the carboxy side of the paired lysyl residues at positions 39 and 40, whereas in the synthetic peptide cleavage takes place in between these residues. The activating enzyme may differ from trypsin; alternatively, explanation may be found in the conformation of the prohormone. Prediction of secondary indicates that both pairs of basic residues lie adjacent to beta-bends on the surface of the molecule and occupy sites accessible to enzymic attack. It seems likely that alpha-MSH and corticotropin (ACTH) share a common pro hormone. The release of ACTH could involve cleavage of a -Gly-Ser- bond in the prohormone to expose the NH2-terminus of the hormone. With alpha-MSH, a concerted acetylation and cleavage may take place to form the N-acetylserine residue; the COOH-terminus may be released as an amide by direct transamidation of a -Val-Gly- bond in the prohormone. Release of either hormone would be accompanied by the release of contiguous fragments of the prohormone. We have isolated two novel polypeptides from pig pituitary in substantial quantity and have determined the primary structures. They may represent fragments of a prohormone to alpha-MSH or ACTH."} {"id": "PMID:181236", "title": "On the mechanism of inhibition by iodine of the thyroid adenylate cyclase response to thyrotropic hormone.", "content": "Rats maintained on a low-iodine diet were hypophysectomized, and their diet was than enriched with iodide. Cyclic AMP (cAMP) concentrations achieved in their thyroids following in vitro TSH stimulation were significantly lower than those in the thyroids of control animals that did not receive dietary iodide enrichment. The addition of 0.1% methimazole (MMI) or 1% KC1O4 to the diet abolished this inhibitory effect of iodide. The administration of triiodothyronine in the died did not reproduce the inhibitory effect of iodide. The effect of iodide in vitro on the thyroid cAMP response to TSH was then investigated using paired thyroid lobes obtained from intact rats fed a low-iodine diet. During a 15-min incubation period, concentrations of iodide up to 10(-3)M, together with TSH (125 mU/ml), did not affect the thyroid cAMP response to TSH. In contrast, the preincubation of the lobes in 5 X 10(-5)M Nal for 2 h preceding a final 15-min incubation in medium containing TSH alone resulted in final cAMP concentrations significantly lower than those in paired lobes not exposed to iodide. Basal cAMP concentrations in thyroids not subjected to TSH stimulation were unaffected by preincubation in iodide. The inclusion of TSH during the preincubation period augmented the inhibitory effect of iodide on the final thyroid cAMP concentration achieved. The inclusion of MMI together with iodide during the preincubation period abolished the inhibitory effect of iodide on the final cAMP concentration achieved by TSH stimulation. Direct measurement of newly formed organic iodine in vitro demonstrated it to be inversely proportional to the final cAMP concentration achieved by TSH stimulation. The preincubation of thyroid lobes in iodide was without effect on the subsequent stimulation of cAMP by PGE1, or on the stimulation by F- of adenylate cyclase activity in the thyroid homogenate. The data support the concept of an as yet unknown organic form of iodine that limits thyroid adenylate cyclase responsiveness to TSH stimulation. This may, in part, explain the diverse, and generally inhibitory, actions of iodide on thyroid function.", "contents": "On the mechanism of inhibition by iodine of the thyroid adenylate cyclase response to thyrotropic hormone. Rats maintained on a low-iodine diet were hypophysectomized, and their diet was than enriched with iodide. Cyclic AMP (cAMP) concentrations achieved in their thyroids following in vitro TSH stimulation were significantly lower than those in the thyroids of control animals that did not receive dietary iodide enrichment. The addition of 0.1% methimazole (MMI) or 1% KC1O4 to the diet abolished this inhibitory effect of iodide. The administration of triiodothyronine in the died did not reproduce the inhibitory effect of iodide. The effect of iodide in vitro on the thyroid cAMP response to TSH was then investigated using paired thyroid lobes obtained from intact rats fed a low-iodine diet. During a 15-min incubation period, concentrations of iodide up to 10(-3)M, together with TSH (125 mU/ml), did not affect the thyroid cAMP response to TSH. In contrast, the preincubation of the lobes in 5 X 10(-5)M Nal for 2 h preceding a final 15-min incubation in medium containing TSH alone resulted in final cAMP concentrations significantly lower than those in paired lobes not exposed to iodide. Basal cAMP concentrations in thyroids not subjected to TSH stimulation were unaffected by preincubation in iodide. The inclusion of TSH during the preincubation period augmented the inhibitory effect of iodide on the final thyroid cAMP concentration achieved. The inclusion of MMI together with iodide during the preincubation period abolished the inhibitory effect of iodide on the final cAMP concentration achieved by TSH stimulation. Direct measurement of newly formed organic iodine in vitro demonstrated it to be inversely proportional to the final cAMP concentration achieved by TSH stimulation. The preincubation of thyroid lobes in iodide was without effect on the subsequent stimulation of cAMP by PGE1, or on the stimulation by F- of adenylate cyclase activity in the thyroid homogenate. The data support the concept of an as yet unknown organic form of iodine that limits thyroid adenylate cyclase responsiveness to TSH stimulation. This may, in part, explain the diverse, and generally inhibitory, actions of iodide on thyroid function."} {"id": "PMID:181237", "title": "Effect of pharmacological blockade of ACTH and TSH secretion on the acute stimulation of prolactin release by exposure to cold and ether stress.", "content": "Acute exposure of male rats to cold (5C)leads to a rapid increase of plasma levels of thyrotropin (TSH), prolactin (PRL), corticosterone, and L-thyroxine. Exposure to ether is similarly followed by a rapid increase of plasma levels of PRL and corticosterone, while TSH release is inhibited. Acute treatment with dexamethasone (500 mug) inhibits almost completely the PRL response to both exposure to cold and ether stress, while the plasma TSH response to cold is only delayed and the decrease of plasma TSH observed after ether stress is unchanged. Basal plasma levels of both TSH and PRL are lowered after treatment with the steroid. Thyroxine treatment lowers the plasma TSH concentration to undetectable levels without affecting the plasma PRL response to cold or ether exposure. The present data suggest that the rise of plasma PRL observed after cold exposure is not related to TRH and may suggest that common mechanisms control ACTH and PRL secretion during acute stress exposure.", "contents": "Effect of pharmacological blockade of ACTH and TSH secretion on the acute stimulation of prolactin release by exposure to cold and ether stress. Acute exposure of male rats to cold (5C)leads to a rapid increase of plasma levels of thyrotropin (TSH), prolactin (PRL), corticosterone, and L-thyroxine. Exposure to ether is similarly followed by a rapid increase of plasma levels of PRL and corticosterone, while TSH release is inhibited. Acute treatment with dexamethasone (500 mug) inhibits almost completely the PRL response to both exposure to cold and ether stress, while the plasma TSH response to cold is only delayed and the decrease of plasma TSH observed after ether stress is unchanged. Basal plasma levels of both TSH and PRL are lowered after treatment with the steroid. Thyroxine treatment lowers the plasma TSH concentration to undetectable levels without affecting the plasma PRL response to cold or ether exposure. The present data suggest that the rise of plasma PRL observed after cold exposure is not related to TRH and may suggest that common mechanisms control ACTH and PRL secretion during acute stress exposure."} {"id": "PMID:181238", "title": "Evidence that cyclic AMP is not involved in the chronotropic action of glucagon in the adult mouse heart.", "content": "The effects of glucagon on the adult mouse heart have been studied. Glucagon (1 mg/kg) increased heart rate in the adult mouse. This effect was enhanced in animals which had pretreated with reserpine to deplete catecholamines. No change in the cardiac cyclic AMP concentration after the injection of glucagon was seen in the hearts of reserpinized animals. Moreover, adenylyl cyclase activity, measured in two different laboratories in whole homogenates, 600 X g pellets or washed particles from adult mouse hearts, was not activated by glucagon. Finally, the injection of epinephrine (1.6 mg/kg), but not of glucagon (1.0 mg/kg), increased the per cent of cardiac phosphorylase a activity and depleted cardiac glucogen. Since increased levels of cyclic AMP are associated with an increase in the per cent of the cardiac phosphorylase a activity, these experiments provide evidence for the hypothesis that cyclic AMP is not essential for the rate effects of glucagon in the adult mouse.", "contents": "Evidence that cyclic AMP is not involved in the chronotropic action of glucagon in the adult mouse heart. The effects of glucagon on the adult mouse heart have been studied. Glucagon (1 mg/kg) increased heart rate in the adult mouse. This effect was enhanced in animals which had pretreated with reserpine to deplete catecholamines. No change in the cardiac cyclic AMP concentration after the injection of glucagon was seen in the hearts of reserpinized animals. Moreover, adenylyl cyclase activity, measured in two different laboratories in whole homogenates, 600 X g pellets or washed particles from adult mouse hearts, was not activated by glucagon. Finally, the injection of epinephrine (1.6 mg/kg), but not of glucagon (1.0 mg/kg), increased the per cent of cardiac phosphorylase a activity and depleted cardiac glucogen. Since increased levels of cyclic AMP are associated with an increase in the per cent of the cardiac phosphorylase a activity, these experiments provide evidence for the hypothesis that cyclic AMP is not essential for the rate effects of glucagon in the adult mouse."} {"id": "PMID:181239", "title": "Glucocorticoid receptors: evidence for a second, non-glucocorticoid binding site.", "content": "Previous studies on cytoplasmic glucocorticoid receptors and enzyme induction led to the classification of steroids as inducers (optimal or sub-optimal), antagonists, or inactive steroids, with respect to their activity as glucocorticoids. The receptor was postulated to exist in allosteric equilibrium between two conformational states, one \"active\" and the other \"inactive\". Steroids behaved as inducers (optimal or sub-optimal), antagonists, or inactive steroids depending on their relative affinity for the active and inactive conformational state of the receptor. Another possible model would invoke multiple binding sites on a single receptor with interactions between the binding sites depending upon the particular steroid bound. To test this latter possibility, an experimental technique was developed to measure the rate of dissociation of tritiated dexamethasone ([3H]DM) or tritiated aldosterone ([3H]A) from the glucocorticoid receptor of rat liver or kidney cytosol. The dissociation of the [3H]DM-receptor at 25 C was not due to irreversible denaturation, and minimal recombination of the receptor with [3H]DM occurred. Progesterone and a number of other steroids consistently and significantly increased the dissociation rate of [3H]DM-receptor complexes in both liver and kidney cytosol. An identical effect was seen with hepatic glucocorticoid receptors labelled with [3H]A, like dexamethasone an optimal inducer. All steroids which enhanced glucocorticoid-receptor dissociation were either antagonists or sub-optimal inducers. Thus, it is postulated that glucocorticoid receptors have at least two classes of binding sites, and that occupation of the second site increases the dissociation rate of agonists from glucocorticoid receptors.", "contents": "Glucocorticoid receptors: evidence for a second, non-glucocorticoid binding site. Previous studies on cytoplasmic glucocorticoid receptors and enzyme induction led to the classification of steroids as inducers (optimal or sub-optimal), antagonists, or inactive steroids, with respect to their activity as glucocorticoids. The receptor was postulated to exist in allosteric equilibrium between two conformational states, one \"active\" and the other \"inactive\". Steroids behaved as inducers (optimal or sub-optimal), antagonists, or inactive steroids depending on their relative affinity for the active and inactive conformational state of the receptor. Another possible model would invoke multiple binding sites on a single receptor with interactions between the binding sites depending upon the particular steroid bound. To test this latter possibility, an experimental technique was developed to measure the rate of dissociation of tritiated dexamethasone ([3H]DM) or tritiated aldosterone ([3H]A) from the glucocorticoid receptor of rat liver or kidney cytosol. The dissociation of the [3H]DM-receptor at 25 C was not due to irreversible denaturation, and minimal recombination of the receptor with [3H]DM occurred. Progesterone and a number of other steroids consistently and significantly increased the dissociation rate of [3H]DM-receptor complexes in both liver and kidney cytosol. An identical effect was seen with hepatic glucocorticoid receptors labelled with [3H]A, like dexamethasone an optimal inducer. All steroids which enhanced glucocorticoid-receptor dissociation were either antagonists or sub-optimal inducers. Thus, it is postulated that glucocorticoid receptors have at least two classes of binding sites, and that occupation of the second site increases the dissociation rate of agonists from glucocorticoid receptors."} {"id": "PMID:181240", "title": "The porcine ovarian follicle: III. Development of chorionic gonadotropin receptors associated with increase in adenyl cyclase activity during follicle maturation.", "content": "Specific binding of human chorionic gonadotropin (hCG), and the hCG-sensitive adenyl cyclase of granulosa cells from small (1-2 mm), medium (3-5 mm), and large (6-12 mm) porcine ovarian follicles have been studied. The number of hCG-binding sites per cell (n) increases during follicle maturation without a change in the binding affinity. The values for n were 300-400 for small, 1,000-1,600 for medium, and 8,200-10,000 for large-follicle cells. The dissociation constant is 2.4 X 10(-10)M for all cells. hCG-sensitive adenyl cyclase was demonstrated in porcine granulosa cells. The adenyl cyclase system of granulosa cells becomes increasingly responsive to hCG stimulation during follicle development. Maximal adenyl cyclase activation by hCG (1 mug/ml) was 240, 750, and 7,000 molecules of cyclic AMP formed/sec/cell, respectively, for small, medium, and large follicle cell. The concentration of hCG giving half-maximal stimulation (1.0 X 10(-9)M) was similar for both large and medium follicle cells. It is concluded that: 1) an increase in hCG receptor sites per cell occurs during maturation of the porcine ovarian follicle without change of binding affinity, and 2) the increase in the number of hCG receptors correlates well with hCG-sensitive adenyl cyclase activity during follicle development.", "contents": "The porcine ovarian follicle: III. Development of chorionic gonadotropin receptors associated with increase in adenyl cyclase activity during follicle maturation. Specific binding of human chorionic gonadotropin (hCG), and the hCG-sensitive adenyl cyclase of granulosa cells from small (1-2 mm), medium (3-5 mm), and large (6-12 mm) porcine ovarian follicles have been studied. The number of hCG-binding sites per cell (n) increases during follicle maturation without a change in the binding affinity. The values for n were 300-400 for small, 1,000-1,600 for medium, and 8,200-10,000 for large-follicle cells. The dissociation constant is 2.4 X 10(-10)M for all cells. hCG-sensitive adenyl cyclase was demonstrated in porcine granulosa cells. The adenyl cyclase system of granulosa cells becomes increasingly responsive to hCG stimulation during follicle development. Maximal adenyl cyclase activation by hCG (1 mug/ml) was 240, 750, and 7,000 molecules of cyclic AMP formed/sec/cell, respectively, for small, medium, and large follicle cell. The concentration of hCG giving half-maximal stimulation (1.0 X 10(-9)M) was similar for both large and medium follicle cells. It is concluded that: 1) an increase in hCG receptor sites per cell occurs during maturation of the porcine ovarian follicle without change of binding affinity, and 2) the increase in the number of hCG receptors correlates well with hCG-sensitive adenyl cyclase activity during follicle development."} {"id": "PMID:181241", "title": "Renin activity in dog brain: enzymological similarity to cathepsin D.", "content": "The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.", "contents": "Renin activity in dog brain: enzymological similarity to cathepsin D. The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions."} {"id": "PMID:181242", "title": "The effect of experimentally induced focal epilepsy on operant responding in the rat.", "content": "Dose-response studies were performed on freely moving rats bearing chronically implanted electrodes. The effects of intracortical injections of penicillin, bicuculline, and conjugated estrogens (Premarin) were determined on EEG activity and motor performance. Bicuculline in doses of 0.025 and 0.05% regularly produced spike and afterdischarge (AD) patterns of rapid onset (less than 10 sec,) brief duration (less than 20 min), and marked intensity. Lower doses had little or no effect. Premarin 1% and penicillin 100 international units produced spike and AD patterns of slower onset (5 min), longer duration (up to 2 hr), and mild intensity. Smaller doses generally produced no AD activity, whereas larger doses produced epileptic patterns severe enough to preclude their use in operant studies. Penicillin and Premarin both produced a significant decrease in operant-response rate in animals trained to bar press on a FR 20 schedule. A marked variability was noted in the behavioral responses of individual rats to the disruptive effects of the epileptogens.", "contents": "The effect of experimentally induced focal epilepsy on operant responding in the rat. Dose-response studies were performed on freely moving rats bearing chronically implanted electrodes. The effects of intracortical injections of penicillin, bicuculline, and conjugated estrogens (Premarin) were determined on EEG activity and motor performance. Bicuculline in doses of 0.025 and 0.05% regularly produced spike and afterdischarge (AD) patterns of rapid onset (less than 10 sec,) brief duration (less than 20 min), and marked intensity. Lower doses had little or no effect. Premarin 1% and penicillin 100 international units produced spike and AD patterns of slower onset (5 min), longer duration (up to 2 hr), and mild intensity. Smaller doses generally produced no AD activity, whereas larger doses produced epileptic patterns severe enough to preclude their use in operant studies. Penicillin and Premarin both produced a significant decrease in operant-response rate in animals trained to bar press on a FR 20 schedule. A marked variability was noted in the behavioral responses of individual rats to the disruptive effects of the epileptogens."} {"id": "PMID:181243", "title": "Biphasic effects of imipramine in experimental models of epilepsy.", "content": "In a variety of laboratory models of experimental epilepsy, imipramine exerts a biphasic action on the CNS as manifested by antiepileptic properties at low doses and convulsant effects at higher doses. In mice, imipramine (17.5-25 mg/kg, i.p.) blocks maximal electroshock seizures while exerting little or no effect on pentylenetetrazol-induced seizures. In cats, imipramine (2.5-15 mg/kg, i.v.) reduces penicillin and estrogen-induced epileptiform discharge, shortens afterdischarge duration and elevates afterdischarge threshold. Higher doses in mice induce neurotoxicity, including clonic seizures. In cats, doses above 20 mg/kg intensify chemically and electrically induced seizures and induce spontaneous epileptiform episodes. Such a biphasic action of imipramine may limit the drug's clinical utility as an antiepileptic agent and may provide an interesting tool for studies of catecholamines and brain excitability.", "contents": "Biphasic effects of imipramine in experimental models of epilepsy. In a variety of laboratory models of experimental epilepsy, imipramine exerts a biphasic action on the CNS as manifested by antiepileptic properties at low doses and convulsant effects at higher doses. In mice, imipramine (17.5-25 mg/kg, i.p.) blocks maximal electroshock seizures while exerting little or no effect on pentylenetetrazol-induced seizures. In cats, imipramine (2.5-15 mg/kg, i.v.) reduces penicillin and estrogen-induced epileptiform discharge, shortens afterdischarge duration and elevates afterdischarge threshold. Higher doses in mice induce neurotoxicity, including clonic seizures. In cats, doses above 20 mg/kg intensify chemically and electrically induced seizures and induce spontaneous epileptiform episodes. Such a biphasic action of imipramine may limit the drug's clinical utility as an antiepileptic agent and may provide an interesting tool for studies of catecholamines and brain excitability."} {"id": "PMID:181245", "title": "Three major forms of adenylate kinase from adult and fetal rat tissues.", "content": "The major enzymatic forms of adenylate kinase have been purified to homogeneity from fetal liver and adult brain of the rat. The two enzymes differ with respect to isoelectric points, Km (ATP), Km (AMP), and Ka (citrate). Antibody to adult liver adenylate kinase does not inhibit either enzyme, while entibody to adult skeletal muscle enzyme inhibits the brain enzyme but not the fetal liver enzyme. It is therefore probable that there are three major forms of adenylate kinases in fetal and adult rat tissues.", "contents": "Three major forms of adenylate kinase from adult and fetal rat tissues. The major enzymatic forms of adenylate kinase have been purified to homogeneity from fetal liver and adult brain of the rat. The two enzymes differ with respect to isoelectric points, Km (ATP), Km (AMP), and Ka (citrate). Antibody to adult liver adenylate kinase does not inhibit either enzyme, while entibody to adult skeletal muscle enzyme inhibits the brain enzyme but not the fetal liver enzyme. It is therefore probable that there are three major forms of adenylate kinases in fetal and adult rat tissues."} {"id": "PMID:181246", "title": "Poly(A) hydrolase of chick-embryo fibroblasts.", "content": "1. Homogenates of cultured chick embryo fibroblasts have been quantitatively fractionated by differential centrifugation. Using cytochrome c oxidase, succinate dehydrogenase, acid phosphatase and NADPH-cytochrome c reductase as marker enzymes, poly(A) hydrolase has been shown to be a mitochondrial enzyme. 2. To test the biosynthetic origin of mitochondrial poly(A) hydrolase and to demonstrate its cytoplasmic site of synthesis, we have treated the cells with ethidium bromide, inhibitor of mitochondrial transcription, and chloramphenicol and cycloheximide, inhibitors of mitochondrial and cytoplasmic translations respectively. The activity of poly(A) hydrolase has been compared to that of succinate dehydrogenase, an enzyme coded for by the nuclear genome and that of cytochrome c oxidase, an enzyme coded for partly by the nuclear genome and partly by the mitochondrial genome. The results obtained indicate that in chick embryo fibroblasts poly(A) hydrolase is an enzyme coded for by the nuclear genome. Further, the hydrolase is synthesized on cytoplasmic ribosomes and has a half-life much shorter than succinate dehydrogenase and cytochrome c oxidase.", "contents": "Poly(A) hydrolase of chick-embryo fibroblasts. 1. Homogenates of cultured chick embryo fibroblasts have been quantitatively fractionated by differential centrifugation. Using cytochrome c oxidase, succinate dehydrogenase, acid phosphatase and NADPH-cytochrome c reductase as marker enzymes, poly(A) hydrolase has been shown to be a mitochondrial enzyme. 2. To test the biosynthetic origin of mitochondrial poly(A) hydrolase and to demonstrate its cytoplasmic site of synthesis, we have treated the cells with ethidium bromide, inhibitor of mitochondrial transcription, and chloramphenicol and cycloheximide, inhibitors of mitochondrial and cytoplasmic translations respectively. The activity of poly(A) hydrolase has been compared to that of succinate dehydrogenase, an enzyme coded for by the nuclear genome and that of cytochrome c oxidase, an enzyme coded for partly by the nuclear genome and partly by the mitochondrial genome. The results obtained indicate that in chick embryo fibroblasts poly(A) hydrolase is an enzyme coded for by the nuclear genome. Further, the hydrolase is synthesized on cytoplasmic ribosomes and has a half-life much shorter than succinate dehydrogenase and cytochrome c oxidase."} {"id": "PMID:181247", "title": "Protein phosphorylation of the smooth and rough endoplasmic reticulum in normal and neoplastic liver of the rat.", "content": "Smooth and rough endoplasmic reticulum from rat liver and hepatomas exhibited endogenous protein kinase activity independent of adenosine 3':5'-monophosphate. The phosphorylation of smooth membranes by this process was consistently higher than that of rough membranes. When histone was added along with the smooth endoplasmic reticulum, cyclic AMP stimulated protein phosphorylation. Analysis of membrane-phosphorylated proteins by gel electrophoresis showed 5 major phosphorylated bands with estimated molecular weights of 155 000, 62 000, 50 000, 46 000 and 43 000, whereas major bands having estimated molecular weights of 62 000, 50 000 and 43 000 were found in membranes of the smooth endoplasmic reticulum of the Morris hepatoma 5123 C. Since previous studies in this and other laboratories have demonstrated the similarity of the protein components of membranes of the endoplasmic reticulum of normal liver and hepatoma, our findings indicate an inability of the protein kinase of hepatoma intracellular membranes to phosphorylate protein species that are found in membranes of both liver and the neoplasm.", "contents": "Protein phosphorylation of the smooth and rough endoplasmic reticulum in normal and neoplastic liver of the rat. Smooth and rough endoplasmic reticulum from rat liver and hepatomas exhibited endogenous protein kinase activity independent of adenosine 3':5'-monophosphate. The phosphorylation of smooth membranes by this process was consistently higher than that of rough membranes. When histone was added along with the smooth endoplasmic reticulum, cyclic AMP stimulated protein phosphorylation. Analysis of membrane-phosphorylated proteins by gel electrophoresis showed 5 major phosphorylated bands with estimated molecular weights of 155 000, 62 000, 50 000, 46 000 and 43 000, whereas major bands having estimated molecular weights of 62 000, 50 000 and 43 000 were found in membranes of the smooth endoplasmic reticulum of the Morris hepatoma 5123 C. Since previous studies in this and other laboratories have demonstrated the similarity of the protein components of membranes of the endoplasmic reticulum of normal liver and hepatoma, our findings indicate an inability of the protein kinase of hepatoma intracellular membranes to phosphorylate protein species that are found in membranes of both liver and the neoplasm."} {"id": "PMID:181248", "title": "Nitrate reductase from Chlorella vulgaris. Reaction with manganese (III) pyrophosphate and with ferric o-phenanthroline.", "content": "Millimolar concentrations of tervalent manganese pyrophosphate can partially activate nitrate reductase which has been inactivated with NADH and HCN. The tervalent manganese complex is nevertheless not reduced by NADH in the presence of the enzyme, that is, it is not a substrate for the diaphorase moiety of the nitrate reductase. Ferric o-phenanthroline, on the other hand, is a good diaphorase substrate, but fails to activate the inactive enzyme.", "contents": "Nitrate reductase from Chlorella vulgaris. Reaction with manganese (III) pyrophosphate and with ferric o-phenanthroline. Millimolar concentrations of tervalent manganese pyrophosphate can partially activate nitrate reductase which has been inactivated with NADH and HCN. The tervalent manganese complex is nevertheless not reduced by NADH in the presence of the enzyme, that is, it is not a substrate for the diaphorase moiety of the nitrate reductase. Ferric o-phenanthroline, on the other hand, is a good diaphorase substrate, but fails to activate the inactive enzyme."} {"id": "PMID:181249", "title": "Glycopeptides from bovine liver basement membrane and plasma membrane.", "content": "Proteolytic digests of liver plasma-cell membranes from the cow were fractionated to yield two homogeneous glycopeptides and a third preparation about 92% pure. The composition of the two homogeneous glycopeptides made it clear that they were derived from basement membrane material rather than the plasma membrane. Ruminants are unusual in having large amounts of basement membrane in the liver while other animals generally have little or none. Both basement-membrane-derived glycopeptides contained a glucosyl galactosyl disaccharide linked to hydroxylysine, the smaller one contained no other sugar structure but the larger one contained in addition an acidic heterosaccharide, the two chains probably being linked separately to the same molecule. Smith degradation and beta-elimination operations show that this heterosaccharide has an inner structure containing mannose and hexosamine, with the sugars galactose, N-glycollyl-neuraminic acid and fucose situated more peripherally. The amino-acid-heterosaccharide linkage is alkali stable. The third glycopeptide, which may be plasma-membrane-derived, differs from the heterosaccharide described above in that it contains no glucose and contains some O-seryl and O-threonyl amino-acid--sugar linkage. It, too, has a periodate-resistant structure of hexosamine and mannose.", "contents": "Glycopeptides from bovine liver basement membrane and plasma membrane. Proteolytic digests of liver plasma-cell membranes from the cow were fractionated to yield two homogeneous glycopeptides and a third preparation about 92% pure. The composition of the two homogeneous glycopeptides made it clear that they were derived from basement membrane material rather than the plasma membrane. Ruminants are unusual in having large amounts of basement membrane in the liver while other animals generally have little or none. Both basement-membrane-derived glycopeptides contained a glucosyl galactosyl disaccharide linked to hydroxylysine, the smaller one contained no other sugar structure but the larger one contained in addition an acidic heterosaccharide, the two chains probably being linked separately to the same molecule. Smith degradation and beta-elimination operations show that this heterosaccharide has an inner structure containing mannose and hexosamine, with the sugars galactose, N-glycollyl-neuraminic acid and fucose situated more peripherally. The amino-acid-heterosaccharide linkage is alkali stable. The third glycopeptide, which may be plasma-membrane-derived, differs from the heterosaccharide described above in that it contains no glucose and contains some O-seryl and O-threonyl amino-acid--sugar linkage. It, too, has a periodate-resistant structure of hexosamine and mannose."} {"id": "PMID:181250", "title": "Spectroscopic investigation of binary and ternary coenzyme complexes of yeast alcohol dehydrogenase.", "content": "Corrected fluorescence properties of yeast alcohol dehydrogenase and its coenzyme complexes have been investigated as a function of temperature. Dissociation constants have been obtained for binary and ternary complexes of NAD and NADH by following the enhancement of NADH fluorescence or the quenching of the protein fluorescence. It is found that the presence of pyrazole increases the affinity of NAD to the enzyme approximately 100-fold. The formation of the ternary enzyme - NAD - pyrazole complex is accompanied by a large change in the ultraviolet absorption properties, with a new band in the 290-nm region. Significant optical changes also accompany the formation of the ternary enzyme-NADH-acetamide complex. The possible origin for the quenching of the protein fluorescence upon coenzyme binding is discussed, and it is suggested that a coenzyme-induced conformational change can cause it. Thermodynamic parameters associated with NAD and NADH binding have been evaluated on the basis of the change of the dissociation constants with temperature. Optical and thermodynamic properties of binary and ternary complexes of yeast alcohol dehydrogenase are compared with the analogous properties of horse liver alcohol dehydrogenase.", "contents": "Spectroscopic investigation of binary and ternary coenzyme complexes of yeast alcohol dehydrogenase. Corrected fluorescence properties of yeast alcohol dehydrogenase and its coenzyme complexes have been investigated as a function of temperature. Dissociation constants have been obtained for binary and ternary complexes of NAD and NADH by following the enhancement of NADH fluorescence or the quenching of the protein fluorescence. It is found that the presence of pyrazole increases the affinity of NAD to the enzyme approximately 100-fold. The formation of the ternary enzyme - NAD - pyrazole complex is accompanied by a large change in the ultraviolet absorption properties, with a new band in the 290-nm region. Significant optical changes also accompany the formation of the ternary enzyme-NADH-acetamide complex. The possible origin for the quenching of the protein fluorescence upon coenzyme binding is discussed, and it is suggested that a coenzyme-induced conformational change can cause it. Thermodynamic parameters associated with NAD and NADH binding have been evaluated on the basis of the change of the dissociation constants with temperature. Optical and thermodynamic properties of binary and ternary complexes of yeast alcohol dehydrogenase are compared with the analogous properties of horse liver alcohol dehydrogenase."} {"id": "PMID:181251", "title": "NADH-dependent aryl hydrocarbon hydroxylase in rat liver mitochondrial outer membrane.", "content": "NADH-dependent 3,4-benzpyrene hydroxylase activity was detected in the purified mitochondrial outer membrane fraction from the livers of rats treated with 3-methylcholanthrene. The specific activity in the outer membrane fraction is nearly equal to that of microsomes, a level too high to be accounted for only by the microsomal contamination. On the other hand, the NADPH-dependent 3,4-benzpyrene hydroxylase activity in the outer membrane fraction is about 50% of that of microsomes. The ratio of the specific activity of NADPH- to NADH-dependent 3,4-benzpyrene hydroxylase in microsomal fraction was about 3.5, while that of the outer membrane fraction was about 1.5. Moreover, it was found that NADH-dependent 3,4-benzpyrene hydroxylase activity in mitochondrial outer membrane from control rat liver was cyanide-insensitive, while that in microsomes was cyanide-sensitive. These results suggest the presence in the mitochondrial outer membrane fraction of aryl hydrocarbon hydroxylase activity which uses as electron donor NADH nearly to the same extent as NADPH. The hydroxylase system is composed of cyanide-insensitive cytochrome P-450 and is inducible markedly by 3-methylcholanthrene treatment. The probable electron transfer pathways in the mitochondrial outer membrane cytochrome P-450 oxidase system are discussed.", "contents": "NADH-dependent aryl hydrocarbon hydroxylase in rat liver mitochondrial outer membrane. NADH-dependent 3,4-benzpyrene hydroxylase activity was detected in the purified mitochondrial outer membrane fraction from the livers of rats treated with 3-methylcholanthrene. The specific activity in the outer membrane fraction is nearly equal to that of microsomes, a level too high to be accounted for only by the microsomal contamination. On the other hand, the NADPH-dependent 3,4-benzpyrene hydroxylase activity in the outer membrane fraction is about 50% of that of microsomes. The ratio of the specific activity of NADPH- to NADH-dependent 3,4-benzpyrene hydroxylase in microsomal fraction was about 3.5, while that of the outer membrane fraction was about 1.5. Moreover, it was found that NADH-dependent 3,4-benzpyrene hydroxylase activity in mitochondrial outer membrane from control rat liver was cyanide-insensitive, while that in microsomes was cyanide-sensitive. These results suggest the presence in the mitochondrial outer membrane fraction of aryl hydrocarbon hydroxylase activity which uses as electron donor NADH nearly to the same extent as NADPH. The hydroxylase system is composed of cyanide-insensitive cytochrome P-450 and is inducible markedly by 3-methylcholanthrene treatment. The probable electron transfer pathways in the mitochondrial outer membrane cytochrome P-450 oxidase system are discussed."} {"id": "PMID:181252", "title": "Limited proteolysis of cytoplasmic and nuclear uterine estradiol receptors yields identical estradiol-binding fragments.", "content": "Limited tryptic hydrolysis of the estradiol cytoplasmic receptor from calf uterus has been demonstrated to yield in a high-salt buffer a stable estradiol-binding molecule with the following characteristics: sedimentation coefficient 4.0 +/- 0.1 S; Stokes radius 3.5 +/- 0.05 nm; molecular weight 60000 (for an assumed v value of 0.73 ml g-1) and frictional ratio 1.36. Nuclear KCl extracts, prepared from uteri preincubated at 37 degrees C with labeled estradiol, were analysed by Sephadex G-200 chromatography and sucrose density gradient centrifugation. The following molecular parameters were found for the estradiol-receptor complex: sedimentation coefficient 4.4 +/- 0.1 S; Stokes radius 4.12 +/- 0.02 nm; molecular weight 77000 and frictional ratio 1.47 (v = 0.73 ml g-1). Limited tryptic proteolysis of this extract gave an estradiol-binding fragment with molecular characteristics identical to the trypsin-modified cytoplasmic receptor. In addition, mild tryptic digestion of whole labeled nuclei allowed us to solubilize almost quantitatively the nuclear [3H]estradiol in a macromolecular bound form. The molecule thus obtained showed molecular parameters very similar to the 60000-dalton trypsin fragments obtained from high-salt cytoplasmic and nuclear extracts. These molecules were undistinguishable by gel electrophoresis analysis at six different acrylamide concentrations. These results in conjunction with those derived from dissociation kinetics experiments and ligand specificity studies indicate the cytosolic protein is a functional part of the nuclear receptor. Based upon these and other studies we suggest that proteolytic cleavage of the estradiol-receptor complex, which results in the removal of the estradiol-binding sites from the nuclear recognition sites of the molecule, could play a role in the inactivation of the estradiol receptor in vivo.", "contents": "Limited proteolysis of cytoplasmic and nuclear uterine estradiol receptors yields identical estradiol-binding fragments. Limited tryptic hydrolysis of the estradiol cytoplasmic receptor from calf uterus has been demonstrated to yield in a high-salt buffer a stable estradiol-binding molecule with the following characteristics: sedimentation coefficient 4.0 +/- 0.1 S; Stokes radius 3.5 +/- 0.05 nm; molecular weight 60000 (for an assumed v value of 0.73 ml g-1) and frictional ratio 1.36. Nuclear KCl extracts, prepared from uteri preincubated at 37 degrees C with labeled estradiol, were analysed by Sephadex G-200 chromatography and sucrose density gradient centrifugation. The following molecular parameters were found for the estradiol-receptor complex: sedimentation coefficient 4.4 +/- 0.1 S; Stokes radius 4.12 +/- 0.02 nm; molecular weight 77000 and frictional ratio 1.47 (v = 0.73 ml g-1). Limited tryptic proteolysis of this extract gave an estradiol-binding fragment with molecular characteristics identical to the trypsin-modified cytoplasmic receptor. In addition, mild tryptic digestion of whole labeled nuclei allowed us to solubilize almost quantitatively the nuclear [3H]estradiol in a macromolecular bound form. The molecule thus obtained showed molecular parameters very similar to the 60000-dalton trypsin fragments obtained from high-salt cytoplasmic and nuclear extracts. These molecules were undistinguishable by gel electrophoresis analysis at six different acrylamide concentrations. These results in conjunction with those derived from dissociation kinetics experiments and ligand specificity studies indicate the cytosolic protein is a functional part of the nuclear receptor. Based upon these and other studies we suggest that proteolytic cleavage of the estradiol-receptor complex, which results in the removal of the estradiol-binding sites from the nuclear recognition sites of the molecule, could play a role in the inactivation of the estradiol receptor in vivo."} {"id": "PMID:181253", "title": "Carboxymethylated liver alcohol dehydrogenase. Transient kinetic studies and effect of substrate structure on alcohol oxidation.", "content": "1. The rate constants for NADH binding and dissociation for carboxymethylated alcohol dehydrogenase have been determined and compared to those for the native enzyme. 2. Steady-state and transient kinetic experiments have shown that the hydrogen transfer step is rate-determining for oxidation of ethanol by carboxymethylated alcohol dehydrogenase. The rate constant of 0.19 s-1 is considerably slower than that for the native enzyme. 3. The steady-state parameter, V/[E], was obtained for each of a series of alcohols and correlated with the Taft sigma parameter. The linear relationship obtained indicates that the same step, hydrogen transfer, is rate-determining for all the alcohols. The sigma value obtained is the same as for the native enzyme; the implications of this for the mechanism of hydrogen transfer are discussed.", "contents": "Carboxymethylated liver alcohol dehydrogenase. Transient kinetic studies and effect of substrate structure on alcohol oxidation. 1. The rate constants for NADH binding and dissociation for carboxymethylated alcohol dehydrogenase have been determined and compared to those for the native enzyme. 2. Steady-state and transient kinetic experiments have shown that the hydrogen transfer step is rate-determining for oxidation of ethanol by carboxymethylated alcohol dehydrogenase. The rate constant of 0.19 s-1 is considerably slower than that for the native enzyme. 3. The steady-state parameter, V/[E], was obtained for each of a series of alcohols and correlated with the Taft sigma parameter. The linear relationship obtained indicates that the same step, hydrogen transfer, is rate-determining for all the alcohols. The sigma value obtained is the same as for the native enzyme; the implications of this for the mechanism of hydrogen transfer are discussed."} {"id": "PMID:181255", "title": "Cardiac slowing and respiratory arrest in preterm infants.", "content": "Changes in respiration and heart rate during sleep states have been recorded by a polygraphic device in healthy preterm infants. Cardiac slowing/bradycardia often coincide with respiratory arrest/apnea. Bradycardia starts early during apneic spells. The incidence of respiratory arrest and cardiac slowing and their simultaneous occurrence is significantly increased by the active or REM sleep state. The physiologic, inhibitory mechanisms of active sleep suggest a neurogenic etiology of episodes of cardiac slowing/bradycardia and/or respiratory arrest/apnea in prematures.", "contents": "Cardiac slowing and respiratory arrest in preterm infants. Changes in respiration and heart rate during sleep states have been recorded by a polygraphic device in healthy preterm infants. Cardiac slowing/bradycardia often coincide with respiratory arrest/apnea. Bradycardia starts early during apneic spells. The incidence of respiratory arrest and cardiac slowing and their simultaneous occurrence is significantly increased by the active or REM sleep state. The physiologic, inhibitory mechanisms of active sleep suggest a neurogenic etiology of episodes of cardiac slowing/bradycardia and/or respiratory arrest/apnea in prematures."} {"id": "PMID:181254", "title": "The influence of phenobarbital on carbohydrate metabolism in developing rat liver.", "content": "The influences of phenobarbital (PB) on enzymes of the carbohydrate metabolism in rat liver are examined during pre- and postnatal development. The following results are obtained: (1) PB generally increases G-6-Pase before and after birth. (2) Both the active and the inactive forms of phosphorylase are increased significantly during the prenatal periods. During the postnatal periods, mainly the active form of phosphorylase is influenced by PB. (3) Total glycogen synthetase is increased by PB during prenatal development but decreased during postnatal development. (4) The activity of alpha-glucosidase is increased during the prenatal period. (5) The activity of F-6-PK and 6-PGDH are decreased during the prenatal periods and G-6-PDH activity is decreased during both pre- and postnatal periods.", "contents": "The influence of phenobarbital on carbohydrate metabolism in developing rat liver. The influences of phenobarbital (PB) on enzymes of the carbohydrate metabolism in rat liver are examined during pre- and postnatal development. The following results are obtained: (1) PB generally increases G-6-Pase before and after birth. (2) Both the active and the inactive forms of phosphorylase are increased significantly during the prenatal periods. During the postnatal periods, mainly the active form of phosphorylase is influenced by PB. (3) Total glycogen synthetase is increased by PB during prenatal development but decreased during postnatal development. (4) The activity of alpha-glucosidase is increased during the prenatal period. (5) The activity of F-6-PK and 6-PGDH are decreased during the prenatal periods and G-6-PDH activity is decreased during both pre- and postnatal periods."} {"id": "PMID:181256", "title": "Chromosome abnormalities in neurological diseases.", "content": "The current status of research into chromosomal abnormalities in neurological diseases is reviewed. The only possible association between chromosome aberration and neurological disorder is found in ataxia telangiectasia and in tumours of the nervous system. In the remaining diseases reviewed, no specific association was confirmed. This was expected to some extent, since the majority of these diseases (spinal muscular atrophies, muscular dystrophies, etc.) are due to single gene defects.", "contents": "Chromosome abnormalities in neurological diseases. The current status of research into chromosomal abnormalities in neurological diseases is reviewed. The only possible association between chromosome aberration and neurological disorder is found in ataxia telangiectasia and in tumours of the nervous system. In the remaining diseases reviewed, no specific association was confirmed. This was expected to some extent, since the majority of these diseases (spinal muscular atrophies, muscular dystrophies, etc.) are due to single gene defects."} {"id": "PMID:181257", "title": "Hyperlipidemic neuropathy and dementia.", "content": "Mixed types of sensory and motor peripheral neuropathy and dementia occurred as neurological complications in patients with established type IV and type V hyperlipoproteinemia. These complications were remedial by control of the hyperlipoproteinemia with diet and/or clofibrate resulting in symptomatic improvement as well as restitution of nerve conduction velocities toward normal. Diabetes mellitus as well as systemic metabolic and toxic disorders which commonly produce neurological complications were excluded. Segmental demyelination with disorganization of myelin lamellae were striking morphological features found on sural nerve biopsy. Fluctuations in memory performance correlated inversely with plasma lipid levels and appear to be a characteristic feature of hyperlipidemic dementia. Hyperlipidemic neuropathy and dementia, although rare, are remediable neurological disorders which should be considered in patients with neuropathy and/or dementia of unknown origin.", "contents": "Hyperlipidemic neuropathy and dementia. Mixed types of sensory and motor peripheral neuropathy and dementia occurred as neurological complications in patients with established type IV and type V hyperlipoproteinemia. These complications were remedial by control of the hyperlipoproteinemia with diet and/or clofibrate resulting in symptomatic improvement as well as restitution of nerve conduction velocities toward normal. Diabetes mellitus as well as systemic metabolic and toxic disorders which commonly produce neurological complications were excluded. Segmental demyelination with disorganization of myelin lamellae were striking morphological features found on sural nerve biopsy. Fluctuations in memory performance correlated inversely with plasma lipid levels and appear to be a characteristic feature of hyperlipidemic dementia. Hyperlipidemic neuropathy and dementia, although rare, are remediable neurological disorders which should be considered in patients with neuropathy and/or dementia of unknown origin."} {"id": "PMID:181258", "title": "Effects of intravenous phospholipid on low density lipoprotein turnover in man.", "content": "The mechanism of the rise in plasma low density lipoprotein (LDL) levels following intravenous administration of a triglyceride-phospholipid emulsion (Intralipid) has been investigated by measuring LDL turnover in eight healthy subjects. The plasma half-life, and the absolute and fractional catabolic rates of LDL protein (apo-LDL) were unaffected by intragastric Intralipid, whereas apo-LDL half-life was prolonged and its fractional catabolic rate was decreased by intravenous Intralipid. Similar changes were observed after intravenous administration of the egg phospholipid constituent of Intralipid. Accompanying increases in the oleate: linoleate ratio of both high and low density lipoprotein cholesterol esters were secondary to phospholipid exchange between infused and endogenous lecithin. These results suggest that the increased concentration of LDL in plasma following intravenous administration of egg phospholipid-containing emulsions was due, at least in part, to a decrease in the fractional catabolic rate of apo-LDL. The data further suggest a possible relationship between apo-LDL catabolism and the fatty acid composition of LDL.", "contents": "Effects of intravenous phospholipid on low density lipoprotein turnover in man. The mechanism of the rise in plasma low density lipoprotein (LDL) levels following intravenous administration of a triglyceride-phospholipid emulsion (Intralipid) has been investigated by measuring LDL turnover in eight healthy subjects. The plasma half-life, and the absolute and fractional catabolic rates of LDL protein (apo-LDL) were unaffected by intragastric Intralipid, whereas apo-LDL half-life was prolonged and its fractional catabolic rate was decreased by intravenous Intralipid. Similar changes were observed after intravenous administration of the egg phospholipid constituent of Intralipid. Accompanying increases in the oleate: linoleate ratio of both high and low density lipoprotein cholesterol esters were secondary to phospholipid exchange between infused and endogenous lecithin. These results suggest that the increased concentration of LDL in plasma following intravenous administration of egg phospholipid-containing emulsions was due, at least in part, to a decrease in the fractional catabolic rate of apo-LDL. The data further suggest a possible relationship between apo-LDL catabolism and the fatty acid composition of LDL."} {"id": "PMID:181265", "title": "Hydrosoluble immunostimulants of bacterial and synthetic origins.", "content": "The role of whole Mycobacteria, mycobacterial cell walls and waxes D as immunostimulants was well established many years ago. More recently three different research groups have shown that hydrosoluble components from mycobacterial and other bacterial origins were as active as waxes D or cell walls and were free of many side-effects. Studies concerning the relationship between structure and activity were achieved which led to the description of a small biologically active fragment and to a first series of synthetic compounds.", "contents": "Hydrosoluble immunostimulants of bacterial and synthetic origins. The role of whole Mycobacteria, mycobacterial cell walls and waxes D as immunostimulants was well established many years ago. More recently three different research groups have shown that hydrosoluble components from mycobacterial and other bacterial origins were as active as waxes D or cell walls and were free of many side-effects. Studies concerning the relationship between structure and activity were achieved which led to the description of a small biologically active fragment and to a first series of synthetic compounds."} {"id": "PMID:181266", "title": "Hoplonemertine worms -- a new source of pyridine neurotoxins.", "content": "Two pyridine bases were isolated from the marine hoplonemertine Amphiporus angulatus (Fabricius) and identified by mass and PMR-spectroscopy as 2, 3'-bipyridyl and 3, 2'; 3', 2\"; 4\", 3\"'-tetrapyridyl (Nemertelline). Nemertelline, the first tetrapyridyl natural product to be reported, shows a structural resemblance to the tobacco constituent nicotelline. The crustacean toxicity of 2, 3' -bipyridyl is very similar to that of nicotine, but its mammalian toxicity is negligible.", "contents": "Hoplonemertine worms -- a new source of pyridine neurotoxins. Two pyridine bases were isolated from the marine hoplonemertine Amphiporus angulatus (Fabricius) and identified by mass and PMR-spectroscopy as 2, 3'-bipyridyl and 3, 2'; 3', 2\"; 4\", 3\"'-tetrapyridyl (Nemertelline). Nemertelline, the first tetrapyridyl natural product to be reported, shows a structural resemblance to the tobacco constituent nicotelline. The crustacean toxicity of 2, 3' -bipyridyl is very similar to that of nicotine, but its mammalian toxicity is negligible."} {"id": "PMID:181267", "title": "The orthodox-paradoxical sleep cycle in the rat.", "content": "Under the postulated existence of a mechanism regulating the NREM sleep- REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset.", "contents": "The orthodox-paradoxical sleep cycle in the rat. Under the postulated existence of a mechanism regulating the NREM sleep- REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset."} {"id": "PMID:181268", "title": "Altered brain cyclic AMP-responses in rats reared in enriched or impoverished environments.", "content": "The accumulation of radioactive cyclic AMP elicited by various neurohormones has been examined in adenine-labeled telencephalon slices from rats raised in enriched or impoverished environments. Basal levels of cyclic AMP and responses of the brain slice cyclic AMP-generating systems to norepinephrine, isoproterenol and adenosine did not differ between the two group of rats, while responses to prostaglandin E1 were significantly greater with the impoverished group and responses to histamine appeared to be greater with the enriched group.", "contents": "Altered brain cyclic AMP-responses in rats reared in enriched or impoverished environments. The accumulation of radioactive cyclic AMP elicited by various neurohormones has been examined in adenine-labeled telencephalon slices from rats raised in enriched or impoverished environments. Basal levels of cyclic AMP and responses of the brain slice cyclic AMP-generating systems to norepinephrine, isoproterenol and adenosine did not differ between the two group of rats, while responses to prostaglandin E1 were significantly greater with the impoverished group and responses to histamine appeared to be greater with the enriched group."} {"id": "PMID:181269", "title": "Effects of taurine on the transmembrane ionic currents of rat and guinea pig ventricular fibres.", "content": "The effects of taurine on electrical properties of isolated myocardial ventricular fibres were studied in rat and guinea pig. The action potential amplitude was decreased in these species while the plateau and the repolarization phase were not altered. This suggests that simple inspection of the plateau phase is not sensitive enough to pick up changes in outward current since voltage clamp experiments showed that taurine decreased both potassium current and fast inward current. However, the slow inward calcium current remained unchanged with taurine in each species. These results suggest that the inotropic effects of taurine on rat and guinea pig heart contraction already described, were not due to modifications of the cell membrane permeability for calcium. It seems more reasonable to assume that the cardiac actions of this compound result from intracellular changes in calcium availability.", "contents": "Effects of taurine on the transmembrane ionic currents of rat and guinea pig ventricular fibres. The effects of taurine on electrical properties of isolated myocardial ventricular fibres were studied in rat and guinea pig. The action potential amplitude was decreased in these species while the plateau and the repolarization phase were not altered. This suggests that simple inspection of the plateau phase is not sensitive enough to pick up changes in outward current since voltage clamp experiments showed that taurine decreased both potassium current and fast inward current. However, the slow inward calcium current remained unchanged with taurine in each species. These results suggest that the inotropic effects of taurine on rat and guinea pig heart contraction already described, were not due to modifications of the cell membrane permeability for calcium. It seems more reasonable to assume that the cardiac actions of this compound result from intracellular changes in calcium availability."} {"id": "PMID:181270", "title": "The effect of egg phospholipid administration upon liver enzymic activities during ethionine treatment.", "content": "Female rats were injected subcutaneously with ethionine, and enzymic activities of liver membranes (Na+-k+-stimulated ATPase, Mg2+-stimulated ATPase, glucose-6-phosphatase, NADPH: cytochrome c oxido-reductase and NAD-nucleosidase) examined at proper intervals, during the intraperitoneal treatment of an egg phospholipid preparation (EPL). It is shown that EPL is unable to overcome the enzymic changes due to severe ethionine treatment, but is able to facilitate the recovery times after drug withdrawal for all the enzymic activities, except for NAD-nucleosidase. At lower dosage of the drug, the ethionine treatment is able to prevent the observed change of the glucose-6-phosphatase activity but not that of the Mg2+-ATPase. It is suggested that the EPL treatment may modify the chemical composition ahd/or architecture of liver membranes, altered by the ethionine injection, thus acting, at least partially, on the enzymic changes.", "contents": "The effect of egg phospholipid administration upon liver enzymic activities during ethionine treatment. Female rats were injected subcutaneously with ethionine, and enzymic activities of liver membranes (Na+-k+-stimulated ATPase, Mg2+-stimulated ATPase, glucose-6-phosphatase, NADPH: cytochrome c oxido-reductase and NAD-nucleosidase) examined at proper intervals, during the intraperitoneal treatment of an egg phospholipid preparation (EPL). It is shown that EPL is unable to overcome the enzymic changes due to severe ethionine treatment, but is able to facilitate the recovery times after drug withdrawal for all the enzymic activities, except for NAD-nucleosidase. At lower dosage of the drug, the ethionine treatment is able to prevent the observed change of the glucose-6-phosphatase activity but not that of the Mg2+-ATPase. It is suggested that the EPL treatment may modify the chemical composition ahd/or architecture of liver membranes, altered by the ethionine injection, thus acting, at least partially, on the enzymic changes."} {"id": "PMID:181271", "title": "Comparison of the evolution of heme binding and NAD binding proteins.", "content": "Of the 85 three-dimensionally characterized residues of cytochrome b5, 51 are structurally and topologically equivalent to the globin fold. When these proteins have been superimposed, the heme irons are found to be less than 1.4 A separated and the heme normals are inclined by less than 9.5 degrees. Comparison of minimum base changes per codon between heme binding and NAD binding proteins are of the same order.", "contents": "Comparison of the evolution of heme binding and NAD binding proteins. Of the 85 three-dimensionally characterized residues of cytochrome b5, 51 are structurally and topologically equivalent to the globin fold. When these proteins have been superimposed, the heme irons are found to be less than 1.4 A separated and the heme normals are inclined by less than 9.5 degrees. Comparison of minimum base changes per codon between heme binding and NAD binding proteins are of the same order."} {"id": "PMID:181272", "title": "Do evolutionary changes in cytochrome c structure reflect functional adaptations?", "content": "Following the demonstration that the rate of evolutionary change in the amino acid sequences of cytochromes c of eukaryotic species was not constant either for a single line of phylogenetic descent during different evolutionary intervals or for separate lines of descent, the concept that neutral mutations account for the vast majority of the evolutionary variations could no longer be accepted. Previous studies had shown that all eukaryotic cytochromes c tested appeared to be functionally indistinguishable in their reaction with mitochondrial respiratory chain components. However, an examination of the kinetics at low ionic strength led to the discovery of a high affinity reaction of cytochrome c with cytochrome c oxidase that revealed large differences in activity between the cytochromes of the horse, baker's yeast and the protist Euglena. Observed Km values for this reaction of 10(-7) to 10(-8) M appear to represent actual dissociation constants, as demonstrated by direct binding studies of cytochrome c with purified cytochrome c oxidase. The high affinity reaction is sensitive to ionic strength and inhibited by ADP and ATP in the range of physiological concentrations, ATP being three times as effective as ADP. The possibility is discussed that this effect of ATP on cytochrome c binding to its oxidase could provide the basis of a mechanism for mitochondrial respiratory control. The demonstration of differences between cytochrome c of various species in this kinetic system opens the way to a systematic study of the possible evolutionary adaptations of cytochromes c to their oxidases.", "contents": "Do evolutionary changes in cytochrome c structure reflect functional adaptations? Following the demonstration that the rate of evolutionary change in the amino acid sequences of cytochromes c of eukaryotic species was not constant either for a single line of phylogenetic descent during different evolutionary intervals or for separate lines of descent, the concept that neutral mutations account for the vast majority of the evolutionary variations could no longer be accepted. Previous studies had shown that all eukaryotic cytochromes c tested appeared to be functionally indistinguishable in their reaction with mitochondrial respiratory chain components. However, an examination of the kinetics at low ionic strength led to the discovery of a high affinity reaction of cytochrome c with cytochrome c oxidase that revealed large differences in activity between the cytochromes of the horse, baker's yeast and the protist Euglena. Observed Km values for this reaction of 10(-7) to 10(-8) M appear to represent actual dissociation constants, as demonstrated by direct binding studies of cytochrome c with purified cytochrome c oxidase. The high affinity reaction is sensitive to ionic strength and inhibited by ADP and ATP in the range of physiological concentrations, ATP being three times as effective as ADP. The possibility is discussed that this effect of ATP on cytochrome c binding to its oxidase could provide the basis of a mechanism for mitochondrial respiratory control. The demonstration of differences between cytochrome c of various species in this kinetic system opens the way to a systematic study of the possible evolutionary adaptations of cytochromes c to their oxidases."} {"id": "PMID:181273", "title": "The origin and evolution of protein superfamilies.", "content": "The organization of proteins into superfamilies based primarily on their sequences is introduced: examples are given of the methods used to cluster the related sequences and to elucidate the evolutionary history of the corresponding genes within each superfamily. Within the framework of this organization, the amount of sequence information currently and potentially available in all living forms can be discussed. The 116 superfamilies already sampled reflect possibly 10% of the total number. There are related proteins from many species in all of these superfamilies, suggesting that the origin of a new superfamily is rare indeed. The proteins so far sequenced are so rigorously conserved by the evolutionary process that we would expect to recognize as related descendants of any protein found in the ancestral vertebrate. The evolutionary history of the thyrotropin-gonadotropin beta chain superfamily is discussed in detail as an example. Some proteins are so constrained in structure that related forms can be recognized in prokaryotes and eukaryotes. Evolution in these superfamilies can be traced back close to the origin of life itself. From the evolutionary tree of the c-type cytochromes the identity of the prokaryote types involved in the symbiotic origin of mitochondria and chloroplasts begins to emerge.", "contents": "The origin and evolution of protein superfamilies. The organization of proteins into superfamilies based primarily on their sequences is introduced: examples are given of the methods used to cluster the related sequences and to elucidate the evolutionary history of the corresponding genes within each superfamily. Within the framework of this organization, the amount of sequence information currently and potentially available in all living forms can be discussed. The 116 superfamilies already sampled reflect possibly 10% of the total number. There are related proteins from many species in all of these superfamilies, suggesting that the origin of a new superfamily is rare indeed. The proteins so far sequenced are so rigorously conserved by the evolutionary process that we would expect to recognize as related descendants of any protein found in the ancestral vertebrate. The evolutionary history of the thyrotropin-gonadotropin beta chain superfamily is discussed in detail as an example. Some proteins are so constrained in structure that related forms can be recognized in prokaryotes and eukaryotes. Evolution in these superfamilies can be traced back close to the origin of life itself. From the evolutionary tree of the c-type cytochromes the identity of the prokaryote types involved in the symbiotic origin of mitochondria and chloroplasts begins to emerge."} {"id": "PMID:181276", "title": "The mechanism of action of the copper intrauterine device.", "content": "The effects of copper ions on the binding of steroids to receptors revealed that the inhibitory effect of Cu++ was apparent at 10(-6)M, ANd the binding capacities decreased to 10% at 10(-2)M Cu++. The kinetic study demonstrated that Cu++ was a competitive inhibitor of steroid hormone-receptor binding (Ki divided by 2.7 X 10(-5)M to estrogen receptor; Ki divided by 5.1 X 10(-6)M to progesterone receptor). These results indicate that copper ions interfere at the steroid-binding site of receptor and that progesterone receptor is more affected by copper ions than is estrogen receptor. The sedimentation pattern showed the dissociation and aggregation of receptor macromolecules by copper. These phenomena may indicate the biologic inactivation of receptor. In fact, morphologically, progestational proliferation was severely inhibited and estrogenic action seemed to be inhibited. The Timm stain showed copper uptake by endometrial epithelium and superficial stromata. The copper content apparently increased in the cytoplasm of uteri bearing a copper intrauterine device, compared with controls. In vivo, the concentration of cytoplasmic copper was approximately 1.4 X 10(-6)M, which was obviously inhibitory to steroid hormone-receptor interaction. However, complete morphologic suppression of the progestational effect by copper cannot exclude the coexistence of some other mechanism in these phenomena.", "contents": "The mechanism of action of the copper intrauterine device. The effects of copper ions on the binding of steroids to receptors revealed that the inhibitory effect of Cu++ was apparent at 10(-6)M, ANd the binding capacities decreased to 10% at 10(-2)M Cu++. The kinetic study demonstrated that Cu++ was a competitive inhibitor of steroid hormone-receptor binding (Ki divided by 2.7 X 10(-5)M to estrogen receptor; Ki divided by 5.1 X 10(-6)M to progesterone receptor). These results indicate that copper ions interfere at the steroid-binding site of receptor and that progesterone receptor is more affected by copper ions than is estrogen receptor. The sedimentation pattern showed the dissociation and aggregation of receptor macromolecules by copper. These phenomena may indicate the biologic inactivation of receptor. In fact, morphologically, progestational proliferation was severely inhibited and estrogenic action seemed to be inhibited. The Timm stain showed copper uptake by endometrial epithelium and superficial stromata. The copper content apparently increased in the cytoplasm of uteri bearing a copper intrauterine device, compared with controls. In vivo, the concentration of cytoplasmic copper was approximately 1.4 X 10(-6)M, which was obviously inhibitory to steroid hormone-receptor interaction. However, complete morphologic suppression of the progestational effect by copper cannot exclude the coexistence of some other mechanism in these phenomena."} {"id": "PMID:181277", "title": "Gonadotropin binding sites in human postmenopausal ovaries.", "content": "Glucose-6-phosphate dehydrogenase (G6PD) activity and gonadotropin binding sites were localized within seven postmenopausal ovaries. G6PD was localized in the cells of cortical stroma and hilus using a histochemical technique for the reduction of the tetrazolium salt, Nitro-Blue tetrazolium. Gonadotropin binding sites were localized by autoradiography following incubation of ovarian sections with (125I-hLH) and 125I-labeled follicle-stimulating hormone (125I-hFSH) were identified in the cortical stroma and hilus cells. Since these cells contain G6PD and other enzymes necessary for steroidogenesis and also have the capacity to bind both hLH and hFSH, steroidogenesis in postmenopausal ovaries appears to be controlled by circulating gonadotropins. Blood vessels within postmenopausal ovaries also bound both gonadotropins, but 125I-hFSH binding was often more intense than 125I-hLH binding.", "contents": "Gonadotropin binding sites in human postmenopausal ovaries. Glucose-6-phosphate dehydrogenase (G6PD) activity and gonadotropin binding sites were localized within seven postmenopausal ovaries. G6PD was localized in the cells of cortical stroma and hilus using a histochemical technique for the reduction of the tetrazolium salt, Nitro-Blue tetrazolium. Gonadotropin binding sites were localized by autoradiography following incubation of ovarian sections with (125I-hLH) and 125I-labeled follicle-stimulating hormone (125I-hFSH) were identified in the cortical stroma and hilus cells. Since these cells contain G6PD and other enzymes necessary for steroidogenesis and also have the capacity to bind both hLH and hFSH, steroidogenesis in postmenopausal ovaries appears to be controlled by circulating gonadotropins. Blood vessels within postmenopausal ovaries also bound both gonadotropins, but 125I-hFSH binding was often more intense than 125I-hLH binding."} {"id": "PMID:181281", "title": "[Investigations of the morphology and the function of human Sertoli cells (author's transl)].", "content": "Ultrastructurally and enzyme histochemically two types of activities of Sertoli cells are to be proved. By means of closest membrane contact and intensive energetic changes of substances, the active cells participate largely in the ripening of spermatozoa. Steroid biosynthesis in Sertoli cells is possible according to their pattern of organelles and enzymes. The ultrastructure of Charcot-B\u00f6ttcher's crystalloids and the other characteristic inclusions in the cytoplasma of the Sertoli cells as well as implications to their function are described.", "contents": "[Investigations of the morphology and the function of human Sertoli cells (author's transl)]. Ultrastructurally and enzyme histochemically two types of activities of Sertoli cells are to be proved. By means of closest membrane contact and intensive energetic changes of substances, the active cells participate largely in the ripening of spermatozoa. Steroid biosynthesis in Sertoli cells is possible according to their pattern of organelles and enzymes. The ultrastructure of Charcot-B\u00f6ttcher's crystalloids and the other characteristic inclusions in the cytoplasma of the Sertoli cells as well as implications to their function are described."} {"id": "PMID:181282", "title": "Morphological and biochemical changes in the hepatic endoplasmic reticulum and golgi apparatus of male Xenopus laevis after induction of egg-yolk protein synthesis by oestradiol-17 beta.", "content": "This report describes morphological and biochemical changes accompanying oestrogen induced synthesis of the egg-yolk protein precursor, vitellogenin, in male Xenopus liver. Extensive proliferation of the rough and smooth endoplasmic reticulum and the Golgi apparatus occurs between 3 and 9 days after administration of oestradiol-17 beta. Subcellular fractionation showed that microsomal fractions have an increased number of ribosomes available for protein synthesis, hormone treatment enhances the in vitro protein synthetic capacity per unit of RNA; both in microsome and ribosome preparations. Polypeptides synthesized in vitro by ribosome preparations show an enrichment in serine content after hormone treatment and an increased proportion of ribosomes can be immunoprecipitated by antibodies directed against vitellogenin. Our data are consistent with the proposal that vitellogenin is synthesized on the ribosomes of the rough endoplasmic reticulum and processed and packaged for secretion in the smooth endoplasmic reticulum and Golgi apparatus. Response to hormonal induction of vitellogenin involves an early phase in which membrane proliferation occurs in order to increase the cellular capacity to synthesize, process and secrete large quantities of egg-yolk protein precursor.", "contents": "Morphological and biochemical changes in the hepatic endoplasmic reticulum and golgi apparatus of male Xenopus laevis after induction of egg-yolk protein synthesis by oestradiol-17 beta. This report describes morphological and biochemical changes accompanying oestrogen induced synthesis of the egg-yolk protein precursor, vitellogenin, in male Xenopus liver. Extensive proliferation of the rough and smooth endoplasmic reticulum and the Golgi apparatus occurs between 3 and 9 days after administration of oestradiol-17 beta. Subcellular fractionation showed that microsomal fractions have an increased number of ribosomes available for protein synthesis, hormone treatment enhances the in vitro protein synthetic capacity per unit of RNA; both in microsome and ribosome preparations. Polypeptides synthesized in vitro by ribosome preparations show an enrichment in serine content after hormone treatment and an increased proportion of ribosomes can be immunoprecipitated by antibodies directed against vitellogenin. Our data are consistent with the proposal that vitellogenin is synthesized on the ribosomes of the rough endoplasmic reticulum and processed and packaged for secretion in the smooth endoplasmic reticulum and Golgi apparatus. Response to hormonal induction of vitellogenin involves an early phase in which membrane proliferation occurs in order to increase the cellular capacity to synthesize, process and secrete large quantities of egg-yolk protein precursor."} {"id": "PMID:181283", "title": "Different effects of cycloheximide and chloramphenicol on corticosterone production by isolated rat adrenal cells.", "content": "Cycloheximide and chloramphenicol both inhibit the stimulating effect of adenocorticotropic hormone (ACTH) on adrenal steroid production. To test whether these inhibitors had andy effect on adrenal steroid production, independent fromthe mechanism of action of ACTH we investigated their effect on the conversion of 25-hydroxycholesterol into corticosterone in isolated rat adrenal cells. Cycloheximide, both in the absence and in the presence of ACTH, had no effect on this conversion. Chloramphenicol inhibited the conversion of 25-hydroxycholesterol into corticosterone whether ACTH has no direct efeect on the cholesterol side-chain cleaving system. The inhibition by chloramphenicol of the ACTH-stimulated steroid production is at least partly due to inhibition of one or more of the processes involved in the conversion of 25-hydroxycholesterol into corticosterone.", "contents": "Different effects of cycloheximide and chloramphenicol on corticosterone production by isolated rat adrenal cells. Cycloheximide and chloramphenicol both inhibit the stimulating effect of adenocorticotropic hormone (ACTH) on adrenal steroid production. To test whether these inhibitors had andy effect on adrenal steroid production, independent fromthe mechanism of action of ACTH we investigated their effect on the conversion of 25-hydroxycholesterol into corticosterone in isolated rat adrenal cells. Cycloheximide, both in the absence and in the presence of ACTH, had no effect on this conversion. Chloramphenicol inhibited the conversion of 25-hydroxycholesterol into corticosterone whether ACTH has no direct efeect on the cholesterol side-chain cleaving system. The inhibition by chloramphenicol of the ACTH-stimulated steroid production is at least partly due to inhibition of one or more of the processes involved in the conversion of 25-hydroxycholesterol into corticosterone."} {"id": "PMID:181285", "title": "Cryoprotein complexes and peripheral neuropathy in a patient with chronic active hepatitis.", "content": "A cryoprotein complex was isolated and characterized from a patient with chronic active hepatitis and a severe peripheral neuropathy. This cryoprotein was composed of IgM, IgG, and hepatitis B surface antigen (HBsAg) and had a concentration of approximately 36 mg per 100 ml of serum. Electron microscopic examination of the cryoprotein demonstrated aggregates of Dane particles in close association with the antigenically related tubular and spherical forms of HBsAg. HBsAg, IgM, and IgG were detected by immunofluorescent staining in the intima of small arteries and veins. The association of a high serum level of cryoprotein and deposition of the cryoprotein components in small blood vessels suggests a role for the cryoprotein in the pathogenesis of peripheral neuropathy in this patient with chronic active hepatitis.", "contents": "Cryoprotein complexes and peripheral neuropathy in a patient with chronic active hepatitis. A cryoprotein complex was isolated and characterized from a patient with chronic active hepatitis and a severe peripheral neuropathy. This cryoprotein was composed of IgM, IgG, and hepatitis B surface antigen (HBsAg) and had a concentration of approximately 36 mg per 100 ml of serum. Electron microscopic examination of the cryoprotein demonstrated aggregates of Dane particles in close association with the antigenically related tubular and spherical forms of HBsAg. HBsAg, IgM, and IgG were detected by immunofluorescent staining in the intima of small arteries and veins. The association of a high serum level of cryoprotein and deposition of the cryoprotein components in small blood vessels suggests a role for the cryoprotein in the pathogenesis of peripheral neuropathy in this patient with chronic active hepatitis."} {"id": "PMID:181286", "title": "Hepatitis in an adult caused by Herpes simplex virus type I.", "content": "Disseminated infection caused by Herpes simplex virus (HSV) type I is described in a previously healthy adult. The clinical course was characterized by progressive hepatic failure, fever, hypotension, atypical lymphocytosis, and disseminated intravascular coagulation. No skin lesions were present and the causal agent was not suspended premortem; however, HSV-I was isolated from autopsy liver, and characteristic histopathological lesions of herpes infection were observed in liver and esophagus.", "contents": "Hepatitis in an adult caused by Herpes simplex virus type I. Disseminated infection caused by Herpes simplex virus (HSV) type I is described in a previously healthy adult. The clinical course was characterized by progressive hepatic failure, fever, hypotension, atypical lymphocytosis, and disseminated intravascular coagulation. No skin lesions were present and the causal agent was not suspended premortem; however, HSV-I was isolated from autopsy liver, and characteristic histopathological lesions of herpes infection were observed in liver and esophagus."} {"id": "PMID:181296", "title": "Syndactyly and split hand.", "content": "Careful analysis of clinical and radiological features of both webbing of normal fingers and typical split hand, suggests that these two types of malformations should not be classified separately. Study of human embryos and experimental malformations of the apical ectodermal ridge, supplies a resonable explanation for the close relation between webbing of normal fingers and typical split hand.", "contents": "Syndactyly and split hand. Careful analysis of clinical and radiological features of both webbing of normal fingers and typical split hand, suggests that these two types of malformations should not be classified separately. Study of human embryos and experimental malformations of the apical ectodermal ridge, supplies a resonable explanation for the close relation between webbing of normal fingers and typical split hand."} {"id": "PMID:181297", "title": "Corticosteroid effect on eosinophils in vitro: ultrastructural studies.", "content": "The effect of corticosteroids, ultracortene and ACTH, on the eosinophilic cells of a patient with hypereosinophilic syndrome has been studied in vitro. Both drugs caused a marked decrease in the number of specific granules, a disappearance of their surrounding membrane and an almost complete destruction of their crystals. In addition, vacuolization of the cytoplasm, swelling of the mitochondria and distortion of their cristae were found. Incubation of the eosinophils with the antihistaminic drug mepyramine, did not produce ultrastructural alterations.", "contents": "Corticosteroid effect on eosinophils in vitro: ultrastructural studies. The effect of corticosteroids, ultracortene and ACTH, on the eosinophilic cells of a patient with hypereosinophilic syndrome has been studied in vitro. Both drugs caused a marked decrease in the number of specific granules, a disappearance of their surrounding membrane and an almost complete destruction of their crystals. In addition, vacuolization of the cytoplasm, swelling of the mitochondria and distortion of their cristae were found. Incubation of the eosinophils with the antihistaminic drug mepyramine, did not produce ultrastructural alterations."} {"id": "PMID:181298", "title": "Cytostatic treatment of polycythaemia rubra vera. Comparison of the effects of some cytostatics in 100 patients in a period of five years.", "content": "Experience with cytostatic treatment performed in patients with polycythaemia rubra vera is reviewed. The effectivity and side effects of the drugs applied are evaluated. Mannosulfan and mitobromitol were the drugs most sutiable for treatment. In certain special cases, 5-hydroxyurea was also satisfactory, while mitolactol was the least suitable.", "contents": "Cytostatic treatment of polycythaemia rubra vera. Comparison of the effects of some cytostatics in 100 patients in a period of five years. Experience with cytostatic treatment performed in patients with polycythaemia rubra vera is reviewed. The effectivity and side effects of the drugs applied are evaluated. Mannosulfan and mitobromitol were the drugs most sutiable for treatment. In certain special cases, 5-hydroxyurea was also satisfactory, while mitolactol was the least suitable."} {"id": "PMID:181299", "title": "Biochemical characterization and visualization of plasma membrane-DNA-protein complexes from Bacillus subtilis.", "content": "Subcellular fractions containing plasma membranes with bound DNA and associated proteins were isolated from two different cultures of Bacillus subtilis 168 growing exponentially at different rates. Differences in the contents of individual between the dissociated complexes, established electrophoretically, can be explained by dynamic binding of the proteins to DNA, resulting in a control of DNA, resulting in a control of DNA replication. Electron microphotographs of isolated complexes display, in addition to unit membranes, associated filamentous structures in different arragement. Patterns obtained after treating the complexes with nucleases suggest a polydeoxyribonucleotide character of the filamentous structures.", "contents": "Biochemical characterization and visualization of plasma membrane-DNA-protein complexes from Bacillus subtilis. Subcellular fractions containing plasma membranes with bound DNA and associated proteins were isolated from two different cultures of Bacillus subtilis 168 growing exponentially at different rates. Differences in the contents of individual between the dissociated complexes, established electrophoretically, can be explained by dynamic binding of the proteins to DNA, resulting in a control of DNA, resulting in a control of DNA replication. Electron microphotographs of isolated complexes display, in addition to unit membranes, associated filamentous structures in different arragement. Patterns obtained after treating the complexes with nucleases suggest a polydeoxyribonucleotide character of the filamentous structures."} {"id": "PMID:181302", "title": "Studies on the pituitary \"fettstoffwechselhormon\". VI. Preparation of two highly purified lipolytic active peptides from hog pituitary glands.", "content": "The preparation of two highly purified lipolytically active hog pituitary peptides, called P-LF II C and P-LF II D is described. The two peptides are free of other pituitary hormone activities. In isolated rat and porcine adipose tissue, both fractions are lipolytically much more active than every other lipolytic active pituitary peptide described to date. By fraction P-LF II D, the first pituitary peptide was isolated which has lipolytic activity in isolated rat adipose tissue than corticotropin, the lipolytically most active pituitary hormone known so far. On isolated porcine adipose tissue, fraction P-LF II D as well as P-LF II C showed without doubt higher activity than corticotropin.", "contents": "Studies on the pituitary \"fettstoffwechselhormon\". VI. Preparation of two highly purified lipolytic active peptides from hog pituitary glands. The preparation of two highly purified lipolytically active hog pituitary peptides, called P-LF II C and P-LF II D is described. The two peptides are free of other pituitary hormone activities. In isolated rat and porcine adipose tissue, both fractions are lipolytically much more active than every other lipolytic active pituitary peptide described to date. By fraction P-LF II D, the first pituitary peptide was isolated which has lipolytic activity in isolated rat adipose tissue than corticotropin, the lipolytically most active pituitary hormone known so far. On isolated porcine adipose tissue, fraction P-LF II D as well as P-LF II C showed without doubt higher activity than corticotropin."} {"id": "PMID:181303", "title": "The effects of estradiol administration of the hepatic activities of some enzymes of carbohydrate, amino acid and lipid metabolism in the immature pullet.", "content": "Two experiments were performed to examine the effects of intramuscular estradiol administration on the hepatic specific activities of some enzymes of lipid, carbohydrate and amino acid metabolism in the immature fowl. Estradiol increased the specific activities of the hepatic lipogenic enzymes, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP), but had no effects on the activities of the glycolytic, gluconeogenic and amino acid metabolising enzymes except for pyruvate kinase and glutamate dehydrogenase which were reduced in activity in both experiments. The results indicate that the estrogen-induced increase in hepatic lipid biosynthesis is due to a specific effect on lipid metabolism and not to a general increase in liver metabolism.", "contents": "The effects of estradiol administration of the hepatic activities of some enzymes of carbohydrate, amino acid and lipid metabolism in the immature pullet. Two experiments were performed to examine the effects of intramuscular estradiol administration on the hepatic specific activities of some enzymes of lipid, carbohydrate and amino acid metabolism in the immature fowl. Estradiol increased the specific activities of the hepatic lipogenic enzymes, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP), but had no effects on the activities of the glycolytic, gluconeogenic and amino acid metabolising enzymes except for pyruvate kinase and glutamate dehydrogenase which were reduced in activity in both experiments. The results indicate that the estrogen-induced increase in hepatic lipid biosynthesis is due to a specific effect on lipid metabolism and not to a general increase in liver metabolism."} {"id": "PMID:181304", "title": "Demonstration that cyclic adenosine 3',5'-monophosphate mediates the lipolytic action of parathyroid hormone.", "content": "Studies were carried out with rat epididymal fat pads first to compare the effects of the synthetic N-terminal 1-34 peptide of bovine parathyroid hormone and of the native hormone to determine whether this portion of the molecule is responsible for the lipolytic action of the hormone and second to determine whether this biologic action of parathyroid hormone is mediated by cyclic adenosine 3',5'-monophosphate. The N-terminal polypeptide was as effective as the native hormone in stimulating lipolysis in the concentration range between 10(-8) M and 10(-6) M. Parathyroid hormone stimulated lipolysis by isolated fat cells. The concentration of cyclic adenosine 3',5'-monophosphate in the fat pads was significantly increased by the hormone (10(-6)M). Lipolytic stimulation by parathyroid hormone (10(-6)M) was diminished by insulin (100 muU/ml) and prostaglandin E1 (1 mug/ml), both of which are known inhibitors of lipolysis. The findings indicate that the amino-terminal 1-34 peptide portion of parathyroid hormone is responsible for the lipolytic action and that this effect is mediated through cyclic adenosine 3',5'-monophosphate.", "contents": "Demonstration that cyclic adenosine 3',5'-monophosphate mediates the lipolytic action of parathyroid hormone. Studies were carried out with rat epididymal fat pads first to compare the effects of the synthetic N-terminal 1-34 peptide of bovine parathyroid hormone and of the native hormone to determine whether this portion of the molecule is responsible for the lipolytic action of the hormone and second to determine whether this biologic action of parathyroid hormone is mediated by cyclic adenosine 3',5'-monophosphate. The N-terminal polypeptide was as effective as the native hormone in stimulating lipolysis in the concentration range between 10(-8) M and 10(-6) M. Parathyroid hormone stimulated lipolysis by isolated fat cells. The concentration of cyclic adenosine 3',5'-monophosphate in the fat pads was significantly increased by the hormone (10(-6)M). Lipolytic stimulation by parathyroid hormone (10(-6)M) was diminished by insulin (100 muU/ml) and prostaglandin E1 (1 mug/ml), both of which are known inhibitors of lipolysis. The findings indicate that the amino-terminal 1-34 peptide portion of parathyroid hormone is responsible for the lipolytic action and that this effect is mediated through cyclic adenosine 3',5'-monophosphate."} {"id": "PMID:181300", "title": "[Virus infections of the respiratory tract of dogs].", "content": "Canine respiratory infections are reviewed with special reference to those caused by agents, other than distemper and canine infectious hepatitis viruses, but producing, both naturally and experimentally, the so-called distemper-like syndromes. The existence of canine infections caused by Adeno-Herpes-,Reo-, and Paramyxoviruses is reported, and for each of these agents the physicochemical characteristics, pathogenicity for dogs and other animal species, incidence and methods of dissemination are described. As regrads the prophylaxis of the individual infections that appear particularly widespread in kennels, the possible availability in the short or long term of immunizing preparations is indicated, along with the basic measures of hygiene for their control. The availability of immunizing preparations depends, firstly, on a more exact knowledge of the aetiological agents involved in canine respiratory conditions, and secondly, on a precise determination of the mechanisms by which the immune reactions are elicited. It is, however, obvious that the incidence of respiratory infections could be substantially reduced by the application of all the hygienic measures that can ensure a high environmental standard for the animals.", "contents": "[Virus infections of the respiratory tract of dogs]. Canine respiratory infections are reviewed with special reference to those caused by agents, other than distemper and canine infectious hepatitis viruses, but producing, both naturally and experimentally, the so-called distemper-like syndromes. The existence of canine infections caused by Adeno-Herpes-,Reo-, and Paramyxoviruses is reported, and for each of these agents the physicochemical characteristics, pathogenicity for dogs and other animal species, incidence and methods of dissemination are described. As regrads the prophylaxis of the individual infections that appear particularly widespread in kennels, the possible availability in the short or long term of immunizing preparations is indicated, along with the basic measures of hygiene for their control. The availability of immunizing preparations depends, firstly, on a more exact knowledge of the aetiological agents involved in canine respiratory conditions, and secondly, on a precise determination of the mechanisms by which the immune reactions are elicited. It is, however, obvious that the incidence of respiratory infections could be substantially reduced by the application of all the hygienic measures that can ensure a high environmental standard for the animals."} {"id": "PMID:181305", "title": "The role of calcium ion in epinephrine activation of lipolysis.", "content": "Adipocytes were prepared by collagenase digestion of rat epididymal adipose tissue and incubated for 5, 15 or 30 minutes in Krebs-Ringer bicarbonate buffer containing albumin (40 mg/ml), glucose (1 mg/ml) and epinephrine. Calcium ion was present in some incubations at concentration of 2.5 mM and omitted from others; media with no added calcium contained 1.0 mM EGTA thereby producing a final calcium concentration of less than 10(-7) M. Glycerol release and accumulation of cyclic AMP were measured. Basal lipolysis and cell cyclic AMP levels were increased slightly but not significantly when adipocytes were incubated in calcium free media. Lipolysis could be activated with epinephrine in the absence of calcium but the sensitivity of the lipolytic response was greatly reduced; however, the maximum lipolytic response to epinephrine was not decreased in calcium free media. Similarly, incubation of adipocytes in calcium free media resulted in decreased accumulation of cyclic AMP in response to epinephrine but only when sub-maximum concentrations of the catecholamine were present. Varying the extracellular calcium concentration showed that a concentration of at least 10(-5) M was optimal for epinephrine activation of lipolysis. These observations are considered in accord with the view that activation of adenylate cyclase is facilitated by calcium ion.", "contents": "The role of calcium ion in epinephrine activation of lipolysis. Adipocytes were prepared by collagenase digestion of rat epididymal adipose tissue and incubated for 5, 15 or 30 minutes in Krebs-Ringer bicarbonate buffer containing albumin (40 mg/ml), glucose (1 mg/ml) and epinephrine. Calcium ion was present in some incubations at concentration of 2.5 mM and omitted from others; media with no added calcium contained 1.0 mM EGTA thereby producing a final calcium concentration of less than 10(-7) M. Glycerol release and accumulation of cyclic AMP were measured. Basal lipolysis and cell cyclic AMP levels were increased slightly but not significantly when adipocytes were incubated in calcium free media. Lipolysis could be activated with epinephrine in the absence of calcium but the sensitivity of the lipolytic response was greatly reduced; however, the maximum lipolytic response to epinephrine was not decreased in calcium free media. Similarly, incubation of adipocytes in calcium free media resulted in decreased accumulation of cyclic AMP in response to epinephrine but only when sub-maximum concentrations of the catecholamine were present. Varying the extracellular calcium concentration showed that a concentration of at least 10(-5) M was optimal for epinephrine activation of lipolysis. These observations are considered in accord with the view that activation of adenylate cyclase is facilitated by calcium ion."} {"id": "PMID:181306", "title": "Cyclic AMP level of human thyroid cells in monolayer culture. TSH induced refractoriness to TSH action.", "content": "Thyroid cells from euthyroid patients with Graves' disease were cultured in a chemically defined medium. The cells preserved the ability to respond to TSH with 8-fold increase in cyclic AMP concentration. This cyclic AMP response to TSH was diminished by prior exposure of cells to TSH. The decrease in cyclic AMP response to TSH induced to TSH was reversible, was not associated with a similar decrease to cyclic AMP response to PGE1, and could not be attributed to increased phosphodiesterase activity or to decreased adenyl cyclase activity. The partial resistence to TSH stimulation of thyroid cells previously exposed to TSH may be due to changes in the TSH receptor, possibly caused by TSH itself.", "contents": "Cyclic AMP level of human thyroid cells in monolayer culture. TSH induced refractoriness to TSH action. Thyroid cells from euthyroid patients with Graves' disease were cultured in a chemically defined medium. The cells preserved the ability to respond to TSH with 8-fold increase in cyclic AMP concentration. This cyclic AMP response to TSH was diminished by prior exposure of cells to TSH. The decrease in cyclic AMP response to TSH induced to TSH was reversible, was not associated with a similar decrease to cyclic AMP response to PGE1, and could not be attributed to increased phosphodiesterase activity or to decreased adenyl cyclase activity. The partial resistence to TSH stimulation of thyroid cells previously exposed to TSH may be due to changes in the TSH receptor, possibly caused by TSH itself."} {"id": "PMID:181307", "title": "The different modes of action of thyrotropin and prostaglandin E1 on cyclic adenosine 3',5'-monophosphate synthesis in human thyroid, as studied by sequential stimulations.", "content": "PGE1 was equally effective in increasing 3H-cyclic AMP in normal and in toxic thyroids, whereas TSH was less effective but over a longer time in the toxic thyroids. Stimulation by a large second dose of TSH could not be elicited after prior stimulation by large doses of TSH. Similar results were obtained with regard to the effect of PGE1. However, stimulation by a large dose of PGE1 was still effective after the slices became refractory to TSH. Similarly, stimulation by a large dose of TSH was still effective after the slices became refractory to PGE1. It is suggested that the site and/or mode of action of TSH is quite different from that of PGE1.", "contents": "The different modes of action of thyrotropin and prostaglandin E1 on cyclic adenosine 3',5'-monophosphate synthesis in human thyroid, as studied by sequential stimulations. PGE1 was equally effective in increasing 3H-cyclic AMP in normal and in toxic thyroids, whereas TSH was less effective but over a longer time in the toxic thyroids. Stimulation by a large second dose of TSH could not be elicited after prior stimulation by large doses of TSH. Similar results were obtained with regard to the effect of PGE1. However, stimulation by a large dose of PGE1 was still effective after the slices became refractory to TSH. Similarly, stimulation by a large dose of TSH was still effective after the slices became refractory to PGE1. It is suggested that the site and/or mode of action of TSH is quite different from that of PGE1."} {"id": "PMID:181309", "title": "Pituitary and extrapituitary effects of somatostatin in normal man.", "content": "The effects of synthetic linear somatostatin on basal circulating levels on several pituitary and pancreatic hormones, and of glucose and free fatty acids (FFA) were studied in 6 normal men after an overnight fast. A priming intravenous infusion of 250 mug of somatostatin in 18 sec was followed by a constant infusion of 500 mug over a period of 60 min. A decrease in plasma values of GH, prolactin, TSH, insulin and glucagon and in blood glucose was observed during somatostatin infusion, while FFA levels increased progressively. Plasma IRI and blood glucose increased rapidly when the somatostatin infusion was stopped, while FFA decreased progressively; GH, prolactin, TSH and glucagon remained low as compared to basal levels for one hour after the end of the infusion, i.e. until the end of the experiment. A slight but significant increase of LH and ACTH was observed after the end of the infusion.", "contents": "Pituitary and extrapituitary effects of somatostatin in normal man. The effects of synthetic linear somatostatin on basal circulating levels on several pituitary and pancreatic hormones, and of glucose and free fatty acids (FFA) were studied in 6 normal men after an overnight fast. A priming intravenous infusion of 250 mug of somatostatin in 18 sec was followed by a constant infusion of 500 mug over a period of 60 min. A decrease in plasma values of GH, prolactin, TSH, insulin and glucagon and in blood glucose was observed during somatostatin infusion, while FFA levels increased progressively. Plasma IRI and blood glucose increased rapidly when the somatostatin infusion was stopped, while FFA decreased progressively; GH, prolactin, TSH and glucagon remained low as compared to basal levels for one hour after the end of the infusion, i.e. until the end of the experiment. A slight but significant increase of LH and ACTH was observed after the end of the infusion."} {"id": "PMID:181317", "title": "Variation of several erythrocyte enzymes in the Dayaks of Sarawak.", "content": "The Land and Sea Dayaks of Sarawak were surveyed for several erythrocyte enzymes. The gene frequency of 6PGDC in 132 Land Dayaks and 127 Sea Dayaks were 0.045 and 0.047, respectively. The gene frequency of PGM1-1 IN 285 Land Dayks and 240 Sea Dayaks were 0.716 and 0.779, respectively. The ADA2 gene frequency in 283 Land Dayaks and 188 Sea Dayaks were 0.154 and 0.090. ADA 5-1 was found once in the Land Dayaks and once in the Sea Dayaks. AK 2-1 was found once in 221 Sea Dayaks but not in any of 270 Land Dayaks. No PHI, LDH or CA variants were found among the Land or Sea Dayaks.", "contents": "Variation of several erythrocyte enzymes in the Dayaks of Sarawak. The Land and Sea Dayaks of Sarawak were surveyed for several erythrocyte enzymes. The gene frequency of 6PGDC in 132 Land Dayaks and 127 Sea Dayaks were 0.045 and 0.047, respectively. The gene frequency of PGM1-1 IN 285 Land Dayks and 240 Sea Dayaks were 0.716 and 0.779, respectively. The ADA2 gene frequency in 283 Land Dayaks and 188 Sea Dayaks were 0.154 and 0.090. ADA 5-1 was found once in the Land Dayaks and once in the Sea Dayaks. AK 2-1 was found once in 221 Sea Dayaks but not in any of 270 Land Dayaks. No PHI, LDH or CA variants were found among the Land or Sea Dayaks."} {"id": "PMID:181318", "title": "The formation of histotypic structures from monodisperse fetal rat lung cells cultured on a three-dimensional substrate.", "content": "Enzymatically dissociated lungs from rat fetuses at 19-days gestation yield single cells which reaggregate to form alveolar-like structures when cultured on gelatin sponge discs. These structures form within 2 days and have been maintained in vitro for as long as 6 weeks. They are composed primarily of type II pneumonocytes as characterized by large, lightly stained nuclei and cytoplasmic inclusion bodies. The lamellar structure of these inclusion bodies has been confirmed by electron microscopy. The dynamic formation of inclusion bodies is suggested by the presence of lamellar bodies in the extra-cellular space and the appearance of new inclusions in the cytoplasm of the type II pneumonocytes. The formation and long-term maintenance of histotypic lung structures in vitro provides a model system for the study of lung development and synthesis of surfactant by type II alveolar pneumonocytes.", "contents": "The formation of histotypic structures from monodisperse fetal rat lung cells cultured on a three-dimensional substrate. Enzymatically dissociated lungs from rat fetuses at 19-days gestation yield single cells which reaggregate to form alveolar-like structures when cultured on gelatin sponge discs. These structures form within 2 days and have been maintained in vitro for as long as 6 weeks. They are composed primarily of type II pneumonocytes as characterized by large, lightly stained nuclei and cytoplasmic inclusion bodies. The lamellar structure of these inclusion bodies has been confirmed by electron microscopy. The dynamic formation of inclusion bodies is suggested by the presence of lamellar bodies in the extra-cellular space and the appearance of new inclusions in the cytoplasm of the type II pneumonocytes. The formation and long-term maintenance of histotypic lung structures in vitro provides a model system for the study of lung development and synthesis of surfactant by type II alveolar pneumonocytes."} {"id": "PMID:181319", "title": "Suggestive evidence for both stimulatory and inhibitory domains on human lymphocytes, as indicated by phospholipid turnover studies with wheat germ agglutinin and other lectins.", "content": "Short term effects (1 hours or less) of various lectins on phospholipid turnover in human lymphocytes were studied. As expected, concanvalin A and phytohemagglutinin produced 1,5-4.0 fold increases in incorporation of 32PO4 radioactivity into phospholipids (primarily phosphatidylinositol). Wheat germ agglutinin, a nonmitogenic lectin, not only failed to produce a response but actually inhibited phospholipid turnover, both in the presence and absence of PHA or con A. Since wheat germ agglutinin did not appear to be cytotoxic, as defined by a failure to see changes in vital dye uptake, and other evidence from our laboratory indicates that this lectin also inhibits aminisobutyric acid transport and DNA synthesis in human lymphocytes we would tentatively interpret its negative action as indicating the existence of specific inhibitory domains on the cell surface.", "contents": "Suggestive evidence for both stimulatory and inhibitory domains on human lymphocytes, as indicated by phospholipid turnover studies with wheat germ agglutinin and other lectins. Short term effects (1 hours or less) of various lectins on phospholipid turnover in human lymphocytes were studied. As expected, concanvalin A and phytohemagglutinin produced 1,5-4.0 fold increases in incorporation of 32PO4 radioactivity into phospholipids (primarily phosphatidylinositol). Wheat germ agglutinin, a nonmitogenic lectin, not only failed to produce a response but actually inhibited phospholipid turnover, both in the presence and absence of PHA or con A. Since wheat germ agglutinin did not appear to be cytotoxic, as defined by a failure to see changes in vital dye uptake, and other evidence from our laboratory indicates that this lectin also inhibits aminisobutyric acid transport and DNA synthesis in human lymphocytes we would tentatively interpret its negative action as indicating the existence of specific inhibitory domains on the cell surface."} {"id": "PMID:181322", "title": "Immunological and biochemical studies of meningococcal C polysaccharides isolated by diethylaminoethyl chromatography.", "content": "Meningococcal C polysaccharides isolated from the broth supernatant of C1+ and C1- strains by a combination of Sepharose 4B and diethylaminoethyl-52 chromatography are antigenically identical to the group C antigen isolated by the Cetavlon procedure. Immunizations result in the induction of precipitating, hemagglutinating, and bactericidal antibodies in rabbits and sheep and hemagglutinating and bactericidal antibodies in rabbits and sheep and hemagglutinating and bactericidal antibodies in gerbils. Selective destruction of C1- polysaccharides with neuraminidase has demonstrated that these antibodies are directed against the C polysaccharide. Neuraminidase digestions of the C1- polysaccharides resulted in release of up to 84% of the antigen as N-acetylneuraminic acid. C1+ polysaccharides proved to be more resistant to neuraminidase, requiring greater concentrations of enzyme and longer intervals of exposure for digestion. Chemical analysis of the C1+ and C1- polysaccharides indicated that they contain less than 0.5% protein and less than 0.5% nucleic acid.", "contents": "Immunological and biochemical studies of meningococcal C polysaccharides isolated by diethylaminoethyl chromatography. Meningococcal C polysaccharides isolated from the broth supernatant of C1+ and C1- strains by a combination of Sepharose 4B and diethylaminoethyl-52 chromatography are antigenically identical to the group C antigen isolated by the Cetavlon procedure. Immunizations result in the induction of precipitating, hemagglutinating, and bactericidal antibodies in rabbits and sheep and hemagglutinating and bactericidal antibodies in rabbits and sheep and hemagglutinating and bactericidal antibodies in gerbils. Selective destruction of C1- polysaccharides with neuraminidase has demonstrated that these antibodies are directed against the C polysaccharide. Neuraminidase digestions of the C1- polysaccharides resulted in release of up to 84% of the antigen as N-acetylneuraminic acid. C1+ polysaccharides proved to be more resistant to neuraminidase, requiring greater concentrations of enzyme and longer intervals of exposure for digestion. Chemical analysis of the C1+ and C1- polysaccharides indicated that they contain less than 0.5% protein and less than 0.5% nucleic acid."} {"id": "PMID:181323", "title": "Thermal inactivation of rabies and other rhabdoviruses: stabilization by the chelating agent ethylenediaminetetraacetic acid at physiological temperatures.", "content": "Thermal inactivation of rabies and several other rhabdoviruses was studied using virus suspended in several different diluents. Rabies serogroup viruses were more stable than Kern Canyon or vesicular stomatitis viruses. Limited studies of two fish rhabdoviruses requiring low temperatures (less than 33 C) for replication indicated that they were not markedly more thermolabile than rabies virus. Bovine serum protein components in complex cell culture media stabilized virus at 56 C, but at temperatures of less than or equal to 37 C, sodium tris (hydroxymethyl)-aminomethane (NT) buffer containing ethylenediaminetetraacetic acid (EDTA) (NTE) was a much more efficient stabilizer of virus infectivity. Chelating agents EDTA and ethyleneglycol-bis-(beta-aminoethyl ether)tetraacetic acid were equally efficient in protection of rabies virus infectivity; the effect of each was lost when excess Ca2+ was added. Bovine serum in NT or NTE buffers produced a thermostabilizing effect at 37 C not provided by the same serum concentration in complex cell culture media. Bovine serum was more efficient than EDTA in stabilizing virus infectivity during repeated cycles of freezing and thawing.", "contents": "Thermal inactivation of rabies and other rhabdoviruses: stabilization by the chelating agent ethylenediaminetetraacetic acid at physiological temperatures. Thermal inactivation of rabies and several other rhabdoviruses was studied using virus suspended in several different diluents. Rabies serogroup viruses were more stable than Kern Canyon or vesicular stomatitis viruses. Limited studies of two fish rhabdoviruses requiring low temperatures (less than 33 C) for replication indicated that they were not markedly more thermolabile than rabies virus. Bovine serum protein components in complex cell culture media stabilized virus at 56 C, but at temperatures of less than or equal to 37 C, sodium tris (hydroxymethyl)-aminomethane (NT) buffer containing ethylenediaminetetraacetic acid (EDTA) (NTE) was a much more efficient stabilizer of virus infectivity. Chelating agents EDTA and ethyleneglycol-bis-(beta-aminoethyl ether)tetraacetic acid were equally efficient in protection of rabies virus infectivity; the effect of each was lost when excess Ca2+ was added. Bovine serum in NT or NTE buffers produced a thermostabilizing effect at 37 C not provided by the same serum concentration in complex cell culture media. Bovine serum was more efficient than EDTA in stabilizing virus infectivity during repeated cycles of freezing and thawing."} {"id": "PMID:181324", "title": "Effect of passive antibody on parainfluenza virus type 3 pneumonia in hamsters.", "content": "Both parainfluenza virus type 3 and respiratory syncytial virus may produce life-threatening pneumonia or bronchiolitis in infants less than 6 months old. Almost all infants in this age group possess passively acquired maternal antibodies to both viruses. It has been suggested that maternal antibodies may actually participate in the pathogenesis of these diseases in early infancy. This investigation examined the effect of moderate levels of passive antibody on the development of pneumonia in hamsters infected intranasally with parainfluenza virus type 3. The pneumonitis produced in this model was not enhanced by the presence of moderate levels of serum antibody to this virus. Furthermore, reinfection after an initial \"sensitizing\" infection under the cover of passive antibody did not result in a more severe pneumonitis. These studies do not support either of the two hypotheses that have been advanced to explain the pathogenesis of infections with respiratory syncytial virus in early infancy.", "contents": "Effect of passive antibody on parainfluenza virus type 3 pneumonia in hamsters. Both parainfluenza virus type 3 and respiratory syncytial virus may produce life-threatening pneumonia or bronchiolitis in infants less than 6 months old. Almost all infants in this age group possess passively acquired maternal antibodies to both viruses. It has been suggested that maternal antibodies may actually participate in the pathogenesis of these diseases in early infancy. This investigation examined the effect of moderate levels of passive antibody on the development of pneumonia in hamsters infected intranasally with parainfluenza virus type 3. The pneumonitis produced in this model was not enhanced by the presence of moderate levels of serum antibody to this virus. Furthermore, reinfection after an initial \"sensitizing\" infection under the cover of passive antibody did not result in a more severe pneumonitis. These studies do not support either of the two hypotheses that have been advanced to explain the pathogenesis of infections with respiratory syncytial virus in early infancy."} {"id": "PMID:181325", "title": "Stimulation of lymphocyte proliferation by killed mycobacteria and other bacterial species.", "content": "Killed mycobacteria and some mycobacterial fractions induced spleen cells from normal C3H mice to incorporate tritiated thymidine to a relatively high degree. Thymocytes under the same conditions were not activated. However, incorporation of thymidine was significantly increased when mixtures of thymus and spleen cells were cultured in the presence of the inducers. A similar activation of spleen cells was displayed in the presence of gram-positive and gram-negative non-mycobacterial species.", "contents": "Stimulation of lymphocyte proliferation by killed mycobacteria and other bacterial species. Killed mycobacteria and some mycobacterial fractions induced spleen cells from normal C3H mice to incorporate tritiated thymidine to a relatively high degree. Thymocytes under the same conditions were not activated. However, incorporation of thymidine was significantly increased when mixtures of thymus and spleen cells were cultured in the presence of the inducers. A similar activation of spleen cells was displayed in the presence of gram-positive and gram-negative non-mycobacterial species."} {"id": "PMID:181326", "title": "Influence of feed on onset of disease in subacute myelo-optico-neuropathy virus-infected mice.", "content": "An enriched feed, specially prepared to affect reproduction of mice, significantly suppressed the onset of disease in subacute myelo-optico-neuropathy virus-infected mice, whereas low-calorie feed enhanced the incidence of disease.", "contents": "Influence of feed on onset of disease in subacute myelo-optico-neuropathy virus-infected mice. An enriched feed, specially prepared to affect reproduction of mice, significantly suppressed the onset of disease in subacute myelo-optico-neuropathy virus-infected mice, whereas low-calorie feed enhanced the incidence of disease."} {"id": "PMID:181327", "title": "Rescue of vesicular stomatitis virus from homologous and heterologous interferon-induced resistance in human cell cultures by poxviruses.", "content": "In human cell cultures the ability of poxviruses to rescue vesicular stomatitis virus from human interferon-induced resistance was significantly more efficient than the ability to rescue it from simian interferon-induced resistance. The sensitivity of the poxvirus to interferon was not related to its ability to rescue vesicular stomatitis virus.", "contents": "Rescue of vesicular stomatitis virus from homologous and heterologous interferon-induced resistance in human cell cultures by poxviruses. In human cell cultures the ability of poxviruses to rescue vesicular stomatitis virus from human interferon-induced resistance was significantly more efficient than the ability to rescue it from simian interferon-induced resistance. The sensitivity of the poxvirus to interferon was not related to its ability to rescue vesicular stomatitis virus."} {"id": "PMID:181328", "title": "Lymphocyte transformation and interferon production in human mononuclear cell microcultures for assay of cellular immunity to herpes simplex virus.", "content": "Interferon production and transformation in response to herpes simplex virus antigen were studied in microcultures of human mononuclear cells. Mononuclear cells consisting of monocytes and both T and B lymphocytes were purified by Ficoll-Hypaque gradients. Lymphocytes, predominantly T with 5% B, were obtained by passage of buffy-coat cells through nylon fiber columns. For some experiments, autochthonous macrophages and column-purified lymphocytes were stimulated with herpesvirus antigen. The effect of specific antibody and cell concentration on reactivity is described. Crude and purified antigens were compared as cell culture stimulants. Significant differences in transformation and interferon were observed between donors with a history of herpes labialis and donors with no detectable antibody, both in cultures prepared by Ficoll-Hypaque gradients and by column purification of lymphocytes. Cultures from seronegative donors prepared by Ficoll-Hypaque gradients produced interferon but did not transform when stimulated by herpes simplex antigen. \"Immune\" interferon production, that is, type II as opposed to type I, occurred only with autochthonous macrophage and column-purified lymphocyte cultures. Interferon produced by Ficoll-Hypaque-purified mononuclear cultures was type I, and its production was unrelated to immune status. Similarly, column-purified lymphocytes responded to herpes simplex virus antigen with type I interferon if obtained from a seropositive donor.", "contents": "Lymphocyte transformation and interferon production in human mononuclear cell microcultures for assay of cellular immunity to herpes simplex virus. Interferon production and transformation in response to herpes simplex virus antigen were studied in microcultures of human mononuclear cells. Mononuclear cells consisting of monocytes and both T and B lymphocytes were purified by Ficoll-Hypaque gradients. Lymphocytes, predominantly T with 5% B, were obtained by passage of buffy-coat cells through nylon fiber columns. For some experiments, autochthonous macrophages and column-purified lymphocytes were stimulated with herpesvirus antigen. The effect of specific antibody and cell concentration on reactivity is described. Crude and purified antigens were compared as cell culture stimulants. Significant differences in transformation and interferon were observed between donors with a history of herpes labialis and donors with no detectable antibody, both in cultures prepared by Ficoll-Hypaque gradients and by column purification of lymphocytes. Cultures from seronegative donors prepared by Ficoll-Hypaque gradients produced interferon but did not transform when stimulated by herpes simplex antigen. \"Immune\" interferon production, that is, type II as opposed to type I, occurred only with autochthonous macrophage and column-purified lymphocyte cultures. Interferon produced by Ficoll-Hypaque-purified mononuclear cultures was type I, and its production was unrelated to immune status. Similarly, column-purified lymphocytes responded to herpes simplex virus antigen with type I interferon if obtained from a seropositive donor."} {"id": "PMID:181329", "title": "Severe hemorrhagic varicella with visceral involvement: virological and serological studies during treatment with cytosine arabinoside.", "content": "A boy 13 year-old suffered an extremely severe and prolonged attack of hemorrhagic chickenpox with visceral involvement, the diagnosis being confirmed by isolation of varicella-zoster-virus (VZV). There was no other compromising disease. All preceding vaccinations including two against smallpox had been uneventful. The severity of the attack could not be ascribed to any persistent cellular or humoral immunodeficiency. The patient developed a good antibody response. The course of serological reactions to VZV infection was studied extensively using the different techniques of complement fixation and immunofluorescence for IgG, IgM, and IgA antibodies. Therapy was conducted cautiously using cytosine arabinoside (Ara-C) between the 10th and 17th day of disease; the temperature fell and VZV multiplication ceased, strongly suggesting a beneficial influence on the patient, who recovered completely.", "contents": "Severe hemorrhagic varicella with visceral involvement: virological and serological studies during treatment with cytosine arabinoside. A boy 13 year-old suffered an extremely severe and prolonged attack of hemorrhagic chickenpox with visceral involvement, the diagnosis being confirmed by isolation of varicella-zoster-virus (VZV). There was no other compromising disease. All preceding vaccinations including two against smallpox had been uneventful. The severity of the attack could not be ascribed to any persistent cellular or humoral immunodeficiency. The patient developed a good antibody response. The course of serological reactions to VZV infection was studied extensively using the different techniques of complement fixation and immunofluorescence for IgG, IgM, and IgA antibodies. Therapy was conducted cautiously using cytosine arabinoside (Ara-C) between the 10th and 17th day of disease; the temperature fell and VZV multiplication ceased, strongly suggesting a beneficial influence on the patient, who recovered completely."} {"id": "PMID:181330", "title": "Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines.", "content": "Receptors for the third component of complement (C3) were demonstrated on the surface of established human lymphoid cell lines by a membrane fluorescence test with FITC- or TRITC-conjugated antibodies against human C3. Two-color fluorescence staining of EBV receptors and C3 receptors showed complete overlapping of green and red fluorescence. Capping of the EBV receptor induced co-capping of the C3 receptor and vice versa. There was neither overlapping nor co-capping when EBV or C3 receptors were examined in relation to Fc receptors, surface IgM or beta2 microglobulin. The kinetic pattern of EBV receptor capping was identical with the pattern of C3 receptor capping but differed from the pattern of IgM capping. These results suggest a close association between EBV and C3 receptors on the human B-lymphocyte.", "contents": "Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines. Receptors for the third component of complement (C3) were demonstrated on the surface of established human lymphoid cell lines by a membrane fluorescence test with FITC- or TRITC-conjugated antibodies against human C3. Two-color fluorescence staining of EBV receptors and C3 receptors showed complete overlapping of green and red fluorescence. Capping of the EBV receptor induced co-capping of the C3 receptor and vice versa. There was neither overlapping nor co-capping when EBV or C3 receptors were examined in relation to Fc receptors, surface IgM or beta2 microglobulin. The kinetic pattern of EBV receptor capping was identical with the pattern of C3 receptor capping but differed from the pattern of IgM capping. These results suggest a close association between EBV and C3 receptors on the human B-lymphocyte."} {"id": "PMID:181331", "title": "Detection of Epstein-Barr virus DNA in American Burkitt's lymphoma.", "content": "Twenty American patients with Burkitt's lymphoma (BL) were studied serologically and biochemically to detect an association with Epstein-Barr virus (EBV). A wide range of antibody reactivities was encountered. Five patients had serological profiles similar to those of African patients with BL: one and possibly two of these patients harbored EBV-DNA in their tumors. Fifteen patients had low or absent antibody to EBV: tumors from 10 of these patients lacked evidence of EBV-DNA. An unexplained association between elevated antibody (greater than or equal to 1:80) to EBV virus capsid antigen (VCA) and a favorable prognosis was noted in this series; this prognostic observation requires further substantiation. Thus, it appears that EBV-associated BL is inversely proportional to tumor endemicity. An etiological role for EBV in BL remains speculative.", "contents": "Detection of Epstein-Barr virus DNA in American Burkitt's lymphoma. Twenty American patients with Burkitt's lymphoma (BL) were studied serologically and biochemically to detect an association with Epstein-Barr virus (EBV). A wide range of antibody reactivities was encountered. Five patients had serological profiles similar to those of African patients with BL: one and possibly two of these patients harbored EBV-DNA in their tumors. Fifteen patients had low or absent antibody to EBV: tumors from 10 of these patients lacked evidence of EBV-DNA. An unexplained association between elevated antibody (greater than or equal to 1:80) to EBV virus capsid antigen (VCA) and a favorable prognosis was noted in this series; this prognostic observation requires further substantiation. Thus, it appears that EBV-associated BL is inversely proportional to tumor endemicity. An etiological role for EBV in BL remains speculative."} {"id": "PMID:181332", "title": "Phenotypic mixing of vesicular stomatitis virus and D-type oncornavirus.", "content": "After mixed infection of cells with vesicular stomatitis virus (VSV, thermolabile mutant tl 17) and oncornavirus type D, phenotypically mixed virions are formed containing the VSV genome and oncornavirus and VSV envelope. The virions are thermostable and have serologic characteristics of both viruses.", "contents": "Phenotypic mixing of vesicular stomatitis virus and D-type oncornavirus. After mixed infection of cells with vesicular stomatitis virus (VSV, thermolabile mutant tl 17) and oncornavirus type D, phenotypically mixed virions are formed containing the VSV genome and oncornavirus and VSV envelope. The virions are thermostable and have serologic characteristics of both viruses."} {"id": "PMID:181333", "title": "Epstein-Barr virus: experimental infection of Callithrix jacchus marmosets.", "content": "Eight common marmoset monkeys (Callithrix jacchus) were inoculated with about 10(4) transforming units of B95-8 virus; seven of the marmosets died 50-111 days post inoculation and all seven showed microscopic and/or macroscopic lesions compatible with a diagnosis of lymphoproliferative disease. Low levels of anti-VCA antibodies were detected in plasma from six marmosets. Attempts failed to establish continuous EBV-carrying lymphoblastoid cell cultures by cultivation in vitro of circulating lymphocytes or minced lymphoid tissues obtained at necropsy.", "contents": "Epstein-Barr virus: experimental infection of Callithrix jacchus marmosets. Eight common marmoset monkeys (Callithrix jacchus) were inoculated with about 10(4) transforming units of B95-8 virus; seven of the marmosets died 50-111 days post inoculation and all seven showed microscopic and/or macroscopic lesions compatible with a diagnosis of lymphoproliferative disease. Low levels of anti-VCA antibodies were detected in plasma from six marmosets. Attempts failed to establish continuous EBV-carrying lymphoblastoid cell cultures by cultivation in vitro of circulating lymphocytes or minced lymphoid tissues obtained at necropsy."} {"id": "PMID:181334", "title": "A biochemical approach to the study of the transmission of mouse mammary tumor viruses in mouse strains RIII and C3H.", "content": "Mouse mammary tumor virus (MMTV) proviral sequences were detected in the cellular DNA of mammary tumors and livers of RIII and C3H mice by molecular hybridization with radioactively labelled MMTV 60-70S RNA or tritiated MMTV complementary DNA (cDNA). By means of DNA:DNA reassociation kinetics, the DNA of the mammary tumor cells of these two mouse strains were found to contain more MMTV proviral sequences than the DNA of liver cells of these same tumor-bearing mice. Evidence is also presented that the DNA of the liver cells lacks a part (approximately 25%) of the MMTV proviral sequences found in the mammary tumor cells of these mouse strains. The relationship of the extra MMTV proviral sequences found in mammary tumor cells to the early mammary tumor-igenesis seen in these mouse strains is discussed.", "contents": "A biochemical approach to the study of the transmission of mouse mammary tumor viruses in mouse strains RIII and C3H. Mouse mammary tumor virus (MMTV) proviral sequences were detected in the cellular DNA of mammary tumors and livers of RIII and C3H mice by molecular hybridization with radioactively labelled MMTV 60-70S RNA or tritiated MMTV complementary DNA (cDNA). By means of DNA:DNA reassociation kinetics, the DNA of the mammary tumor cells of these two mouse strains were found to contain more MMTV proviral sequences than the DNA of liver cells of these same tumor-bearing mice. Evidence is also presented that the DNA of the liver cells lacks a part (approximately 25%) of the MMTV proviral sequences found in the mammary tumor cells of these mouse strains. The relationship of the extra MMTV proviral sequences found in mammary tumor cells to the early mammary tumor-igenesis seen in these mouse strains is discussed."} {"id": "PMID:181335", "title": "Anti-EBV antibody titers in non-Hodgkin lymphomas.", "content": "Antibody titers to Epstein-Barr virus (EBV)-related antigens, i.e. viral capsid antigen (VCA), the D and R components of the early antigen (EA) complex and the EBV-associated nuclear antigen (EBNA), were determined in a series of 86 patients with non-Hodgkin lymphomas and in 150 matched control subjects. The lymphoma patients belonged to four histological groups: diffuse, nodular, hyperbasophilic malignant lymphoma (HML) and unclassified. The EBV-related serological data were compared to the incidence of antibodies to other herpes viruses, i.e. cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella zoster virus (VZV), and correlated with immune disorders, which are particularly frequent in the HML type of lymphoma. The results revealed a significantly higher incidence of anti-EA-D titers in lymphoma patients and slight but significant increases in the geometric mean anti-VCA titers in the HML and unclassified group of patients. These elevated anti-EBV titers in patients were not associated with an increase in titres of antibodies to other herpes viruses. They did not correlate with the signs of immune deficiency observed or with the incidence of auto-antibodies.", "contents": "Anti-EBV antibody titers in non-Hodgkin lymphomas. Antibody titers to Epstein-Barr virus (EBV)-related antigens, i.e. viral capsid antigen (VCA), the D and R components of the early antigen (EA) complex and the EBV-associated nuclear antigen (EBNA), were determined in a series of 86 patients with non-Hodgkin lymphomas and in 150 matched control subjects. The lymphoma patients belonged to four histological groups: diffuse, nodular, hyperbasophilic malignant lymphoma (HML) and unclassified. The EBV-related serological data were compared to the incidence of antibodies to other herpes viruses, i.e. cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella zoster virus (VZV), and correlated with immune disorders, which are particularly frequent in the HML type of lymphoma. The results revealed a significantly higher incidence of anti-EA-D titers in lymphoma patients and slight but significant increases in the geometric mean anti-VCA titers in the HML and unclassified group of patients. These elevated anti-EBV titers in patients were not associated with an increase in titres of antibodies to other herpes viruses. They did not correlate with the signs of immune deficiency observed or with the incidence of auto-antibodies."} {"id": "PMID:181336", "title": "Production of lymphoid tumors in hamsters by direct implantation of normal human peripheral and umbilical cord leukocytes.", "content": "Peripheral leukocytes from Epstein-Barr virus (EBV)-seropositive or seronegative normal adults, or human umbilical cord leukocytes infected or not infected with EBV, were directly transplanted into 50 newborn hamsters treated with anti-lymphocyte serum. Lymphoid tumors were produced after a latent period of 10-25 days in 39 animals: 8 of 14 recipients of seropositive donor leukocytes, 2 of 2 recipients of seronegative donor leukocytes, 13 of 15 recipients of EBV-infected cord leukocytes, and 16 of 19 recipients of non-infected cord leukocytes. EBV-determined nuclear antigen-positive human lymphoblastoid cell lines were established in vitro from tumors produced with seropositive donor leukocytes or EBV-infected cord leukocytes but not from tumors produced with seronegative donor leukocytes or non-infected cord leukocytes. The results indicate that EBV is not a prerequisite for in vivo production of tumors but necessary for in vitro establishment of lymphoblastoid cell lines from such tumors.", "contents": "Production of lymphoid tumors in hamsters by direct implantation of normal human peripheral and umbilical cord leukocytes. Peripheral leukocytes from Epstein-Barr virus (EBV)-seropositive or seronegative normal adults, or human umbilical cord leukocytes infected or not infected with EBV, were directly transplanted into 50 newborn hamsters treated with anti-lymphocyte serum. Lymphoid tumors were produced after a latent period of 10-25 days in 39 animals: 8 of 14 recipients of seropositive donor leukocytes, 2 of 2 recipients of seronegative donor leukocytes, 13 of 15 recipients of EBV-infected cord leukocytes, and 16 of 19 recipients of non-infected cord leukocytes. EBV-determined nuclear antigen-positive human lymphoblastoid cell lines were established in vitro from tumors produced with seropositive donor leukocytes or EBV-infected cord leukocytes but not from tumors produced with seronegative donor leukocytes or non-infected cord leukocytes. The results indicate that EBV is not a prerequisite for in vivo production of tumors but necessary for in vitro establishment of lymphoblastoid cell lines from such tumors."} {"id": "PMID:181337", "title": "A quantitative analysis of the susceptibility of human leukocytes to transformation by Epstein-Barr virus.", "content": "Susceptibility of lymphocyte-enriched cell fractions isolated from human umbilical cord blood and adult peripheral blood to transformation by the B95-8 strain of Epstein-Barr virus (EBV) was investigated quantitatively. Minimum multiplicity of input of virus (50% transforming dose) per cell (MOI) necessary to induce maximum level transformation of cord cells ranged from 0.02 to 0.2. The frequency of initially transformed cells (fraction of transformable cells) in the cord cell samples from two different individuals was estimated to be 2.6 to 6.2%. In this system, the appearance of cells positive for EBV-associated nuclear antigen (EBNA) paralleled the growth curve of transformed cells. About 70% of the latter were EBNA-positive. In adult cell preparations from two individuals, 1.8 and 0.03%, respectively, of the cells were transformable indicating larger individual variations in sensitivity to EBV than in cord cells. The EBV susceptibility was also determined by the transforming efficiency (TE) expressed as the negative log of the virus dilution which induces transformation in 50% of cell cultures infected at an MOI of 0.2. From the TE value, a minimum MOI which induces transfromation could be calculated. Also by this test it was shown that the EBV susceptibility of adult cells was not only lower but also much more variable between individuals than that of cord cells. There was no correlation between the susceptibility of cells and the titer of anti-EBV antibody in donors' sera. In cultures of mixed cord cells and adult cells known to have low EBV susceptibility, the minimum MOI increased in proportion to the amount of adult cells.", "contents": "A quantitative analysis of the susceptibility of human leukocytes to transformation by Epstein-Barr virus. Susceptibility of lymphocyte-enriched cell fractions isolated from human umbilical cord blood and adult peripheral blood to transformation by the B95-8 strain of Epstein-Barr virus (EBV) was investigated quantitatively. Minimum multiplicity of input of virus (50% transforming dose) per cell (MOI) necessary to induce maximum level transformation of cord cells ranged from 0.02 to 0.2. The frequency of initially transformed cells (fraction of transformable cells) in the cord cell samples from two different individuals was estimated to be 2.6 to 6.2%. In this system, the appearance of cells positive for EBV-associated nuclear antigen (EBNA) paralleled the growth curve of transformed cells. About 70% of the latter were EBNA-positive. In adult cell preparations from two individuals, 1.8 and 0.03%, respectively, of the cells were transformable indicating larger individual variations in sensitivity to EBV than in cord cells. The EBV susceptibility was also determined by the transforming efficiency (TE) expressed as the negative log of the virus dilution which induces transformation in 50% of cell cultures infected at an MOI of 0.2. From the TE value, a minimum MOI which induces transfromation could be calculated. Also by this test it was shown that the EBV susceptibility of adult cells was not only lower but also much more variable between individuals than that of cord cells. There was no correlation between the susceptibility of cells and the titer of anti-EBV antibody in donors' sera. In cultures of mixed cord cells and adult cells known to have low EBV susceptibility, the minimum MOI increased in proportion to the amount of adult cells."} {"id": "PMID:181338", "title": "Independent regulation of two types of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in mammalian cells.", "content": "Aryl hydrocarbon (benzo(a)pyrene) hydroxylase induced by dibutyryl cyclic AMP (dcAMP), plus aminophylline (AHH I) can be ditsinguished from the hydroxylase induced by benz (a) anthracene (AHH II) by its lower Km for benzo (a) pyrene. Treatment with the combination of benzo (a) anthracene and dcAMP plus aminophylline induced both AHH I and AHH II activities. After optimal induction of AHH II activity by benz (a) anthracene, the addition of dcAMP plus aminophylline gave an induction of AHH I. Although AHH I activity declined to an almost basal level 24 h after treatment with dcAMP plus aminophylline, the addition of benz (a) anthracene prevented this decline. Inducibility by dcAMP plus aminophylline or by benz (a) anthracene varied in different cell lines. Some cell lines were induced by both substances, with a higher induction by benz (a) anthracene, while other lines were inducible only by benz (a) anthracene, and a third cell type was not inducible by either. Selection for resistance to benzo (a) pyrene of a cell line inducible by both compounds resulted in a fourth cell type which was more inducible by dcAMP plus aminophylline than by benz (a) anthracene. The results suggest that there is an independent regulation of hydroxylase AHH I and AHH II and that the induction of these two enzyme activities is determined by different genetic controls.", "contents": "Independent regulation of two types of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in mammalian cells. Aryl hydrocarbon (benzo(a)pyrene) hydroxylase induced by dibutyryl cyclic AMP (dcAMP), plus aminophylline (AHH I) can be ditsinguished from the hydroxylase induced by benz (a) anthracene (AHH II) by its lower Km for benzo (a) pyrene. Treatment with the combination of benzo (a) anthracene and dcAMP plus aminophylline induced both AHH I and AHH II activities. After optimal induction of AHH II activity by benz (a) anthracene, the addition of dcAMP plus aminophylline gave an induction of AHH I. Although AHH I activity declined to an almost basal level 24 h after treatment with dcAMP plus aminophylline, the addition of benz (a) anthracene prevented this decline. Inducibility by dcAMP plus aminophylline or by benz (a) anthracene varied in different cell lines. Some cell lines were induced by both substances, with a higher induction by benz (a) anthracene, while other lines were inducible only by benz (a) anthracene, and a third cell type was not inducible by either. Selection for resistance to benzo (a) pyrene of a cell line inducible by both compounds resulted in a fourth cell type which was more inducible by dcAMP plus aminophylline than by benz (a) anthracene. The results suggest that there is an independent regulation of hydroxylase AHH I and AHH II and that the induction of these two enzyme activities is determined by different genetic controls."} {"id": "PMID:181339", "title": "Meeting the psychosocial needs of pacemaker patients.", "content": "A review of the literature concerning patients who have received permanently implanted cardiac pacemakers indicates that a substantial number of these patients experience difficulties in adjusting to their medical condition. Common feelings among these patients are anxiety and depression. It is suggested that difficulties often arise from the patient's misconceptions about the pacemaker and inadequate psychosocial support. To assist such patients in their adjustment, the Pacemaker Support Program was developed to provide psychosocial counseling and pacemaker education from the preoperative phase through to the outpatient pacemaker follow-up clinic phase. In the year of the program's operation a marked decline in adjustment problems has been observed, the program has been readily integrated into the hospital routine, and it has been enthusiastically accepted by both the hospital staff and the patients.", "contents": "Meeting the psychosocial needs of pacemaker patients. A review of the literature concerning patients who have received permanently implanted cardiac pacemakers indicates that a substantial number of these patients experience difficulties in adjusting to their medical condition. Common feelings among these patients are anxiety and depression. It is suggested that difficulties often arise from the patient's misconceptions about the pacemaker and inadequate psychosocial support. To assist such patients in their adjustment, the Pacemaker Support Program was developed to provide psychosocial counseling and pacemaker education from the preoperative phase through to the outpatient pacemaker follow-up clinic phase. In the year of the program's operation a marked decline in adjustment problems has been observed, the program has been readily integrated into the hospital routine, and it has been enthusiastically accepted by both the hospital staff and the patients."} {"id": "PMID:181340", "title": "The role of the psychiatric consultant in the treatment of burned patients.", "content": "Two cases of seriously burned patients are presented which differ in initial psychiatric presentation and subsequent course. In each case, the role of the psychiatric consultant is described. The role includes direct evaluative and psychotherapeutic contact with the patient and liaison with the surgical and nursing staff. This dual approach is necessary for a consistent rehabilitative effort, particularly in hospitals that do not have a psychiatric liaison team.", "contents": "The role of the psychiatric consultant in the treatment of burned patients. Two cases of seriously burned patients are presented which differ in initial psychiatric presentation and subsequent course. In each case, the role of the psychiatric consultant is described. The role includes direct evaluative and psychotherapeutic contact with the patient and liaison with the surgical and nursing staff. This dual approach is necessary for a consistent rehabilitative effort, particularly in hospitals that do not have a psychiatric liaison team."} {"id": "PMID:181343", "title": "An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection.", "content": "An in vitro line was derived from an American Burkitt lymphoma, designated Ra No. 1, which produced malignant tumors when inoculated into thymus-deficient nude mice. The cells have B-lymphocyte characteristics, with surface-associated mu and kappa chains and Epstein-Barr virus (EBV) receptors, and can be readily infected with EBV in vitro. B95-8 virus induced EBV-determined nuclear antigen (EBNA) but not early antigen (EA) in Ra No. 1 cells, whereas P3HR-1 virus induced both EBNA and EA, but the EA level was much lower than in the prototype Raji strain, EBNA and EA levels were comparable in Ra No. 1 and in the previously established, EBV-infection-sensitive BJA-B lymphoma. The two lines differed, however, because BJA-B could be converted into a permanent EBV-carrying line by the B95-8 but not by the P3HR-1 virus strain, whereas Ra No. 1 could be converted by the P3HR-1 virus. This demonstrates that different B-lymphocyte-derived lymphoma lines can vary with regard to the restrictive control they can exert on the same virus strain. Furthermore, virus strains vary in their sensitivity to the restrictions of the same host cell. Permanent EBV conversion of the Ra No. 1 cell did not appear to change the cellular controls, as judged by the unchanged sensitivity of the cell to viral antigen (EA, viral capsid antigen) induction by P3HR-1 virus superinfection.", "contents": "An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. An in vitro line was derived from an American Burkitt lymphoma, designated Ra No. 1, which produced malignant tumors when inoculated into thymus-deficient nude mice. The cells have B-lymphocyte characteristics, with surface-associated mu and kappa chains and Epstein-Barr virus (EBV) receptors, and can be readily infected with EBV in vitro. B95-8 virus induced EBV-determined nuclear antigen (EBNA) but not early antigen (EA) in Ra No. 1 cells, whereas P3HR-1 virus induced both EBNA and EA, but the EA level was much lower than in the prototype Raji strain, EBNA and EA levels were comparable in Ra No. 1 and in the previously established, EBV-infection-sensitive BJA-B lymphoma. The two lines differed, however, because BJA-B could be converted into a permanent EBV-carrying line by the B95-8 but not by the P3HR-1 virus strain, whereas Ra No. 1 could be converted by the P3HR-1 virus. This demonstrates that different B-lymphocyte-derived lymphoma lines can vary with regard to the restrictive control they can exert on the same virus strain. Furthermore, virus strains vary in their sensitivity to the restrictions of the same host cell. Permanent EBV conversion of the Ra No. 1 cell did not appear to change the cellular controls, as judged by the unchanged sensitivity of the cell to viral antigen (EA, viral capsid antigen) induction by P3HR-1 virus superinfection."} {"id": "PMID:181344", "title": "Morphological changes in chick embryo cell cultures induced by avian leukosis viruses.", "content": "Morphological alterations were observed after 5-15 serial passages of cells infected with three different strains of avian leukosis virus: OK 10, an A subgroup virus isolated from a natural infection; RAV-1, an established laboratory strain of the A subgroup, and RAV-2, a laboratory strain of the B subgroup. The infected cells had a prolonged lifespan of approximately 28 passages, compared to 14 passages for control cells. However, the altered cells had none of the attributes of transformed cells, such as growth in soft agar, loss of contact inhibition, tumor formation in chickens, or loss of fibroblast surface antigen. Therefore, we refer to the changes as conversion rather than transformation. The morphological changes differed depending upon the subgroup of the inducing virus. Cells converted with the A subgroup viruses were uniformly epitheloid whereas cells converted with the B subgroup virus were less uniform in size and shape. We speculate that an event similar to conversion may take place in vivo and contribute to the oncogenicity of leukosis viruses.", "contents": "Morphological changes in chick embryo cell cultures induced by avian leukosis viruses. Morphological alterations were observed after 5-15 serial passages of cells infected with three different strains of avian leukosis virus: OK 10, an A subgroup virus isolated from a natural infection; RAV-1, an established laboratory strain of the A subgroup, and RAV-2, a laboratory strain of the B subgroup. The infected cells had a prolonged lifespan of approximately 28 passages, compared to 14 passages for control cells. However, the altered cells had none of the attributes of transformed cells, such as growth in soft agar, loss of contact inhibition, tumor formation in chickens, or loss of fibroblast surface antigen. Therefore, we refer to the changes as conversion rather than transformation. The morphological changes differed depending upon the subgroup of the inducing virus. Cells converted with the A subgroup viruses were uniformly epitheloid whereas cells converted with the B subgroup virus were less uniform in size and shape. We speculate that an event similar to conversion may take place in vivo and contribute to the oncogenicity of leukosis viruses."} {"id": "PMID:181345", "title": "Cytomegalovirus infection of human lung epithelial cells in vitro.", "content": "Human lung epithelial cells were productively infected with human cytomegalovirus in vitro. Infectious virus was released up to 8 weeks postinfection. The cells retained their morphological characteristics throughout the period of observation, while simultaneously bearing all the features typical of cytomegalovirus infection.", "contents": "Cytomegalovirus infection of human lung epithelial cells in vitro. Human lung epithelial cells were productively infected with human cytomegalovirus in vitro. Infectious virus was released up to 8 weeks postinfection. The cells retained their morphological characteristics throughout the period of observation, while simultaneously bearing all the features typical of cytomegalovirus infection."} {"id": "PMID:181346", "title": "Preliminary studies on an unusual poxvirus of the western grey squirrel (Sciurus griseus griseus) of North America.", "content": "Particles of a poxvirus found in Californian western grey squirrels have overall dimensions indistinguishable from those of the poxviruses of the genera Orthopoxvirus and Leporipoxvirus, but have surface structures somewhat reminiscent of virions of members of the genus Parapoxvirus. Extracts of tissues infected with the squirrel poxvirus cross-react in gel-diffusion tests with extracts of tissues infected with Californian myxoma virus, but not with a similar preparation infected with a South American strain of myxoma virus.", "contents": "Preliminary studies on an unusual poxvirus of the western grey squirrel (Sciurus griseus griseus) of North America. Particles of a poxvirus found in Californian western grey squirrels have overall dimensions indistinguishable from those of the poxviruses of the genera Orthopoxvirus and Leporipoxvirus, but have surface structures somewhat reminiscent of virions of members of the genus Parapoxvirus. Extracts of tissues infected with the squirrel poxvirus cross-react in gel-diffusion tests with extracts of tissues infected with Californian myxoma virus, but not with a similar preparation infected with a South American strain of myxoma virus."} {"id": "PMID:181347", "title": "Infectivity of Rous sarcoma cell DNA: comparison of two techniques of transfection assay.", "content": "A DNA extracted from a clone of chicken cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D(SR-RSV-D), was assayed for infectivity by means of DEAE-dextran and calcium techniques. The calcium technique like the previously described DEAE-dextran procedure gave rise to viruses in transfection assays with both native and denatured (S1 nuclease susceptible) DNAs. The efficiency of these transfection techniques with native DNA was compared and found to be about the same provided that with the calcium technique carrier DNA was used to complement DNA concentrations lower than 2.5 mug/ml.", "contents": "Infectivity of Rous sarcoma cell DNA: comparison of two techniques of transfection assay. A DNA extracted from a clone of chicken cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D(SR-RSV-D), was assayed for infectivity by means of DEAE-dextran and calcium techniques. The calcium technique like the previously described DEAE-dextran procedure gave rise to viruses in transfection assays with both native and denatured (S1 nuclease susceptible) DNAs. The efficiency of these transfection techniques with native DNA was compared and found to be about the same provided that with the calcium technique carrier DNA was used to complement DNA concentrations lower than 2.5 mug/ml."} {"id": "PMID:181348", "title": "Effect of thyroidectomy and in vivo administration of triiodothyronine on DNA synthesis in isolated mitochondria.", "content": "The experimental conditions were studied which allow hormonal levels to affect the incorporation of labelled deoxyribonucleosides triphosphates (dNTP's) into mitochondrial DNA by isolated liver mitochondria, obtained either from thyroidectomized young male rats (T) or from animals of the same age thyroidectomized and then treated with triiodothyronine (T + T3). It was demonstrated that: (a) extramitochondrial DNA, on which extramitochondrial DNA polymerase may act, was absent; (b) the permeability to dNTP's, the thymidine kinase activity, the energy supply, and the nuclease activities were unaffected by hormonal conditions; (c) the bacterial contaminations contribute for only 1% to incorporation. The characterization of incorporation product showed that: (a) such product was indeed DNA, as it was DNase-degradable for about 90%; (b) the labelled DNA was indeed mitochondrial DNA, as a 10 minutes preincubation with acriflavine or ethydium bromide (Eth. Br.) inhibited the synthesis by 90%.", "contents": "Effect of thyroidectomy and in vivo administration of triiodothyronine on DNA synthesis in isolated mitochondria. The experimental conditions were studied which allow hormonal levels to affect the incorporation of labelled deoxyribonucleosides triphosphates (dNTP's) into mitochondrial DNA by isolated liver mitochondria, obtained either from thyroidectomized young male rats (T) or from animals of the same age thyroidectomized and then treated with triiodothyronine (T + T3). It was demonstrated that: (a) extramitochondrial DNA, on which extramitochondrial DNA polymerase may act, was absent; (b) the permeability to dNTP's, the thymidine kinase activity, the energy supply, and the nuclease activities were unaffected by hormonal conditions; (c) the bacterial contaminations contribute for only 1% to incorporation. The characterization of incorporation product showed that: (a) such product was indeed DNA, as it was DNase-degradable for about 90%; (b) the labelled DNA was indeed mitochondrial DNA, as a 10 minutes preincubation with acriflavine or ethydium bromide (Eth. Br.) inhibited the synthesis by 90%."} {"id": "PMID:181351", "title": "Characteristics of immunity induced by neuraminidase-treated lymphosarcoma cells in C3H (MTV+) and C3H (MTV-) mice.", "content": "The immunogenicity of 6C3HED lymphosarcoma ascites tumor cells was greatly enhanced upon treatment with Vibrio cholerae neuraminidase. As a result, mammary tumor virus (MTV)-free C3H mice which had been repeatedly immunized with the treated cells resisted a challenge of 10(6) untreated viable cells inoculated i.p., whereas all control animals died after receiving less than 10 lymphosarcoma tumor cells. In contrast, there was no increase in the refractoriness to challenge when MTV-infected C3H mice were immunized. Incubation of 6C3HED lymphosarcoma cells with serum of splenic lymphocytes from the immunized MTV-free C3H mice neutralized their tumorigenicity and protected recipient MTV-free and MTV-infected C3H mice against the disease. As shown by the 51Cr microcytotoxicity assay, the complement-dependent cytotoxic antibody titer reached 1,024; 29% of the target cells were lysed by lymphocytes obtained from immune MTV-free C3H mice. When the immune lymphocytes were pretreated with anti-theta serum they lost their ability to neutralize the tumorigenicity of the lymphosarcoma, failed to be stimulated by the T cell mitogens, phytohemagglutinin and concanavalin A, and failed to achieve cytolysis of the lymphosarcoma target cells in vitro. These observations establish the central role of the theta-antigen-bearing immune lymphocytes in cell-mediated immunity in this system. Failure of the immune system in the immunized MTV-infected C3H mice to cope with the challenging lymphosarcoma, even at low cell numbers, was reflected, not in the absence of humoral response, but in the relatively low level of cell-mediated immunity. This was manifested in both the neutralization and in the vitro cell-mediated immunity assays. This apparent immunological deficiency observed in the MTV-infected C3H mice could be countered by the transfer of lymphocytes from MTV-free C3H mice immunized with neuraminidase-treated 6C3HED lymphosarcoma cells. The recipient MTV-infected C3H mice then rejected a subsequent challenge with lymphosarcoma tumor grafts.", "contents": "Characteristics of immunity induced by neuraminidase-treated lymphosarcoma cells in C3H (MTV+) and C3H (MTV-) mice. The immunogenicity of 6C3HED lymphosarcoma ascites tumor cells was greatly enhanced upon treatment with Vibrio cholerae neuraminidase. As a result, mammary tumor virus (MTV)-free C3H mice which had been repeatedly immunized with the treated cells resisted a challenge of 10(6) untreated viable cells inoculated i.p., whereas all control animals died after receiving less than 10 lymphosarcoma tumor cells. In contrast, there was no increase in the refractoriness to challenge when MTV-infected C3H mice were immunized. Incubation of 6C3HED lymphosarcoma cells with serum of splenic lymphocytes from the immunized MTV-free C3H mice neutralized their tumorigenicity and protected recipient MTV-free and MTV-infected C3H mice against the disease. As shown by the 51Cr microcytotoxicity assay, the complement-dependent cytotoxic antibody titer reached 1,024; 29% of the target cells were lysed by lymphocytes obtained from immune MTV-free C3H mice. When the immune lymphocytes were pretreated with anti-theta serum they lost their ability to neutralize the tumorigenicity of the lymphosarcoma, failed to be stimulated by the T cell mitogens, phytohemagglutinin and concanavalin A, and failed to achieve cytolysis of the lymphosarcoma target cells in vitro. These observations establish the central role of the theta-antigen-bearing immune lymphocytes in cell-mediated immunity in this system. Failure of the immune system in the immunized MTV-infected C3H mice to cope with the challenging lymphosarcoma, even at low cell numbers, was reflected, not in the absence of humoral response, but in the relatively low level of cell-mediated immunity. This was manifested in both the neutralization and in the vitro cell-mediated immunity assays. This apparent immunological deficiency observed in the MTV-infected C3H mice could be countered by the transfer of lymphocytes from MTV-free C3H mice immunized with neuraminidase-treated 6C3HED lymphosarcoma cells. The recipient MTV-infected C3H mice then rejected a subsequent challenge with lymphosarcoma tumor grafts."} {"id": "PMID:181356", "title": "Structural investigation of the antibiotic ristomycin A. Synthesis of ristobiose and ristotriose.", "content": "Proof is given by synthesis confirming the structure of ristobiose as 2-O-alpha-D-mannopyranosyl-D-glucose (IV) and ristotriose as O-alpha-L-rhamnopyranosyl (1 leads to 6)-O-[alpha-D-mannopyranosyl (1 leads to 2)]-D-glucose (X) which are obtained from ristomycin A upon mild acid hydrolysis. Both oligosaccharides, IV and X, have been detected for the first time as the components of an antibiotic.", "contents": "Structural investigation of the antibiotic ristomycin A. Synthesis of ristobiose and ristotriose. Proof is given by synthesis confirming the structure of ristobiose as 2-O-alpha-D-mannopyranosyl-D-glucose (IV) and ristotriose as O-alpha-L-rhamnopyranosyl (1 leads to 6)-O-[alpha-D-mannopyranosyl (1 leads to 2)]-D-glucose (X) which are obtained from ristomycin A upon mild acid hydrolysis. Both oligosaccharides, IV and X, have been detected for the first time as the components of an antibiotic."} {"id": "PMID:181352", "title": "Complete regression of a guinea pig hepatocarcinoma by immunotherapy with \"tumor-immune\" RNA or antibody to fibrin fragment E.", "content": "Two novel immunotherapeutic regimens were developed for a uniformly lethal, intradermally growing transplantable ascites variant (line 10) of a diethylnitrosamine-induced hepatoma in strain 2 guinea pigs. In an apparently tumor-specific immunotherapy model, 32 guinea pigs were cured by the injection into the tumor area, five or seven days after tumor challenge, of syngeneic or xenogeneic RNA extracts obtained from lymphoid tissues of line 10-immune strain 2 guinea pigs or rhesus monkeys, as part of a total regimen which included syngeneic nonsensitive peritoneal exudate cells injected prior to, and tumor-specific antigen injected after, the RNA. In another immunotherapy model, not tumor-specific, 18 strain 2 guinea pigs were cured by the injection into the tumor area, 6 and 16 days after tumor challenge, of antibody specific for fibrin fragment E (FFE), an essential component in the formation of a fibrin matrix considered to be important in tumor development. When therapy was delayed to 12 days in the RNA test system, or to 16 days in the anti-FFE test system, complete abrogation of the tumors did not occur. The long-term survival of the 50 successfully treated animals and their immunity to further tumor challenge indicated that both immunotherapeutic procedures had systemic effects. To test this further, line 10 cells were injected intradermally simultaneously at two sites and only one site was treated. When the one tumor location was treated with anti-FFE, complete regression of the treated tumor and a 30% retardation in the development of the untreated tumor were observed. When this tumor location was treated with the RNA regimen, complete regression of the tumors occurred at both the treated and the untreated sites. Optimal conditions for both immunotherapeutic models and their combination have yet to be establshed. Nonetheless, both immunotherapeutic regimens were more effective than any other immunotherapy thus far reported for this tumor, including the use of BCG or its derivatives.", "contents": "Complete regression of a guinea pig hepatocarcinoma by immunotherapy with \"tumor-immune\" RNA or antibody to fibrin fragment E. Two novel immunotherapeutic regimens were developed for a uniformly lethal, intradermally growing transplantable ascites variant (line 10) of a diethylnitrosamine-induced hepatoma in strain 2 guinea pigs. In an apparently tumor-specific immunotherapy model, 32 guinea pigs were cured by the injection into the tumor area, five or seven days after tumor challenge, of syngeneic or xenogeneic RNA extracts obtained from lymphoid tissues of line 10-immune strain 2 guinea pigs or rhesus monkeys, as part of a total regimen which included syngeneic nonsensitive peritoneal exudate cells injected prior to, and tumor-specific antigen injected after, the RNA. In another immunotherapy model, not tumor-specific, 18 strain 2 guinea pigs were cured by the injection into the tumor area, 6 and 16 days after tumor challenge, of antibody specific for fibrin fragment E (FFE), an essential component in the formation of a fibrin matrix considered to be important in tumor development. When therapy was delayed to 12 days in the RNA test system, or to 16 days in the anti-FFE test system, complete abrogation of the tumors did not occur. The long-term survival of the 50 successfully treated animals and their immunity to further tumor challenge indicated that both immunotherapeutic procedures had systemic effects. To test this further, line 10 cells were injected intradermally simultaneously at two sites and only one site was treated. When the one tumor location was treated with anti-FFE, complete regression of the treated tumor and a 30% retardation in the development of the untreated tumor were observed. When this tumor location was treated with the RNA regimen, complete regression of the tumors occurred at both the treated and the untreated sites. Optimal conditions for both immunotherapeutic models and their combination have yet to be establshed. Nonetheless, both immunotherapeutic regimens were more effective than any other immunotherapy thus far reported for this tumor, including the use of BCG or its derivatives."} {"id": "PMID:181353", "title": "Interactions between lymphocytes and C-type oncornaviruses in mice.", "content": "Several aspects of C-type oncornavirus-lymphocyte interactions in the mouse are reviewed: 1) immunological abnormalities induced by C-type viruses, particularly immunosuppression and autoimmunity; 2) activation or amplification of endogenous C-type viruses during immunological reactions; and 3) the immune responses to these endogenous oncornaviruses. A unifying hypothesis is proposed to relate various interactions between lymphocytes and C-type oncornaviruses.", "contents": "Interactions between lymphocytes and C-type oncornaviruses in mice. Several aspects of C-type oncornavirus-lymphocyte interactions in the mouse are reviewed: 1) immunological abnormalities induced by C-type viruses, particularly immunosuppression and autoimmunity; 2) activation or amplification of endogenous C-type viruses during immunological reactions; and 3) the immune responses to these endogenous oncornaviruses. A unifying hypothesis is proposed to relate various interactions between lymphocytes and C-type oncornaviruses."} {"id": "PMID:181359", "title": "Pathway of thiamine pyrophosphate synthesis in Micrococcus denitrificans.", "content": "The pathway of thiamine pyrophosphate (TPP) biosynthesis, which is formed either from exogeneously added thiamine or from the pyrimidine and thiazole moieties of thiamine, in Micrococcus denitrificans was investigated. The following indirect evidence shows that thiamine pyrophosphokinase (EC 2.7.6.2) catalyzes the synthesis of TPP from thiamine: (i) [35S]thiamine incubated with cells of this microorganism was detected in the form of [35S]thiamine; (ii) thiamine gave a much faster rate of TPP synthesis than thiamine monophosphate (TMP) when determined with the extracts; and (iii) a partially purified preparation of the extracts can use thiamine, but not TMP, as the substrate. The activities of the four enzymes involved in TMP synthesis from pyrimidine and thiazole moieties of thiamine were detected in the extracts of M. denitrificans. The extracts contained a high activity of the phosphatase, probably specific for TMP. After M. denitrificans cells were grown on a minimal medium containing 3 mM adenosine, which causes derepression of de novo thiamine biosynthesis in Escherichia coli, the activities of the four enzymes involved with TMP synthesis, the TMP phosphatase, and the thiamine pyrophosphokinase were enhanced two- to threefold. These results indicate that TPP is synthesized directly from thiamine without forming TMP as an intermediate and that de novo synthesis of TPP from the pyrimidine and thiazole moieties involves the formation of TMP, followed by hydrolysis to thiamine, which is then converted to TPP directly. Thus, the pathway of TPP synthesis from TMP synthesized de novo in M. denitrificans is different from that found in E. coli, in which TMP synthesized de novo is converted directly to TPP without producing thiamine.", "contents": "Pathway of thiamine pyrophosphate synthesis in Micrococcus denitrificans. The pathway of thiamine pyrophosphate (TPP) biosynthesis, which is formed either from exogeneously added thiamine or from the pyrimidine and thiazole moieties of thiamine, in Micrococcus denitrificans was investigated. The following indirect evidence shows that thiamine pyrophosphokinase (EC 2.7.6.2) catalyzes the synthesis of TPP from thiamine: (i) [35S]thiamine incubated with cells of this microorganism was detected in the form of [35S]thiamine; (ii) thiamine gave a much faster rate of TPP synthesis than thiamine monophosphate (TMP) when determined with the extracts; and (iii) a partially purified preparation of the extracts can use thiamine, but not TMP, as the substrate. The activities of the four enzymes involved in TMP synthesis from pyrimidine and thiazole moieties of thiamine were detected in the extracts of M. denitrificans. The extracts contained a high activity of the phosphatase, probably specific for TMP. After M. denitrificans cells were grown on a minimal medium containing 3 mM adenosine, which causes derepression of de novo thiamine biosynthesis in Escherichia coli, the activities of the four enzymes involved with TMP synthesis, the TMP phosphatase, and the thiamine pyrophosphokinase were enhanced two- to threefold. These results indicate that TPP is synthesized directly from thiamine without forming TMP as an intermediate and that de novo synthesis of TPP from the pyrimidine and thiazole moieties involves the formation of TMP, followed by hydrolysis to thiamine, which is then converted to TPP directly. Thus, the pathway of TPP synthesis from TMP synthesized de novo in M. denitrificans is different from that found in E. coli, in which TMP synthesized de novo is converted directly to TPP without producing thiamine."} {"id": "PMID:181360", "title": "Variation in levels of enzymes related to energy metabolism in alternative developmental pathways of Blastocladiella emersonii.", "content": "The activities of phosphofructokinase (PFK), fructose diphosphatase (FDP), nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP)-linked isocitrate dehydrogenases (IDHNAD, IDHNADP), two NAD-linked glutamate dehydrogenases (GDH1, GDH2), and isocitrate lyase were studied during the development of the two phenotypes, ordinary colorless and resistant sporangia (OC and RS plants), of water mold Blastocladiella emersonii in synchronized liquid cultures. The OC plants had a generation time of about 12 h, whereas the RS plants required 3.5 days to reach maturity. All the enzymes were present throughout the development of both phenotypes. In zoospores, PFK, FDP, and GDH2 were localized in the cytosol. The IDHNADP activity was distributed with two-thirds in the soluble and one-third in the particulate fraction. GDH1 and IDHNAD showed the same distribution and were predominantly present in the particulate fraction, presumably in the mitochondria. Isocitrate lyase was found in the particulate fraction. The enzyme levels changed considerably during development. FDP and IDHNADP varied in a parallel manner. Similarly, the three enzymes PFK, IDHNAD and GDH1 showed parallel variations. The activity patterns for all enzymes were different for the OC and RS pathways. Isocitrate lyase exhibited the largest changes in activity during development. Thus, during OC plant formation, its activity decreased by a factor of 20. GDH2 varied similarly to PFK and IDHNADP during OC plant development, whereas it behaved like isocitrate lyase during RS plant development. The ratios between anabolic and catabolic enzymes were higher in mature plants than in zoospores and higher in RS plants than in OC plants. The results indicate that the variations in the enzyme levels are secondary to the critical changes involved in the transition from one developmental pathway to the other.", "contents": "Variation in levels of enzymes related to energy metabolism in alternative developmental pathways of Blastocladiella emersonii. The activities of phosphofructokinase (PFK), fructose diphosphatase (FDP), nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP)-linked isocitrate dehydrogenases (IDHNAD, IDHNADP), two NAD-linked glutamate dehydrogenases (GDH1, GDH2), and isocitrate lyase were studied during the development of the two phenotypes, ordinary colorless and resistant sporangia (OC and RS plants), of water mold Blastocladiella emersonii in synchronized liquid cultures. The OC plants had a generation time of about 12 h, whereas the RS plants required 3.5 days to reach maturity. All the enzymes were present throughout the development of both phenotypes. In zoospores, PFK, FDP, and GDH2 were localized in the cytosol. The IDHNADP activity was distributed with two-thirds in the soluble and one-third in the particulate fraction. GDH1 and IDHNAD showed the same distribution and were predominantly present in the particulate fraction, presumably in the mitochondria. Isocitrate lyase was found in the particulate fraction. The enzyme levels changed considerably during development. FDP and IDHNADP varied in a parallel manner. Similarly, the three enzymes PFK, IDHNAD and GDH1 showed parallel variations. The activity patterns for all enzymes were different for the OC and RS pathways. Isocitrate lyase exhibited the largest changes in activity during development. Thus, during OC plant formation, its activity decreased by a factor of 20. GDH2 varied similarly to PFK and IDHNADP during OC plant development, whereas it behaved like isocitrate lyase during RS plant development. The ratios between anabolic and catabolic enzymes were higher in mature plants than in zoospores and higher in RS plants than in OC plants. The results indicate that the variations in the enzyme levels are secondary to the critical changes involved in the transition from one developmental pathway to the other."} {"id": "PMID:181361", "title": "Suppression of polarity of insertion mutations in the gal operon and N mutations in bacteriophage lambda.", "content": "Bacterial mutations (psuA and psu) known for their ability to suppress the polarity on nonsense mutations are shown to suppress the polarity of certain insertion mutations in the gal operon. The short insertion, IS1 (800 nucleotide pairs), is about 15 to 50% suppressed, whereas longer insertions, IS2 (1,400 nucleotide pairs), and IS3 (1,200 nucleotide pairs), are not. Some of the polarity suppressor mutations (psu-1, psu-2, and psu-3) are at least partially permissive for N-gene mutations (N7 and N53) of bacteriophage lambda, suggesting a relationship between natural and mutational polar signals. That this relationship may be complex is indicated by the fact that other suppressor mutations, effective in suppressing nonsense or insertion polarity, fail entirely to permit the growth of lambda N mutants.", "contents": "Suppression of polarity of insertion mutations in the gal operon and N mutations in bacteriophage lambda. Bacterial mutations (psuA and psu) known for their ability to suppress the polarity on nonsense mutations are shown to suppress the polarity of certain insertion mutations in the gal operon. The short insertion, IS1 (800 nucleotide pairs), is about 15 to 50% suppressed, whereas longer insertions, IS2 (1,400 nucleotide pairs), and IS3 (1,200 nucleotide pairs), are not. Some of the polarity suppressor mutations (psu-1, psu-2, and psu-3) are at least partially permissive for N-gene mutations (N7 and N53) of bacteriophage lambda, suggesting a relationship between natural and mutational polar signals. That this relationship may be complex is indicated by the fact that other suppressor mutations, effective in suppressing nonsense or insertion polarity, fail entirely to permit the growth of lambda N mutants."} {"id": "PMID:181362", "title": "Mutations affecting catabolite repression of the L-arabinose regulon in Escherichia coli B/r.", "content": "Expression of the L-arabinose regulon in Escherichia coli B/r requires, among other things, cyclic adenosine-3', 5'-monophosphate (cAMP) and the cAMP receptor protein (CRP). Mutants deficient in adenyl cyclase (cya-), the enzyme which synthesizes cAMP, or CRP (crp-) are unable to utilize a variety of carbohydrates, including L-arabinose. Ara+ revertants of a cya-crp- strain were isolated on 0.2% minimal L-arabinose plates, conditions which require the entire ara regulon to be activated in the absence of cAMP and CRP. Evidence from genetic and physiological studies is consistent with placing these mutations in the araC regulatory gene. Deletion mapping with one mutant localized the site within either araO or araC, and complementation tests indicated the mutants acted trans to confer the ability to utilize L-arabinose in a cya-crp- genetic background. Since genetic analysis supports the conclusion, that the mutant sites are in the araC regulatory gene, the mutants were designated araCi, indicating a mutation in the regulatory gene affecting the cAMP-CRP requirement. Physiological analysis of one mutant, araCi1, illustrates the trans-acting nature of the mutation. In a cya-crp- genetic background, araCi1 promoted synthesis of both isomerase, a product of the araBAD operon, and permease, a product of the araE operon. Isomerase and permease levels in araCi1 cya+ crp+ were hyperinducible, and the sensitivity of each to cAMP was altered. Two models are presented that show the possible mutational lesion in the araCi strains.", "contents": "Mutations affecting catabolite repression of the L-arabinose regulon in Escherichia coli B/r. Expression of the L-arabinose regulon in Escherichia coli B/r requires, among other things, cyclic adenosine-3', 5'-monophosphate (cAMP) and the cAMP receptor protein (CRP). Mutants deficient in adenyl cyclase (cya-), the enzyme which synthesizes cAMP, or CRP (crp-) are unable to utilize a variety of carbohydrates, including L-arabinose. Ara+ revertants of a cya-crp- strain were isolated on 0.2% minimal L-arabinose plates, conditions which require the entire ara regulon to be activated in the absence of cAMP and CRP. Evidence from genetic and physiological studies is consistent with placing these mutations in the araC regulatory gene. Deletion mapping with one mutant localized the site within either araO or araC, and complementation tests indicated the mutants acted trans to confer the ability to utilize L-arabinose in a cya-crp- genetic background. Since genetic analysis supports the conclusion, that the mutant sites are in the araC regulatory gene, the mutants were designated araCi, indicating a mutation in the regulatory gene affecting the cAMP-CRP requirement. Physiological analysis of one mutant, araCi1, illustrates the trans-acting nature of the mutation. In a cya-crp- genetic background, araCi1 promoted synthesis of both isomerase, a product of the araBAD operon, and permease, a product of the araE operon. Isomerase and permease levels in araCi1 cya+ crp+ were hyperinducible, and the sensitivity of each to cAMP was altered. Two models are presented that show the possible mutational lesion in the araCi strains."} {"id": "PMID:181363", "title": "Effect of araC gene product on catabolite repression in the L-arabinose regulon.", "content": "The araCi protein differs in stability from araC+ protein and alters the concentration of cyclic adenosine-3', 5'-monophosphate required to maximally stimulate L-arabinose isomerase synthesis in an in vitro protein-synthesizing system.", "contents": "Effect of araC gene product on catabolite repression in the L-arabinose regulon. The araCi protein differs in stability from araC+ protein and alters the concentration of cyclic adenosine-3', 5'-monophosphate required to maximally stimulate L-arabinose isomerase synthesis in an in vitro protein-synthesizing system."} {"id": "PMID:181364", "title": "Disruption of the fucose pathway as a consequence of genetic adaptation to propanediol as a carbon source in Escherichia coli.", "content": "In Escherichia coli, L-fucose is dissimilated via an inducible pathway mediated by L-fucose permease, L-fucose isomerase, L-fucose kinase, and L-fuculose 1-phosphate aldolase. The last enzyme cleaves the six-carbon substrate into dihydroxyacetone phosphate and L-lactaldehyde. Aerobically, lactaldehyde is oxidized to L-lactate by a nicotinamide adenine dinucleotide (NAD)-linked dehydrogenase. Anaerobically, lactaldehyde is reduced by an NADH-COUPLED REDUCTASE TO L-1,2-propanediol, which is lost into the medium irretrievably, even when oxygen is subsequently introduced. Propanediol excretion is thus the end result of a dismutation that permits further anaerobic metabolism of dihydroxy-acetone phosphate. A mutant selected for its ability to grow aerobically on propanediol as a carbon and energy source was reported to produce lactaldehyde reductase constitutively and at high levels, even aerobically. Under the new situation, this enzyme serves as a propanediol dehydrogenase. It was also reported that the mutant had lost the ability to grow on fucose. In the present study, it is shown that in wild-type cells the full synthesis of lactaldehyde dehydrogenase requires the presence of both molecular oxygen and a small molecule effector, and the full synthesis of lactaldehyde reductase requires anaerobiosis and the presence of a small molecule effector. The failure of mutant cells to grow on fucose reflects the impairment of a regulatory element in the fucose system that prevents the induction of the permease, the isomerase, and the kinase. The aldolase, on the other hand, is constitutively synthesized. Three independent fucose-utilizing revertants of the mutant all produce the permease, the isomerase, the kinase, as well as the aldolase, constitutively. These strains grow less well than the parental mutant on propanediol.", "contents": "Disruption of the fucose pathway as a consequence of genetic adaptation to propanediol as a carbon source in Escherichia coli. In Escherichia coli, L-fucose is dissimilated via an inducible pathway mediated by L-fucose permease, L-fucose isomerase, L-fucose kinase, and L-fuculose 1-phosphate aldolase. The last enzyme cleaves the six-carbon substrate into dihydroxyacetone phosphate and L-lactaldehyde. Aerobically, lactaldehyde is oxidized to L-lactate by a nicotinamide adenine dinucleotide (NAD)-linked dehydrogenase. Anaerobically, lactaldehyde is reduced by an NADH-COUPLED REDUCTASE TO L-1,2-propanediol, which is lost into the medium irretrievably, even when oxygen is subsequently introduced. Propanediol excretion is thus the end result of a dismutation that permits further anaerobic metabolism of dihydroxy-acetone phosphate. A mutant selected for its ability to grow aerobically on propanediol as a carbon and energy source was reported to produce lactaldehyde reductase constitutively and at high levels, even aerobically. Under the new situation, this enzyme serves as a propanediol dehydrogenase. It was also reported that the mutant had lost the ability to grow on fucose. In the present study, it is shown that in wild-type cells the full synthesis of lactaldehyde dehydrogenase requires the presence of both molecular oxygen and a small molecule effector, and the full synthesis of lactaldehyde reductase requires anaerobiosis and the presence of a small molecule effector. The failure of mutant cells to grow on fucose reflects the impairment of a regulatory element in the fucose system that prevents the induction of the permease, the isomerase, and the kinase. The aldolase, on the other hand, is constitutively synthesized. Three independent fucose-utilizing revertants of the mutant all produce the permease, the isomerase, the kinase, as well as the aldolase, constitutively. These strains grow less well than the parental mutant on propanediol."} {"id": "PMID:181365", "title": "Regulation of lactate dehydrogenase activity in Rothia dentocariosa by fructose 1,6-diphosphate and adenosine 5'-triphosphate.", "content": "The L-(+)-lactate dehydrogenase from Rothia dentocariosa strain 17931 is activated by fructose 1,6-diphosphate and inhibited by adenosine 5'-triphosphate. The enzyme has a molecular weight of 120,000. In these respects, it resembles the lactate dehydrogenase of Actinomyces viscosus.", "contents": "Regulation of lactate dehydrogenase activity in Rothia dentocariosa by fructose 1,6-diphosphate and adenosine 5'-triphosphate. The L-(+)-lactate dehydrogenase from Rothia dentocariosa strain 17931 is activated by fructose 1,6-diphosphate and inhibited by adenosine 5'-triphosphate. The enzyme has a molecular weight of 120,000. In these respects, it resembles the lactate dehydrogenase of Actinomyces viscosus."} {"id": "PMID:181366", "title": "Effects of phthalate esters on the respiration of rat liver mitochondria.", "content": "The effects of phthalate esters on the oxidation of succinate, glutamate, beta-hydroxybutyrate and NADH by rat liver mitochondria were examined and it was found that di-n-butyl phthalate (DBP) strongly inhibited the succinate oxidation by intact and sonicated rat mitochondria, but did not inhibit the State 4 respiration with NAD-linked substrates such as glutamate and beta-hydroxybutyrate. However, oxygen uptake accelerated by the presence of ADP and substrate (State 3) was inhibited and the rate of oxygen uptake decreased to that without ADP (State 4). It was concluded that phthalate esters were electron and energy transport inhibitors but not uncouplers. Phthalate esters also inhibited NADH oxidation by sonicated mitochondria. The degree of inhibition depended on the carbon number of alkyl groups of phthalate esters, and DBP was the most potent inhibitor of respiration. The activity of purified beef liver glutamate dehydrogenase [EC 1.4.1.3] was slightly inhibited by phthalate esters.", "contents": "Effects of phthalate esters on the respiration of rat liver mitochondria. The effects of phthalate esters on the oxidation of succinate, glutamate, beta-hydroxybutyrate and NADH by rat liver mitochondria were examined and it was found that di-n-butyl phthalate (DBP) strongly inhibited the succinate oxidation by intact and sonicated rat mitochondria, but did not inhibit the State 4 respiration with NAD-linked substrates such as glutamate and beta-hydroxybutyrate. However, oxygen uptake accelerated by the presence of ADP and substrate (State 3) was inhibited and the rate of oxygen uptake decreased to that without ADP (State 4). It was concluded that phthalate esters were electron and energy transport inhibitors but not uncouplers. Phthalate esters also inhibited NADH oxidation by sonicated mitochondria. The degree of inhibition depended on the carbon number of alkyl groups of phthalate esters, and DBP was the most potent inhibitor of respiration. The activity of purified beef liver glutamate dehydrogenase [EC 1.4.1.3] was slightly inhibited by phthalate esters."} {"id": "PMID:181367", "title": "Proteoglycan complexes from bovine heart valve. Fractionation by density-gradient centrifugation and gel filtration under dissociative conditions.", "content": "Proteoglycan complexes from collagenase [EC 3.4.24.3]-indigestible materials of bovine heart valves were extracted with 4 M guanidinium chloride, purified by ion-exchange column chromatography in a urea-containing solution, then fractionated by density-gradient centrifugation under dissociative conditions. Electrophoretic characteristics and enzymic susceptibility of the density-gradient fractions revealed that the glycosaminoglycans constituting the proteoglycan complexes in this indigestible materials were mainly dermatan sulfate in the top three fractions, and dermatan sulfate and chondroitin sulfates in the bottom fraction; a minor constituent which was common to all the fractions was hyaluronic acid. A gel-like substance (Fr. Ig) at the top of the gradient, amounting to about 25% of the loaded dry sample, contained only a trace of hydroxyproline (less than 1%) and was composed of proteodermatan sulfate, glycoprotein, and a small amount of hyaluronic acid. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analyses of Fr. Ig with 2-mercaptoethanol showed that the major part of the proteins in this gel-like substance was cross-linked by disulfide bridges. Chromatography of Fr. Ig on Sepharose 4B in buffered 4 M guanidinium chloride containing 2-mercaptoethanol, together with the electrophoretic patterns of the resulting fractions, suggested that proteodermatan sulfate was not associated with hyaluronic acid through covalent bonds. The amino acid composition of Fr. Ig was very similar to that reported in the literature for \"dermatan sulfate-protein complex\", and \"structural glycoprotein\" or \"acidic structural protein\".", "contents": "Proteoglycan complexes from bovine heart valve. Fractionation by density-gradient centrifugation and gel filtration under dissociative conditions. Proteoglycan complexes from collagenase [EC 3.4.24.3]-indigestible materials of bovine heart valves were extracted with 4 M guanidinium chloride, purified by ion-exchange column chromatography in a urea-containing solution, then fractionated by density-gradient centrifugation under dissociative conditions. Electrophoretic characteristics and enzymic susceptibility of the density-gradient fractions revealed that the glycosaminoglycans constituting the proteoglycan complexes in this indigestible materials were mainly dermatan sulfate in the top three fractions, and dermatan sulfate and chondroitin sulfates in the bottom fraction; a minor constituent which was common to all the fractions was hyaluronic acid. A gel-like substance (Fr. Ig) at the top of the gradient, amounting to about 25% of the loaded dry sample, contained only a trace of hydroxyproline (less than 1%) and was composed of proteodermatan sulfate, glycoprotein, and a small amount of hyaluronic acid. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analyses of Fr. Ig with 2-mercaptoethanol showed that the major part of the proteins in this gel-like substance was cross-linked by disulfide bridges. Chromatography of Fr. Ig on Sepharose 4B in buffered 4 M guanidinium chloride containing 2-mercaptoethanol, together with the electrophoretic patterns of the resulting fractions, suggested that proteodermatan sulfate was not associated with hyaluronic acid through covalent bonds. The amino acid composition of Fr. Ig was very similar to that reported in the literature for \"dermatan sulfate-protein complex\", and \"structural glycoprotein\" or \"acidic structural protein\"."} {"id": "PMID:181368", "title": "Polarographic studies in presence of Triton X-100 on oxidation-reduction components bound with chromatophores from Rhodospirillum rubrum.", "content": "Polarographic studies on oxidation-reduction components bound with chromatophores from Rhodospirillum rubrum were carried out at 24 degrees. 1. Using a carbon-paste electrode as the working electrode, polarographic waves characteristic of oxidation-reduction components were observed in the presence, but not in the absence of Triton X-100; these waves were therefore measured in the presence of the detergent. 2. At least two kinds of oxidation-reduction components were detectable, having different half-wave potentials (E1/2); at pH 7, one had an E1/2 value of +275 mV (POC+275) and the other had a value of +60 mV (POC+60). 3. POC+275 was reduced by succinate and by NADH. Both reductions were almost completely inhibited by antimycin A, which hardly affected the reductions of ubiquinone-10 by succinate and by NADH. Most POC+275 molecules were not reduced by the substrates when quinones were extracted from the chromatophores, and the reductions were mostly restored when ubiquinone-10 was re-added. This indicates that POC+275 is functional between ubiquinone-10 and cytochrome c2 in the electron transport system. 4. POC+60 was reduced by succinate, but hardly at all by NADH. The reduction of POC+60 was not influenced either by the addition of antimycin A or by the extraction of quinones. This suggests that POC+60 is functional in the process from succinate dehydrogenase [EC 1.3.99.1] to ubiquinone-10 in the electron transport system. 5. Of the POC+275 reducible by dithionite, approximately 70% could be reduced in the absence of Triton X-100, provided that the potential of the working electrode immersed in chromatophore suspensions was set at potentials of 0 mV or lower and that the electrochemical reaction was carried out at pH 7.5. When the potential of the electrode was set at +50 mV (the same as the E1/2 value of ubiquinone-10 bound with chromatophores), and the suspension was allowed to stand for various lengths in the presence of the detergent, it was found that approximately half of the electrochemically reducible POC+275 was rapidly reduced, followed by a slow reduction. The discrepancy in the oxidation-reduction equilibrium on the basis of the E1/2 values of ubiquinone-10 and POC+275 is discussed.", "contents": "Polarographic studies in presence of Triton X-100 on oxidation-reduction components bound with chromatophores from Rhodospirillum rubrum. Polarographic studies on oxidation-reduction components bound with chromatophores from Rhodospirillum rubrum were carried out at 24 degrees. 1. Using a carbon-paste electrode as the working electrode, polarographic waves characteristic of oxidation-reduction components were observed in the presence, but not in the absence of Triton X-100; these waves were therefore measured in the presence of the detergent. 2. At least two kinds of oxidation-reduction components were detectable, having different half-wave potentials (E1/2); at pH 7, one had an E1/2 value of +275 mV (POC+275) and the other had a value of +60 mV (POC+60). 3. POC+275 was reduced by succinate and by NADH. Both reductions were almost completely inhibited by antimycin A, which hardly affected the reductions of ubiquinone-10 by succinate and by NADH. Most POC+275 molecules were not reduced by the substrates when quinones were extracted from the chromatophores, and the reductions were mostly restored when ubiquinone-10 was re-added. This indicates that POC+275 is functional between ubiquinone-10 and cytochrome c2 in the electron transport system. 4. POC+60 was reduced by succinate, but hardly at all by NADH. The reduction of POC+60 was not influenced either by the addition of antimycin A or by the extraction of quinones. This suggests that POC+60 is functional in the process from succinate dehydrogenase [EC 1.3.99.1] to ubiquinone-10 in the electron transport system. 5. Of the POC+275 reducible by dithionite, approximately 70% could be reduced in the absence of Triton X-100, provided that the potential of the working electrode immersed in chromatophore suspensions was set at potentials of 0 mV or lower and that the electrochemical reaction was carried out at pH 7.5. When the potential of the electrode was set at +50 mV (the same as the E1/2 value of ubiquinone-10 bound with chromatophores), and the suspension was allowed to stand for various lengths in the presence of the detergent, it was found that approximately half of the electrochemically reducible POC+275 was rapidly reduced, followed by a slow reduction. The discrepancy in the oxidation-reduction equilibrium on the basis of the E1/2 values of ubiquinone-10 and POC+275 is discussed."} {"id": "PMID:181369", "title": "Competitive inhibition of hexokinase isoenzymes by mercurials.", "content": "A difference in the mode of inhibition of hexokinase [EC 2.7.1.1] isoenzymes by p-chloromercuribenzenesulfonate was confirmed with respect to glucose between two Type I isoenzyme preparations purified from the kidney and spleen of rat. Essentially the same difference was observed when galactose was used as the substrate in place of glucose, as the kidney Type I isoenzyme was inhibited in a competitive manner while the spleen counterpart was inhibited in a non-competitive manner by sulfhydryl inhibitor. Both the Type I isoenzymes, however, were competitively inhibited by other mercurial sulfhydryl inhibitors, methyl and butyl mercuric chlorides. On the other hand, the Type II hexokinase isoenzymes purified from the muscle, heart, and spleen were all inhibited competitively by p-chloromercuribenzenesulfonate with respect to glucose. The mechanism of competitive inhibition of the hexokinase isoenzymes by sulfhydryl inhibitors was discussed in view of the difference in the mode of action of the mercurials with different isoenzymes.", "contents": "Competitive inhibition of hexokinase isoenzymes by mercurials. A difference in the mode of inhibition of hexokinase [EC 2.7.1.1] isoenzymes by p-chloromercuribenzenesulfonate was confirmed with respect to glucose between two Type I isoenzyme preparations purified from the kidney and spleen of rat. Essentially the same difference was observed when galactose was used as the substrate in place of glucose, as the kidney Type I isoenzyme was inhibited in a competitive manner while the spleen counterpart was inhibited in a non-competitive manner by sulfhydryl inhibitor. Both the Type I isoenzymes, however, were competitively inhibited by other mercurial sulfhydryl inhibitors, methyl and butyl mercuric chlorides. On the other hand, the Type II hexokinase isoenzymes purified from the muscle, heart, and spleen were all inhibited competitively by p-chloromercuribenzenesulfonate with respect to glucose. The mechanism of competitive inhibition of the hexokinase isoenzymes by sulfhydryl inhibitors was discussed in view of the difference in the mode of action of the mercurials with different isoenzymes."} {"id": "PMID:181370", "title": "Chemical modification of the Ca2+-dependent ATPase of sarcoplasmic reticulum from skeletal muscle. I. Binding of N-ethylmaleimide to sarcoplasmic reticulum: evidence for sulfhydryl groups in the active site of ATPase and for conformational changes induced by adenosine tri- and diphosphate.", "content": "The time course of binding of N-ethylmaleimide (NEM) to the SR was measured at pH 7.5 in the presence or absence of ATP or ADP. The following results were obtained. 1. Both in the presence and absence of nucleotide, the ATPase [EC 3.6.1.3] activity decreased linearly with increase in the amount of NEM bound to the fragmented sarcoplasmic reticulum (SR), and was inhibited almost completely by the binding of 2 moles of NEM per 10(5) g of the SR protein. 2. The amount of NEM incorporated into the ATPase (M.W.=105,000) was measured by SDS disc-gel electrophoresis. It was shown that the ATPase activity was inhibited almost completely by the binding of 2 moles of NEM per mole of ATPase. 3. The rate of binding of NEM to SR decreased by 30-40% in the presence of either ATP or ADP. The concentrations of both ATP and ADP for half-saturation were 0.1-0.2mM. 4. The effect of nucleotide on the rate of binding of NEM was not changed by the presence of Ca2+ and Mg2+ ions. Similar effects were also observed even when the SR membranes were solubilized with Triton X-100. It is suggested from these results that one or two SH groups are located in the active site of the SR ATPase, and that conformational changes are induced by the addition of ATP and ADP.", "contents": "Chemical modification of the Ca2+-dependent ATPase of sarcoplasmic reticulum from skeletal muscle. I. Binding of N-ethylmaleimide to sarcoplasmic reticulum: evidence for sulfhydryl groups in the active site of ATPase and for conformational changes induced by adenosine tri- and diphosphate. The time course of binding of N-ethylmaleimide (NEM) to the SR was measured at pH 7.5 in the presence or absence of ATP or ADP. The following results were obtained. 1. Both in the presence and absence of nucleotide, the ATPase [EC 3.6.1.3] activity decreased linearly with increase in the amount of NEM bound to the fragmented sarcoplasmic reticulum (SR), and was inhibited almost completely by the binding of 2 moles of NEM per 10(5) g of the SR protein. 2. The amount of NEM incorporated into the ATPase (M.W.=105,000) was measured by SDS disc-gel electrophoresis. It was shown that the ATPase activity was inhibited almost completely by the binding of 2 moles of NEM per mole of ATPase. 3. The rate of binding of NEM to SR decreased by 30-40% in the presence of either ATP or ADP. The concentrations of both ATP and ADP for half-saturation were 0.1-0.2mM. 4. The effect of nucleotide on the rate of binding of NEM was not changed by the presence of Ca2+ and Mg2+ ions. Similar effects were also observed even when the SR membranes were solubilized with Triton X-100. It is suggested from these results that one or two SH groups are located in the active site of the SR ATPase, and that conformational changes are induced by the addition of ATP and ADP."} {"id": "PMID:181371", "title": "The subunits of Chlorobium flavocytochrome c.", "content": "The subunits of cytochrome c-553 (Chlorobium thiosulfatophilum) were studied. The cytochrome is split into a cytochrome moiety and a flavoprotein moiety by treatment with 2% trichloroacetic acid. The molecular weights of the cytochrome and flavoprotein moieties are 11,000 and 47,000, respectively. The cytochrome moiety seems to have only one cysteine residue in the molecule, although its heme appears to be quite similar to the usual heme c. The flavoprotein moiety shows absorption peaks at 350 and 452nm and is insoluble at neutral pH. When the two moieties are mixed at alkaline pH, and the pH of the mixture is then brought to neutral, the flavoprotein moiety remains soluble. However, the preparation thus obtained is different from the original cytochrome c-553.", "contents": "The subunits of Chlorobium flavocytochrome c. The subunits of cytochrome c-553 (Chlorobium thiosulfatophilum) were studied. The cytochrome is split into a cytochrome moiety and a flavoprotein moiety by treatment with 2% trichloroacetic acid. The molecular weights of the cytochrome and flavoprotein moieties are 11,000 and 47,000, respectively. The cytochrome moiety seems to have only one cysteine residue in the molecule, although its heme appears to be quite similar to the usual heme c. The flavoprotein moiety shows absorption peaks at 350 and 452nm and is insoluble at neutral pH. When the two moieties are mixed at alkaline pH, and the pH of the mixture is then brought to neutral, the flavoprotein moiety remains soluble. However, the preparation thus obtained is different from the original cytochrome c-553."} {"id": "PMID:181372", "title": "Properties of purified hydrogenase from the particulate fraction of Desulfovibrio vulgaris, Miyazaki.", "content": "The properties of purified hydrogenase [EC 1.12.2.1] solubilized from particulate fraction of sonicated Desulfovibrio vulgaris cells are described. The enzyme was a brownish iron-sulfur protein of molecular weight 89,000, composed of two different subunits (mol. wt.: 28,000 and 59,000), and it contained 7-9 iron atoms and 7-8 labile sulfide ions. Molybdenum was not detected in the preparation. The absorption spectrum of the enzyme was characteristic of iron-sulfur proteins. The millimolar absorbance coefficients of the enzyme were about 164 at 280nm, and 47 at 400nm. The absorption spectrum of the enzyme in the visible region changed upon incubating the enzyme under H2 in the presence of cytochrome c3, but not in its absence. This spectral change was due to the reduction of the enzyme. The absorbance ratio at 400nm of the reduced and the oxidized forms of the enzyme was 0.66. The activity of the enzyme was hardly affected by metal-complexing agents such as cyanide, azide, 1,10-phenanthroline, etc., except for CO, which was a strong inhibitor of the enzyme. The activity was inhibited by SH-reagents such as p-chloromercuribenzenesulfonate. The enzyme was significantly resistant to urea, but susceptible to sodium dodecyl sulfate. These properties were very similar to those of clostridial hydrogenase [EC 1.12.7.1], in spite of differences in the acceptor specificity and subunit structure.", "contents": "Properties of purified hydrogenase from the particulate fraction of Desulfovibrio vulgaris, Miyazaki. The properties of purified hydrogenase [EC 1.12.2.1] solubilized from particulate fraction of sonicated Desulfovibrio vulgaris cells are described. The enzyme was a brownish iron-sulfur protein of molecular weight 89,000, composed of two different subunits (mol. wt.: 28,000 and 59,000), and it contained 7-9 iron atoms and 7-8 labile sulfide ions. Molybdenum was not detected in the preparation. The absorption spectrum of the enzyme was characteristic of iron-sulfur proteins. The millimolar absorbance coefficients of the enzyme were about 164 at 280nm, and 47 at 400nm. The absorption spectrum of the enzyme in the visible region changed upon incubating the enzyme under H2 in the presence of cytochrome c3, but not in its absence. This spectral change was due to the reduction of the enzyme. The absorbance ratio at 400nm of the reduced and the oxidized forms of the enzyme was 0.66. The activity of the enzyme was hardly affected by metal-complexing agents such as cyanide, azide, 1,10-phenanthroline, etc., except for CO, which was a strong inhibitor of the enzyme. The activity was inhibited by SH-reagents such as p-chloromercuribenzenesulfonate. The enzyme was significantly resistant to urea, but susceptible to sodium dodecyl sulfate. These properties were very similar to those of clostridial hydrogenase [EC 1.12.7.1], in spite of differences in the acceptor specificity and subunit structure."} {"id": "PMID:181373", "title": "Stepwise degradation of serum low denisty lipoprotein by sodium dodecyl sulfate.", "content": "The structure of human serum low density lipoprotein (LDL) was investigated by perturbing the LDL structure with sodium dodecyl sulfate (SDS). The change in LDL structure induced by the addition of SDS was monitored by sedimentation velocity measurements, ultraviolet difference spectroscopy, fluorescence spectroscopy and proteolytic digestion of apo-LDL with subtilisin BPN' [EC 3.4.21.14]. As the concentration of SDS was increased from 0.1 mg/ml to 3 mg/ml with LDL concentrations between 2.0 mg/ml and 4.4 mg/ml, the sedimentation coefficient of LDL changed in three distinct steps. It was found by chemical analyses that not more than 30% of the total lipid was lost from LDL in the second step, whereas the final step in the change of sedimentation coefficient corresponded to the complete removal of apo-LDL from the constituent lipids of LDL. The ultraviolet difference spectrum between the native and SDS-treated LDL and the quenching of LDL fluorescence underwent about 80% of the total change while the SDS concentration was only sufficient to cause the second of the three step changes in sedimentation coefficient. SDS-polyacrylamide gel electrophoresis of apo-LDL treated with subtilisin BPN' also showed that more than 70% of apo-LDL became susceptible to proteolysis under the same conditions. These results were interpreted as indicating that the solubilization of 20 to 30% of the lipids on the surface of LDL exposed nearly 80% or more of apo-LDL to the solvent. A small portion of apo-LDL was, however, still firmly anchored to the remaining lipid micelle as long as the concentration of SDS was less than that required to cause the final step of the change in sedimentation coefficient.", "contents": "Stepwise degradation of serum low denisty lipoprotein by sodium dodecyl sulfate. The structure of human serum low density lipoprotein (LDL) was investigated by perturbing the LDL structure with sodium dodecyl sulfate (SDS). The change in LDL structure induced by the addition of SDS was monitored by sedimentation velocity measurements, ultraviolet difference spectroscopy, fluorescence spectroscopy and proteolytic digestion of apo-LDL with subtilisin BPN' [EC 3.4.21.14]. As the concentration of SDS was increased from 0.1 mg/ml to 3 mg/ml with LDL concentrations between 2.0 mg/ml and 4.4 mg/ml, the sedimentation coefficient of LDL changed in three distinct steps. It was found by chemical analyses that not more than 30% of the total lipid was lost from LDL in the second step, whereas the final step in the change of sedimentation coefficient corresponded to the complete removal of apo-LDL from the constituent lipids of LDL. The ultraviolet difference spectrum between the native and SDS-treated LDL and the quenching of LDL fluorescence underwent about 80% of the total change while the SDS concentration was only sufficient to cause the second of the three step changes in sedimentation coefficient. SDS-polyacrylamide gel electrophoresis of apo-LDL treated with subtilisin BPN' also showed that more than 70% of apo-LDL became susceptible to proteolysis under the same conditions. These results were interpreted as indicating that the solubilization of 20 to 30% of the lipids on the surface of LDL exposed nearly 80% or more of apo-LDL to the solvent. A small portion of apo-LDL was, however, still firmly anchored to the remaining lipid micelle as long as the concentration of SDS was less than that required to cause the final step of the change in sedimentation coefficient."} {"id": "PMID:181374", "title": "Comparison of calcium-binding proteins. Bovine heart and brain protein activators of cyclic nucleotide phosphodiesterase and rabbit skeletal muscle troponin C.", "content": "In previous studies we have shown that the activation of bovine heart cyclic nucleotide phosphodiesterase by purified protein activator is completely dependent on the presence of Ca2+ and that the protein activator Ca2+ complex is probably the true activator for the enzyme (Teo, T.S. and Wang, J.H. (1973) J. Biol. Chem. 248, 5930-5955). More recent studies have led us to believe that the mechanism of the Ca2+ activation of phosphodiesterase resembles that of the Ca2+ activation of muscle contraction and that the protein activator may play a role similar to troponin. In the present study we show that the protein activator resembles rabbit muscle troponin C in amino acid composition, molecular weight, isoelectric point, and ultraviolet absorption spectrum. Preliminary structural studies also indicate that these two proteins may have evolved from a common ancestral protein through gene duplication. This argument is strengthened by the finding that the tryptic peptide map of the bovine heart protein activator is indistinguishable from that of the bovine brain phosphodiesterase activator protein for which preliminary sequence information also suggests homology to troponin C (Watterson, D.M., Harrelson, W.G., Jr., Keller, P.M., Sharief, F., and Vanaman, T.C. (1976) J. Biol. Chem. 251, 4501-4513).", "contents": "Comparison of calcium-binding proteins. Bovine heart and brain protein activators of cyclic nucleotide phosphodiesterase and rabbit skeletal muscle troponin C. In previous studies we have shown that the activation of bovine heart cyclic nucleotide phosphodiesterase by purified protein activator is completely dependent on the presence of Ca2+ and that the protein activator Ca2+ complex is probably the true activator for the enzyme (Teo, T.S. and Wang, J.H. (1973) J. Biol. Chem. 248, 5930-5955). More recent studies have led us to believe that the mechanism of the Ca2+ activation of phosphodiesterase resembles that of the Ca2+ activation of muscle contraction and that the protein activator may play a role similar to troponin. In the present study we show that the protein activator resembles rabbit muscle troponin C in amino acid composition, molecular weight, isoelectric point, and ultraviolet absorption spectrum. Preliminary structural studies also indicate that these two proteins may have evolved from a common ancestral protein through gene duplication. This argument is strengthened by the finding that the tryptic peptide map of the bovine heart protein activator is indistinguishable from that of the bovine brain phosphodiesterase activator protein for which preliminary sequence information also suggests homology to troponin C (Watterson, D.M., Harrelson, W.G., Jr., Keller, P.M., Sharief, F., and Vanaman, T.C. (1976) J. Biol. Chem. 251, 4501-4513)."} {"id": "PMID:181375", "title": "Structural similarities between the Ca2+-dependent regulatory proteins of 3':5'-cyclic nucleotide phosphodiesterase and actomyosin ATPase.", "content": "Results of studies of the Ca2+-dependent protein modulator of 3':5'-cyclic nucleotide phosphodiesterase isolated from bovine brain are presented which show its structural similarity to the Ca2+-binding subunit of muscle troponin. Both proteins have blocked NH2 termini, similar and characteristic ultraviolet absorption spectra, similar Ca2+-binding properties, very similar amino acid compositions, and co-migrate on sodium dodecyl sulfate-polyacrylamide gels. The primary structures of selected tryptic peptides isolated from bovine brain modulator protein are similar or identical with regions of the primary sequences of rabbit skeletal muscle and bovine cardiac muscle troponin C. Bovine brain modulator protein contains and unidentified ninhydrin-positive basic compound not found in muscle troponin C. An improved procedure is presented which yields 40 to 70 mg of modulator protein per kg of bovine brain.", "contents": "Structural similarities between the Ca2+-dependent regulatory proteins of 3':5'-cyclic nucleotide phosphodiesterase and actomyosin ATPase. Results of studies of the Ca2+-dependent protein modulator of 3':5'-cyclic nucleotide phosphodiesterase isolated from bovine brain are presented which show its structural similarity to the Ca2+-binding subunit of muscle troponin. Both proteins have blocked NH2 termini, similar and characteristic ultraviolet absorption spectra, similar Ca2+-binding properties, very similar amino acid compositions, and co-migrate on sodium dodecyl sulfate-polyacrylamide gels. The primary structures of selected tryptic peptides isolated from bovine brain modulator protein are similar or identical with regions of the primary sequences of rabbit skeletal muscle and bovine cardiac muscle troponin C. Bovine brain modulator protein contains and unidentified ninhydrin-positive basic compound not found in muscle troponin C. An improved procedure is presented which yields 40 to 70 mg of modulator protein per kg of bovine brain."} {"id": "PMID:181376", "title": "Interaction of cyclic adenosine 3':5'-monophosphate with protein kinase. Equilibrium binding models.", "content": "A number of potential models for the interaction of cyclic AMP with protein kinase (RC or R2C2) have been examined. These include: Model 1, the simultaneous binding of cyclic AMP and release of C (catalytic subunit) from an independent RC protomer; Model 2, dissociation of an independent RC protomer prior to cyclic AMP binding to R (regulatory subunit); Model 3, cyclic AMP binding to RC prior to the dissociation of C; Model 4, random binding of cyclic AMP and dissociation of C with an interaction factor alpha less than 1; Model 5, release of 2C concomitant with the binding of one cyclic AMP to R2C2 followed by binding of the second cyclic AMP to the vacant R subunit; and Model 6, the simultaneous binding of cyclic AMP and release of C from one RC protomer resulting in a greater \"affinity\" of the other RC protomer for cyclic AMP, i.e., a cooperative version of Model 1. All the above models yield [cyclic AMP]0.5 values that increase with increasing protein concentration and Hill plots with average slopes equal to or less than 1.0 in the usual experimental range (10 to 90% of saturation). The Hill plots can be nonlinear, but for each model the exact shape of the plot changes in a characteristic (diagnostic) manner with changing protein concentration. Skeletal muscle protein kinase yields relatively linear Hill plots with napp values greater than 1.0. Consequently, Models 1 to 6 are not likely candidates. However, Model 2 is an excellent alternative model for proteins that display \"negative cooperativity\" with respect to the binding of a ligand. The properties of several \"linear\", \"tetrahedral\", and \"all-or-nothing\" cooperative models have also been examined. These include Models 7, A, B, and C and 8, A, B, and C which are cooperative versions of Models 2 and 3, respectively, and Model 9, a cooperative version of random Model 4. Model 9 is the most general model from which all others can be derived. Models 9 and 7, A, B, and C in which the prior dissociation of C greatly enhances or is an absolute requirement for cyclic AMP binding to R, are likely candidates for skeletal muscle protein kinase. All four of these models are capable of yielding Hill plots with average slopes greater than 1, and napp values that decrease with increasing protein concentration (in agreement with published data). In addition, in all four models the tight binding of MgATP to R2C2 yields decreased napp values and increased [cyclic AMP]0.5 values (also consistent with published data).", "contents": "Interaction of cyclic adenosine 3':5'-monophosphate with protein kinase. Equilibrium binding models. A number of potential models for the interaction of cyclic AMP with protein kinase (RC or R2C2) have been examined. These include: Model 1, the simultaneous binding of cyclic AMP and release of C (catalytic subunit) from an independent RC protomer; Model 2, dissociation of an independent RC protomer prior to cyclic AMP binding to R (regulatory subunit); Model 3, cyclic AMP binding to RC prior to the dissociation of C; Model 4, random binding of cyclic AMP and dissociation of C with an interaction factor alpha less than 1; Model 5, release of 2C concomitant with the binding of one cyclic AMP to R2C2 followed by binding of the second cyclic AMP to the vacant R subunit; and Model 6, the simultaneous binding of cyclic AMP and release of C from one RC protomer resulting in a greater \"affinity\" of the other RC protomer for cyclic AMP, i.e., a cooperative version of Model 1. All the above models yield [cyclic AMP]0.5 values that increase with increasing protein concentration and Hill plots with average slopes equal to or less than 1.0 in the usual experimental range (10 to 90% of saturation). The Hill plots can be nonlinear, but for each model the exact shape of the plot changes in a characteristic (diagnostic) manner with changing protein concentration. Skeletal muscle protein kinase yields relatively linear Hill plots with napp values greater than 1.0. Consequently, Models 1 to 6 are not likely candidates. However, Model 2 is an excellent alternative model for proteins that display \"negative cooperativity\" with respect to the binding of a ligand. The properties of several \"linear\", \"tetrahedral\", and \"all-or-nothing\" cooperative models have also been examined. These include Models 7, A, B, and C and 8, A, B, and C which are cooperative versions of Models 2 and 3, respectively, and Model 9, a cooperative version of random Model 4. Model 9 is the most general model from which all others can be derived. Models 9 and 7, A, B, and C in which the prior dissociation of C greatly enhances or is an absolute requirement for cyclic AMP binding to R, are likely candidates for skeletal muscle protein kinase. All four of these models are capable of yielding Hill plots with average slopes greater than 1, and napp values that decrease with increasing protein concentration (in agreement with published data). In addition, in all four models the tight binding of MgATP to R2C2 yields decreased napp values and increased [cyclic AMP]0.5 values (also consistent with published data)."} {"id": "PMID:181377", "title": "Sphingolipid base metabolism. Partial purification and properties of sphinganine kinase of brain.", "content": "The presence of sphinganine kinase in bovine brain has been demonstrated. The product of the action of the brain enzyme on sphinganine has been characterized as sphingamine 1-phosphate by a combination of chemical, enzymatic, and chromatographic techniques. The bovine brain enzyme has been partially purified and appears to exist in multiple forms. The molecular weight of the most highly purified preparation of the enzyme was estimated to be 190,000 by gel filtration. The purified form of the enzyme showed highest activity with ATP but was also active with other purine nucleoside triphosphates. UTP and CTP did not serve as substrates for the enzyme.", "contents": "Sphingolipid base metabolism. Partial purification and properties of sphinganine kinase of brain. The presence of sphinganine kinase in bovine brain has been demonstrated. The product of the action of the brain enzyme on sphinganine has been characterized as sphingamine 1-phosphate by a combination of chemical, enzymatic, and chromatographic techniques. The bovine brain enzyme has been partially purified and appears to exist in multiple forms. The molecular weight of the most highly purified preparation of the enzyme was estimated to be 190,000 by gel filtration. The purified form of the enzyme showed highest activity with ATP but was also active with other purine nucleoside triphosphates. UTP and CTP did not serve as substrates for the enzyme."} {"id": "PMID:181378", "title": "Detection of an essential sulfhydryl group in phosphoglycerate mutase with an affinity-labeling reagent.", "content": "N-Bromoacetylethanolamine phosphate rapidly and irreversibly inactivates rabbit muscle phosphoglycerate mutase. At high molar ratios of reagent to enzyme, loss of activity (both mutase and phosphatase) approximates pseudo-first order kinetics. A rate-saturation effect is observed with half-maximal rate of inactivation occurring at 0.32 mM reagent, a value close to the Km for 3-phosphoglyceric acid. This datum and the dissociation constant of the 2,3-bisphosphoglycerate-enzyme complex, as determined from inactivation kinetics in the presence of the bisphosphate, suggest that the reagent reacts at the substrate binding site. Inactivation results from the covalent incorporation of about 0.8 mol of reagent/mol of catalytic subunit as determined with 14C-labeled reagent. Incorporation is negligible in the presence of substrate and is reduced 8-fold in the presence of 6 M urea. From amino acid analyses on acid hydrolysates of the inactivated enzyme, we have identified a sulfhydryl group as the site of alkylation. A peptide containing the essential sulfhydryl group has been isolated from a tryptic digest of the enzyme inactivated with labeled reagent; its amino acid composition is Trp1, Lys1,-Cys(Cm)1, Asp1, Ser1, Glu2, Gly1, Ala1, Leu1, Phe2.", "contents": "Detection of an essential sulfhydryl group in phosphoglycerate mutase with an affinity-labeling reagent. N-Bromoacetylethanolamine phosphate rapidly and irreversibly inactivates rabbit muscle phosphoglycerate mutase. At high molar ratios of reagent to enzyme, loss of activity (both mutase and phosphatase) approximates pseudo-first order kinetics. A rate-saturation effect is observed with half-maximal rate of inactivation occurring at 0.32 mM reagent, a value close to the Km for 3-phosphoglyceric acid. This datum and the dissociation constant of the 2,3-bisphosphoglycerate-enzyme complex, as determined from inactivation kinetics in the presence of the bisphosphate, suggest that the reagent reacts at the substrate binding site. Inactivation results from the covalent incorporation of about 0.8 mol of reagent/mol of catalytic subunit as determined with 14C-labeled reagent. Incorporation is negligible in the presence of substrate and is reduced 8-fold in the presence of 6 M urea. From amino acid analyses on acid hydrolysates of the inactivated enzyme, we have identified a sulfhydryl group as the site of alkylation. A peptide containing the essential sulfhydryl group has been isolated from a tryptic digest of the enzyme inactivated with labeled reagent; its amino acid composition is Trp1, Lys1,-Cys(Cm)1, Asp1, Ser1, Glu2, Gly1, Ala1, Leu1, Phe2."} {"id": "PMID:181379", "title": "Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate.", "content": "Secretin and vasoactive intestinal peptide (VIP), but not glucagon, stimulate accumulation of cyclic AMP in dispersed guinea pig pancreatic acinar cells. Secretin stimulated cellular accumulation of cyclic AMP by interacting with a single class of high affinity receptors. On the other hand, the dose-response curve for VIP-stimulated cellular cyclic AMP was biphasic and reflected interaction of this peptide with two classes of receptors. Results obtained with synthetic fragments of VIP and secretin indicate that the receptor having a high affinity for VIP has a low affinity for secretin, interacts with, but does not distinguish among, secretin, secretin 5-27 and [6-tyrosine] secretin or among secretin 14-27, VIP 14-28, VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, but not when occupied by secretin, [6-tyrosine] secretin, or secretin 1-14. The receptor having a low affinity for VIP has a high affinity for secretin, interacts with and distinguishes among secretin, secretin 5-27, and [6-tyrosine] secretin, interacts with secretin 14-27 but not with VIP 14-28 or VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, secretin, [6-tyrosine] secretin, or secretin 1-14.", "contents": "Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate. Secretin and vasoactive intestinal peptide (VIP), but not glucagon, stimulate accumulation of cyclic AMP in dispersed guinea pig pancreatic acinar cells. Secretin stimulated cellular accumulation of cyclic AMP by interacting with a single class of high affinity receptors. On the other hand, the dose-response curve for VIP-stimulated cellular cyclic AMP was biphasic and reflected interaction of this peptide with two classes of receptors. Results obtained with synthetic fragments of VIP and secretin indicate that the receptor having a high affinity for VIP has a low affinity for secretin, interacts with, but does not distinguish among, secretin, secretin 5-27 and [6-tyrosine] secretin or among secretin 14-27, VIP 14-28, VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, but not when occupied by secretin, [6-tyrosine] secretin, or secretin 1-14. The receptor having a low affinity for VIP has a high affinity for secretin, interacts with and distinguishes among secretin, secretin 5-27, and [6-tyrosine] secretin, interacts with secretin 14-27 but not with VIP 14-28 or VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, secretin, [6-tyrosine] secretin, or secretin 1-14."} {"id": "PMID:181380", "title": "Action of cholecystokinin, cholinergic agents, and A-23187 on accumulation of guanosine 3':5'-monophosphate in dispersed guinea pig pancreatic acinar cells.", "content": "The COOH-terminal octapeptide of cholecystokinin (CCK-OP) and carbamylcholine each increased calcium outflux, cellular cyclic GMP and amylase secretion in dispersed guinea pig pancreatic acinar cells. Following addition of CCK-OP or carbamylcholine, cellular cyclic GMP increased as early as 15 s, became maximal after 1 to 2 min, and then decreased steadily during the subsequent incubation. For both CCK-OP and carbamylcholine there was close agreement between the dose-response curve for stimulation of calcium outflux and that for increase of cellular cyclic GMP. With CCK-OP an effect on both functions could be detected at 10(-10) M and maximal stimulation occurred at 3 X 10(-8) M. With carbamylcholine an effect on both functions could be detected at 10(-5) M and maximal stimulation occurred at 3 X 10(-3) M. Atropine inhibited stimulation of both cyclic GMP and calcium outflux by carbamylcholine but not by CCK-OP. Stimulation of calcium outflux or cellular cyclic GMP by CCK-OP or carbamylcholine did not require extracellular calcium since stimulation occurred in a calcium-free, ethylene glycol bis(beta, beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA)-containing solution. The divalent cation ionophore A-23187 increased bidirectional fluxes of calcium, cellular cyclic GMP and secretion of amylase from dispersed pancreatic acinar cells. Like CCK-OP and carbamylcholine, the ionophore stimulated calcium outflux and cellular cyclic GMP in a calcium-free, EGTA-containing solution. These results suggest that in pancreatic acinar cells the initial step in the sequence of events mediating the action of ionophore as well as that of CCK-OP and carbamylcholine is stimulation of calcium outflux, and that this stimulation then increases cellular cyclic GMP.", "contents": "Action of cholecystokinin, cholinergic agents, and A-23187 on accumulation of guanosine 3':5'-monophosphate in dispersed guinea pig pancreatic acinar cells. The COOH-terminal octapeptide of cholecystokinin (CCK-OP) and carbamylcholine each increased calcium outflux, cellular cyclic GMP and amylase secretion in dispersed guinea pig pancreatic acinar cells. Following addition of CCK-OP or carbamylcholine, cellular cyclic GMP increased as early as 15 s, became maximal after 1 to 2 min, and then decreased steadily during the subsequent incubation. For both CCK-OP and carbamylcholine there was close agreement between the dose-response curve for stimulation of calcium outflux and that for increase of cellular cyclic GMP. With CCK-OP an effect on both functions could be detected at 10(-10) M and maximal stimulation occurred at 3 X 10(-8) M. With carbamylcholine an effect on both functions could be detected at 10(-5) M and maximal stimulation occurred at 3 X 10(-3) M. Atropine inhibited stimulation of both cyclic GMP and calcium outflux by carbamylcholine but not by CCK-OP. Stimulation of calcium outflux or cellular cyclic GMP by CCK-OP or carbamylcholine did not require extracellular calcium since stimulation occurred in a calcium-free, ethylene glycol bis(beta, beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA)-containing solution. The divalent cation ionophore A-23187 increased bidirectional fluxes of calcium, cellular cyclic GMP and secretion of amylase from dispersed pancreatic acinar cells. Like CCK-OP and carbamylcholine, the ionophore stimulated calcium outflux and cellular cyclic GMP in a calcium-free, EGTA-containing solution. These results suggest that in pancreatic acinar cells the initial step in the sequence of events mediating the action of ionophore as well as that of CCK-OP and carbamylcholine is stimulation of calcium outflux, and that this stimulation then increases cellular cyclic GMP."} {"id": "PMID:181381", "title": "Properties of the interaction between bovine thyrotropin and bovine thyroid plasma membranes.", "content": "Studies have been conducted to characterize further the interaction between 125I-labeled bovine thyrotropin (TSH) and bovine thyroid plasma membranes. Sequential subcellular fractionation of thyroid homogenates yielded preparations of progressively greater specific binding activity, highest activity being found in fractions previously shown to contain predominately plasma membranes (Amir, S. M., Carraway, T.F., Kohn, L.D., and Winand, R.J. (1973) J. Biol. Chem. 248, 4092-4100). Although binding of 125I-TSH by plasma membranes was greatest at pH 6.0, studies were conducted at pH 7.45 as well as pH 6.0, and results obtained differed quantitatively, but not qualitatively. Binding was maximal at 0 degrees, 15 degrees, and 22 degrees and steady state values remained unchanged for at least 22 hours. At 37 degrees, binding was decreased by 40% at 1 hour; the loss was even greater (65%) at 50 degrees. A similar loss of binding was evident when membranes were preincubated without TSH at 37 degrees or higher and were then incubated with 125I-TSH at 0 degrees. Lineweaver-Burk analysis indicated that preincubation resulted in loss of receptor sites without change in affinity of residual receptors. Addition of Ca2+ (1 to 10 mM) to the preincubation medium prevented the effect of preincubation at 37 degrees by preserving the number of receptor sites without altering their affinity. Under similar conditions, Na+ and K+ were without protective effect. Membranes bound 45Ca2+ in a specific and saturable manner. Scatchard plots indicated a dissociatiion constant (Kd) of 9 X 10(-5) M and a capacity (n) of 54 nmol/mg of membrane protein. 45Ca2+ was also displaced from membranes by Mg2+ and Mn2+. Ca2+ had a biphasic effect on binding; low concentrations (1 to 10 muM) added to the incubation mixture stimulated binding, while higher concentrations (0.1 mM) caused inhibition. Mg2+ and Mn2+, at comparable concentrations, were also inhibitory, Na+ and K+ less so. In the case of Ca2+, both the stimulatory and inhibitory concentrations were lower than those required to achieve saturation of Ca2+-binding sites. Proteolytic enzymes (trypsin, alpha-chymotrypsin, and pronase) sharply reduced binding of 125I-TSH, owing to a decrease in receptor sites. Phospholipases A and C enhanced binding of TSH, while neuraminidase and beta-galactosidase were without measurable effect.", "contents": "Properties of the interaction between bovine thyrotropin and bovine thyroid plasma membranes. Studies have been conducted to characterize further the interaction between 125I-labeled bovine thyrotropin (TSH) and bovine thyroid plasma membranes. Sequential subcellular fractionation of thyroid homogenates yielded preparations of progressively greater specific binding activity, highest activity being found in fractions previously shown to contain predominately plasma membranes (Amir, S. M., Carraway, T.F., Kohn, L.D., and Winand, R.J. (1973) J. Biol. Chem. 248, 4092-4100). Although binding of 125I-TSH by plasma membranes was greatest at pH 6.0, studies were conducted at pH 7.45 as well as pH 6.0, and results obtained differed quantitatively, but not qualitatively. Binding was maximal at 0 degrees, 15 degrees, and 22 degrees and steady state values remained unchanged for at least 22 hours. At 37 degrees, binding was decreased by 40% at 1 hour; the loss was even greater (65%) at 50 degrees. A similar loss of binding was evident when membranes were preincubated without TSH at 37 degrees or higher and were then incubated with 125I-TSH at 0 degrees. Lineweaver-Burk analysis indicated that preincubation resulted in loss of receptor sites without change in affinity of residual receptors. Addition of Ca2+ (1 to 10 mM) to the preincubation medium prevented the effect of preincubation at 37 degrees by preserving the number of receptor sites without altering their affinity. Under similar conditions, Na+ and K+ were without protective effect. Membranes bound 45Ca2+ in a specific and saturable manner. Scatchard plots indicated a dissociatiion constant (Kd) of 9 X 10(-5) M and a capacity (n) of 54 nmol/mg of membrane protein. 45Ca2+ was also displaced from membranes by Mg2+ and Mn2+. Ca2+ had a biphasic effect on binding; low concentrations (1 to 10 muM) added to the incubation mixture stimulated binding, while higher concentrations (0.1 mM) caused inhibition. Mg2+ and Mn2+, at comparable concentrations, were also inhibitory, Na+ and K+ less so. In the case of Ca2+, both the stimulatory and inhibitory concentrations were lower than those required to achieve saturation of Ca2+-binding sites. Proteolytic enzymes (trypsin, alpha-chymotrypsin, and pronase) sharply reduced binding of 125I-TSH, owing to a decrease in receptor sites. Phospholipases A and C enhanced binding of TSH, while neuraminidase and beta-galactosidase were without measurable effect."} {"id": "PMID:181382", "title": "Mechanism and kinetics of the thermal activation of glucocorticoid hormone receptor complex.", "content": "Steroid-receptor complexes formed at low temperature and ionic strength do not bind to nuclei or chromatin. After a temporary exposure to high temperature, or ionic strength, or both, a fraction of them becomes activated (able to bind to nuclei). An assay of the activated form of the complex based upon titration with nuclei in excess was established. This assay was used to perform kinetic and equilibrium studies of the thermal activation of glucocorticoid-receptor complex in order to elucidate its mechanism. It was found that the reaction is of apparent first order and yields a monomolecular product. It thus probably consists of a conformational change in the steroid-receptor complex. The rate of activation is 1.37 +/- 0.06 X 10(-3) S-1 at 25 degrees. The free energy of thermodynamic activation (The word activation is used here in its usual thermodynamic meaning and not in the sense of receptor modification) of this reaction is greater than G = 21.3 Kcal. The corresponding enthalpy and entropy are respectively greater than H = 31.4 kcal and greater than S = 4 cal/degree. These positive and high values of greater than H and greater than S are very similar to those described for denaturation reactions of proteins suggesting that breakage of some noncovalent bonds could take place during activation. The reaction proceeds until approximately 60% of the complexes are activated. It was shown that this corresponds to an equilibrium between activated and nonactivated forms and not to the presence of a population of complexes unable to undergo activation. This equilibrium is not modified by temperature variations between 10 degrees and 30 degrees. It is possible to activate over 80% of the complexes when the activation is performed in the presence of excess acceptor, thus shifting the equilibrium. A similar situation is probably observed in situ in cells since 90% of the complexes are found in the nuclei when liver slices are incubated with hormone.", "contents": "Mechanism and kinetics of the thermal activation of glucocorticoid hormone receptor complex. Steroid-receptor complexes formed at low temperature and ionic strength do not bind to nuclei or chromatin. After a temporary exposure to high temperature, or ionic strength, or both, a fraction of them becomes activated (able to bind to nuclei). An assay of the activated form of the complex based upon titration with nuclei in excess was established. This assay was used to perform kinetic and equilibrium studies of the thermal activation of glucocorticoid-receptor complex in order to elucidate its mechanism. It was found that the reaction is of apparent first order and yields a monomolecular product. It thus probably consists of a conformational change in the steroid-receptor complex. The rate of activation is 1.37 +/- 0.06 X 10(-3) S-1 at 25 degrees. The free energy of thermodynamic activation (The word activation is used here in its usual thermodynamic meaning and not in the sense of receptor modification) of this reaction is greater than G = 21.3 Kcal. The corresponding enthalpy and entropy are respectively greater than H = 31.4 kcal and greater than S = 4 cal/degree. These positive and high values of greater than H and greater than S are very similar to those described for denaturation reactions of proteins suggesting that breakage of some noncovalent bonds could take place during activation. The reaction proceeds until approximately 60% of the complexes are activated. It was shown that this corresponds to an equilibrium between activated and nonactivated forms and not to the presence of a population of complexes unable to undergo activation. This equilibrium is not modified by temperature variations between 10 degrees and 30 degrees. It is possible to activate over 80% of the complexes when the activation is performed in the presence of excess acceptor, thus shifting the equilibrium. A similar situation is probably observed in situ in cells since 90% of the complexes are found in the nuclei when liver slices are incubated with hormone."} {"id": "PMID:181383", "title": "Submicrosomal localization of prolyl hydroxylase from chick embryo limb bone.", "content": "A fraction greatly enriched in microsomes was prepared from chick embryo limb bone tissue homogenates by differential centrifugation in a high density solution of Metrizamide. This fraction was used to determine the submicrosomal localization of prolyl hydroxylase. At a low concentration (0.05%) of the non-ionic detergents Triton X-100 and Brij-35, 90 to 93% of prolyl hydroxylase activity was released from microsomes. Concentrations of Triton X-100 greater than 0.1% were required to solubilize the intrinsic membrane enzyme NADH-ferricyanide reductase and to release membrane-bound ribosomes, while Brij-35 did not extensively solubilize membrane components even at concentrations up to 0.4%. In addition, prolyl hydroxylase activity which could subsequently be released from microsomes by Brij-35 was relatively resistant to trypsin proteolysis at concentrations which removed more than 50% of the ribosomes and approximately 40% of the protein from microsomes. These results suggest that 90 to 93% of prolyl hydroxylase activity in connective tissue is located within the cisternae of the endoplasmic reticulum. Gel filtration of prolyl hydroxylase released from microsomes or found in the soluble fraction of limb bone homogenates revealed two peaks of activity corresponding to molecular weights of 230,000 and 450,000 to 500,000. The latter is twice the value reported for purified chick embryo prolyl hydroxylase. A fraction of the total prolyl hydroxylase activity (generally 20 to 35%) in microsome preparations could be measured in the absence of detergent, although the microsomal membrane should be impermeable to the large unhydroxylated collagen chains used as substrate. On the basis of experimental data, it was concluded that detergent-independent activity was most likely due to damaged microsomal membranes and that this damage was sufficient to allow substrate and trypsin to enter the cisternae but not to allow prolyl hydroxylase to be released.", "contents": "Submicrosomal localization of prolyl hydroxylase from chick embryo limb bone. A fraction greatly enriched in microsomes was prepared from chick embryo limb bone tissue homogenates by differential centrifugation in a high density solution of Metrizamide. This fraction was used to determine the submicrosomal localization of prolyl hydroxylase. At a low concentration (0.05%) of the non-ionic detergents Triton X-100 and Brij-35, 90 to 93% of prolyl hydroxylase activity was released from microsomes. Concentrations of Triton X-100 greater than 0.1% were required to solubilize the intrinsic membrane enzyme NADH-ferricyanide reductase and to release membrane-bound ribosomes, while Brij-35 did not extensively solubilize membrane components even at concentrations up to 0.4%. In addition, prolyl hydroxylase activity which could subsequently be released from microsomes by Brij-35 was relatively resistant to trypsin proteolysis at concentrations which removed more than 50% of the ribosomes and approximately 40% of the protein from microsomes. These results suggest that 90 to 93% of prolyl hydroxylase activity in connective tissue is located within the cisternae of the endoplasmic reticulum. Gel filtration of prolyl hydroxylase released from microsomes or found in the soluble fraction of limb bone homogenates revealed two peaks of activity corresponding to molecular weights of 230,000 and 450,000 to 500,000. The latter is twice the value reported for purified chick embryo prolyl hydroxylase. A fraction of the total prolyl hydroxylase activity (generally 20 to 35%) in microsome preparations could be measured in the absence of detergent, although the microsomal membrane should be impermeable to the large unhydroxylated collagen chains used as substrate. On the basis of experimental data, it was concluded that detergent-independent activity was most likely due to damaged microsomal membranes and that this damage was sufficient to allow substrate and trypsin to enter the cisternae but not to allow prolyl hydroxylase to be released."} {"id": "PMID:181385", "title": "Secretion-related uptake of horseradish peroxidase in neurohypophysial axons.", "content": "During secretion of the neurohypophysial hormones, oxytocin and vasopressin, secretory granule membrane is added to the plasma membrane of the axon terminals. It is generally assumed that subsequent internalization of this additional membrane occurs by endocytosis. In order to study this process, we have traced the uptake of intravenously injected horseradish peroxidase by neurohypophysial axons in rats and golden hamsters. Peroxidase reaction product within the secretory axons was found mainly in vacuolar and C-shaped structures of a size comparable with or larger than the neurosecretory granules. Our observations suggest that these large horseradish peroxidase (HRP)-impregnated vacuoles arise directly by a form of macropinocytosis. Morphometric analysis indicated that this form of membrane retrieval increased significantly after the two types of stimuli used, reversible hemorrhage and electrical stimulation of the pituitary stalk. Microvesicular uptake of HRP was found to be comparatively less.", "contents": "Secretion-related uptake of horseradish peroxidase in neurohypophysial axons. During secretion of the neurohypophysial hormones, oxytocin and vasopressin, secretory granule membrane is added to the plasma membrane of the axon terminals. It is generally assumed that subsequent internalization of this additional membrane occurs by endocytosis. In order to study this process, we have traced the uptake of intravenously injected horseradish peroxidase by neurohypophysial axons in rats and golden hamsters. Peroxidase reaction product within the secretory axons was found mainly in vacuolar and C-shaped structures of a size comparable with or larger than the neurosecretory granules. Our observations suggest that these large horseradish peroxidase (HRP)-impregnated vacuoles arise directly by a form of macropinocytosis. Morphometric analysis indicated that this form of membrane retrieval increased significantly after the two types of stimuli used, reversible hemorrhage and electrical stimulation of the pituitary stalk. Microvesicular uptake of HRP was found to be comparatively less."} {"id": "PMID:181389", "title": "Quantitative in situ thin-layer chromatography of quinidine and salicylic acid in capillary blood.", "content": "A micro-method based on in situ thin-layer chromatography has been developed for the determination of quinidine and salicylic acid in 10-mu 1 samples of serum or plasma. The sample is applied directly to the silica gel layer without extraction, the proteins being precipitated on the chromatogram origin by means of ethanol. The chromatogram can be evaluated quantitatively by fluorescence scanning. Different pre-coated plates were investigated.", "contents": "Quantitative in situ thin-layer chromatography of quinidine and salicylic acid in capillary blood. A micro-method based on in situ thin-layer chromatography has been developed for the determination of quinidine and salicylic acid in 10-mu 1 samples of serum or plasma. The sample is applied directly to the silica gel layer without extraction, the proteins being precipitated on the chromatogram origin by means of ethanol. The chromatogram can be evaluated quantitatively by fluorescence scanning. Different pre-coated plates were investigated."} {"id": "PMID:181390", "title": "Studies of phenolic steroids in human subjects. XIX. Renal conjugation of 15alpha-hydroxyestradiol-3-sulfate.", "content": "In order to elucidate further the role of the kidney in the conjugation and excretion of 15alpha-hydroxy-estrogens, we synthesized doubly and singly labeled 15alpha-hydroxyestradiol-3-sulfate (15alpha-OHE-S) and determined its urinary excretory pattern after administering differently labeled 15alpha-OHE2-S into the renal artery and concomitantly into a peripheral vein and by the infusion of doubly labeled 3H-15alpha-OHE2-S-35S into the renal artery. The excretion of radioactivity in the early urinary samples and the conjugate pattern in these urines were determined. About twice as much radioactivity was excreted in the early urine samples originating from the renal artery injection than from samples obtained following peripheral administration, indicating renal conjugation and excretion of the 15alpha-OHE2-S. The latter was preponderantly excreted as the S-NAG with only a small part (about 10%) of the administered sulfate being hydrolyzed to the aglycone. The latter was then either conjugated with N-acetylglucosamine (NAG) or glucuronide, probably also in the kidney. Most of the 15-alpha-OHE2-S could not be accounted for, possibly because of biliary excretion and enterohepatic circulation. The results obtained and those already published indicate that the human kidney is capable of conjugating 15alpha-OHE2, its NAG, and its sulfate conjugates.", "contents": "Studies of phenolic steroids in human subjects. XIX. Renal conjugation of 15alpha-hydroxyestradiol-3-sulfate. In order to elucidate further the role of the kidney in the conjugation and excretion of 15alpha-hydroxy-estrogens, we synthesized doubly and singly labeled 15alpha-hydroxyestradiol-3-sulfate (15alpha-OHE-S) and determined its urinary excretory pattern after administering differently labeled 15alpha-OHE2-S into the renal artery and concomitantly into a peripheral vein and by the infusion of doubly labeled 3H-15alpha-OHE2-S-35S into the renal artery. The excretion of radioactivity in the early urinary samples and the conjugate pattern in these urines were determined. About twice as much radioactivity was excreted in the early urine samples originating from the renal artery injection than from samples obtained following peripheral administration, indicating renal conjugation and excretion of the 15alpha-OHE2-S. The latter was preponderantly excreted as the S-NAG with only a small part (about 10%) of the administered sulfate being hydrolyzed to the aglycone. The latter was then either conjugated with N-acetylglucosamine (NAG) or glucuronide, probably also in the kidney. Most of the 15-alpha-OHE2-S could not be accounted for, possibly because of biliary excretion and enterohepatic circulation. The results obtained and those already published indicate that the human kidney is capable of conjugating 15alpha-OHE2, its NAG, and its sulfate conjugates."} {"id": "PMID:181391", "title": "Aldosterone response to hypoglycemia: evidence of ACTH mediation.", "content": "Insulin-induced hypoglycemia caused an increase in plasma aldosterone as well as in renin activity and cortisol. After the suppression of the renin-angiotensin system by the prior administration of propranolol, insulin-induced hypoglycemia still caused a significant increase in plasma aldosterone similar to the increase in plasma cortisol, though plasma renin activity was suppressed. Conversely, after the suppression of endogenous ACTH by the prior admininstration of dexamethasone, insulin-induced hypoglycemia failed to induce a rise in plasma aldosterone and plasma cortisol, through plasma renin activity increased. The increase of plasma aldosterone in response to exogenous ACTH was not different with or without the prior administration of dexamethasone. We conclude that ACTH is largely responsible for the increased aldosterone secretion after insulin-induced hypoglycemia.", "contents": "Aldosterone response to hypoglycemia: evidence of ACTH mediation. Insulin-induced hypoglycemia caused an increase in plasma aldosterone as well as in renin activity and cortisol. After the suppression of the renin-angiotensin system by the prior administration of propranolol, insulin-induced hypoglycemia still caused a significant increase in plasma aldosterone similar to the increase in plasma cortisol, though plasma renin activity was suppressed. Conversely, after the suppression of endogenous ACTH by the prior admininstration of dexamethasone, insulin-induced hypoglycemia failed to induce a rise in plasma aldosterone and plasma cortisol, through plasma renin activity increased. The increase of plasma aldosterone in response to exogenous ACTH was not different with or without the prior administration of dexamethasone. We conclude that ACTH is largely responsible for the increased aldosterone secretion after insulin-induced hypoglycemia."} {"id": "PMID:181392", "title": "Specific metabolic pathways of steroid sulfates in human liver microsomes.", "content": "The hydroxylation of steroid sulfates has been studied in liver microsomal preparations from adult humans. Ten different C18, C19, and C21 steroid sulfates and the corresponding unconjugated steroids were used as substrates. In several cases it was found that steroid sulfates were efficiently hydroxylated in a way that differed both qualitatively and quantitatively from the hydroxylation of the corresponding unconjugated substrates. Only the hydrophobic (nonsulfurylated) end of the steroid sulfate molecule was hydroxylated. The steroids sulfurylated in position 3 were generally better substrates for the liver microsomal hydroxylase system than those sulfurylated in position 17. The findings that unconjugated and sulfoconjugated steroids are metabolized along different pathways in the liver may be of general significance. Sulfoconjugation and subsequent hydroxylation may also be an important pathway in the metabolism of xenobiotics in man.", "contents": "Specific metabolic pathways of steroid sulfates in human liver microsomes. The hydroxylation of steroid sulfates has been studied in liver microsomal preparations from adult humans. Ten different C18, C19, and C21 steroid sulfates and the corresponding unconjugated steroids were used as substrates. In several cases it was found that steroid sulfates were efficiently hydroxylated in a way that differed both qualitatively and quantitatively from the hydroxylation of the corresponding unconjugated substrates. Only the hydrophobic (nonsulfurylated) end of the steroid sulfate molecule was hydroxylated. The steroids sulfurylated in position 3 were generally better substrates for the liver microsomal hydroxylase system than those sulfurylated in position 17. The findings that unconjugated and sulfoconjugated steroids are metabolized along different pathways in the liver may be of general significance. Sulfoconjugation and subsequent hydroxylation may also be an important pathway in the metabolism of xenobiotics in man."} {"id": "PMID:181393", "title": "Comparison of prostaglandin E1 and TSH stimulation of cyclic AMP synthesis in thyroid tissues from euthyroid subjects and thyrotoxic patients.", "content": "Possible differences of the mode of action of TSH and prostaglandin E1 (PGE) on the synthesis of cyclic AMP were studied in normal human thyroids (normal thyroid) and thyroids from thyrotoxic patients (toxic thyroid). TSH was less effective in toxic thyroids than in normal thyroids; whereas PGE1 was equally effective in normal thyroids and toxic thyroids. Since the basal level of cyclic AMP was the same in normal and toxic thyroids, this lower sensitivity of toxic thyroids to TSH was not due to the fact that toxic thyroids were already overactive in terms of cyclic AMP synthesis. The measurement of adenylate cyclase and phosphodiesterase activities in the plasma membranes or homogenates failed to explain this lower sensitivity of toxic thyroids to TSH. Small and large doses of T4 and T3 failed to suppress an increase of cyclic AMP produced by PGE1, in the slices and plasma membranes of normal and toxic thyroids; whereas large doses of T3 depressed an increase of cyclic AMP in response to TSH in the thyroid plasma membrane of toxic thyroids. When both TSH and PGE1 were administered simultaneously, an additive increase of cyclic AMP was found in normal thyroids and in toxic thyroids. From the data accumulated, we suggest that, although TSH and PGE1 stimulate cyclic AMP synthesis in normal and toxic thyroids, the site of action and/or mode of action of these two stimulators may possibly be different, at least in human thyroids.", "contents": "Comparison of prostaglandin E1 and TSH stimulation of cyclic AMP synthesis in thyroid tissues from euthyroid subjects and thyrotoxic patients. Possible differences of the mode of action of TSH and prostaglandin E1 (PGE) on the synthesis of cyclic AMP were studied in normal human thyroids (normal thyroid) and thyroids from thyrotoxic patients (toxic thyroid). TSH was less effective in toxic thyroids than in normal thyroids; whereas PGE1 was equally effective in normal thyroids and toxic thyroids. Since the basal level of cyclic AMP was the same in normal and toxic thyroids, this lower sensitivity of toxic thyroids to TSH was not due to the fact that toxic thyroids were already overactive in terms of cyclic AMP synthesis. The measurement of adenylate cyclase and phosphodiesterase activities in the plasma membranes or homogenates failed to explain this lower sensitivity of toxic thyroids to TSH. Small and large doses of T4 and T3 failed to suppress an increase of cyclic AMP produced by PGE1, in the slices and plasma membranes of normal and toxic thyroids; whereas large doses of T3 depressed an increase of cyclic AMP in response to TSH in the thyroid plasma membrane of toxic thyroids. When both TSH and PGE1 were administered simultaneously, an additive increase of cyclic AMP was found in normal thyroids and in toxic thyroids. From the data accumulated, we suggest that, although TSH and PGE1 stimulate cyclic AMP synthesis in normal and toxic thyroids, the site of action and/or mode of action of these two stimulators may possibly be different, at least in human thyroids."} {"id": "PMID:181394", "title": "Unusual low plasma renin hypertension in a child.", "content": "A four-year-old girl with hypertension (140/60) and chronic hypokalemic alkalosis was studied to determine the origin of this clinical feature. High exchangeable sodium (56.7 meq/kg vs. 45-55 meq/kg in controls) was associated with a low plasma renin activity (6 ng/1/min vs. 26 +/- 3.1 in controls) and reduced aldosterone secretion rate (5.56 mug/day; normal: 50-150 mug per day)). A low corticosterone secretion rate (0.228 mg/day vs. 0.50-0.65 in controls) and urinary tetrahydrodeoxycorticosterone (0.007 mg/day vs. 0.03-0.09 mg/day in controls) were found. The basal secretion rate of cortisol was also low (1.80 mg/m2/day vs. 5.4-16.7 mg/m2/day in controls) in spite of normal plasma ACTH: 78 pg/ml. The normal increase of the cortisol secretion rate (from 1.80 to 65 mg/m2/day) after synthetic ACTH stimulation ruled out a 17 alpha hydroxylase deficiency. The low sweat Na/K ratio (0.25) and the good suppressing efficacy of dexamethasone and of the spironolactones on hypertension and on the hypokalemic alkalosis agreed with the hypersecretion of a mineralocorticoid. The secretion rate of 18 hydroxydeoxycorticosterone was high (91 mug/day/1.73 m2 vs. 40-80 mug per day and per 1.73 m2). As the mineralocorticoid potency of this steroid is weak, we speculate that it might be the precursor of a more potent but unknown mineralocorticoid which could influence the ACTH secretion.", "contents": "Unusual low plasma renin hypertension in a child. A four-year-old girl with hypertension (140/60) and chronic hypokalemic alkalosis was studied to determine the origin of this clinical feature. High exchangeable sodium (56.7 meq/kg vs. 45-55 meq/kg in controls) was associated with a low plasma renin activity (6 ng/1/min vs. 26 +/- 3.1 in controls) and reduced aldosterone secretion rate (5.56 mug/day; normal: 50-150 mug per day)). A low corticosterone secretion rate (0.228 mg/day vs. 0.50-0.65 in controls) and urinary tetrahydrodeoxycorticosterone (0.007 mg/day vs. 0.03-0.09 mg/day in controls) were found. The basal secretion rate of cortisol was also low (1.80 mg/m2/day vs. 5.4-16.7 mg/m2/day in controls) in spite of normal plasma ACTH: 78 pg/ml. The normal increase of the cortisol secretion rate (from 1.80 to 65 mg/m2/day) after synthetic ACTH stimulation ruled out a 17 alpha hydroxylase deficiency. The low sweat Na/K ratio (0.25) and the good suppressing efficacy of dexamethasone and of the spironolactones on hypertension and on the hypokalemic alkalosis agreed with the hypersecretion of a mineralocorticoid. The secretion rate of 18 hydroxydeoxycorticosterone was high (91 mug/day/1.73 m2 vs. 40-80 mug per day and per 1.73 m2). As the mineralocorticoid potency of this steroid is weak, we speculate that it might be the precursor of a more potent but unknown mineralocorticoid which could influence the ACTH secretion."} {"id": "PMID:181395", "title": "Rapid appearance of transient secondary adrenocortical insufficiency after alpha-particle radiation therapy for Cushing's disease.", "content": "A 17-year-old women received 12,000 rads of alpha-particle radiation for the treatment of Cushing's disease. One day after the completion of therapy, the patient developed nausea, vomiting, headache, and postural hypotension. Laboratory evaluation demonstrated a marked fall of the previously elevated urinary 17-hydroxycorticosteroids (17-OHCS) and undetectable plasma cortisols. The urinary 17-OHCS transiently returned to supranormal levels but over a 2 1/2-week period decreased and then remained low. The patient also demonstrated a subnormal urinary aldosterone excretion in relation to plasma renin activity (PRA) during 10 mEq/24 h sodium restriction. The remainder of the endocrine evaluation was normal, suggesting that pituitary function otherwise remained intact. One and one-half years after alpha-particle therapy, the patients's urinary 17-OHCS were normal and responded normally to metyrapone. The relationship between urinary aldosterone excretion and PRA also was normal. It is postulated that there was an infarction of an ACTH secreting pituitary tumor leaving the remainder of the pituitary intact. Achronically elevated circulating level of ACTH with sudden loss of ACTH secretion appeared to have been responsible for the initial low urinary aldosterone as well as the low urinary 17-OHCS. This is the first reported case of a presumed pituitary tumor infarction in association with alpha-particle pituitary radiation.", "contents": "Rapid appearance of transient secondary adrenocortical insufficiency after alpha-particle radiation therapy for Cushing's disease. A 17-year-old women received 12,000 rads of alpha-particle radiation for the treatment of Cushing's disease. One day after the completion of therapy, the patient developed nausea, vomiting, headache, and postural hypotension. Laboratory evaluation demonstrated a marked fall of the previously elevated urinary 17-hydroxycorticosteroids (17-OHCS) and undetectable plasma cortisols. The urinary 17-OHCS transiently returned to supranormal levels but over a 2 1/2-week period decreased and then remained low. The patient also demonstrated a subnormal urinary aldosterone excretion in relation to plasma renin activity (PRA) during 10 mEq/24 h sodium restriction. The remainder of the endocrine evaluation was normal, suggesting that pituitary function otherwise remained intact. One and one-half years after alpha-particle therapy, the patients's urinary 17-OHCS were normal and responded normally to metyrapone. The relationship between urinary aldosterone excretion and PRA also was normal. It is postulated that there was an infarction of an ACTH secreting pituitary tumor leaving the remainder of the pituitary intact. Achronically elevated circulating level of ACTH with sudden loss of ACTH secretion appeared to have been responsible for the initial low urinary aldosterone as well as the low urinary 17-OHCS. This is the first reported case of a presumed pituitary tumor infarction in association with alpha-particle pituitary radiation."} {"id": "PMID:181396", "title": "Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man.", "content": "The effect of metergoline, a specific antiserotoninergic drug, on ACTH secretion was investigated in 29 normal volunteers and in 4 patients with increased ACTH production (3 with Addison's disease, 1 with Cushing's disease). In 15 normal subjects, a 4-day treatment with 10 mg daily of metergoline significantly blunted the ACTH response to insulin hypoglycemia. Mean peak ACTH values before and after treatment were, respectively, 333 +/- 39.2 (SE) and 235 +/- 38.8 pg/ml (P less than 0.05). The corresponding values of plasma cortisol were 29.6 +/- 2.96 and 20.5 +/- 2.67 mug/100 ml (P less than 0.05). In contrast, metergoline failed to affect the ACTH response to lysine-vasopressin (LVP) administered iv (8 subjects studied) and im (6 subjects studied). In 3 patients suffering from Addison's disease, an appreciable although not statistically significant lowering of the plasma ACTH levels was noted during metergoline administration. The mean pre- and post-treatment values of plasma ACTH in these patients were, respectively, 1116 +/- 192.2 and 666 +/- 100.8 pg/ml, 4240 +/- 50.0 and 3398 +/- 368.0 pg/ml, and 431 +/- 44.0 and 352 +/- 23.9 pg/ml. In one patient with Cushing's disease caused by a pituitary adenoma, metergoline did not appreciably modify plasma ACTH levels. Taken together, these results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion. Moreover, they are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary.", "contents": "Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man. The effect of metergoline, a specific antiserotoninergic drug, on ACTH secretion was investigated in 29 normal volunteers and in 4 patients with increased ACTH production (3 with Addison's disease, 1 with Cushing's disease). In 15 normal subjects, a 4-day treatment with 10 mg daily of metergoline significantly blunted the ACTH response to insulin hypoglycemia. Mean peak ACTH values before and after treatment were, respectively, 333 +/- 39.2 (SE) and 235 +/- 38.8 pg/ml (P less than 0.05). The corresponding values of plasma cortisol were 29.6 +/- 2.96 and 20.5 +/- 2.67 mug/100 ml (P less than 0.05). In contrast, metergoline failed to affect the ACTH response to lysine-vasopressin (LVP) administered iv (8 subjects studied) and im (6 subjects studied). In 3 patients suffering from Addison's disease, an appreciable although not statistically significant lowering of the plasma ACTH levels was noted during metergoline administration. The mean pre- and post-treatment values of plasma ACTH in these patients were, respectively, 1116 +/- 192.2 and 666 +/- 100.8 pg/ml, 4240 +/- 50.0 and 3398 +/- 368.0 pg/ml, and 431 +/- 44.0 and 352 +/- 23.9 pg/ml. In one patient with Cushing's disease caused by a pituitary adenoma, metergoline did not appreciably modify plasma ACTH levels. Taken together, these results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion. Moreover, they are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary."} {"id": "PMID:181397", "title": "Thyroid antigen stimulates lymphocytes from patients with Graves' disease to produce thyroid-stimulating immunoglobulin (TSI).", "content": "Circulating lymphocytes from patients with Graves' disease and from control subjects were cultured in vitro alone, with normal human thyroid tissue homogenates, and with other nonthyroid human tissue homogenates. The supernatants of these cultures were assayed for human thyroid-stimulating activity by incubation with human thyroid slices in which increases in cAMP levels were then measured. Human thyroid stimulator activity was demonstrated in 16 out of 20 experiments in which lymphocytes from patients with active untreated Graves' disease (with hyperthyroidism) were cultured with normal thyroid homogenate, in 4 out of 17 experiments when control lymphocytes were similarly cultured, and in one out of 12 experiments in which the lymphocytes from the patients with Graves' disease were cultured with liver or gastric mucosa homogenate. Thyroid-stimulating activity was abolished by precipitation of the globulin from the supernatant by goat anti-human globulin serum. These results demonstrate that normal human thyroid tissue homogenates can specifically stimulate most lymphocytes from patients with Graves' disease and lymphocytes from a few normal subjects to produce human thyroid-stimulating immunoglobulins in vitro. This suggests that the human thyroid-stimulating immunoglobulins are auto-antibodies to normal thyroid constituents, but the possiblity that an antigenic change in the thyroid initiates the disease cannot be entirely excluded. The findings suggest that the prime change in Graves' disease is immunologic, perhaps a failure of immunological suppression.", "contents": "Thyroid antigen stimulates lymphocytes from patients with Graves' disease to produce thyroid-stimulating immunoglobulin (TSI). Circulating lymphocytes from patients with Graves' disease and from control subjects were cultured in vitro alone, with normal human thyroid tissue homogenates, and with other nonthyroid human tissue homogenates. The supernatants of these cultures were assayed for human thyroid-stimulating activity by incubation with human thyroid slices in which increases in cAMP levels were then measured. Human thyroid stimulator activity was demonstrated in 16 out of 20 experiments in which lymphocytes from patients with active untreated Graves' disease (with hyperthyroidism) were cultured with normal thyroid homogenate, in 4 out of 17 experiments when control lymphocytes were similarly cultured, and in one out of 12 experiments in which the lymphocytes from the patients with Graves' disease were cultured with liver or gastric mucosa homogenate. Thyroid-stimulating activity was abolished by precipitation of the globulin from the supernatant by goat anti-human globulin serum. These results demonstrate that normal human thyroid tissue homogenates can specifically stimulate most lymphocytes from patients with Graves' disease and lymphocytes from a few normal subjects to produce human thyroid-stimulating immunoglobulins in vitro. This suggests that the human thyroid-stimulating immunoglobulins are auto-antibodies to normal thyroid constituents, but the possiblity that an antigenic change in the thyroid initiates the disease cannot be entirely excluded. The findings suggest that the prime change in Graves' disease is immunologic, perhaps a failure of immunological suppression."} {"id": "PMID:181398", "title": "Thyroid peroxidase, thyroglobulin, cAMP and DNA in human thyroid.", "content": "Tissues from normal thyroid, euthyroid multinodular goiter, toxic goiter, Hashimoto's thyroiditis, thyroid adenoma, and carcinoma were examined for their content of deoxyribonucleic acid (DNA), thyroid peroxidase activity (TPA), thyroglobulin (TG), and adenosine 3',5'-cyclic monophosphate (cAMP). Compared with normal thyroids DNA was increased in the neoplastic tissues and decreased in euthyroid multinodular goiter. Quantitative changes of thyroglobulin were observed, especially in the thyroid tumors, and, in one case, immunoreactive 4S thyroglobulin-like protein was identified in the absence of 19S. TPA was grossly elevated in toxic goiter. This may be of significance in the pathogenesis of Graves' disease. TPA remained elevated even after adequate control of hyperthyroidism by preoperative PTU treatment. The cyclic AMP concentration in toxic goiter did not statistically differ from normal. This may indicate that extrathyroidal regulatory factors have a lesser role in the genesis and perpetuation of Graves' disease than otherwise believed. Cyclic AMP is known to exert a negative influence on tissue growth, and low concentrations in neoplasia have been reported. The values in the thyroid tumors studied were elevated, requiring further explanation.", "contents": "Thyroid peroxidase, thyroglobulin, cAMP and DNA in human thyroid. Tissues from normal thyroid, euthyroid multinodular goiter, toxic goiter, Hashimoto's thyroiditis, thyroid adenoma, and carcinoma were examined for their content of deoxyribonucleic acid (DNA), thyroid peroxidase activity (TPA), thyroglobulin (TG), and adenosine 3',5'-cyclic monophosphate (cAMP). Compared with normal thyroids DNA was increased in the neoplastic tissues and decreased in euthyroid multinodular goiter. Quantitative changes of thyroglobulin were observed, especially in the thyroid tumors, and, in one case, immunoreactive 4S thyroglobulin-like protein was identified in the absence of 19S. TPA was grossly elevated in toxic goiter. This may be of significance in the pathogenesis of Graves' disease. TPA remained elevated even after adequate control of hyperthyroidism by preoperative PTU treatment. The cyclic AMP concentration in toxic goiter did not statistically differ from normal. This may indicate that extrathyroidal regulatory factors have a lesser role in the genesis and perpetuation of Graves' disease than otherwise believed. Cyclic AMP is known to exert a negative influence on tissue growth, and low concentrations in neoplasia have been reported. The values in the thyroid tumors studied were elevated, requiring further explanation."} {"id": "PMID:181399", "title": "Systematic variables affecting simian virus 40-induced T-antigen expression and transformation in human cells.", "content": "Simian virus 40 (SV40) infection of human skin fibroblast and human tumor cells resulted in the expression of T-antigen and transformed foci. By examining various conditions of input virus multiplicity and initial cell density, the systematic variation of T-antigen determination was minimized. The most uniform results were obtained at multiplicities of about 275 plaque-forming units/cell. Within limits (5 X 10(4) to 2 X 10(5) cells/dish), initial cell density had little effect on T-antigen expression. Volume of virus inoculum was critical for some cell lines, but not for others. Cell passage level had no general effect on T-antigen expression, although specific cell lines demonstrated increased or decreased levels of T-antigen expression with serial passage for no apparent reason. T-antigen expression correlated with virus-induced cell transformation (focus formation) at two different multiplicities. In addition, T-antigen assays at 3 days gave consistently more reproducible results than transformation assays at 21 days in seven cell lines tested at two multiplicities of infection. These results defined input multiplicity as the major source of systematic variability and will permit development of a more reproducible tool in the evaluation of individuals at high risk of cancer.", "contents": "Systematic variables affecting simian virus 40-induced T-antigen expression and transformation in human cells. Simian virus 40 (SV40) infection of human skin fibroblast and human tumor cells resulted in the expression of T-antigen and transformed foci. By examining various conditions of input virus multiplicity and initial cell density, the systematic variation of T-antigen determination was minimized. The most uniform results were obtained at multiplicities of about 275 plaque-forming units/cell. Within limits (5 X 10(4) to 2 X 10(5) cells/dish), initial cell density had little effect on T-antigen expression. Volume of virus inoculum was critical for some cell lines, but not for others. Cell passage level had no general effect on T-antigen expression, although specific cell lines demonstrated increased or decreased levels of T-antigen expression with serial passage for no apparent reason. T-antigen expression correlated with virus-induced cell transformation (focus formation) at two different multiplicities. In addition, T-antigen assays at 3 days gave consistently more reproducible results than transformation assays at 21 days in seven cell lines tested at two multiplicities of infection. These results defined input multiplicity as the major source of systematic variability and will permit development of a more reproducible tool in the evaluation of individuals at high risk of cancer."} {"id": "PMID:181400", "title": "Detection of virus-specific immunoglobulins using a doubly labeled fluorescein-125I antibody.", "content": "Commercially prepared fluorescein-labeled antihuman antibodies were labed with 125I and used to compre specific herpes simplex virus antibody titers as determined by indirect fluorescent antibody and radioimmunoassay techniques. Total virus-specific immunoglobulin and virus-specific immunoglobulin G titers did not vary by more than one twofold dilution when compared by the two methods.", "contents": "Detection of virus-specific immunoglobulins using a doubly labeled fluorescein-125I antibody. Commercially prepared fluorescein-labeled antihuman antibodies were labed with 125I and used to compre specific herpes simplex virus antibody titers as determined by indirect fluorescent antibody and radioimmunoassay techniques. Total virus-specific immunoglobulin and virus-specific immunoglobulin G titers did not vary by more than one twofold dilution when compared by the two methods."} {"id": "PMID:181401", "title": "Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease.", "content": "Contact between human neutrophils and aggregated immunoglobulin G bound to micropore filters has been studied as a model of the pathogenesis of tissue damage in immune complex disease. Contact with this surface, as well as with plain filters and polystyrene petri dishes, induced neutrophils to elaborate superoxide anion and hydrogen peroxide and to generate chemiluminescence, which has been attributed to singlet oxygen. Pretreatment of the cells with cytochalasin B decreased these activities but increased release of lysosomal beta-glucuronidase, suggesting that degranulation and the burst of oxygen metabolism that characterizes phagocytes are independently regulated functions. Toxic oxygen metabolites released from neutrophils are highly reactive and could mediate tissue injury at sites of inflammation.", "contents": "Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. Contact between human neutrophils and aggregated immunoglobulin G bound to micropore filters has been studied as a model of the pathogenesis of tissue damage in immune complex disease. Contact with this surface, as well as with plain filters and polystyrene petri dishes, induced neutrophils to elaborate superoxide anion and hydrogen peroxide and to generate chemiluminescence, which has been attributed to singlet oxygen. Pretreatment of the cells with cytochalasin B decreased these activities but increased release of lysosomal beta-glucuronidase, suggesting that degranulation and the burst of oxygen metabolism that characterizes phagocytes are independently regulated functions. Toxic oxygen metabolites released from neutrophils are highly reactive and could mediate tissue injury at sites of inflammation."} {"id": "PMID:181402", "title": "The effects of spontaneous obesity on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.", "content": "We have studied insulin, binding, glucose transport, and glucose oxidation, using large adipocytes isolated from older, fatter rats (greater than 12-mo-old, greater than 550 g), and smaller cells obtained from younger, leaner animals (4-5-wk-old, 120-160 g). At media glucose levels less than 5 mM, basal (absence of insulin) rates of glucose oxidation are comparable in both groups of cells. However, in the presence of insulin, the increase in glucose oxidation is much greater in the smaller cells. Maximally effective insulin levels could not overcome the defect in glucose oxidation by larger cells, and thus, even though studies of insulin binding demonstrated a 30-40% decrease in insulin receptors on the larger cells, it is probable that the defect in glucose oxidation is distal to the insulin receptor. Glucose transport was assessed by direct measurement of 2-deoxy glucose uptake. Basal levels of uptake were greater for the larger cells, whereas at maximally effective insulin concentrations, rates of 2-deoxy glucose uptake were the same for both groups of cells. Thus, in the presence of maximally effective levels of insulin, the apparent Km (2.3-2.7 mM) and Vmax values (2.6 and 2.7 nmol/10(5) cells per min) of 2-deoxy glucose uptake were comparable, indicating that the glucose transport system of the larger cells was intact. However, at submaximal levels of insulin, small adipocytes took up more 2-deoxy glucose than larger cells. These findings represent a rightward shift in the insulin dose-response curve in the cells from the older, fatter animals, and this is the predicted functional sequelae of the observed decrease in insulin receptors. Finally, when the amount of insulin bound was plotted as a function of 2-deoxy glucose uptake, no difference was seen between both groups of cells. This indicates that coupling between insulin receptor complexes and the glucose transport system is intact in large adipocytes, and is further evidence that a defect(s) in intracellular glucose metabolism is responsible for the decrease in glucose oxidation of adipocytes from older, fatter rats. (a) insulin-mediated glucose oxidation is markedly decreased in large adipocytes from older, fatter rats, and since this decrease cannot be corrected by maximally effective insulin levels, the defect is probably distal to the insulin receptor; (b) the glucose transport system is basically normal in large adipocytes; (c) insulin binding to receptors is decreased in large cells and the functional sequelae of this decrease in insulin binding i.e., a rightward shift in the insulin dose-response curve for 2-deoxy glucose uptake, was observed, and (d) since the decreased rates of insulin-mediated glucose oxidation can not be attributed to changes in insulin receptors or to changes in glucose transport, an intracellular defect in glucose metabolism is suggested.", "contents": "The effects of spontaneous obesity on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes. We have studied insulin, binding, glucose transport, and glucose oxidation, using large adipocytes isolated from older, fatter rats (greater than 12-mo-old, greater than 550 g), and smaller cells obtained from younger, leaner animals (4-5-wk-old, 120-160 g). At media glucose levels less than 5 mM, basal (absence of insulin) rates of glucose oxidation are comparable in both groups of cells. However, in the presence of insulin, the increase in glucose oxidation is much greater in the smaller cells. Maximally effective insulin levels could not overcome the defect in glucose oxidation by larger cells, and thus, even though studies of insulin binding demonstrated a 30-40% decrease in insulin receptors on the larger cells, it is probable that the defect in glucose oxidation is distal to the insulin receptor. Glucose transport was assessed by direct measurement of 2-deoxy glucose uptake. Basal levels of uptake were greater for the larger cells, whereas at maximally effective insulin concentrations, rates of 2-deoxy glucose uptake were the same for both groups of cells. Thus, in the presence of maximally effective levels of insulin, the apparent Km (2.3-2.7 mM) and Vmax values (2.6 and 2.7 nmol/10(5) cells per min) of 2-deoxy glucose uptake were comparable, indicating that the glucose transport system of the larger cells was intact. However, at submaximal levels of insulin, small adipocytes took up more 2-deoxy glucose than larger cells. These findings represent a rightward shift in the insulin dose-response curve in the cells from the older, fatter animals, and this is the predicted functional sequelae of the observed decrease in insulin receptors. Finally, when the amount of insulin bound was plotted as a function of 2-deoxy glucose uptake, no difference was seen between both groups of cells. This indicates that coupling between insulin receptor complexes and the glucose transport system is intact in large adipocytes, and is further evidence that a defect(s) in intracellular glucose metabolism is responsible for the decrease in glucose oxidation of adipocytes from older, fatter rats. (a) insulin-mediated glucose oxidation is markedly decreased in large adipocytes from older, fatter rats, and since this decrease cannot be corrected by maximally effective insulin levels, the defect is probably distal to the insulin receptor; (b) the glucose transport system is basically normal in large adipocytes; (c) insulin binding to receptors is decreased in large cells and the functional sequelae of this decrease in insulin binding i.e., a rightward shift in the insulin dose-response curve for 2-deoxy glucose uptake, was observed, and (d) since the decreased rates of insulin-mediated glucose oxidation can not be attributed to changes in insulin receptors or to changes in glucose transport, an intracellular defect in glucose metabolism is suggested."} {"id": "PMID:181403", "title": "A 25-hydroxylation pathway of cholic acid biosynthesis in man and rat.", "content": "This paper describes a pathway of cholic acid synthesis, in man and in the rat, which involves 25-hydroxylated intermediates and is catalyzed by microsomal and soluble enzymes. The subcellular localization, stereospecificity, and other properties of the enzymes involved were studied with liver fractions of normolipidemic subjects, cerebrotendinous xanthomatosis patients, and rats. 5beta-Cholestane-3alpha,7alpha,12alpha,25-tetrol was converted to 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol by the microsomal fraction in the presence of NADPH and O2. 5beta-Cholestane-3alpha,7alpha,12alpha,24alpha,25-pentol, 5beta-cholestane-3alpha,7alpha,12alpha,-23xi,25-pentol, and 5beta-cholestane-3alpha,7alpha,12alpha,25,26-pentol were also formed. In the presence of NAD, 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol, but not the other 5beta-cholestanepentols formed, was converted to cholic acid by soluble enzymes in good yield. These experiments demonstrate the existence of a pathway for side-chain degradation in cholic acid synthesis which does not involve hydroxylation at C-26 or the participation of mitochondria.", "contents": "A 25-hydroxylation pathway of cholic acid biosynthesis in man and rat. This paper describes a pathway of cholic acid synthesis, in man and in the rat, which involves 25-hydroxylated intermediates and is catalyzed by microsomal and soluble enzymes. The subcellular localization, stereospecificity, and other properties of the enzymes involved were studied with liver fractions of normolipidemic subjects, cerebrotendinous xanthomatosis patients, and rats. 5beta-Cholestane-3alpha,7alpha,12alpha,25-tetrol was converted to 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol by the microsomal fraction in the presence of NADPH and O2. 5beta-Cholestane-3alpha,7alpha,12alpha,24alpha,25-pentol, 5beta-cholestane-3alpha,7alpha,12alpha,-23xi,25-pentol, and 5beta-cholestane-3alpha,7alpha,12alpha,25,26-pentol were also formed. In the presence of NAD, 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol, but not the other 5beta-cholestanepentols formed, was converted to cholic acid by soluble enzymes in good yield. These experiments demonstrate the existence of a pathway for side-chain degradation in cholic acid synthesis which does not involve hydroxylation at C-26 or the participation of mitochondria."} {"id": "PMID:181404", "title": "Effect of aspirin on normal and cholera toxin-stimulated intestinal electrolyte transport.", "content": "The effect of aspirin on normal and cholera toxin-stimulated electrolyte transport has been investigated in vitro, because this drug appears to inhibit cholera toxin-induced intestinal secretion in in vivo animal models. In the Ussing chamber, 10 mM aspirin decreased the control rabbit ileal potential difference and short-circuit current by 50% and increased conductance by 28%. Bidirectional electrolyte flux determinations showed that aspirin significantly increased both Na and Cl absorption and reduced flux (which probably represents HCO3 secretion) to zero. This effect of aspirin appears to be identical to that reported to others with catecholamines as determined with similar techniques. However, alpha-adrenergic blockers did not prevent the electrical effects of aspirin, suggesting that aspirin does not have its effect through release of tissue stores of catecholamines. In the presence of aspirin, cholera toxin increased the potential difference and short-circuit current, and decreased the conductance of rabbit ileum in a fashion qualitatively similar to control tissues. However, aspirin reversed cholera toxin-stimulated Na transport from secretion to absorption, inhibited cholera toxin, induced Cl secretion by 58% and partially, but not significantly, inhibited HCO3 secretion. Thus, the inhibitory effect of aspirin on cholera toxin-induced electrolyte secretion appears to be due to aspirin-stimulated Na and Cl absorption. Although aspirin reduced tissue cyclic AMP concentrations in normal and cholera toxin-stimulated ileum, it also inhibited the electrolyte secretion induced by exogenous cyclic AMP. Thus, if aspirin's stimulatory effect on sodium and anion absorption in normal tissue and its inhibitory effect on cholera toxin-stimulated sodium and anion secretion involves a cyclic AMP-mediated system, the effect must be a step distal to cyclic AMP production or degradation. The exact mechanism of aspirin's effect on normal and cholera toxin-induced electrolyte transport, and its possible usefulness in the treatment of cholera diarrhea, remains to be determined.", "contents": "Effect of aspirin on normal and cholera toxin-stimulated intestinal electrolyte transport. The effect of aspirin on normal and cholera toxin-stimulated electrolyte transport has been investigated in vitro, because this drug appears to inhibit cholera toxin-induced intestinal secretion in in vivo animal models. In the Ussing chamber, 10 mM aspirin decreased the control rabbit ileal potential difference and short-circuit current by 50% and increased conductance by 28%. Bidirectional electrolyte flux determinations showed that aspirin significantly increased both Na and Cl absorption and reduced flux (which probably represents HCO3 secretion) to zero. This effect of aspirin appears to be identical to that reported to others with catecholamines as determined with similar techniques. However, alpha-adrenergic blockers did not prevent the electrical effects of aspirin, suggesting that aspirin does not have its effect through release of tissue stores of catecholamines. In the presence of aspirin, cholera toxin increased the potential difference and short-circuit current, and decreased the conductance of rabbit ileum in a fashion qualitatively similar to control tissues. However, aspirin reversed cholera toxin-stimulated Na transport from secretion to absorption, inhibited cholera toxin, induced Cl secretion by 58% and partially, but not significantly, inhibited HCO3 secretion. Thus, the inhibitory effect of aspirin on cholera toxin-induced electrolyte secretion appears to be due to aspirin-stimulated Na and Cl absorption. Although aspirin reduced tissue cyclic AMP concentrations in normal and cholera toxin-stimulated ileum, it also inhibited the electrolyte secretion induced by exogenous cyclic AMP. Thus, if aspirin's stimulatory effect on sodium and anion absorption in normal tissue and its inhibitory effect on cholera toxin-stimulated sodium and anion secretion involves a cyclic AMP-mediated system, the effect must be a step distal to cyclic AMP production or degradation. The exact mechanism of aspirin's effect on normal and cholera toxin-induced electrolyte transport, and its possible usefulness in the treatment of cholera diarrhea, remains to be determined."} {"id": "PMID:181405", "title": "Differences in the attenuation of ultrasound by normal, benign, and malignant breast tissue.", "content": "In quantitative measurements of the attenuation of ultrasound in 18 samples of variously normal, benign, and malignant breast tissue, we found significantly different ranges of attenuation. As observed in previous in vivo studies, with the exception of medullary carcinoma, malignant tissue produces the most attentuation of ultrasound in the frequency range of 1.5 to 3.0 MHz we employed. The apparatus, measurement method, results, and the possible causes of the differences in attenuation are presented.", "contents": "Differences in the attenuation of ultrasound by normal, benign, and malignant breast tissue. In quantitative measurements of the attenuation of ultrasound in 18 samples of variously normal, benign, and malignant breast tissue, we found significantly different ranges of attenuation. As observed in previous in vivo studies, with the exception of medullary carcinoma, malignant tissue produces the most attentuation of ultrasound in the frequency range of 1.5 to 3.0 MHz we employed. The apparatus, measurement method, results, and the possible causes of the differences in attenuation are presented."} {"id": "PMID:181409", "title": "Comparison of binding proteins of glucocorticoids in mammary tissue and in blood sera from lactating cows.", "content": "Supernatant fractions (700 X g) isolated from homogenates of mammary tissue slices from three lactating Holstein cows (slices previously incubated with [hydrogen-3] cortisol for 1 h at 37 C) were electrophoresed on 7% polyacrylamide gels. The majority of radioactivity was in a protein(s) 2.5 to 3 cm from the origin whereas bovine serum incubated with [hydrogen-3] cortisol showed the majority of radioactivity in a protein 5 to 6 cm from the origin. N,N-diethylaminoethyl cellulose chromatography of 700 X g supernatant fluids from three lactating cows revealed that [hydrogen-3] cortisol was associated with a protein component that eluted with .3 M potassium phosphate, pH 8.0. In contrast, [hydrogen-3] cortisol bound to bovine sera eluted as two protein components with .05 and .1 M potassium phosphate, pH 8.0. Approximate molecular weights determined from gel filtration (four lactating cows) and sucrose density studies (two lactating cows) were estimated to be 2.5 X 10(5) to 3 X 10(6) for the 700 X g mammary receptor of cortisol and 6 X 10)4) to 8 X 10(4) for the primary protein which binds cortisol in serum. We conclude that lactating bovine mammary tissue contains a protein(s) capable of binding tritiated cortisol which is unique from the corticosteroid binding proteins of blood.", "contents": "Comparison of binding proteins of glucocorticoids in mammary tissue and in blood sera from lactating cows. Supernatant fractions (700 X g) isolated from homogenates of mammary tissue slices from three lactating Holstein cows (slices previously incubated with [hydrogen-3] cortisol for 1 h at 37 C) were electrophoresed on 7% polyacrylamide gels. The majority of radioactivity was in a protein(s) 2.5 to 3 cm from the origin whereas bovine serum incubated with [hydrogen-3] cortisol showed the majority of radioactivity in a protein 5 to 6 cm from the origin. N,N-diethylaminoethyl cellulose chromatography of 700 X g supernatant fluids from three lactating cows revealed that [hydrogen-3] cortisol was associated with a protein component that eluted with .3 M potassium phosphate, pH 8.0. In contrast, [hydrogen-3] cortisol bound to bovine sera eluted as two protein components with .05 and .1 M potassium phosphate, pH 8.0. Approximate molecular weights determined from gel filtration (four lactating cows) and sucrose density studies (two lactating cows) were estimated to be 2.5 X 10(5) to 3 X 10(6) for the 700 X g mammary receptor of cortisol and 6 X 10)4) to 8 X 10(4) for the primary protein which binds cortisol in serum. We conclude that lactating bovine mammary tissue contains a protein(s) capable of binding tritiated cortisol which is unique from the corticosteroid binding proteins of blood."} {"id": "PMID:181412", "title": "Toluene diisocyanate (TDI) pulmonary disease: immunologic and inhalation challenge studies.", "content": "Clinical and serologic effects of TDI exposure were studied in 112 occupationally exposed plant workers. Sera were obtained before and after commencement of TDI production. All subjects were skin-tested with common inhalant allergens and a TDI-HSA conjugate. Total eosinophil counts, immunoglobulin quantitations, and specific antibody assays by PCA, P-K, and radioimmunoassay were performed. Clinically \"sensitive\" individuals were tested by provocative inhalation challenge with from 0.005 ppm to the threshold limit value of 0.02 ppm TDI. No TDI-induced immunologic changes were noted with the exception of 3 individuals who demonstrated small positive wheal-and-erythema reactions to TDI-HSA but not to HSA alone. Inhalation challenge with TDI vapor produced airways obstruction, as measured by FEF (25-75). These responses were of the immediate, delayed, and dual type, and were provoked in some cases with levels as low as 0.005 ppm TDI.", "contents": "Toluene diisocyanate (TDI) pulmonary disease: immunologic and inhalation challenge studies. Clinical and serologic effects of TDI exposure were studied in 112 occupationally exposed plant workers. Sera were obtained before and after commencement of TDI production. All subjects were skin-tested with common inhalant allergens and a TDI-HSA conjugate. Total eosinophil counts, immunoglobulin quantitations, and specific antibody assays by PCA, P-K, and radioimmunoassay were performed. Clinically \"sensitive\" individuals were tested by provocative inhalation challenge with from 0.005 ppm to the threshold limit value of 0.02 ppm TDI. No TDI-induced immunologic changes were noted with the exception of 3 individuals who demonstrated small positive wheal-and-erythema reactions to TDI-HSA but not to HSA alone. Inhalation challenge with TDI vapor produced airways obstruction, as measured by FEF (25-75). These responses were of the immediate, delayed, and dual type, and were provoked in some cases with levels as low as 0.005 ppm TDI."} {"id": "PMID:181413", "title": "Polyunsaturated meat and dairy products in fat-modified food patterns for hyperlipidemia.", "content": "Polyunsaturated meat and dairy products were compared with their saturated counterparts to determine their usefulness in a fat-modified diet for hyperlipidemic persons and their spouses. These polyunsaturated animal products were produced by feeding cattle a supplement of oil droplets coated with denatured protein. As a result, the polyunsaturated fatty acid content was 27 to 28 per cent of the meat fat and butterfat; saturated fatty acids (C12:0 to tc16:0) were 18 to 19 per cent. Of the eleven free-living subjects three were normocholesteremic, three had type IIa hyperlipidemia and five had type VI (IIb). In the fourteen-week study, an adjustment period of three weeks was followed by two consecutive experimental periods of four weeks each, then by a three-week follow-up period. During the adjustment period, participants continued to follow their usual eating patterns. During both experimental periods all followed the same prescribed fat modified food pattern using polyunsaturated margarine and oil. Five participants ate polyunsaturated beef and dairy products during the first experimental period and their saturated counterparts in the second; six participants ate saturated products first, then polyunsaturated. During the follow-up period, all participants selected all their own food. Serum cholesterol levels in five participants who had not previously followed a fat-modified diet were reduced by 18 per cent with polyunsaturated animal products and 11 per cent with saturated products. Serum cholesterol in six participants, previously on a fat-modified diet, was not significantly changed with polyunsaturated products. In ten of eleven participants, serum cholesterol levels were an average of 6 per cent lower with polyunsaturated products than with saturated products. It is concluded that polyunsaturated animal products are suitable for use in fat-modified food patterns for reducing hyperlipidemia, with some restrictions in the amount of polyunsaturated animal fat and with the inclusion of polyunsaturated oil and margarine.", "contents": "Polyunsaturated meat and dairy products in fat-modified food patterns for hyperlipidemia. Polyunsaturated meat and dairy products were compared with their saturated counterparts to determine their usefulness in a fat-modified diet for hyperlipidemic persons and their spouses. These polyunsaturated animal products were produced by feeding cattle a supplement of oil droplets coated with denatured protein. As a result, the polyunsaturated fatty acid content was 27 to 28 per cent of the meat fat and butterfat; saturated fatty acids (C12:0 to tc16:0) were 18 to 19 per cent. Of the eleven free-living subjects three were normocholesteremic, three had type IIa hyperlipidemia and five had type VI (IIb). In the fourteen-week study, an adjustment period of three weeks was followed by two consecutive experimental periods of four weeks each, then by a three-week follow-up period. During the adjustment period, participants continued to follow their usual eating patterns. During both experimental periods all followed the same prescribed fat modified food pattern using polyunsaturated margarine and oil. Five participants ate polyunsaturated beef and dairy products during the first experimental period and their saturated counterparts in the second; six participants ate saturated products first, then polyunsaturated. During the follow-up period, all participants selected all their own food. Serum cholesterol levels in five participants who had not previously followed a fat-modified diet were reduced by 18 per cent with polyunsaturated animal products and 11 per cent with saturated products. Serum cholesterol in six participants, previously on a fat-modified diet, was not significantly changed with polyunsaturated products. In ten of eleven participants, serum cholesterol levels were an average of 6 per cent lower with polyunsaturated products than with saturated products. It is concluded that polyunsaturated animal products are suitable for use in fat-modified food patterns for reducing hyperlipidemia, with some restrictions in the amount of polyunsaturated animal fat and with the inclusion of polyunsaturated oil and margarine."} {"id": "PMID:181420", "title": "Immunoreactive corticotrophin reserve in old age in man during and after surgical stress.", "content": "Attempts have been made to establish whether the immunoreactive corticotrophin (IR-ACTH) reserve was impaired in old age during surgical stress and whether an exhaustion of the IR-ACTH reserve could be traced postoperatively. Recognition of the degenerative changes of the senescent adenohypophysis has made this investigation essential in an effort to analyze factors responsible for the high risk involved in surgery on the aged. In the study 18 young and 14 elderly patients were subjected to elective abdominal or thoracic surgery, and the IR-ACTH response was determined. No significant age-related difference in response to surgery was found. On the 5th day after operation an intravenous metyrapone test was carried out, and the IR-ACTH response in plasma determined. In the elderly, the IR-ACTH response to metyrapone was not found to be inferior to that in the young patients. It was concluded that the IR-ACTH reserve was unimpaired during surgery in old age and that exhaustion was not in evidence based on unimpaired IR-ACTH response during repeated stress in the postoperative period. Therefore, decreased ACTH reserve seems not to be a factor involved in the higher surgical risk in the elderly.", "contents": "Immunoreactive corticotrophin reserve in old age in man during and after surgical stress. Attempts have been made to establish whether the immunoreactive corticotrophin (IR-ACTH) reserve was impaired in old age during surgical stress and whether an exhaustion of the IR-ACTH reserve could be traced postoperatively. Recognition of the degenerative changes of the senescent adenohypophysis has made this investigation essential in an effort to analyze factors responsible for the high risk involved in surgery on the aged. In the study 18 young and 14 elderly patients were subjected to elective abdominal or thoracic surgery, and the IR-ACTH response was determined. No significant age-related difference in response to surgery was found. On the 5th day after operation an intravenous metyrapone test was carried out, and the IR-ACTH response in plasma determined. In the elderly, the IR-ACTH response to metyrapone was not found to be inferior to that in the young patients. It was concluded that the IR-ACTH reserve was unimpaired during surgery in old age and that exhaustion was not in evidence based on unimpaired IR-ACTH response during repeated stress in the postoperative period. Therefore, decreased ACTH reserve seems not to be a factor involved in the higher surgical risk in the elderly."} {"id": "PMID:181422", "title": "[Prevention of the malignant form of trophoblastic disease after a hydatidiform mole: systematic or selective chemotherapy].", "content": "After a mole has been evacuated there are two ways of treating the condition: routine chemotherapy from the beginning or chemotherapy reserved for selected cases. They offer the same chances of cure. Seeing that the risk of malignancy in our country is 5 per cent and that selective chemotherapy only exposes a small number of patients to the risk of such treatment, we have adopted the scheme of follow-up suggested by Bagshawe and recommended by OERTC. The follow-up is based on radio-immune assay for HCG carried out at regular intervals for two years. Only cases where the level of HCG is higher than 25,000 international units per litre, one month after curettage, or cases where the rise in HCG is associated with metastases, are treated with chemotherapy. In our experience, which is based on 20 cases, we acknowledge the value of radio-immune assaying. It is superior to immunological tests used for pregnancy diagnosis in sensitivity. It also appears to us that systematic treatment routinely administered and treatment based on raised levels of HCG two months after evacuation of a mole are useless. Only 3 cases were treated with chemotherapy out of the 20 cases that were followed up. We have had no malignancy after 2 and 3 years of checking back on the patients. Treatment given routinely from the start would have been unnecessary exposure to the risks of chemotherapy for 17 patients. Had we taken into account the abnormal rise in HCG after 8 weeks we would still have treated 7 patients instead of 3 with the same results as far as cure. We have worked out a graph for the drop in the levels of HCG after a mole has been evacuated. This may serve as a base for criteria for treatment in the future. Cases where the levels of HCG are above the 95 percentile are considered as at risk to evolve into malignant forms of disease. Consequently earlier treatment can be started (before the 6th month) without altering the number of patients who are going to be treated.", "contents": "[Prevention of the malignant form of trophoblastic disease after a hydatidiform mole: systematic or selective chemotherapy]. After a mole has been evacuated there are two ways of treating the condition: routine chemotherapy from the beginning or chemotherapy reserved for selected cases. They offer the same chances of cure. Seeing that the risk of malignancy in our country is 5 per cent and that selective chemotherapy only exposes a small number of patients to the risk of such treatment, we have adopted the scheme of follow-up suggested by Bagshawe and recommended by OERTC. The follow-up is based on radio-immune assay for HCG carried out at regular intervals for two years. Only cases where the level of HCG is higher than 25,000 international units per litre, one month after curettage, or cases where the rise in HCG is associated with metastases, are treated with chemotherapy. In our experience, which is based on 20 cases, we acknowledge the value of radio-immune assaying. It is superior to immunological tests used for pregnancy diagnosis in sensitivity. It also appears to us that systematic treatment routinely administered and treatment based on raised levels of HCG two months after evacuation of a mole are useless. Only 3 cases were treated with chemotherapy out of the 20 cases that were followed up. We have had no malignancy after 2 and 3 years of checking back on the patients. Treatment given routinely from the start would have been unnecessary exposure to the risks of chemotherapy for 17 patients. Had we taken into account the abnormal rise in HCG after 8 weeks we would still have treated 7 patients instead of 3 with the same results as far as cure. We have worked out a graph for the drop in the levels of HCG after a mole has been evacuated. This may serve as a base for criteria for treatment in the future. Cases where the levels of HCG are above the 95 percentile are considered as at risk to evolve into malignant forms of disease. Consequently earlier treatment can be started (before the 6th month) without altering the number of patients who are going to be treated."} {"id": "PMID:181489", "title": "Histochemical localization of potassium-stimulated P-nitrophenylphosphatase activity in the somatosensory cortex of the rat.", "content": "Potassium-stimulated p-nitrophenylphosphatase (K+-pNPPase) activity was investigated in rat somatosensory cortex where 64-88% of enzymatic activity survived 5-10 min of fixation with 3% formaldehyde in 0.1 M cacodylate buffer, pH 7.4. Potassium-stimulated activity was inhibited by 1-10 mM ouabain. Levamisole (1.7 mM) inhibited brain alkaline phosphatase activity, facilitating the detection of K+-pNPPase activity. Strontium (10-20 mM) inhibited enzymatic activity by 38-75%. In parallel histochemical studies reaction product was found in strata, with cortical layers 2, 3, 4 and the outer portion of 5 containing the heaviest deposits. Highly reactive, vertically oriented, large diameter fibers were seen as groups between the outer portion of layer 5 and the pail surface. These fibers apparently arborize in the superficial layers. Smaller fibers were also positive and were oriented in various planes. The highest density of smaller, positive fibers occurred in layers 2 through 5. All positive fibers appeared to be axons or dendrites. Reaction product was not heavily concentrated in neuron perikarya or in glial elements. Sections did not contain reaction product when incubated in media lacking K+ or containing ouabain. The convergence of data from parallel histochemical and biochemical approaches supports the conclusion that the reactivity localized in the cerebral cortex represented the site of K+-pNPPase, a known component of the Na+,K+-adenosine triphosphatase complex. Neuronal processes demonstrated the highest enzymatic activity and may be most important in the active transport of Na+ and K+ in somatosensory cortex.", "contents": "Histochemical localization of potassium-stimulated P-nitrophenylphosphatase activity in the somatosensory cortex of the rat. Potassium-stimulated p-nitrophenylphosphatase (K+-pNPPase) activity was investigated in rat somatosensory cortex where 64-88% of enzymatic activity survived 5-10 min of fixation with 3% formaldehyde in 0.1 M cacodylate buffer, pH 7.4. Potassium-stimulated activity was inhibited by 1-10 mM ouabain. Levamisole (1.7 mM) inhibited brain alkaline phosphatase activity, facilitating the detection of K+-pNPPase activity. Strontium (10-20 mM) inhibited enzymatic activity by 38-75%. In parallel histochemical studies reaction product was found in strata, with cortical layers 2, 3, 4 and the outer portion of 5 containing the heaviest deposits. Highly reactive, vertically oriented, large diameter fibers were seen as groups between the outer portion of layer 5 and the pail surface. These fibers apparently arborize in the superficial layers. Smaller fibers were also positive and were oriented in various planes. The highest density of smaller, positive fibers occurred in layers 2 through 5. All positive fibers appeared to be axons or dendrites. Reaction product was not heavily concentrated in neuron perikarya or in glial elements. Sections did not contain reaction product when incubated in media lacking K+ or containing ouabain. The convergence of data from parallel histochemical and biochemical approaches supports the conclusion that the reactivity localized in the cerebral cortex represented the site of K+-pNPPase, a known component of the Na+,K+-adenosine triphosphatase complex. Neuronal processes demonstrated the highest enzymatic activity and may be most important in the active transport of Na+ and K+ in somatosensory cortex."} {"id": "PMID:181490", "title": "Cellular immunity in chronic Theiler's virus central nervous system infection.", "content": "After (IC) inoculation of the DA strain of TMEV, SJL/J mice develop chronic CNS infection with marked mononuclear cell infiltration of spinal cord leptomeninges and white matter and concomitant demyelination. In the present study the temporal course of cell-mediated and humoral immune responses to virus were measured in this infection. It was shown that chronic TMEV infection is associated with the development of immunologically specific spleen cell reactivity as judged by in vitro incorporation of 3H-TdR into DNA in response to inactivated TMEV antigen. Spleen cell reactivity is first detectable about 2 months after infection, persists for at least 1 year, and correlates with the temporal development of serum-neutralizing antibody. The late development of sensitized spleen cells is not the result of an immunosuppressive effect of this virus infection since infected mice exhibit normal spleen cell proliferative responses to T cell mitogens and produce normal antibody responses to a heterologous protein antigen, sheep red blood cells. In addition, anti-viral antibody inhibits virus-induced spleen cell reactivity. Finally, the antigen-reactive lymphocyte subpopulation within the spleen responsible for proliferation to TMEV antigen are T cells and not B cells.", "contents": "Cellular immunity in chronic Theiler's virus central nervous system infection. After (IC) inoculation of the DA strain of TMEV, SJL/J mice develop chronic CNS infection with marked mononuclear cell infiltration of spinal cord leptomeninges and white matter and concomitant demyelination. In the present study the temporal course of cell-mediated and humoral immune responses to virus were measured in this infection. It was shown that chronic TMEV infection is associated with the development of immunologically specific spleen cell reactivity as judged by in vitro incorporation of 3H-TdR into DNA in response to inactivated TMEV antigen. Spleen cell reactivity is first detectable about 2 months after infection, persists for at least 1 year, and correlates with the temporal development of serum-neutralizing antibody. The late development of sensitized spleen cells is not the result of an immunosuppressive effect of this virus infection since infected mice exhibit normal spleen cell proliferative responses to T cell mitogens and produce normal antibody responses to a heterologous protein antigen, sheep red blood cells. In addition, anti-viral antibody inhibits virus-induced spleen cell reactivity. Finally, the antigen-reactive lymphocyte subpopulation within the spleen responsible for proliferation to TMEV antigen are T cells and not B cells."} {"id": "PMID:181491", "title": "In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils.", "content": "Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced.", "contents": "In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils. Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced."} {"id": "PMID:181492", "title": "Inhibition by rheumatoid factor, anti-FC, and staphylococcal protein A of antibody-dependent cell-mediated cytolysis against Herpes simplex virus-infected cells.", "content": "Incubation of herpes simplex virus-infected human fibroblasts with the serum from a patient with herpes labialis rendered the cells susceptible to immune lysis by human mononuclear leukocytes (MNL) as well as complement. If, before the addition of MNL, the antibody-treated, infected monolayers were incubated with either IgM rheumatoid factor (RF), staphylococcal protein A (SPA), or anti-Fc gamma serum, antibody-dependent cell-mediated cytolysis (ADCC) was markedly depressed. SPA and anti-Fc caused maximal inhibition (greater than 90%), whereas RF resulted in a 72% depression. The inhibition of ADCC was dependent on both the concentration of the Fc-reacting materials incubated with the antibody-coated target cells and the concentration of antiviral antibody incubated with the virus-infected fibroblasts. Experiments indicated that the Fc-reacting materials depressed ADCC at the target cell level by covering or altering Fc sites on cell-bound antiviral antibody.", "contents": "Inhibition by rheumatoid factor, anti-FC, and staphylococcal protein A of antibody-dependent cell-mediated cytolysis against Herpes simplex virus-infected cells. Incubation of herpes simplex virus-infected human fibroblasts with the serum from a patient with herpes labialis rendered the cells susceptible to immune lysis by human mononuclear leukocytes (MNL) as well as complement. If, before the addition of MNL, the antibody-treated, infected monolayers were incubated with either IgM rheumatoid factor (RF), staphylococcal protein A (SPA), or anti-Fc gamma serum, antibody-dependent cell-mediated cytolysis (ADCC) was markedly depressed. SPA and anti-Fc caused maximal inhibition (greater than 90%), whereas RF resulted in a 72% depression. The inhibition of ADCC was dependent on both the concentration of the Fc-reacting materials incubated with the antibody-coated target cells and the concentration of antiviral antibody incubated with the virus-infected fibroblasts. Experiments indicated that the Fc-reacting materials depressed ADCC at the target cell level by covering or altering Fc sites on cell-bound antiviral antibody."} {"id": "PMID:181421", "title": "[Malignant cyto-trophoblastic tumors following the abortion of a mole. Their treatment with methotrexate alone or in conjunction with surgery].", "content": "We report six case histories of malignant tumours following abortion of moles. In three cases their surgical removal allowed us to control them by histology: two of these were destruens chorio-adenomata, one case only was a choriocarcinoma. In the three other cases the cure was obtained by the sole use of anti-mitotic drugs. This treatment was undertaken on bioclinical evidence of malignancy which is certainly not foolproof, but which is practical in use, when one appreciates how difficult it is to diagnose some of these post-mole tumours histologically. There is a place for the surgical treatment of these cases in spite of the usefulness of Methotrexate. This place varies according to the age of the patients and the resistance of the tumours to treatment with anti-mitotic drugs.", "contents": "[Malignant cyto-trophoblastic tumors following the abortion of a mole. Their treatment with methotrexate alone or in conjunction with surgery]. We report six case histories of malignant tumours following abortion of moles. In three cases their surgical removal allowed us to control them by histology: two of these were destruens chorio-adenomata, one case only was a choriocarcinoma. In the three other cases the cure was obtained by the sole use of anti-mitotic drugs. This treatment was undertaken on bioclinical evidence of malignancy which is certainly not foolproof, but which is practical in use, when one appreciates how difficult it is to diagnose some of these post-mole tumours histologically. There is a place for the surgical treatment of these cases in spite of the usefulness of Methotrexate. This place varies according to the age of the patients and the resistance of the tumours to treatment with anti-mitotic drugs."} {"id": "PMID:181494", "title": "The role of prostaglandin E, cyclic AMP, and cyclic GMP in the proliferation of guinea-pig ear skin stimulated by topical application of vitamin A acid.", "content": "Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control.", "contents": "The role of prostaglandin E, cyclic AMP, and cyclic GMP in the proliferation of guinea-pig ear skin stimulated by topical application of vitamin A acid. Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control."} {"id": "PMID:181495", "title": "Cyclic AMP-phosphodiesterase and epidermal mitosis.", "content": "The relationship between cyclic AMP-phosphodiesterase (cAMP-PDE) inhibition and inhibition of epidermal mitosis was examined for several compounds using a soluble, low Km PDE activity from hairless mouse skin and the G2 mouse ear mitosis assay. Orders of potency determined at IC50 levels (concentrations required for 50% inhibition) were SQ 20009 greater than RO 20-1724 greater than papaverine greater than bufexamac greater than indomethacin greater than theophylline greater than p-biphenylylacetic acid greater than or less than glycyrrhetinic acid for inhibition of both PDE and mitosis. The disproportionately high antimitotic potency of puromycin relative to PDE inhibition was believed to reflect effects on protein biosynthesis. Activity of the three nonsteroidal anti-inflammatory agents (bufexamac, indomethacin, and p-biphenylylacetic acid) was unrelated to their effect on prostaglandin synthesis in homogenates of hairless mouse skin. The results suggest that the epidermal antimitotic activity of the compounds tested is related to their inhibition of cAMP-PDE and provide additional support for cAMP as a regulator of the G2 stage of the epidermal cell cycle.", "contents": "Cyclic AMP-phosphodiesterase and epidermal mitosis. The relationship between cyclic AMP-phosphodiesterase (cAMP-PDE) inhibition and inhibition of epidermal mitosis was examined for several compounds using a soluble, low Km PDE activity from hairless mouse skin and the G2 mouse ear mitosis assay. Orders of potency determined at IC50 levels (concentrations required for 50% inhibition) were SQ 20009 greater than RO 20-1724 greater than papaverine greater than bufexamac greater than indomethacin greater than theophylline greater than p-biphenylylacetic acid greater than or less than glycyrrhetinic acid for inhibition of both PDE and mitosis. The disproportionately high antimitotic potency of puromycin relative to PDE inhibition was believed to reflect effects on protein biosynthesis. Activity of the three nonsteroidal anti-inflammatory agents (bufexamac, indomethacin, and p-biphenylylacetic acid) was unrelated to their effect on prostaglandin synthesis in homogenates of hairless mouse skin. The results suggest that the epidermal antimitotic activity of the compounds tested is related to their inhibition of cAMP-PDE and provide additional support for cAMP as a regulator of the G2 stage of the epidermal cell cycle."} {"id": "PMID:181496", "title": "Intranuclear tonofilaments in verruca vulgaris.", "content": "Electron microscopic examination of a verruca vulgaris has revealed the intranuclear inclusion of tonofibrils. Although many intracellular inclusions may be related directly to the virus, nonviral inclusions may also be present.", "contents": "Intranuclear tonofilaments in verruca vulgaris. Electron microscopic examination of a verruca vulgaris has revealed the intranuclear inclusion of tonofibrils. Although many intracellular inclusions may be related directly to the virus, nonviral inclusions may also be present."} {"id": "PMID:181497", "title": "Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines. II. Kinetics of neutralizing antibody responses in donors and adoptively immunized recipients.", "content": "Lymphoid cell responses to immunization with various formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccines were monitored in mice by assessment of the development of both the neutralizing antibody response in sera of spleen cell donors and the adoptive neutralizing antibody response induced by spleen cell transfer in recipients. Donors immunized intraperitoneally with formalin-inactivated VEE vaccine (a single dose or a dose on three consecutive days) developed early serum neutralizing antibody responses (larger than or equal to 1:88-1:100) by seven days after immunization. Recipients of spleen cells from such mice were, however, incapable of eliciting a neutralizing antibody response (less than or equal to 1:10). Only spleen cells from donors immunized with inactivated VEE vaccine plus adjuvants (particularly complete Freund's adjuvant and Bordetella pertussis) were consistently capable of producing early, high-titer serum neutralizing antibody responses in adoptively immunized recipients (larger than or equal to 1:50-1:120 on day 4). The magnitude of neutralizing antibody responses of donors to inactivated VEE vaccines did not serve as a useful indicator of whether spleen cells from such mice could adoptively induce antibody responses in recipients. Finally, treatment of immune spleen cells with rabbit antiserum to mouse thymocytes, but not with rabbit antiserum to mouse gamma-globulin or normal rabbit serum, abolished the capacity of such cells to transfer an antibody response adoptively.", "contents": "Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines. II. Kinetics of neutralizing antibody responses in donors and adoptively immunized recipients. Lymphoid cell responses to immunization with various formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccines were monitored in mice by assessment of the development of both the neutralizing antibody response in sera of spleen cell donors and the adoptive neutralizing antibody response induced by spleen cell transfer in recipients. Donors immunized intraperitoneally with formalin-inactivated VEE vaccine (a single dose or a dose on three consecutive days) developed early serum neutralizing antibody responses (larger than or equal to 1:88-1:100) by seven days after immunization. Recipients of spleen cells from such mice were, however, incapable of eliciting a neutralizing antibody response (less than or equal to 1:10). Only spleen cells from donors immunized with inactivated VEE vaccine plus adjuvants (particularly complete Freund's adjuvant and Bordetella pertussis) were consistently capable of producing early, high-titer serum neutralizing antibody responses in adoptively immunized recipients (larger than or equal to 1:50-1:120 on day 4). The magnitude of neutralizing antibody responses of donors to inactivated VEE vaccines did not serve as a useful indicator of whether spleen cells from such mice could adoptively induce antibody responses in recipients. Finally, treatment of immune spleen cells with rabbit antiserum to mouse thymocytes, but not with rabbit antiserum to mouse gamma-globulin or normal rabbit serum, abolished the capacity of such cells to transfer an antibody response adoptively."} {"id": "PMID:181498", "title": "Effect of human immune serum globulin on infectivity of hepatitis A virus.", "content": "A standard preparation of immune serum globulin containing a titer of immune adherence hemagglutination hepatitis A antibody of 1:3,200 neutralized the infectivity of MS-1 serum. An inoculation of MS-1 serum was followed by the following evidence of hepatitis A infection in eight of 14 seronegative recipients: (1) abnormal values for serum aspartate aminotransferase after an incubation period of 29-42 days, and (2) no detectable immune adherence hemagglutination hepatitis A antibody (less than 1:5) before exposure, and an eightfold or greater increase in antibody titer during convalescence. In contrast, inoculation of the mixture of MS-1 serum and immune serum globulin was followed by (1) normal values for aspartate aminotransferase in all eight seronegative recipients, and (2) evidence of an antibody response (indicating subclinical infection) in two of the eight. Under the conditions of this study, the use of the preparation of immune serum globulin described prevented or modified hepatitis A infection.", "contents": "Effect of human immune serum globulin on infectivity of hepatitis A virus. A standard preparation of immune serum globulin containing a titer of immune adherence hemagglutination hepatitis A antibody of 1:3,200 neutralized the infectivity of MS-1 serum. An inoculation of MS-1 serum was followed by the following evidence of hepatitis A infection in eight of 14 seronegative recipients: (1) abnormal values for serum aspartate aminotransferase after an incubation period of 29-42 days, and (2) no detectable immune adherence hemagglutination hepatitis A antibody (less than 1:5) before exposure, and an eightfold or greater increase in antibody titer during convalescence. In contrast, inoculation of the mixture of MS-1 serum and immune serum globulin was followed by (1) normal values for aspartate aminotransferase in all eight seronegative recipients, and (2) evidence of an antibody response (indicating subclinical infection) in two of the eight. Under the conditions of this study, the use of the preparation of immune serum globulin described prevented or modified hepatitis A infection."} {"id": "PMID:181499", "title": "Microbiologic assays and neurological toxicity during use of adenine arabinoside in humans.", "content": "Patients with herpesvirus infections were given intravenous injections of 10-20 mg of adenine arabinoside (ara-A)/kg per day. When given the higher dosage, some patients with chronic hematologic conditions showed mild to moderate additional depressions in the level of hemoglobin. The number of neutrophils and platelets did not decrease, even when numbers were low at the onset of treatment with ara-A. Two patients with Hodgkin's disease who received 20 mg of ara-A/kg per day developed a transient motor aphasia resembling akinetic mutism. With the regimens of ara-A used and challenge inocula of approximately 50 plaque-forming units of virus, the minimal inhibitory concentrations of ara-A and hypoxanthine arabinoside for herpesviruses are usually not achieved in serum but may be attained in body fluids (urine and vesicular fluid). Antiviral activity in vesicular fluids is likely to involve a combination of ara-A, hypoxanthine arabinoside, and interferon.", "contents": "Microbiologic assays and neurological toxicity during use of adenine arabinoside in humans. Patients with herpesvirus infections were given intravenous injections of 10-20 mg of adenine arabinoside (ara-A)/kg per day. When given the higher dosage, some patients with chronic hematologic conditions showed mild to moderate additional depressions in the level of hemoglobin. The number of neutrophils and platelets did not decrease, even when numbers were low at the onset of treatment with ara-A. Two patients with Hodgkin's disease who received 20 mg of ara-A/kg per day developed a transient motor aphasia resembling akinetic mutism. With the regimens of ara-A used and challenge inocula of approximately 50 plaque-forming units of virus, the minimal inhibitory concentrations of ara-A and hypoxanthine arabinoside for herpesviruses are usually not achieved in serum but may be attained in body fluids (urine and vesicular fluid). Antiviral activity in vesicular fluids is likely to involve a combination of ara-A, hypoxanthine arabinoside, and interferon."} {"id": "PMID:181500", "title": "Hepatitis A antigen particles in liver, bile, and stool of chimpanzees.", "content": "Virus-like hepatitis A antigen (HA Ag) particles, presumably hepatitis A virus, were isolated from the liver, bile, and stool of three chimpanzees that had been infected with stool filtrates containing HA Ag particles. Specimens of serum, stool, liver biopsy material, and bile were obtained at selected intervals during the experiment. The animals developed mild hepatitis 19-21 days after inoculation, and antibody to HA Ag appeared de novo in their convalescent-phase serum. During acute illness, virus-like particles similar to the HA Ag particle were seen in liver cell cytoplasm by electron microscopy. HA Ag particles were detected by immune electron microscopy and a new radioimmunoassay in isopycnically banded samples of liver, bile, and stool. HA Ag particles were found at densities of 1.29-1.39 g/cm3, but the major peak density for antigen particles in samples of liver, bile, and stool was approximately 1.34 g/cm3. The fact that HA Ag particles can be recovered from chimpanzee liver, bile, and stool makes these potentially important sources of infectious and antigenic materials.", "contents": "Hepatitis A antigen particles in liver, bile, and stool of chimpanzees. Virus-like hepatitis A antigen (HA Ag) particles, presumably hepatitis A virus, were isolated from the liver, bile, and stool of three chimpanzees that had been infected with stool filtrates containing HA Ag particles. Specimens of serum, stool, liver biopsy material, and bile were obtained at selected intervals during the experiment. The animals developed mild hepatitis 19-21 days after inoculation, and antibody to HA Ag appeared de novo in their convalescent-phase serum. During acute illness, virus-like particles similar to the HA Ag particle were seen in liver cell cytoplasm by electron microscopy. HA Ag particles were detected by immune electron microscopy and a new radioimmunoassay in isopycnically banded samples of liver, bile, and stool. HA Ag particles were found at densities of 1.29-1.39 g/cm3, but the major peak density for antigen particles in samples of liver, bile, and stool was approximately 1.34 g/cm3. The fact that HA Ag particles can be recovered from chimpanzee liver, bile, and stool makes these potentially important sources of infectious and antigenic materials."} {"id": "PMID:181502", "title": "The transport of alpha-tocopherol and beta-carotene in human blood.", "content": "The concentrations and distributions of major lipids (cholesterol, phospholipid, and triglyceride), tocopherol and carotenoids were determined in the plasma lipoprotein fractions (VLDL, LDL, and HDL) of (1) normal human subjects, (2) patients with hyperlipoproteinemia, and (3) patients with erythropoietic protoporphyria treated with oral beta-carotene and/or alpha-tocopherol. The distribution of tocopherol (in percent) was most closely correlated with the distribution of total lipids in the individual lipoproteins, while the major portion of beta-carotene was present in the low density lipoproteins, irrespective of the lipid distribution in the lipoproteins (except for one subject with hyperchylomicronemia). The alpha-tocopherol and beta-carotene concentrations of plasma and RBC in patients treated with tocopherol and carotene were determined periodically for a one-year period. Plasma and RBC tocopherol concentrations showed a rapid, parallel increase in response to tocopherol supplementation. In contrast, the plasma and RBC carotene concentrations showed a much slower and nonparallel increase in response to carotene administration. When carotene supplementation was stopped, the elevated carotene levels in both plasma and RBC persisted for several months; the elevated plasma carotene level persisted longer than the raised RBC carotene levels. These results suggest that alpha-tocopherol and beta-carotene are transported differently in the circulation and that the tissue storage and mobilization of these compounds are different.", "contents": "The transport of alpha-tocopherol and beta-carotene in human blood. The concentrations and distributions of major lipids (cholesterol, phospholipid, and triglyceride), tocopherol and carotenoids were determined in the plasma lipoprotein fractions (VLDL, LDL, and HDL) of (1) normal human subjects, (2) patients with hyperlipoproteinemia, and (3) patients with erythropoietic protoporphyria treated with oral beta-carotene and/or alpha-tocopherol. The distribution of tocopherol (in percent) was most closely correlated with the distribution of total lipids in the individual lipoproteins, while the major portion of beta-carotene was present in the low density lipoproteins, irrespective of the lipid distribution in the lipoproteins (except for one subject with hyperchylomicronemia). The alpha-tocopherol and beta-carotene concentrations of plasma and RBC in patients treated with tocopherol and carotene were determined periodically for a one-year period. Plasma and RBC tocopherol concentrations showed a rapid, parallel increase in response to tocopherol supplementation. In contrast, the plasma and RBC carotene concentrations showed a much slower and nonparallel increase in response to carotene administration. When carotene supplementation was stopped, the elevated carotene levels in both plasma and RBC persisted for several months; the elevated plasma carotene level persisted longer than the raised RBC carotene levels. These results suggest that alpha-tocopherol and beta-carotene are transported differently in the circulation and that the tissue storage and mobilization of these compounds are different."} {"id": "PMID:181503", "title": "Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate.", "content": "The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established.", "contents": "Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate. The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established."} {"id": "PMID:181504", "title": "An improved two dimensional thin-layer chromatography system for the separation of phosphatidylglycerol and its derivatives.", "content": "A two dimensional thin-layer chromatography system has been devised for the improved separations of phosphatidylglycerol and its derivaties, cardiolipin and bis/monoacylglyceryl)phosphate, from the other phospholipid components of tissue total lipid extracts. The system employs silica gel G plates prepared with 0.4 M boric acid. Linear recovery of added phosphatidylglycerol was found, and phosphatidylglycerol did not cochromatograph with N, N-dimethylphosphatidylethanolamine in this system. The phospholipid class composition of various rat tissues and a Morris 7777 hepatoma has been determined and compared with values from the literature.", "contents": "An improved two dimensional thin-layer chromatography system for the separation of phosphatidylglycerol and its derivatives. A two dimensional thin-layer chromatography system has been devised for the improved separations of phosphatidylglycerol and its derivaties, cardiolipin and bis/monoacylglyceryl)phosphate, from the other phospholipid components of tissue total lipid extracts. The system employs silica gel G plates prepared with 0.4 M boric acid. Linear recovery of added phosphatidylglycerol was found, and phosphatidylglycerol did not cochromatograph with N, N-dimethylphosphatidylethanolamine in this system. The phospholipid class composition of various rat tissues and a Morris 7777 hepatoma has been determined and compared with values from the literature."} {"id": "PMID:181514", "title": "Blood corticosteroids in Australian marsupial and placental mammals and one monotreme.", "content": "Peripheral blood corticosteroid levels were determined in nine species of Australian marsupial (Eastern grey kangaroo, black-tailed, Bennett's and pademelon wallabies, quokka, wombat, koala and Western native and tiger cats), one species of monotreme (echidna) and one placental Australian mammal (dingo). Animals were obtained or bled with minimal disturbance and came from areas considered to have adequate sodium content of the vegetation. Aldosterone, corticosterone, cortisol, 11-deoxycorticosterone and 11-deoxycortisol were measured and levels found to be similar to five introduced eutherian species (sheep, cow, dog, fox and man) with the exception of the koala and the wombat. Cortisol was the predominant corticosteroid, except in the koala, which produced corticosterone in relatively the greatest quantity, and the wombat which produced more 11-deoxycortisol. Steroid levels were generally low in the wombat. ACTH administered to the koala changed its pattern of corticosteroid secretion from predominantly corticosterone to cortisol. In the dingo, administration of ACTH caused rises in corticosteroid levels similar to those seen in most other eutherian mammals.", "contents": "Blood corticosteroids in Australian marsupial and placental mammals and one monotreme. Peripheral blood corticosteroid levels were determined in nine species of Australian marsupial (Eastern grey kangaroo, black-tailed, Bennett's and pademelon wallabies, quokka, wombat, koala and Western native and tiger cats), one species of monotreme (echidna) and one placental Australian mammal (dingo). Animals were obtained or bled with minimal disturbance and came from areas considered to have adequate sodium content of the vegetation. Aldosterone, corticosterone, cortisol, 11-deoxycorticosterone and 11-deoxycortisol were measured and levels found to be similar to five introduced eutherian species (sheep, cow, dog, fox and man) with the exception of the koala and the wombat. Cortisol was the predominant corticosteroid, except in the koala, which produced corticosterone in relatively the greatest quantity, and the wombat which produced more 11-deoxycortisol. Steroid levels were generally low in the wombat. ACTH administered to the koala changed its pattern of corticosteroid secretion from predominantly corticosterone to cortisol. In the dingo, administration of ACTH caused rises in corticosteroid levels similar to those seen in most other eutherian mammals."} {"id": "PMID:181515", "title": "Steroidogenic pathways and trophic response to adrenocorticotrophin of cultured adrenocortical cells in different states of differentiation.", "content": "Adrenocortical cells obtained from adult rats were propagated in monolayer culture. Depending on culture conditions, they grew either as lipid-containing epithelial-like cells with a high level of steroid production, or as fibroblast-like cells with a low level of steroid production. The major fluorogenic steroid secreted by both morphologic forms of adrenal cortical cell was corticosterone as determined by chromatography and acid fluorometry. Basal fluorogenic steroid production per 10(6) cells over 24 h was: epithelial-like cells, 5.0-mug; fibroblast-like cells, 0-014 mug. Stimulation with ACTH for 5 days increased fluorogenic steroid production and induced morphologic changes in both adrenal cell forms. ACTH stimulation of fluorogenic steroid production by both cell forms reached a maximum after 3 days, then dropped to a refractory state after 5 days. With maximal ACTH stimulation, production increased 25-fold in fibroblast-like cells and five-fold in epithelial-like cells. The latter rate of corticosterone production is similar, per cell, to ACTH-stimulated adrenal glands in vivo. Progressive morphologic changes were observed with ACTH stimulation: epithelial-like cells retracted from the substratum and lost lipid inclusions; fibroblast-like cells became more epithelial-like. Both adrenal cell types formed intermediates from [4-(14)C] pregnenolone including pregn-5-ene-3 phi, 20 alpha-diol and 20 alpha-hydroxy-pregn-4-en-3-one. Control cultures of muscle fascia fibroblasts did not produce corticosterone or intermediates from [4-(14)C[ pregnenolone and did not respond to ACTH functionally or morphologically.", "contents": "Steroidogenic pathways and trophic response to adrenocorticotrophin of cultured adrenocortical cells in different states of differentiation. Adrenocortical cells obtained from adult rats were propagated in monolayer culture. Depending on culture conditions, they grew either as lipid-containing epithelial-like cells with a high level of steroid production, or as fibroblast-like cells with a low level of steroid production. The major fluorogenic steroid secreted by both morphologic forms of adrenal cortical cell was corticosterone as determined by chromatography and acid fluorometry. Basal fluorogenic steroid production per 10(6) cells over 24 h was: epithelial-like cells, 5.0-mug; fibroblast-like cells, 0-014 mug. Stimulation with ACTH for 5 days increased fluorogenic steroid production and induced morphologic changes in both adrenal cell forms. ACTH stimulation of fluorogenic steroid production by both cell forms reached a maximum after 3 days, then dropped to a refractory state after 5 days. With maximal ACTH stimulation, production increased 25-fold in fibroblast-like cells and five-fold in epithelial-like cells. The latter rate of corticosterone production is similar, per cell, to ACTH-stimulated adrenal glands in vivo. Progressive morphologic changes were observed with ACTH stimulation: epithelial-like cells retracted from the substratum and lost lipid inclusions; fibroblast-like cells became more epithelial-like. Both adrenal cell types formed intermediates from [4-(14)C] pregnenolone including pregn-5-ene-3 phi, 20 alpha-diol and 20 alpha-hydroxy-pregn-4-en-3-one. Control cultures of muscle fascia fibroblasts did not produce corticosterone or intermediates from [4-(14)C[ pregnenolone and did not respond to ACTH functionally or morphologically."} {"id": "PMID:181516", "title": "Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney.", "content": "Both guanosine 5'-triphosphate (GTP) AND 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase (EC4.6.1.1) in chick kidney plasma membranes. Half-maximal stimulation occurred at 3-1 X 10(-6)M for both agents. The maximum increases in adenylate cyclase activity produced by GTP and Gpp(NH)p were respectively 130 and 720% over basal activity. At the end of a 12 min incubation period GTP concentration was 85% of that originally added in the presence of an ATP-regenerating system but less than 20% in its absence. GTP and guanosine 5'-diphosphate inhibited the activation of adenylate cyclase by Gpp(NH)p, suggesting that they all acted at a common site. Gpp(NH)p facilitated the stimulation of adenylate cyclase activity by bovine parathyroid hormone (BPTH) and by the synthetic amino terminal fragment BPTH (1-34), decreasing the concentrations required for half-maximal enzyme activation by a factor of approximately eight in both cases. This property was not shared by the native nucleotide GTP. Gpp(NH)p rendered active (at certain concentrations) a synthetic parathyroid hormone peptide fragment, BPTH (2-34), which was incapable of Activating adenylate cyclase in the absence of the nucleotide analogue. This suggested that the GTP analogue, in addition to a direct effect upon adenylate cyclase activity, was capable of influencing hormone interaction with the enzyme complex.", "contents": "Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney. Both guanosine 5'-triphosphate (GTP) AND 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase (EC4.6.1.1) in chick kidney plasma membranes. Half-maximal stimulation occurred at 3-1 X 10(-6)M for both agents. The maximum increases in adenylate cyclase activity produced by GTP and Gpp(NH)p were respectively 130 and 720% over basal activity. At the end of a 12 min incubation period GTP concentration was 85% of that originally added in the presence of an ATP-regenerating system but less than 20% in its absence. GTP and guanosine 5'-diphosphate inhibited the activation of adenylate cyclase by Gpp(NH)p, suggesting that they all acted at a common site. Gpp(NH)p facilitated the stimulation of adenylate cyclase activity by bovine parathyroid hormone (BPTH) and by the synthetic amino terminal fragment BPTH (1-34), decreasing the concentrations required for half-maximal enzyme activation by a factor of approximately eight in both cases. This property was not shared by the native nucleotide GTP. Gpp(NH)p rendered active (at certain concentrations) a synthetic parathyroid hormone peptide fragment, BPTH (2-34), which was incapable of Activating adenylate cyclase in the absence of the nucleotide analogue. This suggested that the GTP analogue, in addition to a direct effect upon adenylate cyclase activity, was capable of influencing hormone interaction with the enzyme complex."} {"id": "PMID:181523", "title": "Isoenzyme transitions of creatine phosphokinase, aldolase and phosphoglycerate mutase in differentiating mouse cells.", "content": "Extracts of embryonic mouse tissues (skeletal, cardiac and smooth muscle, and brain) were analysed by Cellogel electrophoresis for their isoenzymic distributions of three enzymes, creatine phosphokinase, aldolase and phosphoglycerate mutase. Embryonic tissues from the 12th day to the end of gestation were examined for isoenzyme transitions, and it was found that the adult forms of these enzymes appeared during gestation. Extracts from cloned teratocarcinoma cells were similarly examined in order to determine their degree of bio-chemical differentiation. Undifferentiated embryonal carcinoma cells contained only the early embryonic forms of all three enzymes, while differentiated cells formed in vivo, and in some cases in vitro, started to express the adult types of creatine phosphokinase and aldolase. Thus, biochemical parallels have been demonstrated between developing embryonic tissues and teratocarcinoma cells differentiating in vitro.", "contents": "Isoenzyme transitions of creatine phosphokinase, aldolase and phosphoglycerate mutase in differentiating mouse cells. Extracts of embryonic mouse tissues (skeletal, cardiac and smooth muscle, and brain) were analysed by Cellogel electrophoresis for their isoenzymic distributions of three enzymes, creatine phosphokinase, aldolase and phosphoglycerate mutase. Embryonic tissues from the 12th day to the end of gestation were examined for isoenzyme transitions, and it was found that the adult forms of these enzymes appeared during gestation. Extracts from cloned teratocarcinoma cells were similarly examined in order to determine their degree of bio-chemical differentiation. Undifferentiated embryonal carcinoma cells contained only the early embryonic forms of all three enzymes, while differentiated cells formed in vivo, and in some cases in vitro, started to express the adult types of creatine phosphokinase and aldolase. Thus, biochemical parallels have been demonstrated between developing embryonic tissues and teratocarcinoma cells differentiating in vitro."} {"id": "PMID:181524", "title": "Quantitation of the spatial distribution of 'prespore vacuoles' in pseudoplasmodia of Dictyostelium discoideum.", "content": "The axial distribution of an organelle, the prespore vacuole (PV), previously reported absent from the prestalk region, was determined in pseudoplasmodia of varying sizes, under differing conditions of photostimulation of migration. The distribution of these organelles, determined quantitatively by electron microscopy of sections from known axial locations, was found to have a spatial pattern which varied with pseudoplasmodial size. The total complement of these organelles appeared constant for any size of pseudoplasmodium under similar conditions of illumination. Increased illumination decreased the total number of the organelles. The spatial distribution of PV varies with total cell number, and the size of the region with no PV bears no relationship to the proportion of the cell mass which would form stalk cells. Similarly, the number of cells containing PV bears no fixed relationship to the number of cells which will form spores. On these grounds, the reported role of PV, that of directing or reflecting spore differentiation, appears unlikely.", "contents": "Quantitation of the spatial distribution of 'prespore vacuoles' in pseudoplasmodia of Dictyostelium discoideum. The axial distribution of an organelle, the prespore vacuole (PV), previously reported absent from the prestalk region, was determined in pseudoplasmodia of varying sizes, under differing conditions of photostimulation of migration. The distribution of these organelles, determined quantitatively by electron microscopy of sections from known axial locations, was found to have a spatial pattern which varied with pseudoplasmodial size. The total complement of these organelles appeared constant for any size of pseudoplasmodium under similar conditions of illumination. Increased illumination decreased the total number of the organelles. The spatial distribution of PV varies with total cell number, and the size of the region with no PV bears no relationship to the proportion of the cell mass which would form stalk cells. Similarly, the number of cells containing PV bears no fixed relationship to the number of cells which will form spores. On these grounds, the reported role of PV, that of directing or reflecting spore differentiation, appears unlikely."} {"id": "PMID:181525", "title": "Biochemical correlates of adaptation processes in isolated frog photoreceptor membranes.", "content": "Frog rod outer segments isolated in suspension can maintain much of their in vivo activity. This observation provides us with a simpler system than the intact retina for correlating biochemical and physiological changes. The relevant physiological process, a decrease of sodium permeability by illumination, is assayed as light suppression of outer segment swelling in a modified Ringer's solution. We report here that this decrease is observed over approximately 4 log units of input light intensity and varies with the logarithm of intensity at light levels which bleach between 5.102 and 5.104 rhodopsin molecules/outer segment-second. In this illumination range responsiveness to light decreases as intensity increases. This sensitivity control system may be linked to light-activated rhodopsin phosphorylation, for inhibitors of this reaction increase light sensitivity. The presence of a second system, which controls the maximum amplitude of in vitro response to light, is revealed in experiments with cyclic nucleotide phosphodiesterase inhibitors. Papaverine addition raises intracellular cyclic GMP (guanosine monophosphate) levels and increases the magnitude of the dark permeability, but does not have a large influence on the amount of illumination required for suppression of this permeability. The data suggest that sensitivity and amplitude, as they are expressed in this in vitro system, are regulated by pharmacologically distinct pathways which use two different light-sensitive enzyme systems.", "contents": "Biochemical correlates of adaptation processes in isolated frog photoreceptor membranes. Frog rod outer segments isolated in suspension can maintain much of their in vivo activity. This observation provides us with a simpler system than the intact retina for correlating biochemical and physiological changes. The relevant physiological process, a decrease of sodium permeability by illumination, is assayed as light suppression of outer segment swelling in a modified Ringer's solution. We report here that this decrease is observed over approximately 4 log units of input light intensity and varies with the logarithm of intensity at light levels which bleach between 5.102 and 5.104 rhodopsin molecules/outer segment-second. In this illumination range responsiveness to light decreases as intensity increases. This sensitivity control system may be linked to light-activated rhodopsin phosphorylation, for inhibitors of this reaction increase light sensitivity. The presence of a second system, which controls the maximum amplitude of in vitro response to light, is revealed in experiments with cyclic nucleotide phosphodiesterase inhibitors. Papaverine addition raises intracellular cyclic GMP (guanosine monophosphate) levels and increases the magnitude of the dark permeability, but does not have a large influence on the amount of illumination required for suppression of this permeability. The data suggest that sensitivity and amplitude, as they are expressed in this in vitro system, are regulated by pharmacologically distinct pathways which use two different light-sensitive enzyme systems."} {"id": "PMID:181526", "title": "Growth on D-arabitol of a mutant strain of Escherichia coli K12 using a novel dehydrogenase and enzymes related to L-1,2-propanediol and D-xylose metabolism.", "content": "Escherichia coli K12 cannot grow on D-arabitol, L-arabitol, ribitol or xylitol (Reiner, 1975). Using a mutant of E. coli K12 (strain 3; Sridhara et al., 1969) that can grow on L-1,2-propanediol, a second-stage mutant was isolated which can utilize D-arabitol as sole source of carbon and energy for growth. D-Arabitol is probably transported into the bacteria by the same system as that used for the transport of L-1,2-propanediol. The second-stage mutant constitutively synthesizes a new dehydrogenase, which is not present in the parent strain 3. This enzyme, whose native substrate may be D-galactose, apparently dehydrogenates D-arabitol to D-xylulose, and its structural gene is located at 68.5 +/- 1 min on the E. coli genetic map. D-Xylulose is subsequently catabolized by the enzymes of the D-xylose metabolic pathway.", "contents": "Growth on D-arabitol of a mutant strain of Escherichia coli K12 using a novel dehydrogenase and enzymes related to L-1,2-propanediol and D-xylose metabolism. Escherichia coli K12 cannot grow on D-arabitol, L-arabitol, ribitol or xylitol (Reiner, 1975). Using a mutant of E. coli K12 (strain 3; Sridhara et al., 1969) that can grow on L-1,2-propanediol, a second-stage mutant was isolated which can utilize D-arabitol as sole source of carbon and energy for growth. D-Arabitol is probably transported into the bacteria by the same system as that used for the transport of L-1,2-propanediol. The second-stage mutant constitutively synthesizes a new dehydrogenase, which is not present in the parent strain 3. This enzyme, whose native substrate may be D-galactose, apparently dehydrogenates D-arabitol to D-xylulose, and its structural gene is located at 68.5 +/- 1 min on the E. coli genetic map. D-Xylulose is subsequently catabolized by the enzymes of the D-xylose metabolic pathway."} {"id": "PMID:181527", "title": "A comparative analysis of the ultrastructure of hydrocarbon-oxidizing micro-organisms.", "content": "The ultrastructure of a variety of micro-organisms was compared after growth on hydrocarbon and non-hydrocarbon substrates. Hydrocarbon-grown organisms were characterized by the presence of intracellular electron-transparent inclusions which in many cases appeared membrane-bound. With one exception, non-hydrocarbon-grown organisms did not contain electron-transparent inclusions. Insignificant amounts of poly-beta-hydroxybutyric acid were produced by the hydrocarbon-grown micro-organisms. After growth on hydrocarbons, all the microorganisms had accumulated varying amounts of the respective unmodified hydrocarbon growth substrate.", "contents": "A comparative analysis of the ultrastructure of hydrocarbon-oxidizing micro-organisms. The ultrastructure of a variety of micro-organisms was compared after growth on hydrocarbon and non-hydrocarbon substrates. Hydrocarbon-grown organisms were characterized by the presence of intracellular electron-transparent inclusions which in many cases appeared membrane-bound. With one exception, non-hydrocarbon-grown organisms did not contain electron-transparent inclusions. Insignificant amounts of poly-beta-hydroxybutyric acid were produced by the hydrocarbon-grown micro-organisms. After growth on hydrocarbons, all the microorganisms had accumulated varying amounts of the respective unmodified hydrocarbon growth substrate."} {"id": "PMID:181528", "title": "Acid phosphatase activity in the wild-type and B-mutant hyphae of Schizophyllum commune.", "content": "In the wild-type and B-mutant hyphae of Schizophyllum commune, acid phosphatase activity was found in association with vacuoles, lipid bodies, and endoplasmic reticulum. Small granules containing acid phosphatase also occurred in mitochondria and along the nuclear envelope. Both ultrastructural and biochemical studies indicated greater acid phosphatase activity in the B-mutant than in the wild-type hyphae, which suggests that the mutation in the B incompatibility factor increases the production of the acid phosphatase in the mutant hyphae.", "contents": "Acid phosphatase activity in the wild-type and B-mutant hyphae of Schizophyllum commune. In the wild-type and B-mutant hyphae of Schizophyllum commune, acid phosphatase activity was found in association with vacuoles, lipid bodies, and endoplasmic reticulum. Small granules containing acid phosphatase also occurred in mitochondria and along the nuclear envelope. Both ultrastructural and biochemical studies indicated greater acid phosphatase activity in the B-mutant than in the wild-type hyphae, which suggests that the mutation in the B incompatibility factor increases the production of the acid phosphatase in the mutant hyphae."} {"id": "PMID:181530", "title": "Induction of cellular DNA synthesis and increased mitotic activity in syrian hamster embryo cells abortively infected with human cytomegalovirus.", "content": "The effect of human cytomegalovirus (CMV) on cell DNA synthesis and mitotic activity in hamster embryo fibroblasts was examined. The results indicated that CMV infected cells had increased rates of cell DNA replication and mitotic activity. Detection of the effect of CMV on these two parameters necessitated arrest of cells prior to infection with low serum concentrations. This lowered the background levels of DNA synthesis and cell division so that the effect of virus infection could be detected. The data indicate that cells arrested prior to infection demonstrate increased susceptibility to virus infection. It was also observed that the effect of CMV on both DNA replication and mitotic activity could be enhanced by irradiation with ultraviolet light of the virus prior to infection.", "contents": "Induction of cellular DNA synthesis and increased mitotic activity in syrian hamster embryo cells abortively infected with human cytomegalovirus. The effect of human cytomegalovirus (CMV) on cell DNA synthesis and mitotic activity in hamster embryo fibroblasts was examined. The results indicated that CMV infected cells had increased rates of cell DNA replication and mitotic activity. Detection of the effect of CMV on these two parameters necessitated arrest of cells prior to infection with low serum concentrations. This lowered the background levels of DNA synthesis and cell division so that the effect of virus infection could be detected. The data indicate that cells arrested prior to infection demonstrate increased susceptibility to virus infection. It was also observed that the effect of CMV on both DNA replication and mitotic activity could be enhanced by irradiation with ultraviolet light of the virus prior to infection."} {"id": "PMID:181531", "title": "Temperature-sensitive mutants of herpes simplex virus type 2: a provisional linkage map based on recombination analysis.", "content": "Thirteen ts mutants of type 2 herpes simplex virus were backcrossed to a syncytial but not temperature-sensitive mutant of wild-type virus. This was an attempt to introduce a third marker, syncytial plaque morphology or syn, into at least some of the ts mutants. Three ts mutants carrying the syn marker were obtained but only one, ts 9, was satisfactory for genetic experiments. Three-factor crosses were carried out between ts 9 syn and the mutants which determined the order of eleven ts mutations relative to both the ts 9 mutation and the syn mutation. A provisional linkage map based both on the order derived from the three-factor crosses and on map distances from recombination frequencies has been prepared: it contains nine ts mutations and the syn mutation.", "contents": "Temperature-sensitive mutants of herpes simplex virus type 2: a provisional linkage map based on recombination analysis. Thirteen ts mutants of type 2 herpes simplex virus were backcrossed to a syncytial but not temperature-sensitive mutant of wild-type virus. This was an attempt to introduce a third marker, syncytial plaque morphology or syn, into at least some of the ts mutants. Three ts mutants carrying the syn marker were obtained but only one, ts 9, was satisfactory for genetic experiments. Three-factor crosses were carried out between ts 9 syn and the mutants which determined the order of eleven ts mutations relative to both the ts 9 mutation and the syn mutation. A provisional linkage map based both on the order derived from the three-factor crosses and on map distances from recombination frequencies has been prepared: it contains nine ts mutations and the syn mutation."} {"id": "PMID:181532", "title": "Temperature-sensitive mutants of herpes simplex virus type 2: description of three new complementation groups and studies on the inhibition of host cell DNA synthesis.", "content": "Three new complementation groups of type 2 herpes simplex virus are described bringing the total number of complementation groups characterized to 13. Of the three new groups, ts 11 fails to make virus DNA at non-permissive temperature (38 degrees C) whereas ts 12 and ts 13 synthesize only very small amounts of virus or cellular DNA at 38 degrees C. ts 11, like ts 9 (Halliburton & Timbury, 1973) fails to switch off host cell DNA synthesis at 38 degrees C. That this is a failure to switch off cell DNA rather than a stimulation of cell DNA synthesis was confirmed in experiments using resting cells. Both the inability to make virus DNA and the inability to switch off cell DNA are reversed in temperature shift-down experiments with cells infected with ts 9 or ts 11. In temperature shift-up experiments, cellular DNA synthesis is inhibited after the shift but virus DNA is only made in very small amounts, probably due to the continuing functioning of a protein made at permissive temperature (31 degrees C) before the shift but which cannot be made at 38 degrees C. The shift-down experiments and the fact that ts 9 and ts 11 complement one another, suggest that the switch-off of host cell DNA synthesis may involve more than one virus specified function. U.v. irradiated virus fails to switch off host cell DNA synthesis.", "contents": "Temperature-sensitive mutants of herpes simplex virus type 2: description of three new complementation groups and studies on the inhibition of host cell DNA synthesis. Three new complementation groups of type 2 herpes simplex virus are described bringing the total number of complementation groups characterized to 13. Of the three new groups, ts 11 fails to make virus DNA at non-permissive temperature (38 degrees C) whereas ts 12 and ts 13 synthesize only very small amounts of virus or cellular DNA at 38 degrees C. ts 11, like ts 9 (Halliburton & Timbury, 1973) fails to switch off host cell DNA synthesis at 38 degrees C. That this is a failure to switch off cell DNA rather than a stimulation of cell DNA synthesis was confirmed in experiments using resting cells. Both the inability to make virus DNA and the inability to switch off cell DNA are reversed in temperature shift-down experiments with cells infected with ts 9 or ts 11. In temperature shift-up experiments, cellular DNA synthesis is inhibited after the shift but virus DNA is only made in very small amounts, probably due to the continuing functioning of a protein made at permissive temperature (31 degrees C) before the shift but which cannot be made at 38 degrees C. The shift-down experiments and the fact that ts 9 and ts 11 complement one another, suggest that the switch-off of host cell DNA synthesis may involve more than one virus specified function. U.v. irradiated virus fails to switch off host cell DNA synthesis."} {"id": "PMID:181533", "title": "Interaction of mouse peritoneal macrophages with fixed rabies virus in vivo and in vitro.", "content": "The resistance of mice to intraperitoneal and intramuscular infection with fixed rabies virus increases with age. Treatment of mature animals with either silica, indian ink or antimacrophage serum, which are cytotoxic for macrophages, reduced their resistance to intraperitoneal, but not to intramuscular or intracerebral infection. Transfer of peritoneal macrophages from adults to syngeneic suckling mice delayed but did not prevent mortality from intraperitoneal infection: transfer of peritoneal macrophages to intramuscular sites of infection did not protect adult mice. Rabies virus was phagocytosed by peritoneal macrophages in culture but neither replicated nor induced interferon. Evidence of active intracellular destruction of virus was obscured by thermal inactivation at 37 degrees C. Less inactivation occurred at 33 degrees C. Infected macrophages from suckling mice, but not those from adult mice, spread infection to susceptible cells.", "contents": "Interaction of mouse peritoneal macrophages with fixed rabies virus in vivo and in vitro. The resistance of mice to intraperitoneal and intramuscular infection with fixed rabies virus increases with age. Treatment of mature animals with either silica, indian ink or antimacrophage serum, which are cytotoxic for macrophages, reduced their resistance to intraperitoneal, but not to intramuscular or intracerebral infection. Transfer of peritoneal macrophages from adults to syngeneic suckling mice delayed but did not prevent mortality from intraperitoneal infection: transfer of peritoneal macrophages to intramuscular sites of infection did not protect adult mice. Rabies virus was phagocytosed by peritoneal macrophages in culture but neither replicated nor induced interferon. Evidence of active intracellular destruction of virus was obscured by thermal inactivation at 37 degrees C. Less inactivation occurred at 33 degrees C. Infected macrophages from suckling mice, but not those from adult mice, spread infection to susceptible cells."} {"id": "PMID:181534", "title": "Analysis of herpesvirus DNA substructure by means of restriction endonucleases.", "content": "The mol. wt. and molar ratios of the Hind III and Hpa I fragments of HSV-1 DNA and the Eco RI fragments of HSV-2 DNA have been determined. Results obtained suggest that DNA isolated from both HSV-1 and HSV-2 consists of molecules with four different sequence arrangements which are present in similar amounts. Our explanation of the cleavage patterns of these four genome arrangements with the different restriction enzymes is presented. Some of the possible implications of these four genome arrangements for genetic recombination are discussed.", "contents": "Analysis of herpesvirus DNA substructure by means of restriction endonucleases. The mol. wt. and molar ratios of the Hind III and Hpa I fragments of HSV-1 DNA and the Eco RI fragments of HSV-2 DNA have been determined. Results obtained suggest that DNA isolated from both HSV-1 and HSV-2 consists of molecules with four different sequence arrangements which are present in similar amounts. Our explanation of the cleavage patterns of these four genome arrangements with the different restriction enzymes is presented. Some of the possible implications of these four genome arrangements for genetic recombination are discussed."} {"id": "PMID:181535", "title": "Transformation of human embryonic fibroblasts by photodynamically inactivated herpes simplex virus, type 2 at supra-optimal temperature.", "content": "Infection of human embryonic fibroblast cell monolayers with neutral red and light-inactivated herpes simplex virus, type 2 (HSV-2) at supra-optimal temperature (42 degrees C) resulted in persistence of viable cells in suspension culture at 37 degrees C which have properties in common with virus transformed cells: formation of cell aggregates, HSV-2-specific antigens and colony formation in soft methyl cellulose medium. These data are consistent with the idea that photodynamic inactivated HSV-2 has potential oncogenic activity.", "contents": "Transformation of human embryonic fibroblasts by photodynamically inactivated herpes simplex virus, type 2 at supra-optimal temperature. Infection of human embryonic fibroblast cell monolayers with neutral red and light-inactivated herpes simplex virus, type 2 (HSV-2) at supra-optimal temperature (42 degrees C) resulted in persistence of viable cells in suspension culture at 37 degrees C which have properties in common with virus transformed cells: formation of cell aggregates, HSV-2-specific antigens and colony formation in soft methyl cellulose medium. These data are consistent with the idea that photodynamic inactivated HSV-2 has potential oncogenic activity."} {"id": "PMID:181536", "title": "Different patterns of polyadenylation of rhinovirus: specified RNA during multiplication in human aneuploid and diploid cells.", "content": "The polyadenylation of rhinovirus-specified RNA in aneuploid HeLa cells and diploid human embryo lung (HEL) cells has been investigated. Polyadenylation occurs at a faster rate and more extensively to virus-specified RNA in infected HEL cells compared with HeLa cells. Poly(A) is added post-transcriptively in both cell types. Furthermore the addition of adenosine or poly(A) during virus multiplication increases the polyadenylation of virus single-stranded RNAs in both cell types, but to a greater extent in HeLa cells.", "contents": "Different patterns of polyadenylation of rhinovirus: specified RNA during multiplication in human aneuploid and diploid cells. The polyadenylation of rhinovirus-specified RNA in aneuploid HeLa cells and diploid human embryo lung (HEL) cells has been investigated. Polyadenylation occurs at a faster rate and more extensively to virus-specified RNA in infected HEL cells compared with HeLa cells. Poly(A) is added post-transcriptively in both cell types. Furthermore the addition of adenosine or poly(A) during virus multiplication increases the polyadenylation of virus single-stranded RNAs in both cell types, but to a greater extent in HeLa cells."} {"id": "PMID:181537", "title": "Monosynaptic reflexes in the superficial forearm flexors in man and their clinical significance.", "content": "Indirect motor responses with the characteristics of the H wave were recorded from the flexor carpi radialis and the palmaris longus muscles in normal adults. A series of experiments has been performed, constituting circumstantial arguments for the monosynaptic nature of these reflex responses. The findings in pathological conditions, which corroborated this point of view, are documented briefly.", "contents": "Monosynaptic reflexes in the superficial forearm flexors in man and their clinical significance. Indirect motor responses with the characteristics of the H wave were recorded from the flexor carpi radialis and the palmaris longus muscles in normal adults. A series of experiments has been performed, constituting circumstantial arguments for the monosynaptic nature of these reflex responses. The findings in pathological conditions, which corroborated this point of view, are documented briefly."} {"id": "PMID:181538", "title": "Ischaemic infarct of the brain stem combined with bisymptomatic Klippel-Tr\u00e9naunay-Weber syndrome and cutis laxa.", "content": "The combination of Klippel-Tr\u00e9naunay-Weber syndrome (KTWS) with intracranial vascular malformations is documented by angiography in a 25 year old man with the classical features of KTWS: systematized naevi, hypertrophy of the right side, and varicosis. In addition, the syndrome was associated with \"cuts laxa\", a coincidence of somar rarity. The patient suffered from an ischaemic infarct of the brain stem with several neurological deficits.", "contents": "Ischaemic infarct of the brain stem combined with bisymptomatic Klippel-Tr\u00e9naunay-Weber syndrome and cutis laxa. The combination of Klippel-Tr\u00e9naunay-Weber syndrome (KTWS) with intracranial vascular malformations is documented by angiography in a 25 year old man with the classical features of KTWS: systematized naevi, hypertrophy of the right side, and varicosis. In addition, the syndrome was associated with \"cuts laxa\", a coincidence of somar rarity. The patient suffered from an ischaemic infarct of the brain stem with several neurological deficits."} {"id": "PMID:181539", "title": "Unusual manifestations of herpes zoster. A clinical and electrophysiological study.", "content": "The literature on complicated herpes zoster is summarized in this paper. The case histories of 18 patients with herpes zoster are presented. Two patients had encephalitis, 2 had myelitis and the other 14 patients had various types of lower motor neurone disturbance. Both patients with encephalitis--one of who developed choreo-athetosis during the illness--recovered fully. Only 1 of the 2 patients with myelitis recovered fully; the other remains severely paraparetic and the reason for her incomplete recovery may be related to the presence of generalized arteriolar disease associated with seronegative rheumatoid disease. One patient developed a Guillain-Barre syndrome 3 weeks after the onset of herpes zoster. Recovery in the 15 patients with lower motor neurone involvement has been slow butcomplete--or almost complete--in all but 1, a patient with persistent facial weakness as part of the Ramsay Hunt syndrome and who also had weakness of one upper limb. Seven other patients had lower limb weakness. In 2 patients the weakness was confined to abdominal myotomes and 2 other patients had urinary retention. Electromyographic abnormalities were found in the muscles which were weak and frequently also in muscles which appeared strong. It is emphasized that neurological disturbances other than sensory abnormalities may be found in patients with herpes zoster. Motor complications of various types are not uncommon.", "contents": "Unusual manifestations of herpes zoster. A clinical and electrophysiological study. The literature on complicated herpes zoster is summarized in this paper. The case histories of 18 patients with herpes zoster are presented. Two patients had encephalitis, 2 had myelitis and the other 14 patients had various types of lower motor neurone disturbance. Both patients with encephalitis--one of who developed choreo-athetosis during the illness--recovered fully. Only 1 of the 2 patients with myelitis recovered fully; the other remains severely paraparetic and the reason for her incomplete recovery may be related to the presence of generalized arteriolar disease associated with seronegative rheumatoid disease. One patient developed a Guillain-Barre syndrome 3 weeks after the onset of herpes zoster. Recovery in the 15 patients with lower motor neurone involvement has been slow butcomplete--or almost complete--in all but 1, a patient with persistent facial weakness as part of the Ramsay Hunt syndrome and who also had weakness of one upper limb. Seven other patients had lower limb weakness. In 2 patients the weakness was confined to abdominal myotomes and 2 other patients had urinary retention. Electromyographic abnormalities were found in the muscles which were weak and frequently also in muscles which appeared strong. It is emphasized that neurological disturbances other than sensory abnormalities may be found in patients with herpes zoster. Motor complications of various types are not uncommon."} {"id": "PMID:181540", "title": "Dysmyelination in the sciatic nerves of dystrophic mice.", "content": "Ultrastructural alterations were observed in the sciatic nerve of dystrophic mice. Myelin sheaths were abnormal in shape, abruptly ceased beyond a node of Ranvier, leaving the axon naked. These changes were seen in both afferent and efferent nerve fibres. Apparent embryonal Schwann cells and Schwann cells which were associated with increased lysosomes in the cytoplasm were observed in the proximal portion. There is a relative decrease in Schwann cells in the cross-section of the radicular parts, and a relative increase in the distal parts. The mean number of neurotubules per unit area was smaller while the mean number of the neurofilaments was larger in U-axons, in the dystrophic mice than in the controls. In M-fibres, neurotubules and neurofilaments showed no significant difference between systrophic and control mice.", "contents": "Dysmyelination in the sciatic nerves of dystrophic mice. Ultrastructural alterations were observed in the sciatic nerve of dystrophic mice. Myelin sheaths were abnormal in shape, abruptly ceased beyond a node of Ranvier, leaving the axon naked. These changes were seen in both afferent and efferent nerve fibres. Apparent embryonal Schwann cells and Schwann cells which were associated with increased lysosomes in the cytoplasm were observed in the proximal portion. There is a relative decrease in Schwann cells in the cross-section of the radicular parts, and a relative increase in the distal parts. The mean number of neurotubules per unit area was smaller while the mean number of the neurofilaments was larger in U-axons, in the dystrophic mice than in the controls. In M-fibres, neurotubules and neurofilaments showed no significant difference between systrophic and control mice."} {"id": "PMID:181541", "title": "Probability of conduction deficit as related to fiber length in random-distribution models of peripheral neuropathies.", "content": "This paper presents a set of probabilistic models which reproduce the proximodistal gradient of sensory deficit in peripheral neuropathies, on the basis of the occurrence of axonal dysfunction as a result of randomly distributed abnormalities. The models, which are based on conduction block, loss of temporal coherence, and weak interactions between nerve fibers, demonstrate that randomly distributed axonal dysfunction provides a sufficient condition for distal sensory deficit. The models predict a marked reduction in the length for normal sensory conduction with small increases in the probability of axomal dysfunction, providing a possible correlate for the rapid clinical progression of some neuropathies. The hypothesis that weak interactions between fibers result in paresthesiae in peripheral neuropathies is also discussed.", "contents": "Probability of conduction deficit as related to fiber length in random-distribution models of peripheral neuropathies. This paper presents a set of probabilistic models which reproduce the proximodistal gradient of sensory deficit in peripheral neuropathies, on the basis of the occurrence of axonal dysfunction as a result of randomly distributed abnormalities. The models, which are based on conduction block, loss of temporal coherence, and weak interactions between nerve fibers, demonstrate that randomly distributed axonal dysfunction provides a sufficient condition for distal sensory deficit. The models predict a marked reduction in the length for normal sensory conduction with small increases in the probability of axomal dysfunction, providing a possible correlate for the rapid clinical progression of some neuropathies. The hypothesis that weak interactions between fibers result in paresthesiae in peripheral neuropathies is also discussed."} {"id": "PMID:181542", "title": "Relative strength of synaptic input from short-latency pathways to motor units of defined type in cat medial gastrocnemius.", "content": "1. Intracellular recording and stimulation techniques were used in anesthetized cats to study the interrelations between amplitudes of PSPs produced by electrical stimulation of several short-latency pathways to MG alpha motoneurons and the mechanical properties of muscle units innervated by the same cells. Motor-unit types were identified by muscle-unit properties.2. The maximum amplitudes of monosynaptic EPSPs produced in MG motoneurons by activation of homonymous (MG) and heteronymous (LGS) group Ia afferents were clearly related to motor-unit type, being, on the average, largest in type S units, somewhat smaller in type FR and F(int) units, and smallest in type FF units. Correspondingly, group Ia EPSP amplitudes were inversely correlated with muscle-unit tension production and directly correlated with resistance to fatigue. The same input distribution was true for disynaptic IPSPs produced by group Ia afferents from antagonist ankle flexors.3. The amplitudes of monosynaptic EPSPs produced by fibers descending in the ipsilateral ventral funiculi of the low thoracic cord were not clearly related to MG motor-unit type or (therefore) to muscle-unit properties.4. A quantitative input-output model of the MG motor-unit pool, based in part on the present results, suggests that overall characteristics of MG motor units, and their relative numbers in the MG pool, reflect functional specializations determined by specific mechanical demands placed on the MG muscle by the usual motor behavior of the animal.", "contents": "Relative strength of synaptic input from short-latency pathways to motor units of defined type in cat medial gastrocnemius. 1. Intracellular recording and stimulation techniques were used in anesthetized cats to study the interrelations between amplitudes of PSPs produced by electrical stimulation of several short-latency pathways to MG alpha motoneurons and the mechanical properties of muscle units innervated by the same cells. Motor-unit types were identified by muscle-unit properties.2. The maximum amplitudes of monosynaptic EPSPs produced in MG motoneurons by activation of homonymous (MG) and heteronymous (LGS) group Ia afferents were clearly related to motor-unit type, being, on the average, largest in type S units, somewhat smaller in type FR and F(int) units, and smallest in type FF units. Correspondingly, group Ia EPSP amplitudes were inversely correlated with muscle-unit tension production and directly correlated with resistance to fatigue. The same input distribution was true for disynaptic IPSPs produced by group Ia afferents from antagonist ankle flexors.3. The amplitudes of monosynaptic EPSPs produced by fibers descending in the ipsilateral ventral funiculi of the low thoracic cord were not clearly related to MG motor-unit type or (therefore) to muscle-unit properties.4. A quantitative input-output model of the MG motor-unit pool, based in part on the present results, suggests that overall characteristics of MG motor units, and their relative numbers in the MG pool, reflect functional specializations determined by specific mechanical demands placed on the MG muscle by the usual motor behavior of the animal."} {"id": "PMID:181543", "title": "Rhythmic hyperpolarizations and depolarization of sympathetic ganglion cells induced by caffeine.", "content": "Superfusion of the isolated sympathetic ganglion of the bullfrog with a caffeine-containing (1-6 mM) solution caused in many cells an initial slow hyperpolarization which was followed by a subliminal depolarization interruped by rhythmic hyperpolarizations. A hyperpolarization, similar to one of the rhythmic hyperpolarizations, could be triggered by an action potential in the presence of caffeine. The action potential itself was not markedly affected by caffeine except for its afterhyperpolarization which was prolonged. All these caffeine-induced hyperpolarizations were associated with a marked reduction of the membrane resistance, their amplitude was increased in a K+-free solution and decreased in a high-K+ solution, and their polarity was reversed at the same level at which the afterhyperpolarization was also inverted. This reversal level was not altered by omission of Na+ or C1- from the external medium. These hyperpolarizations were reversibly abolished by depletion of external Ca2+ or replacement of external Ca2+ by Mg2+. Excess of external Ca2+ caused a shortening of the interval between rhythmic hyperpolarizations. Furthermore, iontophoretic injection of EDTA into the cytoplasm markedly depressed the initial caffeine hyperpolarizatin and abolished both the rhythmic and evoked caffeine hyperpolarizations. The caffeine-induced depolarization was not affected by omission of external Cl-. It was decreased in a Na+-free medium, but completely eliminated by omission of both Na+ and Ca2+ from the external medium. Tetrodotoxin did not impair the production of the initial and the rhythmic hyperpolarizations. A strong depolarizing pulse could evoke a typical hyperpolarizing response in the presence of this compound. Dibutyryl cyclic AMP, d-tubocurarine, atropine, and phenoxybenzamine were without effect on the caffeine-induced hyperpolarizations and depolarization. It was concluded that each caffeine-induced hyperpolarization is the result of an increased K+ permeability, which is probably caused by a rise in the internal Ca2+ concentration. It was also concluded that the caffeine-induced depolarization is due to an increased membrane permeability to Ca2+ and Na+.", "contents": "Rhythmic hyperpolarizations and depolarization of sympathetic ganglion cells induced by caffeine. Superfusion of the isolated sympathetic ganglion of the bullfrog with a caffeine-containing (1-6 mM) solution caused in many cells an initial slow hyperpolarization which was followed by a subliminal depolarization interruped by rhythmic hyperpolarizations. A hyperpolarization, similar to one of the rhythmic hyperpolarizations, could be triggered by an action potential in the presence of caffeine. The action potential itself was not markedly affected by caffeine except for its afterhyperpolarization which was prolonged. All these caffeine-induced hyperpolarizations were associated with a marked reduction of the membrane resistance, their amplitude was increased in a K+-free solution and decreased in a high-K+ solution, and their polarity was reversed at the same level at which the afterhyperpolarization was also inverted. This reversal level was not altered by omission of Na+ or C1- from the external medium. These hyperpolarizations were reversibly abolished by depletion of external Ca2+ or replacement of external Ca2+ by Mg2+. Excess of external Ca2+ caused a shortening of the interval between rhythmic hyperpolarizations. Furthermore, iontophoretic injection of EDTA into the cytoplasm markedly depressed the initial caffeine hyperpolarizatin and abolished both the rhythmic and evoked caffeine hyperpolarizations. The caffeine-induced depolarization was not affected by omission of external Cl-. It was decreased in a Na+-free medium, but completely eliminated by omission of both Na+ and Ca2+ from the external medium. Tetrodotoxin did not impair the production of the initial and the rhythmic hyperpolarizations. A strong depolarizing pulse could evoke a typical hyperpolarizing response in the presence of this compound. Dibutyryl cyclic AMP, d-tubocurarine, atropine, and phenoxybenzamine were without effect on the caffeine-induced hyperpolarizations and depolarization. It was concluded that each caffeine-induced hyperpolarization is the result of an increased K+ permeability, which is probably caused by a rise in the internal Ca2+ concentration. It was also concluded that the caffeine-induced depolarization is due to an increased membrane permeability to Ca2+ and Na+."} {"id": "PMID:181544", "title": "Assessment of effect of starvation, glucose, fatty acids and hormones on alpha-decarboxylation of leucine in skeletal muscle of rat.", "content": "The present investigations of rates of oxidation of [U-14C] or [1-14C]leucine by homogenates of gastrocnemius muscle of fed and starved rats have indicated that 14CO2 production is mainly the result of alpha-decarboxylation of leucine in this tissue. This incomplete oxidation was not the result of imparied tricarboxylic acid cycle since the oxidation of palmitate proceeded to completion within the experimental conditions. In the subsequent studies, the effect of altered nutrition and metabolic factors on alpha-decarboxylation of leucine by gastrocnemius muscle homogenates was investigated. Starvation increased the rate of alpha-decarboxylation of leucine. Glucose or palmitate (C16) added in physiological concentrations to the incubation medium were without effect on decarboxylation of leucine, but this reaction was stimulated by addition of 1 mM hexanoate (C6) or octanoate (C8) to the incubation medium. However, when fatty acid chain length was elongated to C10 (decanoate), the stimulatory effect was not only abolished, but this fatty acid significantly inhibited the rate of leucine decarboxylation. Addition of insulin, epinephrine, glucagon and cyclic AMP within a wide range of concentrations to the incubation medium did not significantly affect the rate of decarboxylation of leucine. These studies indicate a complex interrelationship between the metabolism of leucine and that of fatty acids.", "contents": "Assessment of effect of starvation, glucose, fatty acids and hormones on alpha-decarboxylation of leucine in skeletal muscle of rat. The present investigations of rates of oxidation of [U-14C] or [1-14C]leucine by homogenates of gastrocnemius muscle of fed and starved rats have indicated that 14CO2 production is mainly the result of alpha-decarboxylation of leucine in this tissue. This incomplete oxidation was not the result of imparied tricarboxylic acid cycle since the oxidation of palmitate proceeded to completion within the experimental conditions. In the subsequent studies, the effect of altered nutrition and metabolic factors on alpha-decarboxylation of leucine by gastrocnemius muscle homogenates was investigated. Starvation increased the rate of alpha-decarboxylation of leucine. Glucose or palmitate (C16) added in physiological concentrations to the incubation medium were without effect on decarboxylation of leucine, but this reaction was stimulated by addition of 1 mM hexanoate (C6) or octanoate (C8) to the incubation medium. However, when fatty acid chain length was elongated to C10 (decanoate), the stimulatory effect was not only abolished, but this fatty acid significantly inhibited the rate of leucine decarboxylation. Addition of insulin, epinephrine, glucagon and cyclic AMP within a wide range of concentrations to the incubation medium did not significantly affect the rate of decarboxylation of leucine. These studies indicate a complex interrelationship between the metabolism of leucine and that of fatty acids."} {"id": "PMID:181545", "title": "Rat strain differences in cyclic-AMP levels in liver and epididymal fat pad tissue as influenced by glucagon.", "content": "A glucagon-saline solution (0.1 ml, 10(7) mole/100 g body weight) was injected via the portal vein into nonfasted Wistar and carbohydrate-sensitive BHE rats. Levels of liver and epididymal fat pad cyclic-AMP were observed after 6 and 24 minutes. When compared to sham injected rats at 6 minutes, glucagon injected rats of both strains had twice the level of cyclie-AMP in liver and fat pad tissue. By 24 minutes, the cyclic-AMP levels of the Wistar rats had decreased to those observed in their sham injected counterparts, and the concentration of liver cyclic-AMP in both sham injected and glucagon injected BHE rats had decreased to levels significantly below those observed in the Wistar rats. This observation suggests that a lipolytic-lipogenic imbalance may reside in the livers of rats of the BHE strain.", "contents": "Rat strain differences in cyclic-AMP levels in liver and epididymal fat pad tissue as influenced by glucagon. A glucagon-saline solution (0.1 ml, 10(7) mole/100 g body weight) was injected via the portal vein into nonfasted Wistar and carbohydrate-sensitive BHE rats. Levels of liver and epididymal fat pad cyclic-AMP were observed after 6 and 24 minutes. When compared to sham injected rats at 6 minutes, glucagon injected rats of both strains had twice the level of cyclie-AMP in liver and fat pad tissue. By 24 minutes, the cyclic-AMP levels of the Wistar rats had decreased to those observed in their sham injected counterparts, and the concentration of liver cyclic-AMP in both sham injected and glucagon injected BHE rats had decreased to levels significantly below those observed in the Wistar rats. This observation suggests that a lipolytic-lipogenic imbalance may reside in the livers of rats of the BHE strain."} {"id": "PMID:181547", "title": "Urinary proteins in occupational exposure to chemicals and in diseases.", "content": "Isoelectric focusing in thin-layer polyacrylamide gel is a method with high resolving power, e.g. for urinary proteins. Therefore more information can be obtained with this method than with ordinary electrophoresis. The present version of the method has a high capacity and allows study of up to 25 samples in parallel on each gel. Only a little more than one hour is required for separation. A sensitive staining procedure is used which allows detection of as little as 0.1 mug of protein in each zone. When effects on the kidney are present more than 20 different protein zones can sometimes be separated. Evaluation is made by densitometry as well as by comparison and classification of patterns. Urine samples have been studied from workers with varying exposure to cadmium lead and various chlorinated hydrocarbons, and patients with glomerulonephritis, pyelonephritis, nephrosis and mixed tubular and glomerular diseases. Typical tubular patterns, i.e. as developed in association with cadmium exposure were characterized by elevated excretion of beta1-microglobulin. Other types of kidney malfunction showed different features.", "contents": "Urinary proteins in occupational exposure to chemicals and in diseases. Isoelectric focusing in thin-layer polyacrylamide gel is a method with high resolving power, e.g. for urinary proteins. Therefore more information can be obtained with this method than with ordinary electrophoresis. The present version of the method has a high capacity and allows study of up to 25 samples in parallel on each gel. Only a little more than one hour is required for separation. A sensitive staining procedure is used which allows detection of as little as 0.1 mug of protein in each zone. When effects on the kidney are present more than 20 different protein zones can sometimes be separated. Evaluation is made by densitometry as well as by comparison and classification of patterns. Urine samples have been studied from workers with varying exposure to cadmium lead and various chlorinated hydrocarbons, and patients with glomerulonephritis, pyelonephritis, nephrosis and mixed tubular and glomerular diseases. Typical tubular patterns, i.e. as developed in association with cadmium exposure were characterized by elevated excretion of beta1-microglobulin. Other types of kidney malfunction showed different features."} {"id": "PMID:181548", "title": "Arteriography in oral and maxillofacial surgery.", "content": "A brief review of the methodology of selective external carotid arteriography is presented together with its risks, complications, and contraindications. The indications for this procedure are described with illustrative case material to demonstrate its usefulness in both diagnosis and preoperative evaluation of various types of lesions of the head and neck that may be encountered in the practice of oral and maxillofacial surgery.", "contents": "Arteriography in oral and maxillofacial surgery. A brief review of the methodology of selective external carotid arteriography is presented together with its risks, complications, and contraindications. The indications for this procedure are described with illustrative case material to demonstrate its usefulness in both diagnosis and preoperative evaluation of various types of lesions of the head and neck that may be encountered in the practice of oral and maxillofacial surgery."} {"id": "PMID:181549", "title": "Hepatitis type A in an oral surgeon: a prospective study of contacts.", "content": "No acute cases of clinical or anicteric hepatitis were in observed in 75% of 161 patients who had been exposed to hepatitis A by an oral surgeon during the contagious period. Three cases of liver dysfunction of indeterminate cause did occur, although at least two could be attributed to multiple abuses of drugs 3-5 and not to exposure to hepatitis. The fact that hepatitis A did not spread in this instance suggests that oral surgeons who are ill with acute hepatitis A do not necessarily transmit the disease to their patients. Epidemiologic investigations of similar situations will undoubtedly augment this preliminary data.", "contents": "Hepatitis type A in an oral surgeon: a prospective study of contacts. No acute cases of clinical or anicteric hepatitis were in observed in 75% of 161 patients who had been exposed to hepatitis A by an oral surgeon during the contagious period. Three cases of liver dysfunction of indeterminate cause did occur, although at least two could be attributed to multiple abuses of drugs 3-5 and not to exposure to hepatitis. The fact that hepatitis A did not spread in this instance suggests that oral surgeons who are ill with acute hepatitis A do not necessarily transmit the disease to their patients. Epidemiologic investigations of similar situations will undoubtedly augment this preliminary data."} {"id": "PMID:181550", "title": "Melanotic neuroectodermal tumor of infancy.", "content": "A case of pigmented neuroectodermal tumor (melanotic progonoma) of the maxilla is presented. The treatment of this tumor is conservative surgical excision since the likelihood of recurrence is extremely slight. No case has ever been reported in which tumor metastasized.", "contents": "Melanotic neuroectodermal tumor of infancy. A case of pigmented neuroectodermal tumor (melanotic progonoma) of the maxilla is presented. The treatment of this tumor is conservative surgical excision since the likelihood of recurrence is extremely slight. No case has ever been reported in which tumor metastasized."} {"id": "PMID:181552", "title": "Histopathologic study of the liver in the early cholestatic phase of alpha-1-antitrypsin deficiency.", "content": "Liver biopsies obtained during the first six months of life were studied in 15 children who had prolonged neonatal cholestasis and alpha-1-antitrypsin deficiency (Pi ZZ). Intracellular PAS-positive globules were always observed, even during the first months of life. At this early stage of the disease, three morphologic patterns of hepatic alteration were distinguished. Group 1: six cases with cholestasis, hepatocellular damage, and slight portal fibrosis; Group 2: five cases with important portal fibrosis and bile duct proliferation; and Group 3: four cases in which ductular hypoplasia was the main feature. A correlation between histologic patterns and clinical course may be established: improvement of liver injury in Group 1, early cirrhosis in Group 2, and prolonged cholestasis in Group 3. The natural evolution of the disease appears to be different in each of the three groups.", "contents": "Histopathologic study of the liver in the early cholestatic phase of alpha-1-antitrypsin deficiency. Liver biopsies obtained during the first six months of life were studied in 15 children who had prolonged neonatal cholestasis and alpha-1-antitrypsin deficiency (Pi ZZ). Intracellular PAS-positive globules were always observed, even during the first months of life. At this early stage of the disease, three morphologic patterns of hepatic alteration were distinguished. Group 1: six cases with cholestasis, hepatocellular damage, and slight portal fibrosis; Group 2: five cases with important portal fibrosis and bile duct proliferation; and Group 3: four cases in which ductular hypoplasia was the main feature. A correlation between histologic patterns and clinical course may be established: improvement of liver injury in Group 1, early cirrhosis in Group 2, and prolonged cholestasis in Group 3. The natural evolution of the disease appears to be different in each of the three groups."} {"id": "PMID:181555", "title": "Enzymatic penetration through intact sulcular epithelium.", "content": "To explore possible enzymatic penetration through intact sulcular epithelium tritium labeled hyaluronidase and collagenase were applied to the gingival sulcus of five white lip marmosets. One quadrant per monkey remained untreated. Each remaining quadrant was randomly assigned to one of the following modalities of application: (a) tritiated hyaluronidase, (b) tritiated collagenase, (c) unlabeled hyaluronidase followed by tritiated collagenase, (d) inactivated tritiated hyaluronidase, or (e) normal saline as experimental controls. The enzymes were applied by means of a Pasteur disposable pipette. Eight drops were administered over a 4-minute period, one every 30 seconds. After a 5-minute waiting period a second series of eight applications was given over a 4-minute period. Radioautographic and standard histologic materials were obtained. Results suggest that: 1. Hyaluronidase has the ability to penetrate through intact nonkeratinized sulcular epithelium, widening the intercellular epithelial spaces and disorganizing the connective tissue ground substance. 2. Collagenase per se does not have the ability to penetrate through the intact sulcular epithelium. Its effect remains confined only to the superficial layers of the epithelium. 3. However, when collagenase application is preceded by hyaluronidase, collagenase spreads easily through the epithelium and deeply into the connective tissue. Hyaluronidase acts unquestionably as a spreading factors.", "contents": "Enzymatic penetration through intact sulcular epithelium. To explore possible enzymatic penetration through intact sulcular epithelium tritium labeled hyaluronidase and collagenase were applied to the gingival sulcus of five white lip marmosets. One quadrant per monkey remained untreated. Each remaining quadrant was randomly assigned to one of the following modalities of application: (a) tritiated hyaluronidase, (b) tritiated collagenase, (c) unlabeled hyaluronidase followed by tritiated collagenase, (d) inactivated tritiated hyaluronidase, or (e) normal saline as experimental controls. The enzymes were applied by means of a Pasteur disposable pipette. Eight drops were administered over a 4-minute period, one every 30 seconds. After a 5-minute waiting period a second series of eight applications was given over a 4-minute period. Radioautographic and standard histologic materials were obtained. Results suggest that: 1. Hyaluronidase has the ability to penetrate through intact nonkeratinized sulcular epithelium, widening the intercellular epithelial spaces and disorganizing the connective tissue ground substance. 2. Collagenase per se does not have the ability to penetrate through the intact sulcular epithelium. Its effect remains confined only to the superficial layers of the epithelium. 3. However, when collagenase application is preceded by hyaluronidase, collagenase spreads easily through the epithelium and deeply into the connective tissue. Hyaluronidase acts unquestionably as a spreading factors."} {"id": "PMID:181557", "title": "Studies on tolerance development to single doses of morphine in mice.", "content": "Single-dose tolerance to the antinociceptive effect of morphine can be demonstrated using an adequate initial priming dose of morphine and allowing an interval of 48 to 72 hours for its development. The threshold dose necessary to produce tolerance was found to be about 3 to 4 times greater than that for producing analgesia but higher doses of morphine did not enhance further tolerance development. Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine. Cross-tolerance was evidenced by a decrease in analgetic response to methadone 3 days after a single priming dose of morphine and a decrease in morphine response after a single dose of methadone. The development of single-dose tolerance was inhibited by cycloheximide. Single-dose tolerance was also blocked by 5,6-dihydroxytryptamine and perhaps enhanced by L-tryptophan. Cyclic 3',5'-adensine monophosphate did not affect single-dose tolerance development significantly although the direction was in favor of augmentation. Morphine uptake by the brain was not modified by the development of single-dose tolerance. Physical dependence, as measured by naloxone-precipitated withdrawal jumping, was not observed when single-dose analgetic tolerance was maximal. The results suggest that single-dose tolerance to morphine involves the synthesis of some macromolecule and support previous findings in this laboratroy involving an association with serotonin.", "contents": "Studies on tolerance development to single doses of morphine in mice. Single-dose tolerance to the antinociceptive effect of morphine can be demonstrated using an adequate initial priming dose of morphine and allowing an interval of 48 to 72 hours for its development. The threshold dose necessary to produce tolerance was found to be about 3 to 4 times greater than that for producing analgesia but higher doses of morphine did not enhance further tolerance development. Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine. Cross-tolerance was evidenced by a decrease in analgetic response to methadone 3 days after a single priming dose of morphine and a decrease in morphine response after a single dose of methadone. The development of single-dose tolerance was inhibited by cycloheximide. Single-dose tolerance was also blocked by 5,6-dihydroxytryptamine and perhaps enhanced by L-tryptophan. Cyclic 3',5'-adensine monophosphate did not affect single-dose tolerance development significantly although the direction was in favor of augmentation. Morphine uptake by the brain was not modified by the development of single-dose tolerance. Physical dependence, as measured by naloxone-precipitated withdrawal jumping, was not observed when single-dose analgetic tolerance was maximal. The results suggest that single-dose tolerance to morphine involves the synthesis of some macromolecule and support previous findings in this laboratroy involving an association with serotonin."} {"id": "PMID:181558", "title": "Regulation of cyclic nucleotide levels and glycogen phosphorylase activity by acetylcholine and epinephrine in perfused rat hearts.", "content": "Acetylcholine (ACh) produced a time and dose-dependent increase in cyclic 3',5'-guanosine monophosphate (cyclic GMP) levels in perfused rat hearts without any significant (P greater than .05) change in cyclic 3',5'-adensoine monophosphate (cyclic AMP) level or glycogen phosphorylase activity. Epinephrine produced a dose-dependent increase in both cyclin AMP and phosphorylase activity but no significant (P greater than .05) change in cyclic GMP levels. When ACh (10(-6) M) was infused into hearts during the infusion of epinephrine (10(-6) M), a time-dependent increase in cyclic GMP and decrease in cyclic AMP occurred, both of which preceded a significant (P less than .05) decrease in glycogen phosphorylase activity. In epinephrine-stimulated hearts, ACh produced a dose-dependent increase in cyclic GMP levels. Similar concentrations produced a fall in cyclic AMP levels and phosphorylase activity. No condition tested resulted in a significant (P greater than .05) change in glycogen synthase activity. It is concluded that ACh can reduce cyclic AMP levels and phosphorylase activity only when they have been elevated above basal values. These changes are associated with an increase in cyclic GMP. The reduction in phosphorylase produced by ACh may be the result of either or both of the changes in cyclic nucleotide levels.", "contents": "Regulation of cyclic nucleotide levels and glycogen phosphorylase activity by acetylcholine and epinephrine in perfused rat hearts. Acetylcholine (ACh) produced a time and dose-dependent increase in cyclic 3',5'-guanosine monophosphate (cyclic GMP) levels in perfused rat hearts without any significant (P greater than .05) change in cyclic 3',5'-adensoine monophosphate (cyclic AMP) level or glycogen phosphorylase activity. Epinephrine produced a dose-dependent increase in both cyclin AMP and phosphorylase activity but no significant (P greater than .05) change in cyclic GMP levels. When ACh (10(-6) M) was infused into hearts during the infusion of epinephrine (10(-6) M), a time-dependent increase in cyclic GMP and decrease in cyclic AMP occurred, both of which preceded a significant (P less than .05) decrease in glycogen phosphorylase activity. In epinephrine-stimulated hearts, ACh produced a dose-dependent increase in cyclic GMP levels. Similar concentrations produced a fall in cyclic AMP levels and phosphorylase activity. No condition tested resulted in a significant (P greater than .05) change in glycogen synthase activity. It is concluded that ACh can reduce cyclic AMP levels and phosphorylase activity only when they have been elevated above basal values. These changes are associated with an increase in cyclic GMP. The reduction in phosphorylase produced by ACh may be the result of either or both of the changes in cyclic nucleotide levels."} {"id": "PMID:181559", "title": "Blockade by amino acid antagonists of neuronal excitation mediated by the pyramidal tract.", "content": "1. The responses to glutamate and amino acid antagonists of cells in the cuneate nucleus of anaesthetized rats have been examined.2. 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethylester applied by micro-iontophoresis reduced glutamate excitation of the neurons. HA-966 WAS EFFECTIVE ON MORE CELLS THAN GLUTAMIC ACID DIETHYLESTER AND WAS MORE POTENT. HA-966 DID NOT AFFECT EXCITATORY RESPONSES TO ACETYLCHOLINE.3. Spike activity of cuneate cells was evoked by stimulating the cerebral cortex. Spikeswhich could be attributed to monosynaptic activation of the cells were studied. The pyramidal tract is the only corticofugal pathway known to be capable of short latency activation of dorsal column nucleus neurones.4. HA-966 reversibly blocked the evoked activity in twenty-eight (70%) of forty units in which monosynaptically evoked spikes were induced.5. The results raise the possibility that the neurotransmitter released by neurones of the pyramidal tract may be an excitatory amino acid.", "contents": "Blockade by amino acid antagonists of neuronal excitation mediated by the pyramidal tract. 1. The responses to glutamate and amino acid antagonists of cells in the cuneate nucleus of anaesthetized rats have been examined.2. 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethylester applied by micro-iontophoresis reduced glutamate excitation of the neurons. HA-966 WAS EFFECTIVE ON MORE CELLS THAN GLUTAMIC ACID DIETHYLESTER AND WAS MORE POTENT. HA-966 DID NOT AFFECT EXCITATORY RESPONSES TO ACETYLCHOLINE.3. Spike activity of cuneate cells was evoked by stimulating the cerebral cortex. Spikeswhich could be attributed to monosynaptic activation of the cells were studied. The pyramidal tract is the only corticofugal pathway known to be capable of short latency activation of dorsal column nucleus neurones.4. HA-966 reversibly blocked the evoked activity in twenty-eight (70%) of forty units in which monosynaptically evoked spikes were induced.5. The results raise the possibility that the neurotransmitter released by neurones of the pyramidal tract may be an excitatory amino acid."} {"id": "PMID:181560", "title": "Cholinergic motor neurones in the stomatogastric system of the lobster.", "content": "1. A study of the neurotransmitters used by each of the eleven types of excitatory motor neurones (identified according to the muscle innervated) of the lobster stomatogastric ganglion was undertaken. 2. The dorsal dilator muscle is innervated by the two motor neurones designated 'PD'. Bath and iontophoretic applications of acetylcholine (ACh) produce contractures and depolarizations respectively in the dorsal dilator muscle. 3. Pharmacological experiments support the cholinergic nature of the excitatory junctional potentials (e.j.p.s) recorded in the dorsal dilator muscle when the PD motor nerve is stimulated. 4. The apparent reversal potentials for the e.j.p.s and the iontophoretic ACh response in the dorsal dilator muscle are the same. 5. On the basis of choline acetyltransferase assays on identified stomatogastric ganglion motor neurone somata and tension measurements on the muscles innervated by each type of stomatogastric ganglion motor neurone, a transmitter candidate was established for each type of motor neurone. Motor neurones named VD, LPG, GM, MG, LG, and DG are putatively cholinergic. L-Glutamate is a transmitter candidate for the motor neurones called LP, PY, IC, and AM. 6. Potential correlations between the distribution of putatively cholinergic and glutaminergic motor neurones and the electrical coupling among the stomatogastric ganglion motor neurones are discussed.", "contents": "Cholinergic motor neurones in the stomatogastric system of the lobster. 1. A study of the neurotransmitters used by each of the eleven types of excitatory motor neurones (identified according to the muscle innervated) of the lobster stomatogastric ganglion was undertaken. 2. The dorsal dilator muscle is innervated by the two motor neurones designated 'PD'. Bath and iontophoretic applications of acetylcholine (ACh) produce contractures and depolarizations respectively in the dorsal dilator muscle. 3. Pharmacological experiments support the cholinergic nature of the excitatory junctional potentials (e.j.p.s) recorded in the dorsal dilator muscle when the PD motor nerve is stimulated. 4. The apparent reversal potentials for the e.j.p.s and the iontophoretic ACh response in the dorsal dilator muscle are the same. 5. On the basis of choline acetyltransferase assays on identified stomatogastric ganglion motor neurone somata and tension measurements on the muscles innervated by each type of stomatogastric ganglion motor neurone, a transmitter candidate was established for each type of motor neurone. Motor neurones named VD, LPG, GM, MG, LG, and DG are putatively cholinergic. L-Glutamate is a transmitter candidate for the motor neurones called LP, PY, IC, and AM. 6. Potential correlations between the distribution of putatively cholinergic and glutaminergic motor neurones and the electrical coupling among the stomatogastric ganglion motor neurones are discussed."} {"id": "PMID:181561", "title": "Mode of stimulation by adenosine 3':5'-cyclic monophosphate of the sodium efflux in barnacle muscle fibres.", "content": "1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(-6)M, when micro-injected, causes a sharp rise in the radio-Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre-injecting 100 or 500 mM-EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre-injecting the protein inhibitor of Walsh and practically abolished by pre-injecting 500 mM-EGTA and soaking in Ca-free artificial sea water, ASW. 5. The Ca2+-independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+-free, Li+-ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain-insensitive Na efflux into HEPES-Ca2+-free ASW at pH 6-3. These same fibres show a marked response to cAMP. (II) The ouabain-insensitive Na efflux into HCO3-, Ca2+-free ASW from fibres pre-treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2-sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain-insensitive Na efflux into HCO-3, Ca2+-free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP-dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon.", "contents": "Mode of stimulation by adenosine 3':5'-cyclic monophosphate of the sodium efflux in barnacle muscle fibres. 1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(-6)M, when micro-injected, causes a sharp rise in the radio-Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre-injecting 100 or 500 mM-EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre-injecting the protein inhibitor of Walsh and practically abolished by pre-injecting 500 mM-EGTA and soaking in Ca-free artificial sea water, ASW. 5. The Ca2+-independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+-free, Li+-ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain-insensitive Na efflux into HEPES-Ca2+-free ASW at pH 6-3. These same fibres show a marked response to cAMP. (II) The ouabain-insensitive Na efflux into HCO3-, Ca2+-free ASW from fibres pre-treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2-sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain-insensitive Na efflux into HCO-3, Ca2+-free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP-dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon."} {"id": "PMID:181562", "title": "The effect of calcium ions on the binomial statistic parameters that control acetylcholine release at preganglionic nerve terminals.", "content": "1. A study has been made of the effects of changing [Ca]O and [Mg]O on the binomial statistic parameters p and n that control the average quantal content (m) of the excitatory post-synaptic potential (e.p.s.p.) due to acetylcholine release at preganglionic nerve terminals. 2. When [Ca]O was increased in the range from 0-2 to 0-5 mM, p increased as the first power of [Ca]O whereas n increased as the 0-5 power of [Ca]O; when [Mg]O was increased in the range from 5 to 200 mM, p decreased as the first power of [Mg]O whereas n decreased as the 0-5 power of [Mg]O. 3. The increase in quantal release of a test impulse following a conditioning impulse was primarily due to an increase in n; the increase in quantal content of successive e.p.s.p.s in a short train was due to an increase in n and p, and the increase in n was quantitatively described in terms of the accumulation of a Ca-receptor complex in the nerve terminal. 4. The decrease in quantal content of successive e.p.s.p.s during long trains of impulses over several minutes was primarily due to a decrease in n. These results are discussed in terms of an hypothesis concerning the physical basis of n and p in the release process.", "contents": "The effect of calcium ions on the binomial statistic parameters that control acetylcholine release at preganglionic nerve terminals. 1. A study has been made of the effects of changing [Ca]O and [Mg]O on the binomial statistic parameters p and n that control the average quantal content (m) of the excitatory post-synaptic potential (e.p.s.p.) due to acetylcholine release at preganglionic nerve terminals. 2. When [Ca]O was increased in the range from 0-2 to 0-5 mM, p increased as the first power of [Ca]O whereas n increased as the 0-5 power of [Ca]O; when [Mg]O was increased in the range from 5 to 200 mM, p decreased as the first power of [Mg]O whereas n decreased as the 0-5 power of [Mg]O. 3. The increase in quantal release of a test impulse following a conditioning impulse was primarily due to an increase in n; the increase in quantal content of successive e.p.s.p.s in a short train was due to an increase in n and p, and the increase in n was quantitatively described in terms of the accumulation of a Ca-receptor complex in the nerve terminal. 4. The decrease in quantal content of successive e.p.s.p.s during long trains of impulses over several minutes was primarily due to a decrease in n. These results are discussed in terms of an hypothesis concerning the physical basis of n and p in the release process."} {"id": "PMID:181563", "title": "Induction of cholinergic enzymes in chick ciliary ganglion and iris muscle cells during synapse formation.", "content": "1. In chick ciliary ganglia and irises, cholineacetyltransferase (ChAc) and acetylcholinesterase (AChE) activities were measured from the fifth day of incubation until 1 week after hatching. The changes in enzyme activity were correlated in time with previous electrophysiological and morphological findings of synapse formation in these tissues. 2. At Stage 26 (Hamburger & Hamilton, 1951; before synapse formation in the ganglia) low activities of ChAc (12 +/- 4 [mean +/- S.E.] p-mole of ACh synthesized/hr) were measured in the iris nerve terminals, indicating that ganglion cells are biochemically differentiated, immediately after cell migration is completed. The specific acitivities of ChAc and AChE rose during development and these increases were closely related to the onset and maturation of ganglionic and iris synaptic transmission. These increases in enzyme activities can be used in cholinergic synapses as an index of synapse formation. 3. The 200-fold specific increase of ChAc in iris nerve terminals which occurs at Stage 34 probably reflects an increase in synthesis of the enzyme in ganglion cells and suggests that the formation of the iris neuromuscular junction triggers the enzyme induction. It is implied that the cell responds to a signal ascending the axon from the terminal. 4. The initial increase of AChE specific activity in the ganglion occurs after transmission is established in all cells between Stage 30 and 34 and is mainly due to enzyme synthesis by the ganglion cells. In the iris there is a twofold increase in specific activity after the formation of neuromuscular junctions which probably reflects enzyme induction in the muscle subneural region. It is concluded that the specific induction of AChE in post-junctional cells is due to an influence of the prejunctional element. 5. During synaptic formation in the ciliary ganglion, reciprocal interactions between the neurones and their targets result in the induction of ChAc in the prejunctional elements and AChE in the post-junctional cells.", "contents": "Induction of cholinergic enzymes in chick ciliary ganglion and iris muscle cells during synapse formation. 1. In chick ciliary ganglia and irises, cholineacetyltransferase (ChAc) and acetylcholinesterase (AChE) activities were measured from the fifth day of incubation until 1 week after hatching. The changes in enzyme activity were correlated in time with previous electrophysiological and morphological findings of synapse formation in these tissues. 2. At Stage 26 (Hamburger & Hamilton, 1951; before synapse formation in the ganglia) low activities of ChAc (12 +/- 4 [mean +/- S.E.] p-mole of ACh synthesized/hr) were measured in the iris nerve terminals, indicating that ganglion cells are biochemically differentiated, immediately after cell migration is completed. The specific acitivities of ChAc and AChE rose during development and these increases were closely related to the onset and maturation of ganglionic and iris synaptic transmission. These increases in enzyme activities can be used in cholinergic synapses as an index of synapse formation. 3. The 200-fold specific increase of ChAc in iris nerve terminals which occurs at Stage 34 probably reflects an increase in synthesis of the enzyme in ganglion cells and suggests that the formation of the iris neuromuscular junction triggers the enzyme induction. It is implied that the cell responds to a signal ascending the axon from the terminal. 4. The initial increase of AChE specific activity in the ganglion occurs after transmission is established in all cells between Stage 30 and 34 and is mainly due to enzyme synthesis by the ganglion cells. In the iris there is a twofold increase in specific activity after the formation of neuromuscular junctions which probably reflects enzyme induction in the muscle subneural region. It is concluded that the specific induction of AChE in post-junctional cells is due to an influence of the prejunctional element. 5. During synaptic formation in the ciliary ganglion, reciprocal interactions between the neurones and their targets result in the induction of ChAc in the prejunctional elements and AChE in the post-junctional cells."} {"id": "PMID:181564", "title": "Input-output relation of transmission through cuneate nucleus.", "content": "1. In decerebrate cats, micro-electrodes were inserted into the cuneate nucleus to stimulate afferent terminals with single shocks of varying intensities. Estimates of the input and output of the nucleus were obtained by integrating antidromic responses in forelimb cutaneous nerves and orthodromic responses in the medial lemniscus. 2. Input-output curves were normally very non-linear, reflecting the high synaptic potency of small inputs. They were fitted readily by power functions, with exponents averaging 0-50. 3. The normal input-output relation rapidly disappeared after interruption of the blood supply. A loss of synaptic efficiency of small inputs was indicated by curves with exponents of greater than or equal to 1; this was associated with a sharp increase in terminal excitability. 4. Within the range of surface temperature 30-40 degrees C, warming made the input-output curves steeper but reduced terminal excitability, whereas cooling had the opposite effect. The efficiency of transmission was thus inversely correlated with terminal excitability. 5. The non-linear shape of cuneate input-output curves is probably not determined by inhibitory control, since picrotoxin depressed rather than enhanced outputs. 6. On the other hand, pentobarbitone made the input-output curves markedly steeper and tended to lower terminal excitability.", "contents": "Input-output relation of transmission through cuneate nucleus. 1. In decerebrate cats, micro-electrodes were inserted into the cuneate nucleus to stimulate afferent terminals with single shocks of varying intensities. Estimates of the input and output of the nucleus were obtained by integrating antidromic responses in forelimb cutaneous nerves and orthodromic responses in the medial lemniscus. 2. Input-output curves were normally very non-linear, reflecting the high synaptic potency of small inputs. They were fitted readily by power functions, with exponents averaging 0-50. 3. The normal input-output relation rapidly disappeared after interruption of the blood supply. A loss of synaptic efficiency of small inputs was indicated by curves with exponents of greater than or equal to 1; this was associated with a sharp increase in terminal excitability. 4. Within the range of surface temperature 30-40 degrees C, warming made the input-output curves steeper but reduced terminal excitability, whereas cooling had the opposite effect. The efficiency of transmission was thus inversely correlated with terminal excitability. 5. The non-linear shape of cuneate input-output curves is probably not determined by inhibitory control, since picrotoxin depressed rather than enhanced outputs. 6. On the other hand, pentobarbitone made the input-output curves markedly steeper and tended to lower terminal excitability."} {"id": "PMID:181565", "title": "On the elementary conductance event produced by L-glutamate and quanta of the natural transmitter at the neuromuscular junctions of Maia squinado.", "content": "1. The membrane potential of giant muscle fibres of Maia squinado was measured with an intracellular wire electrode. On applying L-glutamate to the fibre the cell deplorized and fluctuations of the membrane potential around its mean level--glutamate noise--were seen. 2. The variance of the glutamate voltage noise is proportional to the mean level of depolarization. The noise can be regarded as being caused by numerous exponentially decaying elementary voltage events about 5 X 10(-10) V in amplitude. The miniature excitatory junctional potential (min.e.j.p.) is approximately 6000 times the amplitude of the elementary voltage event produced by L-glutamate. 3. The power spectrum of glutamate voltage noise is a Lorentzian with a half-power frequency of approximately 20 Hz. 4. Min. e.j.p.s. decay exponentially with a time constant that coincides with the average lifetime of the elementary glutamate voltage event. 5. When glutamate is applied locally to a spot where extracellular min. e.j.p.s. can be recorded with a focal glass pipette, extracellular glutamate noise is seen. Glutamate noise could not be detected from elsewhere on the fibre. 6. The variance of the extracellular noise is proportional to the mean extracellular potential, and its power spectrum is a Lorentzian with a half-power frequency of about 110 Hz. 7. The extracellular min. e.j.p.s decay exponentially with a time constant that coincides with average lifetime of the elementary glutamate current event. 8. It is suggested that the decay of the quantal currents flowing at the excitatory junction is limited by the closure of the conductance channels in the post-synaptic membrane and not by the relaxation of the transmitter concentration in the synaptic cleft.", "contents": "On the elementary conductance event produced by L-glutamate and quanta of the natural transmitter at the neuromuscular junctions of Maia squinado. 1. The membrane potential of giant muscle fibres of Maia squinado was measured with an intracellular wire electrode. On applying L-glutamate to the fibre the cell deplorized and fluctuations of the membrane potential around its mean level--glutamate noise--were seen. 2. The variance of the glutamate voltage noise is proportional to the mean level of depolarization. The noise can be regarded as being caused by numerous exponentially decaying elementary voltage events about 5 X 10(-10) V in amplitude. The miniature excitatory junctional potential (min.e.j.p.) is approximately 6000 times the amplitude of the elementary voltage event produced by L-glutamate. 3. The power spectrum of glutamate voltage noise is a Lorentzian with a half-power frequency of approximately 20 Hz. 4. Min. e.j.p.s. decay exponentially with a time constant that coincides with the average lifetime of the elementary glutamate voltage event. 5. When glutamate is applied locally to a spot where extracellular min. e.j.p.s. can be recorded with a focal glass pipette, extracellular glutamate noise is seen. Glutamate noise could not be detected from elsewhere on the fibre. 6. The variance of the extracellular noise is proportional to the mean extracellular potential, and its power spectrum is a Lorentzian with a half-power frequency of about 110 Hz. 7. The extracellular min. e.j.p.s decay exponentially with a time constant that coincides with average lifetime of the elementary glutamate current event. 8. It is suggested that the decay of the quantal currents flowing at the excitatory junction is limited by the closure of the conductance channels in the post-synaptic membrane and not by the relaxation of the transmitter concentration in the synaptic cleft."} {"id": "PMID:181566", "title": "A comparison of the presynaptic and post-synaptic actions of pentobarbitone and phenobarbitone in the neuromuscular junction of the frog.", "content": "1. Pentobarbitone or phenobarbitone, in increasing concentrations up to 0-5 mM, progressively reduced the amplitude of miniature end-plate potentials (min.e.p.p.s). Pentobarbitone was the more potent of the two barbiturates in this regard. 2. Both barbiturates produced a monotonic increase in mean quantum content of the end-plate potential (e.p.p.) with increasing concentrations up to 0-5 mM. Pentobarbitone and phenobarbitone were equally potent in their action on evoked transmitter release. 3. The effect, if any, of increasing concentrations of barbiturates on the e.p.p. amplitude was depression. Therefore, over the range of concentrations examined the enhancement of transmitter release was quantitatively less than the reduction in responsiveness of the post-synaptic membrane. 4. Because of the greater ratio of post-synaptic to presynaptic actions, pentobarbitone was more potent than phenobarbitone in reducing synaptic efficacy (e.p.p. amplitude). 5. It is concluded that the presynaptic actions of pentobarbitone and phenobarbitone contribute significantly to barbiturate-induced changes in synaptic efficacy at low levels of transmitter release in the frog neuromuscular junction.", "contents": "A comparison of the presynaptic and post-synaptic actions of pentobarbitone and phenobarbitone in the neuromuscular junction of the frog. 1. Pentobarbitone or phenobarbitone, in increasing concentrations up to 0-5 mM, progressively reduced the amplitude of miniature end-plate potentials (min.e.p.p.s). Pentobarbitone was the more potent of the two barbiturates in this regard. 2. Both barbiturates produced a monotonic increase in mean quantum content of the end-plate potential (e.p.p.) with increasing concentrations up to 0-5 mM. Pentobarbitone and phenobarbitone were equally potent in their action on evoked transmitter release. 3. The effect, if any, of increasing concentrations of barbiturates on the e.p.p. amplitude was depression. Therefore, over the range of concentrations examined the enhancement of transmitter release was quantitatively less than the reduction in responsiveness of the post-synaptic membrane. 4. Because of the greater ratio of post-synaptic to presynaptic actions, pentobarbitone was more potent than phenobarbitone in reducing synaptic efficacy (e.p.p. amplitude). 5. It is concluded that the presynaptic actions of pentobarbitone and phenobarbitone contribute significantly to barbiturate-induced changes in synaptic efficacy at low levels of transmitter release in the frog neuromuscular junction."} {"id": "PMID:181575", "title": "[Stero\u00efedhormone in kleindierpraktyk (author's transl)].", "content": "The nature, origin, influence and interrelationships of the steroid hormones are reviewed. Clinical application and the treatment of feline and canine patients with these substances is discussed, with special reference to particular conditions which occur in male and female animals. The therapeutic use of corticosteroids in small animal practice are considered, and some general observations are made concerning precautions and side effects.", "contents": "[Stero\u00efedhormone in kleindierpraktyk (author's transl)]. The nature, origin, influence and interrelationships of the steroid hormones are reviewed. Clinical application and the treatment of feline and canine patients with these substances is discussed, with special reference to particular conditions which occur in male and female animals. The therapeutic use of corticosteroids in small animal practice are considered, and some general observations are made concerning precautions and side effects."} {"id": "PMID:181576", "title": "Antineoplastic and biochemical properties of arylsulfonylhydrazones of 2-formylpyridine N-oxide.", "content": "The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2-formylpyridine N-oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene, quinoline, or isoquinoline resulted in loss of activity (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N-oxide produced inactive agents (c) the pyridine N-oxide function was essential for anticancer activity, except for 4-substituted derivatives which were active without the N-oxide group, (d) replacement of the SO2 group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO2 and aryl ring with retention of anticancer potency. One of the most active members of this series, 1-oxidopyridine-2-carboxaldehyde p-toluenesulfonylhdrazone, exhibited antineoplastic activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine-3H and uridine-3H incorporation into DNA and RNA, respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound.", "contents": "Antineoplastic and biochemical properties of arylsulfonylhydrazones of 2-formylpyridine N-oxide. The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2-formylpyridine N-oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene, quinoline, or isoquinoline resulted in loss of activity (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N-oxide produced inactive agents (c) the pyridine N-oxide function was essential for anticancer activity, except for 4-substituted derivatives which were active without the N-oxide group, (d) replacement of the SO2 group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO2 and aryl ring with retention of anticancer potency. One of the most active members of this series, 1-oxidopyridine-2-carboxaldehyde p-toluenesulfonylhdrazone, exhibited antineoplastic activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine-3H and uridine-3H incorporation into DNA and RNA, respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound."} {"id": "PMID:181577", "title": "Synthesis of new cyclic nucleotides and their differential stimulatory effects on thyroid function in mice.", "content": "Various 8-substituted cAMP analogues were converted into the corresponding N6,O2'-dibutyryl, N6-monobutyryl, or O2'-monobutyryl derivatives and the parent compounds as well as the new derivatives were tested for TSH-like stimulation of the thyroid function in mice in vivo by means of the McKenzie bioassay. It was found that a pronounced stimulatory effect on the thyroid secretion can be produced by certain cyclic nucleotides. The most potent compounds, 8H2N-cAMP, 8MeS-cAMP, and 8N3-cAMP at 15-30 mg/kg iv, showed an activity approximately one order of magnitude higher than that of cAMP and comparable to the action of 0.6-1.0 mU of TSH per mouse iv. Radioimmunological determination of thyroxine levels in the serum confirmed these results. Serum T4 levels in mice injected, for instance, with 8MeS-cAMP (30 mg/kg) rose from 4.85 +/- 0.25 to 6.32 +/- 0.41 mug/100 ml in 1 h, the net increase in T4 being comparable to that produced by TSH (1 mU/mouse) under identical experimental conditions. Introduction of one or two butyryl groups (in the N6 and/or O2' position) significantly increased or decreased the biological activity, dependent on the parent compound, but no direct correlation between biological activity and degree of butyrylation was apparent. The effect of these compounds on the thyroid seems to be specific for cyclic nucleotides because 8MeS-5'AMP which resembles 8MeS-cAMP but lacks the cyclic phosphate structure is inactive in the McKenzie bioassay and in the T4 radioimmunoassay.", "contents": "Synthesis of new cyclic nucleotides and their differential stimulatory effects on thyroid function in mice. Various 8-substituted cAMP analogues were converted into the corresponding N6,O2'-dibutyryl, N6-monobutyryl, or O2'-monobutyryl derivatives and the parent compounds as well as the new derivatives were tested for TSH-like stimulation of the thyroid function in mice in vivo by means of the McKenzie bioassay. It was found that a pronounced stimulatory effect on the thyroid secretion can be produced by certain cyclic nucleotides. The most potent compounds, 8H2N-cAMP, 8MeS-cAMP, and 8N3-cAMP at 15-30 mg/kg iv, showed an activity approximately one order of magnitude higher than that of cAMP and comparable to the action of 0.6-1.0 mU of TSH per mouse iv. Radioimmunological determination of thyroxine levels in the serum confirmed these results. Serum T4 levels in mice injected, for instance, with 8MeS-cAMP (30 mg/kg) rose from 4.85 +/- 0.25 to 6.32 +/- 0.41 mug/100 ml in 1 h, the net increase in T4 being comparable to that produced by TSH (1 mU/mouse) under identical experimental conditions. Introduction of one or two butyryl groups (in the N6 and/or O2' position) significantly increased or decreased the biological activity, dependent on the parent compound, but no direct correlation between biological activity and degree of butyrylation was apparent. The effect of these compounds on the thyroid seems to be specific for cyclic nucleotides because 8MeS-5'AMP which resembles 8MeS-cAMP but lacks the cyclic phosphate structure is inactive in the McKenzie bioassay and in the T4 radioimmunoassay."} {"id": "PMID:181578", "title": "Synthesis and biological activities of 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine and 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine.", "content": "5-Trifluoromethyl-2'-deoxyuridine (1) was tosylated with p-toluenesulfonyl chloride in dry pyridine at 3 degrees to give 5-trifluoromethyl-5'-O-(p-tolylsulfonyl)-2'-deoxyuridine (2), which was converted to 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine (3) by reacting with lithium azide in N,N-dimethylformamide at 85-90 degrees for 2 h. Compound 3 was then hydrogenated in ethanol-water (1:1, v/v) at room temperature and 35 psi of hydrogen pressure, using 10% palladium on charcoal as cstalyst, to yield 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine (4). Compound 4 is about fourfold less potent than compound 1 as an antiviral agent but is about 40-fold less toxic to the host Vero cells. Thus the therapeutic index of compound 1 has been improved by a factor of 10 by replacement of the 5'-hydroxyl with an amino group. Compound 1, however, is more than 100-fold more inhibitory to Sarcoma 180 cells in culture relative to compound 4. Compound 3 is markedly less potent than compound 1 or 4 as either an antiviral or an antineoplastic compound.", "contents": "Synthesis and biological activities of 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine and 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine. 5-Trifluoromethyl-2'-deoxyuridine (1) was tosylated with p-toluenesulfonyl chloride in dry pyridine at 3 degrees to give 5-trifluoromethyl-5'-O-(p-tolylsulfonyl)-2'-deoxyuridine (2), which was converted to 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine (3) by reacting with lithium azide in N,N-dimethylformamide at 85-90 degrees for 2 h. Compound 3 was then hydrogenated in ethanol-water (1:1, v/v) at room temperature and 35 psi of hydrogen pressure, using 10% palladium on charcoal as cstalyst, to yield 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine (4). Compound 4 is about fourfold less potent than compound 1 as an antiviral agent but is about 40-fold less toxic to the host Vero cells. Thus the therapeutic index of compound 1 has been improved by a factor of 10 by replacement of the 5'-hydroxyl with an amino group. Compound 1, however, is more than 100-fold more inhibitory to Sarcoma 180 cells in culture relative to compound 4. Compound 3 is markedly less potent than compound 1 or 4 as either an antiviral or an antineoplastic compound."} {"id": "PMID:181579", "title": "Lanthanum and some other cation-induced changes in fluidity of synaptosomal membrane studied with nitroxide stearate spin labels.", "content": "Using nitroxide fatty acid spin labels, the effects of some cations such as La3+, Cd2+ and Hg2+ on synaptosomal membranes were studied by observing changes in their ESR spectra. The labels were incorporated almost instantaneously into synaptosomes isolated from rat brain cortex. ESR spectra of the spin-labeled synaptosomes were significantly braodened immediately upon adding La3+, Ce3+, Cd2+ or Hg2+ but hardly affected by Ca2+, Sr2+ and Ba2+. The magnitude of the change in the separation of the outer two peaks in ESR spectra (2T') depends on the number (n) of methylene units between the polar head group and the spin-label (nitroxide) group; that is, it increases with decreasing n. Among these ions, the effect of La3+ was the greatest and appeared to be in parallel with the amount of La3+ bound with the synaptosomes. On the other hand, K+, Rb+ or Li+ causes hardly any significant changes.", "contents": "Lanthanum and some other cation-induced changes in fluidity of synaptosomal membrane studied with nitroxide stearate spin labels. Using nitroxide fatty acid spin labels, the effects of some cations such as La3+, Cd2+ and Hg2+ on synaptosomal membranes were studied by observing changes in their ESR spectra. The labels were incorporated almost instantaneously into synaptosomes isolated from rat brain cortex. ESR spectra of the spin-labeled synaptosomes were significantly braodened immediately upon adding La3+, Ce3+, Cd2+ or Hg2+ but hardly affected by Ca2+, Sr2+ and Ba2+. The magnitude of the change in the separation of the outer two peaks in ESR spectra (2T') depends on the number (n) of methylene units between the polar head group and the spin-label (nitroxide) group; that is, it increases with decreasing n. Among these ions, the effect of La3+ was the greatest and appeared to be in parallel with the amount of La3+ bound with the synaptosomes. On the other hand, K+, Rb+ or Li+ causes hardly any significant changes."} {"id": "PMID:181580", "title": "Ion transport by rabbit colon. I. Active and passive components.", "content": "Descending rabbit colon, stripped of muscularis externa, absorbs Na and Cl under short-circuit conditions and exhibits a residual ion flux, consistent with HCO3 secretion, whose magnitude is approximately equal to the rate of active Cl absorption. Net K transport was not observed under short-circuit conditions. The results of ion replacement studies and of treatment with ouabain or amiloride suggest that the short-circuit current ISC is determined solely by the rate of active Na transport and that the net movements of Cl and HCO3 are mediated by a Na-independent, electrically-neutral, anion exchange process. Cyclic AMP stimulates an electrogenic Cl secretion, abolishes HCO3 secretion but does not affect the rate of Na absorption under short-circuit conditions. Studies of the effect of transepithelial potential difference on the serosa-to-mucosa fluxes Jism of Na, K and Cl suggest that JNasm,JIsm and one-third of JCl-sm may be attributed to ionic diffusion. The permeabilities of the passive conductance pathway(s) are such that Pk:PNa:PCl= 1.0:0.07:0.11. Electrolyte transport by in vitro rabbit colon closely resembles that reported from in vivo studies of mammalian colon and thus may serve as a useful model for the further study of colonic ion transport mechanisms.", "contents": "Ion transport by rabbit colon. I. Active and passive components. Descending rabbit colon, stripped of muscularis externa, absorbs Na and Cl under short-circuit conditions and exhibits a residual ion flux, consistent with HCO3 secretion, whose magnitude is approximately equal to the rate of active Cl absorption. Net K transport was not observed under short-circuit conditions. The results of ion replacement studies and of treatment with ouabain or amiloride suggest that the short-circuit current ISC is determined solely by the rate of active Na transport and that the net movements of Cl and HCO3 are mediated by a Na-independent, electrically-neutral, anion exchange process. Cyclic AMP stimulates an electrogenic Cl secretion, abolishes HCO3 secretion but does not affect the rate of Na absorption under short-circuit conditions. Studies of the effect of transepithelial potential difference on the serosa-to-mucosa fluxes Jism of Na, K and Cl suggest that JNasm,JIsm and one-third of JCl-sm may be attributed to ionic diffusion. The permeabilities of the passive conductance pathway(s) are such that Pk:PNa:PCl= 1.0:0.07:0.11. Electrolyte transport by in vitro rabbit colon closely resembles that reported from in vivo studies of mammalian colon and thus may serve as a useful model for the further study of colonic ion transport mechanisms."} {"id": "PMID:181584", "title": "The molecular evolution of cytochrome c in eukaryotes.", "content": "Using many more cytochrome sequences than previously available, we have confirmed: 1, the eukaryotic cytochrome c diverged from a common ancestor; 2, the ancestral eukaryotic cytochrome c was not greatly different in character from those present today; 3, fixations are non-randomly distributed among the codons, there being evidence for at least four classes of variability; 4, there are similar classes of variability when the data are considered according to the nucleotide position within the codon; 5, the number of covarions (concomitantly variable codons) in mammalian cytochrome c genes is about 12 and the same value has been obtained for dicotyledenous plants as well; 6, all of the hyper- and most highly variable codons are for external residues, nearly 60 per cent of the invariable codons are for internal residues and nearly half of the codons for internal residues are invariable; 7, the first nucleotide position of a codon is more likely and the second position less likely to fix mutations than would be expected on the basis of the number of ways that alternative amino acids can be reached; 8, the character of nucleotide replacements is enormously non-random, with G-A interchanges representing 42% of those observed in the first nucleotide position, but the observation does not stem from a bias in the DNA strand receiving the mutation, nor from the presence of a compositional equilibrium, nor from a bias in the frequency with which different nucleotides mutate, but rather from a bias in the acceptability of an alternative nucleotide as circumscribed by the functional acceptability of the new amino acid encoded; and 9, the unit evolutionary period is approximately 150 million years/observable (amino acid changing) nucleotide replacement/cytochrome c covarion in two diverging lines. Wherever non-randomness has been observed, it has always been consistent with the consideration that an alternative amino acid at any location is more likely to be acceptable the more closely it resembles the present amino acid in its physico-chemical properties. Finally, in no case did the a priori assumption of a biologically realistic phylogeny lead to any observations or conclusions that were in any way significantly different from those obtained when the phylogeny was based solely upon the sequences, proving that the earlier results were not a consequence of some internal circularity.", "contents": "The molecular evolution of cytochrome c in eukaryotes. Using many more cytochrome sequences than previously available, we have confirmed: 1, the eukaryotic cytochrome c diverged from a common ancestor; 2, the ancestral eukaryotic cytochrome c was not greatly different in character from those present today; 3, fixations are non-randomly distributed among the codons, there being evidence for at least four classes of variability; 4, there are similar classes of variability when the data are considered according to the nucleotide position within the codon; 5, the number of covarions (concomitantly variable codons) in mammalian cytochrome c genes is about 12 and the same value has been obtained for dicotyledenous plants as well; 6, all of the hyper- and most highly variable codons are for external residues, nearly 60 per cent of the invariable codons are for internal residues and nearly half of the codons for internal residues are invariable; 7, the first nucleotide position of a codon is more likely and the second position less likely to fix mutations than would be expected on the basis of the number of ways that alternative amino acids can be reached; 8, the character of nucleotide replacements is enormously non-random, with G-A interchanges representing 42% of those observed in the first nucleotide position, but the observation does not stem from a bias in the DNA strand receiving the mutation, nor from the presence of a compositional equilibrium, nor from a bias in the frequency with which different nucleotides mutate, but rather from a bias in the acceptability of an alternative nucleotide as circumscribed by the functional acceptability of the new amino acid encoded; and 9, the unit evolutionary period is approximately 150 million years/observable (amino acid changing) nucleotide replacement/cytochrome c covarion in two diverging lines. Wherever non-randomness has been observed, it has always been consistent with the consideration that an alternative amino acid at any location is more likely to be acceptable the more closely it resembles the present amino acid in its physico-chemical properties. Finally, in no case did the a priori assumption of a biologically realistic phylogeny lead to any observations or conclusions that were in any way significantly different from those obtained when the phylogeny was based solely upon the sequences, proving that the earlier results were not a consequence of some internal circularity."} {"id": "PMID:181585", "title": "Molecular evolution as a process of message refinement.", "content": "Amino acid sequences are often said to code for proteins. Taking that statement literally, we propose a methodology in which protein sequences appear as messages and as such are amenable to the techniques of signal analysis. Not only does this view of amino acid sequences as messages appear to be tenable, but the clarity of expression of these sequences seems to increase, i.e., the noisiness decreases, consonant with notions of ascendancy in the hierarchy of morphological taxonomy.", "contents": "Molecular evolution as a process of message refinement. Amino acid sequences are often said to code for proteins. Taking that statement literally, we propose a methodology in which protein sequences appear as messages and as such are amenable to the techniques of signal analysis. Not only does this view of amino acid sequences as messages appear to be tenable, but the clarity of expression of these sequences seems to increase, i.e., the noisiness decreases, consonant with notions of ascendancy in the hierarchy of morphological taxonomy."} {"id": "PMID:181586", "title": "A vestibulothalamic pathway: electrophysiological demonstration in the cat by localized cooling.", "content": "Localized cooling was used in the search for vestibulothalamic pathways and a study was made of its effect on the activity of the thalamic neurons brought into action by stimulation of the vestibular nerve. Two cell populations were identified by their distinctive latencies in the ventral part of the posterior thalamus. Short latency responses were transmitted monosynaptically by means of a direct controlateral pathway whose course was identified. For long latency responses, the hypothesis of a polysynaptic path seems probable.", "contents": "A vestibulothalamic pathway: electrophysiological demonstration in the cat by localized cooling. Localized cooling was used in the search for vestibulothalamic pathways and a study was made of its effect on the activity of the thalamic neurons brought into action by stimulation of the vestibular nerve. Two cell populations were identified by their distinctive latencies in the ventral part of the posterior thalamus. Short latency responses were transmitted monosynaptically by means of a direct controlateral pathway whose course was identified. For long latency responses, the hypothesis of a polysynaptic path seems probable."} {"id": "PMID:181590", "title": "Temperature-sensitive mutants of vesicular stomatitis virus are conditionally defective particles that interfere with and are rescued by wild-type virus.", "content": "Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups I, II and IV inhibited the replication of wild-type vesicular stomatitis virus when mixed infections were carried out in BHK21 cells at 32, 37, and 39.5 C. The group IV mutant (ts G 41) was most effective in this regard; wild-type virus yields were inhibited almost 1,000-fold in mixed infections with this mutant at 32 C. In the case of group I and II mutants, inhibition of wild-type virus replication at 37 and 39.5 C was accompanied by an enhancement (up to 15,000-fold) of the yields of the coinfecting ts mutant. The yields of the group IV mutant (ts G 41) were not enhanced by mixed infections with wild-type virus at any temperature, although this mutant inhibited wild-type virus replication at all temperatures. The dominance of the replication of ts mutants at 37 C provides a rationale for the selection and maintenance of ts virus in persistently infected cells.", "contents": "Temperature-sensitive mutants of vesicular stomatitis virus are conditionally defective particles that interfere with and are rescued by wild-type virus. Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups I, II and IV inhibited the replication of wild-type vesicular stomatitis virus when mixed infections were carried out in BHK21 cells at 32, 37, and 39.5 C. The group IV mutant (ts G 41) was most effective in this regard; wild-type virus yields were inhibited almost 1,000-fold in mixed infections with this mutant at 32 C. In the case of group I and II mutants, inhibition of wild-type virus replication at 37 and 39.5 C was accompanied by an enhancement (up to 15,000-fold) of the yields of the coinfecting ts mutant. The yields of the group IV mutant (ts G 41) were not enhanced by mixed infections with wild-type virus at any temperature, although this mutant inhibited wild-type virus replication at all temperatures. The dominance of the replication of ts mutants at 37 C provides a rationale for the selection and maintenance of ts virus in persistently infected cells."} {"id": "PMID:181591", "title": "Synthesis of type C virus particles from murine-cultured cells induced by iododeoxyuridine. V. Effect of interferon and its interaction with dexamethasone.", "content": "Previous studies have shown that in certain cell systems dexamethasone may enhance the production of type C viruses. Conversely, interferon has been shown to inhibit their production. Both appear to exert their influence late in the viral replication cycle rather than on the synthesis of viral-specific RNA. In this report dexamethasone and interferon have been used to study some aspects of the mechanisms involved in the synthesis of type C viruses in murine K-BALB cells following induction of virus production by iododeoxyuridine. Interferon inhibited production of xenotropic type C virus induced by iododeoxyuridine from K-BALB cells both in the absence and presence of dexamethasone, but it did not affect production of N-tropic type C virus. Exposure of the cells to interferon for longer than 12 h was required for maximum effect. Two types of inhibitory effects were observed: one diminished by dexamethasone when the steroid was added 24 h after interferon removal, and the second resistant to dexamethasone. The concentration of intracellular group-specific antigen was diminshed after interferon and increased after dexamethasone exposure. When induced cells were treated with both interferon and dexamethasone, the intracellular group-specific protein concentration was slightly increased, but virus production was reduced 10-fold compared with induced cells treated with dexamethasone alone. We conclude that interferon and dexamethasone may affect both the synthesis of viral proteins and the assembly or release of virus particles and that dexamethasone can partially nullify the inhibitory activity of interferon. The results also support previous conclusions that the regulatory mechanisms for synthesis of viral proteins and for the release of viral particles may differ and that controls for xenotropic and ecotropic virus formation may not be identical.", "contents": "Synthesis of type C virus particles from murine-cultured cells induced by iododeoxyuridine. V. Effect of interferon and its interaction with dexamethasone. Previous studies have shown that in certain cell systems dexamethasone may enhance the production of type C viruses. Conversely, interferon has been shown to inhibit their production. Both appear to exert their influence late in the viral replication cycle rather than on the synthesis of viral-specific RNA. In this report dexamethasone and interferon have been used to study some aspects of the mechanisms involved in the synthesis of type C viruses in murine K-BALB cells following induction of virus production by iododeoxyuridine. Interferon inhibited production of xenotropic type C virus induced by iododeoxyuridine from K-BALB cells both in the absence and presence of dexamethasone, but it did not affect production of N-tropic type C virus. Exposure of the cells to interferon for longer than 12 h was required for maximum effect. Two types of inhibitory effects were observed: one diminished by dexamethasone when the steroid was added 24 h after interferon removal, and the second resistant to dexamethasone. The concentration of intracellular group-specific antigen was diminshed after interferon and increased after dexamethasone exposure. When induced cells were treated with both interferon and dexamethasone, the intracellular group-specific protein concentration was slightly increased, but virus production was reduced 10-fold compared with induced cells treated with dexamethasone alone. We conclude that interferon and dexamethasone may affect both the synthesis of viral proteins and the assembly or release of virus particles and that dexamethasone can partially nullify the inhibitory activity of interferon. The results also support previous conclusions that the regulatory mechanisms for synthesis of viral proteins and for the release of viral particles may differ and that controls for xenotropic and ecotropic virus formation may not be identical."} {"id": "PMID:181592", "title": "Amphotropic host range of naturally occuring wild mouse leukemia viruses.", "content": "Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely separated areas in southern California show an unusually wide in vitro host range. They replicate well in human, feline, canine, guinea pig, rabbit, rat, and mouse cells, whereas bovine, hamster, and avian cells are resistant. Since this host range includes that of both mouse tropic (ecotropic) and xenotropic murine leukemia viruses, they are designated as \"amphotropic\". No purely xenotropic virus component is detectable in these field isolates. They may represent the \"wild\" or ancestral viruses from which the ecotropic and xenotrophic murine leukemia virus strains of laboratory mice have been derived.", "contents": "Amphotropic host range of naturally occuring wild mouse leukemia viruses. Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely separated areas in southern California show an unusually wide in vitro host range. They replicate well in human, feline, canine, guinea pig, rabbit, rat, and mouse cells, whereas bovine, hamster, and avian cells are resistant. Since this host range includes that of both mouse tropic (ecotropic) and xenotropic murine leukemia viruses, they are designated as \"amphotropic\". No purely xenotropic virus component is detectable in these field isolates. They may represent the \"wild\" or ancestral viruses from which the ecotropic and xenotrophic murine leukemia virus strains of laboratory mice have been derived."} {"id": "PMID:181593", "title": "Structure of Herpesvirus saimiri genomes: arrangement of heavy and light sequences in the M genome.", "content": "Herpesvirus saimiri contains two species of DNA molecules. (i) The M genome is composed of 70% light (L) DNA (36% cytosine plus guanine; density in CsCl, 1.695 g/ml), which consists of unique sequences, and 30% heavy (H) DNA (71% cytosine plus guanine; density, 1.729 g/ml). (ii) The H genome contains heavy sequences exclusively. H sequences in M and H genomes cross-hybridize completely and are cleaved identically by restriction endonuclease R-Sma I into four classes of fragments with molecular weights of about 360,000, 300,000, 130,000 and 40,000, respectively. H sequences are chains of identical repeat units in tandem arrangement. The molecular weight of each repeat unit is about 830,000. L sequences have no cleavage site for endo R-Sma I H sequences are terminally arranged at both ends of the M genome, as seen by electron microscopy after partial denaturation. The length of the individual heavy ends varies between 21 mum and less than 1 mum, whereas the light region is uniform in size (35.3+/-0.35 mum). As a rule, molecules with a long heavy end at one side have a short heavy end at the other side, thus giving rise to a limited size heterogeneity. Orientation of M DNA molecules by the denaturation map of the light region shows that the longer heavy end may be located at the left or at the right side of the M genome.", "contents": "Structure of Herpesvirus saimiri genomes: arrangement of heavy and light sequences in the M genome. Herpesvirus saimiri contains two species of DNA molecules. (i) The M genome is composed of 70% light (L) DNA (36% cytosine plus guanine; density in CsCl, 1.695 g/ml), which consists of unique sequences, and 30% heavy (H) DNA (71% cytosine plus guanine; density, 1.729 g/ml). (ii) The H genome contains heavy sequences exclusively. H sequences in M and H genomes cross-hybridize completely and are cleaved identically by restriction endonuclease R-Sma I into four classes of fragments with molecular weights of about 360,000, 300,000, 130,000 and 40,000, respectively. H sequences are chains of identical repeat units in tandem arrangement. The molecular weight of each repeat unit is about 830,000. L sequences have no cleavage site for endo R-Sma I H sequences are terminally arranged at both ends of the M genome, as seen by electron microscopy after partial denaturation. The length of the individual heavy ends varies between 21 mum and less than 1 mum, whereas the light region is uniform in size (35.3+/-0.35 mum). As a rule, molecules with a long heavy end at one side have a short heavy end at the other side, thus giving rise to a limited size heterogeneity. Orientation of M DNA molecules by the denaturation map of the light region shows that the longer heavy end may be located at the left or at the right side of the M genome."} {"id": "PMID:181594", "title": "Mechanisms of infection with Epstein-Barr virus. I. Viral DNA replication and formation of noninfectious virus particles in superinfected Raji cells.", "content": "Human lymphoblastoid Raji cells, which do not produce virus, supported replication of Epstein-Barr virus (EBV) upon superinfection. Early antigen, viral capsid antigen, and virions were produced in Raji cells superinfected with EBV. Viral DNA replicated under complete inhibition of host cell DNA synthesis to the extent that a few micrograms of EBV DNA were recovered from 107 superinfected Raji cells, corresponding to 5,000 viral genomes/cell. Homology of the synthesized viral DNA to parental EBV DNA was more than 90%. Virions produced by the Raji cells contained a 55S DNA but failed to induce early antigen, viral capsid antigen, and viral DNA synthesis after a second superinfection of Raji cells.", "contents": "Mechanisms of infection with Epstein-Barr virus. I. Viral DNA replication and formation of noninfectious virus particles in superinfected Raji cells. Human lymphoblastoid Raji cells, which do not produce virus, supported replication of Epstein-Barr virus (EBV) upon superinfection. Early antigen, viral capsid antigen, and virions were produced in Raji cells superinfected with EBV. Viral DNA replicated under complete inhibition of host cell DNA synthesis to the extent that a few micrograms of EBV DNA were recovered from 107 superinfected Raji cells, corresponding to 5,000 viral genomes/cell. Homology of the synthesized viral DNA to parental EBV DNA was more than 90%. Virions produced by the Raji cells contained a 55S DNA but failed to induce early antigen, viral capsid antigen, and viral DNA synthesis after a second superinfection of Raji cells."} {"id": "PMID:181595", "title": "Cytomegalovirus proteins. I. Polypeptides of virions and dense bodies.", "content": "Cytomegalovirus virions and dense bodies were purified by sucrose velocity and equilibrium centrifugation from the medium of fibroblasts infected with the strain AD169. The final virus preparations were purified more than 228-fold with respect to cellular proteins as determined by double-isotopic labeling and at least 1,600-fold on the basis of changes in the ratio of total protein to virus particles. The protein content of purified particles approximated that found for purified preparations of other herpesviruses. Twenty polypeptides ranging from 22,000 to greater than 230,000 molecular weight were detected in purified virus preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Polypeptides of virions and dense bodies were allocated on the basis of analyses of preparations containing differing percentages of virions and dense bodies. Six polypeptides were represented predominantly or exclusively in virions, and four polypeptides were represented predominantly or exclusively in dense bodies, whereas the remainder appeared to be shared by both types of particles. Four polypeptides were glycosylated, and at least three of these appeared to be shared by both particles. Four polypeptides were glycosylated, and at least three of these appeared to be shared by both particle types. The protein composition of cytomegalovirus differs profoundly from that of herpes simplex virus.", "contents": "Cytomegalovirus proteins. I. Polypeptides of virions and dense bodies. Cytomegalovirus virions and dense bodies were purified by sucrose velocity and equilibrium centrifugation from the medium of fibroblasts infected with the strain AD169. The final virus preparations were purified more than 228-fold with respect to cellular proteins as determined by double-isotopic labeling and at least 1,600-fold on the basis of changes in the ratio of total protein to virus particles. The protein content of purified particles approximated that found for purified preparations of other herpesviruses. Twenty polypeptides ranging from 22,000 to greater than 230,000 molecular weight were detected in purified virus preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Polypeptides of virions and dense bodies were allocated on the basis of analyses of preparations containing differing percentages of virions and dense bodies. Six polypeptides were represented predominantly or exclusively in virions, and four polypeptides were represented predominantly or exclusively in dense bodies, whereas the remainder appeared to be shared by both types of particles. Four polypeptides were glycosylated, and at least three of these appeared to be shared by both particles. Four polypeptides were glycosylated, and at least three of these appeared to be shared by both particle types. The protein composition of cytomegalovirus differs profoundly from that of herpes simplex virus."} {"id": "PMID:181596", "title": "Effect of trypsin on mouse mammary tumor virus.", "content": "Undisrupted mouse mammary tumor virus (MuMTV) derived from the milk of of RIII mice has been analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron microscopy after treatment with insolubilized trypsin. No alterations were found in viral fine structure by either freeze-etch or negative-stain electron microscopy. No alterations were found in the ability of trypsinized virus to compete in a radioimmune assay for viral antigens. Infectivity experiments indicate no significant differences in the ability of treated virus to infect C57Bl mice. However, significant differences were observed in polypeptide composition. The intensely periodic acid-Schiff-positive band, gp140, was shown by galactose oxidase-borotritide labeling to be degraded into a fragment of 125,000 molecular weight. The major glycoprotein, gp55, was split into fragments of 36,000 and 23,000 molecular weight, both of which stained with periodic acid-Schiff stain. Gp68 was removed from the virus. Experiments with purified, iodinated gp55 showed that the trypsin-induced fragments of gp55 were immunologically active. We conclude that: (i) certain glycoproteins at the surface of MuMTV are accessible to an insoluble form of trypsin, (ii) the trypsin causes a nick in the polypeptide chain without affecting the configuration of the molecule; (iii) the nicked molecules remain bound to the virus; and (iv) the presence of these nicked molecules does not interfere with the biological or antigenic expression of virus function.", "contents": "Effect of trypsin on mouse mammary tumor virus. Undisrupted mouse mammary tumor virus (MuMTV) derived from the milk of of RIII mice has been analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron microscopy after treatment with insolubilized trypsin. No alterations were found in viral fine structure by either freeze-etch or negative-stain electron microscopy. No alterations were found in the ability of trypsinized virus to compete in a radioimmune assay for viral antigens. Infectivity experiments indicate no significant differences in the ability of treated virus to infect C57Bl mice. However, significant differences were observed in polypeptide composition. The intensely periodic acid-Schiff-positive band, gp140, was shown by galactose oxidase-borotritide labeling to be degraded into a fragment of 125,000 molecular weight. The major glycoprotein, gp55, was split into fragments of 36,000 and 23,000 molecular weight, both of which stained with periodic acid-Schiff stain. Gp68 was removed from the virus. Experiments with purified, iodinated gp55 showed that the trypsin-induced fragments of gp55 were immunologically active. We conclude that: (i) certain glycoproteins at the surface of MuMTV are accessible to an insoluble form of trypsin, (ii) the trypsin causes a nick in the polypeptide chain without affecting the configuration of the molecule; (iii) the nicked molecules remain bound to the virus; and (iv) the presence of these nicked molecules does not interfere with the biological or antigenic expression of virus function."} {"id": "PMID:181597", "title": "Comparative membrane microviscosity of fish and mammalian rhabdoviruses studied by fluorescence depolarization.", "content": "The microviscosity of the hydrophobic region of the membrane of infectious hematopoietic necrosis virus was determined using fluorescence depolarization analysis of the probe 1,6-diphenyl-1,3,5-hexatriene and was found to be much lower at 37 C than that of another rhabdovirus, vesicular stomatitis virus. However, the microviscosity of this fish virus at 18 C, the temperature at which it was grown, corresponded to the microviscosity of vesicular stomatitis virus at 37 C. Data obtained with the fish virus host cell (chinook salmon embryo cells) grown at 18 C suggest that its membranes have a lower microviscosity than either L-929 or BHK-21 cells (the vesicular stomatitis virus host cells) grown at 37 C.", "contents": "Comparative membrane microviscosity of fish and mammalian rhabdoviruses studied by fluorescence depolarization. The microviscosity of the hydrophobic region of the membrane of infectious hematopoietic necrosis virus was determined using fluorescence depolarization analysis of the probe 1,6-diphenyl-1,3,5-hexatriene and was found to be much lower at 37 C than that of another rhabdovirus, vesicular stomatitis virus. However, the microviscosity of this fish virus at 18 C, the temperature at which it was grown, corresponded to the microviscosity of vesicular stomatitis virus at 37 C. Data obtained with the fish virus host cell (chinook salmon embryo cells) grown at 18 C suggest that its membranes have a lower microviscosity than either L-929 or BHK-21 cells (the vesicular stomatitis virus host cells) grown at 37 C."} {"id": "PMID:181598", "title": "Excision of viral DNA from host cell DNA after induction of simian virus 40-transformed hamster cells.", "content": "Simian virus 40-transformed hamster cells were induced to produce infectious virus by treatment with mitomycin C or gamma-irradiation. A portion of the simian virus-40 DNA, which is integrated into the host cell genome in uninduced cells, was recovered in a pool of relatively low-molecular-weight DNA early after induction treatment in the absence of DNA replication. The data indicte that excision of the viral genome occurs subsequent to the induction stimulus.", "contents": "Excision of viral DNA from host cell DNA after induction of simian virus 40-transformed hamster cells. Simian virus 40-transformed hamster cells were induced to produce infectious virus by treatment with mitomycin C or gamma-irradiation. A portion of the simian virus-40 DNA, which is integrated into the host cell genome in uninduced cells, was recovered in a pool of relatively low-molecular-weight DNA early after induction treatment in the absence of DNA replication. The data indicte that excision of the viral genome occurs subsequent to the induction stimulus."} {"id": "PMID:181599", "title": "Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus.", "content": "Noncytocidal persistent infections at 37 C of mouse L cells (Lvsv) with infective B particles of vesicular stomatitis virus (VSV) could be established only in the presence of large numbers of defective interfering (DI) particles. Under these conditions, there was a rapid spontaneous selection of temperature-sensitive (ts) virus. At 10 days there was an increase to 17.8% in the frequency of ts clones in the virus population; by 17 days this frequency had reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5 C, the nonpermissive temperature used. All 34 of the clones isolated from the 84-day fluid had an RNA-phenotype, and 8 clones that were tested all belonged to VSV complementation group I. When tested by an interference assay, Lvsv fluids did not contain significant numbers of DI particles (less than 1 DI/PFU). Furthermore, persistent infection of L cells at 37 C could be initiated under conditions in which few, if any, DI particles were present by using low input multiplicities (10(-4) and 10(-5) of a clonal isolate of an RNA-group I mutant obtained from Lvsv cells. On the basis of these and other results, a mechanism is proposed to explain the role of ts mutants in both the establishment and maintenance of the persistently infected state.", "contents": "Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus. Noncytocidal persistent infections at 37 C of mouse L cells (Lvsv) with infective B particles of vesicular stomatitis virus (VSV) could be established only in the presence of large numbers of defective interfering (DI) particles. Under these conditions, there was a rapid spontaneous selection of temperature-sensitive (ts) virus. At 10 days there was an increase to 17.8% in the frequency of ts clones in the virus population; by 17 days this frequency had reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5 C, the nonpermissive temperature used. All 34 of the clones isolated from the 84-day fluid had an RNA-phenotype, and 8 clones that were tested all belonged to VSV complementation group I. When tested by an interference assay, Lvsv fluids did not contain significant numbers of DI particles (less than 1 DI/PFU). Furthermore, persistent infection of L cells at 37 C could be initiated under conditions in which few, if any, DI particles were present by using low input multiplicities (10(-4) and 10(-5) of a clonal isolate of an RNA-group I mutant obtained from Lvsv cells. On the basis of these and other results, a mechanism is proposed to explain the role of ts mutants in both the establishment and maintenance of the persistently infected state."} {"id": "PMID:181600", "title": "Neoplasia at the site of ureterosigmoidostomy.", "content": "An increased incidence of neoplasia at the site of ureterosigmoidostomy must be considered in patients being evaluated for or who have undergone this procedure. A case of mucinous adenocarcinoma 24 years following bilateral ureterosigmoidostomy is reported. This patient had bilateral hydroureteronephrosis, which led to left nephroureterectomy and right cutaneous ureterostomy. Mucinous adenocarcinoma was diagnosed only after the edematous, protruding and inflamed cutaneous ureterostomy stoma was biopsied. To our knowledge this is the first reported case of transfer of such a malignancy to the skin at the time of cutaneous ureterostomy. We recommend that ureterosigmoidostomy be performed only in patients with a limited life expectancy who agree to long-term followup. This followup should be frequent, complete and continue for the remainder of the patient's life. We consider the tendency for development of neoplasia at the ureterosigmoid anastomosis to be a relative contraindication to ureterosigmoidostomy. However, with proper patient selection and followup, ureterosigmoidostomy is still a remarkably satisfactory method of urinary diversion.", "contents": "Neoplasia at the site of ureterosigmoidostomy. An increased incidence of neoplasia at the site of ureterosigmoidostomy must be considered in patients being evaluated for or who have undergone this procedure. A case of mucinous adenocarcinoma 24 years following bilateral ureterosigmoidostomy is reported. This patient had bilateral hydroureteronephrosis, which led to left nephroureterectomy and right cutaneous ureterostomy. Mucinous adenocarcinoma was diagnosed only after the edematous, protruding and inflamed cutaneous ureterostomy stoma was biopsied. To our knowledge this is the first reported case of transfer of such a malignancy to the skin at the time of cutaneous ureterostomy. We recommend that ureterosigmoidostomy be performed only in patients with a limited life expectancy who agree to long-term followup. This followup should be frequent, complete and continue for the remainder of the patient's life. We consider the tendency for development of neoplasia at the ureterosigmoid anastomosis to be a relative contraindication to ureterosigmoidostomy. However, with proper patient selection and followup, ureterosigmoidostomy is still a remarkably satisfactory method of urinary diversion."} {"id": "PMID:181601", "title": "The absorption of antibiotics from the bladder.", "content": "The movement across the bladder epithelium of polymyxin B, bacitracin and neomycin is investigated in the human during postoperative irrigation. No appreciable amounts of these antibiotics enter the systemic circulation by this route.", "contents": "The absorption of antibiotics from the bladder. The movement across the bladder epithelium of polymyxin B, bacitracin and neomycin is investigated in the human during postoperative irrigation. No appreciable amounts of these antibiotics enter the systemic circulation by this route."} {"id": "PMID:181602", "title": "Respiratory syncytial virus and heart disease. A report of two cases.", "content": "Two patients had cardiac disease and serological evidence for respiratory syncytial virus (RSV) infection. The first patient had myocarditis and complete atrioventricular heart block with repeated syncopal episodes two weeks following infection. The second patient had alcoholic cardiomyopathy and worsening congestive heart failure associated with RSV infection. The significance of RSV infection in these two patients may bear a significant relationship to sudden infant death syndrome, chronic cardiomyopathy, and alcohol-related heart disease. Cardiac disease secondary to RSV infection may be more prevalent than is presently recognized.", "contents": "Respiratory syncytial virus and heart disease. A report of two cases. Two patients had cardiac disease and serological evidence for respiratory syncytial virus (RSV) infection. The first patient had myocarditis and complete atrioventricular heart block with repeated syncopal episodes two weeks following infection. The second patient had alcoholic cardiomyopathy and worsening congestive heart failure associated with RSV infection. The significance of RSV infection in these two patients may bear a significant relationship to sudden infant death syndrome, chronic cardiomyopathy, and alcohol-related heart disease. Cardiac disease secondary to RSV infection may be more prevalent than is presently recognized."} {"id": "PMID:181606", "title": "Recurrent conjugal neuralgia caused by Herpesvirus hominis type 2.", "content": "Leg neuralgia is usually caused by nerve root irritation, and is seldom considered of viral origin. Two married couples had recurrent leg pain in a dermatome distribution. In each episode, after one to three days of neuralgia, herpetic vesicles appear on or near the genitalia. Herpesvirus hominis (HVH) was isolated from vesicles or cervix in three patients and was serologically identified as herpesvirus honinis type 2. Prolonged follow-up has not shown progression of the syndrome or any permanent neurologic damage. Treatment with topical neutral red and photoinactivation has not only reduced local lesion healing time and frequency of attacks, but it has also given prompt relief of neuralgia.", "contents": "Recurrent conjugal neuralgia caused by Herpesvirus hominis type 2. Leg neuralgia is usually caused by nerve root irritation, and is seldom considered of viral origin. Two married couples had recurrent leg pain in a dermatome distribution. In each episode, after one to three days of neuralgia, herpetic vesicles appear on or near the genitalia. Herpesvirus hominis (HVH) was isolated from vesicles or cervix in three patients and was serologically identified as herpesvirus honinis type 2. Prolonged follow-up has not shown progression of the syndrome or any permanent neurologic damage. Treatment with topical neutral red and photoinactivation has not only reduced local lesion healing time and frequency of attacks, but it has also given prompt relief of neuralgia."} {"id": "PMID:181608", "title": "True and false left anterior hemiblock: vectorcardiographic study.", "content": "For confirming the configuration of the QRS loop in left anterior hemiblock, 82 cases with the frontal QRS vector above minus 30 degrees were collected and classified by the configuration of the horizontal QRS loop. Thereafter, a comparison has been made between the configuration of the QRS loop in clinical cases and that in the authors' construction method, and the following findings for criteria of left anterior hemiblock are obtained. 1) The afferent limb of the frontal QRS loop is dislocated to the left and more superiorly. 2) The efferent and afferent limbs of the horizontal QRS loop are located left posteriorly. The configuration of the horizontal QRS loop is long and narrow and the direction of inscription is clockwise, a figure of 8 or counterclockwise. 3) Cases with the right posterosuperior dislocation of the afferent limb of the QRS loop is excluded from left anterior hemiblock.", "contents": "True and false left anterior hemiblock: vectorcardiographic study. For confirming the configuration of the QRS loop in left anterior hemiblock, 82 cases with the frontal QRS vector above minus 30 degrees were collected and classified by the configuration of the horizontal QRS loop. Thereafter, a comparison has been made between the configuration of the QRS loop in clinical cases and that in the authors' construction method, and the following findings for criteria of left anterior hemiblock are obtained. 1) The afferent limb of the frontal QRS loop is dislocated to the left and more superiorly. 2) The efferent and afferent limbs of the horizontal QRS loop are located left posteriorly. The configuration of the horizontal QRS loop is long and narrow and the direction of inscription is clockwise, a figure of 8 or counterclockwise. 3) Cases with the right posterosuperior dislocation of the afferent limb of the QRS loop is excluded from left anterior hemiblock."} {"id": "PMID:181621", "title": "Induction of antiviral activity in vivo and in vitro by human placenta ribonucleic acid treated with nitrous acid.", "content": "Induction of antiviral activity and interferon by human placenta ribonucleic acid deaminated with sodium nitrite (NO2-RNA) was studied in vitro and in vitro. (1) Viral multiplication in diploid cells from human kidney (HK cells) was depressed by pretreatment with NO2-RNA, but not by pre-treatment with the original placenta RNA. (2) NO2-RNA showed an interferon-inducing activity in rabbits and mice. (3) NO2-RNA sedimenting in 18 S and 28 S regions showed a higher antiviral activity than that sedimenting in 4 S region.", "contents": "Induction of antiviral activity in vivo and in vitro by human placenta ribonucleic acid treated with nitrous acid. Induction of antiviral activity and interferon by human placenta ribonucleic acid deaminated with sodium nitrite (NO2-RNA) was studied in vitro and in vitro. (1) Viral multiplication in diploid cells from human kidney (HK cells) was depressed by pretreatment with NO2-RNA, but not by pre-treatment with the original placenta RNA. (2) NO2-RNA showed an interferon-inducing activity in rabbits and mice. (3) NO2-RNA sedimenting in 18 S and 28 S regions showed a higher antiviral activity than that sedimenting in 4 S region."} {"id": "PMID:181623", "title": "Further studies of the action of cyclic AMP on the electrical and mechanical activities of intestinal smooth muscle.", "content": "Effects of externally applied cyclic AMP and other adrenergic stimulants on the electrical and mechanical activities of the cat small intestine were observed by using pressure electrodes. The electrical and mechanical activities were suppressed by cyclic AMP and beta-stimulants. Those inhibitory actions of cyclic AMP and beta-stimulants were potentiated under the treatment with caffeine, theophylline and papaverine which inhibits the phosphodiesterase activity. On the other hand, the inhibitory action of cyclic AMP and beta-stimulants was decreased in imidazole, an agent that increases phosphodiesterase activity. Exogenous applied concanavalin A, an agent that inhibits the adenyl cyclase activity, showed no observable changes in both activities but the effects of beta-stimulants were decreased after treatment with concanavalin A. No obvious changes on both activities were obtained in cyclic GMP and dibutyryl cyclic GMP. These findings tentatively support the hypothesis that cyclic AMP is a second messenger in the inhibitory responses to beta-stimulants on the intestinal smooth muscle. However, it is also concluded that the inhibition of mechanical activity caused by cyclic AMP is partially due to suppression of the membrane activity.", "contents": "Further studies of the action of cyclic AMP on the electrical and mechanical activities of intestinal smooth muscle. Effects of externally applied cyclic AMP and other adrenergic stimulants on the electrical and mechanical activities of the cat small intestine were observed by using pressure electrodes. The electrical and mechanical activities were suppressed by cyclic AMP and beta-stimulants. Those inhibitory actions of cyclic AMP and beta-stimulants were potentiated under the treatment with caffeine, theophylline and papaverine which inhibits the phosphodiesterase activity. On the other hand, the inhibitory action of cyclic AMP and beta-stimulants was decreased in imidazole, an agent that increases phosphodiesterase activity. Exogenous applied concanavalin A, an agent that inhibits the adenyl cyclase activity, showed no observable changes in both activities but the effects of beta-stimulants were decreased after treatment with concanavalin A. No obvious changes on both activities were obtained in cyclic GMP and dibutyryl cyclic GMP. These findings tentatively support the hypothesis that cyclic AMP is a second messenger in the inhibitory responses to beta-stimulants on the intestinal smooth muscle. However, it is also concluded that the inhibition of mechanical activity caused by cyclic AMP is partially due to suppression of the membrane activity."} {"id": "PMID:181629", "title": "[Experimental aortic stenosis, its subsequent correction and the activity of oxidative enzymes in the myocardium].", "content": "The activity of the respiratory enzymes of myocardial mitochondria--succinatedehydrogenase and cytochromixidase--was studied in experimentally induced aortic stenosis and after its elimination in 98 mongrel dogs. The observation period of stenosis was 1, 15, 30 and 60 days, and after its elimination--1, 7, 15 and 30 days. The activity of the enzymes in question was found to grow after the production of aortic stenosis. The highest level of their enzymatic activity was observed on the 15th day after the induction of stenosis. By the 30th and 60th day the enzymatic activity underwent some decrease, although it persisted on a level above the initial. The activity of succinatedehydrogenase fell sharper. After the elimination of the stenosis the activity of both enzymes decreased, and by the 7th day it was below the initial level. By the 15th day after the removal of the ligature from the aorta the activity of both enzymes corresponded to the initial values and did not change further till the end of the 1st month. The dynamics of the activity of succinatedehydrogenase and cytochromixidase after an experimentally induced aortic stenosis and its subsequent elimination seems to depend on the nature of the changes in the function of the heart muscle performed under such experimental pathology, and on the degree of coronary flow enhancement.", "contents": "[Experimental aortic stenosis, its subsequent correction and the activity of oxidative enzymes in the myocardium]. The activity of the respiratory enzymes of myocardial mitochondria--succinatedehydrogenase and cytochromixidase--was studied in experimentally induced aortic stenosis and after its elimination in 98 mongrel dogs. The observation period of stenosis was 1, 15, 30 and 60 days, and after its elimination--1, 7, 15 and 30 days. The activity of the enzymes in question was found to grow after the production of aortic stenosis. The highest level of their enzymatic activity was observed on the 15th day after the induction of stenosis. By the 30th and 60th day the enzymatic activity underwent some decrease, although it persisted on a level above the initial. The activity of succinatedehydrogenase fell sharper. After the elimination of the stenosis the activity of both enzymes decreased, and by the 7th day it was below the initial level. By the 15th day after the removal of the ligature from the aorta the activity of both enzymes corresponded to the initial values and did not change further till the end of the 1st month. The dynamics of the activity of succinatedehydrogenase and cytochromixidase after an experimentally induced aortic stenosis and its subsequent elimination seems to depend on the nature of the changes in the function of the heart muscle performed under such experimental pathology, and on the degree of coronary flow enhancement."} {"id": "PMID:181632", "title": "Morphology of the ascending thick limb of Henle.", "content": "The morphologic characteristics of the medullary and cortical segments of the ascending thick limb of Henle were examined in the rat utilizing light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The kidneys of six normal female Sprague-Dawley rats were preserved for morphological examination utilizing in vivo intravascular perfusion with 6.25% glutaraldehyde buffered in 0.1m sodium cacodylate. SEM revealed the presence of two distinctly different patterns of surface structure among the population of cells forming the epithelium of the ascending thick limb, a roughsurfaced cell with prominent microvilli (R cell) and a smoothsurfaced cell generally devoid of extensive microvilli except along the lateral cell margins (S cell). This variation in surface structure was confirmed with light microscopy and TEM. Throughout both the medullary and cortical segments of the ascending thick limb, the R cells possessed extensive lateral processes radiating form the main cell body to interdigitate with adjacent cells. Lateral processes of S cells were less common than those of the R cells in the inner stripe of the outer medulla, but increased in number and complexity in the outer stripe of the outer medulla and throughout the cortex. S cells outnumbered R cells in the inner stripe of the outer medulla. As the thick limb transversed the outer medulla and ascended toward the parent renal corpuscle, there was a marked increase in the relative number of R cells. In the cortical segment of the ascending thick limb, both the R and S cells tended to acquire a more extensive population of microvilli over their luminal surface making it increasingly difficult to establish clearcut distinctions between the two surface patterns. With the possible exception that vesicles and tubulovesicular profiles located in the apical region were more numerous in many of the S cells, additional morphological differences between the rough and smoothsurfaced cells were not evident. Whether the morphological results represent two distinct cell types or simply a variation in the structure of a single cell type, their presence must be considered in future structural-functional studies involving the ascending thick limb of Henle in the rat.", "contents": "Morphology of the ascending thick limb of Henle. The morphologic characteristics of the medullary and cortical segments of the ascending thick limb of Henle were examined in the rat utilizing light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The kidneys of six normal female Sprague-Dawley rats were preserved for morphological examination utilizing in vivo intravascular perfusion with 6.25% glutaraldehyde buffered in 0.1m sodium cacodylate. SEM revealed the presence of two distinctly different patterns of surface structure among the population of cells forming the epithelium of the ascending thick limb, a roughsurfaced cell with prominent microvilli (R cell) and a smoothsurfaced cell generally devoid of extensive microvilli except along the lateral cell margins (S cell). This variation in surface structure was confirmed with light microscopy and TEM. Throughout both the medullary and cortical segments of the ascending thick limb, the R cells possessed extensive lateral processes radiating form the main cell body to interdigitate with adjacent cells. Lateral processes of S cells were less common than those of the R cells in the inner stripe of the outer medulla, but increased in number and complexity in the outer stripe of the outer medulla and throughout the cortex. S cells outnumbered R cells in the inner stripe of the outer medulla. As the thick limb transversed the outer medulla and ascended toward the parent renal corpuscle, there was a marked increase in the relative number of R cells. In the cortical segment of the ascending thick limb, both the R and S cells tended to acquire a more extensive population of microvilli over their luminal surface making it increasingly difficult to establish clearcut distinctions between the two surface patterns. With the possible exception that vesicles and tubulovesicular profiles located in the apical region were more numerous in many of the S cells, additional morphological differences between the rough and smoothsurfaced cells were not evident. Whether the morphological results represent two distinct cell types or simply a variation in the structure of a single cell type, their presence must be considered in future structural-functional studies involving the ascending thick limb of Henle in the rat."} {"id": "PMID:181634", "title": "The glomerular mesangium: uptake and transport of intravenously injected colloidal carbon in rats.", "content": "Collodial carbon, 70 mg/100 g, was injected into rats which were sacificed for histologic study of the kidneys at intervals of five minutes to seven weeks. Transient thrombocytopenia and albuminuria were observed. Uptake of carbon by the mesangium of glomeruli was maximal at 32 hr and gradually decreased thereafter. Semiquantitative analysis of the distribution of carbon particles within glomeruli revealed a predominately peripheral localization during early time periods, and increased relative concentration of particles within more central zones and in the lacis area at the vascular pole of the glomerulus at two to seven weeks, indicating that one of the mechanisms for clearance of materials from the mesangium was movement of particles in the direction of the lacis area. Sequential electron microscopic studies showed that carbon particles moved through fenestrae in the endothelium covering the mesangium into channels between mesangial cells. Observations at later intervals suggested that carbon eventually reached the vascular pole by being passed on from one mesangial cell to the next. Vasoactive amines or other substances derived from platelets may play an important role in initiating the process of mesangial uptake.", "contents": "The glomerular mesangium: uptake and transport of intravenously injected colloidal carbon in rats. Collodial carbon, 70 mg/100 g, was injected into rats which were sacificed for histologic study of the kidneys at intervals of five minutes to seven weeks. Transient thrombocytopenia and albuminuria were observed. Uptake of carbon by the mesangium of glomeruli was maximal at 32 hr and gradually decreased thereafter. Semiquantitative analysis of the distribution of carbon particles within glomeruli revealed a predominately peripheral localization during early time periods, and increased relative concentration of particles within more central zones and in the lacis area at the vascular pole of the glomerulus at two to seven weeks, indicating that one of the mechanisms for clearance of materials from the mesangium was movement of particles in the direction of the lacis area. Sequential electron microscopic studies showed that carbon particles moved through fenestrae in the endothelium covering the mesangium into channels between mesangial cells. Observations at later intervals suggested that carbon eventually reached the vascular pole by being passed on from one mesangial cell to the next. Vasoactive amines or other substances derived from platelets may play an important role in initiating the process of mesangial uptake."} {"id": "PMID:181637", "title": "[Immunological cell surface markers in infectious mononucleosis (author's transl)].", "content": "Using a direct immunofluorescence technique and a spontaneous rosette formation with sheep red blood cells it could be demonstrated that the large mononuclear cells in infectious mononucleosis consisted mainly of T-lymphocytes. It is likely that infectious mononucleosis represents a primary B-lymphcoyte infection with the Epstein-Barr virus like in the Burkitt lymphoma. In contrast to this malignant lymphoma, interaction in infectious mononucleosis leads to a secondary T-lymphocyte proliferation.", "contents": "[Immunological cell surface markers in infectious mononucleosis (author's transl)]. Using a direct immunofluorescence technique and a spontaneous rosette formation with sheep red blood cells it could be demonstrated that the large mononuclear cells in infectious mononucleosis consisted mainly of T-lymphocytes. It is likely that infectious mononucleosis represents a primary B-lymphcoyte infection with the Epstein-Barr virus like in the Burkitt lymphoma. In contrast to this malignant lymphoma, interaction in infectious mononucleosis leads to a secondary T-lymphocyte proliferation."} {"id": "PMID:181638", "title": "Hypophosphatasia: a cytochemical study of phosphatase activities.", "content": "Skeletal abnormalities with defective formation of mature calcified bone are the most prominent clinical features of hypophosphatasia. Low concentrations of serum and tissue alkaline phosphatase and elevated plasma and urinary levels of phosphorylethanolamine (PEA) are also present. Although PEA is hydrolyzed by serum alkaline phosphatase, the relationship between PEA and the deficiency is unclear. PEA has not previously been tested as a cytochemical substrate for the in situ demonstration of human alkaline phosphatase activity. We have studied alkaline phosphatase activity in hypophosphatasia in tissue sections, utilizing PEA and adenosinetriphosphate (ATP) as well as the usual beta-glycerophosphate and naphthol phosphate substrates. Neutral and acid phosphatase activities were also examined. Our results demonstrate that PEA is a substrate for the localization of alkaline phosphatase in normal human tissue, but is not hydrolyzed in hypophosphatasia in the liver, brain or costochondral junction under alkaline conditions. In the kidney in hypophosphatasia only the straight segments of proximal tubules that rim the medullary rays are reactive with PEA. Similar results in hypophosphatasia were obtained at an alkaline pH with ATP, beta-glycerophosphate, and naphthol phosphate. However, the defect in hypophosphatasia is not a generalized deficiency of membrane-associated phosphatases because membranes that were deficient in alkaline phosphatase activity demonstrated normal reactivity with ATP at neutral pH. In addition, thiamine pyrophosphate was also split by Golgi membranes within the cytoplasm. Acid hydrolysis of beta-glycerophosphate by lysosomes was normal.", "contents": "Hypophosphatasia: a cytochemical study of phosphatase activities. Skeletal abnormalities with defective formation of mature calcified bone are the most prominent clinical features of hypophosphatasia. Low concentrations of serum and tissue alkaline phosphatase and elevated plasma and urinary levels of phosphorylethanolamine (PEA) are also present. Although PEA is hydrolyzed by serum alkaline phosphatase, the relationship between PEA and the deficiency is unclear. PEA has not previously been tested as a cytochemical substrate for the in situ demonstration of human alkaline phosphatase activity. We have studied alkaline phosphatase activity in hypophosphatasia in tissue sections, utilizing PEA and adenosinetriphosphate (ATP) as well as the usual beta-glycerophosphate and naphthol phosphate substrates. Neutral and acid phosphatase activities were also examined. Our results demonstrate that PEA is a substrate for the localization of alkaline phosphatase in normal human tissue, but is not hydrolyzed in hypophosphatasia in the liver, brain or costochondral junction under alkaline conditions. In the kidney in hypophosphatasia only the straight segments of proximal tubules that rim the medullary rays are reactive with PEA. Similar results in hypophosphatasia were obtained at an alkaline pH with ATP, beta-glycerophosphate, and naphthol phosphate. However, the defect in hypophosphatasia is not a generalized deficiency of membrane-associated phosphatases because membranes that were deficient in alkaline phosphatase activity demonstrated normal reactivity with ATP at neutral pH. In addition, thiamine pyrophosphate was also split by Golgi membranes within the cytoplasm. Acid hydrolysis of beta-glycerophosphate by lysosomes was normal."} {"id": "PMID:181639", "title": "Isolated lamellar bodies from rat lung: correlated ultrastructural and biochemical studies.", "content": "Lamellar bodies isolated from rat lung homogenates were prepared for electron microscopy by two methods: OsO4 fixation followed by dehydration either with acetone or ethanol. Electron microscopy revealed that the acetone-dehydrated fraction contained many well preserved lamellar bodies with intact outer membrane, and the high retention of a material of low electron density between the fine and closely spaced concentric lamellae. This appearance was contrasted by the increased loss of this interlamellar material and coarse and irregularly spaced lamellae in the ethanol-dehydrated fraction. The supernatants from each respective fixation and dehydration were collected for lipid and protein analyses in an attempt to correlate any detected biochemical difference with a correspondingly modified ultrastructural appearance. Thin layer chromatography on the supernatant from the ethanol-dehydrated fraction revealed the extraction of 40 per cent lecithin and 4 per cent phosphatidylglycerol as compared to 1 per cent lecithin and an undeterminably small percentage of phosphatidylglycerol extracted by acetone dehydration. The effect of fixation and dehydration upon the extraction of chemical components of the lamellar bodies was compared to extraction by those of the following treatments: (1) freezing and thawing (a loss of 7 per cent lecithin, undetectably small losses of phosphatidylglycerol and protein); (2) incubation at 37 degrees C. with magnetic stirring (losses of 35 per cent lecithin, 5 per cent phosphatidylglycerol, and 4 percent protein, respectively); (3) sonication (loss of 57 per cent lecithin, 31 per cent phosphatidylglycerol, and 27 per cent protein, respectively). Further lipid analyses of the supernatants from dehydration and those obtained from the mechanical treatments revealed dipalmitoyl lecithin as the most readily extracted lipid. These data indicate that OsO4 fixation followed by acetone dehydration improves the preservation of the lamellar body ultrastructure by retaining an amorphous material between the lamellae, thus preserving the spatial relationship between the lamellae, and further that this improved morphologic preservation correlates well with retention of disaturated lecithin.", "contents": "Isolated lamellar bodies from rat lung: correlated ultrastructural and biochemical studies. Lamellar bodies isolated from rat lung homogenates were prepared for electron microscopy by two methods: OsO4 fixation followed by dehydration either with acetone or ethanol. Electron microscopy revealed that the acetone-dehydrated fraction contained many well preserved lamellar bodies with intact outer membrane, and the high retention of a material of low electron density between the fine and closely spaced concentric lamellae. This appearance was contrasted by the increased loss of this interlamellar material and coarse and irregularly spaced lamellae in the ethanol-dehydrated fraction. The supernatants from each respective fixation and dehydration were collected for lipid and protein analyses in an attempt to correlate any detected biochemical difference with a correspondingly modified ultrastructural appearance. Thin layer chromatography on the supernatant from the ethanol-dehydrated fraction revealed the extraction of 40 per cent lecithin and 4 per cent phosphatidylglycerol as compared to 1 per cent lecithin and an undeterminably small percentage of phosphatidylglycerol extracted by acetone dehydration. The effect of fixation and dehydration upon the extraction of chemical components of the lamellar bodies was compared to extraction by those of the following treatments: (1) freezing and thawing (a loss of 7 per cent lecithin, undetectably small losses of phosphatidylglycerol and protein); (2) incubation at 37 degrees C. with magnetic stirring (losses of 35 per cent lecithin, 5 per cent phosphatidylglycerol, and 4 percent protein, respectively); (3) sonication (loss of 57 per cent lecithin, 31 per cent phosphatidylglycerol, and 27 per cent protein, respectively). Further lipid analyses of the supernatants from dehydration and those obtained from the mechanical treatments revealed dipalmitoyl lecithin as the most readily extracted lipid. These data indicate that OsO4 fixation followed by acetone dehydration improves the preservation of the lamellar body ultrastructure by retaining an amorphous material between the lamellae, thus preserving the spatial relationship between the lamellae, and further that this improved morphologic preservation correlates well with retention of disaturated lecithin."} {"id": "PMID:181643", "title": "Biosynthesis of collagen and its alterations in pathological states.", "content": "The biosynthesis of collagen involves a number of unique post-translational modifications which are catalyzed by many specific enzymes. The main steps in collagen biosynthesis are transcription and translation, hydroxylations of prolyl and lysyl residues, glycosylations of hydroxylysyl residues, chain association and disulphide bonding, triple helix formation, secretion of procollagen into the extracellular matrix, conversion of procollagen into collagen, specific aggregation of collagen molecules and crosslink formation. Information about these modifications has rapidly increased during recent years, and initial information is available about the regulation and possibilities of specific pharmacological control of collagen biosynthesis at the level of these stages. Elucidation of the biochemical defect in an inborn error of collagen biosynthesis in man was reported for the first time in 1972 and subsequently several additional defects have been characterized. Alterations in collagen biosynthesis are also found during growth and ageing, as well as in many acquired pathological states: data about the nature of such changes in now rapidly accumulating.", "contents": "Biosynthesis of collagen and its alterations in pathological states. The biosynthesis of collagen involves a number of unique post-translational modifications which are catalyzed by many specific enzymes. The main steps in collagen biosynthesis are transcription and translation, hydroxylations of prolyl and lysyl residues, glycosylations of hydroxylysyl residues, chain association and disulphide bonding, triple helix formation, secretion of procollagen into the extracellular matrix, conversion of procollagen into collagen, specific aggregation of collagen molecules and crosslink formation. Information about these modifications has rapidly increased during recent years, and initial information is available about the regulation and possibilities of specific pharmacological control of collagen biosynthesis at the level of these stages. Elucidation of the biochemical defect in an inborn error of collagen biosynthesis in man was reported for the first time in 1972 and subsequently several additional defects have been characterized. Alterations in collagen biosynthesis are also found during growth and ageing, as well as in many acquired pathological states: data about the nature of such changes in now rapidly accumulating."} {"id": "PMID:181645", "title": "Seeking a social disposition for the medical patient: CAAST, a simple and objective clinical index.", "content": "An index for the rapid and simple identification on admission of patients at high risk of becoming disposition problems was developed based on the patient's status of Continence, Ambulation, Age, Social Background, and Thought Processes (CAAST). One hundred seven consecutive admissions to City Hospital Center at Elmhurst were evaluated on admission according to the CAAST index and followed until discharge. The time that the patients remained in the hospital after their medical problems had been cared for was defined as social stay and was correlated with CAAST score. The high CAAST groups were found to have significantly increased mortality and longer average social stays with almost 40 per cent of their in-hospital time spent awaiting disposition. A high CAAST score should alert the physician to seek earlier help from social service in achieving a more rapid and more appropriate disposition for his or her patient.", "contents": "Seeking a social disposition for the medical patient: CAAST, a simple and objective clinical index. An index for the rapid and simple identification on admission of patients at high risk of becoming disposition problems was developed based on the patient's status of Continence, Ambulation, Age, Social Background, and Thought Processes (CAAST). One hundred seven consecutive admissions to City Hospital Center at Elmhurst were evaluated on admission according to the CAAST index and followed until discharge. The time that the patients remained in the hospital after their medical problems had been cared for was defined as social stay and was correlated with CAAST score. The high CAAST groups were found to have significantly increased mortality and longer average social stays with almost 40 per cent of their in-hospital time spent awaiting disposition. A high CAAST score should alert the physician to seek earlier help from social service in achieving a more rapid and more appropriate disposition for his or her patient."} {"id": "PMID:181647", "title": "Hemolytic anemias. Failure of the red cell membrane.", "content": "The normal erythrocyte membrane is composed of nearly equivalent amounts of lipid and protein. The lipid portion of the membrane has been well studied. Even though de novo synthesis of lipid does not occur in human red cells, many biochemical pathways exist which facilitate detoxification of lipid breakdown products and lipid renewal. Rare defects in these processes are associated with hemolytic disorders. Recent studies have revealed that the membrane proteins are diverse and suggest that protein dysfunction may also account for clinical disease. Protein and lipid are entwined in a physicochemical relationship which is probably best depicted by the classic lipid bilayer with interspersed proteins in both the inner and outer surfaces and also spanning the bilayer. Membrane failure results in hemolytic anemia. This failure can be intrinsic, caused by abnormal lipid or protein constituents; or extrinsic, with a normal membrane being unable to counteract physical, chemical or immunologic stress. Clinical examples of membrane failure and hemolytic anemia can be separated into three groups according to the predominant mechanism of the hemolysis: fragmentation, whole-cell lysis, and filtration and entrapment. Although these mechanisms can act separately or in concert, the final hemolytic destruction of the cell can usually be traced to a failure of membrane function.", "contents": "Hemolytic anemias. Failure of the red cell membrane. The normal erythrocyte membrane is composed of nearly equivalent amounts of lipid and protein. The lipid portion of the membrane has been well studied. Even though de novo synthesis of lipid does not occur in human red cells, many biochemical pathways exist which facilitate detoxification of lipid breakdown products and lipid renewal. Rare defects in these processes are associated with hemolytic disorders. Recent studies have revealed that the membrane proteins are diverse and suggest that protein dysfunction may also account for clinical disease. Protein and lipid are entwined in a physicochemical relationship which is probably best depicted by the classic lipid bilayer with interspersed proteins in both the inner and outer surfaces and also spanning the bilayer. Membrane failure results in hemolytic anemia. This failure can be intrinsic, caused by abnormal lipid or protein constituents; or extrinsic, with a normal membrane being unable to counteract physical, chemical or immunologic stress. Clinical examples of membrane failure and hemolytic anemia can be separated into three groups according to the predominant mechanism of the hemolysis: fragmentation, whole-cell lysis, and filtration and entrapment. Although these mechanisms can act separately or in concert, the final hemolytic destruction of the cell can usually be traced to a failure of membrane function."} {"id": "PMID:181648", "title": "[Single congenital granular cell myoblastoma (congenital epulis) of the gum].", "content": "A case of granular-cells (congenital epulis type) in the gum in a female newborn is reported. The differential characteristics between this tumor and the \"so-called granular cell myoblastoma\" are described.", "contents": "[Single congenital granular cell myoblastoma (congenital epulis) of the gum]. A case of granular-cells (congenital epulis type) in the gum in a female newborn is reported. The differential characteristics between this tumor and the \"so-called granular cell myoblastoma\" are described."} {"id": "PMID:181649", "title": "Detection of ototoxicity from drugs applied topically to the middle ear space.", "content": "This paper summarizes data obtained from two separate studies done in our laboratory. Both studies were done to investigate the possibility that drugs commonly applied to the middle ear space could be the cause of sensori-neural hearing loss. The two drugs that were felt to be the most likely candidates for the studies were neomycin and polymyxin B. In the neomycin study, the various drug concentrations were administered three times a day for four weeks. In the polymyxin B study, the administration was three times a day for two weeks. Cochlear function was evaluated electrophysiologically and by examination of surface preparations of the organ Corti. The data show that both neomycin and polymyxin B can, in concentrations similar to those found in commercially available otic drops, induce cochlear damage when they are applied to the middle ear space of guinea pigs. The degree of damage produced is related. In the case of neomycin, it was shown that the effect worsens as the duration of the dosage administration is extended...", "contents": "Detection of ototoxicity from drugs applied topically to the middle ear space. This paper summarizes data obtained from two separate studies done in our laboratory. Both studies were done to investigate the possibility that drugs commonly applied to the middle ear space could be the cause of sensori-neural hearing loss. The two drugs that were felt to be the most likely candidates for the studies were neomycin and polymyxin B. In the neomycin study, the various drug concentrations were administered three times a day for four weeks. In the polymyxin B study, the administration was three times a day for two weeks. Cochlear function was evaluated electrophysiologically and by examination of surface preparations of the organ Corti. The data show that both neomycin and polymyxin B can, in concentrations similar to those found in commercially available otic drops, induce cochlear damage when they are applied to the middle ear space of guinea pigs. The degree of damage produced is related. In the case of neomycin, it was shown that the effect worsens as the duration of the dosage administration is extended..."} {"id": "PMID:181650", "title": "A critical analysis of current trends in the management of Bell's palsy.", "content": "The treatment of Bell's palsy has been a controversial subject for many years. During the past 10 years 152 papers pertaining to this affection of the facial nerve have apperaed in the American literature. Ninety-seven of these were general discussions of the etiology, pathology, prognosis and treatment of this condition: 20 were concerned with ascertaining the status of the facial nerve by electrical tests and four with the activity of the chorda tympani nerve in patients with Bell's palsy. The remaining 31 articles specifically discussed the treatment of Bell's palsy. As a result of this obvious interest in Bell's palsy, one would expect that the treatment of this affection of the facial nerve would be more or less uniform at this time. This is not the case, however, for the literature demonstrates it to be in a state of flux. Although steroid therapy has replaced other regimens of medical therapy to a large extent, surgical intervention still has its proponents. It is interesting to note that at the time of this review of the literature, no report of a controlled, double-blind study of the efficacy of steroid therapy for Bell's palsy has appeared in the American literature.", "contents": "A critical analysis of current trends in the management of Bell's palsy. The treatment of Bell's palsy has been a controversial subject for many years. During the past 10 years 152 papers pertaining to this affection of the facial nerve have apperaed in the American literature. Ninety-seven of these were general discussions of the etiology, pathology, prognosis and treatment of this condition: 20 were concerned with ascertaining the status of the facial nerve by electrical tests and four with the activity of the chorda tympani nerve in patients with Bell's palsy. The remaining 31 articles specifically discussed the treatment of Bell's palsy. As a result of this obvious interest in Bell's palsy, one would expect that the treatment of this affection of the facial nerve would be more or less uniform at this time. This is not the case, however, for the literature demonstrates it to be in a state of flux. Although steroid therapy has replaced other regimens of medical therapy to a large extent, surgical intervention still has its proponents. It is interesting to note that at the time of this review of the literature, no report of a controlled, double-blind study of the efficacy of steroid therapy for Bell's palsy has appeared in the American literature."} {"id": "PMID:181656", "title": "Effects of sex on formation and properties of plasma very low density lipoprotein in vivo.", "content": "The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of male animals. Following injection with Triton WR-1339, the concentration of VLDL lipids was higher in female rats (triacylglycerol) or similar (phospholipid, cholesterol, and cholesteryl esters) in both sexes. Female rats secreted much more VLDL traicylglycerol into the plasma compartment than did the male animals under the same experimental conditions. No differences were observed in lipid composition of the VLDL or in the position of the VLDL in the zonal rotor after ultracentrifugation in a density gradient of the lipoprotein from plasma of normal male and female rats before treatment with the detergent. However, after treatment with Triton, a higher proportion of the VLDL particles isolated from plasma of female rats displayed a more rapid rate-zonal flotation in the ultracentrifuge than did the VLDL produced by the male. The VLDL secreted by female rats contained fewer moles of phospholipid and free sterol per mol triacylglycerol than did the VLDL secreted by male animals under identical experimental conditions. The molar ratio of free cholesterol:cholesteryl ester in the VLDL secreted after treatment with Trition increased in both male and female rats. Simultaneously, the content of arachidonic acid in phospholipid of VLDL increased with a concomitant decrease in cholesteryl ester. These changes in fatty acid composition suggest that the inhibitory effect of Triton on lecithin-cholesterol acyl transferase activity affects the exchange of lipids between VLDL and high density lipoprotein. It can be concluded from the data reported here that sex influences the concentration of plasma lipids in vivo and the output and properties of the VLDL.", "contents": "Effects of sex on formation and properties of plasma very low density lipoprotein in vivo. The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of male animals. Following injection with Triton WR-1339, the concentration of VLDL lipids was higher in female rats (triacylglycerol) or similar (phospholipid, cholesterol, and cholesteryl esters) in both sexes. Female rats secreted much more VLDL traicylglycerol into the plasma compartment than did the male animals under the same experimental conditions. No differences were observed in lipid composition of the VLDL or in the position of the VLDL in the zonal rotor after ultracentrifugation in a density gradient of the lipoprotein from plasma of normal male and female rats before treatment with the detergent. However, after treatment with Triton, a higher proportion of the VLDL particles isolated from plasma of female rats displayed a more rapid rate-zonal flotation in the ultracentrifuge than did the VLDL produced by the male. The VLDL secreted by female rats contained fewer moles of phospholipid and free sterol per mol triacylglycerol than did the VLDL secreted by male animals under identical experimental conditions. The molar ratio of free cholesterol:cholesteryl ester in the VLDL secreted after treatment with Trition increased in both male and female rats. Simultaneously, the content of arachidonic acid in phospholipid of VLDL increased with a concomitant decrease in cholesteryl ester. These changes in fatty acid composition suggest that the inhibitory effect of Triton on lecithin-cholesterol acyl transferase activity affects the exchange of lipids between VLDL and high density lipoprotein. It can be concluded from the data reported here that sex influences the concentration of plasma lipids in vivo and the output and properties of the VLDL."} {"id": "PMID:181657", "title": "Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia).", "content": "Chylomicron \"remnants\" are formed by the selective removal of triglyceride catalyzed by lipoprotein lipase. To investigate a possible defect in the clearance of these remnants in the pathophysiology of broad-beta disease (type III hyperlipoproteinemia), subjects with this disorder and comparison subjects with endogenous hypertriglyceridemia (and type IV lipoprotein patterns) ingested an oral fat load (corn oil: cocoa butter, 1:1, 50 g/sq M) containing retinyl ester, 100 mg, with or without 15 muCi 15-(14) C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf more than 400) and very low density lipoproteins (VLDS, Sf20-400) over the ensuing 24-72 hr. Vitamin A was chosen as a marker for exogenous sterol assimilation since, like cholesterol, it is absorbed in the small intestine and cosecreted in esterified form with triglyceride in the chylomicron core; however, unlike cholesterol, once having been removed by the liver, it cannot be recycled inot VLDL, but subsequently circulates only as a complex with the high density retinol binding protein. Thus measurements of the vitamin A/triglyceride ratio in Sf greater than 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins. These studies confirmed the intital concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf greater than 20 vitamin A in VLDL 24 hr after its ingestion. The vitamin A/triglyceride ratio also invariably increased between 6 and 24 hr in the Sf20-30 subfraction, reflecting the formation of vitamin A-rich \"remnants\" as intermediate species in the catabolism of chylomicrons and VLDL. Among those with mild to moderate endogenous hypertriglyceridemia the Sf greater than 400 vitamin A/triglyceride ratio declined between 6 and 24 hr, reflecting the efficient passage of the vitamin A through this fraction and/or continued secretion of Sf greater than 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf greater than 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-beta disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf greater than 400 regardless of the degree of antecedent hypertriglyceridemia. Although additional experiments disclosed a similar delay in both vitamin A and triglyceride assimilation when basal triglyceride levels were high in these subjects, marked reduction of triglyceride levels did not correct the rise in the Sf greater than 400 vitamin A/triglyceride ratio between 6 and 24 hr. Experiments employing preparative electrophoresis confirmed the identity of VLDL containing a high vitamin A/triglyceride ratio with the beta-VLDL which accumulate in broad-beta disease...", "contents": "Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia). Chylomicron \"remnants\" are formed by the selective removal of triglyceride catalyzed by lipoprotein lipase. To investigate a possible defect in the clearance of these remnants in the pathophysiology of broad-beta disease (type III hyperlipoproteinemia), subjects with this disorder and comparison subjects with endogenous hypertriglyceridemia (and type IV lipoprotein patterns) ingested an oral fat load (corn oil: cocoa butter, 1:1, 50 g/sq M) containing retinyl ester, 100 mg, with or without 15 muCi 15-(14) C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf more than 400) and very low density lipoproteins (VLDS, Sf20-400) over the ensuing 24-72 hr. Vitamin A was chosen as a marker for exogenous sterol assimilation since, like cholesterol, it is absorbed in the small intestine and cosecreted in esterified form with triglyceride in the chylomicron core; however, unlike cholesterol, once having been removed by the liver, it cannot be recycled inot VLDL, but subsequently circulates only as a complex with the high density retinol binding protein. Thus measurements of the vitamin A/triglyceride ratio in Sf greater than 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins. These studies confirmed the intital concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf greater than 20 vitamin A in VLDL 24 hr after its ingestion. The vitamin A/triglyceride ratio also invariably increased between 6 and 24 hr in the Sf20-30 subfraction, reflecting the formation of vitamin A-rich \"remnants\" as intermediate species in the catabolism of chylomicrons and VLDL. Among those with mild to moderate endogenous hypertriglyceridemia the Sf greater than 400 vitamin A/triglyceride ratio declined between 6 and 24 hr, reflecting the efficient passage of the vitamin A through this fraction and/or continued secretion of Sf greater than 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf greater than 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-beta disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf greater than 400 regardless of the degree of antecedent hypertriglyceridemia. Although additional experiments disclosed a similar delay in both vitamin A and triglyceride assimilation when basal triglyceride levels were high in these subjects, marked reduction of triglyceride levels did not correct the rise in the Sf greater than 400 vitamin A/triglyceride ratio between 6 and 24 hr. Experiments employing preparative electrophoresis confirmed the identity of VLDL containing a high vitamin A/triglyceride ratio with the beta-VLDL which accumulate in broad-beta disease..."} {"id": "PMID:181658", "title": "The effect of bacterial infections on ketone concentrations in rat liver and blood and on free fatty acid concentrations in rat blood.", "content": "The concentrations of cytoplasmic lactate and pyruvate and the NAD+/NADH ratio and the concentrations of mitochondrial acetoacetate, beta-hydroxybutyrate, and the NAD+/NADH ratio were determined in normal, fed, and fasted rats, and in rats infected with Streptococcus pneumoniae, Francisella tularensis, and Salmonella typhimurium. The various infections were found to have little or no effect on the cytoplasmic parameters. In normal rats, fasting caused a marked increase in blood and hepatic ketone concentration and in serum free fatty acid content. Fasted infected rats, however, did not show the increase in ketone bodies or serum free fatty acids normally associated with fasting alone. The mitochondrial NAD+/NADH ratio increased as the infections progressed, reversing the normal trend. The introduction of an infection during the fasting state when ketone bodies and serum free fatty acids were elevated caused a marked depression in their concentration. These data have led to a postulation of decreased lipolysis in the infected host to account for the lowered hepatic and blood ketone bodies and the decreased level of serum free fatty acids.", "contents": "The effect of bacterial infections on ketone concentrations in rat liver and blood and on free fatty acid concentrations in rat blood. The concentrations of cytoplasmic lactate and pyruvate and the NAD+/NADH ratio and the concentrations of mitochondrial acetoacetate, beta-hydroxybutyrate, and the NAD+/NADH ratio were determined in normal, fed, and fasted rats, and in rats infected with Streptococcus pneumoniae, Francisella tularensis, and Salmonella typhimurium. The various infections were found to have little or no effect on the cytoplasmic parameters. In normal rats, fasting caused a marked increase in blood and hepatic ketone concentration and in serum free fatty acid content. Fasted infected rats, however, did not show the increase in ketone bodies or serum free fatty acids normally associated with fasting alone. The mitochondrial NAD+/NADH ratio increased as the infections progressed, reversing the normal trend. The introduction of an infection during the fasting state when ketone bodies and serum free fatty acids were elevated caused a marked depression in their concentration. These data have led to a postulation of decreased lipolysis in the infected host to account for the lowered hepatic and blood ketone bodies and the decreased level of serum free fatty acids."} {"id": "PMID:181659", "title": "The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases. II. PTH and bone cells: bone turnover and plasma calcium regulation.", "content": "Kinetic and morphologic studies in patients with parathyroid disease, and a wide variety of studies in experimental animals indicate that one major effect of PTH is to increase the proliferation of osteoprogenitor cells into osteoclasts and so to increase bone turnover. PTH stimulates bone cells by increasing cell membrane permeability to calcium and consequently increasing calcium influx and by activating membrane-bound adenyl-cyclase. It is likely that the former event precedes the latter and that calcium is the second messenger and cyclic AMP the third messenger. PTH increases the production by bone cells of lactate, citric and carbonic acids, lysosomal enzymes, collagenase, and hyaluronic acid, some or all of which are concerned in the mechanism of bone resorption. With the exception of lactate which probably comes mainly from osteocytes, the increase in metabolic activity is largely due to the increase in the number of osteoclasts. There is also ultrastructural, biochemical, and biophysical evidence that PTH stimulates existing osteoclasts, but this most likely represents the transformation of inactive cells into an active state, and is a transient and nonsustainable effect. As yet, there is no evidence that either increased osteoprogenitor cell proliferation or increased osteoclast activity is mediated by adenyl-cyclase activation. PTH also acts on the deep osteocyte to cause rapid mobilization of calcium from the zone of hypomineralized metabolically active perilacunar bone. This effect is mediated by adenyl-cyclase activation and is preceded by a slight fall in plasma calcium probably due to the movement of calcium into bone cells. The function of this rapid hypercalcemic response to PTH is correct errors in the prevailing steady-state level of plasma calcium...", "contents": "The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases. II. PTH and bone cells: bone turnover and plasma calcium regulation. Kinetic and morphologic studies in patients with parathyroid disease, and a wide variety of studies in experimental animals indicate that one major effect of PTH is to increase the proliferation of osteoprogenitor cells into osteoclasts and so to increase bone turnover. PTH stimulates bone cells by increasing cell membrane permeability to calcium and consequently increasing calcium influx and by activating membrane-bound adenyl-cyclase. It is likely that the former event precedes the latter and that calcium is the second messenger and cyclic AMP the third messenger. PTH increases the production by bone cells of lactate, citric and carbonic acids, lysosomal enzymes, collagenase, and hyaluronic acid, some or all of which are concerned in the mechanism of bone resorption. With the exception of lactate which probably comes mainly from osteocytes, the increase in metabolic activity is largely due to the increase in the number of osteoclasts. There is also ultrastructural, biochemical, and biophysical evidence that PTH stimulates existing osteoclasts, but this most likely represents the transformation of inactive cells into an active state, and is a transient and nonsustainable effect. As yet, there is no evidence that either increased osteoprogenitor cell proliferation or increased osteoclast activity is mediated by adenyl-cyclase activation. PTH also acts on the deep osteocyte to cause rapid mobilization of calcium from the zone of hypomineralized metabolically active perilacunar bone. This effect is mediated by adenyl-cyclase activation and is preceded by a slight fall in plasma calcium probably due to the movement of calcium into bone cells. The function of this rapid hypercalcemic response to PTH is correct errors in the prevailing steady-state level of plasma calcium..."} {"id": "PMID:181661", "title": "[Comparative effect of various chloroactive compounds on the enzyme systems of Bacillus anthracoides spores].", "content": "The effect of various chloroactive compounds containing equal amounts of chlorine on respiration enzymes was studied in the spores of Bacillus anthracoides 96. These compounds inhibited the activity of malate dehydrogenase, fumarase, and aconitase but stimulated the activity of glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and ketoglutarate dehydrogenase. Therefore, the action of these compounds is rather specific, and the inhibition of the activity of some enzymes is one of the factors causing the sporocidal effect.", "contents": "[Comparative effect of various chloroactive compounds on the enzyme systems of Bacillus anthracoides spores]. The effect of various chloroactive compounds containing equal amounts of chlorine on respiration enzymes was studied in the spores of Bacillus anthracoides 96. These compounds inhibited the activity of malate dehydrogenase, fumarase, and aconitase but stimulated the activity of glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and ketoglutarate dehydrogenase. Therefore, the action of these compounds is rather specific, and the inhibition of the activity of some enzymes is one of the factors causing the sporocidal effect."} {"id": "PMID:181663", "title": "Prostaglandins, possible mediators of the effects of oestrogens on luteinizing hormone output.", "content": "A possible mechanism for the positive and negative feed-back effects of oestrogen on luteinizing hormone (LH) output is suggested. It is proposed that oestrogens may influence prostaglandin synthesis in the hypothalamus in relation to LH releasing hormone (LH.RH) synthesis and release. Changes in oestrogen level or in the oestrogen to progesterone ratio may alter the ratios of prostaglandin concentrations in the hypothalamus, and so modulate LH.RH output through effects on sympathetic neurotransmission, protein synthesis or LH.RH release.", "contents": "Prostaglandins, possible mediators of the effects of oestrogens on luteinizing hormone output. A possible mechanism for the positive and negative feed-back effects of oestrogen on luteinizing hormone (LH) output is suggested. It is proposed that oestrogens may influence prostaglandin synthesis in the hypothalamus in relation to LH releasing hormone (LH.RH) synthesis and release. Changes in oestrogen level or in the oestrogen to progesterone ratio may alter the ratios of prostaglandin concentrations in the hypothalamus, and so modulate LH.RH output through effects on sympathetic neurotransmission, protein synthesis or LH.RH release."} {"id": "PMID:181668", "title": "Fine structure of the URA2 locus in Saccharomyces cerevisiae. II. Meiotic and mitotic mapping studies.", "content": "The URA2 locus codes for a multifunctional enzyme complex carrying aspartate transcarbamylase (ATCase) and carbamyly phosphate synthetase (CPSase) activities. Three different types of ura2 mutants were tested in meiotic and mitotic recombination experiments: ura2A mutants devoid of ATCase activity, ura2C mutants devoid of CPSase activity and ura2B mutants devoid of both activities. All the ura2A mutations were found to be clustered at one end of the URA2 locus, called zone A, while the ura2C mutations were localized in a region at the other end, called zone C. All but two ura2B mutations (most of them suppressible) were distributed throughout zone C; the two ura2B exceptions which are small deletions, mapped in zone A. On the meiotic as well as on the mitotic map an intermediary or dead-space zone is located between zones A and C. No mutation has yet been found to map in this zone. The relative lengths of the three zones A, intermediary and C are 1 :2-3 :3-4, respectively. These data are consistent with the hypothesis that the URA2 locus consisting of at least two cistrons: C (CPSase) and A (ATCase), is transcribed into a single polycistronic message in the direction C to A. However, alternative hypotheses in reference to Peterson and MacLaughlin's observations (1973) are discussed.", "contents": "Fine structure of the URA2 locus in Saccharomyces cerevisiae. II. Meiotic and mitotic mapping studies. The URA2 locus codes for a multifunctional enzyme complex carrying aspartate transcarbamylase (ATCase) and carbamyly phosphate synthetase (CPSase) activities. Three different types of ura2 mutants were tested in meiotic and mitotic recombination experiments: ura2A mutants devoid of ATCase activity, ura2C mutants devoid of CPSase activity and ura2B mutants devoid of both activities. All the ura2A mutations were found to be clustered at one end of the URA2 locus, called zone A, while the ura2C mutations were localized in a region at the other end, called zone C. All but two ura2B mutations (most of them suppressible) were distributed throughout zone C; the two ura2B exceptions which are small deletions, mapped in zone A. On the meiotic as well as on the mitotic map an intermediary or dead-space zone is located between zones A and C. No mutation has yet been found to map in this zone. The relative lengths of the three zones A, intermediary and C are 1 :2-3 :3-4, respectively. These data are consistent with the hypothesis that the URA2 locus consisting of at least two cistrons: C (CPSase) and A (ATCase), is transcribed into a single polycistronic message in the direction C to A. However, alternative hypotheses in reference to Peterson and MacLaughlin's observations (1973) are discussed."} {"id": "PMID:181669", "title": "Division delay and DNA degradation after mutagen treatment of the yeast, Saccharomyces cerevisiae.", "content": "The treatment of the yeast mutant TMP1-1, which is capable of incorporating low levels of 3H-thymidine-5' - monophosphate with UV light and ethyl methane sulphonate resulted in division delay when cultures were reinnoculated into fresh medium. The initiation of cell division was accompanied by the degradation of up to 20% of the nuclear DNA fraction. The period of DNA degradation correlates closely with the time at which yeast cultures undergo mitotic recombination and appears to represent the degradation of DNA during a post-replication repair process.", "contents": "Division delay and DNA degradation after mutagen treatment of the yeast, Saccharomyces cerevisiae. The treatment of the yeast mutant TMP1-1, which is capable of incorporating low levels of 3H-thymidine-5' - monophosphate with UV light and ethyl methane sulphonate resulted in division delay when cultures were reinnoculated into fresh medium. The initiation of cell division was accompanied by the degradation of up to 20% of the nuclear DNA fraction. The period of DNA degradation correlates closely with the time at which yeast cultures undergo mitotic recombination and appears to represent the degradation of DNA during a post-replication repair process."} {"id": "PMID:181672", "title": "[Electron microscopic study of natural SiO2 particles and SiO2 particles isolated from rat lung].", "content": "Natural SiO2 particles of 0--4, 0--5 and 5--10 micron of size were investigated by the aid of transmission and scanning electron microscope. Silicosis in rats was induced with SiO2 particles of 0--5 micron of size. After 18 month SiO2 was isolated from the silicotic lung and investigated by the aid of transmission and scanning electron microscopy and with electronmicroscopic diffraction technique. Natural and isolated from silcotic lung SiO granules were divided into different groups according to their planimetrycally measured area, and excentricity calculated from their diameter. It was established, that division of silica particles isolated from lungs became different as compared to the natural silica-dust. Among the silicadust isolated from silicotic lungs of rats proportion of finer granules is much higher than in natural silica-dust-fraction. Granules isolated from lung have rounded edges and part of them shows a decrease of electrondensity. Majority of particules of 0,01 micron of size appears to be isolated in the material got from the silicotic lung.", "contents": "[Electron microscopic study of natural SiO2 particles and SiO2 particles isolated from rat lung]. Natural SiO2 particles of 0--4, 0--5 and 5--10 micron of size were investigated by the aid of transmission and scanning electron microscope. Silicosis in rats was induced with SiO2 particles of 0--5 micron of size. After 18 month SiO2 was isolated from the silicotic lung and investigated by the aid of transmission and scanning electron microscopy and with electronmicroscopic diffraction technique. Natural and isolated from silcotic lung SiO granules were divided into different groups according to their planimetrycally measured area, and excentricity calculated from their diameter. It was established, that division of silica particles isolated from lungs became different as compared to the natural silica-dust. Among the silicadust isolated from silicotic lungs of rats proportion of finer granules is much higher than in natural silica-dust-fraction. Granules isolated from lung have rounded edges and part of them shows a decrease of electrondensity. Majority of particules of 0,01 micron of size appears to be isolated in the material got from the silicotic lung."} {"id": "PMID:181673", "title": "[Biochemical form of a paraneoplastic Cushing's syndrome (author's transl)].", "content": "Paraneoplastic hypercorticism appears either as a fullfledged Cushing's syndrome with adiposity of the trunk, moon face and striae or as a biochemical form with hypokalemic alkalosis, adynamia and muscular atrophy. A form of the disease with the biochemical type in bronichial carcinoma is reported, which emphasizes also the significance of paraneoplastic syndromes for the early diagnosis of neoplasia.", "contents": "[Biochemical form of a paraneoplastic Cushing's syndrome (author's transl)]. Paraneoplastic hypercorticism appears either as a fullfledged Cushing's syndrome with adiposity of the trunk, moon face and striae or as a biochemical form with hypokalemic alkalosis, adynamia and muscular atrophy. A form of the disease with the biochemical type in bronichial carcinoma is reported, which emphasizes also the significance of paraneoplastic syndromes for the early diagnosis of neoplasia."} {"id": "PMID:181670", "title": "[The character of the distribution of chloroplast DNA from higher plants in a cesium chloride density gradient].", "content": "The nature of distribution of the chloroplast DNA from three species of higher plants (Sp. oleracea, N. tabacum, P. sativum) in the CsCl density gradient has been investigated DNA preparations isolated from the fractions of chloroplasts completely deprived of the admixtures of nuclei and mitochondria are characterized by symmetric distribution in the density gradient. Fragmentation of chloroplast DNA of higher plants is not accompanied by the appearance of the discrete satellite components. It has been shown that the satellite DNA component found in the fraction of the unpurified chloroplasts are entirely mitochondrial DNA.", "contents": "[The character of the distribution of chloroplast DNA from higher plants in a cesium chloride density gradient]. The nature of distribution of the chloroplast DNA from three species of higher plants (Sp. oleracea, N. tabacum, P. sativum) in the CsCl density gradient has been investigated DNA preparations isolated from the fractions of chloroplasts completely deprived of the admixtures of nuclei and mitochondria are characterized by symmetric distribution in the density gradient. Fragmentation of chloroplast DNA of higher plants is not accompanied by the appearance of the discrete satellite components. It has been shown that the satellite DNA component found in the fraction of the unpurified chloroplasts are entirely mitochondrial DNA."} {"id": "PMID:181674", "title": "Studies on DNA repair in early spermatid stages of male mice after in vivo treatment with methyl-, ethyl-, propyl-, and isopropyl methanesulfonate.", "content": "In vivo DNA repair occurring in early spermatid stages of the mouse has been studied with four mutagens that are chemical homologs: MMS, EMS, PMS and IMS. Using the well-studied sequence of events that occurs during spermatogenesis and spermiogenesis in the mouse, aatids was measured by the unscheduled incorporation of [3H]dT into these germ cells which were recovered from the caudal epididymides 16 days after chemical treatment. Purification of the caudal sperm DNA at this time verified that the [3H]dT was incorporated into the DNA. For each chemical mutagen a study was made on the level of DNA repair occurring in early spermatids as a function of the administered, in vivo dose. Within experimental errors, all four chemicals produced a linear increase in DNA repair in early spermatids with increasing dose. Only the highest dose of MMS (100 mg/kg) produced a greater repair response than expected for a linear curve. At equimolar doses the most effective chemical in inducing DNA repair was MMS, followed by EMS, IMS and PMS. When testicular injections of [3H]dT were given at the same time as the intraperitoneal injections of the mutagens, the amount of unscheduled incorporation of [3H]dT into the DNA of early spermatids was maximized. Since [3H]dT has been shown to be available for incorporation into germ-cell DNA for only approximately 1 h after injection, all four mutagens must reach the DNA of early spermatids and begin producing \"repairable\" lesions within 1 h after treatment. The amount of DNA repair occurring at later times after chemical treatment of early spermatids was studied by testicular injections of [3H]dT 1/2, 1, 2 and 3 days after chemical treatment. Repair was still occurring in the early spermatids at 3 days post-treatment; this repair is most likely a manifestation of the finite rate of the repair process rather than resulting from newly alkylated DNA. For MMS and EMS there was a rapid decrease in the level of DNA repair in the first 1/2 day following treatment. This was followed by a much slower, exponential decrease in the level of repair out to 3 days post-treatment. The curves suggest that the amount of repair is proportional to the number of repairable lesions still present in the DNA. For PMS and IMS the level of repair decreases rapidly in the first 1/2 day after treatment and thereafter remains relatively constant through 3 days post-treatment. With all four mutagens, DNA repair in early spermatids was detectable at doses 5 to 10 times lower than those required to observe other genetic end points such as dominant lethals, translocations and specific-locus mutations in any germ-cell stage. The sensitivity of detection of in vivo DNA repair in the germ cells of male mice makes such a system a useful adjunct to other genetic tests for studying chemical mutagenesis in mammals.", "contents": "Studies on DNA repair in early spermatid stages of male mice after in vivo treatment with methyl-, ethyl-, propyl-, and isopropyl methanesulfonate. In vivo DNA repair occurring in early spermatid stages of the mouse has been studied with four mutagens that are chemical homologs: MMS, EMS, PMS and IMS. Using the well-studied sequence of events that occurs during spermatogenesis and spermiogenesis in the mouse, aatids was measured by the unscheduled incorporation of [3H]dT into these germ cells which were recovered from the caudal epididymides 16 days after chemical treatment. Purification of the caudal sperm DNA at this time verified that the [3H]dT was incorporated into the DNA. For each chemical mutagen a study was made on the level of DNA repair occurring in early spermatids as a function of the administered, in vivo dose. Within experimental errors, all four chemicals produced a linear increase in DNA repair in early spermatids with increasing dose. Only the highest dose of MMS (100 mg/kg) produced a greater repair response than expected for a linear curve. At equimolar doses the most effective chemical in inducing DNA repair was MMS, followed by EMS, IMS and PMS. When testicular injections of [3H]dT were given at the same time as the intraperitoneal injections of the mutagens, the amount of unscheduled incorporation of [3H]dT into the DNA of early spermatids was maximized. Since [3H]dT has been shown to be available for incorporation into germ-cell DNA for only approximately 1 h after injection, all four mutagens must reach the DNA of early spermatids and begin producing \"repairable\" lesions within 1 h after treatment. The amount of DNA repair occurring at later times after chemical treatment of early spermatids was studied by testicular injections of [3H]dT 1/2, 1, 2 and 3 days after chemical treatment. Repair was still occurring in the early spermatids at 3 days post-treatment; this repair is most likely a manifestation of the finite rate of the repair process rather than resulting from newly alkylated DNA. For MMS and EMS there was a rapid decrease in the level of DNA repair in the first 1/2 day following treatment. This was followed by a much slower, exponential decrease in the level of repair out to 3 days post-treatment. The curves suggest that the amount of repair is proportional to the number of repairable lesions still present in the DNA. For PMS and IMS the level of repair decreases rapidly in the first 1/2 day after treatment and thereafter remains relatively constant through 3 days post-treatment. With all four mutagens, DNA repair in early spermatids was detectable at doses 5 to 10 times lower than those required to observe other genetic end points such as dominant lethals, translocations and specific-locus mutations in any germ-cell stage. The sensitivity of detection of in vivo DNA repair in the germ cells of male mice makes such a system a useful adjunct to other genetic tests for studying chemical mutagenesis in mammals."} {"id": "PMID:181671", "title": "[Phosphorylation of lysine-rich histones by swine brain histokinase].", "content": "The phosphorylation of lysine-rich histones F1, F2a2 and F2b of calf thymus has been investigated using homogeneous histone kinase from pig brain. 32P-labelled phosphopeptides from tryptic digests of corresponding histones were obtained. According to N-terminal analysis and the quantitative determination of amino acid composition of the obtained radioactive peptides the sites of phosphorylation were identified in the primary structure of lysine-rich histones, namely, Ser-38 for the polypeptide chain of histone F1, Ser-19 or 18 for histone F2a2 and Ser-14 and 36 for histone F2b. Thus, the high specificity of brain histone kinase in vitro was demonstrated.", "contents": "[Phosphorylation of lysine-rich histones by swine brain histokinase]. The phosphorylation of lysine-rich histones F1, F2a2 and F2b of calf thymus has been investigated using homogeneous histone kinase from pig brain. 32P-labelled phosphopeptides from tryptic digests of corresponding histones were obtained. According to N-terminal analysis and the quantitative determination of amino acid composition of the obtained radioactive peptides the sites of phosphorylation were identified in the primary structure of lysine-rich histones, namely, Ser-38 for the polypeptide chain of histone F1, Ser-19 or 18 for histone F2a2 and Ser-14 and 36 for histone F2b. Thus, the high specificity of brain histone kinase in vitro was demonstrated."} {"id": "PMID:181675", "title": "School failure and deafness after \"silent\" congenital cytomegalovirus infection.", "content": "We found IgM antibody directed against cytomegalovirus in the umbilical-cord blood of 53 of 8644 newborns. Forty-four of the 53 had psychometric and pediatric evaluations at 3.5 to 7.0 years of age. The group's mean IQ was 102.5+/-22.4 (+/-S.D.), whereas in matched controls it was 111.7 (PC 0.025). Bilateral hearing loss was present in five of 40 children with antibody against cytomegalovirus and in one of 44 matched controls without antibody (P less than 0.1). Three of the antibody-positive children, however, had profound deafness, an abnormality that occurs once in approximately 1000 children. The predicted school failure rate, based on IQ, behavioral, neurologic and auditory test data, was 2.7 times that of matched socioeconomic controls and eight times that of randomly selected controls. We conclude that clinically inapparent congenital cytomegalovirus infection can adversely affect central-nervous-system development.", "contents": "School failure and deafness after \"silent\" congenital cytomegalovirus infection. We found IgM antibody directed against cytomegalovirus in the umbilical-cord blood of 53 of 8644 newborns. Forty-four of the 53 had psychometric and pediatric evaluations at 3.5 to 7.0 years of age. The group's mean IQ was 102.5+/-22.4 (+/-S.D.), whereas in matched controls it was 111.7 (PC 0.025). Bilateral hearing loss was present in five of 40 children with antibody against cytomegalovirus and in one of 44 matched controls without antibody (P less than 0.1). Three of the antibody-positive children, however, had profound deafness, an abnormality that occurs once in approximately 1000 children. The predicted school failure rate, based on IQ, behavioral, neurologic and auditory test data, was 2.7 times that of matched socioeconomic controls and eight times that of randomly selected controls. We conclude that clinically inapparent congenital cytomegalovirus infection can adversely affect central-nervous-system development."} {"id": "PMID:181676", "title": "C-type virus expression in systemic lupus erythematosus.", "content": "Kidneys from patients with lupus nephropathy, non-lupus immune-complex glomerulonephritis and other renal diseases were examined by indirect immunofluorescence for antigens related to a C-type virus from human cells (HEL-12 virus). All 11 specimens of lupus nephropathy contained HEL-12 virus antigens deposited in the same pattern as the immune complexes. The intensity of immunofluorescence with anti-HEL-12 virus serum correlated with the extent of immune-complex deposition. In contrast, nine renal lesions other than lupus nephropathy and seven normal tissues did not react with anti-HEL-12 virus serum. Antibody eluted from one kidney with lupus nephropathy reacted by indirect immunofluorescence with human and dog cells infected with HEL-12 virus but not with uninfected control cells. These findings demonstrate a specific association of lupus nephropathy with a C-type viral antigen that is deposited as antigen-antiviral antibody complex.", "contents": "C-type virus expression in systemic lupus erythematosus. Kidneys from patients with lupus nephropathy, non-lupus immune-complex glomerulonephritis and other renal diseases were examined by indirect immunofluorescence for antigens related to a C-type virus from human cells (HEL-12 virus). All 11 specimens of lupus nephropathy contained HEL-12 virus antigens deposited in the same pattern as the immune complexes. The intensity of immunofluorescence with anti-HEL-12 virus serum correlated with the extent of immune-complex deposition. In contrast, nine renal lesions other than lupus nephropathy and seven normal tissues did not react with anti-HEL-12 virus serum. Antibody eluted from one kidney with lupus nephropathy reacted by indirect immunofluorescence with human and dog cells infected with HEL-12 virus but not with uninfected control cells. These findings demonstrate a specific association of lupus nephropathy with a C-type viral antigen that is deposited as antigen-antiviral antibody complex."} {"id": "PMID:181677", "title": "Susceptibility of chickens to avian encephalomyelitis virus. III. Behavior of the virus in growing chicks.", "content": "A chick embryo-adapted strain of avian encephalomyelitis virus was inoculated subcutaneously and orally into 40-day-old (middle-aged) and 110-day-old (advanced-aged) chicks to examine the behavior of the virus in the chick body. In the middle-aged chicks, the virus appeared in the muscle at the site of inoculation, liver, spleen, pancreas, lumbar and cervical portions of the spinal cord, and brain 1 approximately 9 days after subcutaneous inoculation, and remained mostly in the central nervous system up to 17 days after the inoculation. The virus was found in large amounts in the muscle at the site of inoculation (10(3.1)), lumbar portion (10(2.5)) and cervical portion (10(2.1)) of the spinal cord, brain (10(1.9)), and in minute amounts in the other organs examined. It appeared in 11 of 21 organs examined. In the middle-aged chicks inoculated by the oral route, the virus was detected transiently in small amounts from esophagus, pancreas, and rectum 4 approximately 14 days after inoculation. In the advanced-aged chicks inoculated by the subcutaneous route, the virus was detected in titer of 10(2.1) approximately 10(3.0) from the muscle at the site of inoculation 2 approximately 7 days after inoculation. The virus was also found sporadically in several organs up to 17 days after inoculation. In the advanced-aged chicks inoculated by the oral route, no virus appeared in any organ, but these chicks turned to be weakly positive for neutralizing antibody in the 4th or later week after inoculation.", "contents": "Susceptibility of chickens to avian encephalomyelitis virus. III. Behavior of the virus in growing chicks. A chick embryo-adapted strain of avian encephalomyelitis virus was inoculated subcutaneously and orally into 40-day-old (middle-aged) and 110-day-old (advanced-aged) chicks to examine the behavior of the virus in the chick body. In the middle-aged chicks, the virus appeared in the muscle at the site of inoculation, liver, spleen, pancreas, lumbar and cervical portions of the spinal cord, and brain 1 approximately 9 days after subcutaneous inoculation, and remained mostly in the central nervous system up to 17 days after the inoculation. The virus was found in large amounts in the muscle at the site of inoculation (10(3.1)), lumbar portion (10(2.5)) and cervical portion (10(2.1)) of the spinal cord, brain (10(1.9)), and in minute amounts in the other organs examined. It appeared in 11 of 21 organs examined. In the middle-aged chicks inoculated by the oral route, the virus was detected transiently in small amounts from esophagus, pancreas, and rectum 4 approximately 14 days after inoculation. In the advanced-aged chicks inoculated by the subcutaneous route, the virus was detected in titer of 10(2.1) approximately 10(3.0) from the muscle at the site of inoculation 2 approximately 7 days after inoculation. The virus was also found sporadically in several organs up to 17 days after inoculation. In the advanced-aged chicks inoculated by the oral route, no virus appeared in any organ, but these chicks turned to be weakly positive for neutralizing antibody in the 4th or later week after inoculation."} {"id": "PMID:181678", "title": "Isolation and properties of reovirus from cattle in an outbreak of acute respiratory disease.", "content": "A cytopathogenic virus was isolated in the primary culture of bovine kidney cells from a nasal swab of affected calves in an outbreak of acute respiratory disease in Japan in 1971. It agglutinated human type O erythrocytes and produced cytoplasmic inclusion bodies. Viral replication was inhibited by 5-iodo-2'-deoxyuridine, indicating that the viral nucleic acid was RNA. The virus was resistant to ether, chloroform, sodium deoxycholate, and acid, and passed readily through Sartorius' membrane filter 100 nm in pore size, but not through the filter 50 nm in pore size. Electron microscopy showed many spherical particles 60 approximately 75 nm in diameter with a double-layered capsid in a sample taken at a buoyant density of 1.34 produced by CaCl equilibrium centrifugation. The virus suspended in 1M MgCl2 solution was stable against heating at 50 degrees C for 30 minutes, but not against freezing at -20 degrees C for 60 minutes. The virus was resistant to, and increased in infectivity after, treatment with 0.063 approximately 1.0% trypsin. These properties were consistent with those established for the reoviruses. Most affected cattle showed a significant rise of antibody titer against reovirus and bovine respiratory syncytial virus, whereas only a few of them presented a serological evidence for recent infection with parainfluenza virus type 3, bovine adenovirus type 7, and bovine parovirus.", "contents": "Isolation and properties of reovirus from cattle in an outbreak of acute respiratory disease. A cytopathogenic virus was isolated in the primary culture of bovine kidney cells from a nasal swab of affected calves in an outbreak of acute respiratory disease in Japan in 1971. It agglutinated human type O erythrocytes and produced cytoplasmic inclusion bodies. Viral replication was inhibited by 5-iodo-2'-deoxyuridine, indicating that the viral nucleic acid was RNA. The virus was resistant to ether, chloroform, sodium deoxycholate, and acid, and passed readily through Sartorius' membrane filter 100 nm in pore size, but not through the filter 50 nm in pore size. Electron microscopy showed many spherical particles 60 approximately 75 nm in diameter with a double-layered capsid in a sample taken at a buoyant density of 1.34 produced by CaCl equilibrium centrifugation. The virus suspended in 1M MgCl2 solution was stable against heating at 50 degrees C for 30 minutes, but not against freezing at -20 degrees C for 60 minutes. The virus was resistant to, and increased in infectivity after, treatment with 0.063 approximately 1.0% trypsin. These properties were consistent with those established for the reoviruses. Most affected cattle showed a significant rise of antibody titer against reovirus and bovine respiratory syncytial virus, whereas only a few of them presented a serological evidence for recent infection with parainfluenza virus type 3, bovine adenovirus type 7, and bovine parovirus."} {"id": "PMID:181679", "title": "Separation and properties of enterovirus and reovirus recovered from a fecal sample of calf with diarrhea.", "content": "In April, 1971, a disease with pyrexia and diarrhea as main symptoms broke out collectively among calves. Fecal samples were collected from calves involved and inoculated into bovine kidney (BK) cell cultures. As a result, the diarrheal feces of one calf were suspected to contain two agents simultaneously. One agent (C-121 E strain) was isolated from the primary infected BK cell culture fluid by terminal dilution passages. It had been predominant in replication and shown a cytopathic effect which gave rise to a granular appearance in the early stage of culture. The other agent (C-121 R strain) was isolated from the primary infected BK cell culture fluid by neutralizing the C-121 E strain contained in this fluid with antiserum against this strain. It caused cytoplasmic inclusion bodies to form. On the basis of their physico-chemical properties, the C-121 E strain was identified as bovine enterovirus and the C-121 R strain as reovirus. Serological tests indicated that some of the affected calves had been infected not only with the two strains isolated, but also with bovine viral diarrhea virus, bovine adenovirus type 7, and bovine parvovirus.", "contents": "Separation and properties of enterovirus and reovirus recovered from a fecal sample of calf with diarrhea. In April, 1971, a disease with pyrexia and diarrhea as main symptoms broke out collectively among calves. Fecal samples were collected from calves involved and inoculated into bovine kidney (BK) cell cultures. As a result, the diarrheal feces of one calf were suspected to contain two agents simultaneously. One agent (C-121 E strain) was isolated from the primary infected BK cell culture fluid by terminal dilution passages. It had been predominant in replication and shown a cytopathic effect which gave rise to a granular appearance in the early stage of culture. The other agent (C-121 R strain) was isolated from the primary infected BK cell culture fluid by neutralizing the C-121 E strain contained in this fluid with antiserum against this strain. It caused cytoplasmic inclusion bodies to form. On the basis of their physico-chemical properties, the C-121 E strain was identified as bovine enterovirus and the C-121 R strain as reovirus. Serological tests indicated that some of the affected calves had been infected not only with the two strains isolated, but also with bovine viral diarrhea virus, bovine adenovirus type 7, and bovine parvovirus."} {"id": "PMID:181680", "title": "Increased intestinal absorption in the rat caused by sodium lauryl sulphate, and its possible relation to the cAMP system.", "content": "The increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime caused by 17 mM sodium lauryl sulphate (SLS) from jejunal loops of anaesthetized rats were significantly reduced if sodium and chloride (Briseid et al., 1974) or chloride and bicarbonate were replaced by other ions in the loop fluid. Separate substitutions of sodium, chloride of bicarbonate did not significantly alter the SLS-caused absorption, except that the substitution of choline for sodium reduced the absorption of pralidoxime, both in the presence and in the absence of SLS. The increases in the absorption of phenolsulphonphthalein and pralidoxime caused by SLS were potentiated by theophylline (25 mM) and reduced by imidazole (25 mM). The addition of dibutyryl cyclic AMP (2.5 mM) to the loop fluid increased this absorption of the test substances. This effect was reduced by imidazole, but under the experimental conditions it was not potentiated by theophylline. Determinations of cyclic AMP in the rat intestinal mucosa showed that the level of this substance was significantly higher in the presence than in the absence of SLS. The experimental conditions were as described for the absorption experiments. It is concluded that the data obtained support the idea of an increased level of cyclic AMP as the main basis for the effect of SLS on the absorption.", "contents": "Increased intestinal absorption in the rat caused by sodium lauryl sulphate, and its possible relation to the cAMP system. The increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime caused by 17 mM sodium lauryl sulphate (SLS) from jejunal loops of anaesthetized rats were significantly reduced if sodium and chloride (Briseid et al., 1974) or chloride and bicarbonate were replaced by other ions in the loop fluid. Separate substitutions of sodium, chloride of bicarbonate did not significantly alter the SLS-caused absorption, except that the substitution of choline for sodium reduced the absorption of pralidoxime, both in the presence and in the absence of SLS. The increases in the absorption of phenolsulphonphthalein and pralidoxime caused by SLS were potentiated by theophylline (25 mM) and reduced by imidazole (25 mM). The addition of dibutyryl cyclic AMP (2.5 mM) to the loop fluid increased this absorption of the test substances. This effect was reduced by imidazole, but under the experimental conditions it was not potentiated by theophylline. Determinations of cyclic AMP in the rat intestinal mucosa showed that the level of this substance was significantly higher in the presence than in the absence of SLS. The experimental conditions were as described for the absorption experiments. It is concluded that the data obtained support the idea of an increased level of cyclic AMP as the main basis for the effect of SLS on the absorption."} {"id": "PMID:181681", "title": "Catecholamine receptor agonists: effects on motor activity and rate of tyrosine hydroxylation in mouse brain.", "content": "Motor activity during the first 5 min in a motility meter was measured in mice given 0.025-3.2 mg/kg of the dopamine and noradrenaline receptor agonists apomorphine and clonidine, respectively. The accumulation of Dopa, as induced by the inhibitor of aromatic amino acid decarboxylase, NSD 1015, was measured in parallel in two dopamine-rich regions, i.e. the limbic system and the corpus striatum, and in two noradrenaline-rich regions, i.e. the neocortex and the lower brain stem. Low doses (0.025-0.2 mg/kg) of apomorphine reduced locomotion in a dose-dependent manner, while the reduction after higher doses was less pronounced, indicating a biphasic dose-response relationship. Clonidine caused a dose-dependent locomotor depression. When low doses of the two drugs were combined, the inhibitory effect observed was at least additive. When clonidine was combined with a high dose of apomorphine (0.8 mg/kg), it caused a significant inhibition of locomotion in a dose of 0.1-0.2 mg/kg, but not after 0.8 mg/kg, indicating a biphasic dose-response relationship. Either drug given alone reduced Dopa accumulation after inhibition of its decarboxylation, in all regions, but smaller doses of apomorphine had a clearcut effect only in the dopamine-rich regions, whereas the lowest dose of clonidine investigated (0.05 mg/kg) had an inhibitory effect on Dopa formation only in the neocortex. The relationship between the dose of apomorphine and Dopa formation in the neocortex appeared biphasic, the highest dose (3.2 mg/kg) having no significant effect. Further, apomorphine in this dose accelerated the disappearance of noradrenaline after inhibition of synthesis by alpha-methyltyrosine. Reversal of reserpine-induced suppression of motor activity was taken to indicate postsynaptic receptor activation. The threshold dose of apomorphine causing reversal was 0.2 mg/kg. The inhibitory effect of e.g. 0.05 mg/kg on locomotion and on Dopa formation suggests a preferential activation of inhibitory autoregulatory dopamine receptors by low doses of this drug. A similar trend was observed for clonidine. The basal importance of dopamine neurones for the locomotor function studied in the present paper is illustrated by the marked inhibition by low doses of apomorphine. On the other hand, the observations with clonidine suggest a somewhat less striking and perhaps less direct influence of noradrenaline neurones on motor activity. Mice with a low motor activity, as induced e.g. by reserpine or, in another experiment, mice adapted to the motility meter, displayed an increased motor activity after higher doses of apomorphine (from 0.2 and 2 mg/kg, respectively), whereas all doses depressed the initial high motor activity. Probably, high motor activity requires active dopamine neurones, making this behaviour more susceptible to interference with autoregulatory mechanisms, whereas a low basal activity may be more affected by activation of postsynaptic dopamine receptors.", "contents": "Catecholamine receptor agonists: effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Motor activity during the first 5 min in a motility meter was measured in mice given 0.025-3.2 mg/kg of the dopamine and noradrenaline receptor agonists apomorphine and clonidine, respectively. The accumulation of Dopa, as induced by the inhibitor of aromatic amino acid decarboxylase, NSD 1015, was measured in parallel in two dopamine-rich regions, i.e. the limbic system and the corpus striatum, and in two noradrenaline-rich regions, i.e. the neocortex and the lower brain stem. Low doses (0.025-0.2 mg/kg) of apomorphine reduced locomotion in a dose-dependent manner, while the reduction after higher doses was less pronounced, indicating a biphasic dose-response relationship. Clonidine caused a dose-dependent locomotor depression. When low doses of the two drugs were combined, the inhibitory effect observed was at least additive. When clonidine was combined with a high dose of apomorphine (0.8 mg/kg), it caused a significant inhibition of locomotion in a dose of 0.1-0.2 mg/kg, but not after 0.8 mg/kg, indicating a biphasic dose-response relationship. Either drug given alone reduced Dopa accumulation after inhibition of its decarboxylation, in all regions, but smaller doses of apomorphine had a clearcut effect only in the dopamine-rich regions, whereas the lowest dose of clonidine investigated (0.05 mg/kg) had an inhibitory effect on Dopa formation only in the neocortex. The relationship between the dose of apomorphine and Dopa formation in the neocortex appeared biphasic, the highest dose (3.2 mg/kg) having no significant effect. Further, apomorphine in this dose accelerated the disappearance of noradrenaline after inhibition of synthesis by alpha-methyltyrosine. Reversal of reserpine-induced suppression of motor activity was taken to indicate postsynaptic receptor activation. The threshold dose of apomorphine causing reversal was 0.2 mg/kg. The inhibitory effect of e.g. 0.05 mg/kg on locomotion and on Dopa formation suggests a preferential activation of inhibitory autoregulatory dopamine receptors by low doses of this drug. A similar trend was observed for clonidine. The basal importance of dopamine neurones for the locomotor function studied in the present paper is illustrated by the marked inhibition by low doses of apomorphine. On the other hand, the observations with clonidine suggest a somewhat less striking and perhaps less direct influence of noradrenaline neurones on motor activity. Mice with a low motor activity, as induced e.g. by reserpine or, in another experiment, mice adapted to the motility meter, displayed an increased motor activity after higher doses of apomorphine (from 0.2 and 2 mg/kg, respectively), whereas all doses depressed the initial high motor activity. Probably, high motor activity requires active dopamine neurones, making this behaviour more susceptible to interference with autoregulatory mechanisms, whereas a low basal activity may be more affected by activation of postsynaptic dopamine receptors."} {"id": "PMID:181682", "title": "Conversion of angiotensin I in isolated perfused guinea-pig and rat lung.", "content": "Increasing concentrations of angiotensin I and different perfusion rates were used to study the conversion of angiotensin I in guinea-pig and rat lungs. Even the highest concentration used (32.0 muM), which is a thousand times higher than that which occurs in vivo, was unable to saturate the converting system indicating the enormous capacity of this system. SQ 20881 proved to be a reversible inhibitor of the converting system. Its effect on the angiotensin I conversion was greater in guinea-pig lungs than in rat lungs (ID50 was 40.0 nM in guinea-pig lung and above 360.0 nM in rat lungs at a substrate concentration of 38.6 nM).", "contents": "Conversion of angiotensin I in isolated perfused guinea-pig and rat lung. Increasing concentrations of angiotensin I and different perfusion rates were used to study the conversion of angiotensin I in guinea-pig and rat lungs. Even the highest concentration used (32.0 muM), which is a thousand times higher than that which occurs in vivo, was unable to saturate the converting system indicating the enormous capacity of this system. SQ 20881 proved to be a reversible inhibitor of the converting system. Its effect on the angiotensin I conversion was greater in guinea-pig lungs than in rat lungs (ID50 was 40.0 nM in guinea-pig lung and above 360.0 nM in rat lungs at a substrate concentration of 38.6 nM)."} {"id": "PMID:181683", "title": "Non-specific inhibition of membrane-ATPase by amiloride: a comparative in vivo and in vitro study with ouabain.", "content": "The submaxillary duct epithelium, which actively transports Na+ (rabbit) and, in addition, K+ and H+/HCO-/3 (rat), was used as a model epithelium to compare the effects of ouabain and amiloride on transport parameters. 1. Ouabain was only effective from the interstitial side, amiloride, however, only from the luminal side. Amiloride induced effects on transport of the ions were seen within less than 1 s, ouabain effects, however, only after minutes. 2. Ouabain inhibited in a parallel fashion the Na+ transport potential and the Na+-K+-ATPase activity. It had no effect on the Mg2+-ATPase and the HCO-/3-ATPase. 3. Amiloride also inhibited the Na+ transport potential and the Na+-K+-ATPase; however, the Na+ transport potential was significantly more sensitive to amiloride than the Na+-K+-ATPase. 4. Amiloride inhibited in a similar fashion the Na+-K+-ATPase, the Mg2+-ATPase and the HCO-/3-ATPase, but did not influence active HCO-/3 secretion. 5. It is concluded that the amiloride induced effects on the membrane ATPases are non-specific.", "contents": "Non-specific inhibition of membrane-ATPase by amiloride: a comparative in vivo and in vitro study with ouabain. The submaxillary duct epithelium, which actively transports Na+ (rabbit) and, in addition, K+ and H+/HCO-/3 (rat), was used as a model epithelium to compare the effects of ouabain and amiloride on transport parameters. 1. Ouabain was only effective from the interstitial side, amiloride, however, only from the luminal side. Amiloride induced effects on transport of the ions were seen within less than 1 s, ouabain effects, however, only after minutes. 2. Ouabain inhibited in a parallel fashion the Na+ transport potential and the Na+-K+-ATPase activity. It had no effect on the Mg2+-ATPase and the HCO-/3-ATPase. 3. Amiloride also inhibited the Na+ transport potential and the Na+-K+-ATPase; however, the Na+ transport potential was significantly more sensitive to amiloride than the Na+-K+-ATPase. 4. Amiloride inhibited in a similar fashion the Na+-K+-ATPase, the Mg2+-ATPase and the HCO-/3-ATPase, but did not influence active HCO-/3 secretion. 5. It is concluded that the amiloride induced effects on the membrane ATPases are non-specific."} {"id": "PMID:181684", "title": "Adrenal cortex adenylate cyclase. Is Ca2+ involved in ACTH stimulation?", "content": "The chelator EGTA inhibits the activation of bovine adrenal cortex adenylate cyclase by ACTH. Hormonal response is restored by addition of Ca2+, Mn2+ and other cations which are able to significantly reduce the concentration of uncomplexed EGTA in the adenylate cyclase assy medium. Time course studies reveal that the enzyme in the activated state (induced by adenylate cyclase reagents and hormone or by pretreatment with hormone) is resistant to EGTA inhibition.", "contents": "Adrenal cortex adenylate cyclase. Is Ca2+ involved in ACTH stimulation? The chelator EGTA inhibits the activation of bovine adrenal cortex adenylate cyclase by ACTH. Hormonal response is restored by addition of Ca2+, Mn2+ and other cations which are able to significantly reduce the concentration of uncomplexed EGTA in the adenylate cyclase assy medium. Time course studies reveal that the enzyme in the activated state (induced by adenylate cyclase reagents and hormone or by pretreatment with hormone) is resistant to EGTA inhibition."} {"id": "PMID:181685", "title": "Effects of stimulatory and depressant drugs on cyclic guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate levels in mouse brain.", "content": "Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.", "contents": "Effects of stimulatory and depressant drugs on cyclic guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate levels in mouse brain. Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system."} {"id": "PMID:181686", "title": "The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum.", "content": "Striatal slices were continuously superfused with L-3,5-(3)H-tyrosine (50 muCi/ml) and 4H-H2O [index of 3H-dopamine (3H-DA) synthesis] and 3H-DA estimated in 0.5 ml (2.5 min) superfusate fractions. Depolarization with 50 mM K+ for 7.5 min induced a marked increase in 3H-DA release and a biphasic effect on synthesis (slight increase in the first fraction followed by a significant decrease in the third and fourth fractions). The decrease in the rate of 4H-H2O formation induced by K+ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. Benztropine in a concentration which produced inhibition of DA uptake (10(-6) M) increased the K+ induced overflow of 3H-DA but failed to alter the inhibition of synthesis. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3H-DA uptake (10(-6) M) it potentiated 3H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. A similar effect was seen following the in vivo treatment of rats with fluphenazine (2 mg/kg; 1 1/2 h before sacrifice). The addition of exogenous DA (0.6 X 10(-6) M) or NA (10(-6) M) to the superfusion medium increased 3H-DA outflow and reduced DA synthesis while isoproterenol (10(-6) M) was without effect. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10(-6) M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10(-6) M) significantly prevented the decrease in 3H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. In addition, the effect of exogenous DA on the inhibition of synthesis was still seen in the presence of 2-amino-4-hydroxy-6,7-dimethyl-5,6,-7,8-tetrahydropteridine hydrochloride (DMPH4) (to protect against end-product inhibition). The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.", "contents": "The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Striatal slices were continuously superfused with L-3,5-(3)H-tyrosine (50 muCi/ml) and 4H-H2O [index of 3H-dopamine (3H-DA) synthesis] and 3H-DA estimated in 0.5 ml (2.5 min) superfusate fractions. Depolarization with 50 mM K+ for 7.5 min induced a marked increase in 3H-DA release and a biphasic effect on synthesis (slight increase in the first fraction followed by a significant decrease in the third and fourth fractions). The decrease in the rate of 4H-H2O formation induced by K+ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. Benztropine in a concentration which produced inhibition of DA uptake (10(-6) M) increased the K+ induced overflow of 3H-DA but failed to alter the inhibition of synthesis. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3H-DA uptake (10(-6) M) it potentiated 3H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. A similar effect was seen following the in vivo treatment of rats with fluphenazine (2 mg/kg; 1 1/2 h before sacrifice). The addition of exogenous DA (0.6 X 10(-6) M) or NA (10(-6) M) to the superfusion medium increased 3H-DA outflow and reduced DA synthesis while isoproterenol (10(-6) M) was without effect. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10(-6) M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10(-6) M) significantly prevented the decrease in 3H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. In addition, the effect of exogenous DA on the inhibition of synthesis was still seen in the presence of 2-amino-4-hydroxy-6,7-dimethyl-5,6,-7,8-tetrahydropteridine hydrochloride (DMPH4) (to protect against end-product inhibition). The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter."} {"id": "PMID:181687", "title": "Effects of diethyldithiocarbamate on the catabolism of tyrosine in the rat brain.", "content": "500 mg/kg sodium diethyldithiocarbamate (DDC) and trace quantities of uniformly labelled 14C-tyrosine were administered simultaneously to male albino rats of Porton-Wistar strain of approximately 210 g body weight. Thirty minutes later total radioactivity, the concentration and the specific activity of free tyrosine were increased both in plasma and in the brain by 40% compared with rats untreated with DDC. The incorporation of 14C from 14C-tyrosine into the fraction corresponding to the elution of glutamine-glutamate from the amberlite resin column was 80% less in the brain 30 min after DDC. The exhalation of 14CO2 was depressed by 80% in the first hour after DDC. When 14C-tyrosine was given 3.5 h after DDC the only differences between experimental and control rats were the increased incorporation of 14C into the glutamine-glutamate and aspartate fractions and the increased exhalation of 14CO2 which became significiant in the third and fourth half hour periods after the injection of 14C-tyrosine. From the experiments it is concluded that DDC, an inhibitor of dopamine-beta-hydroxylase, also interferes with the major catabolic pathway of tyrosine.", "contents": "Effects of diethyldithiocarbamate on the catabolism of tyrosine in the rat brain. 500 mg/kg sodium diethyldithiocarbamate (DDC) and trace quantities of uniformly labelled 14C-tyrosine were administered simultaneously to male albino rats of Porton-Wistar strain of approximately 210 g body weight. Thirty minutes later total radioactivity, the concentration and the specific activity of free tyrosine were increased both in plasma and in the brain by 40% compared with rats untreated with DDC. The incorporation of 14C from 14C-tyrosine into the fraction corresponding to the elution of glutamine-glutamate from the amberlite resin column was 80% less in the brain 30 min after DDC. The exhalation of 14CO2 was depressed by 80% in the first hour after DDC. When 14C-tyrosine was given 3.5 h after DDC the only differences between experimental and control rats were the increased incorporation of 14C into the glutamine-glutamate and aspartate fractions and the increased exhalation of 14CO2 which became significiant in the third and fourth half hour periods after the injection of 14C-tyrosine. From the experiments it is concluded that DDC, an inhibitor of dopamine-beta-hydroxylase, also interferes with the major catabolic pathway of tyrosine."} {"id": "PMID:181688", "title": "Interaction of digitoxigenin with lecithin membranes.", "content": "The binding of digitoxigenin to lecithin model membranes was investigated by application of electron spin- and nuclear magnetic resonance methods. A digitoxigenin spin-label derivative was found to bind specifically to the pseudohexagonal rigid lattice of lecithin membranes. The binding is accomplished by some of the structural features which are required for the biological activity of cardiac glycosides. Digitoxigenin has a procooperative effect on dipalmitoyl-lecithin membranes. The induction of lipid phase separation is discussed as a hypothetic molecular mechanism of action of cardiac glycosides on biological membranes.", "contents": "Interaction of digitoxigenin with lecithin membranes. The binding of digitoxigenin to lecithin model membranes was investigated by application of electron spin- and nuclear magnetic resonance methods. A digitoxigenin spin-label derivative was found to bind specifically to the pseudohexagonal rigid lattice of lecithin membranes. The binding is accomplished by some of the structural features which are required for the biological activity of cardiac glycosides. Digitoxigenin has a procooperative effect on dipalmitoyl-lecithin membranes. The induction of lipid phase separation is discussed as a hypothetic molecular mechanism of action of cardiac glycosides on biological membranes."} {"id": "PMID:181689", "title": "Effects of dopaminergic stimulants on cyclic nucleotide levels in mouse brain in vivo.", "content": "Dopaminergic stimulants (amantadine, amphetamine, apomorphine, nomifensine and L-dopa plus benserazide) increased cyclic GMP levels in the medial forebrain and cerebellum of mice. Cyclic AMP levels were not significantly altered under these conditions. Drug-induced stereotyped behaviour correlated in intensity and duration to the changes in cyclic GMP levels in the medial forebrain. Amantadine, apomorphine and nomifensine showed a linear dose response relationship, but differed as to the extent and time course of the increase in cyclic GMP. Amantadine and apomorphine were were more effective in elevating cyclic GMP in the medial forebrain than in the cerebellum. Amphetamine produced an exponential dose-related elevation of cyclic GMP in both parts of the brain, being more effective in the cerebellum than in the medial forebrain at high doses, thus indicating a complex mechanism of action. L-Dopa (50 mg/kg) and benserazide (40 mg/kg) alone did neither significantly increase cyclic GMP levels nor induce stereotyped behaviour. However, in animals pretreated with benserazide (15 min prior to L-odopa) L-dopa produced a significant elevation of cyclic GMP and stereotyped behaviour.", "contents": "Effects of dopaminergic stimulants on cyclic nucleotide levels in mouse brain in vivo. Dopaminergic stimulants (amantadine, amphetamine, apomorphine, nomifensine and L-dopa plus benserazide) increased cyclic GMP levels in the medial forebrain and cerebellum of mice. Cyclic AMP levels were not significantly altered under these conditions. Drug-induced stereotyped behaviour correlated in intensity and duration to the changes in cyclic GMP levels in the medial forebrain. Amantadine, apomorphine and nomifensine showed a linear dose response relationship, but differed as to the extent and time course of the increase in cyclic GMP. Amantadine and apomorphine were were more effective in elevating cyclic GMP in the medial forebrain than in the cerebellum. Amphetamine produced an exponential dose-related elevation of cyclic GMP in both parts of the brain, being more effective in the cerebellum than in the medial forebrain at high doses, thus indicating a complex mechanism of action. L-Dopa (50 mg/kg) and benserazide (40 mg/kg) alone did neither significantly increase cyclic GMP levels nor induce stereotyped behaviour. However, in animals pretreated with benserazide (15 min prior to L-odopa) L-dopa produced a significant elevation of cyclic GMP and stereotyped behaviour."} {"id": "PMID:181690", "title": "[Corticofugal influences on the reticulospinal neurons of gigantocellular nucleus in cats].", "content": "Stimulation of the motor cortex evoked excitatory and inhibitory PSP in reticulospinal neurons of the cat gigantocellular nucleus. EPSP were recorded in 94.3% of the investigated neurons and IPSP in 5.7%. Analysis of the presynaptic pathways showed that 77.4% of EPSPs appeared through monosynaptic and 22.6% through polysynaptic corticoreticular connections. According to latency, duration and rise time all monosynaptic EPSP were divided into two groups (fast and slow). Obviously, fast EPSPs are generated by fast corticobulbar fibres and slow ones by slow fibres. IPSP were recorded in neurons which were also inhibited by stimulation of the ventral funiculi of the spinal cord. It is suggested that motor cortical signals can be transmitted to the spinal cord through both mono- and polysynaptic connections of the fast and slow pyramidal neurons with reticulospinal neurons.", "contents": "[Corticofugal influences on the reticulospinal neurons of gigantocellular nucleus in cats]. Stimulation of the motor cortex evoked excitatory and inhibitory PSP in reticulospinal neurons of the cat gigantocellular nucleus. EPSP were recorded in 94.3% of the investigated neurons and IPSP in 5.7%. Analysis of the presynaptic pathways showed that 77.4% of EPSPs appeared through monosynaptic and 22.6% through polysynaptic corticoreticular connections. According to latency, duration and rise time all monosynaptic EPSP were divided into two groups (fast and slow). Obviously, fast EPSPs are generated by fast corticobulbar fibres and slow ones by slow fibres. IPSP were recorded in neurons which were also inhibited by stimulation of the ventral funiculi of the spinal cord. It is suggested that motor cortical signals can be transmitted to the spinal cord through both mono- and polysynaptic connections of the fast and slow pyramidal neurons with reticulospinal neurons."} {"id": "PMID:181692", "title": "Studies with bromocriptine: III. Concomitant administration of caffeine to patients with idiopathic parkinsonism.", "content": "Caffeine was administered to six patients with idiopathic parkinsonism in an attempt to potentiate the therapeutic response of bromocriptine, a dopamine (DA) receptor agonist, by inhibition of phosphodiesterase. In a double-blind study at doses of 1,000 mg daily, caffeine failed to enhance the antiparkinsonian action of bromocriptine (40 mg daily) given concomitantly. Although effective in potentiating the action of levodopa and other agonists in animal models of parkinsonism, caffeine is inactive in parkinsonism in man.", "contents": "Studies with bromocriptine: III. Concomitant administration of caffeine to patients with idiopathic parkinsonism. Caffeine was administered to six patients with idiopathic parkinsonism in an attempt to potentiate the therapeutic response of bromocriptine, a dopamine (DA) receptor agonist, by inhibition of phosphodiesterase. In a double-blind study at doses of 1,000 mg daily, caffeine failed to enhance the antiparkinsonian action of bromocriptine (40 mg daily) given concomitantly. Although effective in potentiating the action of levodopa and other agonists in animal models of parkinsonism, caffeine is inactive in parkinsonism in man."} {"id": "PMID:181693", "title": "Viruslike particles in granulomatous angiitis of the central nervous system.", "content": "Neuropathologic examination of the brain of a 67-year-old woman with a 5-month history of progressive multiple neurologic deficits showed granulomatous angiitis of the small parenchymal and leptomeningeal blood vessels of the brain and spinal cord. Electron microscopy of formalin-fixed brain disclosed intranuclear viruslike particles resembling herpesvirus. Although definitive proof cannot be established without further virologic tests, this previously unreported finding suggests that some cases of granulomatous angiitis of the central nervous system may result from viral infection.", "contents": "Viruslike particles in granulomatous angiitis of the central nervous system. Neuropathologic examination of the brain of a 67-year-old woman with a 5-month history of progressive multiple neurologic deficits showed granulomatous angiitis of the small parenchymal and leptomeningeal blood vessels of the brain and spinal cord. Electron microscopy of formalin-fixed brain disclosed intranuclear viruslike particles resembling herpesvirus. Although definitive proof cannot be established without further virologic tests, this previously unreported finding suggests that some cases of granulomatous angiitis of the central nervous system may result from viral infection."} {"id": "PMID:181695", "title": "Experimental myasthenia due to alpha-bungarotoxin.", "content": "Neuromuscular transmission was studied electrophysiologically in rabbits intoxicated by alpha-bungarotoxin, a specific inhibitor of acetylcholine receptor. The findings consisted of a slight reduction in amplitude of single evoked muscle action potentials, a decrement in amplitude of successive evoked muscle action potentials post-tetanic potentiation and exhaustion, edrophonium reversal, and no change of muscle action potentials evoked by direct stimulation of the muscle. These were similar to characteristic electrophysiologic phenomena seen in 40 patients with myasthenia gravis. The receptor abnormality may be responsible for the underlying defect of myasthenia.", "contents": "Experimental myasthenia due to alpha-bungarotoxin. Neuromuscular transmission was studied electrophysiologically in rabbits intoxicated by alpha-bungarotoxin, a specific inhibitor of acetylcholine receptor. The findings consisted of a slight reduction in amplitude of single evoked muscle action potentials, a decrement in amplitude of successive evoked muscle action potentials post-tetanic potentiation and exhaustion, edrophonium reversal, and no change of muscle action potentials evoked by direct stimulation of the muscle. These were similar to characteristic electrophysiologic phenomena seen in 40 patients with myasthenia gravis. The receptor abnormality may be responsible for the underlying defect of myasthenia."} {"id": "PMID:181696", "title": "Hyperthyroidism and myasthenia gravis with features of Eaton-Lambert syndrome.", "content": "In a 50-year-old man with hyperthyroidism and myasthenic weakness electrophysiologic phenomena similar to Eaton-Lambert syndrome were seen in classical myasthenia gravis. The orbicularis oculi showed an abnormally small muscle action potential in response to nerve stimulus and unusual facilitation of the response with activity. These signs are compatible with Eaton-Lambert syndrome, but the findings obtained from the adductor pollicis were typical of classical myasthenia. A possible common basis for hyperthyroidism and such an electrophysiologic complexity of transmission failure was considered as a pathogenic hypothesis.", "contents": "Hyperthyroidism and myasthenia gravis with features of Eaton-Lambert syndrome. In a 50-year-old man with hyperthyroidism and myasthenic weakness electrophysiologic phenomena similar to Eaton-Lambert syndrome were seen in classical myasthenia gravis. The orbicularis oculi showed an abnormally small muscle action potential in response to nerve stimulus and unusual facilitation of the response with activity. These signs are compatible with Eaton-Lambert syndrome, but the findings obtained from the adductor pollicis were typical of classical myasthenia. A possible common basis for hyperthyroidism and such an electrophysiologic complexity of transmission failure was considered as a pathogenic hypothesis."} {"id": "PMID:181697", "title": "Some metabolic effects of prolonged feeding of starch, sucrose, fructose and carbohydrate-free diet in the rat.", "content": "Male rats of the ASL Wistar strain were fed from weaning on starch, fructose or carbohydrate-free diets for 4 and 12 weeks. In addition, further groups were fed for 24 weeks on starch, sucrose or carbohydrate-free diets. Livers were examined for gross composition, glucose-6-phosphatase activity and in vitro lipogenesis and glucose oxidation. Intestinal sucrase was also measured. Dietary fructose and the carbohydrate-free diet induced an enlargement of the livers after 12 weeks feeding, when expressed per 100g body weight, and at the same time, an increased fat content. Fructose caused an increase in liver glucose-6-phosphatase after 4 weeks, which persisted after 12 weeks, and a similar increase was observed after 24 weeks feeding on sucrose. Fructose produced an increase in intestinal sucrose after 4 weeks, but this did not persist and there was no increase evident after 12 weeks feeding, nor after 24 weeks feeding on sucrose. Fructose markedly depressed the in vitro lipogenesis and glucose oxidation in liver slices. This was evident after 4 weeks feeding and also after 12 weeks when the effect of age showed as a fall in both these parameters in the control group of animals. The carbohydrate-free diet caused an increase in liver glucose-6-phosphatase after 4 weeks, a smaller increase after 12 weeks, and there was no increase apparent when feeding was continued for 24 weeks. Apparently due to the absence of substrate, the intestinal sucrose activity fell to less than half after 4 weeks and to negligible levels after 12 and 24 weeks on carbohydrate-free diet. In vitro liver lipogenesis and glucose oxidation were depressed after 4 and 12 weeks in a similar way to the fructose diet. On both these diets the rise in liver glucose-6-phosphatase appeared to parallel the fall in liver lipogeneis and glucose oxidation.", "contents": "Some metabolic effects of prolonged feeding of starch, sucrose, fructose and carbohydrate-free diet in the rat. Male rats of the ASL Wistar strain were fed from weaning on starch, fructose or carbohydrate-free diets for 4 and 12 weeks. In addition, further groups were fed for 24 weeks on starch, sucrose or carbohydrate-free diets. Livers were examined for gross composition, glucose-6-phosphatase activity and in vitro lipogenesis and glucose oxidation. Intestinal sucrase was also measured. Dietary fructose and the carbohydrate-free diet induced an enlargement of the livers after 12 weeks feeding, when expressed per 100g body weight, and at the same time, an increased fat content. Fructose caused an increase in liver glucose-6-phosphatase after 4 weeks, which persisted after 12 weeks, and a similar increase was observed after 24 weeks feeding on sucrose. Fructose produced an increase in intestinal sucrose after 4 weeks, but this did not persist and there was no increase evident after 12 weeks feeding, nor after 24 weeks feeding on sucrose. Fructose markedly depressed the in vitro lipogenesis and glucose oxidation in liver slices. This was evident after 4 weeks feeding and also after 12 weeks when the effect of age showed as a fall in both these parameters in the control group of animals. The carbohydrate-free diet caused an increase in liver glucose-6-phosphatase after 4 weeks, a smaller increase after 12 weeks, and there was no increase apparent when feeding was continued for 24 weeks. Apparently due to the absence of substrate, the intestinal sucrose activity fell to less than half after 4 weeks and to negligible levels after 12 and 24 weeks on carbohydrate-free diet. In vitro liver lipogenesis and glucose oxidation were depressed after 4 and 12 weeks in a similar way to the fructose diet. On both these diets the rise in liver glucose-6-phosphatase appeared to parallel the fall in liver lipogeneis and glucose oxidation."} {"id": "PMID:181701", "title": "Mass screening for breast disease. Results, problems, and expectations.", "content": "The first 18 months' experience of the Breast Diagnostic Center of Jefferson Medical College have been reviewed. Almost 14,000 patients were screened for breast disease, using a combination of clinical examination. Xeroradiography, and thermography. In this group of 14,000 women, 106 cases of cancer were discovered, in incidence of almost 8 per 1000 women screened. Of these 106 cases of cancer, 45.3% were clinically occult or not recognized by clinical examination, and within this group at the time of mastectomy only a small percent had any evidence of axillary lymph node metastases. The combination of several technics of examination is proving to be more reliable for the early detection of breast cancer than any of the technics alone, and programs such as these may make a significant difference in the death rate from breast cancer.", "contents": "Mass screening for breast disease. Results, problems, and expectations. The first 18 months' experience of the Breast Diagnostic Center of Jefferson Medical College have been reviewed. Almost 14,000 patients were screened for breast disease, using a combination of clinical examination. Xeroradiography, and thermography. In this group of 14,000 women, 106 cases of cancer were discovered, in incidence of almost 8 per 1000 women screened. Of these 106 cases of cancer, 45.3% were clinically occult or not recognized by clinical examination, and within this group at the time of mastectomy only a small percent had any evidence of axillary lymph node metastases. The combination of several technics of examination is proving to be more reliable for the early detection of breast cancer than any of the technics alone, and programs such as these may make a significant difference in the death rate from breast cancer."} {"id": "PMID:181703", "title": "Surveillance of hydatidiform mole with the Milan-Markley helix.", "content": "A case of complicated trophoblastic disease followed by quantitative radioimmunoassay and endometrial cytology is presented. Despite the fall of the postevacuation hCG titer to zero, trophoblastic elements were still detected cytologically with the helix technic. A second curettage performed 60 days postevacuation because of a rising serum hCG titer and persistent trophoblastic elements on the endometrial smears was histologically negative. Subsequent helix cytologic studies continued to reveal trophoblastic cells. Chemotherapy with methotrexate and hysterectomy were carried out. A solitary 7-mm lesion was found deep in the myometrium. Titers dropped abruptly postoperatively. Photomicrographs of the cytologic findings are presented.", "contents": "Surveillance of hydatidiform mole with the Milan-Markley helix. A case of complicated trophoblastic disease followed by quantitative radioimmunoassay and endometrial cytology is presented. Despite the fall of the postevacuation hCG titer to zero, trophoblastic elements were still detected cytologically with the helix technic. A second curettage performed 60 days postevacuation because of a rising serum hCG titer and persistent trophoblastic elements on the endometrial smears was histologically negative. Subsequent helix cytologic studies continued to reveal trophoblastic cells. Chemotherapy with methotrexate and hysterectomy were carried out. A solitary 7-mm lesion was found deep in the myometrium. Titers dropped abruptly postoperatively. Photomicrographs of the cytologic findings are presented."} {"id": "PMID:181702", "title": "Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms.", "content": "Fifteen patients with nonmetastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor. Complete and sustained remission was achieved in 14 of the 15 patients. Response to treatment was determined solely on the basis of serial serum human chorionic gonadotropin levels as measured by the beta subunit radioimmunoassay. All patients developed nonmetastatic gestational trophoblastic neoplasms following evacuation of a molar pregnancy. The known histologic diagnosis in all cases was hydatidiform mole. No significant toxicity was encountered despite careful monitoring of marrow, hepatic, renal, neurologic, and mucocutaneous parameters. Up to January 31, 1976, duration of remission ranged from 2 to 14 months.", "contents": "Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms. Fifteen patients with nonmetastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor. Complete and sustained remission was achieved in 14 of the 15 patients. Response to treatment was determined solely on the basis of serial serum human chorionic gonadotropin levels as measured by the beta subunit radioimmunoassay. All patients developed nonmetastatic gestational trophoblastic neoplasms following evacuation of a molar pregnancy. The known histologic diagnosis in all cases was hydatidiform mole. No significant toxicity was encountered despite careful monitoring of marrow, hepatic, renal, neurologic, and mucocutaneous parameters. Up to January 31, 1976, duration of remission ranged from 2 to 14 months."} {"id": "PMID:181715", "title": "[Absorption of testosterone-7 alpha-3H by tissues of organ-targets in male rat embryos].", "content": "The dynamics of consumption of testosterone-7alpha-3H by different tissues of the differentiating reproductive system, as well as by suprarenals, brain, hypothalamus and muscles was studied in the in vivo experiments with the rat male embryos beginning from the 14th and till the 20th days of development. The specific consumption of the labelled androgen related to the metabolic processes was observed at all developmental stages under study. The selective consumption of testosterone-7alpha-3H was noted prior to the beginning and during the morphogenesis of the organs-targets' rudiments. The radioactivity in tissues increased already 1--2 days following the castration of 18 days old embryos. Estrone, testosterone, testosterone-propionate, cyproterone-acetate competitively decreased the consumption of testosterone-7alpha-3H. The problem of reception of tissues of the rat male embryos to the male sex hormone is discussed.", "contents": "[Absorption of testosterone-7 alpha-3H by tissues of organ-targets in male rat embryos]. The dynamics of consumption of testosterone-7alpha-3H by different tissues of the differentiating reproductive system, as well as by suprarenals, brain, hypothalamus and muscles was studied in the in vivo experiments with the rat male embryos beginning from the 14th and till the 20th days of development. The specific consumption of the labelled androgen related to the metabolic processes was observed at all developmental stages under study. The selective consumption of testosterone-7alpha-3H was noted prior to the beginning and during the morphogenesis of the organs-targets' rudiments. The radioactivity in tissues increased already 1--2 days following the castration of 18 days old embryos. Estrone, testosterone, testosterone-propionate, cyproterone-acetate competitively decreased the consumption of testosterone-7alpha-3H. The problem of reception of tissues of the rat male embryos to the male sex hormone is discussed."} {"id": "PMID:181718", "title": "[Sensitivity and specificity of the passive hemagglutination reaction applied to titration of herpes antibodies].", "content": "52 human sera were checked for herpes virus hominis type 1 antibodies by passive hemagglutination, complement fixation, neutralization tests and plaque reduction in presence of complement. A good correlation was observed among the results obtained by the passive hemagglutination test and the plaque reduction in presence of complement. The rapidity of the indirect hemagglutination test and the sensitivity of the reaction are in favour of its routine use.", "contents": "[Sensitivity and specificity of the passive hemagglutination reaction applied to titration of herpes antibodies]. 52 human sera were checked for herpes virus hominis type 1 antibodies by passive hemagglutination, complement fixation, neutralization tests and plaque reduction in presence of complement. A good correlation was observed among the results obtained by the passive hemagglutination test and the plaque reduction in presence of complement. The rapidity of the indirect hemagglutination test and the sensitivity of the reaction are in favour of its routine use."} {"id": "PMID:181719", "title": "[Structural and biochemical alterations of human diabetic dermis studied by H-lysine incorporation and microscopy].", "content": "The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3H-lysine for four hours. The 3H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed ultrastructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. Fibroblasts contained an increased amount of electron dense deposits in the cytoplasm and dilated endoplasmic reticulum. The collagen bundles were dissociated. Elastic fibers under the epithelial basal laminae were fragmented or absent. The incorporation pattern of 3H-lysine into these macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl2 extractable fraction an in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement.", "contents": "[Structural and biochemical alterations of human diabetic dermis studied by H-lysine incorporation and microscopy]. The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3H-lysine for four hours. The 3H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed ultrastructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. Fibroblasts contained an increased amount of electron dense deposits in the cytoplasm and dilated endoplasmic reticulum. The collagen bundles were dissociated. Elastic fibers under the epithelial basal laminae were fragmented or absent. The incorporation pattern of 3H-lysine into these macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl2 extractable fraction an in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement."} {"id": "PMID:181720", "title": "[Relation between urinary cyclic AMP, PTH and histomorphometric resorption parameter. A study of 44 human iliac crest bone biopsies].", "content": "Daily urinary cyclic AMP (AMPcU) has been compared to pth plasma level and to bone resorption parameters in 44 cases of metabolic bone disease. In 14 cases of primary hyperparathyroidism, AMPcU was always increased likewise in 4 cases of osteomalacia with secondary hyperparathyroidism. On the whole series of cases a significant correlation has been found (1) between PTH plasma level and AMPcU and (2) between bone resporption surfaces and AMPcU. Conversely, no correlation between PTH and periosteocytic lacunae size, nor between AMPcU and periosteocytic lacunae has been found.", "contents": "[Relation between urinary cyclic AMP, PTH and histomorphometric resorption parameter. A study of 44 human iliac crest bone biopsies]. Daily urinary cyclic AMP (AMPcU) has been compared to pth plasma level and to bone resorption parameters in 44 cases of metabolic bone disease. In 14 cases of primary hyperparathyroidism, AMPcU was always increased likewise in 4 cases of osteomalacia with secondary hyperparathyroidism. On the whole series of cases a significant correlation has been found (1) between PTH plasma level and AMPcU and (2) between bone resporption surfaces and AMPcU. Conversely, no correlation between PTH and periosteocytic lacunae size, nor between AMPcU and periosteocytic lacunae has been found."} {"id": "PMID:181717", "title": "[Histochemical study of the cysticercoids of cestodes of the genus Aploparaksis Clerc, 1903 (Hymenolepididae)].", "content": "Hystochemical methods were employed in order to study the distribution of succinic dehydrogenase, glucose-6-phosphate-dehydrogenase, alcaline, acidic phosphatases, lipids, fatty acids, glycogen and neutral. mucopolysaccharides in larvae of three species of cestodes: A. birulai, A. polystictae, A. xemae. A high concentration of succinic dehydrogenase was recorded from the tissue of the tail, scolex and neck. Glycose-6-phosphatdehydrogenase was found in great quantity only in the external parenchyma of the neck of A. polystictae. Here accumulations were observed of lipids which apparently are the products of excretion. The glycogen localization coincides with the distribution of succinis dehydrogenase. The activity of phosphatases is concentration in the structures of the tail and external membranes of cysticercoids, the acidic phosphatase being dominant. It was concluded that aerobic oxidation dominates in larvae and substances are principally transported through the tail area and excretory aperture.", "contents": "[Histochemical study of the cysticercoids of cestodes of the genus Aploparaksis Clerc, 1903 (Hymenolepididae)]. Hystochemical methods were employed in order to study the distribution of succinic dehydrogenase, glucose-6-phosphate-dehydrogenase, alcaline, acidic phosphatases, lipids, fatty acids, glycogen and neutral. mucopolysaccharides in larvae of three species of cestodes: A. birulai, A. polystictae, A. xemae. A high concentration of succinic dehydrogenase was recorded from the tissue of the tail, scolex and neck. Glycose-6-phosphatdehydrogenase was found in great quantity only in the external parenchyma of the neck of A. polystictae. Here accumulations were observed of lipids which apparently are the products of excretion. The glycogen localization coincides with the distribution of succinis dehydrogenase. The activity of phosphatases is concentration in the structures of the tail and external membranes of cysticercoids, the acidic phosphatase being dominant. It was concluded that aerobic oxidation dominates in larvae and substances are principally transported through the tail area and excretory aperture."} {"id": "PMID:181724", "title": "Fetal lung maturation IV: the release of phosphatidic acid phosphohydrolase and phospholipids into the human amniotic fluid.", "content": "The relationship between surface active material and phosphatidic acid phosphohydrolase (PAPase) activity was examined in human amniotic fluid after centrifugation at 105,000 X g for one hour. The distribution of PAPase activity between the pellet and supernatant fractions was similar to that of phospholipids in the amniotic fluid. The majority of the PAPase activity was found to be associated with the pellet fraction. Similarly, 82% of the phospholipid was also present in this fraction. Of the total palmitate present in the original sample, approximately 90% was found in the pellet after centrifugation. Palmitic acid constituted 75% of all fatty acids present in the phosphatidylcholine identified in the pellet. By sharp contrast only 4% of the total protein was pelletized by centrifugation. The pelletized fraction isolated from amniotic fluid after 105,000 X g centrifugation closely resembles the lamellar bodies in: (1) its phospholipid pattern; (2) palmitate concentration in phosphatidylcholine; and, (3) the presence of PAPase activity with a high specific activity. Collectively, these findings lend strong support to the concept that a lamellar-like body is released from fetal lung into the amniotic fluid.", "contents": "Fetal lung maturation IV: the release of phosphatidic acid phosphohydrolase and phospholipids into the human amniotic fluid. The relationship between surface active material and phosphatidic acid phosphohydrolase (PAPase) activity was examined in human amniotic fluid after centrifugation at 105,000 X g for one hour. The distribution of PAPase activity between the pellet and supernatant fractions was similar to that of phospholipids in the amniotic fluid. The majority of the PAPase activity was found to be associated with the pellet fraction. Similarly, 82% of the phospholipid was also present in this fraction. Of the total palmitate present in the original sample, approximately 90% was found in the pellet after centrifugation. Palmitic acid constituted 75% of all fatty acids present in the phosphatidylcholine identified in the pellet. By sharp contrast only 4% of the total protein was pelletized by centrifugation. The pelletized fraction isolated from amniotic fluid after 105,000 X g centrifugation closely resembles the lamellar bodies in: (1) its phospholipid pattern; (2) palmitate concentration in phosphatidylcholine; and, (3) the presence of PAPase activity with a high specific activity. Collectively, these findings lend strong support to the concept that a lamellar-like body is released from fetal lung into the amniotic fluid."} {"id": "PMID:181725", "title": "Vitamin D: the discovery of its metabolites and their therapeutic applications.", "content": "Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated. The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1alpha-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds.", "contents": "Vitamin D: the discovery of its metabolites and their therapeutic applications. Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated. The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1alpha-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds."} {"id": "PMID:181726", "title": "Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids.", "content": "A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia.", "contents": "Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids. A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia."} {"id": "PMID:181730", "title": "The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase.", "content": "Vitamin C breaks DNA only in the presence of oxygen. Superoxide dismutase has no effect on the reaction but catalase suppresses it. Superoxide also gives rise to breaks in DNA suppressible by both superoxide dismutase and catalase. The hydroxyl radical seems to be the agent responsible for strand cleavage itself.", "contents": "The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase. Vitamin C breaks DNA only in the presence of oxygen. Superoxide dismutase has no effect on the reaction but catalase suppresses it. Superoxide also gives rise to breaks in DNA suppressible by both superoxide dismutase and catalase. The hydroxyl radical seems to be the agent responsible for strand cleavage itself."} {"id": "PMID:181731", "title": "Isolation and characterization of poly(A)-containing intranuclear polyoma-specific \"giant\" RNA'S.", "content": "Heterogeneous polyoma giant RNA molecules have been isolated by oligo(dT)- cellulose chromatography during the late phase of a lytic cycle of infection of mouse kidney cell cultures. These RNAs have sedimentation coefficients in denaturing Me2SO gradients that are greater than 26S and thus apparently correspond to RNA molecules larger than one strand of polyoma DNA. Approximately 15% of total nuclear polyoma late giant RNAs contained tracts of poly(A) and were retained by oligo(dT)-cellulose. The polyoma late giant RNAs as well as heterogeneous nuclear RNAs (HnRNAs) were found to have a slightly lower sedimentation rate in Me2SO-chloral hydrate density gradients than sedimentation values in sucrose gradients indicated. Even when synthesis of viral DNA and the production of capsid protein are blocked by 5-fluorodeoxyuridine (FdU), 10% of polyoma-specific RNA (as determined by sedimentation analyses under aqueous conditions) was shown to contain tracts of poly(A). In contrast to our findings on polyoma late giant RNA, nuclear polyoma RNA synthesized in the presence of FdU sedimented in denaturing Me2SO-chloral hydrate gradients considerably slower (from 15 to 30S) in relation to HnRNA and ribosomal precursor RNA. The sedimentation pattern in denaturing Me2SO gradients suggest that Py RNA synthesized late in lytic infection in the presence of FdU may be no longer than one transcript of Py DNA.", "contents": "Isolation and characterization of poly(A)-containing intranuclear polyoma-specific \"giant\" RNA'S. Heterogeneous polyoma giant RNA molecules have been isolated by oligo(dT)- cellulose chromatography during the late phase of a lytic cycle of infection of mouse kidney cell cultures. These RNAs have sedimentation coefficients in denaturing Me2SO gradients that are greater than 26S and thus apparently correspond to RNA molecules larger than one strand of polyoma DNA. Approximately 15% of total nuclear polyoma late giant RNAs contained tracts of poly(A) and were retained by oligo(dT)-cellulose. The polyoma late giant RNAs as well as heterogeneous nuclear RNAs (HnRNAs) were found to have a slightly lower sedimentation rate in Me2SO-chloral hydrate density gradients than sedimentation values in sucrose gradients indicated. Even when synthesis of viral DNA and the production of capsid protein are blocked by 5-fluorodeoxyuridine (FdU), 10% of polyoma-specific RNA (as determined by sedimentation analyses under aqueous conditions) was shown to contain tracts of poly(A). In contrast to our findings on polyoma late giant RNA, nuclear polyoma RNA synthesized in the presence of FdU sedimented in denaturing Me2SO-chloral hydrate gradients considerably slower (from 15 to 30S) in relation to HnRNA and ribosomal precursor RNA. The sedimentation pattern in denaturing Me2SO gradients suggest that Py RNA synthesized late in lytic infection in the presence of FdU may be no longer than one transcript of Py DNA."} {"id": "PMID:181737", "title": "Search for potential amoebicides. Part V. N-substituted 2-nitro-4,5-dimethoxybenzamides and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids.", "content": "The authors in all have synthesised 28 new N-substituted 2-nitro, 4,5-dimethoxy-benzamides, and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids with a view to obtain potent amoebicides. Their work is based on the observation that a large number of dimethoxyphenyl substituted derivatives occupy an important place as antiamobic agents. Fourteen belonging to different series subjected to in vitro screening for amoebicidal activity against E. histolytica failed to show any significant activity.", "contents": "Search for potential amoebicides. Part V. N-substituted 2-nitro-4,5-dimethoxybenzamides and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids. The authors in all have synthesised 28 new N-substituted 2-nitro, 4,5-dimethoxy-benzamides, and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids with a view to obtain potent amoebicides. Their work is based on the observation that a large number of dimethoxyphenyl substituted derivatives occupy an important place as antiamobic agents. Fourteen belonging to different series subjected to in vitro screening for amoebicidal activity against E. histolytica failed to show any significant activity."} {"id": "PMID:181739", "title": "Studies on the relationship between intestinal flora and cecal coccidiosis in chicken.", "content": "The bacteriological and histopathological changes in the ceca of young chickens after being infected with sporulated oocysts of Eimeria tenella were investigated. Lactobacilli and bifidobacteria showed remarkable decrease in number on the 5th day after infection, when shizont and gametocyate came to appear, and destruction of mucosa along with severe haemorrhaging was noticed. Other predominant bacteria like bacteroidaceae, catenabacteria and peptostreptococci showed only moderate and temporal decrease in number during the infection. Clostridium perfringens prolifereated after the 5th day post infection following the decline of lactobacilli and bifidobacteria. Proliferation of clostridia was so intense that the number was almost million times greater than that of the uninfected chicken at its peak on the 7th day after infection. Enterobacteria also showed a moderate but persistent increase in number. Most bacteria came to the normal population on the 10th day after infection. As for lactobacilli, bifidobacteria, clostridia and enterobacteria, the disturbances were still noticeable on the 17th day after injection. Antagonism between proliferated bacteria (clostridia and enterobacteria) and lactic acid bacteria (lactobacilli and bifidobacteria) whose intensity is suppose to be related to the cecal mucosa is suggested during cecal coccidiosis in chickens.", "contents": "Studies on the relationship between intestinal flora and cecal coccidiosis in chicken. The bacteriological and histopathological changes in the ceca of young chickens after being infected with sporulated oocysts of Eimeria tenella were investigated. Lactobacilli and bifidobacteria showed remarkable decrease in number on the 5th day after infection, when shizont and gametocyate came to appear, and destruction of mucosa along with severe haemorrhaging was noticed. Other predominant bacteria like bacteroidaceae, catenabacteria and peptostreptococci showed only moderate and temporal decrease in number during the infection. Clostridium perfringens prolifereated after the 5th day post infection following the decline of lactobacilli and bifidobacteria. Proliferation of clostridia was so intense that the number was almost million times greater than that of the uninfected chicken at its peak on the 7th day after infection. Enterobacteria also showed a moderate but persistent increase in number. Most bacteria came to the normal population on the 10th day after infection. As for lactobacilli, bifidobacteria, clostridia and enterobacteria, the disturbances were still noticeable on the 17th day after injection. Antagonism between proliferated bacteria (clostridia and enterobacteria) and lactic acid bacteria (lactobacilli and bifidobacteria) whose intensity is suppose to be related to the cecal mucosa is suggested during cecal coccidiosis in chickens."} {"id": "PMID:181740", "title": "Variant infectious bronchitis virus isolated from Indiana chickens.", "content": "Infectious bronchitis virus (IBV) associated with a catarrhal tracheitis, sudden decline in egg production, and reduced shell quality was isolated from an Indiana White Leghorn breeder flock. It was found to be serologically different from Massachusetts, Connecticut, Iowa 97, Iowa 609, Florida, Arkansas 99, JMK, Holte, Gray and SE 17 IBV serotypes. Two different Massachusetts vaccine strains protected chickens from respiratory signs but not against virus infection using the isolant for challenge in laboratory trials. The isolant was passed through a 0.22 mu. filter. It was heat (56 C), acid pH (3.0), ether and chloroform labile. In embryos it produced deaths or lesions of infectious bronchitis in one to five days after inoculation. It is suggested that this IBV isolant be designated Indiana-type.", "contents": "Variant infectious bronchitis virus isolated from Indiana chickens. Infectious bronchitis virus (IBV) associated with a catarrhal tracheitis, sudden decline in egg production, and reduced shell quality was isolated from an Indiana White Leghorn breeder flock. It was found to be serologically different from Massachusetts, Connecticut, Iowa 97, Iowa 609, Florida, Arkansas 99, JMK, Holte, Gray and SE 17 IBV serotypes. Two different Massachusetts vaccine strains protected chickens from respiratory signs but not against virus infection using the isolant for challenge in laboratory trials. The isolant was passed through a 0.22 mu. filter. It was heat (56 C), acid pH (3.0), ether and chloroform labile. In embryos it produced deaths or lesions of infectious bronchitis in one to five days after inoculation. It is suggested that this IBV isolant be designated Indiana-type."} {"id": "PMID:181741", "title": "Reduced symptoms of anaphylaxis in chickens by ACTH or heat.", "content": "Exogenous ACTH, when administered intramuscularly in four equal doses of 2 I.U./100 gm. of body weight at 24, 23, 22, and 21 hours prior to challenge with BSA, reduced the severity of anaphylaxis in BSA sensitized juvenile chickens. Additionally, a single heat exposure (45 degrees C.) of 30 minutes at 24 hours prior to challenge consistently reduced the severity of anaphylaxis. Single heating exposures at 24 hours prior to sensitization or at 48 hours prior to challenge did not influence the anaphylactic response. In one of two experiments single heat exposures at one hour prior to challenge reduced the severity of anaphylaxis. The levels of anti-BSA antibody which existed immediately prior to challenge were not affected by the heat treatments. These data demonstrate clearly that exogenous ACTH and a single, non-lethal heating episode, when applied 24 hours prior to the induction of anaphylaxis, reduced the severity of the symptoms associated with this particular hypersensitive reaction in the domestic chicken.", "contents": "Reduced symptoms of anaphylaxis in chickens by ACTH or heat. Exogenous ACTH, when administered intramuscularly in four equal doses of 2 I.U./100 gm. of body weight at 24, 23, 22, and 21 hours prior to challenge with BSA, reduced the severity of anaphylaxis in BSA sensitized juvenile chickens. Additionally, a single heat exposure (45 degrees C.) of 30 minutes at 24 hours prior to challenge consistently reduced the severity of anaphylaxis. Single heating exposures at 24 hours prior to sensitization or at 48 hours prior to challenge did not influence the anaphylactic response. In one of two experiments single heat exposures at one hour prior to challenge reduced the severity of anaphylaxis. The levels of anti-BSA antibody which existed immediately prior to challenge were not affected by the heat treatments. These data demonstrate clearly that exogenous ACTH and a single, non-lethal heating episode, when applied 24 hours prior to the induction of anaphylaxis, reduced the severity of the symptoms associated with this particular hypersensitive reaction in the domestic chicken."} {"id": "PMID:181742", "title": "The nature of the phosphorus linkage in component I, a phosphoprotein isolated from the blood serum of DES-treated cockerels.", "content": "The nature of the phosphorus linkage in electrophoretic component I of the blood serum of DES-treated cockerels was investigated by enzymatic and partial acid and alkali dephosphorylation. The C-P bond was excluded because this bond is stable to 6 N HCl at 110 degrees C. for 20 hours, and all the phosphorus was released under these conditions. No phosphorus was released when diesterase, pyrophosphatase and 0.25 N HCl were employed, and this excludes the diester, pyrophosphate and N-P bonds. The presence of the O-P bond was supported by the release of phosphate by the phosphatases and 0.25 N NaOH. The hydrolysate produced upon hydrolysis with pronase and papain contained phosphoserine. No phosphothreonine was present.", "contents": "The nature of the phosphorus linkage in component I, a phosphoprotein isolated from the blood serum of DES-treated cockerels. The nature of the phosphorus linkage in electrophoretic component I of the blood serum of DES-treated cockerels was investigated by enzymatic and partial acid and alkali dephosphorylation. The C-P bond was excluded because this bond is stable to 6 N HCl at 110 degrees C. for 20 hours, and all the phosphorus was released under these conditions. No phosphorus was released when diesterase, pyrophosphatase and 0.25 N HCl were employed, and this excludes the diester, pyrophosphate and N-P bonds. The presence of the O-P bond was supported by the release of phosphate by the phosphatases and 0.25 N NaOH. The hydrolysate produced upon hydrolysis with pronase and papain contained phosphoserine. No phosphothreonine was present."} {"id": "PMID:181746", "title": "Isolation and partial charcterization of a cytochrome b complex and cytochrome oxidase from yeast mitochondria.", "content": "A cytochrome b complex and cytochrome oxidase have been purified 14- and 20-fold respectively from yeast submitochondrial particles by a simple procedure involving their spontaneous precipitation from a deoxycholate extract. The recovery of both proteins was almost quantitative. The specific heme contents were 11 and 8 nmoles/mg protein for the cytochrome b complex and cytochrome oxidase respectively and both were spectrally pure. Sodium dodecyl sulfate gel electrophoresis resolved the cytochrome b complex into seven distinct subunits with molecular weights 42,000, 33,000, 27,500, 23,000, 15,500, 13,000 and 10,500. Cytochrome oxidase contained five bands with molecular weights 42,000, 26,500, 21,000, 14,000 and 10,500.", "contents": "Isolation and partial charcterization of a cytochrome b complex and cytochrome oxidase from yeast mitochondria. A cytochrome b complex and cytochrome oxidase have been purified 14- and 20-fold respectively from yeast submitochondrial particles by a simple procedure involving their spontaneous precipitation from a deoxycholate extract. The recovery of both proteins was almost quantitative. The specific heme contents were 11 and 8 nmoles/mg protein for the cytochrome b complex and cytochrome oxidase respectively and both were spectrally pure. Sodium dodecyl sulfate gel electrophoresis resolved the cytochrome b complex into seven distinct subunits with molecular weights 42,000, 33,000, 27,500, 23,000, 15,500, 13,000 and 10,500. Cytochrome oxidase contained five bands with molecular weights 42,000, 26,500, 21,000, 14,000 and 10,500."} {"id": "PMID:181747", "title": "A model for cytochrome oxidase.", "content": "A model is proposed for the active center of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in which cytochrome a is a low-spin ferrihemoprotein and cytochrome a3 is a high-spin ferrihemoprotein antiferromagnetically coupled to one of the two Cu2+ ions present in the enzyme. It is further proposed that reduction is accompanied by a conformational change in the enzyme thus exposing the sixth coordination site of cytochrome a3 to ligands. With this model it is possible to account for a variety of outstanding observations including the results of magnetic circular dichroism, Mossbauer, and electron paramagnetic resonance spectroscopies, as well as magnetic susceptibility measurements.", "contents": "A model for cytochrome oxidase. A model is proposed for the active center of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in which cytochrome a is a low-spin ferrihemoprotein and cytochrome a3 is a high-spin ferrihemoprotein antiferromagnetically coupled to one of the two Cu2+ ions present in the enzyme. It is further proposed that reduction is accompanied by a conformational change in the enzyme thus exposing the sixth coordination site of cytochrome a3 to ligands. With this model it is possible to account for a variety of outstanding observations including the results of magnetic circular dichroism, Mossbauer, and electron paramagnetic resonance spectroscopies, as well as magnetic susceptibility measurements."} {"id": "PMID:181748", "title": "Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses.", "content": "The amounts of unintegrated murine leukemia virus-specific DNA detected by molecular hybridization in extracts of Fv-ln/n (strains NIH/3T3, SIM) or Fv-lb/b (strains JLS-V9, SIM.R) mouse cells after infection with N- or B-tropic viruses were found to be the same in both permissive and resistant cells. Therefore, formation of DNA products from the viral RNA template does not appear to be grossly affected by the Fv-l gene product. Integration of virus-specific DNA into chromosomal cellular DNA was assayed by hybridization of radioactive complementary DNA to DNA from infected cells. With either NIH/3T3 or SIM.R cells infected with N- or B-tropic viruses, integration of proviral DNA could be detected in permissive cells but not in nonpermissive cells. The Fv-l gene product therefore appears to prevent integration of proviral DNA.", "contents": "Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses. The amounts of unintegrated murine leukemia virus-specific DNA detected by molecular hybridization in extracts of Fv-ln/n (strains NIH/3T3, SIM) or Fv-lb/b (strains JLS-V9, SIM.R) mouse cells after infection with N- or B-tropic viruses were found to be the same in both permissive and resistant cells. Therefore, formation of DNA products from the viral RNA template does not appear to be grossly affected by the Fv-l gene product. Integration of virus-specific DNA into chromosomal cellular DNA was assayed by hybridization of radioactive complementary DNA to DNA from infected cells. With either NIH/3T3 or SIM.R cells infected with N- or B-tropic viruses, integration of proviral DNA could be detected in permissive cells but not in nonpermissive cells. The Fv-l gene product therefore appears to prevent integration of proviral DNA."} {"id": "PMID:181749", "title": "Monomer molecular weight of T antigen from simian virus 40-infected and transformed cells.", "content": "T-antigens from simian virus 40 (SV 40)-transformed and lytically infected cells have been isolated by immunoprecipitation and their molecular weights estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T-antigen from SV40-transformed mouse and hamster cells has an apparent molecular weight of 94,000 whereas that from several lines of SV40-infected monkey cells is 84,000. In a wheat germ cell-free system, mRNA from either transformed or productively infected cells is translated into a 94,000 species. Experiments with the protease inhibitors L-l-(tosylamide-2-phenyl)ethylchloromethyl ketone HCl and N-alpha-p-tosyl-L-lysylchloromethyl ketone HCl suggest that the 84,000 species of T-antigen found in infected cells is derived from the larger species by proteolytic cleavage. Further, the cleavage pathway probably involves a two-step reaction with an 89,000 intermediate. The biological significance of the two molecular weight forms of T-antigen is unknown, but the possibility that they have different physiological activities is discussed.", "contents": "Monomer molecular weight of T antigen from simian virus 40-infected and transformed cells. T-antigens from simian virus 40 (SV 40)-transformed and lytically infected cells have been isolated by immunoprecipitation and their molecular weights estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T-antigen from SV40-transformed mouse and hamster cells has an apparent molecular weight of 94,000 whereas that from several lines of SV40-infected monkey cells is 84,000. In a wheat germ cell-free system, mRNA from either transformed or productively infected cells is translated into a 94,000 species. Experiments with the protease inhibitors L-l-(tosylamide-2-phenyl)ethylchloromethyl ketone HCl and N-alpha-p-tosyl-L-lysylchloromethyl ketone HCl suggest that the 84,000 species of T-antigen found in infected cells is derived from the larger species by proteolytic cleavage. Further, the cleavage pathway probably involves a two-step reaction with an 89,000 intermediate. The biological significance of the two molecular weight forms of T-antigen is unknown, but the possibility that they have different physiological activities is discussed."} {"id": "PMID:181750", "title": "Independent regulation of endogenous and exogenous avian RNA tumor virus genes.", "content": "3H-Labeled complementary DNA specific for the envelope glycoprotein (env) gene of avian leukosis-sarcoma viruses was isolated by selective nucleic acid hybridization techniques, and used to analyze the expression of the endogenous provirus. The endogenous provirus in certain cell types termed chicken helper factor positive (chf+) can synthesize the envelope glycoprotein. Env DNA sequences were present in both chf+ and chf- cells, but env RNA was detectable only in positive cell types. When these cells were infected with the Bryan strain of Rous sarcoma virus (BH-RSV), a defective virus which is deleted in the env gene, the levels of endogenous env RNA remained unchanged, although exogenous BH-RSV specific RNA was synthesized in very high amounts. Thus, the infecting virus did not appear to influence the expression of the endogenous virus. Likewise, the endogenous virus did not influence the exogenous virus expression, since similar amounts of BH-RSV specific RNA were present in all infected cell types, regardless of the level of endogenous virus expression.", "contents": "Independent regulation of endogenous and exogenous avian RNA tumor virus genes. 3H-Labeled complementary DNA specific for the envelope glycoprotein (env) gene of avian leukosis-sarcoma viruses was isolated by selective nucleic acid hybridization techniques, and used to analyze the expression of the endogenous provirus. The endogenous provirus in certain cell types termed chicken helper factor positive (chf+) can synthesize the envelope glycoprotein. Env DNA sequences were present in both chf+ and chf- cells, but env RNA was detectable only in positive cell types. When these cells were infected with the Bryan strain of Rous sarcoma virus (BH-RSV), a defective virus which is deleted in the env gene, the levels of endogenous env RNA remained unchanged, although exogenous BH-RSV specific RNA was synthesized in very high amounts. Thus, the infecting virus did not appear to influence the expression of the endogenous virus. Likewise, the endogenous virus did not influence the exogenous virus expression, since similar amounts of BH-RSV specific RNA were present in all infected cell types, regardless of the level of endogenous virus expression."} {"id": "PMID:181751", "title": "Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote.", "content": "Monolayers of normal human fibroblasts were observed to bind ferritin-labeled low density lipoprotein (LDL-ferritin) at specific receptor sites on the cell surface membrane. When fibroblasts were incubated with LDL-ferritin at 4 degrees, more than 70% of the surface-bound ferritin cores were localized by electron microscopy to short segments of the plasma membrane where the membrane appeared indented and coated on both of its sides by a fuzzy material. These membrane segments corresponded to \"coated regions\" previously described in other cell types. Unver the conditions of these experiments, an average of 55 LDL-ferritin particles were bound to each millimeter of plasma membrane in normal cells. In the presence of a 15-fold excess of native LDL, the number of bound ferritin cores was reduced by 75%, suggesting that the LDL-ferritin was binding to specific LDL receptor sites. Although fibroblasts from a patient with the homozygous form of familial hypercholesterolemia contained the same number of indented, coated membrane regions per millimeter of cell surface as did normal cells, no LDL-ferritin was observed to bind to the cell membrane in these mutant cells. The present ultrastructural data are consistent with previous biochemical and genetic evidence indicating that LDL exerts its regulatory action on cellular cholesterol metabolism in fibroblasts through an interaction with a specific cell surface receptor and that this receptor is defective in homozygous familial hypercholesterolemia fibroblasts. Moreover, the data suggest that the LDL receptor is localized to indented, coated regions of the plasma membrane that appear to participate in the adsorptive endocytosis of proteins.", "contents": "Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote. Monolayers of normal human fibroblasts were observed to bind ferritin-labeled low density lipoprotein (LDL-ferritin) at specific receptor sites on the cell surface membrane. When fibroblasts were incubated with LDL-ferritin at 4 degrees, more than 70% of the surface-bound ferritin cores were localized by electron microscopy to short segments of the plasma membrane where the membrane appeared indented and coated on both of its sides by a fuzzy material. These membrane segments corresponded to \"coated regions\" previously described in other cell types. Unver the conditions of these experiments, an average of 55 LDL-ferritin particles were bound to each millimeter of plasma membrane in normal cells. In the presence of a 15-fold excess of native LDL, the number of bound ferritin cores was reduced by 75%, suggesting that the LDL-ferritin was binding to specific LDL receptor sites. Although fibroblasts from a patient with the homozygous form of familial hypercholesterolemia contained the same number of indented, coated membrane regions per millimeter of cell surface as did normal cells, no LDL-ferritin was observed to bind to the cell membrane in these mutant cells. The present ultrastructural data are consistent with previous biochemical and genetic evidence indicating that LDL exerts its regulatory action on cellular cholesterol metabolism in fibroblasts through an interaction with a specific cell surface receptor and that this receptor is defective in homozygous familial hypercholesterolemia fibroblasts. Moreover, the data suggest that the LDL receptor is localized to indented, coated regions of the plasma membrane that appear to participate in the adsorptive endocytosis of proteins."} {"id": "PMID:181752", "title": "Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice.", "content": "AKR mice produce, from shortly after birth, high titers of their endogenous Gross type murine leukemia virus, and develop a thymus-derived leukemia at 7-9 months of age. We show that this oncogenesis is accompanied by an increase in the number of AKR-specific DNA sequences in the tumor tissues, whereas the \"non-target\" organs are not affected. Sequence increase was determined by kinetic analysis of DNA reassociation using an AKR-murine leukemia virus (MuLV)-specific cDNA and also by hybridization with excess AKR cDNA. The AKR cDNA was selected to recognize AKR sequences without significant crossreaction with DNA sequences of other endogenous viruses. The results show that during the development of the leukemia, the number of AKR-MuLV-specific genes increases in tumor tissues by a factor of 1 1/2 to 2.", "contents": "Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice. AKR mice produce, from shortly after birth, high titers of their endogenous Gross type murine leukemia virus, and develop a thymus-derived leukemia at 7-9 months of age. We show that this oncogenesis is accompanied by an increase in the number of AKR-specific DNA sequences in the tumor tissues, whereas the \"non-target\" organs are not affected. Sequence increase was determined by kinetic analysis of DNA reassociation using an AKR-murine leukemia virus (MuLV)-specific cDNA and also by hybridization with excess AKR cDNA. The AKR cDNA was selected to recognize AKR sequences without significant crossreaction with DNA sequences of other endogenous viruses. The results show that during the development of the leukemia, the number of AKR-MuLV-specific genes increases in tumor tissues by a factor of 1 1/2 to 2."} {"id": "PMID:181753", "title": "Natural antibodies in sera from healthy humans to antigens on surfaces of type C RNA viruses and cells from primates.", "content": "Sera from healthy humans contained naturally occurring antibody against group- or subgroup-specific antigen on the envelope of the following type C viruses isolated from primates: gibbon ape leukemia virus, simian (woolly monkey) sarcoma virus, baboon endogenous type C virus, and putative human type C viruses [HL23V isolated from blood cells of a patient with acute myelogenous leukemia (HL23) and HEL-12V from human embryonic diploid cells (CIH-32)]. Two sera also reacted with C57BL/6 mouse leukemia induced by Friend virus. These results were obtained by indirect immunoelectron microscopy with various virus-producing cells and by absorption tests using as targets gibbon lymphosarcoma cells that release gibbon ape leukemia virus. In a previous report, the presence of natural antibody in sera from healthy gibbon apes was demonstrated. When the specificities of the human and gibbon natural antibodies were compared, the human natural antibody reacted with two nonproducing culture cell lines of human lymphocytic leukemia (CEM-A and MOLT) and with human embryonic diploid (CIH-1(V-) cells [which became type C virus-producing CIH-32(V+) cells after many passages], but did not react with normal gibbon spleen monolayer cells. In contrast, gibbon natural antibody showed no reaction with CEM-A, MOLT, and CIH-1(V-) cells but reacted with gibbon spleen monolayer cells. Neither human nor gibbon natural antibody that was reactive with gibbon ape leukemia virus crossreacted with feline leukemia virus and mouse wild-type AKR leukemia virus. The gibbon lymphosarcoma cells releasing gibbon ape leukemia virus were used in a screening study of sera from healthy humans. Out of 72 sera screened by indirect immunoelectron microscopy using this system, 55 were positive (76%), i.e., 26 out of 35 males (74%) and 29 out of 37 females (78%). The highest incidence of antibody production was in 1- to 10-year-olds and 31- to 40-year-olds, with the adults exhibiting higher levels. Differences in incidence of natural antibody were not found to be sex-linked. These findings suggest that type C RNA viruses related to the gibbon ape leukemia virus and simian (woolly monkey) sarcoma virus family as well as the baboon endogenous type C virus family may be widespread in humans.", "contents": "Natural antibodies in sera from healthy humans to antigens on surfaces of type C RNA viruses and cells from primates. Sera from healthy humans contained naturally occurring antibody against group- or subgroup-specific antigen on the envelope of the following type C viruses isolated from primates: gibbon ape leukemia virus, simian (woolly monkey) sarcoma virus, baboon endogenous type C virus, and putative human type C viruses [HL23V isolated from blood cells of a patient with acute myelogenous leukemia (HL23) and HEL-12V from human embryonic diploid cells (CIH-32)]. Two sera also reacted with C57BL/6 mouse leukemia induced by Friend virus. These results were obtained by indirect immunoelectron microscopy with various virus-producing cells and by absorption tests using as targets gibbon lymphosarcoma cells that release gibbon ape leukemia virus. In a previous report, the presence of natural antibody in sera from healthy gibbon apes was demonstrated. When the specificities of the human and gibbon natural antibodies were compared, the human natural antibody reacted with two nonproducing culture cell lines of human lymphocytic leukemia (CEM-A and MOLT) and with human embryonic diploid (CIH-1(V-) cells [which became type C virus-producing CIH-32(V+) cells after many passages], but did not react with normal gibbon spleen monolayer cells. In contrast, gibbon natural antibody showed no reaction with CEM-A, MOLT, and CIH-1(V-) cells but reacted with gibbon spleen monolayer cells. Neither human nor gibbon natural antibody that was reactive with gibbon ape leukemia virus crossreacted with feline leukemia virus and mouse wild-type AKR leukemia virus. The gibbon lymphosarcoma cells releasing gibbon ape leukemia virus were used in a screening study of sera from healthy humans. Out of 72 sera screened by indirect immunoelectron microscopy using this system, 55 were positive (76%), i.e., 26 out of 35 males (74%) and 29 out of 37 females (78%). The highest incidence of antibody production was in 1- to 10-year-olds and 31- to 40-year-olds, with the adults exhibiting higher levels. Differences in incidence of natural antibody were not found to be sex-linked. These findings suggest that type C RNA viruses related to the gibbon ape leukemia virus and simian (woolly monkey) sarcoma virus family as well as the baboon endogenous type C virus family may be widespread in humans."} {"id": "PMID:181766", "title": "In vivo fate of a behaviorally active ACTH 4-9 analog in rats after systemic administration.", "content": "In vivo fate of a threefold substituted ACTH 4-9 analog with a markedly potentiated behavioral activity, 4-Met(O2), 8-D-Lys, 9-Phe-ACTH 4-9, was investigated. The radioactive labeled [7-3H-Phe] ACTH 4-9 analog was administered IV, SC and orally in a dose of approximately 40 mug. Plasma concentrations of total radioactivity and intact peptide were determined at various periods after administration in urethane anesthetized rats. Oral administration was also performed with conscious animals. Maximal plasma concentrations were found 8 min after SC injection. After oral administration in anesthetized rats maximal plasma levels were reached 8 hr after administration; in conscious animals this took 4 hr. The initial volume of distribution was 5.9% of body weight and the initial half-life (t1/2) for intact peptide 4 min. Shortly after IV and SC administration relatively high and stable plasma levels of intact peptide were obtained, reflecting metabolic stability. This stability was also apparent from the metabolite patterns, which were determined in trichloroacetic acid extracts of plasma and brain by paperchromatography and paperelectrophoresis. The plasma profiles indicated increased stability of the labile 8Lys-9Phe bond by the introduction of an 8D-Lys residue in the peptide analog. Enzymatic attack of the analog took place predominantly at 6His-7Phe and 7Phe-8D-Lys. Formation of tritiated water occcurred in brain and the gastro-intestinal tract and was considerable; proteolysis in these compartments was higher than in plasma. High uptake of radioactivity was found in the kidney, but urinary excretion was low during the first 30 min. Uptake in brain was low and paralleled uptake in cerebrospinal fluid. Intact peptide concentrations/g fresh tissue were in the order of 10(-5)-10(-4) times the administered dose for all three routes.", "contents": "In vivo fate of a behaviorally active ACTH 4-9 analog in rats after systemic administration. In vivo fate of a threefold substituted ACTH 4-9 analog with a markedly potentiated behavioral activity, 4-Met(O2), 8-D-Lys, 9-Phe-ACTH 4-9, was investigated. The radioactive labeled [7-3H-Phe] ACTH 4-9 analog was administered IV, SC and orally in a dose of approximately 40 mug. Plasma concentrations of total radioactivity and intact peptide were determined at various periods after administration in urethane anesthetized rats. Oral administration was also performed with conscious animals. Maximal plasma concentrations were found 8 min after SC injection. After oral administration in anesthetized rats maximal plasma levels were reached 8 hr after administration; in conscious animals this took 4 hr. The initial volume of distribution was 5.9% of body weight and the initial half-life (t1/2) for intact peptide 4 min. Shortly after IV and SC administration relatively high and stable plasma levels of intact peptide were obtained, reflecting metabolic stability. This stability was also apparent from the metabolite patterns, which were determined in trichloroacetic acid extracts of plasma and brain by paperchromatography and paperelectrophoresis. The plasma profiles indicated increased stability of the labile 8Lys-9Phe bond by the introduction of an 8D-Lys residue in the peptide analog. Enzymatic attack of the analog took place predominantly at 6His-7Phe and 7Phe-8D-Lys. Formation of tritiated water occcurred in brain and the gastro-intestinal tract and was considerable; proteolysis in these compartments was higher than in plasma. High uptake of radioactivity was found in the kidney, but urinary excretion was low during the first 30 min. Uptake in brain was low and paralleled uptake in cerebrospinal fluid. Intact peptide concentrations/g fresh tissue were in the order of 10(-5)-10(-4) times the administered dose for all three routes."} {"id": "PMID:181770", "title": "The radiology of lung cancer.", "content": "Double reading of radiographs increases the likelihood of detecting pulmonary disease and, accordingly, physicians have an obligation to view the radiographic examinations performed on their patients, either with the radiologist or independently. It is also essential that the radiologist be proved with the clinical findings before he interprets the radiographs, a practice which will result in significant improvement in the accuracy of radiologic reports.", "contents": "The radiology of lung cancer. Double reading of radiographs increases the likelihood of detecting pulmonary disease and, accordingly, physicians have an obligation to view the radiographic examinations performed on their patients, either with the radiologist or independently. It is also essential that the radiologist be proved with the clinical findings before he interprets the radiographs, a practice which will result in significant improvement in the accuracy of radiologic reports."} {"id": "PMID:181771", "title": "[Mechanism of action and kinetics of lithium. I. Biochemical and experimental pharmacological findings after administration of lithium-conclusions on the mechanism of the therapeutic effect of lithium].", "content": "A comprehensive consideration of biochemical and pharmacodynamic lithium (Li) effects enabled an explanation of the Li mechanism (Fig 1). According to this concept, Li might possibly affect the activity of membrane-bound ATPases in dependence on the initial situation, dose and duration of application. Research into Li-kinetics suggested the participation of active process in the transport of the ion through the organism. Li-kinetics describes distribution within a multiple-compartment system and, with the exception of the resorption phase, its independent of the anion used. The elimination (half-life time 22 to 25 hrs) is limited by backward flow form the tissue.", "contents": "[Mechanism of action and kinetics of lithium. I. Biochemical and experimental pharmacological findings after administration of lithium-conclusions on the mechanism of the therapeutic effect of lithium]. A comprehensive consideration of biochemical and pharmacodynamic lithium (Li) effects enabled an explanation of the Li mechanism (Fig 1). According to this concept, Li might possibly affect the activity of membrane-bound ATPases in dependence on the initial situation, dose and duration of application. Research into Li-kinetics suggested the participation of active process in the transport of the ion through the organism. Li-kinetics describes distribution within a multiple-compartment system and, with the exception of the resorption phase, its independent of the anion used. The elimination (half-life time 22 to 25 hrs) is limited by backward flow form the tissue."} {"id": "PMID:181772", "title": "[Plasma ACTH, STH and other hormone levels in various groups under chlormethiazole, haloperidol or reserpine load in alchohol delirium, alcoholic hallucinations, and chronic alcoholism].", "content": "Studies of 135 men with safely diagnosed alcohol delirium mostly revealed increased ACTH blood values when sober and increased T4 values in about 1/3 of these patients. There is a correlation between the psychiatric clinical picture of the alcohol delirium and the ACTH content of the plasma. Under load with chloromethiazole, halperidole or with reserpine, there is a significant drop in the increased ACTH and T4 values. In an acute alcoholic hallucinosis (n=16) similar endocrinological changes as in most cases of safely diagnosed alcohol delirium were observed. In a chronic alcoholic hallucinosis (n=11) and in chronic alcoholics (n=31) the endocrinological values were similar to those of patients after alcohol delirium.", "contents": "[Plasma ACTH, STH and other hormone levels in various groups under chlormethiazole, haloperidol or reserpine load in alchohol delirium, alcoholic hallucinations, and chronic alcoholism]. Studies of 135 men with safely diagnosed alcohol delirium mostly revealed increased ACTH blood values when sober and increased T4 values in about 1/3 of these patients. There is a correlation between the psychiatric clinical picture of the alcohol delirium and the ACTH content of the plasma. Under load with chloromethiazole, halperidole or with reserpine, there is a significant drop in the increased ACTH and T4 values. In an acute alcoholic hallucinosis (n=16) similar endocrinological changes as in most cases of safely diagnosed alcohol delirium were observed. In a chronic alcoholic hallucinosis (n=11) and in chronic alcoholics (n=31) the endocrinological values were similar to those of patients after alcohol delirium."} {"id": "PMID:181773", "title": "[Biochemistry of depression].", "content": "1. In patients with endogenous depression a functional deficiency of noradrenalin and serotonin is presupposed. This hypothesis is based on examinations of the metabolites of these transmitter substances in the cerebrospinal fluid and in the urine. 2. Attempts to compensate the deficiency by means of precursors of the transmitter show a great variety of therapeutic effects. Possible metabolic regulations are discussed. 3. Changes of hormone metabolism are involved in the disease, these are discussed. 4. At present valid statements on the causes of a biochemical defect in depressive illness are not possible.", "contents": "[Biochemistry of depression]. 1. In patients with endogenous depression a functional deficiency of noradrenalin and serotonin is presupposed. This hypothesis is based on examinations of the metabolites of these transmitter substances in the cerebrospinal fluid and in the urine. 2. Attempts to compensate the deficiency by means of precursors of the transmitter show a great variety of therapeutic effects. Possible metabolic regulations are discussed. 3. Changes of hormone metabolism are involved in the disease, these are discussed. 4. At present valid statements on the causes of a biochemical defect in depressive illness are not possible."} {"id": "PMID:181768", "title": "Comparative study of the gamma-radiation-induced changes in the tissular levels of acyclic and cyclic adenosine phosphates.", "content": "Periodical measurement of total adenosine phosphates and cAMP in liver, intestinal mucosa and brain carried out in rats after irradiation with either 500 rads or 750 rads generally revealed high intratissular levels of these compounds, suggesting both a stimulated cellular synthesis and an abnormal redistribution in different tissues. The most interesting findings were those regarding the brain considering their close relationships with the clinical evolution of the animals and other previously described biochemical observations.", "contents": "Comparative study of the gamma-radiation-induced changes in the tissular levels of acyclic and cyclic adenosine phosphates. Periodical measurement of total adenosine phosphates and cAMP in liver, intestinal mucosa and brain carried out in rats after irradiation with either 500 rads or 750 rads generally revealed high intratissular levels of these compounds, suggesting both a stimulated cellular synthesis and an abnormal redistribution in different tissues. The most interesting findings were those regarding the brain considering their close relationships with the clinical evolution of the animals and other previously described biochemical observations."} {"id": "PMID:181775", "title": "Antinociceptive action of quipazine: relation to central serotonergic receptor stimulation.", "content": "Quipazine, a serotonin receptor stimulant, inhibited the response of rats to painful stimuli in two methods currently used to measure antinociception in these animals: the hot plate and tail compression test. The antinocicptive action was observed with doses ranging from 5 to 20 mg/kg i.p according to the test situation. The effect was significantly antagonized by a pretreatment with methergoline, a potent serotonin antagonist. An electrolytic lesion placed in the nucleus raphe medianus, which produced a marked decrease of serotonin in the forebrain did not, or only slightly, affected the effect of quipazine, depending on the method used to measure antinociception. It is suggested that quipazine can produce antinociceptive action in rats by interacting with a serotonergic mechanism. The action appears to be due mainly to a direct action on postsynaptic serotonin receptors, although a presynaptic component can also contribute to the effect of quipazine.", "contents": "Antinociceptive action of quipazine: relation to central serotonergic receptor stimulation. Quipazine, a serotonin receptor stimulant, inhibited the response of rats to painful stimuli in two methods currently used to measure antinociception in these animals: the hot plate and tail compression test. The antinocicptive action was observed with doses ranging from 5 to 20 mg/kg i.p according to the test situation. The effect was significantly antagonized by a pretreatment with methergoline, a potent serotonin antagonist. An electrolytic lesion placed in the nucleus raphe medianus, which produced a marked decrease of serotonin in the forebrain did not, or only slightly, affected the effect of quipazine, depending on the method used to measure antinociception. It is suggested that quipazine can produce antinociceptive action in rats by interacting with a serotonergic mechanism. The action appears to be due mainly to a direct action on postsynaptic serotonin receptors, although a presynaptic component can also contribute to the effect of quipazine."} {"id": "PMID:181780", "title": "An unusual upper abdominal gas pattern.", "content": "The case history of one patient is discussed to illustrate radiographic features, etiology and prognosis of gas bubbles in the gastric wall.", "contents": "An unusual upper abdominal gas pattern. The case history of one patient is discussed to illustrate radiographic features, etiology and prognosis of gas bubbles in the gastric wall."} {"id": "PMID:181781", "title": "Evaluation of ultrasonic and scintigraphic studies of the liver.", "content": "Ultrasonic and scintigraphic examination of the liver took place in 148 patients. 29 had normal livers, 36 had cirrhosis, 11 had obstructive jaundice, 12 had fatty livers, 60 had focal liver defects. In case of diffuse liver disease the accuracy of both methods is about the same except for fatty liver which is poorly diagnosed by scintigraphy. Focal liver disease is determined with a relative high percentage false-negative for scintigraphy and a relative high percentage false-positive for echography. It is recognized that previous knowledge of the scintigraphic result may raise the accuracy of ultrasound examination of the liver. As echography could distinguish cystic from solid lesions both methods of liver imaging are considered complementary.", "contents": "Evaluation of ultrasonic and scintigraphic studies of the liver. Ultrasonic and scintigraphic examination of the liver took place in 148 patients. 29 had normal livers, 36 had cirrhosis, 11 had obstructive jaundice, 12 had fatty livers, 60 had focal liver defects. In case of diffuse liver disease the accuracy of both methods is about the same except for fatty liver which is poorly diagnosed by scintigraphy. Focal liver disease is determined with a relative high percentage false-negative for scintigraphy and a relative high percentage false-positive for echography. It is recognized that previous knowledge of the scintigraphic result may raise the accuracy of ultrasound examination of the liver. As echography could distinguish cystic from solid lesions both methods of liver imaging are considered complementary."} {"id": "PMID:181782", "title": "Kinetics and imaging characteristics of 99mTC-labled complexes used for bone imaging.", "content": "Activity levels of 99TC-labeled compounds, 18F, and 85Sr were obtained at 1, 3, and 5 hr. postinjection in normal and healing fractured bone and in soft-tissue rat specimens. Serial diagnostic bone images and blood and urine kinetics were obtained in patients with each of the TC-labeled compounds. Computer-processed images were used to evaluate in vivo kinetics. 99mTC pyrophosphate provides the best overall characteristics for bone imaging. Improved quality and bioassay procedures are required, however, before any one agent can be designated the radiopharmaceutical of choice for diagnostic bone imaging.", "contents": "Kinetics and imaging characteristics of 99mTC-labled complexes used for bone imaging. Activity levels of 99TC-labeled compounds, 18F, and 85Sr were obtained at 1, 3, and 5 hr. postinjection in normal and healing fractured bone and in soft-tissue rat specimens. Serial diagnostic bone images and blood and urine kinetics were obtained in patients with each of the TC-labeled compounds. Computer-processed images were used to evaluate in vivo kinetics. 99mTC pyrophosphate provides the best overall characteristics for bone imaging. Improved quality and bioassay procedures are required, however, before any one agent can be designated the radiopharmaceutical of choice for diagnostic bone imaging."} {"id": "PMID:181783", "title": "Imaging of tumors involving bone with 13N-glutamic acid.", "content": "Nitrogen-13 labeled L-glutamic acid was evaluated as an imaging agent for tumors involving bone. The enzymatically prepared labeled compound was administered intravenously to dogs with spontaneous tumors, and tumor uptake was determined with a gamma camera and rectilinear scanner. These tumors were well visualized with 13N-glutamic acid, and the results compared favorably with uptake studies performed on the same animals with 99mTc-diphosphonate.", "contents": "Imaging of tumors involving bone with 13N-glutamic acid. Nitrogen-13 labeled L-glutamic acid was evaluated as an imaging agent for tumors involving bone. The enzymatically prepared labeled compound was administered intravenously to dogs with spontaneous tumors, and tumor uptake was determined with a gamma camera and rectilinear scanner. These tumors were well visualized with 13N-glutamic acid, and the results compared favorably with uptake studies performed on the same animals with 99mTc-diphosphonate."} {"id": "PMID:181784", "title": "Effect of pentagastrin, histalog, glucagon, secretin, and perchlorate on the gastric handling of 99mTc pertechnetate in mice.", "content": "Pentagastrin, histalog, glucagon, secretin, and perchlorate were intravenously injected into mice in order to investigate the hormonal regulation of 99mTc pertechnetate uptake by gastric mucosa. Pentagastrin significantly increased uptake; the effect of histalog was weaker. Secretin did not alter the uptake. Glucagon produced some diminution, and perchlorate significantly inhibited gastric uptake. Hormones may play a role in improving the sensitivity and specificity of diagnostic tests for Meckel's diverticulum.", "contents": "Effect of pentagastrin, histalog, glucagon, secretin, and perchlorate on the gastric handling of 99mTc pertechnetate in mice. Pentagastrin, histalog, glucagon, secretin, and perchlorate were intravenously injected into mice in order to investigate the hormonal regulation of 99mTc pertechnetate uptake by gastric mucosa. Pentagastrin significantly increased uptake; the effect of histalog was weaker. Secretin did not alter the uptake. Glucagon produced some diminution, and perchlorate significantly inhibited gastric uptake. Hormones may play a role in improving the sensitivity and specificity of diagnostic tests for Meckel's diverticulum."} {"id": "PMID:181785", "title": "Elective whole lung irradiation.", "content": "Whole lung irradiation has been effective in 10 of 17 patients irradiated solely electively (no demonstrable metastatic nodules) who are alive and well 2 to 5 years. Of an additional 17 patients with only one or two demonstrable pulmonary metastases (treated with resection or boost therapy plus whole lung irradiation), 6 are alive and well 5 to 8 years. Only one patient developed clinically significant postirradiation pneumonitis and this case proved to be fatal. Elective whole lung irradiation, especially in conjunction with modern adjuvant chemotherapy, shows promise in improving the survival of patients with tumors having a high propensity for metastasizing to the lungs.", "contents": "Elective whole lung irradiation. Whole lung irradiation has been effective in 10 of 17 patients irradiated solely electively (no demonstrable metastatic nodules) who are alive and well 2 to 5 years. Of an additional 17 patients with only one or two demonstrable pulmonary metastases (treated with resection or boost therapy plus whole lung irradiation), 6 are alive and well 5 to 8 years. Only one patient developed clinically significant postirradiation pneumonitis and this case proved to be fatal. Elective whole lung irradiation, especially in conjunction with modern adjuvant chemotherapy, shows promise in improving the survival of patients with tumors having a high propensity for metastasizing to the lungs."} {"id": "PMID:181790", "title": "Metabolism and effect of prostaglandin H2 in adipose tissue.", "content": "Prostaglandin H2 (PGH2) inhibited noradrenaline induced cyclic AMP accumulation in isolated rat fat cells in a dose-dependent manner. IC50 was 10-25 ng/ml both in the absence and in the presence of theophylline. The degree of inhibition produced by PGH2 increased with time of incubation. A stable PGH2 analog did not inhibit cyclic AMP accumulation. PGH2 was rapidly converted by isolated fat cells to PGD2, PGE2 and PGF2alpha' but no formation of thromboxane B2 was found either in vitro or in vivo. PGE2 was a more potent inhibitor than PGH2 of noradrenaline induced cyclic AMP accumulation. PGD2 enhanced cyclic AMP accumulation in a limited concentration interval, while PGF2alpha was essentially uneffective. Our results suggest that PGH2 is an inhibitor of cyclic AMP formation in isolated rat fat cells only after conversion to PGE2. A physiological role for PGH2 as a modulator of lipolysis is considered unlikely.", "contents": "Metabolism and effect of prostaglandin H2 in adipose tissue. Prostaglandin H2 (PGH2) inhibited noradrenaline induced cyclic AMP accumulation in isolated rat fat cells in a dose-dependent manner. IC50 was 10-25 ng/ml both in the absence and in the presence of theophylline. The degree of inhibition produced by PGH2 increased with time of incubation. A stable PGH2 analog did not inhibit cyclic AMP accumulation. PGH2 was rapidly converted by isolated fat cells to PGD2, PGE2 and PGF2alpha' but no formation of thromboxane B2 was found either in vitro or in vivo. PGE2 was a more potent inhibitor than PGH2 of noradrenaline induced cyclic AMP accumulation. PGD2 enhanced cyclic AMP accumulation in a limited concentration interval, while PGF2alpha was essentially uneffective. Our results suggest that PGH2 is an inhibitor of cyclic AMP formation in isolated rat fat cells only after conversion to PGE2. A physiological role for PGH2 as a modulator of lipolysis is considered unlikely."} {"id": "PMID:181792", "title": "Ultrastuctural study on the relations among nerve elements and ependymal cells of the \"Bradypus tridactylus\".", "content": "On hand of the electonmicroscope, the authors study 24 parts of the encephalic ventricles in samples of Bradypus tridactylus, relating the nervous structures to the ependymal lining, chiefly emphasizing the presence of intraventricular unmyelinated fibres. In various of these regions, typical nerve fibres and other intraventricular cell projections, that cannot be taken as nerve structures, because of the continuity they show along with ependymal cells, were observed. Finally they make an analysis of some functions related to arrangements of this nature.", "contents": "Ultrastuctural study on the relations among nerve elements and ependymal cells of the \"Bradypus tridactylus\". On hand of the electonmicroscope, the authors study 24 parts of the encephalic ventricles in samples of Bradypus tridactylus, relating the nervous structures to the ependymal lining, chiefly emphasizing the presence of intraventricular unmyelinated fibres. In various of these regions, typical nerve fibres and other intraventricular cell projections, that cannot be taken as nerve structures, because of the continuity they show along with ependymal cells, were observed. Finally they make an analysis of some functions related to arrangements of this nature."} {"id": "PMID:181804", "title": "In vitro cytochrome b5 binding to microsomal membranes: functional and non-functional levels.", "content": "A comparison of the apparent level of cytochrome binding b5 to liver and kidney microsomes was undertaken comparing values obtained by dithionite vs. NADH reduction. Significant differences both in the extent and specificity of binding to microsomes from liver and kidney were found. These results suggest careful consideration of the apparent binding site availability based on means of reduction is in order.", "contents": "In vitro cytochrome b5 binding to microsomal membranes: functional and non-functional levels. A comparison of the apparent level of cytochrome binding b5 to liver and kidney microsomes was undertaken comparing values obtained by dithionite vs. NADH reduction. Significant differences both in the extent and specificity of binding to microsomes from liver and kidney were found. These results suggest careful consideration of the apparent binding site availability based on means of reduction is in order."} {"id": "PMID:181805", "title": "Isolation of a cytopathic calf rotavirus.", "content": "The isolation and serial passage in secondary and continuous cultures of calf kidney cells of a cytopathic calf rotavirus is described.", "contents": "Isolation of a cytopathic calf rotavirus. The isolation and serial passage in secondary and continuous cultures of calf kidney cells of a cytopathic calf rotavirus is described."} {"id": "PMID:181806", "title": "Detection of immune complexes in the serum of dogs infected with canine adenovirus.", "content": "Evidence for the presence of circulating virus-immune complexes in dogs experimentally infected with canine adenovirus was found when deposits of canine IgG were present in the glomeruli of recipient mice. This passive transfer of complexes occurred only with serum taken at the height of the disease when antibody titres were low and when deposition of complexes in the donor dogs was maximal. Transfer of complexes was not obtained early in the disease (no circulating antibody and minimal deposition of complexes) nor later in the disease (high circulating antibody and minimal complex deposition).", "contents": "Detection of immune complexes in the serum of dogs infected with canine adenovirus. Evidence for the presence of circulating virus-immune complexes in dogs experimentally infected with canine adenovirus was found when deposits of canine IgG were present in the glomeruli of recipient mice. This passive transfer of complexes occurred only with serum taken at the height of the disease when antibody titres were low and when deposition of complexes in the donor dogs was maximal. Transfer of complexes was not obtained early in the disease (no circulating antibody and minimal deposition of complexes) nor later in the disease (high circulating antibody and minimal complex deposition)."} {"id": "PMID:181808", "title": "[Chemodectomas of the vagus nerve. Pathogenic hypothesis based on a review of 100 cases].", "content": "In connection with a personal case, 100 chemodectomas of the vagus described in the literature have been collected: revealing themselves in 75p. 100 of the cases in the form of cervical and pharyngeal tumours, 50p. 100 of the tumours of the vagal glomus involve some neurological manifestations mainly in the form of lesion of the lower cranial nerves. These appear to be either affected in isolation (41 p. 100) or in a dissociated manner (59 p. 100). Intra-cranial extension is rare (7 p. 100 of the cases) and delayed. Carotid angiography is characteristic. 76 p 100 are intra-vagal, 24 p. 100 are para-vagal and 60 p. 100 are located in the plexiform ganglion. Multifocal forms which account for 17 p. 100 of the cases are more usually, but not exclusively, familial. Surgical treatment is followed by sequelae or complications in more than half the cases. Close attention has been paid to pathogenetic theories: chemodectomas of the vagus may develop from type I chemoreceptor cells of the carotid glomera or from distinct cells with different properties (S.I.F. cells). They may equally well develop from nonchromaffin paraganglionic cells which have not migrated in the normal manner. The finding of such cells in the nerves of new-born babies and adults supports this theory, at least for some chemodectomas of the vagus.", "contents": "[Chemodectomas of the vagus nerve. Pathogenic hypothesis based on a review of 100 cases]. In connection with a personal case, 100 chemodectomas of the vagus described in the literature have been collected: revealing themselves in 75p. 100 of the cases in the form of cervical and pharyngeal tumours, 50p. 100 of the tumours of the vagal glomus involve some neurological manifestations mainly in the form of lesion of the lower cranial nerves. These appear to be either affected in isolation (41 p. 100) or in a dissociated manner (59 p. 100). Intra-cranial extension is rare (7 p. 100 of the cases) and delayed. Carotid angiography is characteristic. 76 p 100 are intra-vagal, 24 p. 100 are para-vagal and 60 p. 100 are located in the plexiform ganglion. Multifocal forms which account for 17 p. 100 of the cases are more usually, but not exclusively, familial. Surgical treatment is followed by sequelae or complications in more than half the cases. Close attention has been paid to pathogenetic theories: chemodectomas of the vagus may develop from type I chemoreceptor cells of the carotid glomera or from distinct cells with different properties (S.I.F. cells). They may equally well develop from nonchromaffin paraganglionic cells which have not migrated in the normal manner. The finding of such cells in the nerves of new-born babies and adults supports this theory, at least for some chemodectomas of the vagus."} {"id": "PMID:181809", "title": "[Ultrastructural aspects of peripheral nerve lesions in one case of Farber's disease].", "content": "The patient is a girl who had amyotrophia, dyspnea and juxta-articular nodes. She died at the age of 14 months. Ultrastructural examination of a sural nerve biopsy revealed anormal inclusions in the cytoplasm of numerous myelinated fibres. They are round or oval, and empty, sometimes with a great diameter. Some histiocytes show also such bodies. These are different from those seen in the other neurolipidosis.", "contents": "[Ultrastructural aspects of peripheral nerve lesions in one case of Farber's disease]. The patient is a girl who had amyotrophia, dyspnea and juxta-articular nodes. She died at the age of 14 months. Ultrastructural examination of a sural nerve biopsy revealed anormal inclusions in the cytoplasm of numerous myelinated fibres. They are round or oval, and empty, sometimes with a great diameter. Some histiocytes show also such bodies. These are different from those seen in the other neurolipidosis."} {"id": "PMID:181813", "title": "[The risk of tuberculosis in students of professional schools].", "content": "In four technical schools in a Burcharest district, the first grade scholars were tested at the beginning of the term with 2 units PPD; those with a reaction of 0--9 mm received BCG vaccine. After 6 months, in the 3rd term, they were controlled by MMR examination which was repeated in the second year. The incidence of tuberculosis detected by X-ray and clinically was of 298.8 per 100 000 in the frist year and 283.6 per 100000 in the second year. In all disease cases but one the intradermoreation and greater than or equal to 15 mm which may thus be considered the risk group (a risk of 9.5 per thousand); there were no cases among the children revaccinated with BCG. In conclusion it is recommended to apply in adolescent communities tuberculin testing and BCG revaccination of the non-infected children 0--9 mm) in their first term and periodical X-ray control of the risk group, i.e. those with a reaction of 15 mm or more.", "contents": "[The risk of tuberculosis in students of professional schools]. In four technical schools in a Burcharest district, the first grade scholars were tested at the beginning of the term with 2 units PPD; those with a reaction of 0--9 mm received BCG vaccine. After 6 months, in the 3rd term, they were controlled by MMR examination which was repeated in the second year. The incidence of tuberculosis detected by X-ray and clinically was of 298.8 per 100 000 in the frist year and 283.6 per 100000 in the second year. In all disease cases but one the intradermoreation and greater than or equal to 15 mm which may thus be considered the risk group (a risk of 9.5 per thousand); there were no cases among the children revaccinated with BCG. In conclusion it is recommended to apply in adolescent communities tuberculin testing and BCG revaccination of the non-infected children 0--9 mm) in their first term and periodical X-ray control of the risk group, i.e. those with a reaction of 15 mm or more."} {"id": "PMID:181815", "title": "[Problems concerning the etiopathogenesis of bronchopulmonary suppurations].", "content": "The data supplied by analysis of more than 1 000 patients pointed to the wide range of the causal factors, the role of focal infections of the upper respiratory and digestive tracts and the mechanisms that interfere in the determinism of the bronchopulmonary suppurative syndrome, the septic particles migrating as a rule along the bronchogenic route.", "contents": "[Problems concerning the etiopathogenesis of bronchopulmonary suppurations]. The data supplied by analysis of more than 1 000 patients pointed to the wide range of the causal factors, the role of focal infections of the upper respiratory and digestive tracts and the mechanisms that interfere in the determinism of the bronchopulmonary suppurative syndrome, the septic particles migrating as a rule along the bronchogenic route."} {"id": "PMID:181816", "title": "[Current incidence of the aged among hospitalized tuberculosis patients].", "content": "A survey including 10 442 tuberculosis patients hospitalized in a sanatorium showed that 1 086 (10.42%) were 65 years old or older, the proportion increasing from 5.21% in 1964 to 12.78% in 1973 (p less than 0.001). The patients over 70 represented 3.73% of the total, increasing twofold in the course of ten years, from 2.37% to 4.15% (p less than 0.05). There was a rural prevalence, i.e. 11.9% as against 6.85% from urban areas (p less than 0.001), and in the over 70 years age group 4.13% as against 2.74% (p less than 0.001).", "contents": "[Current incidence of the aged among hospitalized tuberculosis patients]. A survey including 10 442 tuberculosis patients hospitalized in a sanatorium showed that 1 086 (10.42%) were 65 years old or older, the proportion increasing from 5.21% in 1964 to 12.78% in 1973 (p less than 0.001). The patients over 70 represented 3.73% of the total, increasing twofold in the course of ten years, from 2.37% to 4.15% (p less than 0.05). There was a rural prevalence, i.e. 11.9% as against 6.85% from urban areas (p less than 0.001), and in the over 70 years age group 4.13% as against 2.74% (p less than 0.001)."} {"id": "PMID:181817", "title": "[Respiratory consequences of thoracopulmonary surgical operations in children and adolescents].", "content": "Spirographic investigations were carried out in a lot of 125 children and adolescents with surgical exeresis or collapse, performed between 1965 and 1972 for suppurations, tuberculosis and other thoraco-pulmonary diseases. Spirographic determinations before and 1--2 months after surgery showed that the postoperative sequelae were milder in children than in adults. Recovery of the ventilation function was more complete than that of the pulmonary circulation. The necessity of a correct postoperative care and systematic, prolonged respiratory kinesitherapy is emphasized.", "contents": "[Respiratory consequences of thoracopulmonary surgical operations in children and adolescents]. Spirographic investigations were carried out in a lot of 125 children and adolescents with surgical exeresis or collapse, performed between 1965 and 1972 for suppurations, tuberculosis and other thoraco-pulmonary diseases. Spirographic determinations before and 1--2 months after surgery showed that the postoperative sequelae were milder in children than in adults. Recovery of the ventilation function was more complete than that of the pulmonary circulation. The necessity of a correct postoperative care and systematic, prolonged respiratory kinesitherapy is emphasized."} {"id": "PMID:181814", "title": "[Experience in the field of microbial allergic asthma].", "content": "The present paper reports on the effect of prolonged microbial hyposensitization applied in 206 cases of microbial allergic asthma in comparison to 95 asthmatic patients of the same category in which this treatment was not applied; improvement was obtained in 78% of the former lot as against 17% in the latter. The quanlity of the improvement obtained and the dependence of the results upon the various diagnostic criteria used are discussed. Microbial hyposensitization has proved efficient in asthmatic patients although its mechanism of action is not yet known, nor the difference that exists from this point of view with the current microbial vaccination. The data obtained suggest that microbial hyposensitization acts by the mechanism of microbial vaccination in all the variants of infectious asthma.", "contents": "[Experience in the field of microbial allergic asthma]. The present paper reports on the effect of prolonged microbial hyposensitization applied in 206 cases of microbial allergic asthma in comparison to 95 asthmatic patients of the same category in which this treatment was not applied; improvement was obtained in 78% of the former lot as against 17% in the latter. The quanlity of the improvement obtained and the dependence of the results upon the various diagnostic criteria used are discussed. Microbial hyposensitization has proved efficient in asthmatic patients although its mechanism of action is not yet known, nor the difference that exists from this point of view with the current microbial vaccination. The data obtained suggest that microbial hyposensitization acts by the mechanism of microbial vaccination in all the variants of infectious asthma."} {"id": "PMID:181818", "title": "[Inter-relations between pulmonary tuberculosis and diabetes mellitus].", "content": "The glucose tolerance test was applied in 50 patients with cavitary pulmonary tuberculosis. In 8 cases chemical diabetes was found representing a proportion of 16% as compared to 2.13% in the rest of the population. Certain possible etiopathogenic factors are discussed: sex, age, environment, nutritional status, age of the disease and tuberculostatic medication. Tuberculosis may be considered as a \"diabetogenic risk\" factor.", "contents": "[Inter-relations between pulmonary tuberculosis and diabetes mellitus]. The glucose tolerance test was applied in 50 patients with cavitary pulmonary tuberculosis. In 8 cases chemical diabetes was found representing a proportion of 16% as compared to 2.13% in the rest of the population. Certain possible etiopathogenic factors are discussed: sex, age, environment, nutritional status, age of the disease and tuberculostatic medication. Tuberculosis may be considered as a \"diabetogenic risk\" factor."} {"id": "PMID:181834", "title": "Effect of cortisone and acth on the phospholipids of human amniotic fluid and lung tissue in early gestation.", "content": "Fifteen physically healthy women who received permission for legal abortion on sociomedical grounds in the second trimester of pregnancy were given either cortisone acetate per os or adrenocorticotrophic hormone (ACTH) intramuscularyly for 3 days previous to hysterotomy. Eight other patients served as controls. The phospholipid composition of amniotic fluid, fetal lung washings, and lung tissue was analyzed. In the cortisone group there was a significant increase in the proportion of palmitic acid in the lung tissue lecithins linked to a corresponding decrease in the oleic acid. A similar tendency was observed in the ACTH group, but the changes were not significant. The investigation suggests that the human fetal lung already at this early stage of development is capable of responding to the action of cortisone by a relative increase in the synthesis of dipalmitoyllecithin.", "contents": "Effect of cortisone and acth on the phospholipids of human amniotic fluid and lung tissue in early gestation. Fifteen physically healthy women who received permission for legal abortion on sociomedical grounds in the second trimester of pregnancy were given either cortisone acetate per os or adrenocorticotrophic hormone (ACTH) intramuscularyly for 3 days previous to hysterotomy. Eight other patients served as controls. The phospholipid composition of amniotic fluid, fetal lung washings, and lung tissue was analyzed. In the cortisone group there was a significant increase in the proportion of palmitic acid in the lung tissue lecithins linked to a corresponding decrease in the oleic acid. A similar tendency was observed in the ACTH group, but the changes were not significant. The investigation suggests that the human fetal lung already at this early stage of development is capable of responding to the action of cortisone by a relative increase in the synthesis of dipalmitoyllecithin."} {"id": "PMID:181835", "title": "Cord blood cholesterol, triglyceride, and lipoprotein pattern from two districts in Norway.", "content": "Lipid levels of cord blood from two districts in Norway were studied. Although the mean levels of cholesterol and triglycerides in the two populations were similar, high cord blood lipid levels were more frequently found in a population in Finnmark in northern Norway than in Bergen in western Norway. In Bergen the 95-percentile value for both cholesterol and triglycerides was 90 mg/100 ml. In Finnmark the corresponding values were 100 and 115 mg/100 ml. The lipid levels in cord blood from children of Norwegian, Finnish, and Lappish origin were nearly identical. The frequency of lipoprotein subfractions as distinct bands between beta and pre-beta fractions in polyacrylamide gel electrophoresis was the same in the two populations. Thus no genetic difference was found in lipoprotein patterns of cord blood in the populations of western and northern Norway.", "contents": "Cord blood cholesterol, triglyceride, and lipoprotein pattern from two districts in Norway. Lipid levels of cord blood from two districts in Norway were studied. Although the mean levels of cholesterol and triglycerides in the two populations were similar, high cord blood lipid levels were more frequently found in a population in Finnmark in northern Norway than in Bergen in western Norway. In Bergen the 95-percentile value for both cholesterol and triglycerides was 90 mg/100 ml. In Finnmark the corresponding values were 100 and 115 mg/100 ml. The lipid levels in cord blood from children of Norwegian, Finnish, and Lappish origin were nearly identical. The frequency of lipoprotein subfractions as distinct bands between beta and pre-beta fractions in polyacrylamide gel electrophoresis was the same in the two populations. Thus no genetic difference was found in lipoprotein patterns of cord blood in the populations of western and northern Norway."} {"id": "PMID:181836", "title": "Precipitation of plasma lipoproteins by PEG-6000 and its evaluation with electrophoresis and ultracentrifugation.", "content": "A neutral polymer precipitation procedure for fractionation of human plasma lipoproteins is described. The method was also tested preliminarily for fractionation of rat plasma lipoproteins. Polyethylene glycol-6000 (PEG-6000) at a concentration of about 12% and at pH 7.9 precipitated human plasma very low density (VLDL) and low-density (LDL) lipoproteins completely. Precipitation was independent of time and temperature. VLDL and LDL could not be precipitated separately. Polyethylene glycol-6000 precipitation can be used for rapid determination of high-density (HDL) lipids and of the ratio of HDL to LDL lipids.", "contents": "Precipitation of plasma lipoproteins by PEG-6000 and its evaluation with electrophoresis and ultracentrifugation. A neutral polymer precipitation procedure for fractionation of human plasma lipoproteins is described. The method was also tested preliminarily for fractionation of rat plasma lipoproteins. Polyethylene glycol-6000 (PEG-6000) at a concentration of about 12% and at pH 7.9 precipitated human plasma very low density (VLDL) and low-density (LDL) lipoproteins completely. Precipitation was independent of time and temperature. VLDL and LDL could not be precipitated separately. Polyethylene glycol-6000 precipitation can be used for rapid determination of high-density (HDL) lipids and of the ratio of HDL to LDL lipids."} {"id": "PMID:181837", "title": "Radioimmunoassay of triiodothyronine in human serum with special reference to methodological problems.", "content": "A radioimmunoassay for measuring the level of triiodothyronine in human serum has been developed and studied with respect to interference from hormone-binding substances present in human serum. Dextran-coated charcoal was used for the separation of free and antibody-bound hormone. ANS (8-anilino-1-naphthalenesulfonic acid) was used to reduce the interference from hormone-binding substances in serum. Extraction of the hormone by ethanol before the radioimmunoassay did not solve the problem of interference, even in the presence of an internal standard. The protein concentration in the assay system strongly influenced the charcoal adsorption of free and antibody-bound hormone, and optimal concentrations for both proteins and ANS had to be worked out to get a reliable assay for unextracted serum.", "contents": "Radioimmunoassay of triiodothyronine in human serum with special reference to methodological problems. A radioimmunoassay for measuring the level of triiodothyronine in human serum has been developed and studied with respect to interference from hormone-binding substances present in human serum. Dextran-coated charcoal was used for the separation of free and antibody-bound hormone. ANS (8-anilino-1-naphthalenesulfonic acid) was used to reduce the interference from hormone-binding substances in serum. Extraction of the hormone by ethanol before the radioimmunoassay did not solve the problem of interference, even in the presence of an internal standard. The protein concentration in the assay system strongly influenced the charcoal adsorption of free and antibody-bound hormone, and optimal concentrations for both proteins and ANS had to be worked out to get a reliable assay for unextracted serum."} {"id": "PMID:181833", "title": "Importance of associated viral and bacterial infections in the production of acute pneumonias.", "content": "Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities.", "contents": "Importance of associated viral and bacterial infections in the production of acute pneumonias. Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities."} {"id": "PMID:181838", "title": "A protein-binding assay for direct determination of adenosine 3',5'-monophosphate in amniotic fluid, cerebrospinal fluid, plasma, and urine.", "content": "An adenosine 3',5'-monophosphate (cyclic AMP)-binding protein was isolated from bovine skeletal muscle. This preparation showed maximum binding capacity for cyclic AMP at the physiological pH of amniotic fluid, cerebrospinal fluid, and plasma and had a high association constant of 1.4x10(9) 1/mol. This preparation of binding protein, together with albumin and EDTA in the assay buffer, gave a sensitive and specific competitive protein-binding assay that permitted direct determination of cyclic AMP in the biological fluids mentioned above.", "contents": "A protein-binding assay for direct determination of adenosine 3',5'-monophosphate in amniotic fluid, cerebrospinal fluid, plasma, and urine. An adenosine 3',5'-monophosphate (cyclic AMP)-binding protein was isolated from bovine skeletal muscle. This preparation showed maximum binding capacity for cyclic AMP at the physiological pH of amniotic fluid, cerebrospinal fluid, and plasma and had a high association constant of 1.4x10(9) 1/mol. This preparation of binding protein, together with albumin and EDTA in the assay buffer, gave a sensitive and specific competitive protein-binding assay that permitted direct determination of cyclic AMP in the biological fluids mentioned above."} {"id": "PMID:181839", "title": "Effects of granulocyte neutral proteases on complement components.", "content": "The proteolytic effects of collagenase and elastase from human granulocytes were investigated on the human complement components C3 and C5 in serum and with purified components. The conversion of C3 was analyzed with crossed immunoelectrophoresis as described by Ganrot, and the conversion of C5 was detected with immunoelectrophoresis according to Scheidegger's method. Collagenase converted C3 to C3b but had no detectable effect on C5. Elastase converted C3 to C3b and converted C5 to a C5b-like fragment. The proteolysis by collagenase and elastase in serum was not detectable until the molar ratio for enzyme to the protease inhibitors alpha1-antitrypsin and alpha2-macroglobulin was greater than 1.", "contents": "Effects of granulocyte neutral proteases on complement components. The proteolytic effects of collagenase and elastase from human granulocytes were investigated on the human complement components C3 and C5 in serum and with purified components. The conversion of C3 was analyzed with crossed immunoelectrophoresis as described by Ganrot, and the conversion of C5 was detected with immunoelectrophoresis according to Scheidegger's method. Collagenase converted C3 to C3b but had no detectable effect on C5. Elastase converted C3 to C3b and converted C5 to a C5b-like fragment. The proteolysis by collagenase and elastase in serum was not detectable until the molar ratio for enzyme to the protease inhibitors alpha1-antitrypsin and alpha2-macroglobulin was greater than 1."} {"id": "PMID:181841", "title": "Sustained tolerance to a specific effect of ethanol on posttetanic potentiation in Aplysia.", "content": "Perfusion with 0.8 molar ethanol in a seawater specifically accelerates the rate of decay of posttetanic potentiation observed after repetitive electrical stimulation of an identified synapse in the abdominal ganglion of Aplysia californica. Repeated perfusion with seawater alternately with and without ethanol leads to a progressive diminution of this specific effect of ethanol, such that after the third application ethanol no longer has any effect on the rate constant of decay of posttetanic poteniation. This tolerance to the specific effects of ethanol persists for at least 11 hours after the last application of ethanol.", "contents": "Sustained tolerance to a specific effect of ethanol on posttetanic potentiation in Aplysia. Perfusion with 0.8 molar ethanol in a seawater specifically accelerates the rate of decay of posttetanic potentiation observed after repetitive electrical stimulation of an identified synapse in the abdominal ganglion of Aplysia californica. Repeated perfusion with seawater alternately with and without ethanol leads to a progressive diminution of this specific effect of ethanol, such that after the third application ethanol no longer has any effect on the rate constant of decay of posttetanic poteniation. This tolerance to the specific effects of ethanol persists for at least 11 hours after the last application of ethanol."} {"id": "PMID:181842", "title": "Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites.", "content": "The zona reticulata, the subdivision of the substantia nigra containing dendrites of the dopaminergic nigro-neostriatal neurons, contains dopamine-sensitive adenylate cyclase activity. This nigral dopamine receptor is similar to the striatal dopamine receptor. These and previous data suggest a physiological role (or roles) for dopamine in the substantia nigra.", "contents": "Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites. The zona reticulata, the subdivision of the substantia nigra containing dendrites of the dopaminergic nigro-neostriatal neurons, contains dopamine-sensitive adenylate cyclase activity. This nigral dopamine receptor is similar to the striatal dopamine receptor. These and previous data suggest a physiological role (or roles) for dopamine in the substantia nigra."} {"id": "PMID:181843", "title": "Ischemic areas in perfused rat hearts: measurement by NADH fluorescence photography.", "content": "Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of perfused rat hearts was photographed to provide a two-dimensional recording of NADH levels. Sodium Amytal inhibition of NADH oxidation resulted in a homogeneous increase in NADH fluorescence, while lowering perfusion pressure from 55 to 10 torr caused a heterogeneous increase in NADH fluorescence, reflecting the heterogeneous oxygen delivery at this low pressure. Local ischemia resulted in a well-defined region of high NADH fluorescence that corresponded to the region of ischemic inslut. The sharp transition between the ischemic and normoxic areas demonstrated that the hypoxic interface separating the two areas must be quite small.", "contents": "Ischemic areas in perfused rat hearts: measurement by NADH fluorescence photography. Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of perfused rat hearts was photographed to provide a two-dimensional recording of NADH levels. Sodium Amytal inhibition of NADH oxidation resulted in a homogeneous increase in NADH fluorescence, while lowering perfusion pressure from 55 to 10 torr caused a heterogeneous increase in NADH fluorescence, reflecting the heterogeneous oxygen delivery at this low pressure. Local ischemia resulted in a well-defined region of high NADH fluorescence that corresponded to the region of ischemic inslut. The sharp transition between the ischemic and normoxic areas demonstrated that the hypoxic interface separating the two areas must be quite small."} {"id": "PMID:181840", "title": "Herpesvirus infections in renal allograft recipients.", "content": "17 of 37 immunosuppressed renal allograft recipients developed clinical and/or serological evidence of herpes simplex virus infections, 7 of 83 developed a zoster rash, 85 of loo had evidence of cytomegalovirus infection and in 3 of 30 an active Epstein-Barr virus was seen.", "contents": "Herpesvirus infections in renal allograft recipients. 17 of 37 immunosuppressed renal allograft recipients developed clinical and/or serological evidence of herpes simplex virus infections, 7 of 83 developed a zoster rash, 85 of loo had evidence of cytomegalovirus infection and in 3 of 30 an active Epstein-Barr virus was seen."} {"id": "PMID:181845", "title": "Selective in vitro growth of T lymphocytes from normal human bone marrows.", "content": "Selective growth of T lymphocytes occurred when unfractionated normal human bone marrow cells were cultured with conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes (Ly-CM). Cultures of up to 90 percent T cells have been maintained for more than 9 months. The T cells exhibited a strict growth dependence upon Ly-CM and were consistently negative for Epstein-Barr viral information.", "contents": "Selective in vitro growth of T lymphocytes from normal human bone marrows. Selective growth of T lymphocytes occurred when unfractionated normal human bone marrow cells were cultured with conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes (Ly-CM). Cultures of up to 90 percent T cells have been maintained for more than 9 months. The T cells exhibited a strict growth dependence upon Ly-CM and were consistently negative for Epstein-Barr viral information."} {"id": "PMID:181846", "title": "[Ligation of lymphatic ducts in treatment of arteriosclerosis. 550 operated cases reported over a period of 9 years].", "content": "In all diseases where there is an important loss of lymph, e.g. chylothorax, chyloperitoneum, exsudative enteropathy chyloduodenal fistula, we observed not only a fall in the serum proteins and calcium, but also a fall in lipids and cholesterol. We first carried out ligature of the lymphatic ducts in numerous dogs. Since 1966, we have carried out this ligature in 550 arteriosclerotic patients, aged less than 52 years. The metabolic changes observed over a period of 9 years were very marked. Clinically, in 100 patients who underwent classical reconstructive arterial surgery, the association of ligature of the lymphatic ducts reduced by half, after a period of 6 years, the complications normally observed.", "contents": "[Ligation of lymphatic ducts in treatment of arteriosclerosis. 550 operated cases reported over a period of 9 years]. In all diseases where there is an important loss of lymph, e.g. chylothorax, chyloperitoneum, exsudative enteropathy chyloduodenal fistula, we observed not only a fall in the serum proteins and calcium, but also a fall in lipids and cholesterol. We first carried out ligature of the lymphatic ducts in numerous dogs. Since 1966, we have carried out this ligature in 550 arteriosclerotic patients, aged less than 52 years. The metabolic changes observed over a period of 9 years were very marked. Clinically, in 100 patients who underwent classical reconstructive arterial surgery, the association of ligature of the lymphatic ducts reduced by half, after a period of 6 years, the complications normally observed."} {"id": "PMID:181847", "title": "[Acute agranulocytosis induced by pyramidon or phenothiazines. Apropos of 31 cases].", "content": "The authors present 31 cases of acute agranulocytosis due to drugs. 27 resulted from amidopyrine poisoning and 4 were due to phenothiazines. The clinical picture in most cases, was that of severe septicemia with lesions of the mucosae. On blood count agranulocytosis was complete, associated on bone marrow examination with an appearance of selective hypoplasia of the granular series or an aspect of maturation blockage at the stage of the myelocyte or the metamyelocyte. The course was fatal in 6 cases. A search for leukocyte agglutinating antibodies, carried out in 29 cases, was positive in only 5 cases. These facts correspond, on the whole, to the, clinical and etiological data found in the literature. Although the agranulocytoses induced by phenothiazines, seem to be mainly of toxic origin, the agranulocytoses induced by amidopyrine associated both an immunological mechanism and a toxic mechanism. Among all the biological tests proposed, the most useful is the le ukocyte agglutination test, but the serological diagnosis is rarely conclusive.", "contents": "[Acute agranulocytosis induced by pyramidon or phenothiazines. Apropos of 31 cases]. The authors present 31 cases of acute agranulocytosis due to drugs. 27 resulted from amidopyrine poisoning and 4 were due to phenothiazines. The clinical picture in most cases, was that of severe septicemia with lesions of the mucosae. On blood count agranulocytosis was complete, associated on bone marrow examination with an appearance of selective hypoplasia of the granular series or an aspect of maturation blockage at the stage of the myelocyte or the metamyelocyte. The course was fatal in 6 cases. A search for leukocyte agglutinating antibodies, carried out in 29 cases, was positive in only 5 cases. These facts correspond, on the whole, to the, clinical and etiological data found in the literature. Although the agranulocytoses induced by phenothiazines, seem to be mainly of toxic origin, the agranulocytoses induced by amidopyrine associated both an immunological mechanism and a toxic mechanism. Among all the biological tests proposed, the most useful is the le ukocyte agglutination test, but the serological diagnosis is rarely conclusive."} {"id": "PMID:181848", "title": "[Study of circulation of cerebro-spinal fluid using indium 111 DTPA. Apropos of 300 cases].", "content": "A study of the C.S.F. circulation by intrathecal injection of radioactive tracers has become a common technic of neurological exploration. Among the molecules used at present, Indium111 DTPA has numerous advantages for this type of study. It is a chelating agent, the renal clearance of which is rapid and which has no toxicity at the dose injected. Indium111 is a product of the cyclotron and the physical period (2.8 days) is compatible with the duration of the examination. Finally the dose of radioactivity delivered by this isotope is less than that Iodine131, Technetium99m and Ytterbium169. In normal subjects after injection by the lumbar route, the average biological period measured by external counting lies between 20 and 28 hours. A study of the circulation of the C.S.F. is particularly useful in patients suspected of hydrocephalus. It permits finer diagnosis and shows the indications and type of by pass operation that may be neccssary. A marked increase in the biological period of Indium111-DTPA seems to be a good indication for such an operation. Our experience of 300 patients has shown the interest of the use of Indium111-DTPA which now seems to be the best radio-isotope for the study of the subarachnoid space.", "contents": "[Study of circulation of cerebro-spinal fluid using indium 111 DTPA. Apropos of 300 cases]. A study of the C.S.F. circulation by intrathecal injection of radioactive tracers has become a common technic of neurological exploration. Among the molecules used at present, Indium111 DTPA has numerous advantages for this type of study. It is a chelating agent, the renal clearance of which is rapid and which has no toxicity at the dose injected. Indium111 is a product of the cyclotron and the physical period (2.8 days) is compatible with the duration of the examination. Finally the dose of radioactivity delivered by this isotope is less than that Iodine131, Technetium99m and Ytterbium169. In normal subjects after injection by the lumbar route, the average biological period measured by external counting lies between 20 and 28 hours. A study of the circulation of the C.S.F. is particularly useful in patients suspected of hydrocephalus. It permits finer diagnosis and shows the indications and type of by pass operation that may be neccssary. A marked increase in the biological period of Indium111-DTPA seems to be a good indication for such an operation. Our experience of 300 patients has shown the interest of the use of Indium111-DTPA which now seems to be the best radio-isotope for the study of the subarachnoid space."} {"id": "PMID:181849", "title": "[Bacteroides infections].", "content": "The authors analyse 42 cases of bacteroides infection regrouping bacteremia and localised infection collected over a period of one year. The route of entry was almost always digestive. The prognosis seems mainly to depend on the background. The bacteriological diagnosis is now easy and germ-sensitivy is stereotyped.", "contents": "[Bacteroides infections]. The authors analyse 42 cases of bacteroides infection regrouping bacteremia and localised infection collected over a period of one year. The route of entry was almost always digestive. The prognosis seems mainly to depend on the background. The bacteriological diagnosis is now easy and germ-sensitivy is stereotyped."} {"id": "PMID:181850", "title": "[Cerebral gigantism. Review of the literature apropos of one case].", "content": "The authors report a case of cerebral gigantism and review 83 cases found in the world literature. The diagnosis depends on the association of several factors, none of which alone are specific but which, on the whole, form a fairly characteristic picture. Large size at birth, leading only rarely to gigantism at adult age. Facial dysmorphia of acromegaloid type. Ecephalopathy with mental deficiency without any neuroradiological abnormality. Finally, endocrine investigations and somatotropic function were normal. No etiology has been found up to now. The most satisfactory theory is that of a hypothalamopituitary disturbance. Treatment may simple avoid excess height at adult age and is based on sex hormone therapy to accelerate bony maturation.", "contents": "[Cerebral gigantism. Review of the literature apropos of one case]. The authors report a case of cerebral gigantism and review 83 cases found in the world literature. The diagnosis depends on the association of several factors, none of which alone are specific but which, on the whole, form a fairly characteristic picture. Large size at birth, leading only rarely to gigantism at adult age. Facial dysmorphia of acromegaloid type. Ecephalopathy with mental deficiency without any neuroradiological abnormality. Finally, endocrine investigations and somatotropic function were normal. No etiology has been found up to now. The most satisfactory theory is that of a hypothalamopituitary disturbance. Treatment may simple avoid excess height at adult age and is based on sex hormone therapy to accelerate bony maturation."} {"id": "PMID:181856", "title": "Angiographic evaluation of hepatoma for surgical treatment.", "content": "Celiac and superior mesenteric arteriography of 60 patients with primary carcinoma of the liver was evaluated retrospectively to select patients properly for hepatic lobectomy, ligation of the hepatic artery or temporary occlusion of the hepatic artery. The angiograms were studied from the viewpoints of origin of the hepatic artery, location of hepatomas, macroscopic type of hepatomas, tumor supplying arteries, patency of the portal vein and coexistence of cirrhosis of the liver. It is stressed that an exact knowledge of these items before operation is important in performing any type of surgical treatment for patients with hepatomas. Resectability of the tumor in the present series of patients was possible in 11 patients, and in the recently seen patients with nonresectable hepatomas, ligation or repeated temporary occlusion of the hepatic artery or both have been performed with postoperative infusion chemotherapy.", "contents": "Angiographic evaluation of hepatoma for surgical treatment. Celiac and superior mesenteric arteriography of 60 patients with primary carcinoma of the liver was evaluated retrospectively to select patients properly for hepatic lobectomy, ligation of the hepatic artery or temporary occlusion of the hepatic artery. The angiograms were studied from the viewpoints of origin of the hepatic artery, location of hepatomas, macroscopic type of hepatomas, tumor supplying arteries, patency of the portal vein and coexistence of cirrhosis of the liver. It is stressed that an exact knowledge of these items before operation is important in performing any type of surgical treatment for patients with hepatomas. Resectability of the tumor in the present series of patients was possible in 11 patients, and in the recently seen patients with nonresectable hepatomas, ligation or repeated temporary occlusion of the hepatic artery or both have been performed with postoperative infusion chemotherapy."} {"id": "PMID:181857", "title": "Lack of specificity for detection of breast lesions with radioactive cesium chloride.", "content": "Detection of breast disease at an early stage was evaluated with 131CsCl. The tissue distribution study showed that malignant tumors could be distinguished from both benign and normal tissue by the degree of 131Cs concentration. However, the external counting method was not sensitive enough to warrant general application to patients with a suspected malignant tumor of the breast. False-positive breast study findings using radionuclides, such as 131CsCl, require close follow-up study in view of possible malignant changes in benign disease of the breast.", "contents": "Lack of specificity for detection of breast lesions with radioactive cesium chloride. Detection of breast disease at an early stage was evaluated with 131CsCl. The tissue distribution study showed that malignant tumors could be distinguished from both benign and normal tissue by the degree of 131Cs concentration. However, the external counting method was not sensitive enough to warrant general application to patients with a suspected malignant tumor of the breast. False-positive breast study findings using radionuclides, such as 131CsCl, require close follow-up study in view of possible malignant changes in benign disease of the breast."} {"id": "PMID:181858", "title": "The role of cell receptors in tumor biology.", "content": "A general review of the role of receptors in tumor biology is presented. Nonhormonal receptors on the normal cells of the host are extremely important in the attempts to discern the origin and role of similar receptors on malignant cells. The most intriguing of these receptors is the Fc receptor which, in many respects, seems identical to the Fc receptor on B lymphocytes and macrophages. Recent data suggest chemical means of differentiating the Fc receptor of malignant cells from normal cells of the milieu. Such data are essential to resolve a controversy of the significance of the receptor and to help define the role of the receptor in the biology of tumors.", "contents": "The role of cell receptors in tumor biology. A general review of the role of receptors in tumor biology is presented. Nonhormonal receptors on the normal cells of the host are extremely important in the attempts to discern the origin and role of similar receptors on malignant cells. The most intriguing of these receptors is the Fc receptor which, in many respects, seems identical to the Fc receptor on B lymphocytes and macrophages. Recent data suggest chemical means of differentiating the Fc receptor of malignant cells from normal cells of the milieu. Such data are essential to resolve a controversy of the significance of the receptor and to help define the role of the receptor in the biology of tumors."} {"id": "PMID:181861", "title": "Hypersensitivity pneumonitis after exposure to isocyanates.", "content": "Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome.", "contents": "Hypersensitivity pneumonitis after exposure to isocyanates. Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome."} {"id": "PMID:181862", "title": "Bronchial adenoma: review of 18-year experience at the Brompton Hospital.", "content": "Continued uncertainty about the prognosis for patients with bronchial adenomata led to a review of the experience of this condition in the Brompton Hospital. Of 72 patients seen between January 1955 and December 1972, 39 were women and 33 men, mean age 45 years, range 9-73 years. The commonest presenting symptoms were haemoptysis, cough, sputum, and repeated chest infections. Positive bronchoscopic biopsy occurred in 35 of 43 cases; five of these were originally reported as carcinomata, of oat-cell type in four. Plain chest film abnormality occurred in 69 patients. Seventy-three operative procedures comprised two endoscopic removals, two wedge resections, six bronchotomies, five pneumonectomies, and 58 lobectomies (seven with sleeve resection). Recurrence in three of six bronchotomies--two with adenoid cystic carcinomata (cylindromata)--necessitated further surgery. Lobectomy and lymph node dissection is usually the operation of choice. Histology confirmed 67 carcinoids (eight with atypical histology or lymph node metastases), two adenoid cystic carcinomata, one muco-epidermoid, and two mucous gland adenomata. Prolonged follow-up is especially indicated in patients with adenoid cyst carcinoma and in those with atypical or metastatic carcinoid histology. Although such pathology is not incompatible with long survival, of 10 patients in these categories, all five late deaths were probably related to the tumour. However, of 57 patients considered to have had typical carcinoid histology and adequate removal of the tumour, there has to date been no tumour-related death, but one patient developed radiosensitive atypical carcinoid tracheal tumours nine years later. The actuarially assessed survival of 71 patients undergoing surgery for bronchial adenomata was 75% at 15 years. Specific tumour types should replace the term bronchial adenoma.", "contents": "Bronchial adenoma: review of 18-year experience at the Brompton Hospital. Continued uncertainty about the prognosis for patients with bronchial adenomata led to a review of the experience of this condition in the Brompton Hospital. Of 72 patients seen between January 1955 and December 1972, 39 were women and 33 men, mean age 45 years, range 9-73 years. The commonest presenting symptoms were haemoptysis, cough, sputum, and repeated chest infections. Positive bronchoscopic biopsy occurred in 35 of 43 cases; five of these were originally reported as carcinomata, of oat-cell type in four. Plain chest film abnormality occurred in 69 patients. Seventy-three operative procedures comprised two endoscopic removals, two wedge resections, six bronchotomies, five pneumonectomies, and 58 lobectomies (seven with sleeve resection). Recurrence in three of six bronchotomies--two with adenoid cystic carcinomata (cylindromata)--necessitated further surgery. Lobectomy and lymph node dissection is usually the operation of choice. Histology confirmed 67 carcinoids (eight with atypical histology or lymph node metastases), two adenoid cystic carcinomata, one muco-epidermoid, and two mucous gland adenomata. Prolonged follow-up is especially indicated in patients with adenoid cyst carcinoma and in those with atypical or metastatic carcinoid histology. Although such pathology is not incompatible with long survival, of 10 patients in these categories, all five late deaths were probably related to the tumour. However, of 57 patients considered to have had typical carcinoid histology and adequate removal of the tumour, there has to date been no tumour-related death, but one patient developed radiosensitive atypical carcinoid tracheal tumours nine years later. The actuarially assessed survival of 71 patients undergoing surgery for bronchial adenomata was 75% at 15 years. Specific tumour types should replace the term bronchial adenoma."} {"id": "PMID:181863", "title": "Cancer of the lung in women.", "content": "A study from Wales of 132 women with cancer of the lung admitted consecutively during the five years 1964-68, and of 13 other women submitted to surgery at an earlier period, showed that the prognosis for women was worse than for men. Every woman except one was followed up for more than five years. Of the 132 women in the consecutive series only five survived for five years, while the five-year survival rate after resection in 35 women was less than one-half of that of men. The cause of the worse prognosis for women in Wales appears to be due to some sex-linked factor. It cannot be explained by the age of the patient or by the histology, location, early or resectability of the growth. The prognosis of cancer of the lung in English, French, and American women is considered. The relative incidence of the disease in women and men is discussed. Sex and nationality appear to be of importance, but the influence of tobacco and other atmospheric carcinogens is obscure.", "contents": "Cancer of the lung in women. A study from Wales of 132 women with cancer of the lung admitted consecutively during the five years 1964-68, and of 13 other women submitted to surgery at an earlier period, showed that the prognosis for women was worse than for men. Every woman except one was followed up for more than five years. Of the 132 women in the consecutive series only five survived for five years, while the five-year survival rate after resection in 35 women was less than one-half of that of men. The cause of the worse prognosis for women in Wales appears to be due to some sex-linked factor. It cannot be explained by the age of the patient or by the histology, location, early or resectability of the growth. The prognosis of cancer of the lung in English, French, and American women is considered. The relative incidence of the disease in women and men is discussed. Sex and nationality appear to be of importance, but the influence of tobacco and other atmospheric carcinogens is obscure."} {"id": "PMID:181864", "title": "[Aujezky's disease in the field and vaccination against the disease (author's transl)].", "content": "A rather extensive outbreak of Aujeszky's disease in the area served by the above veterinarians is reported. Of 252 pig-breeding farms, eighty-two were contaminated. The other herds (170) were partly (81) vaccinated against the disease with the Bartha strain. Unlike de non-vaccinated group, the immunized herds showed few of any losses. In view of this fact it is concluded that Aujeszky's disease vaccination is a useful procedure (even in a contaminated environment).", "contents": "[Aujezky's disease in the field and vaccination against the disease (author's transl)]. A rather extensive outbreak of Aujeszky's disease in the area served by the above veterinarians is reported. Of 252 pig-breeding farms, eighty-two were contaminated. The other herds (170) were partly (81) vaccinated against the disease with the Bartha strain. Unlike de non-vaccinated group, the immunized herds showed few of any losses. In view of this fact it is concluded that Aujeszky's disease vaccination is a useful procedure (even in a contaminated environment)."} {"id": "PMID:181866", "title": "Effects of epinephrine and theophylline on lipolytic response in hereditary diabetic mice.", "content": "In non-obese but diabetic 15-week-old KK mice which showed fatty liver histopathologically, the content of liver lipids and the levels of blood glucose and plasma IRI were greater than those in the control ICR mice of the same age and were quite similar to those in GTG-obese mice. In 6-week-old KK mice which excreted no glycosuria and showed normal hepatic tissues, only plasma IRI level was slightly elevated as compared with that in the control mice. The cyclic 3',5'-AMP stimulators like epinephrine and theophylline exerted far less potent stimulatory effects on lipolytic activity in 6-week-old KK mice than in the control mice, as in diabetic 15-week-old KK mice and GTG-obese mice. Theophylline potentiated the lipolytic effect of epinephrine lineraly in KK mice, the tendency being different from that in the control mice, and only the submaximal rate was obtained. Furthermore, the inhibitory effect of theophylline on PDE from the epididymal adipose tissue was less potent in 6-week-old KK mice than in healthy ICR mice of the same age.", "contents": "Effects of epinephrine and theophylline on lipolytic response in hereditary diabetic mice. In non-obese but diabetic 15-week-old KK mice which showed fatty liver histopathologically, the content of liver lipids and the levels of blood glucose and plasma IRI were greater than those in the control ICR mice of the same age and were quite similar to those in GTG-obese mice. In 6-week-old KK mice which excreted no glycosuria and showed normal hepatic tissues, only plasma IRI level was slightly elevated as compared with that in the control mice. The cyclic 3',5'-AMP stimulators like epinephrine and theophylline exerted far less potent stimulatory effects on lipolytic activity in 6-week-old KK mice than in the control mice, as in diabetic 15-week-old KK mice and GTG-obese mice. Theophylline potentiated the lipolytic effect of epinephrine lineraly in KK mice, the tendency being different from that in the control mice, and only the submaximal rate was obtained. Furthermore, the inhibitory effect of theophylline on PDE from the epididymal adipose tissue was less potent in 6-week-old KK mice than in healthy ICR mice of the same age."} {"id": "PMID:181867", "title": "Experimental study of dibutyryl cyclic AMP: its antishock effects observed in traumatic shock rats.", "content": "Antishock effect of N6, O2-dibutyryl cyclic AMP (DBcAMP) Was investigated in rats subjected to Noble-Collip drum trauma and compared with effects of hydrocortisone and Trasylol. Results obtained are as follows. 1)Hydrocortisone and Trasylol administered 1 hr before initiating drumming improved the survival rate from traumatic shock with concomitant reducton of levels of acid phosphatase and beta-glucuronidase in circulating blood. DBcAMP administered i.p. immediately after trauma also improved the survival rate to the same extent as did Traylol or hydrocortisone, while no inhibitory effects were observed on acid phosphatase and beta-glucuronidase. 2)The rectal temperature fell significantly after suffering trauma, and the rats with greater fall in rectal temperature had poorer chance for survival. The fall in rectal temperature was considerably prevented by DBcAMP in a dose of 0.5 mg/100 g body weight (b.w.). 3)DBcAMP induced a rise in plasma insulin level (IRI) and insulin/glucose ratio (I/G) in shock rats, and the elevation in blood lactate/pyruvate ratio (L/P) and excess lactate otherwise observed after trauma were satisfactorily prevented by DBcAMP administration. It is concluded that the antichock effects of DBcAMP primarily resulted from improvements of the intracellular metabolism induced by its easy passage through the cell membrane and its cAMP like action, while any preventive action was not observed against elevation of lysosomal enzymes in the circulating blood.", "contents": "Experimental study of dibutyryl cyclic AMP: its antishock effects observed in traumatic shock rats. Antishock effect of N6, O2-dibutyryl cyclic AMP (DBcAMP) Was investigated in rats subjected to Noble-Collip drum trauma and compared with effects of hydrocortisone and Trasylol. Results obtained are as follows. 1)Hydrocortisone and Trasylol administered 1 hr before initiating drumming improved the survival rate from traumatic shock with concomitant reducton of levels of acid phosphatase and beta-glucuronidase in circulating blood. DBcAMP administered i.p. immediately after trauma also improved the survival rate to the same extent as did Traylol or hydrocortisone, while no inhibitory effects were observed on acid phosphatase and beta-glucuronidase. 2)The rectal temperature fell significantly after suffering trauma, and the rats with greater fall in rectal temperature had poorer chance for survival. The fall in rectal temperature was considerably prevented by DBcAMP in a dose of 0.5 mg/100 g body weight (b.w.). 3)DBcAMP induced a rise in plasma insulin level (IRI) and insulin/glucose ratio (I/G) in shock rats, and the elevation in blood lactate/pyruvate ratio (L/P) and excess lactate otherwise observed after trauma were satisfactorily prevented by DBcAMP administration. It is concluded that the antichock effects of DBcAMP primarily resulted from improvements of the intracellular metabolism induced by its easy passage through the cell membrane and its cAMP like action, while any preventive action was not observed against elevation of lysosomal enzymes in the circulating blood."} {"id": "PMID:181868", "title": "An outbreak of epidemic keratoconjunctivitis due to adenovirus type 8 in a babies home.", "content": "Between October and December, 1973, an outbreak of epidemic keratoconjunctivitis occurred in a babies home in Sapporo. 28 out of 58 infants and children suffered from the disease. Infection seemed to have been transmitted within a room by hands of nursing staff with spread into other rooms through the dispensary. Clinical manifestation in almost all of the patients was pseudomembraneous conjunctivitis without apparent corneal opacities. None of them showed systemic symptoms. Virus isolation was attempted from eye swabs of 4 patients between 5 and 8 days after onset of the disease, and adenovirus type 8 was isolated from all of the specimens. It was found that there was no case of subclinical infection by the serologic tests. Consecutive serologic studies revealed a good neutralizing antibody response to adenovirus type 8 in the patients tested.", "contents": "An outbreak of epidemic keratoconjunctivitis due to adenovirus type 8 in a babies home. Between October and December, 1973, an outbreak of epidemic keratoconjunctivitis occurred in a babies home in Sapporo. 28 out of 58 infants and children suffered from the disease. Infection seemed to have been transmitted within a room by hands of nursing staff with spread into other rooms through the dispensary. Clinical manifestation in almost all of the patients was pseudomembraneous conjunctivitis without apparent corneal opacities. None of them showed systemic symptoms. Virus isolation was attempted from eye swabs of 4 patients between 5 and 8 days after onset of the disease, and adenovirus type 8 was isolated from all of the specimens. It was found that there was no case of subclinical infection by the serologic tests. Consecutive serologic studies revealed a good neutralizing antibody response to adenovirus type 8 in the patients tested."} {"id": "PMID:181869", "title": "Difference between effects of conjugated estrogen on neurotics and non-neurotics of climacteric women complaining of menopausal symptoms and its clinical application for their screening.", "content": "In order to screen the neurotics and non-neurotics of climacteric women with menopausal symptoms, conjugated estrogen was injected intravenously and the reactions were compared. Menopausal symptoms were represented by Kupperman's menopausal index. After estrogen injection the non-neurotics showed a decrease of the index, i.e., alleviation of the symptoms, while the neurotics showed no change of the index. Taking advantage of this difference, a discriminant function between neurotics and non-neurotics was calculated using, as variables, Kupperman's menopasual indices determined before and after administration of the conjugated estrogen. The calculative screening obtained from this discriminant function yielded consistency with clinical diagnosis in about 94% of the neurotics and about 87% of the non-neurotics, suggesting that this test is of value in the screening of neurotics and non-neurotics in the climacteric women with menopausal symptoms.", "contents": "Difference between effects of conjugated estrogen on neurotics and non-neurotics of climacteric women complaining of menopausal symptoms and its clinical application for their screening. In order to screen the neurotics and non-neurotics of climacteric women with menopausal symptoms, conjugated estrogen was injected intravenously and the reactions were compared. Menopausal symptoms were represented by Kupperman's menopausal index. After estrogen injection the non-neurotics showed a decrease of the index, i.e., alleviation of the symptoms, while the neurotics showed no change of the index. Taking advantage of this difference, a discriminant function between neurotics and non-neurotics was calculated using, as variables, Kupperman's menopasual indices determined before and after administration of the conjugated estrogen. The calculative screening obtained from this discriminant function yielded consistency with clinical diagnosis in about 94% of the neurotics and about 87% of the non-neurotics, suggesting that this test is of value in the screening of neurotics and non-neurotics in the climacteric women with menopausal symptoms."} {"id": "PMID:181872", "title": "Effect of nafoxidine (U-11,100A) on the induction of uterine peroxidase.", "content": "The relationship between the quantity of nuclear estrogen receptor complex formed and the amount of peroxidase induced by estradiol in immature rat uteri was determined. A good correlation was obtained between the quantity of 3H-estradiol specifically bound to the nuclear pellet and the amount of enzyme present 12 h after treatment with physiological doses of estrogen. Nafoxidine (U-11,100A) administered together with estrogen reduced signficantly the increase in peroxidase activity brought about by estradiol. Pretreatment with nafoxidine was less effective. The possible mechanism of action of this antiestrogen is discussed.", "contents": "Effect of nafoxidine (U-11,100A) on the induction of uterine peroxidase. The relationship between the quantity of nuclear estrogen receptor complex formed and the amount of peroxidase induced by estradiol in immature rat uteri was determined. A good correlation was obtained between the quantity of 3H-estradiol specifically bound to the nuclear pellet and the amount of enzyme present 12 h after treatment with physiological doses of estrogen. Nafoxidine (U-11,100A) administered together with estrogen reduced signficantly the increase in peroxidase activity brought about by estradiol. Pretreatment with nafoxidine was less effective. The possible mechanism of action of this antiestrogen is discussed."} {"id": "PMID:181873", "title": "Inhibition of (3H) prostaglandin F2alpha binding to its receptors by progesterone.", "content": "The specific binding of [3H] prostaglandin (PG) F2alpha to bovine corpus luteum cell membranes was inhibited by progesterone. Progesterone inhibition of binding was dependent on membrane protein and independent of [3H] PGF2alpha concentrations in the medium. The lower inhibition of binding at high protein concentrations can be overcome by increasing the amounts of progesterone added. Progesterone inhibition of binding appears to be due to a decrease in the receptor number rather than a decrease in the receptor affinities. The kinetic properties (association and dissociation rates) of the remaining receptors were unchanged. The inhibition of [3H] PGF2alpha binding was observed by preincubating the membranes with progesterone or by adding at the beginning but not during incubation. The concentrations of progesterone that inhibited binding by about 50% do occur in bovine corpora lutea of estrous cycle and pregnancy.", "contents": "Inhibition of (3H) prostaglandin F2alpha binding to its receptors by progesterone. The specific binding of [3H] prostaglandin (PG) F2alpha to bovine corpus luteum cell membranes was inhibited by progesterone. Progesterone inhibition of binding was dependent on membrane protein and independent of [3H] PGF2alpha concentrations in the medium. The lower inhibition of binding at high protein concentrations can be overcome by increasing the amounts of progesterone added. Progesterone inhibition of binding appears to be due to a decrease in the receptor number rather than a decrease in the receptor affinities. The kinetic properties (association and dissociation rates) of the remaining receptors were unchanged. The inhibition of [3H] PGF2alpha binding was observed by preincubating the membranes with progesterone or by adding at the beginning but not during incubation. The concentrations of progesterone that inhibited binding by about 50% do occur in bovine corpora lutea of estrous cycle and pregnancy."} {"id": "PMID:181875", "title": "Clonorchiasis and hepatic neoplasms.", "content": "Thirty-eight subjects from Hong Kong with chronic infestation by Clonorchis sinensis were studied. Ten of the patients died of hepatocellular carcinoma, seven of cholangiocarcinoma, and one each of carcinoma of the common bile duct and lymphoma. The major difference between the patients having cholangiocarcinoma and hepatocellular carcinoma was cirrhosis. Only one patient with cholangiocarcinoma had cirrhosis; whereas all but one patient with hepatocellular carcinoma had cirrhosis. The etiopathogenesis of these two tumors is substantially different.", "contents": "Clonorchiasis and hepatic neoplasms. Thirty-eight subjects from Hong Kong with chronic infestation by Clonorchis sinensis were studied. Ten of the patients died of hepatocellular carcinoma, seven of cholangiocarcinoma, and one each of carcinoma of the common bile duct and lymphoma. The major difference between the patients having cholangiocarcinoma and hepatocellular carcinoma was cirrhosis. Only one patient with cholangiocarcinoma had cirrhosis; whereas all but one patient with hepatocellular carcinoma had cirrhosis. The etiopathogenesis of these two tumors is substantially different."} {"id": "PMID:181876", "title": "Hepatocellular carcinoma in the Gambia.", "content": "A hospital based study of hepatocellular carcinoma was undertaken in The Gambia. The overall male incidence rate was 12.0/100.000, almost certainly artificially low but putting The Gambia readily into the areas with a high incidence of this disease.", "contents": "Hepatocellular carcinoma in the Gambia. A hospital based study of hepatocellular carcinoma was undertaken in The Gambia. The overall male incidence rate was 12.0/100.000, almost certainly artificially low but putting The Gambia readily into the areas with a high incidence of this disease."} {"id": "PMID:181877", "title": "[Localization of several rhodopsin regeneration enzymes in retinal rods].", "content": "The distribution of NAD kinase and glucose-6-phosphate dehydrogenase within membranes of both outer and inner retina rod segments was studied by the sucrose gradient centrifugation of crude outer segment preparations. Rhodopsin and retinoldehydrogenase served as markers for outer segment membranes, whereas succinate dehydrogenase was a marker for inner ones. It is shown that NAD kinase and glucose-6-phosphate dehydrogenase are localized within inner segment membranes of the photoreception cell and that the activity of these enzymes in the crude preparations is due to contamination of the inner segments.", "contents": "[Localization of several rhodopsin regeneration enzymes in retinal rods]. The distribution of NAD kinase and glucose-6-phosphate dehydrogenase within membranes of both outer and inner retina rod segments was studied by the sucrose gradient centrifugation of crude outer segment preparations. Rhodopsin and retinoldehydrogenase served as markers for outer segment membranes, whereas succinate dehydrogenase was a marker for inner ones. It is shown that NAD kinase and glucose-6-phosphate dehydrogenase are localized within inner segment membranes of the photoreception cell and that the activity of these enzymes in the crude preparations is due to contamination of the inner segments."} {"id": "PMID:181878", "title": "[Synthesis of nicotinamide adenine dinucleotide in the nuclei of pigeon erythrocytes].", "content": "The nuclei of pigeon erythrocytes are capable of synthesizing NAD from nicotinamid-mononucleotides and ATP. Some data on the kinetics of NAD-pyrophosphorylase have been obtained: the optimal concentration of nuclei and the effect of various incubation time. The pretreatment of nuclei by Triton X-100, or by ultrasonics enhances NAD synthesis. The results suggest that cyclic 3',5'-AMP (Fluka) may have no effect on NAD synthesis. The control of the cell metabolism by NAD formation is considered.", "contents": "[Synthesis of nicotinamide adenine dinucleotide in the nuclei of pigeon erythrocytes]. The nuclei of pigeon erythrocytes are capable of synthesizing NAD from nicotinamid-mononucleotides and ATP. Some data on the kinetics of NAD-pyrophosphorylase have been obtained: the optimal concentration of nuclei and the effect of various incubation time. The pretreatment of nuclei by Triton X-100, or by ultrasonics enhances NAD synthesis. The results suggest that cyclic 3',5'-AMP (Fluka) may have no effect on NAD synthesis. The control of the cell metabolism by NAD formation is considered."} {"id": "PMID:181880", "title": "[Enzyme, electron microscopic and polarographic characteristics of isolated rat brain mitochondria. III. Quantitative assessment of their distribution in fractions of the homogenate].", "content": "Activities of succinate dehydrogenase, succinate- and NAD-H-cytochrome c--reductases, and cytochrome c--oxidase was compared in 1 g tissue homogenate and homogenate fractions made from 1 g brain tissue using various solutions. Fractionation resulted in the increased activities of NADH- and succinate cytochrome reductases, and in the loss of succinate dehydrogenase activity, cytochrome oxidase was less influenced. These phenomena are regarded as signs of the interrelation between mitochondria and other constituents of brain cell within homogenates. Maximal quantity of mitochondria isolated from homogenates is no more than 20% of all the mitochondrial homogenates (according enzyme data). The electronogram of the brain mitochondrial preparation isolated in the Krebs--Ringer solution without glucose pointed out to a high homogeneity of mitochondria in the residue.", "contents": "[Enzyme, electron microscopic and polarographic characteristics of isolated rat brain mitochondria. III. Quantitative assessment of their distribution in fractions of the homogenate]. Activities of succinate dehydrogenase, succinate- and NAD-H-cytochrome c--reductases, and cytochrome c--oxidase was compared in 1 g tissue homogenate and homogenate fractions made from 1 g brain tissue using various solutions. Fractionation resulted in the increased activities of NADH- and succinate cytochrome reductases, and in the loss of succinate dehydrogenase activity, cytochrome oxidase was less influenced. These phenomena are regarded as signs of the interrelation between mitochondria and other constituents of brain cell within homogenates. Maximal quantity of mitochondria isolated from homogenates is no more than 20% of all the mitochondrial homogenates (according enzyme data). The electronogram of the brain mitochondrial preparation isolated in the Krebs--Ringer solution without glucose pointed out to a high homogeneity of mitochondria in the residue."} {"id": "PMID:181882", "title": "[The effect of ultraviolet radiation of different wave lengths on the concentration of DNA--fuchsin in the cells of Zajdel's ascitic hepatoma].", "content": "The cytophotometrical analysis of the relationships between the content of DNA--fuchsin and the duration of acid hydrolysis of the intranuclear DNA (the Feulgen reaction) in the Zaidela hepatoma cells allows to see the degree of the DNA--protein binding. The UV irradiation of different wave-lengths (254, 325 and 365 nm, resp.) irrespective of the degree of absorption by nucleic acids, causes changes in chromatin condensation, thus suggesting the labilization of DNA--protein bounds.", "contents": "[The effect of ultraviolet radiation of different wave lengths on the concentration of DNA--fuchsin in the cells of Zajdel's ascitic hepatoma]. The cytophotometrical analysis of the relationships between the content of DNA--fuchsin and the duration of acid hydrolysis of the intranuclear DNA (the Feulgen reaction) in the Zaidela hepatoma cells allows to see the degree of the DNA--protein binding. The UV irradiation of different wave-lengths (254, 325 and 365 nm, resp.) irrespective of the degree of absorption by nucleic acids, causes changes in chromatin condensation, thus suggesting the labilization of DNA--protein bounds."} {"id": "PMID:181886", "title": "Fasting urine excretion of magnesium, calcium, and sodium in patients with renal calcium stones.", "content": "Urine excretion of magnesium (Mg), calcium (Ca) and sodium(Na) was studied in patients with renal Ca stones having normal kidney function (n= 60), and in matched controls (n= 60), on a free diet following an overnight fasting period. In some formers, Mg was lower than in normals, whereas Ca was unusually high resulting in a significantly higher molar Ca/Mg ratio (p less than 0.001). 2. In 3 out of 4 stone groups Na excretion was significantly elevated because of reduced tubular reabsorption. In normals, fractional Na excretion varied between 0.44 and 0.54% of endogenous creatinine clearance, whereas it exceeded 1% in the stone patients. Conversely, the molar ratio Na/Ca was equal in all groups. 3. Fasting urinary cyclic AMP was comparable in both populations supporting the assumption that in the majority of patients Ca- or Mg- wasting via urine may not be responsible for secondary hyperparathyroidism. In small selected groups, losses of divalent cations may act in concert, leading to stimulation of the parathyroid glands. 4. Correlations between minerals and Na reveal a close relationship between Na, Ca and Mg in terms of clearance and excretion rate in patients and controls. Fractional Na and Ca excretion are correlated in patients but not in normals. This suggests that in the absence of phosphaturia, factors other than extracellular volume expansion and/or hyperparathyroidism are operative in stone disease. 5. The origin of fasting natriuresis and relative hypercalciuria may be ascribed to a change, as yet not causally identified, in distal tubular Na reabsorption.", "contents": "Fasting urine excretion of magnesium, calcium, and sodium in patients with renal calcium stones. Urine excretion of magnesium (Mg), calcium (Ca) and sodium(Na) was studied in patients with renal Ca stones having normal kidney function (n= 60), and in matched controls (n= 60), on a free diet following an overnight fasting period. In some formers, Mg was lower than in normals, whereas Ca was unusually high resulting in a significantly higher molar Ca/Mg ratio (p less than 0.001). 2. In 3 out of 4 stone groups Na excretion was significantly elevated because of reduced tubular reabsorption. In normals, fractional Na excretion varied between 0.44 and 0.54% of endogenous creatinine clearance, whereas it exceeded 1% in the stone patients. Conversely, the molar ratio Na/Ca was equal in all groups. 3. Fasting urinary cyclic AMP was comparable in both populations supporting the assumption that in the majority of patients Ca- or Mg- wasting via urine may not be responsible for secondary hyperparathyroidism. In small selected groups, losses of divalent cations may act in concert, leading to stimulation of the parathyroid glands. 4. Correlations between minerals and Na reveal a close relationship between Na, Ca and Mg in terms of clearance and excretion rate in patients and controls. Fractional Na and Ca excretion are correlated in patients but not in normals. This suggests that in the absence of phosphaturia, factors other than extracellular volume expansion and/or hyperparathyroidism are operative in stone disease. 5. The origin of fasting natriuresis and relative hypercalciuria may be ascribed to a change, as yet not causally identified, in distal tubular Na reabsorption."} {"id": "PMID:181883", "title": "[Peptide hydrolase activity of different sections of the rat brain].", "content": "The protamine-splitting peptid hydrolase activity method was modified for using when analyzing the different areas of the rat brain. The tissue weight was 15-40 mg, only 3.5 mg was sufficient for investigation in a test tube. The indexes of neutral peptide hydrolase activity differed thrice and were arranged as follows: auditory and optic cortex--41, cerebellum--60, hypothalamic area and corpus striatum--69, hippocamp--89, corpora quadrigemina--92, pyramides and pons--120, medula--121, and thalamus--122, The deprivation of REM-sleep for 24 and 48 hours or total sleep deprivation for 24 hours did not cause changes in the peptide-hydrolase activity of the investigated brain areas.", "contents": "[Peptide hydrolase activity of different sections of the rat brain]. The protamine-splitting peptid hydrolase activity method was modified for using when analyzing the different areas of the rat brain. The tissue weight was 15-40 mg, only 3.5 mg was sufficient for investigation in a test tube. The indexes of neutral peptide hydrolase activity differed thrice and were arranged as follows: auditory and optic cortex--41, cerebellum--60, hypothalamic area and corpus striatum--69, hippocamp--89, corpora quadrigemina--92, pyramides and pons--120, medula--121, and thalamus--122, The deprivation of REM-sleep for 24 and 48 hours or total sleep deprivation for 24 hours did not cause changes in the peptide-hydrolase activity of the investigated brain areas."} {"id": "PMID:181884", "title": "[Differences in the enzymatic activity of mitochondria from enriched neuronal and glial fractions].", "content": "Studies were performed in the activities of certain enzymes from oxidoreductase group: cytochrome c-oxidoreductase (EC 1.6.99.3), succinate dehydrogenase succinates: cytochrome c-oxidoreductase (EC 1.3.99.1), cytochrome oxidase (EC 1.9.3.1) and malate dehydrogenase (EC 1.1.1.37) in mitochondria from neuronal and glial-enriched fractions. The mitochondrial fraction purity was observed by the electron microscope. The enzyme activity of the glial mitochondrial fraction was much higher than that in the neuronal mitochondria. Malate dehydrogenase from glial enriched fraction consists of three isoenzymes, while neuronal mitochondria had two isoenzymes of malate dehydrogenase. The neuronal mitochondria were found to be more stable to lubrol and digitonin.", "contents": "[Differences in the enzymatic activity of mitochondria from enriched neuronal and glial fractions]. Studies were performed in the activities of certain enzymes from oxidoreductase group: cytochrome c-oxidoreductase (EC 1.6.99.3), succinate dehydrogenase succinates: cytochrome c-oxidoreductase (EC 1.3.99.1), cytochrome oxidase (EC 1.9.3.1) and malate dehydrogenase (EC 1.1.1.37) in mitochondria from neuronal and glial-enriched fractions. The mitochondrial fraction purity was observed by the electron microscope. The enzyme activity of the glial mitochondrial fraction was much higher than that in the neuronal mitochondria. Malate dehydrogenase from glial enriched fraction consists of three isoenzymes, while neuronal mitochondria had two isoenzymes of malate dehydrogenase. The neuronal mitochondria were found to be more stable to lubrol and digitonin."} {"id": "PMID:181890", "title": "[Study of leukocytic enzymes in patients with diffuse peritonitis].", "content": "Under observation were 25 patients with grave diffuse peritonitis. Histochemically, the activity of oxidation-reduction enzymes in leukocytes of peripheral blood was determined. It was found that the control of enzymic activity at the cellular level and determination of the concentration of lactic and pyruvic acids permitted the detection of hypoxic alterations in peritonitis, provided an opportunity to judge the dynamics of the pathological process.", "contents": "[Study of leukocytic enzymes in patients with diffuse peritonitis]. Under observation were 25 patients with grave diffuse peritonitis. Histochemically, the activity of oxidation-reduction enzymes in leukocytes of peripheral blood was determined. It was found that the control of enzymic activity at the cellular level and determination of the concentration of lactic and pyruvic acids permitted the detection of hypoxic alterations in peritonitis, provided an opportunity to judge the dynamics of the pathological process."} {"id": "PMID:181885", "title": "[Determination of the content of biogenic amines and their precursors by a thin-layer chromatographic method].", "content": "A method is developed for a simultaneous determination of the content of biogenic phenyl- and indolalkylamines and their predecessors. The method includes preparation of a homogenate by cutting the animal tissue and its extraction in acidic butanol, purification of butanol from tissue by centrifugation, subsequent conversion of the substances from the alcohol phase to the aqueous one and lyophilization of the latter. Then thin layer chromatography is performed. For obtaining the neutral separating layer the mixture of the microcyrstalline cellulose JIT and silicagel is used. The mixture ethyl acetate--acetic acid--water (5:1.5:1.5) is used as a solvent. The thin layers of cellulose JIT or ecteolo-cellulose with the solvent 0.01-n HC1 and cellulose JIT with the solvent ethyl acetate--acetic acid-water (5:1.5:1.5) may be used, respectively, for determining the content of the reactions final products, when measuring the enzymic activities of DOPA-decarboxylase and 5-oxytryptophan-decarboxylase.", "contents": "[Determination of the content of biogenic amines and their precursors by a thin-layer chromatographic method]. A method is developed for a simultaneous determination of the content of biogenic phenyl- and indolalkylamines and their predecessors. The method includes preparation of a homogenate by cutting the animal tissue and its extraction in acidic butanol, purification of butanol from tissue by centrifugation, subsequent conversion of the substances from the alcohol phase to the aqueous one and lyophilization of the latter. Then thin layer chromatography is performed. For obtaining the neutral separating layer the mixture of the microcyrstalline cellulose JIT and silicagel is used. The mixture ethyl acetate--acetic acid--water (5:1.5:1.5) is used as a solvent. The thin layers of cellulose JIT or ecteolo-cellulose with the solvent 0.01-n HC1 and cellulose JIT with the solvent ethyl acetate--acetic acid-water (5:1.5:1.5) may be used, respectively, for determining the content of the reactions final products, when measuring the enzymic activities of DOPA-decarboxylase and 5-oxytryptophan-decarboxylase."} {"id": "PMID:181891", "title": "Serological study of an outbreak of paresis due to equid herpesvirus 1 (EHV-1).", "content": "Six cases of paresis occurred in a Swedish stud with 48 mares and a stallion. Complement-fixation tests revealed a recent infection with EHV-1 in most horses of the stud. Serumneutralisation tests showed rapid antibody-titre increases during the course of the disease. This type of antibody response was interpreted as induced by reinfection or, possibly, recurrent infection. Two diseased mares were sacrificed. No virus could be isolated from their central nervous system (CNS), liver or spleen, but there is a presumptive evidence for the presence of an antigen specific to EHV-1 in the CNS and liver. Neutralising antibodies to EHV-1 were demonstrated in the liver and kidneys following elution by acidification of the tissues. No such antibodies could be demonstrated in the brain and spinal cord. A possible reason for this failure is discussed.", "contents": "Serological study of an outbreak of paresis due to equid herpesvirus 1 (EHV-1). Six cases of paresis occurred in a Swedish stud with 48 mares and a stallion. Complement-fixation tests revealed a recent infection with EHV-1 in most horses of the stud. Serumneutralisation tests showed rapid antibody-titre increases during the course of the disease. This type of antibody response was interpreted as induced by reinfection or, possibly, recurrent infection. Two diseased mares were sacrificed. No virus could be isolated from their central nervous system (CNS), liver or spleen, but there is a presumptive evidence for the presence of an antigen specific to EHV-1 in the CNS and liver. Neutralising antibodies to EHV-1 were demonstrated in the liver and kidneys following elution by acidification of the tissues. No such antibodies could be demonstrated in the brain and spinal cord. A possible reason for this failure is discussed."} {"id": "PMID:181894", "title": "[Agar gel diffusion precipitation and immunoelectrophoresis of the Aujeszky virus].", "content": "Two virulent and two vaccinal virus strains are dealt with. The study has been carried out by means of the diffusion precipitation reaction in agar gel and the immunoelectrophoresis technique using hyperimmune sera obtained from cocks as well as concentrated and purified antigens. It has been demonstrated that the virulent and the vaccinal (latent) strains of Aujeszky's disease virus cannot be differentiated serologically. The complex of antibodies induced by the virulent and the latent strains has proved to contain absolutely identical products. On the basis of the results obtained it is suggested to find some other means (markers) to differentiate the virulent from the latent strains of the virus.", "contents": "[Agar gel diffusion precipitation and immunoelectrophoresis of the Aujeszky virus]. Two virulent and two vaccinal virus strains are dealt with. The study has been carried out by means of the diffusion precipitation reaction in agar gel and the immunoelectrophoresis technique using hyperimmune sera obtained from cocks as well as concentrated and purified antigens. It has been demonstrated that the virulent and the vaccinal (latent) strains of Aujeszky's disease virus cannot be differentiated serologically. The complex of antibodies induced by the virulent and the latent strains has proved to contain absolutely identical products. On the basis of the results obtained it is suggested to find some other means (markers) to differentiate the virulent from the latent strains of the virus."} {"id": "PMID:181895", "title": "[Effectiveness of a Bulgarian vaccine against Marek's disease in broilers].", "content": "Studies were carried out to establish the effectiveness of the immunization of broilers against Marek's disease using a Bulgarian vaccine produced with strain C3-1 of a turkey herpes virus. The experiments were done under the conditions of an industrial poultry dressing combine with a total of 52,450 day-old hybrid birds vaccinated at the rate of 1000 plaque-forming units (PFU), 39,450 birds vaccinated with 500 PFU each, and 91,564 unvaccinated control birds. After the 60-63-day fattening period was over the average value of the mortality rate was 2.17 per cent and 2.48 per cent in the vaccinated birds and the controls, respectively. The vaccinated groups of birds showed also a comparatively higher weight gain--by 73 g, on an average, recorded prior to slaughter--as against the control groups. No differences were found in these indices between the groups immunized with 1000 and 500 PFU. In a laboratory test with 255 birds divided into four groups immunized with 100, 500, 250, PFU and controls, challenged in the third week with a pathogenic herpes virus it was found that up to the 6th month the first two groups developed Marek's disease as accounted by 1.65 per cent of the birds, while those vaccinated at the rate of 250 PFU were not properly protected, showing a higher morbidity rate--9.23 per cent. It is concluded that the Bulgarian vaccine--strain C3-1--confers solid immunity in a dose of 500 PFU, the vaccination of broilers being economically profitable.", "contents": "[Effectiveness of a Bulgarian vaccine against Marek's disease in broilers]. Studies were carried out to establish the effectiveness of the immunization of broilers against Marek's disease using a Bulgarian vaccine produced with strain C3-1 of a turkey herpes virus. The experiments were done under the conditions of an industrial poultry dressing combine with a total of 52,450 day-old hybrid birds vaccinated at the rate of 1000 plaque-forming units (PFU), 39,450 birds vaccinated with 500 PFU each, and 91,564 unvaccinated control birds. After the 60-63-day fattening period was over the average value of the mortality rate was 2.17 per cent and 2.48 per cent in the vaccinated birds and the controls, respectively. The vaccinated groups of birds showed also a comparatively higher weight gain--by 73 g, on an average, recorded prior to slaughter--as against the control groups. No differences were found in these indices between the groups immunized with 1000 and 500 PFU. In a laboratory test with 255 birds divided into four groups immunized with 100, 500, 250, PFU and controls, challenged in the third week with a pathogenic herpes virus it was found that up to the 6th month the first two groups developed Marek's disease as accounted by 1.65 per cent of the birds, while those vaccinated at the rate of 250 PFU were not properly protected, showing a higher morbidity rate--9.23 per cent. It is concluded that the Bulgarian vaccine--strain C3-1--confers solid immunity in a dose of 500 PFU, the vaccination of broilers being economically profitable."} {"id": "PMID:181896", "title": "[Experimental infection with bovid herpesvirus 2].", "content": "An experimental infection with strain KOS/Haskovo of the Bovid Herpesvirus 2, isolated in Bulgaria, was induced in susceptible heifers through intradermal, intranasal, and intravenous application. Regardless of the route of infection clinically the disease manifested itself as an eczema of an urticarial type, accompanied by a febrile reaction, leukopenia, erythropenia, and oligochromemia. Highest titers of virus-neutralizing antibodies were established on the 30th day following infection in the i/v injected animals. All experimentally infected animals remained resistant to a challenge with a homologous virus on the 80th day after they were infected.", "contents": "[Experimental infection with bovid herpesvirus 2]. An experimental infection with strain KOS/Haskovo of the Bovid Herpesvirus 2, isolated in Bulgaria, was induced in susceptible heifers through intradermal, intranasal, and intravenous application. Regardless of the route of infection clinically the disease manifested itself as an eczema of an urticarial type, accompanied by a febrile reaction, leukopenia, erythropenia, and oligochromemia. Highest titers of virus-neutralizing antibodies were established on the 30th day following infection in the i/v injected animals. All experimentally infected animals remained resistant to a challenge with a homologous virus on the 80th day after they were infected."} {"id": "PMID:181897", "title": "[Study of the immunogenic properties of inactivated vaccines prepared with the infectious bovine rhinotracheitis virus (IBR)].", "content": "Tested were the chemical and physico-chemical means for the inactivation of the infectious bovine rhinotracheitis virus. Formalin and saponin were shown to decrease the immunogenic activity of the virus. The inactivation of the virus, preserving its immunogenic properties, was achieved with the use of two inactivating factors (1 and 2), and the concentrated vaccines produced containing an oil adjuvant at amounts of 10 cu. cm per dose in the vaccination and revaccination at a 28-day interval proved highly immunogenic. Neutralizing antibodies in the vaccinated rabbits and calves were demonstrated after the 14th day following treatment. The antibody titers on the 28th day following vaccination, and on the 14th day following revaccination reached their peak levels: log 2.5 to 4.5 and 6.5 to 7.5, respectively. The problem is discussed of the correlation between the circulation and the secretory neutralizing antibodies after immunization with an inactivated IBR vaccine.", "contents": "[Study of the immunogenic properties of inactivated vaccines prepared with the infectious bovine rhinotracheitis virus (IBR)]. Tested were the chemical and physico-chemical means for the inactivation of the infectious bovine rhinotracheitis virus. Formalin and saponin were shown to decrease the immunogenic activity of the virus. The inactivation of the virus, preserving its immunogenic properties, was achieved with the use of two inactivating factors (1 and 2), and the concentrated vaccines produced containing an oil adjuvant at amounts of 10 cu. cm per dose in the vaccination and revaccination at a 28-day interval proved highly immunogenic. Neutralizing antibodies in the vaccinated rabbits and calves were demonstrated after the 14th day following treatment. The antibody titers on the 28th day following vaccination, and on the 14th day following revaccination reached their peak levels: log 2.5 to 4.5 and 6.5 to 7.5, respectively. The problem is discussed of the correlation between the circulation and the secretory neutralizing antibodies after immunization with an inactivated IBR vaccine."} {"id": "PMID:181898", "title": "[Action of rifampicin on the reproduction of Aujeszky's disease virus].", "content": "The study on the effect of rifampicin on the reproduction of Aujeszky's disease virus (strains 2, 5, 7, 10, 12, and 17, which are virulent, and strain MK, which is an avirulent virus mutant) in cell cultures revealed that the formation of plaques is inhibited, though to a slighter extent, at a concentration of the inhibiting agent of 100 mug/ml, the value of their titer lowering by one logarithm. All virus strains have proved equally susceptible to the effect of rifampicin. During the virus multiplication in the presence of rifampicin the diameter of the plaques formed decreases from 2.8 to 0.5 mm, and with the avirulent strain MK it decreases up to 0.2 mm. They have rose tint in contrast to the plaques formed by strain 2, which are colourless. Rifampicin has no effect on virus reproduction when the cells are cultivated 24 hours prior to adding the antibiotic or when the virus adsorption on the cells takes place simultaneously with rifampicin. At lower rates the latter does not alter the reproduction process of the virus, however, at doses higher than 10 mug/ml it becomes toxic for the cells. Rifampicin inhibits the multiplication of the virus if it is added to the infected cell cultures up to the 12th hour following the adsorption of the virus. When 25-diacetyl-rifampicin is added to the nutrient medium the number of the plaques formed decreases but no change in their diameter occurs. However, with the avirulent MK strain both the number of plaques and their size decreases. Rifampicin B and rifampicin SV have no effect on the reproduction of Aujeszky's disease virus.", "contents": "[Action of rifampicin on the reproduction of Aujeszky's disease virus]. The study on the effect of rifampicin on the reproduction of Aujeszky's disease virus (strains 2, 5, 7, 10, 12, and 17, which are virulent, and strain MK, which is an avirulent virus mutant) in cell cultures revealed that the formation of plaques is inhibited, though to a slighter extent, at a concentration of the inhibiting agent of 100 mug/ml, the value of their titer lowering by one logarithm. All virus strains have proved equally susceptible to the effect of rifampicin. During the virus multiplication in the presence of rifampicin the diameter of the plaques formed decreases from 2.8 to 0.5 mm, and with the avirulent strain MK it decreases up to 0.2 mm. They have rose tint in contrast to the plaques formed by strain 2, which are colourless. Rifampicin has no effect on virus reproduction when the cells are cultivated 24 hours prior to adding the antibiotic or when the virus adsorption on the cells takes place simultaneously with rifampicin. At lower rates the latter does not alter the reproduction process of the virus, however, at doses higher than 10 mug/ml it becomes toxic for the cells. Rifampicin inhibits the multiplication of the virus if it is added to the infected cell cultures up to the 12th hour following the adsorption of the virus. When 25-diacetyl-rifampicin is added to the nutrient medium the number of the plaques formed decreases but no change in their diameter occurs. However, with the avirulent MK strain both the number of plaques and their size decreases. Rifampicin B and rifampicin SV have no effect on the reproduction of Aujeszky's disease virus."} {"id": "PMID:181900", "title": "Fibrous histiocytoma simulating congenital fibromatosis: a light-, electron microscopic and tissue culture study.", "content": "The unusual occurrence of a fibrous histiocytoma of subcutaneous soft tissues, bones, and viscera is described in a newborn infant. The clinical and radiologic picture simulated a congenital fibromatosis, but histologic, electronmicroscopic and tissue culture studies indicated a malignant tumor with a bimodal cell population resembling immature fibroblasts and histiocytes. Although less mature and more uniform, it essentially parallels the findings in the adult malignant fibrous histiocytomas.", "contents": "Fibrous histiocytoma simulating congenital fibromatosis: a light-, electron microscopic and tissue culture study. The unusual occurrence of a fibrous histiocytoma of subcutaneous soft tissues, bones, and viscera is described in a newborn infant. The clinical and radiologic picture simulated a congenital fibromatosis, but histologic, electronmicroscopic and tissue culture studies indicated a malignant tumor with a bimodal cell population resembling immature fibroblasts and histiocytes. Although less mature and more uniform, it essentially parallels the findings in the adult malignant fibrous histiocytomas."} {"id": "PMID:181901", "title": "Ultrastructural and x-ray analytical studies on intranuclear bismuth inclusions.", "content": "Parenteral administration of bismuth subnitrate produced intranuclear inclusions in the rabbit kidney tubules. In glutaraldehyde fixed material these inclusions had a homogeneous appearance but in osmicated material some of these inclusions showed a granular and fibrillar substructure. In relatively thick unstained sections prepared from unosmicated tissues, it was found that the inclusions were electron-dense, but they vanished from view when the electron beam was focussed on them. This phenomenon is thought to be due to the presence of bismuth, which is a mental with a high electrical resistance and low thermal conductivity. With the aid of electron-probe analysis the presence of bismuth was demonstrated in these inclusions and it seems possible that sulphur may be present here.", "contents": "Ultrastructural and x-ray analytical studies on intranuclear bismuth inclusions. Parenteral administration of bismuth subnitrate produced intranuclear inclusions in the rabbit kidney tubules. In glutaraldehyde fixed material these inclusions had a homogeneous appearance but in osmicated material some of these inclusions showed a granular and fibrillar substructure. In relatively thick unstained sections prepared from unosmicated tissues, it was found that the inclusions were electron-dense, but they vanished from view when the electron beam was focussed on them. This phenomenon is thought to be due to the presence of bismuth, which is a mental with a high electrical resistance and low thermal conductivity. With the aid of electron-probe analysis the presence of bismuth was demonstrated in these inclusions and it seems possible that sulphur may be present here."} {"id": "PMID:181902", "title": "Cellular transformation in vitro induced by herpes simplex virus (HSV). Note III. Oncogenicity of some HSV-2-transformed cell lines.", "content": "At high in vitro passage levels HSV-2-transformed hamster and rat cell lines were oncogenic for the homologous animals, inducing fusocellular or round-cell sarcomas. The cell lines obtained by in vitro cultivation of the tumors were free of infectious virus.", "contents": "Cellular transformation in vitro induced by herpes simplex virus (HSV). Note III. Oncogenicity of some HSV-2-transformed cell lines. At high in vitro passage levels HSV-2-transformed hamster and rat cell lines were oncogenic for the homologous animals, inducing fusocellular or round-cell sarcomas. The cell lines obtained by in vitro cultivation of the tumors were free of infectious virus."} {"id": "PMID:181918", "title": "[Investigations on the prophylaxis of wound infection by the topical application of a combination of polymyxin-b, bacitracin and neomycin (polybactrin spray) (author's transl)].", "content": "A controlled prospective trial was carried out on 100 cases of appendicectomy for a suppurative or perforated apendix, 153 operations on the biliary tract and 25 abdominal colon and rectum resections. The topical administration of Polybactrin aerosol, sprayed once into the open laparotomy wound produced a significant reduction in postoperative wound infection.", "contents": "[Investigations on the prophylaxis of wound infection by the topical application of a combination of polymyxin-b, bacitracin and neomycin (polybactrin spray) (author's transl)]. A controlled prospective trial was carried out on 100 cases of appendicectomy for a suppurative or perforated apendix, 153 operations on the biliary tract and 25 abdominal colon and rectum resections. The topical administration of Polybactrin aerosol, sprayed once into the open laparotomy wound produced a significant reduction in postoperative wound infection."} {"id": "PMID:181919", "title": "[Prognostic assessment in peripheral facial nerve paralysis with particular reference to electroneurography (author's transl)].", "content": "Electrophysiological investigations were carried out on 20 healthy controls and 130 patients with peripheral facial nerve paralysis. The aetiology was as follows: idiopathic (Bell's palsy) in 60 cases, viral in 29, traumatic in 18, postoperative in 4, in connexion with chronic otitis media in 6, diabetes mellitus in 4, positive rheumatological tests in 3, disturbed lipid metabolism in 2, the Melkersson-Rosenthal syndrome in 1, as a complication of pregnancy in 2, and in association with a tumour in 1 case. The compound action potential (CAP) of the orbicularis oris muscle was determinedi n 370 occasions in a right/left comparision, the record of the muscle response was intergrated over the time of action (IAR) on 32 occasions and trison of 255 occasions. The normal values are given in the first place and their dependence of the age of the subject. Then, the prognostic sifnficance of the above-mentioned parameters is investigated in cases of peripheral facial nerve paralysis. It is apparent that the determination of the CAP in a right/left comparison is a valuable prognostic guide as early as the 4th day, insofar as a decrease in this parameter of under 50% can be interpreted as a favourable sign and satisfactory reversal of the paralysis can be expected within 6-8 weeks. By contrast, a decrease of over 70% in the CAP is a bad prognostic sign, indicative of presumably only a poor trend to reversal of the paralysis. An intermediate depression of the CAP in the range of 50-70% signifies an expected moderate recovery within 6-8 weeks ahe case of CAP determination at the time of maximum amplitude depression (as opposed to the 4th day), then a decrease of less than 70% is taken to be indicative of satisfactory functional recovery within 6-8 weeks; a decrease of 95-100% signifies a bad prognosis, whilst a decrease amounting to between 70 and 95% carries an uncertain prognosis. The maximum decrease in amplitude was registered on the 8th day on average; the range lay between the 4th and the 14th day. An exception to these figures was the delayed response of the CAP in the case of 6 patients, 5 of whom showed a maximum decrease during the 3rd week and the last patient as late as the 4th week following the onset of facial nerve paresis. Similar reliance can be placed on the prognostic value of the IAR. however, the decrease in the IAR is smaller than that of the CAP measured on the same potential in a right/left comparison, so that a decrease in the IAR of over 60% can already herald a poor recovery. Repeated determination of the latency in cases of facial nerve paralysis showed that the mean latency value for the entire group of patients was slightly prolonged at the end of the 1st week, but the latency values obtained in any one particular patient are of no prognostic significance. A comparison between CAP and latency values obtained with the opposite (i.e...", "contents": "[Prognostic assessment in peripheral facial nerve paralysis with particular reference to electroneurography (author's transl)]. Electrophysiological investigations were carried out on 20 healthy controls and 130 patients with peripheral facial nerve paralysis. The aetiology was as follows: idiopathic (Bell's palsy) in 60 cases, viral in 29, traumatic in 18, postoperative in 4, in connexion with chronic otitis media in 6, diabetes mellitus in 4, positive rheumatological tests in 3, disturbed lipid metabolism in 2, the Melkersson-Rosenthal syndrome in 1, as a complication of pregnancy in 2, and in association with a tumour in 1 case. The compound action potential (CAP) of the orbicularis oris muscle was determinedi n 370 occasions in a right/left comparision, the record of the muscle response was intergrated over the time of action (IAR) on 32 occasions and trison of 255 occasions. The normal values are given in the first place and their dependence of the age of the subject. Then, the prognostic sifnficance of the above-mentioned parameters is investigated in cases of peripheral facial nerve paralysis. It is apparent that the determination of the CAP in a right/left comparison is a valuable prognostic guide as early as the 4th day, insofar as a decrease in this parameter of under 50% can be interpreted as a favourable sign and satisfactory reversal of the paralysis can be expected within 6-8 weeks. By contrast, a decrease of over 70% in the CAP is a bad prognostic sign, indicative of presumably only a poor trend to reversal of the paralysis. An intermediate depression of the CAP in the range of 50-70% signifies an expected moderate recovery within 6-8 weeks ahe case of CAP determination at the time of maximum amplitude depression (as opposed to the 4th day), then a decrease of less than 70% is taken to be indicative of satisfactory functional recovery within 6-8 weeks; a decrease of 95-100% signifies a bad prognosis, whilst a decrease amounting to between 70 and 95% carries an uncertain prognosis. The maximum decrease in amplitude was registered on the 8th day on average; the range lay between the 4th and the 14th day. An exception to these figures was the delayed response of the CAP in the case of 6 patients, 5 of whom showed a maximum decrease during the 3rd week and the last patient as late as the 4th week following the onset of facial nerve paresis. Similar reliance can be placed on the prognostic value of the IAR. however, the decrease in the IAR is smaller than that of the CAP measured on the same potential in a right/left comparison, so that a decrease in the IAR of over 60% can already herald a poor recovery. Repeated determination of the latency in cases of facial nerve paralysis showed that the mean latency value for the entire group of patients was slightly prolonged at the end of the 1st week, but the latency values obtained in any one particular patient are of no prognostic significance. A comparison between CAP and latency values obtained with the opposite (i.e..."} {"id": "PMID:181922", "title": "Tumor inhibiting capacity of spleen and lymph node cells from mice with murine sarcoma virus (MSV-M)-induced tumors.", "content": "The direct tumor inhibiting capacity of spleen and lymph node cells obtained from mice in different stages of Moloney sarcoma virus (MSV-M)-induced tumor development was studied. MSV-M producing ascitic tumor cells with a tumor dosis50 of about 10(3) cells and a mean latent period--depending on the amount of transplanted cells--of6-12 days were used as target cells. They were mixed with dilutions of spleen and lymph node cells obtained from mice at various times after infection with MSV-M. The cell mixtures were incubated for 5 hours, then injected into mice, and tumor inhibiting activity was determined after an observation period of 14 days. Tumor inhibiting capacity was demonstrated with cells harvested from mice 8 days after infection with MSV-M, it was strongest with cells obtained at the stage of peak tumor size and during regression, and was still demonstrable with cells taken at the 86th day after infection. Pretreatment of the lymphoid cells with anti-0-antibodies and complement abolished the tumor inhibiting capacity. This result indicates that immune T cells abrogate the capacity of the ascitic tumor cells to induce tumor development.", "contents": "Tumor inhibiting capacity of spleen and lymph node cells from mice with murine sarcoma virus (MSV-M)-induced tumors. The direct tumor inhibiting capacity of spleen and lymph node cells obtained from mice in different stages of Moloney sarcoma virus (MSV-M)-induced tumor development was studied. MSV-M producing ascitic tumor cells with a tumor dosis50 of about 10(3) cells and a mean latent period--depending on the amount of transplanted cells--of6-12 days were used as target cells. They were mixed with dilutions of spleen and lymph node cells obtained from mice at various times after infection with MSV-M. The cell mixtures were incubated for 5 hours, then injected into mice, and tumor inhibiting activity was determined after an observation period of 14 days. Tumor inhibiting capacity was demonstrated with cells harvested from mice 8 days after infection with MSV-M, it was strongest with cells obtained at the stage of peak tumor size and during regression, and was still demonstrable with cells taken at the 86th day after infection. Pretreatment of the lymphoid cells with anti-0-antibodies and complement abolished the tumor inhibiting capacity. This result indicates that immune T cells abrogate the capacity of the ascitic tumor cells to induce tumor development."} {"id": "PMID:181929", "title": "[New structural components detected in B. pertussis of different serotypes].", "content": "The authors present electron microscopic data on the study of morphological peculiarities of the strains belonging to various serological types. All the strains studied had a structure characteristic of Gram-negative bacteria. Two types intracellular membranes and intracytoplasmic crystal-like structures were revealed in a number of strains (No. 222, No. gZ353, No. 475), irrespective of the serological types. Dynamics of formation of the crystal-like structures in the bacterial cell was described. Marked changes occurred in the cells with the formation of crystal-like structures: cytoplasmic membrane became detached from the cell wall with the resultant contraction of the cytoplasm; large periplastic spaces formed.", "contents": "[New structural components detected in B. pertussis of different serotypes]. The authors present electron microscopic data on the study of morphological peculiarities of the strains belonging to various serological types. All the strains studied had a structure characteristic of Gram-negative bacteria. Two types intracellular membranes and intracytoplasmic crystal-like structures were revealed in a number of strains (No. 222, No. gZ353, No. 475), irrespective of the serological types. Dynamics of formation of the crystal-like structures in the bacterial cell was described. Marked changes occurred in the cells with the formation of crystal-like structures: cytoplasmic membrane became detached from the cell wall with the resultant contraction of the cytoplasm; large periplastic spaces formed."} {"id": "PMID:181931", "title": "Synthesis of penicillin analogs, (--)-methyl 6-epi-6-bromobisnorpenicillanate and (+/-)-methyl 6-epi-bromopenicillanate.", "content": "The [(4-methoxycarbonylthiazolidino)carbonyl-dihalomethyl]phenylmercury compounds 2a,b and 5a,b have been synthesized. When heated in refluxing bromobenzene they form halogenated penicillin analogs. (--)-Methyl 6-epi-6-bromobisnorpenicillinate (3a) and methyl 6-epi-6-bromopenicillinates (6a,b) have been prepared and isolated.", "contents": "Synthesis of penicillin analogs, (--)-methyl 6-epi-6-bromobisnorpenicillanate and (+/-)-methyl 6-epi-bromopenicillanate. The [(4-methoxycarbonylthiazolidino)carbonyl-dihalomethyl]phenylmercury compounds 2a,b and 5a,b have been synthesized. When heated in refluxing bromobenzene they form halogenated penicillin analogs. (--)-Methyl 6-epi-6-bromobisnorpenicillinate (3a) and methyl 6-epi-6-bromopenicillinates (6a,b) have been prepared and isolated."} {"id": "PMID:181927", "title": "[Comparative characteristics of the functional state of the adrenal cortex in the dogs and the fox, Vulpes fulvus].", "content": "Comparison has been made of secretory activity of the adrenals in silver foxes and dogs. Besides, studies were made of the effect of ACTH and angiotensin II on the production of gluco- and mineral corticoids by the adrenals in these animals. It was shown that the spectrum and number of main corticosteroids produced by the adrenals in vitro is identical infoxes and dogs. No difference was found between these animals with respect to the reaction of the adrenals to the addition of ACHT and angiotensin to the incubation medium, although in foxes more significant reaction of glucocorticoid part of the adrenals to ACTH was noted.", "contents": "[Comparative characteristics of the functional state of the adrenal cortex in the dogs and the fox, Vulpes fulvus]. Comparison has been made of secretory activity of the adrenals in silver foxes and dogs. Besides, studies were made of the effect of ACTH and angiotensin II on the production of gluco- and mineral corticoids by the adrenals in these animals. It was shown that the spectrum and number of main corticosteroids produced by the adrenals in vitro is identical infoxes and dogs. No difference was found between these animals with respect to the reaction of the adrenals to the addition of ACHT and angiotensin to the incubation medium, although in foxes more significant reaction of glucocorticoid part of the adrenals to ACTH was noted."} {"id": "PMID:181933", "title": "Radioligand receptor assay of FSH.", "content": "The assay of FSH by a radioligand receptor assay (RLA) using homogenates of rat testicular tissue incubated for 17 h at 21 degrees C has been assessed. Chloramine-T or lactoperoxidase were used for iodination. The assay gave linear dose-response lines between 30 and 2000 ng sheep FSH/tube, and there was usually no major interference by LH. Two batches of labelled FSH, however, gave assays in which LH showed a striking interaction with FSH. When these batches were avoided and FSH and LH were mixed in ratios that differed less than fourfold, the assay was combined successfully, in the same tubes, with an RLA for LH, using LH and FSH labelled with 131I and 125I respectively. The RLA for FSH was not suitable for assay of FSH in rat serum because of apparent non-specific interference. Assay by RLA of rat FSH, in pituitary homogenates or released during incubation in vitro, gave results which were not closely correlated with those of either conventional bioassay or radioimmunoassay.", "contents": "Radioligand receptor assay of FSH. The assay of FSH by a radioligand receptor assay (RLA) using homogenates of rat testicular tissue incubated for 17 h at 21 degrees C has been assessed. Chloramine-T or lactoperoxidase were used for iodination. The assay gave linear dose-response lines between 30 and 2000 ng sheep FSH/tube, and there was usually no major interference by LH. Two batches of labelled FSH, however, gave assays in which LH showed a striking interaction with FSH. When these batches were avoided and FSH and LH were mixed in ratios that differed less than fourfold, the assay was combined successfully, in the same tubes, with an RLA for LH, using LH and FSH labelled with 131I and 125I respectively. The RLA for FSH was not suitable for assay of FSH in rat serum because of apparent non-specific interference. Assay by RLA of rat FSH, in pituitary homogenates or released during incubation in vitro, gave results which were not closely correlated with those of either conventional bioassay or radioimmunoassay."} {"id": "PMID:181934", "title": "Augmented secretion of TSH in response to TRH after pre-treatment with dexamethasone for six days in rats.", "content": "Serum TSH and corticosterone concentrations were measured in rats given TRH or exposed to short-term cold, as well as in intact rats, after pre-treatment with dexamethasone for six days at two different dose levels (25 and 250 mug/100 g body weight). Both doses increased the secretion of TSH in response to TRH whereas cold-induced TSH secretion was not modified by pre-treatment with dexamethasone. In intact rats serum TSH levels did not differ significantly from controls. In all experiments the steroid blocked ACTH secretion. It was also found that administration of TRH produced a rise in serum corticosterone concentrations. Our results support the view that dexamethasone given for six days facilitates TRH stimulation of the pituitary whilst simultaneously inhibiting the secretion of TRH in response to cold.", "contents": "Augmented secretion of TSH in response to TRH after pre-treatment with dexamethasone for six days in rats. Serum TSH and corticosterone concentrations were measured in rats given TRH or exposed to short-term cold, as well as in intact rats, after pre-treatment with dexamethasone for six days at two different dose levels (25 and 250 mug/100 g body weight). Both doses increased the secretion of TSH in response to TRH whereas cold-induced TSH secretion was not modified by pre-treatment with dexamethasone. In intact rats serum TSH levels did not differ significantly from controls. In all experiments the steroid blocked ACTH secretion. It was also found that administration of TRH produced a rise in serum corticosterone concentrations. Our results support the view that dexamethasone given for six days facilitates TRH stimulation of the pituitary whilst simultaneously inhibiting the secretion of TRH in response to cold."} {"id": "PMID:181935", "title": "Breast cancer in the Forbes-Albright syndrome.", "content": "A 33 year old woman with persistent galactorrhoea developed breast cancer six years after pituitary radiation for a pituitary adenoma (Forbes-Albright syndrome). The possible role of prolactin in human mammary cacinoma is discussed.", "contents": "Breast cancer in the Forbes-Albright syndrome. A 33 year old woman with persistent galactorrhoea developed breast cancer six years after pituitary radiation for a pituitary adenoma (Forbes-Albright syndrome). The possible role of prolactin in human mammary cacinoma is discussed."} {"id": "PMID:181936", "title": "Regulation of the activities of the enzymes involved in the metabolism of steroid hormones in rat liver: the effect of administration of anterior hypophyseal hormones and gonadotrophin preparations to hypophysectomized rats.", "content": "A crude human hypophyseal extract (HE), as well as human growth hormone (GH), ovine prolactin (PRL) and commercial preparations of ACTH, TSH, pregnant mare's serum gonadotrophins (PMS) and chorionic gonadotrophin (CG) were tested for their ability to induce the activities of cytoplasmic 17 beta-hydroxysteroid dehydrogenase and microsomal delta 4-5alpha-hydrogenase and to repress the activities of microsomal 3alpha- and 3beta-hydroxysteroid dehydrogenases in the liver of hypophysectomized rats. The activity of 17beta-hydroxysteroid dehydrogenase was not affected by any of the administered hormones. For the other enzymes, only PRL was effective in causing changes in the activities; the repressive effect on 3alpha-hydroxysteroid dehydrogenase activity was highly significant (P less than 0.001). These results indicate that PRL is involved in the regulation of at least some of the enzyme activities of hepatic steroid hormone metabolism.", "contents": "Regulation of the activities of the enzymes involved in the metabolism of steroid hormones in rat liver: the effect of administration of anterior hypophyseal hormones and gonadotrophin preparations to hypophysectomized rats. A crude human hypophyseal extract (HE), as well as human growth hormone (GH), ovine prolactin (PRL) and commercial preparations of ACTH, TSH, pregnant mare's serum gonadotrophins (PMS) and chorionic gonadotrophin (CG) were tested for their ability to induce the activities of cytoplasmic 17 beta-hydroxysteroid dehydrogenase and microsomal delta 4-5alpha-hydrogenase and to repress the activities of microsomal 3alpha- and 3beta-hydroxysteroid dehydrogenases in the liver of hypophysectomized rats. The activity of 17beta-hydroxysteroid dehydrogenase was not affected by any of the administered hormones. For the other enzymes, only PRL was effective in causing changes in the activities; the repressive effect on 3alpha-hydroxysteroid dehydrogenase activity was highly significant (P less than 0.001). These results indicate that PRL is involved in the regulation of at least some of the enzyme activities of hepatic steroid hormone metabolism."} {"id": "PMID:181937", "title": "Inhibition and facilitation of feedback influences of dexamethasone on adrenocortical responses to ether stress in rats with hypothalamic deafferentations and brain lesions.", "content": "In order to elucidate the mechanisms and the sites of action of the negative feedback of corticoids in the regulation of ACTH secretion, the effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact rats and in 11 experimental groups. These included animals with partial anterior, anterolateral, posterolateral, posterior and small posterior deafferentations as well as bilateral lesions in the medial forebrain bundle (MFB), fasciculus longitudinalis dorsalis (FLD), medial and lateral midbrain reticular formation (MRF) and in the ventrolateral pons. In rats with posterior hypothalamic deafferentation the degree of the inhibitory effect of dexamethasone was much smaller than that in intact animals. In animals with lesions in the FLD and MRF, dexamethasone also produced a reduction in the suppression of the response, though the difference was not significant. Bilateral lesions in the MFB and MP have on the other hand very significantly enhanced the effect of the negative feedback of dexamethasone when compared to intact rats. These data would indicate that hypothalamic deafferentations and brain lesions may change the sensitivity of the hypothalamus for the feedback control of corticoids and that there exist two antagonistic systems, an inhibitory and a facilitatory, in the brain which mediate this effect.", "contents": "Inhibition and facilitation of feedback influences of dexamethasone on adrenocortical responses to ether stress in rats with hypothalamic deafferentations and brain lesions. In order to elucidate the mechanisms and the sites of action of the negative feedback of corticoids in the regulation of ACTH secretion, the effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact rats and in 11 experimental groups. These included animals with partial anterior, anterolateral, posterolateral, posterior and small posterior deafferentations as well as bilateral lesions in the medial forebrain bundle (MFB), fasciculus longitudinalis dorsalis (FLD), medial and lateral midbrain reticular formation (MRF) and in the ventrolateral pons. In rats with posterior hypothalamic deafferentation the degree of the inhibitory effect of dexamethasone was much smaller than that in intact animals. In animals with lesions in the FLD and MRF, dexamethasone also produced a reduction in the suppression of the response, though the difference was not significant. Bilateral lesions in the MFB and MP have on the other hand very significantly enhanced the effect of the negative feedback of dexamethasone when compared to intact rats. These data would indicate that hypothalamic deafferentations and brain lesions may change the sensitivity of the hypothalamus for the feedback control of corticoids and that there exist two antagonistic systems, an inhibitory and a facilitatory, in the brain which mediate this effect."} {"id": "PMID:181932", "title": "Serum and pancreatic immunoreactive insulin (IRI) and proinsulin-like component (PLC), serum IRI and PLC response to different stimuli in normal subjects and organic hyperinsulinism.", "content": "The serum levels of total immunoreactive insulin (IRI) and proinsulin-like component (PLC) in the fasting state and following the administration of insulin secretagogues in 5 patients with organic hyperinsulinism and age and sex matched normal subjects are reported. Diagnosis of organic hyperinsulinism could be established in all instances on the basis of the inappropriately high total serum IRI levels for the corresponding blood glucose values; such an abnormal relationship was not seen in normal subjects, and was further enhanced by insulin secretagogues. Unrestrained insulin secretion in organic hyperinsulinism was enhanced following the administration of glucose, tolbutamide, glucagon or amino acids; the last 2 stimuli are known to be ineffective in causing insulin secretion in the presence of hypoglycemia in normal subjects. Four patints had insulinomas and one probably had islet cell hyperplasia or abnormal function of islet cells. Chromatography of serum IRI to quantitate PLC is a useful adjunct to the diagnosis of organic hyperinsulinism as in the fasting state the proportion of PLC is always elevated, above the normal range of 5-22%. Following the administration of insulin secretagogues there was pronounced increase in total serum IRI in organic hyperinsulinism but the proportion of PLC generally decreased, suggesting thereby that mojor increase in IRI was due to release of stored granular IRI which is known to have a low proportion of PLC.", "contents": "Serum and pancreatic immunoreactive insulin (IRI) and proinsulin-like component (PLC), serum IRI and PLC response to different stimuli in normal subjects and organic hyperinsulinism. The serum levels of total immunoreactive insulin (IRI) and proinsulin-like component (PLC) in the fasting state and following the administration of insulin secretagogues in 5 patients with organic hyperinsulinism and age and sex matched normal subjects are reported. Diagnosis of organic hyperinsulinism could be established in all instances on the basis of the inappropriately high total serum IRI levels for the corresponding blood glucose values; such an abnormal relationship was not seen in normal subjects, and was further enhanced by insulin secretagogues. Unrestrained insulin secretion in organic hyperinsulinism was enhanced following the administration of glucose, tolbutamide, glucagon or amino acids; the last 2 stimuli are known to be ineffective in causing insulin secretion in the presence of hypoglycemia in normal subjects. Four patints had insulinomas and one probably had islet cell hyperplasia or abnormal function of islet cells. Chromatography of serum IRI to quantitate PLC is a useful adjunct to the diagnosis of organic hyperinsulinism as in the fasting state the proportion of PLC is always elevated, above the normal range of 5-22%. Following the administration of insulin secretagogues there was pronounced increase in total serum IRI in organic hyperinsulinism but the proportion of PLC generally decreased, suggesting thereby that mojor increase in IRI was due to release of stored granular IRI which is known to have a low proportion of PLC."} {"id": "PMID:181938", "title": "Oocyte maturation and glycolysis in isolated pre-ovulatory follicles of PMS-injected immature rats.", "content": "Graafian follicles were isolated by microdissection from the ovaries of PMS-injected immature rats killed at specific times on the day before ovulation. They were incubated in Krebs bicarbonate buffer containing 5 mM glucose and 1% bovine serum albumin. The oocytes were recovered after incubation and examined by Nomarski interference contrast microscopy. The amount of lactate and glucose in the incubation medium was analysed enzymatically. Oocytes recovered from follicles extirpated in the morning, i.e. before the endogenous LH surge, and incubated for 2-10 h were in the dictyate stage, while addition of LH or FSH to the medium resulted in oocyte maturation as revealed by germinal vesicle breakdown (GVB) and polar body formation. The time-course of GVB in vitro was similar to that seen in vivo after exogenous LH. Both gonadotrophins markedly enhanced lactate accumulation in the medium and, as studied for LH, glucose uptake by the follicles. The effects of LH but not those of FSH, on GVB and lactate formation were prevented by the presence of an antiserum against the beta-subunit of LH. The gonadotrophic effects on GVB could be mimicked by the addition of prostaglandin E2 to the medium. When the follicles were extirpated in the late afternoon, i.e. after the LH surge, and incubated in hormone-free medium for 4 h the oocytes showed GVB in a progressively increasing proportion depending on the time of follicle extirpation. Lactate formation by this group of follicles was markedly enhanced compared to that of \"morning\" follicles, but it could be even more stimulated by in vitro exposure to LH. A preliminary series of experiments on the effect of phosphodiesterase inhibitors showed that theophylline and isobutylmethylxanthine at certain concentrations completely blocked the LH effect on GVB, whereas a newly developed compound, ICI 63.197, in itself induced GVB.", "contents": "Oocyte maturation and glycolysis in isolated pre-ovulatory follicles of PMS-injected immature rats. Graafian follicles were isolated by microdissection from the ovaries of PMS-injected immature rats killed at specific times on the day before ovulation. They were incubated in Krebs bicarbonate buffer containing 5 mM glucose and 1% bovine serum albumin. The oocytes were recovered after incubation and examined by Nomarski interference contrast microscopy. The amount of lactate and glucose in the incubation medium was analysed enzymatically. Oocytes recovered from follicles extirpated in the morning, i.e. before the endogenous LH surge, and incubated for 2-10 h were in the dictyate stage, while addition of LH or FSH to the medium resulted in oocyte maturation as revealed by germinal vesicle breakdown (GVB) and polar body formation. The time-course of GVB in vitro was similar to that seen in vivo after exogenous LH. Both gonadotrophins markedly enhanced lactate accumulation in the medium and, as studied for LH, glucose uptake by the follicles. The effects of LH but not those of FSH, on GVB and lactate formation were prevented by the presence of an antiserum against the beta-subunit of LH. The gonadotrophic effects on GVB could be mimicked by the addition of prostaglandin E2 to the medium. When the follicles were extirpated in the late afternoon, i.e. after the LH surge, and incubated in hormone-free medium for 4 h the oocytes showed GVB in a progressively increasing proportion depending on the time of follicle extirpation. Lactate formation by this group of follicles was markedly enhanced compared to that of \"morning\" follicles, but it could be even more stimulated by in vitro exposure to LH. A preliminary series of experiments on the effect of phosphodiesterase inhibitors showed that theophylline and isobutylmethylxanthine at certain concentrations completely blocked the LH effect on GVB, whereas a newly developed compound, ICI 63.197, in itself induced GVB."} {"id": "PMID:181939", "title": "Intramitochondrial crystalline inclusions in the liver of a patient with hyperthyroidism.", "content": "The case of a female patient with hyperthyroidism and slightly impaired liver function is described. Histological examination of liver biopsy did not reveal any pathological findings. Electron microscopic examination revealed crystalline inclusions in a great number of the mitochondria of the liver cells, as well as increased size of the mitochondira. Similar findings were obtained upon examination of a liver biopsy performed six months after start of treatment for hyperthyroidism. Examination of the skin, muscle and white blood cells did not show the presence of such inclusions in the mitochondria. The significance of these findings in the liver cells is discussed.", "contents": "Intramitochondrial crystalline inclusions in the liver of a patient with hyperthyroidism. The case of a female patient with hyperthyroidism and slightly impaired liver function is described. Histological examination of liver biopsy did not reveal any pathological findings. Electron microscopic examination revealed crystalline inclusions in a great number of the mitochondria of the liver cells, as well as increased size of the mitochondira. Similar findings were obtained upon examination of a liver biopsy performed six months after start of treatment for hyperthyroidism. Examination of the skin, muscle and white blood cells did not show the presence of such inclusions in the mitochondria. The significance of these findings in the liver cells is discussed."} {"id": "PMID:181940", "title": "Primary liver carcinoma -- clinical picture and diagnostic possibilities. A review of seventy-five cases.", "content": "A study was performed on a group of 75 patients with primary liver carcinoma (PLC) treated at the 1st Medical Department in Prague during past 24 years. The average age of patients when they died was 59.9 years. 86.7 per cent of the patients were men; in 88.0 per cent of cases PLC was associated with liver cirrhosis. It was found that the frequency of PLC incidence is increasing. Case histories, subjective complaints and laboratory findings were analyzed in these patients. The diagnostic contribution of some examination methods was evaluated (laparoscopy with the aimed liver biopsy in 50% of the cases, isotopic methods in 34.6% of cases, roentgenologic methods in 36.0% of cases, detection of alpha-1 fetoprotein in serum in 55.5% of cases). The analysis of causes of death was also performed. Histologic classification proved the hepatocellular carcinoma in 94.6 per cent of patients, the cholangiocellular carcinoma was found only in 4 patients. The agreement of clinical diagnoses with the pathologic-anatomical diagnosis was found in 70.6% of cases.", "contents": "Primary liver carcinoma -- clinical picture and diagnostic possibilities. A review of seventy-five cases. A study was performed on a group of 75 patients with primary liver carcinoma (PLC) treated at the 1st Medical Department in Prague during past 24 years. The average age of patients when they died was 59.9 years. 86.7 per cent of the patients were men; in 88.0 per cent of cases PLC was associated with liver cirrhosis. It was found that the frequency of PLC incidence is increasing. Case histories, subjective complaints and laboratory findings were analyzed in these patients. The diagnostic contribution of some examination methods was evaluated (laparoscopy with the aimed liver biopsy in 50% of the cases, isotopic methods in 34.6% of cases, roentgenologic methods in 36.0% of cases, detection of alpha-1 fetoprotein in serum in 55.5% of cases). The analysis of causes of death was also performed. Histologic classification proved the hepatocellular carcinoma in 94.6 per cent of patients, the cholangiocellular carcinoma was found only in 4 patients. The agreement of clinical diagnoses with the pathologic-anatomical diagnosis was found in 70.6% of cases."} {"id": "PMID:181941", "title": "Perivascular lymphocytic cuffing in astrocytomas.", "content": "A series of cases of astrocytoma of differing cell composition and degree of malignancy was examined for the presence of reactive perivascular cuffing. Only surgical biopsy material was used. A correlation was made between perivascular lymphocyte cuffing and the presence of neoplastic astrocytes of the gemistocytic type.", "contents": "Perivascular lymphocytic cuffing in astrocytomas. A series of cases of astrocytoma of differing cell composition and degree of malignancy was examined for the presence of reactive perivascular cuffing. Only surgical biopsy material was used. A correlation was made between perivascular lymphocyte cuffing and the presence of neoplastic astrocytes of the gemistocytic type."} {"id": "PMID:181943", "title": "Production of human lens capsule illustrated by a case of chronic lenticular chalcosis.", "content": "The osmiophilic capsular inclusion bodies in a case of accidental lenticular chalcosis have been used as an in vivo indicator of capsular production. Copper stimulation and hence inclusion impregnation lasted 5 years and was stopped 2 years before removal of the lens by extraction of a foreign body. The amount of capsule produced in the two year period varied at different locations but it greatly exceeded the previously measured quantities. A capsular turnover is postulated with a capsular production by the epithelial cells and a surface resorption process. The production rate is considered to be relatively high in childhood and gradually subsides with increasing age.", "contents": "Production of human lens capsule illustrated by a case of chronic lenticular chalcosis. The osmiophilic capsular inclusion bodies in a case of accidental lenticular chalcosis have been used as an in vivo indicator of capsular production. Copper stimulation and hence inclusion impregnation lasted 5 years and was stopped 2 years before removal of the lens by extraction of a foreign body. The amount of capsule produced in the two year period varied at different locations but it greatly exceeded the previously measured quantities. A capsular turnover is postulated with a capsular production by the epithelial cells and a surface resorption process. The production rate is considered to be relatively high in childhood and gradually subsides with increasing age."} {"id": "PMID:181944", "title": "Bacteria in hip surgery. A study of routine aerobic and anaerobic cultivation from skin and closed suction wound drains.", "content": "One hundred and seven patients with closed suction wound drains after hip surgery were investigated with regard to bacteria in the drain. In one-third of the cases bacterial contamination of the wound was found. In more than half the total number of cases the bacteria in the wound were not identical with those found on the skin, either pre- or post-operatively. Anaerobe bacteria occurred only in one case. Penicillin administration considerably reduced the frequency of positive cultures. These findings support the prophylactic use of antibiotics in the prevention of late infections in endoprosthesis operations even when the early infection rate is satisfactorily low.", "contents": "Bacteria in hip surgery. A study of routine aerobic and anaerobic cultivation from skin and closed suction wound drains. One hundred and seven patients with closed suction wound drains after hip surgery were investigated with regard to bacteria in the drain. In one-third of the cases bacterial contamination of the wound was found. In more than half the total number of cases the bacteria in the wound were not identical with those found on the skin, either pre- or post-operatively. Anaerobe bacteria occurred only in one case. Penicillin administration considerably reduced the frequency of positive cultures. These findings support the prophylactic use of antibiotics in the prevention of late infections in endoprosthesis operations even when the early infection rate is satisfactorily low."} {"id": "PMID:181951", "title": "Elimination of water-soluble contrast media from the subarachnoid space. Investigation with computer tomography.", "content": "Contrast media injected into the subarachnoid space may be eliminated in two different ways, by diffusion through the meningeal membranes or by transport through these CSF pathways. The latter mode of transport may be examined using computer assisted tomography of the head. Diffusion predominants with contrast media of low molecular weight, such as methiodal sodium. The transport through the CSF cihculation increases when contrast media of high molecular weight such as meglumine iocarmate and metrizamide are used.", "contents": "Elimination of water-soluble contrast media from the subarachnoid space. Investigation with computer tomography. Contrast media injected into the subarachnoid space may be eliminated in two different ways, by diffusion through the meningeal membranes or by transport through these CSF pathways. The latter mode of transport may be examined using computer assisted tomography of the head. Diffusion predominants with contrast media of low molecular weight, such as methiodal sodium. The transport through the CSF cihculation increases when contrast media of high molecular weight such as meglumine iocarmate and metrizamide are used."} {"id": "PMID:181952", "title": "A variant of Poland syndrome: report of case.", "content": "A variant case of Poland syndrome is reported, with the patient presenting major unilateral anomalies in the sternocostal head of the left pectoralis major muscle and a shorter left arm and hand. No pre-natal history of attempted abortion or using toxic or teratogenic drugs could be elicited. The variability of the upper extremity anomalies and the frequency of major ipsilateral defects of the skeletal and genite-urinary systems, the associated diseases, and the diagnosis and management of these patients are briefly discussed.", "contents": "A variant of Poland syndrome: report of case. A variant case of Poland syndrome is reported, with the patient presenting major unilateral anomalies in the sternocostal head of the left pectoralis major muscle and a shorter left arm and hand. No pre-natal history of attempted abortion or using toxic or teratogenic drugs could be elicited. The variability of the upper extremity anomalies and the frequency of major ipsilateral defects of the skeletal and genite-urinary systems, the associated diseases, and the diagnosis and management of these patients are briefly discussed."} {"id": "PMID:181954", "title": "[Incidence and clinical features of pituitary tumours in cases of central Cushing's syndrome (author's transl)].", "content": "Approximately 10% of all patients with untreated central Cushing's syndromes have clinically verifiable tumours of the pituitary. After bilateral adrenalectomy 10 to 20% of patients with apparently normal pre-operative pituitary glands develop clinically and roentgenologically demonstrable pituitary tumours, of the so called Nelson type. These are usually very active chromophobe adenomas which are dangerous because they expand rapidly. They secretee considerable amounts of ACTH and MSH. A typical case is described.", "contents": "[Incidence and clinical features of pituitary tumours in cases of central Cushing's syndrome (author's transl)]. Approximately 10% of all patients with untreated central Cushing's syndromes have clinically verifiable tumours of the pituitary. After bilateral adrenalectomy 10 to 20% of patients with apparently normal pre-operative pituitary glands develop clinically and roentgenologically demonstrable pituitary tumours, of the so called Nelson type. These are usually very active chromophobe adenomas which are dangerous because they expand rapidly. They secretee considerable amounts of ACTH and MSH. A typical case is described."} {"id": "PMID:181955", "title": "[Postoperative radiological control in space occupying lesions of the sellar region (author's transl)].", "content": "Different methods of postoperative radiological examination of space occupying lesions of the sellar region are discussed with regard to early diagnosis of recurrences. The important role of regular controls by lateral radiographs of the skull is stressed in this follow up survey of 164 cases over a period of 23 years. Comparisons of radiographs over a period showed in 80% of our cases whether there was a tumour recurrence or not. Radiological changes in the area of the sella can be demonstrated more clearly by the use of magnified lateral radiographs and a centimetre rule. With regard to frequency and time of recurrence, 40% of first recurrences were found after 5 years, so periodic radiographic follow up X-ray examinations should be carried out six monthly intially, and later at twelve month intervals. Examples are demonstrated. Intraoperative marking of the diaphragm and dorsum sellae with gold foil for later control radiography is evaluated. Today, space occupying lesions, including intrasellar pituitary tumours, can be clearly demonstrated with the CT scan after i.v. injection of contrast medium to intensity the shadow of the tumour tissue.", "contents": "[Postoperative radiological control in space occupying lesions of the sellar region (author's transl)]. Different methods of postoperative radiological examination of space occupying lesions of the sellar region are discussed with regard to early diagnosis of recurrences. The important role of regular controls by lateral radiographs of the skull is stressed in this follow up survey of 164 cases over a period of 23 years. Comparisons of radiographs over a period showed in 80% of our cases whether there was a tumour recurrence or not. Radiological changes in the area of the sella can be demonstrated more clearly by the use of magnified lateral radiographs and a centimetre rule. With regard to frequency and time of recurrence, 40% of first recurrences were found after 5 years, so periodic radiographic follow up X-ray examinations should be carried out six monthly intially, and later at twelve month intervals. Examples are demonstrated. Intraoperative marking of the diaphragm and dorsum sellae with gold foil for later control radiography is evaluated. Today, space occupying lesions, including intrasellar pituitary tumours, can be clearly demonstrated with the CT scan after i.v. injection of contrast medium to intensity the shadow of the tumour tissue."} {"id": "PMID:181962", "title": "Phospholipid-induced modifications in the brain of animals fed with cholesterol-supplemented diet.", "content": "1) Cholesterol - enriched diet induces changes in the phospholipid fatty acids of particulate fractions and modifications in the membrane-bound enzyme: 2) BC-PL (100 mg/kg i.p., as shown in rabbits) prevent cholesterol-induced modifications at brain level: 3)BC-PL (100 mg/kg i.v., as shown in mice) have a recovery effect on the cholesterol-induced modification at brain level; 4) It is suggested that some atherosclerotic lesions are analogous to those reproduced by anoxia; 5) It is suggested that the effect of BC-PL is a direct action at the level of the brain cellular membranes.", "contents": "Phospholipid-induced modifications in the brain of animals fed with cholesterol-supplemented diet. 1) Cholesterol - enriched diet induces changes in the phospholipid fatty acids of particulate fractions and modifications in the membrane-bound enzyme: 2) BC-PL (100 mg/kg i.p., as shown in rabbits) prevent cholesterol-induced modifications at brain level: 3)BC-PL (100 mg/kg i.v., as shown in mice) have a recovery effect on the cholesterol-induced modification at brain level; 4) It is suggested that some atherosclerotic lesions are analogous to those reproduced by anoxia; 5) It is suggested that the effect of BC-PL is a direct action at the level of the brain cellular membranes."} {"id": "PMID:181966", "title": "The regulatory role of steroid hormones on the PGF/PGE ratio in target tissues.", "content": "Estrogen has been found to regulate cyclic nucleotide and prostaglandin levels in the rat uterus. This action of estrogen is associated with a simultaneous rise in cyclic GMP and PFG levels. Alterations in PG levels are either independent of or secondary to the formation of cyclic GMP. The mechanism by which estrogen induces the rise in uterine PGFs, although not precisely defined, is associated with alterations of the enzymes rather than of the substrates involved with prostglandin synthesis.", "contents": "The regulatory role of steroid hormones on the PGF/PGE ratio in target tissues. Estrogen has been found to regulate cyclic nucleotide and prostaglandin levels in the rat uterus. This action of estrogen is associated with a simultaneous rise in cyclic GMP and PFG levels. Alterations in PG levels are either independent of or secondary to the formation of cyclic GMP. The mechanism by which estrogen induces the rise in uterine PGFs, although not precisely defined, is associated with alterations of the enzymes rather than of the substrates involved with prostglandin synthesis."} {"id": "PMID:181967", "title": "Mechanisms by which leukocytes emigrate and induce tissue destruction.", "content": "Chronic inflammatory reactions are characterized by emigration of leukocytes to chemotactic stimuli and the subsequent release of intracellular enzymes which propogate the inflammatory reaction and cause tissue injury. The adoptive transfer of isologous 51Cr labeled leukocytes was used as a model to dissect the cellular mechanisms involved in cell accumulation to the site of immune complex or complement mediated inflammatory reactions. An intact microtubular system was necessary only for neutrophil emigration whereas cell membrane integrity was necessary for mononuclear cell but not neutrophil accumulation in vivo. The accumulation of both cell types was inhibited following phagocytosis or in the presence of corticosteroids. Release of protein polysaccharide degrading neutral protease activity from leukocytes in the presence of immune complexes was dependent upon intact microtubular activity and cell membrane integrity since agents affecting these systems inhibited enzyme release. Conversely collagenase activity released from leukocytes under the same conditions was not inhibited by these agents. Evidence will be presented indicating that the emigration of specific cell types and the release of selected enzyme systems are controlled by separate and distinct mechanistic pathways.", "contents": "Mechanisms by which leukocytes emigrate and induce tissue destruction. Chronic inflammatory reactions are characterized by emigration of leukocytes to chemotactic stimuli and the subsequent release of intracellular enzymes which propogate the inflammatory reaction and cause tissue injury. The adoptive transfer of isologous 51Cr labeled leukocytes was used as a model to dissect the cellular mechanisms involved in cell accumulation to the site of immune complex or complement mediated inflammatory reactions. An intact microtubular system was necessary only for neutrophil emigration whereas cell membrane integrity was necessary for mononuclear cell but not neutrophil accumulation in vivo. The accumulation of both cell types was inhibited following phagocytosis or in the presence of corticosteroids. Release of protein polysaccharide degrading neutral protease activity from leukocytes in the presence of immune complexes was dependent upon intact microtubular activity and cell membrane integrity since agents affecting these systems inhibited enzyme release. Conversely collagenase activity released from leukocytes under the same conditions was not inhibited by these agents. Evidence will be presented indicating that the emigration of specific cell types and the release of selected enzyme systems are controlled by separate and distinct mechanistic pathways."} {"id": "PMID:181968", "title": "Dissociation of phagocytosis, metabolic stimulation and lysosomal enzyme release in human leukocytes.", "content": "In this paper studies are reported concerning the relationship between particle binding to the plasma membrane of human polymorphonuclear leukocytes (PMN's), phagocytosis, generation of oxidative metabolites, and the release of lysosomal enzymes by these cells. Superoxide (O2-) generation by, and lysosomal enzyme release from, normal PMN's and cytochalasin B-treated cells were measured. We have found that neither phagocytosis nor lysosomal degranulation are prerequisites for enhanced O2- generation. Cytochalasin B-treated PMN's, incapable of ingesting particles but still able to bind particles to membrane receptors, generated enhanced amounts of O2- when treated with serum-treated zymosan (STZ), a C3b receptor stimulus, or with aggregated IgG (agg IgG), an Fc receptor stimulus. Moreover, the soluble stimulators complement component C5a, phorbol myristate acetate (PMA), and calcium ions in the presence of the ionophore A23187, also increased the O2- production of these cells. In all cases a time and dose-dependent stimulation was found of both the O2- generation and the lysosomal enzyme release, but there was no correlation between ability of any stimulus to provoke enzyme release and its ability to stimulate O2- generation. When PMN's were preincubated with 5 X 10(-4) M hydrocortisone-Na-succinate, lysosomal enzyme exocytosis with the immune reactants was inhibited 16-35%. Hydrocortisone also inhibited O2- generation, except when STZ was used as the stimulus. Thus, in the case of stimulation of functional processes of PMN's via the C3b receptor, hydrocortisone inhibits membrane fusion without interfering with one of the early biochemical events (O2-production).", "contents": "Dissociation of phagocytosis, metabolic stimulation and lysosomal enzyme release in human leukocytes. In this paper studies are reported concerning the relationship between particle binding to the plasma membrane of human polymorphonuclear leukocytes (PMN's), phagocytosis, generation of oxidative metabolites, and the release of lysosomal enzymes by these cells. Superoxide (O2-) generation by, and lysosomal enzyme release from, normal PMN's and cytochalasin B-treated cells were measured. We have found that neither phagocytosis nor lysosomal degranulation are prerequisites for enhanced O2- generation. Cytochalasin B-treated PMN's, incapable of ingesting particles but still able to bind particles to membrane receptors, generated enhanced amounts of O2- when treated with serum-treated zymosan (STZ), a C3b receptor stimulus, or with aggregated IgG (agg IgG), an Fc receptor stimulus. Moreover, the soluble stimulators complement component C5a, phorbol myristate acetate (PMA), and calcium ions in the presence of the ionophore A23187, also increased the O2- production of these cells. In all cases a time and dose-dependent stimulation was found of both the O2- generation and the lysosomal enzyme release, but there was no correlation between ability of any stimulus to provoke enzyme release and its ability to stimulate O2- generation. When PMN's were preincubated with 5 X 10(-4) M hydrocortisone-Na-succinate, lysosomal enzyme exocytosis with the immune reactants was inhibited 16-35%. Hydrocortisone also inhibited O2- generation, except when STZ was used as the stimulus. Thus, in the case of stimulation of functional processes of PMN's via the C3b receptor, hydrocortisone inhibits membrane fusion without interfering with one of the early biochemical events (O2-production)."} {"id": "PMID:181969", "title": "Collagen in granulation tissues.", "content": "Collagen is abundantly synthesized in granulation tissues and reaches a concentration higher than in normal neighbouring tissues. Such newly formed collagen is characterized by an abnormally low solubility and an easy degradation by collagenases and collagenolytic cathepsins. The activities of these two types of enzymes are high (especially collagenases) in tissues of acute inflammations when the granuloma is resorbing. These activities are lower in sub-acute inflammation and the collagen content of the persistent granuloma remains high. The collagen synthesized in granulation tissues is cross linked by hydroxylysino-5-keto-norleucine, the stable cross-link of collagen in embryonic skin. It is progressively replaced by the two aldimine cross links of normal adult skin when the granuloma is resorbed (acute inflammations induced in rats; human normal scars). The cross link of embryonic skin, on the contrary, is permanently present in collagen of tissues of subacute, chronic inflammations (sponge implants in rats, human hypertrophic scars and keloids. Studies of the structure of alpha-chains revealed that type III collagen (embryonic collagen) is present in granulation tissues.", "contents": "Collagen in granulation tissues. Collagen is abundantly synthesized in granulation tissues and reaches a concentration higher than in normal neighbouring tissues. Such newly formed collagen is characterized by an abnormally low solubility and an easy degradation by collagenases and collagenolytic cathepsins. The activities of these two types of enzymes are high (especially collagenases) in tissues of acute inflammations when the granuloma is resorbing. These activities are lower in sub-acute inflammation and the collagen content of the persistent granuloma remains high. The collagen synthesized in granulation tissues is cross linked by hydroxylysino-5-keto-norleucine, the stable cross-link of collagen in embryonic skin. It is progressively replaced by the two aldimine cross links of normal adult skin when the granuloma is resorbed (acute inflammations induced in rats; human normal scars). The cross link of embryonic skin, on the contrary, is permanently present in collagen of tissues of subacute, chronic inflammations (sponge implants in rats, human hypertrophic scars and keloids. Studies of the structure of alpha-chains revealed that type III collagen (embryonic collagen) is present in granulation tissues."} {"id": "PMID:181970", "title": "Anti-inflammatory models in animals.", "content": "The pleural cavity of rats and guinea-pigs has been utilized to study the inflammatory response to immediate hypersensitivity, delayed hypersensitivity, calcium pyrophosphate and carrageenan. The mediators will be described and their possible interaction with cyclic AMP. Finally the effect of some anti-inflammatory agents on these models will be discussed.", "contents": "Anti-inflammatory models in animals. The pleural cavity of rats and guinea-pigs has been utilized to study the inflammatory response to immediate hypersensitivity, delayed hypersensitivity, calcium pyrophosphate and carrageenan. The mediators will be described and their possible interaction with cyclic AMP. Finally the effect of some anti-inflammatory agents on these models will be discussed."} {"id": "PMID:181971", "title": "The macrophage as a secretory cell in chronic inflammation.", "content": "Although it is clear that macrophages are always present at sites of chronic inflammation their contribution to the evolution of these lesions is not well understood. In vitro studies have shown that macrophages secrete a variety of products on exposure to different stimuli. These include hydrolytic enzymes, active at acid or neutral pH, with known capacity for degrading tissue constituents. Lysosomal acid hydrolases are released from viable cells over a prolonged period of time by various agents known to cause, or are associated with, chronic inflammation. These agents may be nonimmunogenic substances, such as carrageenan and asbestos, which interact directly with macrophages or alternatively the products of immune reactions involving either B or T lymphocytes. These lymphocyte products include immune complexes of certain composition and the secreted products of T lymphocytes stimulated by nonspecific mitogens or specific antigens. In marked contrast biologically inactive substances such as latex particles or digestible substrates such as erythrocytes do not induce the selective release of acid hydrolases from macrophages. It is clear that alghough macrophages secrete abundant amounts of neutral proteinases under certain conditions this release does not occur necessarily during the release of acid hydrolases induced by inflammatory agents. The role played by acid and neutral hydrolases secreted by macrophages during the various stages of chronic inflammatory responses remains to be clarified.", "contents": "The macrophage as a secretory cell in chronic inflammation. Although it is clear that macrophages are always present at sites of chronic inflammation their contribution to the evolution of these lesions is not well understood. In vitro studies have shown that macrophages secrete a variety of products on exposure to different stimuli. These include hydrolytic enzymes, active at acid or neutral pH, with known capacity for degrading tissue constituents. Lysosomal acid hydrolases are released from viable cells over a prolonged period of time by various agents known to cause, or are associated with, chronic inflammation. These agents may be nonimmunogenic substances, such as carrageenan and asbestos, which interact directly with macrophages or alternatively the products of immune reactions involving either B or T lymphocytes. These lymphocyte products include immune complexes of certain composition and the secreted products of T lymphocytes stimulated by nonspecific mitogens or specific antigens. In marked contrast biologically inactive substances such as latex particles or digestible substrates such as erythrocytes do not induce the selective release of acid hydrolases from macrophages. It is clear that alghough macrophages secrete abundant amounts of neutral proteinases under certain conditions this release does not occur necessarily during the release of acid hydrolases induced by inflammatory agents. The role played by acid and neutral hydrolases secreted by macrophages during the various stages of chronic inflammatory responses remains to be clarified."} {"id": "PMID:181972", "title": "Adjuvant disease induced by mycobacteria, determinants of arthritogenicity.", "content": "Genetic, endocrine and immunological factors are probably involved in adjuvant polyarthritis. The nature of the vehicle and of the mycobacterial components administered also has a major influence. It was originally assumed that arthritogenicity and adjuvanticity of mycobacterial fractions such as wax D were intimately related. Our previous findings showed that the water soluble adjuvant (WSA) of M.smegmatis which could substitute for mycobacterial cells in Freund's complete adjuvant and induce delayed hypersensitivity was not arthritogenic in the Wistar rat. We have since observed that auto-immune diseases could be elicited by WSA. Therefore experiments were repeated using the very susceptible Lewis strain. The activity of cord factor and of various mycobacterial preparations suspended in mineral or in peanut oil was also evaluated in mice and in normal or hypophysectomized rats. Our present findings confirm the absence of arthritogenicity of WSA in the Lewis strain. They also indicate that cord factor with WSA does not suffice to induce a generalized adjuvant disease, but that a mycobacterial component which could be susceptible to lysozyme treatment is required also. However, the local inflammation of the injected limb was produced by a preparation of cord factor administered in mineral or even in peanut oil. This was observed in normal or hypophysectomized rats and in Swiss mice which were not susceptible to the generalized disease.", "contents": "Adjuvant disease induced by mycobacteria, determinants of arthritogenicity. Genetic, endocrine and immunological factors are probably involved in adjuvant polyarthritis. The nature of the vehicle and of the mycobacterial components administered also has a major influence. It was originally assumed that arthritogenicity and adjuvanticity of mycobacterial fractions such as wax D were intimately related. Our previous findings showed that the water soluble adjuvant (WSA) of M.smegmatis which could substitute for mycobacterial cells in Freund's complete adjuvant and induce delayed hypersensitivity was not arthritogenic in the Wistar rat. We have since observed that auto-immune diseases could be elicited by WSA. Therefore experiments were repeated using the very susceptible Lewis strain. The activity of cord factor and of various mycobacterial preparations suspended in mineral or in peanut oil was also evaluated in mice and in normal or hypophysectomized rats. Our present findings confirm the absence of arthritogenicity of WSA in the Lewis strain. They also indicate that cord factor with WSA does not suffice to induce a generalized adjuvant disease, but that a mycobacterial component which could be susceptible to lysozyme treatment is required also. However, the local inflammation of the injected limb was produced by a preparation of cord factor administered in mineral or even in peanut oil. This was observed in normal or hypophysectomized rats and in Swiss mice which were not susceptible to the generalized disease."} {"id": "PMID:181977", "title": "Cardiac dysrhythmias in the conscious dog after surgically induced autonomic imbalance.", "content": "The ventrolateral cardiac nerve in the dog is a primary branch of the left sympathetics and represents a direct neural link between the central nervous system and the heart. Its electric excitation elicits characteristic shifts in pacemaker and tachydysrhythmias related to its explicit innervation of the inferior atrial, atrioventricular (A-V) junctional and ventricular tissues. Total denervation of the canine heart, sparing the ventrolateral cardiac nerve, produced a long-term model in which only these portions of the heart retained their sympathetic innervation. The trained unanesthetized model dog was subjected to severe exercise in order to determine the effects of elevated levels of sympathetic tone upon these important regions of the conduction system. Reproducible tachydysrhythmias were elicited in all six animals completing the regimen of periodic testing over a period of 136 to 378 days after operation. The abnormal rhythms consisted of shifting cardiac pacemakers and supraventricular A-V junctional and ventricular tachycardias with frequent premature systoles. Comparable abnormalities were not observed in a similarly tested sham-operated animal or in dogs with a totally denervated heart. The exercise-induced dysrhythmias gradually disappeared with time, presumably in relation to autonomic reinnervation of the heart. The characteristic patterns of ventrolateral cardiac nerve and upon its presumed influence upon Purkinje fiber and A-V nodal automaticity and temporal dispersion of refractoriness in myocardial tissues.", "contents": "Cardiac dysrhythmias in the conscious dog after surgically induced autonomic imbalance. The ventrolateral cardiac nerve in the dog is a primary branch of the left sympathetics and represents a direct neural link between the central nervous system and the heart. Its electric excitation elicits characteristic shifts in pacemaker and tachydysrhythmias related to its explicit innervation of the inferior atrial, atrioventricular (A-V) junctional and ventricular tissues. Total denervation of the canine heart, sparing the ventrolateral cardiac nerve, produced a long-term model in which only these portions of the heart retained their sympathetic innervation. The trained unanesthetized model dog was subjected to severe exercise in order to determine the effects of elevated levels of sympathetic tone upon these important regions of the conduction system. Reproducible tachydysrhythmias were elicited in all six animals completing the regimen of periodic testing over a period of 136 to 378 days after operation. The abnormal rhythms consisted of shifting cardiac pacemakers and supraventricular A-V junctional and ventricular tachycardias with frequent premature systoles. Comparable abnormalities were not observed in a similarly tested sham-operated animal or in dogs with a totally denervated heart. The exercise-induced dysrhythmias gradually disappeared with time, presumably in relation to autonomic reinnervation of the heart. The characteristic patterns of ventrolateral cardiac nerve and upon its presumed influence upon Purkinje fiber and A-V nodal automaticity and temporal dispersion of refractoriness in myocardial tissues."} {"id": "PMID:181978", "title": "Effect of dietary control and exercise training on daily food intake and serum lipids in postmyocardial infarction patients.", "content": "The effects of 12 weeks of exercise training without dietary control (n = 30) and exercise training with dietary control by dietition counseling (n = 30) and exercise training with dietary control by dietition counseling (n = 30) on serum cholesterol, serum triglycerides, and total substrate contents were studied in 60 postmyocardial infarction patients. Both groups showed reductions (P less than 0.01) in mean total daily kilocalories consumed (2867 +/- 82 versus 2088 +/- 77 and 2848 +/- 15 versus 1285 +/- 68, respectively); however, no significant change occurred in total body weight. The dietary control group consumed relatively more kilocalories as protein than the group without dietary control (285 of 1,285 versus 389 of 2,088, respectively) and less (P less than 0.05) as fat (443 of 1285 versus 804 of 2,089, respectively). Both groups had lower (P less than 0.01) mean daily dietary cholesterol after 12 weeks (811 +/- 44 versus 232 +/- 17 mg) versus (325 +/- 18 versus 309 +/- 23 mg, respectively). A reduction in serum cholesterol (P less than 0.05) was seen in the dietary control group (270 +/- 8 versus 243 +/- 7 mg/dl) but not in the group without dietary control (260 +/- 6 versus 261 +/- 7 mg/dl). The dietary control group had a lower mean triglyceride level (P less than 0.05) (229 +/- 24 versus 155 +/- 18 mg/dl)) but no differences were seen in the group without dietary control (189 +/- 15 versus 180 +/- 13 mg/dl). It is concluded that significant reductions in caloric intake and daily cholesterol compliment the effects of exercise training in postmyocardial infarction patients by increasing substrate protein:fat consumption ratio and by reducing serum cholesterol and triglycerides. These effects are not seen with exercise training alone.", "contents": "Effect of dietary control and exercise training on daily food intake and serum lipids in postmyocardial infarction patients. The effects of 12 weeks of exercise training without dietary control (n = 30) and exercise training with dietary control by dietition counseling (n = 30) and exercise training with dietary control by dietition counseling (n = 30) on serum cholesterol, serum triglycerides, and total substrate contents were studied in 60 postmyocardial infarction patients. Both groups showed reductions (P less than 0.01) in mean total daily kilocalories consumed (2867 +/- 82 versus 2088 +/- 77 and 2848 +/- 15 versus 1285 +/- 68, respectively); however, no significant change occurred in total body weight. The dietary control group consumed relatively more kilocalories as protein than the group without dietary control (285 of 1,285 versus 389 of 2,088, respectively) and less (P less than 0.05) as fat (443 of 1285 versus 804 of 2,089, respectively). Both groups had lower (P less than 0.01) mean daily dietary cholesterol after 12 weeks (811 +/- 44 versus 232 +/- 17 mg) versus (325 +/- 18 versus 309 +/- 23 mg, respectively). A reduction in serum cholesterol (P less than 0.05) was seen in the dietary control group (270 +/- 8 versus 243 +/- 7 mg/dl) but not in the group without dietary control (260 +/- 6 versus 261 +/- 7 mg/dl). The dietary control group had a lower mean triglyceride level (P less than 0.05) (229 +/- 24 versus 155 +/- 18 mg/dl)) but no differences were seen in the group without dietary control (189 +/- 15 versus 180 +/- 13 mg/dl). It is concluded that significant reductions in caloric intake and daily cholesterol compliment the effects of exercise training in postmyocardial infarction patients by increasing substrate protein:fat consumption ratio and by reducing serum cholesterol and triglycerides. These effects are not seen with exercise training alone."} {"id": "PMID:181979", "title": "Ultrastructure of the human breast and its disorders.", "content": "The extant literature pertaining to the ultrastructural features of disorders of the human breast is reviewed and annotated with findings derived from a personal study of 82 patients whose specimens encompassed a wide variety of such lesions. In addition, observations of lesions heretofore undescribed are presented.", "contents": "Ultrastructure of the human breast and its disorders. The extant literature pertaining to the ultrastructural features of disorders of the human breast is reviewed and annotated with findings derived from a personal study of 82 patients whose specimens encompassed a wide variety of such lesions. In addition, observations of lesions heretofore undescribed are presented."} {"id": "PMID:181980", "title": "Cytodifferentiated renal tumors occurring with Wilms' tumors of the opposite kidneys: report of two cases.", "content": "The most common differentiated renal tumor of early childhood is the congenital mesoblastic neophroma. Well-differentiated forms of Wilms' tumor may present a difficult differential diagnosis from these benign neoplasms. The cases of two patients found to have well-differentiated renal neoplasms after being treated for Wilms' tumor of the opposite kidneys are reported. The second neoplasms were composed of a benign-appearing stroma with mature skeletal muscle and completely lacked any embryonal, nephroblastic tissue. These benign-appearing neoplasms may be cytodifferentiated variants of Wilms' tumor. Though tumors of this type may have a malignant potential, there is evidence to indicate that they may be approached more conservatively than the usual nephroblastoma. In cases of bilateral Wilms' tumor, well-differentiated tumors might be treated by partial nephrectomy alone, with careful preservation of functional renal tissue.", "contents": "Cytodifferentiated renal tumors occurring with Wilms' tumors of the opposite kidneys: report of two cases. The most common differentiated renal tumor of early childhood is the congenital mesoblastic neophroma. Well-differentiated forms of Wilms' tumor may present a difficult differential diagnosis from these benign neoplasms. The cases of two patients found to have well-differentiated renal neoplasms after being treated for Wilms' tumor of the opposite kidneys are reported. The second neoplasms were composed of a benign-appearing stroma with mature skeletal muscle and completely lacked any embryonal, nephroblastic tissue. These benign-appearing neoplasms may be cytodifferentiated variants of Wilms' tumor. Though tumors of this type may have a malignant potential, there is evidence to indicate that they may be approached more conservatively than the usual nephroblastoma. In cases of bilateral Wilms' tumor, well-differentiated tumors might be treated by partial nephrectomy alone, with careful preservation of functional renal tissue."} {"id": "PMID:181981", "title": "A sensitive fluorimetric assay for serum angiotensin-converting enzyme.", "content": "A simple, rapid, highly sensitive and reproducible assay for angiotensin-converting enzyme in untreated serum is described. It is based on the conversion of the substrate analog, hippuryl-L-histidyl-L-leucine (5 mM in 0.1 M K phosphate, pH 8.3-0.3 M NaCl) to hippurate and L-histidyl-L-leucine, which is quantified spectrofluorimetrically (lamdba excitation = 360 nm; lamdba fluorescence = 500 nm) by formation of a fluorescent adduct with ophthaldialdehyde. The chloride requirement and inhibition and activation patterns correspond to those for angiotensin-converting enzyme. The Km for hippuryl-L-histidyl-L-leucine was 1.33 mM. The mean value of serum angiotensin-converting enzyme for 58 normal human subjects (mean age, 32 years; range 19-57) was 32.2 +/- 1.30 (SE), with a standard deviation of 9.87 nmol/min/ml serum. The assay is useful for the diagnosis and possible management of sarcoidosis and may have other applications in the future.", "contents": "A sensitive fluorimetric assay for serum angiotensin-converting enzyme. A simple, rapid, highly sensitive and reproducible assay for angiotensin-converting enzyme in untreated serum is described. It is based on the conversion of the substrate analog, hippuryl-L-histidyl-L-leucine (5 mM in 0.1 M K phosphate, pH 8.3-0.3 M NaCl) to hippurate and L-histidyl-L-leucine, which is quantified spectrofluorimetrically (lamdba excitation = 360 nm; lamdba fluorescence = 500 nm) by formation of a fluorescent adduct with ophthaldialdehyde. The chloride requirement and inhibition and activation patterns correspond to those for angiotensin-converting enzyme. The Km for hippuryl-L-histidyl-L-leucine was 1.33 mM. The mean value of serum angiotensin-converting enzyme for 58 normal human subjects (mean age, 32 years; range 19-57) was 32.2 +/- 1.30 (SE), with a standard deviation of 9.87 nmol/min/ml serum. The assay is useful for the diagnosis and possible management of sarcoidosis and may have other applications in the future."} {"id": "PMID:181982", "title": "Meningitis due to combined infections. Association of Haemophilus influenzae type B and Clostridium perfringens.", "content": "Haemophilus influenzae type B and Clostridium perfringens were recovered simultaneously from the cerebrospinal fluid of a patient with purulent meningitis. No antecedent history of head trauma was present to explain the coexistence of the anaerobe with Haemophilus organisms. A review of the literature on mixed meningitis indicates that no previous cases of anaerobes have been reported in uncomplicated meningitis due to multiple organisms. In addition, the recovery of clostridia is extremely unusual in the absence of an identifiable portal of entry. We have identified two additional cases of clostridia infection in the central nervous system and recommend that anaerobic organisms be considered in selected cases of meningitis.", "contents": "Meningitis due to combined infections. Association of Haemophilus influenzae type B and Clostridium perfringens. Haemophilus influenzae type B and Clostridium perfringens were recovered simultaneously from the cerebrospinal fluid of a patient with purulent meningitis. No antecedent history of head trauma was present to explain the coexistence of the anaerobe with Haemophilus organisms. A review of the literature on mixed meningitis indicates that no previous cases of anaerobes have been reported in uncomplicated meningitis due to multiple organisms. In addition, the recovery of clostridia is extremely unusual in the absence of an identifiable portal of entry. We have identified two additional cases of clostridia infection in the central nervous system and recommend that anaerobic organisms be considered in selected cases of meningitis."} {"id": "PMID:181983", "title": "Abnormal vitamin D metabolism in patients with cirrhosis.", "content": "To assess the role of hepatic function and alcohol on vitamin D metabolism, serum 25-hydroxyvitamin D (25-OHD) levels were measured in 20 healthy nonalcoholic control subjects, 31 \"inactive\" cirrhotics whose alcoholism was in remission, 8 alcoholic cirrhotics, and 15 alcoholics with normal liver function. Cirrhosis but not alcoholism, was assoicated with low serum 25-OHD levels. The aminopyrine breath test (ABT) was performed because aminopyrine, like vitamin D3, is metabolized by hepatic microsomes; the ABT correlated highly (r = 0.74, rho less than 0.01) with serum 25-OHD in the inactive cirrhotics. After an intravenous injection of 120 mug vitamin D3, serum 25-OHD rose significantly within 24 hr in 6 healthy controls and 2 patients with celiac disease but not in 6 inactive cirrhotics. The data suggest impaired 25-hydroxylation of vitamin-D impaired in patients with cirrhosis, related predominantly to the degree of hepatic dysfunction.", "contents": "Abnormal vitamin D metabolism in patients with cirrhosis. To assess the role of hepatic function and alcohol on vitamin D metabolism, serum 25-hydroxyvitamin D (25-OHD) levels were measured in 20 healthy nonalcoholic control subjects, 31 \"inactive\" cirrhotics whose alcoholism was in remission, 8 alcoholic cirrhotics, and 15 alcoholics with normal liver function. Cirrhosis but not alcoholism, was assoicated with low serum 25-OHD levels. The aminopyrine breath test (ABT) was performed because aminopyrine, like vitamin D3, is metabolized by hepatic microsomes; the ABT correlated highly (r = 0.74, rho less than 0.01) with serum 25-OHD in the inactive cirrhotics. After an intravenous injection of 120 mug vitamin D3, serum 25-OHD rose significantly within 24 hr in 6 healthy controls and 2 patients with celiac disease but not in 6 inactive cirrhotics. The data suggest impaired 25-hydroxylation of vitamin-D impaired in patients with cirrhosis, related predominantly to the degree of hepatic dysfunction."} {"id": "PMID:181984", "title": "Vaccine-associated poliomyelitis in the United States, 1961-1972.", "content": "Although poliovirus vaccines have led to a dramatic reduction in the incidence of poliomyelitis in the United States, there is evidence that vaccine-related cases have occurred in both vaccine recipients (recipient cases) and their contacts (contact cases) and that the incidence and epidemiologic characteristics of these cases in the 12-year period 1961-1972 have changed. Before 1965, there were 63 recipient cases compared with only 16 between 1965 and 1972. These latter cases were in younger persons and were more frequently associated with trivalent oral poliovirus vaccine (TOPV) than the former cases. Both groups were predominantly male and had intervals between immunization and onset of illness that clustered between 7 and 21 days. Only three contact cases were recognized before 1965, compared with 39 cases in 1965-1972. The increase was in both children and adults. Unlike recipient cases, contact cases were almost as frequent in females as in males. Evidence that the contact cases were vaccine-related included the apparent clustering between 20 and 29 days of the intervals from vaccine administration to onset of illness and the significantly increased frequency of longer intervals for contact cases in non-household members compared with contact cases in household members. The decrease in recipient cases and the increase in contact cases in 1965-1972 compared with the previous 3-year period are explained by the general curtailing of routine vaccination of adults after 1964, a switch from monovalent oral polio vaccine to TOPV, improved recognition of contact cases and a shift in emphasis from mass vaccination campaigns and communitywide programs to routine vaccination of infants.", "contents": "Vaccine-associated poliomyelitis in the United States, 1961-1972. Although poliovirus vaccines have led to a dramatic reduction in the incidence of poliomyelitis in the United States, there is evidence that vaccine-related cases have occurred in both vaccine recipients (recipient cases) and their contacts (contact cases) and that the incidence and epidemiologic characteristics of these cases in the 12-year period 1961-1972 have changed. Before 1965, there were 63 recipient cases compared with only 16 between 1965 and 1972. These latter cases were in younger persons and were more frequently associated with trivalent oral poliovirus vaccine (TOPV) than the former cases. Both groups were predominantly male and had intervals between immunization and onset of illness that clustered between 7 and 21 days. Only three contact cases were recognized before 1965, compared with 39 cases in 1965-1972. The increase was in both children and adults. Unlike recipient cases, contact cases were almost as frequent in females as in males. Evidence that the contact cases were vaccine-related included the apparent clustering between 20 and 29 days of the intervals from vaccine administration to onset of illness and the significantly increased frequency of longer intervals for contact cases in non-household members compared with contact cases in household members. The decrease in recipient cases and the increase in contact cases in 1965-1972 compared with the previous 3-year period are explained by the general curtailing of routine vaccination of adults after 1964, a switch from monovalent oral polio vaccine to TOPV, improved recognition of contact cases and a shift in emphasis from mass vaccination campaigns and communitywide programs to routine vaccination of infants."} {"id": "PMID:181985", "title": "Renal responses to PTH in patients with hormone-resistant (pseudo) hypoparathyroidism.", "content": "Five patients with pseudohypoparathyroidism were compared to normal subjects and patients with hypoparathyroidism in their ability to respond to the infusion of parathyroid hormone (PTH) by altering excretion of calcium, sodium, potassium, phosphate and bicarbonate. In patients with pseudohypoparathyroidism, impairment in renal responses to PTH was more generalized than has been recognized. The patterns of response varied from patient to patient. The most commonly observed abnormality, aside from lack of increase in urinary cyclic adenosine 5'-monophosphate (AMP) was failure to decrease the calcium to sodium clearance ratio, and indication of impaired renal calcium reabsorption. The responses which most closely approximated normal, including a normal decrease in the calcium to sodium clearance ratio, occurred in a patient (Case 1) who had the largest, although impaired, response in cyclic AMP excretion. Conversely, the most abnormal responses occurred in three patients (Cases 2, 4 and 5) who had the smallest increases in cyclic AMP excretion after the administration of PTH. The impaired renal reabsorption of calcium after the administration of PTH (lack of decrease in calcium to sodium clearance ratio) may, when present, be in part responsible for hypocalcemia.", "contents": "Renal responses to PTH in patients with hormone-resistant (pseudo) hypoparathyroidism. Five patients with pseudohypoparathyroidism were compared to normal subjects and patients with hypoparathyroidism in their ability to respond to the infusion of parathyroid hormone (PTH) by altering excretion of calcium, sodium, potassium, phosphate and bicarbonate. In patients with pseudohypoparathyroidism, impairment in renal responses to PTH was more generalized than has been recognized. The patterns of response varied from patient to patient. The most commonly observed abnormality, aside from lack of increase in urinary cyclic adenosine 5'-monophosphate (AMP) was failure to decrease the calcium to sodium clearance ratio, and indication of impaired renal calcium reabsorption. The responses which most closely approximated normal, including a normal decrease in the calcium to sodium clearance ratio, occurred in a patient (Case 1) who had the largest, although impaired, response in cyclic AMP excretion. Conversely, the most abnormal responses occurred in three patients (Cases 2, 4 and 5) who had the smallest increases in cyclic AMP excretion after the administration of PTH. The impaired renal reabsorption of calcium after the administration of PTH (lack of decrease in calcium to sodium clearance ratio) may, when present, be in part responsible for hypocalcemia."} {"id": "PMID:181988", "title": "Hydramnion and fetal renal anomalies.", "content": "Four instances of hydramnion associated with renal anomalies are reported: two patients had obstructive uropathies and two had a neoplastic type of renal dysplasia. In two infants water concentration tests revealed a defect in water-concentrating ability. It is postulated that the observed hydramnion resulted from fetal polyuria. In patients with unexplained hydramnion a search for renal anomalies is indicated.", "contents": "Hydramnion and fetal renal anomalies. Four instances of hydramnion associated with renal anomalies are reported: two patients had obstructive uropathies and two had a neoplastic type of renal dysplasia. In two infants water concentration tests revealed a defect in water-concentrating ability. It is postulated that the observed hydramnion resulted from fetal polyuria. In patients with unexplained hydramnion a search for renal anomalies is indicated."} {"id": "PMID:181989", "title": "Initiation of human parturition. IV. Demonstration of phospholipase A2 in the lysosomes of human fetal membranes.", "content": "In this study we sought to define the subcellular localization of phospholipase A2 in human fetal membranes. Others have postulated a role for decidual lysosomes in the initiation of human parturition. We hypothesized that if phospholipase A2 were localized within lysosomes of fetal membranes the accelerated expression of the activity of this enzyme could be prevented until such time as the metabolic events of parturition begin. At parturition a perturbation of the lysosomal membrane within the chorio-amnion could result in an increased release of free arachidonic acid through an accelerated activity of phospholipase A2. The results of this study suggest that at least a portion of phospholipase A2 in the chorion laeve and amnion is localized in the lysosomal fraction.", "contents": "Initiation of human parturition. IV. Demonstration of phospholipase A2 in the lysosomes of human fetal membranes. In this study we sought to define the subcellular localization of phospholipase A2 in human fetal membranes. Others have postulated a role for decidual lysosomes in the initiation of human parturition. We hypothesized that if phospholipase A2 were localized within lysosomes of fetal membranes the accelerated expression of the activity of this enzyme could be prevented until such time as the metabolic events of parturition begin. At parturition a perturbation of the lysosomal membrane within the chorio-amnion could result in an increased release of free arachidonic acid through an accelerated activity of phospholipase A2. The results of this study suggest that at least a portion of phospholipase A2 in the chorion laeve and amnion is localized in the lysosomal fraction."} {"id": "PMID:181990", "title": "Reproductive performance of women successfully treated for gestational trophoblastic tumors.", "content": "The reproductive performance of 36 women who had been successfully treated for gestational trophoblastic tumors with multiple courses of cytotoxic agents including methotrexate, 6-mercaptopurine, actinomycin D, and 6-azauridine, between 1962 and 1972, has been studied in comparison with 36 patients who had spontaneously aborted a hydatidiform mole but received no treatment and a control group consisting of 36 women attending an antenatal clinic. The majority of patients who wanted further pregnancies following chemotherapy had one or more successful conceptions. The incidence of abnormal pregnancies in the treated group was higher than that of the control group. Similarly, there was a higher number of abnormal pregnancies in the untreated mole patients when compared with the control group. This suggests that patients who develop trophoblastic tumors tend to have a poor obstetric history and that this is not significantly worsened by chemotherapy.", "contents": "Reproductive performance of women successfully treated for gestational trophoblastic tumors. The reproductive performance of 36 women who had been successfully treated for gestational trophoblastic tumors with multiple courses of cytotoxic agents including methotrexate, 6-mercaptopurine, actinomycin D, and 6-azauridine, between 1962 and 1972, has been studied in comparison with 36 patients who had spontaneously aborted a hydatidiform mole but received no treatment and a control group consisting of 36 women attending an antenatal clinic. The majority of patients who wanted further pregnancies following chemotherapy had one or more successful conceptions. The incidence of abnormal pregnancies in the treated group was higher than that of the control group. Similarly, there was a higher number of abnormal pregnancies in the untreated mole patients when compared with the control group. This suggests that patients who develop trophoblastic tumors tend to have a poor obstetric history and that this is not significantly worsened by chemotherapy."} {"id": "PMID:181991", "title": "Adrenocorticotropic hormone in human fetal blood at delivery.", "content": "Adrenocorticotropic hormone (ACTH) concentrations in umbilical arterial and venous plasma were measured in newborn infants delivered both vaginally and by cesarean section. Mean ACTH was significantly higher in the arterial (602.0 pg. per milliliter) than venous (261.5 pg. per milliliter) plasma in vaginal deliveries (pless than 0.01). Arterial plasma of babies born by elective cesarean section before initiation of labor contained less ACTH (384.7 pg. per milliliter) when compared to those delivered after labor had started (698.7 pg. per milliliter). Serial determinations of ACTH in pooled fetal blood obtained during labor showed that the average hormone titers increased significantly from first stage (295.2 pg. per milliliter) to second stage of labor (440.5 pg. per milliliter), and reached a peak at delivery (645.4 pg. per milliliter). The pituitary gland of the fetus at midtrimester contained ACTH. Possible mechanisms for fetal secretion of ACTH at delivery are discussed.", "contents": "Adrenocorticotropic hormone in human fetal blood at delivery. Adrenocorticotropic hormone (ACTH) concentrations in umbilical arterial and venous plasma were measured in newborn infants delivered both vaginally and by cesarean section. Mean ACTH was significantly higher in the arterial (602.0 pg. per milliliter) than venous (261.5 pg. per milliliter) plasma in vaginal deliveries (pless than 0.01). Arterial plasma of babies born by elective cesarean section before initiation of labor contained less ACTH (384.7 pg. per milliliter) when compared to those delivered after labor had started (698.7 pg. per milliliter). Serial determinations of ACTH in pooled fetal blood obtained during labor showed that the average hormone titers increased significantly from first stage (295.2 pg. per milliliter) to second stage of labor (440.5 pg. per milliliter), and reached a peak at delivery (645.4 pg. per milliliter). The pituitary gland of the fetus at midtrimester contained ACTH. Possible mechanisms for fetal secretion of ACTH at delivery are discussed."} {"id": "PMID:181994", "title": "Pathology of chronic Bolivian hemorrhagic fever in the rhesus monkey.", "content": "Gross and microscopic lesions of Bolivian hemorrhagic fever (BHF) are described in 10 rhesus monkeys that survived from 30 to 78 days after subcutaneous inoculation with a dose of 10(3) plaque-forming units (PFU) of Machupo virus, a dose which produces a severe and generally fatal disease. Six of the monkeys had been given low doses of homologous immune globulin when initial signs of infection appeared. Monkeys exhibited clinical signs in two phases. The initial signs of acute infection which began to appear about 1 week following inoculation included: diarrhea, depression, anorexia, dehydration, and skin rash. The survivors of this early phase of the illness usually showed improvement before relapsing into the second (or chronic) phase, which was characterized clinically by central nervous system disturbances including incoordination, tremors, convulsions, paresis, and muscle atrophy. Microscopic lesions were similar in both immune globulin-treated and untreated animals. These included widespread lymphoreticular infiltrates in the walls and adventitia of blood vessels of the brain, spinal cord, pancreas, intestine, liver kidney, adrenal, parathyroid, heart, and skeletal muscle. Diffuse lymphocytic infiltrates not confined to the vascular or perivascular tissues were present to a variable degree in many of these and other organs. Several monkeys exhibited lymphocytic inflammation of the choroid, meninges, peripheral nerves, and ganglia.", "contents": "Pathology of chronic Bolivian hemorrhagic fever in the rhesus monkey. Gross and microscopic lesions of Bolivian hemorrhagic fever (BHF) are described in 10 rhesus monkeys that survived from 30 to 78 days after subcutaneous inoculation with a dose of 10(3) plaque-forming units (PFU) of Machupo virus, a dose which produces a severe and generally fatal disease. Six of the monkeys had been given low doses of homologous immune globulin when initial signs of infection appeared. Monkeys exhibited clinical signs in two phases. The initial signs of acute infection which began to appear about 1 week following inoculation included: diarrhea, depression, anorexia, dehydration, and skin rash. The survivors of this early phase of the illness usually showed improvement before relapsing into the second (or chronic) phase, which was characterized clinically by central nervous system disturbances including incoordination, tremors, convulsions, paresis, and muscle atrophy. Microscopic lesions were similar in both immune globulin-treated and untreated animals. These included widespread lymphoreticular infiltrates in the walls and adventitia of blood vessels of the brain, spinal cord, pancreas, intestine, liver kidney, adrenal, parathyroid, heart, and skeletal muscle. Diffuse lymphocytic infiltrates not confined to the vascular or perivascular tissues were present to a variable degree in many of these and other organs. Several monkeys exhibited lymphocytic inflammation of the choroid, meninges, peripheral nerves, and ganglia."} {"id": "PMID:181996", "title": "Differences in the provision of mental health services by race.", "content": "A study of a newly mandated crisis clinic still shows the signs of a different quality of service offered to Third World clients. Black men in the present study had difficulty in obtaining the most needed and most preferred services. Reasons for the disparity in services appear to be institutional.", "contents": "Differences in the provision of mental health services by race. A study of a newly mandated crisis clinic still shows the signs of a different quality of service offered to Third World clients. Black men in the present study had difficulty in obtaining the most needed and most preferred services. Reasons for the disparity in services appear to be institutional."} {"id": "PMID:181998", "title": "Aortoenteric and paraprosthetic-enteric fistulas: radiologic findings.", "content": "Ten cases of graft-intestinal fistulas occurred in 712 patients who had undergone abdominal aortic reconstructive surgery. Radiographic abnormalities were demonstrated in eight--three by conventional barium gastrointestinal examinations and five by angiography. A high index of suspicion of the condition and an aggressive radiologic workup are recommended.", "contents": "Aortoenteric and paraprosthetic-enteric fistulas: radiologic findings. Ten cases of graft-intestinal fistulas occurred in 712 patients who had undergone abdominal aortic reconstructive surgery. Radiographic abnormalities were demonstrated in eight--three by conventional barium gastrointestinal examinations and five by angiography. A high index of suspicion of the condition and an aggressive radiologic workup are recommended."} {"id": "PMID:181999", "title": "Angiography of mediastinal parathyroid adenomas.", "content": "Two cases with mediastinal parathyroid adenomas are presented. Both patients had undergone previous unsuccessful neck explorations. Angiography correctly localized the parathyroid adenomas in each case, substantiating the value of parathyroid angiography in mediastinal tumors.", "contents": "Angiography of mediastinal parathyroid adenomas. Two cases with mediastinal parathyroid adenomas are presented. Both patients had undergone previous unsuccessful neck explorations. Angiography correctly localized the parathyroid adenomas in each case, substantiating the value of parathyroid angiography in mediastinal tumors."} {"id": "PMID:182000", "title": "Systemic to pulmonary venous communication in the superior vena caval syndrome.", "content": "A case of superior vena caval obstruction due to bronchogenic carcinoma is presented. Upper extremity venography demonstrated shunting of contrast media from systemic veins to the right pulmonary veins. This collateral pathway has been previously described in the superior vena caval syndrome. A proposed mechanism for this flow pattern is discussed.", "contents": "Systemic to pulmonary venous communication in the superior vena caval syndrome. A case of superior vena caval obstruction due to bronchogenic carcinoma is presented. Upper extremity venography demonstrated shunting of contrast media from systemic veins to the right pulmonary veins. This collateral pathway has been previously described in the superior vena caval syndrome. A proposed mechanism for this flow pattern is discussed."} {"id": "PMID:182001", "title": "Pseudocavitary granulomas of the lung.", "content": "Due to the high lipid content of the caseous material in granulomas of the lung, these lesions may radiographically mimic truly cavitated pulmonary neoplasms or granulomas. Four cases of pseudocavitation within granulomas of the lung are presented along with their clinical, radiographic, and pathologic features. In all four cases diagnosis was made only after surgery.", "contents": "Pseudocavitary granulomas of the lung. Due to the high lipid content of the caseous material in granulomas of the lung, these lesions may radiographically mimic truly cavitated pulmonary neoplasms or granulomas. Four cases of pseudocavitation within granulomas of the lung are presented along with their clinical, radiographic, and pathologic features. In all four cases diagnosis was made only after surgery."} {"id": "PMID:182002", "title": "Percutaneous spot localization of nonpalpable breast lesions.", "content": "The spot method of localization is applied to nonpalpable breast lesions detected at mammography. This percutaneous procedure is easy to perform, comfortable for the patient, and highly accurate in facilitating surgical excision of the smallest amount of breast tissue for microscopic examination.", "contents": "Percutaneous spot localization of nonpalpable breast lesions. The spot method of localization is applied to nonpalpable breast lesions detected at mammography. This percutaneous procedure is easy to perform, comfortable for the patient, and highly accurate in facilitating surgical excision of the smallest amount of breast tissue for microscopic examination."} {"id": "PMID:182003", "title": "Double-blind comparison of meglumine lodoxamate (Cholovue) and meglumine iodipamide (Cholografin).", "content": "A double-blind comparison of two intravenous cholangiocholecystographic agents of similar molecular structure, meglumine iodoxamate and meglumine iodipamide, was carried out in 90 patients. Each produced a comparably high percentage of satisfactory examinations. A similar pattern of excretion speed and intensity was noted for each, though meglumine iodoxamate appeared to be slightly more effective in patients with elevated serum bilirubin. Less evidence of hepatic toxicity and fewer and less serious adverse side effects were observed in patients given the newer agent, meglumine iodoxamate.", "contents": "Double-blind comparison of meglumine lodoxamate (Cholovue) and meglumine iodipamide (Cholografin). A double-blind comparison of two intravenous cholangiocholecystographic agents of similar molecular structure, meglumine iodoxamate and meglumine iodipamide, was carried out in 90 patients. Each produced a comparably high percentage of satisfactory examinations. A similar pattern of excretion speed and intensity was noted for each, though meglumine iodoxamate appeared to be slightly more effective in patients with elevated serum bilirubin. Less evidence of hepatic toxicity and fewer and less serious adverse side effects were observed in patients given the newer agent, meglumine iodoxamate."} {"id": "PMID:182004", "title": "Lymphoreticular hyperplasia of the stomach (pseudolymphoma).", "content": "Three histologically proved cases of gastric lymphoreticular hyperplasia with long term follow-up are reported. This condition is often confused radiologically with ulcerating carcinoma and pathologically with malignant lymphoma. The presence of a large ulcer surrounded by a mass and associated with thick rugal folds and additional gastric or duodenal ulcers is not diagnostic but should suggest the possibility of this condition.", "contents": "Lymphoreticular hyperplasia of the stomach (pseudolymphoma). Three histologically proved cases of gastric lymphoreticular hyperplasia with long term follow-up are reported. This condition is often confused radiologically with ulcerating carcinoma and pathologically with malignant lymphoma. The presence of a large ulcer surrounded by a mass and associated with thick rugal folds and additional gastric or duodenal ulcers is not diagnostic but should suggest the possibility of this condition."} {"id": "PMID:182005", "title": "Cholecystokinetic cholecystography: efficacy and tolerance study of sincalide.", "content": "The intravenous administration of sincalide, the C-terminal octapeptide fragment of cholecystokinin, affords safe and effective means for gallbladder contraction with resultant cystic and common bile duct visualization. Intravenous sincalide circumvents the problem of unpredictability of response of the gallbladder to a fatty meal and variability in the rate of release of endogenous cholecystokinin. Peak gallbladder contraction occurs earlier than with a fatty meal.", "contents": "Cholecystokinetic cholecystography: efficacy and tolerance study of sincalide. The intravenous administration of sincalide, the C-terminal octapeptide fragment of cholecystokinin, affords safe and effective means for gallbladder contraction with resultant cystic and common bile duct visualization. Intravenous sincalide circumvents the problem of unpredictability of response of the gallbladder to a fatty meal and variability in the rate of release of endogenous cholecystokinin. Peak gallbladder contraction occurs earlier than with a fatty meal."} {"id": "PMID:182006", "title": "Colonic changes of herpes zoster.", "content": "The lesions of herpes zoster of the colon were observed in three cases. Small polygonal mucosal blebs or small ulcerations involving a short segment of the colon and appearing in a reasonable time relationship with the cutaneous manifestations either in a corresponding or noncorresponding dermatome should enable diagnosis of this unusual condition. Recognition of this entity in the presence of these skin lesions should be obvious and therefore helpful in avoiding more aggressive and invasive diagnostic procedures.", "contents": "Colonic changes of herpes zoster. The lesions of herpes zoster of the colon were observed in three cases. Small polygonal mucosal blebs or small ulcerations involving a short segment of the colon and appearing in a reasonable time relationship with the cutaneous manifestations either in a corresponding or noncorresponding dermatome should enable diagnosis of this unusual condition. Recognition of this entity in the presence of these skin lesions should be obvious and therefore helpful in avoiding more aggressive and invasive diagnostic procedures."} {"id": "PMID:182007", "title": "Anomalies of the craniovertebral border.", "content": "Pertinent embryology is reviewed as a background for understanding anomalies of the craniovertebral border. These anomalies constitute a variable spectrum due either to incomplete assimilation or abnormal fusion.", "contents": "Anomalies of the craniovertebral border. Pertinent embryology is reviewed as a background for understanding anomalies of the craniovertebral border. These anomalies constitute a variable spectrum due either to incomplete assimilation or abnormal fusion."} {"id": "PMID:182008", "title": "An early rim sign in neonatal adrenal hemorrhage.", "content": "Neonatal adrenal hemorrhage can usually be diagnosed on excretory urography without resorting to surgical exploration or invasive diagnostic procedures. In the typical case an avascular mass is seen between the liver and kidney. A case is presented in which a vascular rim surrounded the avascular mass, giving an appearance similar to that of an obstructed upper pole renal duplication. This early vascular rim, not as well known as the calcified rim which develops days to weeks after the acute hemorrhage, is probably created by compression and displacement of adrenal tissue by the central hemorrhage.", "contents": "An early rim sign in neonatal adrenal hemorrhage. Neonatal adrenal hemorrhage can usually be diagnosed on excretory urography without resorting to surgical exploration or invasive diagnostic procedures. In the typical case an avascular mass is seen between the liver and kidney. A case is presented in which a vascular rim surrounded the avascular mass, giving an appearance similar to that of an obstructed upper pole renal duplication. This early vascular rim, not as well known as the calcified rim which develops days to weeks after the acute hemorrhage, is probably created by compression and displacement of adrenal tissue by the central hemorrhage."} {"id": "PMID:182009", "title": "Autonomic dysreflexia in patients with spinal cord lesions: complication of voiding cystourethrography and lleal loopography.", "content": "Autonomic dysteflexia is a pathologic reflex which occurs in patients with a spinal cord lesion above T7. The most dangerous manifestation of this reflex is marked increase in systolic and diastolic blood pressure. The trigger is the distension of the urinary bladder, urethra, rectum, or intestine. It can and does occur during radiological examinations such as cystourethrography, loopography, and probably during the barium enema. Because of possible deleterious consequences of marked hypertension, blood pressures in these patients should be continuously monitored during the examinations and appropriate measures immediately instituted should the reaction occur.", "contents": "Autonomic dysreflexia in patients with spinal cord lesions: complication of voiding cystourethrography and lleal loopography. Autonomic dysteflexia is a pathologic reflex which occurs in patients with a spinal cord lesion above T7. The most dangerous manifestation of this reflex is marked increase in systolic and diastolic blood pressure. The trigger is the distension of the urinary bladder, urethra, rectum, or intestine. It can and does occur during radiological examinations such as cystourethrography, loopography, and probably during the barium enema. Because of possible deleterious consequences of marked hypertension, blood pressures in these patients should be continuously monitored during the examinations and appropriate measures immediately instituted should the reaction occur."} {"id": "PMID:182010", "title": "Roentgenologic abnormalities of the urinary bladder secondary to Crohn's disease.", "content": "Urinary tract symptoms and signs may result from secondary involvement of the urinary bladder in patients with Crohn's disease. In a small but significant proportion of these individuals, urinary tract symptoms represent the initial or predominant mode of presentation. Such patients may be erroneously treated for primary infection of the lower urinary tract for prolonged periods before the intestinal origin of the disease process is discovered. Roentgenologic abnormalities of the urinary bladder may provide early and important clues to the correct DIAGNOSIS. The various abnormalities of the urinary bladder which may occur secondary to Crohn's disease are described and illustrated, and the roentgenologic differential diagnosis is discussed.", "contents": "Roentgenologic abnormalities of the urinary bladder secondary to Crohn's disease. Urinary tract symptoms and signs may result from secondary involvement of the urinary bladder in patients with Crohn's disease. In a small but significant proportion of these individuals, urinary tract symptoms represent the initial or predominant mode of presentation. Such patients may be erroneously treated for primary infection of the lower urinary tract for prolonged periods before the intestinal origin of the disease process is discovered. Roentgenologic abnormalities of the urinary bladder may provide early and important clues to the correct DIAGNOSIS. The various abnormalities of the urinary bladder which may occur secondary to Crohn's disease are described and illustrated, and the roentgenologic differential diagnosis is discussed."} {"id": "PMID:182011", "title": "Unilateral hematocolpos and ipsilateral renal agenesis: report of two cases and review of the literature.", "content": "Two cases are presented of a partially duplicated vagina characterized by a one-sided hematocolpos associated with renal agenesis on the same side. A review of the English literature reveals 39 previously reported cases. Invariably this complex of anomalies is seen in adolescents and young women with progressively severe abdominal pain, menstrual irregularities, and a pelvic mass. It is important to make an early accurate diagnosis since they are usually managed as having an ovarian mass and submitted to multiple laparotomies and occasionally to mutilating surgery. An analysis is presented of the salient embryologic, clinical, and radiologic features of the 41 cases gathered. The need for definitive preoperative evaluation of both the urinary tract (urography and cystoscopy) and the genital tract (hysterosalpingography) cannot be overemphasized.", "contents": "Unilateral hematocolpos and ipsilateral renal agenesis: report of two cases and review of the literature. Two cases are presented of a partially duplicated vagina characterized by a one-sided hematocolpos associated with renal agenesis on the same side. A review of the English literature reveals 39 previously reported cases. Invariably this complex of anomalies is seen in adolescents and young women with progressively severe abdominal pain, menstrual irregularities, and a pelvic mass. It is important to make an early accurate diagnosis since they are usually managed as having an ovarian mass and submitted to multiple laparotomies and occasionally to mutilating surgery. An analysis is presented of the salient embryologic, clinical, and radiologic features of the 41 cases gathered. The need for definitive preoperative evaluation of both the urinary tract (urography and cystoscopy) and the genital tract (hysterosalpingography) cannot be overemphasized."} {"id": "PMID:182012", "title": "Gallium scanning in cerebral and cranial infections.", "content": "Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, meningitis or cerebritis gave inconsistent results.", "contents": "Gallium scanning in cerebral and cranial infections. Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, meningitis or cerebritis gave inconsistent results."} {"id": "PMID:182013", "title": "Pseudocyst formation in acute pancreatitis: ultrasonographic evaluation of 99 cases.", "content": "A total of 99 patients admitted with a diagnosis of acute pancreatitis were studied by abdominal A- and B-mode ultrasonography in an effort to detect pseudocyst formation. Positive ultrasonic scans were noted in 52 cases. In three patients with positive sonography, surgical exploration did not demonstrate pseudocysts, giving a false positive rate of 8.3%. Of the negative studies four were proven incorrect at surgery or autopsy , yielding a false negative rate of 8.5%. Approximately one-fifth with cystic lesions underwent spontaneous resolution. Three additional patients with pseudocysts had spontaneous cyst-enteric fistulization demonstrated by radiography. The sensitivity and accuracy of pancreatic ultrasound demonstrated by this study established ultrasonography as the procedure of choice in detecting pseudocyst formation in patients with acute pancreatitis.", "contents": "Pseudocyst formation in acute pancreatitis: ultrasonographic evaluation of 99 cases. A total of 99 patients admitted with a diagnosis of acute pancreatitis were studied by abdominal A- and B-mode ultrasonography in an effort to detect pseudocyst formation. Positive ultrasonic scans were noted in 52 cases. In three patients with positive sonography, surgical exploration did not demonstrate pseudocysts, giving a false positive rate of 8.3%. Of the negative studies four were proven incorrect at surgery or autopsy , yielding a false negative rate of 8.5%. Approximately one-fifth with cystic lesions underwent spontaneous resolution. Three additional patients with pseudocysts had spontaneous cyst-enteric fistulization demonstrated by radiography. The sensitivity and accuracy of pancreatic ultrasound demonstrated by this study established ultrasonography as the procedure of choice in detecting pseudocyst formation in patients with acute pancreatitis."} {"id": "PMID:182014", "title": "Preoperative radiation therapy in endometrial carcinoma: preliminary report of a clinical trial.", "content": "A total of 91 patients with stage I endometrial adenocarcinoma who were referred for radiation prior to hysterectomy were randomly allocated to recieve either intracavitary or external bean irradiation. Total abdominal hysterectomy was done 4-8 weeks later. The 53 patients who received intracavitary irradiation had an actuarial 5 year disease-free survival rate of 75%; the survival rate of the 38 patients in the external beam group was 48%. Nine patients in the external beam group had recurrence or metastases compared to two in the intracavitary group. These recurrences were predominantly pelvic. Complications were also more frequent in the external beam group. These results demonstrate that intracavitary radiation is superior to external beam radiation using the regiments described.", "contents": "Preoperative radiation therapy in endometrial carcinoma: preliminary report of a clinical trial. A total of 91 patients with stage I endometrial adenocarcinoma who were referred for radiation prior to hysterectomy were randomly allocated to recieve either intracavitary or external bean irradiation. Total abdominal hysterectomy was done 4-8 weeks later. The 53 patients who received intracavitary irradiation had an actuarial 5 year disease-free survival rate of 75%; the survival rate of the 38 patients in the external beam group was 48%. Nine patients in the external beam group had recurrence or metastases compared to two in the intracavitary group. These recurrences were predominantly pelvic. Complications were also more frequent in the external beam group. These results demonstrate that intracavitary radiation is superior to external beam radiation using the regiments described."} {"id": "PMID:182015", "title": "The role of postoperative irradiation in the management of stage I adenocarcinoma of the endometrium.", "content": "A comparison of treatment protocols for endometrial carcinoma is presented. Valid conclusions regarding optimum approach are virtually precluded because of variability of such factors as clinical staging, incidence of vaginal metastases, patient selection, and histologic grade. While hysterectomy is the established definitive treatement, the superiority of adjuvant irradiation can be demonstrated only by randomized prospective studies.", "contents": "The role of postoperative irradiation in the management of stage I adenocarcinoma of the endometrium. A comparison of treatment protocols for endometrial carcinoma is presented. Valid conclusions regarding optimum approach are virtually precluded because of variability of such factors as clinical staging, incidence of vaginal metastases, patient selection, and histologic grade. While hysterectomy is the established definitive treatement, the superiority of adjuvant irradiation can be demonstrated only by randomized prospective studies."} {"id": "PMID:182016", "title": "Fast neutron beam radiotherapy of glioblastoma multiforme.", "content": "Twenty-one patients with glioblastoma multiforme were treated with fast neutron beam irradiation of the whole brain. Therapy was well tolerated up to calculated doses of 1.850 radn+y in 12-18 increments over 6 weeks. The survival rate 6 month after initiation of treatment was 62%, not significantly different from conventional photon therapy; average posttreatment survival appears to be shortened compared to photon therapy. No improvement or prolonged maintenance of existing neurologic function was observed. Autopsy findings in seven patients showed replacement of tumor by coagulative necrosis persisting at least 16 months posttreatment, paucity of tumor cells with infrequent mitosis, and suppression of macrophage response. These findings differ from those in conventionally irradiated patients. No treatment-related changes were documented by conventional gross and histologic studies of the irradiated brains distant from the tumors. Thus the deaths of patients in this study appear to be related to unexplained causes other than progressive growth of tumor.", "contents": "Fast neutron beam radiotherapy of glioblastoma multiforme. Twenty-one patients with glioblastoma multiforme were treated with fast neutron beam irradiation of the whole brain. Therapy was well tolerated up to calculated doses of 1.850 radn+y in 12-18 increments over 6 weeks. The survival rate 6 month after initiation of treatment was 62%, not significantly different from conventional photon therapy; average posttreatment survival appears to be shortened compared to photon therapy. No improvement or prolonged maintenance of existing neurologic function was observed. Autopsy findings in seven patients showed replacement of tumor by coagulative necrosis persisting at least 16 months posttreatment, paucity of tumor cells with infrequent mitosis, and suppression of macrophage response. These findings differ from those in conventionally irradiated patients. No treatment-related changes were documented by conventional gross and histologic studies of the irradiated brains distant from the tumors. Thus the deaths of patients in this study appear to be related to unexplained causes other than progressive growth of tumor."} {"id": "PMID:182017", "title": "Transformation delay of lymphocytes in patients undergoing radiation therapy.", "content": "Two types of assay systems to measure the effect of radiation on immune competence are described. The first, transformation, is measured by blast formation or uptake and incorporation of tritiated thymidine by lumphocytes. This measure is affected by a number of known cell responses to radiation such as division delay and delay in DNA synthesis. The second, called Bactec, is designed to measure lymphocyte metabolic acitivty. Data gathered on 37 patients with lung cancer show that the Bactec system provides a better index of the patient's immune status before and after radiation therapy.", "contents": "Transformation delay of lymphocytes in patients undergoing radiation therapy. Two types of assay systems to measure the effect of radiation on immune competence are described. The first, transformation, is measured by blast formation or uptake and incorporation of tritiated thymidine by lumphocytes. This measure is affected by a number of known cell responses to radiation such as division delay and delay in DNA synthesis. The second, called Bactec, is designed to measure lymphocyte metabolic acitivty. Data gathered on 37 patients with lung cancer show that the Bactec system provides a better index of the patient's immune status before and after radiation therapy."} {"id": "PMID:182018", "title": "Perforation of the nasopharynx by nasogastric intubation: a rare cause of left pleural effusion and pneumomediastinum.", "content": "A case of nasogastric tube perforation of the posterior nasopharynx producing a left pleural effusion and pneumomediastinum is reported. Findings which led to the correct diagnosis were the rapid appearance of a left pleural effusion simultaneous with the initiation of tube feedings, the intrathoracic location of the nasogastric tube, and demonstration of perforation of the posterior nasopharynx. Potentially hazardous intubation techniques are discussed.", "contents": "Perforation of the nasopharynx by nasogastric intubation: a rare cause of left pleural effusion and pneumomediastinum. A case of nasogastric tube perforation of the posterior nasopharynx producing a left pleural effusion and pneumomediastinum is reported. Findings which led to the correct diagnosis were the rapid appearance of a left pleural effusion simultaneous with the initiation of tube feedings, the intrathoracic location of the nasogastric tube, and demonstration of perforation of the posterior nasopharynx. Potentially hazardous intubation techniques are discussed."} {"id": "PMID:182019", "title": "Arthrographic diagnosis of synovial chondromatosis.", "content": "A case of synovial chondromatosis without plain film calcifications is presented. The arthrographic findings and differential diagnosis are discussed.", "contents": "Arthrographic diagnosis of synovial chondromatosis. A case of synovial chondromatosis without plain film calcifications is presented. The arthrographic findings and differential diagnosis are discussed."} {"id": "PMID:182022", "title": "Carcinoma of the urachus.", "content": "Characteristic roentgenographic and anatomical features of a mucinous adenocarcinoma of the urachus were observed in two patients. Both presented with a midline anterior abdominal mass in the supravesicular area. The tumor contained fine stippled calcification in one case. The cystogram demonstrated an irregular filling defect in the bladder dome in the other case. Ultrasonographic examination in one case was helpful in delineating the nature, size, and location of the mass in detail.", "contents": "Carcinoma of the urachus. Characteristic roentgenographic and anatomical features of a mucinous adenocarcinoma of the urachus were observed in two patients. Both presented with a midline anterior abdominal mass in the supravesicular area. The tumor contained fine stippled calcification in one case. The cystogram demonstrated an irregular filling defect in the bladder dome in the other case. Ultrasonographic examination in one case was helpful in delineating the nature, size, and location of the mass in detail."} {"id": "PMID:182024", "title": "Update on the independent radiation monitor (IRM).", "content": "The new independent radiation monitor (IRM), unlike its predecessor, is a reliable and sensitive safetly device for any radiation therapy room. It shows unequivovally that the beam is on, and it is inexpensive and simple to construct.", "contents": "Update on the independent radiation monitor (IRM). The new independent radiation monitor (IRM), unlike its predecessor, is a reliable and sensitive safetly device for any radiation therapy room. It shows unequivovally that the beam is on, and it is inexpensive and simple to construct."} {"id": "PMID:182028", "title": "The risk and accuracy of pancreatic biopsy.", "content": "Pancreatic biopsy in 171 patients produced complications in 4.7 per cent and death in 1.7 per cent. The biopsy diagnosis was confirmed in 86 per cent but was falsely negative in 14 per cent of pancreatic cancers. Frozen sections were interpreted correctly in all cases. Wedge biopsy resulted in fewer complications and fewer false-negative results than needle biopsy and is preferable except for periampullary lesions in which transduodenal needle biopsy is best. When the biopsy incision transected a pancreatic duct, suture ligation and drainage avoided complications. Open transduodenal biopsy of periampullary lesions was reliable, but the duodenotomy closure leaked in 10 per cent of the cases. Pancreatic biopsy with confirmation of malignancy should precede pancreaticoduodenectomy in most cases of suspected pancreatic cancer.", "contents": "The risk and accuracy of pancreatic biopsy. Pancreatic biopsy in 171 patients produced complications in 4.7 per cent and death in 1.7 per cent. The biopsy diagnosis was confirmed in 86 per cent but was falsely negative in 14 per cent of pancreatic cancers. Frozen sections were interpreted correctly in all cases. Wedge biopsy resulted in fewer complications and fewer false-negative results than needle biopsy and is preferable except for periampullary lesions in which transduodenal needle biopsy is best. When the biopsy incision transected a pancreatic duct, suture ligation and drainage avoided complications. Open transduodenal biopsy of periampullary lesions was reliable, but the duodenotomy closure leaked in 10 per cent of the cases. Pancreatic biopsy with confirmation of malignancy should precede pancreaticoduodenectomy in most cases of suspected pancreatic cancer."} {"id": "PMID:182029", "title": "Hepatic artery ligation and 5-fluorouracil infusion for metastatic colon carcinoma and primary hepatoma.", "content": "Nine patients with extensive bilateral hepatic metastases of colorectal cancer were treated with hepatic artery ligation and continuous infusion of 5-fluorouracil (5-FU). Silastic catheters were inserted into the hepatic artery at laparotomy, and continuous perfusion was effected by a Sigmamotor pump. There was no operative mortality or morbidity, and drug toxicity was acceptable. Dosage averaged 10 mg/kg/day and average time of infusion was sixty-three days. Liver function returned to preoperative values within two weeks in all patients, and four patients had improvement of preoperative liver function for three to six months after perfusion. Two patients had palpable regressions that lasted five months or more, and one patient had a slight palpable regression for two months. Five who are dead had a mean survival of 10.4 months after therapy, with a median survival of 11.5 months. Eight of the nine patients had significant clinical improvement following treatment. Seven patients with irresectable primary liver carcinoma were treated with continuous 5-FU infusion. A Silastic catheter was placed at laparotomy into the hepatic artery via the gastroduodenal artery. Ligation of the hepatic artery was not performed. There was no operative mortality or morbidity. Dosage averaged 10 mg/kg/day and the average time of infusion was 140 days. Significant clinical improvement was noted in six of the seven patients although this did not correlate with improvement of hepatic function. All six responding patients are still living (mean survival, 14 months). Prolongation of life with hepatic artery infusion of 5-FU has been significantly better than with any previously reported chemotherapy for this disease.", "contents": "Hepatic artery ligation and 5-fluorouracil infusion for metastatic colon carcinoma and primary hepatoma. Nine patients with extensive bilateral hepatic metastases of colorectal cancer were treated with hepatic artery ligation and continuous infusion of 5-fluorouracil (5-FU). Silastic catheters were inserted into the hepatic artery at laparotomy, and continuous perfusion was effected by a Sigmamotor pump. There was no operative mortality or morbidity, and drug toxicity was acceptable. Dosage averaged 10 mg/kg/day and average time of infusion was sixty-three days. Liver function returned to preoperative values within two weeks in all patients, and four patients had improvement of preoperative liver function for three to six months after perfusion. Two patients had palpable regressions that lasted five months or more, and one patient had a slight palpable regression for two months. Five who are dead had a mean survival of 10.4 months after therapy, with a median survival of 11.5 months. Eight of the nine patients had significant clinical improvement following treatment. Seven patients with irresectable primary liver carcinoma were treated with continuous 5-FU infusion. A Silastic catheter was placed at laparotomy into the hepatic artery via the gastroduodenal artery. Ligation of the hepatic artery was not performed. There was no operative mortality or morbidity. Dosage averaged 10 mg/kg/day and the average time of infusion was 140 days. Significant clinical improvement was noted in six of the seven patients although this did not correlate with improvement of hepatic function. All six responding patients are still living (mean survival, 14 months). Prolongation of life with hepatic artery infusion of 5-FU has been significantly better than with any previously reported chemotherapy for this disease."} {"id": "PMID:182047", "title": "Neurological complications of extraspinal.", "content": "The anatomy and physiology of the blood supply to the central nervous system from the aorta is outlined. Pertinent cases are reported, to illustrate the effect of impairment of this blood supply in producing ischemia of the brain, spinal cord, and peripheral nerves. In patients with such neurologic disease, especially if sudden in onset, a search for a circulatory basis in lesions of the aorta or its branches may be rewarding and crucial. With regard to reconstructive surgery of the aorta, certain precautions may be taken: maintenance of normotension, gentle dissection, preservation of segmental arteries when possible, bypass shunting, avoidance of prolonged aortic clamping and perhaps heparinization. Unfortunately, depending upon deficiencies in collateral circulation to the spinal cord, occasional cases of postoperative paraplegia will still occur, which are both unavoidable and unpredictable.", "contents": "Neurological complications of extraspinal. The anatomy and physiology of the blood supply to the central nervous system from the aorta is outlined. Pertinent cases are reported, to illustrate the effect of impairment of this blood supply in producing ischemia of the brain, spinal cord, and peripheral nerves. In patients with such neurologic disease, especially if sudden in onset, a search for a circulatory basis in lesions of the aorta or its branches may be rewarding and crucial. With regard to reconstructive surgery of the aorta, certain precautions may be taken: maintenance of normotension, gentle dissection, preservation of segmental arteries when possible, bypass shunting, avoidance of prolonged aortic clamping and perhaps heparinization. Unfortunately, depending upon deficiencies in collateral circulation to the spinal cord, occasional cases of postoperative paraplegia will still occur, which are both unavoidable and unpredictable."} {"id": "PMID:182048", "title": "[Myelocytic leukaemia with atypical evolution (author's transl)].", "content": "A case of myelocytic leukaemia appeared in a four year old boy. The surprisingly benign evolution until now, leds to a speculation on the possible influence exerced by chickenpox virus as a immunologic stimulant.", "contents": "[Myelocytic leukaemia with atypical evolution (author's transl)]. A case of myelocytic leukaemia appeared in a four year old boy. The surprisingly benign evolution until now, leds to a speculation on the possible influence exerced by chickenpox virus as a immunologic stimulant."} {"id": "PMID:182049", "title": "Viremia with herpes simplex type 1 in adults. Four nonfatal cases, one with features of chicken pox.", "content": "Recovery of herpes simplex virus (HSV) Type 1 from the blood buffy coat of four adults is reported for the first time. All of the patients had vesicular stomatitis and facial vesicles; two also had either keratoconjunctivitis or disseminated skin lesions. The infection was not the primary one with HSV in any of them. Two of three patients who had renal failure were receiving immunosuppressive drugs; one patient was normal except for alcoholism and diabetes. None developed signs of visceral organ infection and all recovered within 2 to 4 weeks. The findings demonstrate the occurrence of heretofore unrecognized nonfatal HSV Type 1 viremia in both healthy and immunosuppressed leukocytes, can occur regardless of the presence of serum antibody, and may or may not be associated with the disseminated lesions.", "contents": "Viremia with herpes simplex type 1 in adults. Four nonfatal cases, one with features of chicken pox. Recovery of herpes simplex virus (HSV) Type 1 from the blood buffy coat of four adults is reported for the first time. All of the patients had vesicular stomatitis and facial vesicles; two also had either keratoconjunctivitis or disseminated skin lesions. The infection was not the primary one with HSV in any of them. Two of three patients who had renal failure were receiving immunosuppressive drugs; one patient was normal except for alcoholism and diabetes. None developed signs of visceral organ infection and all recovered within 2 to 4 weeks. The findings demonstrate the occurrence of heretofore unrecognized nonfatal HSV Type 1 viremia in both healthy and immunosuppressed leukocytes, can occur regardless of the presence of serum antibody, and may or may not be associated with the disseminated lesions."} {"id": "PMID:182046", "title": "[Insulinomas in children. Histologic and ultrastructural study. (apropos of 2 cases)].", "content": "The authors report two case-histories of insulin-secreting tumors of the pancreas in children. They emphasize the rare occurence and the percularity of these tumors with regard to insulinomas in adults. The ultrastructural and histopathological examination showed: --the presence of a \"junction area\" rich in centro-acinar cells between the pancreas and the tumor, --within the tumor, the existence of exocrine elements i.e. acinar cells and more or less differentiated canalar structures. On behalf of these findings the authors discuss the problem of the histogenesis of these tumors. Is it a matter of endocrine adenomatous hyperplasia of centro-acinar origin, or of real \"apudoma\"?", "contents": "[Insulinomas in children. Histologic and ultrastructural study. (apropos of 2 cases)]. The authors report two case-histories of insulin-secreting tumors of the pancreas in children. They emphasize the rare occurence and the percularity of these tumors with regard to insulinomas in adults. The ultrastructural and histopathological examination showed: --the presence of a \"junction area\" rich in centro-acinar cells between the pancreas and the tumor, --within the tumor, the existence of exocrine elements i.e. acinar cells and more or less differentiated canalar structures. On behalf of these findings the authors discuss the problem of the histogenesis of these tumors. Is it a matter of endocrine adenomatous hyperplasia of centro-acinar origin, or of real \"apudoma\"?"} {"id": "PMID:182051", "title": "[Adsorption of enteroviruses on nitrate cellulose membranes: influence of mineral salts, detergents and calf serum (author's transl)].", "content": "The filtration through cellulose nitrate membranes of a poliovirus type II suspension in distilled water alone or with added mineral salts (NaCl, MgCl2, AlCl3) results in adsorption of the virus. The maximal adsorption is obtained with NaCl. A detergent in the virus suspension or a pretreatment of the membranes with calf serum prevents this adsorption. Elution of the adsorbed enteroviruses is achieved with alcaline and proteinaceous buffer.", "contents": "[Adsorption of enteroviruses on nitrate cellulose membranes: influence of mineral salts, detergents and calf serum (author's transl)]. The filtration through cellulose nitrate membranes of a poliovirus type II suspension in distilled water alone or with added mineral salts (NaCl, MgCl2, AlCl3) results in adsorption of the virus. The maximal adsorption is obtained with NaCl. A detergent in the virus suspension or a pretreatment of the membranes with calf serum prevents this adsorption. Elution of the adsorbed enteroviruses is achieved with alcaline and proteinaceous buffer."} {"id": "PMID:182045", "title": "[Burkitt's disease in the Ivory Coast: anatomo-clinical and epidemiologic considerations].", "content": "The authors study the epidemiological conditions of the appearance of Burkitt's disease on the Ivory Coast. This condition represents 4.12% of cancers observed in this country. From a thorough study of the differences in temperature, relative humidity, vapour pressure, hours of sunlight, amount of rainfall, they were able to pick out that equatorial forest zones are more at risk than the savannah zones. The climatic conditions in the forest render intervention by a vector plausible, either directly or indirectly via malaria or other parasitic infestations.", "contents": "[Burkitt's disease in the Ivory Coast: anatomo-clinical and epidemiologic considerations]. The authors study the epidemiological conditions of the appearance of Burkitt's disease on the Ivory Coast. This condition represents 4.12% of cancers observed in this country. From a thorough study of the differences in temperature, relative humidity, vapour pressure, hours of sunlight, amount of rainfall, they were able to pick out that equatorial forest zones are more at risk than the savannah zones. The climatic conditions in the forest render intervention by a vector plausible, either directly or indirectly via malaria or other parasitic infestations."} {"id": "PMID:182043", "title": "Sever hypertension in a child with Wilms' tumor: a case report.", "content": "Problems of management in a child with a large Wilms' tumor and severe uncontrolled hypertension presenting for anesthesia and operation included attempts to determine the etiology of the hypertension; identification of hazards produced by attempted rapid pharmacologic control of blood pressure; need for urgent operative intervention despite uncontrolled hypertension; and choice of anesthetic agent and technic.", "contents": "Sever hypertension in a child with Wilms' tumor: a case report. Problems of management in a child with a large Wilms' tumor and severe uncontrolled hypertension presenting for anesthesia and operation included attempts to determine the etiology of the hypertension; identification of hazards produced by attempted rapid pharmacologic control of blood pressure; need for urgent operative intervention despite uncontrolled hypertension; and choice of anesthetic agent and technic."} {"id": "PMID:182053", "title": "[Non-chromaffin laryngeal paraganglioma. Clinical and electron microscopical study].", "content": "The authors describe the case of a 51 year-old woman presenting with a very large laryngeal paraganglioma in the aryepiglottic fold which had passed through the cricothyroid membrane and invaled the thyroid. A crico-hyoido-pexy enabled the tumour to by completely removed and anatomo-pathological examination showed degeneration. Under electron microscopy, the ultrastructure of the tumour was similar to that of chromaffin paragangliomas. It is three years since this patient was cured.", "contents": "[Non-chromaffin laryngeal paraganglioma. Clinical and electron microscopical study]. The authors describe the case of a 51 year-old woman presenting with a very large laryngeal paraganglioma in the aryepiglottic fold which had passed through the cricothyroid membrane and invaled the thyroid. A crico-hyoido-pexy enabled the tumour to by completely removed and anatomo-pathological examination showed degeneration. Under electron microscopy, the ultrastructure of the tumour was similar to that of chromaffin paragangliomas. It is three years since this patient was cured."} {"id": "PMID:182058", "title": "Lymph nodes and vessels in primary lymphoedema. Their relative importance in aetiology.", "content": "The classification of lymphoedemas is reviewed and the various primary lymphoedemas distinguished from the secondary. The early lymphographic studies of primary lymphoedemas (many of which arise from genetic factors) probably laid undue emphasis on changes in the lymphatic vessels. Oil contrast media in leter use in lymphography have given much information onchanges in the nodes. In 89% of patients reviewed both nodes and vessels were diseased and in the majority the changes were worse in the nodes. This suggests that in many patients with primary hypoplastic lymphoedema the pathological process has arisen first in the nodes.", "contents": "Lymph nodes and vessels in primary lymphoedema. Their relative importance in aetiology. The classification of lymphoedemas is reviewed and the various primary lymphoedemas distinguished from the secondary. The early lymphographic studies of primary lymphoedemas (many of which arise from genetic factors) probably laid undue emphasis on changes in the lymphatic vessels. Oil contrast media in leter use in lymphography have given much information onchanges in the nodes. In 89% of patients reviewed both nodes and vessels were diseased and in the majority the changes were worse in the nodes. This suggests that in many patients with primary hypoplastic lymphoedema the pathological process has arisen first in the nodes."} {"id": "PMID:182054", "title": "[Embolization in the jugulo-tympanic chemodectoma. Value, indications and results].", "content": "Jugulo-tympanic chemodectomas are usually treated by means of surgical ablation and radiotherapy, these two techniques being used either in isolation or association. The recent advent of embolization, which has undergone considerable development in the field of vasular neuro-radiology within the last few years, open up new therapeutic possibilities for these vascular tumours. A study of three personal cases, followed up after a substantial lapse of time, gives a good idea of the importance of embolization in the therapeutic armoury. In fact, although embolization used alone can cause a reduction in functional symptomatology and even and objective clinical improvement (disappearance of some lesions of the cranial pairs, for exemple), it is regularly followed by repermeabilization of the various pediculi. Embolization used in isolation should therefore be reserved for patients who are inoperable for reasons for extension or associated deficiencies. Embolization appears to be of value before the operation as it results in less haemorrhage and may also be of value before radiotherapy.", "contents": "[Embolization in the jugulo-tympanic chemodectoma. Value, indications and results]. Jugulo-tympanic chemodectomas are usually treated by means of surgical ablation and radiotherapy, these two techniques being used either in isolation or association. The recent advent of embolization, which has undergone considerable development in the field of vasular neuro-radiology within the last few years, open up new therapeutic possibilities for these vascular tumours. A study of three personal cases, followed up after a substantial lapse of time, gives a good idea of the importance of embolization in the therapeutic armoury. In fact, although embolization used alone can cause a reduction in functional symptomatology and even and objective clinical improvement (disappearance of some lesions of the cranial pairs, for exemple), it is regularly followed by repermeabilization of the various pediculi. Embolization used in isolation should therefore be reserved for patients who are inoperable for reasons for extension or associated deficiencies. Embolization appears to be of value before the operation as it results in less haemorrhage and may also be of value before radiotherapy."} {"id": "PMID:182059", "title": "[Herpes virus isolated from pigeons (author's transl)].", "content": "A virus has been isolated from pigeons with the clinical symptoms of \"infectious coryza\". The virus produces numerous pocks on the chorio-allantoic membranes; livers from infected embryos have areas of necrosis. Microscopic examinations reveals basophilic and eosinophilic intranuclear inclusions. The virus produces a cytopathic effect of rounded refractile cells after 24 h with rapidly spreads throughout the monolayer. The virus is sensitive to chloroform. Electron microscopy of negatively stained lysed cell preparations shows that the virus is a herpesvirus. The strain is pathogenic for pigeons. Lesions produced by intralaryngeal inoculation consists of small necrotic foci in the laryngeal epithelium and in the liver.", "contents": "[Herpes virus isolated from pigeons (author's transl)]. A virus has been isolated from pigeons with the clinical symptoms of \"infectious coryza\". The virus produces numerous pocks on the chorio-allantoic membranes; livers from infected embryos have areas of necrosis. Microscopic examinations reveals basophilic and eosinophilic intranuclear inclusions. The virus produces a cytopathic effect of rounded refractile cells after 24 h with rapidly spreads throughout the monolayer. The virus is sensitive to chloroform. Electron microscopy of negatively stained lysed cell preparations shows that the virus is a herpesvirus. The strain is pathogenic for pigeons. Lesions produced by intralaryngeal inoculation consists of small necrotic foci in the laryngeal epithelium and in the liver."} {"id": "PMID:182055", "title": "[Chemotherapy in a case of laryngeal chemodectoma].", "content": "A case report of chemodectoma of the right aryepiglottic fold accompanied by large homolateral adenopathy, treated by cobalt-therapy and chemotherapy. The patient is clinically cured three years from the beginning of treatment. Interesting results of chemotherapy associated with radiations where the operation is refused by the patient.", "contents": "[Chemotherapy in a case of laryngeal chemodectoma]. A case report of chemodectoma of the right aryepiglottic fold accompanied by large homolateral adenopathy, treated by cobalt-therapy and chemotherapy. The patient is clinically cured three years from the beginning of treatment. Interesting results of chemotherapy associated with radiations where the operation is refused by the patient."} {"id": "PMID:182060", "title": "Superoxide dismutase (erythrocuprein) and free radicals in clinical chemistry.", "content": "Erythrocuprein (superoxide dismutase) has recently been shown to have an enzymic function towards superoxide anions. The discovery of superoxide dismutase, its mode of action, and estimation are reviewed along with a brief introduction to oxygen activation and free-radical chemistry. The formation, activity, and destruction of oxygen free radicals in white blood cells, red blood cells, and subcellular particles are discussed. (a) The production of superoxide anions by white cells during phagocytosis is thought to be advantageous for the overall bactericidal event. (b) Normal red blood cells generate low levels of superoxide anions. Increased levels of free-radical production could play a significant role in accelerating cell ageing (haemolysis). (c) Subcellular particles produce superoxide anions. These as well as organic peroxides have been implicated in drug hydroxylation reactions involving cytochrome P-450.", "contents": "Superoxide dismutase (erythrocuprein) and free radicals in clinical chemistry. Erythrocuprein (superoxide dismutase) has recently been shown to have an enzymic function towards superoxide anions. The discovery of superoxide dismutase, its mode of action, and estimation are reviewed along with a brief introduction to oxygen activation and free-radical chemistry. The formation, activity, and destruction of oxygen free radicals in white blood cells, red blood cells, and subcellular particles are discussed. (a) The production of superoxide anions by white cells during phagocytosis is thought to be advantageous for the overall bactericidal event. (b) Normal red blood cells generate low levels of superoxide anions. Increased levels of free-radical production could play a significant role in accelerating cell ageing (haemolysis). (c) Subcellular particles produce superoxide anions. These as well as organic peroxides have been implicated in drug hydroxylation reactions involving cytochrome P-450."} {"id": "PMID:182057", "title": "Mucus gland tumors of the larynx and laryngopharynx.", "content": "During the 30-year period from 1939 through 1968, 20 patients were seen who had \"minor salivary\" tumors arising in the mucus glands of the larynx or laryngopharynx. This group comprised about 3% of more than 600 patients with mucus gland tumors of the upper aerodigestive tract treated at Memorial Sloan-Kettering Cancer Center during the same interval. In each instance the tumor was malignant, and all but three of these patients were men. Location and histology of these uncommon tumors is described. Only 2 of 18 treated cases were \"cured.\" Uncontrolled cervical lymph node involvement or distant metastasis was more often the reason for treatment failure, rather than local recurrence at the primary site.", "contents": "Mucus gland tumors of the larynx and laryngopharynx. During the 30-year period from 1939 through 1968, 20 patients were seen who had \"minor salivary\" tumors arising in the mucus glands of the larynx or laryngopharynx. This group comprised about 3% of more than 600 patients with mucus gland tumors of the upper aerodigestive tract treated at Memorial Sloan-Kettering Cancer Center during the same interval. In each instance the tumor was malignant, and all but three of these patients were men. Location and histology of these uncommon tumors is described. Only 2 of 18 treated cases were \"cured.\" Uncontrolled cervical lymph node involvement or distant metastasis was more often the reason for treatment failure, rather than local recurrence at the primary site."} {"id": "PMID:182062", "title": "Evidence for the assignment of the loci AK1, AK3 and ACONs to chromosome 9 in man.", "content": "The segregation of human enzymes and chromosomes has been studied in more than 30 independent primary human-rodent somatic cell hybrids and a series of 64 subclones. The results strongly suggest that the locus determining AK1, 'red cell' adenylate kinase, is on chromosome 9 in man, and hence that the locus for the ABO blood groups and that for the Nail-patella syndrome may also be assigned to this chromosome. Evidence is presented indicating that another adenylate kinase, nucleoside triphosphate adenylate kinase, and also the soluble form of aconitase, are probably syntenic with AK1, and that the mitochondrial form of aconitase is probably not syntenic with these loci.", "contents": "Evidence for the assignment of the loci AK1, AK3 and ACONs to chromosome 9 in man. The segregation of human enzymes and chromosomes has been studied in more than 30 independent primary human-rodent somatic cell hybrids and a series of 64 subclones. The results strongly suggest that the locus determining AK1, 'red cell' adenylate kinase, is on chromosome 9 in man, and hence that the locus for the ABO blood groups and that for the Nail-patella syndrome may also be assigned to this chromosome. Evidence is presented indicating that another adenylate kinase, nucleoside triphosphate adenylate kinase, and also the soluble form of aconitase, are probably syntenic with AK1, and that the mitochondrial form of aconitase is probably not syntenic with these loci."} {"id": "PMID:182061", "title": "Pathology of lacquer thinner induced neuropathy.", "content": "Seven men aged 17 to 22 years developed severe distal symmetrical predominately motor polyneuropathy after repeated inhalation of a commercially available brand of lacquer thinner. Motor nerve conduction velocities were markedly slowed. Fascicular biopsy specimens of sural nerve showed a striking loss of myelinated nerve fibers. Prominent neurofilamentous masses resulted insegmental paranodal distention of axons with secondary thinning and retraction of myelin from the node of Ranvier. Autopsy material from one case revealed central chromatolysis of anterior horn cells in the lumbosacral enlargement and axonal swellings in the fasciculus gracilis. One or more volatile hydrocarbons contained in the lacquer thinner involved may be neurotoxic if inhaled to excess any many cause a neuropathy with characteristic pathological features.", "contents": "Pathology of lacquer thinner induced neuropathy. Seven men aged 17 to 22 years developed severe distal symmetrical predominately motor polyneuropathy after repeated inhalation of a commercially available brand of lacquer thinner. Motor nerve conduction velocities were markedly slowed. Fascicular biopsy specimens of sural nerve showed a striking loss of myelinated nerve fibers. Prominent neurofilamentous masses resulted insegmental paranodal distention of axons with secondary thinning and retraction of myelin from the node of Ranvier. Autopsy material from one case revealed central chromatolysis of anterior horn cells in the lumbosacral enlargement and axonal swellings in the fasciculus gracilis. One or more volatile hydrocarbons contained in the lacquer thinner involved may be neurotoxic if inhaled to excess any many cause a neuropathy with characteristic pathological features."} {"id": "PMID:182067", "title": "[Mutagenic action of N-nitrosodimethylurea on Actinomyces rimosus and Penicillium chrysogenum].", "content": "High mutagenic activity of N-nitrozodimethylurea (NDMU), an agent of the group of the nitrozo compounds not studied in detail was shown with respect to prototrophic and auxotrophic strains of Actinomyces rimosus, an organism producing oxytetracycline and Penicillium chrysogenum, an organism producing penicillin. The rate of direct and back mutations in the auxotrophic strain of Act. rimosus under the effect of NDMU was many times higher than that of spontaneous mutations. NDMU was used at one of the selection stages at which a more active variant of Act. rimosus was obtained. This is evident of a possible use of the mutagen for induction of variation with respect to the quantitative feature of oxytetracycline production. A great number of morphologically changed forms and biochemical mutants of Pen. chrysogenum formed under the effect of this substance. NDMU induced a mutant of Pen. chrysogenum capable of selective synthesis of 6-aminopenicillinic acid without addition of the precursor.", "contents": "[Mutagenic action of N-nitrosodimethylurea on Actinomyces rimosus and Penicillium chrysogenum]. High mutagenic activity of N-nitrozodimethylurea (NDMU), an agent of the group of the nitrozo compounds not studied in detail was shown with respect to prototrophic and auxotrophic strains of Actinomyces rimosus, an organism producing oxytetracycline and Penicillium chrysogenum, an organism producing penicillin. The rate of direct and back mutations in the auxotrophic strain of Act. rimosus under the effect of NDMU was many times higher than that of spontaneous mutations. NDMU was used at one of the selection stages at which a more active variant of Act. rimosus was obtained. This is evident of a possible use of the mutagen for induction of variation with respect to the quantitative feature of oxytetracycline production. A great number of morphologically changed forms and biochemical mutants of Pen. chrysogenum formed under the effect of this substance. NDMU induced a mutant of Pen. chrysogenum capable of selective synthesis of 6-aminopenicillinic acid without addition of the precursor."} {"id": "PMID:182068", "title": "[Pharmacology of gentamicin sulfate].", "content": "Pharmacology of gentamicin sulfate prepared at the All-Union Research Institute of Antibiotics was studied. By the paramaters of acute toxicity the drug did not differ from a Bulgarian sample of gentamicin sulfate. Under the conditions of the acute experiment on animals it was found that only high doses of gentamicin significantly exceeding the therapeutic ones induced some decrease in the arterial pressure, respiration suppression, blocking of the neuromuscle transmission in the synapses of the skeletal muscles. The latter may be eliminated by the use of calcium chloride. Under conditions of the chronic experiment with intramuscular administration of gentamicin sulfate to the animals for 4 weeks in doses equivalent to the theraputic ones for humans, impairement of the vestibular function and albuminuria often accompanied by pronounced distrophic changes in the kidney canaliculi were observed in some animals. An increase in the drug dose resulted in more pronounced distrophic changes in the kidney tissue.", "contents": "[Pharmacology of gentamicin sulfate]. Pharmacology of gentamicin sulfate prepared at the All-Union Research Institute of Antibiotics was studied. By the paramaters of acute toxicity the drug did not differ from a Bulgarian sample of gentamicin sulfate. Under the conditions of the acute experiment on animals it was found that only high doses of gentamicin significantly exceeding the therapeutic ones induced some decrease in the arterial pressure, respiration suppression, blocking of the neuromuscle transmission in the synapses of the skeletal muscles. The latter may be eliminated by the use of calcium chloride. Under conditions of the chronic experiment with intramuscular administration of gentamicin sulfate to the animals for 4 weeks in doses equivalent to the theraputic ones for humans, impairement of the vestibular function and albuminuria often accompanied by pronounced distrophic changes in the kidney canaliculi were observed in some animals. An increase in the drug dose resulted in more pronounced distrophic changes in the kidney tissue."} {"id": "PMID:182070", "title": "[Effect of inorganic phosphorus on the biosynthesis of polymyxin B].", "content": "A synthetic medium containing optimal levels of the sources of carbon, nitrogen and inorganic phosphorus and providing satisfactory yields of polymyxin B was developed for 2 strains of Bac. polymyxa 933 and VK-153. The consumption of phosphorus in the medium by the strains and the antibiotic biosynthesis levels depended on the form of phosphorus added to the medium. Optimal biosynthesis of polymyxin B was observed at lower concentration levels of soluble soluble phosphorus in the medium than the bacterial growth.", "contents": "[Effect of inorganic phosphorus on the biosynthesis of polymyxin B]. A synthetic medium containing optimal levels of the sources of carbon, nitrogen and inorganic phosphorus and providing satisfactory yields of polymyxin B was developed for 2 strains of Bac. polymyxa 933 and VK-153. The consumption of phosphorus in the medium by the strains and the antibiotic biosynthesis levels depended on the form of phosphorus added to the medium. Optimal biosynthesis of polymyxin B was observed at lower concentration levels of soluble soluble phosphorus in the medium than the bacterial growth."} {"id": "PMID:182071", "title": "[Effect of the physiological activity of Clostridium cells on their sensitivity to antibiotics].", "content": "Actively multiplicating cells of C1. perfringens proved to be more sensitive to 7-chlor-7-desoxylincomycin and rifampicin than the cells in the phase of the population dying. The bactericidal effect of the antibiotics on Clostridia vegetating at a temperature range within 37--4degrees was studied. Determination of the content of higher fatty acids in the cultivation medium with the method of gas chromatography showed that the metabolic processes in the bacterial cells went on at a temperature of 4degrees. Sensitivity of Clostridia to antibiotics at 20 and 4degrees lowered. However, all antibiotics inhibited the cell viability under such conditions. The inhibitors of the intracellular protein synthesis, i. e. rifampicin, 7-chlor-7-desoxylincomycin and morphocycline proved to be most active. The effect of beta-lactame antibiotics, i. e. cephaloridine and benzylpenicillin was reliable though lower.", "contents": "[Effect of the physiological activity of Clostridium cells on their sensitivity to antibiotics]. Actively multiplicating cells of C1. perfringens proved to be more sensitive to 7-chlor-7-desoxylincomycin and rifampicin than the cells in the phase of the population dying. The bactericidal effect of the antibiotics on Clostridia vegetating at a temperature range within 37--4degrees was studied. Determination of the content of higher fatty acids in the cultivation medium with the method of gas chromatography showed that the metabolic processes in the bacterial cells went on at a temperature of 4degrees. Sensitivity of Clostridia to antibiotics at 20 and 4degrees lowered. However, all antibiotics inhibited the cell viability under such conditions. The inhibitors of the intracellular protein synthesis, i. e. rifampicin, 7-chlor-7-desoxylincomycin and morphocycline proved to be most active. The effect of beta-lactame antibiotics, i. e. cephaloridine and benzylpenicillin was reliable though lower."} {"id": "PMID:182072", "title": "[Results of an experimental study of the pharmacokinetics of polymyxin B sulfate].", "content": "Pharmacokinetics of polymyxin B sulfate of Soviet production was studied in various species of animals with the use of different administration routes and dosage. After a single intramuscular administration of the drug to dogs in doses of 1.1 and 2.2 mg/kg the antibiotic was detected within 5 hours at the maximum level during the 1st hour. A two-fold increase of the dose was accompanied by 1.5 times increase in the antibiotic level. Repeated administrations of polymyxin B sulfate in a dose of 4.5 mg/kg did not result in an increase in the blood level as compared to a single use of the drug. When polymyxin B sulfate was administered intravenously, the concentration peak was observed in 15 minutes independent of the dosage. Later the antibiotic level decreased. The maximum level of the drug in the mice was observed 1 hour after its intramuscular administration in a dose of 8 mg/kg, the highest levels being registered in the kidney tissues and urine.", "contents": "[Results of an experimental study of the pharmacokinetics of polymyxin B sulfate]. Pharmacokinetics of polymyxin B sulfate of Soviet production was studied in various species of animals with the use of different administration routes and dosage. After a single intramuscular administration of the drug to dogs in doses of 1.1 and 2.2 mg/kg the antibiotic was detected within 5 hours at the maximum level during the 1st hour. A two-fold increase of the dose was accompanied by 1.5 times increase in the antibiotic level. Repeated administrations of polymyxin B sulfate in a dose of 4.5 mg/kg did not result in an increase in the blood level as compared to a single use of the drug. When polymyxin B sulfate was administered intravenously, the concentration peak was observed in 15 minutes independent of the dosage. Later the antibiotic level decreased. The maximum level of the drug in the mice was observed 1 hour after its intramuscular administration in a dose of 8 mg/kg, the highest levels being registered in the kidney tissues and urine."} {"id": "PMID:182073", "title": "Altered ribosomes in antibiotic-resistant mutants of Mycobacterium smegmatis.", "content": "Two alleles for viomycin-capreomycin resistance (vic) in Mycobacterium smegmatis affect ribosome structures. One (vicA) affects a component of 50S subunits and the other (vicB) affects a component of 30S subunits. The locus for neomycin-kanamycin resistance (nek), which is linked to vicA and vicB, affects a component of 30S subunits. Although the erythromycin resistance locus (ery) is linked to vic and nek, no ribosomal alterations could be detected. Mutations at the streptomycin locus (str) not linked to vic and nek caused alterations of 30S subunits.", "contents": "Altered ribosomes in antibiotic-resistant mutants of Mycobacterium smegmatis. Two alleles for viomycin-capreomycin resistance (vic) in Mycobacterium smegmatis affect ribosome structures. One (vicA) affects a component of 50S subunits and the other (vicB) affects a component of 30S subunits. The locus for neomycin-kanamycin resistance (nek), which is linked to vicA and vicB, affects a component of 30S subunits. Although the erythromycin resistance locus (ery) is linked to vic and nek, no ribosomal alterations could be detected. Mutations at the streptomycin locus (str) not linked to vic and nek caused alterations of 30S subunits."} {"id": "PMID:182074", "title": "Microtiter assay for interferon: microspectrophotometric quantitation of cytopathic effect.", "content": "This report describes an accurate, reproducible, and efficient microassay for human interferon, using a dye-uptake method to quantitate cytopathogenicity. The antiviral activity was measured by using a Gilford 300-N microsepctrophotometer, with the automatic programmer, sampler, and data lister. Two hundred interferon samples, each in a final volume of 1.0 ml, may be analyzed and recorded in 45 min. The reproducibility of a laboratory reference interferon and the human international reference B 69/19 on two different cell lines, using the model Q Oxford sampler, was found to be excellent, with the standard error of the log10 geometric mean of both references +/- 0.04 to 0.06.", "contents": "Microtiter assay for interferon: microspectrophotometric quantitation of cytopathic effect. This report describes an accurate, reproducible, and efficient microassay for human interferon, using a dye-uptake method to quantitate cytopathogenicity. The antiviral activity was measured by using a Gilford 300-N microsepctrophotometer, with the automatic programmer, sampler, and data lister. Two hundred interferon samples, each in a final volume of 1.0 ml, may be analyzed and recorded in 45 min. The reproducibility of a laboratory reference interferon and the human international reference B 69/19 on two different cell lines, using the model Q Oxford sampler, was found to be excellent, with the standard error of the log10 geometric mean of both references +/- 0.04 to 0.06."} {"id": "PMID:182085", "title": "Dapsone-induced motor polyneuropathy. A complication of prolonged treatment of subcorneal pustular dermatosis.", "content": "A motor polyneuropathy developed in a woman with subcorneal pustular dermatosis of 16 years' duration, who had received at least 300 gm of dapsone over a five-year period and 80 gm during the four-month period of progression of her neurologic symptoms. Although the patient believed her muscle power had returned to normal four months after the drug was stopped, a slight peripheral neuropathy remained. Electrodiagnostic and clinical features during the period of greatest weakness and the subsequent 16 months were consistent with a polyneuropathy of the axonal type. The neurotoxicity of dapsone appears to be dose-dependent, but the mechanism by which it occurs is unknown.", "contents": "Dapsone-induced motor polyneuropathy. A complication of prolonged treatment of subcorneal pustular dermatosis. A motor polyneuropathy developed in a woman with subcorneal pustular dermatosis of 16 years' duration, who had received at least 300 gm of dapsone over a five-year period and 80 gm during the four-month period of progression of her neurologic symptoms. Although the patient believed her muscle power had returned to normal four months after the drug was stopped, a slight peripheral neuropathy remained. Electrodiagnostic and clinical features during the period of greatest weakness and the subsequent 16 months were consistent with a polyneuropathy of the axonal type. The neurotoxicity of dapsone appears to be dose-dependent, but the mechanism by which it occurs is unknown."} {"id": "PMID:182087", "title": "Congenital rubella associated with hypsarrhythmia.", "content": "A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood.", "contents": "Congenital rubella associated with hypsarrhythmia. A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood."} {"id": "PMID:182088", "title": "Endocrinopathy in thalassaemia major.", "content": "Pituitary, adrenal, and pancreatic functions were investigated in 9 patients with thalassaemia major. 9 a.m. plasma ACTH values were 148-480 pg/ml (normal range 15-70 pg/ml). Cortisol and growth hormone response to insulin-induced hypoglycaemia was normal in all. 24-hour urinary excretions of 17-ketosteroids and 17-hydroxycorticosteroids were normal. There was normal cortisol response to intramuscular injection of ACTH. In a physiological adrenal stimulation test there was a significantly smaller response to each physiological dose of tetracosactrin. 4 patients had diabetic glucose tolerance tests--none are clinically diabetic. The mean plasma glucose utilization constant (Kgl=2-02) is significantly smaller than normal. Plasma insulin response both in the oral and the intravenous glucose tolerance test was significantly smaller than normal. The data were consistent with severe and widespread impairment of endocrine function and a plausible explanation would be iron deposition in endocrine organs. It is suggested that pituitary hyperfunction of ACTH secretion is due to target organ unresponsiveness which can be shown in its early stages only by a physiological test of the adrenal cortex. Skin pigmentation in thalassaemia seems to be due to the melanophore-stimulating effect of this raised plasma ACTH.", "contents": "Endocrinopathy in thalassaemia major. Pituitary, adrenal, and pancreatic functions were investigated in 9 patients with thalassaemia major. 9 a.m. plasma ACTH values were 148-480 pg/ml (normal range 15-70 pg/ml). Cortisol and growth hormone response to insulin-induced hypoglycaemia was normal in all. 24-hour urinary excretions of 17-ketosteroids and 17-hydroxycorticosteroids were normal. There was normal cortisol response to intramuscular injection of ACTH. In a physiological adrenal stimulation test there was a significantly smaller response to each physiological dose of tetracosactrin. 4 patients had diabetic glucose tolerance tests--none are clinically diabetic. The mean plasma glucose utilization constant (Kgl=2-02) is significantly smaller than normal. Plasma insulin response both in the oral and the intravenous glucose tolerance test was significantly smaller than normal. The data were consistent with severe and widespread impairment of endocrine function and a plausible explanation would be iron deposition in endocrine organs. It is suggested that pituitary hyperfunction of ACTH secretion is due to target organ unresponsiveness which can be shown in its early stages only by a physiological test of the adrenal cortex. Skin pigmentation in thalassaemia seems to be due to the melanophore-stimulating effect of this raised plasma ACTH."} {"id": "PMID:182089", "title": "Vitamin-D deficiency rickets in Jamaican children.", "content": "Vitamin-D deficiency is not as rare in Jamaica as previously believed. 9 children with vitamin-D deficiency rickets have been seen at the University Hospital of the West Indies during the past 5 years. All were over 3 years of age at time of presentation. Both dietary deficiency of vitamin D and lack of exposure to sunlight seem to be important causes. Children living in rural Jamaica seem to be more susceptible to the disease than those living in a city, due perhaps to more prolonged breast feeding and lack of fortified milk feeds on weaning.", "contents": "Vitamin-D deficiency rickets in Jamaican children. Vitamin-D deficiency is not as rare in Jamaica as previously believed. 9 children with vitamin-D deficiency rickets have been seen at the University Hospital of the West Indies during the past 5 years. All were over 3 years of age at time of presentation. Both dietary deficiency of vitamin D and lack of exposure to sunlight seem to be important causes. Children living in rural Jamaica seem to be more susceptible to the disease than those living in a city, due perhaps to more prolonged breast feeding and lack of fortified milk feeds on weaning."} {"id": "PMID:182090", "title": "Immunological characterization of an arylamidase (aminopeptidase) occurring in histiocytoma.", "content": "Histiocytomas display a remarkably strong proteolytic activity. Electrophoretic and immunological studies reveald that this proteolytic activity is due, at least partially, to the presence of an arylamidase, previously described as \"aminopeptidase I\". This enzyme has been identified in various tissues of ectodermal, mesodermal and entodermal origin.", "contents": "Immunological characterization of an arylamidase (aminopeptidase) occurring in histiocytoma. Histiocytomas display a remarkably strong proteolytic activity. Electrophoretic and immunological studies reveald that this proteolytic activity is due, at least partially, to the presence of an arylamidase, previously described as \"aminopeptidase I\". This enzyme has been identified in various tissues of ectodermal, mesodermal and entodermal origin."} {"id": "PMID:182091", "title": "Effects of steriod hormones on human fibroblasts in vitro. II. Antagonism by androgens of cortisol-induced inhibition.", "content": "Inhibition of dermal activity by cortisol in culture was partially reversed by two naturally occurring androgens, testosterone and dihydrotestosterone. ACTH and the androgen precursor dehydroepiandrosterone sulphate showed not such antagonistic effect. These results suggest that increased production of adrenal androgens during ACTH therapy may account for the relative absnece of 'skin-thinning' and 'steroid-bruising' which are common side-effects of corticosteroid therapy.", "contents": "Effects of steriod hormones on human fibroblasts in vitro. II. Antagonism by androgens of cortisol-induced inhibition. Inhibition of dermal activity by cortisol in culture was partially reversed by two naturally occurring androgens, testosterone and dihydrotestosterone. ACTH and the androgen precursor dehydroepiandrosterone sulphate showed not such antagonistic effect. These results suggest that increased production of adrenal androgens during ACTH therapy may account for the relative absnece of 'skin-thinning' and 'steroid-bruising' which are common side-effects of corticosteroid therapy."} {"id": "PMID:182092", "title": "Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis.", "content": "Epstein-Barr virus and cytomegalovirus antibody levels were not higher in patients with rheumatoid arthritis compared to matched controls. Delayed hypersensitivity, measured by skin test reactivity, was depressed in rheumatoid arthritis. There was no correlation between virus antibody titres and delayed hypersensitivity.", "contents": "Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis. Epstein-Barr virus and cytomegalovirus antibody levels were not higher in patients with rheumatoid arthritis compared to matched controls. Delayed hypersensitivity, measured by skin test reactivity, was depressed in rheumatoid arthritis. There was no correlation between virus antibody titres and delayed hypersensitivity."} {"id": "PMID:182094", "title": "The actions of trimetazidine on nerve and muscle cells in frogs.", "content": "The effect of trimetazidine (TMZ) on cardiac, skeletal muscle fibres and sympathetic ganglion cells in frogs were studied. In cardiac muscles, the contraction was depressed and the duration of action potentials were shortened by 1.5 mM TMZ. In skeletal muscles, the contraction induced by motor nerve stimulations was depressed by 0.3 mM TMZ, and the amplitude of end-plate potentials was decreased under this condition. The nicotinic transmission in sympathetic ganglia was inhibited by 0.003 mM TMZ, but the muscarinic transmission was not affected by 1.5 mM TMZ. In a Na-free TEA solution, prolonged action potentials (TEA potentials) of sympathetic ganglion cell, which appeared to be produced by an inward Ca movement across the membrane, were shortened by 1.5 mM TMZ. These results suggest that TMZ has a dual action, namely 1) a blocking action of nicotinic transmissions and 2) a blocking action of Ca movement during the generation of action potentials.", "contents": "The actions of trimetazidine on nerve and muscle cells in frogs. The effect of trimetazidine (TMZ) on cardiac, skeletal muscle fibres and sympathetic ganglion cells in frogs were studied. In cardiac muscles, the contraction was depressed and the duration of action potentials were shortened by 1.5 mM TMZ. In skeletal muscles, the contraction induced by motor nerve stimulations was depressed by 0.3 mM TMZ, and the amplitude of end-plate potentials was decreased under this condition. The nicotinic transmission in sympathetic ganglia was inhibited by 0.003 mM TMZ, but the muscarinic transmission was not affected by 1.5 mM TMZ. In a Na-free TEA solution, prolonged action potentials (TEA potentials) of sympathetic ganglion cell, which appeared to be produced by an inward Ca movement across the membrane, were shortened by 1.5 mM TMZ. These results suggest that TMZ has a dual action, namely 1) a blocking action of nicotinic transmissions and 2) a blocking action of Ca movement during the generation of action potentials."} {"id": "PMID:182093", "title": "[Antivariola vaccination. Technics for the mitigation of local and general reactions. Practical experience].", "content": "A technik is proposed for the attenuation of the local and general reactions produced by antivariola vaccination. The process is based on the use of \"puntiform inoculation\" and of a liophilised vaccine already decayed.", "contents": "[Antivariola vaccination. Technics for the mitigation of local and general reactions. Practical experience]. A technik is proposed for the attenuation of the local and general reactions produced by antivariola vaccination. The process is based on the use of \"puntiform inoculation\" and of a liophilised vaccine already decayed."} {"id": "PMID:182098", "title": "Polyneuropathy due to n-hexane.", "content": "In 25 years, at least eight of 50 total exposed employees in a small plant developed a mild neuropathy. Studies of urine or blood for lead, arsenic, mercury, cadmium, thallium, and antimony revealed no sign of toxic agents, but the atmosphere in one room contained toxic levels of n-hexane. The sourse was the glue used in the plant. Serum cholinesterase levels were reduced, offering a possible laboratory tests to alert clinicians to the possibility of n-hexane exposure. All patients recovered completely. Mechanical and administrative adjustments should prevent such industrial accidents.", "contents": "Polyneuropathy due to n-hexane. In 25 years, at least eight of 50 total exposed employees in a small plant developed a mild neuropathy. Studies of urine or blood for lead, arsenic, mercury, cadmium, thallium, and antimony revealed no sign of toxic agents, but the atmosphere in one room contained toxic levels of n-hexane. The sourse was the glue used in the plant. Serum cholinesterase levels were reduced, offering a possible laboratory tests to alert clinicians to the possibility of n-hexane exposure. All patients recovered completely. Mechanical and administrative adjustments should prevent such industrial accidents."} {"id": "PMID:182099", "title": "Viral ascending radiculomyelitis with severe hypoglycorrachia.", "content": "Ascending radiculomyelitis in a 52-year-old woman was accompanied by transient marked hypoglycorrachia and polymorphonuclear pleocytosis of the CSF. Examination of the CSF later in the course of illness revealed albuminocytologic dissociation. This unusual sequence of findings was associated with serologic evidence of a recent cytomegalovirus (CMV) infection. In addition, the illness was associated with a nonthrombocytopenic purpuric rash. We proposed that the rash and neurologic disease were consequences of vasculitis caused by CMV infection.", "contents": "Viral ascending radiculomyelitis with severe hypoglycorrachia. Ascending radiculomyelitis in a 52-year-old woman was accompanied by transient marked hypoglycorrachia and polymorphonuclear pleocytosis of the CSF. Examination of the CSF later in the course of illness revealed albuminocytologic dissociation. This unusual sequence of findings was associated with serologic evidence of a recent cytomegalovirus (CMV) infection. In addition, the illness was associated with a nonthrombocytopenic purpuric rash. We proposed that the rash and neurologic disease were consequences of vasculitis caused by CMV infection."} {"id": "PMID:182100", "title": "The early formation of the photosynthetic apparatus in Rhodospirillum rubrum.", "content": "The time dependent assembly of the photosynthetic apparatus was studied in Rhodospirillum rubrum after transfer of cells growing aerobically in the dark to low aeration. While bacteriochlorophyll (Bchl) cellular levels increase continuously levels of soluble cytochrome C2 do not change significantly. Absorption spectra of membranes isolated at different times after transfer reveal that incorporation of carotenoids lags behind incorporation of Bchl. However, a carotenoid fraction exhibiting spectral properties of spirilloxanthin isomers was isolated apart from membranes. This carotenoid fraction even was present in homogenates from Bchl-free, aerobically grown cells. Incorporation of U-14C-proteinhydrolyzate into membrane proteins showed that proteins are mainly formed which are specific for photosynthetic membranes. Although the proportion of reaction center (RC) Bchl per light harvesting (LH) Bchl does not change the proportions of membrane proteins present in RC and LH preparations change initially. But later on the proportions of the different proteins also reach constant values. Concerning proteins characteristic for cytoplasmic membranes a differential incorporation of label can be observed. The data indicate that the photosynthetic apparatus in Rhodospirillum rubrum is assembled through a sequential mechanism.", "contents": "The early formation of the photosynthetic apparatus in Rhodospirillum rubrum. The time dependent assembly of the photosynthetic apparatus was studied in Rhodospirillum rubrum after transfer of cells growing aerobically in the dark to low aeration. While bacteriochlorophyll (Bchl) cellular levels increase continuously levels of soluble cytochrome C2 do not change significantly. Absorption spectra of membranes isolated at different times after transfer reveal that incorporation of carotenoids lags behind incorporation of Bchl. However, a carotenoid fraction exhibiting spectral properties of spirilloxanthin isomers was isolated apart from membranes. This carotenoid fraction even was present in homogenates from Bchl-free, aerobically grown cells. Incorporation of U-14C-proteinhydrolyzate into membrane proteins showed that proteins are mainly formed which are specific for photosynthetic membranes. Although the proportion of reaction center (RC) Bchl per light harvesting (LH) Bchl does not change the proportions of membrane proteins present in RC and LH preparations change initially. But later on the proportions of the different proteins also reach constant values. Concerning proteins characteristic for cytoplasmic membranes a differential incorporation of label can be observed. The data indicate that the photosynthetic apparatus in Rhodospirillum rubrum is assembled through a sequential mechanism."} {"id": "PMID:182101", "title": "[Prognosis and treatment of idiopathic thrombocytopenic purpura in children].", "content": "The following conclusions can be drawn from the study of 55 cases of I.T.P. of childhood. 1. I.T.P. evolving more than 6 months must always be considered as chronic, the disease having in these cases few chances of recovery without splenectomy. After 6 months evolution, it is probably possible to establish a prognosis and a therapeutic approach with little risk of error. 2. Among the clinical and biological criteria noted at the onset of the disease, the intensity of thrombopenia alone is statistically different in acute and chronic I.T.P. Consequently, there are few criteria allowing the early recognition of evolution to chronic I.T.P. 3. The corticoids have no curative value in I.T.P. Prolonged corticotherapy is therefore useless in this disease. 4. As a palliative, the value of the corticoids can only be statisfactorily demonstrated in chronic I.T.P. Here it is certain in 6 cases on 16. 5. The value of corticoids for capillary resistance is evident, even in small doses. 6. Splenectomy must be considered in all cases of severe or corticodependant chronic I.T.P. Cure is obtained in most cases. 7. The contribution of immunosuppressive agents and in particular azathioprine, cannot be usefully assessed on the basis of the series studied. In the absence of decisive results, it would be worthwhile to evaluate this treatment by means of a greater number of clinical trials.", "contents": "[Prognosis and treatment of idiopathic thrombocytopenic purpura in children]. The following conclusions can be drawn from the study of 55 cases of I.T.P. of childhood. 1. I.T.P. evolving more than 6 months must always be considered as chronic, the disease having in these cases few chances of recovery without splenectomy. After 6 months evolution, it is probably possible to establish a prognosis and a therapeutic approach with little risk of error. 2. Among the clinical and biological criteria noted at the onset of the disease, the intensity of thrombopenia alone is statistically different in acute and chronic I.T.P. Consequently, there are few criteria allowing the early recognition of evolution to chronic I.T.P. 3. The corticoids have no curative value in I.T.P. Prolonged corticotherapy is therefore useless in this disease. 4. As a palliative, the value of the corticoids can only be statisfactorily demonstrated in chronic I.T.P. Here it is certain in 6 cases on 16. 5. The value of corticoids for capillary resistance is evident, even in small doses. 6. Splenectomy must be considered in all cases of severe or corticodependant chronic I.T.P. Cure is obtained in most cases. 7. The contribution of immunosuppressive agents and in particular azathioprine, cannot be usefully assessed on the basis of the series studied. In the absence of decisive results, it would be worthwhile to evaluate this treatment by means of a greater number of clinical trials."} {"id": "PMID:182102", "title": "[Sero-epidemiology of infections due to cytomegalovirus by indirect hemagglutination technic].", "content": "Applied to cytomegalovirus, the technique of indirect hemagglutination offers a good sensitivity and reliable specificity for serological testings. Improvements in the standardization are however still required. Sero-epidemiological studies performed in different groups of children and carried out with this method led to the following results: mother-child contagium, early infection in young infants, and influence of socio-economical and ethnical factors. Studies performed on pregnant women showed that the risk of infection decreased after the first pregnancy.", "contents": "[Sero-epidemiology of infections due to cytomegalovirus by indirect hemagglutination technic]. Applied to cytomegalovirus, the technique of indirect hemagglutination offers a good sensitivity and reliable specificity for serological testings. Improvements in the standardization are however still required. Sero-epidemiological studies performed in different groups of children and carried out with this method led to the following results: mother-child contagium, early infection in young infants, and influence of socio-economical and ethnical factors. Studies performed on pregnant women showed that the risk of infection decreased after the first pregnancy."} {"id": "PMID:182103", "title": "Granular cell tumors of the central nervous system of rats.", "content": "On the basis of our study of 12 cases of granular cell tumors in the brains of rats of different inbred strains, it seems that granular cell tumors are not rate in the central nervous system of untreated, aging BN/Bi rats. In none were metastases found. Awareness of the occurrence of these tumors in the central nervous system of these rats may stimulate further studies into the cellular origin of granular cell tumors that form in the central nervous system of the rat and might help to elucidate the origin of these tumors in general.", "contents": "Granular cell tumors of the central nervous system of rats. On the basis of our study of 12 cases of granular cell tumors in the brains of rats of different inbred strains, it seems that granular cell tumors are not rate in the central nervous system of untreated, aging BN/Bi rats. In none were metastases found. Awareness of the occurrence of these tumors in the central nervous system of these rats may stimulate further studies into the cellular origin of granular cell tumors that form in the central nervous system of the rat and might help to elucidate the origin of these tumors in general."} {"id": "PMID:182104", "title": "Electromyographic evaluation of human detrusor muscle activity in relation to abdominal muscle activity.", "content": "Simultaneous electromyographic (EMG) recordings from the bladder detrusor muscle and the inferior rectus abdominis muscle were made in six normal subjects, in four patients with lower motor neuron bladder disease and in two patients with an upper motor neuron type of bladder lesion. Results of the study demonstrate that the bladder electrodes do not record remote muscle activity from the abdominal muscles so that any increased detrusor electrical activity with abdominal contraction must have some other explanation such as a possible abdominal-detrusor reflex or the production of increased intra-abdominal pressure from abdominal contraction. The study also demonstrates that the detrusor EMG is of value in studying the physiology of the bladder in humans, is a safe and simple technique and is of value particularly in assessing neurogenic bladder disorders.", "contents": "Electromyographic evaluation of human detrusor muscle activity in relation to abdominal muscle activity. Simultaneous electromyographic (EMG) recordings from the bladder detrusor muscle and the inferior rectus abdominis muscle were made in six normal subjects, in four patients with lower motor neuron bladder disease and in two patients with an upper motor neuron type of bladder lesion. Results of the study demonstrate that the bladder electrodes do not record remote muscle activity from the abdominal muscles so that any increased detrusor electrical activity with abdominal contraction must have some other explanation such as a possible abdominal-detrusor reflex or the production of increased intra-abdominal pressure from abdominal contraction. The study also demonstrates that the detrusor EMG is of value in studying the physiology of the bladder in humans, is a safe and simple technique and is of value particularly in assessing neurogenic bladder disorders."} {"id": "PMID:182105", "title": "Sexual impotence: studies of the hypothalamic-pituitary-thyroid axis and the effect of oral thyrotropin-releasing factor.", "content": "Thyrotropin-releasing factor was given orally to 12 impotent patients in a dose of 43 mg daily for 4 weeks in a double-blind crossover technique and compared with placebo. TRF showed no beneficial effect over placebo. In these patients, thyroid function and the hypothalamic-pituitary-thyroid axis were examined by measuring T3, T4, and TSH before and after the TRF test. There were no pathological findings for patients included in this study.", "contents": "Sexual impotence: studies of the hypothalamic-pituitary-thyroid axis and the effect of oral thyrotropin-releasing factor. Thyrotropin-releasing factor was given orally to 12 impotent patients in a dose of 43 mg daily for 4 weeks in a double-blind crossover technique and compared with placebo. TRF showed no beneficial effect over placebo. In these patients, thyroid function and the hypothalamic-pituitary-thyroid axis were examined by measuring T3, T4, and TSH before and after the TRF test. There were no pathological findings for patients included in this study."} {"id": "PMID:182106", "title": "Hepatic adenoma. Observations after estrogen withdrawal.", "content": "A case of ruptured, benign hepatic adenoma occurred in a young woman taking oral contraceptives. Our observation of this patient after biopsy and control of hemorrhage is the subject of this report. We support the concept that these tumors may regress or remain dormant after estrogen withdrawal, and question the need for routine resection of benign hepatic adenomas. Further observations of growth patterns after estrogen withdrawal are needed.", "contents": "Hepatic adenoma. Observations after estrogen withdrawal. A case of ruptured, benign hepatic adenoma occurred in a young woman taking oral contraceptives. Our observation of this patient after biopsy and control of hemorrhage is the subject of this report. We support the concept that these tumors may regress or remain dormant after estrogen withdrawal, and question the need for routine resection of benign hepatic adenomas. Further observations of growth patterns after estrogen withdrawal are needed."} {"id": "PMID:182107", "title": "Giant axonal swelling in \"huffer's\" neuropathy.", "content": "A young man with a long history of \"huffing\" of lacquer thinner developed toxic peripheral neuropathy. Clinical improvement occurred several weeks after cessation of exposure. Substantial slowing in nerve conduction was noted. Sural nerve biopsy specimen showed (1) giant axonal swelling, (2) axonal degeneration, and (3) an increased paranodal gap. We believe that \"huffer's\" neuropathy is a primary axonal neuropathy with secondary demyelination.", "contents": "Giant axonal swelling in \"huffer's\" neuropathy. A young man with a long history of \"huffing\" of lacquer thinner developed toxic peripheral neuropathy. Clinical improvement occurred several weeks after cessation of exposure. Substantial slowing in nerve conduction was noted. Sural nerve biopsy specimen showed (1) giant axonal swelling, (2) axonal degeneration, and (3) an increased paranodal gap. We believe that \"huffer's\" neuropathy is a primary axonal neuropathy with secondary demyelination."} {"id": "PMID:182109", "title": "Multiple glomus tumors of the face and eyelid.", "content": "The glomus tumor is a benign, vascular, hamartomatous derivative of the glomus body, a normal intradermal arteriovenous anastomosis. Most glomus tumors are solitary, tender lesions of the nail bed and are found only rarely on the eyelid. Occasionally, glomus tumors assume a multiple form, wherein they are nontender. I report a unique case of multiple glomus tumors involving the face, palate, eyelid, and anterior orbit.", "contents": "Multiple glomus tumors of the face and eyelid. The glomus tumor is a benign, vascular, hamartomatous derivative of the glomus body, a normal intradermal arteriovenous anastomosis. Most glomus tumors are solitary, tender lesions of the nail bed and are found only rarely on the eyelid. Occasionally, glomus tumors assume a multiple form, wherein they are nontender. I report a unique case of multiple glomus tumors involving the face, palate, eyelid, and anterior orbit."} {"id": "PMID:182110", "title": "Glomus jugulare tumor. Disseminated form in the central nervous system.", "content": "We will describe a case of glomus jugulare tumor that illustrates the potential for multiple areas of metastasis throughout the central nervous system. Extension through the dura into the subarachnoid space allows seeding via the cerebrospinal fluid as far away as the cauda equina. We will review the usual clinical course of the tumor and will evaluate the symptoms relative to the location of extension. In this case, the symptoms related to increased intracranial pressure with brain stem compression, which progressed rapidly to cause the patient's death.", "contents": "Glomus jugulare tumor. Disseminated form in the central nervous system. We will describe a case of glomus jugulare tumor that illustrates the potential for multiple areas of metastasis throughout the central nervous system. Extension through the dura into the subarachnoid space allows seeding via the cerebrospinal fluid as far away as the cauda equina. We will review the usual clinical course of the tumor and will evaluate the symptoms relative to the location of extension. In this case, the symptoms related to increased intracranial pressure with brain stem compression, which progressed rapidly to cause the patient's death."} {"id": "PMID:182111", "title": "Effects of dibutyrylcyclic AMP on the in vitro primary response of mouse spleen cells to sheep erythrocytes.", "content": "Exogenously added N6, 02'-dibutyryladenosine-3'-5'-cyclic phsophate (DBcAMP) exerted a biphasic effect on the in vitro primary response of mouse spleen cells to sheep erythrocytes (SRBC). High concentrations of DBcAMP were markedly suppressive, whereas lower concentrations brought about significant increases in the peak numbers of antibody-forming cells. The kinetics of the response were not altered by DBcAMP. A direct effect of DBcAMP on bone-marrow derived lymphocytes was suggested because this nucleotide increased the in vitro response of \"nude\" mouse spleen cells to SRBC. The magnitude of the response, however, was considerably less than that mounted by spleen cells of normal mice. These results show that DBcAMP can have either enhancing or suppressive effects on antibody formation and these effects are dependent upon nucleotide concentration, antigen-dosage and time of assay. The effects of this cyclic nucleotide differed in two major respects from those of the synthetic polyribonucleotide adjuvant, polyadenylic acid-polyuridylic acid (poly A:U) complexes. Thus poly (A:U) decreased the time of peak response in vitro but did not increase the magnitude of the response.", "contents": "Effects of dibutyrylcyclic AMP on the in vitro primary response of mouse spleen cells to sheep erythrocytes. Exogenously added N6, 02'-dibutyryladenosine-3'-5'-cyclic phsophate (DBcAMP) exerted a biphasic effect on the in vitro primary response of mouse spleen cells to sheep erythrocytes (SRBC). High concentrations of DBcAMP were markedly suppressive, whereas lower concentrations brought about significant increases in the peak numbers of antibody-forming cells. The kinetics of the response were not altered by DBcAMP. A direct effect of DBcAMP on bone-marrow derived lymphocytes was suggested because this nucleotide increased the in vitro response of \"nude\" mouse spleen cells to SRBC. The magnitude of the response, however, was considerably less than that mounted by spleen cells of normal mice. These results show that DBcAMP can have either enhancing or suppressive effects on antibody formation and these effects are dependent upon nucleotide concentration, antigen-dosage and time of assay. The effects of this cyclic nucleotide differed in two major respects from those of the synthetic polyribonucleotide adjuvant, polyadenylic acid-polyuridylic acid (poly A:U) complexes. Thus poly (A:U) decreased the time of peak response in vitro but did not increase the magnitude of the response."} {"id": "PMID:182115", "title": "[Our experiences in the treatment of acute leukemias in children].", "content": "43 children suffering of acute leucaemia were treated in University Children's Hospital Belgrade during the period of 1969- april 1975. 39 patients were treated as acute lymphoblastic leucaemia (90,7%), and 4 patients as acute nonlymphoblastic leucaemia (9,3%). Complete remission of 34 patients treated as ALL by protocol PARIS 06 was established in 94,1%. All 5 patients suffering of ALL, treated by protocol PARIS 01 LA 72 had complete remission. 85,7 patients treated by protocol 06 AL 66 survived one year. 53,5% patients survived two years, 14,2% three years, and 3,5% survived four years. These facts are not final, because 35% patients are still alive. From 5 patients treated by protocol 01 AL 72 4 patinets are in complete remission, but this period is too short to per mit any conclusion. Meadle survival time for patients suffering of ANLL is 7,5 months. One patient is in complete remission for already 9 months.", "contents": "[Our experiences in the treatment of acute leukemias in children]. 43 children suffering of acute leucaemia were treated in University Children's Hospital Belgrade during the period of 1969- april 1975. 39 patients were treated as acute lymphoblastic leucaemia (90,7%), and 4 patients as acute nonlymphoblastic leucaemia (9,3%). Complete remission of 34 patients treated as ALL by protocol PARIS 06 was established in 94,1%. All 5 patients suffering of ALL, treated by protocol PARIS 01 LA 72 had complete remission. 85,7 patients treated by protocol 06 AL 66 survived one year. 53,5% patients survived two years, 14,2% three years, and 3,5% survived four years. These facts are not final, because 35% patients are still alive. From 5 patients treated by protocol 01 AL 72 4 patinets are in complete remission, but this period is too short to per mit any conclusion. Meadle survival time for patients suffering of ANLL is 7,5 months. One patient is in complete remission for already 9 months."} {"id": "PMID:182116", "title": "Inhibition of spinach phosphoribulokinase by DL-glyceraldehyde.", "content": "Spinach chloroplast phosphoribulokinase is inhibited by DL-glyceraldehyde. The inhibition is non-competitive with respect to ribulose 5-phosphate (Ki 19mM) and ATP (Ki 20mM). The inhibition is discussed in relation to a previously reported inhibition of CO2 assimilation in intact and envelope-free chloroplasts by DL-glyceraldehyde. It is concluded that the inhibition of phosphoribulokinase is insufficient to account for the inhibition, by DL-glyceraldehyde, of O2 evolution with ribose 5-phosphate as substrate and that a further site of inhibition is also present in this system.", "contents": "Inhibition of spinach phosphoribulokinase by DL-glyceraldehyde. Spinach chloroplast phosphoribulokinase is inhibited by DL-glyceraldehyde. The inhibition is non-competitive with respect to ribulose 5-phosphate (Ki 19mM) and ATP (Ki 20mM). The inhibition is discussed in relation to a previously reported inhibition of CO2 assimilation in intact and envelope-free chloroplasts by DL-glyceraldehyde. It is concluded that the inhibition of phosphoribulokinase is insufficient to account for the inhibition, by DL-glyceraldehyde, of O2 evolution with ribose 5-phosphate as substrate and that a further site of inhibition is also present in this system."} {"id": "PMID:182117", "title": "Electron transfer between soluble and immobilized mammalian cytochrome c. Equilibrium and kinetic studies on immobilized cytochrome c.", "content": "Horse heart cytochrome c was covalently bound to Sepharose 4B and its redox properties were measured under various experimental conditions. The equilibrium constant for the electron exchange between the oxidized and the reduced form of cytochrome c when one of the two forms was in the semi-solid state and the other one in solution was close to 1. Matrix-bound ferrocytochrome c is very stable to autoxidation and is not oxidized by O2 even in the presence of mammalian cytochrome oxidase. Oxidation occurs if catalytic amounts of soluble cytochrome c are added to the reaction mixture. The rate of oxidation of matrix-bound ferrocytochrome c in the presence of cytochrome oxidase and catalytic amounts of soluble cytochrome c may be correlated with the rate of electron transfer between soluble and matrix-bound cytochrome c. This rate is more than two orders of magnitude lower than that reported for the homonuclear (between identical species) electron transfer in solution.", "contents": "Electron transfer between soluble and immobilized mammalian cytochrome c. Equilibrium and kinetic studies on immobilized cytochrome c. Horse heart cytochrome c was covalently bound to Sepharose 4B and its redox properties were measured under various experimental conditions. The equilibrium constant for the electron exchange between the oxidized and the reduced form of cytochrome c when one of the two forms was in the semi-solid state and the other one in solution was close to 1. Matrix-bound ferrocytochrome c is very stable to autoxidation and is not oxidized by O2 even in the presence of mammalian cytochrome oxidase. Oxidation occurs if catalytic amounts of soluble cytochrome c are added to the reaction mixture. The rate of oxidation of matrix-bound ferrocytochrome c in the presence of cytochrome oxidase and catalytic amounts of soluble cytochrome c may be correlated with the rate of electron transfer between soluble and matrix-bound cytochrome c. This rate is more than two orders of magnitude lower than that reported for the homonuclear (between identical species) electron transfer in solution."} {"id": "PMID:182118", "title": "Inhibition of glycolytic enzymes by 2-phosphotartronate.", "content": "2-Phosphotartronate has been synthesized by permanganate oxidation of glycerol 2-phosphate and has been tested as an inhibitor of five glycolytic enzymes that bind phosphoglycerate or phosphoglycollate. Competitive inhibition of rabbit muscle phosphoglycerate mutase, enolase and pyruvate kinase was observed. Triose phosphate isomerase and 3-phosphoglycerate kinase were not inhibited.", "contents": "Inhibition of glycolytic enzymes by 2-phosphotartronate. 2-Phosphotartronate has been synthesized by permanganate oxidation of glycerol 2-phosphate and has been tested as an inhibitor of five glycolytic enzymes that bind phosphoglycerate or phosphoglycollate. Competitive inhibition of rabbit muscle phosphoglycerate mutase, enolase and pyruvate kinase was observed. Triose phosphate isomerase and 3-phosphoglycerate kinase were not inhibited."} {"id": "PMID:182119", "title": "Enzymic formation of Glycerol 1:2-cyclic phosphate.", "content": "Glycerol 1:2-cyclic phosphate is released simultaneously with glycerophosphate when kidney glycerophosphinicocholine diesterase (EC 3.1.4.2) acts on glycerylphosphorylcholine and glycerylphosphorylethanolamine. The percentage of cyclic phosphate ester formed is increased at pH values below the optimum and is decreased when Mg2+ or Ca2+ is added to stimulate the reaction.", "contents": "Enzymic formation of Glycerol 1:2-cyclic phosphate. Glycerol 1:2-cyclic phosphate is released simultaneously with glycerophosphate when kidney glycerophosphinicocholine diesterase (EC 3.1.4.2) acts on glycerylphosphorylcholine and glycerylphosphorylethanolamine. The percentage of cyclic phosphate ester formed is increased at pH values below the optimum and is decreased when Mg2+ or Ca2+ is added to stimulate the reaction."} {"id": "PMID:182120", "title": "The fluidity of normal and virus-transformed cell plasma membrane.", "content": "1. The phospholipid composition and cholesterol/phospholipid ratio of plasma membrane is the same in normal as in transformed BHK (baby-hamster kidney) cells; no significant difference in length or degree of unsaturation of the contributing acyl chains is apparent. 2. The turnover of acetate-labelled phosphatidylcholine species in the plasma membrane of normal and transformed BHK cells is the same. 3. Intramembranous particles of normal and transformed 3T3-cell plasma membrane are randomly distributed, whether at 4degreesC or at 37degreesC, in sparse or in dense cultures. There is no correlation between distribution of particles and the movement of concanavalin A receptor sites. 4. It is concluded that transformation of fibroblastic cells by oncogenic viruses does not lead to major changes in the lipid fluidity of the plasma membrane. 5. Details of the phospholipid composition of nuclei, mitochondria and endoplasmic reticulum in normal and transformed BHK cells have been deposited as Supplementary Publication SUP 50061 (5 pages) at the British Library Lending Division, Boston, Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1976) 153, 5.", "contents": "The fluidity of normal and virus-transformed cell plasma membrane. 1. The phospholipid composition and cholesterol/phospholipid ratio of plasma membrane is the same in normal as in transformed BHK (baby-hamster kidney) cells; no significant difference in length or degree of unsaturation of the contributing acyl chains is apparent. 2. The turnover of acetate-labelled phosphatidylcholine species in the plasma membrane of normal and transformed BHK cells is the same. 3. Intramembranous particles of normal and transformed 3T3-cell plasma membrane are randomly distributed, whether at 4degreesC or at 37degreesC, in sparse or in dense cultures. There is no correlation between distribution of particles and the movement of concanavalin A receptor sites. 4. It is concluded that transformation of fibroblastic cells by oncogenic viruses does not lead to major changes in the lipid fluidity of the plasma membrane. 5. Details of the phospholipid composition of nuclei, mitochondria and endoplasmic reticulum in normal and transformed BHK cells have been deposited as Supplementary Publication SUP 50061 (5 pages) at the British Library Lending Division, Boston, Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1976) 153, 5."} {"id": "PMID:182121", "title": "Identification and properties of renal mineralocorticoid receptors in relation to glucocorticoid binders in rat liver and kidney.", "content": "The binding of the natural mineralocorticoid aldosterone and the glucocorticoid corticosterone to macromolecules in rat liver and kidney cytoplasmic fractions was compared by various chromatographic procedures. Equilibration of kidney cytosol with 10nM-aldosterone, either alone or in the presence of a competing steroid, was ideal for ionexchange chromatography of DEAE-cellulose DE-52, and revealed the presence of four sorts of binding components. One of these, eluted in the 0.001M-phosphate pre-wash, and another, less abundant, forming a peak at 0.006M-phosphate, did not bind corticosterone at equimolar concentrations, and appear to constitute the mineralocorticoid-specific 'MR' receptor in rat kidney. They could not be detected in the liver. Radioactivity eluted in the 0.02 and 0.06M-phosphate regions on DEAE-cellulose DE-52 appears to be due to [3H]aldosterone binding to glucocorticoid-specific 'GR' receptors and to transcortin respectively, since labelling was greater with corticosterone even at 10 nM than with the mineralocorticoid at 100nM and since [14C]corticosterone bound to blood serum transcortin was always co-chromatographed in the 0.06M-phosphate region. These two components appear to be identical with those in the liver and could be labelled maximally only by 100nM-corticosterone. The separation between specific mineralo- and glucocorticoid-binding species was less clear when chromatography was attempted on DEAE-Sephadex A-50 columns, possibly because of disaggregation into subunits in the presence of the high KC1 concentrations required for elution. Competitive binding followed by filtration through Sephadex G-200 gel indicated that cellular MR binders, unlike GR receptors, exist mostly as high-molecular-weight aggregates, although both appear to exhibit a comparable monomeric molecular weight of approx. 67000.", "contents": "Identification and properties of renal mineralocorticoid receptors in relation to glucocorticoid binders in rat liver and kidney. The binding of the natural mineralocorticoid aldosterone and the glucocorticoid corticosterone to macromolecules in rat liver and kidney cytoplasmic fractions was compared by various chromatographic procedures. Equilibration of kidney cytosol with 10nM-aldosterone, either alone or in the presence of a competing steroid, was ideal for ionexchange chromatography of DEAE-cellulose DE-52, and revealed the presence of four sorts of binding components. One of these, eluted in the 0.001M-phosphate pre-wash, and another, less abundant, forming a peak at 0.006M-phosphate, did not bind corticosterone at equimolar concentrations, and appear to constitute the mineralocorticoid-specific 'MR' receptor in rat kidney. They could not be detected in the liver. Radioactivity eluted in the 0.02 and 0.06M-phosphate regions on DEAE-cellulose DE-52 appears to be due to [3H]aldosterone binding to glucocorticoid-specific 'GR' receptors and to transcortin respectively, since labelling was greater with corticosterone even at 10 nM than with the mineralocorticoid at 100nM and since [14C]corticosterone bound to blood serum transcortin was always co-chromatographed in the 0.06M-phosphate region. These two components appear to be identical with those in the liver and could be labelled maximally only by 100nM-corticosterone. The separation between specific mineralo- and glucocorticoid-binding species was less clear when chromatography was attempted on DEAE-Sephadex A-50 columns, possibly because of disaggregation into subunits in the presence of the high KC1 concentrations required for elution. Competitive binding followed by filtration through Sephadex G-200 gel indicated that cellular MR binders, unlike GR receptors, exist mostly as high-molecular-weight aggregates, although both appear to exhibit a comparable monomeric molecular weight of approx. 67000."} {"id": "PMID:182122", "title": "Role of membranes in bile formation. Comparison of the composition of bile and a liver bile-canalicular plasma-membrane subfraction.", "content": "1. Enzymes, proteins, glycoproteins and lipids of rodent bile were compared with those of a plasma-membrane subfraction originating from the hepatocyte bile-canalicular membrane. 2. Three bile-canalicular glycoprotein enzyme activities were detected in bile. Comparison of the pH optimum and immunoinhibition properties of membrane and bile 5'-nucleotidase activity indicated that they were the same enzyme. Correspondence between membrane and bile alkaline phosphodiesterases also suggested that they were the same enzymes. Activities of Mg2+-stimulated adenosine triphosphatase, a lipid-dependent intrinsic membrane protein, and galactosyltransferase, a Golgi membrane marker, were not detected in bile. 3. Rodent bile contained 15 polypeptide bands that differed radically from those of bile-canalicular membranes. Bands that may correspond in molecular weight to liver plasma-membrane glycoproteins were present at low staining intensities in bile. A major protein of apparent molecular weight 49 500 was present, and albumin was detected by immunodiffusion. 4. The lipid composition of bile and bile-canalicular membrane also differed. Phosphatidylcholine accounted for 82% of rat bile phospholipids, and only trace amounts of phosphatidylinositol, phosphatidylserine and sphingomyelin were present. 5. The results indicate that in healthy animals, the bile-canalicular membrane is refractory to the action of bile acids during the secretory process. The presence of only small amounts of bile-canalicular membrane components, especially glycoprotein enzymes located at the outer face of the membrane, suggests that these are released from the membrane by bile acids after secretion of bile into the canalicular spaces.", "contents": "Role of membranes in bile formation. Comparison of the composition of bile and a liver bile-canalicular plasma-membrane subfraction. 1. Enzymes, proteins, glycoproteins and lipids of rodent bile were compared with those of a plasma-membrane subfraction originating from the hepatocyte bile-canalicular membrane. 2. Three bile-canalicular glycoprotein enzyme activities were detected in bile. Comparison of the pH optimum and immunoinhibition properties of membrane and bile 5'-nucleotidase activity indicated that they were the same enzyme. Correspondence between membrane and bile alkaline phosphodiesterases also suggested that they were the same enzymes. Activities of Mg2+-stimulated adenosine triphosphatase, a lipid-dependent intrinsic membrane protein, and galactosyltransferase, a Golgi membrane marker, were not detected in bile. 3. Rodent bile contained 15 polypeptide bands that differed radically from those of bile-canalicular membranes. Bands that may correspond in molecular weight to liver plasma-membrane glycoproteins were present at low staining intensities in bile. A major protein of apparent molecular weight 49 500 was present, and albumin was detected by immunodiffusion. 4. The lipid composition of bile and bile-canalicular membrane also differed. Phosphatidylcholine accounted for 82% of rat bile phospholipids, and only trace amounts of phosphatidylinositol, phosphatidylserine and sphingomyelin were present. 5. The results indicate that in healthy animals, the bile-canalicular membrane is refractory to the action of bile acids during the secretory process. The presence of only small amounts of bile-canalicular membrane components, especially glycoprotein enzymes located at the outer face of the membrane, suggests that these are released from the membrane by bile acids after secretion of bile into the canalicular spaces."} {"id": "PMID:182123", "title": "Renin substrate in granules from rat kidney cortex.", "content": "1. Subcellular fractions of rat kidney cortex generated angiotensin I continuously over 2h when incubated at 37degreesC with rat renin, indicating the presence of renin substrate within cells in the renal cortex. 2. Renin substrate was located in highest specific concentration in particulate fractions. The particles containing renin substrate had a sedimentation velocity slightly lower than mitochondria and renin granules but greater than the microsomal fraction. 3. Isopycnic gradient centrifugation indicated a density of 1.190g/ml for the particles containing renin substrate, compared with 1.201 for renin granules, 1.177 for mitochondria, and 1.170 and 1.230 for lysosomes in the heavy-granule fraction. 4. In the liver, renin substrate was also found in particles, but these had a lower sedimentation rate than those from the kidney. 5. The molecular weights of renin substrate in kidney and liver granules and rat plasma were similar, namely 61000-62000. 6. On the basis of these biochemical findings, a mechanism for the intrarenal production of angiotensin, incorporating a subcellular reaction scheme, is proposed.", "contents": "Renin substrate in granules from rat kidney cortex. 1. Subcellular fractions of rat kidney cortex generated angiotensin I continuously over 2h when incubated at 37degreesC with rat renin, indicating the presence of renin substrate within cells in the renal cortex. 2. Renin substrate was located in highest specific concentration in particulate fractions. The particles containing renin substrate had a sedimentation velocity slightly lower than mitochondria and renin granules but greater than the microsomal fraction. 3. Isopycnic gradient centrifugation indicated a density of 1.190g/ml for the particles containing renin substrate, compared with 1.201 for renin granules, 1.177 for mitochondria, and 1.170 and 1.230 for lysosomes in the heavy-granule fraction. 4. In the liver, renin substrate was also found in particles, but these had a lower sedimentation rate than those from the kidney. 5. The molecular weights of renin substrate in kidney and liver granules and rat plasma were similar, namely 61000-62000. 6. On the basis of these biochemical findings, a mechanism for the intrarenal production of angiotensin, incorporating a subcellular reaction scheme, is proposed."} {"id": "PMID:182124", "title": "Development and properties of fructose 1,6-bisphosphatase in the endosperm of castor-bean seedlings.", "content": "1. The activity of fructose 1,6-bisphosphatase (EC 3.1.3.11) in the fatty endosperm of castor bean (Ricinus communis) increases 25-fold during germination and then declines. The developmental pattern follows that of catalase, a marker enzyme for gluconeogenesis in this tissue. 2. The enzyme at its peak of development was partially purified, and its properties were studied. It has an optimal activity at neutral pH (7.0-8.0). The apparent Km value for fructose 1,6-bisphosphate is 3.8 X 10(-5) M. The activity is inhibited by AMP allosterically with an apparent Ki value of 2.2 X 10(-4) M. The enzyme hydrolyses fructose 1,6-bisphosphate and not ribulose 1,5-bisphosphate or sedoehptulose 1,7-bisphosphate. 3. Treatment of the partially purified enzyme with acid leads to an 80% decrease in activity. The remaining activity is insensitive to AMP and has optimal activity at pH 6.7 and a high apparent Km value (2.5 X 10(-4) M) for fructose 1.6-bisphosphate. Enzyme extracted from the tissue with water instead of buffer has a similar modification. The effect of acid explains the discrepancies between this report and previous ones on the properties of the enzyme in this tissue. 4. The storage tissues of various fatty seedlings all contain a 'neutral' fructose 1,6-bisphosphatase. The activities of the enzyme from some of the tissues are inhibited by AMP. 5. The properties of the enzyme in fatty seedlings and in green leaves are discussed in comparison with that in animal tissues.", "contents": "Development and properties of fructose 1,6-bisphosphatase in the endosperm of castor-bean seedlings. 1. The activity of fructose 1,6-bisphosphatase (EC 3.1.3.11) in the fatty endosperm of castor bean (Ricinus communis) increases 25-fold during germination and then declines. The developmental pattern follows that of catalase, a marker enzyme for gluconeogenesis in this tissue. 2. The enzyme at its peak of development was partially purified, and its properties were studied. It has an optimal activity at neutral pH (7.0-8.0). The apparent Km value for fructose 1,6-bisphosphate is 3.8 X 10(-5) M. The activity is inhibited by AMP allosterically with an apparent Ki value of 2.2 X 10(-4) M. The enzyme hydrolyses fructose 1,6-bisphosphate and not ribulose 1,5-bisphosphate or sedoehptulose 1,7-bisphosphate. 3. Treatment of the partially purified enzyme with acid leads to an 80% decrease in activity. The remaining activity is insensitive to AMP and has optimal activity at pH 6.7 and a high apparent Km value (2.5 X 10(-4) M) for fructose 1.6-bisphosphate. Enzyme extracted from the tissue with water instead of buffer has a similar modification. The effect of acid explains the discrepancies between this report and previous ones on the properties of the enzyme in this tissue. 4. The storage tissues of various fatty seedlings all contain a 'neutral' fructose 1,6-bisphosphatase. The activities of the enzyme from some of the tissues are inhibited by AMP. 5. The properties of the enzyme in fatty seedlings and in green leaves are discussed in comparison with that in animal tissues."} {"id": "PMID:182125", "title": "Muscarinic cholinergic stimulation of phosphatidylinositol turnover in the longitudinal smooth muscle of guinea-pig ileum.", "content": "1. The metabolism of phosphatidylinositol and phosphatidate was investigated in fragments of longitudinal smooth muscle from guinea-pig ileum incubated with cholinergic and anticholinergic drugs. 2. Incorporation of Pi into these lipids was enhanced by acetylcholine and carbamoylcholine. 3. The receptor responsible for triggering this response was of the muscarinic type, since (a) the response was also produced by the muscarinic agonists acetyl-beta-methylcholine, carbamoyl-beta-methylcholine and pilocarpine, and (b) the response was prevented by atropine and prophylbenzilylcholine mustard, but not by tubocurarine. 4. Increased phosphatidylinositol labellin was clearly observed within 5 min in tissue treated with a high concentration of carbamoylcholine. 5. Halfmaximal stimulation of phosphatidylinositol labelling occurred at approx. 10 muM-muM-carbamoylcholine. 6. Incubation of muscle fragments with carbamoylcholine provoked a decrease in phosphatidylinositol concentration, as would be expected if phosphatidyl-inositol breakdown is the reaction controlled by agonists. 7. This information all appears consistent with the proposal that phosphatidylinositol breakdown may be a reaction intrinsic to the mechanisms of muscarinic cholinergic receptor systems.", "contents": "Muscarinic cholinergic stimulation of phosphatidylinositol turnover in the longitudinal smooth muscle of guinea-pig ileum. 1. The metabolism of phosphatidylinositol and phosphatidate was investigated in fragments of longitudinal smooth muscle from guinea-pig ileum incubated with cholinergic and anticholinergic drugs. 2. Incorporation of Pi into these lipids was enhanced by acetylcholine and carbamoylcholine. 3. The receptor responsible for triggering this response was of the muscarinic type, since (a) the response was also produced by the muscarinic agonists acetyl-beta-methylcholine, carbamoyl-beta-methylcholine and pilocarpine, and (b) the response was prevented by atropine and prophylbenzilylcholine mustard, but not by tubocurarine. 4. Increased phosphatidylinositol labellin was clearly observed within 5 min in tissue treated with a high concentration of carbamoylcholine. 5. Halfmaximal stimulation of phosphatidylinositol labelling occurred at approx. 10 muM-muM-carbamoylcholine. 6. Incubation of muscle fragments with carbamoylcholine provoked a decrease in phosphatidylinositol concentration, as would be expected if phosphatidyl-inositol breakdown is the reaction controlled by agonists. 7. This information all appears consistent with the proposal that phosphatidylinositol breakdown may be a reaction intrinsic to the mechanisms of muscarinic cholinergic receptor systems."} {"id": "PMID:182126", "title": "Effects of calcium ions and adenosine diphosphate on the activities of NAD+-linked isocitrate dehydrogenase from the radular muscles of the whelk and flight muscles of insects.", "content": "1. The activity of NAD+-linked isocitrate dehydrogenase from the radular muscle of the whelk is higher than those in many vertebrate muscles and only slightly lower than in the flight muscles of insects. The enzyme activity from the whelk (Buccinum undatum) is stable for several hours after homogenization of the radular muscle, whereas that from insect flight muscle is very unstable. Consequently, the enzyme from the whelk muscle is suitable for a systematic investigation of the effects of Ca2+ and ADP. 2. The sigmoid response of the enzyme activity to isocitrate concentration is markedly increased by raising the Ca2+ concentration from 0.001 to 10 muM, but it is decreased by ADP. The inhibitory effect of Ca2+ is most pronounced at pH7.1; it is not observed at pH 6.5. Similar effects are observed for the enzyme from the flight muscle of the locust (Schistocerca gregaria) and the water bug (Lethocerus cordofanus). The percentage activation by ADP of the enzyme from either the whelk or the insects is greater at 10 muM-Ca2+, and 50% of the maximum activation is obtained at 0.10 and 0.16 mM-ADP for the enzyme from whelk and locust respectively at this Ca2+ concentration. At 10 muM-Ca2+ in the absence of added ADP, the apparent Km for isocitrate is markedly higher than in other conditions. Ca2+ concentrations of 0.01, 0.1 and 0.2 muM cause 50% inhibition of maximum activity of the enzyme from the muscles of the whelk, locust and water bug respectively. 3. Recent work has indicated that mitochondria may play a complementary role to the sarcoplasmic reticulum in the control of the distribution of Ca2+ in muscle. The opposite effects of Ca2+ on the activities of isocitrate dehydrogenase and mitochondrial glycerol phosphate dehydrogenase from muscle tissue are consistent with the hypothesis that changes in the intracellular distribution of Ca2+ control the activities of these two enzymes in order to stimulate energy production for the contraction process in the muscle. Although both enzymes are mitochondrial, glycerol phosphate dehydrogenase resides on the outer surface of the inner membrane and responds to sarcoplasmic changes in Ca2+ concentration (i.e. an increase during contraction), whereas the isocitrate dehydrogenase resides in the matrix of the mitochondria and responds to intramitochondrial concentrations of Ca2+ (i.e. a decrease during contraction). It is suggested that changes in intramitochondrial Ca2+ concentrations are primarily responsible for regulation of the activity of NAD+-isocitrate dehydrogenase in order to control energy formation for the contractile process. However, when the muscle is at rest, changes in intramitochondrial concentrations of ADP may regulate energy formation for non-contractile processes.", "contents": "Effects of calcium ions and adenosine diphosphate on the activities of NAD+-linked isocitrate dehydrogenase from the radular muscles of the whelk and flight muscles of insects. 1. The activity of NAD+-linked isocitrate dehydrogenase from the radular muscle of the whelk is higher than those in many vertebrate muscles and only slightly lower than in the flight muscles of insects. The enzyme activity from the whelk (Buccinum undatum) is stable for several hours after homogenization of the radular muscle, whereas that from insect flight muscle is very unstable. Consequently, the enzyme from the whelk muscle is suitable for a systematic investigation of the effects of Ca2+ and ADP. 2. The sigmoid response of the enzyme activity to isocitrate concentration is markedly increased by raising the Ca2+ concentration from 0.001 to 10 muM, but it is decreased by ADP. The inhibitory effect of Ca2+ is most pronounced at pH7.1; it is not observed at pH 6.5. Similar effects are observed for the enzyme from the flight muscle of the locust (Schistocerca gregaria) and the water bug (Lethocerus cordofanus). The percentage activation by ADP of the enzyme from either the whelk or the insects is greater at 10 muM-Ca2+, and 50% of the maximum activation is obtained at 0.10 and 0.16 mM-ADP for the enzyme from whelk and locust respectively at this Ca2+ concentration. At 10 muM-Ca2+ in the absence of added ADP, the apparent Km for isocitrate is markedly higher than in other conditions. Ca2+ concentrations of 0.01, 0.1 and 0.2 muM cause 50% inhibition of maximum activity of the enzyme from the muscles of the whelk, locust and water bug respectively. 3. Recent work has indicated that mitochondria may play a complementary role to the sarcoplasmic reticulum in the control of the distribution of Ca2+ in muscle. The opposite effects of Ca2+ on the activities of isocitrate dehydrogenase and mitochondrial glycerol phosphate dehydrogenase from muscle tissue are consistent with the hypothesis that changes in the intracellular distribution of Ca2+ control the activities of these two enzymes in order to stimulate energy production for the contraction process in the muscle. Although both enzymes are mitochondrial, glycerol phosphate dehydrogenase resides on the outer surface of the inner membrane and responds to sarcoplasmic changes in Ca2+ concentration (i.e. an increase during contraction), whereas the isocitrate dehydrogenase resides in the matrix of the mitochondria and responds to intramitochondrial concentrations of Ca2+ (i.e. a decrease during contraction). It is suggested that changes in intramitochondrial Ca2+ concentrations are primarily responsible for regulation of the activity of NAD+-isocitrate dehydrogenase in order to control energy formation for the contractile process. However, when the muscle is at rest, changes in intramitochondrial concentrations of ADP may regulate energy formation for non-contractile processes."} {"id": "PMID:182127", "title": "Binding of Concanavalin A and its effect on the differentiation of Dictyostelium Discoideum.", "content": "Dictyostelium discoideum amoebae have two classes of binding sites for concanavalin A, one accessible to a competitive inhibitor of concanavalin A binding and one inaccessible. Uptake of concanavalin A occurs and is associated with a transfer from accessible to inaccessible binding sites. Low amounts of concanavalin A bound to cells produce a slight stimulation of differentiation, and this is associated with an increase in production of phosphodiesterase. Above a critical amount of concanavalin A bound, cell differentiation and phosphodiesterase production are inhibited. The relationship of concanavalin A-induced membrane changes to cell differentation is discussed.", "contents": "Binding of Concanavalin A and its effect on the differentiation of Dictyostelium Discoideum. Dictyostelium discoideum amoebae have two classes of binding sites for concanavalin A, one accessible to a competitive inhibitor of concanavalin A binding and one inaccessible. Uptake of concanavalin A occurs and is associated with a transfer from accessible to inaccessible binding sites. Low amounts of concanavalin A bound to cells produce a slight stimulation of differentiation, and this is associated with an increase in production of phosphodiesterase. Above a critical amount of concanavalin A bound, cell differentiation and phosphodiesterase production are inhibited. The relationship of concanavalin A-induced membrane changes to cell differentation is discussed."} {"id": "PMID:182128", "title": "Reactions involving superoxide and normal and unstable haemoglobins.", "content": "Superoxide ions (O2-) oxidized oxyhaemoglobin to methaemoglobin and reduced methaemoglobin to oxyhaemoglobin. The reactions of superoxide and H2O2 with oxyhaemoglobin or methaemoglobin and their inhibition by superoxide dismutase or catalase were used to detect the formation of superoxide or H2O2 on autoxidation of oxyhaemoglobin. The rate of autoxidation was decreased at about 35% in the presence of both enzymes. The copper-catalysed autoxidation of Hb (haemoglobin) was also shown to involve superoxide production. Superoxide was released on autoxidation of three unstable haemoglobins and isolated alpha and beta chains, at rates faster than with Hb A. Reactions of superoxide with Hb Christchurch and Hb Belfast were identical with those with Hb A, and occurred at the same rate. Hb Koln contrasted with the other haemoglobins in that the thiol groups of residue beta-93 as well as the haem groups reacted with superoxide. Haemichrome formation from methaemoglobin occurred very rapidly with Hb Christchurch and Hb Belfast, as well as the isolated chains, compared with Hb A. The process did not involve superoxide production or utilization. The relative importance of autoxidation and superoxide production compared with haemichrome formation in the haemolytic process associated with these abnormal haemoglobins and thalassaemia is considered.", "contents": "Reactions involving superoxide and normal and unstable haemoglobins. Superoxide ions (O2-) oxidized oxyhaemoglobin to methaemoglobin and reduced methaemoglobin to oxyhaemoglobin. The reactions of superoxide and H2O2 with oxyhaemoglobin or methaemoglobin and their inhibition by superoxide dismutase or catalase were used to detect the formation of superoxide or H2O2 on autoxidation of oxyhaemoglobin. The rate of autoxidation was decreased at about 35% in the presence of both enzymes. The copper-catalysed autoxidation of Hb (haemoglobin) was also shown to involve superoxide production. Superoxide was released on autoxidation of three unstable haemoglobins and isolated alpha and beta chains, at rates faster than with Hb A. Reactions of superoxide with Hb Christchurch and Hb Belfast were identical with those with Hb A, and occurred at the same rate. Hb Koln contrasted with the other haemoglobins in that the thiol groups of residue beta-93 as well as the haem groups reacted with superoxide. Haemichrome formation from methaemoglobin occurred very rapidly with Hb Christchurch and Hb Belfast, as well as the isolated chains, compared with Hb A. The process did not involve superoxide production or utilization. The relative importance of autoxidation and superoxide production compared with haemichrome formation in the haemolytic process associated with these abnormal haemoglobins and thalassaemia is considered."} {"id": "PMID:182129", "title": "The rate of reaction of superoxide radical ion with oxyhaemoglobin and methaemoglobin.", "content": "Superoxide radical ions (O2-) produced by the radiolytic reduction of oxygenated formate solutions and by the xanthine oxidase-catalysed oxidation of xanthine were shown to oxidize the haem groups in oxyhaemoglobin and reduce those in methaemoglobin as in reactions (1) and (2): (see articles) Reaction (1) is suppressed by reaction (8) when [O2-]exceeds 10 muM, but consumes all the O2- generated in oxyhaemoglobin solutions when [oxyhaemoglobin] greater than 160 muM and [O2-]less than 1 nM at pH 7. The yield of reaction (2) is also maximal in methaemoglobin solutions under similar conditions, but less than one haem group is reduced per O2- radical. From studies of (a) the yield of reactions (1) and (2) at variable [haemoglobin] and rates of production of O2-, (b) their suppression by superoxide dismutase, and (c) equilibria observed with mixtures of oxyhaemoglobin and methaemoglobin, it is shown that k1/k2=0.7 +/- 0.2 and k1 = (4 +/- 1) X 10(3) M-1-S-1 At pH7, and k1 and k2 decrease with increasing pH. Concentrations and rate constants are expressed in terms of haem-group concentrations. Concentrations of superoxide dismutase observed in normal erythrocytes are sufficient to suppress reactions (1) and (2), and hence prevent the formation of excessive methaemoglobin.", "contents": "The rate of reaction of superoxide radical ion with oxyhaemoglobin and methaemoglobin. Superoxide radical ions (O2-) produced by the radiolytic reduction of oxygenated formate solutions and by the xanthine oxidase-catalysed oxidation of xanthine were shown to oxidize the haem groups in oxyhaemoglobin and reduce those in methaemoglobin as in reactions (1) and (2): (see articles) Reaction (1) is suppressed by reaction (8) when [O2-]exceeds 10 muM, but consumes all the O2- generated in oxyhaemoglobin solutions when [oxyhaemoglobin] greater than 160 muM and [O2-]less than 1 nM at pH 7. The yield of reaction (2) is also maximal in methaemoglobin solutions under similar conditions, but less than one haem group is reduced per O2- radical. From studies of (a) the yield of reactions (1) and (2) at variable [haemoglobin] and rates of production of O2-, (b) their suppression by superoxide dismutase, and (c) equilibria observed with mixtures of oxyhaemoglobin and methaemoglobin, it is shown that k1/k2=0.7 +/- 0.2 and k1 = (4 +/- 1) X 10(3) M-1-S-1 At pH7, and k1 and k2 decrease with increasing pH. Concentrations and rate constants are expressed in terms of haem-group concentrations. Concentrations of superoxide dismutase observed in normal erythrocytes are sufficient to suppress reactions (1) and (2), and hence prevent the formation of excessive methaemoglobin."} {"id": "PMID:182130", "title": "Iodination of glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus.", "content": "The reaction of iodine with glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus was investigated. The active-site thiol group of the cysteine residue homologous with cysteine-149 in the pig muscle enzyme was protected by reaction with tetrathionate. The apoenzyme was readily inhibited by KI3 solution at pH8, but the coenzyme, NAD+, protected the enzyme against inhibition and decreased the extent of iodination. At pH 9.5, ready inhibition of both apo- and holo-enzyme was observed. Tryptic peptides containing residues iodinated at pH 8 were isolated and characterized. One of the most reactive residues in both holo- and apo-enzymes was a tyrosine homologous with tyrosine-46 in the pig muscle enzyme, and this residue was iodinated without loss of enzymic activity. Other reactive tyrosine residues in the apoenzyme were in positions homologous with residues 178, 273, 283 and 311 in the pig muscle enzyme, but they were not readily iodinated in the holoenzyme. Histidine residues in both holo- and apo-enzymes were iodinated at pH 8 in sequence positions homologous with residues 50, 162 and 190 in the pig muscle enzyme. The inhibition of the enzyme was not correlated with the iodination of a particular residue. The results are discussed in relation to a three-dimensional model based on the structure of the lobster muscle enzyme and demonstrate that conformational changes affecting the reactivity of several tyrosine residues most probably occur on binding of the coenzyme.", "contents": "Iodination of glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus. The reaction of iodine with glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus was investigated. The active-site thiol group of the cysteine residue homologous with cysteine-149 in the pig muscle enzyme was protected by reaction with tetrathionate. The apoenzyme was readily inhibited by KI3 solution at pH8, but the coenzyme, NAD+, protected the enzyme against inhibition and decreased the extent of iodination. At pH 9.5, ready inhibition of both apo- and holo-enzyme was observed. Tryptic peptides containing residues iodinated at pH 8 were isolated and characterized. One of the most reactive residues in both holo- and apo-enzymes was a tyrosine homologous with tyrosine-46 in the pig muscle enzyme, and this residue was iodinated without loss of enzymic activity. Other reactive tyrosine residues in the apoenzyme were in positions homologous with residues 178, 273, 283 and 311 in the pig muscle enzyme, but they were not readily iodinated in the holoenzyme. Histidine residues in both holo- and apo-enzymes were iodinated at pH 8 in sequence positions homologous with residues 50, 162 and 190 in the pig muscle enzyme. The inhibition of the enzyme was not correlated with the iodination of a particular residue. The results are discussed in relation to a three-dimensional model based on the structure of the lobster muscle enzyme and demonstrate that conformational changes affecting the reactivity of several tyrosine residues most probably occur on binding of the coenzyme."} {"id": "PMID:182131", "title": "Thymidine phosphotransferase and nucleotide phosphohydrolase of the fern Asplenium nidus. General properties and inhibition by adenosine 3':5'-cyclic monophosphate.", "content": "1. Extracts of several plant species contained nucleoside-AMP phosphotransferase activity. The ratio of activity with thymidine to that with uridine as nucleoside substrate was essentially constant, both between species and throughout plant development. Evidence is presented that the total thymidine-AMP phosphotransferase activity of the leaves of Asplenium nidus (bird's-nest fern) and of Helianthus tuberosus (Jerusalem artichoke) increases during maturation. 2. Thymidine-AMP phosphotransferase was purified 22-fold from a very rich source of this activity, extracts of A. nidus. 3. A broad specificity towards both nucleoside and nucleoside 5'-monophosphate substrates is displayed by this preparation, and the evidence suggests that all could be due to a single enzyme. 4. Nucleosides that act as substrates will also inhibit phosphotransfer to other nucleosides, with Ki values close to the corresponding Km values found when utilized as substrates. 5. Ca2+-activated ATP phosphohydrolase was separated from the phosphotransferase by differential complexing to Blue Dextran in the presence of urea, whereas an AMP phosphohydrolase activity was closely associated with thymidine-AMP phosphotransferase through all separation techniques used. 6. Metal ions did not activate either of the latter two activities, and 1,10-phenanthroline was found to inhibit the phosphotransferase. 7. Km values for AMP for the respective activities were 0.11 mM (thymidine phosphotransferase) and 0.20 mM (AMP phosphohydrolase) and for thymidine (phosphotransferase only) 0.88 mM. 8. 3':5'-Cyclic AMP was found to inhibit both phosphotransferase and AMP phosphohydrolase activities, with Ki values of 0.056 mM and 0.15 mM respectively. It is suggested that this inhibitor would be of value in revealing the existence of thymidine kinase in plant extracts with high thymidine phosphotransferase activity.", "contents": "Thymidine phosphotransferase and nucleotide phosphohydrolase of the fern Asplenium nidus. General properties and inhibition by adenosine 3':5'-cyclic monophosphate. 1. Extracts of several plant species contained nucleoside-AMP phosphotransferase activity. The ratio of activity with thymidine to that with uridine as nucleoside substrate was essentially constant, both between species and throughout plant development. Evidence is presented that the total thymidine-AMP phosphotransferase activity of the leaves of Asplenium nidus (bird's-nest fern) and of Helianthus tuberosus (Jerusalem artichoke) increases during maturation. 2. Thymidine-AMP phosphotransferase was purified 22-fold from a very rich source of this activity, extracts of A. nidus. 3. A broad specificity towards both nucleoside and nucleoside 5'-monophosphate substrates is displayed by this preparation, and the evidence suggests that all could be due to a single enzyme. 4. Nucleosides that act as substrates will also inhibit phosphotransfer to other nucleosides, with Ki values close to the corresponding Km values found when utilized as substrates. 5. Ca2+-activated ATP phosphohydrolase was separated from the phosphotransferase by differential complexing to Blue Dextran in the presence of urea, whereas an AMP phosphohydrolase activity was closely associated with thymidine-AMP phosphotransferase through all separation techniques used. 6. Metal ions did not activate either of the latter two activities, and 1,10-phenanthroline was found to inhibit the phosphotransferase. 7. Km values for AMP for the respective activities were 0.11 mM (thymidine phosphotransferase) and 0.20 mM (AMP phosphohydrolase) and for thymidine (phosphotransferase only) 0.88 mM. 8. 3':5'-Cyclic AMP was found to inhibit both phosphotransferase and AMP phosphohydrolase activities, with Ki values of 0.056 mM and 0.15 mM respectively. It is suggested that this inhibitor would be of value in revealing the existence of thymidine kinase in plant extracts with high thymidine phosphotransferase activity."} {"id": "PMID:182132", "title": "[Nitrotyrosyl]cytochrome c. Studies of the effect of iron binding, protein denaturants and oxidation-reduction potentials.", "content": "Static measurements of the reaction of ligand binding were done by conventional spectrophotometry. The ligand-binding reactions with nitrated cytochrome c were performed with imidazole, iminazole, CO and NO. The stoicheiometry was found to be 1:1, and the stability constants for the complexes formed between the nitrated cytochrome c and the ligands are: 2.58 X 10(4) M-1 (imidazole); 1.01 X 10(2) M-1 (iminazole); 3.6 X 10(4) M-1 (CO); 2.74 X 10(4) M-1 (NO). It was found that the electrometric potentials at pH 7.0 and 25degreesC of [aminotyrosyl]cytochrome c are E'o form II = 0.115 V and E'o form I = 0.260 V, where forms I and II are two species of protein co-existing in the protein solution. The isoelectric point for the oxidized form of [nitrotyrosyl]cytochrome c was 10.05, at 4degreesC.", "contents": "[Nitrotyrosyl]cytochrome c. Studies of the effect of iron binding, protein denaturants and oxidation-reduction potentials. Static measurements of the reaction of ligand binding were done by conventional spectrophotometry. The ligand-binding reactions with nitrated cytochrome c were performed with imidazole, iminazole, CO and NO. The stoicheiometry was found to be 1:1, and the stability constants for the complexes formed between the nitrated cytochrome c and the ligands are: 2.58 X 10(4) M-1 (imidazole); 1.01 X 10(2) M-1 (iminazole); 3.6 X 10(4) M-1 (CO); 2.74 X 10(4) M-1 (NO). It was found that the electrometric potentials at pH 7.0 and 25degreesC of [aminotyrosyl]cytochrome c are E'o form II = 0.115 V and E'o form I = 0.260 V, where forms I and II are two species of protein co-existing in the protein solution. The isoelectric point for the oxidized form of [nitrotyrosyl]cytochrome c was 10.05, at 4degreesC."} {"id": "PMID:182133", "title": "Purification of phosphodiesterase II from rat and guinea-pig intestinal mucosa.", "content": "Phosphodiesterase II from extracts of intestinal mucosa of rat and guinea pig was purified by chromatography on DEAE-cellulose, CM-cellulose and agarose. The rat enzyme was purified 350-550-fold, with recoveries ranging up to 46%. The best purification of the guinea-pig enzyme was 15-fold, and the recovery was only 2.6%, the large loss occurring during chromatography on DEAE-cellulose and agarose. The poor results with the guinea-pig enzyme reflect the difficulty in obtaining a truly soluble material. Repeated sonication of the crude guinea-pig preparations yielded material that was initially soluble but tended to re-aggregate quickly. Purification of the rat phosphodiesterase II increased its thermostability, the temperature of half-inactivation being increased from 54degrees to 60degreesC. Both enzymes had a Km value of 4 X 10(-5) M with thymidine 3'-(2,4-dinitrophenyl) phosphate as substrate and showed similar pH optima for activity. Both enzymes were inhibited slightly in 0.1 M-MgC12 or 2M-urea and much more strongly in 2M-(NH4)2SO4 or 6M-NaC1. The guinea-pig enzyme was usually inhibited more than the rat enzyme. The Arrhenius plots of the two enzymes differed slightly in slope, but both were biphasic, showing breaks between 30degrees and 40degreesC. It was concluded that the two enzymes were markedly similar in behaviour and that the differences found were related to the different degrees of purification attained by the procedures described.", "contents": "Purification of phosphodiesterase II from rat and guinea-pig intestinal mucosa. Phosphodiesterase II from extracts of intestinal mucosa of rat and guinea pig was purified by chromatography on DEAE-cellulose, CM-cellulose and agarose. The rat enzyme was purified 350-550-fold, with recoveries ranging up to 46%. The best purification of the guinea-pig enzyme was 15-fold, and the recovery was only 2.6%, the large loss occurring during chromatography on DEAE-cellulose and agarose. The poor results with the guinea-pig enzyme reflect the difficulty in obtaining a truly soluble material. Repeated sonication of the crude guinea-pig preparations yielded material that was initially soluble but tended to re-aggregate quickly. Purification of the rat phosphodiesterase II increased its thermostability, the temperature of half-inactivation being increased from 54degrees to 60degreesC. Both enzymes had a Km value of 4 X 10(-5) M with thymidine 3'-(2,4-dinitrophenyl) phosphate as substrate and showed similar pH optima for activity. Both enzymes were inhibited slightly in 0.1 M-MgC12 or 2M-urea and much more strongly in 2M-(NH4)2SO4 or 6M-NaC1. The guinea-pig enzyme was usually inhibited more than the rat enzyme. The Arrhenius plots of the two enzymes differed slightly in slope, but both were biphasic, showing breaks between 30degrees and 40degreesC. It was concluded that the two enzymes were markedly similar in behaviour and that the differences found were related to the different degrees of purification attained by the procedures described."} {"id": "PMID:182134", "title": "Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity.", "content": "1. Isoelectric focusing studies of human placental diamine oxidase showed the pI value of the active enzyme to be 6.5. This information was used in modifying the enzyme purification by incorporating column chromatography on DEAE-Sephadex with ionic strength and pH gradient elution and this, together with affinity chromatography on concanavalin A--Sepharose, gave a highly purified preparation, with a specific activity of 7.0 units/mg. 2. The enzyme gave the expected stoicheiometry with p-dimethylaminomethylbenzylamine as substrate (Keq. 2700) and also oxidized [8-arginine]vasopressin, [8-lysine]vasopressin, collagen and tropocollagen. Polyacrylamide gel slices showed identical migration of diamine-oxidizing and [8-lysine]vasopressin-oxidizing activity. 3. The molecular weight, determined by ultracentrifugation, sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, variable polyacrylamide-gel electrophoresis and Sephadex G-200 column chromatography, was estimated to be approx. 70000. 4. E.s.r. spectroscopy showed that copper and manganese were present in the purified enzyme. This result was confirmed by atomic absorption spectroscopy, which indicated a stoicheiometry for copper and manganese of approx. 1.0 and 1.2g-atom respectively/70000mol.wt. unit. 5. The e.s.r. spectral intensity did not decrease nor did the spectral line shape change when excess of p-dimethylaminomethylbenzylamine was added to the enzyme. 6. Addition of K13CN to the enzyme eliminated the copper e.s.r. signal without affecting the manganese signal. 7. The placental enzyme therefore appears to differ from other amine oxidases in terms of its metal cofactor requirement, molecular weight and substrate specificity, and possible roles in vivo for this enzyme are discussed.", "contents": "Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity. 1. Isoelectric focusing studies of human placental diamine oxidase showed the pI value of the active enzyme to be 6.5. This information was used in modifying the enzyme purification by incorporating column chromatography on DEAE-Sephadex with ionic strength and pH gradient elution and this, together with affinity chromatography on concanavalin A--Sepharose, gave a highly purified preparation, with a specific activity of 7.0 units/mg. 2. The enzyme gave the expected stoicheiometry with p-dimethylaminomethylbenzylamine as substrate (Keq. 2700) and also oxidized [8-arginine]vasopressin, [8-lysine]vasopressin, collagen and tropocollagen. Polyacrylamide gel slices showed identical migration of diamine-oxidizing and [8-lysine]vasopressin-oxidizing activity. 3. The molecular weight, determined by ultracentrifugation, sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, variable polyacrylamide-gel electrophoresis and Sephadex G-200 column chromatography, was estimated to be approx. 70000. 4. E.s.r. spectroscopy showed that copper and manganese were present in the purified enzyme. This result was confirmed by atomic absorption spectroscopy, which indicated a stoicheiometry for copper and manganese of approx. 1.0 and 1.2g-atom respectively/70000mol.wt. unit. 5. The e.s.r. spectral intensity did not decrease nor did the spectral line shape change when excess of p-dimethylaminomethylbenzylamine was added to the enzyme. 6. Addition of K13CN to the enzyme eliminated the copper e.s.r. signal without affecting the manganese signal. 7. The placental enzyme therefore appears to differ from other amine oxidases in terms of its metal cofactor requirement, molecular weight and substrate specificity, and possible roles in vivo for this enzyme are discussed."} {"id": "PMID:182135", "title": "Effects of arginine and some analogues of the partial adenosine triphosphate-adenosine diphosphate exchange reaction catalysed by arginine kinase. Evolutionary divergence in the mechanism of action of a monomer and a dimer arginine kinase.", "content": "1. Both the monomer arginine kinase from lobster muscle and the dimer arginine kinase from Holothuria forskali catalyse the ATP-ADP partial exchange reaction at rates equal to 3 and 0.6% of the normal rate of transphosphorylation respectively. The Mg2+-nucleotide complex is the substrate for this as it is for the kinase reaction. 2. Analogues of arginine inhibit the exchange reaction of the lobster enzyme but enhance that of the Holothuria enzyme. 3. With the lobster enzyme NO3- has no effect on the exchange reaction alone and inhibit only slightly the apparent enhancement of the exchange reaction produced by the addition of arginine. This is compatible with previous findings for this enzyme that formation of the anion-stabilized dead-end complex, enzyme-arginine-MgADP-NO3-, does not occur to any marked degree. 4. About 80% of the ADP-ATP exchange reaction of the lobster enzyme remains after inhibition with iodoacetamide. This is further decreased to 65% by the addition of L-arginine, indicating that this substrate does bind to the thiolmodified enzyme. 5. It is concluded that the partial exchange reaction is a genuine phenomenon not mediated by trace amounts of arginine. From the effects of arginine and related compounds it would appear that during the normal kinase reaction the partial ATP-ADP exchange reaction is suppressed in the lobster enzyme but enhanced in the Holothuria enzyme. This reflects a remarkable evolutionary divergence of two homologous enzymes.", "contents": "Effects of arginine and some analogues of the partial adenosine triphosphate-adenosine diphosphate exchange reaction catalysed by arginine kinase. Evolutionary divergence in the mechanism of action of a monomer and a dimer arginine kinase. 1. Both the monomer arginine kinase from lobster muscle and the dimer arginine kinase from Holothuria forskali catalyse the ATP-ADP partial exchange reaction at rates equal to 3 and 0.6% of the normal rate of transphosphorylation respectively. The Mg2+-nucleotide complex is the substrate for this as it is for the kinase reaction. 2. Analogues of arginine inhibit the exchange reaction of the lobster enzyme but enhance that of the Holothuria enzyme. 3. With the lobster enzyme NO3- has no effect on the exchange reaction alone and inhibit only slightly the apparent enhancement of the exchange reaction produced by the addition of arginine. This is compatible with previous findings for this enzyme that formation of the anion-stabilized dead-end complex, enzyme-arginine-MgADP-NO3-, does not occur to any marked degree. 4. About 80% of the ADP-ATP exchange reaction of the lobster enzyme remains after inhibition with iodoacetamide. This is further decreased to 65% by the addition of L-arginine, indicating that this substrate does bind to the thiolmodified enzyme. 5. It is concluded that the partial exchange reaction is a genuine phenomenon not mediated by trace amounts of arginine. From the effects of arginine and related compounds it would appear that during the normal kinase reaction the partial ATP-ADP exchange reaction is suppressed in the lobster enzyme but enhanced in the Holothuria enzyme. This reflects a remarkable evolutionary divergence of two homologous enzymes."} {"id": "PMID:182136", "title": "Ascorbic acid, metal ions and the superoxide radical.", "content": "1. No evidence could be found for production of the superoxide radical, O2-, during autoxidation of ascorbic acid at alkaline pH values. Indeed, ascorbate may be important in protection against O2- genat-d in vivo. 2. Oxidation of ascorbate at pH 10.2 was stimulated by metal ions. Stimulation by Fe2+ was abolished by superoxide dismutase, probably because of generation of O2-- during reduction of O2 by Fe2+, followed by reaction of O2-- with ascorbate. EDTA changed the mechanism of Fe2+-stimulated ascorbate oxidation. 3. Stimulation of ascorbate oxidation by Cu2+ was also decreased by superoxide dismutase, but this appears to be an artifact, since apoenzyme or bovine serum albumin showed similar effects.", "contents": "Ascorbic acid, metal ions and the superoxide radical. 1. No evidence could be found for production of the superoxide radical, O2-, during autoxidation of ascorbic acid at alkaline pH values. Indeed, ascorbate may be important in protection against O2- genat-d in vivo. 2. Oxidation of ascorbate at pH 10.2 was stimulated by metal ions. Stimulation by Fe2+ was abolished by superoxide dismutase, probably because of generation of O2-- during reduction of O2 by Fe2+, followed by reaction of O2-- with ascorbate. EDTA changed the mechanism of Fe2+-stimulated ascorbate oxidation. 3. Stimulation of ascorbate oxidation by Cu2+ was also decreased by superoxide dismutase, but this appears to be an artifact, since apoenzyme or bovine serum albumin showed similar effects."} {"id": "PMID:182137", "title": "Stimulation of prolactin synthesis and of adenosine 3':5'-cyclic phosphate formation by prostaglandins and thyroliberin in cultured rat pituitary cells.", "content": "1. The effects of prostaglandins E2 and F2alpha on prolactin synthesis were examined in a clonal strain of rat pituitary tumour cells, and compared with those of thyroliberin. 2. The prostaglandins and thyroliberin gave a dose-related and time-dependent stimulation of prolactin synthesis. The maximal effects (about twofold increases) were observed after 54h of treatment with 25nM-prostaglandin E2 and 2.5nM-prostaglandin F2alpha. A similar stimulation of prolactin synthesis was observed after 250nM-thyroliberin. The combined treatment with prostaglandins and thyroliberin did not increase prolactin synthesis over and above that obtained with each compound alone. 3. After removal of prostaglandins E2 and F2alpha there was a complete reversal of prolactin synthesis to pre-stimulation values 18h later (t1/2less than or equal to 9h). The rapid reversible effect of prostaglandins was in contrast with that of thyroliberin, where prolactin synthesis returned to control values with a t1/2 of about 42 h. 4. Prostaglandin E2 (5mum) and thyroliberin (5mum) increased cellular concentrations of cyclic AMP eight- and four-fold respectively. Maximal effects were observed after 2-5min of incubation. The increases in cyclic AMP were biphasic; normal values were obtained 60 min after the start of incubation with prostaglandin E2 or thyroliberin. 5. The dose/response curve showed that prostaglandin E2 caused maximal increase of cyclic AMP at 50nM. Concentrations of prostagland in E2 that caused half-maximal stimulation of cyclic AMP accumulation and of prolactin synthesis were 4 and 5nM respectively. 6. Combined treatment with prostaglandin E2 and thyroliberin in concentrations that separately caused maximal cyclic AMP increases did not result in a further increase in this cyclic nucleotide. 7. These results are consistent with a role of cyclic AMP in mediating the effects or prostaglandins and thyroliberin on prolactin synthesis. However, if cyclic AMP is involved as a common intracellular mediator of prolactin synthesis, it cannot alone explain all the effects of prostaglandins and thyroliberin in this cell system.", "contents": "Stimulation of prolactin synthesis and of adenosine 3':5'-cyclic phosphate formation by prostaglandins and thyroliberin in cultured rat pituitary cells. 1. The effects of prostaglandins E2 and F2alpha on prolactin synthesis were examined in a clonal strain of rat pituitary tumour cells, and compared with those of thyroliberin. 2. The prostaglandins and thyroliberin gave a dose-related and time-dependent stimulation of prolactin synthesis. The maximal effects (about twofold increases) were observed after 54h of treatment with 25nM-prostaglandin E2 and 2.5nM-prostaglandin F2alpha. A similar stimulation of prolactin synthesis was observed after 250nM-thyroliberin. The combined treatment with prostaglandins and thyroliberin did not increase prolactin synthesis over and above that obtained with each compound alone. 3. After removal of prostaglandins E2 and F2alpha there was a complete reversal of prolactin synthesis to pre-stimulation values 18h later (t1/2less than or equal to 9h). The rapid reversible effect of prostaglandins was in contrast with that of thyroliberin, where prolactin synthesis returned to control values with a t1/2 of about 42 h. 4. Prostaglandin E2 (5mum) and thyroliberin (5mum) increased cellular concentrations of cyclic AMP eight- and four-fold respectively. Maximal effects were observed after 2-5min of incubation. The increases in cyclic AMP were biphasic; normal values were obtained 60 min after the start of incubation with prostaglandin E2 or thyroliberin. 5. The dose/response curve showed that prostaglandin E2 caused maximal increase of cyclic AMP at 50nM. Concentrations of prostagland in E2 that caused half-maximal stimulation of cyclic AMP accumulation and of prolactin synthesis were 4 and 5nM respectively. 6. Combined treatment with prostaglandin E2 and thyroliberin in concentrations that separately caused maximal cyclic AMP increases did not result in a further increase in this cyclic nucleotide. 7. These results are consistent with a role of cyclic AMP in mediating the effects or prostaglandins and thyroliberin on prolactin synthesis. However, if cyclic AMP is involved as a common intracellular mediator of prolactin synthesis, it cannot alone explain all the effects of prostaglandins and thyroliberin in this cell system."} {"id": "PMID:182138", "title": "Regulation of carbohydrate metabolism in lymphoid tissue. Nature of the endogenous substrates and their contribution to the respiratory fuel of the sliced rat spleen in vitro.", "content": "1. Tissue glycogen contributes, maximally, only 10% of the respiratory fuel of the rat spleen slice in the absence of an added carbon source, and makes no significant contribution when glucose (3mM) is added. 2. The reserves of fatty acid in the form of triglyceride (35.5mumol of fatty acid/g dry wt. of tissue) fall by approx. 25% after incubation of spleen slices with or without added glucose for 2h, and , on this basis, account for 32% of the oxidative fuel. 3. In contrast, the total oxidative contribution of fatty acid reserves to the respiratory fuel, determined on the basis of inhibiton of respiration by 2-bromostearate, is 42-52%. This range includes tissue from both starved and well-fed animals and is not significantly altered by the presence of added glycose (3mM). 4. Large quantities of NH3 (31-35mumol//h per g dry wt. of tissue) are produced by spleen slices incubated in the absence of added substrates, and this value is suppressed by approx. 50% on incubation with glucose (3mM). Adenine nucleotide breakdown can account for only 17% of the total ammonia produced. 5. Individual free amino acid concentrations in spleen were determined, both in vivo and in slices before and after 60 min of incubation. Although the total free amino acid pool size increases by 45% during incubation, owing to protein breakdown, the tissue concentrations of aspartate, glutamate, glutamine and alanine do not increase. It is suggested that these amino acids areoxidized in a net sense to CO2 and water with the liberation of free NH3 via transamination reactions, glutaminase, the purine nucleotide cycle and the tricarboxylic acid cycle. 6. It is concluded that the normal endogenous metabolism of sliced rat spleen (43-52% due to lipids, 30% due to amino acids and 10% due to glycogen) is modified by added glycose only to the extent that glycogen oxidation and 50% of the contribtion made by ino acids are suppressed; endogenous lipid metabolism is unaffected.", "contents": "Regulation of carbohydrate metabolism in lymphoid tissue. Nature of the endogenous substrates and their contribution to the respiratory fuel of the sliced rat spleen in vitro. 1. Tissue glycogen contributes, maximally, only 10% of the respiratory fuel of the rat spleen slice in the absence of an added carbon source, and makes no significant contribution when glucose (3mM) is added. 2. The reserves of fatty acid in the form of triglyceride (35.5mumol of fatty acid/g dry wt. of tissue) fall by approx. 25% after incubation of spleen slices with or without added glucose for 2h, and , on this basis, account for 32% of the oxidative fuel. 3. In contrast, the total oxidative contribution of fatty acid reserves to the respiratory fuel, determined on the basis of inhibiton of respiration by 2-bromostearate, is 42-52%. This range includes tissue from both starved and well-fed animals and is not significantly altered by the presence of added glycose (3mM). 4. Large quantities of NH3 (31-35mumol//h per g dry wt. of tissue) are produced by spleen slices incubated in the absence of added substrates, and this value is suppressed by approx. 50% on incubation with glucose (3mM). Adenine nucleotide breakdown can account for only 17% of the total ammonia produced. 5. Individual free amino acid concentrations in spleen were determined, both in vivo and in slices before and after 60 min of incubation. Although the total free amino acid pool size increases by 45% during incubation, owing to protein breakdown, the tissue concentrations of aspartate, glutamate, glutamine and alanine do not increase. It is suggested that these amino acids areoxidized in a net sense to CO2 and water with the liberation of free NH3 via transamination reactions, glutaminase, the purine nucleotide cycle and the tricarboxylic acid cycle. 6. It is concluded that the normal endogenous metabolism of sliced rat spleen (43-52% due to lipids, 30% due to amino acids and 10% due to glycogen) is modified by added glycose only to the extent that glycogen oxidation and 50% of the contribtion made by ino acids are suppressed; endogenous lipid metabolism is unaffected."} {"id": "PMID:182139", "title": "Nuclear components responsible for the retention of steroid--receptor complexes, especially from the standpoint of the specifcity of hormonal responses.", "content": "1. By covalently linking nuclear components from hormone-sensitive cells to Sepharose 2B, it is possible to investigate the interaction between nuclear components and cytoplasmic receptor-steroid complexes by affinity chromatography. 2. Many factors are implicated in the specifity of nuclear-cytoplasmic interactions, including the nature of the nuclear components, the presence of the cytoplasmic receptor protein and the provision of the appropriate steroid ligand. 3. Two distinct sets of binding sites are present in nuclear extracts immobilized to Sepharose 2B, namely a small number of specific high-affinity sites and a larger number of non-specific low affinity-sites. 4. Considerable evidence supports the importance of the high-affinity binding sites in the manifestation of hormonal specificity in different tissues. Although the study has centred largely on androgenresponsive systems, the findings are germane to cytoplasmic-nuclear interactions in general. 5. The high-affinity or acceptor sites in nuclear extracts reside in the basic but non-histone protein fraction. 6. Hormonal specificity is seemingly maintained by both the cytoplasmic and nuclear components, and the results are discussed in the context of the mechanism of action of steroid hormones.", "contents": "Nuclear components responsible for the retention of steroid--receptor complexes, especially from the standpoint of the specifcity of hormonal responses. 1. By covalently linking nuclear components from hormone-sensitive cells to Sepharose 2B, it is possible to investigate the interaction between nuclear components and cytoplasmic receptor-steroid complexes by affinity chromatography. 2. Many factors are implicated in the specifity of nuclear-cytoplasmic interactions, including the nature of the nuclear components, the presence of the cytoplasmic receptor protein and the provision of the appropriate steroid ligand. 3. Two distinct sets of binding sites are present in nuclear extracts immobilized to Sepharose 2B, namely a small number of specific high-affinity sites and a larger number of non-specific low affinity-sites. 4. Considerable evidence supports the importance of the high-affinity binding sites in the manifestation of hormonal specificity in different tissues. Although the study has centred largely on androgenresponsive systems, the findings are germane to cytoplasmic-nuclear interactions in general. 5. The high-affinity or acceptor sites in nuclear extracts reside in the basic but non-histone protein fraction. 6. Hormonal specificity is seemingly maintained by both the cytoplasmic and nuclear components, and the results are discussed in the context of the mechanism of action of steroid hormones."} {"id": "PMID:182140", "title": "Effect of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 on translocation.", "content": "1. The effect of elongation factor 2 (EF 2) and of adenosine diphosphate-ribosylated elongation factor 2 (ADP-ribosyl-EF 2) on the shift of endogenous peptidyl-tRNA from the A to the P site of rat liver ribosomes (measured by the peptidyl-puromycin reaction) and on the release of deacylated tRNA (measured by aminoacylation) was investigated. 2. Limiting amounts of EF2, pre-bound or added to ribosomes, catalyse the shift of peptidyl-tRNA in the presence of GPT; when the enzyme is added in substrate amounts GMP-P(CH2)P [guanosine (beta, gamma-methylene)triphosphate] can partially replace GTP. ADP-ribosyl-EF 2 has no effect on the shift of peptidyl-tRNA when present in catalytic amounts, but becomes almost as effective as EF 2 when added in substrate amounts together with GTP; GMP-P(CH2)P cannot replace GTP. 3. The release of deacylated tRNA is induced only by substrate amounts of added EF 2 and also occurs in the absence of guanine nucleotides. In this reaction ADP-ribosyl-EF 2 is only 25% as effective as EF 2 in the absence of added nucleotide, but becomes 60-80% as effective in the presence of GTP or GMP-P(CH2)P. 4. The results obtained on protein-synthesizing systems are consistent with the hypothesis that ADP-ribosyl-EF 2 can operate a single round of translocation followed by binding of aminoacyl-tRNA and peptide-bond formation. 5. From the data obtained with the native enzyme it is concluded that the two moments of translocation require different conditions of interaction of EF 2 with ribosomes; it is suggested that the shift of peptidyl-tRNA is catalysed by EF 2 pre-bound to ribosomes, and that the release of tRNA is induced by a second molecule of interacting EF 2. The hydrolysis of GTP would be required for the release of pre-bound EF 2 from ribosomes. 5. The inhibition of the utilization of limiting amounts of EF 2 on ADP-ribosylation is very likely the consequence of a concomitant decrease in the rate of association and dissociation of the enzyme from ribosomes.", "contents": "Effect of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 on translocation. 1. The effect of elongation factor 2 (EF 2) and of adenosine diphosphate-ribosylated elongation factor 2 (ADP-ribosyl-EF 2) on the shift of endogenous peptidyl-tRNA from the A to the P site of rat liver ribosomes (measured by the peptidyl-puromycin reaction) and on the release of deacylated tRNA (measured by aminoacylation) was investigated. 2. Limiting amounts of EF2, pre-bound or added to ribosomes, catalyse the shift of peptidyl-tRNA in the presence of GPT; when the enzyme is added in substrate amounts GMP-P(CH2)P [guanosine (beta, gamma-methylene)triphosphate] can partially replace GTP. ADP-ribosyl-EF 2 has no effect on the shift of peptidyl-tRNA when present in catalytic amounts, but becomes almost as effective as EF 2 when added in substrate amounts together with GTP; GMP-P(CH2)P cannot replace GTP. 3. The release of deacylated tRNA is induced only by substrate amounts of added EF 2 and also occurs in the absence of guanine nucleotides. In this reaction ADP-ribosyl-EF 2 is only 25% as effective as EF 2 in the absence of added nucleotide, but becomes 60-80% as effective in the presence of GTP or GMP-P(CH2)P. 4. The results obtained on protein-synthesizing systems are consistent with the hypothesis that ADP-ribosyl-EF 2 can operate a single round of translocation followed by binding of aminoacyl-tRNA and peptide-bond formation. 5. From the data obtained with the native enzyme it is concluded that the two moments of translocation require different conditions of interaction of EF 2 with ribosomes; it is suggested that the shift of peptidyl-tRNA is catalysed by EF 2 pre-bound to ribosomes, and that the release of tRNA is induced by a second molecule of interacting EF 2. The hydrolysis of GTP would be required for the release of pre-bound EF 2 from ribosomes. 5. The inhibition of the utilization of limiting amounts of EF 2 on ADP-ribosylation is very likely the consequence of a concomitant decrease in the rate of association and dissociation of the enzyme from ribosomes."} {"id": "PMID:182141", "title": "The biochemistry of fatty liver and kidney syndrome. Biotin-mediated restoration of hepatic gluconeogenesis in vitro and its relationship to pyruvate carboxylase activity.", "content": "Liver slices from chicks affected by the fatty liver and kidney syndrome display an extremely low extent of hepatic gluconeogenesis which is associated with decreased activities of certain rate-limiting gluconeogenic enzymes. Pyruvate carboxylase activity is particularly severely affected, being less than 4% of control values. Incubation of affected slices in a biotin-containing nutrient medium restores both gluconeogenesis and pyruvate carboxylase actiivity (the latter to approx. 35% of the control valve). Activities of the other enzymes studied were not greatly affected by this treatment. Restoration of gluconeogenesis did not occur if biotin was excluded from the nutrient medium, nor was it prevented by protein-synthesis inhibitors. It is concluded that the syndrome involves the lack of available biotin in the liver rather than suppression of apocarboxylase synthesis.", "contents": "The biochemistry of fatty liver and kidney syndrome. Biotin-mediated restoration of hepatic gluconeogenesis in vitro and its relationship to pyruvate carboxylase activity. Liver slices from chicks affected by the fatty liver and kidney syndrome display an extremely low extent of hepatic gluconeogenesis which is associated with decreased activities of certain rate-limiting gluconeogenic enzymes. Pyruvate carboxylase activity is particularly severely affected, being less than 4% of control values. Incubation of affected slices in a biotin-containing nutrient medium restores both gluconeogenesis and pyruvate carboxylase actiivity (the latter to approx. 35% of the control valve). Activities of the other enzymes studied were not greatly affected by this treatment. Restoration of gluconeogenesis did not occur if biotin was excluded from the nutrient medium, nor was it prevented by protein-synthesis inhibitors. It is concluded that the syndrome involves the lack of available biotin in the liver rather than suppression of apocarboxylase synthesis."} {"id": "PMID:182143", "title": "The purification and biological properties of pancreatic big glucagon.", "content": "1. Big glucagon was present in extracts of ox, dog, rat and turkey pancreas, representing 10-15% of the glucagon immunoreactivity, and was shown to be of islet origin by its presence in extracts of isolated pigeon islets. 2. Big glucagon was homogeneous by immunoassay after polyacrylamide-gel electrophoresis and was more electronegative than little glucagon. 3. Big glucagon was purified from bovine pancreas, and its apparent molecular weight was estimated by gel filtration as 8200+/-9%. 4. Limited tryptic proteolysis of the molecule produced an immunoreactive component slightly smaller than little glucagon. 5. Linear dilution curves were obtained with mammalian big glucagons by using both enteroglucagon cross-reacting and 'little-glucagon-carboxyl-end-specific' antisera. 6. The half-times for the disappearance of the immunoreactivity of big and little glucagon that had been injected into the rat circulation were 6.9 and 3.2min respectively. 7. Big glucagon was approximately one-sixth as effective as little glucagon in displacing radioactive little glucagon from its liver membrane receptor. 8. Big glucagon was equipotent on a molar basis with little glucagon in the stimulation of the mouse islet adenylate cyclase, an indicator of insulinogenic activity. 9. On a molar basis, big glucagon inhibited basal liver adenylate cyclase activity to the same extent that little glucagon stimulated the enzyme. 10. Big glucagon was without effect on blood glucose concentration in the rat in doses up to 5mug/kg. 11. Big glucagon was equipotent, on a molar basis, with little glucagon in stimulating lipolysis in isolated chicken fat-cells.", "contents": "The purification and biological properties of pancreatic big glucagon. 1. Big glucagon was present in extracts of ox, dog, rat and turkey pancreas, representing 10-15% of the glucagon immunoreactivity, and was shown to be of islet origin by its presence in extracts of isolated pigeon islets. 2. Big glucagon was homogeneous by immunoassay after polyacrylamide-gel electrophoresis and was more electronegative than little glucagon. 3. Big glucagon was purified from bovine pancreas, and its apparent molecular weight was estimated by gel filtration as 8200+/-9%. 4. Limited tryptic proteolysis of the molecule produced an immunoreactive component slightly smaller than little glucagon. 5. Linear dilution curves were obtained with mammalian big glucagons by using both enteroglucagon cross-reacting and 'little-glucagon-carboxyl-end-specific' antisera. 6. The half-times for the disappearance of the immunoreactivity of big and little glucagon that had been injected into the rat circulation were 6.9 and 3.2min respectively. 7. Big glucagon was approximately one-sixth as effective as little glucagon in displacing radioactive little glucagon from its liver membrane receptor. 8. Big glucagon was equipotent on a molar basis with little glucagon in the stimulation of the mouse islet adenylate cyclase, an indicator of insulinogenic activity. 9. On a molar basis, big glucagon inhibited basal liver adenylate cyclase activity to the same extent that little glucagon stimulated the enzyme. 10. Big glucagon was without effect on blood glucose concentration in the rat in doses up to 5mug/kg. 11. Big glucagon was equipotent, on a molar basis, with little glucagon in stimulating lipolysis in isolated chicken fat-cells."} {"id": "PMID:182142", "title": "Calcium uptake by subcellular fractions of pancreatic islets. Effects of nucleotides and theophylline.", "content": "Uptake of 45Ca2+ by a microsomal fraction isolated pancreatic islets of non-inbred ob/ob mice was studied. ATP strongly stimulated 45Ca2+ uptake, the maximum effect being obtained with 2mM-ATP. GTP and CTP at this concentration did not increase the uptake. Scatchard analysis revealed at least two types of uptake mechanisms in the presence of 2mM-ATP; the apparent association constants were 1.1 x 10(5)m(-1) and less than 2.5 x 10(2)m(-1). In contradistinction to an unaffected low-affinity uptake, the high-affinity uptake was drastically decreased on ommission of ATP. The ATP-dependent and high-affinity uptake was half-saturated at about 10-20mum-Ca(2+) and was inhibited by 10 or 100mum cyclic AMP, 10mum cyclic GMP, 10 mum cyclic GMP, or 5mm-theophylline. 45ca2+ uptake in the absence of ATP was not affected by 100mum-cyclic AMP. In view of its sensitivity to ATP and cyclic nucleotides, the high-affinity Ca2+-uptake mechaniam may play a role in stimulus-secretion coupling in the beta-cells by regulating the cytosolic concentration of Ca2+.", "contents": "Calcium uptake by subcellular fractions of pancreatic islets. Effects of nucleotides and theophylline. Uptake of 45Ca2+ by a microsomal fraction isolated pancreatic islets of non-inbred ob/ob mice was studied. ATP strongly stimulated 45Ca2+ uptake, the maximum effect being obtained with 2mM-ATP. GTP and CTP at this concentration did not increase the uptake. Scatchard analysis revealed at least two types of uptake mechanisms in the presence of 2mM-ATP; the apparent association constants were 1.1 x 10(5)m(-1) and less than 2.5 x 10(2)m(-1). In contradistinction to an unaffected low-affinity uptake, the high-affinity uptake was drastically decreased on ommission of ATP. The ATP-dependent and high-affinity uptake was half-saturated at about 10-20mum-Ca(2+) and was inhibited by 10 or 100mum cyclic AMP, 10mum cyclic GMP, 10 mum cyclic GMP, or 5mm-theophylline. 45ca2+ uptake in the absence of ATP was not affected by 100mum-cyclic AMP. In view of its sensitivity to ATP and cyclic nucleotides, the high-affinity Ca2+-uptake mechaniam may play a role in stimulus-secretion coupling in the beta-cells by regulating the cytosolic concentration of Ca2+."} {"id": "PMID:182144", "title": "Phospholipid composition of the plasma membrane of the green alga, Hydrodictyon africanum.", "content": "A plasma-membrane fraction was isolated from the alga Hydrodictyon africanum by micro-dissection and its phospholipid components were analysed. Phosphatidylcholine was the major phospholipid of the preparation. Both phosphatidylserine and diphosphatidylglycerol were enriched in the fraction compared with the whole cell, but the relative amount of phosphatidylglycerol present was less than that in the whole cell. Phosphatidylinositol was absent from the plasma-membrane preparation.", "contents": "Phospholipid composition of the plasma membrane of the green alga, Hydrodictyon africanum. A plasma-membrane fraction was isolated from the alga Hydrodictyon africanum by micro-dissection and its phospholipid components were analysed. Phosphatidylcholine was the major phospholipid of the preparation. Both phosphatidylserine and diphosphatidylglycerol were enriched in the fraction compared with the whole cell, but the relative amount of phosphatidylglycerol present was less than that in the whole cell. Phosphatidylinositol was absent from the plasma-membrane preparation."} {"id": "PMID:182145", "title": "The subcellular loclization and properties of the ferrochelatase of etiolated barley.", "content": "The etioplast fraction prepared from dark-grown barley contained the enzyme ferrochelatase. A mitochondrial fraction prepared from the same dark-grown tissue also contained ferrochelatase. After density-gradient centrifugation an etioplast band was collected that was free from detectable mitochondrial marker enzymes and yet retained ferrochelatase activity. A membrane band that was enriched in mitochondria also contained ferrochelatase. The ferrochelatase in these two bands had different pH optima, but appeared very similar in their porphyrin specificity and their inhibition by metalloporphyrins.", "contents": "The subcellular loclization and properties of the ferrochelatase of etiolated barley. The etioplast fraction prepared from dark-grown barley contained the enzyme ferrochelatase. A mitochondrial fraction prepared from the same dark-grown tissue also contained ferrochelatase. After density-gradient centrifugation an etioplast band was collected that was free from detectable mitochondrial marker enzymes and yet retained ferrochelatase activity. A membrane band that was enriched in mitochondria also contained ferrochelatase. The ferrochelatase in these two bands had different pH optima, but appeared very similar in their porphyrin specificity and their inhibition by metalloporphyrins."} {"id": "PMID:182146", "title": "Nuclear binding of progesterone in chick oviduct. Multiple binding sites in vivo and transcriptional response.", "content": "1. Varied doses of labelled or unlabelled progesterone were injected into immature chicks which had previously been stimulated with oestrogen. The concentrations of nuclear bound [3H]progesterone were correlated with the effects of the hormone on endogenous RNA polymerase I and II activities in isolated oviduct nuclei. 2. The extent of nuclear localization of [3H]progesterone in oviduct (a progesterone target tissue) was shown to be much greater than in lung (non-target tissue). The conccentration of bivalent cations in solvents used in the nuclei isolations has a marked effect on the amount of bound hormone in the nuclei. 3. Evidence for the existence of several classes of binding sites for progesterone in the oviduct nuclei is given. These classes represent about 1000) 10000 and 100000 molecules of the hormone per cell nucleus and are saturated by injecting approx. 10, 100 and 1000 mug of progesterone respectively. 4. When saturation of the first (highest affinity) class of nuclear sites occurs, a marked inhibition in RNA polymerase II (but not RNA polymerase I) activity was observed. When the second class of sites was saturated, alterations in both RNA polymerase I and II activities were observed. Binding to the third class of nuclear binding sites was not accompained by further changes in polymerase activity. It is suggested that the first two classes of nuclear binding sites may represent functional sites for progesterone action in the chick oviduct.", "contents": "Nuclear binding of progesterone in chick oviduct. Multiple binding sites in vivo and transcriptional response. 1. Varied doses of labelled or unlabelled progesterone were injected into immature chicks which had previously been stimulated with oestrogen. The concentrations of nuclear bound [3H]progesterone were correlated with the effects of the hormone on endogenous RNA polymerase I and II activities in isolated oviduct nuclei. 2. The extent of nuclear localization of [3H]progesterone in oviduct (a progesterone target tissue) was shown to be much greater than in lung (non-target tissue). The conccentration of bivalent cations in solvents used in the nuclei isolations has a marked effect on the amount of bound hormone in the nuclei. 3. Evidence for the existence of several classes of binding sites for progesterone in the oviduct nuclei is given. These classes represent about 1000) 10000 and 100000 molecules of the hormone per cell nucleus and are saturated by injecting approx. 10, 100 and 1000 mug of progesterone respectively. 4. When saturation of the first (highest affinity) class of nuclear sites occurs, a marked inhibition in RNA polymerase II (but not RNA polymerase I) activity was observed. When the second class of sites was saturated, alterations in both RNA polymerase I and II activities were observed. Binding to the third class of nuclear binding sites was not accompained by further changes in polymerase activity. It is suggested that the first two classes of nuclear binding sites may represent functional sites for progesterone action in the chick oviduct."} {"id": "PMID:182147", "title": "Nuclear binding of progesterone in hen oviduct. Binding to multiple sites in vitro.", "content": "Steroid hormones, including progesterone, are known to bind with high affinity (Kd approximately 1x10(-10)M) to receptor proteins once they enter target cells. This complex (the progesterone-receptor) then undergoes a temperature-and/or salt-dependent activation which allows it to migrate to the cell nucleus and to bind to the deoxyribonucleoproteins. The present studies demonstrate that binding the hormone-receptor complex in vitro to isolated nuclei from the oviducts of laying hens required the same conditions as do other studies of bbinding in vitro reported previously, e.g. the hormone must be complexed to intact and activated receptor. The assay of the nuclear binding by using multiple concentrations of progesterone receptor reveals the presence of more than one class of binding site in the oviduct nuclei. The affinity of each of these classes of binding sites range from Kd approximately 1x10(-9)-1x10(-8)M. Assays using free steroid (not complexed with receptor) show no binding to these sites. The binding to each of the classes of sites, displays a differential stability to increasing ionic concentrations, suggesting primarily an ionic-type interaction for all classes. Only the highest-affinity class of binding site is capable of binding progesterone receptor under physioligical-saline conditions. This class represent 6000-10000 sites per cell nucleus and resembles the sites detected in vivo (Spelsberg, 1976, Biochem. J. 156, 391-398) which cause maximal transcriptional response when saturated with the progesterone receptor. The multiple binding sites for the progesterone receptor either are not present or are found in limited numbers in the nuclei of non-target organs. Differences in extent of binding to the nuclear material between a target tissue (oviduct) and other tissues (spleen or erythrocyte) are markedly dependent on the ionic conditions, and are probably due to binding to different classes of sites in the nuclei.", "contents": "Nuclear binding of progesterone in hen oviduct. Binding to multiple sites in vitro. Steroid hormones, including progesterone, are known to bind with high affinity (Kd approximately 1x10(-10)M) to receptor proteins once they enter target cells. This complex (the progesterone-receptor) then undergoes a temperature-and/or salt-dependent activation which allows it to migrate to the cell nucleus and to bind to the deoxyribonucleoproteins. The present studies demonstrate that binding the hormone-receptor complex in vitro to isolated nuclei from the oviducts of laying hens required the same conditions as do other studies of bbinding in vitro reported previously, e.g. the hormone must be complexed to intact and activated receptor. The assay of the nuclear binding by using multiple concentrations of progesterone receptor reveals the presence of more than one class of binding site in the oviduct nuclei. The affinity of each of these classes of binding sites range from Kd approximately 1x10(-9)-1x10(-8)M. Assays using free steroid (not complexed with receptor) show no binding to these sites. The binding to each of the classes of sites, displays a differential stability to increasing ionic concentrations, suggesting primarily an ionic-type interaction for all classes. Only the highest-affinity class of binding site is capable of binding progesterone receptor under physioligical-saline conditions. This class represent 6000-10000 sites per cell nucleus and resembles the sites detected in vivo (Spelsberg, 1976, Biochem. J. 156, 391-398) which cause maximal transcriptional response when saturated with the progesterone receptor. The multiple binding sites for the progesterone receptor either are not present or are found in limited numbers in the nuclei of non-target organs. Differences in extent of binding to the nuclear material between a target tissue (oviduct) and other tissues (spleen or erythrocyte) are markedly dependent on the ionic conditions, and are probably due to binding to different classes of sites in the nuclei."} {"id": "PMID:182148", "title": "Nuclear binding of progesterone in hen oviduct. Role of acidic chromatin proteins in high-affinity binding.", "content": "The multiple classes of binding sites for the progesterone-receptor complex in hen oviduct muclei were found to be of chromatin origin. The highest-affinity, and presumably most physiologically important class, is localized in oviduct chromatin and contains approx. 6000-10000 sites per nucleus. None of these sites is detected in spleen chromatin. Two new techniques were used for assaying rapidly the binding of steroid-receptor complexes to soluble deoxyribonucleoproteins in vito. The extent of high-affinity binding by the nucleo-acidic protein fraction from spleen chromatin is as great as that by the nucleo-acidic protein from oviduct chromatin. Consequently the tissue-specific nuclear binding of the progesterone receptor is found not to be a consequence of the absence of the nuclear binding sites (acceptors) from chromatin of non-target tissue (spleen), but rather a result of complete masking of these sites. In the target-tissue (oviduct) chromatin, approx. 70% of the high-affinity acceptor sites are also masked. Acidic proteins, and not histones, appear to be responsible for the masking of these acceptor sites. In addition, acidic proteins represent (or at least are an essential part of) these high-affinity sites in the oviduct nucleus. Pure DNA displays a few high-and many low-affinity binding sites. In support of previous work with immature chicks, the acidic protein fraction of the nucleo-acidic results thus support the hypotheis that protein complexed with DNA, and not DNA alone, represent the high-affinity binding sites for the steroid-receptor complexes in nuclear chromatin. The lower-affinity classes of binding sites may represent DNA and/or other nuclear components.", "contents": "Nuclear binding of progesterone in hen oviduct. Role of acidic chromatin proteins in high-affinity binding. The multiple classes of binding sites for the progesterone-receptor complex in hen oviduct muclei were found to be of chromatin origin. The highest-affinity, and presumably most physiologically important class, is localized in oviduct chromatin and contains approx. 6000-10000 sites per nucleus. None of these sites is detected in spleen chromatin. Two new techniques were used for assaying rapidly the binding of steroid-receptor complexes to soluble deoxyribonucleoproteins in vito. The extent of high-affinity binding by the nucleo-acidic protein fraction from spleen chromatin is as great as that by the nucleo-acidic protein from oviduct chromatin. Consequently the tissue-specific nuclear binding of the progesterone receptor is found not to be a consequence of the absence of the nuclear binding sites (acceptors) from chromatin of non-target tissue (spleen), but rather a result of complete masking of these sites. In the target-tissue (oviduct) chromatin, approx. 70% of the high-affinity acceptor sites are also masked. Acidic proteins, and not histones, appear to be responsible for the masking of these acceptor sites. In addition, acidic proteins represent (or at least are an essential part of) these high-affinity sites in the oviduct nucleus. Pure DNA displays a few high-and many low-affinity binding sites. In support of previous work with immature chicks, the acidic protein fraction of the nucleo-acidic results thus support the hypotheis that protein complexed with DNA, and not DNA alone, represent the high-affinity binding sites for the steroid-receptor complexes in nuclear chromatin. The lower-affinity classes of binding sites may represent DNA and/or other nuclear components."} {"id": "PMID:182149", "title": "Role of ubiquinone in the mitochondrial generation of hydrogen peroxide.", "content": "Antimycin-inhibited bovine heart submitochondrial particles generate O2- and H2O2 with succinate as electron donor. H2O2 generation involves the action of the mitochondrial superoxide dismutase, in accordance with the McCord & Fridovich [(1969) j. biol. Chem. 244, 6049-6055] reaction mechanism. Removal of ubiquinone by acetone treatment decreases the ability of mitochondrial preparations to generate O2- and H2O2, whereas supplementation of the depleted membranes with ubiquinone enhances the peroxide-generating activity in the reconstituted membranes. Addition of superoxide dismutase to ubiquinone-reconstituted membranes is essential in order to obtain maximal rates of H2O2 generation since the acetone treatment of the membranes apparently inactivates (or removes) the mitochondrial superoxide dismutase. Parallel measurements of H2O2 production, succinate dehydrogenase and succinate-cytochrome c reductase activities show that peroxide generation by ubiquinone-supplemented membranes is a monotonous function of the reducible ubiquinone content, whereas the other two measured activities reach saturation at relatively low concentrations of reducible quinone. Alkaline treatment of submitochondrial particles causes a significant decrease in succinate dehydrogenase activity and succinate-dependent H2O2 production, which contrasts with the increase of peroxide production by the same particles with NADH as electron donor. Solubilized succinate dehydrogenase generates H2O2 at a much lower rate than the parent submitochondrial particles. It is postulated that ubisemiquinone (and ubiquinol) are chiefly responsible for the succinate-dependent peroxide production by the mitochondrial inner membrane.", "contents": "Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Antimycin-inhibited bovine heart submitochondrial particles generate O2- and H2O2 with succinate as electron donor. H2O2 generation involves the action of the mitochondrial superoxide dismutase, in accordance with the McCord & Fridovich [(1969) j. biol. Chem. 244, 6049-6055] reaction mechanism. Removal of ubiquinone by acetone treatment decreases the ability of mitochondrial preparations to generate O2- and H2O2, whereas supplementation of the depleted membranes with ubiquinone enhances the peroxide-generating activity in the reconstituted membranes. Addition of superoxide dismutase to ubiquinone-reconstituted membranes is essential in order to obtain maximal rates of H2O2 generation since the acetone treatment of the membranes apparently inactivates (or removes) the mitochondrial superoxide dismutase. Parallel measurements of H2O2 production, succinate dehydrogenase and succinate-cytochrome c reductase activities show that peroxide generation by ubiquinone-supplemented membranes is a monotonous function of the reducible ubiquinone content, whereas the other two measured activities reach saturation at relatively low concentrations of reducible quinone. Alkaline treatment of submitochondrial particles causes a significant decrease in succinate dehydrogenase activity and succinate-dependent H2O2 production, which contrasts with the increase of peroxide production by the same particles with NADH as electron donor. Solubilized succinate dehydrogenase generates H2O2 at a much lower rate than the parent submitochondrial particles. It is postulated that ubisemiquinone (and ubiquinol) are chiefly responsible for the succinate-dependent peroxide production by the mitochondrial inner membrane."} {"id": "PMID:182150", "title": "Long-term effects of a high glucose concentration on cyclic nucleotide phosphodiesterase activity in mouse pancreatic islets maintained in tissue culture.", "content": "It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin.", "contents": "Long-term effects of a high glucose concentration on cyclic nucleotide phosphodiesterase activity in mouse pancreatic islets maintained in tissue culture. It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin."} {"id": "PMID:182151", "title": "The existence of a glyconeogenic pathway in rat skin.", "content": "The existence of a glyconeogenic pathway in rat skin has been demonstrated by measurement of three of the key glyconeogenic enzymes, fructose 1,6-bisphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, and by studies on the incorporation in vitro of carbon from pyruvate and alanine into skin glycogen.", "contents": "The existence of a glyconeogenic pathway in rat skin. The existence of a glyconeogenic pathway in rat skin has been demonstrated by measurement of three of the key glyconeogenic enzymes, fructose 1,6-bisphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, and by studies on the incorporation in vitro of carbon from pyruvate and alanine into skin glycogen."} {"id": "PMID:182152", "title": "Energy-conserving reactions in phosphorylating electron-transport particles from Nitrobacter winogradskyi. Activation of nitrite oxidation by the electrical component of the protonmotive force.", "content": "1. In electron-transport particles (ET particles) prepared from Nitrobacter winogradskyi, the uncoupling agent carbonyl cyanide phenylhydrazone increased the rate of NADH oxidation but decreased the rate of oxidation of NO2-. Its effectiveness in stimulating NADH oxidation closely paralleled its effectiveness in inhibiting NO2- oxidation. 2. In the presence of ADP and phosphate the oxidation of NADH was stimulated, whereas the oxidation of NO2- was inhibited. In the presence of excess of Pi the concentration dependence with respect to ADP was the same for acceleration of NADH oxidation and inhibition of NO2- oxidation. 3. Oligomycin inhibited NADH oxidation and stimulated the oxidation of NO2-. The concentration of oligomycin required to produce half-maximal effect in both systems was the same. 4. The apparent Km for NO2- was not affected by ADP together with Pi, by uncoupling agent or by oligomycin. 5. With NADH as substrate, classical respiratory control was observed. With NO2- as substrate the respiratory-control ratio was less than unity. 6. A reversible uptake of H+ accompanied the oxidation of NO2- by ET particles. 7. In the presence of NH4Cl or cyclohexylamine hydrochloride, H+ uptake was abolished and increased rates of NO2- oxidation were observed. When valinomycin was present in the reaction medium, low concentrations of NH4Cl inhibited NO2- oxidation. 8. Pretreatment of ET particles with oligomycin enhanced the stimulation of NO2- oxidation induced by NH4Cl or by cyclohexylamine hydrochloride. Pretreatment with the uncoupler carbonyl cyanide phenylhydrazone prevented these stimulations. 9. In the presence of dianemycin together with K+, the uptake of H+ was abolished and the rate of NO2- oxidation was increased. In contrast, in the presence of valinomycin together with K+, the uptake of H+ was increased, and the rate of NO2- oxidation decreased. 10. Sodium tetraphenylboron was found to be an inhibitor of NO2- oxidation, but caused a stimulation of NADH oxidation which was dependent on the presence of NH4Cl or cyclohexylamine hydrochloride. 11. It is concluded that the enhanced rate of NO2- oxidation observed in the absence of energy-dissipating processes clearly relates to some state before the involvement of adenine nucleotides, and it is suggested that the oxidation of NO2- generates a protonmotive force, the electrical component of which controls the rate of NO2- oxidation.", "contents": "Energy-conserving reactions in phosphorylating electron-transport particles from Nitrobacter winogradskyi. Activation of nitrite oxidation by the electrical component of the protonmotive force. 1. In electron-transport particles (ET particles) prepared from Nitrobacter winogradskyi, the uncoupling agent carbonyl cyanide phenylhydrazone increased the rate of NADH oxidation but decreased the rate of oxidation of NO2-. Its effectiveness in stimulating NADH oxidation closely paralleled its effectiveness in inhibiting NO2- oxidation. 2. In the presence of ADP and phosphate the oxidation of NADH was stimulated, whereas the oxidation of NO2- was inhibited. In the presence of excess of Pi the concentration dependence with respect to ADP was the same for acceleration of NADH oxidation and inhibition of NO2- oxidation. 3. Oligomycin inhibited NADH oxidation and stimulated the oxidation of NO2-. The concentration of oligomycin required to produce half-maximal effect in both systems was the same. 4. The apparent Km for NO2- was not affected by ADP together with Pi, by uncoupling agent or by oligomycin. 5. With NADH as substrate, classical respiratory control was observed. With NO2- as substrate the respiratory-control ratio was less than unity. 6. A reversible uptake of H+ accompanied the oxidation of NO2- by ET particles. 7. In the presence of NH4Cl or cyclohexylamine hydrochloride, H+ uptake was abolished and increased rates of NO2- oxidation were observed. When valinomycin was present in the reaction medium, low concentrations of NH4Cl inhibited NO2- oxidation. 8. Pretreatment of ET particles with oligomycin enhanced the stimulation of NO2- oxidation induced by NH4Cl or by cyclohexylamine hydrochloride. Pretreatment with the uncoupler carbonyl cyanide phenylhydrazone prevented these stimulations. 9. In the presence of dianemycin together with K+, the uptake of H+ was abolished and the rate of NO2- oxidation was increased. In contrast, in the presence of valinomycin together with K+, the uptake of H+ was increased, and the rate of NO2- oxidation decreased. 10. Sodium tetraphenylboron was found to be an inhibitor of NO2- oxidation, but caused a stimulation of NADH oxidation which was dependent on the presence of NH4Cl or cyclohexylamine hydrochloride. 11. It is concluded that the enhanced rate of NO2- oxidation observed in the absence of energy-dissipating processes clearly relates to some state before the involvement of adenine nucleotides, and it is suggested that the oxidation of NO2- generates a protonmotive force, the electrical component of which controls the rate of NO2- oxidation."} {"id": "PMID:182153", "title": "Reduction of cytochromes by nitrite in electron-transport particles from Nitrobacter winogradskyi: proposal of a mechanism for H+ translocation.", "content": "1. A novel component in the respiratory chain of Nitrobacter winogradskyi was identified. This component absorbs maximally at 552.5 nm when in its reduced form, has an Eo' (pH7.0) value of-110mV and undergoes reduction by a mechanism involving the transfer of a single electron. 2. Degrees of reduction of cytochromes c and a1 in electron-transport (ET) particles were monitored during the course of NO2- oxidation, and the effects of ADP together with Pi, oligomycin and of carbonyl cyanide phenylhydrazone were determined. 3. The influences of ionophorous antibiotics, NH4Cl and cyclohexylamine hydrochloride on the reductions of cytochromes c and a1 by NO2- indicate that the flow of reducing equivalents from cytochrome a1 (+350mV) to cytochrome c (+270mV) is facilitated by deltapsi, the electrical component of the protonmotive force. 4. Cytochromes c and a1 in ET particles are reduced by the non-physiological reductant KBH4 in a manner similar to that observed with the physiological reductant NO2-. 5. To account both for the observed cytochrome reductions and for the translocation of H+ ions which accompanies NO2- oxidation, a mechanism is proposed which involves the transfer of a hydride equivalent (H+ plus 2e) inward across the membrane of the ET particle in response to deltapsi.", "contents": "Reduction of cytochromes by nitrite in electron-transport particles from Nitrobacter winogradskyi: proposal of a mechanism for H+ translocation. 1. A novel component in the respiratory chain of Nitrobacter winogradskyi was identified. This component absorbs maximally at 552.5 nm when in its reduced form, has an Eo' (pH7.0) value of-110mV and undergoes reduction by a mechanism involving the transfer of a single electron. 2. Degrees of reduction of cytochromes c and a1 in electron-transport (ET) particles were monitored during the course of NO2- oxidation, and the effects of ADP together with Pi, oligomycin and of carbonyl cyanide phenylhydrazone were determined. 3. The influences of ionophorous antibiotics, NH4Cl and cyclohexylamine hydrochloride on the reductions of cytochromes c and a1 by NO2- indicate that the flow of reducing equivalents from cytochrome a1 (+350mV) to cytochrome c (+270mV) is facilitated by deltapsi, the electrical component of the protonmotive force. 4. Cytochromes c and a1 in ET particles are reduced by the non-physiological reductant KBH4 in a manner similar to that observed with the physiological reductant NO2-. 5. To account both for the observed cytochrome reductions and for the translocation of H+ ions which accompanies NO2- oxidation, a mechanism is proposed which involves the transfer of a hydride equivalent (H+ plus 2e) inward across the membrane of the ET particle in response to deltapsi."} {"id": "PMID:182154", "title": "Regulation of phosphatidylcholine synthesis in rat liver endoplasmic reticulum.", "content": "The biosynthesis of phosphatidylcholine in rat liver microsomal preparations catalysed by CDP-choline-1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) was inhibited by a combination of ATP and CoA or ATP and pantetheine. ATP alone at high concentrations (20 mM) inhibits phosphatidylcholine formation to the extent of 70%. In the presence of 0.1 mM-CoA, ATP (2 mM) inhibits to the extent of 80% and in the presence of 1 mM-pantetheine to the extent of 90%. ADP and other nucleotide triphosphates in combination with either CoA or pantetheine are only 10-30% as effective in inhibiting phosphatidylcholine synthesis. AMP(CH2)PP [adenosine 5'-(alphabeta-methylene)triphosphate] together with CoA inhibits to the extent of 59% and with pantetheine by 48%. AMP-P(CH2)P [adenosine 5'-(betagamma-methylene)triphosphate] together with either CoA or pantetheine had no significant effect on phosphatidylcholine formation. Other closely related derivatives of pantothenic acid were without effect either alone or in the presence of ATP, as were thiol compounds such as cysteine, homocysteine, cysteamine, dithiothreitol and glutathione. Several mechanisms by which this inhibition might take place were ruled out and it is concluded that ATP together with either CoA or pantetheine interacts reversibly with phosphatidylcholine synthetase to cause temporarily the inhibition of phosphatidylcholine formation.", "contents": "Regulation of phosphatidylcholine synthesis in rat liver endoplasmic reticulum. The biosynthesis of phosphatidylcholine in rat liver microsomal preparations catalysed by CDP-choline-1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) was inhibited by a combination of ATP and CoA or ATP and pantetheine. ATP alone at high concentrations (20 mM) inhibits phosphatidylcholine formation to the extent of 70%. In the presence of 0.1 mM-CoA, ATP (2 mM) inhibits to the extent of 80% and in the presence of 1 mM-pantetheine to the extent of 90%. ADP and other nucleotide triphosphates in combination with either CoA or pantetheine are only 10-30% as effective in inhibiting phosphatidylcholine synthesis. AMP(CH2)PP [adenosine 5'-(alphabeta-methylene)triphosphate] together with CoA inhibits to the extent of 59% and with pantetheine by 48%. AMP-P(CH2)P [adenosine 5'-(betagamma-methylene)triphosphate] together with either CoA or pantetheine had no significant effect on phosphatidylcholine formation. Other closely related derivatives of pantothenic acid were without effect either alone or in the presence of ATP, as were thiol compounds such as cysteine, homocysteine, cysteamine, dithiothreitol and glutathione. Several mechanisms by which this inhibition might take place were ruled out and it is concluded that ATP together with either CoA or pantetheine interacts reversibly with phosphatidylcholine synthetase to cause temporarily the inhibition of phosphatidylcholine formation."} {"id": "PMID:182155", "title": "The stimulus-secretion coupling of glucose-induced insulin release. Does glycolysis control calcium transport in the B-cell?", "content": "1. The metabolism of glucose and the exchangeable Ca2+ pool were measured in rat pancreatic islets, in order to assess the possible significance of glycolysis in the process of glucose-induced insulin release. 2. At high glucose concentration (16.7 mM), glucose was metabolized at the following rate (pmol of glucose residue/h per islet +/- S.E.M.): 131 +/- 11 for glucose uptake, 129+/-8 for glucose utilization, as judged by the conversion of [5-3H]glucose into 3H2O,60+/-2 for lactate output and 25+/-2 for glucose oxidation. 3. The secretory pattern usually correlated with the metabolic data. For instance, the ability of different sugars (glucose, mannose, fructose, galactose, D-glyceraldehyde) to stimulate lactate output closely paralleled their relative insulinotropic capacity. A disparity between metabolic and secretory responses was, however, encountered in the presence of dibutyryl cyclic AMP and theophylline. 4. Despite this contrasting behaviour, the size of the Ca2+- exchangeable pool (net uptake of 45Ca2+) was invariably proportional to the rate of lactate output under all experimental conditions examined. It is concluded that glycolysis usually exerts a tight control on the rate constant for Ca2+ transport across the B-cell membrane.", "contents": "The stimulus-secretion coupling of glucose-induced insulin release. Does glycolysis control calcium transport in the B-cell? 1. The metabolism of glucose and the exchangeable Ca2+ pool were measured in rat pancreatic islets, in order to assess the possible significance of glycolysis in the process of glucose-induced insulin release. 2. At high glucose concentration (16.7 mM), glucose was metabolized at the following rate (pmol of glucose residue/h per islet +/- S.E.M.): 131 +/- 11 for glucose uptake, 129+/-8 for glucose utilization, as judged by the conversion of [5-3H]glucose into 3H2O,60+/-2 for lactate output and 25+/-2 for glucose oxidation. 3. The secretory pattern usually correlated with the metabolic data. For instance, the ability of different sugars (glucose, mannose, fructose, galactose, D-glyceraldehyde) to stimulate lactate output closely paralleled their relative insulinotropic capacity. A disparity between metabolic and secretory responses was, however, encountered in the presence of dibutyryl cyclic AMP and theophylline. 4. Despite this contrasting behaviour, the size of the Ca2+- exchangeable pool (net uptake of 45Ca2+) was invariably proportional to the rate of lactate output under all experimental conditions examined. It is concluded that glycolysis usually exerts a tight control on the rate constant for Ca2+ transport across the B-cell membrane."} {"id": "PMID:182156", "title": "Activity and androgenic control of glycolytic enzymes in the epididymis and epididymal spermatozoa of the rat.", "content": "1. Procedures were developed for the extraction and assay of glycolytic enzymes from the epididymis and epididymal spermatozoa of the rat. 2. The epididymis was separated into four segments for analysis. When rendered free of spermatozoa by efferent duct ligation, regional differences in enzyme activity were apparent. Phosphofructokinase, glycerol phosphate dehydrogenase and glucose 6-phosphate dehydrogenase were more active in the proximal regions of the epididymis, whereas hexokinase, lactate dehydrogenase and phosphorylase were more active in the distal segment. These enzymes were less active in the epididymis of castrated animals and less difference was apparent between the proximal and distal segments. However, the corpus epididymidis from castrated rats had lower activities of almost all enzymes compared with other epididymal segments. 3. Spermatozoa required sonication to obtain satisfactory enzyme release. Glycolytic enzymes were more active in spermatozoa than in epididymal tissue, being more than 10 times as active in the case of hexokinase, phosphoglycerate kinase and phosphoglycerate mutase. 4. The specific activities of a number of enzymes in the epididymis were dependent on the androgen status of the animal. These included hexokinase, phosphofructokinase, aldolase, glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, glycerol phosphate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and phosphorylase. 5. The caput and cauda epididymidis differed in the extent to which enzyme activities changed in response to an altered androgen status. The most notable examples were hexokinase, phosphofructokinase, aldolase, phosphoglycerate kinase, 6-phosphogluconate dehydrogenase and phosphorylase.", "contents": "Activity and androgenic control of glycolytic enzymes in the epididymis and epididymal spermatozoa of the rat. 1. Procedures were developed for the extraction and assay of glycolytic enzymes from the epididymis and epididymal spermatozoa of the rat. 2. The epididymis was separated into four segments for analysis. When rendered free of spermatozoa by efferent duct ligation, regional differences in enzyme activity were apparent. Phosphofructokinase, glycerol phosphate dehydrogenase and glucose 6-phosphate dehydrogenase were more active in the proximal regions of the epididymis, whereas hexokinase, lactate dehydrogenase and phosphorylase were more active in the distal segment. These enzymes were less active in the epididymis of castrated animals and less difference was apparent between the proximal and distal segments. However, the corpus epididymidis from castrated rats had lower activities of almost all enzymes compared with other epididymal segments. 3. Spermatozoa required sonication to obtain satisfactory enzyme release. Glycolytic enzymes were more active in spermatozoa than in epididymal tissue, being more than 10 times as active in the case of hexokinase, phosphoglycerate kinase and phosphoglycerate mutase. 4. The specific activities of a number of enzymes in the epididymis were dependent on the androgen status of the animal. These included hexokinase, phosphofructokinase, aldolase, glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, glycerol phosphate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and phosphorylase. 5. The caput and cauda epididymidis differed in the extent to which enzyme activities changed in response to an altered androgen status. The most notable examples were hexokinase, phosphofructokinase, aldolase, phosphoglycerate kinase, 6-phosphogluconate dehydrogenase and phosphorylase."} {"id": "PMID:182157", "title": "Selective control of the degradation of normal and aberrant proteins in Reuber H35 hepatoma cells.", "content": "1. Rates of degradation of normal and abnormal protein were measured in hepatoma cells after labelling first for 16h with [14C]leucine plus L-arginine and then for 3h with [3H]-leucine plus the arginine analogue, L-canavanine. 2. Over the first 2h of the degradation period, canavanine-containing proteins were degraded at approximately 5 times the average degradation rate of normal proteins. 3. Degradation of normal proteins was inhibited by about 30% by insulin, cycloheximide, puromycin, leupeptin, antipain and foetal calf serum, whereas these agents had a negligible effect on the breakdown of canavanine-containing proteins. 4. Other compounds inhibited degradation of both classes of protein to equal extents. 5. Combination experiments showed no additional inhibitory effects on the degradation of normal proteins over degradation measured in the presence of a single selective inhibitor. 6. In contrast with the results with a 16 h labelling period, the degradation of normal proteins labelled for only 3 h was not inhibited by insulin. 7. These results are explained by a model with two distinct pathways of protein turnover. The first of these pathways involves the formation of autophagic vacuoles and would be completely inhibited by each of the selective inhibitors. Normal and canavanine-containing proteins would be catabolized by this pathway at equal rates. We propose that degradation by a second pathway is not regulated by the agents tested, but by the inherent stability of each protein.", "contents": "Selective control of the degradation of normal and aberrant proteins in Reuber H35 hepatoma cells. 1. Rates of degradation of normal and abnormal protein were measured in hepatoma cells after labelling first for 16h with [14C]leucine plus L-arginine and then for 3h with [3H]-leucine plus the arginine analogue, L-canavanine. 2. Over the first 2h of the degradation period, canavanine-containing proteins were degraded at approximately 5 times the average degradation rate of normal proteins. 3. Degradation of normal proteins was inhibited by about 30% by insulin, cycloheximide, puromycin, leupeptin, antipain and foetal calf serum, whereas these agents had a negligible effect on the breakdown of canavanine-containing proteins. 4. Other compounds inhibited degradation of both classes of protein to equal extents. 5. Combination experiments showed no additional inhibitory effects on the degradation of normal proteins over degradation measured in the presence of a single selective inhibitor. 6. In contrast with the results with a 16 h labelling period, the degradation of normal proteins labelled for only 3 h was not inhibited by insulin. 7. These results are explained by a model with two distinct pathways of protein turnover. The first of these pathways involves the formation of autophagic vacuoles and would be completely inhibited by each of the selective inhibitors. Normal and canavanine-containing proteins would be catabolized by this pathway at equal rates. We propose that degradation by a second pathway is not regulated by the agents tested, but by the inherent stability of each protein."} {"id": "PMID:182158", "title": "Effect of haematocrit value and pO2 on the redox state and metabolism of the perfused liver.", "content": "1. The haematocrit value and pO2 of blood perfusing the isolated liver were varied. Provided O2 content of the blood was not rate-limiting, O2 consumption was related to haemotocrit value rather than O2 saturation or pO2. 2. Hypoxia caused the blood-glucose concentration and ketogenesis to increase and the output of very-low-density (d less than 1.006) lipoproteins to decrease. 3. A decrease in pO2 caused an increase in both the (lactate)/(pyruvate) and (3-hydroxybutyrate)/(acetoacetate) and a decrease in (ATP)/(ADP) ratios, independently of O2 consumption. 4. The more reduced redox state was associated with a shift in the balance between the oxidation and esterification of free fatty acids in favour of oxidation. 5. Acetoacetate may be an important hydrogen acceptor during hypoxia of the liver.", "contents": "Effect of haematocrit value and pO2 on the redox state and metabolism of the perfused liver. 1. The haematocrit value and pO2 of blood perfusing the isolated liver were varied. Provided O2 content of the blood was not rate-limiting, O2 consumption was related to haemotocrit value rather than O2 saturation or pO2. 2. Hypoxia caused the blood-glucose concentration and ketogenesis to increase and the output of very-low-density (d less than 1.006) lipoproteins to decrease. 3. A decrease in pO2 caused an increase in both the (lactate)/(pyruvate) and (3-hydroxybutyrate)/(acetoacetate) and a decrease in (ATP)/(ADP) ratios, independently of O2 consumption. 4. The more reduced redox state was associated with a shift in the balance between the oxidation and esterification of free fatty acids in favour of oxidation. 5. Acetoacetate may be an important hydrogen acceptor during hypoxia of the liver."} {"id": "PMID:182180", "title": "Solid phase radioimmunoassay of apolipoprotein B (apo B) in normal human plasma.", "content": "A solid phase radioimmunoassay (RIA) has been developed for apolipoprotein B (apoB), a major constituent of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in man. Antisera were prepared against apoB in goats and rabbits, coupled to bromoacetyle cellulose, and the complex was incubated with [125I] LDL. The RIA was based on the displacement of [ 1252]-LDL by unknown samples, as compared with unlabeled LDL standards, using a logit transformation to calculate results. The RIA was found to be satisfactory in terms of precision, sensitivity, reproducibility and specificity. Control subjects had mean apoB levels of 94 mg/100 ml in whole fasting plasma, of which 3.6 mg/100 ml plasma were in the VLDL, while 86 mg/100 ml plasma were in the LDL. Both the triglyceride and apoB content of VLDL, and the cholesterol and apoB content of LDL were positively correlated. It is concluded that the solid phase radioimmunoassay described in the present report provides a rapid and relatively simple means of quantitating apoB in normal human plasma.", "contents": "Solid phase radioimmunoassay of apolipoprotein B (apo B) in normal human plasma. A solid phase radioimmunoassay (RIA) has been developed for apolipoprotein B (apoB), a major constituent of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in man. Antisera were prepared against apoB in goats and rabbits, coupled to bromoacetyle cellulose, and the complex was incubated with [125I] LDL. The RIA was based on the displacement of [ 1252]-LDL by unknown samples, as compared with unlabeled LDL standards, using a logit transformation to calculate results. The RIA was found to be satisfactory in terms of precision, sensitivity, reproducibility and specificity. Control subjects had mean apoB levels of 94 mg/100 ml in whole fasting plasma, of which 3.6 mg/100 ml plasma were in the VLDL, while 86 mg/100 ml plasma were in the LDL. Both the triglyceride and apoB content of VLDL, and the cholesterol and apoB content of LDL were positively correlated. It is concluded that the solid phase radioimmunoassay described in the present report provides a rapid and relatively simple means of quantitating apoB in normal human plasma."} {"id": "PMID:182181", "title": "Results of colestipol therapy in Type II hyperlipoproteinemia.", "content": "Twenty-five patinets with well defined Type ii hyperlipoproteinemia were treated with a divided 15 g daily dose of colestipol, a bile acid sequestrant, for periods of up to 20 months. The patients were divided into 3 groups: Those with no obvious sequelae, those with arcus corneae, xanthomas, and/or xanthelasmas only, and those with atherosclerotic complications. Colestipol lowered plasma cholesterol in all 3 groups, but reduced it to normal or near-normal levels in only 9 of the 25 patients (36%). The response of plasma triglycerides was highly varible; the mean for each group was elevated by the drug. Colestipol was well-tolerated and its effect did not diminish with time. It is a useful drug in the treatment of hypercholesterolemia.", "contents": "Results of colestipol therapy in Type II hyperlipoproteinemia. Twenty-five patinets with well defined Type ii hyperlipoproteinemia were treated with a divided 15 g daily dose of colestipol, a bile acid sequestrant, for periods of up to 20 months. The patients were divided into 3 groups: Those with no obvious sequelae, those with arcus corneae, xanthomas, and/or xanthelasmas only, and those with atherosclerotic complications. Colestipol lowered plasma cholesterol in all 3 groups, but reduced it to normal or near-normal levels in only 9 of the 25 patients (36%). The response of plasma triglycerides was highly varible; the mean for each group was elevated by the drug. Colestipol was well-tolerated and its effect did not diminish with time. It is a useful drug in the treatment of hypercholesterolemia."} {"id": "PMID:182182", "title": "Cholesterol metabolism following portacaval shunt in the pig.", "content": "Portacaval shunting resulted in lower serum cholesterol and low density lipoprotein levels in comparison with values for littermate control pigs. Triglyceride levels were lower in the shunted animals only while receiving a low fat diet. The reductions in serum cholesterol and triglyceride levels of shunted pigs while receiving a standard pig diet were shown to be related to reduced hepatic synthesis of cholesterol and triglycerides.", "contents": "Cholesterol metabolism following portacaval shunt in the pig. Portacaval shunting resulted in lower serum cholesterol and low density lipoprotein levels in comparison with values for littermate control pigs. Triglyceride levels were lower in the shunted animals only while receiving a low fat diet. The reductions in serum cholesterol and triglyceride levels of shunted pigs while receiving a standard pig diet were shown to be related to reduced hepatic synthesis of cholesterol and triglycerides."} {"id": "PMID:182183", "title": "Lipid transport in the avian species. Part I. Isolation and characterization of apolipoproteins and major lipoprotein density classes of male turkey serum.", "content": "(1) Lipoproteins from the serum of male turkeys maintained on a normal diet were separated by sequential preparative ultracentrifugation into VLDL (d less than 1.006 g/ml), LDL (d = 1.006-1.063 g/ml), HDL (d = 1.063-1.21 g/ml) and VHDL (d greater than 1.21 g/ml). Lipoprotein density classes were characterized by analytical ultracentrifugation, agarose electrophoresis, immunodiffusion and immunoelectrophoresis, and by quantitative determination of protein, lipids and individual phosphatides. (2) HDL were the major density class representing 75% of the total lipoprotein content, LDL accounted for approximately 20% and VLDL for only 3-5% of the total lipoproteins. (3) VLDL were characterized by a relatively low content of glyceride (34%). Cholesterol esters were the major lipid (38%) of LDL, and the phospholipids (26%) of HDL. Glycerides of all major density classes consisted of equal amounts of triglycerides and diglycerides. (4) Phosphatidylcholine was the major phosphatide in all density classes. The composition of phosphatides was very similar in the VLDL and LDL, but it was different in the HDL. The ratio of phosphatidylcholine/sphingomyelin was higher in HDL than in VLDL and LD. (5) Immunological and electrophoretic studies showed that all three major density classes consisted of two lipoprotein families designated, in analogy to the human serum lipoprotein system [1], as LP-A and LP-B. The exception was HDL3 (d = 1.125-1.21 g/ml) which contained only LP-A. (6) ApoB was insoluble in aqueous buffers but could be solubilized after reduction and carboxymethylation. No C- or N-terminal amino acids were released by the usual chemical methods. The carbohydrate moiety of ApoB contained mannose, galactose and galactosamine. (7) ApoA consisted of a non-identical polypeptides designated in analogy to the human polypeptides as A-I and A-II. A-I was the major ApoA polypeptide and had a molecular weight of about 27,000. This polypeptide contained no half cystine, and the aspartic acid as the N-terminal and alanine as the C-terminal amino acids. A-II had a molecular weight of about 10,000, contained no half cystine and had alanine as the C-terminal amino acid. A-II showed no N-terminal amino acid by either dansylation, dinitrophenylation or Edman's procedure. Neither A-I nor A-II contained neutral sugars or hexosamines. (8) Concentrations of polypetides analogous to human ApoC, ApoD and \"arginine-rich\" polypeptide, if present, were too low for their unequivocal chemical characterization.", "contents": "Lipid transport in the avian species. Part I. Isolation and characterization of apolipoproteins and major lipoprotein density classes of male turkey serum. (1) Lipoproteins from the serum of male turkeys maintained on a normal diet were separated by sequential preparative ultracentrifugation into VLDL (d less than 1.006 g/ml), LDL (d = 1.006-1.063 g/ml), HDL (d = 1.063-1.21 g/ml) and VHDL (d greater than 1.21 g/ml). Lipoprotein density classes were characterized by analytical ultracentrifugation, agarose electrophoresis, immunodiffusion and immunoelectrophoresis, and by quantitative determination of protein, lipids and individual phosphatides. (2) HDL were the major density class representing 75% of the total lipoprotein content, LDL accounted for approximately 20% and VLDL for only 3-5% of the total lipoproteins. (3) VLDL were characterized by a relatively low content of glyceride (34%). Cholesterol esters were the major lipid (38%) of LDL, and the phospholipids (26%) of HDL. Glycerides of all major density classes consisted of equal amounts of triglycerides and diglycerides. (4) Phosphatidylcholine was the major phosphatide in all density classes. The composition of phosphatides was very similar in the VLDL and LDL, but it was different in the HDL. The ratio of phosphatidylcholine/sphingomyelin was higher in HDL than in VLDL and LD. (5) Immunological and electrophoretic studies showed that all three major density classes consisted of two lipoprotein families designated, in analogy to the human serum lipoprotein system [1], as LP-A and LP-B. The exception was HDL3 (d = 1.125-1.21 g/ml) which contained only LP-A. (6) ApoB was insoluble in aqueous buffers but could be solubilized after reduction and carboxymethylation. No C- or N-terminal amino acids were released by the usual chemical methods. The carbohydrate moiety of ApoB contained mannose, galactose and galactosamine. (7) ApoA consisted of a non-identical polypeptides designated in analogy to the human polypeptides as A-I and A-II. A-I was the major ApoA polypeptide and had a molecular weight of about 27,000. This polypeptide contained no half cystine, and the aspartic acid as the N-terminal and alanine as the C-terminal amino acids. A-II had a molecular weight of about 10,000, contained no half cystine and had alanine as the C-terminal amino acid. A-II showed no N-terminal amino acid by either dansylation, dinitrophenylation or Edman's procedure. Neither A-I nor A-II contained neutral sugars or hexosamines. (8) Concentrations of polypetides analogous to human ApoC, ApoD and \"arginine-rich\" polypeptide, if present, were too low for their unequivocal chemical characterization."} {"id": "PMID:182184", "title": "Lipid transport in the avian species. Part 2. Isolation and characterization of lipoprotein A and lipoprotein B, two major lipoprotein families of the male turkey serum lipoprotein system.", "content": "(1) Male turkey serum contains two major lipoprotein families designated as LP-A and LP-B in its lipoprotein density classes. These two lipoprotein families were separated from each of the lipoprotein density classes by affinity chromatography on concanavalin A-Sepharose 4B. LP-A was present in the unretained and LP-B in the retained fractions. Both lipoprotein families were characterized by determination of their immunological and electrophoretic properties, the flotation coefficient and chemical composition. (2) LPb was distributed over a wider density range than LP-A. Seventy-four percent of LP-B was found in the LDL, 17% IN The VLDL and 8% in the HDL. In contrast, 98% of LP-A was present in the HDL and 2% in the LDL fractions: there were only trace amounts of LP-A in the VLDL. (3)Immunological and electrophoretic studies showed that the protein moiety of LP-A contained only the two non-identical A-I and A-II polypeptides of ApoA. The protein moiety of LP-B consisted only of ApoB. (4) Isolation of LP-A and LP-B from the major lipoprotein density classes provided further experimental evidence to confirm the existence of chemically distinct lipoprotein families as the fundamental physical-chemical entities of the serum lipoprotein system.", "contents": "Lipid transport in the avian species. Part 2. Isolation and characterization of lipoprotein A and lipoprotein B, two major lipoprotein families of the male turkey serum lipoprotein system. (1) Male turkey serum contains two major lipoprotein families designated as LP-A and LP-B in its lipoprotein density classes. These two lipoprotein families were separated from each of the lipoprotein density classes by affinity chromatography on concanavalin A-Sepharose 4B. LP-A was present in the unretained and LP-B in the retained fractions. Both lipoprotein families were characterized by determination of their immunological and electrophoretic properties, the flotation coefficient and chemical composition. (2) LPb was distributed over a wider density range than LP-A. Seventy-four percent of LP-B was found in the LDL, 17% IN The VLDL and 8% in the HDL. In contrast, 98% of LP-A was present in the HDL and 2% in the LDL fractions: there were only trace amounts of LP-A in the VLDL. (3)Immunological and electrophoretic studies showed that the protein moiety of LP-A contained only the two non-identical A-I and A-II polypeptides of ApoA. The protein moiety of LP-B consisted only of ApoB. (4) Isolation of LP-A and LP-B from the major lipoprotein density classes provided further experimental evidence to confirm the existence of chemically distinct lipoprotein families as the fundamental physical-chemical entities of the serum lipoprotein system."} {"id": "PMID:182185", "title": "Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: effects of 2,2-dimethyl, 5(2, 5-xylyoxy) valeric acid therapy.", "content": "The effects of C1-719 on plasma lipid and lipoprotein concentrations have been examined in four patients with endogenous hypertriglyceridaemia maintained on an isocaloric diet for a period of 6 months. During therapy (400 mg/day) the mean plasma triglyceride and cholesterol concentrations were reduced by 35% and 15% respectively, while the administration of 800 mg/day reduced these by 49% and 31%. This hypolipidaemic effect was due to a reduction in the circulating level of very low density lipoproteins (VLDL) without a change in their composition. Before treatment the plasma VLDL triglyceride turnover, and FFA flux, were higher than that of normal subjects maintained on a similar diet. The plasma VLDL B-apoprotein turnover was similarly higher than in the controls. Administration of C1-719 decreased the plasma VLDL triglyceride turnover, FFA flux and VLDL B-approtein turnover. The drug reduced the insulin response following a glucose load with some decrease in glucose levels. The results suggest that the increase in plasma triglyceride concentration in patients with endogenous hypertriglyceridaemia is due to increased production of plasma VLDL triglyceride and its apoptein associated with an enhanced supply of FFA for hepatic triglyceride synthesis. C1-719 exerts a hypolipidaemic effect through a reduction of VLDL production, consequent upon inhibition of lipolysis as well as decreased synthesis of the apoprotein carrier. These effects could in part be explained by an improvement in peripheral tissue responsiveness to insulin and decreased exposure of the liver to high levels of insulin. However, a direct effect of the drug on adipose tissue and liver metabolism has to be considered.", "contents": "Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: effects of 2,2-dimethyl, 5(2, 5-xylyoxy) valeric acid therapy. The effects of C1-719 on plasma lipid and lipoprotein concentrations have been examined in four patients with endogenous hypertriglyceridaemia maintained on an isocaloric diet for a period of 6 months. During therapy (400 mg/day) the mean plasma triglyceride and cholesterol concentrations were reduced by 35% and 15% respectively, while the administration of 800 mg/day reduced these by 49% and 31%. This hypolipidaemic effect was due to a reduction in the circulating level of very low density lipoproteins (VLDL) without a change in their composition. Before treatment the plasma VLDL triglyceride turnover, and FFA flux, were higher than that of normal subjects maintained on a similar diet. The plasma VLDL B-apoprotein turnover was similarly higher than in the controls. Administration of C1-719 decreased the plasma VLDL triglyceride turnover, FFA flux and VLDL B-approtein turnover. The drug reduced the insulin response following a glucose load with some decrease in glucose levels. The results suggest that the increase in plasma triglyceride concentration in patients with endogenous hypertriglyceridaemia is due to increased production of plasma VLDL triglyceride and its apoptein associated with an enhanced supply of FFA for hepatic triglyceride synthesis. C1-719 exerts a hypolipidaemic effect through a reduction of VLDL production, consequent upon inhibition of lipolysis as well as decreased synthesis of the apoprotein carrier. These effects could in part be explained by an improvement in peripheral tissue responsiveness to insulin and decreased exposure of the liver to high levels of insulin. However, a direct effect of the drug on adipose tissue and liver metabolism has to be considered."} {"id": "PMID:182186", "title": "The formation of deoxycholic acid in patients with type II and IV hyperlipoproteinaemia.", "content": "The formation of deoxycholic acid (D) was studied in 8 patients with Type II hyperlipoproteinaemia and in 6 with Type IV hyperlipoproteinaemia, using orally administered [2.4--3H]cholic acid and [24--14C]deoxycholic acid. The diet was standardized and of natural type. The mean values for fractional turnover, pool size and D synthesis in the patients with Type II pattern were 0.23 days-1, 331 mg and 75 mg/day, respectively; in Type IV they were 0.39 days-1, 587 mg and 191 mg/day. Compared with a group of healthy subjects, the pool size and formation of D were normal in Type IV, but significantly reduced in Type II. The mean conversion of cholic acid into the circulating pool of D was calculated to be 37% in Type II, and 38% in Type IV patients. Both these values are within normal limits.", "contents": "The formation of deoxycholic acid in patients with type II and IV hyperlipoproteinaemia. The formation of deoxycholic acid (D) was studied in 8 patients with Type II hyperlipoproteinaemia and in 6 with Type IV hyperlipoproteinaemia, using orally administered [2.4--3H]cholic acid and [24--14C]deoxycholic acid. The diet was standardized and of natural type. The mean values for fractional turnover, pool size and D synthesis in the patients with Type II pattern were 0.23 days-1, 331 mg and 75 mg/day, respectively; in Type IV they were 0.39 days-1, 587 mg and 191 mg/day. Compared with a group of healthy subjects, the pool size and formation of D were normal in Type IV, but significantly reduced in Type II. The mean conversion of cholic acid into the circulating pool of D was calculated to be 37% in Type II, and 38% in Type IV patients. Both these values are within normal limits."} {"id": "PMID:182191", "title": "Murine leukaemia virus group-specific antigen in tumor-resistant tetraparental AKR reversible CBA/H-T6 chimaeras.", "content": "Various facts are now known about the relative lymphoma resistance of a group of tetraparental AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. Firstly, their tumour resistance is not due to the lack of the lymphomaprone AKR cells. Secondly, results showing titres of MuLV-gs antigen comparable with, and occasionally in excess of, those in the AKR suggest that the tumour resistance of the chimaeras is unlikely to be due to a lack of oncogenic leukaemia virus. However, in marked contrast to the AKR, antibody-viral antigen renal complexes in the chimaeras were minimal. Lack of viral antigens could not explain the relative lack of renal complexes. Absence of the corresponding anti-viral antibody is the most likely explanation and this has to be attributed to the CBA component of the tetraparental AKR reversible CBA/H-T6 chimaeras. We suggest that with tolerance to the leukaemia virus being maintained and in the absence of anti-viral antigenic complexes, tumour-specific sites can be recognized and thus tumours are eliminated. This hypothesis remains to be proven.", "contents": "Murine leukaemia virus group-specific antigen in tumor-resistant tetraparental AKR reversible CBA/H-T6 chimaeras. Various facts are now known about the relative lymphoma resistance of a group of tetraparental AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. Firstly, their tumour resistance is not due to the lack of the lymphomaprone AKR cells. Secondly, results showing titres of MuLV-gs antigen comparable with, and occasionally in excess of, those in the AKR suggest that the tumour resistance of the chimaeras is unlikely to be due to a lack of oncogenic leukaemia virus. However, in marked contrast to the AKR, antibody-viral antigen renal complexes in the chimaeras were minimal. Lack of viral antigens could not explain the relative lack of renal complexes. Absence of the corresponding anti-viral antibody is the most likely explanation and this has to be attributed to the CBA component of the tetraparental AKR reversible CBA/H-T6 chimaeras. We suggest that with tolerance to the leukaemia virus being maintained and in the absence of anti-viral antigenic complexes, tumour-specific sites can be recognized and thus tumours are eliminated. This hypothesis remains to be proven."} {"id": "PMID:182187", "title": "Effect of hypertension on the entry of 125 I-labelled low density lipoprotein into the aortic intima in normal-fed rabbits.", "content": "The entry of [125I]-labelled low density lipoprotein (LDL) into different regions of the aortic intima has been studied over a 6 hour period in both normotensive and renal hypertensive rabbits fed a normal diet. Studies have also been carried out in previously hypertensive rabbits in which the blood pressure was normalized with parenteral hydralazine during the six hour period, in which entry was studied. In the normotensive rabbits entry into the aortic intima was less than 1 mug of LDL protein/100 mg dry defatted weight over the 6 hour period with greatest entry into aortic arch intima and significantly less into both the thoracic and abdominal aortic intimae. Hypertension increased the entry into the arch and into aortic arch intimae. Hypertension increased the entry into the arch and into the thoracic and abdominal segments but this was only statistically significant for the aortic arch. The entry of [125I] LDL into the intima in those rabbits in which the hypertension had been normalized was similar to that for the hypertensive rabbits. The results suggest that hypertension in the normal fed rabbit increases lipoprotein entry into the arterial wall by an effect on vessel wall permeability rather than by a direct effect of filtration pressure.", "contents": "Effect of hypertension on the entry of 125 I-labelled low density lipoprotein into the aortic intima in normal-fed rabbits. The entry of [125I]-labelled low density lipoprotein (LDL) into different regions of the aortic intima has been studied over a 6 hour period in both normotensive and renal hypertensive rabbits fed a normal diet. Studies have also been carried out in previously hypertensive rabbits in which the blood pressure was normalized with parenteral hydralazine during the six hour period, in which entry was studied. In the normotensive rabbits entry into the aortic intima was less than 1 mug of LDL protein/100 mg dry defatted weight over the 6 hour period with greatest entry into aortic arch intima and significantly less into both the thoracic and abdominal aortic intimae. Hypertension increased the entry into the arch and into aortic arch intimae. Hypertension increased the entry into the arch and into the thoracic and abdominal segments but this was only statistically significant for the aortic arch. The entry of [125I] LDL into the intima in those rabbits in which the hypertension had been normalized was similar to that for the hypertensive rabbits. The results suggest that hypertension in the normal fed rabbit increases lipoprotein entry into the arterial wall by an effect on vessel wall permeability rather than by a direct effect of filtration pressure."} {"id": "PMID:182192", "title": "The innate resistance of CBA mice to endogenous murine leukaemia virus infection.", "content": "The incidence of lymphomata in CBA mice is low and furthermore is unaltered by transplantation at the early blastocyst stage and being born from the lymphoma-prone AKR. The number of C-type murine leukaemia virus particles in CBA derived in this manner and milk-fostered by AKR mice in no way differs from normal CBA. The results suggest that the oncogenic Gross virus does not pass through either the transplacental or transmammary routes, or alternatively that viral replication in the CBA was in some way inhibited. Both possibilities have still to be distinguished.", "contents": "The innate resistance of CBA mice to endogenous murine leukaemia virus infection. The incidence of lymphomata in CBA mice is low and furthermore is unaltered by transplantation at the early blastocyst stage and being born from the lymphoma-prone AKR. The number of C-type murine leukaemia virus particles in CBA derived in this manner and milk-fostered by AKR mice in no way differs from normal CBA. The results suggest that the oncogenic Gross virus does not pass through either the transplacental or transmammary routes, or alternatively that viral replication in the CBA was in some way inhibited. Both possibilities have still to be distinguished."} {"id": "PMID:182195", "title": "Crippling lung disease after measles and adenovirus infection.", "content": "Four children who developed severe lung disease after measles are described. One child died and three have been left with severe impairment of lung function. It is suggested that secondary infection with an adenovirus was responsible for causing the lung disease in these patients. The immune response to measles was abnormal. Measles virus may have rendered the children more susceptible to serious complications from infection with the adenovirus. The many deaths from 'measles pneumonia' in developing countries and the occasional occurence of post-measles bronchiectasis in this country may be due to secondary adenovirus infections. Further viral and serological studies are required to confirm this hypothesis.", "contents": "Crippling lung disease after measles and adenovirus infection. Four children who developed severe lung disease after measles are described. One child died and three have been left with severe impairment of lung function. It is suggested that secondary infection with an adenovirus was responsible for causing the lung disease in these patients. The immune response to measles was abnormal. Measles virus may have rendered the children more susceptible to serious complications from infection with the adenovirus. The many deaths from 'measles pneumonia' in developing countries and the occasional occurence of post-measles bronchiectasis in this country may be due to secondary adenovirus infections. Further viral and serological studies are required to confirm this hypothesis."} {"id": "PMID:182196", "title": "Factors influencing the response of Escherichia coli to antibiotics in conditions prevailing in the infected urinary bladder.", "content": "The response of a sensitive strain of Escherichia coli to a variety of antibiotics was examined in an in vitro model which simulates the hydrokinetic features of the urinary bladder. Recovery of bacterial cultures from antibiotic effects was observed following exposure to bactericidal and bacteristatic antibiotics and no substantial difference was noted between the effectiveness of bacteristatic and bactericidal agents except that bacteristatic antibiotics were more influenced by alteration of the conditions of \"diuresis\" and \"frequency of micturition\". The response of dense bacterial populations to high concentrations of 3 beta-lactam antibiotics varied markedly under the different hydrokinetic conditions. Possible reasons for these variations are discussed.", "contents": "Factors influencing the response of Escherichia coli to antibiotics in conditions prevailing in the infected urinary bladder. The response of a sensitive strain of Escherichia coli to a variety of antibiotics was examined in an in vitro model which simulates the hydrokinetic features of the urinary bladder. Recovery of bacterial cultures from antibiotic effects was observed following exposure to bactericidal and bacteristatic antibiotics and no substantial difference was noted between the effectiveness of bacteristatic and bactericidal agents except that bacteristatic antibiotics were more influenced by alteration of the conditions of \"diuresis\" and \"frequency of micturition\". The response of dense bacterial populations to high concentrations of 3 beta-lactam antibiotics varied markedly under the different hydrokinetic conditions. Possible reasons for these variations are discussed."} {"id": "PMID:182197", "title": "Status spongiousus resulting from intracerebral infection of mice with temperature-sensitive mutants of vesicular stomatitis virus.", "content": "Mice infected intracerebrally (i.c.) with wild-type (wt) VSV or temperature-sensitive (ts) mutants, ts 11, ts 22, ts 31 and ts 41, were studied for the development of histopathological lesions in the central nervous system (CNS). Mice infected i.c. with wt VSV exhibited histopathological lesions consisting principally of occasional foci of perivascular mononuclear cell infiltration and rare foci of necrosis. All wt VSV infected mice died within 2 days of i.c. inoculation. In contrast, mice infected i.c. with ts 22 and ts 31 developed spongiform lesions limited to the grey matter of the spinal cord beginning 4 days after inoculation. The spongiform lesions rapidly spread to involve the entire grey matter of the spinal cord by 5-7 days after infection. Vacuolar changes were restricted principally to neuronal processes and astrocytes. Ts 22 and ts 31 infected mice developed neurological illness beginning 4 days after infection and the majority of mice died by 7 days after infection. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and were devoid of neuro-pathological lesions at 4 and 8 days after infection.", "contents": "Status spongiousus resulting from intracerebral infection of mice with temperature-sensitive mutants of vesicular stomatitis virus. Mice infected intracerebrally (i.c.) with wild-type (wt) VSV or temperature-sensitive (ts) mutants, ts 11, ts 22, ts 31 and ts 41, were studied for the development of histopathological lesions in the central nervous system (CNS). Mice infected i.c. with wt VSV exhibited histopathological lesions consisting principally of occasional foci of perivascular mononuclear cell infiltration and rare foci of necrosis. All wt VSV infected mice died within 2 days of i.c. inoculation. In contrast, mice infected i.c. with ts 22 and ts 31 developed spongiform lesions limited to the grey matter of the spinal cord beginning 4 days after inoculation. The spongiform lesions rapidly spread to involve the entire grey matter of the spinal cord by 5-7 days after infection. Vacuolar changes were restricted principally to neuronal processes and astrocytes. Ts 22 and ts 31 infected mice developed neurological illness beginning 4 days after infection and the majority of mice died by 7 days after infection. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and were devoid of neuro-pathological lesions at 4 and 8 days after infection."} {"id": "PMID:182198", "title": "The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships.", "content": "1. The B-vitamin status of fifty-nine patients, mainly from the lower socio-economic classes in Bombay, with a history of chronic malnutrition, and of alcoholism of 1-5-20 years' duration, was studied before and during treatment, and in relation to their clinical, especially neurological, condition. These patients were divided into two neurological categories: (I) those with peripheral neuropathy (mainly sensory and distal) alone, (2) those with mental changes (mainly confusion and disorientation) also. Both categories frequently showed pellagrous pigmentation and mucocutaneous signs of B-vitamin deficiency. 2. Thiamin and erythrocyte transketolase (EC 2.2.1.1) activity, riboflavin, nicotinic acid, pantothenic acid, total and pyridoxal fraction of vitamin B6, folate and total vitamin B12 were estimated in the blood and the cerebrospinal fluid (CSF) of these patients, and also in the blood of sixty-nine control subjects and in the CSF of some of them. The concentrations of all the vitamins, except vitamin B12, were highly significantly lower in the blood of patients of category I compared to the controls, and erythrocyte transketolase activity and pyridoxal concentration in patients of category 2 were significantly lower than those of category I patients. Blood pantothenic acid and folate concentrations were reduced less consistently. 3. Serum vitamin B12 concentration was significantly increased (though within normal range) in the patients compared to the control group, probably because of the moderate hepatic insufficiency (as assessed by liver function tests) in the former. 4. The concentrations of thiamin, riboflavin, nicotinic acid and total vitamin B6 were also highly significantly lower in the CSF in patients of category I compared with controls. Furthermore, thiamin, nicotinic acid and total vitamin B6 concentrations were significantly lower in patients of category 2 than those of category I patients, indicating that CSF levels reflect better the neurological status of these patients. 5. There was a moderate increase in the blood concentration of all the vitamins tested, after a relatively poor hospital diet alone. There was a concurrent increase in the blood levels of thiamin, riboflavin, nicotinic acid and pantothenic acid after parenteral treatment with either thiamin or nicotinic acid. The administration of pyridoxine resulted in a significant increase in the blood levels of riboflavin and the pyridoxal fraction of vitamin B6.", "contents": "The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships. 1. The B-vitamin status of fifty-nine patients, mainly from the lower socio-economic classes in Bombay, with a history of chronic malnutrition, and of alcoholism of 1-5-20 years' duration, was studied before and during treatment, and in relation to their clinical, especially neurological, condition. These patients were divided into two neurological categories: (I) those with peripheral neuropathy (mainly sensory and distal) alone, (2) those with mental changes (mainly confusion and disorientation) also. Both categories frequently showed pellagrous pigmentation and mucocutaneous signs of B-vitamin deficiency. 2. Thiamin and erythrocyte transketolase (EC 2.2.1.1) activity, riboflavin, nicotinic acid, pantothenic acid, total and pyridoxal fraction of vitamin B6, folate and total vitamin B12 were estimated in the blood and the cerebrospinal fluid (CSF) of these patients, and also in the blood of sixty-nine control subjects and in the CSF of some of them. The concentrations of all the vitamins, except vitamin B12, were highly significantly lower in the blood of patients of category I compared to the controls, and erythrocyte transketolase activity and pyridoxal concentration in patients of category 2 were significantly lower than those of category I patients. Blood pantothenic acid and folate concentrations were reduced less consistently. 3. Serum vitamin B12 concentration was significantly increased (though within normal range) in the patients compared to the control group, probably because of the moderate hepatic insufficiency (as assessed by liver function tests) in the former. 4. The concentrations of thiamin, riboflavin, nicotinic acid and total vitamin B6 were also highly significantly lower in the CSF in patients of category I compared with controls. Furthermore, thiamin, nicotinic acid and total vitamin B6 concentrations were significantly lower in patients of category 2 than those of category I patients, indicating that CSF levels reflect better the neurological status of these patients. 5. There was a moderate increase in the blood concentration of all the vitamins tested, after a relatively poor hospital diet alone. There was a concurrent increase in the blood levels of thiamin, riboflavin, nicotinic acid and pantothenic acid after parenteral treatment with either thiamin or nicotinic acid. The administration of pyridoxine resulted in a significant increase in the blood levels of riboflavin and the pyridoxal fraction of vitamin B6."} {"id": "PMID:182199", "title": "Inhibition of estrogen-receptor-DNA interaction by intercalating drugs.", "content": "Ethidium bromide, an intercalating drug, was shown to inhibit the in vitro DNA binding of the uterine estradiol-receptor complex. The inhibition was reversible, dose dependent, complete for total saturation of DNA intercalating sites by the dye, and proportional to the extent of intercalated drug. The binding of the receptor to phosphocellulose and poly(adenylic acid)-cellulose was not decreased by this drug. Similar inhibition was also obtained with 9-hydroxyellipticine. Denatured DNA was more efficient at binding the estrogen receptor than phosphocellulose or poly(adenylic acid)-cellulose but less efficient than native DNA. We conclude that the DNA binding of the estrogen receptor cannot be simply interpreted in terms of electrostatic interactions but requires a particular double-helical structure of DNA.", "contents": "Inhibition of estrogen-receptor-DNA interaction by intercalating drugs. Ethidium bromide, an intercalating drug, was shown to inhibit the in vitro DNA binding of the uterine estradiol-receptor complex. The inhibition was reversible, dose dependent, complete for total saturation of DNA intercalating sites by the dye, and proportional to the extent of intercalated drug. The binding of the receptor to phosphocellulose and poly(adenylic acid)-cellulose was not decreased by this drug. Similar inhibition was also obtained with 9-hydroxyellipticine. Denatured DNA was more efficient at binding the estrogen receptor than phosphocellulose or poly(adenylic acid)-cellulose but less efficient than native DNA. We conclude that the DNA binding of the estrogen receptor cannot be simply interpreted in terms of electrostatic interactions but requires a particular double-helical structure of DNA."} {"id": "PMID:182200", "title": "Atherogenic hyperlipoproteinemia induced by cholesterol feeding the Patas monkey.", "content": "Patas monkeys were studied for 2 years on three dietary regimes: (1) commercial chow (control diet); (2) semipurified diet plus lard (fat-fed); and (3) semipurified diet plus lard and cholesterol (cholesterol-fed). The control and fat-fed animals had similar lipoproteins which were equivalent to the human very low density, low density (LDL), and high density lipoproteins. An additional lipoprotein referred to as LDL-II appeared to be equivalent to the human Lp(a). The cholesterol-fed animals developed accelerated atherosclerosis associated with a hypercholesterolemia which was characterized by (1) the appearance of beta-migrating lipoproteins (B=VLDL) in the d less than 1.006, (2) an increase in the intermediate lipoproteins and LDL, and (3) the appearance of LDL-II which contained a prominence of the arginine-rich apoprotein. The arginine-rich apoprotein was also a prominent component of the B-VLDL and intermediate lipoproteins. Characterization of this apoprotein revealed that it contained 11.5 mol % arginine, had a molecular weight of approximately 34 000, and coelectrophoresed with the arginine-rich apoprotein of man, dog, swine, rat, and rabbit.", "contents": "Atherogenic hyperlipoproteinemia induced by cholesterol feeding the Patas monkey. Patas monkeys were studied for 2 years on three dietary regimes: (1) commercial chow (control diet); (2) semipurified diet plus lard (fat-fed); and (3) semipurified diet plus lard and cholesterol (cholesterol-fed). The control and fat-fed animals had similar lipoproteins which were equivalent to the human very low density, low density (LDL), and high density lipoproteins. An additional lipoprotein referred to as LDL-II appeared to be equivalent to the human Lp(a). The cholesterol-fed animals developed accelerated atherosclerosis associated with a hypercholesterolemia which was characterized by (1) the appearance of beta-migrating lipoproteins (B=VLDL) in the d less than 1.006, (2) an increase in the intermediate lipoproteins and LDL, and (3) the appearance of LDL-II which contained a prominence of the arginine-rich apoprotein. The arginine-rich apoprotein was also a prominent component of the B-VLDL and intermediate lipoproteins. Characterization of this apoprotein revealed that it contained 11.5 mol % arginine, had a molecular weight of approximately 34 000, and coelectrophoresed with the arginine-rich apoprotein of man, dog, swine, rat, and rabbit."} {"id": "PMID:182201", "title": "Modification of membrane lipid: physical properties in relation to fatty acid structure.", "content": "Differential scanning calorimetry (DSC) and electron spin resonance (ESR) measurements were made to characterize how modifications in the fatty acid composition of Escherichia coli affected the thermotropic phase transition(s) of the membrane lipd. When the fatty acid composition contained between 20 and 60% saturated fatty acids, the DSC curves for isolated phospholipids and cytoplasmic membranes showed a broad (15-25 degree C) gel to liquid-crystalline phase transition, the position of which depended on the particular fatty acid composition. Utilizing multiple lipid mutants, enrichment of the membrane phospholipids with a single long-chain cis-monoenoic fatty acid in excess of that possible in a fatty acid levels less than 20% and gradually replaced the broad peak as the cis-monoenoic fatty acid content increased. These results were obtained with phospholipids, cytoplasmic membranes, and whole cells. With these same phopholipids, plots of 2,2,6,6-tetramethylpiperidinyl-1-oxy partitioning and ESR order parameters vs. 1/T revealed discontinuities at temperatures 40-60 degrees C above the calorimetrica-ly measured gel to liquid-crystalline phase transitions. Moreover, when the membrane phospholipids were enriched with certain combinations of cis-monenoic fatty acids (e.g., cis-delta 9-16:1 plus cis-delta 11-18:1) the DSC curve showed a broad gel to liquid crystalline phase change below 0 degrees C but the ESR studies revealed no discontinuities at temperatures above those of the gel to liquid-crystalline transition. These results demonstrated that enrichment of the membrane lipids with molecules in which both fatty acyl chains are identical cis-monoenoic residues led to a distinct type of liquid-crystalline phase. Furthermore, a general conclusion from this study is that Escherichia coli normally maintains a heterogeneous mixture of lipid molecules and, by so doing, prevents strong lipid-lipid associations that lead to the formation of lipid domains in the membrane.", "contents": "Modification of membrane lipid: physical properties in relation to fatty acid structure. Differential scanning calorimetry (DSC) and electron spin resonance (ESR) measurements were made to characterize how modifications in the fatty acid composition of Escherichia coli affected the thermotropic phase transition(s) of the membrane lipd. When the fatty acid composition contained between 20 and 60% saturated fatty acids, the DSC curves for isolated phospholipids and cytoplasmic membranes showed a broad (15-25 degree C) gel to liquid-crystalline phase transition, the position of which depended on the particular fatty acid composition. Utilizing multiple lipid mutants, enrichment of the membrane phospholipids with a single long-chain cis-monoenoic fatty acid in excess of that possible in a fatty acid levels less than 20% and gradually replaced the broad peak as the cis-monoenoic fatty acid content increased. These results were obtained with phospholipids, cytoplasmic membranes, and whole cells. With these same phopholipids, plots of 2,2,6,6-tetramethylpiperidinyl-1-oxy partitioning and ESR order parameters vs. 1/T revealed discontinuities at temperatures 40-60 degrees C above the calorimetrica-ly measured gel to liquid-crystalline phase transitions. Moreover, when the membrane phospholipids were enriched with certain combinations of cis-monenoic fatty acids (e.g., cis-delta 9-16:1 plus cis-delta 11-18:1) the DSC curve showed a broad gel to liquid crystalline phase change below 0 degrees C but the ESR studies revealed no discontinuities at temperatures above those of the gel to liquid-crystalline transition. These results demonstrated that enrichment of the membrane lipids with molecules in which both fatty acyl chains are identical cis-monoenoic residues led to a distinct type of liquid-crystalline phase. Furthermore, a general conclusion from this study is that Escherichia coli normally maintains a heterogeneous mixture of lipid molecules and, by so doing, prevents strong lipid-lipid associations that lead to the formation of lipid domains in the membrane."} {"id": "PMID:182202", "title": "Thermodynamic studies of binary and ternary complexes of pig heart lactate dehydrogenase.", "content": "The thermodynamics of the reaction catalyzed by pig heart muscle lactate dehydrogenase (LDH; EC1.1.1,27) have been studied in 0,2 M potassium phosphate buffer, pH 7, over the temperature range of 10 to 35 degrees C by using oxamate and oxalate to simulate the corresponding reactions of the substrates pyruvate and lactate, respectively. The various complexes formed are characterized by Gibbs free energies, enthalpies, and entropies. The Gibbs free energies were determined by equilibrium dialysis investigations, fluorescence titrations, and ultraviolet difference spectroscopy, while the reaction enthalpies stem from direct calorimetric measurements, Formulas are given for both the temperature dependence of the equilibrium constants and the variation with temperature of the enthalpies involved in the four reactions between LDH and NADH or NAD, LDH-NADH and oxamate, and LDH-NAD and oxalate. All reactions show a marked negative temperature coefficient, deltacp, of the binding enthalpies indicating partial refolding to be associated with binary and ternary complex formation. This interpretation appears very probable in view of recent x-ray crystallographic studies on lactate dehydrogenase from dogfish, which demonstrate a volume decrease to occur on binding of oxamate to the LDH-NADH complex. The validity of the thermodynamic parameters, as derived with substrate analogues, for the actual catalytic reaction, gains strong support from the agreement between the sum of the heats involved in the four intermediary reactions reported in this study and direct determinations of the overall enthalpy associated with the catalytic process published in the literature.", "contents": "Thermodynamic studies of binary and ternary complexes of pig heart lactate dehydrogenase. The thermodynamics of the reaction catalyzed by pig heart muscle lactate dehydrogenase (LDH; EC1.1.1,27) have been studied in 0,2 M potassium phosphate buffer, pH 7, over the temperature range of 10 to 35 degrees C by using oxamate and oxalate to simulate the corresponding reactions of the substrates pyruvate and lactate, respectively. The various complexes formed are characterized by Gibbs free energies, enthalpies, and entropies. The Gibbs free energies were determined by equilibrium dialysis investigations, fluorescence titrations, and ultraviolet difference spectroscopy, while the reaction enthalpies stem from direct calorimetric measurements, Formulas are given for both the temperature dependence of the equilibrium constants and the variation with temperature of the enthalpies involved in the four reactions between LDH and NADH or NAD, LDH-NADH and oxamate, and LDH-NAD and oxalate. All reactions show a marked negative temperature coefficient, deltacp, of the binding enthalpies indicating partial refolding to be associated with binary and ternary complex formation. This interpretation appears very probable in view of recent x-ray crystallographic studies on lactate dehydrogenase from dogfish, which demonstrate a volume decrease to occur on binding of oxamate to the LDH-NADH complex. The validity of the thermodynamic parameters, as derived with substrate analogues, for the actual catalytic reaction, gains strong support from the agreement between the sum of the heats involved in the four intermediary reactions reported in this study and direct determinations of the overall enthalpy associated with the catalytic process published in the literature."} {"id": "PMID:182203", "title": "Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase.", "content": "Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) FROM THE Novikoff hepatoma has been purified over 200 000-fold (based on the increase in specific activity), by ammonium sulfate fractionation and chromatography on DEAE-Sephadex, phosphocellulose, hydroxylapatite, and DNA-cellulose. The enzyme is remarkably stable through all stages of purification until DNA-cellulose chromatography when it must be kept in buffers containing 0.5 M NaCl and 1 mg/ml bovine serum albumin for stability. The enzyme appears to be homogeneous as evidenced by a single stainable band when subjected to electrophoresis in polyacrylamide gels of different porosity. The stainable band corresponds to the DNA polymerase as determined by slicing sister gels and assaying for enzyme activity. The specific activity of the homogeneous preparation is about 60 000 units/mg. The enzyme lacks detectable exonuclease or endonuclease activity. It has a molecular weight of 32 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. In sucrose gradients, the molecular weight is estimated at 31 000. The isoelectric point of the hydroxylapatite fraction enzyme is 8.5. The Novikoff beta-polymerase requires all four deoxyribonucleoside triphosphates, primer-template, and a divalent cation for maximal activity. The apparent Km for total deoxyribonucleoside triphosphate is 7-8 muM and for DNA 125 mug/ml. Activated DNA, rendered 7% acid soluble by DNase I, is the preferred primer-template, although a number of synthetic polynucleotides can by efficiently utilized, particularly in the presence of Mm2+ optimum is 7 mM; the Mn2+ optimum is 1 mM. The pH optimum is 8.4 in Tris-HCl or 9.2 in glycine buffer. The beta-polymerase is sstimulated about twofold by NaCl or KCl at an optimum of 50-100 MM, and the enzyme maintains considerable activity at high ionic strengths. The DNA polymerase is inhibited by ethanol, acetone, and a variety of known polymerase inhibitors. Glycols stimulate the enzyme as does spermine or spermidine. Unlike most beta-polymerases, the Novikoff enzyme is moderately sensitive to N-ethylmaleimide.", "contents": "Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase. Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) FROM THE Novikoff hepatoma has been purified over 200 000-fold (based on the increase in specific activity), by ammonium sulfate fractionation and chromatography on DEAE-Sephadex, phosphocellulose, hydroxylapatite, and DNA-cellulose. The enzyme is remarkably stable through all stages of purification until DNA-cellulose chromatography when it must be kept in buffers containing 0.5 M NaCl and 1 mg/ml bovine serum albumin for stability. The enzyme appears to be homogeneous as evidenced by a single stainable band when subjected to electrophoresis in polyacrylamide gels of different porosity. The stainable band corresponds to the DNA polymerase as determined by slicing sister gels and assaying for enzyme activity. The specific activity of the homogeneous preparation is about 60 000 units/mg. The enzyme lacks detectable exonuclease or endonuclease activity. It has a molecular weight of 32 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. In sucrose gradients, the molecular weight is estimated at 31 000. The isoelectric point of the hydroxylapatite fraction enzyme is 8.5. The Novikoff beta-polymerase requires all four deoxyribonucleoside triphosphates, primer-template, and a divalent cation for maximal activity. The apparent Km for total deoxyribonucleoside triphosphate is 7-8 muM and for DNA 125 mug/ml. Activated DNA, rendered 7% acid soluble by DNase I, is the preferred primer-template, although a number of synthetic polynucleotides can by efficiently utilized, particularly in the presence of Mm2+ optimum is 7 mM; the Mn2+ optimum is 1 mM. The pH optimum is 8.4 in Tris-HCl or 9.2 in glycine buffer. The beta-polymerase is sstimulated about twofold by NaCl or KCl at an optimum of 50-100 MM, and the enzyme maintains considerable activity at high ionic strengths. The DNA polymerase is inhibited by ethanol, acetone, and a variety of known polymerase inhibitors. Glycols stimulate the enzyme as does spermine or spermidine. Unlike most beta-polymerases, the Novikoff enzyme is moderately sensitive to N-ethylmaleimide."} {"id": "PMID:182204", "title": "Molecular mechanism of cardiotoxin action on axonal membranes.", "content": "Cardiotoxin isolated from Naja mossambica mossambica selectively deactivates the sodium-potassium activated adenosine triphosphatase of axonal membranes. Tetrodotoxin binding and acetylcholinesterase activities are unaffected by cardiotoxin treatment. The details of association of cardiotoxin with the axonal membrane were studied by following the deactivation of the sodium-potassium activated adenosine triphosphatase and by direct binding measurements with a tritiated derivative of the native cardiotoxin. The maximal binding capacity of the membrane is 42-50 nmol of cardiotoxin/mg of membrane protein. The high amount of binding suggests association of the toxin with the lipid phase of the membrane. It has been shown that cardiotoxin first associates rapidly and reversibly to membrane lipids, then, in a second step, it induces a rearrangement of the membrane structure which produces and irreversible deactivation of the sodium-potassium activated adenosine triphosphatase. Solubilization of the membrane-bound ATPase with Lubrol WX gives an active enzyme species that is resistant to cardiotoxin-induced deactivation. Cardiotoxin binding to the membrane is prevented by high concentrations of Ca 2+ and dibucaine. Although cardiotoxins and neurotoxins of cobra venom have large sequence homologies, their mode of action on membranes is very different. The cardiotoxin seems to bind to the lipid phase of the axonal membrane and inhibits the sodium-potassium activated adenosine triphosphatase, whereas the neurotoxin associates with a protein receptor in the post-synaptic membrane and blocks acetylcholine transmission.", "contents": "Molecular mechanism of cardiotoxin action on axonal membranes. Cardiotoxin isolated from Naja mossambica mossambica selectively deactivates the sodium-potassium activated adenosine triphosphatase of axonal membranes. Tetrodotoxin binding and acetylcholinesterase activities are unaffected by cardiotoxin treatment. The details of association of cardiotoxin with the axonal membrane were studied by following the deactivation of the sodium-potassium activated adenosine triphosphatase and by direct binding measurements with a tritiated derivative of the native cardiotoxin. The maximal binding capacity of the membrane is 42-50 nmol of cardiotoxin/mg of membrane protein. The high amount of binding suggests association of the toxin with the lipid phase of the membrane. It has been shown that cardiotoxin first associates rapidly and reversibly to membrane lipids, then, in a second step, it induces a rearrangement of the membrane structure which produces and irreversible deactivation of the sodium-potassium activated adenosine triphosphatase. Solubilization of the membrane-bound ATPase with Lubrol WX gives an active enzyme species that is resistant to cardiotoxin-induced deactivation. Cardiotoxin binding to the membrane is prevented by high concentrations of Ca 2+ and dibucaine. Although cardiotoxins and neurotoxins of cobra venom have large sequence homologies, their mode of action on membranes is very different. The cardiotoxin seems to bind to the lipid phase of the axonal membrane and inhibits the sodium-potassium activated adenosine triphosphatase, whereas the neurotoxin associates with a protein receptor in the post-synaptic membrane and blocks acetylcholine transmission."} {"id": "PMID:182205", "title": "Structure of an apolipoprotein-phospholipid complex: apoC-III induced changes in the physical properties of dimyristoylphosphatidylcholine.", "content": "The effect of ApoC-III, a major apoprotein constituent of human very low density lipoproteins, on the physical properties of dimyristoylphosphatidylcholine (DMPC) vesicles has been studied by magnetic resonance and fluorescence techniques. The sharp gel-liquid crystalline transition usually observed at 23 C in DMPC is both broadened and elevated when ApoC-III is bound as determined (a) from measurements of microscopic viscosity by pyrene excimer fluorescence, (b) from the distribution of di-tert-butyl nitroxide between the bulk aqueous phase and the fluid lipid phase, and (c) from the motion of fatty acyl chains of spin-labeled phosphatdylcholine. Experiments involving the translocation of ascorbate and charged nitroxide ions and the movement of paramagnetic Eu 3+ ions indicate that when ApoC-III binds to DMPC vesicles, it increases their permeability or destroys their original bilayer structure. These two possibilities were distinguishable by gel filtration of the DMPC-ApoC-III complex (approximately 34 mol mol) that indicated that the product particles were significantly smaller than the original vesicles. Taken together, the data indicate that ApoC-III binding to DMPC not only decreases the acyl chain motion of individual lipid molecules, but also induces break-down of bilamellar vesicular structure to give significantly smaller complexes.", "contents": "Structure of an apolipoprotein-phospholipid complex: apoC-III induced changes in the physical properties of dimyristoylphosphatidylcholine. The effect of ApoC-III, a major apoprotein constituent of human very low density lipoproteins, on the physical properties of dimyristoylphosphatidylcholine (DMPC) vesicles has been studied by magnetic resonance and fluorescence techniques. The sharp gel-liquid crystalline transition usually observed at 23 C in DMPC is both broadened and elevated when ApoC-III is bound as determined (a) from measurements of microscopic viscosity by pyrene excimer fluorescence, (b) from the distribution of di-tert-butyl nitroxide between the bulk aqueous phase and the fluid lipid phase, and (c) from the motion of fatty acyl chains of spin-labeled phosphatdylcholine. Experiments involving the translocation of ascorbate and charged nitroxide ions and the movement of paramagnetic Eu 3+ ions indicate that when ApoC-III binds to DMPC vesicles, it increases their permeability or destroys their original bilayer structure. These two possibilities were distinguishable by gel filtration of the DMPC-ApoC-III complex (approximately 34 mol mol) that indicated that the product particles were significantly smaller than the original vesicles. Taken together, the data indicate that ApoC-III binding to DMPC not only decreases the acyl chain motion of individual lipid molecules, but also induces break-down of bilamellar vesicular structure to give significantly smaller complexes."} {"id": "PMID:182206", "title": "The identity of a cyanogen bromide fragment of bovine dentin collagen containing the site of an intermolecular cross-link.", "content": "A peptide fraction isolated from a cyanogen bromide digest of bovine dentin collagen had a molecular weight of 46000. Its size and amino acid composition indicated that it could not consist of peptides derived from the cleavage of a single alpha chain. On reduction with tritiated sodium borohydride, radioactivity was incorporated primarily into 5, 5'-dihydroxylysinonorleucine without degradation at the peptide backbone. Periodate cleavage of the reduced or nonreduced peptide fraction generated one fragment of molecular weight 28000 and one of 18000 completely accounting for the size of the parent peptide. On amino acid analysis the constituent single-chain peptides were determined to be alpha2CB4 and alpha1CB6. Both peptides isolated after periodate oxidation of the tritiated borohydride reduced cross-link peptide were found to contain (3H)hydroxynorvaline. These data show that some hydroxylysine of alpha2CB4, a helical region peptide, was present in aldehyde form and could act as the aldehyde donor icross-link, Schiff's base formation. The only cross-linkage of this alpha2CB4 acting as an aldehyde donor peptide to alpha1CB6 would be a helical region to helical region bond, perhaps accounting for the unusual stability and low solubility of dentin collagen.", "contents": "The identity of a cyanogen bromide fragment of bovine dentin collagen containing the site of an intermolecular cross-link. A peptide fraction isolated from a cyanogen bromide digest of bovine dentin collagen had a molecular weight of 46000. Its size and amino acid composition indicated that it could not consist of peptides derived from the cleavage of a single alpha chain. On reduction with tritiated sodium borohydride, radioactivity was incorporated primarily into 5, 5'-dihydroxylysinonorleucine without degradation at the peptide backbone. Periodate cleavage of the reduced or nonreduced peptide fraction generated one fragment of molecular weight 28000 and one of 18000 completely accounting for the size of the parent peptide. On amino acid analysis the constituent single-chain peptides were determined to be alpha2CB4 and alpha1CB6. Both peptides isolated after periodate oxidation of the tritiated borohydride reduced cross-link peptide were found to contain (3H)hydroxynorvaline. These data show that some hydroxylysine of alpha2CB4, a helical region peptide, was present in aldehyde form and could act as the aldehyde donor icross-link, Schiff's base formation. The only cross-linkage of this alpha2CB4 acting as an aldehyde donor peptide to alpha1CB6 would be a helical region to helical region bond, perhaps accounting for the unusual stability and low solubility of dentin collagen."} {"id": "PMID:182207", "title": "An enzyme kinetics and 19F nuclear magnetic resonance study of selectively trifluoroacetylated cytochrome c derivatives.", "content": "The reaction of cytochrome c with ethyl thioltrifluoroacetate was carried out under conditions which led to the selective trifluoroacetylation of a small number of the 19 lysines. The mixture of derivatives was separated by ion-exchange chromatography and four different derivatives with well-resolved 19F nuclear magnetic resonance (NMR) spectra were obtained. Peptide mapping techniques indicated that one of these derivatives contained a single trifluoroacetyl group at lysine 22, and another derivative was singly labeled at lysine 25. The trifluoroacetylated lysine 22 derivative was fully active toward both succinate-cytochrome c reductase (EC 1.3.99.1) and cytochrome oxidase (EC 1.9.3.1) white the trifluoroacetylated lysine 25 derivative was fully active toward the reductase, but had a threefold greater Michaelis constant in the cytochrome oxidase reactin. This supports the hypothesis that the cytochrome oxidase binding site is located in the heme cervice region, and that Lys-25 is important in the binding. 19FNMR spectra of the cytochrome c derivatives bound to phospholipid vesicles were obtained. The reasonably narrow line widths (35-65 Hz) and good sensitivity of the trifluoroacetyl resonances indicated that they might be useful probes for the interaction of cytochrome c with intact mitochondria.", "contents": "An enzyme kinetics and 19F nuclear magnetic resonance study of selectively trifluoroacetylated cytochrome c derivatives. The reaction of cytochrome c with ethyl thioltrifluoroacetate was carried out under conditions which led to the selective trifluoroacetylation of a small number of the 19 lysines. The mixture of derivatives was separated by ion-exchange chromatography and four different derivatives with well-resolved 19F nuclear magnetic resonance (NMR) spectra were obtained. Peptide mapping techniques indicated that one of these derivatives contained a single trifluoroacetyl group at lysine 22, and another derivative was singly labeled at lysine 25. The trifluoroacetylated lysine 22 derivative was fully active toward both succinate-cytochrome c reductase (EC 1.3.99.1) and cytochrome oxidase (EC 1.9.3.1) white the trifluoroacetylated lysine 25 derivative was fully active toward the reductase, but had a threefold greater Michaelis constant in the cytochrome oxidase reactin. This supports the hypothesis that the cytochrome oxidase binding site is located in the heme cervice region, and that Lys-25 is important in the binding. 19FNMR spectra of the cytochrome c derivatives bound to phospholipid vesicles were obtained. The reasonably narrow line widths (35-65 Hz) and good sensitivity of the trifluoroacetyl resonances indicated that they might be useful probes for the interaction of cytochrome c with intact mitochondria."} {"id": "PMID:182208", "title": "Alterations in lipid acyl group composition and membrane structure in cells transformed by Rous sarcoma virus.", "content": "The acyl group composition of the phospholipids from normal chick embryo fibroblasts and from cells transformed by Rous sarcoma virus was determined by gas-liquid chromatography. Rous-transformed cells had less arachidonate (20:4) and more oleate (18:1) in membrane lipids than normal, growing cells. Normal density-inhibited cells had the lowest ratio of 18:1/20:4. Associated with the decreased content of 20:4 in the transformed cells was a decreased motional freedom of an incorporated spin-labeled fatty acid analogue. Arrhenius plots for uptake of 2-deoxyglucose revealed an increased apparent activation energy in the transformed cells, suggesting that the hexose transport carriers were sensitive to the changes in membrane composition and structure in fully transformed cells. However, the development of the changes in fatty acid composition occurred relatively slowly in the course of transformation, indicating that the observed compositional alterations are not likely to be a primary cause of the early changes in membrane function associated with malignant transformation.", "contents": "Alterations in lipid acyl group composition and membrane structure in cells transformed by Rous sarcoma virus. The acyl group composition of the phospholipids from normal chick embryo fibroblasts and from cells transformed by Rous sarcoma virus was determined by gas-liquid chromatography. Rous-transformed cells had less arachidonate (20:4) and more oleate (18:1) in membrane lipids than normal, growing cells. Normal density-inhibited cells had the lowest ratio of 18:1/20:4. Associated with the decreased content of 20:4 in the transformed cells was a decreased motional freedom of an incorporated spin-labeled fatty acid analogue. Arrhenius plots for uptake of 2-deoxyglucose revealed an increased apparent activation energy in the transformed cells, suggesting that the hexose transport carriers were sensitive to the changes in membrane composition and structure in fully transformed cells. However, the development of the changes in fatty acid composition occurred relatively slowly in the course of transformation, indicating that the observed compositional alterations are not likely to be a primary cause of the early changes in membrane function associated with malignant transformation."} {"id": "PMID:182209", "title": "Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing.", "content": "Valyl-tRNA synthetase from Bacillus stearothermophilus activates thereonine and forms a 1:1 complex with threonyl adenylate, but it does not catalyze the net formation of threonyl-tRNAVal at pH 7.78 and 25 degrees C in the quenched flow apparatus it decomposes at a rate constant of 36s-1. During this process there is a transient formation of Thr-tRNAVal reaching a maximum at 25 ms and rapidly falling to zero after 150 ms. At the peak, 22% of the (14C) threonine from the complex is present as (14C) Thr-tRNA. The reaction may be quenched with phenol and the partially mischarged tRNA isolated. The enzyme catalyzes its hydrolysis with a rate constant of 40s-1. The data fit a kinetic scheme in which 62% of the threonine from the threonyl adenylate is transferred to the tRNA. This may be compared with the rate constant of 12s-1 at which 84% of the valine is transferred to tRNAVal from the enzyme-bound valyl adenylate, and the rate constant of 0.015s-1 for the subsequent hydrolysis of Val-tRNAVal. Inhibition studies indicate a distinct second site for hydrolysis. The translocation of the aminoacyl moiety between the two sites could be mediated by a transfer between the 2'-and 3'-OH groups of the terminal adenosine fo the tRNA. The hyperspecificity of the enzyme is based on discriminating between the two competing substrates twice: once against the undesired substrate in the synthetic step, and once against the desired substrate in the destructive step.", "contents": "Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing. Valyl-tRNA synthetase from Bacillus stearothermophilus activates thereonine and forms a 1:1 complex with threonyl adenylate, but it does not catalyze the net formation of threonyl-tRNAVal at pH 7.78 and 25 degrees C in the quenched flow apparatus it decomposes at a rate constant of 36s-1. During this process there is a transient formation of Thr-tRNAVal reaching a maximum at 25 ms and rapidly falling to zero after 150 ms. At the peak, 22% of the (14C) threonine from the complex is present as (14C) Thr-tRNA. The reaction may be quenched with phenol and the partially mischarged tRNA isolated. The enzyme catalyzes its hydrolysis with a rate constant of 40s-1. The data fit a kinetic scheme in which 62% of the threonine from the threonyl adenylate is transferred to the tRNA. This may be compared with the rate constant of 12s-1 at which 84% of the valine is transferred to tRNAVal from the enzyme-bound valyl adenylate, and the rate constant of 0.015s-1 for the subsequent hydrolysis of Val-tRNAVal. Inhibition studies indicate a distinct second site for hydrolysis. The translocation of the aminoacyl moiety between the two sites could be mediated by a transfer between the 2'-and 3'-OH groups of the terminal adenosine fo the tRNA. The hyperspecificity of the enzyme is based on discriminating between the two competing substrates twice: once against the undesired substrate in the synthetic step, and once against the desired substrate in the destructive step."} {"id": "PMID:182210", "title": "Essential arginyl residues in fructose-1,6-bisphosphatase.", "content": "Modification of pig kidney fructose-1,6-bisphosphatase with 2,3-butanedione in borate buffer (pH 7.8) leads to the loss of the activation of the enzyme by monovalent cations, as well as to the loss of allosteric adenosine 5'-monophosphate (AMP) inhibition. In agreement with the results obtained for the butanedione modification of arginyl residues in other enzymes, the effects of modification can be reversed upon removal of excess butanedione and borate. Significant protection to the loss of K+ activation was afforded by the presence of the substrate fructose 1,6-bisphosphate, whereas AMP preferentially protected against the loss of AMP inhibition. The combination of both fructose 1,6-bisphosphate and AMP fully protected against the changes in enzyme properties on butanedione treatment. Under the latter conditions, one arginyl residue per mole of enzyme subunit was modified, whereas three arginyl residues were modified by butanedione under conditions leading to the loss of both potassium activation and AMP inhibition. Thus, the modification of two arginyl residues per subunit would appear to be responsible for the change in enzyme properties. The present results, as well as those of a previous report on the subject (Marcus, F. (1975), Biochemistry 14, 3916-3921) support the conclusion that one arginyl residue per subunit is essential for monovalent cation activation, and another arginyl residue is essential for AMP inhibition. A likely role of the latter residue could be its involvement in the binding of the phosphate group of AMP.", "contents": "Essential arginyl residues in fructose-1,6-bisphosphatase. Modification of pig kidney fructose-1,6-bisphosphatase with 2,3-butanedione in borate buffer (pH 7.8) leads to the loss of the activation of the enzyme by monovalent cations, as well as to the loss of allosteric adenosine 5'-monophosphate (AMP) inhibition. In agreement with the results obtained for the butanedione modification of arginyl residues in other enzymes, the effects of modification can be reversed upon removal of excess butanedione and borate. Significant protection to the loss of K+ activation was afforded by the presence of the substrate fructose 1,6-bisphosphate, whereas AMP preferentially protected against the loss of AMP inhibition. The combination of both fructose 1,6-bisphosphate and AMP fully protected against the changes in enzyme properties on butanedione treatment. Under the latter conditions, one arginyl residue per mole of enzyme subunit was modified, whereas three arginyl residues were modified by butanedione under conditions leading to the loss of both potassium activation and AMP inhibition. Thus, the modification of two arginyl residues per subunit would appear to be responsible for the change in enzyme properties. The present results, as well as those of a previous report on the subject (Marcus, F. (1975), Biochemistry 14, 3916-3921) support the conclusion that one arginyl residue per subunit is essential for monovalent cation activation, and another arginyl residue is essential for AMP inhibition. A likely role of the latter residue could be its involvement in the binding of the phosphate group of AMP."} {"id": "PMID:182211", "title": "Enveloped viruses as model membrane systems: microviscosity of vesicular stomatitis virus and host cell membranes.", "content": "The fluorescence probe 1,6-diphenyl-1,3,5-hexatriene was used to study and compare the dynamic properties of the hydrophobic region of vesicular stomatitis virus grown on L-929 cells, plasma membrane of L-929 cells prepared by two different methods, liposomes prepared from virus lipids and plasma membrane lipids, and intact L-929 cells. The rate of penetration of the probe into the hydrophobic region of the lipid bilayer was found to be much faster in the lipid vesicle bilayer as compared with the intact membrane, but in all cases the fluorescence anisotropy was constant with time. The L-cell plasma membranes, the vesicles prepared from the lipids derived from the plasma membranes, and intact cells are found to have much lower microviscosity values than the virus or virus lipid vesicles throughout a wide range of temperatures. The microviscosity of plasma membrane and plasma membrane lipid vesicles was found to depend on the procedure for plasma membrane preparation as the membranes prepared by different methods had different microviscosities. The intact virus and liposomes prepared from the virus lipids were found to have very similar microviscosity values. Plasma membrane and liposomes prepared from plasma membrane lipids also had similar microviscosity values. Factors affecting microviscosity in natural membranes and artificially mixed lipid membranes are discussed.", "contents": "Enveloped viruses as model membrane systems: microviscosity of vesicular stomatitis virus and host cell membranes. The fluorescence probe 1,6-diphenyl-1,3,5-hexatriene was used to study and compare the dynamic properties of the hydrophobic region of vesicular stomatitis virus grown on L-929 cells, plasma membrane of L-929 cells prepared by two different methods, liposomes prepared from virus lipids and plasma membrane lipids, and intact L-929 cells. The rate of penetration of the probe into the hydrophobic region of the lipid bilayer was found to be much faster in the lipid vesicle bilayer as compared with the intact membrane, but in all cases the fluorescence anisotropy was constant with time. The L-cell plasma membranes, the vesicles prepared from the lipids derived from the plasma membranes, and intact cells are found to have much lower microviscosity values than the virus or virus lipid vesicles throughout a wide range of temperatures. The microviscosity of plasma membrane and plasma membrane lipid vesicles was found to depend on the procedure for plasma membrane preparation as the membranes prepared by different methods had different microviscosities. The intact virus and liposomes prepared from the virus lipids were found to have very similar microviscosity values. Plasma membrane and liposomes prepared from plasma membrane lipids also had similar microviscosity values. Factors affecting microviscosity in natural membranes and artificially mixed lipid membranes are discussed."} {"id": "PMID:182212", "title": "Evidence for phase boundary lipid. Permeability of Tempo-choline into dimyristoylphosphatidylcholine vesicles at the phase transition.", "content": "The existence of distinct regions of mismatch in molecular packing at the interfaces of the fluid and ordered domains during the phase transition of dimyristoylphosphatidylcholine vesicles has been demonstrated by measuring the temperature dependence of the permeability to a spin-label cation and comparing this with a statistical mechanical calculation of the fraction of interfacial lipid. The kinetics of uptake and release of the 2,2,6,6-tetramethylpiperidinyl-1-oxycholine (Tempo-choline) spin label by single-bilayer dimyristoylphosphatidylcholine vesicles were measured using electron spin resonance spectroscopy to quantitate the amount of spin label present within the vesicles after removal of the external spin-label by ascorbate at 0 degrees C. Both the uptake and release experiments show that the Tempo-choline permeability peaks to a sharp maximum at the lipid-phase transition, the vesicles being almost impermeable to Tempo-choline below the transition and having a much reduced permeability above. The temperature profile of the permeability is in reasonable quantitative agreement with calculations of the fraction of interfacial boundary lipid from the Zimm and Bragg theory of cooperative transitions, which use independent spin-label measurements of the degree of transition to determine the cooperativity parameter. The relatively high intrinsic permeability of the interfacial regions (P approximately 0.2-1.0 X 10(-8) cm/s) is attributed to the mismatch in molecular packing of the lipid molecules at the ordered-fluid boundaries, which could have important implications not only for permeability in natural membranes (e.g., in transmitter release), but also for the function of membrane-bound enzymes and transport proteins.", "contents": "Evidence for phase boundary lipid. Permeability of Tempo-choline into dimyristoylphosphatidylcholine vesicles at the phase transition. The existence of distinct regions of mismatch in molecular packing at the interfaces of the fluid and ordered domains during the phase transition of dimyristoylphosphatidylcholine vesicles has been demonstrated by measuring the temperature dependence of the permeability to a spin-label cation and comparing this with a statistical mechanical calculation of the fraction of interfacial lipid. The kinetics of uptake and release of the 2,2,6,6-tetramethylpiperidinyl-1-oxycholine (Tempo-choline) spin label by single-bilayer dimyristoylphosphatidylcholine vesicles were measured using electron spin resonance spectroscopy to quantitate the amount of spin label present within the vesicles after removal of the external spin-label by ascorbate at 0 degrees C. Both the uptake and release experiments show that the Tempo-choline permeability peaks to a sharp maximum at the lipid-phase transition, the vesicles being almost impermeable to Tempo-choline below the transition and having a much reduced permeability above. The temperature profile of the permeability is in reasonable quantitative agreement with calculations of the fraction of interfacial boundary lipid from the Zimm and Bragg theory of cooperative transitions, which use independent spin-label measurements of the degree of transition to determine the cooperativity parameter. The relatively high intrinsic permeability of the interfacial regions (P approximately 0.2-1.0 X 10(-8) cm/s) is attributed to the mismatch in molecular packing of the lipid molecules at the ordered-fluid boundaries, which could have important implications not only for permeability in natural membranes (e.g., in transmitter release), but also for the function of membrane-bound enzymes and transport proteins."} {"id": "PMID:182213", "title": "Arthrobacter luteus restriction endonuclease recognition sequence and its cleavage map of SV40 DNA.", "content": "The nucleotide sequence at the cleavage site of the restriction endonuclease isolated from Arthrobacter luteus (Alu) has been determined. The endonuclease cleaves at the center of a palindromic tetranucleotide sequence to give even-ended duplex DNA fragments phosphorylated at the 5'-end. The endonuclease cleaves SV40 form I DNA into 32 fragments. The order and sizes of these fragments have been determined to provide an Alu cleavage map of the SV40 genome.", "contents": "Arthrobacter luteus restriction endonuclease recognition sequence and its cleavage map of SV40 DNA. The nucleotide sequence at the cleavage site of the restriction endonuclease isolated from Arthrobacter luteus (Alu) has been determined. The endonuclease cleaves at the center of a palindromic tetranucleotide sequence to give even-ended duplex DNA fragments phosphorylated at the 5'-end. The endonuclease cleaves SV40 form I DNA into 32 fragments. The order and sizes of these fragments have been determined to provide an Alu cleavage map of the SV40 genome."} {"id": "PMID:182214", "title": "Methionyl-tRNA synthetase from Escherichia coli: active stoichiometry and stopped-flow analysis of methionyl adenylate formaiton.", "content": "Native dimeric methionyl-tRNA synthetase and its monomeric proteolytic fragment are shown to form and to bind 1 mol of methyionyl adenylate per polypeptide chain. Moreover, at 25 degrees C, each monomer of the dimeric native enzyme behaves independently, exhibiting the same parameters for the methionine activation reaction as does the monomeric modified enzyme. These results were obtained using several independent methods including equilibrium and nonequilibrium dialysis, active site and tryptophan fluorescence titrations, and stopped-flow by fluorescence. Stopped-flow resolution of the reversible methionine activation reaction also demonstrates that methionine and ATP-Mg2+ react without coupling to form a ternary enzyme-methionine-ATP-Mg2+ complex. This complex readily converts to enzyme-methionyl approximately adenylate-PP-Mg2+ with a standard free energy close to zero. It is concluded that the uncoupled enzyme-methionine-ATP-Mg2+ complex may resemble the transition state of the reaction at the expense of the additional state of the reaction at the expense of the additional synergistic binding energy provided by reciprocal coupling, within the site, of the methionine molecule with the adenosine and PP-Mg2+ parts of the ATP-Mg2+ molecule (Blanguet, S., Fayat, G., and Waller, J. P. (1975), J. Mol. Biol. 94, 1.).", "contents": "Methionyl-tRNA synthetase from Escherichia coli: active stoichiometry and stopped-flow analysis of methionyl adenylate formaiton. Native dimeric methionyl-tRNA synthetase and its monomeric proteolytic fragment are shown to form and to bind 1 mol of methyionyl adenylate per polypeptide chain. Moreover, at 25 degrees C, each monomer of the dimeric native enzyme behaves independently, exhibiting the same parameters for the methionine activation reaction as does the monomeric modified enzyme. These results were obtained using several independent methods including equilibrium and nonequilibrium dialysis, active site and tryptophan fluorescence titrations, and stopped-flow by fluorescence. Stopped-flow resolution of the reversible methionine activation reaction also demonstrates that methionine and ATP-Mg2+ react without coupling to form a ternary enzyme-methionine-ATP-Mg2+ complex. This complex readily converts to enzyme-methionyl approximately adenylate-PP-Mg2+ with a standard free energy close to zero. It is concluded that the uncoupled enzyme-methionine-ATP-Mg2+ complex may resemble the transition state of the reaction at the expense of the additional state of the reaction at the expense of the additional synergistic binding energy provided by reciprocal coupling, within the site, of the methionine molecule with the adenosine and PP-Mg2+ parts of the ATP-Mg2+ molecule (Blanguet, S., Fayat, G., and Waller, J. P. (1975), J. Mol. Biol. 94, 1.)."} {"id": "PMID:182215", "title": "Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts.", "content": "The kinase active site of the aspartokinase-homoserine dehydrogenase enzyme complex of Excherichia coli has been affinity labeled both with substrates aspartate and adenosine triphosphate and feedback inhibitor threonine. Co(III) exchange-inert adducts of aspartokinase and inhibitor or substrates were produced in situ by oxidation of Co(II) with H2O2. Emzyme-Co(III)-adenosine 5'-triphosphate (ATP), enzyme-Co(III)-aspartate, and enzyme-Co(III)-threonine ternary adducts were produced in this manner. The formation of the enzyme-Co(III)-threonine adduct leads us to conclude that threonine inhibits the kinase activity of this enzyme complex by binding in the first coordination sphere of the catalytic metal ion cofactor, a conclusion which is consistent with evidence derived from previous nuclear magnetic resonance data obtained in this laboratory. The quaternary adducts formed by H2O2 oxidation in the presence of aspartokinase, Co(II), ATP, aspartate, and threonine comprised a mixture of both ezyme-Co(III)-ATP-aspartate and enzyme-Co(III)-ATP-threonine adducts. The formation of the quaternary aspartate-containing adduct was unexpected, since the presence of threonine was expected to prevent access of the aspartate to the active site; most significantly however, the the sum of the numbers of aspartate plus threonine molecules incorporated per active site is one. We believe that this shows direct steric overlap between the metal-adjacent binding sites for aspartate and threonine. Aspartate or threonine can not occupy the kinase active site simultaneously; this conclusion is consistent with the direct competitive inhibition of aspartate by threonine observed in steady-state kinetic studies.", "contents": "Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts. The kinase active site of the aspartokinase-homoserine dehydrogenase enzyme complex of Excherichia coli has been affinity labeled both with substrates aspartate and adenosine triphosphate and feedback inhibitor threonine. Co(III) exchange-inert adducts of aspartokinase and inhibitor or substrates were produced in situ by oxidation of Co(II) with H2O2. Emzyme-Co(III)-adenosine 5'-triphosphate (ATP), enzyme-Co(III)-aspartate, and enzyme-Co(III)-threonine ternary adducts were produced in this manner. The formation of the enzyme-Co(III)-threonine adduct leads us to conclude that threonine inhibits the kinase activity of this enzyme complex by binding in the first coordination sphere of the catalytic metal ion cofactor, a conclusion which is consistent with evidence derived from previous nuclear magnetic resonance data obtained in this laboratory. The quaternary adducts formed by H2O2 oxidation in the presence of aspartokinase, Co(II), ATP, aspartate, and threonine comprised a mixture of both ezyme-Co(III)-ATP-aspartate and enzyme-Co(III)-ATP-threonine adducts. The formation of the quaternary aspartate-containing adduct was unexpected, since the presence of threonine was expected to prevent access of the aspartate to the active site; most significantly however, the the sum of the numbers of aspartate plus threonine molecules incorporated per active site is one. We believe that this shows direct steric overlap between the metal-adjacent binding sites for aspartate and threonine. Aspartate or threonine can not occupy the kinase active site simultaneously; this conclusion is consistent with the direct competitive inhibition of aspartate by threonine observed in steady-state kinetic studies."} {"id": "PMID:182216", "title": "Binding of adenosine 3',5'-monophosphate dependent protein kinase regulatory subunit to immobilized cyclic nucleotide derivatives.", "content": "Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules.", "contents": "Binding of adenosine 3',5'-monophosphate dependent protein kinase regulatory subunit to immobilized cyclic nucleotide derivatives. Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules."} {"id": "PMID:182217", "title": "Substrate Binding of avian liver prenyltransferase.", "content": "Prenyltransferase (farnesyl pyrophosphate synthetase) was purified from avian liver and characterized by Sephadex and sodium dodecyl sulfate gel chromatography, peptide mapping, and end-group analysis. The enzyme is 85 800 +/- 4280 daltons and consists of two identical subunits as judged by sodium dodecyl sulfate gel electrophoresis, peptide mapping, and end-group analysis. Chemical analysis of the protein revealed no lipid or carbohydrate components. Avian prenyltransferase synthesizes farnesyl pyrophosphate from either dimethylallyl or geranyl pyrophosphate and isopentenyl pyrophosphate. A lower rate of geranylgeranyl pyrophosphate synthesis from farnesyl pyrophosphate and isopentenyl pyrophosphate was also demonstrated. Michaelis constants for farnesyl pyrophosphate synthesis are 0.5 muM for both isopentenyl pyrophosphate and geranyl pyrophosphate. The V max for the reaction is 1990 nmol min-1 mg-1 (170 mol min-1 mol-1 enzyme). Substrate inhibition by isopentenyl pyrophosphate is evident at high isopentenyl pyrophosphate and low geranyl pyrophosphate concentrations. Michaelis constants for geranylgeranyl pyrophosphate synthesis are 9 muM for farnesyl pyrophosphate and 20 muM for isopentenyl pyrophosphate. The Vmax is 16 nmol min-1 mg-1 (1.4 mol min-1 mol-1 enzyme). Two moles of each of the allylic substrates is bound per mol of enzyme. The apparent dissociation constants for dimethylallyl, geranyl, and farnesyl pyrophosphates are 1.8, 0.17, and 0.73 muM, respectively. Dimethylallyl and geranyl pyrophosphates bound competitively to prenyltransferase with one-for-one displacement. Four moles of isopentenyl pyrophosphate was bound per mole of enzyme. Citronellyl pyrophosphate, an analogue of geranyl pyrophosphate, was competitive with the binding of 2 of the 4 mol of isopentenyl pyrophosphate bound. The data are interpreted to indicate that each subunit of avian liver prenyltransferase has a single allylic binding site accommodating dimethylallyl, geranyl, and farnesyl pyrophosphates, and one binding site for isopentenyl pyrophosphate. In the absence of an allylic pyrophosphate or analogue, isopentenyl pyrophosphate also can bind to the allylic site.", "contents": "Substrate Binding of avian liver prenyltransferase. Prenyltransferase (farnesyl pyrophosphate synthetase) was purified from avian liver and characterized by Sephadex and sodium dodecyl sulfate gel chromatography, peptide mapping, and end-group analysis. The enzyme is 85 800 +/- 4280 daltons and consists of two identical subunits as judged by sodium dodecyl sulfate gel electrophoresis, peptide mapping, and end-group analysis. Chemical analysis of the protein revealed no lipid or carbohydrate components. Avian prenyltransferase synthesizes farnesyl pyrophosphate from either dimethylallyl or geranyl pyrophosphate and isopentenyl pyrophosphate. A lower rate of geranylgeranyl pyrophosphate synthesis from farnesyl pyrophosphate and isopentenyl pyrophosphate was also demonstrated. Michaelis constants for farnesyl pyrophosphate synthesis are 0.5 muM for both isopentenyl pyrophosphate and geranyl pyrophosphate. The V max for the reaction is 1990 nmol min-1 mg-1 (170 mol min-1 mol-1 enzyme). Substrate inhibition by isopentenyl pyrophosphate is evident at high isopentenyl pyrophosphate and low geranyl pyrophosphate concentrations. Michaelis constants for geranylgeranyl pyrophosphate synthesis are 9 muM for farnesyl pyrophosphate and 20 muM for isopentenyl pyrophosphate. The Vmax is 16 nmol min-1 mg-1 (1.4 mol min-1 mol-1 enzyme). Two moles of each of the allylic substrates is bound per mol of enzyme. The apparent dissociation constants for dimethylallyl, geranyl, and farnesyl pyrophosphates are 1.8, 0.17, and 0.73 muM, respectively. Dimethylallyl and geranyl pyrophosphates bound competitively to prenyltransferase with one-for-one displacement. Four moles of isopentenyl pyrophosphate was bound per mole of enzyme. Citronellyl pyrophosphate, an analogue of geranyl pyrophosphate, was competitive with the binding of 2 of the 4 mol of isopentenyl pyrophosphate bound. The data are interpreted to indicate that each subunit of avian liver prenyltransferase has a single allylic binding site accommodating dimethylallyl, geranyl, and farnesyl pyrophosphates, and one binding site for isopentenyl pyrophosphate. In the absence of an allylic pyrophosphate or analogue, isopentenyl pyrophosphate also can bind to the allylic site."} {"id": "PMID:182218", "title": "Effects of alpha-amanitin, cycloheximide, and thioacetamide on low molecular weight nuclear RNA.", "content": "Studies were made on the effects of alpha-amanitin, cycloheximide, and thioacetamide on synthesis and content of low molecular weight nuclear RNA. Cycloheximide, an inhibitor of protein synthesis and the synthesis of 45S pre-rRNA and 5S RNA, also inhibited synthesis of nuclear U1 and U3 RNAs. alpha-Amanitin, an inhibited the synthesis of U1 and U2 low molecular weight nuclear RNA. Thioacetamide, which induces nucleolar hypertrophy and increased nucleolar RNA polymerase activity, markedly increased synthesis of 5.8S RNA and U3 RNA. These results show that syntheses of individual low molecular weight nuclear (LMWN) RNAs are controlled by different regulatory mechanisms. In particular, there appears to be a specific relationship between U3 RNA and functional states of the nucleolus.", "contents": "Effects of alpha-amanitin, cycloheximide, and thioacetamide on low molecular weight nuclear RNA. Studies were made on the effects of alpha-amanitin, cycloheximide, and thioacetamide on synthesis and content of low molecular weight nuclear RNA. Cycloheximide, an inhibitor of protein synthesis and the synthesis of 45S pre-rRNA and 5S RNA, also inhibited synthesis of nuclear U1 and U3 RNAs. alpha-Amanitin, an inhibited the synthesis of U1 and U2 low molecular weight nuclear RNA. Thioacetamide, which induces nucleolar hypertrophy and increased nucleolar RNA polymerase activity, markedly increased synthesis of 5.8S RNA and U3 RNA. These results show that syntheses of individual low molecular weight nuclear (LMWN) RNAs are controlled by different regulatory mechanisms. In particular, there appears to be a specific relationship between U3 RNA and functional states of the nucleolus."} {"id": "PMID:182219", "title": "Spectroelectrochemical investigations of stoichiometry and oxidation-reduction potentials of cytochrome c oxidase components in the presence of carbon monoxide: the \"invisible\" copper.", "content": "Spectroelectrochemical studies are presented for the carbon monoxide complex of isolated, purified cytochrome c oxidase (EC 1.9.3.1) in solutions saturated with carbon monoxide. The results indicate a stoichiometry of three equivalents per oxidase-carbon monoxide complex molecule. Formal reduction potentials (Eo) of the two copper and one heme component at pH 7.0 were obtained by means of quantitative absorbance-charge titrations in the absence and presence of cytochrome c, and by means of a Nernstian \"Minnaert\" plot in the presence of cytochrome c. Analysis of the absorbance-charge curves from these titrations gave an indirect determination of the high potential, \"invisible\" copper component. The copper potentials in the carbon monoxide complex were found to be relatively unchanged with respect to those of the native enzyme. The Eo values obtained were: high potential (\"invisible\") copper (340 +/- 20 mV (NHE)), low potential copper (190 +/- 20 mV), and low potential heme (250 +/- 10 mV).", "contents": "Spectroelectrochemical investigations of stoichiometry and oxidation-reduction potentials of cytochrome c oxidase components in the presence of carbon monoxide: the \"invisible\" copper. Spectroelectrochemical studies are presented for the carbon monoxide complex of isolated, purified cytochrome c oxidase (EC 1.9.3.1) in solutions saturated with carbon monoxide. The results indicate a stoichiometry of three equivalents per oxidase-carbon monoxide complex molecule. Formal reduction potentials (Eo) of the two copper and one heme component at pH 7.0 were obtained by means of quantitative absorbance-charge titrations in the absence and presence of cytochrome c, and by means of a Nernstian \"Minnaert\" plot in the presence of cytochrome c. Analysis of the absorbance-charge curves from these titrations gave an indirect determination of the high potential, \"invisible\" copper component. The copper potentials in the carbon monoxide complex were found to be relatively unchanged with respect to those of the native enzyme. The Eo values obtained were: high potential (\"invisible\") copper (340 +/- 20 mV (NHE)), low potential copper (190 +/- 20 mV), and low potential heme (250 +/- 10 mV)."} {"id": "PMID:182220", "title": "Assignment of a ligand in stellacyanin by a pulsed electron paramagnetic resonance method.", "content": "The electron spin echo decay envelope for the blue copper protein, stellacyanin, and for a number of other Cu(II) complexes has been studied. Particular attention was given to the form of the \"nuclear modulation\" patterns, which show the effects of coupling between the electron spin and the neighboring nuclei. The envelopes for the hydrated cupric complex and for copper(II) glycylglycine were essentially the same and indicative of the coupling to protons. The peptide complex contains nitrogen nuclei coupled directly to Cu(II), but the coupling constant is so large for these nuclei that a modulation pattern ascribable to 14N is not seen. For copper(II) bovine serum albumin, on the other hand, a contribution due to the coupling of the remote nitrogen belonging to a histidyl imidazole ligand was observed. The modulation pattern for this complex and for stellacyanin closely resembled one another, strongly suggesting that an imidazole is ligated to the copper in this blue protein.", "contents": "Assignment of a ligand in stellacyanin by a pulsed electron paramagnetic resonance method. The electron spin echo decay envelope for the blue copper protein, stellacyanin, and for a number of other Cu(II) complexes has been studied. Particular attention was given to the form of the \"nuclear modulation\" patterns, which show the effects of coupling between the electron spin and the neighboring nuclei. The envelopes for the hydrated cupric complex and for copper(II) glycylglycine were essentially the same and indicative of the coupling to protons. The peptide complex contains nitrogen nuclei coupled directly to Cu(II), but the coupling constant is so large for these nuclei that a modulation pattern ascribable to 14N is not seen. For copper(II) bovine serum albumin, on the other hand, a contribution due to the coupling of the remote nitrogen belonging to a histidyl imidazole ligand was observed. The modulation pattern for this complex and for stellacyanin closely resembled one another, strongly suggesting that an imidazole is ligated to the copper in this blue protein."} {"id": "PMID:182221", "title": "Study of cytochrome oxidase co-binding site using low-temperature flash photolysis.", "content": "Flash photolysis has been used to study the kinetics of CO-binding to the heme alpha isolated cytochrome oxidase. Experiments performed over the range 185-295 degrees K with various CO concentrations have revealed significant deviations from the Arrhenius relationship between rate and temperature. These findings can be explained by a model in which the heme site is considered to have three regions between which CO can move; only from the innermost one can binding to the heme iron take place. The relative enthalpies and entropies of the three regions are calculated.", "contents": "Study of cytochrome oxidase co-binding site using low-temperature flash photolysis. Flash photolysis has been used to study the kinetics of CO-binding to the heme alpha isolated cytochrome oxidase. Experiments performed over the range 185-295 degrees K with various CO concentrations have revealed significant deviations from the Arrhenius relationship between rate and temperature. These findings can be explained by a model in which the heme site is considered to have three regions between which CO can move; only from the innermost one can binding to the heme iron take place. The relative enthalpies and entropies of the three regions are calculated."} {"id": "PMID:182222", "title": "Characteristics of the corticosterone-receptor complex in rat liver cytosol.", "content": "Using a gel filtration on Sephadex G-150 in low ionic strength, it was possible to separate a corticosterone-binding protein in rat liver cytosol from corticosteroid-binding globulin after incubation of cytosol with [3H]corticosterone. The corticosterone-protein complex (\"alpha-Complex\") had a sedimentation coefficient of 8-9 S in low ionic strength. In high ionic strength, the alpha-Complex rapidly dissociated with a half-life of 15 h, compared to a half-life of 31 h for the hepatic dexamethasone-receptor complex under identical conditions (0 degrees C). The alpha-Compelx was saturable with an excess of unlabelled corticosterone of dexamethasone and was sensitive to heat and protease digestion. It is stressed that quantitation of the corticosterone-receptor complex must include separation of the receptor from corticosteroid-binding globulin as this protein binds corticosterone with high affinity and with a saturable amount of binding sites.", "contents": "Characteristics of the corticosterone-receptor complex in rat liver cytosol. Using a gel filtration on Sephadex G-150 in low ionic strength, it was possible to separate a corticosterone-binding protein in rat liver cytosol from corticosteroid-binding globulin after incubation of cytosol with [3H]corticosterone. The corticosterone-protein complex (\"alpha-Complex\") had a sedimentation coefficient of 8-9 S in low ionic strength. In high ionic strength, the alpha-Complex rapidly dissociated with a half-life of 15 h, compared to a half-life of 31 h for the hepatic dexamethasone-receptor complex under identical conditions (0 degrees C). The alpha-Compelx was saturable with an excess of unlabelled corticosterone of dexamethasone and was sensitive to heat and protease digestion. It is stressed that quantitation of the corticosterone-receptor complex must include separation of the receptor from corticosteroid-binding globulin as this protein binds corticosterone with high affinity and with a saturable amount of binding sites."} {"id": "PMID:182223", "title": "Visible absorption spectra of quantum mixed-spin ferric heme proteins.", "content": "Recently, it has been shown that the magnetic data for Chromatium ferricytochrome c' at pH 7 are consistent with quantum mechanically (as distinguished from thermally) mixed mid-spin (S = 3/2) and high-spin (S = 5/2) heme. Visible absorption spectra of the protein measured at 77 degrees K and 293 degrees K, pH 7, show peaks at 400, 490, and 632 nm. The observation of a 630 nm band in quantum mixed-spin heme spectra, and the spin state-dependence of the band intensity, are discussed in the context of the iron-ligand structure for quantum mixed-spin heme inferred from magnetic data.", "contents": "Visible absorption spectra of quantum mixed-spin ferric heme proteins. Recently, it has been shown that the magnetic data for Chromatium ferricytochrome c' at pH 7 are consistent with quantum mechanically (as distinguished from thermally) mixed mid-spin (S = 3/2) and high-spin (S = 5/2) heme. Visible absorption spectra of the protein measured at 77 degrees K and 293 degrees K, pH 7, show peaks at 400, 490, and 632 nm. The observation of a 630 nm band in quantum mixed-spin heme spectra, and the spin state-dependence of the band intensity, are discussed in the context of the iron-ligand structure for quantum mixed-spin heme inferred from magnetic data."} {"id": "PMID:182224", "title": "Synthesis of inducible enzyme in Escherichia coli recovering from prolonged energy starvation.", "content": "A marked breakdown of ribosomes and rRNA occurs in Escherichia coli cells during prolonged deprivation of a carbon source (energy starvation). In E. coli recovering from energy starvation: (a) synthesis of RNA started immediately, total protein synthesis showed a delay of 5 to 10 minutes; (b) beta-galactosidase, tryptophanase and serine deaminase could not be induced in the first 50--70 min; (c) a lag of 60 min in the synthesis of beta-galactosidase was observed in a lac constitutive mutant of E. coli; synthesis of the constitutive enzyme malate dehydrogenase did not shown any delay. RNA synthesized in the early stages of recovery contained a higher percentage of low molecular weight molecules than RNA synthesized after 70 min of recovery or during exponential growth. Messenger RNA specific for beta-galactosidase was not synthesized for the first 50--60 min of recovery even when the specific inducer was added to the cultures.", "contents": "Synthesis of inducible enzyme in Escherichia coli recovering from prolonged energy starvation. A marked breakdown of ribosomes and rRNA occurs in Escherichia coli cells during prolonged deprivation of a carbon source (energy starvation). In E. coli recovering from energy starvation: (a) synthesis of RNA started immediately, total protein synthesis showed a delay of 5 to 10 minutes; (b) beta-galactosidase, tryptophanase and serine deaminase could not be induced in the first 50--70 min; (c) a lag of 60 min in the synthesis of beta-galactosidase was observed in a lac constitutive mutant of E. coli; synthesis of the constitutive enzyme malate dehydrogenase did not shown any delay. RNA synthesized in the early stages of recovery contained a higher percentage of low molecular weight molecules than RNA synthesized after 70 min of recovery or during exponential growth. Messenger RNA specific for beta-galactosidase was not synthesized for the first 50--60 min of recovery even when the specific inducer was added to the cultures."} {"id": "PMID:182225", "title": "Distribution of protein kinase activities in subcellular fractions of rat brain.", "content": "The subcellular distribution of histone and phosvitin kinase activities in brain has been studied and the ability of the various fractions to catalyse the phosphorylation of their endogenous proteins (intrinsic protein kinase activity) also examined. Synaptosome membrane fragments have little or no histone or phosvitin kinase activity but contain the highest concentration of cyclic AMP-stimulated intrinsic protein kinase activity. Homogenisation of the membrane fragments in Triton X-100 increased the histone kinase activity but on centrifugation it was all recovered in the supernatant, while the insoluble material contained all the intrinsic protein kinase activity. These results indicate that the intrinsic protein kinase activity of cerebral membrane fragments is due to the presence of a kinase enzyme which is specific to certain membrane proteins. The intrinsic protein kinase activity of synaptosome membrane fragments is a rather slow reaction which takes several minutes to saturate all the acceptor proteins.", "contents": "Distribution of protein kinase activities in subcellular fractions of rat brain. The subcellular distribution of histone and phosvitin kinase activities in brain has been studied and the ability of the various fractions to catalyse the phosphorylation of their endogenous proteins (intrinsic protein kinase activity) also examined. Synaptosome membrane fragments have little or no histone or phosvitin kinase activity but contain the highest concentration of cyclic AMP-stimulated intrinsic protein kinase activity. Homogenisation of the membrane fragments in Triton X-100 increased the histone kinase activity but on centrifugation it was all recovered in the supernatant, while the insoluble material contained all the intrinsic protein kinase activity. These results indicate that the intrinsic protein kinase activity of cerebral membrane fragments is due to the presence of a kinase enzyme which is specific to certain membrane proteins. The intrinsic protein kinase activity of synaptosome membrane fragments is a rather slow reaction which takes several minutes to saturate all the acceptor proteins."} {"id": "PMID:182226", "title": "Studies on the interaction of propranolol with erythrocyte membranes.", "content": "The interaction of propranolol with erythrocyte membranes at concentrations stabilizing intact erythrocytes against hypotonic hemolysis produced corresponding perturbations in membrane protein and particularly membrane phospholipid components as monitored by increases in the reactivity of membrane amino and sulfhydryl groups towards trinitrobenzenesulfonic acid and 5,5'-dithio-bis(2-nitro-benzoic acid), respectively. Membrane-propranolol interactions were also analyzed in terms of alterations produced in the kinetic properties of membrane enzymes. These experiments provided evidence that propranolol-induced perturbations were sufficiently generalized as to influence the activity of enzymatic processes associated with both inner and outer membrane surfaces. Configurational changes in membrane phospholipids were implicated in these effects of propranolol, which included alterations in functionally significant membrane-cation interactions, It is suggested that the findings described here may provide a basis for understanding molecular aspects of membrane stabilization in other systems.", "contents": "Studies on the interaction of propranolol with erythrocyte membranes. The interaction of propranolol with erythrocyte membranes at concentrations stabilizing intact erythrocytes against hypotonic hemolysis produced corresponding perturbations in membrane protein and particularly membrane phospholipid components as monitored by increases in the reactivity of membrane amino and sulfhydryl groups towards trinitrobenzenesulfonic acid and 5,5'-dithio-bis(2-nitro-benzoic acid), respectively. Membrane-propranolol interactions were also analyzed in terms of alterations produced in the kinetic properties of membrane enzymes. These experiments provided evidence that propranolol-induced perturbations were sufficiently generalized as to influence the activity of enzymatic processes associated with both inner and outer membrane surfaces. Configurational changes in membrane phospholipids were implicated in these effects of propranolol, which included alterations in functionally significant membrane-cation interactions, It is suggested that the findings described here may provide a basis for understanding molecular aspects of membrane stabilization in other systems."} {"id": "PMID:182227", "title": "A spin label study of rat brain membranes. Effects of temperature and divalent cations.", "content": "Rat brain myelin, synaptosomal plasma membranes and synaptic vesicles were spin labelled with stearic acid nitroxide derivatives. Their electron spin resonance spectra were studied as a function of temperature and devalent ions (Ca2+ and Mg2+) concentrations. (1) Synaptosomal plasma membranes and synaptic vesicles show identical temperature variations of their order parameter (S = 0.58 at 35 degrees C and S = 0.72 AT 22 DEGREES C). Myelin appears more rigid (S = 0.66 at 35 degrees C and S = 0.76 at 22 degrees C). A discontinuity of the order parameter variation as a function of temperature, is observed between 14.5 degrees C and l9.5 degrees C with the three types of membranes. (2) The hydrophobic core of these membranes is very fluid. No transition temperature is observed. The measured values of the spin label rotation correlation times and rotational activation energies are 2.1 and 2.8 ns at 35 degrees C and 3.1 and 3.6 kcal/mol respectively for synaptosomal plasma membranes and myelin. (3) Ca2+ enhances the membrane rigidity (12+/-0.7% increase of the order parameter at 35 degrees C in the presence of 10(-3) M Ca2+) and increases the transition temperature. At a lower extend, similar effects are observed with Mg2+.", "contents": "A spin label study of rat brain membranes. Effects of temperature and divalent cations. Rat brain myelin, synaptosomal plasma membranes and synaptic vesicles were spin labelled with stearic acid nitroxide derivatives. Their electron spin resonance spectra were studied as a function of temperature and devalent ions (Ca2+ and Mg2+) concentrations. (1) Synaptosomal plasma membranes and synaptic vesicles show identical temperature variations of their order parameter (S = 0.58 at 35 degrees C and S = 0.72 AT 22 DEGREES C). Myelin appears more rigid (S = 0.66 at 35 degrees C and S = 0.76 at 22 degrees C). A discontinuity of the order parameter variation as a function of temperature, is observed between 14.5 degrees C and l9.5 degrees C with the three types of membranes. (2) The hydrophobic core of these membranes is very fluid. No transition temperature is observed. The measured values of the spin label rotation correlation times and rotational activation energies are 2.1 and 2.8 ns at 35 degrees C and 3.1 and 3.6 kcal/mol respectively for synaptosomal plasma membranes and myelin. (3) Ca2+ enhances the membrane rigidity (12+/-0.7% increase of the order parameter at 35 degrees C in the presence of 10(-3) M Ca2+) and increases the transition temperature. At a lower extend, similar effects are observed with Mg2+."} {"id": "PMID:182228", "title": "Monamine oxidase in outer membrane of skeletal muscle mitochondria.", "content": "(1) Monoamine oxidase (EC 1.4.3.4) is present in rat skeletal muscle mitochondria. (2) A radioassay procedure for the assay of monoamine oxidase in muscle mitochondria is described. It is based on teh procedure using side-chain [2-14C]-tryptamine as substate described by Wurtman, R.J. and Axelrod, J. (1963) Biochem. Pharmacol. 12, 1439--1441 and employs a pH of 8.0 and a substrate concentration of 0.25 mM. (3) The Km of the muscle mitochondrial enzyme at pH 8.0 is 1.34 - 10(-5) M and that of the liver enzyme under the same conditions is 2.5 - 10(-5) M. Muscle mitochondria contain only one quarter of the activity of enzyme present in liver mitochondria. (4) Monoamine oxidase is shown to be in the outer membrane of skeletal muscle mitochondria and thus to be a suitable marker enzyme for use in the fractionation of these mitochondria.", "contents": "Monamine oxidase in outer membrane of skeletal muscle mitochondria. (1) Monoamine oxidase (EC 1.4.3.4) is present in rat skeletal muscle mitochondria. (2) A radioassay procedure for the assay of monoamine oxidase in muscle mitochondria is described. It is based on teh procedure using side-chain [2-14C]-tryptamine as substate described by Wurtman, R.J. and Axelrod, J. (1963) Biochem. Pharmacol. 12, 1439--1441 and employs a pH of 8.0 and a substrate concentration of 0.25 mM. (3) The Km of the muscle mitochondrial enzyme at pH 8.0 is 1.34 - 10(-5) M and that of the liver enzyme under the same conditions is 2.5 - 10(-5) M. Muscle mitochondria contain only one quarter of the activity of enzyme present in liver mitochondria. (4) Monoamine oxidase is shown to be in the outer membrane of skeletal muscle mitochondria and thus to be a suitable marker enzyme for use in the fractionation of these mitochondria."} {"id": "PMID:182229", "title": "Evidence for a secretion of thyroxine by isolated hog thyroid cells.", "content": "Isolated thyroid cells prepared from hog thyroid glands by tryptic dispersion were incubated with 131I- for 1--6 h. Free [131I]thyroxine was identified in the incubation medium by three chromatographic methods. Neither [131I]iodotyrosines nor [131I]triiodothyronine were detected. The [131I]thyroxine released in the medium by 100 mul of cells (packed cell volume) after a 6-h incubation period amounted to 1.16% (S.E. = +/- 0.39) of the total radioactivity. The medium [131I]thyroxine represented 15--25% of the total [131I]thyroxine synthesized during the 6 h of incubation. Thyrotropin, 1--60 munits/ml, increased the medium [131I]thyroxine content 2-4 fold. Dibutyryl cyclic AMP mimicked the effect of thyrotropin. The amount of medium [131]thyroxine was strictly related to the amount of incubated cells but was independent of the volume of the incubation medium. When prelabeled cells were incubated in the presence of methimazole the increase in medium [131I]thyroxine was quantitatively related to a decrease in the intracellular [131I]thyroxine. Addition of dinitrotyrosine, an inhibitor of the deiodinase activity, induced the release of iodotyrosines in the incubation medium. That the incubation supernatant of isolated thyroid cells did contain free thyroxine but not iodotyrosines suggests that the normal mechanisms of proteolysis of thyroglobulin and deiodination of iodotyrosines inside the cells are preserved. From these data, it was concluded that the thyroxine release by isolated cells represents a real secretion.", "contents": "Evidence for a secretion of thyroxine by isolated hog thyroid cells. Isolated thyroid cells prepared from hog thyroid glands by tryptic dispersion were incubated with 131I- for 1--6 h. Free [131I]thyroxine was identified in the incubation medium by three chromatographic methods. Neither [131I]iodotyrosines nor [131I]triiodothyronine were detected. The [131I]thyroxine released in the medium by 100 mul of cells (packed cell volume) after a 6-h incubation period amounted to 1.16% (S.E. = +/- 0.39) of the total radioactivity. The medium [131I]thyroxine represented 15--25% of the total [131I]thyroxine synthesized during the 6 h of incubation. Thyrotropin, 1--60 munits/ml, increased the medium [131I]thyroxine content 2-4 fold. Dibutyryl cyclic AMP mimicked the effect of thyrotropin. The amount of medium [131]thyroxine was strictly related to the amount of incubated cells but was independent of the volume of the incubation medium. When prelabeled cells were incubated in the presence of methimazole the increase in medium [131I]thyroxine was quantitatively related to a decrease in the intracellular [131I]thyroxine. Addition of dinitrotyrosine, an inhibitor of the deiodinase activity, induced the release of iodotyrosines in the incubation medium. That the incubation supernatant of isolated thyroid cells did contain free thyroxine but not iodotyrosines suggests that the normal mechanisms of proteolysis of thyroglobulin and deiodination of iodotyrosines inside the cells are preserved. From these data, it was concluded that the thyroxine release by isolated cells represents a real secretion."} {"id": "PMID:182230", "title": "Production of superoxide anion during the oxidation of hemoglobin by menadione.", "content": "Menadione in the presence of oxyhemoglobin will accelerate the formation of methemoglobin and result in the generation of superoxide anion. Menadione appears to oxidize slowly ferrohemoglobin to ferrihemoglobin, while forming menadione semiquinone in the process. Menadione semiquinone is known to react with molecular oxygen to yield superoxide anion. The superoxide anion appears to be the source of hydrogen peroxide which accounts for most of the observed methemoglobin formation when hemoglobin is reacted with menadione.", "contents": "Production of superoxide anion during the oxidation of hemoglobin by menadione. Menadione in the presence of oxyhemoglobin will accelerate the formation of methemoglobin and result in the generation of superoxide anion. Menadione appears to oxidize slowly ferrohemoglobin to ferrihemoglobin, while forming menadione semiquinone in the process. Menadione semiquinone is known to react with molecular oxygen to yield superoxide anion. The superoxide anion appears to be the source of hydrogen peroxide which accounts for most of the observed methemoglobin formation when hemoglobin is reacted with menadione."} {"id": "PMID:182231", "title": "Kinetic studies of Rhus vernicifera laccase. Evidence for multi-electron transfer and an oxygen intermediate in the reoxidation reaction.", "content": "1. The reoxidation of reduced Rhus vernicifera laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) by molecular oxygen has been studied by optical absorption and EPR methods. 2. The reoxidation by oxygen of the type 1 Cu+ and the two-electron acceptor is characterized by a second-order rate constant of about 5-10(6) M-1-s-1. 3. The appearance of an optical intermediate (with an absorbance maximum around 360 nm) parallels the reoxidation of type 1 Cu+ and the two-electron acceptor. It disappears in a first-order reaction with a half-time of 20 s. A similar intermediate is formed during normal turnover. 4. The type 2 Cu+ appears to be reoxidized in an intramolecular reaction with a half-time of about 20 s, suggesting a correlation between the reoxidation of this site and the disappearance of the optical intermediate. 5. The results suggest that three electrons are rapidly transferred to oxygen leading to the formation of an enzyme-bound oxygen intermediate.", "contents": "Kinetic studies of Rhus vernicifera laccase. Evidence for multi-electron transfer and an oxygen intermediate in the reoxidation reaction. 1. The reoxidation of reduced Rhus vernicifera laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) by molecular oxygen has been studied by optical absorption and EPR methods. 2. The reoxidation by oxygen of the type 1 Cu+ and the two-electron acceptor is characterized by a second-order rate constant of about 5-10(6) M-1-s-1. 3. The appearance of an optical intermediate (with an absorbance maximum around 360 nm) parallels the reoxidation of type 1 Cu+ and the two-electron acceptor. It disappears in a first-order reaction with a half-time of 20 s. A similar intermediate is formed during normal turnover. 4. The type 2 Cu+ appears to be reoxidized in an intramolecular reaction with a half-time of about 20 s, suggesting a correlation between the reoxidation of this site and the disappearance of the optical intermediate. 5. The results suggest that three electrons are rapidly transferred to oxygen leading to the formation of an enzyme-bound oxygen intermediate."} {"id": "PMID:182232", "title": "Protein kinases from liver mitochondria of tumour-bearing rats.", "content": "The mitochondria of liver of Yoshida ascites tumour-bearing rats contained two forms of protein kinase distinguishable on the basis of their kinetic properties, substrate specificity and responses to cyclic adenosine 3',5'-monophosphate (cAMP). One of these (kinase I) was activated 2-3 fold by cAMP while the other form (kinase II) was insensitive to the action of cAMP. Kinase I which was selective towards histone F1 as substrate was obtained as a homogeneous preparation and was observed to have a molecular weight of 170 000 by Sephadex G-150 gel filtration. Protein kinase II appeared to be a smaller protein with molecular weight of 54 000 and was specific towards acidic proteins namely casein and phosvitin. Protein kinases isolated from liver mitochondria of normal rats showed variations in respect to elution profile of DEAE-cellulose and electrophoretic mobility. The preparation corresponding to kinase I did not show stimulatory responses to cAMP.", "contents": "Protein kinases from liver mitochondria of tumour-bearing rats. The mitochondria of liver of Yoshida ascites tumour-bearing rats contained two forms of protein kinase distinguishable on the basis of their kinetic properties, substrate specificity and responses to cyclic adenosine 3',5'-monophosphate (cAMP). One of these (kinase I) was activated 2-3 fold by cAMP while the other form (kinase II) was insensitive to the action of cAMP. Kinase I which was selective towards histone F1 as substrate was obtained as a homogeneous preparation and was observed to have a molecular weight of 170 000 by Sephadex G-150 gel filtration. Protein kinase II appeared to be a smaller protein with molecular weight of 54 000 and was specific towards acidic proteins namely casein and phosvitin. Protein kinases isolated from liver mitochondria of normal rats showed variations in respect to elution profile of DEAE-cellulose and electrophoretic mobility. The preparation corresponding to kinase I did not show stimulatory responses to cAMP."} {"id": "PMID:182233", "title": "Human thyroid cyclic nucleotide phosphodiesterase. Its characterization and the effect of several hormones on the activity.", "content": "Cyclic AMP and cyclic GMP phosphodiesterase activities (3',5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) were investigated in the human thyroid gland from patients with hyperthyroidism. Low substrate concentration (0.4 muM) was used. About 60% of the cyclic-AMP and 80% of the cyclic-GMP hydrolytic activities in the homogenate were obtained in the soluble fraction (105 000 X g supernatant). The thyroid gland contains two forms of cyclic-AMP phosphodiesterase, one with a Km of 1.3-10(-5) M and the second with a Km of 2-10(-6) M. Cyclic-AMP and cyclic-GMP phosphodiesterase were purified by gel filtration on a Sepharose-6B column. Cyclic-AMP phosphodiesterase activities were found in a broad area corresponding to molecular weights ranging from approx. 200 000 to 250 000 and cyclic-GMP phosphodiesterase activity was found in a single area corresponding to a molecular weight of 260 000. Cyclis-AMP phosphodiesterase activities were stimulated by the protein activator which was found in human thyroid and this stimulation was dependent on Ca2+. Stimulation of cyclic-AMP phosphodiesterase by the activator was not significant even in the presence of enough Ca2+. The effect of D,L-triiodothyronine, D,L-thyroxine, L-diiodotyrosine, L-monoiodotyrosine, L-thyronine, L-diiodothyronine, thyrotropin, hydrocortisone, adrenocorticotropin, cyclic-AMP and cyclic-GMP on the phosphodiesterase activities was studied. Cyclic-AMP, cyclic-GMP, D,L-triiosothyronine, D,L-thyroxine, adrenocorticotropin and hydrocortisone where found to inhibit the phophodiesterase. Triiodothyronine and thyroxine inhibited cyclic-AMP phosphodiesterase more effectively than cyclic-GMP phosphodiesterase. Thyroxine was a more potent inhibitor than triiodothyronine. The concentration of cyclic AMP producing a 50% inhibition of cyclic-GMP phosphodiesterase activity was 5-10(-5) M, while the concentration of cyclic GMP producing a 50% inhibition of cyclic-AMP phosphodiesterase was 3-10(-3) M. Both cyclic-AMP and cyclic-GMP phosphodiesterase activities in the homogenate of hyperthyroidism, thyroid carcinoma and adenoma were higher than in normal thyroid tissue, when assayed with a low concentration of the substrate (0.4 muM). When a higher concentration (1 mM) of cyclic nucleotides was used as the substrate, cyclic-AMP hydrolytic activity in adenoma tissue was similar to that of normal tissue, while the other activities were higher than normal.", "contents": "Human thyroid cyclic nucleotide phosphodiesterase. Its characterization and the effect of several hormones on the activity. Cyclic AMP and cyclic GMP phosphodiesterase activities (3',5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) were investigated in the human thyroid gland from patients with hyperthyroidism. Low substrate concentration (0.4 muM) was used. About 60% of the cyclic-AMP and 80% of the cyclic-GMP hydrolytic activities in the homogenate were obtained in the soluble fraction (105 000 X g supernatant). The thyroid gland contains two forms of cyclic-AMP phosphodiesterase, one with a Km of 1.3-10(-5) M and the second with a Km of 2-10(-6) M. Cyclic-AMP and cyclic-GMP phosphodiesterase were purified by gel filtration on a Sepharose-6B column. Cyclic-AMP phosphodiesterase activities were found in a broad area corresponding to molecular weights ranging from approx. 200 000 to 250 000 and cyclic-GMP phosphodiesterase activity was found in a single area corresponding to a molecular weight of 260 000. Cyclis-AMP phosphodiesterase activities were stimulated by the protein activator which was found in human thyroid and this stimulation was dependent on Ca2+. Stimulation of cyclic-AMP phosphodiesterase by the activator was not significant even in the presence of enough Ca2+. The effect of D,L-triiodothyronine, D,L-thyroxine, L-diiodotyrosine, L-monoiodotyrosine, L-thyronine, L-diiodothyronine, thyrotropin, hydrocortisone, adrenocorticotropin, cyclic-AMP and cyclic-GMP on the phosphodiesterase activities was studied. Cyclic-AMP, cyclic-GMP, D,L-triiosothyronine, D,L-thyroxine, adrenocorticotropin and hydrocortisone where found to inhibit the phophodiesterase. Triiodothyronine and thyroxine inhibited cyclic-AMP phosphodiesterase more effectively than cyclic-GMP phosphodiesterase. Thyroxine was a more potent inhibitor than triiodothyronine. The concentration of cyclic AMP producing a 50% inhibition of cyclic-GMP phosphodiesterase activity was 5-10(-5) M, while the concentration of cyclic GMP producing a 50% inhibition of cyclic-AMP phosphodiesterase was 3-10(-3) M. Both cyclic-AMP and cyclic-GMP phosphodiesterase activities in the homogenate of hyperthyroidism, thyroid carcinoma and adenoma were higher than in normal thyroid tissue, when assayed with a low concentration of the substrate (0.4 muM). When a higher concentration (1 mM) of cyclic nucleotides was used as the substrate, cyclic-AMP hydrolytic activity in adenoma tissue was similar to that of normal tissue, while the other activities were higher than normal."} {"id": "PMID:182234", "title": "The estimation and comparison of molecular weight of angiotensin I converting enzyme by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis.", "content": "The angiotensin I converting enzyme from rat lung was observed to be a glycoprotein containing 8.3% carbohydrate and consisting of a single polypeptide chain with an estimated molecular weight of 139 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis and 150 000 by sucrose density gradient sedimentation analysis. A comparison of the mobility of angiotensin I converting enzyme from rat lung, rabbit lung, and two hog lung sources on sodium dodecyl sulfate-polyacrylamide gels indicates that all four enzymes have very similar molecular weights and subunit structures. Some previously reported molecular weight discrepancies appear to be due to anomalous behavior of the enzyme of gel filtration.", "contents": "The estimation and comparison of molecular weight of angiotensin I converting enzyme by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis. The angiotensin I converting enzyme from rat lung was observed to be a glycoprotein containing 8.3% carbohydrate and consisting of a single polypeptide chain with an estimated molecular weight of 139 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis and 150 000 by sucrose density gradient sedimentation analysis. A comparison of the mobility of angiotensin I converting enzyme from rat lung, rabbit lung, and two hog lung sources on sodium dodecyl sulfate-polyacrylamide gels indicates that all four enzymes have very similar molecular weights and subunit structures. Some previously reported molecular weight discrepancies appear to be due to anomalous behavior of the enzyme of gel filtration."} {"id": "PMID:182235", "title": "Effect of carbamidomethylation of cysteine residues G11(104)alpha on the properties of hemoglobin A.", "content": "A modified hemoglobin tetramer has been prepared containing carbamidomethylated G11(104)alpha cysteine residues. The molecule is electrophoretically identical to hemoglobin A, at pH 8.6, contains 2 titratable sulfhydryl groups per tetramer, and shows a normal oxygen affinity at half-saturation. However, the cooperative oxygen binding is significantly decreased. As the G11(104)alpha cysteine residues are located at the alpha1beta1 contact point in the hemoglobin tetramer, the results of this study indicate that modification within this portion of the molecule does not interfere with the assembly of subunits to form a tetramer or the resultant p50 but can cause a significant alteration of cooperative oxygen binding. In addition, spin-labels attached to this cysteine residue are not sensitive to changes in conformation which may take place at this contact point during oxygen binding. It is therefore possible that modification of the G11(104)alpha cysteine residue abolishes the contribution of the alpha1beta1 contact point to the cooperative oxygen binding phenomenon.", "contents": "Effect of carbamidomethylation of cysteine residues G11(104)alpha on the properties of hemoglobin A. A modified hemoglobin tetramer has been prepared containing carbamidomethylated G11(104)alpha cysteine residues. The molecule is electrophoretically identical to hemoglobin A, at pH 8.6, contains 2 titratable sulfhydryl groups per tetramer, and shows a normal oxygen affinity at half-saturation. However, the cooperative oxygen binding is significantly decreased. As the G11(104)alpha cysteine residues are located at the alpha1beta1 contact point in the hemoglobin tetramer, the results of this study indicate that modification within this portion of the molecule does not interfere with the assembly of subunits to form a tetramer or the resultant p50 but can cause a significant alteration of cooperative oxygen binding. In addition, spin-labels attached to this cysteine residue are not sensitive to changes in conformation which may take place at this contact point during oxygen binding. It is therefore possible that modification of the G11(104)alpha cysteine residue abolishes the contribution of the alpha1beta1 contact point to the cooperative oxygen binding phenomenon."} {"id": "PMID:182236", "title": "Conformational studies of corticotropin1-32 and constitutive peptides by circular dichroism.", "content": "Circular dichroism spectra on corticotropin1-32 and its constitutive N-, and C-terminal peptides are determined in water and trifluoroethanol under several conditions in the aromatic and peptide spectral regions. Furthermore, the effects of pH and varied mixtures of water-trifluoroethanol are examined on the corticotropin1-32 molecule. The results show that the N- and C-terminal series have a different behaviour in both aqueous and organic media. Corticotropin and the former peptides display \"random\" spectra in water, and alpha-helix type spectra in trifluoroethanol, while the latter have \"random\" spectra in both solvents. In the holopeptide corticotropin, the side chain-side chain effects, as reflected by the titration curves obtained from variations in the aromatic region, support the idea of an helical organization of part of the backbone even in aqueous solution. When going from water to trifluoroethanol corticotropin1-32 undergoes a conformational change which leads to an alpha-helix, following a linear pathway. These results, together with other observations, indicate the possible role of the conformation of corticotropin molecules in their biological life.", "contents": "Conformational studies of corticotropin1-32 and constitutive peptides by circular dichroism. Circular dichroism spectra on corticotropin1-32 and its constitutive N-, and C-terminal peptides are determined in water and trifluoroethanol under several conditions in the aromatic and peptide spectral regions. Furthermore, the effects of pH and varied mixtures of water-trifluoroethanol are examined on the corticotropin1-32 molecule. The results show that the N- and C-terminal series have a different behaviour in both aqueous and organic media. Corticotropin and the former peptides display \"random\" spectra in water, and alpha-helix type spectra in trifluoroethanol, while the latter have \"random\" spectra in both solvents. In the holopeptide corticotropin, the side chain-side chain effects, as reflected by the titration curves obtained from variations in the aromatic region, support the idea of an helical organization of part of the backbone even in aqueous solution. When going from water to trifluoroethanol corticotropin1-32 undergoes a conformational change which leads to an alpha-helix, following a linear pathway. These results, together with other observations, indicate the possible role of the conformation of corticotropin molecules in their biological life."} {"id": "PMID:182237", "title": "Resonance raman studies of a c type algal cytochrome. Deuterium shifts and a comparison with mammalian cytochrome c.", "content": "A c type cytochrome isolated from Synechococcus lividus grown on water and 2H2O media, has been studied by resonance Raman spectroscopy. The spectra were taken on the oxidized and reduced protein with excitation within the Soret band at 441.6 nm to determine whether individual resonance Raman bands of the heme shift upon deuterium substitution and also to provide a comparison with the spectra of horse heart cytochrome c. Some of the shifts observed with the deuterated heme c are larger than the corresponding shifts in meso-deuterated metalloporphyrins suggesting mixing of peripheral substituent vibrations with the skeletal modes of the porphyrin macrocycle. The algal cytochrome exhibits resonance Raman spectra roughly similar to those of horse heart cytochrome c, consistent with its optical absorption spectra which is typical of c type cytochromes, although a detailed comparison reveals note-worthy differences between the spectra of the two proteins; this may be a reflection of the effect of non-methionine ligands and protein environment on the vibrations of the c type heme in the algal cytochrome.", "contents": "Resonance raman studies of a c type algal cytochrome. Deuterium shifts and a comparison with mammalian cytochrome c. A c type cytochrome isolated from Synechococcus lividus grown on water and 2H2O media, has been studied by resonance Raman spectroscopy. The spectra were taken on the oxidized and reduced protein with excitation within the Soret band at 441.6 nm to determine whether individual resonance Raman bands of the heme shift upon deuterium substitution and also to provide a comparison with the spectra of horse heart cytochrome c. Some of the shifts observed with the deuterated heme c are larger than the corresponding shifts in meso-deuterated metalloporphyrins suggesting mixing of peripheral substituent vibrations with the skeletal modes of the porphyrin macrocycle. The algal cytochrome exhibits resonance Raman spectra roughly similar to those of horse heart cytochrome c, consistent with its optical absorption spectra which is typical of c type cytochromes, although a detailed comparison reveals note-worthy differences between the spectra of the two proteins; this may be a reflection of the effect of non-methionine ligands and protein environment on the vibrations of the c type heme in the algal cytochrome."} {"id": "PMID:182238", "title": "A structural study of pig liver glyceraldehyde-3-phosphate dehydrogenase.", "content": "A substantial portion of the primary structure of pig liver glyceraldehyde-3-phosphate dehydrogenase has been investigated and the results compared with those previously reported for the pig muscle enzyme. Liver and muscle glyceraldehyde-3-phosphate dehydrogenases show the same amino acid content, and the first N-terminal residues occur in the same sequence. No differences in N-terminal residues and amino acid composition have been evidenced by analysis of several tryptic peptides, which account for about 50% of the total amino acid sequence. From the electrophoretic mobilities of peptides T8 T9 and T25 it is concluded that residues Asp 60, Asp 67 and Glu 220 in the reported sequence of the pig muscle enzyme must be present as amides in the liver enzyme. The NAD+ content was found to be 2 mol per tetramer, while higher values have been reported for the muscle enzyme from various mammalian sources. The reactivity of lysyl side chains towards pyridoxal 5'-phosphate has been examined: the results indicate that Lys 212 is the main site reacted in fully inactivated pig liver holoenzyme. A similar result has been found for rabbit muscle apoenzyme, whereas rabbit muscle holoenzyme reacts at Lys 212 and 191.", "contents": "A structural study of pig liver glyceraldehyde-3-phosphate dehydrogenase. A substantial portion of the primary structure of pig liver glyceraldehyde-3-phosphate dehydrogenase has been investigated and the results compared with those previously reported for the pig muscle enzyme. Liver and muscle glyceraldehyde-3-phosphate dehydrogenases show the same amino acid content, and the first N-terminal residues occur in the same sequence. No differences in N-terminal residues and amino acid composition have been evidenced by analysis of several tryptic peptides, which account for about 50% of the total amino acid sequence. From the electrophoretic mobilities of peptides T8 T9 and T25 it is concluded that residues Asp 60, Asp 67 and Glu 220 in the reported sequence of the pig muscle enzyme must be present as amides in the liver enzyme. The NAD+ content was found to be 2 mol per tetramer, while higher values have been reported for the muscle enzyme from various mammalian sources. The reactivity of lysyl side chains towards pyridoxal 5'-phosphate has been examined: the results indicate that Lys 212 is the main site reacted in fully inactivated pig liver holoenzyme. A similar result has been found for rabbit muscle apoenzyme, whereas rabbit muscle holoenzyme reacts at Lys 212 and 191."} {"id": "PMID:182239", "title": "Calcium-binding proteins in electroplax and skeletal muscle. Comparison of the parvalbumin and phosphodiesterase activator protein of Electrophorus electricus.", "content": "A soluble calcium-binding protein has been isolated from the red skeletal muscle of the electric eel (Electrophorus electricus). The purification procedure involved ammonium sulfate precipitation, gel filtration on Sephadex G-75 in the presence of 45Ca2+, and chromatography on QAE-Sephadex. This procedure resulted in the isolation of a protein which was homogeneous upon polyacrylamide gel electrophoresis. The calcium-binding protein was found to be a typical parvalbumin by the following criteria: (1) molecular weight of 11 000; (2) pI of 4.7; (3) 1.9 mol Ca2+ bound per mol protein; Kd of approx. 10(-7) M; (4) no detectable phosphorus; (5) amino acid composition included nine residues of phenylalanine, single arginine, and no tyrosine or tryptophan; (6) ximax at 259 nm; (7) 260 nm:280 nm absorbance ratio of 4.78. Only one parvalbumin could be detected in muscle. Immunoprecipitation assay revealed that the parvalbumin was a major soluble component of skeletal muscle (0.10 mg/mg soluble protein), but could not be detected in liver, kidney, brain, spleen, heart or electroplax. Comparison of the parvalbumin with a calcium-binding protein previously isolated from electroplax revealed that the two proteins were different as judged by a variety of chemical criteria. These results suggest that during embryological development of electroplax the parvalbumin is lost and that it is not required for the function of electric tissue.", "contents": "Calcium-binding proteins in electroplax and skeletal muscle. Comparison of the parvalbumin and phosphodiesterase activator protein of Electrophorus electricus. A soluble calcium-binding protein has been isolated from the red skeletal muscle of the electric eel (Electrophorus electricus). The purification procedure involved ammonium sulfate precipitation, gel filtration on Sephadex G-75 in the presence of 45Ca2+, and chromatography on QAE-Sephadex. This procedure resulted in the isolation of a protein which was homogeneous upon polyacrylamide gel electrophoresis. The calcium-binding protein was found to be a typical parvalbumin by the following criteria: (1) molecular weight of 11 000; (2) pI of 4.7; (3) 1.9 mol Ca2+ bound per mol protein; Kd of approx. 10(-7) M; (4) no detectable phosphorus; (5) amino acid composition included nine residues of phenylalanine, single arginine, and no tyrosine or tryptophan; (6) ximax at 259 nm; (7) 260 nm:280 nm absorbance ratio of 4.78. Only one parvalbumin could be detected in muscle. Immunoprecipitation assay revealed that the parvalbumin was a major soluble component of skeletal muscle (0.10 mg/mg soluble protein), but could not be detected in liver, kidney, brain, spleen, heart or electroplax. Comparison of the parvalbumin with a calcium-binding protein previously isolated from electroplax revealed that the two proteins were different as judged by a variety of chemical criteria. These results suggest that during embryological development of electroplax the parvalbumin is lost and that it is not required for the function of electric tissue."} {"id": "PMID:182240", "title": "Platelet lipoproteins. A comparative study with serum lipoproteins.", "content": "The nature of human platelet lipoproteins was studied in two series of experiments. In the first series, whole platelets were utilized for extraction of lipoproteins by three different methods: chloroform/methanol/phenol; saline; or sucrose-gradient ultracentrifugation of platelet homogenates. By polyacrylamide gel electrophoresis we were able to demonstrate the existence of lipoprotein in the extracts obtained by the last two methods. These lipoproteins were found not to share antigenic determinants with alpha and beta serum lipoproteins. The second series of experiments utilized platelets solubilized either in sodium deoxycholate or sodium dodecyl sulfate. The solubilized product was characterized by double immunodiffusion and polyacrylamide gel electrophoresis. The nonidentity between plasma and platelet lipoproteins previously demonstrated in the first series of experiments was confirmed. This nonidentity was also supported by a comparison between the apoproteins of purified serum lipoproteins and platelet proteins released after solubilization with sodium dodecyl sulfate. No identical protein fractions were found. Our results suggest that, unlike erythrocyte membrane lipoproteins, the platelet lipoproteins are structurally different from plasma lipoproteins.", "contents": "Platelet lipoproteins. A comparative study with serum lipoproteins. The nature of human platelet lipoproteins was studied in two series of experiments. In the first series, whole platelets were utilized for extraction of lipoproteins by three different methods: chloroform/methanol/phenol; saline; or sucrose-gradient ultracentrifugation of platelet homogenates. By polyacrylamide gel electrophoresis we were able to demonstrate the existence of lipoprotein in the extracts obtained by the last two methods. These lipoproteins were found not to share antigenic determinants with alpha and beta serum lipoproteins. The second series of experiments utilized platelets solubilized either in sodium deoxycholate or sodium dodecyl sulfate. The solubilized product was characterized by double immunodiffusion and polyacrylamide gel electrophoresis. The nonidentity between plasma and platelet lipoproteins previously demonstrated in the first series of experiments was confirmed. This nonidentity was also supported by a comparison between the apoproteins of purified serum lipoproteins and platelet proteins released after solubilization with sodium dodecyl sulfate. No identical protein fractions were found. Our results suggest that, unlike erythrocyte membrane lipoproteins, the platelet lipoproteins are structurally different from plasma lipoproteins."} {"id": "PMID:182241", "title": "Studies on pig serum lipoproteins. III. Affinity chromatography of native lipoproteins on concanavalin A-sepharose.", "content": "The comparison of the binding capacities of the three major classes of pig serum lipoproteins, very low-density, low-density and high-density lipoproteins, to concanavalin A, was demonstrated by affinity chromatography on concanavalin A-Sepharose. Very low-density lipoprotein was separated into two fractions (60 to 66% of total protein was adsorbed). Each fraction had different electrophoretic mobility in pore size gradient gel. The majority of the carbohydrate was found in the adsorbed fraction. The carbohydrate content of the unadsorbed fraction was 0.14% sialic acid. 0.47% hexosamine and 0.93% neutral sugars, and of the adsorbed fraction, 2.05, 3.21 and 4.20%, respectively. The adsorbed and unadsorbed fractions contained fucose, mannose and galactose in the molar ratio of 1.0 : 3.6 +/- 0.2 : 2.2 +/- 0.4 and 1.0 : 3.1 +/- 0.2 : 2.5 +/- 0.3, respectively. Based on these results, two different molecular species were proved to be present in very low-density lipoproteins. In high-density lipoproteins, 80 to 85% of the total protein was not adsorbed on concanavalin A-Sepharose in spite of the presence of mannose in the apoprotein. In contrast to these lipoproteins, low-density lipoprotein was completely adsorbed on concanavalin A-Sepharose. However, the separation of the subfractions of low-density lipoprotein as well as the subfractions of high-density lipoprotein could not be achieved by this affinity column. The carbohydrate content of eluted fractions of low-density and high-density lipoproteins was identical with the previously reported values obtained in native lipoproteins. This difference in affinities for concanavalin A was also evidenced by gel electrophoretic profiles in urea and in sodium dodecyl sulfate which showed different glycoprotein distribution in each class of lipoproteins.", "contents": "Studies on pig serum lipoproteins. III. Affinity chromatography of native lipoproteins on concanavalin A-sepharose. The comparison of the binding capacities of the three major classes of pig serum lipoproteins, very low-density, low-density and high-density lipoproteins, to concanavalin A, was demonstrated by affinity chromatography on concanavalin A-Sepharose. Very low-density lipoprotein was separated into two fractions (60 to 66% of total protein was adsorbed). Each fraction had different electrophoretic mobility in pore size gradient gel. The majority of the carbohydrate was found in the adsorbed fraction. The carbohydrate content of the unadsorbed fraction was 0.14% sialic acid. 0.47% hexosamine and 0.93% neutral sugars, and of the adsorbed fraction, 2.05, 3.21 and 4.20%, respectively. The adsorbed and unadsorbed fractions contained fucose, mannose and galactose in the molar ratio of 1.0 : 3.6 +/- 0.2 : 2.2 +/- 0.4 and 1.0 : 3.1 +/- 0.2 : 2.5 +/- 0.3, respectively. Based on these results, two different molecular species were proved to be present in very low-density lipoproteins. In high-density lipoproteins, 80 to 85% of the total protein was not adsorbed on concanavalin A-Sepharose in spite of the presence of mannose in the apoprotein. In contrast to these lipoproteins, low-density lipoprotein was completely adsorbed on concanavalin A-Sepharose. However, the separation of the subfractions of low-density lipoprotein as well as the subfractions of high-density lipoprotein could not be achieved by this affinity column. The carbohydrate content of eluted fractions of low-density and high-density lipoproteins was identical with the previously reported values obtained in native lipoproteins. This difference in affinities for concanavalin A was also evidenced by gel electrophoretic profiles in urea and in sodium dodecyl sulfate which showed different glycoprotein distribution in each class of lipoproteins."} {"id": "PMID:182242", "title": "Determination of human apolipoprotein E by electroimmunoassay.", "content": "1. Apolipoprotein E (\"arginine-rich\" polypeptide) was isolated from delipidized human very low density lipoproteins by agarose column chromatography in the presence of 6 M guanidine-hydrochloride. 2. An electroimmunoassay (\"rocket\" electrophoresis) is described for quantitative determination of human serum apolipoprotein E. Purified apolipoprotein E was used for the preparation of monospecific antisera and standardization of assay. This sensitive, specific, rapid (time required for the completion of the assay is 5 h) and precise (the within- and between-assay coefficients of variation are 5 and 8%, respectively) assay is applicable to measurement of apolipoprotein E in whole serum and density classes. The results correlated well with those obtained by radial immunodiffusion (r = 0.85). 3. Serum apolipoprotein E levels of normal subjects and hyperlipoproteinemic phenotypes IIa, IIb and IV were the same (10 to 16 mg/100 ml). In contrast, patients with type III and V hyperlipoproteinemias had markedly elevated serum apolipoprotein E levels )27 and 25 mg/100 ml, respectively). The apolipoprotein E in serum of normolipidemic subjects was equally distributed among three major lipoprotein density classes: d less than 1.030 g/ml (27%), d 1.030-1.063 g/ml (36%)and d 1.063-1.21 g/ml (37%).", "contents": "Determination of human apolipoprotein E by electroimmunoassay. 1. Apolipoprotein E (\"arginine-rich\" polypeptide) was isolated from delipidized human very low density lipoproteins by agarose column chromatography in the presence of 6 M guanidine-hydrochloride. 2. An electroimmunoassay (\"rocket\" electrophoresis) is described for quantitative determination of human serum apolipoprotein E. Purified apolipoprotein E was used for the preparation of monospecific antisera and standardization of assay. This sensitive, specific, rapid (time required for the completion of the assay is 5 h) and precise (the within- and between-assay coefficients of variation are 5 and 8%, respectively) assay is applicable to measurement of apolipoprotein E in whole serum and density classes. The results correlated well with those obtained by radial immunodiffusion (r = 0.85). 3. Serum apolipoprotein E levels of normal subjects and hyperlipoproteinemic phenotypes IIa, IIb and IV were the same (10 to 16 mg/100 ml). In contrast, patients with type III and V hyperlipoproteinemias had markedly elevated serum apolipoprotein E levels )27 and 25 mg/100 ml, respectively). The apolipoprotein E in serum of normolipidemic subjects was equally distributed among three major lipoprotein density classes: d less than 1.030 g/ml (27%), d 1.030-1.063 g/ml (36%)and d 1.063-1.21 g/ml (37%)."} {"id": "PMID:182243", "title": "A major site of bicarbonate effect in system II reaction. Evidence from ESR signal IIvf, fast fluorescence yield changes and delayed light emission.", "content": "In order to determine the major site of bicarbonate action in the electron transport complex of Photosystem II, the following experimental techniques were used: electron spin resonance measurements of Signal IIvf, measurements of chlorophyll a fluorescence yield rise and decay kinetics, and delayed light emission decay. From data obtained using these experimental techniques the following conclusions were made: (1) absence of bicarbonate causes a reversible inactivation of up to 40% of Photosystem II reaction center activity; (2) there is no significant effect of bicarbonate on electron flow from the charge accumulating S state to Z; (3) there is no significant effect of bicarbonate on electron flow from Z to P-680+; (4) electron flow from Q-- to the intersystem electron transport pool is inhibited by from 4- to 6-fold under bicarbonate depletion conditions.", "contents": "A major site of bicarbonate effect in system II reaction. Evidence from ESR signal IIvf, fast fluorescence yield changes and delayed light emission. In order to determine the major site of bicarbonate action in the electron transport complex of Photosystem II, the following experimental techniques were used: electron spin resonance measurements of Signal IIvf, measurements of chlorophyll a fluorescence yield rise and decay kinetics, and delayed light emission decay. From data obtained using these experimental techniques the following conclusions were made: (1) absence of bicarbonate causes a reversible inactivation of up to 40% of Photosystem II reaction center activity; (2) there is no significant effect of bicarbonate on electron flow from the charge accumulating S state to Z; (3) there is no significant effect of bicarbonate on electron flow from Z to P-680+; (4) electron flow from Q-- to the intersystem electron transport pool is inhibited by from 4- to 6-fold under bicarbonate depletion conditions."} {"id": "PMID:182244", "title": "Energy-linked regulation of glucose and pyruvate oxidation in isolated perfused rat heart. Role of pyruvate dehydrogenase.", "content": "1. The regulation of glycolysis and pyruvate oxidation under varying conditions of ATP and oxygen consumption was studied in isolated perfused rat hearts. Potassium-induced arrest was employed to inhibit the ATP consumption of the heart. 2. Under the experimental conditions, the beating heart used solely glucose as the oxidisable substrate. The glycolytic flux through the aldolase step decreased in pace with the decreasing oxygen consumption during the potassium-induced arrest of the heart. The decrease in glucose oxidation was larger than the inhibition of the oxygen consumption, suggesting that the arrested heart switches to fatty acid oxidation. The time course and percentage changes of the inhibition of pyruvate oxidation and the decrease in the amount of the active form of pyruvate dehydrogenase suggest that the amount of active pyruvate dehydrogenase is the main regulator of pyruvate oxidation in the perfused heart. 3. To test the relative significance of the possible mechanisms regulating covalent interconversions of pyruvate dehydrogenase, the following parameters were measured in response to the potassium-induced cardiac arrest: concentrations of pyruvate, acetyl-CoA, CoA-SH, citrate, alpha-oxoglutarate, ATP, ADP, AMP, creatine, creatine phosphate and inorganic phosphate and the mitochondrial NADH/NAD+ ratio. In cardiac tissue the adenylate system is not a good indicator of the energy state of the mitochondrion, even when the concentrations of AMP and free cytosolic ADP are calculated from the adenylate kinase and creatine kinase equilibria. Only creatine phosphate and inorganic phosphate undergo significant changes, but evidence of the participation of the latter compounds in the regulation of the pyruvate dehydrogenase interconversions is lacking. The potassium-induced arrest of the heart resulted in a decrease in pyruvate, a slight increase in acetyl-CoA, a large increase in the concentration of citrate and an increase in the mitochondrial NADH/NAD+. The results can be interpreted as showing that in the heart, the pyruvate dehydrogenase interconversions are mainly regulated by the pyruvate concentration and the mitochondrial redox state. Concentrations of all the regulators tested shifted to directions which one would expect to result in a decrease in the amount of active pyruvate dehydrogenase, but the changes were quite small. Therefore, the energy-linked regulation of pyruvate dehydrogenase in intact tissue is possibly mediated by the equilibrium relations between the cellular redox state and the phosphorylation potential recently confirmed in cardiac tissue.", "contents": "Energy-linked regulation of glucose and pyruvate oxidation in isolated perfused rat heart. Role of pyruvate dehydrogenase. 1. The regulation of glycolysis and pyruvate oxidation under varying conditions of ATP and oxygen consumption was studied in isolated perfused rat hearts. Potassium-induced arrest was employed to inhibit the ATP consumption of the heart. 2. Under the experimental conditions, the beating heart used solely glucose as the oxidisable substrate. The glycolytic flux through the aldolase step decreased in pace with the decreasing oxygen consumption during the potassium-induced arrest of the heart. The decrease in glucose oxidation was larger than the inhibition of the oxygen consumption, suggesting that the arrested heart switches to fatty acid oxidation. The time course and percentage changes of the inhibition of pyruvate oxidation and the decrease in the amount of the active form of pyruvate dehydrogenase suggest that the amount of active pyruvate dehydrogenase is the main regulator of pyruvate oxidation in the perfused heart. 3. To test the relative significance of the possible mechanisms regulating covalent interconversions of pyruvate dehydrogenase, the following parameters were measured in response to the potassium-induced cardiac arrest: concentrations of pyruvate, acetyl-CoA, CoA-SH, citrate, alpha-oxoglutarate, ATP, ADP, AMP, creatine, creatine phosphate and inorganic phosphate and the mitochondrial NADH/NAD+ ratio. In cardiac tissue the adenylate system is not a good indicator of the energy state of the mitochondrion, even when the concentrations of AMP and free cytosolic ADP are calculated from the adenylate kinase and creatine kinase equilibria. Only creatine phosphate and inorganic phosphate undergo significant changes, but evidence of the participation of the latter compounds in the regulation of the pyruvate dehydrogenase interconversions is lacking. The potassium-induced arrest of the heart resulted in a decrease in pyruvate, a slight increase in acetyl-CoA, a large increase in the concentration of citrate and an increase in the mitochondrial NADH/NAD+. The results can be interpreted as showing that in the heart, the pyruvate dehydrogenase interconversions are mainly regulated by the pyruvate concentration and the mitochondrial redox state. Concentrations of all the regulators tested shifted to directions which one would expect to result in a decrease in the amount of active pyruvate dehydrogenase, but the changes were quite small. Therefore, the energy-linked regulation of pyruvate dehydrogenase in intact tissue is possibly mediated by the equilibrium relations between the cellular redox state and the phosphorylation potential recently confirmed in cardiac tissue."} {"id": "PMID:182245", "title": "Effects of colicins K and E1 on the glucose phosphotransferase system.", "content": "1. Glycerol-grown cells of Escherichia coli and its mutant uncA, treated with colicin E1 or K, exhibited a several-fold higher level of alpha-methylglucoside uptake than untreated cells. This stimulation was independent of the carbon source present during the uptake test. In a mutant strain that has elevated levels of alpha-methylglucoside accumulation the addition of colicin E1 or carbonylcyanide m-chlorophenylhydrazone (CCCP) did not further enhance the uptake. 2. Colicins K and E1 decreased the apparent Km for alpha-methylglucoside uptake significantly and increased the V about twofold. The exit of the glucoside was severely inhibited by the colicins. 3. In the presence of colicins, alpha-methylglucoside is still accumulated via the phosphoenolpyruvate-phosphotransferase system since no accumulation or phosphorylation occurs in an enzyme I mutant. The colicins increased the relative intracellular concentration of phosphorylated alpha-methylglucoside, possibly by inhibiting the dephosphorylation reaction, and caused an excretion of this compound. 4. The results are interpreted as indicating that energization of the membrane has an inhibitory effect on the phosphotransferase system. Possible modes of action are discussed.", "contents": "Effects of colicins K and E1 on the glucose phosphotransferase system. 1. Glycerol-grown cells of Escherichia coli and its mutant uncA, treated with colicin E1 or K, exhibited a several-fold higher level of alpha-methylglucoside uptake than untreated cells. This stimulation was independent of the carbon source present during the uptake test. In a mutant strain that has elevated levels of alpha-methylglucoside accumulation the addition of colicin E1 or carbonylcyanide m-chlorophenylhydrazone (CCCP) did not further enhance the uptake. 2. Colicins K and E1 decreased the apparent Km for alpha-methylglucoside uptake significantly and increased the V about twofold. The exit of the glucoside was severely inhibited by the colicins. 3. In the presence of colicins, alpha-methylglucoside is still accumulated via the phosphoenolpyruvate-phosphotransferase system since no accumulation or phosphorylation occurs in an enzyme I mutant. The colicins increased the relative intracellular concentration of phosphorylated alpha-methylglucoside, possibly by inhibiting the dephosphorylation reaction, and caused an excretion of this compound. 4. The results are interpreted as indicating that energization of the membrane has an inhibitory effect on the phosphotransferase system. Possible modes of action are discussed."} {"id": "PMID:182246", "title": "Respiratory components and oxidase activities in Alcaligenes eutrophus.", "content": "1. Cells of the hydrogen bacterium Alcaligenes eutrophus are broken by gentle lysis using lysozyme treatment in hypertonic sucrose followed by osmotic shock. By this method, 93% of the in vivo activity of the H2 oxidase is recovered and the ATPase remains particle bound. In contrast, cell disruption in a French pressure cell diminishes the in vivo activity of the H2 oxidase by 50% and solubilizes the bulk of the ATPase. 2. The bacterium contains a periplasmic cytochrome c with bands at 418, 521 and 550 nm (difference spectrum). In addition to cytochrome aa3, b-560, c-553 and o, low temperature difference spectra of membranes show the presence of two further cytochromes (shoulders at 551 and 553 nm). 3. The unsupplemented membrane fraction catalyses the oxidation of hydrogen, NADH, NADPH, succinate, formate and endogenous substrate (NAD linked) at rates 2--3-fold higher than membranes obtained from cells disrupted in a French pressure cell. With the exception of the H2 oxidase all oxidase activities in lysozyme membranes are sensitive to carbonylcyanide m-chlorophenylhydrazone (20-100% stimulation of oxygen uptake). 4. The cytoplasmic fraction contains a B-type cytochrome with absorption maxima at 436 and 560 nm, capable of combining with CO; it contains non-covalently bound protohaem. In alkaline solutions a spectral transition to the haemochrome type with bands at 423, 526 and 556 nm occurs. The addition of NADH to an aerobic suspension of this cytochrome elicits new absorption maxima at 418, 545 and 577 nm (difference spectrum), which are believed to represent an oxygenated form of the reduced cytochrome.", "contents": "Respiratory components and oxidase activities in Alcaligenes eutrophus. 1. Cells of the hydrogen bacterium Alcaligenes eutrophus are broken by gentle lysis using lysozyme treatment in hypertonic sucrose followed by osmotic shock. By this method, 93% of the in vivo activity of the H2 oxidase is recovered and the ATPase remains particle bound. In contrast, cell disruption in a French pressure cell diminishes the in vivo activity of the H2 oxidase by 50% and solubilizes the bulk of the ATPase. 2. The bacterium contains a periplasmic cytochrome c with bands at 418, 521 and 550 nm (difference spectrum). In addition to cytochrome aa3, b-560, c-553 and o, low temperature difference spectra of membranes show the presence of two further cytochromes (shoulders at 551 and 553 nm). 3. The unsupplemented membrane fraction catalyses the oxidation of hydrogen, NADH, NADPH, succinate, formate and endogenous substrate (NAD linked) at rates 2--3-fold higher than membranes obtained from cells disrupted in a French pressure cell. With the exception of the H2 oxidase all oxidase activities in lysozyme membranes are sensitive to carbonylcyanide m-chlorophenylhydrazone (20-100% stimulation of oxygen uptake). 4. The cytoplasmic fraction contains a B-type cytochrome with absorption maxima at 436 and 560 nm, capable of combining with CO; it contains non-covalently bound protohaem. In alkaline solutions a spectral transition to the haemochrome type with bands at 423, 526 and 556 nm occurs. The addition of NADH to an aerobic suspension of this cytochrome elicits new absorption maxima at 418, 545 and 577 nm (difference spectrum), which are believed to represent an oxygenated form of the reduced cytochrome."} {"id": "PMID:182248", "title": "Uptake of radiolabeled galactosyl-(alpha1 goes to 4)-galactosyl-(beta1 goes to 4)-glucosylceramide by human serum lipoproteins in vitro.", "content": "Human serum was exposed to various amounts of [6-3H] galactosyl-(alpha1 goes to 4)-galactosyl-(beta1 goes to 4)-glucosylceramide under standardized conditions in vitro, and the uptake of the lipid by serum lipoproteins was determined. Of the bound glycolipid, 2% was isolated with very low density, 24% with low density-, 47% with high density lipoproteins and 27% with the ultracentrifugal residue. The distribution was different from the distribution of endogenous galactosyl-galactosylglucosylceramide, indicating that the glycolipid is probably an integral part of the lipoprotein complexes in vivo.", "contents": "Uptake of radiolabeled galactosyl-(alpha1 goes to 4)-galactosyl-(beta1 goes to 4)-glucosylceramide by human serum lipoproteins in vitro. Human serum was exposed to various amounts of [6-3H] galactosyl-(alpha1 goes to 4)-galactosyl-(beta1 goes to 4)-glucosylceramide under standardized conditions in vitro, and the uptake of the lipid by serum lipoproteins was determined. Of the bound glycolipid, 2% was isolated with very low density, 24% with low density-, 47% with high density lipoproteins and 27% with the ultracentrifugal residue. The distribution was different from the distribution of endogenous galactosyl-galactosylglucosylceramide, indicating that the glycolipid is probably an integral part of the lipoprotein complexes in vivo."} {"id": "PMID:182249", "title": "Study of the lipid binding characteristics of the apolipoproteins from human high density lipoprotein. I. Electron microscopic and gel filtration studies with synthetic phosphatidylcholines.", "content": "The characteristics of the lipid - protein complex produced by the addition of the major apolipoproteins (apo AI and apo AII) of human high-density lipoprotein to synthetic phospholipids has been studied. Under the in vitro conditions utilized, apo AI binds to 1,2-dimyristoyl-sn-glycerophosphocholine and 1,2-dipalmitoyl-sn-glycerophosphocholine liposomes, but does not alter their morphologic characteristics. This binding occurs at temperatures above or below that of the transition (Tt) of the lipid bilayer. In contrast, apo AII spontaneously generates small, homogeneous disc-shaped lipid-protein complexes (50 X 10 a) from large phospholipid globules or from liposomes prepared with these lipids. This type of complex was only formed when the lipid/apo AII mixtures were warmed above the transition temperatures. The incorporation of apo AI into this small complex with apo AII may be greatly facilitated or inhibited depending on the sequence of addition of the various components. Under optimal circumstances, a maximum of 1 molecule of apo AI is incorporated with each molecule of apo A II into complexes with these two synthetic phospholipids.", "contents": "Study of the lipid binding characteristics of the apolipoproteins from human high density lipoprotein. I. Electron microscopic and gel filtration studies with synthetic phosphatidylcholines. The characteristics of the lipid - protein complex produced by the addition of the major apolipoproteins (apo AI and apo AII) of human high-density lipoprotein to synthetic phospholipids has been studied. Under the in vitro conditions utilized, apo AI binds to 1,2-dimyristoyl-sn-glycerophosphocholine and 1,2-dipalmitoyl-sn-glycerophosphocholine liposomes, but does not alter their morphologic characteristics. This binding occurs at temperatures above or below that of the transition (Tt) of the lipid bilayer. In contrast, apo AII spontaneously generates small, homogeneous disc-shaped lipid-protein complexes (50 X 10 a) from large phospholipid globules or from liposomes prepared with these lipids. This type of complex was only formed when the lipid/apo AII mixtures were warmed above the transition temperatures. The incorporation of apo AI into this small complex with apo AII may be greatly facilitated or inhibited depending on the sequence of addition of the various components. Under optimal circumstances, a maximum of 1 molecule of apo AI is incorporated with each molecule of apo A II into complexes with these two synthetic phospholipids."} {"id": "PMID:182250", "title": "Studies of the lipid binding characteristics of the apolipoproteins from human high density lipoprotein. II. Calorimetry of the binding of apo AI and apo AII with phospholipids.", "content": "The interactions of lysophosphatidylcholine and synthetic 1,2-dimyristoyl-sn-glycerophosphocholine (DMPC) liposomes with the isolated HDL-apolipoproteins, apo AI and apo AII, has been studied by microcalorimetry. Complex formation is a highly exothermal process characterized by a maximal enthalpy of about --200 kcal/mol of apoprotein when added to DMPC at 28 degrees C in 0.05 M sodium carbonate/bicarbonate buffer, pH 9.6. For the apo AI apoprotein, the binding consists of two processes, one endothermal occurring at low phospholipid/protein ratios and one exothermal predominant at higher phospholipid levels. The endothermal process has been attributed to a lipid-induced disaggregation of the apo AI while the exothermal process is similar to the binding of apo AII or apo HDL to phospholipids. The binding of a constant AI and apo AII, demonstrates the existence of a maximal association at a 1 : 1 molar ratio of the apolipoproteins. The sequential binding of DMPC to apo AI and apo AII suggests the existence of cooperativity between the two apoproteins in phospholipid binding as apo AII promotes the incorporation of apo AI into a protein-phospholipid complex.", "contents": "Studies of the lipid binding characteristics of the apolipoproteins from human high density lipoprotein. II. Calorimetry of the binding of apo AI and apo AII with phospholipids. The interactions of lysophosphatidylcholine and synthetic 1,2-dimyristoyl-sn-glycerophosphocholine (DMPC) liposomes with the isolated HDL-apolipoproteins, apo AI and apo AII, has been studied by microcalorimetry. Complex formation is a highly exothermal process characterized by a maximal enthalpy of about --200 kcal/mol of apoprotein when added to DMPC at 28 degrees C in 0.05 M sodium carbonate/bicarbonate buffer, pH 9.6. For the apo AI apoprotein, the binding consists of two processes, one endothermal occurring at low phospholipid/protein ratios and one exothermal predominant at higher phospholipid levels. The endothermal process has been attributed to a lipid-induced disaggregation of the apo AI while the exothermal process is similar to the binding of apo AII or apo HDL to phospholipids. The binding of a constant AI and apo AII, demonstrates the existence of a maximal association at a 1 : 1 molar ratio of the apolipoproteins. The sequential binding of DMPC to apo AI and apo AII suggests the existence of cooperativity between the two apoproteins in phospholipid binding as apo AII promotes the incorporation of apo AI into a protein-phospholipid complex."} {"id": "PMID:182251", "title": "Phospholipid biosynthesis in sarcoplasmic reticulum membrane during development.", "content": "Biosynthesis of phosphatidic acid, phosphatidylcholine and phosphatidylethanolamine in the sarcoplasmic reticulum membrane has been investigated. The results show that sarcoplasmic reticulum, in addition to its main function, i.e. transport and accumulation of Ca2+, is able to synthetize phospholipids by the same pathways as endoplasmic reticulum of other tissues. The changes of activity of enzymes involved in phospholipid biosynthesis during muscle development have been analysed. The extent of sn-glycero-3-phosphate and lysophosphatidylcholine acylation by acyl-CoA or free fatty acids in the presence of ATP and CoA is the same at every stage of development. The specific activity of glycerolphosphate acyltransferase(s) increases progressively during development up to about the 10th day of postnatal life and then decreases to the adult level. Linoleate esterifies sn-glycero-3-phosphate to a higher extent than palmitate, especially during postnatal period. The main product of sn-glycero-3-phosphate acylation is phosphatidic acid. The specific activity of lysolecithin acyltransferase increases from the embryonic period to a maximum between the 4th and the 9th day of postnatal life followed by a decrease to the adult value. the low embryonic value to a maximum at about the 3rd day of postnatal life, followed by a decrease to the adult value. The activity of cholinephosphotransferase decreases from a high value observed during the earliest embryonic period studied until the 3rd day before birth, and then begins to increase again from about the 5th day of postnatal life. The activity of ethanolaminephosphotransferase decreases continuously with age. The main product of phosphatidylethanolamine methylation is phosphatidylmonomethylethanolamine. The specific activity of phosphatidylethanolamine methyltransferase increases from", "contents": "Phospholipid biosynthesis in sarcoplasmic reticulum membrane during development. Biosynthesis of phosphatidic acid, phosphatidylcholine and phosphatidylethanolamine in the sarcoplasmic reticulum membrane has been investigated. The results show that sarcoplasmic reticulum, in addition to its main function, i.e. transport and accumulation of Ca2+, is able to synthetize phospholipids by the same pathways as endoplasmic reticulum of other tissues. The changes of activity of enzymes involved in phospholipid biosynthesis during muscle development have been analysed. The extent of sn-glycero-3-phosphate and lysophosphatidylcholine acylation by acyl-CoA or free fatty acids in the presence of ATP and CoA is the same at every stage of development. The specific activity of glycerolphosphate acyltransferase(s) increases progressively during development up to about the 10th day of postnatal life and then decreases to the adult level. Linoleate esterifies sn-glycero-3-phosphate to a higher extent than palmitate, especially during postnatal period. The main product of sn-glycero-3-phosphate acylation is phosphatidic acid. The specific activity of lysolecithin acyltransferase increases from the embryonic period to a maximum between the 4th and the 9th day of postnatal life followed by a decrease to the adult value. the low embryonic value to a maximum at about the 3rd day of postnatal life, followed by a decrease to the adult value. The activity of cholinephosphotransferase decreases from a high value observed during the earliest embryonic period studied until the 3rd day before birth, and then begins to increase again from about the 5th day of postnatal life. The activity of ethanolaminephosphotransferase decreases continuously with age. The main product of phosphatidylethanolamine methylation is phosphatidylmonomethylethanolamine. The specific activity of phosphatidylethanolamine methyltransferase increases from"} {"id": "PMID:182252", "title": "Partial purification and properties of diglyceride kinase from Escherichia coli.", "content": "Diglyceride kinase (diacylglycerol kinase, E.C. 2.7.1.-), an enzyme localized in the inner membrane of Escherichia coli, has been purified about 600-fold. The purified enzyme exhibits an absolute requirement for magnesium ion; its activity toward both lipid and nucleotide substrates is stimulated by diphosphatidylglycerol or other phospholipids. Adenine nucleotides are much better substrates for the enzyme than are other purine or pyrimidine nucleotides. The purified enzyme preparation catalyzes the phosphorylation of a number of lipids, including ceramide and several ceramide and diacylglycerol-like analogs. The broad lipid substrate specificity of diglyceride kinase suggests that this enzyme may function in vivo for the phosphorylation of an acceptor other than diacylglycerol.", "contents": "Partial purification and properties of diglyceride kinase from Escherichia coli. Diglyceride kinase (diacylglycerol kinase, E.C. 2.7.1.-), an enzyme localized in the inner membrane of Escherichia coli, has been purified about 600-fold. The purified enzyme exhibits an absolute requirement for magnesium ion; its activity toward both lipid and nucleotide substrates is stimulated by diphosphatidylglycerol or other phospholipids. Adenine nucleotides are much better substrates for the enzyme than are other purine or pyrimidine nucleotides. The purified enzyme preparation catalyzes the phosphorylation of a number of lipids, including ceramide and several ceramide and diacylglycerol-like analogs. The broad lipid substrate specificity of diglyceride kinase suggests that this enzyme may function in vivo for the phosphorylation of an acceptor other than diacylglycerol."} {"id": "PMID:182253", "title": "Abnormal membrane phospholipid content in subcellular fractions from the Morris 7777 hepatoma.", "content": "1. Mitochondrial and microsomal fractions were prepared from normal rat liver and the Morris 7777 hepatoma and characterized by the use of the marker enzymes, succinate dehydrogenase and rotenone-insensitive NADPH-cytochrome c reductase. 2. The phospholipid content per mg membrane protein of Morris 7777 hepatoma mitochondria was increased by 75% as compared with mitochondria from normal rat liver. Microsomes from this poorly-differentiated tumor were found to have a 45% decrease in the content of phospholipid. These abnormalities were independent of tumor size or age. 3. The percent phospholipid content of the subcellular fractions was determined, and revealed an increase in the percent sphingomyelin in both the microsomal and mitochondrial fractions of the tumor. Decreases in the percent phosphatidylcholine and phosphatidylethanolamine were noted in tumor microsomes as compared with normal liver. Diphosphatidylglycerol was not found in significant quantities in the microsomal fraction of this hepatoma line. 4. The content of the various phospholipid classes per mg protein in the respective mitochondrial and microsomal fractions was determined. Large increases in nearly all the major phospholipid classes were found in tumor mitochondria; tumor microsomes were characterized by an increased content of sphingomyelin but the content of nearly all other phospholipids was significantly decreased. These findings suggest the presence of disturbances in the regulation of phospholipid metabolism in subcellular organelle membranes of the Morris 7777 hepatoma.", "contents": "Abnormal membrane phospholipid content in subcellular fractions from the Morris 7777 hepatoma. 1. Mitochondrial and microsomal fractions were prepared from normal rat liver and the Morris 7777 hepatoma and characterized by the use of the marker enzymes, succinate dehydrogenase and rotenone-insensitive NADPH-cytochrome c reductase. 2. The phospholipid content per mg membrane protein of Morris 7777 hepatoma mitochondria was increased by 75% as compared with mitochondria from normal rat liver. Microsomes from this poorly-differentiated tumor were found to have a 45% decrease in the content of phospholipid. These abnormalities were independent of tumor size or age. 3. The percent phospholipid content of the subcellular fractions was determined, and revealed an increase in the percent sphingomyelin in both the microsomal and mitochondrial fractions of the tumor. Decreases in the percent phosphatidylcholine and phosphatidylethanolamine were noted in tumor microsomes as compared with normal liver. Diphosphatidylglycerol was not found in significant quantities in the microsomal fraction of this hepatoma line. 4. The content of the various phospholipid classes per mg protein in the respective mitochondrial and microsomal fractions was determined. Large increases in nearly all the major phospholipid classes were found in tumor mitochondria; tumor microsomes were characterized by an increased content of sphingomyelin but the content of nearly all other phospholipids was significantly decreased. These findings suggest the presence of disturbances in the regulation of phospholipid metabolism in subcellular organelle membranes of the Morris 7777 hepatoma."} {"id": "PMID:182254", "title": "Molecular weight of Yaba monkey tumor virus DNA.", "content": "The molecular weight of Yaba virus DNA was determined by the isolation of intact DNA genomes from Yaba virus, which had been purified by two sucrose density gradient and one potassium tartrate gradient centrifugations, by cosedimentation with T2 DNA. The molecular weight of Yaba DNA was calculated to be 119 - 10(6).", "contents": "Molecular weight of Yaba monkey tumor virus DNA. The molecular weight of Yaba virus DNA was determined by the isolation of intact DNA genomes from Yaba virus, which had been purified by two sucrose density gradient and one potassium tartrate gradient centrifugations, by cosedimentation with T2 DNA. The molecular weight of Yaba DNA was calculated to be 119 - 10(6)."} {"id": "PMID:182255", "title": "Repair of x-ray-induced single strand breaks in toluenized Escherichia coli cells.", "content": "We have used sedimentation in alkali to estimate the repair of X-ray-induced single strand breaks in the DNA of irradiated toluenized Escherichia coli cells. Extensive repair requires no exogenous cofactors except ATP although other individual NTPs (except U) or dNTPs can substitute for ATP. There is no repair in polA or resA cells and since nicotinamide mononucleotide (NMN) inhibits repair in wild type cells we interpret the results as indicating that both ligase and polymerase I are needed for repair but that the amount of any gap filling is small and extensive repair replication is not necessary.", "contents": "Repair of x-ray-induced single strand breaks in toluenized Escherichia coli cells. We have used sedimentation in alkali to estimate the repair of X-ray-induced single strand breaks in the DNA of irradiated toluenized Escherichia coli cells. Extensive repair requires no exogenous cofactors except ATP although other individual NTPs (except U) or dNTPs can substitute for ATP. There is no repair in polA or resA cells and since nicotinamide mononucleotide (NMN) inhibits repair in wild type cells we interpret the results as indicating that both ligase and polymerase I are needed for repair but that the amount of any gap filling is small and extensive repair replication is not necessary."} {"id": "PMID:182256", "title": "The ATP dependence of the incision and resynthesis steps of excision repair.", "content": "Escherichia coli made permeable by treatment with toluene can perform a mode of DNA synthesis that is stimulated by ultraviolet radiation and closely resembles the resynthesis step of excision repair. If ultraviolet-irradiated toulene-treated cells are incubated in an assay mixture with ATP but without the four deoxyribonucleoside triphosphates (dNTPs) or NAD, accumulations of single-strand breaks in the DNA are detected by alkaline sucrose gradient analysis. A second incubation with the dNTP'S and NAD but without ATP produces nonconservative DNA synthesis in strains with normal levels of DNA polymerase I. However, in PolA strains, ATP must be present during the second incubation in order to produce measurable amounts of ultraviolet-stimulated DNA synthesis. These results suggest that in strains deficient in DNA polymerase I there may be two ATP-dependent steps in this repair pathway, one required for incision and one associated with resynthesis.", "contents": "The ATP dependence of the incision and resynthesis steps of excision repair. Escherichia coli made permeable by treatment with toluene can perform a mode of DNA synthesis that is stimulated by ultraviolet radiation and closely resembles the resynthesis step of excision repair. If ultraviolet-irradiated toulene-treated cells are incubated in an assay mixture with ATP but without the four deoxyribonucleoside triphosphates (dNTPs) or NAD, accumulations of single-strand breaks in the DNA are detected by alkaline sucrose gradient analysis. A second incubation with the dNTP'S and NAD but without ATP produces nonconservative DNA synthesis in strains with normal levels of DNA polymerase I. However, in PolA strains, ATP must be present during the second incubation in order to produce measurable amounts of ultraviolet-stimulated DNA synthesis. These results suggest that in strains deficient in DNA polymerase I there may be two ATP-dependent steps in this repair pathway, one required for incision and one associated with resynthesis."} {"id": "PMID:182257", "title": "The restriction endonucleases in Bacillus amyloliquefaciens N strain. Substrate specificities.", "content": "Two species of restriction endonuclease were isolated by gel filtration and DEAE-cellulose chromatography from a cell-free extract of Bacillus amyloliquefaciens (B. subtilits) N strain; a lower molecular weight endonuclease (endonuclease R.BamNI) and a higher molecular-weight one (endonuclease R.BamNx). Both of them required only Mg2+ for their activities. Endonuclease R.BamNx introduced a larger number of site-specific scissions in Excherchia coli phage lambda DNA that endonuclease R.BamNI did. Endonuclease R.BamNx cleaved Bacillus phage phi 105C DNA at the specific sites which are classified into two groups: one type of sites is modified by B. amyloliquefaciens H strain in vivo while the other is not affected. It was also active on DNA'S OF E. coli phage T7, lambdadvl, Simian virus 40 (SV40) and colicinogenic factor ColEI and was inactive on DNAs of Bacillus phages phi 29 and M2. Endonuclease R.BamHI isolated from H strain by Wilson and Young. This endonuclease was active on DNAs of phage lambda, lambdadvl and SV40, adn was inactive on DNAs of phages phi 105C, phi 29, M2 and T7, and ColEI DNA.", "contents": "The restriction endonucleases in Bacillus amyloliquefaciens N strain. Substrate specificities. Two species of restriction endonuclease were isolated by gel filtration and DEAE-cellulose chromatography from a cell-free extract of Bacillus amyloliquefaciens (B. subtilits) N strain; a lower molecular weight endonuclease (endonuclease R.BamNI) and a higher molecular-weight one (endonuclease R.BamNx). Both of them required only Mg2+ for their activities. Endonuclease R.BamNx introduced a larger number of site-specific scissions in Excherchia coli phage lambda DNA that endonuclease R.BamNI did. Endonuclease R.BamNx cleaved Bacillus phage phi 105C DNA at the specific sites which are classified into two groups: one type of sites is modified by B. amyloliquefaciens H strain in vivo while the other is not affected. It was also active on DNA'S OF E. coli phage T7, lambdadvl, Simian virus 40 (SV40) and colicinogenic factor ColEI and was inactive on DNAs of Bacillus phages phi 29 and M2. Endonuclease R.BamHI isolated from H strain by Wilson and Young. This endonuclease was active on DNAs of phage lambda, lambdadvl and SV40, adn was inactive on DNAs of phages phi 105C, phi 29, M2 and T7, and ColEI DNA."} {"id": "PMID:182258", "title": "Further purification and characterization of T4 endonuclease V.", "content": "T4 endonuclease V, which is involved in repair of ultraviolet-damaged DNA, has been purified 3600 fold from T4D-infected Escherichia coli. The enzyme shows optimal activity at pH 7.2 and does not require added divalent ions. Endonuclease V attacks both native and heat-denatured DNA provided that the DNA has been irradiated, and the enzyme activity is dependent on the dose of ultraviolet irradiation. The rate and the extent of the reaction are greater with irradiated native DNA although the Km values for the two types of DNA are the same (2.25 - 10(-5) M). The enzyme is readily inactivated by heat and is sensitive to p-chloromercuribenzoate. Endonuclease V-treated irradiated DNA is degraded by spleen phosphodiesterase only when the DNA has been treated with alkaline phosphatase, suggesting that the enzyme produces 5'-phosphoryl termini.", "contents": "Further purification and characterization of T4 endonuclease V. T4 endonuclease V, which is involved in repair of ultraviolet-damaged DNA, has been purified 3600 fold from T4D-infected Escherichia coli. The enzyme shows optimal activity at pH 7.2 and does not require added divalent ions. Endonuclease V attacks both native and heat-denatured DNA provided that the DNA has been irradiated, and the enzyme activity is dependent on the dose of ultraviolet irradiation. The rate and the extent of the reaction are greater with irradiated native DNA although the Km values for the two types of DNA are the same (2.25 - 10(-5) M). The enzyme is readily inactivated by heat and is sensitive to p-chloromercuribenzoate. Endonuclease V-treated irradiated DNA is degraded by spleen phosphodiesterase only when the DNA has been treated with alkaline phosphatase, suggesting that the enzyme produces 5'-phosphoryl termini."} {"id": "PMID:182259", "title": "Repair of DNA damaged by methyl methanesulfonate in bacteriophage T4.", "content": "A highly purified preparation of T4 endonuclease V does not degrade DNA alkylated with methyl methanesulfonate, and the methyl methanesulfonate sensitivity of T4 wild type and x mutant is not affected by the v mutation. Thus, T4 endonuclease V, the v gene product, does not seem to be involved in a repair or an abortive repair of methyl methanesulfonate-damaged T4 DNA. The x and y genes of T4 and the polA and the uvrD genes of Escherichia coli are concerned with the repair of methyl methanesulfonate-induced damages in T4 DNA. Since effects of the polA and the x or y mutations are additive, it is supposed that there are at least two pathways for the repair of methyl meth-anesulfonate-damaged T4 DNA, one controlled by the x and the y genes and the other in which E. coli DNA olymerase I is involved. The partial suppression of the x gene mutation at high temerature was also demonstrated.", "contents": "Repair of DNA damaged by methyl methanesulfonate in bacteriophage T4. A highly purified preparation of T4 endonuclease V does not degrade DNA alkylated with methyl methanesulfonate, and the methyl methanesulfonate sensitivity of T4 wild type and x mutant is not affected by the v mutation. Thus, T4 endonuclease V, the v gene product, does not seem to be involved in a repair or an abortive repair of methyl methanesulfonate-damaged T4 DNA. The x and y genes of T4 and the polA and the uvrD genes of Escherichia coli are concerned with the repair of methyl methanesulfonate-induced damages in T4 DNA. Since effects of the polA and the x or y mutations are additive, it is supposed that there are at least two pathways for the repair of methyl meth-anesulfonate-damaged T4 DNA, one controlled by the x and the y genes and the other in which E. coli DNA olymerase I is involved. The partial suppression of the x gene mutation at high temerature was also demonstrated."} {"id": "PMID:182260", "title": "Lateral diffusion, order parameter and phase transition in phospholipid bilayer membranes containing tocopheryl acetate.", "content": "Lateral diffusion coefficient and order parameter measurements were made with pyrene excimer optical probes and fatty acid spin label probes respectively in pure dipalmitoyl phosphatidylcholine membranes and in membranes doped with tocopheryl acetate. The investigation shows, that the lateral diffusion coefficient for pyrene in dipalmitoyl pholphatidylcholine membranes is decreased whereas the order parameter of the fatty acid chains is slightly increased in the inner part of the membranes by the addition of tocopheryl acetate. The fluid-solid equilibrium phase diagram of dipalmitoyl phosphatidylcholine/tocopheryl acetate mixed membranes has been constructed from the measurements of the partition of (2,2,6,6-tetramethylpiperdine-1-oxyl) TEMPO spin labels between lipid and aqueous regions as function of temperature. In the membranes tocopheryl acetate induces a strong broadening of the temperature range of the phase transition. At low tocopheryl acetate concentrations dipalmitoyl phosphatidylcholine and tocopheryl acetate seem to be completely miscible in the solid and in the liquid crystalline state.", "contents": "Lateral diffusion, order parameter and phase transition in phospholipid bilayer membranes containing tocopheryl acetate. Lateral diffusion coefficient and order parameter measurements were made with pyrene excimer optical probes and fatty acid spin label probes respectively in pure dipalmitoyl phosphatidylcholine membranes and in membranes doped with tocopheryl acetate. The investigation shows, that the lateral diffusion coefficient for pyrene in dipalmitoyl pholphatidylcholine membranes is decreased whereas the order parameter of the fatty acid chains is slightly increased in the inner part of the membranes by the addition of tocopheryl acetate. The fluid-solid equilibrium phase diagram of dipalmitoyl phosphatidylcholine/tocopheryl acetate mixed membranes has been constructed from the measurements of the partition of (2,2,6,6-tetramethylpiperdine-1-oxyl) TEMPO spin labels between lipid and aqueous regions as function of temperature. In the membranes tocopheryl acetate induces a strong broadening of the temperature range of the phase transition. At low tocopheryl acetate concentrations dipalmitoyl phosphatidylcholine and tocopheryl acetate seem to be completely miscible in the solid and in the liquid crystalline state."} {"id": "PMID:182261", "title": "Properties of spin labelled membranes of Fusarium oxysporum f. sp. lycopersici.", "content": "Growth temperature-induced compositional changes in membranes of Fusarium oxysporum provided a test system for study of the relationship between physical properties and composition. Growth at 15 degrees C was characterized by a decrease in phospholipid content relative to sterol content, a shift in phospholipid composition from phosphatidylcholine to phosphatidylethanolamine and a marked enhancement in the amount of polyunsaturated fatty acids in the phospholipid and triglyceride classes. Uptake of a spin labelled analog of stearic acid during growth and subsequent solution of the probe in the membranes allowed estimation of viscosity and molecular order of the membranes of live cells and of isolated membrane preparations. Less than 1/20 of the intracellular label was accessible to sodium ascorbate while none was released by sodium dodecyl sulfate. All of the label in live cells was reduced by in vivo respiratory activity above 20 degrees C but this process could be reversed or avoided by added ferricyanide. A cholestane spin probe was also incorporated into the membranes. The probes were not reduced as readily in isolated membranes and hence fluidity of the membranes could be assessed over a wide temperature range. At low temperatures (-10 degrees C) a nonlethal, liquid-solid phase transition was indicated in isolated membrane lipids while at higher (lethal) temperatures (40-45 degrees C), discontinuities appeared in Arrhenius plots of rotational correlation time. Activation energies for isotropic rotation of the stearate probes in the membranes changed markedly in this temperature range and this effect correlated closely with loss of viability of conidial cells. Correlation times for stearate probes showed little variation with growth temperature nor were any breaks in Arrhenius plots of this parameter detected in the range 0-35 degrees C in whole cells or isolated membranes. The data indicated control of membrane physical properties within close tolerances throughout the physiological temperature range regardless of growth temperature. It was concluded that this homeostatic phenomenon was due to the counteractive effects of sterol/phospholipid ratio, phospholipid composition and fatty acid polyunsaturation since the condensing and fluidizing components of the isolated total membranes vary in a reciprocal manner.", "contents": "Properties of spin labelled membranes of Fusarium oxysporum f. sp. lycopersici. Growth temperature-induced compositional changes in membranes of Fusarium oxysporum provided a test system for study of the relationship between physical properties and composition. Growth at 15 degrees C was characterized by a decrease in phospholipid content relative to sterol content, a shift in phospholipid composition from phosphatidylcholine to phosphatidylethanolamine and a marked enhancement in the amount of polyunsaturated fatty acids in the phospholipid and triglyceride classes. Uptake of a spin labelled analog of stearic acid during growth and subsequent solution of the probe in the membranes allowed estimation of viscosity and molecular order of the membranes of live cells and of isolated membrane preparations. Less than 1/20 of the intracellular label was accessible to sodium ascorbate while none was released by sodium dodecyl sulfate. All of the label in live cells was reduced by in vivo respiratory activity above 20 degrees C but this process could be reversed or avoided by added ferricyanide. A cholestane spin probe was also incorporated into the membranes. The probes were not reduced as readily in isolated membranes and hence fluidity of the membranes could be assessed over a wide temperature range. At low temperatures (-10 degrees C) a nonlethal, liquid-solid phase transition was indicated in isolated membrane lipids while at higher (lethal) temperatures (40-45 degrees C), discontinuities appeared in Arrhenius plots of rotational correlation time. Activation energies for isotropic rotation of the stearate probes in the membranes changed markedly in this temperature range and this effect correlated closely with loss of viability of conidial cells. Correlation times for stearate probes showed little variation with growth temperature nor were any breaks in Arrhenius plots of this parameter detected in the range 0-35 degrees C in whole cells or isolated membranes. The data indicated control of membrane physical properties within close tolerances throughout the physiological temperature range regardless of growth temperature. It was concluded that this homeostatic phenomenon was due to the counteractive effects of sterol/phospholipid ratio, phospholipid composition and fatty acid polyunsaturation since the condensing and fluidizing components of the isolated total membranes vary in a reciprocal manner."} {"id": "PMID:182262", "title": "The insulin receptor of the turkey erythrocyte. Characterization of the membrane-bound receptor.", "content": "The insulin receptor of the turkey erythrocyte has previously been shown to be very similar to that of the mammalian insulin receptors. As a first step in the isolation of this receptor a highly purified plasma membrane fraction has been prepared. The binding characteristics of the purified membrane-bound receptor were identical to those found with intact erythrocytes, but the membrane preparation had very little insulin-degrading activity. Isolation of the membrane by the methods described gave a 100-fold purification of the insulin receptor with 67% yield.", "contents": "The insulin receptor of the turkey erythrocyte. Characterization of the membrane-bound receptor. The insulin receptor of the turkey erythrocyte has previously been shown to be very similar to that of the mammalian insulin receptors. As a first step in the isolation of this receptor a highly purified plasma membrane fraction has been prepared. The binding characteristics of the purified membrane-bound receptor were identical to those found with intact erythrocytes, but the membrane preparation had very little insulin-degrading activity. Isolation of the membrane by the methods described gave a 100-fold purification of the insulin receptor with 67% yield."} {"id": "PMID:182263", "title": "Interaction of steptolysin O with sterols.", "content": "A quantitative study of the specific inhibitory power of cholesterol and other sterols on the hemolytic properties of streptolysin O is reported. This streptococcal exocellular protein is a cytolytic toxin which disrupts cytoplasmic membranes of eukaryote cells. The structural characteristics, particularly the stereochemical ones required for a steroid molecule to inhibit the cytolytic activity of streptolysin O, have been investigated in detail. By immunodiffusion techniques, in agar gel plates or tubes containing sterols, the formation of hydrophobic complexes between streptolysin O and inhibitory steroids, but not non-inhibitory steroids except lanosterol, is shown. Upon interaction with inhibitory steroids streptolysin O loses its immunoreactive properties towards neutralizing and precipitating homologous antibodies. An interpretation of the mechanism of biomembrane disorganization by streptolysin O is discussed in the light of its steroid binding properties.", "contents": "Interaction of steptolysin O with sterols. A quantitative study of the specific inhibitory power of cholesterol and other sterols on the hemolytic properties of streptolysin O is reported. This streptococcal exocellular protein is a cytolytic toxin which disrupts cytoplasmic membranes of eukaryote cells. The structural characteristics, particularly the stereochemical ones required for a steroid molecule to inhibit the cytolytic activity of streptolysin O, have been investigated in detail. By immunodiffusion techniques, in agar gel plates or tubes containing sterols, the formation of hydrophobic complexes between streptolysin O and inhibitory steroids, but not non-inhibitory steroids except lanosterol, is shown. Upon interaction with inhibitory steroids streptolysin O loses its immunoreactive properties towards neutralizing and precipitating homologous antibodies. An interpretation of the mechanism of biomembrane disorganization by streptolysin O is discussed in the light of its steroid binding properties."} {"id": "PMID:182264", "title": "Fucolipid metabolism as a function of cell population density in normal and murine sarcoma virus-transformed rat cells.", "content": "The incorporation of isotopically labeled fucose into the lipids of normal and murine sarcoma virus-transformed rat cells as a function of cell population density was examined. When normal cells were seeded at low cell density, the levels of the major fucolipids, i.e., fucolipids III and IV, were substantially reduced, but then they increased as the cells approached confluency. This variation in synthesis of fucolipids III and IV appeared to be primarily related to cell density and not to cell growth. Chase experiments revealed that the reduced level of fucolipids III and IV in sparse normal cells is due to decreased synthesis rather than to increased catabolism. In contrast to the observations with normal rat cells, the high level of fucolipid III and the low level of fucolipid IV in murine sarcoma virus-transformed rat cells was shown to be independent of cell population density.", "contents": "Fucolipid metabolism as a function of cell population density in normal and murine sarcoma virus-transformed rat cells. The incorporation of isotopically labeled fucose into the lipids of normal and murine sarcoma virus-transformed rat cells as a function of cell population density was examined. When normal cells were seeded at low cell density, the levels of the major fucolipids, i.e., fucolipids III and IV, were substantially reduced, but then they increased as the cells approached confluency. This variation in synthesis of fucolipids III and IV appeared to be primarily related to cell density and not to cell growth. Chase experiments revealed that the reduced level of fucolipids III and IV in sparse normal cells is due to decreased synthesis rather than to increased catabolism. In contrast to the observations with normal rat cells, the high level of fucolipid III and the low level of fucolipid IV in murine sarcoma virus-transformed rat cells was shown to be independent of cell population density."} {"id": "PMID:182265", "title": "Regulation of ovarian steroidogenesis. The disparity between 125I-labelled choriogonadotropin binding cyclic adenosine 3',5'-monophosphate formation and progesterone synthesis in the rat ovary.", "content": "The binding of 125I-labelled human choriogonadotropin, formation of cyclic adenosine 3',5'-monophosphate (cyclic AMP), and synthesis of progesterone were examined in ovarian cells from immature rats. Collagenase dispersed ovarian cells were found to respond specifically to lutropin-like activity. The equilibrium dissociation constant (Kd) for the binding of 125I-for the binding of 125I-labelled choriogonadotropin was 1.7-10(-10) M. Progesterone synthesis was increased at least 40-fold and cyclic AMP formation 10-fold in response to maximum hormonal stimulation. The concentration of choriogonadotropin which stimulated progesterone synthesis maximally in Eagle's minimum essential medium--0.1% gelatin (2 ng/ml), resulted in minimal (less than 30% of maximum) increases in cyclic AMP accumulation and hormone binding. Similarly, binding of choriogonadotropin was not saturated at a hormone concentration (50 ng/ml) that stimulated maximal cyclic AMP formation. These results are consistent with the existence of receptor reserve in the ovarian cell. A marked shift in the dose vs. response relationship for progesterone synthesis occurred when fetal calf serum was used to supplement Eagle's minimum essential medium, however. Under these experimental conditions, progesterone synthesis reached a maximum at a hormone concentration of the same order of magnitude as did cyclic AMP formation. It is concluded that the degree of spare receptor effect observed may depend not only on an absolute amount of excess receptor, but also on the readiness of the system to respond in a given fashion.", "contents": "Regulation of ovarian steroidogenesis. The disparity between 125I-labelled choriogonadotropin binding cyclic adenosine 3',5'-monophosphate formation and progesterone synthesis in the rat ovary. The binding of 125I-labelled human choriogonadotropin, formation of cyclic adenosine 3',5'-monophosphate (cyclic AMP), and synthesis of progesterone were examined in ovarian cells from immature rats. Collagenase dispersed ovarian cells were found to respond specifically to lutropin-like activity. The equilibrium dissociation constant (Kd) for the binding of 125I-for the binding of 125I-labelled choriogonadotropin was 1.7-10(-10) M. Progesterone synthesis was increased at least 40-fold and cyclic AMP formation 10-fold in response to maximum hormonal stimulation. The concentration of choriogonadotropin which stimulated progesterone synthesis maximally in Eagle's minimum essential medium--0.1% gelatin (2 ng/ml), resulted in minimal (less than 30% of maximum) increases in cyclic AMP accumulation and hormone binding. Similarly, binding of choriogonadotropin was not saturated at a hormone concentration (50 ng/ml) that stimulated maximal cyclic AMP formation. These results are consistent with the existence of receptor reserve in the ovarian cell. A marked shift in the dose vs. response relationship for progesterone synthesis occurred when fetal calf serum was used to supplement Eagle's minimum essential medium, however. Under these experimental conditions, progesterone synthesis reached a maximum at a hormone concentration of the same order of magnitude as did cyclic AMP formation. It is concluded that the degree of spare receptor effect observed may depend not only on an absolute amount of excess receptor, but also on the readiness of the system to respond in a given fashion."} {"id": "PMID:182266", "title": "Materials released into culture medium by normal and oncogenic virus-transformed mammalian cells.", "content": "Materials released into culture medium by transformed and untransformed baby hamster kidney cells labelled with glucosamine, sulfate, fucose or leucine were characterized. Some of the components could also be labelled by iodination of intact cells, indicating their surface origin. Analysis on gradient polyacrylamide sodium lauryl sulfate gels demonstrated that a group of high apparent molecular weight glucosamine-labelled components were more abundant in materials released from Rous sarcoma virus-transformed baby hamster kidney cells than from baby hamster kidney cells or polyoma virus-transformed baby hamster kidney cells. The relative rates of release of glucosamine-labelled components from transformed and untransformed cells were similar except that the transformed baby hamster kidney cells released some large molecular weight components slightly more rapidly than baby hamster kidney cells. Treatment of labelled medium materials with testicular hyaluronidase removed much glucosamine label from the materials but did not affect the amounts of other labels. After treatment with hyaluronidase, the patterns of labelled conditioned media from both transformed and untransformed baby hamster kidney cells were qualitatively and quantitatively very similar, suggesting that the differences seen in untreated labelled conditioned media were due to the presence of hyaluronidase-sensitive materials associated with medium materials rather than to actual differences in glycoproteins.", "contents": "Materials released into culture medium by normal and oncogenic virus-transformed mammalian cells. Materials released into culture medium by transformed and untransformed baby hamster kidney cells labelled with glucosamine, sulfate, fucose or leucine were characterized. Some of the components could also be labelled by iodination of intact cells, indicating their surface origin. Analysis on gradient polyacrylamide sodium lauryl sulfate gels demonstrated that a group of high apparent molecular weight glucosamine-labelled components were more abundant in materials released from Rous sarcoma virus-transformed baby hamster kidney cells than from baby hamster kidney cells or polyoma virus-transformed baby hamster kidney cells. The relative rates of release of glucosamine-labelled components from transformed and untransformed cells were similar except that the transformed baby hamster kidney cells released some large molecular weight components slightly more rapidly than baby hamster kidney cells. Treatment of labelled medium materials with testicular hyaluronidase removed much glucosamine label from the materials but did not affect the amounts of other labels. After treatment with hyaluronidase, the patterns of labelled conditioned media from both transformed and untransformed baby hamster kidney cells were qualitatively and quantitatively very similar, suggesting that the differences seen in untreated labelled conditioned media were due to the presence of hyaluronidase-sensitive materials associated with medium materials rather than to actual differences in glycoproteins."} {"id": "PMID:182267", "title": "Analysis of the electron paramagnetic resonance spectrum of the cobalamin intermediate in ribonucleotide reduction.", "content": "EPR absorption-derivative lineshapes have been computed and least-squares fitted to the spectrum of the intermediate derived from 5'-deoxy-5'-adenosylcobalamin in the ribonucleotide reductase reaction. A Gaussian-type intrinsic lineshape was assumed and the effects of inhomogenous broadening, rotation of coordinate axes of the A-tensor relative to the g-tensor, angular dependence of transition probability and ligand hyperfine splitting have also been investigated. When the overall spectrum was computed as the sum of the lineshapes corresponding to two distinct Co(II) species, A and B, each having rhombic symmetry, the least squares procedure converged to a much better fit than with a single species, and matched almost all of the features of the experimental spectrum. The magnetic properties of A and B were compared with those of a series of other Co(II) complexes by a plot of g - g versus A - A. The results eliminate cobalt with 5-coordination to nitrogen for A and B, and suggest low-spin cobalt complexes having strongly distorted 6-fold coordination. The possibility that the sixth, symmetry-decreasing ligand is the oxygen molecule is excluded by the chemistry of the system and by the EPR properties of previously reported cob(II)alamins. It is suggested that the sixth ligand is a carbonyl, amide or sulfhydryl group of an enzyme sidechain which is inserted off-axis into the coordination position so as to exert the observed symmetry-lowering effect.", "contents": "Analysis of the electron paramagnetic resonance spectrum of the cobalamin intermediate in ribonucleotide reduction. EPR absorption-derivative lineshapes have been computed and least-squares fitted to the spectrum of the intermediate derived from 5'-deoxy-5'-adenosylcobalamin in the ribonucleotide reductase reaction. A Gaussian-type intrinsic lineshape was assumed and the effects of inhomogenous broadening, rotation of coordinate axes of the A-tensor relative to the g-tensor, angular dependence of transition probability and ligand hyperfine splitting have also been investigated. When the overall spectrum was computed as the sum of the lineshapes corresponding to two distinct Co(II) species, A and B, each having rhombic symmetry, the least squares procedure converged to a much better fit than with a single species, and matched almost all of the features of the experimental spectrum. The magnetic properties of A and B were compared with those of a series of other Co(II) complexes by a plot of g - g versus A - A. The results eliminate cobalt with 5-coordination to nitrogen for A and B, and suggest low-spin cobalt complexes having strongly distorted 6-fold coordination. The possibility that the sixth, symmetry-decreasing ligand is the oxygen molecule is excluded by the chemistry of the system and by the EPR properties of previously reported cob(II)alamins. It is suggested that the sixth ligand is a carbonyl, amide or sulfhydryl group of an enzyme sidechain which is inserted off-axis into the coordination position so as to exert the observed symmetry-lowering effect."} {"id": "PMID:182268", "title": "Simultaneous selection of mutants in gluconeogenesis and nucleoside catabolism in Salmonella typhimurium.", "content": "Penicillin selection in minimal thymidine medium, used to select mutants in deoxynucleoside catabolism, also yields a high percentage (37%) of mutants in fructose diphosphatase. The expression of the deo regulon is retarded in the mutants defective in the glyconeogenic pathway.", "contents": "Simultaneous selection of mutants in gluconeogenesis and nucleoside catabolism in Salmonella typhimurium. Penicillin selection in minimal thymidine medium, used to select mutants in deoxynucleoside catabolism, also yields a high percentage (37%) of mutants in fructose diphosphatase. The expression of the deo regulon is retarded in the mutants defective in the glyconeogenic pathway."} {"id": "PMID:182269", "title": "On the role of the collagen carbohydrate residues in the platelet. Collagen interaction.", "content": "It has been proposed that the platelet : collagen interaction is mediated in part by the collagen carbohydrate residues. To test this hypothesis we have oxidized monomeric and polymeric collagen with sodium periodate under conditions specifically designed to minimize destruction of periodate-susceptible bonds other than in the carbohydrate residues. Oxidation of the collagen significantly reduced its ability to interact with platelets. The extent of inhibition paralleled the extent of carbohydrate destruction. Oxidation with periodate also delayed the polymerization of the monomeric collagen, but even after polymerization the oxidized collagen failed to initiate the release reaction. These observations suggest that the collagen carbohydrate residues may be either near to or part of the site(s) on the collagen molecule required for platelet adhesion.", "contents": "On the role of the collagen carbohydrate residues in the platelet. Collagen interaction. It has been proposed that the platelet : collagen interaction is mediated in part by the collagen carbohydrate residues. To test this hypothesis we have oxidized monomeric and polymeric collagen with sodium periodate under conditions specifically designed to minimize destruction of periodate-susceptible bonds other than in the carbohydrate residues. Oxidation of the collagen significantly reduced its ability to interact with platelets. The extent of inhibition paralleled the extent of carbohydrate destruction. Oxidation with periodate also delayed the polymerization of the monomeric collagen, but even after polymerization the oxidized collagen failed to initiate the release reaction. These observations suggest that the collagen carbohydrate residues may be either near to or part of the site(s) on the collagen molecule required for platelet adhesion."} {"id": "PMID:182270", "title": "Purification, characteristics and sequence of a peptide containing an essential lysine residue.", "content": "Glutamate dehydrogenase (EC 1.4.1.2-4) has been purified and crystallized from the acetone powder of tuna liver. The enzyme has a molecular weight of 333 000 +/- 15 000 as evaluated by sedimentation equilibrium and constists of six identical subunits. Unlike the bovine enzyme the molecular weight does not increase with increasing protein concentration indicating that the tuna enzyme has no tendency to polymerize. The amino acid composition and peptide maps of the tuna and bovine liver enzyme are similar, suggesting considerable homology between the two enzymes. Furthermore, from the tryptic digest a hexadecapeptide containing a lysine residue reactive to pyridoxal 5'-phosphate exhibits the same composition and sequence as the peptide containing the reactive lysine-126 in the sequence of the bovine enzyme. The molecular activity is 25 and 510 mol of substrate per mol enzyme per s, respectively, for the glutamate oxidation and the alpha-ketoglutarate reduction with NAD or NADP as coenzymes. The enzyme is regulated by pyridine nucleotides like other vertebrate enzymes, but it also exhibits some coenzyme specificity, the activity being about fifteen times higher with NAD than with NADP.", "contents": "Purification, characteristics and sequence of a peptide containing an essential lysine residue. Glutamate dehydrogenase (EC 1.4.1.2-4) has been purified and crystallized from the acetone powder of tuna liver. The enzyme has a molecular weight of 333 000 +/- 15 000 as evaluated by sedimentation equilibrium and constists of six identical subunits. Unlike the bovine enzyme the molecular weight does not increase with increasing protein concentration indicating that the tuna enzyme has no tendency to polymerize. The amino acid composition and peptide maps of the tuna and bovine liver enzyme are similar, suggesting considerable homology between the two enzymes. Furthermore, from the tryptic digest a hexadecapeptide containing a lysine residue reactive to pyridoxal 5'-phosphate exhibits the same composition and sequence as the peptide containing the reactive lysine-126 in the sequence of the bovine enzyme. The molecular activity is 25 and 510 mol of substrate per mol enzyme per s, respectively, for the glutamate oxidation and the alpha-ketoglutarate reduction with NAD or NADP as coenzymes. The enzyme is regulated by pyridine nucleotides like other vertebrate enzymes, but it also exhibits some coenzyme specificity, the activity being about fifteen times higher with NAD than with NADP."} {"id": "PMID:182271", "title": "Regulation of synthase phosphatase and phosphorylase phosphatase in rat liver.", "content": "Using substrates purified from liver, the apparent Km values of synthase phosphatase ([UDPglucose--glycogen glucosyltransferase-D]phosphohydrolase, EC 3.1.3.42) and phosphorylase phosphatase (phosphorylase a phosphohydrolase, EC 3.1.3.17) were found to be 0.7 and 60 units/ml respectively. The maximal velocity of phosphorylase phosphatase was more than a 100 times that of synthase phosphatase. In adrenalectomized, fasted animals there was a complete loss of synthase phosphatase but only a slight decrease in phosphorylase phosphatase when activity was measured using endogenous substrates in a concentrated liver extract. When assayed under optimal conditions with purified substrates, both activities were present but had decreased to very low levels. Mixing experiments indicated that synthase D present in the extract of adrenalectomized fasted animals was altered such that it was no longer a substrate for synthase phosphatase from normal rats. Phosphorylase a substrate on the other hand was unaltered and readily converted. When glucose was given in vivo, no change in percent of synthase in the I form was seen in adrenalectomized rats but the percent of phosphorylase in the a form was reduced. Precipitation of protein from an extract of normal fed rats with ethanol produced a large activation of phosphorylase phosphatase activity with no corresponding increase in synthase phosphatase activity. Despite the low phosphorylase phosphatase present in extracts of adrenalectomized fasted animals, ethanol precipitation increased activity to the same high level as obtained in the normal fed rats. Synthase phosphatase and phosphorylase phosphatase activities were also decreased in normal fasted, diabetic fed and fasted, and adrenalectomized fed rats. Both enzymes recovered in the same manner temporally after oral glucose administration to adrenalectomized, fasted rats. These results suggest an integrated regulatory mechanism for the two phosphatase.", "contents": "Regulation of synthase phosphatase and phosphorylase phosphatase in rat liver. Using substrates purified from liver, the apparent Km values of synthase phosphatase ([UDPglucose--glycogen glucosyltransferase-D]phosphohydrolase, EC 3.1.3.42) and phosphorylase phosphatase (phosphorylase a phosphohydrolase, EC 3.1.3.17) were found to be 0.7 and 60 units/ml respectively. The maximal velocity of phosphorylase phosphatase was more than a 100 times that of synthase phosphatase. In adrenalectomized, fasted animals there was a complete loss of synthase phosphatase but only a slight decrease in phosphorylase phosphatase when activity was measured using endogenous substrates in a concentrated liver extract. When assayed under optimal conditions with purified substrates, both activities were present but had decreased to very low levels. Mixing experiments indicated that synthase D present in the extract of adrenalectomized fasted animals was altered such that it was no longer a substrate for synthase phosphatase from normal rats. Phosphorylase a substrate on the other hand was unaltered and readily converted. When glucose was given in vivo, no change in percent of synthase in the I form was seen in adrenalectomized rats but the percent of phosphorylase in the a form was reduced. Precipitation of protein from an extract of normal fed rats with ethanol produced a large activation of phosphorylase phosphatase activity with no corresponding increase in synthase phosphatase activity. Despite the low phosphorylase phosphatase present in extracts of adrenalectomized fasted animals, ethanol precipitation increased activity to the same high level as obtained in the normal fed rats. Synthase phosphatase and phosphorylase phosphatase activities were also decreased in normal fasted, diabetic fed and fasted, and adrenalectomized fed rats. Both enzymes recovered in the same manner temporally after oral glucose administration to adrenalectomized, fasted rats. These results suggest an integrated regulatory mechanism for the two phosphatase."} {"id": "PMID:182272", "title": "Affinity chromatography of angiotensin I-converting enzyme from rabbit lung using hippurylhistidylleucyl-OH.", "content": "Approximately 50-fold purification of angiotensin I-converting enzyme (Peptidyldipeptide hydrolase, EC 3.4.15.1) from rabbit lung was achieved by affinity chromatography using the synthetic substrate Hippuryl-His-Leu-OH. The specific activity of the enzyme was increased from 0.044 units/mg protein to 1.911 units/mg protein for Hippuryl-His-Leu-OH and from 0.33 nmol/min per mg protein to 13.8 nmol/min per mg protein for angiotensin I.", "contents": "Affinity chromatography of angiotensin I-converting enzyme from rabbit lung using hippurylhistidylleucyl-OH. Approximately 50-fold purification of angiotensin I-converting enzyme (Peptidyldipeptide hydrolase, EC 3.4.15.1) from rabbit lung was achieved by affinity chromatography using the synthetic substrate Hippuryl-His-Leu-OH. The specific activity of the enzyme was increased from 0.044 units/mg protein to 1.911 units/mg protein for Hippuryl-His-Leu-OH and from 0.33 nmol/min per mg protein to 13.8 nmol/min per mg protein for angiotensin I."} {"id": "PMID:182273", "title": "Angiotensin I-converting enzyme from guinea pig lung and serum. A comparison of some kinetic and inhibition properties.", "content": "The angiotensin I-coverting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) was isolated from both guinea pig lung and serum; Km and V values were determined using both angiotensin I and hippurylhistidylleucine as substrates. Km values for the lung enzyme were 3.1 mM for hippurylhistidylleucine hippurylhistidylleucine and 0.076 mM for angiotensin I. Inhibition studies were performed and I50 values were obtained with the following inhibitors: angiotensin II (lung, 1.9 - 10(-5) M; serum, 1.7 - 10(-5) M), bradykinin (lung, 2.6 - 10(-6) M; serum, 2.1 - 10(-6) M), and pyrrolidone-Lys-Trp-Ala-Pro (lung, 7.9 - 10(-8) M; serum, 5.6 - 10(-8) M). Both enzymes were glycoproteins and were inhibited by concanavalin A. A maximum inhibition of 35% initial enzymatic activity was observed for both enzymes at a concanavalin A concentration of 4 - 10(-4) M suggesting that the sugar moieties of each enzyme are similar. Both enzymes required NaCl for activity and were inhibited by EDTA. A comparison of kinetic and inhibition properties indicates that both enzymes are quite similar.", "contents": "Angiotensin I-converting enzyme from guinea pig lung and serum. A comparison of some kinetic and inhibition properties. The angiotensin I-coverting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) was isolated from both guinea pig lung and serum; Km and V values were determined using both angiotensin I and hippurylhistidylleucine as substrates. Km values for the lung enzyme were 3.1 mM for hippurylhistidylleucine hippurylhistidylleucine and 0.076 mM for angiotensin I. Inhibition studies were performed and I50 values were obtained with the following inhibitors: angiotensin II (lung, 1.9 - 10(-5) M; serum, 1.7 - 10(-5) M), bradykinin (lung, 2.6 - 10(-6) M; serum, 2.1 - 10(-6) M), and pyrrolidone-Lys-Trp-Ala-Pro (lung, 7.9 - 10(-8) M; serum, 5.6 - 10(-8) M). Both enzymes were glycoproteins and were inhibited by concanavalin A. A maximum inhibition of 35% initial enzymatic activity was observed for both enzymes at a concanavalin A concentration of 4 - 10(-4) M suggesting that the sugar moieties of each enzyme are similar. Both enzymes required NaCl for activity and were inhibited by EDTA. A comparison of kinetic and inhibition properties indicates that both enzymes are quite similar."} {"id": "PMID:182274", "title": "Extraction of collagenase from the involuting rat uterus.", "content": "Collagenase (EC 3.4.24.3) activity can be measured directly in homogenates of the involuting rat uterus. Latent forms of collagenase are activated by a brief exposure to trypsin; trypsin activity is then blocked with soybean trypsin inhibitor. Homogenizing conditions have been developed that permit 90-95% recovery of the total active and latent collagenase activity in a 6000 X g pellet, where it is presumably bound to its collagen substrate. This insoluble activity can then be extracted by heating to 60 degrees C for 4 min in 0.04 M Tris - HCl buffer, pH 7.5, containing 0.1 M CaCl2. Methods are presented for the estimation of the recovery of collagenase in the extracts; this approximates 65-70% of the total. Small amounts of activity can also be extracted from rat liver and kidney. This extraction procedure should be of use in purifying collagenase without culturing the enzyme-producing tissue and in the direct assay of tissue collagenase activity. The activity extracted from rat uterus has been proven to be collagenase by its characteristic pattern of collagen breakdown products on disc electrophoresis and by the split of tropocollagen at interband 41 as shown by electron microscopy of reconstituted fragments. The activity is inhibited by EDTA, and this inhibition is not reversed by calcium or zinc ions.", "contents": "Extraction of collagenase from the involuting rat uterus. Collagenase (EC 3.4.24.3) activity can be measured directly in homogenates of the involuting rat uterus. Latent forms of collagenase are activated by a brief exposure to trypsin; trypsin activity is then blocked with soybean trypsin inhibitor. Homogenizing conditions have been developed that permit 90-95% recovery of the total active and latent collagenase activity in a 6000 X g pellet, where it is presumably bound to its collagen substrate. This insoluble activity can then be extracted by heating to 60 degrees C for 4 min in 0.04 M Tris - HCl buffer, pH 7.5, containing 0.1 M CaCl2. Methods are presented for the estimation of the recovery of collagenase in the extracts; this approximates 65-70% of the total. Small amounts of activity can also be extracted from rat liver and kidney. This extraction procedure should be of use in purifying collagenase without culturing the enzyme-producing tissue and in the direct assay of tissue collagenase activity. The activity extracted from rat uterus has been proven to be collagenase by its characteristic pattern of collagen breakdown products on disc electrophoresis and by the split of tropocollagen at interband 41 as shown by electron microscopy of reconstituted fragments. The activity is inhibited by EDTA, and this inhibition is not reversed by calcium or zinc ions."} {"id": "PMID:182275", "title": "Specific modification of the GTP binding sites of rat 5'-adenylic acid aminohydrolase by periodate-oxidized GTP.", "content": "1. Rat skeletal muscle AMP deaminase (AMP aminohydrolase, EC3.5.4.6) can be inactivated by incubation with the periodate-oxidized analogue of the enzyme inhibitor GTP. 2. Nucleoside triphosphates and KCl at high concentrations protect against inactivation, while ADP has no effect. 3. The inactivation can be reversed by the addition of GTP and amino acids and made irreversible by reduction with NaBH4. This indicates that, in the binding of the oxidized GTP to the enzyme, a Schiff base is formed between the aldehyde groups of the inhibitor and amino groups of the enzyme. 4. The kinetic properties of the reduced (oxidized GTP)-AMP deaminase derivative indicate that the loss of activity results from an increase in Km while no appreciable change in V is observed; consequently, the enzyme shows positive homotropic cooperativity even in the presence of optimal KCl concentration. 5. Since the treated enzyme shows kinetic properties similar to those of the native enzyme in the presence of GTP, and since the loss of sensitivity to GTP is directly proportional to the degree of inactivation, it is concluded that the oxidized GTP specifically modifies the binding sites for GTP. 6. Binding of the radioactive oxidized GTP shows that two binding sites for this reagent exist in the AMP deaminase molecule.", "contents": "Specific modification of the GTP binding sites of rat 5'-adenylic acid aminohydrolase by periodate-oxidized GTP. 1. Rat skeletal muscle AMP deaminase (AMP aminohydrolase, EC3.5.4.6) can be inactivated by incubation with the periodate-oxidized analogue of the enzyme inhibitor GTP. 2. Nucleoside triphosphates and KCl at high concentrations protect against inactivation, while ADP has no effect. 3. The inactivation can be reversed by the addition of GTP and amino acids and made irreversible by reduction with NaBH4. This indicates that, in the binding of the oxidized GTP to the enzyme, a Schiff base is formed between the aldehyde groups of the inhibitor and amino groups of the enzyme. 4. The kinetic properties of the reduced (oxidized GTP)-AMP deaminase derivative indicate that the loss of activity results from an increase in Km while no appreciable change in V is observed; consequently, the enzyme shows positive homotropic cooperativity even in the presence of optimal KCl concentration. 5. Since the treated enzyme shows kinetic properties similar to those of the native enzyme in the presence of GTP, and since the loss of sensitivity to GTP is directly proportional to the degree of inactivation, it is concluded that the oxidized GTP specifically modifies the binding sites for GTP. 6. Binding of the radioactive oxidized GTP shows that two binding sites for this reagent exist in the AMP deaminase molecule."} {"id": "PMID:182276", "title": "A study of phosphoglycerate kinase in human erythrocytes. I. Enzyme isolation, purification and assay.", "content": "The enzyme ATP-3-phospho-D-glycerate-1-phosphotransferase (EC 2.7.2.3) (phosphoglycerate kinase) has been isolated from human red cells in crystalline form by a modification of the method of Yoshida and Watanabe (1972) J. Biol. Chem. 247, 440-445). The crystalline enzyme was further purified by electrofocusing using carrier ampholytes (pH 7-9). The isoelectric point of phosphoglycerate kinase was estimated to be 8.75. The specific activity of purified phosphoglycerate kinase from electrofocusing was 2200 units per mg of protein at pH 8.3 (37 degrees C). Enzyme activity was assayed in the forward direction leading from 1,3-diphosphoglycerate to a 3-phosphoglycerate using a fluorimetric procedure for NAD-coupled enzymes for the measurement of the reaction rate at very low substrate concentrations. The auxiliary indicator enzymes were added in excess to yield true initial velocity kinetics, i.e. with no time lag upon addition of substrate (1,3-diphosphoglycerate). This was established theoretically using a mathematical model and confirmed experimentally. Further phosphoglycerate kinase was shown to be the rate-limiting step when the assay conditions were varied.", "contents": "A study of phosphoglycerate kinase in human erythrocytes. I. Enzyme isolation, purification and assay. The enzyme ATP-3-phospho-D-glycerate-1-phosphotransferase (EC 2.7.2.3) (phosphoglycerate kinase) has been isolated from human red cells in crystalline form by a modification of the method of Yoshida and Watanabe (1972) J. Biol. Chem. 247, 440-445). The crystalline enzyme was further purified by electrofocusing using carrier ampholytes (pH 7-9). The isoelectric point of phosphoglycerate kinase was estimated to be 8.75. The specific activity of purified phosphoglycerate kinase from electrofocusing was 2200 units per mg of protein at pH 8.3 (37 degrees C). Enzyme activity was assayed in the forward direction leading from 1,3-diphosphoglycerate to a 3-phosphoglycerate using a fluorimetric procedure for NAD-coupled enzymes for the measurement of the reaction rate at very low substrate concentrations. The auxiliary indicator enzymes were added in excess to yield true initial velocity kinetics, i.e. with no time lag upon addition of substrate (1,3-diphosphoglycerate). This was established theoretically using a mathematical model and confirmed experimentally. Further phosphoglycerate kinase was shown to be the rate-limiting step when the assay conditions were varied."} {"id": "PMID:182277", "title": "The refolding of lactate dehydrogenase subunits and their assembly to the functional tetramer.", "content": "The renaturation process of different lactate dehydrogenase isozymes (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from their unfolded subunits was investigated using a number of techniques. (a) kinetics of activity regain, (b) the kinetics of fluorescence change of fluoresecence change of the protein tryptophans, (c) kinetics of regain of the fluorescence properties of a covalently attached fluorescence probe (fluorescein) and (d) the kinetics of assembly, by following the intermediate oligomeric species appearing in the assembly pathway from monomers to tetramers. The results indicate that the unfolded polypeptide is converted to the active oligomeric species by the following scheme: Denatured subunit I leads to partially refolded subunit II leads to folded subunit III leads to dimer IV leads to tetramer. Step I and step II are first-order where step II is rate limiting. The ligands NAD+ and NADH accelerate step II, thus converting step I to the rate-limiting process. The fact that partially folded lactate dehydrogenase subunits are capable of co-enzyme binding may indicate the possible role of these ligands in the assembly of lactate dehydrogenase in vivo. Steps III and IV were found to be fast. The intermediate formation of an enzyme dimer which then dimerizes to the tetrameric species is found to be the major assembly pathway. Only a small portion of the lactate dehydrogenase tetramer is formed through the intermediate formation of a trimer intermediate.", "contents": "The refolding of lactate dehydrogenase subunits and their assembly to the functional tetramer. The renaturation process of different lactate dehydrogenase isozymes (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from their unfolded subunits was investigated using a number of techniques. (a) kinetics of activity regain, (b) the kinetics of fluorescence change of fluoresecence change of the protein tryptophans, (c) kinetics of regain of the fluorescence properties of a covalently attached fluorescence probe (fluorescein) and (d) the kinetics of assembly, by following the intermediate oligomeric species appearing in the assembly pathway from monomers to tetramers. The results indicate that the unfolded polypeptide is converted to the active oligomeric species by the following scheme: Denatured subunit I leads to partially refolded subunit II leads to folded subunit III leads to dimer IV leads to tetramer. Step I and step II are first-order where step II is rate limiting. The ligands NAD+ and NADH accelerate step II, thus converting step I to the rate-limiting process. The fact that partially folded lactate dehydrogenase subunits are capable of co-enzyme binding may indicate the possible role of these ligands in the assembly of lactate dehydrogenase in vivo. Steps III and IV were found to be fast. The intermediate formation of an enzyme dimer which then dimerizes to the tetrameric species is found to be the major assembly pathway. Only a small portion of the lactate dehydrogenase tetramer is formed through the intermediate formation of a trimer intermediate."} {"id": "PMID:182278", "title": "Effect of periodate oxidation on the structure and properties of glucose oxidase.", "content": "In order to elucidate the molecular structure of glucose oxidase (beta-D-glucose: oxygen 1-oxidoreductase, EC 1.1.3.4) and the roles of its carbohydrate moiety, chemical, physiochemical and immunological experiments were performed with enzyme samples before and after periodate oxidation. Hydrodynamic parameters indicated that the native enzyme was a globular protein with values of 1.21 for the frictional ratio and 43 A for the Stokes radius. The enzyme contained about 12% carbohydrate by weight, of which the main component was mannose. The periodate treatment decreased the carbohydrate content to about 40% of its original value. Slight modifications were detected in the absorbance spectrum and the content of arginyl residue. However, no significant alteration was brought about by this treatment in the catalytic parameters, immunological reactivities of the gross structure, not in the secondary and quaternary structures of the protein moity. Thermal denaturation temperature (about 72.5 degrees C) and the enthalpy of denaturation (about 450 kcal/mol) were common to the native and the periodate-oxodozed enzymes. The native was found to be quite resistant to sodium dodecyl sulfate and fairly stable to urea and heating. The periodate-oxidized enzyme was also stable to heat treatment, but it showed a diminished stability when denaturing agents were present. Kinetic analyses of the thermal inactivation processes showed that the entropy of activation was greatly decreased by the denaturing agents, especially in the case of the periodate-oxidized enzyme. It is concluded that the carbohydrate moiety of the enzyme plays a role in increasing the stability of the protein moiety, but does not directly participate in the catalytic activity, the immunological reactivity, or in maintaining the conformation of the enzyme protein.", "contents": "Effect of periodate oxidation on the structure and properties of glucose oxidase. In order to elucidate the molecular structure of glucose oxidase (beta-D-glucose: oxygen 1-oxidoreductase, EC 1.1.3.4) and the roles of its carbohydrate moiety, chemical, physiochemical and immunological experiments were performed with enzyme samples before and after periodate oxidation. Hydrodynamic parameters indicated that the native enzyme was a globular protein with values of 1.21 for the frictional ratio and 43 A for the Stokes radius. The enzyme contained about 12% carbohydrate by weight, of which the main component was mannose. The periodate treatment decreased the carbohydrate content to about 40% of its original value. Slight modifications were detected in the absorbance spectrum and the content of arginyl residue. However, no significant alteration was brought about by this treatment in the catalytic parameters, immunological reactivities of the gross structure, not in the secondary and quaternary structures of the protein moity. Thermal denaturation temperature (about 72.5 degrees C) and the enthalpy of denaturation (about 450 kcal/mol) were common to the native and the periodate-oxodozed enzymes. The native was found to be quite resistant to sodium dodecyl sulfate and fairly stable to urea and heating. The periodate-oxidized enzyme was also stable to heat treatment, but it showed a diminished stability when denaturing agents were present. Kinetic analyses of the thermal inactivation processes showed that the entropy of activation was greatly decreased by the denaturing agents, especially in the case of the periodate-oxidized enzyme. It is concluded that the carbohydrate moiety of the enzyme plays a role in increasing the stability of the protein moiety, but does not directly participate in the catalytic activity, the immunological reactivity, or in maintaining the conformation of the enzyme protein."} {"id": "PMID:182279", "title": "Lysine- and lysine-plus-threonine-inhibitable aspartokinases in Bacillus brevis.", "content": "Two aspartokinase (ATP:L-aspartate 4-phosphotrasferase, EC 2.7.2.4) enzyme activities have been identified and partially purified from Bacillus brevis. Aspartokinase I is subject to both inhibition and repression by lysine, and has a molecular weight in the region of 110 000. Aspartokinase II is a lysine-stabilised enzyme, inhibited multivalently by lysine plus theonine and has a molecular weight in the region of 95 000. This attern of aspartokinase activity has not been described previously and is unusual in that one end product (lysine) regulates two isoenzymes catalysing the first reaction of a branced biosynthetic pathway. In the absence of lysine, aspartokinase II changes to a more unstable non-inhibitable enzyme. Both enzymes are stabilised by sulphydryl reducing agents and have similar affinities for ATP, aspartate and lysine. However, there is no evidence for a view that they are products of a common gene. Problem concerned with the regulation of aspartokinase activities in Bacillus species are discussed.", "contents": "Lysine- and lysine-plus-threonine-inhibitable aspartokinases in Bacillus brevis. Two aspartokinase (ATP:L-aspartate 4-phosphotrasferase, EC 2.7.2.4) enzyme activities have been identified and partially purified from Bacillus brevis. Aspartokinase I is subject to both inhibition and repression by lysine, and has a molecular weight in the region of 110 000. Aspartokinase II is a lysine-stabilised enzyme, inhibited multivalently by lysine plus theonine and has a molecular weight in the region of 95 000. This attern of aspartokinase activity has not been described previously and is unusual in that one end product (lysine) regulates two isoenzymes catalysing the first reaction of a branced biosynthetic pathway. In the absence of lysine, aspartokinase II changes to a more unstable non-inhibitable enzyme. Both enzymes are stabilised by sulphydryl reducing agents and have similar affinities for ATP, aspartate and lysine. However, there is no evidence for a view that they are products of a common gene. Problem concerned with the regulation of aspartokinase activities in Bacillus species are discussed."} {"id": "PMID:182280", "title": "Substrate specificity of vetebrate collagenase.", "content": "Substrate specificity of purified tadpole collagenase (EC 3.4.24.3) has been studied using eleven synthetic peptides. A pentapeptide, t-butyloxycarbonylprolylalanylglycylisoleucylalanine amide, was susceptible to the action of the enzyme and an octapeptide, acetylprolylglutaminylglycylisoleucylalanylglycylglutaminylarginine ethyl ester, was proposed to be the best substrate for vertebrate collagenase among the peptides tested.", "contents": "Substrate specificity of vetebrate collagenase. Substrate specificity of purified tadpole collagenase (EC 3.4.24.3) has been studied using eleven synthetic peptides. A pentapeptide, t-butyloxycarbonylprolylalanylglycylisoleucylalanine amide, was susceptible to the action of the enzyme and an octapeptide, acetylprolylglutaminylglycylisoleucylalanylglycylglutaminylarginine ethyl ester, was proposed to be the best substrate for vertebrate collagenase among the peptides tested."} {"id": "PMID:182282", "title": "Evidence for the selective release of lysosomal proteinases in fasted rabbits.", "content": "The enzyme responsible for the conversion of \"neutral\" to \"alkaline\" fructose 1,6-bisphosphatase (EC 3.1.3.11) by removal of a 7000 dalton peptide (converting enzyme, Proteinase I) has been shown to be localized in rat liverlysosomes. Lysosomes also contain a specific proteinase (Proteinase II) that catalyzes the release of a small peptide from the NH2-terminus of the native subunits. In fasted rabbits Proteinase II is released into the cytoplasm, together with Cathepsin A, but Proteinase I remains associated with the lysosomal fraction. Increased osmotic fragility of liver lysosomes in fasted rabbits has also been observed, but this increased fragility does not result in the release of Proteinase I. The appearance of Proteinase II in the cytoplasm may be due either to its selective release from the lysosomes, without release of Proteinase I, or its localization in a different lysosomal fraction. Changes in lysosomal structure induced by fasting may play a dual role in : 1) the mobilization of amino acids for gluconeogenesis and 2) the modulation of activity of gluconeogenic enzymes.", "contents": "Evidence for the selective release of lysosomal proteinases in fasted rabbits. The enzyme responsible for the conversion of \"neutral\" to \"alkaline\" fructose 1,6-bisphosphatase (EC 3.1.3.11) by removal of a 7000 dalton peptide (converting enzyme, Proteinase I) has been shown to be localized in rat liverlysosomes. Lysosomes also contain a specific proteinase (Proteinase II) that catalyzes the release of a small peptide from the NH2-terminus of the native subunits. In fasted rabbits Proteinase II is released into the cytoplasm, together with Cathepsin A, but Proteinase I remains associated with the lysosomal fraction. Increased osmotic fragility of liver lysosomes in fasted rabbits has also been observed, but this increased fragility does not result in the release of Proteinase I. The appearance of Proteinase II in the cytoplasm may be due either to its selective release from the lysosomes, without release of Proteinase I, or its localization in a different lysosomal fraction. Changes in lysosomal structure induced by fasting may play a dual role in : 1) the mobilization of amino acids for gluconeogenesis and 2) the modulation of activity of gluconeogenic enzymes."} {"id": "PMID:182283", "title": "[Network of interactions between unlinked genes: synergistic and antagonistic regulation of iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2 synthesis].", "content": "Five chromosomal genes, CYPI to CYP5 involved in the regulation of the synthesis of iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2 are described. The function of these genes was studied either by varying the proportion of the mutated and wild type alleles in the cell vy varing the growth conditions, or else by transforming the mutants into sigma-cytoplasmic petites. We have shown a network of genetic interactions which regulate the synthesis of three structurally different proteins : iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2, by two unlinked genes : CYC1 and CYP1, one of which (CYC1) is the structural gene by iso-1-cytochrome c. Within this network the interactions are proportional to the gene dosage and are either antagonistic or synergistic depending on the allele combination and the protein studied. The mutated alleles cyp1 stimulate the synthesis of iso-2-cytochrome c, inhibit the synthesis of iso-1-cytochrome c, while the cytochrome b2 synthesis is also inhibited but by a combination of cyp1 mutated alleles CYC1 wild type allele. Other loci, CYP2, CYP3, CYP4 and CYP5 were also studied in various allelic combinations. They show some interactions between them or with CYC1 locus but these interactions are different and less pronounced than those involving loci CYP1 and CYC1.", "contents": "[Network of interactions between unlinked genes: synergistic and antagonistic regulation of iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2 synthesis]. Five chromosomal genes, CYPI to CYP5 involved in the regulation of the synthesis of iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2 are described. The function of these genes was studied either by varying the proportion of the mutated and wild type alleles in the cell vy varing the growth conditions, or else by transforming the mutants into sigma-cytoplasmic petites. We have shown a network of genetic interactions which regulate the synthesis of three structurally different proteins : iso-1-cytochrome c, iso-2-cytochrome c and cytochrome b2, by two unlinked genes : CYC1 and CYP1, one of which (CYC1) is the structural gene by iso-1-cytochrome c. Within this network the interactions are proportional to the gene dosage and are either antagonistic or synergistic depending on the allele combination and the protein studied. The mutated alleles cyp1 stimulate the synthesis of iso-2-cytochrome c, inhibit the synthesis of iso-1-cytochrome c, while the cytochrome b2 synthesis is also inhibited but by a combination of cyp1 mutated alleles CYC1 wild type allele. Other loci, CYP2, CYP3, CYP4 and CYP5 were also studied in various allelic combinations. They show some interactions between them or with CYC1 locus but these interactions are different and less pronounced than those involving loci CYP1 and CYC1."} {"id": "PMID:182284", "title": "Studies of the regulation and reaction mechanism of the carbamyl phosphate synthetase and aspartate transcarbamylase of bakers' yeast.", "content": "Kinetic studies of the carbamyl phosphate synthetase activity (CPSase) of bakers' yeast revealed an absolute requirement for K+ ions ; KM values for two of the substrates, glutamine and bicarbonate, were found to be 5 X 10(-4) M and 3 X 10(-3) M respectively. CPSase activity of the purified enzyme aggregate (M.W. 800,000) was extremely sensitive to UTP with a Ki of 2.4 X 10(-4) M. The purine nucleotide intermediate, XMP, was a strong activator of CPSase, acting at a site different from the regulatory site at which UTP binds ; XMP activation diminished at high concentrations of the substrate Mg-ATP. Studies of the reaction mechanism of CPSase revealed that it involved the sequential addition of the substrates bicarbonate and Mg-ATP, liberation of ADP, addition of glutamine, binding of ATP and then release of ADP and the product carbamyl phosphate. Studies of the reaction mechanism of the aspartate transcarbamylase (ATCase) of the aggregate yielded data which were not compatible with any of the usual models ; whichever reaction mechanism is ultivately found to fit the data, it will probably prove applicable both to the ATCase of the aggregate and to the disaggregated ATCase subunit (MW 138,000).", "contents": "Studies of the regulation and reaction mechanism of the carbamyl phosphate synthetase and aspartate transcarbamylase of bakers' yeast. Kinetic studies of the carbamyl phosphate synthetase activity (CPSase) of bakers' yeast revealed an absolute requirement for K+ ions ; KM values for two of the substrates, glutamine and bicarbonate, were found to be 5 X 10(-4) M and 3 X 10(-3) M respectively. CPSase activity of the purified enzyme aggregate (M.W. 800,000) was extremely sensitive to UTP with a Ki of 2.4 X 10(-4) M. The purine nucleotide intermediate, XMP, was a strong activator of CPSase, acting at a site different from the regulatory site at which UTP binds ; XMP activation diminished at high concentrations of the substrate Mg-ATP. Studies of the reaction mechanism of CPSase revealed that it involved the sequential addition of the substrates bicarbonate and Mg-ATP, liberation of ADP, addition of glutamine, binding of ATP and then release of ADP and the product carbamyl phosphate. Studies of the reaction mechanism of the aspartate transcarbamylase (ATCase) of the aggregate yielded data which were not compatible with any of the usual models ; whichever reaction mechanism is ultivately found to fit the data, it will probably prove applicable both to the ATCase of the aggregate and to the disaggregated ATCase subunit (MW 138,000)."} {"id": "PMID:182285", "title": "Further characterization of yeast RNA polymerases. Effect of subunits removal.", "content": "Two forms of yeast RNA polymerase A are resolved by phosphocellulose chromatography. One of these, called RNA polymerase A, is lacking two polypeptide chains of 48,000 and 37,000 daltons. The properties of the two enzymes are compared in the present paper. RNA polymerase A transcribes d(A-T)n with a similar efficiency as the complete enzyme, but it is comparatively much less active with native DNA. The two enzymes can also be differentiated on the basis of their ionic strength and divalent cation requirements. RNA polymerase A has a particularly low activity at high salt and low Mg2+ concentrations. Thermal inactivation curves of the two enzymes are different when residual activity is assayed with native DNA. In contrast with d(A-T)n as template the apparent inactivation curves of the two enzymes are identical. The data suggest that the two dissociable polypeptide chains play an important role in transcription. The template specificity of yeast RNA polymerase B was further investigated using SV40 DNA-FI as template. RNA polymerase B is able to retain [3H]SV40 DNA-FI on nitrocellulose filters but the enzyme-DNA complex is very unstable. The observation that RNA polymerase B can transcribe to some extent a supercoiled DNA but not a linear double stranded template supports the hypothesis that the enzyme needs some unpaired DNA structure to initiate transcription.", "contents": "Further characterization of yeast RNA polymerases. Effect of subunits removal. Two forms of yeast RNA polymerase A are resolved by phosphocellulose chromatography. One of these, called RNA polymerase A, is lacking two polypeptide chains of 48,000 and 37,000 daltons. The properties of the two enzymes are compared in the present paper. RNA polymerase A transcribes d(A-T)n with a similar efficiency as the complete enzyme, but it is comparatively much less active with native DNA. The two enzymes can also be differentiated on the basis of their ionic strength and divalent cation requirements. RNA polymerase A has a particularly low activity at high salt and low Mg2+ concentrations. Thermal inactivation curves of the two enzymes are different when residual activity is assayed with native DNA. In contrast with d(A-T)n as template the apparent inactivation curves of the two enzymes are identical. The data suggest that the two dissociable polypeptide chains play an important role in transcription. The template specificity of yeast RNA polymerase B was further investigated using SV40 DNA-FI as template. RNA polymerase B is able to retain [3H]SV40 DNA-FI on nitrocellulose filters but the enzyme-DNA complex is very unstable. The observation that RNA polymerase B can transcribe to some extent a supercoiled DNA but not a linear double stranded template supports the hypothesis that the enzyme needs some unpaired DNA structure to initiate transcription."} {"id": "PMID:182286", "title": "[Purification and mechanism of action of a plant galactokinase].", "content": "The previously described galactokinase from Fenugreek seeds, has been purified by affinity chromatography on a column of galactosamine-CH Sepharose. This material ensures a more specific fixation than does ATP-Sepharose. A 400 fold purification was achieved in a single step, with a 80 per cent yield. Km's for galactose and for Mg/ATP2- complex were respectively 0.54 x 10-3 M and 5, 10-3 M. Galactose-1-phosphate is a competitive inhibitor of galactose while the inhibition for Mg-ATP2- is not a competitive one. The Mg-ADP complex is a non-competitive inhibitor of both galactose and Mg-ATP2-. Moreover, the Km of the enzyme for M-ATP2- complex is modified when 2-deoxy- and 6-deoxy-galactose are used instead of galactose. These results are consistent with an ordered sequential mechanism for this galactokinase: galactose binds to the enzyme before Mg-ATP2-, and galactose-1-phosphate is the last reaction product liberated. The affinity of the kinase for 6-deoxygalactose is lower than for 2-deoxygalactose. This observation reveals the importance of the hydroxyl in C6 position for the binding on the enzyme.", "contents": "[Purification and mechanism of action of a plant galactokinase]. The previously described galactokinase from Fenugreek seeds, has been purified by affinity chromatography on a column of galactosamine-CH Sepharose. This material ensures a more specific fixation than does ATP-Sepharose. A 400 fold purification was achieved in a single step, with a 80 per cent yield. Km's for galactose and for Mg/ATP2- complex were respectively 0.54 x 10-3 M and 5, 10-3 M. Galactose-1-phosphate is a competitive inhibitor of galactose while the inhibition for Mg-ATP2- is not a competitive one. The Mg-ADP complex is a non-competitive inhibitor of both galactose and Mg-ATP2-. Moreover, the Km of the enzyme for M-ATP2- complex is modified when 2-deoxy- and 6-deoxy-galactose are used instead of galactose. These results are consistent with an ordered sequential mechanism for this galactokinase: galactose binds to the enzyme before Mg-ATP2-, and galactose-1-phosphate is the last reaction product liberated. The affinity of the kinase for 6-deoxygalactose is lower than for 2-deoxygalactose. This observation reveals the importance of the hydroxyl in C6 position for the binding on the enzyme."} {"id": "PMID:182287", "title": "Isolation and properties of a cyclic guanosine-monophosphate sensitive intracellular ribonuclease from Bacillus subtilis.", "content": "A ribonuclease was isolated and completely purified from sporulating cells of Bacillus subtilis. This RNase has a M.W. of about 150,000 daltons. It hydrolyzes single stranded RNA and single stranded synthetic polynucleotides yielding nucleoside 5'-monophosphates. The enzyme is an exonuclease which degrades polynucleotides from the 3'-end in the direction of the 5'-terminal. The RNase activity is strikingly inhibited by cGMP and to a lesser extent by cAMP. This inhibition (Ki = 0.1 mM) is of a non competitive nature. It appeared that in addition to the inhibition site, the enzyme contains a high affinity binding site for the two cyclic mononucleotides (K (cAMP) = 8.3 x 10-8; K (cGMP) = 2.5 x 10-7). The RNase activity is also strongly inhibited by spermidine. This inhibition appeared to be due to the polyamine binding with the RNA, thus lowering the affinity of the substrate for the active site of the enzyme. This RNase may play a role in vivo in selective degradation of newly synthesized mRNA during sporulation.", "contents": "Isolation and properties of a cyclic guanosine-monophosphate sensitive intracellular ribonuclease from Bacillus subtilis. A ribonuclease was isolated and completely purified from sporulating cells of Bacillus subtilis. This RNase has a M.W. of about 150,000 daltons. It hydrolyzes single stranded RNA and single stranded synthetic polynucleotides yielding nucleoside 5'-monophosphates. The enzyme is an exonuclease which degrades polynucleotides from the 3'-end in the direction of the 5'-terminal. The RNase activity is strikingly inhibited by cGMP and to a lesser extent by cAMP. This inhibition (Ki = 0.1 mM) is of a non competitive nature. It appeared that in addition to the inhibition site, the enzyme contains a high affinity binding site for the two cyclic mononucleotides (K (cAMP) = 8.3 x 10-8; K (cGMP) = 2.5 x 10-7). The RNase activity is also strongly inhibited by spermidine. This inhibition appeared to be due to the polyamine binding with the RNA, thus lowering the affinity of the substrate for the active site of the enzyme. This RNase may play a role in vivo in selective degradation of newly synthesized mRNA during sporulation."} {"id": "PMID:182288", "title": "Alteration of poly (ADP-Rib) synthesis during progesterone- caused gene expression in oviducts of quails.", "content": "The biological model of the selective induction of RNA synthesis in oviducts of estrogen stimulated immature quails by progesterone has been used to clarify whether poly (AD-Rib) is involved in DNA transcription. The chromatin-bound as well as the soluble poly (ADP-Rib) polymerase has been isolated from oviducts and the optimal reaction conditions have been determined. The activities, as measured by the incorporation rates of NAD+ into poly (ADP-Rib), of both, chromatin-bound \"endogenous\" polymerase (in the absense of \"exogenous\" DNA and histones) and soluble enzyme (native DNA-lysine-rich histone ratio: 4.3) from progesterone treated quail oviducts, have been determined to be only 30 per cent and 46 per cent respectively, as compared with the activities of the enzymes from the controls. This decrease in incorporation rates is apparently not due to an increased poly (ADP-Rib) degrading enzyme activity. Poly (ADP-Rib) synthesis in vivo was determined by incorporation studies with the precursor (14C) ribose. 12 h after intraperitoneal administration, 0.014 per cent of the total radioactivity was recovered in the oviduct histone fraction, 0.011 per cent in the oviduct nonhistone fraction and 0.009 per cent in the oviduct \"HCIextract\" containing the histone subfractions f1, f2 and f3. Among these histone subfractions f1 is ADP-ribosylated to the largest extent. ADP-ribosylation of f1 is less extensive in progesterone-stimulated oviducts (65 per cent) than in the controls (100 per cent). The present results suggest that in course of the selective, progesterone-induced DNA transcription the poly (ADP-Rib synthesis might drop.", "contents": "Alteration of poly (ADP-Rib) synthesis during progesterone- caused gene expression in oviducts of quails. The biological model of the selective induction of RNA synthesis in oviducts of estrogen stimulated immature quails by progesterone has been used to clarify whether poly (AD-Rib) is involved in DNA transcription. The chromatin-bound as well as the soluble poly (ADP-Rib) polymerase has been isolated from oviducts and the optimal reaction conditions have been determined. The activities, as measured by the incorporation rates of NAD+ into poly (ADP-Rib), of both, chromatin-bound \"endogenous\" polymerase (in the absense of \"exogenous\" DNA and histones) and soluble enzyme (native DNA-lysine-rich histone ratio: 4.3) from progesterone treated quail oviducts, have been determined to be only 30 per cent and 46 per cent respectively, as compared with the activities of the enzymes from the controls. This decrease in incorporation rates is apparently not due to an increased poly (ADP-Rib) degrading enzyme activity. Poly (ADP-Rib) synthesis in vivo was determined by incorporation studies with the precursor (14C) ribose. 12 h after intraperitoneal administration, 0.014 per cent of the total radioactivity was recovered in the oviduct histone fraction, 0.011 per cent in the oviduct nonhistone fraction and 0.009 per cent in the oviduct \"HCIextract\" containing the histone subfractions f1, f2 and f3. Among these histone subfractions f1 is ADP-ribosylated to the largest extent. ADP-ribosylation of f1 is less extensive in progesterone-stimulated oviducts (65 per cent) than in the controls (100 per cent). The present results suggest that in course of the selective, progesterone-induced DNA transcription the poly (ADP-Rib synthesis might drop."} {"id": "PMID:182291", "title": "Antibodies to herpes simplex virus types 1 and 2: a comparative study using indirect haemagglutination in carcinoma of the cervix and in other malignant conditions.", "content": "The authors used a technique of indirect haemagglutination to compare levels of antibody to Herpesvirus simplex types 1 and 2 in groups of patients with carcinoma of the cervix, together with other malignant conditions and in comparison to controls. A significant difference in the mean titre of antibody to type 2 virus is revealed between the carcinoma group and the B controls. The significance of the antibody assays is assessed by a study of the specificity of the antibodies found and by an assay of antibody which cross reacts with Herpesvirus simplex type 1.", "contents": "Antibodies to herpes simplex virus types 1 and 2: a comparative study using indirect haemagglutination in carcinoma of the cervix and in other malignant conditions. The authors used a technique of indirect haemagglutination to compare levels of antibody to Herpesvirus simplex types 1 and 2 in groups of patients with carcinoma of the cervix, together with other malignant conditions and in comparison to controls. A significant difference in the mean titre of antibody to type 2 virus is revealed between the carcinoma group and the B controls. The significance of the antibody assays is assessed by a study of the specificity of the antibodies found and by an assay of antibody which cross reacts with Herpesvirus simplex type 1."} {"id": "PMID:182292", "title": "Cytopathogenic XC assay for bone marrow from mice infected with murine leukemia viruses.", "content": "Virus production \"in vitro\" by bone marrow cells of murine leukemia virus-infected BALB/c mice was determined with a modified reverse XC cell assay. Bone marrow of mice infected by either Rauscher leukemia virus or Soul\u00e9 myeloid leukemia virus was cocultivated with XC cells and quantification was done by counting syncytia. During the development of both erythroblastosis and myeloid leukemia, the number of syncytia induced by cocultivation increased. High numbers of syncytia were especially obtained with myeloid leukemia cells; the phenomenon was evident as early as one month following inoculation with virus and before the onset of conspicuous clinical signs of disease.", "contents": "Cytopathogenic XC assay for bone marrow from mice infected with murine leukemia viruses. Virus production \"in vitro\" by bone marrow cells of murine leukemia virus-infected BALB/c mice was determined with a modified reverse XC cell assay. Bone marrow of mice infected by either Rauscher leukemia virus or Soul\u00e9 myeloid leukemia virus was cocultivated with XC cells and quantification was done by counting syncytia. During the development of both erythroblastosis and myeloid leukemia, the number of syncytia induced by cocultivation increased. High numbers of syncytia were especially obtained with myeloid leukemia cells; the phenomenon was evident as early as one month following inoculation with virus and before the onset of conspicuous clinical signs of disease."} {"id": "PMID:182293", "title": "[Blood platelet cyclic AMP and prostaglandin E1 before and during post-operative venous thrombosis].", "content": "The intracellular level of cyclic AMP and PGE1 in platelets of 19 patients before and on the third day after surgery was measured. Among these 19 patients, 11 developed venous thrombosis in the legs early after surgery. We found no correlation between the occurrence of thrombosis and the initial level of cyclic AMP of PGE1. Nevertheless, after surgery the mean values of cyclic AMP or PGE1 in both the groups with or without thrombosis were significantly decreased. For PGE1 levels statistical analysis of variance showed a significant difference between the individual variations, pointing out an \"individual factor\".", "contents": "[Blood platelet cyclic AMP and prostaglandin E1 before and during post-operative venous thrombosis]. The intracellular level of cyclic AMP and PGE1 in platelets of 19 patients before and on the third day after surgery was measured. Among these 19 patients, 11 developed venous thrombosis in the legs early after surgery. We found no correlation between the occurrence of thrombosis and the initial level of cyclic AMP of PGE1. Nevertheless, after surgery the mean values of cyclic AMP or PGE1 in both the groups with or without thrombosis were significantly decreased. For PGE1 levels statistical analysis of variance showed a significant difference between the individual variations, pointing out an \"individual factor\"."} {"id": "PMID:182295", "title": "Interactions between diverse proteinoids and microspheres in simulation of primordial evolution.", "content": "Experiments demonstrating an incorporation of different enzymelike activities into a single preparation of proteinoid microspheres provide a conceptual basis for the primitive lengthening of protometabolic pathways. An enhancement of one enzymelike activity by another proteinoid in the same microsphere has been found. This effect, plus the pathway-lengthening propensity of combinations of microspheres, indicates selective advantages contributing to adaptive protoselection. Data reported in this paper also bring into purview the concept of internally controlled variation. Inferences are derived for the origin of protosexuality in protocells. When allowance is made for a closer relationship to the environment than that needed in contemporary selection, the fundamental mechanistic requirements of protoevolution are regarded as met by the proteinoid microsphere.", "contents": "Interactions between diverse proteinoids and microspheres in simulation of primordial evolution. Experiments demonstrating an incorporation of different enzymelike activities into a single preparation of proteinoid microspheres provide a conceptual basis for the primitive lengthening of protometabolic pathways. An enhancement of one enzymelike activity by another proteinoid in the same microsphere has been found. This effect, plus the pathway-lengthening propensity of combinations of microspheres, indicates selective advantages contributing to adaptive protoselection. Data reported in this paper also bring into purview the concept of internally controlled variation. Inferences are derived for the origin of protosexuality in protocells. When allowance is made for a closer relationship to the environment than that needed in contemporary selection, the fundamental mechanistic requirements of protoevolution are regarded as met by the proteinoid microsphere."} {"id": "PMID:182297", "title": "Phenotypic expression of galactokinase deficiency in heterozygous and homozygous subjects: in vivo and in vitro studies.", "content": "Cultured fibroblasts derived from a patient homozygous for galactokinase deficiency, his parents, and controls had similar rates of growth in culture media where the only hexose was glucose. However, in media where the only hexose was galactose there was almost no growth of homozygous mutant cells or of maternal heterozygous cells and slight growth of paternal heterozygous cells. Growth of control cells was initially slow, but after a lag period (which coincided with increasing galactokinase activity) growth reached approximately the same levels as in glucose medium. In all cell lines there was a direct relation between the degree of enhancement of galactokinase activity and the ability of cells to adapt to growth in media where the only hexose was galactose. Erythrocyte galactokinase activities in a series of 24 children children with congenital cataracts aged 2-16 years were similar to those in 26 controls. One child in each of the cataract and control groups had 40-50% of mean control activity and was considered to be a potential heterozygote. Galactokinase deficiency (homozygous and heterozygous) is considered to be an uncommon cause of childhood cataracts. Nevertheless, it is an important cause since early dietary treatment can prevent or reverse lens opacities. The heterozygous state may be expressed phenotypically in the patient by the appearance of cataracts and in cultured cells by their defective growth in media where galactose is the only hexose.", "contents": "Phenotypic expression of galactokinase deficiency in heterozygous and homozygous subjects: in vivo and in vitro studies. Cultured fibroblasts derived from a patient homozygous for galactokinase deficiency, his parents, and controls had similar rates of growth in culture media where the only hexose was glucose. However, in media where the only hexose was galactose there was almost no growth of homozygous mutant cells or of maternal heterozygous cells and slight growth of paternal heterozygous cells. Growth of control cells was initially slow, but after a lag period (which coincided with increasing galactokinase activity) growth reached approximately the same levels as in glucose medium. In all cell lines there was a direct relation between the degree of enhancement of galactokinase activity and the ability of cells to adapt to growth in media where the only hexose was galactose. Erythrocyte galactokinase activities in a series of 24 children children with congenital cataracts aged 2-16 years were similar to those in 26 controls. One child in each of the cataract and control groups had 40-50% of mean control activity and was considered to be a potential heterozygote. Galactokinase deficiency (homozygous and heterozygous) is considered to be an uncommon cause of childhood cataracts. Nevertheless, it is an important cause since early dietary treatment can prevent or reverse lens opacities. The heterozygous state may be expressed phenotypically in the patient by the appearance of cataracts and in cultured cells by their defective growth in media where galactose is the only hexose."} {"id": "PMID:182298", "title": "Immediate and long-range effects of maternal viral infection in pregnancy.", "content": "A brief description of the pathogenesis and immediate and long-range outcome following certain maternal viral infections in pregnancy has been presented. As evidence has accumulated from the follow-up of infants with specific congenital infections, it is clear that the consequences can be disastrous but not just for the obviously affected neonate - the normal-appearing infant at birth may have problems which appear much later. So-called \"silent\" congenital infections of the central nervous system may be a more frequent cause of mental retardation and specific learning disorders than we realize.", "contents": "Immediate and long-range effects of maternal viral infection in pregnancy. A brief description of the pathogenesis and immediate and long-range outcome following certain maternal viral infections in pregnancy has been presented. As evidence has accumulated from the follow-up of infants with specific congenital infections, it is clear that the consequences can be disastrous but not just for the obviously affected neonate - the normal-appearing infant at birth may have problems which appear much later. So-called \"silent\" congenital infections of the central nervous system may be a more frequent cause of mental retardation and specific learning disorders than we realize."} {"id": "PMID:182299", "title": "Hallux syndactyly--ulnar polydactyly--abnormal ear lobes: a new syndrome.", "content": "A new syndrome is described. Its distinguishing features are hallux syndactyly, ulnar polydactyly and abnormal earlobes with other roentgenographic abnormalities along the medial border of the foot. It is inherited as an autosomal dominant.", "contents": "Hallux syndactyly--ulnar polydactyly--abnormal ear lobes: a new syndrome. A new syndrome is described. Its distinguishing features are hallux syndactyly, ulnar polydactyly and abnormal earlobes with other roentgenographic abnormalities along the medial border of the foot. It is inherited as an autosomal dominant."} {"id": "PMID:182301", "title": "[Role of alimentary hyperglycemia in the pathogenesis of several disorders of lipid metabolism].", "content": "Alimentary hyperglycemia in rabbits was found to be accompanied by increase in cholesterol level, as well as in the amount of triglycerides in the blood sera. Progressive increase in the serum concentration of pre-beta lipoproteids (serving as endogenous tryglyceride carrier) has also been demonstrated. A short-term feeding with cholesterol against the background of hyperglycemia in rabbits appeared to result in early marked atherosclerotic changes, as compared to those in control group of normoglycemic animals.", "contents": "[Role of alimentary hyperglycemia in the pathogenesis of several disorders of lipid metabolism]. Alimentary hyperglycemia in rabbits was found to be accompanied by increase in cholesterol level, as well as in the amount of triglycerides in the blood sera. Progressive increase in the serum concentration of pre-beta lipoproteids (serving as endogenous tryglyceride carrier) has also been demonstrated. A short-term feeding with cholesterol against the background of hyperglycemia in rabbits appeared to result in early marked atherosclerotic changes, as compared to those in control group of normoglycemic animals."} {"id": "PMID:182302", "title": "[Elaboration of chloramphenicol acetyltransferase by cells of E. coli K-12 under conditions altering the intracellular concentration of cyclic adenosine-3',5'-monophosphate].", "content": "The influence of cAMP, ACTH and glucose on the stimulation of chloramphenicol acetyl transferase synthesis in the cells of E. coli CSH-2/R222 and E. coli WZ-78/R222. (cya855) was examined. Glucose proved to decrease the enzyme synthesis in E. coli CSH-2/R222, causing catabolite repression; 5 mM of cAMP and 1000 mug/ml ACTH overcame the latter. The enzyme synthesis in E. coli WZ-78/R222 was insensitive to the catabolite repression; as to ACTH - it failed to cause stimulation ofchloramphenicol acetyl transferase synthesis in E. coli WZ-78/R222.", "contents": "[Elaboration of chloramphenicol acetyltransferase by cells of E. coli K-12 under conditions altering the intracellular concentration of cyclic adenosine-3',5'-monophosphate]. The influence of cAMP, ACTH and glucose on the stimulation of chloramphenicol acetyl transferase synthesis in the cells of E. coli CSH-2/R222 and E. coli WZ-78/R222. (cya855) was examined. Glucose proved to decrease the enzyme synthesis in E. coli CSH-2/R222, causing catabolite repression; 5 mM of cAMP and 1000 mug/ml ACTH overcame the latter. The enzyme synthesis in E. coli WZ-78/R222 was insensitive to the catabolite repression; as to ACTH - it failed to cause stimulation ofchloramphenicol acetyl transferase synthesis in E. coli WZ-78/R222."} {"id": "PMID:182303", "title": "[Effect of cyclic adenosine-3', 5'-monophosphate on cells of experimental lympholeukemia L-5178].", "content": "A study was made of the effect of cyclic adenosine-3',5'-monophosphate (cAMP) dibutyril-cAMP and theophylline (phosphoesterase inhibitor - an enzyme transforming adenosine-3'-5'-monophosphate into adenosine-5'-monophosphate) on the intensity of proliferation (by the increase in the content of nucleic acids in the culture), DNA synthesis (by the H3-thymidine incorporation) and on the transplantation properties (the capacity to repopulation in the animal organism) of leukemic cells of the L-5178 strain. It was found that cAMP in a concentration of 0.8 mM considerably inhibited the H3-thymidine incorporation, retarded the proliferation and decreased the transplantation capacity of leukemic cells. Theophylline and dibutyril-cAMP had a comparatively low inhibitory capacity on the DNA synthesis, proliferative activity and the transplantation properties of the cells.", "contents": "[Effect of cyclic adenosine-3', 5'-monophosphate on cells of experimental lympholeukemia L-5178]. A study was made of the effect of cyclic adenosine-3',5'-monophosphate (cAMP) dibutyril-cAMP and theophylline (phosphoesterase inhibitor - an enzyme transforming adenosine-3'-5'-monophosphate into adenosine-5'-monophosphate) on the intensity of proliferation (by the increase in the content of nucleic acids in the culture), DNA synthesis (by the H3-thymidine incorporation) and on the transplantation properties (the capacity to repopulation in the animal organism) of leukemic cells of the L-5178 strain. It was found that cAMP in a concentration of 0.8 mM considerably inhibited the H3-thymidine incorporation, retarded the proliferation and decreased the transplantation capacity of leukemic cells. Theophylline and dibutyril-cAMP had a comparatively low inhibitory capacity on the DNA synthesis, proliferative activity and the transplantation properties of the cells."} {"id": "PMID:182304", "title": "[Detection and study of a protein factor mediating stimulation of disulfide reductase activity by cyclic 3', 5'-AMP and other effectors].", "content": "DSR stimulation in the supernatant fraction under the effect of 3', 5'-AMP 10(-7) M, ATP 5.10(-5) M, Mg2+5.10(-5) M, EDTA 5.10(-4) M and protamine 5 mg/ml was mediated through a factor which was readily sorbed by BaSO4, Al (OH)3 and activated carbon, and was easily eluated with a 10-fold increase of the buffer molarity. Barium eluates of the liver and of the brain restored the effect of 3', 5'-AMP eliminated by BaSO4, crosswise and equally. Apparently, the sorbed factor was a protein since it was not dialyzed, very thermolabile and readily inactivated by a low trypsin concentrations. The factor restored the DSR activation eliminated or decreased by the protein proteinkinase inhibitor (PPKI). A linear relationship between active quantities of the PPKI and the protein factor were in favour of the fact that the protein factor was affiliated or identical to proteinkinase. A possible biological significance of the DSR activation and the hypothesis on the existence of a special protamine-sensitive proteinkinase is discussed.", "contents": "[Detection and study of a protein factor mediating stimulation of disulfide reductase activity by cyclic 3', 5'-AMP and other effectors]. DSR stimulation in the supernatant fraction under the effect of 3', 5'-AMP 10(-7) M, ATP 5.10(-5) M, Mg2+5.10(-5) M, EDTA 5.10(-4) M and protamine 5 mg/ml was mediated through a factor which was readily sorbed by BaSO4, Al (OH)3 and activated carbon, and was easily eluated with a 10-fold increase of the buffer molarity. Barium eluates of the liver and of the brain restored the effect of 3', 5'-AMP eliminated by BaSO4, crosswise and equally. Apparently, the sorbed factor was a protein since it was not dialyzed, very thermolabile and readily inactivated by a low trypsin concentrations. The factor restored the DSR activation eliminated or decreased by the protein proteinkinase inhibitor (PPKI). A linear relationship between active quantities of the PPKI and the protein factor were in favour of the fact that the protein factor was affiliated or identical to proteinkinase. A possible biological significance of the DSR activation and the hypothesis on the existence of a special protamine-sensitive proteinkinase is discussed."} {"id": "PMID:182305", "title": "[Enzyme activity of the bile and liver after disruption of its innervation and bile loss].", "content": "Continuous loss of bile in rats with a bile reservoir applied to the common bile duct caused an increase in specific activity of malic dehydrogenase, lactic dehydrogenase, glutamic dehydrogenase, glucose-6-phosphoric dehydrogenase, alkaline and acid phosphatase, urokinase and histidinase in the liver homogenates by the 7th day; the specific activity decreased by the 10th day. Disruption of innervation of the liver caused a sharp decrease of the ATP content and the abovementioned specifc activity in this organ. In continuous loss of bile there were revealed oscillations in the activity of the above-mentioned enzymes and sorbitol dehydrogenase in bile from the 1st to the 10th day of the experiment. Marked changes in the oscillations in the dysinnervated liver were in favour of the fact that those oscillations coursed under the control of the nervous system.", "contents": "[Enzyme activity of the bile and liver after disruption of its innervation and bile loss]. Continuous loss of bile in rats with a bile reservoir applied to the common bile duct caused an increase in specific activity of malic dehydrogenase, lactic dehydrogenase, glutamic dehydrogenase, glucose-6-phosphoric dehydrogenase, alkaline and acid phosphatase, urokinase and histidinase in the liver homogenates by the 7th day; the specific activity decreased by the 10th day. Disruption of innervation of the liver caused a sharp decrease of the ATP content and the abovementioned specifc activity in this organ. In continuous loss of bile there were revealed oscillations in the activity of the above-mentioned enzymes and sorbitol dehydrogenase in bile from the 1st to the 10th day of the experiment. Marked changes in the oscillations in the dysinnervated liver were in favour of the fact that those oscillations coursed under the control of the nervous system."} {"id": "PMID:182306", "title": "[Effect of early thymectomy on the growth of transplanted mammary gland tumors developing in mouse line C3Hf].", "content": "Mammary tumours which developed in factorless C3Hf mice when transplanted to MTV-S+ and MTV-S- recipients were found to grow at the same rate' early thymectomy failed to influence their growth. The observed accelerated growth of mammary tumour transplants from C3H/He mice to MTV-S+ recipients, as compared to the MTV-S- ones, and inhibition of the tumour growth after early thymectomy seemed to be connected with the peculiarities of the immunological reaction to the virus-induced antigens.", "contents": "[Effect of early thymectomy on the growth of transplanted mammary gland tumors developing in mouse line C3Hf]. Mammary tumours which developed in factorless C3Hf mice when transplanted to MTV-S+ and MTV-S- recipients were found to grow at the same rate' early thymectomy failed to influence their growth. The observed accelerated growth of mammary tumour transplants from C3H/He mice to MTV-S+ recipients, as compared to the MTV-S- ones, and inhibition of the tumour growth after early thymectomy seemed to be connected with the peculiarities of the immunological reaction to the virus-induced antigens."} {"id": "PMID:182308", "title": "[Catecholamine concentration in the hypothalamus following alteration of pituitary adrenocorticotropic function].", "content": "Norepinephrine, epinephrine and serotonin levels were studied in male rabbit hypothalamus and midbrain under the influence of different factors potentiating the hypophysial adrenocorticotropic function. Intensification of this adrenohypophysial function was accompanied by a certain decrease in the hypothalamic and midbrain norepinephrine level and by the appearance of epinephrine normally absent here. The role of serotonin in the regulation of the investigated pituitary function was not revealed since potentiation of this function was observed both with the lowered and with the elevated concentrations of this monoamine in the hypothalamus.", "contents": "[Catecholamine concentration in the hypothalamus following alteration of pituitary adrenocorticotropic function]. Norepinephrine, epinephrine and serotonin levels were studied in male rabbit hypothalamus and midbrain under the influence of different factors potentiating the hypophysial adrenocorticotropic function. Intensification of this adrenohypophysial function was accompanied by a certain decrease in the hypothalamic and midbrain norepinephrine level and by the appearance of epinephrine normally absent here. The role of serotonin in the regulation of the investigated pituitary function was not revealed since potentiation of this function was observed both with the lowered and with the elevated concentrations of this monoamine in the hypothalamus."} {"id": "PMID:182309", "title": "[Changes in leukocyte enzyme activity during experimental amyloidogenesis and in patients with amyloidosis].", "content": "The activity of hydrolytic and redox myeloperoxidase enzymes was determined in the neutrophils and lymphocytes of the peripheral blood of patients with secondary amyloidosis and also of the animals with amyloidogenesis and amyloidosis (caseine model). During the amyloidogenesis the activity of hyocrolytic enzymes and of myeloperoxidase in the neutrophils was found to decrease; this was particularly marked at the stage of the initial amyloid deposition. Changes in the enzyme activity in the animals against the background of already developed amyloidosis coincided with such in the blood cells of patients with secondary amyloidosis. The results obtained are discussed from the aspects of resorption theory.", "contents": "[Changes in leukocyte enzyme activity during experimental amyloidogenesis and in patients with amyloidosis]. The activity of hydrolytic and redox myeloperoxidase enzymes was determined in the neutrophils and lymphocytes of the peripheral blood of patients with secondary amyloidosis and also of the animals with amyloidogenesis and amyloidosis (caseine model). During the amyloidogenesis the activity of hyocrolytic enzymes and of myeloperoxidase in the neutrophils was found to decrease; this was particularly marked at the stage of the initial amyloid deposition. Changes in the enzyme activity in the animals against the background of already developed amyloidosis coincided with such in the blood cells of patients with secondary amyloidosis. The results obtained are discussed from the aspects of resorption theory."} {"id": "PMID:182310", "title": "[Effect of microvessel injury on the frequency of tumor cells' lodging in them].", "content": "The action of local laser-induced microvascular injury on the frequency of tumour-cell lodgement and on the ability of these cells to migrate out of the microvessel lumen was studied. Intravital TV-microscope with a videotape recorder and an ultra-voilet laser was used. Ascites Saidel hepatoma cells were injected into the blood stream of rats. Lodgement of tumour cells in the mesenteric vessels was observed but rarely (11%). The lodged cells adhered to the microvascular wall and gradually migrated from the lumen. The injury of the wall with laser beam results in the formation of microthrombi and in increase in the frequency of lodgement of the tumour cells in these vessels: 82% against 11%, but migration of these cells decreased. The data obtained supported the significance of the microthrombus formation in the metastatic process. However, this role is not one-sided since on the background of increased frequency of adhesion of the tumour cells there was noted a decrease in their motility in the course of several hours after the lodgement in the microvessels.", "contents": "[Effect of microvessel injury on the frequency of tumor cells' lodging in them]. The action of local laser-induced microvascular injury on the frequency of tumour-cell lodgement and on the ability of these cells to migrate out of the microvessel lumen was studied. Intravital TV-microscope with a videotape recorder and an ultra-voilet laser was used. Ascites Saidel hepatoma cells were injected into the blood stream of rats. Lodgement of tumour cells in the mesenteric vessels was observed but rarely (11%). The lodged cells adhered to the microvascular wall and gradually migrated from the lumen. The injury of the wall with laser beam results in the formation of microthrombi and in increase in the frequency of lodgement of the tumour cells in these vessels: 82% against 11%, but migration of these cells decreased. The data obtained supported the significance of the microthrombus formation in the metastatic process. However, this role is not one-sided since on the background of increased frequency of adhesion of the tumour cells there was noted a decrease in their motility in the course of several hours after the lodgement in the microvessels."} {"id": "PMID:182313", "title": "Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198.", "content": "Eight patients with Nelson's syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.", "contents": "Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198. Eight patients with Nelson's syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another."} {"id": "PMID:182318", "title": "The uptake of L-glutamate by the retina.", "content": "The accumulation of L[14C]glutamate by the isolated rat retina has been studied. When retinae were incubated at 37 degrees C in a medium containing L-[14C]glutamate, tissue/medium ratios of about 40:1 were achieved after 60 min. The labelled L-glutamate was rapidly metabolised and after 10 min about 50% of the radioactivity in the tissue amino acids was present as glutamine, aspartate, and 4-aminobutyrate (GABA). The process responsible for L-glutamate uptake showed many of the properties of an active uptake system: it was temperature sensitive, sodium dependent, inhibited by metabolic inhibitors and showed saturation kinetics. The saturable uptake process could be resolved into two components; a 'high' affinity process (apparent Km = 21 muM, Vmax = 35 nmoles/min/g tissue) and a 'low' affinity process (Km = 630 muM, Vmax = 881 nmoles/min/g tissue). The 'high' affinity and 'low' affinity uptake processes for L-glutamate appeared to have identical properties in the retina. The uptake of L-glutamate was not specific and was inhibited by other acidic amino acids including D-glutamate but not by neutral or basic amino acids. The retinal uptake of L-glutamate is not likely to be due to a homoexchange phenomenon because the retina was capable of achieving a large net uptake of glutamate and the efflux of L-[14C]glutamate from the tissue was not increased by the addition of non-radioactive L-glutamate to the incubation medium. Autoradiographic studies indicated that the sites for glutamate uptake are largely in the neuroglial Muller cells.", "contents": "The uptake of L-glutamate by the retina. The accumulation of L[14C]glutamate by the isolated rat retina has been studied. When retinae were incubated at 37 degrees C in a medium containing L-[14C]glutamate, tissue/medium ratios of about 40:1 were achieved after 60 min. The labelled L-glutamate was rapidly metabolised and after 10 min about 50% of the radioactivity in the tissue amino acids was present as glutamine, aspartate, and 4-aminobutyrate (GABA). The process responsible for L-glutamate uptake showed many of the properties of an active uptake system: it was temperature sensitive, sodium dependent, inhibited by metabolic inhibitors and showed saturation kinetics. The saturable uptake process could be resolved into two components; a 'high' affinity process (apparent Km = 21 muM, Vmax = 35 nmoles/min/g tissue) and a 'low' affinity process (Km = 630 muM, Vmax = 881 nmoles/min/g tissue). The 'high' affinity and 'low' affinity uptake processes for L-glutamate appeared to have identical properties in the retina. The uptake of L-glutamate was not specific and was inhibited by other acidic amino acids including D-glutamate but not by neutral or basic amino acids. The retinal uptake of L-glutamate is not likely to be due to a homoexchange phenomenon because the retina was capable of achieving a large net uptake of glutamate and the efflux of L-[14C]glutamate from the tissue was not increased by the addition of non-radioactive L-glutamate to the incubation medium. Autoradiographic studies indicated that the sites for glutamate uptake are largely in the neuroglial Muller cells."} {"id": "PMID:182319", "title": "Cytochemical localization of glucose-6-phosphatase activity in the central nervous system of the rat.", "content": "The histochemical detection of glucose-6-phosphatase (G-6-Pase) in neurons of the CNS has been confirmed at the level of electron microscope. Both glucose-6-phosphate (G-6-P) and alpha-glycerophosphate (alpha-gP) can be used as substrates to localize the reaction product of this enzyme, which we have found in all cell types of the cerebral cortex, cerebellum and brain stem. The reaction was most prominent in large neurons, such as the Purkinje cells of the cerebellum and the pyramidal cells of the cerebral cortex. This is due to their extensive content of rough and smooth endoplasmic reticulum, the ultrastructural sites of G-6-Pase activity. It was possible to measure quantitatively the hydrolysis of G-6-P and alpha-gP in brain homogenates and also in microsomal fractions, the biochemical correlate of the cytochemically demonstrable activity. These results call for a reappraisal of the previous biochemical evidence, which negates the existence of brain G-6-Pase, and consequently a reassessment of current concepts pertaining to the metabolic regulation of brain glucose.", "contents": "Cytochemical localization of glucose-6-phosphatase activity in the central nervous system of the rat. The histochemical detection of glucose-6-phosphatase (G-6-Pase) in neurons of the CNS has been confirmed at the level of electron microscope. Both glucose-6-phosphate (G-6-P) and alpha-glycerophosphate (alpha-gP) can be used as substrates to localize the reaction product of this enzyme, which we have found in all cell types of the cerebral cortex, cerebellum and brain stem. The reaction was most prominent in large neurons, such as the Purkinje cells of the cerebellum and the pyramidal cells of the cerebral cortex. This is due to their extensive content of rough and smooth endoplasmic reticulum, the ultrastructural sites of G-6-Pase activity. It was possible to measure quantitatively the hydrolysis of G-6-P and alpha-gP in brain homogenates and also in microsomal fractions, the biochemical correlate of the cytochemically demonstrable activity. These results call for a reappraisal of the previous biochemical evidence, which negates the existence of brain G-6-Pase, and consequently a reassessment of current concepts pertaining to the metabolic regulation of brain glucose."} {"id": "PMID:182321", "title": "Effects of morphine upon the lamina V type cells activities in the dorsal horn of the decerebrate cat.", "content": "The effects of morphine (2 mg/kg i.v.) upon the transmission of nociceptive messages at the spinal level have investigated in decerebrate cats by studying its effects on the activities of lamina V dorsal horn interneurons. In contrast to previous results obtained on the spinal cat, morphine had little or no effects on lamina V type cells in the decerebrate preparation. The mean values for spontaneous activity and responses to natural noxious stimulation were practically identical before and after morphine administration. Moreover, no significant depressive effect was found on responses induced by supramaximal transcutaneous stimulation. However, for this type of activity a depressive effect was revealed, if only the late component of units which presented bimodal responses were considered. We were unable to demonstrate after morphine administration an increase of the descending inhibitory effects induced on lamina V cells by stimulation of the central inferior nucleus of the raphe. Additional experiments using reversible spinalization (by cooling the cord at the thoracic level) suggest that the lack of effect of morphine on decerebrate animals could be explained by the fact that in this preparation, descending inhibitory influences are strongly exacerbated and thus may mask the depressive effects of this drug. These results indicate that the direct electrophysiological evidence of an increase of the descending control systems after morphine administration must be performed in the intact preparation in order to avoid the effects ot their exacerbation in the decerebrate state.", "contents": "Effects of morphine upon the lamina V type cells activities in the dorsal horn of the decerebrate cat. The effects of morphine (2 mg/kg i.v.) upon the transmission of nociceptive messages at the spinal level have investigated in decerebrate cats by studying its effects on the activities of lamina V dorsal horn interneurons. In contrast to previous results obtained on the spinal cat, morphine had little or no effects on lamina V type cells in the decerebrate preparation. The mean values for spontaneous activity and responses to natural noxious stimulation were practically identical before and after morphine administration. Moreover, no significant depressive effect was found on responses induced by supramaximal transcutaneous stimulation. However, for this type of activity a depressive effect was revealed, if only the late component of units which presented bimodal responses were considered. We were unable to demonstrate after morphine administration an increase of the descending inhibitory effects induced on lamina V cells by stimulation of the central inferior nucleus of the raphe. Additional experiments using reversible spinalization (by cooling the cord at the thoracic level) suggest that the lack of effect of morphine on decerebrate animals could be explained by the fact that in this preparation, descending inhibitory influences are strongly exacerbated and thus may mask the depressive effects of this drug. These results indicate that the direct electrophysiological evidence of an increase of the descending control systems after morphine administration must be performed in the intact preparation in order to avoid the effects ot their exacerbation in the decerebrate state."} {"id": "PMID:182322", "title": "Brain energy metabolism of the conscious rat exposed to various physiological and pathological situations.", "content": "Using a time-sharing fluorometer-reflectometer, pyridine nucleotide (NADH) and flavoprotein (Fp) fluorescence, as well as reflected light at the excitation wavelength, were measured and correlated with the electrical activity of an awake cerebral cortex. Exposure of the rat to a nitrogen atmosphere (anoxia) led to an increase in signals representing the reduction of pyridine nucleotides and flavins, with very similar kinetics. Inducement of partial ischemia by bilateral carotid artery ligation led to an increase in NADH, accompanied by a very small effect on the electrical activity (ECoG). In most animals, 2-3h after ligation, the ECoG became flat or depressed. Exposure of this ischemic cerebral cortex to KC1 solution caused depression of the electrical activity without metabolic response probably due to the limitation of oxygen supply. The metabolic state of an awake cerebral cortex was identified by exposing the brain to various levels of oxygen, epileptoform activity, spreading depression, hyperbaric pressure of oxygen and an uncoupler. From our results we conclude that the awake cerebral cortex is close to the resting state, state 4, rather than to the active state, state 3.", "contents": "Brain energy metabolism of the conscious rat exposed to various physiological and pathological situations. Using a time-sharing fluorometer-reflectometer, pyridine nucleotide (NADH) and flavoprotein (Fp) fluorescence, as well as reflected light at the excitation wavelength, were measured and correlated with the electrical activity of an awake cerebral cortex. Exposure of the rat to a nitrogen atmosphere (anoxia) led to an increase in signals representing the reduction of pyridine nucleotides and flavins, with very similar kinetics. Inducement of partial ischemia by bilateral carotid artery ligation led to an increase in NADH, accompanied by a very small effect on the electrical activity (ECoG). In most animals, 2-3h after ligation, the ECoG became flat or depressed. Exposure of this ischemic cerebral cortex to KC1 solution caused depression of the electrical activity without metabolic response probably due to the limitation of oxygen supply. The metabolic state of an awake cerebral cortex was identified by exposing the brain to various levels of oxygen, epileptoform activity, spreading depression, hyperbaric pressure of oxygen and an uncoupler. From our results we conclude that the awake cerebral cortex is close to the resting state, state 4, rather than to the active state, state 3."} {"id": "PMID:182323", "title": "Regulation of rat adrenal dopamine beta-hydroxylase. II. Receptor interaction in the regulation of enzyme synthesis and degradation.", "content": "Rat adrenal gland dopamine beta-hydroxylase is under neuronal regulation from the splanchnic nerve and hormonal control via adrenal cortical glucocorticoids. The regulatory systems act in different ways; neuronal stimuli induce dopamine beta-hydroxylase synthesis while hormonal stimulation inhibits enzyme degradation. Despite these mechanistic differences, both systems require a normally innervated cholinergic receptor to exert their effect. The enzyme response to either neural stimulation or ACTH administration is blocked by splanchnic denervation. Glucocorticoid stimulation of dopamine beta-hydroxylase, however, can occur after adrenal denervation, suggesting that ACTH acts on a receptor which requires splanchnic innervation, but glucocorticoids act distal to the receptor. Similar results were obtained when the effect of these manipulations were studied on phenylethanolamine N-methyltransferase, another enzyme in the catecholamine biosynthetic pathway. A model attempting to unify these and earlier findings is presented, in which the splanchnic nerve is involved in regulating both adrenal cortical glucocorticoidogenesis (by allowing ACTH to act on glucocorticoid synthesis) and adrenal medullary catecholamine biosynthesis (by induction of enzyme synthesis.).", "contents": "Regulation of rat adrenal dopamine beta-hydroxylase. II. Receptor interaction in the regulation of enzyme synthesis and degradation. Rat adrenal gland dopamine beta-hydroxylase is under neuronal regulation from the splanchnic nerve and hormonal control via adrenal cortical glucocorticoids. The regulatory systems act in different ways; neuronal stimuli induce dopamine beta-hydroxylase synthesis while hormonal stimulation inhibits enzyme degradation. Despite these mechanistic differences, both systems require a normally innervated cholinergic receptor to exert their effect. The enzyme response to either neural stimulation or ACTH administration is blocked by splanchnic denervation. Glucocorticoid stimulation of dopamine beta-hydroxylase, however, can occur after adrenal denervation, suggesting that ACTH acts on a receptor which requires splanchnic innervation, but glucocorticoids act distal to the receptor. Similar results were obtained when the effect of these manipulations were studied on phenylethanolamine N-methyltransferase, another enzyme in the catecholamine biosynthetic pathway. A model attempting to unify these and earlier findings is presented, in which the splanchnic nerve is involved in regulating both adrenal cortical glucocorticoidogenesis (by allowing ACTH to act on glucocorticoid synthesis) and adrenal medullary catecholamine biosynthesis (by induction of enzyme synthesis.)."} {"id": "PMID:182325", "title": "CYCLIC AMP/*SECRETl cyclic AMP into push-pull perfusates in freely moving rats.", "content": "Cyclic AMP was found in perfusates of push-pull cannula's, chronically placed in the lateral ventricle of freely moving rats. After addition of norepinephrine, dopamine or adenosine to the perfusates the output of cyclic AMP was enhanced, whilst serotonin and histamine were found to be ineffective. The effects of noradrenaline and dopamine on cyclic AMP were found to be mediated by different receptors: haloperidol antagonized only the dopamine response. The effect of norepinephrine was mimicked by isoprenaline, a beta-adrenergic agonist, but was not blocked by propranolol. L-DOPA, given intraperitoneally, increased cyclic AMP levels in the perfusate. We conclude that the release of cyclic AMP into the extracellular medium is a normally occurring phenomenon in brain tissue.", "contents": "CYCLIC AMP/*SECRETl cyclic AMP into push-pull perfusates in freely moving rats. Cyclic AMP was found in perfusates of push-pull cannula's, chronically placed in the lateral ventricle of freely moving rats. After addition of norepinephrine, dopamine or adenosine to the perfusates the output of cyclic AMP was enhanced, whilst serotonin and histamine were found to be ineffective. The effects of noradrenaline and dopamine on cyclic AMP were found to be mediated by different receptors: haloperidol antagonized only the dopamine response. The effect of norepinephrine was mimicked by isoprenaline, a beta-adrenergic agonist, but was not blocked by propranolol. L-DOPA, given intraperitoneally, increased cyclic AMP levels in the perfusate. We conclude that the release of cyclic AMP into the extracellular medium is a normally occurring phenomenon in brain tissue."} {"id": "PMID:182328", "title": "Factors affecting uptake and retention of technetium-99m-diphosphonate and 99m-pertechnetate in osseous, connective and soft tissues.", "content": "The bone scanning complex, 99mTc-Sn-EHDP, consisting of the nuclide technetium-99m, stannous ion and ethane-1-hydroxy-1,1-diphosphonate, administered intravenously is retained in soft tissues in proportion to increasing calcium content of the tissues. Within bone tissue, the retention is proportional to vascularity and to surface area of calcium phosphate in bones and not necessarily to calcium and phosphate concentration. The nuclidic agent 99mTcO4-BUT NOT THE 99MTc-diphosphonate is selectively taken up by the thyroid and this uptake can be blocked by administering sodium perchlorate. Among the connective tissues studied, the tracheal cartilage seems to have the greatest potential to calcify with increasing age of the animal and man. Soft tissue does not retain the bone scanning complex 99mTc-Sn-EHDP but does retain 99mTcO4-.", "contents": "Factors affecting uptake and retention of technetium-99m-diphosphonate and 99m-pertechnetate in osseous, connective and soft tissues. The bone scanning complex, 99mTc-Sn-EHDP, consisting of the nuclide technetium-99m, stannous ion and ethane-1-hydroxy-1,1-diphosphonate, administered intravenously is retained in soft tissues in proportion to increasing calcium content of the tissues. Within bone tissue, the retention is proportional to vascularity and to surface area of calcium phosphate in bones and not necessarily to calcium and phosphate concentration. The nuclidic agent 99mTcO4-BUT NOT THE 99MTc-diphosphonate is selectively taken up by the thyroid and this uptake can be blocked by administering sodium perchlorate. Among the connective tissues studied, the tracheal cartilage seems to have the greatest potential to calcify with increasing age of the animal and man. Soft tissue does not retain the bone scanning complex 99mTc-Sn-EHDP but does retain 99mTcO4-."} {"id": "PMID:182329", "title": "Effect of estrogen on the collagenolytic activity of rat bone.", "content": "Rats were injected with 17 beta-estradiol benzoate intramuscularly and the collagenolytic activity of the rat bones was assayed by measuring the degradation of purified reconstituted 3H-proline- and 3H-hydroxyproline-labeled collagen. A diminution of the collagenolytic activity which could be recovered from the culture medium of estrogen-treated rat bone was observed. However, the addition of estrogen to the enzyme using the same assay revealed no diminution of collagenolytic activity. These results suggest that the diminution of collagenolytic activity in the culture medium of estrogen-treated rat bone is due to an alteration in the production or activation of collagenolytic activity.", "contents": "Effect of estrogen on the collagenolytic activity of rat bone. Rats were injected with 17 beta-estradiol benzoate intramuscularly and the collagenolytic activity of the rat bones was assayed by measuring the degradation of purified reconstituted 3H-proline- and 3H-hydroxyproline-labeled collagen. A diminution of the collagenolytic activity which could be recovered from the culture medium of estrogen-treated rat bone was observed. However, the addition of estrogen to the enzyme using the same assay revealed no diminution of collagenolytic activity. These results suggest that the diminution of collagenolytic activity in the culture medium of estrogen-treated rat bone is due to an alteration in the production or activation of collagenolytic activity."} {"id": "PMID:182340", "title": "Status of tRNA charging, trinucleotide acceptor sequence and tRNA nucleotidyltransferase activity in the human placenta.", "content": "Samples of tRNA isolated from the cell sap of full-term human placenta were found to have a low capacity for accepting amino acids in the presence of partially purified synthetase preparations made from placental or rat liver cell sap. Gel electrophoresis of placental tRNA showed that part of this could be accounted for by gross degradation. The proportion of chargeable tRNA carrying amino acids was estimated by periodate oxidation followed by stripping and then charging with labeled amino acids. Only 50% of chargeable placental tRNA was in the charged state when isolated, whereas 87% of freshly isolated rat liver tRNA was found to be charged with amino acids. A fraction from placental cell sap was shown to have tRNA nucleotidyltransferase activity. When placental tRNA was incubated with this fraction and [3H]ATP or [3H]CTP, ATP was incorporated into about 12% of the tRNA molecules and CTP into 5-7%. When rat liver tRNA was used in place of placental tRNA, [3H]ATP was incorporated into less than 5% of the tRNA molecules. By using snake-venom diesterase over short periods of incubation, it was confirmed that the ATP had been incorporated terminally as AMP into the placental tRNA. These observations show that, in contrast to rat liver tRNA, tRNA prepared from human placenta is poorly charged with amino acids, many of the molecules lack the acceptor trinucleotide and there is extensive degradation beyond this stage.", "contents": "Status of tRNA charging, trinucleotide acceptor sequence and tRNA nucleotidyltransferase activity in the human placenta. Samples of tRNA isolated from the cell sap of full-term human placenta were found to have a low capacity for accepting amino acids in the presence of partially purified synthetase preparations made from placental or rat liver cell sap. Gel electrophoresis of placental tRNA showed that part of this could be accounted for by gross degradation. The proportion of chargeable tRNA carrying amino acids was estimated by periodate oxidation followed by stripping and then charging with labeled amino acids. Only 50% of chargeable placental tRNA was in the charged state when isolated, whereas 87% of freshly isolated rat liver tRNA was found to be charged with amino acids. A fraction from placental cell sap was shown to have tRNA nucleotidyltransferase activity. When placental tRNA was incubated with this fraction and [3H]ATP or [3H]CTP, ATP was incorporated into about 12% of the tRNA molecules and CTP into 5-7%. When rat liver tRNA was used in place of placental tRNA, [3H]ATP was incorporated into less than 5% of the tRNA molecules. By using snake-venom diesterase over short periods of incubation, it was confirmed that the ATP had been incorporated terminally as AMP into the placental tRNA. These observations show that, in contrast to rat liver tRNA, tRNA prepared from human placenta is poorly charged with amino acids, many of the molecules lack the acceptor trinucleotide and there is extensive degradation beyond this stage."} {"id": "PMID:182341", "title": "The synthesis of apoproteins of very low density lipoproteins isolated from the Golgi apparatus of rat liver.", "content": "The incorporation of [3H]leucine in vivo into very low density lipoproteins (VLDL) from the rat hepatic Golgi apparatus and serum was studied. A Golgi-rich fraction isolated on a discontinuous sucrose gradient between 0.5 and 1.1 M was found to contain VLDL having common antigenic determinants with serum VLDL. The incorporation of the [3H]leucine into the Golgi VLDL and serum VLDL suggested a precursor-product relationship. Analysis of the apoproteins of the Golgi VLDL by polacrylamide gel electrophoresis revealed protein bands with similar mobility to those of serum VLDL, except that the former contained virtually no rapidly migrating peptides with the mobility of serum apo-C-II and apo-C-III. The pattern of incorporation of the [3H]leucine into the apoproteins was similar in VLDL from Golgi apparatus and serum, except for the absence of radioactivity in the area of the gel of Golgi apo-VLDL corresponding to apo-C-II and apo-C-III. The radioactive amino acid was incorporated predominantly into the Golgi apo-VLDL bands with similar mobility to apo-B and an apoprotein or group of apoproteins containing the arginine-rich peptide of serum VLDL. In vitro incubation of the Golgi VLDL with [3H]leucine-labeled HDL resulted in the acquisition of a number of proteins, including the rapidly migrating proteins. Administration of colchicine prior to the injection of [3H]leucine resulted in the appearance of gel bands and radioactivity in the apo-C-II and apo-C-III areas of Golgi apo-VLDL, suggesting that these can be acquired if secretion of VLDL is slowed or inhibited. The hepatic Golgi apparatus was then divided into fractions of predominantly forming face (GF3) or secretory granules (GF1). After polyacrylamide gel electrophoresis of the apo-VLDL from GF, no visible bands or incorporation of [3H]leucine was found in the region of apo-C-II or apo-C-III. However VLDL from GF1, showed visible and radioactive bands in the apo-C-II and apo-C-III area although they represented a much smaller proportion of the total apoprotein than was found in the corresponding serum apo-VLDL. In the isolated perfused liver the percentage incorporation of [3H]leucine into the rapidly migrating apoproteins of Golgi VLDL was considerably less than that found in the corresponding apoproteins of perfusate VLDL, where circulating C lipoproteins are virtually absent. The data indicate that nascent VLDL begins to acquire the C-II and C-III apoproteins during its passage through the Golgi apparatus but that the main acquisition occurs during or after secretion into the space of Disse.", "contents": "The synthesis of apoproteins of very low density lipoproteins isolated from the Golgi apparatus of rat liver. The incorporation of [3H]leucine in vivo into very low density lipoproteins (VLDL) from the rat hepatic Golgi apparatus and serum was studied. A Golgi-rich fraction isolated on a discontinuous sucrose gradient between 0.5 and 1.1 M was found to contain VLDL having common antigenic determinants with serum VLDL. The incorporation of the [3H]leucine into the Golgi VLDL and serum VLDL suggested a precursor-product relationship. Analysis of the apoproteins of the Golgi VLDL by polacrylamide gel electrophoresis revealed protein bands with similar mobility to those of serum VLDL, except that the former contained virtually no rapidly migrating peptides with the mobility of serum apo-C-II and apo-C-III. The pattern of incorporation of the [3H]leucine into the apoproteins was similar in VLDL from Golgi apparatus and serum, except for the absence of radioactivity in the area of the gel of Golgi apo-VLDL corresponding to apo-C-II and apo-C-III. The radioactive amino acid was incorporated predominantly into the Golgi apo-VLDL bands with similar mobility to apo-B and an apoprotein or group of apoproteins containing the arginine-rich peptide of serum VLDL. In vitro incubation of the Golgi VLDL with [3H]leucine-labeled HDL resulted in the acquisition of a number of proteins, including the rapidly migrating proteins. Administration of colchicine prior to the injection of [3H]leucine resulted in the appearance of gel bands and radioactivity in the apo-C-II and apo-C-III areas of Golgi apo-VLDL, suggesting that these can be acquired if secretion of VLDL is slowed or inhibited. The hepatic Golgi apparatus was then divided into fractions of predominantly forming face (GF3) or secretory granules (GF1). After polyacrylamide gel electrophoresis of the apo-VLDL from GF, no visible bands or incorporation of [3H]leucine was found in the region of apo-C-II or apo-C-III. However VLDL from GF1, showed visible and radioactive bands in the apo-C-II and apo-C-III area although they represented a much smaller proportion of the total apoprotein than was found in the corresponding serum apo-VLDL. In the isolated perfused liver the percentage incorporation of [3H]leucine into the rapidly migrating apoproteins of Golgi VLDL was considerably less than that found in the corresponding apoproteins of perfusate VLDL, where circulating C lipoproteins are virtually absent. The data indicate that nascent VLDL begins to acquire the C-II and C-III apoproteins during its passage through the Golgi apparatus but that the main acquisition occurs during or after secretion into the space of Disse."} {"id": "PMID:182342", "title": "The induced biosynthesis of 7-dehydrocholesterols in yeast: potential sources of new provitamin D3 analogs.", "content": "The effect of low concentrations of a specifically designed sterol-24-transmethylase inhibitor, 25-aza-24, 25-dihydrozymosterol (10) on sterol production in Saccharomyces cerevisiae was examined. The synthesis of cholesta-5,7,22,24-tetraen-3beta-ol (4), its 7,22,24 analog (15) and the 7,24 analog (5) coupled with the availability of zymosterol (6) and cholesta-5,7,24-3beta-ol (3) derivatives facilitated a search for these sterols in cultures treated with this inhibitor. When S. cerevisiae was grown in the presence of 1.3 and 5 muM 10, it produced no ergosterol but accumulated zymosterol (6), cholesta-5,7,22,24-tetraen-3beta-ol (4) and related C27 sterols (3 and 5). These results indicate blockage of the side chain methylation that normally occurs during the biosynthesis of ergosterol in yeast by compound 10 is efficient. The cholesta-5,7,22,24-tetraen-3beta-ol is a close structural analog of provitamin D3 (7-dehydrocholesterol). The inhibited yeast thus provides a source of a potentially new provitamin D3 substitute.", "contents": "The induced biosynthesis of 7-dehydrocholesterols in yeast: potential sources of new provitamin D3 analogs. The effect of low concentrations of a specifically designed sterol-24-transmethylase inhibitor, 25-aza-24, 25-dihydrozymosterol (10) on sterol production in Saccharomyces cerevisiae was examined. The synthesis of cholesta-5,7,22,24-tetraen-3beta-ol (4), its 7,22,24 analog (15) and the 7,24 analog (5) coupled with the availability of zymosterol (6) and cholesta-5,7,24-3beta-ol (3) derivatives facilitated a search for these sterols in cultures treated with this inhibitor. When S. cerevisiae was grown in the presence of 1.3 and 5 muM 10, it produced no ergosterol but accumulated zymosterol (6), cholesta-5,7,22,24-tetraen-3beta-ol (4) and related C27 sterols (3 and 5). These results indicate blockage of the side chain methylation that normally occurs during the biosynthesis of ergosterol in yeast by compound 10 is efficient. The cholesta-5,7,22,24-tetraen-3beta-ol is a close structural analog of provitamin D3 (7-dehydrocholesterol). The inhibited yeast thus provides a source of a potentially new provitamin D3 substitute."} {"id": "PMID:182343", "title": "Versatility of oxazolidine spin labels--a model study with acyl-alpha-chymotrypsin.", "content": "The p-nitrophenyl ester of N-oxyl-4',4'-dimethyl-3-oxazolidinebutyric acid was synthesized. The resonance spectrum of the acyl-alpha-chymotrypsin intermediate of this substrate was found to have more motional freedom at the enzyme active site as compared to the acyl-enzyme prepared from the p-nitrophenyl esters of 1-oxyl-2,2,5,5-tetramethyl-3-carboxypyrrolidine and 1-oxyl-2,2,6,6-tetramethyl-4-carboxy-1,2,5,6-tetrahydropyridine. The flexibility and the versatility of Keana's oxazolidine spin labels as covalent conformational probes is discussed.", "contents": "Versatility of oxazolidine spin labels--a model study with acyl-alpha-chymotrypsin. The p-nitrophenyl ester of N-oxyl-4',4'-dimethyl-3-oxazolidinebutyric acid was synthesized. The resonance spectrum of the acyl-alpha-chymotrypsin intermediate of this substrate was found to have more motional freedom at the enzyme active site as compared to the acyl-enzyme prepared from the p-nitrophenyl esters of 1-oxyl-2,2,5,5-tetramethyl-3-carboxypyrrolidine and 1-oxyl-2,2,6,6-tetramethyl-4-carboxy-1,2,5,6-tetrahydropyridine. The flexibility and the versatility of Keana's oxazolidine spin labels as covalent conformational probes is discussed."} {"id": "PMID:182344", "title": "Diphosphoinositide metabolism in bovine adrenal medulla.", "content": "(1) A phosphatidylinositol kinase (EC 2.7.1.67) of a chromaffin vesicle membrane preparation isolated from bovine adrenal medulla was characterized. Its activity towards endogenous and exogenous phosphatidylinositol was very similar to the kinase activity of the microsomal fraction prepared from the same tissue. (2) Phosphomonoesterase (EC 3.1.3.36) and diesterase activity hydrolysing membrane bound phosphatidylinositol 4-phosphate was located mainly in the microsomal fraction. No hydrolytic activity was present in the vesicle membrane. (3) Phosphorylation of chromaffin vesicle membrane phosphatidylinositol did not increase calcium-binding by the membranes.", "contents": "Diphosphoinositide metabolism in bovine adrenal medulla. (1) A phosphatidylinositol kinase (EC 2.7.1.67) of a chromaffin vesicle membrane preparation isolated from bovine adrenal medulla was characterized. Its activity towards endogenous and exogenous phosphatidylinositol was very similar to the kinase activity of the microsomal fraction prepared from the same tissue. (2) Phosphomonoesterase (EC 3.1.3.36) and diesterase activity hydrolysing membrane bound phosphatidylinositol 4-phosphate was located mainly in the microsomal fraction. No hydrolytic activity was present in the vesicle membrane. (3) Phosphorylation of chromaffin vesicle membrane phosphatidylinositol did not increase calcium-binding by the membranes."} {"id": "PMID:182345", "title": "Cyclic nucleotides in spinal cells.", "content": "The most striking effects of intracellular injections of adenosine 3'5'-cyclic monophosphate (cAMP) into spinal mononeurons in cats are a speeding-up of the action potential, both its rising and falling phase, and a potentiation of the after-hyperpolarization; the latter porbably indicates a marked enhancement of Ca2+ influx. In this respect, cAMP and guanosine 3'5'-cyclic monophosphate (cGMP) have similar actions, though cAMP appears to be more potent. It is suggested that through this mechanism, cyclic nucleotides may play an important role in synaptic facilitation. Changes in resting membrane potential and resistance are less conspicuous or predictable. By contrast, both agents, when injected into unresponsive cells, presumed to be neuroglia, regularly cause a drop in membrane resistance; this is associated with hyperpolarization and therefore likely to reflect an increase in membrane K+ conductance.", "contents": "Cyclic nucleotides in spinal cells. The most striking effects of intracellular injections of adenosine 3'5'-cyclic monophosphate (cAMP) into spinal mononeurons in cats are a speeding-up of the action potential, both its rising and falling phase, and a potentiation of the after-hyperpolarization; the latter porbably indicates a marked enhancement of Ca2+ influx. In this respect, cAMP and guanosine 3'5'-cyclic monophosphate (cGMP) have similar actions, though cAMP appears to be more potent. It is suggested that through this mechanism, cyclic nucleotides may play an important role in synaptic facilitation. Changes in resting membrane potential and resistance are less conspicuous or predictable. By contrast, both agents, when injected into unresponsive cells, presumed to be neuroglia, regularly cause a drop in membrane resistance; this is associated with hyperpolarization and therefore likely to reflect an increase in membrane K+ conductance."} {"id": "PMID:182347", "title": "Response of serum cholesterol and triglycerides to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer.", "content": "Cholesterol and triglycerides were measured in plasma samples from patient with cancer of the prostate before and after 3 months treatment with either Premarin, Provera, Provera and diethylstilbestrol, or diethylstilbestrol alone. Cholesterol was also measured before and after one of three doses of diethylstilbestrol or placebo. Pretreatment cholesterol levels at 196 +/- 1.3 mg per 100 ml (X +/- SE, N = 1093) were significantly lower than these reported for similar age group noncancer controls. Significant increases occurred with some of the estrogen treatments. Pretreatment cholesterol levels showed a significant negative correlation with age in Stage III and IV patients of both studies and a positive correlation with hemoglobin in Stage III patients of both studies. Pretreatment triglyceride levels at 120 +/- 1.9 mg per 100 ml (X +/- SE, N = 1089) were similar to levels reported for noncancer controls of similar age. Estrogen treatment produced a significant increase in triglyceride levels. Serum triglycerides were significantly correlated with hemoglobin, weight, and cholesterol and negatively correlated with age, Analysis of covariance for both cholesterol and triglycerides showed highly significant treatment effects, but no stage effects and no stage-treatment interactions. It showed that the pretreatment value is of extreme importance for predicting or explaining the 3-month value. Death rates were calculated by level of pretreatment cholesterol or pretreatment triglycerides for all Stage II and IV patients, all treatments combined, and for Study 2 and Study 3 separately. No consistent trends were evident for cholesterol. Spearman correlation coefficients between category of initial triglyceride value and rank of death rate were computed to test for a quadratic effect. When the absolute values of the initial triglyceride values minus the overall mean were correlated with the death rate, a significant negative correlation was found for all causes of death and for deaths due to cardiovascular disease and prostatic cancer. These results indicate that the death rate is highest near the overal mean for initial triglyceride values and decreases as the initial values deviate above or below the mean. Initial triglyceride levels appear to have potential as indicators of risk of death in patients with prostatic cancer. The percentage of patients dead at 1 year by initial triglyceride levels, measured only in Study 3, revealed a pattern similar to that observed for the death rate, that is, the highest percentages were associated with values near the overall mean.", "contents": "Response of serum cholesterol and triglycerides to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer. Cholesterol and triglycerides were measured in plasma samples from patient with cancer of the prostate before and after 3 months treatment with either Premarin, Provera, Provera and diethylstilbestrol, or diethylstilbestrol alone. Cholesterol was also measured before and after one of three doses of diethylstilbestrol or placebo. Pretreatment cholesterol levels at 196 +/- 1.3 mg per 100 ml (X +/- SE, N = 1093) were significantly lower than these reported for similar age group noncancer controls. Significant increases occurred with some of the estrogen treatments. Pretreatment cholesterol levels showed a significant negative correlation with age in Stage III and IV patients of both studies and a positive correlation with hemoglobin in Stage III patients of both studies. Pretreatment triglyceride levels at 120 +/- 1.9 mg per 100 ml (X +/- SE, N = 1089) were similar to levels reported for noncancer controls of similar age. Estrogen treatment produced a significant increase in triglyceride levels. Serum triglycerides were significantly correlated with hemoglobin, weight, and cholesterol and negatively correlated with age, Analysis of covariance for both cholesterol and triglycerides showed highly significant treatment effects, but no stage effects and no stage-treatment interactions. It showed that the pretreatment value is of extreme importance for predicting or explaining the 3-month value. Death rates were calculated by level of pretreatment cholesterol or pretreatment triglycerides for all Stage II and IV patients, all treatments combined, and for Study 2 and Study 3 separately. No consistent trends were evident for cholesterol. Spearman correlation coefficients between category of initial triglyceride value and rank of death rate were computed to test for a quadratic effect. When the absolute values of the initial triglyceride values minus the overall mean were correlated with the death rate, a significant negative correlation was found for all causes of death and for deaths due to cardiovascular disease and prostatic cancer. These results indicate that the death rate is highest near the overal mean for initial triglyceride values and decreases as the initial values deviate above or below the mean. Initial triglyceride levels appear to have potential as indicators of risk of death in patients with prostatic cancer. The percentage of patients dead at 1 year by initial triglyceride levels, measured only in Study 3, revealed a pattern similar to that observed for the death rate, that is, the highest percentages were associated with values near the overall mean."} {"id": "PMID:182348", "title": "Response of plasma fibrinogen and plasminogen to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer.", "content": "Fibrinogen and plasminogen were measured in plasma samples from prostatic cancer patients before and after 3 months of treatment with either Premarin, Provera, Provera and diethylstilbestrol, one of three doses of diethylstilbestrol, or placebo. Plasminogen levels generally were increased significantly with the estrogens but were unchanged following placebo or Provera treatment. Pretreatment plasminogen levels in Study 3 were significantly lower (p less than .001) than in Study 2. Plasminogen pretreatment levels were significantly correlated with age, hemoglobin, body weight, and blood pressure. Fibrinogen pretreatment levels were significantly elevated above normal. They were not significantly with age, hemoglobin, body weight, or blood pressure. Fibrinogen levels generally were significantly decreased by the estrogens. Comparisons of means of pretreatment fibrinogen and plasminogen levels from patients dying during the first year of the study with the mean pretreatment levels of the patient group alive after 1 year on study yielded no significant differences. Death rates were calculated by pretreatment plasminogen or fibrinogen for all treatments of all Stage III and Stage IV patients combined for Study 2 and Study 3 separately. Such rates were calculated for all causes combined and for deaths from prostatic cancer or cardiovascular disease separately. The levels of plasminogen were significnatly negatively correlated with death rate from all causes combined and with cardiovascular disease considered separately, but not with death from prostatic cancer. The levels of fibrinogen were signigicantly positively correlated with death rates from all cuses and nearly significantly with prostatic cancer, but not cardiovascular disease. Elvated pretreatment fibrinogen levels were associated with an increased proportion of deaths at 1 year from all causes and from cancer of the prostate.", "contents": "Response of plasma fibrinogen and plasminogen to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer. Fibrinogen and plasminogen were measured in plasma samples from prostatic cancer patients before and after 3 months of treatment with either Premarin, Provera, Provera and diethylstilbestrol, one of three doses of diethylstilbestrol, or placebo. Plasminogen levels generally were increased significantly with the estrogens but were unchanged following placebo or Provera treatment. Pretreatment plasminogen levels in Study 3 were significantly lower (p less than .001) than in Study 2. Plasminogen pretreatment levels were significantly correlated with age, hemoglobin, body weight, and blood pressure. Fibrinogen pretreatment levels were significantly elevated above normal. They were not significantly with age, hemoglobin, body weight, or blood pressure. Fibrinogen levels generally were significantly decreased by the estrogens. Comparisons of means of pretreatment fibrinogen and plasminogen levels from patients dying during the first year of the study with the mean pretreatment levels of the patient group alive after 1 year on study yielded no significant differences. Death rates were calculated by pretreatment plasminogen or fibrinogen for all treatments of all Stage III and Stage IV patients combined for Study 2 and Study 3 separately. Such rates were calculated for all causes combined and for deaths from prostatic cancer or cardiovascular disease separately. The levels of plasminogen were significnatly negatively correlated with death rate from all causes combined and with cardiovascular disease considered separately, but not with death from prostatic cancer. The levels of fibrinogen were signigicantly positively correlated with death rates from all cuses and nearly significantly with prostatic cancer, but not cardiovascular disease. Elvated pretreatment fibrinogen levels were associated with an increased proportion of deaths at 1 year from all causes and from cancer of the prostate."} {"id": "PMID:182349", "title": "Early assessment of normal tissue tolerance of fast neutron beam radiation therapy.", "content": "Between September 10, 1973 and May 20, 1975, 94 selected patients were treated with fast neutron beams generated by bombarding an \"intermediate\" beryllium target with 21 MeV deuterons. The clinical material included: 58 patients with head and neck cancers; 27 patients with cerebral glioblastoma multiforme; and 9 patients with a variety of other neoplasms. Of the 67 patients treated only with neutron beams, 31 received two increments per week and 36 received three increments per week. The calculated doses in most patients were 1800 rad n gamma (neutrons + gamma components) delivered in 6 weeks. Seventeen patients were treated with two increments of neutron beams and three increments of 60Co photons weekly to calculated total doses of 780-1050 rad n gamma + 3360-3780 rad 60Co gamma delivered over 50-54 days. Ten patients were treated with neutron bean \"boosts\" of 300-900 rad n gamma in three to seven increments over 8-23 days following conventional radiation therapy. Treatment has been well tolerated, with only 9 of 94 patients not completing the anticipated course. In three of these, treatment was dixcontinued because of intercurrent problems. Except for those patients with glioblastoma multiforme, treatment complications have not been dose-related. In four patients, complications probably were related to persistent cancer. Neutron beam irradiaiton may have been a factor in the neurologic deterioration of five patients with glioblastoma multiforme who did not complete treatment.", "contents": "Early assessment of normal tissue tolerance of fast neutron beam radiation therapy. Between September 10, 1973 and May 20, 1975, 94 selected patients were treated with fast neutron beams generated by bombarding an \"intermediate\" beryllium target with 21 MeV deuterons. The clinical material included: 58 patients with head and neck cancers; 27 patients with cerebral glioblastoma multiforme; and 9 patients with a variety of other neoplasms. Of the 67 patients treated only with neutron beams, 31 received two increments per week and 36 received three increments per week. The calculated doses in most patients were 1800 rad n gamma (neutrons + gamma components) delivered in 6 weeks. Seventeen patients were treated with two increments of neutron beams and three increments of 60Co photons weekly to calculated total doses of 780-1050 rad n gamma + 3360-3780 rad 60Co gamma delivered over 50-54 days. Ten patients were treated with neutron bean \"boosts\" of 300-900 rad n gamma in three to seven increments over 8-23 days following conventional radiation therapy. Treatment has been well tolerated, with only 9 of 94 patients not completing the anticipated course. In three of these, treatment was dixcontinued because of intercurrent problems. Except for those patients with glioblastoma multiforme, treatment complications have not been dose-related. In four patients, complications probably were related to persistent cancer. Neutron beam irradiaiton may have been a factor in the neurologic deterioration of five patients with glioblastoma multiforme who did not complete treatment."} {"id": "PMID:182350", "title": "Humoral immunity to herpes simplex viral-induced antigens in smokers.", "content": "Antibodies to herpes simplex viral-induced antigens (HSVIA) were assayed by an indirect immunofluorescent technique in 93 regular cigarette smokers, 75 of whom also imbibed alcoholic beverages. Controls were 94 nonsmoking, nondrinking volunteers matched with the smoker for age and sex. IgA antibodies to HSVIA were detected six times more frequently in the sera of smokers than in nonsmoking controls, p less than .0005. IgG and IgM anti-HSVIA were detected with comparable frequencies in both groups, but the antibody titers were significantly higher in the smoking group than in controls, p less than .05. IgA anti-HSVIA was detected more frequently in smokers with 10 or more pack-years of cigarette exposure than in smokers with 10 or more pack-years of smoking (p less than .05) or in matched nonsmokers (p less than .02). IgA antibody titers to HSVIA were significantly higher in cigarette smokers who drank alcoholic beverages than in smokers who did not drink, p less than .025. This study demonstrates that cigarette smoking and the use of alcoholic beverages are associated with heightened humoral immunity to HSV-induced antigens in a population at high risk for development of squamous cell carcinomas of the head and neck region.", "contents": "Humoral immunity to herpes simplex viral-induced antigens in smokers. Antibodies to herpes simplex viral-induced antigens (HSVIA) were assayed by an indirect immunofluorescent technique in 93 regular cigarette smokers, 75 of whom also imbibed alcoholic beverages. Controls were 94 nonsmoking, nondrinking volunteers matched with the smoker for age and sex. IgA antibodies to HSVIA were detected six times more frequently in the sera of smokers than in nonsmoking controls, p less than .0005. IgG and IgM anti-HSVIA were detected with comparable frequencies in both groups, but the antibody titers were significantly higher in the smoking group than in controls, p less than .05. IgA anti-HSVIA was detected more frequently in smokers with 10 or more pack-years of cigarette exposure than in smokers with 10 or more pack-years of smoking (p less than .05) or in matched nonsmokers (p less than .02). IgA antibody titers to HSVIA were significantly higher in cigarette smokers who drank alcoholic beverages than in smokers who did not drink, p less than .025. This study demonstrates that cigarette smoking and the use of alcoholic beverages are associated with heightened humoral immunity to HSV-induced antigens in a population at high risk for development of squamous cell carcinomas of the head and neck region."} {"id": "PMID:182351", "title": "Trophoblastic pseudotumor of the uterus: an exaggerated form of \"syncytial endometritis\" simulating a malignant tumor.", "content": "Twelve cases of a hitherto unrecognized pseudotumorous trophoblastic invasion of the myometrium are analyzed. Human chorionic gonadotropin (HCG) was identified by an immunoenzyme technique in the cytoplasm of the invasive cells. The lesion may be localized and only superficially invasive or deeply invasive and have a gross appearance suggesting a neoplasm in the excised uterus. In either case, this process has been confused with various types of malignant tumors, most often choriocarcinoma, from which it may be distinguished by an absence of the characteristic dimorphic population of cytotrophoblast and cyncytiotrophoblast. Most of the patients, who ranged in age from 19 to 41 years, presented with amenorrhea uterine enlargement and were thought to be pregnant, although only four of them had positive pregnancy tests. The most serious complication was uterine perforation, which occurred spontaneously in one patient and during curettage in five others. One patient died as a result, but the other 11 are alive without evidence of disase 6 months to 12 years after the diagnosis. Of the 11 surviving patients, four received no treatment other than curettage. Because this trophoblastic lesion is likely benign and simulates a malignant tumor on pathologic examination, the term \"trophoblastic pseudotumor\" has been chosen to designate it.", "contents": "Trophoblastic pseudotumor of the uterus: an exaggerated form of \"syncytial endometritis\" simulating a malignant tumor. Twelve cases of a hitherto unrecognized pseudotumorous trophoblastic invasion of the myometrium are analyzed. Human chorionic gonadotropin (HCG) was identified by an immunoenzyme technique in the cytoplasm of the invasive cells. The lesion may be localized and only superficially invasive or deeply invasive and have a gross appearance suggesting a neoplasm in the excised uterus. In either case, this process has been confused with various types of malignant tumors, most often choriocarcinoma, from which it may be distinguished by an absence of the characteristic dimorphic population of cytotrophoblast and cyncytiotrophoblast. Most of the patients, who ranged in age from 19 to 41 years, presented with amenorrhea uterine enlargement and were thought to be pregnant, although only four of them had positive pregnancy tests. The most serious complication was uterine perforation, which occurred spontaneously in one patient and during curettage in five others. One patient died as a result, but the other 11 are alive without evidence of disase 6 months to 12 years after the diagnosis. Of the 11 surviving patients, four received no treatment other than curettage. Because this trophoblastic lesion is likely benign and simulates a malignant tumor on pathologic examination, the term \"trophoblastic pseudotumor\" has been chosen to designate it."} {"id": "PMID:182352", "title": "Direct immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase in human tumor tissues.", "content": "Immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase was performed on cryostat sections of five human tumor tisssues. With a direct immunoperoxidase staining for the localization of Regan isoenzyme at the light and electron microscope levels, sections previously fixed with 0.05 M phosphate-buffered 4% paraformaldehyde were reacted with rabbit antisera to human placenta alkaline phosphatase conjugated to horseradish peroxidase. Comparison of conventional histochemistry and immunohistochemistry for Regan isoenzyme indicated that strong specific immunoperoxidase staining appeared on the cell membrane surface, and a diffuse one, in the cytoplasm of lung and colon cancer tissue cells showing L-phenylalanine-sensitive alkaline phosphatase. No immunoperoxidase reaction was obtained in tumor cells showing sensitivity to L-homoarginine or lacking aklaline phosphatase activity.", "contents": "Direct immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase in human tumor tissues. Immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase was performed on cryostat sections of five human tumor tisssues. With a direct immunoperoxidase staining for the localization of Regan isoenzyme at the light and electron microscope levels, sections previously fixed with 0.05 M phosphate-buffered 4% paraformaldehyde were reacted with rabbit antisera to human placenta alkaline phosphatase conjugated to horseradish peroxidase. Comparison of conventional histochemistry and immunohistochemistry for Regan isoenzyme indicated that strong specific immunoperoxidase staining appeared on the cell membrane surface, and a diffuse one, in the cytoplasm of lung and colon cancer tissue cells showing L-phenylalanine-sensitive alkaline phosphatase. No immunoperoxidase reaction was obtained in tumor cells showing sensitivity to L-homoarginine or lacking aklaline phosphatase activity."} {"id": "PMID:182353", "title": "Primary mucinous adenocarcinoma of thyroid gland.", "content": "A mucin-producing carcinoma in the thyroid gland found in a 44-year-old man was first thought to be a metastatic carcinoma, possibly from salivary gland. However, follow-up examinations for 8 years have not demonstrated another neoplasm, and it seems reasonable to conclude that this lesion was a rare primary mucinous adenocarcinoma of the thyroid gland.", "contents": "Primary mucinous adenocarcinoma of thyroid gland. A mucin-producing carcinoma in the thyroid gland found in a 44-year-old man was first thought to be a metastatic carcinoma, possibly from salivary gland. However, follow-up examinations for 8 years have not demonstrated another neoplasm, and it seems reasonable to conclude that this lesion was a rare primary mucinous adenocarcinoma of the thyroid gland."} {"id": "PMID:182354", "title": "Risk and prognostic factors in trophoblastic neoplasia.", "content": "Three hundred and seventeen patients with gestational trophoblastic tumors were investigated and treated between 1957-1973. The risk of trophoblastic tumor was influenced by the outcome of the antecedent pregnancy (hydatidiform mole, non-mole abortion, term delivery) and the ABO blood groups of the mating couple; it was also influenced by the patient's age. The response to treatment with chemotherapy and , where appropriate, with surgery and radiotherapy, was influenced prfoundly by several factors. These included 1) the outcome of the antecedent pregnancy, 2) the total body burden of tumor at the time treatment stated as reflected by the urinary output of human chorionic gonadotrophin (CG), 3) the interval between the antecedent pregnancy and the start of chemotherapy, 4) the ABO groups of the mating couple, 5) the extent of mononuclear cell infiltration in the tumor, 6) the immunological status of the patient at the start of treatment, 7) the size of tumor masses, 8) the site of metastases and particularly the presence of intracranial metastases, and possibly by 9) the age and 10) the parity of the patient. A detailed study of the HLA antigens of the patient, her husband, and antecedent child has shown no positive effect on risk or prognosis. These data provide a basis for a scoring system that allows the prognosis to be defined at the time of diagnosis and facilitates tisk of drug resistance. Applied retrospectively to the cases from which the scoring system was generated, prognostic groups with survival rates ranging from 0-100% can be defined. Unfavorable prognostic factors combine so as to increase the probability of drug resistance.", "contents": "Risk and prognostic factors in trophoblastic neoplasia. Three hundred and seventeen patients with gestational trophoblastic tumors were investigated and treated between 1957-1973. The risk of trophoblastic tumor was influenced by the outcome of the antecedent pregnancy (hydatidiform mole, non-mole abortion, term delivery) and the ABO blood groups of the mating couple; it was also influenced by the patient's age. The response to treatment with chemotherapy and , where appropriate, with surgery and radiotherapy, was influenced prfoundly by several factors. These included 1) the outcome of the antecedent pregnancy, 2) the total body burden of tumor at the time treatment stated as reflected by the urinary output of human chorionic gonadotrophin (CG), 3) the interval between the antecedent pregnancy and the start of chemotherapy, 4) the ABO groups of the mating couple, 5) the extent of mononuclear cell infiltration in the tumor, 6) the immunological status of the patient at the start of treatment, 7) the size of tumor masses, 8) the site of metastases and particularly the presence of intracranial metastases, and possibly by 9) the age and 10) the parity of the patient. A detailed study of the HLA antigens of the patient, her husband, and antecedent child has shown no positive effect on risk or prognosis. These data provide a basis for a scoring system that allows the prognosis to be defined at the time of diagnosis and facilitates tisk of drug resistance. Applied retrospectively to the cases from which the scoring system was generated, prognostic groups with survival rates ranging from 0-100% can be defined. Unfavorable prognostic factors combine so as to increase the probability of drug resistance."} {"id": "PMID:182355", "title": "Management of small cell carcinoma of the lung: therapy, staging, and biochemical markers.", "content": "A chemotherapeutic regimen consisting of BCNU, cyclophosphamide, vincristine, and procarbazine was evaluated in 43 patients with small cell carcinoma of the lung. The majority of patients received radiation therapy of the primary tumor, but chemotherapy alone was utilized in a group of patients with widely disseminated disease. In addition to thorough staging with radioisotope scans and bone marrow biopsies, a study of calcitonin and histaminase as biochemical markers was performed. The BCVP chemotherapy resulted in a complete and partial response rate of 53% when given alone or in conjunction with radiotherapy. The survival data are preliminary, but the complete responders do have a statistically significant better survival (mean of + -95 days) than the partial responders and nonresponders. Hypercalcitonemia was not detected in our patients, but elevated histaminase activity was found in eight of 24 patients with small cell carcinoma and in only one of 19 patients with squamous and large cell carcinoma.", "contents": "Management of small cell carcinoma of the lung: therapy, staging, and biochemical markers. A chemotherapeutic regimen consisting of BCNU, cyclophosphamide, vincristine, and procarbazine was evaluated in 43 patients with small cell carcinoma of the lung. The majority of patients received radiation therapy of the primary tumor, but chemotherapy alone was utilized in a group of patients with widely disseminated disease. In addition to thorough staging with radioisotope scans and bone marrow biopsies, a study of calcitonin and histaminase as biochemical markers was performed. The BCVP chemotherapy resulted in a complete and partial response rate of 53% when given alone or in conjunction with radiotherapy. The survival data are preliminary, but the complete responders do have a statistically significant better survival (mean of + -95 days) than the partial responders and nonresponders. Hypercalcitonemia was not detected in our patients, but elevated histaminase activity was found in eight of 24 patients with small cell carcinoma and in only one of 19 patients with squamous and large cell carcinoma."} {"id": "PMID:182356", "title": "Recurrent cystosarcoma phyllodes: a clinicopathologic study of 32 cases.", "content": "A retrospective study was made of recurrent mammary cystosarcoma phyllodes seen at Memorial Sloan-Kettering Cancer Center from 1932 to 1972. Clinicopathologic findings, clinical course, treatment, and survival are described. It is apparent that cystosarcomas may recur and several years may elapse between reucrrences. We found that 18% of the benign and 8% of the malignant cystosarcomas recurred and malignant \"transformation\" occurred in two of the 28 recurrent benign cystosarcomas.", "contents": "Recurrent cystosarcoma phyllodes: a clinicopathologic study of 32 cases. A retrospective study was made of recurrent mammary cystosarcoma phyllodes seen at Memorial Sloan-Kettering Cancer Center from 1932 to 1972. Clinicopathologic findings, clinical course, treatment, and survival are described. It is apparent that cystosarcomas may recur and several years may elapse between reucrrences. We found that 18% of the benign and 8% of the malignant cystosarcomas recurred and malignant \"transformation\" occurred in two of the 28 recurrent benign cystosarcomas."} {"id": "PMID:182357", "title": "Pretranslational control of tryptophan oxygenase levels in Morris hepatoma and host liver.", "content": "Tryptophan oxygenase is present and hormonally inducible in host livers but is absent in transplanted Morris hepatomas examined under basal conditions as well as in hormonally induced animals. Studies were performed to determine whether the absence of tryptophan oxygenase in hepatomas is mediated by an alteration in the translational efficiency or the level of the messenger RNA (mRNA) for tryptophan oxygenase. The tissue level of the specific mRNA coding for tryptophan oxygenase was quantitated in an mRNA-dependent Krebs ascites cell-free protein-synthesizing system. The enzyme levels and mRNA activities in host livers and hepatomas from control rats and rats given injections of an inducing dose of hydrocortisone were compared; they indicate that the induction of tryptophan oxygenase in host livers by hormones is accompanied by a proportional increase in the level of its mRNA, whereas in the transplanted hepatomas the tryptophan oxygenase catalytic activity and the mRNA coding for this enzyme were undetectable in both control and glucocorticoid-induced animals. No functional mRNA for tryptophan oxygenase could be detected in the total polyadenylate-containing mRNA isolated from the Morris hepatoma cells. The hepatomas contained normal levels of cytoplasmic glucocorticoid receptor that could bind glucocorticoid, undergo \"activation,\" and translocate to both normal and neoplastic nuclei. Thus, deletion of tryptophan oxygenase in hepatomas is a consequence of the absence of the gene product, i.e., the tryptophan oxygenase mRNA, which codes for its synthesis; this is not due to detectable alterations in the ability of the glucocorticoid receptor to bind the steroid hormone, or of the hormone-receptor complex to undergo activation, or of the activated steroid-receptor complex to bind to nuclei derived from the hepatoma or normal liver.", "contents": "Pretranslational control of tryptophan oxygenase levels in Morris hepatoma and host liver. Tryptophan oxygenase is present and hormonally inducible in host livers but is absent in transplanted Morris hepatomas examined under basal conditions as well as in hormonally induced animals. Studies were performed to determine whether the absence of tryptophan oxygenase in hepatomas is mediated by an alteration in the translational efficiency or the level of the messenger RNA (mRNA) for tryptophan oxygenase. The tissue level of the specific mRNA coding for tryptophan oxygenase was quantitated in an mRNA-dependent Krebs ascites cell-free protein-synthesizing system. The enzyme levels and mRNA activities in host livers and hepatomas from control rats and rats given injections of an inducing dose of hydrocortisone were compared; they indicate that the induction of tryptophan oxygenase in host livers by hormones is accompanied by a proportional increase in the level of its mRNA, whereas in the transplanted hepatomas the tryptophan oxygenase catalytic activity and the mRNA coding for this enzyme were undetectable in both control and glucocorticoid-induced animals. No functional mRNA for tryptophan oxygenase could be detected in the total polyadenylate-containing mRNA isolated from the Morris hepatoma cells. The hepatomas contained normal levels of cytoplasmic glucocorticoid receptor that could bind glucocorticoid, undergo \"activation,\" and translocate to both normal and neoplastic nuclei. Thus, deletion of tryptophan oxygenase in hepatomas is a consequence of the absence of the gene product, i.e., the tryptophan oxygenase mRNA, which codes for its synthesis; this is not due to detectable alterations in the ability of the glucocorticoid receptor to bind the steroid hormone, or of the hormone-receptor complex to undergo activation, or of the activated steroid-receptor complex to bind to nuclei derived from the hepatoma or normal liver."} {"id": "PMID:182358", "title": "Levels of C-type viral p30 antigens in lymphoma-resistant mice.", "content": "Until relatively recently, interest has largely centered upon the causal role of oncogenic viruses especially with respect to the development of murine lymphomas. Host factors have recently come to the fore and are considered to be effective here, where we note that, in spite of relatively high levels of C-type viral antigen in the AKR X CBA F1 mouse, this hybrid remains relatively lymphoma resistant. Evidence points to an overriding host factor in this situation that is dominant with respect to tumor resistance and furthermore independent of the viral load at least as judged by levels of p30 viral antigen, an assumption confirmed by xc plaque assay.", "contents": "Levels of C-type viral p30 antigens in lymphoma-resistant mice. Until relatively recently, interest has largely centered upon the causal role of oncogenic viruses especially with respect to the development of murine lymphomas. Host factors have recently come to the fore and are considered to be effective here, where we note that, in spite of relatively high levels of C-type viral antigen in the AKR X CBA F1 mouse, this hybrid remains relatively lymphoma resistant. Evidence points to an overriding host factor in this situation that is dominant with respect to tumor resistance and furthermore independent of the viral load at least as judged by levels of p30 viral antigen, an assumption confirmed by xc plaque assay."} {"id": "PMID:182359", "title": "Differences in transcription between transformed mouse cells in culture and the tumors that they produce in syngeneic mice.", "content": "RNA-DNA saturation hybridization experiments were used to determine the degree to which cellular DNA sequences are transcribed in cultured mouse cells transformed by polyoma virus and in tumors that develop after injection of these cells into syngeneic mice. A general, overall reduction in the proportion of the genome transcribed was found in tumors compared to the proportion in cultured transformed cells. When explants of the tumor cells were grown in culture, the level of transcription of both repetitive and nonrepetitive DNA returned to that observed in the original transformed cells.", "contents": "Differences in transcription between transformed mouse cells in culture and the tumors that they produce in syngeneic mice. RNA-DNA saturation hybridization experiments were used to determine the degree to which cellular DNA sequences are transcribed in cultured mouse cells transformed by polyoma virus and in tumors that develop after injection of these cells into syngeneic mice. A general, overall reduction in the proportion of the genome transcribed was found in tumors compared to the proportion in cultured transformed cells. When explants of the tumor cells were grown in culture, the level of transcription of both repetitive and nonrepetitive DNA returned to that observed in the original transformed cells."} {"id": "PMID:182360", "title": "Immunization against feline oncarnavirus disease using a killed tumor cell vaccine.", "content": "Specific pathogen-free cats were immunized with an inactivated feline oncornavirus tumor cell vaccine. Immunized cats produced high antibody titers to the feline oncornavirus-associated cell membrane antigen and were protected from oncogenic feline sarcoma virus challenge. However, immunization did not produce virus-neutralizing antibody nor did it prevent viremia.", "contents": "Immunization against feline oncarnavirus disease using a killed tumor cell vaccine. Specific pathogen-free cats were immunized with an inactivated feline oncornavirus tumor cell vaccine. Immunized cats produced high antibody titers to the feline oncornavirus-associated cell membrane antigen and were protected from oncogenic feline sarcoma virus challenge. However, immunization did not produce virus-neutralizing antibody nor did it prevent viremia."} {"id": "PMID:182361", "title": "Binding of metabolically activated benzo(a)pyrene to nuclear macromolecules.", "content": "The binding of metabolically activated [3H]benzo(a)pyrene ([3H]BP) to the DNA, RNA, histones, and nonhistones of isolated rat liver and lung nuclei was studied. Conditions for optimal binding to the nuclear components were determined. Upon incubation with isolated liver nuclei and reduced nicotinamide adenine dinucleotide phosphate, [3H]BP was able to bind to nuclear components. The binding appeared to be covalent in nature. Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also increased the level of carcinogen binding. The addition of rat liver microsomes to the incubation systems greatly enhanced the level of [3H]BP binding to the macromolecules in the nuclei from both the control and 3-methylcholanthrene-treated rats, and the maximal levels of binding obtained with these two types of nuclei were similar. The binding was inhibited by 7,8-benzoflavone or glutathione. Lung nuclei from control rats had very low AHH activity and did not exhibit appreciable carcinogen binding, whereas those from 3-methylcholanthrene-pretreated animals had slightly higher AHH activity and caused low levels of binding. The binding of [3H]BP to lung nuclei was greatly enhanced by liver microsomes but only slightly by lung microsomes, which had rather low AHH activity. Several lines of evidence indicate that, in the control experiments (no reduced nicotinamide adenine dinucleotide phosphate added), the radioactivity associated with the macromolecule fractions is probably a background value rather than due to the binding caused by a specific interaction between benzo(a)pyrene and cytochrome P-450. The present study clearly demonstrates that a carcinogen activated at the microsomes can enter into the nucleus and react with its macromolecules; the carcinogen can also be activated by the monoxygenase system of the nuclear envelope. It appears that both the endoplasmic reticulum and the nuclear envelope are potentially important sites of carcinogen activation.", "contents": "Binding of metabolically activated benzo(a)pyrene to nuclear macromolecules. The binding of metabolically activated [3H]benzo(a)pyrene ([3H]BP) to the DNA, RNA, histones, and nonhistones of isolated rat liver and lung nuclei was studied. Conditions for optimal binding to the nuclear components were determined. Upon incubation with isolated liver nuclei and reduced nicotinamide adenine dinucleotide phosphate, [3H]BP was able to bind to nuclear components. The binding appeared to be covalent in nature. Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also increased the level of carcinogen binding. The addition of rat liver microsomes to the incubation systems greatly enhanced the level of [3H]BP binding to the macromolecules in the nuclei from both the control and 3-methylcholanthrene-treated rats, and the maximal levels of binding obtained with these two types of nuclei were similar. The binding was inhibited by 7,8-benzoflavone or glutathione. Lung nuclei from control rats had very low AHH activity and did not exhibit appreciable carcinogen binding, whereas those from 3-methylcholanthrene-pretreated animals had slightly higher AHH activity and caused low levels of binding. The binding of [3H]BP to lung nuclei was greatly enhanced by liver microsomes but only slightly by lung microsomes, which had rather low AHH activity. Several lines of evidence indicate that, in the control experiments (no reduced nicotinamide adenine dinucleotide phosphate added), the radioactivity associated with the macromolecule fractions is probably a background value rather than due to the binding caused by a specific interaction between benzo(a)pyrene and cytochrome P-450. The present study clearly demonstrates that a carcinogen activated at the microsomes can enter into the nucleus and react with its macromolecules; the carcinogen can also be activated by the monoxygenase system of the nuclear envelope. It appears that both the endoplasmic reticulum and the nuclear envelope are potentially important sites of carcinogen activation."} {"id": "PMID:182362", "title": "Inhibition of antibody-complement-mediated killing of tumor cells by hormones.", "content": "Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated at 37 degrees with 10(-4) to 10(-11) M concentrations of the polypeptide hormone insulin, with the catecholamine L-epinephrine-HCl, or with the glucocorticoid steroids hydrocortisone sodium succinate or prednisolone sodium succinate, the cells show a marked reduction in their suseptibility to killing by antibody and guinea pig complement; pretreatment at 0 degrees is ineffective. Similar results were obtained with another antigenically distinct guinea pig hepatoma (line 10) when tested with anti-Forssman immuno-globulin M or specific antitumor antibodies and human complement. The ability of the hormones to render the cells resistant is dependent on time, temperature, and hormone concentration. The effect of hormone treatment is maximal between 30 and 60 min and is reversible within 4 hr even in the continued presence of hormone. Treatment of line 1 cells with up to 10,000-fold greater concentrations of the less biologically active or inactive analogs, DL-epinephrine, beta-estradiol, testosterone, or proinsulin has no effect on the susceptibility of the cells to killing by antibody and guinea pig complement. The effect of hormone treatment is not due to a direct inactivation of bound or fluid-phase complement components by the hormones or to a decrease in the ability of the cells to bind complement-fixing antibody.", "contents": "Inhibition of antibody-complement-mediated killing of tumor cells by hormones. Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated at 37 degrees with 10(-4) to 10(-11) M concentrations of the polypeptide hormone insulin, with the catecholamine L-epinephrine-HCl, or with the glucocorticoid steroids hydrocortisone sodium succinate or prednisolone sodium succinate, the cells show a marked reduction in their suseptibility to killing by antibody and guinea pig complement; pretreatment at 0 degrees is ineffective. Similar results were obtained with another antigenically distinct guinea pig hepatoma (line 10) when tested with anti-Forssman immuno-globulin M or specific antitumor antibodies and human complement. The ability of the hormones to render the cells resistant is dependent on time, temperature, and hormone concentration. The effect of hormone treatment is maximal between 30 and 60 min and is reversible within 4 hr even in the continued presence of hormone. Treatment of line 1 cells with up to 10,000-fold greater concentrations of the less biologically active or inactive analogs, DL-epinephrine, beta-estradiol, testosterone, or proinsulin has no effect on the susceptibility of the cells to killing by antibody and guinea pig complement. The effect of hormone treatment is not due to a direct inactivation of bound or fluid-phase complement components by the hormones or to a decrease in the ability of the cells to bind complement-fixing antibody."} {"id": "PMID:182363", "title": "Inhibition of de novo pyrimidine nucleotide and DNA synthesis and growth of cultured Novikoff rat hepatoma cells and other cell lines by pyrazofurin (NSC 143095).", "content": "Pyrazofurin (PYF), a C-riboside, inhibited the replication of cultured Novikoff rat hepatoma cells, HeLa cells, and mouse L-cells at concentrations as low as 0.1 to 10 muM, but Novikoff cells were more sensitive than the cells of the other two cell lines. Inhibition of cell replication was completely prevented by the presence of 0.1 to 1 mM uridine in the medium, and partly by the presence of other pyrimidine, but not purine nucleosides. A 2- to 4-hr treatment of the cells with 10 muM PYF resulted in a 2-fold increase in the rate of incorporation of uridine into the acid-soluble pool and nucleic acids, while the rate of incorporation of adenosine into RNA was reduced about 85%. The incorporation of adenosine and deoxyuridine into DNA were reduced about 85 and 50%, respectively. The results are consistent with the view that PYF inhibits the de novo synthesis of pyrimidine nucleosides. The inhibition of cell replication seems to be due mainly to an inhibition of DNA rather than RNA synthesis, resulting from a rapid depletion of the pyrimidine deoxynucleotide pool, since addition of thymidine and deoxycytidine reversed the inhibition of DNA synthesis and cell replication by PYF. PYF must enter the cells to exert its toxicity since the toxicity of PYF was reduced 70 to 80% by the presence of 8 muM Persantin, a potent inhibitor of the facilitated and simple diffusion of various substrates, in the medium. If PYF is incorporated via normal nucleoside salvage pathways, its affinity for the nucleoside transport system(s) and kinases, must be low since, even at a concentration of 1 mM, it had only a slight effect on the initial rates of incorporation of various nucleosides into the nucleotide pool.", "contents": "Inhibition of de novo pyrimidine nucleotide and DNA synthesis and growth of cultured Novikoff rat hepatoma cells and other cell lines by pyrazofurin (NSC 143095). Pyrazofurin (PYF), a C-riboside, inhibited the replication of cultured Novikoff rat hepatoma cells, HeLa cells, and mouse L-cells at concentrations as low as 0.1 to 10 muM, but Novikoff cells were more sensitive than the cells of the other two cell lines. Inhibition of cell replication was completely prevented by the presence of 0.1 to 1 mM uridine in the medium, and partly by the presence of other pyrimidine, but not purine nucleosides. A 2- to 4-hr treatment of the cells with 10 muM PYF resulted in a 2-fold increase in the rate of incorporation of uridine into the acid-soluble pool and nucleic acids, while the rate of incorporation of adenosine into RNA was reduced about 85%. The incorporation of adenosine and deoxyuridine into DNA were reduced about 85 and 50%, respectively. The results are consistent with the view that PYF inhibits the de novo synthesis of pyrimidine nucleosides. The inhibition of cell replication seems to be due mainly to an inhibition of DNA rather than RNA synthesis, resulting from a rapid depletion of the pyrimidine deoxynucleotide pool, since addition of thymidine and deoxycytidine reversed the inhibition of DNA synthesis and cell replication by PYF. PYF must enter the cells to exert its toxicity since the toxicity of PYF was reduced 70 to 80% by the presence of 8 muM Persantin, a potent inhibitor of the facilitated and simple diffusion of various substrates, in the medium. If PYF is incorporated via normal nucleoside salvage pathways, its affinity for the nucleoside transport system(s) and kinases, must be low since, even at a concentration of 1 mM, it had only a slight effect on the initial rates of incorporation of various nucleosides into the nucleotide pool."} {"id": "PMID:182365", "title": "Nitrosourea combinations in lung cancer.", "content": "BCNU, CCNU, and methyl-CCNU have undergone extensive trial in multiple drug combinations for bronchogenic carcinoma. The addition of a nitrosourea appears to be an improvement over cyclophosphamide used alone in oat cell carcinoma and over the two drug combination of cyclophosphamide and methotrexate in both adenocarcinoma of the lung and oat cell disease. Encouraging response rates have been seen in squamous lung cancer with multiple-drug combinations of a nitrosourea, an alkylating agent, vincristine, and bleomycin with or without adriamycin. The nitrosoureas have been easily incorporated, at reduced doses, into multiple-drug regimens with cumulative myelosuppression seen only when the interval between nitrosourea doses is less than 6 weeks. Conclusions about the ultimate role of these compounds in lunb cancer treatment must await (a) comparative trials of combinations with and without a nitrosourea, and (b) further exploration of new approaches to increase their therapeutic index.", "contents": "Nitrosourea combinations in lung cancer. BCNU, CCNU, and methyl-CCNU have undergone extensive trial in multiple drug combinations for bronchogenic carcinoma. The addition of a nitrosourea appears to be an improvement over cyclophosphamide used alone in oat cell carcinoma and over the two drug combination of cyclophosphamide and methotrexate in both adenocarcinoma of the lung and oat cell disease. Encouraging response rates have been seen in squamous lung cancer with multiple-drug combinations of a nitrosourea, an alkylating agent, vincristine, and bleomycin with or without adriamycin. The nitrosoureas have been easily incorporated, at reduced doses, into multiple-drug regimens with cumulative myelosuppression seen only when the interval between nitrosourea doses is less than 6 weeks. Conclusions about the ultimate role of these compounds in lunb cancer treatment must await (a) comparative trials of combinations with and without a nitrosourea, and (b) further exploration of new approaches to increase their therapeutic index."} {"id": "PMID:182366", "title": "The incidence of premature contractions in coronary patients during the sleep-awake cycle.", "content": "Mean heart rates and their variability indices during REM sleep and the frequency of cardiac arrhythmias during the sleep-awake cycle were determined in a group of coronary patients with disturbances of cardiac rhythm. In some patients there was a temporal relationship of atrial and ventricular premature contractions with slow-wave sleep, REM sleep or wakefulness. However, when they were considered as a group, no significant correlation could be observed. Furthermore, the sinus arrhythmia characteristic of REM sleep was not found to be exaggerated in those patients.", "contents": "The incidence of premature contractions in coronary patients during the sleep-awake cycle. Mean heart rates and their variability indices during REM sleep and the frequency of cardiac arrhythmias during the sleep-awake cycle were determined in a group of coronary patients with disturbances of cardiac rhythm. In some patients there was a temporal relationship of atrial and ventricular premature contractions with slow-wave sleep, REM sleep or wakefulness. However, when they were considered as a group, no significant correlation could be observed. Furthermore, the sinus arrhythmia characteristic of REM sleep was not found to be exaggerated in those patients."} {"id": "PMID:182367", "title": "Insulin: fundamental mechanism of action and the heart.", "content": "Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.", "contents": "Insulin: fundamental mechanism of action and the heart. Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate."} {"id": "PMID:182368", "title": "Differential beta adrenergic sensitivity of atrial and ventricular tissue assessed by chronotropic, inotropic, and cyclic AMP responses to isoprenaline and dobutamine.", "content": "Cat atrial tissue was more sensitive to isoprenaline (USP:isoproterenol) and dobutamine than ventricular tissue. Chronotropic response of atrial strips occurred at lower agonist concentrations than inotropic responses of papillary muscle. Cyclic AMP responses in atrial slices also occurred at lower agonist concentrations and were of much greater magnitude than the cyclic AMP responses in ventricular slices. However, the disporportionately greater sensitivity of atrial tissue was more marked with isoprenaline than with dobutamine.", "contents": "Differential beta adrenergic sensitivity of atrial and ventricular tissue assessed by chronotropic, inotropic, and cyclic AMP responses to isoprenaline and dobutamine. Cat atrial tissue was more sensitive to isoprenaline (USP:isoproterenol) and dobutamine than ventricular tissue. Chronotropic response of atrial strips occurred at lower agonist concentrations than inotropic responses of papillary muscle. Cyclic AMP responses in atrial slices also occurred at lower agonist concentrations and were of much greater magnitude than the cyclic AMP responses in ventricular slices. However, the disporportionately greater sensitivity of atrial tissue was more marked with isoprenaline than with dobutamine."} {"id": "PMID:182369", "title": "On the fine structure of the small, heavily pigmented non-pyramidal cells in lamina II and upper lamina III of the human isocortex.", "content": "With the aid of a newly developed technique for the successive examination of both the Golgi and pigment picture of individual neurons (Braak, 1974a) Braak (1974b) demonstrated that within lamina II and upper lamina III of the human isocortex, heavily pigmented non-pyramidal cells are distributed irregularly and sparsely. The lipofuscin pigment granules serve as excellent internal markers to identify these non-pyramidal cells in ultrathin sections. This favourable circumstance facilitates the study of these interneurons in the electron microscope. The heavily pigmented non-pyramidal cells are small, spherical to avoid with diameters of about 12-15 mum. One pole of the cell comprising a large cytoplasmic area gives rise to a few dendrites, while the other pole is occupied by the nucleus and in some cases is in close apposition to another nerve cell body. The nucleus is deeply invaginated by the large cytoplasmic area and occasionally displays nuclear inclusions. Among the usual organelles distributed within the large cytoplasmic area the mitochondria with a moderately electron dense matrix are abundant and the coarse lipofuscin pigment granules are the most striking elements. The latter contain densely packed filamentous or tubular material and a single vacuole. The perikaryon rarely receives more than 3 type I and type tii synapses per section per cell, whereas the dendrites receive numerous synapses of both type I and type II. Within the apposition zone to another nerve cell body (which in no case is a heavily pigmented non-pyramidal cell) puncta adhaerentia occur and also contacts in which the cleft of 8 nm is intersected by a dense stratum. Some of the ultrastructural findings are summarized in the schematic drawing of Figure 15.", "contents": "On the fine structure of the small, heavily pigmented non-pyramidal cells in lamina II and upper lamina III of the human isocortex. With the aid of a newly developed technique for the successive examination of both the Golgi and pigment picture of individual neurons (Braak, 1974a) Braak (1974b) demonstrated that within lamina II and upper lamina III of the human isocortex, heavily pigmented non-pyramidal cells are distributed irregularly and sparsely. The lipofuscin pigment granules serve as excellent internal markers to identify these non-pyramidal cells in ultrathin sections. This favourable circumstance facilitates the study of these interneurons in the electron microscope. The heavily pigmented non-pyramidal cells are small, spherical to avoid with diameters of about 12-15 mum. One pole of the cell comprising a large cytoplasmic area gives rise to a few dendrites, while the other pole is occupied by the nucleus and in some cases is in close apposition to another nerve cell body. The nucleus is deeply invaginated by the large cytoplasmic area and occasionally displays nuclear inclusions. Among the usual organelles distributed within the large cytoplasmic area the mitochondria with a moderately electron dense matrix are abundant and the coarse lipofuscin pigment granules are the most striking elements. The latter contain densely packed filamentous or tubular material and a single vacuole. The perikaryon rarely receives more than 3 type I and type tii synapses per section per cell, whereas the dendrites receive numerous synapses of both type I and type II. Within the apposition zone to another nerve cell body (which in no case is a heavily pigmented non-pyramidal cell) puncta adhaerentia occur and also contacts in which the cleft of 8 nm is intersected by a dense stratum. Some of the ultrastructural findings are summarized in the schematic drawing of Figure 15."} {"id": "PMID:182370", "title": "Cell differentiation of the fetal rat anterior pituitary in vitro.", "content": "Adenohypophysial primordia of rat embryos at 13 to 15 days gestation were cultured in Parker 199 synthetic medium for 2 to 11 days. At the end of the culture period their fine structure and the presence of immunoreactive trophic hormones using the peroxidase-labeled antibody technique were investigated. The degree of differentiation in the glands depends largely on the age of the embryos furnishing the explants. Cultured pituitaries explanted on the 13th day of gestation contain only ACTH-positive cells and about 15% of the cells are granular. The granules are 50-100 nm in diameter in some cells, while in other cells they range from 50 to 200 nm. In cultivated adenohypophysial primordia of embryos on the 15th day of intrauterine life ACTH, prolactin, LH and TSH cells are evident, but only the same two kinds of granular cells can be observed with the electron microscope. The extent of cytodifferentiation in the glands explanted on the 14th day of gestation is intermediate between the two other groups. The data suggest that the fetal rat pituitary has the capacity of self-differentiation but to a lesser extent than that of the in situ hypophysis.", "contents": "Cell differentiation of the fetal rat anterior pituitary in vitro. Adenohypophysial primordia of rat embryos at 13 to 15 days gestation were cultured in Parker 199 synthetic medium for 2 to 11 days. At the end of the culture period their fine structure and the presence of immunoreactive trophic hormones using the peroxidase-labeled antibody technique were investigated. The degree of differentiation in the glands depends largely on the age of the embryos furnishing the explants. Cultured pituitaries explanted on the 13th day of gestation contain only ACTH-positive cells and about 15% of the cells are granular. The granules are 50-100 nm in diameter in some cells, while in other cells they range from 50 to 200 nm. In cultivated adenohypophysial primordia of embryos on the 15th day of intrauterine life ACTH, prolactin, LH and TSH cells are evident, but only the same two kinds of granular cells can be observed with the electron microscope. The extent of cytodifferentiation in the glands explanted on the 14th day of gestation is intermediate between the two other groups. The data suggest that the fetal rat pituitary has the capacity of self-differentiation but to a lesser extent than that of the in situ hypophysis."} {"id": "PMID:182371", "title": "Multinucleate cells in thymus of C3H mice.", "content": "Multinucleate epithelial cells occur in the thymus of C3H mice. They are poorly differentiated and scarce, but are more numerous in the medulla than in the cortex. Their increase in number with age is particularly significant between the first and the third months especially for cells with a large number of nuclei, and may be related to thymic involution. Viral particles of type C, similar to those described in murine leukemias, are found in mono- and multinucleate medullary epithelial cells.", "contents": "Multinucleate cells in thymus of C3H mice. Multinucleate epithelial cells occur in the thymus of C3H mice. They are poorly differentiated and scarce, but are more numerous in the medulla than in the cortex. Their increase in number with age is particularly significant between the first and the third months especially for cells with a large number of nuclei, and may be related to thymic involution. Viral particles of type C, similar to those described in murine leukemias, are found in mono- and multinucleate medullary epithelial cells."} {"id": "PMID:182372", "title": "The influence of social rank on adenohypophysial cell activity in Salmo irideus. With special reference to basophil ACTH-cells of the proximal pars distalis.", "content": "In nine cell types of the adenohypophysis in untreated adult rainbow trout, histologically different activity phases, seasonal changes in activity, and the relation between certain cell types and the interrenal gland, thyroid or gonads were investigated by light and, occasionally, by electron microscopy. Special attention was given to the effect of social rank on the synthetic activity in adenohypophysial cells of trout kept in small groups in which a social hierarchy with one (light) dominant and several (dark) submissives is established. Cell types in the rostral pars distalis were azocarminophil (I) or amphiphil (II). Proximal pars distalis cell types were slightly basophil (IV), orangeophil (V), strongly basophil (VI) or chromophobe (VII). In the pars intermedia, cell types were amphiphil (VIII) or very slightly basophil (IX). Type III was a non-secretory supporting (?) cell. Histologically different activity phases abounded in type IV cells, which mainly occurred in the proximal pars distalis but were also found dispersed in the rostral pars distalis, the pars intermedia and the neurohypophysis. Influences of social rank were pronounced in type IV cells. Phases with a high synthetic activity were exclusively found in submissive animals, phases with a low synthetic activity occurred in dominants. As a positive relation existed between type IV cell activity and the social rank dependent activity of the interrenal gland, it was suggested that type IV cells produce ACTH. In (dominant) male trout treated with DOCG or ACTH, colloid-containing type IV cell phases, reflecting accumulation of the secretory product, were found. This supported the earlier suggestion that ACTH in the trout is produced in the basophil type IV cells and not, as reported in the literature, in cells comparable to type II.", "contents": "The influence of social rank on adenohypophysial cell activity in Salmo irideus. With special reference to basophil ACTH-cells of the proximal pars distalis. In nine cell types of the adenohypophysis in untreated adult rainbow trout, histologically different activity phases, seasonal changes in activity, and the relation between certain cell types and the interrenal gland, thyroid or gonads were investigated by light and, occasionally, by electron microscopy. Special attention was given to the effect of social rank on the synthetic activity in adenohypophysial cells of trout kept in small groups in which a social hierarchy with one (light) dominant and several (dark) submissives is established. Cell types in the rostral pars distalis were azocarminophil (I) or amphiphil (II). Proximal pars distalis cell types were slightly basophil (IV), orangeophil (V), strongly basophil (VI) or chromophobe (VII). In the pars intermedia, cell types were amphiphil (VIII) or very slightly basophil (IX). Type III was a non-secretory supporting (?) cell. Histologically different activity phases abounded in type IV cells, which mainly occurred in the proximal pars distalis but were also found dispersed in the rostral pars distalis, the pars intermedia and the neurohypophysis. Influences of social rank were pronounced in type IV cells. Phases with a high synthetic activity were exclusively found in submissive animals, phases with a low synthetic activity occurred in dominants. As a positive relation existed between type IV cell activity and the social rank dependent activity of the interrenal gland, it was suggested that type IV cells produce ACTH. In (dominant) male trout treated with DOCG or ACTH, colloid-containing type IV cell phases, reflecting accumulation of the secretory product, were found. This supported the earlier suggestion that ACTH in the trout is produced in the basophil type IV cells and not, as reported in the literature, in cells comparable to type II."} {"id": "PMID:182373", "title": "Temperature-sensitive mutants of Balb/3T3 cells: description of a mutant affected in cellular and polyoma virus DNA synthesis.", "content": "A temperature-sensitive Dna- mutant (ts-2) of the mouse cell Balb/3T3 is characterized. Studies with synchronized cells indicate that the defect is in DNA synthesis itself, rather than in progress toward its initiation. ts-2 supports polyoma DNA synthesis after infection at 33degreesC but not at 38degreesC. Viral DNA synthesis begun at 33degreesC is inhibited upon shift to 38degreesC. A procedure is proposed by which viral DNA synthesis can be used to distinguish different classes of cell Dna- mutants.", "contents": "Temperature-sensitive mutants of Balb/3T3 cells: description of a mutant affected in cellular and polyoma virus DNA synthesis. A temperature-sensitive Dna- mutant (ts-2) of the mouse cell Balb/3T3 is characterized. Studies with synchronized cells indicate that the defect is in DNA synthesis itself, rather than in progress toward its initiation. ts-2 supports polyoma DNA synthesis after infection at 33degreesC but not at 38degreesC. Viral DNA synthesis begun at 33degreesC is inhibited upon shift to 38degreesC. A procedure is proposed by which viral DNA synthesis can be used to distinguish different classes of cell Dna- mutants."} {"id": "PMID:182374", "title": "A quantitative study of ultramicroinjection of macromolecules into animal cells.", "content": "Improvements in the technique of ultramicroinjection of macromolecules into animal cells are described. The method is based on the Sendai virus-induced fusion of animal cells with erythrocyte ghosts containing trapped macromolecules. Fusion of hepatoma tissue culture (HTC) cells with ghosts prepared by hemolysis of erythrocytes in the presence of cytochrome C is much more efficient than fusion with ghosts prepared in the presence of bovine serum albumin (BSA) as in previous investigations. La+++ is more fficient in promoting fusion and less toxic to cells than Mn++, which was used previously. Thus in all subsequent experiments, erythrocytes were hemolyzed in the presence of cytochrome C plus other macromolecules to be trapped, and the resultant ghosts fused in the presence of La+++. The percentage of HTC cells which fused with ghosts reached 80% in many experiments. Ghosts containing 125I-BSA were used to measure the number of BSA molecules injected into HTC cells. About 10(6) BSA molecules were injected per fused cell. The overall efficiency of injection was low (about 0.02% of the starting material).", "contents": "A quantitative study of ultramicroinjection of macromolecules into animal cells. Improvements in the technique of ultramicroinjection of macromolecules into animal cells are described. The method is based on the Sendai virus-induced fusion of animal cells with erythrocyte ghosts containing trapped macromolecules. Fusion of hepatoma tissue culture (HTC) cells with ghosts prepared by hemolysis of erythrocytes in the presence of cytochrome C is much more efficient than fusion with ghosts prepared in the presence of bovine serum albumin (BSA) as in previous investigations. La+++ is more fficient in promoting fusion and less toxic to cells than Mn++, which was used previously. Thus in all subsequent experiments, erythrocytes were hemolyzed in the presence of cytochrome C plus other macromolecules to be trapped, and the resultant ghosts fused in the presence of La+++. The percentage of HTC cells which fused with ghosts reached 80% in many experiments. Ghosts containing 125I-BSA were used to measure the number of BSA molecules injected into HTC cells. About 10(6) BSA molecules were injected per fused cell. The overall efficiency of injection was low (about 0.02% of the starting material)."} {"id": "PMID:182375", "title": "Preferential synthesis of viral late RNA by nuclei isolated from SV40 lytically infected cells.", "content": "Nuclei from SV40-infected monkey cells were isolated late in lytic infection and their cell-free transcriptional activity was characterized. 3H-RNA synthesized in vitro was hybridized to excess quantities of separated SV40 DNA strands which were each covalently bound to Sepharose. It was found that 3-5% of the newly synthesized RNA is virus-specific and that the plus-strand DNA, coding for late RNA sequences, is transcribed at a rate about 15 times higher than that of the minus-strand DNA, which codes for early RNA sequences. This indicates that transcriptional control has a major role in determining the relative abundancy of early and late RNA classes in lytically infected cells.", "contents": "Preferential synthesis of viral late RNA by nuclei isolated from SV40 lytically infected cells. Nuclei from SV40-infected monkey cells were isolated late in lytic infection and their cell-free transcriptional activity was characterized. 3H-RNA synthesized in vitro was hybridized to excess quantities of separated SV40 DNA strands which were each covalently bound to Sepharose. It was found that 3-5% of the newly synthesized RNA is virus-specific and that the plus-strand DNA, coding for late RNA sequences, is transcribed at a rate about 15 times higher than that of the minus-strand DNA, which codes for early RNA sequences. This indicates that transcriptional control has a major role in determining the relative abundancy of early and late RNA classes in lytically infected cells."} {"id": "PMID:182376", "title": "Mapping of poly(A) sequences in the electron microscope reveals unusual structure of type C oncornavirus RNA molecules.", "content": "We have synthesized a convenient electron microscope label for mapping poly(A) sequences. Short lengths of poly(dT) are polymerized onto nicked circular SV40 DNA with the enzyme terminal deoxynucleotidyl transferase. An RNA or DNA molecule of interest is treated with glyoxal, hybridized briefly with the poly(dT) circles, and spread for microscopy; poly(A) stretches are clearly marked because they are attached to the poly(dT) on the easily recognized SV40 duplex circles. The RNAs of several type C oncornaviruses were examined by this method. The endogenous feline virus(RD-114), the endogenous baboon virus (BKD), and the woolly monkey sarcoma virus (WoMV) all contain a dimer of RNA subunits held together in a central secondary structure feature we call the dimer linkage structure. Both ends distal to the dimer linkage structure hybridize to the SV40-poly(dT). Assuming both poly(A)s are on the 3' ends of the subunits and that both subunits are identical, the two identical subunits are held together by interactions between sequences close to the 5' ends.", "contents": "Mapping of poly(A) sequences in the electron microscope reveals unusual structure of type C oncornavirus RNA molecules. We have synthesized a convenient electron microscope label for mapping poly(A) sequences. Short lengths of poly(dT) are polymerized onto nicked circular SV40 DNA with the enzyme terminal deoxynucleotidyl transferase. An RNA or DNA molecule of interest is treated with glyoxal, hybridized briefly with the poly(dT) circles, and spread for microscopy; poly(A) stretches are clearly marked because they are attached to the poly(dT) on the easily recognized SV40 duplex circles. The RNAs of several type C oncornaviruses were examined by this method. The endogenous feline virus(RD-114), the endogenous baboon virus (BKD), and the woolly monkey sarcoma virus (WoMV) all contain a dimer of RNA subunits held together in a central secondary structure feature we call the dimer linkage structure. Both ends distal to the dimer linkage structure hybridize to the SV40-poly(dT). Assuming both poly(A)s are on the 3' ends of the subunits and that both subunits are identical, the two identical subunits are held together by interactions between sequences close to the 5' ends."} {"id": "PMID:182377", "title": "RD-114, baboon, and woolly monkey viral RNA's compared in size and structure.", "content": "The molecular weights, subunit compositions, and secondary structure patterns of the RNAs from an endogenous baboon virus and from a woolly monkey sarcoma virus were examined and compared to the properties of the RNA of RD-114, an endogenous feline virus. The high molecular weight RNA extracted from each of these three viruses has a sedimentation coefficient of 52S, and a molecular length, measured by electron microscopy, of 16-20 kb (kb=kilobase, 1000 nucleotides). Each such RNA is a dimer, containing two monomer subunits of 8-10 kb in length (molecular weight 3 X 10(6) daltons). The two monomer subunits are joined at their non-poly(A) ends in a structure called the dimer linkage structure. The appearance of this structure is somewhat different for the different viruses. The dimer linkage dissociates at temperature estimated to be 87 degrees C in aqueous 0.1M Na+ for RD-114 and baboon viral RNAs, but at the lower temperature of 66 degrees C for woolly monkey RNA. All three viral RNAs have two large loops of similar size and position symmetrically placed on either side of the dimer linkage structure. Since the baboon virus is partially related to RD-114, and the woolly monkey virus is unrelated to either of the other two, the dimer linkage and symmetrical loops are surprisingly similar and may well be common features of type C virus RNAs.", "contents": "RD-114, baboon, and woolly monkey viral RNA's compared in size and structure. The molecular weights, subunit compositions, and secondary structure patterns of the RNAs from an endogenous baboon virus and from a woolly monkey sarcoma virus were examined and compared to the properties of the RNA of RD-114, an endogenous feline virus. The high molecular weight RNA extracted from each of these three viruses has a sedimentation coefficient of 52S, and a molecular length, measured by electron microscopy, of 16-20 kb (kb=kilobase, 1000 nucleotides). Each such RNA is a dimer, containing two monomer subunits of 8-10 kb in length (molecular weight 3 X 10(6) daltons). The two monomer subunits are joined at their non-poly(A) ends in a structure called the dimer linkage structure. The appearance of this structure is somewhat different for the different viruses. The dimer linkage dissociates at temperature estimated to be 87 degrees C in aqueous 0.1M Na+ for RD-114 and baboon viral RNAs, but at the lower temperature of 66 degrees C for woolly monkey RNA. All three viral RNAs have two large loops of similar size and position symmetrically placed on either side of the dimer linkage structure. Since the baboon virus is partially related to RD-114, and the woolly monkey virus is unrelated to either of the other two, the dimer linkage and symmetrical loops are surprisingly similar and may well be common features of type C virus RNAs."} {"id": "PMID:182379", "title": "Cloned mouse mammary cell lines requiring androgens for growth in culture.", "content": "Clonally derived cell lines have been established from the mouse mammary tumor Shionogi carcinoma 115. Physiological concentrations of androgens markedly increase the growth rate and saturation density of these clones. The cells fail to grow in 1% fetal bovine serum-supplemented medium, but addition of 10-50 nM androstanolone or testosterone results in resumption of exponential growth. Some other androgens, but not estrogens or progesterone, stimulate growth of these cells. Steroid receptors can be isolated from the cells. In addition to their effect on growth, androgens also cause a marked alteration in the cell and colony morphology of the clones.", "contents": "Cloned mouse mammary cell lines requiring androgens for growth in culture. Clonally derived cell lines have been established from the mouse mammary tumor Shionogi carcinoma 115. Physiological concentrations of androgens markedly increase the growth rate and saturation density of these clones. The cells fail to grow in 1% fetal bovine serum-supplemented medium, but addition of 10-50 nM androstanolone or testosterone results in resumption of exponential growth. Some other androgens, but not estrogens or progesterone, stimulate growth of these cells. Steroid receptors can be isolated from the cells. In addition to their effect on growth, androgens also cause a marked alteration in the cell and colony morphology of the clones."} {"id": "PMID:182380", "title": "High frequency variation in mammary tumor virus expression in cell culture.", "content": "Clonal derivatives of C3HMT murine mammary cell lines in culture demonstrate conversion of mammary tumor virus (MMTV) expression at a rate of appriximately 6 per 100 clones. This alteration is largely unidirectional from a relatively high level (MMTV(H)) to a 10 fold lower level (MMTV(L)). This high rate of MMTV(L) variant conversion is in apparent contrast to the presumably mutational rate (approximately 3 per million cells) that governs development of resistance to 6-thioguanine (TG) in the same mammary cells. In somatic cell hybrids between different MMTV TGr clones and mouse or hamster TK- cells, expression of constitutive levels of MMTV and responsiveness to dexamethasone induction is dominant. Thus MMTV expression is regulated by at least two levels of positive control, constitutive expression and glucocorticoid stimulation, but the former is subject to a high rate of variant formation.", "contents": "High frequency variation in mammary tumor virus expression in cell culture. Clonal derivatives of C3HMT murine mammary cell lines in culture demonstrate conversion of mammary tumor virus (MMTV) expression at a rate of appriximately 6 per 100 clones. This alteration is largely unidirectional from a relatively high level (MMTV(H)) to a 10 fold lower level (MMTV(L)). This high rate of MMTV(L) variant conversion is in apparent contrast to the presumably mutational rate (approximately 3 per million cells) that governs development of resistance to 6-thioguanine (TG) in the same mammary cells. In somatic cell hybrids between different MMTV TGr clones and mouse or hamster TK- cells, expression of constitutive levels of MMTV and responsiveness to dexamethasone induction is dominant. Thus MMTV expression is regulated by at least two levels of positive control, constitutive expression and glucocorticoid stimulation, but the former is subject to a high rate of variant formation."} {"id": "PMID:182381", "title": "The chick chorioallantoic membrane as a model system for the study of tissue invasion by viral transformed cells.", "content": "The chick chorioallantoic membrane (CAM) was used as an assay system to investigate the the invasive properties of viral transformed NIH/3Y3 cells. Scanning electron microscopy demonstrated that single Kirsten sarcoma virus (KiSV)-transformed cells passed between the epithelial cells of the CAM ectoderm within 6 hr of application, while viable NIH/3T3 cells did not penetrate the ectoderm within 24 hr. The transformed cells entered the mesoderm of the CAM and formed tumors of proliferating cells. The application of 5 X 10(5) KiSV-transformed cells resulted in the formation of donor cells resulted in the formation of the donor cell tumors within 5 days in 43% of the membranes. No tumors were formed when as many as 5 X 10(6) NIH/3T3 cells were applied to the membrane. NIH/3T3 cells transformed by the Abelson leukemia virus or the Moloney sarcoma virus also ivaded the CAM and formed tumors of proliferating cells within the mesoderm, while cells infected with the Moloney leukemia virus did not. NIH/3T3 cells inoculated onto the CAM 8 days after infection and transformation with KiSV formed tumors with a frequency similar to that of KiSV transformed cells that have been passaged in culture for many generations. Cells that formed invasive tumors within the mesoderm also attracted loops of host blood vessels.", "contents": "The chick chorioallantoic membrane as a model system for the study of tissue invasion by viral transformed cells. The chick chorioallantoic membrane (CAM) was used as an assay system to investigate the the invasive properties of viral transformed NIH/3Y3 cells. Scanning electron microscopy demonstrated that single Kirsten sarcoma virus (KiSV)-transformed cells passed between the epithelial cells of the CAM ectoderm within 6 hr of application, while viable NIH/3T3 cells did not penetrate the ectoderm within 24 hr. The transformed cells entered the mesoderm of the CAM and formed tumors of proliferating cells. The application of 5 X 10(5) KiSV-transformed cells resulted in the formation of donor cells resulted in the formation of the donor cell tumors within 5 days in 43% of the membranes. No tumors were formed when as many as 5 X 10(6) NIH/3T3 cells were applied to the membrane. NIH/3T3 cells transformed by the Abelson leukemia virus or the Moloney sarcoma virus also ivaded the CAM and formed tumors of proliferating cells within the mesoderm, while cells infected with the Moloney leukemia virus did not. NIH/3T3 cells inoculated onto the CAM 8 days after infection and transformation with KiSV formed tumors with a frequency similar to that of KiSV transformed cells that have been passaged in culture for many generations. Cells that formed invasive tumors within the mesoderm also attracted loops of host blood vessels."} {"id": "PMID:182382", "title": "The selection of virus-resistant Chinese hamster ovary cells.", "content": "We have selected Chinese hamster ovary (CHO) cells resistant to infection by encephalomycarditis (EMC) virus. Thus far, we have obtained five lines resistant to EMC, all of which manifest different phenotypes. Three of the five are not persistently infected with virus, while two lines produce infectious virus and grow in its presence. The nonpersistently infected lines exhibit different resistance profiles to the other viruses we have tested, and they are stable in nonselective growth conditions. Their resistance appears to be due to a genetic alteration in the cell.", "contents": "The selection of virus-resistant Chinese hamster ovary cells. We have selected Chinese hamster ovary (CHO) cells resistant to infection by encephalomycarditis (EMC) virus. Thus far, we have obtained five lines resistant to EMC, all of which manifest different phenotypes. Three of the five are not persistently infected with virus, while two lines produce infectious virus and grow in its presence. The nonpersistently infected lines exhibit different resistance profiles to the other viruses we have tested, and they are stable in nonselective growth conditions. Their resistance appears to be due to a genetic alteration in the cell."} {"id": "PMID:182383", "title": "Identification of regions of the SV40 genome which contain preferred SV40 T antigen-binding sites.", "content": "SV40 T antigen binds to SV40 DNA. Using a series of purified SV40 DNA restriction fragments, we have obtained evidence indicating that the antigen preferentially binds to three specific regions. These binding regions are contained within Endo R-Hin d(II + III) A, B, and C.", "contents": "Identification of regions of the SV40 genome which contain preferred SV40 T antigen-binding sites. SV40 T antigen binds to SV40 DNA. Using a series of purified SV40 DNA restriction fragments, we have obtained evidence indicating that the antigen preferentially binds to three specific regions. These binding regions are contained within Endo R-Hin d(II + III) A, B, and C."} {"id": "PMID:182384", "title": "Isolation and characterization of Sendai virus DI-RNAs.", "content": "When passaged at high multiplicity, four strains of Sendai virus all showed evidence that they contained defective interfering (DI) particles. RNA isolated from nucleocapsids of cells infected with the high multiplicity passage stocks was found to consist of only minor amounts of nondefective genome length RNA and major amounts of smaller RNAs, the DI-RNAs. These DI-RNAs were found to have unusual and variable sedimentation properties in sucrose gradients, but were found to represent unique segments of the viral genome by length measurements in the electron microscope and by hybridization. A striking feature of the DI-RNAs is their ability to form circular structures, indicating that the ends of the DI-RNA are complementary. The implications of this finding in terms of the mechanism of genome replication is discussed.", "contents": "Isolation and characterization of Sendai virus DI-RNAs. When passaged at high multiplicity, four strains of Sendai virus all showed evidence that they contained defective interfering (DI) particles. RNA isolated from nucleocapsids of cells infected with the high multiplicity passage stocks was found to consist of only minor amounts of nondefective genome length RNA and major amounts of smaller RNAs, the DI-RNAs. These DI-RNAs were found to have unusual and variable sedimentation properties in sucrose gradients, but were found to represent unique segments of the viral genome by length measurements in the electron microscope and by hybridization. A striking feature of the DI-RNAs is their ability to form circular structures, indicating that the ends of the DI-RNA are complementary. The implications of this finding in terms of the mechanism of genome replication is discussed."} {"id": "PMID:182385", "title": "A significant lag in the induction of ovalbumin messenger RNA by steroid hormones: a receptor translocation hypothesis.", "content": "Although ovalbumin and conalbumin mRNA accumulate in the same tubular gland cells of the chick oviduct in response to estrogen or progesterone treatment, the kinetics of induction are markedly different. Conalbumin mRNA begins to accumulate within 30 min after estrogen administration, whereas there is a lag of approximately 3 hr before ovalbumin mRNA begins to accumulate, as measured by three independent assays. The kinetics of estrogen-receptor binding to chromatin indicate that these sites are saturated within 15 min of estrogen administration to the chicks, demonstrating that the lag is not due to slow uptake of the steroid. Suboptimal doses of estrogen produce the same lag, but the resultant rate of ovalbumin mRNA accumulation is lower than with an optimal dose. Partial induction of ovalbumin mRNA by a low dose of estrogen does not shorten the lag with an optimal dose. With progesteone, there is a lag of about 2 hr before either ovalbumin or conalbumin mRNA begins to accumulate. Treatment of chicks with hydroxyurea shortens the lag for ovalbumin induction with either hormone. Inhibition of protein synthesis with emetine does not prevent the accumulation of either ovalbumin or conalbumin mRNA. With cycloheximide, however, ovalbumin mRNA accumulation can be prevented. The existence of a lag suggests that there are intermediate steps between the binding of steroid receptors to chromatin and the induction of ovalbumin mRNA. There are basically two models to explain these delays in response: one involving the accumulation of an essential intermediate, and the other involving a rate-limiting translocation of steroid receptors from initial nonproductive chromatin-binding sites to productive sites. Several aspects of the kinetics of ovalbumin mRNA induction are more consistent with the latter model.", "contents": "A significant lag in the induction of ovalbumin messenger RNA by steroid hormones: a receptor translocation hypothesis. Although ovalbumin and conalbumin mRNA accumulate in the same tubular gland cells of the chick oviduct in response to estrogen or progesterone treatment, the kinetics of induction are markedly different. Conalbumin mRNA begins to accumulate within 30 min after estrogen administration, whereas there is a lag of approximately 3 hr before ovalbumin mRNA begins to accumulate, as measured by three independent assays. The kinetics of estrogen-receptor binding to chromatin indicate that these sites are saturated within 15 min of estrogen administration to the chicks, demonstrating that the lag is not due to slow uptake of the steroid. Suboptimal doses of estrogen produce the same lag, but the resultant rate of ovalbumin mRNA accumulation is lower than with an optimal dose. Partial induction of ovalbumin mRNA by a low dose of estrogen does not shorten the lag with an optimal dose. With progesteone, there is a lag of about 2 hr before either ovalbumin or conalbumin mRNA begins to accumulate. Treatment of chicks with hydroxyurea shortens the lag for ovalbumin induction with either hormone. Inhibition of protein synthesis with emetine does not prevent the accumulation of either ovalbumin or conalbumin mRNA. With cycloheximide, however, ovalbumin mRNA accumulation can be prevented. The existence of a lag suggests that there are intermediate steps between the binding of steroid receptors to chromatin and the induction of ovalbumin mRNA. There are basically two models to explain these delays in response: one involving the accumulation of an essential intermediate, and the other involving a rate-limiting translocation of steroid receptors from initial nonproductive chromatin-binding sites to productive sites. Several aspects of the kinetics of ovalbumin mRNA induction are more consistent with the latter model."} {"id": "PMID:182388", "title": "[Histiocytic medullary reticulosis and herpetic necrotizing inclusion hepatitis].", "content": "A male aged 47 suffered from the syndrome of histiocytic medullary reticulosis terminating lethally within one year. Because of the finding of a necrotizing inclusion hepatitis of the herpetic type at autopsy, intranuclear inclusions were retrospectively searched for in the tumour tissue. Inclusions were found, on the one hand, in a bioptic sample obained from a lymph node at the beginning of the disease and, on the other hand, in lympatic tissue and bone marrow obtained at autopsy. The relation of histiocytic medullary reticulosis to the herpetic infection has been discussed.", "contents": "[Histiocytic medullary reticulosis and herpetic necrotizing inclusion hepatitis]. A male aged 47 suffered from the syndrome of histiocytic medullary reticulosis terminating lethally within one year. Because of the finding of a necrotizing inclusion hepatitis of the herpetic type at autopsy, intranuclear inclusions were retrospectively searched for in the tumour tissue. Inclusions were found, on the one hand, in a bioptic sample obained from a lymph node at the beginning of the disease and, on the other hand, in lympatic tissue and bone marrow obtained at autopsy. The relation of histiocytic medullary reticulosis to the herpetic infection has been discussed."} {"id": "PMID:182389", "title": "[Malignant nesidioma with 2 types of secretory granules in tumor cells].", "content": "A case has been described of a male aged 38 with a malignant nesidioma. The clinical examination disclosed marked hepatomegaly, variable hypertension associated with cool sweating, agitation and transient hyperglycaemia. The primary tumour as well as the metastases in the liver weighing over 13 kg were histologically of trabecular structure and stained positively with the methods of Bodian and grimelius. The impregnation for D-cells according to Rohoznick\u00e1 and Vortel was positive in isolated cells only. Ultrastructurally, the tumor cells could be divided in two types. The more numerous Type I cells contained rather small secretory granules morphologically resembling A granules of islet cells, and staining positively with impregnation methods for A-cells on the ultrastructural level. Type II cells contained, in addition to the formerly described ones, another type of granules appearing as large, slightly osmiophilic ones characteristic of the D-cells of Langerhan's islets and positive with the impregnation methods for D-cells. The type II tumour cells must be therefore regarded as a mixed cell type containing two types of secretory granules.", "contents": "[Malignant nesidioma with 2 types of secretory granules in tumor cells]. A case has been described of a male aged 38 with a malignant nesidioma. The clinical examination disclosed marked hepatomegaly, variable hypertension associated with cool sweating, agitation and transient hyperglycaemia. The primary tumour as well as the metastases in the liver weighing over 13 kg were histologically of trabecular structure and stained positively with the methods of Bodian and grimelius. The impregnation for D-cells according to Rohoznick\u00e1 and Vortel was positive in isolated cells only. Ultrastructurally, the tumor cells could be divided in two types. The more numerous Type I cells contained rather small secretory granules morphologically resembling A granules of islet cells, and staining positively with impregnation methods for A-cells on the ultrastructural level. Type II cells contained, in addition to the formerly described ones, another type of granules appearing as large, slightly osmiophilic ones characteristic of the D-cells of Langerhan's islets and positive with the impregnation methods for D-cells. The type II tumour cells must be therefore regarded as a mixed cell type containing two types of secretory granules."} {"id": "PMID:182390", "title": "On the reaction kinetics in water of 1,3-propane sultone and 1,4-butane sultone: a comparison of reaction rates and mutagenic activities of some alkylating agents.", "content": "To determine correlations between the biological action pattern and chemical reactivity of alkylating agents, the rate constants for reactions of 1,3-propane sultone and 1,4-butane sultone with a series of nucleophiles at 37 degrees C have been determined. Previously published data on the mutagenicity of the two sultones and of some alkyl methanesulfonates and dialkyl sulfates towards Schizosaccharomyces pombe have been used in the evaluation of the dependence of mutagenic effectiveness on chemical reactivity. It is of interest to note that the mutagenic effectiveness of the two sultones, if expressed per alkylating event at a certain low nucleophilicity is the same as that of e.g. methyl methanesulfonate and ethyl methanesulfonate.", "contents": "On the reaction kinetics in water of 1,3-propane sultone and 1,4-butane sultone: a comparison of reaction rates and mutagenic activities of some alkylating agents. To determine correlations between the biological action pattern and chemical reactivity of alkylating agents, the rate constants for reactions of 1,3-propane sultone and 1,4-butane sultone with a series of nucleophiles at 37 degrees C have been determined. Previously published data on the mutagenicity of the two sultones and of some alkyl methanesulfonates and dialkyl sulfates towards Schizosaccharomyces pombe have been used in the evaluation of the dependence of mutagenic effectiveness on chemical reactivity. It is of interest to note that the mutagenic effectiveness of the two sultones, if expressed per alkylating event at a certain low nucleophilicity is the same as that of e.g. methyl methanesulfonate and ethyl methanesulfonate."} {"id": "PMID:182391", "title": "The sensitivity of HeLa and Chinese hamster (ovary) cells to methylene dimethane sulphonate.", "content": "HeLa and Chinese hamster (ovary) cells were exposed in vitro to methylene dimethanesulphonate (MDMS) and their survival of colony-forming ability was assayed in monolayer culture. Asynchronous cultures were exposed to the drug for the whole culture period but cell survival was complicated by the toxicity of formaldehyde which is a final breakdown product of the drug. A short treatment schedule of 15 min within the hydrolytic half life of the agent was therefore employed and the response of synchronous cultures of HeLa cells was then assayed throughout the course of the cells cycle. Cells were most sensitive at the beginning of the DNA synthetic phase (early-S) and most resistant at the end (late-S).", "contents": "The sensitivity of HeLa and Chinese hamster (ovary) cells to methylene dimethane sulphonate. HeLa and Chinese hamster (ovary) cells were exposed in vitro to methylene dimethanesulphonate (MDMS) and their survival of colony-forming ability was assayed in monolayer culture. Asynchronous cultures were exposed to the drug for the whole culture period but cell survival was complicated by the toxicity of formaldehyde which is a final breakdown product of the drug. A short treatment schedule of 15 min within the hydrolytic half life of the agent was therefore employed and the response of synchronous cultures of HeLa cells was then assayed throughout the course of the cells cycle. Cells were most sensitive at the beginning of the DNA synthetic phase (early-S) and most resistant at the end (late-S)."} {"id": "PMID:182392", "title": "Mechanism of the inhibition of transcription by PR toxin, a mycotoxin from Penicillium roqueforti.", "content": "PR toxin, a mycotoxin synthesized by Penicillium roqueforti, impairs the transcriptional process in liver cells; the two main RNA polymerase systems (enzymes A and B) are affected by PR toxin. The toxin does not require an enzymic conversion before interfering with in vitro RNA synthesis. Addition of ammonium sulphate completely prevents the inhibition of transcription by PR toxin. In vitro results, using RNA polymerase purified from E. coli, suggest that PR toxin impairs the activity of the RNA polymerase itself. Regarding the step of the transcription process affected, it is shown that PR toxin inhibits both initiation and elongation of the polynucleotide chain.", "contents": "Mechanism of the inhibition of transcription by PR toxin, a mycotoxin from Penicillium roqueforti. PR toxin, a mycotoxin synthesized by Penicillium roqueforti, impairs the transcriptional process in liver cells; the two main RNA polymerase systems (enzymes A and B) are affected by PR toxin. The toxin does not require an enzymic conversion before interfering with in vitro RNA synthesis. Addition of ammonium sulphate completely prevents the inhibition of transcription by PR toxin. In vitro results, using RNA polymerase purified from E. coli, suggest that PR toxin impairs the activity of the RNA polymerase itself. Regarding the step of the transcription process affected, it is shown that PR toxin inhibits both initiation and elongation of the polynucleotide chain."} {"id": "PMID:182393", "title": "Binding of thiols to microsomal cytochrome P-450.", "content": "Lipophilic thiol compounds interact spectrally with liver microsomes from phenobarbital-pretreated rats by formation of unusual optical difference spectra with peaks at 378, 471, 522 and 593 nm in the oxidized state. The binding kinetics were biphasic. The EPR spectrum of cytochrome P-450 was slightly modified but the magnitude of the low-spin signal was unchanged. n-Octanethiol competitively displaced metyrapone and n-octane from the active site of cytochrome P-450. Other thiols behaved similarly with variations in the magnitude and the affinity of the binding process. Tertiary thiols caused the formation of the high-spin cytochrome P-450 substrate complex, and model studies with myoglobin revealed that steric hindrance prevented the liganding of the tertiary thiol group to the ferric cytochrome P-450. Addition of thiols to dithionite reduced microsomes resulted in relatively small spectral changes with maxima at 449 nm typical for ligand complexes of the ferrous cytochrome. It was concluded that lipophilic thiols can be bound as ligands by at least two species of oxidized cytochrome P-450 which represent, however, not more than about one fifth of the total cytochrome P-450 content in liver microsomes from phenobarbital-pretreated rats.", "contents": "Binding of thiols to microsomal cytochrome P-450. Lipophilic thiol compounds interact spectrally with liver microsomes from phenobarbital-pretreated rats by formation of unusual optical difference spectra with peaks at 378, 471, 522 and 593 nm in the oxidized state. The binding kinetics were biphasic. The EPR spectrum of cytochrome P-450 was slightly modified but the magnitude of the low-spin signal was unchanged. n-Octanethiol competitively displaced metyrapone and n-octane from the active site of cytochrome P-450. Other thiols behaved similarly with variations in the magnitude and the affinity of the binding process. Tertiary thiols caused the formation of the high-spin cytochrome P-450 substrate complex, and model studies with myoglobin revealed that steric hindrance prevented the liganding of the tertiary thiol group to the ferric cytochrome P-450. Addition of thiols to dithionite reduced microsomes resulted in relatively small spectral changes with maxima at 449 nm typical for ligand complexes of the ferrous cytochrome. It was concluded that lipophilic thiols can be bound as ligands by at least two species of oxidized cytochrome P-450 which represent, however, not more than about one fifth of the total cytochrome P-450 content in liver microsomes from phenobarbital-pretreated rats."} {"id": "PMID:182394", "title": "Copper toxicity: evidence for the conversion of cupric to cuprous copper in vivo under anaerobic conditions.", "content": "We have determined the toxicity to cells of Escherichia coli B of cupric copper applied under aerobic and anaerobic conditions in two ways. The growth of cells in liquid medium incorporating cupric copper shows differential inhibition, comparing aerobic and anaerobic conditions--toxicity being greater under anoxia. The growth of colonies upon agar plates incorporating cupric copper does not show such a differential effect. We conclude that colonies on plates are largely anoxic even when incubated aerobically. EPR spectra of cells obtained at various times after application of cupric copper under anoxic conditions indicate the conversion of a considerable proportion of the Cu(II) to a non-paramagnetic species, probably Cu(I). We demonstrate that Cu(I) is more toxic than Cu(II) to cells when applied under anoxic conditions and conclude that the difference in toxicity of Cu(II) applied to cells under aerobic and anaerobic conditions results from the greater extent of reduction of Cu(II) to Cu(I) under anaerobic conditions.", "contents": "Copper toxicity: evidence for the conversion of cupric to cuprous copper in vivo under anaerobic conditions. We have determined the toxicity to cells of Escherichia coli B of cupric copper applied under aerobic and anaerobic conditions in two ways. The growth of cells in liquid medium incorporating cupric copper shows differential inhibition, comparing aerobic and anaerobic conditions--toxicity being greater under anoxia. The growth of colonies upon agar plates incorporating cupric copper does not show such a differential effect. We conclude that colonies on plates are largely anoxic even when incubated aerobically. EPR spectra of cells obtained at various times after application of cupric copper under anoxic conditions indicate the conversion of a considerable proportion of the Cu(II) to a non-paramagnetic species, probably Cu(I). We demonstrate that Cu(I) is more toxic than Cu(II) to cells when applied under anoxic conditions and conclude that the difference in toxicity of Cu(II) applied to cells under aerobic and anaerobic conditions results from the greater extent of reduction of Cu(II) to Cu(I) under anaerobic conditions."} {"id": "PMID:182395", "title": "Arenavirus taxonomy: a review.", "content": "Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group.", "contents": "Arenavirus taxonomy: a review. Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group."} {"id": "PMID:182396", "title": "Morphology and morphogenesis of arenaviruses.", "content": "Arenaviruses have unique structural characteristics; they are pleomorphic, have a mean diameter of 110-130 nm, and consist of a membranous envelope with surface projections surrounding an interior containing ribosomes and filaments. Virus particles bud from plasma membranes of infected cells and in many cases large intracytoplasmic inclusion bodies are formed. These characteristics allow generic identification, but not differentiation of individual viruses. Ultrastructural identification of virus particles and pathological processes in infected tissues of man and experimental animals is important in understanding the nature of arenaviral pathogenesis Such identification also contributes to our understanding of the mechanisms of viral shedding and transmission in reservoir host species.", "contents": "Morphology and morphogenesis of arenaviruses. Arenaviruses have unique structural characteristics; they are pleomorphic, have a mean diameter of 110-130 nm, and consist of a membranous envelope with surface projections surrounding an interior containing ribosomes and filaments. Virus particles bud from plasma membranes of infected cells and in many cases large intracytoplasmic inclusion bodies are formed. These characteristics allow generic identification, but not differentiation of individual viruses. Ultrastructural identification of virus particles and pathological processes in infected tissues of man and experimental animals is important in understanding the nature of arenaviral pathogenesis Such identification also contributes to our understanding of the mechanisms of viral shedding and transmission in reservoir host species."} {"id": "PMID:182397", "title": "Antigenic properties of the arenaviruses.", "content": "Arenaviruses are known to show antigenic relationships in the complement-fixation (CF) and fluorescent antibody tests but not in the neutralization test. The humoral response to some of the arenaviruses is characterized by a dissociation between the antibodies determined by the CF test and those determined by the neutralization test and also by its late appearance following natural infection. Investigations are reported showing that, as regards the CF test, Junin, Machupo, Amapari, and Tacaribe viruses are closely related, while LCM and Lassa viruses are distantly related to each other and to the remaining viruses in the group. Studies by agar gel diffusion and precipitation have shown complete specificity except among viruses that are very closely related in the CF test. Observations with sera from persons infected with Lassa fever virus show that CF antibodies rarely appear before the 18th day after onset; they can persist, with diminishing titres, for up to 6 years.", "contents": "Antigenic properties of the arenaviruses. Arenaviruses are known to show antigenic relationships in the complement-fixation (CF) and fluorescent antibody tests but not in the neutralization test. The humoral response to some of the arenaviruses is characterized by a dissociation between the antibodies determined by the CF test and those determined by the neutralization test and also by its late appearance following natural infection. Investigations are reported showing that, as regards the CF test, Junin, Machupo, Amapari, and Tacaribe viruses are closely related, while LCM and Lassa viruses are distantly related to each other and to the remaining viruses in the group. Studies by agar gel diffusion and precipitation have shown complete specificity except among viruses that are very closely related in the CF test. Observations with sera from persons infected with Lassa fever virus show that CF antibodies rarely appear before the 18th day after onset; they can persist, with diminishing titres, for up to 6 years."} {"id": "PMID:182398", "title": "Antigenic relationships of lymphocytic choriomeningitis virus and Tacaribe virus in the indirect haemagglutination test.", "content": "The indirect haemagglutination test has been developed for use with LCM and Tacaribe viruses employing antibody-sensitized erythrocytes. Both in this test and in the indirect haemagglutination inhibition test cross-reactions between LCM and Tacaribe viruses were revealed. This opens new perspectives for group and species identification of arenaviruses.", "contents": "Antigenic relationships of lymphocytic choriomeningitis virus and Tacaribe virus in the indirect haemagglutination test. The indirect haemagglutination test has been developed for use with LCM and Tacaribe viruses employing antibody-sensitized erythrocytes. Both in this test and in the indirect haemagglutination inhibition test cross-reactions between LCM and Tacaribe viruses were revealed. This opens new perspectives for group and species identification of arenaviruses."} {"id": "PMID:182399", "title": "Infection of wild and laboratory animals with Machupo and Latino viruses.", "content": "Natural infection with Machupo and Latino viruses occurs only in the cricetine rodent Calomys callosus. Machupo virus induces fatal infection in suckling mice and hamsters, and in adult guinea-pigs, marmosets, and rhesus monkeys. Latino virus kills only suckling hamsters; it produces chronic but non-viraemic infection in Calomys rodents.Machupo virus, in contrast, induces a viraemic immunotolerant infection in suckling Calomys, and a split response in animals more than 9 days of age. Tolerant infection is associated with haemolytic anaemia and splenomegaly, lesions not observed in animals able to clear viraemia and produce circulating neutralizing antibodies. Experimental increase in the fraction of tolerant response was obtained by decreasing the virus dose or by phenotypic inbreeding of rodents. Long-term effects of tolerant infection included mild runting, decreased survival time, and almost total sterility among females, largely caused by fatal virus infection of embryos.", "contents": "Infection of wild and laboratory animals with Machupo and Latino viruses. Natural infection with Machupo and Latino viruses occurs only in the cricetine rodent Calomys callosus. Machupo virus induces fatal infection in suckling mice and hamsters, and in adult guinea-pigs, marmosets, and rhesus monkeys. Latino virus kills only suckling hamsters; it produces chronic but non-viraemic infection in Calomys rodents.Machupo virus, in contrast, induces a viraemic immunotolerant infection in suckling Calomys, and a split response in animals more than 9 days of age. Tolerant infection is associated with haemolytic anaemia and splenomegaly, lesions not observed in animals able to clear viraemia and produce circulating neutralizing antibodies. Experimental increase in the fraction of tolerant response was obtained by decreasing the virus dose or by phenotypic inbreeding of rodents. Long-term effects of tolerant infection included mild runting, decreased survival time, and almost total sterility among females, largely caused by fatal virus infection of embryos."} {"id": "PMID:182400", "title": "Tamiami virus infection in mice and cotton rats.", "content": "Tamiami virus produces a lethal encephalitis in suckling mice, and the illness is mediated, at least in part, by cellular immunity. Infection of extraneural organs, including lymphoid organs, is limited. The same virus produces a widespread infection in its natural host, the cotton rat, but neither symptomatic illness nor cytopathology results. Since antibody is produced, as in the murine infection, suppression of cellular immunity to the virus may be responsible for the non-cytolytic infection. Lymphoid tissue is extensively infected in the cotton rat and a relationship between this lymphotropism and immunosuppression is suggested.", "contents": "Tamiami virus infection in mice and cotton rats. Tamiami virus produces a lethal encephalitis in suckling mice, and the illness is mediated, at least in part, by cellular immunity. Infection of extraneural organs, including lymphoid organs, is limited. The same virus produces a widespread infection in its natural host, the cotton rat, but neither symptomatic illness nor cytopathology results. Since antibody is produced, as in the murine infection, suppression of cellular immunity to the virus may be responsible for the non-cytolytic infection. Lymphoid tissue is extensively infected in the cotton rat and a relationship between this lymphotropism and immunosuppression is suggested."} {"id": "PMID:182401", "title": "Experimental biology and pathogenesis of Junin virus infection in animals and man.", "content": "A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl(3)) strains. Guinea-pigs inoculated with the XJ Cl(3) strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus.", "contents": "Experimental biology and pathogenesis of Junin virus infection in animals and man. A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl(3)) strains. Guinea-pigs inoculated with the XJ Cl(3) strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus."} {"id": "PMID:182402", "title": "Pathogenesis of Machupo virus infection in primates.", "content": "Experimental Machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. Cumulative mortality during the two phases was 80% and 95% respectively. Attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys.", "contents": "Pathogenesis of Machupo virus infection in primates. Experimental Machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. Cumulative mortality during the two phases was 80% and 95% respectively. Attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys."} {"id": "PMID:182403", "title": "The structure of rodent faunas associated with arenaviral infections.", "content": "The biogeographical examination of rodent faunas associated with arenaviruses reveals two distinct patterns. Lymphocytic choriomeningitis (LCM) virus is associated primarily with a single murid species, Mus musculus, although it is also known to cause laboratory infections in other species. On the other hand, the arenaviruses from the Western hemisphere are associated exclusively with a large and diverse group of cricetid rodents. Studies to date, although limited, have not demonstrated their association with any other rodent groups, although in South America alone at least twelve other rodent families are known. Evidence at the present time indicates that Lassa virus is only associated with a common African rodent, Mastomys natalensis. From this limited evidence it is as yet difficult to determine whether Lassa virus will follow the pattern of the South American arenaviruses, most of which are known from several species of rodents, or that of LCM virus, which appears to be associated with only a single rodent species. In this paper, the history and structure of South American, Eurasian, and African rodent faunas are described.", "contents": "The structure of rodent faunas associated with arenaviral infections. The biogeographical examination of rodent faunas associated with arenaviruses reveals two distinct patterns. Lymphocytic choriomeningitis (LCM) virus is associated primarily with a single murid species, Mus musculus, although it is also known to cause laboratory infections in other species. On the other hand, the arenaviruses from the Western hemisphere are associated exclusively with a large and diverse group of cricetid rodents. Studies to date, although limited, have not demonstrated their association with any other rodent groups, although in South America alone at least twelve other rodent families are known. Evidence at the present time indicates that Lassa virus is only associated with a common African rodent, Mastomys natalensis. From this limited evidence it is as yet difficult to determine whether Lassa virus will follow the pattern of the South American arenaviruses, most of which are known from several species of rodents, or that of LCM virus, which appears to be associated with only a single rodent species. In this paper, the history and structure of South American, Eurasian, and African rodent faunas are described."} {"id": "PMID:182405", "title": "Rodent control programmes in areas affected by Bolivian haemorrhagic fever.", "content": "Bolivian haemorrhagic fever (BHF) caused by Machupo virus is acquired by contact with the excretions and secretions of Calomys callosus, an indigenous cricetine rodent which is preadapted to peridomestic habitats. It competes successfully with Mus musculus, but not with Rattus rattus. A successful disease control programme has functioned in Beni Department since 1964. It is based on trapping surveys and the detection of splenomegaly in Calomys rodents as an index of chronic virus infection. Mass trapping and poisoning are used initially, and regular trapping is employed to control Calomys populations in towns where disease has occurred. More than 1000 cases of BHF were recorded from 1960-1964, but less than 200 in the past 10 years. The cost of this programme is approximately $30 000 annually.", "contents": "Rodent control programmes in areas affected by Bolivian haemorrhagic fever. Bolivian haemorrhagic fever (BHF) caused by Machupo virus is acquired by contact with the excretions and secretions of Calomys callosus, an indigenous cricetine rodent which is preadapted to peridomestic habitats. It competes successfully with Mus musculus, but not with Rattus rattus. A successful disease control programme has functioned in Beni Department since 1964. It is based on trapping surveys and the detection of splenomegaly in Calomys rodents as an index of chronic virus infection. Mass trapping and poisoning are used initially, and regular trapping is employed to control Calomys populations in towns where disease has occurred. More than 1000 cases of BHF were recorded from 1960-1964, but less than 200 in the past 10 years. The cost of this programme is approximately $30 000 annually."} {"id": "PMID:182406", "title": "Protection of monkeys against Machupo virus by the passive administration of Bolivian haemorrhagic fever immunoglobulin (human origin).", "content": "Bolivian haemorrhagic fever immunoglobulin of human origin, given either prior to or shortly after experimental infection with Machupo virus, protected rhesus and cynomolgus monkeys against initial clinical illness. Some survivors developed severe neurological signs 30-47 days after virus inoculation and died 4-6 days later. Results from one of the experiments suggested that the development of neurological signs was associated more frequently with high doses of immunoglobulin than with intermediate or low doses.", "contents": "Protection of monkeys against Machupo virus by the passive administration of Bolivian haemorrhagic fever immunoglobulin (human origin). Bolivian haemorrhagic fever immunoglobulin of human origin, given either prior to or shortly after experimental infection with Machupo virus, protected rhesus and cynomolgus monkeys against initial clinical illness. Some survivors developed severe neurological signs 30-47 days after virus inoculation and died 4-6 days later. Results from one of the experiments suggested that the development of neurological signs was associated more frequently with high doses of immunoglobulin than with intermediate or low doses."} {"id": "PMID:182407", "title": "Status of arenavirus vaccines and their application.", "content": "A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain.Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man.", "contents": "Status of arenavirus vaccines and their application. A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain.Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man."} {"id": "PMID:182408", "title": "[Action of an ATP analog, adenosine 5'-hyophosphophosphate in the reactions catalysed by hexokinase and fructose-6-phosphate kinase].", "content": "Adenosine 5'-hypoposphate phosphorylates glucose and fructose 6-phosphate in the presence of hexokinase and fructose 6-phosphate kinase respectively. It behaves as a competitive inhibitor versus ATP in the hexokinase reaction. Its affinity for the two enzymes is similar to that of ATP, the maximal velocities being however much lower.", "contents": "[Action of an ATP analog, adenosine 5'-hyophosphophosphate in the reactions catalysed by hexokinase and fructose-6-phosphate kinase]. Adenosine 5'-hypoposphate phosphorylates glucose and fructose 6-phosphate in the presence of hexokinase and fructose 6-phosphate kinase respectively. It behaves as a competitive inhibitor versus ATP in the hexokinase reaction. Its affinity for the two enzymes is similar to that of ATP, the maximal velocities being however much lower."} {"id": "PMID:182409", "title": "[Possible role of cell contact in the control of a differentiation program in Dictyostelium discoideum].", "content": "Synthesis of cAMP-phosphodiesterase falls at the end of the aggregation phase in Dictyostelium discoideum. Exogenous cAMP pulses, known to induce they synthesis of that enzyme during the course of the aggregation process, do not prevent the shut off of enzyme synthesis. Specific intercellular contacts which form at the end of aggregation seem to be required for the inhibition of enzyme synthesis.", "contents": "[Possible role of cell contact in the control of a differentiation program in Dictyostelium discoideum]. Synthesis of cAMP-phosphodiesterase falls at the end of the aggregation phase in Dictyostelium discoideum. Exogenous cAMP pulses, known to induce they synthesis of that enzyme during the course of the aggregation process, do not prevent the shut off of enzyme synthesis. Specific intercellular contacts which form at the end of aggregation seem to be required for the inhibition of enzyme synthesis."} {"id": "PMID:182410", "title": "[Demonstration of nucleotide pyrophosphatase and phosphohydrolase activities in normal lymphocyte of Balb/c mice and absence of these activities in YC8 tumor cells and in lymphocytes of animals with YC8 lymphoma].", "content": "Saline extraction of tumor cells from YC8 lymphoma transplanted in Balb/c Mice, of lymphocytes from animals bearing this tumor and of lymphocytes from control animals, allowed us to show important hydrolytic activities towards UDP-[(14C)]-galactose and galactose-[(14C)]-1-phosphate in normal lymphocytes. These activities disappear in lymphocytes from Mice bearing this tumor and in tumor cells themselves.", "contents": "[Demonstration of nucleotide pyrophosphatase and phosphohydrolase activities in normal lymphocyte of Balb/c mice and absence of these activities in YC8 tumor cells and in lymphocytes of animals with YC8 lymphoma]. Saline extraction of tumor cells from YC8 lymphoma transplanted in Balb/c Mice, of lymphocytes from animals bearing this tumor and of lymphocytes from control animals, allowed us to show important hydrolytic activities towards UDP-[(14C)]-galactose and galactose-[(14C)]-1-phosphate in normal lymphocytes. These activities disappear in lymphocytes from Mice bearing this tumor and in tumor cells themselves."} {"id": "PMID:182411", "title": "[Induction of dolykaryocytes by vesicular stomatitis virus in XC rat cells].", "content": "V.S.V. induced polycaryocytes in rat embryonic fibroblasts, transformed by the Prague strain of Sarcoma Rous (XC cells). This fusion is strictly dependent on the expression of the viral genome and is probably due to the incorporation of viral antigens in the cell membrane. The integrity of cellular RNA synthesis is however not required. The fusion is probably due to a membrane structure characteristic of these transformed cells.", "contents": "[Induction of dolykaryocytes by vesicular stomatitis virus in XC rat cells]. V.S.V. induced polycaryocytes in rat embryonic fibroblasts, transformed by the Prague strain of Sarcoma Rous (XC cells). This fusion is strictly dependent on the expression of the viral genome and is probably due to the incorporation of viral antigens in the cell membrane. The integrity of cellular RNA synthesis is however not required. The fusion is probably due to a membrane structure characteristic of these transformed cells."} {"id": "PMID:182412", "title": "The role of cyclic adenosine 3', 5'-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle.", "content": "We studied the relationships between the positive inotropic effects of isoproterenol, increased frequency of contraction or paired electrical stimulation, and cyclic AMP concentration and phosphorylase activity in isolated guinea pig papillary muscles. The minimum concentration of isoproterenol (10 nM) that augmented isometric force development increased cyclic AMP concentration. However 100 nM isoproterenol was required to increase the phosphorylase activity ratio (-AMP/+AMP) from 0.15 +/- 0.03 to 0.25 +/- 0.03. After addition of 1 muM isoproterenol to the bath, cyclic AMP increased within 0.5 minute from 0.58 +/- 0.03 to 1.04 +/- 0.13 mol/kg (wet weight), peak contractile force was elevated 2-fold at 1 minute, and the phosphorylase activity ratio rose to 0.40 +/- 0.02 in 4 minutes. Although an increase in contraction frequency (6/min to 36/ min) and paired stimulation produced more than a 3-fold increase in peak contractile force, there were no changes in cyclic AMP and phosphorylase activity. The cyclic AMP concentration during diastole was 0.60 +/- 0.04 and in midsystole, 0.55 +/- 0.03 mumol/kg. Anoxia increased the phosphorylase activity ratio from 0.19 +/-0.02 to 0.41 +/- 0.04 without elevation of cyclic AMP concentration. Removal of Ca2+ from the bathing medium prevented active force development and the anoxic increase in phosphorylase activity, but did not prevent the isoproterenol-induced increase in cyclic AMP and phosphorylase. These results suggest that cyclic AMP is a factor in the catecholamine-induced enhancement of inotropic state. However, it does not appear to play a role in the maintained augmentation of inotropic state produced by increased contraction frequency and paired stimulation, nor does the concentration of the cycle nucleotide appear to vary during the contraction cycle or during anoxia. Extracellular Ca2+ is required for contraction, the positive inotropic aciton of catecholamines and phosphorylase b to a conversion by anoxia.", "contents": "The role of cyclic adenosine 3', 5'-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle. We studied the relationships between the positive inotropic effects of isoproterenol, increased frequency of contraction or paired electrical stimulation, and cyclic AMP concentration and phosphorylase activity in isolated guinea pig papillary muscles. The minimum concentration of isoproterenol (10 nM) that augmented isometric force development increased cyclic AMP concentration. However 100 nM isoproterenol was required to increase the phosphorylase activity ratio (-AMP/+AMP) from 0.15 +/- 0.03 to 0.25 +/- 0.03. After addition of 1 muM isoproterenol to the bath, cyclic AMP increased within 0.5 minute from 0.58 +/- 0.03 to 1.04 +/- 0.13 mol/kg (wet weight), peak contractile force was elevated 2-fold at 1 minute, and the phosphorylase activity ratio rose to 0.40 +/- 0.02 in 4 minutes. Although an increase in contraction frequency (6/min to 36/ min) and paired stimulation produced more than a 3-fold increase in peak contractile force, there were no changes in cyclic AMP and phosphorylase activity. The cyclic AMP concentration during diastole was 0.60 +/- 0.04 and in midsystole, 0.55 +/- 0.03 mumol/kg. Anoxia increased the phosphorylase activity ratio from 0.19 +/-0.02 to 0.41 +/- 0.04 without elevation of cyclic AMP concentration. Removal of Ca2+ from the bathing medium prevented active force development and the anoxic increase in phosphorylase activity, but did not prevent the isoproterenol-induced increase in cyclic AMP and phosphorylase. These results suggest that cyclic AMP is a factor in the catecholamine-induced enhancement of inotropic state. However, it does not appear to play a role in the maintained augmentation of inotropic state produced by increased contraction frequency and paired stimulation, nor does the concentration of the cycle nucleotide appear to vary during the contraction cycle or during anoxia. Extracellular Ca2+ is required for contraction, the positive inotropic aciton of catecholamines and phosphorylase b to a conversion by anoxia."} {"id": "PMID:182413", "title": "Swine aortic smooth muscle in tissue culture. Some effects of purified swine lipoproteins on cell growth and morphology.", "content": "Smooth muscle cells (SMC) were grown from inner media explants of swine aorta and used as a model for studying the role of lipoproteins in atherogenesis. These cultured cells retain the characteristics of SMC through multiple passages. Cell growth curves, in time, were obtained by using standard counting techniques, SMC grew slowly (0.019 cycle/day) in modified Dulbecco-Vogt medium supplemented with 1.5% swine serum. Purified lipoproteins were prepared from three normolipidemic and two hyperlipidemic (cholesterol-fed) swine. When the medium of 84 growth experiments was supplemented with these lipoproteins, SMC growth rate increased linearly with lipoprotein cholesterol concentration up to 10 mg/dl. At 10 mg/dl of lipoprotein cholesterol, very low density lipoproteins (VLDL) increased growth rate 7.2-fold (P less than 0.01); low density lipoproteins (LDL) 5.7-fold (P less than 0.01); high density lipoproteins (HDL2) 3,4-fold (P less than 0.02); and HDLc, and lipoprotein appearing in the hyperlipidemic swine, 3.0-fold (P less than 0.01). Addition of 10% lipoprotein-free serum stimulated growth rate 6.0-fold (P less than 0.01). There was no difference between normo- and hyperlipidemic lipoproteins with respect to cell growth rate. Factors present in the ultracentrifugal bottom, and factors appearing during the platelet release reaction, were shown to contribute to the SMC growth response. Morphological alterations characteristic of intimal foam cells occurred in SMC grown in VLDL at triglyceride levels in excess of 15 mg per 100 ml. Thus there are distinct parallels between SMC response in this model in vitro and atherogenesis in vivo.", "contents": "Swine aortic smooth muscle in tissue culture. Some effects of purified swine lipoproteins on cell growth and morphology. Smooth muscle cells (SMC) were grown from inner media explants of swine aorta and used as a model for studying the role of lipoproteins in atherogenesis. These cultured cells retain the characteristics of SMC through multiple passages. Cell growth curves, in time, were obtained by using standard counting techniques, SMC grew slowly (0.019 cycle/day) in modified Dulbecco-Vogt medium supplemented with 1.5% swine serum. Purified lipoproteins were prepared from three normolipidemic and two hyperlipidemic (cholesterol-fed) swine. When the medium of 84 growth experiments was supplemented with these lipoproteins, SMC growth rate increased linearly with lipoprotein cholesterol concentration up to 10 mg/dl. At 10 mg/dl of lipoprotein cholesterol, very low density lipoproteins (VLDL) increased growth rate 7.2-fold (P less than 0.01); low density lipoproteins (LDL) 5.7-fold (P less than 0.01); high density lipoproteins (HDL2) 3,4-fold (P less than 0.02); and HDLc, and lipoprotein appearing in the hyperlipidemic swine, 3.0-fold (P less than 0.01). Addition of 10% lipoprotein-free serum stimulated growth rate 6.0-fold (P less than 0.01). There was no difference between normo- and hyperlipidemic lipoproteins with respect to cell growth rate. Factors present in the ultracentrifugal bottom, and factors appearing during the platelet release reaction, were shown to contribute to the SMC growth response. Morphological alterations characteristic of intimal foam cells occurred in SMC grown in VLDL at triglyceride levels in excess of 15 mg per 100 ml. Thus there are distinct parallels between SMC response in this model in vitro and atherogenesis in vivo."} {"id": "PMID:182414", "title": "The effect of severe trauma on urinary cyclic AMP in children of different ages.", "content": "Under routine clinical conditions the urinary excretion of cyclic AMP was studied in 97 healthy children (3 months to 16 years old) and 65 child victims of various forms of trauma and proved to be age-dependent. The mean admission cAMP urinry levels for children of all ages were increased by 44.8% and were time dependent. In 26 injured children (3 months to 9.5 years old) the excretion increased to 12.10 +/-1.29 mumol cAMP/g creatinine as compared to 8.06 +/- 2.25 mumol cAMP/g crEAtinine (50.0%; P less than 0.01) and in 38 children (9.5-16 years) it rose to 6.43 +/- 4.12 from 4.72 mumol +/- 1.10 (36.2%; P less than 0.001). In 23 victims admitted within the first two hours after trauma the cAMP levels were elevated by 31.25% in contrast to 49.2% elevation in those admitted from 2 to 24 h after trauma. In a five-day follow-up of a group of 15 surviving patients the highest excretion of cAMP was found on the first day. It was followed by a steep decline until the values plateaued on the third day at values slightly elevated above control. Compared with the fifth day, the first day excretion expressed as mumol cAMP/24 h was enhanced by 92.3% (P less than 0.01) and as a ratio to creatinine (muol/g creatine) by 52.24% (P less than 0.05. In comparison with injured adults studied previously under analogical conditions, the cAMP excretory response to trauma in children differs in higher intensity (P less than 0.01) and in the nature of the daily pattern starting with the third day. It is pointed out that the intensity of the cAMP response to pathological stimuli may be age-dependent also in other clinical conditions.", "contents": "The effect of severe trauma on urinary cyclic AMP in children of different ages. Under routine clinical conditions the urinary excretion of cyclic AMP was studied in 97 healthy children (3 months to 16 years old) and 65 child victims of various forms of trauma and proved to be age-dependent. The mean admission cAMP urinry levels for children of all ages were increased by 44.8% and were time dependent. In 26 injured children (3 months to 9.5 years old) the excretion increased to 12.10 +/-1.29 mumol cAMP/g creatinine as compared to 8.06 +/- 2.25 mumol cAMP/g crEAtinine (50.0%; P less than 0.01) and in 38 children (9.5-16 years) it rose to 6.43 +/- 4.12 from 4.72 mumol +/- 1.10 (36.2%; P less than 0.001). In 23 victims admitted within the first two hours after trauma the cAMP levels were elevated by 31.25% in contrast to 49.2% elevation in those admitted from 2 to 24 h after trauma. In a five-day follow-up of a group of 15 surviving patients the highest excretion of cAMP was found on the first day. It was followed by a steep decline until the values plateaued on the third day at values slightly elevated above control. Compared with the fifth day, the first day excretion expressed as mumol cAMP/24 h was enhanced by 92.3% (P less than 0.01) and as a ratio to creatinine (muol/g creatine) by 52.24% (P less than 0.05. In comparison with injured adults studied previously under analogical conditions, the cAMP excretory response to trauma in children differs in higher intensity (P less than 0.01) and in the nature of the daily pattern starting with the third day. It is pointed out that the intensity of the cAMP response to pathological stimuli may be age-dependent also in other clinical conditions."} {"id": "PMID:182415", "title": "Apolipoprotein of the low density lipoprotein of human plasma: structural study in familial hyperbetalipoproteinemia.", "content": "Isolation of the low density lipoprotein (LDL) from human plasma was accomplished within a narrow density interval (1.030-1.045 g/ml). After covalent modification by maleic anhydride of the protein moiety and delipidation it was possible to fractionate, by ion-exchange chromatography, up to 35% of the protein into three peptides with distinctive amino acid compositions. These fractions appeared to be identical in normal individuals and in patients with familial hyperbetalipoproteinemia (FH). Our findings provide further evidence that in FH the abnormal catabolism of the protein moiety of LDL is not related to a modification of its structure.", "contents": "Apolipoprotein of the low density lipoprotein of human plasma: structural study in familial hyperbetalipoproteinemia. Isolation of the low density lipoprotein (LDL) from human plasma was accomplished within a narrow density interval (1.030-1.045 g/ml). After covalent modification by maleic anhydride of the protein moiety and delipidation it was possible to fractionate, by ion-exchange chromatography, up to 35% of the protein into three peptides with distinctive amino acid compositions. These fractions appeared to be identical in normal individuals and in patients with familial hyperbetalipoproteinemia (FH). Our findings provide further evidence that in FH the abnormal catabolism of the protein moiety of LDL is not related to a modification of its structure."} {"id": "PMID:182416", "title": "Radioimmunoassay for human plasma apolipoprotein B.", "content": "We have developed a simplified double antibody radioimmunoassay for human apolipoprotein beta. The purified antigen, a narrow density subclass of beta lipoprotein (d 1.030-1.050 g/ml; was isolated by a combination of gel filtration and ultracentrifugationmthis material gave a single immunoprecipitin arc on crossed immunoelectrophoresis into an antibody to whole human serum. The antigen was radiolabelled using iodine monochloride at pH 10. The iodinated antigen was indistinguishable immunochemically from native material and eluted as a single radioactive peak from a Sephadex G-200 column. The lower limit of sensitivity of the assay was 15 ng protein, and the working range, 15-200 ng. The mean apolipoprotein B level (+/-1 S.D.) in 128 healthy control subjects was 86.6 +/- 29.6 mg/100ml and is in agreement the values published by other workers using unmodified assays.", "contents": "Radioimmunoassay for human plasma apolipoprotein B. We have developed a simplified double antibody radioimmunoassay for human apolipoprotein beta. The purified antigen, a narrow density subclass of beta lipoprotein (d 1.030-1.050 g/ml; was isolated by a combination of gel filtration and ultracentrifugationmthis material gave a single immunoprecipitin arc on crossed immunoelectrophoresis into an antibody to whole human serum. The antigen was radiolabelled using iodine monochloride at pH 10. The iodinated antigen was indistinguishable immunochemically from native material and eluted as a single radioactive peak from a Sephadex G-200 column. The lower limit of sensitivity of the assay was 15 ng protein, and the working range, 15-200 ng. The mean apolipoprotein B level (+/-1 S.D.) in 128 healthy control subjects was 86.6 +/- 29.6 mg/100ml and is in agreement the values published by other workers using unmodified assays."} {"id": "PMID:182417", "title": "Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency.", "content": "Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5-6 mg/dl and mean initial serum magnesium concentration was 0-75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (less than 150 pg/ml) or normal (less than 550 pg/ml) in all but two patients. Serial measurements made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144-300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30-60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end-organ resistance to PTH in these patients. The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the same patients by measurement of plasma cyclic AMP concentrations following administration of glucagon, normal increases were observed. These results suggest that adenylate cyclase systems of various organs may be affected differentially by a state of magnesium deficiency. It is suggested that magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs. This could be the principal mechanism operative in both impaired PTH secretion and end-organ resistance to PTH which together contribute to the development of hypocalcaemia.", "contents": "Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5-6 mg/dl and mean initial serum magnesium concentration was 0-75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (less than 150 pg/ml) or normal (less than 550 pg/ml) in all but two patients. Serial measurements made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144-300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30-60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end-organ resistance to PTH in these patients. The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the same patients by measurement of plasma cyclic AMP concentrations following administration of glucagon, normal increases were observed. These results suggest that adenylate cyclase systems of various organs may be affected differentially by a state of magnesium deficiency. It is suggested that magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs. This could be the principal mechanism operative in both impaired PTH secretion and end-organ resistance to PTH which together contribute to the development of hypocalcaemia."} {"id": "PMID:182420", "title": "Starvation in man.", "content": "Starvation entails a progressive selection of fat as body fuel. Soon after a meal glucose utilisation by muscle ceases and fatty acids are used instead. Ketoacid levels in blood become elevated over the first week, and the brain preferentially uses these instead of glucose. The net effect is to spare protein even further, as glucose utilisation by brain is diminished. Nevertheless, there is still net negative nitrogen balance, but this can be nullified by amino acid or protein supplementation. Insulin appears to be the principal regulatory hormone. Recent data suggest that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs.", "contents": "Starvation in man. Starvation entails a progressive selection of fat as body fuel. Soon after a meal glucose utilisation by muscle ceases and fatty acids are used instead. Ketoacid levels in blood become elevated over the first week, and the brain preferentially uses these instead of glucose. The net effect is to spare protein even further, as glucose utilisation by brain is diminished. Nevertheless, there is still net negative nitrogen balance, but this can be nullified by amino acid or protein supplementation. Insulin appears to be the principal regulatory hormone. Recent data suggest that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs."} {"id": "PMID:182421", "title": "Adenine arabinoside (ARA-A) blocked HSV-2 infected human skin fibroblasts as targets for the detection of serum mediated and cellular cytotoxicity in patients with cervical carcinoma.", "content": "Human skin fibroblasts remained viable after infection with herpes simplex virus type 2 (HSV-2) if grown after infection in the presence of adenine arabinoside (ARA-A); The cells were specifically killed by normal human lymphoid cells in the presence of HSV-2 convalescent or rabbit immune serum, and this cytotoxicity could be blocked by a crude HSV-2 antigen preparation. Antibodies capable of mediating such cytotoxicity against HSV-2 induced cell surface antigens could be detected in four out of eleven patients with carcinoma of the uterine cervix. Ten patients were tested for the presence of direct cellular cytotoxicity against HSV-2 infected, ARA-A blocked target cells and none was found.", "contents": "Adenine arabinoside (ARA-A) blocked HSV-2 infected human skin fibroblasts as targets for the detection of serum mediated and cellular cytotoxicity in patients with cervical carcinoma. Human skin fibroblasts remained viable after infection with herpes simplex virus type 2 (HSV-2) if grown after infection in the presence of adenine arabinoside (ARA-A); The cells were specifically killed by normal human lymphoid cells in the presence of HSV-2 convalescent or rabbit immune serum, and this cytotoxicity could be blocked by a crude HSV-2 antigen preparation. Antibodies capable of mediating such cytotoxicity against HSV-2 induced cell surface antigens could be detected in four out of eleven patients with carcinoma of the uterine cervix. Ten patients were tested for the presence of direct cellular cytotoxicity against HSV-2 infected, ARA-A blocked target cells and none was found."} {"id": "PMID:182422", "title": "Leucocyte capillary migration: an adherence dependent phenomenon.", "content": "To determine the mode of action of leucocyte inhibitory factor (LIF) on polymorphonuclear leucocyte (PMN) migration out of capillary tubes, this phenomenon has been compared with PMN adhesion to cotton wool columns. Colchicine and vinblastine sulphate had no effect on either of these processes but cytochalasin B caused marked inhibition of PMN migration and increased PMN adhesion. The cytochalasin B effect could be reversed in the presence of drugs known to increase intracellular levels of cyclic AMP. For inhibition of PMN migration by LIF, Mg2+ but not Ca2+ was essential. LIF not only inhibited PMN migration but also increased PMN adhesion to cotton wool columns. LIF inhibitory activity on PMN migration was not affected by colchicine or vinblastine. Leucocyte migration and adhesion depend on similar mechanisms, and are both influenced by LIF which probably acts by affecting micro-filament function.", "contents": "Leucocyte capillary migration: an adherence dependent phenomenon. To determine the mode of action of leucocyte inhibitory factor (LIF) on polymorphonuclear leucocyte (PMN) migration out of capillary tubes, this phenomenon has been compared with PMN adhesion to cotton wool columns. Colchicine and vinblastine sulphate had no effect on either of these processes but cytochalasin B caused marked inhibition of PMN migration and increased PMN adhesion. The cytochalasin B effect could be reversed in the presence of drugs known to increase intracellular levels of cyclic AMP. For inhibition of PMN migration by LIF, Mg2+ but not Ca2+ was essential. LIF not only inhibited PMN migration but also increased PMN adhesion to cotton wool columns. LIF inhibitory activity on PMN migration was not affected by colchicine or vinblastine. Leucocyte migration and adhesion depend on similar mechanisms, and are both influenced by LIF which probably acts by affecting micro-filament function."} {"id": "PMID:182429", "title": "Colestipol in familial type II hyperlipoproteinemia: a three-year trial.", "content": "Colestipol, a new bile acid sequestrant polymer, has been shown to lower the serum cholesterol level more than 30% in 13 patients with familial type II hyperlipoproteinemia. Placebo for 6 wk was followed by colestipol for periods up to 36 mo. A slight but not significant increase of serum triglyceride concentrations was observed during the first 18 no, but they returned to values under the baseline level thereafter. No signs of impaired intestinal fat resorption were noted. Side effects were primarily gastrointestinal (mild and transient constipation). Colestipol seems to be an effective and safe drug in the treatment of the famiial type II hyperlipoproteinemia, without escape phenonmenon.", "contents": "Colestipol in familial type II hyperlipoproteinemia: a three-year trial. Colestipol, a new bile acid sequestrant polymer, has been shown to lower the serum cholesterol level more than 30% in 13 patients with familial type II hyperlipoproteinemia. Placebo for 6 wk was followed by colestipol for periods up to 36 mo. A slight but not significant increase of serum triglyceride concentrations was observed during the first 18 no, but they returned to values under the baseline level thereafter. No signs of impaired intestinal fat resorption were noted. Side effects were primarily gastrointestinal (mild and transient constipation). Colestipol seems to be an effective and safe drug in the treatment of the famiial type II hyperlipoproteinemia, without escape phenonmenon."} {"id": "PMID:182426", "title": "Malignant fibrous histiocytoma associated with bone infarcts: report of a case.", "content": "A caisson worker with symmetrical bone infarcts in the tibiae demonstrated a malignant transformation of one of the bone infarcts with wide-spread metastases to the lungs and viscera. Histologically, the tumor was found to be a malignant fibrous histiocytoma and despite amputation, the patient died approximately one year following the diagnosis. This case lends credence to the concept of a cause and effect relationship existing between bone infarcts and the subsequent development of bone sarcoma.", "contents": "Malignant fibrous histiocytoma associated with bone infarcts: report of a case. A caisson worker with symmetrical bone infarcts in the tibiae demonstrated a malignant transformation of one of the bone infarcts with wide-spread metastases to the lungs and viscera. Histologically, the tumor was found to be a malignant fibrous histiocytoma and despite amputation, the patient died approximately one year following the diagnosis. This case lends credence to the concept of a cause and effect relationship existing between bone infarcts and the subsequent development of bone sarcoma."} {"id": "PMID:182427", "title": "Tumors associated with metallic implants in animals.", "content": "Eight cases of malignant tumors originating in close proximity to various metallic surgical implants which were used in the treatment of common canine and feline fractures are presented. There were 5 osteosarcomas, one fibrosarcoma and 2 undifferentiated sarcomas with the characterisitcs of malignant histiocytomas. All 8 occurred in the md shaft of the femur, humerus or radius, a most unusual location considering that almost all primary canine osteosarcomas have been found tramedullary pins, 2 with intramedullary Steinmann pins (one with cerclage wires) and one with an AO plate screws. Seven of the fractures treated had united and only one pseudoarthrosis was present where the cerclage wires were used. All implants used showed corrosion and had been in place for 6 months to 6 years prior to tumor discovery. None was infected.", "contents": "Tumors associated with metallic implants in animals. Eight cases of malignant tumors originating in close proximity to various metallic surgical implants which were used in the treatment of common canine and feline fractures are presented. There were 5 osteosarcomas, one fibrosarcoma and 2 undifferentiated sarcomas with the characterisitcs of malignant histiocytomas. All 8 occurred in the md shaft of the femur, humerus or radius, a most unusual location considering that almost all primary canine osteosarcomas have been found tramedullary pins, 2 with intramedullary Steinmann pins (one with cerclage wires) and one with an AO plate screws. Seven of the fractures treated had united and only one pseudoarthrosis was present where the cerclage wires were used. All implants used showed corrosion and had been in place for 6 months to 6 years prior to tumor discovery. None was infected."} {"id": "PMID:182431", "title": "Issues in developing quality aftercare clinics for the chronic mentally ill.", "content": "Two large aftercare clinics were established to provide treatment and rehabilitative care for a chronic mentally ill population requiring neuroleptic drugs. The clinics have evolved rapidly and expanded their service over the past 3 years but have required constant monitoring and modification in order to provide quality as well as quantity care in the community setting. These modifications are described and the importance of further community-based investigation in the rehabilitation and treatment of the chronic mentally ill is stressed.", "contents": "Issues in developing quality aftercare clinics for the chronic mentally ill. Two large aftercare clinics were established to provide treatment and rehabilitative care for a chronic mentally ill population requiring neuroleptic drugs. The clinics have evolved rapidly and expanded their service over the past 3 years but have required constant monitoring and modification in order to provide quality as well as quantity care in the community setting. These modifications are described and the importance of further community-based investigation in the rehabilitation and treatment of the chronic mentally ill is stressed."} {"id": "PMID:182432", "title": "Practical guidelines for the community treatment of markedly impaired patients.", "content": "A sound technology does not yet exist for successfully treating in the community those patients traditionally treated by public mental hospitals and aftercare programs. The current paper attempts to advance this technology by presenting practical guidelines based on the empirical work of the writers and others. Recommendations include a focus on the teaching of coping skills, an in vivo site of treatment, an assertive approach, and use of a variety of social learning techniques. Staffing and monetary needs for community treatment are also discussed.", "contents": "Practical guidelines for the community treatment of markedly impaired patients. A sound technology does not yet exist for successfully treating in the community those patients traditionally treated by public mental hospitals and aftercare programs. The current paper attempts to advance this technology by presenting practical guidelines based on the empirical work of the writers and others. Recommendations include a focus on the teaching of coping skills, an in vivo site of treatment, an assertive approach, and use of a variety of social learning techniques. Staffing and monetary needs for community treatment are also discussed."} {"id": "PMID:182434", "title": "Newer aspects of parathyroid chemistry and physiology.", "content": "We have attempted to integrate in this review many recent studies on the formation, packaging and secretion of parathormone by the parathyroid gland. We have shown that substantial new insights have been gained into this complex cellular operation. Continuing investigation should clarify many of the outstanding questions regarding function of the parathyroid in their central role in calcium homeostasis.", "contents": "Newer aspects of parathyroid chemistry and physiology. We have attempted to integrate in this review many recent studies on the formation, packaging and secretion of parathormone by the parathyroid gland. We have shown that substantial new insights have been gained into this complex cellular operation. Continuing investigation should clarify many of the outstanding questions regarding function of the parathyroid in their central role in calcium homeostasis."} {"id": "PMID:182435", "title": "Immunoglobulin concentrations and bovine enterovirus inhibitors in fetal bovine fluids.", "content": "Fluids from 53 bovine fetuses ranging in age from 90 to 240 days were examined for immunoglobulin G (IgG) and immunoglobulin M (IgM) and neutralizing activity to ten bovine viruses. Non-specific inhibitors to bovine enteroviruses were found in serum, allantoic, and amniotic fluids of most samples tested. In most cases, serum IgG were within normal values. Neither IgG nor IgM was detected in amniotic fluids, whereas 2 samples of allantoic fluid contained traces of IgG.", "contents": "Immunoglobulin concentrations and bovine enterovirus inhibitors in fetal bovine fluids. Fluids from 53 bovine fetuses ranging in age from 90 to 240 days were examined for immunoglobulin G (IgG) and immunoglobulin M (IgM) and neutralizing activity to ten bovine viruses. Non-specific inhibitors to bovine enteroviruses were found in serum, allantoic, and amniotic fluids of most samples tested. In most cases, serum IgG were within normal values. Neither IgG nor IgM was detected in amniotic fluids, whereas 2 samples of allantoic fluid contained traces of IgG."} {"id": "PMID:182436", "title": "Bone pathology in hypervitaminosis D an experimental study in young pigs.", "content": "Five groups of 4 weanling pigs were fed a diet with 1.2% calcium and 1.0% phosphorus for 8 weeks with vitamin D3 at 1, 5, 25, 125 and 625 times the recommended levels, respectively. Hypercalcemia and hypophosphatasemia developed rapidly and persisted in Group 5 and developed more slowly but steadily in Group 4. Increasing levels of vitamin D3 influenced progressively and negatively the activity of resorbing osteocytes with osteopetrosis in Groups 2 and 3 and with osteonecrosis in Group 5. Atrophy of osteoblasts further contributed to the osteopenia in Group 5. Cartilage growth activity was arrested in Group 5. The negative effect on the resorbing osteocytes, which finally lead to death of the cells, was ascribed directly to vitamin D3 toxicosis since hypoparathyroidism and hypercalcitonism, both resulting from hypercalcemia, are not known to induce osteonecrosis. Since hypercalemia was finally as severe in Group 4 as in Group 5 and since there was soft tissue calcinosis only in Group 5, the calcinosis was always considered dystrophic, an interpretation supported by the observation that degenerative histologic changes preceded soft tissue calcinosis.", "contents": "Bone pathology in hypervitaminosis D an experimental study in young pigs. Five groups of 4 weanling pigs were fed a diet with 1.2% calcium and 1.0% phosphorus for 8 weeks with vitamin D3 at 1, 5, 25, 125 and 625 times the recommended levels, respectively. Hypercalcemia and hypophosphatasemia developed rapidly and persisted in Group 5 and developed more slowly but steadily in Group 4. Increasing levels of vitamin D3 influenced progressively and negatively the activity of resorbing osteocytes with osteopetrosis in Groups 2 and 3 and with osteonecrosis in Group 5. Atrophy of osteoblasts further contributed to the osteopenia in Group 5. Cartilage growth activity was arrested in Group 5. The negative effect on the resorbing osteocytes, which finally lead to death of the cells, was ascribed directly to vitamin D3 toxicosis since hypoparathyroidism and hypercalcitonism, both resulting from hypercalcemia, are not known to induce osteonecrosis. Since hypercalemia was finally as severe in Group 4 as in Group 5 and since there was soft tissue calcinosis only in Group 5, the calcinosis was always considered dystrophic, an interpretation supported by the observation that degenerative histologic changes preceded soft tissue calcinosis."} {"id": "PMID:182439", "title": "Use of cell cultures with persistent virus infections to test the efficacy of antiviral compounds.", "content": "BHK-21 cells persistently infected with either vaccinia or foot and mouth disease virus were used to study the efficacy of antiviral compounds. The results of the persistent infection cell culture (PICC) test were compared with those obtained by the plaque reduction (PR) test. The comparison showed that: (1) the PICC test is more informative than the PR test; (2) stimulative as well as inhibitory activities of compounds are detectable, and (3) since the PICC test can be carried on for several weeks or even months this test is especially well suited to study the problem of drug resistance in cell cultures.", "contents": "Use of cell cultures with persistent virus infections to test the efficacy of antiviral compounds. BHK-21 cells persistently infected with either vaccinia or foot and mouth disease virus were used to study the efficacy of antiviral compounds. The results of the persistent infection cell culture (PICC) test were compared with those obtained by the plaque reduction (PR) test. The comparison showed that: (1) the PICC test is more informative than the PR test; (2) stimulative as well as inhibitory activities of compounds are detectable, and (3) since the PICC test can be carried on for several weeks or even months this test is especially well suited to study the problem of drug resistance in cell cultures."} {"id": "PMID:182445", "title": "[Sitosterol in familial hyperlipoproteinemia type II. A randomized double-blind cross-over study].", "content": "The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient.", "contents": "[Sitosterol in familial hyperlipoproteinemia type II. A randomized double-blind cross-over study]. The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient."} {"id": "PMID:182446", "title": "[Poliomyelitis in the German Federal Republic 1974-1975 (author's transl)].", "content": "The virological surveillance of poliomyelitis in 1974-1975 led to the detection of specific characteristics of wild viruses in 57 out of 221 cases of poliovirus isolation. The disease symptoms were typical for poliomyelitis in 36 of these cases, less characteristic in 13. Polio wildvirus was isolated 8 times from the surroundings of the patients. In 36 foreign patients and one German the causative agent was imported from an endemic area. In these cases and in a further 7 German patients the disease was sporadic. In contrast 5 cases in German children in late autumn 1975 constitute a local epidemic of poliomyelitis.", "contents": "[Poliomyelitis in the German Federal Republic 1974-1975 (author's transl)]. The virological surveillance of poliomyelitis in 1974-1975 led to the detection of specific characteristics of wild viruses in 57 out of 221 cases of poliovirus isolation. The disease symptoms were typical for poliomyelitis in 36 of these cases, less characteristic in 13. Polio wildvirus was isolated 8 times from the surroundings of the patients. In 36 foreign patients and one German the causative agent was imported from an endemic area. In these cases and in a further 7 German patients the disease was sporadic. In contrast 5 cases in German children in late autumn 1975 constitute a local epidemic of poliomyelitis."} {"id": "PMID:182449", "title": "Interaction between thyroid hormones and erythrocyte membranes: competitive inhibition of binding 131 I-L-triiodothyronine and 131 I-L-thyroxine by their analogs.", "content": "Molecular structural characteristics of thyroid hormones which influence binding to the erythrocyte membranes were investigated by competitive binding experiments. The ability of thyroid hormone analogs to displace 131 I-L-thyroxine and 131 I-L-triiodothyronine from the membranes was considered evidence of their competitive binding. The diphenyl ether linkage (thyronine) was essential as compounds with a single aromatic ring were weakly competitive. The presence of three iodine atoms at 3, 5 and 3' positions on thyronine was optimal for maximal competitive binding. There was weak competitive binding of analogs if chlorine or bromine was substituted for iodine. The alanine side chain was required for optimal binding as N-acetyl-l-thyroxine and various deaminated analogs were poor competitors compared to T4 and T3. L-isomers of T4 and T3 showed greater competitive binding to erythrocyte membranes than the corresponding d-isomers.", "contents": "Interaction between thyroid hormones and erythrocyte membranes: competitive inhibition of binding 131 I-L-triiodothyronine and 131 I-L-thyroxine by their analogs. Molecular structural characteristics of thyroid hormones which influence binding to the erythrocyte membranes were investigated by competitive binding experiments. The ability of thyroid hormone analogs to displace 131 I-L-thyroxine and 131 I-L-triiodothyronine from the membranes was considered evidence of their competitive binding. The diphenyl ether linkage (thyronine) was essential as compounds with a single aromatic ring were weakly competitive. The presence of three iodine atoms at 3, 5 and 3' positions on thyronine was optimal for maximal competitive binding. There was weak competitive binding of analogs if chlorine or bromine was substituted for iodine. The alanine side chain was required for optimal binding as N-acetyl-l-thyroxine and various deaminated analogs were poor competitors compared to T4 and T3. L-isomers of T4 and T3 showed greater competitive binding to erythrocyte membranes than the corresponding d-isomers."} {"id": "PMID:182450", "title": "Failure of 1, 25 dihydroxycholecalciferol (1, 25-(OH) 2-D3) to modify cyclic AMP levels in parathyroid hormone-treated and untreated bone cells.", "content": "Treatment with 1, 25-(OH) 2-D3 (1 ng/ml-25 ng/ml) for periods ranging from 2.5 min. to 60 min. did not alter cyclic AMP levels in bone cells isolated from periosteum-free rat calvaria, or in cells isolated from rat periosteal tissues. 1, 25-(OH) 2-D3 failed to modify the acute increases in cyclic AMP elicited by PTH (10 ng/ml-1 ug/ml). Two separate 1, 25-(OH) 2-D3 preparations, biologically active in other systems, were ineffective under a wide variety of experimental conditions. These results suggest that 1, 25-(OH) 2-D3 is not an acute modulator of cyclic AMP metabolism in PTH-treated and untreated bone cells.", "contents": "Failure of 1, 25 dihydroxycholecalciferol (1, 25-(OH) 2-D3) to modify cyclic AMP levels in parathyroid hormone-treated and untreated bone cells. Treatment with 1, 25-(OH) 2-D3 (1 ng/ml-25 ng/ml) for periods ranging from 2.5 min. to 60 min. did not alter cyclic AMP levels in bone cells isolated from periosteum-free rat calvaria, or in cells isolated from rat periosteal tissues. 1, 25-(OH) 2-D3 failed to modify the acute increases in cyclic AMP elicited by PTH (10 ng/ml-1 ug/ml). Two separate 1, 25-(OH) 2-D3 preparations, biologically active in other systems, were ineffective under a wide variety of experimental conditions. These results suggest that 1, 25-(OH) 2-D3 is not an acute modulator of cyclic AMP metabolism in PTH-treated and untreated bone cells."} {"id": "PMID:182451", "title": "Regulation of cyclic adenosine 3', 5' -mono-phosphate dependent protein kinase of rat ovarian cells by luteinizing hormone and human chorionic gonadotropin.", "content": "Regulation of cAMP dependent protein kinase activity from rat ovarian cells has been studied in response to luteinizing hormone and human chorionic gonadotropin. Treatment of cells with human chorionic gonadotropin in concentration range of 2.5ng-1000ng/ml resulted in increased accumulation of cAMP,activation of protein kinase followed by the stimulation of progesterone synthesis. A sixfold increase in the activity ratio, defined as the ratio of protein kinase stimulated in situ to that maximally stimulated in vitro by exogenous cAMP, was observed with 1ug/ml of hCG. This concentration of hormone also produced a ten-fold increase in cAMP and a thirty-to forty-fold increase in progesterone synthesis. Protein kinase activation was specific for LH and hCG, as other polypeptide hormones were without any appreciable effect. The stimulation of protein kinase persisted even after the elevated cAMP level began to fall. It appears that the activation of protein kinase is an obligatory early event that mediates an increase in gonadotropin stimulated progesterone synthesis.", "contents": "Regulation of cyclic adenosine 3', 5' -mono-phosphate dependent protein kinase of rat ovarian cells by luteinizing hormone and human chorionic gonadotropin. Regulation of cAMP dependent protein kinase activity from rat ovarian cells has been studied in response to luteinizing hormone and human chorionic gonadotropin. Treatment of cells with human chorionic gonadotropin in concentration range of 2.5ng-1000ng/ml resulted in increased accumulation of cAMP,activation of protein kinase followed by the stimulation of progesterone synthesis. A sixfold increase in the activity ratio, defined as the ratio of protein kinase stimulated in situ to that maximally stimulated in vitro by exogenous cAMP, was observed with 1ug/ml of hCG. This concentration of hormone also produced a ten-fold increase in cAMP and a thirty-to forty-fold increase in progesterone synthesis. Protein kinase activation was specific for LH and hCG, as other polypeptide hormones were without any appreciable effect. The stimulation of protein kinase persisted even after the elevated cAMP level began to fall. It appears that the activation of protein kinase is an obligatory early event that mediates an increase in gonadotropin stimulated progesterone synthesis."} {"id": "PMID:182452", "title": "Cytoplasmic glucocorticoid receptors in the developing small intestine of the rabbit fetus.", "content": "Glucocorticoid binding and alkaline phosphatase activity in the small intestine of the fetal rabbit were studied to investigate the relationship of glucocorticoid receptors and the development of the tissue. In the cytosol fraction, the binding of (3H)dexamethasone involves a macromolecule with high affinity (Kd = nM) for the hormone and a limited number of binding sites (saturable at a hormone concentration of 10 nM). That the binding reaction involves a protein and sulfhydryl groups was demonstrated by the absence of binding of the steroid in the presence of Pronase and sulfhydryl blocking reagents. In sucrose density gradients, the complexes have sedimentation coefficients of about 4S and 7S at low ionic strength, but only 4S at high ionic strength (0.4m KCl). The binding protein is thermolabile, and is stabilized by complexing with the hormone. The ability of different steroids to compete with (3H)dexamethasone for the binding sites correlates well with their glucocorticoid potency. During development of the fetal rabbit small intestine, the total number of glucocorticoid-binding sites in the cytosol increases in parallel with the increases in the tissue weight until term. However, the concentration of the binding sites (pmol/mg cytosol protein) is maximum at day 25 of gestation, followed by a decrease to the adult level within a few days after birth. Alkaline phosphatase activity is first detectable on day 25 of gestation and increases rapidly thereafter. These observations suggest that there may be a temporal relatioship between the development of the fetal rabbit small intestine, as reflected in the alkaline phosphatase and the levels of glucocorticoid receptors in the cytosol.", "contents": "Cytoplasmic glucocorticoid receptors in the developing small intestine of the rabbit fetus. Glucocorticoid binding and alkaline phosphatase activity in the small intestine of the fetal rabbit were studied to investigate the relationship of glucocorticoid receptors and the development of the tissue. In the cytosol fraction, the binding of (3H)dexamethasone involves a macromolecule with high affinity (Kd = nM) for the hormone and a limited number of binding sites (saturable at a hormone concentration of 10 nM). That the binding reaction involves a protein and sulfhydryl groups was demonstrated by the absence of binding of the steroid in the presence of Pronase and sulfhydryl blocking reagents. In sucrose density gradients, the complexes have sedimentation coefficients of about 4S and 7S at low ionic strength, but only 4S at high ionic strength (0.4m KCl). The binding protein is thermolabile, and is stabilized by complexing with the hormone. The ability of different steroids to compete with (3H)dexamethasone for the binding sites correlates well with their glucocorticoid potency. During development of the fetal rabbit small intestine, the total number of glucocorticoid-binding sites in the cytosol increases in parallel with the increases in the tissue weight until term. However, the concentration of the binding sites (pmol/mg cytosol protein) is maximum at day 25 of gestation, followed by a decrease to the adult level within a few days after birth. Alkaline phosphatase activity is first detectable on day 25 of gestation and increases rapidly thereafter. These observations suggest that there may be a temporal relatioship between the development of the fetal rabbit small intestine, as reflected in the alkaline phosphatase and the levels of glucocorticoid receptors in the cytosol."} {"id": "PMID:182453", "title": "Testosterone-binding protein in reproductive tracts of fetal rats.", "content": "Testosterone-binding proteins may mediate the induction of Wolffian duct differentiation by testicular testosterone. The presence of such protein(s) was sought in reproductive tracts of 14.5-21.5-day-old fetal rats. Supernatant fractions (127,000 x g) were equilibrated with [3H]T) +/- radioinert testosterone in Tris - HCl:EDTA buffer, pH 7.4, (approximately 0.1 mg protein/0.5 ml) at 4 C for 16 hours. Bound and free (3H)T were separated by charcoaldextran adsorption or Sephadex G-100 gel filtration. The results with 14.5-15.0-day-old tracts were: a) specific binding to protein was saturated with increasing (3H)T concentration; b) Scatchard plot analysis indicated the presence of a single class of binding sites with high affinity (apparent Kd = 2 nM) and limited capacity (approximately 16 fmol/mg protein) for (3H)T; c) specific uptake was limited to (3H)T and (3H)5 alpha-dihydrotestosterone; d) (3H)T uptake by the tract supernatant was tissue-specific; e) pronase treatment abolished binding capacity for (3H)T; f) bound radioactivity consisted solely of (3H)T; and g) the mesonephric and ductal segment of the genital tract specifically binds (3H)T. The data demonstrate binding protein(s), specific for testosterone and possibly dihydrotestosterone, in the genital ducts of 14.5-15-day-old fetal rats. (3H)T binding to genital duct supernatants from male but not from female fetuses increased about 5-fold between 14.5 and 20.5 days of gestation. Upon Sephadex G-100 gel filtration, radioactivity was confined to the macromolecular fraction appearing in the void volume. Nuclear fractions, obtained from intact ducts incubated with (3H)T at 30 C but not at 0 C contained radioactivity. These observations are compatible with the existence of a cytoplasmic testosterone receptor or carrier protein aggregate. We have thus concluded that testosterone-binding proteins are present in the genital ducts of rat fetuses and that, in the male, their concentrations increase with progressive Wolffian duct differentiation.", "contents": "Testosterone-binding protein in reproductive tracts of fetal rats. Testosterone-binding proteins may mediate the induction of Wolffian duct differentiation by testicular testosterone. The presence of such protein(s) was sought in reproductive tracts of 14.5-21.5-day-old fetal rats. Supernatant fractions (127,000 x g) were equilibrated with [3H]T) +/- radioinert testosterone in Tris - HCl:EDTA buffer, pH 7.4, (approximately 0.1 mg protein/0.5 ml) at 4 C for 16 hours. Bound and free (3H)T were separated by charcoaldextran adsorption or Sephadex G-100 gel filtration. The results with 14.5-15.0-day-old tracts were: a) specific binding to protein was saturated with increasing (3H)T concentration; b) Scatchard plot analysis indicated the presence of a single class of binding sites with high affinity (apparent Kd = 2 nM) and limited capacity (approximately 16 fmol/mg protein) for (3H)T; c) specific uptake was limited to (3H)T and (3H)5 alpha-dihydrotestosterone; d) (3H)T uptake by the tract supernatant was tissue-specific; e) pronase treatment abolished binding capacity for (3H)T; f) bound radioactivity consisted solely of (3H)T; and g) the mesonephric and ductal segment of the genital tract specifically binds (3H)T. The data demonstrate binding protein(s), specific for testosterone and possibly dihydrotestosterone, in the genital ducts of 14.5-15-day-old fetal rats. (3H)T binding to genital duct supernatants from male but not from female fetuses increased about 5-fold between 14.5 and 20.5 days of gestation. Upon Sephadex G-100 gel filtration, radioactivity was confined to the macromolecular fraction appearing in the void volume. Nuclear fractions, obtained from intact ducts incubated with (3H)T at 30 C but not at 0 C contained radioactivity. These observations are compatible with the existence of a cytoplasmic testosterone receptor or carrier protein aggregate. We have thus concluded that testosterone-binding proteins are present in the genital ducts of rat fetuses and that, in the male, their concentrations increase with progressive Wolffian duct differentiation."} {"id": "PMID:182454", "title": "1alpha,25-dihydroxyvitamin D3-like component present in the plant Solanum glaucophyllum.", "content": "The ability of an aqueous extract prepared from dried leaves of the South American shrub Solanum glaucophyllum to interact with a chick intestinal receptor system highly specific for the biologically active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), was monitored under both in vivo and in vitro conditions. The pretreatment of chicks with the S. glaucophyllum extract reduced the amount of subsequently administered radioactive 1alpha, 25-dihydroxyvitamin D3 localized in the intestinal chromatin fraction by 90% when compared with vitamin D-deficient controls. In addition, the active principle in the aqueous extract was found to compete effectively with 1alpha, 25-(OH)2D3 in a reconstituted intestinal receptor system in vitro. The plant factor(s) was found to be as effective as 1alpha, 25-(OH)2D3 in decreasing the renal 25-hydroxycholecalciferol-1alpha hydroxylase activity levels when administered to vitamin D-deficient chicks. By means of the in vitro intestinal receptor assay, it was possible to estimate that there are approximately 10 to 60 mg of the biologically active material in one kilogram of dries S. glaucophyllum leaves. These data indicate that the plant factor(s) may be a structural analog of 1alpha, 25-(OH)2D3 and suggest the feasibility of its isolation.", "contents": "1alpha,25-dihydroxyvitamin D3-like component present in the plant Solanum glaucophyllum. The ability of an aqueous extract prepared from dried leaves of the South American shrub Solanum glaucophyllum to interact with a chick intestinal receptor system highly specific for the biologically active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), was monitored under both in vivo and in vitro conditions. The pretreatment of chicks with the S. glaucophyllum extract reduced the amount of subsequently administered radioactive 1alpha, 25-dihydroxyvitamin D3 localized in the intestinal chromatin fraction by 90% when compared with vitamin D-deficient controls. In addition, the active principle in the aqueous extract was found to compete effectively with 1alpha, 25-(OH)2D3 in a reconstituted intestinal receptor system in vitro. The plant factor(s) was found to be as effective as 1alpha, 25-(OH)2D3 in decreasing the renal 25-hydroxycholecalciferol-1alpha hydroxylase activity levels when administered to vitamin D-deficient chicks. By means of the in vitro intestinal receptor assay, it was possible to estimate that there are approximately 10 to 60 mg of the biologically active material in one kilogram of dries S. glaucophyllum leaves. These data indicate that the plant factor(s) may be a structural analog of 1alpha, 25-(OH)2D3 and suggest the feasibility of its isolation."} {"id": "PMID:182455", "title": "Stimulation of testosterone production in isolated rabbit thecal tissue by LH/FSH, dibutyryl cyclic AMP, PGE2alpha, and PGE2.", "content": "The capacities of isolated rabbit theca and granulosa cells to secrete testosterone were studied in vitro. Large Graafian follicles (1-1.5 mm in diameter) were dissected intact from the ovaries of adult estrous rabbits. Granulosa cells from 4 follicles (50,000 cells) and theca tissue (16 pieces per dish, equivalent to 4 follicles) were cultured separately for 6 days either as controls (without exogenous hormones) or with one of the following agents: 1 lU/ml LH/FSH (Pergonal), 10-3M dibutyryl cyclic AMP (Bu2cAMP), 1 mug/ml prostaglandin F2alpha (PGF2alpha), or 1 mug/ml prostaglandin E2 (PGE2). The media were collected every 2 days, and the testosterone (T) was measured by radioimmunoassay. The control cultures of granulosa cells secreted small amounts of T (700 +/- 317 pg/culture: mean +/-SE) during the first 2 days in vitro, and the addition of LH/FSH, Bu2cAMP, PGF2alpha, or PGE2 did not significantly stimulate T production. After 2 days in vitro, very little T (greater than 200 pg/culture) was produced by control and prostaglandin-treated granulosa cells, whereas those incubated with LH/FSH and Bu2cAMP maintained their initial T production rates. Theca control cultures produced 3 +/- 0.4 ng of T (mean +/- SE) during the first 2 days in 13.6-fold by LH/FSH, 3.6-fold by Bu2cAMP, and 3-fold by PGF2alpha and PGE2- T was not detected in theca cultures after 2 days except in those treated with LH/FSH or Bu2cAMP, which produced 1.5 +/- 0.5 and 1.6 +/- 0.3 ng of T, respectively, at 4 days (mean +/- SE). These results suggest that under the present conditions, pieces of rabbit thecal tissue have a greater capacity to produce T de novo than do isolated granulosa cells, and indicate that T production is transiently stimulated by LH/FSH, Bu2cAMP, PGE2alpha, and PGE2.", "contents": "Stimulation of testosterone production in isolated rabbit thecal tissue by LH/FSH, dibutyryl cyclic AMP, PGE2alpha, and PGE2. The capacities of isolated rabbit theca and granulosa cells to secrete testosterone were studied in vitro. Large Graafian follicles (1-1.5 mm in diameter) were dissected intact from the ovaries of adult estrous rabbits. Granulosa cells from 4 follicles (50,000 cells) and theca tissue (16 pieces per dish, equivalent to 4 follicles) were cultured separately for 6 days either as controls (without exogenous hormones) or with one of the following agents: 1 lU/ml LH/FSH (Pergonal), 10-3M dibutyryl cyclic AMP (Bu2cAMP), 1 mug/ml prostaglandin F2alpha (PGF2alpha), or 1 mug/ml prostaglandin E2 (PGE2). The media were collected every 2 days, and the testosterone (T) was measured by radioimmunoassay. The control cultures of granulosa cells secreted small amounts of T (700 +/- 317 pg/culture: mean +/-SE) during the first 2 days in vitro, and the addition of LH/FSH, Bu2cAMP, PGF2alpha, or PGE2 did not significantly stimulate T production. After 2 days in vitro, very little T (greater than 200 pg/culture) was produced by control and prostaglandin-treated granulosa cells, whereas those incubated with LH/FSH and Bu2cAMP maintained their initial T production rates. Theca control cultures produced 3 +/- 0.4 ng of T (mean +/- SE) during the first 2 days in 13.6-fold by LH/FSH, 3.6-fold by Bu2cAMP, and 3-fold by PGF2alpha and PGE2- T was not detected in theca cultures after 2 days except in those treated with LH/FSH or Bu2cAMP, which produced 1.5 +/- 0.5 and 1.6 +/- 0.3 ng of T, respectively, at 4 days (mean +/- SE). These results suggest that under the present conditions, pieces of rabbit thecal tissue have a greater capacity to produce T de novo than do isolated granulosa cells, and indicate that T production is transiently stimulated by LH/FSH, Bu2cAMP, PGE2alpha, and PGE2."} {"id": "PMID:182456", "title": "Endometrial content of nuclear estrogen receptor and receptivity for ovoimplantation in the rat.", "content": "The purpose of this study was to provide information concerning the amount of nuclear binding sites for estrogen in endometrial cells during the first week of pregnancy in the rat. The \"insoluble\" (high-salt non-extractable) binding during the first four days of pregnancy follows a circadian rhythm, with a maximal value at midnight, and a minimal one a noon. By day 5, the amount plateaus at a minimal value. The number of estradiol binding sites of the soluble (high-salt extractable) nuclear fraction shows a similar pattern. All the necessary elements for the estrogen-dependent induction of endometrial receptivity for nidation appear, therefore, to be present already by day 3, but the turning on of the endometrial response to estrogen on day 4 seems to depend on additional factor(s).", "contents": "Endometrial content of nuclear estrogen receptor and receptivity for ovoimplantation in the rat. The purpose of this study was to provide information concerning the amount of nuclear binding sites for estrogen in endometrial cells during the first week of pregnancy in the rat. The \"insoluble\" (high-salt non-extractable) binding during the first four days of pregnancy follows a circadian rhythm, with a maximal value at midnight, and a minimal one a noon. By day 5, the amount plateaus at a minimal value. The number of estradiol binding sites of the soluble (high-salt extractable) nuclear fraction shows a similar pattern. All the necessary elements for the estrogen-dependent induction of endometrial receptivity for nidation appear, therefore, to be present already by day 3, but the turning on of the endometrial response to estrogen on day 4 seems to depend on additional factor(s)."} {"id": "PMID:182457", "title": "Changes in (125I) labeled human chorionic gonadotropin (hCG) binding to porcine granulosa cells during follicle development and cell culture.", "content": "The specific binding of (125I)iodo human chorionic gonadotropin to porcine granulosa cells isolated at two stages of follicle maturation was quantitated immediately after harvest and following 6-7 days of culture. Both porcine LH (pLH, LER 786-3) and hCG inhibited (125I)iodo hCG binding, while pFSH (ler-1132) did not compete for hCG with granulosa cells for 24-48 hours at 37 C did not alter its subsequent ability to bind to fresh cells. The binding of (125I)iodo hCG was a rapid process which was not readily reversible. Scatchard analysis of the equilibrium binding data resulted in linear plots showing the hCG binding capacity of highly differentiated (HD) cells, harvested from large preovulatory follicles, to be significantly greater than that of moderately differentiated (MD) cells isolated from smaller luteal phase follicles, both before (794 vs 93 pmoles/g; P less than 0.001) and after (157 vs 5 pmoles/g; P less than 0.001) culture. A decline in binding capacity occurred in both cell groups during culture and was associated with a significant decrease in progestin production. In contrast, the hCG binding affinity of the granulosa cell was equivalent at both stages of follicle development and remained unchanged after 6 days of culture (mean apparent Kd = 2.9 x 10-10M; n=27. These data indicate that porcine granulosa cells contain a homogeneous class of LH receptors whose number, but not affinity, increases during follicle maturation in vivo. The loss of receptors in vitro suggests the absence of some factors(s), as yet unidentified, critical to the maintenance and development of the receptor population.", "contents": "Changes in (125I) labeled human chorionic gonadotropin (hCG) binding to porcine granulosa cells during follicle development and cell culture. The specific binding of (125I)iodo human chorionic gonadotropin to porcine granulosa cells isolated at two stages of follicle maturation was quantitated immediately after harvest and following 6-7 days of culture. Both porcine LH (pLH, LER 786-3) and hCG inhibited (125I)iodo hCG binding, while pFSH (ler-1132) did not compete for hCG with granulosa cells for 24-48 hours at 37 C did not alter its subsequent ability to bind to fresh cells. The binding of (125I)iodo hCG was a rapid process which was not readily reversible. Scatchard analysis of the equilibrium binding data resulted in linear plots showing the hCG binding capacity of highly differentiated (HD) cells, harvested from large preovulatory follicles, to be significantly greater than that of moderately differentiated (MD) cells isolated from smaller luteal phase follicles, both before (794 vs 93 pmoles/g; P less than 0.001) and after (157 vs 5 pmoles/g; P less than 0.001) culture. A decline in binding capacity occurred in both cell groups during culture and was associated with a significant decrease in progestin production. In contrast, the hCG binding affinity of the granulosa cell was equivalent at both stages of follicle development and remained unchanged after 6 days of culture (mean apparent Kd = 2.9 x 10-10M; n=27. These data indicate that porcine granulosa cells contain a homogeneous class of LH receptors whose number, but not affinity, increases during follicle maturation in vivo. The loss of receptors in vitro suggests the absence of some factors(s), as yet unidentified, critical to the maintenance and development of the receptor population."} {"id": "PMID:182458", "title": "Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts.", "content": "Two metabolically distinct types of bone cell populations were isolated from mouse calvaria by a repetitive digestive procedure with a mixture of collagenase and trypsin. Cells released early in the digestion showed approximately two-fold increases in cAMP when treated with either parathormone or calcitonin. These populations were denoted CT type. Later eluting cells showed larger parathormone-induced increases in cAMP but did not respond to calcitonin. These populations were denoted PT type. Six metabolic and enzymatic activites were measured in the two types of populations: acid and alkaline phosphatases, hyaluronate synthesis, citrate decarboxylation, prolyl hydroxylase, and general protein synthesis. Although each of these activites was present in both cell types, the basal levels of acid phosphatase and hyaluronate synthesis were higher in the CT cells, whereas alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase were higher in te PT cells. Parathormone stimulated acid phosphatase and hyaluronate synthesis by 100-200% only in the CT cells; in inhibited alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase by 75-90% only in the PT cells. Calcitonin alone had no effect on any of these activities other than cAMP production, but in inhibited the action of parathormone in the CT cells. The sensitivities, time courses of development,and magnitudes of these hormonal effects were similar to those observed previously in intact calvaria, indicating that the isolated cell system is a reliable model for the study of bone metabolism. Based on the metabolic responses of the cells, we postulate that the CT type of populations is enriched in osteoclasts and, possibly, osteocytes, and the PT type of population is enriched in osteoblasts.", "contents": "Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts. Two metabolically distinct types of bone cell populations were isolated from mouse calvaria by a repetitive digestive procedure with a mixture of collagenase and trypsin. Cells released early in the digestion showed approximately two-fold increases in cAMP when treated with either parathormone or calcitonin. These populations were denoted CT type. Later eluting cells showed larger parathormone-induced increases in cAMP but did not respond to calcitonin. These populations were denoted PT type. Six metabolic and enzymatic activites were measured in the two types of populations: acid and alkaline phosphatases, hyaluronate synthesis, citrate decarboxylation, prolyl hydroxylase, and general protein synthesis. Although each of these activites was present in both cell types, the basal levels of acid phosphatase and hyaluronate synthesis were higher in the CT cells, whereas alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase were higher in te PT cells. Parathormone stimulated acid phosphatase and hyaluronate synthesis by 100-200% only in the CT cells; in inhibited alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase by 75-90% only in the PT cells. Calcitonin alone had no effect on any of these activities other than cAMP production, but in inhibited the action of parathormone in the CT cells. The sensitivities, time courses of development,and magnitudes of these hormonal effects were similar to those observed previously in intact calvaria, indicating that the isolated cell system is a reliable model for the study of bone metabolism. Based on the metabolic responses of the cells, we postulate that the CT type of populations is enriched in osteoclasts and, possibly, osteocytes, and the PT type of population is enriched in osteoblasts."} {"id": "PMID:182459", "title": "Effects of excess iodide and other anions on thyroid hormone secretion in normal or hypophysectomized rats treated with graded doses of thyroid hormone.", "content": "In order to obtain further information about the stimulatory action of excess iodide on thyroid hormone secretion in thyroxine (T4)-treated rats, experiments were performed in hypophysectomized rats, or rats treated with graded doses of T4 or triiodothyronine (T3).T3 as well as T4 played a permissive role in the production of the iodide effect in normal animals, but T3 was more effective than T4. Excess iodide stimulated thyroid hormone secretion in hypophysectomized animals, this finding being compatible with the hypothesis that, by inhibiting TSH secretion, T3 and T4 produced a condition in which excess iodide stimulated thyroid hormone secretion in intact rats. However, T4 played an additional role in thyroid hormone secretion by acting directly on the thyroid. In hypophysectomized animals, small doses of T4 stimulated thyroid hormone secretion, and this action was additive to that of excess iodide, whereas large doses of T4 were inhibitory and reduced the effectiveness of excess iodide. The stimulatory action on thyroid hormone secretion was specific for iodide and was not shared by other anions. The action of excess iodide was blocked by methimazole. We suggest that excess iodide stimulates thyroid hormone secretion by increasing intrathyroidal concentrations of cyclic AMP in the absence of TSH, and that this increase in cyclic AMP concentration is blocked by methimazole.", "contents": "Effects of excess iodide and other anions on thyroid hormone secretion in normal or hypophysectomized rats treated with graded doses of thyroid hormone. In order to obtain further information about the stimulatory action of excess iodide on thyroid hormone secretion in thyroxine (T4)-treated rats, experiments were performed in hypophysectomized rats, or rats treated with graded doses of T4 or triiodothyronine (T3).T3 as well as T4 played a permissive role in the production of the iodide effect in normal animals, but T3 was more effective than T4. Excess iodide stimulated thyroid hormone secretion in hypophysectomized animals, this finding being compatible with the hypothesis that, by inhibiting TSH secretion, T3 and T4 produced a condition in which excess iodide stimulated thyroid hormone secretion in intact rats. However, T4 played an additional role in thyroid hormone secretion by acting directly on the thyroid. In hypophysectomized animals, small doses of T4 stimulated thyroid hormone secretion, and this action was additive to that of excess iodide, whereas large doses of T4 were inhibitory and reduced the effectiveness of excess iodide. The stimulatory action on thyroid hormone secretion was specific for iodide and was not shared by other anions. The action of excess iodide was blocked by methimazole. We suggest that excess iodide stimulates thyroid hormone secretion by increasing intrathyroidal concentrations of cyclic AMP in the absence of TSH, and that this increase in cyclic AMP concentration is blocked by methimazole."} {"id": "PMID:182460", "title": "A cytoplasmic estradiol receptor in rat testicular tissue.", "content": "Testicular cytosol from Sprague-Dawley rats was shown to possess an estradiol binding component which exhibited the properties of a receptor. Specific binding of estradiol by the receptor was shown, at 4C in vitro, to reach equilibrium by 6 h. That level of binding was maintained at a plateau for 18 h. Estradiol binding was demonstrated to increase linearly as a function of testicular cytosol concentration ultilized. The Ka at equilibrium was determined as 4.07 .05 x 1010M-1, while the number of binding sites for whole testicular tissue from mature rats was 1.16 x 10-14 +/- 0.061 moles/mg cytosol protein. Sucrose gradient sedimentation analysis of the cytosol receptor revealed that the major peak of radioactivity migrated in the 8S region. Enzymatic treatment of the cytosol demonstrated that the binding component was protein in nature. Heat treatment, 70 C for 10 min, resulted in 83% loss of the receptor activity. Storage in liquid N2 (for as long as 60 days) was shown to maintain receptor activity. Steroid specificity studies revealed that other estrogens were competitive with 17beta-estradiol for binding sites, but progestins, testosterone, and dihydrotestosterone did not affect estradiol binding. Tissue specificity studies showed that the capacity of testicular cytosol to bind estradiol was much greater than that of several non-target organs. Ontogenically, the cytoplasmic estradiol-binding capacity/testis was low from 7 to 21 days of age, but rose dramatically between 3 and 7 weeks of age, and an apparent plateau was reached at 15 weeks. The injection of unlabeled 17beta-estradiolin vvio was shown to deplete the cytosol of estradiol binding sites as determined in vitro. Depletion was rapid, occurring within 30 min, and the cytoplasmic estradiol receptors remained low for a period of 4 h. At 6 h, replenishment has occurred and control levels of cytoplasmic receptors were restored by 12 h. These results suggest that an estradiol receptor is present in testicular tissue of the rat, and that binding capacity is maximum in the mature testis.", "contents": "A cytoplasmic estradiol receptor in rat testicular tissue. Testicular cytosol from Sprague-Dawley rats was shown to possess an estradiol binding component which exhibited the properties of a receptor. Specific binding of estradiol by the receptor was shown, at 4C in vitro, to reach equilibrium by 6 h. That level of binding was maintained at a plateau for 18 h. Estradiol binding was demonstrated to increase linearly as a function of testicular cytosol concentration ultilized. The Ka at equilibrium was determined as 4.07 .05 x 1010M-1, while the number of binding sites for whole testicular tissue from mature rats was 1.16 x 10-14 +/- 0.061 moles/mg cytosol protein. Sucrose gradient sedimentation analysis of the cytosol receptor revealed that the major peak of radioactivity migrated in the 8S region. Enzymatic treatment of the cytosol demonstrated that the binding component was protein in nature. Heat treatment, 70 C for 10 min, resulted in 83% loss of the receptor activity. Storage in liquid N2 (for as long as 60 days) was shown to maintain receptor activity. Steroid specificity studies revealed that other estrogens were competitive with 17beta-estradiol for binding sites, but progestins, testosterone, and dihydrotestosterone did not affect estradiol binding. Tissue specificity studies showed that the capacity of testicular cytosol to bind estradiol was much greater than that of several non-target organs. Ontogenically, the cytoplasmic estradiol-binding capacity/testis was low from 7 to 21 days of age, but rose dramatically between 3 and 7 weeks of age, and an apparent plateau was reached at 15 weeks. The injection of unlabeled 17beta-estradiolin vvio was shown to deplete the cytosol of estradiol binding sites as determined in vitro. Depletion was rapid, occurring within 30 min, and the cytoplasmic estradiol receptors remained low for a period of 4 h. At 6 h, replenishment has occurred and control levels of cytoplasmic receptors were restored by 12 h. These results suggest that an estradiol receptor is present in testicular tissue of the rat, and that binding capacity is maximum in the mature testis."} {"id": "PMID:182461", "title": "Further characterization of a rat ovarian testosterone receptor with evidence for nuclear translocation.", "content": "We have recently described receptor like testosterone (T)-binding protein in the cytosol of ovaries from estrogen-primed hypophysectomized immature female rats (HIFR). This binding protein is thermolabile, saturable, specific for T, and sediments at 7-8 S on sucrose gradients. We now report the further characterization of this protein. It is present in the cytosol of isolated granulosa cells, has a molecular weight of 240,000, a frictional ratio of 1.8, and a mean Stokes radius of 73 A. The binding protein is acidic and cysteine residues are necessary for binding. We have also demonstrated the selective nuclear accumulation of T by granulosa cells after the in vivo administration of (3H)T to estrogen primed HIFR. After the in vitro incubation of the ovaries with (3H)T, a thermolabile protein specific for T was extracted from nuclei under high-salt conditions. The cytosol and nuclear T-binding proteins described in this report have many characteristics of an androgen receptor, and may play a role in the regulation of granulosa cell proliferation during preantral follicular growth.", "contents": "Further characterization of a rat ovarian testosterone receptor with evidence for nuclear translocation. We have recently described receptor like testosterone (T)-binding protein in the cytosol of ovaries from estrogen-primed hypophysectomized immature female rats (HIFR). This binding protein is thermolabile, saturable, specific for T, and sediments at 7-8 S on sucrose gradients. We now report the further characterization of this protein. It is present in the cytosol of isolated granulosa cells, has a molecular weight of 240,000, a frictional ratio of 1.8, and a mean Stokes radius of 73 A. The binding protein is acidic and cysteine residues are necessary for binding. We have also demonstrated the selective nuclear accumulation of T by granulosa cells after the in vivo administration of (3H)T to estrogen primed HIFR. After the in vitro incubation of the ovaries with (3H)T, a thermolabile protein specific for T was extracted from nuclei under high-salt conditions. The cytosol and nuclear T-binding proteins described in this report have many characteristics of an androgen receptor, and may play a role in the regulation of granulosa cell proliferation during preantral follicular growth."} {"id": "PMID:182462", "title": "Hormonal stimulation of alpha-amylase synthesis in porcine pancreatic minces.", "content": "Minces of porcine pancreas maintained a linear rate or protein synthesis for more than 4 h with similar kinetics in the presence of absence of hormones. alpha-Amylase protein, quantitated by using glycogen percipitation, SDS polyacrylamide gel analysis, and radioimmunoassay, was found to represent 6-7% of the total protein content of the minces. The addition of prostaglandin E1 (10-7M), or a pancreozymin preparation (3-10 Crick-Harper-Raper units/ml) to the incubation media produced within 60 min an increase in alpha-amylase protein above that stored in the tissue 10- to 20-fold greater than that observed in control minces. The addiction of cAMP analogs (10(-3)M) to the medium produced a more variable stimulation of alpha-amylase content. Quantitation of the incorporation of radiolabeled amino acid into alpha-amylase protein with simultaneous determination of the specific activity of the precursor pool suggested that these agents produced at least 3- to 5-fold stimulation of de novo alpha-amylase synthesis. This stimulation was not the result of decreased rates of alpha-amylase catabolism. The addition of actinomycin D (20 mug/ml), a concentration inhibiting more than 93% of new RNA synthesis, failed to alter the stimulation of alpha-amylase synthesis by these agents. Apparent hormonal stimulation of non-alpha-amylase protein synthesis was also observed.", "contents": "Hormonal stimulation of alpha-amylase synthesis in porcine pancreatic minces. Minces of porcine pancreas maintained a linear rate or protein synthesis for more than 4 h with similar kinetics in the presence of absence of hormones. alpha-Amylase protein, quantitated by using glycogen percipitation, SDS polyacrylamide gel analysis, and radioimmunoassay, was found to represent 6-7% of the total protein content of the minces. The addition of prostaglandin E1 (10-7M), or a pancreozymin preparation (3-10 Crick-Harper-Raper units/ml) to the incubation media produced within 60 min an increase in alpha-amylase protein above that stored in the tissue 10- to 20-fold greater than that observed in control minces. The addiction of cAMP analogs (10(-3)M) to the medium produced a more variable stimulation of alpha-amylase content. Quantitation of the incorporation of radiolabeled amino acid into alpha-amylase protein with simultaneous determination of the specific activity of the precursor pool suggested that these agents produced at least 3- to 5-fold stimulation of de novo alpha-amylase synthesis. This stimulation was not the result of decreased rates of alpha-amylase catabolism. The addition of actinomycin D (20 mug/ml), a concentration inhibiting more than 93% of new RNA synthesis, failed to alter the stimulation of alpha-amylase synthesis by these agents. Apparent hormonal stimulation of non-alpha-amylase protein synthesis was also observed."} {"id": "PMID:182463", "title": "16Beta-hydroxydehydroepiandrosterone: the dichotomy between renal receptor binding and urinary electrolyte activity.", "content": "Excessive production of 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA) has been suggested as a cause of low-renin essential hypertension. The mineralocorticoid effect of 16beta-OH-DHEA was reported to be one-fortieth that of aldostereone in the rat bioassay. Using kidney slices from adrenalectomized rats, the affinity of 16beta-OH-DHEA and a series of related compounds for mineralocorticoid receptors has been determined. In studies done at both 4 C and 37 C, the affinity of 16beta-OHDHEA for mineralocorticoid receptors was found to be less than 0.1% that of aldosterone (P less than 0.01). Various related steroids and/or potential metabolites similarly showed negligible affinity for the aldosterone receptor. In addition, In addition, 16beta-OHDHEA showed no significant affinity for renal dexamethasone-binding sites (Type II glucocorticoid receptors), corticosterone-binding sites (Type III glucocorticoid receptors), dihydrotestosterone binding sites, or estradiol binding sites. In in vivo competition experiments, the concurrent administration of 50 mug deoxycorticosterone reduced (3H)aldosterone binding to 20-30% of control levels; 50 mug 16beta-OH-DHEA did not compete for (3H)aldosterone binding sites. In in vivo bioassay electrolyte excretion was found-in contrast to that of aldosterone-to be variable. Within a given group, certain rats reproducibly responded to 16beta-OH-DHEA by sodium retention and kaliuresis; in others no response was observed. In vitro binding studies comparing \"responders\" with \"non-responders\" demonstrated that in neither group did 16beta-OH-DHEA have significant affinity for renal mineralocorticoid receptors. Accordingly, the mechanism whereby 16beta-OHDHEA produces changes in urinary electrolyte excretion appears independent of classical mineralocorticoid effector mechanisms. The conditions under which this effect is seen await eludication.", "contents": "16Beta-hydroxydehydroepiandrosterone: the dichotomy between renal receptor binding and urinary electrolyte activity. Excessive production of 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA) has been suggested as a cause of low-renin essential hypertension. The mineralocorticoid effect of 16beta-OH-DHEA was reported to be one-fortieth that of aldostereone in the rat bioassay. Using kidney slices from adrenalectomized rats, the affinity of 16beta-OH-DHEA and a series of related compounds for mineralocorticoid receptors has been determined. In studies done at both 4 C and 37 C, the affinity of 16beta-OHDHEA for mineralocorticoid receptors was found to be less than 0.1% that of aldosterone (P less than 0.01). Various related steroids and/or potential metabolites similarly showed negligible affinity for the aldosterone receptor. In addition, In addition, 16beta-OHDHEA showed no significant affinity for renal dexamethasone-binding sites (Type II glucocorticoid receptors), corticosterone-binding sites (Type III glucocorticoid receptors), dihydrotestosterone binding sites, or estradiol binding sites. In in vivo competition experiments, the concurrent administration of 50 mug deoxycorticosterone reduced (3H)aldosterone binding to 20-30% of control levels; 50 mug 16beta-OH-DHEA did not compete for (3H)aldosterone binding sites. In in vivo bioassay electrolyte excretion was found-in contrast to that of aldosterone-to be variable. Within a given group, certain rats reproducibly responded to 16beta-OH-DHEA by sodium retention and kaliuresis; in others no response was observed. In vitro binding studies comparing \"responders\" with \"non-responders\" demonstrated that in neither group did 16beta-OH-DHEA have significant affinity for renal mineralocorticoid receptors. Accordingly, the mechanism whereby 16beta-OHDHEA produces changes in urinary electrolyte excretion appears independent of classical mineralocorticoid effector mechanisms. The conditions under which this effect is seen await eludication."} {"id": "PMID:182464", "title": "Gastrin in the perinatal rat pancreas and gastric antrum: immunofluorescence localization of pancreatic gastrin cells and gastrin secretion in monolayer cell cultures.", "content": "The presence and development of immunoreactive gastrin (IRGa) in the fetal and neonatal pancreas and pyloric antrum of the rat were studied. IRGa appeared in both organs at least as early as the 16th day of fetal life. Antral IRGa increased rapidly and continuously in the neonatal period, while pancreatic IRGa concentration increased and was maintained at a relatively constant level from days 5 to 35. Monolayer cell cultures of the neonatal rat pancreas were used to evaluate the role of cyclic AMP mediated release of gastrin. The addition of N6,O2'-dibutyryl cyclic AMP (4 mM) or theophylline (4 mM) to the culture medium induced significant release of gastrin. The stimulation of adenylate cyclase with cholera toxin (10 ng/ml) also resulted in significant gastrin release. Long-term cultures (18-24 days) were shown to release gastrin continuously at a relatively constant rate. The cellular localization of pancreatic gastrin in 7-day-old cultures was performed by immunological techniques, using fluorescein-labeled antibodies to gastrin. The gastrin-containing cells were located at the periphery of most of the endocrine cell clusters. Immunofluorescence techniques for insulin and glucagon also showed that the alpha cells had a similar peripheral distribution, although they were more frequent in number. In contrast, insulin-containing cells were numerous and were present in all areas of the endocrine cell clusters. The studies support the following conclusions: a) Gastrin is present in the rat pancreas, even as early as late fetal life; b) Gastrin-producing cells are present and functionally competent in monolayer cell cultures of the neonatal rat pancreas for prolonged periods of time (24 days); c) Gastrin is released from these cells when intracellular levels of cyclic AMP are increased; d) By immunofluorescence methods, the gastrin-producing cells in pancreatic cell cultures are found to be located at the periphery of the endocrine cell clusters.", "contents": "Gastrin in the perinatal rat pancreas and gastric antrum: immunofluorescence localization of pancreatic gastrin cells and gastrin secretion in monolayer cell cultures. The presence and development of immunoreactive gastrin (IRGa) in the fetal and neonatal pancreas and pyloric antrum of the rat were studied. IRGa appeared in both organs at least as early as the 16th day of fetal life. Antral IRGa increased rapidly and continuously in the neonatal period, while pancreatic IRGa concentration increased and was maintained at a relatively constant level from days 5 to 35. Monolayer cell cultures of the neonatal rat pancreas were used to evaluate the role of cyclic AMP mediated release of gastrin. The addition of N6,O2'-dibutyryl cyclic AMP (4 mM) or theophylline (4 mM) to the culture medium induced significant release of gastrin. The stimulation of adenylate cyclase with cholera toxin (10 ng/ml) also resulted in significant gastrin release. Long-term cultures (18-24 days) were shown to release gastrin continuously at a relatively constant rate. The cellular localization of pancreatic gastrin in 7-day-old cultures was performed by immunological techniques, using fluorescein-labeled antibodies to gastrin. The gastrin-containing cells were located at the periphery of most of the endocrine cell clusters. Immunofluorescence techniques for insulin and glucagon also showed that the alpha cells had a similar peripheral distribution, although they were more frequent in number. In contrast, insulin-containing cells were numerous and were present in all areas of the endocrine cell clusters. The studies support the following conclusions: a) Gastrin is present in the rat pancreas, even as early as late fetal life; b) Gastrin-producing cells are present and functionally competent in monolayer cell cultures of the neonatal rat pancreas for prolonged periods of time (24 days); c) Gastrin is released from these cells when intracellular levels of cyclic AMP are increased; d) By immunofluorescence methods, the gastrin-producing cells in pancreatic cell cultures are found to be located at the periphery of the endocrine cell clusters."} {"id": "PMID:182465", "title": "A high-affinity estrogen-binding protein in rat placental trophoblast.", "content": "A high-affinity, low-capacity estradiol-binding molecule (RE) has been demonstrated in the basal zone trophoblast (BZT) of the pregnant rat. On day 11 of pregnancy (day 0 = first sperm-positive day) RE is present in BZT cytosol, where it has a ka of 1.2 X 10(6)M-1 sec-1, t1/2 = 12.7 min, at 20 C. The Kd, under similar conditions, consists of 2 components, 1.3 X 10(-4) sec-1, t1/2 = 90 min, and 5.9 X 10(-5) sec-1, t1/2 = 196 min. When one uses the faster component, the equilibrium constant, Kd, obtained from kd/ka is 1.1 X 10(-10)M, in close agreement with that obtained from Scatchard analysis of specific estradiol (E2) binding at 20 C. On day 11 there were approximately 12,000 sites/cell in BZT cytosol. Scatchard analysis of nuclear RE on day 11 indicated a Kd of 1.85 X 10(-10)M and approximately 21,000 sites/nucleus, but, in day 15 BZT, nuclear RE was undetectable. Neither cytosol nor nuclei prepared from placental labyrinthine zone (LZT) tissue (fetal placenta) showed evidence of high-affinity, low-capacity E2 binding. Sucrose density gradient analysis on 5-20% linear gradients showed the cytosol RE to be approximately 4S whether in high or low-salt conditions. When measured against binding by 3H-labeled estradiol (*E2), the cytosol BTZ RE was competed for strongly (80-90%) by estrone, estriol, diethylstilbestrol, and estradiol-17alpha at 200 times excess. Nafoxidine-HCl, also at 200X excess, competed to approximately 50%. Corticosterone, progesterone, testosterone, dehydroepiandrosterone, and pregnenolone did not compete. The hormone specificity of nuclear BZT RE was similar to that of the comparable cytosol RE with the exception that nafoxidine did not compete. This was probably due to differences in kinetics, nafoxidine requiring a longer time to reach equilibrium than the other estrogens. The size of the nuclear RE by sucrose density gradient analysis was approximately 2S by KCl extraction (which was inefficient) or 4S by trypsin extraction. We conclude that the BZT of the day-11 rat placenta contains an estrogen-binding molecule with many of the attributes of a true receptor.", "contents": "A high-affinity estrogen-binding protein in rat placental trophoblast. A high-affinity, low-capacity estradiol-binding molecule (RE) has been demonstrated in the basal zone trophoblast (BZT) of the pregnant rat. On day 11 of pregnancy (day 0 = first sperm-positive day) RE is present in BZT cytosol, where it has a ka of 1.2 X 10(6)M-1 sec-1, t1/2 = 12.7 min, at 20 C. The Kd, under similar conditions, consists of 2 components, 1.3 X 10(-4) sec-1, t1/2 = 90 min, and 5.9 X 10(-5) sec-1, t1/2 = 196 min. When one uses the faster component, the equilibrium constant, Kd, obtained from kd/ka is 1.1 X 10(-10)M, in close agreement with that obtained from Scatchard analysis of specific estradiol (E2) binding at 20 C. On day 11 there were approximately 12,000 sites/cell in BZT cytosol. Scatchard analysis of nuclear RE on day 11 indicated a Kd of 1.85 X 10(-10)M and approximately 21,000 sites/nucleus, but, in day 15 BZT, nuclear RE was undetectable. Neither cytosol nor nuclei prepared from placental labyrinthine zone (LZT) tissue (fetal placenta) showed evidence of high-affinity, low-capacity E2 binding. Sucrose density gradient analysis on 5-20% linear gradients showed the cytosol RE to be approximately 4S whether in high or low-salt conditions. When measured against binding by 3H-labeled estradiol (*E2), the cytosol BTZ RE was competed for strongly (80-90%) by estrone, estriol, diethylstilbestrol, and estradiol-17alpha at 200 times excess. Nafoxidine-HCl, also at 200X excess, competed to approximately 50%. Corticosterone, progesterone, testosterone, dehydroepiandrosterone, and pregnenolone did not compete. The hormone specificity of nuclear BZT RE was similar to that of the comparable cytosol RE with the exception that nafoxidine did not compete. This was probably due to differences in kinetics, nafoxidine requiring a longer time to reach equilibrium than the other estrogens. The size of the nuclear RE by sucrose density gradient analysis was approximately 2S by KCl extraction (which was inefficient) or 4S by trypsin extraction. We conclude that the BZT of the day-11 rat placenta contains an estrogen-binding molecule with many of the attributes of a true receptor."} {"id": "PMID:182466", "title": "Induction of follicle-stimulating hormone (FSH) receptors in rat ovaries by estrogen priming.", "content": "Estrogen pretreatment of hypophysectomized immature rats stimulated granulosa cell proliferation and enhanced FSH binding to the ovary in vivo. The present studies were undertaken to ascertain whether estrogen pretreatment altered the number of specific FSH receptor sites per ovarian cell, resulting in increased FSH binding. Cell suspensions were prepared from the ovaries of groups of rats pretreated with graded doses of 17beta-estradiol. The isolated cells contained specific FSH receptors with high affinity for FSH. The results of these studies clearly showed that the number of specific FSH receptors per ovarian cell was unaffected by pretreatment with graded doses of 17beta-estradiol or with diethylstilbestrol. The enhanced in vivo FSH binding was solely the result of estrogen-induced proliferation of granulosa cells with a fixed number of specific FSH receptors per cell.", "contents": "Induction of follicle-stimulating hormone (FSH) receptors in rat ovaries by estrogen priming. Estrogen pretreatment of hypophysectomized immature rats stimulated granulosa cell proliferation and enhanced FSH binding to the ovary in vivo. The present studies were undertaken to ascertain whether estrogen pretreatment altered the number of specific FSH receptor sites per ovarian cell, resulting in increased FSH binding. Cell suspensions were prepared from the ovaries of groups of rats pretreated with graded doses of 17beta-estradiol. The isolated cells contained specific FSH receptors with high affinity for FSH. The results of these studies clearly showed that the number of specific FSH receptors per ovarian cell was unaffected by pretreatment with graded doses of 17beta-estradiol or with diethylstilbestrol. The enhanced in vivo FSH binding was solely the result of estrogen-induced proliferation of granulosa cells with a fixed number of specific FSH receptors per cell."} {"id": "PMID:182467", "title": "Lactogenic and growth hormone-like activities in pregnancy determined by radioreceptor assays.", "content": "Factors with growth hormone and lactogenic activities have been identified in serum samples and placental extracts of 9 species using a radioreceptor assay for prolactin or lactogens (RRA-PRL) and one for growth hormone-like activity (RRA-GH). The concentrations of placental lactogen (PL) and growth hormone-like activity (GHLA) in pregnancy were different in each species. The levels of PL began to rise at or before mid-pregnancy and either remained elevated until term (hamster, goat, sheep, monkey, and human), declined gradually after reaching peak concentrations just beyond mid-pregnancy (guinea pig), or had 2 peaks of activity (mouse, rat). The peak concentrations in different species ranged from 350 ng/ml in the cow to 45,000 ng/ml in monkey serum samples. The concentrations of GHLA were similar to PL levels in the guinea pig, goat, cow, and monkey but were lower than PL levels in the sheep and human. The maximal concentrations of PL and GHLA in placental extracts varied from 1 mug/g in guinea pigs to 200 mug/g in sheep. The ratio of lactogenic/growth hormone-like activity of both serum and placental extracts varied greatly among the various species. Gel filtration studies of serum samples revealed that PL and GHLA in the hamster, mouse and rat had different elution volumes, whereas, in the remaining species, the two activities co-eluted.", "contents": "Lactogenic and growth hormone-like activities in pregnancy determined by radioreceptor assays. Factors with growth hormone and lactogenic activities have been identified in serum samples and placental extracts of 9 species using a radioreceptor assay for prolactin or lactogens (RRA-PRL) and one for growth hormone-like activity (RRA-GH). The concentrations of placental lactogen (PL) and growth hormone-like activity (GHLA) in pregnancy were different in each species. The levels of PL began to rise at or before mid-pregnancy and either remained elevated until term (hamster, goat, sheep, monkey, and human), declined gradually after reaching peak concentrations just beyond mid-pregnancy (guinea pig), or had 2 peaks of activity (mouse, rat). The peak concentrations in different species ranged from 350 ng/ml in the cow to 45,000 ng/ml in monkey serum samples. The concentrations of GHLA were similar to PL levels in the guinea pig, goat, cow, and monkey but were lower than PL levels in the sheep and human. The maximal concentrations of PL and GHLA in placental extracts varied from 1 mug/g in guinea pigs to 200 mug/g in sheep. The ratio of lactogenic/growth hormone-like activity of both serum and placental extracts varied greatly among the various species. Gel filtration studies of serum samples revealed that PL and GHLA in the hamster, mouse and rat had different elution volumes, whereas, in the remaining species, the two activities co-eluted."} {"id": "PMID:182468", "title": "Effects of vitamin D and its metabolites on calcium transport in the diabetic rat.", "content": "We studied diabetic rats, 5 days after streptozotocin injection, and matched controls to determine whether depressed duodenal calcium absorption associated with uncontrolled diabetes in the rat would respond to vitamin D or its metabolites. At the appropriate time following the intravenous injection of 0.25 mug of either vitamin D3, 25-hydroxycholecalciferol (25-OHD3), 1,25-dihydroxycholecalciferol (1,25-OH)2D3), or 1alpha-hydroxycholecalciferol (1alpha-OHD3) to half of each diabetic and control group, calcium transport was evaluated using everted duodenal sacs with 0.4 mM40Ca and tracer 45Ca on both mucosal and serosal surfaces. All agents stimulated duodenal calcium absorption in controls. Diabetics responded only to 1,25-(OH)2D3, the metabolite that acts directly on the duodenum, and to its synthetic analog, 1alpha-OHD3. 1alpha-OHD3 is activated to 1,25-(OH)2D3 by 25-hydroxylation in the liver; 25-OHD3 must be 1alpha-hydroxylated in the kidney to be active. The stimulation of duodenal calcium absorption in diabetic rats by 1alpha-OHD3, but not by either vitamin D3 or 25-OHD3, is most consistent with a defect in vitamin D metabolism at the 1alpha-hydroxylation step in the kidney.", "contents": "Effects of vitamin D and its metabolites on calcium transport in the diabetic rat. We studied diabetic rats, 5 days after streptozotocin injection, and matched controls to determine whether depressed duodenal calcium absorption associated with uncontrolled diabetes in the rat would respond to vitamin D or its metabolites. At the appropriate time following the intravenous injection of 0.25 mug of either vitamin D3, 25-hydroxycholecalciferol (25-OHD3), 1,25-dihydroxycholecalciferol (1,25-OH)2D3), or 1alpha-hydroxycholecalciferol (1alpha-OHD3) to half of each diabetic and control group, calcium transport was evaluated using everted duodenal sacs with 0.4 mM40Ca and tracer 45Ca on both mucosal and serosal surfaces. All agents stimulated duodenal calcium absorption in controls. Diabetics responded only to 1,25-(OH)2D3, the metabolite that acts directly on the duodenum, and to its synthetic analog, 1alpha-OHD3. 1alpha-OHD3 is activated to 1,25-(OH)2D3 by 25-hydroxylation in the liver; 25-OHD3 must be 1alpha-hydroxylated in the kidney to be active. The stimulation of duodenal calcium absorption in diabetic rats by 1alpha-OHD3, but not by either vitamin D3 or 25-OHD3, is most consistent with a defect in vitamin D metabolism at the 1alpha-hydroxylation step in the kidney."} {"id": "PMID:182469", "title": "Concerning the hormonal regulation of androgen binding protein in rat testis.", "content": "Androgen binding protein (ABP) was measured in testis following an acute injection of FSH to ascertain whether this protein could serve as an endpoint marker of FSH action in the Sertoli cell. A single intravenous injection of oFSH (200 mug NIH-S-10) resulted in a rapid stimulation of ABP activity in testis of either 10- or 14-day old rats. Maximal increases were noted by 2 h in both cases (undetectable to 0.9, and 0.3 to 1.5 pmol ABP/mg protein in 10- and 14-day old rats, respectively) and by 4h ABP activity had again returned to control values. Although FSH failed to acutely stimulate ABP in 60-day-old rats, hypophysectomy of these animals resulted in a return of sensitivity within 3 days. The acute stimulation of ABP by FSH was also shown to be dependent upon both the route of hormone administration and the dose of FSH. Finally, the rapid decrease in ABP activity following FSH could be prevented by injection of a second dose of hormone. ABP activity was also increased by intratesticular injection of an analog of cyclic AMP, 8-bromo cAMP. This response was also dose-dependent and the time course of response was indistinguishable from that resulting following FSH. A test of nucleotide specificity revealed that any adenine nucleotide would stimulate ABP, whereas guanine compounds were ineffective. Peptide hormone specificity was next examined. It was determined that 200 mug of a variety of crude pituitary hormone preparations (LH, GH, PRL and ACTH) were stimulatory. However, when highly purified hormones were utilized, hFSH (LER-1577) did not increase testicular ABP whereas 1 mug of oLH (Papkoff) was maximally stimulatory. Further studies revealed that all compounds (including peptide hormones and nucleotides) which resulted in acute elevation of ABP activity also increased the intratesticular concentration of testosterone. Moreover, a single ip injection of testosterone produced a steroid specific stimulation of ABP which reached maximal levels within 1 h. These findings suggest that the acute regulation of ABP activity in the testis may be a result of the intratesticular concentration of testosterone and not due to a direct effect of FSH as had been previously hypothesized.", "contents": "Concerning the hormonal regulation of androgen binding protein in rat testis. Androgen binding protein (ABP) was measured in testis following an acute injection of FSH to ascertain whether this protein could serve as an endpoint marker of FSH action in the Sertoli cell. A single intravenous injection of oFSH (200 mug NIH-S-10) resulted in a rapid stimulation of ABP activity in testis of either 10- or 14-day old rats. Maximal increases were noted by 2 h in both cases (undetectable to 0.9, and 0.3 to 1.5 pmol ABP/mg protein in 10- and 14-day old rats, respectively) and by 4h ABP activity had again returned to control values. Although FSH failed to acutely stimulate ABP in 60-day-old rats, hypophysectomy of these animals resulted in a return of sensitivity within 3 days. The acute stimulation of ABP by FSH was also shown to be dependent upon both the route of hormone administration and the dose of FSH. Finally, the rapid decrease in ABP activity following FSH could be prevented by injection of a second dose of hormone. ABP activity was also increased by intratesticular injection of an analog of cyclic AMP, 8-bromo cAMP. This response was also dose-dependent and the time course of response was indistinguishable from that resulting following FSH. A test of nucleotide specificity revealed that any adenine nucleotide would stimulate ABP, whereas guanine compounds were ineffective. Peptide hormone specificity was next examined. It was determined that 200 mug of a variety of crude pituitary hormone preparations (LH, GH, PRL and ACTH) were stimulatory. However, when highly purified hormones were utilized, hFSH (LER-1577) did not increase testicular ABP whereas 1 mug of oLH (Papkoff) was maximally stimulatory. Further studies revealed that all compounds (including peptide hormones and nucleotides) which resulted in acute elevation of ABP activity also increased the intratesticular concentration of testosterone. Moreover, a single ip injection of testosterone produced a steroid specific stimulation of ABP which reached maximal levels within 1 h. These findings suggest that the acute regulation of ABP activity in the testis may be a result of the intratesticular concentration of testosterone and not due to a direct effect of FSH as had been previously hypothesized."} {"id": "PMID:182470", "title": "Reductions in glucocorticoid inhibition of glucose oxidation and presumptive glucocorticoid receptor content in rat adipocytes during aging.", "content": "Exposure of adipocytes to glucocorticoid hormones in vitro causes inhibition of glucose transport and metabolsim. Maximal inhibition of glucose oxidations is reduced from 42-50 to 22-25 to 5-8% in young, mature, and senescent rat adipocytes, respectively. Percent values also reflect absolute reductions since basal levels of glucose oxidation per cell are constant at all ages. Adipocytes of CD strain rats continue to increase in size throughout their lifespan, while cell size remains constant during the latter 80% of the Wistar adipocyte lifespan. Thus, cellular age, as well as possibly size, seems to be associated with these changes since they occur in adipocytes of both strains. Concentrations as well as absolute numbers of presumptive glucocorticoid receptors per cell are progressively reduced during maturation and aging of adipocytes in both rat strains. Glucocorticoid effects are known to require about 2 h and can be blocked by various antimetabolites during this period, reminiscent of classical steroid receptor-mediated responses. Thus, gradual loss of glucocorticoid receptors from adipocytes during maturation and aging may be related to progressively decreased glucocorticoid responsiveness.", "contents": "Reductions in glucocorticoid inhibition of glucose oxidation and presumptive glucocorticoid receptor content in rat adipocytes during aging. Exposure of adipocytes to glucocorticoid hormones in vitro causes inhibition of glucose transport and metabolsim. Maximal inhibition of glucose oxidations is reduced from 42-50 to 22-25 to 5-8% in young, mature, and senescent rat adipocytes, respectively. Percent values also reflect absolute reductions since basal levels of glucose oxidation per cell are constant at all ages. Adipocytes of CD strain rats continue to increase in size throughout their lifespan, while cell size remains constant during the latter 80% of the Wistar adipocyte lifespan. Thus, cellular age, as well as possibly size, seems to be associated with these changes since they occur in adipocytes of both strains. Concentrations as well as absolute numbers of presumptive glucocorticoid receptors per cell are progressively reduced during maturation and aging of adipocytes in both rat strains. Glucocorticoid effects are known to require about 2 h and can be blocked by various antimetabolites during this period, reminiscent of classical steroid receptor-mediated responses. Thus, gradual loss of glucocorticoid receptors from adipocytes during maturation and aging may be related to progressively decreased glucocorticoid responsiveness."} {"id": "PMID:182471", "title": "Distribution binding sites for the progesterone receptor within chick oviduct chromatin.", "content": "Chromatin from the oviducts of estrogen-treated chicks was sheared and fractionated on sucrose gradients. This resulted in the production of several chromatin fractions which differ in their sedimentation properties, protein composition, the number of acceptor sites for the progesterone-receptor complex, and the ability to serve as a template for RNA synthesis. The pellet chromatin fraction shows an enhanced ability to bind the progesterone-receptor complex in vitro and in cell-free systems. Kinetic analysis indicates that the majority of the acceptor sites for the progesterone-receptor complex are located in the pellet chromatin fraction which is lowest in template activity. The sites may be important loci for initiating the changes in RNA synthesis following the exposure of target cells to steroid hormones.", "contents": "Distribution binding sites for the progesterone receptor within chick oviduct chromatin. Chromatin from the oviducts of estrogen-treated chicks was sheared and fractionated on sucrose gradients. This resulted in the production of several chromatin fractions which differ in their sedimentation properties, protein composition, the number of acceptor sites for the progesterone-receptor complex, and the ability to serve as a template for RNA synthesis. The pellet chromatin fraction shows an enhanced ability to bind the progesterone-receptor complex in vitro and in cell-free systems. Kinetic analysis indicates that the majority of the acceptor sites for the progesterone-receptor complex are located in the pellet chromatin fraction which is lowest in template activity. The sites may be important loci for initiating the changes in RNA synthesis following the exposure of target cells to steroid hormones."} {"id": "PMID:182472", "title": "Adenosine-mediated stimulation of bone cell adenylate cyclase activity.", "content": "Adenosine rapidly stimulated adenylate cyclase activity but did not modify cyclic AMP degradation when added to a particulate fraction prepared from isolated bone cells. The effect of adenosine was one-half maximal at 5-10 micronM, and was not mimicked by 5' AMP, inosine, guanosine, uridine, adenine, or ribose. Basal and adenosine-stimulated adenylate cyclase activites were directly proportional to the concentration of particulate protein in the assay system. Theophylline decreased the degree to which adenosine stimulated adenylate cyclase activity, whereas another phosphodiesterase inhibitor, RO-20-1724, failed to iiinfluence the effect of adenosine. Adenosine itself, and not a metabolite of adenosine is the stimulator of adenylate cyclase, since it was neither phosphorylated nor deaminated appreciably by the particulate fraction. The particulate fraction did not convert substrate ATP to adenosine in amounts sufficient to enhance adenylate cyclase. The stimulatory effect of adenosine was maximal at 1.2 mM Mg2+, declined with increases in the Mg2+ concentration, and was replaced by inhibition at 20 mM Mg2+. At 2.4 mM Mg2+, basal adenylate cyclase activity peaked at 1.1 mM ATP, and was inhibited by higher ATP concentrations. The magnitude of adenosine stimulation was greater at inhibitory concentrations of ATP than at concentrations which yielded maximum activity. The results suggest that the previously demonstrated ability of adenosine to increase cyclic 3'5' AMP levels in intact bone cells stems from its effect on adenylate cyclase. Adenosine may act by modifying the regulatory nfluence of free Mg2+, uncomplexed ATP, (or both), on adenylate cyclase. Theophylline appears to interfere with the action of adenosine by a mechanism which is distinct from its capacity to inhibit cyclic AMP phosphodiesterase activity. (Endocrinology 99:901,1976)", "contents": "Adenosine-mediated stimulation of bone cell adenylate cyclase activity. Adenosine rapidly stimulated adenylate cyclase activity but did not modify cyclic AMP degradation when added to a particulate fraction prepared from isolated bone cells. The effect of adenosine was one-half maximal at 5-10 micronM, and was not mimicked by 5' AMP, inosine, guanosine, uridine, adenine, or ribose. Basal and adenosine-stimulated adenylate cyclase activites were directly proportional to the concentration of particulate protein in the assay system. Theophylline decreased the degree to which adenosine stimulated adenylate cyclase activity, whereas another phosphodiesterase inhibitor, RO-20-1724, failed to iiinfluence the effect of adenosine. Adenosine itself, and not a metabolite of adenosine is the stimulator of adenylate cyclase, since it was neither phosphorylated nor deaminated appreciably by the particulate fraction. The particulate fraction did not convert substrate ATP to adenosine in amounts sufficient to enhance adenylate cyclase. The stimulatory effect of adenosine was maximal at 1.2 mM Mg2+, declined with increases in the Mg2+ concentration, and was replaced by inhibition at 20 mM Mg2+. At 2.4 mM Mg2+, basal adenylate cyclase activity peaked at 1.1 mM ATP, and was inhibited by higher ATP concentrations. The magnitude of adenosine stimulation was greater at inhibitory concentrations of ATP than at concentrations which yielded maximum activity. The results suggest that the previously demonstrated ability of adenosine to increase cyclic 3'5' AMP levels in intact bone cells stems from its effect on adenylate cyclase. Adenosine may act by modifying the regulatory nfluence of free Mg2+, uncomplexed ATP, (or both), on adenylate cyclase. Theophylline appears to interfere with the action of adenosine by a mechanism which is distinct from its capacity to inhibit cyclic AMP phosphodiesterase activity. (Endocrinology 99:901,1976)"} {"id": "PMID:182473", "title": "Effect of glucose on adenosine 3', 5'-monophosphate levels in rat pancreatic islets.", "content": "Time course of the changes in insulin release and cyclic AMP levels in isolated rat islets incubated in media containing 5 or 16.7 mM of glucose were followed. The higher glucose concentration caused a slight but significant increase of cyclic AMP levels after 10 min incubation, but not 5 min incubation, whereas the stimulation of insulin release by 16.7 mM of glucose was apparent in both incubation times. Theophylline increased cyclic AMP levels markedly but did not stimulate insulin release when the glucose concentration was 5 mM. A slight augmentation by theophylline of insulin release was observed in the incubation medium containing 16.7 mM glucose. All these findings suggest that the elevation of cyclic AMP in islets may not play a role for the initiation of the insulin release induced by glucose, though it may act to modulate the glucose effect.", "contents": "Effect of glucose on adenosine 3', 5'-monophosphate levels in rat pancreatic islets. Time course of the changes in insulin release and cyclic AMP levels in isolated rat islets incubated in media containing 5 or 16.7 mM of glucose were followed. The higher glucose concentration caused a slight but significant increase of cyclic AMP levels after 10 min incubation, but not 5 min incubation, whereas the stimulation of insulin release by 16.7 mM of glucose was apparent in both incubation times. Theophylline increased cyclic AMP levels markedly but did not stimulate insulin release when the glucose concentration was 5 mM. A slight augmentation by theophylline of insulin release was observed in the incubation medium containing 16.7 mM glucose. All these findings suggest that the elevation of cyclic AMP in islets may not play a role for the initiation of the insulin release induced by glucose, though it may act to modulate the glucose effect."} {"id": "PMID:182474", "title": "Direct evidence on incorporation of the receptor into the nuclei of rat ventral prostate in the form of the complex with dihydrotestosterone.", "content": "Cytosol 9S receptor was prepared from the supernatant fluid at 105,000 X g of rat prostate homogenates by a Sephadex G-100 gel chromatography, and was labeled with 131I. The 131I-labeled 9S receptor retained the activity of forming a complex with 3H-dihydrotestosterone, similarly to the intact cytosol receptor, when examined by a sucrose density gradient centrifugation. When the 131I-labeled cytosol 9S receptor was incubated with isolated prostatic nuclei in the presence of 3H-dihydrotestosterone, it was found that the 131I-labeled receptor was directly incorporated into the nuclei in a form of the complex bound to 3H-dihydrotestosterone. 131I-Labeled receptor-3H-dihydrotestosterone complex which was incorporated into the nuclei was extracted with 0.5 M KCl solution, and the nuclear complex sedimented with a velocity of 5S. The incorporation of 131I-labeled receptor-3H-dihydrotestosterone complex into the nuclei increased along with the raised temperature of incubation, whereas association of the complex with the chromatin reached maximum at 35 degrees C and then decreased gradually beyond this temperature. In the time course study, either the incorporation of the complex into the nuclei or the association with the chromatin reached the maximal levels within 10 min and leveled off up to 60 min. On the other hand, 131I-labeled serum protein was far less efficiently incorporated into the nuclei than the radioiodinated 9S receptor, and association of the serum protein with the chromatin was limited to a very little extent. The 131I-labeled 9S receptor-dihydrotestosterone complex associated with the chromatin was found to be preferably distributed into the non-histone protein as well as the DNA itself of the chromatin. The radioactivity lost by dehistonization of the chromatin was almost negligible. Furthermore, the cytosol 9S receptor fraction bound to 3H-dihydrotestosterone was purified about 100 fold by the two consecutive column chromatographies. The partially purified receptor fraction which was labeled with radioiodine incorporated mostly into non-histone protein and DNA fractions.", "contents": "Direct evidence on incorporation of the receptor into the nuclei of rat ventral prostate in the form of the complex with dihydrotestosterone. Cytosol 9S receptor was prepared from the supernatant fluid at 105,000 X g of rat prostate homogenates by a Sephadex G-100 gel chromatography, and was labeled with 131I. The 131I-labeled 9S receptor retained the activity of forming a complex with 3H-dihydrotestosterone, similarly to the intact cytosol receptor, when examined by a sucrose density gradient centrifugation. When the 131I-labeled cytosol 9S receptor was incubated with isolated prostatic nuclei in the presence of 3H-dihydrotestosterone, it was found that the 131I-labeled receptor was directly incorporated into the nuclei in a form of the complex bound to 3H-dihydrotestosterone. 131I-Labeled receptor-3H-dihydrotestosterone complex which was incorporated into the nuclei was extracted with 0.5 M KCl solution, and the nuclear complex sedimented with a velocity of 5S. The incorporation of 131I-labeled receptor-3H-dihydrotestosterone complex into the nuclei increased along with the raised temperature of incubation, whereas association of the complex with the chromatin reached maximum at 35 degrees C and then decreased gradually beyond this temperature. In the time course study, either the incorporation of the complex into the nuclei or the association with the chromatin reached the maximal levels within 10 min and leveled off up to 60 min. On the other hand, 131I-labeled serum protein was far less efficiently incorporated into the nuclei than the radioiodinated 9S receptor, and association of the serum protein with the chromatin was limited to a very little extent. The 131I-labeled 9S receptor-dihydrotestosterone complex associated with the chromatin was found to be preferably distributed into the non-histone protein as well as the DNA itself of the chromatin. The radioactivity lost by dehistonization of the chromatin was almost negligible. Furthermore, the cytosol 9S receptor fraction bound to 3H-dihydrotestosterone was purified about 100 fold by the two consecutive column chromatographies. The partially purified receptor fraction which was labeled with radioiodine incorporated mostly into non-histone protein and DNA fractions."} {"id": "PMID:182475", "title": "Cushing's syndrome due to huge adrenocortical multinodular hyperplasia.", "content": "A case of Cushing's syndrome due to huge adrenocortial multinodular hyperplasia who was shown to be hyperresponsive to ACTH administration, unresponsive to metyrapone administration and resistant to dexamethasone high dose suppression was reported. After two years' duration of his symptoms, the multinodular adrenals weighing 161 g in total were removed by bilateral adrenalectomy which abolished his symptoms. Postoperatively, plasma ACTH rose gradually to above normal levels, suggesting the presence of primary disorder in the hypothalamus-pituitary axis.", "contents": "Cushing's syndrome due to huge adrenocortical multinodular hyperplasia. A case of Cushing's syndrome due to huge adrenocortial multinodular hyperplasia who was shown to be hyperresponsive to ACTH administration, unresponsive to metyrapone administration and resistant to dexamethasone high dose suppression was reported. After two years' duration of his symptoms, the multinodular adrenals weighing 161 g in total were removed by bilateral adrenalectomy which abolished his symptoms. Postoperatively, plasma ACTH rose gradually to above normal levels, suggesting the presence of primary disorder in the hypothalamus-pituitary axis."} {"id": "PMID:182476", "title": "Some biological properties of human chorionic follicle stimulating hormone.", "content": "The biological properties of human chorionic FSH (hCFSH) for rat ovaries were investigated. Highly purified hCFSH had similar response to the ovarian augmentation test as bovine FSH and significantly enhanced 3H-thymidine uptake by granulosa cells and theca cells in the ovary of hypophysectomized rat. In contrast, highly purified hCG little responded to the ovarian augmentation test and had no effect on 3H-thymidine uptake by the ovary. These results indicate that hCFSH may promote the follicular growth of ovary resulting from granulosa cell proliferation and its enlargement. In addition, freshly harvested porcine granulosa cells were employed in an in vitro system to investigate specific binding of hCFSH to ovarian receptor. Radioiodinated hCFSH (125I-hCFSH) and hCG (125I-hCG) were respectively incubated with cell suspensions. Binding of these hormone preparations was proportional to the cell number and increased with the time of incubation through 120 minutes. The binding ability of 125I-hCFSH to the cells was greater than that of 125I-hCG. Increasing concentrations of unlabeled hCFSH in the incubation mixture progressively inhibited the uptake of 125I-hCFSH by granulosa cells. Unlabeled hCG was not able to compete with 125I-HCFSH binding. The similar phenomenon to inhibit the binding of 125I-hCG to the cells was also recognized in the presence of unlabeled hCG. These findings suggest that granulosa cell has at least two different types of receptor sites: one for hCFSH and the other for hCG.", "contents": "Some biological properties of human chorionic follicle stimulating hormone. The biological properties of human chorionic FSH (hCFSH) for rat ovaries were investigated. Highly purified hCFSH had similar response to the ovarian augmentation test as bovine FSH and significantly enhanced 3H-thymidine uptake by granulosa cells and theca cells in the ovary of hypophysectomized rat. In contrast, highly purified hCG little responded to the ovarian augmentation test and had no effect on 3H-thymidine uptake by the ovary. These results indicate that hCFSH may promote the follicular growth of ovary resulting from granulosa cell proliferation and its enlargement. In addition, freshly harvested porcine granulosa cells were employed in an in vitro system to investigate specific binding of hCFSH to ovarian receptor. Radioiodinated hCFSH (125I-hCFSH) and hCG (125I-hCG) were respectively incubated with cell suspensions. Binding of these hormone preparations was proportional to the cell number and increased with the time of incubation through 120 minutes. The binding ability of 125I-hCFSH to the cells was greater than that of 125I-hCG. Increasing concentrations of unlabeled hCFSH in the incubation mixture progressively inhibited the uptake of 125I-hCFSH by granulosa cells. Unlabeled hCG was not able to compete with 125I-HCFSH binding. The similar phenomenon to inhibit the binding of 125I-hCG to the cells was also recognized in the presence of unlabeled hCG. These findings suggest that granulosa cell has at least two different types of receptor sites: one for hCFSH and the other for hCG."} {"id": "PMID:182477", "title": "Changes in cyclic AMP level of rat thyroid by acute and chronic stimulation of thyrotropin in vivo.", "content": "To assess a possible postmortem change in the level of cyclic AMP, the thyroids were snap-frozen at various time intervals after removal. Rats were fed a low-iodine diet (LID) with PTU for 2 weeks and a week after PTU discontinuation (PTU withdrawal). In all cases, the cyclic AMP level tended to increase as time elapsed from removing till fixing the thyroids, but in the PTU withdrawal group, the level was rapidly increased 2-fold after 5 min. In an acute experiment, the thyroids were removed under anesthesia and frozen rapidly. Intravenous administration of ovine thyrotropin (250 mU) and TRH (500 ng) brought about a rapid increase in the thyroidal level of cyclic AMP to 40% to 20% over the control level. Two weeks after PTU treatment, circulating thyrotropin was increased to a maximum of 19-fold and a further enhancement (\"rebound\") was observed after PTU withdrawal. PTU treatment led to an increase in the thyroidal level of cyclis AMP pre mug DNA to 60% over the control value. Following PTU withdrawal, the rise in the level of cyclic AMP returned to the normal level. However, there was no change in the concentration when it was expressed as per mg wet tissue weight. Therefore, the increase in the thyroidal concentration of cyclic AMP per mug of DNA may be due to an increase in volume of the follicular cells.", "contents": "Changes in cyclic AMP level of rat thyroid by acute and chronic stimulation of thyrotropin in vivo. To assess a possible postmortem change in the level of cyclic AMP, the thyroids were snap-frozen at various time intervals after removal. Rats were fed a low-iodine diet (LID) with PTU for 2 weeks and a week after PTU discontinuation (PTU withdrawal). In all cases, the cyclic AMP level tended to increase as time elapsed from removing till fixing the thyroids, but in the PTU withdrawal group, the level was rapidly increased 2-fold after 5 min. In an acute experiment, the thyroids were removed under anesthesia and frozen rapidly. Intravenous administration of ovine thyrotropin (250 mU) and TRH (500 ng) brought about a rapid increase in the thyroidal level of cyclic AMP to 40% to 20% over the control level. Two weeks after PTU treatment, circulating thyrotropin was increased to a maximum of 19-fold and a further enhancement (\"rebound\") was observed after PTU withdrawal. PTU treatment led to an increase in the thyroidal level of cyclis AMP pre mug DNA to 60% over the control value. Following PTU withdrawal, the rise in the level of cyclic AMP returned to the normal level. However, there was no change in the concentration when it was expressed as per mg wet tissue weight. Therefore, the increase in the thyroidal concentration of cyclic AMP per mug of DNA may be due to an increase in volume of the follicular cells."} {"id": "PMID:182478", "title": "Biological activity of synthetic corticotrophin with short chain lengths in the rabbit.", "content": "The andrenocorticotrophic effect of a synthetic substituted adrenocorticortophic hormone (ACTH), alpha-1-18NH2-D-Ser1-Lys17, 18-ACTH (CIBA 47, 795-Ba) has been compared with that of alpha1-24-ACTH (tetracosactide), alpha1-24-ACTH depot (tetracosactide depot) and alpha1-18NH2-Gly1-ACTH (giractide) in the rabbit. Plasma corticosteroid levels after salin injection were higher in the afternoon than in the morning. The highest value was observed at 3 p.m. 41,795-Ba, either given intravenously or intramuscularly, was shown to be the most potent peptide followed by tetrocosactide depot and was 15 times more potent than tetracosactide and giractide in steroidogenic activity in the rabbit. The intravenous administration of 41,795-Ba caused more sustained stimulation of the adrenal cortex than the intramuscular injection. These results reveal the diurnal variation pattern of the pitutitary-adrenal axis of the rabbit similar to that of the rat and also confirm the finding that alpha1-18NH2-Dser1-Lys17, 18-ACTH is a potent adrenocorticotrophic peptide without the addition of any agent to delay its absorption in the rabbit.", "contents": "Biological activity of synthetic corticotrophin with short chain lengths in the rabbit. The andrenocorticotrophic effect of a synthetic substituted adrenocorticortophic hormone (ACTH), alpha-1-18NH2-D-Ser1-Lys17, 18-ACTH (CIBA 47, 795-Ba) has been compared with that of alpha1-24-ACTH (tetracosactide), alpha1-24-ACTH depot (tetracosactide depot) and alpha1-18NH2-Gly1-ACTH (giractide) in the rabbit. Plasma corticosteroid levels after salin injection were higher in the afternoon than in the morning. The highest value was observed at 3 p.m. 41,795-Ba, either given intravenously or intramuscularly, was shown to be the most potent peptide followed by tetrocosactide depot and was 15 times more potent than tetracosactide and giractide in steroidogenic activity in the rabbit. The intravenous administration of 41,795-Ba caused more sustained stimulation of the adrenal cortex than the intramuscular injection. These results reveal the diurnal variation pattern of the pitutitary-adrenal axis of the rabbit similar to that of the rat and also confirm the finding that alpha1-18NH2-Dser1-Lys17, 18-ACTH is a potent adrenocorticotrophic peptide without the addition of any agent to delay its absorption in the rabbit."} {"id": "PMID:182479", "title": "[The fine structure of the rat pineal and the influence of anti-androgens and castroation].", "content": "The pineal body, along with the hypothalamus-hypophysis system, is in the centre of sexual hormone regulation and, in addition to other functions, develops an antigonadotropic action through its organ specific hormone (melatonin). In order to clarify further open questions and to analyse more closely the morphology of the fine structure of the organ, light and electron microscopic studies were made of the pineal bodies of sexually mature male rats after hormonal castration by the administration of cyproterone and cyproterone acetate. The findings were compared with results obtained in the pineal bodies of surgically castrated animals of the same strain. Epiphysectomy was performed 3, 6, 9 and 12 weeks after castration or application of antiandrogen. In the pineal bodies, \"light\" and \"dark\" pineal cells and an interstitial cell form could be detected electronmicroscopically. The interstitial cells are found localised near the vessels in particular; their ramifications reach into the perivascular cleft. The light pineal cells preponderate and react essentially in the series; they are therefore considered as the really active form of parenchyma cells. Increased cell activity is already observed three weeks after treatment with antiandrogen: the nucleoli are enlarged, the ribosomes, the mitochondria and ergastoplasm are increased, the endoplasmic reticulum quantified and extended, and also the Golgi regions. The cells are consequently enlarged. Lysosomes also appear which frequently enter the liposomes. The changes in the liposomes after application of antiandrogen are remarkable. Initially they are evacuated, partially drawn out. Later the liposomes are enlarged and increased and often fill the cell body. These pineocytes form an appendage to the castration cells of the hypophysis. The liposomes are in a very close spatial, formal genetic relationship to the Golgi apparatus and to the rough walled reticulum. The larger liposomes apparently arise also through the confluence of smaller ones. Three structural elements of the liposomes could be indentifed: a homogenous, a lamellar and a granular component. The fine morphological reactions are most marked after cyproterone acetate. For the first time, bundles of \"microtubuli\" are described, the significance of which is not yet clear. They probably arise from the endoplasmic reticulum, they are only found after cyproterone acetate and are presumably due to the gestagen component of the cyproterone acetate. These structures have not previously been observed, either in pineal bodies or in other organs. The structures found after antiandrogen are not so outstandingly recognisable after surgical castration. The biological differences of the surgical compared with hormonal castration therefore seem to be reflected in the cell picture of the pineocytes. Consequently, the pineal body, after treatment with antiandrogen, shows cytostructural changes similar to those of increased anabolism...", "contents": "[The fine structure of the rat pineal and the influence of anti-androgens and castroation]. The pineal body, along with the hypothalamus-hypophysis system, is in the centre of sexual hormone regulation and, in addition to other functions, develops an antigonadotropic action through its organ specific hormone (melatonin). In order to clarify further open questions and to analyse more closely the morphology of the fine structure of the organ, light and electron microscopic studies were made of the pineal bodies of sexually mature male rats after hormonal castration by the administration of cyproterone and cyproterone acetate. The findings were compared with results obtained in the pineal bodies of surgically castrated animals of the same strain. Epiphysectomy was performed 3, 6, 9 and 12 weeks after castration or application of antiandrogen. In the pineal bodies, \"light\" and \"dark\" pineal cells and an interstitial cell form could be detected electronmicroscopically. The interstitial cells are found localised near the vessels in particular; their ramifications reach into the perivascular cleft. The light pineal cells preponderate and react essentially in the series; they are therefore considered as the really active form of parenchyma cells. Increased cell activity is already observed three weeks after treatment with antiandrogen: the nucleoli are enlarged, the ribosomes, the mitochondria and ergastoplasm are increased, the endoplasmic reticulum quantified and extended, and also the Golgi regions. The cells are consequently enlarged. Lysosomes also appear which frequently enter the liposomes. The changes in the liposomes after application of antiandrogen are remarkable. Initially they are evacuated, partially drawn out. Later the liposomes are enlarged and increased and often fill the cell body. These pineocytes form an appendage to the castration cells of the hypophysis. The liposomes are in a very close spatial, formal genetic relationship to the Golgi apparatus and to the rough walled reticulum. The larger liposomes apparently arise also through the confluence of smaller ones. Three structural elements of the liposomes could be indentifed: a homogenous, a lamellar and a granular component. The fine morphological reactions are most marked after cyproterone acetate. For the first time, bundles of \"microtubuli\" are described, the significance of which is not yet clear. They probably arise from the endoplasmic reticulum, they are only found after cyproterone acetate and are presumably due to the gestagen component of the cyproterone acetate. These structures have not previously been observed, either in pineal bodies or in other organs. The structures found after antiandrogen are not so outstandingly recognisable after surgical castration. The biological differences of the surgical compared with hormonal castration therefore seem to be reflected in the cell picture of the pineocytes. Consequently, the pineal body, after treatment with antiandrogen, shows cytostructural changes similar to those of increased anabolism..."} {"id": "PMID:182480", "title": "[The cortisol concentration in plasma of newborn piglets and after ACTH loading].", "content": "In plasma of newborn piglets 12.6 +/- 2.9 mug cortisol/100 ml was estimated radioimmunologically. During the first 24 hours of life the concentration decreases to 1/3 of the starting level. After application of 5 IU ACTH/kg body weight, there was in newborn as in 5-day-old piglets an increase in the concentration of cortisol, while an influence on the level of glucose in plasma could not be detected in 0-day-old animals.", "contents": "[The cortisol concentration in plasma of newborn piglets and after ACTH loading]. In plasma of newborn piglets 12.6 +/- 2.9 mug cortisol/100 ml was estimated radioimmunologically. During the first 24 hours of life the concentration decreases to 1/3 of the starting level. After application of 5 IU ACTH/kg body weight, there was in newborn as in 5-day-old piglets an increase in the concentration of cortisol, while an influence on the level of glucose in plasma could not be detected in 0-day-old animals."} {"id": "PMID:182484", "title": "Prevention of dietary induction of rat liver glucose-6-phosphate dehydrogenase by cyclic adenosine 3'.5'-monophosphate and its elimination by glucose prefeeding.", "content": "Glucagon, epinephrine and cyclic adenosine 3',5'-monophosphate (cyclic AMP) prevented the induction of liver glucose-6-phosphate dehydrogenase (G6PD) by refeeding a glucose-casein mixture to starved rats. The prevention by these agents occurred without any change in the amount of diet consumed. When the injection of cyclic AMP and the refeeding of glucose-casein diet were initiated simultaneously, there was an inhibiton of G6PD induction depending upon the dose and frequency of cyclic AMP administration during the period of refeeding, while when cyclic AMP was given later than 12 h of the refeeding, the lag period for induction of this enzyme, there was no preventive effect. A glucose prefeeding was also found to counteract the inhibitory effect of cyclic AMP on G6PD induction by the subsequent glucose-casein refeeding. The present data together with the elimination of actinomycin D effect by the glucose prefeeding suggest that the inhibitory effect of cyclic AMP on the induction of G6PD dehydrogenase is exerted at the level of transcription.", "contents": "Prevention of dietary induction of rat liver glucose-6-phosphate dehydrogenase by cyclic adenosine 3'.5'-monophosphate and its elimination by glucose prefeeding. Glucagon, epinephrine and cyclic adenosine 3',5'-monophosphate (cyclic AMP) prevented the induction of liver glucose-6-phosphate dehydrogenase (G6PD) by refeeding a glucose-casein mixture to starved rats. The prevention by these agents occurred without any change in the amount of diet consumed. When the injection of cyclic AMP and the refeeding of glucose-casein diet were initiated simultaneously, there was an inhibiton of G6PD induction depending upon the dose and frequency of cyclic AMP administration during the period of refeeding, while when cyclic AMP was given later than 12 h of the refeeding, the lag period for induction of this enzyme, there was no preventive effect. A glucose prefeeding was also found to counteract the inhibitory effect of cyclic AMP on G6PD induction by the subsequent glucose-casein refeeding. The present data together with the elimination of actinomycin D effect by the glucose prefeeding suggest that the inhibitory effect of cyclic AMP on the induction of G6PD dehydrogenase is exerted at the level of transcription."} {"id": "PMID:182485", "title": "An approach to the anabolic action of androgens by an experimental system.", "content": "As skeletal muscle is more developed in the male than in the female, it is supposed that androgens might be responsible for myotrophic or anabolic action. In this respect, many studies were made to try to answer the question: are androgens (or some of their metabolites) responsible for myotrophic action and by what mechanism? Do they act directly on skeletal muscle as on other target organs, or have they an indirect action on muscle, perhaps through a secondary stimulant (for instance synthesized in the liver)? Evidence is now presented that, in the rat's skeletal muscle, androgens likely act through the binding to a cytosoluble receptor, as they do in the ventral prostate. This receptor has analogous properties to all other androgen receptors. It is a proteinaceous (pronase sensible) \"8S\" component binding testosterone and androstanolone with high affinity and small capacity; it does not bind androstanediols. This finding and the increased incorporation of 3H-thymidine in nuclei and increased protein synthesis obtained in muscle cell culture after action of testosterone favour the concept that muscular cells are direct targets of androgens in skeletal muscles. Presently, the steroid specificity of receptor binding cannot be assessed quantitatively with crude cytosol preparation. While in ventral prostate, androstanolone has a higher affinity, the binding experiments have not yet indicated in muscle if the higher affinity of testosterone is related to differential binding of the two steroids, or to the complex effects of enzymes present in the extracts. In fact, evidence was obtained for 5alpha-reductase and 3alpha,beta-hydroxysteroid reductase activities under the same experimental conditions as for binding determinations. Therefore, the apparent antrostanolone binding in muscle could be lowered by transformation into androstanediols not binding to receptor, or the increase of apparent testosterone binding due to transformation into androstanolone. So the problem of whether testosterone or androstanolone or another natural steroid is the most effective myotrophic hormone in rat skeletal muscle remains unsolved. However, this animal model allows the study of certain interesting aspects of action of androgens on muscle. When receptor preparations are partially purified and not contaminated by metabolizing enzymes, different natural or synthetic steroids can be tested as to their affinity and anabolic effectiveness in muscle. It would be of pharmacological interest if receptor diversity made it possible to distinguish myotrophic action from virilizing activities. This in vitro system allows studying the mechanism of action of molecules which could have in vivo an anti-androgen effect and it is remarkable that radioactive testosterone and androstanolone can compete for receptor binding by an excess of estradiol, progesterone and cyproterone acetate...", "contents": "An approach to the anabolic action of androgens by an experimental system. As skeletal muscle is more developed in the male than in the female, it is supposed that androgens might be responsible for myotrophic or anabolic action. In this respect, many studies were made to try to answer the question: are androgens (or some of their metabolites) responsible for myotrophic action and by what mechanism? Do they act directly on skeletal muscle as on other target organs, or have they an indirect action on muscle, perhaps through a secondary stimulant (for instance synthesized in the liver)? Evidence is now presented that, in the rat's skeletal muscle, androgens likely act through the binding to a cytosoluble receptor, as they do in the ventral prostate. This receptor has analogous properties to all other androgen receptors. It is a proteinaceous (pronase sensible) \"8S\" component binding testosterone and androstanolone with high affinity and small capacity; it does not bind androstanediols. This finding and the increased incorporation of 3H-thymidine in nuclei and increased protein synthesis obtained in muscle cell culture after action of testosterone favour the concept that muscular cells are direct targets of androgens in skeletal muscles. Presently, the steroid specificity of receptor binding cannot be assessed quantitatively with crude cytosol preparation. While in ventral prostate, androstanolone has a higher affinity, the binding experiments have not yet indicated in muscle if the higher affinity of testosterone is related to differential binding of the two steroids, or to the complex effects of enzymes present in the extracts. In fact, evidence was obtained for 5alpha-reductase and 3alpha,beta-hydroxysteroid reductase activities under the same experimental conditions as for binding determinations. Therefore, the apparent antrostanolone binding in muscle could be lowered by transformation into androstanediols not binding to receptor, or the increase of apparent testosterone binding due to transformation into androstanolone. So the problem of whether testosterone or androstanolone or another natural steroid is the most effective myotrophic hormone in rat skeletal muscle remains unsolved. However, this animal model allows the study of certain interesting aspects of action of androgens on muscle. When receptor preparations are partially purified and not contaminated by metabolizing enzymes, different natural or synthetic steroids can be tested as to their affinity and anabolic effectiveness in muscle. It would be of pharmacological interest if receptor diversity made it possible to distinguish myotrophic action from virilizing activities. This in vitro system allows studying the mechanism of action of molecules which could have in vivo an anti-androgen effect and it is remarkable that radioactive testosterone and androstanolone can compete for receptor binding by an excess of estradiol, progesterone and cyproterone acetate..."} {"id": "PMID:182486", "title": "Encephalitis caused by louping ill virus in a group of horses in Ireland.", "content": "An outbreak of LI infection in a group of free range horses is described. Three of 4 horses displayed signs of CNS disturbance and 2 of these died after illnesses ranging from 2-12 days duration. In both cases a variable degree of viral polioencephalomyelitis was observed. A virus antigenically indistinguishable from a reference strain of LI virus was isolated from the brain and cervical cord of a 3 y.o. draft mare. Serum samples obtained from 3 of the horses contained HI, CF, precipitating and neutralising antibodies to LI virus, with a rise in antibody titre being demonstrated in 2 animals.", "contents": "Encephalitis caused by louping ill virus in a group of horses in Ireland. An outbreak of LI infection in a group of free range horses is described. Three of 4 horses displayed signs of CNS disturbance and 2 of these died after illnesses ranging from 2-12 days duration. In both cases a variable degree of viral polioencephalomyelitis was observed. A virus antigenically indistinguishable from a reference strain of LI virus was isolated from the brain and cervical cord of a 3 y.o. draft mare. Serum samples obtained from 3 of the horses contained HI, CF, precipitating and neutralising antibodies to LI virus, with a rise in antibody titre being demonstrated in 2 animals."} {"id": "PMID:182487", "title": "Efficacy of Japanese encephalitis vaccine in horses.", "content": "The efficacy of Japanese encephalitis vaccine in horses has been described from the effect of mass vaccination on the local prevalence of the disease in horses in each district of Hokkaido, Japan.", "contents": "Efficacy of Japanese encephalitis vaccine in horses. The efficacy of Japanese encephalitis vaccine in horses has been described from the effect of mass vaccination on the local prevalence of the disease in horses in each district of Hokkaido, Japan."} {"id": "PMID:182488", "title": "Binding of a metyrapone spin label to microsomal cytochrome P-450.", "content": "Probing of the active site of microsomal cytochrome P-450 was carried out with a spin label derived from 2-methyl-1,2-bis(3-pyridyl)-1-propanone (metyrapone). Its optical binding spectra to cytochrome P-450 resemble the spectra with metyrapone. The electron paramagnetic resonance spectrum of the spin label in microsomes indicates binding with strong immobilization. Since the apparent optical and EPR binding constants agree very well (Ks approximately 2-10(-5) M), and metyrapone is found to displace the spin label, we conclude, that the spin label binds to the active site of cytochrome P-450. Addition of detergents or an increase in temperature mobilizes the bound spin label slightly. The EPR signal accounts for only 60% of the bound spin label due to its dipolar interaction with the low-spin ferric heme of cytochrome P-450. From this finding, the distance between nitroxide and iron is evaluated to be 11 A. This supports the model that one of the pyridine nitrogens of metyrapone is coordinated to the iron of cytochrome P-450. The bound spin label shows virtually no interaction with ferricyanide as if the active site of cytochrome P-450 is a hydrophobic pocket not accessible to ions.", "contents": "Binding of a metyrapone spin label to microsomal cytochrome P-450. Probing of the active site of microsomal cytochrome P-450 was carried out with a spin label derived from 2-methyl-1,2-bis(3-pyridyl)-1-propanone (metyrapone). Its optical binding spectra to cytochrome P-450 resemble the spectra with metyrapone. The electron paramagnetic resonance spectrum of the spin label in microsomes indicates binding with strong immobilization. Since the apparent optical and EPR binding constants agree very well (Ks approximately 2-10(-5) M), and metyrapone is found to displace the spin label, we conclude, that the spin label binds to the active site of cytochrome P-450. Addition of detergents or an increase in temperature mobilizes the bound spin label slightly. The EPR signal accounts for only 60% of the bound spin label due to its dipolar interaction with the low-spin ferric heme of cytochrome P-450. From this finding, the distance between nitroxide and iron is evaluated to be 11 A. This supports the model that one of the pyridine nitrogens of metyrapone is coordinated to the iron of cytochrome P-450. The bound spin label shows virtually no interaction with ferricyanide as if the active site of cytochrome P-450 is a hydrophobic pocket not accessible to ions."} {"id": "PMID:182489", "title": "Solubilization and purification of rat liver microsomal 1,2-diacylglycerol: CDP-choline cholinephosphotransferase and 1,2-diacylglycerol: CDP-ethanolamine ethanolaminephosphotransferase.", "content": "1. The procedure, which involved 2-step sonication of microsomes at pH 7.4 and then at pH 8.5 in the presence of sodium deoxycholate and subsequent dialysis, resulted in 4-5-fold purification of choline-phosphotransferase and ethanolaminephosphotransferase with the yield of 40-50%. 2. Ethanolaminephosphotransferase was further purified 8.5-fold over microsomes by sucrose density gradient centrifugation of the partially purified preparation, while cholinephosphotransferase activity was considerably lost during this procedure. No separation of the two transferases from each other was achieved at this step. 3. Cholinephosphotransferase required Mg2+ as cofactor, and microsomal phospholipids for its maximal activity. On the other hand, Mn2+ was more effective than Mg2+ as cofactor for ethanol aminephosphotransferase, and this enzyme was inhibited by microsomal phospholipids. 4. Both transferases were stimulated several-fold by sodium deoxycholate and also showed similar optimal pH ranging from pH 8.0 to 8.5. 5. Km values for 1,2-diacylglycerol emulsion were 81.0 muM for cholinephosphotransferase and 63.0 muM for ethanolaminephosphotransferase, respectively. CDP-choline and CDP-ethanolamine competitively inhibited, with the same Ki value (both 350 muM), ethanolaminephosphotransferase and cholinephosphotransferase, respectively. The Ki values obtained were much greater than the corresponding Km values for the cytidine substrates (36.4 muM for CDP-choline and 22.0 muM for CDP-ethanolamine). 6. The partially purified enzymes were further treated with Triton X-100. When enzyme activities were assayed with Mg2+, cholinephosphotransferase, although considerably inactivated, was partially separated from ethanolaminephosphotransferase by sucrose density gradient centrifugation of Triton-treated preparations. Furthermore, cholinephosphotransferase (but not ethanol-aminephosphotransferase) itself was partially separated into Mg2+ -requiring and Mn2+ -requiring components. In contrast, ethanolaminephosphotransferase assayed with either Mg2+ or Mn2+ formed a single peak together with Mn2+ -requiring cholinephosphotransferase.", "contents": "Solubilization and purification of rat liver microsomal 1,2-diacylglycerol: CDP-choline cholinephosphotransferase and 1,2-diacylglycerol: CDP-ethanolamine ethanolaminephosphotransferase. 1. The procedure, which involved 2-step sonication of microsomes at pH 7.4 and then at pH 8.5 in the presence of sodium deoxycholate and subsequent dialysis, resulted in 4-5-fold purification of choline-phosphotransferase and ethanolaminephosphotransferase with the yield of 40-50%. 2. Ethanolaminephosphotransferase was further purified 8.5-fold over microsomes by sucrose density gradient centrifugation of the partially purified preparation, while cholinephosphotransferase activity was considerably lost during this procedure. No separation of the two transferases from each other was achieved at this step. 3. Cholinephosphotransferase required Mg2+ as cofactor, and microsomal phospholipids for its maximal activity. On the other hand, Mn2+ was more effective than Mg2+ as cofactor for ethanol aminephosphotransferase, and this enzyme was inhibited by microsomal phospholipids. 4. Both transferases were stimulated several-fold by sodium deoxycholate and also showed similar optimal pH ranging from pH 8.0 to 8.5. 5. Km values for 1,2-diacylglycerol emulsion were 81.0 muM for cholinephosphotransferase and 63.0 muM for ethanolaminephosphotransferase, respectively. CDP-choline and CDP-ethanolamine competitively inhibited, with the same Ki value (both 350 muM), ethanolaminephosphotransferase and cholinephosphotransferase, respectively. The Ki values obtained were much greater than the corresponding Km values for the cytidine substrates (36.4 muM for CDP-choline and 22.0 muM for CDP-ethanolamine). 6. The partially purified enzymes were further treated with Triton X-100. When enzyme activities were assayed with Mg2+, cholinephosphotransferase, although considerably inactivated, was partially separated from ethanolaminephosphotransferase by sucrose density gradient centrifugation of Triton-treated preparations. Furthermore, cholinephosphotransferase (but not ethanol-aminephosphotransferase) itself was partially separated into Mg2+ -requiring and Mn2+ -requiring components. In contrast, ethanolaminephosphotransferase assayed with either Mg2+ or Mn2+ formed a single peak together with Mn2+ -requiring cholinephosphotransferase."} {"id": "PMID:182490", "title": "Cell-cycle dependence of two nuclear histone kinase enzyme activities.", "content": "Growth-associated histone kinases have been extracted from Physarum polycephalum nuclei and resolved into two components by ion-exchange chromatography. The two component activities have different substrate specificities and different times of appearance in the cell cycle. It is proposed that the enzyme(s) phosphorylate H1 histone in vivo in G2 phase, possibly sequentially in time at different sites in the H1 amino acid sequence.", "contents": "Cell-cycle dependence of two nuclear histone kinase enzyme activities. Growth-associated histone kinases have been extracted from Physarum polycephalum nuclei and resolved into two components by ion-exchange chromatography. The two component activities have different substrate specificities and different times of appearance in the cell cycle. It is proposed that the enzyme(s) phosphorylate H1 histone in vivo in G2 phase, possibly sequentially in time at different sites in the H1 amino acid sequence."} {"id": "PMID:182491", "title": "Studies on the structure and function of chick-oviduct chromatin. 2. Biochemical characterization of two chromatin fractions isolated by ECTHAM-cellulose chromatography.", "content": "Chromatin prepared at various stages of hormone-mediated development of the chick oviduct was investigated for the relative proportions of transcriptionally active (fraction I) and repressed (fraction II) fractions by ECTHAM-cellulose chromatography. During primary stimulation with estrogen, the amount of chromatin DNA in fraction I plotted as a function of time of stimulation showed a bell-shaped profile, similar to the profile obtained earlier for the number of chromatin sites available to RNA polymerase for initiation of RNA synthesis. Chromatin form a transcriptionally inactive system, hen erythrocytes, eluted mainly (98%) as fraction II. The transcriptionally active fraction I of estrogen-stimulated oviduct contained a 4-fold greater RNA polymerase II activity than was found in fraction II. This could be explained by a differential inhibition of RNA polymerase activity in fraction II since enzyme preparations extracted and purified from both chromatin fractions showed equal activities. In support of this finding, fraction I eluted from ECTHAM-cellulose showed a 4-fold greater concentration of rifampicin-resistant RNA chain initiation sites as compared to fraction II. When chromatin from oviduct mince incubated with labeled progesterone and 17 beta-estradiol and was chromatographed on ECTHAM-cellulose, the transcriptionally active fraction also contained a 4-fold greater concentration of bound hormone (per weight DNA) as compared to the repressed fraction.", "contents": "Studies on the structure and function of chick-oviduct chromatin. 2. Biochemical characterization of two chromatin fractions isolated by ECTHAM-cellulose chromatography. Chromatin prepared at various stages of hormone-mediated development of the chick oviduct was investigated for the relative proportions of transcriptionally active (fraction I) and repressed (fraction II) fractions by ECTHAM-cellulose chromatography. During primary stimulation with estrogen, the amount of chromatin DNA in fraction I plotted as a function of time of stimulation showed a bell-shaped profile, similar to the profile obtained earlier for the number of chromatin sites available to RNA polymerase for initiation of RNA synthesis. Chromatin form a transcriptionally inactive system, hen erythrocytes, eluted mainly (98%) as fraction II. The transcriptionally active fraction I of estrogen-stimulated oviduct contained a 4-fold greater RNA polymerase II activity than was found in fraction II. This could be explained by a differential inhibition of RNA polymerase activity in fraction II since enzyme preparations extracted and purified from both chromatin fractions showed equal activities. In support of this finding, fraction I eluted from ECTHAM-cellulose showed a 4-fold greater concentration of rifampicin-resistant RNA chain initiation sites as compared to fraction II. When chromatin from oviduct mince incubated with labeled progesterone and 17 beta-estradiol and was chromatographed on ECTHAM-cellulose, the transcriptionally active fraction also contained a 4-fold greater concentration of bound hormone (per weight DNA) as compared to the repressed fraction."} {"id": "PMID:182492", "title": "Activity and subcellular distribution of protein kinase dependent on adenosine 3':5'-monophosphate in liver from normal and adrenalectomized rats.", "content": "We have examined whether glucocorticoids control the activity and (or) the subcellular distribution of protein kinase dependent on cyclic AMP (adenosine 3':5'-monophosphate), since they influence cyclic-AMP-dependent responses to other hormones. Protein kinase activity was determined in rat liver homogenates and subcellular fractions, nuclear, large granular, microsomal and supernatant obtained by differential sedimentation in 0.25 M sucrose. 63% of the tissue protein kinase activity detected in absence of cyclic AMP reside in the particulate fractions. Upon addition of exogenous cyclic AMP, protein kinase activity is stimulated 1.8, 1.2, 1.2 and 4.5-fold in nuclear, large granular, microsomal and supernatant fractions, respectively. Under these conditions, 66% of tissue activity are found in the supernatant fraction. The activity sensitive to exogenous cyclic AMP resolves into a major (84%) cytosoluble and a minor (16%) nucleomicrosomal component. The latter activity resists elution with isotonic saline and is increased in the presence of Triton X-100. Three groups of rats were studied: control and adrenalectomized with or without cortisol treatment. In whole liver homogenates, both protein kinase activity detected in absence of exogenous cyclic AMP and sensitivity of the enzyme to cyclic AMP were comparable in all groups. Moreover, the distribution patterns of proteins kinase activity amoung the fractions were essentially the same in all groups of animals, whether or not particles had been treated with Triton X-100. Finally, in cell-free experiments, glucocorticoids alone or in combination with their intracellular receptor did not modify protein kinase activity of rat liver. Thus the results reported do not support the possibility that glucocorticoids influence cyclic AMP-dependent protein kinase in rat liver. Yet, this study provides data, not available before, on subcellular distribution of this enzyme in rat liver.", "contents": "Activity and subcellular distribution of protein kinase dependent on adenosine 3':5'-monophosphate in liver from normal and adrenalectomized rats. We have examined whether glucocorticoids control the activity and (or) the subcellular distribution of protein kinase dependent on cyclic AMP (adenosine 3':5'-monophosphate), since they influence cyclic-AMP-dependent responses to other hormones. Protein kinase activity was determined in rat liver homogenates and subcellular fractions, nuclear, large granular, microsomal and supernatant obtained by differential sedimentation in 0.25 M sucrose. 63% of the tissue protein kinase activity detected in absence of cyclic AMP reside in the particulate fractions. Upon addition of exogenous cyclic AMP, protein kinase activity is stimulated 1.8, 1.2, 1.2 and 4.5-fold in nuclear, large granular, microsomal and supernatant fractions, respectively. Under these conditions, 66% of tissue activity are found in the supernatant fraction. The activity sensitive to exogenous cyclic AMP resolves into a major (84%) cytosoluble and a minor (16%) nucleomicrosomal component. The latter activity resists elution with isotonic saline and is increased in the presence of Triton X-100. Three groups of rats were studied: control and adrenalectomized with or without cortisol treatment. In whole liver homogenates, both protein kinase activity detected in absence of exogenous cyclic AMP and sensitivity of the enzyme to cyclic AMP were comparable in all groups. Moreover, the distribution patterns of proteins kinase activity amoung the fractions were essentially the same in all groups of animals, whether or not particles had been treated with Triton X-100. Finally, in cell-free experiments, glucocorticoids alone or in combination with their intracellular receptor did not modify protein kinase activity of rat liver. Thus the results reported do not support the possibility that glucocorticoids influence cyclic AMP-dependent protein kinase in rat liver. Yet, this study provides data, not available before, on subcellular distribution of this enzyme in rat liver."} {"id": "PMID:182493", "title": "Multifunctional enzyme, bisphosphoglyceromutase/2,3-bisphosphoglycerate phosphatase/phosphoglyceromutase, from human erythrocytes. Evidence for a common active site.", "content": "Bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities responsible for 2,3-bisphosphoglycerate metabolsim in human red cells are displayed by the same enzyme protein which has phosphoglyceromutase activity [Sasaki, R., et al. (1975) Eur J. Biochem. 50, 581-593]. This enzyme was subjected to chemical modification by trinitrobenzenesulfonate. The three enzyme activities were inactivated by trinitrobenzenesulfonate at the same rate. The sulfhydryl content of the enzyme was unchanged during trinitrophenylation, indicating that derivatization was through the amino group. Trinitrophenylation of about one amino group per mole of the enzyme resulted in complete loss of the three activities. Both 2,3-bisphosphoglycerate and 1,3-bisphosphoglycerate inhibited trinitrophenylation and effectively protected the enzyme from inactivation. Although monophosphoglycerates did not show any protective effect at concentrations which should be adequate based upon their kinetic constants, they were protective at higher concentrations. Inactivation by trinitrophenylation was an apparent first-order reaction. The dissociation constant of the enzyme - 2,3-bisphosphoglycerate complex was determined by analyzing the first-order reaction on the assumption that the protective effect of 2,3-bisphosphoglycerate was due to competition with trinitrobenzenesulfonate. The dissociation constant was in good agreement with kinetic constants of 2,3-bisphosphoglycerate in the enzyme reactions, which indicated that 2,3-bisphosphoglycerate did indeed exert its protective effect through competition with trinitrobenzenesulfonate for an amino group of the enzyme. The protective effect of monophosphoglycerates could be rationalized with kinetic evidence that 2-phosphoglycerate at high concentrations interacts with the 2,3-bisphosphoglycerate binding site. These results indicate that the enzyme exhibits the three enzyme activities at a common active site at which one amino group essential for binding of bisphosphoglycerates is located. Based on the multifunctional properties of this enzyme, a possible mechanism was discussed for regulation of 2,3-bisphosphoglycerate metabolism in human red cells.", "contents": "Multifunctional enzyme, bisphosphoglyceromutase/2,3-bisphosphoglycerate phosphatase/phosphoglyceromutase, from human erythrocytes. Evidence for a common active site. Bisphosphoglyceromutase and 2,3-bisphosphoglycerate phosphatase activities responsible for 2,3-bisphosphoglycerate metabolsim in human red cells are displayed by the same enzyme protein which has phosphoglyceromutase activity [Sasaki, R., et al. (1975) Eur J. Biochem. 50, 581-593]. This enzyme was subjected to chemical modification by trinitrobenzenesulfonate. The three enzyme activities were inactivated by trinitrobenzenesulfonate at the same rate. The sulfhydryl content of the enzyme was unchanged during trinitrophenylation, indicating that derivatization was through the amino group. Trinitrophenylation of about one amino group per mole of the enzyme resulted in complete loss of the three activities. Both 2,3-bisphosphoglycerate and 1,3-bisphosphoglycerate inhibited trinitrophenylation and effectively protected the enzyme from inactivation. Although monophosphoglycerates did not show any protective effect at concentrations which should be adequate based upon their kinetic constants, they were protective at higher concentrations. Inactivation by trinitrophenylation was an apparent first-order reaction. The dissociation constant of the enzyme - 2,3-bisphosphoglycerate complex was determined by analyzing the first-order reaction on the assumption that the protective effect of 2,3-bisphosphoglycerate was due to competition with trinitrobenzenesulfonate. The dissociation constant was in good agreement with kinetic constants of 2,3-bisphosphoglycerate in the enzyme reactions, which indicated that 2,3-bisphosphoglycerate did indeed exert its protective effect through competition with trinitrobenzenesulfonate for an amino group of the enzyme. The protective effect of monophosphoglycerates could be rationalized with kinetic evidence that 2-phosphoglycerate at high concentrations interacts with the 2,3-bisphosphoglycerate binding site. These results indicate that the enzyme exhibits the three enzyme activities at a common active site at which one amino group essential for binding of bisphosphoglycerates is located. Based on the multifunctional properties of this enzyme, a possible mechanism was discussed for regulation of 2,3-bisphosphoglycerate metabolism in human red cells."} {"id": "PMID:182494", "title": "Subunit structure and multifunctional properties of yeast phosphoglyceromutase.", "content": "1. A new and efficient method for preparation of pure phosphoglyceromutase from baker's yeast (Saccharomyces cerevisiae) is described. Proteolytic alterations of the enzyme during extraction can be minimized by grinding the dried yeast with aluminium oxide at low temperature. 2. Yeast phosphoglyceromutase contains four highly similar, probably idential subunits of molecular weight 28000, a conclusion based on the following observations. Polyacrylamide gel electrophoresis containing dodecylsulphate or urea gives a single band, indicating that the enzyme is composed of four subunits similar in their molecular weight and net charge. Cyanogen bromide cleavage and tryptic digestion of the enzyme yield the number of peptides expected for identical subunites from the amino acid composition analysis. 3. The purified phosphoglyceromutase preparation has bisphosphoglyceromutase activity synthesizing 2,3-bisphosphoglycerate from 1,3-bisphosphoglycerate and 3-phosphoglycerate. It has been reported that yeast phosphoglyceromutase catalyzes the hydrolysis of 2,3-bisphosphoglycerate at the same active site which catalyzes the phosphoglyceromutase reaction [Sasaki, R. et al (1971) Biochim. Biophys, Acta, 227, 584-594, 595-607]. Immunological studies and chemical modification experiments indicate that bisphosphoglyceromutase activity also is due to the phosphoglyceromutase protein and involves amino groups which have been shown to be essential for the other two activities.", "contents": "Subunit structure and multifunctional properties of yeast phosphoglyceromutase. 1. A new and efficient method for preparation of pure phosphoglyceromutase from baker's yeast (Saccharomyces cerevisiae) is described. Proteolytic alterations of the enzyme during extraction can be minimized by grinding the dried yeast with aluminium oxide at low temperature. 2. Yeast phosphoglyceromutase contains four highly similar, probably idential subunits of molecular weight 28000, a conclusion based on the following observations. Polyacrylamide gel electrophoresis containing dodecylsulphate or urea gives a single band, indicating that the enzyme is composed of four subunits similar in their molecular weight and net charge. Cyanogen bromide cleavage and tryptic digestion of the enzyme yield the number of peptides expected for identical subunites from the amino acid composition analysis. 3. The purified phosphoglyceromutase preparation has bisphosphoglyceromutase activity synthesizing 2,3-bisphosphoglycerate from 1,3-bisphosphoglycerate and 3-phosphoglycerate. It has been reported that yeast phosphoglyceromutase catalyzes the hydrolysis of 2,3-bisphosphoglycerate at the same active site which catalyzes the phosphoglyceromutase reaction [Sasaki, R. et al (1971) Biochim. Biophys, Acta, 227, 584-594, 595-607]. Immunological studies and chemical modification experiments indicate that bisphosphoglyceromutase activity also is due to the phosphoglyceromutase protein and involves amino groups which have been shown to be essential for the other two activities."} {"id": "PMID:182495", "title": "Developmental changes in prolyl hydroxylase activity and protein in chick embryo.", "content": "Changes in prolyl hydroxylase activity and immunoreactive protein were studied in various chick embryo tissues during the embryonic development. Both the enzyme activity and the amoung of immunoreactive protein increased till the 16th day of development and declined thereafter in all tissues studied. Comparison of the enzyme activity to the content of the total immuno-reactive protein indicated that there are distinct differences in the degree of enzyme activity between different chick embryo tissues, and in the same tissue between different stages of embryonic development. The highest relative enzyme activities were found in cartilage and skin, in which about 60% of the enzyme was active on the 16th day of development and only 20-30% was active on the 20th day of development; the lowest values were observed in spleen and large vessels, in which below 10% of the enzyme protein was in the active form on the 20th day of development Gel filtration studies demonstrated that in cartilage of 16-day-old chick embryos about 60% of the total immunoreactive enzyme in the tissue was present in the form of active prolylhydroxylase tetramer, whereas on the 20th day of development only 30% of the enzyme protein in cartilage was in the tetramer form. By contrast, in large vessels of the 16-day-old chick embryos, essentially all the enzyme was in the form of prolyl hydroxylase monomers.", "contents": "Developmental changes in prolyl hydroxylase activity and protein in chick embryo. Changes in prolyl hydroxylase activity and immunoreactive protein were studied in various chick embryo tissues during the embryonic development. Both the enzyme activity and the amoung of immunoreactive protein increased till the 16th day of development and declined thereafter in all tissues studied. Comparison of the enzyme activity to the content of the total immuno-reactive protein indicated that there are distinct differences in the degree of enzyme activity between different chick embryo tissues, and in the same tissue between different stages of embryonic development. The highest relative enzyme activities were found in cartilage and skin, in which about 60% of the enzyme was active on the 16th day of development and only 20-30% was active on the 20th day of development; the lowest values were observed in spleen and large vessels, in which below 10% of the enzyme protein was in the active form on the 20th day of development Gel filtration studies demonstrated that in cartilage of 16-day-old chick embryos about 60% of the total immunoreactive enzyme in the tissue was present in the form of active prolylhydroxylase tetramer, whereas on the 20th day of development only 30% of the enzyme protein in cartilage was in the tetramer form. By contrast, in large vessels of the 16-day-old chick embryos, essentially all the enzyme was in the form of prolyl hydroxylase monomers."} {"id": "PMID:182496", "title": "Intermittent cerebral symptoms in type V hyperlipoproteinemia.", "content": "A case with central nervous symptoms in type V hyperlipoproteinemia was described. The 39-year-old male patient suffered from abdominal pains after fatty meals since childhood. After the age of 31 he developed attacks of cephaleas. Headaches were associated with vertigo, paresis and paresthesia of the limbs and loss of consciousness in some instances. During antilipemic treatment combined with a diet of restricted fat and carbohydrate content the patient became free of complaints. Authors emphasize the impairment of cerebral circulation and tissue hypoxia in the development of cerebral disturbances in hyperlipoproteinemia. The mechanism of the development of hypoxia is discussed.", "contents": "Intermittent cerebral symptoms in type V hyperlipoproteinemia. A case with central nervous symptoms in type V hyperlipoproteinemia was described. The 39-year-old male patient suffered from abdominal pains after fatty meals since childhood. After the age of 31 he developed attacks of cephaleas. Headaches were associated with vertigo, paresis and paresthesia of the limbs and loss of consciousness in some instances. During antilipemic treatment combined with a diet of restricted fat and carbohydrate content the patient became free of complaints. Authors emphasize the impairment of cerebral circulation and tissue hypoxia in the development of cerebral disturbances in hyperlipoproteinemia. The mechanism of the development of hypoxia is discussed."} {"id": "PMID:182497", "title": "Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria.", "content": "The influence of long-term corticosteroid and ACTH therapy in two sisters was followed up. The periods of observation were 4 and 2 years. The high levels of corticosteroids obviously reversed the fatal progress of the disease. The relapses in the elder sister occurred during longer periods of discontinued corticosteroid therapy. In the younger the therapy was continuous. There was no relapse except for a short one appearing after the tooth extraction and discontinuation of the therapy for 10 days. Some correlation between neurological signs and symptoms and porphobilinogen androporphyrin levels were found. The question arises how it is possible to influence the genetically determined disease by corticosteroids or ACTH.", "contents": "Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria. The influence of long-term corticosteroid and ACTH therapy in two sisters was followed up. The periods of observation were 4 and 2 years. The high levels of corticosteroids obviously reversed the fatal progress of the disease. The relapses in the elder sister occurred during longer periods of discontinued corticosteroid therapy. In the younger the therapy was continuous. There was no relapse except for a short one appearing after the tooth extraction and discontinuation of the therapy for 10 days. Some correlation between neurological signs and symptoms and porphobilinogen androporphyrin levels were found. The question arises how it is possible to influence the genetically determined disease by corticosteroids or ACTH."} {"id": "PMID:182501", "title": "Turnover of plasma cholesteryl esters and its relationship to other parameters of lipid metabolism in man.", "content": "Studies on plasma cholesteryl esters were made in 32 normal and hyperlipidaemic subjects in an attempt to elucidate further the metabolic relationships between cholesterol and other plasma lipids and lipoproteins. Fractional and net turnover rates of plasma cholesteryl esters were measured using two independent (in vivo and in vitro) methods, both of which determined the prevailing activity of plasma lecithin: cholesterol acyltransferase in the ambiance of the patients own plasma. The results obtained by the two methods were in excellent agreement. The turnover rates of plasma cholesteryl esters in hypertriglyceridaemic patients were significantly greater than in patients with only hypercholesterolaemia and in those with normal plasma lipids. In agreement with these observations, the esterified to free cholesterol ratios in hypertriglyceridaemic patients were significantly greater than in those with normal plasma triglycerides. Patients who had only hypercholesterolaemia had normal esterified to free cholesterol ratios. The rates of esterification of plasma free cholesterol correlated well with triglyceride concentrations as well as with the net turnover of plasma triglycerides and also with the turnover or synthesis of endogenous cholesterol. Since the turnover of plasma triglycerides in most patients with modest to moderate hypertriglyceridaemia reflects the turnover of their plasma very low density lipoproteins, it is suggested that it is the turnover of these lipoproteins which correlates with the hepatic synthesis of cholesterol and with the esterification of plasma cholesteryl esters.", "contents": "Turnover of plasma cholesteryl esters and its relationship to other parameters of lipid metabolism in man. Studies on plasma cholesteryl esters were made in 32 normal and hyperlipidaemic subjects in an attempt to elucidate further the metabolic relationships between cholesterol and other plasma lipids and lipoproteins. Fractional and net turnover rates of plasma cholesteryl esters were measured using two independent (in vivo and in vitro) methods, both of which determined the prevailing activity of plasma lecithin: cholesterol acyltransferase in the ambiance of the patients own plasma. The results obtained by the two methods were in excellent agreement. The turnover rates of plasma cholesteryl esters in hypertriglyceridaemic patients were significantly greater than in patients with only hypercholesterolaemia and in those with normal plasma lipids. In agreement with these observations, the esterified to free cholesterol ratios in hypertriglyceridaemic patients were significantly greater than in those with normal plasma triglycerides. Patients who had only hypercholesterolaemia had normal esterified to free cholesterol ratios. The rates of esterification of plasma free cholesterol correlated well with triglyceride concentrations as well as with the net turnover of plasma triglycerides and also with the turnover or synthesis of endogenous cholesterol. Since the turnover of plasma triglycerides in most patients with modest to moderate hypertriglyceridaemia reflects the turnover of their plasma very low density lipoproteins, it is suggested that it is the turnover of these lipoproteins which correlates with the hepatic synthesis of cholesterol and with the esterification of plasma cholesteryl esters."} {"id": "PMID:182502", "title": "Electron microscopic characterization of lipoproteins from patients with familial type III hyperlipoproteinaemia.", "content": "The lipoproteins of very low density, low density and intermediate density were isolated by zonal ultracentrifugation from the plasma of subjects with familial type III hyperlipoproteinaemia and studied by electron microscopy. Each of these lipoproteins exhibited a spherical shape when free-standing. The very low density, low density and intermediate density lipoproteins ranged in diameter from 31 - 80, 17 - 23, .and 21 - 35 nm, respectively. These results are consistent with our previous findings that the intermediate density lipoprotein particles characteristic of plasma from type III subjects exhibit properties which are intermediate between those of very low density and low density lipoproteins.", "contents": "Electron microscopic characterization of lipoproteins from patients with familial type III hyperlipoproteinaemia. The lipoproteins of very low density, low density and intermediate density were isolated by zonal ultracentrifugation from the plasma of subjects with familial type III hyperlipoproteinaemia and studied by electron microscopy. Each of these lipoproteins exhibited a spherical shape when free-standing. The very low density, low density and intermediate density lipoproteins ranged in diameter from 31 - 80, 17 - 23, .and 21 - 35 nm, respectively. These results are consistent with our previous findings that the intermediate density lipoprotein particles characteristic of plasma from type III subjects exhibit properties which are intermediate between those of very low density and low density lipoproteins."} {"id": "PMID:182503", "title": "The antagonism of nicotine-induced cardiovascular responses by DMAE and DEO analogs.", "content": "A series of quaternary ammonium compounds cinsisting of 4, 4'-bis-[N-(2, 2-diethoxyethyl)-N, N-dimethylammonioacetyl]-biphenyl dibromide (DMAE) and 4, 4'-bis-[N, N-di(2-ethoxyethyl)-N-methylammonioacetyl]-biphenyl dibromide (DEO) analogs was investigated for selective nicotine antagonism. Each series of compounds contained the monophenyl (MPh.DMAE, MPh.DEO); biphenyl (DMAE, DEO); terphenyl (TPh,DMAE, TPh.DEO); half-molecule (1/2DMAE, 1/2DEO); p-phenyl half-molecule (p-Ph.-1/2DMAE, p-Ph.-1/2DEO) and biphenyl half-molecule (p-BPh.-1/2DMAE, p-BPh.-1/2DEO) analogs. Studies were conducted on isolated spontaneously beating guinea pig atria and anesthetized dogs. Relative potencies of the DMAE and DEO series to antagonize the nicotine (20 mug/ml) induced positive chronotropic effect of the guinea pig atria were determined as follows: DMAE (1.0); TPh.DMAE (0.82); P-Ph.1/2DMAE (0.59); DEO (0.54); MPh.DMAE (0.27); TPh.DEO (0.26); MPh.DEO (0.18); p-Ph.-1/2DEO (0.16); 1/2DMAE (0.03); 1/2DEO (0.02); p-BPh.-1/2DMAE (less than 0.01); p-BPh.-1/2DEO (less than 0.01) and C-6 (0.85). The I50 to antagonize nicotine induced responses by DMAE was 0.13 muM (0.10 mu/ml). Several of the above analogs were studied in the dog and their ability to antagonize nicotine (100 mug/kg) induced positive chronotropic effects were compared with their ability to inhibit transmission through the stellate or the superior cervical ganglia. The I50 doses of the drugs antagonizing nicotine, impairing superior cervical ganglionic transmission and the corresponding fold shifts in the dose--response curves follow: DMAE (120 mug/kg, 3.0 mg/kg, 25); TPh.DMAE (40 mug/kg, 1.10 mg/kg, 30), DEO (45 mug/kg, 1.30 mg/kg, 25) and C-6 (140 mug/kg, 0.42 mg/kg, 0.42 mg/kg, 3.0). These findings are suggestive of the hypothesis that receptors normally activated by endogenously released ACh in the stellate or superior cervical ganglia of the dog may be dissociated from those receptors activated by nicotine which results in an increase in blood pressure or heart rate. Clinical implications are that TPh.DMAE as well as other DMAE analogs may pose less of a problem with hypotension than hexamethonium as a nicotine antagonist.", "contents": "The antagonism of nicotine-induced cardiovascular responses by DMAE and DEO analogs. A series of quaternary ammonium compounds cinsisting of 4, 4'-bis-[N-(2, 2-diethoxyethyl)-N, N-dimethylammonioacetyl]-biphenyl dibromide (DMAE) and 4, 4'-bis-[N, N-di(2-ethoxyethyl)-N-methylammonioacetyl]-biphenyl dibromide (DEO) analogs was investigated for selective nicotine antagonism. Each series of compounds contained the monophenyl (MPh.DMAE, MPh.DEO); biphenyl (DMAE, DEO); terphenyl (TPh,DMAE, TPh.DEO); half-molecule (1/2DMAE, 1/2DEO); p-phenyl half-molecule (p-Ph.-1/2DMAE, p-Ph.-1/2DEO) and biphenyl half-molecule (p-BPh.-1/2DMAE, p-BPh.-1/2DEO) analogs. Studies were conducted on isolated spontaneously beating guinea pig atria and anesthetized dogs. Relative potencies of the DMAE and DEO series to antagonize the nicotine (20 mug/ml) induced positive chronotropic effect of the guinea pig atria were determined as follows: DMAE (1.0); TPh.DMAE (0.82); P-Ph.1/2DMAE (0.59); DEO (0.54); MPh.DMAE (0.27); TPh.DEO (0.26); MPh.DEO (0.18); p-Ph.-1/2DEO (0.16); 1/2DMAE (0.03); 1/2DEO (0.02); p-BPh.-1/2DMAE (less than 0.01); p-BPh.-1/2DEO (less than 0.01) and C-6 (0.85). The I50 to antagonize nicotine induced responses by DMAE was 0.13 muM (0.10 mu/ml). Several of the above analogs were studied in the dog and their ability to antagonize nicotine (100 mug/kg) induced positive chronotropic effects were compared with their ability to inhibit transmission through the stellate or the superior cervical ganglia. The I50 doses of the drugs antagonizing nicotine, impairing superior cervical ganglionic transmission and the corresponding fold shifts in the dose--response curves follow: DMAE (120 mug/kg, 3.0 mg/kg, 25); TPh.DMAE (40 mug/kg, 1.10 mg/kg, 30), DEO (45 mug/kg, 1.30 mg/kg, 25) and C-6 (140 mug/kg, 0.42 mg/kg, 0.42 mg/kg, 3.0). These findings are suggestive of the hypothesis that receptors normally activated by endogenously released ACh in the stellate or superior cervical ganglia of the dog may be dissociated from those receptors activated by nicotine which results in an increase in blood pressure or heart rate. Clinical implications are that TPh.DMAE as well as other DMAE analogs may pose less of a problem with hypotension than hexamethonium as a nicotine antagonist."} {"id": "PMID:182504", "title": "Effect of a cholinergic stimulant on interaction of isoprenaline with beta-adrenoceptors.", "content": "The maximum contraction induced in taenia from the guninea pig caecum by a cholinergic stimulant, butyltrimethylammonium (BuTMA) was relaxed by papaverine (10(-4) M) but not by l-isoprenaline (5 X 10(-7) M). The concentrations used relaxed the taenia completely in the absence of BuTMA. BuTMA (10(-4) M) decreased the increase of cyclic AMP caused by isoprenaline but not that due to papaverine. Futhermore, photoinactivation of the beta-adrenoceptors by l-isoprenaline was not observed on the taenia contracted by BuTMA (10(-4) M). These results suggest that l-isoprenaline does nto interact with the beta-adrenoceptors in the taenie contracted by the high concentration of BuTMA.", "contents": "Effect of a cholinergic stimulant on interaction of isoprenaline with beta-adrenoceptors. The maximum contraction induced in taenia from the guninea pig caecum by a cholinergic stimulant, butyltrimethylammonium (BuTMA) was relaxed by papaverine (10(-4) M) but not by l-isoprenaline (5 X 10(-7) M). The concentrations used relaxed the taenia completely in the absence of BuTMA. BuTMA (10(-4) M) decreased the increase of cyclic AMP caused by isoprenaline but not that due to papaverine. Futhermore, photoinactivation of the beta-adrenoceptors by l-isoprenaline was not observed on the taenia contracted by BuTMA (10(-4) M). These results suggest that l-isoprenaline does nto interact with the beta-adrenoceptors in the taenie contracted by the high concentration of BuTMA."} {"id": "PMID:182505", "title": "Effects of neuroleptic agents on cyclic GMP in rat cerebral cortex.", "content": "Cyclic guanosine 3' ,5'-monophosphate(cyclic GMP) levels were increased in incubated tissue slices from rat cerebral cortex in response to added cholinomimetic agents (carbachol and choline chloride) and neuroleptic compounds (chlorpromazine, 8-hydroxychlorpromazine, 7-hydroxychlorpromazine methiodide, haloperidol, thioridazine, chlorpromazine sulfoxide and promethazine). Calcium ion was required for this effect. Moreover, selected agents namely, 7,8-dihydroxychlorpromazine, 7,8-dimethoxychlorpromazine, chlorpromazine and clozapine prevented the rise in cyclic GMP induced by carbachol.", "contents": "Effects of neuroleptic agents on cyclic GMP in rat cerebral cortex. Cyclic guanosine 3' ,5'-monophosphate(cyclic GMP) levels were increased in incubated tissue slices from rat cerebral cortex in response to added cholinomimetic agents (carbachol and choline chloride) and neuroleptic compounds (chlorpromazine, 8-hydroxychlorpromazine, 7-hydroxychlorpromazine methiodide, haloperidol, thioridazine, chlorpromazine sulfoxide and promethazine). Calcium ion was required for this effect. Moreover, selected agents namely, 7,8-dihydroxychlorpromazine, 7,8-dimethoxychlorpromazine, chlorpromazine and clozapine prevented the rise in cyclic GMP induced by carbachol."} {"id": "PMID:182506", "title": "Somatostatin and ACTH are peptides with partial antagonist-like selectivity for opiate receptors.", "content": "The peptides, Met-enkephalin and somatostatin were analysed for competitive affinity to opiate agonist receptor sites in rat brain. Met-enkephalin, like morphinomimetic compounds, being equal to marked selectivity for agonist sites while somatostatin and ACTH showed much less selectivity, being equal to partial antagonists like nalorphine. These results are compared with those observed for these peptides in vivo. It is suggested that somatostatin and acth act as partial agonist--antagonist on opiate receptors in the cns.", "contents": "Somatostatin and ACTH are peptides with partial antagonist-like selectivity for opiate receptors. The peptides, Met-enkephalin and somatostatin were analysed for competitive affinity to opiate agonist receptor sites in rat brain. Met-enkephalin, like morphinomimetic compounds, being equal to marked selectivity for agonist sites while somatostatin and ACTH showed much less selectivity, being equal to partial antagonists like nalorphine. These results are compared with those observed for these peptides in vivo. It is suggested that somatostatin and acth act as partial agonist--antagonist on opiate receptors in the cns."} {"id": "PMID:182507", "title": "Effect of some phosphodiesterase inhibitors on central dopamine mechanisms.", "content": "The effect of five phosphodiesterase (PDE) inhibitors (papaverine, IBMX, theophyllamine, dipyridamol and M & B 22,948) was studied on adenylate cyclase and on cyclic nucleotide phosphodiesterase activities in extracts of rat caudate nucleus. For comparison the effect on DA turnover and on turning behaviour in rats with unilateral lesions of the nigro-neostriatal DA nerurons was studied. Cyclic AMP PDE was inhibited by papaverine, dipyridamol, IBMX, M & B 22,948 and theophyllamine in that order of potency. Cylcic GMP PDE was inhibited by IBMX, papaverine, M & B 22,948 and theophyllamine, but not by dipyridamol. Basal adenylate cyclase washigher if assayed in the presence of papaverine or dipyridamol than if theophyllamine or IBMX was present. The degree of stimulation caused by DA was not significantly influenced by the PDE inhibitors. Papaverine and dipyridamol enhanced DA disappearance in the caudate nucleus and the tuberculum accumbens, but not in the median eminence. Caffeine had no significant effect. Papaverine (1-28 mg/kg) had no signigicant effect on L-dopa (5 mg/kg)-induced turning, and actually inhibited turning induced by the combination of L-dopa (10 mg/kg) and atropine (5 mg/kg). The other four PDE inhibitors all potentiated L-dopa-induced turning. Theophyllamine (20 mg/kg) and IBMX (5 mg/kg) even caused turning when given alone. The data are compatible with the opinion that PDE inhibition leads to an enhanced effect of DA in the caudate nucleus. However, the results also demonstrate that several of the PDE inhibitors have effects on central DA mechanisms that are difficult to explain solely on the basis of PED inhibition.", "contents": "Effect of some phosphodiesterase inhibitors on central dopamine mechanisms. The effect of five phosphodiesterase (PDE) inhibitors (papaverine, IBMX, theophyllamine, dipyridamol and M & B 22,948) was studied on adenylate cyclase and on cyclic nucleotide phosphodiesterase activities in extracts of rat caudate nucleus. For comparison the effect on DA turnover and on turning behaviour in rats with unilateral lesions of the nigro-neostriatal DA nerurons was studied. Cyclic AMP PDE was inhibited by papaverine, dipyridamol, IBMX, M & B 22,948 and theophyllamine in that order of potency. Cylcic GMP PDE was inhibited by IBMX, papaverine, M & B 22,948 and theophyllamine, but not by dipyridamol. Basal adenylate cyclase washigher if assayed in the presence of papaverine or dipyridamol than if theophyllamine or IBMX was present. The degree of stimulation caused by DA was not significantly influenced by the PDE inhibitors. Papaverine and dipyridamol enhanced DA disappearance in the caudate nucleus and the tuberculum accumbens, but not in the median eminence. Caffeine had no significant effect. Papaverine (1-28 mg/kg) had no signigicant effect on L-dopa (5 mg/kg)-induced turning, and actually inhibited turning induced by the combination of L-dopa (10 mg/kg) and atropine (5 mg/kg). The other four PDE inhibitors all potentiated L-dopa-induced turning. Theophyllamine (20 mg/kg) and IBMX (5 mg/kg) even caused turning when given alone. The data are compatible with the opinion that PDE inhibition leads to an enhanced effect of DA in the caudate nucleus. However, the results also demonstrate that several of the PDE inhibitors have effects on central DA mechanisms that are difficult to explain solely on the basis of PED inhibition."} {"id": "PMID:182508", "title": "The potentiating effects of 4-aminopyridine on adrenergic transmission in the rabbit vas deferens.", "content": "The effects of 4-aminipyridine on adrenergic transmission in rabbit vas deferens were investigated. 10(-5)-10(-3) M 4-aminopyridine markedly potentiated the sustained, secondary contractile response to transmural stimulation and significantly increased the amount of (+/-)-|3H]-metaraminol released at 5 Hz, but had little effect on responses to exogenous (-)-noradrenaline. 10(-5)-10(-4) M 4-aminopyridine did not significantly alter the accumulation or efflux of (-)-[3H]-noradrenaline in rabbit heart. It is suggested that 4-aminopyridine potentiated responses of rabbit vas deferens to transmural stimulation mainly by increasing transmitter release, possibly as a result of prolongation of the action potential. Responses to transmural stimulation were also potentiated by by 2- and 3-aminopyridine and by 3,4-diaminopyridine but not by pyridine, aniline, 4-dimethylaminopyridine, 4-aminoethylpyridine or 2-aminopyrimidine.", "contents": "The potentiating effects of 4-aminopyridine on adrenergic transmission in the rabbit vas deferens. The effects of 4-aminipyridine on adrenergic transmission in rabbit vas deferens were investigated. 10(-5)-10(-3) M 4-aminopyridine markedly potentiated the sustained, secondary contractile response to transmural stimulation and significantly increased the amount of (+/-)-|3H]-metaraminol released at 5 Hz, but had little effect on responses to exogenous (-)-noradrenaline. 10(-5)-10(-4) M 4-aminopyridine did not significantly alter the accumulation or efflux of (-)-[3H]-noradrenaline in rabbit heart. It is suggested that 4-aminopyridine potentiated responses of rabbit vas deferens to transmural stimulation mainly by increasing transmitter release, possibly as a result of prolongation of the action potential. Responses to transmural stimulation were also potentiated by by 2- and 3-aminopyridine and by 3,4-diaminopyridine but not by pyridine, aniline, 4-dimethylaminopyridine, 4-aminoethylpyridine or 2-aminopyrimidine."} {"id": "PMID:182509", "title": "Effects of ethanol on the cyclic AMP system of the dog gastric mucosa.", "content": "The effect of ethanol on the cyclic AMP system of the dog fundic mucosa was studied in vitro. The gastric mucosal content of cyclic AMP was increased by 2.5% ethanol, whereas 10 and 20% ethanol decreased the mucosal content of cyclic AMP. The activity of adenylate cyclase was increased by 2.5 and 5% ethanol, whereas 10% ethanol did not significantly affect it. The activity of cyclic AMP phosphodiesterase was inhibited by ethanol in a competitive manner. The increase in the gastric mucosal content of cyclic AMP, induced by low concentrations of ethanol, is apparently due to the stimulation of adenylate cyclase and inhibition of phosphodiesterase. Changes in the phosphodiesterase or adenylate cyclase activites do not explain the decrease of the mucosal content of cyclic AMP by higher concentrations of ethanol. The mechanism of the decrease is discussed.", "contents": "Effects of ethanol on the cyclic AMP system of the dog gastric mucosa. The effect of ethanol on the cyclic AMP system of the dog fundic mucosa was studied in vitro. The gastric mucosal content of cyclic AMP was increased by 2.5% ethanol, whereas 10 and 20% ethanol decreased the mucosal content of cyclic AMP. The activity of adenylate cyclase was increased by 2.5 and 5% ethanol, whereas 10% ethanol did not significantly affect it. The activity of cyclic AMP phosphodiesterase was inhibited by ethanol in a competitive manner. The increase in the gastric mucosal content of cyclic AMP, induced by low concentrations of ethanol, is apparently due to the stimulation of adenylate cyclase and inhibition of phosphodiesterase. Changes in the phosphodiesterase or adenylate cyclase activites do not explain the decrease of the mucosal content of cyclic AMP by higher concentrations of ethanol. The mechanism of the decrease is discussed."} {"id": "PMID:182510", "title": "Brain dopamine receptors and sleep in the rat: effects of stimulation and blockade.", "content": "A high dose of apomorphine, a stimulator of brain dopamine receptors, caused a reduction in total sleep, intermediate sleep and a delayed appearance of paradoxical sleep. With a lower dose, a small and not significant trend toward an increase of paradoxical sleep was observed. Spiroperidol, considered as a specific blocker of dopamine receptors, produced a dose-dependent increase of total sleep and a decrease of paradoxical sleep. Chlorpromazine induced a different effect, that is a clear enhancement of paradoxical sleep. Taken together, these results indicate that an activation of dopamine systems in the brain is partly involved not only in behavioral activation, but also in cortical activation of waking and paradoxical sleep. The effect of chlorpromazine on paradoxical sleep cannot be attributed to the antidopaminergic properties of this drug.", "contents": "Brain dopamine receptors and sleep in the rat: effects of stimulation and blockade. A high dose of apomorphine, a stimulator of brain dopamine receptors, caused a reduction in total sleep, intermediate sleep and a delayed appearance of paradoxical sleep. With a lower dose, a small and not significant trend toward an increase of paradoxical sleep was observed. Spiroperidol, considered as a specific blocker of dopamine receptors, produced a dose-dependent increase of total sleep and a decrease of paradoxical sleep. Chlorpromazine induced a different effect, that is a clear enhancement of paradoxical sleep. Taken together, these results indicate that an activation of dopamine systems in the brain is partly involved not only in behavioral activation, but also in cortical activation of waking and paradoxical sleep. The effect of chlorpromazine on paradoxical sleep cannot be attributed to the antidopaminergic properties of this drug."} {"id": "PMID:182514", "title": "Quantitative studies of intracellular postsynaptic potentials in the lateral geniculate nucleus of the cat with respect to optic tract stimulus response latencies.", "content": "LGN cells were intracellularly recorded with glass micropipettes. Electrical stimuli of different amplitude and frequency were applied to the optic tract close to the optic chiasm. The cells were classified according to stimulus response latencies of action potentials as belonging to class I (1.0-16 msec) Or class II (1.7-3.0 MSEC). Class I EPSPs had shorter latencies (1.0-1.5 msec), durations (4-12 msec), rise times to peak (0.5-1.4 msec), and decay times (3.0-8.5 msec); the synaptic transmission time was on the average 0.41 msec. Class II EPSPs (1.6-2.6 msec latency) had longer durations (10-30 msec), rise times (1.6-3.7 msec), and decay times (9.0-25 msec); the synaptic transmission time was on the average 0.67 msec. With repetitive stimulation the EPSPs of latency class I revealed almost no stimulus frequency dependence between 1 and 120 HZ, while class 22 EPSPs decrease in amplitude between 30 and 70% with increasing frequency. Comparable temporal summation of excitation occurred in cells of both latency classes. Negative serial correlation coefficients of first order were found for consecutive EPSP amplitudes of all cells recorded for sufficient periods of time. The IPSPs were subdivided into two groups according to their optic tract response latency. Group 1 IPSPs had shorter latencies (2.0-2.6 msec), durations (15-50 msec), and times from the onset to maximal hyperpolarization (2.4-4.2 msec) than group 2 IPSPs (3.0-4.8 msec latency, 40-100 msec duration, 2.7-7.5 msec time from onset to extremum). The group 2 IPSPs decreased in amplitude by about 90% when the stimulus frequency was increased form 1 to 50 HZ, while the group 1 IPSPs displayed a comparable decrease in the frequency range between 50 and 120 HZ. Effective temporal summation was found in group 2 IPSPs in the frequency range below 70 HZ, and in group 1 IPSPs at stimulus frequencies between 70 and 120 HZ. The EPSP peak latencies and the latencies to the minimum of IPSPs proved to be invariant with respect to PSP amplitude and stimulus fre quency in individual cells. The latencies to the extrema of EPSPs and IPSPs as well as the amplitude values were symmetrically distributed.", "contents": "Quantitative studies of intracellular postsynaptic potentials in the lateral geniculate nucleus of the cat with respect to optic tract stimulus response latencies. LGN cells were intracellularly recorded with glass micropipettes. Electrical stimuli of different amplitude and frequency were applied to the optic tract close to the optic chiasm. The cells were classified according to stimulus response latencies of action potentials as belonging to class I (1.0-16 msec) Or class II (1.7-3.0 MSEC). Class I EPSPs had shorter latencies (1.0-1.5 msec), durations (4-12 msec), rise times to peak (0.5-1.4 msec), and decay times (3.0-8.5 msec); the synaptic transmission time was on the average 0.41 msec. Class II EPSPs (1.6-2.6 msec latency) had longer durations (10-30 msec), rise times (1.6-3.7 msec), and decay times (9.0-25 msec); the synaptic transmission time was on the average 0.67 msec. With repetitive stimulation the EPSPs of latency class I revealed almost no stimulus frequency dependence between 1 and 120 HZ, while class 22 EPSPs decrease in amplitude between 30 and 70% with increasing frequency. Comparable temporal summation of excitation occurred in cells of both latency classes. Negative serial correlation coefficients of first order were found for consecutive EPSP amplitudes of all cells recorded for sufficient periods of time. The IPSPs were subdivided into two groups according to their optic tract response latency. Group 1 IPSPs had shorter latencies (2.0-2.6 msec), durations (15-50 msec), and times from the onset to maximal hyperpolarization (2.4-4.2 msec) than group 2 IPSPs (3.0-4.8 msec latency, 40-100 msec duration, 2.7-7.5 msec time from onset to extremum). The group 2 IPSPs decreased in amplitude by about 90% when the stimulus frequency was increased form 1 to 50 HZ, while the group 1 IPSPs displayed a comparable decrease in the frequency range between 50 and 120 HZ. Effective temporal summation was found in group 2 IPSPs in the frequency range below 70 HZ, and in group 1 IPSPs at stimulus frequencies between 70 and 120 HZ. The EPSP peak latencies and the latencies to the minimum of IPSPs proved to be invariant with respect to PSP amplitude and stimulus fre quency in individual cells. The latencies to the extrema of EPSPs and IPSPs as well as the amplitude values were symmetrically distributed."} {"id": "PMID:182515", "title": "Influence of saccadic eye movements on geniculostriate excitability in normal monkeys.", "content": "Using permanently implanted electrodes in squirrel monkeys and macaques, transmission through the lateral geniculate nucleus (LGN) was assayed from the amplitude of potentials evoked in optic radiation by and electrical pulse applied to optic tract. Averaging of either individually or machine selected potentials, elicited at 0.3, 1.0, 20 or 50 HZ, in all cases showed a decrease in transmission ranging from 5-60% in the period after saccadic eye movements made ad libitum. The suppression was greater in a patterned visual environment than in diffuse illumination, which in turn was greater than that occurring following saccades in the dark. Demonstration of the effect in darkness always required data averaging and never exceeded 20%. The effect was consistently greater in the magnocellular than parvocellular component. Suppresion was often abruptly terminated and replaced by a facilitation of 5-15% about 100 msec after saccade detection. Comparable effects were observed for excitability of striate cortex tested by a stimulus pulse applied to optic radiation. In addition, sharply demarcated potentials inherently arising in LGN and striate cortex were found in association with saccades made even in total darkness. Neglecting a possible but dubious contribution from eye muscle proprioceptors, the experiments establish the existence of a centrally originating modulation of visual processing at both LGN and striate cortex in ralation to saccadic eye movement in primates. This modulation may partially underlie the phenomenon of \"saccadic suppression\" and hasten the acquistion of a meaningful visualsample immediately following an ocular saccade. It remains uncertain as to how it may relate to similar or greater effects accompanying changes in alertness, or to fluctuations of unknown origin occurring sometimes semirhythmically at 0.05-0.03 HZ (Fig 7).", "contents": "Influence of saccadic eye movements on geniculostriate excitability in normal monkeys. Using permanently implanted electrodes in squirrel monkeys and macaques, transmission through the lateral geniculate nucleus (LGN) was assayed from the amplitude of potentials evoked in optic radiation by and electrical pulse applied to optic tract. Averaging of either individually or machine selected potentials, elicited at 0.3, 1.0, 20 or 50 HZ, in all cases showed a decrease in transmission ranging from 5-60% in the period after saccadic eye movements made ad libitum. The suppression was greater in a patterned visual environment than in diffuse illumination, which in turn was greater than that occurring following saccades in the dark. Demonstration of the effect in darkness always required data averaging and never exceeded 20%. The effect was consistently greater in the magnocellular than parvocellular component. Suppresion was often abruptly terminated and replaced by a facilitation of 5-15% about 100 msec after saccade detection. Comparable effects were observed for excitability of striate cortex tested by a stimulus pulse applied to optic radiation. In addition, sharply demarcated potentials inherently arising in LGN and striate cortex were found in association with saccades made even in total darkness. Neglecting a possible but dubious contribution from eye muscle proprioceptors, the experiments establish the existence of a centrally originating modulation of visual processing at both LGN and striate cortex in ralation to saccadic eye movement in primates. This modulation may partially underlie the phenomenon of \"saccadic suppression\" and hasten the acquistion of a meaningful visualsample immediately following an ocular saccade. It remains uncertain as to how it may relate to similar or greater effects accompanying changes in alertness, or to fluctuations of unknown origin occurring sometimes semirhythmically at 0.05-0.03 HZ (Fig 7)."} {"id": "PMID:182516", "title": "Noradrenaline-refractoriness in cultured glioma cells.", "content": "Rat glioma cells in culture (subclone C6-SK71) respond to 0.1 mM noradrenaline by a 100 fold elevation of the intracellular cyclic AMP concentration, and by a subsequent change in morphology. The glioma cells extend multiple processes to resemble the morphology of normal astrocytes in brain tissue. Evidence is presented that the responses are mediated by way of a beta-adrenergic receptor. Both the biochemical and the morphological responses to noradrenaline are visible within minutes, but the cells revert to the untreated condition within 8 hours. Addition of fresh noradrenaline does not alter the sequence of events. A refractory period in which neither effect could be evoked by a subsequent exposure to noradrenaline was observed to last about 50 hours and was not correlated with a change in the rate of cell growth.", "contents": "Noradrenaline-refractoriness in cultured glioma cells. Rat glioma cells in culture (subclone C6-SK71) respond to 0.1 mM noradrenaline by a 100 fold elevation of the intracellular cyclic AMP concentration, and by a subsequent change in morphology. The glioma cells extend multiple processes to resemble the morphology of normal astrocytes in brain tissue. Evidence is presented that the responses are mediated by way of a beta-adrenergic receptor. Both the biochemical and the morphological responses to noradrenaline are visible within minutes, but the cells revert to the untreated condition within 8 hours. Addition of fresh noradrenaline does not alter the sequence of events. A refractory period in which neither effect could be evoked by a subsequent exposure to noradrenaline was observed to last about 50 hours and was not correlated with a change in the rate of cell growth."} {"id": "PMID:182517", "title": "Measurement of current spread from microelectrodes when stimulating within the nervous system.", "content": "Tungsten stimulating microelectrodes have been tested in monopolar, bipolar and concentric configurations for the extent to which unwanted current spread occurred. Current spread from monopolar electrodes in close conformity with the predictions of the inverse square law, both in vitro in vivo. The bipolar and concentric configurations, tested only in vitro, had current-spread characteristics which did not follow the inverse square law so closely. The bipolar configuration gave little reduction in spread, compared wpith a monopolar electrode, but the concentric configuration did reduce the extent of stimulus spread. The extent of spread depends greatly upon a number of experimental variables, including the dimensions of the microelectrode tip. For studies requiring precise localization with low stimulus currents, it is advisable to determine the inverse square law constant for each experimental situation. For more generalized stimulation purposes within the mammalian C.N.S., employing monopolar microelectrodes of moderate tip size, brief pulses of 10 muA can be expected to stimulate myelinated axons with about 0.15 mm of the tip, and 100 muA WILL Stimulate with a radius of about 0.5 mm.", "contents": "Measurement of current spread from microelectrodes when stimulating within the nervous system. Tungsten stimulating microelectrodes have been tested in monopolar, bipolar and concentric configurations for the extent to which unwanted current spread occurred. Current spread from monopolar electrodes in close conformity with the predictions of the inverse square law, both in vitro in vivo. The bipolar and concentric configurations, tested only in vitro, had current-spread characteristics which did not follow the inverse square law so closely. The bipolar configuration gave little reduction in spread, compared wpith a monopolar electrode, but the concentric configuration did reduce the extent of stimulus spread. The extent of spread depends greatly upon a number of experimental variables, including the dimensions of the microelectrode tip. For studies requiring precise localization with low stimulus currents, it is advisable to determine the inverse square law constant for each experimental situation. For more generalized stimulation purposes within the mammalian C.N.S., employing monopolar microelectrodes of moderate tip size, brief pulses of 10 muA can be expected to stimulate myelinated axons with about 0.15 mm of the tip, and 100 muA WILL Stimulate with a radius of about 0.5 mm."} {"id": "PMID:182520", "title": "Cyclic AMP during development and ageing of the insect Ceratitis capitata.", "content": "Cyclic AMP was determined during the development of the diptera Ceratitis capitata. The concentration of the nucleotide reaches a peak at apolysis with a sharp decline in the pharate adult stage. A gradual increase takes place through the longevity of adult stage reaching a maximum plateau at the end of life.", "contents": "Cyclic AMP during development and ageing of the insect Ceratitis capitata. Cyclic AMP was determined during the development of the diptera Ceratitis capitata. The concentration of the nucleotide reaches a peak at apolysis with a sharp decline in the pharate adult stage. A gradual increase takes place through the longevity of adult stage reaching a maximum plateau at the end of life."} {"id": "PMID:182521", "title": "Tele-encephalic versus cerebellar control upon ponto-geniculo-occipital waves during paradoxical sleep in the cat.", "content": "Studying the effects that removal of the cerebellum and the frontal lobes had upon the phasic activities (PGO waves) of paradoxical sleep in the cat, it is shown that in this phase of the sleep-wakefulness cycle the cerebellum exerts an inhibitory action upon the amplitude of the GPO, while the frontal lobes influences the pattern of their discharges.", "contents": "Tele-encephalic versus cerebellar control upon ponto-geniculo-occipital waves during paradoxical sleep in the cat. Studying the effects that removal of the cerebellum and the frontal lobes had upon the phasic activities (PGO waves) of paradoxical sleep in the cat, it is shown that in this phase of the sleep-wakefulness cycle the cerebellum exerts an inhibitory action upon the amplitude of the GPO, while the frontal lobes influences the pattern of their discharges."} {"id": "PMID:182522", "title": "The effect of combined chronic hypoxia and N-ethyl-N-nitrosourea on the carotid bodies of rats.", "content": "We measured the carotid body volume of rats treated with chronic hypoxia alone and chronic hypoxia together with a single neonatal injection of N-ethyl-N-nitrosourea (10 mg/kg). All the animals so treated showed enlargement of their carotid bodies, but no carotid body chemodectomas occurred.", "contents": "The effect of combined chronic hypoxia and N-ethyl-N-nitrosourea on the carotid bodies of rats. We measured the carotid body volume of rats treated with chronic hypoxia alone and chronic hypoxia together with a single neonatal injection of N-ethyl-N-nitrosourea (10 mg/kg). All the animals so treated showed enlargement of their carotid bodies, but no carotid body chemodectomas occurred."} {"id": "PMID:182523", "title": "Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues.", "content": "The PGE2-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino1]-[desamino1] [descarboxy14]- and [D-Lys4]-somatostatin similarly to somatostatin, while the [descarboxy14]-somatostatin exhibits reduced activity; [D-Lys9]-somatostatin is ineffective at a higher concentration.", "contents": "Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues. The PGE2-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino1]-[desamino1] [descarboxy14]- and [D-Lys4]-somatostatin similarly to somatostatin, while the [descarboxy14]-somatostatin exhibits reduced activity; [D-Lys9]-somatostatin is ineffective at a higher concentration."} {"id": "PMID:182524", "title": "Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma.", "content": "Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.", "contents": "Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma. Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein."} {"id": "PMID:182525", "title": "Failure to SV40-transformed lizard cells to induce tumors in autogeneic or allogeneic hosts.", "content": "Lizard cells from the tails of geckos were readily morphologically and antigenically transformed in vitro by SV40 virus. Neither autografts of these cells nor allografts of SV40 transformed gecko embryo cells produced tumors in animals under observation for 1 to 3 years.", "contents": "Failure to SV40-transformed lizard cells to induce tumors in autogeneic or allogeneic hosts. Lizard cells from the tails of geckos were readily morphologically and antigenically transformed in vitro by SV40 virus. Neither autografts of these cells nor allografts of SV40 transformed gecko embryo cells produced tumors in animals under observation for 1 to 3 years."} {"id": "PMID:182526", "title": "On the mineralocorticoid and hypertensogenic properties of 16beta-hydroxy-dehydroepiandrosterone.", "content": "Dosages of either 1 or 2 mg daily of 16beta-hydroxy-dehydroepiandrosterone, given to mononephrectomized, salt-loaded female rats, had no detectable effect upon saline consumption, blood pressure, kallikrein excretion or heart and kidney weight. Its alleged mineralocorticoid properties, as judged by these criteria, were not demonstrable.", "contents": "On the mineralocorticoid and hypertensogenic properties of 16beta-hydroxy-dehydroepiandrosterone. Dosages of either 1 or 2 mg daily of 16beta-hydroxy-dehydroepiandrosterone, given to mononephrectomized, salt-loaded female rats, had no detectable effect upon saline consumption, blood pressure, kallikrein excretion or heart and kidney weight. Its alleged mineralocorticoid properties, as judged by these criteria, were not demonstrable."} {"id": "PMID:182527", "title": "Effect of progesterone on the in vivo binding of estrogens by uterine cells.", "content": "Progesterone selectively inhibits estradiol uptake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.", "contents": "Effect of progesterone on the in vivo binding of estrogens by uterine cells. Progesterone selectively inhibits estradiol uptake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only."} {"id": "PMID:182528", "title": "Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron.", "content": "Relations among circadian rhythms in serum iron, glucagon and insulin and urinary cyclic AMP excretion differ drastically when diurnally active, nocturnally resting human adults consume all daily food for one week as breakfast only and for another week as dinner only - a finding of interest to diverse fields, e.g., for optimizing certain kinds of therapy or for a better utilization of calories.", "contents": "Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron. Relations among circadian rhythms in serum iron, glucagon and insulin and urinary cyclic AMP excretion differ drastically when diurnally active, nocturnally resting human adults consume all daily food for one week as breakfast only and for another week as dinner only - a finding of interest to diverse fields, e.g., for optimizing certain kinds of therapy or for a better utilization of calories."} {"id": "PMID:182529", "title": "Rapid purification of lactate dehydrogenase X from mouse testes by two steps of affinity chromatography on oxamate-sepharose.", "content": "At concentrations of 200 muM NADH and 0.5 M NaCl LDH-X is separated from the other LDH isozymes of mouse testes on oxamate-sepharose. In a second step LDH-X is bound to the same matrix at lower NADH and NaCl concentrations and the pure enzyme can subsequently be eluted.", "contents": "Rapid purification of lactate dehydrogenase X from mouse testes by two steps of affinity chromatography on oxamate-sepharose. At concentrations of 200 muM NADH and 0.5 M NaCl LDH-X is separated from the other LDH isozymes of mouse testes on oxamate-sepharose. In a second step LDH-X is bound to the same matrix at lower NADH and NaCl concentrations and the pure enzyme can subsequently be eluted."} {"id": "PMID:182555", "title": "Intermediary metabolism of adipose tissue.", "content": "Metabolism of ruminant adipocytes involves the synthesis and mobilization of lipids. Rates of lipid synthesis from the uptake of preformed fatty acids (via lipoprotein lipase) and de novo synthesis of fatty acids are related to the energy balance. Acetate is the major carbon source for fatty acid synthesis with NADPH originating from the pentose cycle and the isocitrate cycle. Ruminant adipose tissue lacks the ability to utilize for lipogenesis those substrates that generate mitochondrial acetyl CoA because of an absence of ATP citrate-lyase and NADP-malate dehydrogenase. Lipid mobilization in ruminant adipocytes is apparently regulated via cAMP levels and a summary of the compounds investigated for lipolytic responses is presented. The control of lipid synthesis and mobilization is interrelated in ruminant adipose tissue. The coordinated manner in which these two functions are regulated is examined with regard to adipocyte responses to insulin and epinephrine. In both lipid synthesis and lipid mobilization, ruminant adipocytes are uniquely different from nonruminant adipose tissue. The physiological significance and possible basis for these species differences in adipose metabolism are discussed.", "contents": "Intermediary metabolism of adipose tissue. Metabolism of ruminant adipocytes involves the synthesis and mobilization of lipids. Rates of lipid synthesis from the uptake of preformed fatty acids (via lipoprotein lipase) and de novo synthesis of fatty acids are related to the energy balance. Acetate is the major carbon source for fatty acid synthesis with NADPH originating from the pentose cycle and the isocitrate cycle. Ruminant adipose tissue lacks the ability to utilize for lipogenesis those substrates that generate mitochondrial acetyl CoA because of an absence of ATP citrate-lyase and NADP-malate dehydrogenase. Lipid mobilization in ruminant adipocytes is apparently regulated via cAMP levels and a summary of the compounds investigated for lipolytic responses is presented. The control of lipid synthesis and mobilization is interrelated in ruminant adipose tissue. The coordinated manner in which these two functions are regulated is examined with regard to adipocyte responses to insulin and epinephrine. In both lipid synthesis and lipid mobilization, ruminant adipocytes are uniquely different from nonruminant adipose tissue. The physiological significance and possible basis for these species differences in adipose metabolism are discussed."} {"id": "PMID:182556", "title": "The specificity of gonadotropin binding by the human corpus luteum.", "content": "The specificity of gonadotropin binding was studied in fresh and frozen human corpora lutea. Ovine, bovine, and porcine luteinizing hormone (LH) competed with 125I-labeled human LH (125I-hLH) and 125I-labeled human chorionic gonadotropin (125I-hCG) for binding to tissue receptors in homogenates of human corpora lutea frozen for 3 to 12 months. In contrast, oLH, bLH, and pLH competed minimally for 125I-hLH and 125I-hCG binding sites in homogenates of fresh human corpora lutea. Ovine follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) did not compete in homogenates of fresh or frozen tissue. Competition of oLH and hCG for 125I-hCG binding sites at several dose levels in a homogenate of a fresh corpus luteum was studied. One hundred micrograms of oLH and ten nanograms of hCG gave an equivalent competition--a 10,000-fold difference in competitive potency. Only hCG competed with 125I-hCG for binding when the competition of oLH, bLH, pLH, oFSH, oTSH, hCG and hCG subunits, and hCG were compared at the 10-mug level in a homogenate of fresh human corpus luteum. The binding of 125I-labeled homologous human hormones by the corpus luteum was examined in a limited fashion. 125I-Prolactin did not bind to preparations of fresh stroma from a patient with polycystic ovaries nor did it bind to three separate preparations of fresh corpora luteum which did bind 125I-hCG. 125I-hTSH did not show significant binding to a fresh human corpus luteum preparation which did bind 125I-hCG. These studies indicate that the gonadotropin receptor of the fresh human corpus luteum possesses a unique species specificity and illustrate the importance of working with human corpora lutea in their most native state.", "contents": "The specificity of gonadotropin binding by the human corpus luteum. The specificity of gonadotropin binding was studied in fresh and frozen human corpora lutea. Ovine, bovine, and porcine luteinizing hormone (LH) competed with 125I-labeled human LH (125I-hLH) and 125I-labeled human chorionic gonadotropin (125I-hCG) for binding to tissue receptors in homogenates of human corpora lutea frozen for 3 to 12 months. In contrast, oLH, bLH, and pLH competed minimally for 125I-hLH and 125I-hCG binding sites in homogenates of fresh human corpora lutea. Ovine follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) did not compete in homogenates of fresh or frozen tissue. Competition of oLH and hCG for 125I-hCG binding sites at several dose levels in a homogenate of a fresh corpus luteum was studied. One hundred micrograms of oLH and ten nanograms of hCG gave an equivalent competition--a 10,000-fold difference in competitive potency. Only hCG competed with 125I-hCG for binding when the competition of oLH, bLH, pLH, oFSH, oTSH, hCG and hCG subunits, and hCG were compared at the 10-mug level in a homogenate of fresh human corpus luteum. The binding of 125I-labeled homologous human hormones by the corpus luteum was examined in a limited fashion. 125I-Prolactin did not bind to preparations of fresh stroma from a patient with polycystic ovaries nor did it bind to three separate preparations of fresh corpora luteum which did bind 125I-hCG. 125I-hTSH did not show significant binding to a fresh human corpus luteum preparation which did bind 125I-hCG. These studies indicate that the gonadotropin receptor of the fresh human corpus luteum possesses a unique species specificity and illustrate the importance of working with human corpora lutea in their most native state."} {"id": "PMID:182564", "title": "[The effect of metallic ions on steroid hormone receptors in the rabbit uterus (author's transl)].", "content": "The copper-IUD has been proved to be more effective for contraception than the popular IUD. To understand this mechanism of action, the effects of metallic ions on estrogen and progesterone receptors were examined in the cytosol of estrogen primed with female rabbits. The 274,200 X G supernatant of the uterine homogenate was used as the cytosol. The cytosol and 3H-progesterone (3.12 X 10(-9)M) or 3H-estradiol-17 beta (3.46 X 10(-9)M), with or without various metallic ions of different concentrations had been incubated for 2 hours. Bindings of steroids were estimated by the dextran coated charcoal assay (0.001% dextran and 0.1% Norite A) and were evaluated by 5 approximately 20% sucrose linear gradient centrifugation 1) Effect of various metallic ions on steroid hormone-receptor binding (determined by dextran coated charcoal assay. Fig. 1) : Thesteroid hormone-receptor interactions were markedly inhibited by Cu++, Fe++, and Zn++ ions and moderately by Mn++, but K+ and Ca++ increased of slightly affected the binding at concentrations between 10(-2)M and 10(-4)M. There were some differences between estrogen and progesterone receptors in their sensitivities to various metallic ions. 2) The effect of copper ion on the binding of steroid to the receptor : The dextran coated charcoal assay (Fig. 2) demonstrated that the inhibitory effect of Cu++ appeared at 10(-6)M and the steroidhormone-receptor bound decreased down to 10% at 10(-2)M Cu++. The estrogen receptor was less affected by copper than the progesterone receptor. It was demonstrated by 5 approximately 20% sucrose linear gradient centrifugation (Fig 3) that estrogen and progesterone receptors, which both sedimented at 8 S, were changed to more sedimenting forms in the presence of 10(-4)M Cu++, and were dissociated to 6.5 S form with moderate loss of steriod hormone binding affinity in 10(-2)M Cu++. The kinetic study (Fig 4), determined by dextran coated charcoal, showed that Cu++ was a competitive inhibitor against steroid hormone receptor bindings with Ki in equilibrium 2.7 X 10(-5)M to estrogen receptor (Kd in equilibrium 1.4 X 10(-9)M), and with Ki in equilibrium 5.1 X 10(-6M to progesterone receptor (Kd in equilibrium 8.1 X 10(-10)M). These results indicate the inhibiting factor of copper is the direct interference at the steriod binding site of the receptor, resulting in the increase in the effectiveness of the IUD. While progesterone receptor is more affected by copper ion than estrogen receptor, it is suggested that estrogen receptor survives longer than progesterone receptor and thus the biolgoical effect of copper seems to be somewhat estrogenic.", "contents": "[The effect of metallic ions on steroid hormone receptors in the rabbit uterus (author's transl)]. The copper-IUD has been proved to be more effective for contraception than the popular IUD. To understand this mechanism of action, the effects of metallic ions on estrogen and progesterone receptors were examined in the cytosol of estrogen primed with female rabbits. The 274,200 X G supernatant of the uterine homogenate was used as the cytosol. The cytosol and 3H-progesterone (3.12 X 10(-9)M) or 3H-estradiol-17 beta (3.46 X 10(-9)M), with or without various metallic ions of different concentrations had been incubated for 2 hours. Bindings of steroids were estimated by the dextran coated charcoal assay (0.001% dextran and 0.1% Norite A) and were evaluated by 5 approximately 20% sucrose linear gradient centrifugation 1) Effect of various metallic ions on steroid hormone-receptor binding (determined by dextran coated charcoal assay. Fig. 1) : Thesteroid hormone-receptor interactions were markedly inhibited by Cu++, Fe++, and Zn++ ions and moderately by Mn++, but K+ and Ca++ increased of slightly affected the binding at concentrations between 10(-2)M and 10(-4)M. There were some differences between estrogen and progesterone receptors in their sensitivities to various metallic ions. 2) The effect of copper ion on the binding of steroid to the receptor : The dextran coated charcoal assay (Fig. 2) demonstrated that the inhibitory effect of Cu++ appeared at 10(-6)M and the steroidhormone-receptor bound decreased down to 10% at 10(-2)M Cu++. The estrogen receptor was less affected by copper than the progesterone receptor. It was demonstrated by 5 approximately 20% sucrose linear gradient centrifugation (Fig 3) that estrogen and progesterone receptors, which both sedimented at 8 S, were changed to more sedimenting forms in the presence of 10(-4)M Cu++, and were dissociated to 6.5 S form with moderate loss of steriod hormone binding affinity in 10(-2)M Cu++. The kinetic study (Fig 4), determined by dextran coated charcoal, showed that Cu++ was a competitive inhibitor against steroid hormone receptor bindings with Ki in equilibrium 2.7 X 10(-5)M to estrogen receptor (Kd in equilibrium 1.4 X 10(-9)M), and with Ki in equilibrium 5.1 X 10(-6M to progesterone receptor (Kd in equilibrium 8.1 X 10(-10)M). These results indicate the inhibiting factor of copper is the direct interference at the steriod binding site of the receptor, resulting in the increase in the effectiveness of the IUD. While progesterone receptor is more affected by copper ion than estrogen receptor, it is suggested that estrogen receptor survives longer than progesterone receptor and thus the biolgoical effect of copper seems to be somewhat estrogenic."} {"id": "PMID:182565", "title": "[Effects of low salt plus upright posture, angiotensin II, ACTH, and potassium upon plasma renin activity, aldosterone, and cortisol (author's transl)].", "content": "In order to study the control system of plasma aldosterone in human, we examined the effects of low salt plus upright posture, angiotensin II, ACTH and potassium upon plasma renin activity, aldosterone and cortisol in five subjects who were supposed to be normal. All of the procedures, low salt diet with below 3 g of salt and 2 hr-upright posture, 0.25 mg of Cortrosyn, angiotensin infusion to increase 20mmHG of diastolic pressure for an hour, and 30 mEq of potassium infusion stimulated plasma aldosterone significantly. Furthermore, in each subject the degrees of response to each of these stimulations were almost same. In an old woman aged 68, responses to all of stimulations were significantly lower than those in other subjects. Plasma cortisol was significantly stimulated by ACTH, but slightly reduced by potassium infusion. From these results, it is certain that plasma aldosteron levels are easily affected by a small amount of changes in angiotensin, ACTH, potassium and sodium. However, responses of aldosterone to these changes seem to be decreased in old subjects.", "contents": "[Effects of low salt plus upright posture, angiotensin II, ACTH, and potassium upon plasma renin activity, aldosterone, and cortisol (author's transl)]. In order to study the control system of plasma aldosterone in human, we examined the effects of low salt plus upright posture, angiotensin II, ACTH and potassium upon plasma renin activity, aldosterone and cortisol in five subjects who were supposed to be normal. All of the procedures, low salt diet with below 3 g of salt and 2 hr-upright posture, 0.25 mg of Cortrosyn, angiotensin infusion to increase 20mmHG of diastolic pressure for an hour, and 30 mEq of potassium infusion stimulated plasma aldosterone significantly. Furthermore, in each subject the degrees of response to each of these stimulations were almost same. In an old woman aged 68, responses to all of stimulations were significantly lower than those in other subjects. Plasma cortisol was significantly stimulated by ACTH, but slightly reduced by potassium infusion. From these results, it is certain that plasma aldosteron levels are easily affected by a small amount of changes in angiotensin, ACTH, potassium and sodium. However, responses of aldosterone to these changes seem to be decreased in old subjects."} {"id": "PMID:182566", "title": "[Studies on the responsiveness of human adrenocortical tumors to ACTH the clinical and experimental observations (author's transl)].", "content": "Six cases of Cushing's syndrome with adrenocortical tumors which showed a variety of responsiveness to ACTH were investigated in relation to their clinical pictures and laboratory findings. Abnormal responses to ACTH in tumors was analyzed by in vitro experiments with surgically obtained tumor tissues, and the ACTH responsive mechanism of the tumors was discussed. An 8 hour intravenous ACTH infusion test showed that three of these patients were ACTH responsive, and the other three unresponsive. Histological observation of the tumors revealed that ACTH responsive tumors were adenomas and that ACTH unresponsive tumors were \"black adenomas\" in two and a carcinoma in one. To investigate possible factors which might account for these differences in ACTH responsiveness, tumor specimens of each one of the responsive and unresponsive adenomas, and a carcinoma were subjected to in vitro studies. When incubated with ACTH or cyclic AMP, tissue sections of a responsive adenoma enhanced cortisol secretion, while that of a black adenoma failed to show any change. Steroidogenesis by carcinoma sections were significantly suppressed in the presence of ACTH or cyclic AMP. Cycloheximide abolished a stimulatory effect of ACTH and cyclic AMP on steroidogenesis in a responsive adenoma without affecting its basal secretion of cortisol. Steroidogenesis by unresponsive tumors (an adenoma and a carcinoma) were decreased by cycloheximide. Since the conversion of cholesterol to pregnenolone, the rate limiting step in steroidogenesis, takes place in adrenal mitochondria, the effect of cyclic AMP on pregnenolone formation from 14C-cholesterol by mitochondrial fractions of these tumors was examined. Cyclic AMP stimulated pregnenolone formation by mitochondrial fraction of an ACTH responsive adenoma, while with that of an unresponsive adenoma pregnenolone formation was not affected. Pregnenolone formation by cancer mitochondria was significantly suppressed by cyclic AMP. These results suggest that the unresponsiveness to ACTH of these tumors might be explained by the ineffectiveness of cyclic AMP to stimulate pregnenolone formation by tumor mitochondria, and that the steroidogenic pathway in unresponsive tumors are in an enhanced state even without cyclic AMP. It should be mentioned that all unresponsive adenomas gave a characteristic appearance of a \"black adenoma\". Histologically, tumors were composed of compact cells with abundant lipofuscin granules. The possible relationship between the ACTH responsiveness of adrenocortical tumors and some clinical pictures caused by them was also noticed. ACTH unresponsive adenomas resulted in shorter duration, severer conditions of the disease and higher 17-ketosteroid excretion than responsive adenomas. The growth of unresponsive tumors seemed faster than that of responsive ones.", "contents": "[Studies on the responsiveness of human adrenocortical tumors to ACTH the clinical and experimental observations (author's transl)]. Six cases of Cushing's syndrome with adrenocortical tumors which showed a variety of responsiveness to ACTH were investigated in relation to their clinical pictures and laboratory findings. Abnormal responses to ACTH in tumors was analyzed by in vitro experiments with surgically obtained tumor tissues, and the ACTH responsive mechanism of the tumors was discussed. An 8 hour intravenous ACTH infusion test showed that three of these patients were ACTH responsive, and the other three unresponsive. Histological observation of the tumors revealed that ACTH responsive tumors were adenomas and that ACTH unresponsive tumors were \"black adenomas\" in two and a carcinoma in one. To investigate possible factors which might account for these differences in ACTH responsiveness, tumor specimens of each one of the responsive and unresponsive adenomas, and a carcinoma were subjected to in vitro studies. When incubated with ACTH or cyclic AMP, tissue sections of a responsive adenoma enhanced cortisol secretion, while that of a black adenoma failed to show any change. Steroidogenesis by carcinoma sections were significantly suppressed in the presence of ACTH or cyclic AMP. Cycloheximide abolished a stimulatory effect of ACTH and cyclic AMP on steroidogenesis in a responsive adenoma without affecting its basal secretion of cortisol. Steroidogenesis by unresponsive tumors (an adenoma and a carcinoma) were decreased by cycloheximide. Since the conversion of cholesterol to pregnenolone, the rate limiting step in steroidogenesis, takes place in adrenal mitochondria, the effect of cyclic AMP on pregnenolone formation from 14C-cholesterol by mitochondrial fractions of these tumors was examined. Cyclic AMP stimulated pregnenolone formation by mitochondrial fraction of an ACTH responsive adenoma, while with that of an unresponsive adenoma pregnenolone formation was not affected. Pregnenolone formation by cancer mitochondria was significantly suppressed by cyclic AMP. These results suggest that the unresponsiveness to ACTH of these tumors might be explained by the ineffectiveness of cyclic AMP to stimulate pregnenolone formation by tumor mitochondria, and that the steroidogenic pathway in unresponsive tumors are in an enhanced state even without cyclic AMP. It should be mentioned that all unresponsive adenomas gave a characteristic appearance of a \"black adenoma\". Histologically, tumors were composed of compact cells with abundant lipofuscin granules. The possible relationship between the ACTH responsiveness of adrenocortical tumors and some clinical pictures caused by them was also noticed. ACTH unresponsive adenomas resulted in shorter duration, severer conditions of the disease and higher 17-ketosteroid excretion than responsive adenomas. The growth of unresponsive tumors seemed faster than that of responsive ones."} {"id": "PMID:182567", "title": "[Effect of cyclic AMP and Ca++ on steroidogenesis by rat adrenal mitochondrial fraction. Studies on the mechanism of ACTH action (I) (author's transl)].", "content": "Despite the accumulation of a number of studies, the mechanism of action of ACTH remains to be clarified. Although it is now clear that cyclic AMP acts as a intracellular mediator of ACTH action, the mechanism of its action on the stimulation of steroidogenesis is not known. The present studies were carried out to test the hypothesis that cyclic AMP might act directly on adrenal mitochondrial fraction to stimulate the metabolism of cholesterol to pregnenolone and progesterone, and to determine whether Ca++ might modulate the action of cyclic AMP. Adrenal mitochondria were obtained from male Sprague-Dawley rats pretreated with dexamethasone. Steroidogenesis by the mitochondrial fraction from cholesterol-4-14C (0.2-0.25 muCi, 3.6-4.5 mmumole/sample) were measured in a system containing 20 mM tris-HCl buffer (pH 7.4), 11.5 mM NaCl, 15.4 mM KCl, 70 mM sucrose, 10 mM sodium succinate and mitochondrial fraction (0.16-0.22 mg protein/sample). Incubations were performed at 37 degrees C, with shaking, in the presence or absence of cyclic AMP, cyclic GMP and cycloheximide. After incubation, the medium was extracted with chloroform, and the extracts were analyzed by thin-layer chromatography. And the radioactivity of the separated steroids was measured. The products from cholesterol-4-14C were mainly pregnenolone and progesterone, and the other products were almost negligible. Cyclic AMP effected the formation of pregnenolone and progesterone by mitochondria. Cyclic AMP exerted its effect even at low concentrations (5 X 10(-6) approximately 5 X 10(-5)M), which was presumably near the intracellular level. On the other hand, cyclic GMP (5 X 10(-5) M) failed to enhance steroidogenesis. The effect of Ca++ on the action of various concentrations (5 X 10(-6) approximately 3 X 10(-3) M) of cyclic AMP was also clearly demonstrated. Addition of Ca++ (1 mM) to the incubation medium intensified the stimulatory effect of cyclic AMP in each concentration. And in the presence of Ca++, the most effective level of cyclic AMP was shifted from 5 X 10(-4) approximately 3 X 10(-3)M to the lower concentration (5 X 10(-5)M). In addition, cyclic AMP action was modified by the changes in the concentration of Ca++ in the medium. At concentration of 10(-6) M of Ca++, steroid formation of mitochondria was maximally activated by cyclic AMP. These observations suggest that cyclic AMP enhances steroidogenesis by acting directly on adrenal mitochondria to stimulate pregnenolone and progesterone formation from cholesterol, and that Ca++ plays a significant role in its action.", "contents": "[Effect of cyclic AMP and Ca++ on steroidogenesis by rat adrenal mitochondrial fraction. Studies on the mechanism of ACTH action (I) (author's transl)]. Despite the accumulation of a number of studies, the mechanism of action of ACTH remains to be clarified. Although it is now clear that cyclic AMP acts as a intracellular mediator of ACTH action, the mechanism of its action on the stimulation of steroidogenesis is not known. The present studies were carried out to test the hypothesis that cyclic AMP might act directly on adrenal mitochondrial fraction to stimulate the metabolism of cholesterol to pregnenolone and progesterone, and to determine whether Ca++ might modulate the action of cyclic AMP. Adrenal mitochondria were obtained from male Sprague-Dawley rats pretreated with dexamethasone. Steroidogenesis by the mitochondrial fraction from cholesterol-4-14C (0.2-0.25 muCi, 3.6-4.5 mmumole/sample) were measured in a system containing 20 mM tris-HCl buffer (pH 7.4), 11.5 mM NaCl, 15.4 mM KCl, 70 mM sucrose, 10 mM sodium succinate and mitochondrial fraction (0.16-0.22 mg protein/sample). Incubations were performed at 37 degrees C, with shaking, in the presence or absence of cyclic AMP, cyclic GMP and cycloheximide. After incubation, the medium was extracted with chloroform, and the extracts were analyzed by thin-layer chromatography. And the radioactivity of the separated steroids was measured. The products from cholesterol-4-14C were mainly pregnenolone and progesterone, and the other products were almost negligible. Cyclic AMP effected the formation of pregnenolone and progesterone by mitochondria. Cyclic AMP exerted its effect even at low concentrations (5 X 10(-6) approximately 5 X 10(-5)M), which was presumably near the intracellular level. On the other hand, cyclic GMP (5 X 10(-5) M) failed to enhance steroidogenesis. The effect of Ca++ on the action of various concentrations (5 X 10(-6) approximately 3 X 10(-3) M) of cyclic AMP was also clearly demonstrated. Addition of Ca++ (1 mM) to the incubation medium intensified the stimulatory effect of cyclic AMP in each concentration. And in the presence of Ca++, the most effective level of cyclic AMP was shifted from 5 X 10(-4) approximately 3 X 10(-3)M to the lower concentration (5 X 10(-5)M). In addition, cyclic AMP action was modified by the changes in the concentration of Ca++ in the medium. At concentration of 10(-6) M of Ca++, steroid formation of mitochondria was maximally activated by cyclic AMP. These observations suggest that cyclic AMP enhances steroidogenesis by acting directly on adrenal mitochondria to stimulate pregnenolone and progesterone formation from cholesterol, and that Ca++ plays a significant role in its action."} {"id": "PMID:182570", "title": "Characterization of two forms of cyclic 3', 5'-adenosine monophosphate-dependent protein kinase in rat testicular interstitial cells.", "content": "The adenosine 3', 5'-cyclic monophosphate (cyclic AMP)-dependent protein phosphokinase of rat interstitial cells was characterized by ion-exchange chromatography and sucrose density gradient centrifugation. The 0.2 M NaCl fraction from DEAE-Sephadex showed a small 2.9-S peak of basal enzyme activity, and a large 6.5-S peak of cyclic AMP-dependent protein kinase activity; fractions eluted from DEAE-Sephadex with 0.3-0.5 M NaCl contained a major 3.8-S peak of cyclic AMP-dependent enzyme activity. Activation of protein kinase in cell extracts by cyclic AMP, and in intact interstitial cells by trophic hormone, caused a major shift of enzyme activity to the 2.9-S cyclic AMP-dependent form which was eluted from DEAE-Sephadex by 0.2 M NaCl. These results are consistent with the presence of two distinct protein kinase holoenzymes, with a common 2.9-S catalytic subunit. During hormonal activation of protein kinase in dispersed interstitial cells by 10-10 M human chorionic gonadotropin (hCG), conversion to the 2.9-S catalytic subunit was observed between 2 and 30 min of incubation. Protein kinase activity was correlated with cyclic AMP production, and full enzyme activation occurred at the time of maximum intracellular cyclic AMP concentration. The presence of two forms of cyclic AMP-dependent protein kinase in the Leydig cell provides a potential mechanism whereby progressive occupancy of gonadotropin receptors could evoke a series of discrete target cell responses.", "contents": "Characterization of two forms of cyclic 3', 5'-adenosine monophosphate-dependent protein kinase in rat testicular interstitial cells. The adenosine 3', 5'-cyclic monophosphate (cyclic AMP)-dependent protein phosphokinase of rat interstitial cells was characterized by ion-exchange chromatography and sucrose density gradient centrifugation. The 0.2 M NaCl fraction from DEAE-Sephadex showed a small 2.9-S peak of basal enzyme activity, and a large 6.5-S peak of cyclic AMP-dependent protein kinase activity; fractions eluted from DEAE-Sephadex with 0.3-0.5 M NaCl contained a major 3.8-S peak of cyclic AMP-dependent enzyme activity. Activation of protein kinase in cell extracts by cyclic AMP, and in intact interstitial cells by trophic hormone, caused a major shift of enzyme activity to the 2.9-S cyclic AMP-dependent form which was eluted from DEAE-Sephadex by 0.2 M NaCl. These results are consistent with the presence of two distinct protein kinase holoenzymes, with a common 2.9-S catalytic subunit. During hormonal activation of protein kinase in dispersed interstitial cells by 10-10 M human chorionic gonadotropin (hCG), conversion to the 2.9-S catalytic subunit was observed between 2 and 30 min of incubation. Protein kinase activity was correlated with cyclic AMP production, and full enzyme activation occurred at the time of maximum intracellular cyclic AMP concentration. The presence of two forms of cyclic AMP-dependent protein kinase in the Leydig cell provides a potential mechanism whereby progressive occupancy of gonadotropin receptors could evoke a series of discrete target cell responses."} {"id": "PMID:182571", "title": "Biphasic effect of testosterone propionate on Sertoli cell secretory function.", "content": "When various doses of testosterone propionate (10 to 10,000 mug/day) were given to 21-day-old rats for 10 days a biphasic effect was seen both on testis weight and production of androgen-binding protein (ABP). At low doses (10 to 100 mug testosterone propionate/day) there was a reduction in testis weight as well as ABP content in the epididymis. At higher doses of testosterone propionate, there was a stimulation of both testicular weight and ABP production in spite of suppressed serum FSH and LH levels. These effects of testosterone propionate on Sertoli cell secretory function strongly suggest that the Sertoli cell is a target cell for androgen.", "contents": "Biphasic effect of testosterone propionate on Sertoli cell secretory function. When various doses of testosterone propionate (10 to 10,000 mug/day) were given to 21-day-old rats for 10 days a biphasic effect was seen both on testis weight and production of androgen-binding protein (ABP). At low doses (10 to 100 mug testosterone propionate/day) there was a reduction in testis weight as well as ABP content in the epididymis. At higher doses of testosterone propionate, there was a stimulation of both testicular weight and ABP production in spite of suppressed serum FSH and LH levels. These effects of testosterone propionate on Sertoli cell secretory function strongly suggest that the Sertoli cell is a target cell for androgen."} {"id": "PMID:182572", "title": "The effects of cholera toxin on the adrenal weight in hypophysectomized rats.", "content": "The effects of cholera on adrenal weight in hypophysectomized rats were investigated, in an attempt to demonstrate an ACTH-like, adrenal trophic effect of the toxin. The results suggested that the toxin probably exerts is ACTH-like action on the adrenal via adenylate cyclase. Cholera toxin was also shown to have a thermolytic action, similar to that of ACTH, probably due to stimulation of adrenal glucocorticoid secretion.", "contents": "The effects of cholera toxin on the adrenal weight in hypophysectomized rats. The effects of cholera on adrenal weight in hypophysectomized rats were investigated, in an attempt to demonstrate an ACTH-like, adrenal trophic effect of the toxin. The results suggested that the toxin probably exerts is ACTH-like action on the adrenal via adenylate cyclase. Cholera toxin was also shown to have a thermolytic action, similar to that of ACTH, probably due to stimulation of adrenal glucocorticoid secretion."} {"id": "PMID:182573", "title": "Partial purification of the activated hepatic glucocorticoid - receptor complex.", "content": "A rapid procedure for the purification of the hepatic glucocorticoid receptor has been developed which exploits the observation that \"activation\" of this complex enables it to bind to anionic substances such as DNA and phosphocellulose. The procedure consists of two phosphocellulose columns operated in sequence. The first column removes from unfractionated cytosol all basic proteins which adhere to the immobilized phosphate residues; the steroid - receptor complex elutes in the flow-through of this first column. This complex is then thermally activated and applied to a second phosphocellulose column where it is retained, washed, and eluted by a salt gradient. This simple procedure is capable of purifying the steroid - receptor complex over 1000-fold.", "contents": "Partial purification of the activated hepatic glucocorticoid - receptor complex. A rapid procedure for the purification of the hepatic glucocorticoid receptor has been developed which exploits the observation that \"activation\" of this complex enables it to bind to anionic substances such as DNA and phosphocellulose. The procedure consists of two phosphocellulose columns operated in sequence. The first column removes from unfractionated cytosol all basic proteins which adhere to the immobilized phosphate residues; the steroid - receptor complex elutes in the flow-through of this first column. This complex is then thermally activated and applied to a second phosphocellulose column where it is retained, washed, and eluted by a salt gradient. This simple procedure is capable of purifying the steroid - receptor complex over 1000-fold."} {"id": "PMID:182574", "title": "Apparent multiple forms of cyclic AMP phosphodiesterase from rat erythrocytes.", "content": "Bio-Gel A-5m chromatography has been used to separate apparent multiple forms of cyclic nucleotide phosphodiesterase from rat erythrocytes. Cyclic AMP phosphodiesterase was resolved by gel filtration into three peaks of activity with apparent molecular weights of about 300,000, 225,000 and 100,000, while cyclic GMP phosphodiesterase activity in gel column fractions was too low to permit meaningful estimates of its molecular weight. All three of the separated peaks of cyclic AMP phosphodiesterase activity displayed anomalous kinetic behaviour suggestive of negative cooperativity. The possibility that multiple phosphodiesterase activities could arise from in vitro alterations of a single enzyme was investigated. Similar changes in gel filtration profiles resulted when erythrocyte extracts were treated with trypsin or ammonium sulfate or were incubated at 37 degrees C. After these treatments, a large proportion of the enzyme activity occurred in low (ca. 100,000) molecular weight regions. The low molecular weight phosphodiesterase activities from untreated, incubated, and trypsin-treated extracts possessed similar properties. All were inhibited by methylxanthines, had pH optima of approximately 8.0, and similar kinetic properties and requirements for divalent cations. These observations raise the possibility that preparative procedures or limited proteolysis occurring during preparation and handling of extracts can contribute to the apparent multiplicity of enzyme forms seen after gel filtration of phosphodiesterase from rat erythrocytes and perhaps other cell types.", "contents": "Apparent multiple forms of cyclic AMP phosphodiesterase from rat erythrocytes. Bio-Gel A-5m chromatography has been used to separate apparent multiple forms of cyclic nucleotide phosphodiesterase from rat erythrocytes. Cyclic AMP phosphodiesterase was resolved by gel filtration into three peaks of activity with apparent molecular weights of about 300,000, 225,000 and 100,000, while cyclic GMP phosphodiesterase activity in gel column fractions was too low to permit meaningful estimates of its molecular weight. All three of the separated peaks of cyclic AMP phosphodiesterase activity displayed anomalous kinetic behaviour suggestive of negative cooperativity. The possibility that multiple phosphodiesterase activities could arise from in vitro alterations of a single enzyme was investigated. Similar changes in gel filtration profiles resulted when erythrocyte extracts were treated with trypsin or ammonium sulfate or were incubated at 37 degrees C. After these treatments, a large proportion of the enzyme activity occurred in low (ca. 100,000) molecular weight regions. The low molecular weight phosphodiesterase activities from untreated, incubated, and trypsin-treated extracts possessed similar properties. All were inhibited by methylxanthines, had pH optima of approximately 8.0, and similar kinetic properties and requirements for divalent cations. These observations raise the possibility that preparative procedures or limited proteolysis occurring during preparation and handling of extracts can contribute to the apparent multiplicity of enzyme forms seen after gel filtration of phosphodiesterase from rat erythrocytes and perhaps other cell types."} {"id": "PMID:182575", "title": "Cyclic nucleotide phosphodiesterases, insulin and thyroid hormones.", "content": "The in vitro effects of insulin on different phosphodiesterase activities present in rat epididymal fat cells from normal and hypothyroid rats have been studied. Evidence is presented that insulin increases the maximum velocity of a particulate, low Km, cyclic adenosine-3', 5'-monophosphate (cyclic AMP) phosphodiesterase in both types of cells, this effect being more clearly evident with the fat cells from hypothyroid animals; combination of insulin and thyroidectomy resulted in a 400% stimulation with 10-10 - 10-9 M insulin. A clear and significant effect was apparent at 10-11 M insulin. However, the dose-response curve was biphasic, since stimulation by insulin was suppressed for doses of hormone higher 10-8 - 10-7 M. Moreover, insulin effects were very fast, since clear stimulation was observed after only 2 min of incubation; the maximal increase was obtained after 10 min. Insulin did not significantly affect the soluble cyclic AMP phosphodiesterase activity in normal cells, thus confirming results obtained by others. However, the soluble cyclic AMP phosphodiesterase activity was clearly stimulated by insulin when the fat cells were prepared from hypothyroid rats. Maximal stimulation was obtained with 10-9 M insulin; the response was again very fast. Soluble cyclic GMP phosphodiesterase activity was also increased additively by hypothyroidism and insulin, maximal stimulation being obtained with 10-9 M insulin. With this dose of insulin the additive effects of thyroidectomy and insulin produced a 5-fold stimulation. The effect of insulin on the soluble cyclic GMP phosphodiesterase was very fast (2-5 min). With both soluble cyclic nucleotide phosphodiesterase activities, insulin increased the maximal velocity but not apparent Km of the enzyme. Thus, hypothyroidism and insulin produced additive effects suggesting a different mechanism of action of these two hormonal situations on the degradation of the intracellular pools of cyclic AMP and cyclic GMP.", "contents": "Cyclic nucleotide phosphodiesterases, insulin and thyroid hormones. The in vitro effects of insulin on different phosphodiesterase activities present in rat epididymal fat cells from normal and hypothyroid rats have been studied. Evidence is presented that insulin increases the maximum velocity of a particulate, low Km, cyclic adenosine-3', 5'-monophosphate (cyclic AMP) phosphodiesterase in both types of cells, this effect being more clearly evident with the fat cells from hypothyroid animals; combination of insulin and thyroidectomy resulted in a 400% stimulation with 10-10 - 10-9 M insulin. A clear and significant effect was apparent at 10-11 M insulin. However, the dose-response curve was biphasic, since stimulation by insulin was suppressed for doses of hormone higher 10-8 - 10-7 M. Moreover, insulin effects were very fast, since clear stimulation was observed after only 2 min of incubation; the maximal increase was obtained after 10 min. Insulin did not significantly affect the soluble cyclic AMP phosphodiesterase activity in normal cells, thus confirming results obtained by others. However, the soluble cyclic AMP phosphodiesterase activity was clearly stimulated by insulin when the fat cells were prepared from hypothyroid rats. Maximal stimulation was obtained with 10-9 M insulin; the response was again very fast. Soluble cyclic GMP phosphodiesterase activity was also increased additively by hypothyroidism and insulin, maximal stimulation being obtained with 10-9 M insulin. With this dose of insulin the additive effects of thyroidectomy and insulin produced a 5-fold stimulation. The effect of insulin on the soluble cyclic GMP phosphodiesterase was very fast (2-5 min). With both soluble cyclic nucleotide phosphodiesterase activities, insulin increased the maximal velocity but not apparent Km of the enzyme. Thus, hypothyroidism and insulin produced additive effects suggesting a different mechanism of action of these two hormonal situations on the degradation of the intracellular pools of cyclic AMP and cyclic GMP."} {"id": "PMID:182576", "title": "Insect prothoracic glands: a role for cyclic AMP in the stimulation of alpha-ecdysone secretion.", "content": "The prothoracic glands of the tobacco hornworm, Manduca sexta, were studied to determine if cyclic AMP is involved in the regulation of alpha-ecdysone secretion. Culturing glands in the presence of the phosphodiesterase inhibitors, aminophylline and 1-methyl-3-isobutylxanthine, caused a greater than 2-fold stimulation of ecdysone secretion while cyclic AMP alone was ineffective. Based on a dose-response analysis, 1-methyl-3-isobutylxanthine was 200 times more potent than aminophylline. Measurements of endogenous prothoracic gland cyclic AMP during the fifth larval instar demonstrated that dramatically increased levels preceded the increase in in vitro ecdysone-secretory ability. The data suggest that cyclic AMP may act as a second messenger in the stimulation of prothoracic gland alpha-ecdysone secretion by the prothoracicotropic brain hormone.", "contents": "Insect prothoracic glands: a role for cyclic AMP in the stimulation of alpha-ecdysone secretion. The prothoracic glands of the tobacco hornworm, Manduca sexta, were studied to determine if cyclic AMP is involved in the regulation of alpha-ecdysone secretion. Culturing glands in the presence of the phosphodiesterase inhibitors, aminophylline and 1-methyl-3-isobutylxanthine, caused a greater than 2-fold stimulation of ecdysone secretion while cyclic AMP alone was ineffective. Based on a dose-response analysis, 1-methyl-3-isobutylxanthine was 200 times more potent than aminophylline. Measurements of endogenous prothoracic gland cyclic AMP during the fifth larval instar demonstrated that dramatically increased levels preceded the increase in in vitro ecdysone-secretory ability. The data suggest that cyclic AMP may act as a second messenger in the stimulation of prothoracic gland alpha-ecdysone secretion by the prothoracicotropic brain hormone."} {"id": "PMID:182577", "title": "Stabilization and characterization of the dexamethasone-binding proteins in rat liver cytosol.", "content": "Conditions were worked out for maximal stabilization of dexamethasone binding activity of rat liver cytosol in the absence of the protective steroid ligand. Important stabilization factors are ionic strength, thiol-protecting agents, glycerol and pH. Maximal stability of the cytosol is observed in a buffer consisting of 20 mM Tris-HCl, pH 7.5, 50 mM KCl, 25 mM beta-mercaptoethanol and 20% glycerol. Chromatography of cytosol on DEAE-cellulose revealed the existence of three dexamethasone receptors, binder DE-1, present in the flow-through fraction and binders DE-2 and DE-3, eluting from the column with salt concentrations of 100 and 190 mM, respectively. Binders DE-2 and DE-3 are not adsorbed on phosphocellulose at pH 7.5, whereas binder DE-1 is. All three receptors are retained to varying degrees on DNA-cellulose columns: binder DE-1 is eluted with salt concentrations of 270 mM, whereas binders DE-2 and DE-3 are eluted between 180 and 200 mM NaCl. The dexamethasone receptors also bind natural glucocorticoids, but to varying degrees, the highest binding being observed to binder DE-2. The receptors obtained after chromatography on DEAE-cellulose, but not on phosphocellulose, cannot be to an appreciable extent charged with dexamethasone.", "contents": "Stabilization and characterization of the dexamethasone-binding proteins in rat liver cytosol. Conditions were worked out for maximal stabilization of dexamethasone binding activity of rat liver cytosol in the absence of the protective steroid ligand. Important stabilization factors are ionic strength, thiol-protecting agents, glycerol and pH. Maximal stability of the cytosol is observed in a buffer consisting of 20 mM Tris-HCl, pH 7.5, 50 mM KCl, 25 mM beta-mercaptoethanol and 20% glycerol. Chromatography of cytosol on DEAE-cellulose revealed the existence of three dexamethasone receptors, binder DE-1, present in the flow-through fraction and binders DE-2 and DE-3, eluting from the column with salt concentrations of 100 and 190 mM, respectively. Binders DE-2 and DE-3 are not adsorbed on phosphocellulose at pH 7.5, whereas binder DE-1 is. All three receptors are retained to varying degrees on DNA-cellulose columns: binder DE-1 is eluted with salt concentrations of 270 mM, whereas binders DE-2 and DE-3 are eluted between 180 and 200 mM NaCl. The dexamethasone receptors also bind natural glucocorticoids, but to varying degrees, the highest binding being observed to binder DE-2. The receptors obtained after chromatography on DEAE-cellulose, but not on phosphocellulose, cannot be to an appreciable extent charged with dexamethasone."} {"id": "PMID:182578", "title": "Cholinergic regulation of cyclic nucleotide levels, amylase release, and K+ efflux from rat parotid glands.", "content": "Carbachol increased amylase release and K+ efflux from rat parotid tissue slices. The amount of amylase released was small compared to that released by isoproterenol. The effect of carbachol on amylase release and K+ efflux was a direct effect. This conclusion was based on the finding that the stimulatory effects of carbachol were blocked only by atropine and not by propanolol or phentolamine. In addition to the above effects, carbachol also caused a rapid increase in the parotid guanosine-3', 5' cyclic monophosphate (cGMP) levels without a discernable effect on adenosine-3',5' cyclic monophosphate (cAMP) levels. The increase in cGMP level caused by carbachol was blocked by atropine and not by phentolamine. The stimulatory effect of carbachol on amylase release was not additive with that of isoproterenol or dibutyryl cAMP. Although carbachol had no effect on basal cAMP levels it did inhibit increases in cAMP caused by isoproterenol. Similarly isoproterenol inhibited increased in parotid cGMP levels caused by carbachol. Unlike the apparent nonadditivity between the effects of isoproterenol and carbachol on amylase release and cAMP and cGMP accumulation, the effects on K+ efflux were additive. The possibility of a role for cGMP in mediating the effects of cholinergic agonists on K+ efflux was lessened by our observations that 1-methyl-3-isobutylxanthine enhanced the effect of limiting concentrations of carbachol on cGMP accumulation while not enhancing the effects of carbachol on K+ efflux.", "contents": "Cholinergic regulation of cyclic nucleotide levels, amylase release, and K+ efflux from rat parotid glands. Carbachol increased amylase release and K+ efflux from rat parotid tissue slices. The amount of amylase released was small compared to that released by isoproterenol. The effect of carbachol on amylase release and K+ efflux was a direct effect. This conclusion was based on the finding that the stimulatory effects of carbachol were blocked only by atropine and not by propanolol or phentolamine. In addition to the above effects, carbachol also caused a rapid increase in the parotid guanosine-3', 5' cyclic monophosphate (cGMP) levels without a discernable effect on adenosine-3',5' cyclic monophosphate (cAMP) levels. The increase in cGMP level caused by carbachol was blocked by atropine and not by phentolamine. The stimulatory effect of carbachol on amylase release was not additive with that of isoproterenol or dibutyryl cAMP. Although carbachol had no effect on basal cAMP levels it did inhibit increases in cAMP caused by isoproterenol. Similarly isoproterenol inhibited increased in parotid cGMP levels caused by carbachol. Unlike the apparent nonadditivity between the effects of isoproterenol and carbachol on amylase release and cAMP and cGMP accumulation, the effects on K+ efflux were additive. The possibility of a role for cGMP in mediating the effects of cholinergic agonists on K+ efflux was lessened by our observations that 1-methyl-3-isobutylxanthine enhanced the effect of limiting concentrations of carbachol on cGMP accumulation while not enhancing the effects of carbachol on K+ efflux."} {"id": "PMID:182583", "title": "Non-specific immunity after local immunization.", "content": "The most important advantage of local immunization is the non-specific effect. The active protection test in mice shows an immunity against oral infection with virulent Salmonella typhimurium bacteria after oral immunization with heterologous inactivated enterobacteria. We observed the same non-specific protection in a viral model. After oral immunization with inactivated S. typhimurium bacteria, the mice are protected against oral infection with a virulent parapoliomyelitis virus. In the phagocytosis test after local immunization a non-specific effect is also demonstrated. The rate of phagocytosis of macrophages against streptococci rises significantly after oral immunization or after inhalation with heat-killed S. typhimurium bacteria.", "contents": "Non-specific immunity after local immunization. The most important advantage of local immunization is the non-specific effect. The active protection test in mice shows an immunity against oral infection with virulent Salmonella typhimurium bacteria after oral immunization with heterologous inactivated enterobacteria. We observed the same non-specific protection in a viral model. After oral immunization with inactivated S. typhimurium bacteria, the mice are protected against oral infection with a virulent parapoliomyelitis virus. In the phagocytosis test after local immunization a non-specific effect is also demonstrated. The rate of phagocytosis of macrophages against streptococci rises significantly after oral immunization or after inhalation with heat-killed S. typhimurium bacteria."} {"id": "PMID:182579", "title": "Characteristics of the response of human adrenocortical cells to ACTH.", "content": "The effects of adrenocorticotrophic hormone (ACTH) on human adrenocortical steroidogenesis were studied in adrenocortical cells which had been isolated from normal and hyperplastic glands by a technique combining tyrpsin digestion and mechanical dispersion, and incubated in the presence of ACTH or dibutyryl cyclic AMP (dbcAMP). The response was measured in terms of cyclic AMP, cortisol, corticosterone, 11-deoxycortisol and cortisone production. A classical sigmoid curve, calculated by non-linear, least square method, related the increase in cAMP production or in steroidogenesis to the log dose of ACTH. For the normal adrenocortical cells, the estimated concentration of ACTH inducing a half-maximal response was approximated 2h0 pg ACTH 1-24/ml for steroidogenesis, against 437 pg/ml for cAMP production. The estimated Vmax (per 107 cells/ml, on average) was 27 pmol cAMP/2 and for steroidogenesis (in ng/2 h): 188 for cortisol, 106 for corticosterone, 37 for 11-deoxycortisol, and 32 for cortisone, dbcAMP (1.0 mM) stimulated steroidogenesis to a comparable extent. The cells from a hyperplastic adrenal gland exhibited a steroidogenic response to ACTH and dbcAMP which was 2-3 times greater than the response of a similar number of normal adrenocortical cells. Calculated per pmol cAMP generated, the ACTH-stimulated cortisol production by cells from hyperplastic gland was also increased with respect to normal cell response. These data suggest a prolonged effect of ACTH on cortisol biosynthetic pathway beyond the membrane step of cAMP generation.", "contents": "Characteristics of the response of human adrenocortical cells to ACTH. The effects of adrenocorticotrophic hormone (ACTH) on human adrenocortical steroidogenesis were studied in adrenocortical cells which had been isolated from normal and hyperplastic glands by a technique combining tyrpsin digestion and mechanical dispersion, and incubated in the presence of ACTH or dibutyryl cyclic AMP (dbcAMP). The response was measured in terms of cyclic AMP, cortisol, corticosterone, 11-deoxycortisol and cortisone production. A classical sigmoid curve, calculated by non-linear, least square method, related the increase in cAMP production or in steroidogenesis to the log dose of ACTH. For the normal adrenocortical cells, the estimated concentration of ACTH inducing a half-maximal response was approximated 2h0 pg ACTH 1-24/ml for steroidogenesis, against 437 pg/ml for cAMP production. The estimated Vmax (per 107 cells/ml, on average) was 27 pmol cAMP/2 and for steroidogenesis (in ng/2 h): 188 for cortisol, 106 for corticosterone, 37 for 11-deoxycortisol, and 32 for cortisone, dbcAMP (1.0 mM) stimulated steroidogenesis to a comparable extent. The cells from a hyperplastic adrenal gland exhibited a steroidogenic response to ACTH and dbcAMP which was 2-3 times greater than the response of a similar number of normal adrenocortical cells. Calculated per pmol cAMP generated, the ACTH-stimulated cortisol production by cells from hyperplastic gland was also increased with respect to normal cell response. These data suggest a prolonged effect of ACTH on cortisol biosynthetic pathway beyond the membrane step of cAMP generation."} {"id": "PMID:182580", "title": "Similarity of responses of cultured Sertoli cells to cholera toxin and FSH.", "content": "The effects of cholera toxin on the responses of cultured Sertoli cells were compared with those elicited by follicle-stimulating hormone (FSH), and N6O2'-dibutyryl-3',5'-cyclic AMP (bu2cAMP). Addition of FSH or cholera toxin increased cAMP levels. Subsequently there was greater rates of conversion of testosterone to 17beta-estradiol, formation of androgen-binding protein (ABP), and incorporation of [3H]thymidine into DNA by Sertoli cells prepared from testes of immature rats and cultured in the presence of either FSH or cholera toxin. Addition of bu2-cAMP also resulted in enhanced rates of formation of ABP, synthesis of 17beta-estradiol and synthesis of DNA. Cholera toxin and bu2-cAMP elicited changes in morphology of cultured Sertoli cells indistinguishable from those following FSH addition. It is concluded that elevated intracellular cAMP levels can duplicate known actions of FSH on cultured Sertoli cells, but the possible obligatory role of cAMP in mediating FSH actions remains to be evaluated.", "contents": "Similarity of responses of cultured Sertoli cells to cholera toxin and FSH. The effects of cholera toxin on the responses of cultured Sertoli cells were compared with those elicited by follicle-stimulating hormone (FSH), and N6O2'-dibutyryl-3',5'-cyclic AMP (bu2cAMP). Addition of FSH or cholera toxin increased cAMP levels. Subsequently there was greater rates of conversion of testosterone to 17beta-estradiol, formation of androgen-binding protein (ABP), and incorporation of [3H]thymidine into DNA by Sertoli cells prepared from testes of immature rats and cultured in the presence of either FSH or cholera toxin. Addition of bu2-cAMP also resulted in enhanced rates of formation of ABP, synthesis of 17beta-estradiol and synthesis of DNA. Cholera toxin and bu2-cAMP elicited changes in morphology of cultured Sertoli cells indistinguishable from those following FSH addition. It is concluded that elevated intracellular cAMP levels can duplicate known actions of FSH on cultured Sertoli cells, but the possible obligatory role of cAMP in mediating FSH actions remains to be evaluated."} {"id": "PMID:182584", "title": "Oral immunization against pox. Studies on fowl pox as a model.", "content": "Oral vaccination against fowl pox is both effective and harmless. A suitable vaccine strain is the attenuated HP-1 strain in the 200th to 400th tissue culture passage. For optimal immunization virus of the 200th to 270th passage level should be applied twice at an interval of 3 to 4 weeks. Vaccination dose should contain 10(7.0)TCID50. Chickens may be effectively immunized already at 5 days. Immunity is against both homologous and heterologous virus and proves equally resistant to oral, cutaneous and intravenous challenge. Protection of mucous membranes of the upper respiratory and digestive tract forms faster than after cutaneous immunization. Compared to conventional fowl pox vaccination, drinking water vaccination facilitates the technicalities of vaccination; there are immunological advantages and risks of complications are avoided. It can therefore be recommended as a model for vaccination against smallpox in man.", "contents": "Oral immunization against pox. Studies on fowl pox as a model. Oral vaccination against fowl pox is both effective and harmless. A suitable vaccine strain is the attenuated HP-1 strain in the 200th to 400th tissue culture passage. For optimal immunization virus of the 200th to 270th passage level should be applied twice at an interval of 3 to 4 weeks. Vaccination dose should contain 10(7.0)TCID50. Chickens may be effectively immunized already at 5 days. Immunity is against both homologous and heterologous virus and proves equally resistant to oral, cutaneous and intravenous challenge. Protection of mucous membranes of the upper respiratory and digestive tract forms faster than after cutaneous immunization. Compared to conventional fowl pox vaccination, drinking water vaccination facilitates the technicalities of vaccination; there are immunological advantages and risks of complications are avoided. It can therefore be recommended as a model for vaccination against smallpox in man."} {"id": "PMID:182581", "title": "Hormonal control of cyclic AMP turnover in isolated fat cells.", "content": "Control of the levels of cAMP in the early phase after addition of catecholamines and the effect of insulin is discussed under consideration of own findings from experiments with isolated fat cells of the rat. Data on the kinetics of cAMP are interpreted in the light of results from several groups of a rapid activation of phosphodiesterase activity along with the adenylate cyclase system. Comparison of energy metabolism of fat cells with the formation of cAMP under conditions of near-maximal activation of the adenylate cyclase system by isoproterenol shows that about half of the cellular ATP turnover is used for information transfer. Insulin reduces cAMP concentrations in the presence of isoproterenol within one min of incubation when added either together with or after the catecholamine. Experiments with propranolol and the phosphodiesterase inhibitor, methyl isobutylxanthine suggest an effect of insulin on formation and breakdown of cAMP.", "contents": "Hormonal control of cyclic AMP turnover in isolated fat cells. Control of the levels of cAMP in the early phase after addition of catecholamines and the effect of insulin is discussed under consideration of own findings from experiments with isolated fat cells of the rat. Data on the kinetics of cAMP are interpreted in the light of results from several groups of a rapid activation of phosphodiesterase activity along with the adenylate cyclase system. Comparison of energy metabolism of fat cells with the formation of cAMP under conditions of near-maximal activation of the adenylate cyclase system by isoproterenol shows that about half of the cellular ATP turnover is used for information transfer. Insulin reduces cAMP concentrations in the presence of isoproterenol within one min of incubation when added either together with or after the catecholamine. Experiments with propranolol and the phosphodiesterase inhibitor, methyl isobutylxanthine suggest an effect of insulin on formation and breakdown of cAMP."} {"id": "PMID:182585", "title": "Oral immunization against smallpox.", "content": "Attenuated vaccinia strain penetrates the mucous membranes of the oral and pharyngeal cavity; local lesions are not produced, even if high doses of attenuated virus are applied. Attenuated vaccinia virus thus offers the possibility of oral and nasal immunization against smallpox in man. Several groups of monkeys were immunized by the oral and nasal route. The subsequent challenge with virulent smallpox virus resulted in strongly mitigated clinical symptoms as compared to non-immunized controls. In the human, oral immunization with live attenuated virus was affected by the administration of virus-containing tablets. The procedures caused no untoward effect in primary vaccinees. Subsequent skin testing and conventional cutaneous vaccination resulted in accelerated takes, demonstrating successful oral pre-immunization.", "contents": "Oral immunization against smallpox. Attenuated vaccinia strain penetrates the mucous membranes of the oral and pharyngeal cavity; local lesions are not produced, even if high doses of attenuated virus are applied. Attenuated vaccinia virus thus offers the possibility of oral and nasal immunization against smallpox in man. Several groups of monkeys were immunized by the oral and nasal route. The subsequent challenge with virulent smallpox virus resulted in strongly mitigated clinical symptoms as compared to non-immunized controls. In the human, oral immunization with live attenuated virus was affected by the administration of virus-containing tablets. The procedures caused no untoward effect in primary vaccinees. Subsequent skin testing and conventional cutaneous vaccination resulted in accelerated takes, demonstrating successful oral pre-immunization."} {"id": "PMID:182582", "title": "A synergistic effect of androgen on the stimulation of progesterone secretion by FSH in cultured rat granulosa cells.", "content": "Granulosa cells from preovulatory follicles (PO) or from the enlarged preantral follicles of hypophysectomized immature diethylstilbestrol-treated (Hx-DES) rats were cultured with various combinations of FSH, androst-4-ene-3,17-dione (Ad), estradiol-17beta and dibutyryl cyclic AMP (dbcAMP). Progestin levels (progesterone and 20alpha-dihydroprogesterone) in the medium after 2 days of culture were assayed by radioimmunoassay. The control levels of the two progestins were lower for Hx-DES than for PO cells. Rat FSH (NIAMD-1-3;0.1 mug/ml) caused a 2-fold rise in progestin accumulation in both PO and Hx-DES cultures, dbcAMP (1 mM) increased progestin accumulation in PO cultures 4-5-fold, and to an even greater extent (10-20 fold) in Hx-DES cultures. Androstenedione (1.0 mug/ml) augmented progestin accumulation (1.5-3-fold), and synergized the steroidogenic action of FSH: in cells from Hx-DES rats, combined treatment with FSH and Ad caused a 5-10-fold increase over the values obtained with FSH alone. Testosterone and 5alpha-dihydrotestosterone, but not estradiol-17beta or estrone, mimicked these effects of Ad, Ad did not synergize the action of dbcAMP on progestin levels in Hx-DES cultures. It is proposed that androgen may play a role in the development of the FSH-responsive mechanism in preantral granulosa cells.", "contents": "A synergistic effect of androgen on the stimulation of progesterone secretion by FSH in cultured rat granulosa cells. Granulosa cells from preovulatory follicles (PO) or from the enlarged preantral follicles of hypophysectomized immature diethylstilbestrol-treated (Hx-DES) rats were cultured with various combinations of FSH, androst-4-ene-3,17-dione (Ad), estradiol-17beta and dibutyryl cyclic AMP (dbcAMP). Progestin levels (progesterone and 20alpha-dihydroprogesterone) in the medium after 2 days of culture were assayed by radioimmunoassay. The control levels of the two progestins were lower for Hx-DES than for PO cells. Rat FSH (NIAMD-1-3;0.1 mug/ml) caused a 2-fold rise in progestin accumulation in both PO and Hx-DES cultures, dbcAMP (1 mM) increased progestin accumulation in PO cultures 4-5-fold, and to an even greater extent (10-20 fold) in Hx-DES cultures. Androstenedione (1.0 mug/ml) augmented progestin accumulation (1.5-3-fold), and synergized the steroidogenic action of FSH: in cells from Hx-DES rats, combined treatment with FSH and Ad caused a 5-10-fold increase over the values obtained with FSH alone. Testosterone and 5alpha-dihydrotestosterone, but not estradiol-17beta or estrone, mimicked these effects of Ad, Ad did not synergize the action of dbcAMP on progestin levels in Hx-DES cultures. It is proposed that androgen may play a role in the development of the FSH-responsive mechanism in preantral granulosa cells."} {"id": "PMID:182586", "title": "Local immunity in Newcastle disease: some recent experiments.", "content": "Following primary exposure by the ocular route to lentogenic Newcastle disease virus (NDV) the lacrymal fluid, saliva and tracheal washes of three-week old specific pathogen free chickens acquired specific virus-neutralizing activity which considerably exceeded transudation of circulating antibody. All three secretions contain IgA which, at least in saliva, accounted for 85% of its activity, the remanider being due to IgG. Antibody in secretions limited, but did not prevent, reinfection of the trachea when birds were challenged two weeks later. In contrast to an elevation of circulating antibody titre, challenge induced only a repeated primary response in secreted antibody. Ocular infection induced marked lymphoid and plasma cell activity in the Harderian gland which is a major source of specific antibody in lachrymal and possibly other fluids. Functional ablation of the gland can be effected by occlusion of its draining duct, providing a means for evaluation of its immunological significance.", "contents": "Local immunity in Newcastle disease: some recent experiments. Following primary exposure by the ocular route to lentogenic Newcastle disease virus (NDV) the lacrymal fluid, saliva and tracheal washes of three-week old specific pathogen free chickens acquired specific virus-neutralizing activity which considerably exceeded transudation of circulating antibody. All three secretions contain IgA which, at least in saliva, accounted for 85% of its activity, the remanider being due to IgG. Antibody in secretions limited, but did not prevent, reinfection of the trachea when birds were challenged two weeks later. In contrast to an elevation of circulating antibody titre, challenge induced only a repeated primary response in secreted antibody. Ocular infection induced marked lymphoid and plasma cell activity in the Harderian gland which is a major source of specific antibody in lachrymal and possibly other fluids. Functional ablation of the gland can be effected by occlusion of its draining duct, providing a means for evaluation of its immunological significance."} {"id": "PMID:182587", "title": "The proposed international standard for infectious bronchitis vaccine (live).", "content": "An H-120 strain of infectious bronchitis virus was prepared in a form suitable to serve as an international standard for Infectious Bronchitis Vaccine (live). Accelerated degradation studies carried out on this vaccine showed it to be of suitable stability to serve as a standard. Results from a collaborative assay involving ten laboratories demonstrated that the proposed standard reduced the variation in virus titrations both within and between laboratories. This assay also showed that firstly the proposed standard could be used as a reference vaccine for the different safety tests described by the collaborating laboratories, and secondly as a reference vaccine in the different potency tests.", "contents": "The proposed international standard for infectious bronchitis vaccine (live). An H-120 strain of infectious bronchitis virus was prepared in a form suitable to serve as an international standard for Infectious Bronchitis Vaccine (live). Accelerated degradation studies carried out on this vaccine showed it to be of suitable stability to serve as a standard. Results from a collaborative assay involving ten laboratories demonstrated that the proposed standard reduced the variation in virus titrations both within and between laboratories. This assay also showed that firstly the proposed standard could be used as a reference vaccine for the different safety tests described by the collaborating laboratories, and secondly as a reference vaccine in the different potency tests."} {"id": "PMID:182588", "title": "Studies on vaccination against infectious laryngotracheitis by the drinking water.", "content": "The authors, after a brief reference to the wide use in the field of a mild vaccinal strain of infectious laryngotracheitis virus by the drinking water to prevent the disease, describe laboratory experiments to confirm the efficacy of this route of administration compared with the conventional one (ocular). Four groups of 7-week-old chickens were vaccinated as follows: a) ocularly with the normal dose, b)by instillation per os, c) by the drinking water with one dose, d) by the same route with ten doses; a fifth group was left as negative control. To compare the effect of vaccination by the above different methods of administration the serum-neutralization test was used. The results obtained are finally discussed.", "contents": "Studies on vaccination against infectious laryngotracheitis by the drinking water. The authors, after a brief reference to the wide use in the field of a mild vaccinal strain of infectious laryngotracheitis virus by the drinking water to prevent the disease, describe laboratory experiments to confirm the efficacy of this route of administration compared with the conventional one (ocular). Four groups of 7-week-old chickens were vaccinated as follows: a) ocularly with the normal dose, b)by instillation per os, c) by the drinking water with one dose, d) by the same route with ten doses; a fifth group was left as negative control. To compare the effect of vaccination by the above different methods of administration the serum-neutralization test was used. The results obtained are finally discussed."} {"id": "PMID:182589", "title": "Vaccination by the non-parenteral route of virus disease in the veterinary field.", "content": "After a brief reference to the importance of the non-parenteral route of vaccination of domestic animals in general, the author deals, for each animal species separately, with the most important vaccines utilised by this method of administration. On the basis of bibliographical data, he describes the history of this use, discusses the results of the application in the field and draws the relative conclusions.", "contents": "Vaccination by the non-parenteral route of virus disease in the veterinary field. After a brief reference to the importance of the non-parenteral route of vaccination of domestic animals in general, the author deals, for each animal species separately, with the most important vaccines utilised by this method of administration. On the basis of bibliographical data, he describes the history of this use, discusses the results of the application in the field and draws the relative conclusions."} {"id": "PMID:182590", "title": "Comparative tests on safety and potency of IBA vaccines.", "content": "During a comparative test on the pathogenicity and immunogenicity of a non-adapted and an embryo-adapted IDA virus, following observations were made: 1) the non-adapted virus remained pathogenic as determined by weight loss and bursal lesions. Clinical signs and mortality did not occur. A change in the virulence did not occur during back passages; 2) the immunosuppressive effect of the non-adapted virus was diminished by maternal antibodies; 3) the embryo-adapted virus produced little pathogenicity as demonstrated by minor weight depressions. The vaccinated birds had no recognizable pathological lesions in the bursae. Immunosuppression with this virus was not observed; 4) the embryo-adapted strain was able to induce neutralizing antibodies in birds with or without maternal antibodies. However, precipitins were not detected; 5) immunization with the embryo-adapted strain after 8 days of age was protective whereas prior to that age it was not confirming the age susceptibility factor reported by Hitchner (1971); 6) no change in virulence occurred during back passages with both test materials.", "contents": "Comparative tests on safety and potency of IBA vaccines. During a comparative test on the pathogenicity and immunogenicity of a non-adapted and an embryo-adapted IDA virus, following observations were made: 1) the non-adapted virus remained pathogenic as determined by weight loss and bursal lesions. Clinical signs and mortality did not occur. A change in the virulence did not occur during back passages; 2) the immunosuppressive effect of the non-adapted virus was diminished by maternal antibodies; 3) the embryo-adapted virus produced little pathogenicity as demonstrated by minor weight depressions. The vaccinated birds had no recognizable pathological lesions in the bursae. Immunosuppression with this virus was not observed; 4) the embryo-adapted strain was able to induce neutralizing antibodies in birds with or without maternal antibodies. However, precipitins were not detected; 5) immunization with the embryo-adapted strain after 8 days of age was protective whereas prior to that age it was not confirming the age susceptibility factor reported by Hitchner (1971); 6) no change in virulence occurred during back passages with both test materials."} {"id": "PMID:182591", "title": "Infectious bursal disease vaccine: some remarks on production and control.", "content": "A vaccine against infectious bursal disease (IBD) is prepared with a strain of IBD virus attenuated in chicken embryos. Safety and potency tests are carried out on embryos and chickens susceptible to IBD virus.", "contents": "Infectious bursal disease vaccine: some remarks on production and control. A vaccine against infectious bursal disease (IBD) is prepared with a strain of IBD virus attenuated in chicken embryos. Safety and potency tests are carried out on embryos and chickens susceptible to IBD virus."} {"id": "PMID:182592", "title": "Standard requirements for vaccines against infectious bursal disease.", "content": "A variety of criteria must be considered when examining the suitability of preparations of live infectious bursal disease (IBD) virus for use as vaccines: identity and purity of the vaccine strain, lack of spread, or of tendency to revert to virulence, lack of immunosuppressive effect, safety and potency. Arguments as to th identity of IBD virus are well documented, and after ensuring that the virus strain is in fact IBD virus, it must be ascertained that it is free from contaminating agents. If the vaccine strain spreads, lack of reversion to virulence must be determined by several direct chick to chick passages: histological observations of bursae from first and final passages must be made to ensure that no change has occurred. In order to formulate proposals for standard tests of safety, lack of immunosuppressive effect and potency for IBD vaccines, comparative studies were made of products of different origins. Safety of the vaccines was assessed by observing young chicks after administration and measuring loss in weight gain. The effect on the bursa was judged by weighing and making microscopic observations at intervals. The immunosuppressive effect of the vaccines was assessed by comparing the serological and protective responses to subsequent Newcastle disease (ND) vaccination with the response in chicks given no IBD vaccine. Potency of the vaccines was determined by challenge of vaccinated chicks with virulent IBD virus. Various properties were found in the products examined. Some were concluded to be insufficiently attenuated because of the effect on the bird or upon its bursa and the consequent effect on the bird's immune competence. The ability to confer protection was not correlated with the degree of damage caused in the bursa. Vaccines which had no adverse effect on the health of the bird, caused little or no damage to the bursa and conferred adequate protection against challenge were considered to be of a satisfactory standard.", "contents": "Standard requirements for vaccines against infectious bursal disease. A variety of criteria must be considered when examining the suitability of preparations of live infectious bursal disease (IBD) virus for use as vaccines: identity and purity of the vaccine strain, lack of spread, or of tendency to revert to virulence, lack of immunosuppressive effect, safety and potency. Arguments as to th identity of IBD virus are well documented, and after ensuring that the virus strain is in fact IBD virus, it must be ascertained that it is free from contaminating agents. If the vaccine strain spreads, lack of reversion to virulence must be determined by several direct chick to chick passages: histological observations of bursae from first and final passages must be made to ensure that no change has occurred. In order to formulate proposals for standard tests of safety, lack of immunosuppressive effect and potency for IBD vaccines, comparative studies were made of products of different origins. Safety of the vaccines was assessed by observing young chicks after administration and measuring loss in weight gain. The effect on the bursa was judged by weighing and making microscopic observations at intervals. The immunosuppressive effect of the vaccines was assessed by comparing the serological and protective responses to subsequent Newcastle disease (ND) vaccination with the response in chicks given no IBD vaccine. Potency of the vaccines was determined by challenge of vaccinated chicks with virulent IBD virus. Various properties were found in the products examined. Some were concluded to be insufficiently attenuated because of the effect on the bird or upon its bursa and the consequent effect on the bird's immune competence. The ability to confer protection was not correlated with the degree of damage caused in the bursa. Vaccines which had no adverse effect on the health of the bird, caused little or no damage to the bursa and conferred adequate protection against challenge were considered to be of a satisfactory standard."} {"id": "PMID:182593", "title": "The epizootiology of infectious bursal disease and prevention of it by immunization.", "content": "Transport of leftover feed from infectious disease (IBD) farms to susceptible flocks on clean premises is believed to have played an important role in the transmission of this disease to new farms and to new areas. Servicemen, caretakers, contaminated equipment and air were suspected in the spread of the disease, but these modes were not demonstrated. Litter, drinking water and samples of feed from feeders of IBD flocks were found to be infectious when added to rations of susceptible chickens but were not when added to drinking water. Infectious bursal agent (IBA) remained viable for at least 6 months in dry litter and in unused dry chicken houses for more than 1 year. IBA was found in circulating blood of infected chickens 36 hours after inoculation, but not after 72 hours. Liver, spleen, thymus, kidney, pancreas and intestines were infectious at 72 hours. Bursa and feces were infectious from 48 hours through 7 days after inoculation. Tests on 4 1/2 to 6-week-old birds from 10-12 farms of each of several broiler complexes in three southeastern states of the U.S. revealed IBA present on a high percentage of farms even though none had used vaccine. Vaccination with modified or unmodified IBA administered to millions of 4-10-day-old chicks gave good protection for the life of broilers and laying birds. Effect of IBD on development of immunity to other diseases will be discussed.", "contents": "The epizootiology of infectious bursal disease and prevention of it by immunization. Transport of leftover feed from infectious disease (IBD) farms to susceptible flocks on clean premises is believed to have played an important role in the transmission of this disease to new farms and to new areas. Servicemen, caretakers, contaminated equipment and air were suspected in the spread of the disease, but these modes were not demonstrated. Litter, drinking water and samples of feed from feeders of IBD flocks were found to be infectious when added to rations of susceptible chickens but were not when added to drinking water. Infectious bursal agent (IBA) remained viable for at least 6 months in dry litter and in unused dry chicken houses for more than 1 year. IBA was found in circulating blood of infected chickens 36 hours after inoculation, but not after 72 hours. Liver, spleen, thymus, kidney, pancreas and intestines were infectious at 72 hours. Bursa and feces were infectious from 48 hours through 7 days after inoculation. Tests on 4 1/2 to 6-week-old birds from 10-12 farms of each of several broiler complexes in three southeastern states of the U.S. revealed IBA present on a high percentage of farms even though none had used vaccine. Vaccination with modified or unmodified IBA administered to millions of 4-10-day-old chicks gave good protection for the life of broilers and laying birds. Effect of IBD on development of immunity to other diseases will be discussed."} {"id": "PMID:182594", "title": "Oral immunization of ducklings with attenuated duck hepatitis virus.", "content": "Duck hepatitis, a highly fatal disease of ducklings, must be controlled in successful commercial duck enterprises. Several procedures which have been effective in controlling the disease are 1) vaccination of adult breeders with passive transfer of antibodies through the yolk to the duckling, 2) administration of antisera to ducklings at the onset of signs of disease, and 3) parenteral vaccination of ducklings with attenuated DH virus after the loss of passive immunity. However, in each of these procedures, some losses usually occur and the administration of antiserum or vaccine to 2- to 3-week-old ducklings is costly and involves physical stress. Experimental studies of oral immunization in ducklings from immunized and nonimmunized parents were conducted to determine the feasibility of a convenient control program with little stress to the ducklings. Ducklings immunized with attenuated live duck hepatitis virus by intramuscular method, oral instillation, and through the drinking water were challenged with virulent duck hepatitis virus either intramuscularly or orally. Intramuscular, oral instillation, and drinking water application all provided adequate protection on challenge with virulent virus. Rise in neutralizing antibody was detected following immunization especially in sera of ducklings from nonimmunized parents. On the basis of successful experimental results, over 350,000 ducklings from immunized parents on a commercial farm have been sucessfully vaccinated by the drinking water method.", "contents": "Oral immunization of ducklings with attenuated duck hepatitis virus. Duck hepatitis, a highly fatal disease of ducklings, must be controlled in successful commercial duck enterprises. Several procedures which have been effective in controlling the disease are 1) vaccination of adult breeders with passive transfer of antibodies through the yolk to the duckling, 2) administration of antisera to ducklings at the onset of signs of disease, and 3) parenteral vaccination of ducklings with attenuated DH virus after the loss of passive immunity. However, in each of these procedures, some losses usually occur and the administration of antiserum or vaccine to 2- to 3-week-old ducklings is costly and involves physical stress. Experimental studies of oral immunization in ducklings from immunized and nonimmunized parents were conducted to determine the feasibility of a convenient control program with little stress to the ducklings. Ducklings immunized with attenuated live duck hepatitis virus by intramuscular method, oral instillation, and through the drinking water were challenged with virulent duck hepatitis virus either intramuscularly or orally. Intramuscular, oral instillation, and drinking water application all provided adequate protection on challenge with virulent virus. Rise in neutralizing antibody was detected following immunization especially in sera of ducklings from nonimmunized parents. On the basis of successful experimental results, over 350,000 ducklings from immunized parents on a commercial farm have been sucessfully vaccinated by the drinking water method."} {"id": "PMID:182595", "title": "Vaccination against avian encephalomyelitis with special reference to the spray method.", "content": "Three vaccination methods against avian encephalomyelitis have been tested in different types of housing. The product used was a vaccine improved by Philips-Duphar, having an optimal disseminative and immunogenic capacity, and a high virus titer per bird dose. We have tested: 1) administration per os in 2-5% of the flock, 2) administration via drinking water in the whole flock and 3) spray vaccination. Observations by Schneider (1967), that administration in the beak in part of the animals may only be satisfactory under optimal conditions, have herewith been confirmed. With the actual rearing on batteries, the chance of horizontal spreading of the vaccine virus is minimal. The two other methods of administration eliminate this problem. Already 3 weeks after vaccination more than 50% of the animals show a positive serological reaction. Later this level increases quickly to more than 80%, even in batteries. Under widely varying circumstances (concentaration of animals, ventilation, length of water tubes, etc) a dosage response effect becomes apparent. The practical results obtainable will be dependent on the titer of the vaccine, care while vaccinating and conditions of housing.", "contents": "Vaccination against avian encephalomyelitis with special reference to the spray method. Three vaccination methods against avian encephalomyelitis have been tested in different types of housing. The product used was a vaccine improved by Philips-Duphar, having an optimal disseminative and immunogenic capacity, and a high virus titer per bird dose. We have tested: 1) administration per os in 2-5% of the flock, 2) administration via drinking water in the whole flock and 3) spray vaccination. Observations by Schneider (1967), that administration in the beak in part of the animals may only be satisfactory under optimal conditions, have herewith been confirmed. With the actual rearing on batteries, the chance of horizontal spreading of the vaccine virus is minimal. The two other methods of administration eliminate this problem. Already 3 weeks after vaccination more than 50% of the animals show a positive serological reaction. Later this level increases quickly to more than 80%, even in batteries. Under widely varying circumstances (concentaration of animals, ventilation, length of water tubes, etc) a dosage response effect becomes apparent. The practical results obtainable will be dependent on the titer of the vaccine, care while vaccinating and conditions of housing."} {"id": "PMID:182596", "title": "Application of the turkey herpesvirus vaccine by the aerogenic route for the prevention of Marek's disease.", "content": "Recently in laboratory and field trials, birds were vaccinated with cell-free HVT vaccine by aerosol spray. In laboratory trials, birds vaccinated by aerosol spray were as well protected against challenge with virulent MD (GA isolate) as those vaccinated by subcutaneous inoculation. Birds were vaccinated with a sprayer (Spraying Systems Company, Wheaton, Illinois) which emits a particle size in which 90% are less than microns. The chicks were sprayed with 1,000 to 10,000 PFU per bird dose and remained in contact with the aerosol for 30-60 min. Turkey herpesvirus was isolated from the blood or kidney of these birds as early as 7 to 10 days postvaccination. In field trials approximately 300,000 birds have been vaccinated by aerosol spray with between 2,000 to 5, 000 PFU of cell-free HVT vaccine per chick. Chicks were sprayed while they were in the trays of the hatchers which still contained the dust and down which remained after hatching. Prior to spraying, the incoming and outgoing aid ducts were closed. The chicks were sprayed for 12-15 min with 250-300 ml of diluent, and after completion of spraying the chicks remained in contact with tha aerosol for an additional 5 to 8 min. In the birds vaccinated by aerosol spray the incidence of MD in the processing plant varied from 0.0% to 23.4%, while the incidence of MD in birds vaccinated by subcutaneous inoculation varied from 0.02 to 23.9%. Overall the incidence of MD in birds vaccinated by aerosol spray was essentially the same as those vaccinated by subcutaneous inoculation.", "contents": "Application of the turkey herpesvirus vaccine by the aerogenic route for the prevention of Marek's disease. Recently in laboratory and field trials, birds were vaccinated with cell-free HVT vaccine by aerosol spray. In laboratory trials, birds vaccinated by aerosol spray were as well protected against challenge with virulent MD (GA isolate) as those vaccinated by subcutaneous inoculation. Birds were vaccinated with a sprayer (Spraying Systems Company, Wheaton, Illinois) which emits a particle size in which 90% are less than microns. The chicks were sprayed with 1,000 to 10,000 PFU per bird dose and remained in contact with the aerosol for 30-60 min. Turkey herpesvirus was isolated from the blood or kidney of these birds as early as 7 to 10 days postvaccination. In field trials approximately 300,000 birds have been vaccinated by aerosol spray with between 2,000 to 5, 000 PFU of cell-free HVT vaccine per chick. Chicks were sprayed while they were in the trays of the hatchers which still contained the dust and down which remained after hatching. Prior to spraying, the incoming and outgoing aid ducts were closed. The chicks were sprayed for 12-15 min with 250-300 ml of diluent, and after completion of spraying the chicks remained in contact with tha aerosol for an additional 5 to 8 min. In the birds vaccinated by aerosol spray the incidence of MD in the processing plant varied from 0.0% to 23.4%, while the incidence of MD in birds vaccinated by subcutaneous inoculation varied from 0.02 to 23.9%. Overall the incidence of MD in birds vaccinated by aerosol spray was essentially the same as those vaccinated by subcutaneous inoculation."} {"id": "PMID:182597", "title": "Immunity studies in calves vaccinated with a multivalent live respiratory vaccine composed of I.B.R., parainfluenza 3 and bovine adenovirus type 3.", "content": "The persistence of systemic and local antibodies was studied after two intranasal administrations of the vaccine, six weeks apart. Systemic antibodies to I.B.R. and adenovirus 3 evoked by the vaccine were still present 21 weeks following the second dose of the vaccine. Inconslusive results were obtained regarding the persistence of systemic and local PI-3 antibodies because of an intercurrent natureal PI-3 infection occurring during the observation period. Local antibodies to adenovirus type 3 were found in a high percentage of vaccinated animals 21 weeks after the second dose of the vaccine, whereas local antibodies to I.B.R. remained detectable in 50% of the animals eight weeks after thesecond dose. The results of a challenge study 21 weeks after revaccination show that the presence of local and systemic antibodies prevent the multiplication of PI-3 and BAV-3 in the upper respiratory tract. Protection against I.B.R. was achieved in the absence of detectable local antibodies.", "contents": "Immunity studies in calves vaccinated with a multivalent live respiratory vaccine composed of I.B.R., parainfluenza 3 and bovine adenovirus type 3. The persistence of systemic and local antibodies was studied after two intranasal administrations of the vaccine, six weeks apart. Systemic antibodies to I.B.R. and adenovirus 3 evoked by the vaccine were still present 21 weeks following the second dose of the vaccine. Inconslusive results were obtained regarding the persistence of systemic and local PI-3 antibodies because of an intercurrent natureal PI-3 infection occurring during the observation period. Local antibodies to adenovirus type 3 were found in a high percentage of vaccinated animals 21 weeks after the second dose of the vaccine, whereas local antibodies to I.B.R. remained detectable in 50% of the animals eight weeks after thesecond dose. The results of a challenge study 21 weeks after revaccination show that the presence of local and systemic antibodies prevent the multiplication of PI-3 and BAV-3 in the upper respiratory tract. Protection against I.B.R. was achieved in the absence of detectable local antibodies."} {"id": "PMID:182598", "title": "Further studies on the neonatal ferret model of infection and immunity to and attenuation of human parainfluenza viruses.", "content": "Earlier we reported on the susceptibility via the intranasal route of inoculation of newborn ferrets to infection by wild and serially egg passaged parainfluenza type 3 virus. The wild type consistently induced fatal infection whereas with serial egg passage, mortality rate decreased while the degree of infectivity remained the same. This attenuation was accompanied by a change in capacity to induce interferon and decreased growth in human and primate cell cultures. The present work reports, similarly, on the susceptibility of newborn ferrets to wild and serially egg passaged parainfluenza types 1 and 2. Wild type infections caused significantly greater mortality than did egg passaged materials, although infectivity rates were approximately the same. Wild and egg passaged strains produced silent infections in adult ferrets and induced specific circulating hemagglutinin inhibiting antibodies. Newborn offspring of dams inoculated with wild or egg passaged viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage was correlated with alteration in cell culture host range and capacity to induce interferon. The low and mid level passages of types 1 and 3 were the subject of clinical vaccination trials in man in four age groups: 18-35 years, 14-16 years and 6-12 years. The clinical and serologic results of these studies will be reported elsewhere.", "contents": "Further studies on the neonatal ferret model of infection and immunity to and attenuation of human parainfluenza viruses. Earlier we reported on the susceptibility via the intranasal route of inoculation of newborn ferrets to infection by wild and serially egg passaged parainfluenza type 3 virus. The wild type consistently induced fatal infection whereas with serial egg passage, mortality rate decreased while the degree of infectivity remained the same. This attenuation was accompanied by a change in capacity to induce interferon and decreased growth in human and primate cell cultures. The present work reports, similarly, on the susceptibility of newborn ferrets to wild and serially egg passaged parainfluenza types 1 and 2. Wild type infections caused significantly greater mortality than did egg passaged materials, although infectivity rates were approximately the same. Wild and egg passaged strains produced silent infections in adult ferrets and induced specific circulating hemagglutinin inhibiting antibodies. Newborn offspring of dams inoculated with wild or egg passaged viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage was correlated with alteration in cell culture host range and capacity to induce interferon. The low and mid level passages of types 1 and 3 were the subject of clinical vaccination trials in man in four age groups: 18-35 years, 14-16 years and 6-12 years. The clinical and serologic results of these studies will be reported elsewhere."} {"id": "PMID:182599", "title": "Intranasal vaccination of cattle against IBR and PI3: field and laboratory observations in dairy, beef, and neonatal calf populations.", "content": "The author first summarizes the development of intranasal vaccination by Nasalgen P and particularly Nasalgen IP, previously reported, and then reviews present knowledge regarding safety and efficacy of Nasalgen IP in feeder calves, dairy animals and neonates. The minimal immunogenic dose is evaluated, as well as the secretory antibody response and the development of interferon. Two studies are reported on the transmission from vaccinates to susceptible non-vaccinates and the evaluation of the potential to revert to a more virulent form. An important part is devoted to the latest studies carried out which confirm that wide acceptance should be given to the intranasal vaccination of cattle.", "contents": "Intranasal vaccination of cattle against IBR and PI3: field and laboratory observations in dairy, beef, and neonatal calf populations. The author first summarizes the development of intranasal vaccination by Nasalgen P and particularly Nasalgen IP, previously reported, and then reviews present knowledge regarding safety and efficacy of Nasalgen IP in feeder calves, dairy animals and neonates. The minimal immunogenic dose is evaluated, as well as the secretory antibody response and the development of interferon. Two studies are reported on the transmission from vaccinates to susceptible non-vaccinates and the evaluation of the potential to revert to a more virulent form. An important part is devoted to the latest studies carried out which confirm that wide acceptance should be given to the intranasal vaccination of cattle."} {"id": "PMID:182600", "title": "Transmissible gastroenteritis of swine. Efficacy assay of an intramammary use vaccine.", "content": "TGE seronegative pregnant gilts were vaccinated by intramammary inoculations with a chemically inactivated (betapropiolactone) cell culture virus vaccine and their nursing pigs were exposed to virus at three days of age. The pig morbidity and survival rates were compared with those of pigs nursing gilts exposed orally to virulent TGE virus during late gestation and also with pigs nursing non-vaccinated seronegative sows. The morbidity rates were 100%, 19% and 19%, while the survival rates were 33%, 100% and 17% respectively. The intramammary vaccine used to vaccinate pregnant gilts in this study did not stimulate sufficient antibody response to provide an acceptable level of protection to nursing pigs against experimental challenge with virulent TGE virus. The serum, colostrum and milk TGE neutralizing antibody responses are reported.", "contents": "Transmissible gastroenteritis of swine. Efficacy assay of an intramammary use vaccine. TGE seronegative pregnant gilts were vaccinated by intramammary inoculations with a chemically inactivated (betapropiolactone) cell culture virus vaccine and their nursing pigs were exposed to virus at three days of age. The pig morbidity and survival rates were compared with those of pigs nursing gilts exposed orally to virulent TGE virus during late gestation and also with pigs nursing non-vaccinated seronegative sows. The morbidity rates were 100%, 19% and 19%, while the survival rates were 33%, 100% and 17% respectively. The intramammary vaccine used to vaccinate pregnant gilts in this study did not stimulate sufficient antibody response to provide an acceptable level of protection to nursing pigs against experimental challenge with virulent TGE virus. The serum, colostrum and milk TGE neutralizing antibody responses are reported."} {"id": "PMID:182601", "title": "Comparative studies on parenteral and intranasal inoculation of an attenuated feline herpes virus.", "content": "Using a temperature sensitive mutant of feline herpes virus, comparative studies were carried out regarding efficacy of the intramuscular and the intranasal routes of administration of virus in inducing resistance to feline rhinotracheitis disease. Susceptible adult animals and kittens with and without parental immunity were used. Resistance to disease was measured by serological and challenge methods. Results in terms of rapidity or induced resistance or immunity as well as the degree and duration of immunity are discussed.", "contents": "Comparative studies on parenteral and intranasal inoculation of an attenuated feline herpes virus. Using a temperature sensitive mutant of feline herpes virus, comparative studies were carried out regarding efficacy of the intramuscular and the intranasal routes of administration of virus in inducing resistance to feline rhinotracheitis disease. Susceptible adult animals and kittens with and without parental immunity were used. Resistance to disease was measured by serological and challenge methods. Results in terms of rapidity or induced resistance or immunity as well as the degree and duration of immunity are discussed."} {"id": "PMID:182602", "title": "Effectiveness of orally administered Bordetella pertussis vaccine in mice.", "content": "Oral administration of killed Bordetella pertussis organisms to mice results in increased resistance to an intracerebral infection with virulent B. pertussis cells. The rate of survival is dependent on the dose of antigen. But besides specific systemic immunity, which is persistent over a long period, also transient non-specific resistance is increased. These effects are evidently induced without penetration of bacterial substances into the circulation.", "contents": "Effectiveness of orally administered Bordetella pertussis vaccine in mice. Oral administration of killed Bordetella pertussis organisms to mice results in increased resistance to an intracerebral infection with virulent B. pertussis cells. The rate of survival is dependent on the dose of antigen. But besides specific systemic immunity, which is persistent over a long period, also transient non-specific resistance is increased. These effects are evidently induced without penetration of bacterial substances into the circulation."} {"id": "PMID:182603", "title": "Preliminary results with an oral application of killed Purtussis bacteria in newborn infants.", "content": "Newborn babies have been vaccinated orally on five consecutive days, with 5 droplets of a vaccine containing 10(11) killed Bordetella pertussis. Eight out of twelve subjects showed antibody titres varying between 1:20 and 1:80.", "contents": "Preliminary results with an oral application of killed Purtussis bacteria in newborn infants. Newborn babies have been vaccinated orally on five consecutive days, with 5 droplets of a vaccine containing 10(11) killed Bordetella pertussis. Eight out of twelve subjects showed antibody titres varying between 1:20 and 1:80."} {"id": "PMID:182604", "title": "Effects of early experience on the metabolism and production of corticosterone in rats.", "content": "Rats were handled for 3 min daily for 3 weeks before or after weaning or were left totally undisturbed. At 80 days of age, animals from each group were selected for corticosterone half-life determination. Adrenal tissue from thr remaining animals was incubated in vitro in the presence or absence of ACTH. Handled and unmanipulated animals did nto differ in half-life or in adrenocortical output. These data do not support the hypothesis that the reduced adrenocortical reactivity that results from manipulating animals is due to either the metabolsim of corticosterone or the response of the adrenal cortex to ACTH.", "contents": "Effects of early experience on the metabolism and production of corticosterone in rats. Rats were handled for 3 min daily for 3 weeks before or after weaning or were left totally undisturbed. At 80 days of age, animals from each group were selected for corticosterone half-life determination. Adrenal tissue from thr remaining animals was incubated in vitro in the presence or absence of ACTH. Handled and unmanipulated animals did nto differ in half-life or in adrenocortical output. These data do not support the hypothesis that the reduced adrenocortical reactivity that results from manipulating animals is due to either the metabolsim of corticosterone or the response of the adrenal cortex to ACTH."} {"id": "PMID:182605", "title": "Individual consistency in behavioral states in neonates.", "content": "In this study we identified consistent characteristics of the sleep-wake state of newborn infants. Forty-one normal, full-term infants were observed in a warmer-skin temperature maintained at 36.1 degree C--located in a sound-attenuated room for 1 hr during 2 successive mid-feeding periods. The infant's state was recorded on a check-list every 10 sec using the following categories for sleep and wakefulness: Quiet Sleep A, Quiet Sleep B, Active Sleep Without REM, Active Sleep With REM, Active Sleep With Dense REM, Drowsy, Alert Inactivity, WAKING Activity, Fussing, Crying, and Indefinite State. Immediately following the completion of each observation, the 2 observers made independent judgments of the degree of organization shown by the infant, using a 6-point scale. Over the two 1-hr observations, only Quiet Sleep A, Quiet Sleep B, and Crying showed any consistency. Active Sleep as typically defined showed no consistency whatsoever. However, 2 of the 3 components of Active Sleep were significantly reliability measures for the 2 observations; in sleeping infants all 3 components of active sleep showed high reliability. These results indicate that Active Sleep may be a composite of at least 3 meaningful categories. To look at overall state organization in the neonate, including both sleep and wake states, we considered Active Sleep as 3 separate states and then combined the resulting 11 behavioral states into derived clusters such that each combination of states showed a test-retest reliability above .52. With these 5 state clusters we viewed each infant's state behaviors in terms of a profile depicting the percent of time spent in each state cluster. We found a close association between these profiles and the subjective judgments of sleep-wake state organization made by the observers. The results clearly indicate that a 1-hr observation provides reliable information on individual sleep-wake states in the newborn.", "contents": "Individual consistency in behavioral states in neonates. In this study we identified consistent characteristics of the sleep-wake state of newborn infants. Forty-one normal, full-term infants were observed in a warmer-skin temperature maintained at 36.1 degree C--located in a sound-attenuated room for 1 hr during 2 successive mid-feeding periods. The infant's state was recorded on a check-list every 10 sec using the following categories for sleep and wakefulness: Quiet Sleep A, Quiet Sleep B, Active Sleep Without REM, Active Sleep With REM, Active Sleep With Dense REM, Drowsy, Alert Inactivity, WAKING Activity, Fussing, Crying, and Indefinite State. Immediately following the completion of each observation, the 2 observers made independent judgments of the degree of organization shown by the infant, using a 6-point scale. Over the two 1-hr observations, only Quiet Sleep A, Quiet Sleep B, and Crying showed any consistency. Active Sleep as typically defined showed no consistency whatsoever. However, 2 of the 3 components of Active Sleep were significantly reliability measures for the 2 observations; in sleeping infants all 3 components of active sleep showed high reliability. These results indicate that Active Sleep may be a composite of at least 3 meaningful categories. To look at overall state organization in the neonate, including both sleep and wake states, we considered Active Sleep as 3 separate states and then combined the resulting 11 behavioral states into derived clusters such that each combination of states showed a test-retest reliability above .52. With these 5 state clusters we viewed each infant's state behaviors in terms of a profile depicting the percent of time spent in each state cluster. We found a close association between these profiles and the subjective judgments of sleep-wake state organization made by the observers. The results clearly indicate that a 1-hr observation provides reliable information on individual sleep-wake states in the newborn."} {"id": "PMID:182606", "title": "Standardization fo a digestion-filtration method for isolation of pancreatic islets.", "content": "Standardization of a technic for isolating large numbers of pancreatic islets is described. This procedure employed collagenase digestion of rat pancreatic tissue in a cylindrical wire screen in order to separate isolated islets from undigested pancreas. From this basic protocol the following conditions were established: (1) the duration of the initial digestion period was found to be optimal at six minutes; (2) three subsequent digestions of one minute each effected maximum islet yield; (3) the optimal initial collagenase concentration was found to be 1,000 U. (Worthington)/ml.; and (4) proper reductions of collagenase concentrations during the three subsequent digestions were found to be 50 per cent of each preceding incubation period. This method, combined with Ficoll gradient separation, yielded a mean of 800 islets per two rat pancreases. The isolated islets appeared morphologically intact, contained 0.36 +/- 0.05 mug. protein/islet, and demonstrated a normal biphasic release of insulin in response to stimulative levels of D-glucose. The present method provides a means for obtaining a large mass of viable islet cell tissue in a short time.", "contents": "Standardization fo a digestion-filtration method for isolation of pancreatic islets. Standardization of a technic for isolating large numbers of pancreatic islets is described. This procedure employed collagenase digestion of rat pancreatic tissue in a cylindrical wire screen in order to separate isolated islets from undigested pancreas. From this basic protocol the following conditions were established: (1) the duration of the initial digestion period was found to be optimal at six minutes; (2) three subsequent digestions of one minute each effected maximum islet yield; (3) the optimal initial collagenase concentration was found to be 1,000 U. (Worthington)/ml.; and (4) proper reductions of collagenase concentrations during the three subsequent digestions were found to be 50 per cent of each preceding incubation period. This method, combined with Ficoll gradient separation, yielded a mean of 800 islets per two rat pancreases. The isolated islets appeared morphologically intact, contained 0.36 +/- 0.05 mug. protein/islet, and demonstrated a normal biphasic release of insulin in response to stimulative levels of D-glucose. The present method provides a means for obtaining a large mass of viable islet cell tissue in a short time."} {"id": "PMID:182607", "title": "Incorporation of 75Se-selenomethionine into human apoproteins. III. Kinetic behavior of isotopically labeled plasma apoprotein in man.", "content": "The metabolism of lipoprotein-apoprotein was examined in four subjects with normal lipid metabolism and in one subject with type II hyperlipemia by means of isotopic tracer methodology. Studies were performed after intravenous injection of a radioactive amino acid precursor for apoprotein synthesis (75Se-selenomethionine), in both the basal state and following the acute injection of intravenous heparin. Computer technics were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for serum free amino acid precursor, very-low-density lipoprotein-apoprotein (VLD-apoprotein), and low-density lipoprotein-apoprotein (LDL-apoprotein) in man. The analysis demonstrates that approximately half of the transport of 75Se-apoVLDL from the plasma VLDL pool is converted to 75Se-apoLDL. The acute injection of heparin in two normal subjects results in a two-and-a-half-fold increase in this rate of conversion of 75Se-apoVLDL to 75Se-apoLDL. 75Se-apoLDL is metabolized by rapid transport into a recycling extravascular pool and by irreversible catabolism. The fractional rate of recycling is large relative to the fractional rate of catabolism of apoLDL (3.7:1.0), suggesting extravascular recycling as a potential site of regulation of the plasma concentration of apoLDL. In a patient with type II hyperlipemia, the extravascular recycling pathway is reduced and is not corrected with D-thyroxine therapy. However, this therapy did reduce conversion of apoVLDL to apoLDL in this type II patient. The kinetic data support the validity of the compartmental model in simulating both normal and pathologic apoprotein metabolism and that perturbation of physiology seen with heparin injection and D-thyroxine therapy. These data support a quantitative role of apoVLDL as a precursor of apoLDL and identify an important recycling pathway of apoLDL metabolism in addition to that of catabolism.", "contents": "Incorporation of 75Se-selenomethionine into human apoproteins. III. Kinetic behavior of isotopically labeled plasma apoprotein in man. The metabolism of lipoprotein-apoprotein was examined in four subjects with normal lipid metabolism and in one subject with type II hyperlipemia by means of isotopic tracer methodology. Studies were performed after intravenous injection of a radioactive amino acid precursor for apoprotein synthesis (75Se-selenomethionine), in both the basal state and following the acute injection of intravenous heparin. Computer technics were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for serum free amino acid precursor, very-low-density lipoprotein-apoprotein (VLD-apoprotein), and low-density lipoprotein-apoprotein (LDL-apoprotein) in man. The analysis demonstrates that approximately half of the transport of 75Se-apoVLDL from the plasma VLDL pool is converted to 75Se-apoLDL. The acute injection of heparin in two normal subjects results in a two-and-a-half-fold increase in this rate of conversion of 75Se-apoVLDL to 75Se-apoLDL. 75Se-apoLDL is metabolized by rapid transport into a recycling extravascular pool and by irreversible catabolism. The fractional rate of recycling is large relative to the fractional rate of catabolism of apoLDL (3.7:1.0), suggesting extravascular recycling as a potential site of regulation of the plasma concentration of apoLDL. In a patient with type II hyperlipemia, the extravascular recycling pathway is reduced and is not corrected with D-thyroxine therapy. However, this therapy did reduce conversion of apoVLDL to apoLDL in this type II patient. The kinetic data support the validity of the compartmental model in simulating both normal and pathologic apoprotein metabolism and that perturbation of physiology seen with heparin injection and D-thyroxine therapy. These data support a quantitative role of apoVLDL as a precursor of apoLDL and identify an important recycling pathway of apoLDL metabolism in addition to that of catabolism."} {"id": "PMID:182608", "title": "Stimulatory and inhibitory effects of cyclic AMP on pancreatic glucagon release from monolayer cultures and the controlling role of calcium.", "content": "When glucagon release from monolayer cultures of newborn rat pancreas was measured over four hours in media containing 2.5 mM Ca++, a significant cyclic AMP-related inhibition of release was observed. This was noted whether intracellular cyclic AMP levels were raised by the addition of exogenous cyclic AMP or dibutyryl cyclic AMP, by phosphodiesterase inhibition with theophylline, or by the stimulation of adenylate cyclase with cholera toxin. The inhibition was concentration dependent for cyclic AMP and could not be reproduced by the addition of AMP, ADP or ATP. Adenosine also inhibited glucagon release while ATP was stimulatory. From time course studies it appeared that the inhibitory effects of cyclic AMP and cholera toxin were progressive after two hours of incubation. With cholera toxin an early stimulation of glucagon release was observed. The effects of cyclic AMP and cholera toxin on arginine-stimulated glucagon release were to stimulate further the glucagon release during the first hour of the incubation. Thus, the effects of raising intracellular cyclic AMP levels were biphasic in that both an early stimulation and a late inhibition of glucagon release were observed. In examining the nature of these responses a remarkable controlling role for Ca++ was uncovered: at Ca concentrations of 0.3 mM and lower no effect of cyclic AMP on glucagon release was found. With 1 mM Ca++ in the medium cyclic AMP stimulated glucagon release early (30 min) and thereafter had no further effect. In the presence of 2.5 mM Ca++ cyclic AMP did not stimulate early but did cause the delayed inhibition of release. It is concluded that the effect of cyclic AMP on glucagon release can be either stimulatory or inhibitory depending upon the Ca++ concentration of the medium and the duration of exposure to raised cyclic AMP levels.", "contents": "Stimulatory and inhibitory effects of cyclic AMP on pancreatic glucagon release from monolayer cultures and the controlling role of calcium. When glucagon release from monolayer cultures of newborn rat pancreas was measured over four hours in media containing 2.5 mM Ca++, a significant cyclic AMP-related inhibition of release was observed. This was noted whether intracellular cyclic AMP levels were raised by the addition of exogenous cyclic AMP or dibutyryl cyclic AMP, by phosphodiesterase inhibition with theophylline, or by the stimulation of adenylate cyclase with cholera toxin. The inhibition was concentration dependent for cyclic AMP and could not be reproduced by the addition of AMP, ADP or ATP. Adenosine also inhibited glucagon release while ATP was stimulatory. From time course studies it appeared that the inhibitory effects of cyclic AMP and cholera toxin were progressive after two hours of incubation. With cholera toxin an early stimulation of glucagon release was observed. The effects of cyclic AMP and cholera toxin on arginine-stimulated glucagon release were to stimulate further the glucagon release during the first hour of the incubation. Thus, the effects of raising intracellular cyclic AMP levels were biphasic in that both an early stimulation and a late inhibition of glucagon release were observed. In examining the nature of these responses a remarkable controlling role for Ca++ was uncovered: at Ca concentrations of 0.3 mM and lower no effect of cyclic AMP on glucagon release was found. With 1 mM Ca++ in the medium cyclic AMP stimulated glucagon release early (30 min) and thereafter had no further effect. In the presence of 2.5 mM Ca++ cyclic AMP did not stimulate early but did cause the delayed inhibition of release. It is concluded that the effect of cyclic AMP on glucagon release can be either stimulatory or inhibitory depending upon the Ca++ concentration of the medium and the duration of exposure to raised cyclic AMP levels."} {"id": "PMID:182614", "title": "[In vitro induction of numerical changes in the karyotype of normal and transformed Djungarian and Chinese hamster cells].", "content": "The comparative study of the frequency of colcemid-induced aneuploidy and polyploidy in cultured normal and transformed cells of Djungarian hamster is described. The occurrence of variants with changed chromosome number is much higher in populations of SV40-transformed cell line (4/21) than in normal embryonic cultures. In transformed lines of Djungarian and Chinese hamsters (4/21 and V-79) the frequency of cells with changed chromosome number was found to be dependent on the culture density: the percentage of polyploids was 4-5-fold higher when the number of seeded cells was 2-fold lower. The highest number (18-29%) of hypermodal cells was produced at drug concentrations of 0.02-0.025 mkg/ml. The percengate of polyploids under these conditions reached 10-20. At further increase of colcemid concentrations the proportion of polyploid cells increased. In Djungarian hamster embryonic cell cultures there were single cells with changed chromosome numbers at a concentration of the drug of 0.015-0.1 mkg/ml.", "contents": "[In vitro induction of numerical changes in the karyotype of normal and transformed Djungarian and Chinese hamster cells]. The comparative study of the frequency of colcemid-induced aneuploidy and polyploidy in cultured normal and transformed cells of Djungarian hamster is described. The occurrence of variants with changed chromosome number is much higher in populations of SV40-transformed cell line (4/21) than in normal embryonic cultures. In transformed lines of Djungarian and Chinese hamsters (4/21 and V-79) the frequency of cells with changed chromosome number was found to be dependent on the culture density: the percentage of polyploids was 4-5-fold higher when the number of seeded cells was 2-fold lower. The highest number (18-29%) of hypermodal cells was produced at drug concentrations of 0.02-0.025 mkg/ml. The percengate of polyploids under these conditions reached 10-20. At further increase of colcemid concentrations the proportion of polyploid cells increased. In Djungarian hamster embryonic cell cultures there were single cells with changed chromosome numbers at a concentration of the drug of 0.015-0.1 mkg/ml."} {"id": "PMID:182615", "title": "[Mutagenesis under the influence of simian virus 40 (SV40). II. Induction of mutations for resistance to analogs of purine bases in human and Chinese hamster cells].", "content": "Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cell lines. It is shown that SV40 penetrates into the cells studied and induces the T-antigen synthesis. The efficiency of the infection in Chinese hamster cells was tested additionally by the ability of infected cells to form colonies in the medium lacking serum growth factor. The maximal number of colony-forming cells was detected 24 hours after the infection. By culturing cells in factor-free medium a Chinese hamster cell subline was isolated, which proved to synthetize T-antigen within 60 days after the virus treatment. This is regarded as an indirect proof of the integration of viral genome into the cell genome. The increased frequency of mutants resistant to 60 mkg/ml of 8-azaquanine (human cells) and to 15 or 30 mkg/ml of 6-mercaptopurine (hamster cells) was observed on the 1-4th days following the infection. The analysis of the results of all experiments taken together revealed that the induction is highly significant according to Wilcoxon (greater than 0.99). The resistance of the isolated clones proved to be stable after the prolonged culturing under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosome aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogenesis and tumour progression is discussed.", "contents": "[Mutagenesis under the influence of simian virus 40 (SV40). II. Induction of mutations for resistance to analogs of purine bases in human and Chinese hamster cells]. Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cell lines. It is shown that SV40 penetrates into the cells studied and induces the T-antigen synthesis. The efficiency of the infection in Chinese hamster cells was tested additionally by the ability of infected cells to form colonies in the medium lacking serum growth factor. The maximal number of colony-forming cells was detected 24 hours after the infection. By culturing cells in factor-free medium a Chinese hamster cell subline was isolated, which proved to synthetize T-antigen within 60 days after the virus treatment. This is regarded as an indirect proof of the integration of viral genome into the cell genome. The increased frequency of mutants resistant to 60 mkg/ml of 8-azaquanine (human cells) and to 15 or 30 mkg/ml of 6-mercaptopurine (hamster cells) was observed on the 1-4th days following the infection. The analysis of the results of all experiments taken together revealed that the induction is highly significant according to Wilcoxon (greater than 0.99). The resistance of the isolated clones proved to be stable after the prolonged culturing under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosome aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogenesis and tumour progression is discussed."} {"id": "PMID:182617", "title": "[Genetics and phenogenetics of the hormonal characteristics of animals. II. Changes in the reactivity of the pituitary-adrenal system and influence of the sex glands in selection of silver-black foxes by behavior].", "content": "Seasonal changes in the reactivity of adrenal cortex to ACTH and of the pituitary-adrenal system to psychic stress in intact and castrated domesticated (tame) and non-domesticated (non-tame) silver foxes of both sexes were studied. It is demonstrated that in tame foxes there are differences among the intact and castrated animal in their reaction to ACTH and psychic stress. These differences are maifested especially in autumn (September, October) which is the period of extra-seasonal sexual activity for domesticated animals. This points to the fact that the sex glands exert a great influence on the condition of central regulating mechanisms of the pituitary-adrenal complex and that the selection of silver foxes for tame behaviour changes the functional state of these mechanisms through the change of the functional state of the sex glands.", "contents": "[Genetics and phenogenetics of the hormonal characteristics of animals. II. Changes in the reactivity of the pituitary-adrenal system and influence of the sex glands in selection of silver-black foxes by behavior]. Seasonal changes in the reactivity of adrenal cortex to ACTH and of the pituitary-adrenal system to psychic stress in intact and castrated domesticated (tame) and non-domesticated (non-tame) silver foxes of both sexes were studied. It is demonstrated that in tame foxes there are differences among the intact and castrated animal in their reaction to ACTH and psychic stress. These differences are maifested especially in autumn (September, October) which is the period of extra-seasonal sexual activity for domesticated animals. This points to the fact that the sex glands exert a great influence on the condition of central regulating mechanisms of the pituitary-adrenal complex and that the selection of silver foxes for tame behaviour changes the functional state of these mechanisms through the change of the functional state of the sex glands."} {"id": "PMID:182622", "title": "Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects.", "content": "Bile acid composition was determined in duodenal and jejunal aspirates obtained under fasting conditions in normolipidaemic controls and in patients with the type IIa and type IV lipoprotein patterns. In 17 out of the 22 subjects studied, the duodenal as compared with the jejunal aspirates contained proportionally more CD (chenodeoxycholic acid) than C (cholic acid). The two types of aspirates also differed slightly with regard to the D (deoxycholic acid): CD ratio, which was higher in samples drawn from the jejunum. These findings, compatible with an absorpiton of about 30% of CD in the upper small intestine, were approximately the same in all groups of patients. As evidenced by additional experiments in two subjects, an oral intake of cream does not significantly influence the absorption of CD in the upper small intestine.", "contents": "Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects. Bile acid composition was determined in duodenal and jejunal aspirates obtained under fasting conditions in normolipidaemic controls and in patients with the type IIa and type IV lipoprotein patterns. In 17 out of the 22 subjects studied, the duodenal as compared with the jejunal aspirates contained proportionally more CD (chenodeoxycholic acid) than C (cholic acid). The two types of aspirates also differed slightly with regard to the D (deoxycholic acid): CD ratio, which was higher in samples drawn from the jejunum. These findings, compatible with an absorpiton of about 30% of CD in the upper small intestine, were approximately the same in all groups of patients. As evidenced by additional experiments in two subjects, an oral intake of cream does not significantly influence the absorption of CD in the upper small intestine."} {"id": "PMID:182623", "title": "[Effect of aldosterone and ACTH administration on fluctuation of 5-HT content of the brain and pentobarbital anesthesia in adrenalectomized rats].", "content": "The present study was undertaken to determine whether or not adrenalectomy influences anesthesia and increase in brain 5-HT induced by pentobarbital and if such is the case, whether or not aldosterone or ACTH inhibit the effect of adrenalectomy. Male Wistar rats were adrenalectomized or sham-operated and injected with aldosterone (20mug5hg i.p.), ACTH (5.0 mg/kg i.p.) or the vehicle (1.0 ml/kg i.p.) everyday for 1 week after a postoperative interval of 3 days. These rats ware given a normal diet and 1% saline approximately 5% glucose solution. Animals were injected with pentobatbital (50 mg/kg i.p.) 18 hr after the last injection of each hormone. It was found that adrenalectomy enhanced \"pentobarbital-anesthesia\", although there was no such effect in the adrenalectomized rats pretreated with each hormone. Adrenalectomy inhibited an increase of 5-HT in the brain after pentobarbital, but the hormone pretreatment to those rats did not antagonize the inhibition of the 5-HT increase.", "contents": "[Effect of aldosterone and ACTH administration on fluctuation of 5-HT content of the brain and pentobarbital anesthesia in adrenalectomized rats]. The present study was undertaken to determine whether or not adrenalectomy influences anesthesia and increase in brain 5-HT induced by pentobarbital and if such is the case, whether or not aldosterone or ACTH inhibit the effect of adrenalectomy. Male Wistar rats were adrenalectomized or sham-operated and injected with aldosterone (20mug5hg i.p.), ACTH (5.0 mg/kg i.p.) or the vehicle (1.0 ml/kg i.p.) everyday for 1 week after a postoperative interval of 3 days. These rats ware given a normal diet and 1% saline approximately 5% glucose solution. Animals were injected with pentobatbital (50 mg/kg i.p.) 18 hr after the last injection of each hormone. It was found that adrenalectomy enhanced \"pentobarbital-anesthesia\", although there was no such effect in the adrenalectomized rats pretreated with each hormone. Adrenalectomy inhibited an increase of 5-HT in the brain after pentobarbital, but the hormone pretreatment to those rats did not antagonize the inhibition of the 5-HT increase."} {"id": "PMID:182624", "title": "Clinical application of somatosensory cerebral evoked response for the localization and the level diagnosis of neuronal lesions.", "content": "A new SER recording system using the bilateral simultaneous peripheral nerve stimulation on cervical, thoracic and lumbar segments was found to be helpful as a diagnostic aid for the localization and the level diagnosis of sensory neuronal lesions including peripheral nerves. SER abnormalities were observed in 32 (76.2%) of the 42 cases with cerebrovascular disease, in 11 (64.7%) of the 17 cases with spinal cord lesions and 12 (75.0%) of the 16 cases with peripheral nerve lesions. As an interesting finding, marked SER abnormalities corresponding with the level and the distribution of the lesions were observed in cases with spinal cord tumor, myelopathy and polyneuropathy. In a case with recurrent myelitis, lesions of different levels of spinal cord were suggested from the SER changes. The recording system gives also valuable information about chronological modifications of the lesions, and may reveal subclinical neuronal damage in a certain neurological disorder.", "contents": "Clinical application of somatosensory cerebral evoked response for the localization and the level diagnosis of neuronal lesions. A new SER recording system using the bilateral simultaneous peripheral nerve stimulation on cervical, thoracic and lumbar segments was found to be helpful as a diagnostic aid for the localization and the level diagnosis of sensory neuronal lesions including peripheral nerves. SER abnormalities were observed in 32 (76.2%) of the 42 cases with cerebrovascular disease, in 11 (64.7%) of the 17 cases with spinal cord lesions and 12 (75.0%) of the 16 cases with peripheral nerve lesions. As an interesting finding, marked SER abnormalities corresponding with the level and the distribution of the lesions were observed in cases with spinal cord tumor, myelopathy and polyneuropathy. In a case with recurrent myelitis, lesions of different levels of spinal cord were suggested from the SER changes. The recording system gives also valuable information about chronological modifications of the lesions, and may reveal subclinical neuronal damage in a certain neurological disorder."} {"id": "PMID:182625", "title": "An anatomicopathological approach to the study of articular aging.", "content": "Bone and joint aging results from the combined action of various metabolic and mechanical factors. Osteoarticular aging produces primary changes in bone (intrinsic rarefaction, but also extrinsic osteogenesis), cartilage, synovial membrane, and tendon. The association of these primary changes can result basically in three anatomicopathological entities: hyperostosis and osteophytes at tendon insertions, senile remodeling, and osteoarthritic remodeling. Some of these entities are asymptomatic. Others form part of nosologic entities such as osteoarthritis and various types of joint pain and stiffness. The standard methods of morbid anatomy provide a link between clinical findings and modern research methods. By separating nosology and morphology they permit a better analysis of the boundaries and transitions between articular \"aging\" and \"disease\". With advancing age, osteoarthritis becomes increasingly frequent but not inevitable.", "contents": "An anatomicopathological approach to the study of articular aging. Bone and joint aging results from the combined action of various metabolic and mechanical factors. Osteoarticular aging produces primary changes in bone (intrinsic rarefaction, but also extrinsic osteogenesis), cartilage, synovial membrane, and tendon. The association of these primary changes can result basically in three anatomicopathological entities: hyperostosis and osteophytes at tendon insertions, senile remodeling, and osteoarthritic remodeling. Some of these entities are asymptomatic. Others form part of nosologic entities such as osteoarthritis and various types of joint pain and stiffness. The standard methods of morbid anatomy provide a link between clinical findings and modern research methods. By separating nosology and morphology they permit a better analysis of the boundaries and transitions between articular \"aging\" and \"disease\". With advancing age, osteoarthritis becomes increasingly frequent but not inevitable."} {"id": "PMID:182626", "title": "[Diagnosis of breast carcinoma. Value of x-ray findings for the diagnosis of carcinoma in situ of the breast from the clinical point of view].", "content": "The x-rays-results of 35 mammae with a carcinoma in situ are presented and compared with those of 2 groups without carcinoma. In contradiction to invasive malignancies the carcinoma in situ do not show pathognomonic signs on x-ray examination. However, suspicion is raised by the appearance of microcalcifications and by striped differences in tissue density. These findings should compell to perform a biopsy, even though the clinical and roentgenologic findings may otherwise suggest a fibrocystic disease. Therefore, provided the discrete signs described in this paper are carefully considered, the technique of mammography may contribute to the pre-operative presumptive diagnosis of carcinoma in situ.", "contents": "[Diagnosis of breast carcinoma. Value of x-ray findings for the diagnosis of carcinoma in situ of the breast from the clinical point of view]. The x-rays-results of 35 mammae with a carcinoma in situ are presented and compared with those of 2 groups without carcinoma. In contradiction to invasive malignancies the carcinoma in situ do not show pathognomonic signs on x-ray examination. However, suspicion is raised by the appearance of microcalcifications and by striped differences in tissue density. These findings should compell to perform a biopsy, even though the clinical and roentgenologic findings may otherwise suggest a fibrocystic disease. Therefore, provided the discrete signs described in this paper are carefully considered, the technique of mammography may contribute to the pre-operative presumptive diagnosis of carcinoma in situ."} {"id": "PMID:182627", "title": "[Directed chemotherapy of neoplastic diseases. Significance of the purine-de novo synthesis and cyclic AMP in normal and leukemic leukocytes].", "content": "Studies on purine de novo-synthesis and cyclic AMP in normal and pathologic leukocytes. The destruction of neoplastic cells by cytostatic agents depends on the existence of metabolic reactions within the cells which can be specifically blocked by these agents. Concerning the action of purine antagonists there is, as yet, no clear evidence whether de novo synthesis of purines takes place in normal as well as in leukemic leukocytes. Therefore studies were performed to evaluate the capacity of these cells to incorporate the purine precursor, glycine, into their acid-soluble adenine nucleotides. The results demonstrate that \"resting\" human lymphocytes are not capable of building purines de novo. However, stimulation of the cells with a mitogen (Phytohemagglutinin) leads to the induction of de novo purine synthesis. Leukemic cells do not show uniform behaviour. In order to get more information about the mechanisms by which synthesis of purines as well as the morphologic transformation of lymphocytes may be induced, the metabolism of cyclic AMP was investigated. According to our results the nucleotide does not play an essential role in initiating the transformation process, but it seems to have regulating function in the further development of cell transformation. The studies furthermore indicate an important role of cyclic AMP during proliferation of leukemic cells.", "contents": "[Directed chemotherapy of neoplastic diseases. Significance of the purine-de novo synthesis and cyclic AMP in normal and leukemic leukocytes]. Studies on purine de novo-synthesis and cyclic AMP in normal and pathologic leukocytes. The destruction of neoplastic cells by cytostatic agents depends on the existence of metabolic reactions within the cells which can be specifically blocked by these agents. Concerning the action of purine antagonists there is, as yet, no clear evidence whether de novo synthesis of purines takes place in normal as well as in leukemic leukocytes. Therefore studies were performed to evaluate the capacity of these cells to incorporate the purine precursor, glycine, into their acid-soluble adenine nucleotides. The results demonstrate that \"resting\" human lymphocytes are not capable of building purines de novo. However, stimulation of the cells with a mitogen (Phytohemagglutinin) leads to the induction of de novo purine synthesis. Leukemic cells do not show uniform behaviour. In order to get more information about the mechanisms by which synthesis of purines as well as the morphologic transformation of lymphocytes may be induced, the metabolism of cyclic AMP was investigated. According to our results the nucleotide does not play an essential role in initiating the transformation process, but it seems to have regulating function in the further development of cell transformation. The studies furthermore indicate an important role of cyclic AMP during proliferation of leukemic cells."} {"id": "PMID:182629", "title": "Interactions of glucagon and related peptides with chicken adipose tissue.", "content": "The effect of glucagon, Vasoactive Intestinal Polypeptide (VIP), secretin and gut glucagon on the cyclic adenosine 3'5' monophosphate (cAMP) level, and on the specific binding of these 125I-peptides to the adipocyte plasma membrane was measured in chicken adipocytes and compared to the results obtained in rat adipocytes. The displacement of 125I-glucagon from its specific sites was observed with about the same concentration of unlabeled hormone in fat cell plasma membranes of both species. However, the rise in cAMP induced by glucagon was much higher in chicken than in rat adipocytes. In chicken fat cells unlike rat fat cells, the cAMP accumulation elicited by glucagon was maintained during at least 60 min even in the absence of theophylline. Theophylline at 1-10 mM potentiated the glucagon-stimulated cAMP levels in rat fat cells, but had only a slight effect, if any, in chicken adiposyces. Porcine VIP, secretin or gut glucagon exerted no detectable action on the cAMP level of chicken adipocytes. The lack of cAMP accumulation was in good agreement with the absence of binding of 125I-VIP and 125I-secretin by chicken plasma membranes. These findings suggest that: 1) the difference of glucagon effect in rat and chicken fat cells results from variations in the rate of degradation of cAMP rather than from differences in the specific binding of glucagon between the two species; 2) the use of chicken fat cells is suitable to discriminate between glucagon and structurally related peptides from mammals.", "contents": "Interactions of glucagon and related peptides with chicken adipose tissue. The effect of glucagon, Vasoactive Intestinal Polypeptide (VIP), secretin and gut glucagon on the cyclic adenosine 3'5' monophosphate (cAMP) level, and on the specific binding of these 125I-peptides to the adipocyte plasma membrane was measured in chicken adipocytes and compared to the results obtained in rat adipocytes. The displacement of 125I-glucagon from its specific sites was observed with about the same concentration of unlabeled hormone in fat cell plasma membranes of both species. However, the rise in cAMP induced by glucagon was much higher in chicken than in rat adipocytes. In chicken fat cells unlike rat fat cells, the cAMP accumulation elicited by glucagon was maintained during at least 60 min even in the absence of theophylline. Theophylline at 1-10 mM potentiated the glucagon-stimulated cAMP levels in rat fat cells, but had only a slight effect, if any, in chicken adiposyces. Porcine VIP, secretin or gut glucagon exerted no detectable action on the cAMP level of chicken adipocytes. The lack of cAMP accumulation was in good agreement with the absence of binding of 125I-VIP and 125I-secretin by chicken plasma membranes. These findings suggest that: 1) the difference of glucagon effect in rat and chicken fat cells results from variations in the rate of degradation of cAMP rather than from differences in the specific binding of glucagon between the two species; 2) the use of chicken fat cells is suitable to discriminate between glucagon and structurally related peptides from mammals."} {"id": "PMID:182630", "title": "Influence of the assay conditions on the lipolytic potency in vitro of different adrenocorticotrophins.", "content": "The lipolytic activity of ACTH-(1-39) and ACTH-(1-24) in vitro has been compared on a molar basis in assays performed with both adipose-tissue slices and isolated fat cells. In the tissue-slice assay ACTH-(1-24) displayed 29% of the potency of ACTH-(1-39), whereas in the isolated-cell assay, ACTH-(1-24) was 3.9 times more potent than the longer peptide. This discrepancy seems to be due to the fact that ACTH-peptides are inactivated in the adipose-tissue-slice assay, but remain stable in the isolated-fat-cell assay. ACTH-(1-24) is inactivated more rapidly than ACTH-(1-39). Pre-incubation and washing of the tissue slices removes the inactivating principle, which most likely consists of peptidases, and their responsiveness is increased, so that both ACTH-peptides display similar lipolytic activity to that seen in the isolated-cell system. Comparison of the responsiveness of isolated fat cells and isolated adrenal cells indicates that the affinity of ACTH for the receptor of adrenal cells is approximately 100 times greater than its affinity for the fat-cell receptor.", "contents": "Influence of the assay conditions on the lipolytic potency in vitro of different adrenocorticotrophins. The lipolytic activity of ACTH-(1-39) and ACTH-(1-24) in vitro has been compared on a molar basis in assays performed with both adipose-tissue slices and isolated fat cells. In the tissue-slice assay ACTH-(1-24) displayed 29% of the potency of ACTH-(1-39), whereas in the isolated-cell assay, ACTH-(1-24) was 3.9 times more potent than the longer peptide. This discrepancy seems to be due to the fact that ACTH-peptides are inactivated in the adipose-tissue-slice assay, but remain stable in the isolated-fat-cell assay. ACTH-(1-24) is inactivated more rapidly than ACTH-(1-39). Pre-incubation and washing of the tissue slices removes the inactivating principle, which most likely consists of peptidases, and their responsiveness is increased, so that both ACTH-peptides display similar lipolytic activity to that seen in the isolated-cell system. Comparison of the responsiveness of isolated fat cells and isolated adrenal cells indicates that the affinity of ACTH for the receptor of adrenal cells is approximately 100 times greater than its affinity for the fat-cell receptor."} {"id": "PMID:182631", "title": "Isolated corticotrophin-deficiency found through alcohol-induced hypoglycemic coma.", "content": "A case of hypoglycemic coma after alcohol ingestion was observed in a chronic alcoholic. Upon close examination isolated corticotrophin-deficiency was found. It is suggested that ethanol-induced hypoglycemia may be consistent with dysfunction of mitochondria in hepatic cells and that there may be disorder of the hypothalamus in the chronic drinker.", "contents": "Isolated corticotrophin-deficiency found through alcohol-induced hypoglycemic coma. A case of hypoglycemic coma after alcohol ingestion was observed in a chronic alcoholic. Upon close examination isolated corticotrophin-deficiency was found. It is suggested that ethanol-induced hypoglycemia may be consistent with dysfunction of mitochondria in hepatic cells and that there may be disorder of the hypothalamus in the chronic drinker."} {"id": "PMID:182632", "title": "Urinary cyclic 3',5'-adenosine monophosphate (cAMP) in diabetic subjects with and without symptomatic hypoglycemia and in normal subjects with insulin-induced hypoglycemia.", "content": "Urinary cAMP was investigated in diabetic subjects. It was found normal in patients on oral antidiabetics and on insulin in good or poor control. Patients with insulin-induced symptomatic hypoglycemia, however, excreted increased amounts of cAMP in the urine. To demonstrate the significance of hypoglycemia we induced hypoglycemia by i.v.-injection of 0.15 U insulin/kg body weight in six normal subjects. An increase of urinary cAMP was found even during the first 15 minutes with maximal hypoglycemia. Determination of urinary cAMP seems to be helpful in the diagnosis of unrecognized hypoglycemia and counterregulation.", "contents": "Urinary cyclic 3',5'-adenosine monophosphate (cAMP) in diabetic subjects with and without symptomatic hypoglycemia and in normal subjects with insulin-induced hypoglycemia. Urinary cAMP was investigated in diabetic subjects. It was found normal in patients on oral antidiabetics and on insulin in good or poor control. Patients with insulin-induced symptomatic hypoglycemia, however, excreted increased amounts of cAMP in the urine. To demonstrate the significance of hypoglycemia we induced hypoglycemia by i.v.-injection of 0.15 U insulin/kg body weight in six normal subjects. An increase of urinary cAMP was found even during the first 15 minutes with maximal hypoglycemia. Determination of urinary cAMP seems to be helpful in the diagnosis of unrecognized hypoglycemia and counterregulation."} {"id": "PMID:182633", "title": "Long-term treatment of acromegaly with bromocryptine: postprandial HGH levels and response to TRH and glucose administration.", "content": "Fourteen patients with acromegaly were treated with bromocryptine (CB 154, Sandoz), 4 X 2.5 mg, for periods of up to eleven months. One patient did not tolerate the drug, ten of the remaining thirteen experienced considerable clinical improvement. There was a dose-dependent suppression of plasma growth hormone levels, but growth hormone response to TRH injection and to glucose administration was still present during therapy although reduced. TSH response to TRH was not significantly altered. The suppressive power of bromocryptine on growth hormone appears to be related to the mechanism by which TRH stimulates growth hormone secretion in acromegaly, but long-term administration of this drug may be successful in spite of an absent response to TRH in some cases. Bromocryptine appears to be a safe and effective drug for the treatment of acromegaly.", "contents": "Long-term treatment of acromegaly with bromocryptine: postprandial HGH levels and response to TRH and glucose administration. Fourteen patients with acromegaly were treated with bromocryptine (CB 154, Sandoz), 4 X 2.5 mg, for periods of up to eleven months. One patient did not tolerate the drug, ten of the remaining thirteen experienced considerable clinical improvement. There was a dose-dependent suppression of plasma growth hormone levels, but growth hormone response to TRH injection and to glucose administration was still present during therapy although reduced. TSH response to TRH was not significantly altered. The suppressive power of bromocryptine on growth hormone appears to be related to the mechanism by which TRH stimulates growth hormone secretion in acromegaly, but long-term administration of this drug may be successful in spite of an absent response to TRH in some cases. Bromocryptine appears to be a safe and effective drug for the treatment of acromegaly."} {"id": "PMID:182634", "title": "Effect of an oral contraceptive on the lysine-8-vasopressin test in the diagnostic evaluation of pituitary function.", "content": "A comparative study was performed on the plasma 11-hydroxycorticosteroids (11-OHCS) responses to lysine-8-vasopressin (LVP) before and during ingestion of an oral contraceptive wieh oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma 11-OHCS content in blood samples at 8 a.m. and 4 p.m. were included in the study. The results show that the mean response of plasma 11-OHCS to the administration of LVP was equal in magnitude before and during ingestion of the contraceptive, although the baseline value of 11-OHCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase of plasma 11-OHCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma 11-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The inidvidual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed.", "contents": "Effect of an oral contraceptive on the lysine-8-vasopressin test in the diagnostic evaluation of pituitary function. A comparative study was performed on the plasma 11-hydroxycorticosteroids (11-OHCS) responses to lysine-8-vasopressin (LVP) before and during ingestion of an oral contraceptive wieh oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma 11-OHCS content in blood samples at 8 a.m. and 4 p.m. were included in the study. The results show that the mean response of plasma 11-OHCS to the administration of LVP was equal in magnitude before and during ingestion of the contraceptive, although the baseline value of 11-OHCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase of plasma 11-OHCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma 11-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The inidvidual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed."} {"id": "PMID:182635", "title": "Studies in vivo on the effects of parathyroid hormone upon kidney cyclic adenosine 3',5'-monophosphate content using rapid tissue fixation by microwave irradiation.", "content": "Microwave irradiation is shown to be a useful method for simultaneously killing chicks and fixing tissues. Renal adenylate cyclase and phosphodiesterase activities were rapidly abolished by microwaving. The increase in chick kidney cyclic adenosine 3',5'-monophosphate (cyclic AMP) content produced by intravenous bovine parathyroid hormone (PTH) injection was much greater in microwaved birds than in those killed by cervical dislocation with subsequent tissue fixation in liquid nitrogen. After PTH injection there was a prolonged elevation of renal cyclic AMP content. At the time of maximum response (2 minutes), log. dose-response curves were linear in the dose range 0.1-10 U. The responses to three different bovine PTH preparations were indistinguishable. Arginine vasopressin, arginine vasotocin, salmon calcitonin and prostaglandin E1 did not affect kidney cyclic AMP content within 2 minutes. Because of its specificity and precision, the method is of use for the in vivo bioassay of PTH. Injection of CaCl2 (20 mumoles) 1 minute before, or conjointly with, bovine PTH inhibited the subsequent increase in kidney cyclic AMP content. The synthetic bovine PTH peptide fragments BPTH (1-34) and BPTH (2-34) both increased chick kidney cyclic AMP content. The use of such fragments allows investigation of the structural requirements of PTH for interaction with the systems regulating cyclic AMP metabolism in the kidney in vivo.", "contents": "Studies in vivo on the effects of parathyroid hormone upon kidney cyclic adenosine 3',5'-monophosphate content using rapid tissue fixation by microwave irradiation. Microwave irradiation is shown to be a useful method for simultaneously killing chicks and fixing tissues. Renal adenylate cyclase and phosphodiesterase activities were rapidly abolished by microwaving. The increase in chick kidney cyclic adenosine 3',5'-monophosphate (cyclic AMP) content produced by intravenous bovine parathyroid hormone (PTH) injection was much greater in microwaved birds than in those killed by cervical dislocation with subsequent tissue fixation in liquid nitrogen. After PTH injection there was a prolonged elevation of renal cyclic AMP content. At the time of maximum response (2 minutes), log. dose-response curves were linear in the dose range 0.1-10 U. The responses to three different bovine PTH preparations were indistinguishable. Arginine vasopressin, arginine vasotocin, salmon calcitonin and prostaglandin E1 did not affect kidney cyclic AMP content within 2 minutes. Because of its specificity and precision, the method is of use for the in vivo bioassay of PTH. Injection of CaCl2 (20 mumoles) 1 minute before, or conjointly with, bovine PTH inhibited the subsequent increase in kidney cyclic AMP content. The synthetic bovine PTH peptide fragments BPTH (1-34) and BPTH (2-34) both increased chick kidney cyclic AMP content. The use of such fragments allows investigation of the structural requirements of PTH for interaction with the systems regulating cyclic AMP metabolism in the kidney in vivo."} {"id": "PMID:182637", "title": "Purification and characterization of N-acetylneuraminate lyase from Clostridium perfringens.", "content": "Clostridium perfringens cells were cultivated on a large scale using an automatic system. 2) N-Acetylneuraminate lyase, which is a cytosolic enzyme, was liberated from the bacteria by cell lysis using lysozyme in hypotonic solution. The enzyme was purified 770-fold by precepitation with ammonium sulfate, filtration on Sephadex A-50 and final preparative electrophoresis in a 7.5% polyacrylamide gel. Yield: 12 mg from 1 kg wet cell paste; specific activity: 167 nkat/mg protein. 3) The enzyme preparation appeared homogeneous in analytical disc electrophoresis, in gel electrophroesis in 0.1% sodium dodecylsulfate or 8m urea and in immunoelectrophoresis. Contaminating enzyme activities were not detected. 4) The isoelectric point of pH 4.7 was found for the enzyme. At 278 nm a molar extinction coefficient of 6.4 x 10(4)M-1 Xcm-1 was determined. The enzyme exhibited a Km value for N-acetylneuraminic acid of 2.8mM at its pH optimum of pH 7.2. The pH dependence of the Km value gives evidence that an ionizing guoup in the active center of the enzyme with a pKe value of 6.4 may be involved in the catalytic reaction. Pyruvate inhibited the cleavage reaction of N-acetylneuraminic acid competitively; Ki = 2.9mM. 5) An average molecular weight of 99200 was determined for the native enzyme using different methods. After denaturation in sokium dodecylsulfate or urea, a mean molecular weight of only 50000 could be demonstrated, indicating the existence of two enzyme subunits. The lyase molecule was shown by electron microscopy, using a negative staining technique, to consist of two hemispherical parts. 6) Two active sites per native enzyme molecule, probably corresponding to one active site per subunit, were found by incubation of the enzyme with radioactive pyruvate followed by borohydride reduction. The results obtained from chemical modification of the lyase with 5-diazonium-1H-tetrazole and iodocaetamide under various conditionsare interpreted as evidence for the presence of two reactive histidine residues in the enzyme molecule. It is probable that one residue per subunit forms the nucleophilic group participating in enzyme catalysis. A model suggesting the mechanism of reversible cleavage of N-acylneuraminic acids by the lyase is presented.", "contents": "Purification and characterization of N-acetylneuraminate lyase from Clostridium perfringens. Clostridium perfringens cells were cultivated on a large scale using an automatic system. 2) N-Acetylneuraminate lyase, which is a cytosolic enzyme, was liberated from the bacteria by cell lysis using lysozyme in hypotonic solution. The enzyme was purified 770-fold by precepitation with ammonium sulfate, filtration on Sephadex A-50 and final preparative electrophoresis in a 7.5% polyacrylamide gel. Yield: 12 mg from 1 kg wet cell paste; specific activity: 167 nkat/mg protein. 3) The enzyme preparation appeared homogeneous in analytical disc electrophoresis, in gel electrophroesis in 0.1% sodium dodecylsulfate or 8m urea and in immunoelectrophoresis. Contaminating enzyme activities were not detected. 4) The isoelectric point of pH 4.7 was found for the enzyme. At 278 nm a molar extinction coefficient of 6.4 x 10(4)M-1 Xcm-1 was determined. The enzyme exhibited a Km value for N-acetylneuraminic acid of 2.8mM at its pH optimum of pH 7.2. The pH dependence of the Km value gives evidence that an ionizing guoup in the active center of the enzyme with a pKe value of 6.4 may be involved in the catalytic reaction. Pyruvate inhibited the cleavage reaction of N-acetylneuraminic acid competitively; Ki = 2.9mM. 5) An average molecular weight of 99200 was determined for the native enzyme using different methods. After denaturation in sokium dodecylsulfate or urea, a mean molecular weight of only 50000 could be demonstrated, indicating the existence of two enzyme subunits. The lyase molecule was shown by electron microscopy, using a negative staining technique, to consist of two hemispherical parts. 6) Two active sites per native enzyme molecule, probably corresponding to one active site per subunit, were found by incubation of the enzyme with radioactive pyruvate followed by borohydride reduction. The results obtained from chemical modification of the lyase with 5-diazonium-1H-tetrazole and iodocaetamide under various conditionsare interpreted as evidence for the presence of two reactive histidine residues in the enzyme molecule. It is probable that one residue per subunit forms the nucleophilic group participating in enzyme catalysis. A model suggesting the mechanism of reversible cleavage of N-acylneuraminic acids by the lyase is presented."} {"id": "PMID:182638", "title": "[Coenzym properties of some Ade-1- and Ade-N6-substituted NAD derivatives (author's transl)].", "content": "By reaction of NAD with different oxiranes or with aziridine, derivatives of the coenzyme are obtained with substituents in position 1 or on the amino group in position 6 of the adenine ring. While the Ade-1-substituted derivatives show high Km values with different dehydrogenases and are reduced only very slowly by these enzymes, the coenzyme derivatives substituted at the amino group behave very similarly to NAD. Correlations were found between coenzyme efficiency of the compounds and the lipophilic character of their substituents. The results can be interpreted from the structure of the active site of the dehydrogenases investigated.", "contents": "[Coenzym properties of some Ade-1- and Ade-N6-substituted NAD derivatives (author's transl)]. By reaction of NAD with different oxiranes or with aziridine, derivatives of the coenzyme are obtained with substituents in position 1 or on the amino group in position 6 of the adenine ring. While the Ade-1-substituted derivatives show high Km values with different dehydrogenases and are reduced only very slowly by these enzymes, the coenzyme derivatives substituted at the amino group behave very similarly to NAD. Correlations were found between coenzyme efficiency of the compounds and the lipophilic character of their substituents. The results can be interpreted from the structure of the active site of the dehydrogenases investigated."} {"id": "PMID:182639", "title": "Placental enzyme polymorphisms in Canadian populations.", "content": "Phenotype distributions and allele frequencies of adenylate kinase and esterase D were determined for four Canadian populations. In two population samples from south-western Ontario, allele frequencies at both loci were similar to those of European populations. In two northern, indigenous populations, the allele AK2 was not detected. There was variation at the EsD locus with EsD2 having a frequency of 0.176 in an Indian population, and 0.156 in an Eskimo population.", "contents": "Placental enzyme polymorphisms in Canadian populations. Phenotype distributions and allele frequencies of adenylate kinase and esterase D were determined for four Canadian populations. In two population samples from south-western Ontario, allele frequencies at both loci were similar to those of European populations. In two northern, indigenous populations, the allele AK2 was not detected. There was variation at the EsD locus with EsD2 having a frequency of 0.176 in an Indian population, and 0.156 in an Eskimo population."} {"id": "PMID:182642", "title": "A sensitive and reproducible assay for the quantitation of erythrophagocytosis and its correlation with reduction in tritiated thymidine uptake in a tumor target cell system modified by immunoenhancing or immunosuppressive agents.", "content": "A new and sensitive assay procedure for studying erythrophagocytosis is described. The assay technique permits quantitation of the in vivo and in vitro effects of chemicals, hormones, and cell, or microbrial products, on the level of phagocytic activation of glass-adherent cells. The effect of intraperitoneal injection of BCG, Zymosan, Vitamin A, B. pertussis, cortisone, estrone, and thioglycollate on phagocytic activation of peritoneal exudate cells harvested from two days up to 28 days following drug injection was examined by this assay. Erythrophagocytosis was compared to the effect of \"activated\" spleen cells on tritiated thymidine uptake of a tumor target cell suspension.", "contents": "A sensitive and reproducible assay for the quantitation of erythrophagocytosis and its correlation with reduction in tritiated thymidine uptake in a tumor target cell system modified by immunoenhancing or immunosuppressive agents. A new and sensitive assay procedure for studying erythrophagocytosis is described. The assay technique permits quantitation of the in vivo and in vitro effects of chemicals, hormones, and cell, or microbrial products, on the level of phagocytic activation of glass-adherent cells. The effect of intraperitoneal injection of BCG, Zymosan, Vitamin A, B. pertussis, cortisone, estrone, and thioglycollate on phagocytic activation of peritoneal exudate cells harvested from two days up to 28 days following drug injection was examined by this assay. Erythrophagocytosis was compared to the effect of \"activated\" spleen cells on tritiated thymidine uptake of a tumor target cell suspension."} {"id": "PMID:182643", "title": "Genetic role of rat macrophage cytotoxicity against tumor.", "content": "Macrophages from the Lewis (Le) rat strain are significantly more cytotoxic to a Moloney sarcoma tumor both in vivo and in vitro, than are macrophages from the Brown Norway (BN) strain. Activity of macrophages from (Le x BN)F1 rats that are histocompatible with the Moloney sarcoma tumor is directed toward tumor and/or virus-associated antigens and is expressed as a dominant genetic trait. Experiments with backcross rats suggest that the genetic factors are unrelated to the major histocompatibility locus (AgB) of the rats. BN microphages, although not active against tumor and/or viral antigens, can become cytotoxic to cells displaying Le alloantigens.", "contents": "Genetic role of rat macrophage cytotoxicity against tumor. Macrophages from the Lewis (Le) rat strain are significantly more cytotoxic to a Moloney sarcoma tumor both in vivo and in vitro, than are macrophages from the Brown Norway (BN) strain. Activity of macrophages from (Le x BN)F1 rats that are histocompatible with the Moloney sarcoma tumor is directed toward tumor and/or virus-associated antigens and is expressed as a dominant genetic trait. Experiments with backcross rats suggest that the genetic factors are unrelated to the major histocompatibility locus (AgB) of the rats. BN microphages, although not active against tumor and/or viral antigens, can become cytotoxic to cells displaying Le alloantigens."} {"id": "PMID:182644", "title": "Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. I. Virus replication in lymphocytes infected with Friend virus and cultures in diffusion chambers in vivo.", "content": "A new technique for infection of mature lymphocytes with murine leukemia virus (Friend) MuLV-F) is described. Spleen cells for normal, non-infected donors were placed into diffusion chambers (constructed with 0.22 mum por size Millipore filters) which were then implanted into the peritoneal cavities of normal syngeneic recipient mice. The cells were infected with an injection of MuLV-F into the peritoneal cavity and, in some instances, also by placing virus into the chambers. Cells were recovered by treating the chamber content with elastase and collagenase. The infection was determined in two ways: (1) cells with replicating MuLV were enumerated as infection centers (IC) on S+L- indicator cells; and (2) virus-related cell membrane antigen (MA) was detected by immunofluorescence. Cells recovered from chambers after 2-3 weeks of culture represented about 10% of the original inoculum; viability was approximately 90%. The number of IC in MuLV-F-infected chambers was about 10 times higher than obtained by infection and cultivation of spleen cells in vitro. The kinetics of IC and MA in chamber-cultured. MuLV-F-infected spleen cells was similar to that in the spleen of infected mice during the first 10 days after infection. Later on, the process of infection within the chambers slowed down, reaching about 50% MA-positive and about 10% IC-positive cells, whereas the number of both IC- and MA-positive cells in the spleen reached 80% or more. The infection of splenic lymphocytes in diffusion chambers occurred equally well when chambers were implanted into: (1) syngeneic, virus susceptible hosts; (2) syngeneic, lethally irradiated hosts; and (3) allogeneic, virus-resistant hosts, suggesting that the process within the chamber is independent of MuLV replication in the tissues of the chamber-bearing mouse. The diffusion chamber technique seems to provide an environment in which various types of isolated lymphocytes of different mouse strains can interact with MuLV almost as efficiently as in vivo.", "contents": "Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. I. Virus replication in lymphocytes infected with Friend virus and cultures in diffusion chambers in vivo. A new technique for infection of mature lymphocytes with murine leukemia virus (Friend) MuLV-F) is described. Spleen cells for normal, non-infected donors were placed into diffusion chambers (constructed with 0.22 mum por size Millipore filters) which were then implanted into the peritoneal cavities of normal syngeneic recipient mice. The cells were infected with an injection of MuLV-F into the peritoneal cavity and, in some instances, also by placing virus into the chambers. Cells were recovered by treating the chamber content with elastase and collagenase. The infection was determined in two ways: (1) cells with replicating MuLV were enumerated as infection centers (IC) on S+L- indicator cells; and (2) virus-related cell membrane antigen (MA) was detected by immunofluorescence. Cells recovered from chambers after 2-3 weeks of culture represented about 10% of the original inoculum; viability was approximately 90%. The number of IC in MuLV-F-infected chambers was about 10 times higher than obtained by infection and cultivation of spleen cells in vitro. The kinetics of IC and MA in chamber-cultured. MuLV-F-infected spleen cells was similar to that in the spleen of infected mice during the first 10 days after infection. Later on, the process of infection within the chambers slowed down, reaching about 50% MA-positive and about 10% IC-positive cells, whereas the number of both IC- and MA-positive cells in the spleen reached 80% or more. The infection of splenic lymphocytes in diffusion chambers occurred equally well when chambers were implanted into: (1) syngeneic, virus susceptible hosts; (2) syngeneic, lethally irradiated hosts; and (3) allogeneic, virus-resistant hosts, suggesting that the process within the chamber is independent of MuLV replication in the tissues of the chamber-bearing mouse. The diffusion chamber technique seems to provide an environment in which various types of isolated lymphocytes of different mouse strains can interact with MuLV almost as efficiently as in vivo."} {"id": "PMID:182645", "title": "Detection of anti-tumor antibody in virally induced tumors and its relationship to tumor growth.", "content": "The humoral antibody response to virally induced tumors insyngeneic hosts has been studied. The tumors include an SV40 tumor SVT2, the Friend virus-induced leukemias FBL-3 and FLC; and Moloney sarcoma virus-induced tumors. It was found that antitumor antibodies could be detected by the isotopic antiglobulin technique in these tumor systems at a relatively early stage of tumor growth. The kinetics of the antibody response in relation to the status of tumor growth varied between different tumors. In geneumor growth than in the regressors of tumor-free hosts. Reinoculation of tumor cells or recurrence of tumor growth produced elevation of antibody levels (secondary response). The specificity of the antibody reactions also varied in different tumor systems: some antibodies were truly tumor-specific and thus might produce a biological effect on in vivo tumor immunity, whereas others were not. These studies indicated that a sensitive antibody assay could be used for early detection of tumor growth. However, its usefulness in evaluation of the status of tumor growth should be carefully studied in each tumor system.", "contents": "Detection of anti-tumor antibody in virally induced tumors and its relationship to tumor growth. The humoral antibody response to virally induced tumors insyngeneic hosts has been studied. The tumors include an SV40 tumor SVT2, the Friend virus-induced leukemias FBL-3 and FLC; and Moloney sarcoma virus-induced tumors. It was found that antitumor antibodies could be detected by the isotopic antiglobulin technique in these tumor systems at a relatively early stage of tumor growth. The kinetics of the antibody response in relation to the status of tumor growth varied between different tumors. In geneumor growth than in the regressors of tumor-free hosts. Reinoculation of tumor cells or recurrence of tumor growth produced elevation of antibody levels (secondary response). The specificity of the antibody reactions also varied in different tumor systems: some antibodies were truly tumor-specific and thus might produce a biological effect on in vivo tumor immunity, whereas others were not. These studies indicated that a sensitive antibody assay could be used for early detection of tumor growth. However, its usefulness in evaluation of the status of tumor growth should be carefully studied in each tumor system."} {"id": "PMID:182646", "title": "Augmented immunogenicity of tumor cell membranes produced by surface budding viruses: parameters of optimal immunization.", "content": "Membranes prepared from tumor cells infected with surface budding viruses are much more immunogenic than membranes from uninfected tumor cells. Factors affecting immunization with membranes from virus-infected tumor cells were studied. Preparations made with influenza virus were clearly superior to those prepared with vesicular stomatitis virus (VSV). Membranes infected with VSV were maximally immunogenic at a dose equivalent to a 10% cell pack whereas influenza-virus-infected membranes were immunogenic at 1/100th of this dose. Subcutaneous inoculation was better than other routes of administration. Maximum protection against challenge with viable tumor cells was afforded by two inoculations of VSV-infected membranes spaced 3 days apart or a single inoculation with influenza-virus-infected membranes. Administration of membranes in complete Freund's adjuvant either had no effect of induced a slight degree of tumor enhancement. Immunization with influenza-virus-infected membranes significantly reduced tumor size and incidence even at a challenge dose of tumor cells which was 50 times the LD100.", "contents": "Augmented immunogenicity of tumor cell membranes produced by surface budding viruses: parameters of optimal immunization. Membranes prepared from tumor cells infected with surface budding viruses are much more immunogenic than membranes from uninfected tumor cells. Factors affecting immunization with membranes from virus-infected tumor cells were studied. Preparations made with influenza virus were clearly superior to those prepared with vesicular stomatitis virus (VSV). Membranes infected with VSV were maximally immunogenic at a dose equivalent to a 10% cell pack whereas influenza-virus-infected membranes were immunogenic at 1/100th of this dose. Subcutaneous inoculation was better than other routes of administration. Maximum protection against challenge with viable tumor cells was afforded by two inoculations of VSV-infected membranes spaced 3 days apart or a single inoculation with influenza-virus-infected membranes. Administration of membranes in complete Freund's adjuvant either had no effect of induced a slight degree of tumor enhancement. Immunization with influenza-virus-infected membranes significantly reduced tumor size and incidence even at a challenge dose of tumor cells which was 50 times the LD100."} {"id": "PMID:182647", "title": "Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells.", "content": "Mechanical and enzymatic methods of disaggregating tumors were studied with the goals of (1) minimizing cell losses while (2) maintaining functional and surface membrane markers needed to objectively identify inflammatory cells (IC)1 in resultant suspensions. Application of the principles and methods described makes accurate estimation of the percentage of each IC type present in neoplasms possible for the first time. Compared to purely mechanical means of disaggregating tumors, all enzyme mixtures tested markedly increased yields of viable cells/g neoplasm. Best results were obtained with a combination of collagenase and a protease of broader substrate range (alpha chymotrypsin, papain, pronase or trypsin). The combination of enzymes that gave the highest yields with the least effect on inflammatory cell markers was trypsin, collagenase and DNAse (TCD). Because mechanical injury appeared to be the greatest single cause of cell loss (the enzymes themselves had little direct effect), potential sources were identified and either eliminated or minimized. With TCD, depending on the tumor system, cell recovery (measured as DNA recovered in cell suspensions) was as high as 50% and yields were as much as 6.9 X 10(8) viable cells/g tumor. Complete disaggregation was not required to obtain representative IC populations from tumor fragments. Neutrophils, eosinophils and mast cells from disaggregated neoplasms were counted in Giemsa stained cytocentrifuge preparations based on their unique morphologic appearances. Macrophages were identified by their capacity to phagocytose zymosan, a function which proved highly resistant to the effect of enzymes. Flourescent microscopic identification of brain associated thymus antigen (BATA) allowed quantification of T lymphocytes, since this marker was virtually unchanged by enzyme exposure. Surface immunoglobulin (Ig) was stripped from B lymphocytes most rapidly by pronase and chymotrypsin, slowly by trypsin and papain, and not at all by collagenase. Ig positive cells therefore could be quantified in suspensions generated by collagenase or very short (20 min) exposure of fragments to trypsin.", "contents": "Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. Mechanical and enzymatic methods of disaggregating tumors were studied with the goals of (1) minimizing cell losses while (2) maintaining functional and surface membrane markers needed to objectively identify inflammatory cells (IC)1 in resultant suspensions. Application of the principles and methods described makes accurate estimation of the percentage of each IC type present in neoplasms possible for the first time. Compared to purely mechanical means of disaggregating tumors, all enzyme mixtures tested markedly increased yields of viable cells/g neoplasm. Best results were obtained with a combination of collagenase and a protease of broader substrate range (alpha chymotrypsin, papain, pronase or trypsin). The combination of enzymes that gave the highest yields with the least effect on inflammatory cell markers was trypsin, collagenase and DNAse (TCD). Because mechanical injury appeared to be the greatest single cause of cell loss (the enzymes themselves had little direct effect), potential sources were identified and either eliminated or minimized. With TCD, depending on the tumor system, cell recovery (measured as DNA recovered in cell suspensions) was as high as 50% and yields were as much as 6.9 X 10(8) viable cells/g tumor. Complete disaggregation was not required to obtain representative IC populations from tumor fragments. Neutrophils, eosinophils and mast cells from disaggregated neoplasms were counted in Giemsa stained cytocentrifuge preparations based on their unique morphologic appearances. Macrophages were identified by their capacity to phagocytose zymosan, a function which proved highly resistant to the effect of enzymes. Flourescent microscopic identification of brain associated thymus antigen (BATA) allowed quantification of T lymphocytes, since this marker was virtually unchanged by enzyme exposure. Surface immunoglobulin (Ig) was stripped from B lymphocytes most rapidly by pronase and chymotrypsin, slowly by trypsin and papain, and not at all by collagenase. Ig positive cells therefore could be quantified in suspensions generated by collagenase or very short (20 min) exposure of fragments to trypsin."} {"id": "PMID:182648", "title": "Increased uptake of iodide by hormone-responsive compared to hormone-independent mammary tumors in GR mice.", "content": "The uptake of 125-iodide by transplanted hormone-responsive (HR) or hormone-independent (HI) mammary tumors, normal mammary tissue and skeletal muscle was compared in GR mice. The uptake of 125-iodide by HR mammary tumors in mice treated with progesterone and oestrone (P+O) was about 20 times greater than the uptake of 125-iodide by HI mammary tumors in mice not treated with P+O. This difference in uptake of 125-iodide by HR and HI mammary tumors could not be attributed to the difference in the hormonal status of the mice since uptake of 125-iodide was also low in HI tumors in mice receiving P+O treatment. The uptake of 125-iodide by HR mammary tumors was greatly reduced by the simultaneous injection of either an excess of non-radioactive iodide or of perchlorate. Uptake of 125-iodide by normal mammary tissue and skeletal muscle was similar was similar in all groups of tumor bearing mice, and was not influenced by the presence of an excess of non-radioactive iodide or of perchlorate. The possible clinical significance of these findings is discussed.", "contents": "Increased uptake of iodide by hormone-responsive compared to hormone-independent mammary tumors in GR mice. The uptake of 125-iodide by transplanted hormone-responsive (HR) or hormone-independent (HI) mammary tumors, normal mammary tissue and skeletal muscle was compared in GR mice. The uptake of 125-iodide by HR mammary tumors in mice treated with progesterone and oestrone (P+O) was about 20 times greater than the uptake of 125-iodide by HI mammary tumors in mice not treated with P+O. This difference in uptake of 125-iodide by HR and HI mammary tumors could not be attributed to the difference in the hormonal status of the mice since uptake of 125-iodide was also low in HI tumors in mice receiving P+O treatment. The uptake of 125-iodide by HR mammary tumors was greatly reduced by the simultaneous injection of either an excess of non-radioactive iodide or of perchlorate. Uptake of 125-iodide by normal mammary tissue and skeletal muscle was similar was similar in all groups of tumor bearing mice, and was not influenced by the presence of an excess of non-radioactive iodide or of perchlorate. The possible clinical significance of these findings is discussed."} {"id": "PMID:182649", "title": "A comparison of interhemispheric transmission times as measured by verbal and manual reaction time.", "content": "Interhemispheric transmission times (IHTTs) were calculated for 33 right-handed subjects. Verbal and manual response times (RTs) were recorded to visual stimuli exposed in either the left or right visual fields (LF, RF) for 50 msec. Each subject received 15 stimuli (dots) in the LF (1.5 degrees to the left of fixation), 15 stimuli in the RF, and 15 blank trials in both the verbal and manual response condition. IHTTs were calculated for each subject by subtracting the mean RF RT (I.E., uncrossed path) from the means LF RT (i.e., crossed path). Results indicated a nonsignificant IHTT obtained under the manual response condition of 5 msec and a highly significant IHTT obtained under the verbal response condition of 20 msec. While no significant correlation was found between IHTTs obtained under both response conditions, high correlations were found between component RT measures (i.e., manual RF RT, manual LF RT, verbal RF RT, and verbal LF RT). Thus, IHTT is independent of simple RT.", "contents": "A comparison of interhemispheric transmission times as measured by verbal and manual reaction time. Interhemispheric transmission times (IHTTs) were calculated for 33 right-handed subjects. Verbal and manual response times (RTs) were recorded to visual stimuli exposed in either the left or right visual fields (LF, RF) for 50 msec. Each subject received 15 stimuli (dots) in the LF (1.5 degrees to the left of fixation), 15 stimuli in the RF, and 15 blank trials in both the verbal and manual response condition. IHTTs were calculated for each subject by subtracting the mean RF RT (I.E., uncrossed path) from the means LF RT (i.e., crossed path). Results indicated a nonsignificant IHTT obtained under the manual response condition of 5 msec and a highly significant IHTT obtained under the verbal response condition of 20 msec. While no significant correlation was found between IHTTs obtained under both response conditions, high correlations were found between component RT measures (i.e., manual RF RT, manual LF RT, verbal RF RT, and verbal LF RT). Thus, IHTT is independent of simple RT."} {"id": "PMID:182650", "title": "The biochemistry of sugars.", "content": "In animal cells the utilization of sugars involves one or more of the three major pathways known to occur in these cells. The glycolytic (Embden-Meyerhof) pathway is quantitatively the most important, and this pathway, coupled to the citric acid cycle, serves as a major source of energy. Glycolysis and the citric acid cycle also provide most of the precursors for the synthesis of proteins, nucleic acids and lipids. The pentose phosphate, or hexose monophosphate oxidation, pathway is a major source of NADPH required for the conversion of carbohydrate to the more reduced lipids and proteins, and also furnishes the ribose and deoxyribose moieties of nucleotides and nucleic acids. The functions of the third pathway, the uronic acid pathway, are less well defined. It is the source of glucuronides for mucopolysaccharides and for detoxification mechanisms, and also in most animals, is the pathway for the synthesis of ascorbic acid. The uronic acid pathway may also function as a point of entry for glucuronides, pentoses, and pentitols.", "contents": "The biochemistry of sugars. In animal cells the utilization of sugars involves one or more of the three major pathways known to occur in these cells. The glycolytic (Embden-Meyerhof) pathway is quantitatively the most important, and this pathway, coupled to the citric acid cycle, serves as a major source of energy. Glycolysis and the citric acid cycle also provide most of the precursors for the synthesis of proteins, nucleic acids and lipids. The pentose phosphate, or hexose monophosphate oxidation, pathway is a major source of NADPH required for the conversion of carbohydrate to the more reduced lipids and proteins, and also furnishes the ribose and deoxyribose moieties of nucleotides and nucleic acids. The functions of the third pathway, the uronic acid pathway, are less well defined. It is the source of glucuronides for mucopolysaccharides and for detoxification mechanisms, and also in most animals, is the pathway for the synthesis of ascorbic acid. The uronic acid pathway may also function as a point of entry for glucuronides, pentoses, and pentitols."} {"id": "PMID:182656", "title": "Fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid of patients with central nervous system diseases.", "content": "Herpes simplex virus antibodies were studied in 73 patients with various diseases of the central nervous system. In 29 patients, there were rising titers of fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid (CSF). The CSF antibodies were predominantly IgG. In one patient, IgM was found during the fourth, but not during the eighth week of illness. The CSF antibody titers did not correlate with the serum antibody titers or with the severity of the neurologic defect. No fluorescence antibodies were found in the CSF of 52 of 53 control patients. The presence of CSF fluorescence antibodies may be of considerable value in the diagnosis of herpes simplex encephalitis. However, the absence of these antibodies in the early stage of the disease does not exclude the possibility of infection with herpes simplex virus.", "contents": "Fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid of patients with central nervous system diseases. Herpes simplex virus antibodies were studied in 73 patients with various diseases of the central nervous system. In 29 patients, there were rising titers of fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid (CSF). The CSF antibodies were predominantly IgG. In one patient, IgM was found during the fourth, but not during the eighth week of illness. The CSF antibody titers did not correlate with the serum antibody titers or with the severity of the neurologic defect. No fluorescence antibodies were found in the CSF of 52 of 53 control patients. The presence of CSF fluorescence antibodies may be of considerable value in the diagnosis of herpes simplex encephalitis. However, the absence of these antibodies in the early stage of the disease does not exclude the possibility of infection with herpes simplex virus."} {"id": "PMID:182658", "title": "[Current aspects of the pathogenesis of skin manifestations in psoriasis vulgaris].", "content": "This review deals with newer aspects of the pathogenesis of skin lesions in psoriasis vulgaris. Genetic determinants and mechanisms of provocation of psoriasis are discussed. The pathobiology of the psoriatic lesions is reviewed from a more functional point of view. The disturbances of epidermal cell proliferation and epidermal cell differentiation in the psoriatic lesions are discussed. Newer findings about chalones and the disturbances of the c-AMP/c-GMP-system are reviewed. The changes of capillaries and the inflammatory reaction in the psoriatic lesion, the morphology of the initial psoriatic lesion and newer immunological findings in patients with psoriasis are reviewed. A working hypothesis of the pathogenesis of the psoriatic lesion is given.", "contents": "[Current aspects of the pathogenesis of skin manifestations in psoriasis vulgaris]. This review deals with newer aspects of the pathogenesis of skin lesions in psoriasis vulgaris. Genetic determinants and mechanisms of provocation of psoriasis are discussed. The pathobiology of the psoriatic lesions is reviewed from a more functional point of view. The disturbances of epidermal cell proliferation and epidermal cell differentiation in the psoriatic lesions are discussed. Newer findings about chalones and the disturbances of the c-AMP/c-GMP-system are reviewed. The changes of capillaries and the inflammatory reaction in the psoriatic lesion, the morphology of the initial psoriatic lesion and newer immunological findings in patients with psoriasis are reviewed. A working hypothesis of the pathogenesis of the psoriatic lesion is given."} {"id": "PMID:182655", "title": "Radionuclide imaging of intestinal infarction in dogs.", "content": "Intestinal infarction was produced in 10 dogs by means of microsphere embolization. Intravenous and intra-arterial injections of 99mTc-pyrophosphate were then administered and in vivo and in vitro scintigrams obtained. Positive in vitro images of the infarctions were seen for all the dogs and positive in vivo radionuclide accumulation was seen for all the dogs which had intra-arterial injections. Only 1 of the 4 dogs with intravenous injection showed positive in vivo imaging of the infarction.", "contents": "Radionuclide imaging of intestinal infarction in dogs. Intestinal infarction was produced in 10 dogs by means of microsphere embolization. Intravenous and intra-arterial injections of 99mTc-pyrophosphate were then administered and in vivo and in vitro scintigrams obtained. Positive in vitro images of the infarctions were seen for all the dogs and positive in vivo radionuclide accumulation was seen for all the dogs which had intra-arterial injections. Only 1 of the 4 dogs with intravenous injection showed positive in vivo imaging of the infarction."} {"id": "PMID:182659", "title": "Correlative morphological and biochemical study of the effects of isoprenaline on the organelle and membrane content of the rabbit parotid gland.", "content": "A quantitative study has been made on the enzymic, chemical and ultrastructural changes that occur in the parotid glands of rabbits as a result of Isoprenaline-induced secretion. Emphasis has been placed on correlating changes in organelle and membrane content which are evident 2 hr after Isoprenaline administration and which have been measured stereologically with the levels of appropriate enzymic or chemical markers, taking into account the contribution made by both the acinar and duct tissue. Lower protein, alpha-amylase and beta-glycerophosphatase levels correlated with reductions in zymogen granule and lysosome volume with whilst plasmalemmal and Golgi membrane areas and their marker enzyme concentrations remained unchanged. However, declines in alkaline phosphatase and succinate dehydrogenase activity (illustrated histochemically), and p-nitrophenyl phosphatase activity at pH 4-5 in the presence of tartrate occurred without any detectable decrease in membrane area. Conversely, an increase in rough endoplasmic reticulum area was measured stereologically but no increases in chemical markers were detected. The extent of correlation of the data is discussed in the context of the mechanism of secretion and the action of Isoprenaline.", "contents": "Correlative morphological and biochemical study of the effects of isoprenaline on the organelle and membrane content of the rabbit parotid gland. A quantitative study has been made on the enzymic, chemical and ultrastructural changes that occur in the parotid glands of rabbits as a result of Isoprenaline-induced secretion. Emphasis has been placed on correlating changes in organelle and membrane content which are evident 2 hr after Isoprenaline administration and which have been measured stereologically with the levels of appropriate enzymic or chemical markers, taking into account the contribution made by both the acinar and duct tissue. Lower protein, alpha-amylase and beta-glycerophosphatase levels correlated with reductions in zymogen granule and lysosome volume with whilst plasmalemmal and Golgi membrane areas and their marker enzyme concentrations remained unchanged. However, declines in alkaline phosphatase and succinate dehydrogenase activity (illustrated histochemically), and p-nitrophenyl phosphatase activity at pH 4-5 in the presence of tartrate occurred without any detectable decrease in membrane area. Conversely, an increase in rough endoplasmic reticulum area was measured stereologically but no increases in chemical markers were detected. The extent of correlation of the data is discussed in the context of the mechanism of secretion and the action of Isoprenaline."} {"id": "PMID:182660", "title": "Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study to differentiate the enzymes involved.", "content": "The purpose of this study was to try to differentiate histochemically between the various enzymes which may catalyze the hydrolysis of ATP in developing rat dental tissues. Freeze cut and freeze dried sections of molar and incisor teeth were incubated in lead capture-based media at pH 5.0, 7.2 or 9.4 with one of the following substrates: beta-glycerophosphate, AMP, ADP, ATP, AMP-PNP and tetrasodium pyrophosphate. To establish the enzymatic nature of the hydrolysis parallel sections were incubated after prior fixation in either formaldehyde or glutaraldehyde. By comparing the enzymatic stainings obtained with the various substrates and at the different pH:s, it was concluded that ATP can be visibly hydrolyzed in rat dental tissues by alkaline phosphatase (stratum intermedium, apical part of maturation ameloblasts, basal part of all ameloblasts, odontoblasts and subodontoblastic layer), specific ATPase (apical and basal parts of secretory ameloblasts) and ATP pyrophosphatase and/or adenylate cyclase (stratum intermedium, odontoblasts). Acid phosphatase, specific ADPase, 5'-nucleotidase, inorganic pyrophosphatase, 3':5'-cyclic-AMP-phosphodiesterase and adenylate kinase on the other hand, seem not to be engaged in the ATP hydrolysis to such a degree as to complicate the interpretation of the histochemical staining. The alkaline phosphatase part of the ATP hydrolysis appeared to be rather insensitive to aldehyde fixation, while the hydrolysis effected by specific ATPase and ATP pyrophosphatase and/or adenylate cyclase was extinguished after fixation with formaldehyde for 4 h or glutaraldehyde for 10 min.", "contents": "Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study to differentiate the enzymes involved. The purpose of this study was to try to differentiate histochemically between the various enzymes which may catalyze the hydrolysis of ATP in developing rat dental tissues. Freeze cut and freeze dried sections of molar and incisor teeth were incubated in lead capture-based media at pH 5.0, 7.2 or 9.4 with one of the following substrates: beta-glycerophosphate, AMP, ADP, ATP, AMP-PNP and tetrasodium pyrophosphate. To establish the enzymatic nature of the hydrolysis parallel sections were incubated after prior fixation in either formaldehyde or glutaraldehyde. By comparing the enzymatic stainings obtained with the various substrates and at the different pH:s, it was concluded that ATP can be visibly hydrolyzed in rat dental tissues by alkaline phosphatase (stratum intermedium, apical part of maturation ameloblasts, basal part of all ameloblasts, odontoblasts and subodontoblastic layer), specific ATPase (apical and basal parts of secretory ameloblasts) and ATP pyrophosphatase and/or adenylate cyclase (stratum intermedium, odontoblasts). Acid phosphatase, specific ADPase, 5'-nucleotidase, inorganic pyrophosphatase, 3':5'-cyclic-AMP-phosphodiesterase and adenylate kinase on the other hand, seem not to be engaged in the ATP hydrolysis to such a degree as to complicate the interpretation of the histochemical staining. The alkaline phosphatase part of the ATP hydrolysis appeared to be rather insensitive to aldehyde fixation, while the hydrolysis effected by specific ATPase and ATP pyrophosphatase and/or adenylate cyclase was extinguished after fixation with formaldehyde for 4 h or glutaraldehyde for 10 min."} {"id": "PMID:182661", "title": "The demonstration of acid phosphatase in cultured 3T3 mouse cells.", "content": "Acid phosphatase has been demonstrated ultrastructurally in 3T3 and SV40-3T3 mouse cells using sodium beta-glycerophosphate and p-nitrophenyl phosphate as substrate. The former substrate only demonstrates the enzyme in lysosomes and elements of the Golgi apparatus while the latter demonstrates it in the cisternae of the endoplasmic reticulum and in the cell surface as well as at lysosomal sites. The significance of surface acid phosphatase activity is discussed in terms of sublethal autolysis.", "contents": "The demonstration of acid phosphatase in cultured 3T3 mouse cells. Acid phosphatase has been demonstrated ultrastructurally in 3T3 and SV40-3T3 mouse cells using sodium beta-glycerophosphate and p-nitrophenyl phosphate as substrate. The former substrate only demonstrates the enzyme in lysosomes and elements of the Golgi apparatus while the latter demonstrates it in the cisternae of the endoplasmic reticulum and in the cell surface as well as at lysosomal sites. The significance of surface acid phosphatase activity is discussed in terms of sublethal autolysis."} {"id": "PMID:182662", "title": "[Childhood facial paralysis due to tumours (author's transl)].", "content": "Facial nerve palsy due to malignant tumours is uncommon in childhood and adolescence. If present the malignancy may be primary or metastatic, and usually brain tumours, leukaemias, or lymphosarcomas are found. Rhabdomyosarcomas, parotid malignancies, Ewing's sarcomas, Wilms' tumours and neuroblastomas are rare. The nerve lesion may be due to direct tumour infiltration, external pressure on the nerve and secondary ischaemia. In disseminated malignancy the lesion is usually due to extending intraneural infiltration and all parts of the nerve may be affected. If facial nerve palsy coexists the prognosis in childhood malignancies is extremely poor.", "contents": "[Childhood facial paralysis due to tumours (author's transl)]. Facial nerve palsy due to malignant tumours is uncommon in childhood and adolescence. If present the malignancy may be primary or metastatic, and usually brain tumours, leukaemias, or lymphosarcomas are found. Rhabdomyosarcomas, parotid malignancies, Ewing's sarcomas, Wilms' tumours and neuroblastomas are rare. The nerve lesion may be due to direct tumour infiltration, external pressure on the nerve and secondary ischaemia. In disseminated malignancy the lesion is usually due to extending intraneural infiltration and all parts of the nerve may be affected. If facial nerve palsy coexists the prognosis in childhood malignancies is extremely poor."} {"id": "PMID:182663", "title": "Evidences for complex formation between polymyxin B and lipopolysaccharides from Serratia marcescens.", "content": "In vitro and in vivo complex formations of polymyxin B and lipopolysaccharides (LPS) from resistant and sensitive cells of Serratia marcescens were studied by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and electron microscopy. In vitro treatment of LPS from resistant cells with polymyxin B gave two populations of spherical complexes of differnt molecular weights as determined electrophoretically. Similar treatment of LPS from sensitive cells resulted in dissociation of the LPS-protein and subsequent complexing with the LPS moiety into stable spheres. In vivo treatment of resistant cells with polymyxin B resulted in LPS-polymyxin B complexes which were comparatively smaller and existed in two morphological forms; spheres and linear ribbons. LPS from the sensitive cells were degraded extensively into small rods and an amorphous mass by the in vivo polymyxin B treatment. In both systems, the electrophoretic results consistently matched the electron microscopic evidences for complex formation of LPS with polymyxin B. It is suggested that the disruptive effects of polymyxin B on LPS in the outer membrane of S. marcescens may be the explanation for the change in permeability barrier in the resistant cells and disorganization of the outer membrane and subsequent death in the sensitive cells. Furthermore, the ability of the LPS to complex with the polymyxin B molecules in resistant cells may be the basis of their resistance to the antibiotic.", "contents": "Evidences for complex formation between polymyxin B and lipopolysaccharides from Serratia marcescens. In vitro and in vivo complex formations of polymyxin B and lipopolysaccharides (LPS) from resistant and sensitive cells of Serratia marcescens were studied by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and electron microscopy. In vitro treatment of LPS from resistant cells with polymyxin B gave two populations of spherical complexes of differnt molecular weights as determined electrophoretically. Similar treatment of LPS from sensitive cells resulted in dissociation of the LPS-protein and subsequent complexing with the LPS moiety into stable spheres. In vivo treatment of resistant cells with polymyxin B resulted in LPS-polymyxin B complexes which were comparatively smaller and existed in two morphological forms; spheres and linear ribbons. LPS from the sensitive cells were degraded extensively into small rods and an amorphous mass by the in vivo polymyxin B treatment. In both systems, the electrophoretic results consistently matched the electron microscopic evidences for complex formation of LPS with polymyxin B. It is suggested that the disruptive effects of polymyxin B on LPS in the outer membrane of S. marcescens may be the explanation for the change in permeability barrier in the resistant cells and disorganization of the outer membrane and subsequent death in the sensitive cells. Furthermore, the ability of the LPS to complex with the polymyxin B molecules in resistant cells may be the basis of their resistance to the antibiotic."} {"id": "PMID:182666", "title": "Effect of increased gas density on pulmonary gas exchange in man.", "content": "Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.", "contents": "Effect of increased gas density on pulmonary gas exchange in man. Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men."} {"id": "PMID:182667", "title": "Manganese requirement of phosphoglycerate phosphomutase and its consequences for growth and sporulation of Bacillus subtilis.", "content": "In the absence of manganese, rapidly metabolizable carbohydrates such as glucose or glycerol are not completely metabolized by Bacillus subtilis growing in a nutrient sporulation medium: 3-phosphoglyceric acid (3PGA) accumulates inside the cells, growth stops at a low cell titer, and normal sporulation remains suppressed (no prespore septa). Upon the addition of manganese, 3PGA disappears, growth resumes, and normal sporulation takes place. These effects results from a specific manganese requirement of phosphoglycerate phosphomutase which catalyzes the interconversion of 3PGA and 2-phosphoglyceric acid (2PGA). Other metal ions cannot replace manganese, for which the enzyme has an apparent Km of 0.22 mM.", "contents": "Manganese requirement of phosphoglycerate phosphomutase and its consequences for growth and sporulation of Bacillus subtilis. In the absence of manganese, rapidly metabolizable carbohydrates such as glucose or glycerol are not completely metabolized by Bacillus subtilis growing in a nutrient sporulation medium: 3-phosphoglyceric acid (3PGA) accumulates inside the cells, growth stops at a low cell titer, and normal sporulation remains suppressed (no prespore septa). Upon the addition of manganese, 3PGA disappears, growth resumes, and normal sporulation takes place. These effects results from a specific manganese requirement of phosphoglycerate phosphomutase which catalyzes the interconversion of 3PGA and 2-phosphoglyceric acid (2PGA). Other metal ions cannot replace manganese, for which the enzyme has an apparent Km of 0.22 mM."} {"id": "PMID:182668", "title": "Arginine, a growth-limiting factor for Eubacterium lentum.", "content": "Eubacterium lentum is a gram-positive, asaccharolytic, obligately anaerobic bacillus, which grows to a low turbidity (absorbancy at 650 nm = 0.05 to 0.1) in peptone-based medium. The addition of substrate amounts of arginine or citrulline dramatically increased growth (absorbancy at 650 nm =1.4). The presence of an arginine dihydrolase pathway was confirmed by measurement of the necessary enzymes and demonstration of the intermediate compounds. The production of adenosine 5'-triphosphate from the arginine dihydrolase pathway appeared to be the sole source of energy for growth of this organism. Each of 11 strains showed definite growth stimulation. Ten of the 11 strains had cytochromes. Growth stimulation with arginine and the presence of cytochromes offer two new positive criteria for the identification of E. lentum.", "contents": "Arginine, a growth-limiting factor for Eubacterium lentum. Eubacterium lentum is a gram-positive, asaccharolytic, obligately anaerobic bacillus, which grows to a low turbidity (absorbancy at 650 nm = 0.05 to 0.1) in peptone-based medium. The addition of substrate amounts of arginine or citrulline dramatically increased growth (absorbancy at 650 nm =1.4). The presence of an arginine dihydrolase pathway was confirmed by measurement of the necessary enzymes and demonstration of the intermediate compounds. The production of adenosine 5'-triphosphate from the arginine dihydrolase pathway appeared to be the sole source of energy for growth of this organism. Each of 11 strains showed definite growth stimulation. Ten of the 11 strains had cytochromes. Growth stimulation with arginine and the presence of cytochromes offer two new positive criteria for the identification of E. lentum."} {"id": "PMID:182669", "title": "Soluble adenylate cyclase from the culture medium of Bordetella pertussis: purification and characterization.", "content": "Culture medium of exponentially growing Bordetella pertussis (strain 114) contains significant quantities of soluble (100,000 X g for 1 h) adenylate cyclase. The enzyme was purified by chromatography on diethylaminoethyl-cellulose and Sephadex G-200. The purest material yielded a single band on sodium dodecyl sulfate-disc gel electrophoresis. It is heat labile, has a temperature optimum of 30 degrees C, a pH optimum of pH 7 to 8, and a Km for adenosine 5'-triphosphate of 0.4 mM, and requires Mg2+ for maximum activity. The molecular weight, by sodium dodecyl sulfate-disc gel electrophoresis and sucrose density gradient, is approximately 70,000. The enzyme is markedly inhibited by fluoride and weakly inhibited by monovalent salts, but its activity is not altered by alpha-keto acids of nonsubstrate nucleoside triphosphates. Thus, but its presence in the culture supernatant, its smaller molecular weight, and its insensitivity to alpha-keto acids and nucleotides, this enzyme differs from the bacterial adenylate cyclases previously described.", "contents": "Soluble adenylate cyclase from the culture medium of Bordetella pertussis: purification and characterization. Culture medium of exponentially growing Bordetella pertussis (strain 114) contains significant quantities of soluble (100,000 X g for 1 h) adenylate cyclase. The enzyme was purified by chromatography on diethylaminoethyl-cellulose and Sephadex G-200. The purest material yielded a single band on sodium dodecyl sulfate-disc gel electrophoresis. It is heat labile, has a temperature optimum of 30 degrees C, a pH optimum of pH 7 to 8, and a Km for adenosine 5'-triphosphate of 0.4 mM, and requires Mg2+ for maximum activity. The molecular weight, by sodium dodecyl sulfate-disc gel electrophoresis and sucrose density gradient, is approximately 70,000. The enzyme is markedly inhibited by fluoride and weakly inhibited by monovalent salts, but its activity is not altered by alpha-keto acids of nonsubstrate nucleoside triphosphates. Thus, but its presence in the culture supernatant, its smaller molecular weight, and its insensitivity to alpha-keto acids and nucleotides, this enzyme differs from the bacterial adenylate cyclases previously described."} {"id": "PMID:182670", "title": "Use of polymyxin B, levallorphan, and tetracaine to isolate novel envelope mutants of Escherichia coli.", "content": "Mutants of Escherichia coli were isolated by their resistance to the bacteriocidal effects of the membrane-active drugs polymyxin B, levallorphan, and tetracaine. The mutants were examined for additional changes in cellular physiology evoked by the lesions; many polymyxin-resistant strains had a concomitant increased sensitivity to anionic detergents, and several strains of each type had concomitant alterations in generation time and morphology. Mutants of each class (polymyxin resistant, tetracaine resistant, and levallorphan resistant) were transduced into recipient strains. The levallorphan resistance site (lev) was located at approximately 9 min on the E. coli chromosome. Polymyxin (pmx) and tetracaine (tec) resistance loci were also transduced. The lev and tec strains had a slight prolongation of generation time, in contrast with their isogenic wild-type strains. The tec transductant produced long filaments in the absence of tetracaine and had an altered colonial morphology, it reverted at high frequency, with the morphological abnormalities reverting along with the tetracaine resistance. The pmx transductant had an increased sensitivity to levallorphan and to anionic detergents. In contrast, both lev and tec mutants were more resistant to acriflavine than was the wild type or the pmx transductant. The pmx, lev, and tec loci differed in sensitivity to mitomycin C; the lev strain was more resistant, the tec strain was more sensitive, and the pmx strain was much more sensitive than the wild type. There was no difference in sensitivity to several other dyes and detergents, colicins, or T bacteriophage between the transductant and isogenic wild-type strains. Thus, lev, tec, and pmx loci confer more subtle alterations in the permeability barrier than do lipopolysaccharide-deficient mutants previously studied.", "contents": "Use of polymyxin B, levallorphan, and tetracaine to isolate novel envelope mutants of Escherichia coli. Mutants of Escherichia coli were isolated by their resistance to the bacteriocidal effects of the membrane-active drugs polymyxin B, levallorphan, and tetracaine. The mutants were examined for additional changes in cellular physiology evoked by the lesions; many polymyxin-resistant strains had a concomitant increased sensitivity to anionic detergents, and several strains of each type had concomitant alterations in generation time and morphology. Mutants of each class (polymyxin resistant, tetracaine resistant, and levallorphan resistant) were transduced into recipient strains. The levallorphan resistance site (lev) was located at approximately 9 min on the E. coli chromosome. Polymyxin (pmx) and tetracaine (tec) resistance loci were also transduced. The lev and tec strains had a slight prolongation of generation time, in contrast with their isogenic wild-type strains. The tec transductant produced long filaments in the absence of tetracaine and had an altered colonial morphology, it reverted at high frequency, with the morphological abnormalities reverting along with the tetracaine resistance. The pmx transductant had an increased sensitivity to levallorphan and to anionic detergents. In contrast, both lev and tec mutants were more resistant to acriflavine than was the wild type or the pmx transductant. The pmx, lev, and tec loci differed in sensitivity to mitomycin C; the lev strain was more resistant, the tec strain was more sensitive, and the pmx strain was much more sensitive than the wild type. There was no difference in sensitivity to several other dyes and detergents, colicins, or T bacteriophage between the transductant and isogenic wild-type strains. Thus, lev, tec, and pmx loci confer more subtle alterations in the permeability barrier than do lipopolysaccharide-deficient mutants previously studied."} {"id": "PMID:182671", "title": "Electron microscope study of sporulation and parasporal crystal formation in Bacillus thuringiensis.", "content": "A comprehensive ultrastructural analysis of sporulation and parasporal crystal development is described for Bacillus thuringiensis. The insecticidal crystal of B. thuringiensis is initiated at the start of engulfment and is nearly complete by the time the exosporium forms. The crystal and a heretofore unobserved ovoid inclusion develop without any clear association with the forespore septum, exosporium, or mesosomes. These observations contradict previous hypotheses that the crystal is synthesized on the forespore membrane, exosporium, or mesosomes. Formation of forespore septa involves densely staining, double-membrane-bound, vesicular mesosomes that have a bridged appearance. Forespore engulfment is subpolar and also involves mesosomes. Upon completion of engulfment and the following cytoplasmic changes occur: decrease in electron density of the incipient forespore membrane; loss of bridged appearance of incipient forespore membrane; change in stainability of incipient forespore, forespore, and mother cell cytoplasms; and alteration in staining quality of plasma membrane. These changes are involved in the conversion of the incipient forespore into a forespore and reflect \"commitment\" to sporulation.", "contents": "Electron microscope study of sporulation and parasporal crystal formation in Bacillus thuringiensis. A comprehensive ultrastructural analysis of sporulation and parasporal crystal development is described for Bacillus thuringiensis. The insecticidal crystal of B. thuringiensis is initiated at the start of engulfment and is nearly complete by the time the exosporium forms. The crystal and a heretofore unobserved ovoid inclusion develop without any clear association with the forespore septum, exosporium, or mesosomes. These observations contradict previous hypotheses that the crystal is synthesized on the forespore membrane, exosporium, or mesosomes. Formation of forespore septa involves densely staining, double-membrane-bound, vesicular mesosomes that have a bridged appearance. Forespore engulfment is subpolar and also involves mesosomes. Upon completion of engulfment and the following cytoplasmic changes occur: decrease in electron density of the incipient forespore membrane; loss of bridged appearance of incipient forespore membrane; change in stainability of incipient forespore, forespore, and mother cell cytoplasms; and alteration in staining quality of plasma membrane. These changes are involved in the conversion of the incipient forespore into a forespore and reflect \"commitment\" to sporulation."} {"id": "PMID:182672", "title": "Genetic control of the glp system in Bacillus subtilis.", "content": "In pleiotropic negative glycerol utilization mutants (GlpPI mutants) of Bacillus subitilis, glycerol kinase and sn-glycerol 3-phosphate (G3P) dehydrogenase are noninducible. GlpPI mutants also fail to take up exogenous [14C]G3P. To study the regulation of the glp system in B. subtilis phenotypically, Glp+ revertants were isolated from GlpPI mutants. Four classes of revertants were identified: phenotypically, wild type; R1 type, which contains an informational suppressor, R2 type, which produced G3P dehydrogenase constitutively; and R3 type, with a temperature-sensitive Glp phenotype producing G3P dehydrogenase constitutively at permissive temperature (32 degrees C). The properties of the revertants indicate that the glpPI locus codes for a protein with a positive regulatory function.", "contents": "Genetic control of the glp system in Bacillus subtilis. In pleiotropic negative glycerol utilization mutants (GlpPI mutants) of Bacillus subitilis, glycerol kinase and sn-glycerol 3-phosphate (G3P) dehydrogenase are noninducible. GlpPI mutants also fail to take up exogenous [14C]G3P. To study the regulation of the glp system in B. subtilis phenotypically, Glp+ revertants were isolated from GlpPI mutants. Four classes of revertants were identified: phenotypically, wild type; R1 type, which contains an informational suppressor, R2 type, which produced G3P dehydrogenase constitutively; and R3 type, with a temperature-sensitive Glp phenotype producing G3P dehydrogenase constitutively at permissive temperature (32 degrees C). The properties of the revertants indicate that the glpPI locus codes for a protein with a positive regulatory function."} {"id": "PMID:182673", "title": "Effect of chloramphenicol on the electron systems in Ustilago cynodontis.", "content": "The mycelial cells of Ustilago cynodontis possess at least two electron transport systems: a cyanide-sensitive cytochrome pathway, which represents the major route for electron transport, and an alternative cyanide-insensitive pathway, inhibited by salicylhydroxamic acid. In the presence of chloramphenicol in the culture medium, mycelial cells respire only by the alternatuve chain. The stable induced yeast-like cells, obtained by prolonged chloramphenicol treatment of the mycelial cells, respire as the untreated mycelial cells; this result indicates that the phenotypic change induced by chloramphenicol is not related to a modification of the respiratory system.", "contents": "Effect of chloramphenicol on the electron systems in Ustilago cynodontis. The mycelial cells of Ustilago cynodontis possess at least two electron transport systems: a cyanide-sensitive cytochrome pathway, which represents the major route for electron transport, and an alternative cyanide-insensitive pathway, inhibited by salicylhydroxamic acid. In the presence of chloramphenicol in the culture medium, mycelial cells respire only by the alternatuve chain. The stable induced yeast-like cells, obtained by prolonged chloramphenicol treatment of the mycelial cells, respire as the untreated mycelial cells; this result indicates that the phenotypic change induced by chloramphenicol is not related to a modification of the respiratory system."} {"id": "PMID:182674", "title": "Membrane-bound respiratory of Spirillum itersonii.", "content": "The membrane-bound respiratory system of the gram-negative bacterium Spirillum itersonii was investigated. It contains cytochromes b (558), c (550), and o (558) and beta-dihydro-nicotinamide adenine dinucleotide (NADH) and succinate oxidase activities under all growth conditions. It is also capable of producing D-lactate and alpha-glycerophosphate dehydrogenases when grown with lactate or glycerol as sole carbon source. Membrane-bound malate dehydrogenase was not detectable under any conditions, although there is high activity of soluble nicotinamide adenine dinucleotide: malate dehydrogenase. When grown with oxygen as the sole terminal electron acceptor, approximately 60% of the total b-type cytochrome is present as cytochrome o, whereas only 40% is present as cytochrome o in cells grown with nitrate in the presence of oxygen. Both NADH and succinate oxidase are inhibited by azide, cyanide, antimycin A, and 2-n-heptyl-4-hydroxyquinoline-N-oxidase at low concentrations. The ability of these inhibitors to completely inhibit oxidase activity at low concentrations and their effects upon the aerobic steady-state reduction levels of b- and c-type cytochromes as well as the aerobic steady-state reduction levels obtained with NADH, succinate, and ascorbate-dichlorophenolindophenol suggest that presence of an unbranched respiratory chain in S. itersonii with the order ubiquinone leads to b leads to c leads to c leads to oxygen.", "contents": "Membrane-bound respiratory of Spirillum itersonii. The membrane-bound respiratory system of the gram-negative bacterium Spirillum itersonii was investigated. It contains cytochromes b (558), c (550), and o (558) and beta-dihydro-nicotinamide adenine dinucleotide (NADH) and succinate oxidase activities under all growth conditions. It is also capable of producing D-lactate and alpha-glycerophosphate dehydrogenases when grown with lactate or glycerol as sole carbon source. Membrane-bound malate dehydrogenase was not detectable under any conditions, although there is high activity of soluble nicotinamide adenine dinucleotide: malate dehydrogenase. When grown with oxygen as the sole terminal electron acceptor, approximately 60% of the total b-type cytochrome is present as cytochrome o, whereas only 40% is present as cytochrome o in cells grown with nitrate in the presence of oxygen. Both NADH and succinate oxidase are inhibited by azide, cyanide, antimycin A, and 2-n-heptyl-4-hydroxyquinoline-N-oxidase at low concentrations. The ability of these inhibitors to completely inhibit oxidase activity at low concentrations and their effects upon the aerobic steady-state reduction levels of b- and c-type cytochromes as well as the aerobic steady-state reduction levels obtained with NADH, succinate, and ascorbate-dichlorophenolindophenol suggest that presence of an unbranched respiratory chain in S. itersonii with the order ubiquinone leads to b leads to c leads to c leads to oxygen."} {"id": "PMID:182675", "title": "Effect of polymyxin on the ultrastructure of the outer membrane of wild-type and polymyxin-resistant strain of Salmonella.", "content": "The effect of polymyxin on two sets of Salmonella mutants was studied by thin-section and scanning electron microscopy. Polymyxin (in increasing concentrations, starting just below bactericidal effect) caused the appearance of the previously described rodlike projections on the cell surface of wild-type (smooth, polymyxin-sensitive) bacteria. These projections seemed to involve the outer membrane of the cell wall. In rough mutants, which are deficient in lipopolysaccharide, the projections were much smaller and flat. Higher concentrations of polymyxin were required to produce morphological effects in polyxmin-resistant mutants of both smooth and rough forms. Furthermore, in these mutants polymyxin caused vesicle-like bulging of the total outer membrane quite different in appearance from the rodlike projections of the wild type.", "contents": "Effect of polymyxin on the ultrastructure of the outer membrane of wild-type and polymyxin-resistant strain of Salmonella. The effect of polymyxin on two sets of Salmonella mutants was studied by thin-section and scanning electron microscopy. Polymyxin (in increasing concentrations, starting just below bactericidal effect) caused the appearance of the previously described rodlike projections on the cell surface of wild-type (smooth, polymyxin-sensitive) bacteria. These projections seemed to involve the outer membrane of the cell wall. In rough mutants, which are deficient in lipopolysaccharide, the projections were much smaller and flat. Higher concentrations of polymyxin were required to produce morphological effects in polyxmin-resistant mutants of both smooth and rough forms. Furthermore, in these mutants polymyxin caused vesicle-like bulging of the total outer membrane quite different in appearance from the rodlike projections of the wild type."} {"id": "PMID:182676", "title": "Growth inhibition of Proteus mirabilis by cyclic adenosine 3'-5'-monophosphate.", "content": "Growth of Proteus mirabilis on a synthetic agar medium containing either glycerol, galactose, or trehalose as the sole source is inhibited by 5 mM cyclic adenosine 3',5'-monophosphate (cAMP). Inhibition on an agar medium is evident as loss of viability, but in broth cAMP only slightly inhibits growth rate. Inhibition is associated with the accumulation of methylglyoxal in the medium. A nonswarming mutant of P. mirabilis is not inhibited by cAMP on either of the three carbon sources, but it is sensitive to exogenous methylglyoxal.", "contents": "Growth inhibition of Proteus mirabilis by cyclic adenosine 3'-5'-monophosphate. Growth of Proteus mirabilis on a synthetic agar medium containing either glycerol, galactose, or trehalose as the sole source is inhibited by 5 mM cyclic adenosine 3',5'-monophosphate (cAMP). Inhibition on an agar medium is evident as loss of viability, but in broth cAMP only slightly inhibits growth rate. Inhibition is associated with the accumulation of methylglyoxal in the medium. A nonswarming mutant of P. mirabilis is not inhibited by cAMP on either of the three carbon sources, but it is sensitive to exogenous methylglyoxal."} {"id": "PMID:182677", "title": "New radioisotopic assays of argininosuccinate synthetase and argininosuccinase.", "content": "Methods were developed for the radioisotopic assay of argininosuccinate synthetase [L-citrulline: L-aspartate ligase (AMP-forming), EC 6.3.4.5] and argininosuccinase [L-argininosuccinate arginine-lyase, EC 4.3.2.1]. The assay of argininosuccinate synthetase was based on the separation of [14C]argininosuccinate formed from aspartate and [carbamoyl-14C]citrulline in the presence of ATP from the substrate citrulline. For this, the product was converted to its anhydride form by boiling for 30 min at pH 2.0 followed by application on a column of Dowex 50W (pyridine form). Argininosuccinic anhydride was eluted with 0.3 M pyridine acetate buffer, pH 4.25, while citrulline was eluted with 0.1 M pyridine acetate buffer, pH 3.80. The assay of argininosuccinase was based on the separation of [14C]argininosuccinic acid formed from arginine and [U-14C]fumaric acid from the substrate fumarate on a column of Dowex 50W(H+ form). The argininosuccinic acid was adsorbed on the column and eluted with 1 M pyridine solution, while fumarate was not adsorbed. The distributions of these two enzymes in various organs and cell fractions were reinvestigated using these methods.", "contents": "New radioisotopic assays of argininosuccinate synthetase and argininosuccinase. Methods were developed for the radioisotopic assay of argininosuccinate synthetase [L-citrulline: L-aspartate ligase (AMP-forming), EC 6.3.4.5] and argininosuccinase [L-argininosuccinate arginine-lyase, EC 4.3.2.1]. The assay of argininosuccinate synthetase was based on the separation of [14C]argininosuccinate formed from aspartate and [carbamoyl-14C]citrulline in the presence of ATP from the substrate citrulline. For this, the product was converted to its anhydride form by boiling for 30 min at pH 2.0 followed by application on a column of Dowex 50W (pyridine form). Argininosuccinic anhydride was eluted with 0.3 M pyridine acetate buffer, pH 4.25, while citrulline was eluted with 0.1 M pyridine acetate buffer, pH 3.80. The assay of argininosuccinase was based on the separation of [14C]argininosuccinic acid formed from arginine and [U-14C]fumaric acid from the substrate fumarate on a column of Dowex 50W(H+ form). The argininosuccinic acid was adsorbed on the column and eluted with 1 M pyridine solution, while fumarate was not adsorbed. The distributions of these two enzymes in various organs and cell fractions were reinvestigated using these methods."} {"id": "PMID:182678", "title": "Purification and characterization of human leukocyte interferon components.", "content": "Human leukocyte interferon, prepurified either by acid ethanol extraction or by affinity chromatography with antibodies, was further purified by gel filtration in the presence of sodium dodecyl sulfate. Interferon was eluted from gel filtration columns as an apparently homogeneous entity with a molecular weight of 26,600, resulting in an up to 50-fold additional purification during a single step. The antiviral activity could be further resolved into two components by hydroxylapatite adsorption chromatography. The isolated components (A and B) were distinguishable by isoelectric focusing and polyacrylamide gel electrophoresis. The apparent molecular weights were 20,000 to 16,000 and 16,000, respectively. No differences were detected in their susceptibility toward reduction of disulfide bonds by beta-mercaptoethanol. Both could be obtained on a preparative scale with minimal losses in biological activity.", "contents": "Purification and characterization of human leukocyte interferon components. Human leukocyte interferon, prepurified either by acid ethanol extraction or by affinity chromatography with antibodies, was further purified by gel filtration in the presence of sodium dodecyl sulfate. Interferon was eluted from gel filtration columns as an apparently homogeneous entity with a molecular weight of 26,600, resulting in an up to 50-fold additional purification during a single step. The antiviral activity could be further resolved into two components by hydroxylapatite adsorption chromatography. The isolated components (A and B) were distinguishable by isoelectric focusing and polyacrylamide gel electrophoresis. The apparent molecular weights were 20,000 to 16,000 and 16,000, respectively. No differences were detected in their susceptibility toward reduction of disulfide bonds by beta-mercaptoethanol. Both could be obtained on a preparative scale with minimal losses in biological activity."} {"id": "PMID:182679", "title": "Hypoxanthine transport by cultured Chinese hamster lung fibroblasts.", "content": "The uptake of hypoxanthine by Chinese hamster lung fibroblasts grown in tissue culture was studied in wild type clones and 8-azaguanine-resistant mutant clones devoid of hypoxanthine-guanine phosphoribosyltransferase. Wild type fibroblasts rapidly accumulate [3H]hypoxanthine from the medium and over 80% of the intracellular radioactivity is found in acid-soluble nucleotides. The phosphoribosyltransferase-deficient clones accumulate much lower levels of hypoxanthine and over 85% of the intracellular 3H label is associated with chemically unaltered hypoxanthine. The internal level of hypoxanthine in the mutant clones rapidly approaches but does not exceed that present in the medium. Wild type and phosphoribosyltransferase-deficient cells take up hypoxanthine at almost identical initial rates at external hypoxanthine levels from 2 to 300 muM. Analysis of these data reveals two transport systems that obey the Michaelis-Menten relationship. These differ markedly in affinity, yielding average Km values of 20 and 600 muM for both cell types. Hypoxanthine transport by both low and high affinity transport systems is blocked by p-chloromercuriphenylsulfonate and N-ethylmaleimide. Counter-transport of hypoxanthine was demonstrated in phosphoribosyltransferase-deficient fibroblasts. It is concluded that hypoxanthine is transported into Chinese hamster cells by means of carrier-mediated processes (facilitated diffusion) that operate independently of phosphoribosylation.", "contents": "Hypoxanthine transport by cultured Chinese hamster lung fibroblasts. The uptake of hypoxanthine by Chinese hamster lung fibroblasts grown in tissue culture was studied in wild type clones and 8-azaguanine-resistant mutant clones devoid of hypoxanthine-guanine phosphoribosyltransferase. Wild type fibroblasts rapidly accumulate [3H]hypoxanthine from the medium and over 80% of the intracellular radioactivity is found in acid-soluble nucleotides. The phosphoribosyltransferase-deficient clones accumulate much lower levels of hypoxanthine and over 85% of the intracellular 3H label is associated with chemically unaltered hypoxanthine. The internal level of hypoxanthine in the mutant clones rapidly approaches but does not exceed that present in the medium. Wild type and phosphoribosyltransferase-deficient cells take up hypoxanthine at almost identical initial rates at external hypoxanthine levels from 2 to 300 muM. Analysis of these data reveals two transport systems that obey the Michaelis-Menten relationship. These differ markedly in affinity, yielding average Km values of 20 and 600 muM for both cell types. Hypoxanthine transport by both low and high affinity transport systems is blocked by p-chloromercuriphenylsulfonate and N-ethylmaleimide. Counter-transport of hypoxanthine was demonstrated in phosphoribosyltransferase-deficient fibroblasts. It is concluded that hypoxanthine is transported into Chinese hamster cells by means of carrier-mediated processes (facilitated diffusion) that operate independently of phosphoribosylation."} {"id": "PMID:182680", "title": "Pulmonary angiotensin-converting enzyme. Interspecies homology and inhibition by heterologous antibody in vivo.", "content": "Goat antibody against pure rabbit pulmonary angiotensin-converting enzyme was used to probe homology of converting enzymes from other species. Immunologically cross-reactive material was found in detergent-solubilized extracts of lung particles from rat, guinea pig, and dog by double immunodiffusion, radioimmunoassay, and inhibition of enzyme activity. No homology was demonstrable with bovine, frog, or chicken lung extracts. Antibodies from different individual goats yielded comparable estimates of homology by immunodiffusion and radioimmunoassay. In contrast, they varied greatly in extent and specificity of their inhibitory action on heterologous enzyme activity. The vasopressor effect of angiotensin I and the vasodepressor effect of bradykinin were diminished and potentiated, respectively, in rats treated with anti-rabbit enzyme antibody. A smaller but significant immune-dependent inhibition of the vasopressor response to angiotensin II was also observed.", "contents": "Pulmonary angiotensin-converting enzyme. Interspecies homology and inhibition by heterologous antibody in vivo. Goat antibody against pure rabbit pulmonary angiotensin-converting enzyme was used to probe homology of converting enzymes from other species. Immunologically cross-reactive material was found in detergent-solubilized extracts of lung particles from rat, guinea pig, and dog by double immunodiffusion, radioimmunoassay, and inhibition of enzyme activity. No homology was demonstrable with bovine, frog, or chicken lung extracts. Antibodies from different individual goats yielded comparable estimates of homology by immunodiffusion and radioimmunoassay. In contrast, they varied greatly in extent and specificity of their inhibitory action on heterologous enzyme activity. The vasopressor effect of angiotensin I and the vasodepressor effect of bradykinin were diminished and potentiated, respectively, in rats treated with anti-rabbit enzyme antibody. A smaller but significant immune-dependent inhibition of the vasopressor response to angiotensin II was also observed."} {"id": "PMID:182681", "title": "Specific herpes simplex virus-induced incorporation of 5-iodo-5'-amino-2',5'-dideoxyuridine into deoxyribonucleic acid.", "content": "5-Iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd) is a novel thymidine analog which inhibits herpes simplex virus, type 1 (HS-1 virus) replication in the absence of detectable host toxicity. When murine, simian, or human cells in culture are treated with [125I]AIdUrd for up to 24 hours essentially none of the nucleoside becomes cell-associated. In contrast, upon HS-1 virus infection significant radiolabel is detected in both nucleotide pools and in DNA. The major acid-soluble metabolite has been shown by enzymic and chromatographic analysis to be the 5'-triphosphate of AIdUrd. DNA from HS-1 virus-infected Vero cells labeled with [14C]thymidine, 5-[125I]iodo-2'-deoxyuridine (IdUrd), or [125I]AIdUrd was isolated by buoyant density centrifugation and subjected to digestion by pancreatic DNase I, spleen DNase II, micrococcal nuclease, spleen, and venom phosphodiesterases. Analysis of the digestion products clearly indicate that AIdUrd is incorporated internally into the DNA structure. DNA containing AIdUrd therefore contains phosphoramidate (P-N) bonds, known to be extremely acid-labile. The selective HS-1 virus-induced phosphorylation of AIdUrd and its subsequent incorporation into DNA may account for the unique biological activity of the AIdUrd nucleoside.", "contents": "Specific herpes simplex virus-induced incorporation of 5-iodo-5'-amino-2',5'-dideoxyuridine into deoxyribonucleic acid. 5-Iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd) is a novel thymidine analog which inhibits herpes simplex virus, type 1 (HS-1 virus) replication in the absence of detectable host toxicity. When murine, simian, or human cells in culture are treated with [125I]AIdUrd for up to 24 hours essentially none of the nucleoside becomes cell-associated. In contrast, upon HS-1 virus infection significant radiolabel is detected in both nucleotide pools and in DNA. The major acid-soluble metabolite has been shown by enzymic and chromatographic analysis to be the 5'-triphosphate of AIdUrd. DNA from HS-1 virus-infected Vero cells labeled with [14C]thymidine, 5-[125I]iodo-2'-deoxyuridine (IdUrd), or [125I]AIdUrd was isolated by buoyant density centrifugation and subjected to digestion by pancreatic DNase I, spleen DNase II, micrococcal nuclease, spleen, and venom phosphodiesterases. Analysis of the digestion products clearly indicate that AIdUrd is incorporated internally into the DNA structure. DNA containing AIdUrd therefore contains phosphoramidate (P-N) bonds, known to be extremely acid-labile. The selective HS-1 virus-induced phosphorylation of AIdUrd and its subsequent incorporation into DNA may account for the unique biological activity of the AIdUrd nucleoside."} {"id": "PMID:182682", "title": "Structural polypeptides of mammalian type C RNA viruses. Isolation and immunologic characterization of a low molecular weight polypeptide, p10.", "content": "Low molecular weight polypeptides of several mammalian type C RNA tumor viruses were purified by sequential ion exchange chromatography and molecular sizing techniques. These included a polypeptide with a molecular weight of 10,000 to 11,000, p 10, from two type C viruses of mouse origin. Rauscher- and Moloney-murine leukemia virus (MuL virus), and from an infectious type C virus isolate of the woolly monkey. The p12 structural polypeptides of these viruses as well as Rauscher-MuL virus p15 were also purified. By using radioimmunoassays developed for each polypeptide, it was possible to demonstrate that all three low molecular weight polypeptides, p15, p12, and p10, were immunologically unique. Among type C viral structural polypeptides, p10 has been least well characterized immunologically. The results of the present study indicate that p10 is virus-coded and possesses strong group-specific antigenic determinants. By use of appropriate immunoassays, broadly reactive interspecies determinants shared by mammalian type C virus isolates of murine, feline, and primate origin, were also demonstrated. The interspecies antigenic determinants of p10 were shown to be as broadly cross-reactive as those exhibited by the major type C virus structural polypeptide, p30.", "contents": "Structural polypeptides of mammalian type C RNA viruses. Isolation and immunologic characterization of a low molecular weight polypeptide, p10. Low molecular weight polypeptides of several mammalian type C RNA tumor viruses were purified by sequential ion exchange chromatography and molecular sizing techniques. These included a polypeptide with a molecular weight of 10,000 to 11,000, p 10, from two type C viruses of mouse origin. Rauscher- and Moloney-murine leukemia virus (MuL virus), and from an infectious type C virus isolate of the woolly monkey. The p12 structural polypeptides of these viruses as well as Rauscher-MuL virus p15 were also purified. By using radioimmunoassays developed for each polypeptide, it was possible to demonstrate that all three low molecular weight polypeptides, p15, p12, and p10, were immunologically unique. Among type C viral structural polypeptides, p10 has been least well characterized immunologically. The results of the present study indicate that p10 is virus-coded and possesses strong group-specific antigenic determinants. By use of appropriate immunoassays, broadly reactive interspecies determinants shared by mammalian type C virus isolates of murine, feline, and primate origin, were also demonstrated. The interspecies antigenic determinants of p10 were shown to be as broadly cross-reactive as those exhibited by the major type C virus structural polypeptide, p30."} {"id": "PMID:182683", "title": "Microsomal membrane permeability and the hepatic glucose-6-phosphatase system. Interactions of the system with D-mannose 6-phosphate and D-mannose.", "content": "We have proposed that glucose-6-phosphatase (EC 3.1.3.9) is a two-component system consisting of (a) a glucose-6-P-specific transporter which mediates the movement of the hexose phosphate from the cytosol to the lumen of the endoplasmic reticulum (or cisternae of the isolated microsomal vesicle), and (b) a nonspecific phosphohydrolase-phosphotransferase localized on the luminal surface of the membrane (Arion, W.J., Wallin, B.K., Lange, A.J., and Ballas, L.M. (1975) Mol. Cell. Biochem. 6, 75-83). Additional support for this model has been obtained by studying the interactions of D-mannose-6-P and D-mannose with the enzyme of untreated (i.e. intact) and taurocholate-disrupted microsomes. An exact correspondence was shown between the mannose-6-P phosphohydrolase activity at low substrate concentrations and the permeability of the microsomal membrane to EDTA. The state of intactness of the membrane influenced the kinetics of mannose inhibition of glucose-6-P hydrolysis; uncompetitive and noncompetitive inhibitions were observed for intact and disrupted microsomes, respectively. The apparent Km for glucose-6-P was smaller with intact preparations at mannose concentrations above 0.3 M. Mannose significantly inhibited total glucose-6-P utilization by intact microsomes, whereas D-glucose had a stimulatory effect. Both hexoses markedly enhanced the rate of glucose-6-P utilization by disrupted microsomes. The actions of mannose on the glucose-6-phosphatase of intact microsomes fully support the postulated transport model. They are predictable consequences of the synthesis and accumulation of mannose-6-P in the cisternae of microsomal vesicles which possess a nonspecific, multifunctional enzyme on the inner surface and a limiting membrane permeable to D-glucose, D-mannose, glucose-6-P, but impermeable to mannose-6-P. The latency of the mannose-6-P phosphohydrolase activity is proposed as a reliable, quantitative index of microsomal membrane integrity. The inherent limitations of the use of EDTA permeability for this purpose are discussed.", "contents": "Microsomal membrane permeability and the hepatic glucose-6-phosphatase system. Interactions of the system with D-mannose 6-phosphate and D-mannose. We have proposed that glucose-6-phosphatase (EC 3.1.3.9) is a two-component system consisting of (a) a glucose-6-P-specific transporter which mediates the movement of the hexose phosphate from the cytosol to the lumen of the endoplasmic reticulum (or cisternae of the isolated microsomal vesicle), and (b) a nonspecific phosphohydrolase-phosphotransferase localized on the luminal surface of the membrane (Arion, W.J., Wallin, B.K., Lange, A.J., and Ballas, L.M. (1975) Mol. Cell. Biochem. 6, 75-83). Additional support for this model has been obtained by studying the interactions of D-mannose-6-P and D-mannose with the enzyme of untreated (i.e. intact) and taurocholate-disrupted microsomes. An exact correspondence was shown between the mannose-6-P phosphohydrolase activity at low substrate concentrations and the permeability of the microsomal membrane to EDTA. The state of intactness of the membrane influenced the kinetics of mannose inhibition of glucose-6-P hydrolysis; uncompetitive and noncompetitive inhibitions were observed for intact and disrupted microsomes, respectively. The apparent Km for glucose-6-P was smaller with intact preparations at mannose concentrations above 0.3 M. Mannose significantly inhibited total glucose-6-P utilization by intact microsomes, whereas D-glucose had a stimulatory effect. Both hexoses markedly enhanced the rate of glucose-6-P utilization by disrupted microsomes. The actions of mannose on the glucose-6-phosphatase of intact microsomes fully support the postulated transport model. They are predictable consequences of the synthesis and accumulation of mannose-6-P in the cisternae of microsomal vesicles which possess a nonspecific, multifunctional enzyme on the inner surface and a limiting membrane permeable to D-glucose, D-mannose, glucose-6-P, but impermeable to mannose-6-P. The latency of the mannose-6-P phosphohydrolase activity is proposed as a reliable, quantitative index of microsomal membrane integrity. The inherent limitations of the use of EDTA permeability for this purpose are discussed."} {"id": "PMID:182684", "title": "Rat high density lipoprotein subfraction (HDL3) uptake and catabolism by isolated rat liver parenchymal cells.", "content": "Rat liver parenchymal cell binding, uptake, and proteolytic degradation of rat 125I-labeled high density lipoprotein (HDL) subfraction, HDL3 (1.10 less than d less than 1.210 g/ml), in which apo-A-I is the major polypeptide, were investigated. Structural and metabolic integrity of the isolated cells was verified by trypan blue exclusion, low lactic dehydrogenase leakage, expected morphology, and gluconeogenesis from lactate and pyruvate. 125I-labeled HDL3 was incubated with 10 X 10(6) cells at 37 degrees and 4 degrees in albumin and Krebs-Henseleit bicarbonate buffer, pH 7.4. Binding and uptake were determined by radioactivity in washed cells. Proteolytic degradation was determined by trichloroacetic acid-soluble radioactivity in the incubation medium. At 37 degrees, maximum HDL3 binding (Bmax) and uptake occurred at 30 min with a Bmax of 31 ng/mg dry weight of cells. The apparent dissociation constant of the HDL3 receptor system (Kd) was 60 X 10(-8) M, based on Mr = 28,000 of apo-A-I, the predominant rat HDL3 protein. Proteolytic degradation showed a 15-min lag and then constant proteolysis. After 2 hours 5.8% of incubated 125I-labeled HDL3 was degraded. Sixty per cent of cell radioactivity at 37 degrees was trypsin-releasable. At 37 degrees, 125I-labeled HDL3 was incubated with cells in the presence of varying concentrations of native (cold) HDL3, very low density lipoproteins, and low density lipoproteins. Incubation with native HDL3 resulted in greatest inhibition of 125I-labeled HDL3 binding, uptake, and proteolytic degradation. When 125I-labeled HDL3 was preincubated with increasing amounts of HDL3 antiserum, binding and uptake by cells were decreased to complete inhibition. Cell binding, uptake, and proteolytic degradation of 125I-labeled HDL3 were markedly diminished at 4 degrees. Less than 1 mM chloroquine enhanced 125I-labeled HDL3 proteolysis but at 5 mM or greater, chloroquine inhibited proteolysis with 125I-labeled HDL3 accumulation in cells. L-[U-14C]Lysine-labeled HDL3 was bound, taken up, and degraded by cells as effectively as 125I-labeled HDL3. These data suggest that liver cell binding, uptake, and proteolytic degradation of rat HDL3 are actively performed and linked in the sequence:binding, then uptake, and finally proteolytic degradation. Furthermore, there may be a specific HDL3 (lipoprotein A) receptor of recognition site(s) on the plasma membrane. Finally, our data further support our previous reports of the important role of liver lysosomes in proteolytic degradation of HDL3.", "contents": "Rat high density lipoprotein subfraction (HDL3) uptake and catabolism by isolated rat liver parenchymal cells. Rat liver parenchymal cell binding, uptake, and proteolytic degradation of rat 125I-labeled high density lipoprotein (HDL) subfraction, HDL3 (1.10 less than d less than 1.210 g/ml), in which apo-A-I is the major polypeptide, were investigated. Structural and metabolic integrity of the isolated cells was verified by trypan blue exclusion, low lactic dehydrogenase leakage, expected morphology, and gluconeogenesis from lactate and pyruvate. 125I-labeled HDL3 was incubated with 10 X 10(6) cells at 37 degrees and 4 degrees in albumin and Krebs-Henseleit bicarbonate buffer, pH 7.4. Binding and uptake were determined by radioactivity in washed cells. Proteolytic degradation was determined by trichloroacetic acid-soluble radioactivity in the incubation medium. At 37 degrees, maximum HDL3 binding (Bmax) and uptake occurred at 30 min with a Bmax of 31 ng/mg dry weight of cells. The apparent dissociation constant of the HDL3 receptor system (Kd) was 60 X 10(-8) M, based on Mr = 28,000 of apo-A-I, the predominant rat HDL3 protein. Proteolytic degradation showed a 15-min lag and then constant proteolysis. After 2 hours 5.8% of incubated 125I-labeled HDL3 was degraded. Sixty per cent of cell radioactivity at 37 degrees was trypsin-releasable. At 37 degrees, 125I-labeled HDL3 was incubated with cells in the presence of varying concentrations of native (cold) HDL3, very low density lipoproteins, and low density lipoproteins. Incubation with native HDL3 resulted in greatest inhibition of 125I-labeled HDL3 binding, uptake, and proteolytic degradation. When 125I-labeled HDL3 was preincubated with increasing amounts of HDL3 antiserum, binding and uptake by cells were decreased to complete inhibition. Cell binding, uptake, and proteolytic degradation of 125I-labeled HDL3 were markedly diminished at 4 degrees. Less than 1 mM chloroquine enhanced 125I-labeled HDL3 proteolysis but at 5 mM or greater, chloroquine inhibited proteolysis with 125I-labeled HDL3 accumulation in cells. L-[U-14C]Lysine-labeled HDL3 was bound, taken up, and degraded by cells as effectively as 125I-labeled HDL3. These data suggest that liver cell binding, uptake, and proteolytic degradation of rat HDL3 are actively performed and linked in the sequence:binding, then uptake, and finally proteolytic degradation. Furthermore, there may be a specific HDL3 (lipoprotein A) receptor of recognition site(s) on the plasma membrane. Finally, our data further support our previous reports of the important role of liver lysosomes in proteolytic degradation of HDL3."} {"id": "PMID:182685", "title": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase. Distinct forms in human lymphocytes and monocytes.", "content": "Adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase activity of normal human peripheral blood leukocyte suspensions containing 90% lymphocytes and 10% monocytes showed anomalous kinetic behavior indicative of multiple enzyme forms. Kinetic analyses of purified lymphocyte (99%) or monocyte preparations (95%) indicated that only one type of phosphodiesterase was present in each cell type. None of the preparations contained any detectable guanosine 3':5'-monophosphate (cyclic GMP) hydrolytic activity. The lymphocyte enzyme had an apparent Km congruent to 0.4 muM for cyclic AMP and Vmax congruent to 0.5 picomoles/min/10(6) cells. These kinetic parameters were confirmed by several cell purification techniques used alone and sequentially. Sedimentation velocity analyses indicated that the higher Km monocyte enzyme had a molecular weight near 45,000 and that the lower Km lymphocyte enzyme most likely had a molecular weight near 98,000. A variety of procedures led to a loss of the higher molecular weight, high affinity enzyme leaving only the enzyme of 45,000 daltons with a much lower substrate affinity. A long term, stable human lymphoblastoid cell line had cyclic AMP phosphodiesterase activity that was similar to the lymphocyte enzyme by both physical and kinetic criteria. Lymphocyte cyclic AMP phosphodiesterase appears to be a soluble enzyme whose pH and temperature optima and cationic requirements are similar to those of other mammalian phosphodiesterases. The distinct cyclic AMP phosphodiesterase forms of these cells may possibly represent the basic, active subunit of mammalian cyclic nucleotide phosphodiesterases. We hypothesize that the extremely high affinity cyclic AMP phosphodiesterase of normal lymphocytes plays an important role in the regulation of normal function in these cells, and also in the rapid proliferative responses characteristic of the stimulated lymphocyte.", "contents": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase. Distinct forms in human lymphocytes and monocytes. Adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase activity of normal human peripheral blood leukocyte suspensions containing 90% lymphocytes and 10% monocytes showed anomalous kinetic behavior indicative of multiple enzyme forms. Kinetic analyses of purified lymphocyte (99%) or monocyte preparations (95%) indicated that only one type of phosphodiesterase was present in each cell type. None of the preparations contained any detectable guanosine 3':5'-monophosphate (cyclic GMP) hydrolytic activity. The lymphocyte enzyme had an apparent Km congruent to 0.4 muM for cyclic AMP and Vmax congruent to 0.5 picomoles/min/10(6) cells. These kinetic parameters were confirmed by several cell purification techniques used alone and sequentially. Sedimentation velocity analyses indicated that the higher Km monocyte enzyme had a molecular weight near 45,000 and that the lower Km lymphocyte enzyme most likely had a molecular weight near 98,000. A variety of procedures led to a loss of the higher molecular weight, high affinity enzyme leaving only the enzyme of 45,000 daltons with a much lower substrate affinity. A long term, stable human lymphoblastoid cell line had cyclic AMP phosphodiesterase activity that was similar to the lymphocyte enzyme by both physical and kinetic criteria. Lymphocyte cyclic AMP phosphodiesterase appears to be a soluble enzyme whose pH and temperature optima and cationic requirements are similar to those of other mammalian phosphodiesterases. The distinct cyclic AMP phosphodiesterase forms of these cells may possibly represent the basic, active subunit of mammalian cyclic nucleotide phosphodiesterases. We hypothesize that the extremely high affinity cyclic AMP phosphodiesterase of normal lymphocytes plays an important role in the regulation of normal function in these cells, and also in the rapid proliferative responses characteristic of the stimulated lymphocyte."} {"id": "PMID:182686", "title": "Preparation and characterization of hormone-sensitive, resealed erythrocyte ghosts.", "content": "A method for preparing resealed turkey erythrocyte ghosts is described which utilizes hypotonic lysis and resealing following restoration of isotonicity. The resealed ghosts are isolated above 55% sucrose. The resealed ghosts are shown to be capable of maintaining high intracellular K+ concentrations in the presence of a low K+ extracellular environment. When ATP and an ATP-regenerating system are included during the resealing stage, (R)-(-)-epinephrine- and NaF-stimulated cyclic AMP accumulation, which is linear for 20 min, can be demonstrated. The concentration of (R)-(-)-epinephrine producing a half-maximal response in resealed ghosts is 1.0 +/- 0.4 X 10(-6) M. This is the same as that for (R)-(-)-epinephrine in the intact erythrocyte. The resealed ghosts are impermeable to Ca2+, but Ca2+ inhibition of cyclic AMP accumulation is noted if the divalent cation ionophore. A-23187, is present or if Ca2+ is included during the resealing stage.", "contents": "Preparation and characterization of hormone-sensitive, resealed erythrocyte ghosts. A method for preparing resealed turkey erythrocyte ghosts is described which utilizes hypotonic lysis and resealing following restoration of isotonicity. The resealed ghosts are isolated above 55% sucrose. The resealed ghosts are shown to be capable of maintaining high intracellular K+ concentrations in the presence of a low K+ extracellular environment. When ATP and an ATP-regenerating system are included during the resealing stage, (R)-(-)-epinephrine- and NaF-stimulated cyclic AMP accumulation, which is linear for 20 min, can be demonstrated. The concentration of (R)-(-)-epinephrine producing a half-maximal response in resealed ghosts is 1.0 +/- 0.4 X 10(-6) M. This is the same as that for (R)-(-)-epinephrine in the intact erythrocyte. The resealed ghosts are impermeable to Ca2+, but Ca2+ inhibition of cyclic AMP accumulation is noted if the divalent cation ionophore. A-23187, is present or if Ca2+ is included during the resealing stage."} {"id": "PMID:182687", "title": "Gonadotropin binding factor(s). Extraction of high affinity gonadotropin binding sites from rat testis and partial characterization of their interaction with human follitropin, lutropin, and choriogonadotropin.", "content": "Factor(s) that bind gonadotropins have been extracted from rat testis by 30% ethanol (v/v) in water and their interaction with human lutropin (hLH) and human follitropin (hFSH) have been investigated by a new assay using dextran-coated charcoal. These studies reveal that: 1. Maximal binding of gonadotropin with soluble factors was observed over a broad range of pH from 6.0 to 8.0 with a relative decline in binding at extremes of pH. The binding was independent of the ionic strength of the buffer and reached equilibrium within 5 min at 4 degrees, 27 degrees, and 37 degrees. 2. The soluble factors have marked thermostability, a point of distinction from detergent-solubilized receptors. 3. The equilibrium dissociation constant (Kd) of 125I-hFSH binding to the soluble factor was 6.0 +/- 0.58 X 10(-10) M, consistent with the values obtained from the membrane binding studies. Similarly, the Kd value for 125I-hLH to the soluble factor(s) was 3.33 +/- 0.3 X 10(-9) M, comparable to the values obtained from the membrane binding studies. Hill plots demonstrated a lack of a cooperative relationship with an apparent Hill coefficient of 1.071 for hLH and 0.909 for hFSH. Furthermore, two classes of binding sites for 125I-human choriogonadotropin (hCG) were clearly discernible by both Lineweaver-Burk and Hill plots with an equilibrium dissociation constant of 2.4 +/- 0.5 X 10(-11) M and 1.35 +/- 1.2 X 10(-9) M. The apparent Hill coefficient of interaction of 125I-hCG with the soluble factors was found to be 0.923 for high affinity and 1.09 for low affinity binding sites. 4. The binding of 125I-hLH and 125I-hFSH with respect to concentrations of soluble factor(s) was found to be a saturable process, yielding an expected 4.4-fold higher Kd for hLH (294 +/- 13.8 mug/ml) compared to hFSH (66.6 +/- 4 mug/ml). These findings are comparable with the equilibrium dissociation constants, thus confirming a 5-fold higher affinity of hFSH as compared to hLH for the soluble factors, i.e. the ratio of 3.0 X 10(-9) M to 6.0 X 10(-10) M versus the ratio of 294 mug/ml to 66.6 mug/ml. 5. The hormone specificity of the interaction has been studied by using radiolabeled hFSH, hLH, hCG, prolactin, growth hormone, and bovine serum albumin. The binding of FSH at low factor concentrations was found to be 5- to 10-fold greater than prolactin, growth hormone, and albumin. 6. The soluble factors are found in higher concentration in testis compared to liver, kidney, and blood. 7. The effect of ethanol upon solubilization of the factor(s) has been investigated. The factor(s) can be extracted with buffer or water alone. However, 10 to 25% of ethanol (v/v) facilitates the process of solubilization. The treatment with 70% ethanol (v/v) or more did not extract any factor activity from testes. The factor(s) were insoluble in petroleum ether, chloroform, absolute ethanol, methanol, or lipid solvent. 8. Finally the effect of soluble factors on classical membrane binding was investigated...", "contents": "Gonadotropin binding factor(s). Extraction of high affinity gonadotropin binding sites from rat testis and partial characterization of their interaction with human follitropin, lutropin, and choriogonadotropin. Factor(s) that bind gonadotropins have been extracted from rat testis by 30% ethanol (v/v) in water and their interaction with human lutropin (hLH) and human follitropin (hFSH) have been investigated by a new assay using dextran-coated charcoal. These studies reveal that: 1. Maximal binding of gonadotropin with soluble factors was observed over a broad range of pH from 6.0 to 8.0 with a relative decline in binding at extremes of pH. The binding was independent of the ionic strength of the buffer and reached equilibrium within 5 min at 4 degrees, 27 degrees, and 37 degrees. 2. The soluble factors have marked thermostability, a point of distinction from detergent-solubilized receptors. 3. The equilibrium dissociation constant (Kd) of 125I-hFSH binding to the soluble factor was 6.0 +/- 0.58 X 10(-10) M, consistent with the values obtained from the membrane binding studies. Similarly, the Kd value for 125I-hLH to the soluble factor(s) was 3.33 +/- 0.3 X 10(-9) M, comparable to the values obtained from the membrane binding studies. Hill plots demonstrated a lack of a cooperative relationship with an apparent Hill coefficient of 1.071 for hLH and 0.909 for hFSH. Furthermore, two classes of binding sites for 125I-human choriogonadotropin (hCG) were clearly discernible by both Lineweaver-Burk and Hill plots with an equilibrium dissociation constant of 2.4 +/- 0.5 X 10(-11) M and 1.35 +/- 1.2 X 10(-9) M. The apparent Hill coefficient of interaction of 125I-hCG with the soluble factors was found to be 0.923 for high affinity and 1.09 for low affinity binding sites. 4. The binding of 125I-hLH and 125I-hFSH with respect to concentrations of soluble factor(s) was found to be a saturable process, yielding an expected 4.4-fold higher Kd for hLH (294 +/- 13.8 mug/ml) compared to hFSH (66.6 +/- 4 mug/ml). These findings are comparable with the equilibrium dissociation constants, thus confirming a 5-fold higher affinity of hFSH as compared to hLH for the soluble factors, i.e. the ratio of 3.0 X 10(-9) M to 6.0 X 10(-10) M versus the ratio of 294 mug/ml to 66.6 mug/ml. 5. The hormone specificity of the interaction has been studied by using radiolabeled hFSH, hLH, hCG, prolactin, growth hormone, and bovine serum albumin. The binding of FSH at low factor concentrations was found to be 5- to 10-fold greater than prolactin, growth hormone, and albumin. 6. The soluble factors are found in higher concentration in testis compared to liver, kidney, and blood. 7. The effect of ethanol upon solubilization of the factor(s) has been investigated. The factor(s) can be extracted with buffer or water alone. However, 10 to 25% of ethanol (v/v) facilitates the process of solubilization. The treatment with 70% ethanol (v/v) or more did not extract any factor activity from testes. The factor(s) were insoluble in petroleum ether, chloroform, absolute ethanol, methanol, or lipid solvent. 8. Finally the effect of soluble factors on classical membrane binding was investigated..."} {"id": "PMID:182688", "title": "Metabolism and excretion of exogenous adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate. Studies in the isolated perfused rat kidney and in the intact rat.", "content": "Isolated rat kidneys were perfused with a recirculating medium containing exogenous adenosine 3':5'-monophosphate (cyclic AMP) or guanosine 3':5'-monophosphate (cyclic GMP) at an initial concentration of 0.1 mM. Both cyclic nucleotides were rapidly removed from the perfusate. Urinary excretion accounted for about 20% and 40% of the respective cyclic AMP and cyclic GMP lost from the perfusate. The metabolism of the cyclic nucleotides was studied by 14C-labeled cyclic nucleotides in the perfusate. During 60 min, 30% of added cyclic [14C]AMP was metabolized to renal [14C]adenine nucleotides (ATP, ADP, and AMP) and 30% to perfusate [14C]uric acid. Similarly, 20% of cyclic[14C]GMP was metabolized to renal [14C]guanine nucleotides (GTP, GDP, and GMP) and 30% to perfusate [14C]uric acid. Urine contained principally unchanged 14C-labeled cyclic nucleotide. Addition of 0.1 mM cyclic AMP to the perfusate elevated the renal ATP and ADP contents 2-fold. Addition of 0.1 mM of either cyclic AMP or cyclic GMP to the perfusate also elevated the renal production of uric acid 2- to 3-fold. The production and distribution of metabolites of exogenous cyclic nucleotides were also studied in the intact rat. Within 60 min after injection, 3.3 mumol of either 14C-labeled cyclic AMP or cyclic GMP was cleared from the plasma. Kidney cortex and liver were the principal tissues for 14C accumulation. Urinary excretion accounted for about 20 and 45% of the cyclic [14C]AMP and cyclic [14C]GMP lost from the plasma, respectively. The 14C found in the kidney and liver was present almost entirely as the respective purine mono-, di-, and trinucleotides. The other principal metabolite was [14C]allantoin, found in the urine and, to a lesser extent, the liver. The urine contained mostly unchanged 14C-labeled cyclic nucleotide. Unlike the findings with the perfused kidney, [14C]uric acid was not a significant metabolite of the 14C-labeled cyclic nucleotides in these in vivo experiments.", "contents": "Metabolism and excretion of exogenous adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate. Studies in the isolated perfused rat kidney and in the intact rat. Isolated rat kidneys were perfused with a recirculating medium containing exogenous adenosine 3':5'-monophosphate (cyclic AMP) or guanosine 3':5'-monophosphate (cyclic GMP) at an initial concentration of 0.1 mM. Both cyclic nucleotides were rapidly removed from the perfusate. Urinary excretion accounted for about 20% and 40% of the respective cyclic AMP and cyclic GMP lost from the perfusate. The metabolism of the cyclic nucleotides was studied by 14C-labeled cyclic nucleotides in the perfusate. During 60 min, 30% of added cyclic [14C]AMP was metabolized to renal [14C]adenine nucleotides (ATP, ADP, and AMP) and 30% to perfusate [14C]uric acid. Similarly, 20% of cyclic[14C]GMP was metabolized to renal [14C]guanine nucleotides (GTP, GDP, and GMP) and 30% to perfusate [14C]uric acid. Urine contained principally unchanged 14C-labeled cyclic nucleotide. Addition of 0.1 mM cyclic AMP to the perfusate elevated the renal ATP and ADP contents 2-fold. Addition of 0.1 mM of either cyclic AMP or cyclic GMP to the perfusate also elevated the renal production of uric acid 2- to 3-fold. The production and distribution of metabolites of exogenous cyclic nucleotides were also studied in the intact rat. Within 60 min after injection, 3.3 mumol of either 14C-labeled cyclic AMP or cyclic GMP was cleared from the plasma. Kidney cortex and liver were the principal tissues for 14C accumulation. Urinary excretion accounted for about 20 and 45% of the cyclic [14C]AMP and cyclic [14C]GMP lost from the plasma, respectively. The 14C found in the kidney and liver was present almost entirely as the respective purine mono-, di-, and trinucleotides. The other principal metabolite was [14C]allantoin, found in the urine and, to a lesser extent, the liver. The urine contained mostly unchanged 14C-labeled cyclic nucleotide. Unlike the findings with the perfused kidney, [14C]uric acid was not a significant metabolite of the 14C-labeled cyclic nucleotides in these in vivo experiments."} {"id": "PMID:182689", "title": "Purification and characterization of the carrier protein for juvenile hormone from the hemolymph of the tobacco hornworm Manduca sexta Johannson (Lepidoptera: Sphingidae).", "content": "The larval hemolymph of the tobacco hornworm, Manduca sexta, contains a carrier protein that binds specifically and with high affinity the juvenile hormone, an important regulator of insect development. This protein serves to transport the hormone and to protect it from the action of degradative enzymes during early larval stages. Using hemolymph from the last larval stage, we have isolated a pure carrier protein using acetone precipitation, gel filtration, ion exchange chromatography, and preparative isoelectric focusing. Gel filtration, polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and equilibrium ultracentrifugation established that the carrier protein is a single chain polypeptide of approximately 28,000 daltons. The amino acid composition is unexceptional, and no evidence for hexosamine has been obtained. An ion exchange filter disc assay method was used to determine the formation of the complex between the carrier protein and isotopically labeled juvenile hormone. With this technique it was shown that each carrier protein binds one hormone molecule with a dissociation constant of 4.4 +/- 0.2 X 10(-7) M at 0 degrees.", "contents": "Purification and characterization of the carrier protein for juvenile hormone from the hemolymph of the tobacco hornworm Manduca sexta Johannson (Lepidoptera: Sphingidae). The larval hemolymph of the tobacco hornworm, Manduca sexta, contains a carrier protein that binds specifically and with high affinity the juvenile hormone, an important regulator of insect development. This protein serves to transport the hormone and to protect it from the action of degradative enzymes during early larval stages. Using hemolymph from the last larval stage, we have isolated a pure carrier protein using acetone precipitation, gel filtration, ion exchange chromatography, and preparative isoelectric focusing. Gel filtration, polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and equilibrium ultracentrifugation established that the carrier protein is a single chain polypeptide of approximately 28,000 daltons. The amino acid composition is unexceptional, and no evidence for hexosamine has been obtained. An ion exchange filter disc assay method was used to determine the formation of the complex between the carrier protein and isotopically labeled juvenile hormone. With this technique it was shown that each carrier protein binds one hormone molecule with a dissociation constant of 4.4 +/- 0.2 X 10(-7) M at 0 degrees."} {"id": "PMID:182690", "title": "Incorporation of D-[3-3H, U-14C] glucose into glycerolipid via acyl dihydroxyacetone phosphate untransformed and viral-transformed BHK-21-c13 fibroblasts.", "content": "Untransformed BHK-21-c13 fibroblasts as well as 4 polyoma-transformed strains were incubated with D-[U-14C,3-3H]glucose. This substrate generates intracellular labeled glycerol, and also [4-3H]NADPH via the phosphogluconate oxidative pathway. The latter selectively transfers hydrogen to C-2 of glycerol in glycerolipid via the acyl dihydroxyacetone phosphate pathway. After incubation, the distribution of radioactivity and the ratios of 3H/14C at the three positions of recovered glycerol were determined in sn-glycerol 3-phosphate, saponifiable glycerolipids, alkyl ether glycerolipids, and plasmalogens. In each of the cell types examined, 3H in the sn-1 position of glycerol in the recovered ether-containing glycerolipids was negligible, yet this position contained most of the recovered 3H in sn-glycerol 3-phosphate and saponifiable glycerolipids. The 3H/14C ratio in position 2 of glycerol, measured at various incubation times, was from 5- to 200-fold greater in the saponifiable glycerolipids than in free sn-glycerol 3-phosphate. The ratio in position 2 of ether-containing glycerolipids was the same or greater than that in the saponifiable glycerolipids in all of the cell types employed. A similar pattern in the 3H/14C ratio was observed when BHK-21-c13 cells were incubated with D-[U-14C,1-3H]glucose. These observations demonstrate significant participation of the acyl dihydroxyacetone phosphate pathway in glycerolipid synthesis in BHK cells.", "contents": "Incorporation of D-[3-3H, U-14C] glucose into glycerolipid via acyl dihydroxyacetone phosphate untransformed and viral-transformed BHK-21-c13 fibroblasts. Untransformed BHK-21-c13 fibroblasts as well as 4 polyoma-transformed strains were incubated with D-[U-14C,3-3H]glucose. This substrate generates intracellular labeled glycerol, and also [4-3H]NADPH via the phosphogluconate oxidative pathway. The latter selectively transfers hydrogen to C-2 of glycerol in glycerolipid via the acyl dihydroxyacetone phosphate pathway. After incubation, the distribution of radioactivity and the ratios of 3H/14C at the three positions of recovered glycerol were determined in sn-glycerol 3-phosphate, saponifiable glycerolipids, alkyl ether glycerolipids, and plasmalogens. In each of the cell types examined, 3H in the sn-1 position of glycerol in the recovered ether-containing glycerolipids was negligible, yet this position contained most of the recovered 3H in sn-glycerol 3-phosphate and saponifiable glycerolipids. The 3H/14C ratio in position 2 of glycerol, measured at various incubation times, was from 5- to 200-fold greater in the saponifiable glycerolipids than in free sn-glycerol 3-phosphate. The ratio in position 2 of ether-containing glycerolipids was the same or greater than that in the saponifiable glycerolipids in all of the cell types employed. A similar pattern in the 3H/14C ratio was observed when BHK-21-c13 cells were incubated with D-[U-14C,1-3H]glucose. These observations demonstrate significant participation of the acyl dihydroxyacetone phosphate pathway in glycerolipid synthesis in BHK cells."} {"id": "PMID:182691", "title": "Progesterone-binding components of chick oviduct. In vitro effects of purified hormone-receptor complexes on the initiation of RNA synthesis in chromatin.", "content": "We have investigated the manner by which progesterone receptors act to induce initiation of RNA synthesis in a cell-free system derived from chick oviduct. A method utilizing rifampicin enabled us to measure the formation of binary initiation complexes between RNA polymerase and chick oviduct chromatin (Tsai, M.-J., Schwartz, R.J., Tsai S.Y., and O'Malley, B.W. (1975) J.Biol. Chem. 250, 5165-5174) and allowed for the quantitative assessment of RNA chain initiation sites, RNA chain propagation rates, and RNA chain size under conditions which prevent secondary chain reinitiations. We have measured the available initiation sites for transcription in oviduct chromatin prepared from chicks withdrawn from all hormone and then restimulated with a secondary injection of progesterone. Within 1/2 hour after administration of progesterone, the number of initiation sites increased from 8,700 sites/pg of chromatin DNA for the control to 15,500 sites. After 1 hour, the concentration of RNA polymerase needed to saturate chromatin binding sites was increased 60% in comparison to control values, while the number of initiation sites increased 160%. This rapid increment in transcriptional activity preceded temporally the induction of synthesis of ovalbumin mRNA. To test directly the effect of progesterone receptor on transcription, in vitro, a reconstituted cell-free system was employed which contained purified cytoplasmic progesterone-receptor complexes, Escherichia coli RNA polymerase, and chromatin prepared from hormonally withdrawn chick oviducts. Purified progesterone-receptor complex stimulated transcription of oviduct chromatin in vitro by promoting an increase of 3,000 to 5,000 additional sites for RNA chain initiation. These data showed that progesterone receptor can directly increase the number of RNA polymerase binding and initiation sites in the chromatin template in the absence of a detectable change in either the rate of RNA chain propagation or the size of the RNA product. The kinetics of progesterone-receptor stimulation of RNA synthesis in chromatin revealed a t1/2 of 15 min for this effect to occur. This value was identical with the optimal time required for binding of receptor to chromatin. The concentration of receptor required for half-maximal stimulation of RNA chain initiation was approximately 5 x 10(-9) M. This value agreed closely with our previously reported estimates of the affinity (Kd approximately 5 x 10(-9)M) of the progesterone-receptor complex for oviduct chromatin. The stimulatory effect of purified progesterone receptor appeared to be relatively specific for oviduct chromatin in comparison to nontarget tissue chromatins or chick DNA. The data presented here show that steroid hormone-receptor complex can directly regulate gene transcription in vitro in a manner which mimics the events observed in vivo in target cells.", "contents": "Progesterone-binding components of chick oviduct. In vitro effects of purified hormone-receptor complexes on the initiation of RNA synthesis in chromatin. We have investigated the manner by which progesterone receptors act to induce initiation of RNA synthesis in a cell-free system derived from chick oviduct. A method utilizing rifampicin enabled us to measure the formation of binary initiation complexes between RNA polymerase and chick oviduct chromatin (Tsai, M.-J., Schwartz, R.J., Tsai S.Y., and O'Malley, B.W. (1975) J.Biol. Chem. 250, 5165-5174) and allowed for the quantitative assessment of RNA chain initiation sites, RNA chain propagation rates, and RNA chain size under conditions which prevent secondary chain reinitiations. We have measured the available initiation sites for transcription in oviduct chromatin prepared from chicks withdrawn from all hormone and then restimulated with a secondary injection of progesterone. Within 1/2 hour after administration of progesterone, the number of initiation sites increased from 8,700 sites/pg of chromatin DNA for the control to 15,500 sites. After 1 hour, the concentration of RNA polymerase needed to saturate chromatin binding sites was increased 60% in comparison to control values, while the number of initiation sites increased 160%. This rapid increment in transcriptional activity preceded temporally the induction of synthesis of ovalbumin mRNA. To test directly the effect of progesterone receptor on transcription, in vitro, a reconstituted cell-free system was employed which contained purified cytoplasmic progesterone-receptor complexes, Escherichia coli RNA polymerase, and chromatin prepared from hormonally withdrawn chick oviducts. Purified progesterone-receptor complex stimulated transcription of oviduct chromatin in vitro by promoting an increase of 3,000 to 5,000 additional sites for RNA chain initiation. These data showed that progesterone receptor can directly increase the number of RNA polymerase binding and initiation sites in the chromatin template in the absence of a detectable change in either the rate of RNA chain propagation or the size of the RNA product. The kinetics of progesterone-receptor stimulation of RNA synthesis in chromatin revealed a t1/2 of 15 min for this effect to occur. This value was identical with the optimal time required for binding of receptor to chromatin. The concentration of receptor required for half-maximal stimulation of RNA chain initiation was approximately 5 x 10(-9) M. This value agreed closely with our previously reported estimates of the affinity (Kd approximately 5 x 10(-9)M) of the progesterone-receptor complex for oviduct chromatin. The stimulatory effect of purified progesterone receptor appeared to be relatively specific for oviduct chromatin in comparison to nontarget tissue chromatins or chick DNA. The data presented here show that steroid hormone-receptor complex can directly regulate gene transcription in vitro in a manner which mimics the events observed in vivo in target cells."} {"id": "PMID:182692", "title": "Progesterone-binding components of chick oviduct. In vitro effect of receptor subunits on gene transcription.", "content": "We have studied chick oviduct progesterone receptor subunits and their effect on RNA transcription in oviduct chromatin. Initiation of RNA chain synthesis was measured by the rifampicin-challenge assay. Progesterone receptor subunits A and B were purified 200-fold by sequential chromatography on phosphocellulose, DEAE-cellulose, and hydroxylapatite. The subunits could be recombined to form the 6S receptor A-B dimer initially present in chick oviduct homogenates. The intact 6 S receptor dimer preparation increased transcription of oviduct chromatin by 40 to 60%. This increase corresponds to the creation of 5,800 new initiation sites per haploid cellular equivalent of DNA as chromatin. The increased chromatin transcription which resulted was half-maximal at a receptor concentration of about 5 x 10(-9) M. Preparations from other tissues which were devoid of progesterone-binding activity or oviduct preparations lacking progesterone did not stimulate rifampicin-resistant RNA synthesis. The oviduct receptor fraction contained no detectable glucocorticoid, androgen, or estrogen receptors. When isolated B subunits alone were incubated with chromatin, no transcriptional increase was detectable. Isolated A subunits increased chromatin transcription, but only at concentration approximately 10-fold higher than required of intact dimer. These observations suggest that the 6 S receptor dimer is the functional species in chromatin transcription in vivo; two hormones are required per dimer, one on each subunit. Since subunit A binds DNA and has stimulatory activity , a dimer dissociation at acceptor sites is postulated, liberating A subunits which stimulate RNA chain initiation sites.", "contents": "Progesterone-binding components of chick oviduct. In vitro effect of receptor subunits on gene transcription. We have studied chick oviduct progesterone receptor subunits and their effect on RNA transcription in oviduct chromatin. Initiation of RNA chain synthesis was measured by the rifampicin-challenge assay. Progesterone receptor subunits A and B were purified 200-fold by sequential chromatography on phosphocellulose, DEAE-cellulose, and hydroxylapatite. The subunits could be recombined to form the 6S receptor A-B dimer initially present in chick oviduct homogenates. The intact 6 S receptor dimer preparation increased transcription of oviduct chromatin by 40 to 60%. This increase corresponds to the creation of 5,800 new initiation sites per haploid cellular equivalent of DNA as chromatin. The increased chromatin transcription which resulted was half-maximal at a receptor concentration of about 5 x 10(-9) M. Preparations from other tissues which were devoid of progesterone-binding activity or oviduct preparations lacking progesterone did not stimulate rifampicin-resistant RNA synthesis. The oviduct receptor fraction contained no detectable glucocorticoid, androgen, or estrogen receptors. When isolated B subunits alone were incubated with chromatin, no transcriptional increase was detectable. Isolated A subunits increased chromatin transcription, but only at concentration approximately 10-fold higher than required of intact dimer. These observations suggest that the 6 S receptor dimer is the functional species in chromatin transcription in vivo; two hormones are required per dimer, one on each subunit. Since subunit A binds DNA and has stimulatory activity , a dimer dissociation at acceptor sites is postulated, liberating A subunits which stimulate RNA chain initiation sites."} {"id": "PMID:182693", "title": "Human plasma lipoproteins as accelerators of prothrombin activation.", "content": "The activation rate of bovine prothrombin by Factor Xa and Ca2+ has long been known to be greatly enhanced by addition of phospholipid. Upon substitution of human plasma lipoproteins for phospholipid (cephalin) in this activation system, only very low density lipoprotein enhances prothrombin activation. Low density lipoprotein and high density lipoprotein have no stimulatory effect on prothrombin activation. On the other hand, the sonicated lipid extracts from very low, low, and high density lipoproteins all can substitute for phospholipid in potentiating prothrombin activation. The efficiency of each lipid extract, in this regard, depends upon its source of extraction, and is greatest for the lipid extract of very low density lipoprotein.", "contents": "Human plasma lipoproteins as accelerators of prothrombin activation. The activation rate of bovine prothrombin by Factor Xa and Ca2+ has long been known to be greatly enhanced by addition of phospholipid. Upon substitution of human plasma lipoproteins for phospholipid (cephalin) in this activation system, only very low density lipoprotein enhances prothrombin activation. Low density lipoprotein and high density lipoprotein have no stimulatory effect on prothrombin activation. On the other hand, the sonicated lipid extracts from very low, low, and high density lipoproteins all can substitute for phospholipid in potentiating prothrombin activation. The efficiency of each lipid extract, in this regard, depends upon its source of extraction, and is greatest for the lipid extract of very low density lipoprotein."} {"id": "PMID:182694", "title": "Corticosteroid-binding proteins in human colostrum and milk and rat milk.", "content": "A corticosteroid-binding protein was detected in the whey of human colostrum and milk which resembles serum corticosteroid-binding globulin in certain respects: the equilibrium association constants for cortisol and progesterone binding and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar, and cortisol andd progesterone competed strongly for binding to the same site in each instance. Dexamethasone-binding activity could not be detected. The concentration of corticosteroid-binding protein in the colostrum obtained before parturition is about 0.1 muM; the concentration declines rapidly after parturition to about 0.01 muM. A corticosteroid-binding protein was found, also, in the whey of mature rat milk at levels of about 0.3 muM. This protein resembles rat serum corticosteroid-binding globulin: the equilibrium association constants for cortisol, corticosterone, and progesterone binding, and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar; the elution behavior of the respective proteins on anion exchange chromatography with DEAE-Sephadex A-50 was similar, also. Identity of the corticosteroid-binding proteins in whey with corticosteroid-binding globulin in serum is not presumed, however. Rat and human whey exhibited very little testosterone- or 17 beta-estradiol-binding activity. It is suggested the corticosteroid-binding proteins may play a significant physiological role in regulating the concentration of the bound and unbound forms of progesterone and cortisol in the fluids bathing the epithelial cells lining the mammary ducts and acini.", "contents": "Corticosteroid-binding proteins in human colostrum and milk and rat milk. A corticosteroid-binding protein was detected in the whey of human colostrum and milk which resembles serum corticosteroid-binding globulin in certain respects: the equilibrium association constants for cortisol and progesterone binding and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar, and cortisol andd progesterone competed strongly for binding to the same site in each instance. Dexamethasone-binding activity could not be detected. The concentration of corticosteroid-binding protein in the colostrum obtained before parturition is about 0.1 muM; the concentration declines rapidly after parturition to about 0.01 muM. A corticosteroid-binding protein was found, also, in the whey of mature rat milk at levels of about 0.3 muM. This protein resembles rat serum corticosteroid-binding globulin: the equilibrium association constants for cortisol, corticosterone, and progesterone binding, and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar; the elution behavior of the respective proteins on anion exchange chromatography with DEAE-Sephadex A-50 was similar, also. Identity of the corticosteroid-binding proteins in whey with corticosteroid-binding globulin in serum is not presumed, however. Rat and human whey exhibited very little testosterone- or 17 beta-estradiol-binding activity. It is suggested the corticosteroid-binding proteins may play a significant physiological role in regulating the concentration of the bound and unbound forms of progesterone and cortisol in the fluids bathing the epithelial cells lining the mammary ducts and acini."} {"id": "PMID:182695", "title": "In vitro activation of rat liver phenylalanine hydroxylase by phosphorylation.", "content": "Essentially pure phenylalanine hydroxylase from rat liver can be activated between 2.5- and 3.0-fold by treatment with Mg2+, ATP, protein kinase, and cyclic AMP. The activation is seen when the hydroxylase is assayed in the presence of tetrahydrobiopterin, but not in the presence of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine. In the presence of [gamma-32P]ATP, activation is accompanied by incorporation of 32P into the protein to the extent of 0.7 mol/mol of hydroxylase subunit (Mr = 50,000). Cehmical analysis of the untreated enzyme shows that it already contains about 0.3 mol of Pi/mol of hydroxylase. These results suggest that the activity of the hydroxylase may be regulated by phosphorylation.", "contents": "In vitro activation of rat liver phenylalanine hydroxylase by phosphorylation. Essentially pure phenylalanine hydroxylase from rat liver can be activated between 2.5- and 3.0-fold by treatment with Mg2+, ATP, protein kinase, and cyclic AMP. The activation is seen when the hydroxylase is assayed in the presence of tetrahydrobiopterin, but not in the presence of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine. In the presence of [gamma-32P]ATP, activation is accompanied by incorporation of 32P into the protein to the extent of 0.7 mol/mol of hydroxylase subunit (Mr = 50,000). Cehmical analysis of the untreated enzyme shows that it already contains about 0.3 mol of Pi/mol of hydroxylase. These results suggest that the activity of the hydroxylase may be regulated by phosphorylation."} {"id": "PMID:182696", "title": "Phosphorylation of rat liver ribonucleic acid polymerase I by nuclear protein kinases.", "content": "Phosphorylation of rat liver RNA polymerase I occurred when intact rat liver nuclei were incubated with [gamma32P]ATP and N6,O2' dibutyryl cyclic 3':5'-AMP. In addition, partially purified RNA polymerase I could be phosphorylated in vitro by an endogenous protein kinase. Phosphorylation by either method was followed by extensive purification of the enzyme. This revealed that 32P remained bound to the enzyme throughout purification. Analysis of the homogeneous labeled protein by polyacrylamide gel electrophoresis under nondenaturing conditions followed by autoradiography revealed that only one of the two forms of RNA polymerase I in rat liver nuclei was phosphorylated. RNA polymerase II was not phosphorylated in intact nuclei. Polyacrylamide gel electrophoresis of the phosphorylated RNA polymerase I in the presence of 0.1% sodium dodecyl sulfate followed by autoradiography demonstrated that the 32P was located primarily on enzyme subunits SA1, SA3, and SA5-SA6. High voltage paper electrophoresis of a partial acid hydrolysate of phosphorylated RNA polymerase I revealed that both serine and threonine residues were phosphroylated. N6,O2'-Dibutyryl cyclic 3':5'-AMP stimulated endogenous RNA polymerase I activity and endogenous nuclear protein phosphorylation in intact nuclei. These results suggest that phosphorylation of RNA polymerase I by nuclear protein kinases may play a role in the control of transcription in mammalian cells.", "contents": "Phosphorylation of rat liver ribonucleic acid polymerase I by nuclear protein kinases. Phosphorylation of rat liver RNA polymerase I occurred when intact rat liver nuclei were incubated with [gamma32P]ATP and N6,O2' dibutyryl cyclic 3':5'-AMP. In addition, partially purified RNA polymerase I could be phosphorylated in vitro by an endogenous protein kinase. Phosphorylation by either method was followed by extensive purification of the enzyme. This revealed that 32P remained bound to the enzyme throughout purification. Analysis of the homogeneous labeled protein by polyacrylamide gel electrophoresis under nondenaturing conditions followed by autoradiography revealed that only one of the two forms of RNA polymerase I in rat liver nuclei was phosphorylated. RNA polymerase II was not phosphorylated in intact nuclei. Polyacrylamide gel electrophoresis of the phosphorylated RNA polymerase I in the presence of 0.1% sodium dodecyl sulfate followed by autoradiography demonstrated that the 32P was located primarily on enzyme subunits SA1, SA3, and SA5-SA6. High voltage paper electrophoresis of a partial acid hydrolysate of phosphorylated RNA polymerase I revealed that both serine and threonine residues were phosphroylated. N6,O2'-Dibutyryl cyclic 3':5'-AMP stimulated endogenous RNA polymerase I activity and endogenous nuclear protein phosphorylation in intact nuclei. These results suggest that phosphorylation of RNA polymerase I by nuclear protein kinases may play a role in the control of transcription in mammalian cells."} {"id": "PMID:182698", "title": "Treatment of fractures of the femoral neck by replacement with the Thompson prosthesis.", "content": "The case histories of 361 subcapital fractures of the femoral neck in 354 patients treated by primary replacement with the cemented Thompson prosthesis were reviewed, and 156 survivors were seen at follow-up. The average age was eighty-one years. Three hundred and thirty fractures occurred in women and thirty-one in men. The antero-lateral approach to the hip was used at all operations because it allows immediate and unrestricted mobilisation after operation. It is considered that this method is the best treatment in the rehabilitation of elderly patients after high femoral neck fractures, because of its low morbidity and high success rate in returning the geriatric orthopaedic patient to independence. The results after an average of just over three years were available for 161 hips in 156 patients studied at follow-up. Of these, 132 (82 per cent) were satisfactory. Most of the unsatisfactory results were in patients under seventy-five years of age. Out of the whole group of 361 hips treated the important early complications were wound infections in seventeen hips 4-7 per cent), all of which resolved, and dislocation in seven hips (2 per cent). Forty-six patients (12-9 per cent) died during the first four weeks after operation, their average age being eighty-five. One hundred and seventy-one patients (47-4 per cent) were discharged from hospital within under four weeks of the operation. Acetabular erosion and loosening are shown to be the important later complications. Three patients had late sepsis.", "contents": "Treatment of fractures of the femoral neck by replacement with the Thompson prosthesis. The case histories of 361 subcapital fractures of the femoral neck in 354 patients treated by primary replacement with the cemented Thompson prosthesis were reviewed, and 156 survivors were seen at follow-up. The average age was eighty-one years. Three hundred and thirty fractures occurred in women and thirty-one in men. The antero-lateral approach to the hip was used at all operations because it allows immediate and unrestricted mobilisation after operation. It is considered that this method is the best treatment in the rehabilitation of elderly patients after high femoral neck fractures, because of its low morbidity and high success rate in returning the geriatric orthopaedic patient to independence. The results after an average of just over three years were available for 161 hips in 156 patients studied at follow-up. Of these, 132 (82 per cent) were satisfactory. Most of the unsatisfactory results were in patients under seventy-five years of age. Out of the whole group of 361 hips treated the important early complications were wound infections in seventeen hips 4-7 per cent), all of which resolved, and dislocation in seven hips (2 per cent). Forty-six patients (12-9 per cent) died during the first four weeks after operation, their average age being eighty-five. One hundred and seventy-one patients (47-4 per cent) were discharged from hospital within under four weeks of the operation. Acetabular erosion and loosening are shown to be the important later complications. Three patients had late sepsis."} {"id": "PMID:182699", "title": "Ecto-ganglioside-sialidase activity of herpes simplex virus-transformed hamster embryo fibroblasts.", "content": "Cellular location of ganglioside-sialidase activity was determined in confluent hamster embryo fibroblasts transformed with herpes simplex virus type 2. Approximately equal specific activities of ganglioside-sialidase activity were found to be associated with the crude lysosomal and crude plasma membrane fractions isolated from whole cell homogenates. Whole transformed cells hydrolyzed exogenous ganglioside substrate, suggesting a partial location of the cellular sialidase on the outer surface of the plasma membrane of these cells. Intact cells were treated with the diazonium salt of sulfanilic acid, a nonpenetrating reagent inhibitory to ecto-enzymes (DePierre, J.W., and M. L. Karnovsky. 1974. J. Biol. Chem. 249:7111-7120). Cytoplasmic lactate dehydrogenase activity was not inhibited by this treatment, and mitochondrial succinate dehydrogenase activity was inhibited only 10%, indicating that intracellular enzymes were not affected. 5'-Nucleotidase activity was diminished 90%, and sialidase very rapidly lost 40% of its exogenously directed activity. These results show that, in herpes simplex virus-transformed fibroblasts, ganglioside-sialidase is both a lysosomal and a plasma membrane enzyme. The plasma membrane sialidase is capable of acting on endogenous plasma membrane sialolipids and also functions in the cultured transformed cell as an ecto-enzyme which can attack exogenous substrates.", "contents": "Ecto-ganglioside-sialidase activity of herpes simplex virus-transformed hamster embryo fibroblasts. Cellular location of ganglioside-sialidase activity was determined in confluent hamster embryo fibroblasts transformed with herpes simplex virus type 2. Approximately equal specific activities of ganglioside-sialidase activity were found to be associated with the crude lysosomal and crude plasma membrane fractions isolated from whole cell homogenates. Whole transformed cells hydrolyzed exogenous ganglioside substrate, suggesting a partial location of the cellular sialidase on the outer surface of the plasma membrane of these cells. Intact cells were treated with the diazonium salt of sulfanilic acid, a nonpenetrating reagent inhibitory to ecto-enzymes (DePierre, J.W., and M. L. Karnovsky. 1974. J. Biol. Chem. 249:7111-7120). Cytoplasmic lactate dehydrogenase activity was not inhibited by this treatment, and mitochondrial succinate dehydrogenase activity was inhibited only 10%, indicating that intracellular enzymes were not affected. 5'-Nucleotidase activity was diminished 90%, and sialidase very rapidly lost 40% of its exogenously directed activity. These results show that, in herpes simplex virus-transformed fibroblasts, ganglioside-sialidase is both a lysosomal and a plasma membrane enzyme. The plasma membrane sialidase is capable of acting on endogenous plasma membrane sialolipids and also functions in the cultured transformed cell as an ecto-enzyme which can attack exogenous substrates."} {"id": "PMID:182700", "title": "Cell to substratum adhesion-promoting activity released by normal and virus-transformed cells in culture.", "content": "It is demonstrated here that cultured fibroblasts release into their medium a nondialyzable, protease-sensitive factor(s) capable of promoting the adhesion and spreading of virus-transformed rat fibroblasts on a plastic substratum. A relatively sensitive biological assay is described for quantitation of the adhesion-promoting factor (APF) activity in serum-free, conditioned medium harvested from the cultures. Evidence is presented which indicates that the primary mode of action of the APF is by binding to and modifying the properties of the substratum. Conditioned media harvested after 24 h of incubation in similarly populated cultures of normal fibroblasts of diverse animal species exhibited similar levels of APF activity. However, conditioned media obtained from Rous sarcoma virus (Prague strain)-transformed and avian sarcoma virus B77-transformed rat fibroblasts exhibited three- to sixfold lower levels of APF activity than media conditioned in parallel cultures of heterologous or homologous normal fibroblasts. Cultivation of B77 virus-transformed rat cells in the presence of dibutyryl cyclic AMP and theophylline led to as much as a sevenfold increase in the level of APF activity appearing in the culture medium, with a concomitant increase in the adhesiveness of the cells to the culture substratum. The results support the role of extracellular macromolecules in cell to substratum adhesion. It is postulated that the reduced adhesiveness of transformed cells to a substratum may be at least partially owing to a deficiency in the production and/or release of APF-like macromolecules.", "contents": "Cell to substratum adhesion-promoting activity released by normal and virus-transformed cells in culture. It is demonstrated here that cultured fibroblasts release into their medium a nondialyzable, protease-sensitive factor(s) capable of promoting the adhesion and spreading of virus-transformed rat fibroblasts on a plastic substratum. A relatively sensitive biological assay is described for quantitation of the adhesion-promoting factor (APF) activity in serum-free, conditioned medium harvested from the cultures. Evidence is presented which indicates that the primary mode of action of the APF is by binding to and modifying the properties of the substratum. Conditioned media harvested after 24 h of incubation in similarly populated cultures of normal fibroblasts of diverse animal species exhibited similar levels of APF activity. However, conditioned media obtained from Rous sarcoma virus (Prague strain)-transformed and avian sarcoma virus B77-transformed rat fibroblasts exhibited three- to sixfold lower levels of APF activity than media conditioned in parallel cultures of heterologous or homologous normal fibroblasts. Cultivation of B77 virus-transformed rat cells in the presence of dibutyryl cyclic AMP and theophylline led to as much as a sevenfold increase in the level of APF activity appearing in the culture medium, with a concomitant increase in the adhesiveness of the cells to the culture substratum. The results support the role of extracellular macromolecules in cell to substratum adhesion. It is postulated that the reduced adhesiveness of transformed cells to a substratum may be at least partially owing to a deficiency in the production and/or release of APF-like macromolecules."} {"id": "PMID:182701", "title": "Fibrils attached to the nuclear pore prevent egress of SV40 particles from the infected nucleus.", "content": "SV40 particles can apparently enter the nucleus intact. However, they do not leave the nucleus despite the high concentration present during the productive phase. We found structural evidence that SV40 virus is prevented from approaching the most likely site of exit, the nuclear pore complex. From these images, it is concluded that the fibrils attached to the nuclear pore complex prevent egress of SV40 particles from the infected nucleus.", "contents": "Fibrils attached to the nuclear pore prevent egress of SV40 particles from the infected nucleus. SV40 particles can apparently enter the nucleus intact. However, they do not leave the nucleus despite the high concentration present during the productive phase. We found structural evidence that SV40 virus is prevented from approaching the most likely site of exit, the nuclear pore complex. From these images, it is concluded that the fibrils attached to the nuclear pore complex prevent egress of SV40 particles from the infected nucleus."} {"id": "PMID:182702", "title": "Cytotoxicity for tumor cells of cationic proteins from human neutrophil granules.", "content": "Cationic proteins purified from human polymorphonuclear leukocyte granules exert a cytotoxic effect on mammalian tumor cells. This effect is time and concentration dependent, is inhibited by the anionic agent heparin, and is enhanced by preheating the cationic proteins. Other strongly basic proteins (histone, protamine) also exhibited cytotoxic activity. Myeloperoxidase isolated from human leukocytes is cytotoxic when combined with H2O2 and chloride. Under these conditions, the potency of the myeloperoxidase-mediated system is greater than that of the cationic proteins.", "contents": "Cytotoxicity for tumor cells of cationic proteins from human neutrophil granules. Cationic proteins purified from human polymorphonuclear leukocyte granules exert a cytotoxic effect on mammalian tumor cells. This effect is time and concentration dependent, is inhibited by the anionic agent heparin, and is enhanced by preheating the cationic proteins. Other strongly basic proteins (histone, protamine) also exhibited cytotoxic activity. Myeloperoxidase isolated from human leukocytes is cytotoxic when combined with H2O2 and chloride. Under these conditions, the potency of the myeloperoxidase-mediated system is greater than that of the cationic proteins."} {"id": "PMID:182703", "title": "Stimulation by N6,O2'-dibutyrul andenosine 3',5'-cyclic monophosphate of RNA and DNA synthesis and of cell proliferation of rat hepatocytes in primary tissue culture.", "content": "The effects of DBcAMP in doses from 1.5 x 10(-8) to 1.5 x 10(-3) M on the compartmental apparent surface area (ASA) and (5(-3H)uridine radioactivity concentration (URC), (methyl-3H)thymidine labelling index per 1 hour ([Me-3H]Tdr LI/h) and per cent mitotic index (MI%) and colchicine metaphase index (CMI%) of young rat differentiated hepatocytes in primary tissue culture were investigated by morphometric and radioautographie methods. In these cells DBcAMP was found to elicit: (1) progressive increments in the ASA of nucleoli, karyoplasm and cytoplasm; (2) peak increases in nucleolar URC at 1.5 x 10(-8) and 10(-5) M, but a slight decrease at 1.5 x 10(-3) M; (3) singificant increments in karyoplasmic and total nuclear URC at all doses, except at 1.5 x 10(-6) and 10(-4) M, when such parameters remained at control levels; (4) steady and progressive increases in cytoplasmic and total cell URC values; (5) marked increments in (Me-3H)Tdr LI/h, MI% and CMI% up to the dose of 1.5 x 10(-4) M, but at 1.5 x 10(-3) M these parameters were found to be either much less enhanced or to approach closely to control values. cAMP in doses from 1.5 x 10(-8) to 10(-4) M also markedly incremented the in vitro hepatocyte CMI%, while having a lesser stimulatory effect at 1.5 x 10(-3)M. Finally of the various possible metabolites of DBcAMP administered at 1.5 x 10(-8) M to liver cultures, N6- and O2'-MBcAMP and, again, cAMP significantly increased the CMI%, of cultured hepatocytes, whereas 5'-AMP, adenosine and allantoin had no significant effect and Na-butyrate slightly decreased it. The present observations strengthen the hypothesis that cAMP and its butyrated derivatives, by possibly amplifying the template activity of the liver chromatin, accelerate the flow of differentiated primary young rat hepatocytes into the various stages of the mitotic cell cycle.", "contents": "Stimulation by N6,O2'-dibutyrul andenosine 3',5'-cyclic monophosphate of RNA and DNA synthesis and of cell proliferation of rat hepatocytes in primary tissue culture. The effects of DBcAMP in doses from 1.5 x 10(-8) to 1.5 x 10(-3) M on the compartmental apparent surface area (ASA) and (5(-3H)uridine radioactivity concentration (URC), (methyl-3H)thymidine labelling index per 1 hour ([Me-3H]Tdr LI/h) and per cent mitotic index (MI%) and colchicine metaphase index (CMI%) of young rat differentiated hepatocytes in primary tissue culture were investigated by morphometric and radioautographie methods. In these cells DBcAMP was found to elicit: (1) progressive increments in the ASA of nucleoli, karyoplasm and cytoplasm; (2) peak increases in nucleolar URC at 1.5 x 10(-8) and 10(-5) M, but a slight decrease at 1.5 x 10(-3) M; (3) singificant increments in karyoplasmic and total nuclear URC at all doses, except at 1.5 x 10(-6) and 10(-4) M, when such parameters remained at control levels; (4) steady and progressive increases in cytoplasmic and total cell URC values; (5) marked increments in (Me-3H)Tdr LI/h, MI% and CMI% up to the dose of 1.5 x 10(-4) M, but at 1.5 x 10(-3) M these parameters were found to be either much less enhanced or to approach closely to control values. cAMP in doses from 1.5 x 10(-8) to 10(-4) M also markedly incremented the in vitro hepatocyte CMI%, while having a lesser stimulatory effect at 1.5 x 10(-3)M. Finally of the various possible metabolites of DBcAMP administered at 1.5 x 10(-8) M to liver cultures, N6- and O2'-MBcAMP and, again, cAMP significantly increased the CMI%, of cultured hepatocytes, whereas 5'-AMP, adenosine and allantoin had no significant effect and Na-butyrate slightly decreased it. The present observations strengthen the hypothesis that cAMP and its butyrated derivatives, by possibly amplifying the template activity of the liver chromatin, accelerate the flow of differentiated primary young rat hepatocytes into the various stages of the mitotic cell cycle."} {"id": "PMID:182704", "title": "Detection of sodium alkanesulphonates and alkylbenzenesulphonates by polyamide thin-layer chromatography.", "content": "A thin-layer chromatographic method was investigated in which two series of sodium alkanesulphonates (C4-C18) and alkylbenzenesulphonates (C0-C14) were separated. All of the compounds tested were clearly separated on polyamide layers with aqueous ammonia-pyridine and aqueous ammonia-pyridine-methanol systems and detected with high sensitivity by spraying with a pynacryptol yellow reagent and then observing under UV light (253.6nm).", "contents": "Detection of sodium alkanesulphonates and alkylbenzenesulphonates by polyamide thin-layer chromatography. A thin-layer chromatographic method was investigated in which two series of sodium alkanesulphonates (C4-C18) and alkylbenzenesulphonates (C0-C14) were separated. All of the compounds tested were clearly separated on polyamide layers with aqueous ammonia-pyridine and aqueous ammonia-pyridine-methanol systems and detected with high sensitivity by spraying with a pynacryptol yellow reagent and then observing under UV light (253.6nm)."} {"id": "PMID:182708", "title": "Separation of drug substances by modern liquid chromatography on silver impregnated silica gels.", "content": "The use of silver halide impregnated supports for high-pressure liquid chromatographic (HPLC) and thin-layer chromatographic (TLC) analysis of drug substances has been studied. Successful separations of xanthines and mixtures containing barbiturates, xanthines, ergot alkaloids, and tropane alkaloids have been achieved with isocratic conditions or by using simple gradients. The Ag-supports show a similar behavior as many chemically bonded stationary phases, such as modification fo adsorption sites on silica gel to give lower retention but better specificity; rapid reconditioning in connection with gradient elution (3-5 minutes). Reasonable cost, simplicity of preparation and usage, and good chemical and physical stability render the silver halide phases applicable in routine analysis and quite competitive with many commercially available chemically bonded stationary phases.", "contents": "Separation of drug substances by modern liquid chromatography on silver impregnated silica gels. The use of silver halide impregnated supports for high-pressure liquid chromatographic (HPLC) and thin-layer chromatographic (TLC) analysis of drug substances has been studied. Successful separations of xanthines and mixtures containing barbiturates, xanthines, ergot alkaloids, and tropane alkaloids have been achieved with isocratic conditions or by using simple gradients. The Ag-supports show a similar behavior as many chemically bonded stationary phases, such as modification fo adsorption sites on silica gel to give lower retention but better specificity; rapid reconditioning in connection with gradient elution (3-5 minutes). Reasonable cost, simplicity of preparation and usage, and good chemical and physical stability render the silver halide phases applicable in routine analysis and quite competitive with many commercially available chemically bonded stationary phases."} {"id": "PMID:182709", "title": "A method for the gas chromatographic determination of vitamin D and related structures.", "content": "A procedure is described for the separation of Vitamin D and related compounds by gas-liquid chromatography using flame ionization detection. The method involves a two-step conversion: isomerization to the corresponding (all trans) isotachysterol(s) followed by methyl ether derivatization of the alcohol group(s). The procedure provides a means for identification as well as a possible basis for quantitation of Vitamin D and analogs.", "contents": "A method for the gas chromatographic determination of vitamin D and related structures. A procedure is described for the separation of Vitamin D and related compounds by gas-liquid chromatography using flame ionization detection. The method involves a two-step conversion: isomerization to the corresponding (all trans) isotachysterol(s) followed by methyl ether derivatization of the alcohol group(s). The procedure provides a means for identification as well as a possible basis for quantitation of Vitamin D and analogs."} {"id": "PMID:182710", "title": "Estrone and estradiol in patients with cirrhosis of the liver: effects of ACTH and dexamethasone.", "content": "To study the influence of the adrenal gland on plasma estrogen levels in male patients with hepatic cirrhosis, estrone and estradiol were measured under a variety of experimental conditions. Compared to controls, estradiol levels were moderately elevated by 26% (P is less than 0.05) in patients with hepatic cirrhosis (28.5 +/- 5.4 vs. 36.0 +/- 4.7 pg/ml plasma; n: 12), whereas estrone levels exhibited a two- to threefold increase under basal conditions (32.5 +/- 5.6 vs. 67.8 +/- 20.8 pg/ml; P is less than 0.01). ACTH application resulted in a striking increase in plasma estrone levels in both patients with hepatic cirrhosis and in normal subjects (61.8 +/- 27.5 vs. 27.3 +/- 7.8 pg/ml). During stimulation with ACTH, estradiol levels showed no significant changes. After suppression of the adrenal gland by dexamethasone administered for 5 days, plasma concentrations of estrone and estradiol were found to be reduced. The absolute decrease of estrone was significantly greater in patients with hepatic cirrhosis than in healthy male subjects (35.5 +/- 12.6 vs. 21.3 +/- 6.0 pg/ml; P is less than 0.05; n: 8). Estrogen values, however, were still high in patients with hepatic cirrhosis after 5 days of dexamethasone administration (37.1 +/- 17.6 pg estrone/ml and 23.9 +/- 3.6 pg estradiol/ml plasma). It is suggested that elevated plasma values of estrogens in this disorder may be derived predominantly from adrenal production. Peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels of estrogens in patients with hepatic cirrhosis.", "contents": "Estrone and estradiol in patients with cirrhosis of the liver: effects of ACTH and dexamethasone. To study the influence of the adrenal gland on plasma estrogen levels in male patients with hepatic cirrhosis, estrone and estradiol were measured under a variety of experimental conditions. Compared to controls, estradiol levels were moderately elevated by 26% (P is less than 0.05) in patients with hepatic cirrhosis (28.5 +/- 5.4 vs. 36.0 +/- 4.7 pg/ml plasma; n: 12), whereas estrone levels exhibited a two- to threefold increase under basal conditions (32.5 +/- 5.6 vs. 67.8 +/- 20.8 pg/ml; P is less than 0.01). ACTH application resulted in a striking increase in plasma estrone levels in both patients with hepatic cirrhosis and in normal subjects (61.8 +/- 27.5 vs. 27.3 +/- 7.8 pg/ml). During stimulation with ACTH, estradiol levels showed no significant changes. After suppression of the adrenal gland by dexamethasone administered for 5 days, plasma concentrations of estrone and estradiol were found to be reduced. The absolute decrease of estrone was significantly greater in patients with hepatic cirrhosis than in healthy male subjects (35.5 +/- 12.6 vs. 21.3 +/- 6.0 pg/ml; P is less than 0.05; n: 8). Estrogen values, however, were still high in patients with hepatic cirrhosis after 5 days of dexamethasone administration (37.1 +/- 17.6 pg estrone/ml and 23.9 +/- 3.6 pg estradiol/ml plasma). It is suggested that elevated plasma values of estrogens in this disorder may be derived predominantly from adrenal production. Peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels of estrogens in patients with hepatic cirrhosis."} {"id": "PMID:182711", "title": "Effects of estrogens on adrenal 3 beta-hydroxysteroid dehydrogenase in ovariectomized women.", "content": "The acute and chronic effects of estradiol (E2) on the serum levels of four delta5,3-beta hydroxysteroids and their four delta4, 3-keto products were studied in four ovariectomized women with and without adrenal stimulation by ACTH. Six hour infusions of saline and of synthetic 1-24 ACTH were administered and later repeated with a two hour infusion of E2 50 mug/h. The patients were then given 50 mug of ethinyl estradiol (EE2) p.o. for 4 to 6 weeks and the control and ACTH infusions were again repeated. Levels of pregnenolone3 (Pe), 17alpha-hydroxypregnenolone (17 Pe), progesterone (Po), 17alpha-hydroxyprogesterone (17 Po), dehydroepiandrosterone (DHEA), androstenedione (Adione), androstenediol (Adiol), and testosterone (T), as well as cortisol and DHEA-sulfate were measured by radioimmunoassay on serum samples taken at 1200 and 1300 h. There was no significant effect of E2 or EE2 in the doses administered with or without exogenous ACTH on 3 betaOHSD activity as reflected in absolute steroid levels or in the ratio of concentrations of each delta5:delta4 steroid pair. During the 4th and 5th hour of ACTH infusion, the plasma level of 17 Pe (mean 22.5-fold stimulation) was most elevated, followed by 17 Po (12.5-fold), Pe (10-fold), cortisol (5.9-fold) and Po (4.5-fold), with smaller increases for the other steroids. These results, as well as the pattern of change in plasma levels in one of the subjects in whom fifteen minute samples were measured, provide further evidence suggesting that the major pathway for cortisol biosynthesis in vivo proceeds from Pe via 17 Pe, and not via Po.", "contents": "Effects of estrogens on adrenal 3 beta-hydroxysteroid dehydrogenase in ovariectomized women. The acute and chronic effects of estradiol (E2) on the serum levels of four delta5,3-beta hydroxysteroids and their four delta4, 3-keto products were studied in four ovariectomized women with and without adrenal stimulation by ACTH. Six hour infusions of saline and of synthetic 1-24 ACTH were administered and later repeated with a two hour infusion of E2 50 mug/h. The patients were then given 50 mug of ethinyl estradiol (EE2) p.o. for 4 to 6 weeks and the control and ACTH infusions were again repeated. Levels of pregnenolone3 (Pe), 17alpha-hydroxypregnenolone (17 Pe), progesterone (Po), 17alpha-hydroxyprogesterone (17 Po), dehydroepiandrosterone (DHEA), androstenedione (Adione), androstenediol (Adiol), and testosterone (T), as well as cortisol and DHEA-sulfate were measured by radioimmunoassay on serum samples taken at 1200 and 1300 h. There was no significant effect of E2 or EE2 in the doses administered with or without exogenous ACTH on 3 betaOHSD activity as reflected in absolute steroid levels or in the ratio of concentrations of each delta5:delta4 steroid pair. During the 4th and 5th hour of ACTH infusion, the plasma level of 17 Pe (mean 22.5-fold stimulation) was most elevated, followed by 17 Po (12.5-fold), Pe (10-fold), cortisol (5.9-fold) and Po (4.5-fold), with smaller increases for the other steroids. These results, as well as the pattern of change in plasma levels in one of the subjects in whom fifteen minute samples were measured, provide further evidence suggesting that the major pathway for cortisol biosynthesis in vivo proceeds from Pe via 17 Pe, and not via Po."} {"id": "PMID:182712", "title": "ACTH and cortisol responses to glucagon stimulation.", "content": "The effect of the intramuscular injection of various doses of glucagon in 15 healthy subjects was studied. Significant elevations of plasma ACTH, and cortisol were found to occur 3 h after the administration of 4 mg of crystalline glucagon. Mean levels in 7 subjects were for ACTH 44 +/- 30 (SD) pg/ml, and for cortisol 14 +/- 6 (SD) mug/100 ml at the beginning of the test, and rose to 109 +/- 48 (SD) pg/ml and to 23 +/- 5 (SD) mug/100 ml respectively following glucagon. The peak response of ACTH and cortisol was preceded by a significant rise of plasma insulin, by a fall of the blood glucose, which was initially increased by the administration of glucagon, and by the symptoms of nausea and sweating. This study demonstrates that the intramuscluar administration of glucagon (4 mg) provids a potent stimulus to ACTH and cortisol secretion in healthy subjects.", "contents": "ACTH and cortisol responses to glucagon stimulation. The effect of the intramuscular injection of various doses of glucagon in 15 healthy subjects was studied. Significant elevations of plasma ACTH, and cortisol were found to occur 3 h after the administration of 4 mg of crystalline glucagon. Mean levels in 7 subjects were for ACTH 44 +/- 30 (SD) pg/ml, and for cortisol 14 +/- 6 (SD) mug/100 ml at the beginning of the test, and rose to 109 +/- 48 (SD) pg/ml and to 23 +/- 5 (SD) mug/100 ml respectively following glucagon. The peak response of ACTH and cortisol was preceded by a significant rise of plasma insulin, by a fall of the blood glucose, which was initially increased by the administration of glucagon, and by the symptoms of nausea and sweating. This study demonstrates that the intramuscluar administration of glucagon (4 mg) provids a potent stimulus to ACTH and cortisol secretion in healthy subjects."} {"id": "PMID:182713", "title": "Stability of pseudorabies virus during freeze-drying and storage: effect of suspending media.", "content": "The effect of suspending media on the stability of pseudorabies virus upon freeze-drying and subsequent storage was studied. A variety of media was tested, including: sodium glutamate; sucrose; lactose; lactalbumin hydrolysate; peptone; a combination of sucrose, dextran, and glutamate; and various combinations of sucrose, glutamate, and potassium phosphates. Suspending media containing glutamate, either alone or in combination with sucrose and either dextran or phosphates, afforded the greatest degree of protection during the freeze-drying process and upon storage. Some possible functions of these additives in preventing injury to the virus during freezing and drying have been suggested.", "contents": "Stability of pseudorabies virus during freeze-drying and storage: effect of suspending media. The effect of suspending media on the stability of pseudorabies virus upon freeze-drying and subsequent storage was studied. A variety of media was tested, including: sodium glutamate; sucrose; lactose; lactalbumin hydrolysate; peptone; a combination of sucrose, dextran, and glutamate; and various combinations of sucrose, glutamate, and potassium phosphates. Suspending media containing glutamate, either alone or in combination with sucrose and either dextran or phosphates, afforded the greatest degree of protection during the freeze-drying process and upon storage. Some possible functions of these additives in preventing injury to the virus during freezing and drying have been suggested."} {"id": "PMID:182714", "title": "Recovery of applied human leukocyte interferon from the nasal mucosa of chimpanzees and humans.", "content": "Intranasally applied human leukocyte interferon was recovered locally in 9 of 10 chimpanzees and 3 of 3 human volunteers tested. A 5- to 50-fold reduction in interferon was observed over 60 min.", "contents": "Recovery of applied human leukocyte interferon from the nasal mucosa of chimpanzees and humans. Intranasally applied human leukocyte interferon was recovered locally in 9 of 10 chimpanzees and 3 of 3 human volunteers tested. A 5- to 50-fold reduction in interferon was observed over 60 min."} {"id": "PMID:182715", "title": "Continuing search for the etiology of cat scratch disease.", "content": "Fifty cat scratch disease patients were tested for antibodies against candidate etiological agents, with inconclusive results. Future research should emphasize new viral isolation methods to discover the elusive agent.", "contents": "Continuing search for the etiology of cat scratch disease. Fifty cat scratch disease patients were tested for antibodies against candidate etiological agents, with inconclusive results. Future research should emphasize new viral isolation methods to discover the elusive agent."} {"id": "PMID:182716", "title": "Plaque reduction neutralization test for human cytomegalovirus based upon enhanced uptake of neutral red by virus-infected cells.", "content": "Foci of cells infected with human cytomegalovirus were noted to stain more intensely than uninfected cells with neutral red, and this provided the basis for development of a plaque assay and plaque reduction neutralization test for cytomegalovirus. Plaques demonstrable by neutral red staining could be counted at 8 days after infection; thus, results could be obtained earlier than for plaque assay systems based upon the viral cytopathic effect, a fewer manipulations were required for staining cell monolayers to demonstrate plaques. Certain variables affecting plaque size and numbers and antibody titers were defined. Addition of fresh guinea pig complement to the reaction mixtures markedly enhanced cytomegalovirus-neutralizing antibody titers of hyperimmune animal sera, but titers of human sera were enhanced only two-or fourfold.", "contents": "Plaque reduction neutralization test for human cytomegalovirus based upon enhanced uptake of neutral red by virus-infected cells. Foci of cells infected with human cytomegalovirus were noted to stain more intensely than uninfected cells with neutral red, and this provided the basis for development of a plaque assay and plaque reduction neutralization test for cytomegalovirus. Plaques demonstrable by neutral red staining could be counted at 8 days after infection; thus, results could be obtained earlier than for plaque assay systems based upon the viral cytopathic effect, a fewer manipulations were required for staining cell monolayers to demonstrate plaques. Certain variables affecting plaque size and numbers and antibody titers were defined. Addition of fresh guinea pig complement to the reaction mixtures markedly enhanced cytomegalovirus-neutralizing antibody titers of hyperimmune animal sera, but titers of human sera were enhanced only two-or fourfold."} {"id": "PMID:182717", "title": "Genetic Transformation as a tool for detection of Neisseria gonorrhoeae.", "content": "A rapid method for the detection of Neisseria gonorrhoeae, making use of the ability of deoxyribonucleic acid samples from clinically isolated strains of this organism to transform nutritional mutants of a particular strain of N. gonorrhoeae, has been described. In addition to using isolated cultures, transforming deoxyribonucleic acid can be obtained directly from the material that adheres to swabs of the cervix or the urethra. The time interval for transfer of swabs to the diagnostic laboratory is not a significant factor. It is not necessary to use pure cultures on primary isolation plates to obtain definitive results. Nongonorrhoeae neisserias, as well as a large variety of commonly encountered unrelated bacteria, do not react or interfere in the transformation assay when using one of the mutant strains under a standardized set of conditions. The entire assay can be completed in less than 24 h. It has also been shown that type T4 cells of the strain of N. gonorrhoeae employed in the present study are competent for genetic transformation, although type T4 cells are transformed at a significantly lower frequency than are type T2 cells of the same strain.", "contents": "Genetic Transformation as a tool for detection of Neisseria gonorrhoeae. A rapid method for the detection of Neisseria gonorrhoeae, making use of the ability of deoxyribonucleic acid samples from clinically isolated strains of this organism to transform nutritional mutants of a particular strain of N. gonorrhoeae, has been described. In addition to using isolated cultures, transforming deoxyribonucleic acid can be obtained directly from the material that adheres to swabs of the cervix or the urethra. The time interval for transfer of swabs to the diagnostic laboratory is not a significant factor. It is not necessary to use pure cultures on primary isolation plates to obtain definitive results. Nongonorrhoeae neisserias, as well as a large variety of commonly encountered unrelated bacteria, do not react or interfere in the transformation assay when using one of the mutant strains under a standardized set of conditions. The entire assay can be completed in less than 24 h. It has also been shown that type T4 cells of the strain of N. gonorrhoeae employed in the present study are competent for genetic transformation, although type T4 cells are transformed at a significantly lower frequency than are type T2 cells of the same strain."} {"id": "PMID:182718", "title": "Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. Deficient 5alpha-dihydrotestosterone binding in cultured skin fibroblasts.", "content": "Maximum specific 5alpha-dihydrotestosterone (DHT) binding activity (Bmax) had been measured in intact confluent monolayers representing fibroblast strains derived form nongenital and genital (labium majus) skin of normal individuals and of 11 patients fulfilling the clinicogenetic criteria of complete testicular feminization (TF). Nine labium majus strains from adult females had a mean Bmax value three times greater than that of seven nongenital strains from adult females (33 vs. 11 fmol/mg cell protein). The Bmax results for 13 adult nongenital strains varied from 5.6 to 23.3 fmol/mg protein; the values for males and females had very similar means and ranges. The variation could not be correlated with the chronologic age of adult skin explant donors or with the in vitro age (mean population doubling level) of the cultures assayed. The Bmax activities of three nongenital strains from normal infants (two male, one female) did not exceed 5 fmol/mg protein. Seven of eight nongenital TF strains had Bmax values below 2 fmol/mg protein; the value for the eighth coincided with the lower limit of normal adults. The lower limit of DHT binding in normal labium majus strains was 15 fmol/mg protein. Three of five labial strains from patients with TF had Bmax values close to zero; the other two fell between 10 and 15 fmol/mg protein. It is apparant that labial skin fibroblast strains from clinically homogeneous patients with TF had highly variable degrees of DHT binding deficiency, and that they permit a more reliable diagnosis of severe and intermediate degrees of DHT binding deficiency than do strains of nongenital skin fibroblasts.", "contents": "Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. Deficient 5alpha-dihydrotestosterone binding in cultured skin fibroblasts. Maximum specific 5alpha-dihydrotestosterone (DHT) binding activity (Bmax) had been measured in intact confluent monolayers representing fibroblast strains derived form nongenital and genital (labium majus) skin of normal individuals and of 11 patients fulfilling the clinicogenetic criteria of complete testicular feminization (TF). Nine labium majus strains from adult females had a mean Bmax value three times greater than that of seven nongenital strains from adult females (33 vs. 11 fmol/mg cell protein). The Bmax results for 13 adult nongenital strains varied from 5.6 to 23.3 fmol/mg protein; the values for males and females had very similar means and ranges. The variation could not be correlated with the chronologic age of adult skin explant donors or with the in vitro age (mean population doubling level) of the cultures assayed. The Bmax activities of three nongenital strains from normal infants (two male, one female) did not exceed 5 fmol/mg protein. Seven of eight nongenital TF strains had Bmax values below 2 fmol/mg protein; the value for the eighth coincided with the lower limit of normal adults. The lower limit of DHT binding in normal labium majus strains was 15 fmol/mg protein. Three of five labial strains from patients with TF had Bmax values close to zero; the other two fell between 10 and 15 fmol/mg protein. It is apparant that labial skin fibroblast strains from clinically homogeneous patients with TF had highly variable degrees of DHT binding deficiency, and that they permit a more reliable diagnosis of severe and intermediate degrees of DHT binding deficiency than do strains of nongenital skin fibroblasts."} {"id": "PMID:182719", "title": "Synthesis of very low density lipoproteins in the cockerel. Effects of estrogen.", "content": "The effect of estrogen on the synthesis of plasma very low density lipoproteins (VLDL) in the cockerel was studied both in vivo and in vitro. Synthesis was studied by immunoprecipitation techniques with antisera prepared against VLDL and a major VLDL protein. VLDL were isolated from the plasma of white Leghorn hens and estrogen-treated white Leghorn cockerels by ultracentrifugal flotation at d 1.006 g/ml. After delipidation, the lipid-free proteins (apoproteins) were fractionated on Sephadex G-150 and DEAE-cellulose. Both the hen and the estrogen-treated cockerel VLDL were shown to contain an identical apoprotein with a mol wt of approximately 12,000; the apoprotein is designated fraction B. Reduction and S-carboxy-methylation of fraction B resulted in a reduction of the molecular weight by approximately one-half, indicating a dimer-monomer relationship. Antiserum prepared to the hen VLDL dimer protein gave precipitin lines of complete identity to both the hen and cockerel dimer, monomer, VLDL, apoVLDL, low density lipoproteins, and plasma; no precipitin line was formed with either hen or cockerel high density lipoproteins. After a single subcutaneous injection of diethylstilbestrol into the cockerel, plasma VLDL protein, cholesterol, and triglyceride increased, reaching a maximum 24--48 h after hormone administration. Liver slices from similarly treated animals were incubated in vitro in culture medium in the presence of [3H]lysine for 2 h. Immunoprecipitable radioactivity in VLDL increased within 2 h of diethylstilbestrol treatment and reached a maximum at 24 h; VLDL radioactivity returned to base-line levels by 72 h. At the peak of induction, newly synthesized VLDL represented 11% of the total soluble protein synthesized. When actinomycin-D (5 mg/kg) was administered simultaneously with estrogen, the induction of VLDL synthesis was totally inhibited. To determine whether the effect of estrogen on VLDL synthesis was mediated at the level of transcription, partially-purified cockerel liver mRNA was prepared from estrogen-treated animals and the mRNA activity for fraction B was quantitated in a wheat germ translation system. Fraction B mRNA was found to increase from a low base-line value to a maximum 16-24 h after estrogen treatment, returning towards baseline values at 30 h. At the peak of induction, fraction B constituted 12% of the total protein synthesized. The kinetics of induction of fraction B mRNA activity in the cell-free translation system is very similar to that observed in liver slice experiments. This finding suggests that estrogen stimulates VLDL synthesis, at least partially, by enhancing the accumulation of the mRNA for one of their major apoproteins.", "contents": "Synthesis of very low density lipoproteins in the cockerel. Effects of estrogen. The effect of estrogen on the synthesis of plasma very low density lipoproteins (VLDL) in the cockerel was studied both in vivo and in vitro. Synthesis was studied by immunoprecipitation techniques with antisera prepared against VLDL and a major VLDL protein. VLDL were isolated from the plasma of white Leghorn hens and estrogen-treated white Leghorn cockerels by ultracentrifugal flotation at d 1.006 g/ml. After delipidation, the lipid-free proteins (apoproteins) were fractionated on Sephadex G-150 and DEAE-cellulose. Both the hen and the estrogen-treated cockerel VLDL were shown to contain an identical apoprotein with a mol wt of approximately 12,000; the apoprotein is designated fraction B. Reduction and S-carboxy-methylation of fraction B resulted in a reduction of the molecular weight by approximately one-half, indicating a dimer-monomer relationship. Antiserum prepared to the hen VLDL dimer protein gave precipitin lines of complete identity to both the hen and cockerel dimer, monomer, VLDL, apoVLDL, low density lipoproteins, and plasma; no precipitin line was formed with either hen or cockerel high density lipoproteins. After a single subcutaneous injection of diethylstilbestrol into the cockerel, plasma VLDL protein, cholesterol, and triglyceride increased, reaching a maximum 24--48 h after hormone administration. Liver slices from similarly treated animals were incubated in vitro in culture medium in the presence of [3H]lysine for 2 h. Immunoprecipitable radioactivity in VLDL increased within 2 h of diethylstilbestrol treatment and reached a maximum at 24 h; VLDL radioactivity returned to base-line levels by 72 h. At the peak of induction, newly synthesized VLDL represented 11% of the total soluble protein synthesized. When actinomycin-D (5 mg/kg) was administered simultaneously with estrogen, the induction of VLDL synthesis was totally inhibited. To determine whether the effect of estrogen on VLDL synthesis was mediated at the level of transcription, partially-purified cockerel liver mRNA was prepared from estrogen-treated animals and the mRNA activity for fraction B was quantitated in a wheat germ translation system. Fraction B mRNA was found to increase from a low base-line value to a maximum 16-24 h after estrogen treatment, returning towards baseline values at 30 h. At the peak of induction, fraction B constituted 12% of the total protein synthesized. The kinetics of induction of fraction B mRNA activity in the cell-free translation system is very similar to that observed in liver slice experiments. This finding suggests that estrogen stimulates VLDL synthesis, at least partially, by enhancing the accumulation of the mRNA for one of their major apoproteins."} {"id": "PMID:182720", "title": "Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.", "content": "In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood.", "contents": "Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects. In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood."} {"id": "PMID:182721", "title": "Direct stimulation of bone resorption by thyroid hormones.", "content": "Although hypercalcemia, osteoporosis, and increased bone turnover are associated with thyrotoxicosis, no direct effects of thyroid hormones on bone metabolism have been reported previously in organ culture. We have now demonstrated that prolonged treatment with thyroxine (T4) or triiodothyronine (T3) can directly increase bone resorption in cultured fetal rat long bones as measured by the release of previously incorporated 45Ca. T4 and T3 at 1 muM to 10 nM increased 45Ca release by 10-60% of total bone 45Ca during 5 days of culture. The medium contained 4 mg/ml of bovine serum albumin to which 90% of T4 and T3 were bound, so that free concentrations were less than 0.1 muM. The response to T4 and T3 was inhibited by cortisol (1 muM) and calcitonin (100 mU/ml). Indomethacin did not inhibit T4 response suggesting that T4 stimulation of bone resorption was not mediated by increased prostaglandin synthesis by the cultured bone. Matrix resorption was demonstrated by a decrease in extracted dry weight and hydroxyproline concentration of treated bones and by histologic examination which also showed increased osteoclast activity. The effects of thyroid hormones were not only slower than those of other potent stimulators of osteoclastic bone resorption (parathyroid hormone, vitamin D metabolites, osteoclast activating factor, and prostaglandins), but the maximum response was not as great. We conclude that T4 and T3 can directly stimulate bone resorption in vitro at concentrations approaching those which occur in thyrotoxicosis. This effect may explain the disturbances of calcium metabolism seen in hyperthyroidism.", "contents": "Direct stimulation of bone resorption by thyroid hormones. Although hypercalcemia, osteoporosis, and increased bone turnover are associated with thyrotoxicosis, no direct effects of thyroid hormones on bone metabolism have been reported previously in organ culture. We have now demonstrated that prolonged treatment with thyroxine (T4) or triiodothyronine (T3) can directly increase bone resorption in cultured fetal rat long bones as measured by the release of previously incorporated 45Ca. T4 and T3 at 1 muM to 10 nM increased 45Ca release by 10-60% of total bone 45Ca during 5 days of culture. The medium contained 4 mg/ml of bovine serum albumin to which 90% of T4 and T3 were bound, so that free concentrations were less than 0.1 muM. The response to T4 and T3 was inhibited by cortisol (1 muM) and calcitonin (100 mU/ml). Indomethacin did not inhibit T4 response suggesting that T4 stimulation of bone resorption was not mediated by increased prostaglandin synthesis by the cultured bone. Matrix resorption was demonstrated by a decrease in extracted dry weight and hydroxyproline concentration of treated bones and by histologic examination which also showed increased osteoclast activity. The effects of thyroid hormones were not only slower than those of other potent stimulators of osteoclastic bone resorption (parathyroid hormone, vitamin D metabolites, osteoclast activating factor, and prostaglandins), but the maximum response was not as great. We conclude that T4 and T3 can directly stimulate bone resorption in vitro at concentrations approaching those which occur in thyrotoxicosis. This effect may explain the disturbances of calcium metabolism seen in hyperthyroidism."} {"id": "PMID:182722", "title": "In vitro behavior of human intestinal mucosa. The influence of acetyl choline on ion transport.", "content": "The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P less than 0.002) and short circuit current (287.7-417.2 muA-cm-2, P less than 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (58) to a net Cl secretion (-4.3mueq-cm-2-h-1P less than 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 mueq-cm-2-h-1P less than 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 mueq-cm-2-h-1P less than 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition. These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by which the parasympathetic nervous system could be concerned in the control of ion transport.", "contents": "In vitro behavior of human intestinal mucosa. The influence of acetyl choline on ion transport. The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P less than 0.002) and short circuit current (287.7-417.2 muA-cm-2, P less than 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (58) to a net Cl secretion (-4.3mueq-cm-2-h-1P less than 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 mueq-cm-2-h-1P less than 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 mueq-cm-2-h-1P less than 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition. These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by which the parasympathetic nervous system could be concerned in the control of ion transport."} {"id": "PMID:182723", "title": "Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.", "content": "Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma \"mineralocorticoid\" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin \"essential\" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.", "contents": "Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states. Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma \"mineralocorticoid\" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin \"essential\" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION."} {"id": "PMID:182724", "title": "Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.", "content": "Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46 +/- 5 A and a mean diameter of 190 +/- 25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I approtein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase.", "contents": "Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver. Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46 +/- 5 A and a mean diameter of 190 +/- 25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I approtein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase."} {"id": "PMID:182731", "title": "Modulation of human T lymphocyte rosette formation by autonomic agonists and cyclic nucleotides.", "content": "Early rosette formation by T lymphocytes appears to be modulated by cyclic nucleotides. Dibutyryl cyclic 3',5' adenosine monophosphate (cyclic AMP) 10(-2) M inhibited E rosette formation up to 83%, while 10(-6) M 8-bromo-cyclic guanosine monophosphate (cyclic GMP) increased rosette formation maximally to 67.4% with less pronounced effect at increased concentrations. T lymphocyte receptors for beta adrenergic, alpha adrenergic, and muscarinic cholinergic agonists appear to influence rosette formation. Isoproternol 10(-2) M induced 67.3% inhibition, while phenylephrine 10(-5) M and carbamylcholine 10(-4) M were associated with enhanced rosette formation of 67.2% and 57.8%, respectively. Selective blockade with propranolol, phentolamine, and atropine indicated the presence of separate receptor sites. The lack of effect of histamine at concentrations of 10(-3) M and above suggests the absence of specific recepotrs on peripheral human T lymphocytes.", "contents": "Modulation of human T lymphocyte rosette formation by autonomic agonists and cyclic nucleotides. Early rosette formation by T lymphocytes appears to be modulated by cyclic nucleotides. Dibutyryl cyclic 3',5' adenosine monophosphate (cyclic AMP) 10(-2) M inhibited E rosette formation up to 83%, while 10(-6) M 8-bromo-cyclic guanosine monophosphate (cyclic GMP) increased rosette formation maximally to 67.4% with less pronounced effect at increased concentrations. T lymphocyte receptors for beta adrenergic, alpha adrenergic, and muscarinic cholinergic agonists appear to influence rosette formation. Isoproternol 10(-2) M induced 67.3% inhibition, while phenylephrine 10(-5) M and carbamylcholine 10(-4) M were associated with enhanced rosette formation of 67.2% and 57.8%, respectively. Selective blockade with propranolol, phentolamine, and atropine indicated the presence of separate receptor sites. The lack of effect of histamine at concentrations of 10(-3) M and above suggests the absence of specific recepotrs on peripheral human T lymphocytes."} {"id": "PMID:182742", "title": "[Ultrastructural and histochemical study of the zones of the junctions of luteal cells in women. Functional significance].", "content": "We are reporting here the results of an electron microscopic study of the junction between cells which have been seen in corpora lutea in human beings between the 20th and 27th days of the cycle. Conventional electron microscopic techniques, using tracers (plotters) for the extracellular spaces as well as Thiery's histochemical technique, were used. Two principal types of junctions between the cells have been described: tight junctions and septate junctions. A discussion takes place about the different histophysiological problems which presented (LH hormone receptors and intercellular diffusion of the message).", "contents": "[Ultrastructural and histochemical study of the zones of the junctions of luteal cells in women. Functional significance]. We are reporting here the results of an electron microscopic study of the junction between cells which have been seen in corpora lutea in human beings between the 20th and 27th days of the cycle. Conventional electron microscopic techniques, using tracers (plotters) for the extracellular spaces as well as Thiery's histochemical technique, were used. Two principal types of junctions between the cells have been described: tight junctions and septate junctions. A discussion takes place about the different histophysiological problems which presented (LH hormone receptors and intercellular diffusion of the message)."} {"id": "PMID:182877", "title": "Preparation of ferritin-avidin conjugates by reductive alkylation for use in electron microscopic cytochemistry.", "content": "An improved technique was developed for the unidirectional covalent binding of avidin to ferritin by reductive alkylation. The method is based on the oxidation of sugar moieties on avidin and subsequent coupling to amino groups of ferritin via Schiff's bases followed by reduction with sodium borohydride. The resultant conjugate was used as an ultrastructural marker for the localization of surface receptor sites on biotin-derivatized whole cells. Erythrocytes were treated chemically with sodium meta-periodate and biotin hydrazide in succession. The ferritin-avidin conjugates were used to label the biotin sites either before or after fixation of the cells. The density and distribution of ferritin avidin conjugates on cell surfaces were anlyzed on thin sections and compared with those of cationized ferritin, which were shown to bind anionic sites of the erythrocyte membrane. The extensions of this method for the visualization of other systems is discussed.", "contents": "Preparation of ferritin-avidin conjugates by reductive alkylation for use in electron microscopic cytochemistry. An improved technique was developed for the unidirectional covalent binding of avidin to ferritin by reductive alkylation. The method is based on the oxidation of sugar moieties on avidin and subsequent coupling to amino groups of ferritin via Schiff's bases followed by reduction with sodium borohydride. The resultant conjugate was used as an ultrastructural marker for the localization of surface receptor sites on biotin-derivatized whole cells. Erythrocytes were treated chemically with sodium meta-periodate and biotin hydrazide in succession. The ferritin-avidin conjugates were used to label the biotin sites either before or after fixation of the cells. The density and distribution of ferritin avidin conjugates on cell surfaces were anlyzed on thin sections and compared with those of cationized ferritin, which were shown to bind anionic sites of the erythrocyte membrane. The extensions of this method for the visualization of other systems is discussed."} {"id": "PMID:182879", "title": "Inhibition of normal mouse lymphocyte mitogen responses by xenogeneic or allogeneic antibodies to the MuLV glycoprotein gp71.", "content": "Xenogeneic and allogeneic antisera to the major envelope glycoprotein (gp71) of murine leukemia viruses (NyLV) inhibited the mitogenic response of normal mouse splenic lymphocytes to phytohemagglutinin (PHA) and lipopolysaccharide (LPS). This inhibition was specific for gp71 as demonstrated by the inability of xenogeneic antisera to other viral glycoproteins or structural proteins to inhibit and by the ability of purified antigens to block specifically the inhibitory effect. The ability of antisera to gp71 to inhibit LPS responses, however, is highly dependent on the strain and age of mouse spleen cells used and appears correlated with the expression of endogenous viruses. Moreover, the preferential inhibition of LPS responses suggests that this expression may be predominately B cell specific. The results suggest that the inhibitory effect is mediated via antibody binding to lymphocytes and that expression of viral envelope antigens on the cell surface which bind immunoglobulins can block or interfere with the binding or uptake of mitogens. A variety of natural mouse immune sera and \"tumor\" sera, having antibodies directed against gp71, can similarly inhibit mitogen responses; and this inhibition can be specifically blocked with MuLV or gp71.", "contents": "Inhibition of normal mouse lymphocyte mitogen responses by xenogeneic or allogeneic antibodies to the MuLV glycoprotein gp71. Xenogeneic and allogeneic antisera to the major envelope glycoprotein (gp71) of murine leukemia viruses (NyLV) inhibited the mitogenic response of normal mouse splenic lymphocytes to phytohemagglutinin (PHA) and lipopolysaccharide (LPS). This inhibition was specific for gp71 as demonstrated by the inability of xenogeneic antisera to other viral glycoproteins or structural proteins to inhibit and by the ability of purified antigens to block specifically the inhibitory effect. The ability of antisera to gp71 to inhibit LPS responses, however, is highly dependent on the strain and age of mouse spleen cells used and appears correlated with the expression of endogenous viruses. Moreover, the preferential inhibition of LPS responses suggests that this expression may be predominately B cell specific. The results suggest that the inhibitory effect is mediated via antibody binding to lymphocytes and that expression of viral envelope antigens on the cell surface which bind immunoglobulins can block or interfere with the binding or uptake of mitogens. A variety of natural mouse immune sera and \"tumor\" sera, having antibodies directed against gp71, can similarly inhibit mitogen responses; and this inhibition can be specifically blocked with MuLV or gp71."} {"id": "PMID:182741", "title": "[Hepatic adenoma and oral contraception].", "content": "The authors report 2 new cases of adenoma of the liver in women who had been taking oral contraceptives. They review the world literature and analyse 18 of the 31 cases so far described. They consider the theoretical and practical problems posed by liver adenomata. As far as the theory goes, they think that uninterrupted taking of the pill for several years may cause the liver to become hyperactive in order to neutralise the excessive and permanent oestro-progesterone hormones brought to it. Following this, the liver gland responds with hypertrophy. As far as the practical aspect goes, the clinician is faced with the problem of supervision and clinical examination of the abdomen of women who take the pill for a ling time. Gynaecologist and the general surgeon have to know that there are complications with this tumour and in particular acute intraperitoneal bleeding.", "contents": "[Hepatic adenoma and oral contraception]. The authors report 2 new cases of adenoma of the liver in women who had been taking oral contraceptives. They review the world literature and analyse 18 of the 31 cases so far described. They consider the theoretical and practical problems posed by liver adenomata. As far as the theory goes, they think that uninterrupted taking of the pill for several years may cause the liver to become hyperactive in order to neutralise the excessive and permanent oestro-progesterone hormones brought to it. Following this, the liver gland responds with hypertrophy. As far as the practical aspect goes, the clinician is faced with the problem of supervision and clinical examination of the abdomen of women who take the pill for a ling time. Gynaecologist and the general surgeon have to know that there are complications with this tumour and in particular acute intraperitoneal bleeding."} {"id": "PMID:182880", "title": "The kinetics of interferon production by mouse lymphocytes and its modulating effect of the virus plaqueforming cell assay as a quantitative method to determine activated lymphocytes.", "content": "The validity of the virus plaque-forming cell (V-PFC) assay as a means to quantitate stimulated mouse T cells is dependent on the rate and amount of coinciding interferon production which varies with different strains of mice. In addition, the V-PFC assay demonstrates that the kinetics of cellular activation by mitogens initially involves about 0.01% of responding cells and possibly recruitment of other cells which include cells requiring a longer lap period for activation.", "contents": "The kinetics of interferon production by mouse lymphocytes and its modulating effect of the virus plaqueforming cell assay as a quantitative method to determine activated lymphocytes. The validity of the virus plaque-forming cell (V-PFC) assay as a means to quantitate stimulated mouse T cells is dependent on the rate and amount of coinciding interferon production which varies with different strains of mice. In addition, the V-PFC assay demonstrates that the kinetics of cellular activation by mitogens initially involves about 0.01% of responding cells and possibly recruitment of other cells which include cells requiring a longer lap period for activation."} {"id": "PMID:182881", "title": "The role of circulating interferon in the modifications of immune responsiveness by mouse hepatitis virus (MHV-3).", "content": "MHV-3 modifies the humoral immune response to SRBC. During acute infections timing was critical: infecting mice before antigen administration led to immunodepression. Simultaneous injection with virus and SRBC resulted in immunostimulation. Persistent MHV-3 infections were associated with a chronic immunodepression. The presence of circulating interferon (IF) was well correlated with these modifications. IF peaking before antigen was associated with immunodepression whereas IF secretion after antigen was associated with immunostimulation. Low, permanent levels of IF were associated with chronic immunodepression. Since IF is, up to now, the only product of activated lymphocytes that has been shown to modulate immune responses, our results suggest that induction of IF by MHV-3 may be the main mechanism by which this virus modifies immune responsiveness. Moreover, we have shown that MHV-3 infection in susceptible mice diminishes the secretion of lymphocyte IF in response to Sendai virus. In these animals, the thymus cortex was profoundly depleted although the thymus medulla remained unchanged. The MHV-3 infection may, therefore, interfere with a subpopulation of IF-secreting lymphocytes. The possible physiologic role of such lymphocyte subpopulation in terms of host-virus relationships is discussed.", "contents": "The role of circulating interferon in the modifications of immune responsiveness by mouse hepatitis virus (MHV-3). MHV-3 modifies the humoral immune response to SRBC. During acute infections timing was critical: infecting mice before antigen administration led to immunodepression. Simultaneous injection with virus and SRBC resulted in immunostimulation. Persistent MHV-3 infections were associated with a chronic immunodepression. The presence of circulating interferon (IF) was well correlated with these modifications. IF peaking before antigen was associated with immunodepression whereas IF secretion after antigen was associated with immunostimulation. Low, permanent levels of IF were associated with chronic immunodepression. Since IF is, up to now, the only product of activated lymphocytes that has been shown to modulate immune responses, our results suggest that induction of IF by MHV-3 may be the main mechanism by which this virus modifies immune responsiveness. Moreover, we have shown that MHV-3 infection in susceptible mice diminishes the secretion of lymphocyte IF in response to Sendai virus. In these animals, the thymus cortex was profoundly depleted although the thymus medulla remained unchanged. The MHV-3 infection may, therefore, interfere with a subpopulation of IF-secreting lymphocytes. The possible physiologic role of such lymphocyte subpopulation in terms of host-virus relationships is discussed."} {"id": "PMID:182882", "title": "Hepatitis A antigen isolated from liver and stool: immunologic comparison of antisera prepared in guinea pigs.", "content": "Morphologically similar hepatitis A antigen particles (HA Ag)3 have been detected in the stools of patients with type A hepatitis and in the livers of marmosets experimentally infected with hepatitis A virus. To investigate the humoral antibody responses to these antigens and to compare the immunologic properties of HA Ag from these two sources, we immunized guinea pigs with either marmoset liver-derived HA Ag or with human stool-derived HA Ag in complete Freund's adjuvant and measured their antibody responses by immune electron microscopy (IEM) and immune adherence hemagglutination (IAHA). Antibodies reacting with both hepatitis A antigens were elicited in both groups. As determined by IEM, no distinction was seen between the reaction of guinea pig antiserum to each HA Ag tested under code when reacted against either liver-derived or stool-derived HA Ag. Antibodies elicited to marmoset liver-derived HA Ag and human stool-derived HA Ag had similar end point dilution titers by IAHA when tested against either \"light\" density (1.34 g/cm3) or \"heavy\" density (1.40 g/cm3) stool-derived HA Ag or liver-derived HA Ag. Low levels of antibody to normal liver or stool control antigens were observed transiently but did not obscure the specific response to HA Ag. These data suggest that morphologically similar HA Ag particles from different sources and with different densities are immunologically similar and may be identical. In contrast to the heterogeneity of surface antigens of hepatitis B virus, the comparable immunogenicity and apparent antigenic homogeneity of HA Ags derived from various sources may simplify the approach to development of a vaccine against viral hepatitis, type A.", "contents": "Hepatitis A antigen isolated from liver and stool: immunologic comparison of antisera prepared in guinea pigs. Morphologically similar hepatitis A antigen particles (HA Ag)3 have been detected in the stools of patients with type A hepatitis and in the livers of marmosets experimentally infected with hepatitis A virus. To investigate the humoral antibody responses to these antigens and to compare the immunologic properties of HA Ag from these two sources, we immunized guinea pigs with either marmoset liver-derived HA Ag or with human stool-derived HA Ag in complete Freund's adjuvant and measured their antibody responses by immune electron microscopy (IEM) and immune adherence hemagglutination (IAHA). Antibodies reacting with both hepatitis A antigens were elicited in both groups. As determined by IEM, no distinction was seen between the reaction of guinea pig antiserum to each HA Ag tested under code when reacted against either liver-derived or stool-derived HA Ag. Antibodies elicited to marmoset liver-derived HA Ag and human stool-derived HA Ag had similar end point dilution titers by IAHA when tested against either \"light\" density (1.34 g/cm3) or \"heavy\" density (1.40 g/cm3) stool-derived HA Ag or liver-derived HA Ag. Low levels of antibody to normal liver or stool control antigens were observed transiently but did not obscure the specific response to HA Ag. These data suggest that morphologically similar HA Ag particles from different sources and with different densities are immunologically similar and may be identical. In contrast to the heterogeneity of surface antigens of hepatitis B virus, the comparable immunogenicity and apparent antigenic homogeneity of HA Ags derived from various sources may simplify the approach to development of a vaccine against viral hepatitis, type A."} {"id": "PMID:182883", "title": "Herpes simplex-RAJI(A44), a new cell line for serologic testing by immunofluorescence.", "content": "An IF technique for the detection of HSV antibodies by using a lymphoblastoid cell line, Raji(A44), which continuously produce a constant amount of HSV antigen, is described. IF and IH tests were found to be similar with respect to sensitivity and reproducibility. Sero-conversions detected by the CF test were detected with this cell line. The Raji(A44) line (cells in suspension) can be routinely used for the diagnosis of HSV infection.", "contents": "Herpes simplex-RAJI(A44), a new cell line for serologic testing by immunofluorescence. An IF technique for the detection of HSV antibodies by using a lymphoblastoid cell line, Raji(A44), which continuously produce a constant amount of HSV antigen, is described. IF and IH tests were found to be similar with respect to sensitivity and reproducibility. Sero-conversions detected by the CF test were detected with this cell line. The Raji(A44) line (cells in suspension) can be routinely used for the diagnosis of HSV infection."} {"id": "PMID:182884", "title": "Studies on the specificity of in vitro induced lymphocytotoxicity to SV40-transformed fibroblasts.", "content": "Cytotoxic effector lymphocytes were induced by in vitro immunization of lymph node and spleen cells from AKR-mice (H-2k) and from BALB/c-mice (H-2d) to syngeneic SV40-transformed fibroblasts. The T cell-dependent cytotoxicity was specific for target cells expressing the same H2-specificity as the immunizing cells. Nontransformed fibroblasts as stimulator cells did not induce efficient cytotoxicity to transformed or nontransformed target cells. Incubation with phytohemagglutinin during the sensitization period modified the specificity of the T cell-mediated lysis of syngeneic SV40-transformed fibroblasts: allogeneic as well as syngeneic target cells were destroyed by these effector cells. However, the polyclonal stimulant activates preferentially cytotoxicity to H2-matched target cells. The in vitro generation of cytotoxic effector cells was restricted to living SV40-transformed fibroblasts as immunizing cells; it was not possible to immunize lymphocytes in the presence of membrane proteins prepared from the SV40-transformed cells. The cytotoxicity of the in vitro immunized lymphocytes was inhibited by incubation with membrane protein preparations from syngeneic or allogeneic SV40-transformed fibroblasts.", "contents": "Studies on the specificity of in vitro induced lymphocytotoxicity to SV40-transformed fibroblasts. Cytotoxic effector lymphocytes were induced by in vitro immunization of lymph node and spleen cells from AKR-mice (H-2k) and from BALB/c-mice (H-2d) to syngeneic SV40-transformed fibroblasts. The T cell-dependent cytotoxicity was specific for target cells expressing the same H2-specificity as the immunizing cells. Nontransformed fibroblasts as stimulator cells did not induce efficient cytotoxicity to transformed or nontransformed target cells. Incubation with phytohemagglutinin during the sensitization period modified the specificity of the T cell-mediated lysis of syngeneic SV40-transformed fibroblasts: allogeneic as well as syngeneic target cells were destroyed by these effector cells. However, the polyclonal stimulant activates preferentially cytotoxicity to H2-matched target cells. The in vitro generation of cytotoxic effector cells was restricted to living SV40-transformed fibroblasts as immunizing cells; it was not possible to immunize lymphocytes in the presence of membrane proteins prepared from the SV40-transformed cells. The cytotoxicity of the in vitro immunized lymphocytes was inhibited by incubation with membrane protein preparations from syngeneic or allogeneic SV40-transformed fibroblasts."} {"id": "PMID:182885", "title": "Radioimmunoassay for herpes simplex virus.", "content": "Radioimmunoassay has been used for time in the detection of the Australia Antigen. In this experiment, radioimmunoassay with Iodine-125 (125I) permitted rapid detection of the presence of herpes simplex virus, type I, in vitro. This is a convenient technique for the detection of virus, which now requires laborious methods involving observation for the cytopathic effect of virus upon cultured cells.", "contents": "Radioimmunoassay for herpes simplex virus. Radioimmunoassay has been used for time in the detection of the Australia Antigen. In this experiment, radioimmunoassay with Iodine-125 (125I) permitted rapid detection of the presence of herpes simplex virus, type I, in vitro. This is a convenient technique for the detection of virus, which now requires laborious methods involving observation for the cytopathic effect of virus upon cultured cells."} {"id": "PMID:182887", "title": "Polymorphonuclear leukocyte inclusions and impaired bacterial killing in patients with Felty's syndrome.", "content": "Humoral factors, phagocytosis, bactericidal capability, and ultrastructural morphology of blood polymorphonuclear leukocytes were investigated in 10 patients with Felty's syndrome. Five patients had suffered significant bacterial infections in the past two years while five other patients had not had bacterial infections. The patients with infections had higher concentrations of serum cryoglobulins, and their neutrophils contained immunoglobulin inclusions as seen by immunofluorescent and electron microscopy. Additionally, leukocytes from these patients showed decreased ability to kill Staphylococcus aureus and a minor defect in phagocytosis. There was a generalized subcellular disorganization of these inclusion containing neutrophils and a slower than normal release of lysosomes. Several of the above abnormalities may contribute to an increased susceptibility to bacterial infections in patients with Felty's syndrome.", "contents": "Polymorphonuclear leukocyte inclusions and impaired bacterial killing in patients with Felty's syndrome. Humoral factors, phagocytosis, bactericidal capability, and ultrastructural morphology of blood polymorphonuclear leukocytes were investigated in 10 patients with Felty's syndrome. Five patients had suffered significant bacterial infections in the past two years while five other patients had not had bacterial infections. The patients with infections had higher concentrations of serum cryoglobulins, and their neutrophils contained immunoglobulin inclusions as seen by immunofluorescent and electron microscopy. Additionally, leukocytes from these patients showed decreased ability to kill Staphylococcus aureus and a minor defect in phagocytosis. There was a generalized subcellular disorganization of these inclusion containing neutrophils and a slower than normal release of lysosomes. Several of the above abnormalities may contribute to an increased susceptibility to bacterial infections in patients with Felty's syndrome."} {"id": "PMID:182888", "title": "Abnormalities of cholesterol turnover in hypercholesterolemic (type II) patients.", "content": "Cholesterol turnover was measured in 5 normal subjects and 14 familial hypercholesterolemic (Type II) patients. All patients were fed eucaloric cholesterol-free or very low cholesterol formula or mixed-food diets. They were given single doses of cholesterol-1,2-3H and cholesterol-4-14C simultaneously, one isotope intravenously (IV), and the other orally. Plasma cholesterol specific radioactivity decay curves for 3H and 14C isotopes in each patient conformed to the short-term (10 to 12 weeks) kinetics of the two-pool model. In type II patients, the total mass of cholesterol in pool A was significantly larger by about 17 Gm. (by the IV method) and 27 Gm. (by the oral method) as compared with normal subjects. The increase in size of pool A in Type II patients occurred equally in plasma and tissues comprising pool A (probably liver and intestine). The rate constant for the excretion of cholesterol from pool A was significantly reduced in the Type II patients. The rate constant for the transfer of cholesterol from pool A to pool B was also reduced in the Type II patients. Furthermore, the metabolic clearance fraction was decreased by 50 per cent as compared with normal subjects. In normal subjects and in Type II patients, the size of pool A was significantly larger by about 5 Gm. and 15 Gm., respectively, by the oral method as compared with the IV method. This difference in the size of pool A probably reflects differences in isotopic equilibration with the intestinal mucosal cholesterol pool. All other parameters of cholesterol turnover by the IV method as compared with the oral method were similar. Our results suggest that the expanded rapidly exchangeable pool of cholesterol (pool A) is due to a defect in cholesterol transport and excretion in familial hypercholesterolemia (Type II). The decreased rate of removal of cholesterol from the plasma and/or catabolism in tissues could be one important cause of familial hypercholesterolemia in man.", "contents": "Abnormalities of cholesterol turnover in hypercholesterolemic (type II) patients. Cholesterol turnover was measured in 5 normal subjects and 14 familial hypercholesterolemic (Type II) patients. All patients were fed eucaloric cholesterol-free or very low cholesterol formula or mixed-food diets. They were given single doses of cholesterol-1,2-3H and cholesterol-4-14C simultaneously, one isotope intravenously (IV), and the other orally. Plasma cholesterol specific radioactivity decay curves for 3H and 14C isotopes in each patient conformed to the short-term (10 to 12 weeks) kinetics of the two-pool model. In type II patients, the total mass of cholesterol in pool A was significantly larger by about 17 Gm. (by the IV method) and 27 Gm. (by the oral method) as compared with normal subjects. The increase in size of pool A in Type II patients occurred equally in plasma and tissues comprising pool A (probably liver and intestine). The rate constant for the excretion of cholesterol from pool A was significantly reduced in the Type II patients. The rate constant for the transfer of cholesterol from pool A to pool B was also reduced in the Type II patients. Furthermore, the metabolic clearance fraction was decreased by 50 per cent as compared with normal subjects. In normal subjects and in Type II patients, the size of pool A was significantly larger by about 5 Gm. and 15 Gm., respectively, by the oral method as compared with the IV method. This difference in the size of pool A probably reflects differences in isotopic equilibration with the intestinal mucosal cholesterol pool. All other parameters of cholesterol turnover by the IV method as compared with the oral method were similar. Our results suggest that the expanded rapidly exchangeable pool of cholesterol (pool A) is due to a defect in cholesterol transport and excretion in familial hypercholesterolemia (Type II). The decreased rate of removal of cholesterol from the plasma and/or catabolism in tissues could be one important cause of familial hypercholesterolemia in man."} {"id": "PMID:182889", "title": "Effect of cyclic 3',5'-guanosine monophosphate on human platelet function.", "content": "The relation of cyclic 3',5'-guanosine monophosphate (cGMP) to platelet function was studied by investigating the influence of this compound and its N2,O2'-dibutyryl derivative (DBcGMP) on platelet aggregation and the release reaction. Both cGMP and dibutyryl cGMP enhanced to an equal extent platelet aggregation induced by epinephrine or by chick skin collagen alpha1 chain. The platelet release reaction, as measured by the release of [14C]-labeled 5-hydroxytryptamine (serotonin) was also enhanced by the cyclic nucleotides. Both compounds were also able to partially overcome the inhibitory effect of N6,O2'-dibutyryl 3',5'-adenosine monophosphate (DBcAMP), prostaglandin E1, and theophylline. The effect of DBcGMP did not result from contamination with 5'-GMP. Butyric acid and 5'-GMP, either alone or in combination, had no detectable effect on platelet function. The in vitro effect of DBcGMP and cGMP was not dependent on preincubation of platelets with the compounds. This suggests that their effect is mediated by direct action on the platelet membranes. These data are consistent with previous observations that the platelet aggregating agents (epinephrine, ADP, collagen, and chick collagen alpha1 chains) cause an increase in the content of GMP, and support the hypothesis that platelet aggregation is favored by an increase in cGMP.", "contents": "Effect of cyclic 3',5'-guanosine monophosphate on human platelet function. The relation of cyclic 3',5'-guanosine monophosphate (cGMP) to platelet function was studied by investigating the influence of this compound and its N2,O2'-dibutyryl derivative (DBcGMP) on platelet aggregation and the release reaction. Both cGMP and dibutyryl cGMP enhanced to an equal extent platelet aggregation induced by epinephrine or by chick skin collagen alpha1 chain. The platelet release reaction, as measured by the release of [14C]-labeled 5-hydroxytryptamine (serotonin) was also enhanced by the cyclic nucleotides. Both compounds were also able to partially overcome the inhibitory effect of N6,O2'-dibutyryl 3',5'-adenosine monophosphate (DBcAMP), prostaglandin E1, and theophylline. The effect of DBcGMP did not result from contamination with 5'-GMP. Butyric acid and 5'-GMP, either alone or in combination, had no detectable effect on platelet function. The in vitro effect of DBcGMP and cGMP was not dependent on preincubation of platelets with the compounds. This suggests that their effect is mediated by direct action on the platelet membranes. These data are consistent with previous observations that the platelet aggregating agents (epinephrine, ADP, collagen, and chick collagen alpha1 chains) cause an increase in the content of GMP, and support the hypothesis that platelet aggregation is favored by an increase in cGMP."} {"id": "PMID:182890", "title": "The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism.", "content": "The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus.", "contents": "The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism. The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus."} {"id": "PMID:182891", "title": "Mathematical evaluation of methods for estimation of the concentration of the major lipid components of human serum lipoproteins.", "content": "The concentration of total cholesterol and triglycerides in the three major lipoprotein classes of human serum was measured in 136 men, randomly selected from an industrial population, by a quantitative method of lipoprotein electrophoresis on agarose gel and of fractions separated by preparative ultracentrifugation. Correlation coefficients for the two estimates were 0.98 for triglycerides in very low-density lipoproteins, 0.93 for total cholesterol in low-density lipoproteins, and 0.75 for total cholesterol in high-density lipoproteins. Data obtained form the analyses of the ultracentrifugal fractions were used to develop regression equations that predict the concentrations of total cholesterol and triglycerides in the lipoprotein classes from their concentrations in whole serum. These equations take into account the inverse curvilinear relationship between total cholesterol in high-density lipoproteins and serum tiriglyceride concentration. When applied to a separate sample of 530 men, the predicted values for triglycerides in very low-density lipoproteins and total cholesterol in low-density lipoproteins correlated as well with ultracentrifugal values as did the electrophoretic estimates. However, for total cholesterol in high-density lipoproteins, the electrophoretic method was superior. Similar regression equations were developed from ultracentrifugal lipoprotein analyses in 158 women from the same industrial population. Although the concentration of total cholesterol in the low-density lipoproteins estimated by both electrophoresis and the regression equations agreed closely in most cases with the ultracentrifugal values, errors exceeded 10% with sufficient frequency to limit the value of the estimates for this purpose. In both men and women, the ratio of total cholesterol to triglycerides in high-density lipoproteins was a hyperbolic function of serum triglyceride concentration, suggesting that cholesteryl esters in the core of this lipoprotein are progressively replaced by triglycerides as the concentration of triglycerides in very low-density lipoproteins increases. This altered composition of nonpolar lipids accounts, at least in part, for the reduction of cholesterol in high-density lipoproteins in hyperlipemic individuals.", "contents": "Mathematical evaluation of methods for estimation of the concentration of the major lipid components of human serum lipoproteins. The concentration of total cholesterol and triglycerides in the three major lipoprotein classes of human serum was measured in 136 men, randomly selected from an industrial population, by a quantitative method of lipoprotein electrophoresis on agarose gel and of fractions separated by preparative ultracentrifugation. Correlation coefficients for the two estimates were 0.98 for triglycerides in very low-density lipoproteins, 0.93 for total cholesterol in low-density lipoproteins, and 0.75 for total cholesterol in high-density lipoproteins. Data obtained form the analyses of the ultracentrifugal fractions were used to develop regression equations that predict the concentrations of total cholesterol and triglycerides in the lipoprotein classes from their concentrations in whole serum. These equations take into account the inverse curvilinear relationship between total cholesterol in high-density lipoproteins and serum tiriglyceride concentration. When applied to a separate sample of 530 men, the predicted values for triglycerides in very low-density lipoproteins and total cholesterol in low-density lipoproteins correlated as well with ultracentrifugal values as did the electrophoretic estimates. However, for total cholesterol in high-density lipoproteins, the electrophoretic method was superior. Similar regression equations were developed from ultracentrifugal lipoprotein analyses in 158 women from the same industrial population. Although the concentration of total cholesterol in the low-density lipoproteins estimated by both electrophoresis and the regression equations agreed closely in most cases with the ultracentrifugal values, errors exceeded 10% with sufficient frequency to limit the value of the estimates for this purpose. In both men and women, the ratio of total cholesterol to triglycerides in high-density lipoproteins was a hyperbolic function of serum triglyceride concentration, suggesting that cholesteryl esters in the core of this lipoprotein are progressively replaced by triglycerides as the concentration of triglycerides in very low-density lipoproteins increases. This altered composition of nonpolar lipids accounts, at least in part, for the reduction of cholesterol in high-density lipoproteins in hyperlipemic individuals."} {"id": "PMID:182892", "title": "Radiotherapy in carcinoma of the middle ear and auditory canal.", "content": "In the decade 1961 to 1970, 89 patients with epidermoid carcinoma of the middle ear or auditory canal were seen. Seventy-eight were treated with 5-year survival figures of 22 per cent for middle ear, 42 per cent for auditory canal and 31 per cent for the total group. The majority of failures occurred within 18 months of diagnosis. The author suggests that radiotherapy and surgery must be combined to improve results. Eleven patients in the series developed second primary tumours.", "contents": "Radiotherapy in carcinoma of the middle ear and auditory canal. In the decade 1961 to 1970, 89 patients with epidermoid carcinoma of the middle ear or auditory canal were seen. Seventy-eight were treated with 5-year survival figures of 22 per cent for middle ear, 42 per cent for auditory canal and 31 per cent for the total group. The majority of failures occurred within 18 months of diagnosis. The author suggests that radiotherapy and surgery must be combined to improve results. Eleven patients in the series developed second primary tumours."} {"id": "PMID:182894", "title": "Binding, internalization, and hydrolysis of low density lipoprotein in long-term lymphoid cell lines from a normal subject and a patient with homozygous familial hypercholesterolemia.", "content": "Long-term established human lymphoid cells were shown to possess high affinity cell surface receptors for low density lipoprotein (LDL), the major cholesterol-carrying protein in human plasma. Binding of LDL to these receptors was followed by internalization of the lipoprotein and hydrolysis of its protein and cholesteryl ester components. Cultured lymphocytes from a patient with the homozygous form of familial hypercholesterolemia lacked cell surface LDL receptors and therefore failed to take up and degrade the lipoprotein with high affinity. Cultured human lymphocytes should prove useful for further studies of: (a) the relation between cholesterol metabolism and cellular function and (b) the mechanism by which LDL binding at the cell surface leads to internalization of the lipoprotein.", "contents": "Binding, internalization, and hydrolysis of low density lipoprotein in long-term lymphoid cell lines from a normal subject and a patient with homozygous familial hypercholesterolemia. Long-term established human lymphoid cells were shown to possess high affinity cell surface receptors for low density lipoprotein (LDL), the major cholesterol-carrying protein in human plasma. Binding of LDL to these receptors was followed by internalization of the lipoprotein and hydrolysis of its protein and cholesteryl ester components. Cultured lymphocytes from a patient with the homozygous form of familial hypercholesterolemia lacked cell surface LDL receptors and therefore failed to take up and degrade the lipoprotein with high affinity. Cultured human lymphocytes should prove useful for further studies of: (a) the relation between cholesterol metabolism and cellular function and (b) the mechanism by which LDL binding at the cell surface leads to internalization of the lipoprotein."} {"id": "PMID:182895", "title": "Spontaneous autoimmunization to GIX cell surface antigen in hybrid mice.", "content": "The GIX antigen expressed on the thymocytes of GIX+ mice is a type-specific constituent of glycoprotein gp70, which forms the major envelope component of murine leukemia virus. In the prototype GIX+ mouse strain 129, this glycoprotein is a Mendelian character expressed independently of virus production. In the intact thymocyte plasma membrane, part of this glycoprotein, bearing group-specific (gs) antigen, is inaccessible to antibody. The moiety bearing the type-specific GIX determinant is accessible to GIX antibody, which may be an important factor in determining the consequences of autoimmune responses involving GIX. Previously, all attempts to induce GIX antibody in mice had failed. We now find that the hybrid mouse (B6-GIX+ X 129) spontaneously produces substantial amounts of GIX antibody, presumably of the IgM class appearing as early as 2 mo of age. The specificity of the GIX natural mouse antibody is the same as that recognized by the conventional GIX typing serum produced in rats (\"anti-NTD\"). As neither parent strain produces appreciable GIX antibody, we surmise that this autoimmune response requires two dominant genes, each parent contributing a high-response allele to the hybrid. These can be envisaged as two immune response loci, controlling different immunocompetent cells which must cooperate to produce GIX antibody. Production of GIX antibody by the hybrids increases progressively with age. This is accompanied by decreased expression of GIX antigen on their thymocytes. We attribute this to antigenic modulation. Antibody to gs antigen of gp70 is also found in autoimmune (B6-GIX+ X 129) hybrids but not in either parent strain. We are investigating evidence of a pathological autoimmune syndrome in these hybrids. The special interest of this syndrome is that it presumably signifies the consequences of autoimmunization to a single C-type virus component, expressed without significant virus production, in a mouse with no evident genetic predisposition to such disease in the absence of that antigen.", "contents": "Spontaneous autoimmunization to GIX cell surface antigen in hybrid mice. The GIX antigen expressed on the thymocytes of GIX+ mice is a type-specific constituent of glycoprotein gp70, which forms the major envelope component of murine leukemia virus. In the prototype GIX+ mouse strain 129, this glycoprotein is a Mendelian character expressed independently of virus production. In the intact thymocyte plasma membrane, part of this glycoprotein, bearing group-specific (gs) antigen, is inaccessible to antibody. The moiety bearing the type-specific GIX determinant is accessible to GIX antibody, which may be an important factor in determining the consequences of autoimmune responses involving GIX. Previously, all attempts to induce GIX antibody in mice had failed. We now find that the hybrid mouse (B6-GIX+ X 129) spontaneously produces substantial amounts of GIX antibody, presumably of the IgM class appearing as early as 2 mo of age. The specificity of the GIX natural mouse antibody is the same as that recognized by the conventional GIX typing serum produced in rats (\"anti-NTD\"). As neither parent strain produces appreciable GIX antibody, we surmise that this autoimmune response requires two dominant genes, each parent contributing a high-response allele to the hybrid. These can be envisaged as two immune response loci, controlling different immunocompetent cells which must cooperate to produce GIX antibody. Production of GIX antibody by the hybrids increases progressively with age. This is accompanied by decreased expression of GIX antigen on their thymocytes. We attribute this to antigenic modulation. Antibody to gs antigen of gp70 is also found in autoimmune (B6-GIX+ X 129) hybrids but not in either parent strain. We are investigating evidence of a pathological autoimmune syndrome in these hybrids. The special interest of this syndrome is that it presumably signifies the consequences of autoimmunization to a single C-type virus component, expressed without significant virus production, in a mouse with no evident genetic predisposition to such disease in the absence of that antigen."} {"id": "PMID:182896", "title": "Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis.", "content": "Immunization of Lewis rats with acetylcholine receptor (AChR) purified from either Electrophorus electricus electric organ or syngeneic rat muscle induced experimental autoimmune myasthenia gravis (EAMG). This was demonstrated by clinical signs of weakness and by electromyographic evidence of imparied neuromuscular transmission. The amount of rat AChR required to induce an autoimmune response was comparable to the amount of eel AChR required. In vitro complexing of rat AChrR with antibody reduced its immunogenicity. Autoantibody to muscle AChR was present in serum and complexed with AChR in muscle. Antibody was not bound to the ACh binding site of AChR, since antibody-AChR complexes extracted from muscle could still bind 125I-alpha-bungarotoxin. The amount of AChR extracted from muscle of rats with EAMG was diminished. The amount of AChR and antibody-AChR complexes in muscle was measured at intervals after immunization with eel AChR. The amount of AChR decreased in rats with acute EAMG, then transiently increased to more than normal amounts during remission, and finally decreased to only about 20% of normal in rats with chronic EAMG. At least half of the AChR remaining in animals with chronic EAMG was complexed with antibody. Thus, both a decrease in amount of AChR and the formation of antibody-AChR complexes contribute to impairment of neuromuscular transmission in rats with EAMG. The possible mechanisms involved in the changes in AChR content are discussed.", "contents": "Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis. Immunization of Lewis rats with acetylcholine receptor (AChR) purified from either Electrophorus electricus electric organ or syngeneic rat muscle induced experimental autoimmune myasthenia gravis (EAMG). This was demonstrated by clinical signs of weakness and by electromyographic evidence of imparied neuromuscular transmission. The amount of rat AChR required to induce an autoimmune response was comparable to the amount of eel AChR required. In vitro complexing of rat AChrR with antibody reduced its immunogenicity. Autoantibody to muscle AChR was present in serum and complexed with AChR in muscle. Antibody was not bound to the ACh binding site of AChR, since antibody-AChR complexes extracted from muscle could still bind 125I-alpha-bungarotoxin. The amount of AChR extracted from muscle of rats with EAMG was diminished. The amount of AChR and antibody-AChR complexes in muscle was measured at intervals after immunization with eel AChR. The amount of AChR decreased in rats with acute EAMG, then transiently increased to more than normal amounts during remission, and finally decreased to only about 20% of normal in rats with chronic EAMG. At least half of the AChR remaining in animals with chronic EAMG was complexed with antibody. Thus, both a decrease in amount of AChR and the formation of antibody-AChR complexes contribute to impairment of neuromuscular transmission in rats with EAMG. The possible mechanisms involved in the changes in AChR content are discussed."} {"id": "PMID:182897", "title": "Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies.", "content": "Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.", "contents": "Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG."} {"id": "PMID:182898", "title": "Suppression of the antistreptolysin O response by cholesterol and by lipid extracts of rabbit skin.", "content": "Lipids extracted from rabbit skin block the hemolytic capacity of SO and also suppress the neutralizing antibody response to this streptococcal extracellular antigen in rabbith immunized intravenosly. The modification in antibody response is specific for SO; the antibody responses to streptococcal DNase B and to streptococcal NADase are not affected. Cholesterol, a lipid present in abundance in skin, has a similar specific effect on the antigenicity of SO and may be the component responsible for the demonstrated effects of these lipid extracts of skin. In vitro experiments indicate that lipid extracts of rabbit skin have a greater capacity to block the hemolytic capacity of SO than do lipid extracts of rabbit heart, kidney, lung, liver, or spleen. These data support the view that the feeble ASO response observed in patients with streptococcal pyoderma is a result of the abundance of a local lipid inhibitor, such as cholesterol, in the skin. They may also bear on the pathogenesis of rheumatic fever, a complication which apparently does not occur following group A streptococcal pyoderma. Two possible explanations for this remarkable epidemiologic observation, both related to the presence of a local inhibitor, are considered: (a) suppression of the ASO response, the magnitude of which has been correlated with the risk of developing rheumatic fever after streptococcal infection of the throat, and (b) inhibition of the toxicity of SO, which has been shown to have a direct toxic effect on the mammalian heart and on isolated beating myocytes.", "contents": "Suppression of the antistreptolysin O response by cholesterol and by lipid extracts of rabbit skin. Lipids extracted from rabbit skin block the hemolytic capacity of SO and also suppress the neutralizing antibody response to this streptococcal extracellular antigen in rabbith immunized intravenosly. The modification in antibody response is specific for SO; the antibody responses to streptococcal DNase B and to streptococcal NADase are not affected. Cholesterol, a lipid present in abundance in skin, has a similar specific effect on the antigenicity of SO and may be the component responsible for the demonstrated effects of these lipid extracts of skin. In vitro experiments indicate that lipid extracts of rabbit skin have a greater capacity to block the hemolytic capacity of SO than do lipid extracts of rabbit heart, kidney, lung, liver, or spleen. These data support the view that the feeble ASO response observed in patients with streptococcal pyoderma is a result of the abundance of a local lipid inhibitor, such as cholesterol, in the skin. They may also bear on the pathogenesis of rheumatic fever, a complication which apparently does not occur following group A streptococcal pyoderma. Two possible explanations for this remarkable epidemiologic observation, both related to the presence of a local inhibitor, are considered: (a) suppression of the ASO response, the magnitude of which has been correlated with the risk of developing rheumatic fever after streptococcal infection of the throat, and (b) inhibition of the toxicity of SO, which has been shown to have a direct toxic effect on the mammalian heart and on isolated beating myocytes."} {"id": "PMID:182899", "title": "Fc receptor-mediated inhibition of murine B-lymphocyte activation.", "content": "Immobilized antigen-antibody complexes are able to inhibit the mitogenic response of murine spleen cells to the B-cell mitogen 8-bromo-3',5'-cyclic guanosine monophosphoric acid. This this inhibition is dependent on intact Fc fragments in the immobilized complexes. Soluble complexes do not mediate this inhibition. When lipopolysaccharide (lps) activation of B cells was studied, it was found that the mitogenic response was inhibited at all times tested between 2 and 7 days of culture. Also, the LPS-induced mitogenesis of nude spleen cells was inhibited by immobilized complexes, indicating that suppressor T cells probably play no significant role in the inhibition. Immobilized complexes inhibit polyclonal antibody responses in a serum-free system and in the presence of normal mouse serum, but are unable to inhibit in the presence of fetal calf serum (FCS). If nu/nu spleen cells are used, however, the FCS does not block the ability of the complexes to inhibit the polyclonal response. It is suggested that that antigen-antibody complexes under appropriate conditions may bind to B lymphocytes via their Fc receptors and trigger a central \"off\" signal which blocks proliferation and consequently antibody production.", "contents": "Fc receptor-mediated inhibition of murine B-lymphocyte activation. Immobilized antigen-antibody complexes are able to inhibit the mitogenic response of murine spleen cells to the B-cell mitogen 8-bromo-3',5'-cyclic guanosine monophosphoric acid. This this inhibition is dependent on intact Fc fragments in the immobilized complexes. Soluble complexes do not mediate this inhibition. When lipopolysaccharide (lps) activation of B cells was studied, it was found that the mitogenic response was inhibited at all times tested between 2 and 7 days of culture. Also, the LPS-induced mitogenesis of nude spleen cells was inhibited by immobilized complexes, indicating that suppressor T cells probably play no significant role in the inhibition. Immobilized complexes inhibit polyclonal antibody responses in a serum-free system and in the presence of normal mouse serum, but are unable to inhibit in the presence of fetal calf serum (FCS). If nu/nu spleen cells are used, however, the FCS does not block the ability of the complexes to inhibit the polyclonal response. It is suggested that that antigen-antibody complexes under appropriate conditions may bind to B lymphocytes via their Fc receptors and trigger a central \"off\" signal which blocks proliferation and consequently antibody production."} {"id": "PMID:182900", "title": "Isolation of a lipid A bound polypeptide responsible for \"LPS-initiated\" mitogenesis of C3H/HeJ spleen cells.", "content": "The experiments by Sultzer and Nilsson (1), and later by Watson and Riblet (2), established that spleen cells from the C3H/HeJ strain of mouse were refractory to the mitogenic effects of bacterial lipopolysaccharides (LPS). More recently, however, experiments from our laboratory (3) demonstrated that spleen cells from C3H/HeJ mice were in fact responsive to some preparations of LPS but not to others, and that the method of extraction played a critical role in determining activity. In particular, preparations of LPS prepared by extraction with aqueous butanol had potent mitogenic activity. Our data showed that the mitogenic activity of such positive preparations of LPS coisolated with the LPS during gel filtration chromatography and subsequent equilibrium banding on CsCl. In addition, lipid A isolated from positive preparations of LPS was also capable of stimulating C3H/HeJ spleen cells. Taken together, these experiments provided rather convincing data that it was the LPS (in particular the lipid A) itself, or some contaminant very tightly bound to the lipid A, which was responsible for its biological activity. We further demonstrated that treatment of positive preparations of LPS with hot phenol rendered such preparations nonmitogenic for C3H/HeJ spleens, yet activity for other strains was only moderately decreased. These experiments would suggest either that the phenol treatment chemically alters the lipid A region of the LPS molecule or that such treatment removes the putative tightly bound contaminant responsible for C3H/HeJ mitogenesis. In the experiments reported here, we have explored in greater detail the role of lipid A in the stimulation of C3H/HeJ spleen cells. For these experiments we have utilized our earlier observations that the antibiotic polymyxin B forms a highly stable molecular complex with the lipid A region of LPS (4), and that such polymyxin B-LPS complexes are unable to mitogenically stimulate B lymphocytes (5). In addition, we have attempted to distinguish between the two potential modes of action of phenol on LPS, namely, the chemical alteration of the lipid A or the removal of a tightly bound contaminant by phenol treatment. The results of the experiments we report here support the interpretation that mitogenic activity of positive preparations of LPS is associated with a low mol wt phenol soluble polypeptide of approximately 10,000 mol wt. After partial purification, this polypeptide intitiates a significant mitogenic response at concentrations as low as 10 mug/ml. We conclude that the C3H/HeJ strain of mouse is a true nonresponder to the stimulatory effects of the lipid A region of LPS.", "contents": "Isolation of a lipid A bound polypeptide responsible for \"LPS-initiated\" mitogenesis of C3H/HeJ spleen cells. The experiments by Sultzer and Nilsson (1), and later by Watson and Riblet (2), established that spleen cells from the C3H/HeJ strain of mouse were refractory to the mitogenic effects of bacterial lipopolysaccharides (LPS). More recently, however, experiments from our laboratory (3) demonstrated that spleen cells from C3H/HeJ mice were in fact responsive to some preparations of LPS but not to others, and that the method of extraction played a critical role in determining activity. In particular, preparations of LPS prepared by extraction with aqueous butanol had potent mitogenic activity. Our data showed that the mitogenic activity of such positive preparations of LPS coisolated with the LPS during gel filtration chromatography and subsequent equilibrium banding on CsCl. In addition, lipid A isolated from positive preparations of LPS was also capable of stimulating C3H/HeJ spleen cells. Taken together, these experiments provided rather convincing data that it was the LPS (in particular the lipid A) itself, or some contaminant very tightly bound to the lipid A, which was responsible for its biological activity. We further demonstrated that treatment of positive preparations of LPS with hot phenol rendered such preparations nonmitogenic for C3H/HeJ spleens, yet activity for other strains was only moderately decreased. These experiments would suggest either that the phenol treatment chemically alters the lipid A region of the LPS molecule or that such treatment removes the putative tightly bound contaminant responsible for C3H/HeJ mitogenesis. In the experiments reported here, we have explored in greater detail the role of lipid A in the stimulation of C3H/HeJ spleen cells. For these experiments we have utilized our earlier observations that the antibiotic polymyxin B forms a highly stable molecular complex with the lipid A region of LPS (4), and that such polymyxin B-LPS complexes are unable to mitogenically stimulate B lymphocytes (5). In addition, we have attempted to distinguish between the two potential modes of action of phenol on LPS, namely, the chemical alteration of the lipid A or the removal of a tightly bound contaminant by phenol treatment. The results of the experiments we report here support the interpretation that mitogenic activity of positive preparations of LPS is associated with a low mol wt phenol soluble polypeptide of approximately 10,000 mol wt. After partial purification, this polypeptide intitiates a significant mitogenic response at concentrations as low as 10 mug/ml. We conclude that the C3H/HeJ strain of mouse is a true nonresponder to the stimulatory effects of the lipid A region of LPS."} {"id": "PMID:182901", "title": "Enzymatic determination of cholesterol in serum lipoproteins.", "content": "A new method for the quantitative determination of the cholesterol content of serum lipoprotein is described. Electrophoresis of the serum lipoproteins on agarose gel is followed by the enzymatic determination of the lipoprotein cholesterol. The cholesterol is released from the agarose pieces containing the lipoproteins by dissolving the agarose with HCl. No influence of the HCl on cholesterol, and no influence of the agarose degradation products on the enzyme reactions was observed. The analytical procedure is simple and only 20 mul serum are required. The average coefficient of variation for the determination of the beta-lipoprotein cholesterol less than 4%, and it is less than 8% in the pre-beta-lipoproteins of Type IV hyperlipidemic patients. The cholesterol contents found in the other lipoprotein fractions have to be interpreted as an approximation. Semiautomation seems to be possible. In preliminary studies, the cholesterol concentrations of the serum lipoproteins were determined in some control subjects and some hyperlipidemic patients. The results are in good agreement with data obtained by ultracentrifuge studies performed by other investigators. The advangates of this new procedure and aspects of application are discussed.", "contents": "Enzymatic determination of cholesterol in serum lipoproteins. A new method for the quantitative determination of the cholesterol content of serum lipoprotein is described. Electrophoresis of the serum lipoproteins on agarose gel is followed by the enzymatic determination of the lipoprotein cholesterol. The cholesterol is released from the agarose pieces containing the lipoproteins by dissolving the agarose with HCl. No influence of the HCl on cholesterol, and no influence of the agarose degradation products on the enzyme reactions was observed. The analytical procedure is simple and only 20 mul serum are required. The average coefficient of variation for the determination of the beta-lipoprotein cholesterol less than 4%, and it is less than 8% in the pre-beta-lipoproteins of Type IV hyperlipidemic patients. The cholesterol contents found in the other lipoprotein fractions have to be interpreted as an approximation. Semiautomation seems to be possible. In preliminary studies, the cholesterol concentrations of the serum lipoproteins were determined in some control subjects and some hyperlipidemic patients. The results are in good agreement with data obtained by ultracentrifuge studies performed by other investigators. The advangates of this new procedure and aspects of application are discussed."} {"id": "PMID:182902", "title": "A new enzymatic method for the determination of free and conjugated glucuronic acid.", "content": "A new method is reported for the quantitative determination of glucuronic and galacturonic acid, which is based on spectrophotometric measurement of NADH. The NAD-linked oxidation of the uronic acids to the corresponding dicarboxylic acids is measured in the presence of uronic acid dehydrogenase. This enzyme was isolated from Pseudomonas syringae. The test is highly specific for glucuronic and galacturonic acid and permits the exact determination of free and conjugated glucuronic acid. This enzymatic determination of glucuronic is the most sensitive method available today.", "contents": "A new enzymatic method for the determination of free and conjugated glucuronic acid. A new method is reported for the quantitative determination of glucuronic and galacturonic acid, which is based on spectrophotometric measurement of NADH. The NAD-linked oxidation of the uronic acids to the corresponding dicarboxylic acids is measured in the presence of uronic acid dehydrogenase. This enzyme was isolated from Pseudomonas syringae. The test is highly specific for glucuronic and galacturonic acid and permits the exact determination of free and conjugated glucuronic acid. This enzymatic determination of glucuronic is the most sensitive method available today."} {"id": "PMID:182904", "title": "Nonlocal interactions in the photoreceptor transduction process.", "content": "We have recently demonstated the dissection of the transduction process in the barnacle photoreceptor into antagonistic \"excitor\" and \"inhibitor\" processes. We now show that (a) the interaction between the two processes proceeds even when they are induced in different pigment molecules; (b) the excitor process appears to be slightly facilitated if those pigment molecular unaffected by the stimulus are in the stable metarhodopsin state or slightly inhibited if they are in the rhodopsin state; (c) there is a facilitatory interaction among the excitor processes induced in different pigment molecules. In case a, the interaction has a range of at least a few hundred angstroms, taking place in a time of less than a fraction of a second; in cases b and c, the range could be as little as \"nearest neighbors\" and the time as much as a few seconds. All these interactions could be intermediated by the \"excitor\" if it is a transmitter.", "contents": "Nonlocal interactions in the photoreceptor transduction process. We have recently demonstated the dissection of the transduction process in the barnacle photoreceptor into antagonistic \"excitor\" and \"inhibitor\" processes. We now show that (a) the interaction between the two processes proceeds even when they are induced in different pigment molecules; (b) the excitor process appears to be slightly facilitated if those pigment molecular unaffected by the stimulus are in the stable metarhodopsin state or slightly inhibited if they are in the rhodopsin state; (c) there is a facilitatory interaction among the excitor processes induced in different pigment molecules. In case a, the interaction has a range of at least a few hundred angstroms, taking place in a time of less than a fraction of a second; in cases b and c, the range could be as little as \"nearest neighbors\" and the time as much as a few seconds. All these interactions could be intermediated by the \"excitor\" if it is a transmitter."} {"id": "PMID:182905", "title": "Control of the sequential utilization of glucose and fructose by Escherichia coli.", "content": "In Escherichia coli (ATCCI5224; ML308), glucose and fructose phosphotransferase systems (PT-systems) are constitutive but activities are increased five and 10-fold respectively by aerobic growth on their respective substrates in defined media. In mixtures, glucose is used preferentially and the fructose PT-system activity is kept at its minimum; but, on glucose exhaustion, it overshoots its steady-state level and growth continues on fructose without lag. Cyclic AMP prevents overshoot. Continuous cultures operating as turbidostats on mixtures of glucose and fructose do not use fructose if sufficient glucose is present to support growth. If less glucose is available, it is all used and sufficient fructose is metabolized concurrently to maintain the growth rate characteristic of glucose. Both PT-systems are inhibited by hexose phosphates. Presence of homologous substrate specifically sensitizes each PT-system to inactivation by N-ethylmaleimide (NEM). Glucose diminishes the ability of fructose to sensitize its PT-system to NEM. This effect parallels the inhibition of fructose utilization by glucose and suggests that glucose denies fructose access to the fructose-specific part of the PT-system.", "contents": "Control of the sequential utilization of glucose and fructose by Escherichia coli. In Escherichia coli (ATCCI5224; ML308), glucose and fructose phosphotransferase systems (PT-systems) are constitutive but activities are increased five and 10-fold respectively by aerobic growth on their respective substrates in defined media. In mixtures, glucose is used preferentially and the fructose PT-system activity is kept at its minimum; but, on glucose exhaustion, it overshoots its steady-state level and growth continues on fructose without lag. Cyclic AMP prevents overshoot. Continuous cultures operating as turbidostats on mixtures of glucose and fructose do not use fructose if sufficient glucose is present to support growth. If less glucose is available, it is all used and sufficient fructose is metabolized concurrently to maintain the growth rate characteristic of glucose. Both PT-systems are inhibited by hexose phosphates. Presence of homologous substrate specifically sensitizes each PT-system to inactivation by N-ethylmaleimide (NEM). Glucose diminishes the ability of fructose to sensitize its PT-system to NEM. This effect parallels the inhibition of fructose utilization by glucose and suggests that glucose denies fructose access to the fructose-specific part of the PT-system."} {"id": "PMID:182906", "title": "Metabolism of L-rhamnose in Arthrobacter pyridinolis.", "content": "In Arthrobacter pyridinolis, a respiration-coupled transport system for L-rhamnose caused accumulation of free L-rhamnose, while a phosphoenolpyruvate: L-rhamnose phosphotransferase system caused accumulation of L-rhamnose I-phosphate (Levinson & Krulwich, 1974). The pathways for subsequent metabolism of L-rhamnose and L-rhamose I-phosphate have now been investigated. Arthrobacter pyridinolis contains an inducible L-rhamnose isomerase and L-rhamnulokinase, as well as a constitutive L-rhamnulose I-phosphate aldolase. Results with mutants which are unable to metabolize L-rhamnose suggest the presence of an L-rhamnose I-phosphate phosphatase, which forms free L-rhamnose by hydrolysis of L-rhamnose I-phosphate produced by the phosphotransferase system. Mutants which lack this enzyme exhibited severe inhibition of growth in the presence of L-rhamnose plus any of a variety of carbon sources. There is some evidence that this inhibition was due to accumulation of L-rhamnose I-phosphate at toxic concentrations within the bacteria. The metabolism of L-rhamnose transported by the phosphotransferase system therefore appears to occur by hydrolysis of L-rhamnose I-phosphate to free L-rhamnose by a phosphatase. Metabolism of the L-rhamnose thus produced, and of that accumulated by the respiration-coupled transport system, the proceeds by the sequence of reactions: L-rhamnose leads to L-rhamnulose leads to L=rhamnulose I-phosphate leads to dihydroxyacetone phosphate plus L-lactaldehyde.", "contents": "Metabolism of L-rhamnose in Arthrobacter pyridinolis. In Arthrobacter pyridinolis, a respiration-coupled transport system for L-rhamnose caused accumulation of free L-rhamnose, while a phosphoenolpyruvate: L-rhamnose phosphotransferase system caused accumulation of L-rhamnose I-phosphate (Levinson & Krulwich, 1974). The pathways for subsequent metabolism of L-rhamnose and L-rhamose I-phosphate have now been investigated. Arthrobacter pyridinolis contains an inducible L-rhamnose isomerase and L-rhamnulokinase, as well as a constitutive L-rhamnulose I-phosphate aldolase. Results with mutants which are unable to metabolize L-rhamnose suggest the presence of an L-rhamnose I-phosphate phosphatase, which forms free L-rhamnose by hydrolysis of L-rhamnose I-phosphate produced by the phosphotransferase system. Mutants which lack this enzyme exhibited severe inhibition of growth in the presence of L-rhamnose plus any of a variety of carbon sources. There is some evidence that this inhibition was due to accumulation of L-rhamnose I-phosphate at toxic concentrations within the bacteria. The metabolism of L-rhamnose transported by the phosphotransferase system therefore appears to occur by hydrolysis of L-rhamnose I-phosphate to free L-rhamnose by a phosphatase. Metabolism of the L-rhamnose thus produced, and of that accumulated by the respiration-coupled transport system, the proceeds by the sequence of reactions: L-rhamnose leads to L-rhamnulose leads to L=rhamnulose I-phosphate leads to dihydroxyacetone phosphate plus L-lactaldehyde."} {"id": "PMID:182907", "title": "The uptake and metabolism of glucose, maltose and starch by the rumen ciliate Epidinium ecaudatum caudatum.", "content": "[14C]Glucose taken up by Epidinium ecaudatum caudatum was found in the pool, in the protozoal polysaccharide and in the bacteria associated with the protozoa. The amount incorporated into the polysaccharide depended on the square of the glucose concentration. Evidence was obtained that glucose was probably taken up initially into the pool unchanged, and then rapidly converted into glucose 6-phosphate and maltose which were subsequently hydrolysed to glucose. [14C]-Maltose was taken up at 20 to 30% of the rate of [14C]glucose, with 14C appearing initially in maltose and glucose 6-phosphate. 14C from 14C-labelled soluble starch appeared in the pool as maltose, glucose 6-phosphate and glucose in that order, but incorporation into protozoal polysaccaride was poor. Hexokinase, phosphoglucomutase, alpha-glucan and maltose phosphorylases, glucose 6-phosphatase and maltase activities were found in the protozoa.", "contents": "The uptake and metabolism of glucose, maltose and starch by the rumen ciliate Epidinium ecaudatum caudatum. [14C]Glucose taken up by Epidinium ecaudatum caudatum was found in the pool, in the protozoal polysaccharide and in the bacteria associated with the protozoa. The amount incorporated into the polysaccharide depended on the square of the glucose concentration. Evidence was obtained that glucose was probably taken up initially into the pool unchanged, and then rapidly converted into glucose 6-phosphate and maltose which were subsequently hydrolysed to glucose. [14C]-Maltose was taken up at 20 to 30% of the rate of [14C]glucose, with 14C appearing initially in maltose and glucose 6-phosphate. 14C from 14C-labelled soluble starch appeared in the pool as maltose, glucose 6-phosphate and glucose in that order, but incorporation into protozoal polysaccaride was poor. Hexokinase, phosphoglucomutase, alpha-glucan and maltose phosphorylases, glucose 6-phosphatase and maltase activities were found in the protozoa."} {"id": "PMID:182908", "title": "Herpes virus and viral DNA synthesis in ultraviolet light-irradiated cells.", "content": "The rate of virus DNA synthesis and the production of infectious virus are impaired in stationary monkey kidney CV-I cells irradiated with u.v. before infection with herpes simplex virus (HSV). The inhibition of HSV multiplication is due to u.v.-induced damage in cell DNA. CV-I cells recover their capacity to support HSV growth during the 40 to 48 h after irradiation, and the final virus yield is enhanced by a factor of 10. The time course of the recovery is similar to that of the excision repair process occurring in u.v.-irradiated mammalian cells. Caffeine, hydroxyurea and cycloheximide inhibit the recovery. Fluorodeoxyuridine is without effect. A small but significant amount of labelled dThd coming from irradiated cell DNA is incorporated into virus DNA. HSV specified thymidine kinase seems to be more effective for virus DNA synthesis in irradiated than in control cells.", "contents": "Herpes virus and viral DNA synthesis in ultraviolet light-irradiated cells. The rate of virus DNA synthesis and the production of infectious virus are impaired in stationary monkey kidney CV-I cells irradiated with u.v. before infection with herpes simplex virus (HSV). The inhibition of HSV multiplication is due to u.v.-induced damage in cell DNA. CV-I cells recover their capacity to support HSV growth during the 40 to 48 h after irradiation, and the final virus yield is enhanced by a factor of 10. The time course of the recovery is similar to that of the excision repair process occurring in u.v.-irradiated mammalian cells. Caffeine, hydroxyurea and cycloheximide inhibit the recovery. Fluorodeoxyuridine is without effect. A small but significant amount of labelled dThd coming from irradiated cell DNA is incorporated into virus DNA. HSV specified thymidine kinase seems to be more effective for virus DNA synthesis in irradiated than in control cells."} {"id": "PMID:182909", "title": "Chicken egg yolk enhances focus formation by subgroup B, C and D rous sarcoma viruses.", "content": "Focus formation by Rous sarcoma virus (RSV) was significantly enhanced when virus was incubated with the saline fraction of chloroform extracted chicken egg yolk, prior to infecting chicken embryo cells. The enhancement was restricted to members of RSV subgroups B, C and D and was proportional to yolk dilution. Subgroup A virus was never affected. In all, 108 yolk samples from specific pathogen free chickens were investigated. Of these 78 to 97% stimulated focus formation. RSV(RAV-50) of subgroup D which was stimulated up to tenfold, was the most strongly affected strain. The enhancing principle was shown to be a specific yolk factor, and its effect remained constant even after several years' storage. Crude yolk specimens showed essentially the same enhancing property. The chemical nature of the yolk factor is still unknown. It must, however, be taken into account when assaying for avian leukosis virus antibodies.", "contents": "Chicken egg yolk enhances focus formation by subgroup B, C and D rous sarcoma viruses. Focus formation by Rous sarcoma virus (RSV) was significantly enhanced when virus was incubated with the saline fraction of chloroform extracted chicken egg yolk, prior to infecting chicken embryo cells. The enhancement was restricted to members of RSV subgroups B, C and D and was proportional to yolk dilution. Subgroup A virus was never affected. In all, 108 yolk samples from specific pathogen free chickens were investigated. Of these 78 to 97% stimulated focus formation. RSV(RAV-50) of subgroup D which was stimulated up to tenfold, was the most strongly affected strain. The enhancing principle was shown to be a specific yolk factor, and its effect remained constant even after several years' storage. Crude yolk specimens showed essentially the same enhancing property. The chemical nature of the yolk factor is still unknown. It must, however, be taken into account when assaying for avian leukosis virus antibodies."} {"id": "PMID:182910", "title": "Evidence that detergent-reactivated interferons are not renatured.", "content": "The sedimentation rate of human leukocyte interferon (HLIF) reactivated from sodium dodecyl sulphate (SDS) solution was studied by glycerol gradient centrifugation and compared to that of native HLIF. Reactivated HLIF consistently sedimented faster than native HLIF, indicating that full recovery of antiviral activity does not require renaturation of the entire interferon molecule.", "contents": "Evidence that detergent-reactivated interferons are not renatured. The sedimentation rate of human leukocyte interferon (HLIF) reactivated from sodium dodecyl sulphate (SDS) solution was studied by glycerol gradient centrifugation and compared to that of native HLIF. Reactivated HLIF consistently sedimented faster than native HLIF, indicating that full recovery of antiviral activity does not require renaturation of the entire interferon molecule."} {"id": "PMID:182911", "title": "Multiplication of vesicular stomatitis virus in the leafhopper Peregrinus maidis (Ashm.), a vector of a plant rhabdovirus.", "content": "Vesicular stomatitis virus (VSV) was found to multiply efficiently in whole Peregrinus maidis (Ashm.). the leafhopper vector of maize mosaic virus (MMV), a plant rhabdovirus. Insects were inoculated with VSV by means of a microsyringe, collected at 1-day intervals and tested individually for the presence of virus. Exponential virus multiplication occurred within the first 4 days, reaching titres of 10(6) p.f.u. per insect in days 5 to 10 after inoculation. These observations show that a common host is avialable to study the multiplication of a plant and an animal rhabdovirus.", "contents": "Multiplication of vesicular stomatitis virus in the leafhopper Peregrinus maidis (Ashm.), a vector of a plant rhabdovirus. Vesicular stomatitis virus (VSV) was found to multiply efficiently in whole Peregrinus maidis (Ashm.). the leafhopper vector of maize mosaic virus (MMV), a plant rhabdovirus. Insects were inoculated with VSV by means of a microsyringe, collected at 1-day intervals and tested individually for the presence of virus. Exponential virus multiplication occurred within the first 4 days, reaching titres of 10(6) p.f.u. per insect in days 5 to 10 after inoculation. These observations show that a common host is avialable to study the multiplication of a plant and an animal rhabdovirus."} {"id": "PMID:182912", "title": "Subregional localization of the gene(s) governing the human interferon induced antiviral state in man.", "content": "A dosage effect of chromosomal translocation was used to locate the gene(s) which codes for the human interferon induced antiviral state on the long arm of chromosome 21.", "contents": "Subregional localization of the gene(s) governing the human interferon induced antiviral state in man. A dosage effect of chromosomal translocation was used to locate the gene(s) which codes for the human interferon induced antiviral state on the long arm of chromosome 21."} {"id": "PMID:182913", "title": "Investigation of the anti-viral mechanism of poly I and poly C against encephalomyocarditis virus infection in the absence of interferon induction in mice.", "content": "Protection of mice against EMC virus infection by poly C and poly I has already been distinguished from interferon mediated protection in several ways. Transfer of serum from EMC virus infected and poly C or poly I treated mice to donor mice that were then infected shows that the anti-viral effect of the single-stranded polynucleotides is not due to boosting interferon produced by infection itself in the way that inferferon can be 'primed' in vitro. Mice surviving infections of more than I X LD100 as a result of poly C or poly I treatment show no protection against re-infection 15 days after the first infection, indicating no long-term stimulation of immune responses to the virus. Mice treated with an immunosuppressive regime of cytosine arabinoside can be protected against EMC virus infection with poly C and poly I treatment and athymic 'nude' mice can also be protected. The possibility of IgM stimulation by poly C and poly I seems unlikely from experiments in which serum was transferred from mice treated with the polynucleotides and an inactivated EMC 'vaccine' to recipient mice which were then challenged with infectious virus. Protection of mice against EMC virus by the single-stranded polynucleotides is abolished by administration of silica to the mice, implying an involvement of macrophages in the protective effects of poly C and poly I. The possibility that the polynucleotides stimulate clearance of virus particles, at least from immunologically responsive regions of the mouse, has been discounted by the inability of polynucleotide treatment to suppress 'vaccine' mediated protection of mice. These results indicate that macrophages are involved in the anti-viral effects of poly C and poly I either because they inhibit replication of the virus in macrophages or because direct anti-viral properties of macrophages are activated by the polynucleotides.", "contents": "Investigation of the anti-viral mechanism of poly I and poly C against encephalomyocarditis virus infection in the absence of interferon induction in mice. Protection of mice against EMC virus infection by poly C and poly I has already been distinguished from interferon mediated protection in several ways. Transfer of serum from EMC virus infected and poly C or poly I treated mice to donor mice that were then infected shows that the anti-viral effect of the single-stranded polynucleotides is not due to boosting interferon produced by infection itself in the way that inferferon can be 'primed' in vitro. Mice surviving infections of more than I X LD100 as a result of poly C or poly I treatment show no protection against re-infection 15 days after the first infection, indicating no long-term stimulation of immune responses to the virus. Mice treated with an immunosuppressive regime of cytosine arabinoside can be protected against EMC virus infection with poly C and poly I treatment and athymic 'nude' mice can also be protected. The possibility of IgM stimulation by poly C and poly I seems unlikely from experiments in which serum was transferred from mice treated with the polynucleotides and an inactivated EMC 'vaccine' to recipient mice which were then challenged with infectious virus. Protection of mice against EMC virus by the single-stranded polynucleotides is abolished by administration of silica to the mice, implying an involvement of macrophages in the protective effects of poly C and poly I. The possibility that the polynucleotides stimulate clearance of virus particles, at least from immunologically responsive regions of the mouse, has been discounted by the inability of polynucleotide treatment to suppress 'vaccine' mediated protection of mice. These results indicate that macrophages are involved in the anti-viral effects of poly C and poly I either because they inhibit replication of the virus in macrophages or because direct anti-viral properties of macrophages are activated by the polynucleotides."} {"id": "PMID:182914", "title": "Persistent herpes simplex virus infections established in two Burkitt lymphoma derived cell lines.", "content": "Examination of P3HR-I cells (Epstein-Barr virus [EBV] producer) persistently infected with the MAL strain of herpes simplex virus type I (HSV-I) suggested that only a few cells were actively producing a virus indistinguishable from HSV-I (MAL) despite the presence of immunofluorescent HSV-I antigens associated with the majority of cells. EBV-specific immunofluorescence was not altered in HSV-I persistently infected P3HR-I cells. HSV-I persistently infected cells, labelled for 72 h with 14C-thymidine, incorporated approx. 8% of the label into cell associated HSV-I DNA as resolved by caesium chloride gradients. Values greater than 8% of the total were suggested by hybridization of gradient fractions with 3H-HSV-I DNA. To determine whether the establishment of HSV persistent infections in Burkitt lymphoma derived cells was a general phenomenon, six strains of HSV-I (MAL, KOS, Patton, Syn R, BF and SYN V) and two strains of type 2 (333 and MS) were used to infect the P3HR-I and Raji (EBV non-producer) cell lines derived from Burkitt lymphomas. In P3HR-I cells, persistent infections were established with all strains of HSV-I but not with HSV-2. In Raji cells, persistent infections were established with all strains of HSV-I, except Syn V, and with both strains of HSV-2. No external support was required to maintain these infections.", "contents": "Persistent herpes simplex virus infections established in two Burkitt lymphoma derived cell lines. Examination of P3HR-I cells (Epstein-Barr virus [EBV] producer) persistently infected with the MAL strain of herpes simplex virus type I (HSV-I) suggested that only a few cells were actively producing a virus indistinguishable from HSV-I (MAL) despite the presence of immunofluorescent HSV-I antigens associated with the majority of cells. EBV-specific immunofluorescence was not altered in HSV-I persistently infected P3HR-I cells. HSV-I persistently infected cells, labelled for 72 h with 14C-thymidine, incorporated approx. 8% of the label into cell associated HSV-I DNA as resolved by caesium chloride gradients. Values greater than 8% of the total were suggested by hybridization of gradient fractions with 3H-HSV-I DNA. To determine whether the establishment of HSV persistent infections in Burkitt lymphoma derived cells was a general phenomenon, six strains of HSV-I (MAL, KOS, Patton, Syn R, BF and SYN V) and two strains of type 2 (333 and MS) were used to infect the P3HR-I and Raji (EBV non-producer) cell lines derived from Burkitt lymphomas. In P3HR-I cells, persistent infections were established with all strains of HSV-I but not with HSV-2. In Raji cells, persistent infections were established with all strains of HSV-I, except Syn V, and with both strains of HSV-2. No external support was required to maintain these infections."} {"id": "PMID:182915", "title": "Relationship between establishment of persistent infection of haemagglutinating virus of Japan and the properties of the virus.", "content": "The infectious virus (HVJ-pi) obtained from BHK cells persistently infected with haemagglutinating virus of Japan was found to be temperature-sensitive as well as causing little or no cytopathic effect (c.p.e.) and leading to establishment of carrier cultures in several cell lines at both permissive (32 degrees C) and non-permissive (38 degrees C) temperature. In order to obtain information about the role of HVJ-pi in the establishment of persistent infection, comparative studies were made of some phenotypic properties of HVJ-pi and HVJ-38 which was obtained by passing wild-type HVJ in eggs at 38 degrees C and was proved to be highly cytopathic. HVJ-pi differed from HVJ-38 in (1) temperature sensitivity in its ability to produce virus progeny, (2) infectivity for embryonated eggs, (3) neuraminidase activity, (4) the thermal stability of HA and neuraminidase activity, and (5) the polypeptide composition of BHK-grown viruses. B cells infected with HVJ-pi release haemagglutinin more efficiently, and less HA was accumulated on the cell membrane. In considering these results, it was concluded that the difference of envelope proteins might be involved in the striking difference in c.p.e. between HJV-pi and HVJ-38.", "contents": "Relationship between establishment of persistent infection of haemagglutinating virus of Japan and the properties of the virus. The infectious virus (HVJ-pi) obtained from BHK cells persistently infected with haemagglutinating virus of Japan was found to be temperature-sensitive as well as causing little or no cytopathic effect (c.p.e.) and leading to establishment of carrier cultures in several cell lines at both permissive (32 degrees C) and non-permissive (38 degrees C) temperature. In order to obtain information about the role of HVJ-pi in the establishment of persistent infection, comparative studies were made of some phenotypic properties of HVJ-pi and HVJ-38 which was obtained by passing wild-type HVJ in eggs at 38 degrees C and was proved to be highly cytopathic. HVJ-pi differed from HVJ-38 in (1) temperature sensitivity in its ability to produce virus progeny, (2) infectivity for embryonated eggs, (3) neuraminidase activity, (4) the thermal stability of HA and neuraminidase activity, and (5) the polypeptide composition of BHK-grown viruses. B cells infected with HVJ-pi release haemagglutinin more efficiently, and less HA was accumulated on the cell membrane. In considering these results, it was concluded that the difference of envelope proteins might be involved in the striking difference in c.p.e. between HJV-pi and HVJ-38."} {"id": "PMID:182916", "title": "Polykaryocyte formation induced by VSV in mouse L cells.", "content": "Infection of mouse L cells with VSV leads to the formation of polykaryocytes about 4 to 12 h p.i. When anti-VSV immune serum was added during the course of infection, progression of cell fusion was soon suppressed. Cycloheximide completely suppressed the cell fusion when the drug was added within 1 h p.i., while the cell fusion was not suppressed at all when the drug was added at and after 3 h. Early polykaryocyte formation, 'fusion from without', was observed only at a low level in cells infected at very high multiplicities. The development of cell fusion induced by VSV was found to be different in several cell types, although all these cells produced a rather high yield of virus: L and C-243-3 mouse cell lines showed a high level of polykaryocytosis (80 to 100%), BHK and RK-13 cells responded at low level, and PS and Vero cells showed no cell fusion in response to VSV infection. In PS cells, however, cell fusion occurred when VSV-infected L cells were co-cultivated. From these observations, the mechanism of cell fusion induced by VSV was discussed.", "contents": "Polykaryocyte formation induced by VSV in mouse L cells. Infection of mouse L cells with VSV leads to the formation of polykaryocytes about 4 to 12 h p.i. When anti-VSV immune serum was added during the course of infection, progression of cell fusion was soon suppressed. Cycloheximide completely suppressed the cell fusion when the drug was added within 1 h p.i., while the cell fusion was not suppressed at all when the drug was added at and after 3 h. Early polykaryocyte formation, 'fusion from without', was observed only at a low level in cells infected at very high multiplicities. The development of cell fusion induced by VSV was found to be different in several cell types, although all these cells produced a rather high yield of virus: L and C-243-3 mouse cell lines showed a high level of polykaryocytosis (80 to 100%), BHK and RK-13 cells responded at low level, and PS and Vero cells showed no cell fusion in response to VSV infection. In PS cells, however, cell fusion occurred when VSV-infected L cells were co-cultivated. From these observations, the mechanism of cell fusion induced by VSV was discussed."} {"id": "PMID:182917", "title": "2-Deoxy-D-glucose uptake by chick embryo cells: a biochemical indicator of genetic susceptibility to RNA tumour viruses.", "content": "The enhanced glucose uptake by chick embryo cells as early as 72 h after infection with Rous sarcoma virus (RSV) was confirmed in this study to be an early indicator of cellular transformation. The glucose uptake of C/E BrL cells infected by various doses of BS-RSV of subgroup A showed that the relationship between the log-dose of virus and log-uptake was linear (slope, b1 = 1.30 +/- 0.14) when the ratio of the number of infectious virus particles to the number of cells in the culture was above 1:200. But infection of cultures with a relatively high dose of virus, for instance 10(3.5) focus forming units (f.f.u.) was ineffective for the measurement of cellular transformation using the criterion of glucose uptake, whereas a much lower dose such as 10(1.7) f.f.u. was sufficient to induce foci of transformed cells. We concluded therefore that the statistic of glucose uptake assay (GUA) measured at 72 p.i. is less sensitive than that of the focus count assay (FCA) measured after 10 days as a measure of assessing cellular transformation by RSV. Nevertheless, when the cultures were infected with a higher dose of virus (10(4.3) f.f.u. or more), the GUA could discriminate between the transformed (T) and non-transformed (NT) cultures. This was demonstrated in the two genetic crosses, line 7-2 X WC(F1) and line 7-2 C line. Embryo cultures of these two test-crosses were infected with viruses of subgroups A, B, C and D, and the T and NT phenotypes were ascertained. Also, on the basis of focus counts in the cultures the genetically resistant (R) and susceptible (S) phenotypes in response to various infections were determined. The T and NT phenotypes based on the GUA were compared with the S and R phenotypes, respectively, based on the FCA. It was found that in 47 of the 51 cultures, the phenotypic agreement was perfect, suggesting that glucose uptake by cells of embryo cultures exposed to RSV is a biochemical indicator of genetic susceptibility. The discordant results in 4 cultures are discussed in the light of present knowledge of cellular transformation by RSV.", "contents": "2-Deoxy-D-glucose uptake by chick embryo cells: a biochemical indicator of genetic susceptibility to RNA tumour viruses. The enhanced glucose uptake by chick embryo cells as early as 72 h after infection with Rous sarcoma virus (RSV) was confirmed in this study to be an early indicator of cellular transformation. The glucose uptake of C/E BrL cells infected by various doses of BS-RSV of subgroup A showed that the relationship between the log-dose of virus and log-uptake was linear (slope, b1 = 1.30 +/- 0.14) when the ratio of the number of infectious virus particles to the number of cells in the culture was above 1:200. But infection of cultures with a relatively high dose of virus, for instance 10(3.5) focus forming units (f.f.u.) was ineffective for the measurement of cellular transformation using the criterion of glucose uptake, whereas a much lower dose such as 10(1.7) f.f.u. was sufficient to induce foci of transformed cells. We concluded therefore that the statistic of glucose uptake assay (GUA) measured at 72 p.i. is less sensitive than that of the focus count assay (FCA) measured after 10 days as a measure of assessing cellular transformation by RSV. Nevertheless, when the cultures were infected with a higher dose of virus (10(4.3) f.f.u. or more), the GUA could discriminate between the transformed (T) and non-transformed (NT) cultures. This was demonstrated in the two genetic crosses, line 7-2 X WC(F1) and line 7-2 C line. Embryo cultures of these two test-crosses were infected with viruses of subgroups A, B, C and D, and the T and NT phenotypes were ascertained. Also, on the basis of focus counts in the cultures the genetically resistant (R) and susceptible (S) phenotypes in response to various infections were determined. The T and NT phenotypes based on the GUA were compared with the S and R phenotypes, respectively, based on the FCA. It was found that in 47 of the 51 cultures, the phenotypic agreement was perfect, suggesting that glucose uptake by cells of embryo cultures exposed to RSV is a biochemical indicator of genetic susceptibility. The discordant results in 4 cultures are discussed in the light of present knowledge of cellular transformation by RSV."} {"id": "PMID:182918", "title": "Fugue states in sleep and wakefulness: a psychophysiological study.", "content": "A patient's refusal to participate in recommended treatment is a problem faced in all branches of medicine. However, psychiatry faces special problems because of its authority to impose hospitalization and treatment on unwilling patients. Nowhere is this more poignant than in the treatment of patients exhibiting suicidal behavior where the potential for imminent self-destruction exists. As part of a prospective study to develop utilization review standards for the hospitalization of suicide attempters, cases were identified where there was independent agreement between both the experts' standards and the treating resident psychiatrists that hospitalization was required. Despite this agreement, the patients were not hospitalized because the patients refused. By most criteria, these patients were a high risk group. They had made repeated suicide attempts, used lethal means which eventuated in serious medical consequences, and were still suicidal when referred for treatment. The emergency room psychiatrists reported feeling confused, anxious, and annoyed in dealing with these patients, and the patients signed out against medical advice. A review of these cases indicates that discussions of social control vs. medical responsibility and clear criteria for hospitalization should be incorporated into residency training programs since the emergency room resident faces these tension-producing issues frequently with several different types of patients. Moreover, utilization review criteria may help to set standards which will assist the psychiatrist in making these difficult decisions.", "contents": "Fugue states in sleep and wakefulness: a psychophysiological study. A patient's refusal to participate in recommended treatment is a problem faced in all branches of medicine. However, psychiatry faces special problems because of its authority to impose hospitalization and treatment on unwilling patients. Nowhere is this more poignant than in the treatment of patients exhibiting suicidal behavior where the potential for imminent self-destruction exists. As part of a prospective study to develop utilization review standards for the hospitalization of suicide attempters, cases were identified where there was independent agreement between both the experts' standards and the treating resident psychiatrists that hospitalization was required. Despite this agreement, the patients were not hospitalized because the patients refused. By most criteria, these patients were a high risk group. They had made repeated suicide attempts, used lethal means which eventuated in serious medical consequences, and were still suicidal when referred for treatment. The emergency room psychiatrists reported feeling confused, anxious, and annoyed in dealing with these patients, and the patients signed out against medical advice. A review of these cases indicates that discussions of social control vs. medical responsibility and clear criteria for hospitalization should be incorporated into residency training programs since the emergency room resident faces these tension-producing issues frequently with several different types of patients. Moreover, utilization review criteria may help to set standards which will assist the psychiatrist in making these difficult decisions."} {"id": "PMID:182919", "title": "Urinary cyclic AMP in relation to lithium treatment in manic-depressive illness.", "content": "Urnary cyclic AMP was measured longitudinally in six patients with bipolar affective disorder. The values varied from 3.55 to 19.0 mugmol/24 hours with considerable variation between subjects. Three of these patients improved with administration of lithium carbonate. This improvement was not correlated with a change in cyclic AMP excretion. Five normal male volunteers were studied over a 5-day period. The urinary excretion for this group showed the same large intersubject variability but smaller intrasubject variation as was found for the patient group. It is suggested that erroneous results may be obtained for urinary cyclic AMP excretion if mean group values are used from patients not studied longitudinally.", "contents": "Urinary cyclic AMP in relation to lithium treatment in manic-depressive illness. Urnary cyclic AMP was measured longitudinally in six patients with bipolar affective disorder. The values varied from 3.55 to 19.0 mugmol/24 hours with considerable variation between subjects. Three of these patients improved with administration of lithium carbonate. This improvement was not correlated with a change in cyclic AMP excretion. Five normal male volunteers were studied over a 5-day period. The urinary excretion for this group showed the same large intersubject variability but smaller intrasubject variation as was found for the patient group. It is suggested that erroneous results may be obtained for urinary cyclic AMP excretion if mean group values are used from patients not studied longitudinally."} {"id": "PMID:182920", "title": "Magnesium-resistant excitatory synaptic potentials in the leech Retzius cell.", "content": "Postsynaptic potentials (PSPs) recorded from leech Retzius cells in response to stimulation of interganglionic connective could not be reversed by soma depolarization or abolished by 40 mM Mg ion, nor could input resistance changes be detected during them. Alteration of external Cl and K over a tenfold range provided no clear evidence that the PSPs involved a conductance change to either ion. The method of extrapolation yielded an apparent PSP equilibrium potential of about -20 mV. The steep portion of the relationship between Retzius cell action potential amplitude and membrane potential extrapolated to an apparent reversal potential of -13 mV. It is likely that the connective-to-Retzius cell PSPs were principally electrical events. Their apparent reversal potentials could have been in the range associated with chemical synapses because they traversed an electrical synapse with a variable coupling resistance, or because the polarizing currents, passing \"backwards\" across electrical synapses, changed the amplitude of the presynaptic action potentials.", "contents": "Magnesium-resistant excitatory synaptic potentials in the leech Retzius cell. Postsynaptic potentials (PSPs) recorded from leech Retzius cells in response to stimulation of interganglionic connective could not be reversed by soma depolarization or abolished by 40 mM Mg ion, nor could input resistance changes be detected during them. Alteration of external Cl and K over a tenfold range provided no clear evidence that the PSPs involved a conductance change to either ion. The method of extrapolation yielded an apparent PSP equilibrium potential of about -20 mV. The steep portion of the relationship between Retzius cell action potential amplitude and membrane potential extrapolated to an apparent reversal potential of -13 mV. It is likely that the connective-to-Retzius cell PSPs were principally electrical events. Their apparent reversal potentials could have been in the range associated with chemical synapses because they traversed an electrical synapse with a variable coupling resistance, or because the polarizing currents, passing \"backwards\" across electrical synapses, changed the amplitude of the presynaptic action potentials."} {"id": "PMID:182926", "title": "Peripheral nerve abnormalities related to galactose administration in rats.", "content": "Electrophysiological, biochemical, and morphometric observations were made on the peripheral nerves of rats after galactose feeding. Motor nerve conduction velocity was found to be reduced. This was associated with an accumulation of galactitol in the peripheral nerves and a diminution in their myoinositol content. An increased water content and fascicular area, taken in conjunction with a probable increase in the area of the endoneurial spaces, indicated overhydration of the peripheral nerves. Morphometric observations on the myelinated fibre population in the tibial nerve showed no loss of fibres and although both the maximal and the average diameter of the myelinated fibres was slightly less than in age-matched controls, this was insufficient to explain the reduction in conduction velocity. Segmental demyelination was not detected and the relationship between myelin thickness and axon circumference was not altered. Electron microscope observations revealed no ultrastructural changes in the myelinated fibres and, in particular, no abnormalities at the nodes of Ranvier or indication of abnormal hydration of the Schwann cells. The relevance of these findings to the peripheral nerve changes in human and experimental diabetes is discussed.", "contents": "Peripheral nerve abnormalities related to galactose administration in rats. Electrophysiological, biochemical, and morphometric observations were made on the peripheral nerves of rats after galactose feeding. Motor nerve conduction velocity was found to be reduced. This was associated with an accumulation of galactitol in the peripheral nerves and a diminution in their myoinositol content. An increased water content and fascicular area, taken in conjunction with a probable increase in the area of the endoneurial spaces, indicated overhydration of the peripheral nerves. Morphometric observations on the myelinated fibre population in the tibial nerve showed no loss of fibres and although both the maximal and the average diameter of the myelinated fibres was slightly less than in age-matched controls, this was insufficient to explain the reduction in conduction velocity. Segmental demyelination was not detected and the relationship between myelin thickness and axon circumference was not altered. Electron microscope observations revealed no ultrastructural changes in the myelinated fibres and, in particular, no abnormalities at the nodes of Ranvier or indication of abnormal hydration of the Schwann cells. The relevance of these findings to the peripheral nerve changes in human and experimental diabetes is discussed."} {"id": "PMID:182927", "title": "Progressive multifocal neurologic deficit with disseminated subpial demyelination.", "content": "A sixty-six year-old man developed visual and gait difficulties, a deficit in recent memory and hearing, and acute urinary retention. He subsequently became blind, deaf, and quadriparetic. Terminally, weakness deepended and he lapsed into semi-coma. The cerebrospinal fluid contained increased amounts of protein with a normal electrophoretic pattern, and a moderate mononuclear pleocytosis. Gross examination of the brain revealed normal vessels and meninges. Coronal sections showed irregular areas of subpial discoloration in forebrain and brainstem. Stains for myelin revealed scattered foci of pallor in the intracortical myelinated fibers; demyelination throughout the brainstem, most severe in subpial areas; and a focus of central pontine myelin loss. The subependymal myelin was intact throughout the neuraxis. Histological examination showed axonal preservation in areas of extreme myelin loss. Demyelination was accompanied by astrocytic gliosis showing different degrees of activity, and occasional perivascular cuffing with mononuclear cells in cerebral and meningeal vessels. Electron microscopy revealed filamentous structures in cell nuclei. These were 180-220 A in diameter, had a hollow core, and, in some tangential sections, showed cross striations. The unusual clinical picture and correspondingly striking pattern of demyelination suggest that this case might represent a distinct clinical entity.", "contents": "Progressive multifocal neurologic deficit with disseminated subpial demyelination. A sixty-six year-old man developed visual and gait difficulties, a deficit in recent memory and hearing, and acute urinary retention. He subsequently became blind, deaf, and quadriparetic. Terminally, weakness deepended and he lapsed into semi-coma. The cerebrospinal fluid contained increased amounts of protein with a normal electrophoretic pattern, and a moderate mononuclear pleocytosis. Gross examination of the brain revealed normal vessels and meninges. Coronal sections showed irregular areas of subpial discoloration in forebrain and brainstem. Stains for myelin revealed scattered foci of pallor in the intracortical myelinated fibers; demyelination throughout the brainstem, most severe in subpial areas; and a focus of central pontine myelin loss. The subependymal myelin was intact throughout the neuraxis. Histological examination showed axonal preservation in areas of extreme myelin loss. Demyelination was accompanied by astrocytic gliosis showing different degrees of activity, and occasional perivascular cuffing with mononuclear cells in cerebral and meningeal vessels. Electron microscopy revealed filamentous structures in cell nuclei. These were 180-220 A in diameter, had a hollow core, and, in some tangential sections, showed cross striations. The unusual clinical picture and correspondingly striking pattern of demyelination suggest that this case might represent a distinct clinical entity."} {"id": "PMID:182930", "title": "Acute myocardial infarction imaged with 99mTc-stannous pyrophosphate and 201Tl: a clinical evaluation.", "content": "Twenty-six patients suspected of having acute myocardial infarction (AMI) underwent myocardial scintigraphy sequentially with 201Tl and 99mTc-stannous pyrophosphate (99mTc-PPi). Of the 26 patients, 24 had AMI documented by enzyme and electrocardiographic changes. Nineteen had transmural and five had subendocardial myocardial infarctions. The remaining two patients had \"unstable angina pectoris.\" The mean time from onset to imaging was 4 days. Of the 24 patients with AMI, 22 had positive 99mTc-PPi scintigrams. In 20 the area of acute myocardial damage appeared to be the same by 99mTc-PPi scintigram as by ECG; in two, the location could not be precisely determined. The two patients with negative 99mTc-PPi scintigrams at the time of combined myocardial imaging had had positive 99mTc-PPi images previously. In all 24 patients, the 201Tl images were abnormal in at least the location suggested by the electrocardiogram. In seven patients, the area of decreased 201Tl activity was grossly equal to the positive area on the 99mTc-PPi images; in 15, the 201Tl defect was definitely larger; and in two, the 201Tl defect appeared slightly smaller. Although the 99mTc-PPi and 201Tl myocardial images provide different information, both are valuable in determining the overall integrity of the myocardium in patients with ischemic heart disease.", "contents": "Acute myocardial infarction imaged with 99mTc-stannous pyrophosphate and 201Tl: a clinical evaluation. Twenty-six patients suspected of having acute myocardial infarction (AMI) underwent myocardial scintigraphy sequentially with 201Tl and 99mTc-stannous pyrophosphate (99mTc-PPi). Of the 26 patients, 24 had AMI documented by enzyme and electrocardiographic changes. Nineteen had transmural and five had subendocardial myocardial infarctions. The remaining two patients had \"unstable angina pectoris.\" The mean time from onset to imaging was 4 days. Of the 24 patients with AMI, 22 had positive 99mTc-PPi scintigrams. In 20 the area of acute myocardial damage appeared to be the same by 99mTc-PPi scintigram as by ECG; in two, the location could not be precisely determined. The two patients with negative 99mTc-PPi scintigrams at the time of combined myocardial imaging had had positive 99mTc-PPi images previously. In all 24 patients, the 201Tl images were abnormal in at least the location suggested by the electrocardiogram. In seven patients, the area of decreased 201Tl activity was grossly equal to the positive area on the 99mTc-PPi images; in 15, the 201Tl defect was definitely larger; and in two, the 201Tl defect appeared slightly smaller. Although the 99mTc-PPi and 201Tl myocardial images provide different information, both are valuable in determining the overall integrity of the myocardium in patients with ischemic heart disease."} {"id": "PMID:182928", "title": "Melanotic neuroectodermal tumors of the brain and skull.", "content": "A case of melanotic neuroectodermal tumor in the cerebellum of a 21-year-old man is presented. Melanin was found mainly in small neoplastic cells rather than in large epithelioid cells. The tumor also contained neurons, as well as neoplastic tissue of ependyma, choroid plexus; and astrocytes. We propose that this neuroectodermal tumor resulted from a combination of cells originating in the neural crest and in the neural tube. The small cells have been described as medulloblasts, but they may be poorly differentiated ependymal cells, or, sympathicoblasts. The presence of pigment in these cells is compatible with an origin in the neural crest. The so-called melanotic progonoma, occurring most often in the maxilla of infants, is reviewed in relation to the melanotic neuroectodermal tumor of the brain. The tumor in facial bone occurs in adults as well as infants, in locations other than the maxilla, and has malignant forms. Melanotic neuroectodermal tumors, whether in brain or bone, are therefore similar in behavior as well as histologic appearance. The finding of similar tumors in these different locations is readily explained embryologically.", "contents": "Melanotic neuroectodermal tumors of the brain and skull. A case of melanotic neuroectodermal tumor in the cerebellum of a 21-year-old man is presented. Melanin was found mainly in small neoplastic cells rather than in large epithelioid cells. The tumor also contained neurons, as well as neoplastic tissue of ependyma, choroid plexus; and astrocytes. We propose that this neuroectodermal tumor resulted from a combination of cells originating in the neural crest and in the neural tube. The small cells have been described as medulloblasts, but they may be poorly differentiated ependymal cells, or, sympathicoblasts. The presence of pigment in these cells is compatible with an origin in the neural crest. The so-called melanotic progonoma, occurring most often in the maxilla of infants, is reviewed in relation to the melanotic neuroectodermal tumor of the brain. The tumor in facial bone occurs in adults as well as infants, in locations other than the maxilla, and has malignant forms. Melanotic neuroectodermal tumors, whether in brain or bone, are therefore similar in behavior as well as histologic appearance. The finding of similar tumors in these different locations is readily explained embryologically."} {"id": "PMID:182931", "title": "Radionuclide bone-scan abnormalities in leprosy: case reports.", "content": "Radionuclide bone scans were performed on two patients with leprosy. The resulting scan patterns simulated hypertrophic osteoarthropathy and diffuse arthritis, findings entirely consistent with the primary disease process.", "contents": "Radionuclide bone-scan abnormalities in leprosy: case reports. Radionuclide bone scans were performed on two patients with leprosy. The resulting scan patterns simulated hypertrophic osteoarthropathy and diffuse arthritis, findings entirely consistent with the primary disease process."} {"id": "PMID:182932", "title": "99mTc-pyrophosphate scan and radiographic correlation in thyroid acropachy: case report.", "content": "A case of thyroid acropachy secondary to Graves' disease is described. Radiographic abnormalities were found to correlate with those in a 99mTc-pyrophosphate bone scan. Abnormal tracer concentrations were observed in the diaphyses of the metacarpals and phalanges of both hands and also in regions of pretibial myxedema. The differential diagnosis of the scan abnormalities is discussed.", "contents": "99mTc-pyrophosphate scan and radiographic correlation in thyroid acropachy: case report. A case of thyroid acropachy secondary to Graves' disease is described. Radiographic abnormalities were found to correlate with those in a 99mTc-pyrophosphate bone scan. Abnormal tracer concentrations were observed in the diaphyses of the metacarpals and phalanges of both hands and also in regions of pretibial myxedema. The differential diagnosis of the scan abnormalities is discussed."} {"id": "PMID:182933", "title": "Rapid determination of oxidation state of unbound 99mTc and labeling yield in 99mTc-labeled radiopharmaceuticals.", "content": "Current techniques for determining the radiochemical purity of 99mTc-labeled radiopharmaceuticals are limited by the variety of compounds that can be tested or the length of time required to complete the test. A chromatographic method, based on the use of two solvents (0.9% saline and acetone) and a stationary phase made of silica-coated cellulose strips, solves these problems for water-soluble 99mTc-labeled radiopharmaceuticals. With this method, the oxidation state of unbound 99mTc and the labeling yield of 99mTc-labeled radiopharmaceuticals can be quickly determined: the whole procedure takes only a few minutes to run. This system compares favorably with lengthier procedures and with a commercially available kit.", "contents": "Rapid determination of oxidation state of unbound 99mTc and labeling yield in 99mTc-labeled radiopharmaceuticals. Current techniques for determining the radiochemical purity of 99mTc-labeled radiopharmaceuticals are limited by the variety of compounds that can be tested or the length of time required to complete the test. A chromatographic method, based on the use of two solvents (0.9% saline and acetone) and a stationary phase made of silica-coated cellulose strips, solves these problems for water-soluble 99mTc-labeled radiopharmaceuticals. With this method, the oxidation state of unbound 99mTc and the labeling yield of 99mTc-labeled radiopharmaceuticals can be quickly determined: the whole procedure takes only a few minutes to run. This system compares favorably with lengthier procedures and with a commercially available kit."} {"id": "PMID:182929", "title": "A case of human rabies and ultrastructure of the Negri body.", "content": "A 60-year old man, eight weeks after being bitten on his finger by a stray cat, developed symptoms and signs of rabies which progressed rapidly over the next two weeks and he died of respiratory failure. Pathological examination revealed characteristic cytoplasmic inclusions in neurons of various parts of the central nervous system and the dorsal spinal and sympathetic ganglia. The diagnosis of rabies was confirmed by direct fluorescent antibody staining of the brain tissue obtained at autopsy. On histological examination, most, if not all, of the neuronal cytoplasmic inclusions were eosinophilic and homogeneous and lacked the basophilic inner granules or bodies characteristic of Negri bodies. Nevertheless, they were ultrastructurally identical with Negri bodies by virtue of being made up of finely fibrillar matrix and virus and/or related particles in varying numbers. This indicates that ultrastructurally typica Negri bodies may or may not have the histologically visible basophilic inner bodies depending upon the degree of virus replication. In light of the ultrastructural evidence, lyssa bodies described in rabies in the past may represent Negri bodies without histologically recognizable inner bodies or cytoplasmic inclusions unrelated to rabies, occurring ordinarily in normal or degenerating neurons. It is, therefore, suggested that the term, lyssa body, is obsolete and should no longer be used.", "contents": "A case of human rabies and ultrastructure of the Negri body. A 60-year old man, eight weeks after being bitten on his finger by a stray cat, developed symptoms and signs of rabies which progressed rapidly over the next two weeks and he died of respiratory failure. Pathological examination revealed characteristic cytoplasmic inclusions in neurons of various parts of the central nervous system and the dorsal spinal and sympathetic ganglia. The diagnosis of rabies was confirmed by direct fluorescent antibody staining of the brain tissue obtained at autopsy. On histological examination, most, if not all, of the neuronal cytoplasmic inclusions were eosinophilic and homogeneous and lacked the basophilic inner granules or bodies characteristic of Negri bodies. Nevertheless, they were ultrastructurally identical with Negri bodies by virtue of being made up of finely fibrillar matrix and virus and/or related particles in varying numbers. This indicates that ultrastructurally typica Negri bodies may or may not have the histologically visible basophilic inner bodies depending upon the degree of virus replication. In light of the ultrastructural evidence, lyssa bodies described in rabies in the past may represent Negri bodies without histologically recognizable inner bodies or cytoplasmic inclusions unrelated to rabies, occurring ordinarily in normal or degenerating neurons. It is, therefore, suggested that the term, lyssa body, is obsolete and should no longer be used."} {"id": "PMID:182936", "title": "Effect of dietary fat on hepatic metabolism of 14C-oleic acid and very low density lipoprotein triglyceride in the gerbil.", "content": "In order to compare in vitro and in vivo aspects of lipid metabolism and lipoprotein secretion associated with the hyperlipemia of saturated fat feeding, gerbils were fed a diet containing 15% coconut oil or safflower oil for 6 weeks. In vitro incorporation of fatty acid was determined by measuring 14C-oleic acid incorporation into hepatic lipis in liver fasting gerbils following Triton WR1339 injection. The plasma lipoprotein profile was assessed by agarose electrophoresis. Coconut oil produced a hypertriglyceridemia and hypercholesterolemia associated with the appearance of very low density migrating lipoprotein, not seen with the safflower oil. Coconut oil also increased the hepatic triglyceride content, enhanced 14C-oleic acid incorporation into total lipid, and favored fatty acid incorporation into triglyceride; safflower oil facilitated esterification of oleic acid into phospholipid. Triton blockade of gerbils fed safflower oil resulted in twice the triglyceride secretion rate of those fed coconut oil. Our interpretation of the data is that dietary polyunsaturated fat favors incorporation of fatty acids into phospholipid, enhances both triglyceride secretion and the plasma transport and clearance of triglyceride and cholesterol and that the hyperlipemia of coconut oil feeding reflects a reduced metabolic clearnace of circulating lipid associated with that dietary fat.", "contents": "Effect of dietary fat on hepatic metabolism of 14C-oleic acid and very low density lipoprotein triglyceride in the gerbil. In order to compare in vitro and in vivo aspects of lipid metabolism and lipoprotein secretion associated with the hyperlipemia of saturated fat feeding, gerbils were fed a diet containing 15% coconut oil or safflower oil for 6 weeks. In vitro incorporation of fatty acid was determined by measuring 14C-oleic acid incorporation into hepatic lipis in liver fasting gerbils following Triton WR1339 injection. The plasma lipoprotein profile was assessed by agarose electrophoresis. Coconut oil produced a hypertriglyceridemia and hypercholesterolemia associated with the appearance of very low density migrating lipoprotein, not seen with the safflower oil. Coconut oil also increased the hepatic triglyceride content, enhanced 14C-oleic acid incorporation into total lipid, and favored fatty acid incorporation into triglyceride; safflower oil facilitated esterification of oleic acid into phospholipid. Triton blockade of gerbils fed safflower oil resulted in twice the triglyceride secretion rate of those fed coconut oil. Our interpretation of the data is that dietary polyunsaturated fat favors incorporation of fatty acids into phospholipid, enhances both triglyceride secretion and the plasma transport and clearance of triglyceride and cholesterol and that the hyperlipemia of coconut oil feeding reflects a reduced metabolic clearnace of circulating lipid associated with that dietary fat."} {"id": "PMID:182937", "title": "Effects in the rat of environmental temperature, diet dilution, and treadmill running on liver and adipose enzymes and metabolism of 14C-glucose: a multiple regression analysis.", "content": "The effects of two environmental temperatures (T; 16 degrees and 31 degrees), five diet dilutions (D; 0%, 12.5%, 25%, 37.5% and 50%), and five daily treadmill running periods (E; 10 minutes, 40 minutes, 70 minutes, 100 minutes, and 130 minutes) upon enzyme activities of liver and adipose tissue of male rats were observed. Liver enzymes studied were glucose-6-phosphatase (G6Pase), 6-P-gluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fructose diphosphatase (FDPase), NADP-isocitrate dehydrogenase (ICDH), and malic enzyme (ME). Adipose tissue (epididymal fat) enzymes (6PGD, G6PD, and ME) were studied as well as the in vitro incorporation of the 14C of [U-14C] glucose into liberated 14CO2 and into the triglycerides, free fatty acids, and total lipids by adipose tissue slices. Equations describing regression surfaces for these responses (expressed as units/100 g body weight) could contain significant linear coefficients of the independent variables (T, D, and E), their first order interactions, and quadratic coefficients for D and E. Significnat regression coefficients for activities of liver enzymes associated with increased lipogenesis (6PGD, G6PD, and ME) produced response surfaces with conformations generally concave downward. All enzymes possessed positive and negative linear and quadratic coefficients for D which caused response surfaces to be concave downward with respect to that variable. Also, 6PGD and G6PD (positive linear and negative quadratic coefficients for E) exhibited response surfaces concave downward with respect to E. Additionally, 6PGD showed greater activity at 31 degrees than at 16 degrees while G6PD showed no effect of temperature on activity. Liver ICDH, probably important in supplying reducing equivalents for fatty acid synthesis, evidenced response surfaces almost identical to those for 6PGD. Significant regression coefficients for activity of liver enzymes associated with increased gluconeogenesis (FDPase and G6Pase) produced for FDPase a response surface concave downward with respect to both D and E with greater values at 31 degrees than at 16 degrees; but for G6Pase non-concave surfaces with lesser values at 31 degrees than at 16 degrees. Significant regression coefficients for activities of adipose enzymes associated with increased lipogenesis produced for 6PGD a response surface concave upward due to negative linear and positive quadratic coefficients for both D and E. For G6PD and ME regression surfaces were concave upward with respect to E, but these were modified by positive and negative linear coefficients, respectively, for D. Significant regression coefficients for incorporation of the 14C of glucose into triglycerides and free fatty acids of adipose tissue slices and their production of 14CO2 yielded response surfaces concave upward with respect to E (negative linear and positive quadratic coefficients). In addition, the surface for free fatty acids was concave upward with respect to D. The 14CO2 production was greater at 16 degrees than at 31 degrees...", "contents": "Effects in the rat of environmental temperature, diet dilution, and treadmill running on liver and adipose enzymes and metabolism of 14C-glucose: a multiple regression analysis. The effects of two environmental temperatures (T; 16 degrees and 31 degrees), five diet dilutions (D; 0%, 12.5%, 25%, 37.5% and 50%), and five daily treadmill running periods (E; 10 minutes, 40 minutes, 70 minutes, 100 minutes, and 130 minutes) upon enzyme activities of liver and adipose tissue of male rats were observed. Liver enzymes studied were glucose-6-phosphatase (G6Pase), 6-P-gluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fructose diphosphatase (FDPase), NADP-isocitrate dehydrogenase (ICDH), and malic enzyme (ME). Adipose tissue (epididymal fat) enzymes (6PGD, G6PD, and ME) were studied as well as the in vitro incorporation of the 14C of [U-14C] glucose into liberated 14CO2 and into the triglycerides, free fatty acids, and total lipids by adipose tissue slices. Equations describing regression surfaces for these responses (expressed as units/100 g body weight) could contain significant linear coefficients of the independent variables (T, D, and E), their first order interactions, and quadratic coefficients for D and E. Significnat regression coefficients for activities of liver enzymes associated with increased lipogenesis (6PGD, G6PD, and ME) produced response surfaces with conformations generally concave downward. All enzymes possessed positive and negative linear and quadratic coefficients for D which caused response surfaces to be concave downward with respect to that variable. Also, 6PGD and G6PD (positive linear and negative quadratic coefficients for E) exhibited response surfaces concave downward with respect to E. Additionally, 6PGD showed greater activity at 31 degrees than at 16 degrees while G6PD showed no effect of temperature on activity. Liver ICDH, probably important in supplying reducing equivalents for fatty acid synthesis, evidenced response surfaces almost identical to those for 6PGD. Significant regression coefficients for activity of liver enzymes associated with increased gluconeogenesis (FDPase and G6Pase) produced for FDPase a response surface concave downward with respect to both D and E with greater values at 31 degrees than at 16 degrees; but for G6Pase non-concave surfaces with lesser values at 31 degrees than at 16 degrees. Significant regression coefficients for activities of adipose enzymes associated with increased lipogenesis produced for 6PGD a response surface concave upward due to negative linear and positive quadratic coefficients for both D and E. For G6PD and ME regression surfaces were concave upward with respect to E, but these were modified by positive and negative linear coefficients, respectively, for D. Significant regression coefficients for incorporation of the 14C of glucose into triglycerides and free fatty acids of adipose tissue slices and their production of 14CO2 yielded response surfaces concave upward with respect to E (negative linear and positive quadratic coefficients). In addition, the surface for free fatty acids was concave upward with respect to D. The 14CO2 production was greater at 16 degrees than at 31 degrees..."} {"id": "PMID:182938", "title": "Regulation of intestinal calcium absorption in the laying quail: independent of kidney vitamin D hydroxylation.", "content": "Two experiments were carried out with laying quail (Coturnix coturnix japonica) fed either cholecalciferol (40 mug/kg) or 1 alpha-hydroxycholecalciferol (8 mug/kg). Recovery following vitamin D depletion, as indicated by egg production and shell deposition, was faster in quail fed 1 alpha-hydroxycholecalciferol than in those fed cholecalciferol. Overall intestinal calcium absorption was higher in the 1 alpha-hydroxycholecalciferol-fed quail due to a higher absorption in the middle parts of the small intestine. This was associated with corresponding differences in the concentration of calcium binding protein. Intestinal calcium absorption was markedly higher during periods of shell formation than during periods of uterine inactivity in quail fed either cholecalciferol or 1 alpha-hydroxycholecalciferol. It is suggested, therefore, that the mechanism responsible for this difference is independent of vitamin D hydroxylation in the kidney.", "contents": "Regulation of intestinal calcium absorption in the laying quail: independent of kidney vitamin D hydroxylation. Two experiments were carried out with laying quail (Coturnix coturnix japonica) fed either cholecalciferol (40 mug/kg) or 1 alpha-hydroxycholecalciferol (8 mug/kg). Recovery following vitamin D depletion, as indicated by egg production and shell deposition, was faster in quail fed 1 alpha-hydroxycholecalciferol than in those fed cholecalciferol. Overall intestinal calcium absorption was higher in the 1 alpha-hydroxycholecalciferol-fed quail due to a higher absorption in the middle parts of the small intestine. This was associated with corresponding differences in the concentration of calcium binding protein. Intestinal calcium absorption was markedly higher during periods of shell formation than during periods of uterine inactivity in quail fed either cholecalciferol or 1 alpha-hydroxycholecalciferol. It is suggested, therefore, that the mechanism responsible for this difference is independent of vitamin D hydroxylation in the kidney."} {"id": "PMID:182939", "title": "Gas-liquid chromatographic determination of vitamin D in multivitamin preparation.", "content": "Gas-liquid chromatographic (GLC) determination of vitamin D in multivitamin preparations was investigated and a simple routine method was established. The unsaponifiable matters of a sample was applied to a thin-layer chromatography (TLC) plate using Kieselgel GF254 as an adsorbent and a mixture of n-hexane-ethyl acetate (4:1) as a developing solvent. The scraped zones corresponding to vitamin D and previtamin D were extracted and determined by GLC using 1.5% OV-17 packed on Shimalite W (80-100 mesh) as a stationary phase. When the proposed method was applied to model preparations made by mixing vitamin D, A and E, it was confirmed that the determination of vitamin D was possible when the ratios of vitamin A and E (DL-alpha-tocopheryl acetate) to vitamin D were within 104 (I.U. ratio) and 2,500 (weight ratio), respectively. Since the ratios of most of commercial multivitamin preparations on sale in Japan are within the limitations and the results on multivitamin preparations were also satisfactory, the proposed method was confirmed to be suitable simple routine.", "contents": "Gas-liquid chromatographic determination of vitamin D in multivitamin preparation. Gas-liquid chromatographic (GLC) determination of vitamin D in multivitamin preparations was investigated and a simple routine method was established. The unsaponifiable matters of a sample was applied to a thin-layer chromatography (TLC) plate using Kieselgel GF254 as an adsorbent and a mixture of n-hexane-ethyl acetate (4:1) as a developing solvent. The scraped zones corresponding to vitamin D and previtamin D were extracted and determined by GLC using 1.5% OV-17 packed on Shimalite W (80-100 mesh) as a stationary phase. When the proposed method was applied to model preparations made by mixing vitamin D, A and E, it was confirmed that the determination of vitamin D was possible when the ratios of vitamin A and E (DL-alpha-tocopheryl acetate) to vitamin D were within 104 (I.U. ratio) and 2,500 (weight ratio), respectively. Since the ratios of most of commercial multivitamin preparations on sale in Japan are within the limitations and the results on multivitamin preparations were also satisfactory, the proposed method was confirmed to be suitable simple routine."} {"id": "PMID:182940", "title": "Formation of guanine ribonucleotidyl-(3'-5')-adenosine in a flavinogenic strain of Eremothecium ashbyii.", "content": "The addition of caffeine caused the accumulation of a new nucleotide compound simultaneously with the rigid inhibition of ribofalvin production in non-growing cells of Eremothecium ashbyii. In the present study we tried to identify the structure of the nucleotide compound using non-growing cells of the mold. 1) It became possible to obtain a large amount of mycelia by masscultivation in a reagent tank. 2) A new nucleotide compound, referred to as compound A in the paper, was extracted with perchloric acid solution and purified by the following subsequent procedures: 1) Dowex 1 x 2 (HCOO-) column, 2) charcoal treatment, 3) DEAE-Sephadex A25 (CI-) column, 4) Dowex 1 x 2 (C1-) column, and 5) DEAE-Sephadex A25 (HCO3-) column. 3) The structure of the new nucleotide compound was proved to be guanine ribonucleotidyl-(3'-5')-adenosine (GpA) from the results of the following analyses: 1) alkaline degradation, 2) UV-spectra, IR-spectra and NMR-spectra, and 3) enzymatic treatments with RNase T2 and phosphodiesterase. 4) The roles of caffeine and guanine ribonucleotidyl-(3'-5')-adenosine in connection with flavinogenesis of this mold were discussed.", "contents": "Formation of guanine ribonucleotidyl-(3'-5')-adenosine in a flavinogenic strain of Eremothecium ashbyii. The addition of caffeine caused the accumulation of a new nucleotide compound simultaneously with the rigid inhibition of ribofalvin production in non-growing cells of Eremothecium ashbyii. In the present study we tried to identify the structure of the nucleotide compound using non-growing cells of the mold. 1) It became possible to obtain a large amount of mycelia by masscultivation in a reagent tank. 2) A new nucleotide compound, referred to as compound A in the paper, was extracted with perchloric acid solution and purified by the following subsequent procedures: 1) Dowex 1 x 2 (HCOO-) column, 2) charcoal treatment, 3) DEAE-Sephadex A25 (CI-) column, 4) Dowex 1 x 2 (C1-) column, and 5) DEAE-Sephadex A25 (HCO3-) column. 3) The structure of the new nucleotide compound was proved to be guanine ribonucleotidyl-(3'-5')-adenosine (GpA) from the results of the following analyses: 1) alkaline degradation, 2) UV-spectra, IR-spectra and NMR-spectra, and 3) enzymatic treatments with RNase T2 and phosphodiesterase. 4) The roles of caffeine and guanine ribonucleotidyl-(3'-5')-adenosine in connection with flavinogenesis of this mold were discussed."} {"id": "PMID:182943", "title": "The incidence, pathology and transplantation of hepatomas in CBA mice.", "content": "Two hundred and seventy-five male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied at intervals over the whole range of their natural life span of about 2 1/2 yr. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight then decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were very prominent, suggestive of an on-going immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all the mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear plemorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumour metastasised to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1-6 wk (range 1-3-1-8 wk). These hepatomas were transplantable and grew with a doubling of 2-25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumour in situ in old CBA mice might have resulted from a breakdown in \"immunological surveillance\" the same tumour was transplanted simultaneously to a group of young and old recipients. The tumour grew more slowly (doubling time, 2-5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumours in situ in old mice.", "contents": "The incidence, pathology and transplantation of hepatomas in CBA mice. Two hundred and seventy-five male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied at intervals over the whole range of their natural life span of about 2 1/2 yr. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight then decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were very prominent, suggestive of an on-going immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all the mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear plemorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumour metastasised to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1-6 wk (range 1-3-1-8 wk). These hepatomas were transplantable and grew with a doubling of 2-25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumour in situ in old CBA mice might have resulted from a breakdown in \"immunological surveillance\" the same tumour was transplanted simultaneously to a group of young and old recipients. The tumour grew more slowly (doubling time, 2-5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumours in situ in old mice."} {"id": "PMID:182944", "title": "Studies in a phenotypic female with 17-alpha-hydroxylase deficiency.", "content": "In a 19-year-old phenotypic female (46, XY) with hypertension and hypokalemia, studies confirmed 17-alpha-hydroxylase deficiency. Prior to diagnosis she had been considered to have testicular feminization. Increased plasma progesterone and urinary pregnanediol levels were present before treatment. Increased secretion rates of deoxycorticosterone and corticosterone and abnormally low production of cortisol and aldosterone were present. Following treatment with hydrocortisone, plasma progesterone, serum potassium, and urinary pregnanediol levels and DOC and B secretions were normal. Aldosterone secretion six months after treatment remained low. Normal blood pressure measurements were achieved during treatment with hydrocortisone and oral estrogen with the patient at rest; however, mild elevations in blood pressure (130/90 mm Hg) have been noted despite continued hydrocortisone therapy.", "contents": "Studies in a phenotypic female with 17-alpha-hydroxylase deficiency. In a 19-year-old phenotypic female (46, XY) with hypertension and hypokalemia, studies confirmed 17-alpha-hydroxylase deficiency. Prior to diagnosis she had been considered to have testicular feminization. Increased plasma progesterone and urinary pregnanediol levels were present before treatment. Increased secretion rates of deoxycorticosterone and corticosterone and abnormally low production of cortisol and aldosterone were present. Following treatment with hydrocortisone, plasma progesterone, serum potassium, and urinary pregnanediol levels and DOC and B secretions were normal. Aldosterone secretion six months after treatment remained low. Normal blood pressure measurements were achieved during treatment with hydrocortisone and oral estrogen with the patient at rest; however, mild elevations in blood pressure (130/90 mm Hg) have been noted despite continued hydrocortisone therapy."} {"id": "PMID:182946", "title": "Leukocyte transforming agent (Epstein-Barr virus) in newborn infants and older individuals.", "content": "The lymphocyte transforming agent, associated with Epstein-Barr virus, was sought in the oropharynx and other clinical sites of 443 individuals in the following groups: premature and term neonates; infants with congenital malformations or with suspected TORCH syndrome; children with various illnesses; pregnant and postpartum women; healthy adults; and patients with infectious mononucleosis. Evidence of intrauterine infection was found in one newborn infant and LTA was demonstrated in a 16-day-old infant who developed transient hepatosplenomegaly. LTA was not detected in 96 other newborn infants and 57 infants with various anomalies or illnesses; nor was it found in the cervix of 125 pregnant or postpartum women. LTA was demonstrated in varying frequency in ill children, healthy adults, and those with infectious mononucleosis. It is suggested that the clinicoepidemiologic patterns of EBV infection in newborn infants and children will best be established by prospective studies.", "contents": "Leukocyte transforming agent (Epstein-Barr virus) in newborn infants and older individuals. The lymphocyte transforming agent, associated with Epstein-Barr virus, was sought in the oropharynx and other clinical sites of 443 individuals in the following groups: premature and term neonates; infants with congenital malformations or with suspected TORCH syndrome; children with various illnesses; pregnant and postpartum women; healthy adults; and patients with infectious mononucleosis. Evidence of intrauterine infection was found in one newborn infant and LTA was demonstrated in a 16-day-old infant who developed transient hepatosplenomegaly. LTA was not detected in 96 other newborn infants and 57 infants with various anomalies or illnesses; nor was it found in the cervix of 125 pregnant or postpartum women. LTA was demonstrated in varying frequency in ill children, healthy adults, and those with infectious mononucleosis. It is suggested that the clinicoepidemiologic patterns of EBV infection in newborn infants and children will best be established by prospective studies."} {"id": "PMID:182947", "title": "Evaluation of a walking-donor blood transfusion program in an intensive care nursery.", "content": "A prospective study was carried out to identify the immediate and long-range advantages and disadvantages of a walking-donor transfusion program for an intensive care newborn nursery. The effect of heparin on coagulation of blood was evaluated and found to be minimal. There was no evidence of transmission of HBSAg. The prevalence of CMV infection at the time of follow-up was higher in infants who had received blood from donors seropositive for CMV than in infants who had been transfused from seronegative donors. In our experience, a walking-donor program has been a safe and effective method for the provision of small transfusions of blood to sick neonates.", "contents": "Evaluation of a walking-donor blood transfusion program in an intensive care nursery. A prospective study was carried out to identify the immediate and long-range advantages and disadvantages of a walking-donor transfusion program for an intensive care newborn nursery. The effect of heparin on coagulation of blood was evaluated and found to be minimal. There was no evidence of transmission of HBSAg. The prevalence of CMV infection at the time of follow-up was higher in infants who had received blood from donors seropositive for CMV than in infants who had been transfused from seronegative donors. In our experience, a walking-donor program has been a safe and effective method for the provision of small transfusions of blood to sick neonates."} {"id": "PMID:182948", "title": "Overdosage with vincristine.", "content": "Five patients received overdoses of vincristine ranging from 3.5 to 32 mg. Neurotoxicity accounted for most of the complications observed. Peripheral neuropathies, cranial nerve palsies, paralytic ileus, atony of the bladder, hypertension, hypotension, seizures, inappropriate ADH secretion, and severe bone marrow depression were all encountered. Two patients died within 72 hours of the overdose. Another patient died of sepsis 22 days after the overdose. Two patients recovered and were discharged. The three patients who survived longer than a few days showed improvement in the vincristine-induced neuropathy, and the two long-term survivors had essentially complete recovery. It appears that if a patient can be supported through the critical period following an overdose, he can be expected to recover normal neurologic function.", "contents": "Overdosage with vincristine. Five patients received overdoses of vincristine ranging from 3.5 to 32 mg. Neurotoxicity accounted for most of the complications observed. Peripheral neuropathies, cranial nerve palsies, paralytic ileus, atony of the bladder, hypertension, hypotension, seizures, inappropriate ADH secretion, and severe bone marrow depression were all encountered. Two patients died within 72 hours of the overdose. Another patient died of sepsis 22 days after the overdose. Two patients recovered and were discharged. The three patients who survived longer than a few days showed improvement in the vincristine-induced neuropathy, and the two long-term survivors had essentially complete recovery. It appears that if a patient can be supported through the critical period following an overdose, he can be expected to recover normal neurologic function."} {"id": "PMID:182950", "title": "Management of breast lesions in children and adolescents.", "content": "The records of 207 patients evaluated and treated for breast abnormalities during a 10-yr period were reviewed. Patients ranged in age from 1 wk through 16 yr. Seventy-eight per cent were female. Operative procedures were performed in 134 patients (64%). Most common diagnoses were fibroadenoma, premature thelarche, and precocious puberty in the females, and pubertal gynecomastia in the males. Age and sex separate patients into natural subgroups. In females beyond the neonatal period, premature thelarche and precocious puberty are the most likely cause of breast enlargement. Breast biopsy is only rarely indicated for a distinct mass lesion in the prepubertal breast. Mass lesions in the breast of adolescent females require excisional biopsy. In the male, pubertal gynecomastia is the most common form of breast enlargement and only occasionally requires subcutaneous mastectomy for cosmetic and psychologic reasons. Careful evaluation of all children with breast enlargement is indicated to uncover underlying causes and to avoid unnecessary operative procedures.", "contents": "Management of breast lesions in children and adolescents. The records of 207 patients evaluated and treated for breast abnormalities during a 10-yr period were reviewed. Patients ranged in age from 1 wk through 16 yr. Seventy-eight per cent were female. Operative procedures were performed in 134 patients (64%). Most common diagnoses were fibroadenoma, premature thelarche, and precocious puberty in the females, and pubertal gynecomastia in the males. Age and sex separate patients into natural subgroups. In females beyond the neonatal period, premature thelarche and precocious puberty are the most likely cause of breast enlargement. Breast biopsy is only rarely indicated for a distinct mass lesion in the prepubertal breast. Mass lesions in the breast of adolescent females require excisional biopsy. In the male, pubertal gynecomastia is the most common form of breast enlargement and only occasionally requires subcutaneous mastectomy for cosmetic and psychologic reasons. Careful evaluation of all children with breast enlargement is indicated to uncover underlying causes and to avoid unnecessary operative procedures."} {"id": "PMID:182951", "title": "Treatment of heterozygous type II hyperlipidemia by partial ileal bypass in a pediatric population.", "content": "Nine patients underwent partial ileal bypass as management for heterozygous type II hyperlipidemia. The average age of this group was 12.5 yr. Follow-up has ranged from 1 to 6 yr. The growth and development of these children proceeded normally. The overall average serum cholesterol reduction was 33% when compared to the preoperative but postdietary control value. Side effects of the procedure include transient diarrhea and inability to absorb vitamin B12, requiring periodic parenteral administration. Partial ileal bypass has been shown to be an effective and obligatory method of treatment of hypercholesterolemia in children.", "contents": "Treatment of heterozygous type II hyperlipidemia by partial ileal bypass in a pediatric population. Nine patients underwent partial ileal bypass as management for heterozygous type II hyperlipidemia. The average age of this group was 12.5 yr. Follow-up has ranged from 1 to 6 yr. The growth and development of these children proceeded normally. The overall average serum cholesterol reduction was 33% when compared to the preoperative but postdietary control value. Side effects of the procedure include transient diarrhea and inability to absorb vitamin B12, requiring periodic parenteral administration. Partial ileal bypass has been shown to be an effective and obligatory method of treatment of hypercholesterolemia in children."} {"id": "PMID:182953", "title": "High-performance liquid chromatographic analysis of vitamins I: quantitation of cholecalciferol or ergocalciferol in presence of photochemical isomers of the provitamin and application to cholecalciferol resins.", "content": "A high-performance liquid chromatographic (HPLC) procedure was developed for the quantitative determination of cholecalciferol or ergocalciferol in the presence of the photochemical isomers of the provitamin. Separation is also achieved from various common reaction products encountered in the vitamin synthesis as well as other fat-soluble vitamins. The method was applied to the routine analysis of cholecalciferol resins, and experimental data are set forth. A comparison of the HPLC method to the AOAC biological and chemical procedures shows that the HPLC method most closely approximates the antirachitic activity of a cholecalciferol sample. The specificity, sensitivity, and reproducibility of the method make it applicable to various vitamin samples containing cholecalciferol or ergocalciferol.", "contents": "High-performance liquid chromatographic analysis of vitamins I: quantitation of cholecalciferol or ergocalciferol in presence of photochemical isomers of the provitamin and application to cholecalciferol resins. A high-performance liquid chromatographic (HPLC) procedure was developed for the quantitative determination of cholecalciferol or ergocalciferol in the presence of the photochemical isomers of the provitamin. Separation is also achieved from various common reaction products encountered in the vitamin synthesis as well as other fat-soluble vitamins. The method was applied to the routine analysis of cholecalciferol resins, and experimental data are set forth. A comparison of the HPLC method to the AOAC biological and chemical procedures shows that the HPLC method most closely approximates the antirachitic activity of a cholecalciferol sample. The specificity, sensitivity, and reproducibility of the method make it applicable to various vitamin samples containing cholecalciferol or ergocalciferol."} {"id": "PMID:182956", "title": "Kinetics and energetics of calcium efflux from intact squid giant axons.", "content": "The Ca efflux from intact squid axons consists of three major components: one that is activated by Cao, one that is activated by Nao and a residual flux that persists in the nominal absence of both Cao and Nao. The properties of these components have been investigated in unpoisoned axons and in axons poisoned with cyanide. 2. Under all conditions the shape of the curve relating Cao to Cao-activated Ca efflux approximates to a section of a rectangular hyperbola, consistent with simple Michaelis activation. 3. The external Ca concentration giving half-maximal activation of Cao-activated Ca efflux is about 2 muM in unpoisoned axons immersed in Na-ASW, but on poisoning changes progressively to values in the range 1-10 mM. The residual efflux from unpoisoned axons may reflect activation by traces of Ca present immediately external to the axolemma. 4. The apparent affinity for Cao of Cao-activated Ca efflux is very similar in unpoisoned axons immersed in sea waters containing Na, Li, Tris or K as major cation, whereas in poisoned axons the affinity in Na and Li is about the same but higher than that in choline and Tris. 5. In unpoisoned axons Ca influx increases linearly as Cao is increased from 2 muM to 110 mM. The absolute value of the Ca influx from 10 muM-Cao is less than 1% of the Cao-activated Ca efflux at this external Ca concentration. In poisoned axons the sizes of Cao-activated Ca efflux and Ca influx were similar at all Ca concentrations examined. 6. The shape of the curve relating Nao to Nao-activated Ca efflux approximates to a section of rectangular hyperbola in unpoisoned axons but is clearly sigmoidal in axons that have been fully poisoned with cyanide. The sigmoidal shape develops progressively during poisoning. ...", "contents": "Kinetics and energetics of calcium efflux from intact squid giant axons. The Ca efflux from intact squid axons consists of three major components: one that is activated by Cao, one that is activated by Nao and a residual flux that persists in the nominal absence of both Cao and Nao. The properties of these components have been investigated in unpoisoned axons and in axons poisoned with cyanide. 2. Under all conditions the shape of the curve relating Cao to Cao-activated Ca efflux approximates to a section of a rectangular hyperbola, consistent with simple Michaelis activation. 3. The external Ca concentration giving half-maximal activation of Cao-activated Ca efflux is about 2 muM in unpoisoned axons immersed in Na-ASW, but on poisoning changes progressively to values in the range 1-10 mM. The residual efflux from unpoisoned axons may reflect activation by traces of Ca present immediately external to the axolemma. 4. The apparent affinity for Cao of Cao-activated Ca efflux is very similar in unpoisoned axons immersed in sea waters containing Na, Li, Tris or K as major cation, whereas in poisoned axons the affinity in Na and Li is about the same but higher than that in choline and Tris. 5. In unpoisoned axons Ca influx increases linearly as Cao is increased from 2 muM to 110 mM. The absolute value of the Ca influx from 10 muM-Cao is less than 1% of the Cao-activated Ca efflux at this external Ca concentration. In poisoned axons the sizes of Cao-activated Ca efflux and Ca influx were similar at all Ca concentrations examined. 6. The shape of the curve relating Nao to Nao-activated Ca efflux approximates to a section of rectangular hyperbola in unpoisoned axons but is clearly sigmoidal in axons that have been fully poisoned with cyanide. The sigmoidal shape develops progressively during poisoning. ..."} {"id": "PMID:182957", "title": "The number of sodium ion pumping sites in skeletal muscle and its modification by insulin.", "content": "1. [3H]ouabain binding by frog sartorius muscles shows at least two components: one linked to inhibition of the pump and another not related to transport inhibition. This is suggested by the finding that [3H]ouabain uptake continued to increase when (a) the glycoside concentration was increased beyond that causing maximum transport inhibition, and (b) exposure times longer than those required to produce full inhibition were used. 2. A number of 1600 pumping sites per mum2 of membrane was estimated considering only the cylindrical surface of the muscle. 3. Insulin stimulated the ouabain-sensitive components of 22Na efflux and 134Cs influx. It also increased [3H]ouabain binding to a level of 1-7 times the total resting value. The increases in [3H]ouabain binding and in 22Na efflux followed a similar relationship with respect to insulin concentration. 4. Insulin stimulated the Na pump in muscles whose pumping sites had been inhibited by ouabain and then transferred to a glycoside-free solution. This stimulation was observed before detecting any recovery of the initial pumping activity. 5. When both the resting and the insulin-stimulated 22Na efflux had been blocked by ouabain, an additional dose of insulin, in a ouabain-free solution, had no further effects on 22Na efflux. 6. The effects of insulin were unaffected by cycloheximide or by high concentrations of butyryl derivatives of cyclic AMP and cyclic GMP. 7. We conclude that there are two pools of Na pumping sites in muscle cells: one active and another inactive. Insulin unmasks the inactive pumping sites by a mechanism that is independent of protein synthesis, increases in intracellular [Na] or decreases in intracellular [K].", "contents": "The number of sodium ion pumping sites in skeletal muscle and its modification by insulin. 1. [3H]ouabain binding by frog sartorius muscles shows at least two components: one linked to inhibition of the pump and another not related to transport inhibition. This is suggested by the finding that [3H]ouabain uptake continued to increase when (a) the glycoside concentration was increased beyond that causing maximum transport inhibition, and (b) exposure times longer than those required to produce full inhibition were used. 2. A number of 1600 pumping sites per mum2 of membrane was estimated considering only the cylindrical surface of the muscle. 3. Insulin stimulated the ouabain-sensitive components of 22Na efflux and 134Cs influx. It also increased [3H]ouabain binding to a level of 1-7 times the total resting value. The increases in [3H]ouabain binding and in 22Na efflux followed a similar relationship with respect to insulin concentration. 4. Insulin stimulated the Na pump in muscles whose pumping sites had been inhibited by ouabain and then transferred to a glycoside-free solution. This stimulation was observed before detecting any recovery of the initial pumping activity. 5. When both the resting and the insulin-stimulated 22Na efflux had been blocked by ouabain, an additional dose of insulin, in a ouabain-free solution, had no further effects on 22Na efflux. 6. The effects of insulin were unaffected by cycloheximide or by high concentrations of butyryl derivatives of cyclic AMP and cyclic GMP. 7. We conclude that there are two pools of Na pumping sites in muscle cells: one active and another inactive. Insulin unmasks the inactive pumping sites by a mechanism that is independent of protein synthesis, increases in intracellular [Na] or decreases in intracellular [K]."} {"id": "PMID:182958", "title": "The temperature dependence of the movement of potassium and chloride ions associated with nerve impulses.", "content": "1. The influx and efflux of radioactive potassium and chloride across the membrane of the squid giant axon were measured in resting and in stimulated nerves. The measurements were made at room temperature and at 6-8 degrees C. 2. At room temperature all eight flux measurements were comparable to previously reported values. 3. When the axons were cooled the resting potassium influx decreased with a Q10 of 1-9 and the resting potassium efflux decreased with a Q10 of 1-2. 4. With cooling the resting chloride efflux decreased with a Q10 of 1-3 and the resting chloride influx decreased with a Q10 of 2-8. This latter value, together with anomalous flux ratios for resting chloride fluxes may indicate an active uptake of chloride ions into the axon. 5. Cooling increased the extra efflux of potassium associated with nerve impulses with a Q10 of 1/1-5 and increased the extra influx of potassium with a Q10 of 1/3-3. 6. No extra efflux of chloride was detected at either temperature. Cooling produced no statistically significant change in the extra chloride influx but there was considerable scatter in the data. 7. Fluxes were computed as a function of temperature for standard action potentials with a variety of temperature coefficients for the conductances and rate constants. No single curve could match either the influx or the efflux data.", "contents": "The temperature dependence of the movement of potassium and chloride ions associated with nerve impulses. 1. The influx and efflux of radioactive potassium and chloride across the membrane of the squid giant axon were measured in resting and in stimulated nerves. The measurements were made at room temperature and at 6-8 degrees C. 2. At room temperature all eight flux measurements were comparable to previously reported values. 3. When the axons were cooled the resting potassium influx decreased with a Q10 of 1-9 and the resting potassium efflux decreased with a Q10 of 1-2. 4. With cooling the resting chloride efflux decreased with a Q10 of 1-3 and the resting chloride influx decreased with a Q10 of 2-8. This latter value, together with anomalous flux ratios for resting chloride fluxes may indicate an active uptake of chloride ions into the axon. 5. Cooling increased the extra efflux of potassium associated with nerve impulses with a Q10 of 1/1-5 and increased the extra influx of potassium with a Q10 of 1/3-3. 6. No extra efflux of chloride was detected at either temperature. Cooling produced no statistically significant change in the extra chloride influx but there was considerable scatter in the data. 7. Fluxes were computed as a function of temperature for standard action potentials with a variety of temperature coefficients for the conductances and rate constants. No single curve could match either the influx or the efflux data."} {"id": "PMID:182959", "title": "Effects of the ionophore X-537A on acetylcholine release at the frog neuromuscular junction.", "content": "1. X-537A is an ionophore that can carry cations across cell membranes. We studied its effects on spontaneous and stimulated quantal acetylcholine (ACh) release at the frog neuromuscular junction. 2. When neuromuscular transmission was blocked with high Mg2+ or with curare, X-537A markedly increased the end-plate potential (e.p.p.) amplitude. Then a few minutes later the e.p.p. disappeared. 3. When neuromuscular transmission was blocked with hypertonic saline solution, X-537A did not increase e.p.p. amplitude; it did produce many transmission failures. 4. X-537A decreased the depolarization of the end-plate produced by iontophoretically applied ACh. this may account in part for the disappearance of the e.p.p. in solutions containing the ionophore. 5. X-537A depolarized muscle fibres by about 15 mV. 6. When the extracellular divalent cation concentration was very low, X-537A had little or no effect on miniature end-plate potential (min.e.p.p.) frequency. 7. When a divalent cation was present in the extracellular fluid, X-537A increased the frequency of the min.e.p.p.s. The sequence of effectiveness of the divalent ions we have tested is: Ba2+ greater than Sr2+ greater than Ca2+ greater than Mn2+ congruent to Co2+ congruent to Ni2+ greater than Mg2+. There is a rough parallel between these results and the reported affinity of X-537A for various divalent ions. 8. The increase in min.e.p.p. frequency caused by X-537A was transitory, following the increase min.e.p.p. frequency fell to a very low rate or to zero. Then nerve stimulation did not cause quantal release. A second application of X-537A was without effect. 9. X-537A decreased min.e.p.p. amplitude, in accord with the effect on the sensitivity of the end-plate to ACh. 10. The results support the idea that increases in intracellular divalent cation concentrations trigger quantal release from nerve terminals and are involved in the disensitization of end plate receptors to ACh.", "contents": "Effects of the ionophore X-537A on acetylcholine release at the frog neuromuscular junction. 1. X-537A is an ionophore that can carry cations across cell membranes. We studied its effects on spontaneous and stimulated quantal acetylcholine (ACh) release at the frog neuromuscular junction. 2. When neuromuscular transmission was blocked with high Mg2+ or with curare, X-537A markedly increased the end-plate potential (e.p.p.) amplitude. Then a few minutes later the e.p.p. disappeared. 3. When neuromuscular transmission was blocked with hypertonic saline solution, X-537A did not increase e.p.p. amplitude; it did produce many transmission failures. 4. X-537A decreased the depolarization of the end-plate produced by iontophoretically applied ACh. this may account in part for the disappearance of the e.p.p. in solutions containing the ionophore. 5. X-537A depolarized muscle fibres by about 15 mV. 6. When the extracellular divalent cation concentration was very low, X-537A had little or no effect on miniature end-plate potential (min.e.p.p.) frequency. 7. When a divalent cation was present in the extracellular fluid, X-537A increased the frequency of the min.e.p.p.s. The sequence of effectiveness of the divalent ions we have tested is: Ba2+ greater than Sr2+ greater than Ca2+ greater than Mn2+ congruent to Co2+ congruent to Ni2+ greater than Mg2+. There is a rough parallel between these results and the reported affinity of X-537A for various divalent ions. 8. The increase in min.e.p.p. frequency caused by X-537A was transitory, following the increase min.e.p.p. frequency fell to a very low rate or to zero. Then nerve stimulation did not cause quantal release. A second application of X-537A was without effect. 9. X-537A decreased min.e.p.p. amplitude, in accord with the effect on the sensitivity of the end-plate to ACh. 10. The results support the idea that increases in intracellular divalent cation concentrations trigger quantal release from nerve terminals and are involved in the disensitization of end plate receptors to ACh."} {"id": "PMID:182961", "title": "The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the ability of sympathetic nerve stimulation to enhance growth and secretion in rat salivary glands in vivo.", "content": "1. The cyclic AMP content of the rat salivary glands was measured after sympathetic and parasympathetic nerve stimulation, and after the administration of isoprenaline and phenylephrine. 2. Stimulation of the sympathetic nerves (20 Hz, 1 msec supramaximal voltage for 30 sec of every min) initially raised the cyclic AMP level in both the parotid and submaxillary glands. The rise, which was blocked by propranolol, was not maintained and declined during stimulation from the maximum (reached after 3 min stimulation) to control levels after approximately 15 min. Stimulation of the parasympathetic nerves for 5 min did not raise the cyclic AMP levels. 3. Isoprenaline and phenylephrine raised the cyclic AMP level in both glands. 4. Theophylline enhanced the growth of the parotid and submaxillary glands as measured either by an increase in the wet and dry weights or in acinar axes lengths. N6O2-dibutyryl cyclic monophosphoric acid (dibutyryl cyclic AMP), did not enhance the growth of the glands. 5. It is concluded that cyclic AMP does not directly control cell growth in the rat salivary glands but may be a 'trigger' for events leading eventually to increased growth.", "contents": "The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the ability of sympathetic nerve stimulation to enhance growth and secretion in rat salivary glands in vivo. 1. The cyclic AMP content of the rat salivary glands was measured after sympathetic and parasympathetic nerve stimulation, and after the administration of isoprenaline and phenylephrine. 2. Stimulation of the sympathetic nerves (20 Hz, 1 msec supramaximal voltage for 30 sec of every min) initially raised the cyclic AMP level in both the parotid and submaxillary glands. The rise, which was blocked by propranolol, was not maintained and declined during stimulation from the maximum (reached after 3 min stimulation) to control levels after approximately 15 min. Stimulation of the parasympathetic nerves for 5 min did not raise the cyclic AMP levels. 3. Isoprenaline and phenylephrine raised the cyclic AMP level in both glands. 4. Theophylline enhanced the growth of the parotid and submaxillary glands as measured either by an increase in the wet and dry weights or in acinar axes lengths. N6O2-dibutyryl cyclic monophosphoric acid (dibutyryl cyclic AMP), did not enhance the growth of the glands. 5. It is concluded that cyclic AMP does not directly control cell growth in the rat salivary glands but may be a 'trigger' for events leading eventually to increased growth."} {"id": "PMID:182964", "title": "Synaptic depression related to presynaptic axon conduction block.", "content": "1. The depression of synaptic transmission, which occurs during prolonged repetitive activation, was examined in the opener muscle of the crayfish walking leg. 2. Excitatory post-synaptic potentials (e.p.s.p.s) initially facilitated but then declined to low amplitudes after about 4000 stimulus pulses had been delivered; this depression is presynaptic in origin; 3. Axon conduction blocks occured at points of bifurcation along the entire length of the presynaptic nerve. This resulted in failure of the nerve impulse to invade some branches of the terminal arborization. 4. Nerve terminal invasion failure caused either intermittent or complete inactiviation of some synaptic release sites; this was associated with depression of the post-synaptic response. 5. The statistics of transmitter release during prolonged repetitive stimulation were examined by focal extracellular recording methods. Transmitter release could be described by binomial statistics, and depression involved a drop in m, n and p. 6. The rate of spontaneous quantal release did not decrease, however, arguing against transmitter depletion. 7. It is concluded that repetitive stimulation eventually leads to depolarization of the axon membrane. This causes impulse propagation failure which reduces the number of synaptic release sites that are activated and mimics a drop in the effective stimulation rate; both effects cause synaptic depression.", "contents": "Synaptic depression related to presynaptic axon conduction block. 1. The depression of synaptic transmission, which occurs during prolonged repetitive activation, was examined in the opener muscle of the crayfish walking leg. 2. Excitatory post-synaptic potentials (e.p.s.p.s) initially facilitated but then declined to low amplitudes after about 4000 stimulus pulses had been delivered; this depression is presynaptic in origin; 3. Axon conduction blocks occured at points of bifurcation along the entire length of the presynaptic nerve. This resulted in failure of the nerve impulse to invade some branches of the terminal arborization. 4. Nerve terminal invasion failure caused either intermittent or complete inactiviation of some synaptic release sites; this was associated with depression of the post-synaptic response. 5. The statistics of transmitter release during prolonged repetitive stimulation were examined by focal extracellular recording methods. Transmitter release could be described by binomial statistics, and depression involved a drop in m, n and p. 6. The rate of spontaneous quantal release did not decrease, however, arguing against transmitter depletion. 7. It is concluded that repetitive stimulation eventually leads to depolarization of the axon membrane. This causes impulse propagation failure which reduces the number of synaptic release sites that are activated and mimics a drop in the effective stimulation rate; both effects cause synaptic depression."} {"id": "PMID:182965", "title": "Adverse effects of tris hydrochloride, a commonly used buffer in physiological media.", "content": "1. Tris 10mM, produced inhibition of motor responses to adrenergic motor nerve stimulation in all smooth muscles studied (rat anococcygeus and vas deferens perfused rabbit ear artery). Up to 30 mM Tris was without significant effect on those motor responses to cholinergic nerve stimulation examined (guinea-pig ileum). 2. a similar reduction in responses to endogenous motor agonists was seen only in the anococcygeus, while in the rabbit ear artery, responses to noradrenaline (NA) were potentiated. 3. tris consistently produced increased tone in the rat anococcygeus and rabbit aorta, but in no other tissue, Small reductions in tone were seen with Tris in spiral strips of rabbit ear artery. 4. inhibitory responses to adrenergic nerve stimulation and to NA in the rabbit jejunum and to inhibitory nerve stimulation in the rat anococcygeus were unaffected by Tris. 5. in the perfused rabbit heart Tris produced a negative inotropic effect and reduced responses to vagal stimulation. Responses to sympathetic nerve stimulation and to ACh and NA were not significantly altered. 6. up to 40 mM Tris had little effect on responses of the rat diaphragm to motor nerve stimulation. 7. the effects of Tris on the rat anococcygeus were not reduced by increased calcium levels but were reduced at lower incubation temperatures. The negative inotropic effect of Tris on the rabbit heart was also reduced at lower temperatures. 8. the buffer HEPES produced a reduction in responses to stimulation in the rat anococcygeus and vas deferens along, but at higher concentrations than those of Tris. Increases in tone in the anococcygeus and aorta were never seen with HEPES. 9. These results indicate that Tris in concentrations commonly used as a buffer in physiological salines can exert toxic effects on neuro-muscular transmission in smooth and cardiac muscle though not in skeletal muscle. The effects are variable, mainly presynaptic and appear to affect in particular motor and especially adrenergic transmission. They may be associated with intracellular metabolic actions of Tris.", "contents": "Adverse effects of tris hydrochloride, a commonly used buffer in physiological media. 1. Tris 10mM, produced inhibition of motor responses to adrenergic motor nerve stimulation in all smooth muscles studied (rat anococcygeus and vas deferens perfused rabbit ear artery). Up to 30 mM Tris was without significant effect on those motor responses to cholinergic nerve stimulation examined (guinea-pig ileum). 2. a similar reduction in responses to endogenous motor agonists was seen only in the anococcygeus, while in the rabbit ear artery, responses to noradrenaline (NA) were potentiated. 3. tris consistently produced increased tone in the rat anococcygeus and rabbit aorta, but in no other tissue, Small reductions in tone were seen with Tris in spiral strips of rabbit ear artery. 4. inhibitory responses to adrenergic nerve stimulation and to NA in the rabbit jejunum and to inhibitory nerve stimulation in the rat anococcygeus were unaffected by Tris. 5. in the perfused rabbit heart Tris produced a negative inotropic effect and reduced responses to vagal stimulation. Responses to sympathetic nerve stimulation and to ACh and NA were not significantly altered. 6. up to 40 mM Tris had little effect on responses of the rat diaphragm to motor nerve stimulation. 7. the effects of Tris on the rat anococcygeus were not reduced by increased calcium levels but were reduced at lower incubation temperatures. The negative inotropic effect of Tris on the rabbit heart was also reduced at lower temperatures. 8. the buffer HEPES produced a reduction in responses to stimulation in the rat anococcygeus and vas deferens along, but at higher concentrations than those of Tris. Increases in tone in the anococcygeus and aorta were never seen with HEPES. 9. These results indicate that Tris in concentrations commonly used as a buffer in physiological salines can exert toxic effects on neuro-muscular transmission in smooth and cardiac muscle though not in skeletal muscle. The effects are variable, mainly presynaptic and appear to affect in particular motor and especially adrenergic transmission. They may be associated with intracellular metabolic actions of Tris."} {"id": "PMID:182966", "title": "Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone.", "content": "1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter.", "contents": "Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone. 1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter."} {"id": "PMID:182967", "title": "Statistical fluctuations in charge transfer at Ia synapses on spinal motoneurones.", "content": "1. Net inward charge is calculated for unitary Ia e.p.s.p.s. evoked in spinal motoneurones. Fluctuations in this charge are used to describe the fluctuations in transmission at the Ia synapse. 2. The statistical details of variation in transmission at Ia synapses are largely obscured by noise, arising from spontaneous activity and recording apparatus. 3. A computational procedure is described, which utilized the measured statistical properties of the recording noise, and the measured charge histogram of the evoked e.p.s.p. (with noise) to calculate the variations in charge due to the e.p.s.p. alone. 4. The fluctuation in charge transmission at Ia synapses are, in general, non-quantal. Nor are they described by binomial or Poisson statistics. 5. It is suggested that the basic mode of transmission at a single terminal is all-or-none. The fluctuations result from the combined effect of failures at several terminals arising from a single afferent fibre. This hypothesis is supported by further analysis of these results in a subsequent paper (Edwards, Redman & Walmysley, 1976a).", "contents": "Statistical fluctuations in charge transfer at Ia synapses on spinal motoneurones. 1. Net inward charge is calculated for unitary Ia e.p.s.p.s. evoked in spinal motoneurones. Fluctuations in this charge are used to describe the fluctuations in transmission at the Ia synapse. 2. The statistical details of variation in transmission at Ia synapses are largely obscured by noise, arising from spontaneous activity and recording apparatus. 3. A computational procedure is described, which utilized the measured statistical properties of the recording noise, and the measured charge histogram of the evoked e.p.s.p. (with noise) to calculate the variations in charge due to the e.p.s.p. alone. 4. The fluctuation in charge transmission at Ia synapses are, in general, non-quantal. Nor are they described by binomial or Poisson statistics. 5. It is suggested that the basic mode of transmission at a single terminal is all-or-none. The fluctuations result from the combined effect of failures at several terminals arising from a single afferent fibre. This hypothesis is supported by further analysis of these results in a subsequent paper (Edwards, Redman & Walmysley, 1976a)."} {"id": "PMID:182968", "title": "Non-quantal fluctuations and transmission failures in charge transfer at Ia synapses on spinal motoneurones.", "content": "1. The origins of fluctuations in charge transfer during the generation of Ia e.p.s.p.s have been investigated. The discrete components which make up the fluctuating e.p.s.p. have been separated. 2. Some e.p.s.p.s fluctuate between two different amplitudes and time courses. These fluctuations have been analysed to show that charge transmission always occurs at one synaptic location, but not always at a second synaptic location. 3. The failures in transmission were study by stimulating the afferent fibre at different frequencies. Although different probabilities of failure were obtained at different frequencies, there was no systematic change in probability with increasing frequency. 4. Single afferents were tetanized and histograms of charge transfer computed during post-tetanic potentiation (p.t.p.). Only half of the units studied showed any p.t.p. In those that did, evidence was found for a decrease in the probability of failure during potentiation. 5. The results could not be used to distinguish between failure of the impulse to always propagate into the terminals, and failure of the terminals to release transmitter following adequate depolarization. 6. The fluctuations in transmission at a single synapse can be described by a binomial process with n = 1 and p less than or equal to 1. Junctional mechanisms consistent with this description are discussed. Alternative mechanisms which associate failures with failure of impulse transmission at afferent fibre branch points are also suggested.", "contents": "Non-quantal fluctuations and transmission failures in charge transfer at Ia synapses on spinal motoneurones. 1. The origins of fluctuations in charge transfer during the generation of Ia e.p.s.p.s have been investigated. The discrete components which make up the fluctuating e.p.s.p. have been separated. 2. Some e.p.s.p.s fluctuate between two different amplitudes and time courses. These fluctuations have been analysed to show that charge transmission always occurs at one synaptic location, but not always at a second synaptic location. 3. The failures in transmission were study by stimulating the afferent fibre at different frequencies. Although different probabilities of failure were obtained at different frequencies, there was no systematic change in probability with increasing frequency. 4. Single afferents were tetanized and histograms of charge transfer computed during post-tetanic potentiation (p.t.p.). Only half of the units studied showed any p.t.p. In those that did, evidence was found for a decrease in the probability of failure during potentiation. 5. The results could not be used to distinguish between failure of the impulse to always propagate into the terminals, and failure of the terminals to release transmitter following adequate depolarization. 6. The fluctuations in transmission at a single synapse can be described by a binomial process with n = 1 and p less than or equal to 1. Junctional mechanisms consistent with this description are discussed. Alternative mechanisms which associate failures with failure of impulse transmission at afferent fibre branch points are also suggested."} {"id": "PMID:182969", "title": "The effect of polarizing currents on unitary Ia excitatory post-synaptic potentials evoked in spinal motoneurones.", "content": "1. Depolarizing and hyperpolarizing currents were applied to motoneurones in which unitary Ia e.p.s.p.s were evoked. The results concentrate on those e.p.s.p.s which had time courses which were compatible with somatically located synapses. 2. No reversal of these e.p.s.p.s was observed. Depolarizing currents up to 150 nA simply reduced the peak amplitude. 3. Hyperpolarizing currents caused little, if any, increase in the peak amplitude of the e.p.s.p. The time course of decay became briefer as the membrane was hyperpolarized. 4. Changes in decay time course of the e.p.s.p. which accompanied depolarization and hyperpolarization could be attributed to changes in membrane conductances, rather than to changes in synaptic current time course. 5. The failure of the e.p.s.p. to increase with hyperpolarization was shown to be due to the failure of the synaptic current to increase, rather than to the shunting of anomalous rectification. 6. Chemical and electrical transmission are evaluated against these results and those of the preceding papers.", "contents": "The effect of polarizing currents on unitary Ia excitatory post-synaptic potentials evoked in spinal motoneurones. 1. Depolarizing and hyperpolarizing currents were applied to motoneurones in which unitary Ia e.p.s.p.s were evoked. The results concentrate on those e.p.s.p.s which had time courses which were compatible with somatically located synapses. 2. No reversal of these e.p.s.p.s was observed. Depolarizing currents up to 150 nA simply reduced the peak amplitude. 3. Hyperpolarizing currents caused little, if any, increase in the peak amplitude of the e.p.s.p. The time course of decay became briefer as the membrane was hyperpolarized. 4. Changes in decay time course of the e.p.s.p. which accompanied depolarization and hyperpolarization could be attributed to changes in membrane conductances, rather than to changes in synaptic current time course. 5. The failure of the e.p.s.p. to increase with hyperpolarization was shown to be due to the failure of the synaptic current to increase, rather than to the shunting of anomalous rectification. 6. Chemical and electrical transmission are evaluated against these results and those of the preceding papers."} {"id": "PMID:182970", "title": "Blood pressure and sleep in the rat in normotension and in neurogenic hypertension.", "content": "1. Blood pressure was recorded in normotensive rats (114 +/- 2 mmHg) and in those made hypertensive by baroreceptor denervation (135 +/- 4 mmHg) during natural sleep. The different states of the wakefulness-sleep cycle were identified by analysis of the frontal electrocorticogram, the cervical electromyogram and by behavioural changes. 2. During synchronized sleep the arterial pressure in the control animals usually remained unchanged as compared to values prevailing when the rats were awake and quiet. The blood pressure usually attained higher levels in the sino-aortically denervated rats during this state. 3. Coincidently with the short episodes of electrocortical desynchronization of the synchronized sleep the blood pressure exhibited rapid oscillations. These fluctuations were greater in the rats with neurogenic hypertension where there were large pressure drops. 4. During desynchronized (REM) sleep arterial pressure underwent marked oscillations. While in the control rats the pressure usually rose, the baroreceptor-denervated rats showed a severe reduction in pressure. Arterial pressure in denervated animals became lower than that of the control rats, 106 +/- 2 and 121 +/- 2 mmHg, respectively. 5. We interpret these results to mean that in the rat alterations in the sensitivity of the baroreceptor reflex could be an important factor in preventing the arterial pressure from rising to hypertensive levels during syndhronized sleep and from dropping to low values during desynchronized (REM) sleep.", "contents": "Blood pressure and sleep in the rat in normotension and in neurogenic hypertension. 1. Blood pressure was recorded in normotensive rats (114 +/- 2 mmHg) and in those made hypertensive by baroreceptor denervation (135 +/- 4 mmHg) during natural sleep. The different states of the wakefulness-sleep cycle were identified by analysis of the frontal electrocorticogram, the cervical electromyogram and by behavioural changes. 2. During synchronized sleep the arterial pressure in the control animals usually remained unchanged as compared to values prevailing when the rats were awake and quiet. The blood pressure usually attained higher levels in the sino-aortically denervated rats during this state. 3. Coincidently with the short episodes of electrocortical desynchronization of the synchronized sleep the blood pressure exhibited rapid oscillations. These fluctuations were greater in the rats with neurogenic hypertension where there were large pressure drops. 4. During desynchronized (REM) sleep arterial pressure underwent marked oscillations. While in the control rats the pressure usually rose, the baroreceptor-denervated rats showed a severe reduction in pressure. Arterial pressure in denervated animals became lower than that of the control rats, 106 +/- 2 and 121 +/- 2 mmHg, respectively. 5. We interpret these results to mean that in the rat alterations in the sensitivity of the baroreceptor reflex could be an important factor in preventing the arterial pressure from rising to hypertensive levels during syndhronized sleep and from dropping to low values during desynchronized (REM) sleep."} {"id": "PMID:182971", "title": "[The ACTH of the pituitary pars intermedia].", "content": "The present investigation suggests that the intermediate lobe contains corticotrophic cells that are morphologically similar to those of the adenohypophysis. It can also be concluded that the ACTH molecules extracted from the intermediate lobe do not differ from those from the adenohypophysis. The immunocytochemical studies confirm the presence of ACTH in the intermediate lobes of all species studied so far, and stimulate the question of the mechanism of ACTH synthesis at this level. The interrelationships between different peptides of the intermediate lobe, including LPH, ACTH, CLIP and MSH, require further investigations. The intermediate lobe synthesizes and releases ACTH in vitro. This release can be stimulated by crude extracts of the median eminence or of cerebral cortex, and does not seem to be controlled by the CRF. Although ACTH of the intermediate lobe intervenes in vivo in the response to a neurogenic stress, one may not assume that the intermediate lobe alone plays an important role in the maintenance of the adrenal cortex, as the adrenals are similarly affected by hypophysectomy or pars distalis removal.", "contents": "[The ACTH of the pituitary pars intermedia]. The present investigation suggests that the intermediate lobe contains corticotrophic cells that are morphologically similar to those of the adenohypophysis. It can also be concluded that the ACTH molecules extracted from the intermediate lobe do not differ from those from the adenohypophysis. The immunocytochemical studies confirm the presence of ACTH in the intermediate lobes of all species studied so far, and stimulate the question of the mechanism of ACTH synthesis at this level. The interrelationships between different peptides of the intermediate lobe, including LPH, ACTH, CLIP and MSH, require further investigations. The intermediate lobe synthesizes and releases ACTH in vitro. This release can be stimulated by crude extracts of the median eminence or of cerebral cortex, and does not seem to be controlled by the CRF. Although ACTH of the intermediate lobe intervenes in vivo in the response to a neurogenic stress, one may not assume that the intermediate lobe alone plays an important role in the maintenance of the adrenal cortex, as the adrenals are similarly affected by hypophysectomy or pars distalis removal."} {"id": "PMID:182972", "title": "[Hormonal control of the adenyl cyclase activity of adipose cell membranes prepared from badger, rabbit, fox and rat adipose tissues].", "content": "1. We have shown differences in hormonal regulation of adenylate cyclase activity in fat cell ghosts prepared from rat, rabbit, fox and badger adipose tissue, under the influence of catecholamines, ACTH and insulin. a) In the rat, catecholamines induced a large stimulation (+315%) of adenylate cyclase. b) In the rabbit, ACTH was the most effective hormone. c) In the fox and the badger, only catecholamines could stimulate adenylate cyclase. d) In both rat and rabbit, insulin did not reduce spontaneous enzymatic activity. Moreover, the activation of adenylate cyclase by ACTH in the rabbit was not altered by insulin, while in the rat, this hormone slightly decreased epinephrine stimulation. 2. Hormonal regulation of adenylate cyclase correlated with the lipolytic response.", "contents": "[Hormonal control of the adenyl cyclase activity of adipose cell membranes prepared from badger, rabbit, fox and rat adipose tissues]. 1. We have shown differences in hormonal regulation of adenylate cyclase activity in fat cell ghosts prepared from rat, rabbit, fox and badger adipose tissue, under the influence of catecholamines, ACTH and insulin. a) In the rat, catecholamines induced a large stimulation (+315%) of adenylate cyclase. b) In the rabbit, ACTH was the most effective hormone. c) In the fox and the badger, only catecholamines could stimulate adenylate cyclase. d) In both rat and rabbit, insulin did not reduce spontaneous enzymatic activity. Moreover, the activation of adenylate cyclase by ACTH in the rabbit was not altered by insulin, while in the rat, this hormone slightly decreased epinephrine stimulation. 2. Hormonal regulation of adenylate cyclase correlated with the lipolytic response."} {"id": "PMID:182975", "title": "[Neuromechanisms of reciprocal interrelation between jaw-opening and jaw-closing muscles in the cat (author's transl)].", "content": "Neural controlling mechanisms between the digastric (jaw-opening) and masseter (jaw-closing) muscles were studied in the cat. High threshold afferent impulses from the anterior belly of the digastric muscle to masseteric montoneurons in the trigeminal motor nucleus induced an EPSP-IPSP sequence of potentials with long latency, and high threshold afferent impulses from the masseter muscle also exerted a similar effect on digastric motoneurons in the same nucleus innervating the anterior belly of the digastric muscle. These results suggest that reciprocal inhibition via Ia interneurons as observed between the flexor and extensor muscles in the spinal cord does not exist between the digastric and masseter muscles in the cat. However, the respective motoneurons innervating the masseter and digastric muscles receive inputs of early excitation-late inhibition via high threshold afferent nerve fibers from each antagonistic muscle. As such, since EPSPs preceding IPSPs are recognized, these high threshold afferent impulses may exert not only a reciprocal inhibitory effect, but also a synchronous excitatory or inhibitory effect on the antagonistic motoneurons.", "contents": "[Neuromechanisms of reciprocal interrelation between jaw-opening and jaw-closing muscles in the cat (author's transl)]. Neural controlling mechanisms between the digastric (jaw-opening) and masseter (jaw-closing) muscles were studied in the cat. High threshold afferent impulses from the anterior belly of the digastric muscle to masseteric montoneurons in the trigeminal motor nucleus induced an EPSP-IPSP sequence of potentials with long latency, and high threshold afferent impulses from the masseter muscle also exerted a similar effect on digastric motoneurons in the same nucleus innervating the anterior belly of the digastric muscle. These results suggest that reciprocal inhibition via Ia interneurons as observed between the flexor and extensor muscles in the spinal cord does not exist between the digastric and masseter muscles in the cat. However, the respective motoneurons innervating the masseter and digastric muscles receive inputs of early excitation-late inhibition via high threshold afferent nerve fibers from each antagonistic muscle. As such, since EPSPs preceding IPSPs are recognized, these high threshold afferent impulses may exert not only a reciprocal inhibitory effect, but also a synchronous excitatory or inhibitory effect on the antagonistic motoneurons."} {"id": "PMID:182999", "title": "Non functional malignant nesidioblastoma. About one case (author's transl).", "content": "The authors report a case of, non functional, malignant, delta-cell, nesidioblastoma and, this way, make a review of the literature. It was a cephalic tumor, which manifestations were jaundice and loss weight and which hypervascular character involved an abdominal bruit. The angiographic aspect settle them to established correlation between functional and non functional tumors: the formers characteristic \"blush\", agreeding in fact with the initial phase of the growth, increase in a monstruous \"pseudoangiomatous\" aspect in the laters.", "contents": "Non functional malignant nesidioblastoma. About one case (author's transl). The authors report a case of, non functional, malignant, delta-cell, nesidioblastoma and, this way, make a review of the literature. It was a cephalic tumor, which manifestations were jaundice and loss weight and which hypervascular character involved an abdominal bruit. The angiographic aspect settle them to established correlation between functional and non functional tumors: the formers characteristic \"blush\", agreeding in fact with the initial phase of the growth, increase in a monstruous \"pseudoangiomatous\" aspect in the laters."} {"id": "PMID:183005", "title": "Induction of DNA polymerase in polyoma virus-infected mouse cells requires transcription and translation.", "content": "The induction of DNA polymerase activity and of DNA synthesis in polyoma virus-infected mouse kidney cells is inhibited by actinomycin D and cycloheximide, even in cells that are already T-antigen positive. This indicates that the induction of the DNA-synthesizing apparatus requires transcription and translation. The increase in cellular DNA polymerase activity and in the DNA synthesizing capacity follows the appearance of T-antigen only after a characteristic lag period of several hours.", "contents": "Induction of DNA polymerase in polyoma virus-infected mouse cells requires transcription and translation. The induction of DNA polymerase activity and of DNA synthesis in polyoma virus-infected mouse kidney cells is inhibited by actinomycin D and cycloheximide, even in cells that are already T-antigen positive. This indicates that the induction of the DNA-synthesizing apparatus requires transcription and translation. The increase in cellular DNA polymerase activity and in the DNA synthesizing capacity follows the appearance of T-antigen only after a characteristic lag period of several hours."} {"id": "PMID:183006", "title": "Avian leukosis viruses of different subgroups and types isolated after passage of Rous sarcoma virus-Rous-associated virus-0 in cells from different ring-necked pheasant embryos.", "content": "Avian leukosis viruses of subgroups A and F (RAV-A and RAV-F) arose at a low rate after passage of Rous sarcoma virus-Rous-associated virus-0, which is subgroup E, in cells from ring-necked pheasant embryos. In cells of two embryos, all of the viruses isolated after virus passage were RAV-F. However, in cells of a third embryo, both RAV-A and RAV-F were isolated. In addition, there sometimes were type-specific differences among the different isolates of RAV-A and RAV-F from the cells of single embryos. These results indicate that the RAV-A and RAV-F probably arose by recombination of viral and cellular genes, that different ring-necked pheasant embryo may have different endogenous avian leukosis virus-related nucleotide sequences, and that recombination at different sites in these endogenous sequences might give rise to type-specific differences among the RAV-A and RAV-F.", "contents": "Avian leukosis viruses of different subgroups and types isolated after passage of Rous sarcoma virus-Rous-associated virus-0 in cells from different ring-necked pheasant embryos. Avian leukosis viruses of subgroups A and F (RAV-A and RAV-F) arose at a low rate after passage of Rous sarcoma virus-Rous-associated virus-0, which is subgroup E, in cells from ring-necked pheasant embryos. In cells of two embryos, all of the viruses isolated after virus passage were RAV-F. However, in cells of a third embryo, both RAV-A and RAV-F were isolated. In addition, there sometimes were type-specific differences among the different isolates of RAV-A and RAV-F from the cells of single embryos. These results indicate that the RAV-A and RAV-F probably arose by recombination of viral and cellular genes, that different ring-necked pheasant embryo may have different endogenous avian leukosis virus-related nucleotide sequences, and that recombination at different sites in these endogenous sequences might give rise to type-specific differences among the RAV-A and RAV-F."} {"id": "PMID:183007", "title": "Action of ethyl and methyl methane sulfonates on DNA injection and genetic recombination in T7 bacteriophage.", "content": "After treatment with methyl or ethyl methane sulfonate, T7 amber mutants display a reduced capacity for recombination. Moreover, alkylation reduces recombination frequency involving markers on the right-hand side of the genetic map more than it reduces recombination frequency involving markers on the left-hand side. We interpret this to mean that alkylation can stop DNA injection at any point along the DNA molecule, and that T7 phage injects its DNA in a unique fashion starting from the end carrying the genes for early proteins.", "contents": "Action of ethyl and methyl methane sulfonates on DNA injection and genetic recombination in T7 bacteriophage. After treatment with methyl or ethyl methane sulfonate, T7 amber mutants display a reduced capacity for recombination. Moreover, alkylation reduces recombination frequency involving markers on the right-hand side of the genetic map more than it reduces recombination frequency involving markers on the left-hand side. We interpret this to mean that alkylation can stop DNA injection at any point along the DNA molecule, and that T7 phage injects its DNA in a unique fashion starting from the end carrying the genes for early proteins."} {"id": "PMID:183008", "title": "Encephalomyocarditis virus RNA: variations in polyadenylic acid content and biological activity.", "content": "Encephalomyocarditis (EMC) viral RNA was isolated from purified virus grown in Ehrlich ascites tumor cells. The viral RNA was found to contain polyadenylic acid [poly(A)] regions that were very heterogeneous in length. Chromatography of the EMC viral RNA on oligo(dT)-cellulose columns separated the RNA into three distinct fractions (peaks 1 to 3). Approximately 20% of the EMC viral RNA appeared as peak 1, 40% as peak 2, and 40% as peak 3. The RNA in each fraction appeared to be intact as shown by co-sedimentation with 35S unfractionated EMC viral RNA in SDS-sucrose density gradients. Approximately 95 to 100% of peaks 1 and 3, and 60 to 70% of peak 2, reappeared at the same elution position after rechromatography on oligo(dT)-cellulose. The RNA in peak 1 contained poly(A) with an average length of 16 nucleotides, peak 2 contained poly(A) with an average of 26 nucleotides, and peak 3 contained an average of 74 nucleotides in its poly(A) region. The distribution in the three fractions, as well as the average length of the poly(A) moieties, was relatively unaffected by changes in the cell suspension medium used during infection. Finally, each of the three viral RNA fractions was assayed for biological activity using an infectious RNA assay on L-cell monolayers. Infectivity of the viral RNA was found to increase with poly(A) length, with peak 3 viral RNA being approximately 10 times more infectious than peak 1 viral RNA.", "contents": "Encephalomyocarditis virus RNA: variations in polyadenylic acid content and biological activity. Encephalomyocarditis (EMC) viral RNA was isolated from purified virus grown in Ehrlich ascites tumor cells. The viral RNA was found to contain polyadenylic acid [poly(A)] regions that were very heterogeneous in length. Chromatography of the EMC viral RNA on oligo(dT)-cellulose columns separated the RNA into three distinct fractions (peaks 1 to 3). Approximately 20% of the EMC viral RNA appeared as peak 1, 40% as peak 2, and 40% as peak 3. The RNA in each fraction appeared to be intact as shown by co-sedimentation with 35S unfractionated EMC viral RNA in SDS-sucrose density gradients. Approximately 95 to 100% of peaks 1 and 3, and 60 to 70% of peak 2, reappeared at the same elution position after rechromatography on oligo(dT)-cellulose. The RNA in peak 1 contained poly(A) with an average length of 16 nucleotides, peak 2 contained poly(A) with an average of 26 nucleotides, and peak 3 contained an average of 74 nucleotides in its poly(A) region. The distribution in the three fractions, as well as the average length of the poly(A) moieties, was relatively unaffected by changes in the cell suspension medium used during infection. Finally, each of the three viral RNA fractions was assayed for biological activity using an infectious RNA assay on L-cell monolayers. Infectivity of the viral RNA was found to increase with poly(A) length, with peak 3 viral RNA being approximately 10 times more infectious than peak 1 viral RNA."} {"id": "PMID:183009", "title": "Size of murine RNA tumor virus-specific nuclear RNA molecules.", "content": "About 1% of the total RNA of cell lines producing murine leukemia virus is virus-specific RNA. About one-third of the virus-specific RNA is located within the nucleus. The size distribution of virus-specific RNA was determined before and after denaturation. Before denaturation, virus-specific RNA sequences sedimented as a heterogeneous population of RNA molecules, some of which sedimented very rapidly. After denaturation, most of the virus-specific RNA had a sedimentation coefficient of 35S or lower, but a small fraction of the nuclear virus-specific RNA sedimented more rapidly than 35S RNA even after denaturation.", "contents": "Size of murine RNA tumor virus-specific nuclear RNA molecules. About 1% of the total RNA of cell lines producing murine leukemia virus is virus-specific RNA. About one-third of the virus-specific RNA is located within the nucleus. The size distribution of virus-specific RNA was determined before and after denaturation. Before denaturation, virus-specific RNA sequences sedimented as a heterogeneous population of RNA molecules, some of which sedimented very rapidly. After denaturation, most of the virus-specific RNA had a sedimentation coefficient of 35S or lower, but a small fraction of the nuclear virus-specific RNA sedimented more rapidly than 35S RNA even after denaturation."} {"id": "PMID:183010", "title": "Isolation and characterization of a heat-inducible simian virus 40 mutant.", "content": "We have isolated a new type of temperature-sensitive mutant of simian virus 40 (SV40) that is capable of productive infection in permissive cells but not of maintenance of viral DNA integration in transformed cells at the conditional temperature. Virus development is induced when cells transformed by this mutant are shifted to temperatures above 39 degrees C, but is not induced below this temperature. The plaque-purified, temperature-sensitive mutant virus confers heat inducibility to new host cells, indicating that the conditional function is a property of the viral genome. Unlike previously described temperature-sensitive SV40 mutants, in (ts)-1501 is capable of productive infection in permissive cells at the conditional temperature. The morphology, growth, and oncogenicity of in (ts)-1501-transformed cells at 37 degrees C are similar to those of cell lines transformed by wild-type SV40. HK10-c2(in(ts)-1501), a cloned cell line, transformed at 37 degrees C by the mutant virus, exhibits a transient increase in DNA synthesis before cell death at the conditional temperature. Many properties of in(ts)-1501 are analogous to those of the heat-inducible mutants of bacteriophages in which a heat-inactivated protein is responsible for the stable integration of the prophage in the bacterial chromosome.", "contents": "Isolation and characterization of a heat-inducible simian virus 40 mutant. We have isolated a new type of temperature-sensitive mutant of simian virus 40 (SV40) that is capable of productive infection in permissive cells but not of maintenance of viral DNA integration in transformed cells at the conditional temperature. Virus development is induced when cells transformed by this mutant are shifted to temperatures above 39 degrees C, but is not induced below this temperature. The plaque-purified, temperature-sensitive mutant virus confers heat inducibility to new host cells, indicating that the conditional function is a property of the viral genome. Unlike previously described temperature-sensitive SV40 mutants, in (ts)-1501 is capable of productive infection in permissive cells at the conditional temperature. The morphology, growth, and oncogenicity of in (ts)-1501-transformed cells at 37 degrees C are similar to those of cell lines transformed by wild-type SV40. HK10-c2(in(ts)-1501), a cloned cell line, transformed at 37 degrees C by the mutant virus, exhibits a transient increase in DNA synthesis before cell death at the conditional temperature. Many properties of in(ts)-1501 are analogous to those of the heat-inducible mutants of bacteriophages in which a heat-inactivated protein is responsible for the stable integration of the prophage in the bacterial chromosome."} {"id": "PMID:183011", "title": "Association of the polioviral RNA polymerase complex with phospholipid membranes.", "content": "Polioviral RNA polymerase complex, which consists of enzyme, template, and nascent RNA, is membrane bound in vivo. The solubilized RNA polymerase complex associated spontaneously in vitro with phospholipid bilayer membranes (liposomes) of defined composition. The degree of association at 37 degrees C was greater for those membranes that were more fluid, suggesting that the binding involves the interaction of the RNA polymerase complex with the hydrocarbon chains in the interior of the lipid bilayer. The polymerase activity was not enhanced by addition of the lipid; in fact, the addition of some of the longer-chain lipids resulted in up to a 40% inhibition of the polymerase activity. Spin-label electron paramagnetic resonance experiments, which measured the membrane fluidity, and kinetic experiments on the rate of incorporation of tritiated UTP into RNA by the polymerase were performed as a function of temperature. The results indicated that the activity of the polymerase was not affected by the physical state of the phospholipid membrane and that its active site was not intimately associated with the membrane. Analysis of both the viral and host polypeptides associated with the smooth membrane-bound polymerase indicated that X was the primary viral polypeptide present. In addition, host polypeptides of molecular weight 86,000, 62,000, 54,000, and 46,000 were also present. If the membrane was disrupted with detergent, polypeptide X was released from the polymerase activity, suggesting that X may play a role in binding the polymerase to the membrane. In an analogous manner, polypeptide X associated spontaneously with phospholipid membranes to a greater extent than the capsid polypeptides. Analysis of both the host and viral polypeptides associated with the viral RNA polymerase purified by precipitation in 2 M LiCl indicated that host polypeptides of molecular weight 106,000, 38,000, 33,000, and 14,000 were the major constituents, whereas relatively small amounts of the viral polypeptides were present. It was confirmed that of the viral polypeptides found, polypeptide 4 was present in the largest amount.", "contents": "Association of the polioviral RNA polymerase complex with phospholipid membranes. Polioviral RNA polymerase complex, which consists of enzyme, template, and nascent RNA, is membrane bound in vivo. The solubilized RNA polymerase complex associated spontaneously in vitro with phospholipid bilayer membranes (liposomes) of defined composition. The degree of association at 37 degrees C was greater for those membranes that were more fluid, suggesting that the binding involves the interaction of the RNA polymerase complex with the hydrocarbon chains in the interior of the lipid bilayer. The polymerase activity was not enhanced by addition of the lipid; in fact, the addition of some of the longer-chain lipids resulted in up to a 40% inhibition of the polymerase activity. Spin-label electron paramagnetic resonance experiments, which measured the membrane fluidity, and kinetic experiments on the rate of incorporation of tritiated UTP into RNA by the polymerase were performed as a function of temperature. The results indicated that the activity of the polymerase was not affected by the physical state of the phospholipid membrane and that its active site was not intimately associated with the membrane. Analysis of both the viral and host polypeptides associated with the smooth membrane-bound polymerase indicated that X was the primary viral polypeptide present. In addition, host polypeptides of molecular weight 86,000, 62,000, 54,000, and 46,000 were also present. If the membrane was disrupted with detergent, polypeptide X was released from the polymerase activity, suggesting that X may play a role in binding the polymerase to the membrane. In an analogous manner, polypeptide X associated spontaneously with phospholipid membranes to a greater extent than the capsid polypeptides. Analysis of both the host and viral polypeptides associated with the viral RNA polymerase purified by precipitation in 2 M LiCl indicated that host polypeptides of molecular weight 106,000, 38,000, 33,000, and 14,000 were the major constituents, whereas relatively small amounts of the viral polypeptides were present. It was confirmed that of the viral polypeptides found, polypeptide 4 was present in the largest amount."} {"id": "PMID:183012", "title": "Analysis of in vitro transcription products of intracellular vesicular stomatitis virus RNA polymerase.", "content": "The intracellular transcriptase complex of vesicular stomatitis virus-infected L cells synthesized RNA complementary to the entire infectious virus genome at either 37 degrees C or 28 degrees C in vitro. Not all sequences were present at the same frequency, however; copies of that segment of the genome common to the LT defective particles were present at 20 to 100 times higher frequently than copies of the genome segment common to the ST defective particle. The less frequent region was transcribed somewhat more effectively at 28 degrees C than at 37 degrees C. The results suggest that transcriptional regulation rather than selective degradation is responsible for the differential accumulation of RNA.", "contents": "Analysis of in vitro transcription products of intracellular vesicular stomatitis virus RNA polymerase. The intracellular transcriptase complex of vesicular stomatitis virus-infected L cells synthesized RNA complementary to the entire infectious virus genome at either 37 degrees C or 28 degrees C in vitro. Not all sequences were present at the same frequency, however; copies of that segment of the genome common to the LT defective particles were present at 20 to 100 times higher frequently than copies of the genome segment common to the ST defective particle. The less frequent region was transcribed somewhat more effectively at 28 degrees C than at 37 degrees C. The results suggest that transcriptional regulation rather than selective degradation is responsible for the differential accumulation of RNA."} {"id": "PMID:183013", "title": "Nucleotide sequence that binds primer for DNA synthesis to the avian sarcoma virus genome.", "content": "Initiation of transcription from the genome of avian sarcoma virus by RNA-directed DNA polymerase in vitro requires tRNAtrp as a primer. The tRNA is bound to the viral genome by a sequence of 16 contiguous nucleotides (U-C-A-C-G-U-C-G-G-G-G-U-C-A-C-Cp), beginning with the penultimate base at the 3' terminus of the primer and extending through the acceptor stem into loop IV of the tRNA. Consequently, the native conformation of the tRNA must be disrupted by the binding of primer to the viral genome. The binding sequence does not include two adjacent residues of pseudouridine in loop IV, which distinguish the primer from many other tRNAs, and the 3' terminal adenosine of primer may also be excluded from base pairing with the viral genome.", "contents": "Nucleotide sequence that binds primer for DNA synthesis to the avian sarcoma virus genome. Initiation of transcription from the genome of avian sarcoma virus by RNA-directed DNA polymerase in vitro requires tRNAtrp as a primer. The tRNA is bound to the viral genome by a sequence of 16 contiguous nucleotides (U-C-A-C-G-U-C-G-G-G-G-U-C-A-C-Cp), beginning with the penultimate base at the 3' terminus of the primer and extending through the acceptor stem into loop IV of the tRNA. Consequently, the native conformation of the tRNA must be disrupted by the binding of primer to the viral genome. The binding sequence does not include two adjacent residues of pseudouridine in loop IV, which distinguish the primer from many other tRNAs, and the 3' terminal adenosine of primer may also be excluded from base pairing with the viral genome."} {"id": "PMID:183014", "title": "Conditional lethal mutants of adenovirus type 2-simian virus 40 hybrids. II. Ad2+ND1 host-range mutants that synthesize fragments of the Ad2+ND1 30K protein.", "content": "Adenovirus type 2 (Ad2) grows 1,000 times less well in monkey cells than in human cells. This defect can be overcome, not only upon co-infection of cells with simian virus 40 (SV40), but also when the relevant part of the SV40 genome is integrated into the adenovirus genome to form an adenovirus-SV40 hybrid virus. We have used the nondefective Ad2-SV40 hybrid virus Ad2+ND1, which contains an insertion of 17% of the SV40 genome, to isolate host-range mutants which are defective in growth on monkey cells although they grow normally on human cells. Like Ad2, these mutants are defective in the synthesis of late proteins in monkey cells. A 30,000-molecular-weight protein (30K), unique to Ad2+ND1-infected cells, can be synthesized in vitro, using Ad2+ND1 mRNA that contains SV40 sequences. 30K is not seen in cells infected with those host-range mutants that are most defective in growth on monkey cells, and translation in vitro of SV40-specific mRNA from these cells produces new unique polypeptides, instead of 30K. Genetic and biochemical analyses indicate that these mutants carry point mutations rather than deletions.", "contents": "Conditional lethal mutants of adenovirus type 2-simian virus 40 hybrids. II. Ad2+ND1 host-range mutants that synthesize fragments of the Ad2+ND1 30K protein. Adenovirus type 2 (Ad2) grows 1,000 times less well in monkey cells than in human cells. This defect can be overcome, not only upon co-infection of cells with simian virus 40 (SV40), but also when the relevant part of the SV40 genome is integrated into the adenovirus genome to form an adenovirus-SV40 hybrid virus. We have used the nondefective Ad2-SV40 hybrid virus Ad2+ND1, which contains an insertion of 17% of the SV40 genome, to isolate host-range mutants which are defective in growth on monkey cells although they grow normally on human cells. Like Ad2, these mutants are defective in the synthesis of late proteins in monkey cells. A 30,000-molecular-weight protein (30K), unique to Ad2+ND1-infected cells, can be synthesized in vitro, using Ad2+ND1 mRNA that contains SV40 sequences. 30K is not seen in cells infected with those host-range mutants that are most defective in growth on monkey cells, and translation in vitro of SV40-specific mRNA from these cells produces new unique polypeptides, instead of 30K. Genetic and biochemical analyses indicate that these mutants carry point mutations rather than deletions."} {"id": "PMID:183015", "title": "Translation of individual host mRNA's in MPC-11 cells is differentially suppressed after infection by vesicular stomatitis virus.", "content": "Infection of MPC-11 mouse plasmacytoma cells by vesicular stomatitis virus results in 30 to 35% reduction in [35S]methionine incorporation into total proteins within 30 min postinfection. By 6 h postinfection, total protein synthesis is reduced by 80 to 90%. However, even by 30 min postinfection, a differential suppression of the synthesis of individual host protein is observed. The synthesis of the immunoglobin G (IgG) heavy chain (H), and, in particular, the synthesis of IgG light chain (L), is considerably more resistant to vesicular stomatitis virus-induced inhibition than is the synthesis of the non-IgG proteins as a whole; e.g., when the synthesis of non-IgG proteins was reduced by 41%, the synthesis of the H and L chains was reduced by 28 and 7%, respectively. Furthermore, these alterations in the relative synthesis of the L chain, H chain, and non-IgG are comparable to the alterations previously observed in uninfected MPC-11 cells when the overall rate of polypeptide chain initiation was selectively reduced (D.L. Nuss and G. Koch, 1976). These results are discussed in terms of the strategy of virus-directed suppression of host mRNA translation.", "contents": "Translation of individual host mRNA's in MPC-11 cells is differentially suppressed after infection by vesicular stomatitis virus. Infection of MPC-11 mouse plasmacytoma cells by vesicular stomatitis virus results in 30 to 35% reduction in [35S]methionine incorporation into total proteins within 30 min postinfection. By 6 h postinfection, total protein synthesis is reduced by 80 to 90%. However, even by 30 min postinfection, a differential suppression of the synthesis of individual host protein is observed. The synthesis of the immunoglobin G (IgG) heavy chain (H), and, in particular, the synthesis of IgG light chain (L), is considerably more resistant to vesicular stomatitis virus-induced inhibition than is the synthesis of the non-IgG proteins as a whole; e.g., when the synthesis of non-IgG proteins was reduced by 41%, the synthesis of the H and L chains was reduced by 28 and 7%, respectively. Furthermore, these alterations in the relative synthesis of the L chain, H chain, and non-IgG are comparable to the alterations previously observed in uninfected MPC-11 cells when the overall rate of polypeptide chain initiation was selectively reduced (D.L. Nuss and G. Koch, 1976). These results are discussed in terms of the strategy of virus-directed suppression of host mRNA translation."} {"id": "PMID:183016", "title": "Human cytomegalovirus: glycoproteins associated with virions and dense bodies.", "content": "The glycoproteins associated with the membranes of cytomegalovirions and dense bodies were characterized by their relative mobility, percentage of glucosamine incorporation, and molecular weight. Eight glycopolypeptides were repeatedly detectable. Three glycopolypeptides of higher molecular weight with low levels of glucosamine incorporation were occasionally detectable. These latter glycopolypeptides may be precursors or aggregates of the glycopolypeptides with lower molecular weights. The glycoproteins associated with the membranes were on the surface, as determined by iodination with 125I of virions and dense bodies partially purified in gradients of D-sorbitol. Velocity centrifugation in linear gradients of D-sorbitol was used to obtain concentrated and partially purified preparations of infectious cytomegalovirus. Viral infectivity and the membranes of cytomegalovirions and dense bodies were stable in gradients of sorbitol, but cellular contaminants were not completely removed. Additional centrifugation in CsCl separated both cellular contaminants and viral nucleocapsids from virions and dense bodies. Many dense bodies, which are considered to be aberrant forms of cytomegalovirus, had the same size, sedimentation properties, and density as virions. Consequently, they were not separable from virions by various centrifugation techniques. Electron microscopy demonstrated that purified virions and dense bodies were qualitatively free of extraneous material and that each dense body was bounded by a membrane, as evidenced by its double-tract appearance. Antisera to a preparation of purified virions and dense bodies, or to their glycoproteins, contained antibodies that neutralized viral infectivity and reacted with antigens in cells infected with cytomegalovirus. However, these same antisera did not contain antibodies that reacted with uninfected cells. The glycoproteins associated with the membranes of cytomegalovirions and dense bodies are considered to be specified by the cytomegalovirus genome.", "contents": "Human cytomegalovirus: glycoproteins associated with virions and dense bodies. The glycoproteins associated with the membranes of cytomegalovirions and dense bodies were characterized by their relative mobility, percentage of glucosamine incorporation, and molecular weight. Eight glycopolypeptides were repeatedly detectable. Three glycopolypeptides of higher molecular weight with low levels of glucosamine incorporation were occasionally detectable. These latter glycopolypeptides may be precursors or aggregates of the glycopolypeptides with lower molecular weights. The glycoproteins associated with the membranes were on the surface, as determined by iodination with 125I of virions and dense bodies partially purified in gradients of D-sorbitol. Velocity centrifugation in linear gradients of D-sorbitol was used to obtain concentrated and partially purified preparations of infectious cytomegalovirus. Viral infectivity and the membranes of cytomegalovirions and dense bodies were stable in gradients of sorbitol, but cellular contaminants were not completely removed. Additional centrifugation in CsCl separated both cellular contaminants and viral nucleocapsids from virions and dense bodies. Many dense bodies, which are considered to be aberrant forms of cytomegalovirus, had the same size, sedimentation properties, and density as virions. Consequently, they were not separable from virions by various centrifugation techniques. Electron microscopy demonstrated that purified virions and dense bodies were qualitatively free of extraneous material and that each dense body was bounded by a membrane, as evidenced by its double-tract appearance. Antisera to a preparation of purified virions and dense bodies, or to their glycoproteins, contained antibodies that neutralized viral infectivity and reacted with antigens in cells infected with cytomegalovirus. However, these same antisera did not contain antibodies that reacted with uninfected cells. The glycoproteins associated with the membranes of cytomegalovirions and dense bodies are considered to be specified by the cytomegalovirus genome."} {"id": "PMID:183017", "title": "RNA polymerase activity in purified virions of avian reticuloendotheliosis viruses.", "content": "An RNA polymerase activity that synthesizes a U-rich RNA hydrogen bonded to a large viral RNA molecule was found in the cores of virions of avian reticuloendotheliosis viruses (REV). The RNA polymerase activity was separable from the DNA polymerase activity of REV virions. The 5'-terminus of the newly synthesized RNA was A. In addition, a tRNA nucleotidyl transferase activity, which added -CpCpA ends to tRNA, appears to be present in the REV virions.", "contents": "RNA polymerase activity in purified virions of avian reticuloendotheliosis viruses. An RNA polymerase activity that synthesizes a U-rich RNA hydrogen bonded to a large viral RNA molecule was found in the cores of virions of avian reticuloendotheliosis viruses (REV). The RNA polymerase activity was separable from the DNA polymerase activity of REV virions. The 5'-terminus of the newly synthesized RNA was A. In addition, a tRNA nucleotidyl transferase activity, which added -CpCpA ends to tRNA, appears to be present in the REV virions."} {"id": "PMID:183018", "title": "Early events in polyoma virus infection: attachment, penetration, and nuclear entry.", "content": "The plaque-assay technique was used as a tool to determine the optimal conditions for adsorption of polyoma virions to host cells. Using these optimal conditions of adsorption, an electron microscopy study of the early events of infection was performed. By electron microscopy and autoradiography, it was demonstrated that both the viral coat proteins and DNA arrive simultaneously in the nucleus as early as 15 min postinfection. When horseradish peroxidase-labeled virions, pseudovirions, and capsids were used to infect cells, only the particles with nucleic acid or a factor(s) associated with the nucleic acid, i.e., histones, appeared to enter the nucleus. Moreover, when virions were used to infect either permissive or nonpermissive cells, identical early events of viral infection, i.e., adsorption, penetration, and nuclear transport, were observed, suggesting that these early events of infection are a property of the virion and not the host cell.", "contents": "Early events in polyoma virus infection: attachment, penetration, and nuclear entry. The plaque-assay technique was used as a tool to determine the optimal conditions for adsorption of polyoma virions to host cells. Using these optimal conditions of adsorption, an electron microscopy study of the early events of infection was performed. By electron microscopy and autoradiography, it was demonstrated that both the viral coat proteins and DNA arrive simultaneously in the nucleus as early as 15 min postinfection. When horseradish peroxidase-labeled virions, pseudovirions, and capsids were used to infect cells, only the particles with nucleic acid or a factor(s) associated with the nucleic acid, i.e., histones, appeared to enter the nucleus. Moreover, when virions were used to infect either permissive or nonpermissive cells, identical early events of viral infection, i.e., adsorption, penetration, and nuclear transport, were observed, suggesting that these early events of infection are a property of the virion and not the host cell."} {"id": "PMID:183019", "title": "Comparison of JC and BK human papovaviruses with simian virus 40: DNA homology studies.", "content": "Studies were performed to ascertain the relationship of human papovavirus JC to BK virus and to simian virus 40 (SV40) by further restriction endonuclease analysis and by DNA-DNA competition hybridization on membrane filters. Form I DNA extracted from two new isolates from cases of progressive multifocal leukoencephalopathy of human papovaviruses that were JC-like in their antigenic properties were found to yield restriction endonuclease fragmentation patterns similar to those of prototypic JC virus DNA and different from those of BK or SV40. Form I DNA preparations of JC and BK viruses were found to be related to each other and to SV40 DNA to a similar extent, with JC and BK virus DNAs containing sequences homologous to both early and late regions of the SV40 genome. The relatedness in each comparison was less than 50%, and heterologous hybrids between either JC or BK and SV40 DNAs were found to be less stable than homologous SV40-SV40 hybrids in high concentrations of formamide, suggesting substantial mismatch within homologous regions, to the extent of 15 to 30%. The new JC-like isolates were also studied in competition hybridization reactions with SV40 DNA and yielded results similar to those obtained with JC virus.", "contents": "Comparison of JC and BK human papovaviruses with simian virus 40: DNA homology studies. Studies were performed to ascertain the relationship of human papovavirus JC to BK virus and to simian virus 40 (SV40) by further restriction endonuclease analysis and by DNA-DNA competition hybridization on membrane filters. Form I DNA extracted from two new isolates from cases of progressive multifocal leukoencephalopathy of human papovaviruses that were JC-like in their antigenic properties were found to yield restriction endonuclease fragmentation patterns similar to those of prototypic JC virus DNA and different from those of BK or SV40. Form I DNA preparations of JC and BK viruses were found to be related to each other and to SV40 DNA to a similar extent, with JC and BK virus DNAs containing sequences homologous to both early and late regions of the SV40 genome. The relatedness in each comparison was less than 50%, and heterologous hybrids between either JC or BK and SV40 DNAs were found to be less stable than homologous SV40-SV40 hybrids in high concentrations of formamide, suggesting substantial mismatch within homologous regions, to the extent of 15 to 30%. The new JC-like isolates were also studied in competition hybridization reactions with SV40 DNA and yielded results similar to those obtained with JC virus."} {"id": "PMID:183020", "title": "Differential response of type C and intracisternal type A particle markers in cells treated with iododeoxyuridine and dexamethasone.", "content": "Mouse neuroblastoma cells containing intracisternal type A particles were treated with iododeoxyuridine and dexamethasone to induce the release of type C oncornavirus particles. For 5 days after treatment, antigenic markers and DNA polymerase activities specific to particles of each of the two types were assayed in the cells and in pellets obtained by high-speed centrifugation of the culture fluid. There was a marked release of C-particle antigen (p30) and DNA polymerase activity in extracellular particulate form, reaching a maximum on day 3 after treatment and falling thereafter. In contrast, no extracellular A-particle antigen was detected, and A-particle-specific DNA polymerase activity in the medium pellets did not increase from the original very low level. Electron microscopy confirmed the presence of free type C virus particles, but not intracisternal type A particles, in the culture fluid. Although intracellular levels of C-particle antigen rose 20- to 30-fold per milligram of cell protein, intracellular A-particle antigen and DNA polymerase activity did not vary more than two-fold. The relative rate of A-particle synthesis in the treated cells, as judged by incorporation of radioactive amino acids into the major structural protein (P73), was also unchanged over the period of observation. Thus, the induction of type C virus particle formation in cultured neuroblastoma cells had no detectable effect on the quantity, synthesis rate, or location of intracisternal type A particles.", "contents": "Differential response of type C and intracisternal type A particle markers in cells treated with iododeoxyuridine and dexamethasone. Mouse neuroblastoma cells containing intracisternal type A particles were treated with iododeoxyuridine and dexamethasone to induce the release of type C oncornavirus particles. For 5 days after treatment, antigenic markers and DNA polymerase activities specific to particles of each of the two types were assayed in the cells and in pellets obtained by high-speed centrifugation of the culture fluid. There was a marked release of C-particle antigen (p30) and DNA polymerase activity in extracellular particulate form, reaching a maximum on day 3 after treatment and falling thereafter. In contrast, no extracellular A-particle antigen was detected, and A-particle-specific DNA polymerase activity in the medium pellets did not increase from the original very low level. Electron microscopy confirmed the presence of free type C virus particles, but not intracisternal type A particles, in the culture fluid. Although intracellular levels of C-particle antigen rose 20- to 30-fold per milligram of cell protein, intracellular A-particle antigen and DNA polymerase activity did not vary more than two-fold. The relative rate of A-particle synthesis in the treated cells, as judged by incorporation of radioactive amino acids into the major structural protein (P73), was also unchanged over the period of observation. Thus, the induction of type C virus particle formation in cultured neuroblastoma cells had no detectable effect on the quantity, synthesis rate, or location of intracisternal type A particles."} {"id": "PMID:183021", "title": "DNA-binding proteins induced by herpes simplex virus type 2 in HEp-2 cells.", "content": "Affinity chromatography on single-stranded and double-stranded DNA-cellulose indicates that 12 proteins previously identified from herpes simplex virus type 2-infected cells, ranging in molecular weight from 28 X 10(3) to 186 X 10(3), bind to DNA-cellulose. The DNA-binding proteins found in infected cells differed in relative binding strengths for denatured DNA-cellulose. The virus specificity of these DNA-binding proteins was further studied by comparison with DNA-binding proteins isolated from mock-infected cells, and by immunoprecipitation of infected-cell DNA-binding proteins with antisera specific for viral antigens. The promise this technique holds for the purification and study of polypeptides involved in virus DNA replication, recombination, or repair is discussed.", "contents": "DNA-binding proteins induced by herpes simplex virus type 2 in HEp-2 cells. Affinity chromatography on single-stranded and double-stranded DNA-cellulose indicates that 12 proteins previously identified from herpes simplex virus type 2-infected cells, ranging in molecular weight from 28 X 10(3) to 186 X 10(3), bind to DNA-cellulose. The DNA-binding proteins found in infected cells differed in relative binding strengths for denatured DNA-cellulose. The virus specificity of these DNA-binding proteins was further studied by comparison with DNA-binding proteins isolated from mock-infected cells, and by immunoprecipitation of infected-cell DNA-binding proteins with antisera specific for viral antigens. The promise this technique holds for the purification and study of polypeptides involved in virus DNA replication, recombination, or repair is discussed."} {"id": "PMID:183022", "title": "Polyadenylic acid in the genomic RNA of mengovirus.", "content": "The polyadenylic acid contained in 35S mengovirus RNA produced in infected BHK-21 cells contained approximately 94% AMP and was estimated to contain an average of 50 to 55 nucleotides. The polyadenylic acid is placed at the 3'-end of the genomic RNA based on the presence of significant levels of [3H]adenosine in complete alkali or RNase T2 digests of polyadenylic acid from [3H]adenosine-labeled 35S viral RNA.", "contents": "Polyadenylic acid in the genomic RNA of mengovirus. The polyadenylic acid contained in 35S mengovirus RNA produced in infected BHK-21 cells contained approximately 94% AMP and was estimated to contain an average of 50 to 55 nucleotides. The polyadenylic acid is placed at the 3'-end of the genomic RNA based on the presence of significant levels of [3H]adenosine in complete alkali or RNase T2 digests of polyadenylic acid from [3H]adenosine-labeled 35S viral RNA."} {"id": "PMID:183023", "title": "Interaction of liposomes with subviral particles of poliovirus type 2 and rhinovirus type 2.", "content": "Subviral particles (\"A particles\") were produced from rhinovirus type 2 by treatment with acid and from poliovirus type 2 by incubation at 37 degrees C in a low-ionic-strength buffer. A particles, but not virions, adsorbed to liposomes. It is proposed that these reactions may provide an in vitro model for two early steps of infection.", "contents": "Interaction of liposomes with subviral particles of poliovirus type 2 and rhinovirus type 2. Subviral particles (\"A particles\") were produced from rhinovirus type 2 by treatment with acid and from poliovirus type 2 by incubation at 37 degrees C in a low-ionic-strength buffer. A particles, but not virions, adsorbed to liposomes. It is proposed that these reactions may provide an in vitro model for two early steps of infection."} {"id": "PMID:183024", "title": "Radioisotopic labeling of human papovavirus (BK) by iodination and reductive alkylation.", "content": "Purified virions of the GS strain of the BK group of human papovaviruses were labeled with 125I using chloramine T or lactoperoxidase or with tritium using sodium borohydride. All viral polypeptides were labeled. Tryptic digests of iodinated VP1 were analyzed.", "contents": "Radioisotopic labeling of human papovavirus (BK) by iodination and reductive alkylation. Purified virions of the GS strain of the BK group of human papovaviruses were labeled with 125I using chloramine T or lactoperoxidase or with tritium using sodium borohydride. All viral polypeptides were labeled. Tryptic digests of iodinated VP1 were analyzed."} {"id": "PMID:183025", "title": "Lysine tRNA's associated with avian myeloblastosis virus 70S RNA.", "content": "The lysine tRNA released from the 70S RNA of avian myeloblastosis virus was separated by reversed-phase chromatography. All of the AAG-coding lysine tRNA's were present in the 70S-associated fraction; however, the AAA-coding lysine tRNA could not be detected. Chromatography of the lysine tRNA released at various temperatures did not show any preferential release of one AAG-coding species over another.", "contents": "Lysine tRNA's associated with avian myeloblastosis virus 70S RNA. The lysine tRNA released from the 70S RNA of avian myeloblastosis virus was separated by reversed-phase chromatography. All of the AAG-coding lysine tRNA's were present in the 70S-associated fraction; however, the AAA-coding lysine tRNA could not be detected. Chromatography of the lysine tRNA released at various temperatures did not show any preferential release of one AAG-coding species over another."} {"id": "PMID:183026", "title": "Hepatic adenomata with type 1 glycogen storage disease.", "content": "In older patients with glucose-6-phosphatase deficiency adenomatous nodules develop within the liver parenchyma. Investigation of eight such patients, age 3 to 28 years, using radioisotopic scans, has demonstrated areas of depressed isotope uptake in the liver in all except the one preteenaged child. Three patients were further studied with hepatic angiograms and liver biopsy specimens. A diffuse nodularity, more widespread than apparent on isotopic scans, was demonstrated on angiograms. Although initial histologic study in each case showed adenomatous tissue without evidence of neoplasm, the development of hepatocellular carcinoma in one of our patients and in others from the literature suggests that the nodules may be premalignant.", "contents": "Hepatic adenomata with type 1 glycogen storage disease. In older patients with glucose-6-phosphatase deficiency adenomatous nodules develop within the liver parenchyma. Investigation of eight such patients, age 3 to 28 years, using radioisotopic scans, has demonstrated areas of depressed isotope uptake in the liver in all except the one preteenaged child. Three patients were further studied with hepatic angiograms and liver biopsy specimens. A diffuse nodularity, more widespread than apparent on isotopic scans, was demonstrated on angiograms. Although initial histologic study in each case showed adenomatous tissue without evidence of neoplasm, the development of hepatocellular carcinoma in one of our patients and in others from the literature suggests that the nodules may be premalignant."} {"id": "PMID:183027", "title": "Positive differential heterophile antibody test. Persistence in a symptomatic patient.", "content": "A patient who had documented mononucleosis in June 1971 has been persistently symptomatic since that time, with easy fatigability and weight loss. He has also had a positive differential heterophile antibody test for mononucleosis for 14 months. Although no evidence for active Estein-Barr virus (EBV) infection was discovered, the possibility of a chronic EBV infection is discussed.", "contents": "Positive differential heterophile antibody test. Persistence in a symptomatic patient. A patient who had documented mononucleosis in June 1971 has been persistently symptomatic since that time, with easy fatigability and weight loss. He has also had a positive differential heterophile antibody test for mononucleosis for 14 months. Although no evidence for active Estein-Barr virus (EBV) infection was discovered, the possibility of a chronic EBV infection is discussed."} {"id": "PMID:183028", "title": "Hepatic abscess. Diagnosis in the adult by total body opacification.", "content": "Two adults had the hypovascular nature of their hepatic abscesses ascertained by total body opacification. In one, total body opacification identified the hypovascular nature of the lesion, facilitating its differentiation from vascular hepatoma. In the other, the clinical diagnosis was acute cholecystitis with empyema of the gallbladder, and the liver was normal to inspection and palpation at celiotomy. Total body opacification may be helpful in the examination of abdominal masses.", "contents": "Hepatic abscess. Diagnosis in the adult by total body opacification. Two adults had the hypovascular nature of their hepatic abscesses ascertained by total body opacification. In one, total body opacification identified the hypovascular nature of the lesion, facilitating its differentiation from vascular hepatoma. In the other, the clinical diagnosis was acute cholecystitis with empyema of the gallbladder, and the liver was normal to inspection and palpation at celiotomy. Total body opacification may be helpful in the examination of abdominal masses."} {"id": "PMID:183032", "title": "Clostridium perfringens exotoxins. III. Binding of theta-toxin to erythrocyte membrane.", "content": "When Clostridium perfringens theta-toxin was incubated with sheep erythrocytes the toxin activity disappeared before lysis, the fact of which suggests fixation of the toxin to erythrocyte membranes. 2. Theta-Toxin lost its activity by binding to cell membranes, and the membrane constituted inhibitor of theta-hemolysis was neither a protein, a carbohydrate nor a phosphatide, but was cholesterol. From these results this report proposes that the theta-toxin binding site of erythrocytes should be cholesterol.", "contents": "Clostridium perfringens exotoxins. III. Binding of theta-toxin to erythrocyte membrane. When Clostridium perfringens theta-toxin was incubated with sheep erythrocytes the toxin activity disappeared before lysis, the fact of which suggests fixation of the toxin to erythrocyte membranes. 2. Theta-Toxin lost its activity by binding to cell membranes, and the membrane constituted inhibitor of theta-hemolysis was neither a protein, a carbohydrate nor a phosphatide, but was cholesterol. From these results this report proposes that the theta-toxin binding site of erythrocytes should be cholesterol."} {"id": "PMID:183033", "title": "Vertical transmission of type I and type 2 Herpes simplex virus infection in hamsters.", "content": "The relation of type 2 herpes simplex virus infection during the several stages of embryogenesis of hamster was examined using histopathological and immunofluorescent techniques. The comparative investigation between type 2 and type 1 was done. Both types of herpes simplex virus caused placental lesions and vertical transmission in fetuses when the virus was inoculated intravenously into pregnant hamsters at the middle and late stage of gestation.", "contents": "Vertical transmission of type I and type 2 Herpes simplex virus infection in hamsters. The relation of type 2 herpes simplex virus infection during the several stages of embryogenesis of hamster was examined using histopathological and immunofluorescent techniques. The comparative investigation between type 2 and type 1 was done. Both types of herpes simplex virus caused placental lesions and vertical transmission in fetuses when the virus was inoculated intravenously into pregnant hamsters at the middle and late stage of gestation."} {"id": "PMID:183034", "title": "Temporal analysis of cellular cytotoxicity and humoral factors during progession and regression of Rous sarcomas in Japanese quails.", "content": "Temporal appearance of cellular cytotoxicity and humoral activities including blocking and arming activities during the entire course of Rous sarcoma development in Japanese quails was examined by microcytotoxicity assay with comparison of animals bearing regressing tumors induced by a moderate dose of virus (regressors) and animals bearing growing tumors induced by a large dose of virus (progressors). Cellular cytotoxicity of the spleen cells in regressors was detected in a biphasic pattern; the first phase being observed as early as 3-5 days post inoculation (p.i.), followed by an eclipse period between 7-10 days p.i. which was the time of active tumor growth, and the second phase occurring after 12 days p.i. when the tumor had attained the maximum size. In progressors, only the first phase was observed. Instead, a stimulatory effect of the spleen cells on growth of target cells was noticed. Arming activity which confers cytotoxic activity on the normal spleen cells was demonstrated in the sera of regressors in the similar biphasic pattern as the cellular cytotoxicity; the early activity being present at 3 days p.i., and the late one after 19 days p.i. The former was detected by pre-incubation of serum with effector cells in microcytotoxicity assay and the latter by pre-incubation with target cells. In progressors, only the early arming activity which reacts with effector cells was demonstrated. Blocking activity which abrogates cellular cytotoxicity was demonstrated in both regressors and progressors but in different patterns of appearance, that is, blocking activity in regressors was only transiently demonstrated only by pre-incubation with effector cells at the time of maximum tumor growth, while the activity in progressors seemed to persist after the tumor reached the maximum size. Since the earlier activity was found to be effective at effector cell level, and the later one at both effector and target cell levels, participation of blocking factors of different types in progressors was also suggested.", "contents": "Temporal analysis of cellular cytotoxicity and humoral factors during progession and regression of Rous sarcomas in Japanese quails. Temporal appearance of cellular cytotoxicity and humoral activities including blocking and arming activities during the entire course of Rous sarcoma development in Japanese quails was examined by microcytotoxicity assay with comparison of animals bearing regressing tumors induced by a moderate dose of virus (regressors) and animals bearing growing tumors induced by a large dose of virus (progressors). Cellular cytotoxicity of the spleen cells in regressors was detected in a biphasic pattern; the first phase being observed as early as 3-5 days post inoculation (p.i.), followed by an eclipse period between 7-10 days p.i. which was the time of active tumor growth, and the second phase occurring after 12 days p.i. when the tumor had attained the maximum size. In progressors, only the first phase was observed. Instead, a stimulatory effect of the spleen cells on growth of target cells was noticed. Arming activity which confers cytotoxic activity on the normal spleen cells was demonstrated in the sera of regressors in the similar biphasic pattern as the cellular cytotoxicity; the early activity being present at 3 days p.i., and the late one after 19 days p.i. The former was detected by pre-incubation of serum with effector cells in microcytotoxicity assay and the latter by pre-incubation with target cells. In progressors, only the early arming activity which reacts with effector cells was demonstrated. Blocking activity which abrogates cellular cytotoxicity was demonstrated in both regressors and progressors but in different patterns of appearance, that is, blocking activity in regressors was only transiently demonstrated only by pre-incubation with effector cells at the time of maximum tumor growth, while the activity in progressors seemed to persist after the tumor reached the maximum size. Since the earlier activity was found to be effective at effector cell level, and the later one at both effector and target cell levels, participation of blocking factors of different types in progressors was also suggested."} {"id": "PMID:183040", "title": "[Gene frequencies of red cell adenylate kinase and adenosine deaminase in the population of Northern Bavaria (Germany) (author's transl)].", "content": "Within a population sample of 2,000 blood donors in Northern Bavaria the AK- and ADA-polymorphisms have been investigated. The calculated gene frequencies are: AK1=0,9665; AK2=0,333; AK3=0,0003; AKA1=0,9453; ADA2=0,0548.", "contents": "[Gene frequencies of red cell adenylate kinase and adenosine deaminase in the population of Northern Bavaria (Germany) (author's transl)]. Within a population sample of 2,000 blood donors in Northern Bavaria the AK- and ADA-polymorphisms have been investigated. The calculated gene frequencies are: AK1=0,9665; AK2=0,333; AK3=0,0003; AKA1=0,9453; ADA2=0,0548."} {"id": "PMID:183051", "title": "Redistribution of immunoglobulin receptors on human neutrophils and its relationship to the release of lysosomal enzymes;.", "content": "Release of the lysosomal enzyme beta-glucuronidase from human neutrophils was induced by IgG or its Fc fragment, aggregated by immune precipitation or by coating on latex particles. Such release was inhibited when the cells were preincubated with free IgG or Fc fragments; F(ab')2 fragments were ineffective in both inducing and inhibiting beta-glucuronidase release. Neutrophils incubated with IgG or Fc fragments, when challenged with anti-IgG antibody, released lysosomal enzymes without the release of the cytoplasmic marker lactic dehydrogenase; These studies indicate that human neutrophils have surface receptors for the Fc portion of IgG. Neutrophils treated with IgG or its Fc fragment and subsequently with fluorescein- or ferritin-labeled anti-IgG showed binding of Fc or IgG to the cell membrane. Under suitable conditions, polar capping of labeled antibody was seen by fluorescence or electron microscopy. These studies suggest that the immunoglobulin receptors on neutrophils are redistributed when they are cross-linked with antibody. Fluidity of the membrane receptors appeared to be time and temperature dependent. Compounds such as 2-deoxyglucose, colchicine, and cyclic AMP, which inhibit the release of lysosomal enzymes, also inhibited the redistribution of the surface receptors. Cytochalasin B, an agent which increases the release, was found to increase the receptor redistribution; The relationship between the release of lysosomal enzymes and receptor mobility is discussed;", "contents": "Redistribution of immunoglobulin receptors on human neutrophils and its relationship to the release of lysosomal enzymes;. Release of the lysosomal enzyme beta-glucuronidase from human neutrophils was induced by IgG or its Fc fragment, aggregated by immune precipitation or by coating on latex particles. Such release was inhibited when the cells were preincubated with free IgG or Fc fragments; F(ab')2 fragments were ineffective in both inducing and inhibiting beta-glucuronidase release. Neutrophils incubated with IgG or Fc fragments, when challenged with anti-IgG antibody, released lysosomal enzymes without the release of the cytoplasmic marker lactic dehydrogenase; These studies indicate that human neutrophils have surface receptors for the Fc portion of IgG. Neutrophils treated with IgG or its Fc fragment and subsequently with fluorescein- or ferritin-labeled anti-IgG showed binding of Fc or IgG to the cell membrane. Under suitable conditions, polar capping of labeled antibody was seen by fluorescence or electron microscopy. These studies suggest that the immunoglobulin receptors on neutrophils are redistributed when they are cross-linked with antibody. Fluidity of the membrane receptors appeared to be time and temperature dependent. Compounds such as 2-deoxyglucose, colchicine, and cyclic AMP, which inhibit the release of lysosomal enzymes, also inhibited the redistribution of the surface receptors. Cytochalasin B, an agent which increases the release, was found to increase the receptor redistribution; The relationship between the release of lysosomal enzymes and receptor mobility is discussed;"} {"id": "PMID:183052", "title": "An ultrastructural study of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus.", "content": "Outbred Swiss mice 3 to 4 weeks of age were injected intracerebrally with wild-type vesicular stomatitis virus or its temperature-sensitive (ts) mutants ts 11, ts 22, ts 31, and ts 41. Brain and spinal cord were then studied for pathologic changes by electron microscopy. All mice infected with wild-type vesicular stomatitis virus died within 2 days of inoculation. Diffuse ependymal alterations often culminating in necrosis in brain and especially spinal cord and rare foci of necrosis and mononuclear cell infiltration in the injected hemisphere were the main pathologic changes in these animals. In contrast, mice infected intracerebrally with ts 22 and ts 31 showed their first clinical signs, consisting of hind limb paralysis, on day 4 and did not die until day 7 or 8 after inoculation. Ependymal alterations were of less severe degree in these animals, whereas the most striking changes were those of status spongiosus limited to the gray matter of the spinal cord. Such status spongiosus was mainly due to ballooning of dendrites and astrocytic processes, although myelin and neurons were also occasionally involved. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and failed to show significant pathologic features at 4 and 8 days after intracerebral inoculation. This study would indicate that some ts mutants of vesicular stomatitis virus are capable of altering the fulminating disease produced by the parent virus and of producing strikingly different pathologic changes.", "contents": "An ultrastructural study of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus. Outbred Swiss mice 3 to 4 weeks of age were injected intracerebrally with wild-type vesicular stomatitis virus or its temperature-sensitive (ts) mutants ts 11, ts 22, ts 31, and ts 41. Brain and spinal cord were then studied for pathologic changes by electron microscopy. All mice infected with wild-type vesicular stomatitis virus died within 2 days of inoculation. Diffuse ependymal alterations often culminating in necrosis in brain and especially spinal cord and rare foci of necrosis and mononuclear cell infiltration in the injected hemisphere were the main pathologic changes in these animals. In contrast, mice infected intracerebrally with ts 22 and ts 31 showed their first clinical signs, consisting of hind limb paralysis, on day 4 and did not die until day 7 or 8 after inoculation. Ependymal alterations were of less severe degree in these animals, whereas the most striking changes were those of status spongiosus limited to the gray matter of the spinal cord. Such status spongiosus was mainly due to ballooning of dendrites and astrocytic processes, although myelin and neurons were also occasionally involved. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and failed to show significant pathologic features at 4 and 8 days after intracerebral inoculation. This study would indicate that some ts mutants of vesicular stomatitis virus are capable of altering the fulminating disease produced by the parent virus and of producing strikingly different pathologic changes."} {"id": "PMID:183053", "title": "Ultrastructural study of contraction of pulmonary vascular smooth muscle cells.", "content": "The pulmonary vessels of rats treated with fulvine were studied electron microscopically for morphologic signs of contraction of smooth muscle cells. Except for a number of indirect indications of vasoconstriction such as medial smooth muscle cell hypertrophy and excessive crenation of elastic laminae, conspicuous smooth muscle cell excrescences were observed and were interpreted to be a direct result of contraction. The close relationship between contraction and smooth muscle cell excrescences was confirmed by their simultaneous occurrence within 1 minute after administration of histamine to isolated perfused guinea pig lungs. The images of pulmonary vessels of rats with prolonged survival times after fulvine administration suggested a gradual increase in the size of the excrescences with a simultaneous degeneration of their cytoplasmic content, and in some cases their eventual detachment from the main cell body. The latter changes were possibly associated with the widespread vasculitis that often occurred at longer intervals after fulvine application. The smooth muscle cell excrescences in pulmonary veins were generally much more prominent than those in pulmonary arteries. This difference was probably caused by the more rigid structure of the arterial wall whcih prevented the formation of large excrescences. The mechanism of the formation of smooth muscle cell excrescences, their possible general validity as markers of vascular smooth muscle cell contraction, and the implications for the mechanism of action of fulvine are briefly discussed.", "contents": "Ultrastructural study of contraction of pulmonary vascular smooth muscle cells. The pulmonary vessels of rats treated with fulvine were studied electron microscopically for morphologic signs of contraction of smooth muscle cells. Except for a number of indirect indications of vasoconstriction such as medial smooth muscle cell hypertrophy and excessive crenation of elastic laminae, conspicuous smooth muscle cell excrescences were observed and were interpreted to be a direct result of contraction. The close relationship between contraction and smooth muscle cell excrescences was confirmed by their simultaneous occurrence within 1 minute after administration of histamine to isolated perfused guinea pig lungs. The images of pulmonary vessels of rats with prolonged survival times after fulvine administration suggested a gradual increase in the size of the excrescences with a simultaneous degeneration of their cytoplasmic content, and in some cases their eventual detachment from the main cell body. The latter changes were possibly associated with the widespread vasculitis that often occurred at longer intervals after fulvine application. The smooth muscle cell excrescences in pulmonary veins were generally much more prominent than those in pulmonary arteries. This difference was probably caused by the more rigid structure of the arterial wall whcih prevented the formation of large excrescences. The mechanism of the formation of smooth muscle cell excrescences, their possible general validity as markers of vascular smooth muscle cell contraction, and the implications for the mechanism of action of fulvine are briefly discussed."} {"id": "PMID:183054", "title": "An ultrastructural study of the glomerular slit diaphragm in New Zealand black/white mice.", "content": "Glomerular epithelial slit alterations and their relation to proteinuria have not been studied in detail in New Zealand Black/White (NZB/W) mice. The kidneys of proteinuric and nonproteinuric female NZB/W mice and normal Swiss albino mice were perfusion-fixed with tannic acid-glutaraldehyde and studied by light and electron microscopy. Semiquantitative studies were performed on full montages of glomeruli enlarged 10,000 times. Fine structural alterations of the epithelial slits, with emphasis on the slit diaphragm, were studied on semiserial thin sections. Proteinuric NZB/W mice with features of membraneous nephropathy exhibited: (1) wedging of electron-dense deposits below the slit diaphragm, (2) enlargement and distortion of interpedicel spaces, (3) displacement, folding, and stacking of slit diaphragms, (4) formation of occluding junctional complexes in residual slits, and (5) variable loss of foot processes. Similar alterations were not observed in controls or nonproteinuric NZB/W mice, including animals having complexes inglomerular mesangia but not in epithlialslits. These studies show that in NZB/W mice, abnormal protein excretion is associated with structural modification of the slit pore and suggest a role for such a component in the process of protein ex", "contents": "An ultrastructural study of the glomerular slit diaphragm in New Zealand black/white mice. Glomerular epithelial slit alterations and their relation to proteinuria have not been studied in detail in New Zealand Black/White (NZB/W) mice. The kidneys of proteinuric and nonproteinuric female NZB/W mice and normal Swiss albino mice were perfusion-fixed with tannic acid-glutaraldehyde and studied by light and electron microscopy. Semiquantitative studies were performed on full montages of glomeruli enlarged 10,000 times. Fine structural alterations of the epithelial slits, with emphasis on the slit diaphragm, were studied on semiserial thin sections. Proteinuric NZB/W mice with features of membraneous nephropathy exhibited: (1) wedging of electron-dense deposits below the slit diaphragm, (2) enlargement and distortion of interpedicel spaces, (3) displacement, folding, and stacking of slit diaphragms, (4) formation of occluding junctional complexes in residual slits, and (5) variable loss of foot processes. Similar alterations were not observed in controls or nonproteinuric NZB/W mice, including animals having complexes inglomerular mesangia but not in epithlialslits. These studies show that in NZB/W mice, abnormal protein excretion is associated with structural modification of the slit pore and suggest a role for such a component in the process of protein ex"} {"id": "PMID:183055", "title": "Assessment of skeletal aging using the 3H-proline topographic labeling method.", "content": "The present report represents an extension of initial 3H-proline autoradiographic studies designed to provide, at both the cytologic and histologic levels, an indelible topographic record of skeletal events in aging mice. 3H-proline was administered in multiple time-spaced doses and the animals were serially killed between 6 and 14 days later. Whole femora sectioned in longitudinal and three cross-sectional planes were prepared for autoradiography and subsequent grain count and micrometric analysis of the silver topographic bands which form over mineralizing surfaces. These bands, coincidental with the cellular uptake and turnover of radiotracer, allowed for the assessment of cellular rates of labeled matrical precursor production and deposition from which the processes of bone growth and remodeling and the effects of aging on the skeletal system can be evaluated. In addition, composite tracings of topographic data derived from multiple sections prepared at different geometric planes allowed for three-dimensional mapping of skeletal events. The results showed that the matrical rates of bone production in micrometers per day varied considerably from one surface to the next and decreased significantly with increasing age. The rates at posterior periosteal surfaces were twice those observed at the anterior periosteal surfaces of 5-week-old mice. By 26 weeks the rates decreased to 1/8 times, respectively. Between 52 and 104 weeks of age, no significant matrix production occurred at the periosteal surfaces. Endosteal activity was greater than twice the posterior periosteal rate at 5 weeks, 1/4 times at 26 weeks, and 1/8 times at 104 weeks of age. It was concluded that endosteal matrix production continued throughout life via active remodeling processes, but periosteal activity was turned-off by 52 weeks. Furthermore, the study unexpectedly showed that in old animals, subendosteal bone formation exhibiting hematopoietic activity is activated at 52 weeks in focal areas...", "contents": "Assessment of skeletal aging using the 3H-proline topographic labeling method. The present report represents an extension of initial 3H-proline autoradiographic studies designed to provide, at both the cytologic and histologic levels, an indelible topographic record of skeletal events in aging mice. 3H-proline was administered in multiple time-spaced doses and the animals were serially killed between 6 and 14 days later. Whole femora sectioned in longitudinal and three cross-sectional planes were prepared for autoradiography and subsequent grain count and micrometric analysis of the silver topographic bands which form over mineralizing surfaces. These bands, coincidental with the cellular uptake and turnover of radiotracer, allowed for the assessment of cellular rates of labeled matrical precursor production and deposition from which the processes of bone growth and remodeling and the effects of aging on the skeletal system can be evaluated. In addition, composite tracings of topographic data derived from multiple sections prepared at different geometric planes allowed for three-dimensional mapping of skeletal events. The results showed that the matrical rates of bone production in micrometers per day varied considerably from one surface to the next and decreased significantly with increasing age. The rates at posterior periosteal surfaces were twice those observed at the anterior periosteal surfaces of 5-week-old mice. By 26 weeks the rates decreased to 1/8 times, respectively. Between 52 and 104 weeks of age, no significant matrix production occurred at the periosteal surfaces. Endosteal activity was greater than twice the posterior periosteal rate at 5 weeks, 1/4 times at 26 weeks, and 1/8 times at 104 weeks of age. It was concluded that endosteal matrix production continued throughout life via active remodeling processes, but periosteal activity was turned-off by 52 weeks. Furthermore, the study unexpectedly showed that in old animals, subendosteal bone formation exhibiting hematopoietic activity is activated at 52 weeks in focal areas..."} {"id": "PMID:183056", "title": "Crystals, paracrystals, and rigid tubules in multiple sclerotic brain and spinal fluid.", "content": "Brain and spinal fluid were obtained post mortem from an individual with multiple sclerosis who died following carbon monoxide inhalation. Electron microscopic examination of the plaque region revealed a crystalline structure (repeat unit 380 to 410 A) within rough endoplasmic reticulum of astrocytes, a paracrystal (160 to 220 A) within the cytoplasm of astrocytes, and rigid tubules (outer diameter 320 to 450 A) within a cell in the lumen of a capillary. The paracrystal was enclosed by the glial fibrils. A second crystalline material was observed within cells in the 15,000 X g pellet from spinal fluid. The ultrastructural pattern of this second crystal was generated by three sets of parallel lines; a given set was intersected by the other two sets. The crystal had only two different repeat units (410 to 450 A; 310 to 350 A) since the smaller dimension was common for two sets of lines. The two crystals were large; the one in astrocytes had a length of 52,000 A and that in spinal fluid sediment was 62,000 A. These structures were observed in the one multiple sclerotic brain obtained at autopsy but were not detected in multiple sclerotic brains that had been frozen for extended periods. Plaque regions and grossly normal white matter were homogenized and the 1000 X g supernatant of this material was fractionated in a continuous CsCl-sucrose density gradient. Long tubules (320 to 500 A diameter) were observed in the 1.24 to 1.26 density region. The major proteins of the 1.24 to 1.26 fraction had molecular weights clustered at 40,000 to 45,000, 88,000 to 130,000, and 300,000.", "contents": "Crystals, paracrystals, and rigid tubules in multiple sclerotic brain and spinal fluid. Brain and spinal fluid were obtained post mortem from an individual with multiple sclerosis who died following carbon monoxide inhalation. Electron microscopic examination of the plaque region revealed a crystalline structure (repeat unit 380 to 410 A) within rough endoplasmic reticulum of astrocytes, a paracrystal (160 to 220 A) within the cytoplasm of astrocytes, and rigid tubules (outer diameter 320 to 450 A) within a cell in the lumen of a capillary. The paracrystal was enclosed by the glial fibrils. A second crystalline material was observed within cells in the 15,000 X g pellet from spinal fluid. The ultrastructural pattern of this second crystal was generated by three sets of parallel lines; a given set was intersected by the other two sets. The crystal had only two different repeat units (410 to 450 A; 310 to 350 A) since the smaller dimension was common for two sets of lines. The two crystals were large; the one in astrocytes had a length of 52,000 A and that in spinal fluid sediment was 62,000 A. These structures were observed in the one multiple sclerotic brain obtained at autopsy but were not detected in multiple sclerotic brains that had been frozen for extended periods. Plaque regions and grossly normal white matter were homogenized and the 1000 X g supernatant of this material was fractionated in a continuous CsCl-sucrose density gradient. Long tubules (320 to 500 A diameter) were observed in the 1.24 to 1.26 density region. The major proteins of the 1.24 to 1.26 fraction had molecular weights clustered at 40,000 to 45,000, 88,000 to 130,000, and 300,000."} {"id": "PMID:183062", "title": "The malignancy of bronchial adenoma.", "content": "The literature on bronchial adenoma has been reviewed and controversy found to exist about certain aspects of these tumors, particularly their malignancy. A retrospective study of 79 cases managed in Edinburgh since 1946 is presented. Seventy-one were of the carcinoid type, 7 were adenoid cystic carcinomas, and there was a single example of mucoepidermoid carcinoma. All types show a definite malignant potential, greatest in the rare mucoepidermoid tumor and least in the common carcinoid variety. Adenoid cystic carcinoma occupied an intermediate position in frequency and malignancy.", "contents": "The malignancy of bronchial adenoma. The literature on bronchial adenoma has been reviewed and controversy found to exist about certain aspects of these tumors, particularly their malignancy. A retrospective study of 79 cases managed in Edinburgh since 1946 is presented. Seventy-one were of the carcinoid type, 7 were adenoid cystic carcinomas, and there was a single example of mucoepidermoid carcinoma. All types show a definite malignant potential, greatest in the rare mucoepidermoid tumor and least in the common carcinoid variety. Adenoid cystic carcinoma occupied an intermediate position in frequency and malignancy."} {"id": "PMID:183063", "title": "Immune reactivity in primary carcinoma of the lung and its relation to prognosis.", "content": "Detailed studies of immune reactivity were performed in 154 patients with primary lung cancer, 20 patients with benign thoracic lesions, and 109 healthy persons. Reactions to the 2,4-dinitrochlorobenzene (DNCB) skin test were postive in 73 per cent of patients with lung cancer and all (100 per cent) of the patients with benign disease (p less than 0.05). The incidence of DNCB reactions was 78 per cent for Stage I and II cancers (37 patinets), 73 per cent for resectable Stage III cancer (22 patients), and 66 per cent in patients with unresectable or inoperable Stage III cancer. DNCB reactivity showed a relationship to primary histology. The incidence of DNCB positive reactions was 80 per cent in patients with epidermold carcinoma versus 57 per cent in patients with adenocarcinoma, 64 per cent in patients with oat cell cancer, and 80 per cent in patients with terminal bronchiolar carcinoma. In vitro immune studeis correlated best with stage of disease. These included the absolute lymphocyte count and absolute T cell count and lymphoxyte stimulation witalen A (Com A). These values were in the normal range in patients with Stage I cancer but were significantly depressed in patients with Stage III cancer. Svrvival curves were plotted in patients with Stage III disease according to the responses to three immune parameters: DNCB, absolute lymphocyte count, and PHS stimulation. Although patients with normal reactions generally had better survival rates, PHA responses showed the most significant correlation to survival. These tests support the usefulness of immune testing as an additional parameter of assessing biological risk in patients with primary lung cancer.", "contents": "Immune reactivity in primary carcinoma of the lung and its relation to prognosis. Detailed studies of immune reactivity were performed in 154 patients with primary lung cancer, 20 patients with benign thoracic lesions, and 109 healthy persons. Reactions to the 2,4-dinitrochlorobenzene (DNCB) skin test were postive in 73 per cent of patients with lung cancer and all (100 per cent) of the patients with benign disease (p less than 0.05). The incidence of DNCB reactions was 78 per cent for Stage I and II cancers (37 patinets), 73 per cent for resectable Stage III cancer (22 patients), and 66 per cent in patients with unresectable or inoperable Stage III cancer. DNCB reactivity showed a relationship to primary histology. The incidence of DNCB positive reactions was 80 per cent in patients with epidermold carcinoma versus 57 per cent in patients with adenocarcinoma, 64 per cent in patients with oat cell cancer, and 80 per cent in patients with terminal bronchiolar carcinoma. In vitro immune studeis correlated best with stage of disease. These included the absolute lymphocyte count and absolute T cell count and lymphoxyte stimulation witalen A (Com A). These values were in the normal range in patients with Stage I cancer but were significantly depressed in patients with Stage III cancer. Svrvival curves were plotted in patients with Stage III disease according to the responses to three immune parameters: DNCB, absolute lymphocyte count, and PHS stimulation. Although patients with normal reactions generally had better survival rates, PHA responses showed the most significant correlation to survival. These tests support the usefulness of immune testing as an additional parameter of assessing biological risk in patients with primary lung cancer."} {"id": "PMID:183064", "title": "Results of treatment of primary carcinoma of the lung. Analysis of 3,000 cases.", "content": "Three thousand patients with primary carcinoma of the lung entered in the Armed Forces Central Medical Registry are reported. Forty-one per cent had squamous cell, 28.5 per cent adenocarcinoma, 25.2 per cent small cell/undifferentiated, and 4.9 per cent miscellaneous cell types. When first seen, 71.1 per cent had no organ metastases and 50.6 per cent no lymph node metastases. Over-all survival rate was 18.2 per cent at 5 years and 14.5 per cent at 10 years. Survival following definitive resection, palliative resection, definitive radiation, palliative radiation, and chemotherapy was determined both in the presence of mediastinal nodal involvement and in the absence of mediatinal nodal involvement. Where resection for cure could be carried out, 5 year survival rates of 48.8 per cent were possible. The factors affecting this improved outlook in our military population are discussed and, in general, appear to be related to a ready accessibility of medical care and the necessity, because of global commitments, of establishing an early diagnosis. Cell type ecerted some influence on survival, but the major determinant appeared to be the absence of involved nodes at the time of the operation.", "contents": "Results of treatment of primary carcinoma of the lung. Analysis of 3,000 cases. Three thousand patients with primary carcinoma of the lung entered in the Armed Forces Central Medical Registry are reported. Forty-one per cent had squamous cell, 28.5 per cent adenocarcinoma, 25.2 per cent small cell/undifferentiated, and 4.9 per cent miscellaneous cell types. When first seen, 71.1 per cent had no organ metastases and 50.6 per cent no lymph node metastases. Over-all survival rate was 18.2 per cent at 5 years and 14.5 per cent at 10 years. Survival following definitive resection, palliative resection, definitive radiation, palliative radiation, and chemotherapy was determined both in the presence of mediastinal nodal involvement and in the absence of mediatinal nodal involvement. Where resection for cure could be carried out, 5 year survival rates of 48.8 per cent were possible. The factors affecting this improved outlook in our military population are discussed and, in general, appear to be related to a ready accessibility of medical care and the necessity, because of global commitments, of establishing an early diagnosis. Cell type ecerted some influence on survival, but the major determinant appeared to be the absence of involved nodes at the time of the operation."} {"id": "PMID:183065", "title": "Ultrastructural cytochemistry of platelets and megakaryocytes in the carcinoid syndrome.", "content": "Platelets and megakaryocytes from 11 patients with the carcinoid syndrome have been studied by transmission electron microscopy. Cells fixed in phosphate-buffered glutaraldehyde are oval to discoid, with pseudopods, a dilated open-channel system, and a prominent dense tubular system as defined by peroxidase activity and alkaline bismuth stain. Atypical with hexagonal lattices and treaded substructures and large (diameter greater than 0.5 mum), phosphatase-positive, debris-containing vacuoles are four times more numerous than in normal platelets. Incubation of platelets in a 0.05% suspension of latex results in particle incorporation into phagosomes and the debris-containing vacuoles. Molybdate-dichromate stain reveals two classes of dense bodies, one of which (with a reticular core) is 20 times more numerous than in normal platelets. Bone marrow megakaryocytes lack both dense bodies and debris vacuoles analogous to those found in circulating platelets. These results suggest autophagy or endocytosis abnormalities and provide evidence for multiple types of dense bodies in carcinoid platelets.", "contents": "Ultrastructural cytochemistry of platelets and megakaryocytes in the carcinoid syndrome. Platelets and megakaryocytes from 11 patients with the carcinoid syndrome have been studied by transmission electron microscopy. Cells fixed in phosphate-buffered glutaraldehyde are oval to discoid, with pseudopods, a dilated open-channel system, and a prominent dense tubular system as defined by peroxidase activity and alkaline bismuth stain. Atypical with hexagonal lattices and treaded substructures and large (diameter greater than 0.5 mum), phosphatase-positive, debris-containing vacuoles are four times more numerous than in normal platelets. Incubation of platelets in a 0.05% suspension of latex results in particle incorporation into phagosomes and the debris-containing vacuoles. Molybdate-dichromate stain reveals two classes of dense bodies, one of which (with a reticular core) is 20 times more numerous than in normal platelets. Bone marrow megakaryocytes lack both dense bodies and debris vacuoles analogous to those found in circulating platelets. These results suggest autophagy or endocytosis abnormalities and provide evidence for multiple types of dense bodies in carcinoid platelets."} {"id": "PMID:183069", "title": "[Etiological aspects regarding the development of laryngeal papillomas (author's transl)].", "content": "Papilloma of the larynx are virus-induced, benign neoplasmas. The virus belongs to the Papovavirus group and causes skin-warts, condylomata acuminata and papilloma of the mucous membranes. The close relation of these diseases is shown by a review of dermatologic and otologic literature and compared with own results.", "contents": "[Etiological aspects regarding the development of laryngeal papillomas (author's transl)]. Papilloma of the larynx are virus-induced, benign neoplasmas. The virus belongs to the Papovavirus group and causes skin-warts, condylomata acuminata and papilloma of the mucous membranes. The close relation of these diseases is shown by a review of dermatologic and otologic literature and compared with own results."} {"id": "PMID:183066", "title": "Treatment of senile dementia and cerebellar disorders with phthalazinol. Cyclic AMP-increasing agent, phthalazinol, in therapeutic trials in hitherto incurable morbid conditions (I).", "content": "Three patients suffering from presenile dementia and two patients suffering from senile dementia were treated with phthalazinol. A limited but definite improvement in attentiveness, vocabulary reception and psychologic attainment and also a limited but definite improvement in range of motion, gait and endurance were noted shortly after the treatment with phthalazinol and the progression of their dementia seemed to be temporarily retarded by phthalazinol. Seven patients suffering from parenchymatous cerebellar degeneration (late cortico-cerebellar atrophy) and four patients suffering from olivopontocerebellar atrophy were treated with phthalazinol. A relatively rapid, limited and sustained improvement of cerebellar functions, including those of speaking, writing and walking, was noted in almost all patients. Also, rigidity, akinetic tendency and abnormal posture seen in olivopontocerebellar atrophy fairly well responded to the treatment. Dysphagia, disturbance of micturition, and hypersecretion of saliva have also rapidly and completely disappeared in all cases. The cases with a long history responded relatively poorly, but the cases with a relatively short history responded quite strikingly to the therapy. No side effects were noted.", "contents": "Treatment of senile dementia and cerebellar disorders with phthalazinol. Cyclic AMP-increasing agent, phthalazinol, in therapeutic trials in hitherto incurable morbid conditions (I). Three patients suffering from presenile dementia and two patients suffering from senile dementia were treated with phthalazinol. A limited but definite improvement in attentiveness, vocabulary reception and psychologic attainment and also a limited but definite improvement in range of motion, gait and endurance were noted shortly after the treatment with phthalazinol and the progression of their dementia seemed to be temporarily retarded by phthalazinol. Seven patients suffering from parenchymatous cerebellar degeneration (late cortico-cerebellar atrophy) and four patients suffering from olivopontocerebellar atrophy were treated with phthalazinol. A relatively rapid, limited and sustained improvement of cerebellar functions, including those of speaking, writing and walking, was noted in almost all patients. Also, rigidity, akinetic tendency and abnormal posture seen in olivopontocerebellar atrophy fairly well responded to the treatment. Dysphagia, disturbance of micturition, and hypersecretion of saliva have also rapidly and completely disappeared in all cases. The cases with a long history responded relatively poorly, but the cases with a relatively short history responded quite strikingly to the therapy. No side effects were noted."} {"id": "PMID:183079", "title": "Evaluation of an automated procedure for primary screening of hyperlipoproteinemias.", "content": "An automated procedure for the determination of beta-plus-pre-beta-lipoprotein cholesterol is described and evaluated for mass screening of hyperlipoproteinemias. It is shown that this method fulfills the requirements for an ideal method for primary screening: it can be used in non-fasting samples, is capable of detecting hyperlipoproteinemias characterized by both cholesterol and/or triglyceride abnormalities, is fast, accurate and extremely inexpensive. Evidence is shown that the method is extremely useful for primary screening and, when tested in a coronary screening detection program, gave only 4% false positive and 3.4% false negative results.", "contents": "Evaluation of an automated procedure for primary screening of hyperlipoproteinemias. An automated procedure for the determination of beta-plus-pre-beta-lipoprotein cholesterol is described and evaluated for mass screening of hyperlipoproteinemias. It is shown that this method fulfills the requirements for an ideal method for primary screening: it can be used in non-fasting samples, is capable of detecting hyperlipoproteinemias characterized by both cholesterol and/or triglyceride abnormalities, is fast, accurate and extremely inexpensive. Evidence is shown that the method is extremely useful for primary screening and, when tested in a coronary screening detection program, gave only 4% false positive and 3.4% false negative results."} {"id": "PMID:183084", "title": "Therapeutic failure in familial type II hyperlipoproteinemia.", "content": "The extended use of diet and cholestyramine therapy in familial type II hyperlipoproteinemia was examined in patients who previously participated in a short-term, double-blind trial. A striking secondary failure in therapeutic response during 4 yr of use of this therapy was noted with plasma cholesterol rising an average of 15%. A 3 mo, out-patient, follow-up study designed to reinforce patient motivation and dietary and drug adherence resulted in a prompt but partial reversal of this therapeutic deterioration in 16 patients. Additional inpatient studies confirmed that patient noncompliance with the dietary regimen was the major factor responsible for the secondary failure. Cholestyramine together with a low cholesterol diet can be an effective agent in familial type II hyperlipoproteinemia, given a comprehensive program of out-patient follow-up with continued emphasis on dietary principles and drug adherence.", "contents": "Therapeutic failure in familial type II hyperlipoproteinemia. The extended use of diet and cholestyramine therapy in familial type II hyperlipoproteinemia was examined in patients who previously participated in a short-term, double-blind trial. A striking secondary failure in therapeutic response during 4 yr of use of this therapy was noted with plasma cholesterol rising an average of 15%. A 3 mo, out-patient, follow-up study designed to reinforce patient motivation and dietary and drug adherence resulted in a prompt but partial reversal of this therapeutic deterioration in 16 patients. Additional inpatient studies confirmed that patient noncompliance with the dietary regimen was the major factor responsible for the secondary failure. Cholestyramine together with a low cholesterol diet can be an effective agent in familial type II hyperlipoproteinemia, given a comprehensive program of out-patient follow-up with continued emphasis on dietary principles and drug adherence."} {"id": "PMID:183085", "title": "Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients.", "content": "A low-density lipoprotein turnover study was performed on six heteroxygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipo-proteniemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate (r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia.", "contents": "Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients. A low-density lipoprotein turnover study was performed on six heteroxygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipo-proteniemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate (r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia."} {"id": "PMID:183091", "title": "Declining mortality and improving survival from Wilms' tumor.", "content": "Mortality from kidney cancer in the United States declined dramatically over the period 1940-1969. This trend was nearly proportional to the increases in survival for 644 U.S. children reported to the End Results Group, National Cancer Institute. The improvements in survival occurred for all stages of disease and appeared to result from therapeutic advances rather than earlier detection. Total incidence trends showed no consistent change, but a shift toward female preponderance resembled that seen in the mortality statistics and suggests sex differences in etiology.", "contents": "Declining mortality and improving survival from Wilms' tumor. Mortality from kidney cancer in the United States declined dramatically over the period 1940-1969. This trend was nearly proportional to the increases in survival for 644 U.S. children reported to the End Results Group, National Cancer Institute. The improvements in survival occurred for all stages of disease and appeared to result from therapeutic advances rather than earlier detection. Total incidence trends showed no consistent change, but a shift toward female preponderance resembled that seen in the mortality statistics and suggests sex differences in etiology."} {"id": "PMID:183092", "title": "Acute leukemia in Burkitt lymphoma.", "content": "Burkitt lymphoma uncommonly presents as a acute leukemia. We describe the clinical course and findings of a 14-year-old female with Burkitt lymphoma who presented with acute leukemia. splenomegaly and an abdominal mass. She responded initially to prednisone alone and later achieved full remission with combination chemotherapy. Established morphologic criteria and clinical course were consistent with the diagnosis of Burkitt lymphoma (1), although B-cell determinants were not present on her tumor cells.", "contents": "Acute leukemia in Burkitt lymphoma. Burkitt lymphoma uncommonly presents as a acute leukemia. We describe the clinical course and findings of a 14-year-old female with Burkitt lymphoma who presented with acute leukemia. splenomegaly and an abdominal mass. She responded initially to prednisone alone and later achieved full remission with combination chemotherapy. Established morphologic criteria and clinical course were consistent with the diagnosis of Burkitt lymphoma (1), although B-cell determinants were not present on her tumor cells."} {"id": "PMID:183093", "title": "Simultaneous determinations of Fe, Cu, Zn, and Br concentrations in human tissue sections.", "content": "Proton-induced x-ray fluorescence has been used to determine the concentration of trace elements in human prostate and liver tissue samples. Ca, Fe, Cu, and Zn were observed in all specimens. Small amounts of Br were detected in most of the prostates, and in nearly half of the livers. The data indicate that the Fe content decreases in malignant liver tissues and the quantities of Cu and Zn are also decreased, but to a lesser extent.", "contents": "Simultaneous determinations of Fe, Cu, Zn, and Br concentrations in human tissue sections. Proton-induced x-ray fluorescence has been used to determine the concentration of trace elements in human prostate and liver tissue samples. Ca, Fe, Cu, and Zn were observed in all specimens. Small amounts of Br were detected in most of the prostates, and in nearly half of the livers. The data indicate that the Fe content decreases in malignant liver tissues and the quantities of Cu and Zn are also decreased, but to a lesser extent."} {"id": "PMID:183100", "title": "Effect of different carbon sources on the biosynthesis of polyunsaturated fatty acids of alpha-linolenic acid family in culture of minimal deviation hepatoma 7288 C cells.", "content": "The effect of three different carbon sources on the biosynthesis of polyunsaturated fatty acids of the alpha-linolenic acid series was investigated in hepatoma tissue culture (HTC) cells. Alpha linolenic acid was converted to higher homologs by a desaturating route that synthetized mainly 18:4 (delta6, 9, 12, 15), 20:4 (delta8, 11, 14, 17) and 20:5 (delta5, 8, 11, 14, 17) and an elongating route that produced 20:3 (delta11, 14, 17) and 20:4 (delta5, 11, 14, 17) acids. \"Fasting\" decreased both biosynthetic routes whereas glucose reactivated only the elongating pathway. Lactabumin hydrolysate enhanced significantly only the desaturating route whereas glycerol was inactive. Glucose and aminoacids increased similarly the incorporation of labeled alpha linolenic acid in the cells. The results are independent of hormonal effects.", "contents": "Effect of different carbon sources on the biosynthesis of polyunsaturated fatty acids of alpha-linolenic acid family in culture of minimal deviation hepatoma 7288 C cells. The effect of three different carbon sources on the biosynthesis of polyunsaturated fatty acids of the alpha-linolenic acid series was investigated in hepatoma tissue culture (HTC) cells. Alpha linolenic acid was converted to higher homologs by a desaturating route that synthetized mainly 18:4 (delta6, 9, 12, 15), 20:4 (delta8, 11, 14, 17) and 20:5 (delta5, 8, 11, 14, 17) and an elongating route that produced 20:3 (delta11, 14, 17) and 20:4 (delta5, 11, 14, 17) acids. \"Fasting\" decreased both biosynthetic routes whereas glucose reactivated only the elongating pathway. Lactabumin hydrolysate enhanced significantly only the desaturating route whereas glycerol was inactive. Glucose and aminoacids increased similarly the incorporation of labeled alpha linolenic acid in the cells. The results are independent of hormonal effects."} {"id": "PMID:183101", "title": "Interaction of aminoacyl-tRNA synthetases and tRNA: positive and negative cooperativity of their active centres.", "content": "The influence of tRNA on the kinetics of PP-ATP exchange and aminoacyl-tRNA formation catalysed by leucyl-, phenylalanyl-, and tryptophanyl-tRNA synthetases has been investigated. These enzymes were chosen because they belong to three main classes of quaternary structure alpha1, alpha2beta2 and alpha2, respectively. The present paper shows that the investigated synthetases manifest kinetic cooperativity of the active centres which is negative in the case of AAA formation and positive in the case of leucyl- and tryptophanyl-tRNA synthesis. The obtained data were interpreted with the aid of the trigger model of the enzyme.", "contents": "Interaction of aminoacyl-tRNA synthetases and tRNA: positive and negative cooperativity of their active centres. The influence of tRNA on the kinetics of PP-ATP exchange and aminoacyl-tRNA formation catalysed by leucyl-, phenylalanyl-, and tryptophanyl-tRNA synthetases has been investigated. These enzymes were chosen because they belong to three main classes of quaternary structure alpha1, alpha2beta2 and alpha2, respectively. The present paper shows that the investigated synthetases manifest kinetic cooperativity of the active centres which is negative in the case of AAA formation and positive in the case of leucyl- and tryptophanyl-tRNA synthesis. The obtained data were interpreted with the aid of the trigger model of the enzyme."} {"id": "PMID:183102", "title": "[Reaction capabilities and structure of poly(rG) and poly(rG)-poly(rC) in solution by the method of the kinetics of hydrogen ion exchange].", "content": "Data on the kinetics of 1H greater than 3H exchange between water and C(8)H groups of guanylic residues in the poly(rG) and poly poly(rG)-poly(rC) are presented. Furthermore, optical properties (CD spectra and hyperchromism) of neutral solutions of these polymers from 20 to 100 degrees C are described. It is shown that the exchange in poly(rG) within the temperature range from 20 to 80 degrees C proceeds faster than in rGMP. Within the temperature range from 20 to 40 degrees C such an acceleration of the exchange is observed also in poly(rG)-poly(rC). According to the ylide mechanism of the exchange reaction the observed accleration of the exchanged in in C(8)H groups of guanylic residues is considered as a consequence of an increase of the positive charge at N(7) atoms. This effect is due to formation of additional hydrogen bonds in which N(7) atoms take part. The exchange in poly(rG)-poly(rG) at temperatures hihger than 75 degrees C, when these additional hydrogen bonds are absent, proceeds more slowly than in rGMP. Such picture is usual in other previously studied polynucleotides whose structure in solution is stabilized only by Watson - Crick hydrogen bonds and stacking interactions. The data obtained support a Guschelbauer's model of the four-stranded stranded poly(rG). They also indicate the posibility of associates formation in poly(rG)-poly(rC) solutions at temperature lower than 40 degrees C being stabilized by hydrogen bonds in which N(7) atoms of guanylic residues take part.", "contents": "[Reaction capabilities and structure of poly(rG) and poly(rG)-poly(rC) in solution by the method of the kinetics of hydrogen ion exchange]. Data on the kinetics of 1H greater than 3H exchange between water and C(8)H groups of guanylic residues in the poly(rG) and poly poly(rG)-poly(rC) are presented. Furthermore, optical properties (CD spectra and hyperchromism) of neutral solutions of these polymers from 20 to 100 degrees C are described. It is shown that the exchange in poly(rG) within the temperature range from 20 to 80 degrees C proceeds faster than in rGMP. Within the temperature range from 20 to 40 degrees C such an acceleration of the exchange is observed also in poly(rG)-poly(rC). According to the ylide mechanism of the exchange reaction the observed accleration of the exchanged in in C(8)H groups of guanylic residues is considered as a consequence of an increase of the positive charge at N(7) atoms. This effect is due to formation of additional hydrogen bonds in which N(7) atoms take part. The exchange in poly(rG)-poly(rG) at temperatures hihger than 75 degrees C, when these additional hydrogen bonds are absent, proceeds more slowly than in rGMP. Such picture is usual in other previously studied polynucleotides whose structure in solution is stabilized only by Watson - Crick hydrogen bonds and stacking interactions. The data obtained support a Guschelbauer's model of the four-stranded stranded poly(rG). They also indicate the posibility of associates formation in poly(rG)-poly(rC) solutions at temperature lower than 40 degrees C being stabilized by hydrogen bonds in which N(7) atoms of guanylic residues take part."} {"id": "PMID:183103", "title": "[Determination of the distance between spin labels and the paramagnetic center in spin-labeled proteins according to parameters of the saturation curves of the label EPR spectra at 77 degrees K].", "content": "A new method of estimation of the distance between spins of the spin-label and paramagnetic center is suggested. Method is based on the quantitative analys of saturation curve of spin-label EPR spectra at 77 degrees K. New approaches have been tested using haemoglobin labeled on SH-groups with various iminoxyl radicals. Values of the distances between labels and haem estimated from the saturation curve parameters and by current methods and values of distances estimated from X-ray data are in good agreement. In the case of rapid spin relaxation of he paramagnetic center, the new method allows one to determine a farther distance. Results of the present work make it possible to investigat by the spin-label technique the structure of haem-containing propeins and the structure of other proteins with known spin relaxation time of paramagnetic center.", "contents": "[Determination of the distance between spin labels and the paramagnetic center in spin-labeled proteins according to parameters of the saturation curves of the label EPR spectra at 77 degrees K]. A new method of estimation of the distance between spins of the spin-label and paramagnetic center is suggested. Method is based on the quantitative analys of saturation curve of spin-label EPR spectra at 77 degrees K. New approaches have been tested using haemoglobin labeled on SH-groups with various iminoxyl radicals. Values of the distances between labels and haem estimated from the saturation curve parameters and by current methods and values of distances estimated from X-ray data are in good agreement. In the case of rapid spin relaxation of he paramagnetic center, the new method allows one to determine a farther distance. Results of the present work make it possible to investigat by the spin-label technique the structure of haem-containing propeins and the structure of other proteins with known spin relaxation time of paramagnetic center."} {"id": "PMID:183108", "title": "Radiation enhanced reactivation of herpes simplex virus: effect of caffeine.", "content": "Ultaviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since cafeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation.", "contents": "Radiation enhanced reactivation of herpes simplex virus: effect of caffeine. Ultaviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since cafeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation."} {"id": "PMID:183104", "title": "[Kinetic manifestations of the interaction of active centers in swine skeletal muscle D-glyceraldehyde-3-phosphate dehydrogenase].", "content": "The kinetic method and selective chemical modification have been used in studies of the kinetic manifestations of active site interactions in D-glyceraldehyde-3-phosphate dehydrogenase (GAP dehydrogenase). The reactions of glyceraldehyde and glyceraldehyde-3-phosphate oxidation were studied in the absence of substrate excess. In support of the data obtained previously it was shown that only a part of the tightly bound NAD molecules can be reduced after substrate addition. \"Partial reducibility\" is observed at various degrees of saturation of the enzyme with NAD involving a single NAD molecule per tetrametric enzyme. These facts can hardly be explained by assumption of functional non-equivalence of active sites, whether induced by coenzyme or preexisting in the apoenzyme. It was proven by selective alkylation of the catalytic SH groups that \"partial reducibility\" is due to the circumstance that equilibrium in the system under investigation is established at nearly equal NAD and NADH concentrations. A plot of initial reaction rates versus NAD concentration (at non-saturating substrate concentrations) gives S-shaped curves; this is explained by considerable enzyme activation upon saturation of the fourth site with coenzyme. After modification of three active sites with iodoacetate the S-shape of the curve disappeared. This fact leads to the conclusion that active site interactions are required for formation of the S-shaped curves. The activity of a single site functioning in the modified enzyme reached values equal to those of the active sites in the native enzyme in the fully activated state. A model is proposed which can explaine the variations in mode of enzyme activation in the native and modified states. It is suggested that the surroundings of all four SH groups must be altered in order to activate the enzyme; such changes can be induced either by alkylation of the SH groups or by NAD binding. Evidence is presented that important functional properties of GAP dehydrogenase cannot be elucidated at low enzyme concentrations and with excess of substrates: three active sites are saturated under such conditons and practically inactive, and the fourth site obeys Michaelis - Menten kinetics.", "contents": "[Kinetic manifestations of the interaction of active centers in swine skeletal muscle D-glyceraldehyde-3-phosphate dehydrogenase]. The kinetic method and selective chemical modification have been used in studies of the kinetic manifestations of active site interactions in D-glyceraldehyde-3-phosphate dehydrogenase (GAP dehydrogenase). The reactions of glyceraldehyde and glyceraldehyde-3-phosphate oxidation were studied in the absence of substrate excess. In support of the data obtained previously it was shown that only a part of the tightly bound NAD molecules can be reduced after substrate addition. \"Partial reducibility\" is observed at various degrees of saturation of the enzyme with NAD involving a single NAD molecule per tetrametric enzyme. These facts can hardly be explained by assumption of functional non-equivalence of active sites, whether induced by coenzyme or preexisting in the apoenzyme. It was proven by selective alkylation of the catalytic SH groups that \"partial reducibility\" is due to the circumstance that equilibrium in the system under investigation is established at nearly equal NAD and NADH concentrations. A plot of initial reaction rates versus NAD concentration (at non-saturating substrate concentrations) gives S-shaped curves; this is explained by considerable enzyme activation upon saturation of the fourth site with coenzyme. After modification of three active sites with iodoacetate the S-shape of the curve disappeared. This fact leads to the conclusion that active site interactions are required for formation of the S-shaped curves. The activity of a single site functioning in the modified enzyme reached values equal to those of the active sites in the native enzyme in the fully activated state. A model is proposed which can explaine the variations in mode of enzyme activation in the native and modified states. It is suggested that the surroundings of all four SH groups must be altered in order to activate the enzyme; such changes can be induced either by alkylation of the SH groups or by NAD binding. Evidence is presented that important functional properties of GAP dehydrogenase cannot be elucidated at low enzyme concentrations and with excess of substrates: three active sites are saturated under such conditons and practically inactive, and the fourth site obeys Michaelis - Menten kinetics."} {"id": "PMID:183109", "title": "Infection of UV-irradiated xeroderma pigmentosum fibroblasts by herpes simplex virus: study of capacity and Weigle reactivation.", "content": "The capacity of monolayers of both normal human and xeroderma pigmentosum (XP) filbroblasts to support plaque formation by herpes simplex virus was decreased when the monolayers were ultraviolet (UV) irradiated and infected with virus. Fibroblasts of XP complementation groups A, B, and D were sensitive to UV, being 4-6 fold more sensitive than either fibroblasts of XP complementation group C or fibroblasts from a normal individual. When the monolayers were irradiated 4 days prior to infection, the capacity of normal fibroblasts to support herpes virus growth recovered, whereas the capacity of the XP strains decreased further compared to that measured when infection immediately followed irradiation. Concurrent experiments with UV-irradiated herpes virus showed that the survival of this virus did not increase when infection by irradiated virus immediately followed irradiation of the monolayers. However, if the monolayers were irradiated 4 days prior to infection, the survival of this virus increased by a factor of nearly 2. Such Weigle reactivation (WR) occurred at lower fluences to the XP fibroblasts than to normal fibroblasts, suggesting that WR results from residual cellular DNA damage left after excision repair.", "contents": "Infection of UV-irradiated xeroderma pigmentosum fibroblasts by herpes simplex virus: study of capacity and Weigle reactivation. The capacity of monolayers of both normal human and xeroderma pigmentosum (XP) filbroblasts to support plaque formation by herpes simplex virus was decreased when the monolayers were ultraviolet (UV) irradiated and infected with virus. Fibroblasts of XP complementation groups A, B, and D were sensitive to UV, being 4-6 fold more sensitive than either fibroblasts of XP complementation group C or fibroblasts from a normal individual. When the monolayers were irradiated 4 days prior to infection, the capacity of normal fibroblasts to support herpes virus growth recovered, whereas the capacity of the XP strains decreased further compared to that measured when infection immediately followed irradiation. Concurrent experiments with UV-irradiated herpes virus showed that the survival of this virus did not increase when infection by irradiated virus immediately followed irradiation of the monolayers. However, if the monolayers were irradiated 4 days prior to infection, the survival of this virus increased by a factor of nearly 2. Such Weigle reactivation (WR) occurred at lower fluences to the XP fibroblasts than to normal fibroblasts, suggesting that WR results from residual cellular DNA damage left after excision repair."} {"id": "PMID:183105", "title": "Differential cytology in the diagnosis of astrocytary gliomas. A statistical study using the \"t\" Students-Fisher test.", "content": "The authors have used the \"t\" Student-Fisher test in order to verify the differences between two compared average values. The results show the anatomo-clinical individuality of four main types of astrocytary gliomas; multiform glioblastoma, malignant astrocytoma, protoplasmatic astrocytoma, and fibrillary astrocytoma. The occurrence of significant quantitative differences between these four astrocytary gliomas indicates that the histological diagnosis must be differentially made, because these astrocytary neoplasias represent individualized anatomo-clinical entities.", "contents": "Differential cytology in the diagnosis of astrocytary gliomas. A statistical study using the \"t\" Students-Fisher test. The authors have used the \"t\" Student-Fisher test in order to verify the differences between two compared average values. The results show the anatomo-clinical individuality of four main types of astrocytary gliomas; multiform glioblastoma, malignant astrocytoma, protoplasmatic astrocytoma, and fibrillary astrocytoma. The occurrence of significant quantitative differences between these four astrocytary gliomas indicates that the histological diagnosis must be differentially made, because these astrocytary neoplasias represent individualized anatomo-clinical entities."} {"id": "PMID:183110", "title": "Inactivation and mutation of coliphage T4 by aliphatic nitrosamides and methanesulphonates: in vitro recovery of infectivity of T4 inactivated by isopropyl methanesulphonate.", "content": "The inactivation and mutation (to r phenotype) of extracellular coliphage T4 wild-type by the monofunctional alkylating agents N-methyl- and N-ethyl-N-nitrosourea and isopropyl methanesulphonate were investigated. The rate and extent of change in phage infectivity observed during the post-treatment period were found to correlate with what is known of the mechanisms by which these agents react in vitro. Loss of phage infectivity was found to occur during the period following treatment with these agents, but that resulting from treatment with isopropyl methanesulphonate was preceded, in the first 24 to 48 h, by a recovery of infectivity. This suggested that changes in phage infectivity occurring after treatment with monofunctional alkylating agents are resultant of various processes which diversely promote loss and recovery of infectivity. The mutagenicity of N-methyl-N-nitrosourea was similar to that of its ethyl homologue at a level of phage survival of 4 x 10-3, but less than that of isopropyl methanesulphonate. At a level of survival of 3 x 10-2 ethyl methanesulphonate was a mutagenic as its isopropyl homologue, but methyl methanesulphonate was only slightly if at all mutagenic. These results could not be correlated with the compounds' reaction mechanisms. The efficiency of isopropyl methanesulphonate (compared with its toxicity to phage) was found to decrease as the severity of the dose was increased.", "contents": "Inactivation and mutation of coliphage T4 by aliphatic nitrosamides and methanesulphonates: in vitro recovery of infectivity of T4 inactivated by isopropyl methanesulphonate. The inactivation and mutation (to r phenotype) of extracellular coliphage T4 wild-type by the monofunctional alkylating agents N-methyl- and N-ethyl-N-nitrosourea and isopropyl methanesulphonate were investigated. The rate and extent of change in phage infectivity observed during the post-treatment period were found to correlate with what is known of the mechanisms by which these agents react in vitro. Loss of phage infectivity was found to occur during the period following treatment with these agents, but that resulting from treatment with isopropyl methanesulphonate was preceded, in the first 24 to 48 h, by a recovery of infectivity. This suggested that changes in phage infectivity occurring after treatment with monofunctional alkylating agents are resultant of various processes which diversely promote loss and recovery of infectivity. The mutagenicity of N-methyl-N-nitrosourea was similar to that of its ethyl homologue at a level of phage survival of 4 x 10-3, but less than that of isopropyl methanesulphonate. At a level of survival of 3 x 10-2 ethyl methanesulphonate was a mutagenic as its isopropyl homologue, but methyl methanesulphonate was only slightly if at all mutagenic. These results could not be correlated with the compounds' reaction mechanisms. The efficiency of isopropyl methanesulphonate (compared with its toxicity to phage) was found to decrease as the severity of the dose was increased."} {"id": "PMID:183111", "title": "Mutagenic and inactivating effects of methyl alkylaminosulfonates on Escherichia coli.", "content": "Methyl alkylamino methanesulfonates are mutagenic agents as shown by treating several strains of E. coli at pH 7. Methyl methylaminosulfonate (CH3-NH-SO3-CH3) was more efficient than methyl ethylaminosulfonate (C2H5-NH-SO3-CH3) which itself was more efficient than methyl isopropylaminosulfonate (C3H7-NH-SO3-CH3). Methyl methylaminosulfonate seemed to be at least as effective as methyl methanesulfonate (CH3-SO3-CH3). Methyl methylaminosulfonate produced a yield of up to 1% of auxotrophic mutants. All three new mutagens appeared to react according to the same mechanism by ester fission and methylation of nucleophilic groups as is known for methyl methanesulfonate. The reaction mechanism seems to be of the SN2 type.", "contents": "Mutagenic and inactivating effects of methyl alkylaminosulfonates on Escherichia coli. Methyl alkylamino methanesulfonates are mutagenic agents as shown by treating several strains of E. coli at pH 7. Methyl methylaminosulfonate (CH3-NH-SO3-CH3) was more efficient than methyl ethylaminosulfonate (C2H5-NH-SO3-CH3) which itself was more efficient than methyl isopropylaminosulfonate (C3H7-NH-SO3-CH3). Methyl methylaminosulfonate seemed to be at least as effective as methyl methanesulfonate (CH3-SO3-CH3). Methyl methylaminosulfonate produced a yield of up to 1% of auxotrophic mutants. All three new mutagens appeared to react according to the same mechanism by ester fission and methylation of nucleophilic groups as is known for methyl methanesulfonate. The reaction mechanism seems to be of the SN2 type."} {"id": "PMID:183107", "title": "Relationships between the changes of some oxidative and hydrolytic enzymes in the kidney of irradiated rat.", "content": "Changes of succinic dehydrogenase, adenosinetriphosphatase, alkaline and acid phosphatase in rat kidney, during 6 months after a whole-body 800 r X-ray exposure were studied. Temporary but long-lasting activation of the histoenzymatic reactions accompanied by partly reversible diffusion of enzymes related to the dystrophic and restoring postirradiation renal changes were observed.", "contents": "Relationships between the changes of some oxidative and hydrolytic enzymes in the kidney of irradiated rat. Changes of succinic dehydrogenase, adenosinetriphosphatase, alkaline and acid phosphatase in rat kidney, during 6 months after a whole-body 800 r X-ray exposure were studied. Temporary but long-lasting activation of the histoenzymatic reactions accompanied by partly reversible diffusion of enzymes related to the dystrophic and restoring postirradiation renal changes were observed."} {"id": "PMID:183112", "title": "Non-endemic Burkitts's lymphoma. A B-cell tumor related to germinal centers.", "content": "To investigate the nature of non-endemic Burkitt's lymphoma, we examined neoplastic cells from eight American patients for receptors for sheep erythrocytes (E), complement (EAC), and Fc fragment of lgG (igGEA), and for surface immunoglobulins (Slg) and hydrolytic enzymes. In addition, we reviewed 47 biopsies and 17 autopsies from American patients to ascertain patterns of involvement by tumor in lymph nodes, spleens and Peyer's patches. Neoplastic cells in all cases studies bore monoclonal surface immunoglobulins of the igM class. Receptors for EAC and igGEA were identified on a minority of the cells. Little or no hydrolytic enzyme activity was demonstrable. These results indicate that, like Burkitt's lymphoma in Africans, this histologically identical tumor in American patients consists of B lymphocytes. In 10 biopsies and two autopsies, germinal centers were selectively involved by tumor, suggesting that these neoplastic cells may be related to some B lymphocytes of normal germinal centers.", "contents": "Non-endemic Burkitts's lymphoma. A B-cell tumor related to germinal centers. To investigate the nature of non-endemic Burkitt's lymphoma, we examined neoplastic cells from eight American patients for receptors for sheep erythrocytes (E), complement (EAC), and Fc fragment of lgG (igGEA), and for surface immunoglobulins (Slg) and hydrolytic enzymes. In addition, we reviewed 47 biopsies and 17 autopsies from American patients to ascertain patterns of involvement by tumor in lymph nodes, spleens and Peyer's patches. Neoplastic cells in all cases studies bore monoclonal surface immunoglobulins of the igM class. Receptors for EAC and igGEA were identified on a minority of the cells. Little or no hydrolytic enzyme activity was demonstrable. These results indicate that, like Burkitt's lymphoma in Africans, this histologically identical tumor in American patients consists of B lymphocytes. In 10 biopsies and two autopsies, germinal centers were selectively involved by tumor, suggesting that these neoplastic cells may be related to some B lymphocytes of normal germinal centers."} {"id": "PMID:183113", "title": "Distribution of antibody to hepatitis a antigen in urban adult populations.", "content": "To investigate the prevalence and distribution of antibody to hepatitis A antigen we tested 947 randomly selected people in the Greater New York City area; 45 per cent were antigen positive, as determined by the immune adherence method. Antibody was detected two to three times more frequently in lower social classes (72 to 80 per cent) than in middle and upper-middle classes (18 to 30 per cent). The rate of antibody detection was strongly correlated with age; the prevalence gradually increased throughout adulthood and reached its peak level in people 50 years of age and older. Those with serologic evidence of past exposure to hepatitis B virus were significantly more often antibody positive than those without such evidence (61 vs. 40 per cent; P less than 0.001). Very few of the positive subjects had had hepatitis. The prevalence of this antibody varies among different population groups, increases with age, decreases with rise in socioeconomic status, is independent on sex and race, and correlates with serologic evidence of hepatitis B virus infections.", "contents": "Distribution of antibody to hepatitis a antigen in urban adult populations. To investigate the prevalence and distribution of antibody to hepatitis A antigen we tested 947 randomly selected people in the Greater New York City area; 45 per cent were antigen positive, as determined by the immune adherence method. Antibody was detected two to three times more frequently in lower social classes (72 to 80 per cent) than in middle and upper-middle classes (18 to 30 per cent). The rate of antibody detection was strongly correlated with age; the prevalence gradually increased throughout adulthood and reached its peak level in people 50 years of age and older. Those with serologic evidence of past exposure to hepatitis B virus were significantly more often antibody positive than those without such evidence (61 vs. 40 per cent; P less than 0.001). Very few of the positive subjects had had hepatitis. The prevalence of this antibody varies among different population groups, increases with age, decreases with rise in socioeconomic status, is independent on sex and race, and correlates with serologic evidence of hepatitis B virus infections."} {"id": "PMID:183150", "title": "A possible common mechanism of action of antidepressant treatments: reduction in the sensitivity of the noradrenergic cyclic AMP gererating system in the rat limbic forebrain.", "content": "The response of the noNEpinephrine (NE) sensitive cyclic AMP generating system in slices of the rat limbic forebrain after both the acute and chronic administration of the tricyclic antidepressants desipramine (DMI) and iprindole as well as electro-convulsive treatment (ECT) was investigated. Neither the basal level of cyclic AMP nor the hormonal response to NE were altered after administration of a single dose of short term treatment with DMI and iprindole. However, the administration of the antidepressants on a clinically more relevant time basis markedly reduced the sensitivity of the cyclic AMP generating system to NE. This change in sensitivity was not related to the levels of the drugs in brain. The response of cyclic AMP to NE was also reduced by ECT, but the onset of this action was shorter than that observed with the antidepressants. ECT also antagonized the enhanced response of cyclic AMP to NE following destruction of central adrenergic nerve terminals with 6-hydroxydopamine. It thus appears that the therapeutic action of tricyclic antidepressants could be related to postsynaptic adaptive changes in the sensitivity of the noradrenergic adenylate cyclase receptor system rather than to acute presynaptic events.", "contents": "A possible common mechanism of action of antidepressant treatments: reduction in the sensitivity of the noradrenergic cyclic AMP gererating system in the rat limbic forebrain. The response of the noNEpinephrine (NE) sensitive cyclic AMP generating system in slices of the rat limbic forebrain after both the acute and chronic administration of the tricyclic antidepressants desipramine (DMI) and iprindole as well as electro-convulsive treatment (ECT) was investigated. Neither the basal level of cyclic AMP nor the hormonal response to NE were altered after administration of a single dose of short term treatment with DMI and iprindole. However, the administration of the antidepressants on a clinically more relevant time basis markedly reduced the sensitivity of the cyclic AMP generating system to NE. This change in sensitivity was not related to the levels of the drugs in brain. The response of cyclic AMP to NE was also reduced by ECT, but the onset of this action was shorter than that observed with the antidepressants. ECT also antagonized the enhanced response of cyclic AMP to NE following destruction of central adrenergic nerve terminals with 6-hydroxydopamine. It thus appears that the therapeutic action of tricyclic antidepressants could be related to postsynaptic adaptive changes in the sensitivity of the noradrenergic adenylate cyclase receptor system rather than to acute presynaptic events."} {"id": "PMID:183151", "title": "Possible role of cyclic AMP in the relaxation process of mammalian heart: effects of dibutyryl cyclic AMP and theophylline on potassium contractures in cat papillary muscles.", "content": "The effect of dibutyryl cyclic AMP (DB-c-AMP; 3 X 10(-4)-3 X 10(-3) M) on electrically induced twitch and high potassium (142.4 mM KCl)-induced contracture tension was studied in papillary muscles from normal and reserpinized cats ([Ca]0 1.8 mM; 25 degrees C; pH 7.4). In both groups of preparations, the increase in twitch tension evoked by DB-c-AMP was accompanied by an abbreviation of the time to peak force and of relaxation time. In the same preparations, the high potassium contracture was markedly depressed by DB-c-AMP in a concentration-dependent manner. Similar results were obtained with the N6-monobutyryl derivative of cyclic AMP. The relaxing effects of the cyclic nucleotides on KCl contractures did not appear to be due to possible non-cyclic breakdown products: adenosine, 5'-AMP and sodium butyrate did not attenuate contracture tension at concentrations up to 3 X 10(-3) M. The same applies to ATP and non-cyclic N6-2'-0-3'-0-tributyryl-adenosine-monophosphate. Theophylline (10(-2) M) was found to prolong the relaxation time of the twitch and to enhance the high KCl contracture. It is concluded that cyclic AMP may be capable of modulating the relaxation process of mammalian heart and that not only the positive inotropic but also the relaxant effects of catecholamines on myocardium described before may be mediated by the cyclic AMP system. The relaxant effects of cyclic AMP derivatives on intact myocardial preparations are attributed to a stimulation by cyclic AMP of the calcium transport of the sarcoplasmic reticulum (SR) and are interpreted to be a corollary to the effects of cyclic AMP previously obtained on isolated SR preparations.", "contents": "Possible role of cyclic AMP in the relaxation process of mammalian heart: effects of dibutyryl cyclic AMP and theophylline on potassium contractures in cat papillary muscles. The effect of dibutyryl cyclic AMP (DB-c-AMP; 3 X 10(-4)-3 X 10(-3) M) on electrically induced twitch and high potassium (142.4 mM KCl)-induced contracture tension was studied in papillary muscles from normal and reserpinized cats ([Ca]0 1.8 mM; 25 degrees C; pH 7.4). In both groups of preparations, the increase in twitch tension evoked by DB-c-AMP was accompanied by an abbreviation of the time to peak force and of relaxation time. In the same preparations, the high potassium contracture was markedly depressed by DB-c-AMP in a concentration-dependent manner. Similar results were obtained with the N6-monobutyryl derivative of cyclic AMP. The relaxing effects of the cyclic nucleotides on KCl contractures did not appear to be due to possible non-cyclic breakdown products: adenosine, 5'-AMP and sodium butyrate did not attenuate contracture tension at concentrations up to 3 X 10(-3) M. The same applies to ATP and non-cyclic N6-2'-0-3'-0-tributyryl-adenosine-monophosphate. Theophylline (10(-2) M) was found to prolong the relaxation time of the twitch and to enhance the high KCl contracture. It is concluded that cyclic AMP may be capable of modulating the relaxation process of mammalian heart and that not only the positive inotropic but also the relaxant effects of catecholamines on myocardium described before may be mediated by the cyclic AMP system. The relaxant effects of cyclic AMP derivatives on intact myocardial preparations are attributed to a stimulation by cyclic AMP of the calcium transport of the sarcoplasmic reticulum (SR) and are interpreted to be a corollary to the effects of cyclic AMP previously obtained on isolated SR preparations."} {"id": "PMID:183152", "title": "Antagonistic effects against single lethal doses of Amanita phalloides.", "content": "Agents with antagonistic effects against phalloidin or alpha-amanitin were tested in mice against lethal doses of an extract from the whole mushroom Amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) anti-phallotoxic acitivty. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against alpha-amanitin did not reduce the lethality of the exact. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular couse which is difficult to ascribe to phallo- or amatoxic effects alone.", "contents": "Antagonistic effects against single lethal doses of Amanita phalloides. Agents with antagonistic effects against phalloidin or alpha-amanitin were tested in mice against lethal doses of an extract from the whole mushroom Amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) anti-phallotoxic acitivty. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against alpha-amanitin did not reduce the lethality of the exact. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular couse which is difficult to ascribe to phallo- or amatoxic effects alone."} {"id": "PMID:183153", "title": "Inhibition by polyhalogenated hydrocarbons (PHHC) of ATPases in plasma membranes of parenchymal liver cells.", "content": "Suspensions of freshly prepared plasma membranes from rat livers were equilibrated with defined mixtures of air with polyhalogenated hydro-carbons (PHHC) at 37 degrees C. During the exposition enzymatic degradation of ATP was inhibited by carbon tetrachloride, chloroform and halothane in a dose-dependent manner. On a molar basis carbon tetrachloride was 5 times more effective than chloroform and halothane. The inhibition was partially reversible. Diethyldithiocarbamate, an agent protecting animals against carbon tetrachloride, was ineffective in this assay.", "contents": "Inhibition by polyhalogenated hydrocarbons (PHHC) of ATPases in plasma membranes of parenchymal liver cells. Suspensions of freshly prepared plasma membranes from rat livers were equilibrated with defined mixtures of air with polyhalogenated hydro-carbons (PHHC) at 37 degrees C. During the exposition enzymatic degradation of ATP was inhibited by carbon tetrachloride, chloroform and halothane in a dose-dependent manner. On a molar basis carbon tetrachloride was 5 times more effective than chloroform and halothane. The inhibition was partially reversible. Diethyldithiocarbamate, an agent protecting animals against carbon tetrachloride, was ineffective in this assay."} {"id": "PMID:183154", "title": "Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement.", "content": "The action of adenosine on adrenergic neuroeffector transmission was studied in the rabbit kidney in vitro and in situ, in the canine subcutaneous adipose tissue in situ and in the guinea pig vas deferens in vitro. In the kidney, adenosine (0.1-10 muM) caused a concentration-dependent increase in vascular resistance and in vasoconstrictor responses to nerve stimulation and administered noradrenaline. In the adipose tissue, adenosine also increased the vaso-constrictor responses but it decreased vascular resistance. In all three tissues studied adenosine significantly and reversibly depressed noradrenaline release evoked by nerve stimulation in a concentration-dependent manner. This effect of adenosine was not altered by phenoxybenzamine which blocked all vasoconstrictor responses and diminished the rise in vascular resistance by adenosine in the kidney. It is concluded that adenosine affects adrenergic neuroeffector transmission by two discrete mechanisms, prejunctional inhibition and postjunctional enhancement.", "contents": "Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. The action of adenosine on adrenergic neuroeffector transmission was studied in the rabbit kidney in vitro and in situ, in the canine subcutaneous adipose tissue in situ and in the guinea pig vas deferens in vitro. In the kidney, adenosine (0.1-10 muM) caused a concentration-dependent increase in vascular resistance and in vasoconstrictor responses to nerve stimulation and administered noradrenaline. In the adipose tissue, adenosine also increased the vaso-constrictor responses but it decreased vascular resistance. In all three tissues studied adenosine significantly and reversibly depressed noradrenaline release evoked by nerve stimulation in a concentration-dependent manner. This effect of adenosine was not altered by phenoxybenzamine which blocked all vasoconstrictor responses and diminished the rise in vascular resistance by adenosine in the kidney. It is concluded that adenosine affects adrenergic neuroeffector transmission by two discrete mechanisms, prejunctional inhibition and postjunctional enhancement."} {"id": "PMID:183156", "title": "Immunodiffusion analysis of the antigenic structure of the transplantable MC 29 tumor.", "content": "By the use of specific anti-chicken liver sera it could be proved with immunodiffusion techniques that the transplantable MC 29 tumor line contains liver-specific antigens. Production of chicken serum-proteins by the tumor could also be demonstrated. Thus, the transplantable MC 29 tumor line can be regarded as a hepatoma.", "contents": "Immunodiffusion analysis of the antigenic structure of the transplantable MC 29 tumor. By the use of specific anti-chicken liver sera it could be proved with immunodiffusion techniques that the transplantable MC 29 tumor line contains liver-specific antigens. Production of chicken serum-proteins by the tumor could also be demonstrated. Thus, the transplantable MC 29 tumor line can be regarded as a hepatoma."} {"id": "PMID:183155", "title": "Differentiation of intestinal smooth muscle relaxation caused by drugs that inhibit phosphodiesterase.", "content": "In this study a number of chemically unrelated smooth muscle relaxants were tested: a) for potency of phosphodiesterase (PDE)-inhibition, using guinea pig colon-PDE and rat erythrocyte-PDE, b) for potency and duration of relaxation of the isolated guinea-pig colon, c) for their interaction with NH4Cl and orciprenaline as well as with \"high calcium\". Compared with the spasmolytic effect inhibition of guinea pig colon-PDE or rat erythrocyte-PDE was strong for papaverine and some other relaxants but was low or virtually absent with verapamil, hexobendine and bencyclane. The spasmolytic effect of some PDE-inhibitors was found diminished by the PDE-activator NH4Cl. Most of these drugs enhanced the relaxant effect of the \"cyclase activator\" orciprenaline; the latter are designated A-type drugs. Verapamil, bencyclane, hexobendine and M 13 did not show this type of interaction with NH4Cl and orciprenaline; they are designated B-type drugs. With A-type drugs--but not with B-type drugs--a highly significant correlation was observed between potency of relaxation and inhibition of colon-PDE (r = 0.85) as well as rat erythrocyte-PDE (r = 0.77). The spasmolytic action of aminophylline and papaverine (A-type drugs) was not inhibited by elevation of extracellular calcium to 9 mM, whereas relaxation induced by verapamil and hexobendine (B-type drugs) at 1.8 mM calcium was found abolished by 9 mM calcium. It is concluded that A-type drugs relax guinea-pig colon by inhibition of PDE and accumulation of cAMP, and that B-type drugs in all probability act by (a) cAMP-independent mechanism(s).", "contents": "Differentiation of intestinal smooth muscle relaxation caused by drugs that inhibit phosphodiesterase. In this study a number of chemically unrelated smooth muscle relaxants were tested: a) for potency of phosphodiesterase (PDE)-inhibition, using guinea pig colon-PDE and rat erythrocyte-PDE, b) for potency and duration of relaxation of the isolated guinea-pig colon, c) for their interaction with NH4Cl and orciprenaline as well as with \"high calcium\". Compared with the spasmolytic effect inhibition of guinea pig colon-PDE or rat erythrocyte-PDE was strong for papaverine and some other relaxants but was low or virtually absent with verapamil, hexobendine and bencyclane. The spasmolytic effect of some PDE-inhibitors was found diminished by the PDE-activator NH4Cl. Most of these drugs enhanced the relaxant effect of the \"cyclase activator\" orciprenaline; the latter are designated A-type drugs. Verapamil, bencyclane, hexobendine and M 13 did not show this type of interaction with NH4Cl and orciprenaline; they are designated B-type drugs. With A-type drugs--but not with B-type drugs--a highly significant correlation was observed between potency of relaxation and inhibition of colon-PDE (r = 0.85) as well as rat erythrocyte-PDE (r = 0.77). The spasmolytic action of aminophylline and papaverine (A-type drugs) was not inhibited by elevation of extracellular calcium to 9 mM, whereas relaxation induced by verapamil and hexobendine (B-type drugs) at 1.8 mM calcium was found abolished by 9 mM calcium. It is concluded that A-type drugs relax guinea-pig colon by inhibition of PDE and accumulation of cAMP, and that B-type drugs in all probability act by (a) cAMP-independent mechanism(s)."} {"id": "PMID:183157", "title": "Transplantability and biological behavior of a rapidly growing secondary Morris hepatoma.", "content": "Transplantable hepatomas have a special importance in cancer research because most are well-differentiated and grow at widely differing rates. A simple and reproducible technique was developed to transplant the rapidly growing Morris hepatoma 9618A2 from a subcutaneous to an intrahepatic site. The tumor has been maintained for over 80 successive transplant generations by inoculating Buffalo rats subcutaneously. The hepatoma, transplanted many times from the subcutaneous site to the liver, was examined histologically on various occasions. By varying inoculum size, growth of the hepatocarcinoma could be controlled. Throughout transplantation, the donor animals were bled without causing the death of the animal. Histological studies revealed that the tumor, when transplanted intrahepatically, remains a highly differentiated neoplasm with no observable morphological changes.", "contents": "Transplantability and biological behavior of a rapidly growing secondary Morris hepatoma. Transplantable hepatomas have a special importance in cancer research because most are well-differentiated and grow at widely differing rates. A simple and reproducible technique was developed to transplant the rapidly growing Morris hepatoma 9618A2 from a subcutaneous to an intrahepatic site. The tumor has been maintained for over 80 successive transplant generations by inoculating Buffalo rats subcutaneously. The hepatoma, transplanted many times from the subcutaneous site to the liver, was examined histologically on various occasions. By varying inoculum size, growth of the hepatocarcinoma could be controlled. Throughout transplantation, the donor animals were bled without causing the death of the animal. Histological studies revealed that the tumor, when transplanted intrahepatically, remains a highly differentiated neoplasm with no observable morphological changes."} {"id": "PMID:183164", "title": "Adrenocortical responses of rats to acute hypoxic and hypercapnic stresses after treatment with aminergic agents.", "content": "Monoaminergic influences on the regulation of the hypothalamo-hypophyseal-adrenocortical (HHA) system during acute stresses (hypoxia and hypercapnia) were investigated in male rats. Plasma corticosterone levels were used to assess HHA activity, and the alterations in monoaminergic activity were induced by pretreating the animals with various pharmacologic agents (reserpine, alpha MT, FLA-63, pCPA, L-Dopa, pargyline, Lilly 110140, phentolamine and propranolol). Dexamethasone-treated rats were utilized to assess the site at which these monoaminergic substances acted. The latter experiments showed that these agents did not have a marked effect directly on the adrenal cortex and thus the site(s) of action was at the level of the anterior pituitary and/or above. Altering the serotoninergic system did not appreciably influence the HHA response to hypoxia and hypercapnia, whereas increasing the activity of the adrenergic system partially prevented the rise usually observed in plasma corticosterone levels during these stresses. These data suggest that different aminergic pathways may be utilized for different stresses.", "contents": "Adrenocortical responses of rats to acute hypoxic and hypercapnic stresses after treatment with aminergic agents. Monoaminergic influences on the regulation of the hypothalamo-hypophyseal-adrenocortical (HHA) system during acute stresses (hypoxia and hypercapnia) were investigated in male rats. Plasma corticosterone levels were used to assess HHA activity, and the alterations in monoaminergic activity were induced by pretreating the animals with various pharmacologic agents (reserpine, alpha MT, FLA-63, pCPA, L-Dopa, pargyline, Lilly 110140, phentolamine and propranolol). Dexamethasone-treated rats were utilized to assess the site at which these monoaminergic substances acted. The latter experiments showed that these agents did not have a marked effect directly on the adrenal cortex and thus the site(s) of action was at the level of the anterior pituitary and/or above. Altering the serotoninergic system did not appreciably influence the HHA response to hypoxia and hypercapnia, whereas increasing the activity of the adrenergic system partially prevented the rise usually observed in plasma corticosterone levels during these stresses. These data suggest that different aminergic pathways may be utilized for different stresses."} {"id": "PMID:183165", "title": "Injection of melatonin into cisterna magna increases concentration of 3', 5' cyclic guanosine monophosphate in cerebrospinal fluid.", "content": "Rabbits were anesthetized with urethane and were given intracisternal injections of the following substances: adrenocorticotropin, beta-melanocyte stimulating hormone, choroid plexus peptide IIF, epinephrine, serotonin, histamine, oxytocin, lysine and a arginine vasopressins, acetylcholine and melatonin. The effects on the concentration of 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid were then measured. Only melatonin and acetylcholine caused a significant (p less than 0.05) effect on cGMP concentration. Both agents increased the nucleotide's concentration within 30 min. Melatonin was about 1,000 times more potent than acetylcholine; the mininal effective doses were 1 mug and 1,000 mug, respectively.", "contents": "Injection of melatonin into cisterna magna increases concentration of 3', 5' cyclic guanosine monophosphate in cerebrospinal fluid. Rabbits were anesthetized with urethane and were given intracisternal injections of the following substances: adrenocorticotropin, beta-melanocyte stimulating hormone, choroid plexus peptide IIF, epinephrine, serotonin, histamine, oxytocin, lysine and a arginine vasopressins, acetylcholine and melatonin. The effects on the concentration of 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid were then measured. Only melatonin and acetylcholine caused a significant (p less than 0.05) effect on cGMP concentration. Both agents increased the nucleotide's concentration within 30 min. Melatonin was about 1,000 times more potent than acetylcholine; the mininal effective doses were 1 mug and 1,000 mug, respectively."} {"id": "PMID:183162", "title": "[Serum lipids in Down's syndrome].", "content": "In 28 patients with Down syndrome and in 28 controls matched for age and sex serum lipoproteins and their main lipid constituents were determined. Both groups comprised subjects living in the same institutions for mentally retarded No significant differences were found between the two groups in total serum lipids, triglycerides, total cholesterol and phospholipid levels and in the proportion of esterified cholesterol and beta-lipoproteins. No characteristic pattern of alpha and beta lipoproteins could be observed in patients with Down syndrome by means of electrophoresis in polyacrylamide gel. Alanine aminotransferase activity was significantly higher in the group of patients.", "contents": "[Serum lipids in Down's syndrome]. In 28 patients with Down syndrome and in 28 controls matched for age and sex serum lipoproteins and their main lipid constituents were determined. Both groups comprised subjects living in the same institutions for mentally retarded No significant differences were found between the two groups in total serum lipids, triglycerides, total cholesterol and phospholipid levels and in the proportion of esterified cholesterol and beta-lipoproteins. No characteristic pattern of alpha and beta lipoproteins could be observed in patients with Down syndrome by means of electrophoresis in polyacrylamide gel. Alanine aminotransferase activity was significantly higher in the group of patients."} {"id": "PMID:183166", "title": "Sleep EEG and motor activity as indicators in affective states.", "content": "This report reviews a number of studies which support our current classification schema for affective disorders. This classification differentiates between an anxious-hyperactive type and an anergic-hypoactive type which are then further subdivided into primary and secondary affective disorders. While the motor and activity measurements are for the most part limited to patients suffering from primary affective disease, current studies under way indicate that secondary affective disorders may also have characteristic biologic changes. EEG sleep and motor activity parameters provide useful pointers for differential diagnosis and treatment while having the added advantage of diminishing the clinician's almost exclusive dependency on amnestic data and the psychological observations made on the patient's behavior.", "contents": "Sleep EEG and motor activity as indicators in affective states. This report reviews a number of studies which support our current classification schema for affective disorders. This classification differentiates between an anxious-hyperactive type and an anergic-hypoactive type which are then further subdivided into primary and secondary affective disorders. While the motor and activity measurements are for the most part limited to patients suffering from primary affective disease, current studies under way indicate that secondary affective disorders may also have characteristic biologic changes. EEG sleep and motor activity parameters provide useful pointers for differential diagnosis and treatment while having the added advantage of diminishing the clinician's almost exclusive dependency on amnestic data and the psychological observations made on the patient's behavior."} {"id": "PMID:183167", "title": "The effect of ACTH treatment on lymphocyte subpopulations in patients with myasthenia gravis.", "content": "Blood lymphocytes were collected before, at various times during treatment and after treatment with ACTH in patients with myasthenia gravis. The relative proportions of thymus-derived (T cells) and bursa-derived (B cells) lymphocytes were determined. Eight of nine patients had a relative increase in B cells, whereas T cells showed a relative decrease. Myasthenic symptoms in these eight patients also were relieved. One patient who was not thymectomized showed virtually no relief in symptoms nor any changes in the relative T and B cell proportions or numbers, indicating a close association between the disease and the thymus-derived immune system.", "contents": "The effect of ACTH treatment on lymphocyte subpopulations in patients with myasthenia gravis. Blood lymphocytes were collected before, at various times during treatment and after treatment with ACTH in patients with myasthenia gravis. The relative proportions of thymus-derived (T cells) and bursa-derived (B cells) lymphocytes were determined. Eight of nine patients had a relative increase in B cells, whereas T cells showed a relative decrease. Myasthenic symptoms in these eight patients also were relieved. One patient who was not thymectomized showed virtually no relief in symptoms nor any changes in the relative T and B cell proportions or numbers, indicating a close association between the disease and the thymus-derived immune system."} {"id": "PMID:183168", "title": "\"Giant axonal neuropathy\" caused by industrial chemicals: neurofilamentous axonal masses in man.", "content": "Symmetrical polyneuropathy developed in two patients after they had been in contact with acrylamide and methyl n-butyl ketone, respectively. In sural nerve biopsy material from both patients, electron microscopy showed frequent focal axonal swellings containing masses of neurofilaments. Some axons undergoing axonal degeneration also were seen. These morphologic features are identical to those produced in experimental animals after exposure to these chemicals and are similar to those found in n-hexane neuropathy and in the three reported cases of giant axonal neuropathy. Sural nerve biopsy is an important diagnostic test in identifying cases of peripheral neuropathy caused by these chemicals.", "contents": "\"Giant axonal neuropathy\" caused by industrial chemicals: neurofilamentous axonal masses in man. Symmetrical polyneuropathy developed in two patients after they had been in contact with acrylamide and methyl n-butyl ketone, respectively. In sural nerve biopsy material from both patients, electron microscopy showed frequent focal axonal swellings containing masses of neurofilaments. Some axons undergoing axonal degeneration also were seen. These morphologic features are identical to those produced in experimental animals after exposure to these chemicals and are similar to those found in n-hexane neuropathy and in the three reported cases of giant axonal neuropathy. Sural nerve biopsy is an important diagnostic test in identifying cases of peripheral neuropathy caused by these chemicals."} {"id": "PMID:183169", "title": "Hereditary sensory neuropathy and tonic pupils.", "content": "The clinical features of two siblings with both hereditary sensory neuropathy and bilateral tonic pupils are described. Other neurologic disorders associated with tonic pupils are reviewed. Our patients appear to represent a unique instance of the association of disorders that primarily affect the ciliary and dorsal root ganglia.", "contents": "Hereditary sensory neuropathy and tonic pupils. The clinical features of two siblings with both hereditary sensory neuropathy and bilateral tonic pupils are described. Other neurologic disorders associated with tonic pupils are reviewed. Our patients appear to represent a unique instance of the association of disorders that primarily affect the ciliary and dorsal root ganglia."} {"id": "PMID:183170", "title": "The childhood type of dermatomyositis.", "content": "The childhood type fo dermatomyositis, which occurs in children and young adults, shows a specific constellation of pathologic changes in muscle. Capillary necrosis leads to capillary loss, generally starting on the periphery of muscle fascicles. Electron microscopy discloses undulating tubules in endothelial cells, lymphocytes, pericytes, and pseudosatellite cells. The muscle fiber damage is coextensive with capillary damage and probably results from progressive ischemia. The muscle cells, before atrophying, show mitochondrial elongation, Z disk streaming, focal myofibrillary loss, and occassionally selective thick filament loss. Muscle cell necrosis is rare and limited to infarctlike lesions. Inflammatory infiltrates, if present, occur only in connective tissue septa. The cause of the capillary damage has not been determined.", "contents": "The childhood type of dermatomyositis. The childhood type fo dermatomyositis, which occurs in children and young adults, shows a specific constellation of pathologic changes in muscle. Capillary necrosis leads to capillary loss, generally starting on the periphery of muscle fascicles. Electron microscopy discloses undulating tubules in endothelial cells, lymphocytes, pericytes, and pseudosatellite cells. The muscle fiber damage is coextensive with capillary damage and probably results from progressive ischemia. The muscle cells, before atrophying, show mitochondrial elongation, Z disk streaming, focal myofibrillary loss, and occassionally selective thick filament loss. Muscle cell necrosis is rare and limited to infarctlike lesions. Inflammatory infiltrates, if present, occur only in connective tissue septa. The cause of the capillary damage has not been determined."} {"id": "PMID:183171", "title": "Peripheral motor and sensory neuropathy of early childhood, simulating Werdnig-Hoffmann disease.", "content": "A five-year-old girl developed neurogenic muscular atrophy during infancy. On the basis of clinical findings and a muscle biopsy study a diagnosis of infantile spinal muscular atrophy, benign type II, was entertained. As the disease progressed, involvement of sensory pathways was detected by electrophysiological studies. Examination of a sural nerve specimen suggested a chronic polyneuropathy rather than spinal muscular atrophy. These findings were confirmed at autopsy by demonstrating severe loss of myelinated axons in ventral and dorsal spinal roots, peripheral nerves and dorsal columns of the spinal cord. In addition, islands of astroglial fibers were found in ventral and dorsal spinal roots, regarded as a secondary reaction to the breakdown of myelinated axons. This unusual scarring process seems to result from nerve fiber loss during the perinatal period, since radicular glial scar tissue is not known to occur in the spinal muscular atrophies of later onset. Examination of the sensory nervous system in patients with Werdnig-Hoffmann disease appears mandatory to clarify the precise disease entity leading to infantile neurogenic muscular atrophy.", "contents": "Peripheral motor and sensory neuropathy of early childhood, simulating Werdnig-Hoffmann disease. A five-year-old girl developed neurogenic muscular atrophy during infancy. On the basis of clinical findings and a muscle biopsy study a diagnosis of infantile spinal muscular atrophy, benign type II, was entertained. As the disease progressed, involvement of sensory pathways was detected by electrophysiological studies. Examination of a sural nerve specimen suggested a chronic polyneuropathy rather than spinal muscular atrophy. These findings were confirmed at autopsy by demonstrating severe loss of myelinated axons in ventral and dorsal spinal roots, peripheral nerves and dorsal columns of the spinal cord. In addition, islands of astroglial fibers were found in ventral and dorsal spinal roots, regarded as a secondary reaction to the breakdown of myelinated axons. This unusual scarring process seems to result from nerve fiber loss during the perinatal period, since radicular glial scar tissue is not known to occur in the spinal muscular atrophies of later onset. Examination of the sensory nervous system in patients with Werdnig-Hoffmann disease appears mandatory to clarify the precise disease entity leading to infantile neurogenic muscular atrophy."} {"id": "PMID:183172", "title": "The diagnosis of infantile generalized ceroidlipofuscinosis (type Hagberg-Santavuori) using skin biopsy.", "content": "Skin biopsies were performed in two cases of infantile generalized ceroidlipofuscinosis. In the first case the biopsy was done at the age of 8 years and the diagnosis was confirmed shortly thereafter by a postmortem examination. In the second case, the biopsy was performed much earlier (27 months) at a time when the diagnosis was not suspected; it was subsequently confirmed by similar findings in a neuro-muscular biopsy. In both cases, numerous cytoplasmic inclusions with granular osmiophilic deposits were present in epidermal cells, eccrine sweat glands, smooth muscle cells, nurve fascicles, fibroblasts and vascular elements while none were found in age-matched controls. As already stressed by Anzil et al. (1975), the morphology of the inclusions can be heterogeneous and linear profiles were often observed, mainly in the cytosomes present in the vascular cells. We feel confident that a diagnosis of infantile generalized ceroid-lipofuscinosis can be made by skin biopsy obviating therefore the need for other surgical procedures.", "contents": "The diagnosis of infantile generalized ceroidlipofuscinosis (type Hagberg-Santavuori) using skin biopsy. Skin biopsies were performed in two cases of infantile generalized ceroidlipofuscinosis. In the first case the biopsy was done at the age of 8 years and the diagnosis was confirmed shortly thereafter by a postmortem examination. In the second case, the biopsy was performed much earlier (27 months) at a time when the diagnosis was not suspected; it was subsequently confirmed by similar findings in a neuro-muscular biopsy. In both cases, numerous cytoplasmic inclusions with granular osmiophilic deposits were present in epidermal cells, eccrine sweat glands, smooth muscle cells, nurve fascicles, fibroblasts and vascular elements while none were found in age-matched controls. As already stressed by Anzil et al. (1975), the morphology of the inclusions can be heterogeneous and linear profiles were often observed, mainly in the cytosomes present in the vascular cells. We feel confident that a diagnosis of infantile generalized ceroid-lipofuscinosis can be made by skin biopsy obviating therefore the need for other surgical procedures."} {"id": "PMID:183173", "title": "[Generalized infantile neuroaxonal dystrophies with pigmentation and lipophanerosis of the pallidum in concordant twins (author's transl)].", "content": "Monozygotic male twins died at the age of 6 1/2 and 7 1/2 years respectively after a progressive course of mental deterioration, hypotonia, spasticity, optic atrophy and seizures that had commenced at the age of 2 years. Both patients showed generalized neuroaxonal dystrophy (NAD), marked by numerous spheroids, iron-positive pigment and lipophanerosis of the pallidum. NAD can be classified as a generalized form without pigmentation of the pallidum (infantile type of Seitelberger), a juvenile type of Rozdilsky, a generalized form with pigmentation (cases described here), and localized forms (infantile, late infantile, juvenile = classic Hallervorden-Spatz disease, adult types).", "contents": "[Generalized infantile neuroaxonal dystrophies with pigmentation and lipophanerosis of the pallidum in concordant twins (author's transl)]. Monozygotic male twins died at the age of 6 1/2 and 7 1/2 years respectively after a progressive course of mental deterioration, hypotonia, spasticity, optic atrophy and seizures that had commenced at the age of 2 years. Both patients showed generalized neuroaxonal dystrophy (NAD), marked by numerous spheroids, iron-positive pigment and lipophanerosis of the pallidum. NAD can be classified as a generalized form without pigmentation of the pallidum (infantile type of Seitelberger), a juvenile type of Rozdilsky, a generalized form with pigmentation (cases described here), and localized forms (infantile, late infantile, juvenile = classic Hallervorden-Spatz disease, adult types)."} {"id": "PMID:183174", "title": "Effect of reticuloendothelial stimulators on the tissue changes and evolution of experimental atheroma in rabbits.", "content": "Administration of histamine phosphate or glycerol trioleate (RE stimulators) to cholesterol-fed rabbits induced identical pattern of changes in cholesterol, phospholipid and triglyceride levels of the blood. However, the incidence of atheroma index in aorta and coronary arteries were significantly higher in histamine-treated and glycerol-trioleate-treated animals compared to cholesterol-fed controls. The rise in these indices appeared to be only partly related to increase in serum beta-lipoproteins but mostly due to increased permeability of the endothelium and internal elastic lamina probably caused by histamine phosphate and glycerol trioleate resulted in greater degree of atheromatous lesions in those groups.", "contents": "Effect of reticuloendothelial stimulators on the tissue changes and evolution of experimental atheroma in rabbits. Administration of histamine phosphate or glycerol trioleate (RE stimulators) to cholesterol-fed rabbits induced identical pattern of changes in cholesterol, phospholipid and triglyceride levels of the blood. However, the incidence of atheroma index in aorta and coronary arteries were significantly higher in histamine-treated and glycerol-trioleate-treated animals compared to cholesterol-fed controls. The rise in these indices appeared to be only partly related to increase in serum beta-lipoproteins but mostly due to increased permeability of the endothelium and internal elastic lamina probably caused by histamine phosphate and glycerol trioleate resulted in greater degree of atheromatous lesions in those groups."} {"id": "PMID:183175", "title": "Molecular biology and oral contraception.", "content": "Recent developments in knowledge of sex hormone receptors and steroid analogue metabolism allow a rational selection of oral contraceptive steroids from among the numerous available products. Dose related metabolic effects of synthetic estrogens have been demonstrated. Many of these estrogenic actions are antagonised by norgestrel but not by any other commercially available progestogen. Generalised activation of lysosomal enzymes can be demonstrated in oral contraceptive users and is shown to be related to the total steroid dose per cycle, rather than to particular products. These findings suggest that the lowest dose combination of ethynylestradiol and d-norgestrel is the product of choice. Clinical results with such a product are described.", "contents": "Molecular biology and oral contraception. Recent developments in knowledge of sex hormone receptors and steroid analogue metabolism allow a rational selection of oral contraceptive steroids from among the numerous available products. Dose related metabolic effects of synthetic estrogens have been demonstrated. Many of these estrogenic actions are antagonised by norgestrel but not by any other commercially available progestogen. Generalised activation of lysosomal enzymes can be demonstrated in oral contraceptive users and is shown to be related to the total steroid dose per cycle, rather than to particular products. These findings suggest that the lowest dose combination of ethynylestradiol and d-norgestrel is the product of choice. Clinical results with such a product are described."} {"id": "PMID:183176", "title": "Herpetiform ulceration.", "content": "The rationale for the clinical existence of a less commonly found form of recurrent oral ulceration, herpetiform ulceration (HFU), is presented, illustrated by six clinical cases. The clinical and laboratory features that separate it from recurrent herpetic ulceration (RHU) and recurrent minor aphthous ulceration (RHU) are discussed. Although a viral cause has been proposed for the condition, based on the finding of intranuclear bodies, electron microscopic and other laboratory investigations by the authors indicate that there is insufficient evidence at present to confirm this. Since HFU does have a significant number of histologic and immunologic features in common with recurrent apthous ulceration, it is thought that it should be considered to be a variant of this condition until the true cause of it is revealed.", "contents": "Herpetiform ulceration. The rationale for the clinical existence of a less commonly found form of recurrent oral ulceration, herpetiform ulceration (HFU), is presented, illustrated by six clinical cases. The clinical and laboratory features that separate it from recurrent herpetic ulceration (RHU) and recurrent minor aphthous ulceration (RHU) are discussed. Although a viral cause has been proposed for the condition, based on the finding of intranuclear bodies, electron microscopic and other laboratory investigations by the authors indicate that there is insufficient evidence at present to confirm this. Since HFU does have a significant number of histologic and immunologic features in common with recurrent apthous ulceration, it is thought that it should be considered to be a variant of this condition until the true cause of it is revealed."} {"id": "PMID:183177", "title": "Clinical and ultrastructural study of Burkitt-like leukaemia.", "content": "Six patients, two with acute lymphoblastic leukaemia (A.L.L.) and four with lymphosarcoma with early transformation into A.L.L., have been studied. All blast-cells demonstrated with cytological, cytochemical and ultrastructural features of Burkitt's tumour. The clinical evolution was fulminant and there was no remission of long duration despite intensive chemotherapy. The cytoplasm of the blast-cells displayed a great number of lipid droplets. The level of the anticapsid Epstein-Barr virus antibodies was high in the case investigated.", "contents": "Clinical and ultrastructural study of Burkitt-like leukaemia. Six patients, two with acute lymphoblastic leukaemia (A.L.L.) and four with lymphosarcoma with early transformation into A.L.L., have been studied. All blast-cells demonstrated with cytological, cytochemical and ultrastructural features of Burkitt's tumour. The clinical evolution was fulminant and there was no remission of long duration despite intensive chemotherapy. The cytoplasm of the blast-cells displayed a great number of lipid droplets. The level of the anticapsid Epstein-Barr virus antibodies was high in the case investigated."} {"id": "PMID:183178", "title": "Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature.", "content": "A total of 130 patients with uncomplicated short stature (4 to 17 years of age) were treated with oxandrolone, 0.25 mg/kg/day, for up to four years. Oxandrolone therapy resulted in a two-fold increase in mean growth velocity in the first six months of therapy and was an effective growth stimulant for the full four-year period. There was no overall adverse effect of oxandrolone on post-treatment mean growth velocity or on skeletal maturation relative to height gain. There were 37 patients with greater increase in height age than bone age and 22 patients with greater increase in bone age than height age. Assessment of the contribution of oxandrolone therapy to the latter group is difficult because of inadequate methodology and the wide variation in individual growth patterns. Taken in their entirety, the data suggest that oxandrolone is useful in the prolonged treatment of uncomplicated short stature and is not associated with undesirable acceleration of skeletal maturation.", "contents": "Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature. A total of 130 patients with uncomplicated short stature (4 to 17 years of age) were treated with oxandrolone, 0.25 mg/kg/day, for up to four years. Oxandrolone therapy resulted in a two-fold increase in mean growth velocity in the first six months of therapy and was an effective growth stimulant for the full four-year period. There was no overall adverse effect of oxandrolone on post-treatment mean growth velocity or on skeletal maturation relative to height gain. There were 37 patients with greater increase in height age than bone age and 22 patients with greater increase in bone age than height age. Assessment of the contribution of oxandrolone therapy to the latter group is difficult because of inadequate methodology and the wide variation in individual growth patterns. Taken in their entirety, the data suggest that oxandrolone is useful in the prolonged treatment of uncomplicated short stature and is not associated with undesirable acceleration of skeletal maturation."} {"id": "PMID:183179", "title": "Eye color and responsiveness to arousing stimuli.", "content": "The hypothesis was advanced that dark-eyed subjects are more responsive to arousing stimuli than light-eyed subjects. 40 subjects listened to neutral and arousing auditory stimuli and viewed scenes which were neutral, violent, or sexual in nature. The dependent measure of arousal was a score derived from a combination of physiological responses recorded on a polygraph. Scores were significantly higher for dark-eyed than light-eyed subjects. Significant sex differences were also found, females having higher scores than males. Implications for future research and application were discussed.", "contents": "Eye color and responsiveness to arousing stimuli. The hypothesis was advanced that dark-eyed subjects are more responsive to arousing stimuli than light-eyed subjects. 40 subjects listened to neutral and arousing auditory stimuli and viewed scenes which were neutral, violent, or sexual in nature. The dependent measure of arousal was a score derived from a combination of physiological responses recorded on a polygraph. Scores were significantly higher for dark-eyed than light-eyed subjects. Significant sex differences were also found, females having higher scores than males. Implications for future research and application were discussed."} {"id": "PMID:183180", "title": "Disappearance of insulin response after enzymatic treatment of sodium-transporting amphibian epithelia.", "content": "Amphibian epithelia specialized in trans-cellular sodium transport lose their capacity to react to insulin by a stimulation of this process upon treatment with collagenase; baseline activity and responsiveness to other hormones (vasopressin, aldosterone) bringing about such a stimulation are preserved. This renders it likely that proteases contaminating most collagenase preparations exert a detrimental effect on the receptors held responsible for interaction between insulin and its target cells in the tissues examined.", "contents": "Disappearance of insulin response after enzymatic treatment of sodium-transporting amphibian epithelia. Amphibian epithelia specialized in trans-cellular sodium transport lose their capacity to react to insulin by a stimulation of this process upon treatment with collagenase; baseline activity and responsiveness to other hormones (vasopressin, aldosterone) bringing about such a stimulation are preserved. This renders it likely that proteases contaminating most collagenase preparations exert a detrimental effect on the receptors held responsible for interaction between insulin and its target cells in the tissues examined."} {"id": "PMID:183181", "title": "Effects of glutamate, aspartate, and two-presumed antagonists on feline rubrospinal neurones.", "content": "The actions of dicarboxyl amino acids (GLUT, ASP, DLH) and of presumed amino acid antagonists (GDEE, HA 966) were studied in rubrospinal neurones with microelectrophoretic techniques. ASP and GLUT depolarized reversibly the cell membrane and increased its conductance. ASP had slightly stronger actions than GLUT. DLH had strong depolarizing actions without a clearcut change in membrane conductance; this may be due to the fact that DLH effects do not involve synaptic receptors. A specific action as antagonists for GLUT could not be shown for GDEE or HA 966. HA 966 effects were often accompanied by apparent postsynaptic actions. GDEE antagonized DLH effects sometimes even stronger than GLUT effects. The effects of GLUT and ASP are in principal agreement with a function as excitatory transmitters. The demonstration of a role as transmitter substances in excitatory (e.g. corticorubral or interpositorubral) pathways, however, still awaits the specific pharmacological antagonist.", "contents": "Effects of glutamate, aspartate, and two-presumed antagonists on feline rubrospinal neurones. The actions of dicarboxyl amino acids (GLUT, ASP, DLH) and of presumed amino acid antagonists (GDEE, HA 966) were studied in rubrospinal neurones with microelectrophoretic techniques. ASP and GLUT depolarized reversibly the cell membrane and increased its conductance. ASP had slightly stronger actions than GLUT. DLH had strong depolarizing actions without a clearcut change in membrane conductance; this may be due to the fact that DLH effects do not involve synaptic receptors. A specific action as antagonists for GLUT could not be shown for GDEE or HA 966. HA 966 effects were often accompanied by apparent postsynaptic actions. GDEE antagonized DLH effects sometimes even stronger than GLUT effects. The effects of GLUT and ASP are in principal agreement with a function as excitatory transmitters. The demonstration of a role as transmitter substances in excitatory (e.g. corticorubral or interpositorubral) pathways, however, still awaits the specific pharmacological antagonist."} {"id": "PMID:183184", "title": "Distribution of estrogen receptors in subfractions of hen oviduct chromatin.", "content": "Hen oviduct chromatin was digested with DNase II and separated into two fractions. The MgCl2 insoluble chromatin fraction (43% of the total DNA) was enriched in nucleosome-like particles, which sedimented at 11 S and contained 185 base pairs of DNA. The MgCl2 soluble chromatin fraction (5% of the total DNA) was characterized by 5 S and 14 S peaks in sucrose gradients; Estrogen receptors in the chromatin fractions were labelled with [3H] estradiol using the steroid exchange assay. The concentration of receptors in the MgCl2 soluble chromatin was 4;5 times higher than that in the MgCl2 insoluble chromatinmin sucrose gradient analysis the 11 S particles displayed a negligible specific radioactivity suggesting that estrogen receptors mainly bind to extranucleosomal chromatin.", "contents": "Distribution of estrogen receptors in subfractions of hen oviduct chromatin. Hen oviduct chromatin was digested with DNase II and separated into two fractions. The MgCl2 insoluble chromatin fraction (43% of the total DNA) was enriched in nucleosome-like particles, which sedimented at 11 S and contained 185 base pairs of DNA. The MgCl2 soluble chromatin fraction (5% of the total DNA) was characterized by 5 S and 14 S peaks in sucrose gradients; Estrogen receptors in the chromatin fractions were labelled with [3H] estradiol using the steroid exchange assay. The concentration of receptors in the MgCl2 soluble chromatin was 4;5 times higher than that in the MgCl2 insoluble chromatinmin sucrose gradient analysis the 11 S particles displayed a negligible specific radioactivity suggesting that estrogen receptors mainly bind to extranucleosomal chromatin."} {"id": "PMID:183185", "title": "Effect of treatment in vivo with N,N-dimethylnitrosamine or methyl methanesulphonate on the cytoplasmic DNA polymerase of regenerating rat liver.", "content": "A 10-16 fold increase in rat liver cytoplasmic DNA polymerase (DNA polymerase-alpha) was observed by 24 hrs after two thirds partial hepatectomy. Injection of either N,N-dimethylnitrosamine (DMN) or methyl methanesulphonate (MMS) At 6 or 12 hrs after partial hepatectomy completely inhibited this increased production of polymerase, but when given at 20 hours they had less effect. Neither compound altered the molecular size distribution of the enzyme. These data indicate that the lowered levels of DNA polymerase-alpha could play a major role in the reduction in DNA synthesis which occurs after carcinogen treatment.", "contents": "Effect of treatment in vivo with N,N-dimethylnitrosamine or methyl methanesulphonate on the cytoplasmic DNA polymerase of regenerating rat liver. A 10-16 fold increase in rat liver cytoplasmic DNA polymerase (DNA polymerase-alpha) was observed by 24 hrs after two thirds partial hepatectomy. Injection of either N,N-dimethylnitrosamine (DMN) or methyl methanesulphonate (MMS) At 6 or 12 hrs after partial hepatectomy completely inhibited this increased production of polymerase, but when given at 20 hours they had less effect. Neither compound altered the molecular size distribution of the enzyme. These data indicate that the lowered levels of DNA polymerase-alpha could play a major role in the reduction in DNA synthesis which occurs after carcinogen treatment."} {"id": "PMID:183182", "title": "[The influence of infectious bronchitis virus on egg production, fertility, hatchability and mortality rate in chickens (author's transl)].", "content": "In 35 flocks comprising almost 100,000 White Plymouth Rock birds producing hatching eggs, infectious bronchitis (IB) caused a decline in production which appeared to be connected with the age of the birds, when the outbreak started (table I). In outbreaks of IB in pullets 3-4 weeks before they are ready to lay there is a considerable risk of delay of production and a generally too low yield (fig 1). Egg laying birds, 25-34 weeks of age, suffered a drop in production from 20-80% (on an average 40%) and normal yield was never regained. After 6-8 weeks the production rate usually stabilizes around 6-12% below normal production. IB outbreaks in the middle of the production period (35-45 weeks) resulted in a decline of egg production of 40-90% (on an average 55%). Recovery of production usually occurred after 6-8 weeks (fig. 2). Observations of clinically typical outbreaks without any laboratory verification indicate that IB outbreaks at the end of the egg production period resulted in irreparable decline of production. Marked alterations in exterior and interior quality of the egg have been observed. Both mishapen appearance, rough and thin shell, bleached shell color and watery albumen have occurred. These facts did sometimes cause transient increased \"sorting out\" of haching eggs. Also fertility rate was noticed to be affected temporarily during and after an attack of IB. In 17 flocks drops of 1.7-22.4% (on an average 7.4%) were registered (fig. 3). Also hatchability decreased 3.0-43.8% (on an average 13.7%) (fig. 4). In most of the registered outbreaks of IB the weekly mortality remained below 1%, but in single cases the figure could rise up to about 4% (fig. 5), most often in flocks where complicating factors such as secondary infections caused by E. coli or M. gallisepticum were present.", "contents": "[The influence of infectious bronchitis virus on egg production, fertility, hatchability and mortality rate in chickens (author's transl)]. In 35 flocks comprising almost 100,000 White Plymouth Rock birds producing hatching eggs, infectious bronchitis (IB) caused a decline in production which appeared to be connected with the age of the birds, when the outbreak started (table I). In outbreaks of IB in pullets 3-4 weeks before they are ready to lay there is a considerable risk of delay of production and a generally too low yield (fig 1). Egg laying birds, 25-34 weeks of age, suffered a drop in production from 20-80% (on an average 40%) and normal yield was never regained. After 6-8 weeks the production rate usually stabilizes around 6-12% below normal production. IB outbreaks in the middle of the production period (35-45 weeks) resulted in a decline of egg production of 40-90% (on an average 55%). Recovery of production usually occurred after 6-8 weeks (fig. 2). Observations of clinically typical outbreaks without any laboratory verification indicate that IB outbreaks at the end of the egg production period resulted in irreparable decline of production. Marked alterations in exterior and interior quality of the egg have been observed. Both mishapen appearance, rough and thin shell, bleached shell color and watery albumen have occurred. These facts did sometimes cause transient increased \"sorting out\" of haching eggs. Also fertility rate was noticed to be affected temporarily during and after an attack of IB. In 17 flocks drops of 1.7-22.4% (on an average 7.4%) were registered (fig. 3). Also hatchability decreased 3.0-43.8% (on an average 13.7%) (fig. 4). In most of the registered outbreaks of IB the weekly mortality remained below 1%, but in single cases the figure could rise up to about 4% (fig. 5), most often in flocks where complicating factors such as secondary infections caused by E. coli or M. gallisepticum were present."} {"id": "PMID:183186", "title": "Joining of ribooligonucleotides with T4 RNA ligase and identification of the oligonucleotide-adenylate intermediate.", "content": "T4 RNA ligase was found to join A-A-A-A-A-A and 32pU-U-U-U in the presence of ATP as cofactor. In this reaction the pyrophosphate of pU-U-U-U and pA was isolated by chromatography on a RPC-5 column, besides the joined product and the starting materials. This pyrophosphate was shown to be an intermediate in the joining reaction because of the fact that coupling with A-A-A-A-A-A to give the decanucleotide could be performed in the absence of ATP. The structure of the oligonucleotide-adenylate was determined by enzymatic digestion with base-nonspecific nuclease and venom phosphodiesterase. Futher evidence for the proposed structure was obtained by isolation of the intermediate obtained by using pU-U-U-U and [alpha-32p]ATP. This pyrophosphate gave pA and pU by treatment with venom phosphodiesterase. Several other joining reactions between various purine- and pyrimidine ribooligonucleotides to 5'-phosphorylated ribooligonucleotides are discussed.", "contents": "Joining of ribooligonucleotides with T4 RNA ligase and identification of the oligonucleotide-adenylate intermediate. T4 RNA ligase was found to join A-A-A-A-A-A and 32pU-U-U-U in the presence of ATP as cofactor. In this reaction the pyrophosphate of pU-U-U-U and pA was isolated by chromatography on a RPC-5 column, besides the joined product and the starting materials. This pyrophosphate was shown to be an intermediate in the joining reaction because of the fact that coupling with A-A-A-A-A-A to give the decanucleotide could be performed in the absence of ATP. The structure of the oligonucleotide-adenylate was determined by enzymatic digestion with base-nonspecific nuclease and venom phosphodiesterase. Futher evidence for the proposed structure was obtained by isolation of the intermediate obtained by using pU-U-U-U and [alpha-32p]ATP. This pyrophosphate gave pA and pU by treatment with venom phosphodiesterase. Several other joining reactions between various purine- and pyrimidine ribooligonucleotides to 5'-phosphorylated ribooligonucleotides are discussed."} {"id": "PMID:183187", "title": "Comprehensive care of the ileostomy patient.", "content": "Comprehensive care of the person with an ileostomy is an integral part of professional nursing. It is the responsibility of professional nurses to be knowledgeable and skilled in ileostomy patient care. This article has presented basic issues to be considered in facilitating the rehabilitation of the person with an ileostomy. Perhaps the most important factor to be considered is that the process of rehabilitation must begin at the first encounter with the person undergoing ileostomy surgery, must extend beyond the period of hospitalization, and must reach into the person's home and community.", "contents": "Comprehensive care of the ileostomy patient. Comprehensive care of the person with an ileostomy is an integral part of professional nursing. It is the responsibility of professional nurses to be knowledgeable and skilled in ileostomy patient care. This article has presented basic issues to be considered in facilitating the rehabilitation of the person with an ileostomy. Perhaps the most important factor to be considered is that the process of rehabilitation must begin at the first encounter with the person undergoing ileostomy surgery, must extend beyond the period of hospitalization, and must reach into the person's home and community."} {"id": "PMID:183183", "title": "[Necrotizing enteritis and geophagia].", "content": "Two cases of intestinal perforation due to necrotising enteritis in patients with pica are presented. The aetiopathogenesis of pica is discussed as well as its role in the development of necrotising enteritis.", "contents": "[Necrotizing enteritis and geophagia]. Two cases of intestinal perforation due to necrotising enteritis in patients with pica are presented. The aetiopathogenesis of pica is discussed as well as its role in the development of necrotising enteritis."} {"id": "PMID:183191", "title": "Effect of dehydration of the cornea with experimentally induced ulcer on collagenase activity.", "content": "In the course of healing of experimental ulcer one could observe a distinct difference between a cornea, subjected to the action of glycerol and a control one. The damage to the chemical structure of collagenous fibers was much smaller than in the control. On the basis of the investigations performed one may conclude that glycerol, through dehydration of the corneal tissue and stimulation of mucopolysaccharide synthesis, suppresses the activity of collagenase. In polarized light this process was manifested by the double refraction phenomenon and in clinical observation--by an accelerated healing of ulcer.", "contents": "Effect of dehydration of the cornea with experimentally induced ulcer on collagenase activity. In the course of healing of experimental ulcer one could observe a distinct difference between a cornea, subjected to the action of glycerol and a control one. The damage to the chemical structure of collagenous fibers was much smaller than in the control. On the basis of the investigations performed one may conclude that glycerol, through dehydration of the corneal tissue and stimulation of mucopolysaccharide synthesis, suppresses the activity of collagenase. In polarized light this process was manifested by the double refraction phenomenon and in clinical observation--by an accelerated healing of ulcer."} {"id": "PMID:183192", "title": "Histiocytoma; histiocytoma proliferans; histiocytoma malignum: (clinical and morphological observations).", "content": "In a group of 112 cases of histiocytic neoplasms treated 1960--1973 103 benign tumors (histiocytoma), 3 semimalignant tumors (histiocytoma proliferans), and 6 malignant ones (histiocytoma malignum) were diagnosed. Clinical and morphological examinations indicate that under the influence of stimuli histiocytoma may undergo a biological transformation developing into less mature forms such as histiocytoma proliferans and histiocytoma malignum. The treatment of malignant tumors consisted in their removal together with a wide margin or adjacent tissues. In 2 cases enlarged lymph nodes were removed but no metastases were found. In one case death occurred 3 years after operation as a result of distant metastases.", "contents": "Histiocytoma; histiocytoma proliferans; histiocytoma malignum: (clinical and morphological observations). In a group of 112 cases of histiocytic neoplasms treated 1960--1973 103 benign tumors (histiocytoma), 3 semimalignant tumors (histiocytoma proliferans), and 6 malignant ones (histiocytoma malignum) were diagnosed. Clinical and morphological examinations indicate that under the influence of stimuli histiocytoma may undergo a biological transformation developing into less mature forms such as histiocytoma proliferans and histiocytoma malignum. The treatment of malignant tumors consisted in their removal together with a wide margin or adjacent tissues. In 2 cases enlarged lymph nodes were removed but no metastases were found. In one case death occurred 3 years after operation as a result of distant metastases."} {"id": "PMID:183203", "title": "Regulation of active alpha-aminoisobutyric acid transport expressed in membrane vesicles from mouse fibroblasts.", "content": "Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and from those transformed by simian virus 40 catalyzed carrier-mediated uptake of L-alpha-aminoisobutyric acid. Concentrative uptake required the presence of a Na+ gradient (external Na+ greater than internal Na+) and occurred independently of endogenous (Na+ + K+) ATPase activity. This process is electrogenic, since uptake was stimulated by a K+ diffusion gradient (internal greater external) in the presence of valinomycin or by the addition of the Na+ salt of a permeant ion, conditions expected to create an interior-negative membrane potential. Both the initial rate of concentrative uptake of L-alpha-aminoisobutyric acid and its maximal accumulation, driven by a standard Na+ gradient, were decreased in vesicles from density-inhibited, untransformed cells and increased in those from cells transformed by simian virus 40 compared with vesicles from proliferating untransformed cells. An increased maximal velocity (Vmax) of uptake stimulated by Na+ gradient was observed in vesicles from transformed cells compared with those from untransformed cells, suggesting an increase in the number of carriers or in their mobility. Since the relative extent of accumulation of this model amino acid driven by a standard Na+ gradient also differed with growth or transformed status, an additional possibility for cellular regulation of this process could be alteration of membrane Na+ permeability or carrier response to Na+.", "contents": "Regulation of active alpha-aminoisobutyric acid transport expressed in membrane vesicles from mouse fibroblasts. Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and from those transformed by simian virus 40 catalyzed carrier-mediated uptake of L-alpha-aminoisobutyric acid. Concentrative uptake required the presence of a Na+ gradient (external Na+ greater than internal Na+) and occurred independently of endogenous (Na+ + K+) ATPase activity. This process is electrogenic, since uptake was stimulated by a K+ diffusion gradient (internal greater external) in the presence of valinomycin or by the addition of the Na+ salt of a permeant ion, conditions expected to create an interior-negative membrane potential. Both the initial rate of concentrative uptake of L-alpha-aminoisobutyric acid and its maximal accumulation, driven by a standard Na+ gradient, were decreased in vesicles from density-inhibited, untransformed cells and increased in those from cells transformed by simian virus 40 compared with vesicles from proliferating untransformed cells. An increased maximal velocity (Vmax) of uptake stimulated by Na+ gradient was observed in vesicles from transformed cells compared with those from untransformed cells, suggesting an increase in the number of carriers or in their mobility. Since the relative extent of accumulation of this model amino acid driven by a standard Na+ gradient also differed with growth or transformed status, an additional possibility for cellular regulation of this process could be alteration of membrane Na+ permeability or carrier response to Na+."} {"id": "PMID:183204", "title": "Handedness of crossover connections in beta sheets.", "content": "In a crossover connection, the polypeptide chain leaves one end of a beta sheet, forms a loop of any length and any conformation, and reenters the same beta sheet from the opposite end. Of the 85 examples of crossover connections which occur in the known protein structures, 83 are righthanded and only two are lefthanded. It is proposed that consistent handedness, even in long irregular loops, could be produced by the preferred twist direction of extended chain and the righthandedness of alpha-helices, provided certain conditions hold during the protein folding process.", "contents": "Handedness of crossover connections in beta sheets. In a crossover connection, the polypeptide chain leaves one end of a beta sheet, forms a loop of any length and any conformation, and reenters the same beta sheet from the opposite end. Of the 85 examples of crossover connections which occur in the known protein structures, 83 are righthanded and only two are lefthanded. It is proposed that consistent handedness, even in long irregular loops, could be produced by the preferred twist direction of extended chain and the righthandedness of alpha-helices, provided certain conditions hold during the protein folding process."} {"id": "PMID:183205", "title": "Appearance in vivo of single-stranded complementary ends on parental herpesvirus DNA.", "content": "Intracellular forms of pseudorabies virus parental DNA were examined before and after the onset of viral DNA synthesis. Before initiation of synthesis, parental viral DNA acquires single-stranded ends. Circular and concatemeric molecules are also observed, indicating that the single-stranded ends are complementary. Viral DNA replication is initiated at an internal site within the DNA molecule, giving rise to characteristic replicative loops with single-stranded regions in the trans position. Such replicative loops were seen in unit-size (and smaller than unit-size) linear molecules as well as in circular and concatemeric molecules. These results show that the parental viral DNA molecules that acquire single-stranded ends, and consequently are able to form circles and concatemers, proceed to replicate.", "contents": "Appearance in vivo of single-stranded complementary ends on parental herpesvirus DNA. Intracellular forms of pseudorabies virus parental DNA were examined before and after the onset of viral DNA synthesis. Before initiation of synthesis, parental viral DNA acquires single-stranded ends. Circular and concatemeric molecules are also observed, indicating that the single-stranded ends are complementary. Viral DNA replication is initiated at an internal site within the DNA molecule, giving rise to characteristic replicative loops with single-stranded regions in the trans position. Such replicative loops were seen in unit-size (and smaller than unit-size) linear molecules as well as in circular and concatemeric molecules. These results show that the parental viral DNA molecules that acquire single-stranded ends, and consequently are able to form circles and concatemers, proceed to replicate."} {"id": "PMID:183206", "title": "Calcium-dependent regulatory protein of cyclic nucleotide metabolism in normal and transformed chicken embryo fibroblasts.", "content": "The concentration of a calcium-binding protein modulator of 3':5'-cyclic-nucleotide phosphodiesterase (EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase) activity is increased in chicken embryo fibroblasts upon transformation by Rous sarcoma virus. This modulator protein from fibroblasts, which has roughly the same molecular size, charge, and functional properties as that isolated from chicken brain, comprises approximately 1.32% of the soluble protein in homogenates of fibroblasts infected and transformed by Rous sarcoma virus. In comparison, the modulator comprises approximately 0.30% of the soluble protein in homogenates of normal fibroblasts from confluent cultures and 0.36% of the soluble protein in homogenates of fibroblasts infected with a transformation-defective mutant of Rous sarcoma virus. Modulator levels in normal fibroblasts at subconfluent cell densities are 0.42-0.76% of the homogenate soluble protein, i.e., between that found in confluent normal fibroblasts and in fibroblasts transformed by Rous sarcoma virus. These observations suggest that the levels of the modulator protein are elevated under conditions in which chicken embryo fibroblasts are undergoing rapid growth and have decreased adenosine 3':5'-cyclic monophosphate levels.", "contents": "Calcium-dependent regulatory protein of cyclic nucleotide metabolism in normal and transformed chicken embryo fibroblasts. The concentration of a calcium-binding protein modulator of 3':5'-cyclic-nucleotide phosphodiesterase (EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase) activity is increased in chicken embryo fibroblasts upon transformation by Rous sarcoma virus. This modulator protein from fibroblasts, which has roughly the same molecular size, charge, and functional properties as that isolated from chicken brain, comprises approximately 1.32% of the soluble protein in homogenates of fibroblasts infected and transformed by Rous sarcoma virus. In comparison, the modulator comprises approximately 0.30% of the soluble protein in homogenates of normal fibroblasts from confluent cultures and 0.36% of the soluble protein in homogenates of fibroblasts infected with a transformation-defective mutant of Rous sarcoma virus. Modulator levels in normal fibroblasts at subconfluent cell densities are 0.42-0.76% of the homogenate soluble protein, i.e., between that found in confluent normal fibroblasts and in fibroblasts transformed by Rous sarcoma virus. These observations suggest that the levels of the modulator protein are elevated under conditions in which chicken embryo fibroblasts are undergoing rapid growth and have decreased adenosine 3':5'-cyclic monophosphate levels."} {"id": "PMID:183207", "title": "Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro.", "content": "Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C \"lacks\" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity.", "contents": "Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro. Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C \"lacks\" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity."} {"id": "PMID:183208", "title": "Direct biochemical mapping of eukaryotic viral DNA by means of a linked transcription-translation cell-free system.", "content": "A method is described for mapping regions of eukaryotic viral DNA coding for specific proteins, utilizing a linked transcription-translation cell-free system primed with DNA fragments generated by restriction endonucleases. Three simian virus 40 (SV40) DNA fragments derived from that region of the DNA expressed late in lytic infection were purified. They were: Hpa I-A (0.76-0.175 map units), Bgl I-EcoRI-B (0.672-0), and Hpa II-EcoRI-B (0.735-0). (Fragments are named from the cleaving restriction endonuclease and electrophoretic mobility. End positions on the conventional map are in clockwise order.) These fragments efficiently stimulated the incorporation of [3H]UTP and [35S]methionine into trichloroacetic-acid-insoluble material in the linkec system. The location of the region of DNA coding for the viral structural proteins VPI, VP2 and VP3 was determined from the spectrum of polypeptide synthesis directed by the individual intact fragments and their specific endonucleolytic digests. The polypeptides synthesized in the cell-free system were characterized on urea-sodium dodecyl sulfate polyacrylamide gradient gels and by two-dimensional tryptic peptide analysis. ..", "contents": "Direct biochemical mapping of eukaryotic viral DNA by means of a linked transcription-translation cell-free system. A method is described for mapping regions of eukaryotic viral DNA coding for specific proteins, utilizing a linked transcription-translation cell-free system primed with DNA fragments generated by restriction endonucleases. Three simian virus 40 (SV40) DNA fragments derived from that region of the DNA expressed late in lytic infection were purified. They were: Hpa I-A (0.76-0.175 map units), Bgl I-EcoRI-B (0.672-0), and Hpa II-EcoRI-B (0.735-0). (Fragments are named from the cleaving restriction endonuclease and electrophoretic mobility. End positions on the conventional map are in clockwise order.) These fragments efficiently stimulated the incorporation of [3H]UTP and [35S]methionine into trichloroacetic-acid-insoluble material in the linkec system. The location of the region of DNA coding for the viral structural proteins VPI, VP2 and VP3 was determined from the spectrum of polypeptide synthesis directed by the individual intact fragments and their specific endonucleolytic digests. The polypeptides synthesized in the cell-free system were characterized on urea-sodium dodecyl sulfate polyacrylamide gradient gels and by two-dimensional tryptic peptide analysis. .."} {"id": "PMID:183209", "title": "Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes.", "content": "Treatment of isolated rat hepatocytes with saturating concentrations of glucagon caused several modifications properties of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40): S0.5 (substrate concentration at half maximum velocity) for phosphoenolpyruvate was about doubled, whereas Vmax was not changed; the activity measured at 0.15 mM phosphoenolpyruvate (physiological concentration) was reduced 65-80%; and there was also an increase in the Hill coefficient and in the affinity of the enzyme for the inhibitors Mg-ATP and alanine. Glucagon, 3':5'-cyclic AMP, and epinephrine caused an inactivation of pyruvate kinase together with a sitmulation of gluconeogenesis. Insulin (10 nM) antagonized the effect of suboptimal doses of glucagon or cyclic AMP and of even maximal doses of epinephrine, on both pyruvate kinase activity and on gluconeogenesis. These observations can be explained by a phosphorylation of pyruvate kinase by cyclic-AMP-dependent protein kinase, as described by Ljungstr\u00f6m et al. [(1974) Biochim. Biophys. Acta 358, 289-298] in a reconstructed system. They offer a molecular explanation for the hormonal control of gluconeogenesis. Glucose caused an inhibition of gluconeogenesis with no corresponding change in pyruvate kinase activity.", "contents": "Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes. Treatment of isolated rat hepatocytes with saturating concentrations of glucagon caused several modifications properties of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40): S0.5 (substrate concentration at half maximum velocity) for phosphoenolpyruvate was about doubled, whereas Vmax was not changed; the activity measured at 0.15 mM phosphoenolpyruvate (physiological concentration) was reduced 65-80%; and there was also an increase in the Hill coefficient and in the affinity of the enzyme for the inhibitors Mg-ATP and alanine. Glucagon, 3':5'-cyclic AMP, and epinephrine caused an inactivation of pyruvate kinase together with a sitmulation of gluconeogenesis. Insulin (10 nM) antagonized the effect of suboptimal doses of glucagon or cyclic AMP and of even maximal doses of epinephrine, on both pyruvate kinase activity and on gluconeogenesis. These observations can be explained by a phosphorylation of pyruvate kinase by cyclic-AMP-dependent protein kinase, as described by Ljungstr\u00f6m et al. [(1974) Biochim. Biophys. Acta 358, 289-298] in a reconstructed system. They offer a molecular explanation for the hormonal control of gluconeogenesis. Glucose caused an inhibition of gluconeogenesis with no corresponding change in pyruvate kinase activity."} {"id": "PMID:183210", "title": "The endoplasmic reticulum: a cytochemist's view (a review).", "content": "Enzyme cytochemistry has been used, at the light and electron microscope levels, to \"mark\" cytoplasmic organelles of mammalian cells. Catalase cytochemistry permitted identification of microperoxisomes, apparently ubiquitous organelles that are attached by numerous slender connections to the endoplasmic reticulum. Thiamine pyrophosphatase and acid phosphatase cytochemistry can be used to distinguish between the Golgi apparatus and a specialized acid-phosphatase-rich region of smooth endoplasmic reticulum (ER) that appears to be involved in: (a) the formation of lysosomes and melanin granules: (b) the processing and packaging of secretory materials in endocrine and exocrine cells; and (c) the metabolism of lipid. The acronym GERL has been given to this region of smooth ER because it is located at the inner or \"trans\" aspect of the Golgi apparatus and because it appears to produce various types of Lysosomes.", "contents": "The endoplasmic reticulum: a cytochemist's view (a review). Enzyme cytochemistry has been used, at the light and electron microscope levels, to \"mark\" cytoplasmic organelles of mammalian cells. Catalase cytochemistry permitted identification of microperoxisomes, apparently ubiquitous organelles that are attached by numerous slender connections to the endoplasmic reticulum. Thiamine pyrophosphatase and acid phosphatase cytochemistry can be used to distinguish between the Golgi apparatus and a specialized acid-phosphatase-rich region of smooth endoplasmic reticulum (ER) that appears to be involved in: (a) the formation of lysosomes and melanin granules: (b) the processing and packaging of secretory materials in endocrine and exocrine cells; and (c) the metabolism of lipid. The acronym GERL has been given to this region of smooth ER because it is located at the inner or \"trans\" aspect of the Golgi apparatus and because it appears to produce various types of Lysosomes."} {"id": "PMID:183211", "title": "Transfer of tRNAs to somatic cells mediated by Sendai-virus-induced fusion.", "content": "tRNAs from yeast (tRNAPhe and 4S RNA) and Escherichia coli (suIII+ tRNAITyr) have been transferred to mouse cells by means of a two-step transfer procedure [Loyter, Zakai, and Kulka (1975) J. Cell Biol. 66, 292-304; Schlegel and Rechsteiner (1975) Cell 5, 371-379]. In the first stage of the transfer tRNAs were incorporated into rabbit red blood cells (RBCs). Thereafter, the loaded erythrocytes were fused with recipient mouse cells by means of Sendai virus. At least 0.3-0.4% of the total input of tRNA used to load the RBCs could be transferred to mouse cells. Of the tRNA incorporated in the mouse cells, at least 50% could be recovered in the form of intact tRNA molecules when yeast 4S RNA was used. With E. coli suIII+ tRNAITyr a rather smaller proportion of the tRNA remained intact (33%). Although the loading of tRNA into RBCs is not essential for its uptake, we find that the transfer is four times more efficient with RBCs as a vehicle for the injection. Significantly, a fraction (2%) of the recipient cells possessed much more incorporated tRNA than the average cell when Sendai virus and loaded RBCs were used. Such cells were not found in control experiments in which tRNA uptake was induced by Sendai virus alone.", "contents": "Transfer of tRNAs to somatic cells mediated by Sendai-virus-induced fusion. tRNAs from yeast (tRNAPhe and 4S RNA) and Escherichia coli (suIII+ tRNAITyr) have been transferred to mouse cells by means of a two-step transfer procedure [Loyter, Zakai, and Kulka (1975) J. Cell Biol. 66, 292-304; Schlegel and Rechsteiner (1975) Cell 5, 371-379]. In the first stage of the transfer tRNAs were incorporated into rabbit red blood cells (RBCs). Thereafter, the loaded erythrocytes were fused with recipient mouse cells by means of Sendai virus. At least 0.3-0.4% of the total input of tRNA used to load the RBCs could be transferred to mouse cells. Of the tRNA incorporated in the mouse cells, at least 50% could be recovered in the form of intact tRNA molecules when yeast 4S RNA was used. With E. coli suIII+ tRNAITyr a rather smaller proportion of the tRNA remained intact (33%). Although the loading of tRNA into RBCs is not essential for its uptake, we find that the transfer is four times more efficient with RBCs as a vehicle for the injection. Significantly, a fraction (2%) of the recipient cells possessed much more incorporated tRNA than the average cell when Sendai virus and loaded RBCs were used. Such cells were not found in control experiments in which tRNA uptake was induced by Sendai virus alone."} {"id": "PMID:183212", "title": "Vitamin K-dependent synthesis and modification of precursor prothrombin in cultured H-35 hepatoma cells.", "content": "The ability of confluent monolayers of H-35 cells, originally obtained from a rat hepatoma, to synthesize prothrombin in response to vitamin K1 (phylloquinone) was studied. As demonstrated by radioimmunoassay, selective barium salt adsorption, and two coagulation assays which discriminate between precursor- and mature-prothrombin, these cells retained their ability to synthesize precursor prothrombin (preprothrombin) in the absence of exogenous phylloquinone (vitamin K). When phylloquinone was added to the medium (100 ng/ml), the existing intracellular concentration of preprothrombin was reduced to 50% within 1 hr after exposure to the vitamin and slowly declined thereafter to approximately 30% of control levels by 36 hr. Concomitant with the rapid loss of intracellular preprothrombin was the appearance of mature prothrombin in the medium. The appearance of prothrombin was biphasic: occurring during the initial 0-6 hr interval, and again at an increased rate during the next 18-24 hr interval. The amount of prothrombin appearing in the medium exceeded by severalfold the amount of precursor mobilized. These data demonstrate that monolayer cultures of H-35 hepatoma cells retain their ability to synthesize preprothrombin and other enzymes, responsible for post-translational modification of prothrombin and its subsequent secretion, under the influence of vitamin K.", "contents": "Vitamin K-dependent synthesis and modification of precursor prothrombin in cultured H-35 hepatoma cells. The ability of confluent monolayers of H-35 cells, originally obtained from a rat hepatoma, to synthesize prothrombin in response to vitamin K1 (phylloquinone) was studied. As demonstrated by radioimmunoassay, selective barium salt adsorption, and two coagulation assays which discriminate between precursor- and mature-prothrombin, these cells retained their ability to synthesize precursor prothrombin (preprothrombin) in the absence of exogenous phylloquinone (vitamin K). When phylloquinone was added to the medium (100 ng/ml), the existing intracellular concentration of preprothrombin was reduced to 50% within 1 hr after exposure to the vitamin and slowly declined thereafter to approximately 30% of control levels by 36 hr. Concomitant with the rapid loss of intracellular preprothrombin was the appearance of mature prothrombin in the medium. The appearance of prothrombin was biphasic: occurring during the initial 0-6 hr interval, and again at an increased rate during the next 18-24 hr interval. The amount of prothrombin appearing in the medium exceeded by severalfold the amount of precursor mobilized. These data demonstrate that monolayer cultures of H-35 hepatoma cells retain their ability to synthesize preprothrombin and other enzymes, responsible for post-translational modification of prothrombin and its subsequent secretion, under the influence of vitamin K."} {"id": "PMID:183213", "title": "Freeze-fracture study of mast cell secretion.", "content": "Within seconds after exposure of rat peritoneal mast cells to polymyxin B, bulges appear on the surface of the cells. Freeze-fracture electron microscopy reveals that each bulge overlies a mast cell granule. In contrast to the even distribution of intramembranous particles in the plasma membrane of unstimulated cells, the intramembranous particles in the stimulated cells are unevenly distributed in the membrane of the bulges with large patches of membrane lacking intramembranous particles. The membranes over the most prominent bulges are entirely free of intramembranous particles, and in some instances there is an increased concentration of intramembranous particles at the margins of the bulges. Perigranule membranes exhibit the same changes in distribution of intramembranous particles. Electron microscopy of thin sections of rapidly fixed, stimulated mast cells shows a peculiar structure of the membrane overlying some bulges; instead of the pentalaminar membranes previously demonstrated, the membrane at these sites of presumptive fusion of perigranule and plasma membrane assumes the form of a single dense lamina with a fine fuzzy coating on either side. It seems possible that membrane fusion and subsequent pore formation proceed in the stimulated mast cell through a stage of flight of intramembranous particles and molecular rearrangement of the other membrane components.", "contents": "Freeze-fracture study of mast cell secretion. Within seconds after exposure of rat peritoneal mast cells to polymyxin B, bulges appear on the surface of the cells. Freeze-fracture electron microscopy reveals that each bulge overlies a mast cell granule. In contrast to the even distribution of intramembranous particles in the plasma membrane of unstimulated cells, the intramembranous particles in the stimulated cells are unevenly distributed in the membrane of the bulges with large patches of membrane lacking intramembranous particles. The membranes over the most prominent bulges are entirely free of intramembranous particles, and in some instances there is an increased concentration of intramembranous particles at the margins of the bulges. Perigranule membranes exhibit the same changes in distribution of intramembranous particles. Electron microscopy of thin sections of rapidly fixed, stimulated mast cells shows a peculiar structure of the membrane overlying some bulges; instead of the pentalaminar membranes previously demonstrated, the membrane at these sites of presumptive fusion of perigranule and plasma membrane assumes the form of a single dense lamina with a fine fuzzy coating on either side. It seems possible that membrane fusion and subsequent pore formation proceed in the stimulated mast cell through a stage of flight of intramembranous particles and molecular rearrangement of the other membrane components."} {"id": "PMID:183214", "title": "Abnormal levels of 3':5'-cyclic AMP in isoproterenol-stimulated fibroblasts from patients with cystic fibrosis.", "content": "To determine if the abnormalities of exocrine secretion characteristic of cystic fibrosis could be investigated in vitro, I studied the synthesis of 3':5'-cyclic AMP after isoproterenol stimulation in skin fibroblasts derived from patients with cystic fibrosis and from normal individuals. Comparison of normal and cystic fibrosis cells showed that the latter had 2- to 5-fold greater levels of intracellular cyclic AMP after stimulation with isoproterenol. The difference between the strains was observed at every stage of the culture cycle and was specific to stimulation by beta-adrenergic agonists. It could not be accounted for by different dose- or time-response curves nor by leakage of cyclic AMP into the medium. The increased sensitivity to catecholamines may reflect an intrinsic genetic property of cystic fibrosis cells, and it may be feasible to use this system to study the biochemical basis of the genetic defect in cystic fibrosis.", "contents": "Abnormal levels of 3':5'-cyclic AMP in isoproterenol-stimulated fibroblasts from patients with cystic fibrosis. To determine if the abnormalities of exocrine secretion characteristic of cystic fibrosis could be investigated in vitro, I studied the synthesis of 3':5'-cyclic AMP after isoproterenol stimulation in skin fibroblasts derived from patients with cystic fibrosis and from normal individuals. Comparison of normal and cystic fibrosis cells showed that the latter had 2- to 5-fold greater levels of intracellular cyclic AMP after stimulation with isoproterenol. The difference between the strains was observed at every stage of the culture cycle and was specific to stimulation by beta-adrenergic agonists. It could not be accounted for by different dose- or time-response curves nor by leakage of cyclic AMP into the medium. The increased sensitivity to catecholamines may reflect an intrinsic genetic property of cystic fibrosis cells, and it may be feasible to use this system to study the biochemical basis of the genetic defect in cystic fibrosis."} {"id": "PMID:183215", "title": "Presynaptic calcium currents and their relation to synaptic transmission: voltage clamp study in squid giant synapse and theoretical model for the calcium gate.", "content": "A voltage clamp study of the presynaptic terminal in squid stellate ganglion has given quantitative results relating inward Ca2+ current to presynaptic membrane potential and postsynaptic response to inward Ca2+ current. The results indicate an S-shaped curve for the relationship between presynaptic potential and Ca2+ current and a linear relationship between Ca2+ current and postsynaptic potential. A similar S-shaped curve was found for the time-dependent properties of the Ca2+ conductance. Based on these results a mathematical model was developed which accounts for the experimental results in this and previously published papers by other authors. The model suggests that five subunits are involved in the Ca2+ gate and that the subunits change noncooperatively from an inactive to an active form upon membrane depolarization.", "contents": "Presynaptic calcium currents and their relation to synaptic transmission: voltage clamp study in squid giant synapse and theoretical model for the calcium gate. A voltage clamp study of the presynaptic terminal in squid stellate ganglion has given quantitative results relating inward Ca2+ current to presynaptic membrane potential and postsynaptic response to inward Ca2+ current. The results indicate an S-shaped curve for the relationship between presynaptic potential and Ca2+ current and a linear relationship between Ca2+ current and postsynaptic potential. A similar S-shaped curve was found for the time-dependent properties of the Ca2+ conductance. Based on these results a mathematical model was developed which accounts for the experimental results in this and previously published papers by other authors. The model suggests that five subunits are involved in the Ca2+ gate and that the subunits change noncooperatively from an inactive to an active form upon membrane depolarization."} {"id": "PMID:183216", "title": "Localization and specificity of binding of subprimate placental lactogen in rabbit tissues.", "content": "A search for specific placental lactogen binding was undertaken in tissues obtained from late pregnant rabbits using the placental lactogens from sheep, cows, and human beings. 125I-labeled ovine lactogen exhibited highest specific binding to the adrenal gland (57.8%), followed by liver (21.5%), ovary (19.9%), mammary gland (15.9%), uterus (12.2%), kidney (8.8%), brain (8.5%), and adipose tissue (7.9%). In liver and mammary gland, the displacement curves for ovine and human lactogen were identical to that for bovine prolactin, indicating that they share the same receptor site. Although the displacement curve for bovine lactogen was parallel to that of the other lactogens the bovine hormone is less active in the radioreceptor assay.", "contents": "Localization and specificity of binding of subprimate placental lactogen in rabbit tissues. A search for specific placental lactogen binding was undertaken in tissues obtained from late pregnant rabbits using the placental lactogens from sheep, cows, and human beings. 125I-labeled ovine lactogen exhibited highest specific binding to the adrenal gland (57.8%), followed by liver (21.5%), ovary (19.9%), mammary gland (15.9%), uterus (12.2%), kidney (8.8%), brain (8.5%), and adipose tissue (7.9%). In liver and mammary gland, the displacement curves for ovine and human lactogen were identical to that for bovine prolactin, indicating that they share the same receptor site. Although the displacement curve for bovine lactogen was parallel to that of the other lactogens the bovine hormone is less active in the radioreceptor assay."} {"id": "PMID:183220", "title": "The effect of some additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate and milk.", "content": "The effect of various additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate or milk was investigated. Adsorption-elution, dialysis and sedimentation volume measurements were used in the present investigation. Citric acid was found to exert the highest adsorption suppressing effect of the antibiotic on both antacids. The nonionic surfactants, polyoxyethylene-23-lauryl ether (Brij 35) and polysorbate 80, had an intermediate action, while polyethylene glycol 6000 (PEG-6000), polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC) and urea had only a slight effect. On the other hand, the effect of sodium benzoate and sodium salicylate varied with concentration. Results of the elution study showed that the efficiency of the additives, as eluting agents, was more or less parallel with their influence on adsorption. The presence of citrate or Brij 35, having the highest adsorption-suppressing effect, was found to have a negligible effect on the chemical stability or microbiological activity of tetracycline. Conclusions were made that the incorporation of some of these additives may possibly reduce tetracycline-antacids interactions and consequently improve the antibiotic availability when co-administered with antacids.", "contents": "The effect of some additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate and milk. The effect of various additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate or milk was investigated. Adsorption-elution, dialysis and sedimentation volume measurements were used in the present investigation. Citric acid was found to exert the highest adsorption suppressing effect of the antibiotic on both antacids. The nonionic surfactants, polyoxyethylene-23-lauryl ether (Brij 35) and polysorbate 80, had an intermediate action, while polyethylene glycol 6000 (PEG-6000), polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC) and urea had only a slight effect. On the other hand, the effect of sodium benzoate and sodium salicylate varied with concentration. Results of the elution study showed that the efficiency of the additives, as eluting agents, was more or less parallel with their influence on adsorption. The presence of citrate or Brij 35, having the highest adsorption-suppressing effect, was found to have a negligible effect on the chemical stability or microbiological activity of tetracycline. Conclusions were made that the incorporation of some of these additives may possibly reduce tetracycline-antacids interactions and consequently improve the antibiotic availability when co-administered with antacids."} {"id": "PMID:183223", "title": "Serum sialic acid levels in lung cancer patients.", "content": "The levels of N-acetyl neuraminic acid (sialic acid) in normal men and pre-and post-menopausal women were determined. Smoking post-menopausal estrogen therapy, oral contraceptives, and refreezing had no effects on sialic acid levels. Pre-treatment values from patients with lung carcinoma showed markedly elevated levels of sialic acid (0.697 +/- 0.149 muM/ml) as compared to those from normal controls (0.432 +/- 0.067 muM/ml). The potential usefulness of sialic acid as a biological marker is discussed.", "contents": "Serum sialic acid levels in lung cancer patients. The levels of N-acetyl neuraminic acid (sialic acid) in normal men and pre-and post-menopausal women were determined. Smoking post-menopausal estrogen therapy, oral contraceptives, and refreezing had no effects on sialic acid levels. Pre-treatment values from patients with lung carcinoma showed markedly elevated levels of sialic acid (0.697 +/- 0.149 muM/ml) as compared to those from normal controls (0.432 +/- 0.067 muM/ml). The potential usefulness of sialic acid as a biological marker is discussed."} {"id": "PMID:183224", "title": "Biochemical changes after hepatic injury from toxic doses of acetaminophen or furosemide.", "content": "The effects of hepatotoxic doses of acetaminophen and furosemide on the function and composition of hepatic endoplasmic reticulum were compared from 3 to 24 h after administration. Acetaminophen caused a significant decrease in microsomal protein concentration as early as 3 h after its administration, but furosemide did not affect the microsomal protein concentration until 24 h after the dose. Both acetaminophen and furosemide decreased the concentrations of cytochrome P-450 and cytochrome b5 in microsomes, and the activity of microsomal ethylmorphine N-demethylase and aniline hydroxylase. Glucose-6-phosphatase and UDP-glucuronyl transferase were not significantly affected by acetaminophen or furosemide administration, and neither diene conjugation nor hepatic triglycerides were increased. Incorporation of 3H-L-leucine into liver proteins was decreased by 50% after the administration of either acetaminophen or furosemide.", "contents": "Biochemical changes after hepatic injury from toxic doses of acetaminophen or furosemide. The effects of hepatotoxic doses of acetaminophen and furosemide on the function and composition of hepatic endoplasmic reticulum were compared from 3 to 24 h after administration. Acetaminophen caused a significant decrease in microsomal protein concentration as early as 3 h after its administration, but furosemide did not affect the microsomal protein concentration until 24 h after the dose. Both acetaminophen and furosemide decreased the concentrations of cytochrome P-450 and cytochrome b5 in microsomes, and the activity of microsomal ethylmorphine N-demethylase and aniline hydroxylase. Glucose-6-phosphatase and UDP-glucuronyl transferase were not significantly affected by acetaminophen or furosemide administration, and neither diene conjugation nor hepatic triglycerides were increased. Incorporation of 3H-L-leucine into liver proteins was decreased by 50% after the administration of either acetaminophen or furosemide."} {"id": "PMID:183225", "title": "Quantitative analysis of the distribution of 3H-leucine in acid soluble chromatin proteins of Noviknoff hepatoma cells separated by two-dimensional polyacrylamide gel electrophoresis.", "content": "The acid soluble proteins of Novikoff hepatoma chromatin were labeled linearly with 3H-leucine for 16 minutes. Analysis on two-dimensional polyacrylamide gels showed that 13 of the 18 stained proteins were detected by autoradiography after a 16-minute in vitro incubation. The labeled molecules include the histones H2A, H2B, H3, and H4; and proteins A3, Aj, A8, A8', A15, A16, A24, B7, and B13. Relatively large amounts of isotope were incorporated into two other proteins, A3 and Aj, in addition to the histones. Some proteins, notably Aj, A8, A8' and A16 were labeled to a greater extent than would be expected on the basis of uptake of Coomassie Brilliant Blue R. None of the labeling patterns were characteristic of a precursor-product relationship either the histones or the nonhistone proteins.", "contents": "Quantitative analysis of the distribution of 3H-leucine in acid soluble chromatin proteins of Noviknoff hepatoma cells separated by two-dimensional polyacrylamide gel electrophoresis. The acid soluble proteins of Novikoff hepatoma chromatin were labeled linearly with 3H-leucine for 16 minutes. Analysis on two-dimensional polyacrylamide gels showed that 13 of the 18 stained proteins were detected by autoradiography after a 16-minute in vitro incubation. The labeled molecules include the histones H2A, H2B, H3, and H4; and proteins A3, Aj, A8, A8', A15, A16, A24, B7, and B13. Relatively large amounts of isotope were incorporated into two other proteins, A3 and Aj, in addition to the histones. Some proteins, notably Aj, A8, A8' and A16 were labeled to a greater extent than would be expected on the basis of uptake of Coomassie Brilliant Blue R. None of the labeling patterns were characteristic of a precursor-product relationship either the histones or the nonhistone proteins."} {"id": "PMID:183226", "title": "Influence of size, protein concentration, protein synthesis inhibitors,and carbon on clearance of enzymes and proteins from blood.", "content": "In order to (1) clarify the mechanism(s) for clearance and maintenance of protein levels from and in extracellular fluids, and (2) explore the possibility of interconnections between enzyme plasma levels and those of tissues, rats were injected with glutamate dehydrogenase, phosphoglycerate, encolase, carbamyl phosphate synthetase, serine dehydratase, deoxyribonuclease I, ribonuclease A, hemoglobin, and human serum albumin. A close relationship between the molecular weights of enzymes and the rates of clearance was found.", "contents": "Influence of size, protein concentration, protein synthesis inhibitors,and carbon on clearance of enzymes and proteins from blood. In order to (1) clarify the mechanism(s) for clearance and maintenance of protein levels from and in extracellular fluids, and (2) explore the possibility of interconnections between enzyme plasma levels and those of tissues, rats were injected with glutamate dehydrogenase, phosphoglycerate, encolase, carbamyl phosphate synthetase, serine dehydratase, deoxyribonuclease I, ribonuclease A, hemoglobin, and human serum albumin. A close relationship between the molecular weights of enzymes and the rates of clearance was found."} {"id": "PMID:183228", "title": "[Determination of the variation in conduction speed of motor fibers and the effects of diphenylhydantoin (Phenytoin) and diazepam (Faustan)].", "content": "The variation in the speed of conduction of motor fibers of the ulnar nerve was determined by Hopf's double-stimulus method and compared with values obtained from the duration of muscular response potentials for differently spaced points of stimulation. However, the values obtained from the difference of the duration of response potentials are inadequate since the duration of potentials cannot always be determined accurately. After a ten-day administration of faustan (15 mg per day) or phenytoin (300 mg per day) there was observed a decrease especially in the minimum rate of conduction of motor fibers of the ulnar nerve.", "contents": "[Determination of the variation in conduction speed of motor fibers and the effects of diphenylhydantoin (Phenytoin) and diazepam (Faustan)]. The variation in the speed of conduction of motor fibers of the ulnar nerve was determined by Hopf's double-stimulus method and compared with values obtained from the duration of muscular response potentials for differently spaced points of stimulation. However, the values obtained from the difference of the duration of response potentials are inadequate since the duration of potentials cannot always be determined accurately. After a ten-day administration of faustan (15 mg per day) or phenytoin (300 mg per day) there was observed a decrease especially in the minimum rate of conduction of motor fibers of the ulnar nerve."} {"id": "PMID:183230", "title": "Plasma lipoproteins of lambs and sheep.", "content": "The major plasma lipoproteins of the adult sheep were high density lipoprotein (76%) having alpha-mobility on electrophoresis and low density lipoprotein (20%) having beta-mobility. Chylomicrons and very low density lipoproteins were minor constituents (less than 5%). The postabsorptive hyperlipidaemia in suckling lambs is mainly a result of increased concentration of low density and high density lipoproteins although the relative contribution of very low density lipoproteins was increased to 7-15% of the total lipoproteins. The hyperlipiaemia was markedly greater in an intact male lamb than in female or castrated male lambs. In suckling lambs a new lipoprotein (density 1-090 g/ml) appeared in the high density lipoprotein fraction but disappeared before weaning.", "contents": "Plasma lipoproteins of lambs and sheep. The major plasma lipoproteins of the adult sheep were high density lipoprotein (76%) having alpha-mobility on electrophoresis and low density lipoprotein (20%) having beta-mobility. Chylomicrons and very low density lipoproteins were minor constituents (less than 5%). The postabsorptive hyperlipidaemia in suckling lambs is mainly a result of increased concentration of low density and high density lipoproteins although the relative contribution of very low density lipoproteins was increased to 7-15% of the total lipoproteins. The hyperlipiaemia was markedly greater in an intact male lamb than in female or castrated male lambs. In suckling lambs a new lipoprotein (density 1-090 g/ml) appeared in the high density lipoprotein fraction but disappeared before weaning."} {"id": "PMID:183234", "title": "Photolysis of N-methyl and N-acetyl substituted amino acids.", "content": "Experiments on the production of free radicals in aqueous solutions of N-methyl and N-acetyl substituted amino acids by UV light are reported. The ESR spectra observed at 77 K show that the bond of the CH3- group of these substances is ruptured to a great deal compared with other bond ruptures producing paramagnetic centres. But in N-methyl substituted amino acids the methyl radical is less predominant than in N-acetyl substituted ones. At temperatures higher than 200 K the ESR spectra of all substances studied in our experiments are similar. It is supposed that a radical is formed with an unpaired spin near an oxygen atom.", "contents": "Photolysis of N-methyl and N-acetyl substituted amino acids. Experiments on the production of free radicals in aqueous solutions of N-methyl and N-acetyl substituted amino acids by UV light are reported. The ESR spectra observed at 77 K show that the bond of the CH3- group of these substances is ruptured to a great deal compared with other bond ruptures producing paramagnetic centres. But in N-methyl substituted amino acids the methyl radical is less predominant than in N-acetyl substituted ones. At temperatures higher than 200 K the ESR spectra of all substances studied in our experiments are similar. It is supposed that a radical is formed with an unpaired spin near an oxygen atom."} {"id": "PMID:183235", "title": "The action of ionizing radiation on DNA in the presence of quinacrine. III. E.S.R. study: spin transfer in gamma-irradiated lyophilized DNA-quinacrine complexes.", "content": "E.S.R. spectra of different DNA-quinacrine complexes show as well at 77 K as at 293 K that there exists an electron transfer from the bases to quinacrine facilitated by the overlap of the theta-orbitals of the bases and the intercalated dye. The transfer range may extend over more than 25 or 50 nucleotides depending on the intercalation model considered.", "contents": "The action of ionizing radiation on DNA in the presence of quinacrine. III. E.S.R. study: spin transfer in gamma-irradiated lyophilized DNA-quinacrine complexes. E.S.R. spectra of different DNA-quinacrine complexes show as well at 77 K as at 293 K that there exists an electron transfer from the bases to quinacrine facilitated by the overlap of the theta-orbitals of the bases and the intercalated dye. The transfer range may extend over more than 25 or 50 nucleotides depending on the intercalation model considered."} {"id": "PMID:183237", "title": "Effect of Indomethacin on cyclic AMP phosphodiesterase activity in myometrium from pregnant rhesus monkeys.", "content": "Our results indicate that indomethacin inhibits cyclic AMP phosphodiesterase in the myometrium of the pregnant rhesus monkey under in vitro as well as in vivo conditions. Kinetic data on extracts of myometrium from pregnant rhesus monkeys indicated two cyclic AMP phosphodiesterase activities. The apparent Km value for the high affinity enzyme averaged 3.9 muM and for the low affinity enzyme 23 muM; the Vmax values averaged 0.56 and 1.4 nmoles cyclic AMP hydrolized per mg protein min-1 respectively. When indomethacin was added to the myometrial extracts, the activity of the high Km phosphodiesterase was competitively inhibited, with an average Ki of 200 muM; the low Km enzyme was noncompetitively inhibited with an average Ki of 110 muM. Experiments on myometrial slices demonstrated that 10 muM indomethsacin potentiated the effect of PGE1 and epinephrine on cyclic AMP levels, presumably by inhibiting the phophodiesterase activity. The uterine relaxing effect of indomethacin is generally attributed to the inhibition of prostaglandin synthetase activity. However, treatment of pregnant rhesus monkeys with therapeutic doses of indomethacin resulted in a significant inhibition of myometrial cyclic AMP phosphodiesterase activity in association with uterine relaxation and prolongation of gestation.", "contents": "Effect of Indomethacin on cyclic AMP phosphodiesterase activity in myometrium from pregnant rhesus monkeys. Our results indicate that indomethacin inhibits cyclic AMP phosphodiesterase in the myometrium of the pregnant rhesus monkey under in vitro as well as in vivo conditions. Kinetic data on extracts of myometrium from pregnant rhesus monkeys indicated two cyclic AMP phosphodiesterase activities. The apparent Km value for the high affinity enzyme averaged 3.9 muM and for the low affinity enzyme 23 muM; the Vmax values averaged 0.56 and 1.4 nmoles cyclic AMP hydrolized per mg protein min-1 respectively. When indomethacin was added to the myometrial extracts, the activity of the high Km phosphodiesterase was competitively inhibited, with an average Ki of 200 muM; the low Km enzyme was noncompetitively inhibited with an average Ki of 110 muM. Experiments on myometrial slices demonstrated that 10 muM indomethsacin potentiated the effect of PGE1 and epinephrine on cyclic AMP levels, presumably by inhibiting the phophodiesterase activity. The uterine relaxing effect of indomethacin is generally attributed to the inhibition of prostaglandin synthetase activity. However, treatment of pregnant rhesus monkeys with therapeutic doses of indomethacin resulted in a significant inhibition of myometrial cyclic AMP phosphodiesterase activity in association with uterine relaxation and prolongation of gestation."} {"id": "PMID:183238", "title": "Radioimmunoassay measurement of ACTH-facilitated PGE2 and PGF2alpha release from isolated cat adrenocortical cells.", "content": "Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF2alpha and PGF1alpha antisera established that PGF2alpha is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH4) these same two antisera were also used to identify PGE2 as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50-250muU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH.", "contents": "Radioimmunoassay measurement of ACTH-facilitated PGE2 and PGF2alpha release from isolated cat adrenocortical cells. Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF2alpha and PGF1alpha antisera established that PGF2alpha is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH4) these same two antisera were also used to identify PGE2 as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50-250muU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH."} {"id": "PMID:183240", "title": "Phospholipase A activity in human and ovine uterine tissues.", "content": "Phospholipase A was assayed in crude lysosomal fractions of human decidua, amnion, chorion and myometrium. Activity was present in all the tissues and was highest in decidua and amnion which contained enzymes with pH optima of 6.5-8.0 and 7.2 respectively. Comparison of the activities in tissues obtained before labor with others obtained during labor showed no differences. In sheep, the fetal membranes contained a greater activity of phospholipase A than placenta and myometrium. Stimulation of the fetal adrenals with corticotrophin caused a marked increase in activity in both amnion and chorioallantois. It is concluded that the human amnion and the ovine amnion and chorioallantois could participate in the biosynthesis of prostaglandins by releasing stored arachidonic acid.", "contents": "Phospholipase A activity in human and ovine uterine tissues. Phospholipase A was assayed in crude lysosomal fractions of human decidua, amnion, chorion and myometrium. Activity was present in all the tissues and was highest in decidua and amnion which contained enzymes with pH optima of 6.5-8.0 and 7.2 respectively. Comparison of the activities in tissues obtained before labor with others obtained during labor showed no differences. In sheep, the fetal membranes contained a greater activity of phospholipase A than placenta and myometrium. Stimulation of the fetal adrenals with corticotrophin caused a marked increase in activity in both amnion and chorioallantois. It is concluded that the human amnion and the ovine amnion and chorioallantois could participate in the biosynthesis of prostaglandins by releasing stored arachidonic acid."} {"id": "PMID:183241", "title": "The role of prostaglandins in the development of refractoriness to LH stimulation by Graafian follicles.", "content": "The possibility that prostaglandins might be responsible for the development of the pre-ovulatory refractoriness to the stimulation by LH of cyclic AMP accumulation in vitro in the Graafian follicle was examined. Isolated rabbit Graafian follicles were obtained at estrus and at 0.5, 5 and 9 hours after an ovulatory dose of LH. The follicles were incubated in vitro in the presence of (8-3H)adenine and the accumulation of (8-3H)cyclic AMP measured. Follicles from estrous animals responded to the in vitro addition of LH with a marked increase of cyclic AMP accumulation and lost this response as the time of ovulation approached. Animals pretreated with indomethacin, which inhibits the usual pre-ovulatory rise of follicular prostaglandin levels, showed essentially the same loss of responsiveness. Indomethacin alone was without effect. It is concluded that prostaglandins are not the major factor in the development of refractoriness to LH stimulation in vitro which has been observed in pre-ovulatory follicles.", "contents": "The role of prostaglandins in the development of refractoriness to LH stimulation by Graafian follicles. The possibility that prostaglandins might be responsible for the development of the pre-ovulatory refractoriness to the stimulation by LH of cyclic AMP accumulation in vitro in the Graafian follicle was examined. Isolated rabbit Graafian follicles were obtained at estrus and at 0.5, 5 and 9 hours after an ovulatory dose of LH. The follicles were incubated in vitro in the presence of (8-3H)adenine and the accumulation of (8-3H)cyclic AMP measured. Follicles from estrous animals responded to the in vitro addition of LH with a marked increase of cyclic AMP accumulation and lost this response as the time of ovulation approached. Animals pretreated with indomethacin, which inhibits the usual pre-ovulatory rise of follicular prostaglandin levels, showed essentially the same loss of responsiveness. Indomethacin alone was without effect. It is concluded that prostaglandins are not the major factor in the development of refractoriness to LH stimulation in vitro which has been observed in pre-ovulatory follicles."} {"id": "PMID:183252", "title": "On the absence of \"endogenous\" acetaldehyde in rat and mouse blood.", "content": "Acetaldehyde was not detected in whole blood or plasma of control Sprague-Dawley rats or rats treated with Antabuse, or in whole blood of control Swiss-Webster mice or mice treated with diethyldithiocarbamate.", "contents": "On the absence of \"endogenous\" acetaldehyde in rat and mouse blood. Acetaldehyde was not detected in whole blood or plasma of control Sprague-Dawley rats or rats treated with Antabuse, or in whole blood of control Swiss-Webster mice or mice treated with diethyldithiocarbamate."} {"id": "PMID:183253", "title": "Isolation of an SV40 induced sarcoma transformation associated antigen.", "content": "A transformation associated antigen was isolated from an SV40 induced hamster sarcoma by sequential silica gel column chromatography and preparative silica gel 60 thin layer chromatography after tissue extraction with chloroform:methanol (2:1, v/v). It migrated with an rf of 0.21 on silica gel 60 thin layer chromatography plates predeveloped and developed in chloroform:methanol:water:glacial acetic acid (10:10:1.5:0.5, v/v) and an rf of 0.27 on cellulose F254 thin layer chromatography plates developed in the same solvent system. Antigenicity was determined using a fluorescence probe cytotoxicity assay to measure inhibition of antibody mediated complement dependent damage to homologous cultured transformed cells. Although compositional analysis of this substance is not complete, it appears to be a polar lipid and would support the concept that transformation associated antigens may be gene plus substrate specific rather than strictly gene specific.", "contents": "Isolation of an SV40 induced sarcoma transformation associated antigen. A transformation associated antigen was isolated from an SV40 induced hamster sarcoma by sequential silica gel column chromatography and preparative silica gel 60 thin layer chromatography after tissue extraction with chloroform:methanol (2:1, v/v). It migrated with an rf of 0.21 on silica gel 60 thin layer chromatography plates predeveloped and developed in chloroform:methanol:water:glacial acetic acid (10:10:1.5:0.5, v/v) and an rf of 0.27 on cellulose F254 thin layer chromatography plates developed in the same solvent system. Antigenicity was determined using a fluorescence probe cytotoxicity assay to measure inhibition of antibody mediated complement dependent damage to homologous cultured transformed cells. Although compositional analysis of this substance is not complete, it appears to be a polar lipid and would support the concept that transformation associated antigens may be gene plus substrate specific rather than strictly gene specific."} {"id": "PMID:183254", "title": "Detection of estrogen binding in human mammary carcinoma by immunofluorescence: a new technic utilizing the binding hormone in a polymerized state.", "content": "Detection of neoplastic cells with the ability to bind estrogen has been accomplished utilizing the immunofluorescence technic and polymerized estradiol phosphate. Biopsies from 10 patients with the more common varieties of breast cancer have been studied and show excellent correlation with independently performed tritiated estradiol receptor assays. Preliminary results show that many mammary carcinomas are composed of heterogenous cell populations which vary in their estrogen binding capacities. To some extent, such variations are dependent upon the anatomical location of the malignant cells.", "contents": "Detection of estrogen binding in human mammary carcinoma by immunofluorescence: a new technic utilizing the binding hormone in a polymerized state. Detection of neoplastic cells with the ability to bind estrogen has been accomplished utilizing the immunofluorescence technic and polymerized estradiol phosphate. Biopsies from 10 patients with the more common varieties of breast cancer have been studied and show excellent correlation with independently performed tritiated estradiol receptor assays. Preliminary results show that many mammary carcinomas are composed of heterogenous cell populations which vary in their estrogen binding capacities. To some extent, such variations are dependent upon the anatomical location of the malignant cells."} {"id": "PMID:183259", "title": "[Production and characterization of some mouse embryo cellular substrates in vitro].", "content": "Cell cultures with a different multiplication potential in vitro, depending upon the strain source used, were obtained from mouse embryos belonging to the CVA, C57 Black A2G and Swiss strains. Only the Swiss 12 culture underwent spontaneous transformation and was carried through more than 50 passages in vitro. The Swiss-12 substrate proved not to be contaminated either by viruses or micoplasma. It is less sensitive than other elective cell substrates to infection with attenuated polioviruses, cytopathogenic Coxsackie A9 virus and vaccinia virus, but its sensitivity to infection with Herpes simplex type 1 virus is similar to that of human embryo fibroblasts. After a high number of passages the Swiss-12 substrate permits, in comparison to other cell substrates (human heteroploid Hep-2 line, human embryo fibroblasts), a highly efficient qualitative differentiation between the growth media and calf serum.", "contents": "[Production and characterization of some mouse embryo cellular substrates in vitro]. Cell cultures with a different multiplication potential in vitro, depending upon the strain source used, were obtained from mouse embryos belonging to the CVA, C57 Black A2G and Swiss strains. Only the Swiss 12 culture underwent spontaneous transformation and was carried through more than 50 passages in vitro. The Swiss-12 substrate proved not to be contaminated either by viruses or micoplasma. It is less sensitive than other elective cell substrates to infection with attenuated polioviruses, cytopathogenic Coxsackie A9 virus and vaccinia virus, but its sensitivity to infection with Herpes simplex type 1 virus is similar to that of human embryo fibroblasts. After a high number of passages the Swiss-12 substrate permits, in comparison to other cell substrates (human heteroploid Hep-2 line, human embryo fibroblasts), a highly efficient qualitative differentiation between the growth media and calf serum."} {"id": "PMID:183265", "title": "Localization of apolipoprotein B in intestinal epithelial cells.", "content": "Indirect immunofluorescence techniques were employed to determine the distribution within intestinal epithelial cells of apolipoprotein B, a protein essential for the normal transport of fat. Isolated intestinal cells were prepared from rats either during active lipid absorption or after biliary diversion. Specific immunofluorescence from an antiserum to apolipoprotein B was detected in the apical portion of epithelial cells from bile-diverted animals, demonstrating that a pool of apolipoprotein B is present in the nonabsorptive epithelial cell and may be a component of intestinal cell membranes. During lipid absorption in normal rats, an early and sustained increase in immunofluorescence was demonstrated, consistent with an increase synthesis of apolipoprotein B during lipid absorption. This study demonstrates the presence of apolipoprotein B within intestinal epithelium and provides evidence for the participation of this apoprotein in intestinal lipid transport.", "contents": "Localization of apolipoprotein B in intestinal epithelial cells. Indirect immunofluorescence techniques were employed to determine the distribution within intestinal epithelial cells of apolipoprotein B, a protein essential for the normal transport of fat. Isolated intestinal cells were prepared from rats either during active lipid absorption or after biliary diversion. Specific immunofluorescence from an antiserum to apolipoprotein B was detected in the apical portion of epithelial cells from bile-diverted animals, demonstrating that a pool of apolipoprotein B is present in the nonabsorptive epithelial cell and may be a component of intestinal cell membranes. During lipid absorption in normal rats, an early and sustained increase in immunofluorescence was demonstrated, consistent with an increase synthesis of apolipoprotein B during lipid absorption. This study demonstrates the presence of apolipoprotein B within intestinal epithelium and provides evidence for the participation of this apoprotein in intestinal lipid transport."} {"id": "PMID:183260", "title": "Spontaneous mutation of RNA tumour viruses.", "content": "There are 2 categories of spontaneously occurring avian and mammalian RNA tumour virus mutants: conditional and non-conditional. 1) Conditional mutants are able to replicate in or transform cells only under certain physiological conditions or in certain cells. RNA tumour virus temperature-sensitive mutants, focus-morphology mutants, and host range mutants are spontaneously formed. Some of these conditional mutants probably arise by point mutations in the viral genome. 2) Non-conditional mutants have genetic lesions that render them inactive under all conditions. There are non-conditional spontaneous RNA tumour virus mutants that are missing either the virion envelope glycoprotein or both the envelope glycoprotein and the virion DNA polymerase. These mutants cannot replicate or transform cells. Other spontaneous non-conditional mutants can replicate but are defective in their ability to transform fibroblastoid cells. These spontaneous transformation-defective mutants can have deletions in 10-20% of the genomic RNA. Conditional mutants with an altered host range occur at a high rate of approximately 1 mutation/50 infected cell generations during DNA-to-DNA information transfer. This type of conditional mutation requires cell replication but does not occur frequently either during the original synthesis of viral DNA (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the DNA (DNA-to-RNA information transfer). Temperature-sensitive and focus-morphology mutants also have a high rate of spontaneous formation. Non-conditional mutants missing the viral envelope glycoprotein, DNA polymerase, or transformation gene, also appear to be spontaneously formed at a high rate. Normal avian and mammalian cells contain RNA tumour virus-related genes in their DNA. It is hypothesized that these endogenous RNA tumour virus-related genes in normal cells also have a high rate of spontaneous mutation and are involved in neoplastic processes.", "contents": "Spontaneous mutation of RNA tumour viruses. There are 2 categories of spontaneously occurring avian and mammalian RNA tumour virus mutants: conditional and non-conditional. 1) Conditional mutants are able to replicate in or transform cells only under certain physiological conditions or in certain cells. RNA tumour virus temperature-sensitive mutants, focus-morphology mutants, and host range mutants are spontaneously formed. Some of these conditional mutants probably arise by point mutations in the viral genome. 2) Non-conditional mutants have genetic lesions that render them inactive under all conditions. There are non-conditional spontaneous RNA tumour virus mutants that are missing either the virion envelope glycoprotein or both the envelope glycoprotein and the virion DNA polymerase. These mutants cannot replicate or transform cells. Other spontaneous non-conditional mutants can replicate but are defective in their ability to transform fibroblastoid cells. These spontaneous transformation-defective mutants can have deletions in 10-20% of the genomic RNA. Conditional mutants with an altered host range occur at a high rate of approximately 1 mutation/50 infected cell generations during DNA-to-DNA information transfer. This type of conditional mutation requires cell replication but does not occur frequently either during the original synthesis of viral DNA (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the DNA (DNA-to-RNA information transfer). Temperature-sensitive and focus-morphology mutants also have a high rate of spontaneous formation. Non-conditional mutants missing the viral envelope glycoprotein, DNA polymerase, or transformation gene, also appear to be spontaneously formed at a high rate. Normal avian and mammalian cells contain RNA tumour virus-related genes in their DNA. It is hypothesized that these endogenous RNA tumour virus-related genes in normal cells also have a high rate of spontaneous mutation and are involved in neoplastic processes."} {"id": "PMID:183266", "title": "Cytokine inhibition of DNA synthesis: effect on cyclic adenosine monophosphate in lymphocytes.", "content": "A greater than twofold increase in intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibited DNA synthesis, in stimulated rat lymphocytes. A two- to fourfold rise of intracellular cyclic AMP, starting at 16 hours, was produced by purified inhibitor od DNA synthesis added to such cells either at 0 or 16 hours, in close association with the initiation of DNA synthesis.", "contents": "Cytokine inhibition of DNA synthesis: effect on cyclic adenosine monophosphate in lymphocytes. A greater than twofold increase in intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibited DNA synthesis, in stimulated rat lymphocytes. A two- to fourfold rise of intracellular cyclic AMP, starting at 16 hours, was produced by purified inhibitor od DNA synthesis added to such cells either at 0 or 16 hours, in close association with the initiation of DNA synthesis."} {"id": "PMID:183261", "title": "[The chemotherapy of tumors of the central nervous system (author's transl)].", "content": "The rational application of chemotherapy in tumors of the central nervous system is discussed in particular the use of the new derivatives of nitrosourea: BCNU (1-3 bis-(2-cloroetil) 1-nitrosourea) and CCNU (cloroetil-cicloesil-nitrosourea). The results of therapy with antimetabolites, alkylating agents, antibiotics, and plant alcaloids, are reported as well as those obtained with radio - sensitizing substances (containing B10 or BUdR, IUdR, FUdR). The results obtained in the United States and in Japan with BCNU and CCNU are considered as well as the personal data of 43 cases treated with BCNU and 10 cases treated with CCNU (including intracranial glial tumors, spinal glial tumors and metastatic tumors of the central nervous system).", "contents": "[The chemotherapy of tumors of the central nervous system (author's transl)]. The rational application of chemotherapy in tumors of the central nervous system is discussed in particular the use of the new derivatives of nitrosourea: BCNU (1-3 bis-(2-cloroetil) 1-nitrosourea) and CCNU (cloroetil-cicloesil-nitrosourea). The results of therapy with antimetabolites, alkylating agents, antibiotics, and plant alcaloids, are reported as well as those obtained with radio - sensitizing substances (containing B10 or BUdR, IUdR, FUdR). The results obtained in the United States and in Japan with BCNU and CCNU are considered as well as the personal data of 43 cases treated with BCNU and 10 cases treated with CCNU (including intracranial glial tumors, spinal glial tumors and metastatic tumors of the central nervous system)."} {"id": "PMID:183267", "title": "Progesterone binding to hen oviduct genome: specific versus nonspecific binding.", "content": "Data are presented to explain discrepancies in the literature involving the in vitro binding of steroid receptor complexes to isolated nuclei and chromatin. The type of binding in vitro of the progesterone-receptor complex to nuclei, chromatin, or DNA of hen organs is largely determined by the ionic strength of the medium. Low ionic conditions (0.01 to 0.05 molar potassium chloride) result in a nonspecific, nonsaturable binding, while high ionic conditions (0.15 to 0.20 molar potassium chloride) create a tissue-specific, saturable binding. Pure DNA binds the steroid receptor complex extensively in low salt but very little in the higher salt conditions.", "contents": "Progesterone binding to hen oviduct genome: specific versus nonspecific binding. Data are presented to explain discrepancies in the literature involving the in vitro binding of steroid receptor complexes to isolated nuclei and chromatin. The type of binding in vitro of the progesterone-receptor complex to nuclei, chromatin, or DNA of hen organs is largely determined by the ionic strength of the medium. Low ionic conditions (0.01 to 0.05 molar potassium chloride) result in a nonspecific, nonsaturable binding, while high ionic conditions (0.15 to 0.20 molar potassium chloride) create a tissue-specific, saturable binding. Pure DNA binds the steroid receptor complex extensively in low salt but very little in the higher salt conditions."} {"id": "PMID:183268", "title": "Thyroid hormones: effect of physiological concentrations on cultured cardiac cells.", "content": "Cultured cardiac cells prepared from newborn rat heart will respond in vitro to physiological concentrations of L-triiodothyronine. The cells are grown in a culture medium that contains hypothyroid calf serum. A dose response relationship of L-triiodothyronine indicates that this system may be a useful model for elucidation of the mechanism of thyroid hormone effects on the heart.", "contents": "Thyroid hormones: effect of physiological concentrations on cultured cardiac cells. Cultured cardiac cells prepared from newborn rat heart will respond in vitro to physiological concentrations of L-triiodothyronine. The cells are grown in a culture medium that contains hypothyroid calf serum. A dose response relationship of L-triiodothyronine indicates that this system may be a useful model for elucidation of the mechanism of thyroid hormone effects on the heart."} {"id": "PMID:183270", "title": "[Prevention of infections in patients subjected to immunosuppressive drugs. Experience of a nephrologist].", "content": "Infective complications favoured by non-specific immuno-depression are common after renal transplantation. Often severe, they represent the main cause of mortality. Their prophylaxis is necessary at all stages of treatment. Before transplantation, the eradication of curable infective foci is essential, and certain patients must be excluded from the programme. The operation is simplified to a maximum. The conditioning is such that one does no longer expose to the risk of aplasia. These facts render useless the isolation of the patient on a sterile unit. In cases of poor tolerance of the transplant, with repeated rejection, the reduction and eventually the stopping of immunosuppression is necessary. This attitude implies often early return to treatment by repeated hemodialysis, but it preserves to a maximum the chances of a new transplantation.", "contents": "[Prevention of infections in patients subjected to immunosuppressive drugs. Experience of a nephrologist]. Infective complications favoured by non-specific immuno-depression are common after renal transplantation. Often severe, they represent the main cause of mortality. Their prophylaxis is necessary at all stages of treatment. Before transplantation, the eradication of curable infective foci is essential, and certain patients must be excluded from the programme. The operation is simplified to a maximum. The conditioning is such that one does no longer expose to the risk of aplasia. These facts render useless the isolation of the patient on a sterile unit. In cases of poor tolerance of the transplant, with repeated rejection, the reduction and eventually the stopping of immunosuppression is necessary. This attitude implies often early return to treatment by repeated hemodialysis, but it preserves to a maximum the chances of a new transplantation."} {"id": "PMID:183271", "title": "[Rejections and cytomegalovirus infections after renal transplantation].", "content": "Immunosuppressed patients are known to be susceptible to infectious agents. Association of allograft rejection and herpes virus infection (high incidence of cytomegalovirus) was yet reported after renal transplantation. Authors studied 19 rejection episodes on 24 renal transplantation performed for 17 months, cytomegalovirus infection being associated in 7. Because of the therapeutic difficulties observed in these cases, a preventive attitude is necessary.", "contents": "[Rejections and cytomegalovirus infections after renal transplantation]. Immunosuppressed patients are known to be susceptible to infectious agents. Association of allograft rejection and herpes virus infection (high incidence of cytomegalovirus) was yet reported after renal transplantation. Authors studied 19 rejection episodes on 24 renal transplantation performed for 17 months, cytomegalovirus infection being associated in 7. Because of the therapeutic difficulties observed in these cases, a preventive attitude is necessary."} {"id": "PMID:183272", "title": "[Infectious problems posed by patients with a renal graft and submitted to an immunosuppressive treatment].", "content": "Infective complications are analysed in 100 transplanted patients all receiving corticosteroid and azathioprine. 170 infective episodes were noted, only 13 patients never had infection during the period of observation. Two complications were dominated by their gravity : pneumopathies (n equals 29) fatal in 20.6% of cases, and septicemia (n equals 21) fatal in 28.5% of cases. Alone they represented 75% of the overall mortality in this series. More than 50% of failures due to death or detransplantation, were directly due to infection. The results show that this type of complication represents the main limiting factor to renal grafts in patients submitted to immunosuppressor treatment which depresses non-specifically, the whole immune response.", "contents": "[Infectious problems posed by patients with a renal graft and submitted to an immunosuppressive treatment]. Infective complications are analysed in 100 transplanted patients all receiving corticosteroid and azathioprine. 170 infective episodes were noted, only 13 patients never had infection during the period of observation. Two complications were dominated by their gravity : pneumopathies (n equals 29) fatal in 20.6% of cases, and septicemia (n equals 21) fatal in 28.5% of cases. Alone they represented 75% of the overall mortality in this series. More than 50% of failures due to death or detransplantation, were directly due to infection. The results show that this type of complication represents the main limiting factor to renal grafts in patients submitted to immunosuppressor treatment which depresses non-specifically, the whole immune response."} {"id": "PMID:183273", "title": "[Infections and immunosuppressive agents in rheumatology].", "content": "The authors review the problem of infection occurring in patients with chronic inflammatory rheumatism, e.g. rheumatoid arthritis, and lupus erythematosus, treated with cytolytic drugs for immunodepressive reasons. From their investigation, it seems that there is a high frequency of bacterial and mycotic and viral infections in these patients, but controlled investigations seem to show quite definitely that the frequency of these infections depends on the disease itself. The risk does not seem to be increased by cytolytic drugs. The only exception is herpes which appears in 10 to 20% of patients treated with immunosuppressive agents, as against 2% in a controll series. The other virus diseases did not have an abnormally high frequency. The conclusions are, of course, only of value for the types of treatment used in rheumatology.", "contents": "[Infections and immunosuppressive agents in rheumatology]. The authors review the problem of infection occurring in patients with chronic inflammatory rheumatism, e.g. rheumatoid arthritis, and lupus erythematosus, treated with cytolytic drugs for immunodepressive reasons. From their investigation, it seems that there is a high frequency of bacterial and mycotic and viral infections in these patients, but controlled investigations seem to show quite definitely that the frequency of these infections depends on the disease itself. The risk does not seem to be increased by cytolytic drugs. The only exception is herpes which appears in 10 to 20% of patients treated with immunosuppressive agents, as against 2% in a controll series. The other virus diseases did not have an abnormally high frequency. The conclusions are, of course, only of value for the types of treatment used in rheumatology."} {"id": "PMID:183274", "title": "[Fatal hyperparathyroidism].", "content": "Hyperparathyroidism is able to determine suddenly after a very poor clinical history a deep coma : in such a condition, the diagnosis with the paraneoplastic hypercalcemia may be a difficult one : cervicotomy can be the hero\u00efc way to lead to diagnosis and in the same time to perform treatment. To avoid such a dramatic situation, the authors propose cervicotomy for every patient suspected of P.T.H. adenoma, when calcemia is higher than 115 mg c/l, even if the symptoms are very slight or nil.", "contents": "[Fatal hyperparathyroidism]. Hyperparathyroidism is able to determine suddenly after a very poor clinical history a deep coma : in such a condition, the diagnosis with the paraneoplastic hypercalcemia may be a difficult one : cervicotomy can be the hero\u00efc way to lead to diagnosis and in the same time to perform treatment. To avoid such a dramatic situation, the authors propose cervicotomy for every patient suspected of P.T.H. adenoma, when calcemia is higher than 115 mg c/l, even if the symptoms are very slight or nil."} {"id": "PMID:183275", "title": "[Congenital type II dyserythropoiesis].", "content": "The authors report a case of congenital dyserythropoieses, type II, the diagnosis of which was made in a young 15 year old girl with anemia, sub-clinical jaundice and splenomegaly. The following three criteria were found: erythroblastic hyperplasia with a high percentage of binuclear cells, a double peripheral red cell membrane under the electron microscope and a positive Ham-Dacle test. An isotopic study showed a double process or erythropoiesis which was inefficacious and peripheral hemolysis. In connection with this case, the authors then recall the main characteristics of the three types of congenital dyserythropoiesis. The origin and consequences of the peripheral membrane excess of the erythroblasts characteristic of type II are then discussed.", "contents": "[Congenital type II dyserythropoiesis]. The authors report a case of congenital dyserythropoieses, type II, the diagnosis of which was made in a young 15 year old girl with anemia, sub-clinical jaundice and splenomegaly. The following three criteria were found: erythroblastic hyperplasia with a high percentage of binuclear cells, a double peripheral red cell membrane under the electron microscope and a positive Ham-Dacle test. An isotopic study showed a double process or erythropoiesis which was inefficacious and peripheral hemolysis. In connection with this case, the authors then recall the main characteristics of the three types of congenital dyserythropoiesis. The origin and consequences of the peripheral membrane excess of the erythroblasts characteristic of type II are then discussed."} {"id": "PMID:183281", "title": "[Patient compliance with drug prescriptions. General problem and the special case of rheumatology].", "content": "In all branches of medicine, a large percentage of patients do not take the drugs which are prescribed for them. This percentage is situated at about 40%. The authors study this phenomenon in connection with data in the literature drawn from studies with objective controls. Rheumatology does not escape from this problem, whether one considers inflammatory rheumatism or degenerative rheumatism. The authors provide data from a personal series observed in arthrosic patients with an anti-inflammatory drug under trial. The various implications of this phenomenon are briefly discussed.", "contents": "[Patient compliance with drug prescriptions. General problem and the special case of rheumatology]. In all branches of medicine, a large percentage of patients do not take the drugs which are prescribed for them. This percentage is situated at about 40%. The authors study this phenomenon in connection with data in the literature drawn from studies with objective controls. Rheumatology does not escape from this problem, whether one considers inflammatory rheumatism or degenerative rheumatism. The authors provide data from a personal series observed in arthrosic patients with an anti-inflammatory drug under trial. The various implications of this phenomenon are briefly discussed."} {"id": "PMID:183282", "title": "[Thoracic and abdominal actinomycoses. Anatomo-pathologic study of 5 cases].", "content": "The authors report 5 cases and study the thoracic and abdominal lesions of actinomycosis. This is a rare bacterial disease but not exceptional, discovered usually by chance on operative specimen on autopsy. The clinical and bacteriological diagnosis is very difficult although the lesions are characteristic. Thus it is always necessary to carry out biopsy and seek sulphur granules in the actinomycotic follicle. The differential diagnosis is usually easy with granulomycoses, but it is sometimes more difficult to distinguish the disease from nocardioses.", "contents": "[Thoracic and abdominal actinomycoses. Anatomo-pathologic study of 5 cases]. The authors report 5 cases and study the thoracic and abdominal lesions of actinomycosis. This is a rare bacterial disease but not exceptional, discovered usually by chance on operative specimen on autopsy. The clinical and bacteriological diagnosis is very difficult although the lesions are characteristic. Thus it is always necessary to carry out biopsy and seek sulphur granules in the actinomycotic follicle. The differential diagnosis is usually easy with granulomycoses, but it is sometimes more difficult to distinguish the disease from nocardioses."} {"id": "PMID:183283", "title": "[Hematologic manifestations of thymomas].", "content": "The hematologic manifestations during thymomas are dominated by erythroblastopenia. Though, the other series can be affected and red series can present other troubles. The authors report two cases, one with erythroblasto-penia-hypogammaglobulinemia, the other with polycythemia, and a review of the literature attempt to make the point on the subject.", "contents": "[Hematologic manifestations of thymomas]. The hematologic manifestations during thymomas are dominated by erythroblastopenia. Though, the other series can be affected and red series can present other troubles. The authors report two cases, one with erythroblasto-penia-hypogammaglobulinemia, the other with polycythemia, and a review of the literature attempt to make the point on the subject."} {"id": "PMID:183284", "title": "[Study of the action of sultopride on psychomotor agitation. Apropos of 31 cases].", "content": "A study of sultopride, a new derivative of the substituted anisamides, has shown that this neuroleptic drug reduces markedly and rapidly psychomotor agitation, especially its aggressive component. It also has an action on hallucinations. Its indications, in order of efficacy, are states of acute agitation, psychotic states during the active phase, acute manifestations of alcoholism and behaviour disorders such as expansivity, impulsivity and agressivity. Its tolerance is good considering its strong activity.", "contents": "[Study of the action of sultopride on psychomotor agitation. Apropos of 31 cases]. A study of sultopride, a new derivative of the substituted anisamides, has shown that this neuroleptic drug reduces markedly and rapidly psychomotor agitation, especially its aggressive component. It also has an action on hallucinations. Its indications, in order of efficacy, are states of acute agitation, psychotic states during the active phase, acute manifestations of alcoholism and behaviour disorders such as expansivity, impulsivity and agressivity. Its tolerance is good considering its strong activity."} {"id": "PMID:183285", "title": "[The plateau of the apex cardiogram].", "content": "The apex cardiogram should normally include a flat part, but when one looks carefully, one may note that this flat part normally includes a flat wave between the descending part from the first summit and the part rising towards the second summit. This is therefore something which occurs in the middle of systole. Now, quite different curves, such as those of ventricular volume collected by rheography or cineangiography, also show a mesodiastolic occurence. As far as clinical medicine is concerned, it is expressed more frequently during proto or telesystole, rather than during mesosystole, which may be totally free of abnormal waves. What thus occurs in mesosystole? This is the question which is raised by these findings]", "contents": "[The plateau of the apex cardiogram]. The apex cardiogram should normally include a flat part, but when one looks carefully, one may note that this flat part normally includes a flat wave between the descending part from the first summit and the part rising towards the second summit. This is therefore something which occurs in the middle of systole. Now, quite different curves, such as those of ventricular volume collected by rheography or cineangiography, also show a mesodiastolic occurence. As far as clinical medicine is concerned, it is expressed more frequently during proto or telesystole, rather than during mesosystole, which may be totally free of abnormal waves. What thus occurs in mesosystole? This is the question which is raised by these findings]"} {"id": "PMID:183286", "title": "[Contribution of cytochemistry and delayed hypersensitivity skin tests in the diagnosis and prognosis of chronic lymphoproliferative syndromes].", "content": "Cytochemistry is disappointing in lymphoproliferative syndromes for it does not permit one to classify the various diseases with certainty. In the early stages, if the three indices are lowered, the prognosis seems poorer. A study of glucuronidase permits, in hyperlymphocytosis, one to differentiate benign from malignant lymphocytes, but does not permit one to differentiate from one another, the other chronic lymphoproliferative syndromes. The acid phosphatase is interesting in the study of hairy cell leukemia. Finally, it was not possible to distinguish chronic lymphoid leukemia from leukemia with lymphosarcomatous cells, nor from the cytochemical point of view nor using tests for delayed hypersensitivity.", "contents": "[Contribution of cytochemistry and delayed hypersensitivity skin tests in the diagnosis and prognosis of chronic lymphoproliferative syndromes]. Cytochemistry is disappointing in lymphoproliferative syndromes for it does not permit one to classify the various diseases with certainty. In the early stages, if the three indices are lowered, the prognosis seems poorer. A study of glucuronidase permits, in hyperlymphocytosis, one to differentiate benign from malignant lymphocytes, but does not permit one to differentiate from one another, the other chronic lymphoproliferative syndromes. The acid phosphatase is interesting in the study of hairy cell leukemia. Finally, it was not possible to distinguish chronic lymphoid leukemia from leukemia with lymphosarcomatous cells, nor from the cytochemical point of view nor using tests for delayed hypersensitivity."} {"id": "PMID:183287", "title": "[Multiple lipomas of the colon and rectum].", "content": "The authors report a case of multiple circumscribed colonic lipomas and undertake a review of the literature. Since the end of the 18th century, 45 clinical and autopsy cases have been reported. These exceptional lesions are sometimes strictly latent and discovered by chance, sometimes they may give rise to a picture of chronic intestinal obstruction and, more rarely, that of intussusception. Comparison of radiology and colonoscopy permits one to better suspect the diagnosis for there are unusual signs concerning both lesions. The treatment is mainly surgical but sometimes lipomectomy by the endoscopic route may be carried out when the lesions are not numerous.", "contents": "[Multiple lipomas of the colon and rectum]. The authors report a case of multiple circumscribed colonic lipomas and undertake a review of the literature. Since the end of the 18th century, 45 clinical and autopsy cases have been reported. These exceptional lesions are sometimes strictly latent and discovered by chance, sometimes they may give rise to a picture of chronic intestinal obstruction and, more rarely, that of intussusception. Comparison of radiology and colonoscopy permits one to better suspect the diagnosis for there are unusual signs concerning both lesions. The treatment is mainly surgical but sometimes lipomectomy by the endoscopic route may be carried out when the lesions are not numerous."} {"id": "PMID:183292", "title": "Focal glomerular sclerosis.", "content": "Focal glomerular sclerosis was diagnosed in nine patients by renal biopsy. Proteinuria, hematuria, hypertension, and slowly progressive renal insufficiency unresponsive to corticosteroid and immunosuppressive therapy were consistent clinical findings. Focal, segmental, and global glomerular sclerosis with intraluminal deposits of hypereosinophilic and strongly PAS-positive material, intracapillary foam cells, and moderate interstitial involvement were consistent morphologic findings. The importance of this clinicopathologic entity in the spectrum of renal diseases has only recently been appreciated.", "contents": "Focal glomerular sclerosis. Focal glomerular sclerosis was diagnosed in nine patients by renal biopsy. Proteinuria, hematuria, hypertension, and slowly progressive renal insufficiency unresponsive to corticosteroid and immunosuppressive therapy were consistent clinical findings. Focal, segmental, and global glomerular sclerosis with intraluminal deposits of hypereosinophilic and strongly PAS-positive material, intracapillary foam cells, and moderate interstitial involvement were consistent morphologic findings. The importance of this clinicopathologic entity in the spectrum of renal diseases has only recently been appreciated."} {"id": "PMID:183294", "title": "Virus peneumonia following measles: a virological and histological study of autopsy material.", "content": "Adenovirus, measles virus and herpesvirus were found to be responsible for the serious non-bacterial bronchiolar and interstitial necrosis in post-measles pneumonia in underprivlieged non-White children less than 4 years of age in Cape Town. Secondary bacterial bronchopneumonia, possibly antibiotically suppressed, proved to be less important in accounting for the extensive lung damage in 18 fatal cases that were examined virologically and histologically.", "contents": "Virus peneumonia following measles: a virological and histological study of autopsy material. Adenovirus, measles virus and herpesvirus were found to be responsible for the serious non-bacterial bronchiolar and interstitial necrosis in post-measles pneumonia in underprivlieged non-White children less than 4 years of age in Cape Town. Secondary bacterial bronchopneumonia, possibly antibiotically suppressed, proved to be less important in accounting for the extensive lung damage in 18 fatal cases that were examined virologically and histologically."} {"id": "PMID:183295", "title": "[Synovial sarcoma in the region of the head and neck].", "content": "A young woman with primary cervical synovial sarcoma above the collar-bone is described. Synovial sarcomas of the head and neck are infrequently reported. The pathology, treatment and progress appear to be very similar to that of synovial sarcomas situated elsewhere. It appears that primary lesions occur in younger people and that the survival rate is better than that for synovial sarcoma elsewhere.", "contents": "[Synovial sarcoma in the region of the head and neck]. A young woman with primary cervical synovial sarcoma above the collar-bone is described. Synovial sarcomas of the head and neck are infrequently reported. The pathology, treatment and progress appear to be very similar to that of synovial sarcomas situated elsewhere. It appears that primary lesions occur in younger people and that the survival rate is better than that for synovial sarcoma elsewhere."} {"id": "PMID:183296", "title": "Involvement of the nipple and areola in carcinoma of the breast.", "content": "The records of all patients in whom a mastectomy was performed for carcinoma of the breast at this clinic during a recent two year period were reviewed, and the gross specimens were re-examined to study the incidence of cancerous involvement of the nipple and areola and related local clinical findings. Cancer was present in the nipple or areola, or both, in 12.2 per cent of the specimens. When the nipple and areola were clinically normal, involvement of the nipple and areola by carcinoma was rare if the primary tumor was less than 2 centimeters in diameter and was not situated behind the areola.", "contents": "Involvement of the nipple and areola in carcinoma of the breast. The records of all patients in whom a mastectomy was performed for carcinoma of the breast at this clinic during a recent two year period were reviewed, and the gross specimens were re-examined to study the incidence of cancerous involvement of the nipple and areola and related local clinical findings. Cancer was present in the nipple or areola, or both, in 12.2 per cent of the specimens. When the nipple and areola were clinically normal, involvement of the nipple and areola by carcinoma was rare if the primary tumor was less than 2 centimeters in diameter and was not situated behind the areola."} {"id": "PMID:183297", "title": "The use of radioactive cesium chloride for imaging of malignant and benign pulmonary lesions.", "content": "129CsCl was investigated as an agent for imaging tumors of the lung, and based on the results of 56 patients studied, it has proved to be highly sensitive in detecting primary malignant tumors of the lung. The differentiation between pulmonary malignant lesions and tuberculosis appears to be feasible. However, false-positive images in patients with benign conditions are inevitable.", "contents": "The use of radioactive cesium chloride for imaging of malignant and benign pulmonary lesions. 129CsCl was investigated as an agent for imaging tumors of the lung, and based on the results of 56 patients studied, it has proved to be highly sensitive in detecting primary malignant tumors of the lung. The differentiation between pulmonary malignant lesions and tuberculosis appears to be feasible. However, false-positive images in patients with benign conditions are inevitable."} {"id": "PMID:183298", "title": "Primary carcinoma of the liver.", "content": "Since 1947, 173 patients have been seen with primary carcinoma of the liver; 68 percent had hepatomas, 26 percent cholangiocarcinomas, and 6 percent mixed-cell carcinomas. Of these patients, 9 percent were Stage I or unstaged, whereas 28 percent were Stage III and had short lengths of survival. The 108 patients with Stage II carcinoma of the liver were analyzed according to treatment regimens. Thirty-one patients were observed but untreated; 47 patients were treated by systemic chemotherapy and 25 patients were treated by surgical resection. Three patients were treated by infusion chemotherapy and two by dearterialization. When primary carcinoma of the liver is resectable, approximately 20 percent of patients may be expected to become long-term survivors. If not resectable, short-term improvement in length of survival (8 to 13 months) may be obtained by systemic or infusion chemotherapy and by hepatic dearterialization. Earlier diagnosis and an aggressive surgical approach lends hope for some cures for patients with this difficult disease.", "contents": "Primary carcinoma of the liver. Since 1947, 173 patients have been seen with primary carcinoma of the liver; 68 percent had hepatomas, 26 percent cholangiocarcinomas, and 6 percent mixed-cell carcinomas. Of these patients, 9 percent were Stage I or unstaged, whereas 28 percent were Stage III and had short lengths of survival. The 108 patients with Stage II carcinoma of the liver were analyzed according to treatment regimens. Thirty-one patients were observed but untreated; 47 patients were treated by systemic chemotherapy and 25 patients were treated by surgical resection. Three patients were treated by infusion chemotherapy and two by dearterialization. When primary carcinoma of the liver is resectable, approximately 20 percent of patients may be expected to become long-term survivors. If not resectable, short-term improvement in length of survival (8 to 13 months) may be obtained by systemic or infusion chemotherapy and by hepatic dearterialization. Earlier diagnosis and an aggressive surgical approach lends hope for some cures for patients with this difficult disease."} {"id": "PMID:183299", "title": "The protective role of intraperitoneal antibiotic irrigation in contaminated penetrating wounds of the cecum.", "content": "Neomycin (500 mg.), polymyxin (500,000 U.), and bacitracin (50,000 U.) in one liter of saline, used as an abdominal irrigation solution, protects dogs against intraperitoneal infection and wound infections and markedly curtails adhesion formation after peritoneal contamination with cecal contents. Dogs treated with topical antibiotics after cecal puncture and local contamination were almost identical to control dogs without contamination. Equal volumes of saline irrigation offered no therapeutic advantage despite the theoretical benefit of diluting the bacterial and chemical challenge. Reported results are statistically significant (rho less than or equal to 0.05).", "contents": "The protective role of intraperitoneal antibiotic irrigation in contaminated penetrating wounds of the cecum. Neomycin (500 mg.), polymyxin (500,000 U.), and bacitracin (50,000 U.) in one liter of saline, used as an abdominal irrigation solution, protects dogs against intraperitoneal infection and wound infections and markedly curtails adhesion formation after peritoneal contamination with cecal contents. Dogs treated with topical antibiotics after cecal puncture and local contamination were almost identical to control dogs without contamination. Equal volumes of saline irrigation offered no therapeutic advantage despite the theoretical benefit of diluting the bacterial and chemical challenge. Reported results are statistically significant (rho less than or equal to 0.05)."} {"id": "PMID:183305", "title": "Comparison of two types of endothelial cells in long term culture.", "content": "Bovine aortic endothelial cells have been serially subcultured and maintained for ten months (24 passages) without any apparent loss of endothelial-like properties. There appear to be two endothelial cell types; one type is mononucleated, 40-60 mu in diameter, and the other (giant) cell type, multinucleate and 300-600 mu in diameter. Both cell types were identified as endothelial cells by established criteria; 1. ultrastructurally, by the presence of Weibel-Palade bodies, microfilaments and pinocytotic vesicles and 2. immunologically, by the presence of factor VIII antigen and thrombosthenin.", "contents": "Comparison of two types of endothelial cells in long term culture. Bovine aortic endothelial cells have been serially subcultured and maintained for ten months (24 passages) without any apparent loss of endothelial-like properties. There appear to be two endothelial cell types; one type is mononucleated, 40-60 mu in diameter, and the other (giant) cell type, multinucleate and 300-600 mu in diameter. Both cell types were identified as endothelial cells by established criteria; 1. ultrastructurally, by the presence of Weibel-Palade bodies, microfilaments and pinocytotic vesicles and 2. immunologically, by the presence of factor VIII antigen and thrombosthenin."} {"id": "PMID:183306", "title": "Studies of the thromboplastic effect of human plasma lipoproteins.", "content": "Human plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addtion of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma. Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.", "contents": "Studies of the thromboplastic effect of human plasma lipoproteins. Human plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addtion of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma. Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed."} {"id": "PMID:183308", "title": "Intracytoplasmic uncoated capsids of human cytomegalovirus.", "content": "It has been generally accepted that capsids found in the cytoplasm of infected fibroblasts by adapted strain human cytomegalovirus (CMV) have bristle-like surface coating on them. This coating was said to be one of the important differences of CMV from herpes simplex virus. As well known, capsids of CMV increased in their over-all diameter through the process of moving from the nucleus to the cytoplasm. In some instances, however, uncoated capsids were detected in the cytoplasmic portions especially in the vicinity of tubular structures in the cytoplasm. It seemed that these uncoated capsids might be formed in the cytoplasm but had not emigrated from the nucleus.", "contents": "Intracytoplasmic uncoated capsids of human cytomegalovirus. It has been generally accepted that capsids found in the cytoplasm of infected fibroblasts by adapted strain human cytomegalovirus (CMV) have bristle-like surface coating on them. This coating was said to be one of the important differences of CMV from herpes simplex virus. As well known, capsids of CMV increased in their over-all diameter through the process of moving from the nucleus to the cytoplasm. In some instances, however, uncoated capsids were detected in the cytoplasmic portions especially in the vicinity of tubular structures in the cytoplasm. It seemed that these uncoated capsids might be formed in the cytoplasm but had not emigrated from the nucleus."} {"id": "PMID:183309", "title": "Leukocyte adenosine triphosphatase activity in human bronchial asthma.", "content": "Changes in adenosine triphosphatase (ATPase) activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Estimation of the leukocyte Mg++- and Ca++- dependent ATPases was carried out according to Hadden's method, incubating ATP with the membrane fraction of the leukocyte. The leukocyte ATPase activity was significantly elevated among asthmatic patients compared with control subjects. This elevated ATPase was seen in all asthmatics irrespective of acute attacks or the drug treatment. There was no clear correlation between the activity of ATPase and the percentage of leukocytes, neutrophils and eosinophils. There was no relationship between ATPase activity and adenyl cyclase activity of the same leukocytes from asthmatic patients.", "contents": "Leukocyte adenosine triphosphatase activity in human bronchial asthma. Changes in adenosine triphosphatase (ATPase) activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Estimation of the leukocyte Mg++- and Ca++- dependent ATPases was carried out according to Hadden's method, incubating ATP with the membrane fraction of the leukocyte. The leukocyte ATPase activity was significantly elevated among asthmatic patients compared with control subjects. This elevated ATPase was seen in all asthmatics irrespective of acute attacks or the drug treatment. There was no clear correlation between the activity of ATPase and the percentage of leukocytes, neutrophils and eosinophils. There was no relationship between ATPase activity and adenyl cyclase activity of the same leukocytes from asthmatic patients."} {"id": "PMID:183310", "title": "Further study on the turnover calculation of lung lecithins.", "content": "Using the data reported previously by Moriya and Kanoh, the metabolic turnover of rat lung lecithins was calculated on the basis of the new assumption that the formation rate (Va) of lecithins from diacylglycerols did not equal the disappearance rate (Vb) of lecithins because of the presence of precursors other than diacylglycerols. The ratio of Va/Vb was almost the same in dienoic lecithin as that for total lecithins, whereas a very low ratio was found in saturated and hexaenoic species. The turnover time of lung lecithins estimated was markedly shorter than those determined in much later experimental periods after administration of labeled precursors. The reason for this discrepancy was discussed.", "contents": "Further study on the turnover calculation of lung lecithins. Using the data reported previously by Moriya and Kanoh, the metabolic turnover of rat lung lecithins was calculated on the basis of the new assumption that the formation rate (Va) of lecithins from diacylglycerols did not equal the disappearance rate (Vb) of lecithins because of the presence of precursors other than diacylglycerols. The ratio of Va/Vb was almost the same in dienoic lecithin as that for total lecithins, whereas a very low ratio was found in saturated and hexaenoic species. The turnover time of lung lecithins estimated was markedly shorter than those determined in much later experimental periods after administration of labeled precursors. The reason for this discrepancy was discussed."} {"id": "PMID:183311", "title": "Further study on the effects of LH-RH in rat anterior pituitary.", "content": "As to the mechanism of the action of LH-RH on rat anterior pituitary, the participation of the adenylate cyclase system in gonadotropin release has been clarified. The authors previously reported that LH-RH increased the RNA synthesis in the rat anterior pituitary. In this study, the significance of the increase of RNA synthesis by LH-RH and the relationship between the adenylate cyclase system and the RNA synthesis system were investigated and the following results were obtained. (1) LH-RH induces not only the release of LH but also its synthesis in the rat anterior pituitary, and furthermore, RNA synthesis participates in LH synthesis. (2) The effects of LH-RH on RNA synthesis appeared to be independent from the effects on the adenylate cyclase system.", "contents": "Further study on the effects of LH-RH in rat anterior pituitary. As to the mechanism of the action of LH-RH on rat anterior pituitary, the participation of the adenylate cyclase system in gonadotropin release has been clarified. The authors previously reported that LH-RH increased the RNA synthesis in the rat anterior pituitary. In this study, the significance of the increase of RNA synthesis by LH-RH and the relationship between the adenylate cyclase system and the RNA synthesis system were investigated and the following results were obtained. (1) LH-RH induces not only the release of LH but also its synthesis in the rat anterior pituitary, and furthermore, RNA synthesis participates in LH synthesis. (2) The effects of LH-RH on RNA synthesis appeared to be independent from the effects on the adenylate cyclase system."} {"id": "PMID:183314", "title": "The specificity of the 3beta-hydroxysteroid dehydrogenase activity of bovine ovaries toward dehydroepiandrosterone and pregnenolone: evidence for multiple enzymes.", "content": "The 3beta-hydroxysteroid dehydrogenase activity in whole bovine ovaries was systematically studied using dehydroepiandrosterone (3beta-hydroxy-5-androsten-17-one) and pregnenolone (3 beta-hydroxy-5-pregnen-20-one) as substrates, in order to determine whether, in this tissue, the same or different 3beta-hydroxysteroid dehydrogenases metabolize these steroids. The majority of the activity, with both substrates was found in the microsomes. Detergent extraction of the microsomes indicated that more than one enzyme was present in this fraction. A number of experiments on the Triton X-100 extract of the microsomes (the stability of the activity, its nucleotide specificity and kinetic analyses) were most simply explained by a single enzyme metabolizing both steroids. However, the stereospecificity of hydride-ion transfer from pregnenolone to NAD+ (B transfer) was different than that from dehydroepiandrosterone to NAD+ (A and B transfer). Thus, as no single enzyme is known to catalyze the transfer of hydride-ion to both sides of NAD+, it is proposed that there are at least two 3beta-hydroxysteroid dehydrogenases in the Triton X-100 extract.", "contents": "The specificity of the 3beta-hydroxysteroid dehydrogenase activity of bovine ovaries toward dehydroepiandrosterone and pregnenolone: evidence for multiple enzymes. The 3beta-hydroxysteroid dehydrogenase activity in whole bovine ovaries was systematically studied using dehydroepiandrosterone (3beta-hydroxy-5-androsten-17-one) and pregnenolone (3 beta-hydroxy-5-pregnen-20-one) as substrates, in order to determine whether, in this tissue, the same or different 3beta-hydroxysteroid dehydrogenases metabolize these steroids. The majority of the activity, with both substrates was found in the microsomes. Detergent extraction of the microsomes indicated that more than one enzyme was present in this fraction. A number of experiments on the Triton X-100 extract of the microsomes (the stability of the activity, its nucleotide specificity and kinetic analyses) were most simply explained by a single enzyme metabolizing both steroids. However, the stereospecificity of hydride-ion transfer from pregnenolone to NAD+ (B transfer) was different than that from dehydroepiandrosterone to NAD+ (A and B transfer). Thus, as no single enzyme is known to catalyze the transfer of hydride-ion to both sides of NAD+, it is proposed that there are at least two 3beta-hydroxysteroid dehydrogenases in the Triton X-100 extract."} {"id": "PMID:183315", "title": "Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H.", "content": "Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives.", "contents": "Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H. Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives."} {"id": "PMID:183316", "title": "Ribonucleases and neoplasia.", "content": "Biochemical data provide good evidence of a lack of acid and alkaline RNase activities in ascites tumour cells. Analyses of whole solid tumours appear of doubtful value, but fractionation studies reveal RNase deficiencies in mitochondrial fractions whereas inconsistent results are reported for microsomal fractions. Nuclei, nucleoli, and ribosomes isolated from tumours show relatively weak activities. Large variations are noted in determinations on purified lysosomes. Histochemical analyses by two different approaches demonstrate a multifocal loss of RNase activities in preneoplastic tissues, a lack of activities in cancer cells, and the presence of appreciable activities in stromal tissue and necrotic areas of tumours. These results suggest that RNase activities found in homogenates and cellular fractions of heterogeneous tumours may derive mainly from stromal cells, phagocytes, and extracellular fluids of necrotic areas. A close correlation seems to exist between activation of RNases and tumour regression. A large variety of therapeutic agents induce increases in tumour RNase activities whereas ineffective agents do not. The activation of RNases precedes obvious regression and apparently represents de novo synthesis of RNases in cancer cells. It emerges from these studies that loss of RNase activities could represent a critical event in carcinogenesis, that RNase deficiencies would persist in cancer cells, and that RNase activation would be closely associated with tumour regression. Losses of RNase activities in preneoplastic tissues are followed by changes in the properties of cytoplasmic RNA probably due to alterations in ribosomes in areas of neoplastic transformation. Deficiencies in the RNase system could be the source of abnormalities in cellular RNA or RNA-containing particles that would lead to neoplasia.", "contents": "Ribonucleases and neoplasia. Biochemical data provide good evidence of a lack of acid and alkaline RNase activities in ascites tumour cells. Analyses of whole solid tumours appear of doubtful value, but fractionation studies reveal RNase deficiencies in mitochondrial fractions whereas inconsistent results are reported for microsomal fractions. Nuclei, nucleoli, and ribosomes isolated from tumours show relatively weak activities. Large variations are noted in determinations on purified lysosomes. Histochemical analyses by two different approaches demonstrate a multifocal loss of RNase activities in preneoplastic tissues, a lack of activities in cancer cells, and the presence of appreciable activities in stromal tissue and necrotic areas of tumours. These results suggest that RNase activities found in homogenates and cellular fractions of heterogeneous tumours may derive mainly from stromal cells, phagocytes, and extracellular fluids of necrotic areas. A close correlation seems to exist between activation of RNases and tumour regression. A large variety of therapeutic agents induce increases in tumour RNase activities whereas ineffective agents do not. The activation of RNases precedes obvious regression and apparently represents de novo synthesis of RNases in cancer cells. It emerges from these studies that loss of RNase activities could represent a critical event in carcinogenesis, that RNase deficiencies would persist in cancer cells, and that RNase activation would be closely associated with tumour regression. Losses of RNase activities in preneoplastic tissues are followed by changes in the properties of cytoplasmic RNA probably due to alterations in ribosomes in areas of neoplastic transformation. Deficiencies in the RNase system could be the source of abnormalities in cellular RNA or RNA-containing particles that would lead to neoplasia."} {"id": "PMID:183321", "title": "Lipoprotein composition and lipoprotein interrelations in 50-year-old men with hyperlipoproteinaemia.", "content": "The serum lipoprotein (LP) composition and LP lipid interrelations were studied in 50-year-old men with different types of hyperlipoproteinaemia (HLP) and in randomly sampled health controls from the same population. The ratio cholesterol/triglycerides in very low density lipoproteins (VLDL)was high in HLP type III. The other types of HLP showed ratios not significantly different from the controls. The low density lipoprotein (LDL) cholesterol concentration was similar in controls, type III and type IV while, by definition, higher values were seen in type II A and II B. All types of HLP showed statistically significantly higher LDL triglycerides than the controls. HLP type II A and II B showed cholesterol/triglyceride ratios in LDL similar to the controls. The corresponding ratio in type IV was lower than in the control subjects but the lowest ratio was seen in type III with a mean value below the 5th percentile of healthy controls. The high density lipoprotein (HDL) cholesterol concentration was decreased in HLP type IV. Apparently elevated HDL triglyceride levels were seen in all types of HLP with the highest mean value in type III. The LP lipid interclass relationships were analysed in the random sample of health men and compared to corresponding relationships in the different types of HLP. Apart from HLP type III and HLP type IV with low LDL cholesterol levels all other types of LP interconversions. Intype IV a significant negative correlation between VLDL concentration and LDL cholesterol concentration and the cholesterol/triglyceride ratio in VLDL. There were no significant correlations between LDL cholesterol concentration and VLDL lipid variables in other types of HLP and normolipidaemia.", "contents": "Lipoprotein composition and lipoprotein interrelations in 50-year-old men with hyperlipoproteinaemia. The serum lipoprotein (LP) composition and LP lipid interrelations were studied in 50-year-old men with different types of hyperlipoproteinaemia (HLP) and in randomly sampled health controls from the same population. The ratio cholesterol/triglycerides in very low density lipoproteins (VLDL)was high in HLP type III. The other types of HLP showed ratios not significantly different from the controls. The low density lipoprotein (LDL) cholesterol concentration was similar in controls, type III and type IV while, by definition, higher values were seen in type II A and II B. All types of HLP showed statistically significantly higher LDL triglycerides than the controls. HLP type II A and II B showed cholesterol/triglyceride ratios in LDL similar to the controls. The corresponding ratio in type IV was lower than in the control subjects but the lowest ratio was seen in type III with a mean value below the 5th percentile of healthy controls. The high density lipoprotein (HDL) cholesterol concentration was decreased in HLP type IV. Apparently elevated HDL triglyceride levels were seen in all types of HLP with the highest mean value in type III. The LP lipid interclass relationships were analysed in the random sample of health men and compared to corresponding relationships in the different types of HLP. Apart from HLP type III and HLP type IV with low LDL cholesterol levels all other types of LP interconversions. Intype IV a significant negative correlation between VLDL concentration and LDL cholesterol concentration and the cholesterol/triglyceride ratio in VLDL. There were no significant correlations between LDL cholesterol concentration and VLDL lipid variables in other types of HLP and normolipidaemia."} {"id": "PMID:183322", "title": "Dietary and drug treatment of hyperlipidaemia. A feasibility study in asymptomatic middle-aged men.", "content": "83 middle-aged men with different types of hyperlipoproteinaemia were recruited from a health examination survey. They were treated with diet for 3 months and with diet and drugs in combination over a 2-year period (63 men used drugs). The serum lipid reductions after the dietary period were 14% and 27% for serum cholesterol and triglycerides, respectively. After 2 years the corresponding reductions were 21% and 42%, indicating an additional effect of diet and drugs. There was an average body weight reduction of 4.3% during the first 3 months which was maintained over the 2-year period. Special considerations in treating asymptomatic individuals are discussed.", "contents": "Dietary and drug treatment of hyperlipidaemia. A feasibility study in asymptomatic middle-aged men. 83 middle-aged men with different types of hyperlipoproteinaemia were recruited from a health examination survey. They were treated with diet for 3 months and with diet and drugs in combination over a 2-year period (63 men used drugs). The serum lipid reductions after the dietary period were 14% and 27% for serum cholesterol and triglycerides, respectively. After 2 years the corresponding reductions were 21% and 42%, indicating an additional effect of diet and drugs. There was an average body weight reduction of 4.3% during the first 3 months which was maintained over the 2-year period. Special considerations in treating asymptomatic individuals are discussed."} {"id": "PMID:183318", "title": "[Effect of thymosterin A on the immunological reaction of mice].", "content": "Proliferaiton of thymus-dependent lymphocytes and immunological reaction of the line CBA mice immunized with sheep erythrocytes was studied as affected by thymosterol A. The data obtained confirmed the authors' assumptions on a stimulation effect of thymosterol A on division of thymocytes. Introduction of the mentioned preparation against a background of the antigenic aciton of sheep erythrocytes causes an increase in the amount of cells synthesizing hemolysins more than by 60% as compared to the control. The preparation effect depends on the dose. The data are presented, which makes it possible to assume that the mentioned effects may be due to the action of thymosterol A on the content and activity of the intracellular cyclic AMP.", "contents": "[Effect of thymosterin A on the immunological reaction of mice]. Proliferaiton of thymus-dependent lymphocytes and immunological reaction of the line CBA mice immunized with sheep erythrocytes was studied as affected by thymosterol A. The data obtained confirmed the authors' assumptions on a stimulation effect of thymosterol A on division of thymocytes. Introduction of the mentioned preparation against a background of the antigenic aciton of sheep erythrocytes causes an increase in the amount of cells synthesizing hemolysins more than by 60% as compared to the control. The preparation effect depends on the dose. The data are presented, which makes it possible to assume that the mentioned effects may be due to the action of thymosterol A on the content and activity of the intracellular cyclic AMP."} {"id": "PMID:183319", "title": "[Change in lipid metabolism in sports wrestlers under conditions of physical load and body dehydration].", "content": "Control of forty six sportsmen-wrestlers determined that the loss in weight accounting for 3.5% leads to a certain reduction of nonesterified fatty acids (NEFA) in venous blood and to a significant increase in the content of esterified fatty acids (EFA), beta-lipoproteids, phospholipids and cholesterol. Analogous as to the trend (excluding NEFA) but a little less pronounced changes these values occur after physical load on sportsmen who did not undergo dehydration. Under conditions of dehydration a 40-minute work on veloergograph caused additional changes in the values under study. An hour after finishing the physical work the total level of lipids as well as of their fractions such as beta-lipoproteids, EFA and cholesterol remains considerably higher than that in the control. Thus, the loss in weight itself as to the character of the changes arising in the lipid metabolism is to some extent similar to physical load suffered by a sportsman organism and therefore may exert unfavourable effect on the working capacity.", "contents": "[Change in lipid metabolism in sports wrestlers under conditions of physical load and body dehydration]. Control of forty six sportsmen-wrestlers determined that the loss in weight accounting for 3.5% leads to a certain reduction of nonesterified fatty acids (NEFA) in venous blood and to a significant increase in the content of esterified fatty acids (EFA), beta-lipoproteids, phospholipids and cholesterol. Analogous as to the trend (excluding NEFA) but a little less pronounced changes these values occur after physical load on sportsmen who did not undergo dehydration. Under conditions of dehydration a 40-minute work on veloergograph caused additional changes in the values under study. An hour after finishing the physical work the total level of lipids as well as of their fractions such as beta-lipoproteids, EFA and cholesterol remains considerably higher than that in the control. Thus, the loss in weight itself as to the character of the changes arising in the lipid metabolism is to some extent similar to physical load suffered by a sportsman organism and therefore may exert unfavourable effect on the working capacity."} {"id": "PMID:183323", "title": "Antibiotic managment in renal failure.", "content": "This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.", "contents": "Antibiotic managment in renal failure. This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary."} {"id": "PMID:183324", "title": "Interaction of ultrasound with neoplastic tissue: IV. alteration of biologic activity in cells derived from rat Wilms' tumor sonicated in vivo.", "content": "Paired Wistar-Furth male rats were implanted subcutaneously with the Furth-Columbia rat Wilms' tumor. Seven days after implantation the tumors were either subjected to therapeutic ultrasound irradiation or were left as untreated controls. On the ninth day after implantation the animals were sacrificed, and suspensions of cells were made from the excised tumors by trypsinization. The cells were counted using trypan blue dye as an indicator of viability. New rats were then implanted with cells either from sonicated tumors or cells from controls. In half the recipient animals the suspensions were matched by total cell count. In the other half of the rats cell counts were matches for viability by the dye exclusion test. Tumors developed in a total of 8 of 11 rats receiving control cells and they died. A palpable tumor did not develop in any rat receiving cells fromsonicated tumors during the ninety-day study period. Surviving rats were challenged with Wilms' tumor by trocar implant. Tumor developed in all recipients, and they died.", "contents": "Interaction of ultrasound with neoplastic tissue: IV. alteration of biologic activity in cells derived from rat Wilms' tumor sonicated in vivo. Paired Wistar-Furth male rats were implanted subcutaneously with the Furth-Columbia rat Wilms' tumor. Seven days after implantation the tumors were either subjected to therapeutic ultrasound irradiation or were left as untreated controls. On the ninth day after implantation the animals were sacrificed, and suspensions of cells were made from the excised tumors by trypsinization. The cells were counted using trypan blue dye as an indicator of viability. New rats were then implanted with cells either from sonicated tumors or cells from controls. In half the recipient animals the suspensions were matched by total cell count. In the other half of the rats cell counts were matches for viability by the dye exclusion test. Tumors developed in a total of 8 of 11 rats receiving control cells and they died. A palpable tumor did not develop in any rat receiving cells fromsonicated tumors during the ninety-day study period. Surviving rats were challenged with Wilms' tumor by trocar implant. Tumor developed in all recipients, and they died."} {"id": "PMID:183325", "title": "Radiolucent defects within renal pelvis.", "content": "Radiolucent filling defects within the renal pelvis are common findings in diagnositc urography, and because of their myriad causes the diagnostician is often faced with a challenging problem. Several of the more unusual causes of renal pelvis filling defects are described and their diagnosis, pathophysiology, and therapy discussed.", "contents": "Radiolucent defects within renal pelvis. Radiolucent filling defects within the renal pelvis are common findings in diagnositc urography, and because of their myriad causes the diagnostician is often faced with a challenging problem. Several of the more unusual causes of renal pelvis filling defects are described and their diagnosis, pathophysiology, and therapy discussed."} {"id": "PMID:183320", "title": "[Plasma prekallikrein activation by highly dispersed organic silica].", "content": "Human and animal blood plasm precallikrein was studied as activated by the high-dispersed preparations of silica (aerosils) which carry on their surface various chemically grafted organic radicals. It is shown that hydrophilic silica containing -COOH, -HN2, -OH groups, contrary to the hydrophobic ones, are efficient in activating human plasm precallikrein. Precallikrein activation is dependent on concentration of hydrophilic aerosil, temperature and specific surface of the activator.", "contents": "[Plasma prekallikrein activation by highly dispersed organic silica]. Human and animal blood plasm precallikrein was studied as activated by the high-dispersed preparations of silica (aerosils) which carry on their surface various chemically grafted organic radicals. It is shown that hydrophilic silica containing -COOH, -HN2, -OH groups, contrary to the hydrophobic ones, are efficient in activating human plasm precallikrein. Precallikrein activation is dependent on concentration of hydrophilic aerosil, temperature and specific surface of the activator."} {"id": "PMID:183334", "title": "[Study of certain components of the kinin system in acute purulent peritonitis].", "content": "Under study was the kinetics of changes in the kinin content, the activity of kininase and blood proteolytic activity in acute purulent peritonitis in 63 patients. The kinin activity was judged indirectly by the kinin level in blood. The results of the study indicated that in acute purulent peritonitis the kinin concentration in blood is decreased in proportion with the gravity of the disease course.", "contents": "[Study of certain components of the kinin system in acute purulent peritonitis]. Under study was the kinetics of changes in the kinin content, the activity of kininase and blood proteolytic activity in acute purulent peritonitis in 63 patients. The kinin activity was judged indirectly by the kinin level in blood. The results of the study indicated that in acute purulent peritonitis the kinin concentration in blood is decreased in proportion with the gravity of the disease course."} {"id": "PMID:183342", "title": "[Immunogenic properties of a polyvalent inactivated vaccine from respiratory viruses (IBR, Pi-3, Ad-1, Ad-3].", "content": "Studied was the authors' inactivated polyvalent vaccine having an adjuvant, prepared from the respiratory viruses IBR, Pi-3, Ad-1 and Ad-3. It was found that at the subcutaneous vaccination of calves and pregnant cows there were virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies as established by the 14th day following treatment. Revaccination was carried out on the twenty-eighth day when the antibodies reached high titers. The latter showed peak values on the 14th day following revaccination. The prevaccinal and vaccinal antibodies did not interfere with the process of immunogenesis. The virus-neutralizing antibodies against IBR had a titer of 5 log on the 150th day, while the virus-neutralizing and hemagglutination-inhibition antibodies against Pi-3 showed the same titer even after the 180th day following vaccination. There were in the milk of the vaccinated cows, in the seventh month of pregnancy, specific lactoglobulins of the IgA and IgG classes which were contained in the 27-36, 45-48 and 51-54 fractions, distributed in three peaks by their protein content. The level of the virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies against the inactivated vaccinal respiratory viruses showed that the subcutaneous treatment with the polyvalent vaccine leads to the production of antibodies that are secreted with milk", "contents": "[Immunogenic properties of a polyvalent inactivated vaccine from respiratory viruses (IBR, Pi-3, Ad-1, Ad-3]. Studied was the authors' inactivated polyvalent vaccine having an adjuvant, prepared from the respiratory viruses IBR, Pi-3, Ad-1 and Ad-3. It was found that at the subcutaneous vaccination of calves and pregnant cows there were virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies as established by the 14th day following treatment. Revaccination was carried out on the twenty-eighth day when the antibodies reached high titers. The latter showed peak values on the 14th day following revaccination. The prevaccinal and vaccinal antibodies did not interfere with the process of immunogenesis. The virus-neutralizing antibodies against IBR had a titer of 5 log on the 150th day, while the virus-neutralizing and hemagglutination-inhibition antibodies against Pi-3 showed the same titer even after the 180th day following vaccination. There were in the milk of the vaccinated cows, in the seventh month of pregnancy, specific lactoglobulins of the IgA and IgG classes which were contained in the 27-36, 45-48 and 51-54 fractions, distributed in three peaks by their protein content. The level of the virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies against the inactivated vaccinal respiratory viruses showed that the subcutaneous treatment with the polyvalent vaccine leads to the production of antibodies that are secreted with milk"} {"id": "PMID:183343", "title": "[Use of polyethylene glycol (PEG) in the isolation of the IBR virus].", "content": "Experiments were carried out to use polyethylene-glycol (PEG)--6000 in the isolation of the IBR virus from field material. The sedimentation with PEG proved easy, fast and selective. Large amounts of field material suspension could be treated which made it possible to attain volume concentration of such suspensions and to raise the relative concentration of the virus in them. Thus the virus could be isolated more quickly and in a more dependable way, avoiding the toxic effect of some of the initial materials on the cell culture.", "contents": "[Use of polyethylene glycol (PEG) in the isolation of the IBR virus]. Experiments were carried out to use polyethylene-glycol (PEG)--6000 in the isolation of the IBR virus from field material. The sedimentation with PEG proved easy, fast and selective. Large amounts of field material suspension could be treated which made it possible to attain volume concentration of such suspensions and to raise the relative concentration of the virus in them. Thus the virus could be isolated more quickly and in a more dependable way, avoiding the toxic effect of some of the initial materials on the cell culture."} {"id": "PMID:183344", "title": "[Study of Aujeszky's disease virus replication by using an immunofluorescent method].", "content": "Studied was the interrelationship between the Aujeszky's disease virus (the avirulent mutant strain MK and the virulent strain 2) and chick embryo cells during cultivation with and without 5-iod-2-desoxiuridine. In experiments with the virulent strain the presence of a granular antigen could be observed at the 4th hour following the infection of the nucleus. After the 10th hour the antigen showed migration from the nucleus toward the cytoplasm. After the 24th hour a complete destruction of the cellular monolayer was observed, along with the production of polynuclear cells. In the experiments with strain MK the antigen seemed to appear first in the cytoplasm after the 10th hour of infecting the cells, and after the 12th hour it was found in the nucleoplasm too. In this case full destruction of the cells set in after the 48th hour of infection. In the cultivation of strain MK in cell cultures containing 5-iod-2-desoxiuridine no disturbances in the normal cycle of reproduction was observed. The virus replicated equally well both with and without the antimetabolite. In the cultivation of the virulent strain 2 in cell cultures that contained 5-iod-2-desoxiuridine a coarse, granular antigen was noticed in the cytoplasm of single cells after the eighth hour of infection. After the 12th hour the nuclei of these cells manifested slight flourescence (hardly visible single granules). After the 48th hour the nuclei of the involved cells were swollen, and the cytoplasm presented slight, diffuse fluorescence, some of the cells being destroyed.", "contents": "[Study of Aujeszky's disease virus replication by using an immunofluorescent method]. Studied was the interrelationship between the Aujeszky's disease virus (the avirulent mutant strain MK and the virulent strain 2) and chick embryo cells during cultivation with and without 5-iod-2-desoxiuridine. In experiments with the virulent strain the presence of a granular antigen could be observed at the 4th hour following the infection of the nucleus. After the 10th hour the antigen showed migration from the nucleus toward the cytoplasm. After the 24th hour a complete destruction of the cellular monolayer was observed, along with the production of polynuclear cells. In the experiments with strain MK the antigen seemed to appear first in the cytoplasm after the 10th hour of infecting the cells, and after the 12th hour it was found in the nucleoplasm too. In this case full destruction of the cells set in after the 48th hour of infection. In the cultivation of strain MK in cell cultures containing 5-iod-2-desoxiuridine no disturbances in the normal cycle of reproduction was observed. The virus replicated equally well both with and without the antimetabolite. In the cultivation of the virulent strain 2 in cell cultures that contained 5-iod-2-desoxiuridine a coarse, granular antigen was noticed in the cytoplasm of single cells after the eighth hour of infection. After the 12th hour the nuclei of these cells manifested slight flourescence (hardly visible single granules). After the 48th hour the nuclei of the involved cells were swollen, and the cytoplasm presented slight, diffuse fluorescence, some of the cells being destroyed."} {"id": "PMID:183345", "title": "[Effects of concanavalin A on the adsorption and penetration of paramyxoviruses into cells].", "content": "The lectin concavaline A, when added to cell cultures of chick embryos and calf kidney one hour prior to their injection with the virus of the Newcastle disease and that of parainfluenza-3 in cattle produces no adverse effect on the cell receptors of these viruses. On cells treated with concavaline 60 per cent and more virions are adsorbed as compared with the untreated cells. This is explained by the fact that concavaline binds to the cellular and viral glucoproteins. Virions bound to concavaline do not penetrate into the cells. The titers of the paramyxoviruses obtained from lectin-treated cells were by 2 log. lower than the virus titers obtained from untreated cells. Mono- and bivalent concavalines inhibit more slightly the reproduction of para myxoviruses.", "contents": "[Effects of concanavalin A on the adsorption and penetration of paramyxoviruses into cells]. The lectin concavaline A, when added to cell cultures of chick embryos and calf kidney one hour prior to their injection with the virus of the Newcastle disease and that of parainfluenza-3 in cattle produces no adverse effect on the cell receptors of these viruses. On cells treated with concavaline 60 per cent and more virions are adsorbed as compared with the untreated cells. This is explained by the fact that concavaline binds to the cellular and viral glucoproteins. Virions bound to concavaline do not penetrate into the cells. The titers of the paramyxoviruses obtained from lectin-treated cells were by 2 log. lower than the virus titers obtained from untreated cells. Mono- and bivalent concavalines inhibit more slightly the reproduction of para myxoviruses."} {"id": "PMID:183348", "title": "[Glomus cell clusters of the lymph node].", "content": "Nine lymph nodes with so-called benign nevus cell nevi were studied by light microscopy. In three cases the lymph nodes were also examined by electron microscopy. The solitary or multiple cell clusters were 35-645 mu in diameter and were usually found in the lymph node capsule or cortex. They were more frequent in the older patients. There was no predisposition for either sex. Specific morphologic features allowing clear cytologic identification of the cells were not evidient. In particular, there was no indication that they represented nevus cells. However, they showed a great morphologic similarity to glomus cells. In addition, they were usually found near blood vessels. We assume that the cell clusters were hamartias related to glomangiomas. We call them glomus cell clusters.", "contents": "[Glomus cell clusters of the lymph node]. Nine lymph nodes with so-called benign nevus cell nevi were studied by light microscopy. In three cases the lymph nodes were also examined by electron microscopy. The solitary or multiple cell clusters were 35-645 mu in diameter and were usually found in the lymph node capsule or cortex. They were more frequent in the older patients. There was no predisposition for either sex. Specific morphologic features allowing clear cytologic identification of the cells were not evidient. In particular, there was no indication that they represented nevus cells. However, they showed a great morphologic similarity to glomus cells. In addition, they were usually found near blood vessels. We assume that the cell clusters were hamartias related to glomangiomas. We call them glomus cell clusters."} {"id": "PMID:183349", "title": "Characterization of two different factors chemotactic for cancer cells from tumor tissue.", "content": "Two different factors chemotactic for cancer cells were extracted in pseudoglobulin fraction of rat ascites hepatoma transplanted tissue. After chromatography on Sephadex G-50 and CM-sephadex, these factors were separated by gel filtration on Sephadex G-100. The factor a was further fractionated by immunoadsorbent chromatography with goat antirat gamma-globulin antibody and then with rabbit antirat hemoglobin antibody; it was a protein with a molecular weight of about 78,000, resembling a chemotactic factor previously reported, and its activity was thermolabile. The previously undescribed factor b was also a protein with a molecular weight of about 14,000 and its activity was thermostable. Intradermal injection of these factors at low concentrations induced an extravascular migration of circulating tumor cells and formation of metastatic secondary tumors; and little difference in the in vivo effect between these factors was observed. It was thus assumed that the combined action of these two factors may be involved in malignant invasion.", "contents": "Characterization of two different factors chemotactic for cancer cells from tumor tissue. Two different factors chemotactic for cancer cells were extracted in pseudoglobulin fraction of rat ascites hepatoma transplanted tissue. After chromatography on Sephadex G-50 and CM-sephadex, these factors were separated by gel filtration on Sephadex G-100. The factor a was further fractionated by immunoadsorbent chromatography with goat antirat gamma-globulin antibody and then with rabbit antirat hemoglobin antibody; it was a protein with a molecular weight of about 78,000, resembling a chemotactic factor previously reported, and its activity was thermolabile. The previously undescribed factor b was also a protein with a molecular weight of about 14,000 and its activity was thermostable. Intradermal injection of these factors at low concentrations induced an extravascular migration of circulating tumor cells and formation of metastatic secondary tumors; and little difference in the in vivo effect between these factors was observed. It was thus assumed that the combined action of these two factors may be involved in malignant invasion."} {"id": "PMID:183372", "title": "A study of the Ag factors in a British (West Midland) population.", "content": "168 sera from a British (West Midlands) population of normal blood donors were typed for the factors Ag (x, y, a1, d, t, c, g and h). The results were compared with the published data from other populations. The 8 factors were found in 27 different phenotypic combinations including a single instance of the combination Ag (y-h+) not previously reported. The occurrence of this phenotype is discussed in relation to the theoretical models of the genetic control of the Ag system.", "contents": "A study of the Ag factors in a British (West Midland) population. 168 sera from a British (West Midlands) population of normal blood donors were typed for the factors Ag (x, y, a1, d, t, c, g and h). The results were compared with the published data from other populations. The 8 factors were found in 27 different phenotypic combinations including a single instance of the combination Ag (y-h+) not previously reported. The occurrence of this phenotype is discussed in relation to the theoretical models of the genetic control of the Ag system."} {"id": "PMID:183373", "title": "[Biochemistry of benign-symmetrical lipomatosis (adenolipomatosis Launois-Bensaude, Madelung's disease)].", "content": "1. Total lipids, total cholesterol, cholesterol esters, phospholipids, triglycerides and free fatty acids as well as the fatty acids profiles of the different lipid classes were determined in serum, lipomatous and normal adipose tissue. Triglycerides were elevated in patient L's serum. The distribution of serum lipoproteins in this patient's serum showed a type IV according to Fredrickson. All other lipid parameters were within the normal range. Palmitoleic acid was increased nearly in all lipid fractions of the patients' sera as well as in the lipids of lipomatous subcutaneous adipose tissue. 2. The lipomatous adipose tissues of the patients showing no histological abnormalities revealed higher levels of cyclic AMP than normal subcutaneous adipose tissue. 3. Serum uric acid was normal (patient E.), between the normal and pathological range (patient L.) and elevated (patient W.). Urinary uric acid excretion was increased in all three patients. 4. 14C-glycine was overincorporated into urinary uric acid in all three patients. 5. Adenine phosphoribosyltransferase activities in the hemolysates were within the normal range. A decrease of hypoxanthine-guanine phosphoribosyltransferase activities could be demonstrated in two patients' (e., w.) erythrocytes. Erythrocyte phosphoribosylpyrophate synthetase activity was slightly increased in patient L.'s and twice the normal value in patient W.'s erythrocytes.", "contents": "[Biochemistry of benign-symmetrical lipomatosis (adenolipomatosis Launois-Bensaude, Madelung's disease)]. 1. Total lipids, total cholesterol, cholesterol esters, phospholipids, triglycerides and free fatty acids as well as the fatty acids profiles of the different lipid classes were determined in serum, lipomatous and normal adipose tissue. Triglycerides were elevated in patient L's serum. The distribution of serum lipoproteins in this patient's serum showed a type IV according to Fredrickson. All other lipid parameters were within the normal range. Palmitoleic acid was increased nearly in all lipid fractions of the patients' sera as well as in the lipids of lipomatous subcutaneous adipose tissue. 2. The lipomatous adipose tissues of the patients showing no histological abnormalities revealed higher levels of cyclic AMP than normal subcutaneous adipose tissue. 3. Serum uric acid was normal (patient E.), between the normal and pathological range (patient L.) and elevated (patient W.). Urinary uric acid excretion was increased in all three patients. 4. 14C-glycine was overincorporated into urinary uric acid in all three patients. 5. Adenine phosphoribosyltransferase activities in the hemolysates were within the normal range. A decrease of hypoxanthine-guanine phosphoribosyltransferase activities could be demonstrated in two patients' (e., w.) erythrocytes. Erythrocyte phosphoribosylpyrophate synthetase activity was slightly increased in patient L.'s and twice the normal value in patient W.'s erythrocytes."} {"id": "PMID:183374", "title": "[Further experimental investigations on the therapy of gas gangrene with ozone and oxygen (author's transl)].", "content": "In continuation of a recently-published investigation on the effect of intramuscular injections of an ozone-oxygen mixture on experimental gas gangrene in the guinea pig, 2 additional experiments were performed in order to establish the efficacy of the therapy when given twice daily instead of only once. Futhermore, the effect of an analogous therapy was investigated with the use of pure oxygen. The ozone-oxygen therapy reduced the death rate from 100% in untreated control animals to 73.6 and 70.0%, respectively, in the 2 series of experiments. The median survival times were prolonged from 0.56 and 1.33 days to 5.50 and 6.66 days. The use of oxygen twice daily reduced the death rates significantly even further to 57.0 and 47.9%. With this therapy the median survival time was increased to 8 and more than 12 days. The differences in therapeutic effect of the 2 gases were not, however, statistically significant. On account of its simple applicability previous experiments on animals it is proposed that this therapy be employed also in cases of human gas gangrene. In addition, the bactericidal effect of CaCl2, as used in this experimental study, on vegetative forms of Clostridia is demonstrated.", "contents": "[Further experimental investigations on the therapy of gas gangrene with ozone and oxygen (author's transl)]. In continuation of a recently-published investigation on the effect of intramuscular injections of an ozone-oxygen mixture on experimental gas gangrene in the guinea pig, 2 additional experiments were performed in order to establish the efficacy of the therapy when given twice daily instead of only once. Futhermore, the effect of an analogous therapy was investigated with the use of pure oxygen. The ozone-oxygen therapy reduced the death rate from 100% in untreated control animals to 73.6 and 70.0%, respectively, in the 2 series of experiments. The median survival times were prolonged from 0.56 and 1.33 days to 5.50 and 6.66 days. The use of oxygen twice daily reduced the death rates significantly even further to 57.0 and 47.9%. With this therapy the median survival time was increased to 8 and more than 12 days. The differences in therapeutic effect of the 2 gases were not, however, statistically significant. On account of its simple applicability previous experiments on animals it is proposed that this therapy be employed also in cases of human gas gangrene. In addition, the bactericidal effect of CaCl2, as used in this experimental study, on vegetative forms of Clostridia is demonstrated."} {"id": "PMID:183380", "title": "Cytomegalovirus replication and the host immune response.", "content": "Cytomegalovirus (CMV) is closely associated with host cellular structures, and this has a significant impact upon the immunologic response following infection. CMV may be recovered from a variety of body secretions and fluids during acute infection, and protracted shedding may supervene in some instances. The reasons for a variable host response to CMV infection remain unclear, and the mechanisms responsible for the establishment of persistence have not been worked out. CMV persistence and latency are discussed, and some recently derived relevant data are presented. An animal model has been developed consistent with clinical observations pertaining to CMV transmission with blood. Results obtained in the course of these and other studies support the concept of immunological activation of latent CMV. The timing of CMV infection relative to an unrelated antigenic challenge is probably critical in determining the emergence of immunodepression or enhancement. Some aspects of CMV sero-diagnosis are also reviewed.", "contents": "Cytomegalovirus replication and the host immune response. Cytomegalovirus (CMV) is closely associated with host cellular structures, and this has a significant impact upon the immunologic response following infection. CMV may be recovered from a variety of body secretions and fluids during acute infection, and protracted shedding may supervene in some instances. The reasons for a variable host response to CMV infection remain unclear, and the mechanisms responsible for the establishment of persistence have not been worked out. CMV persistence and latency are discussed, and some recently derived relevant data are presented. An animal model has been developed consistent with clinical observations pertaining to CMV transmission with blood. Results obtained in the course of these and other studies support the concept of immunological activation of latent CMV. The timing of CMV infection relative to an unrelated antigenic challenge is probably critical in determining the emergence of immunodepression or enhancement. Some aspects of CMV sero-diagnosis are also reviewed."} {"id": "PMID:183389", "title": "Cytomegalovirus infection in children undergoing open-heart surgery.", "content": "A group of 124 children undergoing open-heart surgery was followed prospectively in order to estimate the risk of cytomegalovirus (CMV) infection due to transfused blood.Ninety-three patients (75%) had complement fixation (CF) titers of < 1:4 against CMV on admission. Of this seronegative subgroup, nine patients (9.7%) subsequently became infected with CMV. All nine showed seroconversion, and six were viruric 12-14 weeks after surgery. Comparative seroepidemiological studies of the hospital population showed that in the age ranges studied (3-16 yr), the infections seen in the study group represented a significant excess over expectation. This infection rate was consistent with a model of transmission by blood transfusion with a risk of 2.7% per unit but not proven.Thirty-one patients had CF antibody to CMV on admission. CMV was isolated from 14% of urines of seropositive children both before and after surgery, but only two patients showed CF antibody rises to CMV. Thus the frequency of CMV infection associated with open-heart surgery and transfusion could not be calculated in the seropositive subgroup.CMV infection was not related to the primary diagnosis or to Down's syndrome.", "contents": "Cytomegalovirus infection in children undergoing open-heart surgery. A group of 124 children undergoing open-heart surgery was followed prospectively in order to estimate the risk of cytomegalovirus (CMV) infection due to transfused blood.Ninety-three patients (75%) had complement fixation (CF) titers of < 1:4 against CMV on admission. Of this seronegative subgroup, nine patients (9.7%) subsequently became infected with CMV. All nine showed seroconversion, and six were viruric 12-14 weeks after surgery. Comparative seroepidemiological studies of the hospital population showed that in the age ranges studied (3-16 yr), the infections seen in the study group represented a significant excess over expectation. This infection rate was consistent with a model of transmission by blood transfusion with a risk of 2.7% per unit but not proven.Thirty-one patients had CF antibody to CMV on admission. CMV was isolated from 14% of urines of seropositive children both before and after surgery, but only two patients showed CF antibody rises to CMV. Thus the frequency of CMV infection associated with open-heart surgery and transfusion could not be calculated in the seropositive subgroup.CMV infection was not related to the primary diagnosis or to Down's syndrome."} {"id": "PMID:183390", "title": "Hepatitis A.", "content": "Hepatitis A is a disease of worldwide distribution which occurs in endemic and epidemic form and is transmitted primarily by person-to-person contact through the fecal-oral route. Common source epidemics due to contamination of food are relatively common, and water-borne epidemics have been described less frequently. The presumed etiologic agent of hepatitis A has now been visualized by immune electron microscopic (IEM) techniques in early acute-illness-phase stools of humans with hepatitis A as well as in chimpanzees experimentally infected with material known to contain hepatitis A virus. In addition, several new serologic tests for the detection of antibody against hepatitis A virus have been described. These include complement fixation and immune adherence techniques. Current data suggest that hepatitis A is caused by a single viral agent lacking the morphologic heterogeneity of hepatitis B viral components and that there may be relative antigenic homogeneity between strains of virus recovered from various parts of the world. Serologic studies to date also indicate that hepatitis A virus is not a major contributing cause in post-transfusion hepatitis.", "contents": "Hepatitis A. Hepatitis A is a disease of worldwide distribution which occurs in endemic and epidemic form and is transmitted primarily by person-to-person contact through the fecal-oral route. Common source epidemics due to contamination of food are relatively common, and water-borne epidemics have been described less frequently. The presumed etiologic agent of hepatitis A has now been visualized by immune electron microscopic (IEM) techniques in early acute-illness-phase stools of humans with hepatitis A as well as in chimpanzees experimentally infected with material known to contain hepatitis A virus. In addition, several new serologic tests for the detection of antibody against hepatitis A virus have been described. These include complement fixation and immune adherence techniques. Current data suggest that hepatitis A is caused by a single viral agent lacking the morphologic heterogeneity of hepatitis B viral components and that there may be relative antigenic homogeneity between strains of virus recovered from various parts of the world. Serologic studies to date also indicate that hepatitis A virus is not a major contributing cause in post-transfusion hepatitis."} {"id": "PMID:183391", "title": "[Surface tension in rat lungs after quartz dust inhalation (author's transl)].", "content": "The influence of quartz dust (1000mg/m3) on surface tension in rat lungs was investigated. The exposure-times were 5, 15 and 30 hours. The animals were killed, 1, 7, 14, 28 and 90 days after quartz dust exposure and the surface tension was measured in a Wilhelmy balance. There was no significant difference between control animals and quartz dust animals in gammamax, gammamin and S. But there were significant differences in the same groups in hysteresis shape index and compressibility-coefficient.", "contents": "[Surface tension in rat lungs after quartz dust inhalation (author's transl)]. The influence of quartz dust (1000mg/m3) on surface tension in rat lungs was investigated. The exposure-times were 5, 15 and 30 hours. The animals were killed, 1, 7, 14, 28 and 90 days after quartz dust exposure and the surface tension was measured in a Wilhelmy balance. There was no significant difference between control animals and quartz dust animals in gammamax, gammamin and S. But there were significant differences in the same groups in hysteresis shape index and compressibility-coefficient."} {"id": "PMID:183392", "title": "Reduction of folate levels in the rat: Difference in depletion between the central and the peripheral nervous system.", "content": "1. Rats were deprived of dietary folate for 12 and 9.5 months in two experiments; one with and one without succinylsulfathiazole added to the diet. Folate levels decreased faster in the former experiment and the final blood values were lower. Tissue folate was examined in the latter experiment only. 2. The animals were repeatedly examined with neurological tests and compared with a control group supplemented with folic acid. Every test proved normal. Measurement of motor nerve conduction velocities after 12 months in the experiment where succinylsulfathiazole was given revealed lower velocities in the non-supplemented group. There was no difference between the groups in the experiment without succinylsulfathiazole. 3. In the latter experiment brain folate was reduced by only 16% in the non-supplemented animals compared with the controls, whereas whole blood folate fell by 60%, liver folate by 50% and sciatic nerve folate by 59%. 4. The central nervous system is resistant to systemic folate depletion, whereas the peripheral nerves are depleted to the same degree as the extra-neural tissues.", "contents": "Reduction of folate levels in the rat: Difference in depletion between the central and the peripheral nervous system. 1. Rats were deprived of dietary folate for 12 and 9.5 months in two experiments; one with and one without succinylsulfathiazole added to the diet. Folate levels decreased faster in the former experiment and the final blood values were lower. Tissue folate was examined in the latter experiment only. 2. The animals were repeatedly examined with neurological tests and compared with a control group supplemented with folic acid. Every test proved normal. Measurement of motor nerve conduction velocities after 12 months in the experiment where succinylsulfathiazole was given revealed lower velocities in the non-supplemented group. There was no difference between the groups in the experiment without succinylsulfathiazole. 3. In the latter experiment brain folate was reduced by only 16% in the non-supplemented animals compared with the controls, whereas whole blood folate fell by 60%, liver folate by 50% and sciatic nerve folate by 59%. 4. The central nervous system is resistant to systemic folate depletion, whereas the peripheral nerves are depleted to the same degree as the extra-neural tissues."} {"id": "PMID:183393", "title": "[Drug therapy of hyperthyroidism].", "content": "The possibilities of the treatment of hyperthyroidism are mentioned, in which cases the author especially deals with the medicamentous therapy, taking into consideration the different chemical groups (imidazol derivations, thiourazil derivations, perchlorates) and their therapeutic mechanisms. The indications and contraindications of this treatment and the possible side effects are compiled in form of a table. The in-vitro-parameters which are necessary for the observation of the course are estimated in their significance. The author deals with the problems of the additional treatment. Taking into consideration indications and contraindications as well as controls of the course of functional parameters the medicamentous therapy concerned is a treatment with a good prognosis. It is promising particularly in such cases, when suitable parameters are used for the solution of the question concerning the end of the therapy. For this purpose nowadays two tests are at our disposal: 1. modified Alexander's test (radioiodine-test and suppression test under thyreostatic therapy) and 2. TRH-test with radioimmunological determination of TSH. The treatment should be carried out in adequate endocrinological dispensaries, as there are certain risks in not optimal therapy.", "contents": "[Drug therapy of hyperthyroidism]. The possibilities of the treatment of hyperthyroidism are mentioned, in which cases the author especially deals with the medicamentous therapy, taking into consideration the different chemical groups (imidazol derivations, thiourazil derivations, perchlorates) and their therapeutic mechanisms. The indications and contraindications of this treatment and the possible side effects are compiled in form of a table. The in-vitro-parameters which are necessary for the observation of the course are estimated in their significance. The author deals with the problems of the additional treatment. Taking into consideration indications and contraindications as well as controls of the course of functional parameters the medicamentous therapy concerned is a treatment with a good prognosis. It is promising particularly in such cases, when suitable parameters are used for the solution of the question concerning the end of the therapy. For this purpose nowadays two tests are at our disposal: 1. modified Alexander's test (radioiodine-test and suppression test under thyreostatic therapy) and 2. TRH-test with radioimmunological determination of TSH. The treatment should be carried out in adequate endocrinological dispensaries, as there are certain risks in not optimal therapy."} {"id": "PMID:183394", "title": "[Participation of gonads in pulmonary silicosis].", "content": "A survey is given on the participation of endocrine glands in the pulmonary silicosis. At the same time a new clinical and experimental contribution to the question of the appearance of a hypogonadotropic hypogonadism is given. The frequency of this hypogonadism increases with the severity of the pulmonary silicosis. The immunological opinions as well as the neuroergonal ones concerning the pathogenesis of pulmonary silicosis gave the possibility of a better explanation of the mechanisms, by means of which also other organs may be attacked in pulmonary silicosis. The neuroendocrine system gives a defensive answer to the aggressive silicotic pulmonary process, which in general slowly progresses, but which may also be certain hormones from the group of the glucocorticosteroids in the adrenal cortex. The intervention into the axis hypothalamus-hypophysis-adrenal cortex has been provided in all defence processes of the organism against every aggression. By the functional or organic damage of the neuroendocrine system, by the immediate toxic effect of silicium dioxide or the monosilicium acid as well as by the effect of the secondary hypoxia in pulmonary silicosis an insufficiency in the stimulation and excretion of certain hormones develops. The origin of this insufficiency is found in the hypothalamo-hypophyseal centres, and the effects extend to all endocrine glands which depend on the system hypothalamus-hypophysis. This mechanism is made responsible for the appearance of a hypogonadotropic insufficiency of gonads in the course of a pulmonary silicosis and is proved clinically and experimentally in the cases investigated by the authors", "contents": "[Participation of gonads in pulmonary silicosis]. A survey is given on the participation of endocrine glands in the pulmonary silicosis. At the same time a new clinical and experimental contribution to the question of the appearance of a hypogonadotropic hypogonadism is given. The frequency of this hypogonadism increases with the severity of the pulmonary silicosis. The immunological opinions as well as the neuroergonal ones concerning the pathogenesis of pulmonary silicosis gave the possibility of a better explanation of the mechanisms, by means of which also other organs may be attacked in pulmonary silicosis. The neuroendocrine system gives a defensive answer to the aggressive silicotic pulmonary process, which in general slowly progresses, but which may also be certain hormones from the group of the glucocorticosteroids in the adrenal cortex. The intervention into the axis hypothalamus-hypophysis-adrenal cortex has been provided in all defence processes of the organism against every aggression. By the functional or organic damage of the neuroendocrine system, by the immediate toxic effect of silicium dioxide or the monosilicium acid as well as by the effect of the secondary hypoxia in pulmonary silicosis an insufficiency in the stimulation and excretion of certain hormones develops. The origin of this insufficiency is found in the hypothalamo-hypophyseal centres, and the effects extend to all endocrine glands which depend on the system hypothalamus-hypophysis. This mechanism is made responsible for the appearance of a hypogonadotropic insufficiency of gonads in the course of a pulmonary silicosis and is proved clinically and experimentally in the cases investigated by the authors"} {"id": "PMID:183397", "title": "[Antibody titers--curse in patients with recurring Herpes simplex virus infections under vaccination with heat-inactivated Herpes viruses].", "content": "Follow-up studies of antibody-titres in patients suffering from recidivations of herpes labialis and progenitalis treated with herpes virus vaccine inactivated by heat. It was stated by several authors that patients suffering from recidivations of herpes labialis and progenitalis can be successfully treated with a herpes virus vaccine inactivated by heat (Lupidon G/H). Nothing is known, however, about the mechanisms diminishing recurrences. We have studied 11 patients and 3 control persons whether there were changes in specific antibody titres after repeated vaccinations. Skin reactions following intradermal injections were also tested. Serum samples studied over a period of 8 weeks until 9 months showed that the antibody titres found by complement-fixation and neutralization tests remained practically constant. Skin tests were always negative. Therefore it merits further study to find out the mode of action of this clinically successful treatment.", "contents": "[Antibody titers--curse in patients with recurring Herpes simplex virus infections under vaccination with heat-inactivated Herpes viruses]. Follow-up studies of antibody-titres in patients suffering from recidivations of herpes labialis and progenitalis treated with herpes virus vaccine inactivated by heat. It was stated by several authors that patients suffering from recidivations of herpes labialis and progenitalis can be successfully treated with a herpes virus vaccine inactivated by heat (Lupidon G/H). Nothing is known, however, about the mechanisms diminishing recurrences. We have studied 11 patients and 3 control persons whether there were changes in specific antibody titres after repeated vaccinations. Skin reactions following intradermal injections were also tested. Serum samples studied over a period of 8 weeks until 9 months showed that the antibody titres found by complement-fixation and neutralization tests remained practically constant. Skin tests were always negative. Therefore it merits further study to find out the mode of action of this clinically successful treatment."} {"id": "PMID:183400", "title": "Immunoglobulins under the influence of nonspecific factors. III. Immunoglobulins, pertussis antibodies and lysozyme in three child populations exposed to different air pollution.", "content": "The levels of IgG, IgA, IgM, lysozyme, agglutinins against B. pertussis and B. parapertussis were followed in the blood serum of 306 children 9--10 years old in 3 areas of Central Bohemian region. In children dwelling in areas with more polluted air significantly higher levels of serum lysozyme and of parapertussis antibodies were found by the t-test. The distribution of these values shows significant differences between more polluted areas in comparison with lower-pollution area also in Kolmogorov-Smirnov test. The average levels of Ig approached statistically critical values but did not reach them, but significant differences in the distribution of values of IgG and IgA were shown by the F-test and chi2-test between lightly and heavily polluted areas. The values of immunological reactions in polluted areas were always higher than in the non-polluted group. This provides evidence for a hypothesis about a stimulatory effect of polluted air on immunological mechanisms in child population. The higher values of IgM observed recently by other authors in women were shown in girls of 9--10 years.", "contents": "Immunoglobulins under the influence of nonspecific factors. III. Immunoglobulins, pertussis antibodies and lysozyme in three child populations exposed to different air pollution. The levels of IgG, IgA, IgM, lysozyme, agglutinins against B. pertussis and B. parapertussis were followed in the blood serum of 306 children 9--10 years old in 3 areas of Central Bohemian region. In children dwelling in areas with more polluted air significantly higher levels of serum lysozyme and of parapertussis antibodies were found by the t-test. The distribution of these values shows significant differences between more polluted areas in comparison with lower-pollution area also in Kolmogorov-Smirnov test. The average levels of Ig approached statistically critical values but did not reach them, but significant differences in the distribution of values of IgG and IgA were shown by the F-test and chi2-test between lightly and heavily polluted areas. The values of immunological reactions in polluted areas were always higher than in the non-polluted group. This provides evidence for a hypothesis about a stimulatory effect of polluted air on immunological mechanisms in child population. The higher values of IgM observed recently by other authors in women were shown in girls of 9--10 years."} {"id": "PMID:183401", "title": "Local and systemic opsonic adherent, hemagglutinating and rosette forming activity in mice induced by respiratory immunization with sheep red blood cells.", "content": "The humoral response in mice after intranasal (IN) instillation of sheep red blood cells (SRBC) was compared to that produced by intraperitoneal route of immunization. Study of opsonic adherent (passive indirect cytophilic) and hemagglutinating antibody levels in serum and bronchial washings after repeated challenge with SRBC showed that serum antibody titers following respiratory immunization does not differ from the general pattern of a humoral antibody response. The bronchial wash antibody titer was higher than the serum titer as calculated per globulin unit. In contrast, the appearance of measurable antibodies in the bronchial washings after repeated intraperitoneal immunization was delayed and in low titer. B. pertussis vaccine administered in conjunction with SRBC was found to be an excellent adjuvant in the intranasal route of immunization. A single administration of SRBC-Pertussis evoked a considerable adjuvant effect as measured by hemagglutinating and opsonic adherent tests. Monospecific anti-mouse IgG nullified the hemagglutinating and opsonic adherent activity of the bronchial washings, while monospecific anti-mouse IgM had no effect in either activity. Lung and spleen cells capable of forming rosettes with SRBC of intranasally immunized and control mice were counted. Mean response on day 14 was 6 X 10(3) rosetes per million lung lymphoid cells in comparison with less than 10(3) in control mice. No difference was found in the number of rosette-forming cells in the spleen of control and intranasally immunized mice.", "contents": "Local and systemic opsonic adherent, hemagglutinating and rosette forming activity in mice induced by respiratory immunization with sheep red blood cells. The humoral response in mice after intranasal (IN) instillation of sheep red blood cells (SRBC) was compared to that produced by intraperitoneal route of immunization. Study of opsonic adherent (passive indirect cytophilic) and hemagglutinating antibody levels in serum and bronchial washings after repeated challenge with SRBC showed that serum antibody titers following respiratory immunization does not differ from the general pattern of a humoral antibody response. The bronchial wash antibody titer was higher than the serum titer as calculated per globulin unit. In contrast, the appearance of measurable antibodies in the bronchial washings after repeated intraperitoneal immunization was delayed and in low titer. B. pertussis vaccine administered in conjunction with SRBC was found to be an excellent adjuvant in the intranasal route of immunization. A single administration of SRBC-Pertussis evoked a considerable adjuvant effect as measured by hemagglutinating and opsonic adherent tests. Monospecific anti-mouse IgG nullified the hemagglutinating and opsonic adherent activity of the bronchial washings, while monospecific anti-mouse IgM had no effect in either activity. Lung and spleen cells capable of forming rosettes with SRBC of intranasally immunized and control mice were counted. Mean response on day 14 was 6 X 10(3) rosetes per million lung lymphoid cells in comparison with less than 10(3) in control mice. No difference was found in the number of rosette-forming cells in the spleen of control and intranasally immunized mice."} {"id": "PMID:183402", "title": "Identification of collagen-anticollagen immune complexes by collagenase-digestion.", "content": "A method for the detection of collagen-anti-collagen immune complexes using collagenase of bacterial origin is described. Anti-collagen-titers are determined in passive haemagglutination before and after collagenase digestion of samples containing preformed immune complexes. An increase in anti-collagen titers following the enzymatic treatment suggests the presence of collagen-anti-collagen immune complexes. Both solbule and carrier-bound collagenase proved to be equally effective in the digestion of complex-bound collagen, if in vitro prepared collagen-anti-collagen complexes were investigated. Original titers of partially or totally inhibited antisera to collagen could be completely restored by this method.", "contents": "Identification of collagen-anticollagen immune complexes by collagenase-digestion. A method for the detection of collagen-anti-collagen immune complexes using collagenase of bacterial origin is described. Anti-collagen-titers are determined in passive haemagglutination before and after collagenase digestion of samples containing preformed immune complexes. An increase in anti-collagen titers following the enzymatic treatment suggests the presence of collagen-anti-collagen immune complexes. Both solbule and carrier-bound collagenase proved to be equally effective in the digestion of complex-bound collagen, if in vitro prepared collagen-anti-collagen complexes were investigated. Original titers of partially or totally inhibited antisera to collagen could be completely restored by this method."} {"id": "PMID:183404", "title": "Indirect EPR evidence for the production of singlet oxygen in the photosensitization of nucleic acid constituents by proflavine.", "content": "EPR spectroscopy is used to analyse the influence of D2O and NaN3 on the free radicals induced in frozen aqueous solutions of 5'-thymidine monophosphate photosensitized (lambda greater than 320 nm) by proflavine at 205 K. The results can be explained if the production of singlet oxygen during the process is assumed.", "contents": "Indirect EPR evidence for the production of singlet oxygen in the photosensitization of nucleic acid constituents by proflavine. EPR spectroscopy is used to analyse the influence of D2O and NaN3 on the free radicals induced in frozen aqueous solutions of 5'-thymidine monophosphate photosensitized (lambda greater than 320 nm) by proflavine at 205 K. The results can be explained if the production of singlet oxygen during the process is assumed."} {"id": "PMID:183411", "title": "[Hidradenoma of the skin. Synoptic reveiw of syringeal hidradenoma, eccrine epithelioma and eccrine basalioma (author's transl)].", "content": "An ulcerating and sclerosing skin tumour on the temporal forehead region is described. Histologically the tumour is composed of different structures as cystic hidradenoma, syringoma, ductal hidradenoma and sclerres as cystic hidradenoma, syringoma, ductal hidradenoma and sclerosing basalioma arranged in layers. The tumour appears to be a distinct and diagnosable entity. It exists a major similarity to such tumours reported as syringeal hidradenoma, eccrine epithelioma or eccrine basalioma.", "contents": "[Hidradenoma of the skin. Synoptic reveiw of syringeal hidradenoma, eccrine epithelioma and eccrine basalioma (author's transl)]. An ulcerating and sclerosing skin tumour on the temporal forehead region is described. Histologically the tumour is composed of different structures as cystic hidradenoma, syringoma, ductal hidradenoma and sclerres as cystic hidradenoma, syringoma, ductal hidradenoma and sclerosing basalioma arranged in layers. The tumour appears to be a distinct and diagnosable entity. It exists a major similarity to such tumours reported as syringeal hidradenoma, eccrine epithelioma or eccrine basalioma."} {"id": "PMID:183408", "title": "Coupling factor adenosine-5'-triphosphatase from Rhodospirillum rubrum: a simple and rapid procedure for its purification.", "content": "When photosynthetic membranes from Rhodospirillum rubrum, devoid of loosely bound small molecules and proteins, were passed through a French-pressure cell, the enzyme adenosine-5'-triphosphatase (EC 3.6.1.3.) (ATPase) was released into the soluble fraction. The solubilized ATPase was purified to homogeneity. In many respects it behaved like the enzyme purified by other workers, but it also hydrolyzed Mg-ATP with a small, but significant rate. Furthermore, it was much more stable. Maximal restoration of photophosphorylation in ATPase-depleted membranes was achieved by addition of about 1 mg purified ATPase per mg bacteriochlorophyll. For reconstitution of NAD+-photoreduction, about half of this amount was saturating.", "contents": "Coupling factor adenosine-5'-triphosphatase from Rhodospirillum rubrum: a simple and rapid procedure for its purification. When photosynthetic membranes from Rhodospirillum rubrum, devoid of loosely bound small molecules and proteins, were passed through a French-pressure cell, the enzyme adenosine-5'-triphosphatase (EC 3.6.1.3.) (ATPase) was released into the soluble fraction. The solubilized ATPase was purified to homogeneity. In many respects it behaved like the enzyme purified by other workers, but it also hydrolyzed Mg-ATP with a small, but significant rate. Furthermore, it was much more stable. Maximal restoration of photophosphorylation in ATPase-depleted membranes was achieved by addition of about 1 mg purified ATPase per mg bacteriochlorophyll. For reconstitution of NAD+-photoreduction, about half of this amount was saturating."} {"id": "PMID:183413", "title": "[Indications and technics for esophagoduodenostomy].", "content": "From 1961 to 1974 19 esophagoduodenostomies have been performed after total gastrectomy. One patient died postoperatively because of pulmonary embolism. The mean survival rate was 16,4 months. In far advanced gastric carcinomas an elongation and dilatation of the duodenum favours this kind of anastomosis. In low risk patients, in the aged and for palliative gastrectomy we suggest to prove the possibility for performing an esophagoduodenostomy.", "contents": "[Indications and technics for esophagoduodenostomy]. From 1961 to 1974 19 esophagoduodenostomies have been performed after total gastrectomy. One patient died postoperatively because of pulmonary embolism. The mean survival rate was 16,4 months. In far advanced gastric carcinomas an elongation and dilatation of the duodenum favours this kind of anastomosis. In low risk patients, in the aged and for palliative gastrectomy we suggest to prove the possibility for performing an esophagoduodenostomy."} {"id": "PMID:183414", "title": "[Arrhenoblastoma with following pregnancy].", "content": "The emergence, the morphology, the characteristic symptoms, the treatment and prognosis of a rare tumour of the ovary, arrhenoblastoma, is dealt with in this article. This is followed by the writer's own experience of the case of a 24 year old patient who had a normal pregnancy and birth 2 years after the existirpation of a tumour on the left side, which, having been detected by change, proved to be a non-malignant arrhenoblastoma. The symptoms of virilism so typical of the tumour had disappeared. The normal female characteristics had returned. The patient has now been free of symptoms for 10 years. In cases of increasing virilism differential diagnostics should consider the possibility of this rare tumour.", "contents": "[Arrhenoblastoma with following pregnancy]. The emergence, the morphology, the characteristic symptoms, the treatment and prognosis of a rare tumour of the ovary, arrhenoblastoma, is dealt with in this article. This is followed by the writer's own experience of the case of a 24 year old patient who had a normal pregnancy and birth 2 years after the existirpation of a tumour on the left side, which, having been detected by change, proved to be a non-malignant arrhenoblastoma. The symptoms of virilism so typical of the tumour had disappeared. The normal female characteristics had returned. The patient has now been free of symptoms for 10 years. In cases of increasing virilism differential diagnostics should consider the possibility of this rare tumour."} {"id": "PMID:183409", "title": "Synthesis and electron spin resonance study of spin-labelled compounds related to tumour-growth inhibitory nitroarylaziridines.", "content": "Three stable free radicals have been prepared which are akin to 5-aziridino-2,4-dinitrobenzamide (CB 1954); these compounds all contain a nitroxide function. The metabolism and excretion of two such compounds in mice has been monitored by electron spin resonance (ESR) spectroscopy and compared with that of the simpler nitroxide, 4-keto-2,2,6,6-tetramethylpiperidino-1-oxyl (tempone).", "contents": "Synthesis and electron spin resonance study of spin-labelled compounds related to tumour-growth inhibitory nitroarylaziridines. Three stable free radicals have been prepared which are akin to 5-aziridino-2,4-dinitrobenzamide (CB 1954); these compounds all contain a nitroxide function. The metabolism and excretion of two such compounds in mice has been monitored by electron spin resonance (ESR) spectroscopy and compared with that of the simpler nitroxide, 4-keto-2,2,6,6-tetramethylpiperidino-1-oxyl (tempone)."} {"id": "PMID:183410", "title": "MO calculations of some thymine radicals at the INDO level.", "content": "The results of MO INDO calculations of some thymine radicals are presented. These include as well as the hydrogen addition radicals the hydroxyl addition radicals to C5 and to C6 of the C5=C6 double bond of the thymine molecule. The radicals resulting from hydrogen abstraction from the methyl group and from the nitrogen N1 are also studied. Except for radicals where the main spin density is localized on nitrogen atoms, the agreement between experimental and theoretical couplings is satisfactory.", "contents": "MO calculations of some thymine radicals at the INDO level. The results of MO INDO calculations of some thymine radicals are presented. These include as well as the hydrogen addition radicals the hydroxyl addition radicals to C5 and to C6 of the C5=C6 double bond of the thymine molecule. The radicals resulting from hydrogen abstraction from the methyl group and from the nitrogen N1 are also studied. Except for radicals where the main spin density is localized on nitrogen atoms, the agreement between experimental and theoretical couplings is satisfactory."} {"id": "PMID:183428", "title": "[Ultrastructure of B. pertussis using cryoultramicrotomy].", "content": "The authors pointed to a possibility of using the method of cryoultramicrotomy in studying the ultrastructure of Gram negative B. pertussis bacteria under the following conditions: a) fixationwith a 5% glutaraldehyde on cacodylate buffer (pH 7.5) for 30 min; b) replacement with a 30% dimethylsulfoxide in distilled water with a subsequent embedding of the material into tissue-tek; c) freezing in fluid nitrogen for 5 min; d) cutting at a temperature of -- 90% degrees C and at the temperature of glass knife of -- 40 degrees C, the knife angle of alpha = 45 degrees, beta = 6 degrees, and the cutting velocity of 5 mm/sec; e) placing of sections on copper grates covered with a 0.1% moulding membrane; d) contrasting with a 2% phosphotungstic acid queous solution (pH 7.5) for 5 sec and with a 3% uranil acetate on water for 5 min. Use of the mentioned method pemitted to detect structures localized in B. pertussis cytoplasm and also to trace the dynamics of their formation.", "contents": "[Ultrastructure of B. pertussis using cryoultramicrotomy]. The authors pointed to a possibility of using the method of cryoultramicrotomy in studying the ultrastructure of Gram negative B. pertussis bacteria under the following conditions: a) fixationwith a 5% glutaraldehyde on cacodylate buffer (pH 7.5) for 30 min; b) replacement with a 30% dimethylsulfoxide in distilled water with a subsequent embedding of the material into tissue-tek; c) freezing in fluid nitrogen for 5 min; d) cutting at a temperature of -- 90% degrees C and at the temperature of glass knife of -- 40 degrees C, the knife angle of alpha = 45 degrees, beta = 6 degrees, and the cutting velocity of 5 mm/sec; e) placing of sections on copper grates covered with a 0.1% moulding membrane; d) contrasting with a 2% phosphotungstic acid queous solution (pH 7.5) for 5 sec and with a 3% uranil acetate on water for 5 min. Use of the mentioned method pemitted to detect structures localized in B. pertussis cytoplasm and also to trace the dynamics of their formation."} {"id": "PMID:183429", "title": "[Comparative characteristics of antigenic peculiarities and several other properties of stable long-term cultures of salmonella L-forms].", "content": "Enzymatic properties, sensitivity to antibiotics and peculiarities of the antigenic structure of stable L-forms of S. paratyphi B (L-115), S. typhimurium (L-71a-16) and S. typhi (L-5761) were studied. In difference from the initial strains, the L-form under study possessed a high penicillin and ampicillin sensitivity, and also a marked sensitivity to polymyxin and detergents; this characterized them as L-forms of protoplastic type. All the L-variants differed considerably by the enzymatic properties from the initial strains, and, in the majority of cases, retained the antigenic components and the species-specificity characteristic of the initial parental cultures. Despite the loss of the cell wall the synthesis of O-antigen in the L-forms under study was undisturbed. The 6-forms contained an antigenic component not found in the initial cultures and apparently causing the neutralizing activity of the L-antiser.", "contents": "[Comparative characteristics of antigenic peculiarities and several other properties of stable long-term cultures of salmonella L-forms]. Enzymatic properties, sensitivity to antibiotics and peculiarities of the antigenic structure of stable L-forms of S. paratyphi B (L-115), S. typhimurium (L-71a-16) and S. typhi (L-5761) were studied. In difference from the initial strains, the L-form under study possessed a high penicillin and ampicillin sensitivity, and also a marked sensitivity to polymyxin and detergents; this characterized them as L-forms of protoplastic type. All the L-variants differed considerably by the enzymatic properties from the initial strains, and, in the majority of cases, retained the antigenic components and the species-specificity characteristic of the initial parental cultures. Despite the loss of the cell wall the synthesis of O-antigen in the L-forms under study was undisturbed. The 6-forms contained an antigenic component not found in the initial cultures and apparently causing the neutralizing activity of the L-antiser."} {"id": "PMID:183430", "title": "[Morphology of Halprowia (Chlamydia) isolated in Reiter's syndrome].", "content": "Morphology and ultrastructure of Halprowia arthritidis, strain SR-1 (HSR), isolated from the synovial fluid of a patient with Reiter's syndrome, was studied in the membranes of the yolk sacs of the developing chick embryos and the L-cell culture. In acridine orange staining for light and fluorescent microscopy there was revealed intracellular cytoplasmic inclusions containing HSR structures at various stages of its reproduction characteristic of halprowia (chlamydia). The direct immunofluorescent method demonstrated the presence of a characteristic HSR antigen not only in the developed inclusions, but also at the early stages of infection, when the morphological HSR structures could not be found by light microscopy. The ultrastructure of the HSR inclusions and forms in the cycle of development (of the initial and elementary bodies) of the SR-1 strain was typical of other halprowia. A peculiar structure of a complex of cell wall and cytoplasmic membrane of the elementary body was described. Taking into consideration the biological characteristics of HSR revealed earlier it can be considered to be a typical representative of Halprowiales s. Chlamydiales. The data obtained on other halprowia, pointing out the fact that criteria of compactness and diffuseness of inclusions, the presence of absence of glycogen in the inclusions could not serve as taxonomic signs in classification of halrpowia, were confirmed on a model of the SR-1 studied.", "contents": "[Morphology of Halprowia (Chlamydia) isolated in Reiter's syndrome]. Morphology and ultrastructure of Halprowia arthritidis, strain SR-1 (HSR), isolated from the synovial fluid of a patient with Reiter's syndrome, was studied in the membranes of the yolk sacs of the developing chick embryos and the L-cell culture. In acridine orange staining for light and fluorescent microscopy there was revealed intracellular cytoplasmic inclusions containing HSR structures at various stages of its reproduction characteristic of halprowia (chlamydia). The direct immunofluorescent method demonstrated the presence of a characteristic HSR antigen not only in the developed inclusions, but also at the early stages of infection, when the morphological HSR structures could not be found by light microscopy. The ultrastructure of the HSR inclusions and forms in the cycle of development (of the initial and elementary bodies) of the SR-1 strain was typical of other halprowia. A peculiar structure of a complex of cell wall and cytoplasmic membrane of the elementary body was described. Taking into consideration the biological characteristics of HSR revealed earlier it can be considered to be a typical representative of Halprowiales s. Chlamydiales. The data obtained on other halprowia, pointing out the fact that criteria of compactness and diffuseness of inclusions, the presence of absence of glycogen in the inclusions could not serve as taxonomic signs in classification of halrpowia, were confirmed on a model of the SR-1 studied."} {"id": "PMID:183431", "title": "[Discharge of myeloperoxidase from neutrophils during bacterial sorption].", "content": "A study was made of conditions and dynamics of discharge of myeloperoxidase (MPO) from rabbit neutrophils in case of encounter with staphylococci. The discharge began not later than 9--12 minutes after the administration of Staph. aureus into the neutrophil suspension, i. e. as early as the stage of bacterial sorption, and reached the maximum by the 30th minute. The contact of neutrophils with individual bacteria was an adequate signal for the beginning of the discharge. The greatest discharge was with the ratio of 5 bacteria per one neutrophil. The discharge was retarded when this ratio reached 80: 1. A hypothesis on the \"avalanche\" switchingon of the system of MPO discharge: a single bacteria injection mu/ml a discharge from an individual neutrophil of MPO and cation proteins; the latter switch on discharge from several other neutrophils, without any participation of bacteria. Cation proteins intensified the MPO discharge in the concentration of the 10--20 switch on. Biolgical significance of the phenomenon of early discharge of antibacterial factors no directed to the provision of phagocytosis is discussed.", "contents": "[Discharge of myeloperoxidase from neutrophils during bacterial sorption]. A study was made of conditions and dynamics of discharge of myeloperoxidase (MPO) from rabbit neutrophils in case of encounter with staphylococci. The discharge began not later than 9--12 minutes after the administration of Staph. aureus into the neutrophil suspension, i. e. as early as the stage of bacterial sorption, and reached the maximum by the 30th minute. The contact of neutrophils with individual bacteria was an adequate signal for the beginning of the discharge. The greatest discharge was with the ratio of 5 bacteria per one neutrophil. The discharge was retarded when this ratio reached 80: 1. A hypothesis on the \"avalanche\" switchingon of the system of MPO discharge: a single bacteria injection mu/ml a discharge from an individual neutrophil of MPO and cation proteins; the latter switch on discharge from several other neutrophils, without any participation of bacteria. Cation proteins intensified the MPO discharge in the concentration of the 10--20 switch on. Biolgical significance of the phenomenon of early discharge of antibacterial factors no directed to the provision of phagocytosis is discussed."} {"id": "PMID:183432", "title": "Insulomas and multiple endocrine neoplasia.", "content": "Seventy-eight patients with insuloma diagnosed between 1959 and 1968 in Sweden were studied for neoplasia in other organs. Twenty-one patients had beta-cell islet tumors, 14 Zollinger-Ellison's syndrome and non-beta-cell islet tumors, while no endocrine activity was demonstrated in 43 patients. Of the last-mentioned group, 9 patients had co-existing disease of other endocrine organs. In 10 patients, non-endocrine organs were found to be affected by malignant diseases. It appears probable that the tissue of the pancreatic islets, like parathyroid tissue, can react with hyperplasia with a later development of adenoma, secondary to tumors in other organs.", "contents": "Insulomas and multiple endocrine neoplasia. Seventy-eight patients with insuloma diagnosed between 1959 and 1968 in Sweden were studied for neoplasia in other organs. Twenty-one patients had beta-cell islet tumors, 14 Zollinger-Ellison's syndrome and non-beta-cell islet tumors, while no endocrine activity was demonstrated in 43 patients. Of the last-mentioned group, 9 patients had co-existing disease of other endocrine organs. In 10 patients, non-endocrine organs were found to be affected by malignant diseases. It appears probable that the tissue of the pancreatic islets, like parathyroid tissue, can react with hyperplasia with a later development of adenoma, secondary to tumors in other organs."} {"id": "PMID:183433", "title": "The unique cytologic picture of oat cell carcinoma in effusions.", "content": "Characteristic and unique patterns of the tumor cell population in pleural effusions in oat cell carcinoma have been described in detail. This pattern is constituted by rows of tumor cells or cell layers forming \"vertebrae like\" figures and \"onion like\" formations. A distinct pattern of this kind was only found in oat cell carcinoma. A distinct \"oat cell carcinoma pattern\" was also found in one quarter of the patients in a series of oat cell cancer with cytologic analysis of sputum. This fact may be of importance for the accurate typing of small cell undifferentiated cancer in sputum and bronchial secretions. Identical formations were also found in a histologic series of oat cell cancer. The study indicates that in small cell carcinoma of the lung it is possible by cytologic analysis of positive effusions not only to make a diagnosis of carcinoma, but also to confirm the histologic type and, thus, the origin of the tumor.", "contents": "The unique cytologic picture of oat cell carcinoma in effusions. Characteristic and unique patterns of the tumor cell population in pleural effusions in oat cell carcinoma have been described in detail. This pattern is constituted by rows of tumor cells or cell layers forming \"vertebrae like\" figures and \"onion like\" formations. A distinct pattern of this kind was only found in oat cell carcinoma. A distinct \"oat cell carcinoma pattern\" was also found in one quarter of the patients in a series of oat cell cancer with cytologic analysis of sputum. This fact may be of importance for the accurate typing of small cell undifferentiated cancer in sputum and bronchial secretions. Identical formations were also found in a histologic series of oat cell cancer. The study indicates that in small cell carcinoma of the lung it is possible by cytologic analysis of positive effusions not only to make a diagnosis of carcinoma, but also to confirm the histologic type and, thus, the origin of the tumor."} {"id": "PMID:183434", "title": "Cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma.", "content": "In order to estimate the possibility of a cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma, 121 histologically proven cases of these two types of lung cancer were studied. Certain features of the tumor cells were used as differential diagnostic parameters. By means of these features it was possible to correctly type 90% of the bronchiolo-alveolar carcinomas and 72% of the bronchogenic adenocarcinomas. The most striking characteristics of bronchiolo-alveolar carcinoma was the uniformity of cells, the occurrence of such cells in tightly packed clusters, the absence of prominent nucleoli and also the scarcity of single tumor cells. Thus, it seems possible to make a correct cytologic differential diagnosis between these two types of lung tumors with high accuracy.", "contents": "Cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma. In order to estimate the possibility of a cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma, 121 histologically proven cases of these two types of lung cancer were studied. Certain features of the tumor cells were used as differential diagnostic parameters. By means of these features it was possible to correctly type 90% of the bronchiolo-alveolar carcinomas and 72% of the bronchogenic adenocarcinomas. The most striking characteristics of bronchiolo-alveolar carcinoma was the uniformity of cells, the occurrence of such cells in tightly packed clusters, the absence of prominent nucleoli and also the scarcity of single tumor cells. Thus, it seems possible to make a correct cytologic differential diagnosis between these two types of lung tumors with high accuracy."} {"id": "PMID:183435", "title": "Evaluation of needle aspirates and tissue sections as prognostic factors in mammary carcinoma.", "content": "The prognostic influence in operable mammary carcinoma of morphologic predictors evaluated in smears of needle-biopsy aspirate and in tissue sections and of clinical stage was investigated. Size of nuclei in smears of aspirate was found to convey prognostic information of the same order of importance as the variables tubule information and mitotic frequency in tissue sections. The combination of clinical stage with variables in smears and in sections enhanced the explanatory value.", "contents": "Evaluation of needle aspirates and tissue sections as prognostic factors in mammary carcinoma. The prognostic influence in operable mammary carcinoma of morphologic predictors evaluated in smears of needle-biopsy aspirate and in tissue sections and of clinical stage was investigated. Size of nuclei in smears of aspirate was found to convey prognostic information of the same order of importance as the variables tubule information and mitotic frequency in tissue sections. The combination of clinical stage with variables in smears and in sections enhanced the explanatory value."} {"id": "PMID:183436", "title": "Oncornavirus-like particles in biopsy material from a glandular erosion of the human uterine cervix.", "content": "Virus-like particles have been detected electron microscopically in biopsy material from a glandular erosion of the human uterine cervix. Morphologically, the particles resemble immature and mature type C virus particles. The significance of the oncornavirus-like structures remains unknown.", "contents": "Oncornavirus-like particles in biopsy material from a glandular erosion of the human uterine cervix. Virus-like particles have been detected electron microscopically in biopsy material from a glandular erosion of the human uterine cervix. Morphologically, the particles resemble immature and mature type C virus particles. The significance of the oncornavirus-like structures remains unknown."} {"id": "PMID:183441", "title": "Different effects of exogenous cyclic adenosine monophosphate and its dibutryl derivative on plasma growth hormone, glucose, insulin and cortisol.", "content": "The effects of the infusion in four different dosages (0.001, 0.005, 0.02 and 0.2 mg/kg/min during 60 min) of cyclic 3',5'-adenosine monophosphate and of its dibutyryl derivative on plasma growth hormone and on glucose, immunoreactive insulin and cortisol were studied in 38 normal subjects and in 10 patients with idiopathic hypopituitarism. In normal subjects cyclic 3',5'-adenosine monophosphate provokes an increase in plasma growth hormone levels (only when a dosage of 0.2 mg/kg/min is used) without any changes in plasma glucose, insulin and cortisol. The maximal value of the means is observed 75 min after starting the infusion. Dibutyryl cyclic 3',5'-adenosine monophosphate (0.2 and 0.02 mg/kg/min) provokes a dose-related rise in plasma growth hormone levels which is always preceded by hyperglycaemia and hyperinsulinaemia. The peak of the mean growth hormone levels occurs at 135 min after initiation of the infusion. In all but one hypopituitary patients the nucleotides do not promote growth hormone secretion. It is concluded that exogenous cyclic 3',5'-adenosine monophosphate and its dibutyryl derivative may not be considered as analogous and that both compounds may contribute to study growth hormone release in normal subjects and in patients with growth abnormalities.", "contents": "Different effects of exogenous cyclic adenosine monophosphate and its dibutryl derivative on plasma growth hormone, glucose, insulin and cortisol. The effects of the infusion in four different dosages (0.001, 0.005, 0.02 and 0.2 mg/kg/min during 60 min) of cyclic 3',5'-adenosine monophosphate and of its dibutyryl derivative on plasma growth hormone and on glucose, immunoreactive insulin and cortisol were studied in 38 normal subjects and in 10 patients with idiopathic hypopituitarism. In normal subjects cyclic 3',5'-adenosine monophosphate provokes an increase in plasma growth hormone levels (only when a dosage of 0.2 mg/kg/min is used) without any changes in plasma glucose, insulin and cortisol. The maximal value of the means is observed 75 min after starting the infusion. Dibutyryl cyclic 3',5'-adenosine monophosphate (0.2 and 0.02 mg/kg/min) provokes a dose-related rise in plasma growth hormone levels which is always preceded by hyperglycaemia and hyperinsulinaemia. The peak of the mean growth hormone levels occurs at 135 min after initiation of the infusion. In all but one hypopituitary patients the nucleotides do not promote growth hormone secretion. It is concluded that exogenous cyclic 3',5'-adenosine monophosphate and its dibutyryl derivative may not be considered as analogous and that both compounds may contribute to study growth hormone release in normal subjects and in patients with growth abnormalities."} {"id": "PMID:183437", "title": "Pulmonary blastoma: cytopathologic and histopathologic findings.", "content": "A case of pulmonary blastoma has been presented with a description of the pulmonary cytology and review of the literature. Recognition of the two cell patterns of the tumor, carcinomatous and sarcomatous elements, in the cytologic specimen may lead one to the correct diagnosis of a mixed tumor. Ferruginous bodies and microliths were also associated in this case.", "contents": "Pulmonary blastoma: cytopathologic and histopathologic findings. A case of pulmonary blastoma has been presented with a description of the pulmonary cytology and review of the literature. Recognition of the two cell patterns of the tumor, carcinomatous and sarcomatous elements, in the cytologic specimen may lead one to the correct diagnosis of a mixed tumor. Ferruginous bodies and microliths were also associated in this case."} {"id": "PMID:183442", "title": "Demonstration of a pituitary gonadotrophin hormone activity in the male foetal mouse.", "content": "The testosterone production by 18-days-old foetal mouse testis was measured in an organ culture system, by RIA in the culture medium. This production was time-dependent, and could be stimulated by ovine LH and age-matched foetal pituitary. The gonadotrophin activity derived from foetal pituitary appeared to be released into the culture medium as a limited reserve. These data clearly show that a biologically active gonadotrophin material is present in the pituitary of the 18-days-old mouse foetus.", "contents": "Demonstration of a pituitary gonadotrophin hormone activity in the male foetal mouse. The testosterone production by 18-days-old foetal mouse testis was measured in an organ culture system, by RIA in the culture medium. This production was time-dependent, and could be stimulated by ovine LH and age-matched foetal pituitary. The gonadotrophin activity derived from foetal pituitary appeared to be released into the culture medium as a limited reserve. These data clearly show that a biologically active gonadotrophin material is present in the pituitary of the 18-days-old mouse foetus."} {"id": "PMID:183443", "title": "Comparison of circulating glycoprotein hormones and their subunits in patients with oat cell carcinoma of the lung and uraemic patients on chronic dialysis.", "content": "It has recently been suggested that the measurement of the glycoprotein hormones and their subunits in human serum may serve as biochemical markers of non-endocrine tumours. Using radioimmunoassays for LH, FSH, HCGbeta-, LHbeta- and the common alpha-subunit, significant differences in the levels of these substances could not be detected between patients with oat cell lung tumours and patients with chronic renal failure. However, compared to normal subjects the alpha-subunit levels in serum were elevated in 12% of the male and 30% of the female patients with oat cell carcinoma of the lund and in 80 and 50% of the male and female patients, respectively, with chronic renal failure. The LHbeta-subunit concentration was normal in all tumour patients and none of these patients had detectable (less than 4 ng/ml) levels of HCGbeta-subunit. While such measurements may be of value in relationship to particular neoplasms, it appears that raised levels of glycoproteins and their subunits may be found in other disease states.", "contents": "Comparison of circulating glycoprotein hormones and their subunits in patients with oat cell carcinoma of the lung and uraemic patients on chronic dialysis. It has recently been suggested that the measurement of the glycoprotein hormones and their subunits in human serum may serve as biochemical markers of non-endocrine tumours. Using radioimmunoassays for LH, FSH, HCGbeta-, LHbeta- and the common alpha-subunit, significant differences in the levels of these substances could not be detected between patients with oat cell lung tumours and patients with chronic renal failure. However, compared to normal subjects the alpha-subunit levels in serum were elevated in 12% of the male and 30% of the female patients with oat cell carcinoma of the lund and in 80 and 50% of the male and female patients, respectively, with chronic renal failure. The LHbeta-subunit concentration was normal in all tumour patients and none of these patients had detectable (less than 4 ng/ml) levels of HCGbeta-subunit. While such measurements may be of value in relationship to particular neoplasms, it appears that raised levels of glycoproteins and their subunits may be found in other disease states."} {"id": "PMID:183444", "title": "Pituitary-thyroid interrelationship in rats exposed to different environmental temperatures.", "content": "The present work intended to show interrelationships between triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and cyclic adenosine 3'5'-monophosphate (cyclic AMP) in both the pituitary and the thyroid. Experiments were carried out on animals exposed to 0 and 37 degrees C for 4 days and to 34 degrees C for 21 days. Control animals were maintained at 22 degrees C. T4 serum levels of 2.6, 4.0 1.1 and 0.42 mug/100 ml serum, and T3 levels of 95, 135, 65 and 36 ng/100 ml serum were recorded at 22, 0, 34 and 37 degrees C, respectively. The observed serum TSH levels were 265, 192, 237 and 182 mug/100 ml serum in rats exposed to 22, 0, 34 and 37 degrees C, respectively. Pituitary TSH content was similar at 22, 0 and 34 degrees C whereas the content in the 37 degrees C exposed rats was twice that of controls. Thyroid cyclic AMP levels were not significantly different among the various experimental groups. The content of cyclic AMP in the pituitary was higher at 34 degrees C by 125% and 37 degrees C by 240%, and lower at 0 degress C by 56% with regard to the control. These results suggest that the 0 and 34 degrees C exposed rats reach a new steady state in the control of thyroid hormones secretion rate. However, at 37 degrees C, the TSH-Thyroxine interrelationships seem to break down.", "contents": "Pituitary-thyroid interrelationship in rats exposed to different environmental temperatures. The present work intended to show interrelationships between triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and cyclic adenosine 3'5'-monophosphate (cyclic AMP) in both the pituitary and the thyroid. Experiments were carried out on animals exposed to 0 and 37 degrees C for 4 days and to 34 degrees C for 21 days. Control animals were maintained at 22 degrees C. T4 serum levels of 2.6, 4.0 1.1 and 0.42 mug/100 ml serum, and T3 levels of 95, 135, 65 and 36 ng/100 ml serum were recorded at 22, 0, 34 and 37 degrees C, respectively. The observed serum TSH levels were 265, 192, 237 and 182 mug/100 ml serum in rats exposed to 22, 0, 34 and 37 degrees C, respectively. Pituitary TSH content was similar at 22, 0 and 34 degrees C whereas the content in the 37 degrees C exposed rats was twice that of controls. Thyroid cyclic AMP levels were not significantly different among the various experimental groups. The content of cyclic AMP in the pituitary was higher at 34 degrees C by 125% and 37 degrees C by 240%, and lower at 0 degress C by 56% with regard to the control. These results suggest that the 0 and 34 degrees C exposed rats reach a new steady state in the control of thyroid hormones secretion rate. However, at 37 degrees C, the TSH-Thyroxine interrelationships seem to break down."} {"id": "PMID:183447", "title": "Cells of the adenohypophysis of the mink (Mustela vison) identified by immunohistochemical and functional criteria.", "content": "Six cell types were described in the adenohypophysis of the mink, and a putative function was assigned to each type. These cells are the two types of gonadotrophic cells, a thyrotrophic hormone (TSH) cell, a somatotrophic (STH) cell, a prolactin (PRL) cell and a corticotrophin-producing (ACTH) cell. Gonadotrophic cells were identified by an immunolocalization technique using antisera to ovine LH. TSH cells and ACTH cells were identified by ablation of respective target organs and observation of the subsequent hypertrophic cells in the pituitary, as well as comparison with published descriptions in other species. STH cells were identified by comparison with published reports. PRL cells were observed in lactating animals and animals in lactational withdrawal.", "contents": "Cells of the adenohypophysis of the mink (Mustela vison) identified by immunohistochemical and functional criteria. Six cell types were described in the adenohypophysis of the mink, and a putative function was assigned to each type. These cells are the two types of gonadotrophic cells, a thyrotrophic hormone (TSH) cell, a somatotrophic (STH) cell, a prolactin (PRL) cell and a corticotrophin-producing (ACTH) cell. Gonadotrophic cells were identified by an immunolocalization technique using antisera to ovine LH. TSH cells and ACTH cells were identified by ablation of respective target organs and observation of the subsequent hypertrophic cells in the pituitary, as well as comparison with published descriptions in other species. STH cells were identified by comparison with published reports. PRL cells were observed in lactating animals and animals in lactational withdrawal."} {"id": "PMID:183448", "title": "[Functional morphology of the theca interna of the vesicular follicle in human ovary].", "content": "A study of histological serial sections of human ovaries and histochemical reactions established that several cell types differentiate in the theca interna during the formation and development of tertiary follicles (2nd growth period). This leads, in turn, to triple-layering of the theca interna in follicles of the 2nd resting period. The inner thecal layer consists of fusiform cells from the basement membrane, which are apposed to the membrana granulosa and show a strong positive reaction to alkaline phosphatases. A tropic function for the follicular epithelium must be assigned to this layer. The middle layer consists of epitheloid thecal cells, which show a strong positive reaction to 3beta-ol-steroid hydrogenase. These represent the estrogen glands of the follicle. The outer layer of the theca interna, whose transition to the theca externa is indistinct, also has fusiform cells, which are available as reserve material for the differentiation of further epitheloid thecal cells to pre-ovulatory follicles in later periods of development.", "contents": "[Functional morphology of the theca interna of the vesicular follicle in human ovary]. A study of histological serial sections of human ovaries and histochemical reactions established that several cell types differentiate in the theca interna during the formation and development of tertiary follicles (2nd growth period). This leads, in turn, to triple-layering of the theca interna in follicles of the 2nd resting period. The inner thecal layer consists of fusiform cells from the basement membrane, which are apposed to the membrana granulosa and show a strong positive reaction to alkaline phosphatases. A tropic function for the follicular epithelium must be assigned to this layer. The middle layer consists of epitheloid thecal cells, which show a strong positive reaction to 3beta-ol-steroid hydrogenase. These represent the estrogen glands of the follicle. The outer layer of the theca interna, whose transition to the theca externa is indistinct, also has fusiform cells, which are available as reserve material for the differentiation of further epitheloid thecal cells to pre-ovulatory follicles in later periods of development."} {"id": "PMID:183449", "title": "Histochemistry of normal and diseased human lymph nodes.", "content": "Gomori's metal precipitate technique was used to demonstrate the phosphatase activity of the human cervical lymph node in health and disease, using four different phosphate esters (sodium beta-glycerophosphate and adenosine triphosphate at pH 9, riboflavin 5'-phosphate at pH 9.2 and 5'-monophosphoric acid at pH 8.3). In fetal lymph nodes, using 5'-monophosphoric acid, an outstanding positive activity was noticed in the lymphatic follicles. With the other three substrates there was either no nodular reaction or just a narrow rim of positive activity around the follicles, the internodular tissue being negative with all four substrates used. With chronic non-specific lymphadenitis the enzyme hydrolysing the three substrates (beta-glycerophosphate, riboflavin 5'-phosphate and adenosine triphosphate) began to make their appearance. It seems that with lymphadenitis, a qualitative change of the phosphatase activity takes place. A special characteristic pattern of phosphatase activity has been described in both 'early' and 'caseating' tuberculous lymphadenitis. In malignant lymphomas it was noticed that no activity was encountered with any of the four substrates in reticulum cell sarcoma. However, in lymphosarcoma a positive activity was obtained when either beta-glycerophosphate or adenosine triphosphate substrates was used, to the extent that one can depend upon this characteristic phosphatase activity in differentiating between reticulum cell sarcoma and lymphosarcoma. However, no enzymatic activity was obtained when the other two phosphate esters were used.", "contents": "Histochemistry of normal and diseased human lymph nodes. Gomori's metal precipitate technique was used to demonstrate the phosphatase activity of the human cervical lymph node in health and disease, using four different phosphate esters (sodium beta-glycerophosphate and adenosine triphosphate at pH 9, riboflavin 5'-phosphate at pH 9.2 and 5'-monophosphoric acid at pH 8.3). In fetal lymph nodes, using 5'-monophosphoric acid, an outstanding positive activity was noticed in the lymphatic follicles. With the other three substrates there was either no nodular reaction or just a narrow rim of positive activity around the follicles, the internodular tissue being negative with all four substrates used. With chronic non-specific lymphadenitis the enzyme hydrolysing the three substrates (beta-glycerophosphate, riboflavin 5'-phosphate and adenosine triphosphate) began to make their appearance. It seems that with lymphadenitis, a qualitative change of the phosphatase activity takes place. A special characteristic pattern of phosphatase activity has been described in both 'early' and 'caseating' tuberculous lymphadenitis. In malignant lymphomas it was noticed that no activity was encountered with any of the four substrates in reticulum cell sarcoma. However, in lymphosarcoma a positive activity was obtained when either beta-glycerophosphate or adenosine triphosphate substrates was used, to the extent that one can depend upon this characteristic phosphatase activity in differentiating between reticulum cell sarcoma and lymphosarcoma. However, no enzymatic activity was obtained when the other two phosphate esters were used."} {"id": "PMID:183450", "title": "[Influence of immobilization on spermatogenesis].", "content": "The author investigated the influence of immobilization stress on spermiogenesis in rats. After 96 h immobilization, histological changes began to manifest in the form of a practically complete disappearance of the cell population of the wall of seminiferous tubule as well as a markedly increased number of cells with pathologic mitoses. Enzymological investigations have shown in particular groups (24, 48 and 96 h immobilization) various changes of activity (of acid and alkaline phosphatase, nonspecific esterase and glucose-6-phosphatase) which, after temporary negativity, became positive again in the last group.", "contents": "[Influence of immobilization on spermatogenesis]. The author investigated the influence of immobilization stress on spermiogenesis in rats. After 96 h immobilization, histological changes began to manifest in the form of a practically complete disappearance of the cell population of the wall of seminiferous tubule as well as a markedly increased number of cells with pathologic mitoses. Enzymological investigations have shown in particular groups (24, 48 and 96 h immobilization) various changes of activity (of acid and alkaline phosphatase, nonspecific esterase and glucose-6-phosphatase) which, after temporary negativity, became positive again in the last group."} {"id": "PMID:183452", "title": "Electromyographic changes in automechanics with increased heavy metal levels.", "content": "Twenty automechanics possessing increased whole blood values of one or more of the following heavy metals; chromium, copper, lead, manganese and nickel, were studied for peripheral nerve affection by means of electromyography (both sensoric and motoric nerve potentials were recorded). The heavy metal contents were related to the findings of denervation, distal motor latency, distal sensory latency, motoric and sensoric conduction velocities. Apart from two workers, in whom only lead was assayed, the remaining group of 18 were assayed for all heavy metals under study. Six workers showed increased distal motor and/or sensory latency and seven decreased nerve conduction velocity (four motoric and three sensoric affections). Of the workers with nerve affection, three showed increased levels of lead (nickel and chromium also raised). Four workers showed increased lead, nickel and chromium and one of lead, chromium and manganese. All in all, 10 out of 20 workers (50 percent) with elevated lead levels showed definite signs of peripheral neuropathy and seven out of 14 with raised nickel values showed these signs but they could all be accounted for by the increased lead levels. All except seven workers with raised lead levels in the whole group showed values above the critical limit of 80.0 mug/100 ml in whole blood. The data argue for the highly toxic effect of lead and other heavy metals on the peripheral nervous system and stress the diverse toxic exposure which automechanics undergo during their work. The possibility of there being a synergistic action between heavy metals and components of mineral oil and petroleum is discussed.", "contents": "Electromyographic changes in automechanics with increased heavy metal levels. Twenty automechanics possessing increased whole blood values of one or more of the following heavy metals; chromium, copper, lead, manganese and nickel, were studied for peripheral nerve affection by means of electromyography (both sensoric and motoric nerve potentials were recorded). The heavy metal contents were related to the findings of denervation, distal motor latency, distal sensory latency, motoric and sensoric conduction velocities. Apart from two workers, in whom only lead was assayed, the remaining group of 18 were assayed for all heavy metals under study. Six workers showed increased distal motor and/or sensory latency and seven decreased nerve conduction velocity (four motoric and three sensoric affections). Of the workers with nerve affection, three showed increased levels of lead (nickel and chromium also raised). Four workers showed increased lead, nickel and chromium and one of lead, chromium and manganese. All in all, 10 out of 20 workers (50 percent) with elevated lead levels showed definite signs of peripheral neuropathy and seven out of 14 with raised nickel values showed these signs but they could all be accounted for by the increased lead levels. All except seven workers with raised lead levels in the whole group showed values above the critical limit of 80.0 mug/100 ml in whole blood. The data argue for the highly toxic effect of lead and other heavy metals on the peripheral nervous system and stress the diverse toxic exposure which automechanics undergo during their work. The possibility of there being a synergistic action between heavy metals and components of mineral oil and petroleum is discussed."} {"id": "PMID:183453", "title": "Anterior horn cell changes in a case of neurolathyrism.", "content": "Light and electron microscopic studies were made of the anterior horn cells in a case of neurolathyrism. Eosinophilic inclusions were observed at the light microscopic level. Fine structural study revealed the presence of two types of cytoplasmic inclusions. The first were aggregates of filaments, approximately 80-100 A in width, arranged in small bundles. The second were crystalloid structures composed of elongated elements, about 800 A wide, with hexagonal cross sections. The relationship to each other and the significance of these inclusions are unknown.", "contents": "Anterior horn cell changes in a case of neurolathyrism. Light and electron microscopic studies were made of the anterior horn cells in a case of neurolathyrism. Eosinophilic inclusions were observed at the light microscopic level. Fine structural study revealed the presence of two types of cytoplasmic inclusions. The first were aggregates of filaments, approximately 80-100 A in width, arranged in small bundles. The second were crystalloid structures composed of elongated elements, about 800 A wide, with hexagonal cross sections. The relationship to each other and the significance of these inclusions are unknown."} {"id": "PMID:183454", "title": "Ultrastructural study of so-called curvilinear bodies and fingerprint structures in lymphocytes in late-infantile amaurotic idiocy.", "content": "Peripheral lymphocytes of 6 patients with late-infantile amaurotic idiocy were examined with the electron microscope for the occurrence of curvilinear bodies and fingerprint structures. In 3 of the patients predominantly curvilinear bodies were found; in 1 case they contained some fingerprint profiles. In the remaining 3 patients curvilinear bodies were relatively scarce, whereas fingerprint structures prevailed. Moreover, pleomorphic bodies with rectilinear profiles and parallel tubular inclusion bodies were present. No lymphocytes with vacuoles were observed in any of the patients. The sural nerve biopsies of all patients revealed curvilinear bodies. This tissue consequently may be considered to give more reliable information in comparison with the lymphocyte. The likelihood of transition of one type inclusion body into another, the specificity of the curvilinear body and, to our mind, the rigid classification of the amaurotic idiocy into a curvilinear and a fingerprint type, are discussed.", "contents": "Ultrastructural study of so-called curvilinear bodies and fingerprint structures in lymphocytes in late-infantile amaurotic idiocy. Peripheral lymphocytes of 6 patients with late-infantile amaurotic idiocy were examined with the electron microscope for the occurrence of curvilinear bodies and fingerprint structures. In 3 of the patients predominantly curvilinear bodies were found; in 1 case they contained some fingerprint profiles. In the remaining 3 patients curvilinear bodies were relatively scarce, whereas fingerprint structures prevailed. Moreover, pleomorphic bodies with rectilinear profiles and parallel tubular inclusion bodies were present. No lymphocytes with vacuoles were observed in any of the patients. The sural nerve biopsies of all patients revealed curvilinear bodies. This tissue consequently may be considered to give more reliable information in comparison with the lymphocyte. The likelihood of transition of one type inclusion body into another, the specificity of the curvilinear body and, to our mind, the rigid classification of the amaurotic idiocy into a curvilinear and a fingerprint type, are discussed."} {"id": "PMID:183451", "title": "[Infantile generalized ceroid-Lipofuscinosis (type Hagberg-Santavuori). A new case and a retrospective study of two observations (author's transl)].", "content": "Three post mortem studies of cases of infantile generalized ceroid-lipofuscinosis are reported: two of them were published under other classifications but our retrospective study warrants their inclusion in the infantile group of ceroid-lipofuscinosis. The children died at the respective ages of 4, 5 8/12 and 8 years and this allows interesting morphological comparisons: 1 degree there is an increasingly severe loss of cortical neurons, of Purkinje cells and of neurons in the griseum pontis with age. Intracytoplasmic inclusions mainly of a granular osmiophilic nature were found in all other neurons and glial cells; 2 degrees the involvement of the visceral organs is especially striking and permits an easier diagnosis under light microscopy, unlike the late infantile and juvenile forms of ceroid-lipofuscinosis. Electron microscopy supports the observation by Anzil et al. (1975) concerning the relative pleiomorphism of the inclusions; 3 degree the diffuse accumulation of inclusions in the skin and its appendages ensures a rapid diagnosis by skin biopsy.", "contents": "[Infantile generalized ceroid-Lipofuscinosis (type Hagberg-Santavuori). A new case and a retrospective study of two observations (author's transl)]. Three post mortem studies of cases of infantile generalized ceroid-lipofuscinosis are reported: two of them were published under other classifications but our retrospective study warrants their inclusion in the infantile group of ceroid-lipofuscinosis. The children died at the respective ages of 4, 5 8/12 and 8 years and this allows interesting morphological comparisons: 1 degree there is an increasingly severe loss of cortical neurons, of Purkinje cells and of neurons in the griseum pontis with age. Intracytoplasmic inclusions mainly of a granular osmiophilic nature were found in all other neurons and glial cells; 2 degrees the involvement of the visceral organs is especially striking and permits an easier diagnosis under light microscopy, unlike the late infantile and juvenile forms of ceroid-lipofuscinosis. Electron microscopy supports the observation by Anzil et al. (1975) concerning the relative pleiomorphism of the inclusions; 3 degree the diffuse accumulation of inclusions in the skin and its appendages ensures a rapid diagnosis by skin biopsy."} {"id": "PMID:183456", "title": "V. a new method for the assessment of skeletal maturity- the mat- method (mean appearance time of bone stages).", "content": "By means of probit analysis of the age at the appearance of the various bone stages according to Tanner-Whitehouse and using a logarithmic time concept (logarithmic conceptional age), a new approach to the evaluation of skeletal maturity has been elaborated. The maturity score of each bone stage corresponds to th4 mean maturity level of the observation of being within each stage. The individual maturity level is calculated by averaging the maturity scores of the stages of the various bones and is then evaluated is standard deviation scores by comparing with teh Gaussian fitted distribution of averages maturity scores of the age of the child examined. Special conditions apply for the scoring of a first and a last bone stage in a sequence, which will introduce less bias in the estimation of individual skeletal maturity with the MAT-method than with the TW-method. Ossification during early infancy can be evaluated and sequence polymorphism be detected by using the bone stage chart of the MAT-method.", "contents": "V. a new method for the assessment of skeletal maturity- the mat- method (mean appearance time of bone stages). By means of probit analysis of the age at the appearance of the various bone stages according to Tanner-Whitehouse and using a logarithmic time concept (logarithmic conceptional age), a new approach to the evaluation of skeletal maturity has been elaborated. The maturity score of each bone stage corresponds to th4 mean maturity level of the observation of being within each stage. The individual maturity level is calculated by averaging the maturity scores of the stages of the various bones and is then evaluated is standard deviation scores by comparing with teh Gaussian fitted distribution of averages maturity scores of the age of the child examined. Special conditions apply for the scoring of a first and a last bone stage in a sequence, which will introduce less bias in the estimation of individual skeletal maturity with the MAT-method than with the TW-method. Ossification during early infancy can be evaluated and sequence polymorphism be detected by using the bone stage chart of the MAT-method."} {"id": "PMID:183457", "title": "IV. skeletal development from birth to 7 years.", "content": "The skeletal development of 212 randomly selected Swedish urban children has been investigated as part of a prospective longitudinal study of growth and development. Radiograms of the hand and wrist were taken at specified ages. Up to the age of seven years 2.191 radiograms were assessed. When comparing the timing of the first ossification of the various bones in the present study and an older Swedish investigation a secular trend was found. In contrast to a North-American growth study, there was a striking similarity of the pattern of the first ossification in the two Swedish investigations for both sexes separately. However, the relative sex differences of the ossification were quite similar in the North-American growth study and the present investigation. In comparison with British children the skeletal development of Swedish children was advanced at all ages, the advancement being greater for epiphyseal bones than for carpal bones.", "contents": "IV. skeletal development from birth to 7 years. The skeletal development of 212 randomly selected Swedish urban children has been investigated as part of a prospective longitudinal study of growth and development. Radiograms of the hand and wrist were taken at specified ages. Up to the age of seven years 2.191 radiograms were assessed. When comparing the timing of the first ossification of the various bones in the present study and an older Swedish investigation a secular trend was found. In contrast to a North-American growth study, there was a striking similarity of the pattern of the first ossification in the two Swedish investigations for both sexes separately. However, the relative sex differences of the ossification were quite similar in the North-American growth study and the present investigation. In comparison with British children the skeletal development of Swedish children was advanced at all ages, the advancement being greater for epiphyseal bones than for carpal bones."} {"id": "PMID:183458", "title": "Tumor growth of the reticuloendothelial system.", "content": "From the author's hitherto studies on the reticuloendothelial system (RES) it was concluded that the RES is not a single cell system of identical origin, morphology and function but is a group of several types of cells of different origin. From this point of view the heterogeneity of tumors of the RES was studied to reveal the following results. Tumors of the \"Reticuloendothel\" (Aschoff) reveal pictures of endothelioma, while tumors of histiocytes in connective tissue show findings of fibrohistiocytoma. Histiocytes and reticulum cells of lymph nodes are respectively independent cells, and reticulum cells do not partake in the in the development of histiocytosis or histiocytic sarcoma. Follicular lymphoma is a neoplastic growth of reticulum cells having desmosomes in lymph follicles, and tumor cells of the majority of reticulum cell sarcoma are similar to the cells forming the lymph node anlage in the early fetal stage (lymphoreticular cell). Ewing's sarcoma is considered to be a kind of angiopericytoma.", "contents": "Tumor growth of the reticuloendothelial system. From the author's hitherto studies on the reticuloendothelial system (RES) it was concluded that the RES is not a single cell system of identical origin, morphology and function but is a group of several types of cells of different origin. From this point of view the heterogeneity of tumors of the RES was studied to reveal the following results. Tumors of the \"Reticuloendothel\" (Aschoff) reveal pictures of endothelioma, while tumors of histiocytes in connective tissue show findings of fibrohistiocytoma. Histiocytes and reticulum cells of lymph nodes are respectively independent cells, and reticulum cells do not partake in the in the development of histiocytosis or histiocytic sarcoma. Follicular lymphoma is a neoplastic growth of reticulum cells having desmosomes in lymph follicles, and tumor cells of the majority of reticulum cell sarcoma are similar to the cells forming the lymph node anlage in the early fetal stage (lymphoreticular cell). Ewing's sarcoma is considered to be a kind of angiopericytoma."} {"id": "PMID:183459", "title": "Malignant fibrous histiocytoma of bone.", "content": "Existence of an entity called malignant fibrous histiocytoma of bone was emphasized, based on two of our own cases experienced recently and on previous reports related to this tumor. Histologically the tumor resembles markedly the malignant fibrous histiocytoma originating in the soft part. In addition, an attempt was made to clarify its biological behavior, histological subclassification and criteria to be malignant and differential diagnoses from several other bone diseases which sometimes mimic this malignant bone tumor.", "contents": "Malignant fibrous histiocytoma of bone. Existence of an entity called malignant fibrous histiocytoma of bone was emphasized, based on two of our own cases experienced recently and on previous reports related to this tumor. Histologically the tumor resembles markedly the malignant fibrous histiocytoma originating in the soft part. In addition, an attempt was made to clarify its biological behavior, histological subclassification and criteria to be malignant and differential diagnoses from several other bone diseases which sometimes mimic this malignant bone tumor."} {"id": "PMID:183460", "title": "The inability of a diabetogenic virus to induce diabetes mellitus in athymic (nude) mice.", "content": "The effect of a known diabetogenic M-strain encephalomyocarditis (EMC)-virus in athymic nude mice (lacking the thymus-dependent lymphocyte system), and in heteroxygous littermates and homozygous normal mice of the background strain (C57/B16) was investigated. While by 3 weeks 4 out of 4 surviving virus-inoculated littermates and 9 out of 9 inoculated normal mice developed diabetes mellitus, none of the 7 surviving virus-inoculated nude mice became diabetic. Virus was isolated from all inoculated animals, including non-diabetic nude mice. It is concluded that it is the response of the thymus-dependent lymphocyte system evoked by the virus rather than the virus itself that leads to damage to the insulin producing cell.", "contents": "The inability of a diabetogenic virus to induce diabetes mellitus in athymic (nude) mice. The effect of a known diabetogenic M-strain encephalomyocarditis (EMC)-virus in athymic nude mice (lacking the thymus-dependent lymphocyte system), and in heteroxygous littermates and homozygous normal mice of the background strain (C57/B16) was investigated. While by 3 weeks 4 out of 4 surviving virus-inoculated littermates and 9 out of 9 inoculated normal mice developed diabetes mellitus, none of the 7 surviving virus-inoculated nude mice became diabetic. Virus was isolated from all inoculated animals, including non-diabetic nude mice. It is concluded that it is the response of the thymus-dependent lymphocyte system evoked by the virus rather than the virus itself that leads to damage to the insulin producing cell."} {"id": "PMID:183462", "title": "Clofibrate in type II hyperlipoproteinemia.", "content": "As a part of a double-blind randomized study, the safety and the lipid- and uric acid-lowering effect of clofibrate have been evaluated in 28 patients with type II hyperlipoproteinemia (HLP). A highly significant reduction of serum cholesterol occurred in type IIa and of serum triglyceride and choelsterol in type IIb HLP throughout the 60-week observation period (p less than 0.01). Of the patients with types IIa and IIb HLP, 65% had at least a 25% reduction of serum cholesterol. Uric acid was significantly reduced only during the first period of treatment (p less than 0.05). In the laboratory measurements concerning safety, a persistent, slight reduction was observed in Hb, hematocrit and alkaline phosphatase. No significant clinical side-effects were noted. Clofibrate is considered effective as a lipid-lowering agent in many cases of type II HLP.", "contents": "Clofibrate in type II hyperlipoproteinemia. As a part of a double-blind randomized study, the safety and the lipid- and uric acid-lowering effect of clofibrate have been evaluated in 28 patients with type II hyperlipoproteinemia (HLP). A highly significant reduction of serum cholesterol occurred in type IIa and of serum triglyceride and choelsterol in type IIb HLP throughout the 60-week observation period (p less than 0.01). Of the patients with types IIa and IIb HLP, 65% had at least a 25% reduction of serum cholesterol. Uric acid was significantly reduced only during the first period of treatment (p less than 0.05). In the laboratory measurements concerning safety, a persistent, slight reduction was observed in Hb, hematocrit and alkaline phosphatase. No significant clinical side-effects were noted. Clofibrate is considered effective as a lipid-lowering agent in many cases of type II HLP."} {"id": "PMID:183463", "title": "Selective removal of hypersecreting pituitary adenomas? An analysis of endocrine function, operative and microscopical findings in 101 cases.", "content": "The aim of this study of 101 pre- and postoperatively controlled hypersecreting pituitary adenomas (80 acromegalies, 15 Cushing's diseases, 6 Nelson's syndromes) was to establish in what cases a selective adenoma extirpation by the transnasal route is possible and advisable. In primary operations on acromegalics with small and medium size tumours 92% were postoperatively GH normal. Eighty five per cent of these had intact pituitary function. The results with larger tumours were worse (72%). During a control period of 1.5-5.5 years a renewed elevation of GH levels was observed in three cases, all in the first year, but never after clearly selective adenomectomy. These results, and the anterior lobe biopsies, which showed no GH cell hyperplasia, favour selective adenoma extirpation. In contrast to acromegaly, nodular ACTH cell hyperplasia in the anterior lobe was found in most cases of Cushing's disease, and therefore complete hypophysectomy was performed. The cortisol levels became either normal or, in most cases, lower than normal. A selective operation was performed on 6 Nelson tumors. The ACTH values became normal in about 50% of the patients but there was a tendency towards recurrence. Our experiences with Cushing's disease and Nelson's syndrome lead us to recommend total hypophysectomy.", "contents": "Selective removal of hypersecreting pituitary adenomas? An analysis of endocrine function, operative and microscopical findings in 101 cases. The aim of this study of 101 pre- and postoperatively controlled hypersecreting pituitary adenomas (80 acromegalies, 15 Cushing's diseases, 6 Nelson's syndromes) was to establish in what cases a selective adenoma extirpation by the transnasal route is possible and advisable. In primary operations on acromegalics with small and medium size tumours 92% were postoperatively GH normal. Eighty five per cent of these had intact pituitary function. The results with larger tumours were worse (72%). During a control period of 1.5-5.5 years a renewed elevation of GH levels was observed in three cases, all in the first year, but never after clearly selective adenomectomy. These results, and the anterior lobe biopsies, which showed no GH cell hyperplasia, favour selective adenoma extirpation. In contrast to acromegaly, nodular ACTH cell hyperplasia in the anterior lobe was found in most cases of Cushing's disease, and therefore complete hypophysectomy was performed. The cortisol levels became either normal or, in most cases, lower than normal. A selective operation was performed on 6 Nelson tumors. The ACTH values became normal in about 50% of the patients but there was a tendency towards recurrence. Our experiences with Cushing's disease and Nelson's syndrome lead us to recommend total hypophysectomy."} {"id": "PMID:183474", "title": "On the prosthetic groups of L-tryptophan 2,3-dioxygenase from Pseudomonas: evidence for noninvolvement of copper in the reaction.", "content": "The amounts of copper present in highly purified preparations of L-tryptophan 2,3-dioxygenase from Pseudomonas fluorescens have been shown to be negligible by six different methods of copper determination. It has also been demonstrated that, during the purification, the heme content of enzyme preparations increased in parallel with the specific enzyme activity, whereas that of copper decreased. These results, together with the finding that the inhibitory effects of copper chelators on the enzyme could be attributable to some other action of these chemicals rather than to their chelating properties, indicate that copper is not an essential component of L-tryptophan 2,3-dioxygenase.", "contents": "On the prosthetic groups of L-tryptophan 2,3-dioxygenase from Pseudomonas: evidence for noninvolvement of copper in the reaction. The amounts of copper present in highly purified preparations of L-tryptophan 2,3-dioxygenase from Pseudomonas fluorescens have been shown to be negligible by six different methods of copper determination. It has also been demonstrated that, during the purification, the heme content of enzyme preparations increased in parallel with the specific enzyme activity, whereas that of copper decreased. These results, together with the finding that the inhibitory effects of copper chelators on the enzyme could be attributable to some other action of these chemicals rather than to their chelating properties, indicate that copper is not an essential component of L-tryptophan 2,3-dioxygenase."} {"id": "PMID:183478", "title": "Binuclear copper clusters as active sites for oxidases.", "content": "Binuclear cupric ion clusters have been established in: human ceruloplasmin, hemocyanin, and mushroom tyrosinase. Substantial evidence makes it very probable that fungal laccase and zucchini ascorbate oxidase contain this cluster. Some evidence makes it possible that copper clusters function in the catalytic cycles of cytochrome oxidase (mammalian) and dopamine-beta-hydroxylase. These studies throw light on the criteria which must be employed to establish the existence of functional binuclear copper clusters in enzymes: (1) Stoichiometric Criteria: binding of O2 and CO with Cu/ligand = 2; redox titrations with n = 2; (2) Physical and Chemical Criteria: magnetic evidence of diminished paramagnetism of cupric centers, EPR evidence of broadened or absent absorptions, EPR evidence of magnetic dipolar interactions among cupric ions; absorption bands characteristic of Cu(II)-Cu(II) complexes; laser resonance raman scattering characteristic of peroxidic dioxygen in the oxyforms.", "contents": "Binuclear copper clusters as active sites for oxidases. Binuclear cupric ion clusters have been established in: human ceruloplasmin, hemocyanin, and mushroom tyrosinase. Substantial evidence makes it very probable that fungal laccase and zucchini ascorbate oxidase contain this cluster. Some evidence makes it possible that copper clusters function in the catalytic cycles of cytochrome oxidase (mammalian) and dopamine-beta-hydroxylase. These studies throw light on the criteria which must be employed to establish the existence of functional binuclear copper clusters in enzymes: (1) Stoichiometric Criteria: binding of O2 and CO with Cu/ligand = 2; redox titrations with n = 2; (2) Physical and Chemical Criteria: magnetic evidence of diminished paramagnetism of cupric centers, EPR evidence of broadened or absent absorptions, EPR evidence of magnetic dipolar interactions among cupric ions; absorption bands characteristic of Cu(II)-Cu(II) complexes; laser resonance raman scattering characteristic of peroxidic dioxygen in the oxyforms."} {"id": "PMID:183481", "title": "The biological role of ceruloplasmin and its oxidase activity.", "content": "Ceruloplasmin (ferroxidase) the blue Cu-protein of vertebrate plasma, possesses significant oxidase activity towards Fe(II) and numerous aromatic amines and phenols. Its ferroxidase activity has led to the discovery that it is a molecular link between copper and iron metabolism. Ceruloplasmin mobilizes iron into the plasma from iron storage cells in the liver. An additional role of Cp may be as a contributor to the regulation of the balance of biogenic amines through its oxidase action on the epinephrine and the hydroxyindole series. Ceruloplasmin also serves as a major copper transport vehicle, comparable to transferrin for iron. Evidence is presented that the copper atoms of Cp are a prerequisite for copper utilization in the biosynthesis of cytochrome oxidase. The ability of Cp to release copper at specific cellular sites is believed to be related to its broad substrate spectrum of biological reducing agents. Thus Cp is a serum protein with several important functions, all of which are directly related to its oxidase activity.", "contents": "The biological role of ceruloplasmin and its oxidase activity. Ceruloplasmin (ferroxidase) the blue Cu-protein of vertebrate plasma, possesses significant oxidase activity towards Fe(II) and numerous aromatic amines and phenols. Its ferroxidase activity has led to the discovery that it is a molecular link between copper and iron metabolism. Ceruloplasmin mobilizes iron into the plasma from iron storage cells in the liver. An additional role of Cp may be as a contributor to the regulation of the balance of biogenic amines through its oxidase action on the epinephrine and the hydroxyindole series. Ceruloplasmin also serves as a major copper transport vehicle, comparable to transferrin for iron. Evidence is presented that the copper atoms of Cp are a prerequisite for copper utilization in the biosynthesis of cytochrome oxidase. The ability of Cp to release copper at specific cellular sites is believed to be related to its broad substrate spectrum of biological reducing agents. Thus Cp is a serum protein with several important functions, all of which are directly related to its oxidase activity."} {"id": "PMID:183483", "title": "The iron-sulfur centers and the function of hydrogenase from Clostridium pasteurianum.", "content": "Hydrogenase from C. pasteurianum is an iron-sulfur protein containing at least two tetrameric iron-sulfur centers. Information on the structure of the remaining iron atoms must await future investigation. Although the EPR spectra of dithionite-reduced hydrogenase and eight-iron Fd showed some similarity, the CD spectra clearly indicated a difference. The tetrameric iron-sulfur centers of hydrogenase were shown to undergo redox changes when hydrogenase was oxidized or reduced. However, no evidence is now available to support a role for the tetrameric Fe-S centers, responsible for the EPR spectrum A, as the primary site for H2 binding and activation. Because we have found that the [Fe4S4(SR)4]-containing ferredoxins do not have hydrogenase activity, it is conceivable that the additional iron atoms and/or certain amino acid residues of hydrogenase also contribute to the unique catalytic properties of this enzyme. Chemical synthesis of Fe-S clusters with different peptide environments and with hydrogenase function would lead to the identification of these functional groups. X-ray diffraction studies on hydrogenase will certainly complement the other approaches. Knowledge of the structure of the active site of hydrogenase will certainly accelerate research into: (1) the synthesis of a stable catalyst to replace hydrogenase in systems designed to produce H2 by coupling this catalyst to a photoreducing system; and (2) the elucidation of the active sites of more complicated iron-sulfur enzymes such as nitrogenase.", "contents": "The iron-sulfur centers and the function of hydrogenase from Clostridium pasteurianum. Hydrogenase from C. pasteurianum is an iron-sulfur protein containing at least two tetrameric iron-sulfur centers. Information on the structure of the remaining iron atoms must await future investigation. Although the EPR spectra of dithionite-reduced hydrogenase and eight-iron Fd showed some similarity, the CD spectra clearly indicated a difference. The tetrameric iron-sulfur centers of hydrogenase were shown to undergo redox changes when hydrogenase was oxidized or reduced. However, no evidence is now available to support a role for the tetrameric Fe-S centers, responsible for the EPR spectrum A, as the primary site for H2 binding and activation. Because we have found that the [Fe4S4(SR)4]-containing ferredoxins do not have hydrogenase activity, it is conceivable that the additional iron atoms and/or certain amino acid residues of hydrogenase also contribute to the unique catalytic properties of this enzyme. Chemical synthesis of Fe-S clusters with different peptide environments and with hydrogenase function would lead to the identification of these functional groups. X-ray diffraction studies on hydrogenase will certainly complement the other approaches. Knowledge of the structure of the active site of hydrogenase will certainly accelerate research into: (1) the synthesis of a stable catalyst to replace hydrogenase in systems designed to produce H2 by coupling this catalyst to a photoreducing system; and (2) the elucidation of the active sites of more complicated iron-sulfur enzymes such as nitrogenase."} {"id": "PMID:183484", "title": "Studies on histamine-retaining granules obtained from isolated rat mast cells.", "content": "Histamine-retaining granules were isolated from rat mast cells after sonication in either sucrose of Ficoll-Hypaque media. The preparations obtained were compared in regard to recovery and spontaneous loss of histamine. The effect of agents known to release histamine from intact rat mast cells (antigen, compound 48/80, decylamine, the ionophores A23187 and X537A as well as ATP) was studied on the granules. Antigen and compound 48/80 did not release histamine. Decylamine and X537A induced a pronounced release independent of the presence of divalent cations. ATP caused a small, but significant release, which showed an absolute requirement for magnesium. A23187 released histamine only in the presence of either calcium or magnesium, and this release was unaffected by certain agents known to inhibit histamine release from intact rat mast cells. The results seem to exclude the possibility that agents known to induce release of histamine from intact rat mast cells by a calcium-and energy-dependent process would exert this action through a direct effect on intracellularly localized granules.", "contents": "Studies on histamine-retaining granules obtained from isolated rat mast cells. Histamine-retaining granules were isolated from rat mast cells after sonication in either sucrose of Ficoll-Hypaque media. The preparations obtained were compared in regard to recovery and spontaneous loss of histamine. The effect of agents known to release histamine from intact rat mast cells (antigen, compound 48/80, decylamine, the ionophores A23187 and X537A as well as ATP) was studied on the granules. Antigen and compound 48/80 did not release histamine. Decylamine and X537A induced a pronounced release independent of the presence of divalent cations. ATP caused a small, but significant release, which showed an absolute requirement for magnesium. A23187 released histamine only in the presence of either calcium or magnesium, and this release was unaffected by certain agents known to inhibit histamine release from intact rat mast cells. The results seem to exclude the possibility that agents known to induce release of histamine from intact rat mast cells by a calcium-and energy-dependent process would exert this action through a direct effect on intracellularly localized granules."} {"id": "PMID:183485", "title": "Pyophosphate-induced inflammation: an in vivo study of the interrelationship of intracellular cyclic AMP and cyclic GMP.", "content": "The changes in leucocyte concentrations of cyclic AMP and cyclic GMP were monitored during pyrophosphate-induced pleurisy in rats. A classical 'Yin Yang' relationship was demonstrated.", "contents": "Pyophosphate-induced inflammation: an in vivo study of the interrelationship of intracellular cyclic AMP and cyclic GMP. The changes in leucocyte concentrations of cyclic AMP and cyclic GMP were monitored during pyrophosphate-induced pleurisy in rats. A classical 'Yin Yang' relationship was demonstrated."} {"id": "PMID:183491", "title": "The neurologic complications of alcoholism.", "content": "Neurologic complications may appear before the primary disease, alcoholism, is recognized. The common syndromes are polyneuropathy, the withdrawal syndrome and the combination of Wernicke's encephalopathy and Korsakoff's psychosis. Other conspicuous clinical pictures include ataxia of cerebellar origin, convulsions, acute hallucinosis, myopathy and coma. Rarer disorders are Marchiafava-Bignami disease and central pontine myelinolysis.", "contents": "The neurologic complications of alcoholism. Neurologic complications may appear before the primary disease, alcoholism, is recognized. The common syndromes are polyneuropathy, the withdrawal syndrome and the combination of Wernicke's encephalopathy and Korsakoff's psychosis. Other conspicuous clinical pictures include ataxia of cerebellar origin, convulsions, acute hallucinosis, myopathy and coma. Rarer disorders are Marchiafava-Bignami disease and central pontine myelinolysis."} {"id": "PMID:183492", "title": "Effects of ethanol on bile acid and cholesterol metabolism.", "content": "The effects of ethanol on plasma lipid and lipoprotein concentrations and on the fecal excretion of neutral sterols and bile acids were studied in three patients with ethanol-induced hyperlipidemia and in four normolipidemic men. In the three patients, plasma triglyceride and cholesterol concentrations were much higher with ethanol than during periods when ethanol was isocalorically substituted with either carbohydrate or both fat and carbohydrate. In the normolipidemic subjects, plasma lipids especially in very low density lipoproteins, were higher with ethanol consumption only in comparison with a balanced diet but not when compared with carbohydrate-rich diets. Triglyceride enrichment of low density lipoproteins occurred uniformly with ethanol. Total sterol excretion, measured by isotope dilution and chemical assay, was similar during ethanol and control periods in two out of the three hyperlipidemic subjects. However, the proportion of bile acids was increased in all three hyperlipidemic subjects but in only one normolipidemic subject while on ethanol. Since cholesterol turnover did not appear to be necessarily influenced by ethanol, as judged either by total endogenous sterol excretion or from the slope of the plasma cholesterol specific radioactivity-time curve, the ethanol-induced increase in bile acid excretion amy not be analogous to other clinical disorders in which increased bile acid excretion and hypertriglyceridemia are associated with raised sterol production.", "contents": "Effects of ethanol on bile acid and cholesterol metabolism. The effects of ethanol on plasma lipid and lipoprotein concentrations and on the fecal excretion of neutral sterols and bile acids were studied in three patients with ethanol-induced hyperlipidemia and in four normolipidemic men. In the three patients, plasma triglyceride and cholesterol concentrations were much higher with ethanol than during periods when ethanol was isocalorically substituted with either carbohydrate or both fat and carbohydrate. In the normolipidemic subjects, plasma lipids especially in very low density lipoproteins, were higher with ethanol consumption only in comparison with a balanced diet but not when compared with carbohydrate-rich diets. Triglyceride enrichment of low density lipoproteins occurred uniformly with ethanol. Total sterol excretion, measured by isotope dilution and chemical assay, was similar during ethanol and control periods in two out of the three hyperlipidemic subjects. However, the proportion of bile acids was increased in all three hyperlipidemic subjects but in only one normolipidemic subject while on ethanol. Since cholesterol turnover did not appear to be necessarily influenced by ethanol, as judged either by total endogenous sterol excretion or from the slope of the plasma cholesterol specific radioactivity-time curve, the ethanol-induced increase in bile acid excretion amy not be analogous to other clinical disorders in which increased bile acid excretion and hypertriglyceridemia are associated with raised sterol production."} {"id": "PMID:183493", "title": "Mechanism and site of small intestinal uptake of vitamin D3 in pharmacological concentrations.", "content": "The site and mechanism of initial uptake of 1,2-3H vitamin D3 pharmacological concentrations was investigated using everted rat small bowel sacs incubated in a micellar medium. The mean +/- SE uptake rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 6.7 +/- 0.26, 7.8 +/- 0.54, and 3.3 +/- 0.20 nmole/min/100 mg tissue, respectively. Incubation with the addition of 10(-3) M 2,4-dinitrophenol, or 10(-3) M KCN, or under nitrogen atmosphere did not change (P greater than 0.05) the above rates of absorption. Incremental increases in the concentration of vitamin D in the incubation medium up to 1200 muM resulted in a linear increase in the uptake rate indicating lack of saturation kinetics. In all the above experiments, greater rate of uptake of the vitamin occurred in the proximal and medial small bowel than the distal small bowel (P less than 0.01). The above experiments indicate that vitamin D3 in this range of concentrations is taken up by enterocytes by a nonsaturable passive diffusion mechanism showing no evidence for carrier mediation. The rate of intestinal uptake is highest in the proximal and medial segments of the small bowel.", "contents": "Mechanism and site of small intestinal uptake of vitamin D3 in pharmacological concentrations. The site and mechanism of initial uptake of 1,2-3H vitamin D3 pharmacological concentrations was investigated using everted rat small bowel sacs incubated in a micellar medium. The mean +/- SE uptake rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 6.7 +/- 0.26, 7.8 +/- 0.54, and 3.3 +/- 0.20 nmole/min/100 mg tissue, respectively. Incubation with the addition of 10(-3) M 2,4-dinitrophenol, or 10(-3) M KCN, or under nitrogen atmosphere did not change (P greater than 0.05) the above rates of absorption. Incremental increases in the concentration of vitamin D in the incubation medium up to 1200 muM resulted in a linear increase in the uptake rate indicating lack of saturation kinetics. In all the above experiments, greater rate of uptake of the vitamin occurred in the proximal and medial small bowel than the distal small bowel (P less than 0.01). The above experiments indicate that vitamin D3 in this range of concentrations is taken up by enterocytes by a nonsaturable passive diffusion mechanism showing no evidence for carrier mediation. The rate of intestinal uptake is highest in the proximal and medial segments of the small bowel."} {"id": "PMID:183494", "title": "Improvement in jejunal enzyme adaptation in obese adult-onset diabetic patients following a 30-day fast.", "content": "The adaptive responses of gastrointestinal enzymes, glucose tolerance, and plasma insulin to diet, folic acid, and insulin of five obese adult-onset diabetic patients were studied before and after a 30-day fast. Their data were compared to the adaptive responses of gastrointestinal enzymes to diet, folic acid, and insulin of 15 normal male volunteer subjects, ages 18 to 24. Each group during each testing period received a carbohydrate diet (50% calories as carbohydrate consisting of 1/2 glucose and 1/2 fructose) and a noncarbohydrate diet (70% of calories as corn oil and 30% as sodium caseinate) each without and with folic acid (5 mg three times per day). The effect of insulin was studied only on the carbohydrate diet plus folic acid. Our data demonstrate that obese adult-onset diabetic patients have an impaired adaptive response of jejunal carbohydrate-metabolizing enzyme activities (hexokinase, pyruvate kinase, fructose-1-6-diphosphate aldolase, fructosediphosphatase) to dietary carbohydrate, oral folic acid, and insulin when compared to normal subjects and nondiabetic obese patients. Following a 30-day fast, the obese diabetic patients showed an improvement in glucose tolerance, hyperinsulinemia, and the adaptive response of the jejunal carbohydrate-metabolizing enzyme activities to dietary carbohydrate, folic acid, and insulin. The greatest improvement in the adaptive response of the jejunal enzyme activities occurred on the carbohydrate diet.", "contents": "Improvement in jejunal enzyme adaptation in obese adult-onset diabetic patients following a 30-day fast. The adaptive responses of gastrointestinal enzymes, glucose tolerance, and plasma insulin to diet, folic acid, and insulin of five obese adult-onset diabetic patients were studied before and after a 30-day fast. Their data were compared to the adaptive responses of gastrointestinal enzymes to diet, folic acid, and insulin of 15 normal male volunteer subjects, ages 18 to 24. Each group during each testing period received a carbohydrate diet (50% calories as carbohydrate consisting of 1/2 glucose and 1/2 fructose) and a noncarbohydrate diet (70% of calories as corn oil and 30% as sodium caseinate) each without and with folic acid (5 mg three times per day). The effect of insulin was studied only on the carbohydrate diet plus folic acid. Our data demonstrate that obese adult-onset diabetic patients have an impaired adaptive response of jejunal carbohydrate-metabolizing enzyme activities (hexokinase, pyruvate kinase, fructose-1-6-diphosphate aldolase, fructosediphosphatase) to dietary carbohydrate, oral folic acid, and insulin when compared to normal subjects and nondiabetic obese patients. Following a 30-day fast, the obese diabetic patients showed an improvement in glucose tolerance, hyperinsulinemia, and the adaptive response of the jejunal carbohydrate-metabolizing enzyme activities to dietary carbohydrate, folic acid, and insulin. The greatest improvement in the adaptive response of the jejunal enzyme activities occurred on the carbohydrate diet."} {"id": "PMID:183495", "title": "Pseudohomozygous and pseudoheterozygous type II hyperlipoproteinemia.", "content": "A 4-year-old boy had typical features of homozygous type II hyperlipoproteinemia with planar xanthomas, a plasma cholesterol level greater than 600 mg/dl, and an estimated beta-lipoprotein cholesterol concentration greater than 500 mg/dl. Both he and his sister, who had the biochemical features of the heterozygous state, responded unusually well to a diet low in saturated fat and cholesterol content. These features, combined with the finding of normocholesterolemic parents, are highly suggestive of a newly described syndrome. pseudohomozygous type II hyperlipoproteinemia.", "contents": "Pseudohomozygous and pseudoheterozygous type II hyperlipoproteinemia. A 4-year-old boy had typical features of homozygous type II hyperlipoproteinemia with planar xanthomas, a plasma cholesterol level greater than 600 mg/dl, and an estimated beta-lipoprotein cholesterol concentration greater than 500 mg/dl. Both he and his sister, who had the biochemical features of the heterozygous state, responded unusually well to a diet low in saturated fat and cholesterol content. These features, combined with the finding of normocholesterolemic parents, are highly suggestive of a newly described syndrome. pseudohomozygous type II hyperlipoproteinemia."} {"id": "PMID:183498", "title": "Effects of 13-nle-motilin on salivary, gastric, and pancreatic secretions in man.", "content": "Salivary, gastric, and pancreatic secretory responses to intravenous 13-norleucine-motilin (13-nle-motilin), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, were studied in healthy volunteers. 13-nle-Motilin in doses of 100 ng/kg body wt/hr significantly stimulated gastric pepsin output, while H + secretion and serum gastrin levels remained unchanged. Enhanced pepsin secretion was not accompanied by an increase in gastric secretion of cyclic 3', 5'-adenosine monophosphate, nor did gastric mucosal levels of the cyclic nucleotide rise. A dose of 13-nle-motilin, which stimulated gastric pepsin output, did not exert any significant effect on salivary and pancreatic secretions.", "contents": "Effects of 13-nle-motilin on salivary, gastric, and pancreatic secretions in man. Salivary, gastric, and pancreatic secretory responses to intravenous 13-norleucine-motilin (13-nle-motilin), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, were studied in healthy volunteers. 13-nle-Motilin in doses of 100 ng/kg body wt/hr significantly stimulated gastric pepsin output, while H + secretion and serum gastrin levels remained unchanged. Enhanced pepsin secretion was not accompanied by an increase in gastric secretion of cyclic 3', 5'-adenosine monophosphate, nor did gastric mucosal levels of the cyclic nucleotide rise. A dose of 13-nle-motilin, which stimulated gastric pepsin output, did not exert any significant effect on salivary and pancreatic secretions."} {"id": "PMID:183499", "title": "Diagnosis of cytomegalovirus pneumonia in compromised hosts.", "content": "Sixteen patients with cytomegalovirus pulmonary infection are described. In 11 the diagnosis was made antemortem by lung aspirate or biopsy, and in five the diagnosis was made at postmortem by typical lung histology and positive viral lung cultures. All patients were immunosuppressed by both their underlying diseases and treatment with corticosteroids and other chemotherapy. Although other pathogens were identified at lung biopsy in most patients (73 per cent), primarily Pneumocystis carinii, evidence is offered to demonstrate that cytomegalovirus can cause significant pulmonary disease alone, leading to respiratory failure and death.", "contents": "Diagnosis of cytomegalovirus pneumonia in compromised hosts. Sixteen patients with cytomegalovirus pulmonary infection are described. In 11 the diagnosis was made antemortem by lung aspirate or biopsy, and in five the diagnosis was made at postmortem by typical lung histology and positive viral lung cultures. All patients were immunosuppressed by both their underlying diseases and treatment with corticosteroids and other chemotherapy. Although other pathogens were identified at lung biopsy in most patients (73 per cent), primarily Pneumocystis carinii, evidence is offered to demonstrate that cytomegalovirus can cause significant pulmonary disease alone, leading to respiratory failure and death."} {"id": "PMID:183500", "title": "Clinical and laboratory evaluation of elderly patients with heterophil-antibody positive infectious mononucleosis. Report of seven patients, ages 40 to 78.", "content": "Clinical, hematologic, biochemical and serologic data are recorded in seven patients aged 40 to 78 years with heterophil-antibody positive infectious mononucleosis (HA+IM). Clinical observations included fever of 22 to 30 days' duration (five of seven patients), sore throat (six of seven patients), myalgia (five of seven patients) and prominent lymph adenopathy (two of seven patients). Initial blood smears revealed significant numbers of atypical lymphocytes in only five of seven patients; however, or serial testing, in the remaining two patients Downey cells developed to a degree seen in most young adult patients with infectious mononucleosis. Comparison of liver function data from these and younger patients suggests that abnormalities tend to be more marked in those in the older than in those in the younger age range. Serologic tests confirmed primary Epstein-Barr virus (EBV) infections in all seven patients based on detection of IgM antibodies to EB viral capsid antigen in specimens obtained early, but not late, in the course of the infection, transitory antibody responses to the D (diffuse) component of the EMB-induced early antigen complex, and the initial absence and later development of antibodies to the EBV-associated nuclear antigen. Thus, the serologic data did not differ from those seen in younger patients. These results show that infectious mononucleosis should be included in the differential diagnosis of fever, sore throat and myalgia with or without significant cervical adenopathy in elderly persons.", "contents": "Clinical and laboratory evaluation of elderly patients with heterophil-antibody positive infectious mononucleosis. Report of seven patients, ages 40 to 78. Clinical, hematologic, biochemical and serologic data are recorded in seven patients aged 40 to 78 years with heterophil-antibody positive infectious mononucleosis (HA+IM). Clinical observations included fever of 22 to 30 days' duration (five of seven patients), sore throat (six of seven patients), myalgia (five of seven patients) and prominent lymph adenopathy (two of seven patients). Initial blood smears revealed significant numbers of atypical lymphocytes in only five of seven patients; however, or serial testing, in the remaining two patients Downey cells developed to a degree seen in most young adult patients with infectious mononucleosis. Comparison of liver function data from these and younger patients suggests that abnormalities tend to be more marked in those in the older than in those in the younger age range. Serologic tests confirmed primary Epstein-Barr virus (EBV) infections in all seven patients based on detection of IgM antibodies to EB viral capsid antigen in specimens obtained early, but not late, in the course of the infection, transitory antibody responses to the D (diffuse) component of the EMB-induced early antigen complex, and the initial absence and later development of antibodies to the EBV-associated nuclear antigen. Thus, the serologic data did not differ from those seen in younger patients. These results show that infectious mononucleosis should be included in the differential diagnosis of fever, sore throat and myalgia with or without significant cervical adenopathy in elderly persons."} {"id": "PMID:183501", "title": "The effect of trigeminal nerve and ganglion manipulation on recurrence of ocular herpes simplex in rabbits.", "content": "Latent herpes simplex virus (HSV) has been demonstrated in the trigeminal ganglia of experimentally infected rabbits between episodes of spontaneous ocular recurrence. In three experiments reported here, the normal pattern of recurrence was modified by manipulation of the trigeminal nerve and ganglion. Temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals significantly decreased the number of ocular HSV isolations obtained during the 20 weeks immediately following surgery. Stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. In chronically infected animals, stereotaxic stimulation of the trigeminal ganglion caused a marked increase in positive cultures within 2 days. These studies provide additional evidence for the theory that the reservoir for latent ocular HSV in rabbits is the trigeminal ganglion. Moreover, the studies suggest that the transmission of latent HSV from the trigeminal ganglion to its infectious form in the peripheral tissues involves the trigeminal nerve. We have shown that mechanical and stereotaxic stimulation of the trigeminal ganglion is a reliable and rapid means of precipitating peripheral ocular shedding of HSV on command, a finding which should prove most productive in future research.", "contents": "The effect of trigeminal nerve and ganglion manipulation on recurrence of ocular herpes simplex in rabbits. Latent herpes simplex virus (HSV) has been demonstrated in the trigeminal ganglia of experimentally infected rabbits between episodes of spontaneous ocular recurrence. In three experiments reported here, the normal pattern of recurrence was modified by manipulation of the trigeminal nerve and ganglion. Temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals significantly decreased the number of ocular HSV isolations obtained during the 20 weeks immediately following surgery. Stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. In chronically infected animals, stereotaxic stimulation of the trigeminal ganglion caused a marked increase in positive cultures within 2 days. These studies provide additional evidence for the theory that the reservoir for latent ocular HSV in rabbits is the trigeminal ganglion. Moreover, the studies suggest that the transmission of latent HSV from the trigeminal ganglion to its infectious form in the peripheral tissues involves the trigeminal nerve. We have shown that mechanical and stereotaxic stimulation of the trigeminal ganglion is a reliable and rapid means of precipitating peripheral ocular shedding of HSV on command, a finding which should prove most productive in future research."} {"id": "PMID:183503", "title": "Antibodies to adeno-associated satellite virus and herpes simplex in sera from cancer patients and normal adults.", "content": "The ecologic aspects of the distribution of adeno-associated satellite virus (ASV) in the human population are of great interest because of its unconditional defectiveness and dependence on adenovirus for full and herpesvirus for partial complementation. Adenoviruses and herpesviruses are extremely common and persistent infections in man. We have developed immunofluorescent procedures for detecting the presence of satellite virus antibodies in human sera. The percentage of sera with antibodies to the ASV 2-3 complex was significantly higher in the normal group than in the cancer patients whereas there were no significant differences in herpes antibodies between the groups. The low incidence of satellite antibodies was particularly striking in patients with genital malignancies. The role of ASV's in human disease is not known. Their role in possible abrogation of oncogenesis mediated through adenoviruses or herpesviruses is worthy of further investigation.", "contents": "Antibodies to adeno-associated satellite virus and herpes simplex in sera from cancer patients and normal adults. The ecologic aspects of the distribution of adeno-associated satellite virus (ASV) in the human population are of great interest because of its unconditional defectiveness and dependence on adenovirus for full and herpesvirus for partial complementation. Adenoviruses and herpesviruses are extremely common and persistent infections in man. We have developed immunofluorescent procedures for detecting the presence of satellite virus antibodies in human sera. The percentage of sera with antibodies to the ASV 2-3 complex was significantly higher in the normal group than in the cancer patients whereas there were no significant differences in herpes antibodies between the groups. The low incidence of satellite antibodies was particularly striking in patients with genital malignancies. The role of ASV's in human disease is not known. Their role in possible abrogation of oncogenesis mediated through adenoviruses or herpesviruses is worthy of further investigation."} {"id": "PMID:183504", "title": "The significance of measurement of human placental lactogen, human chorionic gonadotropin, and carcinoembryonic antigen in patients with ovarian carcinoma.", "content": "Human placental lactogen (HPL or HCS), the beta subunit of human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were measured by a specific radioimmunoassay in plasma of 65 patients with ovarian cancer. Fifty-one patients had epithelial tumors, while 14 had germ cell tumors. It was found that 47 patients (72 per cent) had high levels of plasma HPL, 29 patients (45 per cent) had high levels of plasma beta-HCG, and 34 patients (52 per cent) had high levels of plasma CEA, but there was no correlation between these protein marker levels in different patients. Twenty of these patients were studied before and after operation and during chemotherapy and/or radiotherpy. There was no consistent correlation between these marker levels and the course of the disease. These data suggest that measurement of HPL, beta-HCG, and CEA in sera of patients with ovarian cancer is not of value in assessing the clinical status of the patients or in determining the effect of therapy.", "contents": "The significance of measurement of human placental lactogen, human chorionic gonadotropin, and carcinoembryonic antigen in patients with ovarian carcinoma. Human placental lactogen (HPL or HCS), the beta subunit of human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were measured by a specific radioimmunoassay in plasma of 65 patients with ovarian cancer. Fifty-one patients had epithelial tumors, while 14 had germ cell tumors. It was found that 47 patients (72 per cent) had high levels of plasma HPL, 29 patients (45 per cent) had high levels of plasma beta-HCG, and 34 patients (52 per cent) had high levels of plasma CEA, but there was no correlation between these protein marker levels in different patients. Twenty of these patients were studied before and after operation and during chemotherapy and/or radiotherpy. There was no consistent correlation between these marker levels and the course of the disease. These data suggest that measurement of HPL, beta-HCG, and CEA in sera of patients with ovarian cancer is not of value in assessing the clinical status of the patients or in determining the effect of therapy."} {"id": "PMID:183505", "title": "Spontaneous rupture of the liver in pregnancy: a report of eight cases.", "content": "Seven cases of ruptured subcapsular hematoma and one case of ruptured hepatoma are reported. Six of the patients died, four following an unsuccessful operation. One patient survived following an operation, and another patient survived without surgical intervention. Both survivors were treated with a gravity suit to control internal hemorrhage.", "contents": "Spontaneous rupture of the liver in pregnancy: a report of eight cases. Seven cases of ruptured subcapsular hematoma and one case of ruptured hepatoma are reported. Six of the patients died, four following an unsuccessful operation. One patient survived following an operation, and another patient survived without surgical intervention. Both survivors were treated with a gravity suit to control internal hemorrhage."} {"id": "PMID:183506", "title": "An in vitro model of pancreatic carcinoma. Morphology and in vivo growth.", "content": "Pancreas rudiments from 13-day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 weeks. Pancreas morphogenesis and differentiation occurred during the first week of culture. Acinar cell degeneration and necrosis began on the fifth day of culture and resulted in almost complete loss of acinar cells, islet cells, and fibroblasts by the end of the third week. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal, or undifferentiated?). Theses cells formed glandular structures which extended to the surface of the explant. By the end of the fourth week, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 weeks of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia; and 3%, acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10-week-old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction.", "contents": "An in vitro model of pancreatic carcinoma. Morphology and in vivo growth. Pancreas rudiments from 13-day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 weeks. Pancreas morphogenesis and differentiation occurred during the first week of culture. Acinar cell degeneration and necrosis began on the fifth day of culture and resulted in almost complete loss of acinar cells, islet cells, and fibroblasts by the end of the third week. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal, or undifferentiated?). Theses cells formed glandular structures which extended to the surface of the explant. By the end of the fourth week, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 weeks of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia; and 3%, acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10-week-old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction."} {"id": "PMID:183507", "title": "Identification of T and B lymphocytes in human breast cancer with immunohistochemical techniques.", "content": "Cryostat sections of 50 breast cancer specimens and several lymphoid organs were investigated with antisera against human T-lymphocyte antigen, human lymphocytes, and human immunoglobulins using the immunofluorescence technique and the immunoperoxidase technique. These methods proved to make it possible to discriminate between T and B cells in lymphocytic infiltrates in tissue sections. In nearly all mammary carcinomas studied, T cells were found to predominate in and around tumor cell nests. Only the intraductal carcinomas of this series contained a substantial number of B cells in addition to T cells. The presence of T cells indicates that the host-tumor interaction in vivo mall-mediated immune reaction. The role of the B cells found in the lymphocytic infiltrates of the intraductal carcinomas is still a matter of speculation. Moreover, these findings enhance the value of established histologic classifications. These classifications may have to be modified to provide them with a more functional basis.", "contents": "Identification of T and B lymphocytes in human breast cancer with immunohistochemical techniques. Cryostat sections of 50 breast cancer specimens and several lymphoid organs were investigated with antisera against human T-lymphocyte antigen, human lymphocytes, and human immunoglobulins using the immunofluorescence technique and the immunoperoxidase technique. These methods proved to make it possible to discriminate between T and B cells in lymphocytic infiltrates in tissue sections. In nearly all mammary carcinomas studied, T cells were found to predominate in and around tumor cell nests. Only the intraductal carcinomas of this series contained a substantial number of B cells in addition to T cells. The presence of T cells indicates that the host-tumor interaction in vivo mall-mediated immune reaction. The role of the B cells found in the lymphocytic infiltrates of the intraductal carcinomas is still a matter of speculation. Moreover, these findings enhance the value of established histologic classifications. These classifications may have to be modified to provide them with a more functional basis."} {"id": "PMID:183508", "title": "Metabolic activity of brown adipose tissue in T3-treated hamsters.", "content": "Triiodothyronine (T3) treatment induced marked hypertrophy of the brown adipose tissue (BAT), similar to that observed in cold-acclimated animals, although partly due to fat deposition. Similar to cold acclimation, T3 treatment also increased the oxidation of succinate by tissue slices without concomitant increase in isolated mitochondria. It is therefore suggested that thyroid hormones, like cold acclimation, effect conformational changes in the mitochondria, leading to greater expression of the succinic oxidase in the tissue. T3 treatment was not followed by any change in the respiratory activity of tissue slices in the presence of alpha-GP. Likewise, no change was found either in other oxidative activities tested in isolated mitochondria (e.g., NADH and cytochrome oxidases) or in the concentration of the components of the electron transport chain in the mitochondria.", "contents": "Metabolic activity of brown adipose tissue in T3-treated hamsters. Triiodothyronine (T3) treatment induced marked hypertrophy of the brown adipose tissue (BAT), similar to that observed in cold-acclimated animals, although partly due to fat deposition. Similar to cold acclimation, T3 treatment also increased the oxidation of succinate by tissue slices without concomitant increase in isolated mitochondria. It is therefore suggested that thyroid hormones, like cold acclimation, effect conformational changes in the mitochondria, leading to greater expression of the succinic oxidase in the tissue. T3 treatment was not followed by any change in the respiratory activity of tissue slices in the presence of alpha-GP. Likewise, no change was found either in other oxidative activities tested in isolated mitochondria (e.g., NADH and cytochrome oxidases) or in the concentration of the components of the electron transport chain in the mitochondria."} {"id": "PMID:183509", "title": "Hormone-stimulated glycogenolysis in isolated goldfish hepatocytes.", "content": "Hepatocytes isolated from the liver of the common goldfish Carassius auratus L. with crude bacterial collagenase maintained ATP levels for at least 2 h. Glycogenolysis was maximally activated by 1 X 10(-6) M epinephrine and 5.8 X 10(-9) M glucagon. In liver cells incubated in calcium-free buffer containing 1 mM ethylene glycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, basal glycogenolysis was enhanced by the addition of 1-4 mM calcium but the elevation of cyclic AMP and glycogenolysis due to epinephrine was unaffected by calcium. The divalent cation ionophore A23187 did not alter basal or hormone-stimulated glycogenolysis. Isoproterenol was approximately as potent as epinephrine but phenylephrine was glycogenolytic only at very high concentrations. l-Propranolol competitively inhibited the increased glycogenolysis due to catecholamines but phentolamine was ineffective as a blocking agent. Isoproterenol and epinephrine stimulated glycogenolysis at lower concentrations than those required to elevate cyclic AMP accumulation. Phenylephrine was without effect on cyclic AMP. Propranolol competitively inhibited both epinephrine- and isoproterenol-stimulated cyclic AMP accumulation, but phentolamine did not block either response. Catecholamine-stimulated glycogenolysis in goldfish liver is apparently a beta-adrenergic effect. However, low concentrations of epinephrine enhance glycogenolysis without affecting total cyclic AMP.", "contents": "Hormone-stimulated glycogenolysis in isolated goldfish hepatocytes. Hepatocytes isolated from the liver of the common goldfish Carassius auratus L. with crude bacterial collagenase maintained ATP levels for at least 2 h. Glycogenolysis was maximally activated by 1 X 10(-6) M epinephrine and 5.8 X 10(-9) M glucagon. In liver cells incubated in calcium-free buffer containing 1 mM ethylene glycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, basal glycogenolysis was enhanced by the addition of 1-4 mM calcium but the elevation of cyclic AMP and glycogenolysis due to epinephrine was unaffected by calcium. The divalent cation ionophore A23187 did not alter basal or hormone-stimulated glycogenolysis. Isoproterenol was approximately as potent as epinephrine but phenylephrine was glycogenolytic only at very high concentrations. l-Propranolol competitively inhibited the increased glycogenolysis due to catecholamines but phentolamine was ineffective as a blocking agent. Isoproterenol and epinephrine stimulated glycogenolysis at lower concentrations than those required to elevate cyclic AMP accumulation. Phenylephrine was without effect on cyclic AMP. Propranolol competitively inhibited both epinephrine- and isoproterenol-stimulated cyclic AMP accumulation, but phentolamine did not block either response. Catecholamine-stimulated glycogenolysis in goldfish liver is apparently a beta-adrenergic effect. However, low concentrations of epinephrine enhance glycogenolysis without affecting total cyclic AMP."} {"id": "PMID:183510", "title": "Intestinal mucosal cyclic GMP: regulation and relation to ion transport.", "content": "Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven.", "contents": "Intestinal mucosal cyclic GMP: regulation and relation to ion transport. Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven."} {"id": "PMID:183511", "title": "Hyperpolarization of thyroid cells in vitro by thyrotropin and cyclic AMP.", "content": "With the use of microelectrodes, membrane potential (MP) was measured in mouse thyroid glands in vitro. A basal resting MP of about -39 mV was confirmed. The initial effect of feeding a low-iodine diet (6-12 days) was hyperpolarization, up to -47 m V; chronic low-iodine diet led to depolarization. Low concentrations of thyrotropin (less than 3 mU/ml superfusate) caused hyperpolarization and high ones (greater than 10 mU/ml) led to depolarization. Cyclic AMP (10(-3) M), dibutyryl cyclic AMP (1.2 X 10(-4) M or 1.2 X 10(-3) M) and theophylline (10(-2) or 10(-3) M) caused similar hyperpolarization: D- and DL-propranolol (5 X 10(-5) -5 X 10(-4) M) produced depolarization and inhibited hyperpolarization by thyrotropin. Conclusions are that hyperpolarization is a consequence of short-term increased secretion of thyrotropin in vivo or of low (near physiological) concentrations in vitro; these effects are probably mediated by cyclic AMP. The relationship to and mechanism of depolarization resulting from chronic enhanced endogenous secretion or high in vitro concentrations of thyrotropin are unknown.", "contents": "Hyperpolarization of thyroid cells in vitro by thyrotropin and cyclic AMP. With the use of microelectrodes, membrane potential (MP) was measured in mouse thyroid glands in vitro. A basal resting MP of about -39 mV was confirmed. The initial effect of feeding a low-iodine diet (6-12 days) was hyperpolarization, up to -47 m V; chronic low-iodine diet led to depolarization. Low concentrations of thyrotropin (less than 3 mU/ml superfusate) caused hyperpolarization and high ones (greater than 10 mU/ml) led to depolarization. Cyclic AMP (10(-3) M), dibutyryl cyclic AMP (1.2 X 10(-4) M or 1.2 X 10(-3) M) and theophylline (10(-2) or 10(-3) M) caused similar hyperpolarization: D- and DL-propranolol (5 X 10(-5) -5 X 10(-4) M) produced depolarization and inhibited hyperpolarization by thyrotropin. Conclusions are that hyperpolarization is a consequence of short-term increased secretion of thyrotropin in vivo or of low (near physiological) concentrations in vitro; these effects are probably mediated by cyclic AMP. The relationship to and mechanism of depolarization resulting from chronic enhanced endogenous secretion or high in vitro concentrations of thyrotropin are unknown."} {"id": "PMID:183512", "title": "Effect of colchicine on urinary phosphate and regulation by parathyroid hormone.", "content": "The possible role of cytoplasmic microtubules in the renal handling of phosphate and its regulation by parathyroid hormone (PTH) was evaluated with colchicine, a microtubule-disrupting agent. Colchicine-treated rats were thyroparathyroidectomized (TPTX) and subsequently infused with PTH. Treatment with a total dose of 1 mg colchicine had no effect on glomerular filtration rate or fractional excretions of sodium and potassium. Fractional excretion of phosphate in colchicine-treated TPTX rats was significantly higher compared with TPTX controls. After PTH infusion, control rats responded with increases in fractional excretion of phosphate and urinary cyclic AMP but colchicine-treated rats had variable and insignificant changes in both parameters. Fractional excretion of sodium and potassium did not change significantly after PTH. Renal cortical activities of cyclic AMP phosphodiesterase, soluble alkaline phosphatase, cytochrome oxidase, leucine aminopeptidase, or basal adenylate cyclase were not significantly affected by colchicine treatment. On the other hand, stimulation of adenylate cyclase by a submaximal dose of PTH was markedly decreased in colchicine-treated rats, and the activity of membrane-bound alkaline phosphatase was also significantly decreased. The binding of radioactive colchicine in renal cortical extracts from rats treated with colchicine was significantly diminished. These results suggest that disruption of cytoplasmic microtubules in renal cortical cells interferes with phosphate transport and its regulation by PTH.", "contents": "Effect of colchicine on urinary phosphate and regulation by parathyroid hormone. The possible role of cytoplasmic microtubules in the renal handling of phosphate and its regulation by parathyroid hormone (PTH) was evaluated with colchicine, a microtubule-disrupting agent. Colchicine-treated rats were thyroparathyroidectomized (TPTX) and subsequently infused with PTH. Treatment with a total dose of 1 mg colchicine had no effect on glomerular filtration rate or fractional excretions of sodium and potassium. Fractional excretion of phosphate in colchicine-treated TPTX rats was significantly higher compared with TPTX controls. After PTH infusion, control rats responded with increases in fractional excretion of phosphate and urinary cyclic AMP but colchicine-treated rats had variable and insignificant changes in both parameters. Fractional excretion of sodium and potassium did not change significantly after PTH. Renal cortical activities of cyclic AMP phosphodiesterase, soluble alkaline phosphatase, cytochrome oxidase, leucine aminopeptidase, or basal adenylate cyclase were not significantly affected by colchicine treatment. On the other hand, stimulation of adenylate cyclase by a submaximal dose of PTH was markedly decreased in colchicine-treated rats, and the activity of membrane-bound alkaline phosphatase was also significantly decreased. The binding of radioactive colchicine in renal cortical extracts from rats treated with colchicine was significantly diminished. These results suggest that disruption of cytoplasmic microtubules in renal cortical cells interferes with phosphate transport and its regulation by PTH."} {"id": "PMID:183513", "title": "RENAL HANDLING OF CITRATE DURING HEAT-INDUCED HYPOCITRICEMIA.", "content": "A model of steady-state hypocitricemia, characterized by hypocitraturia and reduced kidney cortex citrate, has been demonstrated in the rate chronically exposed to environmental heat. The renal citrate extraction ratio remains unchanged. The physiological mechanism that brings about the reduction in circulating citrate has not been determined. Hypocitraturia likely results from a decreased filtered citrate load. Although it is generally contended that filtered citrate load. Although it is generally contended that alkalosis increases and acidosis decreases renal excretion of citrate, observations of mild alkalosis and hypocitraturia during heat exposure suggest that factors other than pH can alter renal handling of citrate. Kidney mitochondrial function, as determined by in vitro measurements of citrate-stimulated respiratory rates and specific activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and cytochrome c oxidase, appears to be unaffected by environmental heat.", "contents": "RENAL HANDLING OF CITRATE DURING HEAT-INDUCED HYPOCITRICEMIA. A model of steady-state hypocitricemia, characterized by hypocitraturia and reduced kidney cortex citrate, has been demonstrated in the rate chronically exposed to environmental heat. The renal citrate extraction ratio remains unchanged. The physiological mechanism that brings about the reduction in circulating citrate has not been determined. Hypocitraturia likely results from a decreased filtered citrate load. Although it is generally contended that filtered citrate load. Although it is generally contended that alkalosis increases and acidosis decreases renal excretion of citrate, observations of mild alkalosis and hypocitraturia during heat exposure suggest that factors other than pH can alter renal handling of citrate. Kidney mitochondrial function, as determined by in vitro measurements of citrate-stimulated respiratory rates and specific activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and cytochrome c oxidase, appears to be unaffected by environmental heat."} {"id": "PMID:183514", "title": "Agonist and antimineralocorticoid activities of spirolactones.", "content": "To investigate the mechanism of action of antimineralocorticoids, a series of spirolactone analogues was evaluated for both mineralocorticoid antagonist and agonist activity. Antagonist activity was assessed by inhibition of aldosterone stimulated sodium transport employing toad bladder short-circuit current (SCC) measurements. Agonist activity was assessed in the same system by the direct effect of spirolactones on SCC. Opening of the gamma-lactone ring of a spirolactone dramatically decreased antagonist activity in the compound studied. Several C-7 chi-substitutions resulted in either enhanced or diminished activity, whereas deletion of the C-10 methyl group (i.e., 19-nor compound) had only minimal effects on antagonist potency. Agonist activity was demonstrable for three of the analogues studied: the 19-nor compound, and those containing a C-7 chi-substitution with a carboxyl isopropyl ester or a C-6-7 cyclopropyl linkage. The functional activity in toad bladder was compared to previous measurements of the relative binding affinity of the same spirolactones for mineralocorticoid receptors in rat kidney. Although there was some correlation between binding to rat kidney receptors and antagonist activity in the toad bladder, the results did not coincide in the case of the three spirolactones that possessed partial agonist activity. Some of the discrepancy may have resulted from differences between mammalian and amphibian receptors; however, intrinsic agonist activity limits antagonist potency and thus may cause a divergence between binding and functional studies limited to antagonist activity alone. Binding affinity, although indicative of total activity, fails to distinguish agonist from antagonist potency.", "contents": "Agonist and antimineralocorticoid activities of spirolactones. To investigate the mechanism of action of antimineralocorticoids, a series of spirolactone analogues was evaluated for both mineralocorticoid antagonist and agonist activity. Antagonist activity was assessed by inhibition of aldosterone stimulated sodium transport employing toad bladder short-circuit current (SCC) measurements. Agonist activity was assessed in the same system by the direct effect of spirolactones on SCC. Opening of the gamma-lactone ring of a spirolactone dramatically decreased antagonist activity in the compound studied. Several C-7 chi-substitutions resulted in either enhanced or diminished activity, whereas deletion of the C-10 methyl group (i.e., 19-nor compound) had only minimal effects on antagonist potency. Agonist activity was demonstrable for three of the analogues studied: the 19-nor compound, and those containing a C-7 chi-substitution with a carboxyl isopropyl ester or a C-6-7 cyclopropyl linkage. The functional activity in toad bladder was compared to previous measurements of the relative binding affinity of the same spirolactones for mineralocorticoid receptors in rat kidney. Although there was some correlation between binding to rat kidney receptors and antagonist activity in the toad bladder, the results did not coincide in the case of the three spirolactones that possessed partial agonist activity. Some of the discrepancy may have resulted from differences between mammalian and amphibian receptors; however, intrinsic agonist activity limits antagonist potency and thus may cause a divergence between binding and functional studies limited to antagonist activity alone. Binding affinity, although indicative of total activity, fails to distinguish agonist from antagonist potency."} {"id": "PMID:183515", "title": "Effect of norepinephrine and hypertonicity on K influx and cyclic AMP in duck erythrocytes.", "content": "Cyclic adenosine 3',5'-monophosphate (cAMP) accumulation and cation transport were measured in duck erythrocytes after stimulation by norepinephrine (NE) or shrinkage induced by exposure to hypertonic media (S). Previously both NE and S were shown to initiate a similar transport process in this cell. NE elicited a rapid rise in cellular cAMP and 42K influx. Both effects were eliminated by propranolol. At concentrations of NE below 3 X 10(-8) M (the concentration at which 42K influx saturates), there was good correlation between the magnitude of the permeability change and the increment in cAMP. In contrast, medium hypertonicity, at a level which stimulated K influx to the same extent as a near-maximal norepinephrine response, did not alter cAMP content. The data are discussed in terms of a model in which S and NE activate a final common transport pathway by different mechanisms, which in the case of S does not involve cAMP.", "contents": "Effect of norepinephrine and hypertonicity on K influx and cyclic AMP in duck erythrocytes. Cyclic adenosine 3',5'-monophosphate (cAMP) accumulation and cation transport were measured in duck erythrocytes after stimulation by norepinephrine (NE) or shrinkage induced by exposure to hypertonic media (S). Previously both NE and S were shown to initiate a similar transport process in this cell. NE elicited a rapid rise in cellular cAMP and 42K influx. Both effects were eliminated by propranolol. At concentrations of NE below 3 X 10(-8) M (the concentration at which 42K influx saturates), there was good correlation between the magnitude of the permeability change and the increment in cAMP. In contrast, medium hypertonicity, at a level which stimulated K influx to the same extent as a near-maximal norepinephrine response, did not alter cAMP content. The data are discussed in terms of a model in which S and NE activate a final common transport pathway by different mechanisms, which in the case of S does not involve cAMP."} {"id": "PMID:183516", "title": "Compensatory adrenal growth: a neurally mediated reflex.", "content": "The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adreanl at 12 h resulted in an enlarged right adrenal at 12h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement at 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.", "contents": "Compensatory adrenal growth: a neurally mediated reflex. The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adreanl at 12 h resulted in an enlarged right adrenal at 12h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement at 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex."} {"id": "PMID:183518", "title": "High dose urography: incidence and relationship to spontaneous peripelvic extravasation.", "content": "A prospective study was undertaken to determine the incidence of spontaneous extravasation of contrast in 82 patients with acute renal colic. The extravasation rate among 37 patients receiving 75 ml of contrast was 8.1%, while the rate among 45 patients receiving either 300 ml of 30% solution by infusion or a 140 ml bolus dose was 24.4%; overall the rate was 17%. Thus the incidence of extravasation was shown to increase with higher doses of contrast media. The primary dose in acute renal colic or other forms of obstructive uropathy should be in the low range (20-25 g 1-); reinjection after screening can be undertaken if necessary.", "contents": "High dose urography: incidence and relationship to spontaneous peripelvic extravasation. A prospective study was undertaken to determine the incidence of spontaneous extravasation of contrast in 82 patients with acute renal colic. The extravasation rate among 37 patients receiving 75 ml of contrast was 8.1%, while the rate among 45 patients receiving either 300 ml of 30% solution by infusion or a 140 ml bolus dose was 24.4%; overall the rate was 17%. Thus the incidence of extravasation was shown to increase with higher doses of contrast media. The primary dose in acute renal colic or other forms of obstructive uropathy should be in the low range (20-25 g 1-); reinjection after screening can be undertaken if necessary."} {"id": "PMID:183519", "title": "Autonomous hyperparathyroidism in patients on maintenance home dialysis.", "content": "Ninety-nine patients with end-stage renal failure treated by maintenance home dialysis whose calcium and phosphorus balance was carefully controlled were studied for radiographic evidence of hyperparathyroidism. A total of 43 showed evidence of hyperparathyroidism despite excellent medical management. In 23 the abnormality was stable and the patients were asymptomatic with regard to the skeleton. The other 20 showed progressive bone disease. Sixteen of these patients were operated upon, and 14 were relieved of their symptoms by parathyroidectomy. Following operation, the radiographic evidence of bone disease halted dramatically, and a decided return toward normal was documented on subsequent films. Thus parathyroidectomy can control the skeletal deterioration and bone pain of hyperparathyroidism in patients who develop this complication. Serial radiographic studies are a reliable indicator of this circumstance.", "contents": "Autonomous hyperparathyroidism in patients on maintenance home dialysis. Ninety-nine patients with end-stage renal failure treated by maintenance home dialysis whose calcium and phosphorus balance was carefully controlled were studied for radiographic evidence of hyperparathyroidism. A total of 43 showed evidence of hyperparathyroidism despite excellent medical management. In 23 the abnormality was stable and the patients were asymptomatic with regard to the skeleton. The other 20 showed progressive bone disease. Sixteen of these patients were operated upon, and 14 were relieved of their symptoms by parathyroidectomy. Following operation, the radiographic evidence of bone disease halted dramatically, and a decided return toward normal was documented on subsequent films. Thus parathyroidectomy can control the skeletal deterioration and bone pain of hyperparathyroidism in patients who develop this complication. Serial radiographic studies are a reliable indicator of this circumstance."} {"id": "PMID:183520", "title": "Therapeutic vascular occlusion utilizing steel coil technique: clinical applications.", "content": "The stainless steel coil has been utilized for permanent intravascular occlusion of the proximal portion of the renal, hepatic, splenic, and internal iliac vessels. This therapeutic approach has been successful in the management of renal arteriovenous fistulas, renal carcinomas, neoplasms of the liver, giant cell tumors of the sacrum, and in hypersplenism. The techniques involved and clinical uses are discussed.", "contents": "Therapeutic vascular occlusion utilizing steel coil technique: clinical applications. The stainless steel coil has been utilized for permanent intravascular occlusion of the proximal portion of the renal, hepatic, splenic, and internal iliac vessels. This therapeutic approach has been successful in the management of renal arteriovenous fistulas, renal carcinomas, neoplasms of the liver, giant cell tumors of the sacrum, and in hypersplenism. The techniques involved and clinical uses are discussed."} {"id": "PMID:183521", "title": "Embolic control of hypertension caused by segmental renal artery stenosis.", "content": "Renovascular hypertension was controlled in a 15-year-old boy by total infarction of the renal parenchyma behind a segmental renal artery stenosis. Two separate embolizations were required to occlude the branches distal to the stenosis. Blood pressure did not return to normal until after the second procedure. This approach may be useful in patients with intrarenal arterial stenoses who would be difficult to approach operatively without sacrificing a significant portion of the kidney.", "contents": "Embolic control of hypertension caused by segmental renal artery stenosis. Renovascular hypertension was controlled in a 15-year-old boy by total infarction of the renal parenchyma behind a segmental renal artery stenosis. Two separate embolizations were required to occlude the branches distal to the stenosis. Blood pressure did not return to normal until after the second procedure. This approach may be useful in patients with intrarenal arterial stenoses who would be difficult to approach operatively without sacrificing a significant portion of the kidney."} {"id": "PMID:183522", "title": "Aneurysms secondary to pancreatitis.", "content": "In a review of arteriograms of 72 unselected consecutive cases of pancreatitis, seven patients were found to have arterial aneurysms involving branches of the peripancreatic vessels. During the same period, arteriograms of 84 cases of carcinoma of the pancreas were reviewed and no aneurysms of any of these vessels were found. The demonstration of aneurysms of the peripancreatic arteries in pancreatitis is an important differential feature from carcinoma of the pancreas. Both carcinoma of the pancreas and chronic pancreatitis can cause encasement of the arterial vessels and obstruction of the splenic or the superior mesenteric vein, therefore resulting in a similar angiographic appearance. Thus an aneurysm seen in such a patient is a helpful distinguishing feature. In addition, these aneurysms are an important source of hemorrhage and mortality in pancreatitis.", "contents": "Aneurysms secondary to pancreatitis. In a review of arteriograms of 72 unselected consecutive cases of pancreatitis, seven patients were found to have arterial aneurysms involving branches of the peripancreatic vessels. During the same period, arteriograms of 84 cases of carcinoma of the pancreas were reviewed and no aneurysms of any of these vessels were found. The demonstration of aneurysms of the peripancreatic arteries in pancreatitis is an important differential feature from carcinoma of the pancreas. Both carcinoma of the pancreas and chronic pancreatitis can cause encasement of the arterial vessels and obstruction of the splenic or the superior mesenteric vein, therefore resulting in a similar angiographic appearance. Thus an aneurysm seen in such a patient is a helpful distinguishing feature. In addition, these aneurysms are an important source of hemorrhage and mortality in pancreatitis."} {"id": "PMID:183523", "title": "Radiologic and pathologic characteristics of the WDHA syndrome.", "content": "A case of a non-beta islet cell tumor of the pancreas that produced the WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome is presented. An enlarged body-tail region of the pancreas is demonstrated on transaxial views; multiple fluid-filled loops of small and large bowel are also noted. The angiography of the tumor is similar to other non-beta islet cell lesions consisting of a large hypervascular mass with hypertrophied feeding vessels and a persistent, dense capillary stain. The demonstration of elevated levels of vasoactive intestinal polypeptide in both tumor and plasma and the ultrastructural description of endocrine granules may help to explain the pathophysiology in this case.", "contents": "Radiologic and pathologic characteristics of the WDHA syndrome. A case of a non-beta islet cell tumor of the pancreas that produced the WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome is presented. An enlarged body-tail region of the pancreas is demonstrated on transaxial views; multiple fluid-filled loops of small and large bowel are also noted. The angiography of the tumor is similar to other non-beta islet cell lesions consisting of a large hypervascular mass with hypertrophied feeding vessels and a persistent, dense capillary stain. The demonstration of elevated levels of vasoactive intestinal polypeptide in both tumor and plasma and the ultrastructural description of endocrine granules may help to explain the pathophysiology in this case."} {"id": "PMID:183524", "title": "Fine needle transhepatic cholangiography: a new approach to obstructive jaundice.", "content": "Transhepatic cholangiography performed with a newly introduced fine caliber (0.7 mm OD) \"Chiba\" needle produces a significantly higher success rate of biliary duct opacification with fewer complications than conventional needle or flexible cannula techniques. Distinct advantages over endoscopic retrograde cholangiography are also apparent, including more frequent bile duct opacification, ease of performance, and lower overall cost. In a group of 50 consecutive patients examined with the fine needle puncture technique, duct opacification was achieved in 92%, including 33 of 33 (100%) of patients with surgically obstructed ducts and 14 of 17 (82%) with normal caliber or narrowed ducts. Fine needle hepatic puncture is recommended as the preferred approach for direct biliary duct opacification in jaundiced patients.", "contents": "Fine needle transhepatic cholangiography: a new approach to obstructive jaundice. Transhepatic cholangiography performed with a newly introduced fine caliber (0.7 mm OD) \"Chiba\" needle produces a significantly higher success rate of biliary duct opacification with fewer complications than conventional needle or flexible cannula techniques. Distinct advantages over endoscopic retrograde cholangiography are also apparent, including more frequent bile duct opacification, ease of performance, and lower overall cost. In a group of 50 consecutive patients examined with the fine needle puncture technique, duct opacification was achieved in 92%, including 33 of 33 (100%) of patients with surgically obstructed ducts and 14 of 17 (82%) with normal caliber or narrowed ducts. Fine needle hepatic puncture is recommended as the preferred approach for direct biliary duct opacification in jaundiced patients."} {"id": "PMID:183525", "title": "Percutaneous transhepatic cholangiography with selective catheterization of the common bile duct.", "content": "Percutaneous transhepatic cholangiography was performed in 86 patients with juandice in whom the diagnosis could not be established by conventional means. Selective catheterization of the common bile duct was employed and cholangiograms of high quality were obtained. In cases of obstruction of the biliary passages, the catheter was left indwelling centrally in the biliary passages for external bile drainage. Thus immediate postcholangiogram surgery was not required in these patients. The procedure was successful in all 60 patients with obstructive jaundice. In 26 patients the possibility of obstruction was ruled out. Complications occurred in four patients but were not exclusively due to the procedure. The incidence of complications may be maintained at an acceptably low level if the technique is meticulously followed.", "contents": "Percutaneous transhepatic cholangiography with selective catheterization of the common bile duct. Percutaneous transhepatic cholangiography was performed in 86 patients with juandice in whom the diagnosis could not be established by conventional means. Selective catheterization of the common bile duct was employed and cholangiograms of high quality were obtained. In cases of obstruction of the biliary passages, the catheter was left indwelling centrally in the biliary passages for external bile drainage. Thus immediate postcholangiogram surgery was not required in these patients. The procedure was successful in all 60 patients with obstructive jaundice. In 26 patients the possibility of obstruction was ruled out. Complications occurred in four patients but were not exclusively due to the procedure. The incidence of complications may be maintained at an acceptably low level if the technique is meticulously followed."} {"id": "PMID:183526", "title": "Jaundice from impacted sediment in a T tube: recognition and treatment.", "content": "Encrustation of bile sediment in the proximal limb of an indwelling T tube may occlude the luman and cause jaundice. The cholangiographic appearance of this phenomenon is described. Insertion of a torque cable under fluoroscopic control can successfully disimpact the occlusion, restoring patency and relieving the jaundice.", "contents": "Jaundice from impacted sediment in a T tube: recognition and treatment. Encrustation of bile sediment in the proximal limb of an indwelling T tube may occlude the luman and cause jaundice. The cholangiographic appearance of this phenomenon is described. Insertion of a torque cable under fluoroscopic control can successfully disimpact the occlusion, restoring patency and relieving the jaundice."} {"id": "PMID:183527", "title": "The aberrant gallbladder: angiographic and radioisotopic considerations.", "content": "There are four types of aberrant gallbladder: (1) intrahepatic, (2) left-sided, (3) transverse, and (4) retrodisplaced. Five cases of the first three types are illustrated. In three of the five patients the aberrant gallbladder produced false positive liver scans which were correctly diagnosed by hepatic angiography; in one it caused the hepatic angiogram to be misinterpreted. The importance of identifying the gallbladder at hepatic angiography by observing the cystic arteries in arterial phase and the gallbladder wall stain in hepatogram phase is stressed.", "contents": "The aberrant gallbladder: angiographic and radioisotopic considerations. There are four types of aberrant gallbladder: (1) intrahepatic, (2) left-sided, (3) transverse, and (4) retrodisplaced. Five cases of the first three types are illustrated. In three of the five patients the aberrant gallbladder produced false positive liver scans which were correctly diagnosed by hepatic angiography; in one it caused the hepatic angiogram to be misinterpreted. The importance of identifying the gallbladder at hepatic angiography by observing the cystic arteries in arterial phase and the gallbladder wall stain in hepatogram phase is stressed."} {"id": "PMID:183528", "title": "Electrical stimulation for anal sphincter control in barium enema examinations: an extended trial.", "content": "The routine use in 500 consecutive patients of a barium enema cannula incorporating stimulating electrodes is described. Barium retention was improved by the electrically maintained contraction of the anal sphincter. The cannula was connected to a battery-powered control unit which provided the stimulus; pulse width was 1 msec and frequency was 20 pulses/sec. The pulse amplitude, adjusted for each patient, was in the range of 5--17V. A standard procedure was adopted throughout the trial without the use of colonic relaxants (such as anticholinergic drugs). The barium suspension and water were in stilled at body temperature. A comparison with a control series of 200 patients showed a significant reduction in the failure rate from 20% to 4%. No unpleasant side effects were encountered apart from a tingling sensation in the anal region which was expected. The principal factors contributing to failure were fecal impaction and diverticular disease.", "contents": "Electrical stimulation for anal sphincter control in barium enema examinations: an extended trial. The routine use in 500 consecutive patients of a barium enema cannula incorporating stimulating electrodes is described. Barium retention was improved by the electrically maintained contraction of the anal sphincter. The cannula was connected to a battery-powered control unit which provided the stimulus; pulse width was 1 msec and frequency was 20 pulses/sec. The pulse amplitude, adjusted for each patient, was in the range of 5--17V. A standard procedure was adopted throughout the trial without the use of colonic relaxants (such as anticholinergic drugs). The barium suspension and water were in stilled at body temperature. A comparison with a control series of 200 patients showed a significant reduction in the failure rate from 20% to 4%. No unpleasant side effects were encountered apart from a tingling sensation in the anal region which was expected. The principal factors contributing to failure were fecal impaction and diverticular disease."} {"id": "PMID:183529", "title": "Radiographic evaluation of endotracheal tube position.", "content": "A malpositioned endotracheal tube is a potential hazard to the intubated patient. Ideally, the tube tip should be 5+/-2 cm from the carina when the head and neck are in neutral position. In 92 of 100 patients studied, the carina overlay T5, T6, or T7 on portable radiographs. Therefore, even when the carina is not visible, it can be assumed that a tube tip positioned at the level of T3 or T4 is safe. The degree of neck flexion or extension at the time of radiography may be determined by evaluating the position of the mandible relative to the vertebral bodies.", "contents": "Radiographic evaluation of endotracheal tube position. A malpositioned endotracheal tube is a potential hazard to the intubated patient. Ideally, the tube tip should be 5+/-2 cm from the carina when the head and neck are in neutral position. In 92 of 100 patients studied, the carina overlay T5, T6, or T7 on portable radiographs. Therefore, even when the carina is not visible, it can be assumed that a tube tip positioned at the level of T3 or T4 is safe. The degree of neck flexion or extension at the time of radiography may be determined by evaluating the position of the mandible relative to the vertebral bodies."} {"id": "PMID:183530", "title": "Further observations on pulmonary venous varix.", "content": "Pulmonary venous varix is a well known radiographic entity. Case reports are presented to illustrate the following unusual aspects of this lesion. 1. Hypoplasia of a major pulmonary vein results in increased pulmonary blood flow through the remaining normal ipsilateral pulmonary vein. This may result in variceal enlargement of the normal vein. 2. A pulmonary venous varix may be visualized during angiocardiography but not in a routine chest radiograph. This is most common in children. 3. Elevated pulmonary venous pressure causes dilatation of the central pulmonary veins. Sudden formation of a pulmonary venous varix in a patient with mitral valvular disease may be evidence of a sudden elevation of left atrial pressure.", "contents": "Further observations on pulmonary venous varix. Pulmonary venous varix is a well known radiographic entity. Case reports are presented to illustrate the following unusual aspects of this lesion. 1. Hypoplasia of a major pulmonary vein results in increased pulmonary blood flow through the remaining normal ipsilateral pulmonary vein. This may result in variceal enlargement of the normal vein. 2. A pulmonary venous varix may be visualized during angiocardiography but not in a routine chest radiograph. This is most common in children. 3. Elevated pulmonary venous pressure causes dilatation of the central pulmonary veins. Sudden formation of a pulmonary venous varix in a patient with mitral valvular disease may be evidence of a sudden elevation of left atrial pressure."} {"id": "PMID:183531", "title": "Pulmonary metastases from benign-appearing smooth muscle tumors of the uterus.", "content": "A 42-year-old woman was found to have multiple pulmonary nodules 7 years after hysterectomy for leiomyoma. Thoracotomy revealed multiple well differentiated smooth muscle masses containing epithelial inclusions. This patient is similar to others previously reported as examples of \"multiple pulmonary fibroleiomyomatous hamartoma\" on the basis of slow-growth, benign-appearing histology, and the presence of epithelial elements. Evidence is presented which suggests that these cases represent metastasis from well differentiated leiomyosarcomas. There is a frequent association with uterine smooth-muscle tumor, cases with equally benign-appearing histology have shown lymph node metastasis, the nonmesenchymal elements have been shown to represent engulphed bits of adjacent pulmonary tissue, and the histologic di-ferentiation of benign from malignant mesenchymal tumors is known to be unreliable in some cases. Unlike more anaplastic leiomyosarcomas, this condition may be associated with few symptoms and prolonged survival despite widespread disease.", "contents": "Pulmonary metastases from benign-appearing smooth muscle tumors of the uterus. A 42-year-old woman was found to have multiple pulmonary nodules 7 years after hysterectomy for leiomyoma. Thoracotomy revealed multiple well differentiated smooth muscle masses containing epithelial inclusions. This patient is similar to others previously reported as examples of \"multiple pulmonary fibroleiomyomatous hamartoma\" on the basis of slow-growth, benign-appearing histology, and the presence of epithelial elements. Evidence is presented which suggests that these cases represent metastasis from well differentiated leiomyosarcomas. There is a frequent association with uterine smooth-muscle tumor, cases with equally benign-appearing histology have shown lymph node metastasis, the nonmesenchymal elements have been shown to represent engulphed bits of adjacent pulmonary tissue, and the histologic di-ferentiation of benign from malignant mesenchymal tumors is known to be unreliable in some cases. Unlike more anaplastic leiomyosarcomas, this condition may be associated with few symptoms and prolonged survival despite widespread disease."} {"id": "PMID:183532", "title": "Radiology of knee joint replacement.", "content": "As total knee replacement becomes more successful due to advances in surgery and bioengineering, a greater number of patients will be offered this procedure as a viable alternative to arthrodesis. Radiologic consultation will be sought for evaluation of proper alignment as well as postoperative complications such as loosening, instability, dislocation, limitation of range of motion, fracture, and infection. This evaluation may be accomplished by plain films and arthrography. Radiographic aspects of these features are discussed and illustrated.", "contents": "Radiology of knee joint replacement. As total knee replacement becomes more successful due to advances in surgery and bioengineering, a greater number of patients will be offered this procedure as a viable alternative to arthrodesis. Radiologic consultation will be sought for evaluation of proper alignment as well as postoperative complications such as loosening, instability, dislocation, limitation of range of motion, fracture, and infection. This evaluation may be accomplished by plain films and arthrography. Radiographic aspects of these features are discussed and illustrated."} {"id": "PMID:183533", "title": "Traumatic lesions of the discovertebral junction in the lumbar spine.", "content": "Lumbar discovertebral abnormalities thought to be due to endogenous or subclinical trauma were evaluated in 22 cases. These consisted of predominantly lytic areas due to intrabody disc herniation in five cases, broad zones of vertebral body sclerosis due to reactive osteitis in 11, and destruction of the vertebral endplates surrounded by diffuse sclerosis in six. Spinal biopsy and negative bacterial cultures were consistent with the diagnosis in eight cases. Follow-up roentgenograms and further clinical evaluation in the remaining 14 showed either no progression or changes consistent with trauma. Only four cases had a history of exogenous trauma. Intrabody disc herniations usually affected the upper vertebral body with characteristic sparing of the adjacent endplate. The sclerotic lesions tended to occur in the anterior portion of the vertebral body, with the inferior aspect of L4 most frequently involved. These may be confused with osteoblastic metastases, particularly if adjacent disc narrowing is minimal. The lack of progressive vertebral fragmentation helps to distinguish this condition from neuroarthropathy. Lesions characterized by destruction of the vertebral endplates and reactive sclerosis simulate infection; absence of a soft tissue mass and clinical signs of sepsis as well as lack of progression are important differential features.", "contents": "Traumatic lesions of the discovertebral junction in the lumbar spine. Lumbar discovertebral abnormalities thought to be due to endogenous or subclinical trauma were evaluated in 22 cases. These consisted of predominantly lytic areas due to intrabody disc herniation in five cases, broad zones of vertebral body sclerosis due to reactive osteitis in 11, and destruction of the vertebral endplates surrounded by diffuse sclerosis in six. Spinal biopsy and negative bacterial cultures were consistent with the diagnosis in eight cases. Follow-up roentgenograms and further clinical evaluation in the remaining 14 showed either no progression or changes consistent with trauma. Only four cases had a history of exogenous trauma. Intrabody disc herniations usually affected the upper vertebral body with characteristic sparing of the adjacent endplate. The sclerotic lesions tended to occur in the anterior portion of the vertebral body, with the inferior aspect of L4 most frequently involved. These may be confused with osteoblastic metastases, particularly if adjacent disc narrowing is minimal. The lack of progressive vertebral fragmentation helps to distinguish this condition from neuroarthropathy. Lesions characterized by destruction of the vertebral endplates and reactive sclerosis simulate infection; absence of a soft tissue mass and clinical signs of sepsis as well as lack of progression are important differential features."} {"id": "PMID:183534", "title": "Congenital dislocation of the knee.", "content": "Four cases of congenital dislocation of the knee are presented. The incidence, associated congenital anomalies, presentation, and etiology are discussed with particular attention to the roentgenographic findings.", "contents": "Congenital dislocation of the knee. Four cases of congenital dislocation of the knee are presented. The incidence, associated congenital anomalies, presentation, and etiology are discussed with particular attention to the roentgenographic findings."} {"id": "PMID:183535", "title": "The os incae.", "content": "The The os incae is an integral feature of reptilian and various mammalian skulls which demonstrate intramembranous ossification centers behind the parietal bones. In man, the interparietal portion of the occipital squamosa arises in membrane from a single ossific focus. Normally it fuses with the supraoccipital segment of the occipital squamosa. Occasionally there are multiple ossification centers in the interparietal bone which fail to fuse, resulting in one of several varieties of os incae.", "contents": "The os incae. The The os incae is an integral feature of reptilian and various mammalian skulls which demonstrate intramembranous ossification centers behind the parietal bones. In man, the interparietal portion of the occipital squamosa arises in membrane from a single ossific focus. Normally it fuses with the supraoccipital segment of the occipital squamosa. Occasionally there are multiple ossification centers in the interparietal bone which fail to fuse, resulting in one of several varieties of os incae."} {"id": "PMID:183536", "title": "A new radiographic technique for fractures of the orbit and maxilla.", "content": "A variant oblique posture of the head is described which eliminates most superimposition in radiographic examination of the orbit and maxilla. The position is simply attained without extraordinary equipment, is comfortable for the patient since there is no pressure on injured parts, and often obviates the need for planigraphy. The following injuries are demonstrated best: displacement at the frontozygomatic suture; deformity of the orbital floor and its distance from the anterior orbital rim; degree of depression of the anterior zygoma, antral wall, and alveolus; and vertical displacement of the zygomatic arch.", "contents": "A new radiographic technique for fractures of the orbit and maxilla. A variant oblique posture of the head is described which eliminates most superimposition in radiographic examination of the orbit and maxilla. The position is simply attained without extraordinary equipment, is comfortable for the patient since there is no pressure on injured parts, and often obviates the need for planigraphy. The following injuries are demonstrated best: displacement at the frontozygomatic suture; deformity of the orbital floor and its distance from the anterior orbital rim; degree of depression of the anterior zygoma, antral wall, and alveolus; and vertical displacement of the zygomatic arch."} {"id": "PMID:183537", "title": "Computed tomography and brain scintigraphy in ischemic stroke.", "content": "Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this signs should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases.", "contents": "Computed tomography and brain scintigraphy in ischemic stroke. Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this signs should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases."} {"id": "PMID:183538", "title": "Normal variants and congenital anomalies in the region of the obelion.", "content": "A number of anatomic bony variants and several congenital anomalies are known to occur at the level of the obelion, that is, in the posterior interparietal region of the head, a short distance in front of the lambda. Among them are: (1) remnants of the embryonic parietal incisura, including parietal fissure, small and large parietal fontanelle, obeliac bones, persistant midline parietal foramen, and small and large parietal foramina; (2) encephalomeningoceles and related defects, including true encephaloceles, herniation of midline intracranial cysts (diencephalic and Dandy Walker cyst), epicranial arachnoid cysts, and scalp defects with ectopic glial tissue; and (3) congenital scalp and skull defects (cutis aplasia congenita). A review of these defects is presented with some illustrative examples not previously reported.", "contents": "Normal variants and congenital anomalies in the region of the obelion. A number of anatomic bony variants and several congenital anomalies are known to occur at the level of the obelion, that is, in the posterior interparietal region of the head, a short distance in front of the lambda. Among them are: (1) remnants of the embryonic parietal incisura, including parietal fissure, small and large parietal fontanelle, obeliac bones, persistant midline parietal foramen, and small and large parietal foramina; (2) encephalomeningoceles and related defects, including true encephaloceles, herniation of midline intracranial cysts (diencephalic and Dandy Walker cyst), epicranial arachnoid cysts, and scalp defects with ectopic glial tissue; and (3) congenital scalp and skull defects (cutis aplasia congenita). A review of these defects is presented with some illustrative examples not previously reported."} {"id": "PMID:183539", "title": "The destiny of brachytherapy in oncology.", "content": "At the invitation of the American Radium Society, Pierquin reviews his very large experience with continuous low dose rate irradiation of cancer. The target volume is treated with 6,000-7,000 rad in 3-10 days at a dose rate of 30-100 rad/hr. Preference for continuous low dose rate irradiation is based on the earlier work of Jean Pierquin, Georges Richard, Claudius Regaud, and Ralston Paterson with radium sources. Afterloading techniques with iridium-192 have been substituted allowing safer and more precise placement. An accumulated experience with 5,000 patients over the past 15 years permits conclusions that the techniques are safe, easy, inexpensive, and effective for tumors accessible to direct instrumentation. Dosimetry is based on the Paris system. Standardizing upon a dose of 7,000 rad, Pierquin concludes there is an isoeffect of continuous radiation at low dose rates of 25-100 rad/hr. The differential effect on tumor versus healthy tissue is impressive even when large volumes are irradiated, as in neck adenopathy. Stemming from this experience, three trials have been carried out of low dose rate teletherapy with cobalt-60 sources in oral cavity and oropharynx tumors, delivering 7,000 rad at rates of 90-100 rad/hr. Pierquin hopes for the same very high local control rates (in the order of 95%)achieved by iridium-192 endoradiotherapy of accessible T1, T2, T3, and T4 cancers.", "contents": "The destiny of brachytherapy in oncology. At the invitation of the American Radium Society, Pierquin reviews his very large experience with continuous low dose rate irradiation of cancer. The target volume is treated with 6,000-7,000 rad in 3-10 days at a dose rate of 30-100 rad/hr. Preference for continuous low dose rate irradiation is based on the earlier work of Jean Pierquin, Georges Richard, Claudius Regaud, and Ralston Paterson with radium sources. Afterloading techniques with iridium-192 have been substituted allowing safer and more precise placement. An accumulated experience with 5,000 patients over the past 15 years permits conclusions that the techniques are safe, easy, inexpensive, and effective for tumors accessible to direct instrumentation. Dosimetry is based on the Paris system. Standardizing upon a dose of 7,000 rad, Pierquin concludes there is an isoeffect of continuous radiation at low dose rates of 25-100 rad/hr. The differential effect on tumor versus healthy tissue is impressive even when large volumes are irradiated, as in neck adenopathy. Stemming from this experience, three trials have been carried out of low dose rate teletherapy with cobalt-60 sources in oral cavity and oropharynx tumors, delivering 7,000 rad at rates of 90-100 rad/hr. Pierquin hopes for the same very high local control rates (in the order of 95%)achieved by iridium-192 endoradiotherapy of accessible T1, T2, T3, and T4 cancers."} {"id": "PMID:183541", "title": "Subtotal mastectomy and radiation therapy in the definitive management of localized breast malignancy.", "content": "Between 1961 and 1974, 51 women with primary carcinoma of the breast were treated by external radiation following surgery that was limited to diagnostic biopsy. All patients tolerated therapy well with minimal long term morbidity. While the reported follow-up periods are brief (most patients at risk for less than 3 years), 29 patients remain alive, 25 of whom show no evidence of persistent or recurring disease. These data suggest that local-regional control rates match those obtained following mastectomy. Definitive statements as to local failures and long term survival rates are not yet available.", "contents": "Subtotal mastectomy and radiation therapy in the definitive management of localized breast malignancy. Between 1961 and 1974, 51 women with primary carcinoma of the breast were treated by external radiation following surgery that was limited to diagnostic biopsy. All patients tolerated therapy well with minimal long term morbidity. While the reported follow-up periods are brief (most patients at risk for less than 3 years), 29 patients remain alive, 25 of whom show no evidence of persistent or recurring disease. These data suggest that local-regional control rates match those obtained following mastectomy. Definitive statements as to local failures and long term survival rates are not yet available."} {"id": "PMID:183542", "title": "Postoperative irradiation in the prevention of keloids.", "content": "Low dose superficial x-irradiation to the incisional site after surgical excision of a keloid prevented keloid or hypertrophic scar formation in 31 of 35 patients evaluated (88%). The clinical manifestation of keloids, physiology of wound healing, pathophysiology of keloid formation, and the radiation technique utilized are presented. This study shows that the method is well tolerated, easily administered, and efficient in inhibiting recurrence of keloid or hypertrophic scar formation.", "contents": "Postoperative irradiation in the prevention of keloids. Low dose superficial x-irradiation to the incisional site after surgical excision of a keloid prevented keloid or hypertrophic scar formation in 31 of 35 patients evaluated (88%). The clinical manifestation of keloids, physiology of wound healing, pathophysiology of keloid formation, and the radiation technique utilized are presented. This study shows that the method is well tolerated, easily administered, and efficient in inhibiting recurrence of keloid or hypertrophic scar formation."} {"id": "PMID:183543", "title": "Parametrial calcification in cervical carcinoma patients treated with radioactive gold.", "content": "A unique appearance of soft tissue calcification in the pelvis which may be specific for patients treated with parametrial injection of 198Au colloid is described. The calcification appears in the area of maximum radiation dose and can appear within 5 years of treatment. It is significant because it occurred in approximately one-half of the cases radiographically reviewed and may be confused with calcification from other etiologies.", "contents": "Parametrial calcification in cervical carcinoma patients treated with radioactive gold. A unique appearance of soft tissue calcification in the pelvis which may be specific for patients treated with parametrial injection of 198Au colloid is described. The calcification appears in the area of maximum radiation dose and can appear within 5 years of treatment. It is significant because it occurred in approximately one-half of the cases radiographically reviewed and may be confused with calcification from other etiologies."} {"id": "PMID:183544", "title": "Nodular lymphoid hyperplasia of the colon associated with dysgammaglobulinemia.", "content": "A case of dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the colon is reported. The patient had typical immunoglobulin deficiency, diarrhea, recurrent respiratory infections, Giardia lamblia in the stool, and lymphoid hyperplasia of the small intestine. His barium enema showed diffuse submucosal nodules. Rectosigmoid biopsy confirmed nodular lymphoid hyperplasia. The similar findings on barium enema in this entity and in lymphosarcoma are stressed.", "contents": "Nodular lymphoid hyperplasia of the colon associated with dysgammaglobulinemia. A case of dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the colon is reported. The patient had typical immunoglobulin deficiency, diarrhea, recurrent respiratory infections, Giardia lamblia in the stool, and lymphoid hyperplasia of the small intestine. His barium enema showed diffuse submucosal nodules. Rectosigmoid biopsy confirmed nodular lymphoid hyperplasia. The similar findings on barium enema in this entity and in lymphosarcoma are stressed."} {"id": "PMID:183545", "title": "Massive enlargement of the ileocecal valve due to lymphoid hyperplasia.", "content": "Two children with unusual infiltration of the ileocecal valve by lymphoid tissue are described. The large filling defect identified on barium enema may suggest a number of conditions. Operative resection will exclude the possibility of a malignant process and will reduce the chance of recurrent intussusception.", "contents": "Massive enlargement of the ileocecal valve due to lymphoid hyperplasia. Two children with unusual infiltration of the ileocecal valve by lymphoid tissue are described. The large filling defect identified on barium enema may suggest a number of conditions. Operative resection will exclude the possibility of a malignant process and will reduce the chance of recurrent intussusception."} {"id": "PMID:183548", "title": "Unilateral dysplasia of the superior articular facet of the axis.", "content": "A case of unilateral dysplasia of the superior articular facet of the axis due to incomplete or delayed ossification is described in a child. This may result in asymmetry of the articular surfaces of the axis in adult life and be a cause of torticollis. To our knowledge, no similar case has been reported.", "contents": "Unilateral dysplasia of the superior articular facet of the axis. A case of unilateral dysplasia of the superior articular facet of the axis due to incomplete or delayed ossification is described in a child. This may result in asymmetry of the articular surfaces of the axis in adult life and be a cause of torticollis. To our knowledge, no similar case has been reported."} {"id": "PMID:183549", "title": "Arteriographic findings in hyperergic granulomatosis and vasculitis of a kidney.", "content": "A case with a probable diagnosis of a limited form of Wegener's granulomatosis is presented. Arteriography of an involved kidney revealed arterial occlusions and stenoses with infarcted parenchymal regions and a distinct collateral circulation. Compared to the renal changes in other collagenous diseases, the renovasographic findings in this case were more prominent, more centrally located, and of segmental distribution.", "contents": "Arteriographic findings in hyperergic granulomatosis and vasculitis of a kidney. A case with a probable diagnosis of a limited form of Wegener's granulomatosis is presented. Arteriography of an involved kidney revealed arterial occlusions and stenoses with infarcted parenchymal regions and a distinct collateral circulation. Compared to the renal changes in other collagenous diseases, the renovasographic findings in this case were more prominent, more centrally located, and of segmental distribution."} {"id": "PMID:183550", "title": "Interim report: mammographic exposures at the breast cancer detection demonstration project screening centers.", "content": "In the interests of uniformly high radiological physics standards at ACS-NCI Breast Cancer Detection Demonstration Projects, measurements were made at 29 breast cancer screening clinics. These measurements were made throughout the country with equipment calibrated with standards traceable to National Bureau of Standards. Histograms which indicate the frequency distribution of exposures to the surface of a 6 cm breast for various machine/receptor combinations were prepared.", "contents": "Interim report: mammographic exposures at the breast cancer detection demonstration project screening centers. In the interests of uniformly high radiological physics standards at ACS-NCI Breast Cancer Detection Demonstration Projects, measurements were made at 29 breast cancer screening clinics. These measurements were made throughout the country with equipment calibrated with standards traceable to National Bureau of Standards. Histograms which indicate the frequency distribution of exposures to the surface of a 6 cm breast for various machine/receptor combinations were prepared."} {"id": "PMID:183554", "title": "Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers.", "content": "One hundred and fifteen persons with asymptomatic Entamoeba histolytica or E. hartmanni infection, or both, were given metronidazole (750 mg three times daily for 5 days), tinidazole (1 g twice daily on 2 consecutive days), or a starch placebo. Three post-treatment stools were examined in the 2 weeks following initiation of treatment. Cysts of E. histolytica reappeared in the stools of 37% of 30 given metronidazole, 62% of 34 given tinidazole, and 70% of 31 given placebo. Cysts of E. hartmanni reappeared in the stools of 46% of 24 given metronidazole, 69% of 16 given tinidazole, and 90% of 10 given placebo. Rapid absorption and short duration of treatment make both drugs ineffective for the treatment of ameba carriers.", "contents": "Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers. One hundred and fifteen persons with asymptomatic Entamoeba histolytica or E. hartmanni infection, or both, were given metronidazole (750 mg three times daily for 5 days), tinidazole (1 g twice daily on 2 consecutive days), or a starch placebo. Three post-treatment stools were examined in the 2 weeks following initiation of treatment. Cysts of E. histolytica reappeared in the stools of 37% of 30 given metronidazole, 62% of 34 given tinidazole, and 70% of 31 given placebo. Cysts of E. hartmanni reappeared in the stools of 46% of 24 given metronidazole, 69% of 16 given tinidazole, and 90% of 10 given placebo. Rapid absorption and short duration of treatment make both drugs ineffective for the treatment of ameba carriers."} {"id": "PMID:183555", "title": "Seroepidemiology of amebiasis in the Orang Asli (Western Malaysian aborigine) and other Malaysians.", "content": "The indirect hemagglutination test was used to study antibody titers to Entamoeba histolytica in different Malaysian populations. Eighty-seven percent of Orang Asli (western Malaysian aborigines) adults and 79% of Orang Asli children with acute amebic dysentery were seropositive. However, significantly fewer children (39%) with amebic dysentery had high titer responses (titer greater than or equal to 1:1,280) than did adults with amebic dysentery (76%). No correlation between proctoscopic severity and amebic titer was found. Forty-four percent of asymptomatic family members were seroresponders. Satak, an Orang Asli village located near towns, had significantly more seroresponders (32%) than did the isolated, deep jungle village, Belatim (4%).", "contents": "Seroepidemiology of amebiasis in the Orang Asli (Western Malaysian aborigine) and other Malaysians. The indirect hemagglutination test was used to study antibody titers to Entamoeba histolytica in different Malaysian populations. Eighty-seven percent of Orang Asli (western Malaysian aborigines) adults and 79% of Orang Asli children with acute amebic dysentery were seropositive. However, significantly fewer children (39%) with amebic dysentery had high titer responses (titer greater than or equal to 1:1,280) than did adults with amebic dysentery (76%). No correlation between proctoscopic severity and amebic titer was found. Forty-four percent of asymptomatic family members were seroresponders. Satak, an Orang Asli village located near towns, had significantly more seroresponders (32%) than did the isolated, deep jungle village, Belatim (4%)."} {"id": "PMID:183556", "title": "Persistence of virus-specific IgM and clinical recovery after Japanese encephalitis.", "content": "We have searched for evidence of a chronic Japanese encephalitis virus (JEV) infection in six Thai patients convalescing from acute Japanese encephalitis (JE) in whom JEV-specific IgM antibody was last detected 116 to 350 days after their acute illness. These six patients were compared with 94 other JE patients matched for age, sex and serological response and in whom JEV-specific IgM was either short-lived (less than 90 days) or not tested. All patients were evaluated for the presence or absence of seven abnormal neurological signs over a 1- to 2-year period. During the first 30 days of illness the mean numbers (+/- S.E.M.) of abnormal signs per patients for the IgM and control groups were 3.8 +/- 0.3 and 2.3 +/- 0.1, respectively (P less than 0.01). After 1 year the six IgM patients still had significantly more abnormal neurological signs than controls (1.3 +/- 0.3 and 0.6 +/- 0.1, respectively [P less than 0.01]). By 2 years, the IgM group showed no neurological impairment; examination of cerebrospinal fluids revealed no evidence of subclinical viral infections. The recovery of the six IgM patients between 1 and 2 years after their relatively severe acute illness suggests that IgM antibody persistence was related to acute virulence rather than chronicity of the JEV infection.", "contents": "Persistence of virus-specific IgM and clinical recovery after Japanese encephalitis. We have searched for evidence of a chronic Japanese encephalitis virus (JEV) infection in six Thai patients convalescing from acute Japanese encephalitis (JE) in whom JEV-specific IgM antibody was last detected 116 to 350 days after their acute illness. These six patients were compared with 94 other JE patients matched for age, sex and serological response and in whom JEV-specific IgM was either short-lived (less than 90 days) or not tested. All patients were evaluated for the presence or absence of seven abnormal neurological signs over a 1- to 2-year period. During the first 30 days of illness the mean numbers (+/- S.E.M.) of abnormal signs per patients for the IgM and control groups were 3.8 +/- 0.3 and 2.3 +/- 0.1, respectively (P less than 0.01). After 1 year the six IgM patients still had significantly more abnormal neurological signs than controls (1.3 +/- 0.3 and 0.6 +/- 0.1, respectively [P less than 0.01]). By 2 years, the IgM group showed no neurological impairment; examination of cerebrospinal fluids revealed no evidence of subclinical viral infections. The recovery of the six IgM patients between 1 and 2 years after their relatively severe acute illness suggests that IgM antibody persistence was related to acute virulence rather than chronicity of the JEV infection."} {"id": "PMID:183560", "title": "[Acupuncture and pain mechanisms (author's transl)].", "content": "Three modulating mechanisms of the \"gate-control theory\" provide a plausible explanation of how acupuncture analgesia works. In particular, the inhibitory effects of the brainstem reticular formation on the transmission of pain signals in the spinal cord or at higher ttransmission levels seems to provide a powerful explanatory concept. Intense stimulation through acupuncture needles could activate this inhibitory brainstem system, thereby closing the gate to pain signals.", "contents": "[Acupuncture and pain mechanisms (author's transl)]. Three modulating mechanisms of the \"gate-control theory\" provide a plausible explanation of how acupuncture analgesia works. In particular, the inhibitory effects of the brainstem reticular formation on the transmission of pain signals in the spinal cord or at higher ttransmission levels seems to provide a powerful explanatory concept. Intense stimulation through acupuncture needles could activate this inhibitory brainstem system, thereby closing the gate to pain signals."} {"id": "PMID:183572", "title": "Leukocyte cyclic-3', 5'-nucleotide phosphodiesterase activity in human bronchial asthma.", "content": "Changes in cyclic-3', 5'-nucleotide phosphodiesterase activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Leukocyte phosphodiesterase activity was significantly elevated during asthmatic attacks. Elevated activity was seen in most active asthmatics irrespective of the drug treatment. The ratio of the adenyl cyclase activity to the phosphodiesterase activity of the same leukocyte decreased to less than 1.0 during asthmatic attacks.", "contents": "Leukocyte cyclic-3', 5'-nucleotide phosphodiesterase activity in human bronchial asthma. Changes in cyclic-3', 5'-nucleotide phosphodiesterase activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Leukocyte phosphodiesterase activity was significantly elevated during asthmatic attacks. Elevated activity was seen in most active asthmatics irrespective of the drug treatment. The ratio of the adenyl cyclase activity to the phosphodiesterase activity of the same leukocyte decreased to less than 1.0 during asthmatic attacks."} {"id": "PMID:183573", "title": "Neutralization of a transmissible gastroenteritis virus of swine by colostral antibodies elicited by intestine and cell culture-propagated virus.", "content": "Cross-protection studies of gilts exposed to 4 transmissible gastroenteritis viruses--Ilinois (field strain), Miller-3, Miller low passage (M-LP), and Miller high passage (M-HP) tissue culture-adapted--indicated that only the gilt vaccinated with Illinois strain was protected, along with its newborn pigs, against challenge exposure with field virus. Similar results were obtained when the 4 viruses were incubated in vitro with colostrum from each of the 4 vaccinated gilts and subsequently used to orally inoculate newborn pigs. However, when the colostrums were used to neutralize M-HP virus in cell cultures, the neutralization titers were similar, indicating that a close antigenic relationship existed among the viruses. Neutralization studies in cell cultures, using immunoglobulin (Ig) fractions derived from colostrums of sows exposed to Illinois and M-HP virus, indicated that Illinois virus elicited more neutralizing activity in IgA than in the IgG fraction and that M-HP virus elicited more IgG than IgA antibody activity. In another study, Illinois virus was treated with these Ig-enriched fractions and then inoculated into the lumen of the jejunum of 3-day-old pigs. Anti-Illinois IgA was the only class of antibody which prevented replication of the Illinois virus in the intestine. Similar intraintestinal inoculations were used to test invasiveness of untreated Illinois and M-HP viruses. It was demonstrated that Illinois virus caused marked effect on the intestine: shortening of the villi, intestinal distension, edema, and presence of accumulated intestinal fluid within 60 hours after inoculation. The M-HP virus grew in the intestinal cells without affecting the length of the villi. The degree of invasiveness of Illinois or M-HP virus may account for the difference in the antibody class elicited in the colostrums.", "contents": "Neutralization of a transmissible gastroenteritis virus of swine by colostral antibodies elicited by intestine and cell culture-propagated virus. Cross-protection studies of gilts exposed to 4 transmissible gastroenteritis viruses--Ilinois (field strain), Miller-3, Miller low passage (M-LP), and Miller high passage (M-HP) tissue culture-adapted--indicated that only the gilt vaccinated with Illinois strain was protected, along with its newborn pigs, against challenge exposure with field virus. Similar results were obtained when the 4 viruses were incubated in vitro with colostrum from each of the 4 vaccinated gilts and subsequently used to orally inoculate newborn pigs. However, when the colostrums were used to neutralize M-HP virus in cell cultures, the neutralization titers were similar, indicating that a close antigenic relationship existed among the viruses. Neutralization studies in cell cultures, using immunoglobulin (Ig) fractions derived from colostrums of sows exposed to Illinois and M-HP virus, indicated that Illinois virus elicited more neutralizing activity in IgA than in the IgG fraction and that M-HP virus elicited more IgG than IgA antibody activity. In another study, Illinois virus was treated with these Ig-enriched fractions and then inoculated into the lumen of the jejunum of 3-day-old pigs. Anti-Illinois IgA was the only class of antibody which prevented replication of the Illinois virus in the intestine. Similar intraintestinal inoculations were used to test invasiveness of untreated Illinois and M-HP viruses. It was demonstrated that Illinois virus caused marked effect on the intestine: shortening of the villi, intestinal distension, edema, and presence of accumulated intestinal fluid within 60 hours after inoculation. The M-HP virus grew in the intestinal cells without affecting the length of the villi. The degree of invasiveness of Illinois or M-HP virus may account for the difference in the antibody class elicited in the colostrums."} {"id": "PMID:183574", "title": "Apparent propagation of the equine infectious anemia virus in a mosquito (Culex pipiens quinquefasciatus Say) ovarian cell line.", "content": "A tissue culture of Culex pipiens quinquefasciatus Say ovarian cells appeared to support the growth of equine infectious anemia (EIA) virus. Shetland ponies inoculated with 2nd, 7th, 9th, and 11th passages of mediums harvested from infected tissue culture had clinical signs of the disease and became EIA positive on 11, 19, 23, and 43 days after inoculation, respectively.", "contents": "Apparent propagation of the equine infectious anemia virus in a mosquito (Culex pipiens quinquefasciatus Say) ovarian cell line. A tissue culture of Culex pipiens quinquefasciatus Say ovarian cells appeared to support the growth of equine infectious anemia (EIA) virus. Shetland ponies inoculated with 2nd, 7th, 9th, and 11th passages of mediums harvested from infected tissue culture had clinical signs of the disease and became EIA positive on 11, 19, 23, and 43 days after inoculation, respectively."} {"id": "PMID:183575", "title": "Development of a cell culture line of bovine fetal endometrial cells.", "content": "Monolayers of bovine fetal endometrial cells were established as primary culture cells within 1 to 2 weeks. After the 2nd passage, these cells were inoculated with bovine viral diarrhea virus. Effects of the virus were observed each day with a light microscope. Specific cytopathic effects consisting of degeneration and sloughing of the cells and a well-defined pattern of cytoplasmic vacuolation were observed at 5 days after inoculation.", "contents": "Development of a cell culture line of bovine fetal endometrial cells. Monolayers of bovine fetal endometrial cells were established as primary culture cells within 1 to 2 weeks. After the 2nd passage, these cells were inoculated with bovine viral diarrhea virus. Effects of the virus were observed each day with a light microscope. Specific cytopathic effects consisting of degeneration and sloughing of the cells and a well-defined pattern of cytoplasmic vacuolation were observed at 5 days after inoculation."} {"id": "PMID:183576", "title": "Cholestyramine: an effective, twice-daily dosage regimen.", "content": "Nine patients with familial hypercholesterolemia (type II hyperlipoproteinemia) and two normal volunteers were studied to ascertain the effectiveness of cholestyramine in lowering plasma cholesterol when a twice-a-day dosage regimen was compared with the same total dosage administered four times a day. The study showed that in these subjects the two regimens were equally effective. The ability to administer cholestyramine twice daily in working adults and school children should greatly enhance adherence to this agent.", "contents": "Cholestyramine: an effective, twice-daily dosage regimen. Nine patients with familial hypercholesterolemia (type II hyperlipoproteinemia) and two normal volunteers were studied to ascertain the effectiveness of cholestyramine in lowering plasma cholesterol when a twice-a-day dosage regimen was compared with the same total dosage administered four times a day. The study showed that in these subjects the two regimens were equally effective. The ability to administer cholestyramine twice daily in working adults and school children should greatly enhance adherence to this agent."} {"id": "PMID:183577", "title": "Adriamycin and enhanced radiation reaction in normal esophagus and skin.", "content": "Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions was notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin.", "contents": "Adriamycin and enhanced radiation reaction in normal esophagus and skin. Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions was notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin."} {"id": "PMID:183578", "title": "Defective lung macrophages in pulmonary alveolar proteinosis.", "content": "Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment.", "contents": "Defective lung macrophages in pulmonary alveolar proteinosis. Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment."} {"id": "PMID:183579", "title": "Vitamin D endocrinology.", "content": "Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed.", "contents": "Vitamin D endocrinology. Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed."} {"id": "PMID:183580", "title": "[Sex hormones in the male].", "content": "The measurement of androgen hormones in reduced times using small samples of blood is nowadays possible by using the radioimmunological techniques. The level of testosterone in plasma is directly correlated with glandular secretion, though several different factors may provoke variations of such level. The measurement of testosterone in plasma is used for evaluation of testicular function. The main applications of testosterone determination in clinical practice are reported; special stress is laid on diagnosis on male hypogonadisms and on the study of testicular function in male sexual impotence.", "contents": "[Sex hormones in the male]. The measurement of androgen hormones in reduced times using small samples of blood is nowadays possible by using the radioimmunological techniques. The level of testosterone in plasma is directly correlated with glandular secretion, though several different factors may provoke variations of such level. The measurement of testosterone in plasma is used for evaluation of testicular function. The main applications of testosterone determination in clinical practice are reported; special stress is laid on diagnosis on male hypogonadisms and on the study of testicular function in male sexual impotence."} {"id": "PMID:183581", "title": "[Evaluation and standardization of radioimmunoassays].", "content": "The term \"standardization\" may be applied to RIA methods to indicate the \"definition of quality characteristics\" the level of which must be defined on the basis of the evaluation of the \"analytical procedure/specific reagents\" system. Each laboratory, by applying a suitable long-term quality control system, must assure the consistent maintenance of the \"standardization status\" established for all mehtods it uses. As a matter of fact, in the case of RIA, materials are used that have a limited stability, that cannot be produced in large quantities, and that possess a complex composition not always well defined chemically. However, a remarkable role in the standardization process belongs to the producers of special reagents intended for RIA. In order to help the standardization of RIA methods, some programs of inter-laborator cooperation have been worked out in recent years. Among them mention is specifically made of three studies regarding the dosage of insulin: the most recent of them is devised and coordinated by the Instituto Superiore di Santi\u00e0 in cooperation with the Laboratory of Clinical Physiology of the National Research Council of Pisa. The availability of standardized materials is estremely important: for antigens, some materials are already in existence, but it is desirable that the various manufacturers shall follow more uniform criteria in their standardization. As far as the application of the RIA methods in the diagnostic field is concerned, the need exists for the use of standardized basic schemes that would include and unambiguously express all the useful information available in order to define better the clinical significance of the analytical data obtained.", "contents": "[Evaluation and standardization of radioimmunoassays]. The term \"standardization\" may be applied to RIA methods to indicate the \"definition of quality characteristics\" the level of which must be defined on the basis of the evaluation of the \"analytical procedure/specific reagents\" system. Each laboratory, by applying a suitable long-term quality control system, must assure the consistent maintenance of the \"standardization status\" established for all mehtods it uses. As a matter of fact, in the case of RIA, materials are used that have a limited stability, that cannot be produced in large quantities, and that possess a complex composition not always well defined chemically. However, a remarkable role in the standardization process belongs to the producers of special reagents intended for RIA. In order to help the standardization of RIA methods, some programs of inter-laborator cooperation have been worked out in recent years. Among them mention is specifically made of three studies regarding the dosage of insulin: the most recent of them is devised and coordinated by the Instituto Superiore di Santi\u00e0 in cooperation with the Laboratory of Clinical Physiology of the National Research Council of Pisa. The availability of standardized materials is estremely important: for antigens, some materials are already in existence, but it is desirable that the various manufacturers shall follow more uniform criteria in their standardization. As far as the application of the RIA methods in the diagnostic field is concerned, the need exists for the use of standardized basic schemes that would include and unambiguously express all the useful information available in order to define better the clinical significance of the analytical data obtained."} {"id": "PMID:183586", "title": "Characteristics and mechanism of neuromuscular block in myasthenia gravis.", "content": "The neuromuscular block of myasthenia gravis has the characteristics of an antidepolarizing (competitive block), similar to that produced by d-tubocurarine in normal subjects: progressive decrease in muscle action potentials evoked by two or more nerve stimuli, posttetanic facilitation, posttetanic fatigue, inhibition of the depolarizing action of acetylcholine (ACh) or anticholinesterase compounds, and reversal of the block by ACh or anticholinesterase compounds. In myasthenic patients spontaneously recurring negative discharges were more difficult to locate in the end-plate zone than in normal subjects, suggesting that the number or density of functioning end plates may be reduced. The threshold dose of intra-arterial ACh that increased electrical activity was higher than in normal subjects; the duration of the increased electrical activity was briefer, and was followed by more depression of negative discharges than in normal subjects and by a greater increase in the threshold dose of ACh. These results indicate that the end-plate zone of myasthenic patients is less responsive than that of normal subjects to the excitatory action of ACh, and may be more readily desensitized by ACh. In both myasthenic patients and normal subjects the intra-arterial injection of ACh produced a prompt transient decrease in evoked potentials, attributable to depolarization of the end plates, followed by recovery (and in myasthenic patients by repair), and then by a more prolonged late decrease in evoked potentials, attributable to desensitization of the end plates to transmitter. This prompt depressant effect of ACh on evoked potentials was less in myasthenic patients than in normal subjects, and the late depressant effect of ACh was greater. In myasthenic patients the late block produced by ACh had the characteristics of an antidepolarizing (competitive) type of block, including inhibition of the depolarizing action of ACh and reversibility by ACh or neostigmine, while in normal subjects the characteristics were those of a depolarizing (noncompetitive) type of block, including little or no inhibition of the depolarizing action of ACh and lack of reversal by ACh or neostigmine. The differences between the late depressant action of ACh in myasthenic patients and normal subjects resembled differences in the effect of other depolarizing compounds, such as choline, succinylcholine, and decamethonium, and are best explained by differences in behavior of the postsynaptic receptor. The disease appears to be due to the presence of abnormal forms of receptor or to abnormal responses of receptor to the transmitter. The predominance of one or other form of receptor may determine the clinical state of the myasthenic patient and his response to anticholinesterase medication.", "contents": "Characteristics and mechanism of neuromuscular block in myasthenia gravis. The neuromuscular block of myasthenia gravis has the characteristics of an antidepolarizing (competitive block), similar to that produced by d-tubocurarine in normal subjects: progressive decrease in muscle action potentials evoked by two or more nerve stimuli, posttetanic facilitation, posttetanic fatigue, inhibition of the depolarizing action of acetylcholine (ACh) or anticholinesterase compounds, and reversal of the block by ACh or anticholinesterase compounds. In myasthenic patients spontaneously recurring negative discharges were more difficult to locate in the end-plate zone than in normal subjects, suggesting that the number or density of functioning end plates may be reduced. The threshold dose of intra-arterial ACh that increased electrical activity was higher than in normal subjects; the duration of the increased electrical activity was briefer, and was followed by more depression of negative discharges than in normal subjects and by a greater increase in the threshold dose of ACh. These results indicate that the end-plate zone of myasthenic patients is less responsive than that of normal subjects to the excitatory action of ACh, and may be more readily desensitized by ACh. In both myasthenic patients and normal subjects the intra-arterial injection of ACh produced a prompt transient decrease in evoked potentials, attributable to depolarization of the end plates, followed by recovery (and in myasthenic patients by repair), and then by a more prolonged late decrease in evoked potentials, attributable to desensitization of the end plates to transmitter. This prompt depressant effect of ACh on evoked potentials was less in myasthenic patients than in normal subjects, and the late depressant effect of ACh was greater. In myasthenic patients the late block produced by ACh had the characteristics of an antidepolarizing (competitive) type of block, including inhibition of the depolarizing action of ACh and reversibility by ACh or neostigmine, while in normal subjects the characteristics were those of a depolarizing (noncompetitive) type of block, including little or no inhibition of the depolarizing action of ACh and lack of reversal by ACh or neostigmine. The differences between the late depressant action of ACh in myasthenic patients and normal subjects resembled differences in the effect of other depolarizing compounds, such as choline, succinylcholine, and decamethonium, and are best explained by differences in behavior of the postsynaptic receptor. The disease appears to be due to the presence of abnormal forms of receptor or to abnormal responses of receptor to the transmitter. The predominance of one or other form of receptor may determine the clinical state of the myasthenic patient and his response to anticholinesterase medication."} {"id": "PMID:183584", "title": "Effect of benomyl and thiophanate-methyl on metabolic activities of Rhizoctonia solani K\u00fchn.", "content": "Effect of benomyl and thiophanate-methyl on various metabolic activities of Rhizoctonia solani was investigated. Both fungitoxicants strongly reduced endogenous whole cell and mitochondrial respiration by inhibiting one or the other key enzymes of electron transport chain; the activity of cytochrome oxidase being most markedly inhibited. Incorporation of 3II-thymidine was reduced by both while there was little or no inhibition in the rate of incorporation of 14C-uracil and 14C-leucine. Cell permeability was not affected to any appreciable extent and there was a little release of cellular components from the treated cells only at prolonged incubation. It is concluded that benomyl and thiophanate-methyl have a similar mode of action which primarily involves inhibition of respiratory activities, and as a consequence the biosynthesis of DNA is reduced.", "contents": "Effect of benomyl and thiophanate-methyl on metabolic activities of Rhizoctonia solani K\u00fchn. Effect of benomyl and thiophanate-methyl on various metabolic activities of Rhizoctonia solani was investigated. Both fungitoxicants strongly reduced endogenous whole cell and mitochondrial respiration by inhibiting one or the other key enzymes of electron transport chain; the activity of cytochrome oxidase being most markedly inhibited. Incorporation of 3II-thymidine was reduced by both while there was little or no inhibition in the rate of incorporation of 14C-uracil and 14C-leucine. Cell permeability was not affected to any appreciable extent and there was a little release of cellular components from the treated cells only at prolonged incubation. It is concluded that benomyl and thiophanate-methyl have a similar mode of action which primarily involves inhibition of respiratory activities, and as a consequence the biosynthesis of DNA is reduced."} {"id": "PMID:183590", "title": "Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management.", "content": "The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.", "contents": "Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management. The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit."} {"id": "PMID:183591", "title": "Alternate-day prednisone: preliminary report of a double-blind controlled study.", "content": "Thirteen patients with moderately severe myasthenia gravis participated in a double-blind study using either 100 mg of prednisone or an equivalen numbder of placebo tablets on alternate days. Anticholinesterase therapy was continued on a demand basis. At the end of 6 months the code was broken. Seven patients were on placebo and three of these had improved to such a degree that steroid therapy was not indicated. Four of these patients ultimately were started on prednisone and improved. Of the six patients on prednisone, three showed no improvement and three were improved. At the end of 2 years, the seven patients still taking prednisone were on maintenance dosage of this drug. Three of this group had experienced relapses when the dosage was cut to 15 to 25 mg on alternate days, and they again improved when the prednisone dosage was increased. No statistical evaluation is possible because of the small number of patients. It can be stated that seven patients improved with steroid therapy. Conversely, not all patients treated with alternate-day prednisone improved. Finally, any evaluation of treatment of myasthenia gravis must take into consideration the potential for spontaneous improvement, as demonstrated by three of the patients treated with placebo.", "contents": "Alternate-day prednisone: preliminary report of a double-blind controlled study. Thirteen patients with moderately severe myasthenia gravis participated in a double-blind study using either 100 mg of prednisone or an equivalen numbder of placebo tablets on alternate days. Anticholinesterase therapy was continued on a demand basis. At the end of 6 months the code was broken. Seven patients were on placebo and three of these had improved to such a degree that steroid therapy was not indicated. Four of these patients ultimately were started on prednisone and improved. Of the six patients on prednisone, three showed no improvement and three were improved. At the end of 2 years, the seven patients still taking prednisone were on maintenance dosage of this drug. Three of this group had experienced relapses when the dosage was cut to 15 to 25 mg on alternate days, and they again improved when the prednisone dosage was increased. No statistical evaluation is possible because of the small number of patients. It can be stated that seven patients improved with steroid therapy. Conversely, not all patients treated with alternate-day prednisone improved. Finally, any evaluation of treatment of myasthenia gravis must take into consideration the potential for spontaneous improvement, as demonstrated by three of the patients treated with placebo."} {"id": "PMID:183592", "title": "Effects of some immunosuppressive procedures on myasthenia gravis.", "content": "Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.", "contents": "Effects of some immunosuppressive procedures on myasthenia gravis. Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied."} {"id": "PMID:183594", "title": "The specificity and nature of serum-angiotensin-converting enzyme (serum ACE) elevations in sarcoidosis.", "content": "Elevation of serum-angiotensin-converting enzyme (serum ACE) in patients with active sarcoidosis was confirmed in a total of 64 subjects with a mean serum ACE of 15.76+/-7.4 units compared with 6.05+/-2.0 units in 194 patients with other types of respiratory disease. Resolution of the sarcoidosis disease state or therapeutic control with adequate doses of corticosteroids (15 mg prednisone daily) brought the elevated serum ACE levels down into the normal range. A longitudinal study of serum ACE activity was found to be an effective way of judging the therapeutic efficacy of various steroid dosage levels. No other disease state involved in the differential diagnosis of sarcoidosis was found to have elevations of serum ACE activity. However, 6 patients with Gaucher's disease did have elevated serum ACE activity that ranged well above the usual level seen even in patients with sarcoidosis. The two diseases could be readily distinguished in the laboratory by elevated serum acid phosphatase activity in most cases of Gaucher's disease. It would appear that detection of elevated serum ACE levels can be a useful procedure for confirming a diagnosis of active sarcoidosis and for judging the therapeutic response.", "contents": "The specificity and nature of serum-angiotensin-converting enzyme (serum ACE) elevations in sarcoidosis. Elevation of serum-angiotensin-converting enzyme (serum ACE) in patients with active sarcoidosis was confirmed in a total of 64 subjects with a mean serum ACE of 15.76+/-7.4 units compared with 6.05+/-2.0 units in 194 patients with other types of respiratory disease. Resolution of the sarcoidosis disease state or therapeutic control with adequate doses of corticosteroids (15 mg prednisone daily) brought the elevated serum ACE levels down into the normal range. A longitudinal study of serum ACE activity was found to be an effective way of judging the therapeutic efficacy of various steroid dosage levels. No other disease state involved in the differential diagnosis of sarcoidosis was found to have elevations of serum ACE activity. However, 6 patients with Gaucher's disease did have elevated serum ACE activity that ranged well above the usual level seen even in patients with sarcoidosis. The two diseases could be readily distinguished in the laboratory by elevated serum acid phosphatase activity in most cases of Gaucher's disease. It would appear that detection of elevated serum ACE levels can be a useful procedure for confirming a diagnosis of active sarcoidosis and for judging the therapeutic response."} {"id": "PMID:183595", "title": "Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance.", "content": "A statistically highly significant elevation of serum ACE was found in a group of 58 patients with sarcoidosis (serum ACE was elevated in 34% of patients), as compared with normal controls and patients with tuberculosis and various other common diseases. The results suggest that serum ACE is a useful aid for the diagnosis of sarcoidosis when elevated, but that a normal value does not rule out the condition and may occur in more than one-half of monitored patients. There is a trend to diminution of serum ACE with increasing duration of disease with or without steroid therapy, perhaps correlating with the total body mass of active granulomas, as indirectly suggested in preliminary data by correlation of serum ACE with serum globulin in 16 sarcoidosis patients. It is not yet clear whether there is any significant steroid effect on serum ACE, but a significant number of patients on steroid therapy for more than 2-4 yr have elevated serum ACE values, which in some instances are extremely high. There was a 12-fold elevation in ACE to specific activities generally exceeding those of normal lung in granulomatous lymph nodes of 14 patients with sarcoidosis, suggesting that sarcoid granulomas may be actively synthesizing ACE and resulting in elevation of serum ACE. Extensively fibrotic sarcoid lymph nodes had normal or slightly elevated ACE, suggesting that obliteration of granulomas in sarcoid lymph nodes diminishes their ACE content and that this obliteration may be related to the tendency to diminution of serum ACE with time. ACE was not elevated in one tuberculous lymph node or in experimental granulomas, suggesting that elevation of ACE may have some specificity for the granuloma of sarcoidosis rather than being a characteristic of all granulomas. The catalytic and physical properties of ACE in serum and lymph nodes in sarcoidosis were generally similar to normal ACE with respect to pH activity, modulators, polyacrylamide-gel electrophoresis, and Sephadex G-200 gel filtration. However, sarcoid lymph node ACE appeared to be more heat labile than normal lung or lymph node ACE, suggesting the possibility that an abnormal ACE may be present in sarcoidosis. If an abnormal enzyme is indeed present, it might be coded for by a host gene that is not normally expressed or a nonhost gene or it might be a normal ACE that has been altered. No ACE activity was found in circulating white blood cells in sarcoidosis or in control subjects, suggesting that circulating white blood cells may not contain the epithelioid cell precursor or that ACE synthesis (or less likely, uptake) may be turned on at a later stage in the transformation. Lysozyme activity was also elevated in sarcoid lymph nodes. Serum ACE and serum lysozyme were significantly positively correlated in 16 sarcoidosis patients, suggesting a relationship between the two...", "contents": "Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance. A statistically highly significant elevation of serum ACE was found in a group of 58 patients with sarcoidosis (serum ACE was elevated in 34% of patients), as compared with normal controls and patients with tuberculosis and various other common diseases. The results suggest that serum ACE is a useful aid for the diagnosis of sarcoidosis when elevated, but that a normal value does not rule out the condition and may occur in more than one-half of monitored patients. There is a trend to diminution of serum ACE with increasing duration of disease with or without steroid therapy, perhaps correlating with the total body mass of active granulomas, as indirectly suggested in preliminary data by correlation of serum ACE with serum globulin in 16 sarcoidosis patients. It is not yet clear whether there is any significant steroid effect on serum ACE, but a significant number of patients on steroid therapy for more than 2-4 yr have elevated serum ACE values, which in some instances are extremely high. There was a 12-fold elevation in ACE to specific activities generally exceeding those of normal lung in granulomatous lymph nodes of 14 patients with sarcoidosis, suggesting that sarcoid granulomas may be actively synthesizing ACE and resulting in elevation of serum ACE. Extensively fibrotic sarcoid lymph nodes had normal or slightly elevated ACE, suggesting that obliteration of granulomas in sarcoid lymph nodes diminishes their ACE content and that this obliteration may be related to the tendency to diminution of serum ACE with time. ACE was not elevated in one tuberculous lymph node or in experimental granulomas, suggesting that elevation of ACE may have some specificity for the granuloma of sarcoidosis rather than being a characteristic of all granulomas. The catalytic and physical properties of ACE in serum and lymph nodes in sarcoidosis were generally similar to normal ACE with respect to pH activity, modulators, polyacrylamide-gel electrophoresis, and Sephadex G-200 gel filtration. However, sarcoid lymph node ACE appeared to be more heat labile than normal lung or lymph node ACE, suggesting the possibility that an abnormal ACE may be present in sarcoidosis. If an abnormal enzyme is indeed present, it might be coded for by a host gene that is not normally expressed or a nonhost gene or it might be a normal ACE that has been altered. No ACE activity was found in circulating white blood cells in sarcoidosis or in control subjects, suggesting that circulating white blood cells may not contain the epithelioid cell precursor or that ACE synthesis (or less likely, uptake) may be turned on at a later stage in the transformation. Lysozyme activity was also elevated in sarcoid lymph nodes. Serum ACE and serum lysozyme were significantly positively correlated in 16 sarcoidosis patients, suggesting a relationship between the two..."} {"id": "PMID:183596", "title": "Estimation of T- and K-cell activity in the peripheral blood of sarcoidosis patients.", "content": "Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment.", "contents": "Estimation of T- and K-cell activity in the peripheral blood of sarcoidosis patients. Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment."} {"id": "PMID:183598", "title": "Isozymes of glyceraldehyde-3-phosphate dehydrogenase in man and other mammals.", "content": "Multiple electrophoretically distinct forms of glyceraldehyde-3-phosphate dehydrogenase have been observed in human and other mammalian tissues. The human isozymes appear to have essentially the same structural and kinetic properties. An apparent correlation between red-cell age and the relative intensities of the isozymes supports the idea that the isozymes arise as a result of post-translational modification of the polypeptide chain. The possibility that a second locus is involved in the determination of these isozymes is discussed.", "contents": "Isozymes of glyceraldehyde-3-phosphate dehydrogenase in man and other mammals. Multiple electrophoretically distinct forms of glyceraldehyde-3-phosphate dehydrogenase have been observed in human and other mammalian tissues. The human isozymes appear to have essentially the same structural and kinetic properties. An apparent correlation between red-cell age and the relative intensities of the isozymes supports the idea that the isozymes arise as a result of post-translational modification of the polypeptide chain. The possibility that a second locus is involved in the determination of these isozymes is discussed."} {"id": "PMID:183599", "title": "The control of glycogen metabolism in the liver.", "content": "The major factor that controls glycogen metabolism in the liver is the concentration of phorphorylase alpha. Indeed, this enzyme catalyzes the limiting step of glycogen breakdown and, by controlling the activity of synthetase phosphatase, also regulates glycogen synthesis. The formation of phosphorylase alpha is stimulated by cAMP, by glycogen, and presumably also by some still ill-defined ionic changes. The ininactivation of phosphorylase is greatly stimulated by glucose and inhibited by AMP and glycogen. Glycogen synthesis is proportional to the concentration of synthetase alpha, which in normally fed animals is formed only when most of the phosphorylase is in the beta form. The inactivation of glycogen synthetase is stimulated by cAMP, an elevated concentration of which puts a double lock on glycogen synthetase by activating phosphorylase alpha (and thereby preventing synthetase activation) and by inactivating glycogen synthetase. The effect of cAMP, 5'-AMP, glucose, and glycogen can presently be explained in molecular terms. The main missing link is in the ionic effect whose elucidation might lead to the understanding of the mode of action of insulin.", "contents": "The control of glycogen metabolism in the liver. The major factor that controls glycogen metabolism in the liver is the concentration of phorphorylase alpha. Indeed, this enzyme catalyzes the limiting step of glycogen breakdown and, by controlling the activity of synthetase phosphatase, also regulates glycogen synthesis. The formation of phosphorylase alpha is stimulated by cAMP, by glycogen, and presumably also by some still ill-defined ionic changes. The ininactivation of phosphorylase is greatly stimulated by glucose and inhibited by AMP and glycogen. Glycogen synthesis is proportional to the concentration of synthetase alpha, which in normally fed animals is formed only when most of the phosphorylase is in the beta form. The inactivation of glycogen synthetase is stimulated by cAMP, an elevated concentration of which puts a double lock on glycogen synthetase by activating phosphorylase alpha (and thereby preventing synthetase activation) and by inactivating glycogen synthetase. The effect of cAMP, 5'-AMP, glucose, and glycogen can presently be explained in molecular terms. The main missing link is in the ionic effect whose elucidation might lead to the understanding of the mode of action of insulin."} {"id": "PMID:183604", "title": "[Histochemistry and electron microscopy of the embryonal development of the golden hamster kidney: study of the interstitial cells].", "content": "The structure and the origin of the interstitial cells in the kidney of the golden Hamster during its embryonic development was studied. For this purpose kidneys from 11, 13, 15 and 17 day-old embryos were used. The histochemical observations as well as the electron microscopy demonstrated that the interstitial cells have a metanephric origin and are embryonically similar to the cellular elements that differentiate the primordial renal vesicles and later organise the epithelial portion of the nephrons. These cells seem to take part in the formation of the basal membranes during tubular genesis.", "contents": "[Histochemistry and electron microscopy of the embryonal development of the golden hamster kidney: study of the interstitial cells]. The structure and the origin of the interstitial cells in the kidney of the golden Hamster during its embryonic development was studied. For this purpose kidneys from 11, 13, 15 and 17 day-old embryos were used. The histochemical observations as well as the electron microscopy demonstrated that the interstitial cells have a metanephric origin and are embryonically similar to the cellular elements that differentiate the primordial renal vesicles and later organise the epithelial portion of the nephrons. These cells seem to take part in the formation of the basal membranes during tubular genesis."} {"id": "PMID:183605", "title": "BCG immunoprophylaxis of recurrent herpes progenitalis.", "content": "Thirty-eight patients with severe, recurrent herpes progenitalis were treated by immunoprophylaxis with repeated BCG inoculations. Results of the study demonstrated no significant prophylactic benefit of BCG when contrasted to other homologous or heterologous antigens or to control patients receiving placebos. Caution is warranted in the use of homologous vaccines from Germany because theoretically, tumor growth might be enhanced by immunologic means, although the vaccine apparently has no intrinsic oncogenic qualities.", "contents": "BCG immunoprophylaxis of recurrent herpes progenitalis. Thirty-eight patients with severe, recurrent herpes progenitalis were treated by immunoprophylaxis with repeated BCG inoculations. Results of the study demonstrated no significant prophylactic benefit of BCG when contrasted to other homologous or heterologous antigens or to control patients receiving placebos. Caution is warranted in the use of homologous vaccines from Germany because theoretically, tumor growth might be enhanced by immunologic means, although the vaccine apparently has no intrinsic oncogenic qualities."} {"id": "PMID:183606", "title": "Angiokeratoma corporis diffusum (Fabry disease). A lysosomal disease.", "content": "Angiokeratoma corporis diffusum (Fabry disease) is an X-linked recessive disease. We had an opportunity to examine a heterozygous female patient with angiokeratoma and cornea verticillata. The patient's serum alpha-galactosidase activity was reported to be about 50% of normal. Skin lesion biopsy specimens were stained with electron microscopic acid phsophatase (ACP), with proper controls. Acid phosphatase activity was demonstrable within membrane-bound inclusions of cutaneous vascular endothelial cells. This suggested that the accumulation of abnormal glycolipids in the vascular cells occurs in the lysosomes.", "contents": "Angiokeratoma corporis diffusum (Fabry disease). A lysosomal disease. Angiokeratoma corporis diffusum (Fabry disease) is an X-linked recessive disease. We had an opportunity to examine a heterozygous female patient with angiokeratoma and cornea verticillata. The patient's serum alpha-galactosidase activity was reported to be about 50% of normal. Skin lesion biopsy specimens were stained with electron microscopic acid phsophatase (ACP), with proper controls. Acid phosphatase activity was demonstrable within membrane-bound inclusions of cutaneous vascular endothelial cells. This suggested that the accumulation of abnormal glycolipids in the vascular cells occurs in the lysosomes."} {"id": "PMID:183608", "title": "Nevus sebaceous and syringocystadenoma papilliferum.", "content": "A 52-year-old patient was admitted to the hosptial for evaluation of hypertension. He had two skin lesions, one on the forehead and one in the postauricular area, which had been present since birth. The forehead lesion was a nevus sebaceous and the postauricular lesion was a syringocystadenoma papilliferum. Except for a few patients with widespread nevus sebaceous and syringocystadenoma papilliferum associated with neurologic abnormalities, most of the previously reported patients with these nevi have had solitary lesions of one or the other. An association of nevus sebaceous and syringocystadenoma papilliferum in the same lesion is not uncommon. Despite bleeding and crusting in one of the lesions and despite informing the patient that a malignant neoplasm may develop in these nevi, he refused excision of either of the lesions.", "contents": "Nevus sebaceous and syringocystadenoma papilliferum. A 52-year-old patient was admitted to the hosptial for evaluation of hypertension. He had two skin lesions, one on the forehead and one in the postauricular area, which had been present since birth. The forehead lesion was a nevus sebaceous and the postauricular lesion was a syringocystadenoma papilliferum. Except for a few patients with widespread nevus sebaceous and syringocystadenoma papilliferum associated with neurologic abnormalities, most of the previously reported patients with these nevi have had solitary lesions of one or the other. An association of nevus sebaceous and syringocystadenoma papilliferum in the same lesion is not uncommon. Despite bleeding and crusting in one of the lesions and despite informing the patient that a malignant neoplasm may develop in these nevi, he refused excision of either of the lesions."} {"id": "PMID:183609", "title": "Idiopathic hypoglycaemia in sibs with morphological evidence of nesidioblastosis of the pancreas.", "content": "Two sibs who sustained severe hypoglycaemia in the neonatal period are reported. In spite of treatment with frequent feeds intravenous glucose, glucagon, hydrocortisone, and diazoxide, hypoglycaemia persisted, and both infants eventually required subtotal pancreatectomy. Tests for leucine toleranct were normal though the second case showed some protein sensitivity. Histological and immunohistochemical studies indicated nesidioblastosis in both specimens of pancreata. The children are presently performing at mildly retarded levels, and required diazoxide and anticonvulsant medication for some time postoperatively. Because both sexes are represetned, an autosomal recessive inheritance pattern is suggested. The theory of a gut hormone stimulating insulin production is briefly discussed.", "contents": "Idiopathic hypoglycaemia in sibs with morphological evidence of nesidioblastosis of the pancreas. Two sibs who sustained severe hypoglycaemia in the neonatal period are reported. In spite of treatment with frequent feeds intravenous glucose, glucagon, hydrocortisone, and diazoxide, hypoglycaemia persisted, and both infants eventually required subtotal pancreatectomy. Tests for leucine toleranct were normal though the second case showed some protein sensitivity. Histological and immunohistochemical studies indicated nesidioblastosis in both specimens of pancreata. The children are presently performing at mildly retarded levels, and required diazoxide and anticonvulsant medication for some time postoperatively. Because both sexes are represetned, an autosomal recessive inheritance pattern is suggested. The theory of a gut hormone stimulating insulin production is briefly discussed."} {"id": "PMID:183610", "title": "Response in the newborn to raised upper airway resistance.", "content": "The effect of raising the airways resistance of 56 normal newborn babies by blocking alternate nostrils was studied by means of oesophageal intubation and the trunk plethysmograph. Increased resistance was associated with reduced respiratory rate and ventilation. A comparison was made of the response in different sleep states. In rapid eye movement (REM) sleep respiratory tidal volume decreased on blocking, there was no increase in the work of breathing and the fall in minute volume was greater than in non-REM sleep where tidal volume and minute work increased on blocking. These responses may be relevant to the sudden unexpected death syndrome in infancy, and to the management of normal newborns.", "contents": "Response in the newborn to raised upper airway resistance. The effect of raising the airways resistance of 56 normal newborn babies by blocking alternate nostrils was studied by means of oesophageal intubation and the trunk plethysmograph. Increased resistance was associated with reduced respiratory rate and ventilation. A comparison was made of the response in different sleep states. In rapid eye movement (REM) sleep respiratory tidal volume decreased on blocking, there was no increase in the work of breathing and the fall in minute volume was greater than in non-REM sleep where tidal volume and minute work increased on blocking. These responses may be relevant to the sudden unexpected death syndrome in infancy, and to the management of normal newborns."} {"id": "PMID:183611", "title": "Langerhans cells at the sites of vaccinia virus inoculation.", "content": "Langerhans cells in the epidermis at the sites of vaccina virus inoculation were studied with the electron microscope. The cells contained unusually increased numbers of the Langerhans cell granules. Such abnormal Langerhans cells have not been described except for in histiocytosis X. Vaccinia virus particles were found in the Langerhans cells, where they were located individually or embedded in the granular matrix or in lysosomes.", "contents": "Langerhans cells at the sites of vaccinia virus inoculation. Langerhans cells in the epidermis at the sites of vaccina virus inoculation were studied with the electron microscope. The cells contained unusually increased numbers of the Langerhans cell granules. Such abnormal Langerhans cells have not been described except for in histiocytosis X. Vaccinia virus particles were found in the Langerhans cells, where they were located individually or embedded in the granular matrix or in lysosomes."} {"id": "PMID:183612", "title": "On the occurrence of sphaeridia in basalioma cells and the basal cells of the overlying epidermis.", "content": "302 nuclear sections of basalioma cells, 145 nuclear sections of the basal cells of the epidermis above the tumor, and 177 nuclear sections of the basal cells of normal epidermis were investigated and statistically evaluated with the aim of determining the presence of sphaeridia occur significantly more frequently in the basal cells of the epidermis above the tumor and in normal epidermis than in the tumor itself. These findings are discussed in connection with the degree of cellular protein synthesis.", "contents": "On the occurrence of sphaeridia in basalioma cells and the basal cells of the overlying epidermis. 302 nuclear sections of basalioma cells, 145 nuclear sections of the basal cells of the epidermis above the tumor, and 177 nuclear sections of the basal cells of normal epidermis were investigated and statistically evaluated with the aim of determining the presence of sphaeridia occur significantly more frequently in the basal cells of the epidermis above the tumor and in normal epidermis than in the tumor itself. These findings are discussed in connection with the degree of cellular protein synthesis."} {"id": "PMID:183613", "title": "[Quantitative histometric investigations on the epidermis and corium of rat paw after experimental inflammation (author's transl)].", "content": "The epidermis and corium of rat right hind paw were investigated both histologically and histometrically after a subplantar injection of aerosil, formalin, carrageenin or Freund's complete adjuvant. The thickness of the epidermis and corium was determined on 5 rats respectively at 12 different times between 0.5 and 480 h post-treatment. Paw swelling was measured plethysmometrically on living rats. The left paw of untreated rats as well as the saline-injected and the untreated left paw of carrageenin-treated and adjuvant-treated animals respectively served as controls. Results 1. After the injection of the 4 substances, an acute inflammation developed maximally 4 to 24 h post-treatment in the corium. The thickness of the corium increased simultaneously with paw swelling. 2. Epidermal hyperplasia set in after a lag-phase of 12 h following the injection of formalin, carrageenin and adjuvant. 3. After injection of aerosil a subcutaneous oedema developed but no epidermal hyperplasia occured. 4. The formation of granulation tissue and necroses in the corium was seen only in the adjuvant-treated group 4 to 20 days post-treatment. At the same time, epidermal hyperplasia reached an absolute maximum. 5. The disturbance of nutrition and the lack of oxygen in the inflamed corium is possibly responsible for the initiation and persistence of the hyperplasia.", "contents": "[Quantitative histometric investigations on the epidermis and corium of rat paw after experimental inflammation (author's transl)]. The epidermis and corium of rat right hind paw were investigated both histologically and histometrically after a subplantar injection of aerosil, formalin, carrageenin or Freund's complete adjuvant. The thickness of the epidermis and corium was determined on 5 rats respectively at 12 different times between 0.5 and 480 h post-treatment. Paw swelling was measured plethysmometrically on living rats. The left paw of untreated rats as well as the saline-injected and the untreated left paw of carrageenin-treated and adjuvant-treated animals respectively served as controls. Results 1. After the injection of the 4 substances, an acute inflammation developed maximally 4 to 24 h post-treatment in the corium. The thickness of the corium increased simultaneously with paw swelling. 2. Epidermal hyperplasia set in after a lag-phase of 12 h following the injection of formalin, carrageenin and adjuvant. 3. After injection of aerosil a subcutaneous oedema developed but no epidermal hyperplasia occured. 4. The formation of granulation tissue and necroses in the corium was seen only in the adjuvant-treated group 4 to 20 days post-treatment. At the same time, epidermal hyperplasia reached an absolute maximum. 5. The disturbance of nutrition and the lack of oxygen in the inflamed corium is possibly responsible for the initiation and persistence of the hyperplasia."} {"id": "PMID:183614", "title": "Actions and interactions of theophylline and imidazole on cardiac contractility, phosphorylase activation and cyclic AMP.", "content": "Injection of 1.0 mg theophylline and 1.6 mg imidazole into guinea-pig hearts perfused by the Langendorff technique increased cardiac contractile force by 20.0 +/- 1.0% and 23.3 +/- 1.2% over control and activated phosphorylase without producing significant changes in cyclic AMP levels. When guinea-pig hearts were perfused with theophylline (10(-3) M) or imidazole (20 mM), injection of either imidazole or theophylline did not further increase cardiac contractility or phosphorylase a levels. In all cases there was no change in cycylic AMP levels. Data in the literature indicate that calcium plays a role in the cardiac biochemical and mechanical effects of theophylline and imidazole. Both drugs may thus produce their cardiac effects by a calcium rather than a cyclic AMP mediated mechanism.", "contents": "Actions and interactions of theophylline and imidazole on cardiac contractility, phosphorylase activation and cyclic AMP. Injection of 1.0 mg theophylline and 1.6 mg imidazole into guinea-pig hearts perfused by the Langendorff technique increased cardiac contractile force by 20.0 +/- 1.0% and 23.3 +/- 1.2% over control and activated phosphorylase without producing significant changes in cyclic AMP levels. When guinea-pig hearts were perfused with theophylline (10(-3) M) or imidazole (20 mM), injection of either imidazole or theophylline did not further increase cardiac contractility or phosphorylase a levels. In all cases there was no change in cycylic AMP levels. Data in the literature indicate that calcium plays a role in the cardiac biochemical and mechanical effects of theophylline and imidazole. Both drugs may thus produce their cardiac effects by a calcium rather than a cyclic AMP mediated mechanism."} {"id": "PMID:183615", "title": "Bile duct carcinoma mimicking chronic liver disease.", "content": "In a case of cholangiocarcinoma involving the bifurcation of the common duct, the association with striking intermittence of jaundice and with signs of chronic liver disease presented a diagnostic enigma. Disappearance of jaundice does not rule out the diagnosis of bifurcation tumors and may be misleading. Adequate demonstration of the biliary tree, best achieved with percutaneous transhepatic cholangiography, is essential for early diagnosis of this entity.", "contents": "Bile duct carcinoma mimicking chronic liver disease. In a case of cholangiocarcinoma involving the bifurcation of the common duct, the association with striking intermittence of jaundice and with signs of chronic liver disease presented a diagnostic enigma. Disappearance of jaundice does not rule out the diagnosis of bifurcation tumors and may be misleading. Adequate demonstration of the biliary tree, best achieved with percutaneous transhepatic cholangiography, is essential for early diagnosis of this entity."} {"id": "PMID:183616", "title": "Ribulose 1,5-diphosphate carboxylase and Cholorobium thiosulfatophilum.", "content": "1. Cell-free extracts of the photosynthetic bacterium Cholorobium thiosulfatophilum, strains 8327 and Tassajara, were assayed for ribulose 1,5-diphosphate (RuDP) carboxylase and phosphoribulokinase--the two enzymes peculiar to the reductive pentose phosphate cycle. 2. RuDP carboxylase was consistently absent in strain 8327. The Tassajara strain showed a low RuDP-dependent CO2 fixation activity that was somewhat higher in cells following transatlantic air shipment than in freshly grown cells. The stability and behaviour of this activity in sucrose density gradients were similar to those described by other workers. 3. The radioactive carboxylation products formed in the presence of RuDP by enzyme preparations from the Tassajara strain did not include 3-phosphoglycerate--the known product of the RuDP carboxylase reaction, but instead consisted of the unrelated acids glutamate, aspartate and malate. 4. Phosphoribulokinase was absent in all preparations of the two Chlorobium strains tested. By contrast, phosphoribulokinase as well as RuDP carboxylase were readily demonstrated in preparations from pea chloroplasts and the photosynthetic bacterium Rhodospirillum rubrum. 5. It is concluded that C. thiosulfatophilum appears to lack RuDP carboxylase, phosphoribulokinase, and hence, the reductive pentose phosphate cycle.", "contents": "Ribulose 1,5-diphosphate carboxylase and Cholorobium thiosulfatophilum. 1. Cell-free extracts of the photosynthetic bacterium Cholorobium thiosulfatophilum, strains 8327 and Tassajara, were assayed for ribulose 1,5-diphosphate (RuDP) carboxylase and phosphoribulokinase--the two enzymes peculiar to the reductive pentose phosphate cycle. 2. RuDP carboxylase was consistently absent in strain 8327. The Tassajara strain showed a low RuDP-dependent CO2 fixation activity that was somewhat higher in cells following transatlantic air shipment than in freshly grown cells. The stability and behaviour of this activity in sucrose density gradients were similar to those described by other workers. 3. The radioactive carboxylation products formed in the presence of RuDP by enzyme preparations from the Tassajara strain did not include 3-phosphoglycerate--the known product of the RuDP carboxylase reaction, but instead consisted of the unrelated acids glutamate, aspartate and malate. 4. Phosphoribulokinase was absent in all preparations of the two Chlorobium strains tested. By contrast, phosphoribulokinase as well as RuDP carboxylase were readily demonstrated in preparations from pea chloroplasts and the photosynthetic bacterium Rhodospirillum rubrum. 5. It is concluded that C. thiosulfatophilum appears to lack RuDP carboxylase, phosphoribulokinase, and hence, the reductive pentose phosphate cycle."} {"id": "PMID:183617", "title": "Action of polymyxin B on bacterial membranes. Binding capacities for polymyxin B of inner and outer membranes isolated from Salmonella typhimurium G30.", "content": "Radioactive mono-N-acetyl-14C-polymyxin B or natural polymyxin B are within 60 s absorbed by isolated inner (cytoplasmic) and outer membranes from Salmonella typhimuriumG30. The sigmoidal binding isotherms indicate saturation of inner and outer membranes with approximately 30 and 60 nmoles polymyxin B bound per mg membrane, respectively. Based on the known content of these membranes in lipopolysaccharide, phosphatidylglycerol, cardiolipin and phosphatidylethanolamine, a calculation of the theoretical binding capacities yields almost identical values if lipopolysaccharide, phosphatidylglycerol and cardiolipin are assumed to function as the actual binding sites for the antibiotic in the isolated membranes. The excellent agreement between theoretical evaluation and experimental determination of polymyxin B-binding capacities leaves little doubt that the named anionic compounds are the chemoreceptors for the cationic antibiotic. This is further substantiated by very similar binding and killing kinetics of polymyxin B.", "contents": "Action of polymyxin B on bacterial membranes. Binding capacities for polymyxin B of inner and outer membranes isolated from Salmonella typhimurium G30. Radioactive mono-N-acetyl-14C-polymyxin B or natural polymyxin B are within 60 s absorbed by isolated inner (cytoplasmic) and outer membranes from Salmonella typhimuriumG30. The sigmoidal binding isotherms indicate saturation of inner and outer membranes with approximately 30 and 60 nmoles polymyxin B bound per mg membrane, respectively. Based on the known content of these membranes in lipopolysaccharide, phosphatidylglycerol, cardiolipin and phosphatidylethanolamine, a calculation of the theoretical binding capacities yields almost identical values if lipopolysaccharide, phosphatidylglycerol and cardiolipin are assumed to function as the actual binding sites for the antibiotic in the isolated membranes. The excellent agreement between theoretical evaluation and experimental determination of polymyxin B-binding capacities leaves little doubt that the named anionic compounds are the chemoreceptors for the cationic antibiotic. This is further substantiated by very similar binding and killing kinetics of polymyxin B."} {"id": "PMID:183618", "title": "[DNA synthesis in spinal ganglia of rabbit after Herpes suis infection. Findings obtained by electron microscopy and autoradiography].", "content": "The mulitplication of herpes suis virus in neurons, amphicytes, gliocytes, as well as Schwann's and endothelial cells of the spinal ganglion of rabbit was traced by electron microscopy and autoradiography, using tritium-labelled thymidine. Marking of nuclear zone margin, quite common when it comes to ganglion cells, was observed also in the context of mesenchymal cells beyond expectation on the basis of light microscopy, but in the case under review it had no direct relationship with virus synthesis. Repeated markings were recorded from the nucleoli of apparently unchanged ganglion cells which suggested the suitability of the technique for early detection of infectious attack on intact cells. Exogenous 3H-thymidine was supplied three hours and absorbed with specificity by the DNA-forming centres of the nuclei, but the growing virus drew into itself additional cellular or inactive thymidine. The method proved to be highly significant, as in comparison to the nuclear environment there were ten times as many lemnici in the DNA production centres of neurons and Schwann's cells and about six times as many in the amphicytes and gliocytes. Now, there is definite justification in rejecting as unfounded all doubt expressed repeatedly and more recently in the specificity of herpes-dependent intranuclear inclusions.", "contents": "[DNA synthesis in spinal ganglia of rabbit after Herpes suis infection. Findings obtained by electron microscopy and autoradiography]. The mulitplication of herpes suis virus in neurons, amphicytes, gliocytes, as well as Schwann's and endothelial cells of the spinal ganglion of rabbit was traced by electron microscopy and autoradiography, using tritium-labelled thymidine. Marking of nuclear zone margin, quite common when it comes to ganglion cells, was observed also in the context of mesenchymal cells beyond expectation on the basis of light microscopy, but in the case under review it had no direct relationship with virus synthesis. Repeated markings were recorded from the nucleoli of apparently unchanged ganglion cells which suggested the suitability of the technique for early detection of infectious attack on intact cells. Exogenous 3H-thymidine was supplied three hours and absorbed with specificity by the DNA-forming centres of the nuclei, but the growing virus drew into itself additional cellular or inactive thymidine. The method proved to be highly significant, as in comparison to the nuclear environment there were ten times as many lemnici in the DNA production centres of neurons and Schwann's cells and about six times as many in the amphicytes and gliocytes. Now, there is definite justification in rejecting as unfounded all doubt expressed repeatedly and more recently in the specificity of herpes-dependent intranuclear inclusions."} {"id": "PMID:183619", "title": "[Superneutralization test--a new virus serology examination procedure].", "content": "The serum neutralisation test, based on the antigen-antibody reaction and cytopathic action of a given virus upon certain in-vitro cultured cell systems, was expanded to the dimensions of a super-neutralisation test by including specific control sera with known titre and applying then to all samples positive to serum neutralisation through repeated addition of virus to tubular cell cultures with no CPE in the serum neutralisation test. Another antigen-antibody reaction was introduced by repeated addition of virus. In samples with less antibody (lower titre) due to lacking or partial neutralisation of added virus such reaction gave a CPE of with the intensity was inversely proportional to the titre. The CPE (cytopathic effect) will disappear beyond a certain titre limit owing to complete neutralisation of added virus. The point of disappearance can be controlled to the purpose of the given test by appropriate choice of the virus dose. This approach will entail negligible extra expenses but enable, in addition to qualitative assessment of reagents, quantitative identification of their antibody titres, and this will, no doubt, add to the informative weight of the test result. The advent of the super-neutralisation test has added to laboratory diagnosis in the field of virus serology a conventiently applicable, uninvolved, and highly effective technique.", "contents": "[Superneutralization test--a new virus serology examination procedure]. The serum neutralisation test, based on the antigen-antibody reaction and cytopathic action of a given virus upon certain in-vitro cultured cell systems, was expanded to the dimensions of a super-neutralisation test by including specific control sera with known titre and applying then to all samples positive to serum neutralisation through repeated addition of virus to tubular cell cultures with no CPE in the serum neutralisation test. Another antigen-antibody reaction was introduced by repeated addition of virus. In samples with less antibody (lower titre) due to lacking or partial neutralisation of added virus such reaction gave a CPE of with the intensity was inversely proportional to the titre. The CPE (cytopathic effect) will disappear beyond a certain titre limit owing to complete neutralisation of added virus. The point of disappearance can be controlled to the purpose of the given test by appropriate choice of the virus dose. This approach will entail negligible extra expenses but enable, in addition to qualitative assessment of reagents, quantitative identification of their antibody titres, and this will, no doubt, add to the informative weight of the test result. The advent of the super-neutralisation test has added to laboratory diagnosis in the field of virus serology a conventiently applicable, uninvolved, and highly effective technique."} {"id": "PMID:183620", "title": "[General adaptation syndrome (Selye) in the calf. 5. Effect of increased glucocorticosteroid values on the phagocytosis activity of luekocytes, the function of RHS and the morphology of lymphatic organs].", "content": "Studies were conducted with the view to elucidating the correlations between increased glucocorticosteroid levels in the blood and the defense potential of calf organism against infectious diseases. The test animals were exposed to several substances (ACTH, cortisol, colibacteria, coliendotoxin), and even one to two days of increased 11-OHKS values were followed by marked decline in phagocytosis activity of leucocytes. In addition, RHS function was considerably reduced, after ten to thirteen days of application had elapsed, since at that point the disappearance of intravenously applied bacteria from circulating blood of test animals took place at rates which were much lower than those recorded from untreated calves. Differentiated length of stress or action (four to thirteen days) was followed by conspicuous changes in the lymphatic tissue of calf organism, with severe involution of thymus and follicular atrophy of intestine-associated lymphatic tissue having been the major findings. The results seem to suggest that rise in adrenocortical hormone level under stress may reduce potential organic defense to infection.", "contents": "[General adaptation syndrome (Selye) in the calf. 5. Effect of increased glucocorticosteroid values on the phagocytosis activity of luekocytes, the function of RHS and the morphology of lymphatic organs]. Studies were conducted with the view to elucidating the correlations between increased glucocorticosteroid levels in the blood and the defense potential of calf organism against infectious diseases. The test animals were exposed to several substances (ACTH, cortisol, colibacteria, coliendotoxin), and even one to two days of increased 11-OHKS values were followed by marked decline in phagocytosis activity of leucocytes. In addition, RHS function was considerably reduced, after ten to thirteen days of application had elapsed, since at that point the disappearance of intravenously applied bacteria from circulating blood of test animals took place at rates which were much lower than those recorded from untreated calves. Differentiated length of stress or action (four to thirteen days) was followed by conspicuous changes in the lymphatic tissue of calf organism, with severe involution of thymus and follicular atrophy of intestine-associated lymphatic tissue having been the major findings. The results seem to suggest that rise in adrenocortical hormone level under stress may reduce potential organic defense to infection."} {"id": "PMID:183622", "title": "Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes.", "content": "The electroencephalographic sleep patterns of 12 patients with a final diagnosis of primary depression and those of 12 patients admitted to the Clinical Research Unit with this diagnosis, but subsequently also found to be suffering from severe medical disease, were compared. Patients with depression concurrent with severe medical disease have significantly less phasic conjugate rapid eye movement (REM) activity during REM sleep than subjects with the diagnosis of a primary depression. These findings suggest that quantification of REM density may be used clinically to distinguish between medical-depressive syndromes and primary affective disorders.", "contents": "Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes. The electroencephalographic sleep patterns of 12 patients with a final diagnosis of primary depression and those of 12 patients admitted to the Clinical Research Unit with this diagnosis, but subsequently also found to be suffering from severe medical disease, were compared. Patients with depression concurrent with severe medical disease have significantly less phasic conjugate rapid eye movement (REM) activity during REM sleep than subjects with the diagnosis of a primary depression. These findings suggest that quantification of REM density may be used clinically to distinguish between medical-depressive syndromes and primary affective disorders."} {"id": "PMID:183623", "title": "Electroencephalographic sleep diagnosis of primary depression.", "content": "Studies of severely depressed hospitalized patients suggest a shortened rapid eye movement (REM) latency as a specific biological marker for primary affective disease. To assess the validity of these findings, 40 outpatients referred to our Electroencephalographic Sleep Center for evaluation of depressive symptoms were studied. Concurrent with the all night EEG sleep studies, all patients received a brief clinical interview and a battery of self-rating scales. The entire sample was then subdivided into primary and secondary depressives on the basis of follow-up diagnoses. While there were no significant differences between groups on self-ratings of depressive symptoms, the group of primary depressives had significantly shorter REM latencies and higher measures of phasic REM than the secondary depressives. Furthermore, in this patient group, the delineation of primary vs secondary depression was greater than 80% on the basis of only two nights of EEG sleep. Such objective biological measures, if replicated, could provide a method for increasing the accuracy of differential diagnosis among depressed populations in clinical research.", "contents": "Electroencephalographic sleep diagnosis of primary depression. Studies of severely depressed hospitalized patients suggest a shortened rapid eye movement (REM) latency as a specific biological marker for primary affective disease. To assess the validity of these findings, 40 outpatients referred to our Electroencephalographic Sleep Center for evaluation of depressive symptoms were studied. Concurrent with the all night EEG sleep studies, all patients received a brief clinical interview and a battery of self-rating scales. The entire sample was then subdivided into primary and secondary depressives on the basis of follow-up diagnoses. While there were no significant differences between groups on self-ratings of depressive symptoms, the group of primary depressives had significantly shorter REM latencies and higher measures of phasic REM than the secondary depressives. Furthermore, in this patient group, the delineation of primary vs secondary depression was greater than 80% on the basis of only two nights of EEG sleep. Such objective biological measures, if replicated, could provide a method for increasing the accuracy of differential diagnosis among depressed populations in clinical research."} {"id": "PMID:183624", "title": "Poorly differentiated synovial sarcoma. A light and electron microscopic study.", "content": "Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation.", "contents": "Poorly differentiated synovial sarcoma. A light and electron microscopic study. Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation."} {"id": "PMID:183625", "title": "Nasal polyposis with stromal atypia. Review of follow-up study of 14 cases.", "content": "The clinical, microscopical, and gross pathological features of 14 cases of intranasal and paranasal sinus polyposis with unusual stromal cell atypia are described. In gross appearance, the lesions were polypoid, translucent masses, similar to the usual nasal polyp. Although clinically the lesions were indicative of allergic and inflammatory nasal polyposis, microscopical examination showed numerous large, often pleomorphic histiocytes or facultative fibroblasts that were suggestive or sarcomatous, malignant degeneration. Diagnoses by the original contributing pathologists included embryonal rhabdomyosarcoma, stromal neoplasia, and juvenile masopharyngeal angiofibroma. Follow-up data showed no evidence of neoplasia, despite the remarkable cytological changes found in the stroma. The stromal atypia most likely represents a reactive phenomenon secondary to inflammation.", "contents": "Nasal polyposis with stromal atypia. Review of follow-up study of 14 cases. The clinical, microscopical, and gross pathological features of 14 cases of intranasal and paranasal sinus polyposis with unusual stromal cell atypia are described. In gross appearance, the lesions were polypoid, translucent masses, similar to the usual nasal polyp. Although clinically the lesions were indicative of allergic and inflammatory nasal polyposis, microscopical examination showed numerous large, often pleomorphic histiocytes or facultative fibroblasts that were suggestive or sarcomatous, malignant degeneration. Diagnoses by the original contributing pathologists included embryonal rhabdomyosarcoma, stromal neoplasia, and juvenile masopharyngeal angiofibroma. Follow-up data showed no evidence of neoplasia, despite the remarkable cytological changes found in the stroma. The stromal atypia most likely represents a reactive phenomenon secondary to inflammation."} {"id": "PMID:183626", "title": "[The neuronal Torres bodies in experimental yellow fever encephalomyelitis. An additional example of the heterogeneous nature of Cowdry type A intranuclear inclusions].", "content": "In experimental yellow fever virus encephalomyelitis of adult albino mice, the occurrence of intranuclear inclusions within nerve cells, in particular, within spinal and bulbar motoneurons, is a constant finding. The light microscopic features of these so-called neuronal Torres bodies correspond entirely to the criteria laid down by Cowdry for the type A intranuclear inclusions. At the ultrastructural level, these karyoplasmic formations consist of haphazardly distributed patches of an essentially amorphous material of various density. Unlike the Cowdry type A intranuclear inclusions characteristic of several herpesvirus and paramyxovirus infections, neuronal Torr-s bodies do not contain any viral structures. The frequency with which neuronal Torres bodies, certain nucleolar alterations and severe tigrolytic changes occur together, possibly indicates that this sort of type A intranuclear inclusion developes as a consequence of a virus induced disturbance of the cell nucleic acid and/or protein anabolism.", "contents": "[The neuronal Torres bodies in experimental yellow fever encephalomyelitis. An additional example of the heterogeneous nature of Cowdry type A intranuclear inclusions]. In experimental yellow fever virus encephalomyelitis of adult albino mice, the occurrence of intranuclear inclusions within nerve cells, in particular, within spinal and bulbar motoneurons, is a constant finding. The light microscopic features of these so-called neuronal Torres bodies correspond entirely to the criteria laid down by Cowdry for the type A intranuclear inclusions. At the ultrastructural level, these karyoplasmic formations consist of haphazardly distributed patches of an essentially amorphous material of various density. Unlike the Cowdry type A intranuclear inclusions characteristic of several herpesvirus and paramyxovirus infections, neuronal Torr-s bodies do not contain any viral structures. The frequency with which neuronal Torres bodies, certain nucleolar alterations and severe tigrolytic changes occur together, possibly indicates that this sort of type A intranuclear inclusion developes as a consequence of a virus induced disturbance of the cell nucleic acid and/or protein anabolism."} {"id": "PMID:183628", "title": "Purification and characterization of equine infectious anemia virus.", "content": "EIA virus was purified from equine fetal kidney cell cultures by PEG-precipitation, two sucrose-gradient sedimentations (5-30 per cent) and (25 to 60 per cent) centrifugation, using the immunodiffusion test to follow the procedure. Purified EIA virus had a density (20 degrees C) of 1.162 and a sedimentation constant of S20w=656. electron microscopy revealed a particle of about 100 nm in diameter with a very flexible but usually spherical shape. The dense core may be at various locations inside the membrane bound particle.", "contents": "Purification and characterization of equine infectious anemia virus. EIA virus was purified from equine fetal kidney cell cultures by PEG-precipitation, two sucrose-gradient sedimentations (5-30 per cent) and (25 to 60 per cent) centrifugation, using the immunodiffusion test to follow the procedure. Purified EIA virus had a density (20 degrees C) of 1.162 and a sedimentation constant of S20w=656. electron microscopy revealed a particle of about 100 nm in diameter with a very flexible but usually spherical shape. The dense core may be at various locations inside the membrane bound particle."} {"id": "PMID:183629", "title": "The effect of influenza virus infection on the agglutinability by concanavalin A of polyoma-transformed BHK-21 cells.", "content": "Polyoma-transformed (Py-transformed) BHK-21 cells are agglutinated more readily by Concanavalin A (Con A) after they are infected with influenza virus; this agglutination was only slightly affected by fixation with glutaraldehyde or colchicine treatment. It is suggest that the mechanism is not dependent on membrane fluidity. The same amounts of 125i-labelled Con A were bound after infection with influenza virus and after glutaraldehyde fixation with or without colchicine treatment: it seems therefore that new receptors for Con A are not expressed between 90 and 600 minutes after these cells are infected with influenza virus.", "contents": "The effect of influenza virus infection on the agglutinability by concanavalin A of polyoma-transformed BHK-21 cells. Polyoma-transformed (Py-transformed) BHK-21 cells are agglutinated more readily by Concanavalin A (Con A) after they are infected with influenza virus; this agglutination was only slightly affected by fixation with glutaraldehyde or colchicine treatment. It is suggest that the mechanism is not dependent on membrane fluidity. The same amounts of 125i-labelled Con A were bound after infection with influenza virus and after glutaraldehyde fixation with or without colchicine treatment: it seems therefore that new receptors for Con A are not expressed between 90 and 600 minutes after these cells are infected with influenza virus."} {"id": "PMID:183630", "title": "Envelopment and the envelopes of infectious bovine rhinotracheitis virus in ultrathin sections.", "content": "An electron microsopic study of cell cultures and bovine foetal tracheal organ cultures infected with infectious bovine rhinotracheitis (IBR) virus showed the following. a) The difference in the site at which the outer envelope is acquired in the infected cell is responsible for some morphological differences between the virions. Where envelopment of the capsids occurs by budding into cytoplasmic tubules, dense material adjacent to the tubules is often incorporated between the capsid and the outer envelope, giving a pleomorphic appearance to the latter. No dense material is seen in the same position if envelopment occurs in the nucleus. b) Dense material adjacent to the cytoplasmic tubules is not only incorporated in the virions, but may also bud into the cytoplasmic tubules without nucleocapsids, thus giving rise to dense bodies. c) Dense material in the virions is closely adjacent to the inner side of the outer envelope, but is separated from the capsid by a lucent zone. A similar zone can be seen around some nucleocapsids in the nucleus. d) The outer envelope of numerous extracellular virions and of those located in the cytoplasmic tubules shows the unit membrane structure with projections. The outer envelope of intranuclear particles and of those located in the perinuclear cisterna had the appearance of a dense membrane.", "contents": "Envelopment and the envelopes of infectious bovine rhinotracheitis virus in ultrathin sections. An electron microsopic study of cell cultures and bovine foetal tracheal organ cultures infected with infectious bovine rhinotracheitis (IBR) virus showed the following. a) The difference in the site at which the outer envelope is acquired in the infected cell is responsible for some morphological differences between the virions. Where envelopment of the capsids occurs by budding into cytoplasmic tubules, dense material adjacent to the tubules is often incorporated between the capsid and the outer envelope, giving a pleomorphic appearance to the latter. No dense material is seen in the same position if envelopment occurs in the nucleus. b) Dense material adjacent to the cytoplasmic tubules is not only incorporated in the virions, but may also bud into the cytoplasmic tubules without nucleocapsids, thus giving rise to dense bodies. c) Dense material in the virions is closely adjacent to the inner side of the outer envelope, but is separated from the capsid by a lucent zone. A similar zone can be seen around some nucleocapsids in the nucleus. d) The outer envelope of numerous extracellular virions and of those located in the cytoplasmic tubules shows the unit membrane structure with projections. The outer envelope of intranuclear particles and of those located in the perinuclear cisterna had the appearance of a dense membrane."} {"id": "PMID:183632", "title": "Quantitative studies on adsorption, elution, and haemagglutination of vesicular stomatitis virus.", "content": "Radioactively-labelled VSV, both Indiana and New Jersey serotypes, were rapidly and efficiently adsorbed onto goose erythrocytes, but only within a narrow range of pH and at low temperatures. Under optimal conditions for adsorption, both infectivity and haemagglutinating activity of VSV were reduced. A basic difference between the two serotypes was identified: adsorption and haemagglutination of the Indiana serotype were stable even at pH 9.0 and at 37 degrees C, whereas New Jersey serotype was eluted slowly at +0 degrees C and at pH 6.4 and rapidly at a higher temperature and pH. The rapid elution offers a useful method for purification of New Jersey serotype. Particle counting of VSV showed that 10 to 50 virus particles were required for one PFU. Haemagglutination was not a sensitive method for assaying small amounts of VSV; 3--20X10(7) virus particles or more than 10(7) PFU corresponded to one HAU.", "contents": "Quantitative studies on adsorption, elution, and haemagglutination of vesicular stomatitis virus. Radioactively-labelled VSV, both Indiana and New Jersey serotypes, were rapidly and efficiently adsorbed onto goose erythrocytes, but only within a narrow range of pH and at low temperatures. Under optimal conditions for adsorption, both infectivity and haemagglutinating activity of VSV were reduced. A basic difference between the two serotypes was identified: adsorption and haemagglutination of the Indiana serotype were stable even at pH 9.0 and at 37 degrees C, whereas New Jersey serotype was eluted slowly at +0 degrees C and at pH 6.4 and rapidly at a higher temperature and pH. The rapid elution offers a useful method for purification of New Jersey serotype. Particle counting of VSV showed that 10 to 50 virus particles were required for one PFU. Haemagglutination was not a sensitive method for assaying small amounts of VSV; 3--20X10(7) virus particles or more than 10(7) PFU corresponded to one HAU."} {"id": "PMID:183633", "title": "[Herpesvirus-induced autoantibodies in animals (author's transl)].", "content": "After immunization with autologous testicle cells which were infected with herpes virus hominis type 1 or 2, histologically homogeneous, eosinophilie PAS-positive substances could be detected in five out of six rabbits, mainly within the interstitium. These substances have been found by immunofluorescence microscopic techniques to be antibodies against testicle tissue.", "contents": "[Herpesvirus-induced autoantibodies in animals (author's transl)]. After immunization with autologous testicle cells which were infected with herpes virus hominis type 1 or 2, histologically homogeneous, eosinophilie PAS-positive substances could be detected in five out of six rabbits, mainly within the interstitium. These substances have been found by immunofluorescence microscopic techniques to be antibodies against testicle tissue."} {"id": "PMID:183634", "title": "Ultrastructure of mouse periventricular and choroid plexus tissues in experimental vesicular stomatitis virus infection.", "content": "The ultrastructure of the periventricular and choroid plexus tissues was studied in the three-week-old mouse, infected with the vesicular stomatitis virus (VSV) by the intranasal route. The VSV reached the periventricular ependymal lining late in infection. It was carried within the cytoplasm of myelinated axons and their sheath cells. Inflammatory cells, although few in numbers, may have also contributed to the virus dissemination. Once in the periventricular tissues the VSV entered the cells from the intercellular space. It replicated in both the ependymal and subependymal cells. It matured either directly in the cytoplasm, or by budding from the plasmalemma as well as the cytoplasmic membranes. In numerous cells the cytoplasmic membranes formed the so-called undulating tubules which contained the VSV particles. The infected ependymal cells became necrotic and separated from the ventricular surface. The changes were similar in all three of the cerebral ventricles. At no time during the infection was the VSV observed near or within any of the choroid plexuses. Some ultrastructural changes, however, occurred in the choroidal epithelial cells. These may have developed either as a consequence of viral damage in the periventricular tissues, or due to virus presence in the cerebral ventricles.", "contents": "Ultrastructure of mouse periventricular and choroid plexus tissues in experimental vesicular stomatitis virus infection. The ultrastructure of the periventricular and choroid plexus tissues was studied in the three-week-old mouse, infected with the vesicular stomatitis virus (VSV) by the intranasal route. The VSV reached the periventricular ependymal lining late in infection. It was carried within the cytoplasm of myelinated axons and their sheath cells. Inflammatory cells, although few in numbers, may have also contributed to the virus dissemination. Once in the periventricular tissues the VSV entered the cells from the intercellular space. It replicated in both the ependymal and subependymal cells. It matured either directly in the cytoplasm, or by budding from the plasmalemma as well as the cytoplasmic membranes. In numerous cells the cytoplasmic membranes formed the so-called undulating tubules which contained the VSV particles. The infected ependymal cells became necrotic and separated from the ventricular surface. The changes were similar in all three of the cerebral ventricles. At no time during the infection was the VSV observed near or within any of the choroid plexuses. Some ultrastructural changes, however, occurred in the choroidal epithelial cells. These may have developed either as a consequence of viral damage in the periventricular tissues, or due to virus presence in the cerebral ventricles."} {"id": "PMID:183637", "title": "Late-infantile neuronal ceroid-lipofuscinosis. An ultrastructural study of lymphocyte inclusions.", "content": "Ultrastructural study of peripheral blood from two patients with late-infantile neuronal ceroid-lipofuscinosis with curvilinear bodies, demonstrated in brain biopsies revealed curvilinear bodies in lymphocytes. These findings indicate that ultrastructural investigation of circulating lymphocytes may be useful in the diagnosis of late-infantile neuronal ceroid-lipofuscinosis and may circumvent the need for brain biopsy. Curvilinear bodies were also present in the lymphocytes of a neurologically normal younger female sibling of patient 1, who has had a single seizure, leading to speculation that she may be in the early stages of the same disease. This case suggests the possibility of early detection of this disorder and indicates the importance of screening lymphocytes of siblings of affected patients. Tubular cytoplasm inclusions were present in a high percentage of lymphocytes of the asymptomatic parents and a younger sibling of these patients.", "contents": "Late-infantile neuronal ceroid-lipofuscinosis. An ultrastructural study of lymphocyte inclusions. Ultrastructural study of peripheral blood from two patients with late-infantile neuronal ceroid-lipofuscinosis with curvilinear bodies, demonstrated in brain biopsies revealed curvilinear bodies in lymphocytes. These findings indicate that ultrastructural investigation of circulating lymphocytes may be useful in the diagnosis of late-infantile neuronal ceroid-lipofuscinosis and may circumvent the need for brain biopsy. Curvilinear bodies were also present in the lymphocytes of a neurologically normal younger female sibling of patient 1, who has had a single seizure, leading to speculation that she may be in the early stages of the same disease. This case suggests the possibility of early detection of this disorder and indicates the importance of screening lymphocytes of siblings of affected patients. Tubular cytoplasm inclusions were present in a high percentage of lymphocytes of the asymptomatic parents and a younger sibling of these patients."} {"id": "PMID:183638", "title": "Suspected multiple primary tumors of the lacrimal and parotid glands.", "content": "A 63-year-old man had apparent primary tumors of the lacrimal and parotid glands. Initially an adenocarcinoma of ectopic lacrimal gland origin was suspected following biopsy of a mass in the left orbit. The patient received radiation therapy to this area and showed no recurrence of the original lesion or development of other tumors for a period of 27 months. At that time, the patient returned with a mass in the left preauricular area. This was surgically resected and found to be an adenocarcinoma of the left parotid gland. Both tumors were histologically similar, mucin-secreting adenocarcinomas. There has been no further evidence of tumor growth in an additional three-year period.", "contents": "Suspected multiple primary tumors of the lacrimal and parotid glands. A 63-year-old man had apparent primary tumors of the lacrimal and parotid glands. Initially an adenocarcinoma of ectopic lacrimal gland origin was suspected following biopsy of a mass in the left orbit. The patient received radiation therapy to this area and showed no recurrence of the original lesion or development of other tumors for a period of 27 months. At that time, the patient returned with a mass in the left preauricular area. This was surgically resected and found to be an adenocarcinoma of the left parotid gland. Both tumors were histologically similar, mucin-secreting adenocarcinomas. There has been no further evidence of tumor growth in an additional three-year period."} {"id": "PMID:183639", "title": "Occult tumors of the infratemporal fossa: report of seven cases appearing as preauricular facial pain.", "content": "Seven patients had occult malignant neoplasms either originating in or extending to the infratemporal fossa. Common symptoms were facial pain centered over the temporomandibular joint and facial numbness. These symptoms were sometimes associated with middle ear effusion and trismus. Multiple biopsies are often necessary to establish the diagnosis. The average delay in diagnosis from first symptom was 14 months. Infratemporal fossa neoplasia belongs in the differential diagnosis of facial pain.", "contents": "Occult tumors of the infratemporal fossa: report of seven cases appearing as preauricular facial pain. Seven patients had occult malignant neoplasms either originating in or extending to the infratemporal fossa. Common symptoms were facial pain centered over the temporomandibular joint and facial numbness. These symptoms were sometimes associated with middle ear effusion and trismus. Multiple biopsies are often necessary to establish the diagnosis. The average delay in diagnosis from first symptom was 14 months. Infratemporal fossa neoplasia belongs in the differential diagnosis of facial pain."} {"id": "PMID:183640", "title": "Hereditary deafness and sensory radicular neuropathy.", "content": "We report a case of radicular sensory neuropathy and deafness. The patients appears to be one of a family in whom several members were similarly afflicted. Thus, this case fits the pattern of hereditary deafness and sensory radicular neuropathy, originally described by Hicks in 1922.", "contents": "Hereditary deafness and sensory radicular neuropathy. We report a case of radicular sensory neuropathy and deafness. The patients appears to be one of a family in whom several members were similarly afflicted. Thus, this case fits the pattern of hereditary deafness and sensory radicular neuropathy, originally described by Hicks in 1922."} {"id": "PMID:183644", "title": "Equine herpesviruses. 6. Sequential infection of horses with types 2, 3 and 1.", "content": "The immunological and virological status of 3 foals in respect of equine herpesviruses (EHV) was established and the foals were sequentially infected with EHV2, EHV3 and EHV1. Following experimental infection with EHV2, no clinical signs of disease were observed in any foal. The inoculation of EHV3 into the genital tract resulted in lesions of the mucous membrane and perineal skin that were considered typical of equine coital exanthema. Following intransal inoculation of EHV3 extensive ulceration and pustule formation on the nasal mucosa was observed by day 5 accompanied at day 7 by a profuse, mucopurulent nasal discharge; on day 8 pustular lesions of the skin about the external nares appeared. Signs of disease after inoculation with EHV1 were milder than expected in 2 of the 3 foals. The possibility that recent, prior infection with EHV2 and/or 3 may protect against EHV1 was considered.", "contents": "Equine herpesviruses. 6. Sequential infection of horses with types 2, 3 and 1. The immunological and virological status of 3 foals in respect of equine herpesviruses (EHV) was established and the foals were sequentially infected with EHV2, EHV3 and EHV1. Following experimental infection with EHV2, no clinical signs of disease were observed in any foal. The inoculation of EHV3 into the genital tract resulted in lesions of the mucous membrane and perineal skin that were considered typical of equine coital exanthema. Following intransal inoculation of EHV3 extensive ulceration and pustule formation on the nasal mucosa was observed by day 5 accompanied at day 7 by a profuse, mucopurulent nasal discharge; on day 8 pustular lesions of the skin about the external nares appeared. Signs of disease after inoculation with EHV1 were milder than expected in 2 of the 3 foals. The possibility that recent, prior infection with EHV2 and/or 3 may protect against EHV1 was considered."} {"id": "PMID:183645", "title": "Duck viral enteritis: a comparison of replication by CCL-141 and primary cultures of duck embryo fibroblasts.", "content": "Cultures of primary cells and a line of fibroblast-like cells from the Pekin duck were both compared for their replication of the herpesvirus of duck viral enteritis. The two kinds of cells were equally accurate for quantifying virus upon isolation. Also, one-step growth curves showed that in both kinds of cultures new virus appeared by the 18th hour and that infectivity peaked at about 36 hours. Primary cultures yielded about 5.6 times as much virus as did the cell line, though plaques were more easily discerned in the latter. Because of availability, uniformity, and their known health history, CCL-141 cells offer some advantages for work with the agent of duck viral enteritis.", "contents": "Duck viral enteritis: a comparison of replication by CCL-141 and primary cultures of duck embryo fibroblasts. Cultures of primary cells and a line of fibroblast-like cells from the Pekin duck were both compared for their replication of the herpesvirus of duck viral enteritis. The two kinds of cells were equally accurate for quantifying virus upon isolation. Also, one-step growth curves showed that in both kinds of cultures new virus appeared by the 18th hour and that infectivity peaked at about 36 hours. Primary cultures yielded about 5.6 times as much virus as did the cell line, though plaques were more easily discerned in the latter. Because of availability, uniformity, and their known health history, CCL-141 cells offer some advantages for work with the agent of duck viral enteritis."} {"id": "PMID:183646", "title": "Spleen lesions of hemorrhagic enteritis of turkeys.", "content": "Spleens from turkeys were examined at intervals after intravenous inoculation with hemorrhagic enteritis virus. Spleen size increased until the 4th day after inoculation. On the 5th day, spleen size was markedly reduced and continued to approach normal size. Hemorrhagic enteritis antigen reached a peak concentration on the 2nd day, was reduced in concentration on the 3rd day, and was absent by the 4th day. Hemorrhagic enteritis precipitin antibody was present in all serum samples taken after the 10th day. Necrosis of lymphoid cells in the white pulp was prominent in the 1st day. Proliferation of immature-appearing cells on the 2nd, 3rd, and 4th days coincided with a lower virus antigen content in the spleen. Massive disintegration of the white pulp, associated with the appearance of small dense-staining lymphocytes, began on the 4th day. By the 5th day only the splenic arteries and the surrounding reticular cells remained. Restoration of normal-appearing white pulp was completed by the 8th day. No correlation was noted between splenic lesions and intestinal lesions. Many stages in the development of typical intranuclear inclusions were observed.", "contents": "Spleen lesions of hemorrhagic enteritis of turkeys. Spleens from turkeys were examined at intervals after intravenous inoculation with hemorrhagic enteritis virus. Spleen size increased until the 4th day after inoculation. On the 5th day, spleen size was markedly reduced and continued to approach normal size. Hemorrhagic enteritis antigen reached a peak concentration on the 2nd day, was reduced in concentration on the 3rd day, and was absent by the 4th day. Hemorrhagic enteritis precipitin antibody was present in all serum samples taken after the 10th day. Necrosis of lymphoid cells in the white pulp was prominent in the 1st day. Proliferation of immature-appearing cells on the 2nd, 3rd, and 4th days coincided with a lower virus antigen content in the spleen. Massive disintegration of the white pulp, associated with the appearance of small dense-staining lymphocytes, began on the 4th day. By the 5th day only the splenic arteries and the surrounding reticular cells remained. Restoration of normal-appearing white pulp was completed by the 8th day. No correlation was noted between splenic lesions and intestinal lesions. Many stages in the development of typical intranuclear inclusions were observed."} {"id": "PMID:183647", "title": "Role of the bursa of Fabricius in the pathogenicity of inclusion body hepatitis and infectious bursal disease viruses.", "content": "Chickens were chemically bursectomized with cyclophosphamide at 3 days old, and studies made of the effects of infection by inclusion body hepatitis virus (IBHV) and infectious bursal disease virus. In another experiment, 3-week-old chickens were infected with infectious bursal disease virus before inoculation with IBHV. Interference with the bursa of Fabricius by cyclophosphamide or by infectious bursal disease virus enhanced the pathogenicity of IBHV. In contrast, cyclophosphamide effects on the bursa protected chickens against infectious bursal disease.", "contents": "Role of the bursa of Fabricius in the pathogenicity of inclusion body hepatitis and infectious bursal disease viruses. Chickens were chemically bursectomized with cyclophosphamide at 3 days old, and studies made of the effects of infection by inclusion body hepatitis virus (IBHV) and infectious bursal disease virus. In another experiment, 3-week-old chickens were infected with infectious bursal disease virus before inoculation with IBHV. Interference with the bursa of Fabricius by cyclophosphamide or by infectious bursal disease virus enhanced the pathogenicity of IBHV. In contrast, cyclophosphamide effects on the bursa protected chickens against infectious bursal disease."} {"id": "PMID:183648", "title": "Serologic differences between strains of infectious bronchitis virus from New Zealand, Australia, and the United States.", "content": "The antigenic relationships of strains of infectious bronchitis virus from New Zealand, Australia, and the United States were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. The four previously described New Zealand serotypes were antigenically distinct from all the other strains tested.", "contents": "Serologic differences between strains of infectious bronchitis virus from New Zealand, Australia, and the United States. The antigenic relationships of strains of infectious bronchitis virus from New Zealand, Australia, and the United States were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. The four previously described New Zealand serotypes were antigenically distinct from all the other strains tested."} {"id": "PMID:183649", "title": "Electron-microscope studies on the pathogenesis of infectious bursal disease after intrabursal application of the causal virus.", "content": "Intrabursal application of infectious bursal disease virus (IBDV) is of advantage in studying sequential morphological events since the time of infection of the bursa is exactly known. A highly pathogenic strain caused first clinical symptoms 12 hr postinfection (PI) and death 24-30 hr PI. These are respectively 12 and 18 hr earlier than after per-oral infection. Numerous virus particles 53-58 nm in size, arrayed in a crystalline pattern and not surrounded by a membrane, are first found 6 hr PI in the cytoplasm of normal-looking lymphoid cells and macrophages. Some of the particles are less electron-dense and obviously immature; others have no core and therefore are regarded as incomplete. However, there is no evidence for the presence of more than one type of virus particle. Seven hr PI a membrane to segregate the virus clusters is formed, finally leading to autophagic vacuoles containing virus particles and cellular remnants. Within these vacuoles virus degradation takes part, though most of the infected cells, particularly the lymphoid cells, undergo cellular lysis, release the virions, and spread the infection to other cells of the bursa. At 18 hr PI the follicles are almost depleted of lymphoid cells. The findings show that early replication of IBDV is in the lymphoid cells and macrophages. These cells represent the main areas of virus multiplication, but the virions also can replicate in heterophils, reticulum cells, and reticular epithelial cells of the bursa.", "contents": "Electron-microscope studies on the pathogenesis of infectious bursal disease after intrabursal application of the causal virus. Intrabursal application of infectious bursal disease virus (IBDV) is of advantage in studying sequential morphological events since the time of infection of the bursa is exactly known. A highly pathogenic strain caused first clinical symptoms 12 hr postinfection (PI) and death 24-30 hr PI. These are respectively 12 and 18 hr earlier than after per-oral infection. Numerous virus particles 53-58 nm in size, arrayed in a crystalline pattern and not surrounded by a membrane, are first found 6 hr PI in the cytoplasm of normal-looking lymphoid cells and macrophages. Some of the particles are less electron-dense and obviously immature; others have no core and therefore are regarded as incomplete. However, there is no evidence for the presence of more than one type of virus particle. Seven hr PI a membrane to segregate the virus clusters is formed, finally leading to autophagic vacuoles containing virus particles and cellular remnants. Within these vacuoles virus degradation takes part, though most of the infected cells, particularly the lymphoid cells, undergo cellular lysis, release the virions, and spread the infection to other cells of the bursa. At 18 hr PI the follicles are almost depleted of lymphoid cells. The findings show that early replication of IBDV is in the lymphoid cells and macrophages. These cells represent the main areas of virus multiplication, but the virions also can replicate in heterophils, reticulum cells, and reticular epithelial cells of the bursa."} {"id": "PMID:183650", "title": "Marek's disease vaccine breaks: differences in viremia of vaccinated chickens between those with and without Marek's disease.", "content": "Viremia with turkey herpesvirus (HVT) and/or Marek's disease (MD) herpesvirus (MDHV) was examined in chickens from three different commercial flocks experiencing \"vaccine breaks\" following vaccination with HVT vaccine against MD. In all groups of sample chickens from the flocks, the incidence of detectable HVT viremia was significantly less in the MD-affected than in the healthy penmates, and incidence of MD was significantly higher in the birds without detectable HVT viremia than in the viremic penmates. The results suggest an association between HVT viremia and protection against MD development.", "contents": "Marek's disease vaccine breaks: differences in viremia of vaccinated chickens between those with and without Marek's disease. Viremia with turkey herpesvirus (HVT) and/or Marek's disease (MD) herpesvirus (MDHV) was examined in chickens from three different commercial flocks experiencing \"vaccine breaks\" following vaccination with HVT vaccine against MD. In all groups of sample chickens from the flocks, the incidence of detectable HVT viremia was significantly less in the MD-affected than in the healthy penmates, and incidence of MD was significantly higher in the birds without detectable HVT viremia than in the viremic penmates. The results suggest an association between HVT viremia and protection against MD development."} {"id": "PMID:183651", "title": "Effect of infectious bursal agent on the response of chickens to Newcastle disease and Marek's disease vaccination.", "content": "White Leghorn chickens raised from one day old in an environment contaminated by the infectious bursal agent (IBA) had lower geometric mean titers (GMT) as measured by the hemagglutination-inhibition (HI) test to the Newcastle disease virus (NDV), than control Leghorns reared in an uncontaminated environment. Immunosuppression, defined as a reduction in GMT, was most pronounced at 35-56 days old for Leghorns vaccinated with NDV at 1 and 28 days or at 28 days. In a separate trial with broilers, immunosuppression was similar at 42-56 days old. This study also demonstrated that IBA infection in chickens increased susceptibility to Marek's disease (MD). The unvaccinated control chickens infected with IBA averaged 56.3% MD lesions, whereas unvaccinated controls not exposed to IBA averaged only 18.1% macroscopic lesions. It was also found that 20.7% of the HVT-vaccinated chickens exposed to IBA had gross MD lesions, whereas those HVT-vaccinated chickens reared in an environment free of IBA had 2.99% gross MD lesions.", "contents": "Effect of infectious bursal agent on the response of chickens to Newcastle disease and Marek's disease vaccination. White Leghorn chickens raised from one day old in an environment contaminated by the infectious bursal agent (IBA) had lower geometric mean titers (GMT) as measured by the hemagglutination-inhibition (HI) test to the Newcastle disease virus (NDV), than control Leghorns reared in an uncontaminated environment. Immunosuppression, defined as a reduction in GMT, was most pronounced at 35-56 days old for Leghorns vaccinated with NDV at 1 and 28 days or at 28 days. In a separate trial with broilers, immunosuppression was similar at 42-56 days old. This study also demonstrated that IBA infection in chickens increased susceptibility to Marek's disease (MD). The unvaccinated control chickens infected with IBA averaged 56.3% MD lesions, whereas unvaccinated controls not exposed to IBA averaged only 18.1% macroscopic lesions. It was also found that 20.7% of the HVT-vaccinated chickens exposed to IBA had gross MD lesions, whereas those HVT-vaccinated chickens reared in an environment free of IBA had 2.99% gross MD lesions."} {"id": "PMID:183652", "title": "Isolation of infectious bronchitis virus from broiler chickens in Chile.", "content": "An infectious-bronchitis-like virus was isolated from 6-week-old broiler chickens unvaccinated with infectious bronchitis virus (IBV). The isolate produced lesions in embryonating chicken eggs (ECE) and clinical signs in birds characteristic of IBV. Serum-neutralization and agar-gel diffusion tests demonstrated the serological relationship of this isolate to IBV.", "contents": "Isolation of infectious bronchitis virus from broiler chickens in Chile. An infectious-bronchitis-like virus was isolated from 6-week-old broiler chickens unvaccinated with infectious bronchitis virus (IBV). The isolate produced lesions in embryonating chicken eggs (ECE) and clinical signs in birds characteristic of IBV. Serum-neutralization and agar-gel diffusion tests demonstrated the serological relationship of this isolate to IBV."}